THE LIBRARY OF THE UNIVERSITY OF CALIFORNIA LOS ANGELES GIFT DR. EMIL BOGEN Vh The Ransohoff Memorial Volume A Collection of Papers Representing Original Contributions to the Art and Science of Medicine by Colleagues and Students of DR. JOSEPH RANSOHOFF, M.D.. F.R.C.S. (Eng.l. F.A.C.S.. LL.D. WB ^/73 Nna #alutamua Hoh Sprfnliaaimp iMnrtuna AETERLINCK, in one of his most inspired plays, has originated a very beautiful conception of the hereafter. He believes that far away in the Realms of the Infinite, a man's spirit lives again each time that his name is recalled or spoken here below. Man's immortality rests upon the memories of him that linger m the thoughts of men. If there be truth in this answer to the greatest of all questions, then the spirit of the man in whose honor this book has been written, will live on in the golden sunlight of the great love that he left in the hearts of his fellow-men. There was about him a singular magnetism, a quality of lovableness that was irresistible. Men talked to him, told him their thoughts and he listened, and when they left him, although he had made no effort, they felt they had won a new and very valuable friendship. He had a deep, warm love for humanity, and each man's life and each man's happiness was worth his own personal effort to guard against harm. Though for over four decades he practiced surgery, he never became callous to the sight of human suffering. He believed that the highest duty of the doctor was to alleviate pain. With countless hundreds he walked through the Valley of the Shadow of Death and when he emerged with them into the glory of the sunshine once more, he had their lasting confi- dence and friendship. He will live in the thoughts of these people as he was to them in their hour of trial, the healer and the friend. He loved youth and the wholesome out-of-door pleasures of youth. His happiest summers were passed with a band of young men in the Canadian woods, where he tramped and fished and smoked and read and cooked marvelous hsh chowders for an enthusiastic group of hungry young- sters. To watch him hook and play and land a huge "musky " with those delicate surgeon's hands of his was a treat for a true sportsman. And because he knew and loved and understood the ways of youth he was able to impart to young men the difficult art of his beloved profession as few- have been able to teach it. His bedside clinics were invested with a flash of genius. His teachings meant more to his pupils than the dry accumula- tion of facts necessary to pass examinations and make a livelihood. They meant the handing on of a sacred trust from the old generations to the new. So he will live in the hearts of the men he taught, revered by them as the great teacher who loved and understood them. In the store-house of his mind lingered fragments and bits of prayers from the old, old faith of his forefathers. Many an old patriarch with sorrow-clouded eyes, lying lonely and suffering in the wards, would brighten into happiness when this man, in passing his bed, would stop to wish him well or whisper a time-worn phrase in the dialect of his own people. He loved the beautiful things of life, books, music, nature. But, above all else, he loved with a fierce intensity the work to which he devoted the years and strength of his manhood. Before he died, he, who had given the world so much, said: "I have had a perfect life; the world owes me nothing. " When he died the highest and the most obscure sent messages telling of the loss they had sustained in his passing. He had a great mind and a gentle soul. The world is richer for his having lived. (Eantents PAGE Nos Salutamus Vos Recentissime Mortiios iii Editor's Preface vii Dr. Joseph Ransohoff 1 Publications of Dr. Joseph Ransohoff 7 Elmer R. Arn : The Therapeutic Possibilities of Blood Transfusion — Methods, Indications and Results 13 Albert J. Bell : Observations Upon Scarlet Fever, Diphtheria and Measles at the Cincinnati Contagious Hospital 23 Julien E. Benjamin and Sidney Lange : Report of Nineteen Cases of Hyperplasia of the Thymus Gland Treated by the X-Rays 36 Oscar Berghausen and Chas. E. Howard : The Treatment of Wounds, vi'ith Reference to Tetanus Prophylaxis 42 Kenneth D. Blackfan : The Early Recognition of Hydroceplialus in Aleningitis 4C> George Emerson Brewer : Standards of Success in Medicine 5(5 Mark A. Brown : Multiple Infections 64 Robert B. Cofield : Disinfection of the Knee Joint 71 George W. Crile : The Mechanism of Shock and Exhaustion 75 Joseph L. DeCourcy : Thyroidectony— A Brief Review of 137 Cases 91 Albert Faller: Sources of Wassermann Error and Their Control 96 Leonard Freeman : Primitive Surgery of the Western Hemisphere 101 Albert H. Freiberg : Wolff's Law and the Functional Pathogenesis of Deformity 114 Alfred Friedlander and Carey P. McCord : The Atropin Test in the Diagnosis of Typhoid Infections 129 Alfred Friedlander and J. Victor Greenep.aum : Note on the Influence'of Food Upon the Intestinal Flora of Infants 136 W. D. Haines : Tumors of the Mediastinum 144 William S. Halsted : A Striking Elevation of the Temperature of the Hand and Forearm Following the Excision of a Subclavian Aneurism and Ligations of the Left Subclavian and Axillary Arteries 150 Meyer L. Heidingsfeld : The Pathology of Chromidrosis 161 Harry H. Hines : Brain Decompression Operations 171 Christian R. Holmes: Hospitals — History of Their Development 175 Herman H. Hoppe: i. The Medical Treatment of Graves' Disease with Special Reference to the Use of Corpus Luteuin Extract 186 ii. The Treatment of Hyperthyroidism with Corpus Luteum 193 CONTENTS— Continued. PAGE Samuel Ici.auer: i. The X-Ray Examination of tlic Mastoid Region 202 ii. The Clinical Value of Radiography of the Mastoid Region 211 Raphael Isaacs : The Structure and Mechanics of Developing Connective Tissue 217 Dennis E. Jackson and Gerard Raap : An Experimental Investigation of Certain Features of the Pliarmacological Action of Salvarsan 237 Howard A. Kelly : A Case of Cancer of the Vagina, Cervix and Body of the Uterus, Treated by Radium 254 Thomas H. Kelly and Hiram B. Weiss : The Diagnosis and Treatment of Diaphragmatic Pleurisy 258 Henry McE. Knower : Demonstration of the Interventricular Muscle Bands of the Adult Human Heart 3G7 George H. Kress : Ocular Angio-sclerosis 268 Frank W. Langdon : Biologic Aspects of Dementia Praecox 275 Louis A. Lurie : Pernicious Anaemia with Mental Symptoms 286 Benj. F. Lyle : The Tuberculosis Problem in Cincinnati 322 Merrick F. McCarthy : Dizziness 316 Carey Pratt McCord : The Pineal Gland 355 Edward F. Malone : The Nucleus Cardiacus Nervi Vagi and the Three Distinct Types of Nerve Cells which Innervate the Three Different Types of Muscle' 308 Edward C. Mason and Carl E. Pieck : A Pharmacological Study of Benzyl Benzoate 374 William J. Mayo : Relation of the Development of the Gastro-Intestinal Tract to Abdominal Surgery 391 Willy Meyer : The Necessity for the Application of Differential Air-Pressure in Thoracic Operations 402 Roger S. Morris : Blood Formation in the Liver and Spleen in Experimental Anaemia 412 A. J. Ochsner and D. W. Crile: Clinical Consideration of Osteomyelitis 420 Wade W. Oliver : A Rapid Method of Pneumococcus Typing 445 Dudley W. Palmer : Hyperplastic Pyloric Stenosis of Infancy 449 J. Edward Pirirung : Complications and End Results of Bile Duct Infection 455 Benjamin Knox Rachford : The Influence of Bile on the Fat-Splitting Properties of Pancreatic Juice 401 J. Louis Ransohoff: Adherent Hernias of the Large Intestine 480 William Ravine: The Dangers and Fallacies of Intraspinous Injection of Salvarsan 493 CONTENTS— Continued. PACE Augustus Ravogli : On the Strictures of the Male Urethra 501 Moses Salzer : A Case of Tin Poisoning 511 M. G. Seelig : Rhinophyma 514 E. Otis Smith : Anatomy and Pathology of the Seminal Vesicles 520 Chas. T. Souther: Inguinal Hernia 528 Robert W. Stewart : Toxicity of Urine in Pregnancy 540 Elmore B. Tauber: The Early Diagnosis of Syphilis : . 549 William B. Wherrv and C. T. Butterfield : Inhalation Experiments on Influenza and Pneumonia, and on the Importance of Spray-Borne Bacteria in Respiratory Infections .555 Hiram B. Weiss: The Principles and Treatment in Mercuric Chloride Poisoning 504 Philip Zenner : The Venereal Problem 509 iEJiitnra' Prrfarr N an effort to express to Dr. Joseph Ransohoff their appreciation of his place m the science and art of Medicine a group of his former students determined to issue a volume containing papers consisting of original contributions to the advancement of Medicine by his students and colleagues. This was in June, 1920. The death of Dr. Ransohoff prevented the presentation of this book to him personally, but the publication was continued as a Memorial Volume. The Editors wish to express their appreciation to the many friends of Dr. Ransohoff for the help they have given in making this work a reality, and to the S. Rosenthal & Co. for their part in the printing of this book. Recognition is given to the publishers of the different articles for permission to reprint them in this book. EDITORIAL BOARD Dr. A. C. Bachmeyer Dr. J. C. Oliver Dr. Julien Benjamin Dr. B. K. Rachford Dr. Nora Crotty Dr. Samuel Rothenberg Dr. Martin H. Fischer Dr. Robert Sattler Dr. Frederick C. Hicks Dr. E. O. Smith Dr. Carl HiUer Dr. Robert Stewart Dr. Raphael Isaacs Dr. Wm. B. Wherry Dr. Albert Mathews ®fl ir. 3lnBrpI| SatiHnlinff Anatomist, .burgeon, v^chnlar, iM-itiul and 'readier; to you is dedicated this book. Ikil abo\e all to ycui as teaclier. P'niinent in all of your under- takings, as teacher have you been pre-eminent, and the men who throughou' forty-two years have known you thus, inscribe to you this tribute of af- fection and of homage. Friend and Teacher: the hope had been cherished to i)resent to \ou this enduring token, while your eye was still undimmed a)id your tongue stil! able to serve in its way, inimitable. Within a few short months Fate ha,- taken from us this great privilege. To the wreath of immortality whicli you have woven for yourself m.ny we be permitted to add a few leaves. "Memory is a net; one finds it full df tish when he takes it from the brook; but a dozen miles of water ha\c run through it without sticking." There- fore, let us, your friends and jjupils, wander gently through the years which you have s])ent, that for us and those who come after us they may have an imperishable record. For sixty years has stood the church of the Franciscan Fathers in Cin- cinnati. For sixty years has the grimy figure of St. Francis of Assisi looked down upon Liberty street ; venerated by many devout passersby, but also the butt of many a jest from the mischievous boys, who, throughout many years, found in the narrow street below their only playground. To the east a garden, closed in by a high brick wall, separates the church from Vine street ; even now, after the passing of two generations of men, a fairly busy thoroughfare, it was formerly very dififerent in its aspect. Abounding in many small shops, the street is, in the daylight hours, perhaps not greatly changed in appearance. The dethronement of King Gambrinus has, how- ever, played havoc with its nocturnal glory. Here we are almost at the northern terminus of that region for so many years gaily spoken of a; "Over the Rhine." And it was so spoken of not merely in gayety, but also most aptly ; in its houses and in those of the contiguous streets lived a populace prevailingly German. Few, indeed, were the persons one might have encountered here sixty years ago who would have failed to compre- hend a (German salutation, and fewer still. Ibosr wli,, would have failed lo resiiond to it politely and respectfully. In place of the brilliant electric il- RAXSOHOFF MFMOR/.iL VOLUME lumination of our time, emphasized by the gaudy resplendence of the "movies" found in every block, we would have found only flickering gas lamps. The many "Bierstuben" with which the street abounded were, for the most part, lighted with oil lamps, and the evening found their tables bearing many glasses of foaming "Lager," behind which sat decent, thrifty and sober men who had wandered from the "Fatherland" long before it went mad with war lust. Some of them, indeed, were forty-eighters. who sought this country in search of liberty and opportunity, and found both. If our imaginations carry us into these rooms with ears as well as eyes, we shall hear serious talk ; in this year of 1860 was Abraham Lincoln ele- vated to his troublous eminence and the premonitions of the Civil War were in the minds and the mouths of men. Then, from the houses of German \'ine street and the many habitations of the neighborhood went forth hun- dreds of these "German citizens" and their sons to prove with their blood and their lives how real was their allegiance to the Union; just as the sons and the grandsons of these same men have not hesitated to show it again in our day in a manner more telling. For now the enemy had become the same "Fatherland" whence their forebears had been derived. The church of St. Francis is not a beautiful edifice; quite the contrary. From a facade severely plain there rise two spires, as were there two routes to the empyrean; for if the unmoving hands of the clock in the on?^ are at a quarter before five, those of the other say that it is half past eleven. The western windows of the church give upon a narrow street, called ISremen street until 1918. Then in the spirit of belligerent patriotism the name was changed to the present, Republic street. In an unpretentious brick house on Bremen street, just north of St. Francis Church, lived Xathau Ransohoflf, and here was spent the boyhood and youth of his only son and yoimgest child. Joseph. Nathan Ransohoff came to Cincinnati, almost one liundred years before these lines were written, from Westphalia, where in his family there had been men of culture. If great fame was not theirs, neither were they without local distinction, and a prized possession of Joseph Ransohofif's was the portrait of his uncle, with a decoration upon his breast in token of his successful work among the people with whom he lived. It is interesting that the stranger to this city found here friends in the persons of Jacob and Sarah Workum, natives of Amsterdam, the maternal grandparents of Minnie Workum Freiberg, who many years after- ward became Mrs. Josejih Ransohoff. Folk of a pious Jewish orthodoxy were Nathan and Esther Ransohoff. Content with the modest mercantile success which had come to them, they were also satisfied to live quietly in the shadow of St. Francis Church, with its mute and unintentional suggestion that there is more than one way to that realm which, for mortals, is impenetrable and unknowable. Here l)layed the boy. "the hope of the name." He had been intended for the rabbinate by his parents, and with this in view there was laid the foundation Page 2 DR. JOSEPH RANSOHOFF for extended training in Hebrew lore and tradition which had an effect upon his mind and character, enduring to the last and which often occasioned surprise to those who were themselves thus learned. The public school of the neighborhood and Woodward High School gave him all that he received of systematic secular training. After his graduation from high school, in 1870, he passed directly into the study of medicine. The Medical College of Ohio, from which he was graduated in 1874, was one of the best known medical schools of the country of that day, as well as one of the largest. Graham, Blackman, M. B. Wright, Reamy and Bartholow, these were the men who inspired the young medical student with high ideals of medical pedagogy and of scholarship. Of these none exercised a more potent and lasting influence than Graham, and I have heard Ransohoff say, more than once, that in all of his student wanderings he had met with nt more brilliant or gifted teacher; his style of teaching he characterized as "histrionic." In my mind's eye I see the father Ransohoff returning to his simple home from the synagogue on the Sabbath eve (Friday) of February 27, 1874. I see him celeljrating the Sabbath meal in its traditional beauty : I see the family walking the long way down \'ine street to Fourth ; I see them seated in Pike's Opera House, where the commencement exercises of the Medical College of Ohio were held. But above all, I see the pridj in the faces of mother and father as they see their son, the youngest of the class, called forth to receive the gold medal from the hand of Thaddeus A. Reamy for his essay on Puerperal Eclampsia. How singular, perhaps in no branch of his profession was he afterward destined to have a less active interest than in obstetrics. Before his graduation he had already served as intern in the Cincinnati Hospital ; he has told me that the degree of M. D. was conferred only after the year of internship in order to hold the young men in the hospital. The food was so poor that defections before the end of the term could not be otherwise prevented. After his graduation he proceeded to Germany for graduate study, and it was his father's wish that he should obtain a European degree. Wurz- burg, Berlin, \ienna, Paris and London, these were the places of abode and earnest study until his return to Cincinnati in 1877. Kolliker, \'irchow Langenbeck, Billroth, Tillaux, Paget and Jonathan Hutchinson ; Hebra, Rokitansky and Gerhardt, these are the names of men often spoken of by Ransohoff by reason of the influence which they had exerted upon his de- velopment, both as practitioner and as teacher. Having proceeded to Lon- don, Ransohoff applied himself energetically to preparation for the exam- ination for Membership of the Royal College of Surgeons of England. This was the degree which he hoped to bring back in response to his father's wish. The difficulty lay chiefly in extremely rigid tests in anatomy: the Fellowship degree seemed altogether beyond jjossibility in its demand for the utmost in the way of anatomical and surgical knowledge. It was practically never taken until at least one year after the Membership had been conferred, and it seemed time to return to America and to take up KAXSOnOFF MEMORIAL VOLUME the pursuit of the practice for which he had been so long and so arduously preparintj. The M. R. C. S. was given him in April, 1877. Some days afterward, while working in the wonderful Hunterian Museum, he was recognized by Sir James Paget ; he complimented him upon his brilliant examination and urged him to try for the Fellowship. This resulted in his obtaining the greatly coveted F. R. C. S. in June. 1877, under conditions almo.st, if not altogether, unprecedented. Immediately thereafter RansohofY returned to Cincinnati. Heralded by this remarkable accomplishment, it was easy for him t.; obtain recognition in the Medical College of Ohio. Late in the summer of 1877 he was made Demonstrator of Anatomy and began to teach surgery in the college dispensary. In 1879, the untimely death of the brilliant Lan- don Longworth made a place for him as Professor of Descriptive Anatomy. Remarkable didactic talent such as Ranschoff possessed insured for him im- mediate advancement as the opportunities appeared. He soon was made a member of the staff of the Good Samaritan Hospital and began to hold surgical clinics, which were eagerly attended by the students, who were not long in appreciating his unusual ability as a teacher, even as the new- comer to a group made up of men like Dawson, Reamy, Conner. \\'hitta- ker and his. as well as our, lamented friend, Frederick Forchheimer. Since 1902 Ransohoiif occupied the Chair of Surgery in the Medical College of Ohio and in the University of Cincinnati, with the organization of a veritable university faculty in 1909. It was his privilege to li^■e to see the fulfillment of a prophecy which was made at this time by one who dis- believed in its probability, when he wrote : 'Tf the lessons of the recent past are heeded, if the ambition of ihe in- dixidual is tempered by love of science and by civic patriotism, if the uni: is willing to be absorbed by the totality of the purpose embodied in the whole, then Medical Cincinnati may rise again in all her old-time glory, an im- perishable monument to the great Daniel Drake, whose genius hovers about the old town, where \\'estern medicine was born and grew into a vigorous adolescence and heroic manhood." With the occupation of the new Cincinnati General Hospital came the opi^ortunity for the full flowering of the genius of Joseph Ransohofif as a teacher of clinical surgery, and the climax was reached with the installation of the Medical College in its jiresent magnificent building on the sam-^ grounds; it was now possible to do things for the student of medicine not dreamed of when he began his career as teacher. The opportunity which he now had for devoting a greater amount of time to teaching was seized with eagerness ; an eagerness which could not have been greater had it been the first chance of his life to show his ability and to establish his reputation. It were entirely fruitless to attempt the analysis of his success as a teacher. A sufficient explanation is found in his enthusiasm and in that of his students. That he had passed the time of life when teachers of medicine commonly relincinish a large part of their work, seeking greater Fayc i DR. JOSEPH RANSOHOFF leisure and relief from routine burdens, was never apparent to him in his own self -consciousness, I am sure. (3n the contrary, he shrank from the thought that he might live, being no longer a teacher of surgery. Xature had been very kind to Joseph Ransohoff, not only in giving him an active, clear-thinking brain and a remarkably retentive memory, but with these a pleasing voice, a charm of presence and, above all, a lov2 for what was fine and beautiful. The history of his profession and of the outstanding figures there to be found liad an irresistible lure for him ; he was therefore learned not only in the technical side of medicine and sur- gery, but also in the story of its development as art and science. His ad- dresses in this field were not many, but they were, all of them, notable an.J characterized by grace of diction and charm in the manner of their deliver}'. That he had both talent and love for literary effort not at all connected with his profession is not as well known as it should be. He wrote a num- ber of stories of distinct merit, but they were not published. Surely the crowning effort of his life, in its relation to the Medical College and to rhe public, was presented on that delightful November day of 1920, when there was celebrated the centennial of the medical school. Ransohoff's unbounded admiration for Daniel Drake, the great founder, and his personal love for Christian R. Holmes, the great builder, made easy for him the composition of his address, "Drake and Holmes," which completely captivated an audi- ence which overfilled the auditorium of the college building. This was for him a great day, not only in the personal triumph which he achieved, but because there was conferred upon him by his Alma Mater the degree of Doctor of Lav>-s. This was a reward, not too great, for more than fort\- years of devoted service of high value and conspicuous results. Aias ! thai it should also have marked his last appearance in that auditorium. It were superfluous to emphasize here in what high degree Ransohoff was a remarkable and successful practitioner of surgery. In addition t.i learning, manual dexterity, remarkable clinical judgment and even intuition, he had a grace of manner and a symjiathy for those who suffered, which endeared him to his patients, exceedingly. He came into surgery at t'lc beginning of its most active and fruitful ]:)eriod. Change followed upon change, innovation upon innovation, but Joseph Ransohoff was able to pass from the scenes of his labors after a long career of uninterrupted activity, conscious of the fact that he was always, and to the end, abreast of the times, marking with his own feet the forefront of progress. "-\nd tho', in tliis lean age forlorn, Too many a voice may cry- That man can have no after-morn, Not yet of these am I. The man remains, and vvhatso'er He wronght of good or Ijrave Will mould him thro' the cycle-year That dawns behind the grave." Fratcr, avc aUjiic 7'alc. ALBERT H. FREIBERG. ^ubliratinna of ir. DflBPjjI^ ?Rananl|off 1879 A Contribution to the St'.idy of the Operation for Hare Lip. ( Cin. Lancet-C'l 1879, V. :\ p. 1-3.) Tetanus; Nerve Stretching; Cure. (Cin. Lancet-Clinic. 1871), v. 2, p. 41-4:!.) Aneurism of the Innominate and .\orta; Ugature of the Carotid and Subclavian ,\rteries; Death on the Seventh Uav. ( .\ni. J. Med. Sc, IMSO, v. Xn, p. ;!."r2-.",il. ) Hernia of the .-XbduCor Lon.yi.:s. (Cm Lancet-Clinic, lst<0, v. 4, p. .jii.) 1881 Erysipelatous Inflammation of the Glottis. (Cin. Lancet-Clinic, 1881, n. s. v. 7, p. .M:'..) Permanent Perineal Fistula. (Cin. Lancet-Clinic, 1881, n. s. v. .) Rare Cases of Syphilis. (Cin. Lancet-Clinic. 1881, n. s. v. 7, p. !-l.) A Contribution to the Sur.«ery of the Liver. (Med. Rec. 1882, v. 22, p. 2")8-()l.) Ein Beitrag zur Chirurgie der Leber. (Berl. Klin. Wchnschr., 1882, v. 19, p. 600-003.) Fibroid Polypus of the Rectum. (Cin. Lancet-Clinic, 1882, n. s. v. 8, p. 486.) Gunshot Injury of the Shoulder. (Ciu- Lancet-Clinic, 1882, n. s. v. 8, p. l-t.) Tetanus from Injury by Toy Pistol; Stretching of the Median and Ulnar Nerves; Death. (Cin. Lancet-Clinic. 18,>^2. n. s. v. 9, p. 200.) 1883 [Discussion.] (Cin. Lancet-Clinic, 18.^:!, n. s. v. lo, p. 4!):..) Early Trephining in Diseases of Bones. (J. Am. Med. Ass., 1883, v. 1, p. 299-302.) Epithelioma of the Lips. (Cin. Lancet-Clinic, 1883, n. s. v. 10, p. 447-49.) Papilloma of the Bladder; Operation; Cure. (Med. News, Phila., 1883, v. 42, p. 1"):1-5C.) Retro-Peritoneal Cysto-Sarcoma. (Med. News, 1883, v. 43, p. .j7."i-77.) The Treatment of Empyema by Pleural Incision; Report of Three Cases. (Cin. Lancet-Clinic, 1883, n. s. v. 11, p. 431-.3.^.) 1884 Sanguineous Cyst of the Neck. (Cin. Lancet-Clinic, 1884, n. s. v. 13, p. 1-4.) 1885 Two Ovariotomies in the Same Patient. (Med. News, LSS.'i, v. 47, p. 11."j-19. .Also reprint.) Two Ovariotomies Successfully Performed on the .Same Patient. (Cin. Lancet-Clinic, 188.J, n. s. V. 14, p. :,m-'.n.) Urethral Calculi. (J. Am. Med. .Ass., 18)S.-,, v. 5, p. (I.V07.) Urethral Calculi. (Tr. Ohio Med. Soc, 188.-.. ,>. 1(19-73.) .\ Case of Aortic .'\neurism Treated by the Insertion of Wire. (J. .\m. Med. .\ss., 1880, V. 7, p. 481-8.-).) A Case of Aortic Aneurism Treated by the Insertion of Wire. (Med. News, Phila., 1886, V. 48, p. .597-602.) A Case of Aortic Aneurism Treated bj the Insertion of Wire. (Phila., 1880, 18p., 12°. [Repr. from Med. News, 188().l ) Tracheotomy; a Report of Nine Cases. (Med. & Surg. Reporter, 1880, v. 'A. p. 2Cll-(i2.) Tracheotomy in Diphtheritic Croup. (Lancet-Clinic, 1880, n. s. v. 10, p. 9.-|, disc, p. 1(17.) Page 7 RAXSOHOFF MEMORIAL VOLUME Considerations on the Anatomy, Physiology, and Pathology of tlie Caecnm and Appendix. (J. Am. Med. Ass., lf<88, v. 11, p. 40-46.) Gastro Enterostomy; a Clinical Lecture. (Polyclinic, 1889-90, v. li, p. -il'll-ll. ) Old Bilateral Dislocation of the Elbow, With Report of Two Cases. (Cin. Lancet- Clinic, 1889, n. s. y. I'.l, p. IJ-MC; also J. Xat. Ass. Railway Surg.. 1889, v. •_', p. 1-28-34.) 1890 Fractura Basis Cranii. (J. Med. Coll., Ohio, 1890, v. 1, p. 29.) Valedictory Address. (Lancet-Clinic, Mch. 8, 1890.) Rupture of Middle Meningeal Artery Without Fracture; Ligature of Common Carotid Artery for Secondary Hemorrhage. (Ann. Surg., 1890, v. 12, p. 110-24.) Rupture of Middle Meningeal .Artery Without Fracture; Ligature of Common Carotid Artery for Secondary Hemorrhage. ( Tr. .\m. Surg. .\ss., 1890, v. 8, p. 167-79.) Tuberculous Disease of the Tarsus. (J. Med. Coll. of Ohio, 1890, v. 1. p. 8.")-88.) Tuberculous Diseases of the Tarsus. (Med. News, Phila., 1890, y. .")7. p. ■■i(i4-(i7.) \'aginal Cystolithotomy in a Child. (J. Med. Coll., Ohio, 1890, v. 1, p. 41.) Abscess of Liver; Hepatotomy. (J. Med. Coll. of Ohio, 1890-91, v. 1, p. 111.) 1891 .Aneurism of the Femora! .Artery; Deligation of the Superficial Femoral; Cure. (J. Med. Coll. of Ohio. 1891, y. 2, p. -V Also Cin. Lancet-Clinic 1.891, v. 20, p. o29-;31.) Pistol-Shot Wounds of the Brain. (Cin. Lancet-Clinic, 1891. v. 27. p. .Vi7-(il.) Linear Craniotomy for Microcephalus. (Med. News, June 13, 1891.) Ruptur der .Arteria meningea media ohne Fractur; Ligatnr der Arteria carotis communis bei secundarer Blutung. (Arch. f. Klin. Chir., 1891, \-. 42, p. 229-:!0. ) 1892 Management of the Gangrenous Hernia. With Report of a Case. (.1. .Am. Med. .Ass., 1892, V. 19, p. 198.) Traumatic Aphasia. (Ohio Med. J., 1892. v. -i, p. 41-4:>.) Treatment of the Gangrenous Hernia. (.Ann. of Surg., 18!t2, v. lii, p. .'i.'ili-.Sl.) Trephining for Abscess of the Brain. (Cin. Lancet-Clinic. 1892. v. 29. p. Oilii-7:!.) 1893 Empyema. (Tr. Ohio Med. Soc. 189:'.. p. 28.-.-9:3. Also Cin. Lancet-Clinic, 189.1, v. 31. p. 150-.-,4.) Recurrent .Appendicitis; Laparotomy: Fecal Concretion, With Bullet for Xucleus. (Ohio Med. J., 1893. v. 4, p. 2:io.) Report of a Case of .Appendicitis. (Cin. Lancet-Clinic, 189:i, v. :>0, p. 07").) 1894 Extirpation of Aneurisms. (.Ann. of Surg., 1894. v. 19, p. 78-84.) Thyroid .Abscess, Thyroidectomy; Recovery. (.Ann. of Surg.. 1894, v. 2o, p. 4O0-41:!.) Strangulated Hernia Gangrene of the Intestine. (Ohio Med. J.. 1894, May.) Treatment of Strangulated Hernia. (J. Am. Med. Ass.. 1894, v. 23. p. 20-20.) 1895 Concerning Stone in the Kidney, and Its Operative Treatment. (J. .Am. Med. .Ass., !8!r,. V. 25, p. 1-7.) Injuries and Diseases of the Neck. (Encvcl. Sur.g. (.Ashhurst. N. Y.). 189."), v. 7, p. 7.M-82.) PUBLICATIONS OF DR. JOSEPH RANSOM OFF Nature and Treatment of Glands of the Neck. (Med. Fortnightly. 189.",, v. 8, p. 470.) Pelvic Reflexes in the Male. (Med. Prn-rcss, ISICi, v. 11. p. 'jni-(il,) Pelvic Reflexes in the Male. I .Am. j. ..I ()h^t., ls!i.-,, v. :11, ]). il7.-,-7!l.) Sarcoma of Bone. (Ohio Med. J.. ISii.',, v. (i, ii ■_'■> .'.ii. ) Tuberculosis of the Neck. (Ohio Medical Journal, IS!).",, p. 17l'-74.) 1896 Large Parosteal Fibro-Sarcoma of the Thigh. (.Annals of Surgery. ]8!l(i, v. 24, p. 188-195.) (Whitaker, Ransohoff and Kramer) ; Paraplegia : Gunshot Wound of the Spinal Cord ; Bullet Located by the Roentgen Ray, and Subsequently Extracted ; Obstinate Bed Sores Relieved by Constant Stay in the Water Bath for Three Months. (Inter. Med. Mag.. 189(i-7, v. .5, p. (347-(i(i8.) Parosteal Sarcoma of the Femur; Extirpation With Recovery. (Tr. Am. Surg. Ass., 189(1. V. 14, p. 44:!-4.-,4.) Susceptibility and Immunity to Surgical Infections. (Ohio Med. Journal. ]89li. v. 7, p. I(i9-172.) Surgical Treatment of Tubercular Lesion. (Cin. Lancet-Clinic, 189(1, v. 30, p. (\'i.\-i't'u .) Ueber Erinnerungstauschungen bei .\lkohol-Paralyse. (Allg. Zeitsrhr. f. Psychiat. etc., 189(;-7, p. 9:«-94:.!.) Operative Treatment of Irreducible Subcutaneous Fractures. (.Am. Jour. Med. Science, 1897, v. 114, p. 417-424.) 1897 Radical Cure Umbilical Hernia, by Omphalectomy, (Med. Rec, l.'>97, v. ."il, ji. I."i(l-."i2.) Remarks on Operative 4>eatment of Irreducible Dislocation (jf the Shoulder. (Ohio Med. lournal. Inne. ls!(7.) Cancer of the Bladder. (Cin. Lancet-Clinic, 189.S, n. s. v. 41. p. 0:!2.) Lympho-Sarcoma of the Neck. (Cin. Lancet-Clinic, 1898, n. s. v. 40, p. ()(I8-10.) Considerations on the Diagnosis and Operative Treatment of Gall Stones. (Cin. Lancet-Clinic. 189X. n, s, \-. 4i», p. 9-".-l(il.) 1899 Decortication of the Tongue, in the Treatment of Lingual Psoriasis. (.Ann. of Surgery, May, 18ft9.) Nephrectomy Versus Nephrotomy. (Tr. Am. Surg. ,\ss., 189!t. ) 1900 Our Students and Their Teachin.g. (Cin. Lancet-Clinic, 190(1. n. s. v. 44. p. 479-48(1.) Specimen of Vesical Calculus. ((I'in. Lancet-Clinic, 19(iii, n. s. v. 4-'i, ]). (!l."i-l(i.) 1902 Trephining for Brain Tumors; Report of Two Successful Cases, One of Nine Years. (J. of Am. Med. Ass,. 19(12. v. :!9, p. 9(1:1-0(1.) 1903 (Ransohoff, J., and Phelps, A. V.) : An Unusual and Fatal Hemorrhage from Trephining. (Tr. Am. Surg. Ass., 190.^, V. 21, p. 563-568.) Zur Aetiologie der akuten hamorrhagischen Encephalitis. (Monatsch. f. Psychiat. u. Neurol., 190.. n. s. v. -A, p. .j.-)8.) Thyroidectiimy in the Treatment of Exophthalmic Goitre: With Report of Cases. (Lancet-Clinic, 19ii.-|. n. s. v. •->4, p. 07:5-78.) 1906 Cancer of the Stomach from the Surgeon's \'ievvpoint. ( Lancet-Clinic, 19ii(i, n. s. v. .".(^ p. 0-2.-.---'9.) Case of Sarcoma of Head of the Tibia. (Lancet-Clinic, 1900, n. s. v. -Mi, p. 69^..) Discussion of the Pleura in the Treatment of Chronic Empyema. (Ann. Surg.. 1900, V. 4:3, p. 502-11.) Cancer of the Stomach from the Surgeon's Viewpoint. (Abstr. Ohio Med. J., 1906-7, V. 2, p. l(i2-0.-,. ) Gangrene of the Gall Bladder. (Tr. South. Surg. & Gynec. Ass.. i;)o.-.; Phila., 1900, V. 18, p. 48-68.) Gangrene of the Gall Bladder, Rupture of the Conuuon Bile Duct. With a Xew Sign. (J. Am. M. Ass., 1906, v. 4(1, p. :M5-97.) Pulsating Exophthalmos; Ligature of the Common Carotid, External Carotid and Superior Thyroid Arteries. (Surg. Gynec. & Obst., 1906, v. '■'>, p. 19:!-9.->.) Rupture of the Common Duct With an Unusual Sign. (Tr. South. Surg. & Gynec. Ass., 1905 ; Phila., 1906, v. 18, p. .50-68.) The Treatment of Fractures of the Patella. (J. .\m. ^L .Ass., l»0(i, v. 47, p. 1177-81.) 1907 Die Behandlung der Patellarbruche. (Klin. Therap. Wchnschr., 1907, v. 14, p. 127-36.) Cirrhotic Liver, With -Ascites and .Albuminuria ; Talma Operation Performed, Fol- lowed bv Relief of .Ascites and Albuminuria. (Lancet-Clinic, 1907, n. s. v. 58, p. 3.55.) ■ Very Large Recurrences .After Operation for Carcinoma of the Breast. (.Ami. Surg., 1907, V. 46, p. 72-80.) Very Late Recurrences .After Operation for Carcinoma of the Breast. ( Tr. .Am.' Surg. Ass., 19(17, v. 25, p. 187-95.) 1908 A New and Rapid Method of Perineal Drainage in Suprapubic Prostatectomv. (J. Am. M. Ass., 1908. V. 51, p. 887-9(i. ) Surgery of the Kidney, the Ureter and the Suprarenal Glan, p. 320; i;3.) Pancreatic Hemorrhage and Acute Pancreatitis. (Surg. Gynec. & Obst., 1910, v. 10, p. 208. Also Ann. Surg., 1910, v. -M, p. 070-81.) Pancreatic Hemorrhage and Acute Pancreatitis, With a Report of Three Cases. (Tr. South. Surg. & Gynec. Ass., 1909; Phila., 1910. v. 22, p. 112-2.-).) Prognosis and Operative Treatment of Fracture of the Base of the Skull : Based on an Analysis of 190 Cases. (Ann. Surg., 1010, v. -M, p. 700-811. ALso Tr. Am. Surg. Ass., 1910, V, 28, p. 560-77.) 1911 (Ransohoff, J., and Ransohofif, J. L.) : Intrathoracic Surgery (Heart and Oesophagus Excluded). (Am. Pract. & Surg. (Bryant & Buck), 1911, ^.. 8, p. :l-.j8.) 1912 The Dissecting Room: Then and Now. (Lancet-Clinic. 1912, v. 107, p. 420.) Gastro-Enteroptosis ; When Is Surgery Indicated? (Surg. Gynec. & Obst., 1912, V. 15, p. 21-27.) Ice Tongs Extension for Simple Fracture of the Femur. (Tr. Am. Surg. .\ss., 1912, V. 30, p. 706-38. Also Lancet-Clinic, 1912, v. 108, p. 179-82.) Median Harelip. (Lancet-Clinic, 1912, v. 108, p. 48.5-87.) The Operative Treatment of (jastro-Enteroptosis. (Bost. M. & S. J., 1912, v. 107, p. 347-58.) Acute Unilateral Septic Infarct of the Kidney. (Lancet-Clinic, v. 1912, 107, p. 58:1.) Suture of Bullet Wound of the Lung with a New Method of Closing Pleural Defects. (Lancet-Clinic, 1912, v. lf>7, p. 517-19.) 1913 .\cute Perforating Sigmoiditis in Children. (.Ann. Surg. 1913, v. 58, p. 218-25. Also Tr. Am. Surg. Ass., 1913, v. 31. p. 422-:!(i.) Fat Hernia. (Lancet-Clinic, 191.3, v. 19, p. 6-10. Also Tr. South. Surg. & Gynec, 1912; Phila., 191:!, v. 25, p. 260-74.) Osteitis Deformans, Central Sarcoma, Streptococcus Infection. (Lancet-Clinic, 1913, V. 110, p. (i72-74.) What Can Surgery Do for Gastro-Enteroplosis? (Tr. South. Surg. & Gynec. Ass., 1912, V. 24, p. 5(i4-76 i Discussion |, p. 500-002.) 1914 Heredity in Bone Lesions, With the RepiTt of an Unusual Family History. ( Tr. South. Surg. & Gynec. Ass., 191:;; Atlanta. l!ill. v. 20, p. 10ii-7o.) (Ransohotf, J., and Kansohoff, ]. L.) : Radium Treatment of Cancer. (Lancet-Clinic. 1911, v. Ill, p. 6ill-7o.) 1915 Pancreatic Cyst as a Cause of Unilateral Hematuria With Report of a Case. (Tr. South. Surg. & Gynec. Ass., 1915, v. 28, p. lll)-2!l.) Status of Cerebral Surger>'. (Cin. Lancet-Clinic, 1915. v. 113, p. 537-41.) 1916 Addresses on Daniel Drake. (Lancet-Clinic, 1910. v. 115, p. 599-ti09.) Angina Ludovivi. (Lancet-Clinic, 191(), v. 115, p. 4:il-:!4.) RAXSOHOfF MEMORIAL VOLUME Dislocation of the Knee. (.Lancet-Clinic, liin;. v. llo, p. (i!l-7I. Also Tr. West. Surg. Ass., liU-J: Minneap., 191(i, p. Sl-90.) Pancreatic Cyst as a Cause of Unilateral Haematuria With Report of a Case. (Surg. Gynec. & Obst., 191(), v. -22, p. 21?,.} (RansohofT, J., and'Ransohoflf. J. L.^ : Radium Treatment of Uterine Cancers. (Ann. Surg., IHKi, v. W. p. •J!t,'<-:lii:!. .Mso Tr. Am. Surg. Ass., 191(i, v. :14, p. 202-12.) Radium Treatment of Uterine Fibroids. (Lancet-Clinic, lOlli, v. ll"i, p. llii-lS.) .•\ Simple Method of Draining Kmpycma. (J. .\m. M. Ass., IHH;. v. ilil, p. llDii.) 1917 Congenital Lipomata of the Cheek. (.\nn. Surg., 1917, v. fi."., p. 711-U. .Also Tr. South. Surg. .\ss., 191(1 ; Phila., 1917, v. 30, p. 65-69 [Discussion!, p. SH-S-V) Plastic- Surgery. (Ref. Handb. .\Ied. Soc, 1917, v. 7, p. 240-2.-)3.) Some Considerations in Brain Surgery. (Interstate Med. J., 1917, v. 24, p. .■i4:l-:>:!.) 1918 Hemorrhage from an .\neurism of the Internal Carotid -Artery, Following Septic Sore Throat. (Ann. of Surgery, UUS. v. liS, p. I'd-'i?,. .\lso Tr. .\m. Surg. .\ss., 1918, V. 3(i, p. 456-60.) On Injuries of the Cervical Spine. (Tr. South. Surg. .\ss., 191S, v. 21, p. 265-282. Also Surg. Gynec. & Obstet., 191S, v. 27, p. 241-47.) Teaching in the Hospital. ( Interstate M. J., nU.S v. 2--., p. 719-.V!.) 1919 Traumatic Facial Diplegia. (.\nn. of Surgery. 1!I19, v. 7ii, p. 1.VI-.56.) 1920 Empyema at Cincinnati General Hospital During Influenza Epidemic. (J. of Am. Med. Ass., 192n, v. 74, p. 2.38.) Hyperplastic Tuberculosis of Small Intestine. (.\nn. of .Sur^erv, 192", v. 72. p. 97-103.) John Hunter. (Cin. Journal of Med., 1920.) On the Borderland of Medicine and Surgery. ( Med. Bull. University of Cin., Nov., 1920.) EVA G. KYTE. AXXA J. DULING. MARGARET MURRAY. THE THERAPEUTIC POSSHULITIES OF llLO( )D TRANS- FUSION— Mr<:TH()DS. IXDICATIOXS AND R]<,SULTS* E. R. Arn, M. D., F. a. C. S. Junior Surgeon, Miami Valley Hospital. HISTORICAL CONSIDERATIOX, The operation of blood transfusion is an ancient one. Mention of it may be found in early medical writings. In early times it was attempted by using blood of lower animals. It was not until after the discovery of the circulation by Harvey, in IfiZS, that it was taken up with added interest, as well as along scientific and rational lines. Dr. J. B. Dennis, professor of physiology at the University of Paris, successfully performed the first trans- fusion of human blood to a jiaticnt in ir-67. This was done by means of a bone canula.' The Germans used defibrinated blood quite extensively in the early part of the nineteenth century. But because of the dangers of intravesical clot- ting, it was given up, and use of saline solution substituted. The modern practice of blood transfusion may be said to have had its origin in 1897, when Murphy reported his method of blood vessel suture in transfusion. In 1906, George W. Crile,- reported his special canula for transfusion. It was a marked advance in this work. The difficulties and objections to all of these methods were the, (a) wound on the donor; (b) obliteration of important blood vessels; (c) and difficulties encouiUered in technique. Further investigation developed the syringe method, Lindeman,^ the paraffined tubes of Kimpfon and Brown* ; the syringe method of Unger,^ and finally the anticoagulants of Lewishon.'"' The simplest as well as the most practicable of all of these is the anticoagulant or Citrate method, and is the method of choice in the majority of clinics today. TF.CHXIQUE OF CITRATE METHOD. The citrate method is the inethod in general use today. The apparatus necessary consists of the following: 1 Tourniquet. 4 Intravenous needles (Kaliski type). 4 Pieces of rubber tubing, 12 inches long. 18 Grains of sodium citrate. 1 30 cc. Graduate. 1 500 cc. Graduate. 1 Glass stirring rod. 1 Glass cylinder with 3 feet of rubl)cr tubing. 2 or more camliric needles. •Read t.rf,.. ll„ Si,,ti,,il S. >!> n „f tl,e Oliui .Slali- Mi-us anaemia and leukaemia, may be a life-saving measure in prolongation of the life of the individual. /;; pernieioiis anaemia, transfusion yields results superior to any other mode of thera/^y. Prcquently it acts as a life-saving measure by initiat- ing the onset of a remission. There is no evidence that the disease may be cured by this method. Repeated transfusions may be necessary, but the lives of many of these individuals can be made useful for years. They should all be grouped, and have at their command suitable donors. Small doses of blood seem to bring about a remission as quickly as large doses. Some donors seem to accentual c a remission sooner than others. In these cases the same donor should be UM'd for sulisci|uenl transfusions, as the dose of blood need not be large. RAXSOHOff MEMORIAL VOLUME A small percentage of eases of pernicious anaeina do not respond to transfusions, tlicy being of the so-called acute -i'ariety. Case illustrating tlie so-called chronic \ariety is as follows: Case No. . IMr. W., aged 52. Diagnosis, pernicious anaemia. Hcinoglobin 28 per cent, Sahli. Group II. 1, 950,000 R. B. C. Many normoblasts marked poikilocy- tosis, dyspnoea and palpatation on least exertion. Began to feel weak 18 months ago. and had to quit his occupation one year aao. TIail licen in bed most of the time for past two months. Was given 300 cc. ni I.Imi.iI at intervals of one week Group IV. donor, for three doses. Marked impmv i nu iit after lirst transfusion as evidence by Hb. 40 per cent Sahh., increasing appctitr, il\>iiiic'ca and palpatation less marked. Hb. 55 per cent after second transfusion, and was able to walk three squares to barber shop. Returned to his home in northern part of state after third transfusion. In acute lymphatic leukaemia, only a temporarily favorable effect can be secured by transfusion, even though we w^ithdraw a large amount of blood by phlebotomy and make use of a massive transfusion obtained from two donors, or employ repeated transfusions, or carry out transfusions very early in the disease. TR.WSFUSIOX IX IXFECTIOXS. Our greatest possibilities for research lie in Class \'., or the sub-acute and chronic infections. It has been fully demonstrated by clinical evidence that transfusions in localized pyogenic infections will increase the patient's vitality and aid in overcoming the infections. In bacteraemia, when the source of the organisms can be found and elim- I'nated, the results are excellent, as in cases of sinus thrombosis following mastoiditis, in which the jugular has been ligated. Many of oiu- long, drawn out cases of appendiceal abscess ami empyeniia would be materially shortened Ijy small therapeutic doses of new blood. Examples of this class are the following : Case Xo. . IMr. D. Diagnosis, secondary anaemia; Hb. ,^5 per cent, R. B. C. 2,500,000. Operated three months previous, at which time a left nephrectomy was done for pyonephrosis, secondary to renal calculus. Patient has made a very slow and discouraging recovery. Has been unable to work, and was confined to his home. Was given 350 cc. of blood, and ten days later 300 cc. more. .After second transfusion, patient was able to be up and care for himself. Returned to his home feeling stronger, and with a Hb. index of 65 per cent. Case Xo. . Miss A. Diagnosis, chronic empyeniia. Cavity of eighteen months duration, holding about 40O cc. Operated second time; Modified Shede operation, patient weak, pulse 116 to 120, and wound discharging large amount of pus. Was .given a therapeutic dose of 300 cc. of blood, .\fler two days, patient said she felt much stronger, wound began to sliow healthy granulation, discharge liecame less in amount, and pulse rate fell to ^8. Other examples abound, but these are sufficient to indicate the necessity of an awakening on the part of surgeons to certain definite deficiencies in their handling of anaemic, debilitated states secondary to chronic infections. If a person suffers a sudden loss of a great volume of blood, we make up the deficiency by adding fresh blood. Why, then, do we not likewise in the many secondary anaemias, that also suffer blood los.ses, but in smaller amounts and over longer periods? I have transfused a few of these chronics, and the new blood has done more to restore hope and sleep and appetite than Page IS E. R.ARN weeks of rest and barrels of iron and arsenic. I do not decry these neces- sary adjuvants in the least ; on the contrary, I advise their constant use, and have seen splendid results obtained. I merely deprecate and condemn their promiscuous employment in conditions beyond their therapeutic reach. They can do a certain amount of good, but in many cases they are absolutely worthless, and in many of these, one or more blood transfusions will almost produce a miracle, after which the drug and rest-therapy may be judiciously resumed. This has been proved, but has not been recognized. TR.VNSFUSION FOR POISOXING. Transfusions in this class are still in the experimental and research slage, except for poisoning from illuminating gas. This was one of the early fields for blood transfu.sii.ins, and consists of blood letting and blood giving. These cases are usually bled 700 to 1000 cc. and then transfused a similar amount.'" Cases in Class \l\.. are really a repetition of conditions described earlier in this paper. Kerley, in a recent article, has advised small transfusions in certain non-specific types of Marasmus. He usually gives several doses (jf not over 30 to 50 cc. at intervals of five to seven days. D.^XGERS OF BLOOD TRANSFUSION'. The dangers from blood transfusions can be easily avoided, and the operation made perfectly safe by avoiding the following: (a) Use of incompatible blood. (b) Excessively large transfusions. (c) Emboli of air or blood clot. Incoiiipatibilitv of Donor's Blood: Moss" has shown the presence in human blood of iso-agglulins and iso-hemolysins. These substances will cause agglutination and hemolysis of the red cells when incompatible bloods are mixed. Moss found that agglutination frequently occurs without hemo- lysis, but that hemolysis is always associated with agglutination. Human beings can be divided into four grou]is, depending upon agglutins present in serum, and the capacity of cells to agglutinate. Ha transfusion is to be safe, both the donor and the recipient should belong to the same group, or cells of the donor should not be agglutinated by serum of the recipient. These groups are permanent in their characteristics, and depend upon the Mendelion laws of inheritance. The following are the four groups with the percentage of indixiduals in each group : Group I., 10 per cent, of all individuals contain no agglutins. Group H., 43 per cent, of all individuals contain agglutin .\. Group HI., 7 i^er cent, of all individuals contain agglutin 1!. Group I\'., 40 per cent, of all individuals contain agglutin .\ and B. KJXSOHOFF MEMORIAL J-QLUME RELATIONS OF THE FOUR BLOOD GROUPS. Serum. Group : L n. IIL TV. ,.1 L X X X I. •S! n. o o X X TL s , in. o X X in. &i IV. o o IV. ^1 I. IL in. IV. It may be seen that no serum agglutinates the red cells belonging to its own group, but will agglutinate and may hemolyse corpuscles of other groups, except Group I\'. By having on hand serum of Group II. and III., the agglutinating and classifying tests are easily made, not reijuiring over fifteen minutes. We have made it a practice of having at our command suitable profes- sional donors, properly classified through physical examinations, and with negative Wassermanns. They can all be readied by telephone, and are paid a fee for their blood. By having this grouj) of ])rofessional donors, ihe time of making the tests is greatly lessened, and only need of classifying recipient or patient. In emergency, a Group lY. donor can be used to transfuse any other class. (No Asjsilutinins) (1. .\gylutinin "B.") I III 10% of all persons. 77c of all persons. (1. Agglutinin "A.") ( Both .Agglutinins ".\xB.") 40% of all persons. 43% of all persons. II IV MOSS AGGLUTINATION GROUPS. Essential for safety; serum of recipient should not agglutinate corptis- cles of donor. If you do not have professional donors suitably classified, it is always best to use the nearest blood relative. 'i'he second danger lies in transfusing an excessive amount of blood. This may lead to embarrassment of circulation, dilatation of the heart and and pulmonary oedema. The question of dosage is an important one and de- pends upon several factors: age of individual, condition tor which trans- fusion is indicated, and conditions of the circulatory apparatus, especially the inyocardium. /;; any form of inyociirdial dcraiujciiicnt, if transfusiofi ix indicated, small amounts should be given, and repeated at definite inter- I'als, to avoid invocardial embarrassment. E. R. ARM Generally speaking. 500 to 1000 cc. is the usual amount transfused, except in the blood diseases, in which 250 to 350 cc. seems to suffice to stim- ulate the blood-forming organs. Infants under six months of age receive 60 to 90 cc, given into the longi- tudinal sinus or jugular vein. Danger from emboli can be avoided by proper technique. In using citrate blood, we pass the blood through several layers (if gauze. RE.^CTIONS. The Mayo clinic reports 20 per cent, of transfused patients to have some degree of reaction. The Crile clinic does not report any reactions, believing them to be due to improper grouping. Our reactions have only licen two in our series, and both were due to faulty grouping. The case and siinplieity of the citrate method of trausfitsioii i^'ill siiij- ijest an increasing number of indications for its use. JVlio knuzcs. hat 7<'hat some of the acute infections may be treated l>y transfusions of small thera- peutic (liises of blood front donors immunized b\' the disease, or b\ raceina- tion/ The future ;il(>ne will solve these Cjuestions. As stated by one of the investigators, ihe subject of blood transfusions has thrilled the ini.-iginatiou of man, ever since the discovery of the circulation of the blood. In the last quarter of a century some of these dreams have been realized. The difficulties of technique of the old methods ; the uncertainty of success ; the pain, infection and life-long scars to patient and donors ; the imi^ericisms of its therapeutics relegated its use to the court of last resort. The newer method of blood transfusion makes possible new applica- tions. They open up a new field of therapeutics, a field that will possibly solve some of the jircscnt insoluble enigmas in the treatment of diseases, and in the conservation of human life. These matters are not caiialile of animal experimentation, and I cannot do more than suggest these possibilities to the medical men to develop them. The time has arrived when we should seriously begin to study blood dos;ige and therapy. CONCLUSION. 1. Salt .solution will never raise a blood pressure the second time. Transfusion of blood alone will save the patient. 2. The Citrate Method is the method of choice, because of the ease of application and preservation of important blood vessels for future trans- fusions, or other intravenous therapy, should occasion require. 3. Transfusion is a specific for haemorrhage of the new-born. In haemorrhagic diseases it will replace blood loss, stop the haemorrhage, but not cure the condition. 4. Transfusion saves delay and decreases morlalitv in cases with sec- ondary anaemia requiring operation, as fibroid tumors and jaundice. Paye HI RAXSOHOFF MEMORIAL VOLUME 5. Transfusion of blood opens a new field of therapy in the treatment of chronic infections. 6. IVIost reactions can be averted by making correct group tests, and transfusing from the same group, except in extreme emergencies, when Group I\'. may be used without grouping. In a series of one hundred cases, our reactions have been 6 per cent., and 4 per cent, due to mistakes in grouping. DISCUSSIOX. Dr. LiTEiER p. HoWKLL. Columbus : I wish to mention the facihty with which transfusion can be done in infants before closure of the anterior fontanelle. As you recall the superior longitudinal sinus anteriorly is located directly in the median line although at the posterior fontanelle it lies to the right. If the needle be introduced just anterior to the posterior angle of the anterior fontanelle and directed backward at an angle of 45 degrees with the interparietal suture to a depth of about one-sixteenth of an inch, the point of the needle will not impinge upon or injure the walls of the sinus, as it lies near the center of the lumen. The precaution must be made to keep the hand supporting the needle tightly steadied against the head and to inject the blood relatively slowly. Furthermore, in haemorrhage disease of the new4iorn it is necessary to type the blood, if that of the father be given and the use of onlv a small amount is necessary. Dennis. T. P..: Pliilos. Transact.. June 2S. lf.t.7. Crile. G. W.: Proc. Soc. E-Ni.er. Bi„l. an.i .\led.. \ol IV.. p. 0-8 Haemo rrhagt C. Y.. 1909. Lindman, E. : Amer. .Tour. Dis. Child, 1913, \o\ VI., p. 2 !8-32. Kimpton. .\. R.. and Brown. T. H.: Jour. .\. M. A.. 1913. Vol. IX I. p. 117. Un«r. L.: Journal A. M. .\.. 1915. Vol. IXIV.. p. 582. Lewishon, R.: Medical Record, Jan. 23. 1915. Blood Transfusion. Haemorrhage and the .\nemia s: Bernh ei,n. J. P., I. ippinc Lindeman. E. : Journal -A. M. -A.. 1919. Ungcr, L.: Journal A. M. .\., .August, 1919. I,andois, I.: Die Transfusion des Blutes, Berlin. 1911. Moss, W. L.: Johns Hopkins Hosp. Bull., 1910, Vol. X.\I. , p. 1.3/0. Pemberton, J. D., Mayo Clinic, \ol., 1918. OBSERVATIONS UPON SCARLET FEVER. DIPHTHERIA. AND MEASLES AT THE CINCINNATI CONTAGIOUS HOSPITAL.* By Ar.EivRT J. V,p.u., A. P., M. D., Visiting Staff, Contagious Group, Cincinnati Hospital. Although there are number.s of good men who, patiently and persever- ingly, are working in their laboratorie,s and wards upon the problems which our contagious diseases present, and the results of their efforts a]>pear at intervals, one is impressed with the comparatively little written upon the subject. I refer in this paper only to scarlet fever, diphtheria, and measles. This may be due to a placid conclusion on the part of many that our text- books have settled the clinical signs and symptoms and that repeated failures along etiological and bacteriological lines yield little of promise for the future. This I think is incorrect and someone's persistent eiYorts will event- ually be crowned with success. Scarlet fever appears variously disguised, probably more so than any other contagious disease, and if we can find out practically for ourselves that we have in the past laid too much stress upon certain so-called classical signs and not enough upon others and that a rearrangement of some of our ideas seems advisable, we may be helped to an earlier recognition and, there- fore, a luore prompt isolation and treatment of this atifection. During the last year in the contagious hospital we have had an excellent opportunity for studying this disease especially, and it is my desire to furnish statistics as we found them in this and the other diseases, with certain observations which were made concerning clinical manifestations, laboratory findings, and treat- ment. Observations were made upon over 300 cases of scarlet fe\cr. The following summary indicates in percentage form our findings in the so- called classical symptoms and diagnostic signs : Scarlet fever, 315 cases. Onset with vomiting, 50 per cent.; onset with headache, 4 per cent. ; onset with sore throat, 65 per cent. ; eruption, whole body, 46 per cent. ; eruption, partial, 35 per cent. ; mouth pallor, 57 per cent. ; rash on soft palate, 38.6 per cent. ; membrane on tonsils, 29 per cent. ; papill?e enlarged, 56 per cent.; glazed tongue, 17.7 per cent.; anterior cer- vical glands enlarged, 95 per cent.; submaxillary glands enlarged, 72 per cent. ; eruption gone from body, five and one-half days; desquamation began in six and three-quarter days; blood count, leukocytes average, 17,000; poly- morphonuclears, average, 78 per cent. ; large lymphocytes, average, 6.3 per cent.: small lymphocytes, average, 10.1 per cent.; eosinophiles, average, 2 per cent.; albumin, 11 per cent.; granular casts, 4 per cent.; hyaline casts, 2.5 per cent.; blood cells, 4 per cent.; myocarditis, 6 per cent.; irregular heart, 3 per cent.; murmurs, 8 per cent.; mastoiditis (no facial palsy in this series), 1 per cent.; arthralgia (all cases had immunizing doses of diph- 'From tl.e American Jmnnal of llie Medical Sciences, Novcnilier, 1912. Page SS RAXSOHOfF MEMORIAL VOLUME theria antitoxin), 6 per cent.; acetone, 49.5 per cent.; diacetic acid, 22.6 per cent. ; indican, 73 per cent. ; temperature gone in five and two-third days; nephritis, 2 per cent. The average white count of cases which died was 17,262. Preponderance of the staphylococcus may have influenced all leukocyte counts. Concerning the ahove summary a few comments seem pertinent : ( )nset with vomiting occurred in only 50 j.er cent, of our cases, which is rather disappointing, as so much stress has always been laid upon this sign. McCullom' says tliat it occurred in 80 per cent, of his cases, but Welsh and Schamberg give their figures also as 50 per cent., and add that they con- sider this rather lower than usual. I think that this is a just criticism and that in most epidemics the figures would be considerably higher. \Ve observed mouth jiallor in 57 per cent., which is also lower than we would expect. No statistics were olilainable from other sources in regard to this, McCullom merely s,iy> lli.it it docurs constantly in moderately severe cases. It has been our e.xiJcricnce that the rash occurs on the face in only a small number of the cases, but when this is present or if there is only a febrile blush upon the cheeks, the skin around the mouth and nose remains exempt. When this is seen I believe it to be quite characteristic. Thirty-eight and six-tenths per cent, had rashes upon the .soft palate and fauces and where this is present, namely, a generalized blush, punctate in character. I believe it to be our most important diagnostic sign. The papilke appeared enlarged in 56 per cent, of our cases. Concerning this McCullom says that the condition is constant, but may be missed at times, and Welch and Schamberg say that it may or may not be present in mild cases. When present, even with the glazed tongue (17.7 per cent.), it is not absolutely pathognomonic, as it may occur in certain forms of gastro- intestinal disturbance in which there is not the slightest suspicion of scarlet fever. The strawberry tongue, however, taken together with a. generalized blush, punctate in character, upon the soft palate and fauces, need leave very little doubt as to the character of the disease. I think these two symptoms arc \ery nuicli more significant than an apparently characteristic rash upon the body. We have tried to emphasize the importance of laying more stress upon the mouth .symptoms and not depending upon the body rash. However, the whole jjicture should be con- sidered Our average white count was 17,000. The maxinunn was viS.OOO. The text-books lead us to expect a uniformly higher count than this. We felt that a satisfactory one was between 20,000 and 35,000. Kotschetkofif and Bowi's" figures are between 10,000 and 40,000, Reider's 40,000, Felsenthal between 18,000 and 30,000, and Tileston between 18.000 and 40,000. The average polymorphonuclear count was 78 per cent. Kotschetkofif gives between 85 and 98 per cent. 1. Osier's Motlcrn Mcdirine. 2. Qnolcrt liy Welch and .Scli.im1)C.g. ALBERT J. BELL The low percentage of eosinophiles, 2 per cent., was probabl_v due to the fact that the blood counts were made early in the disease. McCulIom observed albumin in 72 per cent, of his cases at the South {department, while Roger reports 38 per cent. Our cases showed the pres- ence of albumin in only 11 per cent. I believe that a practical reason for this may be found in our routine treatment. All cases were confined to bed for at least three weeks and kept upon a strictly milk diet until their tem- ]ieratures were normal for seven days. Eggs and broths were withheld until the fifth week and red meats until the latter part of the sixth. Of equal importance with this is the systematic giving of large quantities of water from the time of their admission to the hospital. At first potassium citrate was ordered, more or less as a placebo, to be given hourly or two hourly in water, with the idea that the patients would get the fluid more religiously if medicine were ordered with it. How much restraining influence the alka- linizing power of this drug exerted upon the i)resence or absence of albumin in the urine we will consider later. In our estimate of nephritis we included all cases showing the presence of albumin, casts, and red blood cells, and this we found to be only 2 per cent. Welch and Schamberg'' quote Vogl as reporting 34 per cent, of nephritis in his cases; Cadet de (lassicourt, 30 ])er cent.; Ilaginsky, 9.57 jier cent.; Caiger, 3.32 per cent., and Holt gix'es as his figures between G and 10 per cent. Let me call attention to the fact that about 50 per cent, showed the pres- ence of acetone in the urine; less than half that number showed diacetic acid. and almost 75 per cent, reacted for indican. Practically all the cases desquamated, although some very slightly. None of our scarlet fever cases contracted diphtheria in the house, although two or three showed the presence of the Klebs-Loefiler bacillus upon admission. The most susceptible period for this disease is the third, fourth and fifth week. Variat and Deve report 30 cases positive for the Klebs-Loeiifler bacillus in 525 scarlet fever ]iatients ; Garret and Washburn.^ London Fever Hospital, report 1 per cent. ; \\'elsh and Schamberg,- Munic- ipal Hospital in Philadelphia found between 19 and 32 per cent, positive. Some allowance should be made for the method employed in reporting the presence or absence of the Klebs-Loeffler. We used the Westbrook classifi- cation entirely, which is liberal and will be referred to under diphtheria. At least four cultures were taken from the noses and throats of all scarlet fever patients. The so-called Pastias sign in this disease, namelv, the accentuation of the rash in the normal folds, especialh- on the anterior surface of the elbow. has not been noticed except in a few instances, so that no significance has been attached to it. RANSOHOFF MFMORIAL VOLUME Of like importance is the Rumpel-Leeds phenomenon or the hemorrhages at the elhow from compression of the upper arm by means of a bandage. Observations made by others have shown it to occur with equal frequency in measles and in normal children. In taking up the treatment of special conditions we may first refer briefly to the subject of immunization against scarlet fever. We have had practically no personal experience with this line of work, except to give one light case which was exposed to the most virulent form of the disease one million killed streptococci taken from scarlet fever patients (a vaccine which was on the market) and which case continued to ha\e a mild attack, and another, a very malignant case, five daily doses from 500.000 to 4,000,000 of the same scarlet fever vaccine. This patient's condition was uninflu- enced by the treatment and the patient died in a few days. The above should come under the heading of treatment of the disease rather than immunization. If there is any close connection between the streptococcus and the virus of scarlet fever we would look for our best results from an antistreptococcus serum, made from scarlet fever patients rather than a vaccine, as the former (the serum) already contains the antibodies and should act more promptly, while tlie latter (the vaccine) simply helps the patients to form his own. The field for the vaccine is in immunization. With the use of the ordinary antistreptococcic serum made up of streptococci not from scarlet fever patients we have noticed little benefit even in doses of 80 or 90 cc. in twenty-four or thirty-six hours. If it is used at all it should be made from the streptococci from blood, throat, or glands of scarlet fever cases. Such a serum has been hard for us to obtain from any source, because of tlie difticulty we have experienced in isolating streptococci from our cases. Federinski in ]VIoscow (1910). in an analysis of 317 cases which received the antistreptococcic serum (made from scarlet fever streptococci), says that it helps chances of recovery if given before the fifth day. His dosage was 200 cc. to adults and 100 to 150 cc. to children, repeated in twenty-four or forty-eight hours if necessary. Mathias Nicoll, New ^'ork (1910), re- ports only fair results. If obtainable, it should be used in some cases, in enormous doses always, for lack of something better, either subcutaneously or intravenously, according to immediate needs. It might help minimize the complications Professor Schwenkenbecker, director of the Frankfurt Hospital Medical Clinic, recommends the injection intravenously, not later than the fourth day, of serum (healthy as to syphilis or tuberculosis and culturally sterile), taken from at least three (namely, a polyvalent serum) scarlet fever cases suffering from a severe but uncomplicated type of the disease in late conval- escense. Treatment with this sera should cease not later than the eighteenth to the twenty-fourth day from the onset. The dose should be 40 cc. for children and 100 cc. for adults, and doses may be given at intervals of from ALBERT J. BELL one to seven days according to the severity of the case. He suggests that only the severe and unquestioned cases of scarlet fever be injected. Karl K. Koessler and Jessie M. Koessler.'"' in experiments concerning specific antibodies in scarlet fever, concluded that "the serum of scarlet fever patients contains specific antibodies for an unknown virus which seems to be present especially in the cervical lymph glands." Personallv, I think that we should direct out eflforts toward discovering a specific serum for the treatment of this disease to the preparation of sera derived from the blood stream or, more probably, from (lie cervical lymph glands of scarlet fever patients, rather than to vaccines or serums containing the streptococcus or its antibodies. Out of 50 or more nurses who have been on duty in the wards, three (about 6 per cent.) contracled the disease in the house, while none of the internes did. W. H. Waters, of Boston, reports results in immunization against scarlet fever, of nurses on contagious duty. He used diiiferent strains of strepto- cocci, killed and standardized in usual way, taken from throats of scarlet fever patients. For two or three weeks before going on duty the nurses received three immunizing doses, of 50,000,000, 100,000,000 and 200,000,000 organisms of a polyvalent vaccine. Of those receiving the vaccine 2.7 per cent, contracted the disease and of those not receiving it 35.7 per cent, con- Iracted it. These figures are rather amazing as his nurses must have been unusually susceptible. Kolmer of Philadelphia, in trying to raise the streptococco-opsonic index, found experimentally that he was able to do so slightly, but concluded that it was so slight as to make the likelihood of establishing an immunity against streptococcic infection very dubious. Again, in experimental studies on streptococcus antibodies with special reference to complement fixation reac- tions, he concludes that a streptococcus produces a specific antibody up to a certain limit, but "finding but 11.2 per cent, of positive reactions in scarlet fever tends to show that streptococcus infection in scarlet fever severe enough to produce immune bodies is not so common as is generally believed," Nasal and ear discharges were reported promptly and a number of auto- genous and stock vaccines (in all ten, an inconclusive number it is true~) were prepared. It is the opinion of most workers that stock vaccines gi\e equally as good, if not better results than the autogenous, because the former can be administered much more promptly and several days are gained for the patient, a very important consideration. Our results with these vaccines were not brilliant. Cases using vaccines had no local treatment. Irrigations were employed for the others. Except in one or two instances we could not see that the discharge was in any way modified by the vaccine and on the whole, those having local treatments ran a shorter course. The dosage in 6. Jour. Infect. Dis., Novcniliev, 1911, v,.l. i.x. No. 3, Page 27 RAXSOHOFF MFMORIAL VOLUME each case was started with ahout 200.000 and each succeeding dose was doubled at intervals of from two to ten days, according to indications. This was carried up to 128.000,000 in some cases. Tliis method has so far been disappointing, but in the hands of Kolmer. of Philadeljihia, good results have been reported. It is possible that in some instances our intervals of administration and dosage were faulty, yet the method is certainly in line with modern vacine therapy in other directions. Many cases, however, hav- ing local treatments, where intelligently applied, yield results, which, if vaccines were being used, would be considered brilliant. We have taken the opportunity in our wards of applying where\er feas- ible, the treatment for nephritis as suggested by Dr. Martin Henry Fischer.' This therap\ is based upon certain theories, or more correctly, facts, since they have been confirmed by laboratory experiments and as they are a departure from our formerly accepted views on nephritis, it may be well to briefly summarize a few details of his work and conclusions for the benefit of those who are not familiar with them. They are as follows : It is assumed that nephritis is due to an acidosis in the kidney. Empha- sis is laid upon the colloidal structure of the blood, both red and white cor- puscles and the lic|uid ]X)rtion, also that the urinary membrane, namely, everything between the urine and the blood, consists of various emulsion colloids in the solid state. Colloid material is also present in the urine nor- mally, but is not visible as albumin to our ordinary tests. The fluids and tissues of the body (except the gastric juice, urine, sweat, vaginal secretion, and alimentary contents, when fat is fed) are practically neutral in reaction. Normal blood is neutral in reaction, but contains both alkalies and acids. An abnormal production or accumulation of acid in the kidney renders the colloidal urinary memliranc solul)le and permits a part of it to ]iass into the urine as albumin. This has been demonstrated bv ex])erimcnts. Fibrin, an albuminous structure, when mixed and shaken with plain water (of neutral reaction) swells only slightly and the water shows no reaction for albumin. If h)dro- chloric acid is added there is greater swelling of the fibrin and albumin is present (by the precipitation of the fibrin) in the water in accordance with the amount of swelling. If sodium chloride or any other salt is mixed with the hydrochloric acid, less albumin goes into solution, the higher the con- centration of the salt. Geletin (anotlier colloid) acts practically the same way as fibrin. A high alkali content can as readily put the colloids, fibrin, and gelatin into solution (namely, dissolve the albumin) as can an acid. This is jn-ob- ably no factor in the production of a nephritis as the normal (!^J. ijroduction in the living cells tends c|uickly to neutralize it. Fischer found that liy injecting acid into the ear of a ralibit, its nor- 7. Nephritis. Page 2S ALBERT J. BELL mally alkalin urine became acid. Albumin, casts, epithelial cells, blood cor- puscles, and hemoglobin appeared promptly in the urine which was also diminishefl in cpiantity. Edema of the tissues was noticed as well. An over snppl}' of acid in the tissues in extreme muscular exertion anrl the se\rrc ;ineniias, without adequate oxicl.-ilinn. shnws alhuniin in the in'ine. Contrary to the views of many, he holds that albuminuria is the constant accompaniment of salt star\ation. Actual experiments on the kidney by Fischer are in line \\ilh the pre- ceding observations. He found that the structures of the kidne_\- in the pres- ence of an acid swell, take in water, and part of the colloid material is dis- solved as albumin and precipitated as granules. This brief summary suggests the "Fischer" treatment for nephritis, namely, an alkali, salt, and plenty of water. It occurred to us that as the contagious diseases are frequently accom- panied by an acidosis, as exemplified by the presence of acetone in about 50 per cent, of our cases and diacetic acid in 22.6 per cent., that the alkaline treatment might help to control the progress in the severe septic types of the disease. Apparently it exerted little or no influence in staying the coiu'se of the purely septic types which were unaccompanied by any special ni'phri- tis. Fischer says that he would not exjiect it to have any material influence upon that type of case. Sodium carbonate given by the mouth was not well tolerated as a rule, and seemed to be somewhat more irritating to the rectum than a normal salt solution. However, a large majority of the cases retained a sufficient amount in that way. Potassium citrate was substituted when giving an alkali by mouth and has been given to all my cases hourly or two hourly, whether or not they had evidences of albumin or nephritis. Prob- ably the low percentage of albuminurias (11 per cent.) and that of nephritis (2 per cent, in 388 cases of scarlet fever) observed in our wards is due to the routine alkaline "plenty of water" treatment, which all the cases have had. Their urine part of the time was alkaline and never highly acid. Two cases present interesting features : Case I. — M. D., male, aged three years. vSevere se])tic type with liotli ears discharging, profuse nasal discharge, enlarged glands, weak, irregular heart with bruit at apex, eyelids, and feet edematous. Urinalysis, albumin negative. Amount of urine \ery scanty, blood cells and hyaline casts. Started alkaline-salt solution per rectum. The solution contained sodium carbonate (crystals) 10, sodium chloride 10, in 1000 cc. of water. A half strength dilution of the above was used. Four ounces were given per rectum every three hours and were expelled occasionally. Potassium citrate, grains live in water, was given by mouth every one to three hours. On the ninth day of the illness Fischer's solution was gi\en intraven- ously. Same formula as above was used except that sodium cbhn-ide \\,-is increased to 14 in the 1000 cc. of water and a half dilution given. ( )nl\ 10 ounces were used as the patient showed signs of collapse. At least a pint Fagc S'J RAXSOHOFF MEMORIAL VOLUME and a half should have been gi\en very slowly had we been able to do so. Next day one pint was given again intravenously. The amount of urine passed increased promptly, and the edema disappeared. Gradual improve- ment of general symptoms with complete recovery resulted. Case II. — J. D.. male, aged four years. Light case of scarlet fever with temperature reaching normal on the fifth day. He passed from 8 to 33 ounces of urine daily up to the thirty-first day of the illness. On the twenty- seventh day (end of fourth week) the urinalysis showed: Specific gravity, 1010; albumin, a heavy trace; few coarse granular casts; red and white blood cells. The child was somnolent and was aroused with dilticulty. \'omited sev- eral times. Pulse varied between 90 and 122. with blood pressure high (systolic pressure sometimes reaching 144). The child seemed on the verge of uremic convulsions. There was pufliness of the face and eyelids and slight edema of the feet. There was no fluid in the serous cavities at any stage. For thirteen days after the nephritis commenced, except once, albumin from a slight to a heavy trace was reported daily in twenty-four hour speci- mens. It then disappeared not to return again. During the presence of albumin, red and white cells were found in abundance. Casts were rare. An occasional granular, and a few blood casts were reported once and part of one cast another time. There were no hyaline casts. After eight days the blood cells were few in number and gradually disappeared, to be entirely gone about the eighteenth day. The specific gravity varied between 1002 and 1028, usually between 1002 and 1010. The urine was reported as acid only twice after the fourth day. The amount of urine passed daily varied from 30 to 60 ounces. Treatment. The treatment was as follows : For ten da}s after albumin was discovered the patient had sodium chloride, grains five, and potassium citrate, grains eight, by mouth in as much water as he would take every hour, day and night. Fischer's solution, one-half dilution (of the sodium chloride 10, sodium carbonate, crystals 10. water 1000 cc. strength), ounces five, per rectum was given at two-hour intervals during the day and three- hour intervals during night, and was retained. After ten days the intervals of administration both by mouth and rectum were lengthened. During the period of high blood pressure, veratrum viridi. minims two. every three hours, was given during the day. Fischer's solution intraven- ously was not necessary. Blaud's pills were started during convalescence as a tonic. During the attack the child showed a mild grade of anemia. The red blood cells were 4,600,000. Recovery was complete. There were several interesting features about this ca>e. He started with what appeared to be a terrific case of nei)hritis with the urine absolutely loaded with red blood cells and a large amount of albumin. One striking Page 30 ALBERT J. BELL thing was the great scarcity of casts of all descriptions. How much this was influenced by keeping the urine absolutely alkaline, by the constant administration of salt, and the ingestion of large quantities of water, is an interesting question. With the starting of the treatment all symptoms improved and continued to do so consistently. We found that grains twelve to thirteen hourly of potassium citrate by mouth in the adult and grains five to seven in children, aged four to seven years, was sufficient to keep the urine alkaline. As I have said before, nephritis has been of rather rare occurrence in our wards, but whenever tried the alkaline salt treatment has given satisfac- tory results. True relapses or reinfections were not observed, but delayed rashes occurred in one or two instances. Eighteen blood cultures were made during the year from scarlet fever patients. Of these nine were negative. In the other nine cases the staphy- lococcus pyogenes aureus was recovered seven times and the albus twice. We were unable to recover the streptococcus from the blood. The throat and nose cultures almost uniformly showed the presence of staphylococci, occasionally mixed with a few streptococci. Atmospheric plate cultures (88 in number) in wards before fumigation showed the presence of the staphylococcus aureus and albus, the strepto- coccus pyogenes, but never the Klebs-Loefifler bacillus. After fumigation with formaldehyde, plate cultures were always negative. Twelve cervical glands of scarlet fever patients were aspirated with aseptic precautions in an effort to corroborate the claitns of X'ijsond made in the spring of 1911, that he had found the specific organism of scarlet fever in the glands of patients suffering from this disease. The cultures were sterile in nine cases ; the staphylococcus pyogenes aureus was isolated twice and the pyoscyaneus once. Our results did not verify his findings. This has also been the experience of others. Experiments by Dr. Nicoll .show that Mpond's bacillus was probably a contamination from the asbestos packing of his syringe. The following summary shows observations made u])on 76 cases of diphtheria : Onset with sore throat, 84 per cent.; onset with vomiting, ii per cent.; membrane on tonsils, 85 per cent. ; membrane on soft palate, 36 per cent. ; inflammatory swelling, 30 per cent. ; membrane gone on the average in two and seven-elevenths days ; temperature normal on the average in three and three-quarter days; erythema (not from serum), 5 per cent.; urticaria (not from serum) , 14 per cent. ; otitis, 5 per cent. ; albumin, 12 per cent. ; adenitis, 47 per cent. ; paralysis, soft palate, 5 per cent. ; paralysis of other muscles, 4 per cent. ; myocarditis, 16 per cent. ; endocarditis, 28 per cent. ; slow inilse, 4 per cent.; arthralgia, 2.6 per cent.; acetone, 28.5 per cent.; diacetic acid, 14 per cent.; indican, i2 per cent.; serum rashes, 16 per cent.; antitoxin, RANSOHOFF MFMORIAL VOLUME average dose. 4O,C0O units; highest dose, 355.000 units; l)l()od count: Leukocytes, average. 13,633. Types of Klebs-Loeffler bacilH found in Wesbrook ckissitication : C, 58 per cent. ; D. 39 per cent. ; A. 22 per cent. ; E, 8 per cent. ; E. and Fo, 5 per cent. ; B, D,. and F,, 3 per cent. Other solid forms occurred less frequently. Glancing at the table we see that vomiting occurred at the onset in only 18 ])er cent, of the cases, while in scarlet fever the percentage was 50. A striking feature about the table is that the average dose of antitoxin was 40,000 units. This is accounted for by the fact that a number of desperate cases, having been sick about a week before admission, required enormous doses which brought up the average considerably. Many re- quired only small doses. Our rule w^as to give from 2000 or 3000 to 12,000 units from two to three times in twenty-four hours, until signs of improve- ment were noticed. A husband and wife, sick one week before admission, came in completely overwhelmed by the disease. The former had the pharyngeal type, his pharynx being completely covered by a membrane about one-eighth of an inch thick. He had the record dose, 355,000 units. He developed some arrhythmia, but showed no serum rashes or arthralgia. He was in an advanced stage of tuberculosis before acquiring diphtheria and died from that disease later. His wife had a bad laryngeal type of diphtheria, with pronounced stenosis, loss of voice, and extreme prostration. She received 345,000 units and made a complete recovery, without serum rashes, arthral- gia, evidences of myocarditis, or any other complication. .Xdxanced laryn- geal cases received antitoxin unsparingly. Whether or not hospital cases receive more antitoxin than is absolutely necessary, they, at least, cannot be judged by the standard set in private practice where the cases receive treatment promptly. Our cases show some features which are worth mentioning. 'I'he average time for the disappearance of the membrane was two and two-third days and normal temperature averaged three and three-fourth days. Paralysis of the soft palate occurred in only 5 per cent. Other paralysis, 4 per cent. .Arthralgia was noticed in only 2.6 per cent, and serum rashes in 16 per cent. Concentrated serum was always used. No anaphylactic phenomena were observed in any of our cases. Our mortality for diphtheria as reported up to January 1, 1912. was 3j/i per cent., while for scarlet fever it was 6.5 per cent. This is at least an illustration of the principle that large doses of antitoxin need not be feared, and that it neutralizes all the toxin. The con- verse applies forcibly to insufficient dosage. Promptness in administration is an important guide to the size of the dose. The Wesbrook' classilication was used routinely in examinaticjns for the Klebs-Locffler bacillus. .A, C, and 1). the granular types, were regarded Public Hygiene. May, ALBERT J. BULL as positive and when found three successive negative cuhures were required before discharge. A,, A,„ B, Bo, C, C.. and E (the barred types except E), were called doubtful, and when found put the patient back for only one culture instead of three. The solid forms were regarded as negligible. This method is a liberal one. as it makes a distinction between the virulent and non-virulent types. Xo use was made of the Diazo reaction in di])luheria as a differential sign between a purely serum rash and true scarlet (.)r measles. It occurs in 17 per cent, of scarlet fe\er cases, 12 per cent, of diphtheria, and 75 per cent, of measle cases. In the latter it might be helpful. Little difficulty was experienced with the persistence of the Klebs-Loeffler bacillus in the throats of convalescing individuals. This happened only two or three times. The early negative findings were undoubtedly influenced by frequent throat irrigations and sometimes nasal, of normal salt solution or bichloride solution (1 to 12,000) or simple applicatons of the latter (1 to 4000). L. M. DeWitt and others recommend the application and sprays of fresh cultures in broth of the staphylococcus pyogenes aureus for persistent Klebs-Loeffler bacilli in the throat. This should not be done until convales- ence, when the mucous membrane presents a normal healed surface. There is no incompatibility between the Klebs-Loefffer and the staphylococcus, but the latter assists in reinforcing the normal throat flora. Max Crohn'' recommends small doses uf antitoxin (2000 units) subcu- taneously for post-diphtheritic paralysis and reports good results. We have not tried it, and should hesitate to do so except in very favorable cases for fear of serum sickness. BingeP" recommends intraspinal injections of diphtheria antitoxin for late cardiac failure after this disease. The condition is so grave that any- thing which gives even remote promise should be tried. Cumberlage, of England, recommended the use of antitoxin by the mouth. The initial dose was 4000 units, followed up if necessary by 2000 units more. He did not observe serum rashes or joint pains following the use of this method, and obtained result within a few hours after administration. W'e tried this with a few cases (five in number) and selected them with reference to mildness rather than severity of type. It was administered in milk and usually well borne. We used only small doses, but seeing very slow response gave more than he recommended. The average disappear- ance of nasal discharge was five and one-half days and of membrane on the tonsils seven and one-third days, as opposed to the subcutaneous method, which was two and two-third days. RAXSOHOFF MEMORIAL VOLUME \\'ith the injection of diphtheria antitoxin intravenously we have had no experience. E. Freedberger and S. Mita" claim from their experiments that larger doses may be borne and that there is less chance of an anaphylactic reaction when applied directly to the blood stream and so avoiding a reac- tion with the body tissues. In very desperate cases it might appeal to us as offering a better chance to more promptly neutralize the toxins. Acetone was found in our diphtheria patients in only 28.5 per cent., but only one examination was made for each of the cases. F. Reicher.'= of Hamburg, found it in 65 per cent, of his diphtheria patients during the febrile stage and in 40.2 per cent, of all other anginas and is. therefore, inclined to regard it as of diagnostic signiticance. I cannot see that it is needed especially as an aid. for either a laboratory or clinical case of diphtheria will have its apjiropriate treatment. Even in private practice one should not be satisfied with just one negative culture. Our routine method of staining for the Kelbs-Loeffier bacillus lias been done with the standard Loeffler's methylene blue. \'ery recently we have tried in conjunction with this a slain jiroposed by Dr. Marie Raskin'^ in a paper read before the Royal Clinical Institute, of St. Petersburg. The solu- tion is composed as follows: 5 cc. of glacial acetic acid. 95 cc. of distilled w-ater, 100 cc. of 95 per cent, alcohol, 4 cc. of an old and long-standing methylene blue solution, 4 cc. of Ziehl's carbol fuschin. The method is to drop the mixture on the prepared slide and then boil over a flame for eight to ten seconds. After five seconds tlie slide i> washed in water, dried, and examined. The polar bodies ajjpear as deep blue, while the rod is a bright red. Practically, our stains so far show the rods to be a pinkish color, while the granules stand out very well as dark bodies. ( )ther rods and cocci like- wise take the pink stain. From our limited experience in its use, it appears to be a good stain and I think that the polar bodies stand out more promi- nently than with the methylene blue method alone. Before closing let me mention a few observations concerning measles and rubella. Our average white count for all ages in both was between 7000 and 8000, somewhat higher than we would expect. All had an increased polymorphonuclear count. The cervical and submaxillary glands were enlarged in practically all of our rubella cases, but in none markedly so. The submetal gland was enlarged in a few cases (recent cases show their presence more often), the post-auricular were enlarged more frequently. In rubella the rash was of the macido-papular type in 81 i)er cent. : of tiie erythematous type in 19 per cent. In measles, acetone and diacetic acid (each) were present in 22 per cent which is, I believe, lower than usual. Indican occurred in 88 per cent. 11. ncutscli. med. Wocli., rel)iuaiy. 1912. 12. Miinch. med. Wocli., October, 1911. 13. Dentsch. med. Woch., December, 1911. ALBERT J. BELL In rubella both acetone and diacetic acid were negative in all cases, a fact which may be found to have some diagnostic significance ; indican was posi- tive in 50 per cent. In conclusion I wish to express my appreciation of the efficient work done in the laboratory by Dr. William H. Peters, the bacteriologist, and liy Mr. King and Mr. Bader, of the Ohio-Miami Medical School, whose results are incorporated in this article. To Dr. Samuel Zielonka I am indebted for several valuable translations. It would also be unfair to close without grate- ful recognition of the services of the internes and nurses who, from time to time, have been on duty at the hospital, for without their help this paper would have been impossible. REPORT OF XIXETEEN CASES OF HYPERFLASIA OF THE THYMUS i;LAND, TREATED BY THI-". X-RAYS.* By Jri.iEx E. ]]enjamin, M. D.. and Sidney Lange, M. D. Cincinnati. HISTORICAL. In 1855 Kajip called attention to in.stances of sudden death.s in child- hood following cyanosis and stridor, in which at autopsy nothing abnormal except an hjperplastic thymus could be found. Since that time clinicians have paid much attention to thymic hyperplasia and faulty involution thereof. The studies of .-\. Paltauf in 1889 established the frequent com- bination of hyperplasia of the thymus with status lymphaticus and aplasia of the cardio-vascular system. It was he who called attention to the neces- sity of considering causes other than mechanical in the sudden deaths among such ])atients. He spoke of a disturliance connected with a "lymphatico- chlorotic constitution." For a long time it was thought that an abnormally large thymus was always accompanied by a status lymphaticus. but it is now delniitely known lliat a status thymicus can occur independently of a status Ix-mpliaticus. This has been proven from both laboratory and clinical standpoints. For instance, W'eisel and Hedinger- have shown that hyperplasia of the chromaffin system and status lym]jhaticus go hand in hand, while in pure hypertro]ihy of the thymus this is not true. The cases which are recorded in this pajx-r rejirescnt a larger number of cases of true thymic hyperplasia than have heretofore l)ecn rc]3orted. In no case were there symptoms of status lymphaticus. Thymic hypertrophy thus became a distinct entity with as yet no cure. In 1896 Rehn reported 5 cases of thymectomy for the relief of tracheal obstruction. Shortly before this thymopexy was employed, but was ;i com- jiletc failure, excej)! for temporary relief of stenosis. Thymectomy was resorted to entirely in these cases until 1903, the mortality associated with this operation being about 11 per cent. In this year Heinicke" showed that X-rays have a profound influence on lymphoid tissue in the guinea pig, espe- cially on the thymus gland. With this discovery a very valuable chapter was added to medicine, for it was not long liefore it was shown that by the immediate and intensive application of X-rays, the most hopeless case could be saved ; also, that all the symptoms resulting from an enlarged thymus could be permanently cured by subsequent dosage. The first case thus treated was reported by Dr. .\lfred Friedlander.^ Led by the work of Heinecke, Dr. Friedlander and Dr. Sidney Lange first worked with guinea pigs, noting the efi:'ect of frequently repeated exposures on the lymphoid iLssues. Not long after this a case of acute tracheal stenosis on the basfs 'From A.chive.s of Pediatiics, I-cbni.iry, 1918. Rend befoi n.ili, Ohio, l-\bru:iry, 1917. JULIEN E. BENJAMIN AND SIDNEY LANGE of thymic hypertrophy was relieved and permanently cured by the applica- tion of the X-rays. At this early date one difficnlty existed. Radiography was far from its present stage of perfection and it was almost impossible to obtain clear pictures of the thymic region. Furthermore, there was no real accurate method of measuring dosage. It is because of the i>assing of these diflicullies that the present report and results are possible. I'his stud}' criniprises one year's observation on all kinds of cases coming under our su]ier\isi(in at the Children's Department of the University of Cincinnati ( Uhio-Miami Medical College) Clinic. A total of 225 cases were seen in that time, of which 19 showed undisputed evidence of enlarged thymus, or 8.47 per cent. The diagnosis of an enlarged thymus is usually simple. The chief com- l)laint is nearly always, coughs or attacks of choking which come and go. appearing frequently in paroxysms. One point of interest is the fact that the mothers usually explain that the child does not show the prodromal symptoms of a cold, but while apparently well, begins to cough during the night. This is repeated for several nights and then disappears, to return in a similar manner in a very .short while. Only on further cross examination is the information elicited that there is noted occasional cyanosis or tend- ency to choke or stridor. Most of the cases were very well developed and nourished. The lymphatic glands, other than the posterior cervical glands showed no hypertrophy as a rule. The spleen was found enlarged in only two cases. The lungs were, as a rule, peculiarly free of rales. In outlining the gland the following method, spoken of by Sylvester'' and others as "Threshold Method of Percussion" was always employed: The child is placed on the mother's lap on his back. Percussion is begun well out in the chest with such light strokes that when the ear is within a few inches of the area under percussion only faintest possible resonance is heard. When sound disappears, dullness begins. Some observers outline the borders of dullness by the tactile sense of resistance rather than soinid. 'IMie outer limits are determined much more easily than the lower boundary. The lower boundary, which may be oljtained by auscultatory percussion is relatively less important. The percussion outlines, determined in this way, correspond remarkably close to the roentgenograms. All cases showing enlarged thymus by physical examination or in which there were suggestive symptoms of this condition were submitted for X-ray examination. Treat- luents were only given to those showing positive X-ray findings. It is most interesting to note the rapid impro\-ement under roentgeno- therapy. Beginning with the first treatment marked [progress is usually noted. Shortly after the second treatment the cough has usually abated. With the improvement in symptoms goes a corresponding shrinkage in the size of the gland as shown by subsequent radiograms. The iiarents were always cautioned about relapses which occur in a cer- tain number of cases and directed to return for treatment regardless of Page 37 RAXSOHOPF MEMORIAL VOLUME appearance of symptoms within six weeks of the last treatment. Three treatments are the usual number given. In reviewing the clinical literature of the past five years one is struck by the small number of cases reported of this apparently common illness. Furthermore it will be noticed that most of the cases which do come into ])rint have been of the fulminating type. It is altogether likely that the cases coming under this series represent earlier stages of the more severe kinds. In other words, were they to have had intercurrent infections while in the stage of hyperthymetism more urgent symptoms might have been noted. It is probable that the condition was remedied before further symp- toms could develop. The condition is important enough to deserve more attention than has been given to it in the past. Early diagnosis and prompt therapy may be the means (jf eliminating most of the sudden deaths among infants and young children. Dr. Lange outlines his method of treatment as follows: All of the chil dren who were referred to the X-ray laboratory, were first radiogra])hed to Plate 1. r G of iidcturnal cmul .Vote lirnadetiMig it confirm, if possible, the clinical diagnosis. To obtain trustworthy X-ray plates of these cases certain details of techni(|ue must be ob.served. Un- doubtedly the difficulty experienced in some laboratories of establishing definite X-ray diagnoses of thymus enlargement has been due to a failure to observe these details of technique. Indeed, in many large clinics the great frequency of enlargement of the thymus glands in young children has been overlooked and in some instances even doubted. While a clinical diagnosis of thymic enlargement is not always difficult, yet it is never absolutely posi- tive without X-ray confirmation. This X-ray confirmation, taken in con- junction with the startling results of X-ray therapy, eniphasizes this condi- Pagc 3S JULIEN H. BENJAMIN AND SI DN EY LANGE tion as a distinct clinical entity and leads to the recognition of many cases which would be otherwise overlooked. The child to be radiographed must be placed flat upon the back. There must be no tilting to either side. If there is the slightest lateral tilting there is produced upon the X-ray plate an asymmetry of the two halves of the chest and a "flopping" or displacement of the mediastinal and heart shadows to one or the other sides. X-ray plates produced under such conditions are usually valueless, as they cannot be accurately interpreted. It is not always easy to place very young infants symmetrically upon their backs, but repeated trials must be made until a plate is produced which shows the chest areas, that is, the distances from the midline of the spine to axillary borders of the ribs, to be equal on the right and left sides. Under these conditions, enlarge- ments of the upper mediastinal shadow, whether to the right or to the left of the midline, can lie readily recognized. It is essential in the making of these radiographs of very young children that the exposures be almost instantaneous. The reasons are obvious. as Plate 1. November 7, 1916, after tlire relief of symptonr^. In the series here presented the time of ex])osure varied from one-sixtieth to one-thirtieth of a second. Even with such short exposures it is not always possible to secure absolutely sharp contours upon the plates. If the time exceeds one-thirtieth of a second there restilts an amount of blurring of the shadow contours which usually renders the interpretation inaccurate. A very soft X-ray tube should be used on this work, as the delicate thymus tissue will fail to cast a shadow upon the X-ray plate if the quality of the X-ray employed be too hard or penetrating. As previously stated, the X-ray diagnosis of thymic enlargement is based upon an enlargement (usually a lateral enlargement) of the thynuis shadow, which normally rests upon and is continuous with the heart shadow. RAXSOHOFf MEMORIAL VOLUME Since the breadth of the upjier mediastinal shadow \-aries normally with the age and general condition of the patient and since it may vary from time to time even in the same patient, the X-ray diagnosis is not always easy or free from error. In one case, not included in this series, an apparently normal thymus shadow was obtained when the child was quiet or sleeping, but during a restless crying spell the thymus shadow became greatly enlarged. The X-ray shadows of congenital heart enlargements are often confused with th}'mic enlargements. In all cases in wiiich the X-ray diagnosis seemed doubtful an X-ray exposure was given as a therapeutic test, and this test has proven very reliable. It must be conceded, in this connection, that many sym])tomless and apparently healthy children may show an appar- ently enlarged thymus upon the X-ray plate and this fact has been illogically cited as evidence against the accuracy of the X-ray diagnosis and the value of X-ray treatment of thymic enlargements. An enlarged thymus in an apparently healthy child may be abnormal although its ill effects may not be manifest until some added strain be ])u( u[)on the heart or respiratory organs or until the resisting powers of the child be called upon to overcome an acute infection. Post-morten evidence is not always conclusive in these cases as a thymus enlarged intra vitam may collapse after the circulation is abolished, although such post-mortem findings have been cited as indicat- ing inaccuracy in X-ray interpretation. The X-ray therapy was carried out in this series of cases as follows : A Coolidge tube backing up a 9^/2 -inch spark was employed. The rays were filtered through four millimeters of aluminum and a piece of thick leather. The target skin distance was approximately 9 inches. The routine exposure was 25 milliampereminutes. In mild cases a single dose given over the anterior surface of the chest proved sufiicient. In more urgent cases 50 milliampereminutes were administered at the first treatment. 25 anteriorly and 25 posteriorly. During the treatment the child was kept quiet by four sandbags, one placed across each arm and one across each leg. The interval between treatments was usually one week unless the urgency of the symp- toms suggested more frequent applications. The treatments have proxen entirely harmless to young children, and if the symptoms are very urgent a .second dose may be given within a day or two after the first. In order to get results it is essential that the treatments be comparatively heavy and that they be repeated at sufficiently short intervals. The failure to adminis- ter full doses and to repeat them promptly has in very urgent cases led to fatalities under X-ray treatment. Such a distressing occurrence is fortu- nately uncommon, but when it does happen it casts a doubt upon the diag- nosis or upon the efficiency of the X-ray therapy. To guard against sud- den deaths before the full destructive effect of the X-ray upon the thymus gland has been elicited, all cases with urgent symptoms should be kept under close observation and the X-ray treatments should be pushed boldly. Page Ifi J U LI EN E. BENJAMIN AND SIDNEY LANGE In the average case improvement of symptoms has been noted within 24 to 48 hours after the X-ray treatment. It is possible, however, as shown by animal experimentation, to elicit changes in the tliymus gland within eight hours after the X-ray exposure. Therefore the most urgent cases can be saved Ijy this treatment. COX'CLUSIOXS. 1. 8.4 per cent, of cases show enlarged thymus. 2. Physical examination. History of symptoms are suggestive of diag- nosis. X-ray examination is positive evidence. 3. X-ray treatment produces definite cures. HlBLlOr.R Paul au f. A. Wien Klin W ocli., 1889. > Hedi ngcr, E : Fran kfort Zei 5icli, Path., \ Miin ell. Med Wocli. 1903 p. 2,090; 1904, Arch ve s of Pediatri s: T ilv. 1907. p. 490 liriti h .\le.l. and Si re. J nrr .: \oI. CL> THE TREATMENT OF WOUNDS. WITH REFERENCE TO TETANUS PROPHYLAXIS.* Oscar Berghausen. P.. A., M.D. and Chari.es E. HinvAKn, M. D. Receiving Pli\ sician at the Cincinnati Hospital. Cincinnati. In June, 1910, the late Dr. N. P. Dandridge proposed the systematic handling of all wounds, punctured, penetrating or lacerated, with the aim of ascertaining the best methods of treating such cases at a large general hos- pital, particularly with reference to tetanus prophylaxis. As is well known, to avoid the development of tetanus we must begin by treating, in a thorough surgical manner, the wound received. The use of antitetanic serum as a prophylactic agent was resorted to in a large series of cases, in order to test its value. The following list of instruction.s were placed in eacli surgical ward : The interns will please carry out the instructions mentioned below for the follow- ing classes of cases : 1. All perforating, penetrating or lacerating wounds contaminated directly hy soil or manure, especially those contracted in the streets or about stables. 2. All blank-cartridge and giant-cracker perforating and lacerating wounds. INSTRUCTIONS. 1. In all cases above mentioned remove the clothing and foreign material about the wound. 2. Cleanse the surrounding parts with green soap, alcohol, ether and sterile water. .■?. Remove with sterile forceps any foreign material lying superlicially in the wound. 4. Cleanse the wound with S per cent phenol (carbolic acid) -0.5 per cent hydro- chloric acid solution. 5. Enlarge the opening by free incision if necessary to thoroughly cleanse the wound, or for the removal of foreign substance. 6. Use a general anesthetic whenever indicated. 7. Pack the wound lightly with gauze soaked in the phenol-hydrochloric acid solu- tion, and dress. Change the dressings daily. 8. Immediately after dressing the wound on the first day give 1.500 units of anti- tetanic serum subcutaneously. This serum can be obtained at the laboratory. 9. A careful record must be kept and sent to the laboratory when the patient is discharged. 10. In the case of doubt or on the appearance of symptoms resembling tetanu.-.. notify me [Berghausen] at once. , Heretofore such injuries were opened, cleaned and treated with strong phenol solution. The object of using the hydrochloric-phenol mixture as recommended in the text-books was to test its efficiency, since it is attended by less necrosis of tissue. Experience has shown us that treatment of all wounds after the above fashion was sufficient. Particular care was taken to clean out all wounds thoroughly, opening by incision if necessary, to remove all foreign material. Particularly is this necessary in blank-cartridge wounds when wads may have entered. In such cases, in two instances, wads were removed on successive days by dififerent interns, each one thinking that he OSCAR B ERG HAU SEN AND CHARLES E. HOWARD had removed the last wad. In these cases a general anesthetic may become necessary. To ascertain how many wads were present in each blank cartridge, four different s|ieciniens were bought and examined. In each one two wads were found, but these were found to be rather loosely made and could easily be torn into fragments. AXTITETAXIC SERUM AS A PROPHYLACTIC MEASURE. Owning to the experience of others, we have used only one injection of 1,500 units, usually given in that part of the anatomy nearest the wound. \\'e repeated the injection in three cases in which suppuration persisted. In this connection we wish to quote the results of Sir D. Semple,^ who says : Many people in apparently good health harbar spores of tetanus in healed wounds or in the intestinal tract, and that hidden away in the tissues the spores remain alive and retain their virulence, but do not grow into toxin-producing bacilli. . . . The leukocytes do not always destroy the spores, but when a local suppuration has ceased they may be able to wander away with the spores still in them. . . . Spore-carriers are in danger of suffering from tetanus (a) on the occurrence of great fatigue or exposure to heat or cold, which diminish their resistance; (b) when the site where the spores are lodged becomes converted into a medium, which from being anaerobic and from a failure of phagocytosis, is favorable for the growth of the spores into toxin- producing bacilli: and (c) when a focus of dead tissue forms in a part of the body at a distance from the site where the spores are lodged. Quinin given hypodermatically may produce a local tissue necrosis ; solu- ble non-irritating substances do not. Scmple further ,i>^erts that from 10 to 15 cc. of antitetanic serum renders a patient pa^si\•c■lv immune for a period of from two to three weeks, and has found it a valuable prophylactic agent when using quinin hypodermatically. TABLE 1. CASES IX WHICH SERUM WAS USED PKOPHVLACTICALLV ; GOOD RESULTS. Total Xo. Serum Used, Character of Injury, of Cases in Units Punctured wounds (inostly made by nails) 71 15(X) Contused and lacerated 4 1500 Cannon-cracker wounds 2 1500 C.un-shot wounds 6 1500 Blank-cartridge wounds 7 1500 Powder burns 5 1500 96 SERUM UEACTIOXS. These were noted in several cases and were marked by local redness, swelling, urticaria-like eruptions and fever. Owing to patients not reporting as directed, we were unable to obtain complete statistics in this regard. With the aim of preventing such symptoms or of ameliorating them when once developed, atropin sulphate (gr. 1/100-1/120 three times a day, in children less) was given hypodermatically, particularly when numerous injections of serum were made in cases of developed tetanus. We have found that this drug possesses undoubted value in preventing such symptoms. Itching, red- ness and urticarial eruptions frequently disappeared when atropin was 1. Semple, Sir D. : The Relation of Tetanus to the Hypodermic or Intramuscular Injection of Quinin. PaUidism. Simla. January, 1911. No, 2, p. 32. Pmje 1,3 RANSOMOFF MEMORIAL VOLUME given. \\'e therefore adopted this measure as a routine before all repeated injections of serum. At times such eruptions will appear following the use of ati-opin sulphate, but never to a very marked degree. In Table 1 will he found a list of cases of patients treated at the hos])ital with the aim of preventing tetanus after the method descrilx-d in the fore- going. Not one case of tetanus developed in the above series of patients. In Table 2 will be found those ca.ses in which serum was not used as a |)rophylactic measure, and in which the local treatment of the wound was good. Of this list not one developed tetanus. TABLE 2. CASES IN WHICH SERUM WAS NOT USED PROPHV- LACTICALLY: GOOD RESULTS. Character of Injury No. Cases Result Punctured wound — nail ?> ( lOod Blank-cartridge ?> Cmod 6 In Table 3 will be found those cases in which serum was not used as a ]irophylactic measure, and which later developed tetanus. These patients were first seen by us after tetanus had developed, except- ing cases 1 and 6. Case 7 occurred in the private practice of Dr. George Krieger. of Madisonville, by whom we were consulted and to whom we are indebted. Case 5 occurred in the service of Dr. Casper Hegner at the City Hospital. Two cases in which serum was used prophylactically, the one caused by a cannon-cracker wound of the neck and followed by extreme cellulitis before admission ; the other, caused by stepping on a nail and followed by cellulitis before admission, resulted in sudden death. No autopsy could be secured, but death was evidently due to an enibcilus, no symi)toms of tetanus de\elo]iing and no anaphylactic phenomena. RESULTS WITH AND WITHOUT PROPHYLACTIC SERU.M TREATMENT. In the ninety-six cases properly treated locally and by the prophylactic administration of antitetanic serum, not one patient developed tetanus. In the fourteen cases (Tables 2 and 3) treated without the i)rophylactic administration of antitetanic serum, eight patients developed tetanus, of whom six died. In the cases (only six, however) ])roperly treated locally and without the pro])h\ lactic administration of antitetanic serum, not one ]>atient develo])ed tetanus. Patient 6 ( Table 3 ) was thoroughly treated locally, but did not receive the prophylactic serum injection and succumbed to tetanus. We had the oi>i)ortunity of assisting in the treatment ;>■ i.:-'o (Ian. I 1919; Bull. Johns Hopkins Hosp. 30:29 (Feb.) 1919. RAXSOHOFF MEMORIAL VOLUME livdrocephalus could be made, both of wliich are essential for successful treatment In the present study I have carried out the phenolsulphonephthalein test- in patients with meningitis in which hydrocephalus has developed, and I have had roentgenograms made after the injection of the ventricles with air.'' Particular attention has been paid to the early diagnosis of hydro- cephalus and to the pathologic findings. Twenty-five cases of hydrocephalus were studied. Meningitis due to the streptococcus, the Stal'hylococcus aureus, the influ- enza bacillus and the pneumococcus is a terminal manifestation in the majority of instances, secondary to a primary focus elsewhere. The entire course of the meningitis is usually of short duration, w-hich explains the infrequency of hydrocephalus in meningitis due to these organisms. Hydro- cephalus was observed, however, in the course of a meningitis due to the influenza bacillus in two patients, four and eight months of age, respec- tively. They lived about two weeks. A communicating hydrocephalus was demonstrated at necropsy in one patient, and an obstructive hydrocephalus in the other. In the latter, the hydrocephalus was suspected, as it was impossible to obtain more than a few drops of cerebrospinal fluid by lumbar puncture. The phenolsulphonephthalein test showed that an obstruction existed between the ventricular and the subarachnoid systems, and at necropsy the basal foramina were found to be obstructed by a thick purulent exudate The infre(|uency of hydrocephalus in tuberculous meningitis is due, probably, to the relatively slight involvement of the meninges. It is only occasionally that the exudate is so situated or sufliciently large in amount to interfere with the avenues of exit of the cerebrospinal fluid from the ventricles or to diminish the absorption from the subarachnoid space by involving the cisternae at the base of the brain. In tuberculous meningitis two cases of communicating hydrocephalus were demonstrated. In each patient phenolsulphonephthalein appeared promptly in the lumbar sub- arachnoid space after its introduction into the lateral ventricle, but absorp- tion from the subarachnoid space was greatly diminished. At the necropsy the basal foramina were found to be patent, but absorption was limited to the spinal subarachnoid space by an exudate involving the cisternae. In four cases the hydrocephalus was of the obstructive tyi)e. In these patients, phenolsulphonephthalein did not appear in the lumbar subarachnoid space after its injection into the ventricles. The foramina of exit at the base of the brain were obliterated by a tuberculous exudate in these cases. The majority of the cases of hydrocephalus occurred in meningococcus meningitis. Of twenty-five cases occurring in the course of acute meningitis, seventeen were due to the meningococcus. Communicating hydrocephalus 2. Dandv. W. E.. and Bl.-irkf.nn. K. D. : t .\m. I)i*. Child. 8:-10(. (.\,.v.) 19U; U:.|.'4 (Dec.) 1917. 3. T wish lo rxprcss my Ihniiks to Hi. Walter Dandv and to the staff of the Uepartment of RorntEenology for thfir assistance in makint; the roentgenograms. Page .'iS KENNETH D. BLACKFAN developed in eight of the seventeen cases, and in nine the obstructive form was found. 'Pen of the seventeen patients in this series died and seven recovered, 'i'wo of the seven patients had an obstructive hydrocephakis and improvement followed pr(.)mptly after the introduction of antimeningo- coccus serum into the ventricles. In four cases in which a communicating hydrocephalus was present, the process became arrested after treatment. The patients made an imeventful recovery. One patient developed a chronic hydrocephalus (communicating). He was three months old and was first seen twenty-four hours after the onset of the meningeal symptoms. Men- ingococci were grown from the blood and the cerebrospinal fluid. Anri- nieningococcus serum was administered intravenously and into the lumbar subarachnoid space. After the first few days the meningococci disappeared for ;i time from the cerebrospinal fluid. The temperature remained irregu- lar. The meningeal symptoms did not disappear, and from time to time, in s|)ite of treatment, the organisms would reappear in the cerebrospinal fluid, lie was treated intensively with serum introduced into the ventricles and the hunljar subarachnoid space o\er a jieriod of twenty-four days before the meningococci disajipeared permanently and the cerebrospinal fluid became normal. Seven months after the onset of the meningitis, the head was greatly enlarged and a ventriculogram showed almost complete destruction of the cortex (Fig. 1). The patient is alive at the present writing. A necrop.sy was performed in the ten fatal cases, and the clinical diag- nosis was confirmed by demonstration of the exciting cause of the hydro- cephalus. In seven cases (obstructive hydrocephalus) an exudate occluded the foramina at the base of the brain, and in three cases (communicating hydrocephalus ) the basal cistemae were totally obliterated by a thick puru- lent exudate. Whether an exudate or adhesions are found at necropsy in this form of meningitis depends primarily on the duration of the disease. It is not within the province of this paper to discuss the pathologic pro- cess met with in the various types of meningitis. Acute hydrocephalus in meningitis develops because, as in chronic hydrocephalus, there is a diminu- tion in the absorption of the cerebrospinal fluid. The important point to recognize is that the lesion must be so located as to obstruct the outflow of cerebrospinal fluid from the ventricles to the subarachnoid space, or else to limit the area of absorption from the spinal or cerebral subarachnoid system. The disappearance of the exudate and the formation of adhesions determine the transition from an acute to a chronic hydrocephalus, and the re-establishment of an ec[uilibrium between the formation of cerebrospinal fluid and its absorption determines whether the process will become arrested or advance progressively. The chronicity of meningococcus meningitis makes it the form of meningitis ]iar excellence for the development of a chronic hydrocephalus. Meningitis due to other organisms almost without exception is fatal, and in a short time. Page .}.■) RAXSOHOFF MEMORIAL VOLUME Fig. 1. Roentgenogram taken seven months after the onset of an acute attack of meningococcus meningitis. The phenolsulphonephthalein test showed that there was a free communication between the ventricles and the spinal subarachnoid space. Ab- sorption from the subarachnoid space was 9 per cent, in two hours. After air injection the roentgenogram showed the lateral ventricles to be markedly dilated (A) and an extreme grade of atrophy of the cortex (C). TABLE 1. ACUTE HYDROCEPHALUS IN MENINGITIS. Type of Meningitis No. of Cases of Meningitis with Hydrocephalus Studied 2 17 Type of Hydrocephalus Obstructive Communicating 9 a Total 25 ]] Attention may be directed to a hydrocephalus developing in meningitis by the onset of certain symptoms. The diagnosis is readily established when the condition is of long duration and the symptoms of increased intra- cranial pressure — headache, stupor, vomiting, enlargement of the head and changes in the eye grounds — are present. The early manifestations of hydrocephalus, however, are so closely interwoven with the symptoms of the meningitis itself, that they are often difficult to recognize. Hydro- cephalus should always be suspected with the persistence of symptoms of meningeal irritation (fever, hyperesthesia, irritability or drowsiness, rigid- ity of the muscles of the neck and extremities, hyperactive reflexes, tremors, etc.) or their reappearance after the symptoms of meningitis have subsided. Infants invariably have a tense and bulging fontanel and in children. Mac- Pagc SO KEVNETH D. BLACKFAN ewen's sign is positive. It should be remembered that these symptoms can- not always be referred to the hydrocephalus alone. We often see at the onset of acute meningitis and throughout the course of the disease manifes- tations indicative of increased intracranial pressure — headache, fever, vom- iting and muscular rii^'idity- which do not mean necessarily that hydro- cephalus is present. I believe that much confusion has been caused by refer- ring to such a condition as hydrocephalus. For instance, in tuberculous meningitis there is present quite constantly a marked increase in the amount of cerebrospinal fluid, but at necropsy a picture quite the reverse of that seen in hydrocephalus is found. The sulci are distended with fluid, the brain is edematous, and though there is a varying increase in the size of the ven- tricles, one does not find flattening of the convolutions, atrophy and com- pression of the brain substance and the marked dilatation of the ventricles which characterize the latter condition. A number of patients with tuber- culous and meningococcus meningitis who presented such symptoms have been studied by determining the amount of cerebrospinal fluid withdrawn, by the phenolsulphonephthalein test and the pathologic findings at necropsy. In these patients there was no interference with the absorption of cere- brospinal fluid and at necro])sy the findings characteristic of hydrocei)halus were not present. It is not at all likely that an increase in the amount of cerebrospinal fluid can produce other than a temporary and insignificant hydrocephalus, unless there is an associated diminution in the absorption of the fluid. The results are shown in Table 2. Abnormal changes in the eye grounds and enlargement of the head, when present, are symptoms indicative of an hydrocephalus, but they are seldom seen early in its development and so are of but little aid in making the diagnosis. This is especially true before the fontanels are closed and the T.\BLE 2. FINDINGS IN CASES OF MENINGITIS WITH INCREASED INTRACRANIAL PRESSURE, BUT NO HYDROCEPHALUS. Phenolsaiphonepthalcin Spinal Fluid CaFe Diagnosis Absorption from Sub- arachnoid, per cent. Patency of Comnnmi- Pressure .^mount C.c. Necropsy Tuberculous 45 10 Increased 40 Ventricles not dilated. Exu- date slight, not involving the Tuberculous 4(1 12 Increased 55 Ventricles not dilated. Exu- meningitis date slight, not involving the basal foramina or risternae. Tuberculous meningitis J8 ' Increased 35 Ventrn I.- ..-< A.'.uA Exu- dal. -• ■ ■ ■. Uing the Tuberculous meningitis 42 " Increased 45 Vcnliu:. 1, ■ .:: /..I Exu- datf -l.L-:l, . ,.' r:^..lv,nc tlie basal fnramn,,, .., M-.,,n,,r Meningococcus 55 12 Increased dO V^entricles not .i,-.,i..l l-n meningitis date slight, HM, ,:,^,,l,n:, ,li, basal foraniin. ,.ir,„,„' " Meningococcus 48 in Increased 40 Ventri.-I.- ."1 .'■■ ',.1 Ivvn- dat,. ^Im.l. ,:,,, ,. ,,,'>„,g the bas;.l t, . i^u-rnae. meningitis 45 Venln. ;. i : i ...,l Exu- basal foramina or cisternae. RANSOHOFf MEMORIAL J'OLUME sutures are firmly united. A considerable atroiih)- and compression of the brain takes place before the intraventricular pressure becomes sufficient to cause marked changes in the eye grounds and an enlargement of the head. This is well illustrated in the case of an infant, three months of age. who was observed from the onset of an acute meningococcus meningitis throughout the various stages of development from an acute to a chronic hydrocephalus. This is graphically shown in Table 3. Table 3. FINDIXGS IX A CASE OF ACUTE MEXIXGOCOCCUS MEXIXGITI.S DEVELOPIXG FROM AX ACUTE TO A CHROXIC HYDROCEPHALUS. duration of ference Disease of Head Com- (from Si.h- munica- arachnoid tion ' Space Collapse, fever, de- pressed fontanel, petechiae. liulpinK fontanel, rigidity, hyperes- Slight dilatation Ventricles >f retinal vessels, dilated. Afarked Margin of disk I cortical clear. | atrophy. , Normal physi- ologic cupping. Same Same Ventricles greatly enlarged. Bulging fontanels, separation of su- tures, craniotabes, rigidity, vomiting, The amount of cerebrospinal fluid obtained by lumbar puncture afTords the most helpful clinical sign of hydrocephalus, although, as previously mentioned, it is not absolutely dependable. In hydrocephalus the cerebro- spinal fluid is under greatly increased pressure and an abnormal amount is obtained readily or it is obtained in small amount and with difficulty. A definite increase in the amount of cerebrospinal fluid of 50 cc. or more, withdrawn repeatedly when the other signs of the acute infection of the meninges have subsided, is significant of a communicating hydrocephalus. While this is suggestive evidence, it is not sufficient in itself to establish the diagnosis, as relatively large amounts of cerebrospinal fluid are sometimes found in obstructive hydrocephalus. Small amounts of cerebrospinal fluid obtained by lumbar puncture sug- gest an obstructive hydrocephalus. If the subarachnoid space has been entered, and the fluid is not too thick to run through the needle, it is rela- tively safe to conclude that there is an exudate so situated as to prevent the free flow of cerebrospinal fluid from the ventricles to the spinal subarachnoid space. In obstructive hydrocephalus relatively large amount of cerebro- Pagc 52 KENNETH D. BEACKFAN spinal fluid may be recovered at tlie first lumbar puncture and then the quantity lessens so that only a few drops are obtained at successive punc- tures (Fig. 2). Corroborative evidence of the presence of hydrocephalus Fig. 2. Obstructive lijdroceplialus in a patient aged three months. The onset of the hydrocephakis was suggested ))>■ the persistence of the s5mptoms of meningitis. The cerebrospinal fluid was obtamed reaUiK for ten da>s and then only a few drops flowed from the needle. The plun. ilsiil|ih.>n( plilh.iKni test slicwi-d that tlit-re was no communication between the \cntn. 1.^ .mil ili, miK.it. u hn. iid -.p. hi.-. ,\1is. niuion from the subarachnoid space was 55 pci n_iu m tu.i horns \iur .ui mjcction tlu' roentgen- ogram showed dilated lateral \(.ntiKli, ( \\ with ,ili..pln <.l Uie cortex (Cj. may be shown by the results from puncture of the ventricle, as in such cases the cerebrospinal fluid in the ventricles is under increased pressure and an excessive amount can be withdrawn. 'i'he early recognition of hydrocephalus is of practical importance in meningitis due to the ineningococcus. Many cases of hydrocephalus, the result of meningococcus meningitis, are reported in the literature in which the hydrocephalus developed despite treatment with antimeningococcus serum. In the majority of instances this has occurred when treatment was instituted late, for the outcome at this stage of the disease, even with appro- Pmje M RANSOnOfl- MEMORIAL I'OLUMR in-iale treatment is uncertain (Fig. 3). The earlier and tlie more intensive the treatment, the better the chance of recovery. In obstructive hydro- cephahis if the serum is introduced only by lumbar subarachnoid injection there is the danger of organization of the exudate and also that the meningo- cocci remaining in the ventricles are not subjected to the influence of the serum. In this form of hvdroceiihalus the antimeningococcus serum should l)e inJL-clud dircctlv into ihe ventricle as well as into the lumbar subarachnoid (lildttd \entlicks li.ttitiit ditd in s]ii lIl-s ami intd tilt- ,1 patiiiit. twii years old, wlio was un- Mi .i| an a. utc meningococcus meningitis. P i-.iii\, Kruno's sign and a low grade optic 1 -li v\(.l ilial there was a free communica- hiMid -.iiaii', .Misorption from the subarach- \ttcr air injection the roentgenogram showed umpression of the cerebral cortex (C). The of antimeningococcus serum into the ventri- space. In communicating hydrocephalus intraventricular injection of serum also is advisable. A larger amount inay be injected -imd thereby brought into direct contact with the exudate and in greater conceiUration than by the lumbar subarachnoid injection alone. (Fig. 4.) The capacity of the meninges to absorb cerebrospinal fluid should be tested by the lumbar subarachnoid injection of phenolsulphonephthalein, when the symptoms of meningeal irritation persist or when they reappear after the vigorous use of antimeningococcus serum. A distinct diminution in the absorption of cerebrospinal fluid indicates a comnuinicating hydro- Pagc r,l, KENNETH D. BLACKFAN cephalus. This diagnosis can be confirmed by determining the patency of the foramina between the ventricular and the subarachnoid systems by the injection of phenolsulphonephthalein directly into the ventricle. If the symptoms are the result of an obstructive hydrocephalus the absorption of the cerebrospinal fluid from the luniljar subarachnoid space will not be Fig. 4. The patient, aged three v.ii--, w.i ingocdccus .serum. He did not ini|ii.iM .md spinal fluid. The plienolsulphonephth.iK m dsi arachnoid space was diminished (1,? pc i nut i the dye througli a trephine opening cliiimnsti . tricles and the himbar subarachnoid space, shows enlarged lateral ventricles (.AX the tre[: atrophy of the eerebralcorte.x (C). .Xfter thre into the ventricles, the organisms disappear .\fter air injection the roentgenogram hine opening (B) and compression and ■ injections of antimeningococcus serum -d. The patient made an uneventful diminished. The diagnosis in this type of hydrocephalus will then (lei)end on the nonappearance of phenolsulphonephthalein in the lumbar subarach- noid space after its injection into the ventricle. These tests add nothing to the severity of the treatment. They do not demand any unnecessary opera- tive procedure, as under such circumstances it is necessary to bring serum, either through an open fontanel or through a trephine oi)ening, in so large an amount and in as concentrated a form as possible, directly in contact with the purulent exudate at the base of the brain. STANDARDS OF SUCCESS IX .MEDICINE.* George Emerson Brewer. In accepting the invitalioii of our President to be present at the annual opening exercises of the medical school and say a few words to the enter- ing class, I was somewhat at a loss to determine what subject I should choose which might be of interest. I take it, that in an address of this kind an effort should be made to suggest some thoughts which will be helpful to the entering student in arranging his time and studies or informulating plans for his future work, and in addition to remind him of the responsi- bilities which he is to assume, the difficulties he will encounter, and the kind of success he may hope to attain. -As I look about me and study for a moment the new and unfamiliar faces, differing as they do in many respects and conveying to my mind dif- ferences in character, temperament, jjrevious training, and the ability to work. I feel that they express one thing in common, namely, a determination to begin in earnest the real business of life. In the preparatory schools and colleges your intellectual burdens have been lightened by a judicious admix- ture of recreation, sport, and mutual companionship; you have enjoyed long periods of vacation, and at no time have been driven under high pressure toward the attainment of a single object, upon which will depend the meas- ure of your success in life. Here in the medical school all will be changed: you will find conditions materially altered, you will be surrounded by an atmosphere surcharged with enthusiasm and active competition. Soon you will realize that to win a prize or even to receive an honorable mention in the jirofessional race with your colleagues, you must at least secure at the end of your college course a creditable hospital appointment. To obtain this you must early acquire and persistently maintain a high rank in your class, and this means hard, enduring, concentrated work, not a few hours each day, but from ten to twelve or fourteen hours out of each twenty-four of the college year, and the willingness to devote at least one-third to one- half of your summer vacations to clinical work in the various hospitals and dispensaries of the city. If these conditions seem too severe, better matric- ulate at once in some other medical school, for here at the College of Physi- cians and Surgeons our standards are high, our student body far above the average in intelligence and training, and the pace set by the leaders of each class exceedingly difificult to maintain, but we firmly belie\e that the rewards open to the successful student are well worth the effort. This thought suggests the inquiry why so many young men, well equipped for almost any professional or business career, choose annually to cast their lot with the medical fraternity. It is certainly not with any hope of amass- ing a fortune, for if you do not already know it. it is only fair for me to '.Address delivered .-il tlie npenine exercises at the Collece of Plivsici.ins .ind Surgeons, Sei)t ber 24. 1913. I-roiii The Cohimbia University Quarterly. .Mar.. 191-1. Page SO GEORGE EMERSON BREWER assure yon that the practice of medicine offers little or no hope of great financial return. What, then are the rewards of a life devoted to tlie study and practice of medicine? \Miat are the reasons why you have elected to devote your lives to a profession which oft'ers so little of pecuniary reward even to the most successful of its followers? I take it that the reason why so many capable young men enter our profession is that they hope for and expect a reward which cannot be reckoned in dollars and cents, but which will out- weigh in real value the benefits to be derived from the accumulation e\-en of great wealth. This brings me to the announced subject of my informal talk with you this morning: What are the standards of success open to the practitioner or student of medicine? Time will permit me to mention only a few, and these I can best illustrate by examples. Take in the first place the practi- tioner of internal medicine, the man whose relationship to his patient is that of the family physician. Those of you who are familiar with the charming essays and character sketches of Maclaren, will recognize as one of the best of this type, the rugged resourceful old Scotch physician, William MacLure, a doctor of the old school, wlio preferred to practice his profession in the highland glen of his birth to accepting an honorable position in one of the great medical centers. For forty years, day and night, summer and winter, in sunshine and storm, through snow, ice, drifts and floods, he visited the sick and injured of his own village and the scattered dwellers of the glen. It is true, MacLure was but a character of fiction, created as a composite type from the lives and virtues of hundreds of his class in all parts of the civilized world — the type of man who gives. all that he possesses in kindli- ness, sympathy, and helpful assistance for a lifetime, and receives in return only sufficient coin of the realm to keep a roof, over his head, food and clothing for his body, but such a harvest of esteem, appreciation, gratitude and affection, as to fill to overflowing every desire of his generous heart. Let us, however, turn from the hard conditions of life of our rugged Highland practitioner, to the softer paths of one of his more fortunate lirotliers. I have in mind the career of one of the greatest consultants and teachers of medicine of our times. Reared amid scholarly surroundings, graduating in medicine at an early age, he quickly rose to a commanding l)osition in the medical world. The master word of his early training seemed to be work : constant, conscientious, concentrated, and systematic work. By this means he early acquired an enormous fund of medical knowl- edge, and in addition so trained his mind to accurate observation, accurate deduction, and accurate speech, as to fit himself admirably for the role of teacher, in which he later became so successful. To watch him on his hos- pital visits was a liberal education ; the carefully elicited history, the accurate and painstaking physical examination, the judicious employment of labora- tory aids, and finally the logical summing up of the evidence, his masterly Page 57 RANSOHOfF MEMORIAL rOLUME analysis of the symptoms and signs of the disease leading to the establish- ment of an accurate diagnosis, as well as his safe and sane suggestion in regard to treatment, made him one of the great clinicians of his time. The sterling qualities of his mind, his great industry, his charming personality, his magnetic enthusiasm and withal his keen sense of humor, would have made him a conspicuous success in any walk of life or field of human en- deavor. In medicine few if any practitioners ever reached the measure of professional success which he achieved ; and no teacher ever inspired in his students more lofty ideals, more enthusiastic devotion to work, or more loyal affection for their chief. William Osier never prized, sought after, or accumulated wealth. He always preferred an autopsy to a consultation, and almost invariably would refuse an out-of-town summons from a wealthy client if it interfered with his hospital rounds or a morning with the stu- dents. In his mental and moral make-up, there was never any suggestion of commercialism, yet his professional success was so great as completely to overshadow any thought of financial reward. It is perhaps the general surgeon whom the world looks upon as reaping the highest financial rewards in the medical profession, and yet one seldom hears of a surgeon who.se period of large returns lasts more than a few years. Of all the surgeons of my acquaintance, the one whose life .semed to himself and his associates most rounded and filled with professional satisfaction and success, was a man born amid the humblest of surroundings in a small New England hamlet. With educational opportunities of the most limited char- acter, by extraordinary industry, undaunted courage, and an unlimited capac- ity for work, he raised himself to one of the foremost position in surgery of his time. Cast in a heroic moHld. with fine constitution and superb health, he began his practice in a western city, and learned his surgery by hard per- sonal experience. Receiving his degree long before the antiseptic era. he, in common with all others practicing surgery at that time, soon became familiar with the almost universal septic disasters which followed surgical operations, and yet by keen judgment and by an almost superhuman surgical intuition, he seemed to avoid in a remarkable degree the fatalities which fol- lowed the work of others. His success inspired wide confidence, and as a result of his sterling integrity, kindly manner and great-hearted sympathy, the members of the community in which he lived, almost without exception, turned to him in their surgical emergencies. No operation offering a rea- sonable ho]ie of success was too difficult for him to undertake; no sacrifice was too great for him to assume, if it contributed to the well-being or com- fort of his patient ; and no man or woman was too poor to insure his best efTorts. His talents were soon recognized, and while still a young man he was appointed professor of surgery in a flourishing medical school. His reputation grew rapidly, his skill was constantly in demand, by the rich and poor alike, not only of his own city, but throughout the greater part of his own and neighboring states. His contributions to abdominal surgery, then GEORGE EMERSON BREWER in its infancy, his improvements in operative technic, and his ingenuity in devising new and improved methods of operating and wound treatment gave him a national reputation. I never knew a man whose life was so full of anxious work ; his expenditure of energy would quickly have disabled a man of less vigorous constitution. Although he enjoyed for his day a large income from his wealthy patients, more than half his time and efifort was devoted to the less fortunate members of society, from^-^'hom he received little or no compensation. One day in the height of his professional success, he was called upon by a physician of his acquaintance who asked him if he would operate upon a man with strangulated hernia. He explained (hat it was impossible on account of a college lecture and an afternoon filled with appointments and urgent consultations. His colleague replied that it was unfortunate for the jjatient, who refused to go to a hospital or allow any one else to o]ierate. The surgeon hesitated, then inquired if the man had money. "No," was the reply, "only an invalid wife and a large family of children." "Then I will go," was the reply ; "poor devil, if he had money he could get some one else." Quickly canceling his engagements, he gath- ered his assistants, went to the poor man's home, and performed a successful operation. In performing the operation, successful for the patient, the operator accidentally pricked his finger with a needle. That needle-prick ended the career of this talented great-hearted surgeon — not by a (|uickly fatal infection with moderate suffering, but by a long-drawn-out, discour- aging and progressively weakening malady ; for the virus entering the veins by this insignificant needle prick was the venom of syphilis. Occurring at a time when the disease was little understood, and treated with less success than at present, with the kindly assistance of his professional colleagues he battled with the virulent infection for weeks, months and years, only to develop at the end the gravest type of cerebral disease. He died a mental and physical wreck. You may ask why I mention the career of this unfor- tunate man as an example of professional success. I mention it not only on account of his valualile contributions to surgery for twenty-five years, but chiefly for the reason that every act of his generous life was, like the imme- diate cause of his untimely death, inspired by an unmeasured aiuount of human sympathy and love for his fellowmen. Before closing I feel that I must say just a word in regard to the oppor- tunities for professional success offered by the laboratory worker, the investigator, the seeker after the great truths which nature seems so maliciously to conceal. The poorest paid of all, this unselfish and self- sacrificing army of scientific workers seems content, without hope or thought of pecuniary reward, to devote their lives to the study of the nature and causation of disease, the etiology of infection, the pathology of new-growths, the underlying principles of immunity, the function of the ductless glands, the synthetic elaboration of remedial agents, the explanation of shock, the development of new and safer methods of anesthesia, surgical technic and RAXSOHOFf MEMORIAL r GLUME the hundred other problems of vital interest to the practitioner. The work is arduous, lime consuming, exhausting, yet the rewards are great. Take the life of Jenner, the English country doctor, living in the last century at a time when the great civilized centers of Europe were annually devastated by the most dreaded of all modern plagues, epidemic .smallpox. He made up his niind to investigate its cause and, if ])ossible, to discover a remedy for it. He began to study it carefully from all points of view, and his attention by a strange coincidence was quickly directed to a similar disease which prevailed among cattle. Mildly toxic in character, it was accompanied by lesions which were almost identical with those of smallpox. Dr. Jenner also discovered that the people who had care of these cattle, as milkmen and stablemen, were often infected and presented small lesions on their hands, and that these people were absolutely and forever immune from smallpox. Then a great idea entered his mind: if the entire community could be inoculated with this mild cowpox, no epidemic of smallpox could afTect them. This idea grew in the mind of Jenner, and developed into a great principle of medical therapeutics, ^^'hen he was bold enough to an- nounce his discovery before the Royal College of Physicians of London, did they receive it with enthusiastic interest or open minds: Not at all — on the contrary, they denounced Dr. Jeimcr, called him a quack, a charlatan, declared that his methods were brutal and inhuman and should never be included in scientific medical jjractice. Jenner. however, jiersisted in advo- cating protective vaccination, and was finally enabled to ]irove the truth of his discoveries. He died a poor man. Although he de\ oted the greater part of his professional life to this great work, if it had not been for the liber- ality of the British government he would have died in abject poverty. Today what millionaire, what multimillionaire, would not give the greater part of his possessions for a name and fame like that of the great Jenner? Let us turn for a moment to the career of Pasteur, a trained chemist, who in early life gave evidence of great originality of thought. Pasteur thought he saw in fermentation the action of living germs, low forms of animal and vegetable life. As he studied fermentation, he actually discov- ered in fermenting substances millions of these organisms, dififering ifi size and shape with the various types of fermentation. Later he recognized that the processes he observed during the fermentation of inert matter were similar to the processes which take place in human beings and animals as a result of infectious disease. Then a great idea occurred to him, namely, that these or similar micro-organisms were the cause of infectious diseases. By his logical reasoning, his accurate methods of investigation, and his epoch- making inoculative experiments, he demonstrated the great truth of the causation of contagious diseases, namely, that they are due to the presence in the blood and tissues of these low forms of animal or vegetable life — and the great germ theory of disease was born. As a reward, did Dr. Pasteur receive the generous treatment of his medical colleagues? Decidedly not. Page SO GEORGE EMERSON BREWER He was more bitterly denounced and criticized than was Jenner; but he knew he was right because his methods were accurate ; he was convinced that his logical deductions could not be disproven, and he finally was able to demonstrate to the scientific world that his theories were absolutely cor- rect, ( )n the occasion of the celebration given in honor of his seventieth birthday by the French government, before an enormous audience com- l)Osed of distinguished men of science from all parts of the civilized world, the great Lister, addressing him, said: "You have raised the veil which for centuries has covered infectious diseases. You have discovered and demonstrated their microbic origin." Dupuy, a colleague, said: "\\*ho can say how much human life owes to you, and how much more it will owe to you in the future." J. I'.. Dumas, his friend and admirer, said: "Alay I'rovidence long spare yuu to France, and maintain in you the admirable equilibrium between the mind that observes, the genius that conceives, and the hand that executes with a perfection and accuracy hitherto unknown." Apart from his epoch-making discoveries. Pasteur blazed the trail for all future investigation by demonstrating the immense value of painstaking accurate laboratory methods in the elucidation of the many biological and pathological problems which have confronted and which are today con- fronting the medical world. As a result of the powerful stimulus given to all scientific work by his methods and success, and the many problems sug- gested by his demonstration of the microbic nature of infectious diseases, hundreds of able workers have been attracted to this fruitful field of investi- gation, and medicine has been enriched by the masterly work of Koch, of Roux, of Behring, of Kitasato, of Ehrlich. of W'idal, of \\'right, of Welsh, of Flexner, and a host of others equally distinguished. It is, however, to the work of Lister that surgeons turn with sui)crlativc pride and with the greatest satisfaction. Practicing surgery in the jire- antiseptic days, he quickly appreciated thai the greatest factor in the pre- vention of surgical progress was infection — not at that time known by that name or understood, but recognized on every side by its final results, sup- puration, wound fever, pyemia, septicaemia, erysipelas, hospital gangrene, etc., etc. The death rate from this cause following surgical procedures was so great, that only a few necessary life-saving operations were undertaken, as the repair of severe injuries, amputations for malignant disease, ligation of vessels for hemorrhage or aneurism, and the occasional removal of dis- figuring tumors. The death rate following major amputations was upwards of 60 per cent., of strangulated hernia 40 to fiO per cent., of abdominal sec- lion almost 100 per cent. In not a single instance in one hundred years at the \'ienna Maternity Hospital had a woman survived Csesarean section, an operation }ou will fre(|uently see at the Sloane Hospital with practically no mortality. Nelaton. who was in despair during the siege of Paris, at the sight of the death df nearly every patient operated upon at the Grand Hotel, then a temporary military hospital, declared that the surgeon who could con- RANSOHOFf MEMORIAL VOLUME qiier purulent wound infection would be deserving of a golden statue. Lis- ter's great mind saw in Pasteur's work an explanation of surgical infection. He believed septic disease to be due to the presence in the tissues of patho- genic bacteria, and he conceived the great idea that if those micro- organisms could be excluded, primary healing without fever or other unfa- vorable symptoms would occur. Then followed years of arduous experi- mental work, in which he was hampered and harrassed, not only by pro- fessional criticism and ridicule, but by the action of the British government, which, yielding to the antivivisection clamor, enacted legislation which prac- tically prevented his continuing this great work on English soil. Un- daunted by this hostile action he transported his laboratories to France, and there, amid more favorable conditions, he completed his great work. In giving to the world a method of operating by which sepsis can be avoided. Lister's discovery must be regarded not only as the greatest contribution to surgery of this century, but as the greatest advance in surgical therapeutics of all centuries, the greatest life-saving measure of all time; for it not only removed the terrific death rate of the few operative procedures then em- ployed, but it opened up the vast field of modern surgery, which has resulted in the relief and cure of scores of diseases, which without the aid of modern surgery led only to death, prolonged sufifering. or chronic invalidism. So long as the human race suflfers from injury or surgical disease, so long as surgery is practiced or taught, so long will the name of Lister be known and justly spoken of as one of the greatest benefactors of mankind. Gentlemen, T have attempted in this informal t.nlk to give von an idea of the standards of professional success which m.Tv be attained in addition to the gaining of a livelihood. Not that I would for a moment belittle the latter aim, for the workman in medicine is certainlv worthy of his hire. Rut if vou practice your profession ethically, with intelligence, with skill and with a large measure of human sympathy and philanthronv. you will never receive in dollars and cents anything like an equivalent of the services vou render: yet it lies within the power of each one of you to attain a profes- sional success which will be satisfying directly in proportion to your activities. The profession you have chosen is an honor.nble one. its Iiistory and traditions are inspiring, its accomplishments are deserving of the greatest praise, but to succeed in it you must be prepared to give it your best efiforts, your unceasing devotion, your undivided attention — you must make it in reality your life work. Remember, however, that the path to success is not an easy one: discouragement, failure, and criticism often virulent and unmerited will be vour lot, if vou leave the lieaten track and seek to estab- lish new priiu-iplcs, or advocate methods not sanctioned by tradition. Let Page eg GEORGE EMERSON BREWER me urge )ou, however, in your periods of discouragement and trial to bear ill mind the words of the poet : "One ship drives east and another west, \\'hile the self-same breezes blow. It's the set of the sails and not the gales That bids them where to go. Like the winds of the sea are the ways of the fates, As we voyage on through life; It's the set of the soul tiiat determines the goal. And not the storms and the strife." George Emerson Brewer. MLXTirLE IXFECTIONS. Bv Mark A. Brown. M. D. L'litil within comparatively recent years the presence of two or more infectious processes existing in the same individual at the same time was looked upon with a considerable degree of skepticism to say the least. Whether it was thought that because of the existence of a certain infec- tious disease, a particular antitoxin was introduced or generated within the body that exerted an action antagonistic to the activity of other germs. or what not, I do not presume to say. Indeed, I am not prepared to say that under certain circumstances, among certain germs or infectious processes, this antagonistic action docs not take place; it opens up a field of specula- tion and theorizing too wide for me to attempt here. Aly object to-night is simply to place on record a few cases of multiple infection, cases in which there could he no doubt but that two or more infectious processes were actively at work in the same individual at the same time. In the first place, it must be assumed — and we have all of us accepted it probably long ago — that there are certain diseases which must be classed as infectious, in which no germ has as yet been isolated, that therefore do not conform to Koch's laws, but concerning which there can exist no uncertainty in the minds of those willing to accept the germ theory, but that they are dependent upon a specific organism. I, of course, refer among others to certain of the infec- tious diseases of childhood, to syphilis, and to the disease that brought out that most interesting paper of last ^Tonday night — acute inflammatory rheu- matism. CASE I. SYPHILIS AXD VACCINIA. Patient, a male, aged 28, unmarried, of good physique, well developed and nourished. He was first seen on March 16. 1900. coming to me to be vaccinated. The vaccination "took" in the usual time and began to pass through the usual changes. On the seventh day after the inoculation he came again and called my attention to an eruption that had invaded the sur- face of the body pretty .generally, with the exception of the face. It was present to a slight degree both upon the palms of the hands and the soles of the feet. The eruption was most decidedly of a copper hue, and was not actively inflammatory in type^that is to say. the skin around each indi- vidual lesion was not at all hyperemic. It was distinctly a psoriasis, and this, combined with the marked copper color and the involvement of the hands and feet, led me to the opinion that it was syjjhilitic. Indeed, that was also his idea, for he freelv admitted that lie had had a hard chancre about MARK A. BROWN two years previously, which had been followed by a general cutaneous erup- tion and later by some ulcers in the mouth. He had carried out his treat- ment in rather a desultory manner, but there had been no recurrence of eruption until the present time. He brought up the question, which has since puzzled me, if the vaccination could have caused a flare-up of his syphilis. The pock on his arm pursued the usual course, not severe, and scar forma- tion took place in the usual time. At no time was there any pustular erup- tion present, or, indeed, any other than the psoriasis I have mentioned. He was ordered mercurial inunctions and the eruptions responded immediately, though at the end of two weeks there could still be seen very faint copper- colored stains, CASE II. I'STIVO-.VUTU.MKAL M-\I.-\RIA .\XD PULMOXAKV TUBERCULOSIS. Albert 13., male, aged 25, a native of Tennessee. About two years ago he left the mountains where he had been raised and went to Texas. While there he contracted malaria of rather a severe form, which responded rather slowly to treatment. When not constantly under the influence of quinine the chills and fever would return, so that he was finally advised to return home, which he did. In all he was in Texas nine months. On returning home he improved slowly and steadily until about four months ago, when he began to lose in weight and to suffer from occasional chills, though no actual rigors. He complained mostly of weakness and of severe diarrhea, the latter often accompanied by great abdominal pain. His appetite was capricious ; there were occasional attacks of vomiting. He was finally brought to Cincinnati, and I first saw him at 9:30 a. m.. May 12, 1902. I mention the time of day, as on taking his temperature during the examina- tion that followed it was found to be normal. Particularly manifest was the grave anemia, which, combined with the peculiar lemon-yellow tint of his skin, brought immediately to mind pernicious anemia ; however, with the clear history of malaria given, this opinion was not long entertained, though there is no reason why the two could not exist together, some authorities, indeed, giving malaria as one of the causes of pernicious anemia. The tem- jierature, as has been said, was normal ; the ])ulse about 100, of low tension and markedly dicrotic ; as indications of the anemia, the feet and ankles were markedly edematous. The lungs were not examined at that time, as there was absolutely no history that would lead one to believe that they were involved. A superficial examination of the heart revealed a slight systolic murmur, which was ascribed to the anemia. He was sent at once to the Presbyterian Hospital, with orders as to treatment. .\s I had to leave the city that afternoon I did not see him until the morning of the 14lh, when the first blood examination was made. The blood when drawn from tiie ear showed little tendency to coagulate. Examination of the fresh unstained blood showed the plasmodium of Laveran after about five minutes' search. The first three specimens were quite small, rounded. RAXSOHOFF MEMORIAL VOLUME with most of the pigment at the periphera, no portion of red corpuscle remaining. The jjigment granules were small, hut such as were toward the center showed movement, though sluggish. The fourth specimen was an egg-shaped corpuscle with one pole occupied hy the parasite, in which latter movement of the pigment granules was distinctly \isible. Dr. Oliver and the internes who afterwards examined the slide told me that they had found crescents, which were what I myself had been particularly in search of. There was no poikilocytosis. There was some free pigments in the blood and the few leucocytes seen were markedly pigmented. The diagnosis of estivo-autumnal malaria was made and quinine ordered; the slight effect of the latter treatment can be seen by the most casual inspec- tion of the temperature chart. It will also be noted from the temperature chart that the rise always began about noon and continued throughout the afternoon and evening — hectic, indeed ; while in malaria it has been my experience to have the paroxysm in the morning, though of course this is not always the case. I was satisfied that estivo-autumnal malaria was pres- ent in this case, and malaria of this nature is usually accompanied by a mild continued or slightly remittent fever, or in chronic cases, in which few organisms are present, as in the one under consideration, l)y no fever at all. In this case, too, the rise of temperature was never accompanied by chills. Lastly, there was the total failure of response to ciuinine ; I have always believed the dictum that any intermittent fever which does not in three or four days respond to quinine is not malarial. I knew positively that estivo- MARK A. BROWN autumnal malaria was present — the typical specimens showed that — though it was rather unusual to find the regular intra-corpuscular parasites and the crescents in the same peripheral field ; then, too, as indicated before, one would not expect from the examination of the blood a fever of the type here shown. The natural conclusion was that there was another lesion present that liad been overlooked. It was not hard to find; examination of the left apex of the lung revealed dullness, and immediately under the clavicle, at about its center, was well-marked cavernous breathing. The cavity was quite small. A few mucous rales were present over the left lung, extending to about the fourth rib. Posteriorly these rles could be heard extending to the upper level of the infra-scapular fossse. That was all. surely not enough to account for the great loss of weight — about 60 pounds — and strength, and the pro- found anemia (the blood count was about 2,800,000), all within the space of not over four months. On questioning the nurses in charge, it was learned that he had coughed but rarely, and ex])ectoration, on reference to his spit-cup, occurred but four or five times in the twenty-four hours. I^e himself was so little annoyed by these latter symptoms that he had not thought it worth while to mention them to me. The examination of the sputum revealed tubercle bacilli in large numbers, as well as an abundance of the germs of suppuration. The examination of the urine was entirely negative. The stools were, as a rule, loose, sometimes of a greenish color, and often containing mucous. The liver was markedly enlarged, the s])leen less so. It seems to me, in the explanation of this case, that the lessened vitality caused by the invasion of the plasmodium so lowered bis resisting power that he was unable to withstand the onslaught of the tubercle bacillus, even though assisted by a pure mountain air, good hygienic surroundings, and the best of good country food. This case has been of particular interest to me in \iew of the fact that every year probably thousands of cases of early phthisis are called malaria ; the combination of the two diseases in the same individual is, I believe, a little unusual, at least it is the first case of the kind that has been brought to my attention. I do not believe, in view of the absence of response of fe\Tr to quinine and the few parasites found, that the fever was in any way dependent upon the malarial infection ; the chart shows it to be a typical example of that fever occurring during the first few months of phthisis, the so-called fever of tuberculization. I might say, in conclusion, that after a week's use of the quinine the parasites could no longer be found in the peripheral blood and the size of the spleen was markedly reduced. CASE III. WHOOPING COUGH, .ACUTE INFLAMMATORY RHEU.MATISM, LOBAR PNEUMONIA. The prexious hist(iry in this case is of some importance. The older brother of my patient is aged 25, is married, and lives in Newport, Ky. He RAXSOHOFF MEMORIAL VOLUME came to m_v office Februar}' \i, 1902, suffering from acute follicular tonsil- litis. He thought that there might be some di])htheria connected with his case, so. afraid of infecting his infant son, he determined to go to his moth- er's home in Cincinnati. He was well in a few days, but about a week after 1 first saw him, a younger Ijrother, aged 14. also living with the mother, was taken down with a similar trouble, and in another week the youngest brother, aged 8. On April 3 I was called to see the fourteen-year-old boy, Frank, and found him suffering from acute inflammatory rheumatism affect- ing the right ankle ; next day it had moved over to the left. Under combined salicylate and alkaline treatment he rai)idly convalesced without cardiac lesion or involvement of other joints. On April 6 I was asked to see H. ^., me eight-year-old child and the subject of the present report. He was suffering from a mild fever and rather a severe cough, not in any way spasmodic, while on physical exam- ination there was but a mild bronchitis present. On April 12 the fever rose rapidly and he complained of severe pain in the right ankle and shoulder. Examination showed the shoulder to be exceedingly painful and tender, though J could detect no swelling; the ankle, however, showed all the evi- dences ot an acute inflammation. The ne.xt day the other ankle was involved, the disease then transferring itself to the wrists and fingers. He also resiJonded to the combined treatment. ( )n .•\pril 14 the cough becaiue dis- tinctly paroxysmal, the child having about eighteen to twenty attacks in the twenty-four hours; the attacks occurred mostly at night and in the early morning hours, and ended in the typical whoop. I heard him in several of his paroxysms, and there could be no doubt as to the existence of whooping- cough. Belladonna was given and pushed to dilatation of the pupils, with the results so far as lessening the number and severity of the attacks was concerned. On April 30 another rise of temperature super\ened, soon fol- lowed by dullness and bronchial breathing in the lower right lung. The examination of the sputum revealed the diplococcus of Fraenkel. Crisis occurred on the fifth day of the disease, and convalescence from his triple infection proceeded rapidly, I have seen both of the younger children since their recovery on several occasions, and as yet there is not the slightest evidence of any cardiac involvement. This case has interested me because of the ajiparent casual relation exist- ing between the tonsillitis and the inflammatory rheumatism ; I have observed this relation often, though perhaps never in so satisfactory manner as in the present case. Osier, in speaking of the relations of pneumonia and rheu- matism, luakes the following statements: "The arthritis may precede the onset, and the pneumonia, possibly with endocarditis and pleurisy, may occur as a complication of the rheumatism. In other instances, at the height of an ordinary pneumonia, one or two joints may become red and sore. On the other hand, after the crisis has occurred pains ;uid swelling m;iy come on in the joints." Pai)c m MARK A. BROWN CASE IV. TYPHOID FEVER AND SINGLE TERTIAX MALARIA. The term typho-malarial fever has been in common use in medical litera- ture for many years, and even at present one occasionally encounters it. It was supposed in past years that there occurred a combination of the typhoid and malarial poisons — a community of interests or trusts, as it were — and that this new combine manifested itself in "ways that are dark and tricks that are vain," however, to the complete baffling of the common people, /. c, the physician. The latter, however, boldly came to the front and an- notmced with pride that the new combine manufactured a product that, when poured out into the '^vsicm, caused a continued fever with marked remissions which was extremely resistant to quinine. This was satisfactory to all concerned with the exception of the poor patients, who didn't count, as they always have to suffer in the cause of science, anyway, so they were deluged with quinine until their ears rang and rang again and they were deaf to their own entreaties. Laveran's discovery of the Plasmodium malaria? straightened matters considerably, and the introduction of the agglu- tination test of Pfeiffer-Widal completed the route of th. Typho-Malaria Trust. Chills, with the added phenomena of heightened fever and sweats, are not at all uncommon at any stage of typhoid fever. The disease may be ushered in with a chill, though this is rare. During the course of the disease chills may be the premonition of some such complication as pneumonia, pleurisy, otitis, periostitis or perforation ; or they may follow a too vigorous use of coal-tar derivatives, particular guaiacol locally applied to the abdo- men. During convalescence — and these are the cases to which the term typho-malaria is so often misapplied — they may occur bearing no relation to the above-mentioned causes, but from reasons not entirely understood, though probably dependent upon septic infection or autointoxication, as when the bowels have been allowed to remain confined for several days. Hov/ever, a coincident infection with the malarial parasite may occur at any time during the typhoid attack, though it is rare, and a positive diag- nosis must not be made without finding the Plasmodium in the blood. In most cases there has been a previous malarial attack, and the flare-up of the latter occurs during the typhoid convalescence. P. K., Jr., aged 24, a native of Cincinnati, and has lived in this neigh- borhood all his life. Was first seen on May 10, 1900. Previous history negative, aside from the ordinary diseases of childhood and an attack of chills and fever a year ago, which had promptly responded to quinine. ^^l^en I first saw him he had been sick about a week with the usual initial symptoms of typhoid fever, including the nose-bleed. In a few davs the spleen could be palpated and rose-spots developed upon the abdomen. The Widal reaction, made several times, was positive. The attack was quite a mild one and was unaccompanied by chills until convalescence was well established. Indeed, the attack was so light that it was not found necessary RAXSOHOFf MEMORIAL VOLUME to adopt any antipyretic measures, though the temperature did on several occasions exceed 103 degrees. (I have found that among people of ordinary inteUigence a fairly reliable temperature record can be kept, whicli can. if found necessary, be subsequently charted ; and I have made it a rule in fevers to appoint some reliable member of the family to take the tempera- ture regularly, as was fortunately done in this case.) When the evening temperature approached the normal, visits were made late in the afternoon, so that the evening temperature at least could be verified. (In the evening of May 28, convalescence having been well established, the temperature was found to be 101.8 degrees. The mother told me that the boy had had a slight chill at ten that morning, and that his temperature had gone to 103.8 degrees by noon. He had then broken out into a sweat, and by 3 :00 p. m. the fever had dropped to 102.6 degrees. The next morning the temperature was normal, and I obtained a fresh specimen of blood, which was found to contain an abundance of half-grown tertian malarial parasites. He had no chill that day. and the evening temperature was but 99.2 degrees. He was ordered ten grains of the bisulphate of quinine, to be given at eight the following morning. The chill occurred at about 10:15 a. m., the temperature going to 103.4 degrees by noon. Quinine bisulphate was then ordered in four-grain doses three times a day. with a resulting disappear- ance of the malaria. As said liefore, the typhoid had about run its course, so that the patient was soon able to be discharged. He has iiad one attack of malaria since that time. In this case there was a coincident typhoid and malaria infection. The diagnosis of typhoid was made by the history, the enlarged spleen, the char- acter of the fever, the rose spots and the W'idal reaction. The diagnosis of single tertian malaria was made by the occurrence of morning chills and rigors every third day. the finding of tyjiical tertian organisms in the blood and the therapeutic test. DISINFECTION OF THE KNEE JOINT.* ROBKRT P.. COFII-LD. M. D. Cincinnati. ^^'hether in civil or military practice, it is generally conceded that sejjtic infection of the knee joint is one of the most serious conditions that the surgeon can he called on to treat, endangering, as it does, both the future usefulness of the joint, and at times, the very life of the individual. In civil experience we have formerly been led to a profound distrust of the ability of this particular articulation to deal with infective processes. In septic arthritis, an arthrotoniy was usually advised and drainage tubes or wicks were inserted into the joint cavity, or through and through drainage was established and the tubes allowed to remain for at least a number of days. Besides producing an evil mechanical effect on the synovia and carti- lages, the drainage material provided an ideal reservoir for the pabulum in which the organisms could multiply and travel from within outward. si)read- ing infection to the para-articular structures, or from without inward, carry- ing secondary infection from the skin into the joint cavity. The anatomic structure of the knee joint is such that when it is severely infected over its whole extent, drainage becomes a serious and difficult matter, and even though skilfully done, it is a most unsatisfactory proced- ure, often resulting in the tracking of the infection along the muscular and fascial planes, above or below the joint, with the accompanying dangers of septicopyemia and severe damage to the joint structures, resulting in anky- losis. COXDITIOXS XECESS-ARV FOR F.AVOR.-XBLE RESULTS, The results achieved in the present war, in treating infected wounds of the knee by disinfection and immediate closure, have been the source of much surprise and satisfaction. Favorable results, however, with restora- tion of joint function, seem to depend on the observance of certain princi- ples which are doubtless of equal importance in treating septic arthritis of autogenous origin : 1. The operation must be done early, before the spread of infection and the disorganization of the joint structures have had time to occur. 2. Thorough lavage of the infected and contaminated areas, followed by primary closure of the joint capsule, is essential. 3. Foreign bodies must not be allowed to remain within the joint cavitv. 4. When drainage is used at all, it should be carried down to the cajisule, but not into the joint cavity. 5. Immobilization of the joint must be secured by adequate mechanical fixation. •Read before the Sectifm on Orthopedic .Suruery .it the Si.\tv-ninth .\nnua1 Session of the American Medical Association. ChicaKo, lune. 1918. From the lournal of the .American .Medical Association, October 19, 1918. RANSOHOFf MEMORIAL VOLUME In order for a surgeon to carry out these principles effectually, it is of the utmost importance that a diagnosis of suppurative arthritis be made early in the course of infection. This is not often difficult, since the joint involve- ment usually accompanies or follows a focal or general infection, originating elsewhere in the body, such as. gonorrhea, tonsillitis, otitis media, scarlet fever, pneumonia, etc. This form of arthritis may be secondary to a serous synovitis or it may start without any obvious serous stage. The septic joint is often ushered in with a chill, the temperature is elevated, the capsule becoines distended with fluid, and the joint is inflamed and jiainful and is held in a semiflexed posi- tion b\' the spasmodically contracted muscles. Every joint that shows evidence of inflammation and eft'usion. during the course of a focal or general infection or following it should be aspirated under strictly aseptic precautions for diagnostic purposes. The nature of the aspirated fluid will be a very definite guide as to the proper course to pursue. The bacteriologic side of the investigation so often fails to reveal the presence of micro-organisms in the joint fluid, either in smears or cultures, that considered by itself, it carries little weight, and negative findings in this regard should not influence the course of our treatment. The cytologic investigation of the joint fluid, however, is a distinct aid to the diagnosis, and at times will materially influence the prognosis, in joint eft'usions. A high percentage of polymorphonuclear leukocytes found in a sample of the aspirated fluid will afford positive evidence of a septic condi- tion. The normal synovial fluid from the knee joint is acellular. Pus. which consists of practically 100 per cent, polymorphonuclear leukocytes, is a surgically visible sign that infection of the part has occurred and calls for prompt surgical intervention. TF.CHXIC OF DISIXFF.CTIOX. The technic which 1 lia\e followed in disinfecting the knee joint is briefly as follows : The knee joint is prepared the day previous to operation by being shaved and scrubbed and wrapped in sterile dressings. After the patient is anesthe- tized, the field of operation is further sterilized with benzin and iodin. An incision l_^-2 or 2 inches long is made parallel to the inner or outer border of the ]5atella, extending into the joint cavity. If found desirable this incis- ion may be extended to facilitate a more complete ex])loration of the joint. By means of a gravity .syringe, placed high enough to give the stream con- siderable pressure, the joint cavity is now thoroughly flushed for fifteen or twenty minutes. Instead of using the sterile glass tip. commonly attached to the tubing leading from tlie container, it is better for the operator to use a soft rubber tip which may be inserted into the various recesses of the j(;int without the danger of injuring their delicate lining. \'arious solutions have been used with success for disinfection of septic joints. Some operators even assert that the results do not depend on the I'aof 12 ROBERT B. COFIELD nature of the solution employed, but rather that it is the thorough mechanical cleansing which is the important factor. However, since it has been shown that the synovia and cartilage withstand very well the active disinfecting agents, and since the pathotjcnic organisms are harbored within the synovia and para-articular iis-ut>. and not in the joint cavity, I prefer to use an active disinfectant which pu>sesses a penetrating as well as a cleansing action. Mercuric chlorid, 1 : 15,C00, in salt solution, as suggested by Dr. Cotton of Boston, maintained at a temperature of about 115 F. and this followed by physiologic sodium chlorid solution, has proved very satisfactory. Since the capacity of the synovial cavity of the knee joint reaches its maximum when the leg is flexed to an angle of about 25 degrees, and since the conients of some of the bursae communicating with the joint are most easily emptied when the limb is in a semi-flexed position, it is very impor- tant that flexion and extension of the juint should be jjassixflv carried out while the cavity is being flushed. 'I'his will aid materially in ridding the joint of the necrotic material and pus that have accumulated in these various pouches. It is also advisable repeatedly to press the edges of the wound close about the tip of the syringe in order that the fluid may tlistend the joint capsule and penetrate and flush out its various recesses. The objects sought by arthrotomy and irrigation of the joint ca\ity are: 1. Relief of the intra-articular tension, which d(iubtk-» has a deleterious effect on the svnovial membrane and cartilages Ibrougli its interference with the circulation and the normal secretory fiuiction of the synovia. 2. The removal of the necrotic material which acts as a culture medium within the joint cavity. The nature of this material i>recludes its removal by means of the trocar or an aspirating syringe. 3. The cleansing and disinfecting action on the synovia, which aids it materially in regaining a normal function and renewing its fight against infection. The synovial membrane, like other serous membranes, has an enormous capacity for combating infection if it is a fairly normal condition. After disinfection, the capsule is closed with catgut sutures, and if a drain is used at all, it is placed outside the synovial meiubrane for the sole purpose of taking care of the extracai^sular infection. The wound is closed in layers and the joint is thoroughly inimoliilized, preferablv bv a plaster-of-Paris spica including the foot. A fenestra may be cut over the knee and if an increase in the inflamma- tion and effusion should occur, aspiration may be repeated, depending on the nature of the fluid as to the future course of procedure. It is not frequent, however, that any further difficulty is encountered. The temperature and pain usually subside within a few days, and the joint gradually resumes a normal condition. POSTOPERATIVE -MEASURES. The limb is maintained in a position of physiologic rest until the wound is entirely healed and all signs of inflammation have disappeared. The RAXSOHOfF MEMORIAL VOLUME patient is then given the privilege of active motion once or twice a day, depending on the sense of pain as a guide to the extent of movement. Later, gentle passive motion, along with heat and massage, will often hasten recov- ery, but at first the utmost gentleness is necessary in order to minimize the risk of exciting a recrudescence. The absence of signs of inflammation does not always assure the absence of pathogenic organisms, and well meant efforts to establish mobility may set up an active condition within the joint, if passive motion is applied too vigorously or begun too soon. Should fibrous adhesions form, which we feel reasonably sure are peri- articular, they may be broken down by forced manipulations, with the patient under full anesthesia, in order to secure complete muscular relaxation, thus permitting the movements to be carried sufficiently far in all directions. Intra-articular adhesions are best treated by gradual correction by means of suitable mechanical appliance, since rough handling is followed by further damage to the joint structures and still greater limitation of movement within the articulation. THE MECHANISM OF SHOCK AND EXHAUSTION.* By Gkokc.e W. Crilk. M. D., F. A. C. S. Cleveland. The man in acute shock or exhaustion is able to see danger, but lacks the normal muscular power to escape from it ; his temperature may be sub- normal, but he lacks the normal power to create heat ; he understands words, but lacks the normal power of response. In other words, he is unable to transform potential into kinetic energy in the form of heat, motion, and mental action, despite the fact that his vital organs are anatomically intact. His mental power fades to unconsciousness ; his ability to create body heat is diminished until he approaches the state of the cold-blooded animal ; the weakness of the voluntary muscles finally approaches that of sleep or anes- thesia ; the blood-pressure falls to zero ; most of the organs and tissues of the body lose their function. It is evident, therefore, that in exhaustion the organism has lost its self- mastery. Self-mastery is achieved only by the normal action of tlie master tissue — the brain. In exhaustion, then, is the brain primarily exhausted; or has some other tissue or organ functionally broken down, and has that breakdown carried with it exhaustion of the brain? If the latter, then what organs and tissues are vitally necessary to the brain for the performance of its function? Obviously, the exhaustion of any organ or tissue not vital to the performance of brain function need not be considered, since it probably would not be a direct cause of acute exhaustion. I. TISSUES AND ORGANS WHICH BEAR NO IMMEDIATE RELATION TO THE PROBLEM OF ACUTE EXHAUSTION. Among the tissues and organs that are not immediately vital to the brain, within the period of death from acute exhaustion, are the bones and joints, the connective tissue, the neutral fats, the skin, the genito-urinary system, the digestive system, the gall-bladder and ducts, the lymphatic vessels and glands, the salivary glands, the spleen, the sweat glands, the pancreas, the thyroid, the thymus, the organs of common sensation, the nails, the hair. Want of activity of any of these organs or tissues individually or collec- tively cannot produce acute exhaustion in the sense in which that word is here used. That is to say, a man in exhaustion from the injury and the struggle of battle would not be restored if he were given rested eyes, rested ears, rested sweat glands, rested spleen, rested genito-urinary system, rested digestive system, rested bones and joints, rested connective tissue, rested skin, rested gall-bladder, rested fat. II. TISSUES AND ORG.^TCS WHOSE FAILURE OF FUNCTION MAY PRODUCE ACUTE EXHAUSTION. The tissues and organs, whose failure of function may cause acute exhaustion, are the respiratory system, the circulatory system, the blood, the muscles, the adrenals, the liver, and the brain. •From Journal A. M. A., November 23. 1920. Page 7.T RAXSOHOPf' .MEMORIAL VOLUME Respiuatory System. RELATION OF THE RESPIRATORY SYSTEM TO SHOCK AXD EXHAUSTION. The failure of the respiratory system to deliver sufficient oxygen to the Ijlood or to take sufficient CO, from the blood, exhausts and kills promptly. Failure of the respiratory system is not a universal, not even a common cause of exhaustion, for in the great majority of cases of exhaustion, the respiratory activity is even increased and there is no interference in the lungs with the exchange of gases. The interference with the pulmonary mechanism of air exchange that may cause exhaustion is most commonly produced by edema of the alveolar walls ; by pulmonary embolism ; by the exudations of pneumonia ; by fat embolism ; by the inhalation of water, or of pus, or of free blood; by excessive pleural effusion; by emphysema; by hemo- and pneumo-thorax. In each of these conditions, there is interfer- ence with the intake of oxygen and the elimination of carbon dioxid which may be suflicient to cause exhaustion and death. THEORIES REGARDING THE RELATION OF THE RESIMR ATORY SYSTEM TO SHOCK AND EXHAUSTION. Fat Eiiibolisin Theory. Roswell Park first suggested and Bissel demon- strated the presence of fat embolism in the lungs of ])atients who were diagnosed as being in surgical shock. Porter has extended Bissel's obser- vations into an inclusive theory of shock. He concludes that shock is due mainly to diffuse fatty embolism of the lungs. There are several facts that apparently are not harmonized by the fat embolism theory. (a) In cases of abdominal penetration, if there is no perforation of the hollow viscera and no hemorrhage, there is little shock; if there is either perforation or hemorrhage, or both, there is shock. Since, in either case, the same fat areas have been traversed, it follows that the traversing of the fat was not the determining factor. (b) In emotional shock, so common in battle, it is difficult to assign to fat emboli a causative role. (c) In shock from burns, the difficulty is no less. (d) In shock from chest and head injuries, i! is almost as difficult to as.sign a causative role to fat emboli. Many other examples may be cited. On the other hand, surgical literature contains many accounts of the presence of fat emboli in fracture cases — especially fractures of the long bones, and these cases show no shock at first, hut later develop a train of symptoms resembling shock. Wiggers performed a series of experiments to determine whether the mechanism which causes failure of the circulation after the intravenous injection of oil is the same as that which causes circulatory failure in surg- ical shock. He concluded that circulatory failure produced by fat emboli must be distinguished from circulatory failure due to surgical shock. The GEORGE W. CRILE conclusions of Wiggers are in more complete accord with surgical experi- ence than those of Porter. ^Vith respect to the CO, treatment which Porter proposes, on the theory that (he increased action of the diaphragm caused by the CH^ would force the fat emboli out of the capillaries into the free circulation, it would obviously be difficult to determine how nuicli nf (he clinical result might be due to pooling of the blood in the abrlominal \cins, for which Porter advises CO, inhalation, and how much to pulmonary fat embolism for which also he advises CO, inhalation. That is, would the clinical result be due to the pumping of the blood out of the abdominal ves- sels by the increased respiration induced by the inhalation of CO^, or to the driving of the fat out of the lungs, or would it be due to the relief of acapnia (Henderson) ? But since in practice the CO, treatment has yielded no advantage to the patient, this point will not l)e [Jursued further. Henderson's Acaj^nia Theory, ^'andell Henderson has plausibly advo- cated the view that excessive ventilation of the lungs — resulting in excessive elimination of CO, from the blood — is the cause of shock. Since the respira- tory center is controlled largely by the CO, tension of the blood, it follows that in shock the respiratory exchange would be diminished, so that, as Henderson believes, there would result a state which is below the jjoint of oxygen safety, Henderson's theory is one which every surgeon wf)uld hope might be true, for apparently it would make both the prevention and the cure of shock easy and simple. There are many arguments in favor of this theory. The disturbing efifect of excessive ventilation of the lungs is apparent. It is true that oxygen improves the condition of the patient in shock, that lack of oxygen leads to acidosis. Nevertheless there are certain difticulties in the way of accejJting fully Henderson's conclusions. (a) As we have stated above, the clinical use of CO, in shock has not proven to be of much value. It is possible that this is because .serious intra- cellular damage has been inflicted upon certain vital organs before the CO, treatment was begun. (b) In my laboratory, animals under curare and continuous ade(|uate and even artificial respiration — thus eliminating the excessive ventilation (acapnia) factor — could still be killed by shock from trauma. •(c) Protracted consciousness — insomnia — in animals, subjected lo no other excitement, causes complete exhaustion. Acapnia could scarcely be a factor here. It should l)e added that Henderson has not discussed this type of exhaustion. CONCLUSION. In exhaustion from running, from fevers, from trauma, from anesthesia, from excision of the liver, from excision of the adrenals, from hemorrhage, from emotion, from insomnia, the exhaustion is not in any way related to the lungs. If there is a coexistent defect in ihc pulmonary function, by so much the more readily is exhaustion produced by trauma; by emotion, by RANSOHOFF MFMORIAL VOLUME fever, by exertion, liy hemorrhage, etc. We. therefore, conclude that the Iirimary cause of exhaustion may be found in the pnUnoiiary system, but that this is not a coiiiiiioii primary cause. Circulatory System. I'aihn-e of the circulation exhausts and kills inevitably, and failure of the circulation is established sooner or later in acute cases of grave or fatal exhaustion. The question therefore is : Is the failure of the circulation a primary or a secondary cause of exhaustion, or is the circulatory factor sometimes a primary and sometimes a secondary cause of exhaustion? THK HE.\RT. The heart may be unable to pump the blood stream forcibly enough to maintain adequate circulation, in which case general exhaustion will occur as the result of lack of oxidation of the tissues. Exhaustion occurs clin- ically in the myocarditis of acute or prolonged infections; as the result of excessive muscular exertion; in anemia; in the presence of valvular defects, r.ut observations in both the clinic and the laboratory show that in surgical shock and exhaustion, the heart muscle has not failed. DISTRIBUTION OF BLOOD. Pooling in the larger veins. A number of observers have held the view I hat in shock the blood accumulates in various blood-vessels, this pooling becoming in effect an intravascular hemorrhage. There are certain facts, however, which arc not harmonized by this theory. (a) In the author's laboratory, experiments showed that shock could be produced in animals in which the abdominal vessels or the thoracic aorta had been excluded by ligation, though not quite as readily as in the controls. Erlanger and others have shown that excision of all the abdominal viscera does not lessen the liability to shock. In our experiments we found al.so that if the intestines were so tensely distended with water as to drive out all the blood, then trauma of the peritoneum no longer caused a primary fall in blood-pressure, but death from shock might occur. Many dissections before death, many autopsies after death from trauma to other parts of the body than the abdomen, showed that tlie blood was held in the veins everywhere, as in death from other causes. (b) As stated in a preceding paragraph. Porter has proposed the inha- lation of CO2 for the purpose of increasing activity of the diaphragm, to the end that the supposed accumulation of blood in the abdomen would thus be put into more active circulation. No clinical advantage from this treat- ment has been reported. (c) Treatment with intraperitoneal injections of pituitrin. as sug- gested by Cannon, even more effectively facilitates the splanchnic venous circulation than does Porter's CC\, inhal;itinn, but this method has not proved to be a cure for shock. GEORGE ]V. CHILE From the evidence in hand, we are not warranted in concluding either that blood does or that it does not pool. We only infer that even if it does pool, this is an end effect — not a primary cause of shock. Accumulation of the Blood in the Catyillaries. Cannon has advanced strong arguments in favor of the view tliat the small blood-vessels — the capillaries — are dilated, and in dilating have engulfed so much of the volume of the blood as to seriously interfere with the circulation. If this were true, then the universal bandaging of the body alone, or blood transfusion alone, or bandaging and blood transfusion combined, should both prevent and cure shock. But both laboratory and clinical experience show that. although these measures are useful, they are not specific. VASO-MOTOR MECH.AXISM. Is the vaso-motor mechanism a factor in shock? In 1897 the theory that shock was due to the impairment or breakdown of the vaso-motor mechan- ism was proposed by the writer. Owing to the fact that control of the blood-pressure did not specifically cure shock it soon became obvious that exhaustion and shock included much in addition to the failure of the vaso- motor mechanism. Opposing views as to the state of the vaso-motor mechanism have been presented by various investigators. (a) Seelig and Lyon have concluded that the vaso-motor mechanism is functionally intact in shock. (b) Porter has found that vaso-motor stimulation jiroduces a ])ro- gressively diminished rise in blood-pressure as shock deepens. This finding is in accord with our own data. Porter has interpreted the blood-pressure change on the basis of a percentile rise, and has concluded that the vaso- motor mechanism is not altered in shock. It is open to question, however, whether Porter has not proved the opposite of his conclusions, for if, in shock, adrenalin be given intravenously, or pressure on a paw be made, the percentile rise interpretation will be reversed. Applying Porter's percentile interpretation to the effect of adrenalin the percentile rise would be over 300 per cent., that is, according to Porter's reasoning, the vascular state is three times better than normal, but nevertheless, the dog is dying. The error in Porter's reasoning may be made more clear by a homely illustra- tion. If a goad be applied to a fresh horse, the resulting increase in speed may be stated as a percentile increase. When the horse is in extreme fatigue and an equal goad is applied, the percentile increase will probably be the same, but nevertheless the horse is exhausted. (c) Erlanger and his associates found that the vaso-motor mechanism is exhausted late in shock. They suggest that the primary fall in blood- pressure may be brought about by the effect of painful stimuli and hemor- rhage. (d) Pike and Coombs beliexc that damages to the brain-cells must be included as one of the conditions of traumatic shock. RAXSOHOFF MEMORIAL VOLUME (c) W'iggers observed a steady fall in xaso-niotor tone in llie early phases of shock. He concluded that the ])eri|iheral resistance \vas dimin- ished, indicating diminished vaso-motor tone. Our experimental data show that there is no practical distinction to be made between external stimulation of the vaso-niotor center as in injury and operation, and internal stimulation by vaso-motor stimulants, as strychnin. Each in sufficient amount produces exhaustion (shock), and each with logic might he used to treat the shock produced by the other, ^\'e conclude, therefore, that in traumatic shock the vaso-motor mechanism is function- ally impaired or exhausted. Experience in the clinic, however, seems to show that, whereas in shock the depression and fatigue of the vaso-motor centers were very important, there must also be other important effects. This was all the more probable because of the time required for recovery; the long after-effects; the inade- (|uacy of merely raising the blood-pressure; the weakness antl debility of the injured animal before a fall in blood-pressure had occurred ; the facts that infection, loss of sleep, hunger and thirst predisposed to exhaustion and that ether anesthesia predisposed to exhaustion. All these clinical obser- vations demanded renewed research. The work of Hodge on fatigue in bees and birds suggested such an investigation. To that end the studies of the brain cells, which have been summarized in former publications, were undertaken. These studies immediately gave us illuminating results. Our argument was that if the \aso-motor center was fatigued in shock and exhaustion, other parts of the brain were probably fatigued also. If the brain cells were fimctionally altered, one would expect them to be phys- ically altered, as Hodge had shown was the ca.se in his studies of fatigue in the bee. \\'e argued that in shock not only are the vaso-motor cells ex- hausted, but the cells of the brain that ])reside over voluntary muscular action and mental action are also altered ; in other words, that the brain as a whole is altered, and is altered independently of, as well as in consequence of, the low blood-pressure di>e to the exhaustion of the vaso-motor cen- ters ; that the higher centers may well be affected even more than the vaso- motor The vaso-motor niechanisni alone, the blood-pressure alone, is not suf- ficient to account for all the phenomena of shock ; and although some of the causes of exhaustion may be found in the resjjiratory system, and some in the circulatory system, we must look elsewhere for the explanation of the vast majority of ca.ses of shock and exhaustion. Are these due to some change in the blood? THE BLCXJn. Chemical Cliaiujcs in the Hlood. The blood is a vital fluid for all the tissues. If there is insuhicii iit bidod. or if ihc l)l()od is sullicienlly impure, exhaustion of e\ery organ and lissu.e will fulldw. The acute exhaustion caused by hemorrhage is cured in a normal animal by immediate replace- Pagc so GEORGE IV. CRJLE ment of the lost blood by an equal amount of good blood from another animal. If impure blood is the primary cause of exhaustion, and no other jirimary cause exists, then the removal of impure blood and the substitution of pure blood should bring relief from exhaustion in proportion to tlie amount of impure blood exchanged for pure blood. If exhaustion is due to some change in the blood, then if an acutely exhausted animal had its blood withdrawn as completely as possible and normal blood replaced, the same process being repeated several times so as to be certain that a sufticient amount of blood had been exchanged, demonstrable relief should follow. But experiments have shown that not many cases of exhaustion may thus be benefited or cured. Moreover, animals exhausted by insomnia show no change in the blood picture, as has been shown by our experiments. \\'e have found, also, that in patients in whom exhaustion has developed grad- ually, there may be no change in the blood. The common pathologic change in the blood in acute exhaustion is acido- sis. If this were the primary cause of exhaustion, then infusion of sodium bicarbonate should prevent and cure ; but both laboratory and clinical evi- dence shows that alkalies neither prevent nor cure shock. Cannon has found decreased reserve alkalinity in wounded soldiers in shock. He found this decrease was more marked in operation under ether than in ojierations under nitrous oxid; he believes that a diastolic blood- pressure of about 80 is a critical level at which acidosis rapidly develops. These phenomena are obviously secondary causes of exhaustion. Cannon, Dale and Bayliss have recently found that the pulpefaction of muscles causes a fall in blood-pressure when the nerve sup])ly of the injured part in blocked ; and that this is prevented when the circulation of the part is blocked. Even so. macerated muscle products could be but a minor factor in the production of shock, for (a) tourniquets minimize shock only as far as they minimize hemorrhage; (b) spinal and local anesthesia almost specifically prevent shock; (c) many causes of shock, such as abdominal operations, joint injuries, skin injuries, etc., have no relation to muscle poison; (d) nitrous oxid anesthesia is all but a preventive of shock. How can these facts be reconciled with the view that the cause of shock is low blood-pressure, the low blood-pressure in turn being caused by muscle poi- sons? Even if under exceptional circumstances the presence of muscle toxins constituted a causative factor, their shock-producing value would be identical with that of toxemia from any other cause. Concentration of the Blood. The blood \oIume is apparently dimin- ished in shock. Has the plasma left the vessels and gone into the tissues? If so, is the process an adaptation or is it a pathologic effect? This point was investigated in our laboratory Ijy Drs. F. W. Hitchings, A. N. Eisen- brey, and C. H. Lenhart, who found that in shock the concentration of the blood was increased up to 20 per cent., but other considerations made it obvious that this is not a primary cause of shock. RAXSOHOFF MEMORIAL VOLUME "In the blood of the 'shock dogs' there was an increase in the nnniber of the red cells per cubic millimetre while in the blood of the 'hemorrhage dogs' there was a decrease in the nnmber of red cells per cubic millimetre. "In the 'shock dogs' there was a decrease in the number of white cor- l)uscles while in the 'hemorrhage dogs' there was a preliminary decrease followed by a marked increase."* Mann performed a more extensive research along the same line, and attributed greater importance to the increased concentration. Cannon has shown further evidence of loss of plasma in shock, and supports Mann's estimation of the value of this data rather than our own. Now, if increased concentration were the cause of the small amount of blood, if circulatory failure were due to a 'plasma hemorrhage' into the tissues, then adequate transfusion of blood should prevent and cure shock, but adequate transfu- sion of blood is not a specific cure. In addition, on this theory, the careful work of Hogan and Bayliss on the infusion of colloidal solutions, should have given us a cure, because it is known that these solutions do not leave the blood stream. But colloidal solutions fail to hold the blood-pressure — fail to cure advanced cases. The transference of plasma is probably an adaptive protection. Then, again, even granting that the blood contains impurities which cause exhaustion, where did the blood get those impurities? From the cells. And the cells? From their increased metabolism, ^^'hat caused that in- creased metabolism? Certain of the excitants of exhaustion. We conclude, therefore, that in the absence of primary disease — causing changes in the blood, and in the absence of hemorrhage, changes in the blood or in the blood-pressure are a secondary, not a primary cause of exhau.stion. VOLUXT.XRY .MUSCLES. If the voluntary system were exhausted primarily in shock, then there would be prostration, low temperature, lowered blood-pressure, but not the extremely low blood-pressure often seen in shock, no sweating, no loss of mental symptoms. Therefore, it at once becomes apparent that primary exhaustion of the voluntary muscles could not be adequate cause of all symptoms of exhaustion. Is exhaustion of the voluntary muscles the cause of the lowered body temperature? Is the inability of the muscles to act due to a primary change in the muscles, while the brain is normal? This seems improbable, for the following reasons ; (a) The voluntary muscle is more resistant — more than fifty times as resistant — to low blood-pressure and anemia as the brain. (Crile-Dolley.) (b) The muscles in the acutely exhausted subject show no histological GEORGE W. CRILE change. The)- can be made to contract by electric stimulation of their nerve supply, or by electric stimulation of the muscle directly. (c) It i.s a physiologic axiom that voluntary nuiscles are not as readily exhausted as are the nerve centers that govern them. (d) If there is primary exhaustion of the muscles, then, according to Bayliss, it would probably be due to the over-production of acid or other injuring by-products as a result of injury or of work performed. But in exhaustion from trauma under anesthesia, the muscles have done no work ; in exhaustion from fear, the muscles have done little work ; in exhaustion from overwhelming toxemia, there has been no muscular work. Finally, we know that in a \ast number of the injuries which cause shock, no muscle is involved, c. g.. injury of the skin, brain, knee-joint, hands or feet may result in .shock. We must, therefore, conclude that the voluniarv nuiscular system plays a secondary, not a primary role in exhausticm. We ha\c seen that the respiratory and the circulatory systems and the \oluntary muscular system are sometimes primary causes of exhaustion, and frequently secondary causes. We have seen that in exhaustion all these tissues sut+'er a variable amount of disability, but the primary common cause of shock remains to be disclosed. THE .\nRE.\.\LS. The criteria for the objective study of the adrenals are the adrenalin output, the electric conductivity, and the histologic picture. Elliott. Cannon. and others have found an increased adrenalin output and a diminished adre- nalin content in certain cases of exhaustion, c. g.. in exhaustion due to inhalation anesthesia, to infections, and to emotion. Short found no notable diminution in the adrenalin content in shock; Bedford found no diminution of adrenalin output in shock ; Mann disassociates the adrenals from shock. In our laboratory we found cytologic changes in the adrenals in exhaustion from any cause, including insomnia, these changes being more marked in the cortex than in the medulla. THE RELATION OF THE ADREN.ALS TO THE LUER .\XD TO THE RRAIX IX EXHAUSTIOX. Apparently adrenalin alone can cause the brain to greatly increase its work. By cross-circulation experiments, we have found that adrenalin causes increased activity of the central vaso-motor mechanism. Not only can adre- nalin, as Cannon has shown, cause all the basic phenomena of exertion, emotion, infection, etc., but it also causes brain-cell lesions identical with those produced by exertion, emotion, infection, etc., including the entire cycle of hyperchromatism, chromatolysis, swelling and even disintegration of the brain cells. 'Plie injecti(jn of adrcn.-ilin causes an immediate increase in the conductivity lus 20 OBECTOMY. Alu>ut 4 U'eek.^ After Operation Mrss McDonald: Pulse B. M. R. Pulse W. M. R. 104 ])lus43 EFFI'TT OF LIGATION- OF RIGHT SUPERIOR TIlYR(-)li:) ARTI'RY. Before Operation. About 4 Weeks After Operation Mrs. p.: Pulse B. M. R. Pulse P.. M. R. 130 plus 76 124 i)1us60 SI'.I.ECTIC)X OI" HEMOSTATS TO DETERMIXE XECESSITV OF LIG ATIOX IX THYROIDECTOMY. Many operators "tie off" all of their heiiiostats while others "tie off" only a very few, "taking a chance" with must of ilieni, or even go so far as leav- ing many of them in situ."' By the first method we consume a great deal of unnecessary catgut into the wound, thereby inviting infection and causing a greater reaction in the tissues. By the second method we endanger the patient with secondary hemorrhage or hematomata. For the past two years we have been using two different types of hemo- stats in all goiter operations. The types to be used are optional with the individual operator. We use the small Kelly forceps and the large Kocher. \Vhene\er we clamp fascia, or other structures, as muscles, etc., or small oozing points in fat, which we know will not bleed after the clamp is removed, we use the smaller forceps; whenever we clamp an artery or a large vein, or in clamping through the thyroid gland, or in clamping any structure which we know will require tying after the completion of the operation, we use a large Kocher forceps. It might seem that this would involve a great deal of thought and loss of time ; but we have found that we unconsciously pick up the proper hemo- stat and, if a nurse is passing instruments, that with only slight training she will hand the proper forceps. In using this method we ha\e found that we save time in knowing which hemostat requires ligature, we prevent the possibility of secondary hemor- rhage, and we also prevent the possibility of hemotomata following opera- tion. Leaving the clamps following lobe removal as suggested by Bartlett' becomes at once impractical because we save an enormous amount of time in knowing which clamps require ligature. JOSEPH L. DcCOURSY CONCLUSIONS. (1) Removal of both lobes and isthmus lias eliminated in large measure the necessity of preliminary ligation. (2) Removal of focal infections in itself is not sullicicntly effective in l)roducing a complete cure in thyrotoxicosis. (3) Basal metabolic rate determination and other tests have ])ro\en themselves as definite aids to diagnosis and treatment. (4) Greater risk can be taken in operating under local than with gen- eral narcosis. 1. Sandiford, Hndociinolosy. \'ol. IV, January-March, 2. BilHnes, Discussion of Focal Infections hy Fontaii June 12, 1920. 3. Bartlttt. ".\n Kmereoncy Ti-i hnic for Throideclonv July 17, 1920. SOURCES OF WASSERMAXX ERROR AXD THEIR CONTROL.* By Albert Faller. M. D. Cincinnati. That a biological test be of greatest practical utility it is necessary that it be as free from error as possible ; but since all such tests are more or less subject to error, it becomes essential that all such possible sources be kiiozvii, that provision may be made for their recognition and proper interpreta- tion, and when such errors are inherent and cannot be remedied, it becomes necessary to adopt a substitute test or a modification, which is free from such error. There is, perhaps, no biological test which has a greater field of useful application in medicine than the W'assermann complement fixation test for syphilis, which has become almost indispensable in every field of medical endeavor. It is to be regretted, however, that such a test shduld at times have its usefulness nullified, that it should at times be misleading, that its performance should occasionally lead us into greater and more harmful error than though it had not been performed. Such, however, is the status of the Wassermann test as it is commonly applied to-day ; that these sources fif error and their control may be sufficiently accentuated is the apology for this paper. The causes of \\'assermann error, inherent in the test itself, are: 1. Presence of but few antibodies, this resulting from (a) healing of serum; (b) effect of treatment; (c) early stage or .so-called latency of disease. 2. Presence of natural anti-sheep amboceptor in quantities sufficient to disturb the proper ratio of ^^'assermann factors. Noguchi has shown that during the first five minutes of heating about 40 per cent, of antibodies (reagines) are destroyed; during the next five min- utes 20 per cent, disappear, and at the end of inactivation but 25 per cent, remain. Thus the necessity for eonseri'ing antibodies, especially in inten- sively treated and in early and latent cases, becomes apparent, and as these form a great part of the cases coming to us for diagnosis, it is equally appar- ent that a large percentage of these cases do not readily lend themselves to the unmodified ^\'asse^mann technique. These findings have led the writer to include an active control in every W'assermann, and he has refieatedly seen a barely perceptible inhibition result in a two plus positive reading. It can readily been seen how a negative report might have been rendered in these cases had the straight W'asserman technique alone been em])loyed. This is one great group of cases wherein the W'asserman causes us to give our i^atients tacit permission to de\elop labe>, paresis and visceral lues in later life. iber 14, 1914. Read before the Academy of Medicii ALBERT FALLER The second great source of error is the presence of natural anti-sheep amboceptor in sufficient quantity to destroy the proper ratio of Wassermann factors. Excess of amboceptor is disconcerting only when antibodies are few. It is the writer's experience that blood containing enough natural anti-sheep amboceptor and antibodies to cause a four plus reaction, shows no hemo- lysis when considerable amboceptor is added, but frequently does show effect in one plus cases ; it is loss of balance between amboceptor in excess, and antibodies deficient in amount, that causes negative reactions where posi- tives one should oljtain ; the smaller the amount of antibodies the more probable that excess of amboceptor will destroy a delicate balance ; where antibodies exist in great number a comparatively rough approximation of reagent quantities may be tolerated, but in the presence of small amounts a most delicate manipulation is imperative. Most human blood contains enough anti-sheep amboceptor to hemolyze sheep's corpuscles in considerable quantities. The writer has frequently found specimens capable of causing hemolysis in proportion of one-tenth cc. of serum to 1.4 of sheep's corpuscles. Bauer has based his modification upon the natural hemolytic powers of human serum. The complement of human serum, while usually not in great amount, is, nevertheless, quite con- stantly present, and increases the effect of the amboceptor. The Wasser- maiui technique, while demanding careful titration of amboceptor added to the test, takes no cognizance of the amount of this factor naturally present in the serum ; it does not seem reasonable that a serum containing a great amount of amboceptor should have added to it the same amount of this ingredient demanded by a serum containing little or none of this body. It is obvious that each serum to be examined should be titrated as carefully as any other ingredient of the test ; each serum should be individuali::ed; it should be carefully titrated for its amboceptor and complement content ; the presence of anti-complementary substances should be sought and a com- parative estimation of antibodies should be made. To correct the above errors, several modifications of the Wassermann test have been proposed ; all possess merit and most possess as great possi- bilities for error as does the parent test. Bauer, recognizing the fact that most sera contain enough amboceptor for all hemolytic purposes, performs his test exactly as does Wassermann. except that he adds no amboceptor. This would obviate one great source of error, but Bauer, like Wassermann, inactivates, and, therefore, destroys reagines, and border line cases may easily be overlooked by this method ; then, too, some sera contain insufficient amounts of amboceptor, and in such cases this method would not be applicable. Margarita Stern ignores amboceptor and utilizes the natural comple- ment ; she therefore does not inactivate, thereby preserving all antibodies. But complement is the most inconstant and labile feature of serum and it is Pape HI RANSOI/OFI' MEMORIAL I'ULUME usually necessary to add complement from other sources ; then, too, there is here danger of excess of amboceptor, as the amount in the serum is not utilized. The writer considers the method of Bauer a very useful modification, hut finds the method of Stern of very Ihuitcd utility. Those methods requir- ing anti-human amboceptor will not be discussed here, as the writer has had but very limited experience with them. Of all complement fi.xation tests, the writer considers the so-called Hecht-Weinberg test the most ti'idely applicable and useful ; this method is useful, not only as a complement fixation test, but because of the amount of knowledge it yields concerning the pecularities of each serum ; it indi- cates antibodies; it shows the presence of anti-complementary substance and the amount of amboceptor and complement present; armed with this knowl- edge, the serologist is in position to properly interpret the significance of the variutts tests and to select the one best suited to the serum to be tested. The Hecht-Weinberg test makes use of the natural anti-sheep ambo- ceptor and natural complement, and is performed with nnheatcd serum; it is therefore designed to overcome the great sources of error of the other tests mentioned; as performed by the writer, it also indicates the amounts of amboceptor and complement present. ( Parenthetically, the writer would say he considers the amount of natural amboceptor of great prognostic import, as he hopes to show in a paper in preparation.) The technique, as worked out by R. B. H. Gradwohl, of St. Louis, is as follows: Fourteen tubes are placed in a rack; into each is ]:)laced .1 cc. of serum to be examined ; then into the first ten tubes is i)laced descending amounts of salt solution, in the first tube .9 cc. descendinij to .1 cc. Then in these ten tubes is jilaced ascending amount of shee])'s corpuscles, begin- ning with .1 cc, and ending with .1 cc. This gives each of the first ten tubes equal volume ; these ten tubes are for the purpose of obtaining the hemolytic index — the hemolizing power of the serum. In the next three tubes is placed graded amounts of antigen, .2 cc, .15 cc. and .1 cc. The last tube contains only serum and is the control tube; these four are then brought to equal volume with salt solution. The rack is then placed in the water bath for one-half hour and shaken frequently. That tube which shows complete hemolysis of the greatest amount of sheep's corpuscles is then noted, and gives the hemolytic index. Blood corpuscles are then added to the last four tubes according to this index: if this is from one to four, we add .1 cc. of corpuscles; if from five to seven, .15 cc, and if eight or more we add .2 cc. The rack is again placed in the water bath and results read as in the \\'assermann, when the control tube shows complete hemolysis. It is the universal ex])erience that a once negative W assermann may frcqiieiilly bccduic pusiiivc; a proof that infection, howcxi-r sm;ill in amount, slill existed; il is the writer's experience (and that of 1\. B. II. (iradwohl. AL BilRT PALLIIR who has had an enormous experience with this test) that when the blood becomes negative to the Heclit-Weinberg. it usually remains so. This, in connection with the fact that the Hecht-Weinberg is positive in the early primary stages of lues and in well treated and latent cases, indicates that the smallest amount of systemic infectioti causes reaction to this test. To illustrate the absolute necessity for Wassermann modification and for obtaining the hemolytic index, the following cases may be cited: Case of S. L. Hemolytic index 10, amboceptor content 14, Wassermann tests with heated and unheated serum are negative ; the Bauer and liecht- Weinberg tests are two i)lus positive. This is no doubt a negative W'asser- mann in a positive case of lues due to excess of amboceptor. This case one month ago, with an index of 6 gave a slightly positive Wassermann. Infec- tion in this case occurred twenty years ago. Case of R. L. : Has a chancre of se\-en days' duratiun ; no other lesion apparent: hemolytic index is 10, amljoceptor content is 14; Wassermann, heated and unheated, as well as the ]5auer test, are negative; the Hecht- Weinberg is one plus ]K>sitivc. Here the straight Wassermann is negative because of the destruction of the few anti-bodies i^resent and also because of the large amboceptor content ; this content also interferes with the active Wassermann ; the leaner test is negative because of inactivation ; the Hecht- Weinberg, utilizing a natural amljoceptor, and preserx'ing all antibodies, is slightly positive. Case of J. C, a hospital case, was admitted because of suspected diph- theria; has a necrotic tonsil; hemolytic index is 10; amboceptor content is 15; all tests are four plus positive, excess of amboceptor and heating of serum not influencing results in the presence of excessive amounts of anti- bodies. Case of W. T. : Has no index, both amboceptor and complement being entirely absent ; gives a slightly positive reaction with the unheated \\ asser- mann ; negative to the regular ^^'assermann. Having no amboceptor or com- jilement, this serum was not suited to the Hecht-Weinberg test ; having no amboceptor and but few antibodies, it was not suited to the Bauer test : hav- ing no complement, it was not suited to the Stern test, and having but few antibodies, it could not be heated for the regular Wassermann. Any test, other than the unheated Wassermann, would have resulted in error. This is a well treated case of paresis, where the original Wassermann gave a four plus positive reading. This case is now negative to unheated Wassermann. Such cases as these indicate that there is no one best method of testing all specimens of serum, and the writer wishes to especially emphasize this fact. If amboceptor is present in great amount, with enough antibodies to tolerate in activation, the Bauer test is acceptalile; if amboceptor and com- plement are present in sufficient (|uanlity, and no anti-comi)lementary sub- stances arc ])resent, then the Hecht-Weinberg, be the antibodies many or few: with low amboceptor and low complement content and few antibodies RANSOHOFF MEMORIAL VOLUME assumed, and no anti-complementary substances, the unlieated Wassermann ; in all cases of anti-complementary substances, the regular Wassermann must be relied upon. In conclusion, the writer would say that, in trying to simplify Wasser- mann and allied reactions, one is led far afield into the domain of ferment possibilities, and if we would make this field free from error, we must increase, rather than decrease, its complexities. The ideal condition for complement fixation work is first to become thoroughly familiar with the serum to be tested ; titrate it as thoroughly as any other integer of the test ; see where its error would most likely occur; and assign the chief signifi- cance to that test which you consider the ideal one for that serum. PRIMITIVE SURGERY OF THE WESTERN HEMISPHERE.* Leonard Freeman. M. D. Denver. I have selected this subject for my address, because it seems peculiarly appropriate to bring before the Western Surgical Association something about the prehistoric surgery of the West, which, as far as I am aware, has not been done before. Two causes of surgical and medical ailments were universally recognized among the early inhabitants of the Americas, one natural and the other super- natural. If the cause was not easily perceived, as was often the case, it was regarded as supernatural. The supernatural diseases were supposed to orig- inate in various ways: by the casting of spells, by contact with some objec- tionable person or thing, or by the presence of something in the system, such as an evil spirit, a stone, a piece of wood, a worm or an insect. Manifestly, they came just as near to the recognition of bacteria as they could without knowing anything about them. It must not be thought, however, that real causes were not given their due significance, if they made themselves sufficiently apparent, as often hap- pened in surgical lesions at least. The ancient members of our profession were by no means always as childish as they are sometimes represented to be. It goes without saying that supernatural ailments can be treated by super- natural means only, which accounts for the existence of the so-called medi- cine-man, with his impressive fetishes, antics and incantations. In this con- nection it should be understood that the word "medicine" was not confined originally to material remedies, but had in addition a magical and super- natural significance. Hence a "medicine-man" was not only a physician in our sense of the word, but was also a sort of priest, prophet, magician and all-around dealer in the mysterious. THE MEDICINE-MAN. The medicine-man^ was usually a person of more than ordinary tact, knowledge and intellect. In addition to being a surgical and medical author- itv, he also was consulted on many things concerning the spiritual and tem- poral welfare of his people. Although dealing extensively in the occult, he had a dignified and firm belief in himself and his methods, and was much in •Presidential addr ess deliv. :red before the Western Surgical Association, Omaha, Dec. 14, 1917. From The Jou rnal of the Amer ican Medical Associa ition, Feb. 16, 1918. 1. Althoi ..gh the title is I nasculine, it is inte resting to note that there were also "medicine- women," who held high places i, n the profession and no doubt deserved the confidenc re placed in them by their clien tele. The costu me and make-up of ; a typical medicine ■man is well described by M'Clcnachan: "The face is painted, usuall'y red, « ath yellow trimmings i about the eyes and mouth. The hair, alwa long, h. IS a tuft of feathers braided in at the crown; and to braids of hair hanging about the shoulders ar e attached horsehaii -5, snake r attles, she lis, etc.; o' vfer all is dusted red and yellov 1 paint. The ea rs are pierced by n ngs, and suspended from them hang shells, reaching tn the shouldei -s. .Uout the neck are strings of brighl : colored b< eads, with bird's claws, pebbles, buffalo teeth, etc :. The wearing apparel consist! i of a shii ■t made of rawhide, leggins. breech clout, moccasins .. and ovs ■r all a blanket or buffalo robe. The shir t is daubed with paint, with some hideous i 1 the bre: .St. The leggins are made to fit closely. but with a wide strip along the outside, to which i! ; attached beads, bones, etc. ' The blanket ; or robe. in either ca se gaily adorned. is loosely thro wn over the shou ilders." Of the mcc licine-man's methods nt. Hrdlicka sue- RAXSOUOFF MFM0RL4L J -GLUME earnest in spite of the legerdemain and grotesque dress and actions that he employed to emphasize his doings and impress their importance on the observer. There is even reason to believe that his fantastic dances and ges- tures, facial contortions and weird chantings exercised a hypnotic influence on his patients, leading to relaxation and sleep, which may have facilitated the recovery of some who would have been given up to die by more civilized practitioners. In fact, w^hen one comes to think of it, such things are merelv an exaggeration of that "personal influence" which every physician is sup- posed to exercise in greater or less amount. To a certain extent, the medicine-man was the ])rotector of the perse- Fig. 1. Head of Peruvian mummy, showmg trephine opening in left temporal region, and an apparent right facial paralysis ( U. S. Ethnological Reports). cuted. and the refuge of the fugitive. Even an enemy could find sanctuary in a medicine-lodge, where his wounds were dressed and his other needs attended to. We should indeed be proud that this same spirit has always characterized the medical profession at all times, and that it still exists among us. Looked at from this point of view, the Red Cross is a great medicine-lodge. It was not much easier to become a "nu-dicinc-man" in those (lavs than allv ct;. ' ! 11'? or kneariinp ( s-ii.- i u . - j.n. \ i. i, i .>,il:Ii employed more commonly ,r siipl" ' ' "—'■'"''•■ 1'.,,,^,! ini.li^uu iia>. U.l ,-kii.. ^ /.'.i .lUion of the objective cause of e di-. . ; ! . nlo the patient, passes wiili tiiicers moistened with saliva, remnii ^ l lintinR of the body of the patient as well as that of the ediciiK iiMises (made with voice, rattle or drum), commands and ihort.di ' t i : t-, i-Miiances given the patient, various symbolic representatives, irification nl llie tjiulv liv swt-rit t>atlis. purging and emesis, strong sucking, cauterizing, sacrifying, ceding, e-xternal applications, the administration, externally or internally, of secret magic or other edicine, and various regulations of the behavior of the patient. In the larger curat" veral medicinemen acted conjointly, or, if but one present, he may have from LEONARD FREEMAN it is now. The usual method was to spend at least a year with a preceptor, paying him well for his instruction. There was much to be learned and remembered, for these preceptors all varied in their bewildering practices, and it was customary to study under more than one. As with the modern doctor, even after graduation the life of the medicine-man was not one of pampered ease. He was compelled to resjjond to every call, night or day: although the Pueblos permitted an exception to the rule, if the unwilling physician could catch the messenger within a given distance and kick him. How many of us wish we had the same privilege. \l the patient died, the doctor also ran the risk of death, at the hands of the relatives ; and, at the very least, a number of failures to cure led to a loss of reputation and final dismissal from the profession. There was, how- ever, a saving clause, at least among the Pueblos, for when the medicine- man's power began to wane he could rejuvenate it by rubbing his b;ick Fig. 2. Scjuare trepliinc opening ( U. .'^. Etlinolngical Reports against a certain sacred stone. The location of one of these stones is still known. The fees were of good size and paid promptly, often in advance. They consisted, not luilike those of a country doctor, of such things as blankets, horses, skins, weapons and various other personal effects. It should be emphasized, however, that to the credit of the profession much charity work was done then, just as it is now. Curiously enough, there exists throughout the world a marked similaritv in prnnitive medicine which suggests, perhaps, a common origin of the vari- ous races. In accordance with this, the metliods of treatment were often identical among the prehistoric peoples of North, South, and Central Amer- ica, including the Indians, the Pueblos, the Aztecs and the Incas. The old Spaniards were in a position to observe these things and should have been able to tell us much about them; but unfortunately those aggressive pioneers were more interested in killing than in curing, so that their descriptions ^re RANSOHOFF MEMORIAL VOLUME unsatisfactory and meager. Enough has been handed down, however, to make it clear that considerable crude but efficient surgery was practiced, some of it being done in hospitals, at least in Mexico. PRIMITIVE AMERICAN SURGERY. Let us consider this primitive American surgery more in detail : Fig. 3. Large antemortem trephine opening ( U. S. Ethnological Reports). Trephining.- — As is well known, this is one of the very oldest surgical operations, and was extensively practiced by prehistoric peoples everywhere. It is probable that it was done not only for therapeutic purposes, but for other reasons as well ; for instance, to let out evil spirits, to obtain amulets for decorative and other uses, or merely as a religious rite. The wearing of amulets made from sections of skulls was a common custom among the earlier inhabitants of the world. They were mostly obtained postmortem, but some were evidently removed froin living captives, possibly with the idea that they were more potent as talismans against disease, or that they conferred on the wearer the physical or mental powers of the original owner.' But there can be no question that much trephining was also done for thera- peutic purposes — for fracture, epilepsy, insanity, convulsions, headaches, etc.— as it is among various primitive races to-day. According to archeologists, trephining was done far more frequently in Peru and Bolivia than in any other parts of the Western Hemisphere. Among 12,000 skulls from Bolivia, for example, 5 per cent, had undergone this operation, and in Peru the percentage was not much less, showing that the procedure was much more common then than now. Less is known about trephining in the United States, although occasional skulls with the charac- LEONARD FREEMAN teristic openings have been found in the tumuli of the mound builders. It was more frequent, however, in Mexico and Central America. Although many of the operations were done postmortem, others were antemortem, as is shown by the growth of bone around the edges of the openings. It may be inferred that some of the patients died during the operation, the button having been outlined but not removed. We can well imagine that a "death on the table" must have been accompanied with the .same bitter regret and disappointment as it is now. Fig. 4. Ahiltiple antemortem trephine openinf;s (U. S. Ethnological Reports) We are justified in believing that these surgical interventions were fre- quently for therapeutic purposes, because fractures are often found in con- nection with them ; and even when no fracture can be seen, it is not unrea- sonable to suppose that a puncture of the skull, such as must have been frequent from the spiked war clubs then in use, may have existed and been removed by the operation. And, in addition, the fact that the openings were sometimes at a distance from the break in the bone might well mean that the principle of decompression was recognized-^perhaps learned from experi- ence in trephining for headaches, epilepsy, insanity, etc. In fact, if we do not regard these operations as deliberate decompressions, they would seem to be purposeless. In the Smithsonian collection is the skull of a Peruvian muiumy on which the dried soft parts are still in place. A trephining has been done at the seat of a fracture in the left temporal region, the interesting point being that the face is strongly drawn to one side, apparently the result of paral- ysis — a most uncanny phenomenon, to say the least (Fig. 1). Most of the trephining operations in America do not seem to have been done very skilfully. They were crude jobs with crude tools that often slipped during the laborious process, as shown by scratches on the adjacent parts of the skull. The shape of the opening was usually square or oblong, although some- times round or oval. The square opening (Fig. 2) was peculiar to South RANSOIIOFf MEMORIAL J-QLl'MF. America. It was made by cutting four rectangular intersecting grooves, almost but not quite through the bone, and then prying out the loosened piece of skull. The round openings (Figs. 3 and 4) were produced by gradual scraping, as shown by the characteristic of uncompleted operations. From the nature of the grooves and the lines on their sides, it is jDrob- able that they were cut with a stone instrument, like a spear head, set in a handle and possessing a rough and rather blunt point — a kind of single- toothed, stone saw, as it were, by means of which the bone was slowly worn away by a to-and-fro motion aided by strong pressure. It is likely that the round holes were scraped out with sharp flakes of flint or obsidian, as is still done by certain more or less uncivilized tribes in various countries. For a number of reasons, it is supposed that the patient's head was held between the knees of the operator, who laid open the scalp with a crucial incision and then sawed, scraped and pried away at the unfortunate vie- / : 1 m J ■ Fig. Splint made of sticks held together by strips of rawhide (Medical and Snrgical Reporter. 1879, 2). tim's calvarium. with many slips of his crude instrument, until an opening was made. The time required, as established by experiment, must have been at least an hour and often much longer. It may have been that some sort of anesthetic was employed, such as was used by the Pueblo Indians ; but if not. what a nightmare of an experi- ence it must have been for the patient, to say nothing of the nervous strain on the surgeon ; although, when one considers the matter calmly, it could not have been much worse than the torture occasionally inflicted on us by our dentists. After all, much depends on the point of view. It should be mentioned that trephining is still practiced in the same primi- tive manner by native medicine-men in the mountains of Peru, although they now employ pocket knives, chisels, etc., instead of instruments of stone. The LFAINARD FREEMAN operation is generally done for fracture, and is surrounded by great secrecy and certain mystic rites. It is said to be quite successful. Fractures. — In the treatment of broken bones, the results were often surprisingly good. It was cuslomary to set them, more or less skilfully, by pulling and manipulation ; bul permanent extension was not often, if ever, employed. Splints of \ariims kinds were in universal use. They frequently were made of bark, tin- natural curves of which facilitated adjustment to the limb, especially after soaking in hot water and cutting away portions to accommodate bony prominences about the joints, (irass, scrapings from tanned hides, and other soft substances were used for padding. ( )cca>ion- ally the splint was filled with moist clay, which enclosed the limb somewhat splints found in anc the Stale Histc n clift dwellings of southwestern Coloi cal and Natural Histor\ Society, Denv like a plaster cast, and must have been both comfortable and effective. A window was aKvays left o\er the site of a compound fracture to permit of attention to the wound. Other sorts of splints were made from sticks or ])liablc branches, such as green willows, held together by strips of bark or leather (Fig. 5). The Cliff Dwellers of the Southwest, who from their mode of life must have broken their bones often, knew how to manufacture splints that scarcely could be improved on. Specimens exhibited in the Museum of the State Historical and Natural History Society, Denver, are beautifully made from polished wood and correctly curved to fit the limbs for which they were intended, the edges being nicely rounded to prevent injury to the skin (Fig. 6). Similar splints were employed by the Aztecs. Often the splints were removed and the limb massaged, a practice that gives good results and deserves more attention than is given to it by modern surgeons. In the treatiuent of fractures, the Hopi Indians employ s])linters of trees which have been struck by lightning ; not, however, as splints, but merely as fetishes. For some reason or other, they believe that those who have them- selves received a lightning stroke are possessed of special skill in the care of broken bones — rather a severe requirement for a sjiecialist in fractures, one would think. RANSOM OFF MEMORIAL VOLUME In the Field Museum, Chicago, is exhibited an excellent pair of well crutches from the clifif dwellings of southern Utah (Fig. 7). Dislocation. — The reduction of many of the simpler forms of dislocation was quite generally practiced, both by extension and by manipulation, al- though the methods were of course empiric and without scientific foundation. Treatment of JVounds. — The suturing of incised wounds was a common procedure ; but it was considered so necessary that free suppuration should occur that thin pieces of bark were sometimes placed between the edges in order to check primary union. The sutures were obtained from animal tendons, human hair or plant fibers. The tendons were smoked hard and dry and were not absorbed, but were removed in about a week. It was cus- Fig, 7. Crutches found in cliff dwelling of .southern Utah (Field Museum, Chicago). tomary to provide for ample drainage, which was often facilitated by the insertion of strips of bark or other material. The frequent washing of all sorts of wounds, perhaps several times daily, was universally practiced, and may have had much to do with the rapid, not to say astounding, recoveries that are said frequently to have occurred. The irrigations were made with simple cold water or with decoctions of certain things, such as basswood, willow, slippery elm, lichens and various herbs. In addition, the wounds were often packed with charcoal, ashes, piiion gum and other balsams, or sprinkled with these sub- stances in the form of powder. Most of the balsams and decoctions prob- ably had more or less of an antiseptic action, but it is questionable if this was sufficient to be of much value. Page JUS LEONARD FREEMAN Saliva, both pure and mixed witli other things, was very generally used ; in fact, it was quite the proper thing for a physician to spit on a wound or into the materials used in its treatment. What consternation such a pro- ceeding would produce in the operating room of a modern hospital ! Never- theless, we should not forget that animals always lick their injuries, and that lesions about the mouth heal even more readily than elsewhere. Another revolting custom, according to our point of view, was the sucking of pus out of wounds — a much valued method of treatment. In Brazil, large open wounds of the extremities were sometiines handled in an extremely interesting manner. The part was wrapped in the inner bark of a tree, and suspended on a frame over a bed of glowing coals until nearly roasted. This method was painful, but is said to have been effective, primary union often resulting within a few days under the most unpromis- ing circumstances.^ Although there is little evidence that actual laparotomies were ever per- formed, we at least know, from a description of an operation witnessed early in the seventeenth century by Bernabe Cobo, that they were sometimes "faked" for psychologic purposes. He says: "The sorcerers (medicine- men) did as if they would open him by the middle of the body with knives .of crystalline stone, and they took out of his abdomen snakes, toads and other repulsive objects." However, when we remember with what dexterity the human body was opened for sacrificial purposes by the Aztecs, it should not be surprising if they sometimes performed operations on the internal organs Punctured IVoiinds. — Among the Pueblos, especially, no attempt was made primarily to remove foreign bodies, such as arrow heads ; but they were gradually forced out by firm kneeding and pressure applied to the sur- rounding parts. It was sometimes necessary to continue this painful pro- cedure for several days, although in the end it was generally successful ; but if it failed, an operation was done, through a crucial incision. Irriga- tions with various decoctions were frequently practiced. These were some- times squirted deep into the openings through a quill or a hollow bone by means of the mouth or a syringe made from a bladder. Some of these primitive surgeons used sticks wrapped with cotton to swab out punctured wounds, as part of the general program of cleanliness, which, although they lacked the Dakin's solution, nevertheless reminds one of the methods of Carrel. The cleaning of punctured wounds by sucking out the pus with the mouth was an ordinary and widely spread custom, which undoubtedly pos- sessed merit in spite of its objectionable features. Treatment by Suction. — This was done with the mouth, either directly or through a tube of stone, wood or bone (Fig. 8). In this way pus was liiins ntc;isi<.iii;illy did quite good surgery is evidenced by an iiifl-itiM .1 :m.l i'.iiiprenous foot. The trouble was supposed to .n Tied out for the purpose of dislodging it. ! ncl the bone scraped. The wound was then 1,1 ind bandaged. The final results was satis- 3. That the North Amc. operatio nessed by Cushin h\ due ■rious magK"! A cruci al inci was made, l repeatedly irr icate ■d, packed ^^ factory. Could a RANSOHOFF MEMORIAL VOLUME removed from wounds, ulcere and abscesses, and tlie vascular circulation ])romoted, thus calling to mind the modern suction treatment advocated by Bier. Even the thought of using the mouth directly for such purposes is repulsive, but the danger to the physician was slight and the method was undoubtedly efifective. After all, was it much worse than the many grue- some things done by medical students in the dissecting room? In Bolivia, at the present time, medicine-men have been seen to suck sujipurating wounds and even syphilitic ulcers. Men who were thus willing to sacrifice themselves for the welfare of their patients should be respected and not ridiculed, just as we honor the young physician who heroically applies his mouth to a tracheotomy wound in a case of diphtheria. The imaginary foreign bodies supposed to cause many diseases were also removed by sucking, being first located by the supernatural \ision of the medicine-man — a sort of roentgen-ray eye, as it were. The results were made more tangible by previously placing something in the mouth, such as a stone, thorn, worm or insect, and producing it at the proper psychologic moment. Numerous ailments were held to be due to the presence of bile in the aflfected part. This was sucked out directly with the mouth or through a tube, the surgeon apparently expectorating bile frequently during the pro- cess, being enabled to do so by chewing a species of yellow root in prepara- tion for the occasion. Such procedures were of course nothing but blatant charlatanism, but they had a certain justification in the psychologic efi:'cct which they must have ]iroduced. Cupping. — This was a common remedy. It was done by suction through a buffalo horn or a tube of wood or stone, or even by the mouth alone. Enough force could thus be exerted to cause much congestion, and an expert in the art could even raise a blister. W'et cupping was achieved by a preliminary sacrification of the skin. In the Museum of the State His- torical and Natural History Society, Denver, are some peculiar wooden instruments from the Colorado cliiif-dwe!lings, labeled "use unknown," which might very well have been employed for cupping. They have a hole on one side into which a stem could be inserted to suck through, the body of the instrument being used as a handle to press it firmly against the skin (Fig. SA). Scarification. — This was an almost uni\ersal practice, both for local troubles and those of a more general nature. It was often done with a flake of flint, although more elaborate instruments were in use, ])rovided with many sharp points made of fish spines, flints, etc. A method employed in Brazil was to make a number of cuts in the skin through which was inserted a stone instrument like a spear head, which was moved about in the sub- cutaneous tissues — a mode cf trc-.-ilnicul that could nut have been popular among primitive patients. Page no LEONARD FREEMAN Cauterization. — This was much used. It was acconipHshed with a coal of fire, a hot stone, or by burning a little ball of cotton or other inflammable substance on the cutaneous surface. Among other things, indolent wounds and ulcers were often stimulated by cauterization, and it was also employed as a counter irritant in various painful affections. A favorite method was to burn tobacco or some other material in a tube made of stone (Fig. 8R), and then blow the hot smoke through the tube on the area to be treated, decided virtues being attributed to the kind of smoke employed. Phlebotomy. — This was extensively used in the treatment of local inflammation as well as many general diseases, being considered almost as Fig. 8. .-/, peculiar wooden instrument with cupped end (depth not well shown) .ind with a hole on one side slanted upward, into which a hollow reed could he inserted: possihly used for cupping, by pressing; the hollowed-out end against the skin, and sucking out the air through the reed. /V. clilf dweller's stone pipe, also used for cupping and in the suction treatment of abscesses and suppurating wounds (Museum of State Historical and Natural History Society, Denver). much of a cure-all as it was with our medical forefathers. The vein selected was generally in the leg or arm, but ncc;isionally in the neck or temporal region. The instrument emj)loye(I in opeiiing the vessel was made from a sharp flake of flint or obsidian, a thorn, :i I'lsh spine, or a tooth of some sort in a handle. It was driven with a quick stroke into the vein. In Brazil, a little arrow, made for the purpose, was shot into the \ein by means of a diminutive bow, thus coming as near to a "shotgun prescription" as was pos- sible under the circumstances. Jiiflaiiinuilioiis. — These were lieaU-d i-()i))i))iinly by poultices ntade iwnu plants, leaves or barks (slippery elm, etc.), by cupping, and by counter- RA.VSOHOFF MEMORIAL VOLUME irritants, sucli as the cautery. When an abscess resulted, incision was often resorted to, and tlie contents were aspirated with the mouth, directly or through a tube. Amputation. — Although not extensively jiracticed, amputation was un- doubtedly done at times, the bleeding being checked, perhaps, by the appli- cation of hot stones, as has been observed among the Indians. .\n image on an ancient vase found in Peru distinctly shows the stump of a leg due to an amputation. Hemorrhage. — The use of the tourniquet was undoubtedly understood by some, but the more common method of checking bleeding was by the actual cautery (a heated stone) or by local pressure aided often by such coagulants as spiderwebs and the fine fibers of plants. Hernia. — Many medicine-men knew how to hold a rupture in place quite skilfully with various forms of pads and bandages; but the most remarkable procedure was that resorted to by the Pueblos, who treated umbilical hernia 3 Fig. 9. Corset made oi bark, with liody; possibly used for some ortbopedii Xatural History Society, Denver). r lacing it around the if State Historical and by placing on it a number of large black ants, the bites of which were sup- posed to have a curative effect. It would be interesting to know the origm of such an astonishing idea. Pterygium. — Operations for pterygium were done in both North and South America, the growth being more or less skilfully removed with shatp stone knives. It was probably this operation that gave rise to the erroneous idea that cataracts w'ere removed by these ancient ophthalmologists. LILONARD FREEMAN Artificial Skull Deformities. — The production of these may be consid- ered as a sort of orthopedic surgery* extensively practiced by various North American Indians, as well as those of Mexico and Peru. Sometimes a board was bound against the forehead of an infant and kept there during early growth, resulting in a hideous flatness of the front of the cranium (Flathead Indians). Other tribes, such as the \'ancouvers, Incas and Aztecs applied pads and tight bandages to the head in such ways as to render the skull conical, enormously elongated, or deformed in other monstrous ways. Although producing an outward semblance of idiocy, these pecularities of form did not seem in any way to influence the mentality. Flattening of the occipital region, so commonly observed in collections of prehistoric skulls, was probably more or less accidental and due to pressure of the infants' skulls against the boards on which they were habitually strapped and carried. Anesthetics. — Although it cannot be questioned that some of our primi- tive peoples possessed more or less reliable methods of anesthesia, it is hardly probable that these were very generally known or employed. For instance, the Zunis and some other tribes used for the purpose of substance obtained from the jimson weed {Datura metcloidcs) , containing stramonium. It was administered in sufficient amount to produce indifference to pain or even complete unconsciousness, and in this condition abscesses were opened, fractures set, dislocations reduced, and other surgical procedures accom- plished. In spile of heroic dosage, no serious harm seemed to result. It is quite possible that this and similar methods were also in use among the Aztecs and Incas, who were so closely related in many ways to the Pueblos. In this connection should not be overlooked the strong hypnotic influence imdoubtedly exercised by the medicine-men, with their bizarre make-U])S. weird incantations, and fantastic antics, which were well calculated to make a profound impression on their credulous patients. interesting appliance of bark made to fit the tor!>o and provided with eyrlcts a'; thoiiKh to laic it together in front (Fig. 9). It closely resembles the modern orthopedic corsets used in the tieatincnt of lesions of the spine, and may have been used by the Cliff Dwellers for this purpose or for fracture WOLFF'S LA\\' AND THE FUNCTIONAL PATHOGENESIS OF DEFORMITY.* By Albkrt H. Freiri:k(.. M. D. Cincinnati. Tlie C()rresi)ondencc between the structure of bone, under normal and abnormal conditions, and the calculation.s of graphic statics has been made tlie foundation upon which a doctrine of "functional pathogenesis" has been Isuilt. It has, liowcver. also formed the basis of numerous attacks upon this theory. The theory of the functional pathogenesis of deformity and that of the functional shape of the bones have been made corollaries to the "law of bone transformation"^ by its author, Jul. Wolff. The "law of bone trans- formation" is considered by its author as deriving its greatest strength from the remarkable resemblance existing between the internal structure of the normal human femur and the graphostatic diagram of a Fairbairn crane drawn by the niatliematician, Cullmann. This was given an outline similar to that of the human fennu- deprived of its trochanter major and viewed in coronal section, sustaining a load of 30 kilogrammes. This load is supposed to approximate that which is borne by the femur of an adult and to be ap- plied to the crane in a manner consistent with the conditions in the human subject. The striking analogy between the courses of the bone trabecuke in the frontal section of the femur and those of the trajectories of Cullniann's diagram was first insisted upon by von Meyer. The arrangement of the spongiosa in the sagittal section of the femur, corresponding to the "neutral plane" of the diagram, was foretold by Wolff in conformity with the de- mands of the graphostatic figure, and was substantiated by him later, ana- tomically. After the most painstaking study of the various bones of the body under normal and abnormal conditions \\'olft" was able to formulate his "law," which might be translated as follows : "Every change in the form and function of the bones, or of their func- tion alone, is followed by certain definite changes in their internal architec- ture, and equally definite secondary alterations of their external conforma- tion, in accordance with mathematical laws." Before the promulgation of Wolff's law the generally accepted theory of the development of acquired deformity was that of \'olkinann=-Hueter,'' namely, that consequent upon muscular weakness faulty attitude was as- sumed, in consequence of which one side of a joint — c. g., the external in genu valgum — was subjected to greater pressure than normal ; the opposite side — the internal in genu valgum — sustained less pressure than normal. ■Assuming that during growth the normal development of the joint depends uimn the maintenance of normal conditions of inlra-articular pressure, it was explained that the increased pressure on the concave side interfered with ALBERT H. FREIBERG the normal growth of bone or even caused atrophy of that bone already formed; while on the convex (internal) side the subnormal pressure per- mitted an overgrowth of bone. In spite of the fact that Mikulicz* and Macewen^ showed, quite long ago, that these changes in the articular sur- faces and epiphyses are not constantly present in genu valgum, but that the principal deformity exists in the diaphyses of the femur and tibia, most authors continued, nevertheless, to describe the pathogenesis of this deform- ity in conformity with the theory of Volkmann-Hueter. ^^'e shall later see how it is better explained by reference to Wolff's law and in agreement with the anatomical conditions present. The first corollary which Wolff's theory has associated with it is that of the "functional shape."'"' The external form and internal architecture are determined by function solely. The internal architecture and external con- tour always correspond exactly, the latter representing, mathematically, simply the last curve imiting the ends of the various trajectories which make up the internal structure. The compact substance is to be regarded sinijily as a condetTsation of spongiosa. From the theory of the "functional shape" it is an easy step to that of the "functional pathogenesis" of deformity. If the internal structure and external contour correspond exactly, and if they represent an adaptation to normal function only, then an alteration in static demands made upon the bones must be followed by the proper transformations of structure, both internal and external, and as the result of these we have the "deformity in the narrower sense." The deformity is therefore to be regarded as a physio- logical adaptation of structure to pathological static requirements, therefore to pathological function. The agreement of the structure of bone, both under normal and abnormal circumstances, with mathematical laws, and in particular with those of graphic statics, is insisted upon by Wolff to such an extent that it has formed the basis of attacks upon the doctrine by Bahr' and Ghillini,* as well as others. It is their object to show that Wolff's mathematical con- clusions are erroneous, and that therefore it is not permissible to make deductions from them regarding the structure of the bones in their normal or pathological relations. We may well ask ourselves, on this account, whether mathematical proof of the competency of nature's design in bone structure has been brought bv Wolff in Cullmann's drawing of the Fairbairn crane and the deductions fol- lowing. What is required to enable us to construct the graphostatic dia- gram of the femur? It must be understood, as a preliminary in answering this question, that when "mathematical proof" is spoken of mathematical accuracy is implied. It is by no means enough to say that a striking simi- larity exists between the diagram and the bone whose mechanics we are trying to solve. There must be absolutely no divergence between the two. RAXSOHOFF MEMORIAL J-QLUME In order that the mechanics of the femur shall be submitted to mathe- matical proof, we must know every possible stress to which the bone is to be submitted under normal conditions, and these stresses must be expressed in figures. There must be possible of expression in figures the physical char- acteristics of the material used in the structure. But bones are evidently constructed of sufficient strength to withstand unusual stress without giving way. This fact is demonstrated in every-day life. How shall we calculate this "factor of safety." We may believe, with Wolff, that the femur is burdened like a crane, or with his opponents that this is not so ; but the fact remains that Cullmann's diagram is computed without mention of the mus- cular stresses upon the bone — without reckoning with the stresses put upon the bones in other positions than the upright. The great trochanter has been omitted from consideration altogether. This is obviously not per- missible in a mathematical calculation, because it is always present, because it is the means of transmitting very considerable stress to the femur, and because its internal structure is evidently continuous with that of the upper end of the femur. I am assured by experts that the proper calculation of the construction of the femur upon exact mathematical lines is a work of great magnitude, requiring not only uncommon ability, but, on account of the enormous complexity of the problem, demanding a very large expendi- ture of time. To my knowledge, no such exact mathematical demonstra- tion has yet been made. In addition to this, it is by no means certain that the "factor of safety" could be calculated; this factor might well make the mathematical solution impossible. I'ntil exact mathematical proof is brought, however, there would seem to be no warrant for saying thus definitely that the external contour of a bone represents mathematically the last curve uniting the ends of the various trajectories which make up the internal structure — for assuming that the compact substance is to be re- garded simply as a consolidation of those trajectories coming from the spongiosa. If we are unprepared, however, to acknowledge that a truly mathemat- ical demonstration of the structure of the bones has been made, we are, on the other hand, entirely unwilling to reject the law of transformation and its corollaries on this account without further investigation. In declining to accept the analogy between Cullmann's diagram and the structure of the femur as a truly mathematical demonstration of the latter, we are, further- more, far from saying that if such computation and graphostatic figure were made it would not coincide with the architecture of the bone. On the con- trary, the structure of the femur having been shown by many years of observation to be constant, the similarity between it and the mathematical figure is so striking as to make it .seem reasonably certain that the trabecule do represent lines of force which nature aims to resist by the laying down of the bone tissue. This is, however, far from being mathematical proof, and, as it seems to us, does not afford justification for considering some of I'aiH- IIU ALBERT H. FREIBERG Wolff's other conclusions as "matliematical." however true they may be otherwise shown to be. In view of the necessarily great variation in the factors of weight- bearing and muscular stresses which must exist in mammals other than man — because of the deviation from the erect position of the trunk and because of the participation of the thoracic extremeties in the weight-bearing func- tion, it would seem likely that much information could be obtained from the study of their bones. Able and exhaustive investigation has already been made in this direction by Zschokke,'" Schmidt," and others. It has seemed worth while to independently repeat some of this work as well as to .seek further for information in the structure of other mammalian bones. The femur has been chosen as the bone for further comparison, because of its size and static importance and because it has formed the basis for most of the conclusions which have already been drawn. In examining the femora to be presently described the method reported by Wolff" was employed. Sections were cut by hand by means of a saw. These sections were then photographed by means of the Rontgen ray, and from the negative thus obtained the photographs were made which are herewith ])resented. As is the case with many radiographs, the negative is more instructive than the print made from it. In the smaller femora it was C|uite difficult to obtain prints the finer details of which would lend themselves to satisfactory re])ro- duction. In the description of the specimens which have been examined care has been taken to avoid as much as possible the repetition of details which coin- cide with the descri[)tions of Zschokke and Schmidt, above referred to. The following femora have been examined : I. Ruminantia. (a) Ox. (b) Llama. (c) Sheep. II. Carnivora. (a) South African leopard. III. Primates. (a) r.aboon ( ]japio hamadryas). (m) Orang ( simia satyrus ) . (c) C.ibbon (hylobates). ( Humerus of gibbon also.) For the privilege of examining into the architecture of the femora of the orang and gibbon, as well as the humerus of the latter, I wish to acknowl- edge my indebtedness to the administration of the Smithsonian Institution. Many of the other bones examined have been taken from the museum of the Cincinnati Society of Natural History. RAXSOHOFF MEMORIAL VOLUME REMARKS OX THE SPECIMENS EXAMINED. I. RuMiNANTiA. la) Femur of the Steer. ^Fig. 1.) Relative length of the neck is short. Capital epiphysis extends laterally to a point corresponding practically with the axis of the shaft. It is covered with cartilage to this point, and is to this extent a hearing surface. The angle made by the neck is alxiut 112 lifsrrees. Fig. 1. Femur of ynung adult steer. Arrangement of trabeculre is perfectly constant, and corresponds with the description of Zschokke and Schmidt. The spongiosa of the young adult is composed of exceedingly fine trabeculje. As the age increases the trabecnlae becomes coarser and less numerous, so that the internal structure is more easily read. In old animals this change has continued, so that the difference between their spongiosa and that of the young animal is most striking (see Zschokke). The three most striking systems of trabeculas seen are : 1. Principal pressure trajectories (converging from the mesial part of the head to the adductor compacta). 2. Trabeculje from adductor and abductor compacta arch toward the axis of the bones, forming a series of gothic arches whose apices are in a straight line with the lateral boundary of the capital epiphysis. Such a series of arches also exists in the trochanteric epiphysis. Orthogonal cross- ings can be distinguished in the system of arches. (b) I'eniur of the Llama. (Fig. 2.\ There is practically no neck to the bone. Ca])ital ej^iphysis extends to the axis of the shaft, as in the steer, but the head is set more obliquely, making an angle of 120 degrees with the shaft. Although the animal is comparatively young (shown by imperfect union of epiphysis), the trabeculae are comparatively coarse, their meshes large. The arrangement of gothic arches is lacking. The marrow cavity extends comparatively high into the U])])er end of the bone. There are three systems of trabeculae : Page n& ALBERT H. FREIBERG ^.. Fig. 2. Femur of Llama. 1. Principal pressure trabeculas. 2. Two systems diverging from tlie base of the great troclianler. (a) Toward the head. (b) Downward to the al)duclor compaota. (<■) /•■<•»/»;■ of the Slu-if. ( I'ig. X) In general shape and ])lan of internal structure we have tlie steer's femur in miniature. The angle of the neck is somewhat greater (115 degrees to Fig. 3. Sheep. 117 degrees), otherwise the same arrangement of capital epiphysis and golhic arches, though sometimes not so easily made out. ( Jrthogonal crossings can in part be distinguished. II. Caknivora. (I'ig. 4.) The only specimen examined was the femur of a South African len]iard. The femur is characterized by its pro])ortionalely long, slender, .and some- what curved neck, which makes an angle of 130 degrees with the shaft. The spongiosa is made of plates. RAXSOHUFF MFMORIAL VOLUME The femoral neck presents a triangular cavity of considerable size, and which in position and boundaries would correspond with Ward's tri- angle of the human femur. This is separated from the marrow cavity below bv a small number of arches coming from the adductor compacta and corre- sponding to pressure trajectories. The crossings here are orthogonal. Shorn of the trochanter major the outline is very like that of Cullniann'> diagram; the internal arrangement is, however, very different. III. Prim.mf.s. (a) Femur of Arabian Baboon (Pafio Hainadryas.) (Fig. 5.) The bone is remarkably heavy for its size, and of very dense texture, so that it is difficult to saw. Tlie neck is curved, and makes an angle of about 124 degrees. Baboon. The trabeculae are massive, largely in the form of plates. In the head they are fairly typical as principal pressure trabeculse, and here show ortho- gonal crossings, with a few tension plates. There is here, too, a cavity in the neck, separated by a few plates only from the cavity of the shaft below. The compacta of the shaft is relatively very heavy and thick, so that it is difficult to bring it into comparison with the amount of spongiosa. ALBERT H. FREIBERG (b) Orang. (Fig. 6.) Both in external conformation and internal structure the upper femoral end is strikingly like tiie human. The angle made by the femoral neck is 135 degrees. Both pressure and tension trajectories are found projected in a fairly typical manner, though the reticulum is much coarser than in man. the trabeculae more plate-like. Orthogonal crossings can be made out to a limited extent. The condensation of spongiosa known as the "intermediary epiphyseal disk" (Recklinghausen), and which is constant in the adult femur, is lacking. In general outline the upper femoral end greatly resembles that of the orang and man. The bone is remarkably light, however, its shaft very Fig. 7. Femur of gibbon. smooth and round, reminding one very forcibly of the bones of larger birds. This coiuparison seems all the more apt upon bisecting the bone, because of the relatively large marrow cavity, with no spongy structure whatever save at the extreme ends. The angle of the neck is 140 degrees. RANSOM OFF MFMORIAL VOLUME The section shows a spongiosa of lamellar character, in which it is extremely difficult, if at all possible, to find an arrangement in any way similar to that of man or, indeed, of any of the femora previously described. The neck i)roper is practically free from spongy structure, a cavity being here found which extends to the spongiosa of the head above and to that at the base of the great trochanter below. The cellular spaces of the spongiosa are relatively very large. In view of the contrast in functional importance between the femur and the humerus in the gibbon, great interest must attend the comparison of their internal structures. The result of it is in accord with our anticipa- tion. The internal structure consists of a lamellar spongiosa of compara- tively coarse mesh, but in its general arrangement strikingly that of the human humerus. This is true even to the existence of a place near the great tuberosity in which the spongiosa is quite rare, almost to the degree of being considered a cavity. The remains of the epiphyseal line correspond both in direction and position, and the outline is simply a miniature of the human. (Fig. 8.) In addition, it is to be noted that the gibbon's humerus is, in comparison with its femur, heavier and denser. On holding the bones close to a bright light the shaft of the femur is seen to be quite translucent ; that of the humerus is not at all so. While the humerus is a longer bone, its density is disproportionately greater than that of the femur. The volume of the two bones was determined by ascertaining their displacement of water. This was found to be 25 cc. for the humerus and 22 cc. for the femur. The weight of the humerus was 30.45 grammes against 21.67 grammes for the femur. Their ratio of weight is therefore 1.405, while their ratio of volume is 1.045. It is easily seen that the humerus is an organ of greater strength and usefulness than the femur. In making a general comparison of the specimens in hand, it is well to remember that in graphic statics : 1. The courses of the various trajectories are dependent upon the exter- nal shape of the structures, and conversely, 2. The number of the trajectories and their size depend upon the vary- ing factors of weight and the character of the material. It was remarked by Zschokke — and the statement is to day equally true- that it was not possible to estimate the stresses in bone more than approxi- mately up to that time, but that it was necessary as a matter of scientific reasoning to show, at least in some bones, that the trabeculas truly corre- .spond to the trajectories in direction and strength. Ten years have elapsed since this was written, but the task has not yet been performed. Bahr. Ghillini, and the latter in co-operation with Canevazzi, have offered certain calculations in opposition, but these by no means present the solu- tion which we seek. It would appear, therefore, that we are not yet pro- vided with exact data to attempt a truly mathematical solution of the Page tZZ ALBERT H. FREIBERG mechanics of the femur. If we cling too closely to the mathematical con- cept of bone structure we shall find it impossible, for example, to reconcile the structures in the upper femoral ends of the gibbon and the orang. We have here a striking similarity of outline, with an equally marked incon- gruity of internal formation. If, however, we depart from the strictly mathematical notion and exam- ine into the environment and habits of the gibbon and orang we shall find an admirable adaptation of structure to these and an explanation of the great variation in internal structure. According to Flower and Lydekker,* the gibbon is by nature an arboreal creature of great lightness, accustomed to maintain itself almost entirely by the thoracic extremities. Its movements are extremely rapid, and it is able to project its body through long distances in space in swinging from bough to bough and from tree to tree. When pursued on the ground and unable to reach a tree it moves forward chiefly on its pelvic extremeties, and practically in the upright position, but so awkwardly and uncertainly that it is easily overtaken by man. The humerus of the gibbon, however, belongs to the extremity of greater power and use, and is manifestly of corresponding build. In the orang, on the other hand, we find great muscular power in the posterior extremities and comparative slowness in movement. We may similarly compare the femora of the leopard and the baboon, although possibly not so aptly, the former possess- ing wonderful agility and ability to make enormous leaps, the latter being contrasted by the great muscular development in proportion to its size. Ac- cording to Zschokke, the femora of bears able and accustomed to maintain themselves frequently in the upright position possess great resemblance to the human in their structure. So in the ruminants, also, we find the modifica- tions of internal structure in accordance with the shortness of the femoral neck, adapted, as this is, to weight-bearing purely rather than a large range of motion. From the above we should be justified in concluding that while external conformation and internal structure represent admirable adaptation to use, their mutual interdependence is not so exact as the strictly mathematical concept would require. If we are to modify the doctrine of the functional shape of the bones to this extent, it is probable that the doctrine of func- tional pathogenesis must likewise be qualified. Valuable evidence for the theory of functional pathogenesis should be found where the function of a bone has been changed for a considerable time without any gross solution of its continuity. It is believed that such evidence can be found in the specimen of old unreduced dislocation of the hip which is next presented, and in which we have the advantage of comparison with the normal femur of the same individual. RAXSOHOFF MFMOKIAL I'OLVME Description of Specimen of Old Unreduced Dislocation of the Hif. from the Museum of the Cincinnati Hospital (Series I'll, No. 127 /). The specimen has been in the museum for many years, and all clue to the history of the case has been lost. The board has wired upon it: The Os Innominatum of the Side of the Luxation. This shows the acetabulum to have been unoccupied by the femoral head for a long time. The floor has become roughened by the presence of small osteophytes. The acetabular cavity appears to have become smaller by the thickening of its rim and the formation of new bone in its floor. Just behind the acetabulum there is seen a rather flat, though slightly concave, bone mass of roundish outline, with a diameter of 5 to 3.5 cm., and elevated 0.52 to 0.53 cm. above the surface of the surrounding bone. This rests upon a buttress of bone thrown out from the ilium and ischium. It is evidently the representation of an attempt at forming a new acetabulum. The Upper Hnd of the Right (Dislocated) Femur. (Fig. 9.) This has been sawed through about 8 cm. below the tip of the great trochanter. It has also been bisected in coronal section. The Upper End of the Left Femur (Normal). (Fig. 10.) This has been sawed through at 6.7 cm. below the tip of the great trochanter, the cut just striking the tip of the lesser trochanter. It has also been bisected in coronal section. Upon joining the halves of the right (luxated) femur and attempt- ing to fit the head, in its dislocated position, into the new acetabulum, it is readily seen that its superior surface — that which formerly was the chief means of transmitting weight — was no longer a bearing surface, but that the joint bearing under the new conditions was displaced downward. It can be ALBERT H. FREIBERG seen that the position of the femur could not have been maintained by the bony socket alone, but that the soft parts must have played an important if not the chief role in this. The examination of the femoral head shows at once that it may be divided, functionalh-. into an anterior and posterior, an upper and lower segment. The anteri(jr segment is characterized b)- the smoothness of its external contour and its roundness when compared with the posterior seg- ment, w'hich is rough, presenting irregular elevations. The margin of the head in the posterior segment is considerably mushroomed ; this is not so in the anterior. The corticalis of the posterior segment is very thin, and in one place has disappeared, so that the spongiosa is exposed. (This is not broken.) The head is no longer nearly spherical, but bullet-shaped, with a \ Fig. 10. Xnrnial femur from same subject. rounded apex in the line of the cervical axis. Crossing the anterior seg- ment is a slight ridge which divides the anterior segment into an upper and lower portion. The upper portion is somewhat rougher and flatter than the lower, and this division will be later referred to in the description of the section. From the anterior half of this femur a section was cut varying from 3 to 4 mm. in thickness. A similar section was taken from the left femur. Through a mishap the spongy portion in the lower portion of this section was broken. The spongy tissue should be intact through the section. The following measurements show in part the decided differences existing be- tween the right and left femurs: Diameter from the circumference of the head to the base of trochanter major: right, 8:75 cm.; left, 10.40 cm. Height of trochanter major from tip to base: right, 4 cm.; left, 4.46 cm. Cireatest thickness of adductor compacla : right, 0.58 cm.; left, 0.44 cm. Greatest thickness of abductor compacta : right, 0.57 cm.; left, 0.34 cm. Angle betw-een the neck and shaft: right, 122 degrees; left, 127 degrees. Page ].a RANSOHOFF MEMORIAL VOLUME The following changes of external configuration may therefore be noted : (a) General diminution in the size of the bone; (b) diminution of the angle between the shaft and the neck; (c) alterations in the shape of the femoral head, as before described. The transmutations of the internal structure are. however, more strik- ing, and when taken in conjunction with the above-mentioned alterations of external contour, and in view of the changed conditions of stress from both weight-bearing and muscular action, make it possible for us to present a rational interpretation. These transmutations may be described as follows : 1. The cancellous tissue is of looser mesh than that of the left femur. 2. The tension trabeculse proceeding from the abductor side are shorter in length, but also of changed (shortened) radii. The pressure trabecule, however, seem, if anything, more numerous and of greater strength than those of the left femur. As the result of this. Ward's triangle, which is ordinarily constituted by the convergence of two well-defined groups of trabeculae coming from the upper part of the head and region of the great trochanter, respectively, has disappeared entirely. 3. The most conspicuous change of the internal composition is, however, to be observed in the head. We have here a considerable cavity in the spongy tissue, corresponding in position to the flattened part of the head, and which is traversed by a few bone plates. The antero-posterior depth of this cavity is 2.50 cm.; its width in the coronal section is 2 cm. The antero-posterior diameter of the head at this part is 3.40 cm. The floor of this cavity corresponds exactly with that ridge on the anterior aspect of the head which divides this into an upper and lower segment. 4. I']ion examining the anterior and posterior halves of the l)one, it is seen that the cancellous arrangement in the anterior segment is more com pact. I'nfortunate as it is for the present inquiry that no record is left to siiow the exact amount of motion and strength possessed by this dislocated hip, the changes of its structure nevertheless correspond strikingly with the requirements of Wolff's law. The atrophy of the unused parts, and the condensation of those bearing increased stress, as well as the decided change of external conformation, are sufficiently manifest as to impossibly escape notice. Equally evident, however, are the encroachment upon the original size of the acetabular cavity by the formation of new bone, and the irregular surface of the unused part of the femoral head for the same reason. I take it that we have here conditions analogous to the so-called hypertrophy of the inner condyle in genu valgum, and that we are dealing with an increase in cubical dimensions as an accommodation to altered conditions of space. If this increase of cubical dimensions is to be so regarded it must be looked upon as a result of the deformity and not as one of its causes, lis functional role in resisting stress can. fnun it> physical characters, be considered insig- nificant. ALDTiRT H. FREIBERG From the researches of Wolff, Zchokke, Schmidt, and others, as well as from the observations herewith presented, it is believed justiliable to con- clude as follows : 1. The strictly mathematical concept of Wolff's law has not yet been justified by demonstration. 2. vSave in their mathematical aspects, the statenienls of Wolff's law and its corollaries may be accepted as being in agreement with observations hitherto made. 3. If we accept the foregoing statements it does not follow that we must make use of the so-called "functional methods" in our therapeutic endeavors ; they are to be chosen not for theoretical considerations only, but for reasons of expediency and practicability. [Note. — In the discussion following the reading of this paper there was presented the right femur of an idiotic woman, thirty-five years of age, by Dr. R. Tunstall Taylor, of Baltimore. The specimen is of such interest, and is believed to be corroborative to such a degree, that, with Dr. Taylor's kind permission, the case and section of the bone are herewith briefly presented. The subject from whom it came was a paralytic, considerably deformed, having severe scoliosis and being greatly underdeveloped. The fibula of this subject was about 15 inches long and somewhat greater in thickness than a good-sized knitting needle. The pelvis was likewise deformed. The femur is extremely light in weight. Its extreme length is 38 cm. ; the coronal diameter of the shaft at the middle is 1.3 cm. The head is greatly flattened from above downward, as may be seen from the section. The surface is marked by several deep groo\es of antero-posterior direction. Otherwise the bone is of fairly normal shape, with the exception of the trochanter minor, which forms a quite long spur projecting anteriorly, leaving a deep groove between it and the upper part of the sliaft. The radiogram of the section of the upper extremity of this femur is almost self-explanatory. / if femoral head o i a paralvtic idiot , awed (By permission of Dr. R. T. Tay lor.) Section (Fig. 11.) \'estiges of the normal internal struclurc arc a]»parent. Such are the intermediary epiphyseal disk, some of the princijjal pressure trajec- tories, and some of the arches as well. The upper end of the bone is, how- ever, merely a hollow shell, and expressive, it seems to me, not only of imper- Pagc in RAXSOHOFf MfiMORIAL VOLUME feet development, but of general atrophv also. As tar as can be ascertained, this person was never able to maintain the upright position.] Wolff. Gesftz. d. Transformation d. Kochcn. Berlin. 1892. Volkm.-,nn. v. Pil iha 11. Billroih-s Chinircie. i i., Ahth . IJ. p. 693 ct scq. Mufter . Virrhow ■s Arrhiv. XXV. p. S72 et «p a. Mikulii Jfacew; :z. Arch, an. Lancel f. klin. Chir., xxiii. p. 561 t, Septemhcr. 1884. Wolff. Loc. cit.. p. sn. Rahr. Zcit=cl,r. f . Orth, Cliir.. V. p. 52. 295; ; Band. p. 522. Chillin; i. Zeit=chr . f. Orth. Chir.. VI. p. 589: ; ix, p. 178. Wolff. Berl. klin . Wochenschr,, 1900, No. 18. Zschokke. Weite re I-ntersuchuneen ueber das \- d. Kn Schmidt. Zeitschi r. f. Wisscnsch. Zodlogie. Ixv. p. 65 e t seq. Wolff. Arch. f. 1 klin. Chir.. Band liii. Heft Wolff. T-phpt d. Wech-^plheziehunEen zw. d. Form u .d. Functi on d. e nus. I.e ipzis. 1901. zetnen Gebilde d. THE ATROPIN TEST IN THE DIAGNOSIS OF TYPHOID INFECTIONS.* Aij'RED FkiI'Dlander, M. D. (Cincinnati) and Cakicv p. :\IcCord, M.D. (Detroit) Chiefs of Medical and of Laboratory Strviro. respcclivcly, Base Hospital Camp Sherman, Chillicothe, Ohio With all appreciation of the minimizing effect of typhoid-paratyphoid prophylaxis on typhoid infections in army camps, it is still reasonable to anticipate the occurrence of occasional camp cases. The larger numljer of such cases will probably arise from among unvaccinated civilian wurkmen and from the improperly vaccinated soldier. In typhoid infections ap])earing in persons who have received typhoid prophylaxis completely or incompletely, the disease will usually be characterized by such mildness as not to present the outstanding features of typhoid that so readily permit a diagnosis among the unvaccinated. Facing this difficulty in the recognition of typhoid exist- ence, those medical officers responsible for the prevention of infectious diseases in army camps, and those on whom will devolve the care and treat- ment of suspected cases, are evaluating all recent developments purporting to be of additional diagnostic aid. At a similar period in the making of the British Army there came into use the atropin test as a means for the detec- tion of typhoid infections. The British Medical Research Committee has sanctioned this test's reliability to the extent of issuing a monograph on the subject, prepared by Marris.' In this hospital up to the present time no cases of typhoid have occurred; but in order to be conversant with the merits and technic of the atropin test against the contingency of typhoid outbreak, 228 cases of diverse diseases other than typhoid and paratyphoid have been tested in the manner described by Marris. The results form the basis of this report. THE KATIOXALE AND TECHXIC OF THE ATROPIX TEST. According to the sponsors of this test, the normal individual or the patient ill of diseases other than typhoid infections responds to the administration of atropin with a noteworthy increase in heart rate. In typhoid patients, however, this acceleration either does not occur or occurs to a lessened degree. This difference is attributed to an antagonism of action between the alkaloid and the toxins produced by the organisms of the typhoid group. This relative lack of response to atropin is the basis of the test, the applica- tion of which is as now noted: The patient Hes horizontally and is instructed to remain completely at rest through- out this test, which is not employed until at least one hour has elapsed from the last meal. The pulse rate is counted minute by minute until it is found to be steady ; ten Troni The Journal of tlie .\i 1. Marris, F. A.: Use of A' Infections, Brit, Med. Jour., 1910, RAXSOIWFF MEMORIAL VOLUME minutes of such counting usually suffices. Atrophin sulphate is then injected hypoderm- ically in the dose of 1/3^ grain, preferably over the triceps region to insure rapid absorption. An internal of twenty-five minutes is allowed to elapse, and the pulse rate is again counted, minute by minute, until it is clear that any rise which may follow the injection has passed off; fifteen or twenty minutes may be necessary for this purpose when the pulse rate is raised at the first count. If, for example, a near constant pulse rate of 70 was exhibited at the preliminary counting, and a maximum of 96 was exhibited at the pulse rate subsequent to atropin injection, the inference after this acceleration of twenty-six heats per minute would, under the provisions of the test, be that the condition was not typhoid. If, however, the rate after atropin had attained only to 78 beats per minute as the maximum, the inference is tena- ble that the existing condition is one of the typhoid group. The test does not discriminate between typhoid and paratyphoids A and E. In Marris' report, the line of demarcation for the interpretation as existing typhoid or nontyphoid is placed at fifteen ; that is. if the acceleration following atropin is less than fifteen beats per minute, typhoid is indicated; if the increase is fifteen or more per minutes, typhoid is not indicated. A "positive" atropin reaction is one giving rise to little or no increased heart rate after atropin administration ( fourteen or less per minutel. A "negative" reaction is one giving rise to an increase of fifteen or greater. If the patient is admitted during the first fortnight of his illness, the test is applied as soon as possible after admission and is charted with the temperature. When a posi- tive reaction (little or no response to atropin) is obtained, the diagnosis of infection with a member of the enteric group of organisms may be made. In the case of a nega- tive reaction, the test should be repeated after two or three days, and if again negative, it is again repeated. Three negative reactions falling within the first fortnight of the illness exclude the presence of typhoid with a considerable degree of certainty : there are rare exceptions, and in these a continuation of the test is usually suggested by the symptoms and remaining clinical signs. 4|,|.|3| ' 5 t 7 ~r ~~n"y t^MV-H, t7 At u\fi PUL5 -Ml 1 1 1 1 _-. ^ 'z ■m Ei._ |_ ^^ -?r- ■"■^ =E=i *:5 Chart 1. Typical positive atropin test in measles patient presenting clinical mani- festation similar to those of the patient whose reaction is shown in Chart 2. The broken line after the administration of the atropin represents an interval of twenty- five minutes. In the normal individual to whom has been administered 1 30 or 1/33 grain of atropin, some or all of the following manifestations may be expected to occur: A slight and transient decrease of the pulse rate (two or four beats per minute) occurs early with a return to normal. This is followed by a rapid increase in heart rate of from twenty to thirty-five beats. The height of this acceleration is reached in about one-half hour, slowly returning to normal in one or two hours. The classical characteristics of atropin action, lessened secretions and dilated pupils, seldom are observable during the Page IM ALFRED FRIRDLAXDRR AND CAREY P. McCORD testing period, but at times may be noted witbin an hour or more subsequent to the testing. Marris' report records 111 cases of typhoid inffttions in which a diag- nosis was definitely established through the isolation of the organism from blood cultures. The atropin test was accurate in 98 per cent. In these cases the pulse acceleration averaged only 6.6 beats per minute. In another group of patients observed by the same writer, of 247 diagnosed by the less defi- nite agglutination method as having typhoid, 222 reacted accurately to the test. Agglutination as a diagnosis procedure has become of less value be- cause of frequent agglutination concomitant to typhoid prophylaxis. MINJo 1 Z 3 4 5 ■. 7 » 9 10 JSJt 37 3«39-W ♦< -"i -13 «-«3 * -l? 1» 49 Jo '6 _ \ t it n t t - : 7 , ^ « \ t^ % ' I u 1 « - i 76 i « i 71 D if fL u. ^ (.4 / tz / K ^g^^^^ __._.._ Cliart 2. Typical ne fcstation similar to thos n test in measles patient presenting ;-nt in Chart 1. At the Royal Victoria Hospital in Montreal, Mason- made use of the atropin test as a diagnostic aid during an epidemic of typhoid infections. The technic employed was essentially that described by Marris. In ail, 265 tests were made in sixty-three cases of typhoid or paratyphoid. Fifty-six of the number were cases of typhoid fever established by positive blood cultures or liy W'idal reactions in dilution higher than one in forty. Five of the cases were paratyphoid B, diagnosed bacteriologically, while the re- maining two cases were clinically typhoid but the diagnosis was uncon- firmed by any bacteriologic or serologic findings. Of the total number (sixty-three patients), fifty-seven were males and six were females; no sex variations were observed. Eleven of the sixty-three failed to give a posi- tive reaction to the atropin test. This departure from the anticipated posi- 2. Mason. E. H.: The \ alue of the .Mropin TcM in Ihe Diaenosis of Typhoid Kever, Arch. RANSOHOFF MEMORIAL VOLUME tive reaction is attril)iited by Mason to be due in part to the fact that in cer- tain cases only one test was carried out, in part to the restlessness of some of the patients under test conditions. The reaction became positive about the tenth day and disappeared about the thirty-first day of the infection. As a check for these known typhoid and paratyphoid cases, the test was applied to forty-six patients suffering from various clinical conditions other than the typhoids. Forty-three yielded the anticipated negative reaction, averaging in cardiac acceleration 21.5 beats per minute. Three gave positive ™ 1 U 3 + •^ '■M^ ^ -'kK4kM+hkhhH+ ' ■ '^""■ 1 \r^^^ 102 L M -^ --^;£:.^4--l-UffllllllllM- Chart 3. Typical positive atropin re clition was the same as that nf the pati< five minutes ion in pneumonia patient whose clinical con- in Chart 4. Broken line, interval of twenty- reactions without any probability of enteric infection. Mason concludes that in the diagnosis of fevers of the typhoid group, the atropin test is of distinct value and in many cases afifords diagnostic data prior to a positive W'idal reaction. TECHXIC.VL DAT.V FROM THE PRESEXT TN\'ESTlG.\TIOX. Early in our series of tests it was obvious that our results would be at variance to the foregoing, for which reason it was deemed desirable that our technic should conform in as many respects as possible to the previous work. This necessitated the discarding from our .series the results from fifty-eight cases in which technical innovations had been introduced. In the remain- ing 170 cases, 198 tests have been carried out with rigid adherence to the Marris technic. The patients on whom these tests have been made were all men, predominantly of the third decade. All had received typhoid-para- typhoid prophylaxis. These men were patients suffering froin the diverse conditions given in the accompanying table. In one group of 170 cases, 108 (63.6 per cent.) were sensiti\e to atropin (atropin negative test), while sixty-two (36.4 per cent.) were nonsensitive to atropin. giving the reaction described as typical for typhoid infections. Neither the positive nor the negative atropin tests were sharply associated with any particular condi- tions. It may be observed in the table that in the various listed processes, the ])ositivc and the negative are almost unitormly distributed in the ratio.s noted above. Charts 1 and 2 are records of the occurrence of distinct posi- tive and negative atropin tests, respectively, obtained in two measles cases similar in clinical characteristics. Charts 3 and 4 likewise were obtained, respectively, in two cases of lobar pneumonia of approximately tlie same degree of severity and at about the same stage of the process. Page 133 ALFRED FRIEDLANDER AND CAREY P. McCORD -.l.l. .3 ,. 1 s ™l" """=333 PUL^SE -^ 1 ,•■•' A III ^ !^-i / , IIA - 1^ III 1 /M " i 101 s 1 ICX. a im " I IJ2 I ICO J/. 1 V " I 91. : 2 t 5 90 12 is_ nS- .,„ \T\1 ~-^i fY \4Jr. >■--■> ^ -•--. Chart 4. Typical negative atropiii re condition was the same as tliat of the patii :ion in pneumonia patient wliose in Chart 3. On two successive days the atropin test was tnade on twenty-seven patients thus distributed: influenza. 11; pleurisy, 3; pneumonia (lobar), 2; ])neumonia (bronchial), 1; Ijronchitis. acute, 4; tonsillitis, 5; ethmoidilis, 1. RESULTS OF TESTS. Total Number of Cases Measles Scarlet fever Influenza Tonsillitis Laryngitis Pharyngitis Bronchitis Pneumonia Pleurisy Bronchopneumonia Mumps Mumps-measles Meningitis carrier Diphtheria carrier Diphtheria Ethmoiditis Neuritis Adenitis Gastric ulcer Intestinal stasis Hyperchlorhydria Arthritis, chronic Tuberculosis, pulmonary Jaundice, catarrhal Tapeworm Heart block Hyperthryroidism Secondary anemia Total 18 6 12 23 19 4 S J 3 T 5 1 22 13 9 1 ^j 9 2 6 3 4 I 1 1 1 1 1 1 1 RAXSOHOFF MFMORIAL VOLUME It was observed that of the total number, fifteen patients were atropin sen- sitive on both days, four were atropin nonsensitive on both days, and eight were within the limits of atropin positive on one day and atropin negative the other day. The last named group of eight may not be cited as evidence of shifting from an atropin sensitive to an atropin non-sensitive state, for the pulse rate changes were such as to fall in one day's test just above or just below the arbitrarily chosen line of demarcation, and on the following day to fall on the opposite side of the line without there having occurred an actual pulse rate variation of more than six or eight beats. Apart from these borderline cases, the results obtained on the two successive days were closely alike, as shown in the plotted results in one case (Chart 5). In none of the sixty-two cases giving rise to results that under the \ivo- visions of the test would be interpreted as typhoid infections were there evidenced any clinical or laboratory findings that might remotely be attrib- uted to typhoid or paratyjihoid fe\er. /«tliy|o 1 z 5 4 5 b 7 8 <> ,o^Xi^,3^3^i9'u^4 *^^i'^*^s'<^^■, it A^ i^ pur^E ■■■■■- " Y ,, '« \ s^ ^ ». ^ '" " ( ^ t ^ *^^*- '" ■ 7 s^^^ ^ - "^«.2 ^ no ^ 114 ' I'l 1 110 1 lOi '/ ""■ ' f '"* /jaGrtiTiAtropilSu >h»»« 5^ " ICZ \ i" J_ " ^ ^ ^ S 1 » ~^^& f^^zli * ^%S ^^* ^ ^ - i ^v' 4 '^ > 1 " : Chai ' days Conformity of results of two negative atropin reac patient convalescing from lobar pneumonia. CO.MMEXT. The conception of a specificity of antagonism of action between atropin and typhotoxins is in no way borne out by the results of our investigation. The occurrence of 36.4 ])er cent, positive atropin reactions in a series of 170 nontyphoid cases removes from this test all but the most casual signifi- cance as a diagnostic procedure. The factors that determine the degree of response of the heart to atropin action are fundamentally the outgrowth of variations in the equilibration of the vegetative nervous system. This lack of sensitiveness to atropin is not peculiar to typhoid infections, but is detect- ALFRED FRIEDLANDER AND CAREY P. McCORD able in many diseases and, in fact, may frequently be elicited in normal individuals as a mark of vegetative nervous system instability. Not only in other conditions than typhoid is this insensitiveness to atropin encountered ; but also in typhoid infections marked cardiac acceleration may ))e observed, according to Matsua and Murakami, ■* who say : "In our forty- six cases of typhoid fever (including seven cases of paratyphoid B), atropin was quite active, accelerating the rate of pulse, especially in cases of brady- cardia. As all our cases were serologically and bacteriologically controlled, the diagnosis was undoubtedly correct." It is noteworthy that such typhoid ])atients as exhibited a bradycardia exhibited cardiac acceleration after atropin, while the patients presenting a relative tachycardia were for the most part unafifected by atropin. In the series cited by Matsuo and Mura- kami, all the fatalities occurred among the number giving positive atropin reactions. This observation is in keeping with the well established fact that a tachycardia in typhoid bespeaks a pessimistic prognosis. The atropin re- action for this reason may attain to definite prognostic value. SUMMARY. A series of 170 nontyphoid patients has been tested with the atropin reaction in the manner described as reliable for establishing the presence or absence of typhoid or paratyphoid infections. Thirty-six per cent, of the number examined yielded results characteristic of typhoid. Those cases giving reactions typical of typhoid without any evidence of typhoid existence were distributed over thirteen diseases. It is concluded from so high a percentage of discrepancies that the atropin reaction is witliout esjjecial value in the detection of typhoid infection. NOTE ON THE INFLUENCE OF FOOD UPON THE INTESTINAL FLORA OF INFANTS.* Rv Alfrrd Friedlander, M.D.. AND J. \rCT()U C.KKKNEBAUM, M.D., Cincinnati. As a preliininaiv to the .studies about to be reported, routine stool ex- aminations were made on fifteen marantic infants, all under one year of age, in the children's ward of the Cincinnati Hospital. The following schedule was observed : The stool in each case was collected on sterile gauze, marked and placed in an ice pail till examined, the time varying from thirty minutes to twelve hours. Every stool was examined macroscopically (size, shape, color, con- sistency, abnormalities, such as curds, mucus and blood). Microscopically, fats, neutral fats, fatty acids, soaps, starch, crystals, abnormal constituents such as cells.' A Gram smear was then made and inoculation made into the various media to be mentioned. This technique was followed in all cases except that in the study of the two special cases the stool was collected by means of a sterile anal tube after the method of Kendall. - Routine examination for the bacillus aerogenes capsulatus (B. Welchii), according to the methods of Herter^ and Kendall,* showed conclusively that the gas bacillus was not a common or a constant factor in the cases studied. Forty-six tests were made in the twelve children, five cases showing a posi- tive reaction for a total of eleven positive finds. The two cases subsequently selected for special study had seven of these eleven positive reactions. Tests for dysentery, typhoid and paratyphoid were negative in all cases. The two special cases showed practically the same clinical picture, and, though of dififerent ages, were taking approximately the same kind and amount of food. Their stools were similar, macroscopically and microscopi- cally. They both presented typical marantic pictures. In both cases various food modifications, for the most part containing high percentages of maltose, cane sugar or lactose, had been tried. Neither case had done well on these mixtures. It appeared to us of interest to study the intestinal flora in these two cases in detail, attempting to ascertain whether definite change in the bacterial picture could be brought about by change of food. This method of studying the biology of the intestinal flora was similar to that adopted by Kendall"' in his work upon monkeys, from which he deter- mined that putrefactive flora developed on a proteid diet, acidophilic on a carbohydrate diet. Accordingly, these two children, after a complete series of examinations of the iiUestinal flora had been made, were given Finkel- ALFRED FRIEULANPER AND J. VICTOR GREEN EBAUM stein's albuminized milk." The formula of this food is approximately fat. 2 per cent.; sugar, 1.5 per cent.; proteid, 3 per cent. Each child was given seven ounces every three hours — six feedings in twenty-four hours. The forty-two ounces for each child daily gave a caloric value of 498, and supplied 6.4 grams nitrogen. We selected this food for the following reasons: ( 1 ) The children had both done poorly on food with higher sugar con- tent. (2) For the well-known therapeutic effect of lactic acid bacilli in cases showing presence of gas bacillus (which both these children had done). (3) To obtain the high proteid in proportion to sugar content. (4) To determine the effects clinically, and from the standpoint of in- testinal flora biologically, upon cases for whom a priori such food might be considered indicated. After the children had been upon this albuminized milk for three weeks, complete series of bacteriologic tests were made at intervals of a week, using stools collected by the anal tube for this purpose. Daily examina- tions of stools collected in the ordinary manner (sterile gauze, ice pail) were also made. The day after the .second anal tube specimen was obtained (the children had been on the Finkelstein milk for four weeks) the food was again changed. The children were now given a mixture containing ap- ])roximately fat. 2 per cent. ; sugar, 7 per cent. ; proteid, 3 per cent, made by modification of certified milk.* Each child was given seven ounces of this mixtures every three hours — six feedings in twenty-four hours. This food has a caloric value of 791, and a nitrogen content of 6.4 grams. This food was selected because : (Ij The children, though in better general condition while on the Finkelstein diet, did not show a sufficient increase of weight. An increase of the caloric value of the food was thus indicated. We chose to increase the sugar, using lactose, because from our experience in the Cincinnati Hospital and the Boston Floating Hospital we had not found the lactose as injurious as the Finkelstein school would make it out to be. Besides the children had previously had other sugars without good effect. ( 2 ) To replace the salts which the Finkelstein food reduces. (3) Because examination now .showed absence of gas bacillus, so that excessive amounts of lactic acid bacilli were not needed. The same observations and bacteriologic tests upon specimens obtained with the anal tube were made, after the children had been taking the food for three weeks and were repeated one week later. As before, daily ex- aminations of stools obtained in the ordinary way were carried out. The routine bacteriologic tests carried out in both cases consisted of in- oculations of fermentation tubes of sterile milk, broths with 1 per cent, each of saccharose, dextrose and lactose ; 2 per cent, dextrose, with 0.6 per RANSOM OFF MFMORIAL VOLUMF cent., or "/,„, acetic acid, and 1.2 per cent., or "/_-, acid, aerobic gelatin stabs, miik and litmus milk test tubes, anaerobic gelatin test tubes (Wright's method), and both gas bacillus tests were made daily. Gram smears of the fermentation tube sediments were made at the end of five days. The de- tailed bacteriologic fiindings, together with details as to chemical and niicro- sco])ic examinations of the stools, are attached to this report. The condensed report of the two cases follows: C.'\SE I. Hazel Reed. Aged eight months in November, 1911. Admitted to hos- pital August. 1911. Diagnosis at that time, gastroenteritis. Typical atrophic picture. PijRion I. Entrance to November 18, 1911. Foods Used. — Various modilications of milk and barley water, formulae containing high percentages of maltose, cane sugar and lactose. General condition during this period changed but little. On entrance weight was seven and one-half pounds. There were occasional slight gains, but the general trend was downward until at the end of the period the weight was six and one-half pounds. Temperature practically normal throughout the period. The stools averaged one to two per day, soft to pasty green, with occa- sional curds and mucus. They showed fatty acid crystals in abundance. Gram fecal smears : Gram negative always with one exception. 'i\vo pre- sumptive reactions for gas bacillus out of five tests. Period II.' November 18. 1911, to December 20, 1911. Food Given. — Albuminized milk (Finkelstein). Slight but steady gain in weight to eight pounds, a gain of l.i pounds in four weeks. The tem- perature remained normal. Urine showed no indican. The stools averaged one per day, constipated, grayish-yellow, no curds. Microscopically, some fatty acids and crystals. Reaction, alkaline. Gram fecal smear: Gram negative predominate. Gram positive once. Bacteriology. — Stools collected in ordinary way. Two presumptive gas bacillus tests two and three days after the food was begun, negative after that. Considerable activity in milk. (Stormy fermentation.) Gelatin: Considerable liquefaction and gas. Litmus sugar and broth test tubes=acid and occasional gas. Anal tube stools : Considerable activity in all media. See summary in chart. Period III. December 20. 1911. to January 15, 1912. Food. — Certified milk modification. Fat, 2 per cent.; sugar, 7 per cent.; proteid, 3 per cent. General condition strikingly improved. Rapid gain of weight, one-half pound in first four days. Total gain of 2.4 pounds in twenty-six days. Temperature practically normal throughout the period except for one period of thirty-six hours. The lower incisor teeth appeared at this time. Stools, one to two daily, soft to pasty yellow with occasionid curds (proteid by formalin test). Fatty acids and crystals. Page m ALFRED FRIEDLANDER AND J. VICrOR GREENEBAUM Gram fecal smears : Negative predominate. Hactcriolngy. — No presumptive gas bacillus tests. Somewhat less activ- ity in milk and gelatin, liquefaction present but decreasing. Anal tube stools: Somewhat less activity in media, liut same types of re- actions were present. See summary in chart. We had thus definite and striking changes in the general condition and weight of the child and in the gross character of the stools in both tlie second and third feeding periods. (Albuminized milk and modified certified milk.) The improvement was much more marked in the < If m .11 sfl iBil |gjl i. illl ii; 3 11 mi iifi iili w M 1 IS I'll 1 11= 1 5j i 1 1- 1- lis i? 1 illp ' ' ' 11 + 1 !■ p -J 1'" ALFRED FRIED LAN PER AND J. VICTOR GREEN EBAUM Period III. December 20, 1911, to January 15, 1912. Food. — Modified certified milk, fat, 2 per cent. ; sugar, 7 per cent. ; pro- leid, 3 per cent. General condition strikingly improved. Child gained three pounds in twenty-six days. Temperature normal, practically during whole period. Stools, one to two daily. Pasty, yellow, soft, with occasional curds. Reaction, alkaline. Microscopically, alnmdant fatty acid crystals and soap. Gram fecal smears: Gram negative with increased numbers of Gram positive or- ganisms ; Gram positive three times. Bacteriology. — No gas bacillus reactions. Very little reaction in the milk test tubes, very moderate reaction in gelatin. Anal tubes specimens showed activity on all media, but in general less than that seen in Period II. (Summary on chart.) The child was discharged in excellent condition. We had in this case distinct improvement in the general condition, weight and gross character of the stools in both the second and third periods, though the changes were much more marked in the third period. There were no striking changes in the bacteriologic reactions, though there was some decrease in activity in the third period. The Gram fecal smears, however, took on a decided positive appearance in the third period. There were no gas bacilli reactions after the third day on Finkelstein's diet. SPECIAL NOTES REL-ATING TO BACTERIOLOGIC FINDS NOT CHARTl'.D ABOVE. Milk Fcnncntation Tubes. — Same type of reaction with both foods. Gram Smears. — Gram -|-. Occasional branched forms (probably bacillus bifidus) on both foods, Predominace of yeasts on Finkelstein's food. Milk Test Tube. — Distinctly greater activity (coagulation gas and diges- tion) in Period II. (On Finkelstein's food.) Aerobic Gelatin. — Marked activity (complete liquefaction) in first test, but second test in both cases on Finkelstein's diet showing slighter reaction than in either of tests on 2-7-3 food. Anaerobic Gelatin. — Same as in aerobic gelatin except in general less activity. No liquefaction present on second test on Finkelstein's food. FERMENTATION TUBES. Lactose. — All tubes showed cloudiness and gas. Average gas production in centimeters somewhat more in Period II (Finkelstein) than in Period III (2-7-3). Smears of sediment branched rods (probably bacillus bifidus) present in both foods (greatest number on Finkelstein's food). Many yeasts present in this first test. (Yeasts constantly present in fecal smears in both cases.) Dextrose. — All tubes showed cloudiness and gas. Average in centimeters greater on Finkelstein's food than on 2-7-3. Most gas produced in this sugar, although only slightly greater than in lactose. Branched organisms RAXSOflOFF MEMORIAL VOLUME (prubabl}- bacillus bifidus ) jJreseiU on botli foods, yeasts present on both foods. (Greatest frequency on this sugar.) Saccharose. — All tubes showed cloudiness and gas, .Slightly greater amount in centimeters on Finkelstein's. Least amount of gas produced on this sugar. Branciied forms (probably bacillus bifidus) present in all the tests. Yeasts present in considerable amounts on both diets. "/,„ Acetic Acid: T2V0 Per Cent. Dextrose. — Question of cloudiness on both diets. Small number of bacteria in smear. About the same types con- stantly present. \'arious sized Gram positive rods and diplococci and Gram negative rods and diplobacilli present. Yeast very rarely seen. "/-, Acetic Acid: Tiuo Per Cent. Dc.vtrosc. — Question of cloudiness on 2-7-3 diet. Few bacteria, as a rule, seen in the smears. Occasional yeast l^resent. Gram positive various sized rods, diplococci and diplobacilli, and Gram negative rods and diplobacilli present. Branched and knobbed rods (Gram negative) appeared in Period III in Lizzie's tubes. Spore-bearing rods present in one test of Hazel's in Period III. (Trt.s- Bacillus Test. — Negative on both foods. ( B. Welchii.) (The non-correspondence of the Gram smears of the .sediments with each other and with the fecal smears agrees with the findings of Hcrter and KrndalF rin this ]ioint. ) GE.\"Er^-\L CONCLUSIONS. (1) The foods used, albuminized milk and simple modified milk (fat, 2 per cent.; sugar, 7 per cent.; proteid, 3 per cent.) had very little influence on the biologic reactions of the fecal flora as a whole. There was. however, a slight lessening of the putrefactive reactions on the 2-7-3 modification. The acidophilic flora remained about constant on both foods. (2) Finkelstein's food is buttermilk with the salts and sugar reduced and a high percentage of finely divided proteid. To a great degree the beneficial effects of the food depend upon its lactic acid content, and in giving the food we are really using lactic acid therapy. The lactic acid bacillus flora formed during its administration was continued when the food was changed to 2-7-3, because in the latter instance the lactic acid was formed from the sugar. In other words, with both foods lactic acid therapy was given, so that it is not surprising that the bacteriologic reactions were similar in both instances. (3) In striking contrast to the slight changes in the intestinal flora there was a remarkable change in the clinical aspect of the two cases. The general condition improved greatly, as did the gross character of the stools. On the Finkelstein food there was moderate but steady gain in weight, while on the 2-7-3 modification there was very marked and rapid gain in weight. (4) The Finkelstein food was undoubtedly of marked value in both these cases. After its administration the gas bacillus disappeared in each case. Again the low sugar content of the food undoubtedly rested the gastrointestinal tract, so that after four weeks of its use an increase of sugar Pauc r,.: ALFRED FRIED LAN PER AND J. VICTOR GREENEBAUM ad inaxiiiiuni (7 per cent, lactose) was not only tolerated, but utilized with great benefit to the child. (5) Finkelstein's food is undoubtedly of great value for short periods in suitable cases, for its effect upon the intestinal flora (substitution of acido- philic for putrefactive organisms) and also because of its power to rest the gastrointestinal tract by its low sugar content, especially for cases previously overloaded with sugars. Our thanks are due to Dr. W. B. Wherry, Professor of Bacteriology, University of Cincinnati, for his helpful suggestions and kind supervision of the bacteriologic work. REFERENCES. 1. Talbot: .\rchivc5 of Pediatrics, Febn.arv, 1911. 2. KeiKlall: Boston Medical and Surgical Journal. March 2. 1911. 3. Herter: "liacterial Infections of the Dipestive Tract." 1907. 4. Kendall and Smith: Boston .Medical and Surgical Journal. -March. 1911. 5. Kendall: Journal of Biological Chemistry, 1911, \ol. \'I. p. -199. 6. Leopold: .'\rchives of Pediatrics, August, 1910. 7. Herter and Kendall: Journal of Biological Chemistry. 1908-1909. \u\. \ . p. 2W. TUMORS OF THE MEDIASTINUM.* By \V. D. Haines, M. D., Cincinnati. The classification of tumors is one of the most changeahic and unsatis- factory chapters in surgical pathology ; each text-book contains a different classification and each author, like the housewife with her sewing machine, thinks he has the best ; there is, however, an encouraging note in the wide discrepancies contained in books published within the quarter of a century just passed, in that with the increase of our knowledge concerning casual factors in the production of tumors there has come a gradual diminution in the number of morbid conditions formerly known as tumors. This better comprehension of production of tumors has resulted in the combining under one head of a number of conditions which were formerly considered as inde- pendent. Uppermost in this evolution is the recognition by investigators that tumors are made up of tissues normally present in the human body; i. e.. the new growth is but a new arrangement of old structures. This does not imply that the new growth is made up of tissues identical with its immediate surroundings, but that the component parts may be found existing normally in the body — chondromata occurring in glandular tissue, dermoid cysts of the ovary and numerous other examples will come to mind wherein totally unlike- "foreign" tissue has been found in tumors, but upon examination we find such foreign tissue exists as such elsewhere in the body, and we leave to the imagination the task of explaining the presence of such tissue in an imusual location. By far the greater number nf intratlioracic tumors are located in the mediastinum, save aneurism, nearly all of theni have their origin in the glandular tissue contained in this space. Neoplasms of the chest occurring outsid the mediastinum usually involve these spaces in the course of their development. While it is manifest that the site of the tumor will dominate the clinical manifestations which occompany its development and determine the line of treatment to be instituted, still more importance attaches to de- termining the true nature of the growth and the effect it will probably produce ui)on the surrounding structures. The scheme of diagnosis, therefore, should include careful consideration of the early and more or less obscure symptom; embracing muscular pains, irregular heart action, difficulty in breathing or swallowing, spasmodic affections of the laryngeal muscles, and pleuritic irri- tation and cough with or without effusion. T!ie following case illustrates some phases or mediastinum tumors. The patient, a merchant, age 57 years, could not recall having had any serious illness until within the past six months, at which time the present trouble began. He has had to get up once or twice each night for the past four or five years to urinate. Six months ago he weighed 235 pounds, which was about his average weight ; to-day * Read Iieforc tlie Western Surgical Association. Denver, December 8, 1914. " From Surger.v, Gynecology and Obstetrics, May. 1915. Page JU IV. D. HAJNliS he weighs 170 pounds. Four months ago he began to have a distressing cough, ai- tliough he could raise nothing from the lungs. He sometimes vomited during the efifort, and this was followed by marked relief. Sliortness of Ijreath had caused the patient practically to abandon his business affairs. He liad taken much medicine including iodides, without benefit. On more careful questioning the patient said he had had pain between the shoulders for a year or more. This was increased after eating or on lying down, and especially made worse by rapid walking or lifting. He could not lie on the left side. Physical examination revealed a mottled, brownish discoloration of the skin, with prominent veins: the left chest seemed to be slightly fuller than the right, the supra- clavicular glands on the left side were large and movable but not tender: there was a slight bulging at the su])rasternal notch : light pressure at this point caused an intense eougliing seizure, following which the patient was hoarse until after taking a sip of water. There was dullness over the left chest, which extended as high as the sixth interspace with the patient in a sitting posture. This dullness changed with a change in the posture of the patient. Dullness behind the sternum extended a short distance to the right and was continuous with the heart dullness on the left. The breath sounds over this area were absent and they were indistinct over the rest of the left chest below the scapula. The heart action was rapid and irregular, but no valvular disturb- ance was detected. Protracted cough and ra|iid Uiss of weight had caused my consultant to regard th,' case as one of tulicrculnsis. but the absence of fever and the fact that no rales were present, although the disorder had been going on six months, made it seem more probable that some more serious disease was causing the pain, which had been per- sistent from the beginning. The apical dullness was readily explained by the presence of the enlarged glands, and the absence of fever and local muscular spasm would rule out a high Pott's thus narrowing the probable limits of diagnosis to two conditions — aneurism or tumor. The rapidity with which emaciation had taken place (he had lost 60 pounds 'n six months) caused me to favor malignant growth in the mediastinum as the most probable ex|il.in,ition of the symptoms and physical findings. Fluid aspirated from the left plniiir.il ia\iiy was clear and the X-ray showed a distinct shadow extending from the ^upra^t.in.il ncitich downward a distance of 2>< inches and projecting beyond the The growth was removed by suliperiosteal resection of the inner end of the left I lavicle aud attached muscles. It was made up of a number of enlarged lymph-glands rather loosely held together. Little difficulty was encountered after exposing the mediastinum, as the mass was shelled out easily by means of the finger and scissors. There was very little haemorrhage at the time of operation, and save a troublesome leakage fnmi a large lymph-duct, proiiably the left jugular, the patient made a smooth recovery and lived two years after the operation, dying of some brain trouble. An autopsy was not obtained. The laboratory reported the growth as a lymph-sarcoma. Another case may also prove of interest. .\ man 55 years old presented a history similar to the foregoing and was in ex- tremis when admitted to the hospital. We attempted to remove the growth by the method outlined above, but owing to the intimate attachment of the tumor to the trachea complete removal was impossible. The growth, which sprang from the re- mains of the thymus, had permeated the entire thickness of the tracheal wall and showed vegetations on the lining surface. The tracheal rings had been destroyed bv pressure, permitting the walls to collapse to such a degree as almost to occlude the lumen. As in the preceding case herein reported, the method of attacking this growth gave a very good exposure, and we succeeded in removing part of the tumor before it became manifest that complete removal would necessitate resecting a segment of ihe trachea. The patient died within the next 12 hours, and this specimen was removed after death. The growth is a sarcoma. For our purpose we may arbitrarily divide tiiese growths into benign an(! malignant tumors, the former group including aneurism, gumina, and tuber- culosis, tlie later inchiding sarcoma and carcinoma. ( Mher morbid growths nccin- in this region, Imi the above are the inore fre(|iient varieties and ail Mifficienl for consideration in a twenty-minute paper. Pogc l',.j RAXSOHOFF MFMORIAL VULUMF Conclusions founded on observations of the natural history of these several growths will best serve us in their early recognition and differential diagnosis. Some of these growths run a much more ra])id course than others; some present marked constitutional symptoms and serious iinpair- ment of the general health long before symptoms referable to the chest manifest themselves. Recognition, therefore, of the wide difference in the general as])ect and progress of intrathoracic growths, aside from the special features which in no small measure characterize each case, becomes paramount in the diag- nosis, prognosis, and management of these growths. Malignant growths, for instance, as a rule grow much more rapidly than the benign ones, destroying life in from 12 to 18 months. A notable exception to this rule is found in lymphosarcomata springing from the posterior mediastinal glands or remains of the thymus. Such tumors may attain an enormous size and the patient live a long time, death finally resulting in consequence of metastases. Growths springing from the connective tissue in the mediastinum — sarcomata — may attain considerable size without producing symptoms, this being due to the laxity of the tissue and the ease with which enlargement may take place in all directions. To the writer's mind this is a valuable point to remember in attetnpts at localization of chest tumors. The site of the aneurism is more or less fixed, and you will recall that it is in this type of case that we encounter those enormous deformities of the chest, including bulging, erosion, and fracture of the bony cage. Extensive deformity oc- curring relatively early in the history of intrathoracic neoplasms may be induced by implication of a bronchus, which causes collapse of the corre- sponding lung and compensatory expansion of the opposite side. Derange- ments of the circulation are constant concomitants of mediastinal tumors : they are caused, not alone by external pressure upon the vessel walls, but also by the inherent tendency of sarcomata to permeate the walls of the veins, thereby inducing partial or complete occlusion and metastases. The effects are manifold, finding expression in oedema, metastases, hsemorrhagic effusions into the pleura, pulmonary and cerebral apoplexy, gangrene, and death. Although functional disorders of the heart with modified rhythm and sounds, without discernible valvular or muscular impairment, are the usual findings, cases are recorded in the literature wherein the heart has been in- volved in a similar manner to those rare cases of malignant breast in which the disease, by extending through the thoracic wall, affected the heart. Pain in some degree is usually present, but the chief complaint of th patient suf- fering of mediastinal tumor will be of his inability to get his breath; the pain, cough, and aphonia are annoying, but the dyspnoea is persistent and terrifying, filling the patient's mind with ominous forebodings, 'i'his, the most prominent of the subjective symptoms, is characterized by a wide dis- crepancy between the amount of exercise and the respiratory disturbance ; Pane I'fi ff". D. HAIXES for instance, the writer has seen a patient, the subject of a mediastinal growth, who had been sitting in perfect comfort, bring on by merely walking across the room a violent spasmodic coughing seizure and serious resiiirator;; embarrassment. From what has been said il becomes apparent that no one sigti or symp- tom or hitherto described order of phenomena can be said to be [lathognc- monic of a certain intrathoracic growth. The cases vary widely, but by eliminating the ordinary forms of disea.se in a patient suffering of serious derangement of the mechanics of the chest, one is warranted in making a presumptive diagnosis of mediastinal tumor. In the differential diagnosis aneurism stands out preeminently for first consideration. The physical signs of aneurism comprise a loud murmur or splashing sound, accompanied by a purring thrill, which is imparted to the hand of the examiner when placed on the chest, and interference with arterin/ circulation, delay, feebleness, or absence of the radial, brachial, or carotid pulse. Interference with the return flow is common to both aneurism and solid tumors, occurring nnicli earlier in the history of the latter than in the former. Retardation of the radical ])ulse on one side may be observed in cases where an aneurism is situated distal to the origin of the great vessels given off l)y the aorta. Sphygmographic tracings are of signal value in the dif- ferential, and comparative tracings should greatly aid one in definitely fixing the site of the aneurism. Symptoms dependent upon jjressure manifest themselves later in aneurism than in other growths, but, aside from this, possess no particular difference which would serve as aids in the diagnosis. The physical signs of aneurism, like those of other intrathoracic growths, will vary with the time of observa- tion ; if the subject of an aneurism presents himself at a time when there is a considerable degree of elasticity in the sac-wall and, above all, at a time when fluid contents fill the sac. the classical expansible tumor, peculiar vibra- tory thrill, and loud tumultuous sounds render diagnosis easy ; cjuite different, however, are the signs after layer upon layer of clots are deposited upon the inner surface of the sac. Instead of a resilient sac we now have to deal with a thick, rigid wall which limits the production of sounds, interferes with their transmission to the ear of the examiner, and presents the char- acteristics of a solid tumor. Although sarcoma is the prevailing type of malignant tumor found in the mediastinum, carcinomata are found sufficiently often to enable us to sum- marize their leading clinical features. Primary carcinoma in this region has, in the writer's experience, more frequently begun in the gullet than else- where, and the symptoms are those of a slowly but steadily increasing difli- cnlty in swallowing; solids are first discarded and in the course of a few months the patient rapidly succumbs if not relieved by surgical measures. R.IXSOIIOFF MliMORIAL VOLUME Sarcomata in their early history are painless and increase in size slowly Owing to these facts the patient does not present himself until pressure symptoms — cough, hoarseness, or dyspno?a — drive him to seek council. Rapidly growing tumors, like gummata, are painful very early in their course, and pressure symptoms, irregular pupil, aphonia, and dilated sur- face veins and serious right heart embarrassment soon follow. Growths i.; the anterior and superior mediastinum are in a measure distinguished by pressure exerted by them upon the superior cava and innominate, while in- terference with the inferior cava or azygos would suggest the presence of a tumor in the posterior mediastinum. Implication of the venous circulation, ciliomotor roots of the sympathetic, recurrent laryngeal or pneumogastric, relatively early in the history, speak for solid tumor as contrasted with aneurism, which always shows symptoms on the part of the arterial circula- tion long before venous stasis becomes manifest. Tuberculous adenitis, leading to caseation and abscess, afifect this region, and the enlarged glands must be differentiated from other growths. This condition, like gumma, is ordinarily not difficult of recognition, as in either instance we are dealing with the local expression of a disease which has almost innumerable general symptoms, a sufficient number of which are usually present preceding the central chest lesion to readily distinguish them from other conditions found in the mediastinum, h'inally, we possess val- uable therapeutic tests which will aid in the differential diagnosis of both tuberculous and luetic growths. Patients dead of sarcoma of the mediastinum are singularl\ free from metastases. Aloney, an English pathologist, posted a ntnuher of bodies in which the disease was wholly confined to the mediastinum, and the writer's experience in the dead room tends to con.firm this view. If Ibis observation proves true in any considerable proportion of the cases of sarcoma originat- ing in the mediastinum, it should encourage surgeons in their efforts to re- lieve, by operation, a condition which has hitherto been regarded as well- nigh hopeless. Numerous methods have been devised for exposing the anterior and superior mediastial sjiaces ; they include trephining, osteoplastic flap, and longitudinal division of the stenuuu ; these and other operative procedures were divised with a view to dealing with aneurisms. liardenheuer separated the muscles subperiosteally from the clavicles and manubrium, and then by dividing the clavicle and first rib on one side he wa.; able to remove a growth from the mediastinum. The writer has employed this method in two instances, and while a fair exposure of the field is ob- tained, there are certain obstacles which should be regarded before attempt- ing the operation. The chief objection lies in the liability of injury to the l)leura. Damage done to the circulation in the course of the o[)eration ren- ders the field more suscei)lilile lo infection, and lastly the o|)rraliiin i^ tech- nically difficult. Page /.(S IV. I). HAIXIIS The operation devised by Milton for ejiposing the mediastinum is less complicated and free from these objections, and it gives a more satisfactory exposure of the field for operation. He divided the sternum longitudinally throughout its entire length in order to remove a foreign body from ih;' riglit bronchus, which he successfully accomplished. .American surgeons, notably Curtis, with a view to avoiding injury fo the pleura have modified the operation by limiting the division to the manubrium, at which poiiU the pleura is widely separated. As modified the procedure consists of an incision which is carried from the larynx downward in the midline to a point opposite the third interspace The sternohyoid and the sternomastoi muscles are detached subperiosteally and are well retracted while the manubrium is being divided longitudinally. In sawing through the bone the saw should discontinue on reaching th.e periosteum covering the posterior surface and a chisel should be inserted to pry the severed margins apart. This enables one to divide the periosteum safely under the guidance of the eye. Mayo's blunt pointed scissors are well adapted for dividing the jjeri- osteum. The margins of the divided bone may be retracted two or two and one-half inches, permitting the free introduction of instruments and fingers. In doing the operation the chief structures to be avoided are the pleura and the internal mammary or its branches. Division of the latter will cause haemorrhage, which is difficult to control. The writer's experience with the Milton operation has been limited to the cadaver. However, the exposure obtained Ijy this method will permit one to ligale the innominate, carotid, or subclavian and deal with operable neo- plasms in this region. RKl'l'.RKNCES I>.%CuSTA. Pliysical lliagnosis. fl.lNT. Practice of Medicine. Cahoi. Uifferenlial Hiagnosis. A STRIKING ELE\'ATir)>; OF THE TEMPERATURE OF THE HAND AND FOREARM FOLLOWING THE EXCISION OF A SUBCLAMAN ANEURISM AND LIGATIONS OF THE LEFT SIT.CLAMAN AND AXILLARY ARTERIES.* By \\'IT.I.IAM S. HaLSTED In a series of signally interesting papers Professor Rene Leriche calls attention to the value of what he terms periarterial sympathectomv in the treatment of various neuralgias, local ischemias, reflex contractures of the Babinski-Froment type, and other afifections. Fostered in the traditions of the schools of IMagendie, Claude Bernard, and Brown Sequard, it wa.s in the happy order of things that it should fall to the lot of a surgeon of Lyon to turn to therapeutic account a discovery of the greatest of the founders of experimental medicine. A devoted disciple of Jaboulay, Leriche credits this talented surgeon, his "master," with the suggestion which led to the novel and important researches made by him during the years of the war. My interest in Leriche's work has been reawakened by an observation made only a few weeks ago in the Surgical Clinic of The Johns Hopkins University. In 1918 I ligated the left subclavian and carotid arteries near their origin from the aorta for the cure of a huge subclavian aneurism (Figs. 1 and 2). For a year the aneurism decreased steadily in size (Figs. 3, 4, 5 and 6). Then for a year we lost track of the patient. About two months ago we succeeded in tracing him, and persuaded him to let us excise the aneurism, which in the period of non-observation had developed a faint pulsation and become slightly larger (Fig. 7). About four hours after this operation, at which the aneurism was excised and the subclavian and axillary arteries ligated, it was noticed that the left hand and forearm, which for two years had been strikingly cold, had become abnormally warm — appreciably warmer than the corresponding limb. Unfortunately, our surface thermom- eter had been broken and we were unable to obtain another. About five weeks after the operation the hand and forearm became cold again — at first in small areas — remaining cold for only a day or two. To-day (June 28) the 69th since the operation, the back of the left hand is quite cold, whereas the left palm is about as warm as the right. The temperature of the hand and forearm has varied from day to day and from hour to hour; certain small, quite well-defined areas have remained uni- formly cool; otherwise, the hand and forearm have maintained their normal warmth. SuR. No. 46179. .Mexander Miller. Xegro, ,-et 29. .-Xtlmittcd to The lohns Hopkins Hospital .Npril 22, 1918; discharged .August 12, 1918. The patient states that he has always been perfectly well. In April, 1917, he noticed a swelling about the size of an egg above the left clavicle. .Mmost simultane- ously with the recognition of the swelling, pain and numbness in the upper extremity were observel. The growth of the tumor was gradual until about .March, 1918; since then it has been very rapid. For the past two weeks the liml) has l)een totally par- alyzed. The patient recalls that until Christmas, 1917, lie could still raise his arm a little. • From The Jr.hn« Hopkins Hospital Hiillelii., July, I'J2o'. WILLIAM S. HALSTED The J, •hut Hophiiis Hospital Bulletin. July. IQ.'O Fig 1 — Aneurism of the left sub- clavian artei-\, Alexander Miller. April '22, 1918. Alexander xMiller, Aim! 22, 11)18. Fig. 3.— Alexander Miller, 109 days after li,c:ation of the subclavian artery nuear its origin. Fu,. 4.— Alexander Miller, 109 days after the ligation. RAXSOHOFf MEMORIAL rOLL'MH The Johns Hopkins Hosfilal Bulletin, July, igjo Fu. .") — Alexander Miller, 10 months Fi after the ligation. Alexander Miller, In months after the ligation. Fig. 7.— Alexander Miller, 2 year.'; after the ligation of the subclavian, and 2 weeks before the excision of tlie aneurism. Fic. 8.— Alexander Miller. 1 month after excision of tlie aneurism. WILLIAM S. HALSTED About four years liefore admission the patient was shot just above the left clavicle. The wound healed promptly. The bullet was not removed and has given him no indication of its presence. Examination. — The patient is evidently suffering severe pain, and constantly sup- ports his left wrist with his right hand. The pain, he says, is most intense from the clliow-jtjint to the hand and in the left shoulder. .\ lui^e aneurism occupies the left neck from the clavicle to the ear (Figs. 1 and 2). The head is deflected and rotated to the right. The vertex of the pulsating mass is about on a plumb-line dropped to the junction of the middle and inner thirds of the clavicle. The swelling and pulsation extend on to the chest, and the whole body is jarred with each heartbeat. Posteriorly the diffuse pulsating tumefaction spreads out to a point below the spine of the scapula. The aneurism extends upward in domeshape.' a hand can be inserted between it and the face down to the angle of the lower jaw. The whole shoulder girdle appears to be raised away from the chest wall, the acromio- clavicular articulation being apparently disrupted. The skin over the tumor is very tense and glistening. From the clavicle to about the level of the nipple the brawn.' tissues are proliably infiltrated with blood as well as inflammatory products. The trachea is displaced to the right. A systolic bruit, most distinct above the inner third of the clavicle, can be heard over the greater part of the pulsating mass. Xo thrill can be left. The left radial pulse is absent. There is slight ptosis of the left eyelid, but the pupils respond equally. Only the inner third and the acrominal tip of the clavicle can he defined with the fingers. The remainder of the bone is buried in the tumefaction. A bullet is palpable just beneath the skin to the left and below the spine of the seventh cervical vertebra. The left arm is paralyzed. The extent of the loss of motion and sensation and the degree of restoration of function will be outlined in a subsequem paper. Fluroscopk Examination. — The shadow of the aneurism extends to the lower border of the clavicle but not to the first rib. The heart seems not to be enlarged. Tlic right subclavian and carotid arteries, distinctly seen, are normal in size. Skiaijraphic Report. — Large mass in' left neck. Clavicle deeply eroded, perhaps fra.gmented. Bullet in upper dorsal region. (^/■I'Mi/io;;.— April 26, 1918. Dr. Halsted. Ligation of the left common carotid and llic left snbclavin arteries near their origin from the aorta. Kther. Wide protection of the operative field with celloidin-silk.i Transverse bow-incision just below the cervico-thoracic junction, supplemented by a vertical on'.> along the left border of the sternum (bow and plummet incision). Free exposure of manubrium and left sterno-clavicular joint. The incised tissues were oedematous, particularly so below the clavicle. The superficial vessels were abnormally large. Careful hemostasis by the fine silk transfixion method. The left two-thirds of the manubrium and the left sterno-clavicular joint were resected with the giant rongeur forceps of Esmarch, care being taken to avoid disturbing the fragments of the erodeil clavicle. The thymus gland and the left innominate vein were drawn upward and ro the right with a retractor. The trachea in the thorax as well as in the neck was displaced to the right by thf pressure of the aneurism. The left carotid, deeply situated and occupying the midline in the dust, was gently occluded with a tape ligature. This artery was thought a! first I" \>r till- lift subclavin inasmuch as, according to the erroneous testimony of an ussisiant, its .julusidn did not affect the pulse in the left temporal artery, and lessened ihe fiir(c of tile pulsation in the aneurism. To obtain access to the left subclavin artery the cartilage of the left first rib and the adjoining margain of the sternum were cut away. The arch, the anrtic isilinius ,ind descending oarta, and the left auricle of the heart were palpated with the Imutr "i the opeartor before the left subclavian, lying close to the vertebral column, was identified. With the aid of four long, narrow dissectors, two of which were manipulated by the operator and two by Dr. Mont Reid, the vessel was clearly exposed at its origin from the aorta and for several centimeters distal to this point. As it was evident that none of the various aneurism needles was suitable for the passage of a ligature at this depth, a long, narrow, bluiU dissector, slightly curved and pierced at its tip, was armed with fine silk and passed under the artery. By means of this thread and then another, linen tapes were drawn under the subclavin; both of these were tied, the second distal and close to the firs;, with force only sufficient to close completely the artery's lumen. The aneurism be- came very tense and hard immediately after the ligation, but was pulseless. The patient's condition, bad on admission and particularly so just before operation, caused us some anxiety. Traction within the thorax on the branches of the aortic arch or on the pulmonary artery affects unfavorably and eventually disastrously the IW. S. Halsted. Clinical and Experimental Contributions to the Surgery of the Thorax. RAXSOHOFF MFMORIAL J-QLUME action of the heart. The pulse, about 120 at the beginning, was 140+ and quite weaK at the termination of the operation. The wound was completely and accurately closed with interrupted sutures of tine silk. A large dead space in the mediastinum was, natu- rally, unavoidable. Healing per primam. November 9, 1918. The patient has been examined frequently since his discharge from the hospital. There has been no pulsation in the aneurism since the operation. The mass has steadily but slowly decreased in size. The patient can make slight move- ments with the left fingers, otherwise there has l)eLn no appreciable return of power or sensation in the paralyzed arm. The patient was observed frequent])- throughout the year following the operation. Slowly but steadily the inilseless tumor, during this period, diminished in size. Tlien for a year the patient. Hving out of town, was lost sight of. Exactly two years after the first operation he returned, at our solicitation, to the hospital. Now for the first time since the operation a very faint pulsation was discernible. The tumor (Fig. 7) measured in its trans- verse ( frontal ) diameter precisely the same as when last seen a year before ; the anteroposterior measurement (sagittal), however, gave an increase of about 4 cm. I decided that the aneurism should be excised, and on the 20th of April, 1920, performed the operation as follows : The skin over the tumor and a wide area about it were protected with Chme^e silk dipped in coUoidin. The incision, made through the tightly adherent silk, ran with the clavicle in its central part, curving up into the neck at its inner end, and down alon.i? the cephalic vein at its outer. Superimposed on and not attached to the greatly broadened and thickened clavicle was a sharply convex bow of bone about 9 cm. long and 6 mm. thick. This bow, recognizable in the photograph (Fig. 5), was cut awav and the clavicle bitten through with a heavy rongeur forceps at two points as close to the aneurism as possible. The cephalic \ein was divided, and the axillary artery — pulseless, reduced in size, but not empty — was ligated about at the junction of its first and second portions, through a split made in the pectoralis minor muscle ; the third portion of the subclavian artery was ligated above the clavicle ; the aneurismal sac, and the resected rib were excised in one piece. The aneurism was matted almo.it everywhere to the surrounding parts by dense connective tissue, and hence had to be carved out rather than enucleated. The identification and freeing of the roots of the brachial plexus, which were in places embedded in the wall of the sac, consumed much time. The operation was conducted in a bloodless manner until nothing remained to be done except to divide the narrow neck of the sac. The tissues of this neck proved to be thin and friable, and the patient lost a few cubic centimeters of blood through the slit in the artery — the mouth of the false sac — which was readily closed with three stitches of fine silk. The wound was closed without drainage. I am greatly indebted to Dr. Heuer and Dr. Reid for their skilful and highly competent assistance which enabled me without concern to conduct the operation to a satisfactory conclusion. At the first dressing, made on the 10th day after operation, it was noted that a little fluid had accumulated in the outer part of the wound. This was evacuated by puncture with a wooden toothpick wrapped with a few fibres of cotton dipped in pure carbolic acid. Closure of the puncture was prevented by the reapplication of the acid in the same manner on two alternate days. The introduction of a drain of any kind wc scrupulously avoid. The word "drainage tube" is in disfavor in our clinic. Shniild a UMunil become infected, tubes would be properly introduced for the purpose of disinfection, but not for drainage. Noteworthy is the fact that the patient's hand and forearm, which prior to and ever since the first operation had been markedly cold, became strik- ingly warm about four hours after the second operation and have remained warm, except in certain areas, to the [jresent time (June IS). It is improb- able that the ligation of the cephalic vein was in any part responsible for this indubitable imi^rovement in the circulation. The elevation of the tempera- ture of the liand and forearm must. I believe. l)e attributable to vasodilatation WILLIAM S. HALSTED incident to the ligations of the subclavin and axillary arteries — to the crush- ing of their nerves. This question will be discussed in the course of the con- sideration of the treatment of subclavin aneurisms in a paper about to appear in The Johns Hopkins Hospital Reports. 1 have found pleasure in translating one of the papers of Monsieur Leriche, believing that his work on periarterial sympathectomy will at this moment particularly interest surgeons who may have the opportunities and the inclination to verify his observations. While disclaiming unqualified acceptance of some of his explanations and deductions which are at variance with the teachings of physiologists we must recognize that Leriche's contribu- tions are of unusual interest and value ; they will stimulate investigation. TEUIAKTERIAL SV.MP.ATHECTO.M V AND ITS RESULTS Rene Leriche In January, 1916, and in April of the same year,2 I made known the first resuh^ which the denudation and e.xcision of the sympathetic plexuses around the arteries in causalgia and in certain trophic troubles had given me. Since then this operation has been tried in various ways. Le I'Virt, Cotte, Sencert, Lavenant, de Massaiy ami V'eau, Prat, have reported experiences with it. 1 personally ha\c perf.nin.il it ,i7 times' The moment seems to have come to imlicate briefly the essential facts wliuh th, piocc- dure has taught me. Ivlaborating the idea of Jaboulay, we must indeed de\el to uncover the artery by the classic procedure, open with the bistoury the k llulai sh, atli. separate the artery for 8 to 10 cm., get hold iif the inner sheath directly wn tlie nlsmI wall, incise it, pull one of the lips tints itia.lf wttli a l^arc'is, \r^■^. it either with the bistoury or with the grooved proJH. ,.aii|.N t< iv tiijMiiii:-' tlir ait.iy of all the cellular tissue that adheres to it. More or less rasiK a.(>itdiiiL t^. tlir , asrs, i.ne is able thus to stri]) the arterv, to decorticate a fold: thin, to I,,, s„,r, l.iil Mit,n tlii.kei- tliaii onr iiif^lit .xp.-, t. At a'eerl.ain moment one has llie mipi-rssion tli.it o,,,, ,s ^,,,im t., traf tli,' uall oi tli,. jrtnN , Imt it" .nir pro- ceeds ueiitlv and laiTtiillN. euidrd l.v tli, |ioint ,,l llir l,ist,>iii\ ,,r luol,,-. ilir ii-ceing process can be earned on witliout risk ..f iiij lit in..; llir ^^.s^l ( i|ll^ tua,. |ia\r I had the annoyance of making a small tear in tln' arte r\ : tla .M.nhiit was .Aiilioin -,iious results. In case of necessity one would fraiikl\ i-csnt the s,;oiii m oi ih, i, ,n and tie the two ends, accomplishing thus liy the same ait a r, mipk i.' s. iM|ialla . t. nir, S. am times the forceps removes only rather short cellnl.ir fra:anients. al otiui tiiiiv, oiu leiiiovca quite definite lamina', and tin- !iio\ ctneiil of freeing recalls, oii a small scale, the sub- serous decortication of an inllamrd a|i|iendi\, but oiir iu\er succeeds in removing a continuous layer; it is nerrssar> to repeat tiie attempt se\er,il times and with perse- verance to catch the sheath again, to remove thin meshes, and not to slop until one has really the feeling of having removed everything. i\!oreo\ir. one can verify what has been done by wetting the wound with a tampon soaked with \eiy warm serum: the artery takes on then a whitish appearance, looks as though made of felt, and one sees very clearly whether there remains still some cellular debris more or less detached. In the course of the cellular decortication it is necessary to be careful to expose the collateral branches and guard against tearing them. This happens sometimes; by using then a forceps ano a - c ,gut one repairs this accident without injury to the artery. In addition to the tears, which cause a spurt of pure blood, there may be o(jzing from the tearing of the vasa vasorum. II. The I'Hvsiut.ocic.M. Reaction. — The operation thus done is a physiological o|)- eration ; I mean to say by this that it is inevitably followed by a characteristic physio- logical reaction, which may be regarded as the test of the ol>eration; as there are char- Pagc KS RAXSOHOFf MHMORIAL VOLUME acteristic signs of the section of the trunk of the sympathetic in the neck, so there are characteristic signs of the section of the periarterial sympathetic nerves. If tliese are wanting, the operation has been attempted but not acconipHshed. The results of our studies of these signs Heitz and I have reported to the So- cicte de Biologic ;* they are as follows : Primary Siqn. — When one touches the sympathetic sheath, the artery contracts . it is reduced progressively in size to the point where it is not more than a third o'- even a fourth the normal size throughout the whole extent of the denuded segment. The segments on both sides maintain their normal size provided the operation has not injured them. The phenomenon is more or less rapid according to the case; certai'-. individuals appear to have more irritable sympathetic nerves than others; their arteries diminish in size at the first touch ; with some the contraction is sluggish. One cannot yet give the real reason for these variations. Furthermore, the contraction is more marked in the brachial than in the axillary and the subclavian : it is slower in the femoral than in the brachial, and less intense in the common iliac than in the femoral. In a word, the contraction is stronger in the arteries of small size than in the large- trunks This arterial contraction habitually causes the pulse to disappear, liut it does not altogether interrupt the circulation. Secondary Signs. — In the following hours the pulse is imperceptible or very feeble and the limb is colder than the other. Then little by little, at the end of three hours, six hours, and most often after twelve or fifteen hours there appears the characteristic I'hxsidlofiical reaction, the establishing of which ought to he exacted as proof that suppression of the sympathetic nerves has been properly done. This reaction is characterized )-,y an ele\atinn of the local temperature reachin.g to 2° and even 3° [centigrade], by the elevation of the arterial pressure, and by the augmentation in the amplitude of the oscillations of Pachon. M. Heitz, who with his very special competence has established these facts many times on my patients, has found that the increase in pressure could be as much as 4 cm. of mercury in compari- son with the healthy side (method of Riva Rocci) : it is a detail worthy of mention that analogous figures were noted by Claude Bernard in his investigations of the cervical sympathetic nerves. This vasodilator reaction is only temporary : the hyperthermia, the rise in pressure, and the increase in amplitude of the oscillations diminish little by little; sometimes as early as the 15th day and usually at the end of a monlli i'u "n i~ it n i more. On the other hand, in some cases in which I have performed -m ii the brachial or the subclavian artery by resecting totally the nlililer.,' ird, the eleva- tions of temperature have been more lasting than in tlu . i- - n \' In h a sympathec- tomy by denudation alone was done. This is comprehensible, for the operation is more complete — the sympathectomy being necessarily total. Classed with these observations, should he one made by M. Babinski and M. Heitz : four months after the extirpation of an axillary aneurism the hand on the side operated on was frequently warmer than that on the healthy side. This phenomenon, apparently paradoxical, is understood very well when one considers that the ablation of a sac is in reality a total sympathectomy. III. The Lessons Furnished by the OpEr.vtion. — Observation of series of opera- tions and analysis of the therapeutic results permit interesting deductions from physio- logical and pathological points of view. 1. I- row the Pliysiological Point of I'ic-a'. — Two facts become clear: the vaso- motor phenomena which Heitz and 1 have studied under the name of va,sodilator re- action permit us to isolate the paths along which certain vasoconstrictive acts are conducted and to establish their correct value. But there is, above all. this one: it seems to follow from certain observations that the voluntary muscular contraction is. in a certain sense, very dependent on the sym- |)athetic nerves. The integrity of the motor nerve and of the muscle are not sufficient to insure the proper accomplishment of the movement that is commanded. If the sympathetic nerve is affected at a distance, or if it does not act normally, the muscle becomes hard, and contracts, and the will is powerless to relax or contract it. Now in these cases sympathectomy lifts the barrier and makes possible the progressive reparation of the voluntary movements. In the case of wounded men having reflex contractions of the Bahinski-Froment type, with fingers twisted, motionless, incapable of movement, it has been sufficient to modify the vasomotor innervation to see a cer- tain degree of voluntary motion appear again the following day. This fact which M. Heitz-'' and I have confirmed several times has a rea! Des effet! Iherminue et hyptrtension locales). SLeriche and Heitz: Influence segment aileriel oblitere s ur la contra pliysiologii]ues de la sympathectomie periphcrique (r ". R. de la Soc. de Riol.. 20 Janvier. 1917. [le la sympathectomie periarterielle on de la resectio; ■lion volontaire des muscles. Societete de Riologie. 17 1 WILLIAM S. HALSTED physiological bearing. What we now know of muscle inner\ation in man docs not lead us to suppose that it is a matter of a directly muscular actii>n. It appears. ur*il we have made further inquir\. thai the \ a^' mii iti.i iihim iimii.i .il.nc are concerned in it, and a fact which would tend i.i pr^v. tins is ili.ii ili. utiiiii .ii ni^.tdity coincides with the appearance of the p. isi Mip.r. uu c \ .isodilaP ii- ir,Hii..ii i tlial is Ici say. the warming up of the muscle, its new rirciilut.iry system i, and ImH.iws the course of it. Sympatlicctnmy. furthcrmnre, would appear to establish the fact that the sympa- thetic ncr\e is, in man, the excildsecretory nerve of the sweat glands: 1 have seen l)ri..fuse sweatinL; ..f the hand disappear after svmpathcctomv. The nerve prn1)abl\ also inllu.nces the i;r.,wth ..f the nads and the tr,.phirilv ..I'lhc skin, s.nce In.phi.- phen.inu-.i.a drsappear rapi the predominating feature has not the mark of ischemia. I do not mean to say that the circulatory suppression caused by the arterial lesion does not play any part, that would be absurd : what I would say is that something more is involved. But these cases are too rare in general surgical practice for me to follow the analysis alone. (f) The role of the symfalbctic iu the I'rodiictioit of heel sloiiglis in the course of mednUary lesions. In one patient who had had flabby incomplete paralysis of the lower limbs with absence of reflexes, and incontinence of urine, there were two sloughs, one on the heel, the other on the little toe. They resisted all treatment. Three months after the wound had been received, a femoral sympathectomy was done. Three days later the ulceration of the toe was dry and cicatrized: that of the heel, which was as large as a small palm of the hand, diminished in size and was covered with active granulations. In thirty-five days it was completely cicatrized. 3. From the Therapeutic Point of View. — I have tried sympathectomy in a great variety of cases, and it is rather difficult for me to analyse the results, because there were often complex situations to be dealt with. Schematically, 1 have tried to influ- ence the element of pain, the element of reflex contraction with vasomotor dis- turbances, and the trophic element. In all the cases I have had failures and disap- pointments. I have done sympathectomy eleven times for phenomena of pain : ^once the vaso- dilator reaction failed. This operation was badly done and I elimina'te it. For the ten others, six times there were true causalgias, and three times phenomena of pain more or less intense. For cau.mlgia I operated four times on the upper extremity, twice on the lower limb. The four cases in the upper extremity resulted as follows : One complete failure (patient operated on in the service of M. Gosset"). two excellent results f com- plete suppression of the pains, total transformation of the patients') with final cure, now dating back 19 and 16 months. These two patients have been discharged, and are earning their living exclusive!)' by their own work. In a fourth case, which was very serious, I had found the brachial artery ob- literated. I had not at the time thought that there would be any advantage in re- .secting the obliterated segment. I performed then a sympathecomy by denudation The patient w'as much improved : he who for months had been confined to his bed with a wet cloth on his hand, apprehensive, indifferent to everything except his pain, got up and submitted to the same regime as his comrades : but some pains persisted. Tn order to improve these I again took the patient under my care and resected the ob- literated arterial segment, whereupon the persisting disturbances almost completely vanished : this result promises to be permanent." In the lower limb I did one femoral sympathectomy, with appreciable ameliora- tion. At a second operation I resected the sciatic artery and the artery of the sciatic nerve, with manifest result, but the cure has not been complete. The patient, who has been followed for six months, is entirely relieved at certain times, but has suffered much at others in damp weather. His general condition is transformed. For those who know the lamentable condition of degeneration of these patients caused by their martyrdom of pain, the words "great amelioration" have a real significance. This expression should not be taken as a euphemism masking a failure. In another case I did a common iliac sympathectomy, which resulted in great improvement [grande amelioration! with complete transformation of the general con- dition. The patient has suffered at certain times, but his days of respite have been greater in number than his days of pain. This is also, to my thinking, a success worth trying for. 6. Tn one of the last Bu'lnins of the Socu'lc de Chirureie a very intL-resliiiK observation by M. Le Temtpl is reported, which shows well the rnle of the sympathetic in the paretic syndrome fol- lowing an obliteration of the brachial. WILLIAM S. HALSTED For all "causalgiqiies" the question is complex in other ways: these patients have a psychology of their own ; it is necessary to isolate them somewhat and to exercise over them a little authority if we desire to cure them. Besides, they are extremely sensitive to atmospheric changes, and it seems as if their whole vasomotor system were out of equilibrium. One local operation could not pretend to set all this right at once, and these patients should not be regarded exactly as others. I have operated four times for fhenomena of pain accomfanying vicrvc lesions or arterial obliterations. I had three excellent results and one complete failure. To sum up, in the treatment of the phenomena of pain, sympathectomy cures entirely certain patients, acts very favorably in the majority of cases, but does not suc- ceed always or always give an absolutely perfect result. Five sympathectomies for trof'hic ulcerations, with or without phlycten;e in the neighborhood, gave success five times- I have operated three times for large bluish oedemas of the limbs, with one com- plete success ; one great improvement, followed at the end of several months by com- plete cure: one incomplete result with partial return (in the lower limb), but on the whole, amelioration. For reflex disturbances, eighteen sympathectomies among the patients examined heretofore (except two) either by M. Babinski, or by his assistants M. Froment and M. Heitz, and all followed up by M. Heitz. have resulted as follows:'' Three cures, practically complete, traced for several months, with disappearance of the vasomotor disturbances and of the contraction ; Ten ameliorations more or less considerable, some of which were almost cures: Two ameliorations followed by incomplete return in patients who had not received any post-operative treatment. In the two cases the lasting benefit has been real : One case in which the operation, after failure of all other treatments, has been followed by the execution of voluntary movements: :iKm, thanks to trciitment followed regularly under the direction of M. Heitz, motilit\ i^ utiii iiiiil; hitli- by little: Two complete failures. In these two patients tlnre had Ih-iii alter operation a beginning return of voluntary motility, but the therapeutic result has been practically In all the patients who have been really benefited by the operation (16) the vaso- dilator reaction has been followed by a diminution of the contraction and by a reap- pearance more or less complete of the voluntary movements. In some cases the result has been surprising : from the day following operation the patients were able to make movements which had been impossible for months. But at the end of two or three weeks, as the vasodilator reaction subsided, the contraction shows signs of beginning anew and the movements diminish in amplitude. Observing this, we thought, with M. Heitz, that the maintenance of heat in the member operated upon was indicated. For this purpose M. Heitz has made my patients take baths of paraffine at 60° for about one half hour. By associating with this treatment massage and re-education Heitz has obtained very interesting results, which permit us to speak, in certain cases, of true cure. Briefly then, in the grave forms of the syndroine of Babinski-h'roment sympa- thectomy by itself does not suffice. But without it, the treatment usually applied soon ceases to influence the condition, and the result becomes stabilized : the operation, like so many other operations upon the nervous system, leaves room for and facilitates re- education, and gives to it its eflicacy. It is only one phase of the treatment, but it is a very rewarding phase. 1 insist on this point so that we shall not expose ourselves to failures ail the more bitter when the operation at the outset promised to yield a bril- liant result. -\nd 1 recall what Heitz has recently written :* it is the mixed method (operation on the sympathetic followed by the treatment indicated above) which has given in the scr\icc of M. Babinski the best results. /■'())• thr paralyses connected unth vascular obliterations, associated or not with nerve lesions, sympathectomies have improved the criii.lition without giving, except in one case, a true functional result. In such case the s\ iii|iailu< lomy sliould lie done to modify the vascularization of the paralyzed segment, to clmk the libroiis regression of the muscles. It cannot constitute of itself a sufiicient Ireatnunt, but it has appeared to me to be interesting and useful. The future will determine its indicalion. 7. 'J'lie observations will lie piiltHslu.l m twlcn.so in the .^ul^u^l iuuiiIm i :renc aft. Ihe popliteal vessels. The operation was followed by complete d.sappearani the hue of the violet-colored spots which covered the limb. For 36 hours result, but none appeared, and I had to amputate the thigh. THE PATHOLOGY OF CHROMIDROSIS.* M. L. HEIDINGSFlil-D. Ph. P... M. D. Cincinnati. The name chroniidrosis imphcs an anomalous secretion from the sudori- ferous or sweat glands characterized by colored perspiration. Its occurrence is exceedingly infrequent ; Foot.' in a careful review of the lierature dating from 1709 to 1868, has been able to enumerate but 38 cases, to many of which a doubtful character must necessarily be attributed. Fowie's- careful historical review, 1709-1891, does not add many well-defined cases, and surprisingly few have been reported in the literature of recent years. Its marked infrequency can be best a])preciated by referring to the \'an Har- lingen's-'' statement, that "it is so rare as to be a curosity rather than a dis- ease." Those who have written on the subject, almost without exception, are of one accord as to nature, and attribute to the condition a disorder, functional or otherwise, of the sweat glands. This is especially evident in all the text- books of skin diseases, where the sulijects are not alphabetically arranged and follow some system of classification ( Hyde.* Hardaway.'' Morrow," Kaposi,' Duhring,^ Joseph," Stehvagou,'° Shoemaker,'^ Schamberg,'^ Fox,'^ Gottheil,'* etc.) ; in these the affection is invariable classed with th;; anomalies of glandular secretion, namely, the sudoriferous glands, and i.-; grouped with hyperidrosis, anidrosis, bromidrosis, uridrosis, hematidrosis, etc. In those which follow an alphabetic arrangement an anomaly of secretion is, as a rule, directly attributed, or indirectly implied (Jackson,'' \'an Harlingen,'" etc.), apparently a few (Lesser,'" Mracek," Bulkely,'" Neumann,^'' etc.), studiously refrain from committing themselves. It is surprising that some of the earliest observers ( Nelligan, Wilson and Gin- trac) have attributed the condition to a stearrhea, and Turenne to a metas- tasis of the eye pigment, facts which seem not so remarkable when we con - sider that the early investigators were very keen obser\ers and relied alinost exclusively on their powers of personal observation. The color of the secretion varies with different cases, green, blue, purple, black, brown, yellow, red and intennediate shades. Black is the most common, occurring is one-half the cases reported by Foot. Cases character- ized by red pigmentation are generally associated with a reddish incrusta- tion of the adjacent (usually axillary) hairs, the bacteriologic examinatioii of which reveals the condition to be due to a Zooglea (Bacillus prodiyiosus) , which grows in rose-red colonies and often gives a history of direct con- tagion. These cases cannot be properly classed with the so-called chromidro- sis, but belong, by nature, with greater propriety to the class of so-called vegetable parasitic afTections of the skin. • Read at the Fifty tlii rd Annua 1 Mi CL-lii ,,f the American 1 .Medical .\s )f Cutaneou; ; Medi icine and Surgery, and ^:" raved for publicalii Dn by tlie E> ,V. T. Corle ■tt, L. Dune, an Bulkley i ind L. Bauni. ♦ From the J^ of 1 M edi sociation. December 1 RAXSOHOFF MFMORIAL VOLUME In my own clinical and private practice I have noted eight cases of this so-called red chromidrosis during the past two years, in most of which there was not only a reddish discoloration of the incrusted hairs, but also distinct reddish discoloration of the superimposed garments. If this class of cases is included, chromidrosis is by no means a rare affection, and it probably falls to the lot of nearly every close observer to note these cases from time to time. At present I have, among others, two patients under observation with this form of affection, an uncle and nephew, the latter of whom is a practicing physician, who has taken up his residence with his uncle during the past four years. The physician states that his infection is of five years' duration, and that his mother, with whom he then resided, is similarly af- fected, and has had her affection for almost the same length of time. His uncle acquired the affection almost four years ago. and more recently hi.s daughter has also been infected. The axillse in all the cases have been involved, and all the cases show tiie red discoloration to a marked extent. From these and other cases in the literature it is clearly evident that these forms of reddish discoloration are readily contagious, and owe their cause to a local infection, entering from without. Their parasitic nature is further evidenced by the fact that some of my cases of so-called red chromidrosis have readily yielded to a few applications of \\ilkinson oint- ment. Though nearly all who have reported cases of red chromidrosis have attributed the cause to a parasite, dift'erent authorities vary as to its true nature. A few (Labrares et Cabannes'^j strongly deny its bacteriologic nature ; Temple-^ attributes it to the ingestion of potassium iodid ; Stott,-^ to toruL-e, which grow in rose-bed colonies on potato culture at 38 C, and deep red at O C ; Fowie'* ascribes the cause to theBacillius prodiglosus ; Babesiu^"' to a form of Zooglea, and Hartzell-" to a fungus bearing a resemblance to the Micrococcus tetragenus. This marged diversity of opinion induced me to make culture experiments on potato, gelatin, agar. etc. Potato cultures served the best, and though contaminations were very common, involving diflferent forms of sarcina, staphylococci and bacilli, deep brick-red colonies could be isolated in most instances, whose microscopic appearance was .1 Micrococcus tetragenus. Inoculation experiments were not attempted. Let us now digress from the so-called cases of red chromidrosis and resume with the more well-defined cases, in which, according to Foot.-' 34 out of 38 were women, 19 out of 29 were unmarried, age varied from 5 t ) 57 years, average being 22 years ; the face, particularly the eyelids, is most commonly involved and uterine disturbance and hysteria are frequently as- sociated. In nearly all the cases the attack comes on suddenly without ap- parent cause, and persists usually for a few years in intermittent form. The case which I wish to report occurred in H. O., a brunette, a native of Germany, aged 53, a merchant of intelligence, good social standing, who had been married for fifteen years and is the father of one child. His general health has been excellent; in 1898 he suffered with an attack of hepatic colic, which was followed by jaundice, and ihe following year, under severe medication, involving salivation, he passed a large Patic lii> 71/. L. IIEIDINGSPliLD number of gallstones. In a short time he regained his customary good health, which has been uniformly good since 1900. In 1901, he noted for the first time that the linen of his right forearm became discolored. The discoloration was a yellowish-brown and permanent in character, so that it could not be removed in the process of laundering. The discoloration was rapid and extensive, so that in two days' time a new cuff or a new shirt sleeve was very perceptibly and indelibly discolored. The coat sleeve lining ^l& . 1. Hyperkeratosis in o P and P; in corium, P (VVinckel, oc. 2, obj. 5.) shared in the discoloration to such an extent that its renewal, for cosmetic reasons, every two months, became a necessity. The patient was able to take note of no other subjective or objective symptoms of any character whatever. The condition has per- sisted continuously for the past two years. Perspiration has not been excessive and to the patient's knowledge but slight. When patient presented himself for examination, for the first time on March 5, 1902, the skin over the affected wrist was apparently normal ; there was no evidence of any intlammaticdi, and no disturbance of innervation. Compared with the skin else- where on the li.idy and with the opposite wrist, there was a very slight, evenly-diffused :/ Fig. 2. Two circumscribed accumulalicni (VVinckel, 1, obj. ,1 ium, P and P. Pant- /'.'..■ RAXSOIIOPF MEMORIAL VOLUME pigmentation, as if the affected area had been hghtly bathed witli tincture of opium. !t remained unchanged when scrubbed with pledgets of cotton dipped in water, soap, alcohol and ether and the pledgets themselves took on no discoloration. Pledgets dipped in chloroform removed the discoloration rapidly and left the areas thus treated much \v]i'!< r ' ■ -'Id I I i; ill llic surrounding area. K-N.ir . ' ■ r , , .l:(,wed reaction faintly acid, no alliumin, nn sugar, no formed' ^- ;t> 1020 and no indican. L'.lood examination by Dr. .\lf red Friedlaii'!< 1 :; .. i ii ^ -,ir,.'ii..n from the normal. An e.xaminatiun of the secretion, which was collected on pure white linen, revealed it to be insoluble in the ordinary solvents, ether, alcohol, water, glycerin, xylol, etc., and readily soluble in chloroform, imparting to the latter a yellovvish-brown color. Hydrogen dioxid exerts no bleaching action on the yellow color. When evaporated on glass slides it formed a smooth yellowish substance, which under the microscope revealed a semi-crystalline appearance, due no doubt to the admixture of old. dried-up epithelialcells and other detritus ( Fig. 5 ) ; when previously filtered, the microscopic appearance is amorphous and structureless : when the chloroform is completely evapor- ated, the deposit retains a resinous character, readily taking the impression of the finger and showing with minuteness the folds and furrows of the skin, or can readily be etched by means of a needle. Fig 3. Circumscribed ;u . 1'. witliin the rete malpighi The eliminated substance is unaffected by acids (nitric, hydrocliluric. sulpluiric. carbolic), and fails to give the characteristic reactions for indol, indican and liile pig- ments. The negative character of these reactions and the absence of indican in the urine is sufficient evidence, I believe, to dissociate this affection from renal and hepatic predisposing influences, notwithstanding strong opinions to the contrary (Labrare,s,2S Hofmann^S) and the pre-existing liver disorder in this particular case. On March 8, a small piece of skin was removed from the anterior surface of the wrist, near the ulnar border, central to the area of greatest discoloration, for the pur- pose of microscopic examination. It was thoroughly washed for one-half hour in running water and hardened in successive alcohol ; the use of formalin, Miiller's fluid, etc., was purposely avoided, in order not to induce discoloration, or to conserve the mask pigmentary changes. The preparation was imbedded in ■ 1 in successive serials, and examined partially unstained and Mied with polychrome-methylene-blue, eosin. hemato.xylin-eosin. 1, \'an (liessen. thionin. orcein, etc. The unstained specimens lined with polychrome-methylene-blue (.Unna). decolorized with 111 the most interesting changes. ras first i-eim-rc(l in the microscopic appearance of tlic y are found to he normal, sliowing; no cystic dilation, n' blood, celloidi and thereb\ hemai' and th glyceri n ctluT, sf,,,- .M' V interest sweat glands : th M. L. HEIDINGSFELD pigmentary infiltration, no discoloration and no inflammatory changes. In other words, no pathologic alterations, no structural variation from the nor- mal can be detected in these elements, which, in any manner or form can induce, or result from, a so-called chromidrosis or colored sweating. (Fig. 5.) This finding accords with what would l)e naturally inferred from the nature of the pigmented elimination, the latter being thoroughly insoluable in water, could scarcely be eliminated by a secretion essentially watery ii character. The general appearance and structure of the skin is almost normal. The epidermis, cerium and subcutaneous connective tissue are normal in their general structure and contour. The stratum corneum, rete mucosum, papilla;, capillaries, ducts of the sudoriferous glands, show no marked variations from the normal. A marked hyperkeratosis is present aniund the opening of the Fig. 4. Circumscribed accumulation of pigment, in curium, with a central cavernous space. (Winckel, oc. 1. obj. .i.) hair follicles, and the adjacent stratum corneum is thickened to two or three times the natural size. (Fig. 1. Associated is the entire absence of sebace- ous glands. Although hair and their follicles were abundantly present, and innumerable specimens were carefully examined, not the vestige of a sebaceous gland was discovered in any of the specimens. Elastic fibers, though abundantly present, showed no marked variation from the normal. Examination with the higher powers of the microscope readily show the presence of small, roundish yellowish particles, which for the most part are located in definite areas of the specimens. They can be most easily detected in unstained preparations, particularly those which have been pre- viously bleached with hydrogen dioxid, or specimens which have been verv faintly stained with polychrome methylene blue, and decolorized with glyc- erin ether. Many are located in external lasers of the stratum corneum. exclusively in and around the hair follicles, and particularly those areas RAXSOHOPF MEMORIAL VOLUM E which show the above-mentioned liyperkeratosis. The greater quantity is distributed to the lower layers of the epidermis of those areas, where the pigmented bodies are accumulated to form compact masses, occasionally show^ing a central cavity and often distinctly walled off from the surround- ing tissues. (Figs. 2, 3 and 4.) The lower layer of columnar or germinal cells of the epidermis of this region show marked pigmentation, pigment of the same form and color, as described above, and contrasting strongly with the pale germinal cells situated elsewhere along the epidermis. In and around the papilke, extending for some distance into the corium. and in close proximity to the hair follicles, adjacent tu the pigmented germinal cells of the epidermis, are numerous small pigmented bodies, for the most part rolmdish, but often irregular in outline and retaining the same general analog)' to the above-mentioned pigmented bodies. The latter cells t •%: Fig. 5. Showing normal condition of the .sudoriferous glands. (Winckel, oe. 2, obj. 5.) have an analogy to the s(j-called chrcmopliore cells, which are believed to bear the pigment of normal cells from its origin in the cutis to the epidermal cells. They retain the same localization, and apparently perform the same function, the distribution of pigment from the cutis to the epidermis. They differ, however, materially in certain characteristics. They are smaller and more roundish in outline, and show no long proto-plasmic processes, so- called pseudopodia. by reason of which these cells were for a time supposed to possess ameboid movements and carry the pigment from its point ol emanation to the epidermis. Ballowitz'"' has been able to demonstrate that the nerve endings penetrate these cells and envelope them thickly with dichotomous branches, thereby precluding their movement. He had also been able to demonstrate in the scales of fresh herring that the apparent change of form is due to the transportation of the pigment (which in the chromophores is finely granular) within the cells. The chromophores there- M. L. HEIDINGSFELD fore probably serve as mere "stepping slones" or fixed carriers for the pig- ment in its course from the deeper structures to the surface. The pigmented bodies in chromidrosis differ from the chromophores of ordinary pigmenta- tion, in that their contents are not finely granular, but homogeneous and amorphous, and that they do not decolorize with hydrogen dioxid. I was unable to determine to my personal satisfaction the ultimate source of the jjigment in chromidrosis. That its source is from some point in the cutis is readily apparent from the examination of the specimens, but whether it springs from lymph or blood vessels, from pre-existing cell tissue, or what not, will be equally if not more difficult to determine, I be- lieve, than the present unknown source of the pigment of the cutis. Its ap- parently free dissenn'nation in the epidermis, tissue preeminently vascularized Fig. 6. Concretion attaclied li, „ ..„ „... „ .. (Oc. 1, obj. .3, Winckel.) f red cliromidrosis. by lymph, leads me to concur with Moritz Cohn,^' that the pigment is derived from the lymph s])aces of the cutis. I regret that I have been unable to discover in my investigations into the literature any report on the histologic changes in any of the cases thus fai recorded, inasmuch as a comparison would have been of great interest and confirmation of great value. No mention of chromidrosis is made in Unna's^- "Histopathologie der Haut," a work that is very comprehensive as regards the pathology of the skin and replete in all its detail. One case is hardly sufficient, especially in a disease w^iich shows so many variations, to serve as a standard for all, but its marked infrequency precludes the reports of accumulated cases. With the hope that a spectroscopic examination may have been able to shed more light on the nature of the eliminated pigment, a chloroform solu- tion was sent to Mr. C. P. Fennel, who has kindly reported that absorption RAXSOHOFF MFMORIAL J-QLUME bands were not present, and hence it was not a product of hemoglobin or oxyhemoglobin. Sodium bands, somewhat expanded, were present, togethci' with two faint, narrow interposed lines, which could not be read with any degree of satisfaction. A careful chemical analysis has not been attempted, but for reasons above stated I do not concur that it is derived from indigf) or indican, bile or hemoglobin. I belie\e. for the present, it can be classed with due propriety with the large class of pigments of the body, the nature of a large number of which is, as yet, so little known and imperfectly under- stood. I am unable to attribute to my case any direct or predisposing cause. He is of a temperate, phlegmatic disposition, quiet, unobtrusive in nature and had noted the affection over a year before he became sufficiently interested to bring it to the attention of a physician. Similation has been carefully ruled out by applying a coating of zinc gelatin to the affected area, after a Fig. 7. Structural appearance of the concrctiuii attached to a hair, taken from a case of red chromidrosis. (Oil immersian 1/12, oc. 4. \\inckel. i previous application of chloroform, although there were little grounds for en- tertaining any suspicions. He is not addicted to drugs (Temple^'), vocation (Dyer^*) and trauma (Geschelin^^) exerted no predisposing influence, and he is not neurotic (Fowie,^'^ Foot^'). paretic or epileptic (Delthir-''). A case of simulation came to my notice in June, 1900, Miss R, F.. aged 22, from \'an \\'ert, Ohio. Consulted in regard to a reddish discoloration of the left palm and forearm, associated with shred-like desquamation of two years' duration. The case elicited much local attention and the diagnosis- of erysipelas and a suggestion of ainputation induced the parents to seek special advice. Red chromidrosis or simulation promptly suggested itself, and a two weeks' stay in the hospital with a plaster-of-paris bandage cleared up the condition and confirmed the latter diagnosis. A confes.sion from the hysterical young woman then revealed that she had been in the habit of Page ir.S M. L. HnlDINGSFELD applying crude carbolic acid locally and tinting the member with artificial rose petals dipped in water. I have been unable to carry out any prolonged line of investigation in regard to treatement. It is somewhat difficult to suggest proper curative agents, and the same futility as regards treatment no doubt presents itself in this disease as in chloasma, vitiligo and other pigmentary disturbances. I have found that sponging the afi'ected surface locally with chloroform is an excellent palliative measure and prevents the excessive staining so disagree- able and annoying to the patient. To recapitulate, chromidrosis is not, as its name implies, an anomaly of sudoriferous secretion. Judging from the limited numlier of cases in the literature, and as a matter of common observation, it is an exceedingly rare aflfection as regards forms characterized by yellow and brown, and probablv black, blue, green and intermediate shades of discoloration. Red chromidrosis is an entirely different and by no means an infrequent type of affection, with an extraneous cause, probably some form of erythro-micrococcus-tetragenus infection from individual to individual, and yielding to antiparasitic reme- dies. In the light of this investigation the pigmented elimination, in the yel lowish-brown forms at least, is insoluble in water, alcohol, ether, etc., is readily soluble in chloroform, stains linen indelibly, shows no reaction when treated with ordinary reagents, and is amorphous, homogeneous and resinous in character. Pathologic examination reveals the sudoriferous glands of the affected area to be normal, sebaceous glands absent, a hyperkeratosis around the openings of hair follicles and pigment accumulations near the hair fol- licles, in the stratum corneum, lower layers of the rete, and the adjacent cutis. The iiigment is grouped in cell-like masses, is not finely granular and does not bleach with hydrogen dioxid like chromophores. SiJectroscopic ex- amination of the eliminated pigment reveals no absorption bands and hence it is not a derivative of oxyhemoglobin. In view of the pathologic findings, the absence of sebaceous glands, the normal condition of the sudoriferous glands, cases of so-called chromidrosis ( excluding red forms ) are anomalies of pigmentation and not glandular secretion, IiIBL10GR.\PHY. 1. root, Ailhui W.: imblin Quart. Review. 18(,y. 3. \'an Harlingen: Handbook- of SlFf MEMORIAL rOLUME In conclusion, we wish to make a plea for the early recognition and prompt surgical treatment of the cases of increased intracranial pressure, which, if taken in time, may occasionally be entirely cured or at least their headaches and vomiting may be arrested, their vision saved, often a perverted mental condition cleared up, and their last days prolonged and spent in com- ]>arative comfort. We have no doubt that there have been patients in some of our institutions for the care of mental diseases that should ha\e had the services of a surgeon. One of the large continental clinics makes a report of 100 brain cases that were operated upon. These are divisable into groups. There were 43 cases of suspected cerebral tumor, in 32 of which the diagnosis was correct. For cerebellar growth there were 22 operations, 11 of which confirmed the diag nosis. The remainder consisted of pontine tumors (12 cases), pituitary tumors (13 cases), decompression operations (10 cases). The iiroportion of incorrect to correct diagnosis in cerebral (1 in 4). and in cerebellar tumors ( 1 in 2) is very instructive. Of the 32 cases where a tumor of the cerebrum was found, 9 died of operation, and 12 were alive at periods \arying from live years to four months. Of 11 cases of cerebellar tumor, five died of operation, but only one liatient was alive at the end of two years. Of the 12 i)online tumors only four survived the operation and these were alive for periods from two and one-half to one year afterward. (Von Eiselberg's Clinic.) Due credit has been given for quotations from the literature. HOSPITALS— HISTORY OF THEIR DEVELOPMENT.* By Christian R. Holmks, M. D., F. A. C. S. Tlie origin of hospital goes back so far into the dim past that no data is available to indicate when they were first established ; but history tells us that in the eleventh century B. C. there was a college of physicians in Egypt in receipt of public pay, and regulated by law as to the nature and extent of their practice. This college belonged to the sacerdotal caste, and women were also permitted to practice medicine there. According to Pliny, as the physicians were paid officers of the State, they were required to treat the poor gratuitously. These physicians were not, however, likely to attend the sick in their own homes, or at their private consulting-rooms, except in extreme cases; and so it is presumed that, as at Athens, so in Egypt, there were official houses to which the poor went at certain times, and which cor- respond to the out-patient departments of our hospitals, or, better still, to our dispensaries. It is further on record that Egyptian physicians, though paid by the State, were allowed to receive fees from private patients. At Athens there were, in the fifth century B. C, physicians elected and paid by the citizens ; also, according to Pindarus, dispensaries in which the physicians received their patients ; and there were at least two hosiiitals attached to the Temple of .Tlsculapius. In the time of Plato some of the Athenian physicians were elected by the people and paid by the treasury. Socrates speaks of one desiring to obtain a medical appointment from the government, and there was a technical term applied especially to physicians who had a public salary. These State physicians, after election, appear to have appointed slave-doctors under them to attend the poor, while they themselves attended to the rich, and. either by their own eloquence or by that of some friendly rhetorician, persuaded the patients to drink the medi- cine, or submit to the knife or the hot iron. The slave-doctors, on the other hand, had no such scruples, but ran about from one patient to another, and dosed them as they thought proper, or "waited for them in their dispens- aries." This passage shows that there were at Athens, in the fifth cen- tury B. C, dispensaries to which the sick poor repaired for treatment of their diseases by the slave-doctors, who were appointed and paid by the State physicians to look after ailments of the poor. These dispensaries varied in number, according to the prevalence of diseases. In Hippocrates himself — "The Father of Medicine," as he has been called — we find the spirit which characterises our modern charity hospitals. In the oath by which he bound himself to his profession there is the declara- tion that he would all his life visit the sick and give them his advice gratis — RAXSOHOFF MEMORIAL VOLUME a resolution which would certainly bring him a large practice, resembling tlie out-patient department of a hospital : and, indeed. Pindarus tells us of houses in Athens, officially chosen, where the sick poor repaired at fixed times — in fact, dispensaries. \\'e meet. also, with one allusion to a ho>pital. This institution is mentioned by the comic poet. Crates, whu lived about the middle of the fourth century B. C. That medical science had attained a high degree of iH'rfection in Egyp; may be inferred from the fact that there were specialists in different branches of the art. and each physician was allowed to practice only his own branch. The Egyptians had oculists and dentists, the latter of whom were skillful enough to be able to stop teeth with gold, as the Theban mummies show. Moreover, one of their kings — Athothis. son and successor to Menes. the first king of Egypt — wrote a treatise on anatomy. At what period medical science in Egypt emancipated itself from superstition is uncertain; but a medical papyrus, now at Berlin, which dates from the fourteenth century r>. C, contains a copy of a treatise on inflammation, which, the papyrus states, was found written in "ancient writing" rolled Uj) in a cotter, under the feet of Anubis, in the town of Sokheni, in the time of his sacred majesty, Thot the Righteous. After the death of this monarch it was handed to King Snat, on account of its importance. It was then copied and restored to its place under the feet of the statue, and sealed up by the sacred scribe ;uid wise chief of the physicians. In India. King Asoka. who reigned in the third century 11. C , published an edict commanding the establishment of hospitals throughout his domains. Monarchs and their advisers seldom invent — they systematize; and it is more than probable that King Asoka's edict was meant to improve rather than to initiate a hospital system. The king's edicts are still e.xlant ; for they are engraven in the living rock in Gujerat. not far from the town of Surat ; and there is also a legend that, grievere her death, after her cases had been in an acute state, with marked mental symptoms for three months. She had the treai- ment for only a week and I saw her but once, and she was practically mori- bund at the time. A second patient in this group, who had an attack several years before, at first improved both in weight (she had lost thirty pounds), in her general nervous condition, and especially in the pulse rate, which dropped from 120 to 84 per minutes in the course of ten days. She con- tinued to do well under the treatment for three months and then while taking the ext. corpus luteum had a very acute exacerbation with a pulse rate of nearly 200 and signs of great exhaustion and collapse. She was operated upon and the partial removal of the thyroid was followed by relief, but not by a cure, all of the symptoms of Graves' disease being present eight months after the operation. One other very acute case was not benefited by the treatment according to her statement, although the cliiiical record of her case shows that her pulse rate at the first examination was 140 beats per minute, and a week later was 108. She discontinued treatment and when seen at m\- re(|uest a year later was in a very acute state of Graves' disease. One of the exceedingly acute cases was a man, the only one treated. Bed rest improved him for a while, but later on he had a very acute relapse. Not knowing of any reliable preparation of the interstitial glands of the testicle, I placed this man on the ext. of the anterior lobe of the pituitary gland and he showed marked improvement while under this treatment. Later on he passed from under my supervision. All of the other cases have improved under the treatment, all of them have the ordinary routine treatment and in addition to hygienic measures and partial rest I combine the extract of corpus luteum 0.12 with quinine hydrobrom. 0.12 and ext. belladonna 0.006 per dose. Only one of these cases is really cured. But all the others are improved and very comfortable. The most notable impro\ement and the one most quickly noticed are the the cardio-vascular symitoms. The pulse rate drops very quickly and the disagreeable sym])t(inis caused by the disturbance of RAXSOHUl'f MEMORIAL VOLUME circulation quickly subside. Then the general nervous irritability dimin- ishes and the ]iatients all return to a more or less normal condition. I have found, however, that the i)atients often show a tendency to relapse and have remissions if they stop the ext. corpus luteum. If the above theory of the relation of the corpus luteum and the thyroid gland is correct, this is what we would expect. If Graves' disease is synonymous with hvpovarie, with a dysfunction or a diminished function of the corpus luteum. we would get results just as those recorded above. The Graves' symptom-complex arises as a result of a defective or deficient secretion of the corpus luteum. If we replace the deficiency by the use of ext. of corpus luteum we relive the patient and impro\e her condition. \\'e cannot, however, change the defec- tive biological activity of the ovary and make a defective ovary produce a normal corpus luteum. ,\nd this is the experience in my cases. Nearly all of them require the extract continuously, sometimes one dose of the above combination per dav will suffice. Others require two or three doses per day. In some of the cases there are periods of months when they are apparently free from all symptoms of Graves' disease and we may interpret these periods of remission as occurring during the time when the ovaries ]}roduce normal corpus luteum. I believe that Graves' disease in this respect can be compared with luyxe- dema and hypothyroidism ; as long as we administer thvroid extract in these two conditions, the patients are fairly normal. As long as we admin- ister corpus luteum in Graves' disease or in the ])eriods of exacerbation, the jiatient is improxefl and can be kept in a fairly normal state. lilBUOGU.VPllV. I,. Fiacnkrl. .\nh. f. C.ynaik.. 1903. Vol. 58. page 4.i>!. v.. Xov.nk. Join. .\.ii. Med. .\s5n.. 1916. Vol. 67. paRf 1-'8.V FaltaMeyer. Tlie Ductless C.landular Diseases. P. Blakistoirs Son and Co. -'ml edilian. Seitz-Wintz and Fingeihut. Munch. Med. W'ochcnsch.. 1914. No. 30.,11. Hammonds and Marshall. Proceed. Royal Society. London (B). 1914. page Ml. Pearl and Surface. Science. 191.S. Vol. XU, page 61,=i. Claude and Gougerot (Falta). C.az. d. hop. 191.'. No. 57. 849. E. Hcrtoghe. Med. Record, 1914. II. THE TREATMENT OF HYPERTHYROIDISM \\TTH CORPUS LUTEUM: A SECOND REPORT.* H. H. HcippK, A. M., M. D. Cincinnati 'I'hc treatincnt of Graves' disease is an ever interesting and important topic for discussion. The fact that there is hardly a meeting of surgeons without a paper or even a symposium on the surgical treatment of Graves' disease and the wide- spread discussion of the papers shows that the surgeons have not solved the problem, notwithstanding the vogue which the surgery of the thyroid enjoys at [iresent. The numerous methods of treatment on a i)Urely hygienic and medical basis and the published results of treatment is also a proof that the results of treatment from a purely medical stand])oint are far from being satisfac- tory. Both the surgical and medical methods of attack are defective for the reason (hat both approach the problem from a symptomatic standpoint. THK \VE.\KNESS OF SURGICAL AND Dl^UG TRE.\TME.\T. The weakness of the surgical approach is that its aim is to remove the thyroid gland which is not the primary scat of disturbance but merely an expression of disordered function, whose causative seat is located in some other portion of the body. This accounts for the fact that, while undoubt- edly many cases are benefitted by surgical intervention and many distressing symptoms are relieved, many of the patients, months and years after the operation, still show most of the classical signs of the disease, notwithstand- ing the removal of the thyroid gland. The operation has merely made the patient's condition more tolerable. The purely drug treatment inclusive of the treatment for intestinal auto- intoxication is not often successful because it is purely symptomatic. What- ever results are obtained are the results of nature's own recuperative powers, assisted by rest and other hygienic measures. The ideal treatment should be based upon an etTort to find and remove the cause of hyperthyroidism. THE CAUSE OE EXCESSIVE THYROID EUNCTIO.V. It is generally conceded that hyperthroidism is an expression of an unbrd- anced state of the chemical mechanism of the endocrine glands. The over- acti\ity of the thyroid is never primary. It is unthinkable that, without any apparent cause, there should suddenly be present a state of excessive func- tion of the thyroid. Hence our first approach toward a rational treatment ♦Read bffure the Section on Nervous ami Mental Diseases of the Ohio State Medical .Vssociv lion. during the Seventv-fourth Annual Meeting, at Toledo, June 1, 1920. From The Ohio State .Medical Journal. October, 19J0. RAXSOHOFf .MEMORIAL VOLUME of hyperthyroidism should be an endeavor to discover the cause ; why the function of the thyroid, which previously has been normal, should now be excessive. The second indication of treatment is to overcome and remove the effects, on the body as a whole, of the over-activity of the thyroid gland. The results of the over-activity of the thyroid manifest themselves grad- ually and progressively on nearly all the organs and functions of the body. A whole train of signs and symptoms which may be looked upon as a result of the presence in the circulation of an excessive amount of thyroid secre- tion, gradually develops, which is an expression of disordered metabolism and hence, of parenchymatous changes of the tissues of all the organs of the body. Many of the efifects of this disordered function persist even after the thyroid has been removed. These changes, primarily the result of toxic action of thyroid over-activity, persist even after all possiblity of thyroid action has been removed and hence demand special treatment, irrespective of the proximal cause. The persistence of these syiiiptoiiis is the best proof that, although they arc originally caused by hyfcrtliyroidisiii. the later condi- tion is merely a secondary cause, the primary cause being some other remote organic or functional derangement of one of the otiier endocrine glands. If this were not true such signs as exophthalmos, tachycardia, tremor, and excessive metabolism, should not jiersist years after the removal of the thyroid gland. GEXER.\L COXSIDERATiOXS OF TKE.\TM1'\T. \\'e shall endeavor to place before you our experience in the treatment of hyperthyroidism extending over a period of five years and embracing about fifty cases. These embrace all degrees of hyperthyroidism from the mild to the most acute. None, however, were doubtful cases, the diagnosis in all being based upon the classical symptoms plus the presence of a distinct bruit in the thyroid gland. We believe that the good results in the treatment of these cases were due to the use of the extract of corpus luteum : In treating this subject let us consider: 1. The function of the thyroid gland. 2. The relation of the thyroid to the other endocrine glands. ,1 The histology and the function of the corpus luteum. 4. The clinical results obtained in the treatment of hyperthyroidism with the corpus luteum and the theory on which the treatment is based. THE FUXCTIOX OF THE THVKOH). 1. It seems to be fairly well establi.shed that the regulation of metab- olism is one of the chief fimctions of the ductless glands and that the special function of the thyroid is the regulation of proteid metabolism. W'e see, therefore, an increase in basal metabolism in hyperthyroidism and a decrease in basal metabolism in hypothyroidi>m. Felta divides the ductless glands into HERMAN H. HOPPE two groups according to their physiological function, the acceleratory group and the retardative group. Through their hormones these glands exert an antagonistic effect on the metabolism of the body. The thyroid gland, through its hormones, quickens metabolism and increases excitability. We see this typically in hyperthyroidism in which an excess of hormones is produced. In myxoedema we have an arrest of growth due to an inhibition of metabolism, because of a deficiency in pro- duction of the hormones of the thyroid. RELATION TO OTHER ENDOCRINE GL.ANDS. 2. Opposed to the acceleratory group of glands are those of the second group which have the opposite or retardative action. They build u]i and stim- ulate assimulation. In this group we have the interstitial glands, the testicles and the ovary. We have, therefore, an antagonistic action between (he thyroid gland and the sex glands and we will assume for the present, with an cfTort later on to ofifer proof, that the sex glands act as an inhibitory agency on the thyroid gland and that when there is an absence of the specific secrete of the inter- stitial, sex glands and the other ductless glands are unable to make the compensation, we will have an excessive function of the thyroid gland. FUNCTION OF THE CORPUS LUTEUM. 3. We know that the specific hormone of the testicle is produced by the interstitial tissue. For the ovary, the proof of an interstitial secretory tissue has not been so well established. We shall try to offer proof that the spe- cific hormone of the ovary is produced by the corpus luteuni. Fraenkel published a paper on the structure and origin of the cor|nis luteum, in 1903. Novack studied the relation of the corpus luteum to men- strual disorders and his research into its origin, structure and physiology is most critical and exhaustive. Other investigations have shown that the corpus luteum influences the development and function of the mammary gland and also that it affects the developments of secondary sex characters. Let us consider somewhat in detail, what we know of the corpus luteum to-day. In a previous article we sought to establish the fact that the cor]nts luteum secretes the specific hormone of the ovary and is therefore a duct- less gland. We know that the corpus luteum is the final stage of the devel- opment of the Graafian follicle. Novak made a careful study of one hun- dred and thirty-seven ovaries which had been removed during operation on the pelvic organs and he concludes that the corpus luteum is epithelial in character and that it is derived from the epithelial cells of the membrana granulosa of the Graafian follicles. Myer and Sobotta had ])reviously come to the same conclusion as to the origin of the corpus luteum in lower animals. The corpus luteum contains two kinds of specific cells — the lutein cells and the paralutein cells. These cells cover a very rich network of newly Page l".'i RAXSOHOFf MEMORIAL rULUME formed blood vessels. It is held, therefore, that these cells, the lutein and paralutein cells, being epithelial, have a secretory function, that they pour their secretion directly into the blood vessels upon which they are imbedded and (hat the corpus luteum is therefore a ductless organ. The most important function of the corpus luteum is the reKulatiim of the sexual life of woman. The hormone of the corpu^ luteum acts in a two-fold way: (a) A local action on the uterus and perhaps the placenta. (b) A general one, liz., the regulation of the metabolism underlying the development of the secondary sexual characteristics, seen especially perhaps in the mammary glands. In regard to the first function Novak says: "There can be but litt> doubt that the corpus luteum has at least a dual function, (a) the causatioi- of menstruation; (b) the preparation of the endometrium and the fixation of the ovum in the earliest stages of pregnancy." Xo\ak goes further and states that he has observed in ovaries in which the paralutein cells were present in large numbers in the corpora lutea. the patients suffered from pro- fuse menstruation, irregular periods and sterility. He believes that the luiein cells stand in relation to menstruation and that the paralutein cells have som: relation to ovum fixation. Seitz. W'intz and Fingerhut think that they have isolated the hormone'; of the corpus luteum and claim that it secretes two active principles which are opposite in their activity in relation to the functions of menstruation and pregnancy. 1. Luteolipoid which has an inhibitory influence on menstruation and when injected hypodennically diminishes the excessive flow in menorrhagia. 2. Lipanin, which in animal experiments, stimulates the development of the sexual organs and in human beings when administered hyi)i)dermically in amenorrhoea brings on the menstrual flow. Hammond and Morhall ha\e made observalion> on the relation between the corpus luteum and nianunary glands and F'earl and Surface on the sec- ondary sexual characteristics. It seems demonstrated, therefore, that the corpus luteum ha> an all im- portant influence, not only on menstruation and jiregnancy. but also on the general metabolism of the bodv. in so far as the secondary sexual charac- teristics are concerned. There can be no doubt that other organs of internal secretion also have an influence on the regulation of the metabolism under- lying secondary sexual characteristics and that these organs stand in rela- tion to ovarian activity and that they are therefore in relation to the corpus luteum and that the latter organ i> therefore the avenue ihmugh which the other ductless glands exert their influence on tlie functions of the female generative organs. If these contentions of .Xovak, Me\er :uk1 Snbatta. that the corjius luteum is an epithelial gland and that according to Novak its function is to regulate Page HERMAN H. HOPPE menstruation and ovum fixation, and if the observation of Seitz, Wintz, Fingerhut, Hammond, Marshall, Pearl and .'Surface on its relation to sex characteristics and mammary development are true, then there is at least some proof that there must be a specific secretion poured from the cells of the corpus luteum into the general circulation and that therefore, the corpus luteum is a ductless gland and secretes the specific hormone of the inter- stitial tissue of the ovary. A defective development of the corpus luteum, therefore, would tend to produce a lack of balance of the endocrine system. IXTKR-RKLATIOX BETWEEN THE THYROID .AND OVAin'. We know that there is often a lack of proper development of the Graafian follicle. In these cases the follicle does not reach maturity, it does not burst, but degenerates, undergoes liquifaction and disappears — the corpus luteum is not formed. If the corpus luteum is not formed the specific hormone of the ovary is lacking and the chain of ductless glands is unbalanced. \Vhat proof have we to uphold Felta's contention that there is a relation and perhaps an antagonistic relation between the thyroid and the ovary? We have seen above that Felta places the thyroid gland in the group of those glands whose hormones accelerate the metabolism of the body by increased ovidation and increased excitability of the tissues, whereas he places the hormones secreted by the interstitial tissues of the sex organs in the antagonistic group, I'ic, those whose function is to build up instead of breaking down, hormones whose function is anabolistic instead of katabolis- tic — assimilatory and retardative in function. Our therapy is based upon the antagonistic action between ili\niitl and ovary or corpus luteum which we consider the specific endocrine uland of the ovary. Clinicall}' there is abundant proof of the interrelation of thyroid and sex life. In man the sexual function is an incident. In woman sexual function is the chief function of metabolism. We find, therefore, that disturbance of the thyroid activity in adults is found chiefly among women. Women are affected at least six times oftener than men and in my experience the pro- portion of women affected is still greater. In women. Graves' disease occurs almost always during the period of sexual life. It begins very often around puberty and its course, especially during acute exacerbations or in grave cases is attended with a suspension of the menstrual function. Graves' disease is rare before ])uberty and after the menopause. INFLUENCE OF PREGNANCY. Many women with Graves' disease do not become pregnant. This would seem to prove that a normal ovum and a normal Graafian follicle are not pro- duced in these cases. We know that Graves' disease is subject to exacerba- tions and remissions. Pregnancy does occur and in some cases has a bene- Paac I'.a RAXSOHOFF MEMORIAL VOLUME ficial effect on the course of the disease. In others pregnancy has ;i decid- edly bad effect. In api)arently cured cases pregnancy can bring on an acute attack. I'his (XTradcxical effect of pregnancy on Graves' disease may be explained by the fact that when the corpus luteum of pregnancy is normally developed there is an improvement in the symptoms of the patient and when the corpus luteum is functionally deficient there is an exacerbation of the symptoms. We would like to explain the fact that some patients may go through one pregnancy without any difficulty and the next may cause very alarming manifestations of hyperthyroidism, on this basis of either a normal or deficient corpus luteum of pregnancy. On the same groimds we would like to explain the exacerbations and remissions ordinarily seen in Graves' disease when untreated, vie. when the rupture of the Graafian follicle is fol- lowed by the development of a normal corpus luteum, the sym]itoms amelio- rate and vice versa. A further proof of the inter-relation of the corpus luteum and the thy- roid is offered perhaps by mild cases of myxoedema which show a normal thyroid activity between menstrual periods and an active myxoedema during the menstrual function. This would seem to indicate that the corpus luteum exerted an inhibitory effect on the thyroid in these cases and that a thyroid gland, which was capable of performing its function fairly normally during the intermenstrual period, lost its ability to do so during the period of the greatest activity of the corpus luteum. (Hertoghe; Medical Record, 1914.) Moreover, the same antagonistic action is seen in absolute Cretins who never arrive at the stage of puberty. In addition to these facts, our clin- ical experience would warrant our assertion that this inter-relation of thy- roid and corpus luteum resolves itself into the fact that the specific hormones excreted by the corpus luteum exerts an inhibitory effect on the thyroid secretions and that hyperthyroidism is an expression of dysfunction of the corpus luteum in the female and perhaps, although we have not had much experience, of the interstitial glands of the testicle in the male. This view is also held by Claude and Gougerot, who call Graves' disease a hypo- ovarial disease OBJECTION TO THE THEORY. The most serious objection to this theory is that we rarely see a typical Graves' disease symptoms complex following the removal of ovaries or tes- ticles. The vast majority of individuals, however, have a normal endocrine system. After a more or less prolonged period, when one gland is dis- turbed or diseased, it is possible for other glands to make the compensation. We know, for instance, that after castration in the human family as well as in animals, and during pregnancy for instance, there is marked increase in the size of the pituitary gland and that this enlargement means an increased function by means of which the endocrine balance is restored and main- tained. Ovaries and testicles arc removed onlv as a rule when thev are HERMAN H. HOPPE diseased and when their function has been perverted for a long time and nature has had ample opportunity to establish a compensation before the operation. It is only perhaps in individuals in whom this balance cannot be established for some reason, that a dysfunction of the interstitial sex glands is followed by hyperthyroidism. In two cases at least the use of the anterior lobes of the pituitary gland was followed by relief in male cases of Graves' disease, and Renon and Delille saw a Graves' disease symptom complex dis- appear as the result of the simultaneous administration of pituitary and ovarian extract. It is essential to prove, if the above theory is correct, that the symptoms of Graves' disease are due to an excessive secretion based upon an excessive function of the gland rather than to a toxic secretion and that the manifes- tations of Graves' disease are due to increased thyroid activity. THYROTOXICOSIS OR HYPER-.^CT1VITY? There have always been two theories on which the development of the symptoms of Graves' disease have been based, viz., the toxic theory and theory of excessiz'e secretion. The toxic theory is based upon the assump- tion of a perverted function of the thyroid gland. This theory is probably on the wane, the results obtained from surgery would seem to lead to this conclusion and the almost universal adoption of the terms hyperthyroidism and hypothyroidism would seem to indicate that the abnormal activities of the thyroid gland are due to either an excessive or a deficient secretion of the thyroid tissue. According to Felta we do not need to assume a perverted function of the thyroid, in Graves' disease, that poisoning and excessive secretion are synonymous terms. A normal secretion poured into the cir- culation in excess will poison the body. Felta calls our attention to adrenalin jioisoning as a fitting example. The .symptom complex of Graves' disease, especially the serious cases, undoubtedly points to pluriglandular disturbance. But we need not assume that we have therefore a pluriglandular disease, for we cannot have a marked hyperfunction of any one of the endocrine glands without disturbing the finiction of most, if not of all of them. The theory on which the use of cor])us luteum is based is that Graves' disease and hyperthyroidism are ef|uivalent terms. THE CORPUS LUTEUM TREATMENT OF HYPER-THYROIDISM. 4. I have been using the corpus luteum now for six years. I was impelled to try it at first on a very acute case of Graves' disease because of the presence of amenorrhoea which had persisted for a year. This patient had had prolonged rest and the us-ial medicinal remedies, but went from bad to worse. She had lost sixty pcunds in weight. This patient made a complete recovery and has remained well for the past five years. Since my last report in 1918, I have treated twenty-five additional cases and have RAXSOHOfF MEMORIAL VOLUME had most of the cases reported previously under observation and have seen them from time to time. None of these tifty cases were doubtful cases. In making the clinical diagnosis of hyperthyroidism, I have established for myself the rule that, if there is no bruit in the thyroid gland. I do not make ihe positive diagnosis of hyperthyroidism and place the cases in a doubtful catagory. All of the above cases were diagnosed as positive cases on the above test. One of the cases reported in 1917, has died of influenza, all the others are doing well and some of them seem to have established a normal balance of the endocrine glands and do not take corpus luteum. The others are comfortable when they take corpus luteum. I have had no cases of hyperthyroidism operated on since 1917. In the last group of twenty-five cases one man died twenty-four hours after I had seen him in consultation. The patient had had hyperthyroidism for years — was in an acute relapse at the time of the consultation and was sutferiug from and died of acute myocardial disease leading to cardiac dila- tation. Three or four of these cases were very acute — one had lost sixty pounds and the other seventy pounds — both of these latter cases have made practically a complete physiological recovery and have taken up their former occupations. Both were women. Both had extreme cardio-vascular symp- toms, exophthalmos, diarrhoea and rapid emaciation. One, the wife of a physician, has made a perfect recovery; the other has still some exoph- thalmos, and an enlarged thyroid, but insists that she is well and has worked in a factory for the past year. This second group contains a surgical case which had the thyroid removed, but still presented all the objective signs and subjective distress of hyperthyroidism. She has improved under the treat- ment. Three of the other cases are very much improved, all of them are satisfied and relieved. In the latter group of cases there is but one male and lie has done well on extract of pituitary gland. DET.AILS OF TREATMEXT. The most notable and the most rapid improvement is seen on part of the cardio-vascular symptoms and general nervous manifestations. The pulse rate drops quickly, the general subjective symptoms caused by the circula- tory disturbances subside, the loss of weight stops, digestion and appetite become normal, the nutrition improves and the patient takes on weight. While I look upon the corpus luteum as the specific agent in the treatment of Graves' di.sease, I have not discontinued the symptomatic treatment, nor the attention to hygiene and diet. For after Graves' disease has been estab- li.shed. we see signs of pluriglandular disturbance. The digestive disturb- ances, the increased metabolism and the rapid emaciation all demand symp- lomatic treatment. On account of the general nervous and mental irrita- bility, cases of Graves' disease are not very easily managed, nor are they as a rule faithful to the treatment. I give careful attention to the diet, allow very little i)hysical exercise and i)rescribe much bed rest. Quinine hydro- Paije >m HERMAN H. HOPPE hroniate and extract of belladonna are of great value. I usually give rwo grains of corpus extract, three grains of hydrobromate of quinine and one- tenth grain of the extract of belladonna after each meal. After the cases show improvement, I diminish the dose to two per day and even when the patients are apparently well, I still give one dose per day, usually at bedtime. .'\.s in my previous report, I still find that patients who take tlie treatment irregularly or who discontinue the treatment show a tendency to relapse and to have an exacerbation of all symptoms. We believe that the exacerbations and remissions which are ordinarly seen in Graves' disease are due to the fact that defective ovaries may occasionally produce even several months in succession normal corpus luteum, and during these periods show an improve- ment. We believe that in the cases which have recovered, the use of the corpus luteum has tided the patient over and assisted the patient in estab- lishing a compensatory secretion by one of the other endocrine glands and thereby bringing about once more an endocrine balance with a permanent relief of all the symptoms. CONCLUSION. The theory on wliich the above treatment is based, therefore, is that hy])erthyroidism is caused by a defective secretion of the interstitial sex glands ; that the hormones of the interstitial sex glands have an inhibitory and regulatory action on the secretion of the thyroid; that when the function of these interstitial glands is deficient, there is a lack of physiological inhibi- tion of the thyroid, with an excessive secretion and therefore, hyperthyroid- ism. In other words, hyperthyroidism and hypo-ovarianism are synonymous conditions. As I have said before, the mere administration of corpus luteum alone will not relieve these cases. Even a superficial knowledge of Graves' disease would disabuse our minds of this idea. The cases require careful dietetic, hygienic and symptomatic treatment. r)Ut whereas my previous experience has been that most cases with the above symptomatic treatment combined with quinine hydrobromate and extract of belladonna showed but inditifercnl results, the use of corpus luteum. in conjunction witli this general treatment, gave most satisfactory results. The treatment of hyperthyroidism with corpus luteum is comjiarable with the treatment of myxcedema with thyroid extract. As long as we administer thyroid extract, cases of myxoedema and hyperthyroidism do very well. Rut the administration of thyroid extract will not make a defective thyroid resume a normal function. Xor will the administration of corpus luteum cause a deficient ovary to produce a mature Graafian follicle. But it has been my experience that, as long as we administer corpus luteum in Graves' disease or in its period of exacerbation, the patient is improved and can be kept in a fairly normal condition. I. THE X-RAY EXAMINATION OF THE MASTOID REGION* By Samukl Iglaueu. B. S., M. D. Cincinnati. Ill many branches of medicine and surgery the Roentgen rays have be- come almost indispensable as an aid to diagnosis, and frequently the nature of some obscure condition is absolutely determined by the radiogram. The value of radiography has become well established in the field of rhinology, especially in the examination of the accessory cavities of the nose, so that sinusitis, or tumors of the antrum of Highmore, of the ethmoids, and the frontal sinus, can be definitely outlined. Radiography in rhinology not only lays bare pathologic conditions, but also gives valuable aid in outlining anat- omic relations, so that the surgeon may proceed with greater assurance in opening these cavities when they are diseased. Thus Beck,^ after obtaining an exact outline of the frontal sinus in the skiagram, turns down the anterior wall of the sinus and subsequently replaces it by a plastic operation. Ingalls- (loes not hesitate to drill into this cavity by the nasal route, after he has determined its anatomic position in the radiogram. To Caldwell' belongs (he credit of having established the projier angle for the delineation of both frontal sinuses upon the same plate. In exposing the temporal bone to radiographic examination, greater obstacles are to be met with than in examining the sinuses and bones of the face, because it is difficult to obtain a profile of one temporal bone without superimposing upon it the shadow of the other. In fact, the chief difficulty in radiography of the cranium is to establish the proper angle at which the picture is to be taken, in order to ;ivoid the shadows of tlie thicker portion of the skull. Thus \'oss'' and Winckler,"' b)- taking pictures in the transverse diameter of the skull, report excellent results in outlining the mastoid region as well as determining its condition of health or disease. Kuhne" and Plagemann' prefer taking pictures in the occipito-frontal direction, since thereby an image of both mastoid processes is obtained at one time and upon the same plate. Judging from the illustrations accompany- ing their article this method is open to objection, since the temporal bone is too far removed from the plate to give a sharp image, and only a portion of the mastoid process appears in the Roentgen picture. Considering the difficulties frequently encountered in diagnosticating dis- eases of the mastoid process, it has for some time past seemed advisable to me to obtain radiograms of the mastoid region, and I was fortunate in having an expert radiologist. Dr. S. Lange, kind enough to undertake this work. To him I am indebted not only for his untiring etiforts, but also for valuable suggestions. •Thesis presented to the .American l.aryngolo^ical. lihinolo^ical and OloIoKie.-il Soeicty, Janu- ary 1, 1909. Keiirinldl from Annals of Olulogy, Rhinology and Laryngology, Ueiemher, 1909. Paijc mi SAMUEL IGLAUER The greatest obstacle to be overcome was in establishing the proper angle from which uniform resuUs might be expected. At my suggestion the obHque profile of the temporal region was employed. Subsequently Dr. Lange suggested taking measurements of the angle of inclination of the X-ray diaphragm, so that greater precision might be liad. These points will be further elucidated in describing the technic. We have taken radiograms of the dry skull, of the cadaver and of a considerable number of patients. In all \vc have collected about fifty plates. I 1 " M ,ml 1 B ■■ 1 i 7 V / 9 Jb Radiography of Mastoid Region, showing relative positions of plate, X-ray dia- phragm and patient's head. Note the inclination of the X-ray diaphragm. (The radiograms may be taken to advantage with the patient lying on his side, but with the diaphragm in the same relative position as in Fig. I. Page m.l RAXSOHOFF MFMORL-iL VOLUME of the mastoid process For the same reason a .. The auricle is then TECHXIC. 'I'he technic is as follows : A small piece of lead foil is plastered to the tij ill order to fix this point in the Roentgen picture, coil of wire is introduced into the auditory meati drawn forward and fastened by adhesive plaster to the cheek of the patient in order to hold it away from the mastoid region. The patient then lies on his side on the table, or sits upon a chair, with the ear to be examined in contact with the photographic plate. The diaphragm of the X-ray tube is then adjusted immediately below the parietal eminence on the opposite side of the patient's head, and is given a slant, so that the rays will be directed through the cranium toward the sigmoid sinus and mastoid process of the car which is being radiographed. ( See Figs. 1 and 3.) In this position, the temporal bone on the upper side of the skull is left almost entirely out of the radiographic field. Dr. Lange has measured the angle of inclinalioii of the axis of the diaphragm and finds it to be as follows: FIGURE 11. . Quarter section of a skull with lead foil in the sinus, and a wire in the auditory meatus and in the middle fossa. (P F) Posterior fossa. (E) Foramen for emissary vein. (Arrow) Indicates descending portion of facial canal. (O) Orbit. (Z) Zygoma. Page 20 i SAMUEL IGLAUER First, it is inclined 25 degrees to the basal plane of the skull, and sec- ondly, it is tilted backward 20 degrees from the coronal plane of the skull. (See Fig. 1.) This step of the technic is very important because it assures uniform results. The lime of exposure \aries from 20 to 50 seconds with an electrolytic interrupter, to four minutes with a mercury turbine interrupter. For com- parison it is advisable to radiograph both temporal bones at the same sitting. Figure 2 shows a quarter section of the dry skull, in which some of the landmarks are brought out by filling them with lead foil. This experiment enables the observer to fix the anatomic relations in subsequent pictures. 'I'his radiogram shows very well the internal structure and relations of the temporal bones and requires no further description. The next illustration (Fig. 3) shows the mastoid region traced from a radiogram taken through the entire skull. The anatomic structures are here FIGURE Radiogram of a dry skull, showing left mastoid region taken in an oblique profile. The lower shadow (X) is the right mastoid thrown out of the field by the oblique direction of the X-rays. (M) Meatus. (T) Tegmen, (S S) Sinus. (P) Styloid process. (Arrow) Facial canal, in the mastoid. (Z) Zygoma. (O) Orbit. (B I Floor of post-fossa. Page _"/.; RAXSOHOFF MEMORIAL VOLUME Print and tracing from plate of a normal mastoid region in a voung woman. (*) Meatus. (X) Mastoid cells. fS S) Sinus. (M^ Mandible. (E)' Middle fossa. FIGURE V. Tracing from a radiogram of a normal, left mastoid in a man of i7 . (*) Meatus. (T) Large cell in the mastoid tip. (F) Middle fossa. (S) Sinus (?). (L L) Suture lines. (M) Mandible. (O) Orbit. Paai- nii; SAMUEL IGLAUER very distinct, and it will be observed that the one mastoid is entirely out of the field. Figures 4 and 5 are tracings from radiograms of norma! mastnid regions in different patients. It is impossible to re])roduce some of these plates except by tracings. These illustrations show the relative position of the middle fossa of the skull, the outline and cellular arrangement of the mas- toid process, the position of the external auditory canal and frequently of the sigmoid sinus. As may be judged from the illustrations, practically all of the skiagrams delineate very accurately the anatomic relations of the mastoid process. Considering the great variability in the structure of the temporal bone, it is apparent how valuable this knowledge obtained prior to an operation may become. Indeed, should radiography give no further information than this, it would still repay the otologist to obtain those Roentgen pictures. As a matter of fact, however, the skiagrams reveal not only anatomic relations, but also, in some cases, pathologic process in the interior of the mastoid process. In certain cases of chronic suppurative otitis media the radiograms showed practically an absence of mastoid cells, the sclerosed bone throwing a den.se shadow. Such pictures were obtained in five cases. (See Figs. G and 7.) In four instances the Roentgen pictures were confirmed by oper- ation. In one case, that of a man 21 years, with chronic otorrhea, osteosclerosis was diagnosticated in the right ear, with the probable absence of mastoid cells. (Fig. 7.) The left ear taken at the same time for comparison, showed a massively developed pneumatic process. Operation revealed a dense mastoid process with a very small antrum, which was only uncovered after working according to the method of Stacke. A second operative case was that of a boy of twelve, with chronic sup- puration in the left ear. The sinus, the tegmen tympani and the mastoid process were found exactly in the condition indicated by the picture. (Fig. 8.) The third case was one of tuberculosis of the middle ear in a man of forty-five. The two radiograms, taken at intervals before the operation, showed a very large mastoid process of pneumatic type with hazy outlines of its cells. Operation revealed a large mastoid process with numerous large cells, most of which were filled with a clear serous fluid. The middle ear and antrum contained granulations. (Fig. 9.) The fourth case was operated upon too recently for description. From the experience gained by this investigation, the following conclu- sions may be drawn : First. It is quite feasible to radiograph the mastoid region. Second. The best skiagrams are obtained by directing the rays so as to give a slightly oblique profile of the temporal region. RAXSOIIOFf MliMORlAL lOLUME FIGURE Tracing from a radiogram. Right mastoid region in a case of chronic otorrhea )f many years' standing. Note absence of mastoid cells, t. c, osteosclerosis. (S) For- vard-lying sinus. (M) Mastoid. ^A) Meatus. (T) Tegmen. (R) .■\scending ramus .f mandible. (Patient of Dr. William Mithoefer.) (Case !.■) I-. K. Right n\ast(iid region, .showing: (P P) Osteosclerosis of mastoid. (S S) Sigmoid sinus. (M) Mandible. (M F) Middle fossa. (C) Meatus. (Confirmed by operation.) SAMUEL IGLAUER (Case II.) Tracing from a radiogram. Left mastoid region. (M) Meatus. (M F) Middle fossa. (C C) Mastoid cells. (S) Anterior border of sinus. (J) Man- dible. (L L) Suture lines. (O) Orbit. (X) Top of mastoid. FIGURE IX. (Case III.) Radiogram tracing tuberculosis of middle ear and mastoid. Large mastoid of pneumatic type. Cells appear hazy in the radiogram. (Confirmed by operation.) (*) Meatus. (S) Zygoma. (O) Orbit. (M F) Middle fossa. ( I) Man- dible. RAXS'OJIOff MEMORIAL I'OLUMIl Third. The radiogram distinctly outlines the anatomic relations of the external auditory meatus, the limits of the mastoid process and of the mas- toid cells. The floor of the middle fossa of the skull is shown, as well as the thickness of the tegmen tympani. The sigmoid sinus is frequently delineated and its position indicated. Fourth. Osteosclerosis of the mastoid bone, following prolonged otorrhea, may in some cases be determined by the X-ray examination. Fifth. It is possible that pus and granulations (\'oss). as well as seques- tra (Winckler), in the mastoid process can be diagnosticated by means of the X-ray. It must be stated, however, that acute inflammation of the mucosa is difficult to differentiate from softening of the bone ( Plagemann). Sixth. In general it may be stated that radiography should prove of great value in the determination of both the anatomic and pathologic condi- tions within the temporal bone. niBLIOGR.NPHV. 1. Jos. Beck. Jour. Am. Med. Assoc.. August 8. 190«. 2. E. Fletcher Ingals. Jour. Amer. Med. Assoc. May 9. 1908. 3. E. W. Caldwell. Amer. Quar. of Roentgenology, January, 1907. 4. O. Vos. Verhand. der Deutsch. Otologischen Gesellschaft, May. 1907. Reprint puli. by Gustav Fischer in Jena. Also Ref. Zeitschrift f. Orenheilkunde. Ed. LI\'. Heft J. p. 208. Jiilv. 1907. 5. Winckler. Zeitschrift f. Ohrenheilkunde. Bd. LIV. Heft 2. p. 209, July I, 1907. 6. Kuhne and PlaRemann. Fortschritte auf dem Gebiete der Roentgenstrahlen. Bd. .XII. Heft 5. September 1. 1908. 7. Plagemann. Verhand, der Deutsch. Roentgcn-Gescllscliaft. IJd. \\. September, 19U8. THE CLINICAL VALUE oF RADIOGRAPHY OF THE MASTOID REGION.* SAMUEL ICLAUKK. U.S., M .D. Cincinnati. The difficulties encountered in radiographing the temporal bone are due to its position at the base of the skull, to the thickness of the parts that thi- Roentgen rays must penetrate, and to the liability of superimposing the shadows of other portions of the skull on the skiagram of the temporal bone. By directing the rays in the anteroposterior (posteroanterior) axis of the skull Kuhne and Plagemann'- ^ have taken radiograms of the projecting por- tions of both mastoid processes, and have drawn clinical deductions there- from. Voss^ and Winckler* have obtained more detailed Roentgen pictures of the temporal bone by directing the rays in the transverse diameter of the skull. During the past year Dr. S. Lange, radiologist to the Cincinnati Hos- pital, to whom I am greatly indebted, has been kind enough to undertake the radiography of the mastoid region for me. After some experimentation, at my suggestion, the radiograms were taken in an oblique profile, i. e., the rays coming from the target were made to center just below the parietal eminence on one side of the skull and vvere directed through the cranium in the direction of the temporal bone on the opposite side of the skull. At this angle the best skiagrams were obtained. In this position Dr. Lange found that the axis of the X-ray diaphragm was tilted upward at an agle of 25 de- grees from the base of the skull (Reid's line), and that it was inclined back- ward 20 degrees, from the vertical plane passing through both external auditory canals. Figure 1 illustrates this double inclination. In a previous paper on this subject^ I have given further details concerning the technic, and these need not be repeated here. RADIOGRAPHY OF THE NORMAL MASTOID REGION. In the normal subject ; skiagrams obtained by this method delineate the following: (1) The mastoid process with its cells; (2) the position of the external auditory meatus ; (3) the line marking the floor of the middle fossa ; (4) frequently the position of the groove for the sigmoid sinus. Many plates in addition show the floor of the posterior fossa, the as- cending ramus of the mandible and the suture lines radiating from the asterion. Figures 2 and 3 show all the landmarks above mentioned. From •Read in the Section on I^aryngology and Otology of the .\merican Medical .Association, at the Sixtieth Anniial Session, held at Atlantic City, June. 1909. 1. Kuhne and Plagemann: Fortschr. a. d. Ceb. d. Roentgenstr.. Sept. 1, 1908. xii, No. 1 2. Plagemann: Verhandl. d. Dcutsch. Roentgen-Gesellsch., Sept.. 1908, iv. 3. Vos. O.: Verhandl. d. Deutsch. Otol. Gesellsch.. Mav. 1907; reprint pub by Gustav Fischer in .Tena; also abstr. in Ztschr. f. Ohrenh., July, 1907, liv. 208. 4. Winckler: Abstr. Ztsch. f. Ohrenh.. July, 1907, liv, 209. RAXSOIIOFF MEMORIAL VOLUME Fig. 1. The arrow indicates the inclination at which tlie radiogram sliould be taken, i. e., the X-ray diaphragm should be tilted backward 20 degrees from the ver- tical plane, arid should be inclined upward 25 degrees from the horizontal plane. ( .\s measured by Dr. S. Lange.) these and similar ])lates it will be apparent that the internal anatomy of tht temporal bone may readily be determined by radiography. Considering the great variability in the structures of this bone, the knowledge so obtained prior to operation will prove of great value to the surgeon. R.\D10GRAPHY OF THE PATHOLOGIC MASTOID REGION. Among the pathologic cases examined were seven cases of chronic otorrhea, one subacute case and four acute cases. - In cases of suppuration of long standing, attended with osteosclerosis an(i obliteration of the mastoid cells, the dense bone shows very distinctly, and the sigmoid groove very often stands out sharply in the picture. The posi- tion of the antrum may be indicated if the overlying bone is not too dense. Fig. 2. Radiogram of mastoid region of a skull: (*) .Auditory meatus; (M F) middle fossa; (L) lead foil in middle fossa; (C) large cell at the mastoid tip; {C ) small cell; (S S) sinus ^marked by wires) ; (B) jugular bulb; (P F) posterior fossa; (O) orbit; (XX) suture. Paiji- ^1.1 ■ SAMUEL IGLAIJER Seven of the cases which had been radiographed came to operation and the X-ray findings were in a great degree confirmed. It may be interesting to recount these cases somewhat in detail. R.ADIOGRAMS CONTROLLED BY OPERATION'. Case \. L. K., male, aged 21. Diagnosis: Chronic suppurative otitis media on the right (of uncertain duration). X-ray examination showed a dense shadow over the right mastoid region, with the absence of cellular structure. The position of the sinus is indicated. The left normal mastoid region showed an enormously developed pneumatic process. Operation, August 28, 1908, confirmed the findings in the right ear. Fig. 3. Tracing from radiogram. Normal. Mastoid region of a child. (M F) Middle fossa; (C C) mastoid cells: (S S) sigmoid sinus: (J) jaw; (Z) zygoma; ( P F) posterior fossa. Remarks. — In this case it seems likely that the chronic suppuration retarded the development of the right mastoid Case 2. M. S., male, aged 12. Diagnosis: Chronic suppurative otitis media, right and left, of seven years' standing. X-ray examination showed a diploetic mastoid, a high tegmen, and the line marking the position of the sinus. .\ meatomastoid operation (November 21, 1908) showed the anatomic relations as in the radiogram. Remarks. — The tip was not disturbed because it appeared normal in the radio- gram. In the light of subsequent experience, the radiogram in this case would have indicated that operation might have been deferred. Case 3. A. Z., male, aged 55. Diagnosis : Subacute tuberculosis of left middle ear and mastoid. X-ray examination (two plates at different times) of left ear only, showed a very large pneumatic mastoid with hazy outlines of its cells. Radical opera- tion revealed pus and granulations in the middle ear and antrum, and showed serum in the mastoid cells, some of which extended behind the sinus. Fig 4. Tracing from a radiogram showing osteosclerosis of mastoid (left) and a defect (?) ini tegmen antri. (M) Sclerosed mastoid; (M F) middle fossa: (D) de- fect; (C) external auditory meatus; (J) mandible. RAXSOHOFF MEMORIAL VOLUME Fig. 5. Radiogram tracing of left mastoid region, showing osteosclerosis of mas- toid process*. (M) Middle ear; (M F) middle fossa; (S S) sigmoid groove: (L L) suture lines. Remarks. — Some of these cells might have been overlooked had they not been delineated in the radiogram. Case 4. H. X., male, aged 62. Diagnosis: Chronic suppurative otitis media in left ear with caries of the promontory: unhealed radical mastoid in the right ear. Radiogram (Fig. 4) of left mastoid region showed dense shadow of ostersclerosis, and a few cells, just indicated, in the antrum region. A small break was noted in the line of the middle fossa and a tentative diagnosis of a defect in the tegmen antri was made. Radiogram of the right ear showed large opening made by a previous operation. Ol'eration. — December 29, 1908. This revealed a dense sclerosed mastoid, large antrum tilled with pus and granulations, and a defect in the tegmen antri with the dura covered with granulation at this point. Subsequent History. — The patient died on the forty-first day after the operation. Postmortem revealed tuberculous lesions in apices of both lungs and a tuberculous caries of the right internal ear and pyramid. The temporal bone, showing defect over the antrum, was removed. Fig. 6. Tracing from a radiogram. Xormal mastoid. (M) Meatus; (M F) mid- dle fossa: (S S) sinus; (.C C) mastoid cells: (P F) posterior fossa: (L L) suture lines; (J) mandible; (O) orbit; (Z) zygoma. (Right mastoid region of Case 5.) Case 5. H. B., female, aged 4. Diagnosis: Chronic mastoiditis on the left: right ear normal. X-ray examination: An excellent picture of the left side showed a dense shadow of osteosclerosis and clear zone corresponding to the middle ear and antrum, the sinus being sharply outlined (Fig 5). The right mastoid shows normal diploetic bone and the sinus (Fig. 6). Operation January 11, 1909, showed a small fistula in the external auditory meatus leading into the antrum, which was filled with granulations ; the sinus was not uncovered. Remarks.— ThQTe is a striking contrast between the radiograms of the right and left mastoid regions. Case 6. F. M., male, aged 2Yi. Diagnosis: Acute otitis media with mastoiditis on the left. X-ray examination of the right side showed mastoid process of infantile type. The left shows the same in addition to the outlining of the posterior semi- circular canal (Fig. 7). Operation January 19, 1909, revealed softened bone about the mastoid antrura Page ni SAMUEL IGLAUER Fig. 7. Left mastoid region, showing posterior semicircular canal : (M) Meatus; (D) diploetic bone; (P F) posterior fossa; (O) orbit. Remarks. — The outlining of the semicircular canal on the one side and not on the other would indicate that the bone over the canal was softened. Case 7. J. R., male, aged 21. Diagnosis: Chronic suppuration in the right and left ear (of years' duration). X-ray examination (Fig. 8) of the right ear only (two pictures) showed osteosclerosis, absence of cells from the tip region and a rather forward lying sinus. The meatomastoid operation (February 3, 1909) uncovered a small deep-seated antrum with a few adjacent cells containing a few drops of pus; the sinus was not uncovered. Remarks. — The tip of the mastoid was not disturbed, since the skiagram showed that it was not involved. Ill addition to the above, live patients on whom ma.stoid operation had been performed were radiographed after operation, and the ;ippearance of Fig. 8. Tracing from radiogram: (M) Meatus; (I) antrum (?) ; (M F) middle fossa; (P) sclerosed mastoid process; (S) sigmoid groove; (Z) zygoma; (J) ascend- ing ramus of upper jaw. the operation cavity noted. One of these skiagrams taken several months after a Schwartze operation was especially interesting, since it showed that a number of cells had not been opened, and still the patient had made a perfect recovery. The number (four) of acute cases examined is too limited to permit of any definite conclusions being drawn. One of these came to operation as already described above. The second case, that of a little girl of 10, simu- lated mastoiditis. The Roentgen picture of the affected side showed a hazi- ness of the mastoid cells with clear cells on the sound side. The patient re- RAXSOHOPF MEMORIAL VOLUME covered without operation, and the radiogram taken six months after re- covery showed that the cells had regained their normal contour. The third case of acute otitis media showed similar clouding of the cells on the affected side. These two cases are interesting as confirming the con- tention of V. Troelsch* and of Politzer,' that the mastoid process is involved in most severe cases of acute middle-ear infection. The skiagram in the fourth case, which is too recent for complete description, shows a fistula leading into a large abscess cavity in the mastoid process. It appears prob- able that repeated X-ray examination in acute cases will give valuable infor- mation concerning the progress of the disease. CON'CLUSIOXS. ]n conclusion it may be stated: 1. The most satisfactory Roentgen pictures may be obtained in oblique profile of the temporal bone. 2. The internal anatomy of the temporal bone can be determined prior to operation, and the knowledge so obtained is a great aid to the surgeon. 3. Osteosclerosis of the mastoid secondary to chronic suppuration can usually be diagnosticated by radiography. 4. It is likely that defects in the limits of the temporal hone will appear in the radiogram. 5. Cases failing to heal after operation should be controlled by skiag- raphy, as this may reveal the seat of the trouble. 6. The value of the Roentgen examination in cases of acute mastoiditis remains to be determined. 6. Troelsch, A. von: Lehrbuch der Ohrenheilkundc. Lcipsic. 1881. pp. 291-410. 7. Politzer, A.: Ohrenheilkunde. 89.1. p. 417. THE STRUCTURE AND MECHANICS OF DEVELOPING CON- NECTIVE TISSUE.* Raphaf.i, Isaacs. Cincinnati. When the fluid part of blood is precipitated, the clot of fibrin has a well- developed structure of interlacing fibrils. The production of this definite .structure from a fluid suggests that fibrillar appearances elsewhere in the tissues may have a similar origin. Such fibrillar textures are seen in con- nective tissue, in basement membranes, in cement substance between cells, and in the neurogliar tissue of the nervous system. The present paper is ?. study of these structures and deals with the growth, consistency, and re- actions of connective tissue and cement substance. The conclusions point to the view that the so-called connective-tissue fibrils are artifacts, and that the cement substance and basement membranes are parts of a homogeneou-: intercellular jelly. The variation in precipitation pattern gives a histologi- cal basis for recognizing diflferent stages in the physiology of organs. NOMENCLATURE. In a histological section of "fixed" connective tissue, fine fibrils can he seen stretching between the cells (Fig. 1). These are called connective- tissue fibrils (Mall, '02) or cxoplasmic fibrils (Mall, '02; Flint. '04) or coUaginous fibrillae (Bell '09). In the central nervous system a somewhat similar group of fibrils are known as neuroglia fibrils or fibrillated endoplasni ( Hardesty, '04). The name white or collagen fibers is given to a group of highly refractive, homogeneous strands of tissue found in skin and tendon, as well as in other parts of organs. The yellow or elastic fibers are also definite large threads of tissue, found in many organs. This paper deals with the development of the white and yellow fibers, and also the intercellu- lar jelly, a homogeneous substance lying between the cells and fibers, and giving rise, according to this view, to artificial fibrils on fixation or dehydra- tion. MATERIALS AND METHODS. For the purpose of studying the structure and development of con- nective tissue, chick, ])ig, and human embryonic material of different ages was used, the fixation and staining being varied to study the effects under various conditions. Living tadpoles and embryos of the chick and pig and adult frogs were used for the study of fresh tissue. The experiments were conducted along two lines. The nature of the tissues was studied from the animal tissue, and experiments were carried out with colloid solutions of gelatin, egg albumin and fibrin, of known strength and composition, under • From the Anatomical Record. December, 1919. RANSOM OFF MEMORIAL VOLUME Fig. 1. Appearance of connectiv. micrograph. 55-mm. pig embryo. Bouin haemotoxvlin. rils ami fibrin clot in vessels. Photo- -Mallory's connective-tissue stain and iron controlled laboratory conditions. The technique in each case the discussion of the phenomena in question. given under I'.F.H.AVIOR OF CERTAIX COLLOIDS. In dealing with living tissues, we are studying substances in a colloid state. Some of the properties of protoplasm are properties of colloids. AV'hen we see protoplasm absorbing water or secreting it, we are naturally reminded of a similar behavior in such substances as gelatin, fibrin, or white of egg. In these substances we can, by using filtered solutions, free them from morphological structures. Yet on precipitation we can produce elaborate patterns (Hardy, '99: Butschli, '92) (Fig. 2, C). These substances, when in the jelly state, can give rise to structures, resembling fibers and fibrils, if they are put under pressure or stress. A gelatin jelly, on pressure, can be broken into many droplets of different sizes, which give rise to structures resembling fibers and other details of tissues. These structures round up into drops when pressure is released. The behavior of fresh connective tissue is much the same. W'lien compressed between cover-glasses under Page JIS RAPHAEL ISAACS i0 .0 e ^' r ^^.\ -?v 2 F Fig. 2. Corresponding areas of subcutaneous connective-tissue of a six-day chick, fixed with various sokitions and stained with Mallory's connective-tissue stain. A. Connective tissue extract fourteen-day chick (salt solution), filtered, pre- cipitated with Zenker's solution and stained with Mallory's connective-tissue stain. Camera-lucida drawing. B. Fixed in Bouin's solution. C. Egg albumin, filtered, and precipitated with Zenker's solution. Camera-lucida drawing. D. Fixed in Zenker's solution. E. Fixed in Van Gehuchten's solution. F. Fixed in absolute alcohol. Camera — lucida drawings. the niicroscope. we see many striicture.s, but release of pressure results in little gelatinous droplets with but little structure. Syneresis, the property of colloids, which give rise to the secretion of a fluid containing the substance of the colloid in a dilute state, must be taken into consideration when the colloids of the tissues are considered. This process takes place comparatively quickly when viewed under the misro- scope, and a few minutes make a definite change in the consistency, tough- ness, and refraction of the colloid studied. The colloids which tend to under- go irreversible changes, as white of egg, show this property to a marked degree, and the differences in appearance are striking. One does not ap- preciate what elaborate structures and quick changes can be produced in this way until the process is studied under a high magnification. The structures produced can be emphasized by stains. Many inorganic salts, when precipitated under the microscope, present "patterns" of interlacing fibrils, composed of strings of minute granules or cyrstals. Such pictures simulate the fibril patterns of colloidal proteins, and remind one of the delicate cytological structures often shown in fixed tissue. Page 21 RAXSOHOff MEMORIAL IXILUME THE INTERCELLULAR JELLY. The jelly-like nnture of young embryos is a matter of common experience with all who have handled young chicks or pigs. \Mien lifted up by any l^art, they elongate and tend to stretch. They have the consistency of thick mucus, and a very small force is required to tear oiT a part or cause com- jiression or strain. With increase of age. an increase of firmness is noted. For microscopical examination of the intercellular substance it is necessary to put small pieces in a hanging drop in a moist chamber or underneath a cover-glass on a slide, sealed with vaselin. no fluid of any kind being added. The temperature can be kept constant and evaporation can be avoided to a certain extent. However, the pulling and squeezing of the tissue in handling and cutting and the changes of tension when flattened against the cover-glass are factors to be considered in interpreting the re- sults. Under favorable conditions, observations may be taken on the tissue for a few minutes without much physical change. Maxinow ('06, p. 683) used a somewhat similar method, but at this technique did not show up certain cellular structures which he had expected, he emphasized these structures by producing a local oedema with physiological salt solution. Th-? results of such a procedure, however, require cautious interpretation, as the equilibrium of the intercellular colloids is easily disturbed, a process often encountred in the physiology and pathology of connective tissue. The subcutaneous tissue in a five-day chick reacts as a mass of jelly when touched. The tissue can be indented with a blunt needle, and the celh'. and substances around the point are bent. If a piece of tissue be "fixed" in this position, the position cells will show the results of the pressure, but the "connective tissue fibrils" will radiate in all directions, independently of the lines of force of the pressure. If they had been present in the living tissue, one would expect to see some results of compression, as the cells themselves show. In the living, the cells and the substance between them act as if they were a mass of the same consistency throughout, and the physiological unit for response to pulls and tension is the region afifected, not separate cells. When tissue is mounted as described, it becomes flattened against the cover-glass, and a narrow zone of a jelly-like colloidal substance, containing granules, forms the peripheral region. This jelly responds to a touch with a needle, much as does the tissue itself. On indenting one side, granules throughout the jelly move in response to the strain set up. The jelly is probably composed of intercellular substance — ^"tissue juice," lymph, and plasma. The intercellular colloid is more viscous than lymph, and does not run up into a capillary tube, as does the latter. Varying with the conditions, this jelly undergoes a change on standing from two to five minutes. The granules of various kinds begin to aggluti- nate around the outer edge of the jelly ring, and the peripheral zone be- comes stiflfer. A process re.sembling crystallization takes place, resulting in Page iiO RAPHAEL ISAACS the formation of a network from the masses of granules. The netvvorl; is microscopic, and under low ]50wer resembles a fuzzy mass with a ground- glass efifect. The basis is a fine matrix of fibrillae, made up of granules, but sometimes it is fairly homogeneous. It resembles connective-tissue fibri!.^ in appearance, taking the same stains — aniline blue, orange-G, and acid fuchsin. The behavior is similar to that of coagulating fibrin. Ranviev ('89) described a similar process as the normal method of formation of the large white fibers of the connective tissues. This process may be hastened by drying, heat, dehydrating, and coagu- lating fixatives. Formalin gas produces a fairly homogeneous fixation, but dehydrating destroys this efTect. The fibrils formed correspond closely to Baitsell's ('15) fibers, formed from the fibrin clot of cultures of chick tissue in vitro. He points out that "the transformation of the fibrin net results in the shrinkage of the clot. It also becomes very tough and resistant to injury." The process is hastened by mechanical manipulation of the clot with needles. This same phenomenon can be reproduced in filtered egg al- bumin, manipulation giving rise to the appearance of well-defined fibrils. The intercellular substance clots as if it had fibrin as its basis, but the varia- tion in staining and the consistency during life give the impression that some mucoid elements are present in addition. The jelly is more viscid than either plasma or lymph, and does not run, as do these fluids, but it can be made to undergo a gradual flowing. This holds true for all stages, from the embryonic to the adult tissue. As the peripheral fibrils form in our preparations, a watery fluid ac- cumulates just around the tissue itself and in the meshes of the fibrils. Th^s process, in efifect, is analogous to that of syneresis in colloid gels, and i^ familiar to us in the liquid accumulation over agar-agar or gelatin jelly. It takes place inde])endcntly of d.'ving eft'ects (Graham in M. Fischer, '15. ]). 240). As soon as this dilute liquid forms, the cells in contact with it swell, probably due to the increased acid content as the tissue dies or to the avail- ability of "free" water. This test, accompanied by the brighter a])iiearanc>- of the nuclei, which in the perfectly fresh tissue can be only indistinctl\ located, we use as signs of the beginning of the death process. The nucl'i appear brighter, either because they undergo a change of consistency and become more viscous or else because the cytoplasm becomes less dense, due to the absorption of water. When the term fresh tissue is used in thi; paper, it refers to the condition before the appearance of these changes. The blood corpuscles do not change shape for some time after this, and a|:- ])ear less sensiti\e than the embryonic tissue cells in this respect. However, as the changes take ])lace, the nuclei of the erythrocytes show ver}' clearl-,' in the chick material. The fact that blood plasma is relatively more dilute than the intercellular colloids proliably accounts for this difference of be- havior, and this factor should he taken into account in interpreting tissue cultures in which plasma is used. The preservation of the shajje of the blood corpuscles is no test for isotonicity as far as the tissues are concerned. Page ;.'.■/ R.-iXSOIWFP MEMORIAL VOLUME as the corpuscles do not change in salt solution in the presence of "free" water (not in colloid combination). The tissue cells under these circum- stances are affected immediately. In the fresh tissue itself (chick and pig embryos) the position of the cells can be made out fairly accurately. No free-flowing intercellular "tissue lymph" can be demonstrated. On tilting a slide containing a tissue mount, the intercellular substance remains. It does not run out under pressure, showing that most of the liquid is held in colloid combination. Sutflcient pressure, however, easily crushes the cells, and a considerable amount of liquid is liberated in this way. This liquid flows readily, differing from the intercellular colloid. The spaces, corresponding to the intercellular con- nective-tissue spaces of fixed tissue, are filled with a clear, homogeneous jelly- like substance, which, in the younger embryos, has the consistency ( not nec- essarily concentration) of a "wobbly" gelatin gel. The phenomenon of compression of this colloidal material is very in- structive, as we can easily reproduce some of the processes taking place in the developing embryo. A needle pushed into the tissue causes a response in all parts of the tissue, as seen by the movement of visible granules. It can be described best as the jarring of a colloid jelly. Cuts close up with but little evidence of separation, and the pathway of a needle withdrawn i^ apparently obliterated. If a piece of the tissue is suspended from the tip of a needle or forceps, the lower end rounds up, as does a drop of stringy mucus. If a freshly cut piece of tissue is placed on top of a second piece, and the two are killed and fixed in this position, with no other pressure than the weight of the tissue, it is found on sectioning that fibrils extend in places, without interruption from piece to piece (Fig. 3). This suggests that the fibrils are formed by the dehydrating or coagulating action of the fixatives from the homogeneous jelly. If, however, the bridging fibrils were merely pre-existing fibrils of one piece which have stuck to the other piece, then we would expect the fibril to be present throughout the gap be- tween the pieces of tissue. Fibrin would give a similar picture. The fibrils are present, however, only in places, presumably where the colloid has had time to ooze. Of course, air bubbles must be excluded. Fibrils in sections, then, may stretch across between parts which in the living may have been in contact or separated by the intercellular jelly. Sections often show such pictures around the more solid organs, as the thyroid or thymus, and thev suggest that these organs evidently push into the connective tissue, which conforms to the new, irregular outline, by a flowing or oozing process, re- minding one of the tissue closing in on the pathway of a withdrawn needle. In compressed tissue, which is fixed and sectioned, the cells show the result of the pressure by their alignment — usually being flattened out, with their long axis perpendicular to the direction of the pressure — but the fibrils of the section show no evidence of the stress. In living tadpoles Clark ('12) describes a delicate network of minute tibrillae between the cells. These, however, are not as numerous as the RAPHAEL ISAACS Fig. killed in ])iecL'S of tissue, which have heen allowed to t position. Photomicrograph. Mallory connecti\e-tissiie fibrils which the fixed tissue show. These fibrils, which are seen in the living, can l)e picked out from the connective-tissue fibrillae after the section \c, fixed, and suggest the branching cytoplasmic processes of stellate cells. When a precipitating agent, as mercuric chloride, acts on colloidal solu- tions, as of egg albumin, of different strengths, the substance is precipitated in greater bulk from the more concentrated solution, and therefore leaves a denser, more closely packed mass. In the weaker solutions the mas.s originally is much less dense, but when it settles, the mass may appear as dense as that from the thicker solution. However, in the weaker solutions it will be noted that the supernatant solution is often cloudy, turbid, or opalescent with a fine precipitate which does not tend to settle out. In the stronger solutions, this may be carried down with the rest of the flocculent precipitate, or else in the stronger solutions, the precipitated granules are larger. A. Fischer ('99) notes that the thinner the solution of a colloid, the smaller the granules precipitated with reagents. If, then, a weaker, but not necessarily a less viscid solution of a colloid will leave less precipitate than a more concentrated one when thrown down, then the strength of colloidal solutions in tissues can be judged by the amoutit of residue they leave in fixed sections. The very young etiibryos show a much more semi-fluid condition when picked up than the older ones. Schafer ('12, p. 116) points out that the albuminous substances of the cell interstices of very young embryos later acquire a muco-albuminous char- acter, and the tissue assumes a jelly-like consistency. Triepel ('11) describes RAXSOHUFF MEMORIAL VOLUME a corresponding series for fixed sections, a fine network in young stages, which becomes coarser as the embryo grows older. On pressure on the subcutaneous connective tissues taken from a four- to seven-day chick mounted between a cover-glass and slide and sealed with \aselin. pieces can be made to separate off from the central mass, just as ])ieces can be broken ofif of a "wobbly" gelatin gel. If the microscope it tilted, these pieces will slip down, accommodating their outline to the sur- rounding obstacles. Such a mass, on flowing between two fixed particles (as pieces of glass), will be drawn into a very narrow thread as a string of ropy mucus. On flowing through, it is reconstituted or regathered as a mass as soon as an open space is reached (Fig. 4). The ease with which a group of cells separate and regather with little or no trace of their experi- ence, even on fixation, suggests that the syncytial appearance of young con- nective-tissue cells is a temporary, apparent union of the cells, easily changed by the conditions of the environment. It is not impossible to im- agine a similar process taking place on handling and fixing an embryo. Subcutaneous tissue Separation of cells Kig. 4. Tissue from a four-day chick allowed to slip between two pieces of glass, while inounted under a cover-glass. After the entire mass squeezed through, one cell at a time, fixation shows the fibrils intact between all the cells. Camera-lucida drawings. Lymphatic vessels and capillaries may be compressed, cell masses pushed out of their places, adhesions formed, all without leaving evidence of their original condition. This may be one way of interpreting the isolated en- dothelial-lined spaces and lymphatic anlagen described by Huntington ('10). McCIure ('10). and Kampmeier ('12). The last points out (p. 430) thai "histologically all incipient lynijihatic anlagen . . . are decidedly dif- ferent from either an active vein or a mature lymphatic. They lack definition and possess vague and undififerentiated outlines ; for the cells of their walls are not arranged in that end-to-end fashion so characteristic of vascular endothelia. Instead, many instances were observed under strong magnifica- tion where the tissue cells in their longest diameter stand perpendicular to Page -'-'} RAPHAEL ISAACS the periphery of the anlagen and project far out into the kimen with their cytoplasmic filaments." Kampmeier interprets this condition as being brought about by the addition or fusion of contiguous spaces. However, these regions may have been continuous, and the apparent interruptions may have resulted from adhesions al the time nf fixation. The adhesive process may also describe the segmentation of the "retro- gressive venous channels" of different authors, in which the lumen of a vessel is interrupted by solid cell masses. The value of Kampmeier's ob- servation (p. 433) that more delicate fibrils lie in the pathway of future lymphatics is evident, as it is proljable that these represent regions of less concentration than the surrounding tissue, less precipitate having been left. Kainpmeier (p. 451) further observes that "the elongation of lymphatic spaces and their fusion finally into a continuous channel, as well as a growth of their cavities in diameter is accomplished by the .same process which gave origin to them, namely, by the disintegration of tissue fibrils and the con- centric addition of .spaces." The coagulated fibrils, however, as sections show, wall off spaces in one dimension only, while in the living condition the intercellular colloid is continuous throughout the region. The correspond- ence of the ages of the individual embryos in which these conditions are found indicates that the intercellular substance in certain definite plac.-s is in the same physiological condition. Inasmuch as we can conclude from Kampmeier's observations that less dense regions form in the tissue and inasrnuch as we have considered the mechanism by which adhesions can be brought about, we have a physiologi- cal basis for the distribution of growing lymphatics and blood-vessels. As the free-flowing blood and lymph are confined to vessels, walled in by en- dothelium, the growing ends of the proliferating capillaries probably follow the lines of least resistance and therefore take the less dense pathway through the tis.sues. It is conceivable that regions where oxidation of acid. or their neutralization becomes deficient, the tissue would absorb more water and eventually almost liquefy, allowing a growing capillary free access, and thus automatically establishing a better circulation for that part. The regions of finer fibrils in the iiatlnvay of growing capillaries strongly suggest this view. In fixed tissue it is not possible to make observations on the small changes in hydrogen ion concentrtion necessary to influence the tissues. These changes may be exceedingly small, as shown by their influence on the secreting mechanism of excised kidneys (Isaacs, '17). Furthermore, "young" capillaries of the blood and lymph system do not show concentric layers of connective tissue around them as do the larger vessels which have increased their size in situ, or more solid organs as the thyroid, thymus, ■ir the salivary glands in the embryo, showing that little or no compression took place as the capillary grew in (Figs. 1 and 5). This holds true, even though we take into account the contraction on fixation. RAXSOIIOI-'I- MEMORIAL VOLUME THE FIBER PRODUCING CELLS. Of cellular constituents, the spindle shape is apparently the more stable form. The multipolar forms can be considered as response forms caused hv the conditions of the environment at any given moment. Ferguson ("12) and Clark ('12) have described the changes of shape of living connective- tissue cells, and their work points to the independent movement of these cells. Ferguson (p. 134) notes a change from round to stellate and stellate to round. In chick tissue, however, most of the cells take a short spindle form when surrounding tension and pressure is released. Ferguson's (p. 135) observation, that "the shape of tlie cell (stellate type) is undoubtedh influenced to some extent by its surroundings, and the duration of a par- ticular stellate, spindle or lamellar shape may in some cases be thus de- termined," can be demonstrated by \arying the pressure on the cover-glass in a tissue mount. His statement that "the general trend from round t.) Fibr n .. ( /^J\ Connect ve ""T"' .fcf t ' - y-i. i S/ ^ Fig. 5. Connective-tissue tibrils and fibrin in subcutaneous tissue of 55-inm. pig embryo. Fixed in Bouin. Stained in Mallory's connective-tissue stain and iron haematoxylin. Camera-lucida drawing. Stellate and from stellate to spindle is inevitable" is significant in indicating the changes of tension in the growing embryo. Rous and Jones f'16) de- scribe a series of changes taking place in cells freed from connective tissue by digestion with 3 per cent trypsin solution. Under these conditions, the cells tend to become spherical. In our preparation we can also make the cells assume a more spherical form if any solution is added which contains more free water than the normal environment of the cells. This does take place of itself as soon as the water of syneresis forms in our preparations, as described before. From the fact that in fresh mounts most of the multipolar or stellate cells on release from the tissue, before any stiffening takes place, assume Page -'-'« RAPHAEL ISAACS the spindle forms, we can assume that the factors affecting the shape of these cells are the pulls and pushes affecting the region. Change in shape of a cell thus accompanies a change in surroundings. A comparison of the more compact mesenchymal tissue (greater number of nuclei per unit area) of a 10-mm. stage with that of a 30-mm. pig shows the latter to be looser, in spite of the fact that the growing internal organs take up increased space and taking into consideration the contraction of the outer layers on fixin;;. Evidently the tension changes as the embryo grows. Clark ('12. p. 366) docs not conclude that the change in position of individual cells can be accounted for only on a basis of general growth. When a piece of tissue is pushed with a needle under the misroscope, the mucoid nature of the mass causes it to react as a whole, each cell being affected by the surrounding push just as much as the surrounding colloid. However, the cells are in a temporary stage of unstable equilibrium, and gradually work their way in the colloid until they have reached the most stable position for the new set of conditions. .\ demonstration of this process is seen in the descent of a piece of lead through a gelatin gel, or the conditions may be better illustrated with a watch spring enibedd-ed in gelatin of such a .strength that the two bend together. After bending, the spring will eventually straighten itself by workin;,' through the gelatin. This process, which is really diapedesis, is probably the mechanism by which tissues are shaped in response to pressure or tension stimuli. As the tissue grows older, it becomes denser, the jelly becoming thicker, and response to pulls and pushes by permanent change in form less marked, because the cells have less freedom in the thicker jelly. Kaneko ('04) de scribes this in granulation tissue, is which the direction of the fibers which may be formed is influenced by the direction of stresses or pulls, while this response is lost in fully formed connective tissue. It is of course a matter of general experience that embryos shrink in fixing or during the dehydration process. While this accounts for some of the compression of layers immediately underlying the skin and around the more solid organs, some is no doubt due to the fact that organs, as the glands, in their growth, glide into the connective-tissue jelly, which is first compressed and then readjusted to the new conditions. Sections often show the connective tissue compressed, yet separated by spaces from such organs as the salivary glands or thyroid, the space being bridged here and there by fibrils. This can be interpreted as indicating that there is no firmer union between the connective tissue and the gland other than that of the gener;il stickiness, due to the viscous intercellular substance. The relation of d gland to the surrounding connective tissue may be illustrated with gelatin solutions. A strip of a 4 per cent gelatin gel is immersed in a 2 per cent gelatin sol. and the latter allowed to gel, or it may be treated with a fixative. It will be found that tlie fir.st strip, which is optically well marked off from its surroundings, retains its identity, and on being pulled out, retains some Page -vr RAXSOHOFF MEMORIAL VOLUME of the weaker gelatin sticking to it. However, this can be wiped off and the two separated. This expresses the relation of a growing gland to the con- nective tissue. The ease with which embryonic connective-tissue cells (four-day chick) can be separated in the fresh condition indicates that their syncytial appear- ance is due to adhesion. Ferguson ('12) has observed the union of cell processes in living fundulus embryos, and Clark ('12) has mapped out their successive space relations in growing tadpoles. Under such circumstances, fibrils, if present, would either anchor the cells or else leave a visible trail of the ceil passage. However, in sections they surround the cells on all sides, with no appearance as the tail of a cement, that we would expect under the circumstances. On killing the tissue, contraction and great shrink- age often results in the separation of the connective-tissue cells, so that many investigators, not being able to trace the connection from one cell to another, have concluded that the cells fade out into the fibrils. THK "KIBRll.S" .\X1) FIBER FOKMATIOX. That the fibrils are artificial coagulation products may be inferred from the dit^'erence in delicacy of the pattern with different fixatives (Fig. 2, B, D, E, F). Triei^cl ("11) notes this variation with the fixatives in studying connective-tissue fibrils and that of the coagulum in the blood-vessels in a given region in an embryo is somewhat the same. Triepel ('11) calls at- tention to the remarkable constancy of the pattern and its characteristic formation. This is of course natural, if the fibrillae are products precipi- tated by the fixatives. However, he attributes the different sizes of the fibrillar details to different amounts of shrinkage caused by different fixa- tives in preexistent fibrils. Hansen ("99) recognizes "pseudofibrillae" of cartilage as artifacts ("alcohol fibers" of Solger), but does not apply the principle to connective-tissue fibrils. The fibrils take a golden-yellow color with orange-G, a light jiink with acid fuchsin, and a blue with the aniline blue in Mallory's connective-tissue stain. With the latter, the bodies of the connective-tissue cells stain pink or orange-pink. (Fergu.son ('11) describes the collagenous fibrils as taking a golden-brown color with Bielschowsky's silver method. From the foregoing description of the origin of the fibrils as precipitation products, we car. account for the variation in results with silver-impregnation methods. The fibrils cannot be demonstrated in the fresh mount with any of the above stains nor with the so-called vital stains, until subsequent changes, possibly dehydration, lead to fibril formation. The more solid elements of the tissue, including the white fibrous, the yellow elastic and the precartilage tissue, are formed from the intercellular jelly by the depostion of more material, making the jelly more concentrated, thus leaving more precipitate in fixed sections. The gelation and stiffening of the white and elastic fibers can be easily followed in the fresh subcu- RAPHAEL ISAACS taneous tissue and tendons of the chick. Fresh preparations are mounted between the slide and cover, sealed, and examined immediately. Twelve- day chicks and those just hatched, illustrate the stages. While one watches through the microscope, slight pressure on the cover will serve to separate pieces of tissue. Elongated strands of tissue, stretching from piece to piece, may be seen, with occasional spindle-shaped swellings. Analysis shows that these swellings represent connective-tissue cells, adhering to a stifif, jelly- like strand of the intercellular substances. On further separation, the strand apparently elongates. The fiber is very sticky at this stage. The older stages show that the connective-tissue cells are adhering closely to a well-formed fiber, and can be dragged along the fibers when tension is put upon them. The fiber is formed of the jelly between the cells, and the increase in tough- ness from a viscid state to a well-formed fiber is shown by its changes of ex- tensibility and consistency in the fresh and the varying intensity of the Fibers in fresii tissue Fig. 6. Appearance of libers in a si.\teen-day chick, when flattened under a covei' glass. Successive ages are shown (A) before and (B) after fixing. Camera-lucid; drawings. staining reactions in the fixed tissue. In the early stages, a well-formed young fiber can assume the appearance of a thick network, if it is treated with a coagulating or dehydrating fluid (Fig. 6). In the latter stages the jelly becomes thick enough, so that the holes remain when cells or muscle fibers are pulled out in manipulating the tissue. The sections indicate a progressive increase in concentration due to deposition of more material, i fact shown by the increase in the amount of intercellular precipitate in sec- tions. The fibers are first laid down close together in sheets or ribbons and separate into the familiar strands only after the expansion of the surround- ing areas. Fixation, of course, separates them by shrinkage. RA.VSOHOFF MEMORIAL VOLUME The speed of decolorization after staining is a factor in considering rela- tive densities. The small fibrils lose their stain sooner than the larger, and the white fibers last of all. A. Fisher ('99) and Mann ('02). however, suggest that the greater relative surface of small particles over larger ones, in comparison to their volume, allows greater space for washing out of the stain. No fibrils can be demonstrated in the early or later stages, nor doei jaiiis green, methylene blue, or neutral red show their presence. The edema set up by the use of aqueous solutions of these salts may be temporarily avoided by dusting a few grains of the powdered stain on the tissue. Tlie diffusion of the stain brings about the result desired from the aqueous so- lution by emphasizing the difference of refraction of the different constitu- ents. As different authors have pointed out, the vital stains of this type act only on tissue which has already begun to die. Granules may dissolve som. of the stain without killing the cell, however. Paramoecium, in which the posterior end is dead and consequently stained deep pink with neutral red. still retain their power of movement. Fundulus eggs can be grown in toxic solutions of substances, often, however, with the production of abnormalities. The continuation of one or more of the vital processes of a cell cannot be considered as a test of the normality, so that results with vital stains belong to the observations on experimental tissue, not necessarily normal. The cells are probably the active agents in influencing the deposition of the material. The modern simile of an assembling and distributing plant probably describes the function of the cells in handling the materials in fiber formation. The movement and migration of the cells probably afifect the distribution of the fibers and result in forming strands of the fibers, instead of one mass. The subsequent pulls and movements of the part as a whole cause the strands to glide over one another, and this is probably a second factor in the isolation of fibers. The appearance of fibers can thus be simu- lated in a gelatin or fibrin gel. There is some evidence to lead one to think that the cells are definitely polarized with respect to fiber-producing regioi'S, thus accounting for the fact that some regions remain more jelly-like while neighboring regions around the same cell stiffen. The cell in profile is flat- tened on the fiber side, but convex on the jelly side. Optical effects may be obtained with different concentrations of gelatin, giving the same contrast relations that are found in fresh tissues. If cubes of water-soaked gelatin of the same size are treated with dehydrating or hydrating agents of different strength (grades of alcohol, commercial forma- lin, \'an Gehuchten's alcohol-acetic-chloroform, or corrosive sublimate), blocks of varying density are obtained. The greater the density, in this case, the greater the refractiveness (Isaacs, '16). In other words, the greater the density of a colloid of this type in the tissue, the greater its refractiveness and the lighter it appears when in focus under the misroscope. It is for this reason that the cell nuclei and fibrils as well as other elements appear clearer when the preparation is allowed to stand and undergo coagulation and dehydration changes. The change is a real one, and is not merely due. Page 230 RAPHAEL ISAACS as has often been suggested, to the eye becoming accustomed to the prepara- tion. The suggestion naturally follows that the fibrils may have been present as slightly more concentrated areas in the interstitial connective substance and escape detection while observed in the fresh tissue. Maxinow ('06) de- scribes the ground substance as homogeneous, with granules which prob- ably represent a network. Danchakofif ('08 j considers that the spaces left in sections are due to extration or dissolving out of the intercellular sub- stance. While considering the action of reagents as accounting for some granular deposits, Danchakofif describes the fibrils as cell processes. How- ever, the precipitating action of reagents can be seen under the microscope by applying them with a delicate pipette to the undersurface of a hanging- drop preparation, thus avoiding the danger of "washing out." The action is seen to be one of condensation and precipitation of the dissolved material, leaving the fluid part in the meshes of the resulting granular coagulum. The results can be checked up with stains. Hober ('14) states that structures produced in gelatin by alcohol are not preformed, but are produced on dehydration. In order to see if the fibrillae were performed or were artifacts, the tissue (skin, subcutaneous tissue. or muscle of a chick embryo) was pressed free from blood and lymph, and then irrigated with a potassium oxalate salt solution (Ringer's solution with potassium oxalate substituted for the calcium chloride, an empirical solution) and the solution filtered. A similar solution can be made by allowing con- nective tissue to stand overnight in a little Ringer's solution. Treating u drop of this solution, after filtering, with absolute alcohol or Zenker's so- lution on a slide, a complete network, resembling that of the tissue fibriU, was obtained, and it took the fibrillar stains (Fig. 2. A). Extracts from most tissues can be precipitated in the same way, giving fibrillar structures char- acteristic of each tissue. The fact that a complete network was obtained in this case would seem to indicate that the fibrillar network was an artificial precipitation product. Fixation of the washed tissue shows a decrease in the number of fibrils. The substance which was filtered evidently contained material from the more fluid intercellular substance. It is to be expected that this contained the same serum albumin, serum globulin, and fibrinogen that we normally find in the blood and lymph, and this in the end is probably the key to the network formation between the connective-tissue cells. The presence of some mucin-like substance alters the staining reaction somewhat and enables us to differentiate it from pure lymph coagulum. A similar substance and a similar network may be encountered in any tissue. The net- work bears the same relation to the intercellular jelly as the crystal colonv bears to the solution from which it develops and is specific for each of the different colloids under the same conditions. Fleming ('97) and others maintained that the fibers were transformations of the eel protoplasm, Meves ('10) specifying their orgin from chondrioconta at the cell surface. RANSOHOFF MEMORIAL VOLUME FRAMEWORK OF ORGAN'S. The digestion method of demonstrating fibrils, as applied by !\Iall ('92') and others, takes advantage of the fact that the fibrils apparently resist pancreatic digestion in alkaline solution. Mall ('02) finds that unfixed, frozen sections which are digested are difficult to stain in any satisfactory way, due to mechanical difficulties. He obtained a better picture in alcohol - fixed tissue. Flint ('04) suggests the use of alcohol-chloroform-acetic acid, sublimate acetic, or alcohol alone to show the "fibrillar framework" of organs by pancreatic digestion. Formalin cannot be used for this purpose. It will be noticed that those reagents best suited for this demonstration coagulate the homogeneous connective-tissue colloids under the microscope into the hard definite connective-tissue fibrils. Zenker's solution, while showing the fibrils, presents secondary difficulties which bar its use in digestion work. Sublimate solutions and chromium salts cannot be used advantageously in studying connective tissue, as the coagu.ated colloids fringe the cells with fibrils, thereby covering up many details. Fresh tissues exposed to several changes of an alkaline solution of pan- creatin for varying lengths of time (from days to weeks) without any preservative, but conducted under aseptic conditions, do not show the fibrillae when mounted under the microscope. Instead, we have a uniform jelly between the white fibers and the spaces occupied by the cells. The fibrillae, however, can be made to appear by dehydrating or coagulating agents. Thi; enables us to interpret Mall's ('02) results when he finds that the digestion method "causes the sections, if fresh, to become a swollen and slimy mass in which the delicate fibrils can be seen after it is treated with picric acid." Picric acid precipitates the fibrils from solution. A consideration of the following test-tube experiments may be helpful in this connection. If fresh albumin is digested in an alkaline solution of pancreatin, a clear solution re- sults. The addition of alcohol or sublimate acetic results in a flocculent precipitate (peptones). Therefore, if any product of digestion remain in the homogeneous jelly resulting from digestion, we can have just as com- plete a network formed as if no digestion took place. Posner and Gie.s ('04) point out that the "connective-tissue mucoids are readily digested by trypsin in alkaline solution." If the washing is complete enough to remove the products of digestion, then the tissue falls to pieces and the results are considered "unsatisfactory." The unreliability of digestion methods is a part of the experience of all who have used them. This would indicate the possibility that the fibrillar details in the framework of organs and base- ment membranes may be products of fixation. Mall ('92), Flint ('04), and Moody ('10), among others, give excellent descriptions of such digestion preparations, which, if considered from the point of view of coagulation products, indicate something of the distribution of the iiUercellular colloid. Page 2SZ RAPHAEL ISAACS NEUROGLIA AND THE INTERCELLULAR TELLY OF THE NERVOUS SYSTEM. The jelly-like nature of fresh nervous tissue, as the cerebral hemispheres of the adult frog or its medulla, is a constant characteristjc. This tissue when mounted fresh between a slide and cover and sealed shows a field of cells, nuclei, and nerve fibers imbedded in a clear homogeneous jelly. By varying the pressure, difTerent details can be brought out. If some alcohol is allowed to run under the cover, the picture changes entirely. A heavy groundwork of very delicate fibrils develop both in the tissue and in the expressed jelly surrounding it. The nerve fibers often act as bases around which and from which the fibrils radiate. Van Gehucten's fluid gives an equally heavy crop of fibrils. The presence of different structures, as capil- laries, active ciliated cells, and nerve fibers, serve often to give a clue as to just what part of the brain wall we are studying. Hardesty ('04) points out that the development of the neuroglia fibers is a process of transformation of fibrillated areas. The deeply stained fibers in the exoplasm of the syncytium of his sections are seemingly derived from a condensation of the less deeply staining substance. However, a study of the fresh tissue leads to the conclusion that this described for- mation is really the result of precipitating the successive stages with thf. fixative. The increase in concentration and density brought about by ad- dition and deposition of more material to the jelly gives us a basis for varia- tions in the pictures obtained in successive stages. Coagulation or fixation, then, would leave a more compact mass where the fibers are, but a delicate network ("fine threads of the spongioplasmic network" (p. 262) in the less concentrated parts. This work corroborated Weigert's and Hardesty's (p. 257) conclusion that "the fibers cannot be regarded in any sense as out- growths of the cells," but, on the other hand, it indicates that we are dealing with more or less concentrated colloids of the homogeneous intercellular substance and that the fibrillated appearance of the so-called exoplasm is a fixation product. Holmgren ('04) and later Ross ('15) have described prolongations of cytoplasmic processes of glia cells, which appear in section to run into the "trophospongia" of the nerve cells. These apparent "non- nervous partitions of capsular processes continuous with the glia cell" are in reality the remains of the intercellular jelly which when coagulated by the fixative or in post-mortem processes appear to be fine protoplasmic fibrillae continuous with the glia cells on the one hand and the tro]ihospongia on the other. SU.\nLARY AND CONCLUSIONS The intercellular jelly of embryonic and adult tissue is structurallv homogeneous and contains no network of fibrils. The evidence may b.- summoned up as follows : 1. Fibrils cannot be seen in the living intercellular substance. 2. Fixatives, drying, dehydration, or coagulating reagents are necessary to show the fibrillae. Page 2.M RANSOHOFF MEMORIAL VOLUME 3. In young embryos llie cells may he rearranged by manipulation of the tissue, but on fixation the fibrils are continuous. 4. The process of fibril formation can be followed under the micro scope. 5. The possibility of ■"wasliing out"' a non-coagulated colloid from tiie meshes of a network can be eliminated by fixing the tissues under the microscope. 6. The form and structure of the network varies with the fixative. 7. Cut pieces of tissue ])laced in contact and fixed show a cuntinuity of fibrils. 8. Intercellular jelly wasiied out and passed through a filter can be precipitated as a complete network with the ordinary fixatives. 9. Complete washing out of the intercellular jelly gives a fibrillar- free picture when the tissue is treated with fixatives, while the filtrate can be made to precipitate as a fibrillar network. 10. Digestion methods do not show the fibrils unless some step in the technique involves a coagulating or dehydrating process. 11. Complete and similar fibrillar networks can be obtained h\ the ac- tion of fixatives on pure solutions of gelatin, mucin, plasma, egg-albumni and other solutions. 12. While the density of the network increases with the age of the tissue, the process is reversed when ])ost-mortem digestion or acidosis is allowed to proceed. The state of the colloid at the time of fixation deter- mines the type of fibrils. 13. Cells may move freely in certain embryonic stages, and sections show no track left by the passing cell in among the fibrils. 14. In fixed and sectioned tissue the cells and their processes and fibers show by their alignment the evidence of pressure or pulls. The "fibrils." however, radiate in all directions unclianged and do not show stress lines. The consideration of connective tissue and neuroglia fibrillae as fixation artifacts is of aid in accounting for the following phenomena: 1. Movement of cells. Diajjedesis. (The jiathway is a structureless- jelly.) 2. Progressive increase in strength with age. from the jelly-likij younger embryos to the tougher adult tissues. 3. Non-ai)pearance of fibrillae in the living, with their ai»])earance in fixed tissue. 4. The variation in the fibril pattern when dift'erent fixatives are used. 5. The similarity of pattern of fibrin in the blood-\essels and fibrillae between the cells. 6. The similarity of many of the staining reactions of the fibrillae and fibrin. Those stains which stain the mucoid element serve to differentiate. 7. Accommodation of the connective tissue to the iiuading cells of growing organs. Payf m RAPHAEL ISAACS 8. The appearance of isolated, fluid-filled spaces lined by endothelium in the connective tissue. 9. \'ariation in the behavior of successive sections or "siiiiilarlv" treated pieces of tissue when subjected to pancreatic digestion. 10. "Superiority" of fi.xed tissue over fresh tissue for demonstrating "fibrillar structures of frameworks of organs'" Ijy means of digestion methods. 11. The variation of behavior of fibrils to Rielschowsky's silver method. 12. The appearance of fixed tissue of cells, much smaller than when alive, apparently fading out into fibrillae. 13. The clear-cut lines of separation when connective tissue shrinks away from the more solid cell masses on fixation, lea\'ing a few fibrillae bridging the gap. 14. The stickiness of living connective-tissue substance and connective- tissue cells. 15. The increase in density of the fibril network with age. The more concentrated a colloid, the thicker the network that is formefl on ]jrecipita- tion. 16. The varying observations on basement membranes. 17. The appearance of ribbon-like fibers in the fresh, which turn into a thick network of fibrils on fixation. 18. The appearance of neurogliar fibrillae ("cell i)rocesses"j extending into trophospongia of nerve cells. The pecipitation of the intercellular colloid is a simpler explanation. The fibers of adult tissues are formed by the thickening (concentration increase) of the colloid lying between the fibroblasts. The polarization ot the cells, their movement and the stress exerted on the growing tissue, all serve to give the adult white fibers their arrangement as strands in a bundle. This method of fiber formation enables us to understand the shrinkage which accompanies fibrosis in the tissues. If we accept the fact that a less dense colloid leaves lighter fibrils than a more concentrated one, then we have a means of telling the consistency of tissues when the fixed sections are studied. A physiological determinant is also supplied, directing the d's- tribution of new capillaries along the lines of least resistance. MTERATURE CITED. Caitse'l, 1915. The origin ai id str uctur( ; of a fibrous tissue which appears in liv in g dturi 1 of adult frog tissues. Jour. Exp. Med., vol. 21, p. 479. Bell, 1909. On the histogene sis of adipc >se tissue of t he ox. Am. Jour. Anat., vo' 1.9, p 1. 421 Biitschli, 1892. Mikroscopische Sh; Leipzig. Clark, E. R., 1912. Further obser vation s on living g rowing lymphatics: their reU ition 1 to th ^enchyme cells. Am. Tour. An; «.. vol. 1.?. p. 3(.0. l>.inchakoff, 1908. TIntersuch. jnBcn ilber die Fntwicklu iiK von Blut und Bindgewebe bei V ogeli A,-c :h. f. mikroscopische Anatomie ' Li. Ent vvickl Lingsmechanik, Bd. 73, S. 147. Ferguson, 1911. The applicat ion of the : 5ilver-inn)regna ition method of Bielschowsky to ret iicula Anat .. vol. 1.'. p. : !77. Ferguson, 1912. The behavio r and relat ion of living . connective-tissue cells in the fins c ,f fis embryos, with special reference to . the h.stog enesis of the collaginous or white fibers. Am. Joui An: it, vol. 13, p. 129. Fischer, A., 1899. Fixirung, Farb ung und Bau des Protoplasnia. Jena, S. lA-2(i Fischer, M. H., 1915. Oede. na an. rl Nephritis, 2nd e( 1., New York, p. 240. RANSOM OFF MEMORIAL VOLUME Fleniming, 1897. Quoted from Schafer: Text-book of Microscopic A naloiny. 11th ed.. N,;' York. 1912. Flint. 1904. The connective tissue of tlie salivary glands and pancre as with its devehipnien in the glandula submaxillaris. Johns Hopkins Hospital Reports, vol. 12, p. 8. Hansen. 1899. L'ber die Genese einiger Bindgewebsgrundsubstanzen. .\natomische .\nzeigcr •12-). Hardesty. 19C14. On the development and nature of neuroglia. Am. Jour. .Anat., vol. 3. p. J Hardy, 1899. On the structure of cell protoplasm. Jour, of Physiol., vol. 14, p. 187. Hober, 1914. Physikalische Chemie der Zelle und der Gewebe. Leipzig and Berlin, S. 313. Holmgren, 1904. t'ber die Tropospongien der Xervenzellen. .Anatomischer Anzeiger, Bd. Huntington, 1910. The phylogenetic relations of the lymphatic and blood-vascular systems vertebrates and the genetic principles of the development of the systematic lymphatic vessels in Isaacs, 1916. Properties of colloids in relation to tissue structure. Anat. Rec, vol. 10, p. 5 Isaacs, 1917. The reaction of the kidney colloids and its bearing on renal function. .■ Jour. Physiol., vol. 45, p. 71. Kampmeier, 1912. The development of the thoracic duct in the pig. .\m. Jour. .Knat.. vol. p. 430. Kaneko, 1904. Kiinstliche Erzeugung von Margines falciformes und .Arcus tendinei. .\rch ICntwicklungsm. Bd. 18, S. 317. 92. Reticulated velopment to the connective tissues from the co .\ra. Jour. Anat., vol. 1, p. 33 -Mann, "' ■ " Physiological histology, Oxford, p. 10<>. Maxinow, 1906. L'ber die Zellformen des Lockeren Bindgewebes. .•\rch. f. tomie, Bd. 67, S. 683. McClure, 1910. The extra-intimal theory and the development of the mesenteric lymphatics the domestic cat. .Anatomischer Amzciger, Bd. 37, S, 101. Meves, 1910. t'ber Structur Kntstehung der Bindgewebstibrille Anatomic, Bd. 71, S. 149. Moody, 1910. Some features of the histogenesis of the thyroid gland in the pig. Anat. Rec, vol. 4, p. 429. Posner and Gies, 1904. ,\ preliminary study of the dipestibility of connective tissue mucoids in pepsin-hydrochloric acid. .\m. Jour. Physiol., vol. 11, p. 350. Ranvier, 1889. Ouoted from Schafer: Text-book of microscopic anatomy, Uth ed.. Lond.ui. 1912, p. 117. Ross, 1915. The trophospongium of the nerve cell of the crayfish (Cambarus). Jour. Comp. Xeur., vol. 25, p. 523. Rous and Jones, 1916. A method for obtaining suspensions of living cells from the fixed tissues and for the plating-out of individual cells. Jour. Exp. Med., vol. 23, p. 549. Schafer, 1912. Text-book of microscopic anatomy, 11th ed., London, 1912, p. llo. Triepcl, 1911. Das Bindgewebe im Schwanz von Anurenlarvcn. Arch. f. Ent« icklungmckhanik. AN EXPERIiMENTAL INVESTIGATION OF CERTAIN FEAT- URES OF THE PHARMACOLOGICAL ACTION OF SALVARSAN.* r,y D. E. Jackson, Ph.D., M. D., and G. Raap, A. B., A.M. Cincinnati. In a series of experiments performed at the Hygienic Laboratory in Washington in the year 1918 it was shown by Jackson and Smith* that one of the most important and outstanding features of the acute symptoms •>:' poisoning following the intravenous injection of arsphenamine solutions in (logs consists in the production of a very marked and prolonged rise in the pulmonary blood pressure. This within itself would perhaps be sufficient to account for a part, if not for all, of the milder toxic symptoms which are occasionally produced clinically by the injection of arsphenamine. But aside from the pulmonary vascular changes, there remained the possibility that the dyspnea and marked respiratory disturbances which are frequently pres- ent during "nitrilnid crises" nf severe, acute arsphenamine intoxication might be due to, or associated with, a marked bronchial constriction. This poin.t was not investigated by Jackson and Smith, although at that time the pres- ence of some such factor as this was strongly suspected, particularly on ac- count of the analogy in action on the bronchioles which is often exhibited among metallic salts. In the present work we have carried out some pre- liminary experiments in order to determine whether or not any true bron- chial asthmatic action is produced by injections of arsphenamine. The solutions used by us have been made up from ."salvarsan" as jiro- duced by the H. A. Metz Laboratories in New York. Mr. Metz has very kindly supplied us with a quantity of "salvarsan" of lot No. H56. This was a particularly good batch as had been previously shown by laboratory tests and by extensive clinical use. Generally our solutions have been made up to 2 per cent, strength of salvarsan, and the amount of alkali used mi neutralizing the dihydrochloride salt has been sufficient to produce the disodium salt, and in most instances a further slight excess of alkali has been added. In a few cases we used mixtures of the mono- and di-sodium salts. Fresh solutions were always made up only a few minutes before thev- were injected into the animal. Figs. 1, 2, and 3 show at once the action which salvarsan has on the systemic blood pressure (lower tracing) and on the bronchial musculature. The lung tracings in these experiments were made by means of a special method^ in which air was intermittently aspirated from the chest cavity while the tracing was made by a tambour connected with the side tube of tho tracheal cannula. The dogs were pithed in each case. In tracing 1 it is seen •I-rom Tlif lumnal of Uibu.atory and Clinical Medicine. October, 19J0. •From the Jiepaitnient of PhannacoloRy of the University of Cincinnati Medical School Cin cinnati, Ohio. Page ,.'.;? RA.YSOHOFF MFJfORfAL VOLUME that 20 c. c. of 2 per cent, salvarsan solution injected into a dog weighin<< 8.5 kilos produced practically no effect at all on the bronchioles, either in the nature of contraction or dilatation. Fig. 2 shows a moderate contrac- tion of the bronchioles as indicated by the slight reduction in amplitude of the respiratory tracing. (It should be noted here that the pulmonary press- ure of this animal undoubtedly rose to a great height following the injection of the salvarsan.) Near the end of this tracing an injection of 4 c. c. of codeine sulpliate (20 milligrams) was made. This produced a marked con- traction of the bronchioles and was intended to be a check on the technic Paijc .'JS D. E. JACKSON AND G. RAAP SI i •i3 1^ r 1 1 X 1* ^#31 1^. E Figure 2. of the experiment in order to show that the apjiaratus, the lungs, etc., were all working proijerly. Fig. 3 is a similar experiment in which 20 c. c. of salvarsan caused a slight dilatation of the bronchioles. These experiments show that good preparations of salvarsan do not cause a marked contrac- tion of the bronchioles. But, on the other hand, they do not show that especially toxic preparations might not produce very serious results in this direction. Obviously this point should be investigated further, and with a much larger range of samples of arsphenamine than we have Iiad at our command in the present investigations. A number of intermediary cheniica! RANSOHOFF MEMORIAL VOLUME jiiiiiiijfiiiiiiiiiiiiiiiiiiiiiiiininHiip""""""'"""^ compounds produced in the manufacture of arsphenamine were exammed by Jackson and Smith, but it appeared that none of those examined at that time could be responsible for severe, acute symptoms following arsphenamme, injections. But in a later paper by Smith'' it was shown that another inter- mediary compound, namely amino-hydroxy-phenyl-arsenoxide. which is an oxidation product of arsphenamine, affected the pulmonary blood pressure in a manner quite comparable with that of a solution of arsphenamine of corresponding strength. "The arsenoxide content of arsphenamine varies Page iV) D. E. JACKSON AND G. RAAP As=0 NHo OH usually between 0.5 and 2 per cent. Occasionally a preparation is encoun- tered that contains as high as 5 per cent, arsenoxide (Dr. C. N. Myers, quoted by Smith ) and such a prcjiaration might very readily be highly toxic Figure 4. owing solely to its arseno.xide content." Jn a recent article by Schamberg, Kolmer and Raiziss* the jirescnce in some arsphenamine and neoarsphen- amine preparations uf an unidentified toxic substance designated by them RANSOHOFP MEMORIAL VOLUME as "X" has been emphasized. And Stokes and Busman^ have reported toxic reactions following injections of arsphenamine through a ^^^t^'" ^rand of so-called pure gum rubber tubing when this is new, but not after the tubmg has been used for a short while. It is obvious that such factors as these might possibly cause a severe, or even fatal, bronchoconstrict.on m very susceptible patients, when any such constriction was complicated by th. lll ^iiiiiiiiiiiii liiiiiiiiiiiiiHillllliMIIM""'''"''"'' simultaneous presence of a great rise in the pulmonary artena pressure Unfortunately it will require many more expermients before all such ob sou mi phenomena as these can be fully investigated. But the present ex- perL'nt's have been sufficient to show that any dangerous b-ncoconstr.c- tion is not to be feared with the proper use of prst-class prcpa,aUons o. arsphenamine. (See also Hanzlik and Karsner^j Page IVi-i D. E. JACKSON AND G. RAAP Bearing in mind the evident rise in pulmonary arterial pressure after arsphenamine injections, as first demonstrated by Jackson and Smith/ and which was further investigated by Smith'* alone, we have attempted in th^ present work to investigate further certain features of this important reac- tion. We have accordingly devised a very sensitive method for detecting verv minute changes in the pulmonary pressure. The arrangement of the iiiiiiiiiiiiiiiiiiiiiii iiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiitiiiiiiiiiniii»iii»iiii""iiii'ii»"imi imiiii Figure 6. apparatus as used by us is diagrammatically illustrated in Fig. 4. In this illustration it will be seen that a cannula tied into the left pulmonary artery was connected with a manometer by rubber tubing. The chest was opened widely and artificial respiration was maintained throughout the experiment. Ether was administered by means of a special sight-feed device" which has Page :.",.; RAXSOHOFF MEMORIAL VOLUME been described by us elsewliere. The manometer and the rubber tubing con- necting witli tlie puhnonary artery were all filled with normal salt solution (0.8 per cent, sodium chloride in water). This solution has worked very well for us, and clotting has been very much less troublesome than was the case when we used sodium citrate solution. This latter is very poisonous and easily stops the heart if a small amount gets back into the right ven- tricle. Sodium chloride solution does not afifect the heart. The top of the distal limb of the manometer was connected by rubber tubing to a burette of 50 c.c. capacity. The salt solution reached only a little way up in the burette, the upper part of which contained air and was connected by means of glass and rubber tubing to a tambour having a bowl about two inches in diameter. The tambour was very sensitive and thus readily recorded on the drum very minute changes in the pulmonary pressure. Carotid pressure was recorded in the usual manner with a mercury manometer. Fig. 5 shows the results in two dififerent dogs of injections of salvarsan solution, as recorded from the pulmonary (upper) and carotid (lower) arteries. It will be seen that the pulmonary pressure rose abruptly to a great height and that it did not fall until the carotid pressure reached a very low level. In the left hand tracing only 8 c.c. in all was injected into a small dog, yet this killed the animal. In the right hand tracing 20 c.c. of solution was fatal. Fig. 6 shows a jirofound and lasting rise in pulmonary pressure follow- ing injection of 20 c.c. of 2 per cent, salvarsan solution. It will be noted here that the carotid pressure remained at almost the normal height for a considerable time after the injection of the drug, which was carried out rapidly. And again the pulmonary pressure remained very high until the heart had reached an extremely weakened condition. From Figs. 5 and 6 it will be seen that sudden intravenous injections of .salvarsan produce their chief circulatory results primarily in the limgs. ■From a clinical standpoint it is interesting to speculate as to what symptoms such an action as this might produce in the patient. And Fig. 6 shows further that an ordinary blood pressure determination as recorded from the arm might ])rove very deceptive so far as showing the real condition of the entire circulatory system was concerned. For here the general systolic pressure had fallen only a few millimeters at a time when the pulmonary pressure had risen to an enormous height. It will be noted, of course, that the dose and rate of injection here considerably exceeded that applying clin- ically. We have accordingly attempted to get some comparative insight into the matter by giving very small, consecutive injections as shown in Fig. 7. In this case 1 c.c. was injected and then, after an interval, a further 1 c.c. etc., was given. In this manner we are able to observe the immediate results following each separate small dose. It is seen that 1 c.c. causes a very con- siderable rise in pulmonary pressure. The second 1 c.c. dose still further increases this rise, as does each of the succeeding injections. And it will D. E. JACKSON AND G. RAAP be seen that the systemic pressure actually rose following the first injection. Five injections of 1 c.c. each and one injection of 3 c.c. (8 c.c. in all) finally brought the pulmonary pressure almost to the limit of its capacity to rise. And this process represented a duration of some minutes. Figs. 5, 6 and 7 all well illustrate a peculiar phenomenon which appears to be always present in experiments involving the rapid injection of salvar- san solutions. It will be noted that in each of these tracings the pulmonary tambour at the very beginning of the record exhibited marked excursions up and down. These excursions resulted from the respn-atory movements of the lungs. The corresponding excursions can also be seen in the mer- cury manometer tracing from the carotid pressure. The speed of the drum was too slow here to show the blood pressure movements following each individual beat of the heart. But immediately after the injection of the drug the pulmonary pressure started to rise. At the same time the ampli- tude of the respiratory excursions of the tambour began to decrease, and as soon as a very high altitude was reached by the pressure tlie respiratory Page 21,5 RANSOHOFF MEKWRIALJ^VLUME_ excursions were reduced to a minimum or disappeared altogether. But du - neall this period the respiratory inflation and deflation of U.e ungs re- main d consLt. for this was carried out by means of an art.fic.al resp.ra- doTmachine. Now let us ask. What is the cause of th,s pecuhar change "he pulmonary blood pressure as reflected from the respiratory excur- sionso? the lungs? For we have noted above that but httle change was produced in the bronchial musculature by the salvarsan. Figure 8. Fig 8 probably illustrates a point having a bearing on this subject. In this tracing it is seen that three small iniections of 2 -,.-f P™^"^ .^ marked rise in the pulmonary pressure but had only a shght e^ect on he carotid pressure. Following these, however, an mject.on of /. ex. of adrena- line (1-10,000) was given and this raised the carotid pressure but marked^ lowered the pulmonary pressure. At the same time there was a shght tendency for the amplitude of the respiratory movements of the pulmonary tambour to increase, that is, to return toward the normal agam. But as the Page 2!fi D. E. JACKSON AND G. RAAP effects of the adrenaline wore off the respiratory excursions of the tambour again became reduced. This same point is again illustrated, perhaps more markedly, in Fig. 9. This peculiar and unexpected action of adrenaline calls to mind at once the various clinical recommendations which have been made by Milian,^ Beeson," and others regarding the use of adrenaline in cases of severe arsphenamine poisoning. And the relation which adrenaline bears to the spasmodic contraction of the bronchioles in acute anaphylaxis Figure 9. also reminds one of the various anaphylactic hypotheses by which different writers have attempted to explain the cause of arsphenamine poisoning. We have not been able to prove, however, that the phenomena which we have noted here as being produced by adrenaline in cases of experimental acute salvarsan poisoning bear any direct relation to the clinical results which have been described as being produced by adrenaline injections in some cases of arsphenamine poisoning. On the other hand, the apparent improvement Page 2J,1 RANSOHOFF MFMORIAL VO LUME and lowering of the pulmonary pressure would undoubtedly be ot beneht u, these cases We strongly suspect that the lowering of the pulmonary pres- sure here was due to a mechanical shifting of the blood from the venous ,0 the arterial side of the circulatory system. This would result from con- traction of the arterioles. The direct action of adrenaline on the hear would also tend to m^prove the general character of the circulation. t would appear that when the pulmonary pressure is verv lugh. then the pul- J^^.Wu^-^'^y^^^ m iiAij|u|j^i| Figure 10. monary arterioles, etc.. are put on such a high tension that the regular respir- atory movements of the lungs are not sufficient to cause much change m the relative movement and volume of blood in the pulmonary vessels, as indi- cated in the tracing made by the pulmonary tambour. Adrenaline causes a general shifting of the blood volume and thus indirectly affects the pul- monary pressure. We wish now to take up another phase of the subject. It was long ago shown by Joseph" that acid solutions of arsphenamine could produce precip- Pa«e 218 D. E. JACKSON AND G. RAAP itation in the blood if the concentration of the drug exceeded 0.1 ])er cent. And Danysz'" has attempted to show that precipitation of the arsphenamine occurs both in vitro and vivo even with alkaline solutions. Smith, ^ in the light of these and other previous observations, has carefully studied this point with reference to the action of solutions of arsphenamine on serum in vitro. He finds that acid solutions (dihydrochloride) of arsphenamine produce very bulky precipitates in serum in vitro, and also cause a great rise in pulmonary pressure if injected intravenously. In vitro the precipi- tate between serum and the monosodium salt of arsphenamine varies from * X , ^d{J.QT^*^ ^^^^^-^ /-f(y,ooo m\\\\\\\\mm\\\im\\m\\\wmm v^^^v^v ^^^^1« ^■Co^^- iiiiiiiimiiimiil ^ Figure 11. a distinct turbidity to a moderately heavy precipitate. But Smilh found that no precipitate occurred in vitro between dog serum and alkaline arsphena- mine solutions containing 0.8 c.c. or more normal sodium hydrate per 100 mg. of drug. Smith has also shown further that perfusion of the lungs with a solution of arsphenamine dihydrochloride in physiological salt solution causes a contraction of the pulmonary vessels and a consequent decrease in the rate of outflow of the perfusion fluid. Since this occurs with acid arsphenamine solutions, it seems evident that the drug itself acts directly on the pulmonary arterioles to cause contraction, and that this is not entirely dependent on the alkali of the solutions as ordinarily used. Apparently then RANSOHOFF MEMORIAL VOLUME pulmonarv vascular obstruction may be due to an extensive precipitate of the drug to a'specific action of the drug itself on the muscle fibers of he arteriole .alls and to the presence of alkali in the solution used. In order to throw some further light on this question we have made injections of the drug into the femoral artery as shown in Fig. 9. In this case ,t will be seen that a dose of 12 c c produced a considerable rise in the pulmonary pressure. (The rise was really about twice as great as the curve shows, for a shght le-ik in the metal bowl of the tambour was allowing air to escape very slowly throughout the tracing. This was discovered after the experiment was over ) We believe that in this case the drug (injected into the peripheral end of the femoral artery) simply washed out the blood from the artery and then passed directly on into the femoral vein without being precipitated out to any marked extent in the leg capillaries. This then, was almost equivalent to slow injection into the femoral vein directly. . . ,r. We next proceeded to inject the salvarsan solution into a branch of the portal vein. In this case the solution had to pass through the liver capil- laries as shown diagrammatically in Fig. 4. Fig. 10 shows the result ot two uch injections (of 5 c.c. and 7 c.c). h will be noted that no rise occurred D. E. JACKSON AND G. RAAP in the pulmonary pressure, but on the contrary some sHght fall may have been produced. Fig. 11 shows first an injection of 5 c.c. of salarsan solution into the portal vein of a small dog. This ])roduced an obvious fall in both the pul- monary and the carotid pressures. Following this y> c.c. of adrenaline solu- tion was given. This caused a slight fall of pulmonary pressure, but only a faint rise of the systemic pressure. As a check on the action of the ap- paratus, etc., two other injections (3 c.c. and 10 c.c.) of salvarsan solution were finally given by way of the femoral vein. The latter of these produced a very obvious rise in the pulmonary pressure. These experiments evidently show that the liver has removed from the salvarsan solution its power to cause a rise in the pulmonary pressure. But on the contrary some por- tion of the drug must pass through the liver and on into the general circu- lation, for Fig. 11 shows that the salvarsan injections caused the systemic pressure to fall to zero and thus caused the death of the animal. This same point is further illustrated in Fig. 12. Here 40 c.c. of 1 ])er cent, salvarsan solution was injected (between the points marked x, x). This dose by femoral vein would certainly have raised the pulmonary pressure to a great height. Here, however, only a gentle rise in the pulmonary pressure was produced, and this appears as if it might have been due simply to the addi- tion of solution to the blood volume of the animal. But nevertheless, tliis dose of the drug still exercised a very obvious toxic action on the animal. Near the end of the tracing an attempt was made to inject salvarsan into the femoral vein. Three and one-half c.c. were injected which started to produce an immediate rise in the pulmonary pressure, but unfortunately some air passed into the vein through the injecting cannula and the animal died of air embolism (verified at autopsy). The marked rise in the ]nil- monary tambour here, however, serves as a valuable check on the technic of the experiment and shows that any rise which the salvarsan might have produced in the pulmonary pressure would have been promptly recorded. We feel obliged to conclude, therefore, that if salvarsan solutions be injected into the portal vein, the passage of the drug through the liver will almost, if not totally, remove its power to raise the pulmonary pressure. It is prob- able that this action occurs to some extent, and this may be rather marked in some instances, in the case of the arterioles and capillaries of the leg also. But the liver seems to be much more effective in this direction than are the tissues of the leg. It seems probable to us that this action of the liver results mainly, if not entirely, from a precipitation of the major portion of the salvarsan within the organ itself, perhaps in the form of emboli in the liver capillaries. The well-known detoxicating action which the liver manifests toward manv poisons is not probably extensively concerned in this matter, at least not in the manner in which such detoxication is usually considered. There is a rather striking significance in the rapidity with which this precipitation must Page 2r,l RAXSOHOFf MEMORIAL VOLUME occur in the liver, if this i> the correct explanation, for evidently only a very small proportion of the pulmonary pressure raising substance passes the liver, while at the same time very obvious effects from the drug may be IJroduced in the carotid pressure immediately. This point perhaps has a bearing on the marked symptoms of liver disturbance, jaundice, etc.. which are frequently manifested clinically in arsphenamine poisoning. CONCLUSION'S. 1. First-class preparations of salvarsan have almost no direct action on the bronchial musculature of the dog. It seems obvious that acute symp- toms resembling anaphylactic shock, or the so-called "nitritoid crises," if produced by good preparations of salvarsan cannot be due to a spasmodic contraction of the bronchioles. But we are not sure that this action might not occur in the case of esi^ecially toxic samples of the drug. 2. We have studied the action of salvarsan on the pulmonary pressure by means of an especially sensitive method. We believe that even the smallest injections of salva'-san exercise some immediate action on the pul- monary pressure. Its detection depends only on the sensitivity of the method employed for its investigation. ?i. When the ptilmonary pressure has l>een greatly raised by salvarsan we have noted that injections of adrenaline tended to lower this pressure, and also to restore the excursions of the pulmonary pressure due to the respiratory movements of the lungs, when these had been previously greatly reduced by the salvarsan. We believe this results mainly from a mechanical shifting of the blood from the action of the adrenaline on the systemic vasculature. 4. When solutions of salvarsan are injected into the general circulation by way of the femoral artery the ])ulmonary blood i)ressure is still raised by the drug. But the rise in pressure is less than if the drug were injected by the femoral vein. 5. When solutions of salvarsan are injected into the portal vein and are thus carried through the liver before ])assing into the general circulation, then it is found that the drug produces but little if any effect on pulmonary pressure, although if the dosage is very large the pulmonary pressure may be raised slightly, apparently only as the result of an increased volume of fluid in the vessels. But toxic doses thus injected tend to lower the pul- monary pressure. 6. We believe this action of the liver is brought about by a precipitation of the drug in the capillaries and arterioles of the liver. This apparently does not correspond to the ordinary detoxicating action of the liver as mani- fested on many poisons. 7. This precipitation in the liver takes place quickly and it does not pre- vent some portion of the drug from passing on into the general circulation. D. E. JACKSON AND G. RAAP For the systemic pressure may fall to a proportionately much j^^reater degree than does the pulmonary pressure. REFKRKNCUS. 1. Jackson. 1). !■:.. ami Sniitii, JI. I.: Jour. Pharmacol, and Kxper. Therap., 1918, xii. 221. 2. Jackson, 1). K. : Jour. Pharmacol, and Kxper. Therap., 1914, vi, 57. Experimental Phar- inacology, 1918, C. \'. iMosby Co., St. Louis, p. 287. 3. Smith, M. I.: Jour. Pharmacol, and E.xper.. Thfra])., 1920, .xv, 279. 4. Schamberg, J. F., Kolmer, J. A., and R.i,.,~ , . : W \,n ]..u, Med. Sc, 1920, clx. No. 2, p. 188. See also Kaiziss, G. W., and Proskf.m ' ' i , i ,,t .\rsphenamine and Its Relation to Toxicity, Arch. Dermat. and Syph., ]'.■ r i l..,hiur, J., and Lucke, 1!.: Pathologic Changes after Arjphenamine and Nm , ; s'l Koth. C. B. : Tox- icity of Arsephenamine and Neo-arspbenamine, ibi'i , i' J'' st.k-., I H : Therapeutics of Ar- sephenamine, ibid., p. .^M. Stetson, D. D. : Permanent Solution of Arsphenamine. ibid., p 324 Hanzlik, P. J., and Karsner, H, T. : Jour. Pharmac. and Exper. Therap., 1919, xiv, p. 425; ibid., 1919, xiv, p. 375. 5. Stokes, J. H., and Busman, C. J.: Jour. Am. Med. Assn., 1920, Ixxiv, No. 15, p. 1013. 6. Jour. Lab. and Clin. Med., 1920, v, 745. 7. Milian: Les intolerants du 606; Bull. Soc. franc, de dermat. et syph, 1913, xxiii 5 '0 L'administration de I'adrenaline. Paris Med., 1918, 2 fevrier. 8. Becson, B. B.: Am. Jour. Syph., 1919, iii, p. 129. 9. Joseph, I). R.: Jour. Exper. Med., 1911, xiv, 83; ibid., p. 179. 10. Danysz: Ann. de ITnst, Pasteur, Paris, 1917, No. 3, p. 114. A CASE OF CANCER OF THE \AGINA. CERMX AND BODY OF THE UTERIS TREATED V,\ RADIUM. HowAui. A. Kixi.v Even in these days of easy and constant connnunication. when our tens of thousands of Aescula]iians have one and all become devotees of the peri- patetic philosopher, surgery still advances as heretofore through the ideas developed in sundry pregnant centers where dwells the great man. From the time of Joseph Ransohoff's activities from the earl\ eighties on. Cincin- nati has been recognized as one of these fruitful centers, a source of emana- tions of great ideas in the surgical field. His work is especially characterized by its catholicity, embracing as it has gynecology — see his paper on "Two ovariotomies in the same patient" (1885) — his work on the anatomy oi the cecum and appendix (1888). when appendicitis was just beginning to attract attention; his brain surgery, his hernia work, his gall-stone o[ierations. and ;rapli sliovving tissue rciiK.v.il l,y ciiicttemetit of ult-nis licfore ratlimii tri'atinciit. .\. indicates invasion of epithelioma into uterine wall. above all. what attracted my own attention the most, liis splendid contribu- tions to the surgery of the kidney, when that important organ was still a terra incognita for the average surgeon. Aside froiu his distinguished and widely recognized (|ualities as a surgeon. Dr. Ransohofif was one of the ])ioneers of this country in the recog- nition of the value of radium as a therapeutic agent, either co-operative with surgery or substituting it or yet again operative in cases where surgery is impotent. .A large e.xperience thus enabled him soon to lay down the rules of dosage and a])])lication so difficult in this new field, where so much danger lurks in overdosage. I refer particularly to such publications as : Page .'.J( HOWARD A. KELLY Radium Treatnient (jf Cancer (with J. L. Ransohofif), Lancet-Clinic, 111, 661 (1914). Radium Treatment with L'terine Cancers (with J. L. Ransohoff), Ann. of Surg.. 64, 298 (VnG) ; Trans. Am. Surg. Assn.. ,54. 202 (1916). Radium Treatment of L'terine Fibroids, Lancet-Clinic, 115, 116 (1916). The following case illustrative of an extensive cancer of the cervix, uterus and vagina, with the sketches and sections made in the cour.se of the treatnient and progress towards recovery, is reported as one of the inter- esting and remarkable examples of the potency of this newest and most \o. 2. Photomicrograph showing^ tissue removed liy ciirettemenl ten weeks after radium treatment. The hyaline tissue is typical and follows lieavy radiation. Note complete absence of epithelium and the thick wall of the blood vessel in the upper left hand portion in the midst of the hyaline tissue glands. wonderful of all our remedies, in the field which Dr. Ransohoff has culti- vated with such assiduity and success. The patient, J. H. M., No. 5902, a woman 56 years old, consulted me January 2(1, 1920, complaining of bloody vaginal discharge, pain in the back, pelvis and linilis. loss of weight and bladder irritability. Her family history was negative. Past history : Health always good : no serious illnesses; no operations; menstrual history normal; menopause at 48 with no symp- toms. Marital history: Five children, all spontaneous deliveries. Present illness ; In the spring of 1917 patient noticed a slight intermittent leucor- rhea which gave her no particular trouble until April, 1919, when it became constant and at times blood-tinged. This became more profuse, and from .August, 1919, on, it was bloody. In November, 1919, she began having pain in her back, radiating into the pelvis and limbs, .^bout the same time she noticed bladder irritability with constant desire to void. For the past three or four months there has been progressive weakness. General physical examination negative except for some pallor and evidence of recent loss of weight. No enlarged lymphatic glands anywhere. Pelvic examination : Vagina short ; pronounced rectocele ; cervix at first touch appears normal, but on closer examination it is softish and nodular, the anterior lip more involved than the posterior — the anterior lip is fused with the anterior vaginal wall and there is a submucous thickening extending from the junction of the cervix and anterior wall to the orihce of the urethra. The uterine body is somewhat enlarged; there is no evidence of lateral disease, or thickening in either broad ligament. On with- Pagc .:.;s RAX so H OFF MEMORIAL VOLUME drawing the gloved hand there is quite a little bloody discharge. -Inspection in the knee-chest posture shows a submucous thickening extending over the anterior lip of the cervix down on to the vaginal wall. There are several little granular areas which bleed easily on touch. Protruding from the cervical canal there is a fringe of friable tissue. Examination under anesthesia confirmed without adding to the above findings. Dila- tation and curettage showed a cervix enlarged, easily dilated, filled with friable tissue which, when curetted, leaves a crater. The body of the uterus was packed with the same friable tissue. Tissue from both cervix and body of uterus showed a basal cell epithelioma. Treatment : On account of the extensive local uterine involvement and the definite extension over the entire anterior vaginal wall, radium was advised in preference to operation. On January 30, 1920, she was given 1208 millicuries screened with 2 mms. of brass and 1 mm. of rubber for three hours and forty minutes— three-fourths of the treat- ment distributed on three areas in uterine cavitv and one-fourth in cervical canal. Xo. 3. Photomicrograph showing tissue removed by curettemeiit nine months after radium treatment. This shows the end result following radiation. Note the fibrous tissue and the distended glands. Patient was a little nauseated from the treatment, but no mure upset than she was following the dilatation and curettage. She returned home on February 2. She came back on .April 15. 1920. .-Ml of the bloody discharge had stopped the second week in February. Since then there has been a scanty, serous discharge. She has had no pain, and has gained several pounds in weight, and appears to be in splendid health and is stronger — in fact, she has none of her former symptoms. \ pelvic examination showed the cervix contracted, perfectly normal, absolutely freely movable in every direction — uterine body upright, a little enlarged but perfectly freely movable. There was a slight bloody discharge after examination. Inspection showed the cervix normal. The anterior vaginal wall was also normal, and palpation shows no extension on the anterior vaginal wall. Curettage of the uterine cavity obtained a little necrotic tissue, the curet quickly reaching a firm, fibrous, grating base. Microscopic examination of tissue showed hyalinized fibrous tissue with no epithelial cells. On September 24, 1920, patient had gained in weight, strength and in every way. Has had a troublesome leucorrhea for the past two months, but no bleeding. Has been having some neuritis in limbs and is neurotic and apprehensive. Pelvic examination shows vagina negative as to any evidence of disease. Cervix normal, senile, atrophic. Uterus upright, not definitely enlarged. In contact with the vagina there is a sensation of resistance posterior on the right. Per rectum this thick- ening is definitely felt with the finger, but it is more like that which is due to simple lack of flexibility of the tissues rather than disease. There is no evidence of meta- stasis in iliac or inguinal glands. On dilatation there is a discharge of pus and on Page SSe HOWARD A. KELLY curettement a necrotic material (pyomctra) is obtained — curctteinent quickly readied a firm, muscular base. Curettings examined microscopically showed only radiated tissue. After this examination was completed and the patient was reassured that there was absolutely no evidence of the old trouble, she was much relieved and during the rest of her stay sutTered little from the neuritis which she complained of at home. Note. — All these slides were made immediately a sections stained with hematoxylin and eosin. It is of satisfactory slide records can be made in this way, t delay. This method of immediate examination eman; worked out by Dr. Thos. S. Cullen. It has now been It is, however, not generally known that it obviates, ir the time of the examination, and are frozen reat importance to know that permanent and us saving much laboratory labor as well as :ed from my laboratory, where it was first 'idely adopted in Europe as well as at home, many cases, further section cutting, as here. Page ?.57 THE DIAGNOSIS AND TREATMENT OF DIAPHRACxMATIC PLEURISY: WITH REPORT OF CASES.* By T. H. Kellv. B. S.. M. D.. ami H. B. Weiss. A. B.. M. D. Cincinnati. For many years it has been noted that not infrequently a pneiinionia begins with symptoms resembhng acute abdominal disease, particularly in children. J. P. Crozer Griffith' reported several cases, as did also Herrick- and others. Needless to say. many clinicians have suffered the experience of advising operation for some acute intra-abdominal condition, only to find the abdominal contents normal and a pneumonia in one of the patient's lower lobes the day following the operation. To Capps^ we owe the well-defined picture of invohenient of the dia- phragm by inflammatory processes. He published in 191 1 the results of experimental irritation of the diaphragmatic pleura in a series of human beings, the work being done upon patients with pleural effusions. Irritation of the diaphragm was accomplished by means of a wire introduced through a trocar inserted into the pleural cavity preparatory to the withdrawal of the pleural effusion. His observations covered experiments upon seventy-five patients, only thirty-five of whom presented favorable conditions for free exploration of the diaphragm. He also presented in the paper a very com- plete discussion of the previous work, which has been published upon the innervation of the visceral and parietal pleura. He concluded from his experiments that : 1. The visceral pleura is not endowed with pain ^ense. 2. The parietal pleura is richly supplied with sensory fibers from the intercostal nerves and irritation of it produces pain that is accurately local- ized by the individual over the spot that is touched. Such irritation never gives rise to "referred" pain in the neck or elsewhere. 3. The diaphragmatic pleura receives its nerve supply from the last six intercostal nerves, which supply a peripheral rim of the diaphragm two or three inches wide anteriorly and laterally and a segment corresponding to the posterior third, and from the phrenic nerve which supplies the central portion of the diaphragmatic pleura. The pain produced by irritation of the central part of the diaphragmatic pleura is a true referred pain, and is distributed over the skin and tissues supplied by the third and fourth cervical segments, with a predilection for the trapezius ridge. The pain elicited by irritation of the peripheral or posterior jiortion of the diaphragmatic pleura is also a true "referred" pain. The pain is usually •From The .American Journal of the Medical Sciences, December, 1918. From the Department of Internal Medicine. University of Cincinnati, the Medical Clinic of the Cincinnati General Hospital and the Wi'helra and Gette Beckman Dispensary. Page 258 T. H. KELLY AND H. B. WEISS distributed in segmenta areas over the lower thorax and epigastrium, some- times extending downward over the whole abdomen on the same side (sev- enth to twelfth dorsal segments). Both pains are spontaneous and are associated with hyperesthesia and hyperalgesia of the skin and superficial tissues on pressure. 4. The pericardial pleura receives its innervation chiefly, if not exclu- sively, from the phrenic nerve. Irritation of this part of the pleura results in "referred" pain in the neck of the same character as that following irri- tation of the central portion of the diaphragmatic pleura. This work offered a definite starting-point from which to work in the diagnosis of involvements of the diaphragmatic pleurae, and in 1916 Capp^' published a series of sixty-one cases of diaphragmatic pleurisy, in all of which the diagnosis was confirmed either by autopsy or the subsequent his- tory of the cases. In this article he called attention to the various distribu- tions of the referred abdominal pain, and emphasized the points of ditifer- cnce between it and the pain of true abdominal disease. The skill and muscles of the abdomen are more sensitive in referred pain from the diaphragmatic pleura than in abdominal visceral disease, and the cutaneous reflexes are more lively in referred pain. Deep pressure with the flat hand is better born in referred diaphragmatic pain, while it produces deep pain over an inflamed organ within the abdomen. The presence of sharp localized pain in the neck, occuring spontaneously or only on pressure, on the same side as the abdominal pain often suggests the true state of aiifairs, as it indicates irritation of the phrenic nerve. The referred pains in the neck and abdomen are often aggravated by cough or deep breathing. Also, in acute diaphragmatic disease there are usually present evidences of respiratory infection, such as cough, expectoration, herpes labialis, rapid respiration, high leukocytosis, etc. According to Capps, hiccough is not common in diaphragmatic disease, as was formerly supposed, having oc- curred only five times in his sixty-one cases. The differential diagnosis of involvement of the diaphragmatic pleura and abdominal disease is very important, and at times the clinician is in a veritable whirlpool of indecision concerning the correct diagnosis. We have had the opportunity in the past two years of observing in the Cincinnati Gen- eral Hospital and the Wilhelm and Gette Beckman Dispensary a number of patients exhibiting some or all of the features mentioned by Capps in his dscription of diaphragmatic pleurisy. In certain of these cases the question of surgical intervention was quite acute and the importance of correct diag- nosis therefore correspondingly great. From these cases we have selected twenty-two in which the diagnosis was confirmed either by their future course or at the autopsy table, and are presenting them, hoping to show the variations in the manifestations of diaphragmatic pleural disease and the different paths by which we arrived Page ..'.;;» RANSOM OFF MEMORIAL VOLUME aa see O V V U V ^ -s ; C; U-, o O c: ■si|3j pooiq ajiqM S5^oo_io_'^^oo5 ^S IcviS?^ ;o6:^j\oo6c :o8S88nooo8! X : : : :xx : : : :xx : :x :x : : :xx : :xxx x : : : :xx : :xo XXX ^ .SS ■,.SS ?^ XXX :x : :xxx x :xxxx :xxx^ xxxxx : :xxx x :xxxxxxxx2 xxxx»xx :x : xxxxxxxxxx: ::;::::: :x :xxxxx : ; : :' Sb;ssfi;sstes: ;sss2fefe'SSfe j^invoi^oOC^O — ^^ r. H. KELLY AND H. B. VVFJSS at a diagnosis in the different instances. The table on page 4 shows the symptoms, both subjectixe and (ilijective, that were found in onr cases. (See Fig.s. 1, 2, .1) Fig. 1, Ca.se 1. Showing points of tendcrnL-ss along the trapezius and beneath the twelfth rib posteriorly. Of these twenty-two cases, ten were acute in cliaracter, three had acute exacerbation at the time of observation and nine were subacute or chronic. The following cases in the first group resembled surgical conditions so closely that the question of operati\e intervention was seriously considered : l'"ig. 2, Case 2. Showing points of tenderness along the trapezius, in solid marking, and the stippling showing areas of hyperesthesia and hyperalgesia. No. 1, renal stone; No. 4, acute cholecystitis; No. 6, cholelithiasis with colic; No. 8. generalized acute peritonitis from perforated typhoid ulcer; No. 14, operation was done for an acute appendicitis, much to our chagrin ; Nos. 18 and 22 both had operation for gall-bladder disease several years RANSOHOFF MEMORIAL VOLUME previous to the time of obserxation. In both cases neither stones nor any other pathological condition were found at operation, and shortly afterward there was a recurrence of the symptoms that had existed before the opera- Fig 3, Case 3. Showing points of tenderness along the trapezius posteriorly and tenderness heneath the twelfth rih and an area of hyperesthesia over the fourth dorsal spinous process. Fig. 4, Case 12. .\ lateral view showing areas of hyperesthesia and points of tenderness along the trapezius and beneath the twelfth rib posteriorly. tion. In the remaining cases of the acute group the symptoms or history immediately gave an inkling as to where the seat of the trouble lay. In the group of chronic types the question of surgical treatment arose in No. 7, which is interesting because it combined definite symptoms of dia- phragmatic pleurisy and a chronic appendicitis, which were both proved by the further history of the case. In the acute cases the symptoms arose sudi T. H. KELLY AND H. R. WEISS denly, as with the onset of pneumonia, and after several weeks practically all the symptoms had left. On the other hand, in the chronic cases, the onset was acute and the symptoms subsided, but at irregular intervals there was a recurrence of the symptoms, in whole or in part, usually without an increase in temperature and not with the original acuteness. At these periods of recurrence exertion and cough intensified the symptoms, and frequently exertion was the cause of the recurring attack. The chronic sutYerers com- Fig. 6, Cast- 1. Sliuwing a definite area of infiltration six days after the first picture was taken. Paul' 'M3 RAXSOHOPF MEMORIAL VOLUME jilained just as biitcrly of the pain and, occasionally, of the hyperesthesia as those who suilered from an acute attack. Hyperalgesia and hyperesthesia were not always marked, being present in seven cases. The hyperesthesia, when present, was most acute, and one Fig. 7, Case 6. Showing the position of the diaphragm and markings of the right lower base. One month alter this plate was taken another pair of stereoscopic plates "failed to show the shadows at the right base which were seen on the previous plates." Fig. 8, Case 1.3. Showing di diaphragm liv adhcsii of the patients cried out when the tips of the fingers were passed over the skin. In one patient clothing was almost unbearable. The involvement in hyperesthesia was usually over a large area. (See charts.) Hyperthesia Page nei T. H. KELLY AND H. B. IVFJSS and hyperalgesia were nuicli more apiJarent in the acute than in tlie clironic cases as a rule. In the great majority of cases deep abdominal pressure was borne quite well. Spontaneous pain was not always present in the neck- when pain on pressure was marked. The two most constant areas of tenderness on ])ressure were below the twelfth rib posteriorly on the afTected side and at the ridge of the trapezius, though the patients did not always complain of spontaneous pain at these points. The upper quadrants of the abdomen were the most frequent sites of the referred abdominal pain. In many of the cases the abdominal pain radiated toward the flanks, and in two of them there was definite tenderness, involving the. entire half of the back from the lower ribs to the ilium. There was usually moderate rigidity and muscle spasm of the abdominal mus- cles at the areas of referred pain. Abdominal symptoms of varying degree were present in nineteen of the twenty-two cases. In two cases there wa> board-like rigidity over the abdomen. One was oj)erated for relief of acute appendicitis and the appendix was found apparently imiocent of any dis- ease. In the other case (No. 8) the rigidity and muscle spasm continued until there appeared definite signs of consolidation in the left base. This is the only patient who died, and at autopsy the pathologist reported: "In the left pleural cavity there were a few acute fibrinous adhesions over the left lower lobe and no fluid. The pleural surface of the left side of the diaphragm was congested and had about its middle point and extending pos- teriorly from this a small amount of fibrin, some of which was undergoing organization. Beneath this and surrounding it there was exceedingly well- marked venous congestion. The peritoneal surface of the diaphragm showed nothing but slight congestion. The lower lobe of the left lung showed a diffuse lobar consolidation, and all of the bronchi of this lobe were filled with pus. There were no abnormal findings in the abdomen." Capps states that in his series of sixty-five cases hiccough appeared in only five cases, while in our twenty-two cases this symptom occurrt>d in two cases, and in both was quite intractable, all of the usual methods for its relief failing, the hiccoughs apparently ceasing spontaneously. Fourteen of our cases were males and eight were females. C.astric symptoms were not frequent. One case showed both nausea and \-omiting, while nausea and vomiting were present, each once, in separate cases. In seven cases friction sounds were heard, prjictically all in the lower axillary region of the affected side. These friction sounds were probably due to an associated involvement of the costal pleura. Five patients had pneumonia associated with their pleurisy. In the majority of the acute cases there was a rise in temperature, though not very high. The leukocyte count was in- creased, depending on the acuity of the symptoms as a rule ; associated with the increase in leukocytes there was a proportionate rise in the polymor- phonuclear neutrophile cell count. RANSOHOFF MFMORIAL VOLUME In but four of the nineteen cases examined by the Roentgen rays there were no findings suggestive of pleural or pulmonary involvement. The Roentgen-ray finding varied, ranging from definite distortion of the dia- phragmatic contours to merely a definite increase of the hilum markings radiating to the border of the diaphragm. In several instances, shadows suggesting calcification were lying close to the diaphragm. In two of the accompanying reproductions of Roentgen-ray plates one can see in the early picture a finger-like infiltration above the diaphragm and in the latter picture the shadow of a definite infiltration of the lung in the same region. The diagnosis of diaphragmatic pleurisy was usually made on the occur- rence of pain in the side, associated with pain beneath the twelfth rib on the affected side and along the edge of the trapezius on that side. The jiain may be spontaneous in the neck and was so in one-third of our cases. In nine- teen out of twenty-two cases there was tenderness along the edge of the trapezius. There is almost a constant finding of tenderness on pressure beneath the twelfth rib posteriorly on the affected side ; this symptom was present nineteen times in twenty-two cases. In the vast majority of the cases there is referred pain in the abdomen, with varying degrees of muscle spasm and rigidity. A moderate rise in temperature with an increase in the leukocytes and polymorphonuclear cells is usually jiresent. In some cases there are heart friction sounds in the lower axilla. The Roentgen-ray examination of the chest in over three-fourths of the cases did shorv definite diaphragmatic involvement or pulmonary involve- ment close to the diaphragm. In chronic cases there is exacerbation of the characteristic symptoms on exertion, cough and frequently on deep inspiration. Treatment. In the acute cases the treatment is that of any pleuritis. We have found that cold applications, in the form of iced-linen strips, applied (and frequently changed) to the aiifected side for two hours, is most effica- cious. Of course, sedatives are used when necessary. Strapping the lower chest and upper abdomen seems to give the greatest relief, and man\ of our chronic cases return to us asking that their sides be strapped. They have found that after the side has been strapped their pains will be relies ed almost immediately and that they will be free from their annoying sym])toms for from several weeks to months. We are indebted to Mr. R. Isaacs for the accompanying charts. BIBLIOr.R.AiPHV Griffith: Toiu . .Am. Med. Assn.. 190.1. xi. .S.ll. Herrick: Jou r. Am. Med. Assn., 1903, xi, 535. Capps: .Arch. Int. Med., 1911. No. 6. viii, /l/. Capps: .Am. lotir. Med. Sc. 1916. No, 3. cM. 33.1 DEMONSTRATION OF THE INTERVENTRICULAR MUSCLE BANDS OF THE ADULT HUMAN HEART.* By H. McE. Knovver Cincinnati. This demonstration is made on a specimen of adult human heart in which the fat, coronary vessels and epicardium have been removed to expose the superficial muscle fibers of the ventricles and of the conus. This super- ficial sheet is cut on the posterior surface to the left of the posterior inter- ventricular groove (sulcus longitudinalis posterior), and the right ventricle rolled away from the left after the method followed by J. B. Macallum with pig embryos' hearts. The septum is thus split open, exposing the inner terminations of the muscle bands which arise superficially from the right and left atrio-ventricular rings, and from the conus, and end in the papillary muscles of the left ventricle. Deeper fibers are also shown, extending from the left ring to the large papillary mu.scle of the right ventricle, and from the conus to this papillary muscle. The membranaceous septum is split, showing the position of the atrio-ventricular bundle of His in a novel and striking manner. The septal blood-vessels are also found readily. The right and left ventricles may be thus unrolled furthej until opened from the septal side, as done by Macallum for young pig hearts. A fair proportion of hearts taken from dissecting-room subjects, preserved by injection of car- bolic, glycerin, alcohol solution and afterward kept for a time in cold storage or in vats of weak carbolic, are found to be suitably macerated for this demonstration. The results of Winkler, Pettigrew, Ludwig, Krehl and Macallum are thus readily examined in the human heart ; we believe for the first time. It is urged that students should be induced to .study the heart in this way, after working out the coronary circulation, etc., rather than to simply cut open the ventricles after the method used by the pathologist in autopsy, since these cuts destroy the important muscle connections. The tracing of the muscle bands between the right and left ventricles will furnish a valuable aid to the better appreciation of the action of the heart. The relations of the papillary muscles to the interventricular (and conus) muscle bands can hardly be understood without this dissection. The study has since been confirmed and e.xtended by F. P. Mall, 1911. in his Muscular Archi- tecture of the Ventricles of the Human Heart, .Vmerican Journal of Analomy, Vol. H. p. 2IJ, etc.; also, by J. Tandler, 1913, in his Anatomic des Herzens, Vienna, p. 171. the proceedings of the .Amer OCL'LAR AXGIO-SCLEROSIS.* r.y GicoKci.; H. Kkkss. R. S.. M. D. Los Angeles. THE TERM AXGIO-SCLEROSIS. Ocular angio-sclerosis. as a term to indicate the hardening or over- growth of connective tissue of the walls of the blood-vessels of the eye, is perhaps a better term under which to group the type of changes to be here discussed, than to refer to the process either as arterio- or phlebo-sclerosis, although it must be confessed that the term arterio-sclerosis. through com- mon usage, conjures up the most definite conception to the minds of many of us. The study of sclerosis of the vascular system is especially interesting to ophthalmologists, because in the eye, as nowhere else in the body, do we find an organ with terminal arteries where many of the changes in the structure of the blood-vessels can be thoroughly examined from day to day. VASCULAR SCLEROSIS CLOSELY ASSOCL\TED WITH FAULTS OF OUR CIVILIZATIOX. The close association of sclerosis of the vascular system with some of the major faults and vices of our civilization, such as over-eating, high ten- sion living (both mental and physical), alcoholism, and syphilis; and its intimate connection with chronic nephritis (perhaps as often a percursor as a corollary of the last-named disease) ; as well as with the fault of simple old age (a condition most of us aspire to in spite of its defects and disad- vantages), even though we are less disposed to accept that of our heredity, a causative factor also to be reckoned with ; and the further fact that vascular sclerosis more often manifests itself after the age of forty, at which time most persons have occasion to seek the services of an oculist ; and that a careful examination of the fundus at that period may give important data at just the time when there may be few other clinical symptoms of arterio- sclerosis elsewhere, should make this subject one of equal and nf \ery con siderable interest to eye specialists and to general practitioners alike. AXGIO-SCLEROSIS A GRAXE DISEASE. General arterio-sclerosis is a condition not to be permitted to go on to terminal or very frank stages, if health and life are to be conserved ; and ocular angio-sclerosis, not alone because of its capacity to impair vision, but because the changes of the sclerotic process are in the eye sometimes earlier or more evident than in other portions of the body, can therefore, be the means of earlier diagnosis and proper treatment; and through its early recognition we may be in a position to prolong the life of a considerable number of our patients. •From The Ophthalmoscope, December, Page 268 GEORGE H. KRESS OCULAR ANGIO-SCLEROSIS FREQUENT PAST THE AGE OF FORTY. Hirschberg. in a series of cases of old persons coming to him for refrac- tion, found evidence of retinal angio-sclerosis in 50 per cent., and micro- scopic examinations of the retinal vessels of old people show, according fo Hertel, an even higher percentage of sclerotic invohenient than this. HYPERTEXSiOX A FREOUENT CONCOMIT.KNT OF ANGIO-SCLEROSTS : AND THE NEED OF DETERMINING WHETHER HYPERTENSION EXISTS. Since the sclerotic changes are so often a.^^^ociated with hypertension of the vascular system, the question suggests itself as to whether it should not be a routine practice for eye specialists to take the blood pressure of all patients seeking refraction about the age of forty and after ; to the end that a special effort may be made to obtain an exact record of the condition of the ocular vascular system in such persons as give evidence of increased blood i)ressure. The fact that an increased general blood pressure so dis- covered may also enable us the better to guard against glaucoma, is likewise important to eye specialists. Increased vascular blood pressure has also been noted in connection with cataract, and even though it is not possible to stop this lens change, appro- priate treatment may, before cataract extraction, somewhat reduce the dan ger of post-operative hemorrhage. The fact that it is still a matter of discussion as to whether vascular hypertension is or is not antecedent to vascular sclerotic changes, need not concern us, since we are in possession of the important fact that nearly always this hypertension is one of the early manifestations or concomitants of vascular sclerosis ; although it must be remembered that there be those who believe that in this early stage, a hypotension may alternate with a hypertension (the latter construed to be dependent at this stage upon a spasm of the muscular coats of the arteries). IXTRA-OCULAR GLOBE TENSION MIGHT ALSO WELL BE TAKEN. In taking these blood pressure readings, it might well be a part of our routine to take also a reading of the intra-ocular globe tension with a Schiotz tonometer or a Gradle or other modification. The tonometer (using 1 per cent, holocain, which is slightly antiseptic, and which does not exfoliate the corneal epithelium, as does cocaine, to anesthetize the cornea) can be quickly used; and the information received from such a tonometer reading is gen- erally conceded to be far more accurate and valuable th;in that from linger palpation. THE NOR.^L\L AN.\TO.\lV OF THE RETINAL BLOOD-VESSELS. According to Oalman. in the large central artery of the optic nerve, there can be deiuonstrated an outer (adventitial of coimective tissue; a middle (or media) of elastic and fibrous tis-,ue. interspersed with a few RAXSOHOFF MEMORIAL VOLUME muscle elements: and an innter (or intima) made up of ( 1 ) an elastic lamina; (2) a subendothelial layer, and (3) a stratum of endotlielial cells. As the central artery appears on the disc, however, and its branches get farther away therefrom, the above-mentioned subendothelial layer and elas- tic layer of the intima usually give place to a few elastic fibres only. .\s regards the normal veins, however, in the retinal divisions uf the nor- mal central vein, this subendothelial layer, and the so-called elastic membrane of the intima. are lacking; and the retinal veins are. in fact, little more than tubes of fibrous tissue lined by endothelial cells. THE MORBID AX.ATOMV OF THE RETINAL BLOOD-VESSELS. It is not necessary for our purpose to go into much discussion concerning the microscopic morbid anatomy of the sclerosed blood-vessels other than to reiterate that in the arteries, the inner coat shows a thickening, either from patchlike areas of endothelial proliferation, or from a very consid- erable addition to the subnedothelial connective tissue (the latter more of a fibrosis, and then process most often met with in the veins) ; the middle coat presenting usually areas of necrosis and hyaline and fatty degeneration, with formation of atheromatous detritus, which may or may not be later on infil- trated with calcareous material. The outer coat in more advanced cases may also show thickening, but whether this is due to the circulating to.xins or is only an evidence of compensatory thickening or protection of the ves- sel wall, is not yet determined. In phlebo-sclerosis. the intima likewise shows the increase of connective tissue in the internal coat, and the degenerative changes in the outer layers, with a weakening and widening thereof, or if calcareous dejiosits be asso- ciated, then a stiffening or hardening of the vessel. These facts concerning the normal and abnormal anatomy of the retinal blood-vessels should be borne in mind in any consideration of the changes which take place in ocular angio-sclerosis. HOW THE IXTERXAL EYE TUNICS SUEEER THRt)LC.H ANGIO-SCLEROSIS. .A.S a result of the angio-sclerotic changes, the eye tunics are supplied by blood-vessels with narrowed lumina and bathed with blood containing the toxic elements lying at the root of the sclerosis. Consequently, the nutrition and metabolism of the retinal and other ocular tissues sutYers. Associated with the above factors are the weakened vessel walls and their greater tend- ency to leak and be responsible for hemorrhagic spots in the retina. THE EFFECTS OE ANGIO-SCLEROSIS ON VISION. Sudden diminution of vision of marked amount does not. however, usually result from angio-.sclerosis, except when the sclerotic changes occlude the lumen of the central artery or vein ; or, with more extensive weakening of the ocular vessels, are responsible for a sudden intra-ocular hemorrhage. GEORGE H. KRESS A weakness in the visual power in persons ])ast fort)-, whicli does not respond to suitable refractive correction, should, howexer, lead to a suspi- cion of vascular changes, and indicate a close examination of the retinal vessels to see if such changes can be discovered. SYSTEMIC SIGXS OF ANGIO SCLEROSIS ALSO WORTHY OF NOTE. In these patients in whom arterio-sclerosis is suspected, it is well also to have the blood pressure taken, and the heart examined to determine whether a hypertrophied left ventricle is associated with accentuation of the aortic second sound, or increased intensity of the first sound, or whether there is any displacement of the apex beat. A careful and periodical examination of the urine should also be made. If the picture of retinal angio-sclerosis be at all advanced, even though the general signs of arterio-sclerosis, be not prominent, the possibility of concurrent cerebral arterio-sclerosis, with its danger of apoplexy, should he kept in mind. CLINICAL STAGES OF SYSTEMIC AXGIO-SCLEROSIS. Just as in tuberculosis we deal with three stages of incipient, interme- diate, and terminal involvement, so also in vascular sclerosis do we find a beginning stage, difiticult of recognition; an intermediate stage, with franker signs ; and a terminal stage, in which the involvement is so general as to nullify much of our attempted therapy. It is in this third or last stage also that patients are seen in whom a steadfast hypo- may succeed a previously persistent hypertension. PECULIARITIES OF THE EYE STRUCTURE I.\ RELATION TO OCULAR ANGIO-SCLEROSIS. Without further comment, we can now pass on to a consideration of ocular angio-sclerosis proper, simply again calling attention to the fact that in the eye, we are dealing with terminal or end arteries of very delicate struc- ture, with little or no arrangement for compensatory circulation (although with the retinal veins there is more provision for a collateral circulation), so that endovascular irritants have full opportunity to make their power felt ; and, further, that because of the structure of the eye, we can use our dark room instruments in making close and .systematic observation of these changes, the handicap being not always that the changes are not present, but that in our haste we fail to note them. SUBJECTIVE MANIFESTATIONS OF OCULAR ANGIO-SCLEROSIS. Among subjective phenomena may be noted early decrease in the powej of accommodation, or severe headache persisting after refraction has been corrected at the onset of presbyopia. The subject of diminution of vision has alreadv been discussed. RAXSOHOFF MEMORIAL VOLUME OBJECrn-E SIGXS OF OCULAR ARTERIO-SCLEROSIS. Among the objective niaiiifestntidiis arc the fnllowing : neneral : Arcus senilis : Slow reaction of the pupil : Hyperfemic optic disc of dull-red color : CEdema of the retina (patches more often in the vicinity of the disc or blood-vessels). Course of arteries: a tendency to cork->cre\v course in one or more arteries, especially the smaller arteries and veins near the disc. Number of arteries : a seeming increase in the number of smaller retinal vessels, due to dilatation making them visible to the eye. Pressure effects of arteries: a disposition on the |>art of the harder arteries to flatten out the veins somewhat, at the places where the arteries cross the veins ; or it may be that the course of the vein at such a crossing, where it can ordinarily be traced beneath the artery without loss of con- tinuity, is lost until it reappears on the other side of the artery. Light streaks on arteries : an increase in the brightness of the light streak (the so-called "silver wire" appearance). Other streaks on arteries: with perhaps an associated continuous, or interrupted and somewhat nodular whitish streak of lesser brightness outside the vessel walls (this appearance being in the retinal peripheral vessels in contrast to the occasionally seen congenital connective tissue sheath of vessels which is limited largely to the disc area), these perivascular streaks being due to an infiltration in the lymph sheaths of the vessels, or to the fact that the usually transparent vessel walls in their now thickened state reflect more light from the blood stream than formerly. Color and translucenc\ ot arteries: a decrease in the color and tran-- lucency of the vessel walls. Locomotion pulse: with these changes may be present the so-called "locomotion," or arterial pulse, not dependent upon pressure, as in gloucoma. Such a pulse is often best seen where the arteries bend sharply. Venous pulsation : in advanced retinal arterio-sclerosis, because of the hardened blood-vessels, digital pressure on the eyeball may fail to bring out venous pulsation or blanching of the vessels. Calibre of arteries: while the arteries are not often widened in the earlier stages of retinal arterio-sclerosis, later on they may become narrowed. The larger arteries. f)r \eins. of the optic disc at times show some of these changes best. Disc margin ajjpearance ; in addition to the above, the optic disc and the larger retinal vessels may be surrounded by a greyish haze. Hemorrhagic spots : where the disease has made greater progress, blood extravasation may occur near the vessels, ranging from dots and short streaks to real blotches of hemorrhage. Page 272 GEORGE H. KRESS OCULAR ANGIO-SCLEROSIS A DISEASE AFFECTING BOTH ARTERIES AND VEINS; AND FURTHER SIGNS IN RELATION TO SOME OF THE PHLEBO-SCLEROTIC CHANGES. The changes noted above may not only involve veins as well as arteries, but also, to a certain extent, may be almost limited to the veins. This seem- ingly larger involvement of the veins in ocular than in general vascular sclerosis, may be explained in part perhaps because in the eye we can watch minute changes in the vein, size, course, etc., which because of less firm anatomical structures than the arteries, are less discernable through coarse finger palpation, etc., in other portions of the body. In the veins, also, there may be the picture of constriction and dilatation in dififerent portions of the same vein. If a hardened artery press firmly on a vein beneath, there may be dila- tation in the portion of the vein in the periphery of the fundus; while the part next to the disc is narrowed. The pressure of the artery helps the tendency toward the phlebitis, wiiich is already present as a result of the basic causes of the angio-sclerosis. If the vein walls weaken only in spots, then in lesser degree, the veins may show the bulbous varicosities seen in other parts of the body. With more advanced phlebities, and the secondary constriction of the vein lumen, spots of adjacent hemorrhage appear often also. BOTH INTRA- AND EXTRA-OCULAR HEMORRHAGES OF SIGXH-TCAXCE AS REGARDS ANGIO-SCLEROSIS. In connection with retinal hemorrhage, it is well to remember that in intra-ocular blood extravasation that cannot be otherwise accounted for, occuring in jjersons about the age of forty or after, such a sign should always suggest thorough examination of the blood pressure of the individual. To a certain extent, this same suggestion applies to so-called idiopathic subcon- junctival hemorrhage and oedema of the lids. AX EARLY RECUGXITIOX OF OCULAR AXGIO-SCLEROSIS IS VERY IMPORTAXT. These, then, are some of the signs of angio-sclerosis as seen in the eye, and as stated in the beginning, the gravity of the general disease process, and the necessity of an early recognition and treatment thereof, warrant a close examination for such changes in the fundi of all persons coming to us for refraction about or after the age of forty. By so doing, in a consid- erable number of instances, it will be possible to conserve the health and prolong the life of patients wiio themselves are altogether unconscious of the serious malady at work within their bodies. A I'EW WORDS OX TRKATMEXT. In closing, a lew words in regard to treatment may not be amiss. The early detection of vascular sclerosis is, of course, of great importance, be- Papc 27.; RAXSOIfOFF MEMORIAL VOLUME cause then the cause can be sought and an attempt made to prevent its further action. The very nature of the disease, from the standpoint of causative factors and pathology, necessitates emphasis on the hygiene of h'ving. The life which is indicated to be led by such patients should be one of moderation in work, in eating, in exercise, and in personal habits of life; with emphasis on elimination by bowels, kidneys, skin, and respiratory tracts. Proper drugs have their place, especially the iodides for their alterative and resorptive effects, while symptomatically the nitrites and sedatives, like the bromides, may be of value. The digitalis and strychnine groups can also be called upon if the heart condition indicates their exhibition. But in any rational therapy, the elimination of the underlying causes of the sclerosis are, of course, of the greatest importance, and in conjunction with the above measures, cannot be too much emphasized. BIOLOGIC ASPECTS OF DEMENTIA PR.ECOX.* F. V\'. Langdon. M. n. Cincinnati. When the penius of Kraepelin — genius heing here, as usual, simply a synonym for a high order of painstaking work — "merged," under one name. a group of psychoses characterized in common, by development in adol- escence, emotional apathy, poverty of thought, inadequacy of volition, and progressive or intermittent deterioration, he conferred a lasting benefit on the student of mental disorders and the sociologist. This "master stroke of a master mind." however, did much more than furnish a convenient formula for diagnosis and prognosis ; it suggested at once the possibility of a common cause or causes for the disease process ; and presented for solution the problems of its possible biologic significance and pathologic interpretation. In brief, what does it mean in terms of normal and perverted life? These deeper problems are not only important — they are of I'ital iinpor- tance — to the civilized nations of the earth as well as to such as may attain civilization in the future. Their consideration therefore is timely, partic- ularly to us of the United States of .Atnerica. the "melting pot of the nations." where "preparedness" is the watchword, and may be the price of continued liberty of. and government by, the people. To illustrate this point of view, we have only to realize that one-fifth of the total discharges from our army in 1912 was for mental disease (not including neurasthenia and hysteria). "The discharge rate for mental dis- ease per 1000 was 2.64 ; higher than for any other class of disease ; tuber- culosis, including all its forms, being next with a rate of 1.56 per 1000."' The same writer states that "more than half the mental diseases with which we meet in the United States Army, requiring asylum treatment, are of the one form, dementia prsecox." Now. if our present army, composed of picked material of a "good" physical and mental standard, develops 2.64 per 1000 of cases of mental dis- ease per year, what may we expect of the "1,610,600 men available for mili- tary duty," in the state of New York for instance, according to the report of the adjutant general of New York in 1915?' Were these organized into a military body, the number "weeded out" in one year on account of mental disease, based on the above figures, would be 4250; more than four full regiments "killed" without firing a shot ; and of these more than tivo whole regiments would be victims of dementia prsecox. It is evident that these figures, based on a proportion of 50 per cent, of dementia pr?ecox in admissions from the army, to the Government Hospital for the Insane, are higher than those of the general population, which range RANSOHOFF MEMORIAL VOLUME from 15 to 25 per cent, in different states. liut it nnist be remembered that the army is recruited from "picked" material as regards age as well as physique and mentality, and consequently consists of men of a "dementia prpecox age," in much greater proportion than does the civil population. There is no reason to bcheve that the situation in Eurojiean armies is any better — if as good. It is not only the material for armies that is invoked in the question of dementia pr.TCox, but the general population at a most productive time of life. It must not be supposed, however, that we of the United States of Amer- ica are alone in facing this problem. Our friend and fellow-member of this association, Dr. Frederick Peterson^' of New York, writes me: "Dementia prrecox is probably as common in Japan as elsewhere." This opinion is based on his own extensive observations in that country. He also writes me :* "I saw cases of dementia prsecox among the native Fellaheen in Egypt. . . . I remember perfectly a typical case in a Sudanese negress." H I! Sto.liUit ) Fig. 1. Chimpanzee: Hand showmg flat thenar emnience and ['ad of thumb directed forward. (Compare Fig. 4.) My friend Dr. S. Lilienstein, ' of r>ad Nenheini, German, a psychiatrist of large experience in Germany and the Orient, also informs me that — In China and Japan in general there are the same kinds of mental diseases as in our asylums (of German). In Japan ... I saw, for instance, many cases of hebe- phrenia or dementia pra-cox, imitating the voices of animals, and it was explained to me that they fancy themselves to be "bewitched" into beasts, wolves, dogs, or hens. In connection with the foregoing we must remember that the Egyptians represent the remains of one of the oldest civilizations, in a state of regres- sion, while Japan is an example of an also ancient civilization, which has taken on within a half-century most tremendous evolutionary stride. The case noted in a Sudanese negress, by Peterson, near the otlier point of the scale, indicates that dementia prsecox is not necessarily a disease of higher civilization, while it may be more common in such. The biologic significance of the foregoing may be postulated, for our present purpose, as follows : (1) The efficiency in the "struggle for existence'^ of races and nations will be adversely affected in proportion to the mentally deficient of all types, Page 2-.e F. IV. LANG DON contained in their populations. Of these dementia praecox is of the greatest importance because of its numerical preponderance and of its incidence at the most ambitious and productive period of life, when the foundations are being- laid for the highest achievements of the race, as well as its per- petuation. Hence, the chances for supremacy, or inferiority, or even the very exist- ence of a nation or race, may hinge, in the future, upon its proportionate pop- ulation of subjects of dementia prsecox. Turning from these matters of racial and national biologic bearing to those of individualistic significance — what evidence have we which may throw light on the fundamental nature of dementia praecox ? Three views are current with respect to the underlying processes of the disorder, which is evidently more than a mere psychosis. First : That it is due to some unknown toxin or toxins of specific char- acter to this disease and producing no other. Such toxin may act directly on the nervous mechanism through the nutrient fluids or indirectly by disturb- Fig. 2. Chimpanzee: Hand showing non-rotation of terminal phalanx of thumb. ilnring flexion. (Photo, by Dr. W. H. 11. Stod(7(/" of thumb directed forward. functions, those of defence and ofifence, of the hunter, the fisherman, the artisan and the artist ; and finally in the higher races, it has developed into an "organ of expression" second only in importance to the facial and ocular musculature. As such organ of expression it is not only an important adjunct to spoken language in the orator, the actor and the "man in the street," but has even replaced spoken language successfully in the deaf-mute, and more or less efficiently in communication between alien peoples. Its importance in human affairs is recognized in such current expressions as : "The Hand of God" ; "the hand, the servant of the brain" ; the "minister of reason and wisdom" (Cresollius). We speak of an unusually useful person as "handy to have around." It is not strange, therefore, that in its numerous variations and deficiencies some should tend to be atavistic in type, or indicative of incom- jileteness in an evolutionary sense. Comple.vity of function implies a correspondingly complex development in structure in any organ ; and as the hand is readily accessible to observa- Paoc in:i RAXSOHOFP MEMORIAL VOLUME tion, it is natural that the attention of astute clinicians should have been attracted to its pecularities in the subjects of various psychic anomalies. In civilized life, the handshake is to be viewed as a motor expression of emotional feeling; and as such, of varied characteristics, from the mere formal "touch" of the finger-tips to the hearty hand-grasp of the warm friend in expressing his pleasure at meeting you after a long absence. As an organ of emotional language it is natural that its motor "expres- sions" should be listless and defective in dementia prsecox subjects ; and we lind that this is the case. Kraepelin/- in his lectures, repeatedly calls attention to the peculiar mode of response of dementia ]ir?ecox patients to the ordinary salutation of ottering the hand. 'J"o cjuote from his clinical lectures ; "... I may call your attention to the fact that, when you olTer him your hand, the patient does not grasj' it, but only stretches his own hand out stiffly to meet it. Here we have the first sign of a disturbance which is often developed in dementia prwcox in a most astounding way." Again, in his 8th Edition,'-' he mentions the "hand-shake" as "cold, clammy, lifeless, heavy, exerting no pressure." The present writer in demonstrating these peculiarities in his clinics has referred to this "physical sign" as "the Kraepelinean hand-shake." It evi- dently deserves to rank as a physiological stigma of importance. To Stoddart," however, is due the great credit for discovery of certain pecularities of a structural character in the hands of dementia prsecox sub- jects, which in a measure, may be correlated with this characteristic hand- shake. To this type of hand he has applied the designation "Simian" — for obvi- ous reasons. For some of the illustrations of it accompanying this paper the writer is greatly indebted to the kind courtesy of Dr. Stoddart. They are reproductions of photographs taken by himself. This type of hand may be described as follows: /■. IV. LANGDON THE SIMIAN TYPE OF HAND OF STODDART. ( 1 ) With the hand open, the fingers and thuml) fully extended and the inter-digital spaces closed — the palmar surface of tJie thuuib faces forward — on the same plane, or nearly so, as the palmar surfaces of the lingers. ( In the normal hand, the palmar aspect of the Ihunib faces at a right angle to that of the fingers or nearly so.) (2) When the thumb is flexed its teniiiiial phalanx does not rotate inward — or does so in a less degree than usual. (In the normal hand it does rotate inward, thus contributing to greater accuracy and power of a])position of thumb and finger tips.) (3) The fingers are markedly hyper-exleiisible at the metacarpo- phalancjeal joint. In some instances they may be "sent backward" to a right fPhoto. I.y n.. K. A. Xoilh.l Fig. 6. Dementia prifcox ; Shi)vviiii> li\ pcr-cxtcnsililc lingers at Metaearpo-plialan- Seal joints. angle with the metacarpus. ( This peculiarity is also noted in many grown imbeciles and in young children, as well as in the subjects of dementia prjecox.) Since the increasing complexity of structure and function of the hand in man is determined and dominated by a corresponding com])lexity of the cortex cerebri — it is not difficult to correlate a deficiency in hand-structure and function with lack of cortical evolution. Stoddart'^ comments on these manual stigmata as follows: These characteristics, taken in conjunction with the facts that they are sometimes encountered in cases of idiocy, especially those of the Mongol type, that imbeciles are liable to develop at puberty symptoms resembling those of dementia praecox, and that the above peculiarities of the hands are also to be observed in the chimpanzee, all points to the conclusion that dementia praecox should be regarded as a failure in evolu- tion, as an atavism or reversion to an ancestral type. Nevertheless we are bound to admit that atavism does not entirely account for all the features of this disease. The rapidity of the deterioration, the physical ill-health and the possibility of recovery, though rare, all indicate that some active morliid process is at work. Page SRI RAXSOHOFF MEMORIAL rOLl'MF It is apparent from the foregoing that Stoddart inchnes to view dementia l^rjecox as a specific disease process developing upon a foundation of sub- evolution or atavism. Numerous other stigmata of degenerative significance are present in dementia pr?ccox, as those of the face, jialate, auricle, etc., but these are common to the subjects of various psychoses — and not es])ecially charac- teristic of dementia precox. Hence they do not come within the scope of this paper. A review of the literature and observation of the diagnostic methods of many psychiatrists, has led the present writer to conclude that these "hand stigmata" are overlooked by a great majority of clinicians — or not given due weight as diagnostic and prognostic indicators. His personal experience has convinced him of their decided value as factors in diagnosis, especially in that "doubtful" class of cases, sometimes labelled "undifferentiated" — with a prefix of "depression," "elation," , 'hallu- cinosis," etc., as the case may be. They are also often of value as guides, in very early stages of dementia prsecox ; and due consideration of them may make us more guarded in our prognosis in the presence of apparently "mild," "psychic departures." Some indication of the frequency of occurrence of the "Simian type" of hand in dementia praecox may be of interest in this connection. My asso- ciate, Dr. Emerson A. North, has kindly investigated fijr me a total of forty-four cases, taken consecutively, without selection, in two institutions in Ohio. His results follow: Simian stigmata: Typical (-|--|--f) 21 Partial {++) 14 -Absent 8 *Dou1)tful 1 44 The cases classed as "typical" present the three chief "stigmata" well developed ; namely : Thumb facing forward ; absence of internal rotation of its terminal phalanx ; hyper-extensile fingers at metacarpophalangeal joint. Those classed as "partial" presented only two of the "stigmata." In thirty-five cases of forty-four, practically 80 per cent., the stigmata were such as to be of clear diagnostic value. By way of contrast we may note that the "Simian hand" is rarely seen in typical manic-depressives. The writer has seen a number of patients with "Simian" hands, diagnosed as manic-depressives by experienced alienists and has so diagnosed some others himself — on the basis of mental symp- toms; but subsequent observation of these patients has shown the original diagnosis to be erroneous, and the course of the disease that of dementia prcvcox. In addition to the "hand-shake" of Kraepelin, already mentioned, the "snout cramp" of Kahlbaum, noted by Kraepelin, the "shut-in personality" ♦Observations not truswortli.v by reason of extensive deformity o: hands by cicatrices of old burns. Page SS2 F. IV. LANGDON of Hoch, the "special make-up" of Adolf Meyer, and other physiological observations, might come up for consideration as of biologic significance, but they are already so widely known and discussed that a mere reference to them is sufficient. Recently, however, mention has been made of a "sign" of possible biologic bearing, by Steen,'-' which consists in a characteristic sitting attitude, noted by him as "frequent" in dementia ])raecox subjects and described as follows; The arms are held close to the trunk, with, as a rule, the elbow joint in a condition of stiff extension; the hands pronated and resting on the lower part of the thighs, or even on the knees. . . . This attitude is possibly an example of reversion, and is seen in the statues of ancient Egypt. He therefore calls it the "Ancient Egyptian attitude." Finally, as we go about our daily duties, we all recognize the dementia praecox "make-up" as a practical clinical entity, which fact of itself is sug- gestive of a basis of biologic significance. The view, based on results of the Abderhalden dialysis method, that the disease is an "endocrinopathy" depends on evidences of various morljid pro- teins in the content of the blood serum. The view of Orton"' on this subject may be here ]M-esented as that of a competent critic — F.ven if we accept the theory and the results of its most hopeful investigators, we are only brought to the beginning of a wide field of investigation ; as by the interpre- tation of the theory, the results speak only for a faulty metabolism in specific organs and as yet give no light on the underlying causes, i. e., the fact that the metabolism of the testicle and brain are disturbed gives no insight into the cause of such disturb- ance. To the present writer it would seem quite conceivable that the indica- tions of wide-spread defects in various organs and their premature degen- eration — even if established, are also logically attributable to general defi- ciencies of "make-up" and consequent undue susceptibility to infectious or other disease agencies. In other words, they may argue in favor of a bio- logic or basic defect. To sum up : (1) In the interpretation of the role of the biologic factors in this psychosis, so far as the evidence available at present permits, we must recog- nize the fact that, in the subject of dementia prsecox, we have to deal with one of the "by-products" of the "Laboratory of Nature," an organism inade- quate to adjust itself to its normal environment, owing to an arrest of evolu- tion and a premature and irregular involution. Such an organism may be likened to a "proper soil." Not every yoittli therefore can develop a dementia prcccox form of break-down of the psychic mechanism. (2) The clinical course of the disease, and the findings of Southard.' suggest destructive agencies, which may influence the rate and amount of "deterioration." Here the "specific disease" element must be considered as a possibility. Such element may be viewed as playing the role of a noxious Page 3S.i RAXSOHOFF MEMORIAL VOLUME weed, or destructive parasite, damaging; the immature mental "crop" already started. f3) Psycliogeiiic factors (situations, conflicts, etc.) may quite plausibly he likened to "the seed." determining the character of the subsequent "abnor- mal crop." /. c, the "form and content" of the psychosis, its "trends" and other psychic activities. CONXLUSIOXS. The mere presentation of evidence of the nature of a disease is obviously of litlle practical value in itself. To be fruitful in results it should point the way to constructive lines of thought. What useful lesson may we learn from a study of these various biologic asf^ects of dementia pnecox? Since "mind" in its complete expression, includes the end results of all reactions of the animal organism to its environment, it is obviously impos- sibl»^ to draw a sharp scientific line of demarkation between psychology and psychiatry. The phenomena of the two sciences may be said to represent merely difTering results of "rustling of the leaves" on the higher branches of the "tree of biology." Our distinctions therefore are often arbitrary, based on the expediency of social conduct. Hence they may vary in different races and in the same race at different stages of development. The same truth applies to individuals. Any practical plan of theraiiy for dementia pra?cox should recognize the biologic tripod of sith-evolution. ncuro-toxccmia. and faulty psycho-genesis as the probable basis of the disease. Our efforts therefore should be directed toward improving the "soil." remo\al of "weeds" and changing the "crop." The obvious indications are. (a) removal of the patient from sources of "psychic-conflicts" and "difficult adjustments" at as early a stage as possible. This means, of course, in practically every case, removal from home and home influences; (b) rest, physical and mental. /;i bed. during the acute stage, so that the physiological energies may be conserved and resistance to the toxic element may be promoted; (c) attention to anemia and other mor- bid blood states — if a leucocytosis could be induced it would probably be desirable in some cases; (d) eliminative measures by hydrotherapy and otherwise are very important; (e) nutritional and constructive agencies must be pushed to the limit. As general health and well-being improve under this course, moderate exercise in the open air and suitalile occupational and diversioiial therapy become useful. The difficulties of productive psycho-analysis and psycho-therapy are obviously great, in the fully developed psychosis, but their possibilities in very early stages of the disease may be correspondingly great. Under the above outlined methods of management, some cases improve so as to be able to resume family and social life to some extent; others rank in statistics as "recovered," though it is probable that they would be more correctly labelled "recovery rvith defect." It is conceivable, however, that in exceptionally favorable subjects, in an early stage of the illness, under the Page 2&k F. IV. LANGDON modes of management just outlined, tlie neuro-toxic element of the disease may "run its course," leaving a minimum of deterioration : and that (he dynamic impulses of a beneficent nature, latent for a time, now relieved of their handicap, may reassert their powers. Evolution may then go on to a fairly normal completion — for that individual. These are the cases that may he said to really "reco\cr." They are rare, hut they encourage us to try and to hope. KEFERENCES. 1 Kinf. Captain Kdgar. M. C. V. S. A ,. : Mental Disease a ml Defect in fnil cl Stat Troops.' War Dept., Office of T he Surgeon Cenei -al. Bulletin No. 5. M arch. 19M. N. Y. Times: Kditori al. May 17. 1916. 3. Peterson, Frederick, N . v.: Personal , lommunication Februa ry 4. 1916. 4. Ibid.: Febrnary 12, 1916. 5. Lilienstein, S.. Bad N: luheim. Germany: Personal communica tion, March 6, 19li 6. Kraepelin: Psychiatric e. 1913. 7. Southard, K. E.: On the Topographical Distribution of Cortc ;x Lesions and .Am jmalies iu Dementi ia Pncco.x. with Some Ac count oi their Fui ictional Significance. Amcr. Jour. Insanil :y, LXX 383, 603, October, 191-)-Jani,ary, 1915. 8. Meyer, Adolf: The I )vnamic Interpret ation of Dementia Pi •iccox. Amer. Jour . of Ps y chology. XXI, July, 1910, 385-403. 9. lloch, August: Const ;itutional Factors in the Dementia Pr: ecox (Iroup. Rev. .\cur. S Psych., Vni, August, 1910, -163. 10. Ouoted bv Hoch: Rei new of Bleukr's Schizophrenia. Rev. of Neur. & Psych.. X. Jun e. 1912, 259" 11. Campbell, C. Macfie: A .Modern Con iception of Dementia Pr.ecox. Rev. of Xenr. & I'-sych.. Vll, October, 1909, 623. IT Kvaenelin. Emil: I.ec Uirt-s on Clinical Psychiatry. English tra.i-lation by T, ; c. N. V.,"\Vm. Wood & Co.. 190-4. . U. Kraepelin. K.: I'syrln .It, if, ,Stl, c.l, 19 13. u Stn,l,l.-,rt. W. II. 1!.: -Mi,„l and Us 1) isorders. London. 1908, 230, 231. Same 2nd e. 1.. .UX-.l.Vi. 1 ; SI.,,,, K, 11 : .\ CM; lr:,ctcristic Attitu, lie, etc. .Tour. Ment. Sci., Januaiy, 191 6, p. 17 9. (Ollot, , 1 1 , l;,v N\l,r. & P-y vh.. .March, 1916, p. 132.) 1... 1 ),!,,,,, S,,,ni,i-I -I',; -1 n.,- l',.-eut Stat, ..s of the .\ppl,cali,.n ..f the AberhaUIei , Dialy. ■ is .\letliod to ]■•. ■ ,!:■■ ^11,- , In a(|,l,ii. , :.. 1 ■ ■ •,. ■ .i.ful acknowlcdg ments a re due to my 1, :- .■ 1 ' w . 1 . rinan; to my Ors. Ji. A. \\,ll,,:,„. ,:,■,! I-,,,,,. '-.,.' \ .\.>,ili ,,,, , ;i)i,. ,ii .1,1.1 .I..II I., .i: .l..ta and some of the ilU is- trations ; to i>r, !■. U. H.irmon. 1.- ll..spilai, Ciiicnnaii . tor the courtesies of acce to the ' wealth of material conla lution, and to Dr. 11 . Douglas Singer f or valu. ed suggestions and PERNICIOUS ANEMIA WITH MENTAL SYMPTOMS OBSF.RVATIONS ON THE VARYING EXTENT AND PROBABLE nURATIOX' OF CENTRAL NERVOUS SYSTEM LESIONS IN FOUR NECROPSIED CASES.* Loi'is A. Li'iuK. M.A., M.D. Cincinnati r)iir lsy. — This was performed six hours after death. The body is that of a well built and nourished, white man, 176 cm. in length. The skin is waxy gray with a slight yellowish cast. There is a faint edema of the lower legs and some atrophy of the left thigh. The pupils measure 5 mm. in diameter and are equal. There is a superficial decubitus over the sacrum. Rigor mortis is faintly present. Page S'jr, RAXS OHOFF MEMORIAL VOLUME \'entral Section : The fat is lemon yellow in color and nicasnres 2 cm. over alnlo- men and 1 cm. over thorax. Tlie spleen is adherent to the external lateral surface. The appendix above the pelvic brim measures 7 cm. in length. The bladder is dis- tended and the intestines somewhat injected. The diaphragm arches to the fourth rib on the right side and to the fifth interspace on the left side. The gall-bladder is dis- tended and contains many stones. Thorax : The bone marrow is yellowish pink in the sternum. There is no free fluid in either pleural cavity, hut there are adhesions at the apex of the right lung. The pericardium is heavily loaded with fat. The apex of the heart is in the fifth mterspace. Heart: Weight, 453 gm. The epicardial fat is fairly abundant. The descending branch of the left coronary shows sclerosis. The right coronary and circumflex arter- ies show constrictions with calcifications. Every valve is thickened, particularly the aortic which shows distortion of the cusps. There are some vegetations which are calcified around the origin of the left coronary in the internal surface of the aorta. Figs. 6, 7, 8 (Case 1.) Sections of the cervical, dorsal and lumbar regions of the .spinal cord. The degeneration of the posterior columns is marked. This degenera- tion is only moderately severe in the lumbar region, but becomes progressively worse in the upper portions of the cord. It reaches its climax in the cervical region. Here, the destruction is seen to be very severe. Within the area of degeneration, large, jagged holes are present. This is in marked contrast to tabes dorsalis. In the latter condition, the degeneration of the posterior columns, as a rule, is greater in the lumbar region than in the cervical region. The degeneration in the lateral columns, which as a whole is much less than in the posterior columns, increases in intensity from above downward. The posterior roots in the lumbar section show evidences of degeneration. The hole seen in the lateral column of each section has been made to mark the right side of the cord. This applies to all the following photographs of the cord. Weigert's myelin sheath stain (X 10). The myocardium is pinkish gray in color and contains multiple white streaks measuring from O.S to 0,6 cm. in extent. Lungs: Weight — left lung, 385 gm. ; right, 1200 gni. The right lung pits on pressure, but is crepitant for the most part. There is a slight thickening of the pleura at the apex. The bronchi are reddened and show frothy fluid adherent to mucus. The left lung has a collapsed area in the lowest part of the upper lobe and in the posterior part of the lower lobe. Section of this shows it to be somewhat redder but not wetter than usual. The bronchi are reddened but the peribronchial lymph nodes are not enlarged. Page 200 LOUIS A. LURIE Spleen : Weight, 165 gm. There are two fetal lobulations on the lower border. The capsule is somewhat thickened and wrinkled. The pulp is red and watery, and letracts on section. The trabeculae are increased and the malpighian bodies are numerous. Adrenals : They are embedded in fat and are large. On section they show marked mottling of cortex and medidla with yellow and red. The medulla is scarcely to be differentiated from the cortex. Figure 8 Kidneys : These are deeply embedded in fat. The capsule strips with difficulty. Liver : Weight, 1800 gm., and has a yellowish pink color. The capsule is slightly thickened and there is a focal area of adhesion to the diaphragm. Section shows a fairly pale homogeneous substance. The gall-bladder contains forty-eight stones. Pancreas; The splenic artery is tortuous, markedly sclerosed and calcified. Every level of the pancreas examined shows fat replacement in varying amounts. Page Hit RAXSOHOPF MEMORIAL VOLUME Gastro-Iiitestinal Tract: Section of stomach shows the wall somewhat thickened and glossy. Xo rugae are present. Yellow mucus drips from the surface. There is nothing of note in the intestinal tract. Special Examination: The bone marrow of the left femur was inspected, and found to be raspberry red in color. Brain : The dura is very adherent, but not particularly thickened. The superior surface of the brain generally is firmer than normal. The convolutional pattern is rich. The pia mater is not thickened except slightly in the sulci over the vertex. Base of brain shows a small aneurysm in the middle part of the left posterior communicating artery. The fourth ventricle shows clear granulations. The brain weight is 1100 gm., which, according to Tigges' formula, shows a loss of 308 gm. The cord shows minute specks of translucency in the middle of the posterior columns. CoLLOiD.AL Gold Chi.orid Re.^ction. 1|2I.^14!SI6|7!8|9|10 Cortex r2'2'2'2'3'n'OiO Bloodv Right base 1 2 n 1 1 11 010 Bloody Left base Mil 1 1 imVO'O Bloodv Third ventricle* (1 II iMi II (1 (10 0' Spinal fluid 1 M , 1 M M M 1 1 1 (1 1 1 Pericardial fluid (HMMI 1 1 1 2 2 .^ Histologic Examinations. — IVeiacrt Sectinns — Left Motor Area ■ Macroscopicallv, one sees a cross-section of a very large blood vessel with thickened walls. Surround- ing it, in the medullary substance, is a very large area of softening which shades off gradually into the surrounding normal tissue. On microscopic examination, this area of softening is seen to be composed of destroyed nerve fibers, with here and there small patches of neuroglia and intact nerve fibers. The entire part appears cribriform owing to the presence of many large vacuoles, some of which have apparently run together to form large cavity-like spaces. In the medullary portion, the blood vessels are thickened, the perivascular spaces are dilated and in a great many instances there is a thinning out of the myelin sheaths in their immediate neighborhood. In many cases, this destructive action has gone on to complete degeneration so that irregularly circumscribed areas which vary in size and structure have been formed. Some are filled with debris and crossed by a few undegenerated nerve fibers, while others are clear and hyaline-like in appearance. At the bifurcation of one of the capillaries there is a so-called Lichtheim focus. In the cortical area the blood vessels are numerous and have very thick walls. Some are seen to be ruptured. The perivascular spaces are greatly distended. Internal Capsule: Here there are also vascular changes both in the gray and white matter. Many plaques of different sizes and shapes are seen surrounding the blood vessels. The perivascular spaces are uniformly distended. In a small portion of the medullary substance one can see a few of the miliary foci described by Preobrajensky. Pons : The most striking feature in this section are the miliary foci of Preobra- jensky. They are very numerous and confined entirely to the medullary portions and are most numerous in the center. Practically all are of uniform shape but not of uni- form size, some being three times as large as others. The smallest are about the size of small lymphocytes. They are fairly definitely circumscribed and have a punched out appearance. In many, an undamaged nerve fibril may be seen passing through the destroyed area. In addition to these miliary foci of Preobrajensky there are quite a number of well defined Lichtheim plaques. These bear a close relationship to the blood vessels. Cord : With the unaided eye one can see a distinct circumscribed degeneration of the column of GoU. In the cervical region, this has proceeded to apparent cavity for- mation. The degeneration, although still sharply defined in the thoracic region, becomes less and less marked as we pass to the lumbar region. The reverse, however, is true of the lateral columns. Here the degeneration, which is much slighter than in the posterior columns, increases from above downward. On microscopic examination, we see that the column of Goll is practically entirely destroyed. Several large spaces with irregular jagged edges are conspicuous. Smaller vacuoles are numerous. Here and there are evidences of small hemorrhages. The blood vessels are intensely congested. Cresylccht-Viotet Sections—Left Motor Area: The pyramidal cells appear shrunken and granular. Many of the pericellular spaces are filled with a large num- Page 298 LOUIS A. LURIE her of satellite cells. The perivascular spaces, especially those of the cortical area, are distended. Internal Capsule: Here and there are small islands of sclerotic tissue, apparently not related to the blood vessels. The pyramidal cells are uniformly shrunken, irreg- ular in outline, and in a great many, the nucleus is displaced. Some satellitosis is present. From one pericellular space, the nerve cell had entirely disappeared and its place is occupied by live satellite c^lls. Pons: Small, clear, oval areas corresponding in size and position to the miliary foci of Preobrajenskv, seen in the Weigert section of the pons, are also present here. In the gray matter there are many small patchy areas of degeneration. The nerve cells are not as noticeably abnormal as those of the preceding sections. Medulla : Pigmentation of the nerve cells is marked. The perivascular spaces are tremendously distended and filled with debris. Large areas of degeneration are present in the white matter. The pyramidal tracts are full of vacuoles. Two types of glia cells, diflering principally in size, were observed. The larger ones, in all probability, sirnply represent more mature forms. They are profusely distributed over the entire section, but more particularly in the region of the olivary nuclei. Cord : The posterior columns contain numerous thin walled capillaries which are surrounded by large amounts of glia cells and fibers. The glia replacement cells are of comparatively large size and of the stellate type. An occasional undegenerated or only partially degenerated nerve fiber is seen. The increase in the number of blood vessels is most noticeable in the dorsal portion of the cord. The nerve cells show various changes. Some are very much shrunken and irregular in outline ; others contain numer- ous variously-sized granules; still others are swollen and contain a large amount of yellow pigment. Pigmentation is present both in the anterior and posterior horn cells, but occurs more frequently and uniformly in the former. This pigmentation differs from that normally found in the cells of persons of advanced years, in that it is diffuse, somewhat granular and not clumped at one pole of the cell body. In these cells, the pigment is centrally located and apparently has pushed the protoplasmic substance to the extreme periphery of the cell. In some of the cells, the nucleus is displaced to one side and stains poorly. Case 2 (Necropsy 16-59). Historv.—C. C. a white woman, aged 54. Was com- mitted to the Boston' State Hospital, April 25, 1916, with the diagnoses of pernicious anemia and symptomatic psychosis. Family History. — Her mother died at the age of fifty of tuberculosis. Of six siblings, two have died of tuberculosis; one is now in a hospital suffering from tuber- cular trouble; one (a sister) is excessively alcoholic and has seizures with unconscious- ness, and one died in infancy. Personal History. — The patient was born at Salem, Mass., in 1862. Her education was limited but she was able to read and write. She drank a little beer and smoked cigarets for about a year. She formerly used snuff. Her sexual habits, as far as could be ascertained, were normal. She was never very cheerful, and many times greatly depressed. She was somewhat obstinate, but in many ways showed that she could be very sympathetic and kind. She was known to be hypochondriacal and appre- hensive. She was a good housekeeper, was sociable and made friends. Her first mar- riage occurred when she was eighteen years old. By that husband she had one child, who died at the age of three of "water on the brain." .\t the age of thirty-six she was again married, but by this marriage she had no children and no miscarriages. Since the second marriage she has led a very lonesome life. Medical History. — In childhood she was at the Salem Hospital because of anemia. According to the statements of her acquaintances, she has always been pale. She always claimed that she was a spiritualist and "could see dead people." Early in 1915 she went to the Eye and Ear Infirmary because she thought that she had cancer of the throat. In May of that year she was for nearly three weeks a patient at the Massa- chusetts General Hospital with what was diagnosed as pernicious anemia. At that time she was irrational and had visual hallucinations. She saw animals and would point her fingers at imaginary objects. She walked unsteadily and fell frequently but never lost consciousness. Sometimes she had complete loss of vision for a few min- utes. Until a year previous to this attack, the patient was able to do her housework. Six weeks ago she became much worse ; very excitable, swore and used obscene lan- guage. Recently she carried on an imaginary conversation with her deceased daugh- ter. She has also turned against her niece and niece's little girl of whom she has been very fond. On occasions she would "jump out of bed at people." There were no homicidal or suicidal tendencies. Physical Examination. — The patient was a well developed and well nourished woman of fifty-four. Her face was of a striking pallor with a lemon yellow tinge. Page SaH RANSOHOFF MEMORIAL VOLUME The mucosae were very pale. There was a harsh systolic murmur at the apex that was transmitted upward to the axilla. The liver was enlarged hut not tender. The spleen was palpahle in the left hypnchoiidrium and the dullness extended to 3 cm. above the umbilical line. The blond pressure readings were: systolic, 105: diastolic, 45. Neurologic l'..rniiiiiiali"ii_ — TIk- pupils were equal and regular. They reacted well to accommodation but xery sluguisbly to light. There was no nystagmus or strabismus. The tongue protruded in the midline and appeared very anemic. The arm reflexes were all hyperactive. There was hyperesthesia of 'the lower extremeties. The knee jerks were equal but sluggish: the Achilles active and equal, and the plantars hyper- active. No Babinski, Gordon or.^Oppenheim reflexes were obtained. There was no ankle clonus. A formal mental examination could not be made on account of her mental state. The patient appeared to be in a dazed, half asleep state'. It was difficult to get her to comprehend questions, but when her attention was gained she usually answered the questions fairly well. \\ hen asked where she was born, she delayed before answer- Fig. 9 (Case 2). Weigert's myelin sheath stain of left motor area showing small foci of degeneration and one larger area in intimate relatiousliip with the neighboring blood vessels. ing, then asked what the question was. Slie finally said that she was born in Salem. She did not know how long she had lived there. She answered questions as if very weary and gave the impression that the incorrect answers were due, in part, to lack of effort. She persisted in the feeling that her niece had intended to injure her and refused to see her. Her condition gradually grew worse and she was less and less easily aroused. Twelve days after her admission, she died. Wassermann Reaction : Serum, negative. Blood Examination: Hemoglobin less than 10 per cent. ( Sahli I ; color index, 1.6; red blood cells, 780,000; white blood cells, 4,700; polymorphonuclear leukocytes, GO per cent. ; small lymphocytes, ,32 per cent. ; large lymphocytes, 8 per cent. The red blood cells showed marked anisocytosis and poikylocytosis, and some achromia. There was a large number of microcytes and macrocytes. No stipling or nucleated reds were seen. A later blood examination showed hemoglobin less than 10 per cent. ( Sahli ) ; red blood cells, 550,000; white blood cells, 4,500; polymorphonuclear leukocytes, 01 per Page .100 LOUIS A. LURIE cent. ; small lymphocytes, 34 per cent. : large lymph, eosinophils, 1 per cent.: mast cells, 1 per cent. T\v were seen. The red blood cells shuwcd iii.irkdl \ were very many small cells Init tin- inai'ini\ w . i r index was increased. There was n.. aclnniiii.i aii'l sional cells showed marked polychrcjinalophilia and < ' tipling \ I l^^\ Pi iln )/— The body wrman 1S7 cm m length F i,,( r i are palpable The skm is km n \ 1 SIX hours after death Tli | ii| 1 Ventral Section The il 1 nm: fat being bncht lemon m11 w I li i-tes. 3 per cent.; transitionals, 0: norninlilasts and one megaloblast lain III 111 '~i/c and shape. There irrii,\tis ,ind tile aMTagc volume asioiial cells showed very marked s that of a well developed pi3rl> n urished rtis is not present No superhcnl hmph nodes i\ 111 color The necrops^ was perf irincd thirty- |im1 and regular and 4 cm m dnmcttr. I It IS bright ^ellow the thoracic an 1 mental \ I 1 12 tm lelrw the ensiform nrtilage. The Fig 10 (Case method ffere midullarv substan spleen is not encased in adhesions. The appendix is retrocecal and adherent to the cecum. The diaphragm arches to the lower border of the fourth rib on the right and to the lower border of the fifth rib on the left. Heart: The myocardium of left ventricle shows tiger lily striations with here and there translucent areas. The muscle is soft. Lungs : These are encased in adhesions. The cut surface is grayish brown in color at the apices. In the lower lobe it is pinkish-yellowish-gray. The connective tissue element is well marked. A frothy, grayish fellow, thick fluid is scraped from the cut surface. Abdomen : The spleen weighs 185 gm. and is of firm consistency, with a shiny surface. It is purplish brown in color. The capsule is not thickened; the trabeculae are prominent and the nialpighian bodies appear as pin points. Kidneys; These showed cystic areas on the lateral edge. The capsules stripped easily. Liver: This weighs L560 gm. It is shiny, mottled and of yellowish-brown color. The capsule in general is not thickened. It is of firm consistency. Pancreas: Pale; otherwise there is nothing of note. Gastro-lntestinal : The stomach is pale, glassy and atrophic in appearance near the cardiac end. Head; The skull tables show a symiiu-lrical tliickening. There are slight patches of endostosis in the frontal region. RANSOHOFF MEMORIAL VOLUME Superior Surface of Brain : There is no apparent atrophy and it is firm to the touch. There are inequalities between the first and second frontals and between the right and left prefrontals. Base of Brain : The basilar artery is small and no sclerosis in the circle of Willis could be seen. There is a slight thickening of the pia around the third nerves, otherwise the cranial nerves show no abnormalities. The mammillary bodies are flat- tened. The brain is pale. The fourth ventricle is clear. A pressure ring cerebellum is noted. In the left base the fluid is yellow. This also applies to the corte.x. How- ever, neither the right base nor the third ventricle showed this condition. The spinal fluid was mixed with blood. The brain weighed 1,175 gm., which according to Tigges' formula gives a loss in weight of 81 gm. Colloidal Gold Chlokid Reaction. ~" 1|2|3| 4|5|6|7|8!9|10 Cortex 4|S15|5|SI3|3|2|1 1 Left base 4!4\Si,T 5 5'.' ! i r n Right base 1;4',^ ^ .\ -? } ; _' 1 Third ventricle (blood stained) oio'i 1 iJ :• 12 1 Spinal fluid (blood stained) O'O'l 4 - ^ ^ \ ^ ^ '• Pericardial fluid O'Oii 1 _',^ .= r- ? ,1 Histological Examination. — Weigert Section — Left Motor Area. — Small foci of degeneration resembling those described by Preobrajensky are noticed in the subcort- ical region. These, however, are not numerous. There are also some larger areas of degeneration that are in close relation to the blood vessels. The cortical perivascular lymph spaces are distended and here and there are asso- ciated with small areas of degeneration. Pons : Here we also see miliary foci of Preobrajensky. Init these, unlike those described in Case 1, are more numerous in the peripheral portions of the medullary substance. The myelin is thinned out in many places and in many instances this has gone on to complete degeneration. Three Lichtheim plaques were counted which were in intimate contact with the blood vessels. In addition, two sharply defined areas of degeneration, involving entire tracts, are present. These are also seen in the sections of the pons stained with cresylecht-violet and are more fully described under the latter heading. The gray matter showed practically no involvement. Medulla: The white matter showed but slight involvement. Discretely scattered between the fibers of the raphe were small foci of degeneration. In the gray matter, however, it was not uncommon to come upon distinct areas of degeneration in the neighborhood of blood vessels. This was especially true of the dorsal portion of the medulla. Cord : In the left lateral column of the cord, in the cervical region, there are several foci of the Lichtheim type. The blood vessels which are rather numerous have greatly thickened walls. In the lumbar region, there are patchy areas where the myelin is thinned out. The gray matter appears normal. Cresylccht-Violct Sections — Left Motor Area. — The pyramidal cells, especially those in the outermost layer of the cortex, are shrunken and irregular in outline, the nucleus, in many cases, being crowded to one side. In others it is entirely absent. Satellite cells are numerous. Large stellate glia cells were observed. The blood vessels are numerous and the perivascular lymph spaces are uniformly distended. The sub- cortical area shows no large areas of degeneration, but here and there a few small, clear areas. Pons: Here we see many evidences of a pathologic process. In the medullary sub- stance there are numerous sievelike areas. Here the destruction of the nerve fiber.s has not been accompanied by any considerable increase in the neuroglia fibers, thereby producing the cribriform appearance. One also notices large sclerotic areas which apparently are c..niii.,M(l entirely of neuroglia. These hyaline-like areas involve entire tracts and ,ii( (Ir!iniiil\ circumscribed by fibers of other tracts which evi- dently have escaped lie hil; iiufilved in the destructive process. Furthermore, these sclerotic areas arc >\ niiiu irn ally distributed on either side of the pons. In addition to the areas just described, there are numerous perivascular areas of degeneration. These vary in size and have no definite margins, but shade off insensibly into the surrounding tissue. One of these perivascular areas of degeneration extends into a small collection Page SO'l LOUIS A. LURIE Fig. 11 (Case 2). Another section of the pons. Note the uneven deniyelinization of an entire tract. The destruction has progressed very far in the center vifhere large sclerotic areas have been formed. Compare this photograph with Figure 12, which is the same area stained with cresylecht-violet. RAXSOHOFF MEMORIAL VOLUME of nuclear cells which also show evidence of pathological involvement. They are irreg- ular in outline. Many are shrunken and granular and some show a diffuse chroma- tolysis. In the larger collections of gray matter, the perivascular spaces are distended and here and there one sees a patchy area of degeneration. These, however, are not numer- ous. The majority of the nerve cells show more or less changes. The axonal type of degeneration was observed. m^. Kis. 1- Case l'). Same area of pons as in Fii;ure 11 st This also shows the uneven degeneration of the entire tract of degeneration are seen. (X50.) Medulla: In the white matter, there are streaky patches of degeneration. Vacuo- lization is pronounced. The pyramidal tra(t'~ Avw no changes. Very few of the nerve cells appear normal. The majority are liiulil\ t;r.imilar and show more or less displace- ment of the nucleus. Clear areas, that appear like rifts in a cloud, are scattered about. Cord : Many irregular, pale areas, containmg necrotic tissue and surrounded by neuroglia, can be seen in the lateral columns. In some cases, the neuroglia cells seem to be clumped together. This is also met with but to a much lesser extent in the pos- terior columns. The cells of the anterior horns are bizarre in shape and contain yellow pigment, similar to that described in the preceding case. Case 3 (Xecropsy 18-34). History.^ — J. H., a white boy, aged 6 years and llj-i months, was admitted to the Monson State Hospital, January IS, 1917, with the diagnosis of epilepsy. 'This case will be icpoitcd iiiojc fully in a laK-i iiapui. LOUIS A. LURJE family History. — Father and mother are living and well. The father was 36 and the mother 34 years old at the time of the birth of the patient. The patient is one of sexen children. One older lirother. who was an epileptic, died. There is no other his- tory of insanity or feeblemindedness in the family. .An older sister of the patient died of pneumonia, aged two months. Three older brothers are living and well. The oldest, howexer, had conxulsions when teething at one year of age and had four convulsions -, l''i(i, iiiiioal liiid- Fig. 23 (Case 4).- — .Another view of the cortical motor area showing disintegration of the pyramidal cells, and distention of the pericellular spaces. Some of these cells are pale, shrunken, irregular in outline, stain poorly and unevenly, and show eccen- tricity of the nucleus. The severe neurogliar reaction is evident. In the lower right hand corner of the field, note the large sclerotic area surrounding a blood vessel. Cresylecht-violet stain. ( X 50. ) ings of pernicious anemia were present in the blood and especially the nucleated red blood cells. Early in April he failed rapidly and died on .April 15, without showing any new development of his disease. Necropsy. — Protocol (16-52). ^Necropsy was performed two hours after death. The body is that of a white male, 168 cm. in length. The skin is pale lemon yellow, especially over cheeks, forehead, and arms and legs. There is considerable pigmenta- tion over the back, chest, face and lower abdomen. Rigor mortis is present in jaws and legs. The lymph nodes are not palpable. The pupils are equal and measure 0.4 cm. in diameter. The eyeballs are slightly softened. The teeth show Riggs' disease. Ventral Section : The fat over the abdomen is pale yellow and moist. The muscles are red and mixed with apparent fatty streaks. The lovver border of the liver is 1 cm. below the ensiform cartilage. There is a slight amount of free fluid in the flanks. The appendix is 8 cm. in length. The tissue in the pelvis appears bloodless. The spleen is surrounded by adhesions. The diaphragm arches to the third rib. Thorax: The sternal marrow is richly red and somewhat fluid. There is a free fluid in the left chest and the pericardial sac is thickened. Page Sli LOUIS A. LURIE Heart : The epicardial fat is abundant and there are milk spots on the posterior surface. The heart muscle shows white mottling and also minute hemorrhages in the right auricle. It fragments easily. Lungs : They show very little of note. Abdomen: The spleen is grayish red and its capsule is slightly withered. A sec- tion shows the pulp to be red. It measures 10 by 5 by 2 cm. .\drenals : These are small and softened. Kidneys: There is an excessive amount of fat around the kidneys which are yellowish brown in color. The pyramids are white and poorly differentiated from the surrounding tissue. Two cysts containing fluid are seen. Liver : There are slight irregularities over the surface of the liver which is yel- lowish red in color. ,\ section shows packing together of the lobules. It measures 23 by 16 by 7 cm. Pancreas : This organ is dotted with hemorrhages. Gastro-Intestinal : The stomach is large and contains some fluid. The mucous membrane of the stomach is shiny. Brain: The dura shows signs of absorption in the frontal region and of thicken- ing along the longitudinal sinus. A slight amount of yellow fluid escapes on section of the dura. Points of hemorrhages are seen in the pia mater which shows some thickening along the vessels. It is held up from the cortex by fluid in the motor regions. The brain appears \ellr>\vish white. The right lobe sags, being apparently slightly shorter than the left. The pattern of convolutions is more nearly circular over the right lobe than over the left lobe. The brain has a resilient feeling. From the basal aspect, it is noticed that the pia is thickened over the pons, left third nerve, and optic chiasm. The left temporal tip is softer than the right. The left cerebral artery is larger than the right. The fourth ventricle is clear. Colloidal Gold Reaction 1I2!3|415|6|718|9J_10 Right base .0 1 i'l H» OlOlO Left base ^ ... . .^ ........ .. .(mmi n i u mHO Third ventricle* I M i (MilMl DiKVO Spinal fluid Oil (MHIOU 0|0 Pericardial fluid .. .^^. . . .0 i»'(Hi(HMro'0'0 * Slightly bloody. Histological Examination. — U'ciycrl Scstion — Left Motor Area. — The medullarv substance shows little of note. Ther are a few areas where the myelin has been com- pletely destroyed and also a few places where there is a thinning out of the myelin. Paralleling the edge of the cortex, there is a narrow strip of tissue which stains less heavily than the surrounding tissue. Under high power, this area is shown to contain small irregular shaped spaces which for the most part are structureless. A few are crossed by undegenerated or only partially degenerated nerve fibers. In this area, furthermore, the capillaries are very numerous and the perivascular spaces are distended. Pons : Here we see large foci of destroyed tissue in intimate relation with the blood vessels. It is almost possible to trace the entire process of their formation as they are present in all .stages of development. One notices first, a sliglit thinning out of the myelin sheaths in the immediate neighborhood of a blood vessel. The process continues and this thinnned out area becomes sievelike, due to the lack of uniformity in the destruction of the myelin sheaths. In the meshes of some of these cribriform areas, red blood cells are found. In the more advanced places, there has been an increase in the neuroglia with resultant formation of large plaques of sclerotic tissue. In one part of the field, the miliary foci described by Preobrajensky were also ob- served. Medulla: Small ragged foci of destroyed tissue, irregularly distributed are seen. The perivascular spaces of the blood vessels in the olivary nuclei are markedly dis- tended. Cord: (Cervical region.)— In this region, there are numerous small foci where the myelin sheaths have been destroyed with subsequent vacuolization. This destruc- tive process has occurred principally in the columns of Burdach. The columns of Goll are but slightly affected. The direct pyramidal tracts show more or less degenerative Page SIS RANSOM OFF MEMORIAL VOLUME changes also. (Dorsal region.) — This region appears practically normal. In the gray matter of the anterior horns one can see several small hemorrhagic areas. This is also present in the lumbar region which otherwise shows nothing of note. Cresylccht-Violet Sections. — Left Motor Area. — The cortical region shows exten- sive pathologic involvement. There is a tremendous overgrowth of neviroglia both of the libers and cells. The latter are encroaching on the pyramidal cells. The glia cells I'ig. 24 (Case 1 ). — Sectien I'f cirvical region of spinal cord stained with cresylecht- violct sliowing sdihc antcrinr h.irn cells containing yellow pigment. This pigment is diffuse, slightly granular, and occupies the central portion of the cell body, the proto- plasmic substance being pushed to the extreme periphery. The two cells in the lower left hand corner of the field are practically nothing but a mass of pigment. (X 100.) are of two kinds: (1) a small and apparently homogeneous cell, and (2) a large cell with a granular nucleus which in many ways resembles a small lymphocyte. In sev- eral instances these cells, both large and small, are seen to be incorporated in the body of the pyramidal cells, and in one instance one of these larger cells is seen to be in- corporated within the nucleus of the nerve cell. The nerve cells, with but few excep- tions, show marked degenerative changes. They are shrunken, irregular in outline, and the protoplasm is not uniform in structure. The nuclei show chromatolysis and their outline is hazy. Their position varies, being either to one side or at the end of the cell. Some of the cells instead of being shrunken are tremendously swollen. In some cases, the nerve cell seems to have disappeared entirely or fallen out, tl# peri- cellular spaces being occupied by glia cells. The blood vessels also show a severe reaction. The perivascular spaces are dis- tended. The capillaries show a tremendous increase. One sees them in all stages of Page S16 LOUIS A. LURIE development, from the small, budding, rod-like projection to the thin-walled vessel with an almost imperceptible lumen. .'Ml tlicse pathologic changes gradually decrease in intensity as we approach the subcortical area. In the latter structure, there are many clear areas in which no nerve libers are seen. These areas are irregular in size and shape. In the larger ones, glia fibers have replaced the nerve fibers, giving the area a hyaline-like appearance. This is brought out very distinctly with the eosinmethylene blue stain. Right Peduncle: There is a uniform distention of the perivascular spaces, many of which are contiguous to foci of degeneration. Some of htese areas are cribriform or sievelikc in appearance. The pyramidal cells show evidence of involvement. Some are completely disintegrated, some have lost their nuclei and are highly granular, and others are pigmented. Satellitosis is marked. Pons: Small, clear, fairly regular areas corresponding, in all probability, to the miliary foci of Preobrajensky that were seen in the Weigert Section, are present in the raphe. The nerve cells do not show as great an involvement as those in the pre- ceding sections. Only a comparative few are entirely disintegrated and none show pigmentation. The perivascular spaces are distended. There are also patches of neuroglia overgrowth. Medulla: The nerve cells in the different collections of gray matter show uni- form degeneration of varying intensity. The pcricrlhilar spaces are enlarged. Pig- mentation occurs frequently. Some of the blond mss.K show a thickening of the intima and a small number are surrounded by small .irras ni degeneration. Cord: (Ccrru-ul r,;,i. ni) -Thvrr \< :i sharply dclined sclerotic area In llie pos- terior column wliirli is iilnitical Willi llial seen in the Weigert Sccln.n. Tins area is composed cliiell\" nf massnc \va\ >■ luindlrs ..f lu-uroglia fibers with which are inter- mingled an iiccasi.iiial undegeneralcd nr .inlx [lartially degenerated iur\ c (ibril. The nerve cells in the posterior horn appear shrunken in size and the nuclei do not stain well. The anterior horn cells show some pigmentation. This is especially of which are contiguous to foci of degeneration. Some of these areas are cribriform true of those in the lumbar region. The character and location of this pigment arc different from tli.it of the pigment normally present in the cells of people fifty years or older. In this case, the pigment is granular, and diffusely and evenly distributed ever the central portion of the cell. DISCUSSTOX A brief resume, contrasting the clinical with the ]xilhologic findings reveals a fairly uniform and definite relationship. In Case 1, we can assume from the history that the condition had probably existed for about three years although a blood examination was made only five days before death. On the clinical side we find a typical blood picture of pernicious anemia; absence of all the superficial reflexes with the exception of the left inguinal reflex ; absence of both patellar reflexes and sensory disturbances in the form of numbness of the feet. Mentally, the patient had visual hallucination.s, paranoid ideas and mild delusions of persecution. The necrop.sy report showed the characteristic changes on the part of the heart and stomach. Contrasted to this clinical picture there are definite pathologic findings. In the motor area we find characteristic vascular changes, pyramidal cell changes, satellitosis, vacuolization and the presence of the Lichtheim foci of degeneration. In the pons we have in addition to the above changes the miliary foci of Preobrajensky. In the spinal cord, the posterior column is practically entirely destroyed, especially in the cervical region. Neural and vascular changes are also present. Pigmentalion of the cells is pronounced and the neuroglia changes marked. In Case 2 there is a definite bloml ijiclure of pernicious anemia. From the history we can safely infer that the condition had existed for many years. Page .»? RANSOM OFF MEMORIAL VOLUME Clinically, there are neurlogical disturbances in the form of hyperesthesia of the lower extremities and an unsteady gait and mental symptoms simi- lar to Case 1, namely: visual hallucinations, delusions of persecution, and paranoid ideas. The necropsy examination revealed a pale, glassy atrophic stomach and a heart with tiger-lily striations. Histologically, the cortex showed areas of degeneration with vacuole formation, vascular changes, pyramidal cell changes, satellitosis and a marked increase in the neurogliar elements. The pathology of the pons was practically the same as that of the cortex, but again with the addition of the miliary foci of Proebrajensky. The spinal cord presented practically the same pathologic picture as the first case. In Case 3 the clinical picture is somewhat different. In the first place the patient was very young, being about nine years old at the time of his death ; in the second place he was a decided epileptic, and in the third place the onset of the pernicious anemia was acute. Hence, clinically, we have comparatively few findings. There were no neurological changes, but men- tally he showed delusions of persecution and paranoid ideas. During the height of the fatal attack, he showed a marked psychosis. On necropsy, there were slight changes in the stomach, resembling beginning minute ulcer- ations. The heart was negative. The brain showed a gain in weight, accord- ing to Tigges' formula, of 264 gm. However, Tigges' formula is not strictly applicable to children. Pathologically, in the cortex, the changes were similar to those in the first case except that they were less marked. No neurogliar changes were seen, which was to be expected, considering the short duration of the disease. On the whole, the changes in this case wen- the least marked. Here again, however, the miliary foci of Preobrajensky were found in the pons. In Case 4 the process evidently had gone on for several years. The blood picture was typical. There were marked neurological disturbances, all the superficial reflexes and both knee jerks being absent. There was also a distinct weakness of the legs. Mentally, there were paranoid ideas and delu- sions of persecution and other vague unsystematized delusions. No definite hallucinations were elicited. On necropsy the heart showed milk spots, white mottling, and minute hemorrhages. The mucous membrane of the stomach was shiny. The histopathologic changes were similar to those in Case 2. No Lichtheim focus was seen in the cortex. There was a marked increase in the neurogliar elements. Neuronophagic actions of the cells was marked. The pons showed the milary foci of Preobrajensky, the Lichtheim foci, vascular changes and slight nerve cell changes. In the spinal cord, the columns of Burdach showed the greatest involvement. The nerve cell changes were slight. Pigmentation was present. Also vascular changes. There was a considerable increase in the neuroglia. Page S18 LOUIS A. LURIE The following tables show these results in tabular form : TABLE 1.— SuMMAKY on Clinical Findings in the Cases Reported I. Duration: (a) From symptomatic stand- Case 1 Normal All absent ex- cept left in- Ruinal Numbness of f.et i Irfmon yellow Lemon yellow Yel. Pink Raspberry red EnlarRed white stria- 165 Rrams 1.800 Rrams Thick walls: glossy: no LossToS Minut'e^pecks of translu- cency in pos- terior columns Case 2 M,_rs N^o^sfe Hyperesthesia of lower ex- steady Rait + -1- -f Lemon yellow Not Riven TiRer lily enlarRement 185 Rrams 1.560 Rrams Pale. Rlossy. atrophic Loss 81 NoTsuled Case 3 ^cul^ Normal Normal Normal None None None -4- Yellowish '^No'r-Ri^^'n" Normal 160 Rrams 1.240 Rrams Ulcerations? Cain 264 China"w1ute softenine in posterior columns Case 4 (b) lyaboratory standpoint.. Several 3. NeuroloRic Findinss: (a) Pupils + (b) Superlicial reflexes Normal Absent (d) Abnormal reflexes (e) Sensory disturbances... 4. Mental FindiiiKs: (a) Hallucinations (visual). (b) Delusions of persecution. Absent None Weakness of leRs Doubtful -1- 5. Necropsy FindiuRs: (a) Skin (c) Marrow: (a) Sternum.. (b) Femur.... (d) Heart Pale yellow Richly red No enlarRe- ment. milk spots, white mottlinR: hem- orrhaRes 13.5 X 10 X (e) Stomach 23 xl6x7 cm. Mucous mem- brane shiny (i) Cord Not Riven Not stated TABLE 2. — SuMMAuv or Histologic Findings in the Sekies of Cases Reported From the above tables, it is evident that the neuropathology of the brain in pernicious anemia is larger and more fruitful than that of the cord. It is true, of course, that all these cases showed very definite mental symptoms and hence one would naturally expect to find cortical changes. However, in the case of J. H. (Case 3). who had a definite psychosis with no neurolog- RAX so J I OFF MEMORIAL VOLUME ical disturbances, tlie cord changes were by far more marked and bad pro- gressed much farther than the cortical changes. From this one might argue that in pernicious anemia, the first degenerative changes occur in the cord : then the process gradually extends and involves the brain. In the third case, there was also very little involvement of the neuroglia. This, as well as all the other points in which this case differed from the others, can be readily explained on the ground that this case had an acute onset and ran a very rapid course. The significance of the presence of the miliary foci of Preobrajensky in every section of the pons is open to speculation. Are these lesions spe- cific for pernicious anemia or is their uniform presence in the pons merely a coincidence? Obviously, one should not generalize from the findings of only four cases. However, to look on the regularity of their presence at merely a coincidence seems to me to be unjustifiable. At any rate, it is a point worthy of note and of further investigation. COXCI.USIOXS 1. There appears to be a fairly definite and constant relationship be- tween the clinical symptoms and the pathologic changes. 2. The psychoses can be classified with the symptomatic psychoses of a toxic-organic nature. The whole delusional formation is vague, unsystema- tized and loosely connected.* 3. The brain changes are even more marked than the cord changes pro- vided the disease has existed for a considerable length of time. This, in my opinion, is due to the fact that in addition to the toxic action of the poi- son on the pyramidal cells, metabolic changes also occur in the nerve cells as a direct result of the long standing anemia. 4. The blood vessels, pyramidal cells and the medullary fiber show simi- lar degenerative changes at different levels of the central nervous system. 5. The foci of degeneration bear a definite and distinct relationship to the blood vessels. 6. In every case, the miliary foci of F'reobrajensky were found in the pons. 7. Some of the nerve cells in every case with the exception of the third case, which was of very short duration, show dift'use pigmentation. 8. In speaking of the neuropathology of pernicious anemia, it is not sufficient merely to describe the lesions found in the spinal cord. The brain changes are too numerous and definite to be omitted. The neuropathology of pernicious anemia should include the entire central nervous system. I wish to express my thanks to Dr. Elmer E. Southard not only for placing the clinical material at my disposal, but also for his many helpful suggestions m carrying out this study. 1 also wish to thank Dr. M. M. Canavan for her kindly interest and capable supervision. These have been of inestimable value to ine in the preparation of this paper. My thanks are also due to Miss E. R. Scott for her care in the prepara- tion of the sections and to Mr. H. VV. Taylor for his care in the preparation of the photographs. * It is quitt! possible that fnrtlier investigation will prove that these psychoses are due to an encephalitis, and that therefore they belong in the ^roup uf encephalopsychoses rather than in the \ LOUIS A. LURIE BIBLIOGRAPHY Barker, L. F. : Monographic Medicine, \"oI. 3. Barker, L. F., and Sprunt, T. P.: The Treatment of Some Cases of So-Called Pernicious Anemia, J. A. M. A. 69:1919 (Dec. 8), 1917. Barrett, A. M.: Mental Disorders and Cerebral I^esions Associated with Pernicious Anemia. Am. J. Insan. 69:1063, 1913. Barrett, A. M.: Mental Disorders Associated with Pernicious Anemia. Fifth Biennial Report. State Psychopathic Hosp., Univ. of Mich., biennial period ending June 30. 1916. Berger and Tsuchiya: Arch. f. klin. Med. 94:252, 1908. Berthelot and Bertrand: Compt. rend. Acad. d. sc. 154:1463, 1912. Billings, F.: Progr. Med., June, 1900. Billings, F.: The Changes in the Spinal Cord and Medulla in Pernicious Anemia, Boston M. & S. J. 147:225 and 257, 1912. Bonhoffer, K. : Ueber psychische Storungen bei anamischen Processen. Berl. klin. Wchnschr. 48:2357, 1911. Brown, M. A.; Langdon, F. W.. and Wolfstein, D. I.: Combined Sclerosis of the Uchtheim- Putnam-Dana Type, Accompanying Pernicious Anemia, J. A. M. A. 36:552 (Mar. 2), 1901. Camac, C. N., and Milne, L. S.: The Spinal Cord Lesions in Two Cases of Pernicious (Addi- sonian) Anemia, Am. J. M. Sc, 190:563. 1910. Camp, C. D. : Pernicious Anemia Causing Spinal Cord Changes and a Mental State Resembling Paresis, Med. Rec. 81:156. 1912. Christian, H. A.: Renal Function in Pernicious .\nemia as Determined by Dietary Renal Tests. Arch. Int. Med. 18:429-444 (Oct.) 1916. Clark, J. M.: On the Spinal Cord Degenerations in .\nemia. Brain. 28:441. 1904. Dana. C. L. : Subacute Combined Sclerosis of the Spinal Cord and Its Relation to Anemia and To.xemia, T. Nerv. & Ment. Dis., 26:1, 1899. Coebel. W.: Ruckenmarksverauderungen bei pernicidse Anamie, Mitt. a. d. Hamb. Stalts- krankenanst. 2:1. 1898. Cordon, A.: Histolocical Changes of the Spinal Cord in Pernicious .\nemia .\proiios a Case Willi Diffused Degeneration, New York M. J. 90:8. 1909. r.rawitz, E.: Berl. klin. Wchnschr. pp. 704 and 730, 1898. Hunter, W. : Pernicious Anemia, Its Pathology. Septic Origin, Symptoms. Diagnosis and Treatment, London, 1901. Kahn. M., and Barskv, T.: Studies in the Chemistry of Pernicious Anemia, .\rch. Int. Med. 23:334 (March). 1919. Langdon, F. W.: Nervous and Mental Manifestations of Pre-Pernicious Anemia. T. A. M. A. 45:11,35 (Xov. 25). 1905. Lichtlieini: Zur Kenntnis der pernici6sen Anamie, Verhandl. d. Cong. f. inn. Med. 6:84, 1887. Marcus, IL: Psychose bei pernicioser anamie, Neurol. Centralbl. 22:453, 1903. McCrae, T.: Pernicious Anemia: The Statistics of a Series of Forty Cases, J. A. M. A. 28: I -IS (June 18), 1902. Minnich. W. : Zur Kenntniss der im \'erlauf der perniciosen .\namie beobachteten spinal Fr- krankungen, Ztschr. f. klin. Med. 21:25 and 264, 1893; ibid. 22:60. 1893. Moffit, H. C: The Function of the Spleen with Particular Reference to Haemolyses and the Hacmolytic Anemias, Bost. M. & S. J. 171:1639, 1914. Moffit, H. C: Studies in Pernicious Anemia, Am. J. M. Sc. 148:289. 1914. Nonne, M.: Weitere Beitrage Zur Kenntniss der im Verlaufe letaler Anamien beobachteten Spinalerkrankungen, Deutsch. Ztschr. f. Nervenh. 6:313, 1894-1895. Nothnagel's Encyclopedia of Practical Medicine, Am. Ed., 1909. Diseases of the Blood. Osier, William, and McCrae, Thomas: Modern Medicine, 1915. Patek, A. J.: Family Pernicious Anemia. J. A. M. A. 56:1315 (May 6). 1911. Pearce. R. M.; Krumbhaar, E. B., and Frazier, C. H.: The Spleen and Anemia, 1918, T. B. l.ippincott Co., Philadelphia. Pfeiffer. I. A.: Neuropatholocical Findings in Case of Pernicious Anemia with Psychic Impli- cation, J. Nerv. & Ment. Dis. 42:75, 1915. Preobrajensky, P. A.: Die Verandrungen im Nervensystem in einem Fille von Anamia Per- niciosa Acuta, Neurol. Centralbl., 1902, p. 727. Putnam, T. J., and Taylor, E. W. : Diffused Degeneration of the Spinal Cord, I. Nerv. it Ment. Dis. 28:1, 1901. Richter, E.: Ueber Spinal affektion bei letaler Anemia, Berl. klin. Wchnschr. 49:1976, 1912. .\. W. : Disturbances of the Central Nervous System, accompanying Pernicious Anemia. ungen in der Ilirnrinde bei schwerer .\namie. Berl. klin. wchnschr. 48:2357. 1911. Shaijiro: Ilerlung der pernicioser Anaemic durch abtreibung von Bothriocephalus latus. Ztschr. f. klin. Med. 13:1888. Strumpell, A.: A Textbook of Medicine, Vol. 2, D. Appleton & Co., New York, 1912, p. 58. Wiltschur: Zur Pathogenese der progressiven perniciosen Anamie. Deutsch. med. Wchnschr.. 1893. Woltman. II. W. : Brain Changes Associated with Pernicious Anemia, Arch. Int. Med. 21: 791 (June), 1918. Woltman, II. W. : The Nervous System in Pernicious Anemia: .\n .\nalvsis of One Ilundied and Fifty Cases, Am. J. M. Sci. 157:400, 1919. THE TUBERCULOSIS PROBLEM IN CINCINNATI.* B. F. Lyle, M.D., Cincinnati. PART I. \\'hile the science of eugenics is engaging popular attention and the re- sults of the activities of the spirochetse pallida and the corpuscles of Neisser are being disclosed to the public, the importance of the universal plague, tuberculosis, can not be obscured. The fact that the mortality from this disease in Cincinnati is large, and its relative frequency sufficiently marked to cause comment in other quarters, has been recognized by the profession and the public in general, although in no other place have there been more energetic, persevering and thorough efforts made to carry out those meas- ures which have been regarded as efficacious in stamping out the contagion and in caring for its victims. The fact that these eiiforts have had little or no effect in accomplishing the desired end makes it necessary for us to ascer- tain the recent discoveries in the field of tuberculosis in order that we may be able to work more intelligentlj' and hopefully. In the consideration of the subject it is important to know when and how infection occurs; if an individual once infected becomes immune to reinfection ; what influence early infection has upon the subsequent course of the disease. Fortunately the clinical manifestations of the disease do not give an adequate idea of the extent of the infection. In this paper an attempt will be made to show that tuberculosis is almost universally disseminated in civilized countries and infection occurs early in life; that the characteristics of the prevailing lesions and consequent variability and rapidity of progress depend upon heredity and the degree of communal infection; that the mor- tality from the disease is largely influenced by heredity, sanitation and climatic conditions; that our methods of prevention are faulty in conception and lacking in results ; that while there is a possible means of prevention, it is perhaps impracticable, makiiig it necessary for the community to wait for and depend upon inherited and acquired powers of resistance and im- proved sanitary conditions for general relief. As research work in this city and country is not sufficient to enable us to interpret local conditions, I have not hesitated to appropriate any ma- terial that will assist in the presentation of the subject and have drawn largely from the papers of Prof. Roemer in the "Beitrage zur Klinik der Tuberculose." One of the most startling discoveries of recent years is the proof that tuberculosis, like all other contagious diseases, is one of childhood and much of the exemption from its fatal consequences later in life is due to the establishment of a more or less complete immunity coupled with the pro- nounced natural resisting and recuperative power that is noticeable in child- F. LYLE hood and continues during the period of growth. The proof that tubercu- losis is almost universally disseminated and that infection occurs early in life is shown by the post-mortem findings and tuberculin tests made in many lands. As autopsy findings coupled with cultural investigations furnish in- controvertable proofs, it will be well to consider them first and also take their results as a basis to estimate the value of the less positive tuberculin tests. The most recent and authoritative are those made by Rothe, under the auspices of the Robert Koch Fund for the Conquest of Tuberculosis at the Institute for Infectious Diseases in Berlin. Out of one hundred non-selected cases dying consecutively of various acute contagious diseases, the majority of the children being under two years of age and none over five, it was found that 21 per cent, were tuber- culous; the findings were confirmed by the inoculation of guinea pigs. Gafifky, in a previous investigation in which three hundred children were examined, found tuberculosis present in fifty-seven. The work of these in- vestigators shows that about 20 per cent, of the children under five years of age, dying from various acute diseases in P.erlin, had tuberculosis of the bronchial or mesenteric glands. As the death rate from tuberculosis in Berlin is less than that of Cincin- nati (Berlin, 20.4 per 10,000; Cincinnati, 23.3), we are justified in conclud- ing that our children are infected to an ecjual degree. Hutinel, in 1895-6, in 220 autopsies of children between one and two years of age, found tuberculosis present in ii per cent. Kuss, in 1895-6, obtained the following results : Nothing to three months of age, 1.16 per cent, tuberculous; three to twelve months of age, 13 per cent, tuberculous ; two to four years of age, 50 per cent, tuberculous. Landouzy has found that among children dying before the second year : One in seven and one-half die of tuberculosis; one in si.x die of tuberculosis between birth and one year ; one in four die of tuberculosis between one and two years of age; one in three die of tuberculosis between two and five years of age. While these figures are obtained from hospital material in which tuber- culosis is very prevalent, they are significant and show that the fatality from the disease increases until the third year. Bollinger and Mueller, in 500 autopsies made in the years 1881-8, ob- tained the following results : Nothing to one year, 12.25 per cent, tuber- culous ; one to two years, 28.5 per cent, tuberculous ; two to three years, 36.9 per cent, tuberculous; four to five years, 61.9 per cent, tuberculous; six to ten years, 40 to 50 per cent, tuberculous ; ten to eleven years, 85 per cent, tuberculous. Recently Benjamin and Sluka have reported the following: Nothing to three months, 6 per cent, tuberculous ; three to six months, 17 per cent, tuber- culous; six to twelve months, 22 per cent, tuberculous; one to two years, 42 per cent, tuberculous. Comby, at the Congress in Washington, reported 1,447 autopsies, in 536 Page S23 RAXSOHOFF MEMO RIAL VOLUME of which tuberculosis was found. His figures are as follows : Four tuber- culous in 316 autopsies of children nothing to two months of age, 2 per cent. ; 39 tuberculous in 217 autopsies of children three to six months of age, 18 per cent.; 69 tuberculous in 254 autopsies of children six to twelve months of age. 27 per cent.; 141 tuberculous in 327 autopsies of children one to two years of age, 43 per cent. Hamberger obtained 9 per cent, of positive results in children under two years of age : Ranza found 14 per cent., and Paisseau and Tixier, in the Paris clinic, obtained the following: From birth to three months. 164 cases. 12 positive. 7.7 per cent.; three months to two years, 666 cases, 141 positive. 21 per cent. The latter have found that the results of the test in very young childrea are not reliable. They obtained six positive reactions from ten tuberculous children under three months of age. They find the results of their test cor- respond closely to the post-mortem findings of Kuss. Cohn" has shown the reaction to be much more frequent in children living in a tuberculous environment. By means of the Pirquet test in 273 children of tuberculous parents he obtained the following: Two to three years old. 66 per cent, of positive reactions; four to five years old, 66 per cent, of positive reactions ; six to seven years old, 77.5 per cent, of positive reactions ; eight to nine years old, 77 per cent, of positive reactions ; ten to eleven years old, 80.5 per cent, of positive reactions; twelve to thirteen years old, 89.9 per cent, of positive reactions; fourteen years old. 100 ]ier cent, of positive reactions. Pollok found 97.6 per cent, of the children in a tuberculous environment reacted, and even 96 per cent, of those two years of age were positive. These results strengthen the views of many authors that the opportunities for tuberculosis infection are as prevalent in the homes of the rich as in the rooms of the poor ; when the babies live in proximity to a phthisical mother, a father with chronic bronchitis, or a grandparent with emphysematous asthma, the conditions resemble those employed for the experimental inocu- lation of tuberculosis. Calmette has found that the infants thus exposed to repeated and severe infections give the following percentage of reactions: 9 per cent, between birth and the first year; 22 per cent, between one and two years; 53 per cent, between two and five years ; 81 per cent, between five and fifteen years ; 87 per cent, after the fifteenth year. In Kasanlik. during the past five years, ninety-seven males have died of tuberculosis; of these, 25.7 per cent, were under fifteen years of age and 74.3 per cent, over ; of the latter, 22.2 per cent, were married ; 62 per cent. of these had children, and their influence upon them may be given as fol- lows: 9.9 per cent, died before the end of the first year; 19.9 per cent, died between the first and second years; 30.7 per cent, died between the second and third years; 39.6 per cent, were living after the third year. Pat/c 32', B. F. LYLE Children of tuberculous mothers : Of the married women, 33.2 per cent, had been pregnant. The children can be classified as follows: 16.2 per cent, died between birth and the first year; 32.4 per cent, died between the first and second year; 16.2 |3er cent, died between the second and third year; 34.8 per cent, lived after the third year. When the father and mother were tuberculous, 30 per cent, of the chil- dren died of various diseases, mostly pneumonia; 60 per cent, died of tuber- culosis between birth and the third year; 10 per cent, lived after the third year. Siiiiiiiiary. — \\ hen the father is tuberculous, 39.6 per cent, live after the tliird year ; when the mother is tuberculous, 34.8 per cent, live after the third year; when both are tuberculosis, 10 per cent, live after the third year. These figures are sufficient to show the prevalence of tuberculosis early in life and the reliabilitv of the tuberculin tests. ;^ .g:_i^_- ..-....^^ _ 7^ -/|£|.^|'/|r|<^|;'|/'|i!! \^cr\//.\-fz.\/j\^'/-\fS-^ iiA-w/^^:, n ^ k .n k u 1 1 I 1 jtained by Calmette in Lille by the tuberculin test. (Beitrage Klinik der Tubcrkulose. ) We are now ready to estimate the dissemination of tuberculosis in civilized countries. Herford, from investigations made in the public schools of Altoona, Pa., has shown by the tuberculin test a minimum of 55 per cent, and a maximum of 78 per cent, of positive reactions. The children were not from the poorer classes, but from families in moderate circumstances. The higher figures were naturally obtained in those children who were in contact with tuberculous relatives. He arrives at the conclusion that the majority of children are infected before they enter school ; 2,598 children were tested with 20 per cent, tuberculin. In Bucharest, Nicolaesco and Nestor tested 2,000 children by the con- junctival method; between 65 and 66 per cent, were positive. Page 32S RANSOHOFF MEMORIAL VOLUME Calmette got like results from the Pirquet test in Lille in children of the working classes. They show from birth to one year, 8 per cent, positive ; one to two years, 28 per cent. ; two to five years, 65 per cent. ; after the sixth year, 92 per cent. These figures, from Altoona, Bucharest and Lille, are like those obtained from Vienna, Prague, Danzig, Paris, Dusseldorf , Berlin and Muenchen, and indicate liow universal is the saturation of children with tuberculosis in cities. Scheltenia found a somewhat lower proportion in the tuberculin tests of 520 children in the Groninger policlinic. He thinks this is due to the better character of the dwellings. In this work there has been a noticeable void because of a lack of investi- gations made in the country. Formerly we had only the careful investi- gations of Hillenberg, who. apparently, did not adopt the best method. z Von- Kinds™ reagiertea in -/N. UIH ^U IH/ k |*l*l^.|''^l^^ in ^ f, ■ I 1 ■ II II 1 1 1 1 1 1 II II 1 II i, 1. rn B 1 y n ■ 1 ■T n y u n M H m ■niii II II II II II II 1 1 M I! T.ABLE II. — Results obtained by Scheltema from the tuberculin test in Groningen. (Beitrage Klinik der Tuberculosa.) Jakop recently attempted to determine the extent of tuberculosis in the country surrounding Hanover. He gave the Pirquet test to 2,744 children ; L927 were between six and fourteen years of age and 817 between six months and six years. The responses from those attending school was 45.9 per cent. In the first year of school it was 35.6 per cent.; in the last, 64.1- per cent. Jakop gives no rea.son for inferring that the infection occurred in school and has concluded it was contracted at home before attendance at school. These figures also prove that tuberculosis is but little less prevalent among the country folk than among the children in large cities. The observations of Jakop are conspicuous in showing that when tuber- culosis was present in a house the children nearly always reacted; again, B. F. LYLE there were children who reacted for whom he could find no source of infec- tion. In cottages where there had been no one sick with tuberculosis for years 30 to 40 per cent, of the children recated. This is a proof of the re- markable diffusion of the yet unrecognized occasion for infection. Hillen- berg, in more recent investigations, obtained like results. He worked in a region where tuberculosis was not very prevalent ; the mortality from tuber- culosis being but 9 per 10,000. According to the statement of Koch this is the lowest in Germany. Hillenberg, in six country areas with an almost exclusive farming population and satisfactory dwellings, prosperous inmates and good sanitary arrangements; for cleanliness being also fairly good; a region where for ten years there had not been a death from tuberculosis discovered ; yet found 25 per cent, of the school children reacted to tuber- culin. A source of infection from coughing consumptives was excluded and likewise infection from cattle. As a result Hillenberg came to the conclu- % ^ 4L^^^ ^^^^.wi-^,..^ -^V l.^lvkk \?V\^VA^/VA^V-Vr. re it n yc St a? ■ 1 1 1 ■ ■ 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Table III.— Results obtained by Hilk-nl KliniU de rg in rural districts in Germany. Tuherkulose.) (Beitragt sion that here, as in similar instances, the tubercle bacilli in nature must have a wider scope than is usually recognized. "From a practical epidemiological standpoint one can hardly speak of anything more than an ubiquitous extension." Roemer believes it possible that those infected with latent tuberculosis may be able to spread the disease in a manner that is incomprehensible to us at the present time. This, of course, is a pure hypothesis based upon the results of veterinary practice and his own observations. It can at times be shown that the introduction of a tuberculous cow into a previously tubercu- losis-free stable leads to a gradual involvement of the entire herd to the extent that suddenly nearly all react; although this need not indicate that Page HI RANSOM OFF MEMORIAL VOLUME the imported beast is tuberculous in a clinical sense if the employment of other means of proving the presence of tubercle bacilli are negative. Hillenberg further investigated by examining the remainder of the people in these communities and occasionally, though rarely, found a case of tuber- culosis by means of the pirquet test. He found conditions to be as seen in the following diagram. At the conclusion of childhood he shows that 36.4 per cent, of the children were infected. The results in the several regions varied from 10 to 61.7 per cent. These figures are lower than those ob- tained in the large cities. It may be observed that Hillenberg carried on his investigations by the cutaneous method. Roemer believes that a more sensitive method would have shown a larger number of positive findings. Hamberger and Monti, when examining children between the ages of eleven to fourteen, with the cutaneous method, got 52 per cent, of positive reactions, but by the united cutaneous and puncture method 95 per cent. ■ X rMtioi mot tn. uw-ms -ah : un T>3 luTio or tkk LAinK.- lo .K I\'. — Showing comparati mortality from tuberculosis in Li periods. at various In Nothmann's investigations positive results were increased in 263 cases from 47.1 per cent, by, the cutaneous method to 77 per cent, by the stick- method. Even if the experiments of Hillenberg in the sparsely tuberculous areas indicate that the degree of involvement is not so great as in the large cities, we learn, on the other hand, the surprising fact that even in those places where tuberculosis is so rare opportunities for infection must be at the same time considerable. The enormous percentage of reactions that may be obtained in the chil- dren in a tuberculous environment is shown by the comparative tables ot Cohn. All these results strengthen the view that the opportunities for infection are so widespread that, at least in neighborhoods with a high morbidity from Page 328 B. F. LYLE tuberculosis, all children at the termination of childhood will be infected with tuberculosis. If it is a fact that this tuberculosis saturation is almost universal so early in life, it will be interesting to know why the period of greatest mortality is so far removed ; at least a score of years. That this is true is seen by our own records and those of other countries. Infection that is severe enough to be manifest almost invariably leads to n fatal ending if it occurs before the first year ; after this there is a period of fifteen years when the mortality from the disease is comparatively slight, although tuberculin tests prove the presence of tuberculosis in a latent state. This condition is not without advantage to the individuals infected, for we learn from animal experimentation, clinical, epidemiological and statis- tical findings that protection is thus aiTorded against a further tuberculous infection and an immunity is established of a greater or less degree, which, in the majority of cases, confers e.xemption for life from the serious conse- quences of the disease; and, in the majority of the others, the clinical course and pathologic lesions are so changed that we find the duration of the disease much longer and the anatomical appearances entirely different from those characteristic of acute tuberculosis. It may be of value for us to here consider more fully the advantages we thus enjoy from a danger from reinfection and the effects of more acute and fatal forms of the disease. A number of experiments have been made on animals, ranging from guinea pigs to monkeys, to learn the degree of resistance of the tuberculous to a further implantation of germs. The experiments made upon cattle some time ago by Marburger prove that an artificial infection with virulent tubercle bacilli confers immunity against a new infection. These facts have been recently confirmed and strengthened by Finzi in experiments upon eight calves suffering from spontaneous tuber- culosis. These experiments are important as they confirm the findings made upon artificially infected animals. The same results were obtained previously by Vallee and Calmette ana finally Roemer has shown there can be no doubt as far as animal experi- mentation can show that an existing infection, either natural or artificial, is a protection against further infection. He first inoculated guinea pigs, but, because of their great susceptibility, concluded his experiments with sheep. He finds, however, the immunity is only relative and a very heavy assault can cause the immune body to succumb, even if at a much slower rate than occurs in the non-immune animal. It is now proven by animal experimentation, and confirmed by a large series of statistics, that a strong infection in a partially immune organism leads to forms of tuberculosis that are entirely different from the results of a primary infection, and it is because of this that human tuberculosis can clinically and anatomically exhibit very dissimilar disease aspects ; the view is also permissible that through this strong immunity the organism can over- Page S.iO RANSOHOFF MEMORIAL VOLUME come a severe infection. Roenier believes it must be accepted that the effectual reinfection leading to phthisis does not originate outside, but must be already present in tuberulous foci ; in other words, it is a metastatic auto- inoculation. There are difficulties in explaining these conditions. A reinfection that may be interrupted in adults results in a child in a marked degree of involvement. Roemer, in co-operation with Joseph, has established that the immunity of tuberculous individuals against a new in- fection in many cases does not depend upon a destruction of the newly intro- duced bacilli; at least, in animals proven to be immune by reinfection, living bacilli could be shown at the place of inoculation. Again, the serum of highly immunized sheep was not able to destroy the tubercle bacilli in a single instance under favorable conditions. Roemer believes the immunity to be a labile one and resembles the form of immunity we see, for example, in the perophasmodium of cattle (Texas fever). Animals that have overcome the acute infection remain infected with the living virus but are immune to a new infection and can remain with- out danger in infected meadows. We must presume that tuberculosis immunity is specific in nature, although not marked as in the cases of more acute diseases: the intensity of immunity usually being in proportion to the sensibility of the individual to the contagion. The fact that tuberculosis is a disease usually contracted early in life makes the environment the chief predisposing factor. Investigations have shown that in 50 per cent, of the active cases of tuberculosis in children a parent had open tuberculosis. What had been regarded as predisposing factors in the causation of the disease we may now consider agencies, which, by reducing the inherent or acquired immunity, permit what would be a latent process to become active. If we were to attempt to individualize these pernicious agencies, although they are characterized by team work, half a dozen or more could be selected, any one of which is sufficiently important to be considered the principal and all must receive practical attention before the dawn of the non-tuberculosis era. Without attempting to cover the field we may mention poverty, alco- holism, the location and character of dwellings and shops, unsanitary occu- pations, particularly those of the "blind-alley" kind; child labor and long hours of labor. These are factors because of the chronic nature of tuberculosis. They are not predisposing causes, except in so far as they may be instrumental in increasing the sources of contagion. Ignorance and overcrowding are im- portant but not essential factors in all contagious diseases. It is interesting to notice the influences attributed to heredity at different times. At first it was regarded as the most important element in the origin of the disease; then it was maintained that a peculiar vulnerability of a specific character was transmitted from parent to child ; today it is regarded of importance because of the immunizing capabilites that are transmitted. The individual Page 330 B. F. LYLE is not supposed to be protected from the infection, but is shielded by a partial immunity manifested by a difference in the nature of the lesions induced; they being of a much more chronic type ; the life of the victim is thus fre- quently spared at a cost of physical vigor and frequently he is held as a hostage for the dissemination of the germs. That the influence of heredity is potent is attested by many recent investigations.' - We are therefore forced to the conclusion from a study of the relative mortality from the disease and the variety of its manifestations in various peoples and races that heredity must play an important part in determining the character of the lesions and the percentage of mortality. We find this is also true of the contagious exanthemata; the Chinese and Japanese being exempt from scarlet fever, while the natives of newly discovered islands die in great numbers when they are first infected with hitherto unknown con- tagious diseases. The Jewish people from a long familiarity with tuber- culosis enjoy a comparative immunity from its fatal consequences, although they evidently possess no exemption from manifest infection. jHr — r /lii— X-:! Table V. — Showing the relative proportion of the acute and chronic forms of tubercu- losis at various ages in civilized countries. (Eeitrage Khnik der Tuberkulose.) Rothe is of the opinion that the early infection results in the establish- ment of an immunity that protects the majority of persons from any further manifestations of the disease and in others leads to a marked prolongation of the evolution of the pathologic process. He believes that as in syphilis we find various phenomena making their appearance in a fairly orderly suc- cession, due to the gradual involvement of tissues that at first were invulner- able, so in tuljerculosis do we find a like condition. Thus, we can dififerentiate : First, a stage of generalization (glandular tuberculosis) having an origin directly from the infection; second, a stage of hematogenous dissemination, characterized by scrofula and bone and joint involvement; later, we have phthisis with its sequelae, involvement of the larynx and intestines and other organs. RANSOHOFF MEMORIAL VOLUME That exeiiiinioii from the more acute extensive tuberculous processes characteristic of the disease in the non-immune individual is due to the pro- tection secured early in life is shown by the clinical aspects of the disease in sparsely settled countries and among those races which have but recently been brought in contact with the disease. If the tuberculosis does not cause a rapid death it leads to increased re- sistance against tuberculous infection, thus preventing contagion from the outside later in life. The degree of immunity is not sufficient to destroy the bacilli present and the involvement of organs later must be the result of auto-infection. We have an analogy of this in malaria. Roemer ap|)roves of the conclusions of Hamberger, whose observations showed that after a reinfection of guinea pigs the place of inoculation re- mains for a long period reactionless ; but, however, when for any reason the immunity is lost, even after a series of months, the hitherto weakened tubercle bacilli gain the upper hand and cause an exacerbation of the tuber- culous processes. Numerous individuals, in spite of such reinfection, do not become phthisi- cal. There is also reason for maintaining that certain groups of individuals are also immune to tuberculosis. It is no doubt true that children who suf- fered from a relatively severe infection in childhood are more prone to posi- tive results later in life, due to metastatic auto-inoculation. In 1908-10. Freymuth examined the histories of 1,400 adults and 328 children ; as a result, he came to the important practical conclusion that it can not be acknowledged that there is any necessity for the separation of open and closed cases in a sanatorium. The most startling investigation in this line is the work of the Japanese, Kurashige, who. by means of a modified anti-formin process, found bacilli in the blood of 155 tuberculous patients in various stages; not only this, but in twenty of thirty-four investigations of clinically healthy adults (59 per cent.) he found tubercle bacilli in the blood. In four the findings were con- firmed by inoculations in guinea pigs. These results were confirmed by Luzuki and Takaki, who found tubercle bacilli in the blood of 509 out of 517 tuberculous patients and in twenty-eight out of fifty-four clinically healthy men. These twenty-eight gave a positive Pirquet and in none of those who did not react were the bacilli found in the blood. This shows the fallacy of the old belief that bacilli in the blood leads to miliary tuberculosis. It shows there is no correspondence in the results of the inoculation of normal animals and those who are already infected. Acs- Nagy, months before the demise of patients, found tubercle bacilli in the blood without miliary tuberculosis resulting. It has been maintained that the ])rogression of the bacilli in the various organs varies greatly, according as the implantation is introduced into a normal individual or into one with tuberculosis. This is shown by epidemiologic examinations. Page SiZ B. F. LYLE PART TI. In countries in which there is a comparatively shght amount of tubercu- losis in adults we more frequently see the more acute forms of tuberculosis characteristic of childhood. ■ In this connection the observations of Deyckes in Turkey, of Romer and Nine in Argentina, and of Westenhoefifer in Chili, are confirmatory. In autopsies made by the latter, in Santiago in 1908-9, he found the dissemination of tuberculosis to be much less than is seen in the post-mortems of European pathological institutions. Not more than half the amount was found and there was a remarkable difference seen in the forms of the disease. In forty-five who had died of pulmonary tuber- culosis only twenty-eight had the chronic form and even in these there was a failure of connective tissue formation and large cavities. The majority of the cases were of confluent caseous pneumonia, a form of tuberculosis we are accustomed to see in the children of Europe. Westerhoefifer says that at least one-third of the cases are of very acute forms. He ascribes this difference to the fact they have not had the early protection of a latent form acquired in childhood. ^ X y r-' -/- : ' / lL ~y /■ 40 f ^.'> \ / Pe 0^« U9C .0 \ 1 / " A 'r s^ ^ ^ ' Tahi.E VI. — .After Escherich. Showing the relative mortality and morbidity in children in Vienna in 1909. ( Wien. med. Woch.) In support of this the observations of Metschnikofif, Burnet and Tarasse- vitch, made in Russia, are important. They found that the sons of Calmuck families, when sent to the more advanced schools of Astrakan, died at an astonishing rate from acute tuberculosis. Phthisis was relatively rare. Like observations were made by Metschnikofif and others in Austria which show that in the regiments sent from Bosnia and Herzegovina the soldiers died with greater relative frequency from tuberculosis, notwithstanding the fact that the disease is not very prevalent in their own provinces. These observations help us to solve a problem with which Koch was busy in his last years. It is known that in Germany and in other civilized coun- tries the death rate from tuberculosis has decreased since 1880, while in Norway, Ireland and Japan it has increased. The above epidemiological RAXSOHOFF MEMORIAL VOLUME experiments, taken with the tuberculosis immunity observations, offer the key to the still unsolved problem. "The less prevalent tuberculosis is among a people the greater is the toxicity of the disease." That is, increased mortality to morbidity. This indicates the presence of the more severe acute forms of the disease in a slightly contaminated population, either from rarity or failure of the milder chronic phthisi. As a result we may express the formula, "The more widely spread the tuberculous infection the less the relative mortality." The meaning of these two precepts is appreciable when we remember the facts tuberculosis im- munity represent ; that is, keep in mind that the tuberculous individual is ap- parently protected from outside new infections. The auto-infection from within, even if severe, shows there is a relative immunity in that not a gallop- ing consumption but a chronic phthisis ensues. By means of this resistance in those countries in which tuberculosis is the most extensive; in which tuberculous saturation has reached its highest tide, the mortality rate from tuberculosis had materially declined. The accompanying charts, showing the tuberculosis record of Hamburg for the last ninety years, proves this conclusively. Of course, we are apt to consider that the significant and remarkable changes in the mortality rates of an epidemic scourge depend upon artificial influences and it is humanly comprehensible that even medicine is willing to claim that the credit for these improvements is due to her own scientific acquisitions. No doubt, however, were the history of plagues better known and the variations in the intensity of infectious diseases better comprehended we would not agree too lightly to such claims. We are reminded here of the disappearance of the plague from Europe at the beginning of the eighteenth century, the reason for which is not clearly understood, and remember how often, still earlier, when the epidemic was absent for one to ten years, in every instance the methods employed were promptly credited as the cause. We are cognizant of the remarkable changes in the mortality rate of smallpox in very recent years. Finally, we may refer to the experiences of life insurance companies obtained in an experi- mental way. They do not reject individuals who are free from a history of hereditary tuberculosis and whose personal record is clear when they are living or have lived with a tuberculous partner. Little regard is paid, at least in Germany, to the danger of an adult living with a tuberculous mate, and one can not accuse the insurance coinpanies of being careless. In conformity with this is the record of so experienced a physician in tuberculosis as Petruschky. When mentioning the dangers that marriage brings to the tuberculous he touches upon the danger of infection through the tuberculous partner and states as laconically as impressively : "From re- ports not yet observed." In this connection we can state that before the dis- covery of the tuberculous germ many physicians did not believe in the con- Page Ui B. F. LVLE %,: ■: -: •: t : : o f .«< ill iiii 11; zjl - : : :=:|^^"- --■==:H! MTOlWW — t- ^t t- *- ^^S "^ — liii ;=zE^3^||3|i -=c^ It j= =t" -a*" ^ " - '>'>"i - = == = ^---"f-:=-' 5^^EEEEEE:EEEEi; i-^=-i=^^¥-i irnTH' i ' "" ^I^Si^^-r. 5 TIl!ijMi4:MT4::rt iin ! i"", 1 1 f i , — UU :^« ^- 1 ' ' " ' ! M 1 1 1 P TWl ^^SEEEpf! mSmm _k„ h'H-^^nTT^^Ui^^ry 1 rpi -1 — ' — hr ^"! r^"" '"• -4-l-^--H--H 1 !{:; =i=-EE4£d^II:^ je- — "" = g||_^_ = = = = =| Hiifc^^ - = = -Tit=E-rEEE|: = ^i-5 -= = --— -^ :;;; ,906 Table VII —Showing progressive decrease in mortality from tuberculosis in Hamburg during the past ninety years. (Beitragc Klinik der Tuberkulose.) RAXSOHOFF MEMORIAL VOLUME tagioiisness of tuberculosis because they saw many persons remain in close contact with consumptives without apparent injury. In striking contrast to this are the recently reported investigations of Jakob, made in a badly infected region in the neighborhood of Osnabruck. He mentions the danger that might arise through dwellings and makes the following observations: The wife of a healthy man died of consumption. Some time after he married again and this wife died from the same disease. The same occurred with the third and fourth wives. Jakob thinks this re- sulted from a house infected with tuberculosis. It is remarkable that the husband remained well in the house and Jakob states he has never seen the second husband of a healthy wife die of consumption whose first husband had died from the disease. Metschnikoff, Burnet and Tarassevitch, in the report of their work, men- tion a similar observation. One of the authors of the book lived for a year with his wife, who had a fatal form of consumption, without contracting the disease. Why is it that a house that is infected sufficiently to be fatal to the in- coming wives was not fatal to the husband? It may be remarked that Jakob indicates the marked prevalence of tuber- culosis in the people of this region, so that it is plausible that the man in every instance had married an infected woman in whom pregnacy, child- birth and the puerperal state had favored the progress of the disease. The objection that it was a peculiar coincidence that a man should marry a tuber- culous woman in every instance appears out of place. The consumptive \'enus of Botticelli was regarded for years as the ideal of a perfect female form; therefore, why should there not today be an individual who ignorantly and fatefully turns only to a consumptive type? Finally it must be men- tioned that Jakob, as a result of his careful research, is of the opinion that the infection during childhood, as a rule, potently influences the after-life of some persons. The fact thus proven by clinical, epidemiological and statistical investi- gations that adults enjoy an appreciable or even absolute protection against a new infection from without emphasizes the fact that when children they had a mild infection. What shall we say about the tuberculosis situation in Cincinnati ? What are the results of the measures that have been employed? What course shall be pursued in the future ? In the decade, 1901 to 1910, the death rate in the United States from tuberculosis declined from 196.9 for each 100,000 to 160.3, a decrease of over 18 per cent.; while the general death rate from all causes declined only half as mucli. at the rate of 9.7 per cent., or from 1655.0 to 1495.0 per 100,000. We are informed by Dr. Maurice Fisher that in Germany within the last five years the mortality from tuberculosis has ceased to fall. Page 3.% F. LYLE Prof. Walter F. Wilcox, of Cornell, consulting statistician of New York State, in his reports for the years 1909 and 1910, states that the campaign against tuberculosis has as yet made no change in the tuberculosis mortality nf New York State. A glance at the death statistics of our city shows that the mortality from tuberculosis bears a certain relation to the general death rate. In other words, any measure or condition that influences the death rate in the city has a proportionate effect upon that from tuberculosis. The rate among children seems to be greatly reduced. This seems somewhat remarkable when we bear in mind the results of the observatiohs of Landouzy and other Continental writers, although they correspond to the observations noted re- cently in Switzerland. It is very difticult for us to determine the mortality from tuberculosis among children previous to the beginning of this century, owing to the fact Tuberkulosesferblichkeil m dcr Sfadt Hamburg. Auf Je 1000 Lebvnde derselben AlUrskiasse Slarban im AUer von c-i-ij. - u-N-M-joJ. JO — »oJ 50— loj ub«noJahre ,,_ , / "^ J \ -.^ v I ^v ;5 J ~7 .... — ■-- -« •* ^ \ / ■' ^""x '- "^ N ^ 4^ ^^ ■'••■-^ ^ i/:"" ^ "-IHI :rv/;-""'^'- ^^- %\y S;..-rr^. 1872-1898. rrr. 1899 -1910. Tabi.k VIII. — Showing the influence on adult mortality of tuberculosis at various periods. (Beitrage Klinik der Tuberkulose. ) that our health office reports show that about the year 1880 hydrocephalus prevailed to a great extent and was classified as tuberculosis. Ten years later this uncertain term had given place to marasmus. Prof. P. G. Woolley, who kindly glanced over the statistics, advised the exclusion from the list of deaths from tuberculosis those which were at- tributed to these causes in children under one year of age. In the first period shown no records can be found of extra-pulmonary forms of tuberculosis. The same proportion as given in the following de- cade was used in order to obtain an approximate estimate of the total deaths from tuberculosis. In order to make the estimate as reliable as possible the records of the census years and the two years preceding and following were taken and RANSOHOfF MEMORIAL VOLUME the average employed. The great mutations seen make this necessary if we aim to secure reliable data. These statistics show that the general death rate in our city has been progressively reduced, no doubt due largely to the diminution of the mor- tality among children. The present tuberculosis death rate is higher than that of the previous Table Shozving Death Rates for Census Years and the Two Years Preceding and Following, with Averages. . of children To ,a> niimbei ol deaths from tulierciil •s - g ^ J g >• .- i. - -, "■• - 1868 4424 443 1869 3740 447 1870 3978 58' 1871 5291 580 1872 5116 616 Av. 4510 *576 534 *42 1878 4823 705 659 46 52 22 10 17 1879 5290 740 698 42 55 22 9 5 1880 5177 771 720 51 53 ]/ 17 8 1881 6110 997 9m 93 81 38 14 14 1882 6873 846 783 63 59 26 17 17 Av. 5653 812 753 59 60 25 13 12 1888 5994 903 746 157 75 20 21 18 1889 5922 878 731 147 60 28 12 16 1890 6441 913 7.S6 157 58 97 15 19 1891 6635 700 643 46 26 18 12 1892 6015 817 647 100 61 31 13 14 Av. 6201 842 704 138 60 -25 16 16 1898 5885 729 642 87 22 16 16 14 1899 6000 804 692 112 39 21 7 14 1900 5412 714 635 79 24 16 q 1901 6155 822 742 80 14 19 14 9 1902 5744 736 647 89 22 14 3 11 Av. 5839 761 672 89 24 17 10 11 1908 6449 952 860 92 21 13 10 13 1909 .5921 947 850 97 39 20 9 12 1910 6330 1025 912 113 35 19 12 12 1911 6225 986 876 110 13 10 13 1912 6453 968 856 112 33 18 10 12 Av. 6278 976 871 105 30 17 10 12 • Exlra-piilmonary forms not recorded and same proportion given as in foflowine decade. decade and the same that prevailed forty years ago, before Koch discovered the specific germ and fifteen years after \^inemin had established the con- tagious character of the disease. The diminution in the deaths from tuber- culosis has not kept pace with that of the general death rate. Dr. Schmid, director of the Swiss Health Office at Berne, states that tuberculosis has decreased in Switzerland since the middle of the eighties. This decrease is especially noticeable in the younger element of the popula- Paac 338 B. P. LYLE Table Shozi'iiitj Average Death Rates of Various Periods and Giviiicj the Ratio of Deaths from Tuberculosis to the General Death Rate and to Population 1870 216,239 4510 1880 255,139 5653 1890 296,908 6201 1900 325,902 5839 1910 364,463 6278 *576 534 *42 812 753 59 842 704 138 761 672 89 976 871 105 recorded aiul same proportion p .127 208.6 26.6 .144 221.9 31.8 .136 208.8 28.3 .13 179.1 23.3 .155 172.0 26.8 tion, while it has increased in those above sixty. The most remarkable de- crease has been in children in the first five years of life. Out of 10,000 there were 29.0 deaths in 1901 ; this fell to 18.4 in 1908. W'liile our records in Cincinnati are confusing on account of the pecu- iiarilics in nomenclature or divergent views as to the significance of clinical conditions, an examination will show an apparent diminution of the number of deaths among children. They prove this not only to be true of tuber- culosis, but of other diseases. In 1886 the deaths among children under five years of age constituted 42.86 per cent, of the entire mortality rate; the ratio for the city being 18.98 per 10,000. In 1911 the deaths in the early years of life had been reduced to 17.26 per cent, of the whole, the general mortal- ity rate being 17.23 per 10,000. This makes very pertinent the inquiry: Does not the favorable showing depend upon this enormous saving in the lives of children? A close study of these statistics will indicate that they are more significant than surface indications show. An investigation which I made in order to estimate the comparative death losses of various parts of the city showed the average loss per 10,000 to be 22.5; in the oldest portion of the city near the river it was 38.0; the average of the rest of the basin and the hillsides was 22.2; while on the hilltops the rate was only 12.5. We must now recall the fact that in 1870 Walnut Hills was the only large suburb. It had a comparatively small population which depended upon omnibu.ses for transjiortation. Ten years later the same conditions prevailed. Horse cars began to go to Walnut Hills about 1880. Before 1890 the boundaries of the city were extended and suburban areas with small death losses from tuberculosis were absorbed. The advent of the electric cars be- fore the next decennial and the inclusion within the city limits of large suburban areas slill further enlarged the are;is of the city favorable for residence purposes. Page ..'.!» RAXSOHOFF MEMORIAL J'OLUMF During the past ten years conditions favoring a choice of suburban homes liave improved: notwithstanding the dcatli rate from tuberculosis has in- creased. This is possible because sanitary measures, though indispensable and in- valuable, do not prevent infection. It will lie well to consider this aspect of the subject in order that our views on the prevention may be made more definite. It seems somewhat incomprehensible that at an almost legally established time at the conclusion of the body maturity a large reinfection or rather recrudescence of the disease should occur. It is not possible to give a complete satisfactory explanation of this, although it may not be particularly remarkable that at such a period of life with such pronounced evolutionary changes in the organism that many slum- bering germs in the body find conditions favorable for development. Hart believes that he has found the lacking scientific explanation, and suggests that important mechanical incongruities in the region of the upper thorax lead to the causation of pulmonary tuberculosis. That this view is not generally accepted is shown by the position of Reiche on the heredity of chest conditions predisposing to lung phthisis, and further on the importance of the habitus paralyticus and its extent in phthisical families. He thinks it will be necessary to know whether it is a cause or an effect before we can decide. Pottengers' observations are in striking contrast with the views of Hart and Freund as to the cause of changes in the upper thorax cavity so fre- quently found in consumptives. He believes them to be due to the tuber- culosis. Williams years ago established the fact that even in early tuber- culosis a hypertonicity of the muscles of the diaphragm caused a diminished movement upon the diseased side and was an early diagnostic sign. Pot- tenger holds that this hypertonicity involves all the muscles of respiration on the involved side, particularly those of the neck. This muscle spasm dis- turbs the movements of the upper part of the thorax causing a narrowing of the intercostal spaces and anchylosis of the costo-sternal and manubrio- sternal articulations. He also believes a careful observation of the appear- ances of the upper portions of the chest will convince one that the relations between the tuberculous lung involvement and these abnormalities is one of cause and effect. The doctrine of the importance of the paralytic thorax for the develop- ment of phthisis, on the one side, and the theory of the influence of early infection as a factor for the development of consumption in adults, on the other, are somewhat bridged over by these new views. Pollak, a pupil of Hamberger, brings proof that it is not always true, as has been maintained, that infection in the first year always causes death. He shows that a third of those infected go over into the second year without offering any prognostically bad symptoms. He believes that infected infants that do not die of the disease gradually acquire a typical tuberculous habitus. Page S'lO F. LYLE r- r-t-f- t^t^t^T^ <«)*«» 'o<^c>«^«> c^t'ooQoottOOOo-i Sterblichkeit an Lungen&chwind&ucht auf je 1000 (m) . - 1000 [w) " (Tuberculose an-i » . -1000 ^m) - I derer Org a ne » - - 1000 (w) inderStadl Hamburg 187£-I9ll. Table IX. — Showing the reduction in mortality is not due to growth of the city, but to the increase of inherent powers of the inhabitants. RAXSOHOFF MEMORIAL VOLUME He maintains that the later the infection occurs the less is the liability for clinical manifestations and believes they are seldom seen in children infected after the fourth year. Whether this is due to a previous light infection or is caused as a physiological result of increased resistance he does not state. At any rate, these observations teach we must recognize an immunity of the growing organism toward outside infection. They also make very improb- able the view that consumption in the adult is the result of exogenous infec- tion and support the contention that the infection of early years causes the tuberculous habitus, and therefore will be the cause of the later phthisis. Roemer accepts the views of Pottenger and Pollak, but still maintains that the physical habitus can arise independent of tuberculosis ; in his opinion he is supported by many observers. Roemer believes observations should be made to ascertain if men clinically considered non-tuberculous, but with typical paralytic chests, will remain negative to sensitive tuberculin tests (the stick method). Conditions may be defined as follows : If tuberculous infection does not cause rapid death it leads to increased resistance against a tuberculous infection. The resistance so caused is potent in preventing outside infection in later years. Particular conditions of a physical or jiatliologic kind due to the incor- poration in the body of the tubercle bacilli are such that the degree of im- munity is not sufficient to prevent a metastatic reinfection. Thus it occurs that a new focus develops with renewed manifestations of tuberculosis. Experience teaches us to view these as metastases caused by a relatively severe infection in childhood. A particularly disposed local condition for the origination of this second condition is perhaps in evidence. From epidemiological reasons Hillenberg opposes these views. In his in- vestigations on the spread of tuberculosis in a neighborhood with but slight saturation with tuberculosis he found a not insignificant number of children infected. He therefore concludes that the elders of these children in their youth must have been proportionately infected, and thinks it strange that in spite of this so few or none in later life became consumptives, although when children they were infected with latent tuberculosis. Roemer directly opposes this view and insists that the large majority of infections in children do not result in consumption in later life and are never noticeable except by the insensible protective influence against further in- fection ; he further insists that in those cases in which consumption appears later a particularly severe early infection occurs. In the territory investi- gated by Hillenberg he thinks there was no indication of serious early infec- tions, and the failure from consumption of those only lightly infected in childhood is not a contradiction of his views, but a support of their correct- ness. Ranke has recently devised a very interesting chart tliat shows ihe death Page m B. F. LYLE rate from the recognized forms of the tuberculosis of children and adults. The one being characterized by acute general tuberculosis, the other by chronic phthisis. These forms are seen in two curves. We believe the for- mula correct which states "that phthisis is an after-disease of generalized tuberculosis." The increase of mortality from the sixteenth year on can be caused theo- retically by increased facilities for infection; practically this in the highest degree impossible, for phthisis does not immediately follow an opportunity for infection, but very frequently appears to arise spontaneously after inner or outer general or local injuries. Ranke shows that the phthisis of adults is the result of the changes in- augurated by a previous infection. For further proof he indicates the rarity with which consumptives have the trachea, mouth, fingers, nose and eyes involved, notwithstanding daily opportunities for infection. He mentions (^,z% '^ia ■.::'u\'y< m I I = Itlinisch gesund und nicht tuberkulinroagierenJ. ED 5 klinisch gesund. aber tabeikulinreagierend. H s tuberkulosekrank. Tahle X. — Diagram sliowing the relative merit of protective measures taken before and after the birth of the child. again the rarity of hemostatic metastases in phthisis in comparison with their frequency in general tuberculosis, although it is proven that in phthisis the tubercle baccilli are frequently found in the circulation. Ranke proves further that when secondary infections occur they are of the type of .superinfections and due to a saturation of the blood with bacilli when the resistance is low. In the efforts to combat the spread of tuberculosis it must be attacked from a new viewpoint. It is shown by the practical consequences that in the fight against the tuberculosis we must either prevent the severer forms of infection, which are RAXSOHOFF MEMORIAL VOLUME ultimate cause of the varities of tuberculosis found in adult life, or we must prevent the ominous metastases in individuals infected in infancy. It is self- evident that only the assault of both positions can be efificacious. Because of the fact that tuberculosis is a result of infection early in life, Roemer is not an ardent advocate of the advocacy of a personal hygiene that endeavors to inaugurate an efifectual antagonism in adults. He believes this practice con- trary to natural processes as is shown by experiments in animals. In eliminating cattle tuberculosis no hygienic rules are efficient ; only methods that prevent infection show positive results. The complete inefficiency of the hygienic method can not be better illus- trated than by the facts established by the veterinary service in the Hessian district where, notwithstanding extensive efforts to prevent tuberculous satu- ration the loss in the majority of instances was very considerable, while the lamentably appearing dark stalls of the small farmer were almost tubercu- losis free. In the pampas region of Argentina the spread of tuberculosis among cattle was unopposed, although they were living under the most favorable conditions in the open air in a sunny climate, until the owners concluded to exclude English breed cattle. As long as there is a source of infection open-air conditions are useless, and when calves are fed infected milk, as is done in many parts of Europe, the attempt to make general hygienic measures efficient are useless. While isolation of consumptives is a relative isolation it is in line with the pre- vention of infection. The efforts to cure tuberculous children by means of open-air schools and nourishing food, by means of sanatoria and isolation homes, is a duty. Of all measures of prevention the protection of the child is the principal one. This does not exclude other methods. The effort must be made to prevent severe childhood infection. If it is known in what families tuberculosis is present a great advance will be made. This may be ascertained by the Pirquet method. If the children can then be protected a great problem will be solved. By following out this method Effler has already attempted to judge the efficacy of this plan. While his results are few they are remarkable. With sixteen children born and brought up in families in which before their birth proper methods were counseled there were at the time of the investigation eight well and not responsive to tuberculin; seven clinically well but reacting; one had pronounced tubercu- losis. This child was from parents with open tuberculosis, and. because of this, the measures of prevention could not be thorough. Of nineteen children in which measures of precaution were taken after birth in open tuberculous families, four were healthy and non-reacting; eight healthy, but reacting; five were tuberculous. These figures are small, but very suggestive, and indicate what is necessary. We know how to protect the children ; we possess means to control the disease ; we must now use them. B. F. LYLE It is first necessary to be convinced that the secret of the origin of con- sumption lies in early life, which then becomes the field for strenuous effort. The opportunity to establish the truth of these investigations lies in the field of the family physician. Upon him alone will rest the responsibility for results. In the accomplishment of this duty he will be supported when necessary by the strong and persuading influence of the health department and such other organizations as earnestly labor for the eradication of the tuberculosis scourge. DIZZINESS. M. F. McCarthy. ^\. D.. Cincinnati L'litil comparatively recently we lia\e not had at our command the means to study and classify the causes of dizziness. Until the last decade our understanding of the mechanism controlling balance, the disturbances of which could result in dizziness, was very hazy, being made of the uncorre- lated eflforts of laboratory workers whose deductions were made for the most part from animal experimentation. In 1825 Flourens made excisions of portions of the labyrinths of animals and noted that this caused movements of the eyes and definite disturbances of equilibrium. Purkinje at the same time made experimental studies in turning human beings and made observations on the resulting ny.stagmus and vertigo. In 1861 Meniere published his now famous case history of Labyrinthine Haemorrhage, verified by post-mortem examinations, and by his accurate observations established the syndrome known to be typical of the so-called ""Meniere's Disease." Ewald and Hoegyes, after years of pa- tient endeavor and research, were able to state some of the basic laws of labyrinthine physiolog)'. From the observations of these two men, together with the added experience of other investigators, Roliert Barany was able to draw the material for his magnificent work which has brought labyrin- thine studies out of what was entirely impractical state and into the prac- tice of the clinics. His most notable contribution was made in 1913 and since that time many observations, verified by autopsy, have brought this work to a degree of refinement in method not hitherto known. Contributions from time to time by workers in this country, most notably perhaps Jones and Fisher, of Philadelphia, have brought us to the realization that there is some clinical value to the.se tests. The text-book of Jones and Fisher, "Equilibrium and \'ertig(>." has been helpful in that it has stimulated interest in labyrinthine studies, but has gone far toward bringing all labyrinthine .studies into question by the wide and sweeping generalizations therein contained. The work of Griffith, car- ried on and published from the psychological laboratories of the University of Illinois has brought nuich of the work done by Jones anrl Fisher, as well as the other workers associated with the .\\'iation Ser\)cr during the war, into question. In as much as the study of dizziness is largely a study of the mechanism which controls body balance, any discussion of this subject must be largely ' of a physiological nature. It is the study of a new special sense which must be added to our study of the special senses of hearing, taste, touch, smell, sight and muscle sense. This new sense we must call the kinetic-static sense, or the sense that appreciates head motion and head position, and which thus in a sense appreciates body motion and body position. This sen>e has as its Page SW M. F. McCarthy end organs the labyrinthine portions of the internal car, and these end organs have as their sole function an im])ortant role in the maintenance of balance. The term "end organ" is used for the very special purpose of emphasizing the fact that the internal ear is an end organ and nothing more and that any study of the disturbances of balance must take into considera- tion not only the end organ but the nerve pathways by which its messages reach the central nervous system. Also it must deal with the method of the distribution of these messages and their attendant reactions, so far as they are known. Perfect equilibrium is maintained by the correlated activities of the spe- cial senses of sight, muscle sense and the kinetic-static sense. Vertigo can be caused by disturbances of vision and by a loss of the proper ocular muscle balance. This type of vertigo is ordinarily set right at once by properly fitted glasses and can be recognized by the fact that it is not present when the eyes are closed. Muscle sense when decreased, absent or perverted may decidedly interfere with equilibrium but does not cause dizziness. By far the largest number of those complaining of the most disturbing symptom of dizziness are those who have sustained some loss of or irritation to the kinetic-static sense either in its end organs, the labyrinths, or to some por- tion of their nerve pathways. As physicians we are too often given to loosely considering the ear as an organ such as the heart or the liver, forgetting that the ear is only the end organ of two very complex nerve pathway systems, the one having to do with the acoustic function and the other making possible the knowledge of the position and motion of the head. In as much as these two sets of fibers travel in the same nerve sheath as far as the point where they enter the medulla, the tests of hearing are of considerable value in giving some idea of the state of the eighth nerve at least as far as the point where it enters the medulla. For many years the hearing tests were the only means by which the condition of the vestibular fibers might be ascertained, it being reasoned, with some foundation, that any condition affecting one set of fibers, in the same nerve, should aflfect all the other fibers in that nerve. The difficulty here encountered is that later observation has taught that this is only partially true. For some reason not entirely comprehended, the fibers having to do with hearing are much more sensitive to the actions of toxins and much less hardy when subjected to pressure or like injury. Under such conditions the first fibers to cease to function are the acoustic .ibers, and often we have tested cases in which the acoustic function has jeen completely lost but in which the vestibular fibers were still functioning. The explanation offered for this phenomenon is that in the scale of animal development the last functions to be acquired are the least hardy and re- sistant to attack, the sense of hearing being acquired long after the kinetic- static sense. However, the tests of hearing do turn some light upon the state of the vestibular fibers, but, what to most of us is more important, is RANSOM OFF MEMORIAL VOLUME that tests of the vestibular fibers give us an insight into the condition of the acoustic fibers. If we are to search for the causes of dizziness then we must inquire into the state, first, of the labyrinthine portions of the inner ears, and second, their respective nerve pathways. So we are brought directly to an inquiry into the function of the labyrinthine portions of the inner ear. Just as the child's first vision is upside down and the higher brain centers learn to in- terpret the inverted image, so when the first head movement occurs and the endolymph of the semi-circular canal moves, the higher centers of the brain learn to associate that endolymph movement in one direction as indicative of head motion in the opposite direction. So. too, when the head is rapidly turned from one side to the other, the higher centers in an eiTort to stabilize the sensorium, make the eyes lag behind a little during the turn and cling to the objects as they pass. This lagging behind is the slow component of nystagmus. As the eyes give us some new object to which they are clinging during the turn, they are brought up with a sharp snap to seek some new object and this is the rapid component of nystagmus. This explanation, as ofifered by Jones, seems somewhat plausible, and whatever explanation we desire to accept w-e do know that movement of the endolymph in one direc- tion in the semi-circular canals has become associated with a slow eye movement in the same direction and a rapid eye movement in the oppo- site direction, the slow eye movement being the direct result of stimula- tion from the semi-circular canals. That the higher centers, most prob- ably in the cerebral cortex, are responsible for the rapid component of nystagmus seems to be borne out by the fact that the rapid component is not present in induced general anaesthesia or in destructive lesions of the cerebral cortex. A'estibular irritation, under such conditions, results in eye movement in the same direction as the endolymph movement, but the rapid 'component fails to materialize and the eyes are deviated in this direction as long as the vestibular irritation lasts — conjugate deviatien. Long years of experimental work on the labyrinths and gradual accumu- lation of clinical evidence has brought us to the almost certain understanding that it is through constant messages through the semi-circular canals that balance of the body is ordinarily maintained, for it is thus that the higher centers realize head position and head movement. Since balance is in a large measure dependent upon this knowledge of head position and head movement, anything that disturbs the mechanism which makes this knowledge possible, disturbs the sense of balance or the kinetic-static sense and dizziness results. Then, too, we have come to know that the labyrinths are constantly sending messages to the nuclei controlling the eyes muscles and maintaining for the eye muscles a sort of tone or bal- ance. We know this to be true as any irritation to or cessation of function of either labyrinth immediately results in nystagmus, which has a definite direction and type varying with the labyrinth affected. For example: In- jury or irritation to the right labyrinth results in a slow movement of tlie Page .?}8 M. P. McCarthy eyes to the right and a rapid eye movement to the left, this being known as nystagmus to the left and vice versa. Knowing that loss of function of a labyrinth or irritation to it or its associated pathways is accompanied by dizziness or nystagmus, or both, by the analysis of these two symptoms we have a method of arriving at some conclusion concerning the cause and its location. In the analysis of dizziness one must consider the direction and intensity of it as manifested by the so- called act of past pointing. When the eyes are closed and one is having the subjective sensation of turning, if the finger is put upon an object and then lifted into the air, when the finger is brought down to find the object again, instead of finding it the finger points past it to the right or left, depending upon the direction of the subjective sensation of turning. If one feels that he is turning from right to left he feels that after having once touched an object and raised his finger from it, that the object has moved past him to the right, and so when he again attempts to find it with his eyes closed, he points past it to the right, or, as it has come to be termed, past points to the right. Bimanual past pointing as measured in inches gives some indication as to the intensity and direction of the vertigo. Since the vertigo has re- sulted from some irritation to or destruction of the labyrinths or their path- waiys, past pointing gives some insight into tlie state of these end organs and their fibers, as well as throwing some light upon the nature of the stimulus or lesion and its possible location. Past pointing in itself is only a small aid to diagnosis and to this observa- tion must be added other observations before even a conjecture is war- ranted. Past pointing is probably less important as an observation than the analysis of nystagmus, for the absence of nystagmus after labyrinthine irri- tation is always pathological, whereas the absence of past pointing may in- dicate a pathological condition or it may not. However, presence of past pointing in both directions with both hands, elicited by the use of the caloric tests, is strong evidence that the cerebellar hemispheres are intact and such an observation certainly has its value. It is not the purpose of this paper to attempt to cover the more detailed portions of the analysis of labyrinthine responses to stimulation. Rather it is the purpose to discuss the basic principles of the tests of labyrinthine function as brought out by the efforts of many workers since interest first began in this question. With the head at thirty degrees forward, the plane of the horizontal semi-circular canals is parallel with the floor, and when the body is rotated with the head in that position, it is claimed the only endolymph movement is in the horizontal canals. Therefore, we know that any resultant response given in the form of nystagmus or past pointing must come from the endolyph movement in the horizontal canals. The greatest objection to the turning tests is that both labyrinths are stimulated at the same time. If the lesion should be unilateral and not complete, the value of the turning tests is almost nothing. For reliable diagnostic purposes there is only one set of tests of real RAXSOHOFF MEMORIAL VOLUME value and these are the so-called caloric tests, in which one ear at a time is douched with water cooled to sixtj-eight degrees Fahrenheit. By this method, by altering the position of the head, each set of canals can be tested separately and each variation in the normal responses, in intensity, direction and duration of nystagmus and the amount and direction of past pointing be observed and recorded. With the head at thirty degrees forward, the horizontal canals are parallel with the plane of the floor, and the plane of action of the vertical canals is at right angles to the floor plane. When water at a temperature of sixty- eight degrees Fahrenheit is run into an external auditory meatus, with the head in this position, the bone immediately adjacent to the labyrinth is chilled and the specific gravity of the endolymph, rising at the chilled point, a cur- rent is started downward toward the ampulla in the vertical canals only. The fluid in the horizontal canal remains unmoved as it is parallel with the plane of tlie floor and no force of gravity is in action on its endolymph. r.y varying the position of the head from thirty degrees forward to sixty degrees Imckward, we place the plane of action of the vertical canals parallel with the floor and now the horizontal canals are at right angles to the floor plane. At once the endolymph of the vertical canals comes to rest and the current, if it is such, begins to move downward away from the ampulla in the horizontal canal. By this means we are able to test each set of canals separately without having to resort to head motion to set up our endolymph currents, the same responses being given in past pointing and nystagmus a; though head motion had occurred in a direction opposite to the direction of the endolypmh current or flow. \\'hile variations do occur in cases where, due to drum thickening or bone changes, the chilling of the canals is de- layed, the average patient, following douching of an ear with water at a temperature of sixty-eight degrees Fahrenheit, will exhibit the ocular move- ments characteristic of nystagmus in from forty to sixty seconds from the time the douching is begun. Forty seconds was the titne as set by Jones in his review of many thousand tests made on aviators during the war. How- ever, our tests on the average clinical patient have shown that this figure is a little low and that it is more apt to be fifty to sixty than it is forty, and often may run over, that in cases that do not exhibit any marked drum changes. Some of these patients have been douched several times with the same results and have been followed for over a year without exhibiting the slightest suggestion of any pathological changes in either the acoustic func- tion or the kinetic-static sense. However, the thousands of tests being done and to be done in the future will settle such questions very definitely within the next decade. If the douching of an ear is continued until the ocular movements reach a maximum, there should be present past pointing with both hands in the same direction to the side of the ear stimulated. This past pointing may vary somewhat in amount, the reaction being somewhat mure marked in some people. Since this past pointing is in a sense an indication of the Page SSO M. F. McCarthy amount of dizziness, we ordinarily expect it to be present in continuous and well-defined vertigo. Providing there is not some lesion of the lobes of the cerebellum which will interfere with the synergy of the arms as the eli'ort is made which results in inward or outward pointing of the arms, this past jiointing should be bilateral. When we remember that in the caloric tests, done by douching the ears, we are testing each set of canals separately, as well as their associated nerve pathways, the significance of the tests becomes apparent. In the last few years it has become fairly well established that the fibers from the vertical and horizontal canals do not follow the same paths after the fibers of the eighth nerve have entered the upper portion of the medulla. The paths they pursue, as at present understood and upon which understanding suc- cessful localizations are being made, is that the fibers from the horizontal canals dip down into the medulla and end in Dieter's muclei. From there, fibers pass to the posterior ground bundles which join up the nuclei of the nerves controlling the eye movements exhibited during nystagmus. The greater part of the remaining fibers pass into the inferior cerebellar peduncles of their respective sides and so reach the cerebellar nuclei. On the other hand, immediately upon entering the upper portion of the medulla, the fibers from the vertical canals pass upward and enter the pons, where they terminate in some homolateral nuclei as yet not certainly known. These nuclei are also linked up to the pontine nuclei controlling the eye movements, by fibers which pass to the posterior ground bundles. The greater part of the remaining fibers reach the cerebellar nuclei by way of the middle cerebellar peduncles of the same side. Hence, it is said by testing the horizontal canals we are testing not only the integrity of the canals themselves, but the integrity of the upper portion of the medulla, the inferior cerebellar ])eduncles, and the homolateral cerebel- lar nuclei. So, too, by testing the vertical canals of one side, we test also the integrity of the lower and lower middle portions of the pons, the middle cerebellar jjeduncle and the cerebellar nuclei of the same side. Since it is by means of the superior cerebellar peduncles that the cerebellar nuclei are joined to the higher centers in the cerebral cortex, where take place the complex associations of stimuli necessary for the knowdedge of motion of the head or of its position in space, we are given some information concern- ing the state of the tracts of the superior cerebellar peduncles themselves. Since with our tests we are given some information concerning the activi- ties of the fibers traversing such important structures as the medulla, pons, the cerebellar peduncles and hemispheres, as well as the higher cerebral centers from which originate the arm movements having to do with past pointing, their importance warrants consideration. Nor is this importance lessened by the fact that in some measure the condition of each of these structures can be estimated separalelx-. ( )ur interest in this work has come nut from ;iny desire to enter upon a career in neuro-otology, but rather from a desire to find some means of RAXSOHOFF MEMORIAL VOLUME throwing light upon the condition of the internal ears in all too numerous cases of hopeless deafness that have come into our hands. Then, too, we have been seeing more and more patients complaining of dizziness in which we felt the integrity of the internal ears was established. Since no examina- tion of the internal ear can be complete without having considered the state of its nerve tracts as well, there is no choice for the otologist who is con- fronted with the necessity of attempting to find the cause or causes or re- current dizziness in one of his patients. All the light that neurologists, with whose collaboration this work should always be done, can throw together with that of otological observation, is only too often too feeble to allow us to see clearly to the cause and so be guided to the relief of the suffering patient. There is no doubt that most of the cases of dizziness which we see are due to affection of the internal ears or their immediately adjacent nerve supply. The difficulty may be occasioned by some disturbance of the blood supply to the parts, anaemia or hyperaemia, or to the presence of some toxic material which has reached these structures either through the blood or lymph chanels or by the simple diffusion or toxic material through the bone, as can happen in purulent infection of the middle ear. These cases, once the toxic material is eliminated or the circulatory disturbances set right or the middle ear drained of the pus, promptly recover. However, we must be constantly on our guard for the cases of persistent dizziness or for those cases which recur at frequent intervals and in which there is some question as to whether means taken to combat the cause is being effective or not. We must not forget that it may not have been our remedial measures which re.sulted in the cessation of dizziness, but that it may simply mean a cessation in the amount of local or general nerve pressure. Nothing is more perplex- ing than, in cases of known central lesion accompanied by a rise of intra- cranial pressure, to find that one day a set of fibers are working and the next day to find their function totally lost, to be in turn followed by almost complete recovery of function within the following twenty-four hours. In- tracranial pressure as manifested by inhibition of nerve action is certainly an extremely variable quantify and marked and prolonged remissions of symptoms are often found in even the most serious of intracranial lesions. It is these remissions which lull us so often into a false sense of security in the early observation of patients complaining of dizziness and the patient is dismissed from observation as having been the victim of some unknown type of toxaemia which has passed away. We must remember that dizziness can result from any disturbance to function of the semi-circular canals or of their nerve pathways to the cere- bral cortex. The stomach itself is not the cause of dizziness except as a hyperacidity may influence the (|uanlity or quality of the blood supplied to these parts, h'ocal infectinn from leedi or tonsils, constipation, diabetes, nephritis, tumor masses, and so forth, only cause dizziness as they destroy parts of or upset the workings of these balance control systems. M. f. McCarthy Every disturbance of these systems is immediately attended by dizziness or nystagmus, or both. If complete destruction of one of these balance con- trol systems has taken place, as may occur in the destruction of the internal ear of one side or the complete degeneration of an eighth nerve, this dizziness may persist in the most severe form for weeks, attended by an almost con- stant ny,stagmus of a type that varies in its nature according to the ear or nerve afifected. Gradually, in this form of disturbance to the kinetic-static sense, the re- maining system takes up in part the function of the one lost and the higher centers learn either to ignore the disturbing stimuli coming in over nerve pathways from the destroyed area or to rely upon the remaining system re- enforced by the knolvledge of the body's position in space by the muscle and visual senses. The past pointing and nystagmus present in such dis- turbances, resulting as they do from some stimulus or lack of stimulus from within, are termed spontaneous past pointing and spontaneous nystag- mus to differentiate this type from that resulting from external ^imuli, such as are used in the caloric and turning tests. There are two types of spontaneous nystagmus to be observed — the rhythmic, in which it is possible to distinguish a slow movement in one direction associated with a rapid movement in the opposite, and the os- cillating type, in which both movements are of equal rapidity. Tlie oscil- lating type has no relationship whatever with the disturbances of the kinetic- static sense, and is due entirely to either an early acquired or con- genital central visual defect. This type of nystagmus becomes much more marked whenever visual fixation is attempted and can be differentiated with relative ease from the rhythmic. Close observation of the rhythmic type will disclose to which side the rapid movement or component is taking place, and if, for example, it is to the right, then the nystagmus is said to be to the right. Rhythmic nystagmus resulting from the complete cessation of func- tion of one or the other of the balance control systems, has a mixed rotary and horizontal movement to the slow component. When it results from a disturbance to the vertical canals or their nerve supply alone, the nystagmus has a rotary element alone as its slow com])onent. When, however, the dis- turbance affects the horizontal canals or their related nerve supply, the slow component is entirely horizontal. So it is that the analysis of spontaneous rhythmic nystagmus gives us often very important clues as to the type and location of the disturbance in function that is resulting in dizziness to the patient. Spontaneous rhythmic nystagmus upward or downward is prac- tically always indicative of pontine pressure. The difficulties attending constructive work in this field are manifold. Cases of this type progress so slowly that many observations made on those who are in the early stage of the development of their lesions are never followed by later observations. In a semi-invalid state they drift from ono ])hysician to another and often are completely lost for the opportunity of further study. This work is still in the active phase of discovery and prog- Pagc .X),; RANSOHOFF MEMORIAL VOLUME ress and nnich will be adderl in the future which will be of great benefit to humanity. I have no desire to paint the picture in too glowing terms, for the diagnosis of many of these conditions is a matter of prolonged and painstaking observation. In many, many cases we fail to make a diagnosis due to obstacles which we have not yet been able to overcome. There is no doubt that the tests have been overrated by some over-enthusiastic workers who, in a measure, have brought the tests into a certain amount of disrepute. There is no doubt, however, that this work has its very positive field of usefulness and that the future will see much added in the improvement of technique and a widening of its breadth of service. I wish to take this opportunity to thank Dr. Louis Fisher, of Philadel- phia, for his kindness in allowing me the privilege cff reviewing his case records. I wish also to express my appreciation for the kindness of Dr. Bentley and Dr. Coleman Griffith, of the Psychological Department of the University of Illinois. I wish to express my admiration for the accurate and monumentarwork being carried on in their laboratories for the purpose of advancing our knowledge of labyrinthine physiology. THE PINEAL GLAND.* THE PINEAL GLAND'S LNFLUENCE UPON GROWTH AND DIFFERENTL'\- TION WITH PARTICULAR REFERENCE TO ITS INFLUENCE UPON PRENATAL DEVELOPMENT. Carey Pratt McCord, M. D., Detroit. L L\TUODUCTIO.\" (A cursory review of recent work pertinent to pineal functioning.) The evidences that hnk the pineal body with a glandnlar function are much less definite than for such glandular organs as the thyroid, hypo- physis, ovary, and the suprarenals. Doubt is frequently expressed that the pineal body is more than a functionless vestige of what was once, in earlier evolutional stages, a functioning eye. Other observations have led to the contention that the pineal, through metamorphosis, has become a highly spe- cialized tissue that serves the body in a manner coinparable with the major members of the endocrinous system. The purpose of the present paper is to group the essential findings from the recent literature into a concise, unbiased resume, adequately expressing the status of the pineal body as a functioning organ. To this are added the writer's more recent observations upon the growth of young animals under the influence of pineal materials. ANATOMY AND EMBRYOLOGY (Bibliography numbers 1-57) The pineal body (pineal gland, epiphysis, conarium) is situated in the brain just beneath the splenium of the corpus callosum. (Fig. 1.) It lies suspended between the anterior quadrigeminate bodies. The gland is con- sequently just above the Sylvian aqueduct. The internal cerebral veins lie above and partially encircle the pineal. In the human the pineal is nearly trilateral in shape, in sheep is round, in cattle is oval. The average weight in cattle is .2 grams and in sheep .13 grams. Primarily the pineal is developed as a thin ependymal diverticulum from the diencephalon, extending between the posterior and habenular commissures. At a later stage this diverticulum thickens and encloses some of the adjacent vascular mesoderm to form the mature organ. (Streeter.) In those publications cited in the bibliography as pertinent to the anat- omy, embryology, and histology of the pineal, the studies have, for the most part, been prosecuted toward establishing (1) the presence of glandular tissue; (2) the presence of contractile tissue supporting the view that the gland is a valve regulating the flow of cerebrospinal fluid; (3) nerve fiber communication between this gland and other parts of the brain; (4) evi- dence of involution changes in the gland indicating a cessation of function. • From the Transactions of the American Gynecological Society, 1917 RAX son OFF MFMORIAL I'OLUMF These ])ul)licatinns may be summarized as indicating: (1) Complete cytologic studies in several species allow the inference that the pineal body is glandular in nature. The glandular elements, however, are few and illy defined. (2) The occasionally demonstrated muscle fibers in the pineal are without significance to pineal function. (3) Nerve fibers and neuroglia arc to be found at least in certain animals, but these are probably of trivial import. (4) The gland undergoes involution changes, beginniug in the human as early as the seventh year. Involution is pronounced at puberty. The degeneration is, however, not complete and the histologic picture of the adult gland is not such as to remove the ]:)ossibility of a continued function in adult life. PIXEAL XHt)Pr,.\SMS .\.\D KESULTIXG FUXCTIOX.XI, i:)lSTUI^B.\XCES ( Bililiography numbers 100-189) Tumors of the pineal are not of frecjuent occurrence. Tlic total num- ber of authentic cases, with subsecjuent necrojisy findings in some, is not more than seventy. These cases have been the source of the greatest infor- mation as to the functions of the pineal. In 1898, Heubner described a boy of foiu- and one-half years who showecl a precocious sexual and somatic growth. The body of this boy was that of a boy of eight or nine years. The genitalia corresponded to the proportions found at puberty. The pubic hair was 1 cm. long. A year later at autopsy a teratoma of the pineal was dem- onstrated. By 1907, Marburg was able to collect fort\- histories of such types. He sought to establish a clinical entity for pineal dysfunction. The term "Macrogenitosomia prfecox" has subse(|uently designated this condi- tion. In a more recent paper. Marburg attributes to the condition tlie following characteristics : 1. General. These include all the usual signs of intracranial pressure, usually secondary to a subsequent internal hydrocephalus. 2. Neighborhood. These for the most part are dependent upon en- croachment upon the quadrigeminate bodies, leading to diverse oculomotor paralyses and pupillary disturbances, and encroachment upon the cere- bellum, with ataxic manifestations. 3. Constitutional. Under this designation are grouped tiie manifesta- tions attributable to the derangement of the pineal glandular function. This constitutional syndrome consists of first, early sexual maturity, evidenced in the enlarged sex organs, pubic hair, general body hair, early change in voice ; second, precocious mental development, evidenced in the maturity of thought and speech ; third, general body overgrowth to the extent that a child of five or six years may have the appearance of a child of eleven or twelve. Frankl-Hochwart similarly has summed up the characteristics of this pathologic state. He states. "When one finds in a very young individual, along with the general sympionis of tumor as well as the signs of a lesion of the cor])ora quadrigemina. alinorm.-il body growlli, unusual growth of Hasir :!r.i: CAREY PRATT McCORD hair, adiposity, somnolence, ]ireniature genital and sexual development, and finally intellectual maturity, one must think of pineal tumor." Of the seventy cases at the present time available in the literature, only twenty-five occurred prior to puberty. Because of the pineal involution that occurs by the time of puberty, only in these twenty-five cases are consti- tutional manifestations to be anticipated. It is significant that with two exceptions all cases occurred in boys. Many cases of pineal tumors before puberty manifest none of the signs of precocity of development that are so striking in a few selected cases. A study of the clinical material reveals how little consideration has been given to the possibility of pluriglandular involvement. In fact, some early cases Fig. 1— Sagittal section of htef showing size, position, and relation of pineal gland. the necropsy demonstration of a pineal tumor led to the association of all prior metabolic changes to pineal functional perversion. This grew out of the prevalent conception of each endocrine gland as an entity entering into no interrelations with other similar organs. Judging these cases in the light of recent advances in pituitary pathology and physiology, it is difficult to delineate the manifestations of pure pineal derangement from a pluri- glandular condition. Gushing has pointed out that from the intracranial alterations attending pineal neoplasms, the hypophyseal functions are read- ily deflected from the normal. This infrequent condition in which the growth and dififerentiation into the adult is so' deviated from the normal that very young children acquire ratic r,7 RAN son OFF MFMORIAL VOLUME in part the sexual, mental and somatic characteristics of maturity, has nat- urally led to diverse attempts to induce such a condition experimentally. Through the extirpation of the pineal, through the feeding of pineal sub- stances to young animals, through the intravenous and subcutaneous admin- istrations of pineal extracts, has information been sought as to the signifi- cance of this organ in the body's economy. The outcome of such investiga- tions are described in subsequent paragraphs. EXTIRPATION' OF THE PINEAL GLAND (Bibliography numbers 71-78) Situated near the center of the brain, the inaccessibility of the pineal has prevented any widespread use of this method. The trauma is neces- sarily severe and until the recent reports by Dandy (1915) and Horrax (1916) the mortality has been very high — seventy-five deaths out of ninety- five operations in one series, and twelve deaths out of fifteen operations in another. With so high a mortality it may be questioned whether the few- survivors would exhibit constant changes referable to pineal deprivation. The mortality is usually due to hemorrhage into the ventricle from injury to the central cerebral veins, or to direct injury to the quadrigeminate bodies or adjacent brain tissues. Dandy has recently developed an operative pro- cedure whereby much of the trauma is obviated. The essential innovation lies in an approach through section of the splenium of the corpus callosum thus permitting freer manipulations in the operating field. Although the mortality may thus be reduced, the results obtained by Dandy, on com- parison with those obtained more recently by Horrax, are uniformly dis- similar. The respective summaries of these two investigators quoted below indicate how incomplete are our available data bearing upon extirpation as a method of approach to the problems of pineal function. Dandy states : "1. Following the removal of the pineal I have observed no sexual precocity or indolence, no adiposity or emaciation, no somatic or mental precocity or retardation. "2. Our experiments seem to yield nothing to sustain the view that the pineal gland has any active endocrine function of importance either in the very young or adult dogs. "3. The pineal is apparently not essential to life and seems to have no influence upon the animal's well-being." These negative findings are in keeping with the earlier work of Exner and Boese, and Biedl. Subsequent to Dandy's publication an extended report has been made by Horrax, whose positive findings are in keeping with those of Foa and Sarteschi. Horrax states: "L Total experimental pinealectomy is possible in guinea-pigs and rats. "2. Pinealectomized made guinea-pigs show a hastened development of the sexual organs, manifested before maturity by a relative increase in size and weight, both of the testes and seminal vesicles, over control pigs of the same litter. "3. Histologically the testes and seminal vesicles of these animals, if taken before the age of sexual maturity, show a more advanced physiological state than their con- trols. "4. The pinealectomized females appear to show a tendency to breed earlier than controls of the same age and weight. Page 35S CAREY PRATT McCORD "5. For several reasons, young rats are likely to prove better subjects for experi- mental pinealectomy than young guinea-pigs, and some evidence of hastened maturity has been obtained in this species." IMMEDIATE RESULTS FOLLOWING THE INTRAVENOUS OR SUBCU- TANEOUS ADMINISTRATION OF PINEAL EXTRACTS (Bibliography numbers 58-70) Unlike the intense cardio-vascular action of suprarenal extracts, or the uterine contracting action of pituitary extracts, the immediate results from intravenous or hypodermic injections of pineal extracts are not pronounced. Fig. 2. — /\ comparison of the effect on surviving guinea-pig uterus of pituitary and pineal-gland extracts. The height of contraction from the pineal extract admin- istered at B is trivial in comparison with the contraction at A induced by the much smaller quantity of pituitary extract. Time in minutes. Such phenomena as decrease in arterial tension, dilatation of the blood ves- sels, altered amplitude and rate of the heart beat, diuresis, glycosuria, and uterine contractions have been reported and confirmed. Under experimen- tal conditions the contraction produced in the uterus by 1 cc. of 20 per cent, pineal extract is much less intense than the contraction produced by 1/200 cc. of 20 per cent, pituitary extract. (Fig. 2.) The intensity of these sev- eral activities is so slight that at the present time only technical importance may be attached to these findings. FEEDING EXPERIMENTS WITH PINEAL GLANDS (Bibliography numbers 79-87) The syndrome of precocious development seen in the human is usually interpreted as the outgrowth of pineal deficiency — a hypopinealisni. Such being the case, if the feeding of pineal materials determined any changes, a state just opposite that cited above would be anticipated — a condition of deferred sexual, mental and somatic maturity. Curious to record, feeding experiments lead to rapid sexual and somatic development. Dana and Berkeley fed pineal materials to young animals (kittens, rabbits, guinea- pigs), and noted a 25 per cent, excess in weight over controls. These investigators sought to determine the extent of stimulating influence upon children of low mentality. Fifty feeble-minded children were treated and suitably controlled with other children of the same age and diagnosis. Binet tests were the criteria of mental advancement. No physical changes resulted but on prolonged treatment the mental development was greater than that prior to treatment and in excess of control children of the same Page !i.W RANSOHOFF MEMORIAL VOLUME mental age. These studies on feehlc-niinded children afford certain technical evidences of value but the quantity of improvement resulting is not sufficient to warrant any widespread use of pineal materials as a profitable treatment of feeble-mindedness. Hoskins (1916) in feeding experiments upon albino rats, studied the inHuence upon the growth of the various ductless glands including thyroid, thymus, hypophysis, and pineal. His results would indicate that none of these glands have any constant effect upon the growth-rate of young rats. McCord (1914, 1915) employed 400 young animals (chickens, guinea-pigs, dogs) in experiments to establish the extent of influence the pineal exerts upon growth and development. He concludes from his experiments that the same precocity of develop- ment usually attributed to pineal deficiency (hypopinealism) was obtained in animals by supplying an increased amount of pineal substance by feeding or injecting pineal preparations. Such administration of pineal substances led to a more rapid growth of body than normal, and determined an early sexual maturity. The excess in rate of growth was most pronounced (40.9 per cent, excess in eleven weeks) in young animals fed with pineal tissue obtained from young animals, Xo tendency to gigantism has followed pineal administration. After maximum size was attained, pineal administra- tion appeared to be inefi'ective. Both males and females respond to the influence of pineal substances in rate of growth, but the response has been more definitely mani- fested in males. II. THI-: PIXR.M, C.L.AND'S INFLUENCE UPON GROWTH .AND DIFFERENTI.ATION (.\ record of experiments upon postnatal and embryonic growth-differentiation processes) In the developmental processes inaugurated at conception two distinct phases are to be observed — growth and differentiation. In intra-uterine life differentiation into specific organs and tissues is the essential process. In pre-adult life, growth proces.ses are dominant. At puberty differentiation again asserts its influence. In adult years both these developmental pro- cesses are less in evidence, a condition we commonly designated as maturity. These two phases of development are necessarily intricately interrelated, but within certain limitations may be separately altered. Traces of thyroid tissue added to the water in which tadpoles live will bring about the com- plete transformation of the tadpole into a minature frog within one week, whereas normally this metamrophosis consumes from four to six months. (Gudernatch.) This phenomenon is due to the intense differentiative action of the thyroid. Similarly thymus tissue retards differentiation of tadpoles. At the period of development wherein normally tadpoles begin to differen- tiate, thymus fed tadpoles continue to grow larger without differentiation. Manifestly both these factors in development are ultimately dependent upon the quantity or quality of cell activity. In our earlier records of the influence e.xerted by the pineal upon devel- opment we employed young animals and chicks. \'ariations were intro- duced to reduce the possibility of incidental error in dosage, in method of administration, in source of materials, in age of the test animals. \\'ith the exception of two series we have uniformly found that young animals who had been fed (or injected) pineal materials have outgrown their controls of the same age. (Fig. 3.) In one series the difference was 40 per cent, at eleven weeks of age. No tendency to gigantism was observed. As the nor- mal adult size was approached the stimulative action of the pineal was no longer effective. The testes of certain of these rapidly developed guinea CAREY PRATT McCORD pigs were examined in comparison with controls. Grossly the testes from pineal fed animals were SO per cent, larger. Microscopically the cellular elements were far in advance of controls and were characterized by very active spermatogenesis. The females gave birth to young when the con- trols were in the middle third of their gestation. At first it was thought this might be evidence of a shortened gestation period, but more carefully scrutinized experiments determined that this was the outcome of earlier breeding, due to an earlier maturity. At all times this type of feeding experiment is open to the error that normally such animals exhibit very appreciable individual variations. We have anticipated that less complex life forms that show scant individual variations even in large numbers would afford acceptable data as to any action that pineal extracts might have on their growth-differentiation pro- cesses. For the purpose, we selected (1) paramoecia (paramoecium cau- datum), a unicellular organism that through transverse fission may divide into many generations in a single day, (2) tadpoles) of frogs and toads. This larval form of the frog and toad corresponds in many respects to embr\onic intrauterine life in higher animal life. PAR.AMECIUM EXPERIMENTS Cultures were maintained in the laboratory, growing on hay infusions. These organisms are aljout '4 mm. in length and may be readily counted with the naked eye. Through transverse splitting reproduction is accomplished. Under standardized conditions the rate of divisions is relatively constant. It will be argued that in the event of constant exceptional variations in the number of generations formed when pineal materials were added to the culture medium and not occurring when other similar protein materials were introduced, that the phenomenon is attributable to pineal activity. The following procedures were employed. A single paramcecium was isolated until the reproduction of the third generation. These resulting four individuals were separated and placed in difTerent media (a) one in hay infusion; (h) one in a hay in- fusion extract of desiccated pineal gland, .05 per cent, strength; (c) one in a hay in- fusion extract of desiccated muscle of equal strength as a control material; (rf) the Tabu I. Records of Divisions of Paramoecia 6 7 8 9 10 II 12 1.^ 14 15 16 17 Average 'ineal Muscle No. of Hay Pineal Muscle ■,l.i„rt. Tissue. Kxpe'm't. Infusiuu. Gland. Tissue. ^^ 18 13 31 19 6 12 20 1! 19 s 21 s 2 16 22 8 8 1.^ 2} 16 4 12 24 8 5 19 12 JS 10 17 10 12 26 ] 1 19 12 4 27 7 5 9 4 28 4 3 7 6 29 7 9 19 16 30 8 2 21 1 ' 31 15 s 25 23 30 10 22 11 RANSOHOFF MEMORIAL VOLUME fourth one was a variable control. These cultures were maintained in a moist cliamber for a fixed period (48 or 24 hours). At the expiration of that time the several cultures were examined as to the numbers of reproductions. Almost invariably the divisions were more numerous in the pineal culture. For example, in one 48-hour experiment 12 individuals resulted from the plain hay infusion, 30 individuals from the hay in- fusion pineal extract .05 per cent, and 10 individuals from the hay infusion muscle extract .05 per cent. The results from 31 consecutive experiments are grouped in table 1. The inference is. that pineal materials, when added to the culture medium of the unicellular orgaiusm, ])arama"cium, determines a more rapid rate of reproduction. (Fig. 4). TADPOLE EXPERIMENTS. The time of appearance of the successtive stages in the differentiation of tadpoles into frogs is an excellent criterion of the influence of any Fig. 5. A comparison of luo groups of t..a.l tadpoles taken from the same lot, photographed simultaneously after two weeks of lalioratory feeding, (iroup to the right fed small amounts of desiccated pineal gland triweekly. Group to the left fed equivalent amounts of desiccated muscle tissue. variation in the living conditions of these animals. For the individuals of a single laying, fairly constant is the occurrence of such stages as the bud- ding of the hind legs with the subsequent formation of the different portions of the hind legs, the closing of the gills, the extrusion of the fore legs, the assumption of terrestrial life. Such are the phenomena we sought to influ- ence by the introduction of pineal gland materials into the living water of the tadpoles. About 50,000 frog eggs were procured and hatched in the laboratory. These were divided into colonies of about 200 each. In most cases these colonies were from the same laying. With so abundant materials it was possible to introduce wide variations in (est materials and controls. The CAREY PRATT McCORD pineal glands were fractionated into various components and tested against controls such as other endocrine glands, split proteins, histamine, lipoids, etc. Through photography and actual measurements the variations were recorded. The present paper can make but most casual reference to the accu- mulated results. The photograph and drawings will serve to indicate the trend of results. (Fig. 5.) (Type photograph — adjacent trays of pineal fed and muscle fed tadpoles of the same laying.) At this stage the pineal fed, while about double the size of the controls, show no tendency to dififer- Fig. 6. Drawings madt- at weekly intervals indicating the rate of inetamorphosis of Bufo Americana tadpoles fed pineal tissue in comparison with normal metamor- phosis, a to e inclusive, controls. / to /, pineal fed. The small figures to the right, of a, b, f and g, represent stages in the development of the hind legs for these respec- tive tadpoles. entiation. Ultimately, however, differentiation is earlier, as may be ob- served in the drawings of Fig. 6. It is our belief that the pineal gland contains some substance capable of stimulating growth and ultimately diiTerentiation in these larval forms. GENERAL SUMMARY. From the lack of unanimity in the literature any conclusions as to the details of pineal gland function must be made flexible rather than dogmatic. A survey of available data leads to the following summary as representing the present status of the pineal as an organ of internal secretion : RAXSOHOFF MEMORIAL VOLUME 1. A clinical syndrome is to be associated with disturbances of the func- tions of the pineal gland. Because of the involution of the pineal at puberty, the constitutional manifestations of pineal pathology appear to be confined to prepuberal years. The essential characteristics (apart from pressure and neighborhood manifestations) are (a) early sexual development evidenced in the enlarged genitalia, pubic hair, general body hair, early change in voice; (b) precocious mental development, manifested in maturity of thought and speech; (c) general overgrowth of body to the extent that a child of six or seven years may have the appearance of a child near puberty. 2. The experimental extirpation of the pineal gland is surgically pos- sible. The gland is not essential for the maintenance of life. The early symptoms following pinealectomy are attributable to the severe brain injury. No changes attend the removal of the gland in adult animals. As to the effects of pinealectomy in young animals, Sarteschi, Foa. and Horrax respec- tively state that the removal of the gland leads to precocity of development. Exner and Boese, and Dandy report no changes after pinealectomy. 3. The administration of pineal substances to young mammals is re- ]iorted to hasten growth and sexual maturity. In unicellular organisms (paramcEcia) pineal extracts increase the rate of reproduction to more than double that of controls. In larval forms (ranidae) both growth and differ- entiation are hastened as a result of pineal feeding. 4. The inference is allowable that the pineal gland is an organ of internal secretion who.se functions, however, are of minor significance in the general activities of the endocrinous system. BIBLIOGRAPHY. EXPn:RI.\IENT.AL .-\natomy and Embryology Beraneck, E. : Anat. Anzeiger, 1892, vii, 674. Anat. Anzeiger, 1893, viii, 669. Biondi. G. : Histologische Beobachtungen an der Zirbeldriise, Ztschr. f. d. ges. Neurol, u Psychiat., 1912, ix, 43. Bizzozero, G.: Centralbl. f. d. mcd. Wissensch.. 1871, "R. Istit. Lomb. di Sc. tt Lett." Milan. Cameron. .lolin: .Anat. Anzeiger, 1903, x.\iii. Proc. Roy. Sec, Edin., 1904, "Jladrid, Ramon y C'ajal: .\puntes para el studio del bulbo raquideo cerebelo - •■ OS, Sue. Es ..•-■-.- . - Conslantini. G. : Pathologica Cionini, A.: "Riv. Sperim. d. Fren. e. d. .Med. Legale," 1885-86, xi, 182; xii, 364. Cutore, (',.: Arch. Ital. di .\nat. e. di Embryol., Firenze, 1910, ix, 3-4. Darkschcwitsch. L. : Neurol. Centralbl,, 1886, v, 29. Dandy, A.: (>art. Journ. of Micros. Sci.. 1899, xlii. 111. Ibid. 1907, li. 1. Trans. Roy. Soc. Nervraxe, 1901, ii, 257. "^ " """ ''"' '"^'""" •=""■ Edinger, L. : Bau der nerv6sen Zentralorgane, 1908, Ed. 7, 203. d'Erchia, F.: Contributo alio studio della volta del cerebelo intermedio e della regione para fisaria in cmbrioni di Pesci e di Mamiferi, ilonitore zool. ital., 1896, vii. 118 and 201. Faivre, E. : Observations sur le Conarium, Compt. rend. Soc. de biol., 1854. Series 2, i, 195 Faivre. E. : Ann. d. sc. nat., 1857. Series 4, Zoologie, viiviii, 52. Fenger, F. : The Composition and Physiologic Activity of the Pineal Gland. Tourn. .\m. Med Ass'n, 1916. Ixvii, 1836. Flesch. M.: Anat. Annzeiger, 1888, iii, 173. Funkqvist, H.: Anat. Anzeiger. 1912, xlii. 111. Galasescu, P., and Urechia, C. T.: Les cellules acidophilcs de la gland pincale. Conipt. rend Soc. de biol., 1910, Ixviii, 623. Galen: De usu partiiim Corporis humani, \enice, 1562, viii. Galeotti, G. : Riv. di Patol. Nerv. e. Mentale, 1896-7, ii, 481. Gaskell, W. H.: On the origin of Vertebrates from a Crustacean-like .Ancestor. Ouart. Jour Micr. Sc, London, 1890, xxxi. Hagemann: "Archiv, von Rejchert u. Dti Bois-Reympad,'.' 1872. Hill, C: Jour, of Morpho!., 1891, v, 503. Ibid, 1894, ix, 237. Page^ SKi CAREY PRATT McCORV Hosk>ns E K The grox*th of the body of the Albino rat as affected by feedinK various duct- glands (thyroid thymus hypophysis and pineal) Tourn of Exp Zoology, 1916 xxi, 295 Illing P_ \ergl anat u h.stol Untersu,d Epiphysis etc ,I"-B- D-se^'-, L? P-^. '^O. ' Histng nesis of Pineal Pody of Sheep Am Jour. Rp ilts f Recent Studies of the Mammalian Epiph] 1 -'31 H ,„,,„. .. „ ...,„.«...■.-, .,.. .—. . .---- Anat., 11 II I Re erieux Certb o spinal 18 5 ckers Handbuch 1871 Clap 1 Z rbeldruse Pcrlin kin Wochsch 1911 \lviii, 1069. rt Rend d 1 Soc de Biol 190(1 In 87l t ng beim Studmn des Baucs del nerv sen Zentralorgaiie, 1 These de Bordeaux 1S80 87 C8 rebrale fanngea e la gHndula pineale in Patologia. etc.. ( 1 Lr Bau des men chliclien ( ehi ns Iei[zig 1859. Part 2. 0' Menschenhirn Stockholm 189f 54 . I herd e istologi che s ilia ghiandola | ineale Folia ncurobiol.. •hrblch der ^clrolcglC lilangen 1881 e Jei menschen Zirbeldiuse Zeitsc of the Paraphysis and Pineal Regie sur Genitale. Wi Dixon and Halliburton Proc Physiol Soc (To Howell W H The Plisiol gical 1 Sects of I> bule Body Joui Exper Med 1898 in ^-IS , , ^ r ■-..<• .i i.- i i, i Jordan H F an 1 Ejster J ^ E The Physiological \ction of Extracts of the Pineal Body. I°o"wy P Die Secretwege der Ziibeldruse Arb a d neurol. Inst. a. d. Wien. Univ.. 19IJ. Mackenzie, K Quart Journ of Exper Physiol 1911 iv M Novak, J.: Ueber Kiinstliche Tumoren der Zirbeldriisengegend, \\ len. klin. Wchnschr.. 1914. btt I and Scott, J. C. : The Action of Corpus Luteum and of the Pineal Body. Month. Cycl. and Med. Bull.. 1912, 207. , ,. , „^ . _ .. ,„,, Ott, I., and Scott, T. C. : Proc. Soc. Exper. Biol, and Med., 1910. Therapeutic Gazette. 1911, xxvii, 68. Therapeutic 'Gazette, 1912, xxviii, 310'. , , ,,,, PcIIegrine: Gli. effette della castrazione sulla ghiandola pineale. Arch. |i. le sc. nied., 1914, -Bouveret: Descartes et psvchoplivsiologie de la glande pineale, Nouv. 1913, XXV, 7119J, Adler: Extirpation der Epiphyse, \i I i 1 lungsmechn. d. Organ. 1914. xl. 1- Exner, A., and Boese, T. : Ueber . i i i^ii der glanduia pineale .\luiicheii. ined. Wchnschr., 1911, 154; Neurol. Centrall.l.. I . . Exner, A., and Boese, .1.: Deutsch /. h , h i . ,«.. 1910. cvii. 18J. Eoa. C: Hypertrophic des testlculfs et ile la crck- apres 1 extirpation de la gland pmcale chcz le co<|. Arch. ital. de biol., 1912. Ivii. 233. Eoa, C: Nouvelles recherches sur la fonction de la gland pineale. Arch. ital. de biol., 1914, Sarteschi, U. : Richerche istologische suIIa ghiandola pineale. Folia ncurobiol., 1910. iv. 675. Sarteschi. U. : Sindrome epifisaria macrogenitosmia priecox. Pathologica. 1913. v. 707. Dandy, W. E. : Extirpation of the Pineal Body, .Tour. Exper. Med.. 1915. xx.i. 2. Horrax, G. : \ide infra. Feeding Experiments Berkeley, W. N.: The Use of Pineal Gland in the Treatment of Certain Classes of Defective Children, Med. Rec, New York, 1914, Ixxxv, 513. Dana, C. I,., and Berkeley, W. N. : The Functions of the Pineal Gland, Med. Rec, New York, 1913. Ixxxiii. 835. Goc^tili. K.: The Influence of Pituitary Feeding upon Growth and Sexual Development. Bull. ments on Tadpoles, Am. Jour. Anat., 1914, xv, 431. zu V. Frankl-Hochwart, Verein f. Psychiat. u. Neu Pineal Gland. I, Experimental Observations, Archiv iiie. 1916. xvii. 607-626. dcCord, C. P.: The Pineal Gland in Relation to Somatic, Sexual and Mental Dev .•\m. Med. Assn., 1914, Ixiii, 232. Page 3tf5 RANSOM OFF MEMORIAL VOLUME McCord, C. P.: The Pineal Gland in Relation to Somatic, Sexual and Mental Dcvtlopmen No. II. Journ. Am. Med. Assn.. 1915, Ixv, 517. McCord, C. P.: The Pineal Cland, Interstate Med. Jour., 1915, xxii. .154. General Eenda: Deutsch. Klin., 1903. Biedl: Innere Secretion, Urban and Schwarzerbcrg, \ienna, 1913. Cushinp. n,: The Pituitary Body and Its Disorders, J. B. Lippincott Co.. 1912. Erdhcini: \\i : ll\ [i.^'liv^is, Akrcmegalie unc Kidd. I„ 1,: 'I Ik- I'.neal Body. A Revie Miinzer, A.: llic Zirbeldriise. Berl. klin. Wchnschr., 1911, xxxvii. 1. Vincent, S.: Internal Secretion and the Ductless Glands, 1912. Schiiller, A.: Lewandowsky's Handbuch der JCcurolgie, 1913, iv, 337. Marburg, O.: Zur Kenntniss der normalen und pathologischen Histologic der Zirbeldruse, .Xrb. a. d. neurol. Inst. Obcrsteiner. VVien. 1909, xvii, 217. Del Priere, N.: Modifications dans la pression Sanguine et dans I'accroissement somatique des lapine, a suite d'injections d'cxtrait de glande pineale. Arch. Ital. de Biol., 1915. Ixiii. 122. Clinical Askanazv. .M.: Teratom und Chorionephitheliom der Zirbeldriise, Verhandl. d. deutsch. path. Gesellsch., leua. 1906. 58. Bailey' and Telliffe: Tumors of the Pineal Body, The Archives Int. Med., 1911, viii, 851. Bartlett. F.'K.: Hypertrophy of Pineal Gland, The Archives Int. Med.. 1913, xii, 201. Biach .ind Hulles: Ueber die Beziehungen der Zirbeldriise zum Genitale. Wien. klin. Wchnschr.. 1912. Blane, G.: History of Some Cases of Disease in the Brain; Case of a Tumor Found in the Situation of the Pineal Gland, Tr. Soc. Imp. Med. and Surg. Knowledge, 1800, ii, 198. Blanquinque: Tumcur de la glande pineale, Gaz. hebd., 1871, 532; Lancet, London, 1871. Bourhnt, M • K'-^T'- du troisieme ventricule avec hydrocephalie des ventricules lateraux, Gaz. Ca'nii- \. ■ !..■; of Two Cases of Dilatation of the Central Cavitv or Ventricle of the Pineal Cl.ir , I I i i ^. c London, 1899, i, 15. Chirnn. , !■ I I.,,!! .M della glandula pineale. Med., ital.. 1907, v, 141. Coats. .(.; .\ii -\dciiuid Sarcoma with Cartilage Originating in the Pineal Gland. Tr. Path. Soc, London, 1887, x.Kxviii. 44. Gushing. H.: The Pituitary Body and Its Disorders. J. B. Lippincott Co.. 1912. Daly: A Case of Tumor of the Pineal Gland, Brain, 1888, x, 234. Duffin: Tumor Implicating the Corpora Quadrigemina, Clin. Soc. London Lancet, London, 1876, i, 888. Eberth, J.: Intrakraniellcs Teratom mesodermalen Ursprungs, Virchow's Arch. f. path. Anat., 1898, cliii, 71. Esteves and Beatti: Klinisclie und anatomische Studien eines Epithelioms der Zirbeldruse, Arch, de Pedagogia de la Plata, 1909. Falkson, R. : Ein Chondrocystosarkom im dritten Ventrikel, V'irchow's Arch. f. path. Anat., 1879, Ixxv, 550. Feilschenfeld: Ein Fall von Tumor cerebri (Gliasarkom) der Zirbeldriise Neurol. Centralbl., 1885, iv, 409. Fnrster: Ein Fall von Markschwamm mit ungewohnlich veilfacher metastaticher Verbreitung, \'ii-Ii. ,'■■ \i h f. path. Anat., 1858, xiii, 271. f : ' ' M ' '\art: Ueber Diagnose der Zirbeldriisentumoren, Deutsch Ztschr. f. Nervenh., 1909, I i !l. uait: Wien. med. Wochschr., 1910, Ix, 505. 1 M Ir. i: r-;,,nniiMna k\stoniatosum hamorrhagicum der Glandula pinealis in Kombination mit .\l.(luliai-arkom, \i,.:,. \ : , li f. path. Anat., 1865, .vxxiii, 165. From: Intlaum; ,i : ,ivec reactions chromatique, fibrinese et leucocytique du liquide cephalo-rachidien. l.i. i Garrod, A. K, : I- ' i. 1., Path. Soc, London, 1899, i, 14. Gauderer, I.: /:i' ki^n iil, der Zirbeldriisentumoren (Teratoma glandula pinealis), Inaug. Dissert, Giessen, 1899. Gnldzeiher, U.: Ueber eine Zirbeldrusengeschwulst, Virchow's Arch. f. path. Anat., 1913, r.owers: Cases of Cerebral Tumors, Lancet, London, 1879. 394. Gutzeit. R.: Ein Teratom der Zirbeldruse, Inaug. Dissert, Konigsberg, 1896. Hart, C: Ein Fall von Angiosarkom der Glandula pinealis, Berl. klin. Wchnschr.. 1909, xlvi. 2298. Hedenius, I., and Henschen, F. : Tumor in Pineal Gland, Hygeia, Stockholm, 1913, Ixxv, 226. Hempel, K. : Ein Bcitrag zur Pathologie der Glandula pinealis. Inaug. Dissert. Leipzig, 1901. Heubner: Demonstration before the Versammlung deutscher Naturforscher und Aerzte, Diisel- dorf, 1898, M'.v uu ■] l - ntv, Ztz., 1899, Ixviii, 89. Hijiiiii !■ Ui and van Hasselt: Tumor glandul.T: pinealis, sive epiphysis cerebri, Xederl. 'IM.: ',, . ^k . 1913. i, 1271. . Hon.. .SI , I,, . ,, tile pineal gland II Clinical Observation, Archives of Internal Medicine. 'lidssiin, R. W: Tumor der Epiphysis cerebri. Munchen. med. Wchnschr., 1894. Howell: Tumors of the Pineal Body, Proc. Roy. Soc. Med., 1910, iii, 65. Hucter: Teratorum der Zirbeldruse, .Munchen, Med. Wchnschr.. 1913, 895. Joukovsky, V.: Hydrocephalie et tumcur congenitale de la glande pineale chez un iiouveau ne. Rev. mens. d. mal. de I'enf., 1901, xix, 197. Kny, E.: Fall von isolicrtem Tumor der Zirbeldriise, Neurol. Centralbl., 1889, viii, 281. Konig, E.: Ueber ein P^ammosarkom der Zirbeldruse, Inaug. Dissert, Munchen. 1894. Lawrence. IVV. P.: Tumor of Pineal Body, Tr. Path. Soc, London. 1899, 1. Lord, J. R..: The Pineal Gland; its Normal Structure; Some General Remarks on its Pathology: a Case of Syphilitic Enlargement, Tr. Path. Soc, London, 1899, 1. Marburg, O.: Zur Kenntniss der normalen und pathologischen Histologic der Zirbeldriise, Arb. a d. neuro Inst, pbersteiner, Wien. 1909, .xvii. 217; Die Adipositas Cerebralis, Wien. Med. Wchnschr.. 1908, Iviii, 2617; ibid, 1907, Iii. CAREY PRATT McCORD •Marburg, O,: Die Klinik der Zerbeldruse Krankunijen, Ergebn. d. inn. Med. u. Kinderl,.. 1913. "' '^Maclicll, H. T.: The Canadian Uncet. 1911, 171. "Report of two cases of sexual precocity." Massot- Note sur un cas de tumeur cerebrate avec polyurie, Lyon med., 187^. x. Mcstrezat, W. : Le liquide cenhalo-rachidicn. normal et patholopiqne. Pans 1912. Meyer A.: Adenoma oi the Pineal Gland, Jour. Nerv. and Ment. Dis., 1903. xxx, 216; .bul.. ''"''Mor'^je, Th.: A Case of Abnormal Physical and Sexual Pevelopment in an Infant of Two Years; Probably due to a Tumor of llu- Pum al (.land. Arch. Ped.at.. March 1913. 1. Mueller. K. : Ueber die P.crinlln. n,m ^1., Mcnstruat.on durcb ccrebrale Herdcikrankunnen. Neurol. Centralbl., 1905, 790. ., , „ , , ,• lu >, i lau v i Miinzcr A ■ Pubertas pra-cnx iiinl |i.\ , In-, h, hintwickelung, P.erl. klin. Wchnschr.. 1914, x, 1 Nassetti', F.- Contributo alio cono,,,,,,, ,1,1 lo.iiori ilella gl. pineali. Atti. d. r. Acad, d, hsiocnt '" ^N"ssettV"'F'^' Pineal cysts, Riv. sper. di freniat, ReggioEmilia, 1912 xxxviii, 291. Nemunmi, JL: Zur KenntAiss der Zirbeldnisengeschwulste, Monatschr. f. Psych.at. u. Neurol., ''"'■Neumann. P.: Ein neuer Fall von Teralom der Zirbeldriise, Inaug, Dissert. .Konigsberg, 1900. Niccolai. N.: Contributo clinico alio studio dclle sindromi epifisane e funztone endocrine, Riv. "'^' Nieden': "rail von "Tumor ('hydrops cysticu's) glandule pinealis, Centralbl. f. Nervenh. 1879. ii. '*'■ Nothnaeel- Topische Diagnostik der Gehirnkrankheiten. Berlin. 1879. 20fi. Nothnafel; GeschwClst der Vierhugel, Wiener med. Bl., 1888 162 193, 225 Oc^treich and Slawyk: Riesenwuchs und Zirbeldrusengeschwulst, Virchow s Arch. f. path. Ogle, C.*: ^Sarcoma of Pineal Body, Tr. Path. Soc, London. 1899 (two cases) Pappenhcimer: Ueber Geschwulste des Corpus pineale, Virchow's Arch. f. path. Anat.. 1910. '^'^' Pellizzi, G. B.: Riv. Ital. d. Neuropatol, etc., 1910, iii, 193; Lavorii d. 1st. d. Clin. d. Mai. Pirieales: Beziehunge'n der 'Aliromegalie zum Myxodcm, Samml. klin. Vortr.. New Series, 1899, "''■" Pontoppidan, K.: Ein Fall von Tumor der Zirbeldriise, Neurc Raymond and Claude: I,es tumeurs de la gland pmeale chez Reinhold, H.: Ein Fall von Tumor der Zirbeddruse, Inaug. Dissert. Leipzig, 1886. Rorschach, H, : Zur Pathologic und Operabihtkt der Tumoren der Zirbeldruse. Beitr. z. klin. ^'"'■'Russel, a'^^'e.'!' Cysts of the Pineal Body, Tr. Path. Soc, London, 1899, i, 15. Schearer: Enlargement of the Pineal Gland and Sclerosis of Brain in a Case of Chronic Epi- lepsy with Amentia and Aphasia, Edinburgh Med. Jour., 1875, xxi, 297. . Schmid, G.: Ueber latente Hirnherde, Virchow's Arch. f. path. Anat., 1893 cxxxiv 93. . Schmidt, P.: Beitrage Zur Diagnostik der Krankheiten des Gehirns, Med. Ztg., 1837, vi, 32. Schultz, R.: Tumor der Zirbeldrase, Neurol. Centralbl., 1886, 't39. , .. Segarey, A.: Les tumeurs de la glande pineale, Gaz. d. hop., Paris, 1914 Ixxxvu, 1141.1205, Simon, JC: Hemorrhagia de la gland pineale. Bull. Soc. Anat., Pans, 1859, xxxiv, 30i.. Stanley, S.: Dropsy of the Pineal Gland, Lancet, London, 1837, 935. ,.. , , ,„,, Thomas: Ueber riesenwuchsiihnliche Zustande in Kindesalte, Ztschr. f. Kinderh., 1912, v, Timme, W., and Bailey, P.: A Contribution to the Pathogenesis of Progressive Muscular Dyastrophy, with the Consideration of Evidence Connecting this Disease with Disturbances in Endo- crine Glands. (Abstract) Program 67th Annual Session Am. Med. Assn., 1916, 114. , Turner, F. Ch.: Spindle Cell Sarcoma of Pineal Body. Containing Glandular and Carcinoma- tous Structures. Tr. Path. Soc, London, 1885, xxxvi, 27. . „ , , \an der Heide, C. C: Tumor glandular pinealis sive epiphysis cerebri, Nederl. maandscher. v. verlosk. en vronwenz en v. kindernessk., Leiden, 1914, iii, 253-260. ^ , Verger. M.: Gliosarcoma develope an niveau de la glande pineale. Jour, de med. de Bordeaux, 1907, xxxvii, 216. Verger, M.: Teratom und Chorioephitheliom der Zirbeldruse, Verhaiidl. d. deutsch. path. Gesellsch., 1906, 58. Vikhodtseff, S. N.: Disease of Pineal Body with Involvement of the Eyes and Acromegaly, Vestnik Ophthalmol., Moskow, 1913. xx, 1014. Virchow, R.: Krankhafte Geschwulste, Berlin, 1863, i. , ^, Weed, L. H., and Gushing, H.: Studies on Cerebrospinal Fluid, viii, Amer. Jour, of Pliysi- ° "''^Weigertr'c.V' Zur Lehre von den Tumoren der Hirnanhiinge, Virchow's Arch. f. path. Anat.. 1875, Ixv, 212. Wcrnick, : Lehrbuch der Gehirnkrankheiten, 1883, iii, 299. WeisenburR, T. H.: Brain, 1910, xxxiii, 236. Wolf: Zirhcldriisenextrakt in der geburtsliilflchen Landpraxis, Deutsch. med. Wchnschr., 1913, xxxix, 1557. Zenner, A.: A Case of Tumor of the Pineal Gland, Alienist and Neurol.. 1892. xiii, 470. Ziegler: Lehrburch der patholovischen Anatomie, Ed. 4. 620. THE NUCLEAUS CARDIACUS NER\1 \'AGI AND THE THREE DISTINCT TYPES OF NERVE CELLS WHICH INNERVATE THE THREE DIFFERENT TYPES OF MUSCLE..* Edward F. Malonu Cincinnati. THREE FIGURES. When one lias carefully and critically studied in series of Nissl prep- arations the hrains of various mammals, there is revealed the presence of con.stant cell groups whose cells invariably possess certain definite charac- teristics as to size, form and structure. A separation of two groups of cells based merely upon dififerences in their histological characters is justified in the present state of our knowledge, only when such dififerences are constant and striking. When these conditions are fulfilled we may conclude that such constant and striking dififerences in cell character correspond to a difiference in cell activity, just as in other portions of the body. I have pointed out elsewhere that very real dififerences in cell character have been neglected by experimental workers, and that their results have been rendered thereby of less value. Since the dorsal motor (sympathetic) nucleus of the vagus is known to contain centers for the control of both heart muscle and smooth muscle, one would suppose that any real difiference in the cell character of various portions of this nucleus would at once claim the atten- tion of the experimental worker and that he would attempt to inform us as to the relation of these dififerent types of cells to the various functions of the vagus nerve. But such is not the case ; we are informed casually that some cells are large and others small, and thereafter the cells are consid- ered as if they were all of the same type. The discovery of two dififerent types of cells in the sympathetic vagus nucleus was not accidental ; I was led to look for this difiference on the following grounds. In the first place. I had recently shown that all cells concerned in transmitting efferent impulses to striated muscle possess a fundamental similarity of structure, whether the a.xone of the cell be in direct relation to the muscle or whether the cell act on the muscle through the mediation of one or more efiferent neurones. This observation naturally strengthened my belief in the significance of the relation of cell character to cell function. In the second place, I had observed the striking difiference between the cells supplying striated and those supplying smooth muscle. Since in a recent paper Molhant had shown that all fibers of the vagus supplying heart and smooth muscle arise from the sympathetic vagus nu- cleus, I concluded that in cells having such diverse functions there must exist a fundamental difiference in histological character. As was anticipated, two different types of cells were found ; the evidence in favor of ascribing to the cells of one type the innervation of heart muscle, and on the other EDWARD P. MALONE hand, to cells of the other type the innervation of smooth muscle, will be considered later. The material available consisted of two complete series. The first was a series of the brain of a lemur, while the second was of the brain of macacus rhesus. Both brains were fixed in 95 per cent, alcohol, and after the usual treatment with absolute and chloroform, were imbedded in par- affin. Serial sections were stained in a 1 per cent, aqueous solution of toluidin blue (Griibler), differentiated in 95 per cent, alcohol, dehydrated in absolute, cleared in xylol, and mounted in Canada balsam. Series of brains of other forms will have to be prepared and studied before I feel justified in committing myself upon many points, and the present article has therefore been limited, especially as to the exact location and distribu- tion of the dilferent types of cells. 'J'he efiferent fibers of the vagus nerve arise from two distinct columns of cells. From the nucleus ambiguous arise the fibers which supply striated muscle, while from the so-called dorsal motor nucleus arise fibers which innervate heart muscle and smooth muscle. This fundamental difference as to function, which has been proved beyond doubt by the recent investiga- tion of Molhant, had not been clearly recognized ; this obscurity was prob- ably favored by the fact that the nucleus ambiguous, together with the motor nuclei of the eleventh, seventh and fifth cranial nerves have often been regraded as visceral, regardless of the fact that their cells cannot be distinguished either histologically or functionally from the cells of the other motor nerves supplying striated muscle. Thus this classification giv- ing undue emphasis to a condition which in mammals no longer exists, has contributed to the general lack of appreciation that the dorsal motor nucleus of the vagus is composed of cells which ditifer radically both histologically and functionally from those of the nuclei supi)lying striated muscle, regard- less of whether the striated muscle be of somatic or of visceral origin. The name "dorsal motor nucleus" does not indicate the true function of this cell group, and I shall use the name "sympathetic or visceral luicleus of iht vagus." The location and extent of the .sympathetic nucleus of the vagus is well known and will not be considered in this paper, except to call attention to the fact that it extends as a long column of cells dorso-lateral to the hy]io- , glossus nucleus from the lowest portion of the medulla to almost the level of the oral i)ole of the inferior olive. An excellent description of the loca- tion of this nucleus is given in Jacobsohn's monograph. The oral portion of the nucleus is composed of small cells of the type shown in figure 2; this is true both in the ca.se of the lemur and the monkey. As one follows the nucleus caudally a second type of cell begins to appear (Fig. 1). The portion of the nucleus in which both types of cells occur is at the level of the oral portion of the hypoglossus nucleus, and here the sympathetic nucleus attains its greatest diameter. The cells of each type are partly .separated from each other, although no sharp line of separation is evident. In the Page „";.'■ KANSOHOff MEMORIAL VOLUME lemur the large cells (Fig. 1) form a fairly compact group dorsal from the small cells, whereas in the monkey their relative position is reversed. Proceeding further in a caudal direction, the small cells become rapidly less numerous and finally disappear. After the disappearance of the small cells the sympathetic nucleus, consisting now entirely of the large cells (Fig. 1) proceeds caudally as a well developed and definite group. In the most caudal portion of the medulla the sympathetic nucleus is much reduced ; only a few cells are seen in each section, and these cells become smaller and have the appearance of the smallest cell in figure 1 ; in this portion of the nucleus (the caudal end) are probably also cells of the type shown in figure 2, that is, similar to those in the oral portion of the nucleus, but at present I cannot be absolutely sure of this, as the surrounding cell groups have not been sufficiently studied. The smallest cell shown in figure 1 is probably a transition type between the other cells of figure 1, and those of figure Z. To sum up, the sympathetic vagus nucleus consists of three portions : (a) an oral portion whose cells are of the type in figure 2; (b) a middle portion whose cells are shown in figure I ; and (c) a caudal portion composed of cells shown in figure 2 (same as oral portion) and also of cells such as the smallest cell in figure 1 (probably a transition type). It is not my intention to present in this paper a detailed description ol the types of cells in the vagus symjiathetic nucleus, but rather to point out the fact that there are very definite differences in histological character between the cells of the various groups ; a study of the illustrations will make this evident. Since these differences in cell character exist, and since such differences must necessarily be an indication of corresponding differ- ences of cell activity, we may now consider whether these different cell groups of diflferent character may be brought into relation with definite functions. In the first place, it, has been shown by Molhant, in his excel- lent and extensive work on the vagus nerve, that the sympathetic nucleus of the vagus gives origin to all the fibers of the vagus which supply smooth and heart muscle, and that all its cells give origin to such fibers. Further, he has shown that the oral portion supplies smooth muscle (stomach, lungs), the function of the extreme caudal portion is doubtful (possibly connected with the trachea and bronchi), while the intermediate portion supplies heart muscle, but he has failed to connect these different functions with different types of cells. Concerning the function of the caudal portion of the nucleus, which is composed of cells of the type shown in figure 2, together with cells resembling the smallest cell of figure 1, we can draw no definite conclusion. The oral portion consists exclusively of the type of cells .shown in figure 2, and we may conclude that this type of cell supplies smooth muscle ; of course this does not justify us in concluding that this type of cell (Fig. 2) is the only type of cell which may supply smooth muscle, or that this type may not in other regions have a different function. Overlapping the cells supplying smooth muscle (Fig. 2) and extending caudally unaccompanied by other types of cells is the type of cell shown in figure 1. and this portion EDWARD F. MALONE of the S)'nipathetic nucleus lias been shown (Molhant) to supply heart muscle. It is evident therefore that the cells of figure 1 supply heart muscle, while those of figure 2 supply smooth muscle (stomach and lungs). In addition there is purely histological evidence to support the functional rela- tions of these two types of cells (Figs. 1 and 2), since the cells supplying heart muscle (Fig. 1) are a type intermediate in histological structure bc- tiveen those supplying smooth muscle (Fig. 2) and those supplying striated muscle (cells of hypoglossus nucleus, Fig. 3). The relative size of the Nissl bodies in the three types of motor cells illustrated in figures 1 to 3 is especially worthy of notice. The fact that nerve cells supplying heart muscle are of a type intermediate between those supplying striated and smooth muscle constitutes one of the strongest arguments in support of the importance of the relation of cell character to cell function, since heart muscle is histologically intermediate between the two other types of muscle. The cell group which supplies heart muscle, composed of the character- istic cells shown in figure 1, I shall name provisionally "nucleus cardiacus nervi vagi." I do not feel justified in assigning any name to the other por- tions of the vagus sympathetic nucleus, but shall be content with pointing out that the cells of the oral portion which supply smooth muscle are of a definite type (Fig. 2). A further division is at present not advisable be- cause the functional relations of the caudal group are not understood, and because the pigmented cells described by Jacobsohn in man, have not been identified and studied (of course, in lower animals pigment is wanting, although homologous non-pigmented cells may e.xist). Further subdivision of the sympathetic nucleus, together with a detailed description of the loca- tion and extent of the various cell types, the consideration of transition types, and of the relations of the nucleus to the cells of surrounding nuclei, must await a thorough study of numerous series of various aninnls (includ- ing man). CONCLUSIONS. 1. The histological character of a nerve cell is an indication of its func- tion. Dififerences in connections with portions of the organism which differ merely in spatial relations do not involve a difTerence in the character of the nerve cells, but are associated merely with the location of the nerve cell; for instance, arm and leg muscles, flexors and extensors are all inner- vated by the same type of cell, although such dififerences in peripheral con- nections correspond to differences in the position of the corresponding nerve cells. * 2. The three types of muscle are innervated by three distinct type of nerve cell, which, however, are related to one another in such a manner that the cell innervating heart muscle is of a type intermediate between the other two types of cells. Heart muscle, smooth muscle, and striated muscle are innervated by cells such as are illustrated in figures 1, 2 and 3 respec- RA.YSOHOFF MEMORIAL VOLUME NUCLEUS CARDIACUS NERVI VAGI KinvARii F. Malonr Explanation of Figures. 1 to .1 Tile ceHs illustrated in the three figures were all drawn from the same section witli the aid of the camera lucida. and for all cells the magnilication is 580 diameters. 1 have attempted to reproduce as nearly as possible the actual appearance of the cells, combining to a certain extent ditTerent levels of focus. These three figures clearly show that the cells supplying heart muscle (Fig. 1) are histologically intermediate between the cells supplying smooth muscle (Fig. 2) and those supplying striated muscle (Fig. 3). 1. Cells from nucleus cardiacus nervi vagi of lemur. The smallest cell represents probably a transition type to the cell type of figure 2, and this type occurs more fre- quently in the caudal portion of the vagus sympathetic nucleus where it is found together with the cells of the type shown is figure 2. 580 diameters. 2. Cells of vagus sympathetic nucleus of lemur which innervate smooth muscle. In the oral portion of the sympathetic vagus nucleus these cells occur alone; more caudally they oceur i.if^ttlur with the cells of the nucleus cardiacus (Fig. 1) in the most oral portion <H*.,^ju. muscle within the spleen. The second contraction is passive, and is due to the profound fall in blood jiressure. and perhaps, somewhat to the asphyxia which followed the injection of the benzyl benzoate. Artificial respiration was started at "1" and stopped at "2." Although the blood pressure again returned to a high tension (continued action of the barium) and the spleen tracing also marked a low level (also barium contraction), still there is no evidence that the benzyl benzoate exercised any relaxing action on the spleen. although the dosage was perhaps sufificient to have killed the animal if arti- ficial respiration had not been given. Under artificial respiration animals can withstand very nuich larger doses of the drug without dying, than is possible under natural respiration. This indicates that the animals do not Page 3Si EDWARD C. MASON AND CARL E. PIECK die of thrombosis as might be suspected from the rather unsatisfactory character of the drug for intravenous injection. The final recovery of the heart and circulation, if artificial respiration be maintained, shows that no permanent thrombi are lodged in any vitally important vascular areas. Fig. 6 shows the respiration, kidney volume (oncometer) and blood pres- sure. In the beginning 4 cc. of benzyl benzoate solution was injected. Slight eiTects were produced in all three tracings. The small shrinkage in kidney volume is obviously secondary, and due to the fall in blood pressure. If the arterioles themselves in the kidney had dilated the volume record would have risen, as occurs after the constriction produced by the 1 cc. injection of adrenalin (at the center of the tracing) begins to wear off. The shrinkage of the kidney volume after the adrenaline is active and is due tO' the adrena- line stimulating the myoneural junctions of the vasoconstrictor nerves in the renal arterioles. Following the adrenaline a further dose of 7 cc. of benzyl benzoate was given. The results of this were exactly analogous to those produced by the 4 cc, but were correspondingly more pronoimced. RANSOHOFF MEMORIAL VOLUME 11ie recently suggested use of benzyl benzoate in clinical conditions pre- sumably dependent" on excessive or abnormal contraction of the uterus^ indicated that the drug would probably produce relaxation of this organ. Figs 7 and 8 show the results we have obtained in the study of the action of the .Irucr on this organ. In Fig. 7 an injection of 3 cc. was made and produced verv obvious results on the respiration and blood pressure. On the uterus, howe;er, the results are very slight. Fig. 8 also shows the effects of an injection of 5 cc. of the drug. This dosage finally stopped the uterine contractions, but not until the animal had died. Obviously one could not such large aiiK of the drug. This dosage hnally stopped tne urerine until the animal had died. Obviously one could not nts clinicallv. In these tracings the uterus remained EDWARD C. MASON AND CARL E. PIECK RANSOM OFF MEMORIAL VOLUME in situ and great care was used not to disturb its innervation or blood supply, and to keep the organ warm and moist by closing the abdominal wall and covering the recording apparatus with the intestines (see Jour. Lab. and Clin. Med.. 1917, iii, 63). In regard to these two records, however, it should Figure be stated that it is often difficult to secure entirely satisfactory tracings of the uterus in situ in dogs, and we should not be inclined to lay too great em- phasis on these observations without checking the results by a considerable number of experiments on animals of ditTerent species, which we have not EDWARD C. MASON AND CARL E. FIECK as yet had an opportunity to do. In our present experiments the uterus had previously been roused to increased activity by the injection of pituitrin. One of the most important cHnical uses suggested for benzyl benzoate is in the treatment of bronchial asthma.* Fig. 9 represents two tracing taken from separate dogs and mounted together. They show the action in spinal dogs of histamine (B-iminazolylethylamine, "ergamine"). benzyl benzoate, codeine and adrenaline on the bronchioles as recorded by a special aspira- tion method (see Jour. Pharmacol, and Exper. Therap., 1914, vi, 57; also, Jackson's Experimental Pharmacology, C. V. Mosby Co., 1917. St. Louis, p. 287). In these tracings (also Figs. 10 and 11) a shortening of the ampli- tude of the lung record means contraction of the bronchioles, and increase in the amplitude of the lung tracing shows dilatation of the bronchioles. In Fig. 9 the left hand record shows a contraction of the bronchioles produced by the intravenous injection of two-thirds milligram of ergamine. This led to a bronchial contraction which 10 cc. and, later 30 cc. of an aqueous solu- tion of benzyl benzoate did not relax. An injection of adrenaline (2 cc.) Page 3S7 RASSOHOFF MEMORIAL VO LUME produced prompt bronchial dilatation. In the right hand tracing codeine was used to produce the initial bronchial contraction and then 3 cc. of the 20 per cent benzoate made up in 75 per cent, alcohol was injected mtravenously. The dog weighed 8 kilos and it would appear that this dosage should cer- tainly have caused dilatation of the bronchioles. This did not occur, how- ever and as a further check on the technic of the experiment 2 cc. of adrena- EDWARD C. MASON AND CARL E. PIECK lin was injected. A bronchial dilatation followed although the heart stopped beating (from the eflfects of the codeine and benzyl benzoate). Fig. 10 shows that 2 cc. of pure benzyl benzoate (made by the Harmer Laborator- ies) did not produce the slightest indication of a bronchial dilatation follow- ing a contraction produced by "ergamine." Adrenaline, however, caused a marked dilatation. This seems to indicate definitely that benzyl benzoate does not cause a bronchodilatation in intact (pithed) dogs under the condi- tions obtaining in such experiments as we have here carried out. Fig. 11 shows three separate tracings mounted together. From the legends it will be seen that benzyl benzoate did not produce satisfactory bronchodilatation in either instance. The possibility that benzyl benzoate might be used clinically in pulmonary hemorrhage in cases of tuberculosis led us to investigate the action of the drug on the pulmonary blood pressure. The method we have used for re- cording the pulmonary arterial pressure is indicated in Fig. 12. (See Jour. Lab. and Clin. Med., 1920, vi, 1). In the diagram it will be seen that a cannula tied into the left pulmonary artery connects with a water mano- meter, the distal end of which is joined to the lower end of a burette. The manometer and tubes to the artery (and the cannula) are filled with normal salt solution. The upper end of the burette is connected with a recording tambour which writes on the drum. The tambour, the upper part of the burette and the connecting tubes are filled with air. By this method the pulmonary blood pressure record represents a magnification about 150 times greater than would be recorded by a mercury manometer. The varia- tions in the pulmonary tracings should, therefore, be reduced about 150 times in amplitude in order to compare them directly with the associated carotid tracings which, in our records, were made with a mercury manometer. Fig. 13 shows the results we have observed on the pulmonary arterial pressure. Near the beginning of the tracing 3 cc. of benzyl benzoate was injected and a typical, prolonged fall in the carotid pressure was obtained. In the pul- monary pressure, however, there was produced at first a sharp temporary rise which was succeeded by a few gasping movements. But on the average there was extremely little variation in the pulmonary pressure, either in the way of a rise or a fall. Later a 3 cc. injection of benzyl benzoate was given again. The fall produced in the carotid pressure was again quite typical, but the pulmonary pressure showed only a very slight, transient rise. A small injection of adrenaline was finally given in order to check up the accuracy of the technic in the experiment. Fig. 14 shows two short pul- monary tracing (mounted together). Here again the drug produced only the slightest changes in the pulmonary pressure. In studying these tracings one must, of course, constantly bear in mind the greatly increased magnifi- cation of the pulmonary over the carotid records. It is obvious that if the drug should act in clinical cases in a manner at all analogous to that in RA NSOHOFF MEMORIAL VOLUME which it lias behaved under these experimental conditions, it could be of no use in the matter of treatment of hemoptysis in puhnonary tuberculosis. REFERENCES. 1. Maclit, David I.: Jour, Pharmacol, and Exper. Thcrap., 19IS. xi, No. 6, p. 421. 2. Macht, David I.: Jour. Am. Med. Assn., August 23, 1919, pp. 599-601. 3. Litzenhpre. Jennings C: Jour. Am. Med. Assn.. August 2.3, 1919, pp. 6C1-603. 4. Macht. David J.: .Southern Med. Jour., July, 1919, xii. No. 7, p. 367. RELATION OF THE DEVELOPMENT OF THE GASTRO- * INTESTINAL TRACT TO ABDOMINAL SURGERY.* W. J. Mavo, M. D. Rochester, Minn. THE RELATION OF ANATOMY TO PRESENT DAY SURGERY. The late Corydon L. Ford, professor of anatomy at the University of Michigan Medical School, was justly considered the greatest teacher of anat- omy of his time. I well remember the three years in which I studied anat- omy under him, and the impression he made on the students by his clear and forceful presentation of this ordinarily dry subject. He was then a man past middle life; he wore a beard, shaved the upper lip, and because of a congenital clubfoot he walked with a decided limp by the aid of an ivory- headed cane. I speak of these physical factors because they were part and parcel of the man in relation to his teaching. He presented anatomy not alone as a fundamental science which it was necessary to master for the purpose of laying a foundation for clinical medicine, but as a living thing to be considered in almost every professional act. He was closely in touch with the clinical issues of his time, and with anatomy he taught most valuable lessons in physiology and pathology, so that the student gained knowledge of his subject in its relation to his work. The university courses in surgical anatomy were excellent, yet Ford taught us more surgical anatomy than we learned in these special courses, and he also taught us medical anatomy, in order that we might see the patient from the anatomic standpoint, and recognize pathologic deviations from the normal in the early stages. We were drilled in the use of Holden's "Anatomical Landmarks"; I have spent many hours with this little book, going over the living body that I might learn the relation of the external to the internal. As volunteer assistant I had the further privilege of demonstrating anat- omy at the University of Michigan, and the fascination for anatomic detail in relation to medicine and surgery has remained with me. My seat com- panion was the late Franklin P. Mall, afterward professor of anatomy at Johns Hopkins, and the most distinguished anatomist of his time. Mall was a choice spirit, an anatomist of the research type. On one occasion in show- ing me the manner in which the heart, by its peculiar twisting contraction, empties all the blood from its cavities as one would wring a cloth, he re- marked that a cavity like the bladder cannot empty itself to the last drop by contractions alone. He said that anatomy since Ford's time had dealt too much with abstract matter. Mall's observation has an important bearing on catheter cystitis, an infection of a small amount of residual urine in an overstretched organ. •Mayo Foundation lecture, given before tlie University of Medicine and tlie Physicians' and Surgeons' Club, Rochester, Minn. Journal of the American Medical Association. February. 1920. RANSOHOFF MFMORIAL VOLUME During my active experience in surgery, working with many different assistants. I have not always been impressed with their knowledge of anat- omy, although all have possessed a fair knowledge of pathology. At times it would seem that they were more familiar with minute pathology than with anatomy. Microscopic histology and pathology, while not overdone, have been allowed to overshadow anatomy and gross pathology — these the surgeon or internist must see with his own eyes if he is to do his best work. It is a question in my mind whether, generally speaking, anatomy is as well taught today as it was in my student days ; whether it is taught with a view of instilling in a man a love for the subject, or merely as a foundation for medical practice. I believe this tendency is correctly interpreted by teaching anatomists of the type of Jackson and others, who are taking steps to remedy the existing defects by the better balancing of anatomic teaching. This is also true of the teaching of present day pathologists. In surgery of the abdomen especially, a wide knowledge of embryology and anatomy is essential. In the olden time when operations were done in late periods of pathologic conditions, and were destructive rather than reconstructive because it was necessary to save life and it was too late to save function, one could fully appreciate the answer of the distinguished surgeon who originated excision of the hip when asked concerning the ana- tomic details of the operation: "Damn the anatomy; stick close to the bone." Today the bulk of surgery is not done for gross defects but for pathologic conditions which have not deviated from the normal to such an extent that destructive surgery is necessary, but are still in condition for reconstruction. It has been said that the anatomist never made a good sur- geon : that it was the pathologist who made the surgeon. This is true only of the vanishing German type. The surgeon of tomorrow must follow in the footsteps of such men as Deaver ; he must be an anatomist and a physi- ologist, and living pathology must hold a greater place in his mind than the pathology which has been developed from the mortuary and has dominated medicine for the past generation. For many years I have been interested in elucidating problems of sur- gery of the abdomen. Clinical diagnosis has been notoriously unreliable, and the postmortem does not show the chronic disease from which the patient was sick during life, but rather the particular complication from which he died. Always, when I have faced a new problem in this field. I have gone back to embryology, anatomy and physiolog>' in order to gain an idea of the meanings of those pathologic deviations which we are called on to treat. It may not be out of place at this time to outline sketchily some of the anatomic and physiologic principles that have grown up with the surgery of the abdomen, and on which depends the explanation of many phenomena that could not otherwise be understood. From the time the food passes through the pharynx until it enters the rectum we have comparatively little control over it. Some control is exer- cised in the esophagus and even in the fundus of the stomach so that by IV. J. MAYO initiating retrograde movements, retching, and so forth, some food may be ejected. The same is true in the sigmoid ; but even in it the control at best is but partial and indirect. The biologists have pointed out that the theory of the three blastodermic membranes is a working rule and not a law, having many exceptions ; but at least it leads to logical thought. To a certain extent this is also true of the idea of the derivation of the gastro- intestinal tract from the fore, middle and hind guts. Yet these primitive derivatives, while not as exact in the present day human body as might be desirable from a purely scientific point of view, have great value as outlines for the student. From the foregut come the stomach, the duodenum down to the com- mon duct, the liver and the pancreas, all organs which prepare food for digestion but do not themselves absorb. The stomach does not absorb even water, although it will take up certain chemicals and poisons, alcohol, for instance. The derivatives of the hindgut likewise absorb nothing except certain chemical substances, and rectal feeding, as spoken of in its ordinary sense, does not exist : it is simply a means whereby material placed in the rectum is quickly carried by what Bond calls "mucous currents" back into the derivatives of the midgut for absorption. The so-called colon tube passes out of sight through the anus, coiling in the rectum, and but seldom passes the rectosigmoid barrier. The derivatives of the foregut have their blood supply from the celiac axis. The derivatives of the midgut, in which absorption takes place, are supplied from the superior mesenteric artery, while the inferior mesenteric artery supplies the derivatives of the hindgut as far down as the rectum, and very largely the rectum also, although the rectum and anal canal obtain a small supply from the middle and external hemorrhoidals because of their origin from the cloaca and the protodeum. Rosenow's work on the specificity of bacteria shows the bacteria that have been cultivated in certain soils, in the gallbladder, for example, when placed in the circulation, are peculiarly attracted to the organ to which they have been acclimated. That is, strains of bacteria derived experimentally from a gallbladder will more often set up a cholecystitis than if they were derived from some other organ. This is true along so many lines connected with the vascular system that we must admit at least the possibility that the blood supply is to a certain extent specific and that organs exercise some peculiar chemotaxis which physiologically and pathologically directs cer- tain substances of the blood content to them. How else can we explain the rapidity with which phenolsulphonephthalein is eliminated through the kid- neys? And recent work in physics suggests that the attraction may be a physico-chemical one. Very delicate instruments appear to show that each organ has its own electrical reactions and polarity, suggesting that cancerous growths can be recognized in this way. Embryologically the first portion of the duodenum ends, not at the py- lorus but at the common duct, and the duodenum above the common duct embryologically is a part of the stomach and a vestibule to the small intes- RANSOHOFF MEMORIAL VOLUME tine; like the stomach and other acid-containing organs, it is extremely liable to ulceration. Ulcers of the duodenum occur more commonly in men than in women, possibly because the first portion of the duodenum in women is more nearly horizontal, naturally permitting of a higher alkaline level for the bile and pancreatic juice, and thereby reducing the liability to ulcera- tion. In animals with bilocular stomachs the division between the two stomachs is at the incisura of the human stomach, and the physiologic activity of the pyloric half of the stomach, especially at the incisura, is quite evident on roentgen-ray examination, although the musculature composing the primitive sphincter has disappeared. The termination of the absorbing intestinal area in the transverse colon near the splenic flexure embryologically marks the end of the absorbing area. It is interesting to note that, although the proximal half of the large intestine has no marked anatomic differences from the left half, in the embryo villi are to be found in the right half which are similar to the villi of the small intestine, although they disappear as development proceeds. An observer, watching with the roentgen ray the churning back and forth in the head of the colon sees that the greater part of this activity is proximal to the loca- tion of the cecocolic sphincter which exists in the ascending colon of some of the lower animals, and that physiologic contractions are most marked in this situation. Retardation of the passage of food through the intestinal tract has its origin in embryologic physiology. Muscular control by means of sphincters, delay by means of the valvulae conniventes which also pre- sent larger exposed surfaces for absorption, delay by sacculations, as in the large intestine, and mechanical delays, such as the high attachments of the splenic flexure which necessitate muscular activity in order to pass the food refuse into the nonabsorbing part of the large intestine and render the descending colon physiologically empty, are examples. The rectosigmoid is a most remarkable mechanical device for retardation of food end-prod- ucts. Since nature is most sparing of waste, even of water, in the terminal half of the large intestine, especially the sigmoid, the fluids are gradually squeezed out of the refuse and passed by reverse currents back into the proximal half of the colon for absorption. Rotation has great surgical significance. In the embryo and in many lower animals throughout life the stomach hangs with its lesser curvature facing ventrally; and embryologically the lesser curvature is the anterior wall of the stomach. Rotation turns the stomach and pancreas on their right sides. The pancreas, embrylogically an intraperitoneal organ, loses its posterior layer of peritoneum, which becomes fused behind with the fascia. This explains why, in the type of acute pancreatitis and fat necro- sis which might be picturesquely called "perforation," the pancreas may involve the fat behind the peritoneum as well as the intra-abdominal fat; why occasionally, in traumatism, pancreatic secretions escaping into the lesser cavity of the peritoneum may penetrate into the omentum and form a collection of fluid in what is known as the omental bursa, reopening the Page S9^ W. J. MAYO cavity which in fetal life exists between the layers of the omentum before tliey are fused as high as the transverse colon. The position of the duodenum is altered by rotation and its third portion becomes retroperitoneal, a fact of great importance in connection with operations on the right kidney. Unless care is exercised in performing a nephrectomy in cases in which there is chronic inflammation around the pelvis, and especially in malignant disease, the duodenum may be injured, and immediately or a few days later a fistula form from which the patient may die unless it is repaired anteriorly by a transperitoneal operation. Very scanty mention of this accident is found in the literature, but I have reported several cases of this character. Unless careful dissection is made, this retroperitoneal portion of the duodenum also may be injured in the removal of cancers of the ascending colon. Rotation as it affects the intestinal tract is also of great surgical impor- tance. The large intestine, having its origin on the left side of the body, passes to the right and does not reach its normal situation until after birth. The late peritoneal attachments are often described as veils or adhesions, and are given unwarranted credit for causing trouble. Failure of rotation or partial rotation will cause the physical signs of an appendicitis to appear at whatever point the rotation of the head of the colon is interrupted. The attachments of the large intestine to the right side are not only late and less close than those on the left, but also, since the cubic capacity of the right lower thorax is less than that of the left lower thorax, because of the liver, the right kidney normally lies lower than the left. The nephrocolic liga- ment may be called on to bear much of the weight of the head of the imper- fectly attached colon which acts like the car attached to a balloon, and may, by traction, drag the kidney down. We think of the large intestine as having a short mesentery ; but as a matter of fact, it has a very long mesentery on the inner side, which is the only side of importance, as the blood vessels, lymphatics and nerve supply are always to be found in the inner long leaf which follows the colon during its migration. The outer peritoneal attach- ments which hold the colon in place laterally may, therefore, be divided with- out encountering any structures of importance, and the large intestine, on its long inner leaf of mesentery, can be drawn out of the body for easy manipulation and operation. There is one exception; that is, the attach- ments of the splenic flexure are derived from the omentum and contain a blood vessel which must be tied. Some years ago I called attention to this method of mobilizing the large intestine, which is based on these anatomic facts and very greatly aids in operations on the colon. The small intestine, originating in six primary convolutions on the right side, has its mesenteric attachment from left to right, from above down- ward, passing behind the umbilicus. This is the reason why in obstructive and other disturbances of the small intestine, unless localized by involve- ment of the peritoneum, the pain is referred to the vicinity of the umbilicus, although the cause of the pain may be in a loop of intestine at a distance. Page 39$ RANSOHOFF MEMORIAL VOLUME In picking up a loop of small intestine, it is sometimes difficult to determine which direction is up and which is down. Monks, in a beautiful piece of work, has shown how this can be done with facility. If a loop of intestine drawn out of an abdominal incision is held by an assistant, and the surgeon, grasping the intestine with the fingers on one side and with the tliumb on the other, passes down to the bottom of the mesentery, and finds that his fingers and thumb still grasp the root of the mesentery as started above, the direction is up and down ; but if the position is reversed at the base, then the direction is the opposite. In picking up a piece of small intestine one should be able to recognize the part of the bowel from its appearance. The upper jejunum is thick and wide, the mesentery is thin, and the vessels are large, long and straight, having but one or two primary arcades close to the base. In the lower ileum the intestine is thin and the mesentery thick, the fat some- times following the vessels a little way up along the intestinal wall. The vessels are smaller, shorter, and there are a number of arcades, sometimes two, three or four, in the adjacent mesentery. Attention to these details makes ready differentiation possible. The study of the peritoneum is profitable to the surgeon. The resistance of the peritoneum to infection is an inherited faculty. The meninges and pleura have less resistance. In the earthworm (common angleworm), the food, in its jirogress through the primitive gastro-intestinal canal, is admitted into the coelom, or body cavity, which is the forerunner of the peritoneum, for direct absorption. The contaminated peritoneum liefore infection takes place usually needs no drainage after mechanical cleansing; drainage often does harm rather than good. The slowly acquired special resistance of the pelvic peritoneum of women to infections in the course of countless genera- tions of sulTfering from puerperal and other infections, is well known; and the mortality rate of operations involving the pelvic peritoneum, such as resections of the rectum for cancer, is much less in women than in men. Let me repeat that the teaching of anatomy, as related to constructive surgery rather than to the destructive surgery of the past, should be based on the needs of the surgeon of today, to enable him to cope with the diseases of today. If I were to write a book (I have no intention of inflicting one on the medical public), I should take up the fascinating story of embryology, anatomy and ])hysiology in relation to the work of the surgeon of tomorrow, the story of the anatomy of the living to enable us to treat the i)athology of the living during the early stage of deviation from the normal physiologic state. CO-ORI^IXATIO\ OF THE FUN'CTIOXS OF THE OASTRO-IXTESTIN'.AL TR.^CT The two most primitive functions of a living body are maintenance of nutrition and reproduction, and nature has thrown about these functions the greatest possible number of safeguards. First, the body must be nourished, and second, new life is to be brought into being. This is as true of the Page aim W. J. MAYO simple cell as of the most complex organism. The more ancient the organ, the greater its resistance. The small intestine has an enormous resistance to disease and seldom is the seat of neoplasm. The testicle, which is the primitive rei)rodnctive organ, has a long heredity and freedom from disease. On the contrary, the ovary, which is descended from the testicle, is. like other less ancient organs, such as the stomach, the rectum and the large intestine, a frequent seat of neoplasm. Methods of ciMitrol over the visceral functions were established before man had a central nervous system; the.se controls are still independent of it. It might even be surmised that the attempt of the central nervous system to gain control over visceral and other functions previously established may have to do with neurasthenia, especially its visceral manifestations. Starling well says that those internal secretions, which he calls hormones, precede all types of nervous systems in visceral control. One is perhaps justified in looking on the sympathetic as the more primitive nervous system and in be- lieving that the means whereby the central nervous system is attempting to gain this control over the vegetative functions is through the autonomic nervous system. The liver, entirely separated from all its connections, can be made to secrete bile, and the kidney similarly to secrete urine. For that matter, the entire viscera have been completely separated experimentally from the nerv- ous system and even lifted out of the body, and by appropriate mechanical connections made to live and function for some hours. The central nervous system, we find, has more or less control of those organs which have been added more recently, especially organs of convenience, such as the fundus of the stomach, into which a quantity of food may be placed rapidly for elabo- ration, as the magazine of a coal stove may be filled. The sigmoid and the bladder also have temporary storage function ; but in other resjjects the cen- tral nervous system, bevond initiating action, plavs a small ]3art in \'egetative life. The growth of the central nervous svstem in relation to the organs of special sense is interesting. First, the sense of taste, which made the selec- tion of food possible ; second, the sense of smell, which enabled the primi- tive stoma to be turned toward food, and third, the sense of hearing, which was placed in the middle of the head because danger threatens from behind as well as in front. The sense of sight came during the rapid development of all the higher cerebral faculties, and direct pathways were established between the eye and all parts of the brain, so that the sense of sight over- shadows in importance the other special senses. Even memory in most persons has its basis in visual phenomena. The relatively short heredity of the central nervous .system accounts for its instability. It is interesting to note that the sympathetic nervous system is in close relation with the endocrine glands, and that the importance of the internal secretion of an organ may be estimated by the closeness of its relation to RANSOM OFF MEMORIAL VOLUME the sympathetic system. The pituitary, one-half sympathetic and one-half gland, the suprarenal, with its similar association, and the thyroid, are ex- amples; the spleen has no internal secretion of great importance, and only small connection with the s_\anpathetic system. Still another form of control is found in the primitive character of the nonstriated muscle. These fibers have the power of originating motion independent of a known nervous system. A little piece of the wall of the small intestine will contract for hours when placed in Locke's solution and properly stinnilated. Many visceral functions are dependent on the non- striated muscle. We are indebted to Keith for revelations with regard to the curious nodal system which acts to collect the impulses that have their origin in the primitive fibers of the nonstriated muscle. This has been most carefully studied with reference to the heart. The heart-beat starts in the sinu-auricular node, is diffused through the auricular musculature, and is passed by the muscle-band of His to the vetricles, timing the ventricular beat. Keith's nodes are composed of a curious type of primitive muscle- cell with some fine fibers from the autonomic nervous system which evi- dently were added later. These nodes are in eflfect the controlling ganglions of the action of the nonstriated muscle in organs. Keith has pointed out the situation of eight nodes, four located and four not fully identified, througli which control is maintained. When food passes through the pharynx, all direct control is at once lost, and here is situated the first node. The cardia is a true sphincter and normally is closed. The food passing through the esophagus arouses contractions in the nonstriated muscle of the esophagus ; these impulses are carried to the second node, which relaxes the cardiac orifice. Failure to relax the cardiac orifice results in that curi- ous condition called cardiospasm from which many persons suffer and starve for years, and often die from obstruction sujiposed to be due to can- cer. If we have knowledge of the nature of the diseasf. cure is easy ;ind certain. The third node is not at the pylorus as one wduld think, but at the termination of the primitive foregut near the common duct. It is in- teresting to note that, as pointed out by Ochsner, there are remnants of a prehistoric sphincter at this point. Disturbances of this node produce the condition called pylorospasm, which accounts for many gastric disturbances masquerading under dififerent names. This node is also concerned in chronic gastric atony and some of the phases of acute dilatation of the stomach. The fourth node is near the duodenojejunal juncture and is con- cerned normally in peristalsis and in segmentation or pendulum movements of the small intestine, and abnormally in producing gastromesenteric ileus. The fifth node is at the ileocecal juncture and is concerned with many of those phenomena about which Lane has written so interestingly under the general head of ileac stasis. The sixth node is near the middle of the trans- verse colon, and through its control of antiperistalsis prolongs the reten- tion of food products for absorption in the right half of the colon. The Page S9i W. J. MAYO seventh node is in the rectosigmoid region, and disturbances in the function of this node are probably responsible for the giant colon of Hirschsprung's disease. The last, or eighth, node is concerned with rectal control. It ma\' be said that wherever nonstriated muscle exists, the power of originating contraction exists. The intestine, like the heart, has two beats. The first, called the peristalsis, beats once or twice to the minute. The second, as pointed out by Mall, is the heart of the portal circulation and beats from eighteen to twenty times a minute, forcing the blood to the liver. In the pregnant uterus, the beat of the nonstriated muscle is recog- nized as the uterine contractions of pregnancy. Keith points out the part played by the nodes in controlling peristalsis, and suggests that they act like a block system on a railroad, and control food progress by controlling sphincters. The endocrine glands secrete substances which Starling has called hor- mones; they act through the blood stream and form a most interesting chapter in visceral control ; they are closely allied to the sympathetic nerv- ous system, and are often found in glands of double function or glands that at one time have had an external as well as an internal secretion. The gonadial secretion derived from the interstitial cells of the generative or- gans controls sex characteristic even when the genital elements are absent. The relation of the external pancreatic secretion dealing with the digestion of fats, starches and proteins has only an indirect connection with the tissue of Langerhans, which has to do with sugar metabolism. The thyroid in the king scorpion is a reproductive gland, and the thyroid function in the human being is closely connected with puberty, in the female, with the pregnant state. Types of life are found in which the thyroid functioned through the digestive tract, and the foramen cecum at the base of the tongue in man marks the site where this secretion was at one time discharged into the intestinal canal. In the present stage of human development, the thyroid is entirely an organ of internal secretion ; Init through its influence on other endocrine glands, it assists in maintaining reproductive and diges- tive functions. The pituitary gland probably corresponds to the strainer gland in the fish stage, and in the course of development was left within the skull in- stead of on the side of the pharynx. It contains elements derived from the pharyngeal mucosa, and many of its tumors show pharyngeal heredity. Is it possible that this gland, which is so important in the growth of the body, is favorably affected through improved circulation by the removal of diseased adenoids and tonsils? Certainly one often sees a child of slow development, after an operation for removal of tonsils and adenoids, make a most striking physical and mental gain. The coccygeal body (gland of Luschka) has no known function, but it is connected with that stage of development in which the primitive hind or tail gut was part of the neurenteric canal. These pre- natal vestiges may be the source of dermoids or neoplasms of peculiar na- Page 399 RANSOHOFF MEMORIAL VOLUME ture, not infrequently malignant, lying in the hollow of the sacrum behind tl^e rectum and eroding the bone. Some theorists have called the external xe^titrial remnants of the neurenteric canal the posterior umbilicus, and be- licxe that tiie sequestration dermoids so frequently found in the lower sacral and coccygeal midline have this origin. Keith points out that the interna! secretions of the five important endocrine glands: pituitary, suprarenals, gonadial, pineal and thyroid, control racial characteristics of the three great divisions of man, Caucasion, Negro and Mongol. The sympathetic nervous system was a later develoiJment, and correlates visceral action. It stimulates the function of endocrine glands, and is in turn stimulated by their secretions. To the great English physiologist Gas- kell we owe our knowledge of the involuntary nervous system. His first work on the visceral nervous system was published in the early eighties. Gaskell pointed out that certain small-calibered medullated nerves pass from the anterior horns of the spinal cord to the great sympathetic ganglion of the thorax and abdomen, which connects the central nervous system with llie sympathetic. These connecting nerves enable emotions originating in the central nervous system to influence the sympathetic ganglion. From the synt|)atbetic ganglion small nonmedullated fibers pass directly to their dis- tribution forming the sympathetic nervous system. Gaskell also showed that there are nerves of the same kind which have visceral functions arising from the cranial nerves, and he called these para-.sympathetics. They are composed of the vagus nerve, the fibers in the third, seventh and ninth cranial nerves, and the pelvic nerve from the sacral plexus. The para- symiiatlictics are small-calibered medullated nerves with ganglion cells near their distribution, as in the heart itself and in the plexuses of Auerbach in the wall of the intestine. Neither the sympathetics nor the parasympathetics are under the control of the will, and when distributed to the same organ they follow Sherrington's law in that they are antagonistic. Langley, who contributed much to this work, called the combined sympa- thetic nervous system (thoracic and lumbar ganglions) and the parasympa- thetic (cranial and pelvic) the autonomic system. American physiologists, especially Cannon and Crile, have contributed largely to this work. Gaskell pointed out that the symjiathetic ganglions develop widespread reactions to slinnili which exercise inhibitory control over the vegetation system inde- pendent of the will, and inhibit the parasympathetics. The cerebrospinal nervous system produces a conscious and accurate action of the striated muscle system, but has no control, and only indirect effect, on the non- striated muscles. Langley. Crile, Cannon and Brown have made practical application of Gaskell's discoveries, showing how the fibers derived from the sympathetic ganglions, acting for defense, produce the most widespread and sudden effect when excited by emotions such as fear or anger. The digestive tract is teni])orarily (lepri\cd of function ; the heart action and resjjiration increase in rapidity and strength, the glands of internal secre- W. J. MAYO tion, especially the suprarenals and thyroid, are activated, and sugar reserves in tlie liver and body generally are thrown into the blood stream to enable greater muscular action. It is interesting to note that the nerves of Gaskell from the anterior horns of the spinal cord to the sympathetic ganglions are direct, and it is only those nerve fibers derived from the sym])athetic ganglions themselves that pass to the various organs to produce the widespread effects spoken of, with the exception of the suprarenal gland, which receives fibers from the cord en route. The suprarenal contains within itself true nerve cells, as though at one time a start had been made for a dififerent type of control from that which was afterward developed through the sympathetic gan- glions. 'I'he parasympathetics of Gaskell, as related to the gastro-intestinal viscera, are composed of the vagus nerve derived from the bulbar division of the parasympathetics, and the pelvic nerve from the sacral plexus. When the emotions, which, acting through the sympathetic system cause the sud- den necessity for instantaneous use of all the body reserves, have passed away, the vagus nerve comes into action and causes the heart to beat more slowly, and reduces respiration. The digestive tract, the stomach, intestine, liver and pancreas, which have been temporarily inhibited by the sympa- thetic fibers from the solar plexus, are stimulated to function through the vagus parasympathetic acting as a motor nerve through the plexus of Auer- bach, and the pelvic parasympathetic motor nerve again permits conscious control of the bladder, sigmoid and rectum, which had been inhibited by the sympathetic fibers from the inferior mesenteric ganglion. One may well be- lieve, however, that while these functions are checked by the sympathetic and are caused to resume action by the parasympathetics, control of their normal activities goes back to the nonstriated muscles, and the internal secre- tions which were the earliest forms of control. The gastro-intestinal tract is, therefore, largely controlled in its functions by the nonstriated muscle and by chemical substances acting through the blood. The sympathetic gan- glions act to inhibit these functions temporarily to produce rapid catabolism and spend reserves prodigally. The parasympathetics set in motion the in- terrupted anabolic activities and maintain reserves for future emergencies. It may seem that these well-known anatomic and physiologic details need no reiteration, and yet in my association and teaching of younger men in the profession I find that while they may know these facts, they often fail in their interpretation of them. The interpretation of the interesting phe- nomena which I have cited may not be correct in given instances; but if by "near-right" theories a dry subject may be made to live, the means will be justified and the strain on our memories will be less. We must not forget that memory training is the Confucian method which certainly has not led the Chinese in the ])aths of progress. Facts do not change. The interpreta- tion of fads constantly changes, and new interpretations of old and new facts are the source of ])rogress. ( )nly as we are doubtful of our interpreta- tions can we hope to advance scientifically. Papv ',01 THE NECESSITY FOR THE APPLICATION OF DIFFERENTIAL AIR-PRESSURE IN THORACIC OPERATIONS.* W'ti.ly Meyrr, M. D. New York. For the second lime tlie aniuial meeting brings together tlie members of tlie American Association for Tlioracic Surgery. This young organization, embracing members of the medical profes- sion who are interested in the study of diseases of organs situated within the chest, saw the light of day at the time of the meeting of the American Medical Association in New York City, on June 9, 1917, and celebrated its first birthday in Chicago on June 9, 1918. It would be difficult to begin this second meeting better than by re- peating the words with which the first, amidst a rising vote of thanks, was closed: "Our Association is proud and gratified to have it spread on its minutes that Dr. S. J. Meltzer, the renowned ])hysiologist and internist, the man who has done so nuich for the evolution of thoracic surgery, was its first president." If I might speak my inmost thoughts, I would say, I should have felt happy had there been no successor, and had Dr. Meltzer adorned the presi- dential chair for another year, nay, for life. But he willed it otherwise ; and so, gentlemen, by your kind choice, I stand before you as your pre- siding officer. Let me thank you most sincerely for the honor and your trust ; they are highly appreciated. The task of finding a topic for the time-honored presidential address has been made easy. Within the last year we have had new proof that the usefulness of what I consider the very foundation of modern thoracic surgery, viz., the principle of employing "differential air-pressure" in the course of our operative work within the thorax, has not yet been generally recognized in its importance as a life-saver. Hence, it appears to me appropriate that I should devote this address to a discussion of the place occupied in thoracic surgery by differential pressure apparatus, using the words in their widest sense, i. e., including all such apparatus and methods as we know of. In again calling attention to the necessity of their use in thoracic operations, I feel certain to be voicing not only my own personal opinion, but to be putting on record the sense of the majority of surgeons in this Association. Let us see just what does occur when a healthy parietal pleura is per- forated. \Miich are the symptoms and sequelae of the acute pneumo- thorax? Whicii are the ]>liysical and pathological conditions surrounding it. Copyright. William Wood & Company. JVILLY MEYER "Observing a deeply narcotized dog, whose pleura has been incised in experimental surgery, a very typical and characteristic clinical picture will be seen to develop. Immediately after the opening of the pleural cavity and the subsequent prompt retraction of the lung, a brief cessation of the respiration occurs by reflex. This is followed by sudden, almost projectile attempts at inspiration and expiration. The entire accessory muscular ap- paratus is called into strenuous action. The thorax moves up and down over the collapsed lung which is seen lying immovable in the depth ; its originally glistening surface has assumed a congested appearance, and its normal pinkish color has given way to a dark grayish-red. Soon the fre- quency and the depth of the respiration increase, as may be observed by watching the excursions of the chest wall. At the same time the respiration becomes irregular. After a few minutes the symptoms are less stormy, the respiration becomes quieter and more regular, but slower and dee]5er than under normal conditions. This slowing up of the respiration, which gradually increases, is produced by the lengthening of the expiratory phase. A little later only brief inspirations occur at longer intervals. Soon the respiration, and therewith, the heart's action stop completely.'' (Sauer- bruch.) Experiments further show that when both pleural cavities of the dog ;irc simultaneously opened, respiration soon ceases, subsequent to most vio- lent efforts of nature to hold back the waning life by means of very deep ins])irations and expirations. Death occurs by suffocation. In unilateral acute pneumothorax in the human subject, the disturb- ance is frequently less pronounced than in the dog, though it varies widely in severity in different individuals. For the alteration in respiration various causes are responsible. Tiie principal role is played by the mediastinum. The anatomical or- gans and parts composing the mediastinum divide the thorax into two com- partments, which latter are completely filled with lung. With the exception of the heart and large blood vessels the greater part of the mediastinal tissues represent a soft yielding mass, in which very little resistance tu lateral pressure is off'ered. Under physiological conditions the perfect equality of forces existing in the chest on both sides of the mediastinum keep the contents of tlvj latter in their normal position of rest. The part of the pleural sac that lines the mediastinal structures, chest wall, and diaphragm — mediastinal, costal and diaphragmatic pleura — is in close approximation with the other portion of the pleural sac that lines the lung surface — the pulmonary pleura. The narrow space, separating the two pleural leaves, is filled with a viscid lubricating fluid which establishes cohesion between their serous surfaces, but leaves them free to glide over one another, like moist panes of glass which can be relatively shifted, but not forced apart, unless air is made to RANSOHOFF MFMORIAL VOLUME get in between them. Contact between the two surfaces is upheld by the air pressure within the lung which is always close to atmospheric pressure/" Let us assume now that an incision of the chest wall has been made in ihe course of an operation, opening a "virgin" pleural cavity, viz., an intact cavity and without adhesions between lung surface and chest wall. At once air is admitted between the two pleural leaves, their cohesion is destroyed, and the air pressure on both sides of the visceral (pulmonary) pleura of the exposed lung is equalized. The elastic force of the lung tissue is thereby made active; the lung contracts to a mass of the size of a fist at its hylum — same as in the dog — and the opened side of the thorax is transformed into a cavity. Immediately the respiratory act becomes violently disordered. The excursions of the thorax leave the retracted lung unaffected, because there is no more contact between it and the chest wall ; its lobes have lost their function. On the closed side of the thorax, on the contrary, the co- hesion between parietal and visceral pleura, and therefore the function of the lung, has been maintained. However, under the difference of air-pressure on both sides of the mediastinum, when the thorax expands during inspira- tion, the mediastinal structures plus the collapsed lung and the heart with the large blood vessels, move forward and partly into the uninjured side of ihe thorax, the lung swinging like a pendulum suspended on the trachea as a rod. Inasmuch as the mediastinal contents are attached by means of the lower portion of the pericardium, also, to the diaphragm, the maximal lateral displacement occurs at about the center of the mediastinum. The whole mass moves in the same direction as the chest wall of the uninjured side, that means over towards the side of the lung which is still functioning, and interferes with its proper distention. The functioning lobes are thus, during inspiration, held near their normal expiratory distention, with a cor- respondingly reduced change of air in them and reduced oxygenation of the blood. In expiration the ]ienclulum swings the other way ; the whole mass flops back into the open cavitw a to-and-fro rocking of the heart subject- ing the large blood vessels to severe bending strains in alternating directions. The mediastinum is now no longer, as under normal condition, the evenly balanced structure, upon which, and upon the rising diaphragm as a cushion, the collapsing chest walls squeeze the air out of the lung through the nar- row glottis. With the mediastinum yielding to the one-sided pressure upon it, the air pressure within the lobes of the uninjured side only gradually rises high enough for escape of the tidal air by way of the glottis. A part of this tidal air rather finds an outlet into the incompressible portion of the •The intrapulmonarv pressure bcconips slightly reduced (negative) during inspinitioii, because the distention of tli^ tlvrrix r"Ti^ ^oni-wlinl ahead of the air volume a.lmittf.l itivML-li the glottis. On the other hand, ih, im vu.mIih.ii n > i,,,,sure becomes slightly increa-.l nn-nr,, . ,';,,inK expira- tion, because the :. i ...t allow the air to escape iiuic I ■ the thorax contracts. A si ji. ■ f.iees under plivsiological e^n' ' iDkable. It could occur only «ii. n. ,,i li. ,,i tln_. King to drop below the vain. i i ,, mi-nnal elastic retractive force ol liic Iuuk tl^■.uL■. -;iy ij mm. Hg. This latter force dineis .il vaiiuus points of the lung. It depends on the dtgiec of excursion of chest wall and diapluagm with which the particular part of the lung is in contact. At the apex of the lung and along the spine the retrac- tive force is considered to be practically zero; in front of the lower lobe it is ad maximum, varying .nt other points between these extremes. WILLY Ad EVER bronchial tree of the lobes of the collapsed lung where it has but atmos- pheric pressure to overcome, and not the additional obstruction represented by the glottis. Thus the main bronchus of the collapsed lung with its first and second divisions — which, as just stated, have retained their normal size and shape on account of the cartilaginous rings within their walls, same as (he trachea — becomes a "re-breathing bag" for the functioning part of the lung. In this way the collapsed lung appears to have an inspiration during expiratory movement oi the thorax, the air for it, however, not being fur- nished from without, but representing a part of the expiratory tidal air of the functioning lung; that means air which should have left the respiratory system by way of the glottis. The volume of the tidal air is thus still further reduced, with progressive vitiation of the shifted air. At the same time a persistent chronic "hyperemia" invariably develops within the collapsed lung on the injured side. Its presence there was proved by most interesting experiments conducted by Cloetta of Zurich, Switzer- land. This phenomenon has so far, it seems, not received the attention which it deserves. The hyperemia of the collapsed lung on the injured side nat- urally reduces the quantity of blood in the general system, which, as stated before, is altered in its quality by insufiicient aeration. The described interference with the normal exchange of gases in both sides of the lung causes a gradual accumulation of carbon dioxide in the .system. This, in turn, produces a steadily increasing irritation of the cen- ters of respiration and circulation by way of the pneumogastrics. In most instances this "vicious circle" soon becomes established after incision of the thorax. Respiration becomes slower and deeper, the number of heart-beats is reduced, while the systolic volume of blood is increased. Dyspnea in its most characteristic picture develops and persists. Such, in the human being, is the general course of the dreaded "acute pneumothorax." As stated above, it occurs only in a certain percentage of the patients, coming to operation. But who is able to tell beforehand "which" patient will be subject to its deleterious, or even fatal, sequelae? The symptoms of acute pneumothorax can not and do not develop, if we prevent the collapse of the lung; that is to say, if we keep the lung on the open side of the thorax in distention and thereby steady the mediastinum. This can be done by the employment of apparatus embodying the "differential air-pressure" method. Following upon scattered ingenious attempts at preventing the lung col- lapse with the help of apparatus, by French surgeons (Quenu, 1895, Tuffier, 1896), and American surgeons (Fell, 1888, Matas, 1898), it was Ferdinand Sauerbruch who, in 1904, by his experiments, his scientific investigations and his constructive genius, placed thoracic surgery on a safe basis. By the publication of his differential Pressure Method" and by his apparatus he gave to the surgical world the means for operating on all the organs situated within the thorax, under absence of disturbing physical conditions. He RANSOHOFF MEMORIAL VOLUME made it possible for the surgeon to operate within the thorax with the same tranquillity of mind and the same precision as in other cavities and parts of the body. The thoracic cavity thereby was opened safely to the surgeon, safely in the real sense of the word. viz.. without forcing the operator into taking chances with his patient's life. He also showed that, in case of injury to the intra-abdominal parenchyma- tous organs in the vault of the diaphragm (liver and spleen), work upon them could be safely done by the thoracic route (trans-thoracic laparotomy). The differential pressure method aims at substituting the eiifect of ap- paratus for the normal forces sustaining the lung, which were cut out by the opening of the thorax. The apparatus has to supply a force which is equal to the elastic contraction of the lung tissue. The power used is air-pressure. A difference in air pressure can be obtained : 1. By rarefying the air over the outer surface of the exposed part of the lung; that is to say, by producing there a pressure which is inferior to the atmospheric pressure within the bronchial tree and alveoli — negative (differential) pressure. 2. By increasing above atmospheric pressure the air-pressure within tiie entire lung — positive (differential) pressure. \Mthout exception all the various schemes devised for the neutralizing of the injurious effects of the acute pneumothorax are based on that alterna- tive, first pronounced in so many words by Quenje of Paris. Making use of either one or the other of these methods in patients suf- fering from dyspnea in consequence of an acute pneumothorax, one will see the latter disappear and respiration become normal again. One will also see that the lung on the opened side normally participates in the act of respira- tion. It is further a fact that differential air-pressure interferes neither with the normal respiration nor with the normal circulation of the blood.* The tangible, practicable result of Sauerbruch's labors was the negative chamber. Its construct ioi^. and working, its advantages and defects are known to my hearers. An amplified type of negative chamber, constructed on the basis of Sauer- bruch's principles, I had built in New York in 1908, and I experimented with it until 1910. It was then remodeled and became part of the apparatus of the Thoracic Pavilion of the Lenox Hill Hospital of New York City. It permits of working under negative as well as under positive pressure in the course of one and the same operation. The change from one pressure to the other can be effected instantaneously and without the necessity of reversing the position of the patient, assistants, instruments, ec, as would be required in Sauerbruch's chamber, were the pressure to be changed from negative to l)0.sitive. *.\ flight incTPasp in pressure lias been found in the pu'innnary artery witli some stasis in I pnlmonary vein, also some decrease in arterial blood pressure, when usinK positive pressure. Tto ever, the alterations are of no importance so lone as the differential pressure is not pushed, a this is never indicated. One can, therefore, claim that new risks are not incurred by the paiie who submits to the application of differential air pressure during operation. Page m WILLY MEYER The rectangular negative chamber at the Lenox Hill Hospital is so far the only one produced in America. Originalh' built as a portable apparatus. and being a first attempt, it is naturally open to improvement in one or the other respect. A round design has on occasion been discussed, constructed so, that the chamber, like other operating rooms, can be washed out with a hose stream; also additions on basis qf the Swedish chamber, in which the mask is used in combination with negative pressure, an improvement, which requires no modification of. but only a removable attachment to our present arrangements, and would insure undisturbed asepsis also in operations on the neck in the course of esophageal resections. The negative chamber is an enlarged pleural cavity. It takes care with the same certainty and reliability of a bilateral as of an unilateral pneumo- thorax. It represents the most physiological apparatus in existence for com- plicated intrathoracic work on weak and reduced patients. It permits of the use of differential pressure under general or regional and local anes- thesia. It is a splendid physical apparatus, which will always retain its scientific as well as its practical value. But the negative chamber is expensive and stationary. Surgeon, assist- ants, nurses and patient have to go to the apparatus ; the apparatus can not be brought to the patient. The same holds good for a number of positive (plus) pressure cabinets, in which the patient's head, that is to say, his bronchial tree, together with the anesthetist — entire or in part — are placed under increased pressure. Sauerbruch's work made a great sensatioii in the surgical world and met with wide recognition. It also started many minds devising means by which the same ends might be obtained with less expense. In quick succession followed the mask method Brat-Schmieden, Tiegel, Robinson (1908-1910), Meltzer-Auer's Intratracheal In.sufflation (1910), and Connell's pharyngeal insufflation (1912), adapted to thoracic surgery by Branower (1913). Tiegel worked out his apparatus on the basis of the experimental finding that lack of oxygen is the final cause of death in acute pneumothorax. He proved that 1 mm. pressure from a tank filled with pure oxygen suffices to avoid trouble. His splendid practical apparatus is extensively used in European clinics, and should, particularly for use in emergencies, form an integral part of the equipment of every operating room in our country, too. Tiegel's apparatus can be quickly wheeled to the patients' bedside, a feature of great value in case of trouble in the after-treatment of thoracic operations. Meltzer-Auer's intratracheal insufflation represents the simplest and most nearly perfect of all positive differential pressure methods. Every one of you knows of its well-deserved triumphant march all over the world, within the last eight years. In two directions the method calls for attention and skill — first, that introduction of the tube into the patient's trachea re- quires profound general anesthesia; and second, that a person is needed Page !,!» RANSOHOFF MEMORIAL VOLUME who lias been trained tu make the introduction of the tube into the trachea properly and gently, without doing harm to the patient. Intrapharyngeal insufflation, which was originally introduced by Karl Connell of the Roosevelt Hospital. New York, as a method of anesthesia, and later on adopted to thoracic surgery by \N'. Branower of New York, with the help of an ingenious portable apparatus, promises to become of greatest value for thoracic operations. By insufflating pure air. or air mixed with oxygen, into the pharynx, a sort of air-storage is formed in that local- ity, in sufficient volume and under sufficient pressure to prevent the flopping of the mediastinum in unilateral pneumothorax and to maintain proper oxy- genation of the blood. In a rough wav. foot-bellows and a plain rubber tube, introduced into the pharynx through tlie nostrils, can substitute the apparatus in case of emer- gency. Thus, we now have at our disposal four useful methods for maintaining differential air pressure, from which we can select according to inclination, opportunity, and the needs of the case in hand, four useful, practical dif- ferential pressure methods, which enable us to avoid the occurrance of acute pneumothorax. Many of us use such apparatus in our thoracic operations to good advantage and feel that we do not want to be without them. On the other hand, there are a number of colleagues of high standing who are unwilling to accejit dift'erential air pressure as an underlying prin- ciple in thoracic surgery, and claim that they are able to get along nicely without its use. Opposition certainly is wholesome and to be welcomed. It is necessary for the progress of science. But it must be opposition in the right direction. Of course, we all have to individualize. Why should not a surgeon, if he considers it advisable in a given case, do a thoracic operation without em- ploying differential pressure apparatus? I myself have done it in many cases. However, what I claim to be necessary, and always have had in my own cases, is some kind of differential pressure apparatus close at hand, ready for instant use, should the necessity for its use arise in the course of the operation and the patient's welfare demand it. To my mind the time has passed when any surgeon is justified in saying '"dift'erential pressure in thoracic surgery is superfluous." To my mind it is wrong to promulgate such views. For the sake of the proper evolution of thoracic surgery it is equally wrong, I believe, to want to give to the surgery of the lung a special, an ex- ceptional place in thoracic surgery, as some authors have lately been in- clined to advocate. We should not separate the surgery of the lung from that of the esophagus or any other intrathoracic organ, but should consider the whole field within the thorax an entity and look at it from a broad and scientific standpoint. We should not separate thoracic surgery into dift'erent categories. We speak only of "abdominal surgery." and there is only one "thoracic surgery." Page iOB WILLY MEYER In this connection I must briefly refer to the teachings that have of lale emanated from a number of great Euro])ean surgeons, who worked at the front during the last four years and recently traveled through our country lecturing on their experiences. Under the correct impression that air pres- sure difference was necessary for safe operating within the thorax, and having no apparatus at hand, they at first abstained in the war hospitals from active interference in chest wounds. Conservatism was their watch- word in these war injuries. But, compelled by many unsatisfactory results, they finally dared go ahead without using differential pressure, and saw ex- cellent results in many instances. With the object in view of removing all kinds of foreign bodies in the lung or pleural sac, they made an intercostal incision, cleaned the pleura, pulled out the lobe of the lung in which often the X-ray had previously located the seat of the foreign body, incised the lung, extracted the missile, stitched up the pulmonary wound, dropped the organ back, and closed the chest wall air-tight by suture. Many of these pa- tients recovered. But is it correct, on the basis of such satisfactory experiences in war surgery in a traumatized and often inflamed and infiltrated lung, and in- flamed or infiltrated mediastinal structures, to assert that the acute pneumo- thorax is something quite negligible, something not worth taking into con- sideration? Is it correct, on the basis of experiences gained under unusual conditions, to brush aside the well-matured conviction of a century that the acute pneumothorax rather is a matter not to be trifled with, to ignore the decades of endeavor to find means of overcoming its recognized dangers, and to draw the conclusion that dift'erential pressure is a ballast in thoracic surgery? I personally think that it would be an error to accept such a con- clusion. To my mind the operator of today has in times of peace no right to jeopardize and take chances with the patient's life, when science offers him the means of avoiding them. Would the surgeon of today dare omit any of the details of aseptic surgery, because the ingenious Spencer Wells, before the antiseptic and aseptic area, successfully performed a number of ovariotomies by simply washing his hands carefully in plain water before the operation? If a modern surgeon were to do his and lose one of his pa- tients he would be condemned, and justly so. Let us try for a moment to analyze the experience our colleagues have had at the front. For the sake of science it appears necessary to do so, to try to explain the seeming discrepancy between their experience and that had by surgeons when operating on the thorax at our public hospitals in times of peace. How can we explain the absence of worrying symptoms in many of the thoracotomies, when even five to six hours after the wound had been inflicted, the chest was opened freely by incision without the use of dif- ferential pressure apparatus? The fact has been established in the course of the war that over 50 per cent, of the men with chest wounds died on the battlefield. The surviving cases reached the ambulance or field hospital. In them the heart — usually Page Ifi'J RANSOHOFF MEMORIAL VOLUME young, strong, and not diseased — had withstood the acute pneumothorax and hemothorax, and the lung of the unopened side also had adapted itself to the changed conditions. If operated upon by means of an exploratory in- cision and without pressure apparatus, often the at first serious and threaten- ing symiMoms improved. Why? Simply because, as we all know, the wide open pneumothorax, the free access and exit of air. is better borne than tlie pneumothorax coming from a small penetrating wound, through wliich air has entrance, but very frequently an obstructed exit. After free incision air alone reiilaces the blood and air that formerly filled the pleural cavity. The mediastinal tissues are apt to be infiltrated with blood, so that there is little flopping. Besides, the surgeon pulls the lung out of the thorax and treats it as the case may require. The pulling out of the lung into the wound opening ( "Mueller's trick") steadies the mediastinum still further. The lung is then attended to, the pleura cleansed, and the thorax closed hermeti- cally by sutures ; a temporary artificial pneumothorax is left behind. The latter, as shown by Bastianelli's splendid investigations on the Italian front, favors the healing of the injured lung and its gradual expansion with ad- vancing absorption of air. The results obtained by our colleagues in military service by means of aggressive surgery in wounds of the lung have certainly been brilliant and deserve the highest praise. But to draw any sweeping conclusions from iheir experience zvith reference to the question of ivliether or not the em( 11 ,,354 1 S-VII 2.375,(HX> 11, .354 31% 17-Vll 2,435,000 3,820 46% IXA'H 3,4Q0,(KXi 5,154 46% 19-\"I1 3.!25,tXX) HI). Pyrodin Remarks 0.015 0.01 (Sahli) 0.02 0.02 0.03 0.02 0.02 Xo free Hh. in serum. 0.02 0.02 none .Animal weak. \\t. - 1,904 gnis none 0.02 0.03 Kresh 0.035 Serum RANSOHOFF MEMORIAL VOLUME Date R. B.C. W. B. C. HI,. Pyrodlii Remarks 1905 20-VIF 2.633,l!(M_) 8,660 37% (Sahli) 0.03 21-\-|I 2.26.%(I0() 0.03 Serum fainlv pink. J.'-\ll l.Qlo'dUi 15.466 26% i)M .Misccss ..f left ear. -M-\'ll I !(>.'() IHKI 18,688 25% 2?-\ll 1.93(l.(»!ll (Sr 26-Vll 1.9,?7,(HNt 9,622 34% 0.03 27-VII 2.24,\!5,0(K) 10.510 3S% 0.03 26-VII 1.262,(VI0 0.02 27-VII 950,(X«) 16.510 21% nnne 28-VII 1 775 (X)0 0.025 29-VII l,95O,0(XI 26,310 ,34% 03 30-^'II 1,85(>,()00 0.03 .M-VII 1,720,()(X) 19.8tX) 22% 0.03 l-\-III 1,480,0(X) 0.035 2-\'llI 1 ,365.000 21.044 22% " 0.03 3-\-ni 1,500,0(X) 0.03 4-\'III 1,375,(XX) 25,954 25% none 5-VIH 1,475,0(X) 0.03 Pyrodin by stoinaeli UiUc. 7-VIlI 2,1(X).(HX) 14,354 .18% 0.03 Pyrodin l)y stoniaeh tube. 8-\'III 2,230,(XX) 0.04 Pyrodin bv stomach tube. Q-\-TT! 2,125.000 30,250 25% 04 Fresh solution of pvrodin. !0-\-ni 1.415,000 0.04 Pyrodin by stomach tube. Death during the night. Autop.sy at 12:15 p.m. There was a small amount of clear, light yellow fluid in the peritoneum. Right lung showed moderate hypostasis and oedema. Otherwise the organs resembled in every particular those from rabbit I. ]\Iicuoscopic.-\L Ex.\MiN.-\Tiox. — The tissues from this rabbit, as well as those from the remaining animals, were all treated as in rablait I. experi- ment A. Bone Mamn^-. — This resembles in all respects that seen in rabbit I. In the smears, however, there are a few nucleated red cells which may be classed as megaloblasts. Spleen. — There is marked necrosis of the pulp and the Malpighian fol- licles are reduced in size. In places in the venous sinuses there are groups of mononuclear, non-granular cells like those in experiment .\. In one grou]) there were two megalokaryocylcs and several phagocytes, and in one of the non-granular cells a mitotic figure was seen. Haemosiderosis is marked. The erythrocytes ihroughout the si)ieen are for the most part ROGER S. MORRIS slirunken and distorted. Smears, stained as in experiment A, show very many cells resembling lym])hocytes with a moderate number of normoblasts and myelocytes which, however, seem less numerous than in rabbit I. There are many phagocytes and jiractically every red blood cell is distorted. Liver. — There is marked fatty degeneration, afifecting chiefly the cells of the central part of the lobule. There is no dilatation of the capillaries and no intracapillary nests of cells are to be seen. No megalokaryocytes are found. There is considerable hfemosiderosis. Smears show a few polymor- phonuclear pseudoeosinophiles, V^ery rarely one finds a normoblast or a myelocyte ; they seem to be about as numerous as they are in the heart's blood. Mastzellen are comparatively numerous. A few phagocytes are seen. Kidneys. — Marked h;eniosiderosis of the cortex; otherwise practically- negative. The remaining organs are negative. The spleen, which has been active in this experiment as a li;ematopoietic organ, has assisted the bone marrow in the attem[)t to compensate for the anaemia, but there is no evidence of hsmatopoiesis in the liver. Experiment C: Rabbit III. Male. Weight, 2,170 grams. Pyrodin given by stomach tube. Date R. B. C. W. B. C III). I'vnulin Kcniarks 1906 Il-IV S,()5(»,()00 9,020 53% (Micschcr) nunc 18-IV 6,025,(:O0 12,400 62% (Mil 19-1 V 5.820,000 0.02 2.3-IV 3,850,000 12,500 44% 0.02 Raliliit sccnis lifeless. 23-IV 3,487,000 0025 25-1 V 3,275.000 14,160 34% 0.04 26-IV 2,125,000 none 27-1 V 1,843,000 2S-1V 1,093,000 12,480 ■■3% 30-1 V 1,925,000 7,00<_1 39% ■' 1-V 3,441,000 8,600 47% 0.03 2-V 2,075,000 10.640 39% ;; 3-V 3,721,000 9.280 '• Difficult y in passing tube. 4-V 3,833,000 5.600 51% ■■ Difficult y in passing tube. 5-V 4,087,000 6.932 58% (1.035 7-V 2,975,000 12,532 42% 8-V 2,750,000 13,120 Z?,% 0.035 9-V 2,600,000 15,600 32% 0035 10-V 2,450,000 26,800 25% ;; 0.04 11-V 1,500,000 26.300 none 12-V 1.400.000 20,400 19% ;; 0025 14-V 2,312.000 5,849 0.04 15-V 2,300,000 6,620 26% 0.04 Fresh s .olution of pvrocbi 16-V 1,993,000 19,520 23% 004 17-V 1,858,000 8.700 15% none 18-V 1,730,000 7.464 16% I9-V 1,935,000 3,776 21% 0.04 21-V 2,566.000 4,088 28% 0.045 22-V 2.020,000 7,064 20% none 23-V 2.012.0(X) 17,600 22% 0.04 24-V 1,762,000 5,552 18% none 25-V 1,525,000 8.9<^1 17% 26-V 1,735.000 7.464 16% 28-\' 2,225,000 vm 28% 0.045 RANSOHOfl' MEMORIAL VOLUME DalL' K. B. C. \\. B. C. Hb. Pyrudii; 1906 J9-\" Z360.000 5,200 19% (Miesclier) 0.04S 30-\- 1.880,000 16.800 15% •• 0.045 31-V 1,293,000 21.500 12% 1-VI 1,044,000 18,932 11% 2-V\ 1.. Ml. 000 10.044 m Death occurred l)et\vefn If) :00 and 1 1 :()() a. in. un June- 4. UHY.. Autop.sy at 3 :00 p. m. There were .small yellowish nodules in the liver. >onie of which had ex tended to the surface of the organ ; they were slightl\ elevated, flat across the top, and rather finn in consistency. No areas of softening were found in them on section. In other respects the organs dift'ered. niacroscopically. in no essentials from those in the preceding rabbits. Microscopic. \i. E-K.v.min.vtion'. — Bone Marrcn^'. — There is marked hy- perplasia of the myeloid tissue, the granular marrow cells (myelocytes) be- ing in the majority. The islands or cell-nests described by P.unting are vveil seen and many of the large non-granular cells in the center of the nests show karyokinetic figures. Phagocytes are present. Tn the smears there are many free pseudoeosinophilic granules; there are very few intact myelo- cytes. Spleen. — This resembles the spleen in rabbits I ;iud II in the decrease in size of the splenic follicles, the diminished number of cells in the i^ulp, and the presence of a few megalokaryocytes. Phagocytes are jjresent in enor- mous numbers. A few pseudoeosinophile myelocytes are found in the pulp. In the venous sinuses and rarely in a capillary, collections of mononuclear cells resembling large lymphocytes are seen; at times a megalokaryocyte is present in these collections of mononuclear cells. Evidences of mitosis are not lacking in the cells collected in the venous sinuses. Smears show large numbers of nucleated reds, as many as six being found in one held (Leitz. 1/12 oil immersion; ocular. I\'). The majority of the nucleated reds are normoblasts, though there are many intermediates and rarely a megalo- blast ?). No definite cell division figures are found in the smears. There is a great number of lymphocyte-like cells resembling the non-granular, mononuclear cells of the bone marrow. .\ moderate number of jiseudo- eosinophile myelocytes is present. Mastzellen are very scarce. Liver. — The liver cells show little change other than ;i moderate pig- mentation of the cells of the peripheral zone of the lolnilo. In the liver capillaries, both in the central and peripheral zones, there are many pseudo- eosinophile leucocytes, mostly polymorphonuclear with only an occasional mononuclear. Megalokaryocytes are not .seen. Glisson's capsule is un altered. The nodules found at autopsy present a central necrotic area sur- rounded by granulation tissue. Smears show many polymorphonuclear pseudoeosinophiles. very few norninblasts and mastzellen. few pseudoeosino- phile mvelocvles. ROGER S. MORRIS J'lic remaining organs art nt-gative c.xct-pt for iiignK-nlation of tliu renii tex. \\\-ighi. 2,.^0U -rani>. I 'vrodin si\ e- Ex periniciil D : Rabl. ii l\ . Male. \\\-ighi. siibciit aneouslv. Dale K.I i.e. W. 1!. C. 1 11, I'vr.Hln 19t)6 12-IV 5,855,l->liO 4.176 55% uMic'SclK-ri none 18-IV 5,662,0a) 59% 0.01 19-IV 5,86O,0UO 6.800 59% 0.015 23-IV 5,612,000 51% 0.015 24-IV 4,820,000 5,200 44% 0.03 25-1 V 5,170,001 0.04 26-IV .\ 125.000 8,844 43% 0.03 27-IV 1,664,000 none 28-I\- 1.406,000 6,920 11% .^o-i\- 1.440,000 2,800 17% 1-V l,941,Um) 2.664 26% 2-\" .1360,000 2.488 39% 0.03 3-\" .1,1 64,000 3,100 45% 0.035 4-V 2,714,000 4,700 43% 0.03 5-\" 2,4(_)0,OUO 6,400 43% 0.03 7-\ 2.100.000 7,128 35% 0.03 8-V 2,125,000 13,800 25% •; 0.035 q-v 1.662.000 18,080 15% lO-V 1.237.000 4,932 18% u ii-\" 1.807,000 5.376 24% 0.025 ij-\' 2.014.000 3,864 28% 0.035 14-V 1,468,000 4,480 22% 0.03 ]S-\ 1,785.000 4,852 20% 0.035 16-\- 1,262,000 11.200 15% none 17-\ 1.750,000 4,932 19% \SA- 2.160.000 2,640 24% 0.035 19-V 2.050.aX) .1100 23% ;; 0.035 21 -V 1,281.000 3,360 12% wi-ak. l''nr roiit;li. Animal died between 11:00 a.m. and 1:00 p.m. on May 22. 1906. Au- topsy at 5:00 ]i. ni. Large red clots in both \entricles and extending into the aorta : |iracticaliy no fluid l)!ood in any of the vessels or organs. The latter are macroscopically the .'-ame as in rabbit I. As in the |)receding ani- mals, no lymph glands or hremolymph glands were found, MxCROSCOPTCAL EXAMINATION". — Boiic Mciirow. — The section shows marked hyperplasia of the bone marrow of the myeloblastic type. In tin smears the myeloblasts are by far the most numerous, the erythroblasts and granular marrow cells being relatively few in number. Spleen. — The alterations in the s[)Ieen resemble those seen in the three previous experiments, but they are less marked. Megalokaryocytes are present. Smears show, in addition to many lymphocyte-like cells, a few normoblasts and myelocytes. Liver. — Sections show very little alteration. In the smear only two nor- moblasts were found after prolonged search, not more than smears from ili.- blood showed, it seemed. Kidneys. — Marked pigmentation of the convoluted tubules is found. Lungs. — There is marked tedema and moderate congestion. In the capillaries one finds a few megalokaryocytes. RANSOHOPf MEMORIAL VOLUME Experiment E : Rabbit \' given by stomach tube. Female. Weight, 1,900 grams. Pyrodi Date R. P.. C. \V. 11. C. Hb. Pyro.liM Remarks 1906 16-X 5,500,()0() 8.200 61% (.Mi.-scI K-r) (Mil 17-X 5,sai,coo 8.240 62% (1,02 18-X 4,330,000 9,760 57% (l.(L' 19-X 4,310,000 6,240 48% (•.035 2a-x 3,425,000 none 22-X 2,055,000 23-X 1,840,000 9,280 29% •• 24-X 2,105,000 7,2CO .39% " 25-X 2.415.000 5.680 39% 0.025 26-X 2,880,000 7.760 40% • " 0.035 27-X 2,990,000 6,000 43% 0.045 29-X 2.410,000 7,360 34% 0.045 31-X 2,265,000 6,320 31% 0.04 1-XI 2,735,000 5,680 3S% 0.05 2-XI 2,600,000 3,680 29% 0.03 Fresli sol iition of pyrodin. 3-XI 2,5io,axi 6.160 26% 0.04 S-Xl 2,585,000 17.840 29% 0.04 6-XI 2,310.000 5.600 30% 0.04 7-XI 2,660,000 5.520 35% 0.045 8-XI 1,850,000 9.000 25% none 9-xr 2,070.000 6,640 30% O.M 10-XI 2,150,000 5.280 30% 0.045 12-XI 2,275,0(X) 7,040 30% 0.05 13-XI 2,090,000 4,720 26% none 14-XI 2,7.30.000 8.720 .34% 0.07 15-XT 2,775,000 5.760 31% 0.14 Rabbit was found dead at 8 :00 a. m. Autopsy at 1 1 :00 a. m. Rigor mortis present. Spleen 8.5 .x 1.5 .x 0.5 cm. Right lobe of liver greatly atrophied. Two small nodules in liver and the normal mottling of the organ lost. \'ery small amount of slightly reddish ascitic fluid. Otherwise the findings at section were the same as in rabbit I. MiCROscopicvL Examination. — Bone Marrozv. — Both sections and smears show myeloblastic hyperplasia of the bone marrow. Spleen. — The section resembles closely that from rabbit I\'. A few pseudoeosinophile myelocytes are seen in the meshes of the jnilp and there are a few megalokaryocytes. There are small nests of mononuclear, non- granular cells, which look like lymphocytes, in the venous sinuses. Smears of the spleen show many lymphocyte-like cells, rarely a nucleated red blood cell, and a few myelocytes. Lh'cr. — There is some cloudy swelling and i)igmenlalion of the liver cells. No nests of cells are to be seen in the capillaries. The smears are negative. Lungs show moderate (edema. There are no megalokaryocytes in the capillaries. The other organs. e-\cei)iing the kidneys which present tiie usual changes. are negative. Page l,>0 ROGER S. MORRIS Experiment F : Rabbit \'I. Female. Weight (?) — average size. Pyro- din given by stomach tube. Date R. B. C. W. B. C. Hb. Pyrndiii Remarks 1906 16-X 4,090,000 8,080 61% (Miesclier) 0.01 17-X 4,705,000 11,640 60% " ■ 0.02 18-X 4,025.000 8,640 52% " 0.02 19-X 4.260,000 10.000 52% " 0.0.35 2n-X .•^590 000 .Animal weak. 22-X 1,5.35,000 none At about 10:00 a. m. on October 23. 1906, rabbit died. Autopsy at 3:30 p. m. The organs were all negative except for marked anaemia. There was very little fluid blood. No bleeding on section of liver. Clotted blood in heart, arteries, and veins. Bone marrow grayish brown. Spleen, 5 cm. long. Microscopical ExAMiNATioN.^Bojir Marrow. — The fatty marrow of the femur is largely replaced by cellular myeloid tissue in which there are a few normoblasts and a few myelocytes, the majority of the cells being non- granular mononuclears (myeloblasts). There are many megalokaryocytes and a few phagocytes. Smears reveal nothing additional. Spleen. — The pulp is poor in cells. The capillaries and venous sinuses are greatly widened and filled with blood. The follicles are slightly di- minished in size. There is a moderate number of phagocytes. A few very small collections of mononuclear, non-granular cells are found in the venous sinuses. In the stnear.'; many cells resembling the myeloblasts of the marrow are present ; there are very few myelocytes and no normoblasts seen. Liver. — There is nothing unusual with the exception of a few giant cells in the liver capillaries. Smears show very few non-granular mononuclear cells like those seen in the spleen ; no normoblasts or myelocytes are found. Kidneys. — Slight cloudy swelling and pigmentation of the cortex. Lungs. — An occasional megalokaryocytic embolus is to be seen. No cause can be found for the rapidly progressive pernicious course of the anaemia in this case. The rabbit received exactly the same doses of pyrodin (and on the same days and hours) as rabbit V; in the one the blood count gradually fell till exitus lethalis occurred less than nine days after the beginning of the intoxication; in the other the fall in the number of the ery- thocytes was less pronounced and a fatal issue did not result. The probable explanation would seem to be, in part at least, defective powers of hasma- togenesis in rabbit \'I, such as one sees in the so-called aplastic pernicious anaemia in man. This assumption is further supported by the practical ab- sence of nucleated red blood cells from the circulating blood during the entire course of the anremia. In this case there was not. however, aplasia of the blood forming organs. It is true that there was not complete myeloid transformation of the fatty marrow of the femur, and evidence of hasma- topoiesis in the spleen, if present, was slight, but it is uncertain whether the hyperplasia of the blood forming organs in this instance is any less than that which might be found in the rabbit ordinarily after an acute an.'emia Page l/il UAX^OllOhl' MJiMORIAL VOLUME lasting a little iiiuix- than eight day,-. Xu alleratioiis. ulher than those char- acteristic of pyrodin poisoning, were found in any of the organs, and there is, therefore, a similarity lietween the result obtained in this experiment and certain cases of "aplastic" an.-emia in man, for in the latter the disease pro- cess results, it seems probable, from excessive blood destruction with little or no evidence of compensatory blood formation. The earliest attempt at studying haniatopoiesis in anccmia of adult ani- mals experimentally was made by Bizzozero and Salvioli (3) in 1881. .\fter venesection in guinea-pigs and dogs they found large numbers of nucleated red blood cells in the spleen, which normally contains few, as well as in the bone marrow. In rabbits, whose spleen contains no nucleated reds normally in adult life, they were unable to produce changes similar to those obtained in guinea pigs and dogs. They believed, as a result of their experiments, that the spleen was active in regenerating the blood. Later Gibson (4) re- peated their experiments on dogs in part, with the same result, and he made ihe observation that many of the nucleated reds in the spleen presented divi- sion figures in the nuclei, a point strongly in favor of their local origin. In 1890, there appeared the work of Howell (5), in which he was able to show that, after severe and repeated bleedings, and in some instances after a single strong hoemorrhage, nucleated red blood corpuscles were demonstrable in the spleen of the cat with every indication that they were multiplying there, though normally these cells are not found in the cat's spleen in postnatal life. Ill studying the spinal cord changes occurring in experinienial an;enii.i of rabbits produced by pyrodin, von \'oss (6) noted that there was a deposition of granular pigment in the spleen with areas of necrosis, fatl\ degeneration in the liver, and in the kidneys all stages of parenchyma- tous nephritis. Tallquist (7) directed his attention especially to the iron content of the organs of dogs, in which both acute and chronic anaemia had been produced by the administration of pyrodin and of pyrogallol, and was able to prove in many instances a marked increase in the iron of the liver with considerable deposition of haemosiderin in the spleen, kidneys, and bone marrow frequently. In my own experiments there was a marked reaction for hemosiderin in liver, spleen, and kidneys in rab- bits I and II, the only ones in which it was tried, but the equally marked pig- mentation of the cells in the remaining animals makes it probable that the same holds true in all six. In the bone marrow in my cxpcrinieiits the pig- ment is contained chiefly in phagocytes. In only one instance was fatty dc- degeneration of the liver found, as von \'oss reported, while in none of my animals were the renal changes sufficiently marked to consider the existence of a nephritis. \'ery recently Rothmann and Mosse (8) have studied the effect of chronic pyrodin poisoning in dogs and give additional results of the general findings at autopsy (Mosse). No changes were found in the lymph glands. The spleen, enlarged at autopsy as in the reports of all jire- vious workers, contained much pigment and the follicles were entirely i)ro- ROGER S. MORRIS served. The characteristic inilp cells were not well preserved. The kidneys showed the usual changes, they say, in the epithelial cells of the straight and convoluted tubules. HEemosiderosis of the liver was noted. Most interesting was the condition of the hyperplastic loone mar- row, similar to that described by Reckzeh (9) in dogs after jiyrogallol- ansemia. The cells often designated ■"Stammzellen" or myeloblasts were present in very large numbers, there were many normoblasts and few granu- lar cells. Unlike others, Reckzeh described megaloblasts in addition to nor- moblasts in the bone marrow. The marrow of the femur in my ex])erinients showed myeloblastic hyperplasia in all instances with the exception of rab- bit III, in which there was a chronic infection, a fact which may explain the large numbers of granular cells. Lastly, and of greatest interest in connection with the jiresent work. Hunting (10) in 1906 showed, among other things, that chronic ansemia of rabbits, produced by the administration of saponin, lead in some instances to collections of cells in the venous sinuses of the spleen, just as Meyer and Heineke had found in man and as I found in my first two experiments.' "The peripheral venous sinuses of the spleen were much dilated and crowded with cells of the marrow type chiefly of the erythrogenetic series, but in- cluding many megalokaryocytes and leucocytes. The nucleated red blood cells were grouped much as in the marrow and showed numerous mitotic figures. The veins of other organs are practically free from nucleated red cells, except for an occasional small group in the liver and the constant pres- ence of megalokaryocytic nuclei in the capillaries of the lung." In Bunting's rabbits the anamia did not become very severe, and this he attributed to tht- \acarious blood formation occurring in the spleen. It seems much more likely, however, that in some way tolerance to the poison was established, for in my first experiment, where evidence exists of hfematopoiesis in bone marrow, spleen, and liver as well, there developed, nevertheless, a profound anaemia with fatal issue. As in his animals, I have found megalokaryoytes in the capillaries of the lungs, but not constantly. They were not present in the liver capillaries in Bunting's experiments. The anaemia produced by pyrodin is due, not to any interference with normal blood formation, so far as is known, ])ut to a great increase in blood destruction. Pyrodin acts upon the red blood cells causing shrinkage and deformity, and as Heinz (11) has demonstrated, these effects are most pro- nounced about twenty-four hours after the administration of the drug. In my experimental animals the color index remained high, as in Tallquist's experiments. Fortunately in the present work, the complete blood examina- tion was made always between twenty-two and twenty-four hours after the administration of the pyrodin. The changes in the red blood cells will Ijc discussed in another paper. Suffice it for present purposes to say ihat the ileformities in the red blood corpuscles which Heinz described occurred in all of my rabbits. The serum was examined several times for the presence of s Mentioned in the prelimin-qry report, nt Meyer and Heineke, 1905 )]. v. RANSOHOFF MEMORIAL VOLUME free haemoglobin, but none was found, an experience similar to Tallquist's, where excessive doses were not employed. Study of the histological sections shows beyond a doubt, it seems, that the injured red blood corpuscles are taken u]> by phagocytes which are found in very large number in the spleen and in much smaller number in the liver and bone marrow. In a very short time all the injured cells are removed from the circulating blood, unless, pos- sibly, a few recover and are able to functionate. This phagocytosis of red blood cells occurring in the spleen, liver, and bone marrow in experimental animals is of particular interest , since Warthin (12) has demonstrated a like occurrence in the spleen, lymph glands, hasmolymph glands, and bone mar- row in pernicious anremia in man. We have, then, produced experimentally an anaemia which may be, and probably is, like primary pernicious anaemia in its origin; in neither is there hremoglobinaema, as a rule, though this may exist exceptionally, and in both injured red blood corpuscles are removed from the circulating blood by phagocytes found in the haematopoietic organs which possess the double function of forming and "cleaning" the blood. In embryos Kollicker showed many years ago — and it is now generally accepted — that the liver is the chief and earliest haematopoietic organ. Later in foetal life the spleen also assumes this function and finally the bone marrow becomes effective in blood formation. Toward the end of intra- uterine life, and in the early part of post-natal life the liver and spleen cease forming blood, a function which is reserved solely for the bone marrow. As was noted before, Ehrlich has shown the similarity between the bone mar- row of the embryo and that of many patients dying of pernicious anaemia. And Meyer and Heineke demonstrated a like analogy between the blood- forming liver and spleen of the embryo and the same organs in pernicious anaemia. They have also called attention recently to a further point of re- semblance of embryo's blood with that seen in ])ernicious anjemia in the existence of a high color index in each and elsewhere I shall bring forward still another analogy in the presence of "Howell's nuclear particles" in the blood of the human embryo and in that of pernicious anaemia in man. It is evident, therefore, that the work of Meyer and Heineke has marked a dis- tinct advance in the pathology of pernicious anaemia, in that they have shown, so far as it is capable of demonstration at present, that there is not a defective regeneration of the blood in pernicious anaemia (excepting aplas- tic anjeniia), but rather a very great increase in blood formation, the spleen and, in some instances, the liver assuming this function. In the present experiments it is not possible to prove absolutely that the liver and spleen have reverted to their embryonic condition and taken up the function of blood formation, but it is possible to say that they present the histological pictures seen in the liver and spleen of the rabbit's embryo dur- ing the stage of intrauterine life when it is believed that these organs are actively engaged in haematopoiesis, and the inference is, therefore, perfectly logical that their function is the same here as it is during fcetal life. That evidence of haematopoiesis exists in the spleen in practically all of my cxperi- Pagc VA ROGER S. MORRIS ments and in the liver in (inly one instance may be explained by the fact that the spleen, which is the last to assume its blood-forming power, is the first to regain it, whereas the liver, beginning its hsematogenetic function at an earlier period of intrauterine life than the spleen, reassumes it with greater difficulty. COXCLUSIOXS. 1. The anaemia produced in rabbits by the administration of pyrodin (by stomach tube or subcutaneously) is one with a high color index and re- sults from injury to certain of the red blood corpuscles which are then re- moved from the circulating blood by phagocytes in the spleen, bone mar- row, and liver. This resembles the condition found in pernicious anaemia in man. 2. The increased blood destruction leads to increased (compensatory) blood formation. 3. The stimulus to increased regeneration of the blood, whatever its nature may be, leads to heightened activity of the hsematopoietic function of the bone marrow, the occurrence of myeloid elements in the spleen and occasionally in the liver. 4. The changes occurring in the liver and spleen in the experimental animals are similar histologically, so far as the haematogenetic cells are con- cerned, to those seen in the normal rabbit's embryo at certain stages in its development, and it may be assumed, therefore, that the spleen and liver have taken up their embryonic function, i. e., haematopoiesis. 5. The return of the embryonic function is in the reversed order of its disappearance. 6. Haemosiderosis of the organs occurs as in pernicious anaemia of man. 7. The weight of experimental evidence favors the theory of increased blood de,struction ( the toxic theory ) rather than that of decreased blood formation as the chief factor in the production of primary pernicious anaemia in man. For illustrations see original publication. REFERENCES. 1. Mevfi- anil IUmmIc I - i.^ . I ;l iiiljildi.nK in .Milz iind Leber bei schfeven AnSmien Vcv- hanill. tl ileiit^chen i.ail i l:.l 9. i>. 22A. 1905. 1 ■" ■ ?'lir' Tl''l"'r' ' '■ I'I'ilJnnR bci schwcren Aniimien und Leukamien. Deutsclles ■' lli/zciz!.!.! and ^ • ^ l: HI LL- zur Hamatologie. Molcschott's Untersuchungen. Bd. 2, ' ' , \ ' ' I'l ll.iinnni; ciiKans and Blood-formation. Jour, of .Nnat. and Pbysiol.. li... 1 ,,<■ l.ilV lli^idiy ,.f the Formed Elements of tbe Blood, Especially tbe Red Col- li. V. \osM .\natoniisclie und experimentelle Untersuchungen liber die Riickenmarltsveran- derun|,en hei Anamien. Deutscbes Arcliiv. f. klin. Med., Bd. 58. p 489. 1897. 7. Talldvist: Ueber expt-i imentclle Blntgift-Aniimieen. Berlin. 19C0. 8. Rollimann and Mosse: Ueber Pyrodinvergiftnng bei Hunden. Deutscbe med. Wochenschr.. Bd. 32, p. 187, 191)6. 9. Reckzeh: Ueber die dnrcb das Alter des Organismus bedingten Verscbiedenbeiten der ex- perimentellen erzeugten Blutgift-Anamieen. Zeitscbr. f. klin. Med.. Bd.- 54. p. 1(j5. 1904. 10. Bunting: Experimental .\n:vmias in the Rabbit. lour, of Experimental Med., Vol. 8. p. 625, 1906. 11. Heinz: Morpbologische Veranderungen der rotben Blutkorperchen durcb Cifte. Virchow's .Archiv., Bd. 122, p. 112. 1890. ous An.-tmia, with Special Reference to Changes Oc- Jour. of Med. Sciences, \-ol. 124, p. (,74. 1902. CLINICAL CONSIDER. \TI().\ OF OSTEOMYELITIS."^ A. J. OciisN-Ku, .M.U.. LL.D.. F.A.C.S.. AND D. \V. Ckii.i:. F..S.. M.D.. Chicaso. It has seemed worth while to consider osteomyelitis from the standpoint of the clinician hecause circumstances have favored us with an oppor- tunity of ohserving an unusally large numljer of cases suffering from thi- affliction. ^Iv observations began thirty-four years ago when 1 served as assistant to Professor Moses Gunn. who treated a very large number of these cases. Following his death, I served as chief assistant to Prof. Charles T. Parkes for a period of three years, and after his death as chief assistant to Profes- sor Nicholas Senn for a period of four years. Each of these surgeons had a great number of cases of osteomyelitis ; hence my sjiecial interest in this subject. In my own practice at the Augnstana Hosjjital during the twenty years from Jaiuiary 1. 1S99. to January 1, 1919, I have treated 301 cases of osteomyelitis, so that the following views are based upon the treatment and observation of a sufficiently large number of cases to be worthy of consideration. My assistant, D. W. Crile, served in France and England for a period of three years during the recent war. where he had an oppor- tunity of observing several thousands of cases of osteomyelitis due to gun- shot and shell wounds, and he likewise is interested in the subject. Osteomyelitis is a disease, inflammatory in nature, involving bone and having its origin practically always in the medullary tissue, although at times it may originate beneath the periosteum ( 1 ). and also as Lejars (5) says: '■Frequently there are two foci; imp. subperiosteal, and fine in the medulla." Osteomyelitis may Ije subdivided into the acute infecti\e tvpe, the sub- acute infective (occurring during the separation of sequestra and including rarifying and condensing processes in the bone), and chronic osteomyelitis in which the infecting organism determines a further sulxlix ision into pyo- genic, tuberculous, or syphilitic. As a matter of fact, the division of infective osteomyelitis into an acme, subacute, and chronic stage, is purely arbitrary, and often can be accom- plished only with the greatest difficulty, since the disease is a progre.ssive one. However, as a general rule, the acute stage may be said to occupy the period when a general systemic reaction exists characterized by fever, loxsemia, an increased pulse-rate, intensive pain, always located near the affected part and generally being dift'use over the entire neighborhood. The subacute stage may be said to begin when the tox?emia has been overcome * From Surgeo'. GynecoloRy and Obstetrics. September. 1920. ' Read before the Chicago SurKical Society, February 6. 1920. Page .}?« A. J. OCHSNIiR AM) D. IV. CHILE and Mippmatiuii still exisl>. The chronic stage constitutes that ]ieriod i:i which the bone cavities exist. It is possible for the acute stage to be absent, clinically, so that when first discovered the disease may be subacute or it is possible for both the acute and subacute stages to be negative clinically so that when first dis- covered, the chronic stage exists. This, however, is due to the fact that the early stages were looked upon as rheumatism, growing pains, or neu- ritis. Clinically, the tuberculou> and syphilitic forms should occupy a sepa- rate classification. They are cbrotiic, although each may be subdivided mh) an early and a late stage of the disease. Their course. i)athology, aud treatment are quite different from that of the pyogenic forms so that the\- will not be considered at this time. AX ATOMV The disease dejx-nds for its location and characteristics ujion the faci that bone is a rigid and peculiar structure composed of a hard, sparsely vascularized cortex and a soft highly vascular core (the medulla), and i circumferential vascular covering, the periosteum. All bones contain these three structures. However, they are present in varying proportions. The long bones, such as the femur, tibia, fibula, humerus, and the bones of the forearm contain the greatest proportion of hard tissue and in these the medulla is a true core. This core is trans- formed info a spread-out. flat structure in the flat bones, but occupies the same relative position to the cortex. If one saws through a bone, the outer layers are found compact while the medulla is found to be cumpnsed of an interlacing of thin spikes and spicules having attachment to the cor- tex. The ditterence in these two portions is pronounced, the cortex beinj; composed almost entirely of solid matter while the medulla contains large spaces between the spicules, in which there are fat, marrow cells, thin walled blood-ves.sels, and a considerable amount of blood. Ilowcxer, close in.spection shows that the union between these parts is not an abrupt one and that it is often impossible to say at what point the marrow becomes the cortex. Howexer, in the femur and humerus and to a less extent in (he tibia a definite medullary cavity exists in adolescent and adult life — the shaft of the bone being hollowed out more completely than the ends. This cavity contains true medullary tissue; fat, lymphoid cells, and h;emoblastic centers. On breaking a long bone transversely, one is able to .see that even the densest part of the femur is pierced by tiny canals, each contain- ing a blood-vessel and the larger ones containing lymphoid tissue. These canals are smallest in diameter directly beneath the periosteum where they are about 1/1000 of an inch in diameter and as one progresses toward the medulla, they gradually increase in diameter until at the place \vhere the cortex merges into the medulla they are about 1/200 of an inch in diameter. In the medulla itself they attain a very much greater size (IKO- These RANSOM OFF MEMORIAL VOLUME canals are nothing more than the tubes in which the blood-vessels lie and are called haversian canals after Clopton Havers, an English physician of the seventeenth century. Each haversian canal is surrounded by a series of concentric columns of bone, which columns are divided one from the other by concentric rings of single, little, thread-like processes which com- municate from one cell to the other and with the central tube of the haver- sian canal. These cells are called the lacunse and their thread-like processes are called canaliculi. The concentric layers of bone which are really fused into one column and the adjoining columns which are fused together mak- ing a continuous plate, are called lamellje. Between the lamellae and between the concentric groups of lamellse. one finds here and there irregular spaces which evidently are a result of the absorption of hard bone. These spaces are called haversian spaces. Virchow (2) says that each of the cells occu- pying the spaces between the lamellae is nucleated and Kolliker (3) is au- thority for the statement that some of the processes from these cells are connected with the periosteum and undoubtedly they also communicate freely with the blood-vessels of the haversian canals. It will be seen from this survey of the structure of bone that neither the cortex nor the medulla should be considered a crystallized or an inanimate substance. As a matter of fact, one has a better conception of the true na- ture of bone, if he considers it as a deposit of organized mineral salt be- tween the spaces of a finely-branched system of blood-vessels. Not only is the entire bone permeated by canals containing blood-vessels and living cells absorbing nourishment from these blood-\essels, but lymphatics also most probably exist (4). The periosteum is also very vascular and is a rather coarse, fibrous mem- brane, particularly where it afifords tendinous insertions. It can be divided microscopically into three parts : the one in immediate contact with the cor- tex of the bone, consists of strands of fibers containing quite a number of granular corpuscles, particularly in the young animal. These corpuscles are precisely the same as those one finds bordering the haversian canals, and it is possible that they are similar to the bone corpuscles found in the lacuna. Surrounding this division of the periosteum is a layer of elastic fibers, and the outer part of the periosteum again becomes composed of white, fibrous strands containing many blood-vessels, which ramify and prepare to enter the openings of the haversian canals of the cortex before they penetrate the elastic layer of the periosteum. These blood-vessels in the periosteum appear to have some muscular tissue in their walls, but the vessels which enter the bone are devoid of muscle (except the nutrient ar- tery). The blood supply of the bone comes also from nutrient arteries which gradually enter the medullary cavity by a hole running obliquely through the compact cortex, and in the long bones the artery generally enters near the middle of the shaft. There are generally a few nutrient arteries entering the bones near their ends, but for the large part the fora- Page ^SS A. J. OCHSNER AND D. IV. CRILE niina which one ^ees near the end of bones are for the emission of veins. There arc two main nutrient arteries for the femur. The course of blood lliroiigh a bone. Arterial blood enters a bone through two routes, the most evident route being via a nutrient artery which, after it reaches the medulla, sends blood both up and down the bone, rapidly dividing into an arborization, the branches of which are short, emptying quickly into comparatively large venous spaces. The other route of arterial blood is via the periosteal vessels, the arborization having already occurred in the periosteum — when following this route the arteries are lost track of almost immediately and capillary vessels conduct the blood through the haversian canals in which it may be said to become venous at once. It seems that this periosteal blood penetrates a very little distance into the bone, compared to the distance that the medullary prenutrient supply does. One can readily see how this comes about when one remembers that the haversian canals have their smallest diameter near the circumference of the bone. The blood issuing from the cut surface of live bone alwavs exhibits the characteristics of venous flow, except when the nutrient artery itself is cut. For these reasons arterial blood, on entering the proper bony circulatory system, loses much of its impulse and becomes static. One may compare the entrance of l)lood into a bone with that of the entrance of a stream of water into a tank. Eoci of infection. Therefore, any organisms contained in the blood and brought by the blood to a bone, find their first opportunity to rest at the point where they enter the interosseous circulation. This point may be either directly beneath the periosteum or in the medulla at the point where the branches of the nutrient artery enter a blood-space. With the stasis of the blood, the bacteria settle and begin to multiply, undisturbed by a blood current. In this way bacteria which are not virile enough singly or two or three together to make a home for themselves in a more active tissue, are enabled to begin an infective process in the bone. Having multi- plied to sufiicient numbers, they excite a little inflammation in the delicate cells lining the blood space. These cells swell and leucocytes and fibrin accumulate, shutting off this blood space from the remainder of the cir- culatory system. This can occur easily because bone encloses the blood space in all directions except its entrance and exit, so that swelling must occur only toward the cavity of the space and can not occur circumferen- tially. From this little focus toxins and young bacteria disseminate, repro- ducing and extending this same process. We know that this is true from clinical experience, because the primary focus in acute osteomyelitis is practically always in the shaft and corresponds with the arborization of the nutrient artery as a general rule, occurring most frequently at the places where stasis is greatest, e. ;/.. on the dia[)hyseal side of the epiphyseal lines and at the cortex of tiie bone. .At both these places the blood-vessels are narrow, and the blood current \ery sluggish. It is true that in many cases there seems to be a simultaneous involve- RAA-SOHOl'F MEMORIAL VOLUME ment of tht Mibperiosteai region and the niedulla. bin while thi.s is pos- sible it seems most hkely that the i)roce>s begins in one or other of these locations and rapidl)- extends through the communicating blood spaces from the medulla to the subperiosteal region, or vice versa. Lejars has noted the frequency of this occurrence and advises that whenever an accumula- tion of pus is found beneath the periosteum, it should be opened widely, even though no other indication exists — for a medullary abscess is im- dout)tedly present. ilACTHKlOLOtiV Almost an\- organism may be found in osteomyelitis. By far the large majority of cases are due to the ])resence of the ])yogenic cocci (6). and the staphylococcus is the organism most frequently found. Streptococcus in all its strains, the typhoid bacillus, the pneumococcus, the colon bacillus, the Klebs Loeffler bacillus and others, have all been found in this disease, so that it is quite evident that the disease is not dependent on a specific organism. Neither is there any proof that any particular strain of or- ganism exercises a selective action for the Ixme marrow . IXCIDKXCK 01-- DISl'-.A.sl-; (Jsteonixelitis occurs most frequently in the adolescent boy. In a series of 104 cases at the Copenhagen Hospital, it \\as found that boys were affected three times as frequently as girls, thai tin- liones were affected in the following order: femur, 39; tibia. ,M and Innncrus. 9; fibula. 7; radius. 4 and ulna. 2. ( )ur ex])erience confirms this sequence. It is interesting to note the greater frequency of the femur since this bone has more nutrient arteries entering it than any of the otiier long bones. The long bones are much more frequently involved than any of the others. The infrequent incidence of acute infectious osteomyelitis in the vertebr;e is interesting when compared with the incidenci- of tuberculosis of the vertebrae, and in this connection we would like lo point out that perhaps there are many cases of the disease in this region which are in- correctly diagnosed until spinal meningitis is manifested and as -nch prove- fatal. There is no doubt that trauma i>redisposes to the localization of the condition at the site of bony contusion. This is the true explanation of the greater frequency of the disease in boys, although the latter are also more subject to exposure. The disease often follows exanthemalous fevers, typhoid fever, pneu- monia, acute pleurisy or the presence of a hidden focus of infection any- where in the body. \\'hen following these diseases it is plainly the result of a haematogenous transportation of the germ. It is believed that the presence of infected tonsils, infected teeth, disease of the middle ear or sinuses, or chronic appendicitis, are often responsible for the origin of the bacteria causing this clisca^e. in its acute stage, it sometimes is only a A. J. OCHSNER AM) P. IV. CHILE manifestation of a septicemia or a iJVjeiiiia, aiul in these most serious con- ditions, multiple foci often exist. Ho\\e\cr. the disease does not neces- sarily indicate this grave condition. PATHOI.oC.N Early in the acute attacks the medulla i- congested centerin,s( ahnut the focus of infection. The periosteum oxerlying the involved region is hy- persemic, pinkish in color, and heavy with cedema. It feels tense and ruh- bery, but there is no actual j)itting as one sees accompanying inflammation in the subcutaneous tissues. On separating the periosteum from the bone, bleeding is more evident than it is in the normal condition, indicating that the tiny blood-vessels which enter the haversian canals from the periosteum are dilated in their attemiJt to carry an extra amount of blood to the in- jured area. One notices this hy])era?niia in the cortex itself in some cases when the marrow cavity is opened, for the congestion is quite marked. The normal fat tissue which ordinarily will not flow has a melted appearance and oil may even be seen oozing from the marrow spaces. At this incipient stage one may find no pus whatever, and it is during this time that opera- tion accomplishes the most good, since if the medulla is well drained at this time, the infection may be checked absolutely so that medullary and cor- tical necrosis do not occur at all. One may discover this stage on the first or second day, but, as a general rule, abscesses are present within twenty- four hours of the onset. The abscess centers about the initial infarct and. if not seen until considerable pressure has been developed in the medulla, secondary aljscesses will be found often at c|uite a distance from the primary focus. It is not at all uncommon to find the entire medulla of the bone full of pus. At this stage of the disease, which may be encountered at any time after the first twelve hours, one fre(|uently finds subperiosteal ab- scesses as .well, which have developed from the medulla tlirough the ha\er sian canals to the subperiosteal region or \ ice versa. Epiphysitis. — The epiphysis becomes invohed in 12 to 15 pVr ceiu of the cases and between the second and seventh day of the disease. When the epiphysis does become involved further growth of bone from the epi physis may be arrested particularly, if actual separation has occurred. As a general rule, the disease is limited to the diaphysis, the epiphyseal cartilage acting as a block against extension of the process into the joints. And also the close adherence of the periosteum at the epiphyseal lines checks the extension of subperiosteal suppuration towards the joints. This in counter-distinction to the characteristics of tuberculosis. However, the joints proximal to the acute infection commonly show distention, the dis- tending fluid being a protective outpouring of lymph into the synovia, and the fluid in these joints is very seldom infected. At times this fluid max even show traces of blood and the synovia are oedematous and hyperremic. Sequestration. — After frank jnis has appeared in the medulla, one hardly expects to prevent llie necrnvi^ which generally follow- o>teomye- RAXSOHOFF MEMORIAL VOLUME litis. The inflaniinatory pressure which develops simultaneously with pus in tiie bones causes a shutting oft' of the blood and nourishing lymph to certain parts of the involved bone. Thus these parts die, and, after varying lengths of time, are separated from the living parts. The separation of the delicate medullary bone occurs more quickly than does cortical sequestra- tion. Thus medullary sequestra may be loosened after two weeks, while the cortical sequestra generally take from four to eight weeks in separating. The separation seems to be accomplished through the activity of certain marrow cells termed osteoclasts whose function it is to destroy all unneces- sary bone. However, it seems that the presence of pus itself has some solv- ent action upon dead bone and this action is demonstrated by the gradual disappearance of small sequestra which are constantly bathed in pus. This solution of sequestra is a long and slow process which may be aided by chemical stimulation, but surgical removal of sequestra after separation is our practice. Character of Pus. — As the acuteness of the process decreases, the char- acter of the pus changes gradually, until in the subacute and chronic stages the pus becomes a thin, serous fluid lacking the milky rich appearance of the pus found in the acute condition. The very initiation of the process, how- ever, is generally accompanied by a very thin, almost clear exudate, and this is particularly true when the offending organism is the streptococcus. Rcfair. — Reparative processes begin sinniltaneously with the formation of sequestra which may be single, multiple, or the entire shaft may become a sequestrum. Inflammation stimulates the bone-producing mechanism, and it is not long until new bone begins to appear beneath the periosteum. It seems that this does not come from the periosteum itself but from bone element left clinging to the periosteum and nourished by the ves.sels of the periosteum. After three or four weeks, the periosteum begins to have a brittle feel much like the crackling of delicate tissue paper, and gradually the layer of new bone nourished by the periosteum assumes a definite thick- ness and gradually loses its property of being molded until after eight or ten weeks a definite shell of new bone surrounds the old dead bone. This new involucrum is poor in quality. It is honeycombed with spaces through which pus escapes from the neighborhood of the enclosed sequestrum or sequestra. There may be only one small hole through the involucrum but where mul- tiple sequestra are contained, many cloaca are found and often the new shell ot l)one is so fenestrated as to resemble a very imperfect lattice work. Tiie new involucrum may be very imperfect in its reproduction of the original bone. Particularly is this the case when entire portions of the shaft have been destroyed and the limb has not been kept in its normal shape by orthopedic appliances. This most often occurs in the upper arm and thigh since in these parts there is only a single bone. In the leg and forearm where a second bone generally retains its shape, deformity does not so readily occur. New bone is also formed from the medullar}- region, but this bone is not so imi)ortant pathologically since from its position it can not surround A. J. OCHSNER AND D. W. CRILE dead fragments, and therefore is more homogenous and of better quality than is the subperiosteal bone. Granulation tissue is more generally found growing from the medullary region than from the periosteal region, and it seems that the chief efforts from the core are directed toward the removal and destruction of sequestra and bacteria, while the efforts of the circumferential tissues seem to be di- rected toward the reproduction of supporting bone. So far as the pathology of the chronic stage is concerned, it makes no diiTerence whether the acute process has been cut short by surgical intervention or whether nature has accomplished the overthrow of the acute infection. In either case the suc- cessful outcome will have been accompanied by the creation of an exit for the pus, so that in the later stages one sometimes finds sinuses leading from the sequestra to and through the skin. If these sinuses are the result of the spontaneous evacuation or of insufficient incisions through the perios- teum in draining the abscesses they may be very long and devious. An ab- scess arising in the medulla at one end of a bone may not find egress from the interior of the bone until it reaches a point quite a distance from its origin. Here it breaks through the cortex to the subperiosteal region, where it may travel still further from the original focus before it makes exit through the periosteum into the fascial planes overlying. This is most likely to occur near the insertion of a tendon and from this point the pus generally travels along the tendon sheath toward the surface where, after a superficial abscess is formed, rupture occurs. Frequently the spontaneous sinus has a direct course to the surface and when this is true it resembles the sinus resulting from surgical drainage. In either event the sinus in the chronic stages is lined by granulation tissue. The granulations which spring from the interior of the involucrum, together with those that line the sinus, pour out a thin chronic discharge. Often the deeper granulations assume characteristics which have led French writers to call them "fongosites." These "fongosites" are overgrown, poorly nourished, oedematous masses — when cut they do not bleed as healthy granulation tissue does. They have a sickly gelatinous appearance and almost always indicate the presence of a sequestrum. When the sequestrum has been dissolved, discharged, or re- moved, the cavity of the involucrum fills slowly and incompletely with these granulations depending from the lining membrane of pseudo periosteum. These involucral cavities persist for great lengths of time and seldom fill in with healthy tissue. As time goes on the involucrum becomes very dense, and this is particularly true where there have been multiple small cavities and sequestra while the bone at a little distance suffers an atrophy. These two conditions may be seen in the same bone or one or the other may be present alone. The sclerotic condition is termed condensing osteitis while the other is rarifying osteitis. The pathology of the chronic condition which wc iiave described is gen- erally absent altogether following thorough primar\' surgical interference, but these changes are so frequently present they must be described. I'a.jc !,.U RA.VSOHOFF MEMORIAL VOLUME In considering the pathology of this condition, one must also remember that the overlying soft parts may suffer changes dependent upon infection, disuse or deformity, and likewise contiguous joints may suffer from actual infection or secondary reactions. SYMPTOMS Intense pain is the most striking symptom of acute osteomyelitis — pain so severe that the patient's perception of one's intention to touch the limb elicits agonizing shrieks. In severe cases the vibration of a bed from people walking nearby causes pain and the slightest motion of the affected limb is intolerable. The pain may be preceded by, but generally precedes, a high fever, a rigor or a succession of rigors, general toxaemia, and sweating. Soon the affected limb becomes swollen, heavy, and inflamed; the swelling is generally diffuse, as when the femur is involved the whole thigh becomes tense, red and tender. In the leg or forearm the oedema is apt to be most pronounced over the aft'ected bone. The joints are usually not swollen nor tense in the first few hours, but may rapidly fill with serum and result in the appearance of an arthritis; in these cases the limb ma}- be held in the typical positions of the various arthritis. The temiJerature rises acutely to very high levels, 103° to 105°. and is of a continuous type with little variation between morning and evening. The patient is generally unable to sleep. The pain is not definitely localized but involves the entire limb. The pain becomes worse on lowering the limb, as one would expect since in this position congestion is increased, and, therefore, pressure on the nerves is increased. When the bone is involved subcutaneous tapping on it at a distance from the focus will cause pain at the involved area. In case of an abscess or before an abscess is formed, induration may be found over the site, par- ticularly when the subperiosteal focus is present. In the less acute type the pain is of a constant character, described as an aching, located in the bone, and resembling the so-called growing pains. These cases occasionally show a slight febrile reaction, present one day and absent for an interval. Sometimes the patient will refuse to use the limb as, after use, the pain increases. The subacute type may or may not be jiainful. There is generally an occasional spell of fever with malaise in the part. This spell may be precipitated by changes in the weather or over- exertion. The surface of the bone may show nodules and irregularities. The chronic type without sinuses is seldom di.scovered in boys and girls and in older j>eople often simulates and is probably diagnosed as chronic rheumatism. It is this type that includes the circumscribed bone abscess and bone-cysts. The chronic stage of the acute disease is almost always made evident by the presence of a discharging sinus. D1.\G.\0SIS Acute infective osteomyelitis must be dift'erentiated from acute rheu- matic fe\er which can usually be accomplished by noting that the affection Pane Mi A. J. OCHSNER AND D. IV. CRILE is extra-articular. When cuntigiious joints are swollen secondarily, how- ever, the differentiation is not easy. When this condition exists, tapping over the bone at a point farthest from the joint, may cause pain in the bone, while in an acute rheumatic joint, such tapping may be painless unless the joint be moved. The presence of a single synovitis argues against acute rheumatism. One finds, too, that the skin overlying the joints is less red and redematous when the synovitis is secondary to osteomyelitis. The gen- eral prostration, while it may be great in both the diseases, is often greater in osteomyelitis. Sometimes the joint contiguous to the osteomyelitic bone can be moved painlessly, but this is rare ; one must always dift'erentiate be- tween acute osteomyelitis and an early stage of infantile paralysis. At times this is very difficult. The presence or absence of stiffness of the neck is very important in this differentiation, and whenever two limbs are in- volved one can safely rule out osteomyelitis, as the disease rarely begins with a double focus except as evidence of a general pyaemia. The acute arthritis of infants generally occurs in the hips and knees and is most often found in nursing babes and may be associated with a gonorrheal ophthalmia or vaginitis (8). In very young children one must always bear in mind the possibility of the presence of scurvy, which can be readily recognized be- cause it affects many joints. Acute arthritis deformans, especially when occurring in children, may be very difficult to differentiate. Generally the arthritis is multiple, how- ever, the prostration not nearly so sudden, the temperature not nearly so high, and the joints less tense. All these conditions, however, can be ex- cluded by the exact localization of the process outside the joint, and gener- ally on the diaphyseal side of the epiphysis. The condition should not be overlooked in its earliest state when it is usually considered a strain or sprain or contusion, since a history of trauma is frequent. The X-ray is of little or no value in the diagnosis of the early acute stage except in a negative way, since it may confirm the presence of periosteitis, tuberculous or syphilitic disease, or fractures; when medullary abscess for- mation has occurred, an excellent X-ray plate may demonstrate the condi- tion, but the diagnosis should be confirmed by one who is thoroughly fa- miliar with the shadows seen in this condition, since they are often very faint and illy defined. The later stages of the disease when bone cavities, cysts and sequestra exist are readily detected by the X-ray. PKOG.XOSIS The prognosis of the acute disease is always grave. When death occurs it is generally during the acute condition, and one finds pyaemia, infarcts in lungs, kidneys, liver, brain and vegetative conditions of the circulatory sys- tem as well as multiple foci of infection. These conditions may be the result of an unattended asteomyelitis, but often are concomittant evidences of hjematogenous infection from some common area. Early diagnosis with immediate surgical treatment modifies the gravity Page i-tr, RANSOHOFF MEMORIAL VOLUME of the condition considerably, but one should never predict that a limb with unimpaired function may result. Often when the focus is virulent and extensive and early treatment has been neglected, when the general reaction is extreme (the type of case which appears to have been "hit by a sledgehammer"), amputation has been recom- mended as offering the best hope of recovery. In our experience this ex- treme measure has never seemed indicated, although patients have frequently been sent to Augustana hospital for this last hope. In these cases it has always been possible to change the condition by laying open the periosteum and overlying soft tissues, applying an enormous hot moist boric acid and alcohol dressing covered with a large rubber cloth which serves the_ pur- pose of retaining heat and moisture and at the same time acting as a splint, and by applying a therapeutic lamp over this dressing. In a small group of very severe cases it is advisable not to chisel open the medullary cavity of the bone at the primary operation. With early and thorough surgical drainage one may not expect the process to spread into the neighboring joints, even though synovitis already exists in them. When the focus is close to the epiphyseal line, separation of the epiphysis may follow with the resultant loss of the power of growth from that end of the bone. At times the extreme virulence of the disease results in the destruction of the osteogenetic powers of the tissues so that the bone will not regene- rate. Rarely, the opposite result obtains, /. e., bony overgrowth follows the chronic type. With early surgical intervention witliin the first few hours of the dis- ease and in the absence of pyaemia, the focus being well away from the epiphyseal line, one may expect recovery with a functioning limb even in extremely serious cases after a long period of disability and with the re- mote prospect of several secondary operations for the removal of sequestra and for the obliteration of the sinuses. TREATMENT Acute infectious osteomyelitis does not seem to have been recognized until comjjaratively recent times, the explanation probably being that the abscesses finding their way to the surface, obscured the deep pathology and the cases were treated simply as very grave attacks of boils. The treatment of the acute condition so commonly practiced until re- cently with poultices, blisters, fomentations, sedatives, cupping, antipyretics, salves and ointments or manipulation and the healing arts, should be most heartily condemned. The only proper method of treatment is surgical drainage, splitting and reflecting of periosteum over the entire distance and at least two centimeters beyond and on each side, and opening the medullary cavity freely in the area involed. Combined with or follow- ing this, ilie i)art should be immobilized by splints so arranged that dress- ings can be done without disturbing the splint. Fomentation in the form Page .(36 A. J. OCHSNER AND D. IV. CRILE of hot moist dressings seems a valuable adjunct to this procedure, and any of the above mentioned remedies may be emi)loyed as accessories without harmful effect except treatment by manipulation. The use of therapeutic lights over the limb is a very valuable adjunct to drainage as they supply heat without the necessity of disturbing the limb. It also seems that the heat waves produced by means of electric light are more penetrating than those produced by the application of ordinary fomentations, hot water bags and electric jiads. OPERATJOX The patient is anesthetized, the limb is cleaned and painted with tinc- ture of iodine. The incision is made down to the periosteum avoiding arterial regions and the nerve-trunks and placing the incision so that it will drain in a dependent fashion without pocketing. The periosteum is freely incised in a longitudinal direction, and if it is not already separated from the bone by the presence of a subperiosteal abscess, it is raised by scraping it from the bone by a sharp rugine such as Oilier devised. The blunt periosteal elevator should not be used nor should the periosteum be stripped roughly from the bone. A sharp, thin-bladed chisel serves the purpose admirably, handled with great accuracy and gentleness. Rough treatment would result in leaving the osteogenetic elements on the bone and would leave the periosteum impotent to produce new bone. A hole is now made through the cortex with a trephine or a drill or by chisel and mallet, great care being taken to avoid undue jarring of the bone before the operation is begun or during the operation. It may be necessary to make several holes through the cortex, although this is rarely necessary if the point of greatest tenderness is carefully located. In the very early stages one may find no frank pus whatever but the marrow will be oily, serous and oedematous-looking. When this condition or the pres- ence of pus is discovered, a large slab of cortex should be removed, leaving the remaining bone in the shape of a trough. One should chisel sufficient cortex away in both directions from the focus that he may be sure that no secondary focus remains undrained. The further advantage of this procedure is that any incipient focus, too early to be detected grossly, will be nipped in the bud and will not progress to a destructive stage. The marrow or the exposed area should be removed with a curette and the walls of the cavity remaining may be washed with an antiseptic solution. For this purpose carbolic acid (5 per cent) seems ery efficacious. In virulent infections, pure carbolic acid may be used, ap- plied on a cotton swab and allowed to remain from two to five minutes. After this time it should be diluted with alcohol and the cavity thoroughly washed out with alcohol (95 per cent). In jilace of using carbolic acid, alcohol alone may be used or ether may be used, and of late Dakin's solu- tion has come into favor for this purpose. Tincture of iodine is excellent. The use of various antiseptic pastes does not seem so successful in the Paac -).^7 RANSOHOFF MEMORIAL VOLUME treatment of ilie acute stai;;e. although the bismuth, iodine, paraffin paste seems to have a favorable effect. The cavity may be packed with iodoform gauze or plain gauze to prevent the accumulation of a blood clot after operation. The presence of clots during the acute stage is dangerous and may lead to continued suppuration. The use of Carrel's treatment seems to give good results. Stewart and McCurdy declare that 3^4 per cent iodine is the best antiseptic and that packing interferes with the forma- tion of a blood clot, in this way interfering with bone repair. It is most likely that the cases in which a blood clot is desirable are not at all the type of case that we are considering since the presence of lilood clot in this class of cases almost invariably leads to further septic developments. The wound is left open. Rosenberg says that streptococcus and pneumococcus epiphyseal sup- puration often heals spontaneously and that the treatment in nursing in- fants should be limited to the opening of abscesses (10). He may, how- ever, have confused the acute arthritis found in infancy with an acute osteomyelitis. One should hesitate in making a diagnosis of osteomyelitis in suckling infants for this reason. In my own cases of osteomyelitis in infants the results have been amazingly good following simple incision. It seems that Lejars and Robert LeConte (11) agree that it is never expedient to incise the periosteum only, but that in all cases of periosteitis in the adolescent, it is wise to expose the medulla. If no medullary pus is found little harm has been accomplished, while if a medullary focus has been neglected great harm may ensue. My experience has borne out this plan except in the very violent cases described above (A. J. O.) LeConte favors the early removal of all bone and marrow involved and says that regeneration will occur if operation has been done early. This corresponds with the work done by E. H. Nicholls, of Boston (12), who, writing in 1904, thought that the periosteum itself deposited new bone after this operation. There can be no doubt that new bone is generally of good quality, reproducing the shape and function of the bone which has been removed. This is particularly true before the ossification of the epiphyses. The bone-forming elements which iremain attached to the periosteum are very active at this time of life. It would seem that in order to understand these results, one must believe that inflammation of the bone loosens the bone-forming elements from the periosteum. Our observations have convinced me that it is never proper to remove the shaft of a bone during the acute stage of osteomyelitis before an in- volucrum has been formed, because the resulting arms and legs have been infinitely superior in all cases where there has been a late removal of the sequestra. Based on the experience of handling many thousand cases of trau- matic osteomyelitis during the great war, it would appear that when com- plete subperiosteal excision of a section of shaft is done within a few hours of inoculation, regeneration occurs with more difficulty and more Page .',38 A. J. OCHSNER AND D. IV. CRILE often fails to occur than if the same operation is performed later. In traumatic osteomyelitis, excision of a section of shaft bone after inflam- mation has manifested itself by congestion and thickening of the peri- osteum, is hardly ever followed by failure of regeneration by the forma- tion of subperiosteal callus. This is particularly true where the bone- scraping technique of Oilier has been followed as described by Leriche (13). When this technique has been skillfully employed, even before the periosteum is inflamed, regeneration almost invariably occurs. These facts argue that the scraping of the bony cortex and inflammation in the same region result in leaving bone-forming elements adherent to the periosteum. This explanation of the question makes it clear that subperiosteal re- sections of bone in acute infectious osteomyelitis are not to be feared pro- \'ided operation is never performed in this condition before the appear- ance of inflammatory symptoms. This simple fact, /. c. that inflammation always preceded operation in this condition explains the regenerations whicii Nicholls so fortunately enjoyed but which he attributed to the periosteum itself. The work of Nicholas Senn, on the other hand, based on the classical experiments of McEwen (14). gave remarkably favorable results. He did not favor the excision of the entire shaft at an early stage, but advocated the operation providing radical drainage, leaving a shell of bone to be dealt with as indicated at a subsequent operation. Nicholls agrees with this idea when the disease is located in either the femur or the humerus, since these bones can not be excised without considerable deformity and shortening re- sulting. In the case of one of the bones of the leg or forearm, its fellow serves to maintain the length and shape of the limb so that this element does not enter into the question so seriously as it does in the thigh and arm. Taking all things into consideration, it seems that the best treament of the initial stage of the disease is immediate incision through the periosteum, thorough exposure of the medulla, leaving enough supporting cortex to pre- vent deformity and in such a shape as not to interfere with drainage and leaving a layer of bony scales adherent to the reflected periosteum, the dis- infection of the exposed tissues with tincture of iodine, the packing of the cavity with iodoform gauze to be removed on the second or third day, and the provision of free dependent drainage. This treatment should be instituted immediately on making the diagnosis. One must be careful to avoid the epiphyseal cartilages in doing the opera- tion, since injury to this area results in a hindrance to further bone-growth from the injured end of the bone. When the infective process itself involves the epiphysis there is no other course to adopt, except that of thoroughly clearing away all diseased tissue, since if the surgeon be hindered by timidity, it is possible for the process to extend into the contiguous joint, when ampu- tation may result. It is wise to mention the possibility of the subsequent shortening which one anticipates so that the patient and his relatives may know what to expect. Page l.TO RAXSOHOFF MEMORIAL VOLUME Supplementing this operative treatment, tlie limb should be immobilized and local heat supplied, either as fomentation with hot boric acid and alcohol dressings or by using an incandescent lamp so arranged that its heat is di- rected on to the limb, or a combination of the two methods, the lamp tend- ing to maintain the heat of the moist dressing. The patient should be freely purged, and for this purpose castor oil excels all other drugs. The patient should be given an abundance of good water to drink, and often by giving water in the form of lemonade, aerated waters, mineral waters, or weak tea. larger amounts may be drunk than if only plain water were offered. Large amounts of water provoke a diuresis and this, coupled with the purging, tends to increase the excretion of the toxins which the patient has absorbed from the diseased bone. With this treatment, the infection is rapidly overcome and no further extension of the process should occur. The after-treatment consists in the remoxal of the gauze packing on the second or third day, or sooner if the temperature does not fall the day after operation. It is seldom necessary to insert rubber drainage-tubes, if the case has been diagnosed and operated on in the early hours of the disease. However, if the case has not reached the surgeon until the entire medullary cavity is filled with frank pus. or even after the pus has begun to burrow in the soft parts, it is wise to remove the packing after twelve to twenty- four hours and to replace it by one or several drainage tubes, and this type of case will do very well when treated by Carrel's method, with frequent irrigations through many fine tubes, each one leading down to the bone cav- ity. The wound should be kept open while it heals by granulation from the depths. It is occasionally possible to suture these wounds at their pri- mary operation, leaving a corner of the wound open to pertnit removal of the gauze pack and for the insertion of a drainage tube, if necessary. If doubt exists as to the wisdom of closing the wound at once, it should be left wide open and closed at a second operation after healthy granulation tissue appears. This should be postponed, however, until the wound has become free from infection, which can be determined by examining the secretion microscopically. One must bear the fact in mind that the presence of bac- teria is proof of infection, but that the absence of bacteria microscopically is not sufficient evidence to prove that a wound is sterile. The cases which are not seen by the surgeon until actual necrosis of a section of the shaft, or, for that matter the entire shaft, present greater difiticulty. It is in these cases that immediate excision of the necrotic bone should never be practiced. I have been impressed with the importance of this rule many times in cases in which it seemed impossible to have any portion of the shaft of a long bone restored to normal. In these cases we employed the treatment described above of splitting all of the soft tissues longitudinally down through the periosteum for a distance of two to five centimeters beyond each end of the area apparently infected and elevating the periosteum from its attachment to the bone for a distance of one centimeter each side of this in- A. J. OCHSNER AND D. W. CHILE cision and then applying hot, moist, boric acid and alcohol dressings and ])lacing a therapeutic lamp over all. It has been surprising in many of these cases how small the total loss of bone has been ultimately. The bone which seemed hopelessly dead in many instances seemed to act in the capacity of a bone graft, being replaced to the greatest extent by new bone so that ultimately only a very small portion of the bone was lost. In one case, a girl of fourteen, in whom the attack was unusually vio- lent, an incision over the entire dorsal surface of the first metatarsal bone showed this structural black from end to end ready to be removed entirely. The treatment described above was employed and in twelve weeks the wound was completely healed without the loss of any portion of the bone. The entire bone served as a bone graft. The healing has been permanent. In my experience this observation has never been repeated to the same extent but a sufficient amount of bone has been saved in a large number of cases to convince me that much value should be placed on this plan of treatment. The important point to be gained comes from the fact that this treat- ment directs the lymph stream away from the substance of the bone so that there can be no advancement of the pathologic process, while, on the other hand, all of the natural forces can proceed with the work of restora- tion. Whatever can not be repaired by nature can be accomplished surgically later on at leisure when the patient has recovered from the acute condition and when the element of sepsis has been eliminated and the surgeon has to deal only with end-results of the disease. CHROXIC OSTEOMYELITIS The experience of the war has been of great value in furnishing ex- perience in the treatment of chronic osteomyelitis, although conditions are not exactly parallel. The important lesson universally learned corresponds with the experience of the few civilian surgeons who had a large experince with chronic osteomyelitis before the war, namely : ( 1 ) that in order to succeed one must remove absolutely all dead substance. In war surgery this means foreign substances in addition to sequestra which are alone to be considered in civil practice. (2) Provision must be made for filling the defect after all foreign bodies and dead bone has been removed and every portion of the remaining cavity has been throughly freed from infectious material. Methods of closing the defect. My earliest experience with these cases was as an assistant of Moses dunn, in whose clinic we treated a great num- ber of cases of chronic osteomyelitis. After removing all sequestra and producing a smooth cavity he tried to obtain healing from the bottom by keeping tlie external wound open l)y means of a paraffin plug. RANSOHOFF MEMORIAL VOLUME This plan ])roved very satisfactory although somewhat tedious. I also had an opportunity of observing many cases treated in the clinic of Charles T. Parkes who was my surgical chief following the death of Professor Gunn. 'IMie same plan of treatment and the good results continued. For a number of years following this experience, I assisted Nicholas Senn in the treatment of many of these cases. After thoroughly removing all sequestra and infectious matter and smoothing the cavity in the bone, he chiseled away a sufficient portion of the involucrum to permit the edges of the wound to unite without the slightest tension. Then the cavity was carefully disinfected with 5 per cent carbolic acid and throughly dried ; then finely cut, decalcified bone chips, which had been preserved in 1:1000 corrosive sublimate solution, were dried and sprinkled wilii iodoform powder and carefully packed into the ca\ity in sufficient quantity to fill the cavity barely full. Then the edges of the wound were carefully sutured so that the coaptation was perfect. A very large dressing and immobilization splints completed the operation. The results were ex- cellent. The reason why the method has not received more extensive adoption lies in the fact that few surgeons work with sufficient accuracy to carry out every detail of this procedure which is necessary in order to pre- vent the breaking down of the implanted graft. Moreover, the simpler method introduced by Max Schede about the same time brought identical results. Moorhof introduced a plug about the same time which we used with equally good results in a few cases but which we abandoned again because the results seemed no better than with Schede's method. This method consists in the steps described in connection with Senn's method to the point of filling the cavity, the technique then being as follows : The cavity is left empty and the wound is closed by means of a double row of continuous catgut sutures the first row acting as tension sutures and the second row as coaptation sutures. An Esmarch constricting bandage is left undisturbed until the very large dressing supported with a number of splints has been applied and the patient has been returned to his bed with the limb elevated in order to prevent the cavity to fill moderately with a blood clot which may remain undisturbed because of the character of tli,' dressing until it has become throughly organized. In each of the three methods described last the element of absolutely preventing any disturbance of the clot filling the cavity in the bone is of the very greatest importance. The failure to appreciate this fact has resulted in most of the bad results following the use of these methods. In cases in which there is not sufficient tissue to cover the cavity the method described by Emil Beck of carrying what skin is available toward the bottom of the cavity without tension has given very satisfactory results. In a number of cases in which the healing has been too slow, we have covered the granulating surface with Thiersch grafts. It is amazing to see how these troughs will fill up after covering the granulations with Thiersch grafts. Occasionally we have loosened long later;il flajis and have united A. J. OCHSNER AND D. W. CRILE these in front over the defect in the bone and then we have covered the defects on each side by means of Thiersch grafts. RECURRENCE In our cases recurrence has seemed to be due most commonly to the fact that during the primary treatment the source of infection was overlook- ed so that the patient sufifered from a re-infection rather than a recurrence in the usual sense of the word. Many of these patients state that they had a cold or a sore throat or a toothache just before their osteomyelitis recurred. Upon making a careful examination one finds a buried tonsil containing an abscess or an abscess at the root of a tooth or some other focus of infection. For thirty years we have removed these infected tonsils and roots of teeth in many cases in which recurrence had occured, and the patient has repeatedly remained free from trouble for a number of years. Trauma is another common cause of recurrence. Apparently some slight injury determines the return of infection to a Ijone that has previously been the seat of osteomyelitis. Sugar. Patients consuming large quantities of sugar are subject to the developement of furuncles and carbuncles and occasionally this seems to be an element in determining the occurence of recurrent osteomyelitis. Cold and exposure. We have seen a number of recurrences following exposure to cold and wet. In these cases, however, there has been an in- fection of the tonsils, the sinuses or the air passages. We have not been able to associate osteomyelitis with the occurence of intestinal disturbances although a priori one would suppose that this might be a source of infection. CONCLUSIONS 1. An early concise diagnosis and immediate surgical treatment is of the greatest importance. 2. The operation should invariably consist in splitting the periosteum for a distance of 2 to 5 centimeters l)eyond the area of pain upon pressure in the bone in each direction. 3. The periosteum should be loosened from the bone for a distance of 1 to 2 centimeters on each side of the incision. 4. In extremely severe cases this should be the extent of the primary operation. 5. In less severe cases ultimate healing can be hastened by carefully opening the medullary canal at the point previously located because of pain upon pressure. 6. Care should be employed to prevent traumatizing the tissues by rough chiseling. 7. Moist hot antiseptic dressing with fixation of the extremity and with the use of electric light treatment increases the comfort and facilitates healing. Page !,l,f. RANSOHOFF MEMORIAL VOLUME 8. The shaft of a long hone should never he removed until a good involucruni is formed. 9. In late cases or in secondary operations upon cases treated as ahove in the acute stage, every ])article of dead tissue must he removed. 10. At this o]:)eration some defnnate iilan must he carried out to facilitate closing the defect. 11. Skin grafting is of great value in many cases. 12. Local foci of infection such as abscesses of tonsils or teeth or sinuses, should invariahly he eliminated at once upon undertaking the treatment of patients suffering from osteomyelitis. REKKRENTK.S. 1. Coplin: Manual of Pathology, p. 718, la. Ouanin's Anatomy, Vol. 1. 2. Virchow : De periliori o.'^sium structuria, p. 17, Fig. 6. 3. Kolliker: Wlirzl,. Xat. Zlschr., Vol. I, 296. 4. Cruikshank: Anatomy of the Ahsorhing Vessels. 5. I.ejars : Urgent Surgery, pp. 550-554. 6. Delafield and Prudden : Textbook of Pathology, p. 886. 7. Alfred C. Wood: Acute osteomyelitis in children. Penn. M. J., 8. Clement Lucas: Quoted by Sir Wm. Osier. The Principles .ind Pr: p. 378. 9. Powell: Carbolic acid in surgery. Med. Record. 1899, Iv. 372. 10. Rosenberg: Osteomyelitis in suckling infants. Muenchen. med. Wchn 11. Robert LeConte: Acute inflammation of long bones. Boston M. & .S 12. E. H. Nicholls: J. Am. M. Assn., 1904. U. R. I.eriche: Treatment of Fractures. I'niv. London Press, Ltd., 1918 14. Nicholas Senn. A RAPID METHOD OF PNEUMOCOCCUS TYPING.* Wade \V. Oliver. nrooklyii. Dccausi.' of its prognostic value and also because it is necessary for s])e- cific serum theraj)}-, a number of methods for the determination of pneumo- coccus types have come into use. The standard methods up to 1917 are reviewed by Blake," special emphasis hcinij placed on intraperitoneal inoculation of the mouse with washed sputum and aRRlulinin and precipitin tests of the peritoneal exudate. Avery ^ reports a rapid cultural method for the determination of pneumococcus types in lobar pneumonia. By the use of a meat infusion broth with I per cent, glucose and 5 per cent, rabbit blood, sufficient growth usually is obtained within five or six hours for precipitin test made with the clear fluid. In order to still further save time, Mitchell and Muns' describe a method for de- tecting pneumococcus precipitinogen in sputum, 5 c.c. of which are ground in a small mortar with sand until a paste is formed. Then 10 c.c. of normal salt solution arc slowly added and stirred into the mixture and after three or four minutes, the dis- solved sputum is pipetted off, the solution centrifugalized at 2,2nO revolutions per minute for from five to ten minutes, and a precipitin test made with the clear fluid. Krumweide and Valentine ■* suggested a coagulation method for the rapid deter- mination of precipitable substances in the sputum. As in the method of Mitchell and Muns, considerable quantities of sputum are required, a decided objection against the method in certain cases in which only small amounts of sputum can be obtained. From 3-10 c.c. of sputum in a test tube are placed in boiling water until a "more or less lirm coagulum results. The coagulum is then broken up with a heavy platinum wire or glass rod and saline is added. Just enough saline should be added so that, on subse- quent centrifuging, there will be sufficient fluid to carry out the test." The tube is again placed in boiling water for several minutes, after which centrifugalization is employed. The supernatant fluid, which is the antigen, is then floated over 0.2 c.c. of undiluted antiserum. "If a fixed type was present in the sputum, and should the sputum have been rich in antigen, a definite contact ring is seen in the tube containing the homologous serum. With sputums less rich in antigen, the ring may develop more slowly and it will be less marked." The test that I describe is based on the solubility of the pneumococcus in bile. Taking advantage of the fact that in a typical case of lobar pneu- monia the infecting type of pneumococcus is often found in predominating numbers in the sputum of the patient, 1 c.c. or less of such sputum, imme- diately on its receipt in the laboratory, is stirred in sterile salt solution and bile added. After the protein has gone into solution in the bile, the mi.xture is filtered and a precipitin test is immediately made with the filtrate. The series on which tiiis test was used comprises twenty-five cases. On an aver- Keceived for publication June 26, 1920. * Fror.1 The Journal of Infectious Diseasc>s, October, 1920. 'Jour. Kxper. Med., 1917, 2C, p. 67. "Jour. Am. Med. Assn., 1918, 70. p. 17. 'Jour. Med. Res., 1917-8, 37, p. 3,19. •Park and Williams, Pathogenic .Micro-organisms, li/JO, p. 318. RAN so HUFF MEMORIAL VOLUME age, the time for effecting a t_vping was from twenty to thirty minutes. The results follow^ : Methods U.mployed and P.neumococcus Types Cases Pneumococcus Types Rapid Precipitin Aver y's Method Mouse ! — — NeEative Ne Xe i — Ne irativc Eativf \ Ne 4 Ne Xe 4 3 i >"e 1 Kativc _!. rativc XcKative — V^ native Xe ative (>lreptococeus1 ~ (streptococcus) We note that four cases belong to type 1, three to type 2, three to type 3. and eleven to type 4. A direct smear of the sputum, a selected fragment of sputum being chosen, is stained by Gram's method, as examination of sucli a smear is of distinct value in determining the presence of the pneumococcus as well as its relative numbers in the sputum. Next 1 to 1.5 cm. of sputum are placed in a clean test tube which contains a glass rod. Normal salt solution is then added, small quantities (0.1 to 0.2 c.c.) being added at a time and vigorous stirring w^ith the glass rod following the addition of each portion of solution. After from 0.5 to 0.8 c.c. of salt solution have been stirred into the sputum, from three to five drops of undiluted ox bile are added and the mixture thoroughly stirred. The amount of salt solution to be added is dependent on the consistency of the sputum, the endeavor being to obtain a fairly homogeneous specimen of a sufficiently fluid nature to admit of filtration or centrifugation. The tube is then immediately placed in a water balh, in water at 45 to 48 C. for ten to twenty minutes, which suffices for solution of the pneumococci by the bile. The fluid is then immediately filtered. For filtration, a filter paper listed as '"Eimer and Amend Best White FiUer Paper Xo. 15" has been employed. The filter paper mounted preferably in a small funnel having a long stem, is first moistened with a small amount of normal salt solution. Filtration at ordinary atmospheric pressure will usually be somewhat slow. By the use of a suction pump and a small amount of nega- tive pressure, the process of fihration is greatly facilitated. It has been my experience that the filtrate so obtained is clear and colored to only a slight extent bv the bile. IVADE W. OLIVER In lieu of filtration, centrifugilization may be employed. After the pneumococcus protein lias dissolved in the bile, the mixture is placed in a centrifuge tube and a small amount of cotton, with the fibers loosely united, is placed on the top of the fluid. Centrifugalization is commenced at low speed and the speed is gradually increased up to about 2,000 revolutions per minute. As the speed increases the cotton is pulled down to the bottom and assists appreciably in clearing the solution. Of the filtrate or centrifiigate, 0.3 to 0.5 cm. are now pipetted into each of three small tubes. To the first tube is added one drop of undiluted type 1 pneumococus antiserum, to the second tube is added one drop of undiluteally made in terminology by writers who call this condition hpyertrophic. I have had but one death due to this congenital anomaly and this in an unoperated infant, but I have seen material from several cases. The histologic picture is not hypertrophic but hyperplastic. The individual muscle fibers are not particularly increased in size, but there are more of them. Added to this is a varying amount of edema, and it is this edema that puts the finishing touch to the picture in the majority of the cases. Xo doubt there will always be differences of opinion between internists and surgeons as to a certain group of these cases, namely, the so-called spasm group. My own belief is that there is no such clinical entity as the"pyloric spasm of infancy." and that every case in which the symptoms are inter- mittent or remittent in character, is at least a mild case of true hyperplastic DUDLEY W. PALMER pyloric stenosis. This edema is a variable quantity producing by this varia- tion the symptoms of spasm the medical man so delights to treat with bella- donna veratrum-viridi and other drugs. There is just as much reason to say that the enlarged prostate, that in the "drunken spree" produces acute urinary retention, is due to a spasm. Similarly the obstruction is not a true stenosis of the lumen of the pyloric canal any more than of the urethra in l)rostatic hypertrophy. These obstructions are peri-ureteral and peri- pyloric. The above explanation is satisfactory for many of the observed symptoms such as the primary period of a few days or weeks without seri- ous vomiting. It puts all these cases with similar symptoms into one group with a material basis instead of forcing upon us the liecessity of evolving two groups to explain an otherwise simple condition. I want to call attention also to the fact that no reference was found in the literature to an instance in which the surgeon opened up a "spasm case" by mistake and found a "spasming pylorus." On the other hand, a sad number of cases were found in which the infant had been treated medi- cally for spasms until death from starvation occurred or the case became a grave surgical risk. Surgeons owe it to these helpless children to clarify the atmosphere and put this syndrome on a material rather than an elusive nervous-spasm-theory basis. Hutchinson's statement that when these in- fants get bad enough "they always turn the corner and get well" is not a safe rule for ])rocedure in view of what surgery now can offer. Before discussing the points in the operation, I shall say a few words with reference to the time the operation is indicated. Many patients who present rather acute symptoms do not need operation. Careful attention to the feeding, increasing the alkali intake, attention to the bowels, gastric lavage, and attention to air swallowing during nursing all are items of well known value to the good pediatrician. Watchfulness in these matters may tide the infant over a period when the edema is symptom-producing. Sauer, in July, 1918, was perhaps the first formally to report the use of paste feeding in congenital pyloric stenosis, though I had seen it used fre- quently before this in some cases in which I was interested. The paste feed- ing will unquestionably produce striking results in many cases, but I do not believe it will prove a cure all. Porter, in discussing the matter at the meeting of the American Medical Association, 1919, said : "He may use the thick feeding with an assurance that a proportion of cases will respond wtih complete restoration of digestive and nutritional function, and for stubborn ca.ses there is still left the brilliantly successful operative method of Fredet, which, used early enough, ougiit to obtain 100 per cent, of cures." This last clause, in my opinion, rec|uires and assumes a very close co-operation be- tween the i^ediatrician and the surgeon to insure justice to the child and to each other. A period of waiting may be desirable until iioinial dilatation of the canal occurs through physiologic use of the parts, and to jjcrmit an increase in tile muscular development of the stomach to propel the food along its course. RANSOM OFF MEMORIAL VOLUME While waiting it should be remembered that a child of two weeks weighing seven pounds is in far better condition than a child of two months weighing a pound or so more, and the younger infant can lose a pound with less risk. A child of about one month even moderatel)' well nourished, if it is holding its weight, can be treated paliatively for a couple of weeks while a little later a stationary weight may not warrant palliative treatment. The economic condition and intelligent co-operation of the mother also affect the decision with regard to treatment. Needless to say the child whose vomiting is ex- cessive, whose stools are without food content and who is steadily and rapidly losing weight, is a case for urgent surgery. Other evidences point to such urgency, such as loss of skin elasticity, sunken fontanelles. con- centrated or even suppressed urine, stupor and disappearing displays of hunger. Finally, it may be said that an operation is safer than the care of a poor ])ediatrician. e\en though the svmptoms are mild; it is also safer than the average unintelligent though well meaning treatment by the i)arents. The Fredet or so-called Ramstedt operation has undoubtedly lifted the surgery of congenital pyloric stenosis from an extremely hazardous group to the realm of comparatively safe surgery. Operative risks and operative mortality no longer incline one to delay ; on the contrary the operation can be advised to relieve the more mild symptoms and thus shorten and remove the worry of the parents. I have been interested in watching several patients for whom operation was refused, the condition not being urgent. These patients are still subject to attacks of gastric pain and distress with eructa- tions, and are an untold worry to the parents. Undoubtedly, however, some children are left without any symptoms after the original attack subsides. Practically every patient coming to the surgeon is in a marked state of acidosis and dehydration. I have adopted the principal thai a further delay Pa,jc .}.;,' DUDLEY IV. PALMER of twenty-four hours in which to prepare the infant is the wisest precedure. The preparation consists of alkahne gastric lavage, alkaline colon flushes (one or two) ; enemas of from 30 to 75 cc. every three hours and from 30 to 50 cc. of normal salt solution subcutaneously at three hour intervals, thus correcting a suppressed urinary secretion and improving the shrunken, dried up appearance. The subcutaneous injections may be used after operation for about twenty-four hours by which time nourishment is given freely. Feedings are continued up to the time of operation, in the hope that some part of the retained food may be passed on from the stomach ; a thorough gastric lavage is given just before operation. A number of cases of hyperplastic pyloric stenosis is associated with thymus enlargement, producing very embarassing symptoms, have occurred in my practice and I know of several "thymic deaths" following operations for pyloric stenosis in infants. Two years ago RansohofT reported such a case with postmortem finding in which death occurred about seven months after a perfect operative result. The associated enlarged thymus in my ex- perience has been more frequent than the incidence of enlarged thymus in the average infant, and the possibilities are so serious that a routine x-ray picture should be made of the chest before operation, and followed by treat- ment if the enlargement is found. You have all, no doubt, noticed the fre- quency of the references in the literature to sudden deaths following opera- tion for pyloric stenosis. It is scarcely necessary to call your attention to the fact that everything must be done in the operating room to conserve the body warmth and to expedite procedures. Cleansing the skin thoroughly with alcohol is sufficient. The extremities must be fastened to the table as otherwise their movements on the table may be disquieting. Ether is best for anesthesia; very little anesthetic is needed and a few drops of ether make a change from semi-con- sciousness to a too-deep anesthesia, from squirming and possible evisceration to suppressed respiration. I have not yet tried local anesthesia. A high right rectus incision extending well up to the costal border, of from 2.5 cm. to 3.75 cm. in length, is a great advantage, because the normally low hanging liver controls a tendency to evisceration; later the liver acts as a support should the integrity of the wound be threatened by the secretion of serum during the healing period. Two fingers are introduced and the liver is pushed up. By wiggling the fingers very much as Dr. C. H. Mayo sug- gested many years ago for finding an appendix, an olive shaped mass is palpated. This tumor is lifted to the surface and its most avascular area is incised longitudinally down to the mucosa. Because the shape of the infant's pyloric aperature on the duodenal side is very much like the cervix in a vagina, it is necessary to be extremely careful to avoid opening the sulcus or gutter surrounding the pylorus. Such a technical error adds greatly to the risk, since a plastic operation or a gastrojejunostomy then unfortun- ately becomes necessary. Frequently one cannot avoid cutting a small vein and as every drop of blood counts, it has seemed wise to control this with RANSOHOFF MEMORIAL VOLUME a hot tal) of gauze applied directly to the bleeding point for a few minutes ; this time is well spent, I believe, as catgut ligatures bite through this edema- tous, butter-like tissue. The incision can be extended well upon the stomach side of the pylorus without great risk, but it is much safer to refrain from attempting to cut the last few muscle fibers on the duodenal side. If a few fibers are left, spitting up or regurgitation of some food may occur; this is temporary and not alarming as the larger part of the food is retained and the explosive vomiting is controlled. The pyloric tumor is returned to place without further attention and the liver dropped down behind the incision. A layer suture of the abdominal wall, using a fine catgut (No. chromic catgut) with silk worm figure-of- eight fascial sutures has given the best results. No. 1 or No. 2 plain or chromic catgut is too large to be taken care of in the abdominal wall of these starved babies. Even with extreme detailed attention, a rather large per- centage of patients have a serum discharge that necessitates frequent dress- ings for a week or ten days. None of the wounds in my cases has had real pus form and none has failed to heal tightly without hernial tendencies. Patients with congenital hyperplastic pyloric stenosis 17 Patients operated upon 23 (85.18%) Fredet operations — 20 Gastro-enterostomy — 3 Patients not operated on 4 (14.81%) 1 died before operation could be done. 2 improved with palliative treatment (mild cases). 1 refused operation and has occasional symptoms. Males 79% First-born 58% Average age of patients at onset of symptoms 14 days Average age of patients when seen or at operation 02 days Average duration of symptoms 48 days Thymus enlargement proved to e.xist in patients operated on.... 26% Examination for palpable tumor positive 37% Examination for palpable tumor doubtful 18% E.xamination for palpable tumor negative 45% Waves visible 95% Patients of weight less than birth weight 61% BIBLIOGRAPHY 1. Dnwne?, W. .\.: Tlie operative treatment of pyloric obstruction in infants. Surs., Cynec. and Olist,. 1911.. .«ii. 251-257. 2. Holt, L. K.: Medical versus surgical treatment of pyloric stenosis in infancy. Joiir. :\m. Med. .\5sn., 191-4, Ixii, 2014-2019. 3. Hutchinson, R.: Concenital pyloric stenosis. Brit. Med. lour.. 1910, ii, 1021-102-t. 4. Le\yitt. VV. B., and Porter, L. : Pyloric obstruction in infants with muscular hypertrophy at the pylorus. Jour. Am. Med. .Assn., 1912, Ivii, 256-259. 5. McClanahan, H. M. : Duodenal ulcer; report of a case in which operation was followed by improvement. Jour. Am. .Med. .Assn., 1916, Ixvii, 1270-12;i. 6. Palmer, H. W.: Hyperplastic pyloric stenosis. .Ann. Surg., 1917. Ixvi. 428-435. 7. Porter, L. : A retrospect of fifteen years' experience in the treatment of hypertrophic ob- struction in infants. .Arch. Ped., 1919, x.xxvi, 385-397. 8. Ransahoff, J. I,., and Woolley. P. C: Operative cure of congenital pyloric stenosis. Jour. Am. Med. Assn., 1917, Ixvii, 1543-1544. 9. Sauer, h. W.: The use of thick farina in the treatment of pyloric stenosis. Arch. Ped„ 1918, XXXV. 385-400. 10. Scuddcr, C. L. : Stenosis of the pylorus in infancy. .\nn. Surg.. 1914, lix. 239-2.^7. Page m COMPLICATIONS AND END RESULTS OF BILE DUCT INFECTION.* J. Enw, riRRrxG. M.D., Cincinnati. It is generally ngreed that most of the di.seascs found within the bile passages are due to infection direct from the duodenum or infections car- ried by the blood and lymph streams to the liver. A considerable number of these infections come through the portal circulation, which is the great absorptive and drainage system of the intestinal tract. A previous typhoid is suggestive, a long history of constipation, obstipation, or hemorrhoids predisposes to bile passage infections. Fermentations and intoxications due to an increased bacterial growth in the intestinal tube give an increased work to the liver cells, consequently all the bacterial can not be burnt up in the liver ; some find their way into the bile passages and to the gall-bladder. Sir Berkley Monyhan has observed the frequent occurence of distentions with in the duodenum, infection of its contents, duodenum inflammation, duodenal ulcer and gall-stone in the same patient. Sir \\'illiam Lane ad- vanced a step farther. He states that duodenal distention is the result of delays to the passage of the fecal current. Infections then occur in the intestinal canal, inflammation, ulcer, and gall-stones are the result. Bacteria and their products being absorbed are carried by the blood and lymph streams to the liver, there many of them are destroyed, others pass out into the ducts, infecting the bile. The deposit of altered secretions of the Uver forms stone in the gall-bladder and bile passages. Infections, inflammation, distentions, altered secretions and the consequent lowered nutrition, with blood infections causes ulcers in the stomach and duodenum. The bacteria usually found in the bile passages are bacilli typhi isus, bacilli coli and the pus producers. Persons leading a sedentary life, wnnien past middle life, repeated pregnan- cies, dietary indiscretions and chronic infections in any of the abdominal organs predisposes to gall duct infections. The symptoms when stones are present and are passing through the bile passages are well known and need no comment. The History. — The early history is the most important in diagnosis before colic occurs. Occasionally hepatic colic seems to be the first evidence of gall duct trouble. However, on close questioning in such cases, you will bring out the story of a previous stomach trouble, bilious spells, fulness or distention preceding the attack of colic. When a patient comes to you with a history of long and continued dyspepsia, with nausea, fulness in the epigastrium, rightside bloating, constipation marked, occasional bilious at- tacks with temperature, severe pain in the right side running toward the middle line, pain temporarily relieved by vomiting (vomitus containing no RANSOHOFF MEMORIAL VOLUME lilood), a presumptive diagnosis of infection of tlie bile passages can be made. Examination of the stools during the acute attacks may also help in the diagnosis. There may be a temporary absence of bile in the stool due to stone obstruction or to the congestion and swelling of the mucosa of the ducts. Gall-stones are sometimes recovered from the stools. The above are the usual early symptoms of a persistent infection of the bile passages. When physical signs occur you are dealing with an end result of infection. The failure to elicit from the ])atient the symptoms of infection or stone in the bile passages is usually due to an incomplete questioning. These pa- tients will frequently give you the suggestion of gall-bladder disease in their history. You do not require jaundice, severe pain, a tumor mass, septic fever, itching, vomiting and clay-colored stools to make the diagnosis. These are the complications of infections. The time for permanent relief may be far past when one or more of these occur. They usually mean persistent obstructions of the cystic or common ducts by stone or adhesions ; peritonitis many times follows such obstructions ; some of the neglected cases of stone are sure to become cancerous. An added complication is that of disease of the pancreas. If abscess of perforation occurs and the patient survives, the adhesions following causes much distress from dypepsia, and many times mechanically obstruct the outflow of the bile. Perforations from stones or abscess may form fistulous tracts into the abdominal organs or lung. Ex- ternal openings discharging stones are on record. Intestinal obstruction from large stone ulcerated into the bowel are of frequent occurrence. The removal of gall-stones when they are all still confined to the gall- bladder is in the hands of competent surgeons now so safe from an operative standpoint, and so satisfactory in the relief of symptoms when early opera- tion is performed, that in all cases a diagnosis of infection or stones within the bile passages should mean early operation. If we would only appreciate the serious end results that follow continued infection, inflammation, gall- stones, colics, and attacks of obstructive jaundice, there would be less pepsin sold for "dyspepsia," so-called, and fewer attempts at lubrications and dis- solutions by the ingestion of "Italian olive oils," sal hepatica and natural waters (guaranteed to dissolve stone). Certain it is that they will not affect the condition. The temporary improvement sometimes noted under such treatment is due to the natural resistance of the tissues. The surgery of the bile passages should not be the surgery of the end results of infection, nor of the complications, rather we should early attack the infected gall-bladder (as surgeons now do the appendix), drain the gall-bladder early, relieve the infection, thereby obviating the complications which give such unsatisfactory results. Medical eiiforts at drainage through the ducts usually fail. I would here like to cite some of my unsatisfactory cases, unsatisfactory because of delay in coming to operation. Surgical skill will not and can not recompense for delays. In the hands of a coni- /. EDIV. PIRRUNG peteiit surgeon, the early drainage cases should all do well. The most skillful surgeon can not relieve many of the complications that arise from delay. Case I. — Mrs. H., aged seventy, blind for thirty years (cataracts) ; seen early in the fall of 1909; she was having severe cramps in the epigastrium. She gave a long history of dyspepsia, eructations, bloating, colics and con- stipation. Her abdomen was tender to the right of the middle line, a tumor about the size of an egg was felt under the edge of the ribs and down deep into the right hypochondrium. There was no jaundice and no enlargement of the liver. A diagnosis of cancer of the bile duct was made. In October, 1909, she developed obstructive symptoms, jaundice became marked and the liver greatly enlarged. About the end of October, 1909, the post-mortem was made, there was primary carcinoma of the common duct. In the center of the growth was a large stone lodged in the duct. There were numerous smaller stones packed in the liver ducts and in the gall-bladder. Case II. — Mrs. M., aged forty-four, seen May, 1909. She gave a long history of stomach trouble with repeated attacks of vomiting, biliousness, distention, colics, and during the past year was jaundiced on several occa- sions. Examination revealed tenderness over the liver and gall-bladder re- gions. A tumor mass was felt near to the head of the pancreas. A diagnosis of carcinoma of the bile ducts and head of the pancreas. No operation was attempted. July, 1909, post-mortem showed primary malignant disease in the common duct and at the head of the pancreas. There were secondary deposits in the liver. Stones were present in the common duct. Case III. — Mrs. F., aged twenty, seen April 27, 1911. Three days pre- vious she was taken with a sudden and severe pain in the epigastrium, violent vomiting ensued, the vomitus containing bile and Ijlood. Vomiting and pain were temporarily relieved by repeated hypodermics of morphia. Previously she had three such attacks and recovered, except between them a fulness within the abdomen and stomach trouble persisted. Examination : The upper adbominal muscles were very rigid, the liver dullness merged with a dullness of a mass which extended downward and inward towards the umbilicus. Her temperature was 100° F., pulse 90 ; vomiting was again becoming a prominent feature. This was the fourth day from onset. There was no jaundice. A diagnosis of perforated duodenal ulcer or gall-bladder was made and patient sent to hospital for an inmiediate operation. At operation there was found perforated and gangrenous gall- bladder. The mass was omentum and pus. There were no stones. The patient recovered after a very long and stormy convalescence. Her present condition is far from satisfactory because of adhesions about the pylorus and duodenum. Case I\'. — Geo. L., aged fifty-six, first examination August, 1906, diag- nosis was then made of gall-stones. Operation was advised but refused. Again seen during an attack in December, 1907, and in January, 1908, also RANSOHOFF MEMORIAL VOLUME September, 1909, and September, 1911, and again in August, 1912. He was the son-in-law of a physician. The doctor was not convinced that he Iiad gall-stones, hut rather believed he had "duodenal catarrh." The present attack of August, 1912. was ushered in by severe chills, high temperature, vomiting and jaundice. Diagnosis by his physician at this time was malaria. His .symptoms grew worse and on the third day an enormous mass was found in the right side. I was then called and diagnosed obstruction from gall-stones. He was removed to the hospital and an immediate operation per- formed. The gall-bladder contained one and a half pint of pus and bile, together with hundreds of stones. The cystic duct was obstructed by stone. A further examination failed to discover stones in the common or liver ducts. Drainage tubes were then placed in the gall-bladder and in the fossa under the gall bladder. His recovery was prompt but unsatisfactory. He has liad no return of colic or vomiting, but has a sense of uneasiness and stomach distress due to pylorus and Juodenal adhesions. His gall-bladder was drained for a period of six weeks. Case V. — Miss M. D., age thirty-seven, October. 1911. Onset of present illness was with severe and sudden pain in the right side accompanied by vomiting, jaundice, chills and fever. \\'hen I saw her she had been ill for five weeks, she had a large and tender gall-bladder, was deeply jaundiced; she said she had lost weight. Her past history was that of colics and dyspep- sia, such attacks extending over a period of thirteen years. Operation re- vealed many stones packed into the common duct. The gall-bladder was also filled with stones. The head of the pancreas was enlarged. Recovery from operation was prompt, all of the symptoms disappearing, and within three or four months she had gained twenty pounds. Six months later she had a recurrence of jaundice, chills, fever and vomiting. The jaundice was persistent. Being unable to determine whether stone or malignancy existed, I again explored the regions of the pancreas and gall-bladder. The head of the pancreas was much enlarged and obstructing the common duct. No stones were present. Malignancy was now certain. Nothing could be done. The patient failed to recover from the second operation, died on the tliird day following. Case \'l. — Mrs. L., aged forty-two. She had had years of stomach dis- tress, gall-stones, colic and dyspepsia. For the past eight years she had taken morphia for the relief of pain. In January, 1913, she decided that she would be operated upon. Examination showed an enlarged and tender gall-bladder, the tenderness extending toward the mid-line and into the region of the pylorus. Exploration was done under intravenous hedonal anesthesia. Malignancy of the duct was certain. No attempt was made to remove stones that were present. She is still alive; there is at the present lime an extension of the growth into the li\er. Three to five grains of morphia are required daily for licr relief. Her existence is miserable. /. EDIV. PIRRUNG T could add other cases to the above list, but the few herein reported will sutTice to make my point, that stasis of the bile within the bile pas- sages, infections, gall-stones and chronic pancreatitis are the forerunners of cancers of the organs. When cancer does not develop chronic invalidism or morphinism many times occur. Abscess and perforation are other of the complications. Diabetes of hepatic origin or, rather, diabetes following infections in the liver and ducts is not so uncommon. I have observed two cases of diabetes developing after gall-stones, in women who previously had had no sugar in their urine. Both of these cases refused operation. The infection in these two cases was of long standing. Five or six years of re- curring infection, jaundice and colics. These cases were taken from a series of operations upon the gall-bladder and bile ducts done within the past five yeafs. In Cases I and II of this report no operation was attempted. The cases were evident cancer at the time of my first examination. Case III shows the evil result of persistent infection causing perforation of the gall-bladder. There were no stones in this case, obstruction was caused by adhesions. Bacterial invasion of the mucosa and submocasa caused obstruction and perforation. The blood vomited in Case III may have come from a duodenal ulcer, mucous erosion occurring because of the infected bile flowing into the duodenum. Cases I, II, V and VI were cases of cancer developing from the chronic irritation of stone lodged in the ducts. In the cases operated. Case \ had a history of gall-bladder infection and stone extending over a period of nearly thir- teen years. Case VI had taken morphine for the relief of gall-stone colic for eight years. Such conditions should not be allowed to persist. Patients should be advised of the complications likely to arise. Operations performed early will obviate such complications, and it is the duty of the physician to warn the patient of the danger. At the close of a clinical lecture delivered at the Infirmary, New Castle- on-Tyne (British Medical Journal, January 3, 1914), Mr. Rutherford Mor- rison said : "Lives are still lost that could be saved and a delay not so dan- gerous often means prolonged convalescence and a dangerous illness which might have been averted by more accurate diagnosis and more prompt ac- tion. Improvement has been most marked in the more tragic conditions, such as some perforating gastric and duodenal ulcers, because symptoms are so serious and so pronounced that everyone concerned is convinced that something should be done without unnecessary delay. There are still too many appendix cases left to form abscess or to develop peritonitis before operation, and still more gall-stones left till serious complications such as abscess, common duct obstruction and cancer render operations serious and unsatisfactory." My plea then is to drain the gall-bladder early in infections. When gall- stone colic occurs there can be no permanent relief except that offered by operation. If ulcer of the duodenum is, as Monyhan and others believe it to be, due to infection, is it not reasonable to suppose that an infected bile RANSOHOFF MEMORIAL VOLUME continually pouring into the intestinal tract would add to the chances of ulcer in the duodenum? Cancer arising from chronic irritation is admitted by many observers. A stone lodged in the gall-bladder or ducts — more par- ticularly the ducts — is potentially a cause of cancer of those organs. Diabetes of hepatic organs, pancreatitis and some of the abscesses of the j)ancreas can lie prevented by the early drainage of an infected bile. rHE INFLUENCE OF BILE ON THE FAT-SPLITTING PROPERTIES OF PANCREATIC JUICE.* By B. K. Raciiford. M. D. Plate I. In the sjiring and sinner of last year, in the Berlin Physiological Lab- oratory, I made a stndy of the fat-splitting properties of pancreatic juice and read a paper on this subject before the physiological section of the Tenth International Medical Congress. The complete and more detailed ])resentation of this work is the object of this paper. The short pai)er on emulsion, apart from any interest or value that may attach to this portion of the paper itself, is of importance because of its bearing on the methods used in the study of pancreatic juice. I'.MULSIONS In 1870 E. V. l!rucke' announced the fact that when rancid oil- is shaken with a solution of sodium carbonate and certain other alkaline fluids an immediate emulsion results. He believed that the oil was broken into fine globules by the shaking and that the soap formed served to hold the eiuulsion by preventing the union of the oil globules. In 1878 Johannes Gad-* called attention to the fact that when oil contain- ing the i)roper percentage of fatty acid was placed on the surface of a car- bonate of sodium solution a beautiful spontaneous emulsion resulted, and from this he held that neither shaking nor any other outside mechanical force was necessary to the formation of an emulsion, but that the chemical force developed by the soap formation was of itself sufficient under favorable circumstances to break the oil drops into the finest emulsion globules. There is but little room for doubt, I think, that Gad is right in his opinion. In fact, the only question which might arise is whether the force developed by the soap formation is not a physical (Quincke) rather than a chemical one. Gad also believed with Brucke that the soap formed had much to do with holding the emulsion, and this proposition is, I think, now everywhere accepted, although opinions dififer widely as to the manner in which the soap acts in bringing about this result. I wish here to call attention to the method used by Gad in his study of spontaneous emulsion, since this method is the basis of the methods used by me in the study of the fat-splitting properties of pancreatic juice. A 54 % carbonate of sodium solution is placed in a series of watch- glasses, and drops of oil containing different percentages of fatty acid are gently placed, by means of a pipette, on the surface of the fluid in the watch- ^S,u'"l,KsL.idirVkr° WMe'ner" Aca'd. Xr'''VV'i5s*lns^^^ lid. Ixi, ii, Aliih., i,. ii.J. ■' V.y raiiciii ..il is meant oil containing fatty acid. Aicl.iv. fill .\iiat. u. Physiol., 1878, p. 181. RANSOHOn- MEMORIAL VOLUME glasses. The amount of spontaneous emulsion in the various glasses is care- fully noted and compared, and in this way one can readily ascertain the percentage of fatty acid required to give the best emulsion. It must, of course, be remembered in this connection, that the percentage of fatty acid required to give the maximum amount of spontaneous emulsion will \ary with other conditions: such as temperature, strength of soda solu- tion, etc.. and that therefore only experiments made under similar conditions can he compared. By this method Gad observed that under otherwise similar conditions a certain definite percentage of fatty acid must be present in oil to give the maximum amount of spontaneous emulsion. For example, he found that with a ^ % carbonate of sodium solution at room temperature, aboitt 5J.2 % of fatty acid was required, and that with increasing or diminish- ing per cents, of acid above or below 5^^ per cent, he got less and less emul- sion, until finally there was no emulsion at all. A \ery little more or less than 5y2 per cent, of acid gave an incomplete emulsion. He found, therefore, that ihe limits of good spontaneous emulsibility were not only constant but also quite narrow, and upon the^e important facts depends the value of his method. W'e have in Gad's method a simple and accurate means of determining the proper percentage of fatty acids for giving the best spontaneous emul- sion of any given oil under given conditions. After repeating the experiments of Gad and contirming his observations I devoted considerable time to the study of the influence of shaking and other outside mechanical means on the formation of emulsions. The oil used almost exclusively in my experiments was olive oil that had been neutralized by shaking for two hours with a saturated solution of barium hydrate at a temperature of 95° C. and then pipetted and filtered. Oil freshly prepared in this manner w-ill be found practically neutral, and the term neutral olive oil as used in this paper always refers to such oil. The stirring was done chiefly by currents of air carried from a blowing machine, into the liquids to be stirred h\ means of rubber tubing and glass rods. This method is not only more convenient but it has other advantages o\er the ordinary one of shaking the tube. My exj^eriments led me to the following conclu>ions : — 1st. Xo amount of stirring will give a permanent emulsion of either neutral olive oil or (if rancid olive oil in distilled water. ( P"rey^ found dif- ferently.) 2nd. Xo amount of stirring will give a permanent enmlsion with neu- tral olive oil and a Y^ % carbonate of sodium solution. 3d. Shaking rancid oil and a % % carbonate of sodium solution gives a good permanent emulsion, even though the oil contain a very small or a very large percentage of fatty acid. From the above observations we >ee that when the conditions for soaj) formation are present, shaking very nuicli widens ihe range of good cmul- 'Arcliiv, fill Anat. u. Physiol., IHl. ]). .!,'<-'. Pai/c J,ti2 B. K. RACHFORD sibility and promotes the formation of a good permanent emulsion, but when the conditions for soap formation are not present, the shaking has no influence whatever. In our study of emulsions we must remember that two things are nec- essary to the formation of a good permanent emulsion. 1st. The oil must be broken into very fine globules. 2nd. These globules must not only be prevented from running together, but they must also remain rather uniformly distributed throughout the liquid. Now since we know that soap and certain other materials, as albumen and mucilage, have the power of holding emulsions, it would seem an easy matter to make a mechanical emulsion by shaking neutral oil in a solution of soap, albumen or mucilage ; but such in truth is not the case. In my experiments with soap solution and neutral olive oil I found that in very heavy solutions of soap, by violent and prolonged stirring, I could get only an imperfect emulsion, one in which the oil globules were larger and more variable in size than those formed by spontaneous emulsion. These mechanical emulsions do not approach in perfection a physiological emulsion, such as milk ; and they can be formed only in very viscous liquids and with such great mechanical force as to place them beyond the pale of physiological importance. For the study, therefore, of the influence of stirring in the formation of good permanent emulsions, such as may have some physiological importance, we must return to the experiments already noted, where a moderate amount of stirring very much hastened and promoted the formation of good emul- sions when the conditions for soap formation were present. The influence of stirring under such circumstances may, I tiiink, be ex- plained as follows. When too little acid is present for the formation of a good spontaneous emulsion, the shaking or stirring simply favours the emul- sion by promoting soap formation. It breaks the oil into a number of small globules which are constantly presenting new surfaces to the surrounding alkaline fluid, thus enabling the soda to combine with all the fatty acid pres- ent, in the formation of soap, and the chemical force thus liberated by the soap formation becomes an important factor in the breaking of the oil dro]5s into the fine emulsion globubes, just as it does in pure spontaneous emulsion. When too much acid is present for good spontaneous emulsion, the pro- cess is brought to a stand-still by the formation of a heavy soap membrane between the oil drop and the alkaline fluid, thus preventing further soap formation. Under these conditions, shaking breaks the oil drop and con- sequently the soap membrane, thus constantly presenting new surfaces of oil to the surrounding alkaline fluid and in that way favouring soap for- mation and the resulting emulsification. We see, therefore, that while shak- ing may play a very important role in the formation of emulsions, its action is chiefly an indirect one, promoting emulsification by favouring soap forma- tion, and that the chemical force liberated by this jirocess 's the force most acti\e in breaking the oil dro])s into fine emulsion glolniles. From my experi- RANSOHOFF MEMORIAL VOLUME ments I formulate tlie following general law concerning the influence of stirring in the formation of emulsions. The amount of stirring required to give a good emulsion of oil in a 34 % carbonate of sodium solution will be in inverse proportion to the nearness with which the percentage of fatty acid in the oil approaches the proper percentage for giving the maximum amount of spontaneous emulsion. If the oil contains the exact percentage of fatty acid for giving the best s]5ontaneous emulsion, then the shaking will be superfluous, since a good emulsion will form without motion and no amount of shaking can improve it. If, on the other hand, the oil be entirely free from fatty acid, then, as we have seen, no amount of shaking will give a good emulsion. Between these two ex- tremes the above law applies, and shaking may contribute very largely to the formation of emulsions. In the application of the above principles we have a simple and convenient method of determining when an oil is practically free from fatty acid ; viz., shake it with a J4 % solution of carbonate of sodium, and if there be no fatty acid present, the mixture rapidly clears. By the same method we may tell when we ha\e fatty acid free from admixture with oil ; viz., shake the fatty acid with the soda solution, and if oil be present we will have more or less milky whiteness, which is char- acteristic of emulsions; but if no oil be present, we will have a simple cloudiness due to the insoluble soap formed. From all that has been said, it follows as a logical conclusion that the energy required to make an oil enuilsible will be in direct proportion to the stability of the oil molecule of the given oil. The more stable the oil molecule, the more energy required to split it into fatty acid and glycerine. It matters not whether the energy be in the form of heat or of organized ferments, bacteria, or of unorganized ferments as the fat-splitting ferment of the pancreas. During my experiments I found that heating neutral olive oil develoiied fatty acid and made it emulsible, and that if this heated oil be again neutral- ized it became non-emulsible, thus showing the emulsibility to be due to the acidity. I also found that the greater the heat and the longer applied, the more fatty acid was developed, so that boiled olive oil contained too much acid for good spontaneous emulsibility. It is an interesting fact that the acids freed by healing various oils seemed to have greater power in making them emulsible than a like quantity of oleic acid. This is especially true of castor oil. Castor oil is not made more emulsible by the addition of oleic acid, but after boiling, it may be emulsified by shaking it with sodium solution, but it never becomes spon- taneously emulsible; this latter fact Gad called attention to and thought it due to the viscosity of this oil. The stability of the castor oil molecule is shown by the great heat required to devclo]) sufficient fatty acid to give an emulsion. These facts seem to indicate that the fatty acids of an oil are the fatty acids best adapted for giving emulsibility to this particular oil. Page .iU.'i B. K. RACHFORD It is a physiological fact beyond dispute that the splitting of fats is a most important preliminary step in fat digestion. That the cooking of fats will develop in them fatty acid is therefore a fact of considerable physio- logical importance and one that, so far as I know, has not previously been noticed. As I have previously intimated, it is my belief that the chemical force developed by soap formation is the chief factor in the formation of all physiological emulsions, that it plays quite as important a role in the forma- tion of the emulsion as the soap does in holding it after it is formed. That soap has the property of holding emulsions is, I think, an undis- puted fact, but the manner in which the soap acts is a question concerning which there has been much difference of opinion. In explanation of this difficult ijrobleni I wish modestly to express my belief in a theory of emul- sions which is a modification of that offered by Gad. Gad believed that the fine globules of oil were coated as soon as formed, with insoluble soap particles which formed a protecting envelope that prevented the oil drops from running together. The modification which I offer is as follows: the chemical jMOcess of soap formation which breaks the oil into fine globules nuist develop considerable heat, this must necessarily have the eft'ect of bringing a certain amount of otherwise insoluble soap into solution. This heat will necessarily be local and felt chiefly just at the point where the soap is formed, and all the surrounding liquid will be cooler. The soap therefore which is brought into solution by the heat either is precipitated a moment later en coming in contact with coi>ler parts of the liquid, or it causes in- creased viscosity in the liquid. We may, therefore, say that the heat is developed, the soap formed and dissolved and the oil broken by the same force in the same place and at the same time. By this mechanism the oil globules are, as soon as formed, coated with a liquid soap which a moment later hardens about them in the form of soap membranes. These soap membranes at the moment of their forma- tion are not as capable of holding the globules as they are later, when, on cooling, they become more resisting. If this theory be true, it would follow that an appreciable length of time must elapse after the formation of an emulsion before it reaches its highest degree of stability. And this in fact I find to be true, that the emulsions can be more easily destroyed at the moment of their formation than later, and it is only in explanation of this and other facts that the above theory is offered. The following conclu- sions I draw from my experiments, and some of them are best explained by this theory. 1st. If bile be present an emulsion cannot form, although all the con- ditions otherwise favourable to its formation be present. This fact was pointed out by Gad, and he offered in explanation that the soap-dissolving properties of the bile prevented the formation of insoluble soap membranes, and that the unprotected oil globules ran together and came to the surface as free oil. RAXSOHOFF MFMORIAL VOLUME 2nd. If bile is added to an emulsion, the moment after it is formed the emulsion rapidly clears by creaining, but no free oil appears on the sur- face. Here it seems that the soap not in membranes is dissolved. This increases the specific gravity and diminishes the vicosity of the liquid, and as a result the soap-coated globules rise to the surface as cream; why it is that the soaj) in the membranes more quickly acquires the property of re- sisting the solvent action of bile than the soap not in membranes I cannot say. yet this seems the only explanation of the above phenomenon. 3rd. If bile be added to an emulsion some minutes after it has formed, it has no efTect in destroying the emulsion. The above propositions clearly indicate that an appreciable length of time must elapse after the formation of an emulsion before it reaches its highest degree of stability. 4th. One-tenth per cent, nitric and sulphuric acid and one-fifth per cent, lactic acid solutions rapidly destroy emulsions, the free oil running to the surface. Acids destroy emulsions by combining with the base of soaps and freeing the fatty acids ; the soap being thus destroyed, the liquid is much less viscous while the specific gravity is very little altered. The oil globules are therefore driven to the surface as cream, but if the acid be stronger, the soap in membrane is also destroyed, and free oil floats on the surface. The membrane soap is here found to be more resisting to soap destroyers than soap not in membranes. 5th. Hydrochloric acid has a much less destructi\e influence on emul- sions than has nitric or sulphric acid, and lactic acid has a less destructive influence than acetic. 6th. If sapo niedicatus^ be shaken in a Vv>% nitric or sulphuric acid solution the soda of the soap will combine with the nitric or sulphuric acid and fine globules of free fatty acid will rise to the surface. Sapo medicatus is more easily destroyed by nitric and sulphuric acids than it is by hydro- chloric acid. These facts strongly corroborate the opinion that acids destroy emulsions by destroying soaps. THE FAT-SPLITTING PROPERTIES OF PANCREATIC JUICE Since the publication" of Claude Bernard, physiologists have generally believed that pancreatic juice has the property of splitting neutral fats into fatty acids and glycerine. Claude Bernard himself believed that the pan- creatic juice had a two-fold action on fats. In the first place, he said that when neutral oil and pancreatic juice were shaken together an instanfaeous emulsion resulted. In the second place, that the prolonged action of pan- creatic juice on neutral oil would develop fatty acid. He did not in any way associate these two processes and believed them to be due to entirely different properties of the juice, the emulsion being an instantaneous process and the fat splitting occurring only after considerable time. .\nd these two processes are still described as separate and distinct properties of pancreatic "A soda soap made with olive oil acids. B. K. KACHFORD juice in some of our most recent text-books. But since the publications of Ilrucke and Gad. most German physiologists have associated these pro- cesses, believing that the emulsion was wholly due to the fatty acid which had been developed in the oil by the fat-splitting ferment and that the matter of inference from the works of Brucke, Gad and others, rather than from actual experiments with the juice itself. I have failed to find that any systematic work in this direction had been done with pancreatic juice since the days of Claude Bernard. Quite a number of attempts have been made, but the difficulties in obtaining a normal juice were so great that no exten- sive work has been done and no important fact added to our knowledge. But while almost no work has been done with the juice itself, an immense amount of work has been done with pancreatic extracts and infusions made from the gland. Physiologists have seemed to take for granted that, in studying the physiological properties of pancreatic juice, the juice itself offered no advantage over these extracts. In fact they seemed to believe from the great difficulty in obtaining a normal juice that the extracts were preferable, and our knowledge of the present day is based almost exclusively on experiments with the extracts, and but for the fact that they contain a fat-splitting ferment the time-honoured opinion of Claude Bernard would have carried but little weight. For these reasons, a systematic investigation into the fat-splitting properties of the pancreatic juice seemed to oiifer a fertile field for work. Although in the beginning tlie obstacle of obtaining normal juice in sufficient C|uantities to prosecute this investigation seemed insurmountable, yet I was fortunate enough to hit upon a method by which I could readily obtain from the rabbit a normal juice in sufficient quantities for experimental purposes. The operation for temporary pancreatic fistula in the rabbit is easily and quickly done as follows: Make an abdominal incision in the linea alba two and one half inches long. Bring the duodenum, which is readily found high up in the right hypochondriac region, through this open- ing, run down the gut to a point where the peritoneum binds it so closely that it will not come through the opening, and just at this point will be found the pancreatic duct as it runs through a leaf of the pancreas to the small intestine. Resect two inches of the intestine at this point, leaving its mesen- teric attachment, tie the cut ends of the intestine above and below and drop them in the cavity, bringing the resected portion through the adbominal wound. The abdominal wound is now partially closed by stitches, leaving only sufficient opening for the mesentery running to the resected gut. This resected gut is now laid open opposite the mesenteric attachment and spread out on the abdominal wall. The ends of the gut are clamped and its margins ])acked with absorbent cotton to prevent bleeding. Insert a small glass can- ula through the pancreatic papilla into the pancreatic duct and cover the exi)osed mucous membrane with absorbent cotton saturated with common salt solution. The flow of juice begins at once and continues from four to six hours. In this manner about 1 cc. of juice uniform and powerful in RAXSOHOFF MEMORIAL VOLUME physiological action may be collected. This operation is a modification of the Heindenhain permanent fistula operation" and has the advantage of being simple and uniformly successful. In my experiments I used the pancreatic juice of the rabbit, as it seemed quite impossible for me to obtain from the dog a normal juice in sufficient quantities for experimentation. The fat used was neutral olive oil. I worked for several weeks with very faulty methods before I hit upon the method which I afterwards used and which. I think, is admirably adapted to the study of the fat-splitting properties of pancreatic juice. The foundation-stone of the method is the spontaneous emulsion method of Gad. W'c have previously seen how by this method we may determine when an oil has the proper percentage of fatty acid to give the best spontaneous emulsion under certain given conditions. After having established the con- ditions under which one can get a good emulsion with a certain per cent (S'/O of fatty acid, it is evident that we can use this method for determining when an oil has this percentage of fatty acid, and since the completeness of the spontaneous emulsion will be in direct proportion to the nearness with which the quantity of fatty acid in the oil approaches this percentage, we have also a method of estimating the amount of increase of fatty acid in any oil by testing its spontaneous emulsibility from time to time. For ex- amjile. let us suppose that we have a neutral oil in which fatty acid begins to develop, and that this process slowly continues until all the oil is changed into fatty acid and glycerine. If the test of spontaneous emulsibility be applied to such an oil by placing a drop of it from time to time on carbonate of sodium solution, we get at first no emulsion at all, and then with the development of some fatty acid a slight emulsion, then more and more with increasing quantities of acid until the maximum emulsion is reached, which indicates that about five and a half per cent, of acid has been developed. The enuilsion then decreases with the further increase of acid until finally we get no spontaneous emulsion at all, which indicates about twelve per cent, of acid. Beyond this point the increase of acidity cannot be measured by spontaneous emulsion, but in this particular and under these circumstances the emulsion formed by shaking is of some value, for good emulsions may still be had in this way after too much acid has been developed for spon- taneous emulsion. But the greater the amount of acid the more shaking is required to give a good emulsion, until finally when all the oil has been changed into fatty acid and glycerine we get no emulsion at all, but only a cloudiness due to the insoluble soap formed. In this method we have a simple means of approximately estimating the increase of fatty acid in an oil and of determining when all the oil has been changed to acid and glycerine. This method is not used to determine the exact quantity of acid which an oil contains, bin is used rather to make a com[)arative estimate of the amount of acid in the same oil at difi:'ereni times and in different oils at the same time. 'Handbuch der Pliysiologit:, llcrrmaiin, BJ. v. Payc (68 B. K. RACHFORD This method is ajijihed to the study of the fat-splitting properties of pancreatic juice in the following manner. Arrange a series of watch-glasses containing a J4 % solution of carbonate of sodium. Take a small test tube of 2 cc. capacity and place in it Yi cc. of pancreatic juice and twice as much neutral olive oil. Shake the tube and allow the juice and oil to separate, then pipette a drop of oil from the surface and place it on ihe soda solution in watch-glass I. Again, shake the tube and allow the oil and juice to sepa- rate, then pipette as before, placing a drop of oil in watch-glass 2. Again shake and pipette as before, and repeat this process every three or four minutes until the experiment is completed. The beginning of the experiment and the time of each pipetting must be carefully noted. If the pipettings are three minutes apart, then the first drops of oil will have been exposed three minutes to the action of pancreatic juice, the second drop six minutes, the third drop nine minutes, and so on. By the amount of spontaneous emulsion occurring in these drops when placed on the soda solution one can com- paratively estimate the quantity of fatty acid they contain. For example, in an experiment such as I have just narrated one may find very little emul- sion in glass 1, more in 2, a fair emulsion in 3, good in 4, and the maximum in 5, and then the emulsion gradually decreases. By such experiments as this the fat-splitting properties of pancreatic juice can be beautifully dem- onstrated, and an idea formed of the rapidity of its action. There is a possible element of error in this method which had better be spoken of here. It would seem that the alkali of the pancreatic juice would combine with the fatty acids forming soap and in this way the oil would soon be emulsified in the juice itself and not separate after shaking. This would indeed be a serious drawback if it actually occurred, but in truth it does not occur until late in the experiment after we have obtained the information we sought by the spontaneous emulsion method. It is true that after a large quantity of acid has developed and by repeated shaking we get an emulsion of oil in the juice which somewhat interferes with the method. Although the sodium in the pancreatic juice exists in the form of a carbonate, it seems to be peculiarly associated with some other substance which interferes witli its combining with fatty acid in the formation of soaps. This may be illus- trated by the following interesting experiment. Place in a small test tube drawn out like a pipette equal quantities of pancreatic juice and neutral olive oil, 3/ cc. each. Shake the tube and set aside for twenty-four hours. .'\t the expiration of this time break the pipette point and allow the contents of the tube to escape slowly through the opening thus formed in the bottom . of the tube. The pancreatic juice, being at the bottom, is the first to escape, and it is clear and strongly alkaline ; then comes the oil which formed the upper layer, and it is strongly acid. Here we have a rancid oil and an alka- line fluid in contact for twenty-four hours with very little soap formation. This experiment clearly indicates that something interferes with the forma- tion of soap from the alkalies of the pancreatic juice. This is a plausible explanation of why the element of error caused by soap formation does RANSOHOFF MFMORIAL VOLUMF not iiUerfcri' with the iiractical applicatiiiii (if the method. But even the small element of error which is introduced hy soaji formation may be re- duced to a minimum hy usins:; small quantities of juice and three or four times as much oil, and in that way the Cjuantity of soda is greatly reduced and the action of the juice is but slightly retarded. This latter seems a strange statement, yet I have found in my experiments that within the limits named, the same quantity of juice splits large quantities of oil almost as readily as small. In passing, let me again call attention to the experiment above narrated as a simple and striking lecture experiment. The alkalinity of the juice and the acidity of the oil as it follows through the same open- ing may be demonstrated by litmus paper or solution. \\'ith these details as to method we are prepared to consider pancreatic juice and its action on neutral fats. 1st. The pancreatic juice of the rabbit is alkaline and remains so for some time after it is removed. On two occasions I tested juice that had stood exposed at room temperature for twenty-four hours and found it alkaline and physiologically active. Different specimens of pancreatic juice may vary in physiological activity. As a rule, the juice obtained from a fistula that has been acting several hours is not as active as juice from the same fistula obtained soon after the operation. 2nd. If pancreatic juice be shaken with neutral olive oil, the oil rapidly lakes on an acid reaction. That this acidity is due to fatty acid is show-n hy the facts that all the acid may be extracted with ether and the oil made emulsible by its presence. The gradual yet rapid development of fatty acid by the action of pancreatic juice on neutral olive oil may be beautifully demonstrated by pipetting drops of oil at intervals from the surface of a mixture of pancreatic juice and neutral olive oil and jilacing them on a J4 % solution of carbonate of sodium in a series of watch-glasses. Soon we have a slight emulsion, then more and more until the maximum is reached, then the amount of emulsion becomes less and less as too much fatty acid is developed, until finally we have no spontaneous emulsion at all. That an excess of fatty acid is the cause of the decrease and cessation of spontaneous emulsion may be demonstrated as follows. Take a drop of oil from a mixture of oil and pancreatic juice after it has passed the limits of spontaneous cmulsibility and mix it with neutral olive oil, and the mixture is spontan- eously emulsible. In one experiment, for example, I took one droj) of oil that had passed the stage of spontaneous emulsibility and mixed it with four drops of a neutral olive oil, and one drop of the mixture on soda solu- tion gave a beautiful spontaneous emulsion. Here one drop of the oil acted on by the juice contained sufficient fatty acid to make five drops of oil spontaneously emulsible, that is, to give five drops of oil about 5>^ % of fatty acid. The drop of oil acted on by the juice must therefore have contained about 30% of fatty acid and the time required to develop it was thirty-five minutes. Since 30/( of acid is so quickly develoi)ed, it seems Page !,-,0 B. K. RACHFORD a fair inference that the prolonged action of the juice would change all the oil fatty acid and glycerine, and such in fact is found to be the case. 3rd. All the oil is split into fatty acid and glycerine by from one to two hours' action of the pancreatic juice — time varies with the specimen of the juice. This may be shown by pipetting such fatty matter from the surface of the juice and shaking it with soda solution and no emulsion will result, simply a little clouding such as occurs when fatty acid is shaken with soda solution. But if one drop of this same fatty matter be mixed with si.x or eight drops of neutral olive oil, this mixture will, on being shaken with soda solution, give a good emulsion. This experiment is best performed by adding a small quantity of bile to the juice before adding the oil. The bile does not interfere with the fat-splitting action of the juice, but it does interfere with the formation of an emulsion, and for that reason the oil and juice continue to separate after shaking. 4th. The time required for pancreatic juice, acting in glass tubes at room temperature, to develop sufficient fatty acid (5>^%) in neutral olive oil to give the maximum spontaneous emulsion varies with different spec- imens of the juice and with the amount of shaking to which the juice and oil are subjected, but the average time as taken from my experiments was twenty minutes. In very active specimens of the juice it occurred as early as seven minutes, and in very poor specimens as late as sixty minutes. I also found that the juice did not act more rapidly in a basin of intestine than in the test tubes. In these experiments the resected intestine containing the pancreatic papilla was held by a fenestrated quadrilateral clamp made for the purpose, and into the basin of the intestine thus formed the pancreatic juice would ooze. Neutral olive oil was dropped into this basin and mixed with the pancreatic juice, and this oil did not become spontaneously emul- sible more quickly than the oil in the test tubes, but the conditions here are also far from resembling those occurring in the normal duodenum, and the average rate of fat-splitting as estabhshed by these experiments is probably considerably below the rate at which fats are split in the duodenum. It is probable that the time required by the most active juice p.iore nearly rep- resents the rapidity of action of pancreatic juice in the duodenum. 5th. The action of pancreatic juice on most of the fats is rapid and complete. Castor oil is a notable exception to this rule, as only a very small quan- tity of acid is developed in it Ijy the action of pancreatic juice for five hours at 2>7° C. Castor oil is therefore practically indigestible and this may in part account for its cathartic action. Pancreatic juice acts slowly on fats which have a melting point above body temperature, but it is an interesting physiological fact that their solidity at body temperature does not prevent their being split. Spermaceti for exam- ple, the melting point of which is above 38° C, is slowly split by the action of the pancreatic juice. RANSOHOFF MEMORIAL VOLUME 6th. As T have previously said, the pancreatic juice of the rabbit and neutral olive oil when shaken together show very slight tendency to the formation of an emulsion, and it is only after considerable acid has de- veloped that repeated shaking will give a mixture resembling an imperfect emulsion. But if we mix and shake at intervals one part of neutral olive oil and one part of pancreatic juice for about fifteen minutes, and then add six parts of soda solution, we get at once an apparently good emulsion. This emulsion does not remain good ; it always in the course of an hour or two clears by creaming, when the whole mixture will be found to have a strong acid reaction due to the large quantity of fatty acid developed. What- ever may be the explanation of the clearing of this pancreatic emulsion, the fact remains that an emulsion will form in the presence of pancreatic juice if carlionatc of sodium solution be added, but it does not remain permanent. 7lh. A permanent pancreatic emulsion may be formed by pipetting the oil from the surface of a tube containing oil and juice and shaking it with the carbonate of sodium .solution. The emulsion formed in this way remains very much the same for an indefinite length of time. In this experiment the oil is made emulsible by the action of the juice and is then separated from it and emulsified with the soda solution; the emulsion itself contains no ])ancreatic juice and therefore does not clear. This permanent pancreatic emulsion reacts to emulsion destroying agents and soap dissolvers very like a fatty acid emulsion made with rancid oil and sodium solution. For exam- ple, it is not destroyed by the addition of bile or fatty acids, but is destroyed by mineral acids, resisting hydrochloric better than nitric and sulphuric acids. The pancreatic emulsion also resembles the simple rancid oil emul- sion in that an appreciable length of time must elapse after its formation before it reaches its greatest degree of stability. This may be demonstrated by adding bile in excess immediately after the formation of the emulsion, when it destroys the emulsion by creaming, but if the bile be added later no such eiifect is produced. It also resembles the rancid oil emulsion in that it cannot form at all in the presence of bile. The most important application of the method I have described is in obtaining comparative information concerning the fat-splitting properties of pancreatic juice. This application of the method may best be explained by detailing an experiment inquiring into the difference in the rapidity of action of pancreatic juice at room (18° C.) and at body teinperature (37°). Arrange two rows of watch-glasses containing a J4 % carbonate of so- dium solution. Take two small test tubes, ]/i c.c. of the same pancreatic juice in each, and to each tube add Yi c.c. of neutral olive oil. Shake both tubes equally and place one of them (A) in a sand bath kept in an oven at 2i7° C. and leave the other (B) at room temperature. At the expiration of three minutes pipette a drop of oil from A and place it in watch-glass 1. row 1 ; then as quickly as possible, with a clean pipette, take a drop from ]'. and place it in watch-glass 1, row 2. Both tubes are shaken and replaced and at the expiration of three minutes a drop is again i>ii)etted from the sur- Pa,jc .}7i A'. RACHFORD face of each. That from A is placed in row 1, that from B in row 2. This process is repeated again and again to the end of the experiment. At the close of the experiment it will be found that the emulsion occurs almost twice as quickly in row 1 as in row 2. The three-minute drop of oil from A gives as good an emulsion as the six-minute drop of oil from B, and the nine-minute drop of oil from A gives the same emulsion as the eighteen- minule drop of oil from B. Since these tubes were, apart from the tempera- ture, treated as nearly alike as possible, we infer that pancreatic juice acts about twice as rapidly at 37° C. as it does at 18° C. The average ratio of in- creased rapidity of action, taken from my experiments, was as one to one and eight-tenths. Whatever objections may be urged against the absolute accuracy of the figures obtained by this method, the same do not apply to the comparative accuracy of these figures. Even though we may not be able by this method to estimate the amount of acid produced by pancreatic juice in nine min- utes acting at 37° C, we do know by this method, whatever this amount may be, that it requires one and eight-tenths times as long for pancreatic juice to produce the same amount at 18° C. In comparative experiments such as this it is not necessary nor practicable to have an equal length of time between the pipettings, but it is important that the tubes should be shaken at as nearly the same time and pipetted at as nearly the same time as pos- sible, so that the oil drops to be compared by spontaneous emulsibility may have been exposed to the action of the juice for the same length of time, thus establishing the comparative accuracy of the results. The great value and wide appliction of this method is seen in the study of the influence of bile and other agents on the fat-splitting action of i)an- creatic juice. Bile alone does not split fats. This seems a well established ])hysiological fact, which may be confirmed by shaking neutral olive oil and bile in a test- tube and pipetting the oil at intervals to the surface of a carbonate of sodium solution as in previous pancreatic experiments, when it will be found that oil shaken with bile for twenty-four hours does not become emulsible. The value of this method is here most conspicuous as the emulsibility of the oil could not be tested in the presence of the bile, because the bile would pre- vent an emulsion even if the fatty acid had been developed. But in this method the oil is separated from the bile after they have been in contact twenty-four hours and its emulsibility tested, and in this point lies the great value and wide application of the method, since the very agents, such as bile and hydrochloric acid, which have the greatest influence on the fat- splitting action of pancreatic juice, are the agents which interfere with the formation of emulsions. Fresh rabbit bile removed from the gall bladder was used in all my experiments. In every comparative experiment the pancreatic juice which had been collected in a single tube was divided into two, three or four equal ])arts RANSOM OFF MEMORIAL VOLUME according to the number of tubes used in the experiment. The bile was also^ shaken and divided just previous to the experiment. In this way I could be reasonably sure that I was working with the same bile and same pan- creatic juice in all the tubes. P.y the methods described I reached the following conclusions. 1st. An equal amount of fresh rabbit's bile will, on being added to ral)hit's pancreatic juice, greatly hasten its fat-splitting action in the ratio of three and one-fifth to one. In experiments of this kind, tube A contains ,'3 cc. of pancreatic juice and J/2 cc. of neutral olive oil, and tube B contains 3<5 cc. pancreatic juice and Yi cc. bile and ^-5 cc. of neutral olive oil. These tubes are treated alike and the emulsibility of the oil is tested from time to time as previously described. In this way the comparative rapidity with which fatty acid is developed in the oils may be determined. It is evident that in every experiment we can have two sets of figures from which to make our average, viz. the time required for the beginning and the time required for the maximum of spontaneous emulsion. In my general averages I have used both sets of figures, striking an average between them. 2nd. An equal quantity of a >4% solution of hydrochloric acid will, on being added to pancreatic juice, retard its fat-splitting action in the ratio of two-thirds to one. 3rd. A mixture of equal quantities of bile and a %% hydrochloric acid solution will, on being added to pancreatic juice, greatly hasten its fat-split- ting action in the ratio of four to one. The bile not only neutralizes the retarding influence of the hydrochloric acid on the fat-splitting properties of the juice, but it really acts more powerfully in hastening the action of the juice when in the presence of this acid than it does when acting alone. The contents of a series of tubes will best explain the class of experiments upon which this statement is based. Tube A contains Y cc. pancreatic juice and % cc. neutral olive oil. Tube P) contains l-\i cc. of pancreatic juice, ^ cc. of bile and % cc. neutral olive oil. Tube C contains '/j cc. of pancreatic juice, Vo cc. of bile, \{; CC. of a J4 % hydrochloric acid solution, and % cc. of neutral olive oil. Three rows of watch-glasses containing soda solution having been ar- ranged for the reception of the oil drops, the tubes are now shaken and pipetted as in previous experiments and the time and the result are carefully noted. In row 1 containing the oil drop from A, the emulsion begins in eight minutes, and reaches the maximum in twenty minutes. In row 2 con- taining the oil from B, the emulsion begins in two and a half minutes and reaches the maximum in six and a quarter minutes. In row 3 containing the oil drop from C, the emulsion begins in two minutes and reaches the maxinuini in five minutes. These figures are the averages of a number of exiierimcnts. 4lh. If an e(|ual quantity of a 3% solution of glycocholate of soda be mixed with pancreatic juice it hastens the fat-splitting action of the juice in llie ratio of two and one-fifth to one. B. K. RACHFORD 5th. A mixture of e(|ual (|uantilics of a i^'/< solution of glycocholate of soda and a '4% solution of liydrochloric acid will, on being added in equal quantities to pancreatic juice, hasten its fat-splitting action in the ratio of two and one-third to one. 'I'he glycocholate of soda solution, like the bile, not only neutralized the retarding influence of hydrochloric acid on the fat-splitting action of the juice, but it really acts more powerfully in hastening the action of the juice when in the presence of the acid than it does when acting alone. It must also be noted that the glycocholate of soda does not act as powerfully in hastening the fat-splitting action of the juice as the bile does. In the pres- ence of bile the juice acts three and one-fifth times as rapidly as it does alone, and in the presence of a three per cent, solution of glycocholate of soda it acts two and a fifth times as rapidly. In the presence of bile and hy- drochloric acid it acts four times as rapidly, and in the presence of glyco- cholate of soda and hydrochloric acid it acts two and four-fifths as rapidly. From this I infer that this property of the bile is chiefly but not wholly due to the glycocholate of soda it contains. The class of experiments by which these conclusions were reached is illustrated in Plate I, which is in part reproduced from a photograph. 6th. If one part of pancreatic juice be diluted with five parts of a y^ % carbonate of sodium solution its fat-splitting properties will be greatly retarded — in the ratio of one to eight — and further dilution with soda solu- tion gives greater retardation, this property of the juice being practically destroyed when it is ten times diluted with this strength of soda solution. That this retarding influence is due to the soda, and not to the dilution, is shown by the fact that if pancreatic juice be diluted with five parts of dis- tilled water, its fat-splitting action is very slightly, if at all. retarded. The retarding influence of soda solution may be shown by the same kind of experiments used to show the influence of bile, hydrochloric acid etc. on the fat-splitting properties of pancreatic juice. But it seems possible that there might be considerable cause of error in this class of experiments, because of the presence of soda solution in one of the tubes. In an exper- iment of this kind, for example, one tube contains Vi cc. of pancreatic juice and % cc. of neutral olive oil, the other contains in addition to the same quantity of juice and oil % cc. of soda solution. In pipetting oil from the surface of two such tubes to test its spontaneous emulsibility, will not the result be greatly vitiated by the soda solution in one of the tubes, neutralizing the fatty acid as soon as formed? Theoretically this would seem to be an important source of error, but practically it is not of very great importance, since the results obtained by this method correspond closely to those obtained by another method which has not this source of error. The following experiment will illustrate this method. Take two small glass tubes. In one place Yi cc. of pancreatic juice and ^3 cc. of neutral olive oil. Shake four or five minutes and add % cc. of soda solution and an immediate emulsion will result. To the other tube add Yi cc. pancreatic juice and >fi cc. of neutral Page 7,75 RANSOM OFF MEMORIAL VOLUME olive oil and % cc. of soda solution. Shake, and the emulsion will not appear for thirty or thirty-five minutes. In the first tube, the pancreatic juice acting alone on the neutral oil produced enough acid in four or five minutes to make the oil emulsible on shaking it with the soda solution. L!ut in the tube 2, the presence of the soda solution retarded the action of the juice so that it required thirty minutes to produce suft:cient fatty acid to give an emulsion. Carbonate of soda solution therefore retards the fat-splitting action of pancreatic juice in the ratio above given. In the accompanying diagram I have taken a line twenty millimetres long to represent the working power of pancreatic juice acting alone at room temperature. The other lines represent the comparative working power of pancreatic juice under the conditions named, and were obtained from averaging all my experiments. DL\GRAM SHOWING THE INFLUENCE OF BILE .\XD OTHER .\GENTS ON THE F.'SiT-SPLITTlNG PROPERTIES OF PANCRE.A'I'IC JUICE Pancreatic juice at 18'^C. 20 Mil. I Pancreatic juice at 37°C. 36 Mil. ?.-, Pancreatic juice at 18° C. and HCl. 13 Mil. % Pancreatic juice at 18° C. and glycocholate of soda. 44 Mil. Vr, Pancreatic juice at 18° C. and gl\ 56 Mil. Pancreatic juice at 18° C. and bil 64 Mil. ^^^^^^->- Pancreatic juice at 18° C. and bile and HCl. 80 Mil. ^—^—.-...^^^^-^^^— The above diagram and accompanying figures are offered as the clearest and briefest manner of expressing the difference in the rapidity of action of the various mixtures. It is not even hoped that these figures are abso- lutely correct, but it is my belief that relatively they are approximately cor- rect, and therefore have an all important bearing on the pancreatic digestion of fats. \\'e may summarize. (1) Pancreatic juice can. acting alone, do a certain piece of work in .V minutes, viz. develop in neutral olive oil a sufficient quantity of fatty acid to give the best spontaneous emulsion. (2) Pancreatic juice acting in the presence of five parts oi a %% carbonate of soda solution will require 8.r minutes to do the same work, and in the presence of ten parts of the ^.ame solution its action will be almost destroved. B. K. RACHFORD (3) Pancreatic juice acting in the presence of an equal quantity of a ,'4% solution of hydrochloric acid will require %x minutes to do the same work. (4) Pancreatic juice acting in the presence of an et|ual (|uantity of mixture of bile and a %% hydrochloric acid solution will require only y^.v minutes to do the same work. Froiu the last two propositions it would follow that, if bile be added to pancreatic juice which is acting in the presence of hydrochloric acid, the fat-s|ilitting action of the juice will be hastened as % to Y^ or as six to one, and reversely, that if the bile be withdrawn or cut off from pancreatic juice which has previously been acting in the presence of both bile and hydro- chloric acid, the fat-splitting properties of the juice will be retarded as six to one. .\PI'LIC.\T10.\ f)l' THliSH PRIXCIJ'LES TO THl': IXTl^STIX.XL DICHSTIUX OF F.ATS It is needless to say that my experiments were planned with the idea of placing pancreatic juice under conditions as nearly as possible resembling those under which it acts in the intestine. The influence of a ^4 % solution of HCl was studied because of the presence of this acid in the duodenum where the pancreatic juice comes in contact with the fats. ' The influence of bile and of a mixture of bile and hydrochloric acid were studied for the same reason. The influence of dilution with a ^4 % solution of carbonate of sodium was studied because it was thought, that, as the pancreatic juice passed downward into the small intestine, it might be subjected to some such influence, since the succus entericus contained this percentage of carbonate of soda. 'J'he conclusions therefore to which I have arrived must, if true, have a very important bearing in the explanation of the intestinal digestion of fats. I infer from my experiments that in the duodenum the mixture of bile tnd hydrochloric acid furnishes the best known conditions for ex- pediting the fat-splitting action of pancreatic juice, and the cutting olif of the bile would retard the fat-splitting action of the juice six times. It may also be of some physiological importance to note that the agents bile and HCl which expedite the fat-s|)litting absolutely preclude the formation of emulsions. The duodenum therefore olTers the most favourable conditions for the splitting of the fats and the most unfavourable for their emulsifica- tion. In the jejunum and ileum these conditions seem to be exactly reversed. The intestinal juice containing, as it does 34 %' of carbonate of soda, would not only furnish the conditions for the spontaneous emulsification of the rancid fats, but would also retard the fat-splitting action of the pancreatic juice. I do not wish to express the belief that intestinal juice jilays just such a role as this in the intestinal digestions of fats, but only oiTcr it as a deduction from te^t lube experiments, thinking it may lia\e some physio- lo<>ica! bcarint'. RANSOHOFF MEMORIAL VOLUME From my experiments I infer that pancreatic juice must act very rapidly under the favourable conditions found in the duodenum. In some of my experiments at room temperature, good specimens of pancreatic juice aided by the presence of bile and hydrochloric acid produced, in neutral olive oil, 5K' % of fatty acid in two minutes. At body temperature this work would have been accomplished in one minute, and under tlie favourable conditions ofifered by the duodenum it would probably have been done in even less time. This rapidity of action of pancreatic juice is of great physiological im- portance since it is evident that at this rate, all the fats would be split into fatty acid. and glycerine in the time required for intestinal digestion, unless this action of the juice was checked or retarded in some manner. IMPORTAXCE OF BILE IX THE IXTESTIXAL DIGESTIOX OF FATS The various conditions which have an influence on the intestinal diges- tion of fats have been developed by natural selection, and so far as we know they are the best for the purposes they serve. The comparative im- mobility of the duodenum, its close attachment to the head of the pancreas, its horse-shoe shape, all, no doubt, have an influence on the rate of passage of food stufTs. This rate, which is chiefly controlled by these and other ana- tomical conditions, was established to accord with normal digestive functions, and by this mechanism the fats are exposed to the action of pancreatic juice just long enough to allow for whatever action that juice may have in fat digestion. Let us suppose that under normal conditions the fats are exposed in the duodenum to the action of pancreatic juice for x minutes, and that this time is just sufficient to allow for whatever fat-splitting is nec- essary at this point. Now if the bile be cut oiT, the rate of passage of the food stuffs, which is chiefly controlled by anatomical conditions, remaining the same, the fat would still be exposed to the action of the juice for only X minutes. But since in the absence of the bile the pancreatic juice is able to accomplish only 'i, of the fat splitting which it normally does it would follow that the fats would pass with only lis of the amount of splitting that normally occurs, and since the splitting of the fat is, as recognized by all physiologists, a necessary preliminary step in fat digestion, it would follow that the fats would pass in great part undigested. This gives to bile a most important and definite position among the juices which assit in fat digestion, since we have here pointed out at least one of the ways in which it exerts its wonderful influence in fat digestion. Physiologists have been led to believe through much clinical and experimental** evidence that the bile was necessary to fat digestion. How and where it acted has been one of the greatest of phy- siological mysteries. The experiments of W'estinghausen" seemed to show that bile promoted the passage of the fats through membranes, and this was thought by some i)hysiologists to have a bearing on the absorption of fats. SOf special interest are the recent experiments of A. Dastre in tlic Arch, de Pliysiologie et PatlioloRie. Paris. "Archiv. fiir Anal. u. Phys., lf<73. B. K. RACHFORD I'.ul since thf ])ul)licati<)n of Groeper'" denying that bile had any such action we have been quite a1> much at sea as ever in explaining the action of bile in fat digestion. I wish to thank Prof. Gad for his kindness and advice during the prose- cution of these studies. ADHERENT HERNIAS OF THE LARGE INTESTINE.* By J. Louis Ransohokf. M. D. Cincinnati. Sliding hernia of the sigmoid is a subject whicli as a rule does not receive the attention it merits. In most text-books on surgery, even in some of the treatises on hernia, it is barely mentioned. Though uncommon, it is one of the most important forms of hernia, its importance lying in its recognition during operation. If unrecognized, proper operative steps cannot be insti- tuted, and the viability of the bowel may be jeopardized. Since the first accurate description by Scarpa in 1812, it has been vari- ously known as adherent hernia of the large intestine, hernia with incom- plete sac or sliding hernia, the hernie par glissmentc of French authors. As I hope to show, the only proper designation is adh.erent hernia of the large intestine, the other terms being misnomers, based on faulty conception of pathogenesis. The most widely accepted theory is that this form of hernia occurs by the sliding of the gut on the posterior peritoneum. Before going further it is essential to describe the appearance of the unreduced hernia in the opened sac. The contents of the sac are either caecum and ascending colon in right hernias, or ileopelvic colon (commonly called sigmoid) in left her- nias; very rarely the transverse colon. The sac, well formed and complete on its anterior aspect, is seemingly deficient behind, the bowel being tightly adherent to, and apparently incorporated in, the posterior wall of the sac; hence the designation, hernia with incomplete sac. Fig. 1 shows this con- dition in sagittal section, Fig. 2 in cross section. If the incision in the sac is carried through the internal ring into the abdominal cavity, it will be seen that the adhesions of the gut to the posterior surface of the sac are continu- ous with the mesosigmoid, or with the normal reflection of the peritoneum from the bowel to the posterior abdominal wall. An attempt to reduce the bowel will be unsuccessful until it is separated from the posterior wall of the sac by sharp dissection or without reducing sac and gut together. Above all. it is noteworthy that the adhesions between gut and sac wall show no evidence of being inflammatory, but resemble what they really are, the usual adhesions of the large intestine to the posterior peritoneum (Fig. 7). PATHOGENKSIS. In attempting to elucidate the various theories. 1 siiall speak principally of adherent hernia of the sigmoid, as what pertains to hernias of the sig- moid on the left side may be applied to hernias of the caecum on the right. I shall first consider the commonly accepted theory, that these hernias are due to the sliding of the posterior peritoneum on the underlying cellular tissue, the peritoneum sliding into the internal ring, carrying with it the attached loop of large bowel. This theory apjiears untenalile, and rightly so, * From tlie .\nr.als of Surgery, .\ugu>l, 191_'. Page iSO /. LOUIS RANSOHOFF. Figure 1. Sagittal section of adherent hernia of large intestine, showing adhesions between mesentery, gut and posterior wall of sac. Figure 2. Cross section of large intestine, show- ing adhesions between mesentery, gut and sac wall, with nutrient vessels in the adherent mesentery. Cross section through abdomen at third lumbar vertcljra, looking toward diaphragm, showing mesentery of ascending and descending colon adherent to posterior abdom- inal wall. as it i.s based upon unsound mechanical princi])les. The iliopelvic colon or sigmoid is, in pari, normally attached to the posterior peritoneum at the level of the left sacro-iliac synchondrosis, by a broad fold of peritoneum, which appears deficient on the posterior aspect of the gut. That is, the posterior surface of the bowel is apparently in direct contact with the refo- peritoneal cellular tissue of the ileopelvic fossa. In a certain number of cases, however, the attachment of the ileopelvic colon lies at a lower level and the anterior leaf of its peritoneal covering is reflected to the anterior abdominal wall, just above Poupart's ligament, the posterior leaf to the pos- terior abdominal wall just above the internal ring. This brings the posterior uncovered surface of the bowel in direct contact with the internal ring, also uncovered by peritoneinii, as its peritoneal covering has been dislocated to the anterior abdominal wall. .\ny sudden increase in intra-abdominal pres- sure or jjrolonged increase, as due to straining at stool, is sufficient to force the knuckle of bowel through the unprotected ring and into the canal. The RANSOHOFF MEMORIAL VOLUME Figure 4. Figure 5. Figure 4. Alimentary tract of embryo of six weeks, showing rudiiiiciils of the two mesenteric systems (after Hertwig). Figure 5. Embryo of eight weeks, showing large intestine with free mesentery outlining the abdomen. r,gur<. 6 ving the adherence of the entire ascending and desccndiny ns beginning at the hepatic and splenic flexures. continu.incf of presMire forces the gut. tlraggiiig the peritoneum behind it, furtlier along the canal into the scrotum. This low position of the sigmoid is supposedly due to the downward dislocation of the peritoneum lining the lower portion of the abdomen. This dislocation is either congenital or has been caused by increased intra-abdominal pressure. It is presumed that the Ijosterior peritoneum has become loosened from its underlying supporting cellular tissue. This theory, accepted by Ranzi, Scarpa, Wier, Stoney. and many others, is utterly fallacious. Even in the opened abdomen, it is no easy task to strip the peritoneum front the abdominal wall, so close is its adherence; in addition to this, any increase in intra-abdominal pressure only serves to apply the parietal peritoneum more closely to the abdominal wall. If this form of hernia occurred by sliding of the peritoneum on the posterior abdominal wall, there would be a dislocation of the entire posterior /. LOUIS RANSOM OFF. peritoneum \\ ith the attached gut ; whereas, the splenic flexure on the one hand, and the hepatic flexure on the other, are invariably found in their normal antomical positions. It is true, that Tuffier has reported a case of enormous hernia of the descending colon, where the kidney was dislocated. This, however, was probably due to a dragging of the inferior mesenteric artery on the aorta and the dislocation of the aorta and through it a dislo- cation of th^ kidney. Again, if this form of hernia occurred by sliding, there would be from the moment of occurrence difficulty in reduction; whereas, in nearly all cases the history points to the hernia having become irreducible only after months or even years. Rut most convincing of all are the few cases in which, without visceral transposition, the Cfecum has been found adherent in left-sided hernias and Figure 7. Oraning from life, slinwiiig tlie sigmoid aillitTcnl in tlie opened sac. the sigmoid in the right hernias. By the utmost stretch of imagination tiiere can be no discussion on this point ; the peritoneum on the left side cannot .slide into the right inguinal canal, nor vice versa. Furthermore, it is almost axiomatic that the .f/»r qua non of the development of a hernia of an intes- tinal coil is the mobility of that coil. If a loop of intestine is found fixed in a hernial sac. it is conclusive proof that before the formation of the hernia the loop was mobile. The sigmoid does not rest on the cellular tissue of the posterior abdominal wall, but is separated from it by a triplicate layer of fused peritoneum. First the posterior peritoneum itself, second and third the double layer of adherent mesentery through which the nutrient vessels of the gut ])ass (Fig. 4). This same rclationshi]) exists between the sac wall and the adherent intestinal coil (Figs. 1 and 2). This fused peritoneum, called b)- the French the fascia d'accolcntcnt, fixes the attached portion of Fagc 'iS.i RAh'SOHOFF MEMORIAL VOLUME the sigmoid and caecum firmly to the posterior abdominal wall, and itself prevents any possibility of sliding or dislocation. An ingenious, though untenable, theory has been advanced by Lockwood, who claims that before the descent of the testes the right testicle lies in close relationship to the crecum, the left to the sigmoid flexure. Lockwood sup- ])oses that an abnormal adhesion develops between the caecum or sigmoid on the one hand and the right or left testicle on the other. The testicle in its passage downward through the internal ring pulls on the caecum or sig- moid, as the case may be, and dislocates it downward to the region of the internal ring, where any slight increase in pressure is sufficient to force the gut into the inguinal canal. The untenability of this theory can be appre- ciated when it is realized that the extraperitoneal testicle is separated from Figure 8. Showing method of operating on adherent hernia of sigmoid : peritoneal flap prepared for closure of ring : purse-string and continuous suture for formation of new mesentery almost completed. tlie ^'Ut, not only by the parietal peritoneum, liut also bv the double fused layer of agglutinated mesocolon. In our many cases of retained testes, we have never encountered any such adhesion. It is just as impossible to pic- ture an adhesion occurring between the kidney and intestine as between the testicle and intestine. However, even granting the possibility that this adhe- sion might occur, the disproportion in size between the testicle and colon would result not in a descent of the colon, but rather in a retained testicle. Another theory almost too futile to deserve serious consideration has been advanced by Savariaud. He supposes that the bowel slips out from its mesentery as a glove finger is everted, passes behind the peritoneum and so on into the ring. Considering that the true length of the colic mesentery, though adherent, extends from the vertebral cuJuinii to the gut. this theory becomes immediately disqualified (Fig. ?i). /. LOUIS RANSOM OFF. It is evident that none of these hypotheses can adequately or satisfac- torily explain the condition under consideration. In order to truly under- stand the pathogenesis of attached hernias of the large intestine, it is essen- tial to consider the embryology of the intestinal tract, its mesenteries, and particularly the secondary changes in the mesentery of the large intestine. During the fourth week of embryonic life, the alimentary tract stretches as a straight tube from primitive mouth to anus. All but the upper portion is attached behind to the chorda by a straight double mesentery, the layers of which enclose at the base the primitive aorta. The first differentiation of this tube into its separate parts begins with the development of a small spindle-shaped enlargement, the stomach. The rest of the alimentar)- tube is still connected with the yolk sac. The further alteration in the shape and position of the alimentary tube and its mesenteries is due to the dispropor- tionate lengthening of the tube, that is, disproportionate to the development of the abdominal cavity. Consequently, to find room, the intestinal canal must take a winding and tortuous course. The stomach is the first portion of the intestinal tract to begin its axial rotation, turning so that the left side becomes the anterior surface and lesser curvature, the right side the posterior surface and greater curvature. This brings the pylorus slightly to the right of the median line, and begins the twisting of the intestine. The twisting of the small intestine takes place about the origin of the superior mesenteric artery, and both it and the large intestine rotate in the direction opposite to that of the hands of a clock. In an embryo of six weeks the intestinal tract, greatly increased in length, has already formed two distinct loops both running in an anteroposterior direction. In these loops can be recognized the rudiments of the two mes- enteric systems, the great or superior and the lesser or inferior (Fig. 4). From the pylorus the intestinal tube runs directly backward to the verte- bral column ; from here a sharp bend downward and forward toward the umbilicus ; from the umbilicus back to the vertebral column and then straight on to the rectum. The U])per loop consists of two nearly parallel arms connected to the vertebral column by a sagittal mesenterv. in which runs the first evidence of the superior mesenteric artery. At the apex of the loop is the now occluded viteline duct. A little further toward the caudal end of the embryo is found a slight enlargement, the beginning of the large intestine. At this stage the lesser or inferior mesenteric system can also be distinguished near the caudal end of the embryo. During the third month further changes occur in the size and position of the stomach. As these changes, however, are not germane to the subject under consideration, it suffices to say that the twisting of the stomach and its mesentery results in the formation of the bursa omentalis. The changes in the small and large intestine, particularly the variations in the relation of their mesenteries, are of paramount importance to the comprcliensive ex]:)osition of hernias of the large intestine. The duodenum is the only [xjrtion of the small intestine which RAXSOHOFF MEMORIAL VOLUME retains its early embryonic position. It is attached to the vertebral cokimn bv a short mesentery, which early fuses with the parietal peritoneiun, thus ])ernianently fixing the duodenum in place. The increase in length of small intestine is accomniodated by the folding of its mesentery in a frill shape, the base narrow and the outer edge of great length. The most important change, however, takes place in the position of the large intestine and its mesentery. This fact must always be borne in mind : the large intestine at all times possesses a long mesentery and is at no ^tage or in no part extraperitoneal (Fig. 3). The caecum is at this stage rotated across the abdomen from below upward and from right to left and again to the right, until it occupies a position under the liver. This ascend- ing loop, which later forms the entire large intestine, thus crosses the loop of small intestine from below upward and from right to left, crossing at the duodenum, carrying its mesentery with it. This explains why the duodenum is buried under the transverse mesocolon (Fig. 5). The cjecum, in the adult sense of the word, is not yet developed, as it is not an integral part of the embryonic large intestine, but a pouching or evagination of its wall. The transverse colon as in adult life crosses the duodenum to jhe splenic flexure and from there on the descending colon to the rectum. In later embryonic life the ca?cum descends toward the right pelvis, forming the ascending colon. This description has been undertaken to show that the entire large intes- tine has a distinct mesentery and lies free in the abdominal cavity. The large intestine forms a horseshoe, outlining the confines of the peritoneal cavity. Grouped in the center are the small intestines (Fig. 5). The secondary adhesions, which now form, change the mobile fetal large intestine into the fixed adult type. Peritoneal surfaces have a tendency to adhere when they are held in con- tact under pressure. The small intestine, and particularly its mesentery, does not adhere to the parietal peritoneum, for two reasons : (1) From the time of the development of the liver in the fifth week, the small intestines are filled with its secretion, and in a state of active peristalsis; (2) its frilled mesentery presents no broad surface for agglutination. The conditions in the large intestine and its mesentery are the reverse. (1) The broad flat mesentery stretching on either side from the verte- bral column to the large gut rests directly on the posterior parietal peri- toneum (Fig. 4). Moreover as the large bowel is empty and not in active peristalsis, it is immobile. (2) The mesentery is held in contact to the posterior parietal peri- toneum not only by the pressure of the filled moving small intestines, but also by intra-abdominal pressure. (3) Still another feature is the increase in local pressure at the site of the projecting kidneys and adrenals, which force the parietal peritoneum in direct contact with the ascending and descending colon. Page ise J. LOUIS RANSOHOFF. The adhesion of mesentery always ])recedes the adhesion of the bowel ; that is, the adhesions begin at the root of the mesenteries and spread toward bowel. Failure of the adhesions to be continuous results in tlie ileocrecal fossa on the right side, the parasigmoid on the left (Fig. 3). The agglutination of the large intestine begins at the transverse meso- colon, which adheres to the great bursa. The transverse colon, however, retains its mobility by the mobolity of the bursa itself. According to Brow- man, the limits of adherence of the ascending and descending colons depend entirely on the retroperitoneal position of the kidney and adrenals. Only those portions of the colon lying directly on the anterior surface of the kid- ney and adrenals adhere, which accounts for the comparative mobility of the caecum and ileopelvic colon, both of which lie below the level of the kidney. This explanation of the mobility of the cascum and pelvic colon, while very plausible, does not explain those cases in which the entire descend- ing and ileopelvic colon is found adherent to the posterior peritoneal wall (Fig. 6). The theory, which seems more plausible, is that advanced by Lardennois. that the secondary adhesions of the large intestine begin at two points: on the right side at the hepatic flexure, at the entrance into the mesentery of the highest branch of the right colic branch of the superior mesenteric artery (Fig. 6) ; on the left side at the splenic flexure, where the highest branch of the inferior mesenteric artery first enters the descending mesocolon, this adhesion being continuous with the phrenocolic ligament. It is interesting to state here that no matter how great the ptosis or disloca- cation of the colon, the hepatic and splenic flexures are invariably found in their fixed positions. Beginning at the hepatic flexures on the right side the mesentery of the ascending colon adheres along its entire length, the adhe- sions increasing in extent as the head of the colon descends. The adhesions begin at the inner border of the mesentery and spread toward the peri- ])hery. The cjecum being a pouching of the head of the large bowel has no mesentery and, therefore, does not adhere. The extent of mobility of the caecum depends entirely on its length ; a short caecum being only slightly mobile will never be found in a hernial sac, while a long, freely movable cascum has almost the same opportunity of entering the hernial sac as a coil of small intestine. This comparative mobility of the caecum is often observed during operation in the appendix region. Every operator realizes how sim- ple it is in some cases to deliver the cascum through a gridiron incision and how difticult in others. The adhesion of the descending colon begins at the splenic flexure and passes progressively downward along the whole course of the posterior abdominal wall to the brim of the pelvis. It is necessary at this point to consider the measurements of the dift'erent parts of the colon. The left colon is arbitrarily divided into the descending and ileopelvic portions. The length of the descending colon is fairly con- stant, measuring about 14 cm. The ileopelvic portion on the other hand varies within the enormous limits of 14-81 cm. Evidently the longer the Page I,H1 RAXSOHOFF MEMORIAL VOLUME colon the greater will be its mobility, as only that portion will adhere which comes into direct contact with the ])Osterior jieritoneuni. An extremely long ileopelvic colon partakes of the nature of the small intestine, and for this reason has the same chance of entering the hernial sac. A short colon stretched from the splenic flexure to the rectum would be adherent along its entire length (Fig. 6), and this brings out the crucial point, it could not [jossibly become engaged in a hernia. What is the cause of the adherence of the large intestine, when it finally gains access to the hernial sac? Its early reducibility is sufficient proof, that in the beginning it is nonadherent. The reason for its adherence is that under resumed embryonal conditions it follows its embryonal tendencies. In the hernial sac, the broad flat mesentery of the large intestine comes into direct contact with the peritoneal surface of the sac. Moreover, the two peri- toneal surfaces are held in contact under considerable pressure, as the large intestine, particularly by pelvic colon, is usually distended with faeces. Be- side, the large intestine, unlike the small intestine, is comparatively immobile and seldom in a state of active peristalsis. Thus we have the requisites for peritoneal agglutination present: (1) Broad flat surfaces held in contact under pressure; (2) comparative immobility. As in embryonic life, the adhesions begin behind, at the attachment of the mesentery, and progress steadily around the sac (Figs. 1, 2, and 7). There are cases reported of so-called hernias without sacs, where the entire sac has been obliterated by these adhesions. To recapitulate: After studying the embryology of the large intestine and the secondary adhesions of its mesenteries, the following conclusions may safely be drawn : 1. So-called hernias with incomjilelc sacs do not exist, except as a sec- ondary process. 2. The sac is complete in its incipiency and has been obliterated by secondary adhesions of the embryonal type. 3. A loop of intestine found in a hernial sac is conclusive i)roof that originally that loop was mobile. 4. hi adherent hernias of the large intestine the hernia is i)rimary. the adhesions secondary. 5. The crux of the situation is the redundant colonic loop. Morphologically, three forms of hernia of the large intestine may be dis- tinguished, the varieties based on the relationship of contents to sac: 1. The sac is complete. That is. there are no adhesions between the sac wall and gut. This form differs in no wise from the ordinary reducible hernias of the small intestine. The loop of the bowel and its mesentery are easily reduced. This form of hernia occurs when from an early stage in its existence the hernia has been kept in jilace by a truss, and no chance has been given for the formation of adhesions. 2. The most common form of hernia of the large intestine is that with l)artial obliteration of the sac by secondary adhesions, tlie SD-called hernia /. LOUIS RANSOM OFF. with incomplete sac (Figs. 1. 2, and 7). The posterior portion of the sac has become obhterated by adhesions beginning at the mesentery behind and extending to a variable distance around the sac. The entire loop of bowel is usually found adherent, beginning below at the base of the sac and extend- ing to the neck. When the cjECum and appendix are engaged in a hernia, the adhesion begins at the broad flat mesentery of the head of the colon and the first loop of the ileum. 3. Hernia with complete obliteration of the sac, the so-called sacless hernia, is extremely rare and very few cases have been reported, '{'here is .some doubt whether this form of hernia really exists, and whether some portion of the sac, however small, is not always preserved. These adherent hernias of the large intestine are seldom strangulated, probably due to the large size of the ring, which has been enlarged by the thick-walled large bowel and its semi-solid contents. On the other hand, inflammation and the presence of fibrinous exudates in the sac are not of unusual occurrence, as in Case I. This is perhaps due to an injury of the irreducible gut, and the migration through its wall of bacteria. On opening the sac by a hernia-laparotomy incision, it is found that the adhesions of the gut to the posterior surface of the sac are continuous with the mesosigmoid, or with the normal reflexion of the peritoneum to the posterior abdominal wall. The gut is continuous with the pelvic colon or with the ascending colon as the case may be. The adhesions are so dense that it seems as though the sac is really deficient behind. What is most important is the fact that the nutrient vessels of the bowel are found in the adhesions. An attempt to separate these adhesions by blunt dissection is unsuccessful. The anterior part of the sac is free, the posterior wall is formed by the loop of gut, which seems to be really incorporated in the wall of the sac, the peritoneum of the sac appearing to be continuous with the covering of the bowel (Fig. 7). There are frequently other contents of these hernial sacs. On the right side the first coil of ileum with its mesen- tery may be found adherent in the sac, on the right or left side free coils of small intestine. Unless strangulated, the small bowel is easily reduced, leav- ing the hernial sac with the large bowel attached to its wall. In some in- stances the adhesions may be so dense as to include the extraperitoneal testi- cle and cord. Cases have been reported in which the testicle was so adher- ent that it was necessary to sacrifice it before radically curing the hernia. This, however, seems in the majority of cases unjustifiable. Symptomatology. — Though the symptoms of these hernias are not in any way distinctive, there are certain suggestive features which point to the pos- sibility of a diagnosis being made. Usually occurring in males, these hernias come on after adult life. At first reducible, they become irreducible after months or sometimes years. If sigmoid hernias, they have a doughy feeling and cause their bearer less discomfort after a thorough evacuation of the bowels. If a hernia of this sort is suspected, the diagnosis could easily be made by the injection of bismuth per rectum, followed by a radiogram. It RANSOHOPF MEMORIAL VOLUME is during operation that the diagnosis can and must be made, as only by pre- cisely understanding the condition present can proper treatment be insti- tuted. After exposure and isolation of the sac in a radical herniotomy, it is the practice of many surgeons to attempt to reduce the contents before opening the sac. If this maneuvre is unsuccessful, an immediate suspicion of adherent hernia should be roused, and the greatest precautions taken to obviate injury to the bowel. The sac should be palpated with the gloved finger and a non-adherent portion found, which is invariably in the anterior portion of the sac. Grasping this non-adherent portion of the sac with forceps, it is lifted free from the underlying contents and opened by a .small incision. The opening is enlarged upward toward the neck of the sac pre- ceding the incision, with the finger or grooved director. In extending the opening of the sac downward, it is well to exert great care not to injure the cross loop of the bowel. After freely opening the sac, if this form of hernia is borne in mind, the diagnosis can surely be made. If a gentle attempt is made to separate these adhesions, it will be found unsuccessful without using undue force. In fact any attempt to separate these adhesions is unjustifiable and may result in disaster. Treatment. — According to Weir, Heydenreich attempted this manoeuvre in two cases, both followed by fecal fistula and recurrence of the hernia. Numerous like disasters have been reported. Fearing a similar result, Jaboulay resected the entire adherent loop of bowel. No matter what method of treatment is followed, it is essential that the neck of the sac should be well exposed. To accomplish this exposure, it is frequently necessary to perform a hernia-laparotomy. This is done by intro- ducing the finger through the internal ring and cutting the internal oblique to a variable extent above the ring. After this is done, one of several meth- ods of treatment may be instituted. Savariaud's method is in fact a reduc- tion of the sac and bowel en masse. This method was practiced in Cases I and II. In order to thoroughly complete this operation, the sac and its con- tents must be well exposed above the internal ring, which must be stretched sufficiently wide to permit the passage of the sac and its contents without using undue force. In his original description of the operation, Savariaud advised the closure of the incision in the sac wall before reduction is at- tempted. The sac and its contents are then forced through the internal ring as though inverting a gloved finger. The ring is closed by bringing the edges of the inverted sac in apposition by interrupted sutures. The operation is completed as an ordinary herniotomy. The disadvantages of this operation are the insecurity of the closure of the ring and the danger which always attends the reduction of a hernia en masse. That is, there is a possibility of later strangulation within the reduced .sac. The operative procedure followed in Case III, which is a slight modi- fication of a method described by Hotchkiss in 1910, seems to offer greater advantages in that it results in a return to fairly normal anatomical relations. After division and thorough exposure of the sac (Fig. 7) it will, as a rule. Page i90 /. LOUIS RANSOHOFP. be seen that one side of the sac is of greater width than the other. In this event the more ample peritoneal surface is chosen as a flap to cover tiie ring. In case the peritoneal surfaces are of almost equal extent the mesial portion of the sac should be utilized for this purpose. The portion of the sac chosen as a covering for the ring is separated by an incision beginning at the bottom of the sac and running parallel to and at least one inch from the gut wall. The flap is completely freed below, left attached above to the peritoneum covering the internal aspect of the ring (Fig. 8). The loop of bowel is now pulled out well through the ring and reflected on the abdomen. The attached flaps of the sac are now united on the posterior surface of the bowel by a fine running catgut suture, thus form- ing a new mesocolon. The suture is begun above at the cross loop of the bowel by using a wide purse-string suture so as to prevent angulation. After the continuous suture is completed, the loop of bowel is easily reduced. The ring is closed by suturing the prepared flap of peritoneum to the peri- toneum covering the internal ring. The margins of the internal oblique, if divided, are exactly approximated, and the operation completed after the Bassini method. Lardonnois and Okinji suggested that as these hernias are due to the mobility of the large intestine, they should be treated by fixing the intestine to the posterior peritoneal wall. After exposing the sac, the neck is well exposed by a hernia-laparotomy and the gut carefully dis- sected from the sac. The loop of large intestine is then sutured as high as possible to the posterior peritoneal wall as in colopexy. In extreme cases it might be well to combine this procedure with the method of operation described above. In a class of cases presenting so many difficulties, prob- ably no one method of treatment will be applicable to all cases, and a combi- nation of two methods may occasionally be of advantage. The following cases are from the records of Dr. Joseph RansohofT and the writer : Case I. U. L., aged 54. Complained of left inguinal hernia, which had been present for many years, but had only become irreducible during ])ast two years. Examination revealed a left irreducible inguinal hernia, the size of an orange. Operation (Jewish Hospital, March 7, 1908). Cas-ether anesthesia. After opening the sac the descending colon was found adherent to its pos- terior wall. The gut and sac were reduced en masse, and the ring closed by suture. The operation was completed as a typical Bassini. The recov- ery was uncomplicated and there has been no recurrence. Case If. A. L., aged 53. Had had a hernia for two years, which became irreducible during the last two months. During past two days the hernia was swollen, tender and painful. Examination revealed a, tense irreducible left inguinal hernia, the size of two fists. Operation (Jewish Hospital, May 13, 1909). Gas-ether anesthesia. After exposing the sac in the usual way, incision into it revealed the in- flamed and thickened sigmoid loop adherent to the posterior wall of the fac. RANSOM OFF MEMORIAL VOLUME Gut and sac were reduced en masse and the ring closed by the suture of the inverted sac wall. The operation was completed as a typical Bassini. Recovery was uneventful, and there has been no recurrence. Case III. D. B., aged 59. Had an irreducible inguinal hernia, which had been present for twenty years. During past three years hernia had become irreducible. Examination revealed a \ery corpulent man with a large, irreducible, left inguinal hernia. Operation (Jewish Hospital, July 29, 1911). Gas-o.xygen-ether anes- thesia. After exposing the sac in the usual way, an attempt to reduce its contents before opening was unsuccessful. On opening the anterior part of the sac, a loop of the sigmoid about ten inches long was found adherent to its posterior wall. The neck of the sac was exposed by incising the internal oblique. A peritoneal flap for the closure of the ring was made as described above. The two attached portions of the sac were united over the posterior surface of the gut by a running catgut suture. The gut with its new formed mesentery was easily reduced and the ring closed by suturing the prepared flap to the margins of the ring by interrupted catgut sutures. After care- fully approximating the cut margins of the internal oblique, the operation was completed as a typical Bassini. Recovery was uneventful, and there has been no recurrence. THE DANGERS AND FALLACIES OF INTRASPINOUS INJECTION OF SALYARSAN.* William Ravink. M. D. Cincinnati. In our zeal to combat syphilis of the central nervous system, we are prompted more by enthusiasm and theory than by reason and judgment. Time-honored weapons, which have served us well in our therapeutic amia- mentarium. are cast aside, to join the ever-growing number of faddists. The Direct Intradural Injection of Salvarsan. — Wechselman, in 1912, and Alarinesco. in 1913, reported unsuccessful attempts at the direct intra- dural injections of salvarsan. Ravaut, however, reports some favorable results from this method. A\'ile expresses confidence in the method of Ra- vaut, but ]ioints out the dangers of its use ; where there are any involvement of bladder and rectum, these constitute for him a decided contra-indication. Gordon reports a most disastrous case following the intradural injection of neosalvarsan, after the method and technique of Ravaut, a synopsis of the case which I will quote : "The patient, a man of thirty-five years of age, presented all the typical symptoms of tabes dorsalis. At the time he came under my observation, pain in the lower extrenieties, ataxia, incontinence of urine and constipation were the most conspicuous manifestations. For- merly. I was told, he had the usual course of treatment with iodids and mercury. At this time the Wasserniann reaction of serum and spinal fluid was positive. I proposed at once the treatment with auto-salvarsanizcd serum, which was promptly accepted. The result from one injection was gratifying. The pain had almost disappeared, the ataxia improved, also the incontinence of urine decreased considerably. Constipation remained unaltered. "For a period of two months the patient felt very comfortable. Soon, however, the bladder disturbance returned. As the Wasserniann reaction was at this time positive, the patient finally accepted the ofifer to have an- other intraspinal injection, which he had repeatedly refused during the past two months. With the patient's consent, I had recourse this time to the direct intradural injection of neosalvarsan instead of the salvarsanized serum. Accordingly I had the fluid prepared after Ravaut's technique. The solution used was a 6 per cent, neosalvarsan in distilled water. As each drop of the solution contained three mg. of neosalvarsan, only two drops were injected from a specially constructed and very accurately graduated syringe. The lumbar puncture was made with a needle, the end of which fitted the graduated syringe. After a small quantity of spinal fluid had flowed out of the cannula and been collected in a tube for diagnostic purposes, the syringe was attached and the fluid was allowed to run in. in order to mix * Read before the Academy of Medicine, of Cincinnati. January IS, 19Lv— From The Lancet- RANSOHOFF MEMORIAL VOLUME with the drug. Then the mixed fluid was pushed gently into the canal. The ]irocedure of mixing was repeated the second time. The patient was then placed in the Trendelenburg position. One half-hour after the injection the patient commenced to complain of severe pains in the lower limbs, which in subsequent days became more and more pronounced. Vomiting appeared on Ibe same day and kept uj) for six consecutive days. Retention of urine took the place of the former incontinence. Incontinence of feces made its appearance. All these symptoms continued without relief. On the fifth day. small erythematous patches appeared on the glans penis, scrotum and the sacrum. They gradually became larger and finally distinctly gangrenous. Two weeks after the injection the patient presented the following picture: He was unable to stand or walk; he suffered agonizing pains in the lower limbs, so that sleep was impossible ; retention of urine and incontinence of feces were exceedingly disturbing; the gangrene of the above-mentioned areas was becoming more and more profound ; the temperature reached 102 to 103° F. ; he vomited daily, lost his appetite and was losing weight, r.radually the condition grew more and more alarming and finally he ex- pired. This case seems to militate against the direct intradural injection of neosalvarsan, notwithstanding the favorable reports of Ravaut and Wile. .\nimal cx])erimentation with the direct intradural injection of salvarsan in monkeys had to be abandoned on account of the caustic and destructive action of the drug. "Tile direct intradural injection has now been for the greater part supp'anlcd by the ingenious method of the salvarsanized serum injection of Swift-Ellis, for the technique of which the reader is referred to the original article. One thing which all the writers who laud this method over all others forget to mention is this: The main reliance of tlie Swift-Ellis method lies in the intravenous injection of salvarsan preceding the intra- spinous injection, a point which the originators of the method personally mentioned and emphasized to the writer, and quoting verbatim from their original article the following: 'In dealing with syphilis of the central nervous system, we are, however, more fortunate than is the case in purulent men- ingitis, for here the introduction of our therapeutic agents into the general circulation is of undoubted benefit. With mercury, iodids and with salvarsan intravenously, much can be done, and in many patients all clinical signs and symptoms can be relieved.' " What is accomplished by the Swift-Ellis method of treatment? Wasser- mann plus is changed to negative. The number of lymphocytes in the cere- bro-spinal fluid is reduced. Globulin reaction becomes negative. In other words, the improvement shown is a biochemical or laboratory improve- ment. The high cell count and the globulin reactions are the manifestations of an inflammatory process, and it is questionable whether its reduction is going to be a distinct advantage to the patient ; we must not lose sight of bis general condition. Clinically, no results are reported aside from the WILLIAM RAVINE fact that the patients are reported as feeling better. Wiiat a variable quan- tity this is. This method is not without its dangers, as we are but to refer to the fatalities which occurred at Los Angeles in seven cases after the intraspinous injection of salvarsanized serum. The method is more painful, requiring very often opiates for the relief of pain in the legs. Paralyses of the legs. incontinence of urine and feces persisting for months, and later followed by death. Sachs reports a case of paresis developing an acute ascending paralysis of Landry after the sixth intraspinous injection, all of the injections having been tolerated with great comfort. Myerson reports several cases which grew rapidly worse after this method. One case in particular merits its rei)roduction here. Case No. 11737. — F. M. L., male, aged thirty-nine years, married; en- tered May 6, 1913. The occasion of the patient's commitment was the sud- den maniacal outbreak in the house of a friend. Family history, negative. Had a high school education. He had been a spendthrift, a heavy drinker, and led a dissolute life. At first he denied syphilis, but later admitted having it years ago. At the time of entrance he was clearly oriented. Memory seemed intact ; no hallucinations or delusions were elicited. He was some- what euphoric. Continually attempted to leave the hospital ; rather verbose in answers, otherwise showed no distinct mental symptoms ; physical signs were carefully noted at that time. The left pupil was slightly larger than the right; both reacted moderately to light, consensual and distance. Cranial nerves of the face were good. No paralysis anywhere. Slight tremor of the hands; reflexes of the arm were equal and moderate; knee jerks equal and active; ankle jerks equal and active. No Babinski, Gordon or Oppenheim. Adductors moderate; cremasters and abdominals O. K. In other words. physical examination was almost entirely negative. Blood serum positive to the Wassermann reaction to syphilis. Spinal fluid showed moderate pres- sure, albumin much increased Wassermann negative, globulin by Nonne'^ method slightly positive, likewise by Noguchi's method; cells mostly red. of which there were perhaps one thousand in the field. No blood had been drawn upon puncture, and these cells, it is evident, had not come from the puncture, since the slightly yellowish tinge of the spinal fluid could not be centrifuged out. This peculiar spinal fluid had its explanation a very shorl time afterward in the following: May 11, during the morning, the patient was restless, confused and at- tempted to get out. At 12:30 he suddenly lost consciousness, became rigid and showed some clonic movements. Recovered in about thirty minute'^. During this time there was a double Baliinski. more on the right side, rigid ])upils, absence uf abdominal and cremasteric reflexes. At 6:00 p.m. he was up and around, very euphoric and markedly confabulating. He told how he had been out all day in an automobile, and spoke of the very elabo- RANSOHOFF MEMORIAL VOLUME rate meals he had had. Showed marked loss of memory for recent events. Was disoriented for time and place. Gave irrational answers to questions on educational matters. Lumbar puncture done at this time shows that spinal fluid was under high pressure, was yellowish in color, and contained very many red cells, although no blood had been drawn by the puncture, and. as before, the color could not be centrifuged out. The Wassermann reaction in the blood was still positive. At this time there was positive U'assermann reaction of spinal fluid. The globulin was distinctly positive. From this time, for a period of a month, the patient had marked euphoric delusions. He was to marry a nurse of the ward ; he had $50,000, a motor boat, and a Fierce-Arrow automobile was to take him and his bride all over this country and to Europe. He denied that he was married, and said most emphatically that the nurse, who was possessed of all the virtues of her sex, both in person and character, had promised her hand to him as soon as he could get out. He had schemes for making money. Gradually this euphoric state disappeared. TKi:.\T.MKXT Mav 14. .45 gr. neosalvarsan. May 21. .45 gr. neosaharsan. May 24, 20 c.c. scrum intradurallv ; Wassermann reaction serum posi- tive. Ma\ 2^. .9 gr. neosaharsan ; Wassermann reaction serum negative. May 31. 30 c.c. serum intradurally: \\'assermann reaction serum nega- tive. June 6, .6 gr. neosalvarsan. June 7, Wassermann reaction, serum slightly positi\e ; 20 c.c. serum injected intradurally. Spinal fluid at this time >liowed still the slight yel- lowish tinge, although no red cells were to be seen. This yellowish tinge persisted for some time, and was probably due to hemoglobin and to dis- solved coloring matter from the red cells. Finally it disappeared and the fluid became clear. June 11. .45 gr. neosaharsan; Wassermann reaction spinal fluid nega- li\e. June 14. Wassermann reaction serum positive. June 19. .9 gr. neosalvarsan. June 21. 30 c.c. serum intradurally; Wassermann reaction serum ncga- ti\ e ; spinal fluid suggestion of positive. July 2, .9 gr. neosalvarsan. July 7, 30 c.c. serum intradurally. Spinal fluid at thi> time, live cells: globulin slightly jjositive ; albumin distinctly increased; suggestive positive Wassermann serum slightly jjositive. July 16, .9 gr. neosalvarsan. Paijc VJ6 WILLIAM RAVINE Tilly 19, 30 c.c. serum iiitradurally, ten cells; globulin strongly positive; albumin increased; Wassermann reaction in serum and spinal fluid negative. July 30, .9 gr. neosalvarsan. August 2, Wassermann reaction serum positive. August 9, another physical and mental examination was made. He does not remember the two weeks following the convulsions. Following that, however, his memory is clear. He laughs at his former delusions concern- ing the nurse, likewise his wealth. He spontaneously states that he has been losing his memory for some time before he came to this hospital, likewise losing his ambition, and that he was cranky at home. No pains ; occasional dizzy spells. Physical examination at this time shows very important changes. The right pupil showed almost no reaction to light ; the left showed prompt consensual and light reaction. The right arm reflex is lively ; greater than the left : knee jerks are equal ; right ankle jerk is active ; left ankle jerk very slight. No L5abinski, Gordon or Oppenheim. Mental ex- amination by the Binet-Simon and Healy tests showed no distinct defects. By careful psychological tests for memory defect, and by the ordinary psychiatric examination, nothing of a pathological nature was found. He took an active part in the social life of the ward, and was one of the lead- ing spirits among the patients. August 13, .9 gr. neosalvarsan. .\ugust 16, 30 c.c. serum intradurally ; Wassermann reaction serum slightly positive ; Wassermann reaction spinal fluid negative. September 13, serum positive ; treatment discontinued. October 29, note was made that his condition was unchanged. December 24, discharged to the Taunton State Hospital. Diagnosis, general jiaresis; condition unimproved. At the time of his discharge from the Psychopathic Hospital, the pa- tient had commenced to become grandiose again. He exhibited eccentrici- ties of conduct, and is said to have had a hysterical outburst. This out- burst the patient describes differently. He said he had a numb feeling in his head and in his right hand, that while he knew the words he was to say and use he could not utter them. Neither could he write, although he could read what was brought to him. \\hen he attempted to make himself under- stood by the physicians he spoke nonsense and realized that it was non- sense. By his description there was a cerebral condition of some kind, transitory in nature, marked by motor ai)hasia and confusion, with numb- ness of the right hand. Physical Examination at Taunton. December 26. — At this time the pupils are Argyll-Robertson on both sides; tremor of tongue; blunting of sensation of right side of face ; arm reflexes as before ; left Achilles di- minished. No Babinski, Gordon or Oppenheim. Cremasterics present. Left upper and lower abdoininal absent ; ophthalmoscopic negative. JVIental examination at this lime shows verbosity, pomposity, euphoria and delusions of grandeur, mostly of a sexual character. He is to marry RANSOM OFF MEMORIAL VOLUME a nurse at the Phychopathic Hospital, and they are to go on a long trip together. He is to furnish the home. She is the most beautiful and vir- tuous of women. Orientation is intact ; memory is good ; no hallucinations ; acts ^uperior to his environment ; somewhat irritable and troublesome among the ]iatients ; ^^'assermanu reaction in spinal tluid positive ; albumin mod- erately increased; thirty lymphocytes; serum positive. Snmiiiary. — This patient, at first considered a case of cerebral spinal syphilis, is now considered a general paretic. First, the history of cerebral accident ; second, the euphoria, grandiose ideas, etc. ; third, the gradual de- velopment of Argyll-Robertson pupils and the gradual change in reflexes ; fourth, the appearance of all the four reactions in blood and spinal fluid plus the albumin increase in the latter. He has shown fluctuations in the W'assermann in blood, and there was present in the spinal fluid evidence of a hemorrhage which has made its way into it. Undoubtedly the first flare up was a hemorrhage into some part of the brain, and it is very prob- able that the second development of grandiose ideas started with some cerebral attack. It is to be especially noted that the Argjll-Robertson pupils developed in this case despite the use of salvarsan and the use of salvar- sanized serum, and for that reason I think this case of crucial importance in determining the value of the Swift-Ellis method. It is claimed that the value of the Swift-Ellis over any other method lies in the fact of the inaccessibility of the nervous system through the blood stream. The effects of bromide, chloral, opium, alcohol, strvchnia. and certain of the toxins of the infectious diseases, seem notably to affect the brain and nervous system through the blood stream. Professor Benedict, of the Cornell Medical School, made an examina- tion of four specimens of spinal fluid twenty-four hours after intravenous injection of salvarsan (0.4) and found that the spinal fluid contained free arsenic in about one-sixth to one-tenth the concentration in the whole blood. This is a striking fact and is contrary to the usual belief that none of the drug administered intravenously finds its way into the spinal fluid. This same investigator found more free arsenic in the spinal fluid after an in- travenous injection of salvarsan than is found in the salvar>anized serum as used for intraspinal injection. The injection of a serum into the cerebro-spinal siKice can. and does, affect a condition which is purely meningeal in its involvement. In tabes and paresis, in addition, we have a destructive process present, which condition we should not make worse by the intradural injection; also the general health of the patient must be conserved. "Forsake not an old friend, for the new is not cuniparal)le lo him. A new friend is as new wine ; when it is old thou shalt drink it with pleasure." Mercury and the iodids have been tried in countless cases and they have n(jt been found wanting. They have in the past, and will in the future, benefit our cases of .syphilis. WILLIAM RAllNE The writer has been able to bring about the same cytological and chem- ical changes that have been accredited to the method of Swift-Ellis, with mercury and the iodids alone, and in some cases combined with salvarsan intravenously. A case that I treated at the Kracpclin Clinic at Munich will illustrate the changes that can be brought about in the siiinal tluid by the use of mercurial rubs, four gni. daily, plus one intra\enous injection of .9 neo- salvarsan. Mr. J. \\".. aged thirty-three, was brought into the clinic by the ijolice, December 11. 1913, wlm had found him wandering aindessly about in the outskirts of Munich. Physical and mental examination at the time of entrance revealed the following: He was disoriented as to time and place, there was a marked dysarthria; no delusions of grandeur. Left to himself, he wanders aimlessly about the examining room, bumping into chairs and tables; he understands spoken language, attempts to read, but confabulates; handwriting is unintelligible. Physical examination: Pupils are unequal, react sluggishly to light and accommodation, ophthalmoscopic examination, bilateral choked disc, increased patellar arm and Achilles reflexes ; slight Romberg. Clinical diagnosis, paresis; serological diagnosis was lues cerebri. Was- .sermann reaction of blood ])ositive ; Wassermann reaction in spinal fluid negative, and on larger concentrations positive ; globulin reaction was posi- tive. Cells in spinal fluid, 1,042, the largest amount they had ever seen in a case (the serologist who counted the cells with me considered it a typical American finding). He was put to bed and given mercurial rubs, four gm. daily. December 16. lumbar puncture was done; showed 949 cells; other re- actions same. December 22, lumbar puncture was done ; showed 749 cells ; other re- actions same. December 25. luniljar puncture was done; showed 367 cells; other re- actions same. December 29, lumbar puncture was done; showed 625 cells; other re- actions same. January 6, lumbar puncture was done; showed 405 cells; other re- actions same. Choked disc at this date is almost entirely disajipeared ; talks rational and is oriented as to time and place. January 13, lumbar puncture was done; showed 200 cells; all the other reactions positive. January 14. be was transferred to the "Quiet Division." January 20, be was given .9 neosalvarsan intravenously. January 27. lumbar i>uncture shciwed lifty-live cells, with all the other reactions positive. RAXSOHOfF MEMORIAL VOLUME January 28. his relatives took him out of the hospital against the advice of the hospital stafif, but he was entirely clear mentally. Summary. — (1) Daily rubs of mercury, four gm. ; the cell count was reduced from 1.042 to 200, and after one intravenous injection of neosal- varsan it was brought down to fifty-five cells per c.cm. (2) Mentally he had entirely cleared u]i. (3) Choked disc almost entirely disappeared (4) The Wassermann in blood and spinal fluid remained positive. Dr. Sachs, of New York, bears out this statement in a series of cases that they have had. It is also interesting to note that in a few cases that were not treated, which showed a decrease in the cell count of the cerebro- spinal fluid as well as remissions clinically. The rationale of treatment in syphilis of the central nervous system is : (1) Conserve the general health of the patient. (2) Increase the leuco- cytosis of the patient, as we know in this way all infections are combated ; this can be done by the injection, subcutaneously, of nuclei acid. Some European investigators believe in placing the patient in an electric light cabinet; in this, produce what they call an artificial fever. (3) K. I. by mouth. (4) Mercury, rubs or deep muscular injections. (5j Salvarsan or neosalvarsan intravenously or over the fascia lata. (6) Periods of inter- mission of the anti-specific treatment for one of tonics. Summary. — (1) The direct introduction of salvarsan and neosalvarsan into the spinal canal has been almost entirely abandoned, as it is fraught with the greatest amount of danger. (2) The chief reliance in the Swift- Ellis method is in the initial intravenous injection. (3) The nervous system is accessible through the blood stream as arsenic is recovered from the spinal fluid after intravenous injection of salvarsan. (4) The amount of arsenic injected by the Swift-Ellis method is only infinitesimal, and the changes brought about are no doubt due to the initial intravenous injection, or to the repeated lumbar punctures, or to the dilution of the cerebro-spinal fluid. (5) The changes brought about by this method are only those of the labora- tory ; clinical recoveries are not reported ; fatalities have resulted and cases have been decidedly made worse. (6) This method has not supplanted the time-honored use of mercury and K. I., plus our new addition, s.ilvarsan. (7) The method is one that requires the greatest care as to asepsis, requires a full laboratory equipment, and can only be used in a well-organi,'ed hos- pital, and is not applicable for the general practitioner. It is very painful, opiates having to be given to relieve severe pains in the extremities. BIBLIOGR.\PHY The Tre:itment of Syphilitic .\ffcctions of the Central Nervous System with Especial Refer- ence to the ITse of Intraspinous Injection. Swift-Ellis, Archives of Internal Medicine, Vol. 12, No. 3, page 331. Results of the Swift-Ellis Intradural Method of Treatment in General Paresis. A. Meyerson, Roston Mel, ani-(enil.i-r. 191y.- I'rum Surgery. |-.w„.,.,jl..i,.y ,,,,,1 Oh^iet. i.-s .Npril. 19:0. /'one an M. G. SEELIG ber, compared with the number of alcoholics: and that many cases of rhino- phyma occur in non-drinkers. The commonly accepted opinion is that rhinopliyina. pathologically speak- ing, represents the terminal stage of acne rosacea that has passed llirough acne hypertro])hica. In manj' instances the disease seems to rest on a con- genital basis ; Lassar believed that there was a predisposition to rhinophyma in wide-pored individuals. The essential pathological process is an hyper- plasia of tlie connective tissue of the soft parts of the nose, accompanied by a dilatation of the blood vessels, and hypertrophy or cystic degeneration of the sebaceous glands. The skin follicles show, in places, di.stinct evidences of suppuration. The openings of follicles and of the ducts of the sebaceous glands are widened, so that they resemble deeply-pitted pores, often giving to the nose the appearance of a sponge. Xo one has e\er satisfactorily Fig. 1. Rhinophyma lieforc operatidii Fig. 2. Profile, saint- patient. demonstrated the cause of the disease. Kai^osi sought to prove that the connective-tissue growth, blood-vessel dilatation, and sebaceous-gland de- generation were all secondary to an angioneurosis ; but there is no marked consensus of opinion concerning this theory. Trendelenburg considered the disease as a new-growth and grouped it under the head of, tibroma mollus- cum ; L.assar considered it a cysto-adeno-fibroma. I am indebted to Dr. Martin Engman for the privilege of quoting from the advance sheets of his forthcoming book on Diseases of the Skin. Dr. Engman from an intensive study of rhinophyma, draws the following con- clusions regarding the pathology of the disease : "Rhinophyma is a familial disease representing some type of hereditary transmission. It occurs usually in the seborrhoeic type of individual. (The seborrhceic type of Sabouraud may be described as an individual with yellows-tinted, muddy, thick skin, the yellowish tint being most pronounced around seborrhceic areas, with a tendency to acne vulgaris in youth and acne rosacea in middle life.) 'i'he RAXSOHOFF MEMORIAL VOLUME future rhinophyma subject shows a tendency toward flushing of the face, on entering a warm room, after meals, or under excitement. This flushing leads, in time, to a chronic congestion, with secondary chronic infection of the skin of the nose and sometimes of the cheeks. This in turn leads to a chronic ]:)roductive inflammation, w-ith vascular dilation, connective-tissue- formation and dilation of the sebaceous glands into cyst formations. There is a marked thickening of the cutis vera, which throws the skin into folds and furrows. The end-result is the multiple formation of knobs or tumor-like masses." The treatment of the disease is exclusively operative. The occasional recommendation to practice wedge-shaped incisions should be ignored. The most satisfactory operative procedure consists in shaving ofT the redundant tissue until the nose is brought back to what one assumes was its original Fig. 5. Unknown subject, painted bv Holbein the vimnger (1497-1553"). Hangs in the Prado of Madrid. (From HoUactidcr.) Fig. 6. Portrait of supposed grandfather and grandchild of Ghirlandajo 0449-1494). Hangs in the Louvre. (From HoUacnder.) Fig. 7. Unknown sitter bv a Holland master, in Museum at Stockholm. ( From Hollacndcr.) form. In this shaving process, two things should be borne carefully in mind : (1) do not shave too deeply; and (2) preserve a thin rim of epithelium around the snares. If the shaving is carried too deeply, we remove all se- baceous-gland rests and leave no niduses of epithelium from which, as brood centers, epithelization may spread. This delays healing, and even if the nose be grafted, the resultant skin has a harsh, white, dry appearance so striking as always to command attention and cause comment. Further- more, deep shaving may injure the nasal cartilages and set up a stubborn perichondritis. If a thin ring of intact skin is not left around the snares, serious disfigurement may result from the contractions incident to cicatriza- tion. H;emorrhage, which i.^ u.'~ually very free, is checked with comparative Page r.ii; M. G. SEELIG ease by simple gauze pressure, and the patient is sent to bed with a large, well vaselined gauze pad over his nose. The next day this pad is removed, and the denuded area is strapped with imbricated strips of sterile zinc oxide adhesive plaster. This plaster dressing is changed daily. Under this simple dressing, my patient, shown in Figures 1 to 4, was completely healed in ten days. It is not necesary to skin graft these patients. Indeed, von Bruns [Joints out that grafting often leads to the development of retention cysts underneath the grafts, with subsequent breaking through and ulceration. The role that rhinophyma plays in medical history and in classical art and caricature is not totally without interest even to a group of practical surgeons. Dr. Eugen Hollaender in his two volumes devoted to Medicine m Classical Art and Caricature and Satire in Medicine furnishes some strikin:^ copies of pictures that feature rhinophyma. Fig. 9. Fig. II C.erhard Janssen, an old gias.'; etcher of the middle seventeen tury. (From Hollaender.) .\ caricature from the seventeenth century. One of the so-called Kings of Noses. (From Hollaender.) .\ caricature of a physician, published about 1700 in Augsburg. (See text for translation of legend.) (From Hollaender.) Hans Holbein, 1497-1553 (known as Holbein the younger), famous in medical art as the painter of the Dance of Death, painted the portrait of an unknown subject (Fig. 5). The portrait, which hangs in the Prado at Madrid, shows an old man, with a typical rhinophyma, and the characteristic red, congested color scheme which goes with this disease. Hollaender states that the coloring seems to have been toned down by the artist, in order to minimize the existence of the disease as much as possible. Donienico Ghirlandajo, 1449-1494, the famous Florentine artist, has a I)iclure in the Louvre illustrating rhinophyma even more typically (Fig. 6). A'. IXSOIIOJ^ MJ^MORIAL I'OL UMI: HoIIaeiider's speculations of this particular picture are interesting rather than convincing. He queries as to whether the small tumor on the right brow of the old gentleman may not be intended as a metastasis, thus hint- ing at the possible belief that rhinophyma was at that time considered to be malignant. Then further, he speculates as to whether the beautiful child's head was intended to soften, by contrast, the jarring asymmetry of the bul- bous nose of the old gentleman, or whether the perfect featured little grand- daughter was used to disprove the familial nature of the disease. Hollaender presents these two pictures (Figs. 5 and 6) and the picture by an unknown Holland master (in the museum at Stockholm, Fig. 7) to illustrate the fact that they are pure portraiture, artistically executed with- out a semblance of caricature. These portraits may stimulate a sense of sympathy but they make no appeal whatsoever to the risible in our make-up. By contrast. iMgure S leads away from art, into the field of caricature. This old rhinophyma subject. Gerhard Janssen by name, was a master glass etcher, born in Holland and trained in his art at Dresden, 1650-54. The print itself is not a caricature, but the descriptive phrases engraved about it^ furnish a caricaturish setting: such phrases, for example, as the legend just aljovc the head. Xasiitits scd aciitiis (large nosed but wise) and the sen- tence in the frame, Es ist ■:caiir cin iinfocrnilichc Nasc. abcr sinnrcichcd J'cr- staiul (a misshapen nose, 'tis true, but talented and wise). The next two prints arc frank caricatures. Figure 9 is from an old seventeenth century pamphlet and is a simon-pure bit of what Hollaender calls naive lack of humor of this period. This king of The Large Nosed stands surrounded by all sorts of impossible things, people, animals, a large horn, a mercury staff, a shepherd's staff, ships, etc., and points proudly to his rhinophymistic organ. Figure 10 is an even grosser caricature, and represents the tendency at this particular time (late 1600) to use the doctor as a scapegoat and har- lequin in jokes and on the stage. This large-nosed doctor, with what might be construed as a rhinophyma knob at the proximal and middle third of his proboscis jiroclaims : "For healthy people, I am a doctor, God help tlie sick. My large licadgear embraces profound and numerous thoughts. My costume connotes the art that I possess. W hat may be concealed in the urine, my long nose detects." 1 Tlic kn.iul abuu I the frame is a: S folloHM .\ niisshapiii nose ■ indeed, bnt a . man of t: prMsc and reward. The Ic-gend luukr ne.uh tin- i.ictuic :^: Ilerv Gerh.iwl I, from 16S0"to !■- I 1 eighty-eight yea.-, u .Uily 25,1725. l.y 1 ! ' M_. '•■;'■■ ■ ■■. M. G. SEELIG And finally, Figure 11 is not without interest from an ethnological poinl of view. Rhinophyma is fairly common in the American Indian. This is a portrait of \\"a-Ha-Gun-Ta, chief of the Chippewas (photographed hy Mr. William Burton, of St. Louis, wlio kindly loaned me this copy). There arc authentic records to show that the chief is about 127 years old. and as far as the memory of man runs he has had a typical rhinophyma. i^^€ ^ ^^^WrH-'- ^^^^^k ^^i terminating near the anterior jjortion of the veruniontanuni or within the sinus pocularis. The lower jiortion of the vesicle rests upon the ])osterior border of, and is with difliculty separated from, the prostate. This is particularly true if there has been chronic inflammation of these parts. The general direction of the long axis of the vesicle is upward and outward from the posterior border of the prostate for a distance varying from 6 centimeters to 22 cen- timeters. The angle of divergence varies in different individuals, and may vary greatly in the same individual, this depending upon a collapsed or dilated condition of the urinary bladder. The greater the bladder disten- sion, the farther are the upper j)o!es from the mid-line. This is an important fact to bear in mind when massaging or stripping the vesicles. In many cases where there has been a prolonged obstruction to the outflow of urine from the bladder, the long axis of the vesicles is at almost right angles to the vertical or mid-line of the body. Except in very short vesicles the upper pole extends to and in most specimens overlaps the ureter where it enters the outer surface of the bladder. The vesicles, except the lowest portion, are external to that part of the outer wall of the bladder which corresponds to the trigone, and are held in contact with this portion of the bladder. This accounts for the vesicle and urinary symptoms that so often accompany vesiculitis and peri- vesiculitis. It might be added that the aforementioned symptoms have frequently been treated empirically without regard to cause. ological .Association. North Central Section. Cliicago. Novcru- E. O. SMITH The close relation of the upper portion of the vesicle to the ureter ex- plains many cases of narrozved ureters due to impingement on the ureter of a pathological vesicle and its consequent thickening, plus the perivesicu- lar inflammatory tissue. All who do cystoscopic work have had the experi- ence of being unable to introduce the ureteral catheter more than three- fourths of an inch to one inch, yet there was urine flowing from the ureter. There can be no doubt but that this failure is often due to a nar- rowing of the lumen of the ureter and a fixation of it by these external adhesions from the vesicle. As a result of the fixation there is an angula- tion which the ureteral catheter can not readily pass. It is a well-estab- lished fact that a normal kidney may take bacteria from the blood stream Fig 1. Showing relations of vesicles tci prostate, vasa deferentije. bladder a and deposit them in the urine stream without damage to the kidney itself. It has further been demonstrated that even partial obstruction of the ureter will sufficiently lessen the normal activity and resistance of the kidney so that it becomes easy prey to bacteria in the blood stream. Following these facts a little further it requires no great strain on the imagination to see how chronic vesiculitis and perivesiculitis can be a predisposing factor in the development of infections of the kidney. Continuing from the posterior border of the prostate is a facial inciii- brane which extends beyond the vesicles. This can easily be separated from the normal vesicle, but with much difficulty where there has been perivesiculitis. Barnett called attention to the importance of getting beneath this fascia when attempting to expose the vesicles, either for drainage or removal. This line of cleavage once found, the rectum is safe from puncture. Be- neath this fascia is found a much thinner fascial layer which envelops the vesicle and ampulla of the vas deferens. Beneath this are other bands of Page HJI RAXSOinJff Ml-.MUkl.lL fOLUME fascia that hold in place the various loops and saccules of the vesicle. The normal vesicle is easily detached from all its surroundings except at the upper pole, where the blood vessels enter and at the lowest i)art which i> in contact with the prostate. In doing a vesiculectomy the vessels at the upper pole should be ligated before removal of the vesicle to prevent troublesome or possible fatal hemorrhage. The loss of blood from a vesicu- lotomy or simple drainage operation is negligible. In about one of every ten specimens examined, the prritonriiui ex- tended well down on the vesicles and occasionally to tiie posterior border of the prostate. In such cases, one would be dangerously near the peri- toneal cavity when operating on the vesicles. ?gostUc Long axis of vesicles I'orms nearly right angles with long axis of body. Upper, outer half of right vesicle contains pus. One specimen disclosed no distinct vesicles, but mere rudiments about one-half inch in length. Picker in a paper before the Fourteenth International Medical Congress held in London, 1913, grouped the vesicles according to their anatomical arrangement in five classes: (1) The simple straight tubes; (2) thick twisted tubes with or without diverticula; (3) thin straight or twisted tubes with or without diverticula; (4) straight or twisted main tube with large grape-like diverticula; (5) short main tube with large irregular ramified branches. This seems to be an unnecessary multiplication of classes as the large majority of the specimens I examined were of the continuous tubular type, not twisted but folded at sharp angles upon themselves many times. Most of the other varieties were simple modifications of this type. There J:. O. SMITH were a few pear-shaped vesicles, whose interior had the appearance of multiple saccules communicating with a common chanel. or vestibule, but not a distinct tube or tubule. The most iuiportant anatomical feature of the vesicle from a clinical or pathological viewpoint is the multiple sharp angulations of the tubule in a vast majority of the specimens. There can be no emptying of the vesicles except by some sort of a peristaltic wave which must begin at the blind extremity and travel along the tube towards its outlet into the ejacu- latory duct. I am inclined to believe that much of the benefit that patients derive from a properly executed massage of the vesicles is due to a stimu- lation of this normal peristaltic wave. \ery much on the same principle v*^ r*eritoneum extends to prostate veniiK \ e^ ight side iasa. Has been removed as the old-time massage and kneading of the abdomen to encourage intes- tinal peristalsis, before the days of Lane's kink, Jackson's membrane and Russian oil. "A properly executed massage," therefore, is a treatment that is not to severe and does not produce trauma. The appearance of the interior of a normal vesicle is that of fine tra- bcculations, suggesting irregularly arranged spider webs or tendrils. When this condition does not present and the tubules or saccules arc smooth in- side, there has been suppuration with destruction of the mucous lining. The vesicle wall is constructed of three layers of tissue, 'i'lic outer is a fibrous layer, beneath this is a middle layer of muscular tissue, which produces the peristaltic movements that eiupty the vesicle. The interior is covered with a mucous membrane which probably has some secretory func- tion, not fully and satisfactorily explained. The arrangement of the tu- bules gives a very extensive mucous surface with the zvorst natural drain- RAXSOHOFF MFMORIAL J-QLUME age. This, partially at least, accounts for the fact that about 50 per cent, of the post-mortem specimens examined were in some way pathological. The farther up the tubule, near the blind end, the more difficult is the drainage, hence we would expect to find most of the pathological condi- tions in the upper portions of the vesicles, where they are. Our findings in these specimens demonstrate that a simjile single in- cision, especially in the lower [lart of a vesicle containing pus, will not, ^^J/^/ Fig, 4. \-csicl can not, establish satisfactory surgical drainage. To drain properly, mul- tiple incisions are required, particularly high up on the vesicle. Judging from the specimens alone one would be led to the conclusion that nothing .short of a vesiculectomy could be effective, yet we know from practical experience that thorough vesiculotomy is followed by the most satisfactory results in properly selected cases. While these structures were discovered by Fallopius in the sixteenth century, and recognized as the seat of inflammation by Morgagnii in the eighteenth century (1745), it remained for Fuller and Belfield, about the beginning of the twentieth century, to bring to our attention the importance Page Sli E. 0. SMITH of these hollow organs as the hiding place for numerous bacteria — prin- cipally Neisser's diplococcus, and its associates, the staphylococcus, the streptococcus and the colon bacillus. It was they who demonstrated the relation between chronic seminal vesiculitis, chronic recurrent urethral dis- charge, and certain cases of arthritis. Invasion of the vesicles by bacteria from the posterior urethra is certainly a simple matter, there being required only a short trip through the ejaculatory duct, a distance of little more than one inch. Theoretically, at least, one would suppose from the very nearness of the vesicles to the posterior urethra, as compared to the epi- didymis, that the vesicles would be more frequently involved in secondary infection than in the epididymis. Who can say they are not? It may be that the frec|Ucnc\' of \oicular infections varies in direct proportion to the degree of diligence in examining these structures. )/f«)Ctf Fig-. 5. Ves Lewin and Daum examined 1,000 cases of gonorrhea, and found the posterior urethra involved in 65 per cent., and the seminal vesicles in 35 per cent. While there are no statistics at hand to prove the assumption, it seems reasonable that the vesicles could easily be infected from every case of chronic posterior urethritis, and in many cases of acute posterior urethritis. If any surprise is to be expressed, it is that they escape in anv case of posterior urethritis. W'hen looking about for "focal infectious," the vesicles must not be overlooked. Before having a few hundred' dollars worth of bridgework removed from a patient's mouth for arthritis, it would do no harm to in- vestigate the vesicles. The fact that the patient states that he has never had gonorrhea should not deter one from examining the vesicles. He may be mistaken or may have forgotten, besides a previous gonorrheal infection is not absolutely necesary. Vesiculitis may present in men who live under a high nervous tension, who indulge in sexual excesses both normal and abnormal, and who are intemperate in the use of tobacco and alcohol. Horseback riding, bicycle RAXSOHOFI^- MEMORIAL VOLUME and motorcycle riding arc contributing factors towarl the development of vesicle trouble. Dr. Robert T. Morri.s has given out for careful consideration and in- vestigation the suggestion that possibly there is some relation between "fo- cal infection" and malignancy, even though the malignancy be in some part of the body far removed froiu the focus of infection. While, at first thought, this may seem far-fetched, yet it is a study in biochemistry, which has luuch more to commend it than the suggestion a few years ago that goitie and nianimary lualignancy were produced by intestinal stasis. Titbi-rciilosis of the Z'csiclcs is i)ractically always secondary to tuber- culosis elsewhere in the genital tract. Contrary to much of the informa- tion formerly had. it was found that vesicles which felt nodular when ex- amined digitally per rectum are not necessarily the seat of tuberculosis. What was diagnosed as tuberculous nodules from palpation in some speci- ig. 0. iJciiso tissue about vesicles, vasa aud prostate, result of ehronic intlainniation. Left vesicle lias been dissected from its bed of adiiesions mens proxed to be thickened and sclerosed areas at the sharp angles of the tubules. In one specimen a small single nodule, about the size of a navy bean, was felt in the right seminal vesicle. \\'hen this was dissected out it was a very firm and completely capsulated cyst which contained i clear gelatinous material. The only cases of iiialii/imncy found were secondary to malignancy in the wall of the urinary bladder. There is no logical reason why the vesicles should not lie involved in jiriniary malignancy, and no doubt they are, yet none were found among the specimens forming the basis of this study. No calculi were found in the vesicles among our specimens. They cer- tainly are not \ery common. Dr. Eugene Fuller informed me in a per- E. O. SMITH sonal communication that in the more than seven hundred vesiculotomies that he has performed he found calcuH in only seven cases, and but once in both vesicles of the same patient. There is a case reported by James and Shunian where a seminal vesicle calculus gave rise to the same symptoms as those typical of renal colic, and it was not discovered until after a futile surgical search was made for a stone in the ureter. This is an exceptional case, and an error that anyone might have made. However, with such a case report before us, we should profit by their experience, and ever keei> tin's possibility in mind when study- ing "renal colic." The points in the study of the anatomy and pathology of the seminal vesicles that seem worthy of special mention are : (1) The wide variations in size and positions of the vesicles. (2) Frequency of vesiculitis, both suppurative and inflammatory ( fo- cal infections). (3) The close relaticm of the \esicles to the ureters and in some cases to the peritoneum. (4) The futility of .severe massage treatments. (5) The importance of multiple incisions ]\-irticularly in the distal portions, when surgical drainage is being done. (6) Palpable vesicle nodules arc not always tuberculous. Barnett, C. K. : Patholopy uf tlie Siiniiial \ . m. 1, , .ind Prostate, with Suggestions of the essity for Surgical Treatment. (J. Indian. i .\K .\--n. 1909. \'. 2, pp. 320-J2.) Harney. }.\\: Observation ou the Seminal Wsicles. (Tr, \m. .\ssn. Genito-Urin. Surg., liarney. I. I ), : KiLcnt Studies in the Patliologv of Seminal \'esicle.s. (Host. .M. and S. .1.. I, \-. 171, |i|., -y>-:.2.) Bellield, \V. r.: Pus Tubes in tile Male. Surgieal and Wiceine Treatment. (Jour. .\. M. .\.. Ceelen, W. : Kin Fibromyom dor Snmenhl.isc. C\'ircho«'s .\rch. £. path, .\n.lt., 1912, \'. 207, Felix. W.: Zur .\natomic des Duetus Kjaculatnrius, der .\nlpulla Ductus Deferenlis und der Special K.tMcn.r t.i 111. r,,lln yu iMn.lniu- ,,i ihr l'.,vl,.rini rrctbr.i. l\. \^ -M. T., 1913, \-. 97, pp. 0,S2-l,.S-l.) James and Shuman: Seminal \esical Calculus Simulating Nephrolithiasis. (Surg., Gyn. and Obstct., xvi, 1913.) Junkerman, C. K.: Hematuria and the Pathology of Chronic Seminal Vesiculitis and .\m- pullitis Under Which Latter Disorder We Get Bloody Semen. (.Med. Century, 1911, V. 18. pp. 113-15.) Lewin, A., and Bohm, G.: Zur Pathologic der Spermatucvstitis Gonorrhoica. (Ztsclir. f. Urol., 1909, V. 3. pp. M-M.) Nussbaum. M.: T'eber .len Bau und die Tatigkeit der Driisen. \'I. Der )!au und die Cyclischen XrrandenniLcn der Samenblasen von Ranafusca. (.^rch. f. mikr. .Anat.. 1912. V. 80, 2 .\bt., pp 1-^'M Ob, rnd.nf, ,. S: lleilv.it-. zur Anatoinie und Pathologic der Samenblasen. (Beitr. t. path. -Knat. w. / .AW. I'.itli . I'.'uJ. W 31. pp. 325-40.) P.t. i.Ti. (I \ I i; : Ibitr.-iKC zur .Mikrokopischen .\ualoniie der W-sicuIa seminalis des .Menscbrn mid Ijihl,, ^..n. . I ,.-, r. l.\nat.. Mefle, 1907, \'. 34, pp. 237-1,2.) I.hnnb^. W I- : Tli,- .\„al.a.n .and Physioloj.y of the Se Treatnu.it .a Ih, ,; l.i-Mnv il;o-li.n .\1. and S. J., 1914, V. Th ;,, I; \, and Panioast, II. K. : Observation on the Pathology, Diagnosis and Treat- ment (It Siniinal \,.„uliti5. (.\nn. Surg., 1914, V. 60, pp. 313-18.) \'".-l-l-i illrpl-lberw): Die Samenblasen. 1912. Weis/. l-.: Zn, .\elioIogie und Pathologic der Samenblasenerkra.ikungen. (Wien. med. IXGUIXAL HERNIA.* THE RELATIVE TEACHING VALUE OF ACTUAL PHOTOGRAPHS AS COMPARED TO DRAWINGS. Chas. T. Sm-THEii, M.D.. Cincinnati. The fact tliat one book on hernia has forty-two methods describing the operative cure of inguinal hernia and twenty-seven methods describing the cure of femoral hernia, means that many men are either seeking to have their names apply to their operation or there is some fault to find with most, if not all the methods yet devised. I am inclined to believe, after rather extensive study of the subject, that it is a case of "straining at a gnat and swallowing a camel." Proper application of best known surgical principles to the cure of hernia will result in success and cure of 98 per cent, of the cases. This paper is based on seven years' careful study of hernia, from text- books, cadavers, that I ha\e --een in large clinics, work among my colleagues and personal ojierative experience. I was willing very early in my career to concede that scientific o]ierati\e work for the cure of hernia was much less common than it should be. and that hernia was one of the difficult major operations when considered from all its standpoints. This is self-evident in the face of the well-established fact that until tin- last five or ten years recurrence varied from 5 per cent, to 20 per cent, in the hands of various operators, while at present we can hope for 98 per cent, of cures to follow good work. The student must first ha\ e a perfect and complete knowledge of normal anatomy of the hernia region; he must not only be able to tell it. but be able to demonstrate it on both the cadaver and the living subject. Secondly, he must be able to recognize this same anatomy when the parts are distorted by the pathological conditions found in hernia. I do not want to undervalue drawings, but want to try to show that more photographs in our text-books would be a great advantage in imparting to students (under and post-graduate) the knowledge necessary for them to have to enable them to do a hernia operation in a scientific, anatomic and curative way. -Any surgical condition that is sf) cimimon that it can be found in 6 per cent, of the male ])n])ulation and in 2 per cent, of the female population de- serves the most careful possible teaching. Further, a very small per cent, of students leaving college are able to do a hernia operation properly, and they usually get less able as they grow older, unless they have hospital train- ing or work as an assistant to some capable surgeon. The simple relief of Mississippi VaMey -Medical .\ssociatic ■Clinic, rcbniarv 11, 19U. CHAS. T. SOUTHER 'J Drawings reproduced from Ferguson's Book on Hernia. 1906. Diagrammatic, showing points at which different forms of hernia push through; looking out from within the abdomen. PLATE 2. Di>>section to show location of incision aponeurosis of the external oblique, having tl external ring intact as a landmark. Coi coming out through external ring. Separatic of fibers of external oblique beginning above. strangulated hernia as an emergency is not saying a man really knew what he did, except to replace the gut. Incision for hernia includes (1) the inci.sion through the skin, fat and sujjerticial fascia; (2) aponeurosis of external oblique. The direction and location of these two cuts means much. Skin and fat should preferably be lifted up and either cut with scissors or transfixed with a pointed knife, so as not to wound the aponeurosis of the external oblique at a point that is not desirable. The external incision should be located in the folds of the groin and be ample in length. Dr. Wm. Mayo often makes the assertion in his teachings that skin and fat are only coverings, and limited only by I of specimen showinj vessels, ilioinguinal ne PL.\TE 'ing knot of suture RANSOHOFF MEMORIAL VOLUME PLATE 5. deferens as it passes behi ; cord rcfle internal oblique shi ard; deep epigas- tlie contents within. !n other words, the skin and fat tissues have no re- tentive or curative influence in the oiieration for hernia. The incision in the external obhque muscle or aponeurosis can be made from helow up or from above down ( Bodine and Judd) and far enough from Poupart's hgament to allow of whatever amount of overlapping may be indicated in the given case. The rule is to divide this aponeurosis half way between Poupart's ligament and the rectus muscle or linear semi- lunaris; the external ring can be left intact. This overlapping causes the strain to I)e taken off the internal oblique sutures, and allows more perfect M ^ A ing external obi que incision, dir ection of nni^ cle fibers of inte rnal oblique, sac transfixed, cord. with neck li sated and being deep ep.gast uter pillar of ex ernal Ferguson operation, from his boo ing cremaster muscle to traiisversalis drawing by Miss Cleveland. CHAS. T. SOUTHER union with the internal obhque and (he deeper structures of the canal, meaning cord and transversalis fascia and pedtoneum. Plate 1 is extremely important in enal)ling the student to diagnose the \ariety of hernia with wliieh lie has to deal, and is probably more illustra- tive in a way than an actual dissection cmild be made. It is. therefore, one point in favor of drawings. Plate 2 shows skin incision of ample proportions, a little larger than necessary, except to get a good ])lintograph. Skin and fat are reflected be- low Poupart's ligament and ahoxe to linea semilunaris, giving full view hernia; (1) Double arrow, external oblique reflected; (3) internal oblique; (3) cord; (1) deep epigastric vessels; (.'">) neck of sac ligaled. ready to be transfixed. White lines on internal oblique show direction of muscle fibers. of the entire hernia region and greatly facilitates identification of anatomi- cal structures, making the operation easier and more quickly accomplished. It also shows the location of incision, or rather the point at which the fibers of the aponeurosis of the external oblique are separated, beginning above and going down to the semi-circular fibers that form the external ring. These ring fibers may or may not be cut, or they may be stretched out and nearly or quite obliterated in large scrotal hernise. In a small her- nia don't cut ; in large hernia better cut and overlap for support. If we leave a large leaf in the lower flap of external oblique aponeurosis, we can gras]) it with small forceps or rubber-covered clamps, and wipe off (with gauze) the under surface of the riponcurosis and expose (without RANSOHOFF MEMORIAL VOLUME PLATE 11. iction of drawing from Fergu A'ing Basini operation, with int itched to Poupart's ligament : iture used. effort) the shelving edge of Poupart's ligament, an early and very im- portant step in both the Bassini and Ferguson operations. This usually takes us down to the cord, and the sac will usually be found (in a small hernia) above and slightly internal to the cord. That is, the sac is next to the conjoined tendon, and the cord is ne.xt to the shelv- ing edge of Poupart's ligament, all usually receiving a ciiveriiig from the cremaster muscle. Plate 3 shows external oblique reflected, ilio-inguinal nerve passing over forceps lengthwise and cord reflected inward to show location of shelving edge of Poupart's ligament. Passing transversely over the jaws of the for- ceps are the deep ejiigastric vessels and sheath ligated. Fibers of external PLATE 12. l"eigu> )peration. from his book printed OchsnerS ••Clinical .Sn Suturing inter lal oblique s llg Drawing bv A S. Clevel Pane .;.). CHAS. T. S(U I HFR PLATE 15. Suture knot seen in internal oblique is same lat ligated and transfixed the neck of the sac. [uscle suture is Ferguson's continuous method. ring are intact. Internal oblique muscle is here exposed to a greater extent than necessary in operation. Plate 4. Anatomical, same as Plate 3, with cord reflected down and out, deep ves.sels up on forceps. Sac of hernia has been ligated and trans- fixed well up under internal oblique muscle, as shown by knot of thread, which shows well up on surface of internal oblique. Plate 5. I do not think I have ever seen a plate that demonstrates so perfectly the point at which the vas deferens passes with cord over the deep epigastric vessels. This is important as regards suturing the cremas- teric muscle to internal oblique, as advised by Ferguson. The relative retentive power and influence of the cremaster muscle on the cure of hernia depends on the (1) method of operation and (2) on the A ply approximated PL.\TE 17. lead's operation from Fergus* > tied are holding creniaste internal oblique. Page 5.« RAXSOHOFF MEMORIAL VOLUME size or development of the muscle itself. The cremaster forms (with its fascia) one of the coverings of the sac, while it passes through the inguinal canal. By opening this sac and careful preservation of the cremaster it can be used to cover over the cord and attach to the under side of the con- joined tendon and internal oblique (Halstead). In this method it forms the first step in the suture part of the operation. It is impracticable to use it in a Bassini operation or in cases where the muscle is deficient in development, and has little or no retentive power. The amount of importance given to this muscle by Halstead and Fer- guson and others make us give it a certain definite place in the technique. PLATE IS. (ive interrupted sutui es parsed through lined tendon, under shelving edge of both ends passed through external all knots above external oblique fascia canal. Modified Ferguson operation Plate 6 gives best view of shelving edge of Poupart's ligament, with cord displaced inward. Plate 7 shows method of ligation and transfixion of the sac. which is believed by a number of authorities to he a very important and essential step in the operation. Plate 8 is a drawing by a splendid artist and from Ferguson's book. It was unforunate, in the opinion of the writer, to have so splendid a book as Ferguson's work on hernia so ])rofusely illustrated, and not have a single photograph in the entire book. Page 5.!', CHAS. r. SOUTHER Plate 8 speaks for itself, and for comparison Plate 10 (my own photo) is intended to illustrate what the real operation looks like. Plate 9 is the key to all the photos and is intended only to aid the under- graduate student. Plates 11, 12 and 13 are rejjroductions of draii'iiu/s from Ferguson's book and are described under each cut. Plates 16 and 18 are illustrative of what seems to me an advantage in placing the sutures holding the internal oblique {conjoined tendon) over to Poupart's ligament. These sutures are placed as mattress sutures, begin- ning by passing the round-pointed half curved needle from without through the lower flap of external oblique aponeurosis just above Poupart's liga- ment, then from without in through internal oblique (conjoined tendon), while the same is held upon finger, then from within, out under Poupart's PL.XTE 19. Drawing by A. S. Cleveland. D show HaLstead technique, i f rectus when internal oblii 'rom Ferguson's book. ler M. lirodel. PIRATE 20. Showing three rows of sutui oblique fascia overlapped the second and third row of sutur: ligament, coming out on top of the lower flap of aponeurosis of external oblique fascia. Overlapping the External Oblique Fascia. — This can always be done, provided the primary incision is properly placed, namely, midway between Poupart's ligament and the linea semilunaris. When the external oblique fascia is overlapped (see Plates 20 and 21), it takes up the surplus in the tissues, and by putting more tension on fascia causes the linea semilunaris to be drawn nearer Poupart's ligament and relieves tension on internal oblique and conjoined tendon, thereby facilitating union of the deeper struc- tures. This carries out the most accepted surgical principles advocated by the best authorities in the treatment of all forms of ventral hernia, namely, overlapping the fascia. Suture Material. — Consensus of opinion among the big operators is so greatly in favor of animal ligature that wire, silk, linen and silk worm Page Mr, RANSOHOFF MEMORIAL VOLUME gut will not be considered. The opinion of Coley, Ferguson, Judd and the late W. T. Bull must be accepted until disproved, and they all use catgut, some chroniicized. some plain. Most of them favor a twenty or thirty dry chromic gut, never larger than a No. 2, and Ferguson favors No. 1. Interrupted sutures have the greatest number of advocates. 'I'hree knots should be put on each of the deep sutures, including muscle and Pouparl's ligament. For lapping the fascia No. chromic gut may be used. A heavier plain or iodin gut has many advocates. Never put a tension on sutures, and never tic tight enough to obstruct the blood supply. , Suppuration is constantly jiresent in all wounds where sutures are tied tight enough to stnp ibc blood supjily. Tissues zcill die :^'hen strangled. 1 belie\e that more returns and more infected wounds in hernise are due to putting the sutures too tight than all other causes combined. This is particularly true of the skin suture. Some form of non-absorbable suture is best for the skin, but should be removed from fifth to tenth day. How- ever, if there is no tension and tissues are carefully approximated with silk worm gut, silk or linen, either by subcuticular stich or Glover stitch, the suture material will do no harm for ten days. However, the skin suture has done all the good one can hope for in six days, and union will be more rapid if it is removed at this time. It is claimed by many that a double strand of No. 1 chromic catgut is preferable to a heavier suture material, used single. ']'he present tendency is all toward the smallest possible ligature that will hold, and No. 1 has been ample for most operators. Personally I have used nothing heavier than No. 2 for any kind of work for years. Page 536 CHAS. r. SOUTHER In order to tie the knot tightly and not strangulate the tissues, make the first knot easy or loose, and then insert the point of artery clamp under the knot, and tie second and third knot as tight as suture will stand, then remove the force])s, and tissues will not be strangulated. The writer has favored the antamic operation of Ferguson for several years, l)ut has been perfectly willing to give equal merit to Rassini's method on account of the large number of operators who favor it. Bull and Coley and others are warm advocates of Bassini's method. If the student will study Coley 's and Ferguson's writings, and take the liberty to read a little between the lines, he will see that they do not differ greatly. Coley calls it Bassini's operation with or without transplantation of the cord. Coley's writings have been more especially of hernia in child- hood, at which time cure is less difficult. Disposition of the Sac in Hernia. — Quoting from a recent paper on this subject (C. T. S., Lancci-Climc. October 6, 1909, Deansley, British Medical Journal). I believe that effectually removing the sac cures 95 per cent, of cases of hernia. Macewen lays great stress on complete removal of sac by ligation and transfixion under internal oblique (Plate 7). Ball (by Ferguson) removes the sac alone in children, and says sutures are i.ot necessary 'mless cough is present. Colev says the sac is largely congenital, and its removal is best in all v-ases Ferguson says the congenital deficiency in the internal oblique plays an important part in the etiology, but he always removes the sac. The consensus of opinion from the recognized authorities on hernia may be taken in abstract as follows: Hernia has a complete sac except in the sliding form, which is rare, but should be borne in mind always. Removal of the Sac by .'iutitre. Ligature or Obliteration. — Sellenings (American Journal of Surgery. March. 1909) claims to have gotten his idea from Matta's treatment of aneurismal sac obliteration. It has been settled beyond a question of doubt that a peritoneal lined sac can be trans- formed into fibrous connective tissue by proper treatment. Nature proves this by the fact that we all do not have hernial sacs. R. C. Coffee and others have been instrumental in bringing out the clinical proof of same ; yet removal and ligation with or without transfixion is the most accepted 'method today. So important is this care of the sac that in femoral hernia (small variety) removal of the sac with its proper transfixion will cure hernia of the femoral type, even though we do not close the femoral canal (Ochsner). This same assertion holds good in the treatment of inguinal hernia of early childhood, prior to five years (Ball and E. K. Herring). The transfixion of the neck of the sac is advocated by Macewen, Butler, Halstead, Ferguson, Lanphear and others ; yet in the light of the role it RAXSOHOFF MEMORIAL J-QLUME plays in femoral hernia, I do not believe it has been sufficiently emphasized. Treating the stump by this method changes the point of greatest intra- abdominal pressure and greatly facilitates cure. It removes the infundi- buliform process of peritoneum and prevents a continuation of the intra- abdominal pressure at this point by obliterating the depression at the in- ternal ring. The probability of hydrocele developing is greater with Bassini's opera- tion than with Ferguson's. \Mien the distal portion of the sac is left undisturbed, the upper end where it has been severed from the neck .should be anchored with small, plain catgut to the cord, and never ligated. This prevents formation of hydrocele to a great extent. My own impression and practice has been to ligate at neck, well up under distal border of internal ring, and cut off. The distal portion of sac may be removed if the hernia is acquired. Distal portion may be left in position when hernia is congenital, that is, when sac is continuous with the tunica vaginalis testis. This point should be determined at once when the sac is opened, and treatment instituted accordingly. The abo\e is sub- ject to some modification when sac is large, thick and old. and it may be treated as individual operator likes. In further consideration of congenital hernia sac is best treated by Doyen or Bottle's operation for hydrocele. ( Recently published as new by E. \\". Andrews, Chicago, Annals of Surgery, 1909.) Simple eversion around the testicle and one stitch put at the top ; this absolutely cures and prevents any possible formation of liydrocele without the time-consuming element of removal. I always transfix the ligated neck of sac up under internal oblique muscle. Contents of sac can be returned to abdominal cavity in all simple un- complicated cases. Resection of intestine and excision of incarcerated omentum are at times necessary in strangulated forms of hernia, but can not be treated here. A good way to test the re-establishment of the circulation is to re- place a doubtful piece of gut into the cavity after ha\ing passed a heavy long suture through the mesentery under the gut. so the same gut can be reinspected before closing the hernia. This relief of tension is frequently followed by a return of the color and normal circulation. When the gut can not be replaced without undue pressure it is best to enlarge the ring, or make a second incision above and pull the gut back from within the cavity in femoral hernia. Charles Harrison Frazier, of Philadelphia (Annals of Surgery, Octo- ber, 1911, p. 555), shows the only cut I have ever seen illustrating the mat- Page S3S CHAS. T. SOUTHER tress suture for the interal oblique and Poupart's ligament and external aponeurosis which advocates the tying of the sutures all external to ex- ternal oblique. This was published after the completion of this paper. Rose and Carless "Manual of Surgery." 1907. contains a cut illustrating what Frazier brought out, but no emphasis is put on it in the text. 1 have tried to understand what the other fellow has tried to teach, and have tried to present the advantage that the photograph has over the draw- ing, or at least that it should have a more prominent place in the teaching of hernia than it has formerly occupied. TOXICITY (IF URINE IN PREGNANCY.* rr W. Stkw. Ci In the year 1897 the writer made, with tlie urine of pregnant women, i numlier of experiments on rabbits with the object of determining the toxicity of such urine. The great variabihty in results which \'o!hard' had obtained when going over the work of Ludwig and Savor,- Tarnier and Chambre- lent,^ Bouchard^ and others seemed to justify the conchision that the in- travenous injection into the circulation of so foreign a fluid as urine was open to grave objection, especially as Volhard found numerous cases in which thrombosis was a decided contributing factor, if not tlie principal one, in the production of death. The writer's experiments were made with urine which had been collected under what was supposed to be careful asepsis, over boric acid. This urine was concentrated, filtered, neutralized and in- jected warm into the abdominal cavities of rabbits, in tlie proportion of 80 to 100 c.cm. to kilogramme of animal. The following experiment shows the character of the work done : "Experiment VII — May 13, 1897. — Urine of a primipara (Kramig) aged twentv-one years. Specific gravity. 1,01."); acid; no albiunin ; no sugar. Woman always healthy ; well developed ; date of expected confinement. June 29, 1897. Family history : Father died of heart disease ; mother healthy. No diathetic condition discoverable. This urine was boiled down to one- third of its bulk, to specific gravity, 1,056; fifty cubic centimeters of this concentrated urine were neutralized, filtered, warmed and injected into ab- domen of a rabbit weighing 1,750 grammes, in fifteen minutes. 4:00 p. m., returned to cage ; can not support himself ; lies flat on abdomen ; makes effort to regain his feet; respiration slow; supports head against side of cage. 4 :07 p. m., has convulsion, tonic followed by clonic spasms, opisthot- onos ; pupils contracting ; breathing in short gasps ; lies on side ; can not be arou.sed; palpabral reflex absent. 4:10 p.m., stretches himself every thirty seconds (about) ; these attacks are undoubtedly convulsive; during interval is quiet. 4:18 p.m., attacks come on regularly and are accompanied by a peculiar grunting sound. 4 :24 p. m., the last attack was of longer duration than the others ; the abdominal muscles are contracted ; the front and hind legs are drawn together ; the fore legs tremble while the hind ones move up and down. 4:28 p.m., panting; mouth open; stretching precedes the convulsive attacks, which are becoming more marked. 4:30 p.m., violent convulsion ; death. "Post-mortem examination, eight hours after death; fifty-five cubic cen- timeters of amber fluid of specific gravity of 1,022 found in abdominal cav- ROBERT JV. STEWART ity; abdominal vessels injected; organs normal in appearance; post-mortem discoloration of abdominal wall on left side."" The convulsions which are described were found in almost every case, and simulated so closely the convulsions of strychnia poisoning or of puer- peral eclampsia that there seemed to be no reasonable doubt that the urine of pregnancy contained deadly poison or poisons, and that the method of injection made no appreciable difference. It seemed further justifiable to conclude that the poison was very soluble, was not aft'ected by heat, and that it was a constant ingredient of the urine, because the mortality was 100 per cent. During the year 1897, after the results of the foregoing experiments liad been published, new experiments were made under the same methods, brt upon both rabbits and white mice. The urine was used concentrated and unconcentrated. "The mortality was again nearly 100 per cent. The figures are as follows : Unconcentrated urine taken during the last month of preg- nancy killed seven rabbits and two mice, one mouse recovered; when con- centrated it killed two mice and failed with one ; when taken during labor, unconcentrated urine killed one rabbit and one mouse, and spared none ; when taken post-partum, the unconcentrated killed two rabbits and one mouse, and failed with none."" The method seemed good for rabbits and white mice, and no difference could be detected between concentrated and unconcentrated urine. At this juncture, 1898, Dr. F. Forchheimer suggested that we carry on a new line of work, the urine to be taken not only from pregnant women, but also from patients who were suffering from various forms of intestinal auto- intoxication. The results of this joint work were published in the American Journal of Medical Sciences, September, 1899. The special work which the writer did in connection with Dr. Forchheimer was published, together with .some new experiments, in the American Journal of Obstetrics. \'ol. XI. No. 3, September, 1899. The mortality in this special work agreed so closely with that in our joint work that the writer can show what that work was l)y quoting from his own paper. "The method in detail was as follows : Women were to Ijc near term ; the genitals to be thoroughly cleansed with soap and water ; the urine to b'.' drawn by sterile catheter into sterile Erlenmyer flasks, which were cotton- stoppered before and after filling; the urine to be immediately boiled and then sent to our laboratory and injected (this was usually done at once, sometimes twelve or more hours later) ; injections to be made intra-abdomi- nally under same precautions as heretofore, except that the urine was neither neutralized nor filtered. Experiments were made on six rabbits and twelve mice with urine taken from eight women. The proportions used were about the same as those of the previous experiments (80 to 100 cubic cen- timeters to kilo) ; a mouse received 25 minims, as a rule, but in four in- stances 50 minims were injected into these animals. All of the animals P^gc o'll RAXSOHOFF MFMORIAL VOLUME lived except one mouse, which had received 50 minims ; it died in twenty- four hours. The mortahty was, therefore: Rabbits, nothing; mice, 8 per cent. In addition to these, four other experiments were made on mice with urine taken from women in labor, and one with that of the post-par- tum period. All of these mice recovered. Three other animals, one rab- bit and two mice, received injections of urine which was twenty-four hours old; all died. If these experiments be grouped in classes, it will be found that of urine boiled at once and used within twenty-four hours the figures stand: Seven rabbits and nineteen mice experimented upon, of which six rabbits and sixteen mice recovered, a mortality of rabbits, 15 per cent:; mice, 16 per cent.; all animals together, 15-(- per cent. Mortality after urine has stood for twenty-four hours, 100 per cent."" The new experiments to which reference has been made were made to test this method. As stated in that paper, "I used unconcentrated urine from seven women, the majority of whom were in the last month of preg- nancy, the others in the post-partum period. The results show that fresh, unboiled urine killed one mouse out of five, or 20 per cent.: while fresh boiled urine killed two mice out of nine, or 22 per cent. ; that the same unboiled urine, after standing for twenty-four hours, in cotton-stoppered, sterile flasks, killed all five of the mice, or 100 per cent. ; while boiled urine which had stood for twenty-four hours in similar flasks killed four out of five mice, or SO per cent." The experiments of the early part of 1859 agreed with those of Dr. Forchheimer's so closely in regard to mortality that there was good reason to believe that some carelessness in the collection of the urine must have caused the increased mortality in the experiments which are quoted in the preceding paragraph. The writer decided to again test the question, and to include, at Dr. Forchheimer's suggestion, the question of the probable action of bacteria in the production of the poisonous substances which were evidently in the urine. In accordance with this decision and sugges- tion, a new line of experiments was begun in the early months of 1900. The method was along the lines pursued in the more recent work, but dif- fered not only in the greater care which was used, but also in the particu- lars which are mentioned below. The details are : The urine was drawn ofl^ by means of sterile catheters into sterile cotton-stoppered Erlenmyer flasks at about se\en o'clock in the morning, the external genitals of tho patient having previously been carefully scrubbed with soap and water, then bathed in lysol solution (dr. 1 to Ol). and finally washed off with sterile water. Especial care was given to the meatus urinarius. Stress was laid upon the instruction that the urine was to be the accumulation of the night as nearly as possible. Only one catheterization was permitted, and the urine was drawn oft' in nearly equal quantities into two flasks, the con- tents of one of which were to be immediately boiled. The urine was taken from pregnant and puer])cral women. This urine was injected intra-ab- ROBERT IV. STEWART dominally into white mice in quantities of from fifteen to twenty-five minims to the animal. The greatest care was demanded that surgical asep- sis be observed in all manipulations. An ordinary hypodermic syringe was used, the needle of which was pointed downwards to avoid wounding liver, heart or other organ. Boiled and unboiled urine was injected into individual mice on the first, second and fourth days, or more definitely within twelve, thirty-six and eighty-four hours of the catheterization. At the time of making the injections, plate cultures were made on gelatin or agar-agar. Nine series, or forty-eight experiments in all, were made with urine taken from seven women. In seven of the series the urine was taken dur- ing the last month of pregnancy, and in two from the i)ost-partum period. The women were all healthy, never showed any symptoms of eclampsia, nor any evidences of kidney or bladder trouble. Forty-eight mice were used. Forty recovered and eight died. Of the eight, six died after injections of unboiled, and two after boiled urine. The two last-mentioned mice probably died from causes which had noth- ing to do with any poisonous properties which the urine may have pos- sessed. One died in five days, undoubtedly from asphyxia, as its air supply was cut oflf by the inadvertent covering of the jar in which the animal was confined ; the other died in ten minutes without convulsive action, probably from injury to some organ. These probabilities are strengthened by the fact that unboiled urine from the same catheterization and used at the same time did not kill the mouse. This explanation is made because if these two mice be included in the tables, the mortality rate is 16% per cent, (eight in forty-eight), while if they be excluded, the rate js reduced to 13 per cent. + (six in forty-six). With this explanation it is thought best to include the animals referred to in all subsequent deductions. The details of the mortality are shown in the following tables : Unboiled I-IUST U.W UKINIC (3 to 12 hours) Re covered 8 5 7 5 S Died 1 Boiled . . ^ C '-""1 Unboiled SECOND IMV URINE (27 to 36 hours) 2 Boiled Unboiled . . fOUKTU DAY URINE (75 to 84 hours) ^ Boiled RAXSOHOFF MEMORIAL VOLUME If the position which was taken in reference to the two mice that died after injections of boiled urine be tenable, the mortality from boiled urine was nothing, while that from unboiled urine was: First day. 11 per cent.; .second day, 28.6 per cent.; fourth day, 37.5 per cent. It is an interesting fact that in those cases in which the urine was used both before and after delivery, no essential difference was noted, for the reasons that in one case all of the mice recovered, and in the other two mice died from causes not referable to poisonous action, the two to which refer- ence has already been made. Twenty-seven of these mice were used for ex- ])erimental purposes for the first time, and twenty-one had been used before. Of the former, twenty-four recovered and three died; of the latter, sixteen recovered and five died. Two of the fresh mice should not be included for reasons already stated, a fact which makes the mortality in fresh mice one in twenty-five, or 4 ])cr cent., while that of mice which were used more than once was five in twenty-one. or nearly 24 per cent. This fact would seem to be conclusi\e that repeated injections did not produce immunity, did not lessen the sUscejitibility. CULTURES The following table shows the number of cultures made, the day upon which they were made, kind of urine used, and whether the culture w-as made upon gelatin or agar-agar.' IIKST i>.\v C.cdatin .\gar-.\gar Unboiled 6 3 LSoiled 6 3 SlX'ONl) D.W Unboiled 4 3 Dniled 4 3 Unboiled 4 3 Boiled 5 3 These cultures were examined in twenty-four and forty-eight hours. The presence or absence of growths is shown in the follc\\ ing tables: (ledatin .\gar-Agar 6 6 2 L-nboilc 10 min. hours Unboiled ISecond Day Unboiled IFourth Dav 1 .\uiiierous colonies Sterile 24 hours; nume ous colonies 3rd day 12 hours "Loaded" in 24 hours. '12 hours 1 Loaded in 48 hours. 18 hours Loaded in 24 hours '24 hours The first three specimens were from the same patient. Nos. 1 and 2 was taken nine days before delivery, and Xn. ,^ twelve hours after de- livery. The next three specimen> were all taken about six weeks before delivery from the same patient. Two control experiments were made from urine laken from the saine patient at the same time, but which was not used until the fourth day. Both mice recovered, although the unboiled urine showed two hundred ( ?) colonies and the boiled urine was sterile. The last two specimens were taken from same patient less tlian four weeks before delivery. ROBERT W. STEWART In not one of these mice was there any macroscopic evidence of peri- tonitis or injury to the abdominal organs. In Nos. 1 and 3 nothing was found microscopically in the blood. These are the mice whose deaths were attributed to inanition and injury, respectively, as has already been ex- plained. In No. 2 rather large bacilli were found in the blood ; in No. 4 small ovoid bacilli were present ; in Nos. 5 and 6 the bacilli were large : in Nos. 7 and S diplococci were found. Unboiled urine was injected in all those cases of death in which septi- cemia was diagnosed, or in which micro-organisms were found in the blood, and it, therefore, is a fact of considerable significance that the boiled urine, which was drawn at the same time as the unboiled, and which was injected at the same time, did not kill in a single instance. As far as could be ascertained none of these mice had convulsions before death. This is largely surmise, however, because in most cases the animals were found dead. In the few cases in which the death struggle was observed no convulsions occurred. If all this work be taken in review it will be seen that urine collected — that is, passed by patient over boric acid — evidently contains a convulsive poison which is deadly in 100 per cent, of the cases, to rabbits and white mice, whether the urine be concentrated or unconcentrated ; that when the urine is drawn by catheter under strict surgical asepsis, the mortality is greatly reduced, and that when the urine is so drawn and immediately boiled the mortality is practically nothing. This contrast at once suggests the pos- sibility of error in the deductions which have been drawn by investigators who have used the boric acid method, a method which has undoubtedly been followed when the urine is sent from any distance, or has been allowed to stand two, three or four days before use for experimental purposes. Even in the writer's work asepsis plays the important role, because in the early ])art of 1899 the manipulations were made practically under his supervision, and the mortality was reduced to 16 per cent., while in the latter part of the same year the drawing of the urine was not done by his own assistants, consequently could not be so carefully supervised, and the mortality rose to much greater proportions. The experiments of 1900 were again under his direct care and the mortality fell again to the figures of the early part of 1899. Forchheimer's individual work confirms this statement. The relation of mortality to sterility or infection of the urine at the timr of the death of the animal is very interesting. The table shows that two specimens of boiled urine which were sterile at time of injection and remained sterile afterwards, killed mice — the two which have been excepted throughout these tables ; two specimens of fresh urine showed no growths in twenty-four hours, but developed numerous colonies in the succeedings days; three specimens of fresh urine were con- taminated within twenty-four hours, and one in forty-eight hours. In other words, all of the fresh urine which killed mice must have contained micro- RAXSOHOFF MEM0KL4L VOLUME organisms at the time of the injection, and in every case septicemia or the presence of bacilH could be demonstrated in the blood. It is reasonable to suppose that these organisms either existed in the blood of the mothers, in their laladders, or were introduced into the urine during the manipulations. The women were all healthy, had no fever, nor other systemic disturbances, no anorexia nor local deviation from the normal, and consequently could not have had blood so saturated with bacilli as to infect the urine. The ab- sence of epithelium, albumin, blood and pus cells and the freedom from pain on urination, prove there was no cystitis. As the source of the contamination there is left, then, only the manipulations. This position is strengthened by the fact that the septicemia could not have been due to the presence in the blood of these animals of bacilli which only became virulent because of the injection, for the simple reason that numerous other animals had been kept in the cages with the ones which died, had gone through the same process of experimentation and yet recovered. Therefore, it seems to the writer that any other view of the cause of death than infection of the urine at the time of catheterization or during some of the subsequent manipula- tions would be illogical and strained. Not that the writer means to imply that imperfect oxygenation of food or tissue metamorphosis, with consequent production of uric acid, carbonic acid, paraxanthin and the xanthin bodies generally, may not mean the poisoning of the system, as has been claimed by so many distinguished authorities. Nor is he willing to say that these substances are not thrown out of the system by the kidneys. Above all, he does not wish to be under- stood as claiming that bacteria are the sole cause of death in the animals which have been used by other experimenters. At the same time one can not deny that, as far as the present work goes, there is good reason for believing that what has heretofore been attributed to poisons generated in the human body was often due to micro- organisms which must have been introduced into the urine after it was voided. The one claim which Forchheimer and the writer do make is that the methods, and consequently the deductions of other experimenters, are open to serious objection, and that the intra-abdominal injection of urine which has been drawn by catheter under strict asepsis is freer from objection than the intravenous method. Finally, while the writer is diffident in claiming too much for the elifect which bacteria may produce in this line of work, it is a significant fact that in his own cases 75 per cent, of the deaths can not be attributed to any other cause than bacteria. Note — Dr. .\llan Ramsey did the bacteriological part of this work and materially assisted in all of it. He deserves the credit and has my gratitude. LITER.-VTl'RE. 1. Volhard: M. . ,1 . h, f (,,li u. Gyn., Bd. V. 1S9T. 2. Ludwig. IK ^.1 . \1 ,,,!,, In. f. Gcb. u. Gyn., Bd. I, 1S05. ■ 3. Tarnier el ( li.unl, , l> n. : >,.,•. d.Biol., 1SU2, No. U. 4. Bouchard: "".Vulu liiluxi^,ilu.ii." 5. Stewart: Amer. 0. Stewart; Amer. Page 5j8 T?1E EARLY DIAGNOSIS OF SYPHILIS AXD A COMPARATIVE STANDARDIZATION OF THE TREATMENT.* E. r,. Tauiuck, ^r.D., Cincinnati. In the problem of syphilis it is im])erative to secure an earlier and more efficient diagnosis of the disease than is the case at the present and a more generalized effective treatment. 'J'his should lie the keynote of our endeavors. The early diagnosis of .syphilis is an unknown quantity to many men who are practicing medicine in our times. To men who have the older ideas of the disease to guide them, ideas that are firmly planted in their minds by a couple of decades of practice, it seems almost sacrilege to insist that waiting for secondaries is a criminal action and that we lose the benefit of the one psychologic moment in the life history of syphilis when we can seize our real opportunity. The definite diagnosis in the early primary stage before the spirochete has spread to the lymphatic system near the primary lesion and before the serologic reaction is positive is the one and only time that, taken advantage of, may lead to success, and it is the time for action instant and effective. This is the time for radical cure if such is possible. An injection of ars- phenamin here can put an immediate end to infectivity of the case. A sterilization complete and entire seems possible here. The suppression of the biologic and serologic evidence of the disease is possible and may be probable here. This should lie our treatment for paresis, tabes dorsalis, iritis, etc. PROPHYLAXIS OR TRF.ATMRXT THAT WILL PRE\'EXT THESE COXIDI- TIOXS The first week or so of the initial lesion, while syphilis is still a local condition, is the time that we should emiiloy every energy and endeavor of our diagnostic and therapeutic armamentarium to cure, for never again in the picture of syphilis for the individual patient or the state will this moment return. Our public health services, medical colleges, hospitals and clinics must teach this point and ever impress it on all in contact with them ; that is, the student groups, the nursing groups and the public in general, these facts and necessities. The dark field examination must he a routine at the clinics, in the hos- pitals and in our private practice. The organism must be known and recognized by all. nbei- 29, 1919. KAXSOHOFF MEMORIAL VOLUME The newer staining methods, such as the MedaHa method, must be taught generally. There can be no valid objection to teaching the profes- sion of the future and the present the only means of diagnosis for the period when the dangerous sequehe may be mastered and dominated by us. Every sore, whether on the genitalia or elsewhere, is or should be open to a suspicion of chancre and should be repeatedly examined for Spiro- cliacta pallida. Every papule, nodule, crack, excoriation and herpetic or other erosion should be viewed with the possibility of an initial lesion and should be examined for Spirochacta pallida. Chancroids should not be accepted as uncomplicated with syphilis; double infection is always pos- sible. .\ntiseptics applied, especially mercurial^., make tin- finding of Spiro- chacta pallida diflicult or almost impossible, and because of this we should teach that no mercurial dressings, or better still, no antiseptics, should be applied to any lesions until the examination for Spirochaeta pallida has been made, and if any have been used, it should be made a routine to irri- gate thoroughly with physiologic sodium chlorid solution and to apply a wet dressing of the solution for twelve hours or more before examining for Spirochacta pallida. To obtain Spirochacta pallida, a definite method is important. We have used in the Cincinnati General Hospital this method: The surface of the lesion is wiped with a cotton sponge to remove superficial organisms. The wound may be rubbed or teased lightly, but one should not cause bleeding; just an oozing that will give serum to trans- fer to a new clean side and slip should be produced. Immersion oil is put on both the under surface of the slide and upper surface of the cover. This will give a continuous airless medium from dark field to objective. A focus with fine adjustment should be secured until one gets a dark background with the glistening moving particles in white rings. Then a search for the twisting spirochetes may be instituted. ^\s a professional body, let us be honest and acknowledge that we have not spread the vital importance of early diagnosis. It has taken a world war to impress on us that the modern conceptions of syphilis have not been taught in our medical colleges. We have zealously striven to white- wash the episodes occurring in the wrecks due to this disease. We have had clinical characteristics and endless discussions as to secondaries and tertiaries and neurosyphilis, forgetting that we were proving our guilt in this very manner, and now we must scrap our clinical dififerences and turn to laboratory diagnosis to the finding of Spirochacta pallida. I do not mean here the serologic diagnosis, for then we are losing our great oppor- TR.MXIXG THE PROFESSION TO E.\RLV DI.\C-XOSIS How can we create this? This is our tremendous duty. You must all aid this. We must aid all the men who will do dark-field work in the E. B. TAUBER smaller towns and villages and show them and others by our support that Ave are back of them. The internists, the surgeons of the smaller localitic- must call on the man in that locality who has special knowledge of syphilis, and this will cause the demand to be supplied. We must send to Coventr\ the man who cauterizes or applies some medicament to the sore on the penis or other location before advice, and competent advice at that, is given and the dark-field tests are made. In early .syphilis, systematic treatment must be immediate and nui.^t be pushed vigorously ; sledge-hammer treatment here is indicated, not feather- duster types of treatment. vSyphilogra]:ihers will doubtless agree that the efifective time for arsplienamin is early, before the serologic tests are posi- tive. So, then, this places on us the burden of outlining a method or scheme for treatment that shall be more or less standardized. Here I mean a treatment for the majority of cases, not for individual ones; also a treat- ment that will not be inflexible but one that has been tried- over a long period of time in a sufficient number of cases to at least have the merit of being successful. The outline I wish to submit has been tried at the Cin- cinnati General Hospital, the outpatient dispensary, the night venereal clinic and in my private practice, all of which I have under my control, and our results have been very good. Our method is as follows : A SUCCESSFUL METHOD OF TREATMENT Courses of from four to six intravenous injections of arsphenamin of from 0.3 to 0.6 gm. at intervals of from three to seven days are given, com- bined with mercury. Here we may with one or two such courses eft'ect a cure. But even with such vigorous treatment a second or third course of arsphenamin of the same type is advisable after a two months' interval, given with the same courses of mercury. In all cases, after the Wassermann test is positive, I believe at least three such courses of l/ofh arsphenamin and mercury to be the minimum, and more can be given as indicated. I believe that mercury, given either by intramuscular injection.s ol solulile or insoluble preparations or by rubs, is of great aid to our arsphenamin therapy, and in the rational cure of syphilis, mercury and arsphenamin must be combined. The courses of mercury should be from ten to twelve injections, at weekly intervals, of an insoluble; or from twenty-four to tliirtv, given every other day, of a soluble, or thirty to forty daily inunctions. T nivseh believe in giving one course of each type of mercury with each course of arsphenamin. Serologic tests should be made once a month at first, and later at two month intervals, until the test seems to become permanently negative as shown Ijy at least five unbroken negative tests, each six months apart, with no treatment and no clinical evidence of syphilis before we should become in the least optimistic in regard to the case as being checked or cured. RAASOHOFF MEMORIAL VOLUME It is my opinion that provocative injections and spinal puncture with the colloidal gold test may be made; but there is a difference of opinion as to this need, except in cases that require these special methods. Tn late syphilis, mercury and iodids should he ])Ushed in courses with arsphenaniin given in the same way. In secondary syphilis, the first year, three courses as above outlined of from six to eight doses of arsphenaniin in each course, combined with mercury, and not less than three of such courses are indicated. The second year, if the Wassermann test remains positive or there is recurrence of any lesion, practically a repetition of the first year's treat- ment, as outlined, will be necessary. If the \\'asserniann test is negati\e and remains negative and there is no recurrence of lesions, at least four doses of arsj^henaniin in conjunc- tion with two courses of mercury arc recommended. The third year, if the \\'assermann test remains negative and there have been no recurrences from the first year, a patient should pass into a period of observation with regular periods for a serologic examination. If there is any nerve involvement or tabes and paresis, the treatment will depend on the individual case and will be cavered by any general methods ; but treatment must be pushed for years. Congenital or hereditary syphilis requires longer and more persistent treatment ; but again more individual treatment is necessary and cannot be outlined in the same way that early acquired syphilis can be. To re- capitulate, my outline is as follows as regards standardization for early .syphilis : Arsphenaniin and mercury to be given combined. Arsphenaniin. each course from four to six doses of from 0.,i to 0.6 gm. intravenously at three to seven day intervals. Mercury (insoluble), gray oil, mercuric salicylate, twelve doses at weekly intervals, dose from three to five minims. Mercury (soluble), twenty-four to thirty injections of mercuric cyanid or mercuric chlorid, given every other day. Rubs, twenty-four to thirty given every day. First Year. — First course of treatment, from two to two and one-half months. Rest, one month. Second course of treatment, from two to two and one-half months. Rest, two months. Third course, from two to two and one-half months. Second Year. — If Wassermann is negative, rest after tiiird course for four months; mercury, two months; rest, four months; mercury, two months. If Was.sermann is positive, rest, two months; course of arsphenaniin and mercury, two months; rest, two months; arsphenaniin and mercury, two months; rest, two months; arsphenaniin and mercury, two months: E. B. TAUBER Third Year. — If W'assermann is negative, patient passes to period of oljservation with regular serologic examinations. If W'asserniann is positive, rest after last course, two months; arsphena- niin and mercur}-, two months; rest, two months; mercury course, two months; rest, two months; ars])lienamin and mercury, two months, and so on, heing controlled hy serologic findings. It is not easy to state when a cure is accomplished; hut, in general, we can only say, by intensive therapy safety can be secured and in most cases a cure can be effected. This may result in overtreating in some cases, but it is better to err in this way than to undertreat a single one, and some cures require a definite amount of treatment on a definite basis, if the needed results are to be obtained. Therefore, before patients are told they are well, even after repeated negative Wassermann tests without treatment { for negative Wassermann tests during treatment only indicate that progress is being made), I consider it necessary that at least two or three years of negative serologic tests w-ithout treatment or recurrence of any symptoms indicative of syphilis shall elapse before we can even say that we think the pathologic condition is eliminated. In so brief a paper I could cover only majority cases, and no attempt has been made as re- gards treatment or outline for individual cases. COXCLUSIOXS 1. Xo single sign of improvement should be accepted as definite or fmal, and treatment should not he stopped at such indication. Only cessa- tion of all around symptoms is indicative, and that only if it continues through years. 2. Arsphenamin therapy is necessary, since it controls infecti\ity and contagion. It yields quick results. 3. Mercury is essential but as a splint to our arsenic therapy and as an aid to permanence in cure. 4. Most syphilis is undertreated. Sledge-hammer blows are indicated. Overtreatment is to be preferred to undertreatment. 5. It is better to be overconservative rather than optimistic in staling that a cure has been effected. Our modern therapy is still in too infantile a stage to justify anything but overconservatism. I believe that specializing and efficiency tendencies can be obtained, and very ably, in the treatment of syphilis. Hospitals and clinical centers in our larger cities can be used by smaller centers. The extension of war-time methods in the army to civil practice will and should come. In a few words, I bclie\-e syphilis is as easily prex'entable as other in- fectious diseases. With syphilis an actual condition, it must be recognized RAXSOHOFl- MEMORIAL VOLUME early and treated early if its economic results are to be prevented. Thu-^ our problem is early recognition and early treatment. The early period is its period of greatest transmission ; al>o the period in which our chances of curing a patient are greatest. This places the burden squarely where it belongs, on us, the medical profession, and also on the public health service, medical schools, hospitals and clinics. These different agencies must individually disseminate knowledge, acquire competent teachers, and adequate equipment to give adequate treatment and to graduate competent physicians. This means that syphilis needs centralization, efficiency, con- trol, and the teaching of the early diagnosis of syphilis and a comparative standardization of its treatment. INHALATION EXPERIMENTS ON INFLUENZA AND PNEUMO- NIA, AND ON THE IMPORTANCE OF SPRAY-BORNE P-ACTERTA IN RESPIRATORY INFECTIONS.* WiLLiAjr B. Wherry and C. T. Buttf.rfifxd. Cincinnati. While the influenza viru.s appeared to be of reduced virulence during the outbreak of February and March, 1920, the occasional occurrence of a family outbreak, or of rapid death due to pulmonary edema, seemed to in- dicate that it was identical with that present in the outbreak of 1919. We feel particularly sure that we were dealing with cases of influenza in- the family of S., because the mother, father and eight children all came into the hospital at once. Most of these ten patients had bronchopneumonia and one purulent pleuritis. Cases R. and S., B. and B. and T. were of a milder type, although B. and T. had secondary bronchopneumonia. These cases were chosen because most of them had been ill for only a day or two at the time the material was collected. Thirty-eight cases, including those just cited, were examined bacterio- logically. All aerobic, partial tension and anaerobic blood cultures were negative. For the throat and sputum cultures we used + 0.5 agar con- taining 5 per cent, of rabbit blood. Incubation was at 37 C. under aerobic, partial tension and anaerobic conditions. B. influenzae was isolated from twelve cases. Six of the twelve were from the family S.. who all became ill at once. From the father of this family we failed to isolate B. in- fluenzae, and he was ill for months with streptococcus empyema. In six cases B. influenzae was the predominating organism and in four it was present in pure culture. When B. influenzae was grown at partial tension it retained its minute bipolar form and showed less tendency to involution than when grown aerobically. All the strains were strictly hemoglobinophilic while the Koch-Weeks bacillus was isolated on aerobic, partial tension and anaerobic slants of ascites agar, and could be subcultured on this medium. All strains failed to produce indol in hemoglobin broth when the sulphuric acid-sodium nitrate test was applied. However, the growth in our broth was scanty. Most of the associated bacteria belonged to the pneumococcus, hemolytic streptococus and staphylococcus groups. No colonies that might have represented the B. enteritidis (type M 5), which appeared in the sprayed animals, were noted, and it is not likely that they were overlooked, for M r> colonies on blood-agar plates at partial tension are a \ivid green — as are those of typhoid, paratyphoid D. and B. enteritidis. RAXSOHOFF MFMORIAL J-()LUMH Antigens from all strains tested were prepared at one time and kept under the same conditions. Cultures were washed and suspended in 0.9% salt solution, killed at 65 C. for thirty minutes, freed of clumps and preserved with 0.5% phenol. -Agglutinating serum for B. influenzae and the Koch-Weeks bacillus were pre- pared by inoculating rabbits with living cultures. In the case of M 5 a dead anti.gen was necessary. The scrums had a rather low titer, about 1 :800. T.\P.I, ACCLUTIN ATIOS AND AbSORPTIHX REACTI INS Mother .Antiserum Koch Weeks Antiserum Designation of Strains Simple Homnlugous Simple HomoloKOus .XgRlutination Absorbed Agglutination Absorbed 1. MollKr 1 -f- 1 + 2. R -r 1 -f- -1- 1 P + P + I + 5. M (.. S + 1 -1- — + 1 P __ 8. \ __ 9. Sum 10. K — 1 11. Uo — 1 12. Koch Weeks -t- + As shown in Tal)lc 1, four of the strahis from the f;iniily S.. mother, 1!., S. and M., and strain C from a healthy individual, are probahly iden- tical. One other of the family strains, H., is somewhat related to this group, but is about as closely related to the Koch-Weeks bacillus. This agrees with the work of others in showing that there are distinct serologic groups among the influenza bacilli and that some strains are closely related to the Koch-Weeks bacillus. Blood serum from some of the recovered members of family S., who had harbored B. influenzae, contained no agglutinins for this organism. yXTTEMPTS TO TR.WSMIT IXFLUl'.XZA TO WHITE MICE A\D RATS, GUINEA PIGS AXn RAlUilTS V.Y .\1EA.\S OF SPRAYED SPUTUM Sputum, or, when this could not be obtained, material swabbed from the tonsillar area, but generally both, were thoroughly shaken with 0.9 per cent, salt solution and sprayed by means of a \'ilbiss atomizer within half an hour after collection. The animals were ])laced in a metal box about 12 X 10x6 inches, jirovided with a glass window and air outlets. The spray- ing was continued until the chamber was filled with vapor. This was re- peated at intervals tiiitil 15-20 c.c. had lieen sprayed, .\fter from 30-60 minutes the animals were removed from the cage and each series kept in separate cages. These were scalded with hot water before they were used for any given series. The sawdust bedding was not sterilized. Precautions were taken to sterilize the drinking pans in the case of all mouse experi- WILLIAM B. WHEKRY AND C. T. BUTTERFIELD ments. 'J'lic animals were fed on cracked maize and vegetalile waste from the hos]5ital kitchen. It might he noted here that one of ns in Cincinnati inoculated sterile milk with influenza sputum (1919) audi incuhatcd it at o7, 24 and IS de- grees for fr(jm 1-14 days, and fed it to white rats and white mice. Of ahout forty animals .so fed only two mice died, one with pneumococcus septicemia, and one with pneumonia and serous pleuritis due to four dif- ferent hacteria. None of these hacteria, singly or combined, produced in- fection when fed to other mice in milk or broth, cultures. Table 2 gi\es the data on these experiments. T.\HLE 2 Infi,uenz.\-Sputi'm Spraying KxpERiMtNT |g ■i 1 1, x;™ — II 11 ■s ^1 .2 i It "1 Us h c 5 - . Spray ^"S ,= « il E ill £-Z 5 2/ 3/20 Sputum S 5 mice 4 CI i9-;3 so .Ml like M5 killed) (MlfM2) 2/ 3/20 Sputum S Spray 4 white 2 2 (Wl.^VVJ) 13 50 Sterile 2/ 3/20 Sputum S Spray 2 guinea- 2 8-80 ion Uke !\I5 2/22/20 ^Torsi"- Intraperi toneal pigs 2 mice 2 (f,.-R-3) r.-8 100 General infec- tion like M5 2/23/20 Mi.\ed culture Ml plate Spray 2 mice 2 (M5.'M(.) 8-12 100 MG like M5 3/ 3/20 ^TnM"'- Spray 2 mice 1 12 50 Like MS 2/25/20 0.,anem... Orsan emul- Spray 2 mice 2/16/20 Intraperi- 2 while „ sion Wl. W2 toneal 4/23/20 ZTcT's Spray 2 mice ' 40 50 3/23/20 ZrcT% Spray 2 guinea- 1 " 30 50 General infec- tion like MS 2/ 4/20 Sputum cul- tures case S Spray 6 ''mice ' 2 31-45 33 No growth ob- tained from 2/ 4/20 Sputum cul. Spray 2 «»■-- " Killed fnd found nor- 2/ 4/20 Sputum cul- tures case S Spray 2 white » mal 5/2/20 2/ 4/20 Sputum cul- tures case S Spray 1 'rabhit 1 I (Rl) 8 ino G-l- coccu. present, lung large num- 2/ir,/20 Culture Rl Intravcn- 2 rabbits 2 34-40 100 "agent n.'l R^ intraperi- toneal 3/ 2/20 Sputum R and S Spray 2 mice 2 1 33-45 100 Like M5 2/ 2/20 iBj Spray 1 guinea PiR • 1 26 100 Like .M5 3/ 3/20 Spray 4 ' 30-38 511 Like M5. one sterile 4/ 4/20 Lung emulsion B and B 30- Intraperi- toneal 2 mice ' ' 50 Like M5 4/ 7/20 LungemuTsLn Inlraperi- 1 mouse ' 3 100 Like M5 3/ 5/20 Sputun,_ Spray 6 mice 1 52 Like M5 froul 3/ 5/20 SpuT'.m -r Spray 6 mice 2 72-84 __!'_ Like"M5 RAXSOHOI-F MEMORIAL VOLUME Family S.. Sputum Spray: Four of five mice died infected with a strain_of I!, cnteritidis" (type M5"): two of these died of a primary pneumonia due to MS. By the term primary pneumonia we mean pneumonia without marked involvement of the liver and spleen, which invariahly occurs in a general infection, i. r. after feeding. Of two guinea-pigs, one died of primary pneumonia due to M .t. One of two mice and one of two guinea-pigs sprayed with cxtrcats of the spleen. li\tr and lungs of this animal died of general infection with M 3. Two of four rats died of primary pneumonia and the long cultures yielded no growth, nor were subinoculations of organ extracts fatal to rats. Partial tension rabbit blood-agar plate cultures, from the sputum used for spray- ing the animals, were sprayed after twenty-four hours' growth at 37 degrees Of six mice, two guinea-pigs and one rabbit, only three animals died— two mice the 31st and 4Sth day were sterile bacteriologically, and one rabbit of primary pneumonia, ap- parently due to a gram-posiive coccus, which, however, did not appear in the two .subinoculated rabbits. R. and S. Sputum Sfray.—The two mice sprayed died of infection with M 5. one of primary pneumonia. The guinea-pig died of primary pneumonia due to M 5. B. and B.' Stutum of ^/?.— Of eight mice, four died, but only one of these had pneumonia due to M 5. Two had general infection due to M 5. B. and B. Sfitutn of 5/5.— Of six mice sprayed one died on the 52nd day of general infection with M 5. The rest, which were killed three months later, were found to be normal and did not harlior M 5. Sputum T. — Of six mice sprayed, two died on the 72nd and 84th days thereafter: one had a general infection with M S. The remaining four were killeil three months later and found to be normal. Siprayed with iutluenza .-putum coin])ri>e'l thirty-three white mice, of which four died of primary pneumonia and nine of a general infection with M 5. Of this same lot of mice, six were sprayed with culture material and of these two. which died, were sterile on bacterio- logic examination ; two were killed and cultured two months later and found to be uninfected, and two were used for another experiment in which they survied for a month. Of five guinea-pigs, two died of primary pneuinonia; the lungs of these animals contained numerous B. enteritidis, which were culturally and sero- logically identical (agglutination and absorption) with M 5. Of six white rats similarly exposed, two died of a primary pneumonia tlue to an unrecognized cau>e and not transmissible to rats by intraperi- loncal inoculation. The work of Krumwiede, Valentine and Kohn' shows that these animals may develop spontaneous infection with members of the paratyphoid-en- teritidis group. We did not encounter a single death among our unused stock due to such bacteria, nor were we able to isolate such bacteria from the intestinal tract, liver, spleen and lungs of six normal inice. However, the experiments detailed in Table 7 show that a certain number of mice which are intoxicated by killed cultures of M 5 or by the sterile Berkefeld filtrate of broth cultures, develop a secondary infection with M 5. In such endogenous infections, following intoxication, pneumonia occurred only twice in forty animals. Furthermore, of twenty-nine mice si)rayed with a virulent culture of the pneumococcus, only one died of infection with M 5. and this mouse had received a previous dose of M 5 toxin. On the other hand, as shown in ■Jour. MkI. Kcs., I'.'iy. Ml. \.. W. WILLIAM B. WHERRY AND C. T. BUTTERFIELD Table 5, mice exposed to sprayed cultures of M 5 almost invariably died of a primary pneumonia. In the light of these data one rs tempted tu believe that the animals developing infection with M 5 were injured in some way by something in the influenza sputum. Nevertheless, the possibility of purely spontaneous infection exists and the question can only be settled by further work with more adec^uate controls, /. c. an equal number of animals from each lot used for an experiment should have l)een kept under identical conditions as controls. IXOCUL.XTIOX OF OTHER .WIMALS From one of the typical cases, "R," 20 c.c. of blood was obtained. This was used to inoculate a series of animals not generally used m laboratory experiments with the hop" that a susceptible animal might be encountered. These were a pig, eight weeks old, weighing about 100 pounds, a ferret, an opossum, a salamander, and a black-headed nun. Wone showed any abnormal symptoms during three months' observation. The Cultur.m. .\xd .V.CLUTix.rrivE Rel.atioxship of M 5 (T.^bles 3 .\nd 4) Since all the enteritidis-like organisms isolated from the mice and guinea-pigs ex- posed to sputum sprays corresponded in their agglutination, absorption and cultural characteristics, we used M 5 alone for the comparative study. Unfortunately only two antiserums, M 5, with a titer of 1 :800, and paratyphoid B., with a titer of 1 ;10,00(), were available. Table 3 shows that M 5 is entirely distinct from paratyphoid B., but that it is indistinguishable by this te.st alone from Danysz virus and from B. enter- itidis. However, the cultural results (table 4) show that Danysz virus agrees with paratyphoid B. in its failure to ferment xylose, while M .i agrees with B. enteritidis i;i the fermentation of this substance. This divergence was brought out by Krumvveicle et al.' We have been helped also in this study by reference to the work of Jordan,' and preceding articles cited here and that of Winslow, Kligler and Rothberg.* The Danysz virus and paratvphoid B. were from the U. S. Hygienic Laboratory and th- B. enteritidis was of the' Gaertner type and came from Prof. E. O. Jordan in 1901. Five cultures of B. enteritidis-like organisms isolated from the stools of influenza patients by Sherwood, Downs and McXaught,' were sent by Dr. Sherwood. None of these agglutinated with M 5 antiserum. F.xpEKiMENTs Showing Th.vt Broth Clltlkus oi WITH which .\x .Axtitoxix M.' .\I5 Cnxr.MX • Be PRonucED Plain maltose and dextrose beef infusion broths were tried. It was found that 01% dextrose broth ( +0.05) yielded the most potent toxin, .\fter incubation at 37 C. for 4-5 days the culture was filtered through a Berkefeld N. The filtrate would kill mice in 12-18 hours when 0.05-0.1 c.c. was injected intraperitoneally. Seventy mice were used in establishing the nature and potency of this toxin. Mice dying of intoxica- tion showed marked injection of the sulicutis and congestion of the lungs. Often the of Strains Para B. Antiserum MS Antiserum nesig.iation Simple Agglutination Homoloious AbsorteT Simple Agglutination Homologous * Absorbed' M-5 '. 1 .L Par.i B 1 •i- -f- I 1 l Med. Res., 1919, 39, p. AA9. Infect. Dis., 1920, 26, p. 427. BactL-riol., 1919, 4, p. 429. Infect. Pis., 1920, 26, p. 16. RAXSOHUFf MEMORIAL VOLUME pulmonarj- congestion bordered on consolidation. The In capillary hemorrhages. Other organs and tissues appcan We found that about 2 c.c. was the M L D, on in rabbit weighing 1.800 gm. By inoculation with sublethal ing the amount at two-day intervals, over a period of gs often showed normal to the eye. avenous inoculation, for a and gradually increas- eeks. a rabbit could .I..S. tolerate 5 c.c. of a freshly prepared toxin. Eiglit days after the last dose of toxin the serum of this rabbit would protect mice when mixed with 2 M L D of the toxin and at once inoculated intraperitoneally. In the experiments summarized in Table 7 the vaccine was prepared by suspending an agar culture in 0.9% salt solution, heating at 65 C. for si.xty minutes and preserving with 0.5% carbolic acid. The density was somewhat greater than that of a 24-honr broth culture of B. typhosus. The dosage was approximately two minims for each inoculation. Several tests of the vaccine before and after its use showed that the bacilli were dead. TABLK 4 The MuuPiioLOGic .^.^■n CrLiLR.^i. Ch.^r.«teristics cr M .=; anp of KtPKtsENT.M ive 0»c.\nism» Selected from the S.^me Group Ml JJjjll) l + l + i + l— 1 + .— I— I— I + lag'laglagl — lag:— laglaglagl— aglagl— I— lag l + l + l + l — ! + l — I — I— I - lag jaglagl — lagl — laglaglagj— aglagl— I— I— 1 + 1 + 1 + 1 — 1 + 1— I — I— + lag aglag— jag!— jaglaglagl— aglagl— I— I— l + l + l + l— l + l — I— I— I + lag laglagj — lagl— laglaglagl— aglag;— 1— lag XPERIMENTS Showing th.^t when Ai Percentage Develop Pnei'Moni.\, a Virus; while a Spray of I AN INFLI'I TABLE s ARE Exposed THE Spray of M 5 Cultures a Large ILAR Results Follow the Spray op Danysz ■48 Hours Previously from jt effect Percentage Dale Aniina Is Number of Dead Ani- mals with Prima ^; ration of ness in Days Pvcmarks [ Pneumonia 3/12/20 4 mi 1 4 1 I 100 4-20 1 1 3/17/20 10 mi e 1 8 1 100 4-15 3/30/20 ^ 1 4 1 75 1-10 1 Sublethal . ..i antcn..r an. I n..-!'. n..r I..1.,/. I'n. ACTU.-\I.I Inh.m.ed Into the .1 u li a broth culture of M 5, and ning of the experiment. They rill of mercury for five minutes, nd from each animal 4-6 small ped off with sterile scissors and ed o-i-owth of M.s within twentv- 'le rxlrenie .listal |i.,rtions of the ii'.K wire ireate.l m the same RAXSOHOFF MEMORIAL VOLUME Attempts to Produce Pneumonia in ^ficE by Spraying Pneumococci Having shown that sprayed bacteria reach the deepest alveoli, or capillary bronchi, of the lungs and that pneumococci planted in this way survive in the lungs of mice for at least eighteen hours, the maximum period tested, we made the following experi- ments with a type 1 pneumococcus. This culture had been kept highly virulent for mice at the United States Hygienic Laboratory. Four mice were sprayed with the growth from four blood agar slants suspended in broth. They were exposed for thirty minutes. Two died of primary lobar pneu- monia in fourteen days. No bacteria could be found in the purulent exudate and all cultures remained sterile. The remaining two were killed six weeks later. They appeared normal and cultures from the lungs remained sterile. The mice were kept at 8 C. for four hours and then sprayed. They felt warm on removal from the icebox. Two were killed and cultured shortly after spraying. Pneumococci grew out of all pieces of their lungs, including the most distal portions. At the cml of four weeks the remaining eight mice were chloroformed and cultured with i)^■^.l[l\r rr~\\]\<. Siiic^' M 5 ^ 'liiMc toxin injures the lungs of mice, six mice which bad survived sublctlial (Insts (if this toxin given ten days before were sprayed. They were killed si.x weeks later and fmnid normal. Xor did they harlmr pneumococci. Four mice were given Mililethal doses of M5 toxin ami sprayed with pneumococci at once. Six weeks later one of these mice died of pneumonia caused by M5: no pneumococci could be found. The remaining three were killed and cultured eight weeks lalcr. Thc\ were normal and the cultures remained sterile. Three mice were sprayed with the pneumococcus and then in an attempt to give them an acidosis they were kept under ether for one hour. One of these was further chilled in ice water for ten minutes. They survived and yielded no growths four weeks later. Two mice were sprayed with a broth suspension of bloody sputum from a case of pneumococcus loliar pneumonia. They remained well during six weeks' observation. Since none of tlie t\vent_v-nine mice became infected after inhaling viru- lent pnetmiococci into their lungs, one ma}- conclude that some predisposing factor must precede or accompany such an implantation of bacteria. While we owe the whole idea of droplet infection to Fliigge and his pupils and confess that we have relied on the review of their work by Goetschlich," we are not aware of the fact if these workers demonstrated that bacteria are to be recovered from the deepest portions of the lungs of sprayed animals. Our attention was drawn to this by Rogers," who showed that tubercle bacilli could be recovered from the lungs of guinea-pigs immedi- ately after spraying them with tuberculous sputum, and that such protected and sprayed animals develop true primary pulmonary tuberculosis. We are familiar with the work of Diirck,^ who, by means of intra- tracheal insufflation, was unable to infect the lungs of rabbits with freshly isolated cultures of pneumococcus, streptococcus pyogenes, and staphylo- coccus ain-eus unless at the same time, or before or after, injurious dust particles, pumice, or "Thomasphosphatmehl" were also blown into the lungs. This sterile dust alone produced pneumonia while sterile street dust did not. He also describes the production of typical pneumonia in rabbits, with secondary invasion of the pneumonic areas by B. coli, sarcinae,, or Fried- lander's bacillus, by keeping them at 37-41 C. for sixteen to thirty-six hours and then in ice water for two to seven minutes. « H.in». and 1920. 1. p. 7.S0. ' Dcut, .\rch. f. kliii. Med,. 1897. 58, \,. 308. WILLIAM B. WHERRY AND C. T. BUTTERFIELD However, these experiments and those made by the method of intra- bronchial insufflation, which was introduced by Lamar and Meltzer and used by many others, do not appeal to us as represnting what must take place under natural conditions. Bacteria can be inhaled into the deepest parts of the lungs and if they are capable of multiplying there they will produce pneumonia, as in the case of M 5. The fact that virulent pneu- mococci do not multi]:)ly when planted in the lungs of mice by air currents is an interesting fact and deserves further investigation. SUMMARY .\XD CONCLUSIONS When white mice, white rats and guinea-pigs were exposed to finely divided influenza s])utum sprays some died of a primary pneumonia, others of a general infection due to a .strain of B. enteritidis (type M 5). Since the work of others has shown that these animals may die of spontaneous infection with members of the paratyphoid-enteritidis group we can not say that these infections were necessarily the sequel to the spray. How- ever, as primary pneumonia could not be produced in mice when M 5 was inoculated through the buccal or gastro-intestinal mucosa, the conjunctiva, subcutis or peritoneal cavity, but only when sprayed, it seems to us likely that something in the sputum sprays produced a change in the pulmonary tissues favoring such secondary localization. Broth cultures of M 5 contain a soluble toxin which produces marked congestion of the subcutaneous and pulmonary tissues of white mice. This toxin gives rise to an antitoxin when injected into rabbits. Previous inocu- lation with the toxin did not produce immunity to the development of pri- mary pneumonia by sprayed cultures, nor were we able to immunize against the spray of M 5 cultures by previous subcutaneous inoculations with a dead culture. The intoxication of mice with the soluble toxin or with killed cultures of M 5 apparently led to infection with M 5 in a small percentage of the used mice. We were not able to find this bacterium in normal mice, nor did spraying mice with virulent pneumococci make it show itself as a secondary invader. Experiments show that AI 5 and virulent pneumococci are inhaled by mice into the deepe.st alveoli or capillary bronchi of the lungs, and that pri- mary pneumonia follows in the case of M 5, which is capable of growing and producing its toxins there, whereas the virulent pneumococci gradually disappear. THE PRIXCIPLES OF TREATMENT IX MERCTRIC CHLORID POISONING WITH RESULTS OF TREATMENT* H. B. Weiss. M.D., Cincinnati. Within the past two years there has been much work done in the vari- ous phases of mercuric chlorid poisoning. Before then, most of the work reported was of a therapeutic nature ; but recently new and important laboratory data have been contributed. These new data have certainly put the modern therapeutic measures to the test, discrediting many and placing a few on a firm basis. The anatomic pathologj' has been well established. E\cry organ of the body is affected, the liver and kidneys bearing the brunt of the injuries. From a cloudy swelling the changes continue to fatty degeneration and necrosis. When the poisoning is severe, hemorrhagic inflammation may supervene. Schamberg, Kolner and Raiziss,^ in their studies of the comparative toxicity of the various preparations of mercury used for therapeutic pur- poses, have shown in a long series of dogs that every animal develops evi- dences of nephritis of varying degrees after injections of both the soluble and insoluble mercury salts. The nephritis produced is primarily tubular, with frequent accompanying glomerulonephritis (hemorrhagic) in the se- verer instances. The changes in the tubular epithelium they attribute to a direct toxic degeneration of the cells by the mercury, and not to an inflam- matory reaction depending on the elimination of toxic substances. Mercury has been obtained from the blood of dogs within ten minutes after its administration by mouth.- Burmeister and McNally have shown that the kidney changes vary with the size of the dose in massive intoxica- tion, and that the liver changes depend on the duration of the intoxication. The im])ortant newer studies consider the fpiestion from a chemical standpoint. It is from tliis point of view that the present treatment must be evolved. .■\s tlic mercury is cjuickly taken up by the blood after ingestion, it is evident that all the tissues are quickly bathed with the toxic material. In a fatal case of mercury poisoning, it was found that almost one-third of the mercury recoverable from the body was obtained from the blood. ^ In 1916, • From the Department of Medicine, University of Cincinnati College of Medicine, and the Medical Clinic, Cincinnati General Hospital. — From the Journal of the .American Medical Associa- tion, September, 1918. "Schamberg, J. F.. Kolmer, J. A., and Raiziss, G. M.: A Study of the Comparative Toxicity of the Various Preparations of Mercury, Jour. Cutan. Dis., 1915, 33, 819-8J0. •Burmeister, VV. H., and .McNally, W. 1).: Mercury Poisoning, Jour. Med. Research. 1917. 3(<. 87. the liody in a Case of Acute H. B. WEISS Lewis and Rivers* found that the retention of waste nitrogen was a factor in the production of early fatalities. More recently MacNider/ in an ex- haustive study, has demonstrated some essential facts. Those animals that did not succumb from the early gastro-enteritis developed a severe type of acid intoxication, as evidenced by the production of acetone bodies, the re- duction of the alkali reserve of the blood, and the increase in carbon dioxid content. Constantly associated with this acid intoxication was a kidney in- jury. He states that delayed kidney injury is not due to the action of the mercury as such during its elimination by this organ. He" had previously shown that acetcjiie and diacetic acid are developed in nephritis produced by uranium, and that administration of alkaline carbonates lessened the PI -^--''^^^"^----^ bU : ..-^'^ 4a . / ■■^ : : : M .-,--■-: '' \ : '/ : ^ 18 y -■- i hi Sit !-^- M i H ; ■ : ■ . :h-H--l!-H--K--H-i-H ; ■ ' ::/ - J ■--^■:i-^-;•:MM^•^;-:■v:-:-Hl ^ DwT 5 10 D 20 25 30 35 40 toxicity of the tu-anium and delayed the formation of the acid bodies. Furthermore, when the kidney was protected by carbonate, it was found that the kidney remained functionally more active, and that there was a diminished acute swelling, fatty degeneration and necrosis of the renal epithelium. It is this work which has proved correct the therapeutic principles that I have em])loyed in the treatment of mercuric chlorid poisoning.' The symptoms of poisoning by mercury are well known : locally burns, and later vomiting and gastro-intestinal hemorrhages ; as the toxemia prog- resses, oliguria, then anuria and finally "uremic" .symptoms, as convulsions and death. Many remedies, empiric and allegedly scientific, have been advocated in the use of mercury poisoning, but they seem not to have stood the test 1 a Case of Bictiloride Poisoning, Johns Clilorid Intoxication in tlie Dog with ' .M-icXuicr, V\. ,1c K.; Tlic liil bonate. and the Protection of the Kidn of an Anesthetic by Sodium Carhonal 'Weiss, H, B.: .\ Method of Tr< June 2, 1917, p. 1618; The Tr 1917 13, 597. RAXSOHOFF MFMORIAL VOLUMF of time, ^^'e have used tlie alkaline treatment for more than three years, and our records show a lower mortality than that ordinarily reported. The principle involved in the use of alkali is that of trying to counteract the acid intoxication produced, which in turn produces the generalized toxemic swelling and degeneration of all the body tissues.^ When there is present oliguria, with blood and casts in the urine, we have evidences of acute kidney injury. This discernible kidney injury is merely an indication of an injury common to all the body tissues, for we know that the entire organism has been bathed by the mercury. The alkali is not given as an eliminant, but to counteract acid intoxication, edema and cloudy swelling, which, if permited to go on, proced to fatty degeneration and irreversible cell damage (necrosis). Sansum," in a recent paper, seems to believe that the basis for the use of alkali is to be found in its power to increase diuresis with a secondary washing out (increased elimination) of mercury. Because he finds no in- creased mercury elimination, he leads his readers to suppose that the use of alkali as a therapeutic agent is valueless. The alkali, however, is not used solely for its eliminatory action, but to inhibit and to counteract damage to the tissues which mercury, if left to itself, produces. At present we can report on fifty-four consecutive cases of mercurial poisoning with but three deaths. Of the three patients that died, two re- ceived the treatment only after unavoidable delay, and one had a pre- existing ne])hritis and cirrhosis. METHOD OF TKF.ATMEXT Essentially the treatment which I have jiroposed consists of an early washing out of the mercury salt from the stomach and intestine and con- tinued introduction of sufficient alkali to overcome the acid intoxication. The patient should come under observation as early as possible, for I have found that when the treatment is delayed for any reason, the symp- toms produced by the mercury poisoning become more difficult to control. Two patients of my series died, I think, because treatment was commenced too late. I usually wash out the stomach with a mixture of one quart of milk and the whites of three eggs, following this by a saturated solution of so- dium bicarbonate until the stomach washings return clear. Finally, before the stomach tube is removed, from three to four ounces of crystallized magnesium sulphate dissolved in from six to eight ounces of water are allowed to remain in the stomach. A .soap suds enema is then given. Usually the i)atient vomits shortly after taking the mercury, thereby aiding in the elimination of the poison. The next step is to introduce alkali, and we give the alkali by mouth, rectum and intravenously. As soon as possible after washing the stomach, • Fischer, M. H.: Edema and Nephritis, New York, John Wiley & Sons. 1915. •Sansiim. W. D. : The Principles of Treatment in .Mercuric Chlorid I'oisoning. The luiirnal .\. M. .\., March 23, 1918, p. 824. H. B. WEISS the patient is given Fischer's solution intravenously. Fischer's solution consists of crystallized sodium carbonate, 10 gm. ( NaXO,,10H;O) (or 4.2 gm. of the ordinary "dry" salt) ; sodium chlorid. 15 gm., and distilled water. 1.000 c.c. Depending on the state of the circulatory system, from 1,000 to 2.000 c.c. of the solution are given intravenously as a first dose. We continue the alkaline medication by giving eight ounces of "imperial drink" every two hours. This drink consists of: potassium bitartrate (cream of tartar), 4 gm. (one teaspoonful) ; sodium citrate, 2 gm. (one-half teaspoonful) ; sugar, 2 gm. (one-half teaspoonful), and water, 240 c.c. (eight ounces). This drink is flavored with lemon or orange juice. The patient is allowed large quantities of it. There is no restriction in diet at any time during the treatment. As an indication of the severity of the acid intoxication, and as a guide to the amount of alkali and salt that needs to be given, we use the analysis of the urine. Except in suppression cases (which were rare in our series), the patient voids large quantities of urine, the amounts depending on the amount of fluid taken. The urine should become alkaline to methyl red (a saturated solution of methyl red in alcohol) and be kept so, for Fischer has demonstrated that if the urine of a nejjhritic can not be maintained alkaline to methyl red, the patient continues in a serious state. If the out- put of urine is not seen to be maintained, and if its reaction does not be- come alkaline to methyl red after the first intravenous injection, a second intravenous injection is given the following day, and general alkali admin- istration by mouth or rectum is continued. RESULTS Under this treatment, there is usually produced and maintained a free secretion of urine which remains alkaline, and an output of albumin in the urine, which usually develops early, rapidly disappears. Ordinarily two intravenous injections of the alkali, together with the solution of potassium bitartrate and sodium citrate, which is given at hourly or two hourly in- tervals, day and night (when the patient is not asleep) has been found sufficient to keep the urine alkaline and to keep the output of urine normal. The blood and casts in the urine are usually quickly dissipated. Tiie pa- tient is kept under observation for about ten days after the urine has be- come normal, and is then discharged. • I have shown previously" that patients treated early show fewer symp- toms and make a more rapid recovery than those in whom treatment is delayed. Page 567 RAXSOHOI'l- MllMORlAL VOLUME We have performed phenolsulphonephthalein tests on most of our pa- tients, and it is interesting to note that those who were treated early showed only slight or no diminution in phenolsulphonephthalein output. When the output was diminished, it rapidly rose to normal and continued so. In one patient who developed an anuria for three days,^" the phenol- sulphonephthalein output was practically zero for five days after he com- menced to void, and then rapidly rose to 66 per cent, (as shown in the ac- companying chart) at the end of thirty-three days. This patient's urine was normal six months after his recovery from the mercuric chlorid poison- ing. THE \'ENEREAL PROBLEM. PiTiLip Zkxnf.r, A.m., M.D.. Cincinnati. My subject is the venereal prolilein ; that is. the problem of the prevention of the venereal disease. This is no new problem. Many years ago, a great American surgeon e.xpressed the fear that these diseases would lead to the deterioration of the whole human race. Have these diseases been on the increase as this fear suggests? \\'e have no data which enal>le us to give a definite answer to this question, but there is much which gi\es that appearance. When I was a student, jiaresis and locomotor ataxia (I suppose that you know that they are due to syphilis) were rarely found. Today we see I hem frequently. But we know much more about these diseases than we did in those days, and, therefore, more readily recognize them, and this may be the full explanation of their apparent greater frequency. Then we have a new test of syphilis, a blood test — the Wassermann test — which enables us to find the disease in many cases where it would otherwise have gone unrecognized. We have also a new test for gonor- rhea, so that now we know that gonorrhea is common in women and chil- dren, of which fact we were not formerly aware. In women the disease often leads to confirmed invalidism and is a common cause of sterility ; in children it often causes blindness. These facts do not prove that venereal diseases are on the increase, but they have aroused the world to a knowledge of their prevalence and their danger. The problem became acute when we entered the war. War always has increased the venereal diseases. They spread rapidly in armies and after the war the soldiers spread them among the people. That was the experience of this war. In some of the European armies these diseases disabled more soldiers than did shot and shell. Their effect was equivalent to the wiping out of whole army corps, and since the war the disease has played havoc with some of the European peoples. The knowledge of such facts led our government, when we entered the war, to take rigid measures to prevent the spread of the venereal diseases in our army. These measures were phenomenally successful. Let us briefly review them : First, the soldier was kept bu.sy and thereby out of mischief; during his work hours, busy with his training; during his hours of leisure he was given wholesome entertainment. Secondly, he was forbidden alcoholic drinks and houses of prostitution were banished from his neighborhood. Thirdly, he was given sex instruction by means of pamphlets, moving pictures, talks from his ofificers and special lectures. He learned that con- tinence is altogether consonant with health and vigor, whereas he had pre- viously been taught that sexual indulgence was a necessity. He learned RANSOHOFF MFMORIAL VOLUME that not only \\as syphilis a disease he already dreaded, a grave disease, but that gonorrhea, a disease he had been accustomed to look upon lightly, was also grave, sometimes worse than syphilis. This is especially true because of its complications. For instance, 10 per cent, of the cases of gonor- rhear in our army had gonorrheal rheumatism, the worst form of rheuma- tism. He learned also that a man may believe himself to be well while the disease is still lurking in his system and mav later infect his wife and children. 'I'his sex instruction had a decided influence ujion the soldier's conduct. Finally there is the measure we term ]mjphylaxis, preventixe treatment in case the individual exposes himself to infection. This consisted usually of urethral injection of a 2 per cent, silver solution and an external appli- cation of a mercurial salve. The order was imperative that the soldier have this treatment in case of exposure. To see that the order was enforced the soldier was examined at least twice a month, and if disease were found and he had not previously apjilied for treatment he was court-martialled and severely punished. As I said, these measures were phenomenally successful. As Surgeon- General Blue expressed it, "The venereal rate was lowered below that of any army of any nation in the history of the modern world." But even then the venereal disease in our army was by no means an insignificant matter. It was still the most disabling single factor, in truth more disabling than all other acute diseases together, leaving out influenza and measles. Some figures will give you an idea of this. One week when I had occasion to look up the records of Camp Sherman, there were 1,700 patients in the hospital, and of this number 800 were cases of venereal disease. Between September, 1917, and September, 1918, there were 170,000 cases of venereal disease in our army. But I would not have these figures mislead you as to the efliciency of the campaign against these diseases. Only in the smaller number, about one-sixth of these cases, was the disease contracted after the soldiers entered the army. In the larger number, about five-sixths, the disease was contracted before they entered the service ; it was acquired in civil life. 'J'his brings us to the problem we have before us today — what can be done to prevent the disease in civil life. Let us again consider a few of the measures so efYective in the army, and first the suppression of houses of prostitution. This measure was very effective in the army. To illustrate this fact I will mention the e-xjierience of an army corps in the French corps in the French |3ort, v^aint Xezaire. where ])rostitution flourished. Before the division reached this port its disease had been reduced to the low annual rate of fifty-four per thousand. In Saint Nazaire the rate soon rose to two hundred and one. When this was observed, the houses of prostitution were put bcvond the soldiers' reach and the rate fell markedly at once. Page FHILIP ZENNER We could not expect an equal effect in civil life where there is neither the same discipline nor the same control, but still, good must come, if only from the physical possibilities. A woman in a house of prostitution some- times has contact with fifty men or more in twenty-four hours, whereas if she must seek her prey on the street she can not find nearly as many victims. And now as to prophylaxis. That had a great eft'ect in the army. Some figures again will make this clear to you. In one division, where the matter was carefully studied, it was found that of those who had received prophy- laxis only one in ninety contracted the disease, whereas one in thirty be- came infected where this treatment was not applied — a reduction of 662;:j per cent. Nevertheless, it is very unlikely that this measure will lessen the prevalence of the disease in the community, and this for two — people will not apply for it, and the time they would apply. Army experience throws light upon this statement. In our own army, notwithstanding the severe punishment inflicted if the soldier did not apply for the treatment after exposure, from one-fourth to one-third of the men failed to do so. The report of a British surgeon is still more illuminating. According to his report, the treatment was a voluntary matter with the soldiers, but they were offered every facility for its application, and yet not one among some thousands of men made use of it. In civil life, where secrecy is usually desired, there would be still less likelihood of the in- dividual seeking the treatment. As to time, the usual experience has been that when the treatment is applied immediately, or within an hour, after intercourse, it is almost in- variably successful, but that after a number of hours has elapsed it is use- less. This brings up the question of self-treatment, the individual being supplied with the necessary remedies and applying them himself immedi- ately after intercourse. If this procedure were a common one there is no doubt that it would increase rather than diminish the amount of ve- nereal disease, for usually it would be applied imperfectly and be no source of protection while the sense of security given would lead many into danger which they would otherwise have shunned. There is extended experience in demonstration of the truth of this statement. Before the war this mode of treatment was in vogue in our navy and it was also tried in the New Zealand expeditionary force in France. In both instances it proved to be a failure. I have spoken so fully of i>rophylaxis liecause there are those who be- lieve that it is the means of the control, if not the eradication, of these diseases, whereas unless the facts I have given you are altogether mislead- ing, we can expect little or nothing in this way. Our government did not discontinue its campaign against the venereal diseases when it discharged its soldiers. Each year since the war Congress has appropriated $2,000,000 for this purpose. This money is divided among Page 57/ RAXSOHOFf MEMORIAL VOLUME the states, which will provide an amount equal to that given them, and now in forty-seven states this campaign is carried on. the national, state and local health authorities working together. So far their effort has been de- voted chiefly to finding and curing existing cases of disease. \'enereal dis- ease is very contagious. It is catching from person to person. If every case could be cured there would be no further source of contagion and the disease would vanish from the earth. This is a practical impossibility, but lo the extent that cases are cured is the prevalence of the disease lessened or at least its increase diminished. One of the greatest obstacles to finding and curing cases of the disease is the quack and quack nostrums. The only object of the quack is to make money, and to do so he deceives the people. His treatment is likely to be inadequate and he is likely to lead his patient to believe that he is well, while the disease still lurks in his system with all its possibilities of harm. Durng the war. when man power was of vital importance, England severely punished quacks who treated venereal diseases. One of our states, Ala- bama, recently enacted a law forbidding the advertising of quack venereal doctors and the advertisement and sale of quack venereal remedies. Many of the best newspapers in the land w-ill not accept any medical advertise- ments. But to really escape the danger of the quack, the people must have a full understanding of the matter. They must know that the quack is a source of harm, whatever disease he pretends to cure, and though he be graduated physician, that he deceives the people, that he plays upon their their fears and often falsely arou.ses fear, that every advertising medical man is a quack and most advertised medicines quack nostums. One of the great purpo.ses of this national campaign is to tell about the quack. Another measure is the establishment of free clinics for the treat- ment of those unable to pay. Here they are given the most modern methods of treatment and are urged to continue the treatment until they are quite well. Also lectures are given to the people in factories and many other places. The lectures aim to tell about the venereal diseases, their danger, their contagiousness, and the great need of avoiding them. They also urge the diseased to go only to competent men for treatment and to remain under treatment until cured and no longer a danger to others. Many laws have been enacted to help along this campaign. Most states require that physicians report all their cases of venereal disease. This is essential if the campaign is to be successful, for there can scarcely be a sucessful fight against a disease without some idea of its degree of prevalance. Many states require physicians to hand their patients printed instructions how to avoid giving the disease to others, and if these instruc- tions are not heeded health authorities have the power to quarantine the patient. Many states have made so-called eugenic laws, laws to control marriage, to forbid the marriage of infected individuals. There is a great difference between making laws and enforcing them. Certainly it is a difficult matter to get physicians to report their cases, Paijc .r.z PHILIP ZENNER almost the foundation-stone of this whole structure, ^^'e cannot tell of the future, but we can say that the full success of this campaign will de- pend upon national, state and local health officials, as well as physicians and voluntary associations established for the purpose, working together and upon an informed and sympathetic public sentiment. The question arises whether this campaign, now going on nearly two years, has lessened the cases of venereal disease. Probably not. There is much that militates against it, especially the prevailing tone of society. We are feeling something of that moral laxity which always follows war. Some weeks ago we were informed that our dances are 30 per cent, more im- moral than they were one year ago, and 150 per cent, more immoral than ten years ago, and there is much more which points the same way. Never- theless, we can not question that this campaign has done good, if not in lessening the actual number of cases, in preventing such an increase as might otherwise have taken place. When society has assumed its normal tone, if the campaign is conducted on the lines I have just indicated, it will achieve great results. But even then one must not expect too much ; even then there would still be a la- mentable amount of venereal disease. To bring this anywhere near the vanishing point something more radical is necessary. This something is education. It is true much has already been done by means of lectures, already mentioned, and the results have been good. But the education I have in mind is more than that. It is the education that can be given to all and at a time of life when harm has not yet been done and when it can influence the whole life. I am alluding, of course, to the sex education of the young. This means essentially education in the home. All the testimony we have points to the value of this teaching. Ques- tionnaires here and there have brought out that the results are always good. But there is comparatively little such teaching. An inquiry among thou- sands of college men revealed that only 4 per cent of them had been taught at home, and Dr. Richards, a high school teacher of girls in Philadelphia, stated that only from i/^ to 2 per cent, of her girls had received any sex instruction in their own homes. You know the usual mode of sex instruction: The child gets it on the street and gets bad and perverted ideas. On account of the way it is taught and because its questions receive the harsh word at home, it is led to look upon these matters as shameful, and so is separated from its parents. In a way, it leads a secret life. When the boy gets older he is taught by the gang that sexual indulgence is necessary for health. This and like in- fluences lead him to an illicit sexual life. The teaching should be just the opposite to this. It should be in the home. The parents should be the teachers; of the growing child, the mother. The teaching should be according to the child's age and needs, beginning when its curiosity is aroused and it asks questions. It should be done in such a Page ilS RAXSOHOFF MEMORIAL VOLUME manner as to arouse a reverent spirit in the child. It should he led not to discuss the matter with others, hut to always come to the mother when it wants information of this kind and to make of her an utter confidant. Taught in this way instead of looking upon these things as shameful, it sees the heauty and sanctity of life. It acquires knowledge which safe- guards it from many pitfalls. It gets high ideals. Above all, it gets an utter confidant in the mother, often its means of salvation. One can not rate too highly the value to the child of this utter confidant. She is often enabled to safeguard it from impulses in its own heart and from countless corrupting influences about it. It is not so rare that a single child has corrupted a whole group of children or almost a whole school, where a mother, having the confidence of her child, could have prevented the trouble or at least stemmed the tide of corruption. The mother should teach the young child, but. when the boy is older, the father should play his part. It is because so few parents teach their children that there is demand for sex instruction in the school. This is part of the program of the na- tional campaign against the venereal diseases and really its most important part. But as yet nothing has been done except the beginning of prepara- tion of teachers. Teachers should be thoroughly competent. There is no doubt that unprepared and incompetent teachers can do much harm. The teaching should begin with the young child. The consensus of opinion is that the child should be led gradually from the knowledge of reproduction in plant and animal to human reproduction and that the teaching should be a part of a general course, such as physiology, biology, domestic science or physical education, so that this knowledge will come to the child almost imperceptibly. School instructions might be of infinite value, for thrreh\ all children could get the right sex education. Children could get not only knowledge to safeguard them and ideals to elevate them, but also better companions, companions who have also had sex instruction, as well as find less corrupt- ing influences in society, for with universal sex instruction the tone of so- ciety would be elevated. Not the least, perhaps the greatest, benefit of school instructions would be that it would prepare a new generation of parents who would give their own children sex instruction. Just a word more. There are often violent outbreaks of disease, even widespread, where the jjecple can throw all the responsibility upon the health authorities with the assurance, ])rovided due support be given them, that the diseases will be stamiicd uul. Xot so the venereal diseases. Health authorities alone can nt)t stamp them out or come anywhere near doing so. The whole responsibility can not be thrust upon them. Tiiese are the most widespread, the most menacing ol' all di>ea'-(s. They are a world ]M-oblem and a jiersonal problem. < »iight not cxeryone. ought not each of us, feel and assume his >li:irc ut' that rc>pun>iliility. a rcsi)onsibility met Iiy trying to understand the problem and its solution. !)y his conduct and bv his influence? UNIVERSITY OF CALIFORNIA LIBRARY Los Angdes This book U DUE on the last date stamped below.