CoEege of ^IjpgicmniS anh ^urgeong THEODORE BERNARD SACHS, M.D. BORN AT DINABURG, RUSSIA, MAY 2, 1868 DIED APRIL 2, 1916, CHICAGO Sundry Lectures On the Medical Phases of Tuberculosis Delivered Before The Robert Koch Society for the Study of Tuberculosis FROM FEBRUARY 11, 1913 TO APRIL 20, 1916 PUBLISHED BY THE CHICAGO TUBERCULOSIS INSTITUTE MAY 1, 1916 ?'^ "R54 Digitized by the Internet Archive in 2010 with funding from Open Knowledge Commons http://www.archive.org/details/sundrylecturesonOOrobe PREFACE The first meeting of the Robert Koch Society for the Study of Tuberculosis was held on February 11, 1913, at the City Club, of Chi- cago. The organization was at that time known as the "Tuberculosis Study Circle of the Chicago Tuberculosis Institute." The Society was founded by Dr. Theodore B. Sachs, for the pur- poses which he outlined in the following reprint from the Journal of the American Medical Association, January 17, 1914: "A study of the existing anti-tuberculosis machinery in vari- ous cities discloses the absence of special physicians' associations for the study of the medical side of the problem. The lack of such associations that would bring together, at stated intervals, medical men interested in the disease for the purpose of discuss- ing its important phases seems to be a grave omission in the gen- eral scheme, considering the importance of the medical profession as a factor in the anti-tuberculosis movement, as well as the exist- ence of a large number of medical questions pertaining to tuberculosis on which the collective judgment of the profession can be formulated only through continuous discussion and study. "To meet this need all Chicago physicians connected with tuberculosis sanatoria, hospitals and dispensaries, as well as med- ical men interested in the study of the disease, were invited, under the auspices of the City Club, February 11, 1913, to attend the first meeting of the so-called 'Tuberculosis Study Circle.' "It was planned that the time between 12:15 and 1 o'clock be given to the luncheon, and the hour between one and two to the presentation of some important medical phase of tuberculosis, by someone who has made a thorough study of it. "The success of the first luncheon led to the others. The meetings have proved to be exceedingly popular, bringing to- gether for the first time, at regular intervals, physicians inter- ested in the study of tuberculosis, "(Signed) Theodore B. Sachs. "December, 1914." On January 8, 1914, the name of the Study Circle was changed to "The Robert Koch Society for the Study of Tuberculosis." A week later it was chartered, under that name, with the following organiza- tion: Charter members and Board of Directors : Group One — to serve one year: Dr. Henry B. Favill. Dr. Frank S. Johnson. Dr. Theodore B. Sachs. 4 PREFACE Group Two — to serve two years : Dr. Ethan A. Gray. Dr. John Ritter. Group Three — to serve three years: Dr. James Alexander Harvey. Dr. 0. W. McMiehael. President — Dr. Theodore B. Sachs. Vice-President — Dr. O. W. McMiehael. Secretary-Treasurer — ^Dr. John Ritter. At the meeting of October 18, 1915, Dr. Sachs stated that he was compelled, because of the large amount of work he had on hand, to relinquish the office of President of the Society. Dr. John Ritter, the present President, succeeded him in that capacity. The organization, in Chicago, of the "Robert Koch Society for the Study of Tuberculosis ' ' was conceived in the fertile brain of its founder, the late Dr. Theodore B. Sachs. From its very inception it was intended only as an auxiliary or affiliated society of the Chicago Tuberculosis Institute. The primary object of its creation was to supply to a community in need of definite and exact knowledge concerning that widespread dis- ease, tuberculosis, a readily accessible means for studying it in its en- tirety. Soon after its organization, through the instrumentality of the Executive Committee of the Chicago Tuberculosis Institute, a charter was asked for and granted by the State of Illinois, and the Society has ever since been subject to the laws governing the mother institution, the Chicago Tuberculosis Institute. The founder and his associates have always recognized this impor- tant fact, that to acquire definite knowledge in relation to this disease a most intensive study of the various subjects from different angles is necessary, and that the study must include all the medical aspects. With this object clearly crystallized in their minds, physicians, nurses, social workers and all such of the laity as were deeply interested in these topics were from time to time invited to attend these study hours. A very live interest in these study hours has been manifest from the very beginning, with a large attendance at each meeting. This little volume embraces a collection of the lectures given at the eighteen meetings, i. e., from February 11, 1913, to April 20, 1916. Unfortunately, only an abstract can be given in a few instances, be- PREFACE D cause no stenographic notes were made of those particular addresses. For the later ones we have had complete notes. The lectures are arranged in the order in which they were delivered, no attempt having been made at a systematic or progressive tabulation — because this collection is not intended to be a textbook nor a compen- dium on tuberculosis. Its purpose is that of a ready reference, as a companion for the busy tuberculosis worker who is in need of reliable information relative to special tuberculosis questions. It should always be borne in mind that this collection of papers on tuberculosis work in the present ranks of the present time, and is, as may be understood, subject to such slight changes as may be commen- surate with a better interpretation of many still obscure points. If the distribution of these papers should be the means of clearing up many obscure points and the reader conceives a better understand- ing of this important topic, enabling him to do better and more efficient work in the field of tuberculosis, to give greater comfort to those suf- fering from this disease, then the Robert Koch Society will feel that it has been well rewarded for its work. (Signed) John Ritter, M.D., President of the Robert Koch Society. Chicago, 111., May 1, 1916. To all the active tuberculosis workers of our country, to the physicians, the nurses, the social workers, to the various charitable beneficial organiza- tions associated in tuberculosis work, to the noble men and women who are ever ready with heart and hand to assist the unfortunate tuberculous, this col- lection of addresses on special tuberculosis topics is affectionately dedicated. CHICAGO TUBERCULOSIS INSTITUTE. TABLE OF CONTENTS MEETINGS OF THE EOBEET KOOH SOCIETY AND THE SUBJECTS DISCUSSED February, 11, 1913— "Ohemotherapy of Tuberculosis" 9 Prof. H. Gideon Wells, Director of Sprague Memorial Institute, University of Chieago. February 28, 1913 — "In What Class of Cases Should We Use Tuberculin, Par- ticularly in Dispensary Practice?" (Not included)* General Discussion. March 21, 1913 — "The Treatment of Pulmonary Tuberculosis With Artificial Pneumothorax" 13 Dr. W. A. Gekler, Associate Medical Director, Chicago Municipal Tubercu- losis Sanitarium. April 16, 1913 — "Some Phases of Immunity, With Special Eeference to Tuber- culosis." (Abstract) 21 Prof. Ludwig Hektoen, University of Chicago. June 16, 1913 — "Therapeutic Use of Tuberculin." (Abstract) 21 Dr. Charles L. Minor, Asheville, N. C. October 23, 1913 — "Pneumothorax in the Treatment of Tuberculosis" ... 23 Dr. John B. Murphy, Northwestern University Medical School, and Dr, Philip Kreuscher, Chicago. November 20, 1913— "The Present Status of Tuberculin Therapy" .... 27 Dr. Louis Hamman, Johns Hopkins University, Baltimore, Md. January 8, 1914 — "The Eelation of Bacterial Metabolism to Bacterial Infec- tion." (Not included)* Dr. Arthur I. Kendall, Professor of Bacteriology, Northwestern University Medical School, Chicago. March 26, 1914 — "X-Eay Diagnosis of Tuberculosis of the Lungs and Bronchial Glands." (Abstract) 34 Dr. HoUis E. Potter, St. Luke's Hospital, Chicago. Discussion by Dr. James T. Case, Battle Creek, Mich., and Dr. F. C. Turley, Chicago. April 9, 1914 — "Eelative Importance of Bovine and Human Sources of Infec- tion in the Production of Tuberculosis" 38 Dr. M. P. Eavenel, Professor of Bacteriology, University of Missouri, Co- lumbia, Mo. June 19, 1914 — "Present Status of Immunization Against Tuberculosis" . . 45 Dr. Gerald B. Webb, Consulting Physician Cragmor Sanatorium and Sun- nyrest Sanatorium, Colorado Springs, Colo. July 16, 1914 — "Etiology and Morbid Anatomy of Bone and Joint Tubercu- losis" 50 Dr. Charles M. Jacobs, University of Chieago. "Non-Operative Treatment of Tuberculosis of Bones and Joints" ... 54 Dr. John L. Porter, University of Chicago. "Surgical Treatment of Tuberculosis of Bones and Joints" 57 Dr. Edwin W. Eyerson, Eush Medical College Discussion: Dr. John Eidlon, Northwestern University Medical School. * No stenographic report made. 7 8 TABLE OF CONTENTS September 16, 1914 — "Non-Tuberculous Lesions Occurring in Tuberculosis" . 60 Dr. Joseph Zeisler, Northwestern University Medical School. "Tuberculous Lesions" 62 Dr. Oliver S. Ormsby, Eush Medical College. "Treatment of Cutaneous Tuberculosis" 65 Dr. William A. Pusey, University of Illinois. Discussion: Dr. Theodore B. Sachs, Dr. Joseph Zeisler. October 29, 1914 — "The Larynx in the Early Stages of Pulmonary Tubercu- losis" 69 Dr. Elmer L. Kenyon, Eush Medical College. "Symptoms and Diagnosis of Laryngeal Tuberculosis" 72 Dr. E. Fletcher Ingals, Eush Medical College. "Prognosis and Treatment of Laryngeal Tuberculosis" 76 Dr. Norval H. Pierce, University of Illinois. "Prognosis and Treatment in Laryngeal Tuberculosis" 79 Dr. G. A. Torrison, Eush Medical College. March 25, 1915 — "Pregnancy and Tuberculosis" 81 Dr. Charles S. Bacon, University of Illinois. "Pregnancy and Tuberculosis" 86 Dr. Joseph DeLee, Northwestern University Medical School. October 18, 1915 — "Clinical Symptoms and Physical Signs in Early Diagnosis of Tuberculosis" 92 Dr. F. M. Pottenger, Medical Director of Pottenger Sanatorium, Monrovia, California. Jainuary 19, 1916 — "Complement Fixation in Tuberculosis" 103 Dr. H. J. Corper, Municipal Tuberculosis Sanitarium, Chicago. February 17, 1916 — "Tuberculosis of the Kidney" 112 Dr. Herman L. Kretschmer, Eush Medical College. March 17, 1916 — "The Specific Eoentgen Markings Characteristic of Pulmonary Tuberculosis" 120 Dr. Kennon Dunham, University of Cincinnati. 11 20, 1916 — "The Lymphatics and Lymph Eelation to Disease Processes" . Dr. W. S. Miller, University of Wisconsin. April 20, 1916 — "The Lymphatics and Lymphoid Tissue of the Lung and Their Eelation to Disease Processes" 123 THE CHEMOTHERAPY OF TUBERCULOSIS By H. Gideon Wells, M.D. CHICAGO The principles of chemotherapy, as laid down by Ehrlich, are of so fundamental a character that there is no limit to their application in infectious diseases, and possibly in cancer. With the spirilloses and trypanosome infections in which most of the work has so far been done, the conditions are favorable for the meeting of the drug and the germ, since in most forms of these diseases the germ lives chiefly in the blood. It is noteworthy that the only disease in which therapia magna sterili- sans has been practiced successfully on an empirical basis is also a blood infection, malaria. The consideration of tuberculosis from the standpoint of chemotherapy brings in distinctly new problems owing to the fact that the bacteria are largely located in points specifically removed from the circulation by proliferating tissues. This avascularity must of necessity have a large influence on the meeting of the drug and the germ, and this has perhaps been responsible for the lack of success of innumerable empirical attempts at chemotherapy which have been made with this disease in the past. Avascularity of an infected tissue may make for either assistance or hindrance in chemotherapy, for we can imagine that the drug may accumulate in the avascular area, just as, for instance, calcium salts do, or, entering avascular and vascular tissue alike, it might remain longer where there is no circulation. Certain drugs may be either destroyed or activated by living cells, and hence have either a greater or less effect in necrotic portions of the tubercle than elsewhere in the body. To attack the problem of tuberculosis chemotherapy it seems necessary to learn first just to what extent dif- ferent classes of chemicals enter tubercles, both early and advanced, how much they tend to accumulate specifically in tissues and how long they remain there. For a chemical which is to destroy the tubercle bacillus, it would seem, should be one that will enter readily avascular tuberculous lesions, and, if possible, enter or accumulate in such tissues more than in normal tissues. The problem is further complicated by the chemical composition of the tubercle bacillus, with its resistant fatty and waxy material, which must make its permeation and destruction a very different matter from the attack of the other naked and delicate trjT)anosomes, spirillae and spirochaetes. In the investigation of the subject, the fatty matter of the tubercle baciUus, while perhaps an obstacle to chemotherapy, makes attacks of the problem appear easier, since the permeability of the bacteria would seem largely determined by this substance, which can be extracted from them in large amounts and rendered available for experimental work in vitro, without at the beginning calling for exten- sive animal experimentation. The influence of the fatty constituent of 10 THE CHEMOTHERAPY OP TUBERCULOSIS the cells upon the permeability of tissue cells to drugs and dyes has already been extensively investigated, and we have many clues for investigation of the permeability of the B. tuberculosis. We have found it possible to attack directly some of the problems involved, while others have called for preliminary studies of certain fundamental questions. A study of the permeability of tuberculous lesions demonstrated that they behave like simple colloids in this respect, permitting crystalloids to diffuse readily through them, but being little, if at all, permeable to certain large coUoidal molecules. These facts were determined in the following way : Guinea pigs and rabbits with tuberculous lesions were injected with various iodine compounds, and after varying periods the animals were bled to death and the blood and tissues analyzed for iodine. The blood practically always contains more iodine than any tissue or organ, whether normal or tuberculous. The liver usually contains about one-third as much iodine per gram as the blood, the spleen about the same as the liver, the lungs a little less, the muscle about one-eighth to one-tenth as much as the blood. The kidney, how- ever, as a rule, has as large a proportion as the blood, and more during active secretion. The effects of pathological changes upon the tissues were very definite. Tuberculous lymph-glands, as 0. Loeb first showed, take up relatively more iodine from the blood than do the liver, spleen, and the lungs of the same animal. When the caseous material was abundant enough to permit of separation from the rest of the gland, it contained much more iodine than did the non-caseous portion of the gland, as is seen in Experiments 4, 5, and 14 : No. 4 No. 5 No. 14 Gland substance 0.295 0.285 0.007 Caseous contents 0.481 0.790 0.013 Tuberculous lesions in the eye show, as was also found by Loeb and Michaud in four experiments, an increased capacity for taking up iodine. That the entrance of iodine into tuberculous tissues is not characteristic of tuberculosis is established by analysis of tissues of animals in which necrosis and exudates were experimentally produced. Of all the tissues, the normal kidney alone seems to be so permeable for iodine that it comes to contain the same proportion as the blood. If we take muscle which is not normally so permeable to iodine, we find the interesting fact that necrotic areas in it also tend to contain approximately as much iodine as the blood. The explanation of these results must be as follows : The partial impermeability of living cells is destroyed when the cell is killed. Therefore, the readily diffusible iodine compounds pres- ent in the blood and tissue fluids will diffuse into necrotic tissue elements just as they would diffuse into any inert water-filled colloidal mass, with resulting tendency to approach osmotic equilibrium of iodine in the blood and necrotic tissue. That it does not depend upon chemical attrac- tion or even a specific physical absorption is shown by the fact that H. GIDEON WELLS, M.D. 11 if some time is allowed for the iodine to be excreted in part from the body, it leaves the necrotic tissues, the blood and the normal tissues pari passu. There is nearly always somewhat less iodine in inflammatory exudates than in the blood. The presence of iodine in exudates would seem also to be dependent entirely upon simple diffusion. The high iodine content in the tuberculous eye is presumably to be explained as due in part to the inflammatory exudate present and probably in less degree to necrotic tuberculous tissue. Similarly, compression atelectasis of the lung, produced by pleural exudates and resulting in edema and inflammatory exudate in the alveoli, is associated with slight iodine increase in the injured lung. This would seem to explain the observa- tions of Bondi, Jacoby, Fillipi, Nesti and Loeb, that drugs tend to enter inflammatory exudates. Therefore we are led to the conclusion that the supposed affinity of certain drugs for certain pathological tissues merely depends on a decrease in the normal impermeability of diseased cells or diffusion into exudates in the diseased area, or both. Necrotic tissues, whether tubercles or other lesions, behave like any non-living colloidal mass into which crystalloids diffuse readily and rapidly, while colloids enter very slowly or not at all. Possibly bacteri- cidal substances may be found, which, like calcium, will tend to accumu- late in tuberculous areas. The behavior of the tubercle bacilli them- selves to fat-soluble dyes has been studied by Hope Sherman. There is a little literature on staining of bacteria by fat dyes, and a prevalent belief that acid-fastness depends largely or solely on the wax of the acid-fast bacteria. Miss Sherman investigated the behavior of many fat-soluble and fat-insoluble dyes, and found that in cultures of tubercle bacilli there is a considerable amount of fatty material free between the bacteria which readily stains with fat-soluble dyes, but the dyes do not stain the bacilli readily, if at all. On the other hand, many dyes which are insoluble in fats, as fuchsin, methylene blue and eosin, stain the bacilli readily and intensely. This determines that the chief factor is not the fatty content as commonly believed. Miss Sherman found that simply crushing bacilli between cover-slip and slide deprives them of their acid-fastness and also makes them permeable to fat-soluble dyes. Evidently fat-solubility is not a necessary quality in a substance which is to penetrate the tubercle or the bacillus, but apparently quite the opposite. The fact that water-soluble dyes can penetrate the tubercle bacillus adds much interest to investigations of vital staining of tuberculous lesions. Goldmann, 1909, reported an exhaustive investigation of the effect on the tissues of the normal body of the groups of vital stains, including trypan-red, and trypan-blue already studied by Ehrlich and his co-workers, comparing these with isamine-blue and pyrrol-blue which act in a similar way. These workers, however, have not taken up the study of the ehemotherapeutic value of vital stains in tuberculosis, although Goldmann studied the behavior of tubercles in animals injected 12 THE CHEMOTHERAPY OF TUBERCULOSIS with these dyes. Recently a series of papers has appeared dealing with the so-called Finkler's Heilverfahren, from the laboratory of the Grafin von Linden. This method uses either methylene-blue (chloride of iodine) or copper compounds, or both. More or less favorable results were reported in the few experimental animals tested, and also in a number of tuberculous patients. Dr. Lydia M. De Witt has investigated these dyes in my laboratory. She found a considerable number of dyes which penetrate the tubercles readily and are well borne by the animals ; some dyes also penetrate the tubercle bacillus in the lesions and some have bactericidal power on these bacilli in vitro. De Witt did not find any definite curative effects from any of these or other dyes in infected tuberculous guinea-pigs. A rather spectacular series of papers has appeared by von Linden, Meissen and Strauss, stating that copper salts of various sorts have a striking therapeutic effect upon tuberculosis, both of men and experi- mental animals. Our animal experimentations are totally in disagree- ment with the above results. Pekanowich, who attempted to use the von Linden methods in patients with pulmonary tuberculosis, and his colleague Somagyi, treated skin tuberculosis with copper compounds, and observed no favorable effects. In closing, a review of recent studies of gold in the chemotherapy of tuberculosis is warranted by their highly interesting character. These, reported by Feldt, are based on two observations, one made years ago by Koch that gold salts have a remarkable bactericidal effect on tubercle bacilli. This has been corroborated by Bruck and Glueck, who obtained decided therapeutic effects by repeatedly injecting gold and potassium cyanide intravenously into patients with lupus. Feldt found gold salts effective in dilutions of 1 :100,000 up to 1 :2,000,000, as con- trasted to copper salts which he found ''on the border of inactivity." The other basic observation is ascribed to Liebreich, and is the property of cantharidin to cause severe reactions in any inflammatory focus. This suggested to Spiess that cantharidin might be used as a vehicle to gold in tuberculous lesions, and experiments performed along this line gave encouraging result. Further investigations with gold can- tharidin preparations will be awaited with much interest. THE TREATMENT OF PULMONARY TUBERCULOSIS WITH ARTIFICIAL PNEUMOTHORAX By W. a. Gekler, M.D. CHICAGO Over one hiindred years ago Itard, of Paris, first investigated the causes of natural pneumotliorax. Some of the symptoms and signs of this condition had been known since the time of Hippocrates, but it remained for Itard to give the first clear description of a number of cases in which fluid and air together occurred in the thorax during the course of pulmonary disease. Pneumothorax had been known several centuries before Itard 's time, usually as a complication of stab wounds of the chest. Itard was the first to associate this condition with pul- monary disease. Laennec gave us a good description of the physical signs and symptoms of natural pneumothorax. The occurrence of a spontaneous pneumothorax has long been looked upon as a practically fatal complication of an existing tuberculosis. We know that many consumptives die within a few hours or days after the occurrence of an acute pneumothorax, as a rule, suffocation being the cause of death. "Within recent years, however, more and more observers have been reporting cases of spontaneous tuberculous pneumo- thorax, where the condition was recognized promptly and treated con- servatively, resulting in a cure. The sudden cessation of sputum and fever in these favorable cases, along with the improvement in the gen- eral condition and strength, led to the advocacy of the artificial pneumo- thorax as a means of treatment of tuberculosis of the lungs. Carson, an English physician, was the first, so far as we know, to suggest this mode of treatment (1821). Independently of him Spaeth, a German physician, made the same suggestion in about 1870. It remained for Forlanini, of Pavia, to first put this method into actual practice. He published his results at the International Tubercu- losis Congress in Eome, 1894. Murphy, of Chicago, independently of Forlanini, reported his results in a number of cases in the American Medical Journal of 1898. Lemke, in 1899, published a preliminary report of fifty-three cases treated by him, in The Journal of the Amer- ican Medical Association, and at about the same time ScheU published his report in the New York Medical Journal. For several years after Murphy and Lemke reported their work, the procedure apparently fell into disuse in this country. In the last four or five years it has been taken up by a large number of men in different parts of the country, and seems to be again gaining a firm foothold in all sections of the country. In 1904, Brauer, of Marburg, Germany, began his investigations of artificial pneumothorax, and to him more than anyone else we owe our exact knowledge of this subject. He, with his experimental work and 14 ARTIFICIAL PNEUMOTHORAX his investigations of those cases which came to autopsy, worked out the details of this method and put what had been up to this time an empirical procedure on a rational basis. It is to him that we owe the modern lung collapse therapy of tuberculosis. "While it is true that these methods are only applicable in a limited number of cases, yet, as he himself says, these cases in which we achieve success are a net gain in our treatment of a disease which is one of the most difficult problems with which we have to contend. Every life saved by the collapse treat- ment is one which would otherwise be lost, and this more than justifies us in making use of this treatment wherever it is indicated. In producing an artificial pneumothorax we have two methods to choose from, that of Forlandni and that of Brauer. Forlanini simply introduces a needle connected with a gas container and a manometer into the chest, relying on the fluctuations of the manometer to indicate when he has the point of his needle between the two pleurae. The dis- advantage of the simple puncture is that one cannot always tell with certainty that the point of the needle has not penetrated into the lung. One must of necessity work in the dark, so to speak, and this is not without risk to the patient. There have been a number of cases in which sudden death from air embolus has occurred as a result of gas being injected into one of the pulmonary veins. One must not forget that there is normally no pleural cavity. The visceral and costal pleurae are in close apposition, with only a very thin layer of fluid between them, which acts as a lubricant. The exceeding thinness of the two layers of pleura is reason enough why a simple puncture as Forlanini uses can result in injury to the lung, as well as sudden death. I had occasion, while working in the City Hospital of Frankfort, Germany, to observe a case which came to autopsy, and in which an attempt had been made to produce artificial pneumothorax by Forlanini 's method. There was an encapsulated empyema about the size of a goose egg at the point where the puncture had been made, and this had undoubtedly been caused by the puncture of a tuberculous focus of no small size on the surface of the lung. When the needle penetrates the lung, and is at the same time fixed by the thoracic wall through which it has been thrust, every respiratory movement must result in tearing of the lung tissue. "We have similar experiences in puncturing the spleen. When the lung is consolidated at the point where the puncture is made, the veins are kept dilated by the consolidated tissue surrounding them, and they cannot be pushed aside by the needle as would possibly be the case in healthy lung tissue. These two facts make the occurrence of an air embolus easy. The advantage of this method of Forlanini 's lies in its simplicity and ease, and it is undoubtedly much more agreeable to the patient. Brauer 's method consists in laying bare the costal pleura at a point where one may be fairly certain not to strike adhesions, which is usually in the fifth or sixth interspace in the axillary region. An incision from W. A. GEKLER, M.D. 15 one and one-half to two inches long is quite sufficient, and the opera- tion can be carried out under local anesthesia. This method, while not at all difficult for one who has even slight skill in surgery, entails the strictest asepsis and the same attention to details as a major operation. It must not be forgotten that a large body cavity is being opened, and infection may have very serious consequences. The patient, as a rule, receives a hypodermic injection of a quarter grain of morphin fifteen or twenty minutes before the operation. I use a one-half of one per cent solution of novocain for anesthesia, and thor- oughly infiltrate the skin of the area where the incision is made. After incising the skin and superficial fascia, all bleeding vessels are clamped off so that the field of operation is as nearly absolutely dry as possible. The blunt dissection of the intercostal muscles is often painful, but is quickly accomplished. When the costal pleura has been laid bare, one can see the mottled lung beneath, gliding backward and forward with every respiratory movement. A very slight pressure with the blunt cannula causes a rupture of the costal pleura, and one can hear the air entering the pleura with a hissing sound. The cannula is then tightly packed about with damp sponges to keep any gas from escaping, and before attaching the rubber tube from the gas bottle, I pass a thin ureter catheter through the cannula as a probe to give some indication as to whether the lung has retracted or not. The gas apparatus consists of two three-liter bottles, graduated at every fifty and one hundred c.c, connected at the bottom with about two feet of rubber tube, one of the bottles being filled with nitrogen gas and one with a solution of bichloride of mercury. The sublimate solution flowing into the other bottle displaces the gas and forces it out through the tubing and cannula into the pleural cavity. Between the cannula and the gas bottle I connect, by means of a three-way cock, a small mercury manometer, which gives me the pressure under which the gas flows into the thorax, and, when the flow of gas is stopped, the pressure I have in the pneumothorax. At the first sitting I never inject more than five or six hundred c.c. of gas. In closing the wound, care must be taken that the intercostal muscles are tightly sutured, so as to prevent the occurrence of subcu- taneous emphysema, which, while annoying, is not dangerous and usually subsides within a week. Five or six small skin sutures are sufficient to close the wound, which is then dressed in the ordinary manner, with no drains. "With good asepsis and first-class suture material, there is no danger of wound infection and subsequent empyema. The object of this operation is simply to produce a small bubble of gas which can, at later punctures, be enlarged. I usually puncture the first time two or three days after the operation. The equipment is practically the same as at the first operation, with the exception that the sharp needle is substituted for the blunt-pointed cannula. It is hardly necessary to say that one does not puncture through the wound 16 ARTIFICIAL PNEUMOTHORAX made at the first operation, but in one of the interspaces near it. Of course, I always make an X-ray examination to determine exactly the size and location of my pneumothorax before puncturing. In this way I avoid striking possible adhesions with my needle, and also avoid injur- ing the lung by puncturing too deeply. After the first puncture, I punc- ture every week, until I notice by the amount of gas necessary at each injection that resorption is taking place more slowly, and then the intervals between punctures are lengthened until, in several months, patients go two or three weeks without further punctures being necessary. It is best to keep the pneumothorax at such a pressure that there are no respiratory movements of the collapsed lung, which is usually a pressure of -j-3 to -|-10 mm. of mercury on expiration, and from to +1 or +2 mm. on inspiration. These pressures vary in the individual cases with the elasticity of the mediastinum and the degree of collapse obtained. The production of an artificial pneumothorax cannot be said to be an operation requiring an extraordinary amount of skill, and the same can be said of the subsequent injections of gas. The difficulty with this mode of treatment lies in the selection of cases. On this one point alone one finds great diversity of opinion. From the accounts in the medical literature, and from my own experience, I have found that the more rigidly one adheres to Brauer's precepts the greater is the success attained. Operative interference should be reserved for those cases in which the usual sanatorium treatment does not bring success. Strictly incipient cases should, of course, not be treated sur- gically. A proportion of the moderately advanced cases will also respond readily to non-surgical treatment. We have, however, a number of advanced and far advanced cases in which the disease seems to show no inclination to heal, in spite of anything one can do. Cavities of any appreciable size very seldom can be made to heal without surgical inter- ference. In these cases, where the active disease is limited to one side, one is justified in attempting the pneumothorax treatment. Laryngeal tuberculosis is not a contra-indication. "Where there are active lesions in both lungs, artificial pneumothorax on one side is very apt to cause the disease to progress more rapidly on the other. Tuberculosis of the bowels or peritoneum is an absolute contra-indication to operative interference with the disease of the lung. Tuberculosis of the kidneys and generalized tuberculosis are also contra- indications. Laryngeal tuberculosis, with great destruction of laryn- geal tissues, makes artificial pneumothorax inadvisable. The greatest possible accuracy in physical and X-ray examinations is necessary for the proper selection of the eases. Very careful percussion will almost always give us approximately the extent of any consoli- dations. It is in auscultation that we encounter difficulties in the advanced and far advanced cases. With changes in the breath sounds and rales transmitted from one side to the other and transmitted from W. A. GEKLER^ M.D, 17 one place on one side over the remainder of that side, it is no wonder that the examiner is occasionally confused. Usually repeated exam- inations are necessary to arrive at a conclusion. The greatest difficulty lies in the diagnosis of pleuritic adhesions. In some cases, where there is a history of a previous pleurisy, and where, on physical and X-ray examination, there is very little, if any, opening up of the comple- mentary space, one is occasionally surprised to find at operation few or no adhesions. In other cases, where careful physical and X-ray exam- inations do not reveal any evidences of pleuritic adhesions, it may, at operation, be absolutely impossible to inject any gas between the pleura. Sometimes, after exposing the costal pleura, the lung may be seen glid- ing back and forth beneath, and yet small, thread-like adhesions may exist in sufficient number to hinder a coUapse of the lung. The examination with the X-ray is fuUy as important as the physical examination. As a rule, I make one large plate of the entire chest and a smaller one of only the apices. In addition to this, the examination with the fluorescent screen shows the movability of the diaphragm, and has the advantage over the plates in that one can turn the patient in any position one wishes, and often get a more accurate idea of the exact location of larger consolidations and cavities. The plates show much greater detail and bring out things that cannot be detected with the screen. They are, of course, a permanent record, and can be examined and studied with more thoroughness than a screen examination of a patient would allow. It would obviously be impossible to keep a patient before an X-ray tube for ten or fifteen minutes, on account of the danger of X-ray burns, and on account of the fact that no X-ray tube will stand more than a minute or two of operation at a time, with any con- siderable current going through it. Both screen and plate examinations are absolutely indispensable. We have no other means of locating deep seated lesions, although, of course, one cannot determine by the X-ray examination whether or not these lesions are active. A considerable amount of healed trouble on the supposedly well side, as indicated with the X-ray, would be a contra-indication to operative interference. It is essential that the operator have equal skill in X-ray as well as physical diagnosis, because neither one is as serviceable as the two in conjunction. In nearly every case the results with one method will supplement and complete those obtained with the other. Here I wish to state that it is only by having frequent autopsies to check our diagnoses that we can obtain the necessary accuracy. The findings at the autopsy table will, more than any other one thing, teach us to be modest in our estimation of our own skill, and correct habitual mis- takes in diagnosis. The result of the operation depends directly upon the degree of collapse of the lung one can produce. Where numerous adhesions will not permit the larger part of the lung to collapse, there is little or no change in any of the patient's symptoms. Where an extensive collapse is produced the patient usually notices a more or less marked diminution 18 ARTIFICIAL PNEUMOTHORAX in the cough immediately following the operation. Usually there is an increase in the amount of sputum the next day, to be followed from that time on by a marked decrease. One occasionally notices the same thing after the first few punctures. Sometimes there is also an increase in the fever immediately following the operation, due, no doubt, to the toxins forced out of the lesion by the compression. More often one notices an immediate drop in the temperature, and, where one has secured a good collapse of the lung, the fever will often entirely dis- appear within a few days. Quite often, where there is an increase in the fever, any healed lesions that may be present will show signs of irri- tation, which disappear in the course of several days, just as in a con- stitutional tuberculin reaction. When the patients become free of fever and the cough and sputum are reduced, there naturally results a marked change for the better in the general condition. The appetite improves and with it the strength. Patients do not always gain so rapidly in weight as one might expect, but they usually gain slowly and steadily. In several weeks they are usually able to be up and about without any noticeable bad effect on the condition of the lung or on the general condition. These patients do not notice any dyspnea on ordinary exertion as one might perhaps expect. Circulatory disturbances are also uncommon. There is no noticeable hypertrophy of the right heart. Several of these operative cases have come to autopsy and were reported by Graetz. One is struck by the amount of connective tissue formation in the lung, as compared with other tuberculous cases in whom there has been no operative inter- ference. In tuberculous lesions, as in other lesions, healing means suf- ficient formation of scar tissue to replace the defect. In tuberculous cases treated by other methods, including various kinds of tuberculin and vaccines, I have never seen such marked connective tissue growth in affected lungs as in these operative cases. Nor does one, in ordinary cases, see these broad, flat scars indicating healed cavities. Here, again, the autopsy table furnishes the final proof of the value of a method of treatment. Why does the collapse of a tuberculous lung bring about such marked changes in the condition of a patient 1 We know that the flow of lymph from the lungs to the bronchial glands, and into the general circula- tion, is, to an extent, controlled by the respiratory movements of the lung. Where the chest wall is elastic and the diaphragm unhampered in its movements, there is possible the greatest amount of respiratory expansion and contraction of the lung, with a corresponding rapidity in the flow of lymph. In any normal lung, the flow of lymph from the parenchyma to the hilus is greatest in those parts where the respiratory movements are greatest. In the tuberculous lungs, the toxins are borne from the lesion into the general circulation in the lymphatic fluid, and the more rapid the flow of lymph, the more toxins brought into the general circulation, and the more severe are the symptoms of this intox- ication. W. A. GEKLEB, M.D. 19 In the ordinary sanatorium treatment of tuberculosis, we try to reduce to a minimum this absorption of toxins, by putting the patient at as nearly absolute rest as possible, thus reducing the amount of movement of the lungs. In inducing collapse of the lungs we go farther still, in that we almost entirely stop the lymphatic flow by preventing any respiratory movements. There results in the collapsed lung, not a hyperemia and stasis, as one might at first expect, but an anemia, and with it, of course, a diminution in the amount of the lymphatic fluid in the collapsed organ. In other words, we prevent the toxins from getting into the general circulation, and causing the toxic symptoms which are common to this disease. This explains the cessation of fever, improvement in the appetite, and disappearance of such other symptoms as may be caused by this intoxication, as, for instance, disturbances in digestion. As remarked before, it is very difficult, with any of the means we now have at our command, to bring about healing of a cavity that has attained any considerable size. By compressing the lung, we can often bring the walls of the cavity in apposition, and thus bring about complete and permanent healing. This explains the great decrease in the amount of sputum and, of course, with it the cough in these cases. Not only that, but we prevent mechanically those movements of the tissue which hinder formation of sear tissue. Just as we often put tuberculous joints in plaster casts to prevent movement and permit a scar to be formed, so do we put the lung in a cast of gas, with the same end in view. The question at once arises, — will these cases really stay cured, or will the disease continue to make progress, when the lung is allowed to expand again? I can only relate what I myself have seen, and say that in those cases where a satisfactory collapse was obtained, the per- manent results, even in advanced and far advanced cases, are often as good as those we obtain with incipient cases treated by non-surgical methods, — in other words, clinical cure. I have known women patients to get married, after having gotten weU from tuberculosis with pneu- mothorax treatment, and even go safely through the ordeal of child- birth, which it seems to me is as good a test as any we have. During my year and a half as Brauer's assistant, I had opportunity to see and examine practically all of his cases who reported for re-examination and observation, and most of them were engaged in their usual avocations, only observing such precautions as any intelligent person would observe who was familiar, from personal experience, with a disease as treacher- ous as tuberculosis. One of these cured cases was an orderly in Brauer's clinic, and did quite as heavy manual labor as was exacted of other orderlies who had never been sick. It seems to me that these results speak for themselves. As a rule, we flnd adhesions sufficient to prevent satisfactory col- lapse of the lungs in about 25 per cent, of the cases on whom we attempt 20 ARTIFICIAL PNEUMOTHORAX to operate. These patients, realizing the hopelessness of their condition, often ask us to do something for them, even to the extent of submitting them to a dangerous operation. In these eases we can often induce sat- isfactory collapse of the lung by some form of thoracoplastic operation. The thoracoplastic operations for producing collapse of the lung in cases of tuberculosis were first advocated by Brauer, although a number of surgeons had made attempts to treat cavities and tuberculous abscesses of the lung surgically long before his time. This is not the place to go into details concerning this work, but I just wish to state that I have seen cases in which sufficiently satisfactory collapse was produced by such an operation to result in healing of the diseased lung. Among the patients at the Indiana State Hospital for Tuberculosis, I have made eleven attempts to induce artificial pneumothorax. In two cases it was absolutely impossible to get any gas into the chest, on account of very extensive adhesions. In another case, it was possible to get a small amount of gas into the pleural space, but on attempting to enlarge this small pneumothorax, which was on the left side, there resulted circulatory disturbances, which made it impossible to continue this form of treatment. None of these patients were permanently injured by these attempts. In five other cases, a partial collapse was secured, sufficient to result in more or less benefit to the patients, as evidenced in decrease of fever, cough and sputum, and betterment of the general condition. I doubt, however, as to whether it will be possible to bring about heal- ing in all of these five cases. The symptomatic improvement has, so the patients feel, more than repaid them for having submitted to the operation. In three cases, I have been able to get a degree of collapse which, I believe, by the progress we have made up until this time, will result in clinical cures. In only one of these eleven cases were there no adhesions whatever, and a perfect collapse was possible. In Brauer 's cases, there were about 40 per cent, successes, a result which is all the more wonderful when one considers that he, up until a year or so ago, would only consent to operate on the absolutely hopeless cases. He now takes the stand that it is often wise to operate on patients who are not so advanced as those whom he has reported, and he believes that a still better record can be achieved. We have, then, another weapon to use in our fight against tuber- culosis, and while its use must of necessity be limited, it nevertheless can be employed in saving lives that are now hopelessly lost. The col- lapse therapy, whether it be by means of artificial pneumothorax or some plastic operation, is entirely rational, and supported by clinical and experimental evidence. It has won recognition, both in this country and abroad, and can no longer be ignored. The results of this work and the principles underlying it also go to prove that there is an entirely mechanical factor in the growth of a tuberculosis process, and that this factor, as well as the theories of immunity, must be considered in attempting to explain consumption of the lungs. SOME PHASES OF IMMUNITY WITH SPECIAL REFERENCE TO TUBERCULOSIS* By Ludwig Hektoen, M.D. university of chicago The functions of antibodies in immunity were discussed and the facts known in respect to the formation of antibodies under natural and experimental conditions were presented briefly. Then the antigenic properties of the tubercle bacillus and the mechanisms by which the body protects itself from tuberculosis and resists tuberculous infection once established were considered. Finally the treatment of tuberculosis and mixed infection in tuberculosis by means of various kinds of vac- cines (including tuberculins) was discussed. The importance of auto- genous vaccines was emphasized and the efforts of manufacturers to stampede the medical profession into the indiscriminate use of com- mercial vaccines of various kinds, stock and polyvalent, strongly con- demned. THERAPEUTIC USE OF TUBERCULIN (Abstract) By Charles L. Minor, M.D. ASHEVILLE, N. C. The first vial of tuberculin arrived in New York in 1890, at the time of the conclusion of Dr. Minor's interne service in St. Luke's Hospital, New York. He has constantly used tuberculin during the last seven years, and would be quite unwilling now to be without it. He stated that 20 per cent, is the approximate number of cases upon which it can be used, but that the final word as to the ultimate uses of tuberculin is still to be spoken by sanatorium and dispensary practitioners. Of the large number of tuberculins, the essential thing is that a physician should thoroughly know one of them and its uses. Per- sonally Dr. Minor uses O.T. chiefly, and after that B.E., B.F. and T.R. Tuberculin reduces by 25 per cent, the likelihood of relapse; it improves the physical condition and to a still unascertained degree produces immunity from future attack. It produces a 50 per cent, decrease in the sputum of the patients, as compared with those not being so treated. Consequently its value is real. As a parenthesis, Dr. Minor * Unfortunately no stenographic report of the lecture was made. 21 22 THERAPEUTIC USE OF TUBERCULIN stated that Dr. Von Ruck, of Asheville, believes that he has an immun- izing serum which produces permanent immunity in children. Tuberculin is not necessary in incipient cases but is invaluable in eases of moderate involvement, afebrile cases and those which persist in not making progress toward recovery. It is of utmost assistance in laryngeal cases, also in bone cases and especially in unsoftened glandu- lar cases. Fever is contra-indication, except in the hands of those thoroughly trained in the use of tuberculin. Even then it is not for patients who run over 100.2 degrees. Results of injection must be closely watched and dosage stopped or decreased upon appearance of local reaction (superficial and not deep injection, so that focal signs may be clearly read). Loss of weight usually indicates a period of stoppage with later resumption; tachy- cardia or malaise indicate a suspension of dosage. Blank doses may well be used to allay the fear of timorous patients. Among those most nervous, reactions have occasionally been secured without the use of tuberculin by administering a blank dose. Finally blood-streaked sputum indicates suspension of dosage. Two systems of dosage prevail: First, the gradual increase in size of dose and, second, that designed to secure a minimum reaction. The gradually increasing dosage is believed by Dr. Minor to be the better practice. Beginning with one one-millionth milligram and increasing gradually, avoiding reactions, he gives two treatments per week. But after the size of the dose is increased, once per week is sufficiently often. In case of the appearance of a local reaction, either repeat the same dose or reduce it by half. In case of a focal reaction, reduce it one-half. By observing these two methods a constitutional reaction will be avoided. PNEUMOTHORAX AND REST TREATMENT IN THE MANAGEMENT OF PULMONARY TUBERCULOSIS (Abstract) By John B. Murphy, M.D., Chicago, and Philip Kreuscher, M.D,. Chicago Rest as a treatment in pulmonary tuberculosis is almost as old as the disease itself. The amount of improvement is in direct ratio to the degree of absolute mental and physical rest which the patient obtains. The difficulty encountered in enforcing the strict rest cure is accountable for the period of reaction of two decades ago, and con- sisted in mental and physical activity. This treatment was soon aban- doned in the advanced cases, on account of disastrous results. Clinical observation showed that the body, when permitted to rest, was better fitted to overcome the disease and immunize itself against the toxins. Twenty-five years ago Murphy stated that a patient with an acute tuberculosis of the lung should be treated on the same basis as a typhoid case — ^namely, put in bed absolutely at rest, and watched and dieted with utmost care. After the patient's temperature is normal for a time, he is gradually elevated in bed, and slowly increasing exercise is per- mitted each day. By graduated exercise the patient develops an auto- opsonic index, most favorable to repair. He walks about, begins to do light work, and finally manual outdoor labor without the slightest rise in temperature as a result. The principle of organ rest was first conceived by Carson, of Liver- pool, in 1821, when he advanced the idea that the diseased lung would heal more quickly if the lung itself were put at rest. Carson concluded from his animal experiments that one lung may be coUapsed with per- fect impunity. He believed, furthermore, that pulmonary tuberculosis could be most successfully treated by * ' mechanical means. ' ' In support of this he referred to several instances of history, where in battle sol- diers received penetrating wounds of the chest wall and were cured of an existing tuberculosis. Parolo (1849), Ramadge (1834), Constatt (1843), Wundelich (1856), Ehlers (1867), aU spoke of Carson's pro- posed treatment, but there is no report to show that any of them per- formed the operation on the human. Porlanini, of Padua, next wrote on this subject, 1882. The paper, ' ' Surgery of the Lung, ' ' read by Mur- phy at the meeting of the American Medical Association, 1898, and the subsequent work by Murphy and Lemke influenced Prof. Brauer to take up actively the treatment of pulmonary tuberculosis by pneumothorax. Forlanini and other European physicians and a number of Americans began using the method extensively and have continued up to the pres- ent time. Authorities differ concerning the indications for producing pneu- mothorax. Lenormant says American surgeons have advised employ- 23 24 P^TEUMOTHORAX AND REST TREATMENT ment of artificial pneumothorax in the beginning of the disease. Recent European authors, however, reserve this method for chronic unilateral lesions with cavity formations, in which cases the efforts were unsuc- cessful in a number of cases on account of pleural adhesions. These failures are rare in American statistics (Murphy, 4 per cent, 36 ; Lemke, 5 per cent) on account of the fact that they deal with cases in an early stage. According to Forlanini, rapid development of the disease is a contra-indication, but here again Brauer and Von Muralt have had excellent results. In a recent article Gray, of Chicago, reports sixty- one cases treated in various stages. He prefers the incipient cases and cites Brauer and Spengler's series of eighty-eight cases treated in the late stages, with twenty-three deaths and eight failures, and very correctly makes the queries, "Is it well to wait until the outlook is so desolate ? Is lung collapse such a desperate operation as to be used only as a last resort?" Murphy originally advised the treatment in the earliest stages, as well as in the advanced ones. When a patient comes with an initial hemorrhage or cough, treat him as you would a tuber- culosis of the spine or any other joint — put the part at rest. It is exactly the appendix proposition over again — namely, that the phy- sician and surgeon are waiting for the disease to "ripen" before insti- tuting sufficient measures for its cure. Years ago, in medicine, this procrastination was considered an evidence of genius and conserva- tism. It is really a stigma of ignorance, timidity, and incompetency. "We believe this method most practical in the early stage of apical and monolobular tuberculosis, as there the pathological conditions are such that compression can be easily accomplished and adhesions are not likely to be found. He does not consider that it is indicated or practical in far advanced or chronic cases, where the fibrous tissue deposited will not permit of much compression. Theoretically the dan- gers of compression are: (a) Hemorrhage from wounding intercostal vessels; (b) Injection of gas into an intercostal vein; (c) Infection by impure gas, infected trocar, or improper antiseptic preparation of the chest waU; (d) Rupture of infected foci into pleural cavity through compression of the lung and separation of pleuritic adhesions; (e) Dysp- nea from too large quantities of gas; (f) Puncture of lung with needle; (g) Pleural reflexes resulting in collapse, spasm of the larynx, etc. Only one accident has ever occurred, one case reported by Lemke, where the patient had an air-embolism resulting in a hemiplegia. The quantity of gas should always be large, as much as will be tol- erated without great dyspnea; this quantity can always be injected without a great plus pressure. If compression is indicated at all, real compression is indicated — 60, 150 or 200 cubic inches may be injected at a sitting, if properly administered. Many men inject their patients at periods of from six weeks to six months. Our experience shows con- clusively that considerable absorption takes place in three to four weeks, and that three to six weeks is the time to elapse between injec- tions. The lung must be kept completely collapsed. All authors agree JOHN B. MURPHY, M.D., AND PHILIP KREUSCHEB, M.D, 25 that compression must be kept up a long time. Forlanini says it must be continued indefinitely in an advanced phthisis with disseminated or extensive foci, and in cases in which the other lung has lesions or is threatened. He has shown that a properly proportioned pneumothorax of one side does not injure the non-compressed lung. If the latter is diseased and the lesions not so extensive as to allow compensatory respi- ration for the compressed lung, Forlanini claims that it may heal or be arrested through a mechanism not easily explained but which is com- pletely opposite to that by which a cure is affected in the compressed lung. Apical lesions are not as dangerous as lesions situated centrally. The lesions may in rare instances be aggravated by increased functions or by the amount of toxins liberated, so that treatment may have to be discontinued for a time, or continued cautiously. A number of operative accidents during and after introduction of nitrogen gas have been reported. From our experience we believe that fatal results are due to failures in technique and the absence of knowledge of accidents that can occur in the surgery of the lungs, inde- pendently of pneumothorax treatment. It is suggested that men who expect to follow this line of work should do experiments on animals, as this will give a knowledge of inestimable value in therapeutic work. Death from dyspnea should not occur. If the attending surgeon is on the alert, all that he needs to do to avoid a fatality is to introduce a trochar or a large aspirating needle into the pleura on the side of the pneumothorax and permit air to escape and thus reduce the plus pres- sure, or he can freeze the skin with a little salt and ice, cut it, then with a hemostat spread the tissues, rupture the pleura, open it for the air to escape and thus save the patient. We had but a single rupture of the lung or bronchus into the pleura. The absence of this accident is due to the fact that our apparatus scarcely has a plus pressure, as it carries only % oz. to a square inch. Balboni gives anatomical proofs of recovery through cicatrization of aU destructive lesions of the lung which had been treated with arti- ficial pneumothorax. Forlanini, in the microscopic study of three cases, noticed first atelectasis; second, an extraordinary tendency to forma- tion of hard masses about the bronchi and large vessels in the pneu- monic foci; and third, the formation of a capsule about the lesions and a tendency to cicatrization. Graetz, Brasche and Wurtzen have since confirmed his findings. Murphy has never advocated administering the gas through an incision. Our technique is as follows: The patient is placed in a com- fortable sitting position. If the apex is the site of the lesion, the needle is to be inserted in the fifth or sixth interspace between the anterior and mid-axillary line. If it be a middle or lower lobe tuber- culosis, the injection should be made over the upper lobe, in the fourth interspace, just outside of the mammary line. Ethyl chloride or novo- caine may be used for local anaesthesia. A tenotome puncture should always be made through the skin, to permit easy insertion of the needle 26 PNEUMOTHORAX AND REST TREATMENT and to prevent the introduction of septic fragments into the pleura. It is important, after the needle is inserted and before the tube is attached, to assure oneself that the point of the needle is in the pleural cavity. After a few deep inspirations, if a little air has entered the pleural cavity, there will be a current during both phases of respira- tion. The opening of the needle should be covered with cotton for fil- tering the air that is admitted. Sometimes, even though the point of the needle be within the pleural cavity, the current of gas meets with considerable resistance, due to the fact that unless some pressure is used, it impinges on a small area of lung tissue. To determine that the tip of the needle is in the pleural cavity, a manometer is used, after the manner of Gray. We always use a blunt needle, aspirating size, with an additional opening on the side of the needle near its tip. This per- mits the gas to pass, should the tip be plugged with tissue. After the needle is introduced, it is attached to the tubing leading to the cylin- der containing nitrogen. The quantity of gas varies from 50 to 200 cubic inches. The amount to be given is best regulated by symptoms of distress, dyspnea and displacement of mediastinal contents and dia- phragm. The wound is sealed with collodion and a small firm compress is placed over the puncture, to prevent escape of gas into the subcutan- eous tissue. The patient is placed in bed in a comfortable position. If cough or dyspnea are annoying, a small hypodermic of heroin may be given. Skiagrams should be made before and after injections, to watch the extent of lung collapse and note the pressure on the heart and medi- astinum. Thousands of cases, from the literature, show a complete symptomatic cure and many vast improvements in a great majority of patients. From an experience of nearly 500 cases, with an aggregate of 2,500 injections, by Murphy and his associates, we conclude that artificial pneumothorax should always be made in every case of pulmonary tuberculosis where there is no absolute contra-indication. In reviewing the results obtained in our own cases and those collected from the literature, we may sum up the following advantages of pul- monary rest: The decline or disappearance of fever, diminution and disappearance of expectoration with partial or complete disappearance of the bacilli, gradual increase in weight, lessened frequency of hem- orrhage, great general improvement and the short time in which these changes take place. We are convinced that when the profession as a whole adopts our original plan of early treatment, the percentage of cures will be increased greatly, that the period of convalescence and incapacity will be reduced to a minimum, that accidents in administration will be neg- ligible in number. We take pardonable pride, we hope, in seeing this method universally adopted sixteen years after it was first advanced by us as an effective treatment in pulmonary tuberculosis. This work is carried on in Murphy's clinic by Kreuscher with very gratifying results in a large percentage of cases. THE PRESENT STATUS OF TUBERCULIN THERAPY By Louis Hamman, M.D. baltimore The object of this paper is to provide the practicing physician with a guide to tuberculin treatment. In accord with this object I must assume that the reader is inexperienced in the use of tuberculin, and particularly where methods are concerned, give these in their prac- tical detail rather than in principle. There is a widespread interest in the treatment, but few have reviewed critically upon what evidence its claims to serious consideration are based. Among the general acclaim of tuberculin there are a few dissenting voices and these must be heeded. Before studying the elaborate principle of treatment and the methods of application, one naturally wishes to know the results that have been obtained. It is from this angle that we will approach tuber- culin treatment. Most of the evidence, upon analysis, is reduced to impressions. There are inherent difficulties in statistical studies of tuberculosis that make it arduous to seek evidence in that direction, and animal experiments are far from satisfactory. Almost always the treated animal lives longer than the untreated, but tuberculin has never stopped or even limited an established infection. It is common to read in literature that animals have been "immunized" with different varieties of tuberculin. Such statements are seldom accompanied by detailed protocols and do not bear close scrutiny. Real immunity or resistance to tuberculous infec- tions have been obtained only with living tubercle bacilli. While it would be a great comfort to have tuberculin treatment established firmly upon an experimental basis, still the absence of conclusive results in animals does not settle the question of its value. The value of tuber- culin treatment must rest ultimately upon the clinical results of its administration. Regardless of Koch's injunction that tuberculin was to be used in early and moderately advanced stages of pulmonary tuberculosis, the remedy, after its introduction, was applied recklessly in all stages of the disease. Large doses were then administered, and it is shocking to glance over the clinical charts preserved from those days. The dis- appointment was so keen and the memory remaining so bitter that the weight of more recent conservative work has failed to overbalance the repugnance left in the minds of many physicians. Although the early tuberculin era ended in disaster, still the results obtained even then were not all unfavorable. Recently a prominent clinician has written reminiscently of the immediate and permanent benefits of tuberculin treatment, judged after a sobering interval of nineteen years. Many felt that the downfall of tuberculin was occasioned by its indiscriminate and unreasonable application, and that perhaps more cautious dosage would avoid the dangers, while preserving the beneficial effects. Upon 28 THE PRESENT STATUS OF TUBERCULIN THERAPY this plan many continued the use of tuberculin, convinced that they were getting good results. These results received the endorsement of Koch, and from the time of their publication dates the modern era of tuberculin treatment. All statistical studies of phthisis are surrounded with difficulties, and these are well nigh insurmountable in a statistical study of methods of treatment. Standards of diagnosis are variable, and accurate classi- fication for purposes of comparison is almost impossible. The difficulties of classification reside chiefly in the lack of correspondence between the extent of the disease and the severity of symptoms. Until the past few years. Turban's classification, based entirely upon the extent of pul- monary involvement, was in general use. More recently the National Association has proposed a schema which takes into account signs and symptoms which have been universally adopted. Although classification of phthisis is inadequate, an estimate of the results of treatment are still more unsatisfactory. More satisfactory standards of comparison have recently been proposed, as: (1) Working ability; (2) disappearance of tubercle bacilli from the sputum; (3) duration of life. They are arranged in inverse order of their importance. To overcome the influence of spontaneous variation in the course of the disease a large number of patients should be studied. Side by side with the tuberculin treated patients an equal number of patients as nearly similar as possible, should be observed under identical conditions, save that tuberculin is withheld. Many statistical studies to which unde- served esteem has clung dwindle into personal impressions, and as such they retain their just value. I now present the sputum statistics. They speak strongly for the healing effect of tuberculin: Author Open Cases Tuberculin Treated Lost Bacilli in the Sputum Not Treated With Tuberculin Lost Bacilli in the Sputum Kremer 110 Of 55 cases 41% Of 55 cases. .29% PhiUipi 126 II stage. ni stage. 58% 31% n stage, m stage. .19% . 7% Turban 159 86 eases 47% 24 cases 27% Brown I stage. n stage. 67% 44% I stage, n stage. .64% .24% Baudelier 202 129 cases 64.9% 12 I stage 100% 113 ni stage.... 50% Lowenstein 682 369 cases 53% Average of 20 years' untreated e x p e - rience only 15% Baudelier has classified his 500 cases also from the point of working capacity. — Total — Stage I Stage H Stage III Cases Per Cent Per Cent Per Cent Per Cent Complete earning capacity on discharge. . . . 500 69.8 90.4 80.7 32.8 Sputum changed from positive to negative. . 202 63.9 100 87.3 44.0 It is seen from the table that statistics based on sputum becoming LOUIS HAMMAN, M.D. 29 negative afford a real evidence of improvement. The parallelism between the two sets of figures is close. Favorable reports of tuberculin treatment in so-called surgical cases of tuberculosis are no less numerous. Tuberculous larjmgitis is a thankful field for this method, and also tuberculous lesion of the eye. In serous membrane tuberculosis, many find tuberculin of value. Most surgeons advise post operative treatment, with tuberculin in renal tuberculosis. Many investigators commend tuberculin in tuberculous adenitis upon the basis of excellent results observed in a large number of cases. From the consideration of this evidence the following con- clusions are warranted. Tuberculin is not a cure for tuberculosis, else such a detailed consideration were unnecessary. However, in many instances it produces healing, and recovery is more certain and more lasting than without it. Such a conservative estimate of its influence ranks tuberculin as a favorable factor in the management of the dis- ease, a favorable factor as rest and diet are favorable factors. This being its position, it behooves us to give it wide application, but not to the exclusion of other favorable factors, but in combination with these. All tuberculin may be divided into three groups: (1) Those pre- pared from the culture media in which tubercle bacilli have grown; (2) those prepared from the bacilli themselves; (3) those prepared by various methods of extracting the tubercle bacilli. The principal mem- bers of group (1) are: Koch's Original or Old Tuberculin, O.T. ; Denys' Bouillon Filtrate, B.F. ; Jochmann's Albumose Free Tuberculin, A.F. ; Koch's Bacillen Emulsion, B.E. ; Koch's Tuberculin Residue or New Tuberculin, T.R. ; Beraneck's Tuberculin; Von Ruck's Watery Extract; Landman's Tuberculol. It mil be seen from this list that there has been a feverish strife to improve Old Tuberculin. Two considerations prompted these efforts: (1) To attempt, under the assumption that they are many, to include all the potent portions of the tubercle bacillus in the preparation; (2) to attempt to remove supposed deleterious sub- stances from the culture media of the bacilli themselves, while pre- serving the beneficial or immunizing substances. We know too little about the constitution of tuberculin to identify it by any chemical test. There is only one characteristic of tuberculin that is absolutely specific — namely, the power to produce certain reactions in tuberculous animals. Briefly, the features of this reaction are redness and swelling at the point of injection, inflammatory reaction about the lesion, and fever and constitutional symptoms. Recent investigations show conclusively that the potent substance in tuberculin that causes the reaction is the protein of the bacillus. A product containing this protein is a tuber- culin, and no substance that does not contain it can be so classified. There is no other characteristic mark of tuberculin. That settles at once all discussion about the value of many different tuberculins. All are satisfactory if they contain the protein and the test of the 30 THE PRESENT STATUS OF TUBERCULIN THERAPY presence of these proteins is their ability to produce the tuberculin reaction. Different strains of tubercle bacilli produce widely different tuber- culin. The variation is in strength alone, the character of their effects being invariably the same. Romer, after extensive investigations of effects of tuberculin from human, bovine and fowl tubercle bacilli upon animals (guinea pigs, cattle, chickens and rabbits) infected with human, bovine and fowl bacilli, concludes that there is no essential difference in the character of effects they produce. Indeed, human and bovine tuberculins are so identical in their action upon infected animals that we may neglect to ascertain their source. Practically all tuberculins are efficient. Tuberculin acts by stimulating the patient to elaborate pro- tective substances, or to an inflammatory reaction about the area of infection. The most suitable patients for treatment are those with small localized lesions that are not producing constitutional symptoms — namely, pulmonary tuberculosis, tuberculosis of the glands, bones, eye, etc. Many patients have reaped a measure of improvement from hygienic dietic treatment, but then for months remained stationary. Tuberculin is often just the stimulation they need to start them upon a course of rapid improvement. Entirely unsuited for tuberculin treatment are patients exhausted by the disease or with actively pro- gressing infection. Advanced cases with fever and emaciation and those with acute disseminated tuberculosis are to be excluded. Between the groups definitely suitable and definitely unsuitable for treatment is the large class of border-line cases. In many of these, when tuber- culin is cautiously given, it does no harm ; and in many cases it must be started tentatively with a readiness to discontinue or push on according to the result obtained. When patients with fever fail to respond to pro- longed rest in bed, in my experience, they usually fail to respond to tuberculin. Although there are innumerable variations in the administration of tuberculin these methods can be reduced to two: (1) Giving small doses and repeating the same small dose at stated intervals; (2) start- ing with small doses and progressively increasing the dose, varying the time, interval and rate of progression to suit individual conditions. One plan, advocated by Lowenstein, is to reach high doses of tu-berculin in the shortest time possible. Another plan, represented by Trudeau, Sahli and Denys, aims to arrive at as high grade of tuberculin tolerance as possible, but the reaching of high doses is not the ultimate object. I agree with Sahli that we succeed in reaching as high doses by the mild plan as by the more daring plan, that the improvement is equally satisfactory, and that less danger is run. Briefly, the best method of using tuberculin is to give increasing doses with the purpose of producing the greatest amount of focal stimulation without liberating general reaction. For practical purposes we find the simplest method is to prepare a series of dilutions, each being one-tenth the strength of the former. LOUIS HAMMAN, M.D. 31 Bottle No. I contains pure tuberculin; No. II, 9 c.c. diluent and 1 c.c. tuberculin ; No. Ill, 9 c.c. diluent and 1 c.c. of II ; No. IV, 9 c.c. diluent and 1 c.c. of III, etc. The diluent is 0.8 per cent, salt solution with 0.25 per cent, carbolic acid. To give 1 c.mm., give 0.1 c.c. of bottle III, 5 c.mm. 0.5 c.c. of III, etc. The dilutions should be kept in a cool dark place, when not in use. Fresh dilutions should be made every two weeks; we note no change in strength in this period. To make the dilutions one needs a flask for the sterile salt-carbolic solution, a number of wide-mouthed glass-stoppered bottles and two pipettes, one with a relatively large bore accommodating 10 c.c. and graduated in tenths of a c.c, one with a fine bore accommodating 0.1 c.c, and grad- uated in hundredths of a c.c. The injections are made subcutaneously, so when local reaction occurs it can be readily detected. The syringe and needle should, of course, be boiled before use, and care be taken that tuberculin solutions remain sterile. The skin needs only to be rubbed with alcohol. Other routes of administration have been proposed. Intravenous injections first made by Koch run danger of severe reactions. The oral route was recom- mended by Freymuth; its effects are uncertain. Other methods not in general use are by inhalation and intrabronchially, cutaneously, and directly to cutaneous tuberculous lesions. My experience has been mainly with B. F. and 0. T. For B. F., I consider 0.0001 c.mm. the dose generally suitable for beginning treat- ment. For 0. T., 0.001. For T. R. and B. E., 0.001 to 0.005 c.mm. T. R. contains 10 mg. and B. E. 5 mg. of ground bacilli in each c.c. It will be seen that the initial dose of all tuberculins is in the neighbor- hood of 0.001 c.mm. Severe reactions never occur after this dose, and mild reactions can do no harm. . . . When shall the second dose be given? The empirical results of clinicians have made the selection of from three to five days almost universal. Our routine at Johns Hopkins Hospital is to administer small doses twice a week until we have reached the level of the patient's tolerance, when we change to the week interval. If the patient shows no evidence of intolerance we change to the week interval when 10 c.mm. is reached. Our aim is the greatest amount of focal stimulation without liberating general reactions. The symptoms of tuberculin reaction are: (1) The general constitutional symptoms; (2) the focal reactions or changes occurring about the diseased area; (3) the localized reaction occurring at the point of injection. The elevation of a few fifths of a degree above the usual maximum tempera- ture should receive careful consideration and the relation to the injection should be studied. If the temperature has been constantly subnormal with wide daily variations in range, under treatment the mean level may rise gradually toward normal and the oscillations become smaller. Such an occurrence must be viewed as a favorable effect of the treat- ment. Temperature rise occurring during tuberculin treatment and not due to the injections may be grouped in three classes: (1) Due to 32 THE PRESENT STATUS OF TUBERCULIN THERAPY external influence, over-exertion, fright, emotion, an unexpected visit, animated conversation or excitement, as over a game of cards. (2) All patients with tubercidosis are susceptible to variations in temperature that are not easily explained and these are interpreted as evidences of auto-inoculation. On account of changes, probably in circulatory, about the lesion, absorption is suddenly increased and the patient has endo- genous tuberculin reaction. (3) Inter-current infections are a fertile source of temperature elevation. Loss of weight as an isolated symptom is sometimes the first warning of intolerance. It is valuable as a sign of overdosage late in the treatment. The focal reaction is of some value in guiding dosage when the lesion is situated externally. I regard the appearance of fresh rales as the only reliable mark of pulmonary focal reaction. Local reaction is the most valuable of the three in calling our attention to the proximity of the border-line tolerance. Local reactions must be looked for carefully, and the site of the previous injection always inspected before the following dose is administered. All regions of the body are not equally sensitive to tuberculin. Local reactions occur much earlier when injections are made in the arm than when the back is selected. For this reason we prefer the subcutaneous tissue of the back. During the preliminary period of small dosage it is safe and advisable to double the amount of each injection until symptoms warn that the level of tolerance has been reached, or if these do not appear until 0.1 c.mm. is reached. Reactions occur more commonly to doses from 0.1 to 10 c.mm. than at any other level. It is the period that requires the greatest vigilance, for when 10 c.mm. is passed, progress from then is usually unobstructed. When 0.1 c.mm. is reached, the dose may be increased by tenths. Thus we would give 0.1, 0.15, 0.25, 0.3, 0.4, 0.5, 0.7, 1.0, etc. This plan is simple, and in practice works well. If symptoms of reaction appear in the absence of a general reaction, the further course will depend entirely upon the patient. (1) In a number, by slowly and cautiously increasing the dose, this early period of hypersensitiveness is soon overcome and thereafter we can rapidly increase the dose. (2) The patient's sensitiveness may remain at a remarkably constant level, so that any effort to go beyond a certain dose is invariably followed by a general reaction. Such constant hyper- sensitiveness may persist for years. (3) There are patients who per- sistently remain at a given level, but under prolonged treatment grad- ually acquire a lower hypersensitiveness, and the doses may be gradually increased. Such changes are marked by general improvement in the patient's condition. There is no absolute terminal dose. Most observers cease raising the dose when 1,000 c.mm. is reached. Often this dose is exceeded. When this maximum is reached some physicians advise repeating it indefinitely at 10 to 14-day intervals; others advise breaking off the treatment temporarily. If it is decided to give a second course of LOUIS HAMMAN, M.D. 33 tuberculin, treatment may be pushed more vigorously. A course of treatment extending over a period of six to twelve months does not cure tuberculosis. Often the symptoms completely disappear, though the lesion persists. In others the lesion may apparently be healed, but we fear a fresh outbreak. Most clinicians are in favor of repeated courses of treatment. Tuberculin tolerance developed under treatment persists for a long time, often unabated for a year. Therefore treatment may be begun at higher doses and rapidly increased. X-RAY DIAGNOSIS OF TUBERCULOSIS OF THE LUNGS AND BRONCHIAL GLANDS (Abstract) By Hollis E. Potter, M.D. CHICAGO 1. Radiography is not a competitor of other clinical methods, but an additional means of diagnosing lung tuberculosis. 2. In certain cases a positive diagnosis by X-rays is possible, where the best of clinicians can only write "suspected." The reason for this is that the signs and symptoms do not always run parallel with the pathology. The X-ray procedures are aimed directly at the pathology. 3. Certain other cases give presumptive signs and symptoms, with no positive X-ray findings. In a long series of cases the clinical and X-ray findings are found to agree in the main. 4. The tubercular invasion is demonstrable by Roentgen rays on account of the increased density of the tubercle and its collateral inflam- matory process as against the transparent air-filled areas of normal lungs. 5. Fluoroscopy and radiography, especially stereoscopic radiography, both have their advantages in the X-ray examination. By fluoroscopy one easily sees the gross lesions, the diaphragmatic movements and the degree of expansion of the several lobes individually. By critical radi- ography one may demonstrate the finest granular deposits not easily seen fluoroscopically. A thoroughgoing examination includes both methods. 6. The early radiologic signs of pulmonary tuberculosis are: (a) Lessened diaphragmatic excursion on the affected side. (b) Failure of the affected lung or lobe to "light up" during deep inspiration. (c) Positive demonstration of pulmonary infiltrations of the type usually associated with tuberculosis. In early cases these deposits may appear like the shadow of dried leaves on a branch, like grapes in a cluster or as discrete unconnected masses with a granular or flocculent appearance. (d) Later cases are also variable in their appearance, showing larger masses and perhaps large areas of consolidated lung. 7. Healed lesions are on the whole more discrete than active ones, being composed of denser, more homogeneous, retracted tissue. In many cases the activity of the process can be estimated. 8. Valuable evidence is usually obtained regarding cavity, pleural effusions, pleural thickening, pneumothorax, tubercular pneumonia, etc. 9. The differential diagnosis between tubercular shadows and those seen in bronchiectasis, and certain cases of broncho-pneumonia, blasto- mycosis, and actinomycosis, is sometimes difficult. 10. Bronchial gland tuberculosis is more difficult to interpret on 84 X-RAT DIAGNOSIS OF TUBERCULOSIS 35 accoTint of the normal existence of a pronounced hilus shadow and the frequent occurrence of non-tubercular enlargements of the hilus glands by anthracosis, etc. Increased hilus shadows have more diagnostic importance in children than in adults and are especially important if associated with definite pulmonary infiltrations at a distance from the hilus. DISCUSSION Frances C. Turley, M.D., CMcago: The preceding speaker has so thoroughly and competently covered the subject of the Roentgenolog- ical examination of the lungs and bronchial glands for tuberculosis that but little is left to be said, except a few facts in confirmation of the statements already made. Undoubtedly a combination of the two methods, fluoroscopy and the Eoentgenograms, gives the best results: — fluoroscopy, for the observa- tion of the thoracic walls and their contents in motion, for locating gross lesions and differentiating fluids from lung consolidations ; and the Roentgenogram, because it is considered by many of the best Roent- genologists as an absolute necessity for the detection of the early lesions of incipient and doubtful cases. It may be said in view of this opinion that no case should be dismissed from an institution as cured until a thorough search has been made with the X-ray for an active lesion. Fluoroscopy is less expensive than radiography and may thus prove very valuable for the observation of the progress of cases diagnosed but under treatment. It is a fact that the X-ray will show in a Roentgenogram more clearly the extent and the character of the involvement of a tubercu- lous lung, in some cases, than can be determined by the most careful physical examination. It is also a fact that the lungs may be exten- sively involved in a tuberculous process and no tubercle bacilli be found in the sputum, though present in the air vesicles. In such cases there is no doubt about the value of the Roentgenogram because such lesions show definitely tuberculous, in almost, if not quite, all cases. At times the question of pulmonary tuberculosis is brought to the attention of the physician when a thorax is examined for other lesions, on account of the striking picture presented to the eye, when such a condition had not been previously under consideration as a cause of the symptoms. While the following opinion may not pass unchallenged, yet it is worthy of consideration, namely, nitrogen gas should not be used to collapse a lung until the chest of the patient has been subjected to a recent careful Roentgen examination in order to determine the relative condition of the two lungs, and as far as possible the condition of the pleura, and the number and location of pleural adhesions, if any, on the side chosen for operation. In conclusion the suggestion might be 36 X-RAY DIAGNOSIS OF TUBERCULOSIS made that the operation be carried out under fluoroscopic observation if it were not that such observation requires total darkness. However, a safe technique might be developed. James T. Case, M.D., Battle Creek, Michigan: In incipient tuber- culosis the writer holds that the Roentgen evidence is of the greatest value; not in itself alone, but in conjunction with the other findings of clinical research. This is true of the X-ray findings in any disease. It is recognized that sometimes the X-ray evidences are so concrete one may say at once that the condition is thus and so, making a definite diagnosis. But even in these cases, for the sake of scientific complete- ness and accuracy, the X-ray findings should be carefully correlated with the results of other methods of research. So it is also in pulmonary tuberculosis. In the very early stages, when there are as yet only catarrhal changes such as only the most expert can detect by ear or touch, it is likely that the X-ray findings will not be decisive. The most one may be able to say is that there is evidence of a pulmonary infection, the exact nature of the infecting agent not being recognizable from the X-ray examination. When, however, caseation has supervened — and this is fortunately a comparatively early development — the X-ray findings are at once decisive as to the extent and location of a pulmonary infection which is in all probability tuberculous, though again one may not be able to place himself defiidtely on record that the infecting agent is Koch's bacillus. The geographical disposition of the signs of resistance to infection, and still later perhaps the signs of defeat in the face of infec- tion, in pulmonary tuberculosis, are often so characteristic that one may say definitely that the lesion is tuberculosis. In more advanced stages of the disease, the X-ray examination is less essential as a diagnostic agent, but it becomes more and more a confirmatory means, especially in helping to map out the extent of a frank lesion or in estimating the virulence of the process in the various foci of infection. Of especial value is the X-ray examination when the infection is central, or masked by emphysema and other pulmonary non- tuberculous lesions. The Roentgen findings are of notable value in the study of pleural thickenings, pleural effusions and exudates, and espe- cially in inter-lobar affairs. Pulmonary malignancies may usually be differentiated by the Roent- gen findings, especially when there are signs elsewhere indicating the site of the primary lesion. The technic is of the greatest importance. Fluoroscopic examination, so essential in gastro-intestinal work, is here of relatively small value, at least in the incipient stage where the aid of the X-ray is most needed. Nevertheless the screen study is essential in all cases for the proper estimation of the action of the diaphragm; the extent of interference due to adhesions of the diaphragm and pericardium ; the degree to which certain involved areas light up on comparison of inspiration and expira- X-RAY DIAGNOSIS OF TUBERCULOSIS 37 tion; the determination of small amounts of fluid in cavities and in the costo-phrenic angles. The ordinary single Roentgenogram is not of much value in exact studies, but the stereoroentgenogram is of the greatest possible value. It is sometimes necessary to make stereoroentgenograms both anteriorly and posteriorly, but the anterior stereoscopic pair is ample except in very important cases where it is absolutely essential that the Roent- genolist make a definite statement as to the presence or absence of a pulmonary lesion. The speaker has found of highest advantage close association with a splendid physical diagnostician to whose accuracy and painstaking exactness he wishes to testify. By thus combining and correlating the results of physical and Roentgen research, the abilities of both clinician and Roentgenologist are sharpened to the utmost, and there is promise of much progress in the near future. EELATIVE IMPORTANCE OF BOVINE AND HUMAN SOURCES OF INFECTION IN THE PRODUC- TION OF TUBERCULOSIS By M- P- Eavenel, M.D. columbia, mo. I do not need to say that it gives me a great deal of pleasure to be here with the Eobert Koch Society and to speak to you on this occasion. Dr. Sachs asked me to speak on this subject — Bovine Tuberculosis — which has been a special study of mine for a number of years. I remember very well that Dr. Welch of Johns Hopkins asked me in 1912: "Do you not think that the time has come when we can stop discussing this question of the relation between bovine and human tuberculosis, at least to the extent of not making it a prominent subject in our meetings?" I told him that I felt to a certain extent that this could be done, and yet the question crops up year after year. Not a legislature meets in any state of the Union that the question does not come up in one form or another. We are constantly confronted with the "cow question," as Dr. Favill has called it, and I could spend very much more time than you would care to listen, in talking on bovine tuberculosis as an economic scourge, as a farmers' question, a "cow question," and the cost to us, to the United States, and to the world in general, and also, I believe, a factor in the high price of living at the present time. However, those present are interested in it chiefly on account of its relation to public health, and on that phase of the question I am going to spend all my time today. The history of this controversy dates back to 1901, at the British Congress on Tuberculosis. Before that time we were practically a unit in believing that tuberculosis was the same in whatever animal seen and in whatever form in any animal. This was the belief of Villemin, who in 1865 first showed that tuberculosis was a communicable disease. Koch said that Villemin did thorough and methodical inoculation experiments, using material from man and cattle, "and proved experi- mentally the identity of the latter disease with human tuberculosis." As a result of his own experiments Koch says: "The perfect identity and unity of the tuberculous process in different kinds of animals can- not be doubted." Koch also stated, in his first papers: "It seemed to me, however, not improbable that though bacilli from various forms of tuberculosis, perlsucht, lupus, phthisis, etc., presented no differences microscopically, yet that in cultures, differences might become apparent between bacilli from different sources. But although I devoted the greatest attention to this point, I could find nothing of the kind. I was not able to demon- strate any differences in the effect of inoculation with material derived from varieties of the tuberculous process, as miliary tuberculosis, 38 M. P. RAVENEL, M.D. 39 phthisis, scrofula, fungus, inflammation of joints, lupus, perlsucht and other forms of animal tuberculosis." The whole world believed until 1901 that the different forms of tuberculosis were the same, except that in 1896 Dr. Theobald Smith pointed out certain differences between cultures of human bacilli and bovine bacilli. This work was extended and enlarged upon in 1898. The chief differences which Dr. Smith observed were as follows: (1) The human bacillus is very much easier to grow on artificial culture media than the bovine. (2) The human bacillus is long, slender and stains unevenly, whereas the bovine bacillus is short, thicker, and stains evenly, not showing vacuoles. (3) Most important of all, the bovine bacillus, for all experimental animals, shows a virulence very much greater than that of the human. The general belief until 1901 was that bovine and human tuberculosis were the same and that the bovine disease could be transmitted to human beings. At the British Congress on Tuberculosis, Koch made the follow- ing statements: 1. Human tuberculosis differs from bovine and cannot be trans- mitted to cattle. 2. Though the important question, whether man is susceptible to bovine tuberculosis at all, is not yet absolutely decided and will not admit of absolute decision today or tomorrow, one is, nevertheless, already at liberty to say that if such a susceptibility really exists the infection of human beings is but a very rare occurrence. I should estimate the extent of infection by the milk and flesh of tuberculous cattle and the butter made of this milk as hardly greater than that of hereditary transmission, and, therefore, do not deem it advisable to take any measures against it. In regard to the first of these statements it has been repeatedly shown that cattle can be infected with human bacilli. In regard to the second statement and the comparison to hereditary transmission, it may be stated that tuberculosis is not an hereditary disease. The literature of all the world shows only about twenty-five cases of true hereditary tuberculosis; even in animals it is rare. The possibility of hereditary tuberculosis is recognized as an academic fact but practi- cally it plays no part in the spread of the disease. Koch's statement was equivalent to saying that there was no danger from bovine tuber- culosis. Koch's opinions raised a storm of opposition. He was the greatest authority in the world on tuberculosis and such an opinion, if true, would have upset not only aU of our ideas, but the laws which almost all civilized nations had enacted to protect human beings against the bovine disease. The English Government soon appointed a Royal Com- mission, and the German Government an Imperial Commission. The latter was presided over by twenty-five of the leading professors of the German Empire, including Koch himself. 40 SOURCES OP INFECTION EN" TUBERCULOSIS The English Commission examined 108 cases, of which 84 showed human infection, 19 bovine, and 5 both human and bovine. In other words, 22 per cent of all their cases showed bovine infection. If we analyze these cases as to the location of the disease, we find that there were 38 cases of cervical gland and abdominal tuberculosis. Of these 17 were bovine, 19 human, and 2 both human and bovine. Taking those showing abdominal tuberculosis alone, there were 29 cases, 14 of which were bovine, 13 human, and 2 both human and bovine. The German Commission reported that of 84 children examined by them, 21, or 25 per cent, had derived their infection from bovine sources. Against this laboratory work the German Commission reports a col- lective investigation done, I beHeve, mostly by correspondence. Six hundred and twenty-eight persons who are said to have been in the habit of drinking milk from tuberculous cows were examined. One group containing 360 persons, among whom were 151 children, drank the milk uncooked. Clinical examination showed only 2 cases of tuber- culous adenitis and 14 cases of suspected tuberculosis. The second group consisted of people who drank the milk from tuberculous cows after heating. Among these there were 13 cases of suspected tuber- culosis. I have never been able to place much confidence in clinical examinations of this sort and do not consider that this investigation has much value. In the first place it is entirely probable that many cases of infection escaped clinical observation. We know that many people are infected with tuberculosis and recover without showing clinical symptoms. In the second place, it is impossible from clinical observation to tell the difference between human and bovine tuberculosis. The British Royal Commission has shown that it is impossible to tell the difference between the two even by microscopical examination of the tissues involved — that the process is essentially the same whatever the origin of the infecting organism. "We have had a most striking object lesson in the United States showing the danger of depending on clinical observation. In the City of New York the leading pedia- tricians for many years followed Koch, claiming that there was no danger to children from drinking the milk of tuberculous cows. The work of Doctors Park and Krumweide have shown how fallacious this idea was. Taking the City of New York in general, these authors examined 88 cases, of which 77 were human and 11 bovine, showing 121^ per cent of bovine infection. At the Babies' Hospital, where 63 cases were examined, 59 were human and 4 bovine, a percentage of 6 1-3 bovine. At the Foundling Hospital 9 cases were examined, of which 4 were human and 5 bovine, or 55 per cent bovine. In the Foundling Hospital cow's milk was used exclusively, and these figures in my opinion repre- sent the real danger from unprotected cow's milk. These examinations were made on children who had died of the disease. It is well known that tuberculosis often causes affections of bones, joints, and glands, M, P. EAVENEL, M.D. 41 which are not fatal but which lead to more or less permanent deformity and injury. If these cases are taken into consideration, the percentage of bovine tuberculosis is very much higher, probably about 30 per cent of those suffering from the disease. A study of age periods is also very instructive. Of nine adults examined by Dr. Park, all showed the human infection. Of 27 children from 5 to 16 years of age, 19 showed human infection and 8 bovine. Of 18 children from birth to 5 years of age, only 6 showed human and 12 showed bovine infection. Just why this increased susceptibility to bovine infection is seen in children, and especially children of the younger age, I am unable to explain. It is interesting, however, to observe that it corresponds with the age at which cow's milk forms a considerable portion of the diet. AU workers along these lines have found figures corresponding to these, and we are able to say that children, during the first five years of life, are more suspectible than when older, and after the age of 16 our figures show even a smaller proportion of bovine infection. The figures collected by Dr. Park from laboratories in many countries show the relation of bovine to human infection: Cases Examined Human Bovine Adults 787 777 10 Children, 5-16 years 153 117 36 Children, 0-5 years 280 ' 215 65 During the last few years very interesting work has come to us from Edinburgh. The first report is published by Mr. Fraser. This work has an interesting and pathetic history. Mr. Stiles, the well- known surgeon of Edinburgh, was caUed to see a child suffering from surgical tuberculosis. The case was too far gone for interference, and soon went to death. Mr. Stiles gave as his opinion that the child had been infected by milk. This was considered impossible by the parents, as they had their own cows, which were said to have been tested with tuberculin. Mr. Stiles persisted in his opinion, telling the parents that if the cows had not reacted it was probably because the disease was too far advanced. On slaughter, both cows were found to be in a condition of advanced tuberculosis, and one had tuberculosis of the udder. The bereaved father then gave money and asked that a study be made of this question. Mr. Fraser examined 67 children 12 years of age and under, suffering from various forms of surgical tuberculosis. Forty-one of these showed the bovine tubercle bacillus, 23 the human bacillus, and 3 both human and bovine. Analyzing these cases by age periods, we find that in children under five years of age there were 47 cases, 32 of which showed bovine infection, 12 human, and 3 both human and bovine. More recently Dr. MitcheU of Edinburgh has carried out an investi- gation on cervical gland tuberculosis. Seventy-two consecutive cases were examined by him. Sixty-five, or 90 per cent, showed bovine infec- tion, and only 7, or 10 per cent, showed human infection. Among these 42 SOURCES OF INFECTION IN TUBERCULOSIS there were 38 cases in children under 5 years of age, and of these 35 showed bovine infection and only 3 human. In America Dr. Lewis has examined 15 cases of cervical gland tuberculosis, his patients ranging as high as 32 years of age. Among these 9 showed bovine infection and 6 human. Those showing bovine infection had an average age of 8i/^ years, while those showing human infection averaged 17-2/3 years. Again we note this striking fact that the younger the child is, the greater apparently is the danger from bovine infection. I know of but one piece of work which does not accord with these general facts — that of Gaffky of Berlin. He examined 78 children, the ages not given exactly, . and among these found only 3 cases of bovine infection. These figures do not agree with those given by the German Imperial Commission or by other reports from Germany. The German Imperial Board of Health examined 3 cases of primary cervical tuberculosis and found that two of them were bovine and one human. "Weber examined five cases II/2 to 8 years of age and all of them showed bovine infection. I will not weary you with further figures, and simply repeat the statement that bovine infection seems much more common in younger children than in older ones, and more common in older children than in adults. I know of no explanation for the apparent immunity of adults to infection by the bovine germ. We have abundant evidence that when this germ is inoculated into wounds, as not infrequently happens to veterinarians and butchers, it produces exactly the same changes as the human germ. It is well known that such inoculations, whether human or bovine, usually remain local and do not produce generalized tubercu- losis; yet we have instances of such infections, with the bovine germ extending up the arm and producing generalized tuberculosis with death. I know of no good reason why infection through the digestive tract should not also take place in adults as well as in children, yet the fact remains that laboratory work does not often demonstrate the presence of the bovine germ in adults. The question then arises, can prolonged residence in the human body change the morphology and characteristics of the bovine germ so as to make its origin unrecognizable? I do not hesitate to express my belief that this can and does take place. I acknowledge freely that of all germs the tubercle bacillus seems to retain its characteristics as well as its virulence more strongly than any other. Yet we have experi- mental proof that such a change does take place. Dr. Leonard Pearson and myself changed, by passage through five calves, a typical human germ into a bovine germ typical in every respect. I know that there is a possibility of error in this experiment but every precaution was taken against error. The calves were tested with tuberculin, kept in a new stable with cement floor and walls, and isolated from every known M. P. RAVENEL, M.D. 43 source of infection. Tuberculosis is such a slow disease that there is always a possibility of some error creeping in, in spite of precautions. Our results have been confirmed, however. Eber of Leipzig has reported experiments similar to ours, with the same results. The English Royal Commission, in studying the tubercle bacillus isolated from cases of lupus which did not correspond either to the human or to the bovine, in two cases changed the character of the bacillus by passage through rabbits and calves until it became a typical bovine. Further than this, we know that the avian tubercle bacillus is derived from the mammalian type, and that the tuberculosis of fish and of the blind worm of MoUer have a similar origin from the mammalian bacillus. Both of these types of the tubercle bacillus differ very much more markedly from the mam- malian type than the bovine and human differ from each other. The tubercle bacillus demands a constant temperature at or about that of the body, yet by residence in fish and in the blind worm it can be so changed that it will no longer grow at body temperature, but must grow at ordinary room temperature. In view of these facts, which are acknowledged by everyone, it does not seem to be going very far out of the way to hold that the tubercle bacillus can be made to change its characteristics, its morphology as well as its virulence by prolonged residence in a given soil. If it does not so change, it is an exception to all known germs. If such change takes place, it then follows that the type of bacillus which is oftentimes isolated from the human being and which presents only the char- acteristics of the human germ may in reality be a bovine germ which has changed its type so that its origin is no longer recognizable by our usual methods of experimentation. The great question now may be asked : What proportion of the cases of tuberculosis occurring in human beings which we see in our actual life and in our practice are due to bovine infection? In other words, what is the relative importance of infection from bovine sources to infection from human beings? I do not believe that we have facts enough before us to make a positive statement concerning this matter. We certainly must acknowledge at the present time that infection from our fellow man is the most common source of infection in human beings, especially in adult life. For children the most sceptical must acknowledge that bovine infection is quite frequent. In New York City the work of Doctors Park and Krumweide has demonstrated that at least 300 children die in that city every year from bovine infection, and Dr. Park very justly says that there is no reason for believing that New York occupies any better position in this regard than other large cities of our country. The most recent estimate I have seen is that of Dr. Lawrason Brown of Saranac Lake. He considers it certain that 8 per cent of all cases of tuberculosis that we see are of bovine origin. Accepting this, it means that at least 16,000 people die in the United States every year from bovine infection. This mortality is certainly 44 SOURCES OF INFECTION IN TUBERCULOSIS great enough to make us earnest in our efforts to guard the people against the bovine disease. Apart from the death rate, a very much larger number of persons suffer from deformities due to tuberculosis, such as humpback, hip joint disease, etc. The exact number of these cannot be accurately estimated. If what I have told you is correct — and I feel that I have given you proofs of everything claimed — the lesson to be learned is a clear one. We stand for clean milk — milk that comes from cows known to he healthy — milk which is drawn and handled in a cleanly manner. We must support our health officers in their work for clean milk, and educate the public in general to support such demands. The burden of the proof must be put on the producer. It will not suffice to take milk which we do not know to be diseased. We must demand that milk be served to our communities which comes from cows known to he healthy. The value of clean milk, to children particularly, is well known to aU. Its influence in the prevention of tuberculosis will be equally great. PRESENT STATUS OF IMMUNIZATION AGAINST TUBERCULOSIS By Gerald Bertram "Webb, M.D. colorado springs, colo. The term ' ' inmninity, " as you know, originates in the Latin ^'im- munitas," meaning "free from service." We apply it to the condition of an animal or human being which does not allow of attack by bacteria or other parasites which can cause disease. We have a true or natural immunity such as man possesses against such diseases as chicken or hog cholera, or an acquired immunity such as we possess against smallpox, after previous vaccination with cow- pox. Then, too, we have a special tissue immunity in view of the fact that certain organs are more difficult to infect than others. For instance, we infect a guinea pig with tubercle bacilli. We rarely find infection in the kidneys. In calves or rabbits, on the other hand, so infected, we usually find tuberculosis in the kidneys. In the human being it is rare to find tuberculosis of the muscles or of the large blood vessels. The history of immunity studies in tuberculosis is especially bound up with American researches. To the French must be given credit for the discovery that tuberculosis is a transmissible disease. It was proven by Villemin long before the advent of the immortal Pasteur and long before the discovery of the bacillus of tuberculosis by the great genius of Koch. It is to be recalled that the great Jenner lost a son from tuberculosis and in his biography we read that he, too, tried to discover the cause of tubercles. Koch began the studies of tuberculosis immunity by the employment of living cultures, and we can never repeat too often the laws he discovered. " If a normal guinea pig is inoculated with tubercle bacilli, the point of inoculation very soon closes. After ten to fourteen days there appears at this site a small hard nodule which finally ulcerates. This shows no tendency to heal and remains so until the death of the animal. If, however, an already tuberculous guinea pig is so inoculated, while the point of inoculation also closes, no indurated nodule appears. Instead a necrotic process of the skin sets in, after the second day, which finally terminates in the casting off of the slough and the formation of a flat ulceration that heals rapidly. It does not matter whether living or dead tubercle bacilli are used for the second infection." In this research, then, we have a beginning of our knowledge of immunity in tuberculosis, for the first infection, although fatal in time, evidently set in process immunity reactions which were indicated after the second inoculation. These studies led to the development of tuberculin and to attempts, which all failed, to prove immunity by the inoculation of dead products 45 46 PRESENT STATUS OF IMMUNIZATION AGAINST TUBERCULOSIS of the germ. Koch's final words on immunity in tuberculosis are worth recalling : "We shall never obtain better results with non-living bacilli;" and "We shall not succeed in habituating the organism to absorbing entire bacilli which have been injected subcutaneously and by injecting small quantities of them we shall not habituate the organism to absorbing more." Trudeau, in 1889, employing living bacilli, immunized birds against tuberculosis, and he later stated that the first encouragement he had came only when he began the use of living bacilli. In 1889 also Dixon of Philadelphia, working with the branching forms of tubercle bacilli, reported progress in artificial immunization. In 1885 Theobald Smith differentiated the human baciUus from the bovine baciUus and it was at once natural to attempt to vaccinate the cow against tubercu- losis by the inoculation of human baciUi — so repaying that animal the debt we owe for smallpox vaccination. Pearson and GiUiland reported such work in this country simul- taneously with von Behring and Koch in Germany. I have recently received from Theobald Smith and from GiUiland a summary of their respective work in the immunization of cattle to tuber- culosis by inoculating baciUi of human origin. Theobald Smith reports that human bacilli could be discovered in the organs of cows some years subsequent to inoculation, and he states that human bacilli cannot be employed to immunize cows against tubercu- losis if those animals are destined for future dairy life. Calmette recently informed me at the Rome Congress that he does not believe that any injected organism can destroy tubercle bacilli, and for this reason his attempts at the production of immunity have been via the digestive tract. Heymans' attempts have been most original. Heymans enclosed tubercle bacilli in collodion sacks and placed these within the animal's body so that the blood juices might act on the bacilli without infection taking place. In perfecting the tubercle bacillus as a parasite, nature has deter- mined that it must have access to and egress from the organism attacked, and that this germ must not be too readily destroyed as it has no life history apart from the diseased organism. Nature has, therefore, caused the bacillus to build for itself a pro- tective covering of wax which is a highly resistant substance. It can be estimated that at least one-third of each bacillus is composed of wax and fats. Our body cells have considerable difficulty in disposing of such wax, yet it has been observed that the lymphocyte blood cells con- tain a ferment — ^lipase — which can digest such wax. Researches of Bartel, Opie, Bengel, Marie and Fiessinger all point to the lymphocyte cell as the active antagonist in our bodies to the tubercle baciUus. GERALD BERTRAM "WEBB, M.D. 47 Bartel showed that the tubercle bacillus passing through a mucous membrane becomes weakened and when it passes to a lymph node it is still further weakened. This latter phase Bartel speaks of as a latent lymphoid stage, and is the stage which probably all children develop. As you know from the researches of von Pirquet and others with the skin tuberculin tests, practically all children by the age of puberty are infected with the germs of tuberculosis. Romer, by his recent work on sheep, indicates that such early infec- tion can be in part protective against further or future disease, so that we may perhaps interpret this early tubercle infection of childhood as nature's crude method of vaccination against tuberculosis. That it is not a safe method, however, is witnessed by the fact that large numbers of children succumb to the disease. Dr. Sachs has spoken most kindly and in encouraging terms of our attempts to study the problems of immunization against tuberculosis, and I will briefly relate how we have approached these studies and what we have accomplished. Dwellers in high altitudes have for long felt that they possessed a higher immunity against tuberculosis than dwellers in the lowlands. As you know, some two thousand years ago Galen advised consumptives to sojourn in the high mountains. For some decades certain blood changes have been observed at high altitudes, such as an increase in the red blood corpuscles and also an increase in the percentage of hemoglobin. It was our good fortune, however, to determine that the lymphocyte element of the blood, above referred to as being antagonistic to the tubercle bacillus, was increased in the circulating blood in the same ratio as the red corpuscle was increased.* At an elevation of 6,000 feet, such as Colorado Springs, this increase amounts to some 30 per cent. Another blood element, too little studied but an element which we have determined takes some part in immunity processes, the third cor- puscle of the blood or blood platelet, is also increased in the circulating blood at a high altitude. Successful vaccination of mankind against tuberculosis is a medical triumph long sought but still long distant. Unfortunately up to now no manner of inoculating the living tubercle bacillus has proven entirely safe. In general a vaccinating virus must be a virulent germ and should for a while grow in the tissues, if possible at the site of injection, thereby stimulating the production of antibodies by the host; but this growth of the virus should be invariably destroyed by the injected animal. Some years ago I watched Professor Barber, with a most original technic, isolate single bacteria. • It occurred to me at once that this process might be applied to the inoculation of animals, with first one * We have no-w another possible factor, observed by the Anglo-American Physiological Expedition to Pike's Peak three years ago, namely, the increased development of the lung cells which take np the manufacture of oxygen and throw it into the blood stream. 48 PRESENT STATUS OF IMMUNIZATION AGAINST TUBERCULOSIS bacillus, then two, and by gradually increasing the number we might succeed in rendering the animal immune. Our first attempts were made with anthrax bacilli and mice, but, as was shown later by Barber himself, with such a very virulent organ- ism and with such a small animal success could not be expected. Inject- ing small numbers of human bacilli in a similar manner into guinea pigs and monkeys, we obtained a measure of success in immunizing such animals. We found that 120 bacilli injected at a single dose, of the culture employed, were necessary to produce disease in a guinea pig, but that when we began the inoculation with very small numbers, cautiously increasing, hundreds of thousands of these bacilli could be injected without the production of tuberculous disease. A scientist who watched these experiments, himself dying of tubercu- losis, requested that his two children, aged nine months and three years respectively, should be submitted to a similar course of inoculation. After four years these two children remain well and are negative to the skin tuberculin test of von Pirquet. We were to discover, however, in our work that all strains of tubercle bacilli were not equally virulent and it had been our good fortune to be employing a strain not the most virulent. We have found various degrees in virulence of the tubercle bacillus by the employment of the Barber technic, and from some cultures we have determined that ten bacilli will infect a guinea pig when inoculated at a single initial dose. So far we have failed to immunize guinea pigs by inoculating them with first one bacillus, then two, four, six bacilli, etc., of such a culture. Lawrason Brown has reported similar experi- ences. We have studied thirteen different cultures up to date and have found the minimum lethal dose to vary from ten bacilli to thirty bacilli, to fifty bacilli, sixty bacilli, 100 bacilli and 120 bacilli, respec- tively. In view of this varying degree of virulence in cultures of the human tubercle bacillus, we have been led to investigate whether the addition of antagonistic elements, such as lymphocytes or blood platelets, might allow us to inoculate safely a minimum lethal dose of the most virulent tubercle bacilli. Sensitized vaccines — that is to say vaccines made by the addition to virulent bacteria of serum from an immune animal — have been con- sidered to call forth better protective response in some cases in the injected animal than the injection of the bacteria alone could procure. Baldwin, however, found that the addition of serum from an "immune" cow caused tubercle bacilli to become even more virulent to the guinea pigs he tested. It is known that tubercle baciUi injected into the peritoneal cavity of a tuberculous guinea pig become rapidly destroyed, and it has been supposed that the mononuclear or lymphocyte type of cells found here was possibly responsible for this destruction. GERALD BERTRAM WEBB, M.D. 49 We inoculated, therefore, a series of guinea pigs with, each 100 very- virulent tubercle bacilli, with the addition of a fluid rich in mononuclear cells derived from the peritoneal cavity of a tuberculous guinea pig. We added to this mixture in some experiments the serum of an immune pig, both heated and unheated, but again our experiments were unsuccessful and our pigs developed the disease we were attempting to protect them from. In working with the third corpuscles of the blood, or blood platelets, we ascertained the possible evidence that they either carried or supplied an immune body known as opsonin. We then conducted a series of experiments on guinea pigs, inoculat- ing them with a small lethal dose of tubercle bacilli (200) to which were added in some instances the blood platelets prepared from a nor- mal guinea pig, in other instances the blood platelets procured from a tuberculous guinea pig. Our results have, however, not been con- stant, although we have thought that the platelets possibly modified the resulting infection. Again we have attempted in monkeys and guinea pigs to produce immunity by injecting a small number (100-200) of tubercle bacilli subcutaneously, and at about the fourteenth day excising the result- ing local lesion. In every case we have failed, as by that time the infecting organisms had reached the nearest lymph nodes, or had pen- etrated even further. Remembering that nature produces much fibrosis in her healed areas of tuberculous infection, we first produced scars by cuts or burns on the limbs, and then injected our minute infecting doses with some difficulty into these scars. AU our attempts were fruitless, all animals becoming diseased. We are at present attempting experiments in which we are aiming at the production of a local lesion which can later be excised, and at the same time we are preventing the infection travelling to the regional lymph nodes and blood streams. The method promises well and the results will be reported later. Up to date, however, we only offer the conclusion that by the employ- ment of a culture which is not too virulent, as tested by the minimum lethal dose, we can procure by the inoculation of increasing numbers of tubercle bacilli some degree of immunity to tuberculosis. We know too that nature infects us with very small numbers of tubercle bacilli, possibly less than ten, and it, therefore, suggests itself that by experimentation with such minute dosage of tubercle bacilli we may sometime achieve our goal of the safe production of immunity against tuberculosis. As Pasteur has so well said, "We must repeat again our experiments. The chief point to remember is to persevere." ETIOLOGY AND MORBID ANATOMY OF BONE AND JOINT TUBERCULOSIS By Charles M. Jacobs, M.D. CHICAGO The manifestations of tuberculosis in the human being are the result of infection by either the bovine or human tubercle bacillus. The relationship of these two types has been the subject of much investi- gation. In 1911 the British Commission, after an investigation lasting ten years, and at an expense of seventy-six thousand pounds, reported that three groups of tubercle bacilli can be isolated in the tuberculous lesions in man. Group One has all the characteristics of the bovine type. Group Two of the human type, and Group Three has some of the characteristics of both. Morphologically bovine and human tubercle bacilli cannot be differentiated, but they are regarded as different types of the same organism. They differ in their cultural characteristics and in their power of producing disease in different animals. The bovine tubercle bacillus is virulent to rabbits in five or six weeks after a generalized tuberculosis has occurred, whereas the human tubercle bacillus pro- duces a tuberculous lesion in the lungs and kidneys, which rarely causes death. The Commission further reported that a very large percentage of the surgical tuberculosis was due to bovine tubercle bacilli and that they rarely produce pulmonary tuberculosis. Various investigators have verified the findings of the Commission. One investigator believes in a transitional type of tubercle bacillus, where transformation from the bovine to the human tubercle can take place. Fraser, an able assistant of Stiles, studied the type of tubercle bacilli in seventy cases of bone and joint tuberculosis in children. The tuber- culous material obtained after operation was injected into animals, and after six weeks the animals were killed. The differentiation of the organism was based upon five tests. In forty-one of the cases the bovine tubercle was found; in twenty-six instances the human tubercle was found, and in three instances the mixed type. He investigated the source of milk supply — whether the child had been taking human or cow's milk. In nursing infants the human tubercle bacilli were found in nineteen instances and the bovine bacilli in four; while in children who had been drinking cow's milk, the bovine tubercle were found in thirty-seven instances and the human tubercle bacilli in seven. The family history was next investigated and he found in twenty-one instances that there had been pulmonary tuberculosis in the immediate family in which the child lived; the human tubercle bacilli were found in fifteen instances and the bovine tubercle bacilli in six instances. He 50 CHAELES M. JACOBS, M.D. 51 found that the age was limited to 12 years and under, which he divided into three groups. Group One was of children under 3 years of age; Group Two from 3 to 6 years; Group Three from 6 to 12 years. He found in Group One twenty-three instances of bovine tubercle bacillus, and in five the human tubercle bacillus. In the second group he found the bovine tubercle bacillus in nine and human tubercle bacillus in ten ; in the third group, the bovine tubercle bacilli in nine and the human tubercle bacilli in eleven instances: thereby indicating that the older the child the more often was the human tubercle bacillus found. It may be of interest to state that in a series of two hundred and three cases of bone and joint tuberculosis treated by us at the Home for Crippled Children, the age was 12 years and under. Statistics from these will give a good idea of the age at which bone and joint tuberculosis is most frequently seen. Age, Years Number of Cases 1 to 3 85 4 to 6 68 7 to 9 34 10 to 12 16 Total 203 Investigation showed that in thirty-one instances there was a history of pulmonary tuberculosis in sixteen fathers, eleven mothers, three brothers and one grandfather. In two children, 2 years of age, bone tuberculosis developed within six months after the mothers had died of pulmonary tuberculosis. There can be no doubt that the primary focus of infection in bone and joint tuberculosis is in the lymphatic glands — particularly the cervical, mesenteric and bronchial. The portals of entry of the tubercle bacilli are the tonsils, oral and nasopharyngeal cavities, the digestive and respiratory tracts. As a result of the caseation and destruction of the glands mentioned, the bacilli sometimes gain access to the small veins connected with them and are probably carried to the right side of the heart, then through the systemic circulation and distributed to various parts of the body. Very frequently they may be destroyed by the proliferating endothelial ceUs as weU as by the connective tissue cells and leucocytes, and if the resisting power of the child is enfeebled the bacilli take hold and a definite tuberculous lesion is the result. Various investigators have attempted to show the type of bacilli contained in these glands. One investigator inoculated guinea pigs with macerated cervical and mesenteric glands from one hundred and thirty-four children who had died. In fifty-two of the children a tuberculous process had been found at autopsy — in twenty-eight it was the cause of death. Forty- six of the guinea pigs reacted to the injection of both the cervical and mesenteric glands. The type of organism was studied — forty-five were of the human type, three the bovine, one the mixed type and three could not be determined. 52 BONE AND JOINT TUBERCULOSIS Mitchell investigated seventy-two unselected eases of tuberculous cer- vical lymph nodes in children. In 90 per cent, of the cases the bovine bacillus was found and in 10 per cent, the human bacillus. From these various investigations, what conclusions can be drawn? 1. Bovine tubercle bacilli can no longer be considered a negligible factor in the production of bone and joint tuberculosis in children. The medium of infection is principally by drinking infected milk. 2. Human tubercle bacilli are secondary to bovine tubercle bacilli in the production of bone and joint disease. Another important question is: Just where in the bones and joints does the disease begin? I might start out with the primary statement that up to the period of ossification we never have primary tuberculosis in the epiphysis. Why? Because the epiphysis, being cartilaginous, is never primarily attacked by tuberculosis. In adults the tuberculous focus is situated in the epiphysis and less frequently in the synovial membrane, whereas in children it is situated in the diaphysis and less frequently in the synovial membrane. While joint tuberculosis may manifest itself as a primary synovial disease, it is thought that it is more frequently the result of invasion from an osseous focus. Stiles believes that the localization of the disease is accounted for by the distribution of the three systems of intraosseal vessels — the diaphyseal or nutrient, the metaphyseal and the epiphyseal arteries, whose ultimate branches anastomose in the region of the metaphyses of bone ; that by whichever route the bacillus or embolus finds its way into the bone, in this last situation, it is most likely to be arrested. The cir- culation being slow at this point is another circumstance which makes this a favorable site for bacilli. It is a matter of accident, he thinks, whether the disease begins in the bone or in the synovial membrane, as the blood supply is the same — the metaphyseal and epiphyseal arteries enter the bone at the ligamentous attachments. I have felt very partial to Ely's theory, that the tubercle bacilli affect certain kinds of tissue, those containing lymphoid and epiphelial cells — therefore, the bacilli have a predilection for red marrow and synovia; that other tissues — such as ligaments, yellow marrow, muscles, etc., are immune. His theory seems plausible when we consider the structure of bone. We know that cancellous tissue is found in the ribs, vertebrae, sterum, cranial diploe, in the short bones, in the shaft of long bones in children and in the epiphysis in adults. We also know that wherever cancellous tissue exists in bone the marrow is red and that where yellow marrow exists there is no cancellous tissue. If, therefore, Ely's theory is correct, then it seems to explain why tuberculosis occurs in the short bones, in the diaphysis of bone in the child and in the epiphysis in the adult. At the lajst meeting of the Orthopedic Section of the American Medi- CHARLES M. JACOBS, M.D. 53 cal Association, Fraser advanced the theory that the pathologic process of bone began in the marrow, but experimentally it was difficult to infect the bone unless the marrow had first been made to undergo a fibro-myxomatous degeneration; that such a degeneration might result from an endarteritis of nutrient vessels or a tuberculous infection from a neighboring joint. He illustrated by lantern slides that a beginning tuberculous infection is a chronic endarteritis in a nutrient vessel. NON-OPERATIVE TREATMENT OF TUBERCULOSIS OF BONES AND JOINTS By John L. Porter, M.D. CHICAGO A long time before the operative surgeons had progressed far enough to operate upon tuberculosis of the bones and joints with any assurance, and I thirtk long before the early etiology and pathology were well under- stood, two facts which have had great influence upon the treatment of the disease had been well recognized. The first was that tuberculosis, or so-caUed scrofula of the bone and joints, was a self-limited disease. The second was that it always resulted in deformity. Recognizing those two facts, the early orthopedic surgeons formu- lated a method of treatment of tuberculous bones and joints which aimed to assist Nature to overcome the disease and to prevent, as far as possible, the development of the deformity. That method of treat- ment was, among other things, an important factor in establishing ortho- pedic surgery, in its pioneer days, upon a solid foundation and we are recognizing more than ever today that the treatment of tuberculosis of bones and joints is becoming more mechanical and less operative, in so far as the cure of tuberculous infection and the treatment of the deform- ity is concerned. Of course, conditions do arise in the clinical progress of tuberculous joints which demand operative interference, and the most beneficial mechanical treatment may have to be preceded by operative measures before it can be carried out. But the end and aim of all treatment of a tuberculous joint, without complication, is to put the joint into the best possible position for future use, immobilize it, relieve it from fric- tion and assist Nature in every way toward a spontaneous recovery. The method of immobilizing a tuberculous joint, preventing it from functioning and preventing the development of deformity, will depend upon the location and extent of the disease and the personal preference of the surgeon. It makes little difference what the individual method is, so long as it is thorough, efficient and continued for a sufficient length of time. "While a tuberculosis of the spine may be extensive enough to, demand prolonged recumbency in bed, it is evident that disease of the knee or shoulder might be treated equally well by some mechanical measures which would permit the patient to be up and about. Although such treatment may, and often does, require from two to five years, or even longer, the time element, in a child, is of little import- ance when a good functional result is considered — and a very large percentage of these cases do secure just that result. While early operation and complete removal of a tuberculous focus in or about a joint, is, theoretically, a much to be desired performance, we have learned by long and bitter experience that practically it is 54 JOHN L. POKTER, M.D. 55 impossible in a very large percentage of these cases. For we are not endowed with microscopic eyes and it is exceedingly difficult to remove all of a tuberculous focus. Such an operation almost invariably leaves the patient with a stiff joint and frequently with discharging sinuses which have to be dressed for years. Moreover, such operations, espe- cially in the young child, interfere with the growth and development of the bones involved and, at the end of five years, when the ultimate result of the operation is fully evident, he is no better off and frequently worse than he would have been had he spent that five years in allowing the joint to recover spontaneously under efficient mechanical treatment. Tuberculosis, in some joints, has a tendency to recover much more promptly than in others. For instance, I have frequently seen tuber- culosis of the cervical spine and tarsus in children make a complete recovery in a year, with efficient immobilization. As I said before, the method of immobilization is of little importance, so long as it is effi- cient and continuous. Many years ago surgeons relied upon braces and splints of metal and leather. Many of these were devised to per- mit of the use of traction, with the idea of separating the joint sur- faces and preventing friction and muscular spasm. Some forty years ago, the use of plaster of Paris was made popular by Dr. Lewis A. Sayre, of New York, and since then it has been extensively used and is today the chief reliance of many orthopedic surgeons, especially during the painful and progressive stage of the disease. Its great advantage is that it is efficient, comfortable and cannot be tampered with by the patient or family, and, if renewed sufficiently often to carefully observe the joint and care for the skin, it is very satisfactory for the first six months. Later, it should be supplanted by braces or splints which can be removed at short intervals and permit greater freedom to the muscles. When I was in Liverpool I was much surprised to see Mr. Robert Jones, the busiest and most capable orthopedic surgeon in Great Britain, treating hundreds of tuberculous joints without a pound of plaster of Paris, but he is especially skillful in devising and applying mechanical splints for tuberculous joints of all kinds, and he apparently secures as good results as anyone. Before plaster of Paris or any other immob- ilizing apparatus is applied to a tuberculous joint, the muscle spasm which is so characteristic of the disease is frequently so troublesome and the resulting pain so distressing that it is necessary to put the patient to bed and apply traction with a weight and pulley or some mechan- ical device, until the spasm and pain are relieved and the deformity, if any, is corrected, before applying mechanical apparatus. I have said little about tuberculosis of the joints in adults, but it is undoubtedly a fact that they require a longer time to recover and operative interference is indicated more frequently and earlier in the disease than in children, because the time element to a wage earner is of paramount importance, and if he can be enabled to get about, even with a perfectly stiff joint or a short leg, or even with an artificial foot, more quickly by operation 56 TUBERCULOSIS OF BONES AND JOINTS than by mechanical treatment, the operation should be done. But in children we see tuberculous joints recover from extensive disease with a surprising degree of motion, and even a little is oftentimes of great advantage. I have been particularly impressed with the great advan- tage of treating these cases in institutions which are properly equipped not only for the most efficient surgical and mechanical procedures but also for the most modern, hygienic-diatetic treatment. The most ideal place for these cases is where they can be given careful nursing and medical supervision by attendants who are properly trained; where those that are confined to bed can be taken out-of-doors; where the ambulatory patients can be permitted to rest and play in the fresh air, and where all can be given fresh milk, fresh eggs, fresh vegetables and fresh air in unlimited quantities. To that end, I hope that every tuberculosis sanitarium will eventually broaden its scope and be pro- vided with the necessary equipment to admit cases of tuberculous bones and joints, as well as tuberculosis of other organs. "We have hospitals for the special treatment of the crippled and deformed, and most of our general hospitals have wards for the treatment of such patients, but unfortunately they are practically all located in the city — most of them in the busiest parts of the city, where land is expensive and the out-of-door's freedom which is so beneficial to these patients is prac- tically nil or very limited. I can conceive of no one step which would be of so much benefit to the large number of poor patients afflicted with tuberculous bones and joints as the establishment of facilities for their proper treatment in country sanatoria. SURGICAL TREATMENT OF TUBERCULOSIS OF BONES AND JOINTS By Edwin W. Rterson, M.D. CHICAGO This is not a competitive debate, and neither Dr. Porter nor myself must be understood as advocating either operative or non-operative treatment exclusively. It is unquestionably true, and it must be distinctly recognized, that most cases of joint tuberculosis in children will get well by mechanical non-operative treatment, and the more cases we can cure by non- operative treatment the better. It is, however, becoming increasingly evident that in adult joint tuberculosis, non-operative treatment is not apt to be successful. It is becoming increasingly evident that the non- operative treatment of joint tuberculosis, even in children, requires a very great deal of time and a very great deal of care, and for these two reasons it is in many cases impossible for a child to get the proper treatment. In some cases it simply cannot be done. There are very many cases where from two to six years of surgical orthopedic treat- ment cannot be properly carried out in an individual case. Is there anything that we can do to help out a child, who, for instance, has a tuberculous spine and who cannot afford to pay $35 or $40 necessary for a brace and the necessary money each year to have the brace kept in repair and to do it for years, as the child grows? I believe that there is, — the operations for making an artificial anky- losis of the spine, which have been now for three years under very care- ful observation. We have done a large number of these operations in this city, and while it is too early to make any absolutely definite or positive statements about the results, it is safe to say that many cases have been apparently cured by them. In brief, it is a method of taking a piece of bone from the tibia with a saw and sewing it into a groove made by splitting the spinous processes of the vertebrae. This makes for us a splint and brace which apparently is better than any mechanical appliance which most of us can apply. Apparently children get well quicker with a splint of bone placed in the spine than they do with a brace. I say apparently, because although personally we only have in my clinics thirty-eight cases to report upon, yet many of them have apparently been cured in six months, and are today running about with- out any brace. Most of them seem perfectly well and have been made so with a minimum of danger and with a very slight operative risk. If such results can be made the rule, if we can count on getting such results in even a small majority of cases with only the small amount of risk that accompanies even minor operations, I think that if I had a child of my own with a tuberculous spine, I should have the operation done, rather than the wearing of the ordinary external brace for four or five years. 57 58 TUBERCULOSIS OF BONES AND JOINTS I want to speak of the treatment of the tuberculous joints in adults because to my mind it is radically different from the treatment in children. In tuberculous joint disease, we do not get cures by mechan- ical treatment alone in the enormous majority of cases. Personally, I have been doing orthopedic work for sixteen or more years, and I have not seen an adult with a tuberculous hip or a tuberculous knee get well without operation. I believe I have seen a tuberculous spine get well, but time enough has not really elapsed to show whether these adult cases are well or not. The very pertinent question comes up : " When is an adult not an adult ; when is a child not a child ? ' ' And that is what we cannot pos- sibly state, except arbitrarily. In looking over my series of cases I have failed to find any child over 16 years who has gotten well from hip or joint tuberculosis, really well, I mean, without operation. The right way to treat an adult tuberculous joint is to make that joint stiff and solid, just as soon as possible, because an adult joint will not get well from joint tuberculosis with a useful range of motion in the vast majority of cases. The best way to hold an adult tuberculous joint still is to make a bony ankylosis in a favorable position. It can be done very readily in the hip, by the method of Albee, of New York, who has devised an excellent operation which I have successfully done in several cases. In the knee joint it is extremely easy and safe to make an anky- losis and in an adult tuberculous knee the quicker you make an anky- losis the better, just as in the hip. You do not need to try to curette it out or scrape it out, because no surgeon can remove all the tuber- culous material that is in the joint. In the case of ankle-joint tuberculosis, I am obliged to take a very radical position, because I have had a large number of ankle joint tuber- culosis cases to treat in adults. Nearly all of these have had abscesses and sinuses, and all of them belonged to the working classes, where time and money were lacking. Most of them came to me after years of con- servative treatment, with the disease steadily growing worse, and I advised and performed amputation, with the most satisfactory results. The other operative methods which may be necessary in complications, such as paralysis, etc., I will not enter into at all. I will simply say that there is no one treatment for all kinds or all individuals afflicted with joint tuberculosis. "We simply have to do the best thing we can for the patient, according to our judgment. If you cannot cure the disease in any other way, amputate as soon as you can. Many adult cases are treated conservatively for too long a time. You cannot ampu- tate a spine, of course, but you can amputate legs. DISCUSSION Dr. John Ridlon, Chicag'O : I am fully in accord with what has been said by Dr. Jacobs and Dr. Porter, but I must oppose much that has been said by Dr. Ryerson. DISCUSSION 59 It should be remembered that patients suffering from tuberculous joints are also suffering from the disease — tuberculosis — and that any cure or apparent cure of the local manifestation in the joint is, as a rule, only temporary, unless the patient has also been cured of his disease — tuberculosis. Many years ago Wright, of Manchester, England, thought he could cure early joint tuberculosis by extensive excisions of the diseased joints, but it was found that the disease returned in the majority of cases, no matter how thorough the operation may have been. Then Battle, of London, demonstrated that excised tuberculous joints required a longer period of immobilization, after the excision, to complete the cure than did joints that had not been excised. At the present time, the advanced operators, like Dr. Ryerson, do not attempt to remove all the diseased bone when operating to immob- ilize these joints. Indeed some think that the less bone removed, the better. Doubtless this is so; and that we may hope that the time will soon come, as it has already come in operations on tuberculous spines, when no bone is removed at all. In speaking of Albee's operations to immobilize tuberculous spines and joints. Dr. Ryerson, quite unintentionally I think, used a very felicitous expression. He spoke of "Dr. Albee's fictitious mind." I would hardly go as far as that, but would say "fictitious theories." I am sure Dr. Ryerson 's impatience to gain quick results is responsible for his never having seen tuberculosis of the ankle recover without opera- tion. I have seen tuberculosis of the ankle with five sinuses recover with- out deformity and with good motion, having had no treatment of any kind whatever. I believe that operations should be done on tuberculous joints only as a life-saving measure. Never in thirty-six years of active work have I seen a tuberculous ankle that required operation; and never but one knee and one hip. As to tuberculosis in adult patients, my experience again differs from the opinion expressed by Dr. Ryerson. I am sure that adult joint tuberculosis recovers quite as promptly and quite as perfectly, under non-operative treatment, as does the disease in children. He admits having seen some perfect results in spinal tuberculosis. I have exhibited such cases at meetings where he has been present, and I shall have great pleasure in showing him similar results in hip, knees and ankles. It seems to me to be a great mistake at a meeting of this kind, where many laymen are present, to let the impression go uncontradicted that the only way to treat tuberculosis of the joints is to destroy them by a bloody and dangerous operation. NON-TUBERCULOUS LESIONS OCCURRING IN TUBERCULOSIS By Joseph Zeisler, M.D. CHICAGO I cannot very well see why a patient suffering from generalized tuberculosis should not be affected by any of the well-known skin dis- eases. You are all aware of the fact that a patient who has pulmonary tuberculosis is inclined to excessive perspiration and conditions result- ing from this are frequently found in such patients. I have in mind one condition which might be pointed out and which is known by the name of Pityriasis Versicolor, an affection of the skin appearing in patches on the chest or back; light brown or sometimes a little darker patches which can be easily scraped off and show, under the microscope, vegetable fungi. But even in the case of Tinea Versicolor, you will find it often enough in people who present not even a suspicion of tuber- culosis, but who perspire freely. The subject of tuberculosis of the skin is one of comparatively recent date. Looking back a little over thirty years we find that only one form of tuberculosis was recognized, but since that time the sub- ject has assumed enormous proportions, and from year to year its importance has increased. This is due very much to the fact that finer methods of diagnosis have been introduced. When we depended chiefly upon the verification of tubercle bacilli in pathologic lesions, when we recognized forms of tuberculosis only in dermatoses in which this organism could be easily and assuredly detected, the list was not very large; but since the finer methods of Pirquet, Calmette and Moro and particularly the injection of tuberculin as a method of reac- tion have been introduced, it has been found that many diseases of the skin were intimately related to tuberculosis in which this previously had not even been suspected. I do not know whether my esteemed colleague, who is to follow me, will consider that I am trespassing upon his ground when I under- take to say a few words about certain affections in tuberculosis which are not classed as tuberculosis proper but as so-called tuberculides; but I am sure his phase of the subject is sufficiently large. By tuberculides we mean cutaneous affections in which Koch's bacillus is not found, as a rule, but which react positively against one or another of the tests which I have just mentioned. To cite one illustrious example, a subject in regard to which a con- siderable change of opinion has taken place, particularly within the last few years, I would mention Lupus Erythematosus. Lupus Vulgaris, as has been known for many years, is a true form of tuberculosis, a standpoint which was not held generally, even in 1884, when Kaposi denied stoutly that Lupus Vulgaris had any connection with tuber- 60 JOSEPH ZEISLER, M.D. 61 culosis. As regards Lupus Erythematosus, a fight has been waging, on and off, for many years ; but today some of the most conservative der- matologists are strongly inclined to class it as one of the tuberculides, because many of the cases react against the injection of tuberculin positively. Another example is a disease of the skin, known as Lichen Scrofu- losorum, first described by Hebra, who meant to convey the idea that it was found in scrofulous subjects but was not itself a form of tuberculosis. For years and years the position of this disease was uncertain, as tubercle bacilli were rarely found in the lesions, but in more recent years the reaction of patients affected by this disease against tuberculin injections has been so frequently positive that today Lichen Scrofulosorum is classed with the tuberculides. I would also remind you of Acne Varioliformis, called by this name because its lesions resemble those of variola or smallpox. It is a some- what unusual disease, occurring in the form of pustules tending to necro- sis upon the forehead, the scalp, the nose and occasionally upon the back; a disease which has also been called acne necrotica by Boeck, of Christiania. This dermatosis has been gradually taken over into the field of tuberculosis. Another disease, of somewhat obscure nature, and rather rare, has been described as "Erytheme indure des scrophideux" by Bazin. Its nature has been misunderstood for many years. Not so very long ago, in 1896, at the London International Congress, when instances of this disease were demonstrated, a famous dermatologist would pass by and, with a sweep of the hand, say "mercurial plaster," indicating that he considered them gummatous syphilides. This Erythema Induratum is today classed with tuberculosis. Another disease, which was known for many years and was described first by Hebra under the name of Acne Cachecticorum, is practically a generalized form of acne consisting of papulonecrotic lesions, in subjects who are run down, and is today well recognized as one of the tuber- culides. These patients react distinctly and positively against tuber- culin injection. Some other more unusual diseases which Barthelemy described under the name of FoUiclis and Acnitis, show lesions in the first instance upon the surface in general; in the second, especially in the face. The nature of these diseases has not been thoroughly understood until recent years, when their relation to tuberculosis has been established. There is no doubt that Eczema often occurs in tuberculous patients. We know, in fact, a distinct form of Eczema in infants, which we consider as scrofulous eczema, and I have usually been able to identify it, not only by an enlargement of the glands but also by its peculiar location, around the nostrils, corners of the mouth, ears, etc. This distribu- tion alone should arouse your suspicions as to the cause being scrofu- losis, which, as you know, is a form of tuberculosis in children, patho- 62 TUBERCULOUS LESIONS logically identical with tuberculosis, yet which I still believe it is wise, from a clinical point of view, to separate from tuberculosis in general, on account of its benign character. That other diseases of the skin may and do occur in tuberculous sub- jects, we have no special reason to doubt. TUBERCULOUS LESIONS By Oliver S. Ormsby, M.D. CHICAGO The subject of tuberculosis of the skin is a large one. It is, there- fore, difficult even to outline it in a few minutes. There are two classes of disorders that must be discussed in this connection: the one in which the bacillus of tuberculosis is present in individual lesions; the other, which is produced by the toxins of the bacillus when the latter is in a distant focus. I shall limit what I have to say to a brief description of the disorders commonly acknowl- edged to be tuberculous and induced by the local action of the tubercle bacillus. Although we are all more or less familiar with the symptoms of these various disorders, I think it is proper to make a resume of them. The first and most important of the tuberculous disorders of the skin is lupus vulgaris. For many years it was described as an entity, and not connected with tuberculosis, but for some time now it has been acccepted by all as being of tuberculous origin. The disease usually occurs in children, at least it commonly begins in childhood, and attacks the face, about the nose more often than other parts. Occa- sionally the disorder begins in adult life, and very often extends to adult life from childhood. Other areas that may be involved are the neck, ears, extremities, and various parts of the trunk. Many names have been given to the various manifestations of this disease. A patch of lupus presents the following features : It begins as a small, brown- ish-red, slightly elevated spot in the skin, which soon becomes covered with a scale. This gradually spreads peripherally until an area the size of a dime or silver quarter, or larger, becomes involved. Under pres- sure with a glass (diascope), apple- jelly-brown nodules may be seen throughout the patch. These are soft in consistency and are character- istic of the disease. The disease spreads very slowly, and requires a number of years to produce even a moderate-sized patch, as a rule. In certain cases, the infiltration spreads as an even brown discoloration, in place of the small nodules before mentioned. At times, on the neck or OLIVER S. ORMSBT, M.D. 63 trunk or other situations, the disease spreads peripherially and heals in the center, producing a serpiginous configuration in which syphilis is closely simulated. In certain cases of lupus a marked connective-tissue new-growth occurs, producing the hypertrophic variety; in others, changes occur which induce marked deformity; in still others, by ab- sorption of tissue about the end of the nose, a deformity is produced suggesting the parrot's beak. The lupus patch may become the seat of other changes, producing varieties known as lupus verrucosus, and lupus papillomatosus. Other descriptive terms, such as lupus nodosus, oedema- tosus, tumidus, elephantiasicus, etc., are applied to those cases assuming these forms. In this country, ulceration is not as frequent as it is abroad, and while the name, lupus, suggests an ulcer, we more often see the non- ulcerated types before mentioned. The common conception, therefore, that lupus means an open ulcer often leads to the error of classing in this category the superficial epitheliomata or skin cancers that occur in people around and past 40 years of age. The brownish-red, scaly patch of lupus, with the soft nodules shown under the diascope, is very different from the hard nodules or ulcerated area surrounded by a pearly margin which is found in epithelioma; and is also quite different from the circinate, indurated nodules of syphilis, which only remain in one area a short time, undergo ulceration, and heal, developing in a new situation, or rather, situations. At times a deeply-situated, ulcerated lupus of the nose may be strongly simulated by a gummatous syphilide of the same area. The rapidity of the destructive process in the latter, as well as the probable bone involvement, makes the differentiation between the two. In a second variety, there occur warty lesions, classified as tubercu- losis verrucosa cutis. This variety always follows inoculation. There are two forms described — one, the anatomical tubercle or post-mortem wart, which usually occurs on the hands of people handling dead bodies. The lesions in this variety are, therefore, about the backs of the fingers and dorsal surface of the hands. The lesion begins as a small papulo- pustule, which spreads peripherally and soon becomes verrucous or warty. It is only moderately elevated and usually comparatively dry and very slightly inflammatory. Marked exceptions, however, to this rule occur. In some cases a reddish halo surrounds the lesion, but the miliary abscesses so common to blastomycosis are rarely seen here. These lesions usually develop to the size of a dime or a little larger, and then remain stationary. A second more extensive variety, described by Riehl and Paltauf, occurs not only on the backs of the hands but also on other parts of the body, including the forearm, thighs and trunk. The patches in these cases are larger than those just described, are more papillomatous, and are apt to have a greater amount of purulent discharge. They present, however, the same verrucous appearance, and are microscopically iden- tical. 64 TUBERCULOUS LESIONS Verrucous tuberculosis is found frequently in certain mining dis- tricts where pulmonary tuberculosis is common, and is said to be induced by the miners wiping their mouths with the backs of their hands after having expectorated discharges loaded with the bacilli. Cases are on record of this variety being produced by the bovine tubercle bacillus, such a group having been recorded by Lassar. The progress of these cases is slow and the subjective symptoms are practically nil. As the disease spreads peripherally, healing occurs in the center, result- ing in a certain amount of scar formation. A third variety is that termed scrofuloderma. In this variety, infection of the skin with the bacillus of tuberculosis always occurs by direct contiguity with some structure beneath the skin. The com- monest sources for this infection are the glands about the neck, the various joints, and some bones. There is a variety which occurs first as subcutaneous tuberculous gummata which, by extension upward, sec- ondarily involve the skin, producing the same type of lesion as the others. The ulcers that occcur in the scrofulodermata are irregular in outline, have soft, often undermined edges, their floors frequently per- forated by sinuses leading to structures beneath, and their secretion is usually a thin, muco-purulent or, occasionally, hemorrhagic discharge. Not infrequently bridges of tissue extend across the ulcer, which have not been destroyed. Occasionally a tuberculous lupus nodule may be found about the edge of the ulcer, showing the identity of the etiology of the two conditions. A fourth variety is that form which usually occurs about the muco- cutaneous orifices, and is represented by ulcers. It is sometimes called orificial tuberculosis, or miliary tuberculosis of the sMn, or simply tuberculous ulcers. In these cases, the lesion begins as a small nodule which breaks down rapidly, producing an ill-kept ulcer with soft, irreg- ular margins and unhealthy floor, one which gradually spreads and rarely heals. These ulcers occur always in the subjects of tuberculosis — in the throat, the intestinal tract, or other internal organs having con- nection with the surface by way of mucous membranes. As a rule they are small, but occasionally by peripheral spreading and coalesence of several lesions large surfaces may be covered. In addition to the muco- cutaneous orifices, the lesions may occur about the nose and face and other regions. In addition to the classical varieties mentioned above, it is important for us to recognize that several other forms of tuberculosis occur. There is a disseminated lupus which occurs in patches presenting the usual apple-jelly, brown lupus nodule, pretty generally distributed about the body, frequently following an attack of measles. Many such cases are recorded, particularly in England. Certain cases, also, of erythema induratum of Bazin are undoubtedly tuberculous; that is, they are induced by the bacillus of tuberculosis in the lesion. Others of these cases are unquestionably tuberculides. Finally, some of these eases can be placed in the group of sarcoides. WILLIAM ALLEN PUSET, M.D. ^^^Qo There are several other rare forms which hardly need be described today. In the microscopic study of tuberculosis of the skin, it is found that the baciUi occur in very small numbers in lupus. They are some- what more abundant in the verrucous varieties and also in scrofulo- derma, and are quite abundant in the orrficial variety. On the other hand, giant-cell formation is common in lupus, while the so-called cheesy degeneration common to internal tuberculosis is found only in the mil- iary or orificial variety in the skin. The best method for finding the bacilli is by the use of antiformin. In this way the tissue is dissolved and the bacilli are left in the solution. Recent findings which deserve further investigation and which may solve some of the problems relative to the apparent scarcity of the baciUi in these lesions concern the granules described by Much. These granules, which are of different forms, have been found by this observer, as weU as by several others, in aU tuberculous conditions, and occur either in association with or independently of the acid-fast baciUi. They are gram-positive, and have been found in some of the conditions hereto- fore described as tuberculides. For example, in lupus %nilgaris a very few acid-fast bacilli may be found, with a much greater number of the gram-positive granules of Much. By the antiformin method this has been done several times, and in certain diseases, such as lupus erythema- tosus, in which the bacillus of tuberculosis is not found, these granules have been found. The question is still open, but it is worth the atten- tion of those interested in tuberculosis, as these granules may be a form of the tubercle bacillus. Neither the true tuberculosis of the skin nor the tuberculides are as common here as they are abroad, although during the course of a year a number are seen. However, we are all struck by the difference in the number of cases shown here and those shown in various parts of Europe. Men like Dr. Zeisler, whose early training was had in Europe, cannot help but note this difference. Notwithstanding this fact there are a sufficient number to warrant our attention and to demand, at least to a certain degree, a knowledge of their symptoms. TREATMENT OF CUTANEOUS TUBERCULOSIS By William Allen Pusey, M.D. CHICAGO ' From the standpoint of treatment, there are, speaking generally, two forms of tuberculosis of the skin: (1) True tuberculosis of the skin, usually occurring in the form of lupus \nilgaris; and (2) scrofulo- derma, in which the skin is involved secondarily as the result of an 66 TREATMENT OF CUTANEOUS TUBERCULOSIS underlyiiig focus of tuberculosis, usually a tuberculous gland or bony structure. This latter condition hardly belongs to us. Its treatment is usually surgical and is a question of the treatment of the primary deeper lesion of tuberculosis. I shall, therefore, leave scrofuloderma out of consideration and confine myself to the treatment of lupus. The treatment of lupus has been one of the unsatisfactory things in medicine. The reason is this: The lesions show an almost malignant tendency to spread and to recur. One tubercle develops after another, slowly and painlessly, but persistently, and do what we may in the way of chemical or mechanical destruction, the disease goes on with the formation of tubercles in new areas, or the development of tubercles in the scars of previous lesions, and so cases used to go on year after year, gradually producing deformity that, in the worst cases, was hideous. But to return to our point, we never knew when we were done with a case, because the disease was always recurring, after destructive measures and so the treatment was unending. We entered into a new era in the treatment of tuberculosis of the skin when Finsen discovered that the lesions could be destroyed by exposure, under certain conditions, to intense degrees of ultra violet light. The older methods had consisted of all sorts of mechanical and chemical destructive measures. This, of course, carried the disfigure- ment of the patients often further than the original disfigurement by the disease. In addition to relative permanency of results, the Finsen method of treatment with ultra violet light does not destroy the healthy tissue in which the tubercles are imbedded, so it does not add to the disfigure- ment; but, on the contrary, produces a relative improvement in the contour of the involved parts. There have been some improvements in technique in Finsen 's method and considerable improvement in apparatus, but no improvement in the principles involved; and Finsen 's method of treatment of lupus is vir- tually the last word on the subject. Radium and X-rays can be used in the same way. There are no essential differences in the results, except insofar as they are on the side of Finsen 's method with ultra violet light. The introduction of the principle of treating lupus by exposure to radiant energy of high actinic properties was the introduction of a new principle in the treatment of skin diseases ; and Finsen, who intro- duced this principle, was a real benefactor of the human race. In this country, where we have little squalor, lupus is uncommon and Finsen 's benefaction is not of such obvious importance, but in the densely popu- lated districts of Europe, with their poverty-stricken people, Finsen 's discovery has given an amount of relief to a horrible disease that makes the discovery stand out as one of the very important contributions to- therapeutics in the nineteenth century. TREATMENT OF CUTANEOUS TUBERCULOSIS 67 DISCUSSION Dr. Theodore B. Sachs: I would like to ask Dr. Zeisler to define, ia a brief way, the five or six conditions that he mentioned. Dr. Zeisler : I simply desired, in my remarks, to present the general scope of these affections, but would be very glad to supplement, in a very few words, these various forms. I have never had any difficulty in pronouncing the word cachectic, as some seem to have. As far as describing Acne Cachecticorum, it is really a peculiar disease of the skin, more or less generalized over the extremities and somewhat over the trunk, and consists of lesions which, in themselves, are very much like those in ordinary acne — namely, small pustules which in this case are somewhat flabby and show little tendency to heal, but tend to break down and so form scars. This is usually found in patients who are very badly run down. The condition which I mentioned as Acne Varioliformis is really one of the most characteristic diseases of the skin. It can easily be rec- ognized by its peculiar location. It generally occurs upon the fore- head, upon the skull, occasionally upon the nose and occasionally upon the back. The lesions run a course very much like that of variola or smallpox, except that a scab forms which sometimes remains for weeks or even months before it finally drops off and leaves a scar. This is not common here ; I have seen, in my thirty years of practice here, about a dozen cases of it. Lupus Erythematosus which I also mentioned, is a well-known form, probably known to all medical people here, — a disease which often has the appearance of a butterfly — that is, starting over the bridge of the nose and spreading over the cheeks in the form of two wings. Isolated patches occur upon the scalp and behind the ears, but very rarely upon the body. Another form, which I mentioned, namely Folliclis, consists of small papules, necrotic lesions, usually on the extremities, which have a tendency to break down and naturally leave scars. Question : Do you find any particular racial exhibition of these dis- eases, or, in other words, do these diseases occur in the colored race? Dr. Ormsby: I have no statistics relative to the proportion of cases which occur in the races, but that aU varieties of tuberculosis, as well as the tuberculides, do occur in the colored race there is no doubt. In fact, some of the most remarkable cases that have been used for illus- tration of these diseases have occurred in that race. Concerning the sus- ceptibility of the skin, I do not believe the problem has been worked out. Dr. Zeisler: The tendency in modern times has been very strong to generalize the treatment of all forms of tuberculosis. Of course, when we have an individual localized patch of lupus or other forms 68 TREATMENT OF CUTANEOUS TUBERCULOSIS of tuberculosis, intensified local treatment seems to suggest itself promptly; viz., excision, chemical destruction and phototherapy. The treatment by tuberculin is being frequently employed, and I have in mind one interesting case, which I managed about a year ago. It was a very remarkable case, — a young gentleman from Indiana, who for ten years had had all sorts of lesions, tending to appear on his body, particularly in the axillary, inguinal and gluteal regions. Opera- tion after operation was performed upon him ; all kind of vaccines were used, but a clear diagnosis was not made. When this case came under my observation, I immediately diagnosed it as Lichen Scrophulosorum. He was sent to the Michael Reese hospital. All kinds of tests were made in order to verify my diagnosis, but at first without result. After two days I received a telephone message from my son, who was an interne there at the time, saying, "Father, I congratulate you. We found tubercle bacilli in the discharge from the cutaneous abscesses." From then on I started to treat this patient by injections of tuberculin, beginning with a small amount and carrying it up to the point of tol- erance. Some surgical work was done by Dr. Willys Andrews, and the injections, combined with other measures, brought about a cure in this case in the course of six months. Treatment of this sort must be done in a careful manner, and I believe some preparations have become so reliable that today we may consider tuberculin as an important factor in the management of many forms of tuberculosis. THE LAEYNX IN THE EAELY STAGES OF PULMONAEY TUBERCULOSIS By Elmer L. Kenyon, M.D. CHICAGO It is safe to say that a meeting like this, devoted exclusively to the discussion of tuberculosis of the larynx, would never have been held, if it were not for pulmonary tuberculosis. For the question of tuber- culous laryngitis, exclusive of pulmonary tuberculosis, is so rare as to be an academic rather than a practical question. "While primary laryngeal tuberculosis is not at all impossible, and, according to observ- ers, has been demonstrated, yet the conditions under which it would be likely to be produced are so difficult of fulfillment, except through the conditions present in pulmonary tuberculosis, that it must occur as a primary disease only with extreme rarity. Laryngeal tuberculosis should be looked upon from both a scientific and a practical standpoint almost exclusively as a complication of pulmonary tuberculosis. One who watches the larynges of case after case of pulmonary tuber- culosis in the earlier stages becomes convinced of the great relative resistance of the larynx to tuberculous infection. One sees the larynx literally bathed in tuberculous infection day after day for weeks and months, without succumbing to the invader. But, on the other hand, while its resistance to tuberculous infection is much greater than is the resistance of pulmonary tissue, yet its resistance is remarkably less than that of the other structures in the upper air passages. The only pos- sible exception to this statement is the tonsil; but our knowledge of tuberculosis of the tonsil in early pulmonary tuberculosis is too slight for careful comparison. The study of the possible explanation for the yielding of this naturally resistant mucous membrane to tuberculous invasion, while a similar mucous membrane in the adjacent structures holds out against infection, is one of my purposes in this discussion. We may presume that the larynx starts out in pulmonary tubercu- losis as a normal structure; but the conditions are such that after a certain number of weeks the larynx is practically never a normal struc- ture. The continual wear and tear caused by the forcing of the abnor- mal secretion of the lungs through the larynx results, in practically every ease of pulmonary tuberculosis, after some weeks, in a larynx which is not normal. What are the abnormal conditions which we find in the larynx after a certain number of weeks of pulmonary tuberculosis? Hyperaemia of a dusky character is extremely common, affecting all parts, but most often the arytenoid region. Transient but persistent acute hyperaemia is common. In winter, such an acute hyperaemia is practically universal in patients who live out-of-doors in this climate ; it is probably protective in its effects. Roughening of the cords, with at times actual paresis, and 69 70 THE LARYNX, EST PULMONARY TUBERCULOSIS with resulting tendency to aphonia, is seen and is capable of complete recovery without local infection with tuberculosis. And, more than all of these, we find infiltration in the posterior upper parts of the larynx. This is variable in degree and affects particularly the inter arytenoid and the arytenoid region itself; the infiltration of the aryteno-epiglot- tic fold is comparatively rare. These infiltrations evidently follow a great deal of wear and tear in the larynx and occur in different pul- monary, or laryngeal, affections; in pulmonary tuberculosis they prob- ably never are wholly absent after a certain duration of the pulmonic disease. Considering now the engrafting of tuberculous infection in the larynx through local mucous membrane infection, what is the mechan- ism of the process ? Through the wear and tear resulting in the abnor- malities mentioned, one must suppose that the resistance of the epi- thelium to infection becomes impaired. The superficial cells are injured and possibly form a less thick layer of resistant tissue. In proportion as this injury becomes an actual abrasion is tuberculous infection to be feared. Indeed, it is safe to say that in the earlier stages of pul- monary tuberculosis, tuberculous infection from the lumen of the larynx does not occur, except through an actually injured mucous membrane. The irregularity of the laryngeal surface, by harboring secretion, undoubtedly encourages infection. But the fact is true, like- wise, of the mouth and nose, which are not so readily infected with tuber- culosis. Motion as a factor in disturbing the already abnormal mucous membrane is worthy of careful consideration. The motion of talking affects not only the larynx but also the soft palate and the tongue; and, moreover, the movement in the larynx from talking is not violent, and the edges of the vocal cords are not brought into contact roughly. While talking, in connection with the irregularity of the larynx and the abnormality of the mucous membrane, may well be looked upon as a factor in the injury of the mucous membrane, which results in tuber- culous infection, yet there occurs another form of motion in the larynx which probably is more important. I refer to cough. What occurs in the larynx when one coughs? With the quick inhalation the larynx is forcibly pulled downward by the extraneous down-pulling group of muscles and, as it were, braces itself for what is to follow. At once the cords strike forcibly together and hold firmly against the contrac- tion of the walls of the chest upon the accumulated air, forcing it against the resistant cords; then, instantly, the larynx violently opens and the air bursts through. This motion is not only more violent than the motion of talking, but it is commonly repeated over and over during each day. The cords not merely touch but they are driven firmly together and hold against a pressure from below; the mucous membrane of the edges of the cords are much more likely to be injured than they are from talking. Moreover, the movement of the larynx in the arytenoid region is much more violent than in talking. Here, where, as Dr. W. E. Cassel- ELMEB L. KENYON, M.D. 71 berry has well pointed out, the infiltration of the mucous membrane has resulted in diminishment of flexibility, cracks or other abrasions are very likely to result from violent and often repeated motion. One thought more. What is the function of the laryngologist in pul- monary tuberculosis? The function of the laryngologist is, to use a lo- cally popular phrase, to be "the watch dog of the larynx." The larynx should be watched as faithfully as the obstetrician watches the urine of his patient for albumen. It is the business of the laryngologist to know when the larynx is approaching a condition which puts it in imminent danger of tuberculous invasion. It is his business to know at the earliest possible moment when tuberculosis has actually taken root in the larynx. If it be true that local treatment of the larynx, after weeks of infection, results in benefit to the larynx in tuberculosis, then it is more true that local treatment of the larynx may result in healing the roughened or cracked mucous membrane before the tuber- culosis has become engrafted. If it be true that local treatment, after weeks of laryngeal tuberculosis, is capable of improving the tubercu- losis of the larynx, then it is all the more capable of benefitting this form of tuberculosis when, through the close watching of the larynx, one is able to institute treatment at once, or very soon after tuber- culosis has become engrafted. One should watch the larynx in pul- monary tuberculosis, know what is going on, and when suspicious con- ditions arise take care of them and not wait until tuberculosis is established and extended. If careful consideration of the general and pulmonary condition of many patients is capable of enabling us to prevent pulmonary tuberculosis, or if it is desirable to diagnose pul- monary tuberculosis early, then it is likewise practicable and desirable in pulmonary tuberculosis, by keeping close watch of the larynx in individual cases, either to prevent the advent of the infection of the larynx with the tuberculous germ, or if engrafted, to make the diagnosis early and to institute treatment when treatment is most likely to succeed. I would, then, to conclude, emphasize two thoughts, — one concern- ing the probable especial bearing of cough on the infection of the larynx with tuberculosis in pulmonary tuberculosis; and, second, the need of routine watching of the larynx in every case of pulmonary tuberculosis. SYMPTOMS AND DIAGNOSIS OF LARYNGEAL TUBERCULOSIS By E. Fletcher Ingals, M. D. CHICAGO For the detection of the earliest manifestations of tuberculosis, it is important that the physician should be an expert diagnostician in dis- eases of the nose, the throat and the chest ; otherwise he is liable to error at the very time when his knowledge would be of the greatest service to the patient. Later in the disease, the well qualified general practitioner will only rarely find much difficulty in making a correct diagnosis; but even then there are some cases in which the evidence is very confusing, so that it may be difficult to decide between certain cases of simple chronic catarrhal infiammation, malignant disease, syphilis, lupus and tuberculosis. This statement applies largely to diseases of the upper air passages only, but it is also often true of the manifestations of disease of the lungs. The physician should begin his examination with a careful analysis of the history, including heredity, from the early childhood of the patient, for not infrequently the hereditary tendency or the effects of some previous disease may prove one of the vital factors in the evidence, and occasionally even peculiarities of absolutely healthy individuals must receive judicious consideration before a correct decision can be formed. I cannot too strongly insist upon these statements, but I will not take your time by going into detail. I will confine myself to the more salient features of the diagnosis. Having critically considered the history and subjective symptoms, the physician should address himself to a careful examination of the objective signs of departure from health, never forgetting normal vari- ations from the typically perfect form. As an illustration of the need of this latter precaution in diagnosis, I may mention one of the common errors made by those who specialize in diseases of the nose. In exam- ining the naris, they find a more or less prominent spur projecting from one side of the septum and many at once decide that it should be removed, totally ignoring the fact that such obstructions are present in 50 per cent, of the Caucasian race, and that in nearly all of these they have not the slightest effect upon the individual's health or happiness, if they are let alone. The early symptoms of tuberculous laryngitis are like those of an ordi- nary cold, which continue for several weeks, usually attended by hacking cough but with little or no expectoration. These symptoms may con- tinue for several months before they attract serious attention. Early there is sometimes a peculiar weakness of the voice and often the patient is hoarse. There is loss of strength and weight, hardly appre- 72 E. FLETCHER ENGALS, M.D. 73 ciable in the beginning, usually attended by some rapidity of pulse, and often by slight elevation of temperature in the afternoon, from one-half to one degree. As the disease progresses, the symptoms become more and more pro- nounced and the patient usually develops the symptoms of pulmonary tuberculosis. Emaciation occurs, the appetite is impaired and pro- gressive weakness occurs, cough is more frequent and productive, and, if ulceration takes place, pain in the larynx is generally experienced in swallowing, and tenderness may be present on palpation. In some advanced cases with extensive ulceration, the dysphagia becomes most distressing, often so great that the patient will gradually starve rather than eat; but the amount of pain depends largely upon the location of the ulcer. Sometimes a large ulcer may cause but little inconven- ience, while a small one located differently may be very painful. The pulse, in advanced cases, usually runs from 120 to 140 per minute and daily afternoon fever of two or three degrees is common; the skin is sallow, hot and dry, or at times, especially at night, bathed in profuse perspiration. In nearly all cases of laryngeal tuberculosis, superadded to the laryngeal symptoms are those of pulmonary tuberculosis, which gen- erally precedes the laryngeal trouble ; however, the latter may often be detected before the pulmonary signs have attracted any attention. In advanced cases, dyspnoea is often present, generally due to weakness and pulmonary involvement ; but in a small percentage of cases it results from swelling with obstruction of the glottis. When swelling of the upper part of the larynx prevents its closure during deglutition, fluids leak into the trachea and cause distressing spasms of cough. The tenacious secretion, during the later stages, often causes a very annoy- ing and sometimes painful cough that is frequently productive of vomiting and thus hastens the progressive emaciation and adynamia. Anaemia of the mucous membrane of the nasal cavities, but more especially that of the palate, is often one of the earliest signs of the disease. The larynx itself may be either pale or of a dull red color, but the congestion is very rarely of the bright color that characterizes acute and sometimes chronic catarrhal laryngitis, and it also differs from the dull red color found in most malignant affections of the organ. One very suggestive sign that marks the very beginning of a lim- ited number of cases of tuberculosis of the upper air passages is a peculiar thinness or atrophy of the laryngeal walls, which may appear not more than a third to half as thick as normal. This condition, when present and associated with the pallor already referred to, is almost pathognomonic. In some cases, a diffused dull congestion, not only of the cords but of the upper part of the larynx, coupled with diffused 74 SYMPTOMS AND DIAGNOSIS OF LARYNGEAL TUBEECULOSIS or local thickening of from 25 to 50 per cent, is one of the signs that appear during the first year. This is attended by sluggish movements of the cords which cause the hoarseness. Impaired mobility of the larynx, due to involvement of the muscles, associated with feeble voice and some hoarseness, sometimes appears to be one of the first evidences of tuberculous laryngitis, but the sign is not characteristic and must not be given weight, except as associated with other signs. During this early stage elimination of gastro-intestinal and renal disease and critical examination of the lungs, aided by the tuberculin test, are most important in reaching an accurate diagnosis. Later on pale dense swelling of the epiglottis and the characteristic pyriform swelling of one or both ary-epiglottic folds ; and the thickened posterior commissure, bathed in grayish mucus or a more yellowish muco-pus, are pathognomonic. The swollen parts occasionally appear much like oedema, but in nearly all cases the observer gets the impression of solidity of the parts. Only one of these parts may be swollen, but usually two or more are involved. With this condition ulceration is usually present. The ulcers are generally superficial, 1 to 2 mm. deep, with worm-eaten edges and irregular yellowish gray surfaces. The ulceration commonly begins on the venticular band and ere long involves the oppo- site side, the posterior commissure and the true cords. It is significant that in tuberculosis ulceration ordinarily begins at the lower part of the larynx, while in syphilis it is apt to start on the epiglottis. In a small percentage, tuberculous ulcers may be 3 or 4 nun. in depth, like specific ulcers; but I do not remember having seen any of them with the sharp or undermined edge so common in syph- ilis. Not infrequently there are tuberculomas of a cord or of the poste- rior commissure. These are apt to have an ulcerated surface. I have occasionally seen an acute tuberculous follicular inflammation of the epi- glottis, characterized by dull congestion and swelling, with several yel- lowish gray patches in appearance much like those of follicular tonsi- litis. This is usually attended by much pain and in my experience has commonly been followed by rapid superficial ulceration, spreading from point to point. The symptoms and signs I have mentioned will be sufficient to estab- lish the diagnosis in the great majority of cases, but there are very rare cases in which syphilis and tuberculosis are combined that will demand a most searching examination. In other cases, of comparative frequency, we must distinguish between chronic catarrhal laryngitis, syphilitic laryngitis, lupus, cancer and tuberculous laryngitis. The salient features of these various affections are most effectively presented in tabular form as follows : Chronic Catarrhal Laryngitis Syphilitic Laryngitis Cancer of Larynx History Of repeated colds Of syphilis if we can get the truth Gradually increasing hoarseness. Weakness, ema- ciation, fever. . Negative .... Early negative Negative until late in disease. Hoarseness . . . Usual but vari- able Usual after a few weeks Commonly an early symp- tom. Cougli Common, often paroxysmal. Not significant Not significant. Pain Negative .... Often none, seldom se- vere Negative early in most cases: later common Color and form. Uniform, bright con- gestion; mod- erate thicken- ing of cords and possibly walls or larynx Dull congestion and thickening, especially of epiglottis. Ulceration begins early usually at upper part of larynx. Scars often found in fauces Localized usually lateral induration and thick- ening of a dull red color. Usually involves vocal cord and parts just above it. No cicatrices. Ulceration Absent Common in tertiary. Ulcers progress rap- idly 3 or 4 mm. Deep, sharp, punched-out edges. Tendency to heal under proper treatment. Usual after five months; destruction; no tenden- cy to heal; possibilities of Aberhalden reactions. Syphilitic Laryngitis Lupus of Larynx Tuberculous Laryngitis Tests, etc Therapeutic and Wasserman tests History Negative . . . . Negative Gradual impairment of voice and slight constitu- tional disturbance. Weakness, ema- ciation, fever. Negative .... Negative for years Early, slight; become more marked in a few months. Hoarseness Usual Occasionally present; commonly absent .... May be slight or absent for a few mouths. Later, persistent and progressive. Pain Usually ab- sent Negative Negative during first few months. Persistent and severe later after ulcera- tion. Color and form. Congestion, thicken- ing ulcera- tion or scars in advanced cases Scars where healed. Thickening; one or more nodules usual on surface or edge of ulcer Early sometimes pale atrophied; usually lo- calized dull congestion and thickening. Later pale pyriform swelling of ary- epiglottic folds ; this is semi-translucent but ap- pears solid as compared with oedema. Disease usu- ally begins at lower part of larynx. Ulceration .... Common in advanced . . Always present; indo- lent nodules on sur- face or edges ; tendency to heal at one part while progressing elsewhere. Superficial grayish yel- low ulcers 1 or 2 mm. deep, irregular worm- eaten edges and surface. Very little tendency to heal unless marked consti- tutional improvement oc- curs. Tests Wasserman . . Negative . . . Tuberculin tests and pul- monary involvement. PROGNOSIS AND TREATMENT OF LARYNGEAL TUBERCULOSIS By Norval H. Pierce, M.D. university op illinois Prognosis in cases of laryngeal tuberculosis depends on various fac- tors which, bear one upon another in any given case of tuberculosis. In case of tuberculosis, infiltration of a limited area in the larynx, occur- ring in cases where the lung is not very much affected, which is running an afebrile or subfebrile course, the prognosis is favorable. In cases where the tuberculous infection first occurs after the lung has become considerably involved, where the strength is greatly diminished and where fever is continuous and high, the prognosis is invariably bad. Not only does this bear on the larynx alone, but the laryngeal conditions react unfavorably upon the pulmonary condition itself. Patients will not eat because of the pain, would rather starve. This has great influ- ence on the diminishing strength of the patient. Again, when the laryn- geal infiltration produces stenosis, the patient is deprived of sufficient oxygen thereby. It is not infrequent, however, to see in cases of the first class, where the lungs are not affected or not demonstrably affected, or where they are very slightly affected, superficial tuberculous affections of the larynx undergo spontaneous recovery. Fortunately, in this country we do not see as much tuberculous laryngitis as we see in foreign countries, especially in Vienna. I would say, too, that, as a general impression, laryngeal tuberculosis in Amer- ica, and especially among Americans, has a much better prognosis than in tuberculosis as it affects some European people. I believe that prognosis in laryngeal tuberculosis of South European individuals is much worse than the tuberculosis prognosis in a Northern German. But why this is so is pretty hard to say. It is not because of better nutrition. The same thing may be said about bone tuberculosis, or any bone inflammation for that matter. We do not see in America the devastating effect of suppurative involvement of the temporal bone, for instance, that we see in Southern Germany. Pregnancy has a very unfavorable effect on tuberculosis of the larynx, so that in certain cases the question of producing abortion may very properly be considered and the induction also of premature birth at the eighth or seventh month may also be considered in a given case. I remem- ber one woman who had a Caesarian section performed on her while in the very last stages of tuberculosis — emaciated, scarcely able to move. The child lived and the mother regained her strength and weight and was able to return to her duties at home. So that a matter of pregnancy in a case of tuberculosis of the larynx is one of great importance. Considering the treatment of tuberculosis of the larynx, it cannot 76 XORVAL H. PIEECE^ M.D. 77 be confined to local treatment. Local treatment is perhaps of secondary importance to general treatment, and the general treatment, fortunately, I am not expected to discuss in this symposium. I believe that tuberculosis of the larynx should invariably be treated in a sanatorium, wherever that is possible. It is a hospital disease. It is very pitiful to see these patients, especially with advanced tubercu- losis of the larynx, traveling in all kinds of weather from their homes to physicians' offices, and gaining little or no benefit. Perhaps it even harms them more. It is surprising to see how these same patients, when in a sanatorium, where special treatment is instituted and where con- tinuous observation can be carried out, greatly and quickly improve. I do not hesitate to say that tuberculosis of the larynx should always be treated in a hospital ; always in a special sanatorium, where it is possible. Now the treatment of tuberculosis ' of the larynx may be divided into the surgical removal of the diseased portion of the larynx and the treatment of the local suffering, we may say. The most important point in the treatment of tuberculous laryn- gitis is non-use of the voice. Absolute silence should be enforced in every case of tuberculosis of the larjTix. This has an enormous effect on the healing process of tuberculosis of the larynx. Patients should not be allowed to utter one word, at any time. All the communication with the outside world should be carried on by writing; not even the whisper voice should be allowed. So great a factor is this in the treat- ment of tuberculosis that tracheotomy has been recommended, by our German confreres especially. There is no doubt that certain cases would be vastly benefited by this procedure, but if we are to expect the best results we should select those cases that are below the age of 25, where the larynx is extremely involved, where the lung is very slightly involved, where the strength is still preserved and where the fever is not high. If we can also have a fourth item in the selection, it should be done at a season of the year or in a location where the patient can reside out-of-doors, so that the air taken into the tracheal opening shall not irritate. I have seen cases of this kind treated by tracheotomy recover. They have recovered without any other local treatment. The surgical removal of the diseased portions of the larynx should only be attempted, in my opinion, in cases where the disease is very sharply confined to given localities in the larynx, especially in the inter- arytenoid region, and you know this is the point where it most fre- quently occurs. Where it is sharply defined, then you may attempt to remove by cutting. Suspension laryngoscopy opens a new field in surgical treatment of laryngeal tuberculosis. By this method, one can operate as accurately and as safely in the larynx as one can on the surface of the skin. These growths, of course, can be operated by the indirect method. This requires, undoubtedly, very much more training. I might say that it requires more training than the younger generation of laryngologists is apt to 78 PROGNOSIS AND TREATMENT OF LARYNGEAL TUBERCULOSIS acquire, on account of the advent of direct laryngoscopy. Where the larynx is involved to any extent, where there is a voluminous infiltra- tion going on, any attempt at removal is a very great error. We know that the entire larynx has been excised for tuberculosis of the larynx. Usually it has been done through a mistaken diagnosis, tuberculosis being mistaken for carcinoma. However, there have been cases where known tuberculosis of the larynx has led to excision of the larynx and patients have invariably died within the course of three of four days from septic pneumonia, so that the removal of the larynx in tuberculosis is not considered at all any more. Neither is laryngofissure, where the larynx is cut in the middle and turned out and the tuberculous growth removed. Still, there have 'been cases reported where this operation has been followed by recovery. Now, the amelioration of local suffering. That perhaps is the most important part of the proposition in practical work. I believe that it is a great mistake to persist in local applications ex- cept in selected cases. Lactic acid does much more harm than good in cases in the infiltration stage — where there is no breaking down of the tuberculous process. I have known where patients have gone over and over again to their physician to have these tuberculous infiltrations touched up with 75 per cent, lactic acid. It does no good surely and the cough and suffering that are engendered are very harmful to the patient. The effect of lactic acid on ulcerations is, in my opinion, somewhat more beneficent. I will admit frankly that I have never seen a case of tuberculosis of the larynx cured by lactic acid alone. I have never yet seen a case cured by anything that you might put into the larynx. I have seen cases recover from tuberculosis of the larynx, but I do not know that they could have been traced to the local application of any special medicament. I have seen some cases benefitted by igni-puncture, as it is called. I have seen eases benefitted by amputation of the epiglottis when the disease is limited to this region. Sprays with creosote and menthol and what not may be of benefit in preventing or relieving irritation coughs and should always be carried out, especially in sanatoria. The use of powders in the larynx I am somewhat doubtful of; in fact any of those powders that have the reputation of being anaesthetic to the mucous membrane other than cocaine. There is a method of self -medication, where the patient puts a tube into the pharynx with a load of powder in the tube. There is a curve at the back portion of the tube which is directly over the larynx; the pa- tient inhales into the tube and insufflates his own larynx. I have seen more coughing and more distress from this method of treatment than anything else. I am, therefore, as you can readily understand, radical and very conservative regarding the treatment of the larynx. In cases G. A. TORRISON, M.D. 79 where the patient is not much affected, the lung is not much involved, fever is not high and where the strength is still present and the tuber- culosis of the larynx is localized, we should treat it surgically. The best way to control pain and cough in these patients, in my opinion, is injection in the superior laryngeal nerves with alcohol. Both nerves can be injected at the same time, if necessary. Lastly, I do not hesitate to recommend, when this painful scene is gradually drawing to an end, the abundant use of morphine. PROGNOSIS AND TREATMENT IN LARYNGEAL TUBERCULOSIS By G. a. Toreison, M.D. CHICAGO In the first place, I perfectly agree with what Dr. Kenyon has said concerning the larynx in the beginning of pulmonary tuberculosis. In almost all of the cases there is more or less congestion of the larynx. If there is general constitutional anaemia, however, we wiU. find anaemia in the larynx but in nearly every case we find some congestion of the larynx and especially in the posterior part of the larynx. I agree with Dr. Kenyon that the congestion in a great many cases is due to talking and to coughing. In many cases of pulmonary tuberculosis there is, so far as we can see, simply a laryngitis present. It is very hard, very often, to de- termine whether this laryngitis is catarrhal or tuberculous in character. As Dr. Kenyon has said, it is very important that the larynx be watched in this disease and that the laryngitis be relieved, if possible, because a simple laryngitis in the presence of pulmonary tuberculosis may pre- dispose to tuberculous laryngitis. Besides the cough, however, as the cause of laryngitis in pulmonary tuberculosis, I believe the condition of the nose plays an important part, as it does in the production of chronic catarrhal laryngitis at any time. Where there is mouth breathing and obstruction to nasal respiration, we are much more likely to find laryngeal congestion than where there is a normal nose and normal nasal breathing. As Dr. Pierce has said, the prognosis in laryngeal tuberculosis is not necessarily grave. There are a great many cases that do recover. In cases of slowly progressing pulmonary tuberculosis the laryngeal tuber- culosis may recover, while in the acutely progressing cases of pulmonary tuberculosis, in most cases when the larynx becomes involved, I think it is very rare that patients recover. 80 PROGNOSIS AND TEEATMENT OF LARYNGEAL TUBERCULOSIS The prognosis, then, of course, depends very much upon the general condition of the patient and upon the progress of the pulmonary dis- ease. If the patient has good resistance, if the pulmonary disease is only slowly progressive, laryngeal involvement does not necessarily make the prognosis absolutely bad. So far as the treatment is concerned, the most important thing, as Dr. Pierce has pointed out, is, I believe, rest. Kest of the larynx, rest of the body also, and rest of the mind. It is impossible to get rest of the larynx if you allow your patient to keep coughing, and therefore one of the most important things to control is coughing. It is also, of course, necessary to forbid the use of the voice. The patient should be forbid- den to speak ; in fact, he should be made to give his larynx as much rest as possible. The general health should be looked after. The more the patient can improve his general health, the better it will be for his laryngeal trouble. The most distressing symptom, as has been said, in laryngeal tubercu- losis is the pain. The pain interferes with nutrition and when a tuber- culous patient's nutrition is interfered with he will run down rapidly. The use of sprays is valuable, I think, in some cases and I think surgery is valuable in some cases. There has been a great deal of discussion as to the value of surgical treatment. I believe that where the laryngeal tuberculosis is localized, as Dr. Pierce has said, surgery is very often valuable, and particularly where there is ulceration. Where the general condition of the patient is fairly good and there is a slowly progressing ulceration, for instance in the interarytenoid regions, I believe that form of an ulcer can be made to heal more rapidly by the use of surgical measures than by ordinary medical treatment, by the use of sprays, for instance. I think in most cases it is good practice to punch out the granulations on the face of the ulcer and then apply lactic acid or other remedy. Lactic acid or any other, I believe, has absolutely no value except in cases of ulceration, in promoting the cure of a laryngeal tuberculosis, though there are applications which will relieve pain. Nasal Condition. I believe that in pulmonary tuberculosis and laryngeal tuberculosis, the condition of the nose is very important. It is very important to establish nasal respiration. A great many people, not only tuberculous people but others as well, have difficulty in breath- ing through the nose at night, even though not troubled during the day. In all cases of tuberculosis I think that the nose should be looked after very carefully, as well as the larynx. PREGNANCY AND TUBERCULOSIS Bt Chaeles S. Bacon, M.D. university of illinois I think Dr. Sachs is exactly right in saying that there is no general agreement as to the policy that should be pursued in dealing with this problem and I think it is true that individuals even are not clear as to what they should do in these cases. We are studying the problem still and ought to look at all sides and not approach it with any bias, one way or the other. For the proper discussion and study of the subject, it is necessary to make use of what data we have. That is not very extensive or in detail, but by making use of the figures that are given in the reports of the United States Census Bureau and comparing those with reports from other sources and making certain approximations, we may reach certain data that can be accepted for the present as more or less approxi- mately true. I am going to give figures for the United States and then reduce them to Chicago. Let me say that the population for the United States is one hundred million, which it is or will be in a year or so. The popu- lation of Chicago is approximately one-fortieth of that, or two and one-half million. Now, taking the table given in the United States Census Report of 1909, which contains the standard million, giving the population at different ages, and applying that to the present condition (we do not know whether this is exactly true or not because the standard million table of the 1910 census has not yet been made), we may say that there are about twenty-three million women in the United States of child-bearing age; that is, from fifteen to forty-five years. By the way, I should say that in some papers previously written I have given figures that differ a little from those given today, because at that time I made a computation on the basis of the years from twenty to fifty. It is better, because of the way the census reports are made, to take the other years, and also they are more accurate because there are certainly more women bearing children below the age of twenty than there are above forty-five. Taking these ages — fifteen to forty-five — and the population data of the census of 1900, we fijid that there are twenty-three million women in the United States of child-bearing age. Now the death rate in the last report, 1913, is about six per thousand for that age. That means that in the United States about 138,000 women die annually. This, of course, is approximate because we have the reports in the census only from the Registration Area, which comprises only 63.3% of the entire pop- ulation of the United States. By reducing the figures in the report to correspond with the whole United States we find that about 138,000 women die yearly, making a death rate of six per thousand, correspond- 81 82 PREGNANCY AND TUBERCULOSIS ing to a death rate of males of that period of 7.6 per thousand. Now, of these 138,000 women of the child-bearing age that die, just about 40,000 die of tuberculosis. That makes the deaths from tuberculosis 29 per cent, of all the deaths of that group, considerably over a quarter, as you see, and it makes a death rate from tuberculosis in that group of 1.7 per thousand. That corresponds to the death rate of males of 2.1 per thousand and the male tuberculosis death rate is 28 per cent, of the total death rate of that age period. That is, there are not quite the same proportion of males who die of tuberculosis as females, but there are a larger number because there are a larger number of deaths in general. Now in order to get the next element — the number of labors or the number of pregnancies — we would have to have birth statistics, and we have not these, as you know. We are practically at sea, and can take almost any multiple that we wish, but I am inclined to think that we shall not go very far astray when we say there are just about twenty- three in a thousand; the pregnancies number about twenty-three in a thousand of the whole population. That would mean that less than twenty children in a thousand are born because, as everyone knows, there are somewhere from 20 to 25 or 30 per cent of abortions, and certainly a birth rate of between eighteen and twenty in this country is not large. If I say that the pregnancy rate, then, is twenty-three per thousand of population, we shall not be very far astray. That would give us, then, about 2,300,000 pregnant women in the United States. Now, in order to get the frequency of tuberculosis, we have got to know, of course, not only the mortality from tuberculosis but also the length of life after tuberculosis occurs, and that has been variously esti- mated. I formerly took the figure five as the multiple or frequency coef- ficient, multiplying the mortality by five to get the frequency and that is also the multiple that was taken, I noticed a year or two ago, by Dr. Unterberger in Stuttgaart. I think that is rather low, especially nowadays when the diagnosis of tuberculosis is much more exact, and I think that eight is nearer the proper number. So we would say that if forty thous- sand women die annually of tuberculosis (when I say women I mean women of child-bearing age), then there will be from 200,000 to 320,000 (more nearly 320,000) tuberculous women in the United States, and if one-tenth of them are pregnant (because, as we know, there is nothing in tuberculosis that particularly prevents pregnancy), then we would say that there are every year from twenty thousand to thirty-two thou- sand tuberculous women pregnant in the United States. The other factor that we have to consider is that of mortality of children, and I say the mortality of children under five years of age, because a child is with its mother most of the time for the first five years and probably gets its infection from the mother. As you know, the mortality is not great among children under five years. About ten thou- sand children under five die annually in the United States. CHAELES S. BACON, M.D. 83 Reducing these numbers to find the Chicago data, we should have, with a population of about one-fortieth of the United States, about eight hundred tuberculous women pregnant in Chicago in a year, and that would correspond to somewhere between fifty-six to sixty thousand pregnancies in Chicago. You know, of course, in the last year or two, since the birth certificates are paid, over forty-two to forty-three thou- sand were reported in a year. I think that corresponds pretty well. With fifty-six to sixty thousand pregnancies here, there will be about eight hundred tuberculous women pregnant and about two hundred and fifty children under five years who die of tuberculosis. Now to consider the question of the effect of pregnancy on tubercu- losis. Here we come upon two entirely different views. Years ago the opinion was held by some that tuberculosis improves during pregnancy and that agrees with the experiences of a great many of us today. We know that frequently if a woman gets through the hard second and third months well, she may increase in weight and her tuberculosis seem to improve during pregnancy. It has been noted, however, by everyone, that in the puerperal period the women often run down and sometimes those who have begun badly continue to run down during their pregnancy. Now opinions, I say, differ as to the effect in general. Some, basing their conclusions on their own personal experiences in hos- pitals, find that pregnancy is always a very serious complication of tuberculosis. Why pregnancy should be a serious complication I will not discuss, except to say that the theories that chemical changes in the blood affect the tuberculous development are as yet only theories. One reason given for the increase of the tuberculous process in the early puerperium is that many of the latent tuberculous foci break down during labor. Detailed mortality statistics of tuberculous puerpera are not numerous. One of the best reports I have seen was by Dr. Catherine Van Tuessenbroeck, of Holland, who compiled the statistics of the four largest cities of Holland and made a very careful analysis, and she found this to be true, — that the mortality in the puerperal period was increased in the first six months and considerably decreased after the first six months. Dividing the first year into halves, for the first six months there was an increase in mortality, and decrease in the second six months, so that there was not a great change in the general mortality in the year. That is a rather astonishing fact but her figures seem to prove it without a doubt. At any rate, it shows that this question is not settled. It shows what we all know, — that women often do run down right after labor. But that there is very marked increase in the death rate is not quite certain. I think that the difference in the treatment of pregnant women and also of women in labor and in the puerperal period has very much to do with the death rate. If women are treated as they were twenty or thirty years ago, kept away from the air, not properly fed, they prob- 84 PREGNANCY AND TUBERCULOSIS ably will show many more signs of increase in the tuberculous process during the pregnancy. If the labor is conducted in such a way that they get some genital wound infection and later they are kept housed, kept away from the air and not fed properly, they will run down and undoubtedly pregnancy and labor would have a very serious effect. On the other hand, if the patient can be kept in ideal condition during the pregnancy, if the labor can be conducted ideally and if the woman can be kept in ideal condition afterwards, I believe that we shall find that there is not as great danger from pregnancy to the tuberculous woman as we have sometimes thought. Now another thing is to be thought of, and that is the effect on the child. We have seen that the number of deaths from tuberculosis in the first years of life is small, but still we have approximately 250 deaths in Chicago, with perhaps eight hundred tuberculous pregnant women, and it may be that most of these are from that class. This is an item not to be overlooked and in my mind is very important. Infant tuber- culosis, we are agreed, is due chiefly to infection of the child after birth, although recent observations have shown occasionally that there has been placental infection and that the child may be infected in the uterus. That does not happen very often. The chief thing is infection after birth. Now comes the question of Prevention of Pregnancy. Undoubtedly we agree that a tuberculous woman should not become pregnant. If a girl is tuberculous she should not marry, and that should be insisted upon over and over again. The question wiU arise : How long after the cure can she marry and risk a pregnancy? "We had better say two years after the cure is complete. That is, however, the shortest period. With the married women we would advise that they do not become pregnant, and this advice is to be supplemented with the best instructions that we can give. The question, however, comes up of sterilization to prevent pregnancy and that, in some cases, is to my mind justifiable, especially where the patient has no great degree of intelli- gence and where she has perhaps several living children. The only way to certainly prevent further pregnancy is by sterilization, which can be done with a tubal excision operation or with the X-ray. If the woman becomes pregnant, should abortion te induced? You have gathered from what I have already said, that I should not favor that very strongly. It certainly should not be the general rule, because of several reasons. One is this: the results of abortion are not very good. There are two indications — prophylactic and vital — for abortion to prevent further trouble, and to save the woman's life. The vital indication is worthless. If the woman is in such condition that she is pretty sure to die if she goes on with pregnancy, she will be pretty sure to die after abortion is induced, so that it is not really a reasonable indication. Possibly we want to save her to her family a CHARLES S. BACON, M.D. 85 little longer, but most authorities agree that the women go down pretty nearly as fast after the operation as without it. The prophylactic indication is the prevention of further increase of trouble in a woman that has a good hope of success in her fight with tuberculosis. Before deciding on this indication it is necessary to answer the question: How can the pregnancy be managed? Can the patient be treated in her home or sanatorium properly? If she can be sent to a sanatorium like our new Sanatorium and be cared for in an ideal way during her pregnancy, and the labor conducted in a proper way, the child taken from her and properly cared for, if that can be done I believe it is very much better than induction of abortion. It could not be done until our Sanatorium was opened, because there was no institu- tion where the patients could go. I should say that it is very seldom that induction of abortion is indicated. I think it will grow less and less as we can improve our man- agement. There is another thing I just want to say a word about — that it is a bad thing socially and morally. It is letting down the bars; it becomes an excuse for all sorts of practitioners to induce abortion, claiming that it is for tuberculosis. Now I think I have indicated in what I have said what I believe is the proper way to manage these cases. Care for them as you would for other tuberculous patients in the Sanatorium or at home if you can get the same care as at the Sanatorium. The Chicago Municipal Tuber- culosis Sanitarium has provided, as you all know, the essentials for car- rying out this treatment. The essential things are the nursery and the confinement room. The nursery where the baby is put after birth is protected from the corridor with a glass partition. The mothers do not get to the babies at all, never go into the nursery. They can see their babies through the partition and see how they are doing. Babies are to be fed with milk or possibly may use mother 's milk that is expressed or pumped from the breast. I think it will be a very interesting investigation to discover whether mother's milk is safe for the babies. If a certain amount can be given, without injury to the mother, it may be desirable to give it. The women, as soon as they are able, are taken away from the hospital and put into the cottages again, and can stay there for two or three months, and the baby stays in the nursery as long as necessary. This institution provides for twenty babies. If babies remain for three months, as they certainly ought to, provision is made for eighty patients in a year and that is my estimate as to the number of cases you will have after you get running, eighty cases in the course of a year. That can be increased, if the demand increases, as it probably will, by increasing the size of the nursery. "We have got the confine- 86 PREGNANCY AND TUBERCULOSIS ment room and other provisions. It has not been expensive and I beKeve the establishment of the maternity department is the most far-reaching improvement in the control of this important source of infection. PREGNANCY AND TUBERCULOSIS By Joseph B. DeLee, M.D. CHICAGO I believe that I am responsible, indirectly, for this meeting, or rather for the adoption of this subject for the meeting. Some months ago, while I was revising my book, I came to the chapter on "Tubercu- losis and Pregnancy," and after reading over my own production, I realized how little I knew about the subject. Happening to meet Dr. Sachs here in the corridor, I started to quiz him, believing that the larger store of information is not with the obstetrician but with the special practitioner in tuberculosis. I feel, therefore, that Dr. Sachs was very unfortunate in picking out the speakers for this meeting, at least as far as I am concerned, because I have very little information to give you. I would much prefer to get instruction from Dr. Sachs and from you all. If you will stop to think for a minute, you will see that the obstetrician seldom devotes much time to that subject, and a man in my position could not give you information on tuberculosis in pregnancy because he would look at it from the obstetrician's point of view. Cases are referred to him for operation and in many instances he receives a letter something like this : "Dear Doctor: Mrs. So-and-So has tuberculosis. I am send- ing her to you for induction of abortion. ' ' In other words, the family doctor has already made up his mind as to what is to be done and sends the case to me for operative pro- cedure. I did have, years ago however, considerable personal experience with the cases during pregnancy and afterwards. And the impressions which I got in those days are largely responsible for the opinions which I still hold. I will briefly mention some of the experiences which I had when I did have these cases during pregnancy and after labor. I do not think that these women do well during pregnancy. In those days we roughly divided them into two classes : the old chronic tuberculosis, usually in middle-aged women or rather older women; and acute tuberculosis, usually in the newly married women or women that had been married JOSEPH B. DELEE, M.D. 87 six, eight to ten years. Of course that was not arbitrary at all, but the women seemed to fall in that way. I delivered a great many tuberculous women who had hemorrhages, sweats and evening temperature, had all the signs of chronic tuberculosis, some with cavities forming, who got well and nursed the babies in spite of injunctions, and passed out of my observation, very little the worse for their experience. On the other hand, I got to look upon the young women, pregnant with the first child, who came in with a slight cough, slight evening temperature, ruddy cheeks and all appearances of health with suspicion because I found that at the end of the pregnancy they would lose their ruddy cheeks, that they stood labor poorly and went down. So I got the impression that the younger women were bad subjects and older women the better subjects. I have always had an antipathy for statistics, figures and percentages. First, my antipathy was due to laziness in collecting; and, second, it was born of distrust. I could not trust the figures, because I noticed that one man could take the figures and make beautiful deductions, and another could take the same figures and make altogether different deductions, so that the figures were not worth the labor spent to obtain them. I have gotten to look upon the opinion of the man as more valuable than statistics. I would rather take Dr. Bacon's opinion than his statistics. In sizing up, there- fore, the value of an opinion, you must take the value of the man into consideration. If he is honest with himself, has a logical mind and experience in practice, then his opinion is worth something. My opinions, therefore, regarding tuberculosis, stand on their merits, and you can put your own value on them. Within the last eight or ten years I have not followed tuberculosis cases during pregnancy or afterwards. If a woman comes to me with tuberculosis, I have always aborted her or turned to her family physi- cian, and in the eases that have been referred to me explicitly for abor- tion, I have usually performed that operation. After delivery they dis- appear. They go back to their family physicians and unfortunately I have not taken the trouble to look them up and see what became of those particular patients subsequently. Now it might interest you, in line with Dr. Bacon's remarks, if I read this article, which is rather opposed to the position I take. This abstract was taken from the Journal of the American Medical Associa- tion and I forgot to cut off the top of the page showing the name of the doctor, but he is a Hollander. — Pregnancy and Pulmonary Tuberculosis. "This article is a brief summary of the data supplied by 155 physi- cians in the Netherlands who filled out question-blanks asking for their experience with regard to the influence of a pregnancy on pulmonary tuberculosis. The detailed report is to be published in full in a Dutch gynecologic journal and it is announced that a reprint will be sent on request to Professor B. J. Kouwer, Utrecht. Among the question- blanks filled out and returned, 54 physicians reported constantly unfav- »» PREGNANCY AND TUBERCULOSIS orable experience and 27 exclusively favorable. In the 35 cases of laryngeal tuberculosis, 10 of the women survived with the pregnancy carried to normal delivery, and of the children of the 25 women with severe laryngeal tuberculosis, seven are living. ' ' Of the total 407 cases of pregnancy in tuberculous women, the dis- ease is said to have been aggravated in 184, while no harmful influence was apparent in 223 cases. In 192 cases the tuberculous women passed through more than one pregnancy ; 56 of them died of their tuberculosis. Among these, one-fifth succumbed to acute miliary tuberculosis and one-ninth in the fortnight after delivery. Many of the women passed comparatively unharmed through various complications of the preg- nancy, uncontrollable vomiting, hydramnion, pregnancy nephritis, pre- mature separation of the placenta, puerperal fever, etc., revealing remark- able resisting powers. ''On the whole, the results of the inquiry justify a stand against the prevailing pessimism in regard to the influence of pregnancy on pul- monary tuberculosis. The pregnant tuberculous woman needs, of course, good care, repose, nourishing food, etc." My early experiences were a little opposed to that, because I found that if early in pregnancy the women were tuberculous they went doMm very rapidly and I unhesitatingly recommended a therapeutic abortion. This brings me to the indications for abortion, in tuberculosis. You see, I will attack the subject from a little different angle than Dr. Bacon. He gave you the treatment of tuberculosis, and I will take up the point of indication for abortion. I have recommended abortion in cases where there has been a severe degree of anaemia. Some tuberculous women, especially those be- tween seventeen and twenty-one, and especially if they are chlorotic, if pregnancy comes on, develop a high degree of anaemia and in these women I have leaned towards the interruption of pregnancy. Then, if the woman was the mother of a large family and developed acute tuberculosis, I have not hesitated long in emptying the uterus. If the woman has hyperemesis gravidarum, there is another indication which would favor immediate emptying of the uterus. If the woman has frequent hemorrhages early in pregnancy, I con- sider that a strong indication. When a woman loses weight rapidly, has advancing cavitation and a large number of tubercle bacilli in the sputum — in other words, a rapidly advancing tuberculosis — I find it best to induce abortion. If the woman has just been married and comes very early in her pregnancy, with beginning tuberculosis, I have induced abortion, even if I thought she could carry through. I wanted her to go away and devote all her time to getting well, all her strength and power to getting well, with the understanding that two or three years (I usually say three years) after the cure has been announced by the family physician she may become pregnant, because then she can go through it safely, not once, but several times. JOSEPH B. DE LEE, M.D, 89 I have felt that the fight against tuberculosis is a serious and momentous one. It requires mental and physical stamina. It requires an intention to get well, and you all know that a great many cures of tuberculosis are interrupted by the fact that the man gives up the fight. A woman in the pregnant condition is more likely to give up the fight, so I have felt that if I could relieve her of all barriers so that she is perfectly free to fight the tuberculosis, she stands a much better show of getting well. In tuberculosis of the larynx I consider it justifiable to empty the uterus. The moral aspect of interference with pregnancy is an enormous subject and in these few minutes I would not attempt to discuss it fully. No one can disagree with Dr. Bacon that the moral aspects of abortion are too much neglected, and without question abortion is done too often. Whether or not it is morally right to kill a baby to save the mother or to prolong her life or to give her a better chance to fight disease, as I' just intimated, I am going to leave to the moralists to decide. I have gotten a great deal of solace and a great deal of strength out of an old rule which was formulated, I think, first by Confucius and later by an- other whom you are all familiar with, namely, "Do unto others as you would have them do unto you," and I feel that if I were a woman and if the question of tuberculosis and pregnancy arose, knowing as much as I do now, I would certainly want every possible barrier against my opportunity to struggle for continued existence removed. I believe that is a pretty safe course of practice. The Catholic church, as you know, absolutely forbids anything of this kind, and I know, too, that in several cases where I have recommended abortion the Catholic priest has forbidden it. The women have lived and the babies were paraded before me to make me ashamed of my recom- mendation. Of course I did not follow these cases up, and do not know what the end was, but judging from experience I can guess. Dr. Jaggard, whom you all know, said : "If you want a large num- ber of babies from that particular woman, abort her and get her per- fectly cured of the tuberculosis, and then let her bear children if cured. ' ' Another indication for abortion is kyphosis. In those cases it is better to empty the uterus because the lung capacity is already compro- mised and the tuberculosis makes rapid progress. In intestinal tuberculosis pregnancy is very rare and one should be governed by the symptoms. If the woman became pregnant, I do not believe an abortion would be strongly indicated. If you do decide to abort, what method should he used, and how are you going to do it ? I recommend that tuberculous cases be not given an anaesthetic. I have found that ether anesthesia and others, including gas, are very poorly borne by tuberculous women. They get inhalation general tuberculosis. I do not know whether anyone has had that expe- rience. The mucus is breathed up and down and infects new portions of 90 PREGNANCY AND TUBERCULOSIS the lungs and spots of tuberculosis occur all over the lungs. I have found, too, that in a few cases they have gotten a pneumonia from which they have recovered very slowly, due possibly, or probably, to the anaesthetic. This clouds the prognosis for abortion and when you are advising abortion for tuberculous women you have got to take that into consideration, — will the method of cure kill the patient? Abortion should be done in these cases without an anaesthetic if possible, in two stages, and very often one may, by injecting a one-half of one per cent, novacain solution in the fornices, operate absolutely painlessly. Now should you sterilize the woman? That depends. If you want to sterilize the woman, you have got to consider a great many factors. It is the most ugly and disagreeable operation for a man to do an abortion a second time on a woman. I will do an abortion once and empty the uterus and get her free. If she disregards injunctions and gets pregnant again, I feel I should not be asked to repeat the abortion. You might say that if the first is justifiable, why not the second? I detest the second abortion for any purpose, and I wiU never do it, nor will I do a craniotomy a second time. Nowadays craniotomy is a rare operation and if it does have to be performed the woman is warned to consult expert skill early in pregnancy so that a timely Cesarean sec- tion may be done. In sterilizing a woman, should you take off the tubes? That is the safest and quickest way of sterilization as far as life is concerned. Take off her ovaries? It has been found that a woman who has been castrated takes on fat and that is believed to prevent the increase of tuberculosis. I have seen women that were fat and very tuberculous. Should you take off the uterus to stop the menstrual flow and con- serve her strength in that way? On the other hand, the danger of hysterectomy is entirely underestimated and in individual cases you will have to balance those things very carefuUy. There are three schools as far as abortion in tuberculosis is con- cerned. The first school says, "Abort every woman that has tubercu- losis. ' ' The second school says, ' ' Abort no woman who has tuberculosis. Give her aU kinds of treatment and let her go through her pregnancy." The third school says, "Every case must be treated individually." Put me in the third school. When are you going to induce abortion? You have got to make up your mind right then. You cannot wait. Sometimes, however, if you get a case where a woman is five and one-half months pregnant, and you can tide her over six or eight weeks until the child is viable, I would consider this justifiable. When labor comes on we have to adopt a method of delivery which will reduce strain upon the lungs and heart. As soon as dilatation is complete, the forceps should be applied to obviate the bearing down effects which might provoke a hemorrhage or disseminate tuberculous pus. JOSEPH B. DE LEE, M.D. 91 In the puerperal period the patients have to be watched with exceed- ing care, although we cannot do much to prevent the complications which are going to arise. We cannot stop a miliary tuberculosis, but we might make the diagnosis and make sure that she does not have a puerperal infection, and treat her for that, when as a matter of fact she is suffering from tuberculosis. Women very often after delivery have chills, fever, etc., which are due entirely to tuberculosis and not to puerperal infection. Should a woman nurse her haby? I have allowed tuberculous women to nurse their babies and I have always found it to be without injury to either. I have insisted, however, that the baby be kept separate from the mother except when nursing. I let them nurse simply because I found that it was impossible to get my desires carried out in the matter. If a woman is well-to-do she can employ a wet nurse. But most families in which this question has arisen have not the means. So the baby has to be nursed, as in many cases the bottle-fed baby would die while the mother was busy taking care of her own health. Whether or not a tuberculous woman supplies tuberculous milk I do not know. If the milk is pumped and then fed to the baby, and there were any question about it, you might pasteurize the milk. This is under consideration, but, as I said, these questions very seldom come up to me, and I had hoped that in the general discussion I might learn more about them. CLINICAL SYMPTOMS AND PHYSICAL SIGNS IN EAELY DIAGNOSIS OF TUBERCULOSIS By F. M. Pottenger, M.D. monrovia, california I wish to thank your worthy President for the privilege and honor of addressing the members of the Eobert Koch Society today. I have chosen as my theme the clinical symptoms and physical signs in the early diagnosis of tuberculosis, and shall discuss them from the stand- point of their etiology and their relationship to one another. In studying the clinical history and symptom-complex of pulmonary tuberculosis, everyone must have been more or less impressed with the indefiniteness of the symptoms and signs connected with this disease. It is my purpose today to try to bring some order out of this chaos. There are some twenty-five or thirty different symptoms which accom- pany early tuberculosis, and even more in advanced tuberculosis; and, if we think of each symptom as an individual entity, there is no end of confusion. By carefully studying these various symptoms I have found that they all belong to three groups, according to their etiology and I offer this classification to you today. I published this first some two years ago ("Some Practical Points in the Diagnosis of Active Tubercu- losis," Northwest Medicine, January, 1914), but I can see even more clearly than I did at that time the great value of this etiological study, and I trust that this classification may be of great value to you who are working so closely in the early diagnosis of this disease. The classification which I offer is as follows: (1) Those due to toxemia; (2) those due to reflex action; and (3) those due to the tuber- culous process per se : GROUP II GROUP I Toxemia Malaise Lack of endurance Loss of strength Lack of appetite Nervous instability Digestive disturbances Loss of weight Eapid pulse Night sweats Temperature Anemia Eeflex origin Hoarseness Tickling in larynx Cough Digestive disturbances Circulatory disturbances Loss of weight Chest and shoulder pains Flushing of face Apparent anemia GROUP in Tuberculous involvement per se. Frequent and protracted colds Spitting of blood Pleurisy Sputum Temperature It is characteristic of the symptoms of tuberculosis that they are inconstant. We do not find any single symptom or any particular group of symptoms present under all circumstances. The explanation of this fact is plain when we study the symptoms according to their respective groupings. The symptoms which are best known fall in Group 1 — those due to 92 F. M. POTTENGER, M.D. 93 toxemia. It will be noticed that these are widespread in their expression, involving many different organs and parts. Aside from the anemia and rise of temperature, these all point to a disturbance on the part of the sympathetic nervous system. Further observation will show that this group of symptoms is present only under two conditions: first, during periods when the disease is definitely active and toxins are being thrown into the blood stream; and, second, when the disease is not particularly active but auto-inoculation is causing toxemia to be kept up by over- exertion, wrong habits of living, and when the sympathetic nervous system is stimulated by certain depressive emotional states such as dis- couragement and anxiety, brought on by the disease. The fact that the symptoms due to toxemia may be caused by any toxic condition, whether it be a tonsillar focus or a general intestinal toxemia or toxins from an acute infectious disease, shows that these symptoms, in themselves, cannot be relied upon in diagnosis and are only of value when considered in connection with other symptoms and signs. The further fact that distinctly active conditions in tubercu- losis are not constant until the disease reaches a state which is rather widespread shows that this group of symptoms cannot be relied upon for diagnosis. In order to have a clear conception of the symptoms which attend early tuberculosis, we must conceive of it as being a chronic inflamma- tory condition caused by irritation due to bacilli implanted in the tissues and toxins liberated by them. We must further consider that this chronic inflammation remains in a semi-quiescent condition over prolonged peri- ods of time and that, in fact, these patients often suffer from hyper- chlorhydria and spastic constipation. On the other hand, if the sym- pathetic tonus is greater these patients suffer from lack of appetite, deficiency of gastro-intestinal juices, a diminution of motility, a stasis of the intestinal contents and rapid heart action. Disturbances on the part of the heart follow the same line as just mentioned in connection with the reflex in the gastro-intestinal tract. In those patients in whom the vagus reflex predominates we may see, when the patient is at rest and free from toxemia or general sympathetic disturbances, a pulse rate normal or even below normal. Owing to the fact that the equilibrium of the pulse is disturbed by reflex action through both the sympathetic and vagus, the pulse is decidedly unstable. AYhile it may be normal or below normal, while at rest, upon exertion it may become rapid; in fact, more rapid than would occur under normal conditions, and the normal is apt to be restored more slowly than in an individual who does not have this double reflex irritation. Where the sympathetic tonus predominates, the pulse rate is higher than normal. Thus, it can be seen that a rapid pulse must not be expected under all conditions in early tuberculosis. Instability is the factor — not rapidity. In observ- ing many tuberculous patients, both in early and chronic quiescent or semi-quiescent tuberculosis, I have found a pulse rate in the sixties to 94 EAELY DIAGNOSIS OF TUBEECULOSIS be very common in that type where we would suspect a general increased vagus tonus from other symptoms. Chest and shoulder pains which appear in tuberculosis are of reflex character and due to two distinct causes. First, we have the reflex sensory manifestations which appear for the most part in the third and fourth cervical, and the fourth dorsal zones. Reflex sensory pains in tuberculosis express themselves, for the most part, in the scapular region, about the third interspace anteriorly, and in the region of the scapulae. There is also another pain of reflex origin involving certain branches of the cervical nerves. This shows itself as an aching of the shoulders ; and in some instances, in advanced tuberculosis, I have seen a deflnite inflammation of the brachial'plexus resulting from this irritation. Flushing of the face. This is a dilation of the capillaries of the head and face produced reflexly through the stimulation of the sympathetic fibres which are given off from the second and fourth thoracic segments of the cord. Apparent anemia. It might seem strange to speak of apparent anemia as being a symptom of pulmonary tuberculosis, but it has long been observed that many patients who suffer from early pulmonary tuberculosis appear pale but do not show the expected blood changes on examination. The tuberculous patient is like the patient of general enteroptotic build. He has a disturbance in the inspiratory act, due, however, to a different cause from that of the ptotic individual. The ptotic individual has a naturally deficient action of the diaphragm, and consequently a deficient inspiratory act. The tuberculous patient may have normally a full inspiratory act, or he may be of the ptotic build and have a natural deficiency; but, aside from his condition in health, when he has an inflammation in the lung, there is a motor disturbance of the muscles of inspiration, including the diaphragm, which lessens the inspiratory act. The diaphragm is the chief muscle of respiration. It receives its innervation through the phrenics, which are given off from the third and fourth, and, occasionally, from the fourth and fifth cervical seg- ments. These segments of the cord are in direct communication, reflexly, through the rami communicant es, with the sympathetics which supply the lung. Consequently we have motor disturbances in the diaphragm, as well as in the other muscles of inspiration, which result in a deficient action and limited motion of the side of the chest involved. Inasmuch as the inspiratory act is one of the chief factors in pumping the blood from the systemic veins to the right heart, we have an interference with this important function, consequently have less blood delivered to the right heart, and the heart has less blood to deliver to the arteries. The heart accustoms itself to a smaller content of blood and becomes smaller than normal, as suggested by me in a former paper (The Small Heart in Tuberculosis: A Suggested Physiological Explanation. Jour- nal of the American Medical Association, April 17, 1915). Resulting F. M. POTTENGER, M.D. 95 from these factors, we have a disturbance in the general circulatory equilibrium and a relatively smaller amount of blood in the arteries, giving us a relative arterial anemia and a relatively large amount of blood stored up in the systemic veins, particularly the splanchnics, giv- ing us venous congestion. In early tuberculosis, the congestion does not manifest itself so much because the vessels are capable of a considerable amount of compensa- tion; but, in late tuberculosis, this becomes quite evident. It will thus be seen that the symptoms of Group II, of the reflex origin, are much like the symptoms of Group I, which are due to toxemia, in that they are not distinctive of pulmonary tuberculosis. They do not point directly to the lungs. Those in Group I point to a general sympathetic discharge, involving a great number of organs supplied by this system. Those in Group II point to individual organs or parts which are bound reflexly with branches of the sympathetic and vagus nerves, and pro- duce symptoms indicative of some particular organ in which now vagus tonus and again sympathetic tonus predominates. The first group of symptoms is only present in this disease during toxemia or during depressive emotional states, which are manifested by fear, anxiety, and discouragement; while the others may be present as long as the inflammation in the lung is not thoroughly quiescent, as long as irritation of either the sympathetic or vagus nerve endings in the lung exist. Those of Group I are most prominent during attacks of acute exacerbation and are kept up by wrong methods of living and depressive emotional states. They are also widespread, involving a great portion, if not all, of the organs supplied by the sympathetic nervous system. Those symptoms of Group II, however, are extremely variable. The reflex may express itself in one organ for a time, then in another organ, and so on. But some of the sjTuptoms belonging to this group are nearly always present. That the factor which is responsible for these reflex symptoms is present over long periods of time may be inferred from the persistance of such reflex signs as we note in the muscles. In early tuberculosis the neck and chest muscles which are involved in the reflex show this increased tonus continuously; only now and then do bacilli in some particular focus take upon themselves increased activity, mul- tiply, cause necrosis, caseation of the tissues and produce the general toxic symptoms which are recognized in diagnosis. The disease process is present just the same, however, as when the acute toxic symptoms are prominent. With this understanding of the pathology we can understand how unreliable the symptoms in Group I are. Fortunately these symptoms are rarely found alone, and even when they have passed away, some of the symptoms of the other groups, together with certain physical signs, remain. The particular characteristic of the symptoms in Group II is that they aU point to organs and parts other than the lungs, but to organs 96 EARLY DIAGNOSIS OF TUBERCULOSIS and parts which are related to the lungs in their nerve supply. The lungs are innervated by the sympathetic and vagus branches of the autonomic nervous system and an irritation producing inflammation in one branch of these systems is apt to express itself in reflex action in other branches of the same system. Consequently, inflammation in the lungs sends impulses centrally, which manifest themselves in reflex action in other organs and parts connected centrally with the fibres which supply the lung. In this way all symptoms found in Group II may be explained. For example, hoarseness, tickling in the larynx and cough are reflex through the pulmonary branches of the vagus and superior and inferior laryngeal nerves. The hoarseness may be due to reflex irritation of either the superior or inferior laryngeal nerve. When due to the superior laryngeal nerve, the picture in the larynx is that of a relaxed cord. The superior laryngeal nerve furnishes sensation to the larynx and motor power to the crico-thyroid muscle, the contraction of which increases the tension of the cord. When this is irritated reflexly, we note a general relaxation and interference with normal approxima- tion, particularly of the central portions of the cords. When hoarseness is due to interference with the recurrent laryngeal, it shows itself often as an adductor paralysis, the cord of the affected side failing to approxi- mate its fellow on the other side. Tickling in the larynx is a sensory reflex through the superior laryngeal. The tickling in the larynx is the sensory impulse which precedes cough. Indigestion and loss of weight and reflex symptoms on the part of the gastro-intestinal tract are varied. They depend considerably upon the individual. There are individuals, as shown by Eppinger and Hesz (Die Vagotonic. Sammlung. Klinischer Abhandlungen. von Noorden. Heft 9 u. 10, 1910), who naturally have increased vagus tonus. There are others in whom the sympathetic tonus seems to predominate. The nature of the reflex symptoms on the part of the digestive tract in tuberculosis will depend considerably on the indi- vidual's relative vagus and sympathetic tonus. Here we have the inflam- mation in the lung sending impulses reflexly to the gastro-intestinal tract through both the vagus and the sympathetic. If the vagus tonus predominates, and it seems to do so in early tuberculosis for the most part, when the patient is not toxic, he may have even a better appetite than normal. There also may be an ample supply of gastric and intes- tinal juices and the motility of the gastro-intestinal tract may be above normal until healing occurs. We must assume that the reflex impulses which produce manifestations on the part of other organs are also con- tinuous, but that at times the equilibrium is maintained and dysfunc- tion does not appear. If we take up the symptoms in Group III it will be noticed at once that these differ from Group I and II in one important particular. With the exception of temperature, they all point to the lung. When we have sufficient inflammation in the lung to produce a tuberculous bronchi- tis, it manifests itself, as a rule, in a cough which is not unlike acute F. M. POTTENGER, M.D. 97 bronchitis and hangs on for an uncertain time. In cold weather a bronchitis that hangs on for several weeks, or any bronchitis which is repeated at intervals, should be considered as suspicious. A bron- chitis of this kind nearly always has associated with it the symptoms in Group I and some of the symptoms in Group II. This should be suf- ficient, if properly correlated, to make the diagnosis of pulmonary tuber- culosis extremely probable. These attacks of tuberculous bronchitis may not come often. They are like the exacerbations which produce toxic symptoms in this particular. They may be months apart and sometimes years. Sometimes they show only as winter coughs which continue winter after winter until a definite advanced tuberculosis manifests itself. Spitting of blood may come suddenly without any other symptoms being present. This occurs when bleeding is due to the rupture of a small vessel, caused by an old quiescent focus of small dimensions. Under such conditions, however, if there is an extension of the disease following the spitting of blood, it will probably be followed by some of the symptoms in Group II ; and others in Group I will appear. The same may be said if symptoms of activity accompany the hemorrhage. The spitting of blood should always be considered as tuberculous, unless some other cause can be definitely proven. Pleurisy has a definite meaning. In a very large percentage of cases it is tuberculous. It further is evidence of an active tuberculosis. The profession must learn that tuberculosis of the pleura is as serious as tuberculosis of any other organ, with the exception that it is usually limited in extent and, if properly regarded, offers the patient a chance for cure. Tuberculous pleurisy is a metastasis from some other focus in the body which must be active or the metastasis could not occur. Conse- quently it should he treated seriously. If the fact that there is an involvement in the pleura is not of sufficient consequence in the mind of the practitioner, that other fact — that this is an extension from some other focus which is active or the extension could not occur — should be of sufficient consequence to cause this symptom to be treated seriously. This symptom itself should make a diagnosis, unless it can be definitely proven that the pleurisy is due to some other cause. This applies to dry pleurisy, the same as to pleurisy with effusion. Symptoms of the other groups may not be present if the pleurisy is only of mild degree and limited in its extent. As a rule, however, symptoms in Group I will manifest themselves during this time and some of those in Group II. While sputum is not an early sign in tuberculosis, yet it is often present much earlier than we anticipate. Whenever the pathological process in the lung is sufficiently extensive and sufficiently virulent to cause an exudation in the tissues, there may be a slight amount of sputum present. At first this may be only mucus, but sooner or later necrosis and caseation of small tubercles occur and bacilli may be found. Sputum should always be examined regardless of the patient's opinion 98 EARLY DIAGNOSIS OF TUBERCULOSIS as to its nature. It is not sufficient for the patient to say that he has no expectoration. Give the patient suffering from early tuberculosis a bottle and require him to bring for examination all the sputum raised in twenty-four hours, forty-eight hours or even seventy-two hours. This sputum should be treated not only according to the ordinary methods of examination, but either by antiformin or by fermentation and shaking. If this careful procedure is followed, one will be surprised by often finding bacilli where unsuspected. The danger of basing a diagnosis upon the examination of a single sample of sputum in a patient with early tuberculosis can be understood if we realize that while the patient may expectorate six or eight times a day, he might not expectorate bacilli more than once in the entire twenty-four hours, or once in two or three days. The examination of a sample, unless bacilli are found, is worthless. Where bacilli are not found, the lymphocyte content should be noted. In tuberculous sputum there is often a high lymphocyte count. If 40 or 50 per cent, of lymphocytes should be found, it should be considered as suspicious. When lymphocytic or bacillary sputum is found, some of the other symptoms are nearly always present. A continued temperature was formerly thought to be tuberculous. This is not necessarily true. Any toxemia will produce temperature. Any inflammation will produce temperature, and now that we know that infectious foci may be found in other parts of the body, we must be very guarded in interpreting a slight rise of temperature as being due to tuberculosis. Temperature must have other signs and symptoms accompanying it. Temperature in tuberculosis is extremely variable. It depends a great deal on whether the patient is at rest or active. The inflammation in tuberculosis is not constant but goes in waves. There are waves of activity when the temperature will be a little higher than normal and waves of quiescence when it will be normal. No temperature curve in suspected tuberculosis is of any diagnostic value unless it extends over a period of several weeks. The temperature accompanying the menstrual period in women must be understood. For some time, anywhere from a few days to two weeks prior to the period time, the temperature is, as a rule, higher than the two weeks following the onset of the menses. It is not uncommon to find a temperature running from 98 degrees to 98.6 degrees for the two weeks following the period and running from 98.4 degrees to 99 degrees during the two weeks preceding the period. This, however, shows great variation. Premenstrual rises may only appear a day or two before the onset of the period. In some women it is even slightly lower, but the period is followed by several days' rise. We can see from the above discussion of the symptoms in tuberculosis that if they are properly analyzed, they give us diagnostic evidence; if not, they are confusing. By bearing in mind that they are produced by three different forces — toxemia, reflex action and the tuberculous process F. M. POTTENGEE, M.D. 99 itself — we can understand them better and analyze them to greater advantage than we have been able to do with our hitherto indefinite ideas of their causation. Now if we take up the question of the physical signs, we shall see how intimately they are associated with the symptoms. For example, we often see a dilatation of the pupils on the side of the involvement. This dilatation of the pupil is inconstant. Some observers have reported that they have found it in about 50 per cent of cases. It must be remem- bered that this was probably on a single examination of each patient, not a continuous observation. The pupil is innervated by both the vagus and sympathetic fibres; the vagus has a tendency to contract — the sym- pathetic to dilate ; consequently the equilibrium is disturbed. At times the patient may have a contracted pupil ; again, he may have a normal pupil, and, still again, a dilated pupil. Dilatation of the pupil is extremely common if we observe patients repeatedly during various portions of the day over long periods of time. When we find dilatation of the pupil on one side, or abnormal dilatation on both sides, we think at once of reflex disturbances from the lung. Other very important physical signs which I have described are those of motor and tropic disturbances in the muscles, subcutaneous tissue and skin over the chest. These disturbances in the skeletal muscles, sub- cutaneous tissue and skin overlying them, are due to reflex action. The inflammation in the lung sends afferent impulses through the sympathetic and the rami communicant es to the cervical segments of the cord, where they transfer their irritation to the cell bodies which give origin to filaments of the cervical nerves. This being the portion of the cord which provides motor, sensory, and trophic impulses for the superficial muscles of the chest and the skin and subcutaneous tissue overlying them, also motor and trophic impulses for the diaphragm, we find an expression of the refiex in functional and structural changes in these structures. In the case of the sterno-cleido-mastoideus and trapezius muscles we also have another reflex through the filaments of the accessorius running in the vagus. The refiexes manifested by these structures give us extremely important signs by which we may interpret the pathology within the chest. During periods of active infiammation in the lung and as long as the involvement in the lung has not healed, nerve endings are irritated, impulses travel centrally and continue their reflex irritation of nerve fibres which supply these superficial tissues. Consequently, we have, in the presence of early active inflammation in the lung, a motor reflex manifesting itself in the superflcial muscles as an increased tone (spasm). In the diaphragm it shows as altered motion. This in- creased tone in the superficial muscles may be determined sometimes on sight, but particularly on palpation. The muscles are firmer than nor- mal; the individual fibres seem to have a definitely increased tone. It is shown in the diaphragm as limited motion of the side. Another ele- 100 EARLY DLIGNOSIS OF TUBERCULOSIS ment, of course, comes in to produce this sign — decreased elasticity of the pulmonary tissue itself. That this limited motion of the side can be caused by reflex disturbance on the part of the muscles of inspiration can be proven by the fact that a very small lesion in the apex, where there is not sufficient disturbance on the part of the pulmonary elasticity to produce any appreciable effect, will produce limited motion. When the disease has persisted for a long period of time, as it does in advanced tuberculosis, we have a reflex trophic disturbance in all the parts innervated — the muscles, subcutaneous tissue and skin. The muscles also suffer a degeneration from the fact that they are kept in constant tonus for a prolonged period (overwork atrophy) . Consequently when we find a distinct degeneration of the muscles, subcutaneous tissue and the skin limited to the tissues covering one apex or both apices, we should at once think of reflex action as being the etiological factor. When an inflammation has existed in the lung for a prolonged period of time, as tuberculous infiltrations do, the skin is usually thinner than normal, the subcutaneous tissue is wasted, and when picked up between thumb and finger, shows a diminution and distinct atrophy as com- pared with that over the other apex or over other parts of the chest wall. The muscles take upon themselves certain definite changes. They lose their elasticity and appear to the palpating finger more or less doughy. The bundles also are more easily detected than in normal muscle and give the impression of being stringy. The importance of this localized atrophy, as indicating chronic inflam- mation in the lung, cannot be overestimated. If activity is also present then, aside from the atrophy, a tendency for the muscles to show increased tonus may also be detected when carefully examined ; although the general muscle tone is so low from the degeneration that this may be difficult to detect. The diaphragm reflex may be detected as a limited motion of the side, by either inspection or palpatation. We sometimes find difficulty in dis- tinguishing between the motor and trophic disturbance in the muscles, which are produced by reflex irritation and that which is produced by occupation. AVe have certain definite criteria, however, which will aid us if we find increased tone of the muscles confined to one side, partic- ularly the right side, in men who do heavy work. If this is due to occu- pation it is not so apt to involve the sterno-cleido-mastoideus as other muscles and will not involve the diaphragm. Consequently, if we find increased tonus of the muscles, which would show this change of occu- pation, and also find the diaphragm reflex — lagging on the side — and increased tonus in the sterno-cleido-mastoideus, we should suspect it to be due to reflex action produced by inflammation in the lung. It will also be noted that there is some atrophy of the muscles on the right side of most chests, due to occupational influences. Sometimes it is extremely confusing to tell whether this is wholly occupational or whether part of it is reflex as well. There are certain signs, however, which also aid in F. M. POTTENGER, M.D. 101 this dilemma. I would call attention to the fact that the sterno-cleido- mastoideus rarely degenerates from overwork. Nor does the subcutan- eous tissue. Consequently, if we find a degeneration of the stemo-cleido- mastoideus along with the other muscles and also find the subcutaneous tissue overlying the muscles atrophied, then we are justified in suspect- ing a degeneration due to pathological changes within the lung. It is important to note that these reflexes are bound up and closely associated with the reflex symptoms found in Group II. They are also accentuated at times when those symptoms in Group I are most prom- inent. Physical signs which have long been employed in the diagnosis of intrapulmonary conditions are the lagging of the chest wall and the changes on percussion and auscultation. Lagging of the chest wall, as previously mentioned, is due to both reflex motor disturbances in the muscles of inspiration and lessened elasticity in the pulmonary tissue. To be sure, it is also produced by acute pleurisy and pleural adhesions, but this, as a rule, does not have so much to do with early tuberculosis. The changes on percussion and auscultation are usually considered to be due wholly to a tuberculous process in the lung, but this is untrue. Some of our greatest errors and some of the things which have disturbed us most in diagnosis have been due to this assumption. A moment's thought will prove that we cannot neglect the influence of the superficial tissues on percussion and auscultation. When we see, as I have pre- viously described, how these are altered in the presence of activity and chronic inflammation in the lung, it can readily be seen that this influence must be taken into consideration in interpreting our signs on percussion and auscultation. The resistance to the finger or the char- acter of the sound emitted by the percussion blow is made up not only by the involvement in the lung, but the involvement in the lung, plus the soft parts, bony thorax and all other conditions present in the chest. Consequently, if, through a chronic inflammation we have a degenera- tion which amounts to a wasting of any considerable portion of the soft tissue, this must be taken into consideration in our percussion findings. It is not at all uncommon to find one-third of the soft tissue covering an apex wasted, through the reflex trophic disturbances caused by the chronic inflammation in the underlying lung. It would be necessary to have a very dense infiltration in that apex in order to make the per- cussion note equal in pitch to that on the normal side ; or make the finger resistance equal to that on the normal side. The percussion note and resistance to the finger also depend on the tone of the muscle. If, as in early tuberculosis, we have an increased tonicity of the muscle, this, of itself, gives a higher pitched note and increased resistance as compared with the normal muscle ; and a normal muscle will give higher pitch and increased resistance to the finger as compared with the degenerated muscle. I doubt not that every man who examines chests has been annoyed and perplexed very often because of his failure to recognize 102 EARLY DIAGNOSIS OF TUBERCULOSIS the effect of the soft tissue. It is impossible to compare the percussion findings in two parts of the chest or over symmetrical portions of the two lungs without first taking into consideration the relative thickness and relative tonicity of the muscles and soft tissues over the different parts. This is extremely important in early tuberculosis. One can readily understand how the auscultation findings are also influenced by the condition of the muscles. If one will listen over a degenerated muscle or a relaxed muscle, and then over the same muscle when in a state of tonicity, he will see that an impediment has been placed in the way of the conduction of sound through the muscles when in increased tone. He will also see that the sounds are higher pitched over muscles with increased tone when compared with the normal. To sum up, we can now understand that all the symptoms of tuber- culosis are an expression of: toxemia, reflex action, or of the disease process itself. The physical signs which accompany tuberculosis are also due to reflex action, and the tuberculous process itself. We can also see that the interpretation of the data obtained by the usual methods of examination, inspection, palpation, percussion and auscultation, can- not be correct unless we take into consideration not only the pathological process within the lung, but also the changes which occur in all soft tissues covering the thorax. To be more exact, we must take into con- sideration the soft structures, the bony thorax, the infiltration in the lung and all other conditions which surround it. In conclusion, I trust that this analysis of the clinical symptoms and physical signs of tuberculosis may prove as valuable to you in your work as it has been to me in mine, and I further trust that it may give you a clearer insight into this complex disease, and thus aid in the making of early diagnosis. COMPLEMENT FIXATION IN TUBERCULOSIS By H. J. CoRPEE, M.D. CHICAGO The discovery of the tubercle bacillus by Koch in 1882 placed the diagnosis of tuberculosis on a substantial foundation, but the bacillus cannot always be demonstrated early in the discharges, and frequently never appears. It also gives little clue, even if present, to the activ- ity or inactivity of the disease. Clinical findings fail to give us any direct information regarding activity or inactivity except in a crude way. Thus far biological methods of diagnosis have been of little practical value with one exception — complement fixation, which, though not fulfilling the early expectations, is gradually being improved so that there is still promise of a method being developed of equal diagnostic value to the Wassermann reaction in syphilis. The discoveries that led to the complement fixation test date back to 1874, when Traube,^ making observations on blood, concluded that blood is able to destroy bacteria. Lister, in 1881, noted that extravascular blood remains sweet despite the addition of small amounts of putrefying material. NuttalP in 1888 observed that the destruction of organisms occurred in the aqueous humour and pericardial fluid free from cells. He also noted that 56 degrees Centigrade destroyed this bactericidal activity, which became of practical applicability in destroying one of the constituents required in the complement fixation reaction. A decided advance was made when Pfeiffer observed that the cholera vibrio contains endotoxins in contradistinction to the diffusible toxins of the diphtheria bacillus and that immunity against these bacteria is produced by means other than simple neutralization of diffusible toxin. These observations led to the demonstration by Pfeiffer and Bordet of the complex nature of the bactericidal process; in short, to the demon- stration of complement in normal sera and the development of immune bodies or amboceptors in the immunized animal. Pfeiffer 's reaction may be observed in one of two ways: either (1) by rendering a guinea pig highly immune by successive inoculation of virulent cholera vibrio and then introducing into its peritoneal cavity five to ten times the ordinary fatal dose of an agar culture of cholera vibrio, or (2) injecting into a normal guinea pig a like dose of cholera vibrio with an excess of cholera immune serum from another guinea pig. In either case by removing with a pipette some of the peritoneal fluid from time to time, it is seen that the injected bacteria undergo destruc- tion and this apart from any phagocytosis. As Pfeiffer says: "They undergo solution like sugar does in water." Later Metchnikoff and Bordet showed that the same thing occurred in vitro by using definite 1. Adami. Principles of Pathology, Vol. I, 1910, p. 542. 2. ZeitBcfar. f. Hygiene, 4, 1888, p. 253. 108 104 COMPLEMENT FIXATION IN TUBERCULOSIS proportions of bacilli, inactivated (heated) immune serum, and normal serum. Loefifler and Abel (1896)^ showed that the amboceptors thus developed were far more specific than agglutinins and are unaffected by heating several hours at 60 degrees Centigrade, but are destroyed at 70 degrees Centigrade. They are not immediately produced upon inocu- lating animals with bacteria, but usually require a lapse of three to four days. Once developed they can be recognized for a considerable period of time. (demonstration OF hemolysis) To Bordet and Gengou, who in 1901 reported their results, we owe the discovery of the Bordet-Gengou phenomenon of complement fixation. To Bordet we owe the observation that if sensitized red corpuscles (i. e., corpuscles which, placed in immune serum, have taken up ambo- ceptor) be placed in normal unheated serum they take up all the com- plement, so that now this serum becomes wholly inactive for bacteriolytic or other cytolytic purposes. Similarly, if bacteria be sensitized, they absorb or fix all the complement in normal serum subsequently added. Gengou showed that a like fixation of complement takes place under conditions in which complement plays no part in the main process. Thus, if to an immune precipitin serum a trace of the antigen (protein) be added, even though the precipitate be so minute as to be invisible, the complemental bodies present in the serum become fixed and the serum subsequently cannot be employed to activate sensitized erythrocytes, etc. The same is true when toxin and antitoxin unite, a resultant fixation of complement occurs. The first practical successful application of the Bordet-Gengou phe- nomenon was developed by Wassermann and Briick in 1906, when they discovered the Wassermann reaction for syphilis. Even before this, work had been done on complement fixation for tuberculosis but with very discouraging results. The materials and methods used to date have, however, been open to severe criticism, and with slight advances and improvements the percentage efficiency of the method may be gradually increased and the future may still reveal a method of high practical applicability which may approach or even exceed the Wassermann reaction in diagnostic value. The first application of complement fixation in tuberculosis was made by Widal and LeSourd in 1901,^ who published the first results with the method as applied to tuberculosis. They obtained deviation of comple- ment in certain cases of tuberculosis, using as antigen homogeneous emul- sions of tubercle bacilli of the Arloing-Courmont strain. This was fol- lowed by a demonstration in 1903 by Bordet and Bengou^ of the presence of antibody capable of uniting with tubercle bacilli and fixing complement 3. Centralbl. f. Bakt., 19, 1896, p. 51. 4. Taken from article by Theodore Shennan and James Miller. Edinburgh Medical Jour., Vol. X, 1913, pp. 81-85. 5. J. Bordet and O. Gengou. Compt. rend. Acad, de Sci., 1903, CXXXVII., p. 351. H. J. CORPEK, M.D. • 105 in the sera of tuberculous animals. "Wassermann and Briick^ in 1906 demonstrated the presence of an antibody toward tuberculin in patients treated with tuberculin, but only examined 13 cases of pulmonary tuber- culosis. Caulfield^ (1911) examined 104 cases of pulmonary tuberculosis with bacillary emulsion as antigen and obtained 33 per cent Turban I cases, 70 per cent Turban II, and 62 per cent Turban III positive results. Laird (1912)^ examined 34 cases, making 84 tests, and obtained 24 posi- tives (in 4 cases), using watery emulsion of tubercle bacilli (which he does not describe), but his results were inconclusive. Hammer,^ using O.T. and extracted tuberculous nodules, obtained 97 per cent positive results in 46 tuberculous cases. Calmette and Massol,^*^ using prepara- tions made from tubercle bacilli by extracting with water and peptone, obtained in 134 cases 92.5 per cent fixation altogether. Fraser (1913),^^ testing a large variety of antigens, found that living tubercle bacilli gave no fixation in 96.6 per cent of normal individuals, while 42.3 per cent of tuberculous individuals gave positive reactions. Syphilitics also gave a fairly high percentage of positive results. She states that the most reliable antigen is prepared from human living bacilli, and that diagnostically the complement fixation test with living bacilli is of more value from the standpoint of positive results than any other reaction discovered to date. She believes the absence of antibodies accounts for the low percentage of results obtained. Dudgeon, Meek and "Weir^^ also tested a large number of antigens and in 102 untreated cases obtained 86 positive, while all cases treated with tuberculin gave positive results. Products of the bacilli themselves were found to be most satis- factory as antigen. With an alcoholic antigen^^ ^* prepared from tubercle bacilli they obtained of a total of 234 cases, 209 (89.3 per cent) positive, 194 of these on first examination, 11 (of the 15 negative) on second examination, and 4 more on the third examination. Besredka^^ (1913) prepared an antigen by growing tubercle bacilli (of a questionable nature since they grow in 24 to 48 hours) on egg bouillon, heating and filtering. With this antigen Bronfenbrenner^*' (1914) obtained a very high per- centage of positive results, 93.8 per cent in active cases and 55.5 per cent in convalescents, while suspected cases gave 75 per cent and syphilitic sera 24 per cent positive reactions. Inman^^ and Kuss, Leredde and Rubenstein^^ found this antigen not to be specific. Mcintosh, Fildes and Radcliffe^® (1914) also justly criticized Besredka's antigen and conclude, 6. A. Wassermann and C. Briick. Deut. Med. Wochschr., 1906, XXXII, p. 449. 7. H. Caulfield. J. Med. Research, 24, 1911, p. 122. 8. A. T. Laird. J. Med. Research, 27, N. S. 22, 1912, p. 163. 9. C. Hammer. Miinch. med. Wochschr., 1912, LIX, p. 1750. 10. Calmette and Massol. Compt. rend. Soc. de Biol., 1912, LXXIII, pp. 120 and 122. 11. Elizabeth Frazer. Zeitschr. f. Immunitats. Orig. 20, 1913, pp. 291-299. 12. Leonard S. Dudgeon, W. 0. Meek and H. B. Weir. Lancet, 1913, Vol. 184, pp. 19-21. 13. Leonard S. Dudgeon. Jour. Hygiene, 1914, Vol. 14, pp. 52-71. 14. Dudgeon, Meek and Weir. Ibid. Pp. 72-75. 15. A. Besredka. Compt. rend. Acad, de Sci., 1913, CLVI, p. 1633. 16. J. Bronfen-Brenner. Arch. Int. Med., 1914, XIV., pp. 786-803. 17. A. C. Inman. Compt. rend. Soc. de Biol., 1914, 76, p. 251. 18. Kuss, Leredde and Rubenstein. Ibid. 1914, 76, p. 244. 19. J. Mcintosh, A. Fildes and J. A. D. Radclifife. Lancet, 1914, p. 485. 106 COMPLEMENT FIXATION IN TUBERCULOSIS after testing a large number of antigens, tliat the living bacillary emul- sion is best, giving 76.7 per cent positive results in 43 definite eases of phthisis, 80.7 per cent in surgical tuberculosis, 37.5 per cent in glandular, and 87 normal individuals only gave 3 positive reactions (2 of these were in lepers and one in a case of Addison's disease). Negative results were obtained in 18 syphilitics. They look upon a positive reaction as indicative of active tuberculosis. Stimson^° (1915), who gives a fairly exhaustive table of recent literature, report;s a small number of cases using a variety of antigens but his results are inconclusive. Craig^ (1915) reports the results of examination of 166 cases of pulmonary tuberculosis, using as antigen an alcoholic extract of several strains of human tubercle bacilli which had grown on a liquid medium of alkaline bouillon containing egg, with 96.2 per cent positive results in active cases and 66.1 per cent positive in inactive cases. One hundred and fifty cases of syphilis only gave 2 positive reactions and on further examina- tion these revealed lesions in the lungs. One hundred other diseases were examined and all gave negative results. These results are certainly wonderful, but it remains for future investigators to corroborate Craig's findings and prove this antigen to be specific. As noted from a study of the literature a large number of antigens have been used, but the most reliable investigators all concede that a sus- pension of living tubercle bacilli is the only antigen of specific value and with the fewest objections. The objections to the bacillary emulsion are the small limit between the antigenic and anticomplementary dose, the turbidity produced in the tubes, and the fairly high percentage of non- specific reactions. In the hope of overcoming these difficulties, and also imitating the liberation of antigenic materials as it occurs in the animal organism, it was decided to try to obtain the antigen from the tubercle bacillus by processes as nearly identical to those that occur in the body as possible. With this in mind and realising that bacterial antigens are probably of protein character, the following investigations were carried out. In order to determine the most favorable condition for the liberation of the antigenic products from the tubercle bacillus, heavy suspensions of living tubercle bacilli of the human type were made in sterile tubes and with sterile physiological salt solution. One set of tubes was incu- bated, another set was kept at room temperature, and a third set, as control, was heated for thirty minutes in a boiling water bath to kill the bacilli and then incubated. The criterion used for determining the disintegration of the bacilli was the amount of non-coagulable nitrogen liberated by the Folin micro-method. A typical set of these results is plotted in Chart I.* There is a gradual liberation of non-eoagulable nitrogenous sub- 20. A. M. Stimson. Bull. U. S. M. H. & P. H. Serv., No. 101, pp. 7-29. 21. Charles P. Craig. Amer. Jour. Med. Sci., 1915, CL., pp. 781-790. * Note. — The complete experimental data, methods and results of this investigation will be reported in a subsequent paper. H. J. CORPEE, M.D. 107 / \, / / \ / / / ,-■ --'' /■' / \ / ^^\ ,-- '-" ~^~ ^^ [>^ ^^^ stances from the tubercle bacillus, as noted from inspection of Chart I, at incubator temperature occurring over a period reaching its maximum at about the eighth day, and this does not take place after the bacilli have been killed by heat. At room temperature this does not occur to an appreciable extent within that period of time. CHART I 0.12 0.11 0.10 0.09 0.08 0.07 0.06 0.05 0.04 0.03 0.02 0.01 0.00 MG. 12 3 4 5 6 7 8 9101112 Days N. Continuous Line Heated & Incubated Control. Dotted Line Incubated Aseptic. Dash Line Room Temp. Aseptic. CHART H 0.16 0.15 0.14 0.13 0.12 0.11 0.10 0.09 0.08 0.07 0.06 0.05 0.04 0.03 0.02 0.01 0.00 MG.O 12 3 4 5 6 7 8 9 10111213141516 Days N. Continuous Line Aseptic Autolysis in Incubator. Dotted Line is Antiseptic (Toluene") Autolysis in Incubator. The process by which these nitrogenous materials appeared was next studied. It is, of course, conceivable that it might be either a simple dissolving out of endogenous nitrogenous materials from the bacilli or it may be the result of enzyme action, an autolysis. As shown by "Wells and Corper^^ toluene will destroy the tubercle bacilli but leaves the — / \ / 1 \ / 1 ^ ^ / / / / / / / ; / / y / / / , ■ / /' / .-'-'V ^i 1 i 22. H. G. Wells and H. J. Corper. Jour. Infect. Dis., Vol. XI, 1912, pp. 288-296. 108 COMPLEMENT FIXATION IN TUBERCULOSIS enzymes intact. Chart II gives the findings when an aseptic and anti- septic (toluene) experiment are carried out at incubator temperature. From this experiment it can be concluded that autolysis of tubercle bacilli occurs, being perceptible at about the second or third day and reaching a maximum at about the sixth to eighth day at incubator temperature. The above experiments have also been repeated using bovine tubercle bacilli, and the same is found to hold true. Now that it is proven that the tubercle bacillus autolyzes, the next and most important question concerning us is whether this autolysis has any relation to the increase of antigenic strength in the autolysate. In order to test this the autolysate from a series of suspensions of tubercle bacilli in sterile physiological salt solution were tested coinci- dently at definite intervals for non-coagulable N content and titrated for antigenic strength. The latter was done by titrating varying amounts of the antigen against a four-plus tuberculosis serum and noting the amount of complement fixation obtained. CHARTm Correlation of Autolysis and Antigen Formation. Nitrogen Curve Antigen Curve D/ikYS MG. N. PER C C 0,2CC 0,ICC 0,5CC OjOlCC 0,005CC O.OOICC 0,0005CC 0,OOOICC 0.00 -I--H- + + -f- -|--f--h — — — — 1 0.00 + + + + f + + + + + — — 2 0.01 + + + ++> +,d- + + -I-4- + — — — 3 0.02 + +-I- t-+ + + +■>- 4--,+ + -h+i- -t- + + — 4 0.03 + + + + + + -I- + + + +> +-± + + + + + + 6 0.05 + + + -I-+-I- + + + + + + + +~4^ ■^-rf + + -H -h + 8 0.06 + + + ++ + + + + + -h-t- + + -1- + H- + -!- + + + + 10 0.08 + + + -t-+ + + + + + + + + + + -1-,H- + 4-+ + + 13 0.15 + +H- -t— f--f -1- -I- + -I- + + + + + + M- 4- +-I-4- + + As seen from Chart III (the dotted line joins the minimum concen- trations which give a four-plus reaction) although the nitrogen figures and the antigenic titer do not exactly increase parallel there is a certain relation between them, and it is to be noted that an antigenic titer of 0.1 c.c. on the first day becomes, gradually and consistently, a titer of 0.001 c.c. on the sixth day. Thus the autolysate from suspen- sions of living virulent tubercle bacilli becomes stronger in antigenic titer coincident with the occurrence of autolysis. In order to test the value of the autolysate antigen it was compared in a large series of cases (over 600) with the bacillary emulsion. In a general way it can be stated that the autolysate antigen possesses the following advantages over the bacillary emulsion: it has a much larger range between the antigenic and anticomplementary dose (even 0.2 c.c. of 0.001 c.c. strength has no anticomplementary effect) ; it does not lose its titer when kept on ice (several autolysates have kept their titer for four months) ; it produces no interfering turbidity in the hemolytic H. J, CORPER, M.D. 109 system; and it is more specific than the bacillary emulsion. Although more than 600 examinations were made, using the bacillary emulsion and autolytic antigens, for the sake of accurate comparison only the results from 361 cases are given in tabulated form because only such cases were included in this tabulation as were worked up accurately from the clinical standpoint. Wherever there existed any question as to the accuracy of diagnosis or where all the clinical facts did not agree perfectly the case was discarded for this purpose. The results obtained are given in Chart IV. CHAET IV Patients Exam- ined Number of Exam- inations Neg- ative E. Results Neg- ative A. Results Positive E. Results Positive A. Results Sputum V. P. Non T.B 25 26 lA 19 23 19 24 6 2* 7 2* 25- 1- 11+ Quest Non T.B.... 11 11 5 6 7 9 6 5 4 2 11- 3- 6+ Incip Inact 47 50 2A 30 39 35 43 18 9 15 7 46— 1-f Incip Act 27 30 5A 10 18 14 23 15 7 16 7 19-7+ M.A Inact 12 14 8 10 9 13 6 4 5 1 6—6+ M.A Act 47 55 8A 13 24 27 37 34 23 28 18 12-34+ F.A Inact 5 5 3 4 3 4 2 1 2 1 3-2+ F.A Active 187 216 28A 81 112 lA 110 155 107 76 105 60 15—172+ Totals 361 407 213 280 225 309 194 127 182 98 Light figures designating + and stronger positives. Heavy figures designating ++ and stronger positives. It is to be noted that the cases are divided according to the National Association classification, and that the results are given as: Neg. E. — ^negative results with bacillary emulsion; Neg. A. — negative autolysate ; Positive E. — positive bacillary emulsion, and Posi- tive A — positive autolysate. Under sputum are given the findings for tubercle bacilli in the sputum, while under V. P. are given the results of * Note. — One of these cases had received a tuberculin injection for diagnostic purposes a short time previous to drawing the blood. 110 COMPLEMENT FIXATION IN TUBERCULOSIS von Pirquet tests in the questionable and non-tuberculous cases (it is significant that all von Pirquet negatives in our series gave negative fixation tests). The complement fixation findings with the baeillary emulsion are given in two figures, the upper black figure representing the findings if a single plus is considered a positive reaction (the extreme upper figure followed by an A designates an anticomplementary result, a large predominance of these are noted under the baeillary emulsion results), while the lower red figure represents the findings if a double plus is considered positive. Using a single plus as criterion a higher percentage of positive results is obtained in the non-tuberculous and also in the more advanced cases. The double plus criterion is, how- ever, preferred since it seems to give us the more accurate view of the state of affairs (and is the same criterion used for making a plus Wasser- mann diagnosis), giving a low percentage positive in normals but also lowering the positive findings in the clinically certain tuberculosis cases. Briefly stated, the findings may be summed up as follows (considering only double-plus reactions as positive) : Only 1 non-tuberculous case out of 25 gave a positive reaction (96 per cent, negative) (the second posi- tive having received a tuberculin injection a short time previous to making the test) by both tests ; on questionable non-tuberculous cases 18 per cent, gave an autolysate test while 45.5 per cent, gave an emul- sion test; incipient inactive cases gave 14 per cent, positive reactions with the autolysate and 18 per cent, with the emulsion ; incipient active eases gave the same with both — 23.3 per cent, reactions; moderately advanced inactive cases gave 7.15 per cent, with the autolysate and 28.6 per cent, with the emulsion, while the active cases gave 37.7 per cent, with the autolysate and 41.8 per cent, with the emulsion; the far advanced inactive cases gave 20 per cent, reactions in both cases, while the active cases gave 27.6 per cent, with the autolysate and 35 per cent, with the emulsion. A greater percentage of reactions is always obtained in the active cases, but the results seem to indicate, as was pointed out by Fraser,* that antibodies in free form capable of binding antigen are apparently not always present in the sera of tuberculous individuals, but they are more liable to be present in the active form of the disease. Now we may ask : Has the complement fixation test for tuberculosis any practical value for diagnosis? Its value lies in the fact that when it is positive it practically, taken in conjunction with other findings, makes the diagnosis of tuberculosis definite. It is of value also from a differential diagnostic standpoint in pointing out tuberculosis when positive as against syphilis, abscess of the lung, empyema from other causes, carcinoma, bronchiectasis, etc. Now that the complement fixation test for tuberculosis has been found to be lacking in the point of percentage efficiency as a diagnostic test for tuberculosis, is it possible to further study the phenomenon with a view to making a more efficient test and correcting some of the possible deficiencies in the method as applied to the above investigation? The improvements suggested by the above investigation and which are at * Loc. cit. H. J. CORPER, M.D. Ill present being tried in our laboratories are the following : With a view to obtaining a higher percentage positive results a number of autolysates prepared from different strains of virulent tubercle bacilli are being tested on the same sera in order to prove whether a polyvalent autolysate antigen would be more efficient than a monovalent antigen; sera are being drawn at various intervals during the day to see whether there is a more opportune time for obtaining the antibodies in the sera, this being suggested by the periodicity of the temperature curve (weekly intervals are also being considered) ; and, finally, antigen and antibody tests are being made coincidently on the same sera, as it has been sug- gested that possibly in the absence of antibodies a test for antigen may give results.* SUMMAEY 1. Virulent cultures of tubercle bacilli free from all foreign sub- stances suspended in sterile salt solution undergo autolysis at incubator temperature as indicated by the liberation of nitrogenous substances, reaching a maximum at about the sixth to eighth day. 2. During this autolysis of virulent cultures of tubercle bacilli there is a coincident liberation of antigenic substances suitable for complement fixation for tuberculosis. This autolysate antigen possesses advantages over a suspension of living virulent tubercle bacilli as an antigen for complement fixation tests. 3. As a result of the examination of 361 patients, using both an emulsion and autolysate prepared from living virulent human tubercle bacilli as antigens, 25 normals, 11 questionable non-tuberculous and 325 definitely tuberculous cases it can be stated that : (a) The complement fixation test for tuberculosis is not an absolute test, being positive only in about 30 per cent of all the clinically definite cases of tuberculosis both active and inactive. Active cases give a higher percentage positive results than inactive cases. (b) The value of the complement fixation test for tuberculosis lies in the fact that when the test is definitely positive it practically, taken in conjunction with other findings, makes the diagnosis of tuberculosis definite. (c) It is of value also from a differential diagnostic standpoint when the diagnosis is obscure in indicating tuberculosis when positive as against syphilis, carcinoma, abscess of the lung, empyema from other causes than the tubercle bacillus, bronchiectasis, etc. 4. The practical absence of the reaction in non-tuberculous cases makes this test, when positive, of far greater value in the diagnosis of tuberculosis than any of the biological tests for tuberculosis thus far discovered. A positive test was never obtained in the absence of a von Pirquet test while a large percentage of positive von Pirquet's in normal individuals gave negative fixation tests. * Note. — In conclusion I wish to express my appreciation to Mr. H. C. Sweaney and Dr. M. Marshak for their assistance in carrying ont this work, and to Dr. J. W. Coon and the doctors of the Municipal Tuberculosis Sanitarium for their kind co-operation. TUBERCULOSIS OF THE KIDNEY By Herman L. Kretschmer, M.D. CHICAGO Tuberculosis of the kidney is one of the lesions of the higher urinary tract that has often been described as being difficult to diagnose. This traditional statement has been handed down from one author to another over a period of many years. The recent advances in genito-urinary diagnosis have proved the error of such statements. Tuberculosis of the kidney is of much more frequent occurrence than was formerly supposed, and the diagnosis can be made in each and every case. Perhaps one of the reasons why the diagnosis is not made more fre- quently is that it is not thought of as a possibility. The persistence of pus in the urine, especially in young patients, associated with fre- quency, and possibly painful urination, should always arouse our sus- picions. Very often, instead of attempting a diagnosis, these patients are treated for cystitis, pyelitis, nephritis, etc. Even when the diag- nosis of renal tuberculosis is made, the physician remarks that the patient has not lost weight, is not cachectic. In order to obtain the best possible results, a diagnosis must be made long before these symptoms supervene. Tuberculosis of the kidney is no exception to the rule that the earlier the diagnosis is made, the better the end result. That the exact opposite may be true, I have experienced in one case, in a patient who had an active tuberculosis of the kidney. Upon medi- cal management he gained thirty pounds in weight shortly after which he developed a T.B. epididymitis. Diagnosis of tuberculosis of the genito-urinary tract can very often be made without resorting to the use of special diagnostic instruments. After diagnosis has been made, special instruments must be used to localize the site of the lesion. Not infrequently one is able, as a part of the general physical examination, to obtain evidence of tuberculosis in other parts of the body, for example, lung, bone or lymph glands. Without resorting to the use of special instruments, one can obtain evi- dence of tuberculosis in the genital tract. A nodule in the epididymis or seminal vesicle, a hard, nodular infiltration of the prostate, coupled with the presence of pus in the urine, should always lead to the pre- sumptive diagnosis of tuberculosis until the cause of the pyuria and the nature of the previously mentioned nodules and infiltration are established. In women, occasionally the vaginal examination may give us infor- mation suggestive of T.B. disease of the kidney. The vaginal examina- tion may show a thick and enlarged, hard ureter. Each and every ureter that one is able to palpate through the vagina, and that may be hard and sensitive, is not necessarily of tuberculous origin. In late cases, there may often be demonstrated a variable degree of ten- 112 HERMAN L. KRETSCHMER, M.D. 113 derness over the bladder. Occasionally one is able to demonstrate the presence of a renal tumor. A great deal of care must be exercised in interpreting a renal tumor. One cannot always tell, from the amount of tenderness and the shape of the tumor, its exact nature. Indeed, the pain and enlargement not infrequently are found on the normal side, whereas the tuberculous kid- ney is not tender nor palpable. The danger, without further proof of the nature of the enlarged kidney, under such circumstances, is plain. The dangers of removing the normal kidney and leaving the tuberculous one behind are self-evident. The absolute diagnosis of tuberculous infection of the urinary tract must depend upon the demonstration of the tubercle bacillus in the urine. The older writers upon this subject recorded the rarity with which they were able to demonstrate the tubercle bacillus. More recent pub- lications, however, present a much larger percentage of positive results. In the last sixty cases, we have been able to demonstrate the tubercle bacillus in all but three cases on the stained slide. The statement has been repeatedly made that it is difficult to dem- onstrate tuberculosis in those cases associated with profuse hemorrhage. I have seen one such case in which we found bacilli. In order to dem- onstrate the presence of the T.B. in the urine, it is necessary that the urine used for examination come from both kidneys. In the rarer cases in which a stricture of the ureter exists, as a result of which no urine finds its way into the bladder, one would not be able to dem- onstrate the tubercle bacillus. The demonstration of tubercle bacilli in the urine leads to the ques- tion of determining the origin of the organisms. One should not forget that the organisms may come from the vesicles and prostate. In other words, because bacilli are found in the urine one should not come to the conclusion that they have their origin in the kidney. Although one may not be able to demonstrate the tubercle bacillus in the urine after a few examinations, if the presence of the pyuria continues, the search is usually given up. In some of these cases cul- tures, of the urine, when made, fail to reveal the presence of organisms. A persistent pyuria with negative cultures should always arouse our suspicions that we are possibly dealing with a T.B. In these cases, it might be well to resort to the guinea pig before doing a nephrectomy. The amount of pus found in the urine is quite variable. It was formerly taught that patients suffering from T.B. of the kidney always had large quantities of pus in the urine. It is but natural to expect that the amount of pus in the urine may vary within wide limits. In two of our cases, in which large clumps of pus were found at the first examination, the urine at the subsequent examination was clear, and showed but a few pus cells under the microscope, so that the fact that urine is clear and contains but a few leucocytes is no argument against 114 TUBERCULOSIS OP THE KEDNBY the presence of T.B. Not always is the urine of the tuberculous kid- ney also sterile upon ordinary culture examination. In most of our eases we found the bacillus coli. The presence of the bacillus coli may for a time mask, as it were, the tubercle bacillus. At the present time a good deal of work is being done on the treatment of colon pyelitis by lavage of the renal pelvis. One of the thoughts which should be uppermost in our minds, when carrjdng out this form of treatment, is whether or not the colon may not be associated with a tuberculosis. This, par- ticularly, in the early cases without the involvement of the bladder. The danger of coming to wrong conclusions under such circumstances is evident. In cases in which the tubercle bacilli cannot be demonstrated in microscopic slides, it becomes necessary to resort to the use of the guinea pig. It is needless to say that very often pigs are injected simply to exclude tubercle bacilli, not because one is suspected. A great deal of care must be taken in carrying out this work, as there are many possible sources of error. The value in cases in which a few organisms are present is apparent. The guinea pig has uniformly given us good results, which experience coincides with the experience of others. Ten- ney, Barney, and Young and others have recorded failures to obtain proof from the pig in positive cases. We have but one failure. In performing the guinea test, it is essential that urine from the in- fected kidney be obtained. In other words, where the ureter is obKt- erated, the guinea pig test will fail. The more accurate way would be to use two guinea pigs and to inject the right side into one pig and the left side into another. The various methods of injection need be mentioned but briefly: intrasplenic, intrahepatic and subcutaneous, either with or without previously crushing the regional lymph nodes as suggested by Block. A subcutaneous injection after crushing the lymph nodes has given us the best results, although this method has been open to criticism that should the pig have tubercle bacilli in its system they would localize here. The objections to the guinea pig test are that it requires a certain amount of time before one obtains the evidence; and, second, that the pigs may die before the tuberculous lesions have had time to develop. That one must resort to many pigs I have experienced in one case in which nine pigs were injected, solely for the purpose of exclud- ing T.B. One must be rather cautious in his interpretation of guinea pig findings. Because a pig dies of tuberculosis does not necessarily mean that the patient from whom the urine was obtained necessarily suffers from tuberculosis of the kidney. Much discussion has taken place upon this point, many authors contending that if a patient's urine contains tubercle bacilli the patient is a sufferer from renal tuberculosis. In other words, that a normal kidney does not excrete tubercle bacilli. There are others who maintain that tubercle bacilli may be excreted without the patient having tuberculosis of the kidney. It has heen HERMAN L. KEETSCHMER, M.D. 115 repeatedly stated that in order to make a positive case of T.B. of the kidney one must find the presence of pus beside the tubercle bacilli. It is also a well-known fact that kidneys have been removed, in the urine of which T.B. have been demonstrated and examination of the speci- mens after operation reveal the presence of stone or tumor. The sub- sequent examination of the urine failed to reveal the presence of bacilli. Whether or not this state of affairs exists only on one side, because of the associated pathological condition, still remains unsolved. That a patient may excrete T.B. from both sides without the presence of pus, I can vouch for, having seen one such case. Use of the tuberculin reaction as a diagnostic aid in the diagnosis of tuberculosis, I have never resorted to. Special Methods op Diagnosis After demonstrating, beyond any question of doubt, the fact that a patient has T.B., the next problem for consideration is to determine its location. This can be definitely established in the largest majority of cases by means of the cystoscopic examination and ureteral cathe- terization. There has always been more or less objection on the part of certain men to this method of diagnosis, because of so-called dangers, which it seems to me are more theoretical than real. Cystoscopic exam- inations and ureteral catheterization is of definite advantage in giving us information relative to the condition of the bladder, whether or not it is involved, and the extent of its involvement. Further information is obtained relative to the pathological side, and to the functional capacity of the kidney, which question is of serious moment when con- templating a nephrectomy. There are two conditions under which a plain cystoscopic examina- tion gives us no information and they are : First, the very early cases, before there is any involvement of the bladder, in other words in which the bladder is normal; and, second, in the very advanced eases in which cystoscopic examination cannot be carried out. These cases will be discussed in a group by themselves. • Many significant changes are those occurring around the ureteral orifice which may be in the nature of a hyperemia or oedema. Later, the edges of the ureter become rigid and gaping, finally producing a retrac- tion and ulceration. Attention has been repeatedly called to the irreg- ular distribution of areas of cystitis ; and so-called patch cystitis as being suggestive of T.B. In cases in which changes have occurred around the ureteral orifice, one may venture the diagnosis of T.B. If the oppo- site ureter is normal and under certain circumstances pathological, one may not always be in a position to give a definite expression of opinion relative to the kidney so that it is imperative to catheterize the ureters. The former teachings were that one should catheterize only the diseased side, which, of course, would leave us in the dark about the well side. The kidney which is to remain must be a well studied and worked out problem. 116 TUBERCULOSIS OF THE KIDNEY One is always desirous of knowing whether the T.B. is unilateral or bilateral. In cases where there is any doubt, we have resorted to guinea pig inoculations. Diagnostic Excision op Tissue from the Bladder Through THE CysTOSCOPE The employment of this method in diagnosis of tuberculosis of the kidney was recently suggested by Buerger, and may be of distinct value in certain obscure cases. It is not suggested that this form of diagnosis should be a substitute for the regular well recognized diag- nostic procedures, nor should it be used as a short cut to diagnosis. Nevertheless, it is quite possible to employ this method when other methods fail. This has served us in one case, where the bacilli could not be found, nor could we see a normal ureter. Around the patho- logical ureter were seen areas of edema and granulation tissue. (Lee Kind.) X-Rays The value of the employment of X-Rays in the diagnosis of this condition must naturally be limited to the advanced cases, and hence its value can never be very great, as an early diagnosis is the all-important factor in this condition. It is conceivable, however, that in some of the late cases in which cystoscopy cannot be carried out, and in which destruction of the kidney with its associated changes has occurred may be recognized on the X-Ray plate. The so-called Kittniere, of the Ger- mans, has been recognized in this manner several times. The danger of error in this method of diagnosis results from trying to diagnose too much from the plate and without taking into consideration the gross clinical evidence. Tuberculosis of the kidney, with positive plate find- ings, is frequently confused with stone. The calcified areas in T.B., however, are never so sharp and clear cut as the shadows produced by stones. The edges usually fuse into the surrounding tissue. These areas of calcification are usually found in the parenchyma. Pyelography As a routine in our diagnostic work, we have not employed pye- lography. If one uses pyelography subsequent to the diagnostic meas- ures as taken up in their order in this paper, one does not, as a rule, obtain much additional information, nor does it alter the treatment. It has been repeatedly stated that pyelography in these cases would be more dangerous than in other kidney conditions. There still remain a few cases which, for various reasons, cannot be diagnosed by one or several of the previously considered diagnostic measures. These are usually in the very advanced or late cases, patients in whom cystoscopy and ureteral catheterization are impossible. If, however, a diagnosis of T.B. of the higher urinary tract has been made. HERMAN L. KEETSCHMER^ M.D. 117 and all methods of diagnosis have been exhausted without making a diagnosis, it might become necessary to resort to some surgical opera- tion to determine whether the process is present on one or both sides. Bilateral exploratory operations have been suggested by many kid- ney surgeons. This method of exploration has been open to criticism; although the supposedly healthy kidney has been explored and its ureter and external appearance found normal, one cannot be positive that a T.B. is not present. It seems to me a much more logical method of procedure would be an extra-peritoneal dissection of the ureter on the well side, the per- formance of ureterostomy and inserting a catheter into this ureter for the purpose of obtaining urine for study from the supposedly normal kidney. Differential Diagnosis Usually not much difficulty is experienced in excluding other lesions of the urinary tract. Difficulty may arise, as previously mentioned when stone and T.B. occur in the same kidney. Gall stones but rarely have been confused. Appendicitis, on the other hand, quite frequently. A few weeks ago I saw two eases in one week; these patients had been operated on for appendicitis, although both had tuberculosis of the kidney. Occasionally, in young individuals suffering from renal tumor. a differentiation from tuberculosis may be in order. Treatment I will consider only the surgical treatment, as you are all familiar with the various diatetic, hygienic and serological methods of treat- ment of tuberculosis in general. Xor will I take up your time by going into the details of the surgical technique. Indications for Nephrectomy Not only has the mortality rate been very materially reduced and the operative results markedly improved because of the institution of early diagnosis, but also because of the institution of nephrectomy at a much earlier period in the disease than formerly. Formerly, the patients were subjected to operation only when there were either marked systemic disturbances, such as loss of weight and strength, high fever. profuse bleeding and great urinary distress. At the present time these patients are operated upon very early in the course of the disease, long before it has advanced far enough to undermine the general health of the patient. The greatest plea for an early operation is that based upon an analysis of the operative results. The early cases show a com- plete restoration of function, which diminishes in direct ratio to the duration of the disease. Chetwood sums up this subject very well when he says. '"The assem- bled facts indicate that the tendency of tuberculosis is to be progres- 118 TUBERCULOSIS OF THE KIDNEY sive, and while, as a rule, in the beginning only one kidney is involved, that there is a strong tendency later on to implicate the other organ; that the duration of life, following operation, ranges from several months to what would seem to be almost a permanent cure ; and that the operative mortality is low. ' ' These are strong arguments in favor of early operations, when tuberculosis of one kidney is established. When there are no contra-indications, nephrectomy should be carried out just as soon as the diagnosis has been definitely established. There is not much to be gained by waiting, or by instituting non-operative forms of treatment, except in those cases which will be mentioned below. Contra-Indications Before nephrectomy is undertaken, the remaining kidney must be subjected to careful study, regarding its function, in order to determine its ability to assume the added burden after the removal of the dis- eased kidney. It is also important to demonstrate the presence of a second kidney before removing the diseased one. Although absence of one kidney is rare, it is a possibility to be reckoned with. Disease in the opposite kidney is not always a contra-indication ; for example, there may be present in the opposite kidney a calculus. This can be removed by the proper operation prior to undertaking the nephrectomy. The so-called toxic albuminuria has been noted to completely disappear after the removal of the diseased kidney. While nephritis, in the opposite kidney may not be an absolute contra-indication, depending in part upon its extent and the amount of disturbed function, the prognosis is not as good under these conditions as it would be if the opposite kidney were normal. Tuberculosis of the bladder and genital organs, both for- merly considered as contra-indications, are no longer so considered. In cases with advanced pulmonary tuberculosis, nephrectomy may be resorted to as a palliative measure, in such cases associated with pro- fuse bleeding, in the cases associated with severe renal coUc, and where the patient is suffering from marked urinary distress. Not infre- quently the advisability of nephrectomy is questioned, because of the poor general condition of the patient. That is, where a patient is suffer- ing from severe anemia, loss of weight and strength. If these condi- tions are due to the kidney T.B., they cannot be considered as contra- indications. Under such conditions, it might be possible to direct treatment toward improving the general condition of the patient before performing nephrectomy. In one of our cases a gain of thirty pounds was obtained by the patient, after instituting proper management. The surgical management of bilateral tuberculosis is still unsettled. In a few instances, the more diseased of the two kidneys has been removed, in the hope of allowing the remaining kidney to heal. In view of the fact that cases of tuberculosis of the kidney do not heal under medical treatment when the disease is unilateral, it is difficult to follow HEBMAN L. KEETSCHMEK, M.D. 119 the logic of this and believe that the remaining kidney will heal. It is quite conceivable, in certain well selected cases in which the process is in its incipiency, with only a slight amount of destruction of kidney tissue, whereas the opposite kidney may be the seat of very advanced tuberculosis. Under such circumstances, it might be per- missible to remove the kidney which is the seat of advanced tuberculosis. However, if one considers nephrectomy in bilateral kidney tuberculosis from the standpoint of end result, I think nephrectomy must be con- sidered a palliative measure only. THE SPECIFIC ROENTGEN MARKINGS CHARACTER- ISTIC OF PULMONARY TUBERCULOSIS By Kennon Dunham, M.D. cincinnati It is a pleasure to come to Chicago to talk to you, but it is a much greater pleasure to bring to you my teacher, Professor Miller, who has shown me how to solve the big problem — namely : What is the anatom- ical character of the lesion which records a density upon the Roentgen plate characteristic of pulmonary tuberculosis ? He pointed out that the only way to find the answer "was to remove from the lung the part caus- ing the density and to study that part by serial sections. As it has been impossible to study the anatomy of the lungs by means of the single sections, so it is impossible to study pathological anatomy of lungs accurately except by serial sections. Before consid- ering the pathological anatomy of these lesions, let us first take up the Roentgen findings which I consider characteristic of pulmonary tuberculosis. To be able to see this density definitely, it is necessary to view the Roentgen plates stereoscopically. Then we see a triangular area of in- creased density, with the base of the triangle near the pleura and the apex pointing toward the hilus and connected with the hilus by a heavy trunk. These trunks are seen normally in the healthy chest plate passing out from the hilus and are definitely located as shown upon the screen. About midway into the parenchyma of the lung these trunks break up into finer lines which normally should radiate but do not quite reach the pleura. The early changes characteristic of tuberculosis are found in those fine radiating lines which I have termed the linear markings. Thus we have the hilus shadows and the trunks leading from them which break up into the linear markings. Great variation is seen in these triangular areas both with regard to the character and degree of the density of their markings. This is determined by the age and extent of the lesion. Thus we can usually decide definitely what part of the lung was first affected, because in that part we will have the greater density. As tuberculosis usually starts in the parenchyma beyond some one trunk much earlier than it makes its second invasion, we have a second characteristic picture of tuberculosis on the Roentgen plate, i. e., an uneven distribution of in- creased densities in contrast to the homogeneous changes which are found in other conditions, such as senility and certain forms of heart disease. In the past the Roentgen diagnosis of pulmonary tuberculosis has rested upon changes of density in the hilus and the heavy trunks. 120 KENNON DUNHAM, M.D, 121 These were read from the single plates, but such readings could not be made to correlate with the physical condition of the patient or with careful physical findings. Today I wish to show you that the earlier changes take place in the linear markings. And further, I wish to show you that these changes are due to tubercles scattered along the finer branches of the bronchial tree. These conclusions are based upon more than three thousand care- fully examined chests of which the readings of Roentgen plates and the physical examinations were carefully recorded. The work has been checked up by more than three hundred autopsies. A few of these lungs have been carefully studied by Dr. Miller and myself to ascertain exactly what pathological lesions caused the Roentgen densities. We found these early changes were due to myriads of tubercles — not one nor a few — but myriads of tubercles scattered along the bronchial tree, and that they reached completely to and into the pleura. Thus we have been able definitely to connect the Roentgen findings with a definite pathological condition. For a long time this was not easy to under- stand, because this definite distribution of the tubercles along the bron- chial tree has not been recognized by our pathologists. This paper discusses pulmonary tuberculosis involving the paren- chyma of the lung in people twelve years of age or over. "We are not speaking of miliary tuberculosis, glandular tuberculosis, peribron- chial tuberculosis or tuberculosis in children. We are speaking of the common ordinary disease known as consumption, the kind that has a first, second and third stage. It is the disease that exists in fully ninety per cent, of the adults having lung tuberculosis that come to our offices, our clinics, and are filling our hospitals. It is the disease which we are organized to fight, and about which these plates speak to us so plainly. By means of the stereo-roentgenograms of the chest we can recognize the normal chest and the tuberculous chest, and with these assured, dif- ferential diagnosis of pulmonary lesions becomes a comparatively easy matter. Syphilis gives us no increased density except in rare eases ; the distribution of carcinoma and sarcoma is usually very distinct from tuberculosis. The base and the hilus are more frequently involved and but seldom do these lesions follow the trunks. A chronic cough which is not tuberculous may show heavy trunks and hilus shadows but no change in the linear markings. Either influenza or pneumonia may show a central lesion but unless a large area is involved they do not reach the pleura and their density is usually more evenly distributed than that of tuberculosis. This differentiation should not be made from the X-ray plates alone but from the history, physical condition of the patient and physical findings, and other laboratory methods must be employed. No laboratory method will do away with the necessity of using brains. No more interesting nor accurate study can be made from these plates than the location of the initial lesions in tuberculosis. To repeat, we are not speaking of glandular tuberculosis but are speaking 122 ROENTGEN MARKINGS IN PULMONARY TUBERCULOSIS of parenchymal tuberculosis. Hippocrates, Laennec, Flint and our greatest pathologists have found initial lesions in the apices. This my X-ray findings confirm. The basal lesion dictates a grave prognosis. It is very rare to have a basal lesion without extensive and older apical lesions, except in children, and these do not reach maturity. Some- times you wiU find an early lesion in the apex of the lower lobe but this is usually associated with an older apical lesion of the upper lobe. It is probably true that the right side is more frequently involved than the left, but the left side is much more frequently the primary seat of infection than clinicians have realized. This is because tuberculosis gives physical signs more early in the upper right than in the upper left. Normal breathing has a' more bronchial sound in the upper right than in the upper left. This is because the vesicular breathing is more modified in the upper right by the sounds from the trachea. Slight lesions increase the transmission of this tracheal sound much more in the upper right than they do in the upper left. This is because the trachea lies much closer to the upper right than it does to the upper left. We have learned from the X-ray that whispering pectoriloquy in the upper left is very significant of tuberculous changes, and that the pro- longed high-pitched expiration so often found in people over fifty is also of great significance ; but the rales, except those just at the end of inspiration, frequently do not mean tuberculosis. As I have previously said in my Stereo- Clinic : To men who have never known the illumination of having their previously uncontested physical examinations constantly checked up by the bold black and white of stereo-roentgenograms, the claim I make for the necessity of their use seems based upon an inability to make good physical examina- tions or an undue enthusiasm for the Roentgen ray. But constant use of the roentgenological method since 1909, both in conjunction with my own physical examinations and those of some of the ablest men in the world, as well as with post-mortems, has enabled me to state authorita- tively that stereo-roentgenological examination of the chest has added that scientific element to the study of tuberculosis which marks another decided advance toward the understanding and the elimination of this disease. THE LYMPHATICS AND LYMPHOID TISSUE OF THE LUNG AND THEIR RELATION TO DISEASE PROCESSES By W. S. Miller, M.D. madison, wis. The anatomical unit of the lung is the lobule. Under this term two different areas have been described: 1. Those smaller areas composed of a ductulus alveolaris (terminal bronchus), the air spaces connected with it, and their blood vessels, lymphatics, and nerves. 2. Those larger areas, composed of groupings of the above defined lobules with their blood vessels, lymphatics, and nerves, which are marked out in lungs that possess a thick pleura, as in the lung of the ox and that of man, by connective tissue septa. The first of these two areas is also known as the primary lobule ; the last, composed as it is of groupings of primary lobules, form the sec- ondary lobules which in turn form the lobes of the lung. AIR SPACES It is not my purpose to enter into a detailed description of the air spaces of the lung ; the brief bibliography given at the end of this report will refer the reader to the recent literature on the subject. In Figure 1 a bronchiolus respiratorius (b.r.) is shown dividing into two ductuli alveolares (d.al.) one of which is carried out in detail. From the distal end of this ductulus alveolaris three atria (a.a.a.) arise, each of which communicates mth a variable number of sacculi alveolares (s.al.) which bear around their periphery the alveoli pulmonum (a.p.). In this particular diagram the lobule is represented as being situ- ated immediately beneath the pleura (P.), but the same relation of air spaces prevails throughout the lung. BLOOD VESSELS There are two sets of blood vessels to be considered in connection with the lung: the bronchial and the pulmonary. The former are the nutrient vessels of the lung; the latter are the functional vessels of the lung. Bronchial artery. The bronchial artery is distributed to the walls of the bronchi, the connective and the lymphoid tissue of the lung. It also supplies the lymphoglandulae of the hilum. In those lungs which possess a thick pleura and have the secondary lobules marked off by pronounced septa as in the lung of the ox, the sheep, and man, the bron- chial artery extends to the pleura and there furnishes a special blood supply to the walls of the lymphatics. In those lungs which have a 124 LYMPHATICS AND LYMPHOID TISSUE OF THE LUNG thin pleura as the lung of the eat, the dog, and the rabbit, it is the pul- monary artery which supplies the pleura with blood. Fig. 1. Schematic longitudinal section of a primary lobule of the lung (ana- tomical unit) showing the relation of the blood vessels to the air spaces and to the pleura; the position of lymphoid tissue and its relation to the air spaces, blood vessels, lymphatics, and pleura. Pulmonary artery, red; pulmonary vein, blue; lymphatics, black. Further explanation is given in the text. Bronchial veins. True bronchial veins are found only at the hilum of the lung. They empty into the vena azygos, the vena hemiazygos, or one of the venge intercostales. In all other situations the blood brought to the lung by the bronchial artery is returned by the pul- monary veins. There are no anastomoses between the bronchial artery and the pulmonary artery. The relation of the bronchial artery to the pulmonary vein will be taken up when describing the origin of the pulmonary vein. Pulmonary artery. The pulmonary artery follows in all of its sub- divisions the subdivisions of the bronchial tree. At its terminal ending it comes to occupy a central position within the lobule (Fig. 1 art. and Fig. 2) dividing into as many branches as there are atria connected with the ductulus alveolaris belonging to that particular lobule. Each W. S. MILLER, M.D. 125 atrial artery divides into branches which pass to the sacculi alveolares in the walls of which they break up into the capillary network of the lung. Pulmonary vein. The pulmonary veins arise from radicles situated in the pleura (Fig. 1; 1), from the distal end of the ductuli alveolares (Fig. 1; 2), from the place where bronchi divide (Fig. 1; 3) and from the network of capillaries into which the pulmonary artery breaks up. While the pulmonary artery, as already stated, occupies a central posi- tion in its relation to the lobule, the veins are situated on the periphery Fig. 2. Combination of three sections taken through the center of a primary lobule of the limg of a dog. DA., Ductulus alveolaris; AAA., Atria; A.S., A£., A.S., Sacculi alveolares; C, Alveolus pulmonis. The tunica muscularis of the ductulus alveolaris is indicated by the broken lines. The pulmonary artery is indicated by the vessel with a stellate opening; the pulmonary veins are in solid black. Note the two veins which arise from the ductulus alveolaris; they correspond to {2), in Fig. 1. Camera lucida drawing. of the lobule (Fig. 2). There is a single exception to this rule, namely: those veins which arise from the distal end of a ductulus alveolaris (Fig. 1; 2) are situated within the lobule (Fig. 2). The blood brought to the bronchi and the connective tissue of the lung is returned by the veins 126 LYMPHATICS AND LYMPHOID TISSUE OF THE LUNG which have their origin at the place where the bronchi divide (Fig. 1; 3) and from the distal end of the duetuli alveolares (Fig. 1; 2). LYMPHATICS . If the preceding description of the blood vessels has b- i^n thoroughly understood the description of the lymphatics will be easily compre- hended, for they follow closely the distribution of the blood vessels. Lymphatics of the hronchi. The lymphatics form within the walls of the bronchi a rich network which extends throughout the entire bronchial tree. This network communicates freely with the network of lymphatics which accompany the pulmonary artery; it also gives origin to lymphatics which leave the bronchi at the place where they divide (Fig. 1; 3) and at the distal end of the duetuli alveolares (Fig. 1:2), accompanying the veins which arise at the same place. Beyond the duetuli alveolares no lymphatics are found ; in other words, no lym- phatics are present in the walls of the air spaces. Lymphatics of the pulmonary artery. The larger branches of the pulmonary artery are accompanied by two or three main lymphatics, which are so arranged that one of them lies between the artery and the bronchus. These main trunks are connected by numerous loops and there is thus formed a network with a long mesh. The smaller divisions of the artery are, as a rule, accompanied only by a single lymphatic. The bronchial lymphatics and the arterial lymphatics are in communication with each other at the place where bronchi divide and at the distal end of the duetuli alveolares. Lymphatics of the pulmonary veins. I have just stated that the bronchial lymphatics and the arterial lymphatics communicate with each other at the distal end of the duetuli alveolares and, somewhat earlier, that lymphatics also left the bronchial network at the same place and passed to the two small veins which arise from the duetuli alveolares at this point (Fig. 2). If we follow these lymphatics we find that they join the network of lymphatics about one of the venous trunks on the periphery of the lobule (Fig. 1; 2). The lymphatics that leave the bronchi at the place where they divide follow the veins that arise at the same place and eventually join the lymphatic network about one of the main venous trunks (Fig. 1; 3). The lymphatics about the pulmonary veins also communicate with the pleural lymphatics (Fig. 1; 1). While throughout the lung the lymphatics are, as a rule, destitute of valves, a valve is present at the junction of the venous (deep) lymphatics with the pleural (superficial) lymphatics. This valve opens towards the pleura. Lymphatics of the pleura. In the pleura there is a very rich net- work of lymphatics which contain numerous valves. This network com- municates with the deep lymphatics of the lung which extend to the pleura along the pulmonary vein, but the presence of valves at the point W. S. MILLER, M.D. 127 of union permits of lymph flow, or injection masses, in only one direc- tion. It is only in occasional instances that the valves can be forced and injections made to enter the deep lymphatics from the superficial network. Previous statements that I have made on this point have been misconst] aed, possibly because the authors have been as unmind- ful of the purpose of valves as was Fabricius ab Aquapendente. Direction of lymph flow. In the lymphatics of the bronchi, of the arteries, of the main venous trunks and the greater part of the pleura, the flow is towards the hilum of the lung. In the lymphatics about the veins, the flow, in those vessels which are situated just beneath the pleura and communicate with the pleural network of lymphatics, may be towards the pleura. This probably explains why we may find tubercles in the pleura and none in the deeper part of the lung. Cunningham has recently demonstrated, from the embryological standpoint, that the lymphatics coming from the pleura covering the inferior half of the lower lobe pass through the ligamentum pulmonale and drain into preaortic lymph nodes.. I am free to confess that I have missed these lymphatics in the adult, though "Willis figured them in his illustration of the pulmonary lymphatics, published in 1675. Their course corresponds to the distribution of the bronchial artery as I have found it in the ligamentum pulmonale of the sheep. LYMPHOID TISSUE The distribution of lymphoid tissue within the lung and the relation which it bears to the air passages, the blood vessels, the lymphatics and the pleura should interest not only the pathologist, but also the clinician, for these masses frequently serve as centers to which disease processes may be conveyed through the lymph stream. Along the larger divisions of the bronchial tree, true lymph nodes have been described and figured by a number of investigators. In each instance they were found in the angle formed by the dividing bronchi. In the normal bronchioli respiratorii and ductuli alveolares I have failed to find lymph nodes or lymph follicles, but have found masses of lymph- oid tissues which were situated between the muscle coat and the accom- panying branch of the pulmonary artery. As we have seen in connection with the lymphatics, the place where bronchi divide and the distal end of the ductuli alveolares are important landmarks ; so here we find small masses of lymphoid tissue in the same situation and bearing a direct relation to the lymphatics which arise at these points (Fig. 1;2, 3). If we follow the veins and their accom- panying lymphatics, which arise at these points, to their junction with the venous trunks and the accompanying lymphatics, there will be found, in the angle formed by the union of the two veins, lymphoid tissue (Fig. 1; 2, 3). Veins which arise from the capillary network in the walls of the air spaces do not possess lymphatics or lymphoid tissue. 128 LYMPHATICS AND LYMPHOID TISSUE OF THE LUNG When lymphoid tissue is present along the course of the pulmonary artery it does not, in normal lungs, form the sheath-like arrangement described by some authors, but is found as small masses situated be- tween the artery and air spaces rather than between the artery and bronchus. In the pleura we always find a small mass of lymphoid tissue asso- ciated with the place where the radicles of the pulmonary vein unite to form a venous trunk, and the lymphatics associated with the venous trunk join the pleural network of lymphatics (Fig. 1; 1). The amount of lymphoid tissue present at this point varies with the age of the indi- vidual and the amount of pigment present; being increased in amount the older the individual and the greater the quantity of pigmentation. Lymph nodes and lymph follicles have been described as present in the pleura. I can not recognize them as normal structures. They are, in my opinion, always pathological, taking their origin from the pres- ence of irritating substances, like particles of carbon; or as an hyper- plasia of already existing lymphoid tissue, as in leucaemia. In the latter case pigmentation is usually absent. For the correct interpretation of roentgenograms, definite knowledge of the distribution of the bronchi, the arteries, the veins, the lymphoid tissue, the lymph follicles and lymph nodes within the normal lung and at the hilum is absolutely necessary; for it is impossible to correctly understand the pathological without a previous knowledge of the normal. BIBLIOGRAPHY Cunningham, R. S. MiUer, W. S. In Proc. Anatomical Record. Vol. 9, 1915. Amer. Assoc, of Anatomists. Journ. Morph. Vol. 8, 1893. Archiv. f . Anat. u. Physiol. Anatom. Abt. 1900. Amer. Journ. Anatomy. Vol. 7, 1908. Anatomical Record. Vol. 5, 1911. Journ. Morph. Vol. 24, 1913. Reference Handbook of the Medical Sciences, 3rd edition. Vol. 6, 1916. For extended literature see the 2nd edition. Note. The above report was illustrated by a series of forty-six lan- tern slides, demonstrating the various points touched upon. ^e COLUMBIA UNIVERSITY LIBRARIES This book is due on the date indicated below, or at the expiration of a definite period after the date of borrowing, as provided by the library rules or by special arrangement with the Librarian in charge. DATE BORROWED DATE DUE DATE BORROWED DATE DUE i\l\ ftWttto- m\t 6 M01 Nv lii* w ' 'f^i .^ Vi^^^^^ W** . S j\ *- \ ^■-- f- 1 Hi -IB C2a(842)M50 COLUMBIA UNIVERSITY LIBRARIES 0041070593 R0311 R54 - /| Robert Kooh society for the study J 'of tuberbulosisi Uhioago^