THE LIBRARY OF THE UNIVERSITY OF CALIFORNIA LOS ANGELES GIFT Emil Bogen, M.D. TUBERCULIN AND VACCINE IN TUBERCULAR AFFECTIONS A Practical Guide for the Utilization of the Immune Response in General Practice BY ELLIS (BONIME, M. D. Adjunct Professor of Surgery and Division of Immunotherapy, New York Polyclinic "Medical School and Hospital THE SOUTHWORTH COMPANY, PUBLISHERS TROY, NEW YORK 1917 COPYRIGHT, 1917 BY THE SOUTHWORTH COMPANY WF To the memory of my MOTHER, whose sacrifices have shaped my career, and to Prof. JOHN ALLEN WYETH, M.D., LL.D., who has given me the opportunities that made my experiences possible, this work is gratefully dedicated by the Author. FOREWORD By JOHN ALLEN WYETH, M. D., LL. D. Having demonstrated to my complete satisfaction that the persistent and carefully adjusted injection of tuberculin will cause to disappear lymphatic glands enlarged with the inflammatory products of bacilli of tuberculosis, I undertook to establish a clinic in connection with my department of general surgery at the New York Polyclinic Medical School and Hospital, at which these cases could be treated. Dr. Ellis Bonime was placed in full charge of this clinic. His careful technique and conscientious study of each of these numerous subjects who presented themselves for treatment gave a final confirmation to the results of our preliminary work. As will be shown in the text of this volume, the beneficial effects of Koch's tuberculin are now also demon- strated in bone and skin tuberculosis, and the earliest stages of pulmonic involvement. To this department has been added the treatment of various infections by the use of vaccines and sera, a branch of surgical therapeutics as yet not as insistently taught or as widely practiced as our experience would seem to justify. JOHN A. WYETH. PKEFACE. There is, perhaps, no therapeutic agent which has so checkered a history as tuberculin. Every medical man is acquainted with the story of its rise and of its sudden fall ; of the prejudices and vicissitudes that have beset its career. However, we believe that the days for defending and apolo- gizing are past, and that every physician who has given the subject any serious thought is convinced that in tuber- culin we have the medium through which tuberculosis is destined to be conquered. However, to get any adequate control of this plague, we require a method for the use of tuberculin which will enable the general practitioner to handle it safely. Once the general practitioner is able to cope successfully with tuberculosis by means of tuberculin, the public will gain faith in tuberculin. We have come to realize that the education of the public is quite as important as proper treatment. The idea that the climatic treatment of tuberculosis is the only one known, and thus means ban- ishment from home and occupation, has occasioned a dread of the disease which has created a fear of diagnosis rather than a rush for early treatment. There is no better way of educating the public to come for early treatment than to have a method of treatment in the hands of the general prac- titioner which will make him able and willing to take the responsibility for treatment instead of shifting it by sending his patients away. The need of such a method struck me in the course of my work in surgery. I soon noticed, as most surgeons do, the futility of surgery in tubercular conditions. As I had a large and successful experience in the use of the immune response in vaccine therapy in all forms of surgical infec- tions, I could not help thinking that there must be some way of utilizing the immune response in tubercular conditions, especially where surgery so often proves hopeless, and where VI 11 PfiEFACE other forms of treatment would be so welcome. Thus it was, that when Dr. John D. Murphy of Chicago made his announcement that over a period of two years he had been able to avoid operations on cervical adenitis by the use of tuberculin, I began to use tuberculin in this condition, with pronounced success. As my experience with the use of tuberculin grew, I became more and more convinced as to the fficacy of the artificially induced immune response in tubercular conditions. As I went further into the literature on the subject, and observed the physiological action of tuberculin, I came to realize that the immuno-mechanism in tuberculosis was exactly the same as in any other infec- tion, except that the hypersusceptibility and the production of substances during the immune response was responsible for the dangerous element in the improper use of tuberculin. I observed that the hesitation on the part of the profession to use tuberculin was due to the necessity of judging the patient's degree of hypersusceptibility. Working along these lines, I finally evolved a system of dosage which eliminates the necessity for judging the hyper- susceptibility of the individual, and controls, to a very great extent, the degree of constitutional reaction. My method has been tried out for five years at the New ,York Polyclinic Hospital, at the Newark Home for Crippled Children, in an extensive private practice, and in several years' experi- ence of a number of my colleagues, who have been kind enough to keep me constantly in touch with their work. It is at the request of these, and of the physicians who come to the Polyclinic Hospital for short courses in medicine, that I have set down the results of my experiences in written form. This volume will be as short and simple as possible, and will avoid all complicated theories and technicalities. Its aim is two-fold : It seeks first to unfold a method that will attract the general practitioner. I hope, in this way, to help in extending the field of tuberculin therapy far beyond the narrow scope of the specialists, as there cannot possibly PREFACE ix be enough specialists to reach the majority of sufferers from tuberculosis. My other aim is to reach those patients who have to continue their daily work while under treatment. We know that these are by far the vast majority and that they are the greatest menace in the spread of the disease. In short, I aim at an ambulatory treatment simple enough to reach physicians in every nook and corner, even where the best facilities are not at hand. I wish to express my appreciation of the works of those authors who have written so fully and convincingly on tuber- culosis and tuberculin for what they have done to make my experience possible. As my book is merely a practical guide to the use of the immune response in tuberculosis I could not at every point tell whether my idea arises from my own experience or from the reading of the literature on this sub- ject, and I did not interrupt my work to make the distinc- tion. So that if I failed to make frequent mention of those authorities in my work, it is not from lack of appreciation or from a desire to appear altogether original. To Doctor Charles Gottlieb for the excellent radiographs ; to Doctor .Sidney T winch for the material at the Newark Home for Crippled Children; and to my associates at the Xew York Polyclinic Medical School and Hospital for their assistance, I am greatly indebted. ELLIS BONIME. York, August, 1917. CONTEXTS PAGE FOREWORD By John Allen Wyeth, M.D., LL.D v PREFACE vii PART I Tuberculin in Diagnosis CHAPTER I INTRODUCTION -. . . . 1 Immunity Mechanism of Immunity Opsonins Antibodies CHAPTER II THE NATURE OP TUBERCULINS 7 Type 1, or Tubercular Filtrates Type 2, or Bacillary Bodies Type 3, or Type 1 and 2 Combined CHAPTER III CHOICE OF TUBERCULIN 12 Dilutions Directions for Making Dilutions Stability of Dilu- tions CHAPTER IV THE TUBERCULIN REACTION IN DIAGNOSIS 17 Indication for Tests Interpretation of the Tests Dosage Contraindications Determination of the Tuberculin Test Cutaneous Tests Escherich's Needle Tract Reaction Percu- taneous Test of Moro Intra-cutaneous Test Conjunctival Test Subcutaneous Tuberculin Test Symptoms of the Tuber- culin Constitutional Reaction PART II Tuberculin in Treatment CHAPTER I PAGE EQUIPMENT 42 Proper Record Sheets or Cards Syringe Needles Office Scales Containers for Dilutions Instructions to Patients CHAPTER II TUBERCULIN TREATMENT 51 Principles Underlying the Action of Tuberculin Scheme of Dosage Dosage Tables Intervals The Relation of Dosage to Individual Tolerance or Hypersusceptibility Advisability of Acquiring the Tuberculin Technique by First Treating Cases Where Severe Reactions Will Not Be Dangerous xii CONTENTS CHAPTER III PAGE TUBERCULOSIS OF THE GLANDS 68 Classification Closed Glands Open Glands Recurrent Glands After Radical Operation General Hypersusceptibility Begin- ning Treatment Conclusion of Treatment Results CHAPTER IV BONE AND JOINT TUBERCULOSIS 85 The General Consideration of the Complexity of Processes In- volved General Hypersusceptibility Beginning Treatment Conclusion of Treatment Results CHAPTER V RENAL TUBERCULOSIS 95 A General Consideration of the Present Status of This Form of the Disease General Hypersusceptibility Beginning Treat- ment Conclusion of Treatment CHAPTER VI PULMONARY TUBERCULOSIS 105 General Consideration Contra-indications To the Use of Tuberculin Classification Incipient Chronic or Slowly Pro- gressive Acute or Active General Hypersusceptibility Treat- ment Prognosis and Results CHAPTER VII MISCELLANEOUS TUBERCULAR CONDITIONS 132 Tuberculosis of the Pleura Tubercular Peritonitis Tubercu- losis of the Eye Tuberculosis of the Ear Tuberculosis of the Skin CHAPTER VIII SPECIAL CONDITIONS 142 The Constitutional Reaction in Treatment Tuberculin Intol- erance Abscess Formation Auto-inoculation Tri-monthly Tests PART III Special Treatment CHAPTER I PAGE INTRODUCTION "THE COMBINED THERAPY" 153 CHAPTER II MIXED INFECTION 157 Diagnosis of Infective Organism Smear Cultures Animal Inoculation Diagnosis by Physical Signs CONTENTS xiii CHAPTER III PAGE VACCINES 164 Preparation Standardization Containers Care of Vaccines Stock Vaccines Autogenous Vaccines CHAPTER IV TREATMENT OF MIXED INFECTIONS 173 Acute Mixed Infections Febrile and Afebrile Chronic Mixed Infections CHAPTER V MIXED INFECTIONS IN PULMONARY TUBERCULOSIS 184 Chronic Respiratory Mixed Infections Mixed Infections Which Follow Upon a Tubercular Process Mixed Infections Which Act as Fertilizer for the Tubercular Process Acute Respiratory Mixed Infections Treatment Prophylactic Immunization Against Mixed Infections Prophylactic Immunization Against Epidemic Infections Prophylactic Immunization Against Acute Exacerbations General Prophylaxis Elimination of Sources of Infection Personal Hygiene Dietetics CHAPTER Vl SURGICAL MEASURES 205 CHAPTER VII THE SURGICAL TREATMENT OF TUBERCULAR GLANDS 208 Soft Glands Suppurating Glands Cicatrized Glands CHAPTER VIII BONE CAVITIES, SINUSES AND FISTULAS 213 Mixed Infection Treatment CHAPTER IX BISMUTH PASTE 217 Composition of Bismuth Paste Bismuth Paste Injections Bismuth Paste Retention Frequency of Treatment The Proper Direction of Bismuth Paste Roentgenography CHAPTER X COLD ABSCESSES 226 Treatment CHAPTER XI EMPYEMA AND LUNG ABSCESS 231 Treatment Vaccines Against Infections Modified Surgical Measures for Drainage or for the Removal of Purulent Materi- als Local Treatment for .the Prevention of Reaccumulations of Purulent Materials and for the Stimulation of the Healing Process LIST OF ILLUSTRATIONS FIGURE PAGE 1 Tuberculin All-glass Syringe 14 2 Tuberculin Record Syringe 14 3 Bottles for Dilutions for Office Use (facing) 16 4 Bottles for Dilutions for Hospital Use (facing) 5 The Positive Von Pirquet Reaction (facing) 6 The Subcutaneous Tuberculin Test (Injection) (facing) 7 The Subcutaneous Tuberculin Test (Treatment of Puncture) % (facing) 40 8 The Subcutaneous Tuberculin Test (Local Reaction) . (facing) 40 9 Record Sheet (for History) 45 10 Record Sheet (for Tuberculin Record) 45 11 Chart I (Relation of Tuberculin to Patient's Tolerance) . . . (facing) 62 12 Chart II (Comparative Results of Methods of Tuberculin Administration) (facing) 63 13 Illustrates the Three Stages in One Individual : Glands ; Bone ; Lungs (facing) 68 14 Illustrates the Three Stages in a Child: Glands; Bones; Pul- monary (facing) 68 15 Illustrates the First and Second Stage: Glands of the Neck and Bone (facing) 70 16 An Example of Hard Cicatrized Glands After Connective Tis- sue Change (facing) 80 17 Shows the Difference Between a Radical Operation Before Tuberculin Treatment and a Cosmetic Operation After Tuberculin Treatment (facing) 80 18 Open Tubercular Glands (facing) 80 19 Open Tubercular Glands (facing) 80 20 Illustrates a Radical Operation With Extensive Recurrence a Few Months After the Operation (facing) 80 21 Illustrates a Radical Operation With Immediate Recurrence, With the Extension of the Process to the Apex of the Lung 80 22 Post-operative Recurrent Glands (facing) 80 23 Post-operative Recurrent Glands (facing) 80 24 Post-operative Recurrent Glands (facing) 84 25 The Effect of the Removal of a Local Lesion in a Constitu- tional Disease (facing) 88 26 The Effect of the Removal of a Local Lesion in a Constitu- tional Disease (facing) 94 27 Hip and Ankle Tuberculosis (facing) 96 28 X-ray Photograph of the Patient Shown in Fig. 27. .. (facing) 96 29 Shows the Same Patient as in Figs. 27 and 28, and Shows a Complete Cure (facing) 96 ILLUSTRATIONS xv FIGURE PAGE 30 Hip and Ankle Tuberculosis (facing) 96 31 X-ray of the Same Patient as Fig. 30 (facing) 96 32 Hip Disease and Tubercular Peritonitis (facing) 96 33 X-ray of the Same Patient as Fig. 32, Which Shows the Ex- tent of the Tubercular Process in the Hip (facing) 96 34 Shows the Healed Condition of the Same Patient as Fig. 32. . (facing) 96 35 X-ray of Chest (Pulmonary Tuberculosis) (facing) 124 36 X-ray of Chest (Same Patient as Fig. 35, Ten Months Later) (facing) 128 37 X-ray of Chest (Acute Febrile Pulmonary Tuberculosis) (facing) 130 38 X-ray of Hour-glass Stomach (Tubercular Peritonitis) (facing) 136 39 Temperature Chart (Determination of Constitutional Reac- tion) 143 40 Temperature Chart (Effect of Contagious Disease of Hyper- susceptibility) 151 41 Temperature Chart (Effect of Contagious Disease on Hyper- susceptibility) 152 42 Pyogenic Bacteria, Methylene Blue Stain (facing) 160 43 Containers for Vaccine (facing) 166 44 Taking of Vaccine from Container (facing) 166 45 Temperature Chart (Relation of Vaccine Administration to Temperature Curve) (facing) 176 46 X-ray of Chest (Circumscribed Mixed Infection) (facing) 202 47 X-ray of Chest (Slowly Progressive Tubercular Lesions, the Mixed Infection Preventing Complete Healing) . . (facing) 202 48 X-ray of Chest (Tubercular Process Superimposed on Chronic Mixed Infection) (facing) 204 49 Cut of Knife 209 50 Proper Direction of Bismuth Paste (Schematic Drawing) (facing) 224 51 Proper Direction of Bismuth Paste (X-ray at Beginning of Treatment) (facing) 224 52 Proper Direction of Bismuth Paste (Fig. 51 at Conclusion of Treatment) (facing) 224 53 Proper Direction of Bismuth Paste (X-ray of Tubercular Hip) (facing) 224 54 Proper Direction of Bismuth Paste (Photograph of Fig. 53) . . (facing) 224 55 Proper Direction of Bismuth Paste (Tubercular Coxitis) (facing) 224 56 A Pulmonary Abscess Draining Into the Pleura and Produc- ing an Empyema (facing) 234 57 A Pulmonary Abscess Draining Into a Bronchus (facing) 236 58 A Pulmonary Abscess Draining Into a Bronchus and Into the Pleura (facing) 236 59 An Extra-pleural Abscess Previously Diagnosed and Treated as Empyema Complicating Pulmonary Tuberculosis (facing) 238 PART I CHAPTER I INTKODUCTION Excepting instances of the immunity, which is natural or hereditary, and the passive immunity, where the infec- immunity is . i -i always the tion was in some other animal, all immunity is the result resu it of of infection which stimulated the body cells to the formation inectlon - of specific antibodies. The infection may. either be caused by living bacteria, virulent or avirulent, or to a milder degree by dead bacteria. The word " immunity," as generally understood, means a state of the organism as resisting a special invasion, but immunity we must include the mechanism by which this state is f [" m s ^ acquired in its broader meaning. When such an invasion process going occurs, either by the micro-organism or by a physical or establishment chemical cause, the normal physiological processes of the of the state of * " resistance to body are interfered with and physical and chemical changes the particular immediately take place in the organism to counteract it; and when this counteraction is accomplished, changes again take place which gradually reinstate the normal processes. The defensive processes, plus the natural tendency to return to normal, are included in the mechanism of immu- nity, so that, whether toxic substances or bacterial substances have formed the abnormal state, the gradual return to normal is the immunity acquired, whether it be a toxic immunity or a bacterial immunity. In the case of infections, we may have a bacterial The immunity . , , . , , . . . . , may be against immunity to deal with that is, an immunity against the the organ i sms direct action of the bacteria ; or, we may have a toxic or its toxins or . . . both - immunity to deal with that is, the acquirement of immu- nity against toxic substances which the bacteria liberate, either through their metabolism or through their death; or, we may have a combination of the two that is, we may have an invading organism which not only does harm by its 1 TUBERCULIN AND VACCINE Where the two exist treatment is complicated. Active immunity and passive immunity. A combination of the two advisable in suitable cases. The protective mechanism of the host consists of two elements; the Phagocytes and multiplication and extension in the tissues, but may also produce toxic substances which in themselves form protein poisons, doing damage to the organism. It is in this latter form that treatment seems most diffi- cult, as the established use of vaccines, while active against the organism, fails to produce any results against the toxicity. On the other hand, the use of antitoxins, while neutralizing this toxic substance, still allows the bacteria to multiply and produce more toxicity and direct damage by their presence. There are two ways in which the organism can acquire immunity. One -way is by the natural physiological process in the organism, whether set in motion by the organism directly, or whether stimulated by outside agencies. This is called active immunity. However, the discovery was made that the sera of immunized animals retained the immune substances which we are able to transfer to the sera of other animals, thus merely placing immunity into the circulation without the necessity on the part of the recipient to form his own immune substances. This was called passive immunity. It might be well at this point to bring out the fact that one form of immunity does not preclude the other in the same organism against the same infection. We can stimu- late the mechanism of the immunity in a given individual by certain substances and find this stimulation either too slow or insufficient and so use a passive immunizer at the same time. The Mechanism of Immunity Since the protective mechanism of the host is specific against each organism, we can easily see how extremely complicated and for the most part theoretical our present knowledge of the subject still remains. However, the two most important methods of protection stand out very prominently. The first and most far-reaching is the mechanism of phagocytosis with the production of substances which render the invader amenable to phagocytic action. INTRODUCTION 3 The second protective process deals with the formation Antibodies of substances in the blood stream and in the body sera that act directly on the invader in various ways, to destroy or neutralize the poisons of the invader. Taking; up the subject of phagocvtosis in detail, we find The P ha s- r " cytesandthe that in order that it prove effective at all, substances must opsonins which form which combine with the invader to render it absolutely c a t ion possible susceptible to phagocytic action. These substances we call opsonins. These opsonins are negative to each invader and the amount of protection they give the host is in direct propor- tion to its quantitative existence at the time of invasion. This fact has brought out the subject of opsonic index. Wright has found that the amount of opsonins present in Determination ,.,..,, . . . , of amount of each individual at the time of invasion can be determined ; protection, thus, a measure for the amount of protection on the part of the host is at hand. By this measure we are able to deter- mine at any given moment during an invasion, whether the host or the invader has the better of the combat; and it has been undertaken to constantly measure this protection in order to determine the period for rendering outside assis- tance to the host. Further work in vaccine therapy has shown that clinical symptoms are sufficient to indicate both the necessity and the intervals for outside interference, making this tedious and highly specialized process of opsonic index determination ppsonic unnecessary. This is rather fortunate; for, if the treatment unnecessary, with vaccines depended on the determination of the opsonic index, vaccine therapy would have died out completely, or smouldered in the hands of the few. Opsonins. There are two conditions absolutely neces- sary for opsonins to play an effective part in the course of the infection. First, the bacterial invader must be suscep- Conditions for tible to opsonic action, and secondly leucocytes, capable of active phagocytic action upon the opsonized bacteria, must be present. The number of staphylococci taken up by 100 leucocytes opsonic veness. 4 TUBERCULIN AND VACCINE in a mixture of leucocytes, staphylococci and serum of the patients suffering from furunculosis may be 200. In a smaller mixture of normal serum, under the same conditions, 100 leucocytes may contain 400 staphylococci. Method of Wright found from repeated determinations of the opsonic index . .. determination opsonic index that a curve niay be plotted which has the which proved nr enera l characteristics of other antibodies. The curve may that small doses of vaccine be modified by the inoculation of small amounts of culture of the organism causing the infection. The course of the curve depends on the amount and toxicity of the dose ; thus small doses tend to raise the curve. A larger inoculation causes first a depression of the curve below normal (negative phase) and then increases it to a point considerably higher than before (positive phase). If the amount of inoculation is still larger, the negative phase is more marked and of abnormal duration; and may or may not be followed by a positive phase depending upon the amount of excess dosage. The aim of small doses of vaccine, such as would give the maximum dose of opsonic response and the necessity of giving doses at sufficient intervals of time to allow of the development of the maximum reaction from previous inocu- lation, were repeatedly emphasized by Wright. Antibodies. In dealing with the second form of pro- tection, in which the substances act directly on the invading organism, we have three distinct forms : in the immune I n the first place, we have substances which tend to response there , . .. / i i mi is a production paralyze the activity of the invading organism. Ihese sub- O f substances stances are known as precipitins and agglutinins. acting directly on the invader. Second, we have substances combining chemically with the bacteria, causing them to disintegrate. This class of antibodies is known as lysins. Third, we have substances neutralizing the toxins set free by the bacteria, the substances being designated as antitoxins. Vaughn and others have shown that if bacteria are digested by chemical means or by treatment with the bac- teriological serum, that the toxicity of the suspension is INTRODUCTION 5 enormously increased. The inoculation of such a suspension in animals was observed to produce highly toxic symptoms. Thus, the host may produce a digestive substance as a part of the defensive mechanism, that is, for the diges- tion of the bacteria which might produce a very highly toxic combination and which, in its absorption, may seriously injure the host; or, it may cause a local proteolysis of the host's own tissues. Or, the defensive substances (anti- bodies) produced by the immune response, in combining chemically with the invading organisms (bacteria) may The end- form proteins which are highly toxic to the host. un'i Proteins .derived from the action of antibodies upon body with the i , i'ii -pit invader may bacteria may become highly toxic to the host 11 the host be toxic to possesses a hypersusceptibility (idiosyncrasy) to these pro- ^oTfiT" 1 "* 1 terns. " Anaphylaxis " is the term applied to the syndrome sensitive to complex produced by the action of these proteins in hyper- sensitive individuals; while /" allergy " is the term applied to the state of hypersusceptibility produced in an animal, making the production of " anaphylaxis " possible. The most prominent example of " allergy " exists in tubercular individuals. The infection with the tubercle bacillus is almost universal ; but a prompt immune response puts an end to its activity early in life. However, those individuals possessing or acquiring idio- syncrasy or hypersusceptibility to the proteins produced during the immune response, are subject to a more success- ful invasion by the tubercle bacilli. For, should an inva- Hypersus- sion occur, whether it be by new bacteria or an extension responsible" from an old focus, the consequent immune response giving for the i . i ' i i i' i i ! !! development rise to the protein to which the individual is susceptible, will O f tuberculosis. produce a toxic or an anaphylactic effect. This effect, when brought about by an artificial immune response, is better known as " the constitutional reaction." Such a constitu- tional effect momentarily lowers the resistance of the individ- ual to the invader, in this case the tubercle bacillus ; and so allows of its multiplication and extension into the tissues. Whereas, in most of the common infections to which the TUBERCULIN AND VACCINE The vicious cycle in tubercular affections: The protective response pro- duces toxic protein which allows of extension of the disease. The vicious cycle is responsible for the neglect of tuberculin. The aim of this book. human race is subject, we aim to obtain a maximum amount of immune response, in the infection with the tubercle ba- cillus its severity depends upon the greater immune response. The vicious cycle in tuberculosis is thus made plain. The only means of defense against tubercle bacilli is the immune response; but, owing to the presence of hypersusceptibility, the proteins produced by the immune response poison the individual, allowing of a further extension of the disease. Thus, a vigorous immune response which is curative in other diseases, would tend, in tuberculosis, to produce the active or hasty form of the disease, and the more gradual immune response tends towards the chronicity of the process. So it has come to pass, that, although no one any longer denies that tuberculin is capable of eliciting an immune response, with an easily ^demonstrable hyperemia in the diseased tissues, it has been abandoned and even condemned in the treatment of tuberculosis. Fortunately, there is an increasing number among the profession who have learned that we may acquire a tolerance to a protein poison, and overcome the individual hypersus- ceptibility, if we produce a slowly increased amount of tol- erance by means of a gradual, artificially stimulated, im- mune response, with the degree of individual hypersuscepti- bility as an index. The principal aim of this book is to emphasize the necessity of overcoming hypersusceptibility and to advocate the utilization of the immune response in tuberculosis, and to do this by a method sufficiently simple to become prac- tical in the hands of the general practitioner. For it is the general practitioner alone who is able to reach the great numbers of sufferers, and to reach them in the earliest stages of the disease. Incidentally, lest our successes prove often useless to the afflicted, I have added, in some detail, methods by which we may remove, or at least modify the results of the tubercular affection, obtained before the patients pre- sented themselves for treatment, I am referring to the part under " Special Treatment." CHAPTER II THE NATURE OF TUBERCULINS The specific remedies for tubercular affections have the same aim as products aiming to produce immunity in all Tuberculins . . . . are modified other affections ; that is, active immunity and passive im- vaccines, munity. We are mainly concerned with the former. The passive form consists of products cropping up here and there, and aiming at a more direct attack against the scourge, by producing passive immunity. The passive method of immunity in tuberculosis is thus far in the experimental stage and nothing brought forward, up to this time, gives any promise of antitoxic value. How- ever, we should bear in mind the prevalence of the disease, keeping our minds open to conviction, taking account of Antitoxins for tubercular every product that may be brought forward through scien- affections have tific research, in order not to overlook, bv too hasty iudg- sofarno * f * ' proved effective. ment, that remedy, which through the induction of passive However, we immunity, can alone solve the world-wide problem involved. r econeived W We must not allow ourselves to forget that only with a pas- prejudice to .7, ; , . . retard the sive immunizer can we do away with the hypersensitiveness progress of in tubercular subjects with one stroke, and either cure the r patient with it alone, or augment the treatment with an active immunizer, such as we now use, without the fear of reaction, producing the same results as we are now obtaining with vaccine in other infections. The following are the three most important antitoxins, or antitoxic sera that have been brought out, and which have up to this time gained the widest publicity: Maradeano's Serum. Three of the most important Marmorek's Antituberculosis Serum. antitoxic sera Hoechst's Tuberculosis Serum. S o f ar. Each of these, and several of the others which we need not mention here, have raised the hopes of their particular inves- 8 TUBERCULIN AND VACCINE There are three main Tariations in tuberculins. Old Tuberculin OT or T. Tuberkulin obers alt TOA. tigators, but as jet, no passive immunizer has been discov- ered which can be recommended for general use. Of the active immunizers, with which we are here con- cerned, we have the three chief forms as exemplified by Koch's original work and which still represent the basis of all other forms and modifications subsequently produced by others. These products consist of three principal varieties : (1) the soluble .secretions of the tubercle bacilli, (2) the bacterial bodies alone, and (3) a mixture of the two. All other preparations, whether derived by Koch himself or by others, merely depend on the method of preparation or con- centration, or upon the method of sterilization which takes into account the variations in the extraneous substance, going into the solution from the culture media. Type 1, or Tubercular Filtrates Koch's OT, AT (alt Tuberkulin) or T, is the most familiar and best example of this type. Its method of preparation is as follows: Pure cultures of tubercle bacilli are grown from four to six weeks on a 5% glycerine-broth. This is sterilized with the culture fluid by heating for one hour in steam. This is filtered, removing the tubercle bacilli from the liquid, which is now con- centrated to one-tenth its bulk in a low temperature oven. It thus consists mainly of the soluable secretions of the tubercle bacilli, plus a small amount of endotoxin, which is extracted from the tubercle bacilli bodies during the hour of steam sterilization, owing to the presence of alkali and glycerine in the medium. TOA (Tuberkulin obers alt) is the same as OT, except that it is not concentrated to one-tenth its bulk. When used, it is merely taken in ten times the strength as OT, using a IS T o. 4 dilution where No. 5 of OT would be used and so on throughout the dilutions. Its advantage over OT, 9 if any, consists only in having to make one dilution less at the beginning of the treatment, but has its great disadvan- tage at the conclusion of treatment, when a full c.c. and then 2 c.c. of the pure TOA would have to be administered. It is. however, a favorite in some parts of Europe, especially in Switzerland. AF (albumose-free Tuberculin) is the same as OT, except that the bacilli are grown in an albumose-free medium. It is claimed that it has the advantage of pro- ducing less fever during a reaction by the removal of the albumose, which is one of the factors in producing fever. All >umose-free ' . m tuberculin AF. It would, therefore, be well suited for a case with extreme hypersusceptibility, at the beginning of treatment. How- ever, it is extremely difficult to get a constant product, disastrous results having occurred during treatment by a variation in its strength. And it is doubtful whether the quantity of albumose, during treatment, is a factor at all in the production of the constitutional reaction and so, it is best to leave these more difficult products until such a time, when our experience will allow of experimentation. Type 2, or Bacillary Bodies The dry tubercle bacilli in a watery emulsion were first used, but found to be impracticable, because the bacillary bodies proved to be non-absorbable in the tissues, and soon formed localized abscesses. Pulverization of the dried bacil- lary bodies was found necessary, and so the best example of this type was produced by Koch, i.e. BE or bacillary emulsion. The tubercle bacilli are removed from the culture Bacillus Emulsion BE. medium after sufficient growth, carefully washed, dried and then pulverized. An emulsion is made, by adding one part of pulverized tubercle bacilli, to a hundred parts of a solution composed of equal parts of water and glycerine. This is tested for the presence of living tubercle bacilli, and when found sterile, is ready to be used. 10 TUBERCULIN AND VACCINE Tubercular TK and TO (Tubercular Residue or New Tuberculin New Tuber- and Tubercular Obers) are both derived during the process of emulsifying the BE. The pulverized tubercle bacilli Tubercular are shaken in the water and allowed to stand until they fall in a sediment The water is decanted from the top and used as a tuberculin, which is designated as TO. The sediment is emulsified with equal parts water and glycerine in the same manner as BE, and is designated as TR or new tuber- culin. Both of these were found extremely inconstant in strength and were soon abandoned. SEE or sensitized BE, or as manufactured by the Hoechst Farbwerke, under the name of " Tuberkulose-Sero-Vakzin," is an attempt to remove the toxic principle of the tubercle sensitized BE bacilli by a specific amboceptor (Antituberculin) by allow- S B E or " Tuberkuiose- ing the pulverized or whole tubercle bacilli to remain in Farb'Je^ke-" contact with a tubercular serum. Striking results have Hoechst. been obtained with this sensitized BE, especially in animal experiments, but it is found that this tuberculin is much more active than any of the others, requiring a sixth or even seventh dilution at the beginning of treatment. Besides the drawback of being much stronger in its effect upon the organism, it is not stable, becoming stronger as it grows older; and it is also very expensive. Type 3, or Type 1 and 2 Combined Tubercuioi The best example of this type is Tuberculol Landsmann. Landsmann . . a good example This is prepared by making a BE and adding this to the fil- f combined." trate w ^^ c ^ nas ^ )eerL concentrated in vacuo as far as possible. It now undergoes a process of filtration through porcelain candles, and after the addition of phenol to a five per cent, strength, it is diluted until 1 c.c. is a lethal dose to a guinea- pig weighing 250 gnn. A more detailed description of the method of preparation may be found Landsmann. Zentralblatt fur Bakteriologie, Bd. xxvii, 1900. Hygienische Rundschau, 1898 Nr. 10 u. 1900, Nr. 8. THE NATURE OF TUBERCULINS 11 This tuberculin has the advantage of being absolutely constant in its amount of tuberculin reactivity, as every sample is tested to a given lethal strength. It is, however, highly toxic and very difficult to handle in the beginning of treatment. If used at all, it should be resorted to after a high degree of tolerance has been acquired through the use of OT. In the conclusion of treatment, it is to be highly recommended together with the suggestion of Landsmann, that the final dose should be repeated at constantly increas- ing intervals for a considerable period of time in order to maintain a maximum amount of tolerance acquired through its use. Wolff-Eisner directly mixed OT and TR. Klebs and Beraneck (TBk) have made similar mixtures. A whole byBeran series of preparations have been made by Spengler, mixing others, the OT and BE in different proportions intended for differ- ent grades of hypersusceptibility. Gabrilowitsch made his " Endotin " claiming to have removed the toxic substances from tuberculin, in order to prevent the constitutional febrile reaction, but all these merely represent tuberculins made weaker, for it is the amount of immune response, and not the toxic substances in the tuberculin, which is responsible for the febrile reaction. In the resume of the principles involved in the various forms of tuberculin, my aim has been to allow of a glimpse into their differences, in order to simplify the matter and remove the idea which total ignorance of these various products might bring about; i.e., the feeling that there may be something still better than what we are already using, so that we shall not be tempted to try a host of different preparations without having given any one a fair trial. As I have said before, we can do far more with 'a tuberculin that may not be the best, but with which we have a long experience, than we can with the best products and with constant change. CHAPTER III CHOICE OF TUBEKCULItf From innumerable investigations and from reports from different clinics, it is now established that Old Tuberculin is distinct from other tuberculins, in that it possesses that element which brings about the maximum amount of toler- ance to protein poison and also produces a maximum amount of focal reaction or hyperemia. This is because OT does not contain the bacillary bodies. Any tuberculin that contains the bacillary bodies, seems to bring about a greater immunity against the tubercle bacillus. OT is best for It thus produces more antibodies, and causes disintegration O f focal of a larger number of tubercle bacilli. Since the protein hyperemia. poison comes from the tubercle bacilli thus killed, it is com- prehensible that too great an amount of poison is elaborated by any tuberculin containing the bacillary bodies, making it difficult to gain tolerance to the bacillary poison, and making it extremely liable to severe and dangerous reactions. OT has a Old Tuberculin contains a, minimum amount of substance !maii V amount stimulating the formation of antibodies. Hence, it can be of substance safely used, because we can more easily control the amount stimulating . . . antibody for- of antibodies and the number of tubercle bacilli killed, and in that way we can control the amount of poison these lysinized easil x tubercle bacilli form. We must not lose sight of the fact that for a cure, to be complete, bacillary immunity must be gained as well as tolerance. Consequently, the bacillary bodies are of great value in this connection after OT has been used to the optimum dose; a dose sufficiently large to establish the fact Any emulsion fort Wpersusceptibilitv has been removed. of tubercle * baciiii can act It follows that the ideal choice of tuberculin would be "ccine C when r to use ^ until the maximum dose is reached, at which hypersuscepti- point the patient shall have acquired complete toxic im- bility is . removed. munitv and in a large percentage of cases complete healing. CHOICE OF TUBEKCULINS 13 Should the necessity of further treatment be indicated, the ideal situation is present for the use of a bacillary emul- sion. The toxic immunity need not be reckoned with any further and bacterial immunity can now be established in the same manner, as with any vaccine. Dilutions As regards the making of dilutions, as simple as the The usual method matter may seem, a great deal of confusion is produced in of making the minds of those who set out to use tuberculin. This compHcaTe'd for confusion is caused not only by difference in methods every-day use. expounded, but also by the standard of measures used in naming the quantities of tuberculin. Thus, some authorities measure by weight, others by There should volume. Now, the former requires a knowledge of the standard of amount of the solid substance in the specific tuberculin measu f ement for tuberculins. used. This knowledge is difficult to obtain in a great many instances and very often varies according to the different authorities. The volume of the tuberculin, on the other hand, always remains the ^ame, and should therefore be the standard of measure in making dilutions. Again, in making dilutions in multiples of ten, one easily Make ail the reaches the highest dilutions, such as 1 in a million, or 1 t he U requ!red in ten-million, without the least difficultv. This method is one instead of ' . ,.,,., attempting to certainly less difficult and infinitely more accurate than at- make the tempting to make the dilution which one requires for use directly. Again, the advice given for the luse of various measuring glasses, pipettes, graduate cylinders, etc., adds to the size of the mountain in the imagination of the beginner, when The use of a only a mole hill is in question. Since, in order to practice tuberculin accuracy in tuberculin treatment, we must use a finely sub- syringe, the i > i i i i , . . same as is divided tuberculin syringe, why not use the same syringe used in treat- in making dilutions and thus simplify the whole process? a ^ e d n si 1 m b 1 e e s s t t A good tuberculin syringe should consist of all glass, or an for dilutions. accurately fitted metal piston in a glass barrel holding 14 TUBERCULIN AND VACCINE y, per cent carbolic in normal saline is best as diluent. one c.c. divided into tenths and each tenth subdivided into five or ten parts. Each division therefore holds 0.1 c.c,, and each subdivision holds 0.02 c.c. or 0.01 c.c. The diluent used in making the dilutions is a half of one per cent carbolic in normal saline (i.e., one drachm of a 5% carbolic solution added to 9 drachms of sterile normal saline placed in a sterile bottle). This may be used until the appearance of a fungus, when fresh diluent should be made. FIG. 1. Tuberculin all-glass syringe. FIG. 2. Tuberculine record syringe. Directions for Making Dilutions Five wide mouthed bottles holding about a dram each should be numbered 1, 2, 3, 4, 5. (See Fig. 0.) Draw into a tuberculin syringe 0.9 c.c. of the diluent followed by 0.1 c.c. of the tuberculin. This makes the first dilution. Put this into bottle marked 1. Draw in 0.9 c.c. diluent followed by 0.1 c.c. from bot- tle 1. This makes dilution 2 which should be placed in bottle labeled 2. Draw in 0.9 c.c. of the diluent followed by 0.1 c.c from bottle 2. This makes dilution 3 which is put into bottle labeled 3. Draw in 0.9 c.c. of diluent followed by 0.1 c.c. from bottle 3. This makes dilution 4 which is placed in bottle 4. Draw in 0.9 c.c. diluent followed by 0.1 c.c. from bottle 4. This makes dilution 5 and is put into bottle labeled 5. CHOICE OF TUBERCULINS 15 Special stress is laid on the drawing of diluent into the syringe first, followed by the tuberculin or its various dilu- tions. There are two good reasons for this : First : The first division of the syringe is not reliable and varies with the size of the needle or the shoulder of the syringe. Thus, measurement of the tuberculin will not be accurate. Second : In expelling the mixture into its respective numbered receptacle, the tuberculin leaves the syringe first, followed by the diluent, so that if any remains in the needle or shoulder of the syringe, it will be diluting fluid, and no tuberculin will be lost. This will also obviate the necessity of rinsing the syringe after each dilution. Strength Pure Tuberculin in Dilution of Dilution each c.c. of Dilution Xo. 1 contains 1 in 10 or 0.1 c.c. or 100 c.rnm Xo. 2 contains 1 in 100 or 0.01 c.c. or 10 c.mm Xo. 3 contains 1 in 1,000 or 0.001 c.c. or 1 c.mm No. 4 contains 1 in 10,000 or 0.0001 c.c. or 0.1 c.mm Xo. 5 contains 1 in 100,000 or 0.00001 c.c. or 0.01 c.mm Stability of Dilutions A diversity of opinion seems to exist regarding the sta- bility of the various dilutions. To determine exactly the length of time that each dilution would remain active, would not be at all worth while. It would involve a great sacri- fice of time and energy, requiring a mass of laboratory tests Dilutions and animal experiments, with results that would be prac- mad'J'f rh on tically of no scientific value. The only value would be the day of use. from an economic standpoint ; and this is a very insufficient reason for the waste of time and effort, as the cost of tuber- culin, when made up in dilutions, is insignificant. Besides, as is made evident by the foregoing methods of making dilu- tions, there would hardly be a saving of labor for those having to make up the dilutions for treatment. I take this occasion to condemn the use of prepared 16 TUBERCULIN AND VACCINE Ready made dilutions should be avoided. dilutions put up at distant laboratories, and by men who are not in touch with the patients. No one will fail to feel a degree of gratification from the knowledge of tuberculin such as may be derived from the handling of it, and to acquire an exactness that comes with making one's own dilutions. After making these dilutions once or twice the utter simplicity of this method becomes apparent. NOTE: Solution No. 1, if kept two or three weeks in a dark cool place and if no precipitate forms, will remain stable that length of time. It is well to keep what remains over from No. 1 dilution until just before making the next dilutions. Occasionally there will be an unexpected delay in obtaining the original pure tuberculin and the left over No. 1 can be used in such an emergency. II "3 CHAPTER IV THE TUBERCULIN REACTION IN DIAGNOSIS Following the tendency of all things to go in the direction of least resistance, the medical profession has usually tended to avail itself of the easiest way and the nearest elements at hand to help in the diagnosis of disease. With the extended The ease of j*i T i T -i application use oi tuberculin, this inclination may result in a too should not ready employment of this agent as a means of diagnosis, Indiscriminate since its ease of application !will tempt the diagnostician use of the much more readily than will the routine of physical exam- test . ination or the examination of sputum, systoscopic examina- tion, catherization of the ureters, Roentgenographic exam- inations or other means, many of which require the sending of the patients to a distant laboratory, and all of which demand the consumption of valuable time. This condition may lead to the abuse of the tuberculous, so let me emphasize at the outset that a tuberculin consti- tutional reaction heightens the hypersusceptibility of the patient, and so increases the difficulty with tuberculin treat- A severe ment in proportion to the severity of the constitutional reac- reactumwiii tion thus brought about. As far as the local tuberculin reac- increa s the , . . . difficulty of tions are concerned, there is -no harm in their utilization tuberculin whenever desired, with the exception of the conjunctival test t of which I shall speak under a separate heading. But, in the case of a test which requires a constitutional reaction for its value in diagnosis, tuberculin must be used only as a whiiethe method of last resort. So long as we have means at hand to are harmless, establish a diagnosis without tuberculin, so long should we the c nstltu ; tional reaction avoid its use. By adhering to this maxim, we shall make as a test use of the constitutional reaction in diagnosis only in the utilized as a very early stages of the disease, where all other methods of lastresort diagnosis have failed, or have failed to produce definite find- ings. We shall then be applying it in cases where even with a severer constitutional reaction the damage will not be great. 2 18 TUBERCULIN AND VACCINE The ability to recognize the phenomena of the tuberculin reaction will grow with experience, thus constantly increasing the value of tuberculin in diagnosis. All tuberculin reactions have the infallible quality of detecting the presence or absence of hypersus- ceptibility. hence Its greatest importance will be recognized when an effective prophylatis will obtain universal application. Once the proper place of tuberculin in diagnosis is estab- lished, it becomes a valuable asset in our hands; for, by its means we shall be able to discover early processes which have been impossible of discovery without tuberculin, yet which, when discovered are the most amenable to the tuber- culin treatment. The more frequently tuberculin is used in diagnosis, and the longer the phenomena connected with the reaction it produces are studied, the greater becomes its value in the diagnosis of tuberculosis and the more devoid of any damage to the patient. The tuberculin reaction is essentially a reaction to hypersusceptibility. Whether, as I shall explain further, any one of the methods of the utilization of tuberculin in diagnosis enables us to discover an active lesion or not, it is certain that they all detect hypersusceptibility which means the presence of a tubercular lesion healed or other- wise somewhere in the body, with the possibility constantly present of an extension or reawakening of the process some time in the future. This is why the tuberculin method of detecting individual hypersusceptibility is destined to be- come the greatest instrument for the ultimate prophylactic treatment against this dread disease, for it will be the means of distinguishing the individuals requiring such prophylaxis from those who are naturally immune to tuberculosis. There are hundreds of reports in the literature of tuber- culin such as those of Binswanger and those from the army recruiting stations in various parts of Europe, all of which leave no room for doubt that all individuals destined to succumb to tuberculosis would be found by means of a tuber- culin test to possess hypersusceptibility ; whereas the natural immunity exists among those who do not possess such hyper- susceptibility. Indication for Tests The indications for the use of the tests divide the various tests into two groups. The tests which aim to produce a localized reaction only may be indicated in THE TUBERCULIN REACTION IN DIAGNOSIS 19 any case and may be used as often as desired, for they leave very little, if any, effect upon the patient. The only exception is the conjunctival test, of which I shall special speak later. On the other hand, the indications for the need be use of the constitutional reaction in making the test should co " slder d only in the be carefully considered before it is applied. Thus it should case of the be applied only as a last resort method of diagnosis, and test only in such a way as will no.t jeopardize the status of the case with reference to tuberculin treatment, if it should be determined upon. Interpretation of the Tests Since the object of tuberculin diagnosis is to discover other phe- ,. , . ,, .. , , T nomena occur- active disease, and since the reaction to tuberculin is a ring durin g a reaction to hypersusoeptibility alone, Iwe must take into reactlon account other manifestations occurring during the reac- diagnostic of tion in order to derive the full benefit of the diagnostic except i^very value that the various tests possess. In the case of the young children 1-1 -11 T j? where the localized reaction, we can consider them diagnostic 01 ac- mere presence tive tuberculosis only in such cases where hypersuscepti- s bility must exist together with the active form of the dis- sufficient. ease ; in other words, in cases where the process had no time to heal. This can be true only in children up to three, perhaps four years of age. The tubercular process when only suspected (thus requiring this test) is bound to be the first process attacking the child, and so the mere presence of hypersusceptibility is sufficient to establish the diagnosis A focal of active tuberculosis. Under these circumstances, any test '*" 13 bringing about a local reaction alone is sufficient. But, even with the when dealing with an older individual, where a slight lesion constitutional healed and was not noticed previous to the present suspected r attack, the detection of hypersusceptibility is not helpful in the determination of the diagnosis. Fortunately how- ever mild the reaction may be, there always occurs a hyper- emia around the lesion during the time of constitutional manifestations of the reactions and thereby renders it valu- able in the detection of an active lesion. 20 TUBERCULIN AND ^ 7 'ACCINE The focal reaction or the hyperemia can only occur in the tissue which is the seat of active disease, thereby increasing physical signs and symp- toms originat- ing in such tissues. A negative cutaneous test obviates a series of subcutaneous tests. This hyperemia or focal reaction as it is called, produces an increase of the inflammatory process in the lesion, and in that way exaggerates any symptoms or signs which its locali- zation in the body would otherwise produce. Such exaggera- tion is all that is necessary to remove the doubt that existed with regard to the nature of the condition that made the test necessary. Thus, indefinite physical signs at the apex of the lung will become definite during the constitutional reaction. Rales will become more prominent, dullness more definite, etc. The patient will complain of increased cough and expectoration. During this time the sputum may show tubercle bacilli, whereas before, repeated examinations failed to demonstrate them. Suspected mediastinal glands may make themselves more prominent by a slight swelling that is produced with a focal reaction ,during the constitutional reaction. Such swelling would produce pressure in the chest, a sensation of fullness behind the sternum and even dyspnea. The hyperemia produced in glands of the neck will render them more tender during the reaction, thus establishing the fact that they are tubercular. Urinary symptoms may be increased and even tubercle bacilli demonstrated in suspected genito-urinary tuberculosis during a constitutional reaction ; and so on through the list. - The fact that the absence of hypersusceptibility excludes a tubercular lesion, might make it advisable to establish the fact of the presence of hypersusceptibility by (the simpler local test before the subcutaneous *test is resorted to. In that way we might occasionally spare the patient hypodermic injections of tuberculin by ruling out hypersusceptibility. The dose of tuberculin generally advised aims to produce a constitutional reaction in all cases and is Dosage In a constitutional tuberculin test for the diagnosis of tuberculosis, the subcutaneous method is the only one where the consideration of the amount of tuberculin is necessary, as the amount of tuberculin used in the localized test is unim- portant. The constitutional reaction varies in severity in THE TUBERCULIN REACTION IN DIAGNOSIS 21 proportion to the amount of tuberculin used, plus the degree con sequenti y too large for of hypersusceptibility present. Most writers on the subject some. of tuberculin diagnosis* advise a dose of tuberculin which ex- perience has shown produces a constitutional effect in all cases where a tubercular process is present. They give consideration to this subject with only one aitm in view, and that is, to pro- duce a reaction for diagnostic purposes and take no cogniz- ance at all of a contemplated treatment with tuberculin in case the test establishes a diagnosis of an active lesion. I believe that such an attitude is not to be recommended even without the contemplation of tuberculin treatment; for, if a constant quantity is used for all cases, the constitutional reaction will vary in proportion to the degree of hypersus- ceptibility in the individual, and if such a quantity is cal- culated to produce a constitutional reaction in an individual with a small amount of hypersusceptibility, it will be very severe in those who possess a higher degree of hypersus- ceptibility. In the latter case, whatever the contemplated treatment Th e severe may be, the chances for recovery in such an individual have duced during been greatly diminished. Not only does a severe constitu- f testha y e increased the tional reaction produce great harm to the afflicted, but helps prejudice greatly to increase the prejudice against tuberculin treat- cun'n^reatmen ment; for, here again the apparent fault in the production of the harm is with the tuberculin; w r hereas the real fault lies with the quantity of tuberculin used. Severe reactions have also helped to produce an array contra- of contraindications to the tuberculin test which should reallv be considered as centra-indications to severe tuber- constitutional i " 11 T i i i reaction dis- culin reactions, and when a limitation is placed on the appear with amount of constitutional reaction for the purpose of diag- nosis, all these contra-indications will lose their purpose, dosage. When a patient presents himself for the diagnosis of tuberculosis, and the importance of establishing a positive or a negative diagnosis is explained, it will be a great excep- tion if such a patient object to two or three or even four 22 TUBERCULIN AND VACCINE tests, especially when the safety of such a procedure and the danger of the single test method is pointed out. The quantity ^he amount of tuberculin to be used in a subcutane- of tuberculin . used for a ous test should be no more than ten times the quantity diagnostic j. ^ used. > in such form of tuberculosis as is recom- constitutional reaction should me nded as the beginning dose in its treatment. (See page 23.) For example: If a pulmonary lesion is suspected and ' 10 C ' C ' of ^ e fifth dilution is tne dose for tne beginning of mentofthe the treatment of pulmonary tuberculosis, 0.10 c.c of the fourth dilution should be the quantity of tuberculin used as a subcutaneous inoculation for the production of a constitu- tional reaction to establish the diagnosis. If that amount prove insufficient by producing a negative result, the test should be repeated in forty-eight hours and five times the quantity of tuberculin used the first time should now be inoculated ; that is, 0.50 c.c. of the fourth dilution. Should this fail, 0.10 c.c. of the third dilution should be used in forty-eight hours, and if that should be negative, 0.50 c.c. of The inoculation ^he {hi rc [ dilution used is as a fourth inoculation. As a final should be repeated every test, 0.10 c.c. of the second dilution should be given forty- s ubs r e s qu ent ry eight hours later, the last dose being the one recommended dose should usually as the quantity to be used for the test. If, as it very greater until frequently occurs, there is a reaction from the first dose, the o^io c.c. of the temperature rise during such a reaction will not be very 2d dilution is A > reached and marked, with the constitutional symptoms even less marked. produces no But how would such an individual fare with the last dose ttstTs 011 ^ tuberculin which is one-hundred times the quantity? negative. Even were the patient to react to the fourth test for the first time, this would be brought about by only one-fifth of the quantity usually recommended, and to inoculate five times the quantity that would suffice to produce ,a reaction, is. suffi- cient to cause a dangerously severe reaction. Again, it may be argued that where more than one inocu- lation is made for the production of a reaction, the tolerance gained from the first inoculation may prevent a reaction from the subsequent ones and thus exclude the diagnosis of tuber- THE TUBERCULIN REACTION IN DIAGNOSIS 23 culosis where it might exist with a low degree of hypersuscep- tibility. Such an occurrence is prevented by making the reinoculations at no greater interval than forty-eight hours. Tuberculin, when given in such increases as recom- mended for the test, when repeated in forty-eight hours, rather tends to superimpose the effect of one dose upon the The serial . -, f i .... . test thus other than to gain any tolerance lor the patient, for its action becomes a does not stop in fortv-eight hours. On the other hand, with easure of individual this method of producing a constitutional reaction for diag- hypersus- nosis, we hardly jeopardize the good effects that might be obtained with tuberculin treatment in the event of a positive diagnosis. Another great advantage that may be derived from such a method of eliciting a constitutional reaction for diagnostic purposes is that this method becomes more or less a measure for the individual hypersusceptibility present, so that if the patient does not react to the first three doses but does to the fourth, we could begin treatment in this case with the third dilution instead of with the fifth and so save a considerable period of time both in arriving at the maxi- mum amount of tolerance and in the total length of time required for the treatment. Tables of Dosage for Subcutaneous Tests Pulmonary OT Dilution No. 4 0.10 c.c. " No. 4 0.50 c.c. " " No. 3 0.10 c.c. " " No. 3 0.50 c.c. " " No. 2 0.10 c.c. Bone and Joint Tuberculosis and Uro-Genital Tuberculosis OT Dilution No. 3 0.10 c.c. " " No. 3 0.50 c.c. " " No. 2 0.10 c.c. TUBERCULIN AND VACCINE Glandular Tuberculosis and Lupus OT Dilution No. 2 0.10 c.c. " " No. 2 0.50 c.c. " " No. 1 0.10 c.c. The principal contra-indica- tion of the tuberculin test is the possibility of a diagnosis by other means. Heart disease is no contra- indication to the milder reaction pro- duced by the above procedure. Nephritis is a contra- indication. Centra-indications There are no contra-indications to the local tuberculin tests, except those mentioned in connection with the con- junctival test. There is, however, an ever present contra- indication to the use of constitutional reaction for diagnosis and that is the possibility of making a diagnosis by any other means. It is far better to begin the treatment of doubtful cases and form the conclusion later that the case is not tuber- cular from the failure of obtaining a reaction during a treat- ment, than to produce a severe constitutional reaction in a case that is tubercular. Other contra-indications are as follows : Heart disease. Owing to the disturbances in the circula- tion produced by very severe reactions in isolated instances, heart disease was deemed by some authorities to be a contra- indication to the tuberculin test. This is, however, true only of the very severest forms of heart disease, such as myocarditis or fatty heart and very severe valvular diseases, in which conditions it makes ivery little difference in practice whether we know that the patient has tuberculosis or not; so these need not be discussed here. The milder reaction obtained by the divisional injection of tuberculin as sug- gested above will produce no harm whatsoever in the ordi- nary form of heart disease. Nephritis. Nephritis, we must consider as contra-indi- cating the subcutaneous test. It is well known that any febrile reaction produces albumen in an individual with healthy kidneys and it is therefore far better to treat a case with tuberculin, although the diagnosis is doubtful, than to run the risk of causing permanent damage to the kidneys, which are already the seat of nephritis, in order THE TUBERCULIN REACTION IN DIAGNOSIS 25 to be sure of diagnosis before treatment. It is well to state right here that a routine urine examination should be made before every subcutaneous test. Intestinal ulceration-s. During convalescence from acute The suspicion , - . , . ... of tuberculosis disease such as typhoid, pneumonia, peritonitis, acute ap- inanuicera- pendicitis and gastric ulcer, where a tubercular basis to twe infectlous process in the these ulcerations may be suspected, a constitutional reac- alimentary canal contra- tion may lead to too great a focal reaction or hyperemia, indicates the -,. . . .L i j? TIT constitutional rendering an increasing peristalsis from any cause liable to test set up a fatal hemorrhage. Treatment under such circum- stances is not inconvenient for the patient, for the suspicion of tuberculosis presupposes too slow or poor convalescence, thus requiring visits from the physician anyway. Contagious or infectious diseases preceding less than Theconstitu- . i > i ^ tional reaction six months a condition requiring the constitutional reaction ; s apt to be for diagnosis, absolutely ( contra-indicate a subcutaneous to se *' soon after con- tuberculin test, for a hypersusceptibilitv following conta- ^e'^us dis- eases even by gious diseases in children or any acute infection whether in the divisional child or an adult is so marked, that even a carefully applied test may call forth a very severe reaction. General miliary tuberculosis. The subcutaneous tuber- General miiiar culiii test is contra-indicated where general miliary tuber- is SUSpected. are absolute contra- Epilepsy. The subcutaneous tuberculin test in epilepsy indications. is contra-indicated no matter how long the patient has been free from a seizure in the latter trouble. Fever. The presence of fever is another contra-indication The presence to the test; as a patient suffering from fever more or less indicates th distorts the mechanism of the tuberculin reaction, a foreign subcutaneous injection during fever may merely cause a higher rise. If a patient with a temperature is suspected of tuberculosis, treatment of that patient should be commenced with tuber- culin. because as said elsewhere, if the temperature is caused by a tubercular process, tuberculin treatment will soon act as an antipyretic and reduce that temperature. The tuber- TUBERCULIN AA~D VACCINE Hemopytsis is so constant an indication of pulmonary tuberculosis that no test is required. culin treatment in this instance could do no harm, should the patient turn out to be non-tubercular. If, however, the patient is tubercular, then no time has been lost in applying the tuberculin treatment. Hemoptysis. Recent hemoptysis in case of suspected lung tuberculosis is a centra-indication to the subcutaneous tuber- culin test. The same condition holding true in case of fever holds true in a case following recent hemoptysis. Careful treatment with tuberculin is indicated, and is of great importance to the patients, as all these individuals can be classed under the very beginning stages where tuberculin has its maximum effect A lung lesion with physical signs- so few as to make the diagnosis doubtful, together with the fact that so few conditions other than tuberculosis produce hemoptysis, makes the treatment for these conditions with tuberculin absolutely justifiable. It goes without saying that before beginning treatment of such an individual, the physician must make sure that the bleeding was not from the gums pr other chronic conditions in the larynx, pharynx, naso-pharynx and nasal passages. A second application of the cutaneous tests is advis- able in order to verify a negative finding. Determination of the Tuberculin Test The local tuberculin test merely determines the presence of hypersusceptibility. It also determines the presence of a previous lesion, except where the individual tested is too- young to have had a previous lesion. The negative results,, however, are sufficient to exclude the presence of a tuber- cular lesion, taking it for granted that the tests were pro- perly carried out. In order to be certain, it is advisable in all such instances fa repeat the test for the verification of the negative finding. In the case of the subcutaneous test, the determination of the positive finding will rest with the presence of a well defined focal reaction. The following two reports are but examples of many such investigations with no less striking findings made in THE TUBERCULIN REACTION IN DIAGNOSIS 27 various parts of the world, showing the absolute specificity of tuberculin to the presence of hypersusceptibility and tubercular infection. Incidentally, they emphasize the fact that the constitutional reaction is absolutely safe and is not capable of rendering a closed or healed lesion active, in spite of the assertion of the antagonists of tuberculin that the reaction renders the tubercle bacilli " motile, causing reawakening of the process, spreading the disease beyond its original focus." One report is that of Binswanger (Arch. f. Kinderheilk, 1906, Bd. xl, Heft 1-4). Of 261 children whom he injected, 35 reacted. Of these 261 children thus tested, 42 came sub- sequently to post-mortem examinations, the children having Report of died from various causes. Of these, 16 had reacted posi- 1 tively during the tests and were now all found to be tuber- cular. Of the remaining 26 who failed to react, 25 were found to be free from a tubercular lesion, only one having any sign of tuberculosis. Even this one did not prove an exception to the negative finding, as the injection was made in the fifth week of its life, when in all probability infection had already taken place, but !no tubercular lesion had yet time to form until after the test, Through the reactions in various experiments made at army recruiting stations in different parts of Europe, it was found that the subcutaneous tests were positive in from Recruiting- 30 to 60 per cent, of pases. Upon investigation, it was arm ypst& found that the higher per cent, were found among those coming from areas with known widespread tuberculosis, and ' that those soldiers coming from less infected areas, showed the smallest percentage of positive test. The two points to be deduced from these findings are: first, the absolute spe-* cificity of the tests; second, that in healthy individuals the subcutaneous test is of no greater value than the cuta- neous test and the percutaneous test. It merely points to the presence of tubercular infection, which may have existed before and which is cured. One more important point was 28 TUBERCULIN AND determined by these tests as made in great numbers: that at no time has the test in question caused a reawakening of a former lesion, thus emphasizing the findings of a great many authorities, that the subcutaneous test is not harmful to the individual with healed tuberculosis. Hence, we can conclude that the subcutaneous tuberculin test has all the merits of the other tests, plus the great advantage to be gained by measurable doses. The knowledge of the exact quantity absorbed, when figured in relation to the reac- tion produced, has the great additional advantage of help- ing to determine the activity and the extent of the tuber- cular process. Thus, the rapid Reaction to small doses, indi- cates a more active recent disease, whereas slow reaction to repeated increasing doses of tuberculin may point to an older chronic process. The degrees between these two are numer- ous and have to be determined by careful observation of the patient's history and clinical manifestations before and immediately following the test. It is therefore impossible to lay down schematic rules for the determination of a tuber- culin test. Cutaneous Tests The cutaneous test of von Pirquet is the most important and most widely used. The technique is very simple; the flexor surface of the forearm is preferred both on account of the absence of hair and the ease with which the findings can be read. The skin is rubbed with ether and scarifications made about two Technique of inches apart, three in number and no more than about 1/16 test. inch in diameter. The scarifications can be made with an ordinary needle, but great care must be token not to pene- 'trate beyond the epidermis in order not to draw blood. A moment or two after scarification, a slight serous moisture should appear on its surface. The flat end of a toothpick is dipped in pure old tuberculin and rubbed over the two end scarifications, using a separate toothpick for each. A dry toothpick is used in the same manner over the middle scari- THE TUBERCULIN KEACTION IN DIAGNOSIS 29 fication so as to produce the same amount of trauma on all three. The scarifications are deemed insufficient if a tiny scab does not form over each in an hour after the procedure. Bleeding must be avoided in order to prevent absorption of the pure tuberculin; for, however small the quantity, it can still cause a constitutional reaction in a sensitive indi- vidual. We must remember that hypersusceptibility might exist to a .very high degree in early infection even though the infection may be so mild as to escape recognition, re- quiring this test for a diagnosis. One ten-thousandth of a cubic centimeter of old tuberculin would give a violent reac- tion in many early cases of pulmonary tuberculosis, and one ten-thousandth of a cubic centimeter of pure tuberculin is so minute in quantity that a deep scarification would allow of its ready absorption. The middle scarification is the control scarification. Interpretation. The interpretation can usually be made The ful1 ? at the end of forty-eight .hours, when the maximum effect is reaction should developed. However, the result is often well marked in ^e looked for during the twenty-four hours and very rarely takes three, five or eight second twenty- days before full development of the reactions occurs. We have two reactions, the traumatic reaction and the reaction of hypersusceptibility. The traumatic reaction occurs over all three scarifica- tions. It consists of reddening, with a formation of a scab the size of a pinhead, falling off in about twenty-four hours, leaving a pale brown discoloration behind. The reaction to hypersusceptibility or the positive cuta- care should neous reaction has a latent period of about five hours to distinguish a several days, but in most cases it develops after twenty-four mild reaction hours, and reaches its maximum in forty-eight hours. The traumatic reaction consists of an exudate and a hyperemia, making reactlon - itself manifest in a raised reddening, starting from the scari- fication and increasing outward until it reaches a diameter of about 10 mm. If the reaction is very severe, this jnight reach 20 mm. or even 30 mm. in extent, with many small 30 TUBERCULIN AND VACCINE papules forming around the edge of the reaction. Even a bluish-red areola might appear where the reaction is intense. After forty-eight hours the redness begins to fade, passing over into a very faint violet, leaving a slight pigmentation, which may remain visible for a long period, and Anally disappearing with a slight scaling of the skin. Variations. The variations in this reaction are innumer- able, depending in the first place upon the state of hypersus- ceptibility at the time of the test, the stage of the disease, and the general circulation of the patient. Thus an anemic individual will show a paler papule than one with good circulation; and a well nourished individual will have a larger papule with .vesicles better marked than one who is emaciated. In comparing the test scarification with the control scar, one must allow a certain degree of difference even for a negative result, for the tuberculin contains irritating mate- in the positive r1 ^' affecting even the tuberculosis free individual. This fact vonPirquet jj ag ] e( j von Pi r q ue to warn the profession against consid- vary.but all are diagnostic, ering a local papule less than 6 mm. in diameter, as a reaction, even though it looked more inflamed than the con- trol scar. In case of doubt, it is advisable to start a new test on the other arm after forty-eight hours. The second test will be decisive ; for it is an established fact, that even the local inoculation of tuberculin will increase the hyper- sensitiveness of a tuberculous individual, and will render the second test more pronounced than the first test. In doubt- ful first tests, the slight increase in the severity of the second test will be sufficient to decide the question. The increase in the second reaction is far more diagnostic than the ordi- nary test, for it shows a universal sensitization of the organ- ism with the first test; and it has been frequently shown that tuberculin cannot sensitize an organism perfectly free from tuberculosis. Negative finding. The negative finding of the cutaneous THE TUBERCULIN REACTION IN DIAGNOSIS 31 test, especially of the second test, speaks absolutely for the absence of tuberculosis in any form. The following T h _?. ne s ati 3 finding is of exceptions should be noted : After tuberculin immunity f ol- the utmost lowing specific treatment in individuals suffering from gen- value in the ral cachexia, and in peculiar skin conditions. In those tubercular cases, where in spite of demonstrable tubercular processes inf ction. this reaction is negative, there are either spent tubercle bacilli, as in fungoid fistulae, or suppurating local conditions, or else the organism has lost its reactive power. This last condition von Pirquet explains as being caused by the absorption of the ergins (the bodies which cause the reaction between the tuberculin and the cells) preventing tubercular allergin, which is responsible for the rapid spread of the disease in those individuals. This phenomenon is explained by von Pirquet in connection with negative results obtained in children suffering with the measles or during the incu- bation period of scarlet fever. This explanation fits well with the often noticeably rapid spread of an otherwise mild tubercular process, following measles, scarlet fever and other infectious diseases; also during pregnancy. Since these negative findings are based upon the loss of the immune response they occur only in cases of evident tuberculosis and do not lessen the value of the tuberculin test in those cases where the establishment of a diagnosis by the tuberculin test is necessary. Positive findings. The positive findings in cutaneous tuberculin tests merely point to the fact that tuberculosis exists. It gives no clue as to its location, nor does it prove The positive its clinical existence. This fact should be borne in mind, diagnostic value especially when testing adult patients. A positive well l ". v ,'j ry young marked reaction should put us on our guard and a thorough search should be made for a tubercular focus. A subcu- taneous test to bring about a constitutional reaction seems best indicated under these conditions. The focal manifes- tations during a constitutional reaction will aid greatly in the localization of an active process. (See page 40.) the Moro test. 32 TUBERCULIN AND VACCINE In children up to the fourteenth year, the diagnostic indications of the cutaneous tuberculin test is at the highest degree. In von Pirquet's clinic, where thousands of chil- dren have been tested, 97% of tubercular children gave posi- tive reaction or showed naked eye evidence of tuberculosis at autopsy. No case which ever gave a negative result showed any gross or miscroscopic signs of tuberculosis. Escherich's Needle Tract Reaction This reaction is practically a local reaction, such as we get in subcutaneous tests. The recommendation is to use 0.20 c.c. of No. 3 dilution in the subcutaneous tissue on the flexor side of the forearm. If the reaction is positive, a red spot appears sharply circumscribed and quite distinct from the red areola that forms around the needle puncture. This begins in about six hours and comes to its height in about forty-eight hours, after which it begins slowly to dis- appear. Infiltration, edema and great tenderness accom- panies this reaction as a rule. When no general reaction occurs and this local reaction is indistinct, the dose may be doubled. Elc5c U h e -s f The indi cations for this test, as well as its positive find- ings, are the same as for the von Pirquet. Its disadvantage lies in its much greater liability to produce a constitutional reaction. It therefore should not be given preference over the von Pirquet It should be used only after a doubtful von Pirquet for confirmatory purposes where the technique of the von Pirquet was uncertain and a surer entrance of the tuberculin into the skin is required. Percutaneous Tuberculin Test of Moro Moro used inunctions of equal parts of Koch's old tuber- j . , -. j . , ilm and anhydrous lanolin. He recommends as the site for the inunction, the abdominal wall beneath the ensiform car- tilage, or the skin of the chest above the nipple; but considers the use of the forearm as unsuitable for this test. A quan- THE TUBERCULIN REACTION IN DIAGNOSIS 33 tity of the ointment, about the size of a pea, is rubbed for about a minute with the index finger over an area of 5 c.m. in diameter using moderate pressure. A protection for the finger is unnecessary, as the surface of the hand or finger does not react to tuberculin. The inunction area should be exposed to the air for a few minutes and no further atten- tion paid to it. Dressing is unnecessary. The reaction ap- pears both as to time and grades of intensity, in the same manner as with the cutaneous test of von Pirquet. From the mass of literature on the subject, there can be no further doubt that the positive reaction is absolutely specific. There is no contra-indication to this test, except in pro- nouncedly scrofulous children. Here a distant cutaneous reaction might occur, causing great discomfort from itching and occasionally seriously affecting for the worse the scrofu- lous process. It shows a great many less positive reactions in known positive cases than the von Pirquet test and has Except in ,.-.. .-i f , f , mi isolated not the advantage 01 limited area for its manifestation, ihe instances this only instance where it might be advantageouslv used in test . IS mferior * "to the von preference to the von Pirquet, is in a case where the physi- cian does not wish to disclose to the patient the nature of his test, or the fact that he is testing at all. For instance, there are mothers who fear an inoculation of the disease, when the inoculation method is used, leaving the Moro test as the only choice. The modifications of the Moro test, such as Lignieres' and Lautier's are much inferior to the original Moro and cannot be recommended. Intracutaneous Tuberculin Test The intracutaneous tuberculin test consists of the injec- Technicof ,, TS ^ i . .-i the intra- tion oi a quantity ol tuberculin into the skin, and under no cutaneous test circumstances should the injection be deep enough to make it hypodermic. The place chosen should be the thigh, arm or inner side of the forearm. A fold of skin is raised, the needle puncture is made flat in the skin and is pushed paral- lel with the fold for a very short distance. Solution No. 3 3 TUBERCULIN AND VACCINE The positive reaction develops during the second 24 hrs. reaching its maximum in 48 hrs. The danger of a constitutional reaction and the great discomfort it often produces, render it inferior to the von Pirquet. of old tuberculin is used and such quantity injected as will raise a white wheal about % to 3/16 of an inch in diameter. The white wheal disappears in about 20 minutes, and noth- ing remains visible except perhaps the needle puncture, until the positive reaction sets in, which is in about five to six hours, reaching its maximum within forty-eight hours. Commencing with a slight infiltration, appreciable only to touch, the infiltration increases until it reaches about an inch in diameter, surrounded by an inflammatory area, which sometimes reaches in extent to the size of the palm of the hand. In the center of the infiltration appears a reddish, sometimes edematous area, with an erythematous edge. The area may be covered with small red papules; or, when the reaction is severe, actual blistering occurs. After forty- eight hours the infiltration begins to subside, inflammatory symptoms begin to diminish and in a few more days the mark disappears nearly entirely with the scaling of the skin. The hard infiltration may, however, persist for weeks. If the test is negative, only a very slight indur.ation with the faintest brown coloration occurs, disappearing in about two days ; and since positive reaction would reach its height by that time, there is no difficulty in recognizing it, even if very mild. This factor is the favorable feature of the intracutaneous tuberculin test But Angel's claim that it produces no dis- comfort is disputed by a great many authorities who have used this test extensively. My own observation found that the positive reaction produces great discomfort with in- ability to use the arm for several days; also a definite con- stitutional effect has often appeared, including focal reac- tion, such as enlargement of tubercular glands of the neck. The general effect of the intracutaneous test is the same as the cutaneous one, with the added disadvantage of greater intensity of its action. However, it can be used with advantage, where the cutaneous test is negative, on account of the control of the quantity of tuberculin used in THE TUBERCULIN REACTION IN DIAGNOSIS 35 the test; thus, Angel recommends the use of 1 :5000 dilution first, 1:1000, 1:100 and finally 1:10. This test is also of value where the subcutaneous test is contra-indicated and the cutaneous test has proved negative. However, the sphere of this test cannot be extended beyond that of the cutaneous test, and seems to be limited to early childhood, rendering its fields of usefulness extremely small. Conjunctival Tuberculin Test This test was discovered by Calmette and Wolff-Eisner, as a modification of the von Pirquet test, and was reported under the names of " ophthalmic reactions " and " conjunc- tival reactions." The latter name is more appropriate, as Technicof *'. * the conjunctiva! the reaction occurs in the conjunctiva only. Special tuber- test, culms were at first deemed necessary ; but according to Ban- del ier and Roepke and others, the original Koch's old tuber- culin is the best. It obviates the difficulty of obtaining the special kind and is a great deal less expensive (95% alcohol precipitate of tuberculin dried and sold in small ampules, a watery solution to be made at the time of use). The tech- nique is very simple. An ordinary dropper can be used, a single drop of one to four per cent, of old tuberculin in adults, and a half to one per cent, in children. The drop is placed in the conjunctival sack, care being taken that the end of the dropper does not touch the sack and cause a flow of tears, or movements of the lids that may expel the tuberculin. The tuberculin is now kept a minute or two in the closed eye and no further attention necessary; no bandage or eye pro- tection is required. The reaction begins in from five to six hours and usually comes to its height in about twenty-four hours, remaining visible for several days afterwards. The reaction grades from a reddening of the conjunctiva, which can only be seen on everting the lid and comparing it with the other side, to a reddening of the entire conjunctiva visible from a distance. In severe cases, swelling, much fibrinous or purulent secre- 36 TUBERCULIN AND VACCINE This test should not be used as even its negative finding; has no diagnostic value. It is also dangerous to the eye. Hypersus- ceptibility may remain in the con- junctiva after tion, and even echymosis may appear. -These tests may be repeated two, three and four times and it is advisable to begin with a much weaker solution than is usually used in order to avoid the severer form of the conjunctival reaction in hypersensitive individuals. Begin with the \% solution and increase to 2, 3 pnd 4% in the subsequent tests. It is also advisable to use each eye alternately, as the severe forms of reaction occur in patients where an overlooked posi- tive reaction in a conjunctiva has increased the hypersensi- tiveness of that conjunctiva and caused the reaction from the second installation to be very severe. The specificity of the test is beyond doubt as true of the conjunctival test, as it is of the cutaneous or intracutaneous test. However, this test cannot be recommended, for not only is it often dangerous, causing severe damage to the eye, but its negative finding is not reliable, as over fifty per cent, of early active tuberculosis have shown negative reactions in the hands of many investigators. Special warning should be taken against the use of tuberculin in a conjunctiva that has been the seat of a positive reaction, no matter what length of time intervened. This warning also applies to the use of a conjunctival test following a cutaneous or subcutaneous test, before the hypersus- ceptibility awakened by these tests has entirely subsided. Under no circumstances should a cutaneous or subcutaneous test be made before a conjunctival test has entirely subsided, as the increased susceptibility produced by the cutaneous and subcutaneous tests might reawaken the conjunctival reaction and cause a very severe reaction in the conjunctiva. It can thus be seen how a positive conjunctival test may interfere with the necessary therapeutic tuberculin inocu- lations. Once the conjunctiva has been rendered sensitive, it may severely jeact after each dose of tuberculin even though the quantity may not be sufficient to cause a constitu- tional reaction. I have now under my care a little girl nine THE TUBERCULIN KEACTION IN DIAGNOSIS 37 years of age, who has been treated for tubercular adenitis for test causing recurrence of conjunctivitis over a year without marked success. A conjunctival test r was made in order to determine the nature of the glandular after every tuberculin involvement and proving positive was sent to me for tuber- inoculation culin treatment. At present I have the greatest difficulty for treatment - in gauging the ; dose of tuberculin, as the slightest approach to maximum tolerance causes a severe conjunctivitis. Above all, we must take special heed that every, possible eye disease be excluded before a conjunctival test is undertaken. Subcutaneous Tuberculin Test As in the case of a local test, the subcutaneous test is also a specific reaction to hypersensitiveness on the part of the individual, the difference being in the degree, as a constitutional reaction also takes place, due to the absorp- tion of the tuberculin in this method of administration. As a direct result of the tuberculin inoculation, as given in Several this form of the test, we get a focal reaction at the point of^hepatien* of the disease, which phenomenon reveals the place of in- ar e necessary before the test, fection and to a greater or lesser degree the activity of the in order to , , , . . , , . , recognize the process. Care must be taken to distinguish this reaction by f oc ai reaction, becoming thoroughly acquainted with the condition previous to the injection. It is safe in the hands of the practitioner, provided the divisional method of administration is resorted to, as herein described, so as not to produce too violent a reaction with an active lesion. A description of a detailed technique for a subcutaneous inoculation would seem superfluous as every physician has had experience with the hypodermic syringe. Still, when we consider for a moment that an individual will have to Techmcof the sub- submit to a large number of inoculations, anything that the cutaneous , . . , ... i . tuberculin physician can do to eliminate pain at the time 01 inoculation test . or prevent severity of a local reaction that may be brought about by a greater traumatic reaction, will be desirable. In this connection two important points are worthy of 38 TUBERCULIN AND VACCINE mention. First, have the arm where the inoculation is given in such p. position that the needle easily penetrates the skin, and the physician , is able to tell that the point of the needle is in the subcutaneous .tissue. Sec- ond, the tuberculin should not enter intracutaneously, thereby avoiding an undue amount of traumatic reaction. Both these objects can be accomplished by rendering tense the skin through which the needle must penetrate. It will then (feel las if the needle penetrates a membrane entering a vacant space beyond which is the subcutaneous tissue. The best way to render the skin tense is by grasping the arm from behind, drawing all the tissues backwards, as shown in the illustration. (Fig. 6.) This will be found to be an improvement over the usual method of pinching up the skin when giving a hypodermic injection. Pressing the tissues together makes it impossible, at times, to tell whether the needle has penetrated into the muscular layer. It is also advisable to bear in mind that the finest, gauged needles can be used and that the points must at all times be sharp especially where there is a (tendency to leak- age from the puncture in the skin. Such an occurrence may sufficiently vary the amount of tuberculin absorbed to produce a sudden severe constitutional reaction during the treatment. The loss of tuberculin from such oozing may be very small in amount or, it may even amount to the entire dose given. It is therefore necessary to guard against such an occurrence by placing the cotton tipped applicator (or toothpick) dipped in iodine, over the point of puncture immediately upon withdrawing the needle. The same appli- cator that was used in painting the small area of skin with iodine, preparatory to inoculation may be used. It need not be dipped again in the iodine before this procedure, as a second application of iodine to the same spot may cause local irritation on a tender skin, especially if the iodine happens FIG. 6. THE SUBCUTANEOUS TUBERCULIN TEST. The skin is rendered tense by drawing the tissues towards the back of the arm with the left hand, while plunging the needle with the right hand through the center of the area painted with iodine. THE TUBERCULIN REACTION IN DIAGNOSIS 39 to be old. (Fig. 7.) The applicator is held there for a moment or two, using a little pressure, a drop of collodion being placed over the needle puncture after withdrawal of the applicator. Massage after a tuberculin inoculation should never be resorted to, as it is desirable to have the absorption of the tuberculin take place as slowly as possible from the point of inoculation. In the event reinoculation is necessary, it should be made at a considerable distance from the former inocula- tion, as a local reaction may take place in the tissues that have been somewhat sensitized from a previous inoculation, where such a reaction would not have taken place otherwise. The result of this would be a false finding. It is better still to use each arm alternately for repeated inoculations. SYMPTOMS OF THE TUBERCULIN REACTION The principal elements in the general reaction elicited from a subcutaneous injection consists of the three principal elements : local reaction, the constitutional or febrile and the focal or lesion reaction. Local reaction. The most frequent symptom of a general A hardened ..... m1 . nodular reaction is the reaction at the point 01 injection. Ihis con- induration at sists of a painful swelling at the site of the injection, with the inoculation an infiltration of the subcutaneous tissue to various degrees constitutes around it. So frequent is the occurrence of a local reaction reac tion. in a general reaction, that its non-occurrence usually throws doubt upon the interpretation of the rise in temperature as a general reaction. One must, however, be careful in the search for a local reaction, for it sometimes occurs in the subcutaneous tissue without producing superficial redness, and only careful feeling over the point of injection will reveal the small subcutaneous indurated mass. (Fig. 8.) Constitutional reaction. With the constitutional mani- festation of this reaction, we have a disturbance of the gen- eral health, by symptoms pf varying degrees. The severe forms begin with a rigor, followed by sensation of heat or 40 TUBERCULIN AND VACCINE The constitu- by a cn ill with an intense headache, accompanied by malaise, tional reaction . . .., . . . j? 11 1 resembles in dizziness, nausea and even vomiting. Ihis is soon iollowed influeT.the' by pains in the limbs, dragging or a sensation of pressure in symptoms tne affected part, accompanied by loss of appetite, thirst, disappearing in a surprisingly palpitation and sleeplessness. All these symptoms dis- appear with a fall }in temperature, leaving a feeling of weak- ness lasting a day or two. All these symptoms Jast a sur- prisingly short time, considering their severity and nearly all symptoms disappear within forty-eight hours. The vari- ability in the constitutional symptoms is great and depends entirely upon the individual constitution. Thus, we may The constitu- have a very high rise in temperature, to 103 or 104, without the least subjective manifestation, or we may have a tem- reactionusu- perature rise of only one degree with the severest subjective during the symptoms. When carefully conducted, there should be no appearance of extreme constitutional symptoms and the tem- t'on- perature should never rise above two degrees. The usual appearance of a reaction takes place during the second twelve hours following the inoculation. However, it sometimes ap- pears as early as four or five hours ( after inoculation and occasionally does not appear before thirty to thirty-six hours after inoculation. The focal Faced reaction. The focal reaction is the distinguishing is the feature of the subcutaneous tuberculin test. It not only determines the presence of active tuberculosis and its extent, teaturc ot * the test. but very often helps to determine the location of the tuber- cular processes, which remained undiscovered. For instance, tenderness, which did not exist before will appear over a beginning affection of the spine during the tuberculin reaction; tenderness over the sternum with a feeling of pressure in the chest will reveal as a result of focal reaction, tubercular thoracic glands, on account of their swelling. A focal reaction is a transitory increase of the inflammatory process in ,the tubercular area and its manifestation will bring out the symptoms which go with an inflammation of the particular organ which it affects. FIG. 7. THE SUBCUTANEOUS TUBERCULIN TEST. The needle is not with- drawn until the applicator with cotton on the end is placed over the injected area, ready for the pressure to be put over the puncture on withdrawal of the needle, to prevent loss of tuberculin through oozing. FIG. 8. THE SUBCUTANEOUS TUBERCTJLIX TEST. The local reaction as it appears in the majority of instances and designated on the Treat- ment Charts as moderate. THE TUBEBCULIN REACTION IN DIAGNOSIS 41 Treatment of constitutional reaction. Regarding treat- Treatment of . . thecon- ment of the reaction, only a few words are necessary. For stitutionai the severe forms, rest in bed, with perhaps one or two doses sympto of the coal tar products for severe headache, is all that is necessary. I warn particularly against the use of anti- pyretics, as we want the highest point of temperature revealed. In less severe forms, there is no necessity of keeping the patient in bed, avoiding manual labor or tiring exercise is sufficient. CHAPTER I EQUIPMENT Although it has been my aim in writing this book tq simplify the treatment of tuberculosis to the greatest possible degree, there are certain details so essential to the success of the treatment, that one has to familiarize himself with them at once and give them his closest attention. I have endeavored to set these down under a separate chapter before going into the matter of the treatment of the various forms of tubercular affections in order to show at a glance all that is necessary to begin with. I have come to the conclusion that it is not sufficient to merely make mention of these various items dispersed throughout a work of this kind, as in this way important details will very often be overlooked and so lead to much embarrassment and to complete abandonment of this impor- tant treatment. Again, the amount of detail will be seen to be far less burdensome if put down and explained at the outset, than if it has to grow upon the reader during the theoretical and practical discussions of the various phases in the treatment In fact, after a careful perusal of this chapter, it will be noticed how simple after all, the arma- mentarium of the practical immunizator need be. The simplest As regards the more elaborate paraphernalia described equipment . -i-ii .-,.. possible is in other works these were suggested with the specialist in ThtncetMtty m * n< * an< * were P rom P te( l D 7 & desire for completeness of for more their discussion. One may take advantage of these susr- elaborate , . J p equipment gestions alter the treatment of several patients when the we win leave w hole subject will no longer be new and the mysteries sur- tor experience to discover. rounding it will have vanished. These suggestions represent the refinements that come with experience, rather than the EQUIPMENT 43 actual requirements of the condition. And since they only help to complicate the subject from the beginner's point of view I thought it wiser not to touch upon the more com- plicated equipment in this work. Proper Record Sheets or Cards No one should attempt to use tuberculin or vaccine with- out keeping a careful record of the amount and date of each dose with the results following each dose ; the weight of the patient and a record of various other data, such as laboratory findings, X-ray findings and other data during treatment of the patient. A chart in the form of a folder (thus having four Pr p r records are pages) can have the history and diagnosis on the first page, essential. The second page can be properly ruled for the record of the tuberculin administrations. This page should be ruled in eight parallel columns, the first for the date, the second for the number of the inoculation, the third for the number of the dilution used, the fourth for the quantity of tuberculin inocu- lated, represented by the amount of the particular dilution ; two columns for reactions, one for the local and the other for the temperature; the seventh column for the weight record and the eighth for miscellaneous remarks. (See Fig. 9, page 45.) The sheet may be large enough to accommodate a double series like this on the one side of the folder, and will thus have room for 100 treatments, which is more than sufficient in most instances. Page three is divided into two parts, one-half for additional notes and the other half as a record for other medication. Page four can be used for the record of vaccines for mixed infections. Within the folder can be kept various laboratory reports, X-ray photographs and temperature charts. The whole sheet is made of heavy paper and measures 15 1/2 inches in length and 8 inches in width and is so folded that the right hand sheet is one-half inch wider than the left, allowing the half inch to be visible for the name and diagnosis, and for filing purposes. During treatment it may be filed under 44 TUBEBCULIN AND VACCINE the name ,of the pa.tient and after the treatment, it may be compiled under the form of the disease. It is difficult to conceive how any physician would fail to keep the proper records when treating a condition with tuber- culin, for every dose is figured from the preceding doses under any form of tuberculin administration. Even were he able to remember all the quantities injected over a period of months, it is reasonable to suppose that no one would prefer burdening his memory, to the simple procedure of writing down a quantity ; still, the following is an example : The patient, a little girl, eight years old, with a tubercular knee joint The physician commenced treatment of this child with tuberculin after a single visit to my clinic at the Xew York Polyclinic Hospital. After five months' treat- ment, the physician died. The father of the child wrote to me asking whether I would continue the treatment of his little girl. My answer was in the affirmative and I requested that he bring a record of all the treatments the child had received up to that time. The following is a transcript of the letter that he brought to me, written by the former assist- ant, and successor to the physician: I Dear Mr. L. Here is a record for A., as per your request. Do not remember how many times we omitted the injection of the tuberculin, as we did not make a record of it only the calls. Feb. 2 Mar. 6-23-27 Apr. 5-7-12-15-21-25 May 2-6-10-13-16-20-24-27 Jun. 3-8-13-19-23 Hoping this will be satisfactory, I am, Yours very truly, Dr. X. It is needless to state that the child had not improved in that time and the father expressed great disappointment over the fact, as he was led to believe that the child would EQUIPMENT 45 J & i 3 \ \ . * a> bo | g & .s J O5 d r r" ^ ^ * r ^ > i i 1 & ^ HISTORY DIAGNOSIS REMARKS FIG. 10 TubercuUn record page of the record folder used by the author. "So d e | w 2" *S J I- S" 3 IS 6 r-c fv in if V ir rj \t ' If ) If CO f in in o 6 m in c 4J (S Q REMARKS *j bo d II 6 1] i <^ u IS 6 Z Mco^mot^ooo>o : r+ V d tS 46 TUBERCULIN AND VACCINE be cured in from six to eight months. It might also be men- tioned here that no temperature record of the child had ever been kept during the treatment; and the father expressed surprise when he was ' instructed to keep such a record and told that we could not treat the child without the temperature being taken after each inoculation. Syringe The use of the proper syringe will obviate the necessity for a study of the metric system in case one is noti familiar in it. I have found in my teaching that quantities measured in any other way than minims and drams were meaningless. The everlasting question when a quantity of tuberculin is mentioned in the lecture is : " How many minims is that ? " But the minim measurement is out of the question in the administration of tuberculin, as we cannot give parts of minims and one minim is equivalent to approximately 0.06 c.c., which is three times the amount of increase advised at the beginning of treatment. The further diluting of each dilution to make a minim equivalent to 0.02 c.c. will complicate the subject a great deal; whereas, with little trouble, one can obtain the proper syringe. The Record tuberculin syringe is the best for general use. It holds one cubic centimeter, which is divided into ten large divisions. Each large division, which holds a tenth of a cubic centi- meter, is subdivided into fifths, each small division there- fore holds one-fiftieth or 0.02 c.c. Whether one understands the metric system or not, one merely measures the dose by drawing into the syringe the amount desired, the reading of that quantity is on the barrel of the syringe. All glass syringes that are made in this country are even more finely subdivided, each division holding 0.01 c.c. Difficulties are sometimes experienced with these syringes, owing to the slip- ping of the piston in the barrel. This has to be guarded against by pressure with bne finger on the piston where it en- ters the barrel. Rome of these syringes are now provided with a metal spring for that purpose, (See Fig. 1, page 14.) EQUIPMENT 47 Needles Since tuberculin is not very viscid, the finest gauged The needles needles should be used. This is important, on account of the large number of inoculations necessary during treat- ,..,.,, . f order to avoid ment, making it desirable to avoid as much discomfort as traumatic possible to the patient and to prevent traumatic reactions. reactlon - A platinum-irridium needle may be used, as its advan- tage over the plain needle is that it can be sterilized in the flame. But where an all glass syringe is used, a crack- ing off of the screw end or slip end of the syringe very often occurs. The plain 25-gauge needles one inch long, are inexpensive, can be readily obtained and serve the pur- pose as well as any other needles made. The syringe and needles are sterilized in alcohol and rinsed with the diluting fluid before treatment. Office Scales All office balance scales will do for weighing the patients, office scales A physician should not depend upon his patients' weighing outside and bringing in their weight for record. It is sel- dom that a patient will take the trouble to remember the difference in clothes between each weighing ; whereas, in the office one can weigh the patient right after the inoculation. One can always follow a given routine in the office for weighing patients in order to have any extraneous influences eliminated. Containers for Dilutions. (Figs. 3 and 4.) Any bottles holding a little over a cubic centimeter are suitable. If the bottles are so large as to prevent the needle from reaching the bottom, the mouth of the bottle must be large enough to admit .the circumference of the syringe. These bottles may be sterilized by allowing them to remain over night, filled with 95 per cent, alcohol. This alcohol must be rinsed out with diluting fluid before mak- ing dilutions. Small squares of adhesive plaster may be 48 TUBERCULIN AND VACCINE Aside from instructions as to taking of temperature, it is best to limit the first consultations to the diag- nosis of the disease. At the sub- sequent visit, all instructions as to hygiene, diet, etc., should be given. used in labeling the bottles. A cool, dark place for the storage of the tuberculin and vaccines completes the equip- ment. Instructions to Patients Aside from the usual instructions as to hygiene, diet and fresh air, details into which we need not go here, the patient should be instructed in the regular taking of temperature four times daily: at eight, at twelve, at four and at eight o'clock, for at least three or four days, and should be taught to keep a pareful record of it. No other instructions that refer to tuberculin treatment need be given at the (first consultation. The patient's mind is diverted entirely to the realization of his condition; and any other discourse or instruction will lose its force if given at the same time with the diagnosis. However, the carry- ing out of the instructions for taking temperature will pre- vent in a measure the brooding and worry, and will add to his confidence in the physician. At the second visit, the patient should be told the mean- ing of immuno-therapy ; he should be told that tuberculin administered twice weekly will stimulate his own protective processes, helping him in that way to overcome his disease. The prejudices existing against tuberculin must be men- tioned to the patient, so that if they have not reached his ears before, his confidence in tuberculin during treatment should not be lessened by what he may hear from outside sources. It must also be explained that these prejudices were brought about by the faulty administration of tuber- culin, and that with a more careful technique, tuberculin is devoid of danger. It must be especially emphasized to the patient that the treatment must be brought to a conclusion when once it is begun, as an interruption of the treatment before maximum tolerance is reached will often lead to a rapid retrogression of the condition. This retrogression fol- lowing upon a too early discontinuation of treatment has often been laid to the tuberculin itself. Indirectly, it may EQUIPMENT 49 be true; for, just as the sudden discontinuation of stimu- lants in heart disease may sometimes cause a sudden col- lapse of the heart muscle ; so also in tuberculosis, when the healing process depends upon outside stimulation, which when prematurely discontinued will cause sudden retro- gression. We must therefore continue the treatment with tuberculin to the point of maximum tolerance and then for a period of time, determine at regular intervals whether the maximum tolerance is being maintained. (See Tri-Monthly Tests, page 147.) The patient must also be made to understand that the The patient i ' ' ft i- -i it must be a proper administration 01 tuberculin depends a great deal wining upon his own assistance: that he is a "partner" in the P artnermthe treatment to treatment, and therefore must take his temperature regu- insure its larly every two hours, on the day of the inoculation and the day following it. He must note as far as possible any focal manifestation and mention it to the physician when he next presents himself for treatment. The focal manifestations must be explained as an increase in the various signs and subjective symptoms, and the patient must note how long this increase persists after the inoculation, so that we may be able to differentiate between an actual focal reaction and a retrogression in the disease, due perhaps to insufficient tuberculin. It is by far better to instruct the patient to take rectal temperature, if convenient. However, if that be impracti- cable, and the mouth temperature must be depended upon, the patient should be instructed to make certain that the mercury column in the thermometer is shaken down below 95 before taking the temperature and that he keep it under his tongue for at least five minutes by the clock, even if the thermometer be a " one-minute " thermometer. The physi- cian need not expect to meet with any difficulties in the car- ." e * rying out of his instructions w'ith regards to temperature, patient can If he insist that the treatment will depend upon the proper k ^ a an e c taking of temperature and will absolutelv refuse the treat- accurate " . temperature ment if the patient pleads ignorance in the matter, it is record. 50 TUBERCULIN AND VACCINE surprising what ability will be displayed along this line by the most ignorant patients. It was said, when I first established a clinic, that if my treatment depended upon the taking of temperatures by the patients, the whole project would prove a lailure, for the class of patients who apply for treatment at the New York Polyclinic Hospital consists mainly of the ignorant foreign element. In spite of that assertion, the clinic has grown larger in size and every patient who gets the treatment brings on paper his temperature suc- ceeding his last treatment. It is a matter of comment to see what surprisingly neat temperature records these patients bring. The difficulty, if met with, consists of the inability on the part of the patient to get the focus upon the mercury column in the usual magnifying thermometer. The plain thermometer without the magnifying glass can be obtained through any druggist and will remove the only difficulty in the way of the patients reading the temperatures. In ambulatory cases, I have avoided complicating the treatment from the standpoint of the patient by refraining from the distribution of printed slips, requiring the answer to many questions concerning pulse, respiration, headache, pain in the limbs, pain in the joints, malaise, sleeplessness, fatigue, restlessness, nervousness, indigestion, nausea, vomit- ing, chilliness, rash, enlarged glands, and a host of other questions which are printed on slips and distributed among patients in many clinics. I am quite certain that seventy- five per cent, of the answers are influenced by the con- centration upon the symptoms. It is quite sufficient to ask the patient at the time of his visits whether he has coughed more or less, whether he brought up an increased amount of sputum or whether there was a noticeable decrease; whether the amount of discharge from a sinus is markedly increased as shown by the amount of increase of dressings required and whether this discharge is thinning or becoming thicker ; and in a case of glands, whether they have become more swollen or less swollen, or more painful or less painful, and so on through the different varieties of tuberculosis. CHAPTER II TUBERCULIN TREATMENT The methods of treatment with tuberculin resolve them- selves into three distinct classes: the reactive method, the non-reactive method and the combination of the two. The reactive method is the one that Koch originally used, and has but few remaining adherents at the present day. It consists of giving a dose sufficient to cause reaction, and continuing with the same dose every third or fourth day ; each time producing the same reaction. The sudden col- lapse of tuberculin therapy that marked the first tuberculin era was brought about by this treatment, as disastrous results overtook the largest majority of patients treated by this The three method. The fear that overtakes most physicians at the tuberculin suggestion of tuberculin therapy has been instilled by this *? e m t e :stratioa method of treatment; a fear which the great majority of reactive, the physicians try to mask by condemnation. Why base this nd thl one*' condemnation on ignorance and hearsay, instead of dis- that combine* pelling it by investigation and fair trial ? We must remem- ber that this method of treatment was born of a desire to find a remedy for so important a disease as tuberculosis before the hypersusceptibility existing in this disease was known and the desire for an immunizer was so great that its use was attempted far too generally before its true nature was understood. The disappointment that soon followed was consequently so intense that condemnation of tuber- culin took the place of further study and investigation. Fortunately, there were a few investigators who were quick to recognize the indication of its virtues and who con- tinued the use of tuberculin and evolved the second method of treatment; the non-reactive method. It was quite a natural outcome to revert to minute doses after the larger doses had proved unsuccessful. The minute dose was used in the same way, as the larger dose was used, merely inocu- 52 TUBERCULIN AND VACCINE The minut* lating at three to seven-day intervals, the same minute dose or very slightly increasing it. There are still at the present stimulation fay ^ ose wno report fairly good results with this method, of the hyper- 1111 susceptibility but further investigation has proved that the hypersuscepti- th^reby never bility can only be reduced by increasing doses, that the same attained ^ ose h as no further effect upon the hypersusceptibility after tolerance. one or two inoculations. In fact, experience has shown that when the small dose) is kept up for any length of time, the hypersusceptibility increases; a distinctly harmful effect in such favorable cases where tuberculosis is quiescent and the hypersusceptibility is not very marked. However, this harm is very often overlooked and because of its insidious appear- ance, is laid to the progress of the disease and not to the method used in the tuberculin administration. A method The third method and most generally used at the present whTie better day is the method which consists of small doses increased ban the other according to the amount of hypersusceptibility in each indi- remains vidual case. It is well known that to obtain toxic immunity, weTi'chosen we must begin with the dose less than we require to produce cases - toxicity, this dose being increased in proportion to the ac- quired tolerance of the individual. With that in view, methods of dosage have been devised, which depend upon a mathematical increase of dosage entirely too rapid or too large for the majority of patients the increase in tolerance not keeping pace with the increase in tuberculin. Severe reactions are frequently encountered thus making the choice of patients for tuberculin treatment absolutely neces- sary. Only long experience and expert judgment can bring about a fair amount of accuracy in the choice of the pa- tient, a fact that stands out most prominently against the wider adoption of tuberculin therapy. A closer analysis of the principles involved in the physiological action of tuberculin with a view to simplify- ing tuberculin therapy, brought out the following facts: FIRST: The dose of tuberculin has no effect, if it is less than the maximum amount that can be tolerated without any reaction on the part of the individual. ' TUBERCULIN TREATMENT 53 SECOND: It requires more tuberculin to reach the The . principles amount 01 maximum tolerance at each succeeding dose. involved in the THIED: The subsequent doses, although larger than the physiological first in amount, have no effect if the first dose was less than tuberculin, the maximum amount that could be tolerated by the indi- vidual and if the amount of increase is not enough to bring the total to the maximum amount of tolerance. FOURTH : That any constitutional reaction, however mild, increases the amount of hypersusceptibility and the maximum amount of tolerance thereby decreases, thus re- quiring a diminution of the dose following such a reaction. FIFTH : The only index to the measure of tolerance in every individual is ; a constitutional reaction, hence a con- stitutional reaction is desirable in every case. SIXTH : Since a constitutional reaction lowers the point of tolerance, we must be sure to make such a reaction as mild as possible in order not to lower the tolerance to too great a degree. An early experience in otherwise hopeless cases afforded me the best opportunity for a careful elaboration of these principles for practical purposes. I found that all these prin- ciples could be incorporated in a system of dosage, which be- gins with a certain amount of tuberculin, increasing the dose subsequently by a definite amount for a certain number of treatments and then increasing the increase at definite inter- vals until a reaction is reached. The reaction thus produced is mild, because it is produced by the smallest amount of tuberculin required to produce such a reaction in the indi- vidual, taking account of the increased tolerance produced by previous injections.- By increasing the intervals, after The harm such reaction, and decreasing the dose by a small amount, fromthe reactions to offset the decreased tolerance produced by the reaction, obtained by we know that we are using a quantity of tuberculin as nearly is ! ns 7gnincant exact for that particular indivdual as can be approxi- mated to produce the ideal therapeutic effect. For the next 54 TUBERCULIN AND VACCINE few treatments, therefore, the increase need be but slight in order to keep up' this full therapeutic effect, and so this increase is begun at this point as at the beginning of treat- ment, subsequently increasing this increase again, to make sure that we do not fall behind in producing the maximum effect. A second reaction may thus be reached and even a third, during a course of tuberculin treatment, and since these reactions cannot be but mild, the continued maximum effect produced by thus constantly keeping at the level of maximum tolerance, far outweighs the possible ill effect produced by such mild reactions. Explanation of Dosage Table I, (Page 57.) If the treatment requires that we begin .with the fifth Explanation dilution and having 0.10 c.c. as the first dose, the second dose would be 0.12 c.c., the third dose 0.14 c.c., thus increasing twice by 0.02 c.c. At the third dose, however, the increase should be increased by 0.02 c.c., the total increase therefore would be 0.04 c.c., making [the third tdose 0.18 c.c. We in- crease a second time by 0.04 c.c, making the fourth dose 0.22 c.c., again increase the increase by 0.02 c.c. at the fifth dose, making the total increase 0.06 c.c. and the fifth dose 0.28 c.c. At the sixth injection, the increase is the same as at the fifth, making the quantity of the sixth injection 0.34 c.c., but at the seventh injection we add 0.02 c.c. again to the increase, making the total increase now 0.08 c.c. and the quantity for the seventh injection will thus be 0.42 c.c., repeating the same increase for the eighth injection, we have as our eighth dose 0.50 c.c. This goes on, increasing the increase at every second treatment by 0.02 c.c, until a full cubic centimeter or mearly a full cubic centimeter is reached, when the treatment should begin with a 0.10 c.c. of the fourth dilution. Beginning again with an increase of 0.02 c.c. and continuing the dosage with the fourth dilu- tion as with the fifth dilution, so also with the third dilution and with the second, until the first dilution is reached. TUBEBCULIN TREATMENT 55 By the time the first dilution is reached, the tolerance of the patient is usually so high that the increase in the dosage may be increased at every injection, instead of at every other injection. Thus beginning with ,0.10 c.c. of the first dilution, the second treatment should be 0.12 c.c., which is an increase of 0.02 c.c. The third injection should be 0.16 c.c., being increased by 0.04 c.c., the fourth treat- ment is 0.22 c.c., which is an increase by 0.06 c.c. The fifth treatment is 0.30 c.c., making the increase 0.08 c.c., and so on until a full cubic centimeter of number one is reached, making the conclusion of the treatment with OT. A care- ful perusal of the Table of Dosage, page 57, will illustrate its simplicity. Should a constitutional reaction occur after any one of these injections, an interval of a full week is indi- cated before resuming treatment, commencing then with the third last dose as illustrated in Table of Dosage II, page 59, The treatment is then continued as before, but the amount of increase should be as at the commencement of treatment, no matter what the quantity of increase was before the reaction. Thus, if a reaction occurs after 0.18 c.c. of the fourth dilution, the next dose should be 0.12 c.c. of same dilution, followed by an increase of 0.02 c.c. for two con- secutive treatments, then by 0.04 c.c. for two consecutive treatments and so on as before. Table of Dosage II also illustrates the effect of a local reaction on the subsequent dosage that is, a local reaction has no effect on the quantity to be inoculated, but does require the lengthening of the interval to a week. Intervals Tuberculin injections should be given twice a week, Tuberculin is J . administered arranging for the new increase just before the longer twice weekly. of the two intervals. In administering two injections a week, we have an interval of two days and another of three days, and since the increase of the increase is made at every second injection, it could be so timed as to fall before the three dav interval. 56 TUBERCULIN AND VACCINE A local reaction should lengthen the interval before the next treatment to a full week. A focal reaction should not influence the course of the treatment except in isolated instances. A temperature reaction indicates a decrease in the next dose, an increase in the interval before the next dose to a full week, and the return to the original amounts of increases. A local reaction persisting at the time when the next treatment is due should indicate a postponement of the treatment, lengthening the interval to a week; a local reac- tion still persisting beyond a week has no further signifi- cance. Neither does a local reaction, when it is not accom- panied by a constitutional reaction, indicate a lessening of the dose. As I have stated in another chapter, a focal reaction is. merely a manifestation of the therapeutic and physiological action of the tuberculin and need not at any time indicate either reduction in dose or lengthening of interval. How- ever, in lung cases where there is a tendency for hemorrhage and the focal reaction brings forth blood streaked sputum, it is well to increase the interval to one week and in cases where the danger of hemorrhage is more pronounced, it is best not to increase the increase until this tendency dis- appears. An increase in dose by 0.02 c.c. or 0.04 c.c. can be maintained even during the presence of blood streaked sputum. The constitutional reaction indicates the increase of the interval to one week, and also a reduction in the amount of tuberculin making the treatment following the constitu- tional reaction equal to the third last dose and the return to the smallest increases as at the beginning of treatment. Should a constitutional reaction occur after the first treat- ment, the interval before the next treatment should be a week and, as was stated elsewhere, the treatment is re- sumed with one dilution higher. For example : If a reac- tion occurs after beginning treatment with a 0.10 c.c. of No. 4, the following injection should be 0.10 c.c. of No. 5. with treatment from there on as if dilution No. 5 were the first used. When 0.10 c.c of No. 5 at the first injection pro- duce a constitutional reaction, a sixth dilution must be made and used in the same dosage as dilution No. 5 would have been used. TUBERCULIN TREATMENT 57 Table of Dosage I SHOWING SCHEME OF DOSAGE WITHOUT REACTION No. of Dil. Quant Reaction Date Treat. No. per c. c. Local Temp. Jan. 1 1 V* 0. 10 5 2 0. 12 +0 .02 8 3 0. 14 +0 .02 12 4 0. 18 +0 .04 15 5 0. 22 +0 .04 19 6 - 0. 28 +0 .06 22 7 0. 34 +0 .06 26 8 0. 42 +0 .08 29 9 0. 50 +0 .08 Feb. 2 10 0. 60 +0 .10 5 11 0. 70 +0 .10 9 12 0. 82 +0 .12 12 13 IV 0. 10 16 14 0. 12 4-0 .02 19 15 0. 14 +0 .02 23 16 0. 18 +0 .04 26 17 0. 22 +0 .04 Mar. 1 18 0. 28 +0 .06 5 19 0. 34 +0 .06 8 20 0. 42 +0 .08 11 21 0. 50 +0 .08 15 22 0. 60 +0 .10 18 23 0. 70 +0 .10 22 24 0. 82 +0 .12 25 25 Ill 0. 10 29 26 , o. 12 +0 .02 Apr. 1 27 0. 14 +0 .02 5 28 0. 18 +0 .04 8 29 0. 22 +0 .04 12 30 0. 28 +0 .06 15 31 0. 34 +0 .06 19 32 0. 42 +0 .08 22 33 0. 50 +0 .08 58 TUBERCULIN AND VACCINE +0 . 10 +0.10 +0.12 +0.02 +0.02 +0.04 +0.04 +0.06 +0.06 +0.08 +0.08 +0.10 +0.10 +0.12 +0.02 +0.04 +0.06 +0.08 +0.10 +0.12 +0.14 +0.16 +0.18 * If reaction occurs after this dose, begin treatment with the sixth dilution. The dosage of the sixth dilution being the same as the fifth. f Double last dose as a test for any possible remaining hypersuscepti- bility. If there is a reaction to this dose, repeat the entire course of treatment with No. 1. 26 34 0.60 29 35 0.70 May 3 36 0.82 6 37 II 0.10 10 38 0.12 13 39 0.14 17 40 0.18 20 41 0.22 24 42 0.28 27 43 0.34 31 44 0.42 June 3 45 j 0.50 7 46 0.60 10 47 0.70 14 48 0.82 17 49 I 0.10 21 50 0.12 24 51 0.14 28 52 0.22 July 1 53 0.30 5 54 0.40 8 55 1 0.52 12 56 0.66 15 57 0.82 19 58 OT 0.10 26 59 0.20f TUBERCULIN TREATMENT 59 Table II SHOWING LOCAL THE EFFECT ON DOSAGE AND INTERVALS OF A REACTION AND A CONSTITUTIONAL REACTION No. of Oil. Quant. Reaction Date. Treat. No. per c. c. Local Temp. Jan. 1 1 V .10 5 2 .12 +0.02 8 3 .14 +0.02 12 4 .18 +0.04 15 5 .22 +0.04 19* 6 .28 ++ + +0.06 26* 7 .34 ++ +0.06 Feb. 2* 8 .42 + +0.08 9 9 .50 +0.08 12 10 .60 +0.10 16 11 .70 +0.10 19* 12 .82 ++ + 101 +0.12 26 13 .60 3d last dose Mar. 1 14 .62 +0.02 5 15 .64 + 0.02 8 16 .68 +0.04 11 17 .72 +0.04 15 18 .78 +0.06 18 19 .84 +0.06 22 20 .10 25 21 .12 +0.02 29 22 .14 +0.02 Apr. 1 23 .18 +0.04 etc. etc. etc. After each of the sixth, seventh, and eighth dose there was a local reaction with a temperature rise to 101, therefore there is an interval number of crosses (-)-) merely designates the severity of the local reaction: thus one cross indicates a mild, two crosses a moderately severe, and three crosses a severe local reaction. After the twelfth dose there was both a local and a constitutional reaction with a temperature rise to 101, therefore there is an interval of one week after the twelfth dose, and the quantity administered as a * Interval of one week. 60 TUBERCULIN AND VACCINE thirteenth dose reduced to the same as was given at the tenth inocula- tion. The fourteenth dose is only 0.02 c.c. larger than the dose given after the constitutional reaction or dose thirteen, for the increase after a constitutional reaction should be reduced to the same quantity .is at the beginning of trentincnt. Table III BACILLARY EMULSION AFTER OT No. of Dil. Quant Reaction Date. Treat. No. per c. c. Local Temp. Aug. 5 60 BE I 0. 10 12 61 0. 20 19 62 0. 30 26 63 0. 40 Sept. 2 64 0. 50 9 65 0. 60 16 66 0. 70 23 67 0. 80 30 68 0. 90 Oct. 7 69 BE Pure . 10 14 70 0. 20 In cases where there is complete clinical cure and where the BE is given to make sure that we obtain a bacillary immunity as well as toxic immunity, it may be given as rapidly as indicated in this chart. Table IV BACILLARY EMULSION AFTER OT. SLOW METHOD No. of Dil. Quant. Reaction Date. Treat. No. per c. c. Local Temp. Aug. 5 60 BE I 0.05 0.10 0.15 0.20 0.25 0.30 0.35 0.40 0.45 12 61 19 62 26 63 Sept. 2 64 9 65 16 66 23 67 30 68 TUBEECULIN TREATMENT 61 Oct. 7 69 0.50 14 TO 0.55 21 71 0.60 28 72 0.65 Nov. 4 73 , 0.70 11 74 0.75 18 75 0.80 25 76 0.85 Dec. 22 77 0.90 9 78 BE Pure 0.10 19 79 0.12 29 80 0.14 Jan. 7 81 0.16 17 82 0.18 27 83 0.20 Feb. 6 84 0.22 16 85 0.24 26 86 0.26 Mar. 5 87 0.28 15 88 0.30 In cases where complete clinical healing has not taken place by the time OT is concluded it is best to administer BE by this slow method in order to keep the patient under its influence during treatment for the local condition. Open bone and joint cases very frequently take longer to completely heal the local condition than it takes to complete a course of tuberculin. Also in pulmonary cases with a cavitation, the cicatrization of the cavities might take a great deal longer than it takes to gain complete tolerance. In such conditions the administra- tion of tuberculin should not be entirely discontinued until clinical healing has occurred. Chart I is a schematic representation of the relation of tuberculin to a patient's tolerance. A represents the mini- mum tolerance, a state where the patient has lost the immune response and is absolutely hopeless. C represents the level of maximum tolerance, a state where the toxic immunity is complete and the hypersuscepti- bility has disappeared. 62 TUBERCULIN AND VACCINE B represents the level of tolerance of a given tuberculous individual at the beginning of tuberculin treatment. Curve X-Y represents a maximum rise of tolerance with- out reaction and in response to an ideal method of tuberculin inoculation, were we in possession of an accurate method of measuring tuberculin to individual hypersusceptibility. (a) is a curve showing the influence of a tuberculin inoculation on the patient's tolerance when the first dose is too small to cause a reaction and the same dose is al- ways repeated; after producing no result for a while, it would soon increase the patient's hypersusceptibility and even lead to a more rapid progress of the disease. (b) is a curve showing the influence of a course of tuber- culin inoculations on the patient's tolerance when the first dose is less than the patient can tolerate without a reaction the dose being subsequently increased at every inoculation by the same amount the increase not being sufficient to make up the difference between the preceding dose and the amount that would bring it to maximum tolerance. The curve would rise for a while, but would soon lose in effective- ness, until the tuberculin would fail to produce any results whatever. (c) is a curve showing the influence of a course of tuber- culin inoculations on a patient's tolerance where the first dose is as it should be less than the patient can tolerate without reaction and where the dose is increased and the amount of increase also increased. It thus makes up for the amount of tolerance gained by each previous inoculation and gains upon the patient's increasing maximum point of tolerance. Owing to our inability to judge when we are near the maximum point of tolerance, we may even exceed it on several occasions producing a reaction. This for the moment lowers the patient's tolerance. But, this lost ground can easily be made up, if with a proper technique we avoid too great a reaction and therefore too great a set-back. Such a set-back is advantageous, as it serves as a guide to the most CJ i & x are infected through the tonsils ; or, whether the bacillus gains entrance through inhalation or infected food. What is of interest to us from a practical point of view, is that infants rarely die of tuberculosis of the lungs as a primary infec- tion; that as a general rule, the infections of bones and joints occur in children older than those affected with glands and younger than those suffering from infection of the lungs; and that nearly all glandular enlargements in individuals dying from causes other than tuberculosis were found to ,be tuberculous. These facts, together with the large mass of research in tubercular infections throughout the world seem to leave no room for doubt that such three stages of the infection exist and that tuberculosis of the glands is the primary form of the infection. We see case after case of tuberculosis of the glands of the neck followed by tuberculosis of the bone and if double infection occurs in FIG. 13. ILLUSTRATES THE THREE STAGES IN ONE INDIVIDUAL, GLANDS; BONE (sternoclavicular joint and sternum) ; LUNGS. This patient, a Chinaman, twenty-five years old, has had suppuration of the glands of the neck since early childhood. Several operations, two of them radical, were performed, but each time the wound failed to close. About two years ago, and directly after the last operation, the disease extended to the sternoclavicular joints on both sides. A cough developed which lasted for two years. On examination, both lungs were very extensively involved. He disappeared from the clinic after a few visits. We subsequently learned that he was discouraged from taking tuberculin treatment by other physicians (as if there was any chance for recovery by any other treatment). FIG. 14. ILLUSTRATES THE THREE STAGES IN A CHILD, GLANDS (neck and mediastinal) ; BONES (both hips) ; PULMONARY. This photograph represents a niore rapid progress of the disease, where little natural resistance could be developed during the spread from one stage of the disease to the other. TUBERCULOSIS OF THE GLANDS 69 a very young child, it finally dies of an extension into the lungs. In older individuals, the process will remain in the bone or joint, the glands perhaps showing a tendency to heal. The process then becomes very chronic, the resistance of the patient being sufficient to prevent an extension into the lungs, but not quite sufficient to put an end to the infection. It therefore follows, that since tuberculosis of the glands represents the primary lesion, it offers an ideal situation for the checking of the infection, and this should be pur 'main aim. The removal of the hypersusceptibility by a course of tuberculin will remove the probability of an extension of the disease. The healing of the local lesion is by far less important. Since the . . . glandular Too much attention has been paid to the local condition in form of the glandular tuberculosis and the efficacy of tuberculin treat- ^rellnts ment in tubercular glands was judged by ;the course of the the primary local process during the treatment. The success of tuber- offers the culin thus depended upon the presence or absence of co- ' deal SItuatlon for immuno- existing processes other than the tubercular affection; for therapy. we know that many processes can supervene upon a tuber- cular process which may remain after successful treatment Weare was directed against the tubercular process alone. If, on the a constitutional other hand, we remember the greater responsibilitv, that of , dlse f se> lts ' ' local mam- checking an infection which is in its primary stage, and festations give our attention to the local condition secondarily, the great ony secondary utility of tuberculin in tubercular infections would becom'j consideration. apparent to every one. The radical surgical operation is a severe incursion upon The ra di ca i the alreadv delicately balanced organism and the recurrence P er a tionis J a failure for is due to the tubercle bacillus left behind, not on account of the reason the lack of surgical skill, but because of the presence of the wiVthe^ocai tubercle bacilli which are beyond the reach of the knife, conditions alone, and The organism thus rendered more susceptible allows of a may do great greater spread of the disease than before the operation, r ^ in ^ the for the hypersusceptibilitv is greatly increased by any surg- natural Jr " . resistance of ical interference requiring a general anesthesia. the patient. 70 TUBERCULIN AND VACCINE Closed tubercular glands con- sist of two varieties, the hyperplastic glands which undergo caseation and softening and the fibrous glands with scar tissue formation. Classification. A more detailed classification with regard to the pathological processes involved in tubercular glands will greatly simplify the whole matter and will render much clearer the differentiation between the tubercular process and other pathological processes that may supervene. Once such differentiation is made, we shall know on the one hand what to expect of the tuberculin and! we shall recog- nize, on the other hand, the necessity for other therapeutic measures when they are indicated. Closed Glands Under this heading, we class all tubercular glands that are enlarged, but have not broken down. They remain as masses of various sizes with a process that is purely tubercular. Consequently, we have two varieties of closed glands each dependent upon one of the other of the two varieties of processes that tuberculosis gives rise to ; that is, hyperplastic and fibrous. To [the hyperplastic variety belong the glands where the glandular substance increases together with infiltration of the stroma, causing poor blood supply to the center of the gland. The center of the gland soon liquefies and finally forms a cold abscess, or soft gland. It may remain soft for a Jong time. If left alone, the soft gland will finally acquire a tryptic ferment which will digest its capsule, finally eating its way out to the surface and pro- duce very ugly scarring. This process resembles a sloughing process. It is therefore necessary at the outset to aspirate these glands and treat them as described in Part III, under " Surgical Treatment." The fibrous glands are those in which the individual has a fair amount of resistance and reacts to the tubercular pro- cess by fibrous tissue degeneration. The longer the process goes on, the denser becomes the fibrous tissue in these glands so that when a course of tuberculin has checked the tuber- cular infection, this fibrous tissue will contract to a greater or lesser extent as a result of complete healing. Since fibrous FIG. 15. ILLUSTRATES THE FIRST AND SECOND STAGE GLANDS OF THE NECK AND BONE. This patient, fifty-four years of age, has been suffering from the glandular and bone infection for fifty-one years. The spread from the glands in the neck to the bones and joints was very rapid, but here the progress remained very slow and although the disease spread from one joint to another, there was sufficient resistance to prevent the spread into the Ulna's. TUBERCULOSIS OF THE GLANDS 71 tissue does not entirely absorb, it will very frequently leave a hard nodule, the size of which depends upon the number of glands involved. (Fig. 16.) One can readily see the fallacy in the conclusion that tuberculin has not cured the patient if such a nodule persists But a slight experience is needed with the radical operation for the removal of these glands to appreciate the difference between an operation such as would be required before tuber- culin had been administered and one that would be sufficient to merely remove the cicatrized glands after tuberculin had been administered. ,(Fig. 17.) Open Glands. By open glands we mean glands that suppurated to the open glands surface. They are of two distinct varieties. Those that varieties" have broken down as a result of tryptic ferments, the < a ) those ft c i i -i 111 i 11 broken down discharge of which is sterile; and those tthat have broken by tryptic down through suppuration due ;to a mixed infection. Of the latter, there are two varieties: the suppurating hyper- broken down plastic variety (Figs. 6 (and 7) and the suppurating fibrous infection. variety. In the process of healing during a course of tuberculin, no difficulties will be [met with in the case of any of the open glands, except with the fibrous sup- purating variety. While it may happen that the mixed of the second, infection goes on to destroy all of the fibrous tissue, this is t ( wo ' ^""4",: not usually the case. A large amount of fibrous tissue will (O suppurating remain after both the tubercular and the mixed infection (2) suppurating have been checked, so that here again we have a case where fibrous - surgical interference may be necessary to complete " a cure." (See Part III.) Recurrent G-lands After Radical Operation. (Figs. 8 and 9.) A recurrence after radical operation may take place Postoperative immediately after the operation, preventing primary heal- r ^^ reot ing of the incision; the sutures break apart and a large two varieties: 72 TUBERCULIN AND VACCINE (a) Those recurring immediately after operation consisting mainly of mixed infection; (b) Those coming on slowly and some time after the operation. Three-grades of hypersus- ceptibility exist in tubercular . adentitis. suppurating area forms, with a mass of enlarged glands beneath it. The rapidity with which the glands enlarge, from an ,invisible size to a mass almost as large as previous to 'the operation, implies mixed infection, for the tubercu- lar process alone can not cause such rapid enlargement, However, the increased hypersusceptibility is a factor in the recurrence. .These patients will very often run high tem- peratures and show marked symptoms of toxemia. The treatment of the mixed infection as described in Part III of this work, must be persisted in until the temperature is reduced before tuberculin inoculations are begun. Another form consists of a recurrence some time after a seemingly successful operation. These glands, as a rule, come on more slowly, are of a purely tubercular character and should be treated as .closed glands, taking into account the heightened susceptibility. This increased hypersuscep- tibility may persist no matter how long an interval has elapsed between the operation and the tuberculin treatment. Glands enlarged through a tubercular process on the opposite side of the neck or anywhere else -in the body should be treated the same as recurrent glands, if they appear after a radical operation; that is, we must take into account the heightened susceptibility due to the operation, no matter whether the process is recurrent or newly formed. (Fig. 20.) General Hypersusceptibility We have three distinct grades of general hypersuscepti- bility to deal with in tubercular lynrphomata. The closed glands represent the Jowest grade of hypersusceptibility. That is easily .explained when we recall that the glands in the body are the filters and detain the infectious organisms on their way to the more vital organs. That is also the reason why glandular tuberculosis represents the primary infection with the tubercle bacillus. It therefore follows that so long as the glands remain closed, they are success- fully coping with the infectious organisms, although they are undergoing pathological changes as a result. As soon TUBERCULOSIS OF THE GLANDS 73 as these glands break down, they no longer serve as filters, extension of the process becomes more likely and thus repre- sents a heightened susceptibility. The third grade of hyper- susceptibility occurs in glands that appear as an active pro- cess in spite of and following .a radical operation. There is one exception to the general rule of hypersus- ceptibility in tubercular glands, and that is: after an infec- tious disease the jhypersuseeptibility is very high in any form of tubercular glands, even in case of the closed form, increase the This increase in hypersusceptibility bears no relation to the severity of the infectious disease, as !we may have a much to a marked larger increase in hypersusceptibility after a mild attack of grippe or varicella than iafter a severe scarlet fever. However, we must remember that an increase in hypersus- ceptibility does occur and must be taken account of if tuber- culin treatment is resorted to before six months have elapsed. We have all noticed the frequency with which tubercular pro- cesses in children first make their appearance after a conta- gious disease. That is most likely due to heightened sus- ceptibility as a result of the infectious disease, rendering a quiescent lesion active. (See Temperature Charts, page 151, 152.) Beginning Treatment. From the above, it follows that in the treatment of The beginning closed tubercular glands, 0.0001 c.c. of tuberculin or 0.10 t be r u i in . c.c. of the third dilution would not be too large a begin- ning dose. In the open tubercular glands, 0.00001 c.c. or 0.10 c.c. of the fourth dilution would be less likely to give a reaction from the first dose. In cases follow- ing a radical operation, 0.000001 c.c of tuberculin or 0.10 c.c of the fifth dilution should be the beginning dose if the recurrence appears immediately after the operation. If the recurrence does not appear until some time after the operation and the patient seems in good physical condition, 0.00001 c.c. or 0.10 c.c of the fourth dilution should be the beginning dose. The same holds true in tubercular glands 74 TUBERCULIN AND VACCINE if the treatment is begun before the elapse of six months after contagious disease, when 0.000001 c.c. or 0.10 c.c. of the fifth dilution is a, safe dose to begin with. Occasionally the hypersusceptibility is so marked as evidenced by a daily temperature rise and by a marked irritability of the patient, that the sixth dilution should be made and the treatment be- gun with a 0.10 c.c. making the beginning dose 0.0000001 c.c. of tuberculin. In the treatment of Orientals or negroes, one- tenth the quantity advised as beginning treatment above should be the beginning dose under similar conditions. Conclusion of Treatment. The conclusion In glandular tuberculosis, it is rarely necessary to con- clude the tuberculin treatment in any way other than is shown on ,the general scheme of dosage, as described in the last chapter. After the administration of the BE the patient returns every three months for test inoculation to determine whether there is a tendency for the return pf hypersuscepti- bility. The method of testing will be described more fully under its own heading. (See page 147.) Results. The results The results obtained from the treatment of tubercular have been glands with tuberculin leave no 'doubt that tuberculin is the treatment par excellence for this condition. Among others good where * tuberculin the late Doctor John B. Murphy, of Chicago, found that in adopted. a number of years no case of glands of rthe neck required operation where a course of tuberculin had first been given. That the radical operation is contra-indicated in every case of tubercular glands is beyond dispute. Those that still resort to the radical operation will find the responsibility harder to shoulder with the ever increasing recognition of the fact that glands can be cured without it. There are those who deny that tuberculin will cure all cases of glands. This denial may be based upon the expectation that tuberculin should not only cure the infection, but must eradicate every TUBERCULOSIS OF THE GLANDS 75 sign of the disease. Many have " tried " tuberculin and The radical have discontinued every other treatment. And when tuber- ^beroTiar r culin failed to remove a mixed infection, or when tuber- * landsis ' contra-indicated culm eradicated the tubercular infection but left behind a under an mass of fibrous tissues which could not be absorbed, these masses were pointed out l as the original glands and it was if u does not declared that tuberculin had failed in its therapeutic effects, traces of Granting that a surgeon honestly believes that glands en- atTetstTi'mit larged through tuberculosis ought to be removed, he ought surgical , , . j'lj-i i i interference even then to take cognizance 01 the tact that tuberculosis is to the a systemic disease and ought in every case rid the system of removal of * > a cicatrized the hypersusceptibllity before resorting to surgery for the mass which local condition. If this fact were always considered, the absorbed. whole problem would automatically adjust itself to all forms of opinion. For, the surgeon would observe the large number of patients who get well without operation. He would also notice that when an operation is performed after tuberculin, the fact that no recurrence takes place would more than emphasize the advisability of a course of tuberculin before operation. In hospital, as well as in private practice, I have had uni- formly good results iwith tuberculin in the treatment of glandular tuberculosis. In only /two cases was an operation necessary and both these cases were post-operative recurrent glands. One patient (Fig. 17) had had a radical operation for cervical adenitis, with recurrence in the submaxillary region. Applying for treatment about four months after the radical operation, we found the incision for the radical operation extended from the tip of the mastoid to two inches above the clavicle, then at right angles across the neck to the sterno- clavicular joint. The lower half of the horizontal incision was suppurating and consisted of a large granulating sur- face. She also presented a very high grade of hypersuscepti- bility with a mass in the submaxillary region the size of a hen's egg on the same side where the operation was per- formed. This mass, during treatment, reduced to the size of a walnut, but persisted after the conclusion of the course 76 TUBERCULIN AND VACCINE of tuberculin. Under local cocain anesthesia and through a half-inch incision, the mass was removed, the incision clos- ing by primary union, leaving an almost invisible scar. The removed mass consisted of a very dense fibrous tissue with hardly a vestige of glandular substance to be seen. During the tuberculin treatment, the patient gained twenty pounds in weight, and lost the nervous irritability and tremor of the hands which she had when she first presented herself for treatment. The second case, a woman twenty-nine years of age, with a negative family history, was always well before the present complaint and did not remember any diseases of childhood. At the age of fifteen, the glands of the neck on both sides began to swell; and until six years ago, the swelling con- tinued, sometimes in a milder form, sometimes very marked, at times almost disappearing on one side and then on the other, but iat no time was she free from enlargement of the glands of the neck. Six years ago she suddenly developed a painful enlarge- ment of her whole abdomen, the pain being specially marked in walking and from any jar whatsoever. About a month later, an exploratory laparotomy was performed and exten- sive tubercular peritonitis was discovered. Thirty ounces of fluid were removed and the peritoneal cavity exposed to the air and sunlight for " one hour." Xine days after this operation the abdominal cavity refilled, and after remaining confined to her bed for six weeks she was sent to a sanitarium in the mountains where she improved, the fluid disappearing from the abdomen after a period of six months. One year later, the glands of the neck, which were of the closed variety up to the present time, began t/> suppurate, especially the sublingual mass. Under a general anesthesia and through an incision extending from the angle of the lower jaw on one side to the same point on the other side a complete removal of this mass of suppurating glands was thought to have been carried out, but soon after the opera- tion the mass recurred, and the incision suppurated at several TUBERCULOSIS OF THE GLANDS 77 points. A month or two later, another radical procedure was carried out over a suppurating supraclavicular mass on the right side, with no better result; and during the year fol- lowing, six more general anesthesias were administered to the patient for the removal of one mass after another in both the cervical regions on both sides of the neck the supra- clavicular region on the left side, and in the suprasternal region. The posterior cervical chains suppurated on both sides but no attempt for their removal was made. Soon after the last operation on the neck, and two years after the first abdominal operation, the upper right abdomen began to swell and in the course of the following few weeks two large abdo- minal abscesses were opened and drained. These abscesses did not penetrate into the abdominal cavity and healed in a few weeks. About eight months later, an acute swelling of the abdomen again occurred with symptoms of peritonitis, such as abdominal rigidity, nausea and vomiting. Laparo- tomy was performed through the former median incision. A suppurating appendix was removed and a number of tuber- cular masses were found and removed. The patient recovered from this operation, but suppuration of the incision occurred with the formation of a fecal fistula. Soon after this opera- tion, a large mass of glands in the right axilla developed which suppurated a few months later. The patient applied for tuberculin treatment several months after the last abdo- minal operation (March 30, 1914). She weighed 130 pounds although she is five feet eight inches tall, was very pale, and highly neurotic. Around the neck, including both supra- clavicular and suprasternal regions, the anterior and poste- rior cervical and the sublingual regions were studded with openings from suppurating glands (about fifteen in all) r oozing a thick creamy pus. The lower jaw gave the ap- pearance of acromegaly from the Distortion brought about by the enlargement of the submaxillary and sublingual glands. The abdominal wall showed two longitudinal scars in the upper left quadrant and a median scar running from the umbilicus to the symphasis pubic. In the lower part of 78 TUBERCULIN AND VACCINE the median scar and about one-half inch above the symphasis there was a fistulous opening from which oozed a thick creamy pus, and after physic had been taken this would dis- charge feces. The tuberculin treatment continued uninter- ruptedly until April i9, 1915, and except for a few mild con- stitutional reactions and a number of severe local reactions the patient improved steadily, weighing 180 pounds at this time. Five masses persisted beyond this treatment, three on the left side and two on the right side of the neck. The two masses on the right side were removed under cocain anes- thesia with primary union. In August, 1916, I performed an operation for the relief of the fecal fistula, and at the same time removed one more mass on the left side of the neck. Outside of tuberculin, a vaccine for mixed infection was administered during her treatment, and just before the operation for the removal of the fecal fistula, three prophy- lactic inoculations of strepto-fecalis and colon bacillus were administered a week apart: First dose strepto-fecalis 250 mil. Colon bacillus 250 mil. Second dose strepto-fecalis 500 mil. Colon bacillus 500 mil. Third dose strepto-fecalis 1000 mil. Colon bacillus 1000 mil. The important points to be noted in this case are : 1. The rapid extension of the tubercular process to all the glands of the neck and their final breaking down did not take place until after a major surgical operation (laparo- tomy) was performed although the glands were diseased for many years before. 2. The tubercular affection of the glands is only a local manifestation of a constitutional disease. The attempted extensive operation for the relief of the local process only lowered the resistance of the patient, allowing the dis- ease to get a firmer hold on the constitution, which mani- fested itself at some point of lessened resistance most often at the point of operation and sometimes in more TUBERCULOSIS OF THE GLANDS 79 vital organs which happened to be in a state of lowered resistance. 3. Masses of fibrous tissue may become foreign tumors after the infection (disease) has been eradicated, and may require removal. 4. The removal of these masses is infinitely simpler and safer after the constitutional disease has been overcome. 5. Although at the first two laparotomies, extensive tuber- cular peritonitis was found, there was no sign of peri- toneal involvement found at the laparotomy for the cure of the fecal fistula performed after the tuberculin treat- ment. 6. Prophylactic immunization with stock vaccine of bac- teria found by a bacteriological examination of the fistu- lous discharge made a cure by one operation possible. (See Part III.) In both these above cases it will be seen jhow much more effective surgery is when applied in a condition that is purely local than in a similar condition when the local mani- Tuberculin festation is still a manifestation of a systemic condition, iniooper* With Petruschky and Kramer, I hold that tuberculin will "*<>* * J of adenitis. effect a cure in 100 per cent, of cases. From extensive experience in recurrent cases after radical operation, I maintain that the radical operation cannot be justified in any case; and in a child under five years of age, it is criminal ; for, in those cases a resistance has not been built up to any degree and a general dissemination is very immi- nent. The following is a case to illustrate this point. Willie K., born in September, 1913, whose family history was negative, had a normal birth and was Always well. On September 1, 1914, a swelling was noticed on the left side of his neck. This grew larger until November 20th, when a radical operation for the removal of tubercular glands was resorted to, the incision extending for three inches along the inner border of the sternocleidomastoid muscle. The wound reopened soon after the operation, forming a granulating sur- 80 TUBERCULIN AND VACCINE face occupying nearly the entire side of the neck. When the child was brought under ray care on February 10, 1915, his temperature ranged for a week previous between 101 F. and 105 F. daily, the wound in the neck consisted of an oval depression about two and one-half inches long and one-half inch wide, with) the edges composed 1 of thick granulat- ing tissue. From the center of the ,wound oozed a thick creamy pus. A chain of enlarged glands ran parallel to the outer border of the sternocleidomastoid muscle with one enlarged gland beneath the lower angle of the wound. Al- ready a tendency for the dissemination of the tubercular pro- cess made itself evident by the appearance of two distinct lupus spots on the shoulder and chest. I did not seek to clear the mixed infection by vaccine before beginning with the tuberculin treatment, owing to the tendency for the dissem- ination of the tubercular process and the length of time that the mixed infection had persisted (nearly three months). I have here inserted a chart showing nearly the entire course of treatment in this case. I did so because of several other important points which the case illustrates and which come up in the treatment of children. Child R Age 17 ,mos., male, diagnosis tubercular adenitis. 1915 No. Quant. Reaction Date No. Dil. per c. c. Local Temp Wgt. Feb. 15 1 IV 0. 10* 104. 5 20 Ibs. 19 2 ft 0. 12* 103. 8 22 3 " 0. 16* 103 25 4 tt .22* - h++t 103. 6 Mar. 5 5 (I 0. 10 - 102. 8 9 6 a 0. 12 101. 4 14 7 tt 0. 14 100. 4 21 8 it 0. 18 100 * To hasten the treatment the increase was increased at every inoculation. \ fThe distinct local reaction indicates that the slightly greater rise in temperature is a constitutional reaction. FIG. 10. AN EXAMPLE OF HARD CICATRIZED GLANDS AFTER CONNECTIVE TISSUE CHANGE. This scar is the result of an operation for the removal of a large mass of glands in the supraclavicular region. The patient applied for treatment six months after the operation on account of the failure of the wound to close. It had formed a wide granulating surface, and had the appearance of a mass of glands in the cervical region. The patient is still under treatment. Both the operation and the fact that she is Italian are responsible for a very high degree of hyper- susceptibility, which is making the tuberculin treatment unusually pro- longed in her case, although the wound promptly closed after a few weeks of treatment. These glands cannot completely absorb, not on account of any deficiency in the therapeutic value of tuberculin, but because cicatrized connective tissue rarely absorbs. After the hyper- susceptibility is removed by tuberculin, a small incision will be suffi- cient to remove the mass of cicatrized glands. The healing of the inci- sion by primary union will be no less assured than in the case of any other non-infectious operation. FIG. 17. SHOWS THE DIFFERENCE BETWEEN A EADICAL OPERATION BE- FORE TUBERCULIN TREATMENT AND A COSMETIC OPERATION AFTER TUBERCULIN TREATMENT. The scar was very prominent when the patient first presented herself for treatment at the New York Polyclinic Hospital, four months after the radical operation performed elsewhere. The angle of the scar was suppurating at the time. In order to show the extent of the incision for the radical operation it had to be painted with iodine just before this photograph was taken, so much has the scar absorbed during the tuberculin treatment. This photograph illustrates another bad feature of the radical opera- tion, especially when the chain of glands extends over the region of the spinal accessory nerve. Evidently the nerve was injured during the operation with the resulting dropped shoulder. The nerve supply to the deltoid muscle was also injured as there is very limited motion to the shoulder with considerable atrophy. The scar resulting from the removal of the submaxillary gland is barely visible. FIG. 18. OPEN TUBERCULAR GLANDS CAN A RADICAL OPERATION CURE THIS PATIENT? The tubercular process is not only in the suprasternal, supraclavi- cular and anterior cervical glands but in the superficial chain along the inferior border of the lower jaw from the right ear lobe to the chin, also involving the submaxillary gland on that side. Because of a very high degree of hypersensitiveness the treatment of this patient was very long drawn out. FIG. 19. OPEX TUBERCULAR GLANDS CAN A RADICAL OPERATION CURE THIS PATIENT? Following an operation for the removal of a mass of tubercular glands in the right axilla, extensive suppuration took place in the inci- sion, soon followed by the appearance of tubercular glands in the neck, as shown in this illustration. The susceptibility at the commencement of treatment was very high, rendering the treatment longer than usual. FIG. 20. ILLUSTRATES A EADICAL OPERATION WITH EXTENSIVE KECUR- EEXCE A FEW MONTHS AFTER THE OPERATION. FIG. 21. ILLUSTRATES A RADICAL OPERATION WITH IMMEDIATE RECUR- RENCE, WITH THE EXTENSION OF THE PROCESS TO THE APEX OF THE LUNG. The patient, a young man thirty years of age, born in the United States, a clerk by occupation, had a maternal uncle who died of pul- monary tuberculosis. Jn his childhood he lived with this uncle during the active stage of the disease. He had measles ,and whooping-cough in early childhood, and outside of frequent sore throats, was well until his sixteenth year. Fourteen years ago, he noticed ( that the glands on the right side of his neck (cervical region) began to swell. In six months they grew to such size that an operation was advised, and performed under a general anesthesia. One week after this operation, the wound suppurated, swellings appeared in the parotid region in the supraclavi- cular region, and in the entire posterior, cervical chain. These all broke down, so that after five months of invalidism, another operation was declared necessary, and performed under a two-hour general anesthesia. The patient stated that the surgeons declared " that it was necessary to go down to the jugular vein and to the lung in order to remove all traces of the disease." A month after this operation, four or five " lumps " appeared on the same side in the posterior cervical region, which he carried for five years, ,being unable all that time to wear a collar on account of their awkward position and the sentitiveness of the scars. Seven years ago, these swellings suddenly began to sup- purate. An operation was again performed under general anesthesia. Three days after this operation, the whole wound broke open with a great deal of sloughing of tissues. The patient declared that for three months " the hole in the side of his neck was large enough to admit a fist." After a great deal of local treatment lasting over a period of nine months the wound finally granulated and closed. Fig. 10 shows the extensive scarring of the side of the neck which was the seat of the tubercular process up to the present. In June, 1916, or five months before the patient was referred to me for tubc'iriilin treatment, he noticed that the right side of his neck was rapidly swelling, becoming steadily larger until the mass occupied the entire side of his neck as shown in Fig. 23. Treatment was commenced at once. And although these glands were closed, 1 began with the fourth dilution en account of the previous radical operations. He ran a slight temperature when he first started, going up to 99.4 F. by mouth every afternoon. There were several local reactions after the first few treatments. After the eighth inoculation, he had his first con- stitutional reaction, in which the temperature rose to ,100 F., the local reaction being at the same time quite severe and the constitutional symptoms being very definite. Both the local reactions and the constitutional reaction have greatly retarded his tuberculin treatment; but it is not the quantity of tuber- culin nor the frequency of inoculations that influence the therapeutic effects of tuberculin; it is the proximity of the dose to the maximum tolerance that makes it most effective. Fig. 24 shows the same young man barely four months after the beginning of the tuberculin treatment. The swelling in his neck has entirely disappeared, he is gaining in weight, and he has returned to his occupation which he is now able to pursue without interruption. .oi'I ff mod ,vt lo eiB97, v,taid:t nKm S7, ' .inoiinq ntfT -h;q lo baib odw glortr/ Ifurcxtaoi B had .norJuqu'rio yd Mo ^iinub alarm *id) dJiv/ boYtl 9d boodblida *id nl .aiaoliKnadfti ni dyno'cyniqoodw bna eIB90i bfid dH . *-.id liJnu Hay/ BV/ ^fto'fdt 9'io hrgnpg'il lo 9bi*)no Urn; ,boodblid'j odJ no *brruh> odi idt, baatfou 9d ,o^>.'; <-'n;ay negj-njol .Ti;ay iLh HlJnoiii /i* ill .H-iwfi oi nf;g9d (noii;)i [BDJYT&O) vlo'jri "id V. IrjrmoVi.oq bni; , .v noit/i-nqi) IIB jBiJi o?;i>i dun>. o; ;()'// -JiiO .;;t''>if^'jr/i lurwvu B -labnu ui rroi teq 9ffJ ni Jwrc'xjfj/s ^nifl97/ ,! HB 9feodT .ffiiiif'; li/ji',";-)') ,'tuh :> oil) ni Inrr, ,i. uoiiBisqo -I'll.' .ifjvni lo ^iftnorn 97ft -igJls indJ moil U//1 i; -I'-dnin Lorifnyl'iyq J>HB . viaaeaaaa arrw .Ji' . t JfiilJ bo: ,..ij --jdT llu -.vofno-i oJ 1 i9bio ni i>/rr/[ od) o^ brrn ni-iy iclnyuj 9dl oj nv/ol >/il -io -inol .fioij/rtaqo airi^ iiJlu dinoin A ".9j?o>;ib adi .noiii'/i Ii;'jirt99 loiToigoq 9d^ ni ebia 9fUB>- orfj n t.i tfionavi^iiOM 9rf) bns noiiiaoq bi/3W}I'/7B ligd-t lo iiifioo-jii no 'iBlIo-) l.-')ifi^9irn [eieodg i9bnu baorroligq niB^B RBVA /ioiJi; > ti(|o nA .oirnuq <; diiv/ noqo 9/Ioid bmmv/ gfodw 9di ,noi^B79qo aid)' Tail B ^vr;i> 09'fdj tol i/;d) Iwtfil'jgb inoitfiq yfIT .89i/aii lu jmiikmolr-. lo IB-)!) irrbc oi /(yjroiro agisl %C7/ ^')9n aid lo 9bia gdJ 1 ni olod 9dd^ " edjrioirr trciu lo bohgq B 1970 gnii^Bl JnenrfrBgiJ IBOO! lo I69b ^Ba-tg t> -igJlA ".jxil n)i r.-tnnlf. Of .i1 .boeola bnn bgJBlunfi-ig yJLBnil bni/ow adi ii) lo JB9-i art* en?/ doidw jJagn gdi lo sbia 9dJ lo gnrmi .Jn9R9iq nifl oJ qr; ^r-.o-jo-i am oj bgiialoi 8 Bv/ Jnoitaq 9dJ 9-iolg.J ariinom 9yft -to .OJftf , bgoilon ad ,in9in)nod niln-rfsdnl TO! adj baiquaao asfioi 9dj Him/ -tygiRl ylibiieis gnimo-vtil .^aillav/- /fbiqB-r b93ff9inmoa BBW InemifsgiT .S .i1 ni nwoxte es iasn Bid io .JJ.IH 'otilno .Jrv/ fiB^ad i ( fiecof9 slaw sbnfilg sasriJ d^uoiljlB bnA .* .anoilB-wqo luaibsi euoiysiq 9di lo innoooj; no nottulib 7'1 .'H i-.ee o* qu S nio^ ,b9iiBJa dain 9 d ngdw yusii-.^im-.t -too i.-iB r.irf barf if .HOfJalwoooi rild^b ad* igJIA >];, >! h ,',, > v/aTj^'fl ./* "001 o* 9,01 9-,ui 1 9qm9i add doidy, ni .,-; ,,,,-, l.rroiiulir, J.fciio-) 9((1 bnn 9W/SH 9*inp 9mit 9 a,Ba 9d* ), -.,,;. I . r/Bd noitown rBnoittiiaoo 9dj boa anoUoam IBOO! 1f f; , tfiteaup Sf fj * 0r e{ t odJ wn^Rnj J(MU edl oi 9 ob ,di lo lo tfiteaup Sf fj * 0r e{ H jffd . in , mjB9li ni[u ,,. )(Il;j .: ' lo omn. edi e -,oda *2 . 8 iT . 9vlJwR3 , 80ra JZ Wilafn }t;(ft ".mtB^t iffo-mdnl edi lo a r,mni ed o.ii ,,,n : 8 rf*nom TOO 1 ^sd nnrrr :- 9 d .b9-rB9qq,ib ylonino 6 ,l * , if( n{ ' '"f fhhlw aif f)fin .. FIG. 22. POST-OPERATIVE EECURRENT GLANDS. This case illustrates the futility of any operation which aims to remove the local manifestations of a constitutional disease. (See pages 83 and 84). FIG. 23. POST-OPERATIVE KECURREXT GLANDS. The right side of the neck of same patient as Fig, 22 when tuberculin treatment was commenced. TUBERCULOSIS OF THE GLANDS 81 Mar. 25 IV 29 10 " Apr. 5 11 " 12 12 " 16 13 " 19 14 " 26 15 " May 3 16 " 7 17 10 18 " 17 19 24 20 " 31 21 " June 7 22 " 11 23 " 19 24 " 22 25 " 26 26 " 30 27 " July 6 28 " NOTE 1. The first four inoculations represent an increase of the increase at every inoculation instead of at every other inoculation. 1 did this in order to reach the maximum of tolerance as soon as possible having begun with the fourth dilution, because it was a post-operative case. I felt that if the hypersusceptibility happened not to be increased by the operation there would be an unnecessary delay in reaching the maximum tolerance. A distinct reaction after the fourth inoculation pointed to the fact that the beginning of treatment with the fourth dilution was correct in this case, and that from the start I was fairly near the maximum of the child's tolerance. That explained the rapid drop in temperature from the very beginning of treatment. The reason why I considered 103.6 F. as a distinct con- stitutional reaction was the fact that there was a severe local reaction accompanying the rise in temperature of 0.6 of a degree higher than the maximum temperature for three or four days previous to this inocu- JTemperature record neglected but slight local reaction present, hence, dose not increased. ([Temperature reaction after this inoculation proves that a reac- tion had occurred after last dose. fiThis dose should have been 0.48 c.c. which might have avoided the reaction. 6 0.22 100.2 0.28 + t 22.5 Ibs. 0.28 -t -+ + 102.211 0.18 100 0.20 100.4 0.22 ++ 101.8 0.14 Normal 0.16 u 0.18 a 0.20 +'+ " 23.5 Ibs. 0.24 + u 0.28 + ti 0.34 ++ " > 0.40 a 0.50H -J-_l_ 102.4 V V || 0.34 Normal 0.36 a 0.38 tt 0.42 " 0.46 " 25.5 Ibs. 82 TUBERCULIN AND VACCINE lation. If there were no local reaction at the point of inoculation on the arm, even a much higher rise would not be considered a constitu- tional reaction, but would be attributed to a larger amount of absorp- tion from the wound area or to some intestinal derangement, etc., occur- rences which are so frequent in children at that age. Analysis of the tenth inoculation which was given on the 29th of March, illustrates a common occurrence in the treatment of children where the mother has all the household duties and the care of the patient on her own hands. When the mother brought the child on April 5th, I found a mild reaction as represented by one plus (-}-) from the previous inoculation, the mother reporting that she was too busy to take temperatures. I therefore repeated the same dose on the 5th of April that I gave on the 29th of March for this reason: with a local reaction present, there might or might not have been a constitutional reaction, after the previous inoculation. If there was a constitutional reaction, the same dose will produce a constitutional reaction again. - The second constitutional reaction may be slightly more severe, but will avoid too great a drop in. the dose in case it was found that no reaction had occurred. In this case, there was a severe local reaction and a moderate constitutional reaction, proving that the dose previous had also produced a reaction. But if the eleventh inoculation had not produced a reaction, there would have been a loss of one inoculation, whereas, if we had not made this test and the eleventh inoculation would have been 0.18 we would have lost nearly one month of treat- ment before the maximum would again have been reached. It is always advisable in case of a doubtful constitutional reaction to repeat the last dose before reducing the amount of tuberculin. After the fourteenth dose, on April 19, there was a rise in tempera- ture to 101 F. which I considered a distinct reaction on account of the local reaction present. Owing to the fact that this reaction occurred so soon after the last one, a larger reduction in dose than usual was made; that is, I reduced the dose to the amount to which it would have been reduced had the reaction occurred after the first time 0.22 c.c. had been administered, as at the ninth inoculation. Subsequently, and for the same reason, I increased, by 0.02, the three following inocula- tions instead of only two, and after the eighteenth inoculation, continued in the usual manner. However, on account of the local reactions, occur- ring four times in succession after the eighteenth dose, the inoculations could be given only once a week. After the twenty-third inoculation, there was a distinct constitutional reaction occurring as a result of an error in the amount of the increase. There should have been an increase of 0.08 c.c. instead of 0.10 c.c. Although the rise of temperature was to 102.4 F. the constitutional symptoms were mild, the rise in tempera- ture in a child at that age being usually out of proportion to the cause. The usual indications were followed ; that is, after a wait of a full week, the treatment was resumed with an amount of tuberculin equal to the third last inoculation with the increases from /there on as at the begin- ning of the treatment. TUBERCULOSIS OF THE GLANDS 83 From the end of April, the wound began to contract and the dis- charge diminished day by day until the beginning of June, when the wound closed completely. After the inoculation of June 11, it discharged slightly from the upper angle but soon closed again and never reopened. The treatment was continued without any further interruption until the end of November, at which time no trace of disease remained, except the linear scar marking the place of the operation. It may be noted that my original conclusions as to the mixed infection were correct. The wound was so shallow that with the disappearance of the tubercular process, the consequent improvement of the general health was sufficient to overcome the mixed infection. The following case illustrates the futility of any opera- tion which aims to remove the local manifestations of a con- stitutional disease. The patient, a young man thirty years of age, born in the United States, a clerk by occupation, "had a maternal uncle who died of pulmonary tuberculosis. In his childhood he lived with this uncle during the active stage of the disease. He had measles and whooping-cough in early childhood, and outside of frequent sore throats, was well until his sixteenth year. Fourteen years ago, he noticed that the glands on. the right side of his neck (cervical region) began to swell. In six months they grew to such size that an operation was ad- vised, and performed under a general anesthesia. One week after this operation, the wound suppurated, swellings ap- peared in the parotid region in the supraclavicular region, and in the entire posterior, cervical chain. These all broke down so that after five months of invalidism, another opera- tion was declared necessary, and performed under a two- hour general anesthesia. The patient stated that the stuv geons declared " that it was necessary to go down to the jugular vein and to the lung in order to remove all traces of the disease." A month after this operation, four or five " lumps " appeared on the same side in the posterior cervical region, which remained for five years. He was unable all that time to wear a collar on account of their awkward posi- tion and the sensitiveness of the scars. Seven years ago, these swellings suddenly began to suppurate. An operation was again performed under general anesthesia. Three days 84 TUBERCULIN AND VACCINE after this operation, the whole wound broke open with a great deal of sloughing of tissues. The patient declared that for three months " the hole in the side of his neck was large enough to admit a fist." After a great deal of local treat- ment lasting over a period of nine months the wound finally granulated and closed. Fig. 22 shows the extensive scarring of the side of the neck which was the seat of the tubercular process up to the present In June, 1916, or five months before the patient was referred to me for tuberculin treatment, he noticed that the right side of his neck was rapidly swelling, becoming steadily larger until the mass occupied the entire side of his neck as shown in Fig. 23. Treatment was commenced at once. And although these glands were closed, I began with the fourth dilution on account of the previous radical operations. He ran a slight temperature when he first started, going up to 99.4 F. by mouth every afternoon. There were several local reactions after the first few treatments. After the eighth inoculation, he had his first constitutional reaction, in which the temperature rose to 100 F., the local reaction being at the same time quite severe and the constitutional symptoms being very definite. Both the local reactions and the constitutional reaction have greatly retarded his tuberculin treatment ; but it is not the quantity of tuberculin nor the frequency of inoculations that influence the therapeutic effects of tuberculin ; it is the proximity of the dose to the maximum tolerance that makes it most effective. Fig. 24 shows the same young man barely four months after the beginning of the tuberculin treatment. The swelling in his neck has entirely disappeared, he is gain- ing in weight, and he has returned to his occupation which he is now able to pursue without interruption. FIG. 24. POST-OPERATIVE EECURRENT GLANDS. The right side of the neck of same patient as Fig. 22 four months after tuberculin treatment has been administered. CHAPTER IV BOXE AKD JOINT TUBERCULOSIS The subject of bone and joint tuberculosis stands next in importance to pulmonary tuberculosis. And that only as regards the number of cases afflicted, for it stands second to none in the gravity of the problem it presents. Attack- pulmonary ing as it does its victims in childhood and early adolescence, tuberculosis it at once affects the individual as to his entire future exist- ma ny S more ence, no matter how mild a course the disease mav run. victims> bone and joint On the one hand, it prevents the proper fundamental edu- tuberculosis cation which one can acquire only at that age ; and on the a pro bi e m * other hand, it disorganizes his phvsical makeup, interfer- bothwlth regard to the ing with or even preventing any occupation which would effect of the keep him from becoming a burden on society. There is the victim, nothing so much the subject of pitv as a cripple, no matter andwith regard to the what the cause may be. But when added to the deformity status of the we have invalidism, as in a case of tuberculosis of the joint, the community, it is lamentable. A physically deformed individual in the course of years becomes accustomed to the deformity and with the finding of an occupation that has become suited to his condition, may even learn to enjoy the pleasures of life with but an occasional sting coming from the consciousness of his being deformed. But when this deformity is caused by tuberculosis, especially open tuberculosis, with discharg- ing sinuses, the gradual diversion of the mind towards the ordinary pursuits is prevented by the necessity of constantly nursing his wounds and by the pain and discomforts which confine him to his bed or to limited activity beyond it. In its progress, medical science seems to have over- looked this pitiful army of suffering children. The best proof that the profession seems to have abandoned these unfortunates as hopeless, is the tendency to convert hos- pitals for tuberculosis cripples to " homes " for crippled 86 TUBERCULIN AND VACCINE Up to the present time these "homes" can only accommodate a small fraction of the victims. children, with the establishment of educational systems. The name " home " to signify the permanency of residence and the institution of the educational system has come in answer to the law requiring universal education. Fortun- ately it also serves the greater purpose of occupying the minds of these sufferers for at least part of the ^lay and of diverting them from their miseries. The number of children taken care of in " homes " is insignificant in comparison with the great army of crippled children throughout the land, who are unable to get accom- modations in such " homes." And if the lot of those in the " homes " and hospitals is so pitiful, what can be the lot of those children who are kept in the homes of the poor? How much care and attention can a crippled child get in the home, where the burden of the care of a number of other children falls upon the mother in: addition to the care of the home, and where even the support of the family frequently falls to her lot ? In the case of bone and joint tuberculosis, an efficient remedy would be welcomed almost as enthusiastically as one for pulmonary tuberculosis. What then has prevented the wider adoption of tuberculin in the treatment of bone and joint tuberculosis ? With the brilliant results obtained by the use of bismuth paste, as [reported by Beck, con- stantly before us, why has it not been more widely adopted by the medical profession ? No one can doubt the efficiency of Bier's hyperemia in tuberculosis of the bones and joints; nor can we question the veracity of its author's reports of his success in a large number of cases. Why have we not adopted this method more generally in the treatment of the bone and joint condition ? Favorable reports from the use of vaccines in discharging sinuses are coming from unques- tionable sources, especially from England. What is the reason that we are so slow in adopting the vaccine treat- ment of these conditions? There is but one answer to all these questions and that BOXE AXD JOINT TUBERCULOSIS 87 is : That in attempting the use of any one of these methods, we have neglected to study its mode of action and have looked upon it in the nature- of a " cure-all." We have so far failed most hopelessly in the recognition of the multi- plicity of processes that constitute a joint tuberculosis with discharging sinuses. We know that the underlying cause is the tubercle bacilli but the condition ceases to be a purely tubercular inn animation as soon as there is destruction of the joint lining, with affection of the bone substance. We have now to deal with a changed structure, which has its bearing upon the mechanism of the joint involved and The profession . . ,. , , has overlooked which is quite apart irom the tubercular process. In other the multiplicity words, any agent, however marvelous in its action, if it n v p r j c e e d sse were to remove the affection completely and at once, would in bone ni 11 c i / TIT- tuberculosis. still leave the problem 01 deformity unsolved. is it just to condemn such a therapeutic agent, because in remov- ing the infection it failed to restore the function of the joint ? And still that is just what is being done in failing to adopt any one of the above mentioned methods of dealing with tubercular joints or bones; and so long as we persist The elements in discarding all therapeutic measures which do not accom- formation of * plish a complete cure all at once, so long will we fail in our tuberculosis treatment of these cripples. Such a therapeutic agent will bones are: never be discovered, for it aims at the accomplishment of diversely different objects. But on the other hand, if we recognize the complexity of the processes involved, and the nature of each of these processes, we shall realize at once how near at hand is the complete cure of nearly every case. Let us consider the various processes involved in tuber- t . Anemia. culosis of a ioint. First and foremost, we have anemia of T , h ' dlsease ' ot bone does the part involved. This anemia is responsible in most part t <=*"? for the chronicity of the process and nothing that requires the natural circulatory system for its therapeutic effect can be of any hy P erer value unless this is corrected. Hence, in this condition, disease of tuberculin depends for its favorable effect upon the focal 88 TUBERCULIN AND VACCINE hyperemia that it produces far more than upon the immune response it calls forth. (See Fig. 25.) It may be that the patient already has sufficient immune response and the failure of the circulation to bring the products of this response to the point of infection has been responsible for the progress of the disease. So it happens that Bier's hyper- emia has cured a great many of these cases, by increasing the circulation in the affected joint and permitting the patient's own Antibodies to get to the point of the infection. 2. Mixed Mixed infection is responsible for the continuation of infection. This may the local condition over a period of years, even though the JSlprew, tubercular process itself has long since disappeared from after the ^ Q j^^ condition. Therefore in cases where the mixed causative has been infection is the predominant process vaccines have proved remTvTd. SUCCGSsful. (See Fig. 14.) 3 . serous ac- Long sinuses and bone cavities will heal irregularly when they show a tendency to heal, enclosing infected mate- best of rial between the healed areas which may stay quiescent for the growth ' a a while, but finally must get an outlet and therefore sup- purate, producing a recurrence of what was supposedly encouraged a cured case. This represents a condition where the infection reach of the being tubercular, or mixed, has ceased ,to be a factor in the continuation of the process. The accumulation of irri- mechanism of the tating materials in these cavities and sinuses continues their existence. Filling |these sinuses land cavities with bismuth paste prevents such accumulation and at the same 4. irregular time causes a universal contraction of tissues upon this for- when* e ^S n substance, producing complete healing. But even spontaneous Beck warns against the use of bismuth paste where there healing . . once sets in, is an active inflammatory process present ; for here the-main Irregularly. cause of the condition is a virulent bacteria, and not the causing the mechanical structure. encysting of _, . irritating Ihe placing of an early infected joint at rest will make d"schl? B V 0ry a spontaneous cure possible wherever there is a tendency for such a cure, hence manv of these patients have been cured which finally , ' recurrence. ov orthopedic appliances alone. FIG. 25 The amputation in this case was not an operation for an emergency. Would it pot have been more rational to have localized the lesion by a course of tuberculin treatment before the amputation? That tuberculin would have localized the lesion in this case is beyond doubt, for it has since demonstrated its ability to do so in this case. The patient, a ten-year-old boy, had a negative family history. He was taken ill with tuberculosis of the ankle when two and one-half years of age. After four years of ailment, two years of which he spent in a hospital ward, the foot was amputated. There was prompt extension of the disease into the knee and thigh, the lower third of the femur being involved. He was sent home from the hospital where the ampu- tation was performed, with three discharging sinuses. He was finally admitted to the Home for Crippled Children, in Newark, New Jersey, where tuberculin and bismuth paste treatment was begun in March, 1916. The brace which he had worn was discontinued, and a posterior plaster splint was applied instead. At this writing, one of the sinuses has completely healed, and the other two are about to close. The patient has greatly improved in every way, and it is only a question of a few months before he will be discharged cured. I base this prognosis particularly on the X-ray findings. tuna i'a nsf- it Cftl itt uirrad n -iol noi)8-Hqo HB Jon <3Jrw 9-; no fills ni noijjjji/ijfr- 2. Jfixed vd iioioftl. gd* bfwilfi'joi ovr.rf ol lutioHu-i 'riom infection. nilnoi!JfrJ JfiriT ?noiliiifrqui adJ a-ioled inamtwii niia'/isdi:* io-^-moo This may fefi( j j| , fO j ^ff,;,^ Xmo^ad ei 9[noi9ffoJ rfliv^ tii n has been B ni Jnsqa od rloiiivA IO-KIB^'/; ov/i ,Jn')mIir, lo h'usoy -in..': -rot^A .9v.<; lo noisrwdx!) jqmo-iq // eieitT .bsiBjuqmB BBW Jool orft .\nirn iii 1 removea. lutool 9fiJ lo bij.-lt -ov/ol sift >rfyiiW hire 99n>( ori* it }o 3. Serou -j/fjmr. 9ifi sisifv/ Iiitiqwiti otft fulfil siiioif I B beine ^IfjinA 8B7? sH best of ,^^19-T; 7/M ,jfi/57/-jX iri ,no-iMir{' ) bsIqqi'iO lo't omolT -jrft oJ beJtinib/; culture r ,daicH. fli Hi^id 6w ifl'irnJB'rff -ji^uq rfiu/ti-.iil ftrrc ni! .odw ioh9ioq B bite ,b9finiiuo-jai[i >).' ii'in-w bkd orl rioirf//- -tOBid 9iIT .0161 is const? aoaiinifi 9fft lo erio ,^niii-iv/ ^idJ iA .broi*;ai boilqqB ^i;// iiiHq^ ; trdq encourai qdT .9aolo oi Jirodn O'u; crwt -torfto oib'bnK .! afr.od vbtofqmoo asd beyond 5 O R() itaaup ^laa' si Ji bmi WN -fi97 cii bevo-iqmi vrir;9'ig EBd JnaiJBq .fcitioji^o-iq eid^ 9tifcd 1 .Imuo bo^iBdo'-fli -id Hi/, si! 'ri^Vjd iliiioar v^-i't n mechair .-'.;!. if. nil | of the afflicted , OX ;j,teilCe. . ~?,j - ; h |n^.tc prevents sv- ;-. -<;z 4- *"* healing When spontar healing once se it does irregul. causing encysti irritati inflamr discha cause which ,i> recurr. FIG. 25. THE EFFECT OF THE REMOVAL OF A LOCAL LESION IN A CONSTI- TUTIONAL DISEASE. AND JOIXT TUBERCULOSIS 89 If it were within our ability to discern the predominant process in each case, we could apply these various thera- peutic methods singly with [success. However, the principal cause of the neglect of these methods was the failure to judge correctly the predominant condition present in every case. So that these various therapeutic agents were wrongly applied and, of course, were rapidly discarded. Why not s- Deformity. o i Orthopedic apply them all in every case f feurely the vaccine will not appliances interfere with the action of the bismuth paste; nor will f re essential to limit tuberculin interfere with vaccine treatment; nor will im- functional f .-.-. . destruction munization interfere with vaccine treatment; nor will im- to a minimum, munization interfere with the proper use of orthopedic f rthe rest"* 1 ' appliances. Each one of these therapeutic measures men- the part tioned above and which will be described in further detail during the later on serves its own purpose and fortunately does not *"^^. interfere with one another. ,Their combined use will lead to greater results which will not only help the victim, but also those who fall within the sphere of his influence. Then , , ,, ,. , . , . , The combined only snail we remove irom the patient the consciousness 01 therapy is disease and open the wider field of employment to him. We the . only rational shall remove from his mind the fear of transmission of the treatment disease to posterity, and in a great many instances remove combination the barrier to matrimony. And lastly, but not least, is the o pathological . i . processes. fact that in the case of a patient cured by tuberculin, the orthopedist will be able to decide the exact time for the removal of the various appliances. This necessarily always had to be a matter of guess, as the orthopedist was never certain whether the joint is merely quiescent or cured, and therefore frequently insisted on prolonging the wearing of these appliances for a number of years, even though the patient seemed entirely well. With the danger of a relight- ing of the infection removed the element of guess is elim- inated and both the patient and the orthopedist need not fear the removal of the appliances. 90 TUBERCULIN AND VACCINE General Hypersusceptibility The degree of J n the tuberculin treatment of bone and joint tubercu- hypertus- losis, we have two main varieties of processes to recognize. closed variety, where the tubercular process is limited bone and joint dJ$ aiH .8ifi9^ o'/tavH to ^od /: . / .dilad boog ni 91B rreiblida wdJo gvft baa loddom atH .aisolno -dqib briB ravel tehfiOR t tnol lo 9^/t orfi ifi d^I/oo-^niqoorfw Lad mtjjod 9ri i9j;I aiftnom xi8 .89iio idgin Jjcrf od bnB ,qid dl9f adi ni b'jqo fcniibif.viiq Jna'i^Tlib 9vft ^d biB9iJ e/iw edinom oaidi 10! bun qrnif o) IBOY, 9no -{Ifnnit fiJm; ,.9i9 ,ani i jih3Hi ai^Bmiwrit-itrffl ,ain9mirtil iiiv'n fij no suifl9we bae aicq boqoI^voJb 4 ,i!iiiV/9>^ ai ,09iblidO. boIqqhO 10! 9uioll sdj oJ iiixoo uilH9i9dui ilof lo sigon^Bib B 9T9H Jnomtjsoii -iol ,-, 9TDV/ eoonuilqqB oibeqodHo luogrr sdT .bBm BW Jnioj; iol ineuii-inqftCI .1 .O sdi HI benniiaoa BBW dn-jm!iwi.i hid bns fj'jvlovni qid dlsl 9di diiw IVIBW iif) oj boDiaibB nadl BBV/ oil .iB9V :)no b9(fqqB at// aoifta&hca ^'iJoutl .^foajjlo'iq gniTBdoib 9[jJnB idgii od.t bnB sdt vnnuCI .e^niR9ib Y" 1 ^ diiw bo^ c ):J> ^>;// 9l>lrtB edi bnB qhf arfj oi -798 .4-IUI gaiitrf) qid 9dJ no bsni'iol ^^ft9Dgdrj bloo nilnjmdut gmii 9d^ iA. .9l>Inft ilol edi no I " bnn qid gdi no 898nnia iuol Qili ,5rOI .igdoJ-jQ ni ,( Rnoiio9J_ni dtj;mifl .^I9iiloiq gai^tjiiibBJB Hi Y.d ft^dulino no qo ew iineituq 9)(T . T ^W99v/ horuii ooirii novig OT ni nv/ode ^i noiiibnoo bgluod sdJ lo dqra*jotoriq A .0[fi[ ,82 viBmda''] .c)K!I ,d9TnM ni ao^Rt RI;// dofdw ,62 .jji'-I inol ,IJCI owT -xloaul sdi lo IB19 FIG. 27. FIG. 28 is AN X-RAY PHOTOGRAPH OF THE PATIENT SHOWN IN FIG. 27 AND SHOWS THE TOTAL DESTRUCTION OF THE HlP JOINT WITH SINUSES EXTENDING INTO IT. PIG. 29 SHOWS THE SAME PATIENT AS ix FIGS. 27 IXD 28 AND SHOWS A COMPLETE CURE. Patient, a boy eight years old. Family history negative. In May, 1914, pain and swelling developed in the right ankle, and in spite of wet dressings and an incision, which evacuated large quan- tities of pus, pain was incessant for fifteen weeks, the child screaming day and night most of the time. By this time the left hip became sen- sitive. Until August, 1915, he was treated in the 0. P. Department of the Home for Crippled Children, in Newark, New Jersey. But his suffering became so intense that on that date he was admitted to the hospital ward. Buck's extension was applied to the left leg, and dry dressings to the right ankle, which was discharging a very offensive pus from four sinuses. On October 14, 1915, tuberculin treatment (my method) was begun by Doctor Sidney A. Twinch, of Newark. On November 11, 1915, a fluctuation over the outer aspect of the thigh threatened to break and was incised by Doctor Twinch. Two weeks later bismuth paste in- jections were begun and .administered twice weekly, both in the left hip and in the right ankle. After a few bismuth paste injections in the right ankle, the astragalus came away through one of the sinuses. All sinuses closed in December, 1915. One of them reopened two weeks later but finally closed again. There was an immediate response to tuberculin treatment, in this case the child improving in weight and strength, and requiring but a comparatively short bismuth paste treat- ment to close all the sinuses. Fio. 3( OP, .oil .bio fiiTB ,9f>Iirr, jdh 9dJ ni ! baa nh>q ,MOI ,7fil/: nl -rrnup :yijil bolnnojivo ihiif'ff t rroi i jfii n;; bin; ' i'w to oiicj-: m "iii/m/m* blida 9(fi ^ilaow ne^i^ -roi ir Pfj lo RoiiiJ -i:ia omrmil qrtf Jlaf otf* arnit Bitfi vfl .'irrrij orfJ lo .j^om irf^in brrr, x*i> In In-.mtn.qofI .4 .O orft ni JwlBO'id SBW oil ,fJ(!I ,tsifguA liinU .oviiig if ju.'i .V'jrt'ioT. v/o/1 t >hi>7/9/I ni ,n9il)lhf'j I.ioIqqhO 10! arnoll orii iff! ot iwttimbn >-.BV/ aif sJsh iurfi no dBifi aenaJni oa orneoaff v/ib firm ,^ol Jlol 9fft ot fwilqqu efi^ff noJHrroi/o g'vIouS .binw - i9v n gnigifirfoaM) auw riahlw t 9[yins iif^i-x 9dJ oi ^ rni> tuo'i mail auq (borfJom ^m) InemJcg'iJ nifiJOTodui ( 5iOI ,I igdoioO nO f iodffio7o>I nO .>I-rriWf)V; }o t fbrriv/T .A {gnbig oj fi9(f9ifi9'ir(J dtrfi 9rW lo ioaq^B isJuo odJ 1970 -iu oJ/:q rilnmaM -ig^^f ?.^99W owT .ifoniwT loiooCT ytf tlof 9(it m tfiod ,7^997^ 9317^1 b9'i9J^iniffibj5 brtr, ni ftnuijo r )j.(ri 9ier,q dtrrmsrcf 7/9! B i^\L .gfjlni: iifgi-i 9ifi ni bnc qiil .S9=ri(iiy idJ io 9no dr;oidi ^nv/e 9rar.9 ftrrfr;ii/nia 9di ,sl~AnR Jdgi'i edt 'ib-jv/ 07/J I)9ii9qo9T raeifi lo 9nO .5101 t 'i9daio-joCI rri I.o^ob E9eonis [!A ot oauoqeoT 9iBtf9mmi B ssw oioifT i.ur td^i97/ ni wnmyiqrnr DHda ed^ 98B9 ardt ni ^; -q dtrrriT-.id j-ioilz vfovHmfiqmoo B ind j>nhii/p9i bns , gdJ Ifu geola oJ FIG. 30. FIG. 31. SAME PATIENT AS FIG. 30. This X-ray of the hip taken after bismuth injection shows the long sinuses. The stereopticon X-ray reveals the sinus going clear around the hip joint. It could be seen at a glance that any attempt at spontaneous healing would have rendered irregular healing and encyst- ing of parts of the sinuses extremely liable, with consequent recurrence. This was prevented by bismuth paste injections. FIG. 32 This patient, a boy nine years old, has a negative family history. When he was eight months old, the baby carriage in which he was sleeping fell down a flight of stone steps. After this his legs always seemed sensitive on handling, but he was given no treatment. At one year of age he walked, and neither limped nor showed any signs of pain for six months. Then the left hip became painful. The tubercular nature of the condition, however, was not discovered until April, 1911, when he was brought to the Home for Crippled Children, Newark, New Jersey, after three years of ailment. A plaster spica was applied to the left hip, but the condition became ,so acute that in less than two weeks he was admitted to the hospital ward, with Buck's extension replacing the plaster spica. During the following few months abscesses with resulting sinuses developed all around the hip and thigh. During the following year the abdomen began to grow very large, with the development of distinct signs of tubercular peritonitis. When the author first saw this patient in October, 1915, the boy had not left his bed in the hospital since April, 1911. Five or six fistulous openings around the hip and thigh oozed a thick creamy pus. The abdomen was greatly distended with the liver and spleen reaching down to the brim of the pelvis. This case illustrates an extent of the tubercular process which was beyond the control of the surgeon, and what is more serious, it seemed beyond the reach of the patient's healing powers. The promptness with which this patient responded to the tuberculin treatment leaves no room for doubt as to the efficacy of tuberculin in tubercular affections. The X-ray photograph of this patient (Fig. 33) shows the extent of, the tubercular process in the hip; and Fig. 34 shows the same patient cured, fifteen months after the beginning of tuberculin treatment. S8 .oil .TjioJaid xl' rac l gviiBgen B ssrf ,blo 8t/!9^ 9nin ^jod a .Jraiifiq eirfT BB7/ 9if rioidw ni 9BhiB9 ^d/?d ->di nc t f)9^Ii577 oil 9B io IBST. 9no odT .lolaraq om/3D9cf qid *l9l 9dJ uodT .edtaora zia toi nieq io liiau jVnsvootsif) ion eaw di lo odT .aiowoq giiilr,'.,! ' Imitfiq 9dJ i on 89VB9I iiramifio'ij nifjjoiodui edJ oJ hobrioq,-')-! ineiieq airii doidw .^noiJogTlB irdii-jiodr/i ni nilrwr^dut lo ^or.offls sdi o) %ji id.iob 10! moot Jo Jnelxa 9dJ eworia (88 :i1) Jngiijiq sidi io dqBT^oJodq ^Bi-X 9dT inoitcq omse adt awjda 4-8 .gil bnc :qid edi ni eg99Oiq iBFu9T9daJ edJ lo FIG. 32. FIG. 33. X-RAY PHOTOGRAPH OF THE SAME PATIENT AS FIG. 32, SHOWING THE SINUSES FILLED WITH BISMUTH PASTE NOTE THE ALMOST COMPLETE DESTRUCTION OF THE HIP JOINT. FIG. 34. SHOWS THE HEALED CONDITION OF THE SAME PATIENT AS FIG. 32 ALL THE SINUSES CLOSED, THE SPLEEN BARELY FELT BELOW THE MARGIN OF THE RIBS, THE LIVER ONLY Two INCHES BELOW, THE ABDOMEN FLACCID, THE BOY TO ALL APPEARANCES IN PERFECT HEALTH. REXAL TUBERCULOSIS 97 the cases where there is no benefit to the patient or where there is extension of the disease following the removal of the kidney, that the operation cannot be called a success. As to the complicated mechanism of the organs involved : It is well known ,that the treatment of any part of the genito- The urogenitai .. . , -. , . . tract is so urinary tract is very difficult and complicated, no matter complicated what the cause of the pathological process, may be. We all thatltu**' know how prone to chronicity is any condition arising in easily sus - 1 -i n ' -i e .'*' ceptible to the kidney or in any other part 01 the genito-urinary tract, permanent When a posterior urethritis remains for years, it is not damage - because the infection with the gonococcus differs from the infection with any other organism, for, when the colon bacil- lus produces a pathological process in the pelvis of the kidney, it is equally tenacious. Even the non-infectious diseases attacking the kidney leave permanent damage be- hind. We need only recall nephritis complicating scarlet fever, or diseases causing an interstitial connective tissue change as in an interstitial nephritis, to realize how sus- ceptible to damage the kidneys are. It is the complicated mechanism of the genito-urinary tract that renders it vul- nerable, not the nature of the process attacking it. Hence, permanent damage depends less upon the virulence of the process than upon the Jength of time such process is allowed to go on without being checked. It therefore follows that in renal tuberculosis, the proper treatment must be instituted as early as possible and that many symptoms persisting beyond such treatment are due to the permanent damage done before treatment rather than to the persistence in spite of the treatment of the original pathological process. The early treatment of renal tuberculosis naturally de- pends upon the early diagnosis of the condition. But just here the greatest difficulty arises. Early tubercular pro- cesses are usually circumscribed, very slow in progress, and thus exercise very little influence upon the function of the kidney. The patients at this time are usually in robust health 7 1)8 TUBKKCULIN AND VACCINE To obtain ideal results with tuberculin it must be applied before permanent damage has resulted. But just here we meet with the greatest difficulty, as an early diagnosis is rarely made. and merely go to the family physician complaining of an annoyance, which usually consists of frequent micturation, especially at night. The possibility of a tubercular affection in the kidney is remote from the physician's mind. Every conceivable condition that might occur in the bladder, urethra or prostate is suspected, and the patient treated for it. If, for instance, the male patient gives a history of a gonorrheal urethritis, then, of course, the symptoms are easily explained on those grounds and the patient is subjected- to all sorts of instrumentation and treatment. With the progress of the disease, the diagnosis of cystitis is made and is followed by irrigation of the bladder, prostatic massage (encouraging an active lesion in the prostate if a tubercular infection has reached it) and various other means directed, against a sup- posed gonorrheal infection. When the process is still fur- ther advanced, the symptoms referable to the kidneys begin to be more pronounced; pus in the urine, perhaps blood in the urine, backache radiating toward the pelvis; all these symptoms bring the diagnosis of renal calculus, and in the female many pelvic (disorders are suspected. Finally, the diagnosis of renal tuberculosis is made, sometimes by a careful study of the patient through expert assistance, some- times by chance as in the case mentioned in connection with mixed infection (page 163), where the diagnosis of tuber- culosis was made upon the discovery of tubercle bacilli in the thick pus, which took the place of urine. Occasionally, the X-ray finds an enlarged kidney without calculus and raises the suspicion of tuberculosis. To sum up ? the diagnosis of renal tuberculosis always conies too late for the institution of early treatment prin- cipally for the reason that the usual methods for making a diagnosis are complicated and generally require a spe- cialist. The result is that the general practitioner tries all available treatment for any other possible disease until he finds his treatment hopeless and refers the patients for expert advice. The diagnosis of renal tuberculosis by means REXAL TUBERCULOSIS 99 of tuberculin -is bu far the best at our disposal, for it is the w ' ththe subcutaneous only means for early diagnosis. ^Yith tuberculin, diag- tuberculin test . . an early nosis can be resorted to by every physician and in every diagnosis is locality. The interpretation of the positive finding is simple ne^oni to in the case of renal tuberculosis and if the multiple method be properly applied and of tuberculin inoculation is practiced (see page 23), it is correctly devoid of danger. Frequent micturation in an otherwise inter P reted - healthy individual should always be the subject of sus- picion and a tuberculin test resorted to at once. If the case is not tubercular, the tuberculin will do no harm. If the case is tubercular, the harm done by a constitutional reaction, even if severe, can not be considered in compari- son to the harm that comes to the patient from long delayed diagnosis and from instrumentation, bladder irrigation and other treatments that are resorted to, previous to the diagno- sis, either for the treatment of supposed conditions, or for the diagnosis itself. It is quite true that were we to suspect a tubercular condition in every case where a definite diag- nosis cannot be established, and where the patient com- plained of frequent micturation, the vast majority of patients will prove negative to the tuberculin test. I have never yet found a patient resenting the test when it proved negative and when it was explained that through the test we have excluded even the remotest possibility of an active tubercular affection. On the contrary, the patient is grate- ful to the physician for his endeavor to establish an early diagnosis of a suspected condition. With an early diagnosis established, how shall we O nceanear/y proceed with the treatment? I do not know of any one diagnosis is , . . , made, no who would advocate the removal of a kidney with an other remedy earlv lesion. There remains onlv the hvgienic-dietetic- ca "P rove . ' e effective in and-climatic treatment to be instituted for the patient limiting the when an early diagnosis is made. And what can that offer we ii e a s s s us? Unlike the patients with pulmonary tuberculosis, this ^e^urce* class of patients are in fine physical condition, and if a of infection fine physical condition did not prevent the lesion from tuberculin. 100 TUBERCULIN AND VACCINE starting in the kidney, how can we expect treatment which depends upon the improvement of the physical condition, to cure or even check the disease ? Here we deal with a com- bination of circumstances all of which are already favorable to the production of a natural immune response against the tubercle bacilli, except that the mechanism producing the immune response is faulty. The stimulation of this mechan- ism with tuberculin remains the only logical early treat- ment. All other resources necessary for the patient's own defense are present in sufficient quality and quantity. By the time When once a diagnosis is possible without tuberculin, the patient presents a picture of chronic inflammation that made under ordinary T1O O th er chronic condition presents. Especially is this true methods, . f . permanent in the male patient. He is never free from pain and dis- ah-T^dy a comfort, cannot have a peaceful night's sleep on account of the necessity of frequent urination, often cannot do without a permanent urinal, because of incontinence; cannot take a ride in any vehicle because the jars cause agonizing pains ; in short, the advanced renal case is subject to every con- ceivable discomfort that makes life unbearable. Most of these symptoms come from the extension of the disease into the bladder, the prostate and the urethra. A great many small ulcerations which have been produced traumatically by instrumentation form the seat for new tubercular infection. Although no one but the skilled specialist should resort to cystoscopy and ureteral catheterization, they are nevertheless far too frequently resorted to. Many of these instrumental examinations are made in spite of the knowledge that they could in no way improve the condition of the patient, but which, on the contrary, may aggravate the condition temporarily or even permanently. In the exclusive interest of the patient, what would seem to offer the best procedure in the treatment of renal tuberculosis in the state in which it is discovered in the majority of instances? It is quite true that a removal of a kidney has occasionally cured a case of renal tuberculosis, TUBERCULOSIS 101 even with ulcerations of the bladder. I am quite certain that in these instances a closer analysis would reveal that the principal cause of the patient's condition at the time of operation lay elsewhere than in the tubercular infection. For example: In a case of renal tuberculosis where the tubercular infection is more or less spent, but where the ulcerations in the bladder and the predominating patho- logical processes in the kidney are due to mixed infection, the kidney will act as a foreign body. The stroma is entirely destroyed iby multiple abscesses so that the re- moval of the kidney is sufficient to cure the patient. Again in a case of calculus with accompanying hematuria or pyelitis producing the predominant symptoms but where a small quiescent tubercular lesion exists, the removal of such a kidney will result in a complete cure. This is ana- logous to the condition that exists in bone and joint disease where the tubercular infection has healed and the sinuses are kept open by mixed infection or irritating accumulations, the removal of which by bismuth paste is sufficient to com- plete the cure. On the other hand, in the majority of cases where the The removal principal cause of all the symptoms is a slowly progressive s inmost tubercular infection, how can we expect to cure the patient instancesan attempt to with the extirpation of one kidney ? Not only do we leave remove a local behind a tubercular process in the urinary tract below the constitutional removed kidney, but with the added burden suddenly thrown disease - upon the remaining kidney, its resistance may be momen- tarily lowered and it may become infected from the original focus. The hypersusceptibility being increased as a result of the operation, will more than encourage this occurrence and bring about a most hopeless condition. General Hypersusceptibility The general hypersusceptibility in renal tuberculosis is on a par with the general hypersusceptibility in closed glands so long as the infection- is limited to the lesion in the kidney. 102 TUBERCULIN AND VACCINE The general That [ s ft i s no t of a very high degree and would require hypersus- ceptibiiity in about 0.10 c.c. of the second dilution to cause a reaction. There are, of course, a great many exceptions, such as the tuberculosis is of a 1 degree. hypersuscep'tibility in early cases of renal tuberculosis fol- lowing an infectious disease or in oases where the focus of the infection is active, in which instance we would consider the hypersusceptibility due to that focus and not to the lesion in the kidney. In later cases, there are two (distinct grades of hyper- susceptibility. On the one hand there is the class of cases with extensive ulcerations of the kidney, with complicated The general bladder ulcerations. In these cases the lesion is active, the ceptTbufty in susceptibility is extremely high and occasionally will require advanced cases a s i x th dilution for the beginning of treatment in order to is of two distinct grades: avoid reaction. On the other hand, we have renal tuber- wVere 'there culosis consisting of calicies, which are converted into sacks is an active O f c heesy material or cold abscesses. Here the entire kidney ulcerative * ..." process in acts as a foreign body, its function being entirely destroyed. and Madder. ^ ^ s a pt to have ,very little active tubercular inflammation it is low in j n j^ TI^ tubercle bacilli that are still found in the urine cheesy or fibrous kid- are of a fungoid character, while the ulceration in the blad- "hep'roceYs" c ^ er an ^ elsewhere is continued merely by the presence of is continued the ac jd urine and mixed infections. In such a condition, by mixed infection and the patient is apt to be in good physical condition with very baciin. " little loss of weight, in spite of the ever-present extreme dis- comforts. The susceptibility in these cases is very low and occasionally does not exist at all. The latter is the condition in which the removal of the kidney without any other treatment [very frequently cures the patient. The presence of hypersusceptibility in various degrees and its absence altogether in renal tuberculosis may be of service to the surgeon in determining upon a nephrectomy. For instance, if with a tuberculin test a considerable degree of hypersusceptibility is discovered, before a contemplated operation, it may serve as a warning against it and a course of tuberculin inoculations should be' given instead, or pre- RENAL TUBERCULOSIS 103 paratory to the operation. On the other hand, if the hyper- The tuberculin susceptibility does not exist at all, or only to a very mild guide to degree, it is sufficient evidence that the tubercular infection -interference, has subsided and that the condition in the kidney and else- where is merely the result of the tubercular infection. Then surgical interference can be instituted with a fair degree of safety, and a reasonable amount of success may be expected. Beginning Treatment In early cases of renal tuberculosis, it is quite safe to begin treatment with the fourth dilution, and when it re- quired the second dilution to cause a reaction during a test, it is safe to begin the treatment with the third dilution. In more advanced cases our judgment as to the amount of tuberculin in the beginning of treatment must be influ- The beginning enced by the nature of the symptoms at hand. Thus, if the tuberculin 1 patient runs an abnormal temperature, for which no other should wait ' until an cause can be found than the tubercular process, the fifth acute mixed dilution is indicated for the beginning of the treatment. ^ controlled. That is also true in a case of persistent hemorrhage. How- ever, if the severer symptoms are caused by other conditions than the tubercular process conditions such as calculus, mixed infection, pyelitis, etc. tuberculin treatment can be instituted with the fourth dilution. It is, however, better to treat the mixed infection until the temperature is normal (see page 175) before tuberculin treatment is commenced. Conclusion of Treatment The conclusion of treatment as far as tuberculin is con- in most cases cerned is more like that in a case of pulmonary tuberculosis with L stimulation of means 01 saving the lives 01 many who had insufficient the immune immune response to begin with. By way of illustration, s p nse is I shall mention one recent report. It came from the Loomis most rational Sanitarium and was made by Doctor H. , M. King, an^t"" 4 The report showed that in spite of sanitarium treatment earlierinth disease it is under the best posible conditions, over twenty-nine per cent, applied the of the incipient cases treated at that sanitarium died of a response, and recurrence of their disease within ten years after discharge. the less permanent Many such reports can be found throughout the literature; damage very few, however, could show even such favorable results. In contrast, if we examine into the results of immuno- therapy in incipient cases of tuberculosis reported, we shall find that the percentage of permanent cures runs close to one hundred per cent., and this from unquestionable authority. The difference can easily be explained: the hygienic-dietetic measure is one that aims to strengthen the individual as a whole with the hope that it will also increase his natural defense against tuberculosis as an infection. In a large number of incipient cases nearly seventy per cent. it succeeds. But even in these the hypersuscepti- 108 TUBERCULIN AND VACCINE The artificial stimulation of the immune response does not interfere with the natural immune response. There are no real contra- indications to the use of tuberculin. Fever may be a temporary contra- indication when caused by mixed infection. bility remains; and, while in the thirty per cent, of fatal cases it was the means of an early recurrence and death, in the favorable cases it still remains a menace even beyond ten years. The artificial stimulation of the immune response can- not interfere with the natural immune response. That is beyond question. Where, then, is the objection to the use of tuberculin in such cases that would have gotten well on the hygienic-dietetic treatment alone ? The only danger lies in the too frequent and in the severe reactions caused by a faulty technique. The fault, therefore, is not in the tuberculin itself, but in its method of use, and once we have established a method of administration which avoids severe and frequent reactions, the objection to tuberculin, per se, can no longer be advanced as a justification for its neglect. Centra-indications From the outset I want to be understood as denying the existence of contra-indications. I do not believe that real, genuine contra-indications to the use of tuberculin exist. The harmful results recorded were not obtained by the use of tuberculin under the wrong conditions, but from the wrong method of use of tuberculin; ;and the failure to recognize this fact has produced a long list of " contra-indications." Were we to take a census of the conditions put forth by different investigators as '" contra-indications " to the use of tuberculin and take them all seriously, there would be very few cases left for tuberculin therapy. For instance: FEVER is maintained to be a most constant contra-indi- cation in spite of the fact that it is very frequently a symp- tom of incipient tuberculosis where tuberculin has its most effective field. However, as mentioned above, fever may be produced by mixed infection. The failure to differentiate between this fever and that produced by the tubercular infec- tion has occasionally led to an improper application of the tuberculin treatment, producing harmful results in cases of PULMONARY TUBERCULOSIS 109 fever. There is no antipyretic as effectual as tuberculin in tubercular fever. The fever produced by mixed infection should not exclude the use of tuberculin altogether ; it should postpone its use until the mixed infection has been cleared to the extent of reducing the temperature. However, if the mixed infection resists all treatment, and the fever which it . causes continues ithe wasting of the patient, tuberculin will have no effect. 1 DEBILITY. Debility is another " centra-indication " very frequently mentioned. As stated above, the loss of reactive properties on the part of the patient forms a natural Debility is a limitation and not a centra-indication to the use of tuber- limitation culin. It is true that the use of tuberculin in cases Indication*" suffering from debility will produce absolutely no results, but neither will it cause any harm. And since we cannot determine absolutely, until the tuberculin has been tried, whether or not the reactive properties of an individual are lost, the use of [tuberculin will occasionally meet with a re- sponse where the symptoms of debility were pronounced. Thus, by excluding tuberculin from a whole class of cases, we might omit the use of tuberculin where it would prove of inestimable value. True, the number of such cases is very small, but it is Theuseof tuberculin is also true that trying tuberculin for a short time in cases justifiable in where the immune response has been exhausted will pro- ^ It can pro- '* duce no harm, as a reaction cannot occur. In the practice ducenoharm. of medicine, it is axiomatic that the use of a remedy is* justifiable in many cases where it produces no beneficial results, but proves harmless so long as that remedy is efficient in the salvation of the few. That tuberculin might awaken an immune response is Tuberculin "', * : i 11- may awakcn particularly true in those cases of cachectic tuberculosis a response in with only small areas of lung involvement. We know that the effect of tuberculin on the blood is distinctly stimulat- ing, both the red and the white blood cells increase far thought to more rapidly than through any other form of treatment 110 TUBERCULIN AND VACCINE Classification The classification of pulmonary tuberculosis is by no means an easy matter and it is not surprising that almost i. incipient. as .many varieties of classifications exist as there are writers siowiy on the subject. The structure of the lung tissue, the variety Progressive: j n tne pathological process, to which added the great dif- (a) fibrous . . phthisis; ference in individual susceptibility and resistance to the indukerl'ti've 3 tubercle bacilli, all taken together tend to make for not only 3 Acute or a variety in the gross pathological difference, but also in (a) febrile; the symptoms which they bring about. Fortunately, the task ( infeTtion d is not quite so difficult for the immunizator. In dealing ( 2 ) auto- w j t jj t j le i mimme response, we need take cognizance of the inoculation; (b)a{ebriie; pathological difference in the lungs of different individuals rhag'cT 011 l v i n as f ar as tne J produce a difference in symptoms and en traumatic, t j iat on ] v j n a p- enera l wa v. As far as tuberculin therapy (2) ulcerative. is concerned, only such differences can have any bearing upon it. as the presence or absence of hemorrhage, or the chronicity or the rapidity of the process involved. This classification therefore will depend entirely upon its refer- ence to tuberculin therapy and if it differs materially from the usual classifications bearing on the stages of the disease, etc., it will find its justification in the fact that this classification is merely made to add to the simplicity of the tuberculin therapy. Accordingly, the tubercular pro- cesses in the lung are divided into 'the following three groups : 1. THE INCIPIENT PULMONARY TUBERCULOSIS. Under this group only such cases are considered which require a test to establish a diagnosis and which show physical signs before the presence of tubercle bacilli in the sputum. 2. TlIE CHRONIC OR SLOWLY PROGRESSIVE PULMONARY TUBERCULOSIS. Under this group are included the type of cases which persist for a long time, the natural resistance being sufficient to prevent an acute attack, but not quite sufficient to arrest the process; also those cases in which the process has been arrested one or more times with the light- PULMONARY TUBERCULOSIS 111 ing up of the infection under a change of conditions whether extrinsic or intrinsic. All patients with tubercle bacilli in the sputum are here included, embracing all cases, from local- ized infiltrations in the lung to those that have progressed for several years, and are now suffering from ulceration and cavity formation or calcification. For the purpose of greater simplicity, this group is subdivided into two types. (a) Those with extensive infiltration, connective tissue change or fibrous phthisis. (b) Those with calcification process, the calcarious de- posit finally causing ulcerations and cavity formation. We shall not discuss here whether the action of the calcarious deposit as a foreign body is brought about by mixed infec- tion or by the tubercular process, as this question has no bearing upon tuberculin therapy. But the decision as to whether there is a fibrous phthisis or cavity formation will have a great bearing upon the conclusion of treatment as will be indicated further. 3. ACUTE OR ACTIVE PULMONARY TUBERCULOSIS. Here we shall include the more active form of tuberculosis, the kind that progresses rapidly either through lack of the immune response or through an over stimulation of the mechanism of immunity .by auto-inoculation, or through a rapid loss of strength, due to an excessive loss of blood. In this group belong the greater number of patients who are considered as disqualified for tuberculin therapy, and at the same time stand particularly in need of something more than the present day treatment to turn the tide in their favor. By a closer analysis we are isure to be able to find a considerable number of those considered hopeless that may be rescued with tuberculin. With a safer technique, 'any harm that might be caused by tuberculin is so slight and so infrequent that the good its general use can accomplish in saving the victims of this disease will far outbalance any possible harm. Thus, we shall find that an active condition and pyrexia are brought about not so much by an uncon- 112 TUBERCULIN AND VACCINE The structure of pulmonary tissue, with its rich blood supply encourages autoinoculation which increases the hypersus- ceptibility. trolled tubercular process as by a mixed infection, and if we were to take fever as a general centra-indication we would lose a large number of cases that come under this class. A subdivision of this class into febrile, afebrile and hemorrhagic cases, enables us tv further simplify treatment. For example, in taking up the first of these three, we must endeavor to analyze the cause of the fever and determine whether it is due to autoinoculation or to mixed infection. In the active afebrile group where the rapidity of the process is causing ulceration, the ,sole cause may be an insufficient immune response. Under the hemorrhagic group, we must take into consideration whether the hemorrhage is due to ulceration in the vicinity of larger blood vessels or whether the hemorrhage is traumatic, brought about by too great exertion when coughing, or by excessive exercise. GENERAL, HYPERSUSCEPTIBILITY. In pulmonary tuber- culosis, as a rule, the general hypersusceptibility is much higher than in other forms of the disease. If we are to accept the theory that tuberculosis of the lung is the ter- tiary form of the disease and that the focus of the infection is in the glands or bones, whether in the immediate neigh- borhood or at a distance, the hypersusceptibility must be high to begin with in order to allow of such extension into the lungs from a quiescent lesion. Again, lung tissue with the blood current running through it in such a perfect net- work invites auto-inoculation far more easily than does any other tissue. This auto-inoculation increases very materially the hypersusceptibility ; so that here again we have a physi- ological paradox as in the case of the mechanism of im- munity. The richness in the circulation tends to quickly overcome the tubercular infection ,when it localizes in the lung, but that very element causes too large a supply of anti- bodies and too ready an absorption of the poisonous proteins which cause the constitutional reaction, allowing at the same time an extension of the process. Thus the hypersuscepti- bility in acute pulmonary tuberculosis is very high. PULMONARY TUBERCULOSIS 113 In the presence of a tubercular lesion in the lung, the hypersusceptibility which accompanies all other tubercular lesions must be considered with reference to the lung lesion. Thus, it may happen that a large beginning dose of tuber- culin may produce disastrous results in an old case of joint tuberculosis with fistulas, where the susceptibility would be low, but jwhere the contrary is true because of an overlooked incipient apical tuberculosis. The third dilution would be safe in the case of joint tuberculosis without the lung lesion, but in the presence of the lung lesion the susceptibility is much higher, requiring a fifth dilution for the beginning treatment. In the case of multiple lesions, we must treat the patient ,with reference to the lesion which is accompanied by the highest degree of hypersusceptibility. Treatment INCIPIENT. As stated above, under the class of inci- pient cases of pulmonary tuberculosis we include ' only those with lesions in the lung which are difficult to detect, requiring, in a great many instances, the tuberculin test to establish a diagnosis. As soon as symptoms arise which define the diagnosis, as tubercle bacilli in the sputum or a Hypersus- hemorrhage, we no longer consider the case incipient It noTso therefore follows that the full amount of susceptibility in the those cases 11-11 nil mi classed here cases coming under this class has not yet developed. They as incipient. usually come to a physician complaining of a " hanging on " cough following a " bad cold," or an acute infection such as influenza, pneumonia, pleurisy, etc. Or, they come complaining of loss of weight, night sweat, lassitude, a gen- eral feeling of fatigue, or a general " run-down " condition, which persists for a while in spite of tonic treatment, good food, etc., until eventually a closer examination reveals a few rales at one or both apexes with perhaps a little dull- ness or increased fremitus. All these signs lead to a tuber- culin test to establish the presence of an active tubercular lesion. The active pathological process has been brought 8 114 TUBERCULIN AND VACCINE Begin treatment in incipient cases with the fourth dilution, except in cases where a diag- nostic test has shown that it may be safe to begin with the third dilution. The conclusion of treatment is very simple. about by the presence of a small amount of hyper sus- ceptibility left over from a previous tubercular process. Whether the previous process existed at the same time and was arrested or whether it existed as an adenitis in infancy or childhood, has no bearing upon the present con- dition. Any pathological process, however mild, forms a temporary traumatic area in the lung and acts as trauma in the etiology of bone lesions by attracting the tubercle bacilli and starting a tubercular process. The area of infec- tion being small, the number of (tubercle bacilli that come into play is as yet limited and as a result the protein poisons have not yet been set free in the circulation in sufficient quantities to increase materially the hypersusceptibility. Beginning Treatment. The tuberculin treatment of incipient pulmonary tuberculosis is very simple. We can begin with the fourth dilution in a great many cases, espe- cially in those cases where more than one test had to be made and where the amount of hypersusceptibility was thus more or less determined. If a fourth or fifth test was required (see page 23) before a constitutional reaction was produced, it is absolutely safe to begin the treatment with the third dilution. Conclusion of Treatment. In the incipient pulmonary tuberculosis, it is rarely necessary to deviate from the usual form of conclusion of treatment as outlined in the " Scheme of Dosage," for in limiting the incipient cases to those con- ditions where the tubercle bacilli" a-re not yet present in the sputum, we have no more difficulty in its treatment than in a simple case of tubercular adenitis. After the conclusion of the series of inoculations with the first dilution of BE, there remains nothing further for us to do for the patient except the periodic tests over a period of two years for the possible return of hypersusceptibility. CHRONIC OR SLOWLY PROGRESSIVE. Among the slowly progressive cases of pulmonary tuberculosis we recognize by far the majority of patients that seek ambulatory treatment. PULMOXABY TUBERCULOSIS .115 A great many of these patients have received more or less of the hygienic dietetic and climatic treatment, have been benefited by it but are now suffering from recurrences ; many The great have gotten disgusted .with this treatment because of the a^uiatorV slow progress they were making toward recovery, have grown P atients with impatient at the length of time they were kept from their tuberculosis families, their occupations or their favorite haunts and have * finally returned to their usual mode of living, taking any risks for the sake of being comfortable while they last progressive. Others return to their homes and occupations from a sana- torium or mountain resort after slight improvement, either under the impression that they are cured, or in spite of tHe advice of the most expert in the profession. The amount of benefit thus gained wears off and they ; are soon found again in the doctor's office, denying emphatically that they are ill enough to go back to the sanatorium, and demanding ambu- latory treatment so that they may continue their occupation. Particulary is this true a.mong active and ambitious indi- Tuberculin 11 _'"" i i mi ls t ' ie n 'y yiduals to whom inaction is worse than tuberculosis. Ihe treatment to enforcement of inaction sometimes hastens the disease in spite of the best treatment and climate. Just such patients patients .,, t> 1-1 T will submit. will give the most gratifying results with tuberculin treat- ment. The usual optimism in the curability of their con- dition, added to the beneficial constitutional effect brought about by being kept at their occupation, go to make a most favorable prognosis for tuberculin treatment. In this group we have cases that cannot stand high altitudes either on account of the heart condition or on account of the existence of a chronic bronchitis, which in many in- stances makes sleeping in the open during cold weather impossible. In every sanatorium are to be found a number of chronic cases with the tubercular condition progressing favorably. The most we can hope for in this class of cases is an arrest of the process. Patients with arrested lesions are returned home, the patient glad to get home and the 116 TUBERCULIN AND VACCINE Tuberculin added to sanatorium treatment would increase the quality and permanency of the results obtained. The relief produced by tuberculin in chronic ulcerative pulmonary tuberculosis calls for its use even in hopeless cases. sanatorium congratulating itself upon obtaining such results. At the same time, it ,is an ever-present fact that of the arrested chronic cases that go back to their previous occu- pations, nearly all recur. Would it not be at least reason- able to have added tuberculin properly administered to the treatment of these patients ;and thus have gained a large degree of immunity against recurrence? Surely the tuber- culin would not have interfered with any other treatment at the sanatorium. No one who ,has used tuberculin exten- sively will now assert that any case which progressed favor- ably through a number of years under the hygienic-dietetic and climatic treatment would have terminated otherwise than favorably if tuberculin had been added to the other treatment. Again, we have the patients in whom the process slowly progressed through a number of years. During this time new areas of infiltration constantly occur during a period of lowered resistance, due to whatever cause, followed by connective tissue change during a period of heightened re- sistance. This see-saw process goes on for years, the advance in the disease never going far enough to kill the patient and the healing process never going far enough to cure the patient, until the time comes when the patient slowly dies of insufficient lung tissue for oxygenation. During any one of these periods of heightened resistance, an artificial boost would be sufficient to accomplish a cure. On the other hand, any preventive measure which would tend to avoid a period of depression would allow the healing process to continue long enough and accomplish the same purpose. Again, we have a class of cases where the tubercular process has gone on to cavity formation with sclerotic changes throughout the lungs, dyspnea, cough and an un- limited amount of expectoration are the principal symp- toms which are constantly present day and night. This process may go on for years before the patient is carried off. In the meantime he is in discomfort and a taenace .to PULMONARY TUBERCULOSIS 117 his surroundings. For in these cases, the number of tubercle bacilli present in the sputum is more abundant than in any other form of the disease. The cavity is filled with the best possible culture media for the tubercle bacilli and the lung forms the best incubator for their growth. These classes of cases are hopeless to begin with and therefore an extensive therapy like tuberculin therapy would seem a waste of time. But that is not the case. Just these cases seem to cry for " relief," and as they will often put it, " or death." A constitutional reaction in these cases will not very frequently Tuberculin occur, in fact, if it does occur, the effect is not at all "* alarming. At the same time, the relief which tuber- tubercle bacilli -i. *ni" i IT *ii i_ from the culm will bring to the patient is so marked, especially when spu tum. augmented by mixed infection vaccines, that it is almost criminal to withhold it. The cough may not be diminished by tuberculin, but its racking will be greatly lessened. The tight feeling in the chest which the patients describe as " a grip which seems to squeeze the breath out of their lungs " will be relieved to a varying extent. It is surprising in how many cases of. this kind, the tubercle bacilli will dis- appear from the sputum, a fact which speaks loudest for tuberculin therapy even in hopeless cases. So that even if we are to ignore comforts ;to a hopeless case during the last months of his life, surely we must remember that we must prevent him from being a menace to his community. Beginning Treatment. Although the chronic cases, whether they have the fibrous or the ulcerative form of the disease, possess a more or less controlled hypersusceptibility, it is best to begin with the fifth dilution of OT and continue in the usual way three or four weeks. If a distinct focal reaction is elicited by every inoculation, especially if ac- co" .panied by a local reaction even if only mild it is best to continue the treatment throughout, according to the scheme outlined in Table I, page 57. On the other hand, if the tuberculin seems to produce no impression on the patient's condition, better results can be obtained by a 118 TUBERCULIN AND VACCINE in the quicker approach to the maximum tolerance. This can be treatment done by increasing the increase at every inoculation, instead wro'Ic to* of increasing the increase at every other inoculation, until the maximum a distinct focal reaction has been elicited by two or three tolerance may . . be advisable successive inoculations. At this point, it would be best to miny'cVses. discontimijB the more rapid increase and return to the usual method of increasing the increase at every other inocula- tion, without waiting for a constitutional reaction. Should a constitutional reaction take place before we have re- duced the rapidity of the increase, the usual indications following the constitutional reaction should be complied with ; i. e., after an interval of one week, resume the inocu- lations with a dose equivalent to the third last, and not only should the increase be reduced to the amount of increase given at the commencement of treatment, but this increase should not be increased more rapidly than at every other inoculation. (Table II, page 59.) From this point, the usual routine of doses is continued. Conclusion of Treatment. The conclusion of treatment in a case of fibrous phthisis does not differ greatly from that required in a case of surgical tuberculosis. In a great many cases the removal of hypersusceptibility with OT would be sufficient to effect a cure as [far as the tubercular infection is concerned. The localized hyperemia brought about by the focal reaction in response to the tuberculin inoculation is sufficient to encourage the already present tendency to scar tissue formation. Since a complete cure in fibrous phthisis is prevented by the tubercular process keeping slightly ahead of the scar tissue formation or healing pro- cess, the slightest (delay in the progress of the infection plus the stimulation of the healing process by the focal reac- tion, makes a cure in this class of cases almost certain. However, since we very often encounter large areas of fibrosis in which the circulation is necessarily poor, it would be best to add ,a course of BE inoculations according to the principle laid down in Table III, page 60. PULMOXAKY TUBEKCULOSIS 119 The essential elements in the conclusion of treatment Treatment for the mixed lire the treatment of mixed infection, and the removal of the infection be most ' elements which first encouraged the spread of the tubercular important * process, as may be gathered from a complete physical ex- conclusion of animation and a more detailed history. I am referring to * r atment - the possible presence of nasal obstruction, throat complica- tions, chronic bronchitis, and anemia, especially when due to constipation. The habits of the patient must be regulated with a view ' su P ervision of the patient's to the normal existence which he is to resume from now on. mode of life ft-, -, . i i i an d habits We must take great pains to remind the patient that must continue although he is no longer ill, he must not resume injurious d ^" n ^*^ habits which may have facilitated his infection in the that he ,. i rm . , . ., . , . remains under nrst place. Ihese instructions are more easily carried out observation. by our rule of keeping the patient within our professional sphere for two years following the conclusion of his treat- ment. In these cases especially, the testing of the patient every three months should not be overlooked. The -greatest care must be exercised in the conclusion of treatment of the ulcerative form of chronic pulmonary tuber- culosis. Here we have a condition similar to tuberculosis The conclusion of the bone. Just as in bone tuberculosis a cavity may i n th e e a u era- persist after the tubercular infection is ended, so also in t i of chronic the ulcerated form of pulmonary tuberculosis with cavity phthisis should formation, we must not expect obliteration of the cavity with j^^"^^ the eradication of the tubercular infection by means of the utmost care. tuberculin. Although there is a similarity in the process of formation of a bone cavity and of a lung cavity, we have an added disadvantage in the treatment of the latter, in as much as in a lung cavity we cannot by taeans of bismuth paste pre- vent the accumulation of suppurative material. In addition to that, we are constantly forcing infectious organisms into such a cavity by the process of inhalation. Fortunately, two factors exist which rescue this situation from becoming hopeless: the reflex cough, and perfect drainage by means of the bronchial tube. We must utilize these two factors 120 TUBERCULIN AND "VACCINE Opiates should be used very guardedly in cases of cavitation, as our only means of emptying the cavities is through the reflex cough. Treatment of the mixed infection should not be overlooked. to the best advantage so long as the cavity exists. And even though exhaustion and lack of sleep may make it neces- sary to employ remedies to lessen the amount of the cough, we must use them guardedly. By the too generous use of these drugs, infected and irritating material may become pent up which not only does harm by remaining in the cavitv, but which, through further accumulation might be forced -into the bronchioles and vesicles of the surrounding ' lung tissue, spread the infection, and even tend to produce a pneumonic process. It is self-evident, therefore, that we must keep our patient constantly fortified against mixed infection. A detailed description of mixed infection treat- ment and prevention, and methods that we must utilize to encourage the contraction of the lung cavity will be found in Part III of this work. I call attention to it here, in order to emphasize its importance. Tuberculin is hopeless here without attention to these details. Since the time necessary for the healing of a lung cavity is considerably longer than the healing of the fibrous form of lung infection, and as it is advisable to keep the patients under the influence of tuber- culin while they are still under treatment, it is best to utilize the longer of the two methods of BE administration (Table IV. page 60.) ACUTE OK ACTIVE. Acute pulmonary tuberculosis in- cludes in its category the most difficult cases to be treated by any method, especially ;with tuberculin. At the same time, this class of cases count the greatest mortality among them, so that a special method of therapy becomes much more urgent here than in any other form of the disease. If the careless use of tuberculin will produce the most harm in acute or active tuberculosis, we have at least this consolation and warrant for persisting in its use: the fact that we cannot do much to increase the serious- ness of the condition as it presents itself to us. Again, we can make our plea for tuberculin treatment in these con- ditions more persistently now that we have a method of PULMONARY TUBERCULOSIS 121 tuberculin administration which has raised the degree of safety to such an extent that it may be safely used in acute conditions. Any general practitioner who has used this method of tuberculin administration in but one or two eases where its us [was not very difficult, is qualified to use it in active pulmonary tuberculosis. We have only to classify our cases in order to be able to apply the proper auxiliary treatment. We must be able to recognize the difference between fever due to auto-inoculation and fever due to mixed A careful . ... -, i . distinction infection; between hemorrhage due to an ulcerative process as tothe and hemorrhage due to trauma that is brought about by ex- "^perature cessive coughing; between an afebrile case with an ulcera- and hemorrhage, and a more tive process belonging to the active form of the disease and guarded which is afebrile on ,account of having excellent drainage ^oTher* ' by being in close proximitv to a larger bronchus and an ^ m P tomswl11 J " discover their afebrile case which belongs to the chronic and slowly pro- cause to be ,,,,.. . in! other than the gressive type. . By making careful distinctions, we shall have tuberculin achieved two important aims which will help materially in the success of tuberculin therapy. In the first place we shall have removed many an obstacle to the successful prosecution of a course of tuberculin treatment, by treating symptoms which on, closer analysis will be found to b due to other causes than negative effects of the tuberculin. And in the second place, we shall have removed the necessity of expert classification of patients in order to judge whether tuberculin therapy is indicated or contra- indicated. This will be a great gain, for, instead of giving so much consideration to supposed contraindications to tuberculin therapy, we shall give closer attention to the treatment of the elements which bring about those contra- indications. In this way, we shall do much to remove the mysticism that surrounds tuberculin therapy and in its place discover many details in the condition of our patients. These details have been overlooked as a result of the hope- lessness which we have heretofore associated with the acute 1-22 TUBERCULIN AND The treatment of acute or active phthisis is begun with o.oooooi c.c. of OT, except in cases where the first few inoculations cause distinct local reactions, when the dose should be o.ooooooi c.c. The more rapid tuberculin administration is indicated where it is urgent to reach the maximum tolerance. condition, but if accounted for will go far to improve the condition of the patient. Beginning Treatment. It is quite safe to begin treat- ment with the fifth dilution in nearly all cases of acute or active pulmonary tuberculosis. There are, however, some exceptions, and these can be placed into two main classes. First, there are those acute cases where the tubercular process is recent, having begun as an acute infection. If after the first few inoculations with the fifth dilution, local reactions are prominent, it may point to the presence of a constitutional reaction which is masked by a high tempera- ture already present as a result of the active process. It is therefore better to go back to the sixth dilution in case of distinct local reactions following the beginning with the fifth dilution. Second, there are those cases of acute or active pul- monary tuberculosis which jare acute exacerbations of a chronic process that has existed for some time. These acute exacerbations are brought about yery frequently by mixed infection. All tubercular affections in the lung indicate beginning treatment with the fifth dilution. However, that may be far from the maximum tolerance, and since it is necessary to reach that maximum tolerance in these cases as soon as pos- sible, it is best to proceed with the dosage by increasing the increase at every inoculation instead of at every other inocu- lation. For example, the sequence of dosage would be as follows: Solution Number V, 0.10, 0.12, 0.16, 0.22, 0.30, 0.40, 0.52 c.c. and so on. This more rapid increase may be kept up until a near reaction is obtained, viz. : a distinct local reaction; distinct focal manifestations; the persistent occurrence of headache after two or three successive inocu- lations; or any other symptoms that may point to the approach of a constitutional reaction. Conclusion of Treatment. The conclusion of treatment must also take cognizance of the time of the origin of the PULMONARY TUBERCULOSIS 123 acute process, that is whether it is a beginning process with low resistance, or whether it is an acute exacerbation The conclusion of an old process. In the former case, the conclusion of i smuc h treatment presupposes the checking of the rapiditv of the s [ m P lerthan the beginning process, and being an early process it would require the of treatment, simplest conclusion. This means that after OT inoculations p roces *i a " are finished, the BE is administered as shown in Table III. checked > repair is For two years after the conclusion of the inoculations of rapid in Bacillary Emulsion tri-monthly tests, as described elsew r here, conditions, are required. Prognosis and Results. The prognosis in pulmonary tuberculosis, when viewed from the standpoint of immunotherapy, must be considered at three distinct periods in relation to tuberculin treatment. The first period is when the patient applies for treat- ment. An examination is made, and a fair knowledge is obtained from a physical examination, a microscopic exami- nation of the sputum, a three-day temperature record, and The prognosis an X-ray picture of the lungs. These, together with the beginning of history of the course of the disease prior to the beginning ^"** nt of treatment with tuberculin, when considered .together, form guarded in a basis for a fairly accurate prognosis. The history must, no element of course, take accurate account of the patient's loss of verlooked which may weight previous to this examination whether it was rapid have a or slow whether the present-day treatment, as the hygienic- up e onT t 8 dietetic and climatic treatment was applied and what effect it produced upon him whether it was discontinued on ac- count of the failure of the treatment, or whether the patient was impatient and did not give it a fair trial. Again, what are the habits of the patient and his mental attitude towards his occupation ? Can the failure of the climatic treatment be attributed to an intense psychic effect, caused by being deprived of his ordinary habits and pursuits? All these ele- ments play a far greater role in determining the prognosis of pulmonary tuberculosis than we have hitherto realized ; in fact, these factors play just as important a part as the stage 124 TUBERCULIN AND VACCINE of the disease. To a patient with a fairly advanced tubercu- lar lesion in the lung, who has demonstrated an inability to keep away from his ordinary pursuits, w can offer a much better prognosis with the ambulatory tuberculin treatment than to an incipient case who is willing to submit to the tuberculin treatment through bravado, but is constantly worried that he has probably chosen a hazardous method of treatment and would have done better with a change of cli- mate, etc. We must, in all events, remember that permanent damage will result after destruction of lung tissue and the symptoms remaining after the tubercular process has been cleared up, will be in proportion to the amount of destruc- tion that has taken place before the process has been checked. Temperature has a great bearing upon the prognosis at the beginning of treatment. If a patient runs a high tem- perature, prognosis is very difficult until the temperature has been checked or at least its nature determined. Jf it is due to auto-inoculation, it usually points to a rapid pro- gress with a tremendous hypersusceptibility and conse- quently makes the prognosis far graver than when the temperature is due to mixed infection. In the latter case, vaccines have been successful rendering the prognosis more hopeful when the temperature is caused by the mixed infection. The second period is when jthe patient has had sufficient once the tuberculin treatment to demonstrate a response. By this tuberculin . . treatment has time, a great many doubts which existed when the patient a e p "tive ated first a PP lied > have been cleared up. The progress of a tern- response, the perature at the beginning of treatment will at this time make barring * its elf evident. We shall know whether the temperature is ^"0^* controllable or otherwise; and if it was due to mixed infec- ybe tion, whether or not it responded to vaccine treatment. A aTfavorabie. change in the quantity of the sputum, or in its consistency, or in both, will have a (decided bearing upon our estimation of the efficacy of the immune response we have been able to elicit. A more decided localization of the physical signs in FIG. 35. A young man, twenty-two years of age, a bank clerk by occupation. About six months before he came to me for the first consultation, his brother died of pulmonary tuberculosis. He himself was always well, but he had grown very rapidly in height, and became very thin. About three years ago, he had a severe attack of grippe, which was fol- lowed by a cough and the presence of tubercle bacilli in his sputum. He went to the mountains where he recuperated and returned after about four months' stay, apparently well. ,0ne year and a half ago, he began to cough again, had night sweats, and hectic flush. In spite of the recent death of his brother and the fact that his own sputum was once positive, he refused to take his condition seriously, until I con- vinced him that it was an active recurrence. Upon the advice of an- other physician he decided to refuse tuberculin treatment, and went to Saranac Lake, where he remained three months with little improve- ment. He finally lost patience with the " rest in bed, and with the ever present tubercular patients all around him," and returned to New York City, where he applied for tuberculin treatment at my office. At this time there were physical signs throughout the right lung, and at the apex of the left lung. Tubercle bacilli in the sputum num- bered about fifteen to twenty in a microscopic field. This X-ray photograph, taken at this time, shows considerable infil- tration of the upper two-thirds of the right pulmonary field. The infil- tration seems to be of a connective tissue type. The left pulmonary field is clear except for slight clouding (indicating a recent process). PULMOXAKY TUBERCULOSIS . 125 the chest forms an important prognostic element which oc- curs as a result of effective tuberculin treatment. It indi- cates the disappearance of inflammatory changes, radiating from the actual point of tubercular infection during the more active tubercular process. This can only point to a favorable response to the treatment and of course it must necessarily improve the outlook for the patient. An improved mental attitude as a result of improvement in the general condition following the first inoculations of tuberculin will point to a better prognosis than perhaps an improvement of greater degree without the mental effect. Although tuberculin may elicit a response from the first A favorable dose, it nevertheless more often occurs after the maximum "tub^rcuHn " of tolerance has been reached. It therefore may require ma y become - 1 evident early the positive phase following a constitutional reaction be- inthetreat- f i -1 n . -1 _ .-.-I -i . ment, however fore a real beneficial immune response will become evi- itmaynot dent through the tuberculin treatment. Once a distinct appear until "111- late in the response to the tuberculin treatment is noticed, the prog treatment. nosis becomes a great deal jbetter, for nothing but an unusual occurrence, such as an unduly severe tuberculin reaction, or intercurrent disease, can stay the favorable progress wifli tuberculin inoculation once the patient Jias demonstrated a response. The third period is the prognosis at the conclusion of the course of tuberculin treatment. At this point it is not strictly prognosis that we have to consider, but the patient's present condition [and its bearing on his future health. The prognosis What is the amount of permanent damage left behind how ** j^",,^,, of much of the function of the lungs will be permanently inter- treatment will'depend fered with as a result of such damage how much of the upon the pathological change was brought about by a mixed infec- p^ e n f t tion and how well this mixed infection was under control damage 1-1111 produced by at the time all these elements have a great bearing upon the infection. the final results we may obtain with tuberculin. If frequent repetition may be pardoned, I will again state that in our expectations regarding the most optimistic results from 1 2 G . TUBEBCUUN AXD VACCINE tuberculin therapy we cannot overlook the fact that with the removal of tuberculosis as an ^infection, ,we do not eliminate the damage resulting from it. Hence the condi- tion of the patient at the conclusion of successful treatment will depend largely upon ,the amount and position of the pathological changes which have taken place during the life of the infection. The report of quantitative results obtained with tuber- culin in the treatment of pulmonary tuberculosis would have to embody such a large number of cases to make an impres- sion, that it is still beyond my experience to include a suffi- cient number in this work. For me to attempt a statistical statistics are exposition of the results obtained as given in the literature S a U "pJacticai m ou tne subject would 'be useless for two reasons : First, such guide." statistics may be gathered from almost any work on the subject, as most of the works on tuberculin treatment to be found at the present day consist mainly of statistics and consensus of opinions. Secondly, I have here presented a more simplified and more easily adaptable method of tuber- culin administration, which will produce even better results than have been obtained with tuberculin heretofore. As to the permanency of the results obtained from the treatment of pulmonary tuberculosis with tuberculin I have laid great stress upon the tuberculin test to be applied to the A greater patient for two years after the conclusion of treatment. This number of -11111 i c permanent necessarily adds to the results an element of permanency cures and not obtained in former reports. Since it is true' that the con- more lasting results are elusion of treatment is more or less empirical, just as in brought about ,1 f , i i c , i i by a more tne case * tne beginning of treatment, there are those cases where the conclusion of treatment may not have gone far conclusion of tuberculin enough, and a recurrence of hypersusceptibility may take pius'the* 11 ' place. And as it is well knewn that a recurrence of the hypersnsceptibility is a forerunner of the recurrence of the disease, it was found necessary, in order to assure the per- manency of the results obtained, to test the patient with tuberculin at certain intervals for a period of time after the tests. PULMCXXABY TuBEBCULOSIS. 127 conclusion of the treatment. These tests are made in order to determine in which of the cases the conclusion of treat- ment was not carried far enough. Thus we get ahead of the recurrence of the disease by overcoming the recurrence of hypersusceptibility. That is the reason why the results I have obtained although quantitatively not sufficient for an autho'ritative expose, can still claim qualitatively a superi- ority over former results. One more element should be reckoned with in the per- careful manency and frequency of better results obtained, that is *"^!ed the treatment of mixed infection which is given prominence inaction adds . . greatly to the in this work (see Part III). I am quite certain that permanency with proper attention given to the subject of mixed infection with due consideration to its .vaccine treatment, an element will be added to the matter of tuberculin therapy, which will add both quality and permanency to the results obtained. More important than statistics are the results produced The feeling in the various symptoms during tuberculin treatment. These bright a'bout results encourage both the patient and physician. The by tuberculin, ., . ~ . exerts a good .earliest and most striking effect that is noticed is the sense influence on of well-being 011 the part of the patient. Granting .that the ^JJ.^ larger part is brought about 'by " suggestion and auto-sug- the patient, gestion " it still adds an element which is most important to the favorable progress in the treatment of any disease. Pain. Tuberculin has a distinct anti-phlogistic action Tuberculin upon pain brought about by a tubercular condition, and will ^/^'for thus be found a great aid in relieving a symptom which tubercular causes most of the distress. However, pain produced by pleuritic adhesions occasionally persists >,even in patients who have noticeably improved, or remained well for years. Digestion. Both appetite and digestion markedly im- Digestion prove. That may be brought about by the general well- anda PP etite improve. being which is most sedative in its action upon neurotic digestion, or upon the improvement of the general tone of the digestive apparatus. Weight. The tuberculin treatment must be considered 128 TUBERCULIN AND VACCINE The increase in weight brought about by tuberculin is always accompanied by increased strength. Tuberculin is distinctly antipyretic in tubercular fever. The pulse improves with the other symptoms. Cough is diminished, and becomes less irritating. as having a direct influence upon the weight of the patient. That may be noticed upon the ambulatory patients who can- not change their mode of living in any way. (These patients, although they liave not gained in weight previous to the tuberculin treatment, gain in weight soon after the institu- tion of tuberculin treatment. And since nothing but tuber- culin has been added to the treatment, the result (must be attributed to .tuberculin. Of course, here again we may attribute such gain to the influence .of tuberculin on the general (Well-being, and to the improvement of digestion. Fever. The effect of tuberculin on fever cannot be mis- taken. Tuberculin acts as a direct anti-pyretic, and nothing will reduce temperature due to the tubercular infection as quickly as tuberculin treatment. Adverse opinion as to the effect of tuberculin on fever may be attributed to two dis- tinct reasons; first, the failure to differentiate between pyrexia due to tubercular auto-inoculation, and that due to mixed infection or other conditions; secondly, a faulty technic in tuberculin administration. Pulse. The influence of tuberculin on the pulse is in. direct proportion to its influence on the temperature and general well-being of the individual. If the tachycardia is due to a mild carditis which resulted from a long standing infection, tuberculin will have no effect upon it. It will have to be treated as a heart condition so .as not to allow it to dissipate the beneficial effects obtained from tuberculin. Cough. Cough may be increased as a result of the focal reaction accompanying the tuberculin treatment, but it is rendered less irritating and less strenuous. Later, as the effect of the tuberculin treatment becomes cumulative, the cough diminishes. This is especially true of the dry and irritating cough. Careful attention must be given to cough originating from other sources than the tubercular process, such as naso-pharyngeal conditions, mixed pulmonary in- fections, etc. Many a patient has lost patience with tJie tuberculin treatment because of the persistence of an annoy- FIG. 30 shows an X-ray photograph of the chest of the same young man* ten months later, at the conclusion of a successful tuberculin treat- ment. The infiltration has greatly diminished, the clouding has dis- appeared, while the apices alone show signs of a former tubercular lesion (permanent damage). For the past five months there have been no tubercle bacilli in the sputum, there is rarely any cough and the patient has been able to work ninety per cent, of the time during his tuberculin treatment. * As Fig. 35. PULMOXAKY TuBEKCULOSIS 129 ing cough after months of tuberculin treatment. The physi- cian should demonstrate this cough as originating from a condition quite apart from the tubercular process, and treat it as such without interrupting the tuberculin treatment which was producing the desired effect on the tubercular process. Hemoptysis. The general belief that tuberculin will Tuberculin produce pulmonary hemorrhage or even increase hemorrhage Beneficial when already present, is based upon a fallacy born of preju- effect on hemoptysis. dice. Tuberculin does not tend to produce hemoptysis. On the contrary, it will slowly diminish and finally permanently stop recurrent hemoptysis. Expectoration. The amount of expectoration may in- The tubercle crease at the beginning of tuberculin itreatment, but the baciiiiwm . ' more frequently consistency of the sputum will reveal a beneficial effect, disappear from The sputum becomes thinner and is jmore easily brought up. *^ e ri s n put The microscopical change in the sputum has not escaped the tuberculin notice of any physician using the tuberculin treatment. The than during diminution in the number of tubercle bacilli is striking, fol- an y ther treatment. lowed by a more rapid and more frequent disappearance of the tubercle bacilli, than with any other form of treatment. Even in hopeless conditions, a disappearance of the tubercle bacilli from the sputum may be accomplished with the tuber- culin treatment. This fact alone offers sufficient argument for the use of tuberculin in patients that are hopeless as far as a cure is concerned. Physical Signs. The physical signs are modified by tu- Oniysuch -,. . , ,. physical signs bercuhn treatment in proportion to the amount 01 perma- persist as are nent damage produced before the immune response became produced by the distortion sufficient to check the infection. Since scar tissue, distorted oftheiung lung structure, calcareous infiltration, constriction of bron- tnVhtaHng* 8 chial tubes, etc., will produce physical signs, it stands to of the disease - reason that such signs will persist, for any or all of these pathological changes form part of the healing process. Of course in early incipient cases all physical signs may dis- appear. When Tripier said that once a tubercular lesion 130 TUBERCULIN AND VACCINE in the lung presents physical signs, the lesion is incurable he really referred to the permanent damage, lung tissue never reforms, scar tissue must, take the place of the de- stroyed lung and thus change the normal physical signs. Fibrosis the Pathology. The consensus of opinion throughout the hMiilTgTn * literature as to the difference in the pathological changes in tuberculosis tuberculin treated patients and those treated without tuber- is usual in tuberculin culin, seems to leave no doubt that fibrosis occurs far more parents. frequently in the former than in the latter. This fact offers another important reason for the use of tuberculin, for "scar tissue formation is in the nature of all healing processes. It therefore offers a more lasting effect than any other form of healing. X-ray Findings. A wider adoption of jRoentgenography in pulmonary tuberculosis in recent years has become a great Roentgen- aid in the determination of results of tuberculin treatment anTmportant ( or ^ an J other treatment in pulmonary tuberculosis). field in Whereas the pathological findings had to be determined at pulmonary tuberculosis, autopsy and therefore had a more or less theoretical bearing upon the results of tuberculin treatment ;as compared with generally used, other treatments, the findings as shown by X-ray examina- tions are applicable to all stages of the disease. In these stages are included the more important class of cases that come under the arrested or healed conditions. Important contributions to the X-ray studies of lung structure, such as come from Kennon Dunham and others, Roentgen- by which we may determine the method of healing and the nndings C are progress of healing of the tubercular processes in the lung, of great aid will become the greatest aid to the wider adoption of tuber- culin in the treatment of pulmonary tuberculosis. Although this matter is yet too new to allow definite conclusions, it merits the attention which I wish to draw to it at this time. My personal experience has made me most enthusiastic. I would no more think of neglecting an X-ray examination of the chest, both at the beginning and at the conclusion of tuberculin treatment, than I would treat a patient with in prognosis. FIG. 37. Radiograph ic picture of the lungs of the same patient, whose temperature chart is here reproduced (Fig. 31, page 143). The lesions in the lungs follower! several extensive operations for tubercular glands of the neck. The last operation extended into the supraclavicular space almost exposing the pleura over the apex of the lung. As may be seen in the above X-ray photograph, the lung on the same side (right) is infiltrated and clouded throughout the upper two- thirds of its extent. The left lung seems clear. PULMONAEY TuBEBCULOSIS 131 tuberculin without a temperature record. I have included Figures 35, 36, and 37 to emphasize my purpose in calling attention to this subject. Not only are such demonstrations as shown in these illustrations helpful and gratifying to the physician, but the psychological effect on the patient alone merits the trouble and expense that an X-ray photograph may entail. CHAPTER VII MISCELLANEOUS TUBERCULAK CONDITIONS There are very few instances of tubercular infections, aside from those we have described in the foregoing chapters, which are not complications or extensions of the more impor- tant processes we have already described. However, since few of these processes may exist alone or are so prominent when they come to our notice the original process having become arrested special attention must be called to their treatment. The following are the conditions which need special mention. Tuberculosis of the Pleura in acute The tubercular infection of the pleura exists mostly as isbMt'to" a complication of pulmonary tuberculosis, and need not be discontinue considered, as far as tuberculin treatment is concerned, apart the tuberculin . treatment from the pulmonary process. It is only necessary to men- tion at this point that when pleurisy in an acute form, with symptoms * r atient does not definitely clear up the doubt as to the source of the temperature, we may resort to the expedient of administering the same dose a second time. ; This will have a two-fold advantage. In the first place it will verify the fact that the temperature rise was a reaction by producing a temperature again. And in' the second place, if the second inoculation will produce no temperature rise, it will avoid a reduction in dose and a slowing of the increases. Colds, mixed infection and many other conditions coming after a tuberculin inoculation may SPECIAL CONDITIONS 143 144 TUBERCULIN AND VACCINE The occurrence of tuberculin intolerance may be overcome by a change in the variety of tuberculin used. The more concentrated doses of BE are apt to produce abscess formation at the site of inoculation. simulate a constitutional reaction, but must be carefully recognized in order not to affect the tuberculin treatment. (Fig. 39.) Tuberculin Intolerance Occasionally it may happen during the administration of OT that after a constitutional reaction, any dose of OT, however small, will produce a reaction. This phenomenon is distinct from reactions caused by increased hypersuscepti- bility; for whereas, after an increased hypersusceptibility a change in the variety of tuberculin will make no difference as to the production of a reaction, provided a corresponding amount is used, in the case of intolerance a change of tuber- culin will stop the reactions, even if a much larger dose is used. It is therefore necessary in case of a sudden appear- ance of tuberculin intolerance, to change the variety of the tuberculin used. For example, if after a few months of treatment with OT, a tubefculin intolerance arises, and if at that time the second dilution was being administered, OT is discarded at this point, and a third dilution of BE sub- stituted. The treatment is then continued with the BE in the same manner as it would have been administered if OT were still being used. On reaching the first dilution of BE, the treatment is concluded in the usual manner as per Dose Table III, depending upon the tubercular process under treatment. Abscess Formation It was observed early, that the tubercle bacillus cannot be absorbed from the subcutaneous tissue when administered in the form of a vaccine, and when so administered lead to abscess formation. Thus it became necessary to pulverize the bacillary bodies in the manufacture of BE. However, it even now frequently happens that after the administration of BE pure, suppuration takes place around the point of inoculation, with final breaking down of the tissues. The abscess thus formed is more in the nature of a cold abscess, SPECIAL CONDITIONS 145 as repeated cultures of the pussy looking fluid that escapes have failed to produce any growth. As such abscesses break down by virtue of a tryptic digestion, healing takes place immediately upon the emptying of the abscess cavity. I have found that diluting the dose two or three times with normal saline, and inoculating the amount in two or three different places at one time, will avoid abscess formation. For example, if 0.20 c.c. of pure BE is the amount to be inoculated, 0.40 c.c. of normal saline can be drawn into the syringe with the 0.20 c.c. of pure BE, the syringe thor- oughly shaken, and about 0.20 c.c. of the contents inoculated in three different places, as far apart on the arm as possible. Autoinoculation I wish to draw special attention to autoinoculation, both The physical in order to distinguish it from tuberculin intolerance, and autoinoculation bv way of warning against its artificial induction. Auto- sho ?] dbe / t> avoided inoculation may be brought about by any means which forces as far as an undue amount of the tubercular material into the circu- lation from the localized tubercular process. An undue amount of breathing exercise may bring about an autoin- oculation from a pulmonary lesion. The use of a joint which is the seat of a lesion may force tubercle bacilli or the product of tubercle bacilli into the circulation. Massage over a tubercular area may bring about the same result. This is especially true of knee joint disease. The following is an interesting example of autoinocula- tion : A man, forty years old, had a very severe active lesion in the knee joint. After nearly a year in the hospital under the usual orthopedic treatment, a resection of the knee joint was advised. This alarmed the patient, who insisted on going home. After he had been at home for several months, ^* ampl ' : . ' The production I was called to see Mm. I found him wasted and pallid, of severe ,i .'i ,. >i,i -n L i autoinoculation with the entire right leg swollen to twice its natural size. through The knee was inflamed and the entire adductor region was massage i i ver tne a mass of hard induration. The pain, especially with the infected area. 10 14(5 TUBERCULIN AND VACCINE slightest movement, was agonizing. The least motion with his toe, the shaking of the bed put the patient into a quiver of pain. The severest ordeal that the patient had to go through was on being removed to the hospital. Four months of tuberculin treatment at the hospital was sufficient to bring about a quiescent state in the lesion, the surrounding induration, pain and tenderness disappearing, so that we were able to send him home on crutches. The tuberculin treatment was continued at his home by one of my associates. After four weeks of treatment at home, and after several closes of the first dilution had been administered, a reaction occurred, which was unduly violent, temperature reaching 105 F. On account of the violence of the reaction, a much greater reduction in dose was made than is customary after a reaction, and again a temperature of 104 F. occurred fol- lowing the inoculation. A still greater reduction in the dose was made after the second reaction, and a third equally vio- lent reaction occurred. A dose of 0.10 c.c. of the fifth dilu- tion was administered after the third reaction, but still a temperature rise to 105 F. occurred following this dose. It puzzled the attending physician, a great deal ; he called me into consultation. An examination of the patient disclosed nothing that would account for the increase of the hypersus- ceptibility. The local condition, in spite of the various reac- tions, had not become worse. I closely questioned the patient, insisting on an account of h,is actions forgery moment of the day, from Jbis getting up in the morning to his going to sleep at night. After a great deal of cross questioning, the fact was brought out that on the same day that the doctor called to give him his tuberculin treatment, ja friend of his, who is a masseur by profession, called on him, and administered a body massage, with particular emphasis on the diseased knee. This was done in a friendly spirit, and " in order to improve his circulation." That it might produce harm was so remote from the patient's mind that he neither mentioned these massages to the physician treating him, nor to me. The mas- SPECIAL CONDITIONS 147 sages were discontinued, and upon lay advice 0.10 c.c. of the second dilution a thousand times the dose which sup- posedly produced the last reaction was administered with- out the least sign of a reaction. In the next" four or five treatments the same amount was reached that was adminis- tered when reactions .began. From there on the treatments were continued uninterruptedly. In about a month from that time he came to the Out-Patient Department of the Xew York Polyclinic Hospital, for conclusion of treatment, making his bi-weekly trips without any trouble. In less than a year from the beginning treatment, he returned to his occupation as baker. The only way to overcome autoinoculation is by reducing the activity of the part affected. In febrile pulmonary tuber- culosis, rest in bed will reduce temperature if it is caused by autoinoculation. Tri-monthly Tests To one who has had a large experience in the tuberculin Periodi treatment of tubercular conditions, the following important fact is evident: any recurrence of the process after it has tests after the been arrested during the tuberculin treatment is accompanied tuberculin by a recurrence of hypersusceptibility. It occurred to me some years ago to follow up the treatment of a series of patients after the conclusion of tuberculin treatment to de- termine at intervals by a tuberculin test 'any tendency for the recurrence of hypersusceptibility. I thus found that the recurrence of hypersusceptibility precedes the recurrence of a tubercular lesion. (A series of tuberculin inoculations was instituted in every case that showed a recurrence of hypersusceptibility. As a result no recurrence of a tuber- cular lesion took place in the last few years that these tests were carried out. The systematic tri-monthly tests were adopted as a con- sequence of these findings. By applying tuberculin test every three months, for two years following the conclusion of tuberculin treatment, we were able to get ahead of any 148 TUBERCULIN AND \' r ACCiNE Appropriate tuberculin treatment to overcome recurrence of hypersus- ceptibility will prevent a recurrence of the disease. Example: The recurrence of hypersus- ceptibility in a case clinically cured. possible recurrence in all cured cases. A dose consisting of 0.10 c.c. of the first dilution of OT (0.01 c.c, of OT pure) is administered as a test in all cases except where there was a definite history of an infectious disease having attacked the patient between the conclusion of the treatment and this test. If an infectious disease did intervene the divi- sional method of testing should be adopted ; that is, 0.10 c.c. of the second dilution is given as a first test; 0.50 c.c. of the second dilution forty-eight hours later; and then 0.10 c.c. of the first dilution as a final test, forty-eight hours after the second test. Should any of the tests prove by a constitutional reaction that hypersusceptibility has returned, the patient should again be put on the tuberculin treatment, beginning the course with a tenth of the quantity of tuberculin which caused the reaction, and concluding in the same manner as in the original course of treatment. The following cases will illustrate the importance of the tri-monthly test in the detection of recurring hypersuscepti- bility, and the value of treatment to prevent recurrence of the disease where the test is positive. CASE I. A young man twenty-four years of age, had a negative family history, with the exception of a sister who had tubercular adenitis. His past history showed that he had had measles and chicken pox some time before he was ten years old. Otherwise he was well and strong until five years before the beginning of treatment. At that time he began to have attacks of cramps in the abdomen, which began at the pit of the stomach, radiating and finally settling in the region of the appendix. Nausea and vomiting, followed by diarrhea, would frequently accompany these attacks, which recurred every three or four months, and would last from one to four days. 'On account of the absence of rigid- ity over the appendix, a definite diagnosis of appendicitis was not made, but he was treated for " stomach trouble and inflammation of the bowels." In September, 1915, an attack SPECIAL CONDITIONS 149 occurred which was more severe than usual, lasting a week. Another attack followed in October, which persisted for ten days. At this time an operation for appendicitis was advised and carried out in the early part of November. At the operation the tubercular nature of the trouble was discov- ered. The tubercular process existed not only in the mesen- teric glands, but also in the pelvic, peritoneal, and prostate glands. Five days after the operation, severe pain began in the rectum, and after the patient had been kept under the influence of morphine for several days on account of the severity of the pain, the pain suddenly disappeared on the appearance of a large amount of pus in the urine. After a stay of about three weeks at the hospital, he was referred to me for tuberculin treatment, which was begun on December 11, 1915, and ended on September 14, 1916. During the course of treatment he had only two constitu- tional reactions. His weight at the beginning of treatment was 148 pounds, which was far below normal weight for his height, and increased to 175 pounds at the conclusion of treatment. The pus in the urine, and the pain in his back and rectum disappeared. Only one attack of abdominal pain occurred soon after beginning the tuberculin treatment, and has never since recurred. Six months after the institution of tuberculin treatment, he returned to his occupation, and has kept at it since. He received the first tri-monthly test in December, 1916. The dose was 0.10 c.c. of the first dilution, and was followed with negative results. The second test was given in March, 1917, and to the surprise of both patient and myself, there was a severe constitutional reaction, the temperature rising to 101 F., pain in the abdomen and in the back being quite severe during the rise in temperature. This patient seemed to have so thoroughly gotten over his disease that I was not at all insistent about his coming .for the tests. But as he put it, " the dread of the return of the disease was so strong that he would not miss a single direction given him during 150 TUBERCULIN AND VACCINE treatment," and so he came punctually for the test. The reaction which followed the second test occurred as the result of 0.10 c.c. of the first dilution. His treatment was resumed with 0.10 c.c. of the second dilution. Example: CASE II. This child, a five-year-old girl, whose family cohered' 8 history is negative, was three years old before it was dis- recun-ence covered that she had tuberculosis of the left knee. X-ray of hypersus- ceptibiiity findings showed a mild lesion in the epiphysis of the femur, afteTTiT 8 with some erosion of the posterior surface of the patella. infectious After wearing a cast for two years, tuberculin treatment was disease, followed by instituted and continued without interruption until a dose o/thedisease ^ ^.80 c>c - ^ tne ^ rs ^ dilution of BE was reached in Au- gust, 1915. There was at this time a complete functional cure. The child seemed in perfect health and was discharged as cured by the physician who had administered the tuber- culin according to the technic outlined in this work. On ac- count of the seemingly good result obtained, the doctor did not urge upon the parents the continuation of the treatment, nor were they instructed to bring the child for the tri- monthly tests. Six months after the last dose of tuberculin the child took sick with measles. Two or three weeks later she began to complain of pain in the knee, with limitation of motion, and there was a temperature (rectal) rise to 101 F. daily. In this case, treatment was resumed with the third dilution. SPECIAL CONDITIONS 151 l 21 OS 3 "C i j] qio 152 TUBERCULIN AND VACCINE PAET III SPECIAL TREATMENT CHAPTER I INTRODUCTION Up to the present day. most of the work done with tuber- Tuberculin should not be culin has been done by lung specialists, and in sanatoriums employed to where the hygienic dietetic treatment, and all other adjuncts O f other US of tuberculin treatment have been followed out as a matter ^"pe^c measures. of course. However, in the teaching of tuberculin treat- ment the importance of these measures as an adjunct to tuberculin has been overlooked, resulting in their neglect when tuberculin was given a trial. Since this work is calculated to emphasize the value of T f h , c t ctic * ot tuberculin tuberculin in surgical tuberculosis, the use of tuberculin is specific would be doomed to failure, in the large majority of tubercular cases, were we to neglect the other measures which are "just mfectl n> and not as vital in bringing about a cure. We must bear in mind against the that tuberculin can overcome only the infection; that the processes disease, which in surgical cases has persisted for years, has which occur as a result left its traces behind in the form of pathological changes; of the and that unless we apply correct measures to these at the infection" same time, we cannot hope to produce appreciable results. To the patient, it is just the same whether his fistulas . ,. , The consequent or bone cavities are kept open with a discharge of pus due processes may to the streptococcus or staphylococcus, or whether the dis- f ont ' nuethe * invahdism charge is due to the tubercle bacillus. While from a medical after the standpoint, the elimination of hypersusceptibility with tuber- O f the culin is already of great advantage to the patient bv check- tubercular process. ing, as it does, the further spread of the tubercular process still, the local manifestations of mixed infections are just as troublesome and tend as much to invalidism as before. l.Vt TUBERCULIN AND VACCINE The application of orthopedics is necessary to bring about good results from tuber- culin therapy. Tuberculin therapy will act as a guide to the application of orthopedic treatment. Surgical interference must be limited to the conditions outside of the influence of tuberculin. Aeain, tuberculin must not be understood to take the c? / place of orthopedic treatment, for the deformity is not caused by tbe tubercular infection itself, but by the results of the tubercular process. In arresting the infection with tuber- culin we do not correct deformities and do not replace de- stroyed joints or bones. At the same time, although the aim of orthopedic treat- ment is to prevent or correct deformity, it cannot claim to ^top the infection. And all orthopedic appliances can be of no avail, unless during their application, a natural resist- ance overcomes the infection. Otherwise, in spite of the appliances, even under the best of circumstances, the recur-: rence of these deformities may take place. However, the combination of orthopedic and tuberculin therapy is ideal: the immunotherapy to limit the disease and to overcome susceptibility, the ortho-therapy to prevent deformity. The tuberculin will, moreover, act as a guide to the limitation of orthopedic treatment it will be unneces- ary to order the cumbersome appliances to be worn year after year, for tuberculin will do away with the element of " guess," which has to be so prominent in orthopedics. For with the conviction of having checked the infection and over- come the susceptibility, the length of time for orthopedic application can be gauged more accurately. The same holds true of the application of surgery in tuberculosis. Eliminating the danger of extension of the disease by overcoming the jsusceptibility to tuberculosis be- fore surgical interference, will not only reduce to a minimum the amount of surgery required, but that which is required can be done with greater safety. Cicatrized tubercular glands may be removed under local anesthesia, with the most conservative incision, whereas tubercular glands removed without a previous tuberculin treatment very frequently recur even after a radical opera- tion. Whether tuberculin treatment is necessary to make other INTRODUCTION 155 methods of treatment efficient, or whether other methods Tuberc " losi s is a combina- are needed to make the tuberculin a success, the fact remains tion of that a combination of certain methods of treatment is vastly hence a' superior to each one alone. combined therapy is We have also advocates of bismuth paste in tubercular most rational, cavities and abscesses. There is 110 doubt that in isolated cases we have good results from the use of bismuth paste alone. And since we cannot differentiate between the cases which should have bismuth alone, and which should have tuberculin alone, why not avoid failure from a wrong choice by using both, in all cases ? There is no doubt that the bismuth acts purely mechanically by establishing a high spe- cific gravity in the cavity or fistula. It thus prevents nega- tive pressure, which is the cause of exudation of serum and lymph, the accumulation of which forms the best culture medium for the further growth of bacteria and thus con- tinues the pathological process indefinitely. So by the use of bismuth paste, we overcome a prominent ,f actor that con- tinues the subjective symptoms of the disease which is be- yond the province of the mechanism of immunity. As regards the application of hyperemia, the tuberculin therapy is again of inestimable value. Bier reports excel- lent results with hyperemia alone, and since the part of the mechanism of the immune response is a focal reaction con- sisting of hyperemia, the introduction of Bier's hyperemia may be of great value during the course of tuberculin treat- ment. In fact, in isolated cases, it may provide the elements of success in an otherwise stubborn case. There might have been some obstruction to circulation, or some other element which may have prevented focal reaction ; or the antibodies may not have been able to reach the point of infection ; but with the addition of the artificially induced hyperemia, we were able to bring the immune elements to the* point of the local infection. Since we are dealing here with the natural forces that are instrumental in overcoming infection, and the assistance 156 TUBERCULIN AND VACCINE we give consists in intensifying these processes, the usual The necessary, surgical measures that are deemed necessary can be more or l^rgica 1 *" less modified, not only as to the time of operations as sug- measuresmay g es t e d above, but also to the extent of these surgical meas- modified in the ures. Thus, if the increased supply of antibodies will over- fn'reasing 1 come the bacterial invasion, it stands to reason that the immunity evacuation of the pus already present is quite sufficient with- acquired dur- ,-,., / T-< i ing tuberculin out the establishment of drainage, -bor the same reason, treatment w ^ e incisions may be dispensed with, and either aspiration or puncture may suffice. At any rate, the increased immune response will eliminate the danger of the spread of 'the in- fection even though it may not be quite enough to prevent the local formation of inflammatory products. In this case, the puncture will be sufficient to prevent such discharges from being retained ; and the trouble of re-aspiration will be more than repaid by the final cosmetic effect. The cold In this connection, it is also well to remember that the point ing of cold abscesses may not be due to mixed infection at all, but to a digested ferment which is excreted by the than has been cells lining the abscess. These ferments digest the tissues of >rded to it. tne wa ]j^ en i ar gi n g t ne abscess in all directions, giving it the appearance of pointing when the process approaches the sur- face. Puncture or aspiration is absolutely essential under these circumstances before the process has come too near the surface; for unlike an infection, there is no inflammatory hyperemia surrounding the area where the abscess breaks through. Hence, the unresisting surface forms more or less a sloughing process, causing a very ugly broken-down surface with ultimate extensive scarring. CHAPTER II The subject of mixed infection is recently receiving TOO little attention given to more attention than it has been getting for some time. How- ever, it still falls far short of the attention that it deserves. c - existin g infections One cannot work in tubercular conditions very long without in tubercular becoming convinced that many a patient would have suc- ceeded in overcoming the tubercular infection were it not for a mixed infection that kept the flame smoldering. One need not be surprised in coming here and there upon The removal a case where a vaccine for a mixed infection will clear the "nfe'ction^m whole trouble. The balance between the infection with the clearly define tubercle bacillus and the mixed infection with the other the tubercular bacteria is sometimes so fine that it is difficult to determine process> a " d thus simplify which is producing the symptoms. This is particularly true the tuberculin ,. . Trr -i ,. . treatment. in patients running a temperature, we can avoid wasting a great deal of time during the tuberculin treatment when a temperature is caused by mixed infection ; for if we consider that temperature of tubercular origin, the amount of tuber- culin we are advised to give (Will be far less than for a simi- lar condition without temperature. Xow, if we can clear the temperature by means of a mixed infection vaccine, the tuberculin treatment in such cases will then be more definite and accompanied by less hesitancy as to its con- tinuation. Perhaps a great deal of hesitation in the use of vaccines The empirical in mixed infections is due to the indefinite results often ob- of va'ccines tained with them. These faulty results are another illus- has hindered " . their wider use. tration of the ineffectiveness of the stereotyped use of a therapeutic agent that depends upon the stimulation, of natural processes which are so complicated and so different in different individuals. We cannot administer vaccines any more than tuberculins in formulated recipes, as we admin- 158 TUBERCULIN AND VACCINE ister drugs. Nor can we use vaccines .without absolute definite reference to the causative bacteria, to the virulence of the infection, and to tie individual resistance. Diagnosis of Infective Organism A correct ^ momentary contemplation of the heading of this topic diagnosis of the causative will impress the reader at once with the importance of this CM" ' S subject. Nevertheless, very little has been said on this sub- before a proper j ec t j n th e past, and still less has been done. It is therefore Obtained for clear that the element which would have rendered the whole subject of vaccine therapy much simpler and infinitely more infection. scientific has been entirely overlooked, namely, the bac- teriological diagnosis of the -infection. Some have depended upon the laboratories to make their vaccines and to give the directions for their use; while others have used mixed vac- cines which were supposed to be applicable for all forms of infection. Again, proprietary mixtures were employed with 2 list of diseases [for which they should be used, and with directions for dosage. As neither the laboratory nor the proprietary manufacturers can have any idea of the condi- tion in question, the physician administering the vaccines not only fails to understand the composition of the vaccines, but is just as hazy with regard to the infection with which he is dealing. All this forms a condition in the sphere of immotherapy that may lead not only to bad results but even to a premature death of the entire subject. Such a state of affairs would bring about no less a calamity than the loss of the value of tuberculin in tubercular conditions. How different would the aspect of vaccine therapy be if due consideration would be given to the diagnosis of the infection? Once the diagnosis of the infectious organism is established, we could then demand from the laboratory a vaccine made from the infectious organism no matter what other bacteria happened to contaminate our culture media or our infected material. INFECTIOX 159 Or if the stock vaccine be used, we could simply pur- chase a vaccine for this particular infectious organism. We could then treat the patient with the specific vaccine, and abandon the use x>f a mixture of organisms which we have been using with the hope that one of them may reach the mark the rest having no bearing on the infection. Having made the diagnosis, the appropriate vaccine will be an agent of precision in the hands of the physician, and will do away with probing in the dark which is brought about by an in- sufficient knowledge of what is being accomplished during treatment. . It will be possible to gauge the treatment by the condition at hand, and acquire that exactness which alone will make possible the clear insight into the mechanism of immuno- therapy. To arrive at an exact diagnosis of the infection, we have the following methods at our command: the smear for micro- scopic examinations ; cultures on appropriate culture media ; physical diagnosis; and animal inoculation. Smear Diagnosis. It is not necessary to have a special A simple smear biological training in order to be able to utilize this form of ^ethyie^'biue, diagnosis. The variety of bacteria that we deal with in the wil1 disclose . f . * -, .,,. .,.,.. under the more common infections and especially in mixed infections microscope in tubercular patients are few in number and easily dis- thecausatlve " organism in tinguishable. A few hours of reading in any of the simpler the large text-books on the subject will be sufficient to give all the instances, data that are necessary for a working basis in vaccine therapy. In the majority of cases, the simple methylene blue stain will suffice. In others, a differential stain for the tubercle bacillus and perhaps Gram's stain may be used. All in all, the making of a smear diagnosis of mixed infection consists in making on a slide a smear of the pus discharged from a fistula, or sputum ; fixing it in the flame ; then covering it with an aqueous solution of methylene blue for a minute or two ; rinsing the slide ; then when dry placing a drop of 160 TUBERCULIN AND VACCINE cedar oil on it; and finally examining it with the oil im- mersion lens. The staphylococcus, jthe streptococcus, the colon bacillus and the pneumococcus are so easily distinguishable that one does not require a second glance in the microscope to recog- nize the offender. Of course, frequently secretions contain so few of the offending organisms that we must depend upon a cultural growth for diagnosis. (This subject will be dis- cussed under the heading of " Cultures.") But a short practice with smear diagnosis is required to make it evident that very frequently the offending organism fails to grow in the culture tube even though it is evident in the smear. It is a known fact that the more virulent a bacteria, the greater the difficulty in obtaining a growth on an artificial medium ; and that the avirulent strains not only grow more readily on the artificial medium but will inhibit the growth of the virulent bacteria which are necessary for the production of the vaccine. Thus it may happen, that the smear shows a streptococcus, while the growth in the culture tube reveals a staphylococcus, the latter having either gotten in through a surface infection, or from the pus where it took no part, in the actual infection. This staphylococcus being avirulent, crowded out the streptococcus by its rapid growth. So long, however, as a smear revealed the strepto- coccus as the causative organism, a second or even a third culture will finally yield the proper growth for a vaccine. If a culture is sent to a laboratory, the request must accom- pany the culture to make the vaccine of the organism found to be the one causing the infection. The laboratory will find no difficulty in isolating the causative organism through sub- cultures, and if it fails to grow, the laboratory will so report to the physician and avoid making a vaccine of the wrong bacteria. This can be accomplished only by a correct diag- nosis of the causative organism in the first place. A large number of failures in vaccine therapy will thus be elimi- nated. Moreover, the practice of smear diagnosis brings us "'* ..../* t./ ^>'..* MIXED INFECTION 161 face to face with ,the enemy we are fighting, consequently simplifying the whole subject; and since simplicity leads to precision, the labor involved carries with it a commen- surate compensation. Cultures. One of the important points of consideration The appearan in the steps between the infection as it presents itself to us and the vaccine is the inoculated culture tube. The proper aidinth diagnosis of media are easily obtained and all that is necessary in order the causative to get. the proper vaccine is ,a growth of the bacteria that is causing the infection. The culture tubes are put up in con- venient form for inoculation and transportation. However, if we are to utilize ( the appearance of cultural growth for diagnosis, we have to grow the bacteria in our office, and at the proper incubation temperature. Here again, a serious barrier to yaccine therapy seems to arise in the shape of costly and Complicated apparatus. If we remember, however, that the essential for the growth of the bacteria is a temperature of 97 to 99 F., the means by which we can maintain such temperatures is of no conse- quence. Hence, it sometimes suffices to carry the culture tube in the inside vest pocket, if a culture is taken in the morning, in order to obtain a sufficient growth for diagnosis by the evening. Another convenient means of incubation is a thermos bottle. This may [be (filled with water at a tem- perature of 101 or 102 F. The infected culture tube when placed in water, will reduce the heat to about 98 F. Care must jbe taken to prevent the water from entering upon the culture media. The cultural growth of these bacteria is required not only for the diagnosis of the invading organism,' such as the differentiation between the albus, aureus and the citreus forms of the staphylococcus ; but it is also necessary where the laboratory for the making of the autogenous vaccine is at a distance, requiring the transportation of the culture tube under adverse temperature conditions. Under these circumstances, the growing of these bacteria before trans- 11 TUBERCULIN AND VACCINE The diagnosis of the causative organism by means of animal inoculation is so seldom necessary that it requires no consideration here. The physical appearance of the pus and of the infected area may sometimes aid in the diagnosis of the causative organism. portation or exposure will make it possible for these bacteria to reach the laboratory alive. Wte know the difficulty in growing the streptococcus; how quickly it dies under the best conditions in the culture media. An incubation at proper temperature for about twelve hours will so increase the number of these bacteria that a sufficient number of them will reach the laboratory for sub-culture and for the manufacture of the vaccine. Here again, as in the case of the smear diagnosis, an intimate knowledge of the physical ap- pearance and of the characteristics of these few important organisms is essential a knowledge that will not only bring about a gratifying understanding of the subject, but will help materially in the success of immunotherapy. Animal Inoculation. Fortunately bacterial diagnosis does not frequently call for animal inoculation. When it does, it applies only to the tubercle bacillus. 'Many cases where animal inoculations may be thought necessary can be cleared up by resorting to tuberculin tests as described under their respective headings in the chapter on " Tests." . Thus the field of animal inoculation is exceedingly lim- ited. In those exceptional cases where this method remains the only source of diagnosis we must resort to it only if we are not within reach of a well-equipped laboratory. Otherwise, it may be found simpler in such instances to give a course of tuberculin even if it entails the eventuality of treating a non-tubercular case with tuberculin. ~No harm can be done with tuberculin in a non-tubercular case, whereas a great deal of good will be accomplished if the case is tuber- cular in nature. Physical Signs. Occasionally we have to deal with an urgent form of mixed infection where it is necessary to use a stock vaccine immediately and where the infection is beyond reach, making a smear or culture impossible. In such cases we may sometimes get a fairly good clue to the nature of the invading organism by means of physical signs. Thus, the temperature curve may point to a streptococcus infection. MIXED IXFECTIOX 163 An erysipelas can be diagnosed from outward appearance and a stock erysipelas vaccine used. A septic condition with a sero discharge may point to a streptococcus infection ; and a creamy discharge, to a staphylococcus. The odor of a dis- charge may point to the colon bacillus. The location may occasionally be a clue, as for instance, a mixed infection in kidney tuberculosis would point to a colon infection. The following history illustrates the importance of the correct diagnosis of the causative organism. The patient, a woman twenty-eight years of age, was operated on by suprapubic cystotomy for severe hemorrhage into the bladder from tuberculous ulcerations in the bladder wall. Three or four days later she had a severe chill, followed by temperature rise to 104 or 105, and for ninety-three days this daily temperature rise continued, with remissions to below normal. Her condition at this time became very grave. She was greatly emaciated. About the ninetieth day, tubercle bacilli were found in her urine and for the first time the tuberculous origin of the trouble was discovered. This discovery was responsible for my being called in on the case by the attending physician, who knew my work with tuberculin. The question of vaccine had not been considered up to this time. As previously stated, acute infection had now lasted for ninety-three days, and on examination I found her suf- fering from what appeared to me to be a streptococcus septicemia. All urine came from the suprapubic incision, but was not recognizable as urine; it was a thick, creamy discharge having a microscopic appear- ance of pure pus and which on analysis showed urinary elements. A microscopical examination showed numerous tubercle bacilli, a short- chain small streptococcus, a staphylococcus, and a small micrococcus, the identification of which we did not deem worth while at the time. Suitable culture media were at once inoculated and a vaccine of the streptococcus was ordered. Meantime a stock streptococcus from a similar condition was at once administered in order not to lose time in waiting for the autogenous vaccine. Eepeated laboratory reports, after cultures on various media, stated that no streptococcus grew in the media, and not until almost a week had elapsed did .the streptococcus finally grow. Until then the growth always showed a small micrococcus unidentified, a staphylococcus, or the colon bacillus; but these were rejected as I was convinced from the pus appearance in the smear, and from the course of the infection that the streptococcus was the causative organism. The stock vaccine proved efficient ; not only had the patient 'a temperature dropped to normal within forty-eight hours after the first inoculation, but after three more inoculations, during a period of two weeks, she was out of bed. Pure urine appeared from the suprapubic wound with only a microscopic trace of pus. Tuberculin treatment was instituted ten days after the first inoculation of vaccine. During the following four months of treatment, the suprapubic wound closed com- pletely; the urine became free from tubercle bacilli; and the patient's weight which had been ninety pounds increased to one hundred and sixteen pounds. Incidentally this case demonstrates the successful treatment of renal tuberculosis with tuberculin. It is now a year since the conclusion of treatment, and none of the symptoms referable to renal tuberculosis or bladder ulcerations have reappeared. CHAPTER III. VACCINES Definition. it does not come within the scope of this work to give a detailed account of the methods of preparing vaccines. I shall enter into it more in detail in a forthcoming work dealing with vaccines exclusively. However, I might men- tion that a vaccine is a watery suspension of dead bacteria, the bacteria killed in such a way as to produce the least morphological or chemical change in the bacteria. Such alteration must be avoided in order that the bacteria retain Their power of stimulating the specific antibody when inoculated. Preparation It is necessary to make sub-cultures from the original inoculated media, in order to make sure that we have a pure culture of the specific bacteria. A sufficient growth on the sub-culture must be obtained in order to get a sufficient i n the quantity of vaccine for the entire treatment. 'For after vaccine treatment has been instituted, it may become im- of vaccines ' a sufficient possible to obtain growths from the discharges even though complete the complete immunity has' not yet been established. This would treatment necessitate waiting for a recurrence of the infection in order should be made. to be able to obtain more vaccine, thus causing unneces- sary delay and vitiating to a large extent the former vaccine treatment. Standardization. The standardization of vaccines must be made as nearly accurate as possible. I have seen a great deal of harm done by faulty methods of standardization. Proper The following example may serve to bring out the necessity standardization *. " * is essential. for proper standardization more effectively than any dis- course I can give on the subject. A comminuted fracture of the elbow joint became in- fected, and showed the staphylococcus albus in pure culture VACCIXES 165 as the causative organism. A vaccine was made, and stand- ardized by a method of comparison of the viscosity of the vaccine with test tubes filled with known strengths of vac- cines. The first dose administered produced a violent nega- tive phase. The violent rise of temperature and tremendous increase of the local inflammation was not attributed to the vaccine, but to the extension of the infection. I was sum- moned in consultation ; and from the appearance of the tem- perature curve, I was convinced that it was due to a nega- tive phase. The undue turbidity of the vaccine led me to bring it to our laboratory for re-standardization. The bac- terial count disclosed the vaccine to be nearly one and one- half times as strong as the label read. The infection cleared up after two injections of the vaccine, doses being used according to the new standardization. The effect was so marked that it left no room for doubt that it was brought about by the proper use of the vaccine. The best methods of standardization of bacterial sus- pensions in use at the present time are: 1. Wright's Method, which requires the mixing of equal parts of freshly drawn blood from a healthy indi- vidual (usually from the worker's own finger), and bac- terial suspension diluted and stained, and placed in a count- ing chamber, in the same manner as for red blood count. The number of bacteria and the number of red blood cor- puscles are counted in a number of squares, and an average is obtained for each. By figuring the proportion between the bacteria and the red blood corpuscles to the known five million red blood corpuscles per cubic millimeter, the num- ber of bacteria per cubic millimeter will be obtained. This number multiplied by ten will equal the number of bacteria per cubic centimeter. 2. By a direct count of the number of bacteria, in the same manner and by means of the same apparatus as a blood count for the number of red corpuscles is made. For more specific directions, see any laboratory guide. 160 TUBERCULIN AND VACCINE Improper containers will frequently produce negative results from vaccine treatment of mixed infection. Example. Containers. At first glance, it may seem trivial to even mention the subject of containers for vaccines. But the success of vaccine therapy may sometimes depend on a minute detail. For one thing, the former method of dispensing vaccines in ampules should be discarded. The sealing of the ampules necessitates the drawing out of the heated glass to a very thin neck. If, perchance, the box containing the ampules is allowed' to stand for a day or two in such a position that the ampules are upside down within the box, the bacteria will precipitate into the very thin neck. "When the vaccines are administered, these thin necks are filed or broken off and thrown away with the active principles of the vaccines. Even though we recognize the precipitated bacteria in the neck, and attempt to shake it out into the body of the ampule, we may in many instances only half succeed and so make our administered dose quite different from our in- tended one. The following case will not only illustrate the necessity for good containers, but will emphasize the fact that atten- tion to details is absolutely necessary when dealing with immunotherapy : A girl, twelve years old, was sent to me for advice as to the use of vaccine for a colon pyelitis. One year previously she had a kidney removed for the relief of a severe pyelo- nephritis. Since this was an infection of her only kidney, surgical intervention was out of the question this time, this fact forming the main reason for referring the case to me. I advised the use of vaccine, and gave full directions as to dosage, etc. Three months later the little patient was brought to me by the mother, upon the advice of the physician in charge, with the statement that the vaccines had produced no result what- ever. The temperature records showed that the daily rise between 101 and 102 F. previous to the vaccine treatment, had in no way changed during the treatment. Urine exami- Uf i c O> ^ O a Cu V = V. - *T o> j. r ^* o _2 w 8 |H . 50- 0) fl g ~ ** -S-^s C ' l 9 w i 1 V ^E 03 c 5 O w ^ f_, w 03 G eo 0) a H ja "3 ~ F-i W SJ -* M H ** >. C ~ H *J iS 5- fl c w z O fl 0) III 11 U.) $ & C O V ^ M 2 *o C r-i M c o & I Tx - aT 5 S at 1 1 ~ 'r _, be S C pj ^ o ft ^, s -= eS fl" V ~ H "a II 1 X -^ 00 F4 ^ o 0) m C -u 0> 4-1 o - | PE 0} R e3 jj ^ w c s / !2 o - . -4- *-t i j O GJ H Ti bo a ~ r. S o> fl 0> >% ^l tH *s DO 5 ~ d = 5 C O 7. 0> M " T;. "3 1 DO H * ^ ,2 s ''S / '3 m W ^9 _t p t5 o "^ .3 g M a V 1 ' O O) .5 VACCINES 167 nation showed just as much pus and bacteria as ever. Since vaccine therapy in this case was considered a method of last resort, the child was now again referred to me with the hope that personally I might be more successful than through the physician in charge. The patient's mother brought with her the autogenous vaccine which consisted of a box of ampules, each ampule containing one cubic centimeter of the vaccine. This vac- cine was made at the Polyclinic laboratory and there was no question as to its proper standardization. I took one ampule and noticed the precipitate in the neck. I began to shake it very vigorously, and continued to shake it for some time until all visible precipitate was out, and the clear fluid in the body of the ampule became viscid. I then broke the. neck off and drew the appropriate amount into the syringe ready for inoculation. My vigorous efforts at shak- ing the ampule attracted the attention of the little girl, who thereupon exclaimed to the mother, " Doctor never did that. Has something happened to the vaccine on the way over ? " The reason for the failure of at least eighteen inoculations of vaccine given previous to this consultation at once became evident. The child had been inoculated with normal saline plus one-half per cent, phenol, but with no vaccine. That went into the waste with the discarded neck of the ampule. After two inoculations at my office the temperature was normal and after four more all traces of pus disappeared from the urine. The child gained rapidly in weight, increas- ing in the next thirteen months at least forty per cent, over her former weight. The best container consists of a bottle holding between five and twenty cubic centimeters, covered with a good qual- ity rubber cap through which the needle may be plunged and the appropriate amount aspirated. (Figs. 43 and 44.) Little bottles containing one cubic centimeter each and corked with a minute rubber cork, will frequently modify 168 TUBERCULIN AND VACCINE Proper care ^ act j ve p r i nc ipl e of the vaccine. I have seen the pre- of vaccines. * cipitated bacteria cling to the cork when pulled out, even after vigorous shaking, if the box containing the bottle had been placed upside down for a length of time. Care of Vaccines. Vaccines should be kept in a dark place. They should be kept in a cool temperature, prefer- ably in an icebox. They are never to be used when the color changes and the liquid begins to assume a brownish hue. Stock Vaccines A stock vaccine is a vaccine that is derived from an An autogenous organism not taken from the lesion to be treated. The vaccine general notion of a stock vaccine is that it is manufac- becomes a stock vaccine tured and put up for commercial sale by some concern deal- Tsi^uar ing i n biological products. This conception entirely over- infection in looks the fact that any autogenous vaccine is a stock vaccine a different . . 7 individual. when used on another individual suffering from an infection caused by the same bacteria. Such a stock vaccine coming as it does from an infection which we have handled, can be labeled with a short description of the case it was derived from. These descriptions can serve to subdivide our vaccines of the sanie organism into various In the forms of infections caused by the same organism. Thus we manufacture are a ^j e not on ] v f o h ave stock vaccines of certain bacteria, of a stock * vaccine, the but even in a. general way to obtain stock vaccines of differ- ^"obtain^d ent strains of the same bacteria. In that way, we can utilize resembles the our ] e f t-over autogenous vaccines as excellent stock vaccines strain of the . causative for similar conditions. Whether gtock vaccines are the left- oft^e'r k'wm over autogenous vaccines from other patients, or those sold prove effective, on the market by proprietary concerns, there can be no doubt about their therapeutic value. It is difficult to compare with accuracy the relative value of stock and autogenous vaccines. But a stock vaccine is effective in a sufficiently large percentage of cases to justify its use before an autogenous one is made. However, there is one element in the consideration of VACCINES 169 stock vaccines which has done much to discredit their use, The use of and which we must eliminate before stock vaccines will merit has done'mw-h recommendation. I am referring to the poly-vaccines put ^wincrf up for the market. The practice of poly-pharmacy, except va <=c'nes '" in ia very moderate degree is at all -times to be condemned. But to apply the same principle in the matter of vaccines is indefensible. If we deal with an infection which is caused by more than one organism, a separate vaccine should be made of each, and administered in such proportions as the exigencies of the case may require. Immunotherapy depends for its success upon a fair judg- ment of the immune response ; and how are we ever to learn to estimate the effect of vaccine therapy, if we are to use a multitude of different bacteria with the hope that one of them will produce the desired effect. I have gone into great detail on the subject of bacterial diagnosis because of the importance of knowing the enemy with whom we are dealing. For a thorough understanding of our enemy is the first esential in effecting his conquest. Why, then, grope in the dark with the use of vaccines? If, for instance, we are dealing with a staphylococcus infec- tion, why use a colon or a streptococcus with it? Again, supposing that we have with a staphylococcus a colon infec- tion ; by the use of a poly-vaccine consisting of staphylococ- cus and colon mixed, the colon responds so much more easily to vaccine treatment, that a radical increase in its dose would be not only useless, but even harmful ; and still, such radical increase will have to be made along with the necessary increase in the staphylococcus. I heartily recommend stock vaccine; and the polyvalent Polyvalent product as put out by the better known manufacturers is a re to be excellent. But these vaccines should be sold onlv in separ- c mmen d d only when put ate containers of sufficiently high concentration to make it up in separate i -11 i , i containers. unnecessary to. give a bulky inoculation when mixing two or more bacteria in case of multiple infection. It is for the physician to judge when to mix the vaccines 170 TUBERCULIN AND VACCINE The mixing of the various bacterial vaccines in the treatment of a multiple infection should be done by the physician alone, as he is the only judge of the dosage required. The advantages of autogenous vaccine over stock vaccine: are: 1 It is always of the same strain of bacteria as the infection. 2 It is always fresh. and the quantity that should be used of each. Happily, the proprietary concerns are now putting out vaccines of individ- ual bacteria and of high concentration ; so that the physician can have a container full of from ten to twenty cubic centi- meters of each bacteria on hand. And 'after a careful diag- nosis of the causative organism or organisms, he can draw into his syringe the proper quantity from each container as the case may require, and inoculate his patient with the mixture. In that way he will know what he is using. Sub- sequent smears, cultures or laboratory examinations will guide him as to the continuation or the elimination of any one of the bacteria that he has been using in the treatment of the infection. At the same time, he will not be treating the patient with a vaccine of all the bacteria at once, but will have the choice of administering a vaccine of one bacteria after another, a practice which will be found especially valu- able and illuminating in mixed infections in tubercular sub- jects. The treatment of a tubercular condition offers a suf- ficient length of time for such practice. Xot only will the serial use often remove the necessity of using a vaccine for other bacteria besides the principal one he has chosen to begin with (the discovery will often be made, that the other bacteria merely kept company in a fungoid form), but it will also afford an opportunity for an experience in vaccine therapy that will more than repay for the trouble. Autogenous Vaccines An autogenous vaccine is a vaccine made of bacteria grown from a Culture taken from the infection that is to be treated. An autogenous vaccine has the advantage over a stock vaccine by being perfectly fresh. And an autogenous vaccine is not only a vaccine of the causative organism, but of the particular strain of that organism that is causing the infection. Bacteria, like all living things, are influenced by environment as to their finer physical manifestations, no two individuals are exactly alike, no two infections are ever VACCINES 171 exactly alike even though caused by the same organism. Since the influences upon the growth and physical condi- tions of the bacterial organisms differ, the same bacteria from lesions in different individuals must differ in some re- spect or other. The result is a variety of strains in each form of bacteria. Probably this minute difference is of no consequence as far as the specific mechanism of defense which they stimulate is concerned. However, this minute difference may be cumulative and in the process of evolu- tion a later strain may slowly acquire such different charac- teristics that it will exert a specific influence upon the de- fensive mechanism. And it is under such circumstances that a stock vaccine, although of the bacteria in demand, may differ essentially from the causative organism in its antibody stimulation. Even a polyvalent vaccine, although composed of many strains of the same bacteria, may altogether have missed the particular strain required, or may contain so few bacteria of this particular strain, that it is not sufficient to produce the desired effect. The variation in strains is best illustrated in the strep- Especially in tococcus which offers an opportunity to see the varied out- thecaseof streptococcus ward manifestations of the infection it produces, although s it necessary the temperature curve and the general constitutional effects vaccine of the may be similar. Thus it may produce a streptococcus septi- same s * rain . cemia, or an erysipelas; at another time we may have .an causing the acute arthritis, scarlatina, etc. These strains of the strepto- coccus may vary so distinctly that we have given them dif- ferent names according to their physical manifestations, as for instance: the streptococcus viridens, streptococcus hemo- liticus, streptococcus erysipelas, streptococcus ficalis, etc. At the present time, we can obtain stock for any one of these particular strains ; but to make a diagnosis of the strain at hand, in order to be able to specify the stock we are to use, we must in many instances employ the help of a labora- tory. It might therefore be wiser to utilize the laboratory 172 TUBERCULIN AND ^ 7 'ACCINE for the making of the autogenous vaccine since the main reason for the employment of the stock is the fact that a great many physicians, especially in the small towns, have no laboratory within convenient reach. The expense item is no longer to be taken into consideration since the cost of making autogenous vaccines ihas greatly diminished in the last few years, and many State laboratories are furnishing them free. Of course, haste must not be an excuse for choosing stock vaccine; for where there is the necessity for haste, there is Manufacture always the greater necessity for accuracy. We can, however, of bacterial administer stock vaccine pending the making of the auto- vaccine, stock or genous vaccine. theiels delay" ^- n OI> dering a vaccine, we (must remember that in its between taking manufacture the more the bacteria retain of their charac- the culture v i i i i -i from the teristics, both physical and morphological, the greater the thl'compietion therapeutic value of the vaccine. It is therefore necessary of the finished to place the inoculated culture tube at body temperature as product, the ... ,. M , . -, 111 more active soon alter inoculation ;as possible in order to enable the mak- ing of the subcultures twenty-four hours later. Longer growth of the original culture may modify the causative organism by too long a contact with the products of meta- bolism of the other organisms which might be growing v in the same culture tube through accidental contamination. In making subcultures, we must remember that the more The more concentrated the vaccine, the smaller the bulk for each inoc- thev^cTne, dilation. Thus sufficient subcultures should be made in the smaller is order to make sure that there is sufficient growth for a high the bulk to be . . inoculated. concentration without the necessity for longer growth than twenty-four hours. In short, the less time that intervenes between the original inoculation of the culture tube and the completion of the vaccine, the better the vaccine will be. CHAPTER IV TREATMENT OF MIXED IXFECTIOXS It is best to consider mixed infection apart from the classification: tubercular process when dealing with the use of vaccines in infections: its treatment, and in so doing classify the infections into *' ^"Jne two distinct groups : the acute and the chronic. The sub- a Chronic .,,-,,-,. Infections. acute group need not be separately considered when dealing with infection in relation to immunotherapy, for the treat- ment is the same for the sub-acute as it is for the chronic. However, the acute form is best subdivided into two groups : the febrile and the afebrile. Mixed respiratory infections have to be considered under a special topic (Part III, Chapter V) as their treatment differs somewhat from the treatment of surgical infections. Acute Mixed Infections Acute Febrile Mixed Infections. From the nature of things as they hold true in acute febrile infections, one would assume that vaccine would be useless in such condi- tions. This being essentially a treatise on tuberculin treat- ment, we cannot go into the theories and detailed descriptions of conditions existing in febrile affections to refute the fre- quent assumption that vaccines are useless and even danger- ous in these conditions. But for the purpose of avoiding unintelligible gaps in this important subject, I shall simply add the following remarks to what has already been said in the theoretical part of this book : Vaccine in the quantity administered for the purpose of vaccines .-- , .,.. T. do not add treatment is not toxic, hence we do not add toxins to the toxicity to the body which is already saturated with toxins." Vaccines indlvldual - merely stimulate antibody formation at the site of inocula- tion even in the presence of a general infection. And al- though fever indicates a maximum amount of resistance, 174 TUBERCULIN AND \ T ACCINE forming a condition unfavorable to bacterial growth, it is true, nevertheless, that we have periods of lowered tempera- ture between the heights of the curve, representing periods of exhaustion. The period of exhaustion forms a condition entirely favorable to bacterial growth, during which the antibodies coming from a new source can do much to hold the infection in check. Vaccines Thus if we will consider the administration of vaccine stimulate the formation of in febrile infection as an aid to the natural protective mechanism, and if we mean to bring that aid when it is needed, in other words, if we are to gauge the administra- tion of vaccine so that its maximum effect will come during the periods of depression, we shall succeed in holding the enemy in check during the exhaustion period. To be more exact, the vaccine should be administered The relation about an hour or two after the height of the temperature administration curve for the day has been reached. Thus it has the greater curvr PeratUre l jart of twenty-four hours to exert its influence before the next temperature peak is reached. The immune response usually occurs within six to twelve hours after an inocula- tion. A supply of antibodies will thus be provided during a period in the temperature cycle when the patient's own resistance is at the lowest point. The influence of the vaccine will then be noticeable on the following day's temperature cycle. A (minimum amount of time, therefore, need elapse before we shall know whether this dose and the following dose of vaccine was effective or not, for if the dose happened to be insufficient, there will be no reduction in the temperature peak the following day, and a second inoculation should be given an hour or two after the height of temperature has been reached. What is true with regard to the time of administration is also true of the intervals between inoculations. The in- guide to the tervals have to be properly gauged to get the best results. Here again, by means of the temperature curve, we are able to judge the intervals most accurately. Once a temperature TREATMENT OF MIXED IXFECTIOXS 175 curve has been reduced by vaccine, we are able to wait for the next dose until the temperature begins to show, by a tendency to recur, that the effect of the previous dose is wearing off. jFrom here on, the intervals between the inocu- lations should be equal to the length of time between the one injection and the day before the recurrence of temperature took place. DOSAGE Bacteiia Beginning Dose Amount of Increase Streptococcus 25 million 10 million ( Albus Staphylococcus -s Aureus 100 million 25 to 50 million I Citreus Colon Bacillus 50 million 10 to 25 million B. Pyocyaneus 100 million 25 million In acute febrile infections we do not often deal with vaccines for more than one bacteria beside the tubercle bacillus. A simple multiple acute vaccine will therefore suffice in the treatment of such an ' infection. However, if more than one organism is found to be the cause of the infection, it is better to have a separate vaccine for each. For example, if a streptococcus and a colon are found, the proper dose of each can be mixed in the syringe and administered in one injection. It is best to treat the acute mixed infection and to ignore vaccine treatment in the tubercular process until the temperature has come down relation to to normal. That holds true whether the infection is present tuberculm . A treatment in before tuberculin has been administered, or whether it occurs febrile acute during a course of tuberculin treatment. In the latter case, the interruption of the tuberculin treatment cannot mate- rially affect the tubercular process, as acute febrile infec- tions do not last long, especially when treated) with vaccine. Once the temperature has come down to normal, tuber- culin administration may be resumed even though there still remains the indication for further vaccine treatment. We must, however, gauge our vaccine inoculations so that they fall at least twentv-four hours before tuberculin is adminis- 170 TUBERCULIN AND VACCINE 3 C C C a (* o 3 oj ,a o-t-j 5 >-^ p tf g (B_0-23 ~*f aS2 tOffi. - 71^ 3 4J g if 5^ 5 a^*f el a> o jd o u TKEATMENT OF MIXED INFECTIONS 177 tered, or forty-eight hours after tuberculin was administered. The administration of vaccine at the same time or too near the tuberculin administration niight interfere with the inter- pretation of the tuberculin reaction. Before leaving the subject of acute febrile mixed infec- The correct tion, I must emphasize the importance of accurately differ- between entiating between a febrile condition brought about by a mixed infection temperature sudden activation of the tubercular process, and a febrile and a condition brought about by a mixed infection. In an acute temperature condition caused by the tubercle bacillus, the uselessness of > essential, a vaccine made from an avirulent organism is apparent. On the other hand, much harm can result from a failure to institute the proper vaccine treatment against an acute febrile infection occurring during a course of tuberculin treatment by attributing the temperature rise to an exten- sion of the tubercular process, or to a tuberculin reaction. Acute Afebrile Mixed Infections. When an infection is acute, as evidenced by the acute local manifestations, and still produces no constitutional manifestations such as tem- Definition, perature with its accompanying symptoms, we have one of two conditions. Either there is an acute inflammation bal- anced by a high degree of resistance, with absorption of the inflammatory, bacterial, or cellular products, in quantities too small to cause constitutional symptoms ; or else there exists a point of exit for the inflammatory products other than by means of the circulation. This exit may be drain- age through an incision, or suppuration ; or through sinuses or fistulas; or through natural channels, such as the ureter, urethra, bronchial tubes and so on. The following dosage has been found satisfactory in most instances: DOSAGE Amount of Bacteria Beginning Dose Increase Streptococcus 50 million 10 to 20 million j Albus 1 Staphylococcus A Aureus V 150 million 25 to 50 million ( Citreus J 12 ITS TUBERCULIN AND VACCINE Colon Bacillus 50 million 25 million B. Pyocyaneus 100 million 25 million The time of administration is no factor in the treatment of afebrile conditions, as there are no periodic fluctuations between the infection and the patient's resistance. How- ever, as regards intervals, a measure of accuracy must be applied. But not having the guidance of a temperature Time and curve, we must be governed entirely by subjective or objec- intervai of ^ ve symptoms. Thus if there is no improvement in forty- administration eight hours, the patient should be reinoculated if the mini- mum dose was used in the first place. ,The intervals may be determined after improvement has taken place, by waiting with further treatment until a tendency for the recurrence of the symptoms appears. The vaccine treatment is then continued without again waiting for the recurrence of symp- toms, but by administering the reinoculations one day before. The objective and subjective signs which act as guides for the determination of intervals and effects of the vaccine treatment in general are : pain, tenderness, swelling, redness, increased or diminished motion, the character and quantity of the inflammatory discharges, and so on. If a reaction occurs immediately after an inoculation, as evinced by increased symptoms (negative phase) the vac- Production c ^ lie treatment should be discontinued until all signs of the of a negative reaction have disappeared. Usually, there is a period of phase should . * n , . , . , . be avoided. improvement following such a reaction, which is more pro- nounced than the improvement following treatment, without the production of a negative phase. However, we should not purposely produce a negative phase for that would tend to the production of a permanent negative phase with its attendant dangers. The dose of vaccine following a tran- sient negative phase should not be increased; however, it need not be diminished, as it is unusual for the same dose to produce a negative phase more than once. And when a negative phase does occur, it will be transient and therefore beneficial. TREATMENT OF MIXED INFECTIONS 179 After the subsidence of the acute symptoms it is advis- Conclusion -i of vaccine able to continue the vaccine treatment for a time, in order treatment to inaintain the immunity gained against the mixed infec- tion. For this purpose it is sufficient to administer one dose of vaccine a week, continuing with slight increase for sev- eral weeks after all traces of infection have passed. The element of time is frequently just as important in cases of afebrile conditions as it is in cases of febrile mixed stock or infections. So that it may be advisable to use simultane- vaccfnes US ously a vaccine for each of the organisms found. However, in the majority of instances, (it is practicable to use ia vac- cine for the preponderant organism first, and only then con- sider vaccines for the remaining organisms if the treatment with the first vaccine proved unsatisfactory. The tuberculin treatment can be continued without inter- ruption during the vaccine treatment of acute afebrile mixed vaccine infections. However, if the mixed infection is of such an in relation acute nature that rapid extension of the disease is threatened, * t " berc ' 1 l m ' treatment in and if shorter intervals than one week are indicated for the afebrile vaccine inoculations, one treatment a week with tuberculin would be sufficient until the mixed infection is under control. The vaccine treatment of mixed infections in tubercular conditions has been observed to be more successful in tuber- culin treated patients than in patients not treated with tuber- culin. This may find explanation in the fact that tuberculin reaction is . < i i * *" aid to produces a hyperemia at the point 01 inoculation through vaccine the focal reaction, offering greater facility for the ready treatment - access of the artificially stimulated immune products, to the organisms causing the infection. Chronic Mixed Infections Chronic infection from the standpoint of immunology is Definition. a state of equilibrium between the onslaught of the invading organism and the defense of the host. This equilibrium is maintained by means of various mechanisms. On the part of the bacteria, the failure to advance may be due to a los? ISO TUBERCULIN AND VACCINE of virulence, or to an inability to penetrate the fibrous bar- rier which the host has built around the infection (incap- sulation). The formation Qn the part of the host, a failure to entirely overcome of chronic . . . infections. the invader may be due to an insufficient immune response; to a mechanical obstruction to circulation caused by a high coagulability of the serum carrying the defensive substances, thus clogging the tissue spaces and impeding the further arrival of antibodies; and to an insufficient carrier of the products of the immune response to the invading organism. The last is due to the occurrence of anemia instead of hyper- emia at the point of infection. This anemia may be brought about either by a state of the blood, or by mechanical obstruc- tion to the circulation at or near the point of infection in the form of a defensive capsule to stay the advance of the infection. Thus the very instrument of defense (defensive capsule) may become so formidable that connective tissue cannot penetrate through it. The formation of a permanent canal (sinus or fistula), or cavity, or both, takes place in which the invader can live and multiply in comparative security shielded from the immune bodies of the host. This deadlock between infection and resistance may be maintained by a number of other causes which we need not discuss in further detail at this time. [But it is necessary to have at least a cursory understanding of the. elements of chronic infection in order to effect its final elimination. chronicity Xowhere is chronic infection so chronic as in tubercular pronounced in bone diseases, for the tubercular process tends to form cavi- ties in which the infective material gathers, causing the for- mation of fistulas through which the contents of the cavities are discharged. Where the equilibrium between the resistance of the host and the virulence of the invader is the sole cause of chronic infection, vaccine alone is sufficient to cure such a condition. For with vaccine, we are able to add sufficient antibodies to those naturally formed to break the deadlock TKEATMEXT OF MIXED INFECTIONS 181 in favor of the host, and at once accomplish a cure. But The treatment . , ,, ff. . l pathological where other elements aside irom the msumcient immune changes response are the cause of the chronic infection, such as fis- t^chrontcit 11 * tulas and cavities and so on, we must look for appropriate must be 1ln .i . T i i r> -i T considered methods besides vaccines to accomplish the final eradication apart fr om of a chronic process. Such methods will be described under ^e treatment * of the Bone Cavities, Sinuses and Fistulas. infection. The dosage, as well as the increases, are somewhat higher in chronic conditions than in acute conditions. DOSAGE Amount of Bacteria Beginning Dose Increase Streptococcus 100 million 25 million C Albus ] Staphylococcus < Aureus V 200 million 50 million, (Citreus J Colon Bacillus 100 million 25 to 50 million B. Pyocyaneus 150 million 25 to 50 million One treatment a week is most convenient and usually sufficient, but it must be so timed as not to interfere with the determinations of the bi-weekly inoculations of tuber- culin. A chronic infection in a tubercular subject constitutes a suitable condition for the study of the mode of action, and Vaccines of the effects of vaccines. The character of the cases, and mul the length of time required for a course of tuberculin treat- chronic ^ m infectionS ment offers a long enough period for any method of vaccine treatment we may find appropriate to apply. Thus I have found that in the long run the use of vaccine against one organism at a time in cases of multiple infection, not only produces better results but offers the best conditions in which to determine the exact role which each organism plays in mixed infection. For instance, if we have a streptococcus and a staphylococcus albus and a staphylococcus aureus in a mixed infection, by making an autogenous vaccine for the streptococcus or by using a stock streptococcus vaccine, we 182 TUBERCULIN AND VACCINE can study by culture and by smear the effect of these vac- cines on such infections. If, after the streptococcus vaccine has been used for a reasonable length of time, and if the streptococcus disappears from the discharge without producing any appreciable effect either quantitatively or on its consistency, we can be reason- ably sure that the staphylococcus aureus or the staphylococ- cus albus or both have been active in the formation of the infection, and will require rthe specific vaccines for their irradication. If, however, the discharge thins and becomes sterile after the use of the streptococcus vaccine, it is at once evident that the staphylococcus merely existed in the discharge in a parasitic form, or formed a coincident surface infection during the taking of the cultures while the real offender was the streptococcus alone. By this method, besides saving time, expense, and trouble for the patient, we obtain a grasp upon vaccine therapy that no other method offers. Of course, the necessity of working with cultures and smears may appear too complicated a task for the busy gen- eral practitioner. However, the whole matter may be made very simple and may even add another element of interest to his work. The growing of cultures may be accomplished by the simple procedure described in Chapter II, Part III. Smears may be made on ordinary slides (which can be easily ob- tained) by first placing a drop of water on the slide; the material to be examined is stirred up in this drop of water and spread in a thin film, allowed to dry in the air, and fixed in the flame. The process of staining is still simpler. Loefler methylene blue is all that is required. A few drops are placed on the smear for one minute, then rinsed off with ordinary tap water, and after the slide dries the smear is ready for examination under the microscope. To make matters still simpler, nature has endowed the pyogenic bacteria with very easily distinguishable features. TREATMENT OF MIXED INFECTIONS 183 For example, the streptococcus is easily recognized by its- chain formation; while the staphylococcus grows in groups. The albus, aureus, and citreus can be distinguished from their different appearances in the culture tube. The albus is white, the aureus a golden yellow, and the citreus a lemon yellow. And the colors are so distinct that there is no room for doubt as to their identity. (Chapter II, Part III.) CHAPTER V MIXED INFECTIONS IN PULMONARY TUBERCULOSIS Mixed Mixed infections in pulmonary tuberculosis .differ so respiratory radically from mixed infections in other processes, both in conlLTs^oT tne ^' pathological forms and in their symptoms, that it is w j se f o g O f n to a little more detail on the subject rather than and catarrhal . . m . processes. to include it under the general heading of mixed infections. As was stated in the preceding chapter, a mixed infection merely means an infection [with an organism, or organisms, superimposed upon and helping to continue the tubercular process. It rarely assumes an unusual form. In respira- tory conditions, however, the mixed infection organism may not only exaggerate the usual symptoms of pulmonary tuber- culosis, and animate the tubercular process, but may produce symptoms entirely apart from the tubercular process. Such infections may be sufficiently acute to be more dangerous to life than the tubercular process itself; they may upset all the beneficial' results obtained with tuberculin, and render the condition hopeless. Weather Again, we must bear in mind what a tremendous influ- and c'atarrhai ence weather conditions have upon a tubercular process in processes in the lungs ; for the intimacy that exists between the various the upper air jf i passages exert parts of the respiratory system is self-evident. An acute i^nutncTupon r hinitis may alter the aspect of a tubercular lung condition, pulmonary and a streptococcic sore throat ,may do for the pulmonary tuberculosis. , . process what measles will do in any tubercular condition in the child. The following In a condition of mixed infection in pulmonary tuber- three distinct ,... nr> i i situations for culosis it is not sumcient merely to make a vaccine of the offending organisms, but we pmust consider its application exi st: with reference to three distinct situations: First, the use of vaccine in co-existing mixed infections which add to the MIXED INFECTIONS IN PULMOXAKY TUBERCULOSIS 185 chronicitv of the process as they do in all other forms of mixed tuberculosis: second, an acute or subacute infection co-exist- infections; ing with the tubercular process, interfering with or nullify- subacute ing entirely the immune response to tuberculin; third, and "f*"^ 1 .. . most important, the use of vaccines in prophylactic immuni- ? Prophylactic 1 immunization zation, during periods of the year when catarrhal inflamma- against preva- tion, such as influenza, bronchitis, etc., are prevalent. It is ideal when dealing with so complex a problem as immunization in respiratory mixed infections to have the patient in bed under constant professional supervision, with a well equipped laboratory and trained laboratory assistants, For practical to make daily observations as to the effect of the vaccines thTmost ' injected, and of the change in the organisms present. The P rominent bacteria need percentage of physicians who have such facilities is so small be considered that we cannot even dignify their number with the name of t l^"r^ minority. Those who have these facilities, and are taking advantage of them, are rendering a great service by clearing many of the complexities connected with the subject, making it possible for us to utilize their experience to some extent in our practical application, however limited the field may yet be. For the vast majority of physicians who do not have these (facilities, it is fortunate that we are easily able to find at least the most important organisms by simpler methods, and treat the patients with a fair measure of success. Since this book is intended as a guide to the utilization of the immune response within the limitation of practical application, I shall avoid enlarging upon methods which can be carried out only by means of modern laboratory facilities. The number and variety of bacteria that may be found in respiratory secretions is of necessity large because of the easy access that any bacteria has to any part of the respira- tory tract. Xot only are the canals open, but we directly invite the entrance of these organisms by inhalation, by the partaking of food, and* by the deep recesses that can harbor bacteria and allow them to grow. Yet, not all bacteria found TUBERCULIN AND VACCIXE Even in the presence of a large variety of bacteria, treatment for the strepto- coccus, penumococcus, and the m. catarrhalis is sufficient in most cases. in the respiratory tract, even during disease, are pathogenic; and when we have an infection in the respiratory tract it is very difficult to determine which of the organisms are at fault. However, some of them are commonly at fault. In the treatment of respiratory infections existing in a tubercular individual, we must be content to make a vaccine of one or more of the easily recognized and easily cultivated bacteria that we find. Fortunately this will embrace a large enough class of cases to make it worthy of trial. The variety of organisms at fault is relatively small in cases of mixed infections in tubercular lungs. We find by experience that the streptococcus in a tubercular lung is most often concerned with the production of the added in- fection, whereas the staphylococcus is found to be the most frequent offender in infections in a non-tubercular lung. By using an autogenous vaccine of the streptococcus found in the sputum of a pulmonary tubercular patient, we very often clear the mixed infections to such an extent that it need not be reckoned with (any further in the treatment of the tubercular condition. The staphylococcus is of course a frequent offender. The pneumococcus takes the third place. Less frequently do we Jiave to deal with the micro- coccus catarrhalis, the influenza bacillus, the Friedlander bacillus, and the micrococcus tetrogenus, except in prophy- lactic immunization during prevalent catarrhal infections. I have left other organisms out of consideration, because of the difficulty of isolation, and the frequency with which they disappear from the sputum after using the vaccines against the other organisms. Chronic respiratory mixed infections are of two varieties: i. Infections superimposed Chronic Respiratory Mixed Infections The chronic infections form the greatest majority of mixed infections in pulmonary tuberculosis, and in their consideration we must recognize two distinct types. The in- fection which implants itself upon a tubercular area as it does in bone and gland tuberculosis ; and the catarrhal infec- MIXED INFECTIONS IN PULMONAKY TUBERCULOSIS 187 tion which prepares the soil for the tubercle bacillus. The former requires treatment only when we find that it aggra- vates the tubercular infection or interferes with the benefits derived from the tuberculin. The mere finding of bacteria in the sputum is pot sufficient a reason to consider the use of vaccines necessary. However, we have a more difficult problem to deal with in the treatment of primary mixed infections which resisted the process of natural immunity and treatment for a great many years, and which produced trauma in the lung, and attracted the tubercular infection in the lung in the same manner as direct trauma attracts the tubercle bacillus in a case of bone and joint disease. Here we must not lose sight of the various pathological changes that many years of catar- rhal infection have brought about in the lung and bronchial tubes. These changes must be reckoned with in our expec- tations as to the results to be obtained from immunotherapy. Mixed Infections Which Follow Upon a Tubercular Process. The number of bacteria that may implant them- selves upon a tubercular process in the lung is very large and varied. The direct communication between the nose and mouth and lungs makes this possible. Fortunately not all the bacteria are pathogenic and not all of the pathogenic bacteria that find lodgment in the tubercular lung get beyond the saprophitic form. Even those that do become virulent and help in the pathological changes brought about by the tubercular process naturally become extinct during the heal- ing process of the tubercular infection, and so require no special attention. However, during the treatment of the tubercular condi- tion, any of these pathogenic bacteria may get deeper lodg- ment and produce symptoms which will cause a drain upon the system. The progress against the tubercle bacillus will thus be interfered with unless treatment aiming to eradicate the mixed infection is instituted. Since the streptococcus is the most frequent offender in pulmonary mixed infec- upon the tubercular process; 2. Primary infections which created the traumatic condition, and which attracted the tubercle bacillus. The tubercular process in the lung is particularly prone to mixed infection. 188 TUBERCULIN AND VACCINE tions, a vaccine made of the streptococcus will often control all the annoying symptoms that may arise to interfere with the tuberculin treatment. Frequently, the catarrhal types of bacteria become just as annoying; thus the micrococcus catarrhalis, and the pneumococcus, and other bacteria occa- sionally demand our attention. In order not to deviate from the practical purpose of this book, I shall not go into detail here concerning the more infrequent infective organisms, especially as such bacteria are isolated and grown with diffi- culty. The streptococcus vaccine will cover so many cases of mixed infection that by means of this vaccine alone much can be done in the treatment of a mixed infection super- imposed upon a purely tubercular process in the lung. Primary mixed Mixed Infections Which Act as Fertilizer for the most difficult Tubercular Process. Primary mixed infections offer a more difficult task for the physician. Here we have a chronic respiratory infection as the primary pathological process the process acting after the manner of trauma in hone and joint infection by establishing a localized loss of resistance, while the bacteria act as fertilizer for the growth of the tubercle bacillus when once the tubercle bacillus lodges in the respiratory tract. A distinction By caref ul differentiation between the various signs and be made symptoms, we can distinguish those symptoms which are caused bv the mixed infection, from those due to the tuber- symptoms produced b y cular process. Unless this differentiation is made, the phys- s ^8' ns these conditions which are usually spread over those produced onc or even over ^h lungs, will produce the impression of by the mixed infection. an extensive tubercular process, whereas in truth only a be- ginning tubercular infection exists. It therefore happens that during any treatment of the mixed infection which proves effective, the tubercle bacilli may disappear from the sputum, leading to the assumption that a cure of the tuber- cular process has been accomplished. At this stage the patient is usually discharged from further observation, although it is well known how readily MIXED INFECTIONS IN PULMONARY TUBERCULOSIS 189 a chronic respiratory infection will return. When the Treatmentof the tubercular slightest recurrence of the chronic infection takes place the process is , . . , ., .,. often relaxed tubercular condition recurs because the hypersusceptibihty on account still remains. In this class of cases we have the great army "nterpre'tation of sufferers who are not alarmed at their condition because of the dis ~ appearance of the long standing of their infection. They take their con- of symptoms dition seriously only when tubercle bacilli are found in their due to the" sputum. A change of climate, and more favorable hvgienic, m ' xed " ' infections. dietetic treatment, quickly improve these patients. They then return to their regular habits and occupations, only soon to fall victims to a recurrence. The chronicity of the mixed infection thus goes hand in hand with the chronicity of 'the tubercular infection, the pendulum swinging back and forth between apparent cure and evident recurrence until they finally succumb to the slowly progressive tuber- cular infection, or to an acute exacerbation of the disease. The tuberculin treatment of these patients we have already discussed in ^Chapter VI, Part II. If we add vac- cine treatment for the mixed infection, we are able to raise the resistance of these patients to a. degree that will permit a thorough eradication of the tubercular process. Since tuberculin also removes the hypersusceptibility, a recurrence is thus in a great measure prevented. Of course the ideal treatment is a combination of immunotherapy with climatic treatment, but when circumstances will allow only one of the two methods, immunotherapy must be chosen. The increasing of resistance through immunotherapy in spite of the patient's surroundings will produce permanent results, whereas a return to former conditions after an improvement gained through a change in climate will prove more rapidly detrimental than when those conditions contributed to the production of the original condition. The chronic infections which prepare the soil for the advent of the tubercle bacillus may be any one of the chronic infections that exist in the respiratory tract, such as chronic bronchitis, bronchial asthma, unresolved pneumonia and all 100 TUBEECULIX AND VACCINE catarrhal conditions that form pathological changes in any of the respiratory passages. The bacteria that are most at fault here are the streptococcus, micrococcus catarrhalis, the pueumococcus, m. paratetrogenus, Friedlander B., bacillus influenza, staphylococcus albus and aureus. The medical Treatment. The medical treatment and the hygienic respiratory dietetic treatment must be carefully carried out in chronic mixed mixed infections, whether the mixed infection was the cause infections is important. of the tubercular process, or came as a result of it. The indiscriminate use of drugs should be avoided especially in the case of narcotics or creosote. Creosote, when wrongly used, is capable of a great deal of harm, and yet, should not be dispensed with, for it is equally capable iof a great deal of good when applied in the proper condition and in the proper dosage. We should familiarize ourselves with the physiological action and proper indications for the use of this drug before prescribing it. The vaccine The dosage of vaccines is the same in all chronic condi- tions. Fifty million of the streptococcus should be given as a beginning dose, increased by about twenty million for the following three or four doses and if there seems to be no beneficial effect as would be noted by a decrease in amount, or a change in character of the sputum, or by an evident decrease of the streptococcus in the sputum the last dose should be doubled and then continued' at the same rate of increase as before. The micrococcus catarrhalis and B. Friedlander best administered in doses of twenty-five million, increased 'by five or ten million for each of the subsequent four 'or five doses and if need be, the fourth or fifth dose can be doubled to get a more positive effect. The beginning dose of the m. paratetrogenus should be fifty million, increased by from ten to twenty million at each subsequent dose. The pneumococcus and b. influenza should be adminis- tered in the same dosasre as the m. catarrhalis. MIXED INFECTIONS IN PULMONAKY TUBERCULOSIS 191 The staphylococcus albus and aureus should be admin- istered in a dose of two hundred million in the beginning, with subsequent increases of twenty-five to fifty million, with the same doubling of the fourth or fifth dose if it should be necessary. TABLE OF DOSAGE Streptococcus M. Catarrhalis B. Friedlander M. Paratetrogenus Pneumococcus , B. Influenza | Albus Staphylococcus < ( Aureus Beginning Dose 50 million 25 million 25 million 50 million 25 million 25 million Increase 20 million 5 to 10 million 5 to 10 million 10 to 20 million 5 to 10 million 5 to 10 million 200 million 25 to 50 million Before tuberculin treatment is instituted it is advisable Treatment of to treat the chronic infection with vaccines until it is under infection before control. About three or four weeks of treatment will usually tuberculin * treatment. suffice to get the chronic infection under control, and then tuberculin treatment should be instituted. However, we must make certain that where vaccine treatment is instituted before the tuberculin treatment, the acute condition is not due to the tubercular infection. The tuberculin treatment should not be delayed in cases where the tubercular process has produced a great deal of wasting. In case of a multiple mixed infection and if the patient is in fair physical condition, it is best to administer a separate vaccine of each organism on different days rather than to treat the patient with all of the vaccines at the same time. For the purpose of illustrating, let us assume that the streptococcus, the m. catarrhalis, and the pneumococcus are the principal offenders. The streptococcus vaccine can be administered on Monday, the catarrhalis vaccine on Wednesday, and the pneumococcus vaccine on Friday. A more clear cut immune response can thus be obtained, and 192 TUBERCULIN AND VACCINE a more accurate observation can be imade of the effect of each vaccine. In chronic mixed infections which become implanted upon a tubercular area, vaccines need not ibe used until the tuberculin treatment has been administered for two or three Treatment of months. The reason is the same as for the application of inf'eTtlon 6 vaccines before tuberculin in primary mixed infections. The during improvement of the primary condition through any agency treatment. will exert a beneficial effect on a secondary process. Through the treatment of the tubercular process which is here pri- mary, the mixed infection process may be so favorably in- fluenced that it may require no treatment. The local hyper- emia produced by the tuberculin focal reaction is sufficient tn overcome the mixed infection, especially as the chronicity of the process has robbed the causative bacteria of their virulence. However, should the mixed infection persist in spite of improvement in the tubercular process, its treatment should be undertaken by the use of a vaccine against the most promi- nent organism found in the sputum. Later, a vaccine against each of the other organisms that persist in the sputum should be used, if no improvement has taken place from the pre- vious vaccine. In the same manner several vaccines may be Tried in turn until the mixed infection is no longer a factor in the production of symptoms. These vaccines should be administered once a week, and so timed that they do not interfere with the tuberculin reaction. Acute Respiratory Mixed Infections Acute respiratory infection occurring in a patient with An acute mixed pulmonary tuberculosis forms a most berious condition of infection in a / . . tubercular affairs, since an acute infection has the tendency to greatly lower the resistance of the patient to tuberculosis. When acute infection occurs in the same organ, it not only raises the hypersusceptibility to a marked degree, but also encour- ages a local extension of the tubercular process. MIXED INFECTIONS IN PULMONARY TUBERCULOSIS 193 So it happens that a lesion erstwhile progressing favor- ably under tuberculin treatment may be suddenly invaded by an acute respiratory infection which lights up the tuber- cular process to such a degree that it passes beyond control. Fortunately, in prophylactic immunization we have a means by which the danger of an occurrence of acute infection can be greatly minimized. But when it does occur we must unite all the resources at our command to tide the patient over the acute attack. Since vaccine forms at least as im- portant a measure as any other, it is the duty of every physi- cian to utilize it under such urgent circumstances. In dealing with acute pulmonary infections complicat- Acute mixed ing tuberculosis, two distinct (types should be recognized : the aVof'tvro acute infections which are acute exacerbations of a chronic varieties: i. Acute ex- infection, and the fresh acute infections that are epidemic, acerbations Under the former, we are dealing mainly with pyogenic infec'ticn" 10 organisms producing such conditions as pulmonary abscess, 2 - Fresh acute 1 or epidemic empyema, and pneumonic processes. Under the second class, infections, we deal mainly with catarrhal bacteria producing lacute " colds," influenza, and so on. Treatment. Aside from immunotherapy for acute con- Treatment of ditions in pulmonary tuberculosis, we can add but little to acutemi * ed " infection in the present day accepted methods of treatment. However respiratory mild the acute infection may be, rest in bed is absolutely imperative. Appropriate drugs, proper food and proper elimination are equally important. However, a wider expe- rience with immunotherapy will not only demonstrate its value as an additional aid in the treatment of acute respira- tory infections, but the reduction in the frequency of the occurrence of acute infection through prophylactic immuni- zation will become apparent. During the vaccine treatment of acute conditions it is interrupt best to interrupt the tuberculin administration while the treaYmenT process is still acute. The increased hypersusceptibilitv that during the > /J r _ treatment occurs as a result of the acute infection may bring about a of acute constitutional reaction which, being masked by the symp- 13 1'J-i TUBERCULIN AND VACCINE torn? of the acute mixed infection, would lead to a further inciease in the dose of tuberculin, and bring about a disas- trous result. After such an interruption, the tuberculin treatment should be resumed with a dose considerably smaller than the last dose previous to the acute infection. The bacteria most concerned in acute infections are: the pneumococcus, M. catarrhalis, M. tetrogenus, B. septus, B. influenza, the staphylococeus, and the streptococcus. TABLE OF DOSAGE Beginning Dose Increase The tempera- ture curve is the best guide to dosage and intervals of vaccine treatment. Pneumoeoccus M. Catarrhalis M. Tetrogenus B. Septus B. Influenza Streptococcus 25 million 5 to 10 million 20 to 40 million 10 million {Aureus ~| V 100 to 150 million Albus J 25 to 50 million In the treatment of acute infections with vaccines we have the temperature curve as, the best guide to dosage and intervals. A careful temperature record will show at the end of twenty-four hours whether the dose was insufficient, or whether an overdose was used and a negative phase pro- duced. The vaccines of all the offending organisms should be administered in each inoculation, unless the infection definitely points to one or more of the bacteria as being the sole cause, in which case these alone should be used and the reft ignored. One example is the pneumococcus : If the sputum shows an abundance of the pneumococcus, a vaccine of the pneumo- coccus will be sufficient even though other bacteria may appear in the smear; the same holds true of the influenza bacillus. However, if the streptococcus or the M. catar- rhalis appear with the two above mentioned bacteria, it can INFECTIONS IN PULMONARY TUBERCULOSIS 195 do no harm, nor can it jeopardize the beneficial effects de- rived from ; the use of the influenza or pneumococcus vaccine if we add the minimum doses of streptococcus or M. catar- rhalis vaccines. After the acute symptoms are passed, it is advisable to continue the use of the vaccines for several months at weekly or two-weekly intervals. Prophylactic Immunization Against Mixed Infections Vaccines have no better field than in prophylactic im- Prophylactic .,.,. . -, , -, immunization mumzation against mixed iniections in pulmonary tubercu- against mixed losis. We all know the importance of protecting these suf- inf ections . . plays an ferers against weather changes and against exposure to rain important and dampness. We also realize that the object in carrying j^tmelt'of out these measures of protection is to prevent a temporary pulmonary , . , . , . . , / tuberculosis. lowered resistance, which would render the individual sub- ject to a new bacterial invasion, or to an acute exacerbation of chronic infection. But what is the success of these measures ? In spite of all that is done, there are so many chances for the patient to be caught off guard, that only few escape an infection in the respiratory tract during the treatment of the tubercular condition. Prophylactic immunization greatly reduces the dangers of infection ,by raising the resistance to the bacteria to such a degree that even if it is not sufficient to prevent infections altogether, it certainly w r ill prove effective in com- bination with the usual measures of prevention. The importance of prophylactic immunization against mixed infection cannot be sufficiently emphasized. Among the greatest achievements in medicine, that brought about by prophylactic immunization stands preeminent I need but mention the prevention of typhoid fever alone, to call forth a realization of the possibilities of prophylactic immuniza- tion. The written medical annals of the present great war will contain no less a staggering array of superwonclers brought about by medical and surgical skill, than those 196 TUBERCULIN AND VACCINE accomplished by the engineer or general. And prophylactic immunization against all forms of infection will be found to have played a startling part in the formation of these annals. I say startling, because the greater part of the med- ical profession that still scoff at vaccine therapy in general, will suddenly wake up to the fact that they have been hope- lessly left behind. The following Prophylactic immunization consists of two distinct prophylactic forms: that which aims to prevent epidemic infections, and immunization ^hat ^yhich aims to prevent acute exacerbations of infections should be < f considered: the bacteria of which are present in the sputum. i. Prophylactic Prophylactic Immunization Against Epidemic Infec- immunization . it i i * , i .'' M against tions. Prophylactic immunization against epidemic miec- epidemic tions is as simple as prophylactic immunization against infection. , - typhoid, except that we have more than one bacteria to deal with. As in typhoid, (three inoculations with a stock vac- cine are administered a week apart, and in the following doses : First dose Second dose Third dose Pneiimococcus B. Influenza M. Catarrhalis ' . .,, 1 L 100 million 200 million 300 million B. Jb riedlander Streptococcus (Salivarius) A bottle of stock vaccine (holding from five to twenty cubic centimeters) should be obtained of each bacteria. A concentration of at least 1,000 million bacteria per cubic centimeter should be insisted upon, thus avoiding too bulky an inoculation for the third dose. The five bacteria need not be combined into one vaccine and administered at one time. If it is found expedient, we may divide them into two groups and administer one group on one day, and the other group on another day, keeping a record of the administration of each so that the reinocula- tions may be continued at weekly intervals. MIXED INFECTIONS IN PULMONARY TUBERCULOSIS 197 Prophylactic Immunization Against Acute Exacerba- 2 - Prophylactic . . . . immunization tions. Prophylactic immunization aimed to prevent acute against acute exacerbations of infections, the bacteria of which are present exutig in the sputum, is not quite as simple as the prophylactic chr ni c . . . . , ... infections. immunization against epidemic injections, as it requires a microscopic study of the sputum in order to determine the bacteria against which immunization is necessary. How- ever, the amount of knowledge that is required for practical purposes can be acquired without much difficulty. The organisms that need be considered in this connection can easily be distinguished after a short reference to any book on bacteriology, especially Allen on " Bacterial Diseases of Respiration." The organisms consist of one or more of the following bacteria, and should be administered according to the accompanying dosage: First dose Pneumococcus M. Paratetrogenus M. Cattarrhalis Streptococcus (Salivarius) B. Friedlander 50 million, increased weekly by 25 million One inoculation a week is sufficient, but inoculations should be continued for a longer period than in the case of prophylactic immunization where the bacteria are not present in the sputum. In the estimation of the value of prophylactic immuni- zation we must consider the length of the period of immunity that is conferred by the various infectious organisms. It is The length well known that these periods differ greatly with the differ- bacteria are ent infections. For instance, the bacteria producing measles e *^^* f conferring an confers a life immunity; in the case of typhoid, the period immunity , i , i c i i , i ii should serve seems to be about seven years ; in the case 01 diphtheria, the as a guide use of prophylactic antitoxins seems to protect for about six *r- L L ' ... immunization. weeks only, and so on through the various infections. Un- 198 TUBERCULIN AND VACCINE fortunately the length of immunization acquired as a result of respiratory infections seems to last no longer than two or three months. Therefore, it is necessary to repeat the pro- phylactic immunization once or twice during the period between September and May. For example, if a prophy- lactic immunization is administered in September, it is ad- visable to repeat the inoculations in December and again at the end of February. General Prophylaxis The disregard The consideration of prophylactic measures apart from p r o h p y ja c a t " c vaccines does not come under the province of this work, but I find that the neglect of prophvlactic measures is so fre- particularly noticeable in qncntlv a source of failure in immunotherapy that I cannot of pulmonary dismiss the subject without calling attention to its -impor- tance. The more recent adoption of prophylaxis of the This is true L not only in moil th and teeth and nasopharynx into general prophylaxis cTses buT y a ^ so Deserves more attention than it receives at the hands of the general practitioner; especially when its main obiect is seated in \ . J many public to remove common sources of reinfection. Here also we shall take into consideration the elimination of pathological processes which so frequently occur in obscure recesses and occupy such small areas that they escape the notice of the patient as well as of the physician. The consideration of dietetic measures, not only from the standpoint of nutrition, but what is more important, from the standpoint of assimi- lation, must be here included as well as the important ele- ments of rest and exercise. Attention to Elimination of Sources of Infection. One of the prin- the nose, . throat, and cipal contributions to the knowledge of medicine in the last decade has been the discovery that pathological dental pro- cesses, pathological changes in the tonsils and in the nasal conditions , ,, ,. vhich are pharynx form important factors in the production of chronic luentiy ,li se a>e, and that the elimination of these factors is essen- of mixed tial to the total eradication of chronic infections. Since tuberculosis is the most universal of the chronic infections, INFECTIONS IN PULMONARY TUBERCULOSIS 199 these pathological processes demand as much attention when they ocur in a case of pulmonary tuberculosis as in any other chronic infection. A thorough examination of the teeth and gums by a competent dentist, including X-ray examinations of the dental processes and of the roots, is a necessary adjunct to the successful treatment of tuberculosis. The bacteriological study of tonsils removed from other- wise healthy children has sufficiently demonstrated the fact that the tonsils are not only very often the source of mixed infections, but the source of the tubercular process as well. The nasopharynx, including the sinuses and antrums, is a frequent source of mixed infections. We may not, how- ever, institute indicated surgical measures such as the re- moval of adenoids, the removal of tonsils, the removal of hypertrophied turbinates, etc., until the tubercular infection has been checked. But during the treatment of the tuber- cular process we must institute such measures as will elim- inate their negative influence on the favorable progress of the disease. We often cannot dispense with the dentist in spite of the poor circumstances of the patient, but we are able to admin- ister such medical treatment for the various conditions in the nasopharynx, etc., that in these conditions we can for the time being, at least, dispense with the help of a specialist. Of course it would be ideal to have a specialist co-operate with us in the treatment of these conditions, but the majority of us deal with a class of patients that cannot afford any extra expense, and a large number of general practitioners who practice in the rural districts are beyond the reach of the specialist. A nasal spray composed of twenty grains of menthol, twenty grains of camphor, a few drops of oil of cinnamon in an ounce of liquid vaseline will do a great deal to improve the breathing and is as good a mucous membrane anti- septic as we have. Add to this a five to twenty per cent, argyrol, and our armamentarium is complete for the control 200 TUBERCULIN AND VACCINE of most of the conditions that may exist in the upper air passages. Other medicaments for local application or for internal use may be found of value for special conditions. For further detail .the reader is referred to the proper au- thorities on the subject. Personal Personal Hygiene. Personal hygiene of the patient nTifst'bl embraces daily care of the mouth and teeth and frequent insisted bathing to enlist the proper function of the skin. Let me upon. mention here that the matter of encouraging bathing is of great importance, as the fallacy exists among the laity that the bath is detrimental to the sufferer from phthisis by exposing him to colds. He should be encouraged to live under proper conditions, a clean room, proper ventilation and many other fine details that are not only beneficial from the hygienic standpoint, but help to divert the patient's mind to details not altogether bearing directly on his disease. These diversions are very helpful. I mention these very familiar points in the hygiene of the patient, not because I need to call attention to them, that is hardly necessary in view of the fact that the importance of hygiene in tuber- culosis was recognized generations ago and constitutes prac- tically the major part of the usual treatment of tubercu- losis but in order to call attention to the absolute necessity on the part of the physician to insist upon their being car- ried out. Frequently these directions for hygiene are given to the patient at the same consultation when his diagnosis is made and when the patient's mind is far from realizing their importance. Again, the patient reads and hears so much about hygiene that his very familiarity with the subject causes him to neglect it. The physician must repeat his directions and insist on absolute compliance with them, and refuse the treatment of any patient who persists in neglecting them. Dietetics. Dietetics in tubercular individuals has been a topic of controversy for many years. The varied opinions of different workers in tuberculosis have extended from rest MIXED INFECTIONS IN PULMONABY TUBEKCULOSIS 201 in bed and fluid diet to the extreme of forced feeding. I Dietetics must be believe we have at last arrived at the best possible method regulated of feeding tubercular patients. Tuberculosis is a disease of to the long standing and slow wasting. It should be our object powers o^t to push the nourishment to the maximum point of tolerance ; individual - but absolutely limited by the amount of assimilative powers of the individual. As soon as we exceed the power of assimi- lation by any quantity of food, we throw an added burden upon the already over-taxed system by forcing it to dispose of the surplus. And since the circulation must be drawn upon in order to dispose of any surplus food, the circulation is diverted in an undue degree to the gastro-intestinal canal, and an anemia is created at the point of infection. Improper feeding will thus interfere, or wholly prevent one of the main assets in the conquest of disease hyperemia. It is not difficult to estimate a patient's assimilative powers. Symptoms like distress in the stomach, fullness, sleepiness and dullness in the head after meals, languidness, all point to over-feeding. The rapid accumulation of fat should not be looked upon without apprehension. Such a gain in weight does not indicate a gain in strength and resistance. On the contrary, a rapid accumulation of fat such as is indicated by a rapid gaining of weight without an increase of strength, points to a process of surplus food disposal which some patients acquire as a protection against stagnation, but which requires an unusual drain on the cir- culatory mechanism. Hence a circulatory insufficiency at the infected area is followed by the retrogression that is so often noticed in such patients under the least adverse cir- cumstances. Nourishing food and well masticated, in quan- tities easily assimilated, and proper bowel action, are the essentials of proper dietetics for the tuberculous individual. The following three radiographs of pulmonary conditions will be found interesting in connection with diseases of mixed* infections. They represent three distinct types of tubercular pulmonary disease modified by mixed infection. 202 TUBERCULIN AND VACCINE The first, Fig. 46, represents a mild tubercular condition lasting over a period of two years with very little pulmonary destruction. A hemorrhage was the first sign of the disease followed by a persistent but mild cough. Bacilli did not appear in the sputum So few were the physical signs in the lungs that my diagnosis of pulmonary tuberculosis made at the time of the hemorrhage was severely criticized and denied by five physicians under whose treatment the patient came during the two years. At the beginning of the third year, the cough began to increase and became productive for the first time. The amount of expectoration steadily in- creased in quantity and became more and more purulent in consistency. Abundant tubercle bacilli were now demon- strated in the sputum, a circumstance which brought the patient back under my care. The physical signs were those that point to the condition as shown in the X-ray photo- graph. Fig. 46. Although both apices were the seats of considerable cavities, the rest of the lungs is clear. The mild apical lesion became the seat of mixed infection with the forma tion of a true abscess in each upper lobe, causing rapid disintegration of the tubercular tissue and remaining the seat of a constant purulent production. Without mixed infection treatment, tuberculin, while it may prevent the spread of the disease beyond this localized area, cannot stop the pus formation in the cavities, nor distressing symptoms which it produces. The second. Fig. 47, represents a more widely distributed tubercular process. The tubercular infection began after a grippe infection; the cough, which was mild, persisted for a year and a half with but slight expectoration. The patient, however, lost rapidly in weight and in strength, night sweats were persistent in short, he presented a typical picture of pulmonary tuberculosis of the slowly progressing type. To- wards the end of the second year of his illness an attack of grippe brought, about alarming symptoms including a severe hemorrhage, and the patient was removed to a high altitude where after three months of treatment and rest in bed, the - MIXED INFECTIONS IN PULMONARY TUBERCULOSIS 203 acute symptoms subsided, but the amount of cough and expectoration increased to such an extent that it interfered with the patient's sleep, and frequently brought on attacks of vomiting. The patient was then sent to Denver, Colo- rado, where he gained in weight and improved in every way except in the amount of cough and expectoration. He re- turned and applied for tuberculin treatment at the New York Polyclinic Hospital. As will be seen in the radiograph, the left lung is the seat of a cavity in the upper lobe near the apex, and al- though there are small foci of healed tuberculosis through- out, the lung is the seat of compensatory emphysema. The fact that there. is a contracting cicatricial form of healing in the left lung with compensatory emphysema in the right, is sufficient evidence that the patient possesses a fair amount of recuperative power. But the mixed infection interferes to the greatest extent with the complete arrest of the process. Under mixed infection treatment and tuberculin adminis- trations, the patient has improved far more rapidly than under special climate and sanitarium treatment. After the first month of immunotherapy the patient returned to work and has never lost a day for the last three and a half years. The third, Fig. 48, illustrates a case of a tubercular infection following upon a fertilized field prepared by a ten-year-old chronic bronchial infection. The amount of hypersusceptibility was never high so that the tubercular process was never acute. The following is a. copy of the X-ray report made when the patient first applied for im- munotherapy in December, 1915. Radiographic examination of your patient, X, shows a marked degree of involvement of practically all of both fields. There are large cavities in the left upper lobe. All the costal cartilages are markedly calcified, and there is little evidence of calcific deposit in the pulmonary fields. Doctor Y. A year later the following radiographic report was made of his condition, which is an interpretation of the third radiograph here illustrated (taken in November, 1916). 204 TUBERCULIN AND VACCINE Radiographic examination of your patient, X, shows a marked degree of clouding and infiltration of both pulmonary fields. The upper third of the left pulmonary field is consolidated. There are bands of adhesions and a portion of a cavity wall in the middle of the left pulmonary field. The right pulmonary field shows a moderate degree of compensatory emphysema. The cardiac shadow is drawn to the left. Doctor Y. In 1913, the patient had a very serious hemorrhage followed by a, long confinement in bed. In 1915, or just prior to the beginning of tuberculin and vaccine treatment, the patient suffered an acute exacerbation of the mixed infection with high temperatures, causing extreme emacia- tion and confinement to bed for two months. It was at the earnest solicitation of the patient's family that I under- took his treatment. They wanted him to have every com- fort and hope for the last months of his life the patient being fully aware of the hopelessness of his condition. His history, together with an examination of his sputum, re- vealed to me the fact that a mixed infection was responsible for the most distressing symptoms cough which was rack- ing and constant especially at night, and expectoration which was purulent and very profuse. The patient ran an after- noon temperature of 100.5 to 101.5. Improvement commenced after two months of treatment with tuberculin and vaccine. After six months of treat- ment, the tubercle bacilla disappeared from the sputum. The cough became less severe during the day and disap- peared entirely during the night. Fig. 48 is a radiograph of the patient's chest at the conclusion of treatment. The patient is greatly improved and at this writing (six months later) is still maintaining his improvement. A comparison between the two reports shows a definite structural improvement as well as a symptomatic improve- ment. I did not publish both radiographs because I did not intend to show structural changes at this point, I merely publish the last radiograph in order to show that even in such an apparently hopeless condition, the combined vaccine and tuberculin therapy can do much to improve a patient. 02 CHAPTEE VI SURGICAL MEASURES To be absolutely correct, this topic should be headed " Tubercular Surgery," for experience has revealed the fact that surgical principles as applied in general surgery do not Surgical principles apply in like manner in tubercular surgical conditions, must be Hardly a day passes without bringing further evidence that ^" '" general sureerv when applied in tubercular conditions does a pp. hcatlon in tubercular more harm than good and sometimes irretrievably injures the conditions. patient. One main reason for the unique situation that tuber- cular processes offer, from the surgical point of view, is the fact that the tubercle bacillus is not a pyogenic organism, and that its infective process is in the main extremely localized. The action of the tubercle bacillus is entirely local, its spread means an involvement of a larger area but still localized. It produces no effect in the blood circulation; and when the tubercle bacillus does get into the circulation it may lodge in glandular structure distant from the point of infection and become localized there. All this occurs very slowly. So slowly, *in fact, that the natural resistance of the body against the tubercle bacillus is able to localize or limit the infection. And it is only after a long standing immune response bringing about a high grade of hypersusceptibility that we may get a general, dis- seminated tuberculosis. That is extremely rare; and when it does occur, we know that it comes more frequently after radical surgery than when surgery, however necessary and conservative, has been altogether withheld. In fact, in tuber- culosis, from the standpoint of surgery, conditions hold true directly opposite to those that apply in other infections. For instance, in other infections surgery will prevent a general septicemia, and will prove effective in proportion to the promptness of its application. In tubercular infections, on the contrary, general infection occurs in direct proportion 200 TUBERCULIN AND VACCINE to the amount of surgery applied. Hence, the entire negl'ect of surgery has rarely produced a general dissemination of the infection. The principal The whole subject of surgery in tuberculosis can there- Iurtfi r fore be limited to its application as a .means to reduce symp- toms and prevent extensive localized destruction. In fact; i. The preven- t ] ie mos t important reason for its application is for cosmetic tion of undue destruction. effects. ficadonf dl Most of the infected areas ,will finally break down and drain by means of fistulas. However, there is a great deal of pain until that occurs, hence, the application of surgery for the purpose of forestalling extensive destruction add for the amelioration of pain. On the other hand, we must not overlook the importance of proper surgery in tubercular conditions for cosmetic effects. .Breaking down of tubercular processes produces ugly scars, and by getting ahead of such breaking down with the proper surgical interference, we may prevent the forma- tion of scars, or we may at least reduce them to a minimum. Nature's The extensive operations that have been recently devised icaHze ail ^ or restoration of function, for the limitation of progres- tubercuiar >nndm the following four distinct forms: surgical The first is the pure tubercular process which in healing C p S u u r r e es ' becomes absorbed, disappearing entirely for the most part, tubercular n-,, 1-1 c T infiltration, Ine second is the process of cicatrization. A tubercular leaving no area may be filled in with connective tissue forming; a hard gross alteratlon on healing; cicatrix. This may or may not become impregnated with 2. Fibrosis, calcium salts. Depending upon the extent of the original behind Tmass process, it mav on healing, leave behind an area of altered thesi2C f " . which is in structure which if near the surface, forms a palpable mass, proportion to The third is a tubercular process modified by mixed the ordinal* infection, which brings about a slow suppuration with pus process; . 3. Tubercular formation. inflammation The fourth is a process of liquefaction within a protec- m 1 ['" [ dby tive capsule surrounding the original tubercular area. This infection; liquefaction might remain unchanged for a long period. It tionpius is known as " cold abscess." However, the cold abscess may ll( i uefactlon ' <* or cold become infected and change to the suppurating variety by abscess breaking through to the surface. Again, it may terminate by the secretion from the cells lining the wall of a tryptic ferment, which, acting as a digestant upon the capsule wall? and finally on the tissues beyond, breaks upon the surface and expels its contents. This process of " pointing " of a cold abscess through the digestion of tissue must be distinguished from the " pointing " of inflammatory abscesses through suppuration. The former process is sterile, therefore much slower; and when the surface is approached, there is a direct sloughing of tissue instead of mere breaking open as in the case of ordinary abscesses. CHAPTER VII THE SURGICAL TREATMENT OF TUBERCULAR GLANDS Classification: The classification of glands with relation to their surg- '' Q lnf,! a ^?na ical treatment differs from the classification with regard to 2. oUppuraiing glands. the tuberculin treatment. Whereas the one classification glands. bears upon the relation of glands to the constitutional mani- festation of the disease, in the present classification we must consider the nature of the local process in relation to local treatment. Thus we distinguish three varieties: the soft glands, the suppurating, and the cicatrized. Soft Glands soft glands S ft glands are cold abscesses. The gland capsule re- are the same .. i .1 i i i T n i i in structure mains intact while the parenchyma becomes liquefied dur- ing the tubercular process. This liquid is mucoid in char- abscesses. acter and is interspersed with particles of caseous material. The older this cold abscess, the less of this caseous material floats in the fluid, for the caseous material precipitates to- wards the wall of the abscess and organizes into a false mem- brane of varying thickness depending upon the amount of the caseous material originally present. This liquid is free from mixed infection and rarely contains the tubercle bacil- lus. It practically forms a healed tubercular area, although the individual may not be free from tuberculosis. Any active tubercular process in the same individual will appear in neighboring glands or elsewhere, but the cold abscess- represents a healed process. Treatment Xhe onlv treatment necessary for this form of glands is- consists of puncture or puncture or aspiration. With a drop or two of one-fourth of one per cent, of cocaine, or one-half of one per cent, of novocaine, injected with a fine hypodermic needle intracutaneously over the part SURGICAL TREATMENT OF TUBERCULAR GLANDS 209 of the gland nearest the surface, the incision^ may be ren- dered painless. The incision consists of nothing more than a puncture by means of a sharp pointed scalpel, the blade being no more than an eighth of an inch wide. If the liquid does not escape through this incision, a circumstance ex- tremely rare, the incision may be widened, or a little sterile normal saline solution injected by means of a sterile dropper will render the contents of the gland sufficiently fluid to escape. A little sterile olive oil should then be injected to prevent contact between the opposite walls of the capsule and a small cotton collodium dressing applied. FIG. 49 If aspiration is resorted to, a fairly large-sized needle should be used, the contents aspirated, and before with- drawing the needle, a few drops of sterile olive oil shoulfl be injected into the sack. Frequently the needle tract will remain open, causing a narrow fistula, and creating the same condition as pro- duced by puncture. This should not be considered detri- mental. On the contrary, the sack may be re-emptied of any re-accumulation, by the use of the eye-end of a needle or even with a toothpick dipped in iodine, pushed into this fistulous tract. With an ordinary eye dropper a few drops of sterile olive oil should be injected after each time the sack is emptied, in order to prevent the rubbing of the sur- face of the sack, thus preventing re-accumulation of secretions. Every step of this treatment must be carried out under strict asepsis strict asepsis. By the use of iodine on the skin, the aspi- rating needle will carry no infection within ; and by the use of a little collodium dressing or alcohol compress over the 14 210 TUBERCULIN AND VACCINE puncture, subsequent infection of the cold abscess will 'be avoided. , Both puncture and aspiration are carried out mainly to get ahead of the process of trjptic digestion which is bound to set in when a cold abscess existed for any length of time. Ugly scarring has resulted from the sloughing of the skin over cold abscesses through the process of tryptic digestion. Aspiration If we succeed in getting ahead of the tryptic ferment Seated formation, the re-accumulation of secretions will become until no ] ogg ant | j eg until the sack becomes contracted upon its reaccumulation takes place. more solid contents, that is, the caseous false membrane which now forms the only contents of the contracted capsule. The contents may be slowly forced out by the further con- traction of the capsule and complete healing take place; or it may form a nodule forced out upon the surface of the skin which heals beneath. The nodule dries and eventually falls off just as a scab does, leaving a whitish scar beneath. Suppurating Glands suppurating Suppurating glands are tubercular glands which have glands are local pyogenic become infected with a pyogenic organism, usually the prolong^ by staphylococcus. Here we have a tubercular process ren- the tubercular dered active by mixed infection, and an ordinary abscess process. . * 7 formation continued by the tubercular process. Occasionally the removal of the mixed infection will be sufficient to cause the healing of the tubercular process with- out any other treatment. However, in most cases a course of tuberculin will do away with the tubercular process and will suffice to bring about a healing by removing the very clement that prevents the natural termination of a staphy- lococcus abscess. It is advisable to resort to the latter means of treatment first as the former does not do away with the tubercular hypersusceptibility, and a local recurrence or a new tubercular infection elsewhere may take place. In the treatment of suppurating tubercular glands, the SURGICAL TREATMENT OF TUBERCULAR GLANDS 211 tuberculin inoculation may suffice. We need not bother Special ' f i i p 1-1 treatment about a vaccine lor the mixed infection until it becomes evi- is not often dent that the mixed infection is deep-seated and requires neces! special treatment for its elimination. If during the treatment with tuberculin the first dilu- tion has been reached without having produced any effect upon the local process, a vaccine treatment for the mixed infection should be undertaken. Cicatrized Glands Cicatrized glands are glands enlarged by the tubercular cicatrized process and healed by the formation of scar tissue. In other glands that words, healing has taken place by fibrous tissue degeneration. g"osls This process of healing of tubercular glands unneces- sarily forms a discouraging feature in tuberculin treatment. To the patient the palpable gland means the persistence of the disease and occasionally even the physician may not realize that fibrous healing jmay take place in glandular tuberculosis as in lung tuberculosis, and that fibrous -healing in glands may leave them palpable or even as large as they were during the height of the infection. I therefore call particular attention to this form of heal- special , i i -. treatment is ing oi the tubercular process; so that we may not under- almost always rate the tuberculin treatment when this form of healing necessar y- occur? in a case of tubercular glands. For here, just as in bone and joint tuberculosis, we cannot expect tuberculin to eliminate the results of fthe tubercular infection while it eradicates the infection itself. . After the disease has been converted into a purely local process by means of immunotherapy, the following methods of treating the local condition may be resorted to: First, we may inject substances within the glandular stroma in order to soften the fibrous tissue, by producing a destructive or cauterizing process. Second, we may remove what remains of the glands through surgical interference. 212 TUBERCULIN AND VACCLNE softening of Sof tening of the hard cicatrized glands may be brought mass^y 1 " about by the injecting of iodine or synthetic guaiacol into means of ^ cen te r o f the gland ; or even a drop or two of carbolic chemicals. . ' . may be injected through a hypodermic needle, using alcohol on the surface of the skin to prevent burning. After two or three injections, about a week or two apart, the gland will begin to soften and may be treated as a soft gland. The following formula will be found useful for this purpose: I Synthetic guaiacol Merck, gm. 6 Metallic iodin, " 3 Sodium iodid, " 6 Glycerin, " 30 Saccharin, " 0.50 Distilled water, " 10 Misce et solve. Conservative When resorting to surgical measures in the treatment of cicatrized glands, radicalism is unnecessary. Tuberculin has eliminated radical surgery in tubercular processes, par- ticularly in tubercular glands; and once hypersusceptibility has been removed, new tubercular processes need not be feared. Under local anesthesia and through the smallest possible incision, the gland can be easily separated from its surrounding tissue by blunt dissection or scissors. The inci- sion may be closed by subcuticular suture. Where there are several enlarged glands, it is best to make a separate incision for each, instead of using one large incision for the removal of all the glands. A large gland may be removed by morselation through a small incision. CHAPTER VIII BONE CAVITIES, SIN-USES AND FISTULAS Infection of bone is synonymous with chronicity. The Bone infection nature of bone tissue precludes hyperemia from the point with"hoTicity of infection; hence, the insufficient immune response during the infection, and the retarding of anabolism through insuf- ficient blood supply during healing. Again, while in the case of soft tissue the destroyed tissues escape in the form of pus, in the lease of bone, the products of infection remain solid, forming sequestra which make the escape of destroyed tissue difficult or impossible. We are here dealing with a foreign body, which in addition to the infection contributes materially to the chronicity of the process. Even without the formation of sequestra, the healing of The formation bone tissue and the formation of new bone is so slow that and s i nuses . wound discharge takes place for a considerably longer time than in soft tissue. The route through which these products of infection are discharged must remain open for long periods of time. Assuming a similar function to that which natural canals possess for the discharge of excretion, these passages become lined with a granulation tissue layer, which is protective by preventing the closure of these channels. The result is the formation of 'fistulas and sinuses. The treatment of tubercular bone and joint disease must A combined embrace besides the eradication of the tubercular infection, essential, which was discussed in Part II, the elimination of mixed infection and the restoration to as nearly normal a condition as possible the structural changes that have taken place as a result of the tubercular infection. Mixed Infection Mixed infection in cases of tubercular bone disease dif- fers in but few respects from mixed infection in other tuber- 214 TUBERCULIN AND VACCINE The utilization C ular infectious. The difference can best be understood if of the immune _ _ .. ... ,, , response is we bear in mind that we have to deal with an inferior blood ^udToT 1 b supply when the immune response is utilized in treatment of hyperemia. fane infections. Once we have this fact established, we are ready to employ infinite patience in the treatment of bone disease. What is more, there is nothing to impede our progress once we start, for this class of patients will permit all the time and experimentation that a course of treatment re- quires. All they wish in return is a reasonable hope for an eventual cure. For of all tubercular cases these are the most pitiable. Although their lives are not threatened, and although in most other respects they are physically well, still their condition stands between them and self-support, often between them and self-respect. For the tender care and sympathy extended to the sick spends itself in time, leaving these patients to the monotonous routine of daily dressing their wounds and obtaining their livelihood as best they can. In any case they are a burden to their families, and often to the community. This is the hopeless condition in which these sufferers approach us. So that it is no won- der that any hope of cure will be welcomed, no matter how much time or experimentation it involves. That is why the element of time does not have to be seriously considered in a course of treatment such as bone tuberculosis requires. Treatment. After the tuberculin treatment has been applied for a week or two, it is advisable to begin the treat- ment for the mixed infection, proceeding as follows: A smear of the pus is made, and stained with methylene blue for the diagnosis of the organism causing the mixed infec- tion. If no bacteria are found, a further test as to the sterility of the discharge should be made by inoculating a culture tube of serum agar. If no growth appears in forty- eight hours, the pus discharge is due to the tubercular pro- cess alone, and no further attempt to influence the local condition by means of vaccine need be made. The tuber- BONE CAVITIES, SINUSES AND FISTULAS 215 culin treatment for the systemic condition, and bismuth paste for the local condition will suffice. If, however, the smear or the culture tube, or both, revealed the presence of mixed infection, we proceed to treat the patient with a stock vaccine after a diagnosis of the causative organisms is made. (See Chapter IV.) The mixed infections occurring in tuberculosis of bones Mixed and joints are the simplest forms of infections for vaccine in bone and treatment. The causative organisms in the largest majority ' omt dlsease of cases are the staphylococcus, albus or aureus. The strep- simplest forms. tococcus comes next in order of frequency, occasionally the pneumococcus makes its appearance, and very rarely the colon. Thus it will be seen that the most easily distinguished bacteria, both in smear and culture, the staphylococcus and the streptococcus are responsible for most cases of mixed infection, in bone and joint tuberculosis. A stock vaccine of one of the organisms found in the pus Stock va ccines should be tried for a few weeks, the dosage being the same ma y be 7 employed. as for chronic mixed infections (Chapter IV). And if no Autogenous effect is produced such as a change in consistency or in the gh quantity of the discharge, a stock vaccine of one of the other resorted to ~ ' . when stock organisms should be tried for as long a time as the first It vaccine has may be necessary at times to obtain an autogenous vaccine to produce the desired effect. Especially is this true in the case of the streptococcus, where the strains are so numerous that the strain causing the infection may have been over- looked in the manufacture of the polyvalent stock vaccine. As I have previously stated, it is better to use a vaccine vaccines of one organism at a time in case of multiple infection, than ^"^^"j to use vaccines for all of the organisms at the same time. Xot that there is any serious objection to the latter method, but since the tuberculin treatment must necessarily last a length of time which offers ample opportunity for the former or slower method of vaccine treatment, it should be adopted as it has distinct advantages. Thus it will often be found that when using a vaccine against one of the bac- 216 TUBERCULIN AND VACCINE teria in a multiple infection, the other bacteria will dis- appear spontaneously, making it at once evident that they were simply parasitic forms and took no part in the mixed infection. On the other hand, it may happen that after the use of a vaccine against one of the organisms, another may so increase in number as shown in a subsequent stained smear, that it leaves little doubt as to its participation in the infec- tion. A vaccine for this organism should be at once em- ployed. All these variations will become evident only if the vaccine therapy is applied ini a spirit of scientific inter- est the empirical use of vaccines will not only fail in a great many cases, but even when successful, will add noth- ing to the physician's experience which can be utilized in subsequent cases. CHAPTER IX BISMUTH PASTE Having considered the treatment of the etiological infec- Bismuth tion and the treatment of the mixed infection of tubercular prominent cavities and sinuses, we must now turn our attention to the element m the reconstruction of tissues in order to remove the mechanism, TREATMENT. which though it was established as part of the defensive pro- cesses of the individual, was so well established that the body cannot rid itself of it spontaneously once the reason for its existence has passed. A better understanding of the mode of action of bismuth Formation of paste will be obtained if we have clearly before us the channels, mechanism by which pathological cavities and sinuses form and continue their existence. In the first place nature builds a wall around a chronic infection as part of its pro- tective mechanism. The products of the chronic infection must escape hence the formation of sinuses and fistulas. Once the process is chronic, the necessity for the existence of the fistulous tracts will remain for a considerable length of time. Mature, therefore, lines these tracts in the same manner as she lines natural passages with a secreting mem- brane. ^Yhat was originally meant as protective construc- tion, thus becomes the means of the prolongation of the pathological process. These cavities and sinuses are con- stantly filled with a sero-purulent irritating accumulation, aiding materially in prolonging their existence. The sero- purulent accumulation is brought about by the negative osmotic pressure, causing a flow of lymph and serum toward the empty space forming the cavity. This offers an admir- able situation for mixed infections. The serous accumula- tion forms the best cultural media for bacterial growth the proper temperature is always present, and the bacteria are at the same time beyond the reach of the antibodies. 218 TUBERCULIN AXD VACCINE Action of When such a cavity is filled with bismuth paste the fol- bismuth paste. , lowing results are produced: First, the bismuth paste possessing a specific gravity far in excess of the surrounding tissues, practically stops the irritating accumulations. Second, mechanical pressure exerted 'by the bismuth paste upon the lining cells causes atrophy of these cells thus removing one of the principal causes that prevent healing. Third, bismuth acting as a foreign ,body stimulates the contraction of the tissues upon it so that the cavities hold less and less bismuth with each subsequent injection until final obliteration of the cavity takes place. Fourth, according to Beck, bismuth possesses a kymo- techtic property aiding in the production of hyperemia the element that is most needed in overcoming chronic disease. Fifth, bismuth paste possesses the quality of retaining to some degree radio-active properties, which are imparted to it by the X-rays. Frequent Roentgenographic examina- tions while the tubercular tract is filled with bismuth paste will facilitate the cure of these conditions. Composition of Bismuth Paste Bismuth paste consists of bismuth and vaseline. Hard paraffin and white wax is added when, owing to a large fis- tulous opening, it is difficult to retain, and a more solid con- sistency is required. The usual proportions are one-third bismuth, two-thirds vaseline. "When five, ten or fifteen per cent, hard paraffin, together with five per cent, white wax are added, the bismuth content may be reduced to thirty per cent., and the vaseline quantum sufficit. The bismuth may be further reduced to twenty, ten or even five per cent., when the injection is made into a great depth, and where its removal may prove difficult, also where the cavity is of such size that the total quantity of bismuth paste injected BISMUTH PASTE 219 is large. I have seen lanolin used instead of vaseline. That is distinctly contraindicated, as lanolin is an absorbable base and would encourage the absorption of bismuth along with it. The use of lanolin as a base is probably responsible for the fear that bismuth paste may cause bismuth poisoning. In ten years of experience with bismuth paste, I have seen but one case where there seemed to be a tendency to bismuth poisoning, and that occurred in the case of pulmonary abscess, where fourteen fluid ounces of the paste had been injected in a patient for diagnostic X-ray examination. It was afterward discovered that this patient possessed a spe- cial idiosyncrasy for bismuth the poisonous symptoms ap- pearing after the injection of a very small quantity. Aside from this case, there never occurred the slightest suggestion of bismuth poisoning in the hundreds of cases that have come under my personal experience. Bismuth Paste Formulas variations T IT TTT TV inthe bismuth paste Bismuth Subnitrate 33 1-3 10 20 30 formula. Paraffin (120 melting point) .... 5 White Wax 5 Vaseline. . 66 2-3 90 80 60 100 100 100 100 With regard to the therapeutic application of bismuth paste, the following are the most important points requiring attention : The bismuth paste must be absolutely smooth, as solid careand particles of bismuth may become separated from the vaseline fo'hlJecti and form a concretion. Only such quantity of the paste should be sterilized as is required for immediate use, for the frequent heating of the bismuth paste spoils the con- sistency of the vaseline and allows the precipitation of the bismuth. The sterilization of the bismuth paste for imme- diate use is accomplished: (1) by boiling a receptacle large 220 TUBERCULIN AND VACCINE enough to contain the quantity of bismuth paste required, together with the syringe; (2) jby putting the required amount of bismuth paste in the sterile receptacle which is then placed in boiling water. The flame under the boiling water is turned out, ,and the bismuth allowed to stand in the hot water for ten minutes. This permits of a pasteurization of the bismuth paste, the cooling of the water during the ten minutes not going below the pasteurization point It is not necessary to boil bismuth paste to obtain sterility, as both bismuth and vaseline inhibit the growth of bacteria, hence pasteurization is sufficient to kill any bacteria that get in during the manufacture of bismuth paste. The more fluid the paste, while being injected, the more certain it is to completely fill all the sinuses and cavities. However, care must be taken not to allow the paste to be hot enough to cause pain to the patient. Bismuth Injections The proper syringe is a plain glass syringe with an asbes- tos packing, the syringe varying in size from two drams to four ounces. It is best to have the tip blunt and rounded, as per illustration (Fig. 55), rather than a catheter end which would go into the fistula. I prefer to avoid putting into a fistulous' tract any hard instrument which might cause injury and bleeding. The blunt point placed against the fistula's opening with gentle pressure will answer the pur- pose every time. Inject the bismuth slowly, using steady but gentle pressure until the patient feels discomfort from distension, or until the resistance causes an overflow of the paste around the tip of the. syringe, or until the bismuth shows through the other fistula or fistulas. If more than two fistulas exist a gentle pressure is applied on the mouth of the fistula where the bismuth first makes its appearance, and the injection of the bismuth is continued until it begins to show at the mouth of the next fistula. The same pressure should be applied to the third fistulous open- BISMUTH PASTE 221 ing if a fourth exists. This procedure is continued until the bismuth appears from all the fistulous openings. Only then are we certain that if a cavity exists, it is filled with bismuth, and that all the accumulations in that cavity have been removed ahead of the advancing bismuth column. If fistulas exist which do not communicate, bismuth should be injected into each separately. Bismuth Paste Retention. Although bismuth paste is varying of value in removing the infective and irritative accumula- C Q b tions from fistulas and cavities, it cannot prevent reaccumu- paste for T . . . . , . retention. lations nor stimulate contraction 01 the cavities unless it remains there for at least twenty-four hours, preferably forty-eight hours at a time. It is, therefore, necessary to prevent the immediate outflow of the bismuth paste after injection. That can be done in the first place by varying the consistency of the bismuth paste according to the size of tie fistulous opening. For instance, a large opening must have thicker bismuth paste, whereas for a very small one a more fluid bismuth paste can be employed. In the second place, the consistency of the bismuth paste should depend upon the depth and the distance of the cavity from the surface. A cavity will retain bismuth paste of a lighter consistency for a sufficient length of time if the outlet to the surface is formed by a tortuous and long fistulous tract. Whereas a channel that is near the surface and has a short outlet will have to be filled with a bismuth paste that remains quite 'hard at body temperature. The consistency of the bismuth paste can be varied by the addition of five or ten per cent. hard paraffin (see formulas, page 219). The fistulas can be sealed with cotton collodium or plugs of cotton or gauze, retained by adhesive plaster. Small tampons may be used, pushed into the channel and prevented from falling beyond reach by an attached string which is tied over an adhesive strip going across the opening; or a string attached to a piece of adhesive plaster may be placed at opposite sides of the fistula and at some distance from it. 222 TUBEKCULIX AND \ 7 ACCIXE By tying these strings together, the adhesive plasters are drawn together, pulling the skin with them, thus closing the fistula. intervals Frequency of Treatment. : The best interval between inactions, and injections is forty-eight hours. If the bismuth is well re- instruction to tamed, the intervals may be longer. However, the interval patients as to i i -r i the care of should not be longer than a week. It is best to renew the during""/ 8 bismuth paste in the (diseased area at least once a week for intervals. t wo reasons : (1) to prevent the formation of concretions; (2) to avoid unfavorable results that may occur in a fistu- lous branch which may not have been filled by the bismuth, and which retains its irritating and infective contents as a result of the blocking of the exit by the bismuth. In case redressing of the fistulous opening by the patient becomes necessary during the interval, the patient is instructed al- ways to use gauze or cotton saturated in alcohol, to avoid the constant danger of reinfection. Where there is only one fistulous opening, making it therefore impossible to remove the old bismuth ahead of the advancing column of the fresh bismuth, and where the bis- muth does not spontaneously ooze out during the interval, we follow the advice of Beck by using injections of sterile olive oil to soften and wash out the bismuth just previous to the injection of the fresh paste. The Proper Direction of Bismuth Paste A closer study of a number of cases of open bone disease that resisted the combined treatment, has yielded a more intimate understanding- of the mechanism which continues present to allow of the the existence of cavities, sinuses and fistulas. Aside from the escape of the -11 -i ,. , - ,, , - purulent weli known purpose lor the existence of fistulas and sinuses drainage, the study revealed the importance of a proper direction for such drainage in relation to bismuth paste injection. This finding at once explained that the former resistance to treatment in many cases was due to a faulty direction of the flow of the bismuth paste. No sooner was BISMUTH PASTE 223 this direction altered in such a way as to conform, with the principles of bismuth paste injections, than conditions which resisted treatment for a number of years promptly began to improve and soon healed. In the process of formation of fistulous tracts the area through which the inflammatory products have to traverse in order to reach the surface may be composed of such tis- sues that in taking the direction of least resistance, the course becomes zigzag and tortuous. For instance, when heavy fascial layers interpose between the point of bone infection and the surface of the body, the direction of drainage may be deflected by this fascia for a varying distance, allowing it to come to the surface where the fascial layer either thins or disappears. The fistulous opening, therefore, will appear at a point removed from the point of bone infection in fact, at times the distance is so great that only special investiga- tion will discover the relation between that fistulous opening and a given bone infection. In other cases the suppurative process takes two or more directions before reaching the surface. But not all such fistu- lous tracts need reach the surface. For, as soon as one or two of the tracts do reach the surface, the pressure is relieved and the process in the rest of the sinuses discontinues. The result is the formation of blind fistulas or pouches. It is difficult to fill completely blind fistulas and pouches counter which are really, cavities, having only one opening at some ^ p u e s n t '"f t s en be distance from the cavity itself. Where several counter opeti- established ! i . i i i i . . - surgically. mgs exist through which the bismuth can escape, it is almost impossible to fill such blind fistulous pouches. The advanc- ing bismuth column turn? the corner and leaves through a neighboring sinus, and thus not only fails to completely fill, but even bottles up the discharge in the blind fistula or pouch. This circumstance is responsible for the sudden pointing of a new abscess and the formation of an added fistula during treatment. For the moment such an occur- rence is discouraging and is looked upon as evidence of fail- 224 TUBERCULIN AND VACCINE nre, a ml frequently leads to the discontinuance of the treat- ment. In truth nature has accomplished something which the physician should have done long before established the proper direction for the passage of the bismuth paste. A reference to the diagram (Fig. 50) will render this subject clearer. Roentgenography < without the The direction of the bismuth paste cannot be deter- mined without one or two X-ray examinations made dur- X-ray photo- > graph the ing treatment, and so some mention of the utility of Roent- counter- gcnography in this connection should be made. It is almost impossible to gain any knowledge of the various discovered. channels or cavities whether as to size or direction with- out an X-ray photograph of the entire part involved com- pletely filled with bismuth paste. Probing is to be con- demned even if it were to enable the determination of any- thing of diagnostic value. A glance at Fig. 51 will show how hopeless the probing would be in such a network of channels. The stereo The stereoscopic radiograph is the latest development of X-ray study. By taking two exposures of the same part on separate plates, each exposure from a different angle and the difference gauged to correspond to the difference in the angles between the human eyes, a stereopticon picture is produced which when viewed through a stereoscope shows the part in three dimensions. The exact relations of the various tubercular channels and cavities to the tissues are seen, which render the application of the various surgical meas- ures far more easy. If possible, a stereo-radiograph should be insisted on. Therapeutic The X-ray has another important application in relation applications. to bismuth paste that is a therapeutic application. It was noticed that those cases that were exposed to the X-rays after bismuth injection for diagnostic purposes healed more rapidly than those cases that were treated with bismuth paste but never had an X-ray photograph taken. This led %>-> In v l:lfMl i EXPLANATION OF FIG. 50 When bismuth paste is injected at F2 it will go in the direction of least resistance and escape at Fl. If Fl be closed by a dressing sufficient to prevent the escape of the bismuth, the paste will then rise until it reaches b, where the branch sinus d is given off. Then instead of rising to fill the blind sinus a, and the cavity c, it takes the direction down through d because that is the direction of least resistance com- municating as d does with the surface through the fistulous openings F3, F4, F5, F6, F7, and F8. Whereas, in attempting to fill a and c, the paste would have to replace an amount of discharge which has no outlet once the point b is filled. In this case, a puncture incision, after a little cocaine infiltration, at X which was nearest the surface, removed the only barrier to a cure. Subsequent bismuth injections were given through this puncture at X, which permitted of an easy filling, of the entire system of fistulas and cavities. V '' V 4ibtl something : Irefore the bi.srauth will rend- . abject 1 ntgenography Witt aido > X-ray examination-: inr- grapi u>.n ;,hould be made. It coun open oa .oil 10 KpiTAKAj'ijcS ( >f the various cann discc lf> aoiJemib add ni o^ Iliv/ di 8*1 dt IsJo9(;iri i stajsq rfiumeW' jfMi'-u'fhjs jjfiiae;>-ib a '{d Leeolo 9I H Jpl.ta Ji liJarj t.?:iT norli Iliv/ nteM[ srft ,rf Ji/msid . ^ift In 9qBoe9 t srfi 5o I)9igni norfT .Tto navi^ si b sirnis 'rfonnid arf^ siotfw t d ' aojiv/rib sift *9iij>J di ,o vtivfia srft fms t B erraie Lnifd ,otft lift oi - -/!;, i:) ;>'Mi/ii*ia9i jsr^I lo noriaoTth orfi $i iaifi saw/sosirJ b JyJoiifi wob ^miirwqo suoludaft aifj ilgi/oirfi oojsfaue e>rfd iWiw 9ob b 8jB saiJBoini/m ,-> hnu js lift ol TjfiiiqriioJJft ni ,3J50i9d7/ .S"? bna .tT ,01 ,3^^ ,81 C'ti M.if rfoiiiw og'iiidoaib lo dnuomr. no 9D[q9T oJ syxjif blwow 9ieBq 9rii The T)tlB ,noi.bni 9'iuJofir/q s ,S3a sirij ni .boHft si d dnioq 9fW aono dsliuo x-ra fiovomaj ( 9-jj;lii/-? 3ffd JgsiKsn e.Gvr ri-ji/Iw X ds .noideidlSai aniBOOO sIWH c novrs 9 - iov/ snoijoo[tii if It/maid dnaupggduS .91110 oJ igin^d ^Ino 9di oifj 1o aniffft ^BO an lo b9itiirn9q dohfw ,X djs gTWioniirj girfj bB ] ti con picture is -rt='' p.-rpr^^ healed more ; ;.d- n**-}-* < .".-- > i-d ^Ith bi?rrmth Thi* Ir-d FIG. 50 FIG. 51 FIG. 51 is a radiograph of the same condition illustrated by the schematic drawing, Fig. 50. This young man, twenty-two years of age, had tubercular hip joint disease which during a period of five years totally destroyed the hip joint. The network of channels had eight fistulous openings which, in spite of all the modern methods of treatment, continued to discharge through the five years, and required from two to four dressings a day. A course of tuberculin and vaccine treatment for the mixed infection and bismuth paste injections pro- duced a gain in weight ,and strength, and reduced the discharge so that only one dressing a day was required. But beyond this improve- ment, the condition resisted treatment for many months until this radiograph was made immediately after the careful injection of bis- muth with all the fistulas sealed except one at 6, and an amount in- jected until the patient felt distressed. ( ( See Fig. 52 of the same patient taken four months later.) 15 .r arfi ^d bsiirrtaudi noiiiLuoa gm^e ariJ io dqfiigoifuri B ai 13 .oil lo siB9- owi-^JrrewJ ,niifn gnuo^ aiifT .05 .yi'i ,fiiv/Bib 9iJj;raoiI-j3 ovit lo boiioq ii gnin/b rfoirfv/ 3?.B3ib inioi qhi lulii'jiadut f)j:i( ,9^1; i:j| alsHnnrfa Jo jliov/ion srfT .daioL qii( orft bs^oiJaeb y[[r,t-j lo Lid io f-ooBiT .steaq diomeid lo feqoib wal c feiJirrifj/; d-jidv. jd> no Imp, jnioj; qid sdi hn0oiB eai/BsiJ sdJ ni nsss sd UiJa /un: .woled 39! 9fli lo ofnri miai -1U09T on Imfi oLfim RW dq/5igoil)-i gidi soiria i/;9v; ji yl'icofi ?.r if .ni,Hoqqirfc-l[9e IMIJ; Lav'ilqms v/on tii JnsiJcq edT .ooiifq iro;h V. FIG. 52. DIRECTION OF BISMUTH PASTE. FIG. 53 FIG. 53 shows a radiograph of a tubercular hip joint with only one discharging sinus at a. In spite of a course of tuberculin and vaccine treatment the sinus failed to heal and the child suffered recur- rent attacks of temperature ranging between 103 and 105 F. lasting from one to two weeks. A stereoradiograph taken immediately after bismuth was injected under pressure irevealed the fact that the channel opens into a cavity directly above the fistulous opening. This cavity communicates with a smaller cavity behind the ileum, which in turn communicates with a third cavity by means of a channel running through the joint. The third cavity filled with bismuth was easily felt as a mass on the buttock. Under a local anesthesia a small inci- sion was made on the buttock directly over the third cavity as indi- cated by 6. Almost immediately after this procedure the local con- dition improved rapidly and soon healed. No temperature has occurred since. 83 .oil "{Ino rfliw .Jflioi; qirf islimaduj a io dqBigoibuT B eworia 5 .oil brtB nilrmodui Jo sainoa B lo aliqa nl. .n JB aimia gnigiBrfoeib sno -TU09T ho'isltoa blirlo sift bns Ifisd od bsliel eunia edJ /i f,OI bns 80f nesv/Jed gni^nBi siuiBisqai^ \o [siBibammi n9>lBJ /fqcigoibfiiosiaJa A .ejfeew owi oi sno oifi inrft iol 9ffi Iwlfievst oit/aesiq igbno b6Jo9yii BBW rfJurneid stiJT .T>niif9qo auofuigft srfj evods ^Woaiib ^JivBO B oJni enaqo mo} ni riohf-w t mu9li arfi bnirfsd ^iivBO i9llBni8 rfiiw gajfioimjmraoo ^>(iinrrm fgnnnrfo B lo en9fn *^d ^iyjso btiitt a riJiw esiBoini/ramoo ^fiace KR-II ittumsid dim bellit ^iivBO Inirfi ariT .inio'i srfi riguoirfi -ioni Hfima n Bi9rfJ&9nB IBOO! B labnU .jlotxiiod srfi no agBin EB ibl -ibni SK viivBa biiri* 9rfd i9vo ^lioa'iib >IooWud arf^ no sbBrre BBW noia -noa IBOO! 9ffJ^ giubgooiq ehlj loils ^Isifiibsmmi JgomfA .6 x^ b9iaa bennooo acil g-mi/noqmg} ol/L ,fj9ffi9({ nooa ban ^IbiqBi bsvoiqrai noiJib FIG. 53. DIRECTION OF BISMUTH PASTE. FIG. 54. DIRECTION OF BISMUTH PASTE. FIG. 54 is a photograph of the same hip as radiograph, Fig. 53, with a schematic outline of the tuberculous tract, the solid area show- ing the anterior and the ruled area the posterior part of the tract. The heavy dot represents the fistulous opening artificially made. FIG. 55 A young man twenty-two years old, with a negative family history, had nothing in his past history that had any bearing on his present complaint, except that he had had measles and scarlet fever. His present complaint began five years ago with the formation of an ischiorectal abscess which refused to heal and "was operated upon for fistula-iuano. The fistula, however, recurred and persisted for several years. A second extensive operation with no better results waa per- formed a year before he came to me for treatment. The usual routine as to tuberculin, vaccine, and bismuth paste was carried out. But in spite of increased weight and strength, and in ispite of the fact that he was able to return to full duty at his occupation (which he had not been able to do for years), the local condition did not completely heal. There was only one large fistulous opening into which about three drams of bismuth 'paste could be injected, but the fistula was still there at the conclusion of the tuberculin treatment. After careful radiographic study one fistula was found to lead to the sacrum. A puncture incision was made at that point and the bismuth paste in- jected at the new opening until it appeared at the old opening as shown in this photograph. In less than two weeks the discharge stopped. The local condition improved more in the next two weeks than it had in the six months of previous treatment. 5S .Oil ,7'ioiairf vjimfil 9vida9n f> rfiiw ilj ,(KIB'J^ tol ob oJ gfdfl a99d irodK rf'jiil/A oJni gnirigqo suoli;;trt 9gial 9no ^Ino BBW 9i9dT ?.r,-ff Bliiien 9(iJ dud t bdtosiai 9d bli/oo gieBq 1 ifJumaid lo emmb ii-j Tjjl/. .Ifi'jfiiifmi niIiJ9i9diJd 9di lo noieulonoo 9ffi / .ifirr-ioiia r n\J o1 bra! od bnnol ejrw BluJ^it 9fro "^bi/t -ui 'jtixsq iWirniriid 9ilj bnB inioq idi da 9bBtn BBY/ noi&ianr Kf: v.ftinoqo bio -xli d bgussqqc .ii Him; gningqo W9n 9rid JB f)y;if;i(-)8ib 9(ld ?vfoow ov/J nxiili eegl ni .rfqr.iToodoriq eidj ni nwoifa r.>l')ov/ OY/J ix9n 9if^ ni 9'rour J>9vo'iqirii noiiibnoo IBOO! srfT .bgqqoia .1ii9mJ(;9it Riroivnq lo erfdnom xia 9rli ni bBd Ji FIG. 55 TUBERCULAR COXITIS DIRECTION OF BISMUTH PASTE. BISMUTH PASTE 225 to periodic exposure of the more refractory cases that were treated with bismuth paste to the therapeutic X-rays. The results thus obtained are sufficient to recommend the occa- sional exposure of the bismuth filled tubercular channels to the X-rays. 15 CHAPTER X COLD ABSCESSES A cold It has become a matter of principle among the profes- pathoiogTwi sion to ignore cold abscesses entirely. Whether this attitude condition which arose f rom f e ar of mixed infection, or from the desire to requires treatment. leave well enough alone, is hard to tell. Perhaps the bad results obtained from wide incisions and drainage has led to the usual reaction from doing too much to the opposite of doing- too little or nothing at all. infection Personally I could never see the harm in emptying a aspiration cold abscess. As a result of the surgical treatment of a cold abscess, the following three possibilities may arise: infec- tion may take place; the abscess may refill; or the abscess may remain empty, the capsule contracting into a small mass of connective tissue. With aseptic technic developed to its present standard, the mixed infection need not form such an impassable bar- rier to the proper treatment of a cold abscess, especially as the methods used in emptying a cold abscess here described, almost entirely eliminate the danger 'of infection. We do not make wide incisions, nor do we use drainage tubes, nor packing such as is done in inflammatory abscesses of equal size. The purpose The refilling of the abscess is of no greater consequence is t S forestaii than the recurrence of effusion in pleurisy. It entails no the tryptic greater danger than the necessity for re-emptying. How- digestion and * r ' inflammation ever, at the present time, we even can to a large measure which irritation , ,1 /?n p ,1 i will produce. prevent the refilling of the abscess. ISTow, " Why get rid of the cold abscess ? " is the ques- tion. The first and foremost reason is that a cold abscess is a pathological entity and will take away the psycho- logical effect of the benefit from tuberculin if it fails to absorb during the healing of the other tubercular lesions. Secondly, these abscesses are usually on the surface of the COLD ABSCESSES 227 body, and may become infected through the pressure of clothing or through outside trauma far more frequently than through the use of an aspirating needle which is always used with strict asepsis. In the third place, the abscess fre- quently breaks down through a tryptic digestion which may make its appearance at any time. This tryptic digestion is the method by which Mature rids herself of foreign matter when there is no pyogenic organism present. This diges- tion usually attacks the entire surface of the skin over the whole abscess and produces a proportional amount of very sluggish ulcerations with eventual irregular scarring. A staphylococcus infection is almost preferable in a cold abscess to this digestive breakdown, because the former will point in but one place and an incision followed by drain- age will localize the infection, which on healing leaves an insignificant scar. In the latter case, the abscess empties by a sloughing process through the tissues, leaving behind the most unsightly scars. Treatment The best treatment for cold abscesses is aspiration. An Treatment ordinary aspirating needle about the size used for obtain- ing spinal fluid is best. A drop of tincture of iodine aspiration and . the injection painted on the skin over the dependent part of the abscess, O f bismuth and a little ethyl chlorid spray for local anesthesia, is all the preparation that is necessary. The needle is pushed into the abscess, care being taken not to push it too sud- denly and thus injure the opposite abscess wall and pro- duce bleeding into the abscess cavity. All the fluid is aspirated and sterile oblive oil injected through the same needle, filling the cavity to the extent of about one quarter of the amount aspirated. Frequently the needle tract will fail to heal and will form a small fistula through which any reaccumulation will slowly ooze until the capsule entirely contracts. Another form of treatment is by puncture. After paint- 228 TUBEBCULIN AND VACCINE in a very j n g the skin with tincture of iodine, a drop of one quarter of large abscess .... anstuious one per cent, of cocaine is injected at the point where the puncture is to be made. The same knife is used as in the by puncture puncture of soft glands (page 209). then the abscess is and then the abscess treated emptied by gentle pressure and refilled (with sterile olive with bismuth , . . . , . ... paste injections, oil. The bismuth paste syringe, or an ordinary medicine dropper may be used for injecting the sterile olive oil. The amount of oil injected should be about one quarter of the amount of matter withdrawn, or a quantity sufficient to keep the opposite walls of the cavity from touching, as any irritation will hasten a reaccumulation of pus in the abscess cavity. When puncture is resorted to instead of aspiration, and when the abscess is not very large, bismuth paste may be injected after emptying. Bismuth often hastens the con- traction of the capsule, and a rapid disappearance of the abscess occurs as a result. The same may occur after aspi- ration. A precipitate which forms in the fluid content of the cold abscess forms a pseudo-lining to the capsule. The capsule remaining after the aspiration of the fluid, with a solid substance within it, promptly contracts, forming a nodule which may protrude from the surface of the skin, The nodule dries and falls off after a few days, leaving a smooth circular scar behind. When the cold abscess is very large, or when it resisted the above treatment, a more radical procedure is resorted to (in fact the most radical we ever need use) consisting of an incision, never more than one-fourth to one-half an inch long, and followed by drainage. As a drain, a few strands of silk or a very narrow strip of rubber tissue is used. In forty-eight hours we have established a fistula and now can treat the cold abscess as we treat bone cavities. Bismuth paste is injected every forty-eight hours, care being taken to remove first any bismuth paste which has not oozed out from the previous injection. Even a thirty per cent, bismuth paste may be used here. COLD ABSCESSES 229 Under no circumstances should a cold abscess be packed Gauze packing with gauze, nor should drainage with rubber tubing or gauze by means of ever be resorted to. The danger of infection is far less J^,,, when the cold abscess is left without drainage altogether. sauze should be avoided. We may reduce the danger of infection still further by means of an alcohol compress applied to the incision after each treatment, and by means of scrupulous care in steriliz- ing the syringe and the bismuth before use. I have had no serious trouble with infections in treating cold abscesses in the manner just described, although I have opened a great many over a period of eight years. i It is far better, however, to leave cold abscesses entirely alone, than to treat them improperly. The following case is an example of the serious hartm that can be done by the application of the usual surgical principles to cold abscesses : The patient, a man twenty-one years of age, with an old Example, tubercular lesion in the dorsal spine, developed a large cold abscess occupying the entire posterior surface of the left thigh. Without any special indication for surgical inter- ference, an operation was decided upon. The patient was taken to a hospital and under ether anesthesia, a two-inch incision was made at the upper end of the abscess, another at the lower end, and a rubber tube pulled through and left protruding from both incisions, in order to insure perfect drainage. The patient had no temperature, and I believe the lesion in his spine was not active. Three days after the operation, the patient developed a temperature of 105.5 F. with a typical streptococcus septicemia. After the infection persisted [for a week or over, the patient's con- dition became alarming, and I was called in to institute vaccine treatment. An immediate removal of the rubber tube and a thorough washing out of the cavity with alcohol, together with the use of a streptococcus vaccine, soon placed the infection under control. In a week, normal tempera- .ture was again restored. I am quite certain that had one or two punctures been made for the escape of the fluid, followed 2:jO TUBERCULIN AND VACCINE by the injection of a bland, oily substance to prevent the rubbing of the opposite walls, the abscess could have been healed without any trouble. I might add here, that, owing to the size of the abscess (it held nearly a pint of fluid), it would have been .against the best interest of the patient to have omitted treatment altogether, although no treatment would have been better than what the patient first received. When the digestive process sets in, the sloughing of the skin over the abscess is so extensive that great discomfort, lasting for months on account of the slow healing ulcerations, is produced. CHAPTER XI EMPYEMA AND LUNG ABSCESS Purulent effusion in the pleural cavity is a complication in tuberculosis that occurs in four different ways : (1) Infection of serous effusion; (2) The pointing and breaking of a pulmonary abscess into the pleural cavity; (3) The ulceratiou of a pulmonary cavity and its open- ing into the pleural cavity ; (4) The infection of the pleural cavity by the extension of a mixed infection from tuberculosis of the ribs or spine. A lung abscess complicating phthisis may communicate with a large bronchus and drain by means of cough and expectoration ; it may communicate with the pleural cavity ; and it may communicate with both with the bronchus and the pleural cavity. The bacteriology of empyema and lung abscess is apt to be very complicated unless treatment is applied early when the bacteria concerned in the etiology of the infection decidedly predominate and are easily recognized. The fol- lowing are the bacteria which are mainly concerned in these processes : Streptococcus Pneumococcus M. catarrhalis M. tetragenus B. Friedlander B. coli B. proteus Staphylococcus B. pyocyeneus B. influenza 232 TUBERCULIN AND "VACCINE Treatment Treatment consists of three distinct measures whick should be applied together (" combined ") as each has its distinct indication. As is true in all forms of tuberculosis, treatment can only be effective in the largest number of cases when the combined methods are used. These methods are: \ r accines against the infection; Modified surgical measures for drainage or ;for the removal of purulent materials; Treatment of the condition for the prevention of reaccu- mulation of purulent material and for the stimulation of the healing process. Vaccines Against the Infection. The vaccine treatment of purulent effusions or pulmonary abscesses is the same as the vaccine treatment in acute pulmonary mixed infections both as to dosage and intervals (see page 193). However, the local treatment of the condition is far more important than the vaccine treatment. The purulent accumulation is so large in quantity that the bacterial growth can take place in spite of a sufficient immune response. The bacterial growth occurs beyond the reach of the defensive substances of the individual. When the antibodies do enter into the large effusions they become so diluted that only a small proportion of the invading organisms are reached. Modified Surgical Measures for Drainage or for the Removal of Purulent Materials. Although drainage is of primary importance in the treatment of both purulent effu- sions and pulmonary abscesses it is unnecessary to resort to radical surgical measures such as are employed where sur- gery is the only measure instituted for the relief of the condition. Through the application of the combined meas- ures for controlling the infection, the -removal of the puru- lent accumulation and the prevention of reaccumulation, the surgical measures can be greatly modified. It is sufficient to make a half inch incision under cocain or novocain anes- EMPYEMA AXD LUNG ABSCESS 233 thesia in an intercostal space for the passage of a medium sized catheter through which the purulent effusion may be aspirated, using for this purpose either a syringe or vacuum suction. Through the same catheter, warm sterile normal saline should be injected several times and again aspirated in order to wash out the abscess or pleural cavity. This procedure should be repeated daily until the fluid with- drawn is no longer purulent. Local Treatment for the Prevention of Reaccumulation of the Purulent Materials and for the Stimulation of the Healing Process. After the abscess or pleural cavity is emptied and w r ashed of purulent material, sterile olive oil should be injected and left in the cavity until the next treat- ment. The quantity of olive oil injected should be about one-half of the amount of purulent fluid withdrawn, except in cases where the pulmonary abscess communicates with the bronchus. In that case the olive oil should be injected until coughed up through the mouth. The distress and vomiting produced by the foul discharge coming up through the bronchus almost entirely disappears after the injec- tion of olive oil. In cases of purulent pleurisy and in cases of pulmonary abscess where the communication with the bronchus still exists, vaccines, cleansing, and olive oil injections are sufficient. In case of a pulmonary ab- scess which becomes adherent to the parietal pleura and communicates directly with the surface of the body, and where the communication with the bronchus has healed over or never existed, bismuth paste should be employed. Be- ginning with Formula 1 bismuth paste (page 219) the subse- quent injections should be made with the stronger formulas if no tendency of bismuth poisoning has appeared. By means of olive oil injections the bismuth can be easily washed out in case of poisoning. In the following three illustrations will be found typical examples of each of the three different forms of pulmonary abscesses: one communicating with the pleura and produc- TUBERCULIN AND VACCINE ing a purulent pleurisy; one communicating with the bronchus allowing of vaccine treatment only ; one com- municating with both the pleura and bronchus. I have added a fourth illustration to emphasize the necessity of radiography for the diagnosis of these conditions. This patient was pronounced hopeless on account of a pulmonary abscess and purulent effusion, whereas the radiograph dis- closed the existence of an extra pleural pus cavity leading above to the diseased vertebra and running down to the pelvis. FIG. 56 A young woman twenty-four years old had pulmonary tuberculosis for four years, and in spite of change of climate, hygienic and dietetic treatment, the disease progressed until there was involvement of the apex of the right lung and of the jentire left lung with a cavity in the middle of the left lung. Two years pgo she was brought to me for tuberculin and vaccine treatment. On examination her case seemed hopeless, but fearing that my refusal of treatment would disclose the hopelessness of the condition to the patient and thus hasten her death, her relatives requested me to treat her with tuberculin irrespective of my prognosis. My fear was that the three trips a week to my office in order to get the treatment would overtax the strength of the patient in her already weakened condition. However, the renewed hope for cure, together with a marked response to the tuberculin treatment had a wonderful effect on the patient. After a year and a half of the treatment she had gained in weight, was much stronger so that she was able to attend to all her household duties. She still had a morning cough productive of sputum, but the amount of sputum was greatly diminished and the tubercle bacilli had disappeared entirely five months after beginning the treatment. The X-ray findings at this time showed the right lung greatly enlarged through emphysema, the left lung greatly contracted and the cavity, though still present, somewhat smaller. After the conclusion of tuber- culin treatment, and contrary to instruction, she did not return at the end of three months for the test for the return of hypersusceptibility, and for the examination of sputum for determining the renewal of the vaccine treatment. Six months later I was called to her home and found that she had had an attack of grippe and for seven weeks had a daily temperature rise to 103 or 105 F. The doctor in attendance had pronounced her .condition hopeless for he could "hear no breathing sounds in the left lung and considered it a case of tubercular pneu- monia. As three weeks had passed and the patient was still in the same condition, I was called in for consultation. The first glance at the patient was sufficient to discover that the left pleural cavity was tre- EMPYEMA AXD LU^G ABSCESS 235 memiously distended with fluid. Examination showed that her heart pushed to the right, and the chest which had been retracted on the left side was now decidedly bulging. An aspirating needle brought out a very thick foul smelling pus. Owing to the cyanotic and dyspneic condition of the patient, I decided to drain the pleural cavity at once. After cocain infiltration, a stab incision was made in the seventh interspace on the left side of her back. Ninety-eight ounces of pus were withdrawn, and through a soft rubber catheter one quart of sterile olive oil was injected. For the next ten days the pleural cavity was emptied through this catheter, washed out with normal' saline and refilled with a constantly decreasing amount of sterile olive oil. At no time was a drain of any kind left in the incision. Two days after the incision was made the temperature dropped to normal and remained there. The above radiograph was taken one month after the discontinua- tion of all local treatment of the abscess. It corroborated the earlier conclusion that the cavity had ulcerated through and broken into the pleural cavity, that the lung had become adherent to the pleura after the pus had been withdrawn, and that the lung cavity is in direct com- munication with the external fistulous opening. The bismuth paste which was injected for this X-ray photograph entered directly into the lung abscess. An important point which this case brings out is the fact that the communication between the original lung cavity and the bronchus healed across immediately after the drainage of the pleural cavity. The cough and expectoration which persisted after the tuberculin and vaccine treatment now disappeared. The patient declares that she is better than she has ever been since the beginning of her illness. The most prominent bacteria found in the pus of the pulmonary abscess, and for which vaccines were made were the streptococcus, m. catarrhalis and the pyocyaneus. 236 TUBERCULIN AND VACCINE FIG. 57. Over a period of four years this patient had repeated attacks of " pneumonia " lasting from one to three weeks, and characterized by bloody sputum, high temperature and dyspnea. Each attack left him with a severe cough which was productive of. a large amount of foul smelling expectoration, and which lasted for varying lengths of time. Every time the cough ceased there would be a fresh attack of " pneu- monia." The fifth attack was accompanied by an unusual amount of blood in the expectoration leading to the diagnosis of tuberculosis and the reference of the case to jme. The nature of the patient's tempera- ture curve was typical of pyemia. His temperature ranged from normal in the morning to 103 and ,105 F. in the afternoon. There was distinct dullness over the middle right lung, and it had been noticed that all the pneumonic proceses always localized in the same place and never spread beyond it. This temperature curve, the patient's history, and character of his sputum led to the diagnosis of lung abscess draining through a bronchus. The X-ray confirmed this diagnosis. An autogenous vaccine was made of the streptococcus and pneumo- coccus found in the sputum, and after the first dose of forty million streptococcus and twenty-five million pneumococcus, the temperature came down to normal. Although it may be claimed that the tempera- ture came down after the establishment of proper drainage through the bronchus, as in previous attacks, it cannot be denied that the complete healing was brought about by the vaccine. That the patient is cured is evidenced by a gain of over twenty-five pounds in weight, the disappearance of the cough and expectoration soon after the tem- perature was reduced to jnormal. Although there was no recurrence of " pneumonia " for over a year, a course of tuberculin treatment was also administered as the original cause of the abscess was no doubt tubercular in nature. During the tuberculin treatment the tubercular process in the apex of the right lung and in the upper half of the left lung cleared up. The above radiograph was taken after the expectoration became profuse and the abscess had more or less emptied. The abscess would show more distinctly if the radiograph had been taken two days earlier. FIG. 57. Pulmonary abscess draining into a bronchus. EMPYEMA A^D LUNG ABSCESS 237 FIG. 58. During a mild tubercular lesion in the apex of the right lung the patient suffered an attack of lobar pneumonia involving the entire right lung. This attack terminated by lysis and finally developed into a typical case of unresolved pneumonia which after six weeks was finally recognized as a pulmonary abscess. The temperature at this time was of the septic type rising daily to 104 and 105 F. with marked dysp- nea. An Estlander operation was immediately advised but the patient's family refused on account of the bad prognosis rendered by a number of physicians. When I first saw the patient he was in the most desper- ate condition, cyanosis and dyspnea were marked. He was greatly emaciated not only on account of his disease but on account of his inability to partake of any kind of food. His expectoration was so copious and so foul smelling that it would bring about gagging and vomiting after any attempt at swallowing. He presented such a poor subject for a radical operation, that I had no hesitancy about offering as good a prognosis with conservative treatment. At the New York Polyclinic Hospital I made a one-half inch incision under local anes- thesia in the sixth intercostal space two and a half inches to the right of the spine. The foul smell of the discharge which drained through this incision drove all the attendants out of the operating room. The predominant organisms were the streptococcus and pneumococcus. An autogenous vaccine was immediately made. In spite of daily cleansing and profuse drainage through the incision the patient continued to bring up large quantities of pus. After three or four inoculations with the autogenous vaccine, however, the discharge changed and became mucoid instead of purulent. A smear made of the pus at this time showed none of the offending organisms. The temperature came down to normal. After five weeks in the hospital the patient was able to leave and to come to my office for treatment of the local condition of the ab- scess. Bismuth paste treatment was not thought advisable, but after the injection of a ten per cent, bismuth paste for diagnostic purpose, distinct bismuth poisoning appeared (one of the only two eases of bismuth poison- ing I have ever seen). Owing to the discovery of the lead line at the gin- gival margins of the teeth, olive oil was used in order to wash out the bismuth paste. Several ounces of the olive oil were injected through the incision and then aspirated with the bismuth paste. This was re- peated two or three times until the aspirated oil showed no further trace of bismuth, and to make certain, olive oil was injected and left in the abscess cavity to drain out slowly in order to carry with it any traces of bismuth that might have been left. It was thought necessary for this purpose to entirely fill the abscess cavity, hence the injection was continued until the patient complained of distension. Suddenly he began to cough and brought up a quantity of olive oil through the bronchus. Three days later he returned to the office with the report that on the second day after his lat treatment he could not " taste " the smell of the pus and was therefore able to eat for the first time in months with- 238 TUBEBCULIN AND VACCINE out vomiting. As the pus reappeard on the third day, he had returned for another olive oil injection, which was given in the same manner as before and until it produced the expectoration of olive oil. Several days of comfort followed. All other treatment was abandoned and the olive oil injections repeated every third day. After six such injections, the oil was not coughed up and the cough and expectoration stopped entirely. After three more injections of the olive oil the quantity of which was constantly diminishing in amount, the incision healed and the patient was cured as far as the pulmonary abscess was concerned. During the four weeks of treatment with olive oil he gained nine pounds in weight, and in the four months following the healing of the abscess he gained thirty pounds more. Unfortunately the X-ray picture which was taken after the bismuth injection and which distinctly showed the communication of the bronchus with the external incision was lost. The radiograph repro- duced here shows the contracted cavity representing the healed condi- tion a year after the complete cure of the patient. This is the first instance where I used olive oil in chest conditions, and I have used it ever since with equal success. EMPYEMA AND LUNG ABSCESS 239 FIG. 59. This girl, twenty-three years old, with a negative family history, had laryngeal diphtheria at the age of six, and at eleven pneumonia and pleurisy. After the attack of pleurisy she could not walk without limping and the tubercular condition of her right hip soon manifested itself. A plaster cast was applied and worn for about a year, and then replaced by a brace which she has worn ever since. Two years later, her mother noticed a protruding dorsal vertebra. A spinal brace was applied, but in spite of it pain developed in the spine, which increased in severity until four years later when it confined her to bed. A Hibb's modification of the Albie operation was performed and for about one year she was relieved. Then the pain recurred all around the body at the waist line, in the ribs and back, and finally radiated down into the left leg and she was again unable to walk. Eight months later a fistula broke open three inches to the left of the spine at the lower border of the twelfth rib, discharging a purulent matter ever since. As soon as this discharge began, the pain, disappeared from the leg and she was again able to walk. In December, 1916, she caught cold, pleuritic irritation and a con- stant irritating cough developed. Any attempt at speaking produced a fit of coughing and shortness of breath. Shortly after dyspnea and cyanosis developed. Since March 9, when she first began to take her temperature it ranged between 100 and 104 F. She was at this time sent to a hospital for advanced pulmonary tuberculosis, and the family were told that her condition was hopeless as the disease had extended to her lungs where ifc had produced a pulmonary abscess and empyema. Four weeks previous to this writing I first saw this patient. On the earnest solicitation of her family I undertook her treatment. The above X-ray disclosed the condition to be entirely outside of the pleural cavity, the accumulation of the purulent material producing the cough and dyspnea through pressure. The pus, on examination, disclosed streptococcus and staphylococcus albus to be the principal causes of the infection. Vaccine treatment and the establishment of a counter opening near the superior border of the ileum through which bismuth paste is injected, has improved her condition by reducing her tempera- ture to almost normal, and the amount of purulent discharge reduced to less than one-quarter of the amount formerly discharged. This improvement, together with the psychological effect brought about by the discovery that her lung was not affected, has produced a remark- able effect on her general well-being. The many hours of tireless work which I bestowed upon the preparation of this work will not prove in vain if I have succeeded, at least in some measure, to stimulate the spread of the use of tuberculin and vaccine in the treatment of tuberculosis in general practice. Certain it is, that the conquest of this wide-spread dis- ease lies in the hands of the general practitioner, and it is equally certain that the final utilization of the immune response is the best weapon against this scourge. That the signs of the times point to the awakening of the medical profession to these truths, I can give no better proof than to quote from Bandelier and Roepke, in the conclusion of their work "Tuberculin in Diagnosis and Treatment" After citing examples from many localities of the successful institution of tuberculin treatment in general practice, they conclude by saying: "Were we to add the names of all the practitioners who, by word of mouth or in writing, have acquainted us with their reliance on tuberculin therapy, we should only tire the reader. We content ourselves with the recogni- tion that this is the sign of a realization of what is really necessary in the fight against tuberculosis. For tubercu- lin will not be used to its full advantage and its far-reach- ing importance realized if, excluding the sanatoria, merely a few doctors make use of it. No! Tuberculin* must be an integral part of the medical equipment of every physician. It must be the Alpha and Omega of our diag- nosis, prophylaxis, and therapy of tuberculosis. Then it will fulfil its destiny to assist in the extirpation of the disease. And in conclusion we may hopefully give ex- pression to the conviction that our conception of the far- reaching importance of the specific diagnosis and therapy of tuberculosis will soon be the common property of &11 medical men." BIBLIOGKAPHY ALLEX. ' ' The Bacterial Diseases of Eespiration, and Vaccines in Their Treatment." (New York, 1913.) AMBREIN. "Beitrage z. Klinik d. Tuberk. u. spez. Tuberkulose For- schung." (1912, Bd. xxiii, Heft 2.) "Weitere Tuberk. Erf ahrungen. " (Beitrage zur Klinik der Tu- berkulose, 1907, viii, 327.) ANDERSON. "A Plea for the More General Use of Tuberculin by the Profession. *' (Brit. Journ. of Dermatology, 1905, xvii, 317.) AUFRECHT. '*Pathologie und Therapie der Lungenschwindsucht. " (Vienna, 19U5.) AUGSTEIX. "Zeitschr. fur Bahniirzte." (1911, Xr. 6.) BAIL. " tlbertragung der Tuberkulinempfindlichkeit. " (Zeitschr. f. Immunitatsforschung, 1910, liv, 470.) BALDWIN. "General Principles of Tuberculin Diagnosis and Treat- ment.." (J. Am. M. Ass., Chicago, 1910, liv, 260.) BAXDELIER. Opened discussion: "Stand der spezifischen Behandlung der Tuberkulose." (IV. Versamml. der Tuberkulose Arzte, Berlin, 1907.) "Die Leistungsfahigkeit der kombinierten Anstalts und Tuber- kulinbehandlung bei der Lungentuberkulose. " (Beitrage zur Klinik der Tuberk., 1910, xv, 1.) BANDKLIER and ROPKE. "Tuberculin in Diagnosis and Treatment." (New York, 1913.) BAR and DESSAIGXE. "De 1'epreuvc de la tuberculine chez la femme enceinte." (La presse me'dieale, 1911, xix, 147.) BECK. "Bismuth Paste in Chronic Suppuration." (St. Louis, 1914.) BEXIXDE. "Zur Frage der ambulanten Tuberkulin-therapie. " (Deutsche med. Wochenschr., 1910, xxxvi, 1080.) Gesundheit, 1909, Xr. 18. BERAXECK. "La tuberculine Beraneck et son mode d 'action. " (Rev. med. de la Suisse Rom., 1907, xxvii, 444.) ' ' Le traitement de la tuberculose par les tuberculines, et plus specialement par la tuberculine Beraneck." (Tuberculosis Congress, Washington, 1908, Trans, i, 724.) ' Beraneck 's Tuberculin and its Method of Application." (Edinb. M. J,, 1909, n.s. iii, 522.) V. BERGMAXX. ' ' Die Behandlung des Lupus mit dem Koch 'schen Mittel." (Samml. Klin. Vortrage, 1890-94, 126.) BERTIER. ' ' Recherches sur la baeillurie tuberculeuse au cours de la tuberculose pulmonaire. " (Zeitschr. f. Tuberkulose, 1910, xvi, 386.) BIEK. "Textbook of Hyperaemia." By August Bier, translated by Dr. G. Blech. 1909.) 16 242 BlBLIOGEAPHY BONIME. "Tuberculin in Surgical Tuberculosis." (N. Y. Med. Journ. April 15, 1916.) "The Immune Response in Pulmonary Tuberculosis." (Ibid., May 13, 1916.) "Vaccines in Acute Infection." (Med. Eec., Aug. 12, 1916.) "A Simplified Technique in Tuberculin Administration." (Ther. Gaz., June, 1917.) BOHME. Munch, med. Wochenschr., 1909, Nr. 22 u. 23.) BINSWANGER. Arch. f. Kinderheilk., 1906, Bd. xi, Heft. 1-4.) BIRNBAUM. "Das Koch'sche Tuberkulin in der Gynakologie und Ge- burtshilfe." (Berlin, 1907.) Verlag von Springer. Zentralbl. f. Gynak., 1907, Heft 39. BOSANQUET and EYRE. "Serums, Vaccines and Toxines." (2nd ed., London, 1910.) BRIEGER. "Uber die Einwirkung des Kocih'schen Verfahrens auf Schleimhautlupus." (Deutsche med. Wochenschr., 1891, xvii, 200.) BROOKS and GIBSON. "A case of retrogressive Tuberculous Menin- gitis." (Lancet, 1912, ii, 815.) BROWN. "Specific Treatment." (Tuberculosis, ed. by A. C. Klebs, London, 1909.) BRYAN. "Serum and Vaccine Therapy in connection with Diseases of the Eye." (Brit. Med. Journ., 1912; j, 589.) BULLOCH. "The Treatment of Tuberculosis by Tuberculin." (Lancet, 1905, ii, 1603.) BUMM. Sitzungsbericht des Ausschusses des Deutschen Zentral- komitees. Mai, 1910. BUSSENIUS. "Einige Mittheilungen iiber die bisher bei Anwendung des TE Tuberkulins jgesammelten Erf ahrungen. " (Deutsche med. Wochenschr., 1897, xxiii, 441.) BUTLER. "On Tuberculo-toxaemia of the Eye, and on the Thera- peutic and Diagnostic Value of Injections of Tuberculin in its Treatment and Diagnosis." (The Ophthalmoscope, 1910, viii, 867.) CARMALT- JONES. "A Review of the Inoculation Treatment of Tuber- culosis." (Brit. Med. Journ., 1909, ii, 531.) CASPER. Introd. discussion : ' ' Diagnose und Behandlung der Blasen und Nierentuberkulose. " ,(VL Versamml. der Tuberkulose Arzte, Berlin, 1909.) CEVEY. "Les Tuberculin es et le Traitement Specifique de la Tuber- culose." (Rev. med. de la Suisse Rom., 1908, xxviii, 677 and 757.) . CHAMBERS and Russ. "The bactericidal action of Radium Emana- tion." (Proceedings of Roy. Soc. of Medicine, 1912, V. Patho- logical Section, 198.) CITRON. "Kritisches und Experimentelles zur Tuberkulintherapie. " (Berlin klin. Wochenschr., 1909, xlvi, 2288.) Deutsche med. Wochenschr., 1912, Nr. 20. BIBLIOGRAPHY 243 CLARK. "The Street Tuberculin Dispensary." (Pub. Health, London, 1911, xxiv, 273.) , CORNET. "Die Tuberkulose " p. 1010, 2nd ed. (Vienna, 1907.) CROWE. "A New Method of Treating Acute Phthisis by the Alter- nate Use of Human and Bovine Tuberculin." (Lancet, 1910, i, 1130.) 'A Series of One Thousand Inoculations, chiefly in Private Prac- tice." (Brit. Med. Journ., London, 1911, i, 128.) DAVIDS. Klin. Monatsbl. f. Augenheilk., 1909, Bd. xlvii (Neue Folge Bd. vii, v. Graefes Archiv f. Ophthalmolog-ie, 1908, Bd. Ixix, Heft 2.) DENYS. "Le Bouillon Filtre du Bacille de la Tubereulose dans le Traitemenjt ide la Tuhercujosie Humaine. " (Louvain and Paris, 1905.) ' ' ' The Filtered Bouillon of the Human Tubercle Bacillus as an Agent for Specific Treatment of Tuberculosis in Man." (Tu- berculosis Congress, Washington, 1908, Trans, i. 749.) DERBY and AYER. "A Clinical Investigation on the Eelationship of Tuberculosis to Certain Diseases of the Eye." (J. Am. M. Ass., Chicago, 1910, liv, 1762.) DOUTRELEPONT. " Kurze Mittheilung iiber die bisherigen Erfahrungen bei der Anwendung des neuen Koch'schen Tuberkulins. " (Deutsche med. Wochenschr., 1897, xxiii, 537.) EHRLCIH. International. Kongr. fiir Hygiene, 1903. EHRLICH and GUTTMANN. Deutsche med. Wochenschr., 1891. ELLERMANN and ERLANDSEN. t)ber quantitative Ausfiihrung der kutanen Tuberkulin Eeaktion. " (Deutsche med. Woehenschr. 1909, xxxv, 436.) ' ' Das Gesetz der kutanen Tuberkulin Eeaktion und ihre An- wendung bei der Standardisierung von Tuberkulin." (Beitrage zur Klinik der Tuberkulose, 1910, xvi, 1.) ESCHERICH. t)ber Indikationen und Erfolge der Tuberkulintherapie bei der kindlichen Tuberkulose." (Wien. klin. Wochenschr., 1910, xxiii, 723.) FAIRLEY. "On the Work of the Portsmouth Tuberculin Dispensary." (Public Health, 1912, xxv, 376.) FORBES and BANKS. ' ' Sterile abscesses following the use of Tuber- culin." (Lancet, 1912, o. 1338.) FRAZER. "Eeport on Sanatorium and Tuberculin Treatment together with a description of the Portsmouth Municipal Tuberculin Dispensary." (Portsmouth, 1911.) FRAZER and CLARK. "The Municipal Dispensary and Tuberculin Treatment." (Jour, of the Boy, San. Inst., 1912, xxxiii, 390.) FREYMUTH. "t)ber Anwendung von Tuberkulinprap. per Os." (Munch, med. Wochenschr., 1905, lii, 62.) "Erfahrungen mit eiweissfreiem Tuberkulin." (Beitrage zur Klinik der Tuberkulose, 1911, xx, 215.) 244 BIBLIOGRAPHY FKIEDBERGER. Med. Klinik, 1910, Nr. 13. Deutsche med. Wochenschr., 1911, Nr. 11. Zeitschrift fur Immunitatsforschung und experimentelle Ther- apie, 1909-1911. FRIEDBERGER, SZYMANOWSKI, KUMAGAI and ODAIRA, LURA. Zeitschrift f. Immunitatsforschung und experimentelle Therapie. Bd. xiv, Heft 4, 1912. FRIEDEMAXX. "t)ber passive Uberempfindlichkeit. " (Munch, med. Wochenschr., 1907, liv, 2414.) GABKILOWITSCH. ' ' The Treatment of Pulmonary Tuberculosis with Tuberculinum Purum." (Tuberculosis Congress, Washington, 1908, Trans, i, 221.) "t)ber das Tuberculinum purum." (Zeitschr. fur Tuberkulose, 1908, xiii, 234.) GAXGHOFXER. ' ' t)ber die therapeutische Verwendung des Tuberkulins in Kindesalter. " (Jahrbuch. f. Kinderheilk, 1906, Ixiii, 525.) GOTSCH. Uber /lie Behandlung der Lungentuberkulose mit Tuber- kulin." (Deutsche med. Wochenschr., 1901, xxvii, 405.) GRAY. "Vaccine Treatment in Surgery." (Lancet, 1906, i, 1099.) HAMBURGER. "Allgemeine Pathologic und Diagnostik der Kinder- tuberkulose. " (Vienna, 1910.) HAMBURGER and MONTI. "Die Tuberkulosehaufigkeit im Kindesalter." (Munch, med. Wochenschr., 1909, Ivi, 449.) HAMMAX and WOLMAN. "Tuberculin Treatment among Dispensary Patients." (Johns Hopkins Hospital Bull., 1909, xx, 225.) HAMMER. "Die Tuberkulinbehandlung der Lungentuberkulose." (Beitriige zur Klinik der Tuberkulose, 1907, vii, 179.) HAWES and FLOYD. "The Tuberculin Treatment of Dispensary Pa- tients." (Boston Med. and Surg. Journal, 1910, clxii, 1.) ' ' The Use of Tuberculin in the Early Diagnosis of Tuberculosis in a Large Out-patient Clinic." (Boston Med. and Surg. Journ., 1907, xlvi, 694.) HAYASHI. "t)ber einen bemerkenswerten Fall von Tuberkulose des Auges mit Sektionsbefund. " (Klin. Monatsbl. f. Augenh., 1911, n.s. xi, 274.) HELWES. (Zeitschrift fur Medizinalbeamte, 1912. Berichte, S. 108.) HEROX. ' ' On Koch 's Treatment in Tuberculosis of the Lung and in Lupus Vulgaris." (Lancet, London, 1891, Ixix, i, 920 and 974.) "A Lecture on the Treatment of Consumption and of Lupus by Tuberculin." (Brit. M. J., London, 1898, ii, 76.) Introduced Discussion on the Therapeutic and Diagnostic Value of Tuberculin in Human Tuberculosis. (Brit. Congr. Tuber- culosis, 1901, Trans, iii, 84.) HEWLETT. "The Effect of the Injection of the Various Tuberculins and of Tubercle Endotoxin on the Opsonic Action of the Serum of Healthy Babbits." (Roy. Soc. of Medicine Proc., 1910,. iii, Path. sect. 165.) BIBLIOGRAPHY 245 HILLEXBERG. ' ' Weiterer Beitrag zur Entstehung und Verbreitung der Tuberkulose." (Tuberculosis, 1911, x, 254.) V. HIPPEL. ' ' Uber den Nutzen des Tuberkulins bei der Tuberkulose des Auges." (Archiv. fiir Ophthalmol., 1904, lix, 1.) HOLLMANN. "Uber den Verlauf von Tuberkulinreaktionen bei Tag und bei Nacht. " (Beitrage zur Klin, der Tuberkulose, 1911, xxi, 127.) VAN HOORX. ' ' Uber das neue Tuberkulin TR bei der Behandlung des Lupus und der Blasentuberkulose. " (Deutsche med. Wochensch., 1897, xxiii, 625.) HORT. ' ' Rational Immunization in the Treatment of Pulmonary Tu- berculosis. " (London, 1909.) ' ' Tuberculin in the Diagnosis and Treatment of Tuberculosis. ' ' (Quart. Journ. of Med., 1911, vi, 377.) HUDSON. ' ' The Practical Use of Vaccine Treatment in Pulmonary Tuberculosis." (Lancet, 1912, ii, ,1148.) JAXXSEN. "Einige charakteristische Falle von Entfieberung mit Tu- berkulin." (Bericht der Deutschen Heilstatte, Davos, 1910.) JOCHMANN. ' ' Uber die spezifische Behandlung der Tuberkulose mit Tuberkulin-prap. ' ' (Kougr J fur ttnnere Medizin, Wiesbaden, 1910.) JOSEPH. "Zur Theorie der Tuberkulin-Uberempfindlichkeit." . (Beit- rage zur Klinik der Tuberkulose, 1910, xvii, 461.) KARO. Contrib. to discussion : ' ' Diagnose und Behandlung der Blasen und Nierentuberkulose. " (VI. Versamml. der Tuberkulose Arzte, Berlin, 1909.) "Klinische Erfahrungen mit der Kombinationstherapie der Nieren- tuberkulose. " (Tuberculosis, 1911, x, 273.) KING. , "Vaccine Therapy in Tuberculosis." (New York Med. Journ., 1910, xcii, 164.) KOCH, "liber bakteriologische Forschung." (Tenth Internat. Med. Congr., Berlin, 1890 ref. Centralbl. fur Bakteriol, viii, 563.) ' ' Weitere Mittheilungen iiber ein Heilmittel gegen Tuberkulose. ' ' (Deutsche med. Wochenschr., 1890, xvi, 1029) ; supplementary papers (ibid. 1891, xvii, 101 and 1189.) "Mittheilung Uber neue Tuberkulinprap. " (Ibid. 1897, xxiii, 209.) "Uber die Venvertung dieser Agglutination." (Ibid. 1901, xxvii, 829.) KOSSLER and NEUMANN. "Opsonischer Index und Tuberkulose-therapie nebst Beitragen zur Technik und Dosierung der Tuberkulin- injektionen. " (Wiener kliii. Wochenschr. 1909, xxii, 1547.) KRAMER. "Tuberkulin und Nierentuberkulose. " (Zeitschr. fiir Urolog., 1909, iii, 942.) KRAUSE. "Die Tuber kulintherapie in der ambulanten Behandlung und bei Fiebernden. " (Miinchn. med. Wochenschr. 1905, iii, 2523.) "Uber innerliche Amvendung von Kochs Bazillen-emulsion (Phty- soremid)." (Zeitschr. fUr Tuberkulose, 1907, x, 508.) 246 BIBLIOGRAPHY "Interne Anwendung von Tuberkulin." (Ibid. 1909, xiv, 73.) " Entfieberung mit Bazillenemulsion. " (Zeitschr. fur Tuberku- lose, 1909, xv, 284.) KUMMELL. "Die chirurgische und spezifische Behandlung der Nieren- tuberkulose. " (82 Versamml. deutseher Naturforscher und Arzte. Kb'nigsberg, 1910.) LANDMANN. Zentralblat fiir Bakteriologie, Bd. xxvii, 1900. Hygienische Rundschau, 1898, Nr. 10 u. 1900, Nr. 8. LATHAM. "The Uses of Tuberculin in Pulmonary Tuberculosis." (Lancet, 1912, i, 1109.) LATHAM and INMAN. "A Contribution to the Study of the Admin- istration of Tuberculin in Pulmonary Tuberculosis." (Lancet, 1908, ii, 1280.) LATHAM with SPITTA and INMAN. ' ' Preliminary Communication on the Administration of Tuberculin (TR) and other Vaccines by the Mouth." (Roy. Soc. of Medicine Proc., 1908, i, Med. Sect. 195.) V. LEUBE. Munch. Med. Wochenschr., Nr. 31, u. 32. LEVY. "Uber die ersten Falle von Lupus der ausseren Haut, welche mit Tuberkulin behandelt wurden. " (Verhandl. d. Deut. Gesell. f. Chirurg., 1891, xx, i, 88.) LITZXER. ' ' Die Tuberkulinbehandlung der chronisehen Lungentuber- kulose." (Zeitschr. fur. Tuberkulose, 1910, xvi, 60.) "Die Dosierung des Tuberkulins. " (Ibid. 1911, xvii, 549.) Low. ' ' Tuberculin as an aid to Diagnosis and Treatment. ' ' (Brit. Journ. of Dermatol., 1906, xviii, 189.) LQWENSTEIN. "Die innerliche Darreichung des Alttuberkulins. " (Zeitschr. fiir Tuberkulose, 1906, ix, 392.) ' ' Die Behandlung der Lungentuberkulose -nach Robert Koch. ' ' (Therap. Monatschr., 1909, xxiii, 593.) LUDKE. "Uber die diagnostische und therapeutische Verwertung des Alttuberkulins in der in tern en Praxis." (Wiirz-Abhandl. vii, part 9.) i MANTOUX. "L'intradermo-reaction a la tuberculine et son interpreta- tion clinique." (La Presse MSdicale, 1910, xviii, 10.) "Le traitement par la tubereuline des tuberculoses urinaires." (Ibid. 1910, xviii, 705.) MANTOUX and LEMAIRE. " Intradermo-reaction a la tuberculine chez 300 enfants non malades." (Semaine mgdicale, 1909, xxiv, 371.) MAMOREK. Berliner klin. Wochenschr., 1903, Nr. 48. Med. Klinik, 1906, Nr. 3. Sitzung d. Berliner med. Gesellsch., v. 8, v. 1907.) XI Congres frangais de me'deeine, Paris, Octobre, 1910. La presse m6d., 1910, Nr. 89. MARTIN. "The occurrence of Remissions and Recovery in Tuberculous Meningitis." (Brain, 1909, xxxii, 209.) MEISSEN. " Tuberkulinproben und Tuberkulinkuren. " (Zeitsehr. fiir Tuberkulose, 1908, xiii, 199.) BlBLIOGEAPHY 24:7 MEYER and SCHMITZ. "tjber das Wesen der Tuberkulinreaktion. " (Deutsche med. Wochenschr. 1912, xxxviii, 1963.) MILLER. "The Tuberculin Treatment of Pulmonary Tuberculosis in Office and Dispensary Practice." (Trans, of the Congress of American Physicans and Surgeons, 1910, viii, 126.) MITULESCU. ' ' Spezifische Substanzen in der Diagnose und Behandlung der Tuberkulose." (Berlin klin. Wochenschr. 1909, xlvi, 1477 and 1536.) MQLLER and LQWEXSTEIN and OSTROVSKY. ( "Une nouvelle mSthode de diagnostic de la tuberculose pulmonaire par la tuberculine de Koch." (C. R. du Congres inter nationale de la Tuberculose, Paris, 1905, 1906, i, 373.) , MOLLER. ""Qber interne Anwendung, von Tuberkulin und tuberkulin- ahnlichen Prap." (Munchn. med. Wochenschr. 1908, iv, 2324.) MQLLERS and HEINEMANN. "tjber die stomachale Anwendung von Tuberkulinprap. " (Deutsche, med.' 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(Bos- ton Med. and Surg. Journ., 1907, clvii, 621.) PARDOE. ' ' The Treatment of Tuberculosis of the Urinary System by Tuberculin T.R." (Lancet, 1905, ii, 1766.) PAWLOWSKY. ' ' Zur Frage iiber die Immunisierung gegen Tuberkulose und die Serum-behandlung der Tuberkulose. " (Eussky Vratsch, 1910, Nos. 14-16.) PENZOLDT. "Die Spezifische Erkennung und Behandlung der Tuber- kulose beim Mensehen." (Kongr. fur innere Medizin, Wies- baden, 1910.) "Uber den Krankheitsverlauf bei vor 19 Jahren mit Tuberkulin behandelten Lungentuberkulosen. " (Deutsche Archiv. ftir klin. Medizin., 1910, c. 68.) 248 BIBLIOGRAPHY PETRUSCHKY. "Die Behandlung der Tuberkulose nach Koch." (Deutsche med. Wochenschr. 1897, xxiii, ,620 and 639.) "Vortrage zur Tuberkulose-bekampf ung. " (No. 1, Leipzig, 1900.) ' ' Koch 's Tuberkulin und seine Anwendung beim Menschen. ' ' (Berliner Klinik, 1904, clxxxviii.) . t "Specifische Behandlung der Tuberkulose." (Tuberculosis Con- gres, Washington, Trans, i, 790.) PFEIFFER and LEY ACKER. ' ' Versuche iiber die "Wirksamkeit innerlich gegebener -Tuberkelbazillenpraparate. " (Wien. klin. Woch- enschr. 1910, xxiii, 1797.) PHILIPPI. ' ' t)ber Entfieberungen bei Lungentuberkulose dureh kleinste Dosen Tuberkulin." (Beitrage zur Klinik der Tuberkulose, 1910, xvi, 183.) PHILLIPS. ' ' Observations on two Cases of Lupus treated by Koch 's Tuberculin." (Brit. Journ. of Dermatol., 1891, iii, 121.) PICKERT. Deutsche med. Wochenschr., 1909, xxv, 1514. PICKERT and LQWENSTEIN. Deutsche, med. Wochenschr., 1908, xxxiv, 2262. POTTENGER. " Tuberculin in Diagnosis and Treatment." (St. Louis, 1913.) PREST. ' ' Fourth Annual Report of the Ayrshire Sanatorium, ' ' 1912. EADCLIFFE. Pathological Report. Fourth Annual Report, King Edward VII Sanatorium, Midhurst, 1909-10. Weber-Parkes Thesis, 1912. RAUDNITZ. Prague med. Wochenschr., 1907, xxxii, 439. RAW. ' ' The Treatment of Tuberculosis by different kinds of Tuber- culin." (Lancet, 1908, i, 481.) ROHMER. Archiv. f. Kinderheilk, 1910, Iii, 305. ROLLY. Miinchn. med. Wochenschr., 1910, Ivii, 833. ROMER. ' ' (jber intrakutane Tuberkulinanwendung zu diagnostisehen Zwecken." (Beitrage zur Klinik der Tuberkulose, 1909, xii, 185.) "Tuberkulose und Tuberkulin reaktion. " (Beitrage zur Klinik der Tuberkulose, 1910, CBii, 427.) ' ' Tuberkulose-Immunitat, Phthiseogenese und praktische Schwind- suchtbekiimpf ung. " (Beitrage zur Klinik der Tuberk., 1910, xvii, 383.) ROMISCH. ' ' t)ber Erf olge mit Tuberkulinbehandlung nach Gotsch 'schem Verfahren." (Miinchn. med. Wochenschr., 1902, xlix, 1913 and 1970.) "Uber Dauer erf olge mit Tuberkulinbehandlung." (Ibid. 1907, liv, 117.) ROSENHAUCH. ' ' t)ber das Verhaltnis phlyktanularer Augenentzundungen zur Tuberkulose." (Grafe's Archiv. fttr Ophthalmol., 1910, Ixxvi, 370.) ROSENTHAL. " Mittheilungen iiber die Behandlung des Lupus nach Koch." (Berlin klin. Wochenschr., 1891, xxviii, 143.) BIBLIOGRAPHY 249 ROTHSCHILD. "Uber Autotuberkuline. " (Zeitschr. ftir Tuberkulose, 1908, xii, 397.) "tJber Miscbtuberkuline. " (Deutsche med. [Woctensch,, 1909, xxxv, 921.) "Das Tuberkulin in der Hand des Praktischen Arztes. " (Wies- baden, 1910.) SAATHOFF. "Tuberkulin Diagnostik und Therapie nebst Stoffwechsel- untersuchungen bei der Tuberkulin-reaktion. " (Miinchn. med. Wochenschr., 1909, Ivi, 2041.) SAHLI. ' ' Tuberkulinbehandlung und Tuberkuloseimmunitat. ' ' 3rd ed. (Basel, 1910. English translation, 1912.) Contribution to Discussion on Tuberculin Treatment, Brit. Med. Ass., 1910. (Brit. M. J., London, 1910, ii, 1056.) SAXHORN. "The Place of Tuberculin in the Immunization of Tiro- genital Tuberculosis." (Boston Med. and Surg. Journ., 1910, clxii, 454.) SATA. (Zeitschr. fur Tuberkulose, 1901, ii, 43.) SAVOIRE. (La tuberculose, 1910, nos. 19-20.) SCHERER. (Discussion IV. Versammlung der Tuberkulose Arzte, Berlin, 1907.) SCHLOSSMANN. "Uber die therapeutischet Verwertung des Tuberkulins bei der Tuberkulose der Sauglinge und Kinder." (Deutsche. med. Wochenschr., 1909, xxxv, 289.) ScHNoLLER. ' ' Theoretisches und Praktisches tiber Immunisierung gegen Tuberkulose." (Strassburg, 1905.) SCHRODER. (Beitrage zur Klinik der Tuberkulose, 1909, xiv, 359.) SMITH. ' ' The Inoculation Treatment of Tuberculous Arthritis. ' ' (Brit. M.. J., 1909, ii, 1046.) SPENGLER. "Tuberkulinbehandlung im Hochgebirge. " (Davos, 1904.) SQUIRE. Essays on Consumption. (The Sanitary Publishing Co., 1900.) STARKLOFF. Beitrage zur Klinik der Tuberkulose, 1910, xvi, 225.) THOMSON. Medical Magazine, 1909, xviii, 441. TRUDEATJ. "Tuberculin Immunization in the Treatment of Pulmonary Tuberculosis." (American Journ. of Med. Science, 1907, cxxiii, 813.) "Antibacterial or antitoxic Immunization in Tuberculin Treat- ment." (Tuberculosis Congress, Washington, 1908, Trans, i, 796.) TRUDEAU, BALDWIN, and KINGHORN. Journ. of Med. Research, 1904, xii, 169. TURBAN. Eighth International Tuberculin Conference, Stockholm, 1909. VAUGHAN. "Zeitschr. f. Immunitatsforschung u. experiment." (Therap., Bd. i, Heft 2.) VOLLAXD. Zeitschr. f. Klin. Medizin, 1893, xxiii, 50. VOITURER. Med. Klinik, 1912, Xr. 46, p. 1886. WASSERMANN and BRUCK. Deutsche med. Wochenschr., 1906, Nr. 12. 250 BIBLIOGRAPHY WEDDY-PQNICKE. "tJber Tuberkulin-diagnostik, therapie und prophy- laxe in der ambulanten Praxis." (Zeitschr. fiir Tuberkulose, 1910, xvi, 422.) WEICKER. Wiener med. Wochenschr., 1907, Ivii, 2264. WESTERN. Lancet, 1907, ii, 1375. Brit. Journ. of Dermatology, 1909, xxi, 352. WHITE and GRAHAM. "A Quantitative Modification of the von Pirquet Tuberculin. Keaction and its value in Diagnosis and Prognosis." (Journ. of Med. Besearch, 1909, xv, 347.) WHITE and VAN NORMAN. Zeitschr. fiir Tuberkulose, 1901, xvi, 230. WHITFIELD. "On the Treatment of Skin Diseases by Inoculation after the Opsonie Method." (Practitioner, 1908, boot, 697.) WILDBOLZ. Berlin, klin. Wichenschr., 1910, xlvii, 1215. WILKINSON. "Tuberculin as a remedy in tuberculosis of the lungs." 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INDEX ABSCESS i PAGE Formation at site of inoculations 144 Cold 156, 226 ACCUMULATIONS, SERUS (see IRRITATIVE ACCUMULATION) ACTION OF BISMUTH PASTE 218 ACTIVE IMMUNITY 2 ACUTE Af ebrile mixed infections 177 Febrile mixed infections 173 Mixed infections 173 Pulmonary tuberculosis Ill Respiratory mixed infections 192 ADENITIS (see GLANDULAR TUBERCULOSIS) AF (ALBUMOSE FREE TUBERCULIN) 9 AFEBRILE- Acute mixed infection 177 Pulmonary tuberculosis 112 AGGLUTININS ; 4 ALLERGY 5 ANOPHYLAXIS 5 ANEMIA In bone disease 87, 213 ANGEL 's DOSAGE IN INTRACUTANEOUS TEST 34 ANIMAL INOCULATION FOR DIAGNOSIS . . . . , 162 ANTITOXINS 4 In tuberculosis 7 ANTIBODIES 4 ANTI-TUBERCULOSIS SERUM 7 APPLIANCES, ORTHOPEDIC 154 ARMY BEPORTS OF TUBERCULIN TEST 27 ASPIRATION \ In treatment of cold abscess 227 In treatment of soft glands 209 AUTOGENOUS VACCINE 170, 215 Advantages of 170 AUTOINOCULATION 145 Through exercise - 145 Through massage 145 Treatment of 147 BACILLARY BODIES 9 BACILLARY EMULSION (BE) 9 Method of making 9 In conclusion of treatment 13 252 INDEX PAGE BACTERIA Catarrhal 184 Pyogenic 184 BANDELIER & ROEPKE 35 BE (BACILLARY EMULSION) 9 BEGINNING TREATMENT In glandular tuberculosis 73 In lupus 140 In ocular tuberculosis 139 In tuberculosis of the ear 139 Of bone and joint tuberculosis 90 Of pulmonary tuberculosis Acute or Active 122 Chronic 117 Incipient 114 Of renal tuberculosis 103 Of tubercular peritonitis . . 133 BERANECK'S TUBERCULOL (TBk) 11 Bier 's hyperemia in 88 BlNSWANGER, REPORT ON THE DETERMINATION OF THE TUBERCULIN TEST 27 BISMUTH PASTE 86, 88, 217 Action of 218 Care of 219 Composition of 218 Counter openings for proper direction 223 Direction of .' 222 Formulas for 219 Frequency of treatment with 222 In bone and joint tuberculosis 86, 88, 217 In empyema 233 In lung abscess 233 Injections of 220 Retention of 221 Syringe 220 BONE CAVITIES J i Mixed infection in formation of 213 BONE AND JOINT TUBERCULOSIS 85 Anemia in 87, 213 Beginning treatment of (see BEGINNING TREATMENT) Bier 's hyperemia in 88 Bismuth paste in 86, 88, 217 Cavities, Sinuses and Fistulas in 213 Combined treatment of 89, 155, 213 Conclusion treatment of (see CONCLUSION TREATMENT) Genera] hypersusceptibility in 90 INDEX 253- BONE AND JOINT TUBERCULOSIS Con. PAGE Irritative accumulations in 88 Mixed infection in (see MIXED INFECTION) Eesults of treatment in 92. Vaccines in (see VACCINES) CALCAREOUS PULMONARY TUBERCULOSIS Ill CALMETTE'S CONJUNCTIVAL TEST 35 CARE OF Bismuth paste 219 Vaccines 168 CATARRHAL PROCESSES IN PULMONARY MIXED INFECTIONS 184 CAUSATIVE ORGANISM Diagnosis of 161 CAVITY, BONE Formation of 213 Mixed infection in 213 CERVICAL ADENITIS (see GLANDULAR TUBERCULOSIS) CHRONIC Mixed infections 179 Pulmonary tuberculosis 110 Kespiratory mixed infections 186 CHRONICITY 180, 181, 213 CICATRIZED GLANDS 211 CLASSIFICATION OF Empyema 231 Glands for surgical treatment 208 Glandular tuberculosis 70' . Lung abscess 231 Mixed infections 173 Pulmonary tuberculosis 110' Respiratory mixed infections 186 CLOSED GLANDS 70 COLD ABSCESS 156, 226 Examples of faulty treatment of 229-- Treatment of 227 Tryptic digestion in 226 COMBINED THERAPY 89, 155, 213, 217 COMPOSITION OF BISMUTH PASTE 218 CONCLUSION TREATMENT In bone and joint tuberculosis 91 In glandular tuberculosis 74 In lupus 141 In ocular tuberculosis .' 139 Of acute or active pulmonary tuberculosis 122 Of chronic pulmonary tuberculosis 118 Of incipient pulmonary tuberculosis 114 Of renal tuberculosis 103 254 INDEX CONCLUSION TREATMENT Con. PAGE Of tubercular peritonitis. 133 Of tuberculosis of the ear 139 With vaccines 179 CONDITIONS, SPECIAL 142 CONJUNCTIVAL TUBERCULIN TEST 35 CONSTITUTIONAL KEACTION 5, 39, 53, 56, 59, 61, 63, 80, 142 Appearance of sputum 20 Differentiation of 142 CONTAGIOUS DISEASES Contraindication to -test 25 Increased hypersusceptibility after 150, 151, 152 CONTAINERS For tuberculin dilutions 47 For vaccines . . . . '. 166 CONTRAINDICATIONS TO TUBERCULIN 21, 24 FOR TEST In contagious or infectious diseases 25 In epilepsy 25 In fever 25 In general miliary tuberculosis 25 In heart disease ". 24 In hemoptysis 26 In intestinal ulcerations 25 In nephritis 24 To conjunctival test 36 FOR TREATMENT In pulmonary tuberculosis 108 Of debility . 109 Of fever 108 COUGH, EFFECT OF TUBERCULIN ON 128 COUNTER OPENINGS FOR PROPER DIRECTION OF BISMUTH PASTE. . 223 COXITIS, TUBERCULAR (see Fig. 55) CULTURES FOR DIAGNOSIS 161 CUTANEOUS TUBERCULIN TEST OF VON PIRQTJET 28 Interpretations of 29 Negative findings in 30 Positive findings in 31 Traumatic reaction in 29 Variations in 30 DEBILITY 109 DEFORMITY, TREATMENT OF 89 DETERMINATION OF TUBERCULIN TEST 26 Army reports of 27 Binswanger's report of 27 DIAGNOSIS Animal inoculation for 162 INDEX 255 DIAGNOSIS Con. PAGE Cultures for 161 Difficulty of, in renal tuberculosis 98 Early, in renal tuberculosis 98, 99 Of infective organism 158 Physical signs in 162 Smear 159 Tuberculin reaction in 17, 20 Tuberculin, in renal tuberculosis 98, 99 DIETETICS 200 DIGESTION Effect of tuberculin on 127 Tryptie, in cold abscess 226 DILUENT 14 DILUTIONS OF TUBERCULIN 13, 14, 47 Containers for 47 Directions for making 14 Eeady made 16 Stability of 15 Tables of 15 DIRECTION or BISMUTH PASTE, PROPER Counter openings for 222 Roentgenography for 224 DOSAGE Effects of reaction on 55, 56, 59 Explanation of methods of 54 Of tuberculin in tests 20 Of Vaccine (see VACCINE DOSAGE) Principles in treatment 52, 53 Tables of (see TABLES) DRESSING FOR BISMUTH PASTE EETENTION 222 EAR TUBERCULOSIS 139 EFFECT OF TUBERCULIN As demonstrated by x-ray findings 130 On cough 128 On digestion 127 On expectoration 129 .On fever 128 On hemoptysis 129 On pain , . -. 127 On pathology 130 On physical signs 129 On pulse On symptoms 127 On temperature 128 On weight 127 256 INDEX PAGE EFFUSION, TREATMENT OF Peritoneal 137 Pleural 132 Purulent 231 EMPYEMA Bismuth paste in 233 Classification of 231 Olive oil in 233 Prevention of purulent reaccumulation 233 Stimulation of healing process in 233 Surgical treatment of 232 Treatment of 232 Vaccines for 232 EPILEPSY, CONTRAINDICATION TO TUBERCULIN TREATMENT 25 EQUIPMENT 42 ESCHERICH 's NEEDLE TRACT REACTION 32 EXPECTORATION, EFFECT OF TUBERCULIN TREATMENT ON 129 EYE TUBERCULOSIS 137 FEBRILE Pulmonary tuberculosis 112 Mixed infection 173 FEVER (see TEMPERATURE) FIBROUS PHTHISIS Ill FILTRATES, TUBERCULAR 8 FINDINGS (see NEGATIVE or POSITIVE FINDINGS) FISTULAS Combined treatment for 213, 217 Formation of 213, 217 Mixed infection in <. . . . . 213 FOCAL REACTION 19, 40 As an aid to vaccine treatment 179 FORMULAS For bismuth paste 219 For chemical method of softening cicatrized glands 212 FREQUENCY Of Bismuth paste injections 222 Of micturation in renal tuberculosis 99 GENERAL HYPERSUSCEPTIBILITY (see HYPERSUSCEPTIBILITY) GENERAL MILIAR Y TUBERCULOSIS 2,5 GENERAL PROPHYLAXIS 198 GENITO-URINARY TUBERCULOSIS (see RENAL TUBERCULOSIS) GLANDS Cicatrized 211 Closed 70 Open 71 Radical surgical treatment of 72, 74 INDEX 257 GLANDS Con. PAGE Soft 208 Suppurating 210 GANDULAR TUBERCULOSIS As primary infection 68 Beginning tuberculin treatment in 73 Best to acquire tuberculin technique in 66 Classification of 70 Closed glands 70 Open glands 71 Recurrent glands 71, 74, 83 Conclusion of tuberculin treatment in 74 General hypersusceptibility in 72 Eesults in 74 Surgical treatment of 208 Treatment of mixed infection in. . . 210 HEART DISEASE 24 HEMOPTYSIS 26 Contraindication to tuberculin test 26 Effect of tuberculin on 129 HEMORRHAGIC PULMONARY TUBERCULOSIS 112 HOECHST 's TUBERCULIN SERUM 7 HYGIENE, PERSONAL 200 HYGIENIC-DIETETIC-CLIMATIC TREATMENT IN PULMONARY TUBER- CULOSIS 107 HYPEREMIA Bier's 86, 88 Of focal reaction 19, 40, 179 HYPERSUSCEPTIBILITY 5, 19, 52 General, in glands 72 In bone and joint tuberculosis 90 Increased by radical operation 69, 72 Increased by contagious or infectious diseases. . . .25, 150, 151, 152 In pulmonary tuberculosis 112 In renal tuberculosis 101 Test for recurrence of 147 IDIOPATHIC PLEURISY 132 IMMUNE RESPONSE To tuberculin 4, 5, 6 IMMUNITY 1 Active Passive IMMUNIZATION, PROPHYLACTIC 78, 195 INCIPIENT Pulmonary tuberculosis HO Renal tuberculosis 97 17 258 INDEX PAGE INCUBATION. . 161 INDICATION FOR TUBERCULIN TESTS 18 INFECTIONS, MIXED (see MIXED INFECTIONS) INFECTIONS, ELIMINATION OF SOURCE OF 198 INFECTIOUS DISEASES ;. . . 25, 150, 151, 152 INJECTIONS OF BISMUTH PASTE 220 INOCULATION, ANIMAL 162 INSTRUCTIONS TO PATIENTS In proper dressing for bismuth retention 222 In taking of temperatures 48 INTERPRETATION ; | Of cutaneous tests 29 Of tuberculin tests 19 INTOLERANCE TO TUBERCULIN 144 INTERVALS Effects of reaction on 55, 59 In bismuth paste injections 222 In tuberculin treatment 55 In vaccine administration 174, 178 INTRACUTANEOUS TESTS 33 INTESTINAL ULCERATIONS 25 IRRITATIVE ACCUMULATIONS , In bone and joint tuberculosis 88 Serus 88 JOINT TUBERCULOSIS (see BONE AND JOINT TUBERCULOSIS) KIDNEY TUBERCULOSIS (see EENAL TUBERCULOSIS) LANDSMANN TUBERCULOL 10 LAPAROTOMY FOR TUBERCULAR PERITONITIS 133 LOCAL KEACTION 19, 39 LUNG ABSCESS Bismuth paste in 233 Classification of 231 Cumulations 232 Examples! of various forms of 235 Olive oil in treatment of 233 Prevention of purulent reaccumulations 233 Surgical treatment of 232 Treatment of 232 Vaccines in 232 LUNG TUBERCULOSIS (see PULMONARY TUBERCULOSIS) 66, 140 Beginning and conclusion treatment of 140 Local treatment of 140 Reactive method in 140 Tuberculin treatment of 140 INDEX 259 . PAGE LYSINS 4 MARAGLEANO 's SERUM 7 MARMOREK 's ANTI- TUBERCULOSIS SERUM 7 METHOD Of determination of opsonic index 4 Of making BE 9 Of making OT 8 OF TUBERCULIN TREATMENT i In lupus 140 Minute dose 51 Present day 52 Eeactive 51 MILIARY TUBERCULOSIS, GENERAL 25 MISCELLANEOUS TUBERCULAR CONDITIONS 132 MIXED INFECTIONS 157 Acute 173 Acute af ebrile 177 Acute febrile 173 Chronic 179 Classification of 173 Diagnosis of causative organism in 158 In bone and joint tuberculosis 213 In glandular tuberculosis 210 In lung abscess 231 In pulmonary tuberculosis (see RESPIRATORY MIXED INFECTIONS) In renal tuberculosis 101 Prophylactic immunization against 78, 195 Treatment of 173 MORO TUBERCULIN TEST 32 MULTIPLE MIXED INFECTION Treatment of singly or combined 181 NATURE OF TUBERCULIN T NEEDLES, HYPODERMIC 47 NEEDLE TRACT, EEACTION OF ESCHERICH 32 NEGATIVE FINDINGS IN CUTANEOUS TEST 30 NEGATIVE PHASE IN ACUTE MIXED INFECTION 178 NEPHRITIS 24 OCULAR TUBERCULOSIS 137 OLD or ALT TUBERCULIN 8 OLIVE OIL TREATMENT Of cold abscess 227 Of empyema 233 Of lung abscess 233 OPEN GLANDS 71 OPHTHALMIC REACTION 35 260 INDEX PAGE OPSONIC INDEX Methods of determination of 4 OPSONINS 3 ORTHOPEDIC APPLIANCES 154 ORTHOPEDIC TREATMENT 89 OT (OLD TUBERCULIN) 8 Method of making 8 To overcome hypersusceptibility to 12 PAIN, EFFECT OF TUBERCULIN ON 127 PASSIVE IMMUNITY 2 PASTE, BISMUTH (see BISMUTH PASTE) PATHOLOGY, EFFECT- OF TUBERCULIN ON 130 PERCUTANEOUS TUBERCULIN TEST OF MORO 32 PERITONITIS 133 Beginning and conclusion treatment in 137 Effusion in 137 Laparotomy for 133 Tuberculin treatment of 133 PERMANENT DAMAGE IN BENAL TUBERCULOSIS 97 PERSONAL HYGIENE 200 PHAGOCYTES 3 PHENOMINA OF TUBERCULIN EEACTION 18 PHYTHISIS (see PULMONARY TUBERCULOSIS) PHYSICAL SIGNS Effect of tuberculin on , 129 In diagnosis 162 PHYSIOLOGICAL ACTION OF TUBERCULIN . . . .- 53 PLEURISY Idiopathic 132 Tuberculin treatment of 132 POLYVALENT VACCINES 169 POSITIVE FINDINGS IN CUTANEOUS TEST 31 PRECIPITINS 4 PREJUDICE AGAINST TUREBCULIN, CAUSES OF 51, 66 PREPARATION Of tuberculins 7 Of vaccines 164 PRIMARY Mixed infections 188 Tubercular infections 68 PRINCIPLES UNDERLYING PHYSIOLOGICAL ACTION OF TUBERCULIN. . 53 PROGNOSIS IN PULMONARY TUBERCULOSIS 123 PROPHYLACTIC IMMUNIZATION 78, 195 Against acute exacerbations of mixed infection 197 Against epidemic infections 196 Against respiratory mixed infection 195 INDEX 261 PAGE PROPHYLAXIS, GENERAL, 198 PULMONARY ABSCESS (see LUNG ABSCESS) PULMONARY MIXED INFECTION (see RESPIRATORY MIXED INFECTION) PUL'MONARY TUBERCULOSIS 105 Contraindications to tuberculin treatment in 108 General hypersusceptibility in 112 Hygienic-dietetic-climatic treatment of 107 Prognosis and results in 123 Results of tuberculin treatment in 123 Statistics of 105, 126 Treatment 113 Beginning Of Acute 122 Of Chronic . 117 Of Incipient 114 Conclusion Of Acute 122 Of Chronic 118 Of Incipient ... 114 Tuberculin treatment of, in Germany 105 CLASSIFICATION OF 110 Acute or active Ill Afebrile 112 Calcareous Ill Chronic 110 Febrile 112 Fibrous Ill Hemorrhagic 11- Incipient 110 PULSE, EFFECT OF TUBERCULIN ON 128 PURULENT EFFUSION Prevention of reaccumulation 233 Treatment of 232 PYOGENIC RESPIRATORY MIXED INFECTIONS 184 RADICAL OPERATION As increasing general hypersusceptibility 69, 72 For tubercular adenitis 72, 74 In renal tuberculosis RADIOGRAPHY (see X-RAY) REACTION Constitutional (see CONSTITUTIONAL REACTION) Effect of dosage 55, 56, 59 Effect on intervals 55, 59 Focal 19, 4 . 17{) Local 19. Needle tract, of Escherich 32 262 INDEX REACTION Con. PAGE Of tuberculin in diagnosis 17 Ophthalmic or conjunctiva! 35 Phenomena of tuberculin 18 Traumatic, in cutaneous test 29 Tables showing _. 59 READY MADE TUBERCULIN DILUTIONS 16 RECORDS Of temperature 48 Of tuberculin treatment 43 RECURRENCE OF HYPERSUSCEPTIBILITY 147 RECURRENT TUBERCULAR GLANDS 73, 74, 83 RENAL TUBERCULOSIS ." 95 Beginning treatment in 103 Conclusion treatment in 103 Difficulty of diagnosis 98 Early diagnosis in 98, 99 Hypersusceptibility in 101 Incipient 97 Mixed infection in 101 Permanent damage from 97 Radical operation in 96 Source of infection of 95 Tuberculin in diagnosis of 98, 99 REPORT OF TUBERCULIN TESTS Army ! 27 Binswanger 27 RESPIRATORY MIXED INFECTION 184 Acute 192 Catarrhal 184 Chronic 186 Classification of ; 186 Primary 188 Prophylactic immunization against 195 Pyogenic 184 Secondary 187 Treatment of acute 193 Treatment of chronic 190 RESPONSE, IMMUNE 4, 5, 6 RESULTS OF TUBERCULIN TREATMENT In bone and joint tuberculosis 92 In glandular tuberculosis 74 In pulmonary tuberculosis 123 On individual symptoms 127 RETENTION OF BISMUTH PASTE 221 ROENTGENOGRAPHY (see X-RAY) SEE (SENSITIZED BE) 10 INDEX 265 PAGE SCALES, OFFICE 47 SENSITIZED BE (SEE) 10 SERUS ACCUMULATIONS 88 SINUSES (see FISTULAS) SKIN TUBERCULOSIS (see LUPUS) SMEAR FOR DIAGNOSIS 159 SOFT GLANDS 208 SOURCE OF INFECTION, ELIMINATION OF 198 SPECIAL CONDITIONS 142 Abscess formation 144 Autoinoculation 145 Constitutional reaction 142 Tri-monthly tests 147 Tuberculin intolerance 144 SPECIAL TREATMENT 153 SPUTUM During constitutional reaction 20 Tubercle bacilli in 20 STABILITY OF DILUTIONS 15 STANDARDIZATION OF VACCINE 164 STATISTICS 105, 126 STERIO X-EAT 224 STOCK VACCINES 168 Polyvalent 169 SUBCUTANEOUS TUBERCULIN TEST 37 Constitutional reaction in 39, 142 Focal reaction in 40 Local reaction in 39 Safety of 37 Serial method of dosage 22, 23 Symptoms of 39 Technique of 37 Treatment of 41 SUPPURATING GLANDS 210 SURGICAL TREATMENT Of empyema 232 Of lung abscess 232 Of tubercular glands 208 Eadical, in glands 72, 74 SYMPTOMS Of subcutaneous tuberculin test 39 Eesults of tuberculin treatment on individual 127 SYRINGE Bismuth paste 220 Tuberculin. . 14, 46 264 IHTDEX PAGE TABLES Of dilutions 15 Of dosage in tests 23, 24 Of dosage in treatment 57, 59, 60 Of dosage of BE 60 Of dosage of OT 57, 59 Showing reactions 59 TBk (TUBERCULIN BERANECK) 11 TECHNIQUE Acquiring of, for treatment 65 Of bismuth paste treatment 220 Of subcutaneous test 37 Of tuberculin administration 54 Of Von Pirquet test 28 TEIIPEKATUKE As a contraindication to tuberculin treatment in pulmonary tuberculosis 108 As a contraindication ta the tuberculin test 25 Curve in relation to time of vaccine administration 174 Differentiation of 142, 177 Effect of tuberculin treatment on 128 Influence on treatment 80 In pleurisy 133 Instruction to patients on proper taking of 48 Eeaction (see CONSTITUTIONAL REACTION) Records of 48 TOLERANCE Acquiring, by means of OT 12 Curve 61, 63 To toxic proteins in treatment 51, 65 TOXICITY Of vaccines 173 TESTS (see TUBERCULIN TESTS) THERAPY (see TREATMENT) TO (TUBERCULIN OBERS) 10 TOA (TUBERCULIN OBERS ALB) 8 TR (TUBERCULIN RESIDUE) 10 TRAUMATIC REACTION 29 TREATMENT Acquiring technique for tuberculin 65 Bismuth paste 86, 88, 220 Combined 89, 155, 213, 217 Effects of reactions on tuberculin 55, 56, 59 Intervals in (see INTERVALS) Method of dosage in tuberculin 52, 53, 140 Of autoinoculation 147 INDEX 265 TREATMENT Con. PAGE Of bone and joint tuberculosis (see BONE AND JOINT TUBER- CULOSIS) Of cold abscess 227 Of constitutional reaction 41 Of deformity gg Of effusion 231 Of empyema 232 Of glandular tuberculosis (see GLANDULAR TUBERCULOSIS) Of lung abscess 232 Of miscellaneous tubercular conditions 132 Of mixed infection 173 Of mixed infection in bone cavities and fistulas 213 Of pulmonary tuberculosis (see PULMONARY TUBERCULOSIS) Of renal tuberculosis (see EENAL TUBERCULOSIS) Of respiratory acute mixed infection 193 Of respiratory chronic mixed infection 190 Of tubercular glands (see GLANDULAR TUBERCULOSIS) Of tubercular peritonitis 133 Of tubercular pleurisy 132 Orthopedic 89 Principles involved in tuberculin 53 Proper record of 43 Results of tuberculin (see RESULTS) Special 153 Surgery in (see SURGICAL TREATMENT) Surgical (see SURGICAL TREATMENT) Tuberculin 51 Vaccine 173 X-ray in 224 TRYPTIC DIGESTION AS CAUSE OF SUPPURATION 226 TUBERCLE BACILLI During constitutional reaction 20 In sputum 20 TUBERCULAR Coxitis (see Fig. 55) Filtrates 8 Glands (see GLANDULAR TUBERCULOSIS) Peritonitis (see PERITONITIS) TUBERCULIN AF (Albumose-Free) 9 BE (Bacillary Emulsion) 9 Choice of 12 Containers 47 Contraindication to 21, 108 Dilutions 13, 14, 47 Immune response to 4, 5, 6 266 INDEX TUBERCULIN Con. PAGE In beginning treatment (see BEGINNING TREATMENT) In conclusion treatment (see CONCLUSION TREATMENT) In renal tuberculosis (see BENAL TUBERCULOSIS) In treatment (see TREATMENT) Intolerance to 144 Mixtures of 11 Nature of 7 Old or Alt 8 OT or T 8 Reaction in diagnosis 17 Results of, on symptoms 127 SEE (Sensitized BE) 10 Syringe 14, 46 TBk (Tuberculin Beraneck) 11 TO (Tuberculin Obers) 10 TOA (Tuberculin Obers Alt) 8 TE (Tuberculin Eesidue) 10 Tuberculol Landsmann 10 Tuberculose-Sero-Vakzin .10 Varieties of . 8 TUBERCULIN TESTS Army report of 27 Binswanger report of 27 Conjunetival 35 Contraindication to 21, 24 Cutaneous 28 Determination of ., 26 Dosage in 22 Escherich's needle tract in 32 Indications for 18 Interpretations of 19 Intracutaneous 33 Percutaneous, of Moro 32 Eepetition of 21 Subcutaneous 37 Treatment of 41 Tri-monthly 147 Von Pirquet 28 Variations in the cutaneous 30 TUBERCULOL LANDSMANN 10 TUBERCULOSIS General miliary 25 Of bones and joints (see BONE ANI> JOINT TUBERCULOSIS) Of glands (see GLANDULAR TUBERCULOSIS) Of the ear 139 Of the eye 137 INDEX 267 TUBERCULOSIS Con. PAGE Of the peritoneum (see PERITONITIS) Of the pleura 132 Of the skin '..... 140 Pulmonary (see PULMONARY TUBERCULOSIS) Renal (see RENAL TUBERCULOSIS) The three stages of gg Vicious cycle in g UROGENITAL TUBERCULOSIS (see RENAL TUBERCULOSIS) VACCINE 164 Autogenous 170, 215 Care of 168 Conclusion of, treatment 179 Containers f er 166 Polyvalent 169 Preparation of 164 Standardization 164 Stock 168 Time of, administration in relation to temperature curve. . . 174 Toxicity of 173 Treatment (see MIXED INFECTION) Use of singly 181 VACCINE DOSAGE In acute afebrile infection 177 In acute febrile infection 175 In acute respiratory mixed infection 193 In chronic mixed infection 181 In chronic respiratory mixed infection 190 In empyema 232 In lung abscess 232 In prophylactic immunization 195 VARIATIONS IN THE CUTANEOUS TUBERCULIN TEST 30 VARIETIES OF TUBERCULINS (see TUBERCULIN) Vicious CYCLE IN TUBERCULOSIS 6 VON PIRQUET TUBERCULIN TEST 28 WEIGHT, EFFECT OF TUBERCULIN ON 127 WOLFF-EISNER 's TEST 35 X-RAY FINDINGS For direction of bismuth paste 224 Showing effect of tuberculin 130 Sterio. . 224 University of California SOUTHERN REGIONAL LIBRARY FACILITY 405 Hilgard Avenue, Los Angeles, CA 90024-1388 Return this material to the library from which it was borrowed. 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