HEALTH SCIENCES STANDARD HX00049905 RECAP Digitized by the Internet Archive in 2010 with funding from Open Knowledge Commons http://www.archive.org/details/clinicaltubercu01pott VOLUME I CLINICAL TUBERCULOSIS CLINICAL TUBERCULOSIS BY FKANCIS MARION POTTENGER, A.M., M.D., LL.D. MEDICAL DIRECTOR, POTTENGER SANATORIUM FOR DISEASES OF THE LUNGS AND THROAT, MONROVIA, CALIFORNIA; PROFESSOR OF DISEASES OF THE CHEST, COLLEGE OF PHYSICIANS AND SURGEONS, MEDICAL DEPARTMENT, UNIVERSITY OF SOUTHERN CALIFORNIA, LOS ANGELES, CALIFORNIA. WITH A CHAPTER ON LABORATORY METHODS BY JOSEPH ELBERT POTTENGER, A.B., M.D. ASSISTANT MEDICAL DIRECTOR, AND DIRECTOR OF THE LABORATORY, POTTENGER SANATORIUM FOR DISEASES OF THE LUNGS AND THROAT, MONROVIA, CALIFORNIA. VOLUME I PATHOLOGICAL ANATOMY, PATHOLOGICAL PHYSIOL- OGY, DIAGNOSIS, AND PROGNOSIS WITH ONE HUNDRED AND FIVE TEXT ILLUSTRATIONS AND CHARTS, AND SIX PLATES IN COLORS ST. LOUIS C. V. MOSBY COMPANY 1917 Copyright, 1917, by The C. V. Mosby Company. Press of The C. V. Mosby Company St. Louis TO SIR JAMES MACKENZIE, LUDOLF KREHL, AND GEORGE W. CRILE Clinicians who Typify that Growing Spirit in Internal Medicine which Kecognizes the Importance of the Study of Pathological Physiology and Emphasizes its Application, THIS WORK IS DEDICATED By the Author. INTRODUCTION During recent years medical literature has abounded in papers and books treating of the subject, tuberculosis. Many of these contributions have been excellent. The majority of them, how- ever, have been written from a viewpoint which is entirely too narrow. If we are to make advances in our knowledge of tuber- culosis we must take a broader view than that expressed by the prevalent idea, that tuberculosis is a disease due to the tubercle bacillus, which produces a group of tubercles in the lung, and that its cure comes about as a result of good food and open air. We must look upon it as being an infectious disease producing inflammatory processes in some organ, or organs, of the body, but indirectly influencing every organ and cell of the body; and prior to the time that a specific cure has been found, we must look upon treatment as being the application of a sufficient number of remedies and measures to raise the patient's defensive powers sufficiently high to destroy the tubercle bacilli and to furnish the focal stimulation necessary to hasten scar formation. It is from this standpoint that I have approached my subject. Anatomy and physiology, both normal and pathological, have been made the basis of my studies; and visceral neurology has received unusual attention. I have endeavored to approach the study of tuberculosis from the standpoint of internal medicine in its broadest sense. I am endeavoring to present in this monograph a record of the observations which I have made during twenty years of clin- ical study. The studies, for the most part, have been made on patients in the Pottenger Sanatorium for Diseases of the Lungs and Throat, Monrovia, California. My patients have represented all stages and phases of the disease. For the most part, they have been suffering from advanced widespread lesions. They have been of an unusually intelligent class, and this has added greatly to the opportunity for careful study. In my discussion of the pathological problems I have en- deavored to make the presentation as practicable as possible. 10 INTRODUCTION My viewpoint is that of a clinician. While I have in no manner ignored the subject of cellular pathology, I have borne in mind and discussed more extensively that side of pathology which is of greater importance to the clinician, namely, functional pathol- ogy. Scientific medicine is just beginning to appreciate the im- portance of this study. In the past, functional disorders were considered as being of little concern and not worthy of legitimate study; but, as our knowledge of visceral neurology and biochem- istry increases, we, as clinicians, are learning that we should give as much, if not more attention to functional derangements than to actual organic diseases. I have discussed the nervous system more extensively than is usual in a work of this kind, and have particularly emphasized the importance of understanding the relationship of the vegeta- tive nervous system to disease. I have endeavored to indicate the important part that it plays both in being acted upon by the disease and its products, and in influencing the cellular activity in other organs and cells when so acted upon. While my discus- sion of this subject is necessarily more or less unsatisfactory be- cause of the many gaps in our knowledge, yet I have endeavored to make my treatment sufficiently complete to give those who have not had their attention directed to the importance of vis- ceral neurology a working basis for further study in this field of investigation. The study of phthisio genesis is discussed from the standpoint of tuberculous infection as a condition of childhood, from which clinical tuberculosis in the adult is a metastasis occurring after the early infection has changed the reactivity of the body cells and endowed them with the power of producing specific defensive ferments. The influence of this specific defense in warding off further infections and in changing the course of the disease by making it more chronic when implantation has occurred; like- wise its influence upon the practical problems of prophylaxis, are carefully considered. The subject of fever has received careful consideration and its relationship to the nervous system has been strongly empha- sized. Anaphylaxis has been considered in its relationship to the greater vagus division of the vegetative nervous system. The power of the body to adjust itself to new and changed con- INTRODUCTION 11 ditions has received careful attention. Such compensatory- changes as occur between the two sides of the thorax; between the thorax and abdomen; and those which take place in the cir- culatory system, have received far more attention than is or- dinarily given them. The chapters on diagnosis, as well as those on therapy, are treated in their relationship to physiology and functional pathol- ogy. The etiological classification of symptoms will be welcomed as an important advance which simplifies the picture of clinical tuberculosis and aids in its understanding. Physical examination is considered in the light of my studies of the changes in the musculature and other superficial tissues as produced reflexly by the inflammatory processes in the lungs. The importance of inspection and palpation is emphasized; and these methods of examination, probably for the first time, are given their full value in diagnosis. Percussion and auscultation are described not only in relationship' to the pathological process in the lung, but in relationship to all other changes in the organs within the thorax, as well as to the changes wrought in the muscles and subcutaneous tissues by the reflex motor and trophic impulses produced by the pulmonary inflammation. This new point of view offers an explanation of many of the errors which have always attended these methods of examination. I have endeavored to look upon the therapy of tuberculosis from a common sense viewpoint. Realizing that the most im- portant factors in the cure of tuberculosis are intelligent medi- cal guidance and faithful co-operation of the patient, these points have been everywhere emphasized throughout this work. I have endeavored to explain the physiological basis of the ac- tion of the more important measures employed in treatment, in the hope that such an understanding will produce a more intel- ligent therapy than that which is practiced today. Not only have I pointed out the benefit to be derived from each of our more important measures; but, at the same time, have shown their limitations. Psychotherapy is given an important place in therapeutics, and an attempt has been made to show the physiological basis 12 INTRODUCTION of its action in, the hope that it will find a wider application in practice. The discussion of laboratory diagnosis is not intended to be a restatement of the ordinary routine methods which are em- ployed in the examination of laboratory specimens, but a discus- sion looking towards more accurate methods and more valuable studies resulting from a critical study of laboratory specimens. This chapter is written by Doctor J. E. Pottenger, who has made the laboratory study of the patients in the Pottenger Sanatorium for the past eight years. In the tuberculosis clinic I have endeavored to give to those who are interested, but less familiar with the course of chronic tuberculosis, a definite picture of this disease through a discus- sion of individual cases which have been under the writer's care. In this I endeavor to teach the early symptomatology; to show the mistakes in diagnosis; and, by following the case during its progress, to show the relationship between symptomatology and the pathological changes which are going on within the tuber- culous process. While I realize that the temperature and pulse curves do not indicate fully the character of the pathological lesions within, yet I have used them to furnish a tangible meas- ure of the toxemia present. When necessary, I add other im- portant symptoms to make the picture clearer. I have attempted this in order to answer the many inquiries which I receive from men asking if such and such a case is not being harmed by some remedy or measure that is being used, or if some other remedy or measure will not benefit more. I wish to impress the fact that chronic tuberculosis is a disease which runs an uneven course and in which many periods of activity must be expected before a final result is attained ; and show that these periods of activity are natural, and that they do not indicate that the patient is not improving satisfactorily. The burden of my study in tuberculosis has been to find an ex- planation for the facts observed, — the reason why. I have made no effort to treat the subject in textbook style. The work should be looked upon as a series of monographs dealing with the subjects under discussion in a more or less complete manner. This has made a certain amount of repetition necessary, but, had it been omitted, it would have been to sacrifice the continuity of INTRODUCTION 13 thought. Throughout I have endeavored to make my discussions practical. I have endeavored to correlate the pathology with the symptomatology, so that the reader will think of symptoms as being an expression of functional disturbance caused by patho- logical change; and have attempted to classify the symptoms so as to aid in locating the pathological process. While much that I have written is incomplete, I trust that it will emphasize the importance of a study of this kind and stimu- late others to pursue it further. I have made no attempt to give an historical statement of the subject, nor have I attempted to review the excellent works of many observers. I have quoted freely, where the quotation added to my argument, or elucidated some point under discussion. The names of many excellent workers whose studies have added to the richness of our knowledge, and who have both consciously and unconsciously influenced my conclusions will not appear in the text, but I wish to acknowledge my indebtedness to them, the same as to those whose names are mentioned. My thanks are due to many who have aided me in preparing this book, especially to Dr. J. E. Pottenger, for preparing the chapter on laboratory methods; to Dr. R. Walter Mills, for his paper on the relationship of physical types to the form and func- tion of the internal viscera, and his excellent drawings to illus- trate the same ; to Dr. Albert Soiland, for making and reading the plates of the patients described in the chapter on x-ray diagnosis, and for furnishing the x-ray pictures for the cuts ; to Drury Victor Haight, for preparing most of the illustrations and plates; to the Misses Paine and Hardy, for preparing most of the temperature charts; to Mr. Culver, for making the charts illustrating graphi- cally the method of employing tuberculin according to the extent and degree of activity of the disease ; to Mr. Lacy, for photographs and drawings; to M. S. Pottenger, for correcting and reading the manuscript; to Miss Henrickson and Mrs. Sanford, for copying the manuscript; and, last but not least, to my assistants and pa- tients who helped me in making observations and collecting data. I desire especially to thank the publishers for their untiring ef- forts to meet the difficult problems put up to them in the mechan- ical part of the work. Francis M. Pottenger. CONTENTS VOLUME I. PATHOLOGICAL ANATOMY, PATHOLOGICAL PHYSI- OLOGY, DIAGNOSIS, AND PROGNOSIS. CHAPTER I. Pathological Changes in Tuberculosis 26 Tubercle — Collateral Inflammation — Recognition of Tuberculous In- flammations — Conglomerate Tubercle — Tuberculous Ulcer — Avenues of Infection — The Localization of Tuberculosis — Differences in Air- borne and Blood-borne Intrathoracic Diseases — The Effect of Cell Sensitization Upon the Implantation ,of Bacilli — Lymphatic Metas- tasis — Bronchogenous Metastasis — Hematogenous Metastasis — Forms of Tuberculosis — Miliary Tuberculosis — Fibroid Tuberculosis — Case- ous Tuberculosis — Fibrocaseous Tuberculosis — Non- tuberculous Changes in Other Organs — Degeneration — Amyloid Degeneration — Fatty Degeneration — Cloudy Swelling — General Congestion — Changes in Nerves — Changes in Muscles — Changes in the Skin and Subcu- taneous Tissue — Changes in Blood Vessels — Non-pulmonary Tuber- culosis — Nasal, Tonsillar, and Pharyngeal Tuberculosis — Laryngeal Tuberculosis — Tuberculous Pleurisy — Tuberculous Pericarditis — Tu- berculous Peritonitis — Tuberculous Enteritis — Tuberculosis of the Liver — Tuberculosis of the Spleen — Tuberculosis of the Glands. CHAPTER II. The Source and Routes of Infection and the Primary Focus ... 57 Source of Infection — -Bovine Infection Cannot be Differentiated from Human Infection Either by Localization or Character of the Lesion — Incubation Period in Tuberculosis — Infection Through the Respiratory Tract — Comparison of Infection in Tuberculosis and Def- inite Air-borne Disease — Droplet Infection — Infection Through the Alimentary Tract — Tonsils — Infection Through the Digestive Tract — Difficulty of Determining Source of Infection — Other Methods of Infection. CHAPTER III. Relationship of the Primary Focus to Clinical Tuberculosis ... 82 Differentiation Between Primary Focus and Primary Metastasis — Tu- berculosis Primarily a Lymphatic Disease — Metastatic Tuberculosis — ■ Relationship of Primary Metastasis to Clinical Tuberculosis — Infec- tions from Without in Later Life. 16 CONTENTS CHAPTER IV. Tuberculosis in Childhood 93 The Natural Defense of the Little Child — 'Infection and Immunity — The Difference in the Tuberculous Process at Different Age Periods — What Predisposes a Child to Infection — Frequency of Tuberculosis in Children — Fate of Early Lesions — The Effect of Tuberculous Infec- tion Upon the Child — The Importance of Eecognizing Latent or Par- tially Latent Lesions in Early Life — Tuberculosis of the Mesenteric Glands — The Diagnosis of Active Glandular Tuberculosis. CHAPTER V. Factors Which Predispose to Tuberculosis. Why the Apex is In- volved. A Critical Study of Freund's Theory of the Ossi- fication of the First Costo-Sternal Articulation and Short- ening of the First Costal Ring, as Predisposing Factors in Apical Tuberculosis 117 Disposition and Predisposition — Pulmonary Focus — Metastatic Tuber- culosis — Commonly Recognized Factors Predisposing to Formation of Pulmonary Metastases — Localization in the Child and Adult Differs — Anatomical Facts Bearing on Pulmonary Infection — Apical Compres- sion Following Anatomical Growth Slows Blood and Lymph Cur- Tent — Critical Examination of Theories of Freund, Schmorl and Rothschild — Habitus Phthisicus — The Small Heart. CHAPTER VI. The Nervous System in Tuberculosis 150 Psychoses — Psycho-Neuroses — Pathology of Psychoses and Psycho- neuroses — Tuberculosis and the Peripheral Nerves — Pathology of Neu- ritis in the Tuberculous. CHAPTER VII. The Nervous System (Continued) : The Vegetative Nervous System in its Relationship to Diseases of the Lungs : A Discussion of Principles, Including the Antagonistic Action Which is Manifested Between the Greater Vagus and Sympathetic Divisions . . . , 168 Joint Chemico-Physical, Sensori-Motor and Psychical Control — The Vegetative Nervous System — The Inhibitory Action of Visceral Nerves — Grouping of Structures Supplied by the Sympathetic and Greater Vagus Systems — Symptoms Due to Stimulation of Vegeta- tive Nerves are Variable — Segmentation of the Body — Segmental Relationship of the Lungs — Lungs Embryologieally Formed From In- testine — The Relation of Symptoms in Tuberculosis to the Greater Vagus and Sympathetic Divisions of the Vegetative Nervous System — Antagonistic Action of Greater Vagus and Sympathetic Fibers Shown in Variability of Symptoms — Effect of Internal Secretions on Symp- tomatology — Internal Secretion of the Thyroid — Internal Secretion of the Ovary — Antagonistic Action of Greater Vagus and Sympathetic as Shown in Symptoms of Pulmonary Tuberculosis — Dilated Pupil — Hectic Flush — Heart — Intestinal Tract — Influence on the Salivary Flow — Tongue Atrophy — Motor and Sensory Disturbances in Pharyn- geal Structures — Coated Tongue — Stomach — Intestines. CONTENTS 17 CHAPTER VIII. The Nervous System (Continued) : The Relationship of the Sympa- thetic Nervous System to Toxemia and the Depressive Emo- tional States in General 217 CHAPTER IX. The Circulatory System in Tuberculosis 230 Nervous Influences Upon the Heart in Tuberculosis — Physiological Facts — Effect of Pathological Reduction in Pulmonary Areas — Blood Pressure in Tuberculosis — Small Heart and Arteries — Hypertrophy of Right Ventricle — Thickening of Arteries in Tuberculosis — Tubercu- lous Lesions of the Blood Vessels — Difficulties in Examining Heart in Tuberculosis — Organic Heart Lesions and Tuberculosis — Heart Bruits — Degeneration of Heart Muscle — Clinical Evidence of Failing Heart — Treatment of Failing Heart. CHAPTER X. The Digestive System in Tuberculosis 251 General Observations on Nutrition — Nutrition in Tuberculosis — The Digestive Tract and the Vagus and Sympathetic Nervous Systems in Tuberculosis — Appetite — Disturbance on the Part of the Stomach — Hypochlorhydria — Hyperchlorhydria — Dilatation of the Stomach — Disturbance on the Part of the Intestines — Enterocolitis — Diet Per- mitted in Severe Cases — Moderately Severe Cases — Mild Cases — Foods Forbidden — Intestinal Stasis — Constipation — Atonic Constipation — Spastic Constipation — Biliousness (So-called) — Nervous Influences in Gastro-Intestinal Disturbances- — Amyloid Degeneration — Errors in Diet. CHAPTER XI. Compensatory Changes in the Thoracic and Abdominal Cavities Re- sulting From Pulmonary Tuberculosis 281 Compensatory Changes Taking Place Within the Thoracic Cavity — Shifting of Mediastinum — Displacement of the Heart — Effect of Dis- placement of the Heart — Compensatory Changes in Thoracic Cage — Compensatory Changes Taking Place Between the Thoracic and Ab- dominal Cavities in Pulmonary Tuberculosis — The Inspiratory Act — Inspiratory Act and Circulation — Symptoms Following Deficient In- spiratory Act — Particular Alterations in Position and Function of the Diaphragm in Pulmonary Tuberculosis — Effect of Arterial Hypoten- sion and General Wasting of Tissues upon Body Activities. CHAPTER XII. Traumatic Tuberculosis 312 CHAPTER XIII. Important Anatomical and Physiological Facts to be Considered in Making Physical Examination op the Organs Within the Thorax 319 Projection of Lung on Anterior Surface of Chest — Normal Border of Lungs — Position of Diaphragm at Different Age Periods — Position of 18 CONTENTS Sulci Which Separate Lobes — Projection of Peritracheal and Peri- Bronchial Glands on Body Surface — Muscles Employed in Normal Eespiration — Influence of Diaphragm in Eespiration — Muscles Em- ployed in Forced Eespiration — Segmental Distribution of Nerves to the Somatic Muscles — Importance of Muscles and Soft Tissues on Physical Findings — Normal Well-Formed Thorax — Common Occupa- tional Changes in the Soft Tissues of the Thorax — The Eelation of Visceral Form — Topography and Function to the General Physique, with a Classification of Types. CHAPTEE XIV. The Diagnosis of Early Pulmonary Tuberculosis: History and Clinical Symptoms 357 Clinical Tuberculosis — Eelationship of Clinical Diagnosis to Infec- tion — Clinical Diagnosis — Family History — Clinical History — History of Past Illness — Slow Eeeovery from Other Diseases — Present Ill- ness — Classification or Early Symptoms — General Characteristics of Toxic Group — Symptoms Due to Tubercle Toxins — Malaise, Nervous Instability, a Feeling of Being Eun Down, Lack of Endurance — Gastro-Intestinal Symptoms — Night Sweats — Eise in Temperature — Acceleration of the Pulse — Symptoms of Eeflex Origin — Hoarseness — Tickling in the Larynx and Dry Hacking Cough — Disturbance in Heart Action — Loss of Weight — Chest and Shoulder Pains — Flushing of the Face — Symptoms Due to the Tuberculous Process Itself — Fre- quent and Protracted Colds — 'Spitting of Blood — Pleurisy — Sputum — Temperature — Eelative Value of the Various Groups of Symptoms. CHAPTEE XV. The Diagnosis of Early Pulmonary Tuberculosis: Physical Exam- ination of the Patient 394 General Considerations — Favorable Conditions for Making Examina- tion Important — Methodical Examination Necessary — Physician's Duty in Suspected Cases — Etiological Classification of the Changes Found on Physical Examination — Factors Causing Changes on In- spection, Palpation, Percussion and Auscultation — Factors Which Af- fect Soft Structures Covering the Bony Thorax — Cause of Eeflex Spasm and Degeneration of Soft Tissues — Example of the Effect of Spasm and Degeneration — Inspection — Dilatation of the Pupil — Lag- ging, Eegional and General— State of Muscles and Subcutaneous Tis- sue—Occupational and Pathological Changes in Soft Parts Covering the Apex— Change in Contour of Trapezius Muscle— Mammary Gland — Palpation — What Can be Determined by Palpation — Eegional Spasm of Muscles — Eegional Atrophy of Skin, Muscles and Sub- cutaneous Tissue — Determining of Pulmonary Infiltrations by Pal- pation — Lagging — Tactile Fremitus — Enlarged Glands — Percussion — Light or Heavy Percussion — Percussion Changes in Early Clinical Tuberculosis — Conditions Within the Chest Which Alter the Per- cussion Note — Percussion Gives No Evidence of Activity — Kroenig's Apical Percussion — Auscultation — Stethoscope — Method of Breathing During Auscultation— The Effect of Muscles on the Eespiratory Note — Eespiratory Sounds in Early Tuberculosis — Weakened and Im- peded Breathing— Why Eespiratory Sounds Differ in Early Tuber- culosis—Interpretation of Auscultatory Findings— Whispered Voice. CONTENTS 19 CHAPTER XVI. The Signs and Symptoms of Advanced Pulmonary Tuberculosis . . 435 General Considerations — Classification of Symptoms of Advanced Tuberculosis — Malaise, Lack of Endurance, and Loss of Strength — Digestive Disturbances — Loss of Weight — Circulatory Disturbances — Night Sweats — Fever — Hoarseness — Tickling in Larynx and Cough — Chest Pains — Symptoms on the Part of the Nervous System — Acid- osis — Dyspnoea — 'Hectic Flush — Sputum — Pleurisy — Frequent and Pro- tracted Colds — Hemoptysis — Menstruation. CHAPTER XVII. The Physical Examination of the Patient in Advanced Pulmonary Tuberculosis 464 Inspection — Muscle Spasm; and, Degeneration of Muscles, Subcuta- neous Tissue and Skin — Changes in Contour and Movement of Chest Wall — Palpation — Palpation of Muscles and Subcutaneous Tissue — Motility of Chest Wall — Determination of Different Degrees of Den- sity by Palpation- — Percussion — Auscultation — Respiratory Rhythm — Quality of Note — Rales — Adventitious Sounds Resembling Intrapul- monary Rales — Extensive Infiltration in One Lung — Fibrosis — Cav- ity — Compensatory Emphysema — Dry Pleurisy — Pleural Effusion — Thickened Pleura — Mediastinal Thickening. CHAPTER XVIII. Tuberculin Tests in Diagnosis 502 General Considerations — The Subcutaneous Test — Temperature — The Cutaneous Test (von Pirquet) — The Percutaneous Test (Moro) — The Conjunctival Test (Wolff-Eisner) — The Intradermal Test. CHAPTER XIX. The X-Ray as an Aid to the Diagnosis of Pulmonary Tuberculosis . 516 Relative Value of Physical and X-Ray Examinations — Interpreta- tion of Plate — The Normal Hilus and Trunk Shadows — Method of Using X-Ray in Pulmonary Diagnosis — Cases Illustrating Compara- tive Results of Clinical and Stereoscopic Examination. CHAPTER XX. Laboratory Methods 533 Sputum — 'Collection of Specimens — Cytological Examination — Fermen- tation and Determination of Sediment Volume — Albumen Reaction — Studies on the Distribution of Tubercle Bacilli in Sputum and Other Conditions of Importance in Their Demonstration — Technics for the Preparation of Sputum— Staining of Tubercle Bacilli— Number of Tubercle Bacilli — Morphological Classification — Urine — Collection of Specimens — Diazo Reaction — Urochromogen — Indiean Determination — Blood — General Differentiation — Arneth's Classification of Neutro- phils — Neuclear and Protoplasmic Changes in the Neutrophile — Feces — Interpretation of Laboratory Findings. 20 CONTENTS CHAPTEE XXI. The Diagnosis and Differential Diagnosis of Tuberculosis, Particu- larly Pulmonary Tuberculosis 596 The Importance of Diagnosis in Hidden Tuberculosis — Difficulties of Diagnosis — The Importance of the Tuberculin Tests in Diagnosis — Variability of Tuberculins — Importance of Clinical History in Diag- nosis — What Value Has Physical Examination in Diagnosis — The X- Eay in the Early Diagnosis of Tuberculosis — Differential Diagnosis — General Asthenic Constitution — Neurasthenia — Malaria — Acute or Subacute Bronchitis — Intercostal Neuralgia — Influenza — Chronic Pur- ulent Bronchitis and Bronchiectasis — Chronic Fibrosis — Pulmonary Infarct — Pneumonia — Pulmonary Syphilis — Actinomycosis — Strepto- thricosis — Blastomycosis, Aspergillosis, and Coccidioidal Granuloma — Malignant Tumors of the Lung. CHAPTEE XXII. Prognosis 624 Introductory Eemarks — Age — Constitution — Environment — Economic Status — Mental State — ^^4£^*p ^ »v..- % #^\ ™ m i» '■#> »» *r^* »'-.'•*,. tit ;i •* < ; ^hr )\))(V\ •i '.; .. V'.V Fig- 1. — Schematic illustration of a tubercle. Center, necrotic giant cell; second layer, epithelioid cells; outer layer, lymphocytes. (Adami.) Fig. 2. — Illustrating conversion of tubercle into scar tissue. Tubercle undergoing fibrosis; center partially fibrous. (Fowler and Godley.) b — m Fig 3 Illustrating conversion of tubercle into necrotic tissue. Tubercle undergoing caseation. A, caseous central area; B, cellular peripheral area; C-C , giant cells; D small- celled infiltration of surrounding alveolar walls and spaces; E, pigment. (Fowler and Godley.) 1 THE TUBERCLE 27 The collateral inflammation is due to substances which, passing out from the tubercle, diffuse into the tissues. These may be specific toxins, produced during the growth of the bacil- li, or substances of a fatty or albuminous nature which are de- rived from the destruction of the body of the bacillus. A large factor in the production of the inflammation is the presence of proteolytic enzymes. The inflammation is most severe near the tubercle and less so further away. Bacilli often pass from within the tubercles out into the tis- sues affected by collateral inflammation, and set up new foci of infection. These metastatic foci are more serious than the collateral inflammation alone. The tissues which are affected by the collateral inflammation are especially prone to infec- tion because the cells are injured by the exudative process and there is a stagnation of blood and lymph which prevents the free access of antibodies; and further lodgment of bacilli in the tissues is favored by the lessened motion of the part. Recognition of Tuberculous Inflammations. — Tuberculosis shows every form of inflammatory change; and while there are certain changes which are most often found in tuberculous tis- sue, yet there are none that are absolutely characteristic. Ex- udates in which lymphocytes predominate are considered to be of tuberculous nature, while those in which polynuclears pre- dominate are considered non-tuberculous. This will not always hold true. Polynuclear leucocytes sometimes predominate in the cerebrospinal fluid in tuberculous meningitis in the early stage of the disease; and lymphocytes may be found in large numbers in any chronic non-purulent exudate. Necrosis and cheesy degeneration are found in other inflammations as well as tuberculosis. Even the tubercle, as previously mentioned, with its giant cells may be found in other inflammations. Conglomerate Tubercle. — Large foci are often formed by a number of tubercles fusing together. Such conglomerate tuber- cles, as they are called, may be only as large as a small marble, or they may be as large as one's fist. Tuberculous Ulcer. — One of the common results of the tuber- culous inflammation is the tuberculous ulcer. This is a result of the degenerative changes in the tubercle; or, if large, in the 28 PATHOLOGICAL CHANGES IN TUBERCULOSIS conglomerate tubercle. As long as tubercle bacilli are capable of multiplying they give off toxic substances; and both during growth and after destruction yield substances belonging to the fatty and protein groups, which produce necrosis of the cells with which they come in contact. This softening of the tuber- culous mass is usually accompanied by an inflammatory process and a rupture of the walls confining it. If it is somewhere on the surface, such as in the larynx, or pharynx, a superficial ul- cer remains. If it is deep in the tissues, as in the lung, bone, or kidney, a rupture is followed by a loss of tissue, a cavity re- maining. All tuberculous ulcers and cavities are formed in the same way, first by a deposit of bacilli ; second, a softening of a mass of cells with a separation of the tissues, then a rupture, usually near the center. As a result it can be seen that the edges of a tuber- A B C Fig. 4. — Schematic illustration of the manner in which tuberculous ulcerations or cavities are formed. A, deposit of bacilli; B, necrosis of the mass; C, the rupture with expulsion of the contents. culous ulcer are undermined. This is illustrated schematically in Fig. 4, in which A represents implantation of bacilli and indu- ration of tissue ; B, softening of center ; C, rupture and expulsion of abscess contents with edges of surrounding tissue projecting beyond the abscess walls. A tuberculous cavity may be one single abscess cavity with regularly formed walls, or it may be irregular, the result of many adjoining abscesses. The walls may be smooth and regu- lar, or irregular. They may always secrete or they may even- tually dry out. They may always remain as open cavities or they may, especially when small, be compressed as contraction occurs, and be either partially or wholly closed. The walls of cavities when chronic, may be made up of fibrous tissue one or more centimeters in thickness. Cavities are often a source of bleeding. Sometimes the blood is scant, and is thoroughly mixed with pus from the cavity, giv- CAVITIES AND HEMORRHAGE 29 ing a pinkish appearance. This is, as a rule, from delicate new blood vessels. The most serious hemorrhages, however, often come from larger vessels in cavities. Where cavities form, the vessels, as a rule, are closed off by inflammatory changes in their walls, but now and then either the vessel is too large or the de- structive process in the tissues comes too rapidly and the con- tents are evacuated while the vessel still remains patulous. The supporting tissue being taken away from the walls of the ves- Fig. 5. — Illustrating schematically aneurismal dilatation of a vessel in a cavity, rupture of which often produces hemorrhage. sel, it dilates, forms an aneurism, becomes thinner and thinner, and eventually ruptures. In this manner many fatal hemor- rhages occur. This is illustrated in a schematic way by Fig. 5. Avenues of Infection. — There has been much discussion dur- ing recent years as to the modes of entry of the tubercle bacil- lus into the human body. Formerly it was taken for granted that it must be through the air passages because the lungs were usually involved. Later, entrance through the alimentary tract was proved, and this assumed a prominence which, for a time, 30 PATHOLOGICAL CHANGES IN TUBERCULOSIS completely overshadowed the route of the air passages. Animal experiments have been performed that show" that both routes are capable of carrying the bacilli to a safe lodgment in the tissues. They also enter through the skin, but this route is of comparatively little importance. Bacilli do not require injured mucous membranes to facili- tate their passage, but penetrate through the intact surfaces. Bacilli pass through the intestinal wall and may be carried to the liver, or lymphatic glands ; or, through the thoracic duct and pass directly into the blood stream. Bacilli injected into the rectum have been found within a few days in the mediastinal glands and lungs. Bacilli seem to find their way to the peri- bronchial glands no matter how they enter the body. Until this point was proved it was thought that infection must be nearly all aerogenous because of the frequent involvement of the lungs and bronchial glands. In 1912 Ghon 1 published the results of a painstaking post- mortem examination of chests of children having enlarged peri- bronchial glands and showed in every case where he found certain peribronchial glands infected that, by examining that portion of the lungs, whose lymph drained into these glands, he could demonstrate a tuberculous nodule. This work seems to substantiate the aerogenous theory; but when we recall that bacilli might be taken through the walls of the alimentary canal and be carried through the thoracic duct and poured into the blood which passes through the lung before passing on to the general circulation, we can see that even alimentary infection might produce foci in the lungs without primary involvement of the lymphatic glands. The route of entry is of practical importance in the solution of the question of the relative danger of bovine and human in- fection. The chief source of infection from cattle is milk; and the chief avenue of infection is through the alimentary tract. On the other hand, bacilli of human origin may be found in the air we breathe, especially in closed rooms occupied by open cases of tuberculosis living under unfavorable hygienic condi- tions ; in food we eat ; or in droplets of sputum thrown from the mouth of the coughing patient (Fliigge). So, human bacilli may x Der Primare Lungenherd bei der Tuberkulose der Kinder, Wien, 1912. LOCALIZATION OF TUBERCULOSIS 31 be taken into the body either through the air passages or the alimentary tract. No matter in which way they enter, the process is the same. While it is generally believed that nearly all cases of pulmon- ary tuberculosis in the human being are due to human tubercle bacilli, and that the extrapulmonary lesions are more apt to be due to bovine bacilli; this question is far from being proved, and cannot be decided on the basis of the routes of infection. Some have thought that the adaptability of the tissues to the particular strain might be a factor in localization, while the bacilli of both varieties gain entrance through the same avenues. Both types have equal advantage in gaining access to the lym- phatic system and probably follow much the same laws in their spread. Neither can it be determined by the severity of the process; for, as a general rule, the method of producing metas- tatic infection, has much to do with the virulence of the process. Processes which result from blood metastases, such as the early lesions in the lung, those in bones, joints and the kidneys are mild infections, while those which spread through the lymph chan- nels, such as the secondary metastases in tissues adjacent to other foci, and those which spread through the bronchi are apt to be serious infections. For a more complete discussion see page 57. The Localization of Tuberculosis. — No matter whether the bacilli gain entrance through the air passages or the gastro- intestinal tract their localization and further spreading in the body seems to take much the same course. Whether the bacilli gain entrance through the one tract or the other, they usually, eventually, in some manner, make their way to the lymphatic glands and very frequently to the peribronchial and peritracheal glands. The mesenteric glands may be infected when bacilli enter through the gastrointestinal tract, the same as the cervical when the tonsil is the point of entry; but, on the other hand, it is not necessary that such should be the case, for bacilli may be carried from the tonsils, intestinal walls or other mucous sur- faces to the lungs and mediastinal glands, leaving these regional glands in a healthy condition. The passage of bacilli through groups of glands is particularly apt to occur in childhood be- cause of the peculiar characteristics of the glandular structure 32 PATHOLOGICAL CHANGES IN TUBERCULOSIS in early life. Bartel 2 shows that the canals in the lymphatic gland of the child are wide, while those of the adult are narrow, thus permitting bacilli to pass on in the former, while they are detained in the latter. In the former bacilli may pass on through several glands before finding lodgment. Lack of specific cellu- lar defense must also be a factor in inoculations in early years. Even if the primary extraglandular focus should be some- where in the lungs, as has been shown by Ghon, the particular bronchial glands which drain the area also become infected, en- large and remain a nidus whence further metastases may occur. The primary focus is, as a rule, small. The glandular focus, on the other hand, even though secondary, is apt to be large and out of all proportion to the primary lesion. This is illustrated in Fig. 6, from Ghon's monograph. See further discussion in Chapter II. From the fact that the glands bear such a prominent part in early infections, tuberculosis must be looked upon as being primarily a disease of the lymphatic system which produces secondary or metastatic infections in almost any organ of the body, but which shows a marked predilection for the lungs. It might be suggested that one reason why the lungs are so often the seat of involvement in metastatic tuberculosis is be- cause the bacilli pass from the infected lymphatic glands into the blood vessels and are carried through the lesser circulatory system to the lungs before circulating in other parts of the body. But this theory leaves some phenomena still unexplained, especially since we know the bacilli are often found in the sys- temic circulation of patients suffering from tuberculosis (Rosen- berg), particularly advanced tuberculosis. We know no reason why we should not assume that the pulmonary tissue is particu- larly favorable to the growth of the tubercle bacillus the same as the tonsil is favorable to the diphtheria bacillus. Eosenow has shown that streptococci cultivated from the thy- roid localize preferably in the thyroid in experimental infec- tion; those grown in the tonsil, in the tonsil; and the same for bacteria from other tissues. It is quite reasonable to suppose that the same law operates in the localization of the tubercle 2 Der normale und abnormale Bau des Lymphatischen Systems und siene Beziehungen zur Tuberkulose; Festschrift zur VI Internationale!! Tuberkulosen Konferenz, Wien, 1907. Fig. 6. — Illustrating disproportion between lesion in the lung and the enlargement of the peribronchial glands in a child in whom immunity has not been established by previous infection. Primary caseous focus in the left upper lobe, with miliary tubercles in the surrounding area. Caseation of the bronchopulmonary lymphatic glands adjoining the left upper lobe, alongside of the partially visible dissected bronchus. Caseation of the upper tracheobronchial lymphatic glands on the left, and adhesion of these lymphatic glands with the medial surface of the left upper lobe. Acute miliary tubercles in the lower tracheo- bronchial lymphatic glands. Scattered acute miliary tubercles in both lungs. The upper tracheobronchial and bronchopulmonary lymphatic glands on the right are unaltered. The preparation was preserved in accordance with Kaiserling's method, and is taken from a four-year-old boy. Reduced photograph of the preparation. Posterior view. (Ghon.) AIR-BORNE AND BLOOD-BORNE INTRATHORACIC DISEASES 06 bacillus. It is in full harmony with our ideas that bacilli grown on a given medium assume peculiar characteristics and become more and more partial to that medium. We must still account for the fact that the apex is most of- ten the seat of infection. This question is discussed in Chapter V, and needs no further discussion at this time. Differences in Air-borne and Blood-borne Intrathoracic Dis- eases. — Bearing upon the question of the route of infection and the special predisposition of the apex to infection in tubercu- losis, important information can be gained by studying other infections of the lower respiratory tract. The special bacteria which produce the various pneumonias and infections of the bronchial tract are air-borne and often found in a saprophytic state in the air passages, particularly those of the upper respira- tory tract. These diseases may be localized in any portion of the lungs, but are particularly prone to infect those portions of the lung which receive the air currents most directly, and in which respiratory movement is greatest ; consequently the pneu- monias (lobar) most often affect the lower lobes; and, where other lobes are also involved, the disease usually makes its first appearance in the lower lobe. Bronchitis and bronchial pneu- monia may affect any portion of the lung or lungs ; but in bron- chitis, as a rule, the infection begins in the trachea and large bronchi where the parts are most exposed to the air currents and extends progressively toward the fine ramifications of the air passages. If the smaller tubes and air cells become involved, causing a bronchial pneumonia, it usually shows itself first at the bases, or, at least, over the lower portions of the lungs. Thus the common, definitely accepted air-borne diseases of the lungs affect the larger bronchi and the lower lobes, where the entrance of the air is most direct and the movements great- est; and we would expect tuberculosis, if it were an air-borne disease, to have the same localization. On the contrary, disre- garding lesions which spread contiguously from the hilus, the pulmonary involvement in tuberculosis, as we find it clinically and pathologically, usually affects first the apices of the lungs and then spreads downward involving contiguous or nearby tissue. This indicates a distinct difference in the mode of in- fection for bronchitis and pneumonia on the one hand and tu- 34 PATHOLOGICAL CHANGES IN TUBERCULOSIS berculosis on the other; and since we know that bacilli are car- ried to the lung, both by the blood and lymph streams, also along the paths of the bronchi in secondary metastases; and, since we also know that a slowing of the blood and lymph current takes place at the apices, favoring the deposit of bacilli in both blood and lymph channels, we are justified in suspecting the tubercle bacillus to follow one or both of these modes of gaining access to the pulmonary parenchyma. This indicates that pulmonary tuberculosis is metastatic tuberculosis, secondary to other foci. Since there is a wide gap between the primary focus in the gland (usually in the tracheal and peribronchial group) and the apex of the lung where the first pulmonary metastatic focus oc- curs, we must assume that it is far more probable that the metas- tasis is a result of infection in the direction of the natural cur- rents of the blood than that it should take place against the current of lymph which flows from the apex toward the hilus. The Effect of Cell Sensitization Upon the Implantation of Bacilli. — We cannot consider the train of events which takes place in the spreading of tuberculosis from the lymphatic sys- tem to other tissues, without at the same time considering the degree of immunity present in the patient's body and the im- munity reactions which occur between the tissues and the bacilli which have made their escape from the previous foci. We are probably justified in assuming, if we interpret experi- mental results correctly, that every patient who has an infec- tion of any portion of the body has struggled with the bacillus ; and while it may be that he has not been fully able to overcome it, yet he has at least developed a more or less marked immu- nity against it. And we must also believe that a more or less continuous inoculation, with its resultant immunization, goes on from this glandular focus until in favorable cases the bacilli cease to multiply and the focus heals ; and in less favorable con- ditions, although healing may not occur, yet the multiplication of bacilli is usually checked and the activity of the disease pro- cess held in abeyance for a time. The child, coming in contact with tubercle bacilli, usually meets them at first in small numbers, and is able to overcome them; or, at least to confine the infection to one of mild degree. Where an infection has resulted and been confined to a small CELL SENSITIZATION AND METASTASES 35 focus, whether this heals or not, the organism develops such a degree of immunity, that is, the cells develop such a power of specific defense that it is able to defend itself almost wholly from further infection from without. 3 Koch's original experiment showing that whereas a healthy guinea pig infected with tubercle bacilli, shows a ready absorption of the bacilli and an infection of the regional lymph glands, while one which was previously tuberculous, shows a resistance to infection, a local ulcer form- ing, the bacilli being expelled and the regional lymph glands re- maining unaffected, confirms this. Secondary, or metastatic infections, such as those affecting the lungs, are for the most part believed to be due to bacilli escaping from some previous, usually lymphatic, focus. Here, too, we must suppose that the number of bacilli escaping is usually small, and that most of them are destroyed without an infection occurring. The probabilities are that if they are not destroyed while coursing in the blood stream, they are reduced in virulence. Many of them, we assume, are destroyed as a re- sult of their stimulation of the sensitized cells to the produc- tion of specific protective ferments, as soon as they are enmeshed in the pulmonary tissues. However, now and then, regardless of the specific cellular defense (immunity) present, an infection will occur. This metastatic focus, as a rule, is small and single ; the exception being when a large number of bacilli have made their escape from the lymphatic focus, such as occurs when soft- ening of a large tubercle takes place with rupture into a blood vessel, producing either a localized or a general dissemination (miliary tuberculosis). The body fluids containing antibodies, the pulmonary cells being specifically sensitized and the number of invading bacilli being small, the early metastases, as a rule, do not make rapid progress. They are fibroid in form. They often amount to no more than a nodule which can be found only by most careful search; at times, however, the infection is more widespread and yet results in new tissue formation. Occasionally, however, the primary metastasis will be transformed into an area of necrosis, either small or large, which may either become calcified and re- main quiescent, or rupture, leaving an open ulcerating surface, 8 Romer: Brauer's Beitrage zur Tuberkulose, Bd. xiii, xvii, and xxii. 36 PATHOLOGICAL. CHANGES IN TUBERCULOSIS this again to heal or remain as a focus from which further metastases may form. These primary foci in the lung often become encapsulated with bacilli enclosed; and, while the bacilli may go on to death, yet at times they remain alive and sooner or later, for some cause which we do not understand, begin to multiply and produce ac- tivity in the focus of infection. Von Pirquet has assumed that at times the body takes upon itself a condition wherein, tem- porarily, it loses its specific defense against bacilli, and in this way he accounts for the renewed activity in old quiescent foci. This condition has been termed "anergie" by him. Any focus which has not thoroughly healed with destruction of the bacilli, may be a source of further dissemination of the disease. From these primary metastatic foci the disease may spread at once or later, either by way of adjacent lymph spaces or small bronchi; pushing out into the adjoining tissues and gradually involving more and more of the lung. The extension usually takes place downward from the apex. Should the bacilli gain access to the blood stream, metastasis may occur in distant portions of the lungs or even distant parts of the body. But the general rule is for tuberculosis to extend contiguously. The first pulmonary metastasis of hemotogenous origin usually occurs near the apex, nearly always above the third rib. This is the same area that usually shows infection of the pleura. Aside from these areas there is often a primary infection of those pulmonary and pleural tissues which are contiguous to the bronchial glands, the infection apparently extending against the lymph stream into the tissue. Lymphogenous Metastasis. — The spreading of pulmonary tuber- culosis through the lymphatics is of special import. It is prob- able that bacilli are carried by the wandering cells. Some au- thors attribute great importance to this method of spread. Again, it may spread through the lymph spaces. In this con- nection it is necessary to understand the influence of respira- tion in both the healthy and diseased lung. Every inspiration increases the pulmonary area and widens the intrapulmonary lymph spaces; every expiration lessens the pulmonary area and narrows the lymph spaces. By this succession of enlarging and narrowing the lymph spaces, the fluid is moved back and forth LYMPHOGENOUS AND BRONCHOGENOUS METASTASES 37 through the pulmonary tissues. Not only is the lymph forced toward the larger lymphatic trunks and regional glands, but it can easily be seen that it might be forced backwards as well. This occurs often; and it is now generally conceded that bacilli may be forced onward in the general direction of the lymph flow or backward against the stream (Tendeloo). Another point of great interest is that there is a wide difference in the lymph flow in various portions of the lungs, also in the healthy as compared with the tuberculous lung. The motion of the chest wall and diaphragm is lessened on the affected side. The respiratory ef- fort is restricted and consequently the flow of lymph is retarded throughout the organ, a condition which favors the implanta- tion of bacilli in the lymph spaces. Lymphatic metastases are often found in the glands of the lung, the lymph spaces surrounding the bronchi and vessels and the subpleural spaees. The fact that tubercle bacilli may be carried against the lymph stream assumes special importance in connection with the theory of certain authors that infection travels from the hilus toward the apex. The conditions which favor lymphatic metastases are the col- lateral inflammation and the restricted motion of the part. These are accompanied by injury of the tissue and a retarded lymph flow. If only a few bacilli escape into the adjacent lymph spaces the resulting infection may be mild, but, if the numbers are great the best conditions possible are present for an extreme- ly virulent metastasis. Bronchogenous Metastasis. — While the lessened motion of the diseased lung together with the stasis dependent upon the col- lateral inflammation favor lymphatic spread of the disease, it lessens the danger of spread by the bronchi. This latter is a very common form of spreading of the disease in open dases. When the disease has passed to the point of softening and cav- ity formation, the air passages are always exposed to the danger of infection from this source. Deep breathing and coughing has a tendency to force the bacillus-bearing sputum into areas not already infected, to plug the bronchus with infectious mucus, thus starting up new foci of infection. When bacilli are im- planted upon the tissues through the bronchial route, they do 38 PATHOLOGICAL CHANGES IN TUBERCULOSIS not affect the epithelium of the air passages, but pass through the mucous membrane and settle in the subepithelial cells. This type of the disease is apt to be very virulent. This is the usual method of infection in circumscribed caseous pneumonias. Hematogenous Metastasis. — Hematogenous metastasis shows many variations. It has been proved recently that tuberculosis is at times a bacillemia. Bacilli often pass into the blood stream ; and they can be recovered in a large per cent of patients suf- fering from the advanced form of the disease. When only a few bacilli enter the blood stream, they are destroyed without an in- fection resulting; when the number is larger they may with- stand the effects of the antibacillary elements in the blood, like- wise the specific defensive properties of the cells in which im- plantation occurs and form a new focus; when still larger the bacilli may be in such numbers that they heap up, blocking the capillaries of either a particular, limited area supplied by a certain small blood vessel and its branches or of a large area of the body supplied by a very large vessel, causing acute gen- eral miliary tuberculosis. The hematogenous form of spreading accounts for the infec- tion of an organ distant from the primary focus. Thus, such lesions as those of the bones, joints, meninges, and kidneys oc- cur when the primary focus is in the mediastinal glands or lung. Ordinarily, except in acute miliary tuberculosis, the lesions which are caused by spreading through the blood are of a mild, non-virulent type. This is probably due to the fact that bacil- li, entering the blood stream, come in contact with the specific antibacillary substances so intimately that while not wholly de- stroyed, their virulence is greatly reduced, and, further, they are so scattered by the flowing blood that the infection which occurs is formed by few bacilli. Widespread fibroid tuberculosis is produced in this same manner. There has been much speculation on the part of students of tuberculosis in trying to explain why the areas above the third rib, and particularly those toward the vertebrae, are more prone to infection than other portions of the lung. The plausible ex- planation is that these areas naturally have less motion than other parts of the lung, consequently, have a comparative retard- ing effect on the blood and lymph flow which, in turn, favors the Fig. 7. — Miliary tuberculosis of the lung. (Tendeloo.) LOCALIZATION OF PULMONARY TUBERCULOSIS 39 heaping up of bacilli in the capillaries and lymph spaces, thus favoring infection. If, however, it were the lessened motion alone which favors infection, the disease would be most com- mon at or near the hilus for it is at that point that the lung shows the least motion; but implantation is not favored at this point, either by way of the lymph or blood because the lymphatic trunks are larger and the capillary network is not as extensive as in the apex. It does occur, however, at times, as is shown by x-ray examination. Freund, Schmorl and Rothschild have found certain conditions about the upper aperture of the thorax which they have de- scribed as being causative factors in the production of tubercu- losis. Freund has found a shortening of the first rib and ossifi- cation of the first costal cartilage in many cases of tuberculosis and believes that these conditions act mechanically. This has been strongly supported by Hart. Schmorl has described fur- rows near the apex which he believes retard the flow of lymph and blood. Rothschild has found that there is a diminution of action in the manubrio-sternal joint in tuberculosis and described it as a predisposing cause. These theories fail to take certain facts into consideration. If the compression of the rib, or the furrow, or the lack of motion of the manubrio-sternal joint were the particular predisposing causes of underlying tuberculosis of the apex, we would expect the disease to begin in that portion of the lung most affected by such compression, namely, the an- terior surface; but such is not the case. The disease usually begins posteriorly and near the vertebral column. Aside from this failure to conform to the facts of the localization of the disease, a more plausible explanation can be offered depending upon the anatomical differences incident to development and growth. In this connection I would refer the reader to Chap- ter V which treats of this subject more fully. Forms of Tuberculosis. — Tuberculosis presents many differ- ent clinical pictures but there is no particular advantage in treating each as a separate entity. Pathologically we may classify the disease into those forms which have a tendency to produce new tissue, those in which destruction of tissue is the predominant factor, and the combination of these two. Miliary Tuberculosis. — Miliary tuberculosis (Fig. 7), as previ- 40 PATHOLOGICAL CHANGES IN TUBERCULOSIS ously mentioned, is caused by bacilli being thrown into the blood or lymph stream in large numbers. It is characterized by new tissue formation. There may be a large or small area in- volved. The tubercles throughout the area infected are of the same age and size having come from the same inoculation. Mili- ary tuberculosis may affect any organ. We see it in the lungs, spleen, liver, kidney, meninges, and peritoneum. If extensive, or if it affects a vital organ it is usually fatal in a short time. It may be generalized and affect many organs. One patient un- der my care, with miliary disease of the lungs, died on the twenty-first day after the onset of symptoms. Miliary disease of the lung often produces death before the tubercles soften. It may be a primary metastatic disease coming from some caseous focus in a patient who has been previously healthy, and ap- parently free from disease; or it may follow the breaking of a necrotic mass into the blood stream in chronic tuberculosis. I have seen it follow hemorrhages in a number of instances, suf- ficient bacilli gaining access to the blood stream to cause a gen- eralized miliary condition and a rapidly fatal issue. Fibroid Tuberculosis. — Fibroid tuberculosis is another form of the disease characterized pathologically by the formation of new tissue. This disease is usually chronic in character being produced by bacilli of low virulence. It is of hematogenous origin and the low virulence may be due to the fact that the bacilli are diluted, that their virulence has been reduced by the antibodies with which they have come in contact in the blood stream and the fact that the cells are endowed with the property of producing specific defensive enzymes before inocu- lation has occurred, as previously mentioned. The primary metastatic focus in nearly all organs is small in extent and fibroid in character, regardless of the form which the disease may assume later. The virulence of the infecting bacilli in fibroid tuberculosis is so low that a very small amount of toxins are thrown out, con- sequently the tissues are irritated but not destroyed. This type is accompanied by a very mild collateral inflammation. The production of new granulation tissue results (Fig. 8). Some- times this is very rich in blood vessels and results in large bundles of new tissue which later on are converted into hard Fig. 8. — Illustrating pulmonary tuberculosis, with thickened pleura, many bronchiectatic cavities, and generalized cavity formation. (Tendeloo.) Fig. 9. — Sacculated bronchiectasis. (Powell and Hartley.) TYPES OF TUBERCULOSIS 41 scar which contracts and if extensive causes a great deformity of the organ. Resulting from the extensive contraction the lung becomes smaller. In order to compensate for the loss on the part of the affected lung, the other lung and the portions of the same lung which are not affected by the fibrosis, become emphysematous, the mediastinum draws toward the contracted side and all the thoracic organs are compelled to adjust them- selves to new conditions, as described fully in Chapter XI. Pouching of the bronchi may take place as a result of the ir- regular contraction causing a condition of bronchiectasis (Figs. 8 and 9). This form of tuberculosis is accompanied by extensive connec- tive tissue formation and the bacilli are well walled in. Many of them die. Others remain living but are rendered harmless. After a time, for some unexplainable reason, bacilli which have been shut up in the scar tissue and which have remained in a state of inactivity may develop an increased virulence. They multiply, produce toxins which are followed by necrosis and the conversion of the process into an ulcerative one. This is the course which many of the fibroid lungs eventually follow. Caseous Tuberculosis. — Caseous tuberculosis (Fig. 10), is that form of the disease in which degenerative processes predomi- nate. This form presupposes a virulent strain of bacilli and bio- chemical conditions of the tissues favorable to their rapid mul- tiplication. These conditions result in a rapid development of toxins, with extensive necrosis, and a wide spread severe collat- eral inflammation. Acute tuberculosis, the so-called "gallop- ing consumption," and acute pneumonic tuberculosis are of this type. These forms of the disease are characterized patho- logically by rapid destruction of tissue with cavity formation if the patient lives long enough and little or no tendency to con- nective tissue formation. If the process is extensive, marked toxemia and such a state of malnutrition accompanied by de- generative changes in the various organs occurs that the patient soon succumbs. If, on the other hand, the process is confined to a lobe or a portion of a lobe, the necrotic tissues may be ex- pelled, a cavity resulting with relief of the toxemia and improve- ment of the patient. This is not an uncommon result. Fibro-Caseous Tuberculosis. — This is the most common type of 42 PATHOLOGICAL CHANGES IN TUBERCULOSIS pulmonary tuberculosis met clinically. It is the usual form of chronic clinical tuberculosis. It consists of areas of necrosis which rupture and are thrown off leaving cavities; a collateral inflammation of a moderate degree; and a tendency to the pro- duction of new tissue in the areas which are the seat of tuber- cles which have not yet gone on to necrosis and softening; and further, a tendency to the formation of connective tissues about the walls of the cavities. In some patients the necrosis and ul- cerative process predominates; in others the fibrosis. The process is chronic, and when progressive, gradually spreads from the apex downward toward the bases of the lungs. The great- est number of cavities is usually near the apex. Another fav- ored seat is the apex of the lower lobe, although any portion of the lungs may be the seat of cavity. Cavities at the apices of the lungs are much more favorable for healing than those in the lower lobes because they are kept clean with greater ease, drainage being in their favor. The prognosis of this type de- pends much on the extent of the lesion and as to whether ul- ceration or fibrosis predominates. Sometimes an ulcerative process will predominate at first and fibrosis later, which usually means a retardation or an arrestment of the process ; sometimes the reverse is true, which means progression and ultimate loss of life. This form of tuberculosis, if an arrestment occurs, often shows even more marked contraction and compensatory changes with greater shifting of the mediastinum and diaphragm than the more purely fibroid form. Non-tuberculous Changes in Other Organs. — In chronic pul- monary tuberculosis there are changes in the various organs of a non-tuberculous character which prove to be extremely important from the standpoint of prognosis, and which must not be neglected in therapy. Pulmonary tuberculosis, after it has reached the chronic stage (consumption) cannot be looked upon as merely a disease of the lungs. It is a disease of the lungs caused by the im- plantation of the tubercle bacillus, plus all secondary changes resulting from and accompanying such infection; plus all the disturbances of function on the part of the other organs of the body which result from the changes in the lungs and from the Fig. 10.— Illustrating caseous tuberculosis. Large cavities at the apex and many small cavities throughout the lung. (Tendeloo.) NON-TUBERCULOUS DEGENERATIONS 43 specific toxemia and the malnutrition which, accompany the disease. Degeneration. — There are three degenerative changes which are commonly found in the bodies of those who die from chronic ulcerative tuberculosis, amyloid, fatty, and cloudy swelling. These three forms of degeneration involve different tissues, but in their selection leave few if any tissues unaffected. These degenerations are usually explained as being due to the effect of toxins and malnutrition. Just how these factors act is not perfectly clear. Our knowledge of the degenerations of the structures which are affected by reflex stimulation as il- lustrated in the regional degeneration of the skin, subcutaneous tissue and muscles, offers a basis for thinking that probably the same degenerative tendency might be found wherever tissues stand in a relationship to be affected reflexly by impulses cours- ing from the lung. If so, then we are led to the conclusion that all organs which stand in such a relationship with the pulmon- ary branches of the vagus and possibly also of the sympathetic divisions of the vegetative system might be so affected. Further, realizing that toxins stimulate the sympathetics centrally, we have a double stimulation of this division which tends to produce the same effect. In this connection, the studies of Crile 4 show that continuous stimulation of nerves by such stimuli as depressive emo- tional states, pain and toxemias, produce changes in the higher center. It seems that the way is now open so that we may go a step further than to say that toxemias and malnutrition are the causes of degenerations; and suggest that the cause which oper- ates to produce them, acts, at least partially, through the vege- tative nervous system. To this we must also add the possibility of degeneration resulting from changes coming from the chem- ical stimuli which are produced by altered internal secretions. The work of Fisher in showing that the equilibrium which main- tains tissue stability is easily changed, suggests this as an im- portant factor. Amyloid Degeneration. — Amyloid degeneration, or waxy de- generation as it is called, affects connective tissue and blood vessels. By a gradual change the small arteries and capillaries are involved; their walls are thickened and later become obliter- •••-*--- — ,,^ v , , ?S8Rj$^WS£ 2nd Rib Apex of lung, -•- ~~"v£r?C£vJw^ 1st rib (inspir.) .-... - — V(^>'< 1 ' >£bi(p ' \\\VS_v 1st rib (expir.),... ... - J x^- i \}rtf8^\v\\\\w^ Manub. (inspir.) .„ . /"Vo^rfmrrtf""^^ Manub. (expir.) yv:^iwNM\>M^ i TiT^J^V^vV 1st man jt. 1st man jt. Lung (inspir.) I/O Fig. 23. — Illustrating the action of the first pair of ribs and manubrium in increasing the area of the lung during inspiration. Showing that the posterior aspect of the apex is the portion subjected to least movement. (Keith.) fection, while the apex of the adult lung is so predisposed. The solution of the problem may be aided by studying the anatomic and physiologic changes in the chest during the period of growth, and by studying the action of the inhaled dust at the various age periods, as previously mentioned. To repeat the important facts mentioned elsewhere in these pages, if the child inspires air contaminated with dust or soot the particles do not lodge in the pulmonary tissues but pass through to the subpleural lymph spaces, and more particularly to the peribronchial lymph glands. In other words, they follow "Further Advances in Physiology, Edit, by Leonard Hill, 1909. FACTORS FAVORING APICAL INFECTION 135 the course of the lymph in the lymphatic channels. In the adult lung, on the other hand, much dust and soot is deposited in the lung tissue itself, and in the subpleural spaces, while the bronchial glands are less affected. It is further observed, in the adult lung, that dust and soot are deposited particularly in the apex of the lung, while the base is comparatively free. It has been suggested that the reason for the marked deposit of soot in the lung tissue in the adult is because, through pro- tracted exposure, more and more particles have become deposited in the lymph spaces and that these retard the progress of others taken in later. It has also been thought that there is more or less irritation and thickening of the lung tissue caused by the dust particles which prevent their rapid transfer to the lymph glands. Some have suggested that these deposits in the tissues pet as a predisposing cause to the localization of the tubercle bacillus. Tendeloo particularly, has insisted that the principal factor in predisposing the apex to tuberculosis is the fact that there is a lessened motion of the lung in this area and consequently a retarded lymph and blood flow. This is shown in Figs. 20, 21, 22, and 23. This is a very important consideration in any theory that is offered. Its effect can be seen in the distribution of the deposits of dust and soot in the lung of the child as compared with the lung of the adult, and its influence on the implanta- tion of tubercle bacilli must be equally important. Critical Examination of Theories of Freund, Schmorl and Rothschild. — I have endeavored to offer an anatomic and physi- ologic explanation for the fact that the apex of the lung of the adult is predisposed to infection, but I now wish to take up the matter at this point and discuss! it in relationship to Freund 's theory, which has received so much attention during recent years. With Freund 's theory we must also class the theories of Schmorl, 8 Birch-Hirschfeld 9 and Rothschild 10 because they are all closely related. 8 Zur Frage der beginnenden Lungentuberkulose, Mtinchener medicinische Wochen- schrift, 1901, No. SO. 9 Birch-Hirschfeld: tiber den Sitz und die Entwicklung der primaren Lungentuber- kulose, Deutsches Archiv fur klinische Medicin, Bd. 64, 1899; Ibid., Des erste Stadium der Lungenschwindsucht, Bericht Tuberkulosekongress, 1899. 10 Ober die physiologische und pathologische Bedeutung des sternalkinkels, XVIII Kon- gress fur inner Medicin, Karlsbad, 1899. 136 FACTORS WHICH PREDISPOSE TO TUBERCULOSIS Freund 11 published his first articles with reference to anomalies of the upper aperture of the thorax as factors in the causation of tuberculosis in 1858 and 1859, but his theories were unnoticed for forty years. No interest was taken in them until Birch- Hirschfeld published his paper with reference to the peculiar- ities of the post apical bronchus and its relationship to tubercu- losis and Schmorl brought out the idea of the bronchi being com- pressed by the furrows, which are produced by the upper ribs encroaching upon the lung. It was then that Freund 12 himself revived his previously sug- gested theories and with the aid of his pupils made for them a prominent place in the literature of tuberculosis. These publications created new interest in the anatomo- pathologic conditions surrounding the apex of the lung which during recent years have assumed great importance in the dis- cussion of the question as to why the apex of the lung is pre- disposed to tuberculosis. The discussion of this subject by Hart 13 and by Hart and Har- rass, 14 and Bacmeister 15 are extremely important and set forth in a clear manner the arguments in favor of these predisposing factors. As representing Hart's most recent discussion I will translate a quotation from his article in Bei-heft No. 11, zur Medizinischen Klinik, 1912, as given by Martius 16 in a recent discussion of this subject. " 'The upper aperture of the thorax which is formed by the first ribs and vertebra and sternum is heart-shaped in form. On either side of the vertebra are the apices of the lungs .which are surrounded by the bony portions of the first ribs. The costal ring departs from the horizontal in such a way that while the apices of the lungs are about on a level with the junction of the u Beitrage zur Histologic der Rippenknorpel in normalen und pathologischen Zus- tanden, Breslau, 1858; also Der Zusammenhang gewisser Eungenkrankheiten mit pri- maren Rippenknorpelanomalien, Erlangen, 1859. ^Thoraxanomalien als Predisposition zur Lungenphtliise und Emphysem, Verhand- lungen des Berliner medizinische Gesellschaft, Nov. 27, 1901. 13 Die mechanische Disposition der Eungenspitzen zur Tuberkulosen Phthise, Stuttgart, 1906. 14 Der Thorax phthisicus, eine anatomisch-physiologische Studie, Stuttgart, 1908. 15 Entstehung und Verhuetung der Eungenspitzen Tuberkulose, Deutsche medizinische Wochenschrift, 1911, Nr. 30. 16 Handbuch der Tuberkulose, Brauer, Schroder und Blumenfeld, vol. i, 1914, p. 409. EFFECT OF FIRST COSTAL RING ON RESPIRATION 137 first rib with the vertebra, the anterior end of the first rib is 2]/ 2 cm. below the apex. In contrast to all of the other true ribs we find that the first costal cartilage has no articulation with the sternum. In its place there is a short broad cartilaginous con- nection, whose union is made secure by the special firm consist- ency of the cartilage. On inspiration the cartilage takes upon itself a spiral action of such a nature that the motion produces a strong tension, the release of which permits, or mechanically forces the costal rings to return to the position of expiration. The first costal ring itself is elevated during inspiration, its position approaching the horizontal, but it produces no widen- ing of the upper aperture. On forced inspiration, even, the respiratory movement of the upper aperture is also relatively small in comparison with that of the remaining ribs, which gradually increases toward the base and whose elevation and elastic expiratory motion is favored by their free articulation with the vertebrae, their long elastic cartilages, as well as their articulation with the sternum; yet, in spite of this the function of the first costal ring is of much greater importance in the respiratory movement than that of all the others. " 'The respiratory motion of the lungs is regulated by a law which has been suggested by Tendeloo, that every portion of the lung is dependent functionally upon that portion of the thorax overlying it. According to this, while distension of single por- tions of the lung is of influence upon the amount of the entire volume of respiratory air, compensatory balances for local loss taking place, one portion of a lung is never able to influence the functional activity of a distant portion in such a way that the movement of the lung tissue in all places is uniformly the same. The alveoli of the apices of the lung are, in a general physiologic sense dilated to a lesser degree during inspiration; and the total pulmonary tissue experiences a weaker expansion than is the case in the remaining portions of the lung. Only by a forced pronounced costal breathing does the lung apex show a strong respiratory motion. By adjusting respiration to the minimum demand of oxygen, as in the usual moderately shallow thoracic breathing, a complete filling of the apices of the lungs seldom 138 FACTORS WHICH PREDISPOSE TO TUBERCULOSIS takes place; consequently, under normal conditions, the respira- tory motion of the upper part of the lung, when compared to the lower portion of the lung, that is, the prevailing relative func- tional activity, is decidedly small, as has been shown by Riegel. ' "Under normal physiologic conditions, this aeration is suf- ficient, but, under pathologic conditions, it is different. " 'The important fact of our new teaching is that in almost every adult person suffering from tuberculosis there is an an- atomical departure from the normal in the upper aperture of the thorax. At one time this takes the form of abnormal shorten- ing of the cartilage as described by Freund; again, in an ar- rested development of malformation of the bony portions of the rib ; and, still again, in a combination of both of these condi- tions. Sometimes the changes are symmetrical and sometimes asymmetrical, but always produce the same effect, differing on- ly in degree; namely, the transformation of the aperture from the oval heart-shaped form into a more long oval form, as is the type in animals and in man during the fetal stage. In the formation of this pathological aperture the ribs do not run in a gentle curve, but more directly forward to the sternum, conse- quently, the transverse diameter is shortened; but, what is of paramount importance, there is present a greater or lesser eon- traction of the posterior para-vertebral areas in which the apices of the lungs lie and move. " 'The upper costal ring which shows these pathological changes can only be considered as a whole and in its relation- ship to the entire thorax. One must recognize that not only its pathological configuration, but the degree of narrowing of the superior aperture of the thorax is extremely variable, and also that it depends somewhat upon the condition of the neighbor- ing parts (vertebra). He must also see that the anatomical changes of form and changes of position of the aperture and its relationship to the expansion of the apices emphasizes any anatomic functional disturbances that might be present. This disproportion produces a permanent pressure upon the pulmon- ary tissue of the apex. The consequence of this continuous pres- sure of the narrow and immobile costal ring, which is elevated only a little or not at all through the respiratory motion, is an injury of the lung tissue which is thus encircled. This makes ANOMALIES OF SUPERIOR THORACIC APERTURE 139 itself manifest subapically by means of a very marked furrow in which the ribs lie. In the interior of the lung, however, the small bronchi are compressed in such a manner that the apical bronchial systems give one the impression of being stunted in growth. Whoever has seen these two changes which Schmorl and Birch-Hirschfeld first considered worthy of description, must be completely convinced of their dependence upon the changes in the first costal ring. Whoever opposes this has never seen these changes in the pulmonary apices and forgets that in a large material of thousands of autopsies only an accident could bring it before one 's eyes, even though he were continually look- ing for it, because primary tuberculosis quickly destroys the original anatomical relations. " 'What we must conclude from these positive anatomical facts is plain. The mechanical functional disturbance of the upper aperture of the thorax leads to an interference with the ventilation of the apical tissue, and, secondarily, to an embar- rassment of the blood and lymph flow, both of which are, in a large measure, dependent upon the respiratory movement of the pulmonary tissue. The interference with the ventilation of the apices is not only logically explained by the functional depend- ence of the pulmonary apices upon the respiratory movements of the upper aperture of the thorax, and the specially unfavor- able conditions which result during quiet respiration from the peculiar course of the apical bronchi; but can also be directly proved upon the living through shadows indicative of thicken- ing of the tissues shown rontgenologically, which indicates partial or complete atelectasis or a later stage of collapse in- duration, and also on the cadaver by an increased deposit of carbon in the apical tissues. " 'Arnold has experimentally shown, and it is likewise a com- mon postmortem experience, that foreign particles are usually lodged in the neighborhood of thickenings in the tissues, also in the tissues which do not take full part in the respiratory move- ment. I (Hart) have especially called attention to the fact that the initial tuberculous apical lesion does not correspond, as a rule, to the sub-apical pressure furrow and the costal ring, but occurs in the tissues which are partially atelectatic. " 'From a physical standpoint the likelihood of tubercle bacilli 140 FACTORS WHICH PREDISPOSE TO TUBERCULOSIS settling in the apical tissues is also increased by the aperture anomalies. The reason that the bacilli are able to exercise their specific injurious influence is because of the increase of the bio- chemical susceptibility in the tissues, in consequence of the dis- turbance in the blood and lymph circulation which causes them to lose their natural resistance to the tubercle bacillus in conse- quence of poor nutrition. That such a thing exists no one can doubt who recognizes that almost every man comes in contact sometime with tubercle bacilli, and that they penetrate into the lung, usually in comparatively small numbers, nevertheless he becomes ill and suffers either from progressive tuberculosis or from some of the less virulent forms of infection. It has also been shown that the farther the upper aperture departs from the normal the quicker the process in the pulmonary apex spreads after infection has occurred, and the more rapid does it spread. On the other hand, the susceptibility of the tubercle virus, the individual disposition, is the same without reference to the way the bacillus enters the body, whether by the air, the blood or lymph passages. The physical opportunity and the biochemical susceptibility is the same. Aside from this the conditions under which the tuberculous process spreads in the inferior portions of the lung and in other organs has nothing to do with the ques- tion of disposition.' " Martius asks the question: how is this theory to be harmon- ized with the work of Ghon which shows that in children the apex does not show a special disposition to tuberculosis? And answers it by quoting from Hart as follows: "In children the fixation of the upper thoracic aperture, which is the result of a gradual development, has not yet taken place. "With the completion of the growth of the body, every func- tional disproportion between the development of the thoracic aperture and the development of the pulmonary apex becomes exaggerated, and of greater importance the wider the departure from the normal. At this time both the physical conditions and the biological susceptibility favor the implantation and growth of the bacillus no matter when or in what manner it enters. The morbidity from tuberculosis increases with great sudden- ness (explosionartig) at the end of the second and beginning of the third decade and the disease does not heal but goes on CRITICISM OF FREUND'S THEORY 141 making an almost continuous selection from all of those who are predisposed. Now and then someone will escape infection with the tubercle bacillus and its consequences; some, by pos- sessing relatively favorable conditions in the pulmonary tissue are enabled to develop a resistance to the enemy, which lasts for a long time, probably through life ; in all severe cases, how- ever, the battle is decided and the fate of the individual sealed from the beginning." The weak point in these theories lies in failing to grasp that any compression caused by a primarily shortened rib or nar- rowed aperture or changed manubrio-sternal angle, is only a part of the general compression which occurs in the upper por- tion of the thorax in the adult, as compared to the child, thus basing infection of the apex upon anomalies instead of natural anatomic and physiologic factors. There should be added to this excellent recent description given by Hart, some of the ideas which were originally enunciated by Freund, which are not here mentioned. In Freund 's 17 early description in discussing the ankylosed rib, he particularly calls attention to the altered condition of scaleni muscles in the following language: "In many patients who are suffering from beginning chronic tuberculosis of the apex of the lungs, one finds pathological changes, especially in the first costal cartilage, this change being an ossification. The bony change does not proceed from an inflammation of the pleura, for it usually begins first on the edges, then on the outer surface of the rib, and at last on the inner surface, and all takes place without the pleura being changed. This also occurs in beginning tuberculosis where the pleura is not yet involved. Under these conditions one always sees strong antagonistic development of the scaleni whose point of insertion on the rib often shows an exceptional size." My recent clinical observations 18 on the presence of reflexes caused by inflammation within the lungs shows that these mus- cles are thrown into definite contraction (spasm) reflexly from 17 Beitrage zur Histologie der Rippenknorpel in normalen und pathologischen Zus- tanden, Breslau, 1858, quoted by Hart. 18 Muscle Spasm and Degeneration in Intrathoracic Inflammations and Light Touch Palpation, C. V. Mosby Co., St. Louis, 1912; and Inspektion, Palpation, Perkussion and Auskultation bei der Fruhdiagnose der Lungentuberkulo.se, Brauer's Beitrage zur Klinik Tuberkulose, vol. xxxiii, part 1, 1915. 142 FACTORS WHICH PREDISPOSE TO TUBERCULOSIS the disease within the lung, and that what Freund described here was not hypertrophy due to muscles pulling against an anky- losed rib, but a reflex contraction due to the pulmonary inflammation. It is further necessary to bear in mind that we have sensory, motor and trophic reflexes dependent upon this pulmonary ir- ritation. As evidences of the trophic reflex we have the follow- ing phenomena: wasting of the skin, subcutaneous tissue and muscles, and dry arthritis of the joints, particularly the shoul- der joint. Knowing that the bony structures and the joints are supplied by the same nerves as the tissues over them (Piersol) we are justified in drawing the inference that trophic disturb- ances might also show in the bones and cartilages. While short- ening of the first rib in some cases might be congenital or might be due to some early disease of the bone or cartilage, interfer- ing with its proper development; yet we must not lose sight of the trophic disturbance which could be exerted reflexly upon these structures by inflammation within the thorax, particularly of the lungs. It is extremely suggestive in this connection that Hart should say: 19 "Freund attempted to carry this in- terference with the development of the first costal cartilage back to the time of childhood, even to the fetal epoch, but I, person- ally, have in no case, either in a child or in a fetus been able to find unquestionable symmetrical shortening of the first costal cartilage as a result of some prenatal interference with nutri- tion of the bone and cartilage." That tuberculous infection has a decided reflex trophic influence on these structures we know from clinical experience and are led to infer from the analysis of Hart's own statistics; and, that it could cause ankylosis of the first costosternal articulation by reflex trophic action and the diminished motion which follows infection is quite clear. At this point I desire to quote from papers by Stiller, Schiele, and Eevesz, because they have important bearing upon the re- lationship of compression of the upper aperture of the thorax to tuberculosis, also upon the relationship between calcification of the first costal cartilage and the tuberculous infection. Stiller 20 questions the importance of the thorax phthisicus as 19 loc. cit. 20 Der tuberkulose Thorax phthisicus und die tuberkulose Disposition, Berliner klinische Wochenschrift, 1912, No. 3. CRITICISM OF FREUND'S THEORY 143 being a predisposing cause of tuberculosis and also claims that the anomalies of the upper aperture of the thorax are identical with his thorax asthenicus. He does not consider that the early ossification of the first costal cartilage upon which Freund and Hart lay so much weight is more than one factor among many. Schiele 21 lays particular stress upon the degree to which the rib departs from the horizontal, claiming that the greater the angle of departure of the upper aperture in asthenic individuals, the greater the interference with the function of the organs within. He looks upon the early ossification of the first costal cartilage as not being a cause but a consequence of apical tuber- culosis and considers that it is due to a diminution of the in- tensity of the respiratory movement. He says that thorax phthisicus is not inherited but developed after birth. Revesz 22 reports the examination of 22 individuals with marked thorax asthenicus (Stiller) and found, according to the method of Harris, a shortening of the firsts costal cartilage in every in- stance. For controls he examined 11 people with normal chests and did not find a shortening of the first rib in a single instance. In 22 asthenic individuals he found only 4 in whom there was no trace of tuberculosis. In these 4 there was also no ossification in the first costal cartilage in a single instance. In 7 of the re- maining 18 who had a tuberculous infection, the apex of the lung was normal, the infection being in the peribronchial glands. In these 7 cases ossification of the first costal cartilage was also wanting. In the remaining 11 cases which showed pulmonary tuberculosis radiologically, calcification of the first costal car- tilage was found, therefore Revesz draws the conclusion that it is not the asthenia but the tuberculosis which produces the calci- fication in the costal cartilage and that this is not a predisposing cause but a result of tuberculosis. He further states that there was no evidence of ossification in the first costal cartilage in any of the 11 controls, and, further, that ossification of the firsl costal cartilage has not been found in a single instance in the Roentgen Institute of the University of Budapest in a young 21 Die Neigung der oberen Thoraxapertur, Zeitschrift fur klinische Medicin, 1912, vol. lxxvi, parts 5 and 6. 22 Thoraxphthisicus und Thorax asthenicus, Gyogyaszat, 1912, no. 5; Internationales Centralblatt fur die gesamte Tuberkulose-Forschung, 1912, VII, Jhg., no. 2, p. 67. 144 FACTORS WHICH PREDISPOSE TO TUBERCULOSIS individual who did not also at the same time have pulmonary tuberculosis. On the contrary, not a single instance of pro- gressive tuberculosis has been examined which did not show an ossification of the first costal cartilage. Of the 400 bodies which he examined postmortem with refer- ence to shortening of the first costal cartilage, Hart found in 114 or 28 1 /2 per cent that they were shorter than normal. Of the 114 bodies showing changes in the first rib, 104 or 26 per cent of all suffered from tuberculosis of the pulmonary apices and 78 or 19^2 P er cent of the total number suffered from pro- gressive tuberculosis. He states that this shortening of the rib has a definite effect in producing progressive tuberculosis because 78 or 62.4 per cent of the 125 progressive cases found in the total 400, showed abnormal shortening of the first costal cartilage. How it could do this is difficult to explain. The suggestion of deficient nutrition does not satisfy. This fact is a great deal more suggestive to me of progressive tuberculosis being a cause of the changes in the rib and cartilage, as I shall discuss later. According to the theory which justifies artificial pneumothorax, compression should favor quiescence rather than progressive tu- berculosis. In Hart's 45 cases which were intimately associated with tu- berculosis in the family 34 or 75^2 per cent showed shortening in one or both cartilages, a larger percentage than in non-tuber- culous families. The fact that tuberculosis shows in a larger percentage of those who come from tuberculous families than those who come from non-tuberculous families and that shorten- ing of the cartilage is also more common in these, would indicate that this anomaly seems to be increased with increased danger of infection. The infection also extends to the lungs more often and earlier in children who associate with open tuberculosis in early life because of the greater exposure and more massive in- fection; therefore, the reflex trophic effect produced on the costal cartilages and the effect of lessened motion would be far more apparent, and we would also expect this anomaly to be more common if it were a result of the disease. It is well known that tuberculosis of the lungs is not common in childhood and that if it occurs it usually goes rapidly to a fatal termination; nevertheless, the more massive the infection, REFLEX TROPHIC CHANGES IN FIRST COSTAL RING 145 the greater the danger of pulmonary metastases occurring. This explains the fact that more pulmonary infection is found in the children of families where there has been open tuberculosis than in the families where less danger exists. Mediastinal glands produce a trophic reflex affecting the superficial structures the same as the lungs. With the more massive infection, and the probability of earlier extension to pulmonary tissue and the eon- sequent greater inflammatory reaction, we are led to suspect a more marked trophic reflex in the children of tuberculous fam- ilies than in those free from such association. The greater per- centage of trophic change in the cartilages therefore, is not sur- prising. The most suggestive part of Hart's statistics to me, however, is the comparative relationship between the incidence of infec- tion and the anomalies of the first costal ring. He found that 254 or 63.4 per cent of the 400 bodies examined postmortem showed apical infection, but only 114 or 28V2 per cent showed pathological changes in the costal cartilage ; and that, further, in 78, or 62.4 per cent of the 125 cases of progressive tuber- culosis, shortening of the first rib was found. This would in- dicate that these changes in the costal cartilage are not par- ticularly related to tuberculous infection, but that they are re- lated to active progressive tuberculosis. We know that active progressive tuberculosis, as a rule, is a chronic disease and as such would have greater opportunities to produce trophic changes in the costal cartilage than would abortive infections, such as those which are so commonly found in the apices of the lungs, but which never go on to active development. Likewise, active progressive tuberculosis would favor ankylosis of the costo-sternal articulation by the reduced respiratory excursion which accom- panies active pulmonary disease. These anomalies cannot be discussed except by taking into consideration the mechanics of respiration. Tendeloo 23 in his careful study of the mechanics of respi- ration has shown us that the air cells in different portions of the lungs are expanded unequally. There is only a slight expan- sion of those near the hilus, a little greater in those at the apex, and still a little greater in the para-vertebral area of the su- ^Studie Uber die Ursachen des Lungenkrankheiten, Wiesbaden, 1901. 146 FACTORS WHICH PREDISPOSE TO TUBERCULOSIS perior lobe. These three areas of the lung are particularly those of diminished respiratory movement. The air cells of the lower lobe are subject to greater inspiratory effort and consequently are dilated more. Two forces must be considered in respira- tion. One, the costal rings and the other the diaphragm. The costal rings are so attached to the vertebral column and the sternum that during inspiration not only is the anterior end raised but the lateral portion of the ribs is also elevated (this is especially true of the lower ribs), thus increasing the trans- verse as well as the anteroposterior diameter of the chest. The axes of these costal rings depart from the horizontal in differ- ent degrees. While the first costal ring departs only about 10 degrees from the horizontal, the tenth departs nearly 45 de- grees as shown in Fig. 18. Resulting from this, there is a marked unequal movement of the various portions of the thoracic wall above and below, the movement of the superior being slight while that of the inferior is quite marked. When we add to this the contraction of the diaphragm we have another force which enlarges the thoracic cavity in the vertical direction and which exerts its greatest influence on the lower portion of the lung. The change in position of the diaphragm on inspiration and ex- piration amounts to from one to two inches. Its contraction not only lengthens the thoracic cage but also helps to force out the ribs and increases the transverse as well as the anteropos- terior diameter of the lower portion of the chest. Our knowl- edge of the relative value of diaphragmatic and costal breath- ing in air capacity is not well established. Tigerstedt 24 says relative to diaphragmatic and costal breathing that we have at present but a single measurement of the absolute value of the diaphragmatic as compared with the costal enlargement of the thorax; namely, out of 490 centimeters of inspired air in man about 320 centimeters develop upon the elevation of the ribs and only 170 centimeters on the descent of the diaphragm. While we may roughly say that the expansion of any par- ticular portion of the pulmonary tissue depends upon the mo- tion of the thoracic wall immediately over it, as suggested by the law of Tendeloo, quoted by Hart, yet this is not wholly true, 2J Text Book of Physiology, D. Appleton & Co., New York, 1906. LOCALIZATION OF BACILLI AND RESPIRATORY MOVEMENT 147 because the action of the diaphragm exerts its influence even to the apex of the lung as shown by Keith. Keith 25 says that these physiological facts (referring to the motion of the pulmonary tissue and the distention of the air cells in the various parts of the lung) have a very important bearing upon the localization of the tubercle bacilli and the pre- disposition of the lung to infection. Tubercle bacilli find most favorable conditions for implantation in these areas of lessened lung expansion. This fact has been used to support the theory of Freund, but it seems to me that there are many points which show that the cause of the tendency for tubercle bacilli to be implanted in the apex or the posterior aspect of the superior lobe is more fundamental than shortening of the first costal carti- lage and its compressing influence upon the pulmonary tissue. If it were due to the compression from the rib we would expect to find the implantation occur not posteriorly where it so often does, but laterally where compression is greatest. In reality the movement of the first pair of ribs and the manu- brium, as Keith shows, expands particularly the anterior or ventrolateral part of the apex of the lungs, particularly that part of the lung in front of the neck of the first and second pair of ribs, where implantation so commonly occurs; so it seems to me that since there are other ways of satisfactorily account- ing for the ankylosis of the first costo-sternal articulation arid shortening of the first rib and costal cartilage, and since the im- plantation of bacilli does not occur where we would expect it to occur from the nature of the case, if it were due to the ac- tion of this first costal ring we are forced to look for some other cause which operates to favor apical infection. That this short- ened rib, where it does occur, is a factor in compression, cannot be denied; but it seems to me more probable that it is only a part of a greater cause and not the cause itself. This greater cause, I believe, is found in the changes which take place in respiration as the child grows in years and adolescence is ap- proached. Habitus Phthisicns. — This subject has received attention from many writers, particularly Schliiter. 26 There has been described a 25 Further Advances in Physiology, Hill, London, 1909. 2C Die Anlage zur tuberkulose, Wien, 1905. 148 FACTORS WHICH PREDISPOSE TO TUBERCULOSIS certain form of body which has been thought to have a predis- posing influence to tuberculosis; but, now that we understand the tuberculous infection and its effect upon the human body better, we know that in many instances habitus pTithisicus is not a predisposing factor to tuberculosis but a result of tubercu- losis. We further know that while this peculiar build furnishes its just proportion of victims to tuberculosis, yet there is no form or shape of body that is not susceptible to tuberculous in- fection. Moeller 27 says that any practitioner knows that at least three-fourths of his tuberculous patients have a normally built thorax. My own experience would confirm this view. The principal characteristics of habitus pMhisicus are a long flat- tened chest with wide intercostal spaces, prominent clavicles, long thin neck, acute costo-sternal angle, winged scapulas, with a tendency to scoliosis. The individual is usually tall and has weak musculature. To this has been added more recently the anomalies of the upper aperture of the thorax (Freund) as well as that of a floating tenth rib. 28 The Small Heart. — It is necessary in dealing with the special factors which predispose to tuberculosis to give attention to the fact that for many years the size of the heart has been consid- ered as a causative factor. While I have discussed the cause of this more fully elsewhere in these pages, it is necessary to men- tion it here in connection with the subject under discussion, but I would refer those interested to the fuller discussion on page 301. Brehmer was convinced at the autopsy table that the small heart was present in a large number of tuberculous subjects and was convinced that it was a predisposing factor in the produc- tion of the disease. He reasoned that, the heart being small, the lungs were proportionately large for the amount of blood they received, consequently, on account of undernutrition,, be- came diseased. It must be remembered in reading Brehmer 's work that his ideas were given out in the prebacillary days. His belief in the existence of the small heart in tuberculosis was based on 12,000 careful personal observations. It was found that the small heart existed not only in the 27 Lehrbuch der Lungentuberkulose, Wiesbaden, 1910. 28 Stiller: Die asthenische Konstitutionskrankheit, Stuttgart, 1907. SMALL HEART AND TUBERCULOSIS 149 bodies of those who came to autopsy, as a result of their tuber- culosis, but in those who died of accidental death and in whom an early or moderately advanced infection Was found. In such cases the small heart was attributed to some defect of develop- ment and was naturally considered as having a causative rela- tionship to the disease. My suggestion for the cause of the small heart is a physiolog- ical one. 29 It is based upon the fact that aside from the strength of the heart muscle and the elasticity of the vessel walls, the greatest accessory factor in the circulation of the blood is the suc- tion action caused by the inspiratory act, which accompanies the enlargement of the thoracic cage. With every inspiration the negative pressure in the thorax is increased, the vessels are opened and the blood is drawn from the systemic veins and delivered to the heart. Any condition which interferes with in- spiration reduces this suction action and consequently causes less blood to be delivered to the heart. The heart, receiving less blood, contains less blood and delivers less blood at each sys- tole. The result is that it accommodates itself to the condition and becomes smaller. The same cause operating, causes the relatively small arteries which likewise have been described as being predisposing to tuberculosis. 29 The Small Heart in Tuberculosis: A Physiological Explanation, Journal American Medical Association, April 17, 1915. CHAPTER VI. THE NERVOUS SYSTEM IN TUBERCULOSIS. Psychoses. — The nervous system shows very interesting and important changes in tuberculosis. These departures from the normal affect the .nervous system at all levels, physico-chemical, sensorimotor, and psychical. The relationship between tuber- culosis and insanity has long been recognized. The death rate from tuberculosis among the insane of asylums is double or quadruple that of the general population. This is not so diffi- cult to explain now that we know the frequency of infection in the human race and also know that the advanced lesions of later years may be due to renewed activity in old foci. The lowered resistance of the insane can readily bring about condi- tions favorable to the multiplication of bacilli ; and when activity has once started, the patient offers feeble resistance to the spread of infection. In some instances, on the other hand, the tuberculous process with its toxins is most likely the active force in the production of insanity. I have seen several cases of insanity which were complications of active pulmonary tuberculosis in which the tuberculosis seemed definitely to be the etiological factor. Jessen is of the opinion that diseases dependent on degenera- tion of the nervous system are more common in tuberculous fam- ilies than in the non-tuberculous. A very interesting psychical disturbance which has come un- der my observation on several different occasions is that of double personality. I have seen a number of patients who, a short time prior to death, became extremely confused and thought themselves two different individuals. In one instance the pa- tient kept expectorating carelessly about on the bed clothing and floor, and, when reproved for it, said that he was two indi- viduals and that the other fellow did the expectorating and used the cup. Such patients sometimes think that one personality is a long way off and the other one present. I have noticed this as a terminal symptom, coming on during the last few weeks PSYCHONEUROSES 151 of life, except in one instance under my care at the present time. This patient, a young woman, began to suffer from active symp- toms accompanied by fever about four months ago. One month later she was having chills with high fever, and suffered greatly from the cold. In describing her conceptions, she says that she herself was always comfortable, but that she could not keep the other personality warm no matter how much cover she used. She also thought of the other person as doing all of the coughing and expectorating, while she did none. This patient is suffering from advanced caseous tuberculosis with fever and a complicating tu- berculous enteritis. (She died two months after this was writ- ten, six months after first noting the double personality.) Psychoneuroses. — More frequent than the psychoses are the psychoneuroses and neuroses. Tuberculosis often develops in in- dividuals of the nervous type. Sometimes this nervous condi- tion is inherited. In those of the enteroptotic type (astJienica universalis congenita), Stiller claims that the nervous character- istics are present from birth but become manifest more particu- larly after puberty. In other instances the nervous symptoms gradually appear as a result of toxins which develop in the focus of infection. In many children tubercle toxins injure the nervous system, destroying the nerve balance ; and, through this, interfere with proper physical development. This harmful influence on the nervous system is often carried on for a prolonged period be- fore frank clinical tuberculosis develops. It is often difficult, under such circumstances, to tell whether the nervous condition or the tuberculosis existed first. The nervous side of tuberculosis has impressed some authors so thoroughly that they look upon it as being a nervous dis- ease. One can readily understand how the toxemia of tubercu- losis can produce a vicious circle by its action upon the nervous system and, through it, interfere with the physical development. Realising that one of the important functions of the nervous system is to preside over the nutrition of the body cells, the effect of a more or less constant toxemia, such as that produced by chronic tuberculosis, is evident. By its action on the neurons there is a constant disturbance in nerve impulses which must be conducted to the tissue cells through the nerve filaments. It is 152 NERVOUS SYSTEM IN TUBERCULOSIS quite possible that this is the true cause of the degenerations which result from toxemia. "While, as yet, we are not wholly able to explain the action of toxemia, yet we are able to say that its force seems to be spent directly upon the central nerve cells, the effect of which is shown in disturbed function. "While our knowledge of the physiology of the nervous system would not permit us to believe that the sympathetic neurons alone are involved, yet the syndrome of toxemia is that of a general discharge through the sympathetic nervous system. "We must conceive that the chronic toxemia produces more or less constant stimulation of the nerve cells of the central nervous system. Eesulting from this they become more or less irritable, fatigued and later, exhausted. This ir- ritability is shown in dysfunction on the part of the organ re- ceiving its nerve impulse from the cells which are involved. One particular action caused by toxins is its stimulation through the sympathetics of the adrenal gland with an increased produc- tion of adrenin. This, again, stimulates the sympathetic nerves peripherally and prolongs the action produced by toxemia. "While the toxins act upon the central nerve cells, adrenin acts peripher- ally at the myo-neural junction. "With stimulation of the sym- pathetics, either centrally or peripherally, we have a general in- hibition of function throughout the important internal viscera which produces an extremely deleterious effect upon the organ- ism as a whole. The irritability of the nerve cells shows itself by a lowering of the threshhold of response, so that a stimulation which, under ordinary circumstances, would be withstood by the nerve cell without resultant action, calls forth an action more or less in- tense. From this description it can be readily seen that the psycho- neuroses of the. tuberculous are characterized by lack of endur- ance and increased irritability. Nearly every adult who suffers from clinical tuberculosis has a more or less pronounced neurasthenia, which becomes more marked as toxemia is prolonged. These patients suffer from malaise. They are weary even without exertion and tire unduly upon the least effort, whether of a physical or mental nature. Added to this is often a complete change in nature, an irritabil- MENTAL ATTITUDE 153 ity, a lack of self-control. A quiet nature may become easily angered and even quarrelsome. Dependence is also a common symptom. Patients who have been self-reliant often lose their confidence in themselves. They like to have things done for them, and even see their friends make unusual sacrifices with- out show of appreciation. The nature of the tuberculous often becomes much like that of the child, — selfish, self-centered, irritable, easily angered and easily pleased. McCarthy and Carncross 1 present a careful study of the mental attitude of the tuberculous patients treated under their care during the years 1904-5. The mental attitude of these pa- tients might be somewhat different from that of the patients in the well-to-do class, but the analysis is very interesting. Carn- cross says: "The question, then, must be not are tuberculous people par- ticularly optimistic or hopeful or cheerful or anything else, but do they undergo a change of mental state? And this I think may be answered reservedly in the affirmative — so reservedly, indeed, that one must say that generally the change is due to chronic illness rather than to tuberculosis specifically. Having claimed this freedom from specific influence, one must promptly whirl about and assert that in a certain number of cases the dis- ease does not affect the brain markedly, — that here are found more or less characteristic mental states which are over the borderland. But of these I shall speak later on. "Well, then, in the long run, what are the changes, if there are any, in disposition or mental state that the tuberculous in- dividual does undergo 1 ? They are what one would expect from the condition of the general nervous system, which is one of irritability — the irritability of weakness. The spinal reflexes are almost universally increased before the very advanced stages have been reached, in a limited number of which, as Doctor Mc- Carthy has shown, they are abolished. And this same irritability is evident in the brain. The vast majority of tuberculous pa- tients will promptly admit that they are irritable since they have been afflicted with the disease. They frequently describe them- 1 Second Annual Report of the Henry Phipps Institute for the Study, Treatment, and Prevention of Tuberculosis, Philadelphia, 1906. 154 NERVOUS SYSTEM IN TUBERCULOSIS selves as 'cranky.' "With this, in many eases, is a greater ten- dency to worry, though here, of course, circumstances, which have become so much more unfavorable, play a large part. But the sense of apprehension and the dread of trouble, as well as the susceptibility to annoyance, are increased independently of external conditions. The patient often admits that he is less cheerful and less sociable, and that his outlook tends more to- ward pessimism. On the other hand, he may simply be more indifferent, or quieter, or have become entirely ambitionless. Any one, two, or all of these changes may be present in the tuberculous individual." The following tables which are self-explanatory, show the nat- ural disposition of the patient and the attitude after tuberculosis has developed (McCarthy and Carncross). They do not bear out the universality of the condition of spes plitliisica which seems to be so generally accepted. Disposition. Patients with Cheerful temperament. 155' Unhappy temperament. 22 Intermediate tempera- ment 29 No record of tempera- ment 31 Some change in dispo- sition 148 (18 non-tuberculous) No change in disposi- tion 58 (5 non-tuberculous) No record of change in disposition 31 (7 non-tuberculous) 237 Present Mental Attitude. {Hopeless regarding disease 166 Not hopeful regarding disease . . 32 Indifferent regarding disease. ... 1 No record 38 Patients who were rMost of the time. 62 Depressed. . . J At times 49 [Seldom 14 Not depressed 71 No record 41 Patients f Suspicious 10 who were \ Not suspicious 184 I No record 43 16 non-tuberculous) 1 4 non- tuberculous) I 007 10 non-tuberculous) J 6 non-tuberculous) 10 non-tuberculous) 1 non-tuberculous) 6 non-tuberculous) 7 non-tuberculous) } 237 2 non-tuberculous) "1 20 non-tuberculous) > 8 non-tuberculous) J 237 Five of the one hundred and eighty-four recorded as not suspicious were ques- tionable. TUBERCULOSIS AND MENTAL ATTITUDE 155 The tuberculous patient is generally looked upon as being one of unusual hope. I have never been able to make up my mind that he is far different in this respect from what he was before his illness. One optimistic when well, is apt to be when ill of tuberculosis, and there is surely nothing in this disease that can turn a pessimist into an optimist. If we consider the seriousness of the disease we must marvel at the hopefulness of those who are inclined to be of a hopeful nature; on the other hand the confirmed pessimist is, at least, as hard to cheer and encourage when tuberculous as when well. There is one factor which acts by inspiring hope all along through the course of the disease. That is that they have spells of illness, the disease becoming more active than usual and be- ing accompanied by temperature, chills, and other symptoms of toxemia, increased cough and expectoration, to be followed again by a remission or cessation after a short time. They see this so often that they expect it, and consequently learn to look for- ward to the time when they will be better, no matter how ill they are. While this is the attitude of the optimist, the pessimist often greets his physician, who is trying to encourage him, by such statements as: "Yes, but how long will it last?" or "Yes, but I have been this way before and it always gets worse. ' ' Com- pared with the patient with severe acute illnesses, in which tox- emia is a factor, or chronic diseases accompanied by toxemia, I think the tuberculous patient is in about the same frame of mind during his periods of acute activity, and during lesser ac- tivity, as one with other chronic toxemia ; but, of course he is hope- ful and buoyant, if an optimist, when the toxic symptoms have passed off. If a pessimist he is always pessimistic. I have never been able to determine that the tuberculous patient, with severe gastrointestinal complications is any less depressed than the non- tuberculous with the same symptoms. The tuberculous patient is often described as one who is par- ticularly credulous and easily duped. In this way do some ac- count for the fact that he is preyed upon to such an extent by quacks, charlatans, and the unscrupulous. Is he more easily duped than the average human being? Before answering this we must recognize that he is suffering from a serious fatal dis- ease. Our profession has offered him little hope, in fact, has told him time after time, that it can do nothing for him. Nat- 156 NERVOUS SYSTEM IN TUBERCULOSIS urally, he exercises his right, if not his judgment, and turns to the thing that does offer hope. It is doubtful whether this is an indication of excessive gullibility. Is it not just as apt to be a bowing to the principle of self-preservation, the first law of nature? Are they more gullible than others who follow fake advertisements not only in medicine but in every-day transac- tions? Are they more easily duped than other intelligent people who blindly follow cults and fakers'? The fact has been cited that they are so easily preyed upon that any new measure for relief is accepted with unusual eager- ness and that every suggestion of itself is apt to be noted. This may be explained on the ground that relieving fear and discour- agement and substituting hope in their place relieves the patient of sympathetic inhibition and improves his general tone, as noted on page 224. This is not peculiar to the tuberculous. The non- tuberculous can also be put to sleep at times by a hypodermic of sterile water; so can they be relieved of pain by the same. The human race, as a whole, is influenced by suggestion, and to this the tuberculous patient is not an exception. One of the greatest factors in handling the tuberculous patient is sugges- tion. This factor is most important in its influence on the ner- vous system. The nervous system controls every function of the body, so its effect is far reaching. Positive suggestion is a powerful force and should always be employed. It should be so positive too that it will overcome all negative suggestions that can come from outside sources. It is difficult to measure the influence of suggestion upon the cure of tuberculosis, but it can- not be denied that proper suggestion will relieve sympathetic inhibition, produce a calm state of mind, induce sleep, improve digestion and assimilation, and have a favorable influence upon the heart and circulatory system ; but, this it will do for the non- tuberculous as well as tuberculous. There are many circumstances, when numbers of tuberculous patients are under close observation, that make it appear that they lack will power and are extremely easily led. In my ex- perience I would say that three-fourths of the patients who have confidence enough to seek my aid are willing to cooperate to the best of their ability, while the others need considerable at- tention to hold them to conscientious work. In discussing this TUBERCULOSIS AND MENTAL ATTITUDE 157 in a former paper 2 the writer said: "The patients who enter an institution belong to three classes. The first comprises the great majority of patients and consists of those who want to do what is right, who are conscientious and earnest in their desire to get well. To be sure these, at times, fall from grace; but, most of the time they are working conscientiously for recovery. Then, there is a small class, probably about twenty per cent, who have no well defined principles, but who are willing to be conscientious if they fall in with the conscientious class, and who are just as willing to be insincere if they are led that way. Then there is still a small number, less than five per cent, who are vicious, willful and unfaithful to themselves and all with whom they come in contact. This class, however, can often be controlled by patience and firmness." I am not sure that a lack of cooperation on the part of the few can be attributed to lack of will power. It is rather thought- lessness combined with the usual disregard of other people's rights and an unwillingness on their part to submit to authority. It may be exaggerated over what it would be among an equal number of well people, yet of this, I am not sure. Von Muralt 3 speaks of the suspiciousness of the tuberculous patients and notes how they mistrust particularly those who are trying to do for them. He also speaks of their egoistical na- ture, their lack of regard for others. He speaks of how at times they will suddenly become dissatisfied with everything that is being done for them; and says that every sanatorium physician has met epidemics of complaints against the administration and dissatisfaction with the methods of treatment which were not only unfounded but amounted to base ingratitude. Such attacks as these are accounted for on the ground of toxic disturbances of the nervous system. There is no doubt of the effect of the toxins upon the nervous system, yet such behavior has nothing to do with tuberculosis itself. True, it may be somewhat ac- centuated by it; but would not these same tendencies show them- selves in any group of individuals who were under similar dis- 2 Some of the Problems of Private Sanatoria for Tuberculosis as Observed During Ten Years' Experience in the Pottenger Sanatorium for Diseases of the Lungs and Throat, Boston Medical and Surgical Journal, vol. clxxi, no. 4, pp. 142-147, July 23, 1914. 8 Die nervosen und psychischen Stoerungen der Lungentuberkulosen, Medizinische Klinik, 1913, N. 44 and 46. . i ■ 158 NERVOUS SYSTEM IN TUBERCULOSIS appointment and discouragement, and under the same restraint; and would not they manifest themselves in any group of indi- viduals suffering from chronic toxemia from any other cause? Insomnia is often a symptom which seems to be exaggerated in tuberculosis. This is very apt to occur in people who are of a nervous temperament. An obstinate insomnia which fails to yield to ordinary and even extraordinary doses of hypnotics, is a very common symptom which comes on a few weeks before and persists until death. Hezel 4 quotes the following statistics of marked instances of psychoneuroses in tuberculosis. He himself found it in 30 to 40 per cent, Phillipi in 66.1 per cent of all patients of which there were 52 per cent in the first stage; 59 per cent in the second, and 76.6 in the third stage. The ultimate dependence of these neurotic symptoms upon toxemia may be inferred, however, from the fact that they are often markedly increased during acute activity and disappear with its quiescence. During the time that necrosis and cavity formation are occurring we, at times, find these symptoms very pronounced and see them let up simultaneously with the rupture and expulsion of the contents. These symptoms, although very pronounced when the patient is living under unhygienic condi- tions, are, at times, relieved at once when the patient is put at rest under a hygienic regime. The fact, however, that many of them can be markedly relieved by suggestion, indicates that toxemia is not the only factor. The effect of depressive emo- tional states such as pain, discouragement, fear and disappoint- ment must be taken into consideration in this connection. For a more complete discussion of this interesting phase of the sub- ject see Chapter VIII. There seems to be considerable habit in all cases of psychoneuroses; although, to begin with, there is some physical foundation in practically all instances. The relationship between neurasthenia and tuberculosis is gradually becoming better recognized. The toxins of tubercu- losis are especially prone to affect the nervous system. Now that we begin to appreciate the fact that tubercle bacilli taken into the body during childhood may not produce active tuberculosis 4 Tuberkulose und Nerven System, Handbuch der Tuberkulose, Brauer, Schroder und Blumenfeld, Bd. iv, 1914. TUBERCULOSIS AND NEURASTHENIA 159 until later in life, we begin to understand how these infections may be able intermittently to give off enough toxins to impair seriously the nervous system, without producing more active symptoms. Every observing clinician can probably recall cases of so-called neurasthenia which have, upon careful analysis, proved to have a partially quiescent tuberculosis as their causa- tive factor. This can be understood by realizing that the toxins constantly bombard the cells of the central nervous system and irritate them to the point of exhaustion. It is extremely important to bear this in mind, particularly in young girls and boys during the age of adolescence. In nor- mal individuals this should be the period of exceptional devel- opment and increased strength and power. We find quite a proportion of young people, who, instead of taking upon them- selves this extra growth, seem to be unable to measure up, and seem to gradually lose in strength and power instead. This is the time those suffering from astJienica universalis congenita (Stiller) begin to show this stigma most. It is the time when the so-called neurasthenic condition begins. While there are un- doubtedly many individuals whose lack of nervous and physical force is a congenital factor, yet there are many others who de- velop this after birth, showing it particularly after the age of puberty. I wish to emphasize that the tubercle toxins which are given off from the semi-quiescent foci which are often present in early life and adolescence are responsible for many cases of neuras- thenia. This is true to such an extent that tuberculosis should always be considered as one of the etiological factors in neu- rasthenia coming on at this time of life. I have seen many young people, particularly girls, who were gradually lapsing into this neurasthenic state, who have been relieved and practically made over by discovering that the tuber- culous toxemia was the underlying cause and relieving it by proper treatment. Pathology of Psychoses and Psychoneuroses. — Dupre, 5 quoted by Hezel, speaks of the pathology of the psychoneuroses and psychoses in tuberculosis. He mentions a patient who came to postmortem who, during the last few months of life, had suf> B Euphorie d&irante des phthisiques, Etude anatomaclinique Revue neurol, 1904, No. 16, Ref. Neurologisches, Centralblatt, 1904, p. 1164. 160 NERVOUS SYSTEM IN TUBERCULOSIS fered from light characteristic attacks of depressive mania. He found over the frontal lobe slight thickness of the meninges with- out adhesions, also a slight hydrocephalus, but no signs of tu- berculous infection. Histological examination using Nissl stain showed a simple meningitis, not inflammatory in character; and without diapedesis. In the brain there was a slight proliferation of the epithelium of the vessels, pigmentation around the vessels, and, in the tissues surrounding the capillaries, an occasional columnar cell. Scarcely any increase of the glia cells was ob- servable. In the ganglion cells of the frontal lobe there were marked degenerative changes, also destruction of the white sub- stance. Chains of strepto-bacilli were seen around some of the vessels. In the other portions of the cortex these processes were much less marked. Dupre considers them as purely toxic, neither of a meningeal nor bacillary nature. Levastine, 6 quoted by Hezel, reports that he has found cell degeneration in the cortex of tuberculous patients who had shown evident psychoneurotic disturbances during life; and has noted marked pigmentation of the cortical cells in cachectic pa- tients. These reports are very interesting because they show the extent of the toxic influence of this disease. Tuberculosis and the Peripheral Nerves. — The influence of tu- berculosis upon the peripheral nerves has received some study during recent years, although for the most part it has been neglected. A nerve may either be influenced directly by the tuberculous process in adjacent tissue such as occurs when the vagus nerve is bound down by enlarged mediastinal glands, or the phrenics are involved in apical adhesions or the intercostals are involved in instances of pleural adhesions; or, as pointed out by Gustav Liebermeister 7 the nerves themselves may be in- fluenced through the direct action of bacilli. The toxic influence has been previously mentioned and is undoubtedly of consider- able importance. Reflex action upon the peripheral nerves has particularly interested the writer for a number of years. The disturbance in the larynx in early tuberculosis is sometimes 6 Reclierches histologiques sur l'ecorce cerebrale des tuberculeux Revue de Med., No. 3, 1907, Ref. Jahresbericht d. Neurol, u. Psychiatr. 'Studien iiber Komplikationen der Ivungentuberkulose und iiber die Verbreitung der Tuberkelbacillen in den Organen und im Blut der Phthisiken, Virchow's Archiv fur pathologische Anatomie und Physiologic und fur Klinische Medicin, vol. xix (series 19, vol. vii), part 1-2-3. EFFECT ON PERIPHERAL NERVES 161 thought to be due to the recurrent laryngeal being compressed by enlarged mediastinal glands. I think, however, that this is more apt to be a reflex hoarseness which appears in tuberculosis and presents two different pictures upon physical examination. In one instance there is an inability to adduct. This is due to interference with the action of the recurrent laryngeal. In other instances the cords approximate at the ends but lack tone and consequently do not approximate in the middle. This is due possibly to interference with the action of the superior laryn- geal. I am inclined to think that these processes are due to a reflex stimulation from the disease in the lung, the irritation starting in the inflammation in the lung, the afferent impulse traveling to the brain and coming back through the superior and inferior laryngeal nerves. I have gone into the question of re- flexes more fully elsewhere and would refer my reader to page 385. In 1912 the writer reported several cases of acute neuritis re- gional in character which resulted from tuberculosis. 8 Two of these involved the brachial plexus. Since that time I have had seven others under my care, making nine cases of brachial neu- ritis in all, which were confined to the side of severest involvement and greatest activity in patients suffering from pulmonary tuber- culosis. The fact that they were confined to the side of the in- volvement; or, where both sides were involved, to the side of greatest activity, warrants the belief that they were directly re- lated to the disease. In my papers dealing with muscle spasm as a motor reflex 9 I called attention to the fact that these nerve lesions are not a part of the general nerve disturbance which might be due to toxemia, but have a definite regional character. The fact that this regional relationship can be traced anatomic- ally to an association between the cervical nerves and the sym- pathetic nerves which supply the lung leads us to the con- clusion that they are reflex in nature. Patients having tubercu- losis suffer from sensory, motor, trophic and secretory disturb- ances of reflex character and in some of these instances the 8 Chest and Shoulder Pains in Pulmonary Tuberculosis, Transactions of the American Climatological Association, 1912. 8 Muskelspasmus und Degeneration, ihre Bedeutung fur die Diagnose intrathorazischer Entziindung und als Kausalfaktor bei der Produktion von Veranderungen des knoch- ernen Thorax und leichte Tastpalpation, Brauer's Beitrage zur Tuberkulose, Bd. xxii, part 1, 1912; Muscle Spasm and Degeneration in Intrathoracic Inflammation and Eight Touch Palpation, C. V. Mosby Co., St. Louis, 1912. 162 NERVOUS SYSTEM IN TUBERCULOSIS nerves themselves show a distinct pathology. Clinically, where the nerve is inflamed, it is accompanied by certain phenomena. Pain is a common accompaniment, although it may be so slight in character that it is only an uneasiness or a feeling of being tired. These sensations are expressly noticed through the shoul- ders and interscapular region and are nearly always confined to the side where the lung is involved. A pain of this character which I have not previously seen described is one which affects the pharynx. This, when present, nearly always comes on when the disease is far advanced. The patient complains of pain in the throat and yet nothing can be seen. These pains are entirely different from the sensory disturbances which have been de- scribed by Head. Head has shown segmental relationship be- tween the reflexes of the lung and the skin, and in this has laid the foundation for the theory underlying the writer's observa- tions. Every internal organ has a corresponding area on the surface of the body in which hyperalgesia may be reflexly de- veloped when the organ is inflamed. This area is the one sup- plied by sensory nerves from the segments of the cord which are in communication with the affected organ through the sympathetics which supply it. The segments of the cord which stand in particu- lar relationship to the lungs are the third and fourth cervical and third to ninth dorsal, particularly the fourth and fifth dorsal. The lungs are connected by few communicating branches with the fifth to eighth cervical nerves. Not only do we have sensory, but also motor reflexes as I have shown. The motor nerves in reflex communication with the lung show true degenerative inflammation. In this way I account for the instances of neuritis which I mention. Justi- fication of the theory that these pains are due to inflammation of the nerve from reflex sources, is found in the clinical fact that the muscles supplied by the nerves from the segments in question take upon themselves increased tone or spasm when the pulmonary involvement is active, and degeneration when it quiets down, which indicates a serious nerve disturbance. In a former discussion the writer said: 10 "While I do not wish to enter into a full discussion of the 10 Muscle Spasm and Degeneration in Intrathoracic Inflammation and Eight Touch Pal- pation, C. V. Mosby Company, St. Eouis, 1912. TUBERCULOSIS AND PERIPHERAL NEURITIS 163 many pains that accompany intrathoracic inflammations (espe- cially when found in tuberculosis) yet I cannot refrain from suggesting that their character indicates that some of them are phenomena of reflex origin. I am well aware that the theory of a reflex will not explain all, for we must recognize pleurisy, pressure pains, and general pains which are found in all parts of the body which may be of toxic origin. But, aside from these, we have regional or localized pains, the same as we have local- ized muscular contractions and atrophies, which must be ex- plained by some locally acting cause. As a hint to explanation we find these localized pains for the most part, as far as I have been able to determine, on the same side on which the involve- ment exists. Thus it seems natural to suggest for them a com- mon cause with other reflex phenomena. "Of such regional pains the vague sensations which are found in the shoulder or shoulders in case of infection of both lungs must be mentioned. These often begin as early as clinical symp- toms appear. They vary in intensity from a mere 'feeling of being tired' to an aching more or less severe. Aside from these vague feelings of discomfort we find pains of a very severe char- acter which leave no doubt as to their nature. They are a true neuritis. These we find especially about the neck, shoulder (oc- casionally running into the arm), and upper portion of the chest both anteriorly and posteriorly. I have seen some instances in which the pain in these cases was so severe that it was neces- sary to resort to morphine injections. In some cases which I have observed there was a marked wasting with loss of muscular power. One thing characteristic of all these pains is that they are not constant. They come and go and are influenced by weather conditions and barometric changes. "These cases have been misunderstood, wrongly diagnosed and consequently wrongly treated. They are quite often treated for rheumatism. "The following cases will illustrate the severe forms: "Mrs. B. Age 32, had suffered from a slight infection of the right apex and an advanced tuberculous process of the upper left lung which had ended in cavity formation and healing. She had also had tuberculous ul- ceration in the interarytenoid space and left cord which resulted in heal- ing. She suffered a great deal from aching of the left shoulder during her illness, and during the latter part of her treatment suffered severe 164 NERVOUS SYSTEM IN TUBERCULOSIS pain running up the left side of the neck, which persisted, at intervals, for months, and then finally disappeared. "Mr. L. consulted me in February, 1911, for a widespread ulcerative condition of the larynx. Upon examination of the chest I found an old fibroid lesion of the right lung occupying the upper half of the upper lobe, which was the seat of renewed activity. I told him my findings, that he had evidence of an old lesion in the lung. He protested that it could not be. I inquired as to his reason for leaving Philadelphia, which was his former home. He said he left because he had suffered from a severe rheumatism of the right shoulder which partially incapacitated him for business. I asked him if he was examined. He said he had consulted nearly a dozen of the best men there, all of whom had pronounced the ease rheumatism. None had given him an idea that tuberculosis was pres- ent. During his last illness, for it proved fatal, he again suffered to some extent from the same pains. I have no doubt that his pains were due to a neuritis of reflex origin, the cause being the tuberculous process in the lung. "Mr. G. consulted me in January, 1912, suffering from a pain in the upper part of the right chest which at first was considered to be of pleural origin. Owing to my inability to understand the patient's language, he being a foreigner, I was somewhat deceived for a few days. I found upon examination that the major portion of the upper lobe on the right side was involved in an old chronic tuberculous process and at the apex there were signs of cavity formation. His clinical history was interesting. He had always enjoyed good health, and, being a man of means, had lived well. In September, 1911, he was taken suddenly ill with chill followed by fever, severe cough, free expectoration and hemorrhages. The patient made a good recovery and had no further trouble until December, 1911, when the same thing occurred again. This was followed in about two weeks by the pain which I mentioned. The patient was admitted to the sanatorium and carefully watched; the pain persisted, coming on in severe paroxysms two or three times a day, sometimes requiring morphine. It lasted from a few minutes to one or two hours at a time. It is now nearly six months since it started and it seems to be gradually becoming less severe and less frequent. The pains seem to be confined to the brachial plexus, and particularly certain branches of it; viz., the dorsalis scapula? supplying the rhomboidei, the thoracales anteriores supplying the pectoralis minor and major, the axillaris supplying the deltoideus and shoulder joint. Many of the other branches are also involved but these show the greatest pain. The muscles covering the anterior and posterior surface of the upper part of the chest, the shoulder and arm are all markedly degenerated and the strength of the right arm is very much reduced. "It is very necessary to recognize these pains, for they offer suggestive diagnostic hints. Any of these pains, especially, if they are confined to one shoulder or the upper portion of the chest, call for careful examination of the lungs, to exclude a pulmonary involvement before any other diagnosis is made." BRACIAL NEURITIS AND TUBERCULOSIS 165 I wish to append the two following cases to further emphasize and illustrate the effect of tuberculous involvement of the lung in the production of brachial neuritis, Case 2422. Merchant, aged 35. Entered the Pottenger Sanatorium for Diseases of the Lungs and Throat, April 24, 1914. Family History. — Mother died at 68, cause unknown. Father, living and well. One brother died of tuberculosis at the age of 21; two sisters died of tuberculosis at the respective ages of 23 and 30 years, all dying within a period of three months at the time the patient was ten years old. One was ill eight years, one three years, and one a year and a half. Personal History. — The patient was never strong and was much under weight. He had the ordinary diseases of childhood with prompt convales- cence. For many years had suffered periodically from severe hyperacidity and dilatation of the stomach, but no definite localized pain. Had vomited occasionally, the vomitus was never bloody. Five years previous the patient had suffered an attack of pleurisy on the left side and on two or three occasions had raised small quantities of blood, the amount varying from a dram to a half ounce. The patient was examined at that time by a general practitioner and told that he had an old spot in the left lung. The patient gave this slight consideration. Several times during the past five years this patient has suffered from hoarseness, which would last for several weeks at a time. The present illness began about a year and a half prior to the time of consulting me, at which time the patient developed a persistent cough with some expectoration. A few months later his strength declined. ' He felt tired; his appetite began to fail; he also lost weight. Four months previously his throat became painful on swallowing, and was especially irritated by acids. Two weeks previously he suffered from attacks of pleurisy on the right side. At times he raised a small amount of blood. For four months past his voice had been decidedly husky most of the time. Had suffered from constipation for many years, apparently of the spastic type. Immediately prior to his entering the sanatorium he suf- fered from a very severe diarrhea of several days' duration. He weighed 124% pounds, his normal being 145 pounds. He slept fairly well and had no shortness of breath or night sweats. Examination at the Time of Entrance.— His temperature was 99.4°, pulse 86, B. P. on the right side 115- on the left 95. Complexion, sallow; poorly nourished. Physical examination of the chest showed severe infiltration of the up- per two-thirds of the left lung, with a large cavity and diffuse infiltration throughout the entire left lung. The right side showed moderate infiltration of the upper and middle lobes and of the apex of the lower lobe. The larynx showed marked infiltration of the arytenoids and inter- arytenoid space and slight ulceration. Brachial Neuritis. — Immediately prior to entering the institution the pa- tient had some pain in the left shoulder which became very severe after he had been in the institution for a few days. The pain was constant, 166 NERVOUS SYSTEM IN TUBERCULOSIS and affected the entire arm, but was most severe about the shoulder and upper arm. This pain was also accompanied by marked loss of strength which involved the entire arm.. The pain was so severe that it was im- possible for him to rest in any position and he was unable to sleep at night. The diagnosis of brachial neuritis was made. It is interesting to know that this involved the same side as the severe involvement in the lung. After a month the pain gradually began to lessen and in six weeks' time it disappeared. Case 2375. Farmer, aged 51. Admitted to the Pottenger Sanatorium on November 18, 1913. Family History. — Two brothers died of tuberculosis at the age of 21 and 23 years, respectively, at the time patient was about thirty years of age. Patient lived with brothers during their illness, but this was not the prob- able source of infection because, as will be seen, the patient had had pleurisy thirteen years before. Tuberculous History. — At the age of eighteen the patient had a left- sided pleurisy. At the age of thirty-six developed cough with some ex- pectoration and about the same time had a hemorrhage. Changed resi- dence, going to some springs, where he improved markedly and from that time on had good health until 1908, when he contracted what seemed to be a cold; but it was accompanied by fever and a gradually increasing cough, and was followed by considerable loss in weight and strength. From that attack he never fully recovered and was unable to work up to the time he consulted me. He spent eighteen months in a sanatorium in Iowa in 1912 and 1913. During his stay there he improved and at the time he was admitted to the Pottenger Sanatorium, he tired easily, had a capricious appetite, good digestion, a great deal of irritation in the larynx, followed by cough, some hoarseness, also some pain in the left shoulder. Tem- perature 99°, pulse 78, B. P. 110, weight 202 pounds, which was about a normal weight for a man of his size. Physical Examination. — Physical examination revealed widespread disease in both lungs. In the upper portion of the left there was a suppurating cavity. The disease was not very active, but more of the fibroid type. In the right lung there was considerable activity, but without much breaking down. On discharge from the sanatorium July 21, 1914, his temperature was 99°, pulse 82, weight 217 pounds. The condition in both lungs was markedly improved. There were a few scattered rales throughout the lungs but the principal involvement was confined to the area surrounding his cavity in the left lung. The patient was in good general condition, and able to take long walks without tiring. Three months after his discharge from the sanatorium he consulted me again in my city office. At this time the condition in the lungs was about the same, his general condition was good, but he was suffering from a brachial neuritis on the left side. The pain was quite severe, prevent- ing him from sleeping, and also interfering with his rest during the day. The muscles of the left arm gradually atrophied and the strength in the arm was very much reduced. This neuritis persisted for several months almost totally disabling the patient. PATHOLOGY OF PERIPHERAL NEURITIS 167 It is important to note that the brachial neuritis is on the same side as his severest involvement. Pathology of Neuritis in the Tuberculous. — According to Hezel, the most common pathological change found in the nerves of the tuberculous is a parenchymatous degeneration. The nerve filaments degenerate and atrophy while the axis cylinder re- mains intact. In this early stage of degeneration no clinical symptoms are manifest. In the later stages of degeneration, not only the nerve filaments, but also the axis cylinder is in- volved and conduction is interfered with and later may be wholly lost. The sheath of Schwann and the endoneurium show certain alterations but nothing that can be considered as genuine in- flammatory changes. In certain nerves Wallerian degeneration takes place. In a few instances which have been critically examined the ganglion cells of the anterior horn as well as the special ganglia of those segments of the cord from which the nerves, which were the seat of neuritis, took their origin, showed histological changes in the way of different degrees of chromatolysis. These changes were more pronounced in the ganglion cells of the anterior horn than they were in the cells of the spinal ganglia. Steinert 11 found degeneration in the ascending fibers of the spinal cord. The long fibers of the posterior column of the cord were degenerated. This was most marked in the cervical por- tion of the cord and confined to the posterior columns of Goll, the fibers of the posterior column which take their origin in the lumbar and sacral segments of the cord. The degeneration of the ganglion cells in Steinert 's cases was in the sacral and lumbar portions of the cord, the portions from which the dis- eased peripheral nerves took their origin. Jessen 12 in his splendid monograph and Hezel 13 in a later dis- cussion cites the reports of many observers showing a varied clinic and pathology in nervous diseases, in which the tuber- culous process itself seems to be the causative factor. Jessen quotes Heine as finding degenerative changes in the phrenics in 27 of 29 patients examined and Japp as finding changes in the peripheral nerves of every one of 15 cases. M Zur Kenntnis der Polyneuritis der Tuberkulosen, Beitrage zur Klinik der Tuber- kulose, vol. ii, 1904. "Lungenschwindsucht und Nervensystem, Gustav Fischer, Jena, 1905. "Tuberkulose und Nervensystem, in Brauer, Schroder und Blumenfeld, Handbuch der Tuberkulose, Bd. iv, 1914. CHAPTER VII. THE NERVOUS SYSTEM CONTINUED: THE VEGETATIVE NERVOUS SYSTEM IN ITS RELATIONSHIP TO DIS- EASES OF THE LUNGS: A DISCUSSION OF PRINCIPLES, INCLUDING THE ANTAGONISTIC ACTION WHICH IS MANIFESTED BETWEEN THE GREATER VAGUS AND SYMPA- THETIC DIVISIONS. Joint Chemico-physical Sensorimotor and Psychical Control. — In our physiological studies the point is emphasized that every cell and every activity of the body is under the direct control of the nervous system and subjected to many reflex influences. This is true, but we must not forget that there are psychical and chemical controls which are of equal importance. Many viscera produce secretions which have been given the name of internal secretions because they are not delivered from the gland through special ducts, with which the gland is pro- vided ; but are contained in the venous blood as it emerges from the gland. These internal secretions have selective action; and, through them, one organ may be able to control or influence an- other organ far distant in the body. This may be illustrated by the action of adrenin, and the secretion of the thyroid gland, both of which exert influences upon cells and other structures through- out the body. Other glands produce important secretions which have a more selective action. All must work normally if har- monious physiological action is to be maintained throughout the body. A disturbance in one has a tendency to produce disturb- ance, either selective or general in others, the same as is pro- duced reflexly through the nervous system. It is impossible to definitely separate the chemical from the nervous control of the body cells. Owing to our paucity of knowledge, we are prevented from drawing absolute conclusions and putting the nervous and chemical control on an absolutely scientific basis. THE VEGETATIVE NERVOUS SYSTEM 169 In any study that is to be made of the vegetative nervous sys- tem, the clinician can only point out that such an action is the one that would be expected under a given condition. The re- sultant action, however, may be modified or prevented, by other factors, such as those produced through an antagonistic reflex, through chemical control, or through psychical or physical in- fluences. In this connection we must not forget the psychical control of the human body. The subconscious mind is always active, not only influencing but determining our action and conduct, and also influencing our physiological activities. This important field is one that deserves further study, and promises to help us ex- plain many conditions which cannot be explained on a purely physical basis. The Vegetative Nervous System. — Vegetative, autonomic, and involuntary are all terms used to designate that portion of the nervous system which acts without the interposition of the will. This system furnishes impulses for carrying on the particular functions of the body which are necessary for the preservation of life. The writer has been greatly stimulated in this study by the works of Eppinger and Hess, 1 Walter B. Cannon, 2 Wm. H. Gas- kell, 3 Heinrich Higier, 4 W. v. Bechterew, 5 S. C. Sherrington, 8 Lewandowsky, 7 Arthur Keith, 8 Biedl, 9 E. A. Schafer, 10 Chas. E. de Sajous, 11 E. H. Starling, 12 W. M. Bayliss, 13 and contributions by Professor E. G-ley, Noel Patton, T. R. Elliot, and Swale Vincent, in the Practitioner's special number on " Internal Secretions." 14 There is so much confusion in the terminology of this system 1 Die Vagotonic, Sammlung Klinischer Abhandlungen, von Noorden, Heft. 9 u. 10, 1910. 2 Bodily Changes in Pain, Hunger, Fear, and Rage, D. Appleton & Co., New York, 1915. 3 The Involuntary Nervous System, Longmans, Green & Co., New York, 1916. 4 Vegetative or Visceral Neurology, Ergebnisse der Neurologie und Psychiatrie, Bd. ii, Heft 1, 1912. °Die Funktionen der Nervencentra, vol. i, Gustav Fischer, Jena, 1908. "The Integrative Action of the Nervous System, Charles Scribner & Sons, New York, 1906. 7 Die Funktionen des zentralen Nervensystems, Gustav Fischer, Jena, 1907. 8 Human Embryology and Morphology, Edward Arnold, London, 1913. "Innere Sekretion, Urban und Schwartzenberg, Wien, 1910. 10 The Endocrine Organs, Longmans, Green & Co., New York, 1916. n The Internal Secretions and the Principles of Medicine, F. A. Davis and Company, 1903. 12 Principles of Human Physiology, Lea and Febiger, 1915. "Principles of General Physiology, Longmans, Green & Co., New York, 1915. "Practitioner, London, 559, vol. xciv, 1 and 2, January, 1915. 170 NERVOUS SYSTEM IN TUBERCULOSIS and its divisions that it is necessary for each writer to make clear at the beginning of his discussion the meaning of the terms as he employs them. Throughout my discussion, I shall speak of the entire involuntary system as the vegetative system; and its divisions as the sympathetic system, comprising the motor cells which have pushed off from the thoracic and upper lumbar portions of the cord; and the greater vagus system, comprising the motor cells which have pushed off from the cranial, bulbar, and sacral portions of the cord. I deem it best to follow the terminology of Eppinger and Hess in calling the latter group the "greater vagus" system because of the fact that all cells belonging to these groups possess the common property of antagonism to the sympathetic system. The greater vagus is often spoken of as the autonomic system (Jel- liffe and White), in contradistinction to the sympathetic; but, inasmuch as this term is also applicable to the vegetative system as a whole, I think it advisable to refrain from applying it to one of the divisions. In order to obtain a correct idea of the vegetative nervous system one must understand that the cells of this system have traveled out from the central nervous system. Very early in em- bryonic life before the neural folds have closed to form the spinal cord, these neuroblastic cells migrate. They are deposited here and there and form, for the most part, the ganglia of the vegeta- tive system. Some of the neuroblastic substance, however, is de- posited in other places, and this is known as chromaffin tissue; because, when stimulated, it secretes a material which stains brown with chrome salts. Physiologically, we know this secreted substance as adrenin or its immediate precursor. The cells which migrate from those portions of the central nervous system which give origin to the greater vagus fibers do not come to rest until they are situated in the walls of the viscera to be innervated by them. Here they form ganglia and throw out their processes which furnish motor and secretory fibers. They are connected with the central nervous system by connector fibers belonging to the greater vagus system, as il- lustrated in Plate I from Gaskell, which run from the centers in the cranial, bulbar, and sacral portions of the central nervous system directly to the ganglia in the walls of the viscus sup- DNX NI NM DNX B X Y M A Plate I. — The Reflex Paths in the Bulbar Region. {Green — Sensory nerve; receptor neuron. Black — Connector neuron. Red — Motor nerve; excitor neuron.) A. Of the Somatic System. The afferent neurons run in the fifth nerve, V, their cells lying in the gasserian ganglion, GG. These connect with the connector neurons lying close against the descending root of the fifth nerve, DSV. The connector neurons in their turn connect with the excitor cells which lie in the nucleus of the twelfth nerve, NXII. B. Of the Splanchnic System. The receptor neurons run in the tenth nerve, X, with their cells lying in the ganglion of this nerve, VG, and connect with connector neurons which lie in the dorsal nucleus of the vagus, DNX. Processes of the connector cells con- nect with the excitor neurons which lie in the nucleus ambiguus, NA, their proc- esses form the motor part of the tenth nerve. C. Of the Involuntary System. The receptor neurons run on the tenth nerve, X, with their cells in the ganglion of this nerve, VG, and connect with connector neurons which lie in the nucleus intercalatus of Staderini, NI, which forms a part of the dorsal nucleus of the vagus, DNX. The processes of these connector neurons run out in the vagus nerve, X, and finally connect with the excitor neuron which lies on some peripheral organ; e.g., in the case of the intestine lying in Auerbach's plexus, AP. (Gaskell.) VEGETATIVE NERVOUS SYSTEM 171 Tear Gland. 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In inflammations of the in- ternal viscera, whatever irritation is present probably, as mentioned later, influences both vagus and sympathetic filaments peripherally and causes them to stimulate structures reflexly. It is interesting to note that toxemia, and the depressive emotional states such as fear, anxiety, discouragement, worry, and disappointment, are accompanied by the same symptom- complex. This is particularly easy to recognize in tubercu- losis, because it is a disease which manifests so many periods of slight activity accompanied by a low or moderate degree of toxemia, which disappears after a few days' duration; and, be- cause it is likewise accompanied by so many of the depressive emotional states, which come and go as the causes which pro- duce them come and go. The symptoms of toxemia and of the depressive emotional states are: headache, malaise, nervous irritability, insomnia, lack of appetite, coated tongue, inhibition of gastric and in- testinal secretion and motility, constipation, fever, pallor, and, at times, sweating. The above symptoms are not constantly present, nor do they manifest themselves in equal degree in each organ innervated by the sympathetic system. They are sufficiently constant, however, to indicate that they are a result of a central stimu- lation of the sympathetic system. The variability of the symptoms caused by central stimula- tion of the sympathetics in pulmonary tuberculosis is due to the fact that peripheral reflex stimulation of the pulmonary nerve endings of both the vagus and sympathetic is also pres- ent whenever activity in the pathological process is sufficiently acute to produce toxemia. It is possible; in fact, I have often observed that the reflex peripheral stimulation of the vagus was sufficiently strong to overcome both central and peripheral stimulation of the sympathetic. This I have seen manifested 190 NERVOUS SYSTEM IN TUBERCULOSIS in one or more of the following ways: a moist clean tongue, a hyperacidity, or a relatively slow pulse, during periods of acute toxemia accompanying cavity formation in the lung. After the acute activity passes over, unless the patient is prolonging the toxemia by wrong methods of living, particularly overexertion; or is suffering from such depressive influences as worry, fear, and discouragement, the central stimulation of the sympathetics ceases and whatever symptoms, arising from the nervous system, remain, are due to the irritation of the nerve endings by the inflammation in the lung, and are ex- pressed as reflex phenomena in other viscera. There is no question that peripheral stimulation of the greater vagus, in one of its branches, will result in stimulation and the production of vagus effect in the other branches of the greater vagus. Stimulation in the intestine causes slowing of the heart; stimulation in the uterus, ovary, or testicle causes vomiting; and, stimulation of the vagus in the nasal mucous membrane will cause bronchial spasm or asthma. Whether the same is true of the sympathetics is open to ques- tion. Sensory paths in the sympathetics are supposed to take the same course as in the spinal nerves. The nerve cells for them lie in the posterior root ganglia of the cord; and the path is sup- posed to be uninterrupted by ganglia. Thus, Gaskell 20 says: "All the afferent fibers have their nutrient centers in the posterior root ganglia. No peculiarity, therefore, exists on the afferent side; the course of the sensory fibers is the same in all sensory nerves, viz. : direct to the cells of the posterior root ganglia, with no connection with any cells in sympathetic ganglia." If this is true, then we are wrong in supposing that peripheral irritation of the sympathetic fibers in one viscus can cause reflex action in some other viscus except the impulse be carried to the cord, there to be transferred from the posterior root ganglion to the anterior root and through the connector fibers to the motor cells in the sympathetic ganglia of the same segment, whence it is transmitted to the viscus. Beehterew 21 says: "The functions of the sympathetic nervous system are divided, as is well known, into sensory, motor, secretory, and trophic. The 20 The Involuntary Nervous System, Longmans, Green & Co., New York, 1916, p. 17. 21 Die Functionen der Nervencentra, Gustav Fischer, Jena, 1908, pp. 59-60. SYMPATHETICS AND VISCERAL REFLEXES 191 sensory sympathetic fibers transmit impressions to the spinal cord and brain ; the motor supply the involuntary or unstriped muscu- lature. Aside from this, there are mixed fibers which establish a connection between neighboring sympathetic ganglia. The tonus of unstriped muscle fibers is reflexly maintained through sympathetic ganglia. The sympathetic system is also, without doubt, operative in originating many reflexes in the sphere of the internal organs. "There is lacking today scarcely a single proof of the fact that cellular interruption of nerve fibers takes place in the sympathetic ganglia. With this fact established these ganglia assume at once the role of true nerve centers. It follows as a consequence from the proof of interruption as produced by Eamon Y. Cajal that the nature and manner of the relationship between nerve fibers and nerve cells in the sphere of the sympathetic system is in reality the same as in the spinal and cerebral portions of the central nervous system." It seems to me that we are obliged to assume the truth of this position with reference to the reflex relationship of the internal viscera through the sympathetics. It is the only way that we can account satisfactorily for the symptomatology of disease of the internal viscera. If this is not true, then we must consider that the only way in which an inflammatory process in one viscus can influence another viscus through the sympathetics is by producing substances which gain entrance to the circulation and cause central stimulation of sympathetic cells as in case of the various toxemias, or peripheral stimulation as in the case of adrenin. It precludes the possibility of such definite reflexes affecting internal viscera as those that we encounter in the branches of the greater vagus. In my discussion of the reflex symptoms found in tubercu- losis and the antagonistic action manifested between the great- er vagus and sympathetic in their production, it will be neces- sary for the reader to bear in mind that there is this doubt as to whether the sympathetics are able to produce a true reflex, which shows in other viscera without mediation in the spinal cord. There is no doubt however, as to the influences which are 192 NERVOUS SYSTEM IN TUBERCULOSIS present, stimulating the sympathetics now centrally, now periph- erally, and increasing the general sympathetic tonus. This at times overcomes the vagus tonus, and at other times is over- come by the greater vagus. In my previous papers I followed the assumption that peripheral stimulation of the sympathetics causes reflex action in other viscera; but, while clinical facts seem to warrant this, it is best to consider it as still subject to doubt. In pulmonary tuberculosis after all conditions which ef- fect general central or peripheral stimulation of the sym- pathetics seem to have been removed sometimes the tonus is greater in the vagus system, at other times in the sympa- thetic. As a rule, however, except during periods of increased toxemia, which I shall discuss later, my observation leads me to believe that the vagus tonus is greater than the sympathetic tonus in early tuberculosis. This is shown on the part of the heart, and particularly on the part of the gastrointestinal tract. There are many exceptions to this, however, especially among those congenitally weak and those, in whom sympathetic tonus predominates naturally. In estimating the relative tonus of the vagus and sympathetic systems it is necessary to bear in mind that increased tonus might show in one division of the nerves and not in all, and that this increased tonus in particular divisions might not be constant. This variability is due to the fact that there are many factors acting at the same time which cause stimulation and that some of these have selective action for certain struc- tures. This is not only evident in the reflexes but also in the internal secretions which affect the two systems. It is also evident from the fact that the tuberculous patient may have increased or decreased tonus in either the vagus or sympathetic system from causes other than those which operate as a result of the pulmonary infection. Because of the antagonistic action of the vagus and sympa- thetic systems the function of many organs is rendered unstable when an unequal stimulation of one or the other occurs. The heart, while at rest, is often slower than normal, but on exer- tion, or during periods of toxemia or depression at once be- ALTERNATING VAGUS AND SYMPATHETIC TONUS 193 comes more rapid than normal and settles down to the normal much slower than it should. The appetite, while disturbed dur- ing conditions which favor increased absorption of toxins such as exertion, or during periods of increased activity in the tu- berculous foci, or during periods of depression and worry, is often normal and even above normal when the patient is put at rest in the open air under favorable circumstances which offer him hope of cure. The same is true of the gastric and intestinal functions. Hyperacidity and hypermotility are the rule in early tuberculosis, when toxemia is relieved. The intestinal tract also shows the same increased tonus. The vagus system, the one which if slightly in the ascendency, conserves the healthful action of the important internal organs, overcomes its antagonist in early tuberculosis for the most of the time and this offers the patient an increased opportunity for restoration to health. If vagus tonus is marked, however, it proves harmful. During waves of increased activity in the tuberculous focus, however, and during the period when the patient is causing in- creased absorption of toxins by overexertion and other faulty habits, likewise during periods of great depression from other causes, the excessive stimulation of the sympathetic produced by both reflex action and emotional states overcomes the increased vagus tonus and causes symptoms which are characteristic of sympathetic irritation, such as sweating, rapid heart, decreased appetite, hypochlorhydria, deficient gastric motility, and altera- tion in the secretion and motility of the entire intestinal tract. Aside from the antagonistic action of these two systems it seems probable that antagonistic fibers are at times supplied to organs by the same system. In health a state of equilibrium is maintained in the various organs as a result of the antagonistic action of these two systems. In any disease which affects either by stimulation or by setting aside the normal nerve tonus of any important branch or group of fibers of either or both of these systems, there is a conse- quent disturbance of equilibrium which results in a pathologi- cal state. This is evident in the production of nausea through eye strain, or the slowing of the heart in abdominal lesions which affect the 194 NERVOUS SYSTEM IN TUBERCULOSIS depressor fibers of the vagus. So it is evident in pulmonary inflammation. Effect of Internal Secretions on Symptomatology. — Aside from the direct stimulation of the nerves by inflammatory processes we must recognize the influence of substances of a chemical nature which act either upon terminal filaments or nerve centers. Thus the primary action of toxins is upon the central cell bodies. A secondary action may be a totally different one and depend on certain secretions which are set free as a result of the pri- mary toxic influence, such as occurs when adrenin is set free by certain emotional states or gastric secretion is stimulated by the smell or taste of savory food. No doubt future study will clarify this subject very much by the discovery of the true relationship which exists between many of the internal secre- tions and the structures controlled by them. Internal Secretion of the Thyroid. — At this point of our dis- cussion it might be well to call attention to the enlargement of the thyroid gland, which occurs commonly during early clinical tuberculosis. I realize that the tendency of scientific opinion of today is toward the theories of insufficient iodine being ob- tained by the individual and that of infections being the causa- tive factors in enlargements of the thyroid gland. I cannot help believing, from my own experience, however, that a hyper- plasia of the thyroid gland takes place in the presence of toxemia, where no infection of the gland itself occurs. This can be rationally explained, now that we have the works of physiologists (Cannon), which show that sympathetic stimulation increases thyroid secretion. When toxemia is present, as I have discussed fully throughout this monograph, there is a general sympathetic stimulation. One of the results of sympathetic stimu- lation is increased action of the adrenal gland. If adrenin stimulates the thyroid, it is but natural to suppose that increased adrenin calls for increased flow of thyroid secretion. It is a principle in physiology that increased function, not only of muscles, but ,of secreting organs, is accompanied by increased blood to the part, and increase in the size of the cellular com- ponents; consequently, it is not at all beyond reason to suppose that these enlargements of the thyroid gland, which occur in OVARIAN SECRETION 195 early clinical tuberculosis, and which are also noted when we have infections in other parts of the body, such as the tonsil and nasal sinuses, might be due to a hyperplasia of the gland, re- sulting from increased stimulation. That this explanation is plausible is further implied in the fact that the gland returns to normal after the toxemia disappears. Internal Secretion of the Ovary. — It is also well to bear in mind the influence of the internal secretion of the ovary in the production of the premenstrual rise in temperature. I have sug- gested, as an explanation of this phenomenon, that it represents a stimulation of the vasomotor center which acting through the sympathetic system, causes vasoconstriction and interference with the dissipation of heat (see Chapter XXX). The nervous phenom- ena which occur at the menopause when the ovarian secretion ceases are undoubtedly largely those of disturbed nerve balance and particularly that of increased vagus tonus ; and further indi- cate that the internal secretion of the ovary acts by stimulating the sympathetic nervous system. The premenstrual nervous dis- turbances which so commonly complicate our symptom-complex in tuberculosis become more intelligible with the understanding of their causation. Symptoms Appearing at the Menopause Due to the Cessation of Ovarian Secretion. — The menopause is usually considered as a critical period in woman's life. It is a time when the normal resistance seems lessened, therefore it is of great interest to the students of tuberculosis. It has long been known that at that time a general atrophy of the female generative organs takes place; but the manner in which this acts to produce the symptoms noted has not been thoroughly understood. At this time instability of the nervous system is the most prom- inent symptom. With more accurate clinical observation and our increasing knowledge of the action of the glands of internal se- cretion, this condition becomes more understandable. As puberty comes on, ushering in the child-bearing period, very marked changes take place in both the physical and nervous make-up of the individual. In this new period of woman's life there is one particular new force added to those which have been previously operative; namely, the internal secretion produced by the sex 196 NERVOUS SYSTEM IN TUBERCULOSIS glands, particularly the ovary. The ovarian secretion acts upon the sympathetic nervous system and stimulates all structures supplied by it. Consequently there is a stimulation of certain other glands of internal secretion, — such as the adrenal gland, stimulation of which causes increased oxidation; and the thyroid gland, stimulation of which causes increased metabolical activity. The action upon these two glands of internal secretion is most evident, clinically, but doubtless the influence of this secretion is felt generally; because we cannot conceive of any new potent force coming into the chain of internal secretions without dis- turbing the established equilibrium in all. The disturbance of this equilibrium is not continuous during the child-bearing period, but is most marked during the period of ovulation. This causes the cycle in woman's life which has been clinically observed throughout the child-bearing period. It would seem that the ovarian secretion is given into the blood stream ir- regularly even in the same individual and that its influence upon the system is much greater in certain individuals than in others. In observing many cases of pulmonary tuberculosis over pro- longed periods of time, I have noticed the influence of this secre- tion as it expresses itself in the nervous system. The manner in which it influences the pulse and temperature is shown in clinical charts which are given throughout these pages, and may be particularly studied in patients whose temperature and pulse curves are shown over a long period of time in "The Tubercu- losis Clinic," Chapter L, Vol. II. It will be noticed that in some patients this influence shows with almost absolute regularity month after month. It may be possible that the internal secretion of the ovary is given off con- tinuously; but it is given off in greater quantities in most in- dividuals during the two weeks preceding menstruation. At times its influence is seen on the 14th day following menstruation and shows as a slight rise in temperature, which continues until the day of menstruation when it drops again. Sometimes the pulse will also show an acceleration. In others this may not be noticeable. My observation has been that acceleration of the pulse is not as general as the elevation of temperature, but that it occurs most commonly when marked nerve irritability is pres- MENSTRUAL CYCLE AND MENOPAUSE 197 ent. Menstruation is also preceded by a rise in blood pressure, and accompanied by a fall in pressure. When marked nerve stimulation is present, it manifests itself in such symptoms as insomnia, depression, disturbed appetite and increased irritability. These symptoms are more marked as a rule only a day or two preceding menstruation. According to my observation, this pre-menstrual rise in temperature may come on any time from the 14th day prior, up to the day of menstruation it- self. In a few instances it would seem that the ovarian secre- tion does not affect the patient prior to menstruation but only dur- ing the same and probably for a few days following. In these cases there seems to be a reverse curve. This will be noticed in some of the charts in these pages (see Fig. 128, Vol. II) ; but this is infrequent. We assume that the stimulation of the sympathetic is coincident with ovulation, and are fortified in this assumption by the fact that all symptoms of sympathetic stimulation disap- pear when the menopause has been passed. During the child-bearing period the organism gradually ac- customs itself to the ovarian secretion and its stimulating effect upon the nervous system. The effect of any sympathetic stimula- tion if counterbalanced at all, is counterbalanced through stimula- tion of the vagus. It is probable that in many individuals the ovarian secretion is so slight in its influence that its action is within the bounds of sympathetic and vagus balance; but where the nervous stability is threatened by the influence of the ovarian secretion, equilibrium may be maintained by some natural physio- logical force which is able to counteract the sympathetic influence. When the necessity for further ovulation ceases, the ovarian secretion also ceases. The result is a marked unbalancing in the nervous system. The picture on the part of the vegetative system is that of marked instability, the vagus influences, for the time, being in the ascendency. Not only the vegetative nervous sys- tem but the central nervous system and psychical control are often disturbed. So this is a period when woman is required to ad- just herself to new conditions. Our conception of the etiology of symptoms which accompany the menopause, are: 1. A withdrawal of the ovarian secretion from circulation. 198 NERVOUS SYSTEM IN TUBERCULOSIS 2. The elimination of the normal stimulation of the sympa- thetics produced by the ovarian secretion, which results in a dis- turbance of balance in the vegetative nervous system, permitting vagus tonus for the time being to be in the ascendency. 3. A disturbance on the part of the higher nerve centers as a result of the general disturbance in the vegetative system; and possibly also directly as a result of the absence of the action of the ovarian secretion on the higher centers. 4. A general psychical instability resulting from the height- ened irritability of the vegetative system and the higher nerve centers. . ANTAGONISTIC ACTION OP GREATER VAGUS AND SYMPATHETIC AS SHOWN IN SYMPTOMS OF PULMONARY TUBERCULOSIS. Let us now proceed to apply the principles involved in the stimulation of the nerves of the vegetative system to pulmonary tuberculosis and the explanation of such phenomena as are caused by the disturbed balance in the vagus and sympathetic systems. In tuberculosis we must conceive of a condition in which both the vagus and sympathetic systems are simultaneously stimu- lated, but one in which either one or the other usually yields with a resultant disturbed equilibrium. Dilated Pupil. — At least 50 per cent of tuberculous patients show a dilated pupil on the side of the involvement during some time when the inflammation is acute; and it is probable that a much larger per cent would show it if observation could be made continuously. This indicates that the action of the sym- pathetics overcomes that of the vagus. This dilator effect is due to irritation of the fibers from the first and second thoracic segments of the cord. Artificial stimulation of these fibers causes the same dilator effect. Aside from the disturbances in the pupil the ciliary body is stimulated to contractions by irritation of the vagus. I am inclined to believe that there is often a serious disturbance of accommodation in tuberculous patients due to the unequal stimulation of the pulmonary ends of the vagus and sympathetic. It is surprising to see how many patients com- VEGETATIVE SYSTEM AND SYMPTOMATOLOGY 199 plain of headache if they continue to use their eyes for reading, knitting, or sewing, as they have been accustomed to do prior to their illness. They also seem to show an increased sensitive- ness to bright light and I often find it necessary to suggest that the bed be so placed that the light will not shine directly in the eyes. Change of eye glasses is made necessary more often than prior to illness even in early and chronic cases which are only slightly active. Hectic Flush. — The exact explanation of hectic flush is some- what vague. Why there should be a dilation of the vessels of the face and ear when the sympathetics supplying them con- tain both dilator and constrictor fibers, as determined by arti- ficial stimulation, can be answered only by assuming that the natural stimulant in tuberculosis has a peculiar affinity for the dilators; or, that it paralyzes the constrictors. The constrictor tone of the vessels of the mouth, cheek, ear and head is main- tained through the superior cervical ganglion by fibers which re- ceive their stimulation from the connector nerves arising from the first, second, third, fourth and fifth thoracic segments (maximum effect coming from second, third and fourth), and in the case of the ear, the third cervical. The dilator effect seems to be due to either an affinity for the dilators or an overstimulation of the constrictors resulting in their exhaustion. A clinical observation, which seems to corroborate the latter supposition, is that hectic flush does not appear early in tuberculosis. It nearly always appears coinci- dent with marked clinical activity; so, it would seem that there exists not only a stimulation of fibers somewhere in their course, but also a central stimulation produced by the toxins in order to overcome the constrictor and produce the dilator effect. Heart. — In the heart in tuberculosis we have so many condi- tions present which influence the pulse rate that it is impossible to accurately ascribe to the vagus and sympathetic systems the part which each plays. Impulses are carried through both sys- tems, because both are constantly irritated. As a result of this double source of impulses, the one through the vagus tending to slow the heart, the other through the sym- pathetic, attempting to quicken its action, there is a marked 200 NERVOUS SYSTEM IN TUBERCULOSIS 5 2 VARIABILITY OF HEART BEAT 201 disturbance of equilibrium. This shows early in the disease be- fore such conditions as loss of pulmonary tissue, heart strain, and degenerative changes can be considered. The heart beat may be normal, slower than normal, or only slightly faster than nor- mal while the patient is at rest ; but it is often unduly rapid on exertion, and returns to normal slower than in the healthy individual. This relative slowness of the heart beat is often noticed during periods of temperature, as compared with the same degree of temperature in other diseases. This is unquestionably the result of an inhibitory reflex through the vagus, the impulse coming from the irritation in the lung. When the intestinal tract is af- fected with tuberculosis, then another division of the greater vagus system is stimulated and we often see this inhibitory ac- tion accentuated, with still greater departure in pulse rate from that which would be expected with the degree of temperature present. If an unusual slowing of the pulse occurs in the course of pulmonary tuberculosis, coincident with an elevation of one or two degrees in the temperature curve, reflex vagus irrita- tion should be considered as a probable cause and a complicat- ing intestinal tuberculosis be suspected. These vagus influences are seen very often clinically, as shown in the following charts: Fig. 29 is the chart of a patient suffering from moderately ad- vanced tuberculosis, but in whom toxemia was a very small factor. It will be noted that the temperature which was between 99° and 100°, on entering the institution dropped to practically normal after 10 days' rest. The pulse was found, as a rule, be- tween 60 and 70. This patient's resisting power was good and his chances of recovery splendid, in spite of a widespread lesion. This patient was markedly vagotonic. Fig. 30 shows the pulse of a patient suffering from very exten- sive inflammation of the right lung, which went on to the rapid formation of fibrosis, and eventually resulted in arrestment. This case is described in Volume II, Chapter L, Case 2,514. It will be noticed that while the temperature was ranging above 102° the pulse was not exceeding 100 beats per minute. Toward the end of the month a very interesting condition presented it- 202 NERVOUS SYSTEM IN TUBERCULOSIS H3 p a 6.2 SS B^ 60.3 ■rt d > ft O « III S £ D bo C a £ bnii o « 3,0 c O.JJ *s 210 NERVOUS SYSTEM IN TUBERCULOSIS we must look upon the pulmonary involvement as being the de- termining factor in causing this low pulse. See pages 204 and 205. Irritation of other branches of the vagus will also cause inhibi- tory action upon the heart. Pressing upon the eyeball and irri- tating the nasal mucous membrane will both cause slowing of the heart. Opposing this inhibitory action of the vagus is the accelerating action of the sympathetics, either through central stimulation by toxins; stimulation by the various emotional states which af- fect the patient ; stimulation by certain internal secretions which result when the sympathetics are stimulated or other factors which call for accelerated blood now. Often the sympathetic ir- ritation gains the upper hand and a markedly rapid pulse re- sults. Fig. 33 illustrates the manner in which the pulse as well as the temperature is influenced by toxemia. This chart is that of a patient who is suffering from moderately active tuberculosis. The course of the disease was interrupted at periods of from two to four or six weeks, with a high temperature. During each one of these rises in temperature there was an increase in pulse rate corresponding with that in the temperature curve. This is il- lustrated with the rise of temperature which started on the 6th of the month and culminated on the 9th. It will be noticed how the gradual increase in temperature and pulse rate followed each other. See page 207. Figs 34 and 35 illustrate a marked disproportion between the degree of temperature present and the pulse rate ; the pulse being very high considering the temperature curve. These patients were both nervous patients; and, while not inclined to worry, they were in a constant state of disturbed nervous equilibrium, which manifested itself upon the pulse. They both belong to the type of individuals with increased sympathetic tonus. See pages 208 and 209. Figs. 36, A and B, are charts which illustrate sympathetic ir- ritation in a patient who naturally is markedly vagotonic. This patient suffered from rather a widespread lesion in the right lung, which made satisfactory improvement. These are the early charts in the case. It will be seen in chart A that the tempera- ture was ranging between 99° and 100°. The pulse during the VEGETATIVE NERVOUS SYSTEM AND SYMPTOMS 211 first half of the month remained between 70 and 80, and dropped into the sixties. On the 14th of October this patient began to show marked signs of nervousness. She became exceedingly de- pressed, discontented, and unhappy. The effect is seen on the pulse. Without further elevation in temperature the pulse in- creased in rapidity, and, on several occasions, reached a maximum of 100°. This increased sympathetic stimulation occurred during the two weeks preceding the menstrual period and was probably induced by the action of the ovarian secretion upon the sympa- thetic nerves. It will be noticed that in chart B the pulse came down into the seventies; but, on the 8th of November, showed another elevation, which continued until the 21st. The sympa- thetic stimulation this time was not so marked. The difference was partly due to the fact that I had explained to this patient why she felt nervous and discontented, and, with this under- standing, she was able to prevent a great deal of the depression which had manifested itself the previous month, and which had manifested itself more or less frequently throughout her men- strual life. See pages 212 and 213. Intestinal Tract. — The antagonistic action of the vagus and sympathetics on the different portions of the intestinal tract is ex- tremely interesting; and our understanding of this action will aid greatly in forming an accurate clinical conception of the di- gestive capabilities of the tuberculous patient. Early in tuberculosis the toxemia present is not of a high de- gree, and its action upon the sympathetics is negligible, as com- pared with that present in the more advanced cases. From the very first, however, vagus stimulation seems to be important. This is shown in the larynx, in hoarseness due to interference with the innervation; in the irritation which produces cough, and in the increased bronchial secretion. It is likewise marked in the intestinal tract as I shall now proceed to describe. Influence on the Salivary Flow. — During tuberculosis, some- times there is an increased amount of saliva and, at other times, there is a decrease. These changes show more particularly in some patients than in others. There is a double secretory nerve supply to all the buccal secretory glands, the parotid, submaxil- lary, sublingual, and retrolingual glands. Stimulation of either 212 NERVOUS SYSTEM IN TUBERCULOSIS a S a a en n! i-, 3 ° G o rt (U rt 3 H a, >> eft V ttf! * M C u-i ct) >> •^ o fe T3 SYMPATHETIC TONUS SHOWN IN PULSE 213 Sfi J bo c u 43 bf C , , si rt u a 3 J=l Cq'S boji> 214 NERVOUS SYSTEM IN TUBERCULOSIS the chroda tympani, or of the superior cervical ganglion will in- crease the salivary secretion. It would seem that, clinically, the greater vagus must be the more important secretory nerve because the toxemia which stimulates the sympathetic, also the atropin which inhibits the action of the greater vagus produces dryness of the mouth. Tongue Atrophy. — The base of the tongue is supplied by vagus fibers which pass through the glossopharyngeal (ninth cranial) nerve. As a result of prolonged chronic inflammation in the lung these tissues atrophy and when the tongue is protruded it may be pushed to the side. I have long noted this fact clinically. It can be best determined in a markedly one-sided chronic lesion. When the symptom is present the tongue pushes toward the side of the more chronic and more destructive lesion. Motor and Sensory Disturbances in Pharyngeal Structures. — Patients suffering from chronic pulmonary tuberculosis suffer from reflexes which affect the pharyngeal tissues. The vagus supplies the mucous membrane with sensation and the constrictor fibers with motor power. These fibers when reflexly disturbed may show either sensory or motor phenomena. The increased sensitiveness of the pharynx which is particularly noted when a pulmonary process is acute, as during necrosis and cavity forma- tion may be accounted for in this way. During this time cough is frequently followed by retching and vomiting. Irritation of the pharynx takes place very easily and is followed by a further vagus reflex, — vomiting. The ease with which the vomiting reflex may be exerted by tickling the pharynx is well known ; and when hypersensitive, the reflex phenomena follow the more readily. A motor reflex in the pharyngeal muscles is often noted late in the disease. The pharyngeal muscles atrophy the same as other structures whose central cell bodies are in reflex connection with chronic constant stimulation. This manifests itself in an irritated condition of the nerves which show as vague pains and in an atrophy of the muscles and occasional disturbance in the act of swallowing. Coated Tongue. — A dry coating of the tongue is often noticed during periods of temperature in cases where toxemia is a factor. SYMPTOMS AND VEGETATIVE NERVOUS SYSTEM 215 The drying effect on the salivary secretions through the sympa- thetics must be thought of as an etiological factor. The fact that this is nearly always accompanied by a diminution of appetite and deficiency in gastric and intestinal efficiency makes the cause the more probable, for these other conditions are likewise due to deficient vagus tonus or increased sympathetic tonus. When toxemia has passed over, on the other hand, a normal tongue, and even increased appetite, may be seen. Stomach. — The disturbances on the part of the stomach in early tuberculosis are those which belong to the class of so-called nerv- ous dyspepsias. The form which seems most common, except when the patient is suffering from toxemia or mental depression, as I shall describe later, is hyperacidity. This is a reflex through the vagus, the reflex coming from the inflamed pulmonary parenchyma. At first the patient's digestive powers are, if any- thing, above par. This is one reason why the tuberculous patient is able to care for such large amounts of food. Associated with increased secretion there is often an increased motility. This shows itself now and then in a feeling of nausea and tendency to vomit. These conditions, however, are not continuous. The increased vagus tonus can be relieved by the administration of atropin; and, following its administration, hyperacidity and hy- permotility often disappear or are ameliorated. There are also several factors which come in to cause sympa- thetic stimulation and inhibition of the vagus action, noticeably, toxemia and the depressed nervous states which are so common and which are characterized by mental depression, discourage- ment, and fear. These emotional states come and go through the disease. They are sometimes dependent upon and sometimes in- dependent of toxemia. Intestines. — A similar condition obtains in the intestinal tract where we have states of increased vagus tonus, causing increased secretion and increased motility, and abnormal sympathetic irrita- tion inhibiting this action and interfering with secretion and peri- staltic action. Spastic constipation as a result of increased vagus tonus is common in early tuberculosis, while the atonic type is the rule later. Definite effects of each system are not so easy to point out in 216 NERVOUS SYSTEM IN TUBERCULOSIS the intestinal tract because of the preponderance of stasis and constipation, which are regularly found in general life and which affect so many of those who are afflicted Avith tuberculosis prior to the time when the disease becomes manifest. We may say, however, that, as a rule, digestion becomes more impaired and stasis and constipation become more pronounced as the disease advances and toxemia and the various depressive emotional states become more marked. Thus it would seem that early tuberculosis is a condition in which increased vagus tone naturally predomi- nates over sympathetic stimulation; and advanced tuberculosis a condition in which sympathetic irritation seems to be greater than the vagus tonus. The degenerations which occur after the dis- ease has existed for a long time are accountable for many of the symptoms. In offering this analysis of nervous action in tuberculosis, I realize fully that it is impossible to always point out the direct relationship between cause and effect ; because we are dealing with a disease which produces dysfunction on the part of many organs and which results in a multitude of conditions which might pro- duce symptoms similar to those which could be explained at one time by irritation of the sympathetics, at another by irritation of the vagus. It can be seen, however, that these two systems are to be taken into account; and that, as long as inflammation in the lung exists, so long are impulses carried to various organs through these two systems, which, acting antagonistically, dis- turb the normal equilibrium, which is so necessary to normal function. CHAPTER VIII. THE NERVOUS SYSTEM CONTINUED: THE RELATION- SHIP OF THE SYMPATHETIC NERVOUS SYSTEM TO TOXEMIA AND THE DEPRESSIVE EMO- TIONAL STATES IN TUBERCULOSIS. The clinician must ever turn to physiology and pathological physiology for the explanation of phenomena which he observes in medicine. The study of medicine, however, increases greatly in interest as he is able to assign a plausible reason for observed facts. Volumes have been written in explanation of the phenom- ena of anaphylaxis. Temperature has been discussed in every text book dealing with diseases accompanied by toxic conditions. The symptoms which accompany toxic states are well known, and more or less accurately described, yet a fully satisfactory ex- planation of the rationale of their production has not been of- fered. Primarily I believe that it is justifiable to state that the symp- toms which accompany a disease are at least partly associated with the means which the organism provides for its defense against that disease. It may be difficult at times to see how this works out, especially when the symptoms become so serious as they often do when the organism succumbs to the disease. Our answer to this is that it is not the symptoms which cause death but the disease itself ; and that the disease may become so serious that the very means which have been developed for the defense of the organism may become abnormal and even harmful. To understand this better I would cite instances of physical defense in which the means of defense proved harmful. At the time of the Lusitania disaster the story is told of a woman and three men who seized hold of a piece of wood which was suf- ficient to help them all to keep afloat. Nature turned all the latent forces within their bodies to active working power and gave them almost superhuman strength of muscle to preserve 218 NERVOUS SYSTEM IN TUBERCULOSIS them from death ; but, in spite of this, one by one they let loose their hold; and all perished but one. The unnatural strength which was thus developed, and which would have saved everyone of them, had the struggle not been too long, ended in exhaus- tion, and permitted the enemy against which they were strug- gling, to overcome all but one ; and she was nervously and phys- ically exhausted for days, as a result of the struggle. Many instances are also cited in the present European war where men have been compelled to defend themselves by supreme effort. The retreat from the Mons to the Marne is a case in point. Phy- sical and nervous energy were developed in the troops who made that retreat to an extent that seems incredible. For nine days men marched, averaging twenty miles a day, harassed continu- ally by an enemy. They were enabled to do this because the necessity of self-preservation demanded it and the latent powers within them were called into action and every particle of force which the body could muster was converted into muscular energy to be utilized in making their escape. This supreme effort was fol- lowed by exhaustion. Many men fell by the wayside, and those who succeeded in making their escape were exhausted nervously and physically. Many of them sank into an unconsciousness, a sleep which lasted two or three days; some to waken no more. In both of these instances the exhaustion was a result of the overworking of the means of defense. The same is true in infectious diseases. The body is confronted by an enemy. Its defensive powers are called out, not for the supreme physical effort only, but for a chemical effort, requiring energy none the less. Bacteria liberate foreign protein molecules when they go into solution and during their growth. These molecules are set free in the tissues. As a result of chemical ac- tion they are destroyed, liberating toxic molecules. If these toxic molecules are set free in great numbers the organism may be un- able to stand their action and death may result. When infectious microorganisms enter the body, if implantation results, the meta- bolic processes of the body are increased. As a result of this in- creased metabolism, there is an increase in heat production. The toxic molecule, which results from splitting up the protein mole- cule, is set free and acts upon the cells of the central nervous NATURE OF DEFENCE AGAINST BACTERIA 219 system. It stimulates the vasomotor centers, and, through, its ac- tion upon the sympathetics, produces a constriction of the super- ficial vessels, interfering with the liberation of heat. As the com- bined result of the increased oxidation and decreased elimination, of heat, the body temperature rises. This increase in tempera- ture has a tendency to check further multiplication and growth of bacteria. Whether or not this is a part of the program of de- fense, it is difficult to say ; but an increase in temperature, particu- larly when it reaches a maximum of 100° or 101°, or more, cannot help exerting an inhibitory influence on the growth of bacteria. Whenever the bodily forces are called upon for defense, whether it be to attack an enemy, to escape from an enemy, or to fight an infection, the processes which go on within the body are the same in principle. Latent energy is transformed into active working energy; and, in order that the protective forces of the organism may be as great as possible where the danger is serious, the in- ternal viscera are called from duty for the time being, their func- tion being temporarily inhibited that the energy ordinarily used up by them may be devoted to defense. Crile 1 has shown that the particular organs which are con- cerned in defense are the brain, the adrenal gland, the thyroid gland, the liver, and the muscles. These, he speaks of as the "Kinetic system," a system which is "evolved primarily for the transformation of latent energy into motion and heat;" the motion and heat being the two forms of energy which are util- ized by the organism in defense. These organs are all more or less interdependent in their action. Cannon 2 has especially studied the action of the adrenal glands and shown how, ow- ing to the fact that it is innervated through the sympathetics (splanchnics) its action is dependent upon the same stimuli as those which affect the sympathetics in general. He has also shown that the effect of adrenin which results from this stimulation when thrown into the circulation acting peripherally upon the myoneural junction of the sympathetics is to further produce or prolong the same action as results from central sym- pathetic stimulation. Thus, adrenin in the blood causes dilata- 1 The Origin and Nature of the Emotions, W. B. Saunders Company, 1915; Man — An Adaptive Mechanism, The Macmillan Co., New York, 1916. 2 Bodily Changes in Pain, Hunger, Fear, and Rage, D. Appleton & Co., 1911. 220 NERVOUS SYSTEM IN TUBERCULOSIS tion of the pupil, rapid heart action, a checking of the gastro- intestinal secretions and motility, and a setting free of glycogen from the liver, phenomena, all of which represent sympathetic stimulation. The central nervous system is the constant recipient of im- pulses. These impulses, if sufficiently strong, call forth a re- sponse which results in action. Every conceivable agency act- ing upon the body, whether it be a toxin, a protein, pain, joy, sorrow, discontent, the pleasure of a beautiful landscape, or the horror of the battlefield, produces impressions upon the cen- tral nerve cells which, when sufficiently strong, produce action in accordance with the type of the stimulating agency. Impulses of lesser degree are received without causing action. One peculiar characteristic of stimulating agencies is their selective action upon peripheral nerves. One impulse may act through the somatic nerves, another through the sympathetic, and still an- other through the vagus. There are many instances in which the action is even more selective than this; where only one portion of the vagus, for example, or a single brain center, is stimulated. Knowing the selective action of the digestive juices, and the selective power of body cells to take from the blood stream the particular substances required for their growth and function, and to reject those which are valueless or harmful, and appreciat- ing the selective action of the substances secreted by the various glands of the body, we are prepared to believe that the purposes of the organism are best served by a nervous mechanism which is also selective in its reaction to harmful stimuli. We observe that certain stimuli in which we are led to believe that primary action is peripheral, act principally upon the nasal branches of the vagus, others upon the bronchial, others upon the cardiac, and still others upon the gastrointestinal branches. Other central stimuli act upon the sympathetic and still others upon either the sensory or motor nerves supplying the skeletal structures. It may be that this should be spoken of as a selectivity in re- sponse or reaction rather than in action; for, it may be that the impulses which meet the nerve cells affect all, but only produce response or reaction in definite groups. This latter sug- HARMFUL STIMULI INJURE NERVOUS CENTERS 221 gestion seems to hold for those groups of bodies which produce toxemia and anaphylaxis. The syndrome of toxemia is central stimulation plus the sympathetic syndrome of inhibited function on the part of the internal viscera; while the syndrome of anaphy- laxis is that of central stimulation plus the vagus syndrome prob- ably caused by peripheral irritation of the nerve endings of the particular branches of the vagus which show the irritation. The effect of toxemia, worry, fear, etc., is to produce reaction on the part of the body so that the effect of those actions may be neutralized. A long continued action of these harmful stimuli causes overwork and overstimulation, which leads to a degree of ex- haustion of the protective mechanism. This leads to neurasthenia, exhaustion or perversion of the action of the nervous system; psychasthenia, exhaustion or perversion of action of the higher or psychical centers; myasthenia, exhaustion or- perversion of action of the motor mechanism ; in fact, we might express this whole con- dition as a general cellular and psychical exhaustion or perversion of action. As a clinical picture we see this in all degrees of severity. We see it as an acute process in such conditions as acute toxemia and shock, and as a chronic process in such states as the protracted toxemias, and the prolonged nervous depressions. Perverted ac- tion on the part of the important organs of the body under such circumstances is known to us all. A study of the changes in the important organs as a result of these harmful stimuli has been made by Crile 3 and his associates by which they have been able to show the effect of harmful stimuli upon the brain, adrenals, thy- roid, and liver. Crile thus approaches the subject of the effect of harmful stimuli (among which are diseased conditions) "upon the body by studying the impression that these stimuli make upon the mechanism of defense. His work shows that changes in the brain, adrenals, thyroid, and liver follow either marked harm- ful stimulation of short duration, or less severe stimulation when prolonged. With these suggestions before us we are now prepared to study the syndrome of toxemia. We must look upon the symptoms which accompany toxemia as being a result of the attempt of s Man — An Adaptive Mechanism, Macmillan, New York, 1916. 222 NERVOUS SYSTEM IN TUBERCULOSIS the body to destroy the toxins, as well as a result of the action of the toxins themselves. - When bacteria, or any other foreign protein enters the cir- culation, it is split up into toxic and sensitizing molecules (Vaughan). The toxic molecules act upon the cells of the cen- tral nervous system and cause them to send out stimuli, particu- larly through the sympathetic system to the tissues supplied by it. The effect through the sympathetics is widespread. At some period during the toxic state, depending upon the degree of toxemia present, there is a stimulation of practically all the tissues and organs supplied by the sympathetic nervous system. This is noted in the epidermal tissues as: first, a stimulation of the pilomotor muscles, causing the condition of "goose flesh" which very often appears preceding or during the chilly sensa- tions which result from toxemia; and, second, in the stimula- tion of the muscles to the sweat glands, causing an increase of perspiration. There is also a stimulation of the vasomotor system, causing vasoconstriction. There is a stimulation of the sympathetic fibers exerting an inhibitory action upon the internal organs where activity is increased by the greater vagus nerve, as shown by the lessening of the gastrointestinal secretions, and by the reduction in the gastrointestinal motility. The same sympa- thetic stimulation is shown in the heart by the increase in pulse rate. Stimulation of the adrenal glands is shown by the in- crease of secretion of adrenin, which is accompanied by a forc- ing of glycogen from the cells of the liver. The effect of this stimulation is a general inhibition of func- tion upon all the tissues supplied by the vegetative nervous sys- tem. The purpose of the organism, for the time being, is de- fense; consequently, the functions of organs which are not im- mediately necessary for that purpose, are checked. The demand for energy required by the digestive system is temporarily re- moved and the needs of the body are supplied by other methods. This is particularly noted in the fact that the glycogen stored up in the liver is brought out into the circulation for consump- tion. The adrenal glands are stimulated, and they, in turn, stimulate the entire mechanism of defense, bringing the brain, ACTION OF TOXEMIA 223 the liver, and the thyroid gland into action in the transformation of latent energy into active defensive forces. As a result of this sympathetic action, there results a group of phenomena, which make up the syndrome of toxemia. This is the same, except in minor details, no matter from what source the toxemia comes. The syndrome varies according to the de- gree of toxemia present, and whether the inoculation of toxin is single or multiple. Among the most common symptoms be- longing to this syndrome are malaise, lack of endurance, nervous instability, loss of strength, rapid heart's action, lack of appetite, furred tongue, and hyposecretion and hypomotility throughout the gastrointestinal tract. It can be seen that this group is definitely the picture of central stimulation plus an expression of general discharge through the sympathetic system. While a temporary inhibition of function may be permitted, and the energy conserved may be utilized in defense, if long con- tinued, it appears to be deleterious; consequently, sympathetic stimulation should be relieved as much as possible that the vege- tative functions may go on undisturbed; for, while a temporary disturbance of these functions might be advantageous to the in- dividual, a prolonged disturbance produces injurious results. The sympathetics are irritated under several different cir- cumstances in tuberculosis, as follows : 1. Whenever tubercle bacilli are multiplying or going into solution, — whenever they are producing and liberating toxins. 2. Whenever, as a result of the process, tissues break down resulting in protein absorption. 3. Whenever other bacteria complicate the process and give off their toxins into the circulation. 4. When the patient becomes disappointed, discouraged and is dissatisfied with his condition and fears that he will not get well, when disturbed by business or domestic affairs; and when suffering from any of the depressive emotional states. From this it can be seen that toxemias and depressive emo- tional states as they occur in tuberculosis act centrally and at the same time cause general sympathetic stimulation ; and are produc- tive of inhibition of function of the various internal viscera, with an elevation of temperature and general loss of nervous and physi- 224 NERVOUS SYSTEM IN TUBERCULOSIS cal force. The picture of general neurasthenia manifests itself with its irritability of nerve centers and general loss of physiologi- cal balance whenever the process is long continued. Toxemia is an active force in tuberculosis whenever the tuber- culous process is active. It is most marked when the process is most acute. The system gradually grows accustomed to the presence of toxins and adjusts itself by the formation of a tol- erance or defense. When this state has been attained a consider- able amount of toxins may find its way into the circulation without producing marked symptoms. In fact, after the period of acute activity has passed, it is the rule for the so-called toxic symptoms to disappear. They can be brought on again, how- ever, by exertion. Exertion could act either by forcing more toxins out into the circulation as is generally stated (so-called autoinoculation) or by oxidizing the toxins more rapidly or as a result of the increased oxidization attendant upon the extra work produced. The tuberculous patient who rests quietly is free from the symptoms of toxemia as a rule, except during the periods of growth of bacilli and extension of the process to new tissue and during the time of active breaking down of tissue. Toxic symptoms are increased by exertion and diminished by rest; consequently rest is an important factor in treatment dur- ing the toxic state. The more persistent symptoms belonging to the toxic group are those which belong particularly to the central nervous system itself, those which are due to the partial exhaustion of the nerve cells; malaise, lack of endurance, loss of strength, and nervous instability. These persist much longer, as a rule, than the symp- toms on the part of the internal viscera such as rapidity of heart action, diminution of secretion and diminution of motility of the gastrointestinal tract. The organs of the body seem to have a wide range within which they can functionate fairly normally; and, they seem to be able to withstand considerable abuse and still carry on their part in the animal economy. The same syndrome is present during the depressive emotional states as during the states of toxemia, although the symptoms are, as a rule, milder in character. Thus, the patient who is in pain, also the one who is disappointed, fearful, anxious, dis- THE SYNDROME OF TOXEMIA 225 couraged, pessimistic and homesick, likewise the one who is dis- contented, cross, irritable and angry, suffers from a degree of nervons exhaustion and general inhibition of functions of the in- ternal viscera. These conditions depress the functions of the in- ternal viscera and lower the power of fighting the disease. There- fore, pain should be relieved if possible and the patient should be kept as cheerful and happy as possible. In a recent paper 4 I discussed the relationship of the group of symptoms which ac- companies toxic conditions to the sympathetic nervous system, and, while I made the discussion general, it applies to the subject under discussion. I quote the paper in full, although by doing so, a slight amount of repetition is unavoidable. "The human body under normal conditions has a perfect phys- iological balance. The relationship of one part or organ is in a state of perfect balance with every other part or organ. A disarrangement of this equilibrium produces pathological con- ditions and dysfunction. The derangements are indicated by symptoms and signs, which, when grouped, give us a picture of definite disease. "The explanation of well known symptoms is often wanting, the practitioner being compelled to learn them as a part of the symptom-complex, belonging to a certain disease instead of being able to point out the exact forces operating to produce them. An etiological classification of symptoms leads us to a better under- standing of the disease in question and facilitates diagnosis. "In analyzing the symptoms in early pulmonary tuberculosis, I found that they could all be classed etiologically in three groups : 1, those due to toxemia ; 2, those due to reflex action ; and, 3, those due to the tuberculosis process per se, as shown in the table on page 226. "In this manner we classify some twenty-six symptoms which belong to tuberculosis in three groups so that each symptom in the individual group is due to a common etiological factor. Such a classification simplifies diagnosis. It offers an explanation for the fact which has long been observed, — that symptoms are variable in that the same ones are not always present, and when present, they are not always prominent. 4 The Syndrome of Toxemia, an Expression of General Nervous Discharge Through the Sympathetic System, Journal American Medical Assn., Jan. 8, 1916, vol. Ixvi, pp. 84 and 85. 226 NERVOUS SYSTEM IN TUBERCULOSIS "When studying these three groups of symptoms I was im- pressed with the fact that there was nothing distinctive of tuber- culosis in that group which is due to toxemia. The same symptoms could be due, as well, to an infection of the tonsil, the prostate, the fallopian tube, a toxemia from intestinal stasis or an acute infectious disease. They are, in short, a part of the syndrome of infections in general. I was further impressed with the fact that the second group, those of reflex origin, all point to organs other than the lung, but that they belong to organs which are supplied by the vagus and sympathetic nervous system, both of which supply the lung. A further analysis of the group which is due to toxemia shows that these symptoms are identical in dis- Group I. Group II. Group III. TOXEMIA. REFLEX ACTION. TUBERCULOUS INVOLVE- Malaise Hoarseness MENT PER SE. Lack of endurance Tickling in larynx Frequent and protracted Loss of strength Cough colds Nervous instability Circulatory disturbances Spitting of blood Lack of appetite Digestive disturbances Pleurisy Digestive disturbances Loss of weight Sputum Loss of weight Chest and shoulder pains Temperature Eapid pulse Flushing of face Night sweats Apparent anemia Temperature Anemia* *Since writing this paper, I have been able to explain several other symptoms as be- longing to this group, such as headache and general aching; and, when the toxemia is very severe, producing collapse, there results: 1, vasodilatation (vasomotor paralysis); 2, sweat- ing; 3, subnormal temperature. tribution and effect with a general discharge of nervous impulses through the sympathetic nervous system. "To make this clearer it is necessary to recall that the auto- nomic nervous system supplies impulses to structures which are not controlled by the will. These are the organs supplied by smooth muscle such as the stomach, intestines, blood vessels, ducts of glands; also certain organs possessing striated muscle fibers such as the heart, the beginning and terminal portions of the alimentary canal, and the generative organs. "The autonomic system is divided into three groups; 1, the THE SYNDROME OP TOXEMIA 227 cranial and bulbar, which are spoken of as the vagus system; 2, the thoracic and upper lumbar, known as the sympathetic system; and 3, the lower lumbar and sacral, known as the sacral system. (In this paper I used the term autonomic to designate the entire vegetative system.) ''The vagus system is the system which conserves life. It con- tracts the pupil, increases salivary secretion, slows the heart beat, causes an increase of gastric and intestinal juices, and, furnishes motor power for the gastrointestinal tract. The sacral system controls the emptying of the lower bowel and bladder and presides over the generative functions. The sympathetic system sends branches to all organs supplied by the vagus and sacral systems; and where the fibers from these different systems meet there is an antagonistic action between the sympathetic and the other two systems. If the sympathetic stimulation is sufficiently strong, it overcomes the vagus and sacral tonus. If this control is only momentary or of short duration, as it is in fear and anger, as shown by Cannon 5 the general strength of the individ- ual is increased. He possesses for the time being, a power greater than normal. On the other hand, if this sympathetic control continues, a general inhibition of function in the organs supplied by the sympathetic system takes place and the in- dividual's powers suffer a diminution; thus, the dry mouth, lack of desire for food, stoppage of digestion, and rapid heart's action, which are temporary in the presence of the major emotions, are emphasized and prolonged during toxemia and are expressed as a general malaise, a more or less continuous absence of ap- petite, coated tongue, retarded digestion, constipation, rapid heart action and tendency to perspiration. "While impulses may be carried directly from the brain and cord to the skeletal muscles, insuring immediate and selective response and through the vagus and sacral systems through the intervention of a single ganglion, causing response limited to a certain organ; in the case of the sympathetic nervous system numerous ganglia are interposed and the response is shown in widely distributed parts. These ganglia act as modifiers or transformers of the impulse and make its distribution general, °Bodily Changes in Pain, Hunger, Fear, and Rage, D. Appleton & Co., 1915. 228 NERVOUS SYSTEM IN TUBERCULOSIS which accounts for the fact that so many organs and parts are involved in sympathetic irritation. "Whether a toxemia acts wholly centrally upon the sym- pathetic nervous system is open to some question. While the expression is that of general sympathetic discharge, yet we must bear in mind that it is possible that this may be partly due, or, at least, partly prolonged by certain internal secretions which are engendered by the same stimulation as that which produces the general sympathetic stimulation. Cannon has shown that the emotional states such as anger and fear, while being an expres- sion of general sympathetic discharge, may be kept up by adrenin in the blood. The adrenal glands are supplied through the splanchnics, and, impulses which cause a general sympathetic stimulation, stimulate these glands also. A minute amount of ad- renin poured into the blood stream has the effect of producing a prolongation of the condition which is brought about by direct sympathetic stimulation; thus adrenin will cause a dry mouth, impaired digestion, intestional stasis and a rapid heart. That toxemia, like the emotional states, acts by stimulating the sym- pathetics and by prolonging the action through the stimulation of the adrenals seems quite certain. It may also be found on further study that disturbances in other internal secretions may have a part in this general picture; but even should this prove true, it will not alter the fact that the syndrome of toxemia is an expres- sion of general sympathetic discharge." Further studies show me that the above paper does not em- phasize sufficiently strongly the fact that toxins and depressive emotional states act centrally, causing a general irritability of the central cells. The general expression of inhibition through the sympathetics, however, is well emphasized. Physiologists tell us that the action of adrenin upon the internal viscera is produced through peripheral stimulation instead of cen- tral stimulation of the sympathetics. The particular point in the reflex arc which is acted upon is the myoneural junction where the nerve endings and the muscle cells join. P. J. Meltzer and Clara Meltzer 6 proved that adrenin acts peripherally instead of centrally by studying its action upon the vasoconstrictors in a e The Share of the Central Vasomotor Innervation in the Vasoconstriction Caused by Intravenous Injection of Suprarenal Extract, American Journal of Physiology, vol. ix, p. 147. ADRENIN ACTS PERIPHERALLY 229 rabbit's ear. The vasoconstrictors to the rabbit's ear pass through the sympathetics from the superior cervical ganglion, and through the auricular magnus, a branch of the third cervical nerve. By cutting the third cervical nerve and removing the superior cervi- cal ganglion, connection with the central nervous system was de- stroyed. Regardless of this fact the intravenous injection of adrenin still produced a constriction of the vessels of the rabbit's ear, showing that the action must be peripheral instead of central. CHAPTEE IX. THE CIRCULATORY SYSTEM IN TUBERCULOSIS. A good heart is the best asset that a patient suffering from tuberculosis can have. It serves him well during the time when he is struggling with the disease as an infection capable of ar- restment; and it usually proves to be the determining factor as the disease progresses. The question of the displacements of the heart as they occur in advanced tuberculosis will be discussed fully in Chapter XI so it need not be repeated here. The heart begins to feel the effect of tuberculosis as soon as the disease is of sufficient magnitude to cause an appreciable diffusion of toxins into the tissues or to interfere with inspira- tion by producing changes in the elasticity of the pulmonary tissue or by reflexly disturbing the muscles of respiration, or reflexly influencing the heart itself through its nervous mech- anism. Nervous Influences upon the Heart in Tuberculosis. — It is im- possible to understand the symptoms on the part of the heart in tuberculosis unless we have a definite understanding of its nerve control and the factors which are present to influence this. In discussions upon the heart in its relationship to this dis- ease it is usually said that a rapid pulse is one of the early signs. It is also considered to be a factor throughout the entire disease. This statement, however, must be modified, as can be readily seen by observing tuberculous patients both at rest and during exertion, during the various phases of the disease. The pulse rate in tuberculosis is variable because the condi- tions which affect the nerves that innervate the heart are vari- able. In order to understand the influences which act in increasing and decreasing the rate of the heart beat it is necessary to bear in mind that the heart is supplied by both the sympathetic and vagus divisions of the vegetative nervous system. The sympa- thetic has a tendency to accelerate and the vagus to slow the NERVE CONTROL OF HEART 231 heart action. Toxemia acts by stimulating the sympathetic nerv- ous system centrally, consequently toxemia manifests itself on the part of the heart by increased rapidity of contraction. As a result of pulmonary tuberculosis we must bear in mind also that the nerve endings of both the sympathetic and vagus sys- tems are irritated by the inflammation in the lung and that these show reflex action in the heart and other visceral and somatic structures. On the part of the heart, reflex stimulation of the sympathetic tends to increase the rapidity of contraction, while stimulation of the vagus tends to decrease it; consequently, we have the heart subject to central stimulation of the sympathetic by the toxins, and peripheral stimulation of both the sympathetic and vagus by the inflammation in the lung. As a result of this action, as a rule, the vagus tonus is overcome for the time and the heart shows increased rapidity. When the toxemia has passed over, however, the central stimulation of the sympathetic ceases. Then the heart is subject only to the reflexes through the sym- pathetic and the vagus from the inflammation in the lung. It must be understood that I am now speaking only of direct nerye influence. There are many other factors which come in and will be discussed in the proper place. In many patients the vagus and sympathetic stimulation bal- ance each other, the normal equilibrium is maintained, and the normal number of heart contractions result. In other cases the vagus predominates over the sympathetic and we find the pulse even slower than normal. In still others, however, the sym- pathetic action is the stronger and the pulse remains rapid. It has long been said that a persistently rapid pulse in tuber- culosis means a bad prognosis. While this is not invariably true, there is some ground for it because it means that the pa- tient's sympathetic tonus is in the ascendency; and this, being the inhibitory system, causes a diminution in the gastrointestinal functions and in the functions of all the other important viscera of the body. It would be more rational to state that those pa- tients who are distinctly of the sympathetic tonus type, or those people who have a decreased vagus tonus, which means practically the same thing, are not as able to withstand the disease as those who have increased vagus tonus. Charts shown in Chapter VII, Figs. 29-36 inclusive, illustrate the peculiarities of the pulse here de- 232 CIRCULATORY SYSTEM IN TUBERCULOSIS scribed. The particular characteristics of the pulse in early- tuberculosis, which are dependent upon disturbances in the heart's nervous mechanism, are: first, rapidity during periods of tox- emia ; second, either a normal, an increased or a decreased rapid- ity during periods of quiescence, while the patient is at rest; third, instability of the pulse on exertion; its reaching a higher point and returning to the normal slower than usual, being a very common condition. (Figs. 29-36, pages 200-213.) After acute toxemia has passed over, toxic symptoms may con- tinue through faulty methods of living and continue to show in acceleration of the pulse rate. Such emotions as disappointment, fear, anxiety, discouragement, as described in Chapter VIII, have the effect of producing and prolonging the same symptom-com- plex as that produced by toxemia, though, as a rule, the symp- toms are not severe. Consequently, if the patient is discouraged and disappointed these conditions stimulate the sympathetic ner- vous system and produce rapid heart action. The accompanying chart (Fig. 37) illustrates this well. This patient was on duty as a nurse in the hospital. She was suffering from tuberculosis and was impressed with the fact that it meant death. After examination I gave her hope and told her that she could get well, and firmly impressed her with the idea that she would be re- stored to health. She continued her work just the same, but the effect of relieving her of fear and its depressing action upon the sympathetic nervous system is well shown in the appended chart. The influence of the nervous system upon the blood vessels can be well understood by the fact that the sympathetics sup- ply the muscular coats of the blood vessels of not only the in- ternal viscera, but of the skeleton as well with contractor fibers. Consequently, anything that disturbs the sympathetic nervous system is apt to find expression in the changes in vascular tone. There are other changes to be considered in the production of unstable heart action. It is impossible to determine how much of the effect is produced by one cause and how much by another. The problems become more and more intricate as the disease ad- vances and increases in complexity. At first, the general tis- sues of the body are disturbed little, if any. At this time the heart muscle is sound, unless injured by other factors. What- SYMPATHETIC STIMULATION RELIEVED BY HOPE 233 ■£ >» >> CTd J2 ^ u. o ^J ■pis* oi <« o' rt 2 3 JS .3 J 3 13 ■S <0 rt 3 P C u > >-. rt'O.d ri o a *i 2; +j o<* E " DO «42 ° s 2 4-1 g ° ? « 13 ^-o^ "5 3 u 52 S CL-M g«g O k, tn O O 2 13 "+* u o. I 1 " Si « B , S-a B c en £ g C * u D.-S 2 £ 2 « rj l) s.2 g-a OJ o a 0J > as .« .»-l 3-5^ 0> T3 3 n > • 'E.i' 5 ' „, rt u £ £ ,„ . b fig*gS 3 ft § 3 ta M rl-9 a i; bo •-> Vim _ Si "S*S «-2 '"C ba in ,S3 rt ^ ° g-3 a 3 ► * u v v pQ 3 O 4J 4-» 234 CIRCULATORY SYSTEM IN TUBERCULOSIS ever changes are present, as a result of the tuberculous process, are due to the central stimulation of the sympathetics by the toxins; the peripheral stimulation of both the sympathetic and vagus systems by the inflammation in the lung; and to the dis- turbance of the inspiratory act, interfering with its accessory aid to the circulation. Later, however, these causes are exag- gerated and to them are added the factors of malnutrition and general wasting; general degenerative changes as well as those affecting the heart muscle and blood vessels; displacement of the heart; disturbances in internal secretions; and the destruction and other changes in the pulmonary tissue. Physiological Facts. — To understand fully the effect of these deleterious factors on the heart and circulation we must have accurate physiological conceptions. The circulation of the blood is for the purpose of adding oxygen and combustible materials to the tissues and removing waste. This interchange takes place in the capillaries. It is necessary that the flow of blood through the capillaries be rapid that this exchange may be carried on properly. It is further necessary that the blood be conveyed to them with adequate force and be carried away with proper dis- patch. The blood pressure of the systemic arteries depends upon the amount of blood delivered in systole and the tension in the systemic vessels. It will be understood from the discussion in this chapter that the output at each systole is decreased and that the muscular tone of both heart and vessels is altered, particu- larly in the advanced disease. The lesser circulation varies somewhat from the systemic. The blood pressure here depends on the same factors as in the greater circulation, but the tissues are so different in texture, and the conditions so different, that the pressure is much less. The loose spongy pulmonary tissue offers little support in comparison with that offered by the solid organs and firm skeletal muscles. So does the negative intrathoracic pressure offer a reduced re- sistance to the vessels within the thoracic cage as compared with the pressure in other parts of the body. Both the systemic and pulmonary vessels are capable of enor- mous distention. Experiments have been made which show the surprising fact that large areas may be cut out of the systemic and pulmonary circulations without apparently producing any PHYSIOLOGICAL FACTS AND PATHOLOGICAL INFLUENCES 235 serious consequences in the circulation. Three-fourths of the pulmonary circulation has been cut off in dogs 1 without reduc- ing the amount of blood delivered to the left ventricle ; while the left lung has been tied off in the rabbit without causing a fall in the systemic pressure (Tigerstedt). Tigerstedt suggests that one-half of the pulmonary area may be cut off without any ap- preciable fall in the systemic blood pressure and suggests as the probable explanation that the vessels of the lung are probably never uniformly filled with blood, there being large areas of the lung relatively empty which are only properly filled when large portions of the pulmonary area are cut out of the circula- tion. The resistance of the lung is normally small and the blood pressure low. Effect of Pathological Reduction in Pulmonary Areas. — While experiments such as those mentioned above show the wonderful powers of adjustment in the pulmonary circulation, they must not be interpreted as meaning that- a large portion of the lung can be cut out of the circulation with impunity. If the same amount . of blood is forced through one-half of the pulmonary area in a given time as should be normally forced through the total area, it can only be done by an enlargement of the vessels and an increase in the power of the right ventricle. That such a condition would be followed by a diminished oxygenation of the blood and in that way eventually prove harmful to the entire organism and result in lessened tissue tone, is to be inferred. This is the condition that we find in advanced tuberculosis. As the disease progresses one area after another is involved in fibrosis and necrosis, and the necessary accompanying condition, — compensatory emphysema — until finally a large portion of one or both lungs is destroyed and the circulation is greatly em- barrassed. Under such conditions the systemic blood pressure is not maintained. It becomes progressively lower, regardless of hypertrophy of the right heart and rapidity of the pulse. Blood Pressure in Tuberculosis. — Blood pressure is lowered early in the disease, although wide departures from the normal are rarely seen except in advanced cases. This shows that the lowering of the systemic pressure is not primarily due to an in- ability of the right heart to propel the proper amount of blood 1 Lichtheim: Die Storungen des Lungen Kreislaufes, Berlin, 1876. 236 CIRCULATORY SYSTEM IN TUBERCULOSIS through the lungs into the left heart, thus into the general cir- culation on account of lack of muscular force; although this condition is often finally attained. Pike 2 says: "It is my belief that there are at least four mechanisms involved in the maintenance of blood pressure; namely, (1) the vasomotor nerves, whose common point or origin lies in the medulla oblongata; (2) the heart and its nerves — in- trinsic, perhaps, as well as extrinsic; (3) the skeletal muscles; and (4) some property of the tissues of the vessel walls, possibly in- dependent of the nervous system, in addition to those properties directly under control." From the above quotation it is evident that at least three, probably all of the mechanisms which maintain blood pressure, are disturbed in pulmonary tuberculosis. It is generally stated that toxins reduce blood pressure. This is untrue of toxins per se unless the toxemia be very severe. Toxins act upon the vasomotor center and through the sympa- thetic nervous system and produce vasoconstriction. This is one of the causes of rise in temperature which I have discussed in Chapter XXX, Vol. II. The state of toxemia, however, after it has existed for a prolonged time, produces other conditions which have a tendency to lower blood pressure. In early tuberculosis, lowering of the blood pressure is most probably due more to the lessening of the inspiratory act than any other single factor. In advanced tuberculosis many other factors enter, such as de- generation of the heart and wasting of the skeletal muscles. The effect of tuberculosis upon the heart is many-sided. In early tuberculosis we have not only the effect of the toxins act- ing centrally through the sympathetics, accelerating its action, but also a peripheral stimulation of both sympathetic and vagus fibers by the inflammation in the lung, the effect of the former being to accelerate, and the latter to slow the heart's action; consequently, through the entire course of pulmonary tubercu- losis there is a disturbed innervation, varying greatly according to the extent of the lesion and the degree of activity. Later, changes take place in the heart muscle itself ; first, that of hyper- trophy of the right ventricle in order to overcome the extra work thrown upon it by the disease blocking off the vessels in the 2 Nature of Surgical Shock, American Journal of Surgery, October, 1914. BLOOD PRESSURE IN TUBERCULOSIS 237 lung ; but, later, degeneration of the heart muscle, resulting from toxemia and general malnutrition. The skeletal muscles, while not particularly disturbed at first, sooner or later lose their tone, partaking of the general wasting of the tissues throughout the body. The loss of support to the vessels arising from decreased tissue tone must, of necessity, greatly interfere with their ability to maintain their normal tone, and it would not be at all beyond reason to suspect that vessel walls are weakened, the same as all other tissues of the body. There is no doubt that blood pressure, lower than normal, must exert an unfavorable influence upon the patient. In or- der to maintain proper conditions for metabolism to go on, a certain normal pressure in the circulation is demanded. In tu- berculosis, to the extent that this normal is reduced, there must be interference with nutrition. The effect of the various factors operating to alter pressure is to cause a wide departure from the normal in the blood content of various groups of vessels. The blood remains stored up in the venous reservoirs of the body, particularly in the liver and splanchnics, while the arteries are relatively empty. The effect of low pressure may be inferred from the follow- ing quotation from Pike: 3 "Whatever the immediate cause of the low blood pressures may be, it may well become part of a vicious circle. Even though the blood be well oxygenated by artificial respiration, and the heart be beating regularly, a pre- viously damaged portion of the central nervous system: e. g., the brain, after subjection to anemia, does not recover as long as the systemic blood pressure remains low. Nor does this fact need surprise us when we remember that, among the other rela- tively constant conditions of the mammalian body, a blood pres- sure varying but a few millimeters under the various conditions of activity from day to day or year to year is an important item. Any considerable variation from this usual level is strong presumptive evidence of abnormal processes involving other mechanisms than that of circulation." The failure of the heart to meet the requirements of exercise, particularly sudden strain in advanced tuberculosis, can easily be explained. The extra amount of blood required for the mus- 8 Nature of Surgical Shock, American Journal of Surgery, October, 1914. 238 CIRCULATORY SYSTEM IN TUBERCULOSIS cles during exercise is derived from the splanchnic area and ow- ing to the lessened inspiratory act, the conditions are such that it cannot be readily delivered to the right heart. Blood pressure is low in all stages of tuberculosis, although the readings of different observers show no uniformity on ac- count of individual variability. The degree of fall in pressure is modified by many factors, but is progressive as the disease ad- vances. My findings in blood pressure are well represented by the statistics of 162 patients examined and compared with 20 non-tuberculous individuals. 4 The readings were made by the Stanton sphygmomanometer. Sys. Dias. Hg. Sys. Dias. 20 non-tuberculous individuals 120 108 mm, 11 patients in I Stage 106 78 21 patients in II Stage 108 81 .30 patients in III Stage 103 75 While in this table the pressure in Stage II was higher than that of Stage I, this is purely accidental. Had the number of patients been larger the pressure in Stage I would have un- doubtedly been somewhere between the reading of 106 and that of 120 noted for the non-tuberculous. The only fact which I wish to illustrate is that the pressure is lower than normal and that it progresses with the disease. It is not uncommon in far advanced cases to find instances where the pressure falls to 90 mm. Hg. and at times below this. Extremely low pressure is associated with a very low tissue tone. Patients having very low pressure feel relaxed. They lack endurance, are easily fatigued, sometimes on the slightest exer- tion, even though not out of bed. On motion they often feel dizzy and faint. Poor appetite and digestion are often accom- paniments. "We meet this when there has been an extensive de- structive process in the lung, associated with marked interfer- ence with the inspiratory action of the thorax, and consequently a marked splanchnic congestion, a high grade of toxemia and a general wasting. When we recall that 82 mm. Hg. pressure is the point of syncope we can see that the low pressures of ad- vanced tuberculosis are approaching it and are inconsistent with feelings of well-being. 4 The Effect of Tuberculosis on the Heart, Archives of Internal Medicine, October, 1909. SMALL HEART AND ARTERIES 239 These low pressures are benefited by such lines of treatment as abdominal massage; treatment which will produce a deposit of fat in the abdomen; adhesive straps or belts which increase the intra-abdominal pressure and aid in forcing the blood from the splanchnic areas toward the heart; also by such remedies as have a direct tendency to raise blood pressure such as digitalis, citrate of caffeine and suprarenal extract. In the use of digitalis, larger doses should be employed than usually given. I not in- frequently given fifteen minims or more of a standardized tinc- ture three times a day for two days, then drop to ten minims for a period of four or five days; I then omit the remedy for two or three days and resume the same as before, keeping up its use over a considerable time. It has been noticed that a rise in blood pressure and clinical improvement go hand and hand. Some observers have attributed the improvement in the pulmonary condition to the increase of blood pressure. This is a factor in, the increased well-being of the advanced case as just mentioned, but it cannot be considered as standing in a causative relationship to the cure and arrest- ment of the tuberculous process. In early tuberculosis when the infiltrations in the lung disappear, nerve tone improves and the normal inspiratory excursion is restored wholly or almost wholly, the blood pressure rises and attains or approaches the normal. The rise in pressure stands as a result, not as a cause of the pulmonary improvement. In the advanced stage the in- creased pressure is due to increased nerve stability, improved in- spiratory action, improved nutrition, and better heart action. It cannot be denied, however, that the increased pressure reacts and further increases the patient's feelings of well-being and in that way furthers his improvement. Small Heart and Arteries. — In Chapter XI, page 301, 1 discussed the question of the small heart and suggested elsewhere 5 that it is probably the result of an embarrassed inspiratory act through which the heart is required to accustom itself to a de- creased blood content, likewise a decreased output. Benecke, B The Small Heart in Tuberculosis: A Suggested Physiologic Explanation, Journal American Medical Association, April 17, 1915. 240 CIRCULATORY SYSTEM IN TUBERCULOSIS as well as other pathologists, has shown that the same conditions obtain in the arteries, the arteries being narrower than normal. It can be seen how this cause would operate to produce narrow- ing of the arteries, as well as a reduction in the size of the heart. That the malnutrition of the late stages leads to an atrophy of the heart muscle is well established; but this is entirely apart from the small heart which has been spoken of by clinicians and which is found in early tuberculosis. Bohland 6 in discussing this question, states that Reuter 7 and Hirsch 8 and Kersten 9 proved the presence of the small heart by orthodiagraphic examination. He says: "Both found in the majority of tuberculous subjects (62.5-88 per cent) hearts which were too small; in fact, Kersten found hearts below normal in size in 62.5 per cent of well nour- ished patients." Not only were Kersten 's patients well nour- ished; but a large number of them were in the first stage of tuberculosis. Hypertrophy of Right Ventricle. — Tuberculosis presents sev- eral conditions tending to disturb circulation. On the part of the pulmonary circulation we have the obstructions in the ves- sels supplying areas of lung tissue of greater or lesser extent, either by the infiltration and collateral inflammation, or the destruction of lung tissue. We also have the embarrassment due to the encroachment upon the vessels which results from compensatory emphysema. It is evident from these conditions that, at least for a long time the circulatory burden in tuberculosis is upon the right heart. There is an obstruction of a permanent character to the circulation in the pulmonary vessels. This calls for permanent extra work upon the right heart. In order to measure up to the demand the muscle hypertrophies. The right heart bears the brunt of the disease and ultimately is the deciding factor be- tween life and death. Thickening of Arteries in Tuberculosis. — Examination of the arteries in chronic tuberculosis shows them to be thickened. 10 6 Handbuch der Tuberkulose, Brauer, Schroder und Blumenfeld, Johann Ambrosius Barth, Leipzig, 1915. 7 Dissert. Miinchen, 1884. s Deutsches Archiv fur klinische medicin, Bd. c. 8 Deutsche medizinische Wochenschift, 1911. 10 Pottenger: The Effect of Tuberculosis Upon the Heart, Archives of Internal Medi- cine, October, 1909. BLOOD VESSELS IN TUBERCULOSIS 241 The analysis of 162 patients examined with reference to the condition of the arteries showed the following result: Duration of Illness from First Definite Clinical Signs CONDITION OF RADIALS LESS THAN 1 TEAR 1 TO 2 YEARS MORE THAN 2 YEARS Palpable Non-palpable 14 14 20 21 60 33 These results were based on the examination of the radial artery, and were obtained after stripping the radial from below upward with the second finger of one hand and above downward with the second finger of the other hand, and then feeling the radials, emptied of blood, with the forefinger. Unless the pre- caution of stripping the vessel of blood is taken, the result will be unsatisfactory. Later examinations confirm these earlier observations. The cause of the thickened arteries is most probably in some way related to the toxemia. Support for this theory is seen in the effect of other toxemias in producing the same condition, and the fact that this condition is more common in chronic cases where the causative factors have had a longer time to act. Tuberculous Lesions of the Blood Vessels. — Tuberculosis may affect the blood vessels either from within or from without, and the lesion may be of all degrees of severity from that of very slight trauma to necrosis. Sometimes the infection is followed by an opening in the vessel wall and hemorrhage; sometimes an infiltration results which goes on to repair ; and sometimes an endarteritis with obliteration of the lumen occurs. It seems probable that many of the hemorrhages which we have in tu- berculosis, particularly those where only small amounts of blood are expectorated, may be due to the injury of vessels resulting from the action of toxins. 11 Bacilli invade the endothelial cells, give off toxins which at- tract leucocytes and thus form tubercles in the walls of the vessels. Miliary tuberculosis is a tuberculosis disseminated by way of the blood vessels in which many bacilli have escaped "Pottenger: Some Observations on the Classification and Treatment of Hemoptysis, American Journal of Medical Sciences, June, 1914. 242 CIRCULATORY SYSTEM IN TUBERCULOSIS into the blood stream and found lodgment in small vessels. It is from just such lesions as those here described that the bacilli which produce acute miliary tuberculosis come. The capillaries are most commonly affected, while small veins and arteries are less commonly so. Tubercles may be found in the walls of any of the vessels of the body, including the aorta. This being true, it is surprising that miliary tuberculosis is not a more common infection than it is. That it is not, is probably due to the fact that the vessel is often occluded by the inflammatory process so that bacilli do not get into the blood stream, and second that protective cell sensitization and antibodies reduce the virulence of or destroy the bacilli which gain entrance to the blood stream before they find lodgment in the tissues, in those patients in whom infection has been present long enough to build up a spe- cific immunity. Difficulties in Examining Hearts in Tuberculosis. — The exami- nation of the heart in advanced pulmonary tuberculosis offers many difficulties. The landmarks which have been learned in normal chests no longer hold because the heart is no longer sur- rounded by normal tissues ; and, itself, is often displaced. One does not always find, I might say in chronic advanced tuberculosis he rarely finds, the point of greatest intensity for the pulmonary valve at the second interspace to the left of the sternum, or the aortic valve at the second interspace to the right of the sternum, or the mitral at the apex which is usually found in the fifth interspace somewhat internal to the mammary line. In the shiftings of position which the heart undergoes as one portion of the pulmonary tissue wastes and contracts and other portions enlarge, the site for the auscultation of these valves shifts also. In order to be able to examine the valves it is essential to first outline the heart as a whole. The outlining of the area of absolute heart dullness is of comparatively little value in advanced tuberculosis. The information desired can be obtained only by knowing the accurate outlines of the organ as it lies in the chest. It must be remembered that it is the most movable portion of the mediastinum and as such may be shifted to the right or the left as is demanded by the intrathoracic com- pensation. DIFFICULTIES IN EXAMINING HEART 243 The points of greatest intensity for auscultating the pulmon- ary and aortic valves may both be on the left of the sternum in marked left displacement or on the right of the sternum in marked right displacement, or in any position between these two, as shown in Figs. 41 and 42, Chapter XI. The visible pulsation on the chest wall must not be taken for the apex. Quite often it is produced by the hypertrophied right ventricle as mentioned above and careful observation will show that the intercostal space draws inward as the ventricle con- tracts, instead of being thrust outward as it would be if the im- pulse were caused by the apex. Under such circumstances the apex will be found a considerable distance to the left of the point of pulsation. The inferior border of the heart is also at times lower than normal. Especially is this true in long-chested, enteroptotic in- dividuals, also in those who have forced the diaphragm down by emphysema and at times when tuberculosis develops in individ- uals who are getting along in years, or who, because of their dis- ease, age prematurely. Suspensio cordis is not uncommon in such cases. It is important to bear in mind that the valve sounds are great- ly influenced by their surroundings, consequently they cannot be compared as they can be in individuals who have no change in the pulmonary tissue. While the valves at the base of the heart are usually covered, when contraction of the pulmonary tissue occurs at one apex and this is followed by enlargement and com- pensatory emphysema of the other lung, one valve may be di- rectly against the chest wall while the other has an additional thickness of pulmonary tissue between it and the chest wall. Listening to these two valves under such circumstances with ref- erence to comparing their intensity, can give none but erroneous information. Consolidation of lung tissue, emphysema and cavities affecting the tissues adjacent to the valves also affect the character of the tones. Organic Heart Lesions and Tuberculosis. — If we accept the idea that clinical tuberculosis is an accident which may happen to any member of the human family, we will not be far from the 244 CIRCULATORY SYSTEM IN TUBERCULOSIS truth; and, further, we will be ready to look for about the same general complications that we would expect in the same num- ber of non-tuberculous individuals, unless there be some specific reason why such complications militate against tuberculosis. It is quite generally accepted that all such organic heart lesions as from their nature produce hyperemia of the pulmonary tis- sue, are antagonistic to the development of pulmonary tubercu- losis. This does not, however, preclude the possibility of such infection taking place, or the possibility of such an infection developing into active clinical disease when the infection has oc- curred; for all such protective conditions must be looked upon as being more or less relative. I have met with a number of instances of such heart lesions in tuberculosis and my experience with them has been unfavor- able ; so, while they may render a relative resistance to the bacil- lus, yet I cannot feel that the hyperemia produced is a factor which can be at all compared with the aid in arrestment which comes from a normal heart. Heart Bruits. — The heart tones in tuberculosis are often im- pure. Sometimes a distinct bruit is present which partially or wholly displaces the heart tone. Sometimes it is heard best on ordinary inspiration, sometimes it is eliminated by forced in- spiration. The character of these bruits varies, but for the most part they are soft. They cannot be positively separated from organic heart bruits. In fact, some writers believe that all bruits which take their origin from the valves are produced by some abnormal vibration of the valves or the adjacent vessel walls. Aside from the bruits which cannot be separated from the heart valves there are others which are unmistakably caused by pleuropericardial adhesions and others due to kinking and encroaching upon the lumen of the vessels by the pathological changes present. Degeneration of Heart Muscle. — The hypertrophied heart is able to meet the demands of the circulation at first; but, as the changes in the lung become more widespread, a time comes when any extra exertion is met with difficulty and cardiac weakness of a greater or lesser degree manifests itself. This is the greater when the disease is not only widespread but active; for, during DEGENERATION OF HEART MUSCLE 245 this time malnutrition is increasing and poisons are being poured out into the tissues, both of which cause degeneration of the heart muscle along with other tissues. Strangely, the heart in tuberculosis has not received as much consideration as it deserves. This has been due to our narrow view of tuberculosis, looking upon it as a disease of the lungs, when, in reality, it is an infection of the pulmonary tissue from which, at least in the advanced stages, every organ and cell of the body is injured. The heart comes in for an unusual amount of disturbance, both in its texture and function. I have spoken of the small heart which is found in tubercu- losis, even in the early stages and have given a physiological ex- planation for it. There is also an atrophy of the heart in tuber- culosis which occurs as a late manifestation being a part of the general malnutrition and muscle wasting. The result of prolonged toxemia in tuberculosis finally shows upon the heart muscle. As Satterthwaite 12 says: "We can now say that all toxemias, acute or chronic, cause dyscrasias and hy- peremias if long continued or severe, and other conditions to be mentioned later, produce definite morbid changes in the heart walls, evanescent or permanent, as the case may be. ' ' This fact calls for special attention to the heart in dealing with this dis- ease. All things else being equal, the patient with the good and well cared for heart has a decided advantage in his struggle for overcoming tuberculosis and particularly advanced tuberculosis. The subject of valvular lesions is of comparative insignificance to the condition of the myocardium itself in tuberculosis ; for the majority of deaths in this disease are due to an exhausted heart muscle. The changes in the muscle substance are not as evident in a slow going toxemia like tuberculosis as they are in a disease in which the toxemia is of a very high grade such as diphtheria ; yet, they are no less a factor in determining the outcome of the disease. The changes in the muscle substance in tuberculosis are general, as a rule; and the ultimate effect, no less than in acute toxemia, is to interfere with the contractility of the muscle, reducing the heart power. Unfortunately, in advanced tuberculosis, there is no way of "Cardio- Vascular Diseases, New York, 1912. 246 CIRCULATORY SYSTEM IN TUBERCULOSIS JS^S^I^isissSftisi? TrTm"' II 1 1 "TWIT 1 1' 1 1 -I 1 ' 1 1 1 - 1 } [|| 1} J. 1 j|i I || i j }i i J i 'il 4 - 1 ill 1 []]]]]] 1 |i 1 |j fM r 5 ! )^ u. >. ! ! 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Whatever embarrassment exists as a result of blocking off and obstructing the flow in the blood vessels of the lung is perma- nent; so, the only way of affording relief is through increasing the strength of the heart itself, and guarding it against all un- necessary strain. Clinical Evidence of Failing Heart. — The symptoms which first appear when the heart begins to weaken under the strain in tu- berculosis are rather vague and easily go unrecognized. It is much easier to look back and ascribe to them their proper significance than it is to recognize them at the time. The symp- toms which I have noted most commonly are, nervousness, anx- iety, insomnia, lagging appetite, and at times, poor digestion. These symptoms can be caused by so many conditions that un- less one has the heart in mind the true cause will most likely be overlooked. The pulse at the same time becomes soft and weak and the heart tones become weak on auscultation. But this latter char- acteristic is not always readily discovered, because the sounds may have been weak previously. These symptoms are often present before any marked dilatation can be determined; this, with precordial pain usually being a later manifestation. Some increase of the pulse rate usually accompanies the early signs of weakened heart, but not the progressively rapid pulse noted at the time of acute dilatation. On examination an enlargement of the heart from left to right is made out on palpation and percussion. Pigs. 38 and 39 show the way in which the pulse and tem- perature curve separate in terminal dilatation of the heart. As the heart becomes more and more unable to do its work it con- tracts less forcibly and more rapidly, the body becomes less and less able to react and so the temperature falls lower and lower 1 until death results. See pages 246 and 247. Myocardial weakness, as it affects the right heart, produces a very different picture from weakening of the left heart. Dyspnea is not a very prominent symptom when the right heart is at fault, except when the heart is called upon to measure up to an extra exertion. It is a marked symptom of weakness of the TREATMENT OF FAILING HEART 249 left heart, however, even when the patient is at rest. Stasis, in the systemic veins, however, is regularly present in weak- ness of the right heart, but not regularly present in weakness of the left. Pulse disturbances are present in both. When dyspnea and venous stasis are both present, together with pulse disturbances, it is evidence of weakness of the entire heart. Death from tuberculosis, being usually a right heart death is peaceful and painless. Treatment of Failing Heart. — Not being able to relieve the load on the right ventricle we can only strengthen it and make as little demand upon it as possible. In order to accomplish the latter, rest in bed should be enforced. It will be recalled that the amount of oxygen made necessary by arising from the recumbent to the erect position is doubled and the amount to start going is quadrupled. This can only be furnished by the heart increasing its output of blood in a given time. Con- sequently, rest in the recumbent position is one of the most valuable aids to such a heart, for it relieves it of all remov- able load. For the heart muscle itself I have great confidence in the use of digitalis and citrate of caffeine. If the early symptoms mentioned above are recognized and the patient is put in the recumbent position and given digitalis in proper doses, the crisis can often be averted. Digitalis strengthens the heart's con- tractions and in this way probably affords better nutrition to the organ; but, whether this is the explanation or not, I have great confidence in its use. If digitalis is to be used, it should be used in doses sufficiently large to produce an ef- fect. I use a standardized tincture in doses of x to xx minims three times a day until the pulse improves or the physiological effect is reached. This is generally shown by a nausea or ir- regularity of the heart. I then discontinue the remedy for three days and then repeat again, giving the remedy three or four days and then withholding it for a like period. Citrate of caffeine can be given in in grain doses every four hours and continued as long as necessary. The patient should be fed nourishing food in concentrated form. The bowels should be kept free to relieve any toxins 250 CIRCULATORY SYSTEM IN TUBERCULOSIS that can be removed through the alimentary canal. The im- portant thing in the handling of these cases is to recognize them early, and to treat them properly. These degenerative changes in the heart muscle may threaten the patient's life and yet the heart may recover itself as the patient improves. CHAPTER X. THE DIGESTIVE SYSTEM IN TUBERCULOSIS. General Observations on Nutrition. — How different our con- ception of nutrition and its problems since we have come to learn that digestion is more than the dissolving of food by salivary, gastric, and intestinal ferments. Substances of all kinds enter the stomach as food, substances which, if ab- sorbed in the state in which they are ingested would completely disorganize the entire cellular system. The function of the gastrointestinal juices is to break down the many compound substances which are eaten as food and to reduce them to sim- ple substances which the body can utilize. In the form in which they are ingested many of them are not foods, although they contain substances which may be converted into foods and utilized in building up cells and furnishing energy for running the human machine. The protective action of the gastrointestinal ferments is a very important part of its digestive function. Our admiration for nature's protective program for man is greatly increased by our better understanding the protective plan of the diges- tive tube. The heterogeneous masses which are ingested are broken down and split up into substances which the organism can utilize and those which it cannot. The latter, if absorbed, would be harmful. The former, in order to be properly utilized must be carried to certain structures to be further elaborated. The cells of the mucous membranes of the digestive tube are en- dowed with such defensive powers, we almost feel like saying selective intelligence, that they pick up those particles that the body cells can utilize and refuse to take those which it cannot use. Not only this, but different cells pick up differ- ent substances; thus the fats are absorbed and carried through the lymphatics to the blood, while the substances derived from 252 DIGESTIVE SYSTEM IN TUBERCULOSIS carbohydrates are taken up by the blood and carried to the liver. Should any substance which is not in harmony with the tissues gain entrance to them, the cells with which they come in contact outside of the digestive tract, form defensive ferments and split them up into substances which may be utilized as food and other substances which cannot. These latter are then acted upon further and further until they are rendered harmless, if that be possible; or, if not, until they are excreted from the body, or gain mastery over it. Abderhalden's discussion of the defensive ferments produced by the cells clarifies some of the problems of human existence and sheds light upon questions of maintaining the body cells in a state of equilibrium. 1 Nutrition in Tuberculosis. — The question of nutrition in the tuberculous, the same as in the healthy, comes far from being wholly a question of what or how much a patient eats, but has to do with the entire question of metabolism. Faulty nutri- tion may be due among other things to pathological conditions in the gastrointestinal tract, such as disturbances in secretion, or motility, or any acute inflammatory disease affecting the canal; errors in diet consisting of either eating wrong food or food in improper quantities, or in an improper manner; degen- erative changes in the body cells which interfere with either the absorption of food particles from the alimentary tract or the proper exchanges between the blood and the tissues ; pathological conditions in the blood itself; interference with the rapidity of blood flow; and a general lack of harmony in the function of the various important systems of the body. Pathological changes in the gastrointestinal tract, as they are found in tuberculosis present several different conditions, the ultimate effect of which in each case is the interference with proper absorption of nutriment. An almost constant condition in the alimentary tract in tuberculosis is a passive congestion. Resulting from the insufficient motion of the diaphragm and other inspiratory muscles there is always more or less splanchnic congestion present, the degree varying with the amount of dis- turbance in inspiration. This lessening of the inspiratory act causes the blood flow to be retarded through all the abdominal iAbderhalden : Defensive Ferments, William Wood & Co., New York, 1914. FACTORS INTERFERING WITH NUTRITION 253 organs and favors a general blood and lymph stasis, which inter- feres with the secretory function of the digestive glands, the motor function of the gastrointestinal walls, and the absorp- tion of nutriment from the alimentary canal. The amount of disturbance due to these conditions varies from that which is scarcely discernible clinically, to a very markedly altered func- tion in some patients who are suffering from more advanced lesions. Not only do we have a passive congestion as a result of deficiency in the respiratory act, but also as a result of nervous influences and weakened heart action, the latter particu- larly in advanced tuberculosis. Displacement of the various organs is also very common in tuberculosis. This is particularly true in the advanced disease as a result of malnutrition and the consequent absorption of the intra-abdominal fat, the general weakening of the musculature of the abdominal wall, and the wasting of the tissue supports of the various intra-abdominal organs. Aside from this we must also consider the effect of the pathological process above the di- aphragm. The diaphragm is often displaced and pushed down- ward by compensatory emphysema and at times by pleural ef- fusions and pneumothorax. Constant coughing also has an in- fluence in forcing the abdominal organs downward. Probably, what is of greater importance than the ptosis itself in these cases is the reduced intra-abdominal pressure under which the abdominal organs are compelled to work as a result of this loss of tissue and tissue tone. This ptosis affects, at times, all the abdominal organs. In advanced conditions it is not uncommon to find the stomach resting on the pubes; the cecum and transverse colon, together with the small intestine wedged tightly into the pelvic cavity, and the lower pole of the right kidney below the level of the um- bilicus. A dilated cecum is also frequently found. These ptosed organs, however, often functionate well and show no symptoms directly referable to the ptosis itself. Atony and dilatation are very common in advanced cases. The gastrointestinal tract is also subject to many reflex dis- turbances, the afferent impulse traveling from the pulmonary ends of the vagus and possibly the sympathetic, if we follow the 254 DIGESTIVE SYSTEM IN TUBERCULOSIS Continental physiologists, and the efferent being transmitted through the gastrointestinal branches of the vagus and sympa- thetic, to the ganglia which lie in the walls of the organ. I have recognized this gastric vagus reflex from the lung in several in- stances of hyperacidity which were increased by the focal re- action following large doses of tuberculin. I have also seen it in numerous instances during cavity formation in the lung, where, as a result of irritation of the pulmonary branches of the vagus, hyperacidity, reflex vomiting, and spasticity of the colon were produced. Neither must we forget the effect of toxins on the gastroin- testinal tract. These have a two-fold action. They act cen- trally through the splanchnics, exercising an inhibitory influ- ence upon digestive activity in general; and, particularly late in the disease, cause degeneration of the cells of the organ. Tuberculosis of the various portions of the intestinal tract and of the liver, pancreas, and spleen, must also be considered as part of the pathology which must be reckoned with. The Digestive Tract and the Vagus and Sympathetic Nervous Systems in Tuberculosis. — The part which the nervous system plays in the production of symptoms on the part of the gastro- intestinal canal during the course of clinical pulmonary tuber- culosis, is a very important one. As all internal viscera are innervated by both the vagus and sympathetic divisions of the vegetative system, and as these divisions antagonize each other in every viscus in which they meet, as described more fully in Chapter VII, it behooves us to study carefully the effect of cen- tral or peripheral stimulation of either of these systems which might occur as a result of the inflammation in the lung. As I have shown elsewhere 2 and discussed in Chapter VIII, the syndrome of toxemia as expressed clinically is that of gen- eral sympathetic inhibition. Its effect is that of a central stimulation of the sympathetic system; and its manifestations are as widespread as the organs innervated by it. No matter what the source of the toxemia, the expression is the same. 2 The Syndrome of Toxemia: An Expression of General Nervous Discharge Through the Sympathetic System, Journal American Medical Association, Jan. 8, 1916, vol. lxvi, pp. 84 and 85. VAGUS AND SYMPATHETIC TONUS IN ALIMENTARY CANAL 255 On the part of the gastrointestinal canal, toxemia manifests itself in inhibition of action. This is the system of nerves which diminishes salivary secretion, relaxes the esophagus, relaxes the stomach, inhibits gastric, intestinal, hepatic, and pancreatic se- cretion, relaxes the intestinal wall and decreases the motility of the gut. "When toxemia is present, the sympathetics are cen- trally stimulated by the toxins and peripherally by the extra adrenin which results from the splanchnic stimulation, and we have a chain of symptoms, varying, of course, according to its severity, such as; a decrease in appetite, coated tongue, di- minished gastric and intestinal secretions, and a deficient gastric and intestinal motility resulting in stasis and constipation. In tuberculosis the degree of toxemia varies greatly with the character of the disease ; so do the symptoms on the part of the gastrointestinal tract. Sometimes they are very severe and again they are negligible. Sometimes, even when a marked degree of tox- emia is present, no noticeable symptoms of gastric or intestinal origin will be noted. This can be explained on a rational basis by bearing in mind that tuberculosis is an inflammation in the lung, which irritates the pulmonary nerve endings belonging to the vagus; and, at the same time, stimulates the cells of the sympathetic division of the vegetative system, and that while both of these produce action in the gastrointestinal tract, no dis- turbance in equilibrium results. Peripheral sympathetic stimulation, like central stimulation of the same division of nerves may possibly cause inhibition of function in those organs which come in the path of its reflex action. Whenever a toxemia stimulates the central nerve cells of the sympathetic in pulmonary tuberculosis, the inflamma- tion at the same time stimulates the peripheral filaments of the vagus. The vagus, being the division of the vegetative system which is conservative in its action, when stimulated to a moder- ate degree, opposes the inhibiting influence of the sympathetic and in many instances wholly counteracts it. Appetite. — The appetite is decidedly variable in tuberculosis. During the periods of general depression, such as those which are manifested by discontent, discouragement, anxiety, fear and during pain; and also during periods of toxemia, the appetite 256 DIGESTIVE SYSTEM IN TUBERCULOSIS is usually diminished. At other times, it may be normal, or even above normal. The appetite is very important in tubercu- losis, both because of its influence on the amount of food taken and upon the digestion of the food after ingestion. During the entire period when toxemia is present and during the periods marked by the depressive emotional states that ac- company or occur during the disease, the appetite is usually very seriously lessened. At times, it is impossible for the pa- tient to eat sufficient food to nourish him. Owing to the lack of appetite, mastication of food, which is so essential to the proper division of the particles and also to its insalivation, is im- perfectly carried on. Often it is necessary that the great bulk of the food eaten be of such a nature that it can be swallowed rather than chewed. The result of this is that an extra burden is thrown upon the gastric and intestinal functions. While nor- mal gastric juice is able to take care of protein food, whether it be coarsely or finely divided ; yet a lack of proper insalivation, particularly of the starchy food, has a very important inhibi- tory action upon gastric digestion. Maxwell 3 shows experimentally that substances in suspen- sion or in colloidal solution have the power . of absorbing enzymes, thereby inhibiting their activity. He has also shown experimentally that unboiled starch administered in intact grains does not hinder the action of pepsin; but when starch has been boiled and left in colloidal form, it seriously inter- feres with digestion by the absorption of the proteolytic enzyme. Thus, the time interval for the peptic digestion may be in- creased fourfold in the presence of a 2 per cent starch solution. From this the conclusion is drawn that all cooked farinaceous foods, such as rice, sago, potato, bread, and oatmeal, interfere with peptic digestion unless they are thoroughly insalivated. This work emphasizes the importance of chewing farinaceous food thoroughly. Salivary, gastric, and intestinal digestion are more or less closely related; yet each has its own particular function and, unless carried on properly, interferes with, or throws an ex- tra burden upon the process next lower. 8 The Relation of Salivary to Gastric Secretion. Biochemical Journal, 1915, vol. ix, p. 323; quoted editorially in the Journal of the American Medical Association, vol. Ixvi, March 4, 1916. GASTRIC DISTURBANCES IN TUBERCULOSIS 257 Disturbance on the Part of the Stomach. — Our idea of the stomach and its importance as an organ of digestion is very dif- ferent from what it was a few years ago. We cannot lose sight of the fact that it may show many disturbances in function, due to action outside of itself. While the stomach may be looked upon as a reservoir for food, retaining it until it is ready to be passed on into the intestine ; yet certain important changes take place in the food during its stay in this reservoir which are preparatory to further digestion; and it is necessary that this or- gan have proper secretory and motor power if normal relation- ships are to be maintained in the remaining portion of the diges- tive canal. The importance of the quality of the gastric contents as dis- charged into the duodenum cannot be overestimated if our newer theories of secretory and motor control of the gastrointestinal tract are to be held. The hormone theory as it affects digestion presupposes a nerve stimulus awakened by the smell, taste, and intake of food. Through this the gastric hormone is set free into the blood and finds its way to the secretory glands of the gastric mucosa and stimulates them to the production of gastric juice. When the acid gastric contents are discharged into the duodenum, they stimulate the formation of another hormone, which passes into the blood and in its circulation exercises its selective action upon the secretory glands of the intestinal wall, pancreas and liver, setting free the digestive ferments of these various organs. Henry Harrower 4 has discussed this matter in a monograph well worthy of perusal. The hormone theory, like all other contributions which have added to our knowledge of the function of the gastrointestinal tract, and which have pointed the way to a better understanding of the nervous derangements which are found in our every day practice, emphasizes the fact that disturbances of digestion cannot be considered as belonging to any one portion of the tract alone, but to it as a whole. We must still recognize the alterations which occur in the gastric secretion because they are very important in their bear- ing upon further digestion. If we have abnormal secretion in 4 Practical Hormone Therapy, Bailliere, Tindall and Cox, London, 1914. 258 DIGESTIVE SYSTEM IN TUBERCULOSIS the stomach in tuberculosis, we are apt to have abnormal secre- tion in other parts of the gastrointestinal tract from the same cause; abnormal motility, also; because the motor function of the intestinal canal depends on the stimulus received from the acid contents of the stomach. In early tuberculosis increased acidity, probably of reflex origin, is quite common. A general, increased tone is present affecting all of the vagus branches as suggested by Eppinger and Hess. 5 During the late stage of the disease, especially when toxemia is marked, a deficiency in hydrochloric acid is the rule, although this condition often alternates with nor- mal amounts of acid, or with a hyperacidity. The relaxed con- ditions produced by toxemia and its action upon the sympa- thetics and by the general degeneration present, contrary to what we might think, are not always accompanied by a deficiency of hydrochloric acid. Not infrequently do we find a hypersecre- tion during these periods. This can be explained on the ground that the reflex stimulation of the vagus is stronger than the com- bined reflex and central stimulation of the sympathetics. Inas- much as control of the pylorus depends to a considerable extent upon the acidity of the secretion, as it passes from the stomach into the duodenum, we must recognize the importance of the qual- ity of the gastric juice because of its effect on the entire canal. At times we see, especially in the later stages, a decided in- crease in the amount of secretion which remains in the fasting organ. This may have either a normal, a deficient, or an in- creased percentage of acid. This condition is often accompanied by more or less troublesome symptoms. It seems to be associated often with atony and dilatation. Atony and dilatation of the stomach are usually associated with a downward displacement of the organ. This dilatation may be due to errors in diet, overfeeding, altered secretion accompanied by abnormal gas formation, obstruction of the pylorus, or to a general degeneration of the cells of the wall of the organ (I have seen cases postmortem where the stomach was dilated to such an extent that its capacity was three or four times its normal). Hypochlorhydria is often found in tuberculosis in patients in 6 Die Vagotonic, Sammlung, Klinischer Abhandlungen, von Noorden, Heft. 9 u. 10, Berlin, 1910. HYPOCHLORHYDRIA 259 whom there is a generally decreased vagus tonus. In such, and usually in others, there is a deficiency of acid during times of acute toxemia owing to the fact that the toxins stimulate the sympathetics centrally and inhibit the gastric secretion. Hypochlorhydria. — There is a certain class of individuals who naturally have slow digestion. It would be manifestly erroneous to expect the spare asthenic to digest as rapidly and as well as the sthenic or hypersthenic individual. When those of the hypo- sthenic and asthenic type develop tuberculosis the question of nutrition usually becomes a more serious problem than it does in the stronger individuals. The toxemia of tuberculosis, added to the already slow digestion makes a serious complication. Since toxemia and states of anxiety, disappointment, and dis- couragement, as well as painful conditions when present, stimu- late the sympathetics and cause a general inhibition both in the seeretory and motor functions of the entire gastrointestinal canal, it can be seen that these have a tendency to retard diges- tion and produce disturbed motility, with stasis of the bowel contents. This is again followed by absorption of poisons from the alimentary canal which further depresses the digestive func- tions. The effect of these factors is greater upon those with nat- urally slow digestive function than upon those with function nor- mal or above normal. When suffering from hypochlorhydria, if only temporary, it is well to urge patients not to eat large quantities of food until this condition is corrected. The best foods under these circum- stances are those which have rather a stimulating effect on the gastrointestinal tract. Meat extracts, strong consomme, meat itself and dry toast, well chewed, stimulate secretion. Dilute hydrochloric acid, 5 to 10 drops taken after meals is of consider- able value. The following prescriptions I have used to ad- vantage : F* Acid hydrochlor dilut 25.00 Glycerin 25.00 Pepsin scales 50.00 Aq. dest. q. s. ad. 100 M. Sig.: 1 to 2 teaspoonfuls in water one-half hour after meals. 260 DIGESTIVE SYSTEM IN TUBERCULOSIS I£ Tinct. nux vom. 12.00 Tinet. cinchon, q. s. ad. 100.00 M. Sig.: One teaspoonful in water 20 minutes before meals. On the other hand, if the deficiency is chronic, then the patient must be fed liberally, using a diet which will stimulate secretion and favor regularity of bowel movement. At the same time, hy- drochloric acid should be administered. General measures for improving the patient's metabolism are of the greatest impor- tance. Hyperchlorhydria. — Hyperchlorhydria, contrary to the gen- eral belief, is quite common in pulmonary tuberculosis. As Ep- pinger and Hess have well pointed out, there is a large class of individuals which may be said to have naturally an increased vagus tone. The vagus nerve is the nerve which presides over secretion and motility for the gastrointestinal canal ; consequent- ly the vagotonic would naturally have an ample acid secretion. Those who are not vagotonic naturally could be rendered so by stimulation of the vagus alone; or by stimulating both vagus and sympathetic systems, but in such a manner that the vagus stimulation predominates over the sympathetic. During toxemia in pulmonary tuberculosis, as previously men- tioned, the sympathetic system is stimulated centrally by the toxins and peripherally by the inflammation in the lung and adrenin which is increased by the central sympathetic stimula- tion; and, the vagus is stimulated peripherally. As a result of this, sympathetic stimulation is nearly always predominant during toxemia, at least to a certain extent. As soon as the acuteness of the toxemia passes away, and the central stimulation of the sympathetics lessens or ceases, then in the great majority of cases of tuberculosis, the patient passes into a condition of rela- tively increased vagus tonus. His appetite improves and his digestive powers are even above normal. A state of hyperchlor- hydria often exists under these conditions. As a rule it is not sufficient to cause discomfort; at other times it is necessary to afford relief to the patient. Sometimes hypersecretion only is present without an increase in the amount of acid. Increased acidity is often accompanied by a stasis of the in- HYPERCHLORHYDRIA 261 testinal contents and a spastic constipation, both symptoms being due to increased vagus tone. The explanation of this condition is that the peripheral stimulation of the vagus by the inflammation in the lung results as a rule in the vagus impulse being stronger than the sympathetic stimulation and the conservative forces pre- dominating over the inhibiting influence of the sympathetics. In case of a marked hyperchlorhydria all stimulating food should be eliminated. Coarse foods which are likely to irritate the stomach should also be withheld from diet, such as lettuce, tomatoes, cabbage, celery, and coarse bread. Foods should be confined to the soft, non-irritating type. The food should be either wholly unseasoned or seasoned very lightly. The secre- tion of hydrochloric acid can be depressed somewhat by the use of atropin, % 00 of a grain being given three-quarters of an hour before each meal. This quantity, however, should, at times, be increased and should usually be pushed to the point of dryness of the throat. Atropin is particularly effective in those naturally vagatonic and where the condition is a result of vagus stimula- tion without organic lesions such as that caused by the pulmon- ary reflex. When due to ulcer, appendicitis, or disease of the gall bladder, it may be of limited or no value. Its use should be per- sisted in for a prolonged time. Bromides are also valuable in these cases. From 10 to 30 grains of bromide of soda may be given before meals although its ac- tion is not as certain as that of atropin. A very important point in the treatment of hyperchlorhydria is to neutralize the acid because it not only produces discom- fort in the way of a burning sensation, but, where we have large quantities, it has a tendency to produce spasm of the pylorus and interfere with the emptying of the stomach contents into the duodenum, which, if maintained long enough, will favor dila- tation. It also throws a great burden upon the intestinal secre- tions to neutralize the excess of acid when it enters the duo- denum, and thus delays the emptying of the stomach. For neu- tralizing the acid the old favorite combination of subcarbonate or subnitrate of bismuth, bicarbonate of soda and carbonate of magnesium, is excellent. These may be used in equal parts by weight, one teaspoonful to be given two or three hours after 262 DIGESTIVE SYSTEM IN TUBERCULOSIS meals at the time when the burning begins. The bismuth has a tendency to depress the secretion of the acid, while the soda and magnesium neutralize it. If the patient is inclined to con- stipation the magnesium may be increased and the bismuth be decreased in amount. If, on the other hand, there is a tendency to diarrhea, the bismuth may be increased and the magnesium reduced ; or, if this is not sufficient to counteract the acidity, more soda may be added. At other times plain bicarbonate of soda may be used in teaspoonful doses. It is necessary to explain to the patient the necessity of tak- ing sufficient of the salts to neutralize the acid ; otherwise he will not understand and is apt to take small amounts and only partially neutralize and in this way obtain only partial relief. Sometimes an absolutely meat-free diet persisted in for a long time seems to help most; although, at first the acidity is worse because of the lack of albumin to combine with the acid. I have found in my work among the tuberculous, however, that a gen- eral diet is the best; and, inasmuch as I feel that some proteid is essential, I do not like to eliminate meat from the diet, and usually try to control the acidity as well as possible without eliminating it, at least, until such time as the condition of the patient will permit of more rigid diet without risk. When due to ulcer of either the stomach or duodenum, these conditions must receive appropriate treatment. Dilatation of the Stomach. — There are many factors in tuber- culosis which tend to produce dilatation of the stomach. Some of these are avoidable, others are not. In the early stages of the disease it is not apt to occur unless there is some obstruction of the pylorus. In chronic cases it formerly was often found as a result of overfeeding. It is in the late cases, however, after de- generative processes have set in and the Avails have become atonic that this condition becomes a serious factor. When this condi- tion has been attained the digestive juices are, as a rule, impaired ; the muscles are weakened; motility is lessened; the food re- mains in the stomach longer than it should; gases develop, and the organ dilates. This often occurs during a prolonged period of toxemia when the inhibitory influences of the sympathetic nervous system are predominant. Again, it occurs in hyperacidity DILATATION OF THE STOMACH 263 when the spasm of the pylorus prevents its opening naturally. Slight degrees of dilatation may be present without trouble- some symptoms arising; and a stomach when dilated to a slight degree may again become functionally normal. When, however, the severe degrees of dilatation that are encountered in advanced tuberculosis take place, in which, through toxemia, marked de- generation has become established, and delayed and imperfect digestion has resulted, the symptoms become extremely trouble- some and are also difficult to relieve. Patients suffering from dilatation of the stomach complain of loss of appetite, feeling of fulness, nausea, and vomiting. They may think they will enjoy a meal, but are usually satisfied when they have eaten a few mouthfuls. They also have a feeling of fulness on eating small amounts of food. This common symp- tom of dilatation — feeling of fulness — has been shown by Hertz and his co-workers 6 to be due to tension exerted on the circular muscle fibers of the stomach. Changes in the circular muscles are brought about by a reflex from the esophagus during the act of swallowing. When food passes through the esophagus it re- flexly stimulates the circular muscles of the stomach to dilate and make room for the additional food which enters. If food is eaten rapidly and sufficient time is not allowed for the circular coat to dilate, a feeling of fulness results; or, if the stomach is al- ready completely relaxed, as it is in cases of marked dilatation, then the taking of food stimulates the fibers to further relaxa- tion, just the same as in the non-dilated organ; but, inasmuch as the circular muscular coat is already fully relaxed, further re- sponse to the esophageal swallowing reflex cannot do more than to attempt to relax an already relaxed muscle. The result, how- ever, is the same feeling of fulness, as is noted when the organ is fully distended by food; because the circular fibers are sub- jected to increased tension after they are fully relaxed. I have found it best, if this condition is severe, to feed the patient at frequent intervals; to reduce the amount of liquid taken with the meals to the minimum; and, above all else, to withhold from the diet food which is slow of digestion as well as such articles as produce gas. However, if the dilatation is not too 6 The Sensibility of the Alimentary Canal, Oxford University Press, London, 1911. 264 DIGESTIVE SYSTEM IN TUBERCULOSIS severe and not causing too much disturbance a liberal diet should be insisted upon, for the condition can only hope to be improved as the general health of the patient improves. Concentrated nu- tritious food should make up an important part of such a dietary. Lavage is sometimes valuable in these cases. Strychnine seems to offer some aid; but building up the patient where this is pos- sible, is of greatest importance. Unlike dilatation in the in- dividual who is otherwise strong and healthy, we here have mal- nutrition and general lack of tone as a more important factor than obstruction. Disturbance on the Part of the Intestines. — Many of the non- tuberculous complications on the part of the intestinal tract are also extremely common in tuberculosis. Enterocolitis. — This complication is a very common one. It may be of slight degree or it may be very severe. It may be due to errors in diet, or result from an obstinate constipation and the use of laxatives to which so many people are addicted ; or, in tu- berculosis, it is probably at times due to toxemia; and, at times, to a venous congestion in the intestinal wall, the latter being a constant factor of this disease. The excessive use of raw eggs will produce it. According to the severity of the case these patients complain of loss of appetite, nausea, feeling of fulness and sometimes distension of the entire abdomen, accompanied quite often by colicky pains. Flatulence, general lassitude, nervous irritabil- ity and sometimes depression are common. The entire course of the colon may be sensitive to pressure. The inflammation usually involves both the large and small intestine. Constipa- tion may be present; but, if so, it is apt to alternate with loose movements or diarrhea. The patient usually passes one or two soft stools a day and has considerable gas. These patients may usually be relieved by proper treatment although we may never be sure that we have arrived at a permanent cure, for relapses are extremely common. Treatment depends upon the severity of the case. The most important measures in the treatment of this com- plication are the relief of mental depression, rest and diet. It is well for the patient to understand that the maintenance of a ENTEROCOLITIS 265 good result depends not on medicines but on persistently fol- lowing rational living and appropriate diet. Remembering the effect of emotions on the digestive tract, the importance of op- timism cannot be overestimated. If the condition is at all severe, rest in bed is essential for the proper handling of this compli- cation. In severe cases I put the patient to bed and eliminate all questionable foods from the diet. At first, nothing but gruel and milk or gruel and buttermilk are given, making the gruel by boiling rice or barley until it becomes a pulp, and straining this through a cloth. Water is then added to make it the con- sistency of thick soup. A glass of gruel and a glass of milk or buttermilk is given three or four times a day. In some instances milk will not be tolerated. Then gruels and soups may be used exclusively. In some cases this line of treatment proves wholly inadequate. Under such conditions we should recall the pos- sibility that the colloidal boiled starch may be interfering with the peptic digestion. Sometimes it is best to eliminate starch wholly from the dietary. Colonic injections of starch water and bismuth are help- ful. Starch water is made by boiling the starch and adding water so that it is of such consistency that it passes through the syringe easily. To each quart of starch water one dram of sub- nitrate of bismuth is added. This is used quite warm. It is in- jected into the rectum slowly and the patient is instructed to retain it at least for half an hour, or even longer, if possible. This is given once or twice a day at first; and, as the patient improves, the intervals are lengthened. Hot packs to the ab- domen for two hours once a day or one hour twice a day are employed. As medication the patient is usually given a tea- spoonful of castor oil each night. This method has proved very satisfactory in handling these patients. Now that we fully understand the antiperistaltic movement of the colon we recognize that it is not necessary to use high flushings, as we formerly did, because fluids thrown into the rectum will soon travel the entire course of the colon ; and even through the ileocecal valve if patulous. Sometimes patients will complain that they cannot take large enemas without feel- 266 DIGESTIVE SYSTEM IN TUBERCULOSIS ing ill. They have feelings of faintness, colicky pains, and nausea owing to irritation of vagus endings. The following diet has proved very satisfactory in the treat- ment of the majority of patients having entercolitis. Diet Permitted in Severe Cases. — At first, gruel (rice or bar- ley), milk (diluted with half water or Vichy) or buttermilk; or gruel soups where milk is not tolerated. As the patient improves, the following are permitted. Rice, toast, or stale bread, cereals, soups, sago, noodles, macaroni, baked or mashed potato, eggs, either raw, soft boiled, or poached. Moderately Severe Cases. — These cases may have all of the above, and in addition such light vegetables as spinach, carrots, cauli- flower, peas, and squash; and meats sparingly. Mild Cases. — These cases may have the above with whole wheat bread, meats, fish, and fruit sauces. In colitis it is always best to take foods warm and avoid such cold foods as ice cream, cold milk, and cold water. Hot water may be taken to advantage. If a more laxative diet is required prunes, oatmeal, and honey may be added. Foods Forbidden. — Coffee (especially strong), all acid or raw fruits, legumes, cheese, cabbage, smoked meat and fish, fat meat, pork, veal, fresh bread, and pastry. In cases accompanied by severe diarrhea, all extracts of meat should be withheld from the diet until acute symptoms have disappeared. Intestinal Stasis. — The mechanical factors of digestion have assumed a much more important place in medical literature in recent years than formerly. In America this has been largely through the splendid work of W. B. Cannon. 7 We were for- merly accustomed to speak only of the peristaltic action of the small intestine, but we now know that there is a definite peri- staltic action of the stomach and of the large bowel. In tuber- culosis stasis is extremely common. The peristaltic movements of the intestines are increased by the vagus and inhibited by the splanchnics, both of which are stimulated in tuberculosis, re- sulting now in spastic constipation and again in that of the 7 The Mechanical Factors of Digestion, Longmans Green & Co., New York, 1911; also Bodily Changes in Pain, Hunger, Fear, and Rage, D. Appleton and Co., New York, 1915. INTESTINAL STASIS 267 atonic type. Inasmuch, as congestion of the intestinal veins is present to a greater or lesser extent in all pulmonary inflam- mations, we have interference with the action of the peristaltic wave from this cause, even in early cases; while we have the marked toxemia and degeneration added later. There are several points in the alimentary tract where food is naturally hindered in its downward progress. The normal passage of food should require somewhere in the neighborhood of twenty-four hours in passing from the stomach to the rec- tum. The first point of delay is that of the pylorus, which is presided over by certain reflexes which depend primarily on the acid content of the stomach, and, secondarily, upon the neu- tralization of these acid contents after they pass into the duo- denum. In case of an increased acidity in the stomach we have a reflex spasm of the sphincter which retards emptying and often- times leads to more or less dilatation of the organ. The pylorus may be kept closed reflexly by inflammations in the neighbor- ing organs. This is particularly evident at times in cases of appendicitis, duodenal ulcer, and cholecystitis. The next point is that of the ileocecal valve. The purpose of the closure of the ileocecal valve is probably to favor absorption. Food naturally requires about four or five hours in passing from the stomach to the ileocecal valve. When such irritations as those resulting from cholecystitis, chronic appendicitis or tu- berculosis of the appendix, or inflammatory conditions about the head of the cecum, are present, the opening of the sphincter may be interfered with and stasis in the ileum result. The same is due at times, and probably more often, to mechanical obstruction. Normally, when food enters the stomach, the ileo- cecal valve is reflexly opened; but any irritation in the neigh- borhood of the valve itself may prevent this opening and favor stasis. The cecum and ascending colon is a sort of churning place for the food. Like the stomach this is another reservoir where it is retained for a considerable period of time. The passage of food along the colon is very different from that in the small intestine. Here, instead of being pushed along by the small peristaltic waves, such as are present in the small intestine, the particles of food are carried onward more or less 268 DIGESTIVE SYSTEM IN TUBERCULOSIS en masse by massive peristaltic waves and collect in certain portions such as the middle of the transverse colon, the pelvic colon, and the rectum. With both the central and peripheral stimulation of the sym- pathetica, the peripheral stimulation of the vagus, the venous congestion of the intestines, the degeneration in the walls of the gut, the displacements such as are common in tuberculosis, particularly after the stage of wasting has been reached, stasis in both the ileum and colon become exceedingly common and also become matters of extreme importance. The ill effects of stasis upon the patient are mainly due to absorption of poisonous materials which generate during the slow passage of the contents in the bowel which act upon the brain centers producing general instability of function. Not only do we have the general effects of the absorption of these deleterious products to deal with, but we have a disturbance in the rhythmical function of the gastrointestinal tract. These pa- tients suffer from toxemia, which is expressed in the symptom- complex: headache, malaise, aching more or less severe through- out various portions of the body, rapid heart action, alteration and depression of appetite, and general inhibition of the gastro- intestinal functions, which results at times in marked dis- turbance of nutrition. Often flatulence and colicky pains are troublesome. This toxemia is often preceded by a retardation of the intestinal contents due to stimulation of the vagus. Studies in visceral neurology, as well as clinical observation, lead me to believe that, omitting cases of definite obstruction, increased tonus of the intestinal branches of the vagus is the most fre- quent underlying cause of intestinal stasis. The relief of stasis is not a simple matter because patients who suffer from it, even those without tuberculosis, suffer more or less from a disturbed nerve equilibrium. It is important not only to correct the stasis for the time being, but to keep it corrected ; to improve the habits of the individual ; and to re- educate the nervous system. Inasmuch as this is a part of the general treatment of tuberculosis anyway, these patients should improve by the general methods which are employed in the handling of this disease. INTESTINAL STASIS 269 Stasis cannot be cured by cathartics. It is important to try in every way possible to obtain the normal onward movement of the material in the gastrointestinal canal. It is very dif- ficult to discuss this question aside from constipation, although the two are not identical. Such measures should be utilized as favor a normal passage of the food in the intestine, because by so doing the decomposition and fermentation which other- wise take place are prevented and the ill effects of absorption are avoided. Aside from this, the production of gases which are more or less harmful in these cases in that they produce dilatation and also stimulate to irregular contractions and the production of colicky pain, may be avoided. Bran, agar-agar, and paraffin oil are all valuable in the treatment of these cases. Hot applications to the abdomen have a splendid effect in re- laxing the spasm which may be produced by the irritating gases. Sometimes a course of some of the mineral waters, while theoretically contraindicated, is allowable for it seems almost necessary to administer some direct relief. We are obliged to deal somewhat differently with the tuberculous, with his toxemia and degeneration, from what we do with the non-tuberculous. Such waters as Hunyadi Janos, Apenta, and many that we have in our own country, such as Pluto and Abilena, may be used. The use of these should only be temporary and with- drawn after serving their purpose. These patients should be encouraged to drink large quantities of plain water, particu- larly warm water. Atropin should be used freely and persist- ently. Constipation. — There are many factors in tuberculosis which tend to the production of constipation or to the aggravating of such a condition when it already exists. These are: 1. The habits of previous years which have so often caused neglect of this important function of the bowels. 2. Faulty habits of eating which are more or less compen- sated for as long as the patient is well, but which are magni- fied by illness. 3. Disturbances of the normal physiologic rhythm of the gastrointestinal function, whether due to motor or sensory change or alteration in position or contour of organs. 270 DIGESTIVE SYSTEM IN TUBERCULOSIS 4. The toxic and reflex influences through the sympathetic and vagus nerves and the degenerations which are essentially due to the tuberculous process. 5. The splanchnic congestion which is produced by the dis- turbance in the function of the respiratory muscles and the con- sequent reduction and limitation of the inspiratory act, as de- scribed more fully on page 301. 6. The limitation of exercise made necessary by the activ- ity in the tuberculous focus. 7. The eating of concentrated foods to the exclusion of those of the more bulky type, partly from former habit, partly be- cause of the misguided notion that concentrated foods are the only ones of value in tuberculosis, and partly because a dis- turbed appetite and repugnance for food make it difficult if not impossible to chew the food of a more bulky nature. I have found in my own work that the classification of con- stipation into atonic and spastic, as suggested by Cohnheim, 8 is a very practical one from the standpoint of therapy. We find more or less constipation in a very large per cent of our cases. In some it is of the atonic type, in others of the spastic type, and more generally, a combination of the two. The treatment of these two types is radically different, consequently difficulties arise, particularly in the mixed type. Hertz 9 also recognizes two types of constipation differing some- what from Cohnheim. He says: "As a result of my investigations with the x-rays on the motor functions of the intestines in health and disease, I con- cluded that all cases of constipation can be divided into two classes: in the first, which may be called intestinal constipa- tion, the passage through the intestines is delayed, whilst defe- cation is normal; in the second class, for which I have adopted the term dyschezia, there is no delay in the arrival of the feces in the pelvic colon, but their final expulsion is not ade- quately performed." Of these two types of constipation it can readily be seen that, that of the spastic type or intestinal type of Hertz is 8 Disturbances of the Digestive Canal, Translated by Fulton, J. B. Dippincott Co., 1909. s The Sensibility of the Alimentary Canal, Oxford University Press, 1911. CONSTIPATION 271 more serious than the atonic, because the contents are delayed in the passages higher up in the canal where the absorptive powers of the gut are greater and at a time when decomposi- tion of the contents is more apt to occur. Consequently spastic or intestinal constipation is accompanied by greater toxemia. It is also accompanied by the formation of gas and sooner or later leads to destructive changes in the wall of that portion of the bowel affected. The patient suffering from atonic constipation, on the other hand, does not suffer from toxemia to so great an extent neither does he experience the deleterious effect of gas in the bowel. Atonic Constipation. — Atonic constipation is that type in which the bowel itself seems to have lost its natural response to stimulation. This type of constipation is usually characterized by a large dry stool. In this form of constipation gas is not a prominent symptom, in fact it is often entirely absent. Of- ten the only complaint of the patient is the inability to have a normal stool. Sometimes, however, they have toxic symptoms as feelings of dullness, headache, malaise, and the lack of de- sire for work. These patients are in the habit of relieving themselves either by the use of enemas or laxatives, both of which answer the purpose for the time, but in the end prove harmful. One measure of great importance in the treatment, particularly of this form of constipation, is somewhat difficult to carry out in tuberculosis, — that of exercise. Exercise is valu- able; but we are forced in treating tuberculosis, particularly during the active stage, to keep the patient quiet. The wasting which occurs in advanced cases and the congestion of the in- testinal tract have a tendency to increase constipation when present, no matter whether it be of the atonic or spastic type. The first thing in the treatment of all forms of constipation is to get away from cathartics. In fact, they of themselves will eventually aggravate the very condition which we are try- ing to eliminate. Atonic constipation requires that type of food which fur- nishes large amounts of waste matter. It should be rich in cellulose and of such a character as will mechanically stimulate the mucous membrane. 272 DIGESTIVE SYSTEM IN TUBERCULOSIS It is my custom to have these patients drink one or two glasses of cold water on going to bed and also the same on getting up in the morning. Fruit juices such as lemonade and orange juice may be used in the morning before breakfast to ad- vantage. Tea and coffee should be used sparingly or not at all. Buttermilk, at least two days old, may be used. Butter should be used freely. Nearly all kinds of fruit are allow- able in this form of constipation. Vegetables of the coarser varieties, such as lettuce, celery, asparagus, string beans, spin- ach, legumes, and tomatoes, are extremely valuable, so are coarse breads and coarse cereals. Meat and eggs produce a small amount of residue but, at the same time, should be allowed in moderation because of the fact that these patients require them in their dietary. Any mechanical derangement of the gastrointestinal tract should be corrected if possible. Massage is of value in this form of constipation. Warm olive or linseed oil enemas given at night are effective in softening scybalous masses if present. Be- ginning with one ounce this may be increased to four or five ounces. The patient should retain this over night. This may be used at first every night and then the interval should be gradually lengthened until it is used only once a week. Some- times, at first, it may be necessary to give these patients some of the laxative mineral waters, although they should be with- drawn as soon as possible. For such purposes Hunyadi Janos, Apenta, Pluto water, Carlsbad Salts, or plain phosphate of soda may be used each morning before breakfast. The addition of one or two tablespoonfuls of bran to the diet two or three times a day; or agar-agar, one teaspoonful to a tablespoonful twice a day is often of great benefit. What is desired is a normal motor response on the part of the intestinal muscles. Hertz 10 speaks of that type of constipation which results from a delay in expelling feces from the rectum as dys- chezia. This is allied to the atonic type. I will quote his dis- cussion of the causes which operate to produce this type. It will be seen how the conditions enumerated above as being present in tuberculosis will operate in both delaying the pas- 10 The Sensibility of the Alimentary Canal, Oxford University Press, 1911. ATONIC CONSTIPATION 273 sage through the intestine and in emptying the rectum when it has been reached. He says: "The most common cause of dyschezia is the habitual disregard of the call to defecation on account either of ignorance or laziness or of fear of pain in diseases of the anus and the neigh- boring organs. I have already described how the sensation of fulness in the rectum passes off owing to relaxation of the tonic contraction of its muscular coat, if the call to defecation be disregarded. If it is again disregarded after its return on the arrival of more feces in the rectum, further relaxation occurs. More and more feces accumulate in the rectum, the muscular coat of which becomes more and more relaxed. As the force required to empty the rectum when overdistended with feces is much greater than that required to empty it under normal conditions, evacuation is now likely to be incomplete, even if a great effort be made. Consequently feces are constantly pres- ent in the rectum instead of only for a few minutes before def- ecation, and the lumen of the rectum is permanently increased owing to the atony of its muscular coat. It has sometimes been recommended that patients, who are constipated as a result of irregularity in their habits, should attempt to open their bowels after breakfast, but should not obey the call to defecation if felt at other times during the day. Our observations show that this teaching is wrong, and that, in addition to the regular morn- ing effort a response should be made to every call, however in- convenient the time. For the occurrence of a call to defecation always means that for some reason feces have just passed from the pelvic colon into the rectum; the relaxation of tone which follows neglect of the call is undesirable, particularly in pa- tients with dyschezia, in whom a certain degree of atony is al- ready present. "Dyschezia may be due to various other causes, such as weak- ness of the voluntary muscles of defecation and the assumption of an unsuitable position during defecation. But whatever the primary cause, the final result is the same. The incomplete evac- uation of the rectum results in the accumulation of feces and in atonic dilatation. "I believed at first that the absence in dyschezia of any sen- 274 DIGESTIVE SYSTEM IN TUBERCULOSIS sation when the rectum contained feces was due to a blunting of the sensibility of the mucous membrane as a result of the ir- ritation produced by the constant presence of feces. This view was shown to be erroneous by our observations that the 'rectal mucous membrane is normally insensitive to tactile stimulation, and that the call to defecation depends upon the sensibility of the muscular coat of the rectum. The few experiments, which I have at present had the opportunity of making, suggest that the muscle-sense is not impaired in most cases of dyschezia, as the intrarectal pressure required to produce the call of defeca- tion is not greater than in normal individuals. The dyschezia depends upon the atonic dilatation of the rectum, an abnormally large quantity of feces being required to exert the normal ade- quate pressure. In extreme cases a blunting of the muscle-sense may also occur; in such cases the rapid and considerable dis- tention produced by an enema injected with an ordinary syringe fails to produce the artificial call to defecation, which in most cases of dyschezia results in a movement of the bowels. "There is, however, an entirely distinct class of dyschezia which depends upon deficiency of the muscle-sense of the rec- tum. Congenital deficiency probably causes the dyschezia, which occurs not uncommonly in infants, in whom the slight additional distention produced by the introduction of a finger or a piece of soap into the rectum results in an adequate stimulus. In the majority of cases the muscle-sense develops as the infant grows older, but congenital deficiency is occasionally the starting-point of dyschezia which lasts through life." The place of low enemas in the relief of a loaded colon de- serves some consideration. Realizing the importance of normal evacuations some faddists have gone so far as to attempt to cure all ills by injections of water into the bowel. Others, appre- ciating that this was a fad which was subject to abuse and ca- pable of harm, have refused to see any good in it and have preferred to resort to the use of laxatives of various kinds. If the emptying of the lower bowel depends upon the muscle-sense, in case the muscle still possesses expulsive power, an enema should furnish the normal stimulus and be a natural measure for relief. It also has an added advantage of softening the feces. SPASTIC CONSTIPATION 275 When trying to get patients suffering from atonic constipation away from cathartics, I believe this one of the best measures. The amount of water should not be too large and is best at low temperature which stimulates the tissues while the warm re- laxes them. While the small enema of low temperature is of value in atonic constipation it is not so valuable in the spastic type because the delay in passage is due to increased tone and is farther up in the canal. This type is produced by too much muscle stimula- tion. Relaxing measures here are most valuable. If injections are used in this type, they should be quite warm and introduced in such a manner as to allow the water to travel upward toward the cecum. While the low enema for the relief of atonic con- stipation should not be held, that for spastic should be retained for several minutes. Spastic Constipation. — Spastic constipation is very different from atonic constipation in its nature as well as in its demands for treatment. While atonic constipation is due to a failure of the bowel to respond to stimuli, spastic constipation is due to an increased vagus tonus, and an irritative condition of the in- testinal tract in which the colon is the seat of spastic contrac- tion. Spastic constipation is extremely common in cases of hy- perchlorhydria. Every now and then there is an absorption of toxins with the resultant toxic syndrome. The patient feels dull, has a slight headache, and loses ambition. The bowel move- ment is entirely different in form. It is usually of soft con- sistency, small, ribbon-like in appearance, and the patient ex- periences an unsatisfied feeling after the bowels have moved. This form of constipation is associated with flatulence. Gas is a very common factor and is often accompanied by colicky pains. Individuals who are naturally of the vagotonic type are very prone to suffer from this form of constipation. Cohnheim says that every case of chronic constipation that runs its course with attacks of pain belongs to the spastic variety, in which inflam- matory and catarrhal changes of the intestinal tube are demon- strable. Patients suffering from spastic constipation are espe- cially harmed by laxatives. In some cases laxatives even in- crease the constipation. I have seen cases where cathartics 276 DIGESTIVE SYSTEM IN TUBERCULOSIS caused so much irritation that defecation was almost impossible. The principles of the treatment of spastic constipation are the opposite from those for atonic constipation. In atonic con- stipation we endeavor to irritate and awaken in the bowel a response to stimulation; while in spastic constipation, we en- deavor to allay all irritation and remove all factors which have a tendency to provoke irritation. Eest is very important in these cases. Patients do better when kept in bed for a time. Mechanical measures such as massage are contraindicated. Hot packs to the abdomen for a period of two hours daily are of great value. The oil treatment, as mentioned in atonic constipation, is of great importance; both the administration of paraffin oil by the mouth in doses of one or two ounces per day, and the ad- ministration of the oil enemas to be retained at night. Diet is most important. Foods which produce much gas, like- wise those which contain large quantities of residue, should be eliminated from the dietary. These patients should not drink cold water; but large quantities of hot water aid in relieving spasm. One or two glasses should be taken at bedtime and the same again on arising in the morning. Weak tea or coffee may be used sparingly, although the patient is better without them. Sometimes these patients may be allowed orange juice in the morning, although, at other times, I find it is apt to produce colic ; and, if hyperchlorhydria is present, it is contraindicated. Milk, buttermilk (at least two days old), all soft vegetables such as peas, carrots, mashed potatoes, baked potatoes, squash, hom- iny (if chewed thoroughly) and cereals may be used. Vegetables are best in purees. Spinach, Brussels sprouts and cauliflower may be used at times for variety, but not often; cauliflower, particularly being prone to produce gas. Fruits such as pears, peaches, and prunes are valuable. Honey, marmalade, jellies and jams which have a laxative effect through chemical action, are very useful. Stale white bread, toast, and zweibach may be used, but hot bread, biscuits, and coarse bread are not per- missible. Green vegetables must sometimes be wholly eliminated from the dietary until the symptoms have been relieved for some time. There are two drugs which are of great value in this type SPASTIC CONSTIPATION 277 of constipation, atropin and bromides. Atropin can usually be given in 1/200 grain doses three times a day, or sometimes even in doses of 1/100 grain twice or three times a day. Ten grains of bromide taken three or four times a day will often answer, though less efficaciously, the same purpose as atropin in allaying nerv- ous irritability, and relaxing the intestinal spasm. "Where gas is extremely troublesome and not relieved by atropin alone, the following prescription, as suggested by Cohnheim, has proved to be of great value in my practice. IJ. Tincturse belladonnas foliorum 5.0-10.0 Spiritus menthaa piperita 5.0 Tinctures valerianic 15.0-20.0 M. Sig.: Thirty drops in a cup of hot carminative tea, three times a day. Since nutrition is such an important factor in the cure of tuberculosis and in the maintaining of health, after once re- gained, it is essential that we should not be satisfied to use laxa- tives to carry our patients along during the time of treatment, but we should help them overcome their constipation when pos- sible. Biliousness (So-called). — While it may be undignified to treat of biliousness in a discussion of this kind, yet I deem it im- portant to emphasize the fact that it is not an entity and that it has no place in our literature. Biliousness is supposed to be an affection of the liver, but, in reality is an acute disturbance in the gastrointestinal tract accompanied by toxemia. It is a group of symptoms, — those of headache, feeling of malaise, lack of desire for work, mental hebetude, sometimes nervousness, vari- able or lack of appetite, coated tongue, and constipation. This might be due to alterations in the gastric or intestinal secretions, to disturbances in motility, or both; or it might be due to some derangement of the important glands associated with diges- tion. I believe the greatest factor is an acute stasis of bowel contents with absorption of toxins. Inasmuch as this condi- tion is usually associated with acute constipation, it is treated with laxatives. In my work I have gradually come to rely 278 DIGESTIVE SYSTEM IN TUBERCULOSIS particularly on one laxative, and that is, castor oil. My in- structions to patients when suffering from this chain of symp- toms is to stop all food or reduce it to a minimum for a day, and take a dose of castor oil. While there is much prejudice against castor oil, I find in my own practice that I am gradually limit- ing myself more and more to its use. It seems to be the most efficacious of any remedy that I have used. It can be made quite pleasant if given in orange juice. Put the juice of half an orange in the bottom of a small medicine glass. Then put in from three-quarters of an ounce to an ounce of oil and cover it over with the juice of the other half of the orange. Let the patient swallow it quickly. It may also be taken in coffee, but I prefer the orange juice. Lemon juice can take the place of orange juice, although it is not quite so pleasant to take. "Where there is great objection to castor oil, saturated solution of epsom salts in half ounce doses may be used, or a teaspoon- ful of saturated solution may be given every hour until a thor- ough movement of the bowels has been obtained. A compound cathartic pill, at night, is also quite valuable. Calomel may be used to advantage. It may be used in small doses of one- tenth grain every hour until a grain has been given, followed either by castor oil or epsom salts ; or, two grains may be given at night, a half grain every half hour until the quantity is taken, to be followed by oil or salts the following morning. The grip- ing caused by calomel may be prevented by the use of some form of hyoscyamus or atropin. In my practice I rarely use any other remedy than castor oil or an enema. These are non-irri- tating and seem to be the least harmful. Nervous Influences in Gastrointestinal Disturbances. — While errors in diet are many and pathological changes in the gastro- intestinal tract not infrequent, yet it is well for both physician and patient to learn that digestive disturbances are just as likely, in fact, more likely to come from within the patient himself and be partially or wholly within his control. Emotional influences, such as those produced by pain, anger, fear and pessimism are exceedingly apt to disturb the gastrointestinal function. While we are constantly looking for mechanical and secretory disturb- ances in the intestinal tracts of our tuberculous patients we must NERVOUS DISTURBANCES OF DIGESTION 279 not forget the very important influence which emotion bears to them and to nutrition in general. If we can keep the patient happy, cheerful, optimistic, hopeful, and free from pain, his di- gestion is better, he sleeps better, and all organs functionate better. On the other hand, if the patient is pessimistic, worry- ing about every little thing that comes up and allowing himself to be depressed and discouraged by trifles, he is apt to have many attacks of indigestion which he could escape by self-control. There is a great deal in the saying, "Laugh and grow fat," because with happiness comes better digestion and better assimila- tion. The effect of emotion on peristalsis is shown by Cannon. 11 He says: "In my earliest observations on the stomach I had difficulty, because in some animals peristalsis was perfectly evident, in others there was no sign of activity. Several weeks passed be- fore I discovered that this difference in response to the presence of food in the stomach was associated with the difference of sex. The male cats were restive and excited on being fastened to the holder, and under these circumstances gastric peristalsis was ab- sent; the female cats, especially if elderly, submitted with calm- ness to the restraint, and in them peristaltic waves took their normal course. Once a female with kittens turned from her state of quiet contentment to one of apparent restless anxiety. The movements of the stomach immediately stopped and only started again after the animal had been petted and began to purr. I later found that by covering the cat's mouth and nose with the fingers until a slight distress of breathing occurred the stomach movements could be stopped at will. Thus, in the cat, any sign of rage, or distress, or mere anxiety, was accompanied by a total cessation of the movements of the stomach. I have watched with the x-rays the stomach of the male cat for more than an hour, during which time there was not the slightest beginning of peristaltic activity, and yet the only visible indication of ex- citement in the animal was a continued to-and-fro twitching of the tail. ' * \m { p§ ^ "What is true of the cat has been proved true also of the rab- u The Mechanical Factors of Digestion, Longmans, Green & Co., New York, 1911. 280 DIGESTIVE SYSTEM IN TUBERCULOSIS bit, dog, and guinea pig. A female cat that ordinarily lies quietly in the holder, and makes no demonstration will occa- sionally, with only a little premonitory restlessness, suddenly fly into a rage, lashing her tail from side to side, pulling and jerk- ing with every limb, and biting at everything near her head. During such excitement and for some moments after the animal has become pacified again, the movements of both the large and small intestines entirely cease. The opposing influences, reach- ing the alimentary canal by way of the sympathetic system dur- ing emotional excitement, can wholly destroy both the secretory and motor activities which have been started by the bulbar system. The importance of avoiding so far as possible the states of worry and anxiety, and of not permitting grief and anger and other violent emotions, to prevail unduly, is not commonly appreciated; for the subtle alterations wrought by these emotional disturbances are uncommon to consciousness and have become clearly demonstrated solely through physio- logical studies. Only as the consequences of mental states favor- able and unfavorable to normal digestion are better understood can good results be sought and bad results avoided, or, if not avoided, regarded and treated with intelligence." Amyloid Degeneration. — In advanced tuberculosis the vessels of the intestinal tract often become the seat of amyloid de- generation. This causes the interference with secretion, motility, and absorption, and is especially serious because it cannot be remedied. Errors in Diet. — Errors in diet should be avoided as much as possible where a high state of nutrition is desirable. Errors in diet may be due to the eating of the Avrong kind of food, or to eating too much or too little food, or to eating food which is not suited to the nutritive requirements of the patient or the peculiar digestive conditions present. CHAPTER XI. COMPENSATORY CHANGES IN THE THORACIC AND ABDOMINAL CAVITIES RESULTING FROM PULMONARY TUBERCULOSIS. When we consider the compensatory changes which take place in pulmonary tuberculosis, particularly in the advanced disease, we are forced to see clearly that while this is primarily a disease of the lung, it is accompanied by secondary changes which affect every organ in the thoracic and abdominal cavities. These compensatory changes must be discussed together. They are so intimately related that it is impossible to completely sepa- rate those which take place between the organs within the chest itself from those which take place between the organs of the abdominal and thoracic cavities. This can be understood by con- sidering the thoracic and abdominal cavities as one large cavity with a flexible partition separating them. No increase of tissue or loss of tissue can occur in one part of this cavity without af- fecting all parts ; neither can any increase or decrease in the con- tour of the walls take place in any one portion of this cavity without affecting other or all portions. The symptoms which are produced as a result of the disturbed function of the organs and parts which take part in the produc- tion of compensation are such as might be caused by other condi- tions present as well; consequently, the reader must bear in mind that while the symptoms mentioned may be caused by the conditions under discussion, they are not, necessarily, wholly due to them. It is often impossible to assign the true cause to each symptom because several conditions all of which are pres- ent, are capable of producing it. So, in reading this chapter, let it be borne in mind that the symptoms here mentioned may be caused by many conditions, among which are the shifting of or- gans and resulting compensatory changes described. Compensatory Changes Taking Place Within the Thoracic 282 COMPENSATORY CHANGES IN TUBERCULOSIS Cavity. — In order to understand the extent of compensatory- change which takes place between the organs within the thorax in pulmonary tuberculosis, it is necessary to consider the thoracic cavity as a cone-shaped cavity whose walls on all sides, except the base which is a thin flexible membrane, are made up of a framework of bones. All of these walls, even the bony ones, are somewhat yielding to pressure but they maintain their position and shape under conditions of health, and, as a rule, change their contour only when the organs within, or adjacent, are affected by pathological changes. Changes in the contour of the flexible membranous wall (diaphragm) occur and will be discussed fully later on; but it is necessary to state at this time that the posi- tion of the diaphragm is a peculiarly sensitive one. It depends upon the relative pressures in the thoracic and abdominal cav- ities. Normally, the pressure in the thoracic cavity is negative while that of the abdominal cavity is positive. The negative pressure of the thoracic cavity tends to draw or suck the dia- phragm upward, while the positive pressure of the abdominal cavity tends to push it upward and hold it there. The thoracic cavity is divided by the structures of the mediastinum into a right and left portion. These dividing struc- tures are movable. They shift from one side to the other as con- ditions demand. They respond to any increase and decrease of substance or pressure in either the lung or pleura by shifting their position. In this connection the compensatory character of lung tissue must also be considered. The lung is subject to many pathological conditions in some of which there is a loss of tissue either confined to some small area or affecting a large area; in others the air cells dilate and the lung enlarges, either in circumscribed areas or generally. As a rule, the loss of tis- sue is compensated for, as far as possible, by enlargement of other portions of the lung or lungs (compensatory emphysema). These compensatory changes are unavoidable ; in fact, they are very desirable under the circumstances; yet they are abnormal conditions which are, according to their extent, productive of symptoms of greater or lesser severity. To appreciate the compensatory changes which take place be- tween the two sides of the thorax a correct conception of the NATURE OP MEDIASTINUM 283 mediastinum must be had. The mediastinum may be likened to a swinging door in the center of the thoracic cavity. It swings back and forth to either side as necessity demands. It is hinged to the posterior wall by the arteries and veins which pass be- tween the large blood vessels and the intercostal structures. The anterior portion is fastened to the under surface of the sternum by the pericardium, — a structure which varies in size, it being usually large, and, in some instances, excessively large, permits of considerable freedom in the motion of the anterior portion of the door (to carry out the figure) ; consequently a contraction of the tissues on one side, with compensatory enlargement on the other, permits the door to swing toward the side of contraction. The extent of its motion is limited only by the size of the peri- cardium and the amount of play that it will permit. In discussing this subject in a former paper, 1 the writer said: "It is somewhat surprising that these conditions have not re- ceived more attention from clinicians when we consider the fact that they are present and produce symptoms in nearly all patients who are suffering from tuberculosis. There are displacements of the heart in some form and to some degree in practically all cases where either a lessening or increase in the volume of the lung occurs. The function of the diaphragm is interfered with from the very beginning of tuberculosis. It is displaced either upwards or downwards in nearly all patients who go on to an advanced stage of the disease, the dislocation depending upon the relationship between the intra-abdominal and intrathoracic pressures. "The symptoms which result from these conditions can only be understood in connection with the physiology of the heart and diaphragm. The heart is normally placed in the thoracic cav- ity in a position which enables it to perform its function with ease. The circulation of the blood is aided by every normal respiration. Any condition which changes the position of the heart, putting it in a position less favorable to action, and any condition which interferes with the full and free respiratory iDisplacements of the Heart and Diaphragm, Together With Disturbances in the Func- tion of the Latter as Causes of Symptoms in Pulmonary Tuberculosis, Interstate Medical Journal, vol. xviii, No. 6, 1911. 284 COMPENSATORY CHANGES IN TUBERCULOSIS movements, therefore, interferes with the circulation of the blood." Aside from the symptoms due to abnormal conditions in the heart and diaphragm there are many which are due to the changes in the lung. When ulceration, fibrosis, or both combined, are sufficiently ex- tensive to call for a compensatory emphysema, the respiratory function is more or less interfered with and circulatory disturb- ances make their appearance. The thorax is a closed cavity in which a negative pressure ex- ists, and at every physiological enlargement of this cavity, such as occurs during inspiration, the air in the bronchi and air cells attempts with all the pressure of the atmosphere back of it, to fill in the enlarged space. Likewise with every pathological diminution of pulmonary tissue such as occurs in tuberculosis when destruction of tissue takes place, the pressure in the re- maining portions of the air chambers is relatively decreased. The result in these pathological conditions where the pulmonary tis- sue has wasted to any extent, is that the thin-walled air cells of the remaining portion of the lung yield to the atmospheric pres- sure, dilate and produce an enlargement of that portion of the lung involved (compensatory emphysema). An equilibrium between the intrathoracic and intra-abdominal pressures on the one hand and between these and the atmospheric pressure on the other hand, both as it surrounds the surface of the body and as it fills the air chambers of the lung, must be maintained under all circumstances if the proper functionating capacity of the various organs in these cavities is to be main- tained. To the extent to which pulmonary tuberculosis disturbs this equilibrium without full compensation; and to the extent to which the compensatory changes which occur, take place to the disadvantage of the various functionating powers of the organs concerned, is the disease responsible for the pathological changes and untoward symptoms. Of the many pathological changes which take place in the lungs and pleura, some cause so little change in tissue that their effect on the mediastinum and diaphragm is negligible; but any COMPENSATORY CHANGES IN LUNG 285 considerable loss of lung tissue, or any marked decrease in the respiratory function in one part of the lung, is followed by a compensatory increase in other parts. Man is naturally endowed with an excess of lung tissue over what is actually needed for the ordinary acts of life. This en- ables him to respond to unusual effort and strain by calling his reserve lung power into action. It has been estimated that a man can exist on about one-twelfth of his lung area; be fairly active on one-half and perform most of the ordinary acts of life without strain, on two-thirds. A person who has lost one-third of his pulmonary area, however, would not be able to measure up to any marked sudden effort or strain, for he has no reserve lung area to call into action. In nature 's attempts to compensate for loss of tissue, she some- times defeats her purpose by producing conditions which by them- selves are deleterious. Thus, at times, such a degree of compensa- tory emphysema is produced in advanced destructive tubercu- lous lesions that this of itself proves to be harmful to the pa- tient, by the reduced functionating capacity of the lung tissue involved, and by the extra burden thrown on the heart as a re- sult of it. When an extensive degree of emphysema is present the heart is less able to cope with the extra work too, because it has been subjected to more or less degenerative change owing to the destructive process in the lung and the general malnutri- tion and because it is forced out of its natural position to the right or to the left and is working at a disadvantage on this ac- count. Shifting of Mediastinum. — The shifting of the mediastinum to a recognizable degree is extremely common in advanced tuber- culosis. The amount of this shifting depends on a number of factors. The mediastinum, as a whole, shifts to the left easier than to the right. The anterior mediastinum shifts easier than the posterior because the aorta in the posterior mediastinum is held fairly firmly in its position by the intercostal branches which it gives off to pass into the structures on either side of the verte- bral column. The large vessels are also fixed to a certain extent by the large branches which pass up into the neck. The heart, on the other hand, which fills the anterior mediastinum in its low- 286 COMPENSATORY CHANGES IN TUBERCULOSIS er portion, is contained in the pericardium, a sac varying much in size, and allowing of considerable movement on the part of the heart lying within. The amount of movement which the heart can make in health and the ease as well as the extent to which the heart moves under pathological conditions depends largely upon the size of the pericardium. While the structures in the upper portion of the mediastinum do not shift their posi- tion readily, yet they offer so little resistance that the enlarged lung on the side opposite the destruction may gradually force its way between it and the anterior surface of the chest wall over to the other side of the median line. In one of my cases (Fig. 40) the left lung had formed a new lobe which had forced its way three inches beyond the median line to the right. The pericardium is attached anteriorly to the under surface of the sternum, inferiorly to the diaphragm, superiorly to the great vessels, and laterally to the right and left pleura. In advanced tuberculosis, the inferior and two lateral attach- ments are unstable and subject to considerable change in posi- tion, thus allowing the heart to shift its position. Displacement of the Heart. — In my practice I have found severe destructive changes of wide extent to be most common in the left lung, the upper lobe being involved, as a rule, more exten- sively than the lower; although large cavities and extensive fibrosis are often formed in the lower lobe also. The right lung is severely diseased less often; but when it is, the conditions duplicate those in the left, the upper portion showing the more extensive process. That the upper lobe should be the seat of the more extensive involvement is evident from the fact that the primary pulmonary infection is usually near the apex whether it be the first apex involved or the extension to the other lung ; and, the disease spreads downward contiguously from the original metastasis. From this fact it is also evident that the greatest evidence of healing with the formation of fibrous tissue should be found in the upper lobes where the lesion is oldest and where the process was present before the patient's recuperative powers were so severely taxed. "While we often find extensive healing in the lower lobes, yet, being, as a rule, a later infection, heal- -. E C . p 1 Fig. 40. — Illustrating the distortion of the thoracic viscera in a patient with a marked destructive lesion in the right lung, and marked compensatory changes in the left. A, the upper lobe on the right, is a small fibroid mass; B, the middle lobe, is only a fibrous string; C, the lower lobe, barely presents anteriorly, but posteriorly, was the seat of emphysema; D, three-fourths of the heart lies to the right of the median line; E, the upper lobe on the left represents a large portion of the lung which presents anteriorly. A new lobe has been formed, pushing through the anterior mediastinum to a distance of three inches beyond the median line; F, the lower lobe is also markedly emphysematous; G, trachea. DISPLACEMENT OP HEART 287 ing does not take place as extensively here as in the upper lobes. The direct factors which cause the heart to change its posi- tion are the loss of lung tissue and coincident compensatory en- largement of other portions. In the final analysis, however, it is due to the necessity of maintaining a definite pressure equilibrium between the air containing chambers within the lung and the at- mospheric air surrounding the outer chest wall. The bony cage yields some, but cannot make up for the entire deficiency ; neither would we expect it to yield except after all more pliable struc- tures had yielded to their full extent, unless the contraction of the muscles was a factor. The diaphragm pushes upward, but this too is, limited in its ability to satisfy the demand, so it must be met by the tissues within the thorax itself. The pleural sac remains closed because of its negative pressure, or it may be obliterated because of adhesions; consequently the only method of meeting the demand which cannot be met by the diminishing of the size of the bony cage, and by the ascent of the diaphragm, is by enlarging (compensatory emphysema) that portion of the lung which is not destroyed by ulceration and fibrosis. Such changes disturb the nicely balanced symmetry which ex- ists normally between the two sides of the thoracic cavity and between it and the abdominal cavity and cause a distortion of all the structures within the thoracic cage. The amount of dis- tortion is determined by the amount of destruction in the pul- monary tissue, the degree of compensatory emphysema, and the size of the pericardium and the amount of displacement which it will permit the heart to undergo. The entire mediastinum is disturbed in its relationship but the heart is the organ that shows the greatest displacement. These displacements vary according to the character of the changes in the lung. In this present discussion I am omitting considera- tion of those acute displacements which occur as a result of changes in the pleura. I have noted the following relationship between displacements of the heart and the pulmonary involvement. 1. If there is a small lesion in one or both lungs, there is no appreciable change in the position of the heart. 2. If the lesion becomes more extensive and heals there is a 288 COMPENSATORY CHANGES IN TUBERCULOSIS tendency to draw the borders of the lung upward, and with them the pericardium. This is counteracted, however, as a rule, by a compensatory emphysema developing which affects the lower portion of the lungs and holds the diaphragm somewhere near its normal position or even pushes it lower. I have seen a few hearts that seemed to be raised in toto because of such a double lesion. The effect of such a change in position is to shorten the distance between the apex and the large vessels, thus producing a tendency to pouch the aorta. 3. At times, when a double involvement exists at the apices, the opposite occurs. A high grade of compensatory emphysema develops pushing the diaphragm downward. The heart follows the diaphragm and hangs suspended from the great vessels the same as it does in those enteroptotic individuals who are occa- sionally seen who suffer from suspensio cordis. I have seen sev- eral cases such as these. When examined by the fluoroscope during inspiration, as the diaphragm sinks, the heart, being unable to follow, hangs suspended, dragging on the aorta. Such is the case in many patients of the asthenic type. 4. The most common extensive displacement as mentioned above, is the one when the heart is displaced to the left and upwards (Fig. 41). In advanced tuberculosis a degenerative process which goes on to the destruction of the greater portion of the upper left lobe is not uncommon. A portion of the lower lobe is usually destroyed at the same time. Such a condition may occur and yet, the patient, if properly treated, obtain an arrestment of his disease and regain fairly good health. If an arrestment takes place it is accompanied by the formation of fibrous tissue and contraction. The walls of the cavity or cavities are compressed and the lung area which was involved in the severe destructive process is greatly reduced in size. At times a very marked contraction occurs, even though it was not pre- ceded by a destructive process with cavity formation, the process from the start being one accompanied by the formation of fibrous tissue. Under such circumstances compensation takes place, not only in the lower portions of the left lung, but also in the right lung. Equilibrium can only be established when the space in the thorax occupied by that portion of the destroyed and con- DISPLACEMENT OP HEART 289 tracted left lung is occupied by other tissue. To this end, the right lung enlarges under the pressure of the atmosphere and gradually pushes over against the mediastinum, forcing the heart, which is also being pulled by the contracting lung, over toward the left. The diaphragm pushes up at the same time from below and this forces the apex of the displaced heart up- . Fig. 41. — Illustrating schematically the displacement of the heart to the left. It will be seen that the left half of the diaphragm is pushed upward, and the apex of the heart follows the fifth interspace. This displacement has a tendency to reduce the curve in the arch of the aorta. The trachea may be drawn entirely to the left of the median line as shown in the cut. wards, the two forces together pushing it to the left and up- ward. This displacement is often so great that the entire heart is to the left of the sternum. This displacement not only causes the heart to be thrown out of its normal position and work at a disadvantage because of 290 COMPENSATORY CHANGES IN TUBERCULOSIS this ; but the pericardium still maintaining its attachments to the sternum and center of the diaphragm is unquestionably pushed so far from its moorings that its surfaces are brought into con- tact in such a manner that it materially reduces the pericardial space. This altered position of the heart causes marked dragging on Fig. 42. — Illustrating schematically marked displacement of the heart to the right. It will be noticed that the heart is pushed upward and over. The right side of the diaphragm assumes a high position; while the left side assumes a low one in order to accommodate the left lung which is the seat of compensatory emphysema. When this displacement is present, the curve in the arch of the aorta is lessened with a tendency to pouching. the great vessels at its base, decreasing the curve of the arch of the aorta, thus bringing about a condition which interferes with the free flow of blood into the systemic arteries. The same dragging force exerts a pull upon the other ves- DISPLACEMENT OP HEART 291 sels at the base of the heart, drawing the pulmonary artery and large veins out of their normal course and interfering with the outflow of blood from the right ventricle and the return flow to the auricles. Dragging on the trachea often provokes cough. 5. If the severe destruction occurs in the right lung, instead of the left, the heart is displaced upwards and to the right as shown in Fig. 42. When the destruction and contraction are very marked, the heart may be displaced entirely to the right of the sternum, but this is rare compared with the total displace- ment to the left. This displacement is not as natural as that toward the left. The heart lies on the diaphragm in such a way that it can be pushed to the left with ease, but, when pushed to the right, its apex meets the obstruction of the central portion of the di- aphragm and the underlying liver. And, too, the diaphragm and liver are pushing up into the thoracic space at the same time, in order to help compensate for the loss of tissue. The result is that the heart as a whole is lifted as well as pushed over to the right. The effect of such a new position is to push up and widen the arch of the aorta. This creates a relaxed condition, with a ten- dency to pouching. The distortion of the other vessels is also marked and, the free flow of blood to and from the heart is impeded. The same constriction of the pericardial space ensues as above described and the heart is forced to work in a position even more unfavorable than that mentioned above. Not only is it more difficult for this displacement to take place, but in my experience, it proves more embarrassing to the heart which gives out more quickly under it. As a result of these marked compensatory displacements in the thorax, the trachea is drawn or pushed over toward the side which is the seat of the destructive process. This can usually be determined by noting the position of the larynx and following the direction of the trachea as it passes down to enter the thorax. It is a suggestive point in the diagnosis of this condi- tion. 292 COMPENSATORY CHANGES IN TUBERCULOSIS In these displacements the recurrent laryngeal nerve is often disturbed, a brassy cough resulting similar to that which is often described in aneurysm. At times there is also noted a marked difference in the blood pressure in the two arms which might also add to the suspicion of aneurism. Effect of Displacements of Heart. — To understand the full sig- nificance of these displacements and their effect upon the heart, we must discuss other factors than those just mentioned which have a tendency to embarrass the heart's action. Among such are the pleural adhesions which are nearly always present; the displaced diaphragm with its consequent disturbed function which will be discussed later in this chapter; the resistance offered in the pulmonary circulation by the destruction of vessels in the contracted areas as well as the embarrassment imposed by the emphysematous areas; the thickening of the arteries which re- sults from the tuberculous infection, 2 and the degenerations of the heart muscle which result from the action of the specific bacil- lary and other toxins as well as the malnutrition present. The heart is called upon to carry an enormously increased load; at the same time its muscle is weakened, and it is forced to work under disadvantageous conditions. The cause of death in these cases of severe destruction and marked displacement is nearly always degeneration and dila- tation. The patients live as long as their hearts will permit them to live. The symptoms which occur during the time that the heart is changing its position depend on the rapidity with which such change takes place. In some cases we see the displacement take place rapidly as in the case mentioned in one of my former papers, 3 but, as a rule, several months are occupied in shifting the position. Since the diaphragm is disturbed in its function and since there is evidence of activity in the pulmonary tissue at the same time, it is extremely difficult to sepa- rate the symptoms which belong to the one condition from those that belong to the other. From the nature of the case they 2 Pottenger: The Effect of Tuberculosis on the Heart, Archives of Internal Medicine, vol. iv, 1909. displacements of the Heart and Diaphragm Together With Disturbances in the Func- tion of the L,atter as Causes of Symptoms in Pulmonary Tuberculosis, Interstate Medical Journal, 1911, vol. xviii, no. 6. EFFECT OF DISPLACEMENT OF HEART 293 would be those which belong to the group of cardioneurotic symptoms such as weakness, lack of endurance, slight dyspnea, dizziness, faintness, disturbed appetite, nausea, and increased pulse rate. When these changes are occurring the patient can be kept comfortable by remaining at rest as all of the symptoms are increased on exertion. Low blood pressure is probably an important etiological factor in this chain of symptoms. Displacements of the mediastinum should be looked for in every case of advanced tuberculosis which has suffered the loss of tissue to any extent. The condition will often suggest itself to the alert examiner when he inspects the chest, for one side with its narrow interspaces will be small, suggesting contraction, and the other large and bulging with wide intercostal spaces, sug- gesting emphysema. The heart impulse is often visible and shows either to the right or left of the normal place for the apex. This impulse must not be taken as the apex. Very often it is pro- duced by the right ventricle instead. Palpation or percussion will usually show the deep borders of the heart displaced and examination of the larynx and trachea will show that they are drawing toward the side of contraction as mentioned above. The second pulmonary sound is usually markedly accentuated be- cause of the increased intrapulmonary pressure and also because the valve is uncovered when the contraction is on the left. The second aortic sound is also often increased. But, on the other hand, the sounds may be weaker than normal when the shifting is occurring, owing to the weakened condition of the heart muscle at the time. Compensatory Changes in Thoracic Cage. — A discussion of this subject would not be complete without mentioning the part taken in compensatory changes by the bony framework of the thorax. Changes in contour of the thoracic cage are extremely common. Contraction occurs in one portion, expansion in an- other, and flattening is sometimes more or less general. All of these changes must be looked upon as a part of the one ever present scheme of maintaining an equilibrium between the air pressure without the body and that within the air chambers of the lungs. If the contractions which take place in the bony cage are 294 COMPENSATORY CHANGES IN TUBERCULOSIS purely passive in character, then we -would not expect them to occur except as a last resort, after the structures within the thorax and abdominal cavities had been unable to make up for the tissue lost. Given a movable mediastinum which presumes a large non-adherent pericardium, permitting of easy and wide movement of the heart; a lung fairly free from disease on the other side, capable of taking upon itself a high degree of com- pensatory emphysema ; and a diaphragm capable of moving, we would not expect any passive contractions of the chest wall until these soft movable tissues had exhausted their capabilities of compensation, or, in other words, until the force necessary to compensate affected the bony framework rather than the usually more movable soft tissues. It must be borne in mind, however, that the action of the ribs on the affected side is not normal, not from the time the early infection of the pulmonary parenchyma takes place. There is a shortening of the respiratory muscles which are renexly thrown into contraction. There is a decrease in the elasticity of the lung tissue, and a general limiting of the inspiratory act due to the fact that many of the inspiratory muscles, including the di- aphragm, have their respiratory function renexly disturbed. As a result, the side of the chest affected, does not take its nor- mal part in the inspiratory act and it becomes relatively some- what smaller than the other side. It seems but natural that the contraction of the muscles, which exists for a prolonged time, should exert an active force in producing a certain amount of compression of the bony cage. 4 Study of the mechanics of respiration emphasizes this. When we see local contractions in one portion of the bony cage and enlargements in another, particularly when the con- traction is confined to the ribs over one lung and the enlarge- ment to those over the other, we must assume that certain ob- stacles have been met, and certain difficulties in establishing equilibrium by means of the intrathoracic and intra-abdominal structures have presented themselves which could not be over- come, and that the bony cage has been forced into the com- 4 Pottenger: Muscle Spasm and Degeneration in Intrathoracic Inflammations and Light Touch Palpation, C. V. Mosby Company, St. Louis, 1912. COMPENSATORY CHANGES IN BONY THORAX 295 pensatory scheme as being the structure most yielding at this time. Such a condition aside from the changes which result from muscular contractions, to my mind, could only exist when all compensation possible had taken place between the thorax and abdominal cavities and when there was an obstruction to the further shifting of the mediastinum. Therefore, it would seem probable that in such cases the heart had pushed over as far as its pericardium would allow it to push; and that the enlarged lung was still being enlarged by the atmospheric pressure, and not being able to move further toward its fellow, and likewise meeting obstacles from below the diaphragm, expended its crowding force against the ribs which at the time offered the least resistance. The principle that all bodies move in the direc- tion of least resistance applies here, so we cannot expect an en- largement of the bony thorax until such a time as this enlarge- ment takes place easier than enlargement in other directions. In speaking of the bony cage being resistant, this must be un- derstood as being in a relative sense only. We recognize that the contraction and enlargement that occurs takes place by de- pressing and lifting the ribs on their articulations, by changing the angle of articulation. COMPENSATORY CHANGES TAKING PLACE BETWEEN THE THORACIC AND ABDOMINAL CAVITIES IN PULMONARY TUBERCULOSIS. This subject has received but scant attention as yet in medi- cal literature; but it is one that demands more consideration, if we are to understand the circulatory changes which affect the tuberculous patient in any stage of the disease, but particu- larly the one suffering from the advanced stage. As the compensatory changes in the thoracic cavity show in displacements of the mediastinum, particularly the heart, so the compensatory changes between the thoracic and abdominal cav- ity show in displacements of the diaphragm. The Inspiratory Act. — In order to understand the displace- ments of the diaphragm it is important to study the function 296 COMPENSATORY CHANGES IN TUBERCULOSIS of this important muscle and its relationship to the other mus- cles of respiration. I would refer those who may be interested, to the writings of Hasse, 5 Keith, 6 Wenckebach, 7 and Eppinger. 8 The diaphragm must be looked upon as being the chief muscle of respiration and, as such, it has a very pronounced effect upon the circulation; for the flow of blood toward the heart, and in- directly the entire circulation, is greatly influenced by the phases of respiration. Its position differs according to the age of the patient, as shown in Figs. 54, 55, and 56, Chapter XIII. Inspiration is a muscular act and takes place through contrac- tion and sinking of the central tendon of the diaphragm innervated by the phrenics and a simultaneous lifting of the ribs. The lifting of the ribs, in quiet breathing, is brought about by contraction of the intercostales externi, the intercostales interni and the intercar- tilaginei, supplied by the intercostal nerves and the levatores cos- tarum supplied by branches from the dorsal nerves. The lifting of the ribs in forced inspiration is aided by the accessory muscles of respiration. These are : 1. The three scaleni innervated by branches from the cervical and brachial plexuses. 2. Serratus posticus superior, innervated by the dorsalis scapula? from the fifth cervical. 3. Sternocleidomastoideus innervated by the accessorius and branches from the second and third cervical nerves. 4. Trapezius innervated by the accessorius and branches from the third and fourth cervical nerves. 5. Rhomboidei innervated by the dorsalis scapulas. 6. The extensores columnse vertebrales innervated by the posterior branches of the spinal nerves. 7. Pectoralis minor innervated by branches from the anterior thoracic nerves. Conditions which interfere with the action of the diaphragm or the first group of muscles mentioned will interfere with the normal quiet respiratory act; likewise conditions which inter- B Die Atmung und der venose Blutstrom, Archiv fur Anatomie und Physiologie, Abt., 1906. 6 Further Advances in Physiology, Hill, London, 1909. "Uber pathplogische Beziehungen zwischen Atmung und Krieislauf beim Menchen, Sammlung Klinischer Vortrage (Volkmann) Innere Medizin, No. 140 and 141, 1907. 8 Allgemeine und Spezielle Pathologie des Zwerchfells, Alfred Holder, Wien und Leip- zig, 1911. THE INSPIRATORY ACT 297 fere with, the diaphragm and the second group of muscles men- tioned will interfere with forced respiration. Increased tone (spasm) or degeneration of these various muscles, by which their action is altered, such as is present in tuberculosis, or displace- ment of the diaphragm which is so common in advanced tuber- ^ Fig. 43. — Showing the movements of the diaphragm and thoracic and abdominal walls as well as the change in position of the intrathoracic and intra-abdominal viscera during respiration of the thoracic type. The movements are from the solid lines on expiration to the broken lines on inspiration. (Hasse.) culosis interferes with inspiration and indirectly exercises a del- eterious effect upon the flow of blood to and from the heart. The influence of respiration upon the circulation may be under- stood by studying the changes which occur in the thoracic and 298 COMPENSATORY CHANGES IN TUBERCULOSIS abdominal cavities during the act of breathing. These can be seen by studying the accompanying figures after Hasse. Fig. 43 illustrates normal breathing of the thoracic type. The move- ments of the various structures and organs are from the position Fig. 44. — Illustrating the movements of the diaphragm and thoracic and abdominal walls as well as the change in position of the intrathoracic and intra-abdominal viscera during respiration of the abdominal type. The movements are from the solid lines on expiration to the broken lines on inspiration. (Hasse.) of the solid lines on expiration to that of the broken lines on inspiration. The entire chest wall anteriorly and posteriorly is carried forward, the diaphragm is shortened in its anteroposterior diameter and the sternum is raised and pushed forward. Fig. TYPES OF RESPIRATION 299 44 represents the diaphragmatic type of breathing. The walls of the chest are not moved to any great degree, but the diaphragm pushes downward and the anterior and lateral walls of the ab- domen are pushed outward. In its downward action the di- Fig. 45. — Showing the movements of the diaphragm and thoracic and abdominal walls as well as the change in position of the intrathoracic and intra-abdominal viscera when combined thoracic and abdo*minal breathing are pronounced. The movements are from the solid lines on expiration to the broken lines of inspiration. (Hasse.) aphragm compresses and squeezes the abdominal viscera and in this way forces the blood from the intra-abdominal organs. This effect is all the more important because the thoracic cavity is being enlarged at the same time as the compressing force is being 300 COMPENSATORY CHANGES IN TUBERCULOSIS exerted. Fig. 45 illustrates the type of combined thoracic and diaphragmatic breathing in which the compressing abdominal force is more than in the thoracic but less than in the diaphrag- matic type. The importance of the diaphragm as a muscle of respiration may be inferred from Fig. 46, which represents a sagittal sec- -Q.YUS Fig. 46. — Sagittal section of the body showing the relationship of the diaphragm to the pericardium, particularly showing the importance of the crus, with its attachment to the low lumbar vertebrse, the contraction of which markedly enlarges the entire thoracic space. The crus is the portion which secures its innervation from the cervical segments of the spinal cord. (Wenckebach.) tion through the body made in such a manner as to show the crus with its attachments to the lumbar vertebrse. Contraction of this portion of the diaphragm exerts a very marked force on the abdominal contents. When the diaphragm contracts the intra- abdominal pressure is increased and the abdominal muscles are INSPIRATORY ACT AND CIRCULATION 301 pushed outward carrying the lower central arch with them, and at the same time other muscles of inspiration contract and raise the ribs. The result of this action is shown in Fig. 47. The effect of lessening the diaphragmatic action is shown in Fig. 60, A and B, page 328. In A we see that as the diaphragm contracts the lower ribs are forced outward and the intrathoracic space is enlarged. In B we have the motion of the left half of the diaphragm lessened with a resultant decrease in the normal inspiratory enlargement of the left side of the chest. This con- dition is frequently met with in pulmonary tuberculosis both as a result of reflex action through the phrenics and as a result of inflammation of the pleura. Fig. 47. — Illustrating the movement of the ribs and sternum during inspiration. Inspiratory Act and Circulation. — One of the most important factors in the circulation of the blood, outside of the heart's ac- tion itself and the elasticity of the vessel walls, is the suction ex- erted upon the blood column by the thoracic cavity during respiration. The part of the diaphragm in this act can be ap- preciated from the following from Wenckebach : 9 ' ' The diaphragm "Uber pathologische Beziehungen zwischen Atmung und Krieislauf beim Menchen. Sammlung klini'scher Vortrage (Volkmann) Innere Medizin, No. 140 and 141, 1907. 302 COMPENSATORY CHANGES IN TUBERCULOSIS of mammals is the most important factor in the filling of the heart, while in amphibians and the lower vertebrates it is the only factor." The pressure within the thoracic cavity outside of the air pas- sages is negative and decreased with every inspiration. The di- aphragm contracts forcing the abdominal viscera downward and the lower border of the ribs outward both anteriorly and later- ally, the other muscles of inspiration contract simultaneously and lift the ribs, at the same time increasing both the antero- posterior and lateral diameters of the chest! The result in nor- mal respiration is a very marked increase in the intrathoracic space, causing a markedly negative pressure and dilatation of the large veins and chambers of the heart. During the entire act of inspiration the blood is being sucked in to fill these veins. With every expiration, on the other hand, the negative pressure dimin- ishes, the veins and auricles become less distended and the return flow of blood into the thorax is impeded. The intrathoracic pres- sure is decreased in direct proportion to the depth of the inspira- tion, consequently the favorable influence upon circulation likewise varies with the depth of the inspiration. Conditions which in- crease intrathoracic pressure embarrass the heart and may prove serious. The following are the three chief factors concerned in the dis- placement of, and disturbance in the function of, the diaphragm in tuberculosis; the reflex stimulation with consequent change in tone from the inflammation in the lung, not only of the diaphragm itself through the phrenics but of the other muscles of inspira- tion through their respective nerves; the loss of tissue and con- traction and compensatory emphysema which occurs in the lung, and the alteration of the intra-abdominal pressure due to the wasting of the intra-abdominal organs and the abdominal mus- cles. These factors operating either singly or jointly, as they frequently do in tuberculosis, will cause disturbance in the cir- culation. Not only is an aspirating effect normally exerted upon the blood, sucking it into the thoracic cavity and heart, but, as the diaphragm contracts it increases the intra-abdominal pressure and exercises a compressing force upon the contents of the ab- SYMPTOMS DUE TO DEFICIENT INSPIRATORY ACT 303 dominal cavity and actively squeezes the blood out of the organs. A disturbance in the action of the diaphragm and the accom- panying embarrassment of the act of inspiration then has a very deleterious effect. Failing to pump the blood into the heart in its normal amount, the heart must accommodate itself to a rela- tively small amount of blood; also to delivering smaller amounts of blood at each systole, the result of which is : 1. A decrease in the actual size of the heart. 2. A relatively smaller amount of blood in the arteries than normal, thus producing a relative arterial anemia. 3. A decrease in blood pressure, and 4. A storing up of blood in the venous reservoirs of the body, particularly the liver, vena cava inferior and splanchnic veins. The small heart has long been described as being a predis- posing factor in tuberculosis ; but it seems to me to be accounted for far more satisfactorily in this natural way. Symptoms Following Deficient Inspiratory Act. — As a result of the storing up of the blood in the liver and splanchnic veins we have many of the digestive disturbances which are so common in tuberculosis. This congestion interferes with the function of the organs. It causes the secretions to be altered, disturbs motility, favors intestinal stasis, gas formation, and colitis; and, by retarding the blood and lymph movements, favors metastatic infection. It also interferes with the general metabolic activities throughout the body. As a result of the various conditions which are produced by the disturbance of the function of the diaphragm, there is a cer- tain chain of signs and symptoms which manifest themselves, most of which are of the cardioneurotic type. These patients look pale, yet, if the blood is examined, the ex- pected change in its constituents may not be found. This is par- ticularly characteristic of the tuberculous patient, even early in the disease. "While we must admit that anemia can and does oc- cur in early tuberculosis, and is often an accompaniment of late tuberculosis, and that tuberculosis develops in anemic individuals; yet there is a paleness common, even in the early stages as well as the late stages, which is accompanied by little or no change in the blood picture. This is accounted for by the relative arterial 304 COMPENSATORY CHANGES IN TUBERCULOSIS anemia which, results from the reflexly disturbed action of the diaphragm and the other muscles of inspiration, producing an embarrassment of the inspiratory act and a consequent lessening of the amount of blood sucked into the heart and a diminution of the amount delivered into the arteries at each systole. The sys- temic arteries being relatively empty, the patient appears pale. The same condition accounts for the small pulse and low blood pressure and is another factor which tends to increase the heart's action. Shortness of breath, lack of endurance, dizziness, faint- ness, palpitation and coldness of the extremities are often com- plained of. Disturbance in function on the part of the abdom- inal viscera, such as altered secretions, disturbed motility, colitis, flatulence, diarrhea and constipation are very common. One thing particularly characteristic of the abdominal com- plications just mentioned in tuberculosis is that they are more persistent and yield less readily to treatment. This is probably due in part, at least, in the advanced disease, to degenerations present but also to the constant congestion of the abdominal or- gans. An unstable nervous system is another condition which may be traced to this cause, while there is some degree of neurasthenia in nearly all tuberculous patients, yet I have noted that there is an unusual instability often present where the diaphragmatic disturbance is marked. Especially is this noted during the time when the disturbance is acute. It is remarkable, however, to see how well nature can compensate for these disturbances. With patience and encouragement during the time when the destruc- tive process is going on in the lung and the compensatory changes are taking place, the patient will usually arrive at a place where there is no more shifting of the position of the organs and then a remarkable degree of stability will be acquired and the trouble- some symptoms will disappear. In order to comprehend the great importance of the inspiratory act in aiding the circulation of the blood in man, and to fully grasp the part played by the diaphragm it is but necessary to study the effect of the upright position in animals. It has been shown by physiologists that small animals like the rabbit and guinea pig held in the upright position for a period of time, are DISTURBANCES IN POSITION AND FUNCTION OF DIAPHRAGM 305 unable to maintain their circulation; and die of arterial anemia. Man, on the other hand, with his well developed diaphragm and strong abdominal muscles, is able to overcome the effect of grav- ity and still maintain equilibrium between the venous and arterial circulation so long as the respiratory act remains undisturbed. When this is disturbed, however, he is still able to maintain the circulation but with certain difficulties in the way. Particular Alterations in Position and Function of the Di- aphragm in Pulmonary Tuberculosis. — It is probably within facts to state that the diaphragm is always disturbed in its function in pulmonary tuberculosis. This disturbance is both reflex and compensatory in character, as previously mentioned. It is rarely symmetrical, but usually more marked on one side than the other. It may be a deficiency in motion; it may be a high posi- tion on one side and a low position on the other ; a high position on both sides ; or a low position on both sides. "When the changes are compensatory in character the position of the diaphragm de- pends on the relative pressures of the thoracic and abdominal cavities and on the contractions and hypertrophies which take place. In many instances where marked displacements of the di- aphragm take place on account of destructive change in pul- monary tissue, there is also a serious wasting in the tissues in the abdominal cavity together with a weakening of the abdom- inal muscles. This wasting tends to lower the intra-abdominal pressure and also permits the abdominal organs to assume a lower position in the abdomen (enteroptosis). At the same time it takes away from the diaphragm one of the chief forces in main- taining its normal position. Likewise the diaphragm loses its power of expressing the blood from the abdominal organs. Its ac- tion is sometimes disturbed by adhesions in the costal angle. Resulting from such conditions we often see, instead of the nor- mal outward motion of the lower ribs anteriorly and laterally, a drawing in with every inspiration. This is often only on one side, sometimes on both. The effect is greatly to embarrass the cir- culation. The aid normally due the circulation from widening the lower portion of the thoracic cavity, is taken away and a nar- rowing is substituted for it. At times the diaphragm is so low 306 COMPENSATORY CHANGES IN TUBERCULOSIS that the heart hangs suspended from the large vessels at the base, as mentioned above. A high position of the diaphragm as we usually meet it, is connected with an increase of fat deposited in the mesentery, gas in the gastrointestinal tract, or some tumor mass in the ab- dominal cavity. The symptoms produced by it are not as serious for the cir- culation as those produced by a downward displacement. In tu- berculosis, however, we have other conditions present, such as the lowered intra-abdominal pressure, the weakened abdominal muscles and the pathological changes in the thoracic cavity, so the situation is different ; and it must also be looked upon as being a condition extremely detrimental to a full and free respiration and as having an embarrassing influence on the circulation. Splanchnic congestion favors acidosis by causing stagnation of the blood column. Lessened abdominal pressure, caused by laxness of the tis- sues, reduced inspiratory act and weakened abdominal muscles, is followed by cerebral anemia, producing headache, dizziness, muscular weakness, and general symptoms of nervousness. It is of great interest to see how far nature will go in her efforts at compensation. In Fig. 40, page 286, I show a wonderful compensation in which nature practically formed a new lobe to the lung and pushed it far over into the right thoracic cavity to fill the space rendered vacant by a destructive process. In the same case I mentioned how a new lobe was made to the liver which pushed far up into the thoracic cavity to occupy the space which could not be filled by the thoracic viscera. In this con- nection I would cite the ideas of Professor Tandler of Vienna, who speaks of the liver as a compensatory organ being able to enlarge to occupy space rendered vacant by loss of tissue. From the foregoing description of compensatory changes which take place in pulmonary tuberculosis it is evident that the symptoms produced by them are varied in nature, and that they may be on the part of the respiratory system itself, or the circu- latory, nervous or digestive system. Effect of Arterial Hypotension and General Wasting of Tis- sues Upon Body Activities. — Hypotension to my mind is an im- EFFECT OF HYPOTENSION 307 portant factor in the general depressed state of these patients. This has usually been thought due to the toxemia, but I be- lieve disturbances in the diaphragm an equally important factor. 10 The disturbance on the part of the diaphragm comes early and lasts as long as activity is present if the case be an early one; and becomes permanent in all cases where destructive changes in the lung or pleural adhesions at the base result. In the case of the advanced disease, the factors, such as general wasting, de- generation of the heart in particular, and displacements of this organ, are added to the toxemia and circulatory changes caused by the disturbance of the diaphragm and coincident respiratory embarrassment. The pulse in quiescent advanced tuberculosis where the heart is fully competent is not far from normal as long as the patient is at rest or even under light exercise, unless large amounts of the pulmonary tissue have been destroyed. If more strenuous work is engaged in, however, the heart is apt to fail to measure up, because it is already working under strain and on its reserve power. The pulse increases to a greater rate than would be nor- mal for the work done and fails to return to the normal within the proper time limit. Where larger amounts of lung tissue have been destroyed the patient may still be comfortable at rest; and yet not be able to do any exercise without manifesting respiratory embarrassment, the pulse being rapid, dyspnea appearing, the patient feeling weak, dizzy or faint. The reason for this is clear. The patient is ordinarily using up all of bis reserve heart power and still is having difficulty in maintaining an efficient circulation. As long as he is at rest the functions of the body are carried on economically as a minimum of energy is demanded. But, when exercise is attempted and more blood is demanded the patient's heart cannot measure up to the emergency, neither can the blood be forced from the splanchnic reservoir where it is stored ; conse- quently the symptoms follow. The flow of blood is four or five times as rapid in active muscles as in resting muscles. Rising to a position ready for walking doubles the requirements of oxygen 10 Enteroptosis and Altered Function of the Diaphragm, Resulting from Intrathoracic Inflammations, New York Medical Journal, December 16, 1911; and Blood Pressure in Pulmonary Tuberculosis, New York Medical Journal, August 31, 1912. 308 COMPENSATORY CHANGES IN TUBERCULOSIS compared with a resting position ; and starting to walk quadruples it. The heart in its weakened condition and its unnatual posi- tion, with the changes in the arterial walls, and the blood stored up in the veins, cannot meet the circulatory requirements. While many of these factors cannot be removed, yet there is something that can be done. The heart cannot be wholly relieved, the arteries cannot be changed, the respiratory movements can- not be restored, but the intra-abdominal pressure can be in- creased to a certain extent by properly applied adhesive straps or suitable abdominal binders so that the venous stasis will be some- what relieved and the onflow of blood to the heart hastened. In this manner, circulatory embarrassment in advanced tubercu- losis can be greatly relieved. An increase of fat in the mesentery in such cases is very desirable and the greatest relief is experi- enced by increasing the patient's nutrition to the point of put- ting on weight. The following case illustrates a very marked degree of com- pensation and the symptoms which arise as a result of it: Case 2414. Housewife, age 32. Entered the sanatorium February 27, 1914. Personal History. — During childhood suffered from diphtheria, scarlet fever, typhoid fever, smallpox, and measles. Tuberculous History. — Five or six years prior to the time of entering the sanatorium the patient suffered from left-sided pleurisy. Two and a half years later she had a diagnosis of tuberculosis made, by the finding of bacilli in the sputum. She was sent to Denver in July, 1912, where she remained, until the time that she entered the sanatorium, with the excep- tion of one month which she spent in Phoenix. Two years prior to the time of entering the sanatorium she was having what were considered as "colds." These were protracted and she had some hoarseness and cough. These were accompanied by sputum which showed bacilli. She also suffered at that time from night-sweats, malaise, lack of endurance, and impaired digestion. Her temperature had been irregular. At times it had been as high as 101°. Her symptoms may be grouped, according to their etiology, as follows: Those Due to Toxemia. Malaise Lack of endurance Digestive disturbances Increased pulse rate Night sweats Fever Those Due to Reflex Cause. Hoarseness Cough Pain in shoulder Those Due to Tubercu- lous Process per se. Frequent and protracted colds Pleurisy Sputum — bacillus-bearing CASE ILLUSTRATING MARKED COMPENSATION 309 Physical Examination. — Physical examination made at the time of en- tering the sanatorium showed a widespread disease affecting the entire left lung and the upper portion of the right. Infiltration was very dense in the upper portion of the left side and there were many rales, indicative of necrosis, throughout the entire lung. There was also evidence of cavity. There was blowing expiration, whispering voice, together with medium rales, metallic in character, near the apex posteriorly. On the right side many rales were also present, indicating that the disease in this lung had also gone on to ulceration. The left lung had contracted markedly, and the mediastinum had shifted toward the left side. The left border of the heart was in the nipple line and the right border was near the middle of the sternum. The right lower lobe was emphysematous. Course of Disease During Treatment. — The course of the disease in this patient has been one of continuous destruction on the left side and steady improvement on the right. This patient has been under observation for thirty months, and at the present time the function of the entire left lung is destroyed. The upper lobe is replaced by cavity. There is also ex- tensive excavation in the lower lobe, and the portion which remains is fibrous in character. The disease in the right lung has healed and the entire lung is emphysematous. Almost continually during the thirty months of observation this patient has had some rise in temperature. At no time has she been free for more than a few days. She also had fever for many months before coming under my care. I wish to illustrate by this case one of the most remarkable compensa- tions that I have ever observed in tuberculosis; and, at the same time, detail the symptomatology which results from the pulmonary destruction, the shifting of the mediastinum, and the shifting of the diaphragm. I shall attempt to describe this by first giving the physical examination of the patient at the present time; second, by a description of the symptoms, as they have been found throughout the course of the disease. Present Condition of Physical Examination. — Inspection. — On inspection we find the patient in a high state of nutrition. Contrary to what would be expected, there is only a slight degeneration of the soft tissues recog- nizable. The muscles and subcutaneous tissue on the left, both anteriorly and posteriorly, appear to be somewhat wasted as compared with those on the right. The left side of the chest, as a whole, is also somewhat smaller than the right. The motion at the base is limited on the left and exaggerated on the right. A pulsation can be seen in the upper por- tion of the left lung, extending from the first interspace down into the axilla. Palpation. — Palpation confirms a slight wasting of the muscles and sub- cutaneous tissue on the left side, as compared with the right. It also con- firms the fact that the left side of the chest is somewhat smaller than the right. It shows the diminution of respiratory motion on the left and increased motion on the right. Aside from this the trapezius and leA^ator anguli scapulae show slight spasm. Palpation of Total Density. — On deep palpation we find that the upper and outer portion of the left lung is separated from the chest wall by the heart, which is pushed firmly against the upper and inner axillary aspect of the bony thorax, there being almost no space between the 310 COMPENSATORY CHANGES IN TUBERCULOSIS mediastinal contents and the upper, inner aspect of the thoracic cage. The apex, or that part of the heart which produces the impulse against the chest wall, presents high in the axilla, in the fifth interspace. The right border of the heart lies fully one inch to the left of the sternum. The lower portion of the left lung is fibrous and there is no air containing tissue below the heart. The diaphragm is drawn up. Posteriorly, from the apex to the lower angle of the scapula, there is an absence of resist- ance, indicative of cavity. This takes in most of the portion of the lung above the lower angle of the scapula. Near the lower angle of the scapula there is a marked resistance, suggestive of dense fibrous tissue; but no air containing tissue can be found below this point. On palpating over the right lung, increased tension, but decreased re- sistance is found throughout. This is also found to extend beyond the center of the thorax to a line perpendicular with the left nipple showing that the right lung pushes over to the middle of the left thoracic cavity. Palpation also shows that the lower border of the right lung has pushed downward and fills in the entire complementary space. Posteriorly, the right lung is prevented from extending beyond the median line by the posterior mediastinum; but its inferior margin extends to the 12th rib. Percussion and Auscultation confirm these findings. The condition, as observed, is schematically represented in the accom- panying Fig. 48, A and B. Symptoms. — Aside from the usual symptoms which accompany chronic active tuberculosis, this patient has suffered from those which belong to the cardioneurotic group; thus, tiring, lack of endurance, exhaustion on the least effort, dizziness on assuming the erect position, dyspnea on ex- ertion, insomnia, and variable appetite. These symptoms are indicative of an inability of the patient to furnish an adequate amount of blood for the body activities. The blood pressure in this patient is very low, be- ing in the nineties, and has been found below ninety. She has a very pronounced splanchnic congestion; her heart, while not markedly rapid when at rest, is quite rapid on exertion. As long as this patient retains the prone position her functions are carried on fairly well; but, as soon as there is an extra demand made upon her, as by exertion, she is unable to supply the extra blood that is required; consequently, she suffers from the symptoms mentioned above. When she assumes the erect position she has a cerebral anemia, which causes dizziness and a feeling of faintness. It will be seen, from the examination findings above, that this pa- tient's diaphragm is working at a disadvantage. On the left side it has assumed a very high position, and on the right side a very low position, consequently the force of the inspiratory act is very much diminished. Eesulting from this diminution of the inspiratory act, the venous reser- voirs throughout the body are in a state of engorgement, while the ar- terial system is deficient in blood. Another factor which operates to increase the relative splanchnic con- gestion is the lowered intra-abdominal pressure, due to enlargement of the cavity by the high position of the diaphragm on the left side. While this is compensated to a great extent, by the low position on the right, it is not fully compensated; consequently, there is a deficiency in sub- stances within the abdominal area, which results in lessened pressure, and, Fig. 48. — Showing schematically the compensation which has taken place between the two sides of the chest, and between the thoracic and abdominal cavities. A, anterior view; B, posterior view. CASE ILLUSTRATING MARKED COMPENSATION 311 consequently, lessened tone of the vessels. Normal exercise calls for an extra amount of blood, and this is supplied from the venous reservoirs, particularly those in the splanchnic area. Now, owing to the deficient inspiratory power possessed by this patient, she is unable to aspirate the blood from the veins into the right heart and furnish the required blood, consequently she suffers from a lack of endurance, an inability to per- form physical work and dyspnea. Treatment. — The respiratory equilibrium of this patient cannot be re- stored. The functional capacity of the diaphragm will always be limited. The splanchnic congestion is more or less permanent; yet, there are certain things which can be done which will partially restore the circulatory equilib- rium in this patient, and give her a fair degree of endurance. This must come about through strengthening of the muscles of the body, depositing a certain amount of fat in the abdominal cavity, and increasing intra- abdominal tension. Exercise would aid this patient by strengthening the body muscles and affording firmer support for the vessels. This is difficult of attainment in this case because there is often a slight rise of temperature present, so that, as soon as we make a certain amount of headway through exercise, she is compelled to assume the prone position again. Such patients must be kept in good nutrition for the intra-abdominal fat is desirable; yet this must not be carried too" far for it will increase dyspnea and flabbiness. Another feature of value in cases such as this is an abdominal support, which will increase intra-abdominal pressure. These cases are not easy to handle, and yet a great deal can be done for them. If the activity of the disease in this case ceases, I think it is probable that a fair degree of en- durance may be attained. As soon as better tone can be obtained in the body, and particularly the abdominal muscles, this, if accompanied by in- creased intra-abdominal fat, and reenforced by an abdominal support, will aid in pressing the blood from the splanchnic vessels. CHAPTER Xn. TRAUMATIC TUBERCULOSIS. The relationship of trauma to tuberculosis deserves attention. The medico-legal aspect of this question at times assumes im- portance. Many cases of tuberculosis have been reported in litera- ture in which trauma is supposed to have been the primary cause of the disease. In former times, when we did not understand the nature of tuberculosis as well as Ave do today, it was more difficult to determine the definite relationship between a previous- ly received trauma and an active tuberculosis. Today, however, knowing the nature of tuberculosis as we do, knowing that bacil- li circulate in the blood more or less frequently after infection has once occurred; and realizing further that implantation of bacilli may be favored by a traumatic condition; and, further, realizing that an old quiescent focus might be disturbed in such a way as to mobilize bacilli through trauma, we can see that sev- eral different conditions might arise whereby there would be a direct relationship between the trauma and tuberculosis. We cannot conceive of trauma itself, unless it be a puncture by a bacillus-infected instrument, producing tuberculosis. Infection must either be present prior to the time of the trauma, or con- ditions must be produced as a result of the trauma which favor some future implantation. To further understand the relationship of trauma to active tuberculosis, it is necessary to bear in mind that a very large percentage of adults have quiescent foci of tuberculosis within the thoracic cavity. They may be in the glands or they may be in the lung tissue itself. The postmortem reports of Hart, re- ferred to elsewhere in these pages, shoAV that more than fifty per cent of adults have tuberculous infections in the pulmonary tissue; but by far the greatest proportion of these will remain quiescent during the life of the patient. However, if disturbed by trauma, a quiescent focus may be caused to take upon itself ac- tivity, and produce clinical tuberculosis. The effect of trauma RELATIONSHIP OF TRAUMA TO TUBERCULOSIS 313 in mobilizing bacilli may be readily appreciated by recalling how such organs as the liver and spleen are often raptured as a result of a blow over them. As physicians, it is our duty to understand this question in order that we may be able to render a fair judgment in cases which come to us for an opinion. From what has previously been said it can readily be under- stood that a variety of conditions might arise whereby it would be necessary to determine the relationship between trauma and existing active tuberculosis. The problem is rendered more dif- ficult because many patients suffer from active tuberculosis for a prolonged period without having a diagnosis made. Trauma might be either the actual cause of liberating bacilli from a previously latent focus or of causing a spread and in- crease in severity of active disease which is already present; or, it may injure the tissues and favor infection in a part of the lung tissue which had not previously been infected. In each of these instances the trauma will stand in a causative relationship. In the first, it must be looked upon as the precipitating cause of clinical tuberculosis. In the other instances it would be looked upon as having an influence in increasing the severity of already existing clinical tuberculosis, and not as standing in the relation- ship of producing clinical disease. Therefore, before determin- ing the relationship of trauma to an existing active tubercu- losis, it is necessary to know the antecedent history of the pa- tient. One should know whether an active tuberculosis had pre- viously existed. In forming an opinion as to whether or not a previous clinical tuberculosis had existed, we would be obliged to base it upon the presence or absence of clinical history of some previous attack of tuberculosis, or a clinical history of suspicious symptoms immediately prior to the time of injury. A patient who had previously suffered from a more or less active tuberculosis, but who had attained a healing of the same, should be looked upon in the same light as a patient who was pre- viously suffering from a quiescent unrecognized lesion. Such an individual would be more apt to be seriously injured by trauma than an individual who was suffering from a small lesion. If the patient who had previously suffered from clinical tubercu- 314 TRAUMATIC TUBERCULOSIS losis, was well and had been free from symptoms for months prior to the injury, we would then be compelled to look upon the trauma as standing in direct causative relationship to an active lesion following injury. In this connection, however, we must bear in mind that lesions that are extensive, even though healing has been attained, now and then show evidence of be- coming active again in after years ; but, if activity had not mani- fested itself in any clinical symptoms or physical signs prior to the trauma, we would consider the trauma as being the active factor in the production of the clinical disease. For cases of active clinical tuberculosis to be definitely as- signed to trauma as the agency in their active causation, the symptoms must appear promptly following the injury. The spreading must take place within the time that implantation and the development of tuberculosis would usually occur, — that is within a period of a few weeks. In this connection we must realize that it is possible for bacilli to be mobilized in small numbers and produce very small metastatic foci. Clinical tu- berculosis might result from such an infection, yet require a con- siderable time for the bacilli to be implanted and form new metastases; and, in such cases, it might be difficult to give an accurate opinion. In cases, however, where the symptoms show themselves within a few weeks after the injury, the relationship can hardly be doubted. That a previous focus may, as a result of trauma, assume activity, which results in the escape and scat- tering of bacilli to new tissues, is entirely reasonable. On this point so able an authority as J. Orth 1 makes the important state- ment that crushing or concussion of the thorax might produce such a marked injury to the tissues, even those which were not lying immediately under the point of trauma, that mobilization of bacilli in a quiescent focus might take place. The truth of this fact is impressed upon us in the experiments which are being reported from soldiers in the present war. It is not uncommon to find tuberculosis follow immediately a gun- shot wound of the thorax. This can be explained on the ground that a projectile, in passing through the pulmonary tissue, pro- trauma und Lungentuberkulose Vier Obergutachten erstattet von Geheimrat, Zeitschrift fur Tuberkulose und Heilstatenwesen, Bd. xxv, Heft. 1, 1915. RELATIONSHIP OF TRAUMA TO TUBERCULOSIS 315 duces a trauma in tissues which have previously been infected, and thus causes an escape of the enclosed bacilli with resultant formation of new foci. This can occur either in quiescent lesions or lesions that are active. There is quite a large percentage of gunshot wounds of the thorax which are followed by active clini- cal tuberculosis. I have seen several cases of supposed traumatic tuberculosis, but, in most instances the injury had been received so long prior to the time of the active disease that no connection could be estab- lished. In most instances, the disease was at the apex while the trauma had been elsewhere. The diagnosis of traumatic tubercu- losis had been made simply because the patient had previously re- ceived an injury to the chest. The following case illustrates how injury to the chest, pro- ducing contusion of tissues may increase the symptoms and pro- duce a more rapid course in a patient who was previously suf- fering from active tuberculosis. Further, it will be noted, that it is quite probable that the injury to the tissues in this instance produced a condition which favored implantation in a new area. The patient was a man of about thirty years of age. He re- ceived an injury by stumbling and falling on a piece of iron, which caused a fracture of the sixth rib on the left side in the anterior axillary line. The rib punctured the lung, and was fol- lowed by spitting of blood. Traumatic pleurisy followed at once. I examined the patient within two months after the occurrence of the hemorrhage, and found a localized tuberculous process surrounding the point of injury. The inflammatory process was the seat of marked activity, causing toxemia with rise of tem- perature. This patient had previously been suffering from a tuberculous process of the left apex, moderate in extent, and slightly active. The weak point in the argument in this case is that I had not examined the patient prior to the time of his injury, and can- not personally vouch for the fact that there was not an old lesion at the point of injury. However, he had been examined shortly before receiving the injury by a competent man, who found no evidence of trouble at the base. The fact that there was an area entirely free from involvement between the lesion at the apex and 316 TRAUMATIC TUBERCULOSIS the more extensive one at the base, together with the fact that the active disease at the site of the trauma, apparently came on promptly after the injury, led me to believe that this was prob- ably a new localization in which implantation of bacilli had been favored by the contusion of the tissues. I am not unmindful of the fact, however, that there might have been a small quiescent focus in the tissues at the point of injury, from which bacilli escaped as a result of the contusion. In this case, we cannot look upon trauma as being a direct cause of the clinical tuberculosis, but we are forced to the con- clusion that it was, in all probabilities, the cause of the new focus at the base of the lung, and its relationship to the disease in ques- tion was one of increasing its activity and hastening its progress. The next case answers all the requirements necessary for a diagnosis of traumatic tuberculosis. Evidence is present that there was an old lesion affecting the hilus and the apex of the left lung. From this, bacilli were mobilized by the trauma re- ceived at the time of the accident. Prior to the time of the in- jury, the patient was in perfect health, and gave no history of ever having shown symptoms indicative of active tuberculosis. Immediately following the injury, the symptoms of active tuber- culosis appeared and the diagnosis was confirmed by the pres- ence of physical signs in the chest, the x-ray, and the finding of bacilli in the sputum. . Case 2966. Clinical History. — Female. Always strong and robust. Lobar pneumonia running typical course when fifteen years of age. Mumps during college life. Operation on turbinates for occlusion of the nares two years ago. Otherwise no illness until, following an automobile accident which occurred on Oct. 20, 1915, the patient was rendered unconscious and received severe injuries to the lower right chest and over the left shoulder. A slight hack- ing cough followed immediately, apparently due to the trauma to the pleura. This persisted. Shortly thereafter, about November 13, an x-ray plate showed fluid in the right pleural cavity. The patient's cough continued and increased. The sputum which first appeared December 1, examined December 6, 1915, showed tubercle bacilli. Repeated physical examina- tions showed distinct tuberculous involvement. Physical Examination. — Examination made about six months after the accident showed the following: The patient is well nourished. Inspection reveals somewhat diminished motion at both bases, more marked CASE ILLUSTRATING TRAUMATIC TUBERCULOSIS 317 anteriorly on the right side, owing to pleural inflammation; but posteriorly- more marked on the left. Condition of the muscles and subcutaneous tissue. — There is a slight degen- eration of the subcutaneous tissue near the hilus on the right side; also slight degeneration of the sternocleidomastoideus, and upper portion of the pee- toralis. The right sternocleidomastoideus also shows marked tone. There is some question whether it could be in reflex spasm, or be a part of the gen- erally well developed muscular condition resulting from continuous use. The left sternocleidomastoideus, scaleni, and upper fibers of the pectoralis show marked spasm. Posteriorly, the left trapezius, and levator anguli scapulae are slightly degenerated, indicative of an old lesion. The same muscles, with the rhomboidei, are in marked spasm, indicative of new activity. Ap- parently no spasm on the right side posteriorly. Deep palpation reveals an increased density to the 4th rib anteriorly on the left and in the region of the hilus on the right. Posteriorly, there is an increased density to the middle of the scapula on the left and in the inter- scapular region on the right. Percussion on the left shows slight dullness to the 4th rib anteriorly near the sternum and to the 3rd rib toward the axillary line. There is slight impairment near the sternum on the right; posteriorly, impairment with slight dullness to the middle of the scapula on the left, and in the inter- scapular region on the right. Auscultation reveals a roughened note accompanied by numerous medi- um and fine rales from the apex to the 4th interspace on the left, more marked near the sternum than near the axillary line. No rales on the right side, but slightly altered breathing near the sternum. Posteriorly, there is roughened breathing, with medium and fine rales extending to the mid- dle of the scapula on the left side, with altered breathing near the vertebras on the right in the interscapular space. There are a few fine rales which seem to be of pleural origin in the lower right anteriorly. Diagnosis. — Pleurisy of traumatic origin at right base. Pulmonary tu- berculosis. Thickening about the hilus of the lung on the right, with slight extension toward the apex. Old foci in the upper portion of the left lung, upon which an active process has been engrafted, most probably as a re- sult of trauma. Active tuberculosis in the upper half of the lung. Comment. — The physical condition of the patient prior to the accident; the absence of clinical symptoms; and the fact that she was able to carry on the difficult and strenuous work incidental to her professional life, without even being tired, or showing any other symptoms that might be attributed to an active tuberculous lesion, indicates that any infection that was present prior to this accident was quiescent. The indications, however, are that there was an old hilus infection present, and also a quies- cent focus in the apex of the left lung. This is indicated not only by the character of the breathing on auscultation, but by the degeneration of the muscles and soft tissues covering this apex. This condition, how- ever, is not inconsistent with good health, as is shown by such patho- logical reports as those of Hart, which show that in all autopsies made on adults dying of ordinary causes, an apical tuberculosis is present in more than fifty per cent. The great majority of these infections are quiescent and produce no recognizable symptoms during the life of the 318 TRAUMATIC TUBERCULOSIS patient. As long as the patient remains in good physical condition, he seems to be free from the danger of the infection taking upon itself activity. The clinical course of the infection, following the accident, is extremely interesting. Immediately following, there was a traumatic pleurisy at the right base. There was also a dry cough which, at first, was thought to be referable to the pleurisy; but the pleurisy soon disappeared, while the cough continued to increase in severity. The examination of the chest about the middle of November revealed no physical signs of active tuber- culosis. Such could not be expected at this early date because an infec- tion resulting from an activity lighted up by such an accident would most likely require a longer period to produce recognizable symptoms and signs. By the first of December the cough had still increased in severity and expectoration appeared which, on the 6th day of December, was shown to contain tubercle bacilli. Physical examination at this time also revealed an active tuberculous lesion in the upper left lung. The whole clinical course in this case seemed to point definitely to the accident as being the cause of the activity. CHAPTER XIII. IMPORTANT ANATOMICAL AND PHYSIOLOGICAL FACTS TO BE CONSIDERED IN MAKING PHYSICAL EX- AMINATION OF THE ORGANS WITHIN THE THORAX. In the course of time the literature of any subject becomes a mixture of truth and error in spite of the closest scrutiny. To this rule, the diagnosis of diseases affecting the organs within the thoracic cavity is no exception. Aside from the logical analysis of signs and symptoms, if we would make more accurate diagnoses it is necessary not only to improve our technic of making examinations, but also to gain a more accurate conception of the parts and organs to be examined. This statement holds for anatomical and physiological as well as pathological considerations. A familiarity with the following points will show some of the common sources of error in physical examination. Projection of Lung on Anterior Surface of Chest. — From, the midsternum to the acromial end of the clavicle above and to the external border of the axillary fold lower down, is a distance of some six inches in ordinary chests. One must not think, how- ever, that the underlying lung extends from the midsternum to the acromion or the axillary fold. The external border of the lung is bounded by the inner surface of the ribs. The inner surface of the first rib does not extend beyond the inner fourth of the clavicle ; the inner surface of the second, not beyond the inner third of the clavicle; and the inner surface of the third, not beyond the inner half of the clavicle, consequently, the an- terior surface of the lung is small in comparison with the entire anterior surface of the chest wall as may be seen in Figs. 49 and 50. The latter being a frontal section gives a splendid idea of the relative amount of lung which presents. One should bear this in mind in making examinations. The ear or stethoscope 320 PHYSICAL EXAMINATION OF ORGANS OF THORAX is near lung tissue only over the inner third of the interspace im- mediately below the clavicle and the inner half of that next lower. Above the clavicle, the apex is found between the two heads of the sternocleidomastoideus, and does not extend out in the supraclavicular notch as is usually taken for granted. Normal Border of Lung's. — The normal borders of the lungs are shown in Figs. 51, 52, and 53. The apex of the lung extends 3 to 5 cm. above the clavicle. The lower borders are at about the same height on the two sides. For the man in middle life Fig. 49. — Showing the relationship of the anterior surface of the lung as confined by the bony thorax to the soft structures forming the anterior surface of the chest. they are on a level with the sixth rib in the mammary line, the eighth in the axillary line, the tenth in the scapular line, and at the junction of the eleventh rib with the vertebra at the vertebral border. (See pages 322, 323, and 324.) The apex is the nearest the surface between the two heads of the sternocleidomastoideus, as before mentioned. On ordi- nary quiet respiration the movement of the lower border of the lung is scarcely to be determined by percussion and palpation, being only 1 to 2 cm. ; but the difference between forced inspira- Lobus sup. pulm. dextr xjl: Lobus sup. pulmon. sin. Art. pulmon. uricula sin. cordis Valv. bicuspi- dalis u. Ventr. cordis sin. Lobus inf. pulmon. sin. Diaphragma Fig. 50. — Frontal section through thorax of 26-year old man. Section made midway between mammary and axillary line. (Viewed from the front.) The thickness of the soft tissues covering the lung may be seen and their influence on palpation, percussion, and auscultation may be inferred from this figure. It also shows the relationship of the lungs themselves to the anterior surface of the chest wall. (Corning.) DIAPHRAGM AT DIFFERENT AGE PERIODS 321 tion and forced expiration can be readily determined for it amounts from 6 to 10 cm. Position of Diaphragm at Different Age Periods. — The posi- tion of the diaphragm varies with the age of the patient. Figs. 54, 55, and 56, page 324 (Mehnert), show the diaphragm at birth, at 36 years of age, and at 72 years of age. In develop- ment, the diaphragm comes from high up in the cervical region and consequently receives a portion of its innervation from the cervical portion of the cord; the central portion being supplied by the phrenics which take their origin from the third and fourth or fourth and fifth cervical segments. This fact is important in explaining the pain which is found in the shoulder areas sup- plied by nerves from the third and fourth cervical segments, in cases of diaphragmatic pleurisy, when the central portion of the organ is involved. The costal portion of the diaphragm, on the other hand, is supplied by the lower six intercostal nerves, which also supply the muscles and skin of the upper abdominal wall. This fact accounts for the rigidity and pain over these parts in diaphragmatic pleurisy when the costal portion is inflamed. Position of Sulci Which Separate Lobes. — The importance of understanding the position of the sulci which divide the lung into lobes is not so great in early cases as it is in more extensive ones. Tuberculosis extends in the lung most readily by forming metas- tases in lymph spaces adjacent to the original focus; or by metas- tatic infection through the bronchi. Extension through lym- phatic metastases is confined, for the most part, to the areas adjacent to the previous focus, and does not readily leap from one lobe to the other. Bronchogenic infection, for the most part, follows the same course, but it may, like hematogenic in- fection also go from one lobe to the other, or from one lung to the other. The divisions between the lobes is shown in Figs. 51, 52, and 53. Clinically, the division between the upper and lower lobe may be roughly marked by placing the hand upon the opposite shoulder, which throws the lower point of the scapula out toward the axilla, and drawing a line along its inner border. This line when prolonged, as in Fig. 57, page 324, roughly marks the division be- tween the lobes. 322 PHYSICAL EXAMINATION OF ORGANS OP THORAX In advanced tuberculosis the greatest destruction of pulmo- nary tissue usually occurs in the upper lobes, and is followed by contraction. A compensatory emphysema follows in the lower lobe and in the other lung, causing their enlargement. In consequence of these changes there is a shifting of the inter- lobular septum, mediastinum, and diaphragm. It is not infre- L0W£R MARGIN OF LUNG-- LOWER MARGIN OF PLEURA -- OWER MARGIN OF LUNG -LOWER MARGIN OF PlEDRA Fig. 51. — Illustrating the normal borders of the lungs and the location of the interlobular septi. Anterior view. (Corning.) quent in advanced cases with marked destructive processes in one upper lobe, to find it contracted to a small fibrous mass and the lower lobe anteriorly pushing up toward the apex. Such a case is shown in Fig. 40, page 286, where the middle lobe is shown as a fibrous string and the lower lobe pushed upward to the third rib. In this ease the compensation was so great that PERITRACHEAL AND PERIBRONCHIAL GLANDS 323 most of the right side of the chest on the anterior surface as well as the left was occupied by the left lung. The Projection of the Peritracheal and Peribronchial Glands on Body Surface. — The projection of the peritracheal and peri- bronchial glands on the surface becomes of great importance LOWER MARGIN OF LUHG LOWER MARGIN OF PLEURA -- Fig. 52. — Illustrating normal borders of the lungs and interlobular septi. Posterior view. (Corning.) now that hilus infection has assumed such great proportions. Fig. 15, page 94, shows the location of the tracheal and bronchial lymph glands which are so commonly infected and enlarged. Figs. 58 and 59 show that dullness due to enlargement of such glands in adults would be usually expected in the interscapular spaces from the third to sixth thoracic vertebrse. Dullness from 324 PHYSICAL EXAMINATION OF ORGANS OF THORAX these glands is most common in children, however, and is found higher than in adults. Mehnert 1 shows the changed position of the bifurcation of the trachea according to age. At birth it is at the third or between the third and fourth, or at the fourth tho- racic vertebra; at two years of age it is between the fourth and fifth; at thirty-five between the fifth and sixth; at sixty in the middle of the sixth; and at seventy- two on a level with the upper third of the seventh. The mediastinal glands are nearer the pos- terior surface than the anterior, consequently are more readily detected posteriorly. Anteriorly, the bifurcation of the trachea Fig. 53. — Illustrating the normal borders of the lungs and the location of the interlobular septi. Lateral view. A, right; B, left. (Corning.) is usually given as taking place on a level with the junction of the second costal cartilage with the sternum, but from data quoted above its position must be variable. (See pages 326 and 327.) Muscles Employed in Normal Respiration. — Inasmuch as defi- cient motion of the chest wall is a very important and almost con- stant accompaniment of inflammation in the lungs and pleura; and, inasmuch as some disturbance on the part of the motion of the chest wall is usually found in both active and healed lesions *Uber topographische Altersveranderungen des Atmungsapparates, Gustav Fischer, Jena, 1901. r -< * » 9 \ / Fig. 54. — Position of the diaphragm and intrathoracic and abdominal organs at birth. Compare with Figs. 55 and 56. (Mehnert.) I * . ; <*■ Fig. 55. — Position of the diaphragm and intrathoracic and abdominal organs in adult 36 years of age. Compare with Figs. 54 and 56. (Mehnert.) Fig. 56.- -Position of the diaphragm and the intrathoracic and abdominal organs in adult 72 years of age. Compare with Figs. 54 and 55. (Mehnert.) Fig. 57. — Showing the location of the sulcus between upper and lower lobes as deter- mined by placing the hand on the opposite shoulder and prolonging a line drawn along the inner border of the scapula. MECHANICS OP RESPIRATION 325 of the lung and pleura, it becomes important for the examiner to acquaint himself carefully with the mechanics of respiration and familiarize himself with the normal movements. The inspiratory act prepares the passages (nose and larynx) for the entrance of air and enlarges the thorax anteroposteriorly, laterally and superoinferiorly. Normal inspiration is produced by the contraction of the following muscles : 1. Muscles of nose (not in quiet respiration as a rule in man) innervated by nervus facialis (seventh). 2. Muscles of the larynx — innervated by nervi laryngei su- perior et inferior (tenth). 3. The diaphragm innervated by nervi phrenici from the third and fourth or fourth and fifth cervical segments ; and the seventh to twelfth intercostals. 4. Intercostales externi et intercartilageni innervated by all thoracic segments of the cord. 5. Levatores costarum longi et breves innervated by filaments from the spinal nerves. The sinking of the diaphragm is the more important factor in the male while the elevation of the ribs is more important in the female. On forced inspiration, however, all muscles are brought into play and the chest is enlarged in all its dimensions. Influence of Diaphragm in Respiration. — When sleeping or re- clining, if lying on the back, both men and women assume the thoracic type of respiration. When lying on the side, on the other hand, they assume the abdominal type. The diaphragm in its innervation is reflexly associated with the sympathetics which supply the lung, the afferent impulses passing through the rami communicantes from the superior cervical ganglion to the cer- vical segments which give origin to the phrenics. The com- munication between the sympathetics and the cervical nerves is as follows: from the superior ganglion to the first to sixth cervical nerves; from the middle ganglion (or corresponding position of the trunk when this is absent) to the fourth, fifth, sixth, and seventh cervical nerves; and from the inferior ganglion to the seventh and eighth cervical and first thoracic nerves. The efferent impulses pass out through the phrenics to the diaphragm and cause a limited motion on inspiration which becomes a valuable sign in inflammations of the lung. It also 326 PHYSICAL EXAMINATION OP ORGANS OF THORAX becomes important because of its influence in lessening the in- spiratory act. This, as shown elsewhere (page 301), lessens the suction action which delivers the blood to the heart, conse- quently, delivers less blood to that organ which, in turn, ac- commodates itself to a lessened quantity and becomes smaller. From a lessened output the arteries also contain less, showing Fig. 58. — Showing the position of the bifurcation of the trachea and the peritracheal and peribronchial glands projected upon the anterior surface of the chest in a young adult. (Gerhartz.) an arterial anemia, and giving a lower blood pressure, while the veins are full, giving a venous congestion. This latter does not particularly manifest itself in the early part of the disease while methods for compensation are still available; but, later, it shows throughout the body. Congestion of the abdominal ves- sels is especially pronounced, for the suction action of the normal inspiratory act is lessened, and they are also deprived of the full compressing force of the contracting diaphragm upon the ab- dominal viscera. Wenckebach has aptly compared the compres- MECHANICS OP RESPIRATION 327 sing action of the contracting diaphragm upon the liver to that of the compression of a hand on a sponge. Anything which interferes with the inspiratory act produces the effect above described. This may be understood by Fig. 60A and B. When conditions have arisen in the chest which make it necessary to call the accessory muscles of respiration into use, any influence interfering with their action will also affect the force of the inspiratory act. (See page 328.) Muscles Employed in Forced Respiration. — The accessory muscles of respiration also become very important factors in the diagnosis of tuberculosis because of the fact that they take their nerve supply from the segments of the cord which receive af- ferent impulses through the rami communicantes from the sym- Fig. 59. — Showing the position of the bifurcation of the trachea with the peritracheal and peribronchial glands projected upon the posterior surface of the chest in a young adult. (Piersol.) pathetics in the inflamed lung, the same as just mentioned for the diaphragm. This fact will be evident from the following table of accessory muscles of respiration and their innervation : 1. Scalenus anticus, medius and posticus, — innervated by fila- ments from the cervical and brachial plexuses. 2. Serratus posticus superior, innervated by nervus dorsalis scapulas from the fifth cervical nerve. 3. Sternocleidomastoideus innervated by ramus externus 328 PHYSICAL EXAMINATION OF ORGANS OF THORAX nervi aceessorii and filaments from the second and third cervical nerves. 4. Trapezius innervated by ramus externus nervi aceessorii and third and fourth cervical nerves. 5. Rhomboidei innervated by dorsalis scapulae from the fifth cervical nerve. 6. Extensores columnge vertebralis innervated by posterior branches of the spinal nerves. 7. Pectoralis major, innervated by external and internal an- terior thoracic nerves from the fifth, sixth, seventh and eighth cervical and first thoracic nerves. X' A FF' Fig. 60. — Schematic illustration of the influence of the diaphragm in enlarging the intra- thoracic space. A, normal respiration; B, illustrating the effect when the movement of one side of the diaphragm is lessened. The intrathoracic space fails to be enlarged to the extent that motion of the chest and abdominal wall EF, in figure B, is limited. 8. Pectoralis minor, innervated by seventh and eighth cer- vical and first thoracic nerves. Thus it is clear that these muscles, together with the dia- phragm, are innervated by fibers from the cervical segments of the cord which are in communication with and receive afferent impulses from the inflammation in the lung through the cervical sympathetics and the rami communicantes. Acute inflammation in the lung is expressed reflexly in motor; and chronic inflamma- tion in trophic changes in these muscles the same as acute ap- SEGMENTAL DISTRIBUTION OP SOMATIC NERVES 329 pendieitis is expressed in a motor reflex in the abdominal muscles. It is self-evident then, that the condition of these muscles offers useful data upon which to suspect both active and chronic intra- thoracic inflammations and thus becomes of value in the diagnosis of pulmonary diseases. Segmental Distribution of Nerves to the Somatic Muscles. — With our ever increasing interest in visceral neurology, we are not only led to study the functional changes in the internal vis- cera themselves, but also to determine the manner in which dis- eases of the internal viscera are reflected in the superficial tissues of the body. The key to this study lies in the fact that the body is made up of many different segments, and that each portion of the surface of the body which receives innervation from a given segment, is also bound, by reflex paths, to the various internal viscera which receive their nerve supply from the same segment. In order to understand this we must bear in mind the develop- mental relationship between the cells in the spinal segments and the cells of the sympathetic system. Early in the course of evo- lution, the cells of the sympathetic nervous system pushed out from the segments of the cord, and today lie without in their own ganglia. Each spinal nerve receives its innervation from cells which lie within the cord itself. The cells which give origin to the sympathetic fibers going to the internal viscera which should take their innervation from that same segment of the cord, on the other hand, lie in the ganglia without the cord. There is still, however, connector fibers which run between the cells of the segment in the cord and the cells in the sympathetic ganglia which have been pushed off from that segment, thus preserving the segmental relationship. The reciprocal relationship between the viscera supplied from a given segment and the somatic structures supplied by the same segment must ever be borne in mind. Any stimulation, or irrita- tion of the superficial structures of the body supplied by a spinal nerve, produces disturbances in the nerve cells of that segment of the cord from which it takes its origin, and this is transferred through the connector fibers to the cells in the corresponding sympathetic ganglion which give origin to the sympathetic fibers supplying the internal viscera. In case of inflammation, this ir- ritation of the cells in the cord produces pathological change 330 PHYSICAL EXAMINATION OF ORGANS OF THORAX either temporary or permanent, which is reflected from the somatic structures to the internal viscera; and conversely, when internal viscera are inflamed, from the internal viscera into the somatic structures. If only the paths of these afferent nerves can be accurately worked out we can then anticipate the localization of the result- ant reflex action. From this it can be seen that every inflammation of an internal organ produces an irritation in the cells of that segment of the cord which is in communication with it through the sympathetic afferent fibers and the connecting rami communicantes ; and that this may be expressed in the superficial tissues in sensory, motor, and trophic disturbances. "While there are some difficulties in the study of the exact innervation of the somatic structures, there is still greater dif- ficulty in determining the intricate innervation of the internal viscera. At the same time, the whole scheme has been worked out in a manner to be sufficiently accurate for clinical work. There are still many clinical observations to be made and many physiological facts to be determined. The time is now ripe for clinicians and physiologists to cooperate and aid in the working out of these phenomena. For the study of the reflex motor and trophic phenomena which are seen when internal viscera are in- flamed, I append the following table, prepared by Wichmann, and quoted by Bechterew 2 in which the somatic muscles, to- gether with their segmental innervation, are shown. . Eef erence to this table will facilitate the understanding of the various reflexes which are described in the text, such as the reflex from the lungs to the muscles of respiration; that of diaphrag- matic pleurisy; intercostal pleurisy; tuberculosis of the intes- tines ; and tuberculosis of the kidney, each one of which will be described under its proper heading. I. Cervical Roots. C I-H Deep neck muscles. C I-III Hyoid muscles. C II (T-TTT) Sternocleidomastoideus (Nervus accessorius Willisii). 2 Die Funktionen der Nervencentra, vol. i, Gustav Fischer, Jena, 1908. Porus acusticus > externus Processus mastoi- _ deus Processus styloideus -V M. masseter 1 M M. digastricus (venter posterior) M. splenius capitis — M. digastricus (venter Corpus anterior) ossis hyoideus M. thyreohyoideus M. omohyoideus (venter superior) M. sternohyoideus M. omohyoideus Acromion A (venter inferior) Clavicula Fig. 61. — Showing muscles of the neck (side view). Sternocleidomastoideus and scaleni are of special diagnostic importance. (Spalteholtz.) Fig. 62.— Showing the pectoralis. (Spalteholtz.) SEGMENTAL ORIGIN OF SPINAL NERVES 331 C II-IV Trapezius. According to Gowers, the middle and lower portion of this muscle is innervated through the lower cervical, and even the upper thoracic segments. C n-Vm Longus colli. III- VI Scalenus anticus. C ni-VTH Scalenus medius. C IV (III) Diaphragma (Nervus phrenicus), Levator scapulae. C IV-V Ehomboidei. C V (VI) Supra- and infra-spinatus, Teres minor, Subscapularis, Subclavicus. C V-VI Biceps brachii, Brachialis (Nervus musculo-cutaneous). V-VI I L Scalenus posticus. C VE (V) Deltoideus (Nervus axillaris), Teres major, Pectoralis major (pars clavicularis), Coracobrachialis. C VI- VII (V) Serratus anticus major; Supinatores (Nervus radialis). C VI-VEH Latissimus dorsi. C VII (VI) Triceps brachii (According to Oppenheim the triceps cen- ter lies lower in the cord), Eadialis externus, Ab- ductor pollicis longus (Nervus radialis), Eadialis in- ternus, Pronator teres (Nervus medianus), Musculi thenaris (whose center, according to other observers, also lies lower in the cord). C Vn-VHI Extensores digitorum, Ulnaris externus (Nervus radialis), Pectoralis major and minor. C VIII (VII Flexores digitorum, Pronator quadratus, Palmaris longus Th. I) (Nervus medianus). C VTII-Th. I Ulnaris internus (Nervus ulnaris). The small muscles of the hand, with the exception of the thumb, in so far as these are innervated through the median nerve, belong to a higher segment. II. Thoracic Roots. Serratus posticus superior. Intercostals. Eectus abdominis, Obliquus abdominis externus. Transversus abdominis, Obliquus abdominis internus. Serratus posticus inferior. m. Lumbar Boots. Psoas, Cremaster. Iliacus. Sartorius, Quadriceps femoris, Peetineus, Adductores fem- oris, Eectus internus. Obturator externus. Tensor fasciae latee (Nervus glutseus superior), Semimem- branosus (Nervus ischiadicus), Tibialis anticus (Ner- vus peroneus). L IV-S I Glutei medius et minimus (Nervus gluteus superior) Ge- melli, Quadratus femoris (Nervus ischiadicus). T i-rv T II-XI T v-xn T vri-L i T rx-xn L in l n-ni L II-IV L III-IV L IV-V 332 PHYSICAL EXAMINATION OF ORGANS OP THORAX L V Semitendinosus (Nervus ischiadicus), Plantaris (Nervus tibialis), Extensores digitorum (Nervus peroneus). L V-S II Gluteus maximus (Nervus gluteus inferior), Biceps fem- oris (Nervus ischiadicus), Gastrocnemius, Soleus, Tib- ialis posticus, Flexores digitorum (Nervus tibialis). IV. Sacral Roots. S I Obturator internus (Nervus ischiadicus). S II Pyriformis (Small muscles of the sole of the foot with the exception of the abductor pollicis and Extensor digi- torum brevis, which belong to the 5th Lumbar and 1st Sacral. S III-V Muscles of generative organs. Influence of Muscles and Soft Tissues on Physical Findings. — Figs. 61, 62, 63, and 64, pages 330 and 332, show the most important neck and chest muscles. It is necessary for one to familiarize him- self with them in order to appreciate the influence which motor and trophic changes in them exert upon palpation, percussion and aus- cultation. The thickness of the soft tissues covering the lung varies over different portions of the chest wall. Over the pectoral, scapular and interscapular regions it may be one or two centimeters in individuals with slight musculature or four or five centimeters in those in whom these tissues are well developed. The apex of the lung, posteriorly, where covered by the trapezius, lies from four or five centimeters to six or eight centimeters below the sur- face. The influence of this varying thickness of soft tissues upon the data obtained in physical examination is extremely important. It can readily be understood that such musculature when of increased tone (spasm) will afford different data from what it would when normal. This can be appreciated particularly on percussion. It can also be seen that, when a degenerative process affects these soft tissues (skin, subcutaneous tissues and muscles all degenerate), as happens regularly in chronic tuberculosis, re- sulting in a loss of substance at times up to nearly half the total amount, this, too, greatly modifies the data obtained upon phys- ical examination. The importance of the tone of these soft structures may be inferred from their thickness as shown in Figs. 65 A, B, and C, page 334. This degeneration is all the more impor- tant because it is regional in character and usually affects one side Processus spinosus vertebrae cervicular VII Spina scapulae Acromion M. splenius capitis M. sternocleidomastoideus ,M. trapezius Fascia infraspinatus M. deltoideus Processus spinosus vertebrae thoracalis XII M. triceps brachii M. teres major M. rhomboideus major """ M. latis- simus dorsi Fascia Iumbodorsalis (posterior layer) Fig. 63.— Showing superficial muscles of the neck and back (posterior view). Trapezius of great diagnostic importance. A and B, portions of trapezius which show spasm and degeneration best. (Spalteholtz.) Protuberantia occipitalis . Processus spinosus vertebras cervicalis VII y M. semispinalis capitis "M. splenius capitis et cervicis , M. levator scapulae »M. rhomboideus minor /' , M. rhomboideus major i Fascia infraspinatus ; M. supraspinous ; ' M. deltoideus Processus spinosus vertebra; thoracalis VI M. latissimus dorsi i M. triceps M. teres M. teres brachialis major minor Fig. 64. — Showing the second layer of muscles of the back. Levator anguli scapula: and rhomboidei of special diagnostic importance. (Spalteholtz.) OCCUPATIONAL CHANGES IN THORAX 333 (the side of the oldest lesion) far more than the other. The effect on the shoulder girdle is shown schematically in Fig. 90, page 422, and clinically in Figs. 95, A and B, page 466. Common Occupational Changes in the Soft Tissues of the Thorax. — Inasmuch as the condition of the soft structures cover- ing the thorax offers important diagnostic signs in pulmonary tuberculosis, it is necessary that we familiarize ourselves with those things which cause a departure from the normal. The discussion of the pathological variations from the normal will be found elsewhere in these pages. In my study of the reflex spasm and degeneration of the muscles, and the degeneration of other soft tissues, caused by inflammatory processes within the lung, the conditions which have caused me most trouble have been those due to changes which result from occupational influences. Right-handedness is almost universal. The fact, however, that there are a large number of people who are left-handed, gives us an opportunity to draw fairly accurate conclusions from the changes which come from more or less constant use of one hand in preference to the other. We have found that people who use their right hand most, not only in muscular acts, but in carrying objects as well, have a lowering of the shoulder on that side, as compared with the other shoulder. In persons who are left- handed, we find this lowering of the shoulder on the left side. This indicates that there are certain changes which take place in the supports of the shoulder girdle on account of constant use. Examination shows this to be a lengthening; and, ap- parently, at least, a degeneration of the shoulder muscles, which is particularly emphasized in the trapezius and levator anguli scapulas. There is also an apparent degeneration or thinning noted in the peetoralis on the side of the arm used most. This lengthening and degeneration of the muscles is almost universal in the human family, except in those individuals who do heavy work with these muscles. Such individuals very often show a marked hypertrophy which almost, and, at times, wholly, over- comes any stretching or thinning of the muscles that would other- wise be evident. Normal Variation in Physical Types and Their Visceral Func- tion. — An error in both physical and functional diagnosis arises from attempting to consider all individuals from a given stan- 334 PHYSICAL EXAMINATION OF ORGANS OF THORAX dard. Such is impossible. Among other things, individuals dif- fer in general contour of the body, in size, in weight, in the amount of flesh, in the shape of the thorax, in the shape of the abdomen, in muscular strength, and nerve stability. Of neces- sity, the organs must differ in form and functional capacity. We cannot have the same shaped lungs, the same shaped liver, the same position of the kidneys, and the same position of the intestines in a long slender body that we have in a short thick body. Neither can we have the same degree of functional ca- pacity and functional activity in all individuals. There has been too much of a tendency to try to measure all individuals by the same standard. In examination of the chest a low diaphragm in one patient would not be a low diaphragm in another. The heart must assume an entirely different posi- tion in a long chest from what it does in a short chest. "We cannot judge the position of the abdominal viscera with relation to the umbilicus in all individuals. The examiner must bear in mind, therefore, that the organs must fit in according to the size and shape of the cavity in which they are placed. In this way only can he learn departures from the normal. Clinicians must also bear in mind that there is no normal functional activity for all individuals. In discussing the functional activity of the gastrointestinal tract, observers tell us that the stomach should be empty in six hours; consequently, we fix in our mind that anything short of six hours is too rapid, and anything later than six hours is too slow. Such is erroneous. An individual with a stomach in a high state of functional activity and strong musculature may empty this organ in less than six hours, without being looked upon as having hypermotility. On the other hand, a person with a less degree of functional activity with less muscular strength, might require longer than six hours and still not suffer from hypomotility. Our conception of the normal must be altered to suit the phy- sical and functional capacity of the individual. To simplify matters, however, individuals may be classified in certain groups in which the shape, relationship, and functional capacity of organs may be inferred from the physical form and degree of nerve stability of the individual. Fig. 65A. — Sagittal section through the body showing the thickness of the soft struc- tures covering the apex from which may be inferred the importance of the increased tone (spasm) or degeneration upon the findings on palpation, percussion, and auscultation. Anterior view. (Corning.) M. trapezius. M. omohyoideus. M. supraspinatus. A. mibelavia. Costa I. Clavicula. Plane or Manubrium Sterni. Scapula. M. subscapular^. LobuB Buperior pulmonis. Incisura interlobaris. M. pectoralis major. Lobus medius pulmonis. Transthoracic Plane, Lobus inferior pulmonis. Diaphragm Transfyloric Plane. Right kidney. Vesica fellea. (Gallbladder.) Flexura coli dextra. (Hepatic flexure. Musculature of abdominal parietes. Colon transversum. Trans-tubercular Plane, Tntestinum cecum. M. gluteus medius. Intestinuiii tenue. M. iliaeus. M. gluteus minimus. Caput fehioris. H. gllitwufl inaximus. M. iliopsoas. V. femoralis. Fig. 6SB. — Section through body 6 cm. to the right of the median plane, viewed from the right. Showing the importance of the soft tissues as influencing physical examination of different areas of the chest. (Berry.) Costa I. Scapula. • Manubrium Sterna. Lobus superior pulmonis.- IVriiurdium., Ventriculus sinister. Transthoracic Plane. Lobus inferior pulmonis, Diaphragina. Pars cardiaca vehtriculi. (Stomach.) Glanclula suprarenalis. Left kidney. .' Corpus pancreatis„ TRANSPYI.ORIC PLANE. Pars pylorica ventriculi. (Stomach.) Flexura duodenojejunalis. M. sacrospinal is. (Erector spince, transyersus lumbar vertebra, 51. psoas major. Musculature of abdominal parietes. Transtubercular Plane. Pars lateralis ossis sacri. A. iliaca comimtnis sinistra. V. iliaca Intestinum tenue. M. piriformis. A. iliaca externa sinistra. Ramus superior ossis pubis. M. obturator internus. PLANE OK SYMPHYSIS OsSIUM PUBIS. Membrana obturatoria. M. obturator externus. M. glxitieus maxinius. Ramus inferior ossis isehii. Adductor musculature. Fig. 65C. — Section through body 6 cm. to the left of the median plane viewed from the right. Showing the importance of the soft tissues as influencing physical examination of different areas of the chest. (Berry.) VARIATION OF VISCERAL FORMS AND HABITUS 335 These facts have been particularly emphasized by the splendid original work of Dr. R. Walter Mills, 'of St. Louis. 3 Owing to the extremely great importance of this subject for all practi- tioners of internal medicine, I wish to append the following orig- inal manuscript prepared especially for this monograph by him. THE RELATION OF VISCERAL FORM, TOPOGRAPHY AND FUNCTION TO THE GENERAL PHYSIQUE, WITH A CLASSIFICATION OF TYPES. By R. Walter Mills, M.D. If by means of the x-ray any considerable number of subjects are studied with regard to the topography of their thoracic and abdominal viscera the factor of individual variation becomes so evident as to make the futility of any single topographical stand- ard exceedingly apparent. The massive body of a heavy power- ful man houses a heart so different in outline from that of a slender woman of less than half his height, as to make them ap- pear almost as different organs. In the same way the general outline of the lung fields, the silhouette of the diaphragm, and the form and position of the abdominal viscera vary widely in extremes. If a series of subjects are so studied as to graphically and accurately reproduce the visceral outlines in that of the bodily figure, certain constancies as to relationship between visceral forms and position and the general physique become apparent; for instance, that a certain type of powerful massive individual always houses a heart and lung fields of characteristic outline, and that such are never normally found in other bodily types. If the above conception be true, there must be controlling fac- tors governing such relationship. It would seem that there are such factors. First and chiefly the essential individual skeletal architecture. The subject of massive osseous plan presents a thoracic cage capacious, deep in its anteroposterior dimensions, wide in its lower lateral, and relatively short as compared to 'Observations on Duodenal Ulcer with Special Reference to Its X-Ray Diagnosis, In- terstate Medical Journal, vol. xxiii, no. 4, 1916. 336 PHYSICAL, EXAMINATION OF ORGANS OF THORAX other types in its longitudinal axis. This latter is influenced by the arrangement of the abdominal regional capacities as such a subject has a high digestive plant in turn due to a relatively small pelvic capacity and considerable space occupying abdom- inal fat. A chest of such fixed regional capacities can only house lungs of certain form. The second determining factor in the relationship of visceral topography to bodily habitus is variation in the muscular tonus of different persons. By tonus we understand that inherent resilience possessed in varying degrees by all living muscular tissue. The muscular tonus of the alimentary viscera is a chief factor in giving them their form; it seems highly prob- able that the form of the heart in like manner may be in- fluenced by the tonus of its musculature. The tonus of the skeletal muscles and intimately associated with it their degree of muscular strength contributes to visceral form by influencing the form of the thoracic and abdominal cavities. A skeletal musculature of a high degree of tonus and strength makes for integrity of the general static poise ; hence there is less tendency to spinal curvature, figure collapse, and postural abnormalities. Again, a well-developed belly musculature is a considerable fac- tor in influencing the form of the abdominal and secondarily, the thoracic viscera. The degree of nutrition plays a role in determining the form of the viscera; where poor, the abdominal viscera are lacking a considerable support in the way of intra-abdominal fat, and occupy a lower position than in well-nourished subjects because the pelvis is more roomy. In turn the upper abdomen being of lesser content is smaller and the form of lung fields and heart consequently influenced being of longer longitudinal di- mensions. The degree of nutrition furthermore modifies visceral form in overnourished subjects through its influence on static conditions and the form of the abdomen. A heavy pendant ab- domen results in a somewhat lower position of the abdominal viscera than is normal for that particular subject judged by the general skeletal type with consequent influence upon the form of the thoracic viscera. The physiological needs of the individual influence the form of the viscera. In one of robust and heavy figure, FACTORS INFLUENCING VISCERAL FORM AND TOPOGRAPHY 337 the heart must serve greater demands and is consequently larger and of a form resulting from a heavier cardiac muscular development. The abdominal viscera having to accommodate and digest a larger amount of food proportional to the metabolic needs of the individual are of a form favorable to a more rapid alimentary motility than occurs in slender persons. All factors influencing bodily and consequently visceral form act in varying degrees in the individual case and frequently at- tain an extraordinary complexity in the determination of the final visceral type and arrangement. On the other hand, one factor may be so dominant as to permit of but little change from the essential plan even though all others be greatly modified; for example, a subject may be primarily of so massive and powerful a physique that no alteration in those other factors usually influencing visceral form serves to change the plan. Muscular tonus and strength may be decreased through debility, great loss of weight occur, and still not greatly alter that essen- tial visceral type and arrangement characteristic of such phy- sique. In that other extreme of habitus, the congenital type having normally a pelvic digestive plant, long gracile thorax, pendant heart and poor muscular tonus, no increase in fat or artificially developed musculature, no improvement in general well being serves to alter the essential stigmata of such type. It is in intermediate types of physique that the balance between the various factors resulting in the individual visceral topography are most delicately balanced, so that a marked loss in the in- tegrity of one factor often results in distinct change in form and position. A man may be of average build, strength and nutri- tion ; in him a marked deficiency in alimentary tonus may result in distinctly different alimentary outlines from what his general physique would lead us to anticipate. From what has been said, it may be gathered that the position is here taken that there is no single type of visceral form or position that may be considered normal, and that all others not corresponding thereto are abnormal. We may no more elect one normal visceral standard than we may elect one individual's physique as a standard for all persons. Eather we must hold that innumerable types of physique, visceral form and topography occur as a rule representing normal conditions and that an ab- 338 PHYSICAL EXAMINATION OF ORGANS OF THORAX normal status only exists when there is a gross departure from the essential bodily plan of that given individual as judged by standards established by studies of large numbers of subjects of similar type. In addition to great variation in the form and position of the viscera any extended observations of different subjects will show an equally wide variation in certain physiological processes ; perhaps the most striking being difference in the degree of vis- ceral tonus. Here too a relationship will be found to exist be- tween the general bodily habitus and the degree of tonus. In those of a certain type of powerful physique, the degree of vis- ceral tonus will be found to be great, while in those of an oppo- site type — asthenics — "congenital enteroptotics, " it is poorest. There are before us certain considerations: First, an infinite variation in bodily physique, visceral forms and in certain phys- iological processes. The presence in this great series of varia- tions of certain dominant types of physique and visceral topog- raphy also well-marked degrees of certain physiological pro- cesses. A constancy of relationship between certain types of physique, certain visceral forms and degrees of physiological manifestations is also evident. Second, a very evident need for more accurate standards by which departures from normal con- ditions whether morphological, topographical or physiological may be judged in the given case. This for diagnostic ends and for purposes of study. A need that it seems perfectly evident can not be subserved by selecting one type as normal and con- sidering all other types — consequently a majority of all per- sons — as abnormal. On the other hand it is obviously impracticable to have an individual, though in many ways ideal, standard of anatomy and physiology for each person. Third, the possibility that failing both a single standard for all and an individual stand- ard for each one, we may through a classification of types as to physique and their parallel visceral peculiarities best serve our ends. This we believe is practical and while a difficult matter on account of the amazing complexity in which different character- istics are often present in the same individual, offers us a basis for further study that is more satisfactory and hopeful than our former one type standard. An investigation of hundreds of individuals in whom the vis- HYPERSTHENIC HABITUS 339 ceral plan has been graphically recorded in its relation to bodily contour, has shown that in two extremes the relationship of habitus to visceral form, position, tonus and motility, is a con- stant. Since the question of chest topography is chiefly of in- terest here, special attention will be given it though it must be emphasized that both thoracic and abdominal topographies and forms are commonly characteristic of certain types of habitus and consequently they bear to each other a definite relationship. In the following descriptions of topographical relations the in- dividual is considered as in the standing position with the stomach filled to the same degree as after the standard bismuth meal. The first of these two dominant types in which the general physical and visceral peculiarities are dominantly characteristic has been classified as hypersthenic (Fig. 66). Subjects of this type are of the most powerful physique and usually very heavy. The body framework is exceedingly massive, the thorax deep anteroposteriorly, wide in its lower lateral diameters and short longitudinally. The costal arch is so obtuse as to be sometimes almost a straight line, giving the figure a peculiar gorilla-like appearance. The pelvis is comparatively small. Corresponding to the form of the thorax, the lung fields are broad at the base, the general direction of their lower borders approaching the horizontal. The lung fields contract markedly from base to apex giving the combined lung fields the form of a truncate pyramid. The apices are small and extend but little above the clavicles, less so than in any other type. The form of the heart being very characteristic in the hypersthenic, influences the outline of the lungs, especially the left. The heart is peculiar in that it occu- pies an almost transverse position. It seems largely below the silhouette of the diaphragm, giving an appearance of being half submerged. Often the outline of the left ventricle is almost a continuation of the lower border of the left lung field. The out- line of the aortic arcus as silhouetted by the x-ray is short and broad, and the shadow of its apex projects less to the left than in less sthenic types. As viewed from the front the lung area ap- pears smaller than in other types, only apparently so as the lungs are much deeper than in persons of slender habit and their vol- ume is consequently in keeping with the size and weight of the body. Owing to the short thorax and the long abdomen charac- 340 PHYSICAL EXAMINATION OF ORGANS OF THORAX teristic of the hypersthenic habitus one of the most peculiar fea- tures of the type is the very high digestive plant, the stomach be- ing almost thoracic and the intestines especially high in position. The visceral tonus is invariably of the highest degree, stomach, small intestine, and colon being equally striking as to their hyper- tonicity. The stomach is of Schlesinger 's hypertonic form or Holzknecht's bull-horn type. The pylorus is the lowest or nearly the lowest part of the stomach. The small intestine is high in the abdomen and equally characteristic as to its hypertonicity which is shown especially by the narrow worm-like outline of the loops of ileum in contradistinction to the broad more or less regular shadows of the ileum in subjects of poor visceral tonus. The colon is very high in position, the cecum being well above the iliac basin, even with the patient standing. The transverse colon is horizontal. The descending colon is long owing to the high position of the intestines and more nearly straight in its entirety than in other types. Visceral hypertonicity characteristic of hypersthenics is possibly most strikingly shown in the multiplic- ity of the colonic haustrge and their sharp and deep demarcation. Alimentary motility is faster in the hypersthenic than in any other type. The contrast meal pours from the stomach immedi- ately on ingestion. Small intestinal and colonic motilities are commensurably rapid, the contrast substance being frequently passed per rectum within twelve hours. Such subjects charac- teristically defecate two or more times in the twenty-four hours. The pure type is rare. I have seen less than a dozen in x-ray type studies of some two thousand subjects — I have never seen a woman of pure hypersthenic habitus though a few have been observed that approached it. Such women are far more mascu- line in their general bodily physical characteristics than are many men. In order to best appreciate variations in type both of physique and topography, it will be best to consider next that habitus which is the antithesis of the hypersthenic, the second dominant type the asthenic (Fig. 67). The asthenic type occurs at the other end of the scale in a series of types representing grada- tions between extremes. Stiller immortalized himself by his con- ception of this type, his "Asthenia universalis congenita," though his work has had to await the x-ray for its fullest appre- ASTHENIC HABITUS 341 eiation. Persons of this type are most commonly women of frail slender build having a delicate bony structure, feeble muscula- ture, and but little body fat. The thorax is long and gracile, the intercostal angle is narrow and the ensiform absent or rudimen- tary. The pelvis is flat and capacious. The most striking and essential characteristic of the asthenic is the marked dispropor- tion between the great capacity of the pelvis and the limited capacity of the upper abdomen and lower thorax, this of neces- sity determining a pelvic digestive plant and a thoracic topogra- phy corresponding thereto in its disproportionately long longi- tudinal dimensions as compared to its short lateral distances. How great this disproportion between the pelvic capacity and that of the upper abdomen may be appreciated by considering other factors. The pelvis of a woman of pure asthenic type is often far broader and more capacious than that of a woman ap- proaching the hypersthenic type, this though the lower thorax of the latter is twice the capacity of that of the former and the body weight frequently twice as much. The form of the lung fields is markedly influenced by the asthenic habitus; they are relatively broad in their upper zones and narrow in their lower, in contradistinction to those of the hypersthenic. The diaphragm slopes sharply downward to each side though very frequently this is less marked owing to general static changes resulting in a degree of figure collapse. The lung apices are large and extend well above the clavicles. The lung fields appear large for the individual probably because anteroposteriorly shallow and on account of the meager fat and muscular clothing of the body frame. The heart is of that peculiar form described as drop heart being narrow and pendant. It is median in position its long axis being in that of the longitudinal axis of the body. In general its position is well above the diaphragm. The aortic outline is long narrow and above is deflected to the left as a club- shaped terminal. In keeping with the relatively great capacity of the lower abdomen, the digestive plant is low in position. The stomach is largely pelvic as are the ileum and colon. The form of the various portions of the digestive tube is characteristic and some portions bear hardly a resemblance to the similar structures of the hypersthenic. The stomach appears as a pendant sac and is of that peculiar form designated by Schlesinger as atonio. 342 PHYSICAL EXAMINATION OF ORGANS OF THORAX The ileum is capacious and the colon is characterized by its large cecum and the coarseness of its haustration. Equally striking and constant with the differences in position and form of the viscera in the asthenic and hypersthenic is the difference in the Fig. 66. — The hypersthenic habitus, a dominant type. Essential characteristics are mas- sive figure, short deep capacious thorax, very obtuse intercostal angle, with wide well- developed ensiform. Lung fields very wide at base and narrowing rapidly to their apices. A heart whose longitudinal axis is almost horizontal. A long abdomen relatively more capacious in its upper zones and housing a digestive plant of very high position. The highest degree of visceral tonus and the most rapid alimentary motility of any type are other characteristics. (Mills.) VISCERAL ATONY CHARACTERISTIC OF THE ASTHENIC 343 degree of alimentary tonus. The essential tonal attribute of the asthenic is atony. The parts of the alimentary tube in the asthenic are never endowed with sufficient muscular tonus to support their contents. The contractility of the sphincters is also poor as shown by the ease with which the pylorus may be Fig. 67. — The asthenic habitus, a dominant type. Essential characteristics are frail, slender figure, a great disproportion between the capacious pelvis and wide hips and narrow upper abdomen and lower thorax, a very narrow intercostal angle with no or only a rudi- mentary ensiform is constant. The lung fields are relatively narrow in their lower zones and wide in their upper. The diaphragm slopes sharply downward to both sides from the median line. The heart is central in position, its long axis being approximately in that of the body median line. It is of characteristic pendant form and its shadow is but little covered by the silhouette of the diaphragm. Stomach and intestines are very low in posi- tion, conforming to the regional capacities of the abdomen. The form of the stomach and colon is very characteristic. The degree of alimentary tonus is the poorest and gastro- intestinal motility the slowest of any type. (Mills.) 344 PHYSICAL EXAMINATION OF ORGANS OF THORAX overcome by manual manipulation as shown by the fluoroscope and the poor tonus of the rectal sphincter. Alimentary motility is slower in the asthenic than in any other type. The stomach not infrequently does not completely empty within six hours after a standard bismuth meal, this without organic cause for such. The motility of small and large intestine is commensurably slow. The comparison of asthenic and hypersthenic might be continued to show an antithesis in almost every physical physio- logical and psychical attribute. In the assumption of such an idea as of a multiplicity of nor- mal anatomical and physiological types one may ask on what basis such a conception rests, a conception opposing the generally accepted idea of a single normal type with variations from such, for instance, low position of the viscera representing acquired pathological conditions, an idea that has been accepted since the days of Glenard and emphasized by the writings of Ewald, Wol- kow and even Stiller, who while accurately describing the type designated by him the asthenic, held that such type is peculiar in that it predisposed to visceroptosis. Of any single species of organism man shows the widest varia- ion in his visible characteristics. This owing to his wide geo- graphic distribution, to great difference in his manner of living and most to the advent of reason as a modifier of those natural evolutionary processes that have resulted in the creation of fixed species among the lower animals who vary but little from their species type and within limited bounds. There is frequently greater physical variation among the children of the same parents than in different species among the lower animals. One has but to suggest the difference in faces and hands or of the ratio of body height to weight. Man is not a species of fixed physical char- acteristics varying within narrow limits. It does not seem rea- sonable that the viscera housed in bodies varying so widely must be of one type as to form and arrangement to be considered nor- mal. Again, certain bodily structures whose form could not pos- sibly be modified by any acquired characteristic such as viscerop- tosis, are as characteristic of certain types associated with low posi- tion of stomach and intestine as are other bodily peculiarities that might be interpreted as the result of such ptosis. For instance the form and relative capacity of the pelvis in the asthenic type JUSTIFICATION OF A TYPE ANATOMY AND PHYSIOLOGY 345 could not possibly be changed by any degree of splanchnoptosis, yet the proportions and structure of the pelvis are absolutely typical of such habitus. It is always possible under usual con- ditions to anticipate the peculiar form, and low position of the stomach of an asthenic from a radiograph of his pelvis alone. Further it is difficult to reconcile ourselves to the idea of a con- dition being essentially pathologic that exists in so great a pro- portion of healthy subjects. It is true that asthenics are of an inferior type; that they are not strong physically; that they are nervously unstable, fatigable and prone to digestive disorders. On the other hand, every walk of life is crowded with those of this type who never had a digestive disturbance and who fre- quently show a surprising endurance and capacity for work. It is not meant to imply that ptosis of the viscera does not occur, but the position is taken that before such is assumed there must be a departure from that abdominal topography to which the in- dividual is entitled on the basis of his general structural type. On the same basis we may assume with equal propriety and utilize diagnostically an elevation of the viscera when the posi- tion of such is higher than the type standard for that particular person. A scirrhus carcinoma of the stomach in an asthenic re- sults in a stomach of higher position than we should consider normal on the basis of physique. On the other hand if a benign pyloric stenosis with resulting atony occurs in a hypersthenic subject the stomach may be low for that particular type of individual though still well above the umbilicus. One of the strongest arguments in favor of a type anat- omy is that certain persons, essentially asthenic yet hav- ing none of those physical peculiarities supposed to cause ptosis still have abdominal viscera of low position and charac- teristic asthenic form. A number of studies of women have been made who present the essential structural characteristics of the asthenic yet who weigh as much as one hundred and eighty pounds, are fairly muscular, and of good static poise. This vis- ceral topography is purely asthenic, the stomach and intestines being low in position, of a relatively poor degree of tonus, and of that characteristic form typical of the ''congenital enteroptotic. " It is not contended that the relationship between bodily habitus and visceral form, position, tonus and motility is always constant. 346 PHYSICAL EXAMINATION OF ORGANS OF THORAX Not infrequent variations occur but it is held that in extremes of type this relationship is positive and in intermediate types it holds to a degree that makes a type anatomy and physiology the most hopeful possibility of escape from the chaos that has re- sulted from our present one type standard. Fig. 68. — The sthenic habitus, a major type. The characteristics of this type are very similar to those of the hypersthenic, but differ in that they are all less marked than in that type (Fig. 66). Thus the general physique, while as a rule heavy and powerful, lacks the peculiar massiveness of the hypersthenic. In the sthenic the thorax is short and wide, the intercostal angle of about ninety degrees. The lung fields are relatively wide in their lower zones. The longitudinal diameter of the heart is somewhat transverse. The abdomen is rather long the alimentary viscera high in position. Gastrointestinal motility is fast and stomach and intestinal tonus of high degree. (Mills.) INTERMEDIATE TYPES 347 The principle of type topography has been illustrated by the description of the two most widely varying types, the hypersthenic and asthenic. Between these two occur an infinite variety of physical forms and visceral plans. Among these are two types Fig. 69. — The hyposthenic habitus, a major type. Essentially an intermediate habitus, numerically common. It is the most difficult type to classify, as all _ characteristics approach a mean. In general, the structural characteristics are sthenic, while the visceral arrangement is more that of the asthenic. Hyposthenics also most frequently resemble the asthenic in their lack of robustness. The thorax is moderately long the intercostal angle narrow, usually about forty degrees, with the ensiform rudimentary or lacking. The lung fields are intermediate in their general proportion between those of the sthenic and asthenic types. The heart resembles that of the asthenic. Frequently it is of quite pen- dant form. The stomach is moderately low in position and the intestines occupy a relative position. Visceral tonus is rather poor on the whole though of higher degree than in the asthenic. Alimentary motility is of average rate. (Mills.) 348 PHYSICAL EXAMINATION OF ORGANS OF THORAX that seem constant enough to afford a basis of type classifica- tion. The first is the sthenic (Fig. 68) and the second the hypo- sthenic (Fig. 69). As the names imply, they are types in which sthenic characteristics are dominant though differing in their degree. Our classification may be now stated as a division into four major types arranged in gradations: hypersthenic (Fig. Fig. 70. — The hypersthenic to sthenic habitus, a sub-type. In this habitus physical and visceral characteristics are essentially hypersthenic (Fig. 66) though not as markedly so as in that type but tend somewhat to the next lower form, the sthenic (.Fig. 68). Thus the thorax has not quite the depth of the hypersthenic and the intercostal angle is less obtuse. The stomach is not quite so extreme in form and position; other characteristics are rela- tively modified. (Mills.) NECESSITY OF SUB-TYPES 349 66), sthenic (Fig. 68), hyposthenic (Fig. 69), and asthenic (Fig. 67). Variation in the physique and visceral topography of dif- ferent subjects is so great that this classification is not sufficient- ly elastic to lend itself to practical use. We must have finer subdivision of these types. To meet this requirement every sub- ject is primarily classified as of that one of the above four divi- sions that his essential bodily peculiarities assign him. Should his general habitus be purely that of one of these types, no Fig. 71. — Sthenic to hypersthenic habitus, a sub-type. Here the essential characteristics are those of the sthenic (Fig. 68) but somewhat more suggestive of the hypersthenic (Fig. 66) than is the case in the pure sthenic. The thorax is a little shorter, the inter- costal angle somewhat wider and the whole figure more massive than in the sthenic. Visceral form, position, and other peculiarities are similarly modified. (Mills.) 350 PHYSICAL EXAMINATION OF ORGANS OP THORAX further classification is necessary. If however he be essentially of one of them yet present other characteristics suggesting the group above or below him, he is classified as primarily of that one of the four major types that he most resembles yet tending to another. We thus have six sub-types (Figs. 70, 71, 72, 73, 74, and 75). An individual may be essentially sthenic yet tend to Fig. 72.— Sthenic to hyposthenic habitus, a sub-type. While the general structure is here sthenic (Fig. 68) there is a tendency to the hyposthenic (Fig. 69). This is shown by a less marked robustness, a longer thorax and shorter abdomen than in the pure sthenic. The visceral topography and other peculiarities are proportionately intermediate. (Mills.) CLASSIFICATION OF SUB-TYPES 351 the hypersthenic in which instance he is classified as "sthenic to hypersthenic" (Fig. 71), or he may be dominantly a sthenic yet tend down the scale to the hyposthenic. He would then be classi- fied as sthenic to hyposthenic (Fig. 72). This classification is partly the result of an effort to build, as is fitting, on certain Fig. 73. — The hyposthenic to sthenic habitus, a sub-type. In this sub-form the char- acteristics of the hyposthenic (Fig. 69) are dominant though the figure and alimentary peculiarities are somewhat more sthenic (Fig. 68) than in the pure hyposthenic. Thus the intercostal angle is wider, the position of the stomach higher and its tonus more marked. (Mills.) 352 PHYSICAL EXAMINATION OF ORGANS OF THORAX work that lias already been recognized, namely Stiller 's descrip- tion of his asthenic and sthenic types and Schlesinger 's classifi- cation of stomach forms into hypertonic, orthotonic, hypotonic, and atonic. This latter classification lends itself as a parallel to the above classification. Schlesinger 's hypertonic stomach is Fig. 74, — The hypersthenic to asthenic habitus, a sub-type. While essentially hypersthenic (Fig. 69) there is considerable suggestion of the asthenic (Fig. 67) in this type. This is shown in the long thorax with somewhat narrow intercostal angle but especially by the relatively wide pelvis, which, with the vertical heart and moderately low position of the somewhat atonic abdominal viscera, distinctly suggest the asthenic. (Mills.) RELATION OF STOMACH TYPES TO HABITUS 353 essentially the stomach of the hypersthenic (Fig. 66) his atonic stomach that of the asthenic (Fig. 67). The orthotonic stomach corresponds to the sthenic (Fig. 68), though less exactly than do the other stomach forms to their parallel habits. The hypo- tonic stomach is the stomach of the hyposthenic (Fig. 69). The classification proposed may be used as a division of all subjects into two types in which sthenic or asthenic characteristics are dominant, as a division into four major types, or may include a classification Fig. 75. — The asthenic to hyposthenic habitus, a sub-type. Essentially characteristic are those of the asthenic (Fig. 67) though there is a suggestion of the hyposthenic (Fig. 69) in the only moderately wide pelvis and the lack of that extremely low position of the stomach found in the pure asthenic. (Mills.) 354 PHYSICAL EXAMINATION OF ORGANS OF THORAX of sub-types. Our classification may be illustrated by the following schema : Hypersthenic tending to sthenic Sthenic Sthenic tending to tending to hypersthenic hyposthenic Hyposthenic tending to sthenic Groups in which sthenic characteristics are dominant. Dominant Types Hypersthenic Asthenic Major Types Hypersthenic Sthenic Hyposthenic Asthenic Sub-Types Hyposthenic tending to asthenic Asthenic tending to hyposthenic Groups in which asthenic characteristics are dom- inant. The sthenic type (Fig. 68) may be best described as one in which the peculiarities of that type heretofore described as hypersthenic are present but in a less marked degree — "Sthenic" subjects are heavy powerful individuals of generous body archi- tecture, deep chests, wide intercostal angle, high digestive plant, and having more than an average degree of visceral tonus. They are a common type. Most of the heavy robust persons of one's acquaintance are sthenics. The lung fields of the sthenic re- semble those of the hypersthenic quite closely in that they are also relatively wider at the base and narrower in their upper zones. Their longitudinal dimensions are short, less so than in the hypersthenic but more so than in other types. The di- aphragm approaches the horizontal. The heart is less transverse than in hypersthenics but more so than in lower types. It does not appear as submerged in the diaphragmatic contour as in the pure hypersthenic. The intercostal angle is obtuse, usually about ninety degrees. The ensiform is well developed. The ali- mentary tract is high in position. The stomach is entirely or nearly entirely above the umbilicus, or perhaps better, above HYPOSTHENIC HABITUS 355 the level of the anterior iliac spines. The transverse colon is, as a rule, above the same landmarks (standing position). Other parts of the intestines occupy a proportionately high position. Visceral tonicity is of a high degree. Alimentary motility is fast. The remaining type is the hyposthenic (Fig. 69). Subjects of this type are the most difficult of classification of any type be- cause while the general bodily characteristics are more sthenic than asthenic, the chest and visceral arrangement in a large pro- portion of cases resembles that of the asthenic in the form of the lung field, general direction of heart axis and low position of the abdominal viscera. However, while thoracic and abdom- inal topographies resemble those of the asthenic, the visceral forms are not those peculiar to that type (Figs. 69 and 67). Those of hyposthenic type are generally somewhat frail in phy- sique, in fact many women of this type would at first sight seem to be of asthenic habitus. They lack, however, certain pecul- iarities of such type especially the disproportionately wide and capacious pelvis. Each lung field is more vertical and wide in its upper zone than in those types in which sthenic charac- teristics are marked. The diaphragm is quite sloping. The heart approaches a vertical position, often has quite the pecul- iarities of the hanging heart. The intercostal angle is narrow; usually less than ninety degrees; the ensiform rudimentary or lacking. The alimentary viscera are rather low in position, a considerable part of the stomach being below the umbilicus. The intestines occupy a relative position; alimentary tonus is of but fair degree and motility of average or less than average rate. The various types are better appreciated by the accompanying diagrams, each of which is the accurate scale record of an in- dividual, than by description. It is better at first to accustom oneself to classifying all subjects into one of the four major types without attempting to use the sub-types. The recognition of the different types is a matter of experience and practice and is often difficult. In some cases a subject is almost impossible of classification owing to a complexity of char- acteristics; the thorax may be of one type, the abdomen and visceral topography of another; such are, however, very much 356 PHYSICAL EXAMINATION OF ORGANS OF THORAX in the minority. A most confusing type is one in which the gen- eral habitus is one of the intermediate types, yet the degree of visceral tonus owing probably to an unusual balance in the au- tonomic nervous system is extreme or deficient giving the differ- ent parts of the alimentary tract the position and form of a higher or lower type. To summarize, physical and visceral types are best recog- nized by an appreciation of their extremes : the hypersthenic and asthenic, all other types represent intergradations between these two. Secondly, by the recognition of two main intermediate types, the sthenic and hyposthenic, and thirdly, by variations of these four types in the form of certain sub types primarily one of the four main types but tending to the next higher or lower type in the scale. CHAPTER XIV. THE DIAGNOSIS OF EARLY PULMONARY TUBERCU- LOSIS: HISTORY AND CLINICAL SYMPTOMS. Meaning" of Early Diagnosis. — There are many misconcep- tions regarding the early diagnosis of tuberculosis. These have been largely unavoidable up to the present time, because our pic- ture of this early condition has been based on a faulty concep- tion of the disease. What we mean by early diagnosis of tuberculosis may noFbe, in fact rarely is, a diagnosis made soon after the bacilli have en- tered the body. It may be months, often years, after the original infection has occurred that the patient observes the first symp- toms and presents himself for examination. What we have been hitherto considering as early tuberculosis, considered from the standpoint of the time when infection occurs, is really late tuber- culosis in most instances. It is a condition in the life history of the disease which represents not a primary invasion but an ex- tension to new tissue ; and, often, a renewed activity in one of these extensions. Tuberculosis is primarily a disease of the lymphatic system, the time of the infection being childhood (see page 84). No matter where or how bacilli gain entrance to the body they pass into the lymphatic channels and are screened out by the lym- phatic glands, those of the mediastinum most frequently. This constitutes the truly incipient stage of tuberculosis. These early mediastinal infections are found, as a rule, postmortem; but they may be inferred by a positive tuberculin test when infection of other organs has been eliminated. Infection of the glands is rarely physically demonstrable until the disease has existed for some time and the bacilli, finding themselves suited to the new soil, have already multiplied and produced a somewhat ad- vanced pathological process. There is a greater similarity between tuberculosis and syphilis 358 DIAGNOSIS OP EARLY PULMONARY TUBERCULOSIS than is generally believed. We are told how syphilis may sim- ulate so many other diseases in its clinical picture. Tubercu- losis does the same, as I shall describe when discussing clinical symptoms. Syphilis has been divided into the primary, sec- ondary and tertiary stage. Tuberculosis may also be so divided, lianke, of Munich, likens the early lymphatic form of tubercu- losis, the invasion, to the primary stage of syphilis ; the extension to new tissue, — it may be to distant organs such as the lungs, kidneys, bowels, and meninges, — to the second stage of syphilis; and the advanced lesions with their destructive processes and general systemic disturbances to the gummatous or tertiary stage of that disease. This comparison is of more than usual interest to clinicians and at once impresses forcibly upon the medical profession facts which are of paramount importance to a rational understanding and the early detection of tuberculosis, viz. ; that it is a disease of long duration, presenting a varied picture in its pathological aspects at different stages, and presenting a symp- tom-complex, requiring careful study; and, further, that the so- called early diagnoses are diagnoses of conditions which present an advancing process. The problem of the diagnosis of early tuberculosis as recog- nized today, then, is that of detecting the disease in what might be termed the second stage of its development, the stage of in- creased activity as applied to the lymphatic glands or of exten- sion to new tissue, or of any successive increased activity or ex- tension from a previously quiescent focus. Clinical Tuberculosis. — The writer has been in the habit of speaking of the condition just mentioned as clinical tuberculosis in order to differentiate it from the primary infection (the truly incipient tuberculosis) and primary metastasis in the lung, which so often becomes quiescent ; both of which are often spoken of lightly as anatomical tuberculosis. It is well, however, to call attention to the fact that our best opinion today supports the idea that much of the "clinical tuberculosis" is an exten- sion from the so-called anatomical tuberculosis, showing that the latter condition deserves far more consideration at the hands of clinicians than it now receives. RELATION OF CLINICAL DIAGNOSIS TO INFECTION 359 This conception puts new meaning into early diagnosis, and impresses upon clinicians the seriousness of the advanced and advancing condition which we have been wont to consider as an early manifestation. While experience shows that many of those who suffer from clinical tuberculosis will get well, even by the adoption of simple measures, the fact that one-tenth of the hu- man race still dies of this disease is sufficient to demand that clinical tuberculosis be recognized and treated seriously. Relationship of Clinical Diagnosis to Infection. — This shows clearly that if we would understand early diagnosis, it is neces- sary to study infection; to know when it takes place and what occurs when it has taken place. It is not sufficient to know that there is a pathological thickening of the tissues, accompanied by certain signs and symptoms ; it is just as important to know that the cells of the body are changed and sensitized toward further attacks of the tubercle bacillus. If a subsequent inoculation of bacilli takes place, the phenomena which occur as a result of the struggle between the invading bacilli and the invaded organism are not the same as those in the primary infection. If the num- bers of bacilli in the subsequent inoculation are sufficiently large, a recognizable train of symptoms occurs which is due to the struggle between the invading bacilli and the cells of the body which are now endowed with specific defensive powers and the antibodies which the cells produce for the specific purpose of warding off the invasion. If this subsequent inoculation is made experimentally by injecting bacilli into the soft tissues of an animal already tuberculous (Koch's experiment, page 82) a local ulcer forms, the bacilli are cast off, and the regional lymph glands are not even infected. If the superinfection is made through the blood or lymph stream, the bacilli settle somewhere in the tissues; and the reaction (specific cellular reaction) be- tween the tissue cells and the bacilli again shows differently from what it does if it is a primary infection, although the difference may not be so evident as it is when the bacilli are in- jected into the tissues. Many of the bacilli are destroyed; and, while if the numbers are large enough, infection occurs, yet the process assumes a chronic form. In guinea pigs these sub- 360 DIAGNOSIS OF EARLY PULMONARY TUBERCULOSIS sequent infections or superinfections, as they are called experi- mentally, show evidence of cavity formation and other signs of chronicity while the primary inoculation develops acute dis- seminated tuberculosis. The nature of chronic tuberculosis with its tendency to chronicity and cavity formation is probably determined by the specific defensive properties with which the cells are endowed (sensitized condition) and must be thought of as analogous to the phenomena described by Koch in connection with a secondary infection of a previously tuberculous guinea pig. All abortive, as well as chronic forms of tuberculosis, whether of the fibroid, or fibro-ulcerative form, must be looked upon as having this specific tissue reaction as a determining factor. The experimental work which has been done in recent years, when interpreted clinically, goes to show that the most of our instances of clinical tuberculosis are reinfections in the sense that they are infections which have taken place in bodies which have been previously infected. They are not necessarily infections by new bacilli coming from some source outside of the body of the individual, but most probably extensions from a focus within, which may have been the result of a recent infection or one which occurred months or years previously (see page 85). The probability of this is established by pathological and clinical evi- dence both of which go to show that the infection of the human race with tubercle bacilli is almost universal by the time the fifteenth year has been reached (see pages 78 and 100). The phenomena which present themselves at the time of the reinfection vary and probably depend upon the degree of sen- sitization (specific cellular defense) present, the numbers and virulence of the invading bacilli, the suitability of the soil as a culture medium, and the character of the tissues invaded. Thus we may explain the varied nature of the symptoms and the dif- ferences in the pathological conditions which we have gradu- ally learned to recognize as accompanying the onset of clinical tuberculosis. Thus we may explain the fact that we so often fail in recognizing the early manifestations of clinical tuberculosis. Clinical Diagnosis. — It will be inferred from previous discus- sion that the diagnosis of early clinical tuberculosis takes into CLINICAL DIAGNOSIS 361 consideration two distinct conditions; first, the diagnosis of the disease when it first invades the lung tissues, and, second, the diagnosis of the disease when it is a renewed activity in an old focus of infection which may have been quiescent for a longer or shorter period of time. While these two conditions may pre- sent similar diagnostic data; on the other hand, they may pre- sent data, particularly that which is obtained on physical ex- amination, of a very divergent nature. I will endeavor to make this plain as my discussion proceeds in the following chapters. I shall take up each of the recognized methods of obtaining information and discuss them and the data obtained by them and endeavor to show how the findings vary under different conditions, hoping thus to make clear the application of the measures discussed. There is no stereotyped way of making a diagnosis of early pulmonary tuberculosis. The diagnosis is not always based on the same conditions. It is not based on data derived from any particular procedure, but it is an opinion formed after all avail- able data have been obtained and analyzed. He who attempts to find the same symptoms or the same physical signs in every instance before he will make a diagnosis of early pulmonary tu- berculosis fails to grasp the nature of the process which he is attempting to discover. The patient suffering from early clini- cal tuberculosis usually shows only a few of the many symp- toms which are found accompanying this condition, and these may not be constant. They are now present for a time and then may disappear, giving the patient the idea that they are gone, as described more fully in Chapter XXI. Variability is neces- sarily characteristic of symptoms and signs in this disease because conditions are so varied. This can readily be appreciated from the discussion which has preceded. The diagnosis of early clinical tuberculosis requires time for examination, skill in obtaining the proper data, and judgment in weighing the data when obtained. Family History. — The family history was formerly of first im- portance, because it was thought that tuberculosis was handed down as an inheritance from one generation to another; but now 362 DIAGNOSIS OP EARLY PULMONARY TUBERCULOSIS that we know that this disease is an infection which occurs almost wholly after birth we attribute a different meaning to it. The history of open tuberculosis in a family, if it has offered opportunity for intimate and prolonged association, between the one affected and the patient now under examination, is very important, and especially if this association took place during the early years of the patient's life. The reason why so much im- portance is attached to the intimate association with open tu- berculosis in early childhood is because the closer the contact the greater the danger of infection with large numbers of bacilli ; and, the greater the numbers of bacilli in the infecting inocula- tion, the greater the danger of the disease overcoming the nat- ural defensive powers and assuming serious proportions. While civilized people are universally exposed to tuberculosis, those who associate intimately with it are exposed to the greatest ex- tent. This is illustrated by the statistics of Cohn, in the following table, which show that all children in tuberculous families are infected prior to the fifteenth year, while probably 10 or 15 per cent of those in non-tuberculous families escape. Cohn, cited by Eomer 1 gave the cutaneous tuberculin test to 273 children of tu- berculous parents and found as follows: per cent gave a positive reaction. Of those from 2- 3 years, 66 4- 5 > y 60 6- 7 > ) 77% 8- 9 > > 77 10-11 > ! 80% 12-13 J > 89.9 14 } ) 100 The probability is that the children of tuberculous families also have a greater immunity than those of the non-tuberculous fam- ilies, although a greater per cent of them die of tuberculosis. The assumption on which we base the opinion of greater im- munity is the fact that if these children in tuberculous families withstand the immediate effects of the relatively larger doses of bacilli, their infections so often present abortive and chronic forms of tuberculosis. On the other hand, the greater mortality usually occurs in the acute forms of the disease such as meningitis trailer's Beitrage zur Tuberkulose, vol. xxii, 1912. CLINICAL HISTORY 363 and generalized tuberculosis which occur during the early years of life before specific cellular defense has been obtained. Von Euck has shown that specific resistance to tubercle bacilli is transmitted by the tuberculous mother to her child. What are we to say of the danger of intimate association as it occurs in the family of the tuberculous, particularly in adult life ? Our newer studies of tuberculosis show that there is a high degree of immunity developed against the bacilli by the time adult life is reached. And we are permitted to infer that this is sufficient to protect the individual against all ordinary in- oculations which might come. It is also probable that instances of tuberculosis as we find them in adult life are largely due -to extensions from foci within the body rather than inoculations of bacilli from without. The real danger, however, comes from bacilli entering the tissues in sufficiently large numbers, whether from without or within, to break down the protective immu- nity and cause a new infective process to be set up. The greatest danger of such a thing happening comes when the individual is exposed most intimately to great numbers of bacilli, such as in the family where tuberculosis is present in the advanced destruc- tive stage. Therefore, when the history of association with open tuberculosis in the family is positive, it is the examiner's duty to find out how long such association has existed, how intimate it was and at what period of life it occurred. A continuous in- timate association with one in the advanced open stage of the disease may be of great importance at any age, but it is particu- larly suggestive during the early years of the patient's life. CLINICAL HISTORY. In order to make a diagnosis of clinical tuberculosis early, it is necessary for the examiner to disabuse his mind of the long supposed fact that a tuberculous patient must necessarily be of the phthisical habitus with flat chest, be run down, and be suffering from a low state of vitality. Such a history will be obtained in many cases, but not in all. There are many patients suffering from early clinical tuberculosis who are of robust build, who have been working hard and doing their work easily, and 364 DIAGNOSIS OF EARLY PULMONARY TUBERCULOSIS who show none of the usual stigmata that are assigned to those suffering from this disease. The old teaching that any man may have syphilis has its counterpart in tuberculosis. Any man may have tuberculosis; and, when it is present in its early stage at the time when it is most curable, the patient does not neces- sarily differ in his appearance from other members of society. History of Past Illness. — Most patients who present for exam- ination are suffering from renewed activity in an old focus or from an extension of the disease to new areas. Therefore, it is important to inquire carefully whether the patient at any time during his previous years suffered from similar symptoms. It is not uncommon for the patient, after a little reflection, to re- call previous attacks which were similar; or, to recall other symptoms or attacks which were most probably associated with previous periods of activity in the same or other tuberculous foci. A previous pleurisy, or tuberculous bronchitis, or spitting of blood or fistula is not uncommonly found in the previous history, antedating the present illness from one to twenty years. These attacks are usually characterized by other names, some- times through ignorance and in other instances with intention to deceive. ' ' La grippe, " ' ' bronchitis, " ' ' neurasthenia, " ' ' anemia, ' ' "malaria," "a run-down condition," "intercostal neuralgia," "bleeding from the throat," are terms which are frequently em- ployed in comforting and lulling the patient, who is suffering from early clinical tuberculosis into false security. "We can hardly conceive of anyone having constantly repeated attacks of la grippe; bronchitis which hangs on and comes frequently is always suspicious; neurasthenia demands a diagnosis and has tuberculosis for its etiological factor oftener than is generally believed; malaria should not be confidently assigned as the cause of the general lack of ambition which is found in malarial dis- tricts, for these patients also are subject to tuberculosis and other diseases which cause the same symptoms; a run-down con- dition is suggestive of many things but demands that the phy- sician search until the true cause is found, and if repeated or at all persistent should call for careful search for tuberculosis; intercostal neuralgia is frequently diagnosed when pleurisy of tu- berculous origin is the real condition present; and bleeding from PRESENT ILLNESS 365 the throat is the sedative which throws many people off their guard and allows an early tuberculosis to creep on to an ad- vanced hopeless condition. The history of any of these condi- tions during the past life of a patient is extremely suggestive of previous attacks of active tuberculosis. Slow recovery from other diseases should always excite suspi- cion. Some of the common symptoms of tuberculosis will usually appear if this disease is present and careful physical examination of the chest should be made. The tuberculin test cannot always be relied on under the circumstances. If positive it is valuable ; but if negative, it should be accepted with great reservation (see page 504). Sometimes a definite history of a tuberculous lesion elsewhere in the body, either at the present time or sometime in the past can be obtained. If so, it should not bias the examiner, but cause him to be careful in weighing it along with other evidences. Present Illness. — Hawes 2 rightly emphasizes the importance of asking the patient how long it is since he was per- fectly well. The writer has found this of great importance. The patient does not know when he became ill of the tubercu- lous process because the symptoms at first are so slight that he does not recognize them as making him ill until the early stage has passed. In answer to this question, however, he will often go back weeks or months, and sometimes even years before he finds the time when he really felt well. Some patients will be unable to give any history of previous disease, the active symptoms com- ing on without warning. This sudden explosive type of tubercu- losis is usually overlooked; coming as it does without the usual antecedent history of being run down, and without stomach and nervous manifestations, tuberculosis is not thought of. From the marked rise of temperature present it is often called typhoid, or, if the lung is examined, it is diagnosed as pneumonia or la grippe. Classification of Early Symptoms. — The symptoms belonging to tuberculosis are varied and appear as expressions of disturb- ance in many different structures and organs. When analyzed, 'Early Pulmonary Tuberculosis, William Wood & Company, New York, 1913. 366 DIAGNOSIS OF EARLY PULMONARY TUBERCULOSIS however, all of the twenty or more symptoms can be classified according to their etiology in three groups as follows : Symptoms Due to Symptoms Due to Symptoms Due to Toxemia. Eeflex Cause. Tuberculous Process •per se. Malaise Hoarseness Frequent and protracted Feeling of being run- Tickling in larynx colds down Cough Spitting of blood Lack of endurance Digestive disturbances Pleurisy Loss of strength Loss of weight Sputum Nervous instability. Circulatory disturbances Temperature Digestive disturbances Chest and shoulder pains Loss of weight Flushing of face Increased pulse rate Apparent anemia Night sweats Temperature Blood changes The above classification was first published by the author in January, 1914. 3 Since that time I have made slight changes in the arrangement of the symptoms. By so grouping the symptoms we gain a fuller comprehension of the disease and grasp the situation which presents with greater understanding. General Characteristics of the Toxic Group. — It will be noticed at once that this group of symptoms is expressive of central nerve cell stimulation; that its action is that of general inhibi- tion of function; that the symptoms are expressed widely through the body; and that when taken together, they form the symptom-complex which is particularly expressive of a general nervous discharge through the sympathetic nervous system. It will also be noted that this group of symptoms is not alone char- acteristic of tuberculous toxemia. It can as well be an expression of an infection in a tonsil, the prostate, the fallopian tube, or an intestinal toxemia, or one of the acute toxemias, as of tuber- culosis; consequently, when taken alone is of limited value as diagnostic evidence of the presence of active tuberculosis. The future will reveal more fully the relationship be- tween the toxic state and the secretion from the ductless glands. There is considerable disturbance in glandular functions. The 'Northwest Medicine, Jan., 1914. TOXIC GROUP OF SYMPTOMS 367 adrenal glands are supplied by branches from the splanchnic group of the sympathetics, and respond with increased secretion when the sympathetics are stimulated. Not only do they re- spond to sympathetic stimulation, but the adrenin when circu- lating in the blood stream produces inhibitory action of the same character and in the same organs as that produced by the sym- pathetics. The enlargement of the thyroid, as frequently ob- served during early clinical tuberculosis, suggests that this gland is probably called upon for extra service in the presence of in- fection. This is also supported by its enlargement in the pres- ence of other infections. No matter how the symptoms are produced or what it is that prolongs them, the syndrome of toxemia is that of central stimula- tion plus general discharge through the sympathetic nervous system. The symptoms of this group are those expressive of general inhibition of function on the part of the internal viscera and are prolonged by such states as pain, anxiety, fear, discouragement, disappointment, and general nervous depression. It is impor- tant to bear the influence of the depressive emotions in mind be- cause it, at times, assumes diagnostic importance. Tuberculosis is not a disease which produces a continuous noticeable toxemia in its early stages. It goes through periods of acute activity now and then, which are followed by periods of quiescence. In the early stage, and up to the time that softening begins, clini- cal tuberculosis is in a state of quiescence in by far the greater portion of the time. And even then, unless the area of softening be a large one, the periods of quiescence are relatively long. The symptoms belonging to the toxic group should pass away when the acuteness of the process is over ; or when the body has established an ability to properly counteract these toxic in- fluences. When either of these states has been reached, however, toxemia may still be able to produce its symptom-complex by faulty methods of living on the part of the patient, particularly, overexertion with its attendant increased heat production and autoinoculation. So may the same group of symptoms be pro- longed by such depressive states as pain, anxiety, fear, disap- pointment, and discouragement. 368 DIAGNOSIS OF EARLY PULMONARY TUBERCULOSIS So, it will be seen, that, while this group of symptoms is of great importance in the diagnosis of early active tuberculosis; yet its presence alone is not sufficient to make a diagnosis. It must be accompanied by other symptoms and other signs. It is equally, if not more, important to remark the opposite of this — that active tuberculosis may be present without the presence of the symptoms due to toxemia. It is of greatest importance to early diagnosis that this fact be known. To that end let us recall our pathology. Early pul- monary tuberculosis is an infiltration in the lung tissue. The bacilli are embedded in the tissues and are surrounded by new cells. The process becomes acute only when the bacilli multiply and toxins diffuse into the adjacent tissues. If this process is carried sufficiently far, necrosis takes place. This necrosis does not involve all of the infiltrated tissue, but only a circumscribed portion. When caseation occurs, as it so often does, or when the process has subsided without caseation taking place, the acute symptoms of toxemia disappear; yet the same pathological changes may soon take place in other areas, so we are not justi- fied in looking upon the process in any other manner than as an active one. That this characterization is correct is usually shown by other periods of acute pathological changes with attending toxic symptoms taking place after intervals varying in length from a few days to weeks or months. It is also proved by the fact that the symptoms due to reflex cause, likewise the physical signs due to the same cause, continue to manifest themselves over periods of months after the toxic group of symptoms has dis- appeared. This is well illustrated in the cases described in The Tuberculosis Clinic, Chapter L, Vol. II. SYMPTOMS DUE TO TUBERCLE TOXINS. There is no regularity in the severity of the symptoms based on toxemia because the amount of toxins differ so markedly in different patients and under different conditions. "While this can be more readily seen in advanced cases where we have the two forms, acute caseous tuberculosis and the slow fibro-ulcera- tive form, it is also evident in the early cases. One patient will SYMPTOMS DUE TO TUBERCLE TOXINS 369 suffer greatly and show most of the symptoms mentioned in Group I, and another will hardly realize that he is ill and scarcely complain at all. The latter patient should have the best chance of recovery, for the inhibition of his conservative forces, as produced through stimulation of the sympathetic nervous sys- tem, is less marked, or, as we would naturally say, his disease is less severe. This advantage, however, is too often sacrificed by the delayed diagnosis and unwarranted certainty on the part of the patient, either that he is not ill or that his illness is so slight that he will recover without following a careful routine. Malaise, Nervous Instability, a Feeling of Being Run-down, and Lack of Endurance. — These are common symptoms of ac- tive tuberculosis. They are particularly expressive of the ef- fect of the toxins upon the central nervous system, although they may be caused by all the forces which tend to lower the pa- tient's vitality. When an old tuberculous process becomes ac- tive, or a new infection occurs, patients are very apt to note that they tire more easily than formerly. They suffer from a languor which seems unexplainable. This, at times, almost amounts to an aching. Patients sometimes feel that they do not want to move or be disturbed, and yet they can see no reason for it. Sleep and rest do not refresh them. They seem to have an in- definite feeling due to what is to them an inexplainable cause. It is nothing they can explain, nothing that they can fully grasp ; yet there is a consciousness that something is the matter. Some- times they are taken to be lazy by their friends, and even believe it themselves. When the toxemia is very severe these symptoms are increased. Speaking of languor, Minor well puts it: "The whole body seems filled with tiredness." They note that their disposition is changing. They are irritable and more easily dis- turbed than usual. They often lose ambition and assume a "don't care" attitude. It is such an effort to do things that they find themselves neglecting duties which they have always as- sumed cheerfully. Tasks which were formerly easy are now accomplished with difficulty. A little effort is followed by exhaustion from which recovery is slow. The patient then finds himself in a run-down 370 DIAGNOSIS OF EARLY PULMONARY TUBERCULOSIS condition, a state of low vitality, from which he seems unable to pull himself together. At first the patient does not feel like doing; later he cannot do. His endurance is gone. This state is often diagnosed as neurasthenia. To be sure, neurasthenia is present. But this is not a diagnosis. Neurasthenia has a cause. It is a condition, not a disease. Tuberculosis is very often the cause and should always be thought of, especially if any other signs, such as rise of temperature, and loss of weight, and particu- larly symptoms belonging to the other groups, are present. Gastrointestinal Symptoms. — The toxic symptoms on the part of the gastrointestinal tract in early clinical tuberculosis mani- fest themselves as a general inhibition of action in all the func- tions of the alimentary canal. They are not always constant, nor are they always present in the same degree of severity, yet there is nearly always present some degree of inhibited action upon the functions of the digestive tube. The patient may note a capricious appetite; or the appetite may be absent. At other times he may have little or no noticeable disturbance. During the periods when the toxemia is most acute, however, there is usually at least a slightly coated tongue, a deficiency of gastric and in- testinal juices and a deficiency of gastric and intestinal motil- ity, all of which is an expression of general sympathetic disturb- ance. Loss of iveiglit usually follows this digestive disturbance although it is often difficult to find accurate data on this point as people do not weigh regularly, often not for years. In early tuberculosis this loss only amounts to a few pounds. When there is a loss of fifteen or twenty pounds of weight as a result of the tuberculous process, it indicates that the disease is not early. Such a loss in weight must have a severe pulmonary in- volvement back of it. The infection is either very virulent or widespread, or both; or the inhibited function may be due to depression. It is particularly important for those who are attempting to diagnose early tuberculosis to bear in mind that both men and women attain a maximum weight for their early years when about eighteen or twenty years of age. After holding this a year or two they will fall back five, ten, and sometimes fifteen SYMPTOMS DUE TO TUBERCLE TOXINS 371 pounds and then hold this as their normal weight until after the third decade has been reached. It is very important to bear this in mind when taking histories for it would be manifestly er- roneous to consider this maximum as the normal weight, or this loss as pathological. Other causes for loss of weight must al- ways be considered. This symptom has no value unless accom- panied by others, and at about the age of twenty it may be due to the natural decrease in weight which I have just mentioned. Night Sweats. — In our attempt to offer a physiological explana- tion of the sweating which occurs in tuberculosis, we are con- fronted with the fact that there is still an uncertainty in the minds of physiologists as to the manner in which sweating is produced. There are certain facts which indicate that sweating is at times due to stimulation of the sympathetics, and, again, to stimulation of the greater vagus. It accompanies toxemia, fear, rage, and other symptoms which we know are definitely due to sympathetic stimulation. On the other hand, sweating is found as a symptom of vagus tonus. It is also relieved by atropin, which is the physiological antagonist of the greater vagus. The muscles of the sweat glands receive their innervation from the sympathetics, and when stimulated to contraction, are able to force the sweat from the glands, providing it is already pro- duced; but we do not believe that this is the physiological ex- planation of sweating. There is unquestionably a definite in- nervation of the glands themselves; but whether this comes from the sympathetic or greater vagus divisions of the vegetative system, or both (the latter seems certain from clinical observa- tion), will have to be determined by future study. In tubercu- losis, sweating is an accompaniment of the state of toxemia. Rise in Temperature. — Rise in temperature can either be due to bacillary toxins or to the absorption of other protein from the inflammatory process in the lung itself. It is probably due partly to some increase in metabolic activity resulting in increased heat production, but far more to an interference with the elimina- tion of heat when formed. The discussion of the question of temperature seems more ap- propriate in connection with the study of advanced tubercu- 372 DIAGNOSIS OF EAELY PULMONARY TUBERCULOSIS losis ; yet, in order to make the etiological basis of this symptom clear it should be discussed at this time. That a rise in temperature may be due to the action of bacil- lary toxins as well as to the tuberculous process per se seems evident. To explain the rationale of its production, however, is not so simple. For years my study has led me to look upon the rise of temperature which occurs in infections in general, as a conservative process. 4 It is an index to the reacting powers of the patient. This may be seen in a comparison of the be- havior of the child and the old man toward the same infection, as in pneumonia. The child has a high fever and recovers, the old man exhibits a temperature of 100° to the same infection and succumbs. Crile 5 considers temperature as a part of the protec- tive mechanism against infection. He says: "As to the mechan- ism which produces fever we postulate that it is the same mechan- ism as that which produces muscular activity. Muscular activity is produced by the conversion of latent energy into motion, and fever is produced largely in the muscles by the conversion of latent energy into heat." I will not enter into a free discussion of the cause of fever at this time, having done so more fully in Chapter XXX, Volume II. It is necessary, however, if possible, to make plain the cause of fever, that we may be able to understand the value of this symptom in the early diagnosis of tuberculosis. During the time when tubercle bacilli are multiplying they form toxins which find their way into the blood stream. The inflammation in the lung also causes a certain chemical activity resulting in the ab- sorption of toxic products. The destruction of these toxins is produced by chemical action which results in an increased pro- duction of heat. These toxic products also act upon the central nerve cells. They exert a particular action upon the vasomotor center and produce a general stimulation of the entire sympa- thetic system. As a result, we find vasoconstriction as a part of the syndrome of toxemia. As a result of the extra heat produc- tion, and from this vasoconstriction which is produced by ^Tuberculin in Diagnosis and Treatment, C. V. Mosby Co., St. Louis, 1913, Chapter X. 6 The Origin and Nature of the Emotions, W. B. Saunders Co., Philadelphia, 1915. SYMPTOMS DUE TO TUBERCLE TOXINS 373 toxemia, there results a heat production which is greater than heat elimination, and a consequent rise in temperature. This increase in body heat tends to prevent the multiplica- tion of bacteria which menace the organism and at the same time favors the production of specific defensive substances. Crile postulates that the effect of pain, emotions such as fear and anger, and infections, is all one — that of bringing into activity the latent energy of the body and converting it into active de- fense. The process is the same whether it expresses itself in a motion to escape, or in an attack upon an antagonist, or in the destruction of dangerous toxins by oxidization with an accom- panying rise in the body temperature which inhibits the growth of the invading bacteria from which the toxins arise. This ac- tion takes place through the brain, adrenals, liver, thyroid, and muscles, the organs of the body which are particularly con- cerned in the transformation of latent into active energy. A carefully constructed temperature curve is of great value as an aid to the diagnosis of early clinical tuberculosis during the state of toxemia, but of less value after the toxic state has passed. This cannot be emphasized too strongly. If other sus- picious symptoms are present and a carefully constructed tem- perature curve is characteristic, and a tuberculin test should prove positive, the reaction reaching its maximum early, the diagnosis of probable active clinical tuberculosis should be made even in the absence of physical signs on percussion and auscultation. In order to construct a temperature chart of any diagnostic value, care and exactness must be exercised. A carefully con- structed chart will greatly facilitate the study of temperature. It is very difficult to secure an adequate picture when the tem- peratures are taken and placed in columns on a sheet of paper, but when a graphic chart is made, the picture is grasped at once. The chart should be made of four daily records, and should in- clude both the maximum and minimum for the given patient for the day. It must be recalled that different patients will reach their minimum and maximum temperatures at different times of day. In one the maximum may be ten or eleven o'clock in the morning, though this is rare. Such is most commonly met in those who begin their daily activities early. It might be at two 374 DIAGNOSIS OF EARLY PULMONARY TUBERCULOSIS i 1 ■> S o 3 s r i*iii i i i i i a % n ii s ien In ven this 1 :.'! ! 1 lil!" r''' t« « _, "^ C o rt ■• jj !! ■. ■ i i . . 1 — - a u ° ., ii . i 1 ;. ill | '1 J3 C3 rt 3 : ! ! ; ■ i u <* z . • ' , , T3 Si 2 3 !'-| C^Rc. o p 5" | 1"i o s ■" c ■ ■!' h S8 ° ** ! i.i.l,,:, j I r-4— "-J — " fi u"* S ''I i I ! 5 -^ o ■*-* 1 i ' ' i :il i :! : I i.l 1 ■''■ 'i i : ^ SS^ m j; . ■ ; : ~ ° 5 s !. i ■> i 1 !.!._ L ' " 1 — C5) C &.tl ;h :■ ■ ■:■! h : ' C3 S , ! I i ' i r ■ and ir th s alw mm, Mi 1 il ill | 1; 1 ■ ■ k' ; H 1 - " '1 " 1 — - i ,' i C o g-S V; — « ' i ill: •5 SPcu o ;s j , 1 : » ' P C £— i ; ^fe^t ^j^ ttkr I 1 < w di starti eratu ne be ; — -f i 1 i ■ 4 . ■ j — ■■ 1 1 ' 1 . • K* H i ^6 o « o *^'i _lL 1 T -; t». ^ :..l IS 3 5 m i ''y\^' _j -— i '■■-,' ■ 1 1. r ■ l^: < 1 tl , ... '" i; I 1 ! .4- \) i 1 . 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"So e fl S so S 3 5 1 1; Ijj! fj-i-i-: 4 H: ;| M HI ♦ I \h" i 7°°t &I :!■ i ' ■ I I ':r, -Hpjjwi — r- ^j—~ £R^ " hi K , .!,'' ■'-»,' ,; - ~ . i 1 '• o »- w ° '.I.i it] i ! i i , 1 if':' - | | 6 ] a ' \ i *8§ » § s S S S S s g s] s s s s % s s rk \ £ S Fig. at 7:00 the cor above, time wa RECORD OF EARLY MORNING TEMPERATURE 375 g*c3 C9 % £ £ .5.5 j- "-5 '-a Ih a; g &S o •S 13 E 4) t u <" ^ o 2 8 2 e^™ UBS" Ssi's 376 DIAGNOSIS OF EAELY PULMONARY TUBERCULOSIS in another or even at ten or eleven o'clock at night. My plan, where there is doubt, is to have a two-hourly chart made for a few days until I can see at what time the maximum temperature ap- pears. I then choose this as one of the hours of the day when temperatures are to be recorded. I wish also to emphasize the importance of the early morning temperature. If one will observe the temperature in the morn- ing when the patient awakens before the activities of the day begin he will have a very important starting point for observa- tion. The temperature at this time of day, depending on the time that it is taken, should be from 97.2° to 98° F. If we find the temperature 98.6° at this time, it is probable that active dis- ease is present, but may be evidence of an early rise of normal temperature for the individual patient as shown in the Figs. 76 and 77. The normal daily variation in temperature is about one and a half degrees. Unless the patient's temperature is at this low point in the morning, he is suffering from a constant rise. It is not sufficient to take the maximum temperature for the full study of the fever curve, but the early morning tem- perature must be equally considered for the diurnal variation is of value in determining the stability of heat regulation. I usually construct my temperature curve from that taken on awakening in the morning, twelve, four and eight o 'clock unless the maximum should fall on some other hour. Fig. 113, Vol. II, shows a normal temperature curve for the day, while Figs. 76 and 77 show the im- portance of the early morning record. There are many sources of error in taking temperature. In the first place, the thermometer should be held in the mouth suf- ficiently long to fully register. I am in the habit of requiring patients to hold the thermometer a minimum of five minutes, no matter whether it be a one minute, two minute, or three minute thermometer. If the weather is cold and the cheeks are chilled, the temperature will not record in this time. The thermometer must sometimes be held ten or fifteen minutes to secure a full reading. It takes ten to twelve minutes to warm the mouth if one has been riding in the cold or if one has been talking in the cold air. A single observation made at the time of the visit of TEMPERATURE IN DIAGNOSIS 377 ■3* .§» o 5 1).-; bo a 5 .„ c ° .2 O-Q C > 2 P.O rt * c s e * I*" > 378 DIAGNOSIS OF EARLY PULMONARY TUBERCULOSIS the patient to the physician's office is of no value in determining the presence or absence of rise in temperature. The patient should be instructed to hold his mouth closed dur- ing the entire time that the thermometer is registering. Mouth- breathers have great difficulty in registering their temperatures. In fact, mouth temperature in a mouth-breather has little value. The rectal temperature should be relied upon under these cir- cumstances. There are certain peculiar characteristics of the temperature curve that should be considered. First: Patients suffering from active tuberculosis do not neces- sarily have symptoms of toxemia with the maximum temperature above normal every day over a prolonged period of time. This toxemia is usually inconstant and shows waves of increase and decrease. The patient may have a rise of temperature above normal for a period of a week or more, succeeded by a like period of freedom from rise. It can be seen that if the temperature was taken during the period of acute exacerbation the patient would be said to have an elevation of temperature. However, if it were taken during the time when the acuteness of the tox- emia had passed, he would be said to have no rise of temper- ature; consequently it is impossible to .give a definite opinion of the temperature of the patient in whom early tuberculosis is suspected unless the chart be taken for a period of two or three weeks. This point is well illustrated by the chart in Fig. 78. The only time that this patient showed a rise in temperature was when he was suffering from pleurisy, the lesion being a sub- pleural one. (See page 377.) Another important variation to be noted is the premenstrual rise. This elevation of temperature varies greatly. In some in- stances it will be extremely regular, the temperature running from 98.6° to 99° in the afternoon for the two weeks prior to menstruation and from 98° to normal for the two weeks follow- ing menstruation. In others the elevation of temperature will appear only a week or a few days before the menstrual time. In still others it will appear during the period and continue for a short time; but this is the exception. The cause of this most common rise in the temperature curve prior to menstruation TEMPERATURE IN DIAGNOSIS 379 1 38C DIAGNOSIS OF EAELY PULMONARY TUBERCULOSIS where the daily maximum amounts to little more than one- half of one degree Fahrenheit, we must look for in something which interferes with the normal elimination of heat. This we have in the stimulation of the vasoconstrictors caused by the ovarian secretion produced during this time, as discussed more fully on page 195. More marked rises in temperature which occur immediately preceding or during the period, and which continue through menstruation, are probably associated with inflammatory con- ditions in the genital organs. This premenstrual curve, as far as I have been able to determine, appears the same in normal women as it does in the tuberculous, although I have had only a few persons who were able to keep a chart for me sufficiently long to be of value; yet this is what should be expected on phys- iological grounds. If there should be a rise in the temperature curve during this premenstrual time, I would not give it, of itself, any diagnostic worth, but would wait and take the temperature again follow- ing the cessation of menstruation. The premenstrual rise is shown in Fig. 76, in which it will be seen that the temperature as a whole was about one-half degree higher from the 4th to the 17th of the month. It showed a slight decline on the 17th, the 18th being the first day of menstruation. (See page 374.) Patients can readily be taught to take their own temperature and pulse and this is far better than to rely on the irregular observations made by the physician in his office. From one-half to one degree should be allowed for nervousness on the first visit to the physician. A very annoying temperature curve is often shown by those of nervous temperament. It is characterized by irregularity, being up one day and down the next. While this character of curve is often met with in the tuberculous patient, the irregu- larities are not primarily due to the tuberculous process. Fig. 79 illustrates this rise of temperature. Such rises of temperature may continue in nervous individuals for months after the dis- ease is arrested. It is often difficult to convince them that these rises are not serious and that they are not caused by active proc- esses. The probable explanation is that, through the action on ACCELERATION OF PULSE 381 the nervous system, stimulation of the vasoconstrictors is pro- duced which interferes with the elimination of heat. There is a tendency on the part of some observers to go too far and to try and account for nearly all persistent rises of tem- perature as being of tuberculous origin ; but when other suspicious symptoms are absent, we must remember that infections of the tonsils, teeth, appendix, and genital organs, particularly the prostate and fallopian tubes, or infection of any other part of the body, can cause an elevation of the temperature curve. Fig. 80, A and B, shows a curve in a patient who was suffering from chronic inactive tuberculosis and who developed a tonsillitis. A local infection remained in the tonsil, causing the temperature curve here shown. (See pages 382 and 383.) Acceleration of the Pulse. — The acceleration of the pulse noted during early active tuberculosis is a symptom which re- sults chiefly from the disturbance - of the inspiratory act and from the effect of toxins upon the sympathetic nervous system. The degree of acceleration of the pulse in early tuberculosis varies considerably according to the individual. In young per- sons it is apt to be greatest, but varies considerably according to whether the patient is vagotonic or sympathetotonie, accord- ing to the ideas of Eppinger and Hess. After the symptoms of activity have disappeared, the pulse returns to a normal rate, or the degree of acceleration is lessened. The peculiar charac- teristics of the pulse in early tuberculosis will be discussed more fully later on in this chapter in discussing the effect of reflex action; but, it should be said at this point that the degree of rapidity of the pulse is the resultant largely of sympathetic stimulation caused by toxemia and increased output of adrenin on the one hand, and reflex stimulation of the vagus produced by the inflammation in the lung, on the other hand. During periods of toxemia, sympathetic stimulation usually predominates and the pulse becomes accelerated. After the activity has passed by, either vagus or sympathetic stimulation may be most marked according to the individual. If one should expect to follow the ac- cepted teaching that acceleration of the pulse is the particular char- acteristic of active tuberculosis, he could go wrong in the majority of instances, because acceleration is not regularly present unless the patient is depressed or overexerting. 382 DIAGNOSIS OF EARLY PULMONARY TUBERCULOSIS o s ^1 rt o <1. D. C s c o "5 O .3 *+* n .-£$ br £ c c 3 .G 3 ji n t) 3 | o „M Sua ^= ^ II tt> U o 1) w sj u a 5=1 = ~ SHSj-gs! 60 3 p 3 x ° S g.g •55 ^ o rt S 2 v ™ S 3 a g g d fJ a m S •£•".2 S T1 2 ir O o ■" — OJ g tn r- 4J - •" a d S - ** M — .S bo ^.5-2.2 « • n) X > "'? ot " 60- v te S — o > C 01 bo K A '53 ft tJ .Q u J3 _> X ■*-* o ft 53 > ta ,rH . >5 — C rt C 's- T<; 11 o (J c« C (LI .£3 O n) > o 13 -S 3 I * " s JJ 1.3 « 00 X B 5 bo ^■^2 .J4 (S £ v fi "3 3 xn ° ^c i a 1 nl '5, o bp £ rt rt. s o ~ o l-f C ■J J3 o CHANGES IN CONTOUR AND MOVEMENT 469 If a flattened appearance is noted over one or the other apices, it should be carefully examined to see if it is a real flattening of the chest wall or only a wasting of the soft tissues, which often gives the same appearance; or both. Either condition is sug- gestive of chronic inflammation in the pulmonary tissue under- lying. Should the flattening be at the base, pleurisy with ad- hesions is suggested. Wherever the flattening is, it is usually accompanied by a limited motion of the part of the chest wall overlying it. Enlargement and bulging of portions of the chest wall are also very commonly found. They are usually due to compensatory emphysema and indicate that a destructive process has taken place in other portions of the same lung or in the other lung, which has caused the underlying pulmonary tissue to enlarge. The respiratory movements on the side of the emphysema are usually greater than normal, while those on the other side, are less than normal. Bulging may also be due to fluid or air in the pleura. A correct differential diagnosis can often be made by careful analysis of the data on inspection. A limitation of motion on one side nearly always means acute or chronic disease within the lung or pleura on that side, while increased motion means, as a rule, compensatory enlargement be- cause of an extensive destructive process on the other side. The following cases illustrate the relation of careful inspection to diagnosis in advanced tuberculosis : Case I. Mr. 0. Extensive fibroid tuberculosis in right lung, with cavity at apex; compensatory emphysema at right base; thickened pleura at right base; chronic fibrosis upper portion left lung; compensatory emphysema through- out left lung; heart displaced slightly to the right; right diaphragm dis- placed upward; left diaphragm displaced downward. Inspection of Muscles and Subcutaneous Tissue. — The chest is long and flattened superiorly. The neck muscles and subcutaneous tissue over them, as well as those below the clavicle on both sides, appear degenerated, this being more marked on the right than on the left. Both sterno- cleidomastoidei stand out more prominently than normal because of the degen- eration of the subcutaneous tissue surrounding them. From the general atrophy of the muscles and subcutaneous tissue over the entire portion of the right lung, I would infer that there is either 470 PHYSICAL EXAMINATION IN PULMONARY TUBERCULOSIS a thickened pleura or some inflammatory condition throughout the un- derlying lung, or both. The atrophy of the muscles and subcutaneous tissue on the left is confined to that portion of the chest above the second rib, indicating a less extensive lesion. Inspecting the chest posteriorly we first notice that it is long, also fairly broad. We next notice that the muscles over the right shoulder, with the subcutaneous tissue over them, are markedly degenerated, the right shoulder being considerably lower than the left. The occipital por- tion of the trapezius is more degenerated than that on the left side. The degeneration of the muscles and subcutaneous tissue runs almost to the base on the right. There is also a degeneration of the muscles and subcutaneous tissue at the upper left, though of lesser degree and lesser extent than that on the right. Motility. — Different portions of the chest anteriorly show unequal mo- tion. We can divide the chest into two portions, with a line running from the left acromial process to the sixth rib in the anterior axillary line on the right side. Above this line we have decreased motion and be- low increased motion. The increased motion is greatest on the left. From this we can infer from inspection that there has been a destructive process above this line, more severe on the right and less extensive in the upper left. We can further infer that compensation has occurred and that the lower part of the left lung is the seat of a marked and widespread em- physema, and the lower part of the right is the seat of a less extensive emphysema. Posteriorly, the chest is not so distinctly divided as to motion, although a line drawn from the outer third of the shoulder on the left to the lower angle of the scapula on the right will divide the posterior portion of the chest into two areas of greater and lesser motion. The motion, being so much less at the upper right than at the upper left, we would infer that there has been a much greater destructive process in the upper portion of the right lung than in any other portion of the chest. Altered motion in the upper part of the left as compared with the lower portion of the left, would also indicate that there has been some destructive process in the upper portion of the left lung. Greatly increased motion through- out the left, and particularly at the base, would indicate the presence of emphysema. The increased motion at the right base as compared with the upper portion of the same lung, would also indicate that there is some emphysema at this point. Case n. Mr. P. Chronic fibro-uleerative tuberculosis of left lung, with large secreting cavities in upper and lower lobe; lung very much contracted; entire mediastinum drawn to left; scattered healed tubercles through- out right lung; marked compensatory emphysema; trachea to left of .me- dian line; heart, left border anterior axillary line, right border to left of median line; left diaphragm markedly displaced upward; right dia- phragm markedly displaced downward. At present time condition quies- cent. CASE ILLUSTRATING VALUE OF INSPECTION 471 Inspection of Muscles and Subcutaneous Tissue. — Anteriorly there is a flattening over both upper lobes. The left side somewhat more depressed than the right. The motion throughout the left side is diminished — markedly so at the base. The left sternocleidomastoideus is markedly degenerated, but stands out more prominently than normal because of the degeneration of the subcutaneous tissue over it and the retraction of tissues under it. The right sternocleidomastoideus with the subcutaneous tissue over it is degenerated. The supraclavicular notch is deepened on both sides. The left pectoralis and the subcutaneous tissue over it is markedly degenerated to the fourth rib. The trachea can be seen dis- placed to the left. The heart pulsation is increased in an area extend- ing from one and one-half inches to the left of the left nipple to an inch to the right of the nipple. Posteriorly, the left shoulder is much lower than the right and the left side of the chest is smaller than the right throughout. The right is somewhat bulging. The angle formed by the junction of the middle with the occipital portion of the trapezius is one inch lower on the left than on the right, while the trapezius, levator anguli scapulas, rhomboidei, and the subcutaneous tissue over them, extending to the base, is markedly degenerated. On the right the trapezius and levator anguli scapulas are also slightly degenerated. Motility. — The motion on the left is diminished throughout and on the right side is greater than normal. From inspection alone we cannot tell whether or not activity is pres- ent; but, from the fact that the left side of the chest is markedly smaller than the right, together with the lessened motion and the atrophy of the muscles and subcutaneous tissue over this side; and the fact that the trachea runs toward the left above the jugulum; and that the maximum impulse of the heart extends to the left axilla, we infer that there has been an extensive chronic destructive process involving the left lung. From the fact that the muscles over the apex and the subcutaneous tis- sue covering them on the right side are degenerated, we would infer that there has also been a chronic inflammation affecting the underlying lung on this side. From the bulging of the right side and the increased motion throughout we would infer that there is a compensatory emphysema in- volving the entire right lung. The position and motion of the acromion processes (Korani) ; drooping of the shoulders; shape [scaphoid scapulae (Graves)], position, and motion of the scapulae, are all of diagnostic import. One should train his powers of observation. It is only necessary to look at chests carefully and analytically in order to form a fairly correct idea of the lung and pleural pathology within. We do not expect to find the classical phthisical habitus except in a small proportion of cases. We expect to find chests of the same size and shape as we find regularly among well people, ex- cept as they are deformed as a result of the tuberculosis. 472 PHYSICAL EXAMINATION IN PULMONARY TUBERCULOSIS PALPATION. When the data which may be derived from palpation is added to that which may be derived from carefully inspecting a chest, sufficient information is at hand, in the majority of cases, pro- viding it is carefully analyzed, to determine: 1. Whether or not there is a pathological process in the lungs. 2. Its extent. 3. Whether it is active, chronic, or healed. 4. Whether sufficient destruction has occurred to produce: (a) Compensatory emphysema. (b) Compensatory shifting of the mediastinum. (c) Compensatory shifting of the diaphragm. 5. Whether or not pleurisy is or has been present and if so whether it has resulted in marked adhesions. 6. The nature of the process, the density of the infiltration, and whether or not destruction of tissue with cavity formation has occurred. Inspection and palpation have not received the attention that they deserve. They require no greater skill on the part of the examiner than percussion and auscultation, but they require to be practiced; and, the data obtained requires thoughtful analysis if they are to be of great value to clinical medicine. Palpation as usually practiced is of limited usefulness. It is confined to determining the vocal fremitus, to demonstrating pleural friction or the fremitus produced by rales, noting en- larged glands, locating the apex beat, determining expansion and eliciting pain. Determining these is the least important func- tion of palpation. Valuable information is obtained by know- ing the location of the heart beat and the altered conducting power of various pulmonary areas, together with the expansile activity of various portions of the chest. The greatest value, however, comes through: 1. Studying the conditions of the skin, subcutaneous tissue and muscles with reference to the reflex motor and trophic changes which they undergo in the presence of acute and chronic diseases within the thorax. 2. Carefully noting the departures from the normal in the PALPATION OF SOFT STRUCTURES 473 movements of the various parts of the thorax in confirmation of the alterations noted on inspection. 3. Noting the differences in density (resistance) over the various portions of the lung suggestive of infiltration, cavity, fibrosis, emphysema, thickened pleura and pleural effusions ; and noting the shifting of the mediastinum and borders of the lungs. Palpation of Muscles and Subcutaneous Tissue. — The impor- tance of palpating the soft parts covering the bony thorax for degenerations confined to limited areas in advanced tuberculosis, cannot be emphasized too strongly, for each organ within the body is so connected through its sympathetic nerves with the spinal nerves that any inflammation in that organ reflects some- where on the surface in sensory, motor and trophic disturbances. The point where these reflex manifestations shall show them- selves is determined by the nerve filaments which take their origin from the segments of the cord which receive the impulses from the nerves coming from the organ in question. In the case of the lung, the cervical segments particularly the third and fourth, receive the impulses and these give out sensory and trophic im- pulses to the skin and subcutaneous tissue of portions of the neck, arms and chest, and motor and trophic impulses particularly to the muscles of respiration, including the diaphragm. As previously mentioned, this circumscribed (regional) atrophy is not the same as the general wasting. It occurs whenever and wherever an inflammation has existed long enough to become chronic, whether it was sufficiently extensive to interfere with the general health of the individual or not. "We detect localized areas of atrophy of the skin and subcutaneous tissue over the supraclavicular notch, or over the first interspace, or above the spine of the scapula, also the wasting of the sternocleido- mastoideus, upper fibers of the pectoralis and trapezius when the underlying apex is the seat of a small, chronic or healed tuber- culous lesion. We see this extend and become widespread, in- volving the tissue to the third and fourth rib and down to the base of the scapula, or lower, as the tuberculous process extends lower and lower. If the pathological process in the lung re- mains confined to one lung, the atrophy of the skin, subcutaneous tissues, and muscles will be confined to the same side, until such 474 PHYSICAL EXAMINATION IN PULMONARY TUBERCULOSIS time as the general wasting is sufficient to manifest itself, then all the tissues of the body partake of it, and the regional wasting is overshadowed by the general process and is hard to determine. Prior to this time, however, any atrophy of the soft parts should be carefully scrutinized to see if it is limited in its extent, and regional in character. The regional wasting can be determined by inspection, but it is confirmed, and at times, better determined by palpation. When the palpating fingers press upon the soft tissues which are atrophied, several different conditions may be noted. The skin may feel thin and loose. If taken between the fingers it may be noted that the skin over the first interspace is thinner than that over the first on the other side or that over the second in- terspace of the same side. The subcutaneous tissue may appear to be wasted. The usual cushion is not there. The fibers of the underlying muscles or the underlying bones are felt more distinctly than in areas close at hand or those on the other side. The skin is not bound firmly to the underlying tissues but can be picked up and lifted from them with ease. The muscles feel wasted. The bundles are looser and more free- ly movable in the tissues surrounding them than they should be — looser than those adjacent. The bundles are made out more easily and they separate more readily than they do in normal muscles. The substance of the muscle, as a whole, is reduced in amount. This shows exceptionally well in the sternocleido- mastoideus where it can be taken between the thumb and finger and its size and texture compared with its mate. The degree of wasting present can also be detected by pressing the soft tissues gently against the chest wall and noting the comparative lack of tissue where the regional wasting has taken place. A normal muscle is more or less compact, often rotund, and feels like one firm elastic mass, while a wasted muscle has lost its tone as well as compactness and rotundity. Finally the feeling of the tissues which are atrophied is dis- tinctive. The normal elasticity is gone and the tissues give a doughy sensation to the finger. "While spasm of the muscles may often be detected in advanced MOTILITY OF CHEST WALL 475 eases when the disease in the lung is a renewed activity in an old focus, yet this is attended by difficulties owing to the in- creased tone (spasm) being difficult to recognize on account of the atrophied muscle. Increased tone (spasm.) is important, how- ever, in determining whether the disease has extended to the other side and in determining whether it has extended to other areas in the lung. Degeneration of the muscles covering the apex, and the skin and subcutaneous tissue over them, is suspicious of a tuberculous lesion, chronic in nature, affecting the underlying apex. If the lower fibers of the pectoralis and the overlying skin and subcu- taneous tissues are also involved, this is suspicious of a chronic tuberculosis involving the entire upper lobe. If the rhom- boidei and the skin and subcutaneous tissue over them are de- generated, it indicates that the apex of the lower lobe is the seat of a chronic inflammation, usually tuberculosis. Muscles also degenerate and lengthen as a result of use. The drop of the right shoulder in part is due to this. It is, at times, difficult to tell whether a right-sided degeneration of the apical muscles is due to occupational influences or to reflex trophic dis- turbances. Conditions found in these muscles are at times difficult to interpret. Two facts have helped me: first, the sternocleido- mastoideus is not subject to many occupational influences ; so a. one-sided spasm or degeneration of the apical group of muscles, including this one, points to a reflex trophic cause for the degen- eration: second, the skin and subcutaneous tissue does not atrophy as a result of occupational influences, but does so as a result of reflex trophic irritation. Again, if the atrophy is due to pathological changes in the lung, this will be detected on deep palpation, percussion, and auscultation. Motility of Chest Wall. — Either a limitation or exaggeration of movement of any portion of the chest is at times more easily de- tected by palpation than by inspection. Any such departure from the normal movements of the chest is suspicious of patho- logical changes either in the lung or pleura, or both. In advanced tuberculosis lessened motion of the diaphragm or chest wall may be due to acute or chronic inflammation of the pleura, or to an active infiltration or an old chronic fibrosis in 476 PHYSICAL EXAMINATION IN PULMONARY TUBERCULOSIS the lung. Increased motion of the diaphragm, or chest wall, is a compensatory phenomenon and may be found on the side opposite to an acute pleurisy or on the side of a compensatory emphysema. A limitation of motion of the upper portion of the chest may be due to an active inflammation at that apex, the lessened mo- tion resulting from the combined action of the thickening of the pleura and the reflex spasm of the respiratory muscles fixing the thorax, and the lack of elasticity in the tissues, resulting from the infiltrating inflammation in the lung; or fibroid changes in the pulmonary tissue. Departures from the normal respiratory movements can best be interpreted when considered in conjunction with the trophic and motor changes in the soft parts. Determination of Different Degrees of Density by Palpation. — "The principle involved in palpation and percussion is the same when the interpretation of the latter is based on the sensation conveyed to the finger rather than to the sound emitted by the blow. Palpation, no matter how delicately carried out, sets up vibrations and disturbs the equilibrium of the tissues on which it is practiced. The touch starts waves which penetrate the tis- sues and, according to the manner in which these waves are in- terfered with, do the sensations conveyed to the finger differ. So, whether we generate the vibrations by touch or by a gentle stroke the effect is the same, a varied penetration and varied in- terference with the vibrations and a varied perception through the palpating finger, which is interpreted as meaning different degrees of density of the underlying tissues." 1 By carefully palpating, the examiner will learn that different degrees of density are transmitted to the finger through the sense of touch, the same as they are through sound or percus- sion resistance. Conditions which are recognized by differences in pitch and quality of the note elicited on stroke, and by dif- ferent degrees of resistance to the finger used as a pleximeter on percussion, also convey different impressions through the sense of touch by which we are able to recognize normal and abnormal conditions within the body. Light touch palpation affords the jPottenger: Muscle Spasm and Degeneration and Light Touch Palpation, C. V. Mosby Co., St. Louis, 1912. PERCUSSION 477 greatest acuteness in interpretation because the sense of feeling in the finger pulps is utilized to greatest advantage. Various degrees of palpation should be utilized, however, for different conditions, as the observer will soon learn for himself. The normal lung, the borders of the lung whether within nor- mal limits or shifted, infiltrations, fibroid areas, cavity, emphy- sema, pleural effusions, pneumothorax, thickened pleura, media- stinal tumors and enlarged peribronchial glands ; in fact all con- ditions which can be determined by percussion, can be deter- mined by palpation. The peculiar characteristics of each of these as determined by the palpating finger I shall discuss later in con- junction with the other methods of examination. PERCUSSION. The principles and technic of percussion are the same as in early tuberculosis as discussed on page 417, although a greater variety of changes will be noted because of the more varied and more extensive character of the pathological changes found. In such a complex condition as advanced tuberculosis, where all grades of infiltration, various degrees of excavation and com- pensation, such conditions as pleural effusion, pneumothorax, thickened pleura, and compensatory emphysema are found, it can readily be seen that we must draw conclusions from percus- sion only after careful consideration. Not only the changes in percussion note, but the different degrees of resistance to the finger must be carefully noted. The condition of the muscles and subcutaneous tissue must also be carefully observed, and allowance must be made for increased tone as noted when the muscle is overdeveloped or thrown into spasm reflexly, and decreased tone, when it and the subcu- taneous tissue is degenerated as a result of occupational change or reflex atrophy. Any increase in muscle substance or any increase in tone in individual muscles is followed by an impair- ment of the note and higher pitch, also by an increased resistance to the finger. Any wasting on the other hand, no matter from what cause, is followed by a corresponding reduction in dull- ness and lowering of pitch, as well as a reduction of resistance 478 PHYSICAL EXAMINATION IN PULMONARY TUBERCULOSIS to the finger. For a more complete discussion of factors which alter percussion findings see Chapter XV. AUSCULTATION. Auscultation in advanced tuberculosis shows many departures from the normal in the respiratory sounds. These departures consist of a disturbance in the rhythm, pitch and quality of the respiratory murmur; a number of adventitious sounds; and al- terations in the manner in which the voice is transmitted. It is impossible to describe in detail all the changes which oc- cur in the respiratory murmur in advanced tuberculosis for they vary under different circumstances. While there are certain characteristic sounds which belong to infiltration, others to soften- ing and cavity formation, and still others to fibrosis; yet these processes are found in such varied combinations and differ so in their extent; and the sounds are so modified by the state of the remaining portions of the lung, the condition of the pleura and the state of the muscles and subcutaneous tissue through which they are heard, that we must be prepared to find all kinds of combinations of sounds in advanced tuberculosis. Respiratory Rhythm. — The normal relationship of inspiration to expiration is disturbed in such a manner that as infiltration increases expiration gradually lengthens until it finally becomes equal to or longer than inspiration. The change in rhythm is usually accounted for in tuberculosis by the consolidation caus- ing the bronchi to be more rigid and the tissues less elastic, as a result of which the air is forced out of the tissue more slowly and the sound emitted transmitted more readily. So it can be understood that all degrees of prolonged expiration exist in tis- sues the character of which varies from slight infiltration to marked fibrosis or cavities and dilated bronchi surrounded by dense fibrous tissue. I do not doubt that the atrophy of the soft tissues external to the pleura also has its influence by removing a compressing influence on the thorax, thus prolonging the expiratory phase. When compensatory emphysema occurs, then the prolonged expiration is due to an inability of the pulmonary tissue to contract and expel the air, but the quality of the note differs wholly because QUALITY OP RESPIRATORY NOTE 479 it lacks the conditions for ready transmission. While the expira- tory note of consolidation and scar tissue is more intense and higher in pitch than normal, that of compensatory emphysema is lower pitched and weaker than normal. Quality of Note. — The quality of the respiratory note also varies greatly. As the pathological changes in the lung extend, the soft breezy normal inspiration gives way to a rough, harsh, or combined rough and harsh, inspiration with pitch higher than normal. The same is true of expiration. Expiration, as a rule, is equal to or of higher pitch than inspiration when consolida- tion is present; and particularly in the presence of dense fibrous tissue. When excavation has occurred, however, there is a tendency for the pitch of the expiratory note to be lower than that of inspiration, unless the cavity is small and surrounded by large amounts of dense fibrous tissue. This is an important sign of cavity. The roughness w T hich so often characterizes the respiratory note in advanced tuberculosis probably has many factors which enter into its composition. It has been suggested that roughness in early tuberculosis may be caused by an unequal entrance of air into the tissues. The condition which would produce roughness because of such unequal entrance, is found to an exaggerated degree in advanced tuberculosis, because of the varied patho- logical processes which are present. In advanced tuberculosis there is often found coexisting in the same lung, or even the same lobe, varying degrees of infiltration accompanied by vary- ing degrees of exudation, areas of necrosis, excavation and fibrosis. The effect of the muscles in producing the roughened char- acter of the note must also be considered. The peculiar rough, rumbling respiratory note over compensatory emphysema un- doubtedly has a large muscular element in its production. Thick- enings of the pleura which are stretched during respiration also add a roughened character. Changes in the respiratory note in advanced tuberculosis con- sist in replacing the normal vesicular murmur by one which, at first, is somewhat bronchial in character, but which, later, after 480 PHYSICAL EXAMINATION IN PULMONARY TUBERCULOSIS pathological changes become sufficiently extensive, becomes en- tirely so. This, in turn, becomes amphoric when excavation oc- curs. Rales. — Rales or adventitious sounds accompany the respira- tory murmur in nearly all cases of widespread pulmonary tuber- culosis. These rales vary in nature as they differ in the manner of their production. Rales are divided into moist and dry. Some writers claim that all intrapulmonary rales originate with mois- ture. At times stretching of scar tissue, pleural adhesions and muscles will produce sounds that cannot be differentiated from the intrapulmonary sounds. The methods of differentiating intra- pulmonary and extrapulmonary rales is uncertain. Rales are affected by the depth of respiration, cough, position of the patient, whether the patient has coughed and expectorated immediately prior to examination or not, the time of the day, fever, conditions of weather, and many other factors, as well as the pathological process which produces them. By making frequent examinations of a tuberculous lung over a prolonged period of time it will be noted that the rales are characterized by constancy. When rales appear in an area they go through certain evolutionary changes but do not leave the part wholly until healing or wholesale destruction with cavity formation has taken place and not always then. They might be temporarily put in abeyance by a pleural exudate or pneumo- thorax, but they do not disappear until the cause disappears. Many rales remain permanently, even after an apparent healing has occurred. Rales, to a certain extent, indicate the nature of the pathological process underlying. Probably, if we were more expert in our interpretation, they would be even more accurate. The first rales which make their appearance are those which accompany infiltration, the so-called dry crackle or crepitant rales. They are found in the areas which have been recently affected. At this time the process is accompanied by very little exudation into the tissues surrounding the tubercles. The rales are confined to the finer air passages, largely to the air cells. The result is that the rales are fine and dry in character and are elicited best by increased inspiratory effort or by this preceded by a cough. RALES . 481 In auscultating over early active infiltrations, these rales are often heard in small showers after coughing. In more advanced lesions in which the bacilli are multiplying, tubercles are soften- ing and toxins are diffusing into adjacent tissues, a greater de- gree of inflammation exists and this is accompanied by increased exudation. This process is accompanied by increased moisture in the air passages which finds its way into the bronchi of differ- ent sizes and in this way produces moist rales, both medium and large in character. In localized areas of necrosis with cavity formation medium or large rales may persist for a long time. The location of con- glomerate caseating tubercle is often marked by the persistence of medium and large rales heard over a given area for a con- siderable time. If extensive excavation takes place the rales may disappear wholly, or decrease in number coincident with the sloughing of the tissue. Where one has been examining patients repeatedly, this cavity formation may be suspected by the ab- sence of medium and large rales which have persisted for a long time. On the other hand, there are times when, coincident with such pathological changes, the rales become coarser and bub- bling or gurgling in character, owing to the air forcing its way through the mucus or pus which is present in the cavity. When healing is taking place, the multiplication of bacilli in the tubercles is lessening, and the amount of toxins diffusing into the adjacent tissue is decreasing, consequently the exudative in- flammation which accompanies active inflammation decreases and the amount of moisture which shows as moist rales, lessens and the tissues appear to the examiner to be of a dryer character. This statement must not be considered as conflicting with the fact, which is often evident in the fibro-ulcerative type of tuber- culosis, that the amount of sputum does not necessarily lessen in the proportion to the lessening of rales. The explanation is that the sputum is coming from ulcerative surfaces within cavities instead of from the bronchial mucous membrane. Not only do we have the three types of distinctly moist rales just described, but there are squeaks, wheezes, and ronchi of great variety. Often a persistent squeak at some point in the pulmonary tissue indicates that softening and ulceration is tak- 482 PHYSICAL EXAMINATION IN PULMONARY TUBERCULOSIS ing place. Wheezes and ronchi are at times present in such num- bers that the picture resembles asthma. Adventitious Sounds Resembling" Intrapulmonary Rales. — The examiner is often much confused in knowing how to interpret the adventitious sounds which are heard upon auscultation. I have just described many different types of rales that have their origin within the lung. These rales would seem to be more or less distinctive of certain conditions which produce them. There are, however, many sounds heard on auscultation, which cannot be readily differentiated from the intrapulmonary rales just mentioned. Pleural crepitations are, at times, very difficult to differentiate from intrapulmonary rales. The muscles also, now and then, give us sounds which cause difficulty in diagnosis. Sometimes these are fine crepitations, sometimes they simulate medium, and, at other times even coarse rales; or, they may even take the form of creaks and squeaks. We find many of these near the apex where the pleura becomes thickened, and the adjacent musculature and tissue also partake in the inflammatory process, as has been described by Coplin (see Volume II, Chapter XXV). These rales may be found in any part of the lung where a thick- ened pleura and chronically inflamed muscles exist. Swallowing will often produce sounds which simulate rales, when one is listening over the apices. After the patient has been observed for a long time, the true nature of these rales can usually be made out by the fact of their persistence and the knowledge of the changes which have occurred in the underlying pulmonary tissue. Where widespread pleural adhesions are present we may often infer that the rales are not intrapulmonary because of the fact that the amount of moisture which would be represented by such widely distributed pulmonary rales, is not in keeping with the amount of sputum present. Extensive Infiltration in One Lung. — In discussing the more common conditions which are met in the lung in advanced pul- monary tuberculosis I shall first consider extensive infiltration. Inspection. — What can be determined by inspection will de- pend, as previously mentioned, on whether the infiltration in the lung is recent or of long-standing, and upon whether it is a new EXTENSIVE INFILTRATION 483 infiltration in tissue which has not previously been infected, or a renewed activity in an old lesion. No matter whether the infiltration is a new or old one, if it is active, it causes a limitation of the respiratory movement of the chest wall. All active inflammations of the pulmonary par- enchyma cause reflex motor disturbance in the muscles of respira- tion which results in limited motion. The diaphragm, being the chief muscle of respiration, and being affected by this reflex, acts in such a manner as to greatly alter the respiratory movements. Interference with the elasticity of the pulmonary tissue, likewise causes diminished motion. Sometimes this limited motion is most pronounced at the apex. The apex is the usual site of the first acutely active tuberculous process in the lung, and when the disease is extensive, it is nearly always accompanied by pleural adhesions which also limit the respiratory motion. At other times, limited motion is most marked at the base; or, again, it may be equally distributed over the entire side. Limited motion is best detected, as a rule, during normal easy respiration. At times, however, it is best elicited on deep inspira- tion. Examination should be made during both shallow and forced respiration. The ehanges in the soft parts are often plainly visible, as de- scribed in discussing early tuberculosis in Chapter XV. In early tuberculosis, increased tone (spasm) of the muscles is of the greatest diagnostic significance. In advanced tuberculosis, as a rule, degeneration is most evident and of greater diagnostic im- portance than increased tone. This will vary, however, accord- ing to the activity of the pathological process; whether it in- volves tissues which have not been previously infected; or is an increased activity in an old focus. This latter is the condition usually met in advanced tuberculosis. Whenever a pathological process has existed over a pro- longed period of time and become chronic in character, the soft tissues over those portions of that lung, which are segmentally in reflex communication with the inflammatory areas in the lung, through the sympathetics, will show degeneration; consequently, degeneration of the soft tissues covering the chest, when regional 484 PHYSICAL EXAMINATION IN PULMONARY TUBERCULOSIS in character, becomes a very important sign of chronic inflam- mation in the underlying pulmonary tissue. If the inflammation is recent, aside from the degeneration, the muscles will show increased tone. This, at times can readily be detected on inspection, particularly in the sternocleidomastoid- eus, trapezius and levator anguli scapulae. If the process has been chronic and the muscles have accord- ingly degenerated, then it may be difficult or impossible to de- termine the increased tone on inspection; in fact, such an in- creased tone may be, now and then, especially in individuals with weak musculature, difficult to determine with certainty on pal- pation. Palpation. — Palpation shows increased tone of the muscles cov- ering the apex and upper portion of the lung if the disease is ac- tive and of recent extension. Degeneration of these same mus- cles and the subcutaneous tissues overlying them shows if the disease is of long duration. This is shown by the tissues pre- senting a soft, doughy, inelastic sensation to the palpating fin- gers, and by the fact that the cushion of subcutaneous tissue, likewise the mass of muscles is smaller in amount than normal. Increased tone may be noted in the degenerated muscles if the disease is chronic, but still active. At times, however, the de- generation will be so marked that the increased tone may not be detected. Even those with most practice may have difficulty in being sure of the increased tone under these circumstances. I would call attention to the fact, however, that the sternoeleido- mastoideus, trapezius, and levator anguli scapulae should be ex- amined most carefully under such conditions, for they will usu- ally reveal the true condition of the muscles in general. Palpation corroborates the lessened excursion of the side in- volved. As a rule, this important sign can be determined better by palpation than by inspection. The hands should be laid on lightly, however, for even slight pressure will restrict the move- ments. Through palpation we also determine the relative density of the lung tissue. If one is endeavoring to determine the areas of infiltration, it is better to palpate from areas of lesser density to those of greater density; consequently, in palpating lungs EXTENSIVE INFILTRATION 485 it is preferable to begin at the base and go upward, unless thickened pleura interferes. When the borders of the areas of infiltration are reached, an increased sense of resistance will be noted by the palpating finger. One must be on his guard in palpating the total resistance of the lung because there are other factors than the thickened pulmonary tissue which enter in and have a tendency to vitiate the findings, the same as they do in percussion. For example, in palpating in the axillary line, when one comes to the folds of the pectoral muscles an increased re- sistance is noted. This must not be considered as being neces- sarily due to the pathological changes in the lung. It must be considered in connection with the fact that the more tissue through which one palpates, the greater the resistance to the fingers. Another area which offers difficulties is the interscapu- lar region. An increased feeling of resistance is recognized by the palpating fingers when the lower border of the rhomboidei muscles is reached. This may be mistaken for infiltration. These same muscles give difficulty, and often mislead, in percussion the same as in palpation. Infiltrations in the lung are detected as readily by palpation as by percussion. If the existing infiltration is sufficiently extensive to call for compensatory changes in other portions of the lung, or in the opposite lung, a lessened total density may be noted over the emphysematous portions. This lessened total density is readily determined by comparing it with the increased deep resistance over the area of infiltration. Palpating over marked emphysema, however, often gives an increased resistance to the palpating finger, which may be mistaken for increased density in the un- derlying pulmonary tissue. This is due to the fact that marked emphysema causes an increased tension of the intercostal mus- cles which shows as increased resistance to the palpating finger. If, under such circumstances, however, one will palpate more deeply he will readily see that he is palpating over increased tension, but not over increased density. Permission.— Percussion will give results according to the state of the tissues percussed. The examiner must bear in mind, as mentioned in connection with percussion in early tuberculosis (page 420), that the percussion note and the degree of resist- 486 PHYSICAL EXAMINATION IN PULMONARY TUBERCULOSIS ance conveyed to the finger are influenced not only by the state of the underlying pulmonary tissue, but by the pleura, bony thorax, subcutaneous tissue and muscles. If the muscles are hypertrophied from use or increased in tone (spasm) because of the reflex irritation from the pulmonary inflammation, the percussion note will be higher and the resistance greater than normal. If they and the subcutaneous tissue are atrophied from reflex trophic changes or from disuse following hyper- trophy, then the note will be more resonant and the resistance less than normal. Thickened pleura will also cause higher pitch of the note and greater resistance to the finger. An infiltrated lung may show varying degrees of infiltration, each of which will give a different character to the percussion note, even though the coverings of the lung are always the same. These facts show that there can be no definite note or de- gree of resistance which will always mean a given degree of in- filtration in a lung. They show too that the percussion cannot be accurately interpreted without estimating the effect of the changes in the coverings of the lung, particularly the amount and the degree of increased tone or wasting of the muscles ; the amount and the degree of wasting of the subcutaneous tissue, and the amount of thickening of the pleura, when present. Failure to appreciate this is the cause of much error. Oftentimes an infiltration of greater density than really ex- ists will be indicated by the higher pitched note or greater re- sistance to the finger on percussion which results from the re- flex increased tone (spasm) of the muscles overlying the lung. While this condition is most often met in early tuberculosis, yet it is not infrequent in advanced cases when the disease has spread quickly. This is particularly apt to occur over the trapezius, levator anguli scapulas, and rhomboidei; and, at times, also over a well-developed pectoralis. On the other hand, an in- filtration of lesser degree than actually exists may be diagnosed when these same muscles and the subcutaneous tissue overly- ing them have wasted. This is most pronounced when the wast- ing is a reflex trophic change. At times, from reflex trophic changes, the soft parts on one side of the chest will be reduced fully one-third in mass as compared with the same muscles and EXTENSIVE INFILTRATION 487 subcutaneous tissue on the other side. The effect of this upon the data derived by percussion is considerable. The first extensive infiltration is very often in the lung op- posite to the one which was the seat of the original focus ; con- sequently the condition of the soft tissues is extremely impor- tant. Over the lung with the old lesion, there is wasting of varying extent and varying degrees, while over the area of the newer infiltration, unless it has existed for many months, there is increased tone (spasm) of the muscles. Bearing all these alterations in mind, and they are extremely important in advanced tuberculosis, we find the following condi- tions on percussion in extensive infiltration. If the tubercles are scattered over a considerable lung area, but not thickly set, they do not cause the amount of thickening of the tissue necessary to produce marked dullness; but inter- fere with the normal elasticity, jcause more or less relaxation of the pulmonary parenchyma and produce a note tympanitic in character. If the infiltration is more dense and particularly if the infec- tion is of such virulence as to produce much exudation in the tissues, then we have varying degrees of dullness according to the mass and virulence of the infiltration and the character of the exudation, leading up to the flatness of caseous pneumonia; and varying degrees of resistance to the finger reaching its maximum also in those cases which show the thickest studding of tubercles and the greatest amount of exudation. One condition which is extremely confusing is an infiltration which takes place in the second lung when it has been the seat of a high degree of compensatory emphysema because of a wide- spread destructive process in the other lung. Here the funda- mental findings on percussion are those of emphysema, — in- creased resonance and decreased resistance to the finger as com- pared with the normal. If the tension is extreme, however, and the chest bulging and the intercostal muscles stretched, the note may be somewhat tympanitic or dull and there may be a sense of increased resistance to the finger. This condition, while readily detected by the expert examiner, at times proves con- fusing to those of less experience. It can readily be seen that 488 PHYSICAL EXAMINATION IN PULMONARY TUBERCULOSIS infiltrations of slight or even moderate degree, when existing in such an emphysematous lung, might be overlooked on percus- sion, being overshadowed by the findings due to the underlying emphysema. Infiltrations underlying thickened pleura are extremely dif- ficult to make out on percussion because of the changes incident to the altered pleura. Auscultation. — Auscultation over infiltrated lung tissue shows a variety of sounds. Rales may or may not be present. Ex- tensive infiltrations may exist without rales. This fact is not sufficiently appreciated. Too much dependence in diagnosis is placed upon the absence or presence of rales, for it is a well established fact that there is a form of tuberculosis of low viru- lence which extends over wide areas, irritating the cells and causing new tissue formation, the entire process taking place without any marked exudation accompanying it, or without ul- ceration and loss of tissue. Auscultation over such areas shows a respiratory note often somewhat weakened; harsher than normal, and usually accompanied by a prolongation of the ex- piratory note. Eoughness is also a frequent characteristic if activity is present. If the process is more virulent, other pathological changes oc- cur. The bacilli multiply, necrosis occurs, toxins diffuse into adjacent structures, and exudation takes place. Such infil- trated areas show, on auscultation, aside from the characteristic harshness, roughness, prolongation of expiration, and a variety of accompanying rales. These may be fine, medium or coarse; dry or moist, according to the conditions surrounding their pro- duction. Fibrosis. — Fibrosis occurs in tuberculosis when the infecting bacilli are of a low grade of virulence. It is a result of irrita- tion whereby the tissues are stimulated to new growth. The cells multiply and the tissues thicken, increasing their density. Healing in tuberculosis results in the formation of fibrous tis- sue. "When ulceration has occurred, however, other conditions will also be present. The formation of fibrous tissue is, as a rule, a slow process, and the changes found on inspection, pal- pation and percussion are much the same as those of long-stand- FIBROSIS 489 ing infiltration. Consequently inspection and palpation show the degenerative changes in the muscles and subcutaneous tis- sue, often with diminished motion of the side. Increased density is also noted by palpating over the fibroid areas; and, if the process is extensive, a compensatory emphysema is usually pres- ent in other portions of the lungs not involved in the fibrosis which affords a decreased resistance to the palpating fingers. Percussion shows a higher pitched note with a degree of dull- ness and increased resistance to the finger which are com- mensurate with the amount of fibrosis present; and a note more resonant than normal with lessened resistance to the finger over the portions of lung tissue which are the seat of compensatory emphysema when this is present. Auscultation reveals varying degrees of harshness, often high pitched in character, with prolonged and often high pitched ex- piratory note. The latter is often of a blowing character and may simulate cavity. A point of differential value is that the blowing expiration in the presence of cavity is usually lower in pitch than the inspiratory note while that which accompanies fibrosis is higher. The note over fibrosis may also be accom- panied by adventitious sounds. Sometimes these arise in the pleura, sometimes in the fibrous tissue itself and at times in the muscles. Cavity. — Cavity results from caseation and rupture of tuber- cles. Cavities may be as small as pinheads or so large that they occupy an entire lobe or entire lung. At times no single large cavity but many small ones are present. Often several large communicating cavities exist. Cavities may have smooth dry walls or they may be ragged and secreting. The more chronic cavities, as a rule, have the smoothest walls. Cavities may be surrounded by scar tissue, or infiltrated tissue in any stage of pathological change to which tubercles are subject. The same cavity may at one time contain secretion, at another be empty. It can readily be seen that these various conditions cannot pro- duce the same physical signs. Often one sign will be present on one examination and be absent at another. This must be under- stood in order to avoid confusion. The history is of great value in determining whether or not cavities are to be suspected. From 490 PHYSICAL EXAMINATION IN PULMONARY TUBERCULOSIS history alone one can usually determine whether loss of tissue is to be suspected. Fever, accompanied by cough and free ex- pectoration, has nearly always been present at some previous time, even if not at the time of examination, if cavity is to be suspected. If the patient is expectorating more than 20 to 30 c.c. of sputum, unless an acute or chronic simple bronchitis is present, cavity is to be suspected. In chronic cases where heal- ing is occurring cavities may be found when the amount of sputum is decidedly small. Inspection. — There are times when the musculature and sub- cutaneous tissue on the front of the chest have wasted to a marked degree and superficial cavities may be suspected by the sinking in of the soft parts during inspiration. This, however, is not sufficiently reliable for diagnosis. Palpation. — Loss of tissue can often be readily detected on light touch palpation. In palpating over a tuberculous lung, infiltrated areas will be recognized by a degree of resistance to the finger, which is greater than normal. If a cavity, or several cavities are present which are alone or together sufficiently large to represent a considerable loss of lung tissue, they are detected by an area of decreased resistance noted by the palpating finger in the midst of the increased resistance which belongs to the surrounding infiltration. I have learned to rely on this sign — a resistance less than normal noted on palpation in an area sur- rounded by resistance greater than normal — as being the most constant evidence of loss of pulmonary tissue. This sign is pres- ent whether there is one large, or many small, or several com- municating cavities. It is also present at all times unless the cavity be filled with secretion. Percussion. — Percussion over cavities shows several changes from the note elicited over surrounding tissues. It may be im- paired, more resonant, tympanitic, or the pitch may be lower, or it may show the "cracked pot" or Wintrich phenomena. The character of the note depends much on the force of the percus- sion blow. There is no particular percussion sound or phenon- enon that is found with regularity over cavities. Increased resonance results from the loss of tissue and can usually be elicited, if the stroke is not too forceful and the cavity is suf- CAVITY 491 ficiently large. The note, however, is modified greatly by sur- rounding tissue, so the sound which particularly belongs to the cavity can best be elicited by a light stroke. To my mind the most characteristic note found over areas of excavation which are surrounded by infiltration, is a "dull tympany" elicited on a stroke of moderate force. "Cracked pot" may be heard over superficial cavities with smooth walls waen freely communicating with a bronchus. Most definite "cracked pot" sounds may be heard at one examination and be absent at another a few hours later, because of a closure of the cavity opening. Wintrich pointed out that the tympany over cavity assumes a higher pitch when the mouth is open. An absence of these signs must not be taken as having any bearing on the presence of cavity. Resonance over cavity is sometimes relatively greater because of marked wasting of soft tissues (muscles and subcutaneous tissues) which would otherwise add a dull character to the note. The lack of resistance to the finger is of greater importance than the character of the percussion note. The increased resist- ance noted over thn infiltrated area will be absent where excava- tion has occurred, as mentioned under palpation. This condition in the midst of dullness can mean but one thing — a lack of tis- sue underlying, and while this might be due to a dilated bronchus or a circumscribed pneumothorax as a rule it means cavity. Auscultation. — Auscultation over cavities may reveal un- doubted proof of their existence or questionable or negative in- formation. Where the examiner has been listening at frequent intervals over a considerable period of time over areas the seat of widespread infiltration and caseation, he will now and then find that the rales have suddenly disappeared and the sounds have become clearer. This does not mean that the tubercles have become less active and that collateral inflammation has disap- peared and that cicatrization is progressing; but it means that the tissue has sloughed out leaving a cavity behind. An acute cavity may be suspected at times on this finding alone. Chronic cavities may also be suspected by an absence of rales in the presence of large quantities of sputum. If the sputum comes from disseminated areas of infiltration and necrosis in the 492 PHYSICAL EXAMINATION IN PULMONARY TUBERCULOSIS pulmonary tissue, medium and large-sized rales will be heard in abundance over the entire area affected; but, if the tissues are free from rales, this shows that the sputum must come from elsewhere, a cavity or cavities, empyema with bronchial fistula being the only alternative. Not infrequently do we find patients suffering from chronic inactive tuberculosis who expectorate 50 to 100 c.c. of sputum daily, but who show few rales on exami- nation. On the contrary coarse bubbling rales, localized and per- sistent, often suggest cavity. These may be metallic in charac- ter, particularly if the cavity is large and possessed of smooth walls. If cavities are superficial and covered by thickened pleura, or if they are surrounded by scar tissue, aside from the rales which originate -within the cavity, many adventitious sounds are at times heard. These may simulate medium rales, but, as a rule, are dry in character and heard both on inspiration and expira- tion. The breath sounds heard over cavity may be changed very little, if any, from those over the surrounding tissue. Some- times the sounds are diminished, this particularly when some interference with the ingress of air exists. Blowing expiration is frequently found over cavities, but is not pathognomonic. This character of breathing is also found at times over scar tissue, particularly near the apex. I am in- fluenced very much in my decision as to whether the blowing is due to cavity or scar tissue by the relative pitch of the inspira- tory and expiratory sounds. If expiration is higher pitched than inspiration the blowing is most apt to be due to fibrosis; if it be lower pitched it suggests cavity. Amphoric breathing is occasionally found, but only in a small percentage of cases; and only at times in these. A peculiar dis- tinct echo on coughing is sometimes transmitted to the stetho- scope. While this is not regularly heard, it is characteristic of cavity. A study of whispered voice transmission helps to detect cavity. Such syllables as "one," "two," "three," "ha," "ha," or "whis- per-r-r-r" are more distinctly transmitted as syllables over cav- ity than over infiltration or fibrosis, and when considered in con- COMPENSATORY EMPHYSEMA 493 junction with other signs are of value in diagnosis. A cavity large enough to give signs must be about as large as a walnut. Several smaller ones in groups, however, may be detected. As a result of the compensatory changes within the thorax small cavities may be compressed and disappear; and large ones may be so compressed as to completely alter the signs and symptoms caused by them. An alteration or disappearance of signs after once being found must not be taken as indicating that the pre- vious findings were incorrect. Compensatory Emphysema. — Compensatory emphysema is a part of practically every advanced case of pulmonary tubercu- losis that reaches the stage of loss of tissue, whether through new tissue formation and contraction, or through destruction and cavity formation. I look upon it as being an expression of nature's attempt to equalize the atmospheric pressure within the lung and that upon the surface of the chest as described more fully on page 282. Compensatory emphysema is a dilatation of the air cells. In tuberculosis it affects the tissues which are most free from infection, those which are most useful to the patient. Where one lobe is the seat of cavity or marked fibrosis, a marked de- gree of compensatory emphysema will usually be distributed over a considerable portion of the remaining pulmonary tissue. If both upper lobes are the seat of destructive change, the bases are emphysematous ; and if one entire lung is involved in the de- structive process the other lung becomes emphysematous. Em- physema distorts the lobes and displaces their boundaries, as illustrated in Fig. 40, page 286. This condition is sometimes spoken of as an hypertrophy of the lung, rather than an emphysema. It is not primarily an emphysema in the sense that it is a degeneration of the alveolar walls, neither is it an hypertrophy in the sense of it being an increase in tissue, such as we see in the heart muscle for in- stance. I very much doubt if it is wholly what we have taught — an enlargement of that portion of the lung which is still able to functionate as a result of nature's effort to compensate for the parts destroyed — but look upon it as a compensatory enlargement of pulmonary tissue in order to fill the thoracic cavity. It oc- 494 PHYSICAL EXAMINATION IN PULMONARY TUBERCULOSIS curs in consequence of an attempt to preserve an equilibrium be- tween the atmospheric air as it presses upon the surface of the chest and as it presses on the air cells from within through the trachea and bronchi. The result is a dilatation which to all ap- pearances is an emphysema. The extra work thrown upon it is due to the loss of tissue, but it is not a cause of the dilatation of the air cells. If the compensatory change is to be looked upon as an attempt on the part of the lung to better carry out its func- tion, the emphysema is a mistake because the dilated air cells are not functionally as capable as the normal cells. Inspection. — It can readily be understood that compensatory emphysema, with its distended air cells and its pressure on sur- rounding structures, will, if well marked, cause alterations in motion and bulging of the thoracic walls from which its presence may be suspected. If of slight degree no change may be noted on inspection. By carefully inspecting a chest which is the seat of marked compensatory emphysema one can often form a fairly accurate impression of the pathological changes within the lungs. In generalized emphysema in lungs which are not the seat of destructive processes, the anteroposterior diameter of the chest increases, the lower ribs become elevated, the costal angle wid- ens, the diaphragm becomes displaced downward, and the mo- tion of the thoracic walls is decreased. Compensatory emphy- sema on the other hand is confined to limited portions of pul- monary tissue, because there is a decrease in the total pulmonary area. The air cells which are not destroyed are involved in the emphysema. They are dilated, and yet, in spite of this, they are compelled to aerate the blood. Consequently, all inspiratory effort is directed toward the emphysematous areas as being the parts which are not destroyed; consequently these portions of the chest often take upon themselves an increased movement. Localized areas of bulging with increased motion are very suggestive of compensatory emphysema. When one lung is the seat of marked destruction and the other is markedly emphysematous, the aux- iliary muscles of respiration are called upon for extra work and so stand out plainly on inspection. This is particularly true of the sternocleidomastoideus and scaleni. Under such circum- COMPENSATORY EMPHYSEMA 495 stances, too, we sometimes see the supraclavicular fossa swell up on forcible cough. One must not mistake the increased tone in the neck muscles in the presence of emphysema for reflex muscle spasm., Palpation. — Palpation over areas of compensatory emphysema shows tense intercostals, increased tension of that portion of the lung affected, and usually increased movement. The total density, as determined by the resistance to the palpating finger, is less than normal, where the pleura is normal and less than would be expected where covered by thickened pleura, or where previously or secondarily the seat of infiltration. Palpation shows the borders of the emphysematous lung to be pushed out- ward. Many times the diaphragm and mediastinum are pushed far from their normal position, as described on pages 285 and 305. Percussion. — Percussion shows hyperresonance, and where in- trapulmonary tension is high, tympany; although these sounds are greatly modified by other conditions present, such as thick- ened pleura and infiltrations. Lessened resistance is also pres- ent, less than that over normal lung when neither infiltration nor thickened pleura are present. Auscultation. — Emphysema shows many changes in the re- spiratory sounds. Sometimes the note is weak; but this is more apt to be the case in generalized emphysema than in the com- pensatory form. When the note is weak in compensatory emphy- sema it is usually because of thickened pleura, for the note is usually exaggerated because of the extra work thrown upon the part. The characteristics of the respiratory sound in compensatory emphysema are a roughened inspiratory note which often par- takes of or gives way to a harshness as the inspiratory effort becomes more intense and the note becomes more exaggerated; and a prolongation of the expiratory note due to the slowness with which the emphysematous lung completes the expiratory phase. The prolonged nature of the expiratory note is often overlooked by not listening intently through the entire expira- tory phase of respiration. It has often seemed to me like the contraction of the tense thoracic muscles has much to do with the character of the in- spiratory note in this affection. In this connection Kingston 496 PHYSICAL EXAMINATION IN PULMONARY TUBERCULOSIS Fowler 2 states, in discussing emphysema in general: "In place of tliis normal vesicular murmur audible on inspiration, the continuous low pitched rumbling sound produced by the con- traction of the muscles is very distinct." Dry Pleurisy. — Dry pleurisy is a frequent accompaniment of advanced tuberculosis. It comes at times as a localized process accompanying an area of caseation near the pleural surface; again, it manifests itself as an acute inflammation more or less widespread involving the subpleural tissues or pleural surfaces. Either process may result in adhesions. Inspection. — A marked limitation of movement on the side of the inflammation is usually evident to the eye, particularly if the process is near the bases. Palpation usually detects an increased tone (spasm) of the in- tercostal muscles which often feel decidedly boardy. It may also detect a pleural rub. It likewise confirms the limited motion noted on inspection. Percussion is practically valueless. Auscultation will reveal moist rales over the pulmonary focus when the pleurisy is due to active caseation of a subpleural pul- monary focus. It will also detect a pleural rub or roughness when the surfaces of the pleura are inflamed. A grating sound may be heard at times for some time after the acute symptoms disappear. Pain is usually a symptom and of itself is often sufficient for diag- nosis. Pleural Effusion. — Pleural effusion now and then complicates advanced tuberculosis. This complication is found comparatively infrequently in patients who are cared for properly. It seems that there is something in the general tonic treatment especially when fortified by tuberculin that makes effusions rare. The symp- toms and physical signs vary with the size of the effusion. Inspection. — Effusions when large may be suspected or even di- agnosed by the bulging ribs and interspaces on inspection. Dys- pnea may be present. The bulging of the ribs, limited motion, and displacement of the heart to the opposite side in the absence of symptoms pointing to pneumothorax, suggest effusion. Palpation. — Palpation shows increased resistance over the fluid 2 Allbutt-Rolleston: System of Medicine, vol. v, 1909, Macmillan Company, Ltd., New York. PLEURAL EFFUSION 497 due partly to the increased tension of the intereostals and partly to the increased density caused by the fluid. The outlines of the fluid can be detected by light touch palpation as readily as by percussion. Voice transmission as determined by palpation and auscultation is diminished. Palpation also confirms the limita- tion of motion on the side. Percussion. — Percussion may show any condition from a slightly impaired note to a very dull one. It also reveals increased re- sistance to the finger. The data obtained, however, requires con- firmation and must be considered in conjunction with that ob- tained by other methods of examination. Groco's sign, which is a triangular area of dullness on the side opposite the effusion, is usually found, if looked for with sufficient diligence. It is most pronounced and easiest of detection when the effusion is large. Auscultation. — The data obtained on auscultation over the ef- fusion may be nothing more than a weakened respiratory note; but this is of value in conjunction with other data. There is apt to be an exaggerated note over the pulmonary tissue above if the effusion is large. Thickened Pleura. — The pleura may show any degree of thick- ening from one that is barely recognizable to one of several centi- meters. This is an extremely common condition in pulmonary tuberculosis. It is rarely that we find apical pleurae free; for, as the disease affects the surface of the lung the irritation extends to the pleural surfaces and adhesions and thickenings result. Ad- hesions are favored at the apex by the limited motion of the part. Likewise they are opposed at the bases by the extensive movement. When, through disease in the underlying lung or of the pleura itself, the respiratory movements are greatly limited, adhesions are favored. After adhesions have once taken place increased thickening is probably favored by the irritation resulting from the movements of the thoracic wall and their pull against the adherent pleurae. Inspection. — Inspection usually shows a limited motion which is most marked when the thickening extends to the base; but this differs in no way recognizable on inspection from limited motion from other causes, except, at times, the side seems to move as a 498 PHYSICAL EXAMINATION IN PULMONARY TUBERCULOSIS unit. The wasting of the soft tissues over areas of thickened pleura of long duration is often plain to the eye. Palpation. — Palpation gives the most reliable information that we have in determining thickened pleura. It not only confirms the lack of motion but it reveals an increased density of the pal- pated tissues varying with the degree of thickening, and shows by the peculiar characteristics of the soft tissues (skin, subcuta- neous tissue, and muscles) overlying the pleura that there is a pathological condition underlying. Degenerative changes take place in the overlying muscles as described by Coplin 3 which give very valuable diagnostic data on palpation. (See Volume II, Chapter XXV.) The soft tissues overlying the thickened pleura lose their elasticity and feel lifeless and doughy. The tissues feel to the touch somewhat like those affected by a very slight edema. Later the subcutaneous tissue and intercostals degenerate and at times contraction takes place, drawing the intercostal spaces nearer together. Bonniger 4 has described a unilateral lymph-stasis as affecting the skin, subcutaneous tissue, and muscles over dis- eased pleurse. He states that the tissues appear to be increased in volume and firmer than normal. He mistakenly offered this as an explanation for the spasm of the muscles which occurs in the presence of active disease in the pleura and lung. In this he un- doubtedly recognized the doughy, inelastic, lifeless condition which I have described. Percussion. — Percussion alone gives nothing distinctive of thick- ened pleura. It reveals by a higher pitched note, a slightly de- creased resonance and an increased resistance to the finger that there is an increased density of the tissues underlying. "Which tissues are responsible for the changes can only be determined by considering the data, together with that obtained by other methods of examination. Auscultation. — Auscultation over thickened pleura will show varying degrees of diminished breathing; but since this complica- tion is usually associated with infiltration of the underlying pul- monary tissue, and since this of itself often causes diminished breathing, a weakened respiratory note must not necessarily be considered as due to thickened pleura. Other signs such as those 3 Changes in the Intercostal Muscles and the Diaphragm in Infective Processes Involv- ing the Lungs and Pleura, American Journal of Medical Sciences, May, 1904. 4 B6nniger: Ober halbseitige Lymphstauung bei Erkrankungen des Lunge bzw. Pleura, Berliner klinische Wochenschrift, Nr. 25, June 20, 1910. MEDIASTINAL THICKENING 499 determined on palpation should be looked for. Sometimes when the pleura is thickened there are many adventitious sounds present which accompany both phases of the respiratory act. They may sound like medium rales, but, for the most part, are dry in char- acter. They are apt to start with inspiration and continue until the end of expiration; and they give the impression of being near the stethoscope. Where these originate is not definitely settled but we are safe in saying that they originate either in the muscles or tissues which make up the thickened pleura, or in both. Mediastinal Thickening. — The mediastinum is a region which has been far too much neglected in clinical medicine. Prior to the use of the x-ray it was considered almost impossible to diag- nosticate pathological conditions in this part of the thoracic cavity, except they were of the most evident type. But, after obtaining a more definite idea of the processes which affect the mediastinum most commonly, we are now, clinically, either with or without the aid of the x-ray, able to examine this field with a fair degree of satisfaction. The mediastinum is a fruitful field for study in tuberculosis and particularly in advanced tuberculosis. It at times shows fibrous thickening which is important in the causation of symptoms even when the disease of the pulmonary tissue has not been suspected. Enlargement of glands, which often belongs to the stage prior to the pulmonary involvement persists and is evident on careful examination in from 20 to 25 per cent of cases. Adami and Mac- Kea 5 say that one-fourth of all healed cases of pulmonary tuber- culosis show enlarged bronchial glands. That type of tubercu- losis which starts at the hilus and extends out into the pulmon- ary tissue really belongs primarily to the mediastinum. Tumor masses of non-tuberculous nature, either solid or aneurism, at times complicate tuberculosis and must be looked for. Aside from these thickenings, the shifting of the mediastinum is ex- tremely important and deserves careful study. (For a more complete description of this see page 285. Fibrous thickening of tissue in the mediastinum as it occurs at times in advanced pulmonary tuberculosis, in my experience, is accountable for several direct symptoms, differing according to the nature of the case. transactions of the Sixth International Congress for Tuberculosis, 1908. 500 PHYSICAL EXAMINATION IN PULMONARY TUBERCULOSIS In a few cases hoarseness is a marked symptom; depending on the extent to which the laryngeal nerves are irritated. Cough, coming on in asthmatic paroxysms, is not uncommon. It may have a brassy tinkle. Bronchitis is often a common accompani- ment and is usually of a stubborn nature. Inspection. — As a rule inspection shows nothing definite as to thickening which occurs within the mediastinum. Occasionally, tumors, if large, may be suspected, by bulging of the thoracic wall. Palpation. — Palpation and percussion are our most valuable measures in diagnosis. By palpating over the sternum and ver- tebral column one will learn the usual degree of resistance which marks the normal mediastinum ; and will be able to detect any in- creased resistance due to pathological changes. New tissues, when present in the mediastinum, may belong to the tissues normally there or to pathological processes extending out from the pulmonary parenchyma; and the findings will vary accordingly. Anteriorly, the feelings of increased resistance will be under the sternum in the former case, while they will push out beyond its borders in the latter. It is well after palpating the sternum, to commence out in the interspaces and gradually ap- proach the sternum, then repeat the same over the ribs. Any re- sistance should be noted. On numerous occasions I have been able to suspect pathological deposits of fibrous tissue adjacent to the hilus which were confirmed by the x-ray, simply by noting the de- parture from the normal in the resistance to the palpating finger. Posteriorly, by straddling the spinous process with the first and second finger, as shown in Fig. 16, page 115, and, beginning above, palpating downward, one will learn to detect abnormally increased resistance, if present. Usually, if due to peribronchial and peri- tracheal glands, it will be detected at the level of the third dorsal vertebras. This increased resistance as a rule continues into the heart resistance, which normally begins in the average adult with the sixth dorsal. The resistance is nearly always greater on the right than on the left side of the spine because of the local- ization of the trachea on that side. It must not be forgotten, how- ever, that a certain amount of shifting of the mediastinum is com- mon in advanced tuberculosis and that it affects the position of the glands. MEDIASTINAL THICKENING 501 Percussion. — Percussion also shows the increased resistance to the finger though probably it is not as sensitive as palpation. Fred- erick T. Roberts 6 recognizes the value of resistance in percussion as follows: "It is highly important in relation to mediastinal tu- mors to bear in mind when carrying out the method of percus- sion, not only the sounds which are elicited, but also the sensa- tions which are felt by the fingers during the act. Not un- commonly the latter afford most valuable information." Per- sonally, while practicing both, I deem the resistance of greater value. Percussion over mediastinal thickenings will usually show an impaired note. It may be of any degree of dullness or even flat, according to the amount and nature of the tissue present. John C. da Costa, Jr., 7 in a careful study of dorsal percus- sion in enlarged tracheobronchial glands, states that in 18 cases carefully studied he found the following four groups of physical signs : 1. Interscapular dullness, above the level of the inferior scapu- lar angles, or over the first seven thoracic spinous processes. To this group belonged twelve or two-thirds of the cases. 2. Infrascapular dullness, below the level of the inferior scapu- lar angles, or over one or more of the five lower spinous tips. To this group belonged two cases. 3. General thoracic hyperresonance over the entire thoracic segment. To this group belonged three cases. 4. Normal percussion signs in the entire thoracic segment. To this group belonged one case. From this study it can be seen that sound alone is not the best criterion by which to judge of the presence or absence of enlarged mediastinal glands. Auscultation. — Auscultation is of little value in diagnosis ex- cept in cases where the new tissue is of such a nature as to con- strict a bronchus, in which case weakened breathing in the part affected may be detected, or where the enlargements stand in such relationship to the chest wall as to cause increased transmission of the breath sounds. 'Mediastinal New Growth, Allbutt-Rolleston: System of Medicine, vol. v, 1909. 'Dorsal Percussion in Enlargements of the Tracheobronchial Glands, American Journal of the Medical Sciences, November, 1913. CHAPTER XVni. TUBEECULIN TESTS IN DIAGNOSIS. General Considerations. — Now that we have at our command several different methods of making the tuberculin test, and are gradually learning their limitations, we have arrived at a place where we can state with increased definiteness the value of these measures. Years ago, when the diagnostic value of tuberculin was first learned, the subcutaneous was the only tuberculin test known. It was believed that a reaction to a dose of 10 mgs. or less of Koch's Old Tuberculin was positive evidence of the presence of clinical tuberculosis; and that a failure to react to 10 mgs. at least, if it were repeated once later, was a definite sign that tu- berculosis was not present. At that time the frequency of tuber- culous infections as we know it today was not known. A great prejudice against the use of tuberculin as a diag- nostic measure soon arose because of the severe reactions which attended it; so, the tuberculin test did not make great headway until other forms of employing it were discovered. In 1907 von Pirquet announced the cutaneous test. This was soon followed by the announcements of Wolff-Eisner and Cal- mette, of the conjunctival test, by Moro of the percutaneous, and by Manteaux of the intradermal. While other forms have also been suggested ; yet these are the ones which have been employed to the greatest advantage. They have helped greatly to popu- larize the use of tuberculin in diagnosis, although they have also added considerable confusion on account of the different opin- ions as to interpretation. When the cutaneous test was applied generally to children it was found that a very large proportion of them reacted promptly. It shows that most children are already infected with tubercu- losis by the time they reach their fifteenth year. This fact has TUBERCULIN TESTS 503 caused great confusion and challenged the worth of all tuber- culin reactions in adults, though I believe unjustly. All tuberculin reactions, except the general reaction, are anti- gen-antibody or immunity reactions. The general reaction, on the other hand, is a toxic reaction as described more fully in Volume II, Chapter XL. Immunity reactions are an expres- sion of the reaction which occurs between the specific ferments or antibodies which are called into being as a result of the stimu- lation of the body cells by the tuberculin introduced into the tissues. Whenever an inoculation, but particularly an infection with tubercle bacilli takes place, the cells of the body of that individual are so changed that they are sensitized against fur- ther attacks of the tubercle bacillus and its products; conse- quently the general opinion of the tuberculin reaction being evi- dence of active tuberculosis has gradually changed and in the minds of most clinicians the fact that an adult reacts to tuber- culin has gradually lost its significance. This change in atti- tude toward the tuberculin tests is not wholly warranted; but our newer knowledge shows that reactions must be more care- fully interpreted. While a tuberculin reaction will occur as long as the cells are sensitized to the products of the tubercle bacillus (as long as specific defense is present) and as long as they are active in producing specific antibodies against the tuber- cle bacillus, yet there is a recognized difference in the manner in which the body cells respond when fighting an active infec- tion as compared with a quiescent or healed lesion. Observa- tion has led me to believe that these reactions differ greatly and are of decided value. I have endeavored to interpret reactions, particularly the skin reaction, according to certain recognized principles in the establishment of immunity, and, while there are many times when it will not give the desired information, yet it will help as often as most measures in diagnostic use. It is most reliable in persons whose health is not undermined, because a positive reaction depends on the body cells having their normal reacting capacity and being able to respond with specific cell sensitization and with the production of specific antibodies when brought in contact with the tubercle bacillus or substances derived from it. The body cells are most active 504 TUBERCULIN TESTS IN DIAGNOSIS in defense during the time when they are fighting active infec- tion, and less active when this infection has become quiescent or healed. With these facts before us we are justified in believing that this difference in degree of specific cell sensitization (specific cellular defense) shows in the manner in which the cells react to tuberculin. Active tuberculosis, being accompanied by marked cell sensitization, responds quickly and markedly to the tuberculin test, while quiescent or healed lesions respond lightly and slowly. This I have found clinically. Those pa- tients who are suffering from active tuberculosis, as diagnosed by other methods, respond, as a rule, to the skin test, promptly, reaching the maximum of their reaction within the first twenty- four to thirty-six hours; while those in whom the disease is quiescent or partially so, respond to a less degree and more slow- ly, the maximum reaction being reached somewhat later if it ap- pears as more than a very slight reaction. In a patient with suspicious clinical history and a prompt maximum tuberculin reaction, I would be inclined to make a diagnosis of active tuber- culosis, whether physical examination reveals the focus or not. If, on the other hand, I found a negative reaction under these circumstances, or only a slight reaction, and the patient's physi- cal condition was such that I would expect a marked reaction in the presence of an active lesion, I would be inclined to feel that the patient was free from activity. A failure to react, or a slight reaction in one whose general condition is far below par, would not influence my opinion in the least. One difficulty in making diagnoses is that we lose sight of the fact that tuberculosis is often concealed. Clinical symptoms of tuberculosis might be present and, yet, upon physical exam- ination nothing be found that would make one suspicious of the lung being involved. The lesion might be in the mediastinal glands or any other glands or tissues of the body. I do not doubt that a great deal of our distrust and error in diagnosis of tuberculosis is due to this very fact. We are always expect- ing to find it as a pulmonary involvement, when it may be an involvement of any one of many organs. If we come to the point of recognizing tuberculosis as such no matter where found (and that is the way we should recognize it; at least we should TUBERCULIN TESTS 505 recognize active tuberculosis as active tuberculosis whether it be in the bone, or the joint, or lung, or wherever found) then we would be making real genuine progress in diagnosis; but, as it is today, if we are not allowed to make a diagnosis of active tuber- culosis unless it be in some portion of the body where it is going to seriously interfere with function, such as in the lungs, men- inges, bones, joints, or peritoneum, and if we are to ignore it when in the hidden glands, simply because we cannot see the focus, then we are going to continue to be greatly confused in trying to harmonize physical findings, clinical history, and the various reactions. Syphilis is syphilis no matter where we find it, and a positive Wassermann demands treatment. This is rec- ognized by all authorities whether the site of the lesion is found or not. Why consider syphilis so dangerous and ignore tuberculosis, or wait for it to manifest itself in some important organ before giving the patient the benefit of scientific treatment? The results of such a policy are shown by the death rate. It is necessary to bear in mind in employing tuberculin in diagnosis that the reactive capacity of different tissues and dif- ferent patients as well as that of different tuberculins and different preparations of the same tuberculin differs. Sometimes patients will not react to tuberculin even though tuberculosis is present. Such patients, as a rule, are in a low state of vitality and have built up no specific resistance to the tubercle bacillus ; or, if they have, it is in abeyance at the time. This is particularly noticed in the use of the skin test in persons suffering from acute infec- tious diseases, such as diphtheria, whooping cough, scarlet fever, meningitis, and particularly measles; and it is true of all tests to some extent in persons suffering from fever and cachexia and those who are in a low state of vitality. The subject of the relationship of hypersensitiveness to the character of the lesion, has been discussed from the experi- mental standpoint by A. K. Krause. 1 In these experiments he shows that the nature of the reaction depends upon the activity of the disease. This is in accord with the observations which I have made clinically and discussed previously. I wish to quote Experimental Studies on the Cutaneous Reaction to Tuberculo-Protein, Journal of Medical Research, New Series, vol. xxx, September, 1916. 506 TUBERCULIN TESTS IN DIAGNOSIS his general conclusions based not only on his own work but that of Baldwin and Romer, which are as follows: 1. "There is no cutaneous hypersensitiveness without a focus (tubercle). 2. "This hypersensitiveness appears coincident with the estab- lishment of the focus. 3. "It diminishes with the healing of the focus. 4. "It varies directly with the intensity of the disease, which in its turn is dependent on the virulence of the invading bacil- lus." The Subcutaneous Test. — Koch's Old Tuberculin is employed in making the subcutaneous test. While any tuberculin may be used, yet there are certain reasons why Koch's Old Tuber- culin is best. The tubercle bacillus is made up, or is capable of being divided into many different substances which Much has characterized as partialantigens ; for example, there are sev- eral different proteins, also several different fats that can be derived from it. The preparations of tuberculin are made in different ways and contain these various partialantigens in different proportions; in fact, in certain preparations some of these partialantigens are almost wholly wanting. The tissues of patients suffering from pulmonary tuberculosis contain anti- bodies to these different partialantigens in different propor- tions; in fact, sometimes antibodies to some of them are almost wholly wanting; consequently, in our choice of a tuberculin for diagnostic purposes we should employ one that contains the greatest number of partialantigens. Koch's Old Tuberculin fills this description best of all preparations, and consequently is the one we shall discuss. If several different forms of tuberculin are used at the same time in making the test, the reactions from the different preparations are not always uniform, as can be readily understood; but a reaction to any form of tuberculin is proof that antibodies to the particular partialantigens pres- ent in the preparation exist in the body tissues and such reac- tion is of diagnostic importance. It is further probable that, unless the patient has been inoculated with that particular partialantigen, the specific antibodies present are there, as a re- sult of a tuberculous infection. SUBCUTANEOUS TEST 507 The dilution of tuberculin for the test is simple. Dilutions should be made fresh at the time of each dose; or at least at intervals not longer than ten days, because the weaker dilu- tions do not remain active indefinitely. The original solution, however, if tightly corked, may be kept for a long time without losing its strength. Dilutions may be made by a graduated pipette or syringe. As a diluent, normal salt solution, plus two-fifths of one per cent carbolic acid is used. Two dilutions of the original tuber- culin should be made. One a 1 :100 is made by taking 0.1 c.c. of original solution and diluting it with 9.9 c.c. of the diluent. Of this solution 0.1 c.c. equals 1 milligram (0.001 c.c.) of tu- berculin, and a syringeful or 1 c.c. equals 10 milligrams (0.01 c.c.) of tuberculin. To make the 1 :1000 dilution, 0.1 c.c. of the 1 :100 dilution should be taken and diluted with 0.9 c.c. diluent. Of this dilution, 0.1 c. c. equals, 0.1 milligram (0.0001 c.c) of tuberculin, and 1 c.c. equals 1 milligram (0.001 c.c.) of tuberculin. These two^ dilutions are sufficient, because from them we can conveniently measure the doses, ranging from 0.1 mgm. to 10 mgms., which are ordinarily used in making the test. Temperature. — Preparatory to administering the subcutaneous test, a period of observation of the patient is essential. During this time, the patient should live as carefully as possible, saving himself from all unnecessary work and worry. It is best to have the patient confined to bed both during the period of ob- servation and the time that the subcutaneous test is being made ; but it is not essential, and cannot always be carried out, especially in clinic patients. It is essential, however, that the patient live under the same conditions during the period of observation and the making of the test. If he is in bed during the time of the test, he should be in bed during the period of observation. If he is to be up and around during the test, he should be the same during the period of observation. It is also essential that a record of the temperature and pulse be kept during both the period of observation and during the period of making the test. This should be made accurately. The temperature should be recorded at least four times a day, preferably on awakening in the morning, at twelve, four and 508 TUBERCULIN TESTS IN DIAGNOSIS eight o 'clock. The thermometer should be held in the mouth suf- ficiently long to guarantee full registration. This should be at least five minutes; and if the weather is cold and the patient is surrounded by cold atmosphere, it should be longer because it will often take ten minutes or more to warm the mouth so as to secure full registration. During the time that the patient is holding the thermometer he should not talk, because opening and closing the mouth interferes with accurate registration. It is best to administer the tuberculin at night so as to have the opportunity of observing any rise in temperature that would follow during the succeeding day. The temperature reac- tion usually begins sometime between eight and sixteen hours after the injection, so the rise in temperature is usually found during the succeeding day if the test is given at night. The re- action time, however, varies greatly under different circumstances. The subcutaneous test is applicable to any patient who is in an afebrile condition or any patient who is running a slight de- gree of temperature. As a rule, if the temperature is above 99.6° or 100°, it is not applicable. In fact, in a patient who is having a daily maximum of 99° to 100°, the diagnosis, if due to tubercu- losis, should usually be made upon clinical history and physical examination if the disease is in the pulmonary tissue or some other part of the body that is accessible. If not, some other form of the test should be used. If temperatures above that mentioned are due to tuberculosis it means that there is a considerable de- gree of activity present ; and, if marked activity is present, a tu- berculin reaction such as that which is apt to follow the injec- tion of tuberculin for the test, is best avoided; although I can hardly conceive of a single tuberculin reaction producing any serious trouble. It has also been said that this form of test is not particularly applicable in hysteria because the patient may become excited and suffer a rise of temperature from the nervous state, which might be mistaken for the reaction. If the peculiar character- istics of the tuberculin reaction, however, are remembered, it will be seen that there is a difference between the rises of tempera- ture from tuberculosis and those due to other transitory con- ditions. It will further be seen that any rise of temperature due SUBCUTANEOUS TEST 509 to a tuberculin reaction is usually accompanied by the chain of symptoms which make up the general reaction. In suitable cases for the test, that is, in slight infiltration with- out much temperature, no matter where the lesion is located, ex- cept in the meninges, the subcutaneous test is practically without danger. The injection may be given in any portion of the body. For convenience, however, I am inclined to use the forearm, upper arm, or sometimes the back. The question of dosage is an important one although it might not seem so from the variance in methods in vogue. There is much diversity in methods of administering the subcutaneous test. Koch suggested three doses, 1, 5, and 10 milligrams, the latter to be repeated in case of failure to react. These to be given with two or three days intervening between doses. The writer's method of giving tuberculin in diagnosis is as follows : The dos- age is gauged according to the earliness of the lesion, the tissue involved; the degree of activity suspected; and the physi- cal condition of the patient. If the lesion is early and inclined to be active, smaller doses should be used than in case it is more extensive or the lesion is fairly quiescent. If the patient is re- duced in vitality, smaller doses are employed than if the patient is stronger. In a child the dose is reduced from one-tenth to one-half that given to an adult. For the average adult my initial dose is one milligram. Two days later, if there is no re- action, I give 3 or 5 milligrams; three days later, in case of no reaction, I give 7 or 10 milligrams, according to the condi- tions. If the patient is a child, or one whose vitality is lowered, I would generally begin with one-tenth, then 1, 3, and 5 milli- grams. While a patient might react to 10 who does not react to 5, for the sake of safety higher doses are rarely employed. Nearly all patients suffering from early active tuberculosis will react to 10 milligrams if the proper increase and spacing of doses is followed. A positive reaction to a subcutaneous injection of tuberculin may show in three ways, by local, focal, or general phenomena. The local reaction consists in an irritation at the point of injec- tion. While this, of itself, is not generally considered as a posi- 510 TUBERCULIN TESTS IN DIAGNOSIS tive reaction in this form of the test, in reality it is as much so as any other local reaction. The focal reaction is a reaction in the tuberculous focus re- sulting from the combination of substances found in or elaborated from the tuberculin with the sensitized cells about the tuber- culous focus; or as a result of specific antibodies, whose forma- tion is stimulated by the introduction of tuberculin, combining with the products of the tubercle bacillus found in the focus of infection. The phenomena which appear are such as accom- pany any non-specific inflammation. If the reaction is light, a slight hyperemia only occurs, but if it is severe, the signs of a more serious congestion with exudation appear, accompanied by an increase of the usual signs and symptoms which previously existed. If the focal reaction is in a pulmonary focus it may be ac- companied by a cough even when one had not existed previously ; or an increase if it had previously existed. An exaggeration of the signs on auscultation may also take place, and fine rales may be increased or brought out where they had not previously been detected. The detection of a focal reaction in the lung, how- ever, is not an easy matter, and is of little use to anyone but an expert stethoscopist. In visible tuberculous ulcers, such as those in the larynx, the focal reaction may be seen as an in- creased hyperemia; in glands it sometimes shows as an increase in the size, with pain, swelling and redness ; in the kidney, pain, increased bacilluria, or hematuria may occur rarely, but must not be expected. In fact, the focal reaction, while giving more positive information, is, in the main, misleading and disappoint- ing. It does not always occur following the doses administered. A general reaction is accompanied by the same toxic symp- toms as are noted when activity is present in a tuberculous focus, and these symptoms differ in degree the same as they do in the clinical disease. There may be a slight drowsiness, a feeling of heaviness, a tired feeling, or an aching, either slight or amount- ing to extreme discomfort, such as accompanies acute infection (tonsillitis or la grippe). The patient experiences an increased nervousness, sometimes insomnia. When the reaction is severe, a chill and even vomiting may precede a rise of temperature. SUBCUTANEOUS TEST 511 The temperature rise was formerly made the sole means of judg- ing the subcutaneous test, and an elevation of two degrees was demanded for a positive reaction. This is no longer necessary, for those who have had experience have been able to demon- strate that the chain of symptoms previously mentioned almost always manifest themselves with a dose short of that which causes the two degree rise in temperature. The lighter symp- toms also mentioned will sometimes appear without a rise in tem- perature, or with a rise of only a fraction of a degree and are just as specific. The effect of intercurrent troubles in producing similar symptoms must be considered, should any such arise. The diagnostic value of the general reaction, which is more properly called the toxic reaction, depends upon the presence of specific proteolytic enzymes. When a small quantity of tuber- cle protein is injected parenterally into the body of a non-tuber- culous subject, no recognizable signs of reaction follow, because the process required for its destruction is a slow one, and the toxic molecules are set free very slowly and in such small quantities that they are rendered harmless or excreted without producing recognizable effects. When injected into an indi- vidual who is infected with tuberculosis, on the other hand, specific proteolytic enzymes capable of splitting it up into less complex molecules, are already present, and act upon tuberculin as soon as they come in contact with it, setting free the toxic molecules rapidly and in large quantities. The character of the reaction depends upon the rapidity with which the toxic mole- cules are liberated; and this, in turn, depends upon the amount and activity of specific enzymes present. Inasmuch as these are present in greatest amounts, and most active, when the body is fighting an active infection, active tuberculosis, all other con- ditions being equal, reacts to smaller doses and more promptly than quiescent and healed tuberculosis. This gives the reaction its diagnostic value. The general reaction manifests itself as the syndrome of toxemia, which acts through stimulation of the cells of the cen- tral nervous system and is expressed chiefly as a general sympa- thetic stimulation. The cause of the fever, as described in Volume II, Chapter XXX, is not so much the increase in heat pro- 512 TUBERCULIN TESTS IN DIAGNOSIS duction as it is a stimulation of the vasoconstrictors which in- terfere with the elimination of heat from the surface of the body. The temperature following tuberculin has certain peculiarities which are almost diagnostic of themselves. If Koch's Old Tuber- culin is employed, and it is best, the temperature usually comes on sometime between eight and twenty-four hours after the injection. The temperature usually rises gradually. It may take twenty-four hours to reach its maximum and then it falls gradu- ally. I have never seen a reaction of more than a small fraction of a degree, which was positively due to tuberculin, in which the maximum temperature was followed in a few hours by a normal. The morning temperature on the day following a posi- tive tuberculin reaction is nearly always above the usual morning Fig. 98. — Three different temperature curves, illustrating tuberculin reactions. It will be noted that the temperature does not return to normal on the second day of the reaction. This is characteristic of the curve of the tuberculin reactions. register. The accompanying curve, from the author's monograph on tuberculin, 2 illustrates this point (Fig. 98). The Cutaneous Tuberculin Test (von Pirquet). — The cutaneous tuberculin test, which is commonly called the von Pirquet test, was brought forth by von Pirquet in 1907. He explains it as being a reaction of hypersensibility and due to a condition which he has described as allergy, from ergeia, meaning reactivity and alios, meaning altered. He means by this that in tuberculous patients the reactivity of the cells is altered from what it is in those who are non-tuberculous, and that this alteration mani- 2 Tuberculin in Diagnosis and Treatment, C. V. Mosby Co., 1913. CUTANEOUS TEST 513 fests itself in a specific method of reacting when tubercle bacilli or the products of tubercle bacilli are brought in contact with them. The cutaneous, like the subcutaneous test, depends for its diagnostic value upon the fact that the infected individual pos- sesses within his body specific proteolytic enzymes which rapidly split the protein molecule contained in the tuberculin into simpler molecules. While the subcutaneous reaction depends on the toxic molecule, the cutaneoius, along with the percutaneous, intra- dermal and conjunctival, depends upon the sensitizing molecule for its reactive phenomena. This reaction is more specific than the toxic reaction; in fact, the factor which makes the toxic reaction (subcutaneous) of any value at all in diagnosis, is the rapidity of the destruction of the tubercle protein, resulting in prompt liberation of the toxic molecule. The real diagnostic worth of the cutaneous test is not in the mere presence or absence of a reaction. Some evidence of sensi- tization should be expected in all patients who have harbored in- fection within their bodies. Clinical experience, however, seems to show that this gradually lessens until it may finally disappear after the infection has been healed for a term of years. The na- ture of the reaction, however, affords valuable diagnostic evi- dence. It gives an idea of the degree of sensitization present. If marked sensitization is present it suggests that the patient is, or has been recently, fighting active tuberculosis. Otherwise there would be no need for the presence of the large amounts of specific enzymes which are responsible for the reaction. I have gradually learned to suspect that the patient who re- acts promptly with a marked reaction reaching the maximum within the first twenty-four or thirty-six hours, does so because the body is well supplied with specific enzymes as a result of an unhealed focus. The degree of promptness of the reaction in this test, the same as in the preceding, depends upon the rapidity with which the tubercle protein is split, consequently, upon the number of specific enzymes, which are governed by the urgency of defense. Before making the cutaneous test, the skin should be cleansed 514 TUBERCULIN TESTS IN DIAGNOSIS with alcohol or ether and allowed to dry. The test is then made by placing a drop of the solution of tuberculin to be used, on the skin and producing an abrasion of the skin through the drop. This method is much better than to make the abrasion first and put on the tuberculin afterwards; because, by this method of making the abrasion, the tuberculin is mechanically pressed into the tissues and thus comes in surer contact with them. The scarifier devised by von Pirquet is much better than the scalpel because it is desirable not only to determine whether or not a reaction is present, but the degree of the reaction. This cannot be so accurately done when there has been considerable trauma, as often occurs when the scalpel is used. It is well to make a control abrasion without tuberculin, for the purpose of com- paring the traumatic reaction with the tuberculin reaction if present. In making this test, I, personally, prefer to use 100 per cent strength of tuberculin, although 25 per cent and 50 per cent may be used, if desired. I have never seen any harm from the 100 per cent and have found some positive reactions with the full strength which were more or less doubtful with weaker dilutions. Tests may be made anywhere on the body; but, for convenience, I prefer the forearm, although there are some reasons in favor of choosing a portion of the skin which is more delicate, such as that over the thorax. Sometimes the deli- cate skin will give a more marked reaction than the skin of those parts which are less sensitive. This test should be given in a definite manner. Its very sim- plicity often leads to a haphazard method of making it and this militates against its usefulness. The tuberculin should be brought into close contact with the subcutaneous tissue and should be al- lowed to remain in contact for a sufficient time for absorption to take place. Five minutes is usually sufficient. The patient should then be instructed not to allow the clothing to wipe it off. Some clinicians cover the abrasion with a gauze protection, but this is not necessary. Not only the reaction, but the strength of the reaction, and the time of its appearance should be noted. A positive reaction consists in an area of redness appearing at the seat of the inoculation. Sometimes it is only a slight red- ness of the tissue surrounding the trauma, which can hardly be .2B .2 A SA. 3B. Platb VI. 1. Conjunctival reaction of left eye. 2/4. Von Pirquet reaction, well marked; B, control site 3A. Von Pirquet reaction, moderate; B, control site. 4. Moro reaction, well marked. 5. Moro reaction, slight. PERCUTANEOUS AND CONJUNCTIVAL TESTS 515 differentiated from the traumatic reaction of the tissues. Some- times it consists of a papule which may even form a vesicle. Surrounding the papule there is usually an area of redness of varying extent, and at times the reaction can be traced out along the lymph channels for a distance of several centimeters. A very marked reaction may be four or five centimeters in diameter. It is possible that sufficient tuberculin may be absorbed to cause a temperature reaction in very sensitive individuals. Such in- stances have been reported but the writer has never seen it occur. Plate VI (3 a and b) illustrates the cutaneous reaction. The Percutaneous Test (Moro). — The percutaneous test is made by rubbing a mixture of equal parts of Koch's Old Tuberculin and lanolin into the uninjured skin. Of this an amount equal to the size of a pea is used. It is best to use some portion of the skin that is protected and sensitive. This test is not as reli- able as the cutaneous because of more or less error in securing absorption. The reaction usually occurs in twenty-four to forty- eight hours after the inoculation and shows as a number of small red spots, but if the reaction is severe they may take the form of small nodules lasting for several days. (See Plate VI, 4 and 5.) The Conjunctival Test (Wolff -Eisner). — The conjunctival test which was brought out by Wolff-Eisner and later by Calmette is gradually falling into disuse, owing to the more simple cu- taneous and percutaneous methods. Koch's Old Tuberculin is used for the test. Two dilutions are made, a one and a two per cent strength. One or two drops of the one per cent is instilled into one eye. If no reaction occurs, later a two per cent should be instilled into the other eye. A positive reaction is shown by the development of hyperemia. If the reaction is slight there is only a faint redness of the con- junctiva, but there may be a marked conjunctivitis, even puru- lent in character, if the reaction is severe. It should be used in any case where the eye is diseased, particularly if the disease is of a tuberculous nature. This reaction is shown in Plate VI, 1. The Intradermal Test is made by injecting a few drops of a dilution of 1-1000 or 1-5000 of Koch's Old Tuberculin between the layers of the skin. A positive reaction shows as an induration. CHAPTER XIX. THE X-RAY AS AN AID TO THE DIAGNOSIS OF PULMONARY TUBERCULOSIS. Relative Value of Physical and X-Ray Examinations. — The difficulty as well as the importance of early diagnosis of tuber- culosis reveals itself in the great number of methods which have been suggested to detect this disease during the period when the pathological changes are slight. The most important methods for the diagnosis of early clinical tuberculosis are the clinical history and physical examination of the patient. These two alone, if the history is taken with sufficient care and the ex- amination is made with sufficient skill, will determine the pres- ence or absence of tuberculosis in nearly all instances. As supplementary aids to these important measures, however, we have the examination of the sputum for bacilli, lymphocytes, and albumin; the complement deviation and opsonic tests; the tuberculin tests; and the x-ray. Each of these methods of ex- amination may become an important aid under certain circum- stances. This is particularly true of the examination for bacilli, the tuberculin tests and the x-ray. These supplementary tests, however, should be considered only as aids to diagnosis and should be used in conjunction with the clinical history and the physical examination. When the x-ray was first discovered it was hoped that a method had come into vogue which would give an accurate picture of all conditions within the thorax, but it was soon learned that such was not the case. It has taken a number of years to determine the relative value of the x-ray examination as compared with the clinical examination. Clinicians who have had most experience and are best able to judge are in accord in their opinion that an ac- curate clinical history and a skillful physical examination will reveal changes which result from tuberculosis earlier than can RELATIVE VALUE OF X-RAY EXAMINATION 517 be shown by the x-ray examination. From the practical stand- point, however, this is not the question of greatest importance. The question is : how may the x-ray be used to give the greatest aid in the diagnosis of early tuberculosis? "While the value of a skillful clinical examination cannot be questioned, yet it is but fair to admit that proper accuracy and skill are not always ap- plied. Cases of early tuberculosis will be found among every man's patients ; and every man who does any considerable practice will at times suspect tuberculosis. Many will overlook the disease because of their inability to make the clinical examination with sufficient skill. Diagnosis at such times will be facilitated either by a skillful clinical consultant or by having the aid of an expert radiographer. Even the men who make the most care- ful examinations find themselves puzzled now and then, and can be aided greatly by the study of an x-ray picture, particularly the stereoscopic picture made by one skilled in pulmonary ront- genology. It is important in this connection, to have in mind that the plate and screen are, at least equally and probably more likely to present inaccuracies than the careful physical examination. It must not be taken as an infallible picture, nor must its interpretation be taken as being without error. The practical question which confronts us in this discussion is : can a more general use of the x-ray result in causing diagnoses of pulmonary tuberculosis to be made earlier than they are being made by present clinical methods? The answer to this question cannot be given except by considering the relative skill of the examiners. It seems to me that whenever the skill of the ex- aminers is at all nearly equal, preference should be given to the personal clinical examination rather than to the impersonal x-ray plate. The human side of medicine must not be underestimated. The analysis of the case, the symptoms, the clinical course, and the data found on physical examination as belonging to and being a part of a process within a human being is all important. In other words, the ultimate diagnosis should be made by the cli- nician. However, the employment of an expert x-ray operator, the same as an expert clinical consultant by men who are not able, or at least by those who do not make careful chest examina- 518 X-RAY AS AID TO DIAGNOSIS tions, would undoubtedly reduce the percentage of error in diagnosis very materially. On the other hand, reliance placed on poor plates made by unskilled workers can only mislead. Such x-ray examinations are on a par with poor physical examina- tions, and cannot be relied upon. There has been considerable discussion as to whether or not active tuberculosis can be differentiated from healed tuberculosis by the x-ray picture, particularly when the lesion is young. Skilled operators who use up-to-date technic and who have most experience in chest work claim it possible to do so. Such diagnoses, however, should not be accepted without careful com- parison with the data found upon clinical examination. The earliest pathological changes in tuberculosis of the lung are not gross. There is no calcined tubercle, neither is there fibrous tissue. There are fresh tubercles surrounded by areas of exuda- tive inflammation of a mild degree. This condition is rarely diagnosed except by expert clinicians, and it is decidedly ques- tionable whether a shadow would be shown on the screen as a re- sult of it. The fluoroscope should show the altered motion of the diaphragm; and this, together with the changes in the tone (spasm) of the apical muscles should direct the examiner to the pulmonary involvement. Minor 1 says: "After having used the rontgen ray fluoroscopic- ally in all his examinations for the past seven years, the writer believes that in the majority of cases an expert physical diagnos- tician will be able to make a diagnosis of incipient tuberculosis sooner than will the radiologist; but, in a few cases, the latter will discover small foci of tubercle in the lung which neither auscultation nor percussion would reveal. There are certain pulmonary conditions, especially enlargements of the tracheo- bronchial glands and peribronchial infiltrations which can be diagnosed far earlier and better by this method than by any other. ' ' Gregory Cole 2 states that the x-ray plate, when properly in- terpreted, will make the diagnosis of early pulmonary tubercu- ^lebs: Tuberculosis, D. Appleton & Co., 1909. 2 The Radiographic Diagnosis and Classification of Early Pulmonary Tuberculosis, Amer- ican Journal of Medical Sciences, July, 1910. RELATIVE VALUE OF X-RAY EXAMINATIONS 519 losis earlier than either the fluoroscope or physical examinations. Vincent Y. Bowditch 3 says: "In spite of the great advance that has been made in the practical use of the x-ray of late years, I can but feel that we have not yet sufficiently studied the causes of the phenomena shown by this method to warrant our drawing what have seemed to me at times hasty conclusions as to the amount and nature of disease which may be present in the lung. One thing is absolutely certain in my mind, viz. : that I have very little faith in the findings of anyone but those who are experts in this department of science, but I must unhesitatingly condemn the diagnosis of those who, upon the insufficient ground of their own supposed findings in the use of the x-ray, give their patients unnecessary alarm and anxiety as to their bodily condition." Bonney 4 made a careful comparison of physical examinations and radiography and states: "As a result of this inquiry, how- ever, previous convictions as to the slight practical value of the x-ray in the diagnosis of very incipient cases without well de- fined structural lesions have been substantially confirmed." Heise and Sampson, 5 after an analysis of their own experience in ninety-five very early and difficult cases, take a very com- mendable stand on the comparative advantage of physical ex- amination and the x-ray, as follows: "1. When the history and physical examination were posi- tive, the x-ray showed a lesion in 77 per cent and failed to show a lesion in 23 per cent. "2. When the history and physical examination were nega- tive, the x-ray failed to show a lesion in 58 per cent and dis- closed one in 42 per cent. "3. When the history was positive and the physical examina- tion negative, the x-ray showed a lesion in 60 per cent and failed to show one in 40 per cent. "4. When the history was negative but the physical examina- tion was positive, the x-ray showed a lesion in 50 per cent and failed to show one in 50 per cent. 3 What the General Practitioner Should Know About Incipient Pulmonary Tuberculosis, Boston Medical and Surgical Journal, November 25, 1915. ^Pulmonary Tuberculosis and Its Complications, W. B. Saunders Co., 1908. "The X-Ray in the Diagnosis of Pulmonary Tuberculosis, Interstate Medical Journal, vol. xxii, No. 10, 1915. 520 X-RAY AS AID TO DIAGNOSIS "At first thought these results may seem to indicate that the x-ray has but little value as an aid in diagnosis. But when we consider that the basis of classification and the class of cases in which the comparison was used, the advantage that the x-ray affords is really obvious. In only 23 per cent of all were the history and physical examination both positive. In 35 per cent of the cases both history and physical examination were doubt- ful or negative. The history only was positive in 32 per cent and the physical examination alone was positive in 10 per cent. As the disease is more advanced naturally the percentage of definite lesions seen in the plate becomes proportionately greater. And it is a fairly common experience to find more extensive in- volvement upon x-ray examination than is detected by physical signs. At times the difference is so great as to be astounding. "Plates taken at intervals in the course of the disease will show marked changes in some instances and at times these changes are detected before physical signs have perceptibly al- tered. "In the differential diagnosis of mediastinal and lung condi- tions the value of the x-ray is unquestionable, but this phase of the subject will not be dealt with here. "In conclusion, we would like to state that in our opinion the x-ray in diagnosis can be made to give, as nearly as pos- sible without exploration or autopsy, evidences of the existing pathology in the lungs. It has been of distinct advantage in the diagnosis and better understanding of existing lesions in the lung, and with plates taken at intervals, changes for better or worse have been noted in the areas involved. Owing, however, to the fact that the x-ray is a shadow projector only, we do not think it infallible and that it should at the present time, at least, replace all other methods of diagnosis. Bather do we think it should be used in cooperation with all methods — as an aid rather than an infallible means." In using the x-ray it must be remembered that slight lesions produced by early tuberculosis may not produce sufficient changes in the density of the tissues to alter the shadow, and yet may be detected by expert physical examination. There are several portions of the lung which should be exam- INTERPRETATION OF PLATE 521 ined especially carefully for tuberculosis, although foci may ap- pear in any part. Thanks to the x-ray we have learned of the frequency of hilus infection. We have found it necessary to change our ideas of physical diagnosis and search for early tuber- culosis in wider areas than formerly. While the apex still holds its place as the common seat of early clinical tuberculosis, yet we commonly find infections near the hilus, running out into the tissue in all directions, but particularly toward the apex and the base. These hilus infections are especially difficult of detection on percussion and auscultation and here the x-ray has given great aid. Interpretation of Plate. — It requires experience to read and in- terpret x-ray plates. While there is room for much error in making the plate, one must not lose sight of the fact that the greatest skill and judgment is required to interpret the plate. We should expect the dense fibrous tissue of the healed tuber- cle and the calcified tubercle to interfere most with the penetra- tion of the rays, consequently we would expect the shadows cast by such structures to be more definite and clear cut than those produced by tissue of lesser density. On the other hand, we would expect active tubercles, which are surrounded by an exudative inflammation, whether isolated or conglomerate, to produce a hazy undefined shadow, and the latter particularly to show a mottling of the plate. The shadows cast depend on a great many things such as the character of the tube, the exposure, the depth of the lesion, and the chemical constituents of the focus. Assmann 6 made a careful study and comparison of x-ray findings and postmortem findings. He says: "At times the x-ray shows details of un- expected minuteness; for example, nodules scarcely as large as pin heads are at times shown, exact in position, size and rela- tionship. Again, nodules as large as walnuts fail to appear on the plate and areas of thickened tissue even larger than this, cast no shadows or shadows which are scarcely recognizable. Aside from the thickness and specific chemical composition of the focus, the detail of the shadow which it produces depends upon its depth in the tissues." 6 Erfahrungen iiber die Rontgenuntersuchnug der I- u-s; d - s < w - s ; bun > free. This form of report, while not very accurate for the individual case, gives considerable information in the aggregate. The dif- ficulty in interpreting such findings is due to the uncertainties incident to our homogenizing methods, variable penetration of stain and to the well known difficulty of securing smears of uniform thickness. For homogenizing, the mechanical shaker is indispensable. As to penetration of stain, there is considerable variation with which bacilli from different sputa are impreg- MORPHOLOGICAL CHARACTERISTICS OF BACILLI 565 nated. This is often noticed when two preparations are placed on the same slide and stained together. In one, the bacilli stain intensely and uniformly; in the other they are only well stained or pale. The latter, if washed with ether, on restaining will often take the stain as intensely as the other specimen does. In such sputa, after fermentation one will usually find consider- able neutral fat floating on the top of .the supernatant liquid. This seems to account for much of the defective staining, which is likely to be attributed to inherent differences in bacilli. This fat is usually easily traceable to food particles, — butter, milk, etc., where the patient is careless about cleansing the mouth after eating. Even after all other technical features have been carefully carried out, such as thorough homogenization, uniform tempera- ture during staining, definite time for exposure to stain, etc., one may obtain quite different descriptions from the same speci- men unless very careful to choose fields of the same thickness. Bacilli which appear narrow, beaded, well-stained, or pale in thick fields, are broad and deeply stained in very thin fields, and the beads may not be seen at all, or only slightly visible, being masked by the intense staining of the bacillary envelopes. The morphological characteristic which is most free from er- ror in recording is the relative length of the bacilli. From 50 to 80 per cent of all tubercle bacilli in all cases are from 2 to 4 microns in length; the remaining 50 to 20 per cent varying greatly in length. All may be less than 2 p. or they may be from 4 to 10 fi. in length; consequently, the average length of bacilli met with in different sputa shows striking variations. During the last year I have added to the above form of report a fairly accurate classification of bacilli based upon the length, from which is calculated an index in the following manner. Into the ocular is inserted a little brass frame upon which is mounted three glass beads which cast shadows of 2, 4, and 6 microns upon the microscopic field, using Bausch and Lomb eyepiece 1 inch or lOx, objective M.2th, focal distance 160 mm. (see Fig. 100). These glass beads are made by drawing out very fine glass filaments in the flame. They are then fused on the end in a very small flame, preferably from an alcohol burner. They are then standardized with the stage and eye-piece micro- 566 LABORATORY METHODS meters, and those selected which are of the desired diameter. Unfortunately the manufacturers do not make their oil immer- sion lenses exactly of the same magnification, so that one can- not use the device in different microscopes unless the ocular and objective systems are exactly the same. I have three B & L Y 12 oil immersion lenses, and the relative magnifying powers are 79.2, 75, and 71.4. This results in a variation of about 10 points in index in comparisons which I have made, between the first and last objectives. There would be a great advantage if the Fig. 100. — Device for classifying tubercle bacilli according to length. A, B, and C, fine glass filaments supporting glass beads which cast shadows of 2, 4 and 6 microns respectively, upon the microscopic field. method could be carefully standarized so that a given index would mean the same regardless of the instrument used. Because of the ease with which the device may be broken, I have attempted to find some substitute. A special disc was made by the manufacturer upon which were made three circular etchings of the proper size; but it was necessary to discard the device because the etchings did not show up plainly. With a little patience I believe that anyone familiar with micrometry LENGTH INDEX OF BACILLI 567 can manufacture the device for himself. I have used mine for fifteen months without breaking. Using a mechanical stage all bacilli that pass between beads 2 p. and 6 /x. are classified. This can be done quite rapidly, and in most preparations it is not necessary to orientate the beads, a glance being sufficient to determine whether a given bacillus is longer or shorter than the diameter of a certain bead. There are some preparations, however, that give considerable trouble, in which the greater number of bacilli are so near 2 fx. and 6 fx. in length that one is in doubt unless the bacillus is brought alongside the bead. Very thin smears only should be used. The bacilli must lie absolutely flat and not tilted as we find in thick fields. Even then there is some inaccuracy. A differential count of 500 should be made if possible. This reduces the error to a small figure. Length Index of Tubercle Bacilli. — The index is derived from the differential in the following manner: All bacilli less than 2 fx. in length are called short and are given an arbitrary value of 1. All between 2 fx. and 4 /x. in length are called medium. An arbitrary value of 2 is assigned. All between 4 fx. and 6 fx. are called long, with a value of 3. All longer than 6 /x. are called extra long with a value of 4. A count of 100 is the basis. 4 3 2 1 Differential Extra-long long medium short Inde Counts. 8 27 72 3 260 1 64 35 166 39 61 139 The index determined in this way is called the length index of tubercle bacilli. In over 600 differentials made the index varies from 130 to 264, — about 75 per cent of them lying be- tween 150 and 200. The index cannot be made safely from single specimens, nor from unhomogenized 24 hour specimens, as is shown by the following experiment: A patient with signs of considerable activity was instructed to separate his 24 hour sputum into three receptacles. He raised 35 c.c. from 8 :00 p. m. to 6 :00 a. m. ; 55 c.c. from 6 :00 A. m. to 9 :00 A. m., and 75 c.c. from 9 :00 A. m. to 8 :00 p. m. Two direct smears were made from each of the three portions, and the index determined from each. 568 LABORATORY METHODS The six indices were 180, 201; 185, 190; 187, 190. Although four of the indices accord splendidly, a variation of 180 to 201 can- not be allowed. The experiment has been repeated with other patients with essentially the same result. Comparisons after shaking 10 to 20 minutes show less varia- tion between duplicate counts. Two series of duplicate counts on different sputa gave the following indices: 214, 215; 165, 158. Several series of counts of four or five preparations from each specimen gave 156, 155, 161, 160, 153; 202, 208, 210, 217, 214; 223, 223, 221, 218. Although the index made from homogenized specimens is usually more accurate on the average than when made from unhomogenized material, at least 5 or 6 points should be allowed for error. URINE. The value of routine examination of urine in the study of tuber- culous patients is not appreciated as fully as it should be. The im- pression is too general that except in special instances, where some non-tuberculous complication is suspected, urine analysis offers little help to the clinician and is hardly worth the time required. Such records as are made are usually determined from single specimens which may give quite different information from what would be obtained if twenty-four hour specimens were ana- lyzed. For eight years I have made an analysis of a twenty-four hour specimen from each patient previous to the regular monthly physical examination. This analysis consists in the determina- tion of the specific gravity, the presence or absence of serum albumin, globulin, nucleo-albumin, mucus, reducing bodies, in- dican, and diazo. For the last two years the urochromogen test has also been made regularly. Formerly quantitative chloride and phosphate determinations were made, but later were discon- tinued as regular tests. Over 8,800 such analyses have been made. The tests which have been most useful are the diazo and indican tests. Collection of Specimen. — Formerly the twenty-four hour quantity was collected from morning to morning according to the well known directions, and, although the instructions were THE DIAZO REACTION 569 carefully given, there was often confusion in the patient's mind and errors were common; so that the time for starting and end- ing was changed to eight o'clock in the evening, since at that hour any possible error in voiding more or less than the proper amount would be less than in the case of a similar error in void- ing the more concentrated morning's urine. There is no great objection in allowing the urine to stand over night, as the substances tested for are relatively stable. Traces of albumin may, however, be formed by bacterial autolysis, hence the presence of albumin must be interpreted with this fact in mind. A few drops of chloroform are added to limit bacterial growth. The Diazo Reaction. — The diazo test is made with the usual reagents. Sol. I. One-half per cent sodium nitrite. Sol. II. Sulphanilic acid 5 gm. Hydrochloric acid 50 c.c. Distilled water to 1000 c.c. In making the test, one-tenth c.c. of Sol. I is mixed with each 5 c.c. of Sol. II. About 2 c.c. of urine is placed in a test tube one-half inch in diameter, and to it is added an equal amount of the reagent. The mixture is shaken briskly to develop a good foam. One-tenth volume of ammonia is now added and a pink color in the foam is looked for. The pink is often masked by an admixture of brown. In such cases doubt may be cleared by adding only one-half as much reagent as urine. In a series of tests on 48 consecutive urines in which 21 positive and 10 doubt- ful reactions were obtained by using equal volumes of reagent and urine, sufficient additional results were obtained by using 1/2 volume reagent to 1 volume of urine to make 29 positive and 6 doubtful reactions in all. "While the additional advantage given by the latter proportions of reagent and urine has long been known, it is undoubtedly overlooked in many laboratories. When the diazo is positive, the relative intensity is determined by diluting the urine and making the test again, always with equal parts of the reagent and diluted urine. The dilution at which the pink is just visible in the foam is recorded as the de- gree of intensity. One must be very exact in making the dilu- 570 LABORATORY METHODS tion and in measuring the urine and reagent, otherwise the re- sults may be inaccurate. In over 2,000 positive tests found in over 8,800 urines from 1,500 patients, diazos were found com- monly ranging from a doubtful reaction to one-sixth, rarely to one-seventh, one-eighth, or one-ninth. As the diazo is usually more intense in the afternoon than in the morning, positive tests have been found at that time in one-tenth and one-twelfth dilu- tions. Although the diazo reaction has been known for over thirty years, individuals will differ somewhat in deciding whether a given test is positive or negative. The pink foam is probably the most generally recognized criterion. Normal urines give a white foam if fresh, or a very light brown foam if the urine has stood for some time, or is concentrated. The solution below the foam ranges from light yellow to dark yellow, sometimes with a slight brownish tone, but never in my experience does it as- sume a reddish tone in a normal urine. When doubt exists as to the presence of a pink in the foam, I call the reaction a suggestion. Patients showing such doubtful reactions in the twenty-four hour urine will nearly always show a distinct diazo if an afternoon sample is called for. These doubtful reactions always show a reddish tone in the solution, although it may be partially masked by admixture of brown. The Urochromogen Reaction. — In announcing his permanganate test for the urochromogen body, Weisz considered the relative proportions of reagents and urine to be of little consequence. This fact gave it great advantage in his mind over the diazo test, in which care is required to use exact amounts of reagent and urine. He recommended to dilute the urine roughly with two parts of water in a test tube, and add three drops of potassium permanganate. The development of a yellow color was con- sidered a positive test. A number of observers following these instructions have arrived at widely different conclusions as to the relative sensitiveness of the urochromogen and diazo tests, and consequently as to their interpretation for purposes of diag- nosis and particularly prognosis in tuberculosis. All reports agree, however, that the urochromogen is met more frequently than is the diazo. Heflebower, Gullbring, Sinclair, and others found it from two to three times as often as the diazo, but THE UROCHROMOGEN REACTION 571 Schaeffle found it in only y± more cases than he did the diazo. Others found the relative occurrence of the two reactions lying between these extremes. From the simple instructions of Weisz, it is evident that two workers may make their tests with widely different proportions of reagent and urine, depending upon the size of drop of reagent and the amount of urine used. As it seemed that this might account for some of the differences shown in the reports, I un- dertook a detailed study of both urochromogen and diazo in a considerable number of fresh urines from normal persons and patients, and in twenty-four hour specimens from patients. The color of both foam and solution in the diazo was described. The urochromogen tests were made in a series of five tubes, each con- taining 5 c.c. of % dilution of urine. Using one tube as a con- trol, to the four tubes remaining were added successively, quantities of reagent corresponding to 5 drops, 3 drops, 2 drops and 1 drop, — this being the probable range of variation em- ployed by various workers. The changes of color were recorded in each tube at once, at the end of 15 seconds, of 30 seconds, 60 seconds, and 120 seconds. If either the diazo or urochromogen was positive on first trial, the urine was further diluted and the test repeated until the dilution was found in which the pink disappeared in the foam and solution of the diazo test, and the yellow disappeared in the urochromogen test. From this work it was found that yellow reactions indistin- guishable in color from the true urochromogen reactions oc- curred in the majority of fifty-eight normal urines. These re- actions were mostly transient and their permanency depended directly upon the amount of reagent used. Thus, in a very small number of urines, the yellow persisted beyond 30 seconds in the 5 and 3 drop tubes, and beyond 15 seconds in the 2 drop tube, while all yellow had disappeared in the 1 drop tube at 15 seconds. For this reason the time limit for transient reac- tions was established at 60 seconds for the 5 and 3 drop tubes, at 30 seconds for the 2 drop tube, and 15 seconds for the 1 drop tube. Yellow reactions persisting beyond these time limits were interpreted as positive reactions. In the two series of 94 fresh morning urines and 167 twenty-four hour specimens from pa- tients in which no red was found in the diazo solution, there was 572 LABORATORY METHODS a slight tendency for the yellow to persist in the 2 drop and 1 drop tubes beyond their respective time limits for normal urines. In fact, 1 positive reaction was found in the 2 drop tube, and 2 positive reactions were found in the 1 drop tube, while the 5 and 3 drop tubes were negative. This clearly indicated that the lesser quantities of reagent were more sensitive in demonstrat- ing very slight reactions than were the larger quantities of re- agent. In four of the above urines, showing a slight diazo reac- tion, the urochromogen was recorded negative in the % dilution of urine, in all tubes. Diluting the urine to % and'repeating the test gave distinct reactions in the 2 and 1 drop tubes, in two of the urines, and questionable reactions in the other two. All these urines were deep yellow in color. The influence of the age of the specimen on the reactions was determined by com- paring the reactions obtained on fresh normal specimens, with the reactions obtained twenty-four hours later, on the same speci- mens. The difference was insignificant, showing a slight loss in the permanency of the yellow. From these facts, the following standardization of Weisz's urochromogen test was attempted. Place 5 c.c. of % dilution of urine (1 part u. and 2 parts water) into each of two test tubes, selected so that the column of liquid is 3.5 cm. deep. Hold both tubes over a white background, which reflects the light strongly and place 0.1 c.c. potassium permanganate (1:1000) in one of them. Shake quickly and look into the tubes from above. Record any increase of yellow at the end of 30 seconds as a posi- tive reaction. If in doubt repeat the test, using only .05 c.c. of reagent and look for yellow at 15 seconds. If still in doubt use a y 5 or % dilution of urine, and repeat the test. Indican Determination. — For the determination of indican 1 have employed the reagents recommended by Robin, adding a quantitative modification which may be carried out quite ac- curately. To 20 c.c. of urine add 2 c.c. sat. sol. lead acetate. Filter. To 10 c.c. filtrate add 10 c.c. Obermayer's reagent. Set aside to cool about 30 minutes. Add 20 drops of chloroform. Shake 30 seconds. Let stand 2 minutes. Add potassium chlorate solu- tion (34.6 gm.:1000 H 2 0) drop by drop, shaking twice as above, INDICAN DETERMINATION 573 between drops until no blue remains in the chloroform. One soon learns to judge as to the approximate number of drops re- quired in a given specimen, so that in a chloroform extract requiring 15 drops to decolorize, nine or ten drops may be safely added at once. Five minutes should be allowed each time for the full effect of the previous drops, before new quantities of the reagent are added. To carry out the test conveniently and accurately, I have used a small bulb bottle blown from glass tubing, of about 30 c.c. n Fig. 101. — Bulb and pipette for convenience in making quantitative indican determina- tions. A, chloroform extract in bottom of bulb; B, paramne on outer wall of point of pipette. capacity, pouring the nitrate into it from a graduate and then rinsing the graduate with the Obermayer's reagent. The drops are added by means of a standardized pipette, the outer surface above the point of which is covered with paraffine. The KC10 3 thus adheres only to the end. Fifty drops equals exactly 1 c.c. if dropped slowly to avoid forcing off the drop by rapid currents. With care the paraffine need not be replaced for two or three weeks, although if the drop adheres in the least to the wall above the point, it will be too large. I have tested this dropping method day after day for two weeks, under diverse 574 LABORATORY METHODS atmospheric conditions and have found that the variation was less than 1 drop from 50 drops to the c.c. (See Fig. 101.) The result of a given test is expressed in the number of c.c. of KC10 3 which it would take to decolorize the total twenty- four hour quantity of indican by the following formula. Number of drop X 10 X Number of hundreds of urine. 50 Thus, if in a urine of 1500 c.c. it takes 6 drops to decolorize the indican in 10 c.c. of nitrate, the application of the formula would be 6x10x15 = 18. 50 The average elimination of indican in twenty-seven normal persons on a mixed diet was found to be fifteen by this method. The color and clearness or cloudiness of the chloroform extract should be noted. In normal persons the bleached extract ranges from no color at all to light shades of brown, or yellow or mix- tures of both, and is perfectly clear. With stomach and bowel disturbances the extract gives deeper shades usually with the addition of red, though sometimes dull green shades are found. The extract is cloudy in the majority of such specimens. The other tests mentioned, require little notice as they are well known. In employing Fehling's solution for reducing bodies, I have been accustomed to indicate the slight degree of reduction by substances other than glucose. The degree of re- duction is indicated by the sign + meaning a blue green, + + a pure green, and + + + a yellow or colorless reaction. These re- actions are recorded at the end of two minutes. Tubercle Bacilli in Urine. — Cases of tuberculosis of the kid- ney or bladder rarely come to us; so that no effort has been made to study the urine for tubercle bacilli, except where pus is present. I invariably examine for bacilli in such cases. The technic employed is the use of the mechanical shaker followed by the addition of .25 per cent sodium hydrate according to the Ellermann and Erlandsen technic, if concentration is desired. The bunching of bacilli in urine is extreme as compared with the findings in sputum. I have made differential counts of free TUBERCLE BACILLI IN URINE 575 bacilli and bunches in eleven different specimens from as many patients. The largest ratio of total bacilli to the number of free bacilli and individual bunches was 11.904; that is, with complete resolution of bunches and homogenization, the chance of finding the first bacillus in a given period of time would be increased 1090.4 per cent. The average ratio of the 11 specimens was 3.597, showing a much greater tendency to bunching than is ob- served in bacilli in sputum (see Tables VI and VII). In one case I had an opportunity to compare the ratios found in the urine specimen and in caseous material from the kidney after nephrectomy. The ratios from urine and kidney were respec- tively 2.833 and 2.718. The cavity containing this material did not communicate with the pelvis of the kidney. From these observations, it might be suggested that for diag- nostic purposes, such technic is indicated as secures resolution of bunches and thorough homogenization. This is found in the mechanical shaker after 5 per cent xylol or ligroin has been added to the specimen. In one specimen in which 5 per cent xylol was added and shaken 20 minutes almost perfect resolu- tion was attained. The direct smear gave a differential of 1000 free bacilli to 4223 in bunches; shaking with xylol gave 1000 free bacilli to 58 in bunches. On the other hand, the bunching is so characteristic of tubercle bacilli, that one wonders if it is not sufficient in itself to determine a positive diagnosis, and therefore should not be disturbed. Smegma bacilli, in my ex- perience, do not show this arrangement. Because of my limited experience in these cases, I hesitate to recommend the xylol or ligroin method even though their efficiency in resolution is almost perfect. BLOOD. Although a large amount of work has been reported dealing with blood counts, hemoglobin estimation, differential counts, etc., the opinion is more or less prevalent that the results ob- tained do not justify the time required to make such observa- tions, at least as a routine procedure. While agreeing with this view in a general way, I have, nevertheless, made these deter- minations as often as time would permit, hoping that we might be able to place a better interpretation upon them. 576 LABORATORY METHODS Practically all of my counts have been made within thirty minutes prior to the midday meal. The white cell count made at this time is from one-third to one-fourth greater than after the night's rest before the patient has stirred about. The technic is the usual one, though instead of using a steel lancet, the edges of which are always rough, at least microscopi- cally, a capillary glass tube is used, the end of which is sharp- ened into an angular point by inserting a small pointed instru- ment and prying first to one side and then to the other. The glass broken off leaves a lance point which is sharp and the edge is microscopically smooth. One can make a variety of cutting edges, — broad, narrow, long or short, and select the one which the conditions of the skin and the appearance of the surface circulation suggest. This method of puncture is far less painful than the old method, and the objectionable pressure on the part is no more necessary than with the usual method. As the hemoglobin and red cell counts in the blood of the tuberculous give the picture of a simple anemia, I have not made the red cell count unless the anemia was severe. The hemoglobin is determined by the Sahli instrument. The white cell count, the general differential, Arneth's differential, and certain toxic changes in the neutrophiles, have been considered of most importance. General Differential. — For the purpose of making differential counts No. 1 cover slips are used. In well made smears one may always study the error in distribution, while, with the slide method, there is an unknown amount of displacement of the larger cells, mainly transitionals, to the edge. There is some displacement with cover slips, but as the films are much more uniform in thickness than can be obtained by the slide method, the error can be corrected. The first hundred cells counted at the thick edge often give 10 to 15 per cent of transitionals, while the first hundred cells counted at the apex of the film gives from to 5 per cent. So, in counting, I invariably select the middle third, avoiding both extremes. Hasting 's and Giemsa's stains are used, preferably the former. Five hundred cells are always counted, classified as neutrophiles, basophiles, eosino- philes, large mononuclear, transitional and stimulation cells. arneth's index 577 Arneth's Classification of Neutrophils. — There is considerable difficulty in making smears suitable for Arneth's classification. Even in the best of films where there are from one to three thou- sand leucocytes suitable for a general differential count, one may, with difficulty, find three hundred neutrophiles satisfac- tory for Arneth's classification. Only the thin portions of the film may be counted lying between the center, where the cells are more or less crushed, and the outer thicker margin. The cells must be spread sufficiently so that the lobes of the nuclei may be readily recognized. However, in the best of films, there are 10 to 15 per cent of neutrophiles that defy accurate classifica- tion. I always rely on the number of connecting threads in case the lobes of the nuclei overlap, since there is always one thread less than there are lobes. I have not obtained as low indices on normal persons, as have been reported by some ob- servers. I am inclined to believe that in some of these reports nuclear buds have been mistaken for lobes, and thus the index is lower than it should be. These buds are common in neutro- philes from the blood of the tuberculous as well as from the blood of apparently normal persons. They are connected with the parent lobes by threads indistinguishable from the threads connecting the lobes themselves, except that they spring from the side of the lobes, never from the ends, or long axis. I have counted as high as 25 of these buds in 100 neutrophiles, which would greatly lower the index, in case they were mistaken for lobes. Giemsa's stain is somewhat superior to Hasting 's for Arneth's counts, but as it is less suitable for general differential counts, I have not used it to as great an extent. My average normal indices, as computed by the method of Bushnell and Treuholz is 57; that is, the sum of Classes I and II, plus y 2 of Class III. Nuclear and Protoplasmic Changes in the Neutrophile. — Years ago Holmes observed certain changes in the neutrophile of the tuberculous patient. My observations confirm in part, what he described, but there are some characteristics which ap- pear of especial importance. These changes are always asso- ciated with a toxic condition, manifested by temperature and other signs of an active process. They consist in the appearance of small granular bodies in the protoplasm, approaching black 578 LABORATORY METHODS in color. The prominence of these granules is designated by the signs |+, +, + +, and + + +, the first indicating very slight, and the last an extreme change, where the granules are large. The latter is invariably found in patients just before death. Coincident with this, the pink tone of the neutrophile tends to disappear, and the protoplasm approaches the basophilic type. I cannot say whether these dark, almost black granules are peculiar to tuberculosis, as I have not had sufficient experience in studying bloods in non-tuberculous infections. But records have been made of certain differences met with, in a case of appendicitis, one of typhoid fever, and a case of pernicious anemia. In none of these would the granules be confused with those present in the toxemia of tuberculosis. The case of ap- pendicitis later came to operation and a simple catarrhal con- dition was found. The case of typhoid ran the usual course. This protoplasmic transformation or stippling, is never present with a normal Arneth count. But a marked Arneth change may occur without the protoplasmic change. As young cells always show greater affinity for aniline dyes than do the adult cells, some change would be expected in neutrophiles from patients with a high Arneth index, where the young cells are increased in the circulation. The stippling is always associated with a considerable degree of toxemia, with more or less constitutional symptoms, while a high Arneth index may be found in cases without such symptoms. FECES. Aside from the search for tubercle bacilli, the examination of the feces from tuberculous patients gives little or no informa- tion peculiar to the disease; consequently, routine examinations have not been made except where indicated by symptoms point- ing to bowel complications. Tubercle Bacilli. — In examining for tubercle bacilli, visible particles of mucus, if present, are homogenized, as in making direct smears of fresh sputum. In case none are found the speci- men, after grinding in a mortar, is diluted with two parts dis- tilled water, transferred to a bottle and shaken in the mechani- cal shaker. After allowing the coarse undigested particles to TUBERCLE BACILLI IN FECES 579 settle, a smear is made from the upper more finely suspended material. The preparation of the smear and staining are car- ried out as described under sputum, except that absolute alcohol is substituted for 70 per cent alcohol in decolorizing. In 1907 and 1908 a study was made to determine what value the routine examination of feces would be to the clinician. The technic employed was as described above. The time of search, however, at that time, had not been standardized, for either sputum or feces, so only a guess may be ventured that it was 5 to 10 minutes. In order to exclude bacilli from the lung as far as possible, the patient on entrance was cautioned about swallowing his sputum, and 5 days were allowed for previously swallowed bacilli to pass from the bowel. At the end of this time the specimen was taken. Two hundred and sixty-nine specimens were examined from 146 patients. Bacilli were present 107 times and absent 40 times in the feces of 68 patients with bacilli in the sputum, and they were present 4 times and absent 118 times in 78 patients without bacilli in the sputum. Two types of other acid-fast organism were occasionally found, — one rather short, very deeply stained, and broader than the tubercle bacillus; the other very pale, and of rather close relationship morphologically to the tubercle bacillus. The first type would not be likely to confuse one who is familiar with the tubercle bacillus in sputum. The latter were distinguished by their uniformly weak acid-fast property; and I did not consider them tubercle bacilli. My later experience justifies this con- clusion. On the whole, I do not consider that the differentia- tion of tubercle bacilli from other acid-fast organisms met with in the feces presents any very difficult problem, if care be taken to secure uniform penetration of stain. This point has been discussed under sputum. The presence of tubercle bacilli in the feces seldom points to tuberculosis of the bowels, at least clinically. It is highly improbable that patients can guard against swallowing some of their sputum. As shown in the work above, in which bacilli were recovered in 73 per cent of all specimens from patients who showed bacilli in the sputum, only three of these patients gave evidence of intestinal tuberculosis. 580 LABORATORY METHODS It is sometimes strongly advocated to examine the feces from all suspected cases where sputum cannot be obtained. The four diagnoses made from examination of feces in my series appar- ently confirm this view, since in two of the four cases bacilli were later found in the sputum. But had the same care been taken in the collection of sputum at that time as is taken now, it is probable that those diagnoses would have been made from the sputum. In fact, since that time I have not found bacilli in the feces in a single instance, in which they were not also pres- ent in the sputum. There have been three instances within the past five years, in which patients with clinically active lesions insisted that they had no sputum on first examination; but at succeeding examina- tions plenty of sputum with bacilli, was obtained. One of the three intentionally deceived us and the other two had not been properly instructed. Examination of feces in these cases might have given positive results. On the whole, however, the routine examination of feces for diagnostic purposes will be found a time-consuming procedure and a very poor substitute for thor- ough sputum examination. It is sometimes necessary to examine the feces for occult blood. I have used the aloin and guaiac tests for this purpose. The feces are ground in a mortar; a small portion (1-2 gm.) is placed in a test tube and 1 c.c. of glacial acetic acid added and shaken; from 3 to 5 c.c. of ether are now added and shaken. A portion of the ethereal extract is transferred to a small test tube and a small quantity of freshly powered guaiac gum is added and shaken; five drops of old turpentine (made by ex- posing chemically pure turpentine to the air for several weeks) are now added. In the presence of blood a blue to tokay color develops at the point of contact of turpentine and extract; or by shaking, the whole of the turpentine takes on the color. The aloin test is made by adding old turpentine to a portion of the ethereal extract, and then 6 to 10 drops of an alcoholic solution of powdered aloin (a pinch of aloin in ^ to 1 c.c. of 70 per cent alcohol). The development of a bright red color within 5 minutes time at the line of contact of turpentine with the solution indicates the presence of blood. Beyond this time INTERPRETATION OP LABORATORY FINDINGS 581 limit the aloin-extract mixture tends to change to red even though blood is not present. Patients must be kept off a meat diet for three days previous to the collection of the feces; otherwise either test may react positively to the blood contained in the meat. INTERPRETATION OF LABORATORY FINDINGS. For purposes of diagnosis and especially prognosis, the inter- pretation of laboratory findings in pulmonary tuberculosis pre- sents a difficult problem. Various tests have been brought forth with startling claims, only to be discarded entirely or to be relegated to the position of a link in the chain of evidence upon which the judgment of the clinician is based. Arneth's index, the albumin reaction, and the diazo have a similar history, il- lustrating the truth of the previous statement. Further, if we keep in mind the pathology and the general course of the dis- ease, it is difficult to understand why we should expect any given test to supply us with all the information desired in forming a judgment. Such opinion may be formed from a knowledge of the extent, activity, and probable duration of the disease process. The findings in blood, sputum, urine, and feces are but sec- ondary to the disease process, and are of importance only as evidence of its extent and activity at the time of observation. Only in a very general sense can this information be of prog- nostic value. Nor may it be expected that this unsatisfactory condition will be remedied until more delicate serological and chemical methods have identified the primary principles condi- tioning infection and resistance to infection. Probably this in- formation will come largely through increasing knowledge of the internal secretions, and cell ferments. Working under such limitations, we must not expect too much from the interpreta- tion of our data. The making of diagnoses a little earlier and more confidently; the more certain determination of the nature of the complications which arise in the course of the disease; the collection of data which at best is only of limited value in establishing a prognosis; the accumulation of information, which, though of little or uncertain value in treating the individual patient, may in the aggregate throw much light upon the tuber- 582 LABOKATORY METHODS culosis problem as a whole; these results are about all that may- be expected. Diagnostic and Prognostic Value of Individual Laboratory Findings. — The weight of individual findings varies somewhat with respect to whether or not bacilli have been found in the sputum; so, in the following discussion individual tests will be considered: first, as found in the prebacillary stage of the dis- ease; and second, as found with bacilli in the sputum, after cavitation has taken place. For the most part, such findings are of presumptive evidence only, as they are not wholly specific for tuberculosis. Sputum. — The nearest specific finding is a high lymphocyte content in the sputum. Fifty per cent or more of these cells indicate tuberculosis in probably over 90 per cent of cases, al- though theoretically a number of other lung conditions should give the same picture. As yet, however, nothing has been re- ported to minimize the importance of this finding as pointing to tuberculosis. The later development of bacilli in the sputum of some of these patients and the occurrence of the same picture in old healing lesions, is convincing. The albumin reaction is less reliable as it is present wherever pus is found, unless it has been previously split by the action of ferments and bacteria in the lung. Such loss of albumin is found in conditions favoring retention of sputum, such as lung abscess and some cases of bronchiectasis. Chronic bronchitis gives little or no albumin in the sputum; acute bronchitis with high pus content gives a considerable reaction. Any albumin reaction then, persisting over a period of time longer than the course of acute infections, is due probably to tuberculosis. Af- ter cavitation has occurred, the presence of albumin is constant until healing has taken place. Disappearance of Bacilli Under Treatment.— Of special im- portance to the patient and his friends is the permanent disap- pearance of bacilli from the sputum, during the course of treat- ment. The more extensive the involvement the more difficult it is to secure this result. Also, the better the technic employed in searching for bacilli, the less glittering will be the result. Rare bacilli, formerly overlooked by our cruder methods, are DISAPPEARANCE OP BACILLI 583 found today; so that the high percentage of patients positive on entrance but losing their bacilli under treatment, reported in past years, does not hold today. In 1909 a clinical report was published including all patients who had been in the sanatorium for at least 3 months. There were 277 patients who had bacilli on entrance, classified as i Stage, 12; n Stage, 26; and in Stage, 239. Of these, 11 of the i Stage, or 91 per cent; 16 of the n Stage, or 61 per cent; and 17 of the m Stage, or 7.1 per cent, lost their bacilli during treatment. The average course of treatment was 6 months for the i Stage ; 8 months for the n Stage ; and 10 months for the m Stage. The sputum examinations at that time were made mostly from morning specimens, partly after direct smear and partly after fermentation of the specimen. A small proportion of the exam- inations were made from twenty-four hour specimens followed by fermentation. The collection of twenty-four hour specimens was started in July, 1907; although in patients with bacilli, morn- ing specimens were considered sufficient. Beginning with July 17, 1911, twenty-four hour specimens were collected as a routine procedure, and the three-day specimen was adopted for all pa- tients in whose sputum bacilli had previously been negative or rare. Since that time, in a total of 5160 sputa examined, 1150 have been three-day specimens. Table XIII is a summary of all patients who were, under treatment for at least 3 months, and in whose sputum bacilli were found at least once. The patients are arranged in two groups: those leaving prior to July, 1911; and those entering after July, 1911. The number of patients in the i and n Stages above are too few in number to make valid comparisons; but in Stage in and in the total of all stages, a diminution in the percentage of patients losing their bacilli, during the course of treatment, is noticed when the better technic is used. The percentage is re- duced from 8.4 per cent to 4.7 per cent for Stage in cases, and from 10.7 per cent to 8.5 per cent for all stages. The percentage of those negative on first examination but developing bacilli during the course of treatment is slightly less with the better technic, due probably to greater effort in making the first ex- amination successful. While the percentage of patients who 584 LABORATORY METHODS TABLE XIII. Showing Reduction of the Percentage of Patients Losing Their Bacilli Under Treatment, When Better Technics are Employed Examinations before July 17th, 1911. Technic employed. Fresh morning specimens and 24 hr. specimens exam- ined by direct smear and after fermen- tation. Preparations searched for 5 to 10 min. before reporting negative. After July 17th, 1911 Technic employed. All specimens were 24 hr. or 3 day quantities, fermented and shaken in the mechanical shaker. Preparations searched for 15 min. before reporting negative. TOTALS I STAGE II STAGE III 1 STAGE ALL STAGES TOTALS I STAGE II STAGE III STAGE ALL STAGES Patients 6 19 274 299 Patients 7 34 254 .295 Examina- tions 43 91 2414 2558 Examina- tions 59 157 2522 2738 Average ex. per patient. . . 7.2 4.6 8.9 8.6 Average ex. per patient. . . 8.4 4.6 10 9.3 Patients losing bacilli 3 6 23 32 Patients losing bacilli 4 9 12 25 Loss per cent. . 50 31.6 8.4 10.7 Loss per cent. . 57.1 26.5 4.7 8.5 Patients gaining bacilli. . . . 3 10 13 Patients gaining bacilli. . . . 2 9 11 Gain per cent. . 15.9 3.7 4.3 Gain per cent. . 2.9 3.5 8.7 lose their bacilli has been considerably reduced, the percentage of favorable clinical results has been increased. From these facts it is evident that the chances for a patient in Stage in getting rid of his bacilli during the average period of treatment — 9 months in the above series — is very small; and if still more sensitive technics were employed — pig inoculation or Petroff's cultural method — the chances would approximate zero. These cases must then be considered as possible carriers for a long period of time after treatment. Another feature in the comparison of the two technics which does not appear in the table, is the higher percentage of patients who show bacilli intermittently by the better than by the poorer technic. There were eighty-four intermittent cases INTERPRETATION OF BLOOD FINDINGS 585 in a total of 295, or 29 per cent in the former; and 69 in a total of 299, or 23 per cent in the latter. Blood. — Blood findings offer little aid to diagnosis in the pre- bacillary stage, except in comparatively rare instances where cavitation is preceded by severe constitutional symptoms; in such cases the almost specific character of the neutrophile stip- pling has enabled me to differentiate between tuberculosis and certain other non-tuberculous conditions. Rarely one meets a case of miliary tuberculosis presenting the same picture clini- cally; the presence of a leucocyte count below 5000 speaks for the miliary condition with a grave prognosis; a high leucocyte count — 10,000 or above, depending on the severity of symptoms, rather indicates approaching cavitation, without prognostic sig- nificance. Arneth's variation in the neutrophiles is entirely non- specific, occurring in practically all infections with constitutional symptoms, A high lymphocyte count was formerly looked upon as of diagnostic value, but so many other conditions produce the same picture that little may be expected of it; further, the discovery in later years that the average lymphocyte percentage in normal persons is much higher than was originally claimed by Ehrlich has also discounted the value of the lymphocyte per- centage. After cavitation has taken place, however, there is a close parallel between the number of lymphocytes in the blood and the general welfare of the patient. The higher the count, the better on the average is the condition of the patient, and vice versa. For prognostic purposes a count of 500 or below indi- cates an almost certain fatal issue. Urine. — The urine findings before bacilli appear in the sputum are of little value. The occurrence of a diazo and urochromogen are rare, and when they are present they are associated with the severe constitutional symptoms accompanying extensive soften- ing or a miliary condition. These two conditions might at times be confused with typhoid fever accompanied by pulmonary and pleuritic symptoms. As the diazo is likely to occur in all these conditions, it is of no value in differentiating, but it is of some value in excluding pneumonia in which it occurs less commonly. The diazo is not frequent in tuberculous meningitis unless the condition is terminal to massive pulmonary involvement, so that 586 LABORATORY METHODS it should be of some weight in differentiating tuberculous menin- gitis from typhoid fever, miliary tuberculosis and massive pul- monary involvement, when mental confusion is present. The diazo is of limited prognostic value. An occasional oc- currence indicates nothing more than that the disease is quite active at the time of examination. Continued occurrence of the reaction gives a grave prognosis. Two patients in whom I found a positive test at y 5 dilution of the urine, during cavitation, never gave a diazo thereafter, and obtained complete arrestment. Both are alive and well, one after 6 years, the other after 2 years; on the other hand, a diazo of such intensity persisting for one month is almost certainly fatal within a few months' time. Indican findings, considered alone, are of uncertain value in the individual case, although an increased indican elimination has long been known to accompany tuberculosis. There is con- siderable variation in the amount of indican eliminated in twenty- four hours, so that little information is likely to be obtained from a single examination. Some years ago I determined the amount of indican in three successive daily twenty-four hour urines from 45 different patients. Comparing the results for the three days it was found that in 6 patients the highest reading was less than 25 per cent greater than the lowest; in 3, 33% per cent; in 11, 50 per cent; in 16, 100 per cent, and in 9 more than 100 per cent. In interpreting indican findings, one must know whether or not a cathartic was given before or during the time the specimen was being saved; and also as to the result of the cathartic. Should one find a persistent increase of indican in a patient with bowel symptoms, tuberculous enteritis should be thought of; these patients almost invariably have indican values above 30 (15 being normal; see Indican determination, p. 574) even though on a restricted proteid diet. The chief value of indican determinations has been as an aid in the regulation of the diet of the institution as a whole, as well as the diet of individual patients. In 1908, a study was made of indican reports made up to that time; the first examina- tion on entrance was compared with the average of all succeed- ing examinations from each patient. It was found that the aver- INTERPRETATION OF INDICAN FINDINGS 587 age increase of indiean in 69 patients was from 15 to 26, while the average decrease in 32 patients was from 26 to 14. The pa- tients were then classified with reference to their general condi- tion and habits of eating. It was found that those whose indiean increased markedly on our diet were almost invariably the ambula- tory patients who were trying to carry out faithfully the er- roneous teaching of "stuffing." The practice had been discarded several years before in the institution, but it could hardly be expected to die quickly after having been advanced and main- tained with such insistence by the profession. In many cases patients were told by the physician referring them that what they needed was good, nutritious food in excess of what their appetites called for. It was not an easy task to break up a habit which had such a strong reason for its existence. How- ever, the high indicanuria in at least two-thirds of the patients was so clearly dependent upon the excess of proteid food in- gested, that effort was made to break up the habit. After a course of general lectures, with a careful watch over individual cases, the indiean determinations were compared as above from the next 76 patients entering, with the result that only 23 pa- tients showed an increase of from 22.1 to 27.4, while 53 showed a decrease of 27.3 to 14.0. These averages are made occasionally, whenever there is reason to believe that the patients have for- gotten the previous lesson. The following chart shows a curve made from the averages of all indiean values found for each month for seven years. The technic has been uniform throughout. From 60 to 80 examina- tions are averaged each month, so that the chart represents the findings in about 5500 twenty-four hour urines. (See Fig. 102.) On an average the curves show a lower indiean elimination since 1912. It was before that time that we experienced most of our trouble from overeating. Aside from this tendency, there are certain other causes tending to influence the indiean curve. In April, 1912, a sharp rise in the curve followed a period of warm days entirely out of season. The remaining months of the year were cool. After a cool spring and summer in 1916, a period of two weeks of warm weather were experienced in 588 LABORATORY METHODS August, with a rise in the curve. This rise in the indican curve, with the usual train of minor symptoms, is the same condition met in the eastern states with the approach of the warmer spring months. With us it is likely to occur at any time, due to our lack of well denned seasons. Just what atmospheric conditions are responsible for this rise in the curve is not clear. It is not the temperature alone; for low indican values are often found in hot weather. It may be due largely to the effect which cer- tain atmospheric conditions have in increasing bacterial activity, rendering food less digestible, disturbing the digestion of the patients and increasing intestinal intoxication. Jak. fes. Ma*. A™. M f Y. ^ NE, «L Lr Av<*, §1 VT, Oct. Nov, Dec wo: mi. mil ml 1114, \v£ W,b n Fig. 102. — Institutional indican curve determined from the average of all indican findings for the month. Whatever the exact explanation, the curve is of much value in guiding our patients through these periods of disturbance. They are advised to diminish the proteid content of their diet. Tubercle bacilli in urine, whether from the kidney or else- where in the urinary tract, give a grave prognosis; although cases have been reported as having healed. Bacilli have been reported as having been found in the urine in miliary tuber- culosis, without involvement of the urinary tract; but as such cases are rare, confusion is not likely to result. The presence of pus with bacilli in the urine justifies the opinion that tuber- culosis exists somewhere in the tract. CORRELATION OF LABORATORY FINDINGS 589 Feces. — The diagnosis of tuberculosis of the bowel from the presence of tubercle bacilli alone in the feces should not be made; even though they are continuously present. In case bowel symptoms are present, the condition should be thought of; but the diagnosis can by no means be established for a certainty. The continuous presence of occult blood in a patient with ad- vanced pulmonary tuberculosis, provided ulcer of stomach or duodenum can be excluded, rather points strongly to tubercu- lous enteritis, if clinical symptoms are also present. This com- plication is rarely recognized until the disease is far advanced. Correlation of Laboratory Findings. — In the proper correla- tion of findings from all sources, is to be found the chief value of laboratory work; in such a method negative findings by in- dividual tests are often as important as are the positive findings obtained by other tests; the varying pathological condition of the patient causes a corresponding change in the laboratory findings; so that negative findings often enable the clinician to exclude certain disease processes from consideration in diagno- sis, while positive findings give him an idea of the nature and extent of the condition itself. When the constitutional symptoms are slight, the laboratory findings vary little from normal; but when they are pronounced, whether bacilli appear in the sputum or not, we must differ- entiate between tuberculosis and other respiratory infections. Even though we are positive that the clinical picture is one of uncomplicated tuberculosis, the assembling of the laboratory facts gives a more accurate idea of the condition of the pa- tient. In the sanatorium it is rarely necessary to differentiate tuberculosis from the acute respiratory infections on entrance; as 95 per cent of all entrants have been under the care of their physicians for sufficient time to exclude almost entirely the lat- ter diseases. The following case was an exception to this rule, as the patient was delirious and his family were unable to give a satisfactory history; they rather attributed his mental state to business worries. On entrance the patient was delirious; temperature 104.4, pulse 124. Physical examination in recumbent position was un- satisfactory, giving weak breath sounds over right apex. 590 LABORATORY METHODS Sputum: small amount; purulent in character; no bacilli pres- ent. Urine: 24 hr. 1000 c.c; albumin, large trace; diazo at % dilution. Blood: white cells 4780; neutrophiles 74 per cent; lymphocytes 24 per cent; neutrophile stippling, moderate. It was observed at the time that the stippling was unlike what I had found in severe toxemias in uncomplicated tuberculosis and a note was made of the differences. The granules were neither as distinct nor as black in color, as is invariably found in the latter. Bacilli were not present in the feces. The clinical picture presents these possibilities: tuberculous meningitis; miliary tuberculosis; massive pulmonary tubercu- losis; some acute respiratory infection, as pneumonia or influenza; typhoid fever with pulmonary complication; and finally, any of the infectious diseases with pulmonary complications in a per- son who was previously mentally deranged. The marked diazo reaction with leucopenia almost certainly limits the possibilities to miliary tuberculosis, massive pulmonary tuberculosis, and ty- phoid fever; but the physical examination, though unsatisfactory, almost certainly excluded pulmonary tuberculosis of such de- gree as would be necessary to produce such toxemia. The dif- ferentiation of miliary tuberculosis and typhoid fever was made in favor of the latter, on the character of the neutrophile stip- pling, as not due to the toxemia of tuberculosis. Two days later rose spots appeared on the abdomen. Repetition of the labora- tory tests 5 days later gave a diazo at only % dilution; white cells 4050, bacilli negative. The blood culture for typhoid bacilli was not made. Sputum and urine were examined later 3 different times, with the result that bacilli were never found and the diazo was absent at the end of three weeks. The sub- sequent history showed that we were dealing with typhoid fever. The temperature remained between 104° and 105° for 13 days, coming gradually to normal on the 21st day, and remaining normal thereafter for four weeks, except for an occasional rise to 100°. In this case the most specific finding was the character of the neutrophile stippling, which is suggested for the use of those workers who have more opportunity for differentiating these cases than I have had. In the following case, I believe the laboratory findings were CORRELATION OF LABORATORY FINDINGS 591 important not only in confirming the physical findings, but in indicating a more accurate prognosis than would be ventured from the former. There was no question of the diagnosis of tuberculosis, although bacilli had never been found. The patient gave a history of cough at times with or without sputum. Six weeks before entering the institution he had a "cold" lasting for three weeks, with a maximum temperature of 102° to 104°, and subnormal in the morning. Physical examination showed extensive infiltration in both lungs. The temperature on en- trance was 99°; pulse 90. Sputum, 24 hour specimen, gave no bacilli. Urine, no diazo. Blood, white cells, 3850. Because of the leucopenia, the white cell count was repeated the next day, giving 3900. Three days later it was 5700; lymphocytes 910; Arneth's index 97. Three days later, the count was 3500; a diazo at V2 dilution was found in the urine; and a 3 day sputum was negative for bacilli. At this point the temperature was 102° without morning remission, continuing in this manner until death 10 weeks later. Laboratory examinations were repeated 8 days after the last examinations. The white cell count was 4050; diazo %; tubercle bacilli 25 per field. The white cell count repeated 10 days later was 4700, and 8 days after that, 6050. Seven weeks after entrance the urine gave a diazo of y 12 ; the sputum 75 bacilli per field. The main point of interest in this case is the persistent leuco- penia, associated with the increasing intensity of the diazo, which justified the opinion of an early fatal issue, which was not in- dicated by the history and physical findings. The second com- plete physical examination, made one month after entrance, showed that areas of infiltration had increased markedly. This was a case of miliary tuberculosis of the lung. Since developing the special technics for the determina- tion of the sediment volume and the length index of tubercle bacilli, I have found the findings very valuable in explaining the nature of the lesser changes taking place in the patient's condition from day to day. Those who are engaged in following the course of the disease in tuberculous individuals, know of the vast number of little complaints of such patients, such as V2 to 1 degree rise in temperature without evident cause; the 592 LABORATORY METHODS tendency to tire easier on certain days as compared with others; loss of appetite, etc. These complaints come from those who are comparatively well, as well as from those who have considerable involvement with constitutional symptoms. There has been some speculation concerning the meaning to be attached to the relative length of bacilli found in sputum; the two important opinions being: first, that the short uniformly stained forms are of the bovine type, while the long and beaded forms are of the human type; and second, that the short and long forms are the younger and older bacilli respectively. Al- though I have kept routine records of the estimated relative length of bacilli for eight years, I came to the conclusion that it was practically impossible to form an idea of the relative length of bacilli, without some scheme for measurement. Since perfecting such a device, I have been able to classify bacilli to within a narrow margin of error. I find that many of the com- plaints referred to above are associated with the softening of minute areas in the lung, as is shown by the increase of the short bacilli. We have in this method a means of detecting these slight changes, which neither the stethoscope nor other means, of which I know, can determine. Such information is of great value in individual cases, such as those showing very irregu- lar temperature curve, and in which there is doubt as to whether the temperature is referable to the lung involvement, to some tuberculous complication, or to some non-tuberculous process. To rely on the patient's statement that he is coughing and raising more today than he did yesterday or last week often leads the clinician to wrong conclusions. Changes in atmospheric conditions may produce those symptoms, and may even produce a slight rise in temperature. Further, worry, fright, anger or other emotion may either directly or indirectly affect the tem- perature curve, producing a train of symptoms besides the ones mentioned. The differential diagnosis in these cases has re- peatedly been made to the satisfaction of the clinicians and the patient himself by means of the sputum findings as illustrated in the charts. (See Figs. 103 and 104.) In addition to the temperature curve the charts present 5 curves made from quantitative observations extending over sev- CORRELATION OP LABORATORY FINDINGS 593 eral months. The temperature curve was made from the aver- ages of the highest temperature for the day, of three successive days. This method minimizes the influence which various out- side factors would have on the curve. For instance, indigestion Total Alb. ~nov. Dec Jati Feb. IS "mo.r. A?T\ 3 3 2 Jul. Aug. Sef. 7 ISO faooo T / fc>0 i"000 ,,'' \ 1^0 z/ooo '-..^ ^'' |Z/0 3ooo / \ \ (00 JjOOO t y \ \ V «0 iOOQ / zv V \^ 60 A ----" " y y \ \ *• W Bic 2/0 «0 fco B / \ 40 / s • \ Index ao ^ "*- ■ s \ N (fco ^ ^ --— ' \ ISO D \Ho Sed. IbO 10 '^*^^ ^< IZO 8 s — -_ ^~~~~ " 6 s — _ / ' s V S / \ 1 / "**-<, £_ — -"-" Temv. lot? 10 1° 100° Tneti* tUAt 071 ♦ ♦ ♦ ♦ ♦ ♦ ♦ + Fig. 103. — Chart showing correlation of sputum findings and their relation to tem- perature curve. A, Albumin curve; B, total 24 hour sputum; C, number of bacilli; D, length index; E, sediment volume. and the various emotions, may cause a rise for a single day of one or two degrees, but when averaged with two days of usual temperature, it would not appear of much importance on the chart. Fig. 103 presents the findings in a female patient whose 594 DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS lung involvement has extended under treatment. It will be noticed that in general the albumin, total quantity of sputum, relative number of bacilli, and sediment curves are in agreement with the temperature curve. The length index curve bears an inverse relation to the other curves; that is the greater the activ- ity the shorter the bacilli, and the lower the index. This rela- TolQl Alb. Cu.5. StH Oc X Tlou. S&o Jan. J IfeO WfiO A / ^ 1^/0 / \\ I&0 *fco / \ \ _„."" 100 A ' y \ So a y \ fco 8o.o. ~^ — ' ■ to Zoo lo too / ^00 / s -- InAtt ?00 / "\ irfo ~""-* 2-00 &tl iqo 1>S D ^y V (So to \ l7o is £ -""^ IO \ ^'*^ S Tern? t _ . 1 _4 n °i • 'rwvww ym Fig. 104. — Chart showing correlation of sputum findings and their relation to tem- perature curve. A. Albumin curve; B. total 24 hour sputum; C, number of bacilli; D, length index; E, sediment volume. tionship is shown in Fig. 104 and in some 40 other charts, which I have made from other patients, establishing beyond all doubt the meaning of short bacilli, and confirming the opinion of others who have expressed this view. This view does not necessarily weigh against the other opinion that short bacilli represent one type and long bacilli another type. The greatest fluctuation in CORRELATION OF LABORATORY FINDINGS 595 index which I have met in any single patient was from 264 on entrance to 204 after cavitation two months later. Another patient on entrance gave an index of 177, and after two months of unusual progress, an index of 218 was found. Some of these patients have been under observation for 10 to 15 months, and while the index varies considerably, it does so within fairly narrow limits — 50 to 40 points in index — which is not great considering the possible range from 127 to 264 as found in my work. This rather points strongly to a number of different types of organisms. I have not been able to find any special significance in the al- bumin curve, and the total 24 hour specimen varies so greatly that its curve is of little value in studying these finer points in diagnosis; so that in practice, the sediment volume, length index, and relative number of bacilli are given most weight. CHAPTER XXI. TEE DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS OF TUBERCULOSIS, PARTICULARLY PULMONARY TUBERCULOSIS. The diagnosis of tuberculosis is so intimately associated with, its differentiation from other conditions that it seems logical and best to discuss these subjects together. The Importance of Diagnosis in Hidden Tuberculosis. — AVhile our chief duty as clinicians, as yet, so far as tuberculosis is con- cerned, is to diagnose the disease as it affects the lungs, yet we must not lose sight of the fact that it may affect any tissue or organ of the body; and that each lesion may produce the same group of toxic symptoms together with a group which will be characteristic of the particular tissue or organ affected. It is especially necessary to bear this in mind if we would understand the indefinite group of toxic symptoms which accompany a partially quiescent focus in the peribronchial or tracheal glands where the main complaint of the patient is that which might be caused by any slight toxemia. In such cases we have the picture of loss of tone and lack of nervous and physical force without any apparent cause. In malarial districts malaria is usually diagnosed, while, in other places neurasthenia, overwork, or a general rundown condition is supposed to be the cause. As clinicians we are apt to forget the possibility of such symp- toms being caused by hidden foci; and, failing to find tubercu- losis in the lung, declare that it does not exist. We should never lose sight of the fact that, with clinical symptoms belonging to the toxic group suspicious of tuberculosis, and an inability, by most painstaking examination, to find either a tuberculosis or other cause for the same, we have not ruled out the possibility of a hidden tuberculous focus. The pulmonary tissue is not the only part attacked by this infection; in fact, the peribronchial and peritracheal glands are nearly always infected prior to the DIFFICULTIES OF DIAGNOSIS 597 pulmonary involvement and symptoms can arise from the escape of toxins from these glandular foci, even although the glands may not be enlarged sufficiently to cause symptoms other than those of a toxic nature, and even though they cannot be out- lined on physical examination. It is equally important to remem- ber that, given a lesion in some organ other than the lung which is suspected of being tuberculous, with undeniable evi- dence of tuberculosis being present in the body of the patient, such as a positive tuberculin reaction; or, a positive sputum finding, this positive evidence does not prove the tuberculous etiology of the process in question. Difficulties of Diagnosis. — The difficulties which attend the diagnosis of tuberculosis come from many sides. The fact that tuberculosis has been a fatal disease for so many centuries still militates against its detection. Although tuberculosis if diag- nosed early and treated intelligently has been removed from the list of fatal diseases, yet this is only accepted in a half- hearted manner. It is not fully believed by either the lay- men or the profession. This lack of faith in its curability adds to its deadliness because it keeps up such a fear of the disease that the patient and his friends fight against knowing the truth, and medical men shrink from finding it out, or, if they know it, from telling the patient until the early curable disease has be- come an advanced hopeless one. This can only be remedied by medical men accepting what intelligent treatment can do for truly early tuberculosis and appreciating the great danger of delay; and then proclaiming it far and wide until the truth is fully known. It requires Herculean effort to work against the tide of uni- versal public opinion; yet, this is the task imposed upon those who are striving for early diagnosis and cure of tuberculosis. The insidiousness of tuberculosis is also a factor which makes the real diagnosis difficult. If symptoms came on at once after infection took place, it would be comparatively an easy matter to make an early diagnosis, but such is not the case. Infection in tuberculosis takes place weeks, months, or years before clini- cal symptoms are recognized, the lesion having gone through a succession of changes from quiescence to activity and extension. 598 DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS This goes on until the process is sufficiently extensive or un- til the activity is sufficiently great to produce symptoms which are unmistakable. It is not the frank, unmistakable symptoms which we should look for. These are evidence of advanced dis- ease. We should always, bearing in mind the frequency and in- sidiousness of this disease, be on the alert and learn to recognize the earliest symptoms which occur. If only there was some group of symptoms which is pathog- nomonic or some specific tests which are infallible in their diag- nosis of early tuberculosis the problem could be minimized. But there is not; so we are often obliged to make a diagnosis by exclusion rather than by positive data. The symptoms of early tuberculosis differ according to the nature and location of the lesion. Toxins produce many of them; but the lesion must be of some extent before these are present in sufficient amount to be evident; and in some loca- tions the symptoms caused by the inflammatory process are more marked. In such locations as the meninges, bones, joints and pleura, symptoms dependent upon toxemia are comparatively unimportant at first; so are they often in glandular tubercu- losis, and even in the early pulmonary form. On the other hand, if the disease is located in the tissues where it can run a chronic course, sooner or later the toxic group of symptoms be- comes important. In marked glandular tuberculosis and in pul- monary tuberculosis, beginning with the so-called early lesions, which are in reality lesions which are more or less extensive, toxemia is usually accountable for a definite group of symptoms which must be considered in the diagnosis; but, unfortunately, these are not constant. In genuinely early lesions there is no definite known blood picture; there are no secretions to analyze; and the specific re- action of the body cells and tissues to the products made from the tubercle bacillus (tuberculin) is usually, though I believe wrongly, considered as being of no value except in the first few years of life. The x-ray can give evidence, which, if rightly interpreted, may be of value in early infections located in some tissues, particularly the joints and bones, and at times plates made by the best apparatus with expert operators will greatly DIAGNOSTIC IMPORTANCE OP TUBERCULIN TESTS 599 aid in the diagnosis of lesions in early pulmonary invasions. The Importance of the Tuberculin Tests in Diagnosis.— The function of the tuberculin tests in diagnosis is not understood because there are so many things about the specific reaction be- tween tuberculin and the sensitized body cells that we do not know. However, it is true that we are arriving at some definite opinions. Our judgment of them, now that we know the fre- quency of tuberculosis in early years and understand its tend- ency to go through cycles of activity and quiescence over a long period of time until it either heals or produces frank clinical tuberculosis, should help us in at least having respect for a reaction when found, even if it does not afford us the help that we desire at the time. What clinician can say, by the most careful minute examina- tion that a hidden focus of tuberculosis is not present in some portion of the patient's anatomy? Yet it is an every day oc- currence for physicians to make such statements and put up such opinions against positive tnberculin reactions. They do not presume to do so in syphilis. If a positive Wassermann is found, the clinician accepts the diagnosis whether he is able to find a trace of trouble clinically or not; yet, he is no surer in this case than he is in the case of the tuberculous patient. The answer to this is that the tuberculin reaction is not absolute, but the Wassermann is. How has this been proved? Is not a hidden active tuberculous focus as dangerous as a hidden active syphilitic focus, and is not a hidden active tuberculous focus as dangerous as a detected one? Have we any grounds for belittling the danger of such a focus? The fact that all such foci do not become serious clinical entities and do not go on to the death of the individual, is not sufficient, and would not be accepted in any other field of medicine. The fact that tuber- culosis infects probably two-thirds of all who reach adoles- cence; and that it produces toxins which impair the health of a considerable per cent of those infected; and that it is the cause of death in about one-tenth of the world's population; and that it causes a morbidity four times as great as its mortality, should be sufficient to emphasize the importance of all such foci. If only we could determine in some manner how long specific 600 DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS cell stimulation or sensitization remains after inoculation, or particularly after healing of a tuberculous focus, then we could arrive at some definite opinion as to the value of tuberculin in diagnosis. Until such time, however, we are obliged to make our medical imagination, which when interpreted, means our ability to theorize and make clinical application of our theories, take the place of definite scientific facts. From many years of observation in the employment of the tuberculin tests, particu- larly in cases of pulmonary tuberculosis, the writer has de- veloped a firm belief in the value of these tests. If only we bear in mind that the reaction is an expression of specific cellu- lar defense against (cell sensitization) the bacillus and its specific products, we will understand the interpretation of the phenomena better. The von Pirquet or cutaneous test is the one that I prefer to use and the one which I think is easiest of interpretation. It is thoroughly established, according to the observations made in the study of immunity, that an individual fights infec- tion by creating a specific cell defense. This specific defense is, to a certain extent, commensurate with the severity of the in- oculation and the reactive capacity of the body cells, which lat- ter is bound up quite closely, as far as we are able to determine, with the degree of health of the individual. All else being equal, the strong robust patient reacts best and the reaction is great- est when the infection is not too severe. If these observations are correct, barring the very severe inocu- lations, we should expect most active defense when there is the greatest need, that is, when fighting an active infection; and the greater defense, the more resistant the individual. We would also expect this defense to show as an increased sensitization (an increased specific defensive power) of the cells toward the bacillus or its products. Tuberculin, containing the specific bacillary products, should, then, when brought in contact with the body cells, provoke a reaction commensurate with the de- gree of specific sensitization (specific defensive powers) present, being greater when the patient's reacting power is good and when fighting an active lesion, and less marked when the lesion VARIABILITY OF TUBERCULINS 601 is quiescent, and, theoretically, at least, finally disappearing af- ter healing has occurred. This has been my experience in practice. By interpreting frank prompt reactions as positive evidence of an active tuber- culous focus somewhere in the body, one will not go far wrong. Such interpretation will not be farther from the truth than our usually accepted methods in other lines. This leaves a very important class of cases in doubt, however ; for there are individuals whose body cells fail to react properly in building up specific defense. In these, accurate diagnosis and proper therapeutic measures are even more important than in those whose defense is good, but the tuberculin test may prove valueless. This will be in a smaller proportion of cases than is generally believed. The cachectic, those severely ill, those with atrophied skin and those suffering from acute illness other than tuberculosis, particularly some of the acute infectious diseases, will remain in doubt. But, knowing this, why not use the test for the definite knowledge it gives. Every practitioner of medicine has certain limitations in diagnostic and therapeutic ability, but he does not refuse to examine and treat all diseases because of it. He secures other help to cover his weakness. Let it be understood that the power of bacillary products (tu- berculin) to seek out and stimulate specifically sensitized cells may be far more accurate than our power to locate and deter- mine the activity or quiescence of tuberculous foci; and, when such evidence is present, even though we have not been able to locate the lesion, let us accept it as a tangible proof of our limita- tions rather than an instance of nature's specific reaction gone wrong. Variability of Tuberculins. — At this point permit me to call attention to an important factor which is probably militating against exactness in the tuberculin tests. We know that differ- ent skins react differently; that the degree of reaction depends upon the reactive powers of the patient; that it is influenced by certain infections; and that it is further influenced by the method of making the test; but I desire to call attention to an- other source of difficulty in interpretation which lies in the tu- berculin itself. Tuberculin made by different manufacturers 602 DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS differs greatly in its strength and in the percentage of com- ponent parts of the tubercle bacillus which it contains. During recent years I have made a careful study of the character of the reaction following the von Pirquet test. In this I have used Koch's Old Tuberculin, full strength. I have found that the preparations made by some manufacturers would give a reac- tion twice or three times as strong as the tuberculin made by others. It is very desirable to have some method of standardiz- ing these reactions. If we have a tuberculin which contains comparatively few of the principles of the tubercle bacillus, which are active in producing a reaction, we can readily see that the maximum reaction from this preparation would be decidedly small, as compared with one which was rich in these active principles. After observing this fact I made the com- parison of several different preparations and found that the tuberculin made by one manufacturer gave a maximum reaction of % cm. in diameter, in the same patient in which a prepara- tion made by another manufacturer gave a reaction of IV2 to 2 cm. From this, it can be seen that the reaction of y 2 cm. would be considered a moderately severe reaction, when inter- preted in the terms of the second preparation. The importance of this is evident because a prompt maximum reaction accompanies activity in a tuberculous process in an in- dividual with good reactive powers, while a slight reaction com- ing on slowly, is rarely found in one fighting an active infection. The diagnosis of early active pulmonary tuberculosis is not an easy matter unless the infection possesses considerable viru- lence and results in the formation of many toxins, or the lesion is fairly extensive. We must disabuse our minds of the thought that we are diagnosing the disease as soon as it affects the pul- monary tissue. Occasionally it is weeks, but more often months and years after the implantation of the bacillus and the produc- tion of the first fibroid area that activity again shows itself, and an extension of the disease takes place with a production of the symptoms which we have learned to recognize as belonging to early pulmonary tuberculosis. The examination of the lung, however, can be approached in so many ways that when our data is all correlated, we are in a CLINICAL HISTORY AND DIAGNOSIS 603 position to give a fairly accurate opinion. By the time the in- formation obtained from clinical history, physical examination, sputum examination, tuberculin tests, and the x-ray are cor- related, the per cent of error will be no greater than in any other field of diagnosis, made by an examiner of equal skill. Importance of Clinical History in Diagnosis. — The importance of obtaining an accurate clinical history seems to be generally underestimated, at least in practice. While it is true that some of the symptoms of which the patient complains are of little differential diagnostic worth and could be produced by other pathological conditions, yet there are others that have greater significance. If the history is carefully and fully taken, there will usually be enough symptoms elicited to point definitely to a pulmonary tuberculosis and make such a diagnosis a probability. In the grouping of symptoms according to their etiology 1 I have endeavored to show the relative importance of the different groups of symptoms of early tuberculosis and their diagnostic value. Those due to toxemia such as malaise, feeling of being run down, lack of endurance, nervous instability, indigestion, and loss of weight, rapid heart action, night sweats and temper- ature do not point to anything definite. They could be caused by a pulmonary or a glandular tuberculosis or a lesion in most any tissue of the body, or to a non-tuberculous toxemia of light degree. Consequently, they alone are of little diagnostic aid. But, when the lung is involved, they rarely occur alone. One or more of those of reflex origin, such as hoarseness, tickling in the larynx, cough, indigestion with loss of weight, chest pains, particularly aching of the shoulders and over the apices and upper portion of the lung, increased pulse rate and flushing of the face, are almost sure to be present if the focus is active; so, also, one or more of those due to the tuberculous process per se, such as frequent and protracted colds, spitting of blood, pleur- isy, sputum, and rise of temperature. Hoarseness or tickling in the throat, when due to a tubercu- lous irritation, with or without cough or expectoration, is nearly J The Altered Condition of the Neck and Chest Muscles and Subcutaneous Tissue Over- lying Them as Important Aids in the Early Diagnosis of Tuberculosis, Northwest Medicine, 1915, vol. vii, No. 6, June; and A Classification of the Symptoms of Early Pulmonary Tuberculosis Based on Their Etiology, St. Paul Medical Journal, 1915, vol. xvii, No. 1. 604 DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS always accompanied by some of the toxic symptoms above men- tioned, and this combination should point to the lung. Local lesions in the larynx of a simple nature which cause persistent hoarseness or inclination to cough are not apt to be accom- panied by toxic symptoms. When sufficient irritation is pres- ent in the lung to produce reflex hoarseness and cough, either the diaphragm reflex or the spasm of the superficial muscles, or both, are practically certain to be present ; and, if so, add greatly to our suspicion of an inflammation in the lung. The more ex- perience I have in the study and employment of the reflex motor phenomena, as they are found in active pulmonary tuberculosis, the more I depend upon them when in doubt. A failure to appreciate the nature and cause of the symptoms and signs which accompany tuberculosis has caused great con- fusion in the examiner's mind and made the diagnosis of this disease extremely difficult. Now, however, that we have classi- fied them etiologically, we can better understand the different manifestations of the disease and form a more accurate concep- tion of the underlying pathology as expressed in the symp- tomatology. In all organs which are supplied by the sympathetic division of the vegetative system on the one hand, and the greater vagus on the other hand, there is very likely to be during periods of toxemia, a general depression of function, because the sympathetics, being centrally stimulated, produce such an increased tonus that they are able to overcome the vagus tonus and destroy the normal physiolog- ical balance. The importance of understanding the nervous system in both its relationship to the lung and to the toxins engendered by the tuberculous process cannot be overestimated. Two of the groups of symptoms which I have described are expressions of nerve stimulation. The symptoms in one of these groups, — those of toxic origin — are due to central stimulation; while the other, — those of reflex origin, — are due to peripheral irritation. This difference, naturally, stamps these groups with a distinct in- dividuality. In this connection, however, we must not forget the peripheral stimulation of the sympathetics resulting from adrenin. CLINICAL HISTORY AND DIAGNOSIS 605 Symptoms belonging to Group I (toxemia) are expressions of central stimulation plus a general discharge through the sympathetic nervous system and manifest themselves in many organs and tissues at the same time. They are also present under several conditions. 1. When bacilli in the tuberculous focus are multiplying and toxins are diffusing into adjacent tissues ; likewise when necrosis and caseation are taking place. 2. When, after the acute inflammation has disappeared, through wrong methods of living, particularly overexertion, autoinocu- lation produces sufficient toxemia to continue the irritation of the sympathetic nervous system. 3. When, through prolonged action of the toxins the normal sympathetic balance has been more or less permanently dis- turbed and a condition of neurasthenia has developed. 4. When, through fear, discouragement and disappointment, as a result of the disease or for some other cause, general sym- pathetic stimulation takes place. While toxic symptoms are due to central stimulation of the sympathetics, and are prolonged by peripheral stimulation by adrenin, reflex symptoms are produced by stimulation of the peripheral endings of the greater vagus and possibly also the sympathetic divisions of the vegetative system in the inflamed area in the lung. These symptoms are also widespread, affect- ing many tissues and parts; but they express themselves with a wide degree of variability. At one time or in one organ the symptoms may be the expression of a vagus reflex, while at an- other time and in another organ they may be that of a sympa- thetic reflex. When the action of both divisions affects the same organ, as it does in the heart, stomach and intestines, vagus tonus may predominate at one time and sympathetic at another; and at still other times, the stimulation through the two systems may balance each other and maintain a normal equilibrium. When acute toxemia is present the central stimulation of the toxins on the sympathetic, added to the peripheral irritation of the sympathetic nerve endings by the increased adrenin in the blood and possibly also by the inflammation in the lung, over- 606 DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS balances the vagus tonus in nearly every instance, with a result- ant general depression of function in the viscera. We now and then see notable exceptions to this rule, however, in that the pulse rate will remain lower than is common in other fevers, of equal degree, during acute cavity formation in the lung. Hyperacidity will now and then also increase in severity during this stage of increased toxemia. The explanation for this is that the reflex irritation of the greater vagus is sufficient to preserve a strong condition of vagus tonus; if not sufficient to overcome the effect of the sympathetic, at least sufficient to greatly modify it. The absence of symptoms of the toxic group does not mean that active tuberculosis is not present. The symptoms due to reflex cause are variable; at one time a sympathetic tonus may be most prominent; at another a vagus reflex may predominate in the same organ. When the condi- tions which are accountable for the toxic symptoms disappear, the remaining symptoms depend on whether vagus or sympa- thetic tonus predominates. We now find a rapid pulse due to increased sympathetic tonus; now one slower than normal due to increased vagus tonus; now depressed secretion and motility in the stomach and intestines as a result of increased sympathetic tonus ; and, again, an increase in both functions due to increased vagus tonus. This antagonism is present as long as the peripheral nerve endings in these two systems are irri- tated and the central cells are stimulated. We should probably not go far wrong if we assumed that permanent injury follows this chronic stimulation; and, that some of the degenerative changes which manifest themselves in the internal viscera of the patients suffering from chronic tuber- culosis, are due to this reflex irritation. We have analogous grounds for suspecting degenerative changes in the internal vis- cera, in the trophic disturbances which manifest themselves in the skin, subcutaneous tissue, and muscles, as a result of reflex sympathetic irritation, as already described. The symptoms due to the tuberculous process per se are the most trustworthy symptoms in early pulmonary tuberculosis, and one, or more, is usually present comparatively early in the disease, although they rarely show as early as those of toxic CLINICAL HISTORY AND DIAGNOSIS 607 and reflex origin. Frequent and protracted colds are common- ly present, but rarely occur except when a fairly extensive lesion is present; but, when present, should always make us think of pul- monary tuberculosis. It is nearly always accompanied by some rise in temperature and some of the symptoms of the other two groups. Spitting of blood makes the diagnosis almost positive un- less some other cause can be found ; so does pleurisy. Pleurisy and spitting of blood may both come on suddenly with few or no symp- toms belonging to the other groups, although, of the two, pleurisy is more apt to be so accompanied. If, instead of calling pleurisy by its simple name we would call it by its true name, active tuberculosis of the pleura, we would have far more respect for it and often give our patients the advantage of diagnosing a tuber- culous involvement when it first announces its presence. Sputum containing bacilli, while rarely present, may be found, occa- sionally, very early to the great surprise of the examiner. This follows sufficiently often to make it imperative on the examiner to collect all sputum raised by the patient, regard- less of his opinion as to where it comes from, and subject it to one of the more accurate tests for bacilli. A three days ' quantity should be taken in all such cases and treated as described fully in Chapter XX. Temperature as a diagnostic sign in tuberculosis has lost some of its long time suspected value. Formerly, clinicians were will- ing to make a diagnosis of tuberculosis on a slight persistent rise of temperature which could not be assigned to any other cause, even if no other sign of the disease could be found. Now, that we know there are many lesions of localized infection such as those produced by microorganisms of the streptococcus type, which may cause persistent slight elevation of temperature, we are coming to realize that differentiation is necessary. Such rises in temperature must be looked upon as being a part of the general syndrome of toxemia, and as such, may be caused by infections of the tonsils, teeth, sinuses, prostate, fallopian tubes, or any other organ. In instances of hidden tuberculous foci and hidden infections of other types, differentiation may be very difficult for we may have the same group of toxic symptoms and the same type of 608 DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS temperature curve. In such cases the value of the tuberculin test must not be forgotten. A positive well marked cutaneous reaction indicates such a sensitized condition of the cells as ac- companies an active tuberculous focus; or a reaction to the sub- cutaneous injection indicates the same. Of course, infections of both types might be present and this possibility must not be over- looked. From our discussion it is now plain that the only group of symptoms which, unaided, permits of the making of a definite diagnosis are those belonging to the group caused by the tuber- culous process per se. But, fortunately, if the history is taken with sufficient care, any one important symptom or any group of symptoms will most likely be fortified by others. A fact which is often lost sight of is that it is just as important to question the patient further regarding points in his clinical history in case of doubt, as it is to reexamine the chest, or sputum. Pa- tients are rarely able to give a complete, accurate, clinical his- tory upon the first interrogation. What Value Has Physical Examination in Diagnosis? — The physical examination of the chest is the procedure upon which the decision as to the presence or absence of pulmonary tuber- culosis finally rests. When one recalls the few changes which small early lesions cause in the pulmonary tissue, and the dif- ficulties which beset the usual methods of examination, he is forced to believe that reliance on physical findings by men with insufficient training or experience is militating against truly early diagnosis. This is particularly true with our present short- comings in physical diagnosis. This is not said to discourage the making of physical examinations, but in recognition of a fact which is militating against early diagnosis. With the more intensive teaching of today, however, there should be no more excuse for failing to examine chests properly than for failure in any other line. As long as we are led to believe that early pulmonary tubercu- losis is easy to find on physical examination, so long will exami- nations be made, and, failing to discover a lesion, the patient be told that his lungs are free from tuberculosis. Expert examiners are beginning to realize that the truly early cases cause ex- PHYSICAL EXAMINATION AND DIAGNOSIS 609 ceedingly slight changes in the tissues; and that the truly in- cipient pulmonary tuberculosis — that entity concerning which they have talked and dreamed — is so unfamiliar to them that they would scarcely recognize it when making examinations by the usual physical methods. The findings on physical examination of moderately advanced tuberculous lesions are fairly well known. They have unfor- tunately been described as belonging to incipient tuberculosis. This fact can be appreciated when we fully realize that adult pulmonary tuberculosis is a chronic infection; at first, usually small and fibroid in character, because it is an infection which takes place after the patient has become partially immunized against the bacillus. The protective sensitization of the cells prevents it from extending rapidly. Its very slowness of develop- ment minimizes the symptoms present ; and so the disease usually arrives at such a degree of activity that exudation has taken place in the surrounding tissues, the lesion has become some- what extensive and conditions are present for a fairly rapid pro- gression of the process before it is recognized clinically. Instead of calling this incipient tuberculosis, it is more appropriately named clinically active tuberculosis. This offers signs which may be detected by the usual methods of physical examination; but even this is not always easy to detect. This process may follow months and even years after the incipient lesion. The lesson that this impresses upon us is to realize the short- comings of our older teachings and improve upon them. It emphasizes the fact that signs on percussion and auscultation may be so slight as to go unrecognized, yet a tuberculous lesion be present. Progress is not apt to be made unless the necessity for such is recognized, and it is in that spirit that we approach this difficult subject. If all who examine chests would only ap- preciate these difficulties, as those do who are expert examiners, and, in case of doubt, make the final diagnosis not so much on the physical findings alone as from a careful analysis of all the data derived from clinical history, physical examinations, tuberculin tests, sputum examinations, and x-ray findings, the results from the standpoint of the patient would be far more satisfactory. 610 DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS There is no use disputing over the character of the breath sounds in early tuberculosis, for it may be rough; it may be harsh ; it may be both ; expiration may be prolonged or not. The character of the sound will vary according to the condition of the tissues, whether it be a new lesion or a lighting up of an old focus, and upon the extent of both the old and the new, when present, as described on page 429. The same may be said of percussion. The normal side may show the highest percussion note when the soft structures on the other side have atrophied, as they do in the presence of chronic inflammations in the lungs, as described on page 422. In case an active clinical pulmonary tuberculosis is suspected from clinical history, and yet the diagnosis is in doubt on ac- count of negative findings on auscultation and percussion, I would suggest that its presence or absence can almost certainly be determined by the presence or absence of the diaphragm re- flex (lagging of the side) and the motor reflex (spasm) as it affects the neck and chest muscles, particularly the sternocleido- mastoideus, trapezius, and levator anguli scapula?, as described on page 410. "While these alterations in function may be produced by any inflammatory condition in the lungs, yet they are ex- tremely important in their diagnostic weight when tubercu- losis is suspected from other signs and symptoms, and while most of the early symptoms are temporary, these muscle changes (spasm) last as long as the sympathetic endings are irritated by the inflammation in the lung. An acquaintanceship with the motor and trophic reflex as af- fecting the muscles of respiration including the diaphragm and the skin and subcutaneous tissue covering the neck and chest muscles, as described on page 405, will afford the examiner^ most helpful information in these difficult cases. The position of the sputum . examination in the diagnosis of what is usually termed early tuberculosis can be made of far more value than it is. The common methods of taking only a sample, or even telling the patient to clear out his throat mucus in the morning and save that immediately following, are subject to great error. In these early cases bacilli may be present, but they are not apt to be present in all the mucus raised. The sur- X-RAY AND DIAGNOSIS 611 est method of finding them consists in taking a twenty-four hour, or a three day, sample and digesting and homogenizing it as men- tioned on page 534. In this way the error is greatly minimized. Sometimes when bacilli are absent a high lymphocyte count may be present (Wolff-Eisner). This is extremely suspicious of tuberculosis. So is the albumin content in the sputum of some diagnostic merit. The X-ray in the Early Diagnosis of Tuberculosis. — Various opinions are held regarding the value of the x-ray in the diag- nosis of early tuberculosis. It is of great value when used by an expert. It must always be remembered that it has serious limitations. No one except an expert should make a diagnosis of clinical tuberculosis from an x-ray plate alone. The findings may be positive, yet the process may be healed. If, however, clinical symptoms are present and physical signs particularly reflex motor disturbance and x-ray findings are positive, then the x-ray is of value in giving important confirmatory evidence. The x-ray as used by the average operator gives no reliable data on which to base a diagnosis of truly incipient tuberculosis. There is no doubt, however, that even a poor x-ray will make the diagnosis earlier than many of the careless clinical examinations. It is on a par with a poor physical examination. The best work in pulmonary rontgenoscopy, however, as studied and compared with the best work of clinicians, the comparison being made by the clinicians themselves, has helped to elucidate many problems and has advanced the science of diagnostics very materially. The x-ray is particularly valuable in hilus lesions; and in this con- nection I desire especially to emphasize its value in the diagnosis of tuberculosis of the bronchial glands in children. But here the findings are of real importance only as they are taken in con- nection with the clinical history. For further discussion see Chapter XIX. The fluoroscopic examination of the chest is important. The study of the motion of the diaphragm will often give valuable information. The patient should be observed both during quiet and forced respiration, remembering that a limited excursion of the diaphragm may show on quiet respiration and be entirely overlooked on deep breathing. 612 DIAGNOSIS AND DIFFERENTIAL. DIAGNOSIS DIFFERENTIAL DIAGNOSIS. General Asthenic Constitution. — It is often difficult to deter- mine whether or not a person of general asthenic build is also suffering from a tuberculous infection. Such individuals show many of the characteristics of the one with semi-quiescent tuber- culosis. The want of energy, lack of endurance, and gradual de- velopment of the irritable nervous state, coming on as they so often do in both conditions immediately after puberty, makes them extremely difficult to differentiate at times. If tubercu- losis is primarily the cause of the asthenic condition, or if it is present as a complication, it often remains of the hidden type for a long time. Even if localized in the lungs it may not be detected early owing to its slow progress. In the case of hid- den tuberculosis the tuberculin test becomes a very important diagnostic measure; and, even it may prove of negative value. Under such conditions a probable diagnosis is all that can be made. If the infection is in the pulmonary tissue, the doubt should be removed by methods already mentioned in the early part of this chapter. The reflex signs and symptoms, and the symptoms due to the tuberculous process per se are of far greater diagnostic value than those of toxic origin in these cases, and, when present make the diagnosis easier. Neurasthenia. — Neurasthenia may be caused by many different conditions, including tuberculosis. At times it offers the same difficulties of diagnosis as the general asthenic condition. Its re- lationship to the toxemia of tuberculosis must not be lost sight of. A hidden or unsuspected tuberculous lesion is often the un- derlying cause and should always be considered where the etiology of neurasthenia is vague. See Chapter VI for a more complete description of this relationship. Malaria. — Malaria is particularly confusing in districts where prevalent. The toxic symptoms of early active tuberculosis so closely resemble those of malaria that it is no wonder that er- roneous diagnoses are made. Care on the part of the examiner, however, will differentiate the two, particularly if the lesion be pulmonary. Finding the parasite in the blood settles the diag- nosis. One should remember, however, that both may be present. BRONCHITIS AND TUBERCULOSIS 613 Acute or Subacute Bronchitis. — The differentiation between simple bronchitis and early pulmonary tuberculosis is at times difficult to make, particularly if the bronchitis is prolonged in its course. Bronchitis often comes on as a cold in the head or infection of the upper respiratory tract and extends downward, although at times the first symptoms are on the part of the lower tract. Tuberculosis, on the other hand, begins in the lungs. In bronchitis the attack is apt to be more sudden in its onset and the symptoms more severe, although this varies greatly with different attacks. Cough usually appears suddenly and is har- assing in bronchitis, while it is of gradual onset and milder in tuberculosis. Temperature is usually elevated at first and drops after a day or two in bronchitis ; but it is persistent if due to ac- tive tuberculosis; or, if due to a sleeping focus which has been aroused to activity. Kales may be present, either fine, or coarse and bubbling, or dry sonorous, or sibilant in bronchitis, and are, as a rule, scattered over considerable lung area; while in tuber- culosis they are confined to a smaller circumscribed area, usually near the apex, and are accompanied by percussion changes and disturbed function on the part of the diaphragm and other re- spiratory muscles. The motor reflex is not present in bronchitis unless pulmonary tissue is inflamed. The tuberculin test is often of value when sputum is absent. A bronchitis, accompanied by toxic symptoms, which persist for more than a few days, is sus- picious of tuberculosis. Intercostal Neuralgia. — The diagnosis of intercostal neuralgia is often made when tuberculosis of the pleura is the pathological process present. Intercostal neuralgia is an exceedingly rare condition per se, while tuberculous pleurisy is common. Judg- ing from the diagnoses made, the opposite would seem true. Any pain which seems like an intercostal neuralgia should be investigated for pleurisy (tuberculosis of the pleura). One im- portant differential point is that the motion of the lung is more restricted in pleurisy than in intercostal neuralgia, and the pain is more acute on respiration. It must be remembered that there can be an inflammation of the pleura without any marked signs. Both pain and the pleural rub may even be absent. 614 DIAGNOSIS AND DIFFEEENTIAL DIAGNOSIS Influenza. — Sometimes clinical tuberculosis is suddenly ushered in with symptoms resembling those of influenza. This usually comes in one who has been somewhat below par for a time, yet in whom the symptoms were so slight that they were not recog- nized until the more acute symptoms manifested themselves. A chill followed by fever and other toxic symptoms, cough and free expectoration, all within a few days, is the picture. The exami- nation of the sputum in such cases usually affords a surprise to the unsuspecting clinician and makes the diagnosis. The motor reflex as shown in diminished action of the diaphragm and in- creased tonicity of the neck muscles is present and of value in showing that pulmonary tissue is involved in the inflammation. These attacks are all the more confusing if they come, as they often do, during the season when influenza is prevalent. Aside from the influenzal type of onset, there is a close re- semblance between the usual exacerbation in tuberculosis and influenza. Tuberculous patients often complain of repeated at- tacks of la grippe. Under such circumstances, the very fact of the repeated attacks should arouse suspicion that the process is probably of a tuberculous nature, and cause the sputum to be carefully searched for bacilli, and other means of differentiation to be used. Chronic Purulent Bronchitis and Bronchiectasis. — Not only are there difficulties in differentiating between early tuberculosis and other lesions in the lung, but even advanced tuberculosis must often be differentiated from other widespread non-bacillary in- fections. Chronic bronchitis and bronchiectasis, with the large quantities of sputum which are often present, and the evidence of loss of tissue and cavity formation and the tendency to exacerbation, is often extremely difficult to differentiate from tuberculosis. The difficulty is increased by the fact that chronic tuberculosis may be accompanied by large quantities of sputum, and yet not show bacilli. Cavities, at times, suppurate long after bacilli disappear. On the other hand, cases may be free from bacilli for years and be considered as simple bronchitis and then show bacilli. A patient who had been under the care of a confrere for fourteen years recently consulted me. At no time had CHRONIC FIBROSIS AND TUBERCULOSIS 615 bacilli been found in the sputum. Immediately prior to her consulting me, she had a rise of temperature and suffered from malaise and loss of weight. To her great surprise bacilli were found. Three possibilities must be considered in this case; the first, that this was a case of chronic bronchitis which eventually involved tuberculous tissue causing a breaking down of the protec- tive envelope with the escape of bacilli ; second, that it was origi- nally a tuberculosis which left the patient with a suppurating cavity from which the bacilli disappeared not to return again until the time of her consulting me; and, third, that bacilli were given off from time to time during active periods without be- ing discovered. Previous examinations had always been con- fined to the examination of a sample of sputum, while I took a twenty-four hour specimen and submitted it to digestion, and homogenization with the shaking machine before making the slide. I wish to urge the importance of such a procedure in all such cases as being far more satisfactory than the examination of single or repeated specimens. The patient also responded promptly to the cutaneous tuberculin test with a marked re- action, and from this alone I would have felt sure that there was an active tuberculous element in the case. In order to fully understand the necessity of examining twenty-four or seventy-two hour specimens after homogenization, see Chap- ter XX. Chronic Fibrosis. — We often find an increased density of tis- sue over a considerable portion of a lobe, usually the upper, when making a physical examination of the lung. Sometimes it is more marked near, and extending some distance into the lung tissue from the hilus. Auscultation often reveals a diminished murmur at times with increased harshness and sometimes with prolonged expiration. Such a condition may be present for a long time without producing recognizable symptoms, although usually there is a gradual impairment of health. I am coming to believe that most of such cases are tuberculous in nature from the first, and that they are produced by an organ- ism of low virulence which stimulates to new tissue formation instead of necrosis. Sooner or later, however, these processes undergo necrosis and assume the usual fibro-ulcerative type. The 616 DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS diagnosis in these cases is rarely made until necrosis occurs with the appearance of bacilli in the sputum, although this is usually preceded by a history of general decline in health lasting for a variable time. The x-ray is of value in these cases but is rarely employed unless accidentally, for it is rarely that the lungs are suspected, because there are no particular signs except those of gradual loss of strength until the temperature stage which pre- cedes or attends ulceration is reached. Pulmonary Infarct. — An infarct of a small pulmonary ves- sel may at times be difficult to differentiate from a tuberculous lesion. When the source of the embolus is plain it is not so difficult; but, if the seat is hidden, as, for example, in one of the deep veins, doubt may arise. If it is a large pulmonary vessel which is occluded, physical signs may be detected; but on the other hand the vessel may be so small as to preclude any changes in percussion or auscultation. If near the surface, pleu- risy is usually present, and motor disturbance on the part of the diaphragm will be noted. Bales may or may not be present according to the size of the infarct. Pain is the most common symptom. It is usually the first one noticed. It resembles the usual pain of pleurisy; which means, that it shows great vari- ability. It may be dull or sudden or sharp in onset; and may, particularly if it affects the diaphragm, be felt in the upper ab- domen and shoulder. It may be a slight discomfort or an acute pain brought on by cough and deep breathing. Expectoration of blood is a common symptom and only secondary in importance to pain. The blood may be slight in amount, or very profuse. It rarely shows as bright blood, but usually as tenacious, dark clots. With such symptoms it might be quite difficult to deter- mine whether or not tuberculosis or embolism is the cause. The character of the blood and the previous history of the patient are important factors. The fact that infarcts are more apt to oc- cur in the lower lobes, while tuberculosis usually affects the up- per lobes first, is also important. In infarct the symptoms are usually more sudden than in tuberculosis. The fact that infarct usually comes on in patients with cardiac disease or venous thrombosis is especially suggestive. Infarct usually runs a course PNEUMONIA AND TUBERCULOSIS 617 with slight or no fever, but so does tuberculosis at times. The tuberculin test may give important information. Pneumonia. — It is a very common experience for physicians, on being called to see a patient for the first time, to make a diagnosis of pneumonia if they find fever present and an altered percussion note over the chest with rales in the underlying lung. This diagnosis is made all too readily. The preceding history should be taken into consideration, the mode of the onset in- quired into and the whole symptom-complex should be carefully analyzed before such a diagnosis is made. Pneumonia, usually, begins with sudden onset, while tuber- culosis usually shows a definite history of antecedent decline in health. A careful history alone should nearly always prevent a mistaken diagnosis. For the symptoms of tuberculosis to be so pronounced as to be mistaken for pneumonia, with the excep- tion of those acute exacerbations which simulate influenza, there should be a definite antecedent history showing the presence of some of the most important symptoms extending over a period of weeks and often months. Malaise, lack of endurance, and feelings of gradual loss of strength would usually precede such a widespread infection, while cough and temperature could hardly be expected to be absent. Careful examination should also reveal the fact, if the focus is of tuberculous origin, that it began at or near the apex of the lung ; while, if it is pneumonia, the signs are usually in the middle or lower portion of the lung, although either may begin in any part. Lobar pneumonia is usually readily diagnosed, but broncho- pneumonia is the one which offers difficulties and is more often confused with tuberculosis. Physicians seem to dread making a diagnosis of tuberculosis if they can avoid it; the habit is all too common of calling any acute disease in the lungs either bronchitis or pneumonia. The curability of early tuberculosis and the seriousness of late tuberculosis, should be sufficient to compel that the tuberculous patient be given the benefit of the doubt. The examination of the sputum will usually be sufficient, if care- fully made, to reveal the bacilli. They are nearly always pres- ent when such acute symptoms occur. Repeated examinations should be made if the first are negative. A negative result on ex- 618 DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS amination, however, does not preclude the tuberculous nature of the disease. If the diagnosis is not made during the acuteness of the ill- ness, a delayed convalescence should make the diagnosis almost certain. The tuberculin test is unreliable in differentiating these con- ditions because tuberculosis may not give a reaction during the acuteness of the process. A marked reaction, on the other hand, would give valuable information. The test should be employed, but too much reliance should not be placed on the evidence ob- tained. Pulmonary Syphilis. — Pure syphilis of the lung is not a com- mon disease, yet it is one that must be differentiated from tuber- culosis at times. It is not unlikely, however, that the two dis- eases are at times found coincidentally. It is well to bear in mind that no one has been able to con- trol his ancestors and consequently anyone may be infected with syphilis; and no one has been able to control his environment during early years, consequently anyone may have tuberculosis. These diseases may be associated or they may be found inde- pendently. Each of them might infect the lung. Tuberculosis usually affects the lungs in adults; syphilis usually affects non- pulmonary tissues. Points of differential value in diagnosis are : tuberculosis usually begins at the apex, while syphilis usually begins at the hilus or base. Syphilis elsewhere in the body, with a typical pulmonary infection starting at the hilus or base, unaccompanied by bacillus bearing sputum, forms a basis for the diagnosis of syphilis; so does a positive Wassermann with negative sputum and negative tuberculin tests in atypical lesions. The thera- peutic tests are of some value. Prompt improvement under anti- syphilitic treatment suggests a syphilitic process. The symptoms of advanced syphilis may not differ in any particular from those often observed in tuberculosis. This can be appreciated when it is recalled that the symptoms of pul- monary tuberculosis are extremely variable. As a rule, the symptoms are less acute when of syphilitic than when of tuber- culous origin for the same amount of pathologic change. PULMONARY SYPHILIS AND TUBERCULOSIS 619 Landis 2 discusses this subject as follows: ''In acquired syphilis most writers describe two main types of the disease as it occurs in the lungs; namely, the formation of gummata or an extensive cellular infiltration which leads to fibroid changes. If the disease assumes the indurative type, and this is by far the most common form, it usually originates at the hilus of the lung and extends outward along the bronchi and blood vessels. The process is usually unilateral, and at most involves only a portion of one lobe; if several lobes are impli- cated it is the portions which adjoin the root of the lung. "In addition to these types a focal form has been described in which the lesion consists of an area of consolidation and catarrh. It is usually situated around the root of the lung, and may oc- cur at one apex. "Whether the disease manifests itself in the form of gummata, as a diffuse fibrosis, or as a focal lesion, most of the cases re- ported indicate that the base of the lung or the area about the hilus, rather than the apex, is the part most frequently attacked. This fact is usually cited as one of the strong differential points between syphilis and tuberculosis. The general opinion has been that the apices are rarely involved, but it would be rather sur- prising, in view of the wonderful diverse forms in which the localization of syphilis manifests itself, if the upper portions of the lungs should always escape. "We believe that pulmonary syphilis of a latent type occurs far more frequently than is usually supposed. The form to which we wish to call attention is that in which the localiza- tion occurs in the apices of the lungs. This type of the disease may simulate early pulmonary tuberculosis so closely as to de- ceive us entirely." In discussing the diagnosis, he further says: "It is to be noted that the symptoms in all of these cases were characteristic of pulmonary tuberculosis; namely, morning cough and expectoration, blood-streaked sputum; loss of weight, and a slight elevation of the temperature. In two there was pain re- sembling that occurring in pleurisy at the base of the right lung. 2 Latent Syphilitic Infection of the Lungs, American Journal of Medical Sciences, August, 1915. 620 DIAGNOSIS AND DIFFEKENTIAL DIAGNOSIS Furthermore, they all had physical signs indicative of incipient tuberculosis. "If the lungs are involved, there is, in addition to the symp- toms mentioned above, cough, which may be dry and unproduc- tive or accompanied by a moderate amount of greenish or yel- lowish expectoration. Blood-streaked sputum may also occur. Pain at the base of the right lung is not infrequent and may be misinterpreted; it is usually due to a syphilitic perihepatitis and not to pleural innammation. "The presence of latent syphilis of the lung is to be suspected if in addition to pulmonary symptoms there are present else- where in the body lesions which are in all probability luetic in nature, such as a periostitis, orchitis, iritis, or suspicious throat lesions. The recognition of these cases should be relatively easy. "The type of the disease which offers the most difficulty, and which, for the most part, escapes detection, is that in which the symptoms are entirely pulmonary and in which there are no as- sociated syphilitic lesions. "The diagnosis must be made by exclusion. Thus if the symp- toms and physical signs are those characteristic of tubercu- losis, and the sputum does not contain tubercle bacilli, or the progress of the case differs from that usually encountered in tu- berculosis, the possibility of some other exciting cause should be thought of. Not only should the sputum be examined for organisms other than the tubercle bacillus, but in addition, a Wassermann test should be made in every doubtful case." Actinomycosis. — This affection must sometimes be differenti- ated from tuberculosis. The differentiation depends on finding actinomyces in the sputum. In symptoms and signs the dis- ease is much the same as many of the atypical cases of tuber- culosis. Cough, sputum, at times accompanied by blood, dyspnea, night sweats, and failing strength are the usual symptoms. The sputum was very fetid in one of my cases, while in another it did not differ especially from that of tuberculosis. This affection is often found at the bases instead of the apices, although it may affect the latter. Negative tuberculin reactions and a failure to find bacilli are only negative evidence. They do not afford any positive diag- MALIGNANT TUMORS AND TUBERCULOSIS 621 nostic data. The finding of actinomyces is necessary for diag- nosis. Streptothricosis, Blastomycosis, Aspergillosis, and Coccidioidal Granuloma are sometimes to be differentiated from tuberculosis. These diseases are rare but should be thought of when the pul- monary lesion is atypical. In comparison with tuberculosis they are so rare that they sink into insignificance; but, for accuracy of diagnosis, they must be borne in mind. Their diagnosis is made by finding the specific microorganisms in the sputum. Malignant Tumors of the Lung. — Malignant tumors of the lung may be either primary or secondary. Such primary growths, however, are comparatively rare. They may be either of the sarcomatous or carcinomatous type, the former occurring in early life, the latter in late life. Probably two-thirds of sar- comata occur before the fortieth year, and nearly all carcinoma after that time. Of ten cases of sarcoma and cancer of the lung seen by me, and of which I have notes, all were secondary but one. This was a primary cancer, taking its origin from the glands in the left superior bronchus. The others were metastatic ; one a carcinoma primary in the mediastinum; two, primary in the stomach; and three, primary in the breast. The other three were sarcomata; two, primary in the femur; and one, primary in the uterus. In one of the sarcomata the leg had been amputated for sarcoma nine years previous to the metastatic manifestations. These growths may extend throughout more or less of the lung, and also affect the pleura and structures of the mediastinum. The pericardium is not uncommonly affected. Pleural effusion is not uncommon and adds greatly to the discomfort of the pa- tient, particularly late in the clinical course of the disease. The symptoms vary greatly in different cases according to the structures involved. An irritating cougli which slowly increases in severity is common. This is at first unproductive or accom- panied by a small quantity of glary, pearly, or, at times, green- ish mucus; the latter being found rarely except when the dis- ease has become somewhat extensive. Dyspnea of a progressive nature is also common. This is especially emphasized on exer- tion. The patient may be comfortable when quiet, but, on chang- 622 DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS ing position, suffers from shortness of breath. Temperature, is, as a rule, not present early. I have seen a rise to 100° however, as the disease became advanced and showed signs of breaking down. Pain is, at times, a factor. In the case of my series, which was primary in the mediastinum, there was marked pain under the sternum and in the left arm. A very marked involve- ment was present in the pericardium in this case. In some of the other cases, sharp cutting pain like that of acute pleuritis was present; and, in two, considerable dull pain in the axillary region. A feeling of fullness and compression is particularly noticed where the growth spreads rapidly and where large pleural effusions are present. Hoarseness and aphonia may ap- pear when the recurrent nerve is directly involved. Difficult breathing or stridor is sometimes noted when pressure is made on the trachea. In differentiating cancer and sarcoma from tuberculosis it should be borne in mind that the toxic and most of the reflex symptoms present in the latter disease, are absent; and that, in cancer and sarcoma, the process in the lung is usually wide- spread for the clinical symptoms present. The patient may be in full weight until near the time that the process becomes fatal. On the other hand, I have seen cachexia and emaciation the same as in pulmonary tuberculosis. The physical signs present depend partly on where the growth is situated. In the centrally located growths there is increased resistance on palpation and percussion, as well as a dullness over the areas surrounding the hilus of the lung; while in pure pul- monary metastases there are either isolated or conglomerate tumor masses in the pulmonary tissue itself which if large enough produce the same changes. The side of involvement usually shows diminished motion. When located in the mediastinum pressure on the vessels at times becomes great and causes a dilatation of these on the surface. Auscultation may or may not show rales. Diminished breathing may be present when pressure is made by the tumor upon a bronchus and when air is excluded from the pulmonary tissue by the tumor structure. The supraclavicular, cervical and axillary glands may be the seat of metastatic infection. MALIGNANT TUMORS AND TUBERCULOSIS 623 The sputum may be blood-tinged at times. Sometimes frag- ments of the tumor are found, and sometimes clusters of cells which are considered as having diagnostic importance. The x-ray is- of value where its findings are correlated with that of physical examination and clinical history. Fig. 105 shows the x-ray plate of one of my cases. Diagnosis of primary cancer in the lung is not easy. In my case, the widespread lesion, with little or no sputum, comfort during quiet, with dyspnea on movement, absence of tempera- ture, and a peculiar feeling to the palpating fingers which was entirely different from tuberculosis caused me to make a diag- nosis of probable new growth in spite of the absence of a history of cancer in some other portion of the body. Later, tumor cells were found in the sputum and the case was proved postmortem. In the secondary metastatic tumors of the lung, the history of a previous tumor in some part of the body is suggestive. CHAPTER XXII. PROGNOSIS. Introductory Remarks. — There are many factors which must be taken into account in arriving at a prognosis, each one of which influences the chances for recovery, to a greater or lesser degree. It is but a few years since tuberculosis was considered an incurable disease. Today, however, clinical experience warrants the assertion that tuberculosis is not only curable, but that, when treated at the right time, and in the proper manner, it may be overcome and the patient be restored to health in a very large per cent of cases. Early clinical tuberculosis when properly treated, should have a mortality no greater than that of other common infectious diseases. The hopeful side of the tuberculosis problem has been well stated by Eisner. 1 In speaking of chronic tuberculosis, he says : "A large number of these cases are curable, many become la- tent; the vital fact which interests us in considering their future is that they can only be saved by early diagnosis and prompt treat- ment. Put in the resistance, bring the condition of the patient to par or above, and the disease, if it is in its incipiency, will be stayed in over eighty per cent of all cases, while twenty per cent of all forms of the disease are saved. To wait for definite physical signs before making a diagnosis darkens prognosis, for the pa- tient's chances are reduced thereby. To anticipate the final de- velopment in cases which are strongly suggestive, adds to the patient's chances. Positive physical signs are never early evidence of lung infection; they mean that the case is advanced." Age. — The prognosis differs according to the age of the pa- tient. The most serious age period for tuberculosis, all things else being equal, is the first five years after birth. During this period the patient is gradually developing a specific cellular re- sistance, and, until such time as this has been attained, the or- a Monographic Medicine, D. Appleton & Co., 1916, vol. vi. CONSTITUTION 625 ganism is not capable of overcoming large quantities of tubercle bacilli; consequently, if a severe infection occurs during this period, the patient has little chance of overcoming it. As shown by the statistics of Hamburger, quoted in Chapter IV, there is practically no tendency toward healing shown in patients suf- fering from tuberculosis during the first two years of life ; and it is only after the fifth or sixth year that the child begins to show an increased resistance. From that time on, we see more of a tendency for the disease to become chronic. By the time the child reaches the fifteenth year chronicity is manifested in one- half of the cases; and, after the fifteenth year, chronicity becomes more and more common; in fact, becomes the rule. Constitution. — While we have learned in recent years that tuberculosis is not an inherited disease, yet it is necessary for the clinician to take into consideration the constitution which is given to the individual at birth. While environment is prob- ably a much greater factor in the development of a child than heredity, yet there is no question but that heredity counts for something. The inheritance of a weakly constitution in an individual who lives in a poor environment, makes the worst com- bination possible. There are certain people who seem to be born with deficient nervous and physical mechanisms. Stiller has called attention to one type, asthenia congenita universalis. This type, he believes, is born with nervous and physical mechan- isms below par, even though the asthenic state does not develop until after puberty. Many individuals in whom a weakly consti- tution has been recognized in the past, do not inherit this consti- tution, but develop it after birth; in fact, many of those who are physically below par, and who are suffering from so-called phtJiisicus Jiabitus, are not fit subjects for infection, as is usually expressed, but have this habitus because of a previous infection. A person with a weakly constitution, naturally, should not be ex- pected to have as much resistance to disease as one who is physi- cally and nervously more fit; at the same time, it does not mean that those with weakly constitutions must be given up as hope- less, should they develop tuberculosis. It has been my lot to treat a great many patients with poor physique, who had developed tuberculosis; and, in case the in- 626 PROGNOSIS fection was not too severe, I have seen excellent results obtained in many of low physical and nervons vigor. Environment. — The environment in which the patient lives probably has more to do with prognosis than any other factor. This temi "environment" means so much that it comprises many other subjects which will be discussed in this chapter. I shall discuss environment, however, giving to it a limited mean- ing. If we discuss environment in connection with the physical surroundings of the patient we can see what an important ele- ment it is in prognosis. It further includes the home surround- ings, in which the patient lives, as well as his social and economic status. All of these are big factors in determining whether or not a patient with tuberculosis shall get well. Environment may be helpful, as well as harmful. If a patient lives in a stuffy room, with dead air, his opportunity for recovery is not as good as though he were in the open air. If he is surrounded by de- pressive circumstances, and depressive conditions, naturally, it will affect prognosis unfavorably. If the members of his family, and the friends with whom he lives, are cheerful and happy, and determined to aid him in carrying out his routine, his chances for recovery are far greater than where they are opposed to such a routine. It is possible to surround a patient in a home with cheerfulness and hope and give him encouragement, and so ar- range the physical features of the home as to aid; or they may be arranged so as to have the contrary effect. Good helpful en- vironment adds greatly to the patient's chances of cure; while antagonistic depressive environment makes the prognosis much less favorable. Economic Status. — Tuberculosis is an economic disease. It is found much more commonly among the poor than among the well-to-do, but exists in people in all stations of life. Now that we understand tuberculosis to be a disease which is transmitted through ignorance and willfulness, and, since infec- tion takes place largely in early life, and clinical tuberculosis develops from this early infection, it can be readily understood that the economic status of the individual is a big factor in prog- nosis. Ignorance and poverty go together, yet we find many ECONOMIC STATUS 627 worthy intelligent people among the poor, and find some of the grossest ignorance among the well-to-do. Poverty compels peo- ple to live under unsanitary conditions. It is necessarily accom- panied by an inadequate amount of food; and it deprives them of many of the healthful pleasures of life. Thus it acts by pro- ducing a general depression of the physical and mental capabil- ities of the patient. In those homes of the poor, in which overcrowding occurs, there is great danger of the disease being communicated to others; and, inasmuch as lowered vitality favors infection, this also operates to make transmission easy. Continued living under such circumstances makes those individuals who are already in- fected, more prone to have an extension or recurrence of their disease. We must conceive that tuberculosis is a disease which, taken into the body early, makes more or less effort in after years to extend to other tissues and parts. If the patient's resisting powers are low and his body cells are impoverished, they are not able to react with the same defensive force as the cells of those who are in better physical and nervous condition; consequently, the economic status of the people is a great factor in providing for their material wants, hence an important factor in the prog- nosis of tuberculosis. It is also important from the standpoint of treatment. Unless the state has provided adequate care for those who are ill, those whose economic status is low are unable to cope with the disease. Tuberculosis is a long drawn out dis- ease, the individual being an invalid and unable to work for a time averaging about two years. During all this time he must not only be cared for ; but, if he is the bread winner, the remain- ing members of his family must also be cared for or suffer ; con- sequently, if poverty is present at the beginning of the disease, it will grow worse as it continues. The state and the municipality have both begun to see their duty toward the tuberculous poor, and we now have provision made for many of those who are ill. Such provision, however, is still inadequate, and must be supplemented by private philan- thropy to as great an extent as possible until full provision is made for all. 628 PROGNOSIS While the financial condition of the patient is an important factor, yet this does not imply that the prognosis in the wealthy is better than in those of lesser means. On the contrary, it is often rendered unfavorable by other conditions which come with the possession of large means. It has been my observation that the best patients to treat are those of the middle class. Here we have intelligence, combined with enough means to care for the patient, yet we do not have to fight the ignorance which is so common among the very poor, and the willfulness which is so common among the very wealthy. Mental State. — The mental state of the patient is very im- portant in prognosis. Now that we understand the action of the depressing emotions in keeping up a prolonged stimulation of the sympathetic nervous system, and, through it, an inhibition of function on the part of many of the important internal vis- cera, we can offer a physiological explanation for a fact which has long been known; namely, that prognosis depends very much upon the mental state of the patient. The patient will often worry about some symptom which is comparatively unimportant. He will complain and become angry over the failure to have some little whim satisfied, when his very dissatisfaction and anger will do more harm than the conditions about which he was complaining. From a prognostic standpoint, hope, cheerfulness, and contentment are very important. THE CHARACTER OF THE LESION IN PULMONARY TUBERCULOSIS. Much could be written upon the subject of the character of the lesion in tuberculosis, but I will attempt to discuss it briefly from a practical standpoint. Miliary Tuberculosis. — Miliary tuberculosis is usually spoken of as being fatal. This is not true. In generalized miliary tuber- culosis this is true; but, in all cases of tuberculosis that are at all extensive, we have areas of miliary infection, which yield to the defensive powers of the patient. Miliary tuberculosis must not be confused with acute general miliary tuberculosis. The former refers to the small tubercles, while the latter refers to a FIBROID TUBERCULOSIS 629 dissemination of the disease more or less generally throughout the body, the infecting bacilli coming from a common focus and becoming implanted in the tissues at the same time. The former is favorable for cure; the latter practically hopeless. Fibroid Tuberculosis. — Now that we have studied more of the history of our infections in tuberculosis, and realize that they start in childhood, and gradually extend by secondary metastases, we have learned that infiltrations are often present for years without producing open active tuberculosis; but we are further coming to learn that there are types of infection which are com- paratively harmless during their early stage, but which take upon themselves ulceration and become serious as a later mani- festation. Not infrequently do we see lungs in which a gradual extension of the disease from one focus to another has been go- ing on over a prolonged period of time. Such patients, as a rule, show evidence of a chronic toxemia. -They have a deficient nerve balance; unstable heart's action; suffer from stomach disturb- ance, with a resultant malnutrition; and show a disinclination and inability to carry on work. They may have a slight rise in temperature at times, or they may not. Finally, after this stage of semi-invalidism has gone on for a period of time, — it may be a few years or it may be many years, — the patient is surprised by some such symptom as hemorrhage, pleurisy, repeated at- tacks of bronchitis, and probably expectoration which shows bacilli. Did we recognize this form of tuberculosis early, nearly every one of these patients could get well; but, as long as we delay our diagnosis until the more active symptoms manifest them- selves, just so long will we fail to do our duty by these patients by treating them at a time when the prognosis is favorable. We should bear in mind that chronic fibroid tuberculosis has as its terminal picture, in most instances, chronic fibro-ulcerative tuber- culosis ; consequently it demands early recognition and early treatment if it is to offer a favorable prognosis. Chronic Ulcerative Tuberculosis. — This type of tuberculosis in a pure form is rarely, if ever, found, because all chronic tubercu- losis must be accompanied by some fibrosis. What I refer to, however, is the type of tuberculosis in which the ulcerative form 630 PROGNOSIS predominates. We often see a patient who has had a previous infection in the lung, suddenly manifest acute symptoms with ulceration and cavity formation, and bacillus bearing sputum. From the first ulcerations, bacilli escape and form metastases; and repeated metastases follow necrosis and caseation of other areas. If this type of disease manifests a tendency to heal, it Mali sooner or later take upon itself a combination of the ulcera- tive and fibroid form. Areas will cease becoming necrotic and the stimulation of the fixed cells will result in the increase of fibrous tissue with a tendency to heal. Acute Caseous Tuberculosis. — This is the type of tuberculosis that we often see where there is a large area, — often a lobe, or more commonly, a portion of a lobe, in which the disease de- velops rapidly going on to necrosis. The infection in this type of disease often comes from plugging a bronchus with bacillus- bearing sputum. The infection is virulent because of the fact that a great many bacilli are implanted at the same time, and overcome the patient's resisting power. The entire tubercu- lous area is in the same degree of pathological change. This type is accompanied by a severe toxemia, which results in a breaking down of the patient's defense; consequently, the dis- ease usually develops rapidly. This type of tuberculosis sometimes offers a favorable prog- nosis. If widespread, however, as a rule, the toxemia is so severe that it proves fatal. I have often seen a caseous pneu- monia involving an entire lobe come to a state of arrestment. It did this by practically amputating the entire area of infection. Necrosis and caseation occurred and the entire mass sloughed out, leaving an empty shell. In such cases, if the process does not last too long, and if the tissues can slough out within a reasonable time before the patient's vitality is undermined, an arrestment may result. If, on the other hand, the toxemia con- tinues until the patient's metabolism is seriously interfered with, but one result can be expected, — a fatal termination. While there are many other forms of pulmonary tuberculosis that might be mentioned, yet these are the common types that are met with in every day practice. From the prognostic stand- point, the small lesion is most favorable. The small lesion is TUBERCULOUS COMPLICATIONS 631 nearly always fibroid in character. It is accompanied by little or no collateral inflammation, and little or no necrosis and caseation. It is much easier to attain a favorable result in the lesion which is small and of such a character that the danger of scattering the infection is comparatively remote than in the ex- tensive active one. TUBERCULOUS COMPLICATIONS. Not only must we consider the type of the pulmonary disease, but we must consider the complications which are present. It is possible to have a primary infection of almost any tissue or or- gan of the body, as I have discussed in the chapters dealing with the various tuberculous lesions ; nevertheless, nearly all infec- tions outside of the lymphatic tissues are metastatic in char- acter and must be looked upon as taking place after an in- fection has already existed in the body, and after the cells have taken upon themselves the property of producing defensive substances against the bacilli. Nearly all such lesions heal or become quiescent at first, because the number of bacilli produc- ing them is small, and the infiltration is not extensive. The prognosis, therefore, should be good, unless the infection is local- ized in tissue of such a character as to produce serious or fatal symptoms. Tuberculosis of the Larynx. — Tuberculosis of the larynx, in my experience, has always been secondary to an infection some- where else in the body, — usually the lung. The likelihood of a primary involvement of this organ is extremely remote. The infection is usually a surface infection, taking place from the bacillus-bearing sputum, as it comes from the ulceration in the lung. The prognosis of tuberculosis of the larynx depends both upon the character of the lesion in the lung and that in the larynx. The prognosis, barring those cases which are so severe as to interfere with nutrition, is about the same as that of the accompanying pulmonary disease. If the lung is actively in- flamed and undergoing a process of rapid necrosis and caseation, there is little chance of the tuberculous infection in the larynx healing, no matter how slight its character. On the other hand, 632 PROGNOSIS if the tuberculosis in the lung is arrested, or only moderately active, even severe ulcerations in the larynx may heal. If we speak of the laryngeal involvement as a process by itself, it may be said, the same as in tuberculosis of the lungs, that the prognosis is in proportion to the severity of the lesion. Slight infiltrations will nearly always heal if the condition of the pa- tient be fairly good and the pulmonary condition be not too ex- tensive nor too active; moderately advanced lesions will heal in a very large percentage of cases under similar circumstances; and severe lesions will heal occasionally if the lesion is located so that the patient can maintain his nutrition. Tuberculosis of Intestines. — Tuberculosis of the intestine is generally looked upon as offering an unfavorable prognosis. This is not necessarily true, although it must be considered a grave complication. A limited involvement of the intestine may be present for a prolonged period of time without producing serious symptoms, or without seriously interfering with the nu- trition of the patient. Under such circumstances healing occa- sionally occurs. I do not doubt that in many instances infiltra- tions in the bowel heal without their presence having been suspected. When the lesion becomes extensive, however, then digestion and assimilation is interfered with to such an extent that the prognosis is grave. I have a patient under my care at the present time who has had a tuberculous involvement for a year and a half or two years, the exact time I do not know. It was discovered at opera- tion eighteen months ago. At that time ulcerations were pres- ent from the pylorus to the descending colon. This patient has never had a diarrhea; neither has she suffered markedly with gas pains. She has, however, had difficulty in maintaining her nutrition. She has gradually lost weight and strength. One of the serious factors in tuberculosis of the bowel, from the prognostic standpoint is the fact that opportunity for re- peated surface infection is always present, and even though the part may be removed, the same likelihood of recurrence is pres- ent as existed prior to the operation. Pleurisy. — Pleurisy often causes an early diagnosis of tuber- culosis to be made and in this way causes the patient to secure TUBERCULOUS COMPLICATIONS 633 therapeutic aid at a time when the prognosis is good. Pleurisy itself also has a definite influence on prognosis at times. The average pleural adhesions at the apex probably make very little difference, as far as the patient is concerned, except as they cause intermittent intercostal pain and interfere slightly with the in- spiratory act; but a pleurisy with effusion at the base, which fails to absorb, and results in a general fibrosis involving the lung, proves decidedly unfavorable. So, at times, do wide- spread adhesions. Adhesions extending over the entire lung in- terfere greatly with the inspiratory act and in this way favor splanchnic congestion, interfering with the return flow of blood to the heart. The general venous congestion which shows it- self when widespread pleural adhesions are present, must also interfere with nutrition because perfect metabolism depends upon the normal rapidity of blood flow. Pneumothorax. — Pneumothorax, strictly speaking, is not a tu- berculous complication, yet it may be regarded as such because of the fact that it results so often from a rupture of a tubercle in the visceral pleura. Spontaneous pneumothorax is often looked upon as being an extremely serious complication in tuber- culosis. This has not been my experience. I have had favorable experiences following its appearance more often than otherwise. In the majority of cases that have come under my care, the pa- tient has not only recovered temporarily, but continued to make normal improvement after the complication had passed away. Tuberculous Meningitis. — Now and then a case of tuberculous meningitis is reported as having healed. There is no reason why this should not be true. A small localized tuberculous in- volvement in the meninges might exist without producing symp- toms of sufficient gravity to prove serious. In case the patient's resisting power is good there is no reason why healing should not occur now and then in small lesions. When the disease has become extensive and widespread, however, healing is beyond question. Meningitis is usually accompanied by an exudative process which produces pressure, resulting in deleterious symp- toms, and, sooner or later, death. Bacilli. — The presence or absence of bacilli in the sputum greatly influences the prognosis in tuberculosis. Eecently, a sani- 634 PROGNOSIS tarian of note, when giving a public address, made a statement which gave rise to the inference that patients with tubercle bacilli in their sputum are in a hopeless stage of tuberculosis. What he probably meant was, that as physicians, we have lost time and reduced the favorableness of the prognosis very ma- terially by not making diagnoses earlier ; but, it would be wholly wrong to let the impression go out that patients who have tu- bercle bacilli in their sputum cannot get well. There is no doubt of the difficulties which are met in endeavoring to bring about healing in patients who are suffering from open tuberculosis; but a large per cent of those who have but recently entered upon the open stage of the disease, with tubercle bacilli in their sputum, can get well if given proper treatment. The difference between the closed focus and open tuberculosis, however, from the prog- nostic standpoint, is a long step. The prognosis drops very rapidly after ulceration and bacillus-bearing sputum appears. There are two reasons for this: One, the increased danger of infecting other areas through the bronchi; the other, the in- creased difficulty of healing a broken-down necrotic area. The form of the tubercle bacillus has also been spoken of as having diagnostic significance. In our work in the Pottenger Sanatorium, after making careful examinations of sputum for many years with reference to the morphology of the tubercle bacillus, we have confirmed the idea suggested by Sewall many years ago, that the short bacillus accompanies activity, and the long bacillus is a representative of chronicity. This does not mean, however, that patients with short bacilli in their sputum cannot get well. We often notice an increase in the relative numbers of short, as compared with long bacilli, even in patients whose progress is favorable. It must be remembered that the lungs of patients suffering from advanced tuberculosis represent many different areas of infection, which differ in age. There are recent ulcerations, ulcerations moderately old, and ulcera- tions which have existed sometimes for months and years. The more recent ones probably throw off a preponderance of short bacilli, and the chronic ones a preponderance of long bacilli; consequently, we must expect a mixture of the various types; and, when we recall that the chronic ulceration had to go through TUBERCULOUS COMPLICATIONS 635 the acute stage, so may we expect these acute ulcerations to pass on to the chronic stage and produce the long type of bacillus. For further discussion of this subject see page 564. The Tuberculin Reaction. — Much has been written regarding the prognostic importance of the reaction to tuberculin, particu- larly the cutaneous and conjunctival reactions. Wolff-Eisner, dur- ing his many studies of the tuberculin reaction, claimed that the patient who reacted well to the conjunctival reaction offered a good prognosis. Others have claimed that a marked cutaneous reaction is prognostically favorable. This question cannot be discussed simply as a matter of reaction because it is necessary to take so many other things into consideration. I, personally, have always interpreted a good local reaction at the point of injection as giving evidence of the presence of specific defensive substances. I have noted that the patients whom I have treated (I usually employ an emulsion) usually show an increased tendency to local reaction as their disease im- proves. Some patients, however, make a perfectly satisfactory improvement and do not show these local reactions. There are many things to be considered in interpreting tuber- culin reactions. Sometimes the tuberculin is absorbed and car- ried off readily. Under such circumstances we would not expect to have a strong local reaction. At other times, it will remain in the tissues and meet the specific enzymes which are prepared for its destruction, producing a local reaction, which is more or less marked. If the tuberculin reaction is an antigen-antibody reaction, whether it be local, or focal, then it must be taken as evidence of the presence of a specific defense. It must not be considered, however, that the patient who shows this specific de- fense will necessarily get well of his tuberculosis. This depends very much upon the future course of the disease, as well as upon the way the case is handled. Such defense may change from day to day, from week to week, or from month to month; con- sequently, it is very difficult to discuss this question as an ab- stract proposition. It must be considered only at the time of its exhibition, and must be expected to change as the disease pro- gresses. 636 PROGNOSIS NON-TUBERCULOUS COMPLICATIONS. Non-tuberculous complications may arise on the part of any organ or structure. The ones which require particular con- sideration, however, are those which confine themselves to the four great systems of the body, the nervous, respiratory, circula- tory, and digestive. Nervous System. — On the part of the nervous system we have numerous complications which bear upon prognosis. Nearly all patients who suffer from tuberculous toxemia have disturbances on the part of the cells of the central nervous system. This re- sults in more or less depression of nerve tone. Neurasthenia is a very common complication of tuberculosis; in fact, nearly all patients have it to some degree. It influences prognosis to the extent that the neurasthenic symptoms are permitted to inter- fere with the patient's metabolic activity. A neurasthenia of mild degree does not seem to have a particularly antagonistic ef- fect; while, in some cases, a severe degree may have an influence in making the prognosis unfavorable secondary only to the tu- berculous process itself. All of the depressive nervous states produce a general inhibition of the functions of the internal vis- cera and in this way influence prognosis unfavorably. Not only do we have a general loss of nerve tone designated as neurasthenia, but we have an actual degeneration of nerve cells as a result of the tuberculous toxemia. This is sometimes sufficiently extensive to produce definite organic changes in the cells of the central nervous system. This is not infrequently found postmortem in subjects who have had a prolonged toxemia. Aside from these disturbances we have the effect of the tuber- cle toxins influencing the vegetative nervous system and pro- ducing changes in the function of the internal viscera. Inas- much as the nervous system largely controls cellular activity, being supplemented so far as we know, only by the chemical con- trol which comes from the various internal secretions, we can see how important a factor in prognosis the nervous system be- comes. The Respiratory System. — In our discussion we are speaking NON-TUBERCULOUS COMPLICATIONS 637 mainly of pulmonary tuberculosis. Aside from the lesion in the lung or larynx, should there be a complication on the part of that organ, we have other disturbances in the respiratory tract of a non-tuberculous nature which affect prognosis. We might mention the bronchitis which is often present, and the malforma- tions of the upper air passages, as well as the acute infections, such as influenza and pneumonia, which commonly occur during the process of the disease. All of these affect the prognosis to a certain extent. There is considerable discussion whether or not the patient should be operated upon for conditions which interfere with normal nasal respiration, during the time that he is suffering from active tuberculosis. Personally, I have always avoided operations during active disease, and feel that it is better to spare the patient the lowering of vitality which might follow the operation. The after-effect, however, should normal respiration be restored, might overcome any deleterious influences of the operation itself. I would not counsel operation, however, during periods of activity, but confine it to the times when the disease is quiescent. An attack of influenza superimposed upon tuberculosis is of- ten disastrous. In many instances, the death of the patient can be traced to a severe attack of this disease. Pneumonia also oftentimes proves serious for the tuberculous patient; at the same time, I have seen patients with a widespread tubercu- losis go through attacks of influenza and pneumonia without apparent harm resulting. The Digestive System. — The non-tuberculous complications on the part of the digestive system have a very important bear- ing upon the prognosis in tuberculosis. Good nutrition is es- sential to cure. The tuberculous patient is particularly prone to have disturbances on the part of the gastrointestinal tract, as described in Chapter X. The outcome of the case will often depend upon the success with which these complications are handled. Sometimes what appears to be a very serious inter- ference with digestion may be overcome by proper treatment and in this way an unfavorable prognosis be averted. The clinician should always bear in mind the influences which 638 PROGNOSIS are operating to interfere with the function of the gastroin- testinal tract. Toxemia always tends to decrease the gastro- intestinal secretions, as well as interfere with the motor func- tion of the stomach and gut; consequently, toxemia should be relieved as quickly as possible. Depression has the same effect upon the gastrointestinal tract. This should be relieved by put- ting the patient in the proper frame of mind. There are reflex symptoms on the part of the stomach and intestines which re- sult from the inflammation in the lung. These may have a tendency to cause a hyper- or hypo-secretion of either the stomach or intestinal glands. They may also have a tendency to increase or decrease motility in both the stomach and intestines. By careful analysis, the exact condition may be arrived at and the disturbance be corrected. While the tuberculous patient may have gastric ulcer, duodenal ulcer, colitis, appendicitis, or any other complication which affects the gastrointestinal canal, yet the majority of disturbances on the part of the digestive tract are of a functional nature and come through disturbed equi- librium on the part of the vegetative nervous system. The Circulatory System is greatly disturbed in tuberculosis, as mentioned in Chapter IX. A deficient inspiratory act inter- feres with the normal balance between the arterial and venous system, causing a storing up of blood in the veins, particularly in those of the splanchnic area, and a relative decrease in the amount contained in the arteries. Because of the disease in the lung, many vessels are obliterated, and the right heart finds it- self compelled to work against an ever increasing pressure. As a result of this, hypertrophy of the right ventricle eventually takes place. As a result of toxemia and malnutrition, the en- tire body cells degenerate as the disease progresses. The heart muscle itself becomes less able to do its work and atrophies. The final result obtained in tuberculosis depends largely upon the integrity of the heart. In those cases where an arrestment of the disease has been obtained, which is accompanied by wide- spread fibrosis, the patient, as a rule, lives as long as the heart will stand the strain. The patient with an advanced destructive lesion is, as a rule, living on the reserve energy of the heart; consequently, it is unable to measure up to increased demands NON-TUBERCULOUS COMPLICATIONS 639 made upon it. The prognosis in tuberculosis depends very much upon the heart muscle and the proper movement of the blood; for upon these depend the ultimate metabolic activities of the body. Urine. — The urine during tuberculosis shows several important variations from the normal. If the kidney is involved in the tuberculous process, we are apt to have at first a polyuria; and if the calyx is involved, this is usually followed by pus, and blood appearing later. Where an amyloid degeneration of the kidney takes place it is not uncommon to find albumin. Amyloid de- generation is a disease which affects the blood vessels and is usually progressive. There may at first be a small area involved which permits of the escape of albumin into the urine. As the process extends, the blood vessels involved become destroyed and the urine may lose all traces of albumin for a time. It may be free over a prolonged period until the process, becoming more extensive, causes a continuous albuminuria. This being a waxy degeneration of the blood vessels, and usually being associated with the same process in other internal viscera, usually offers a bad prognosis. It means a progressive pathology which will, sooner or later, lead to the death of the patient. The Diazo and Urochromogen Reactions. — These reactions fre- quently make their appearance in the urine, particularly in ad- vanced patients, who are progressively losing ground. These re- actions, if continuous over several months, as a rule, suggest a bad prognosis. Tuberculous patients often, however, will have these reactions appear during an acute illness. Under such con- ditions they disappear as soon as the acute illness is over, and are not prognostically bad. When these reactions come, how- ever, and persist for several months, the chances of the patient's body cells ever being able to carry on their normal physiological function again is highly improbable. (See Chapter XX, page 569.) Blood in Tuberculosis. — The condition of the blood in tubercu- losis has prognostic significance. It is self-evident that the blood which is nearest normal in its constituent parts, functionates the most perfectly. Inasmuch as the blood is the carrier of oxygen and food to the cells, and of the broken-down products to the ex- cretory organs, the necessity of preserving its normal carrying 640 PROGNOSIS power is self-evident. This is particularly true in tuberculosis, because we have so many other factors which also go to interfere with metabolic activity. The circulatory system is disturbed so that the blood does not circulate freely and normally. We have interference with the normal oxygenation of the blood. We also have degeneration in the various cells of the body so that they are not able to functionate normally, even though the blood is able to supply their needs and relieve them of their effete prod- ucts with its usual efficiency. From this it will be seen that the condition of the blood has a very important prognostic bear- ing in tuberculosis, and it should be our endeavor to keep its standard as high as possible. Pregnancy. — Pregnancy influences prognosis in clinical tuber- culosis unfavorably. Many years ago it was noted that certain patients suffering from clinical tuberculosis improved during the pregnant term, and it was not uncommon for physicians to ad- vise tuberculous women to become pregnant as a therapeutic measure. This observation, however, like many others in med- icine, was not complete. While some women improved during pregnancy, many became more seriously ill and many of those who showed improvement during the term lost all that they had gained and suffered from a more active disease after delivery. I look upon pregnancy as being one of the most serious compli- cations in active tuberculosis. The extra burden upon the pa- tient during the period of gestation usually results in reducing her vitality and permitting the disease to extend. Then, the strain of delivery, and the extra cares and burdens which re- sult in the care of the child, are almost sure to bring about in- creased activity of the disease. The question of whether a woman who has suffered from ac- tive tuberculosis may safely bear a child is one that must be care- fully considered. This question cannot be answered in the ab- stract, but conditions in each individual case must be carefully considered. A woman of the middle, or well-to-do classes, who could be properly cared for during gestation, delivery, and af- ter delivery, would be running less risk than the poor woman who could not have such care. As a rule, I advise tuberculous women who have suffered from an early active tuberculosis, that CHARACTER OF TREATMENT 641 it is unwise to bear children until they have been well for a period of at least two years. If they have not shown any active symptoms for two years' time, and, providing they can have the proper care and attention, I then feel that the danger of child bearing is comparatively slight. The burden of childbirth is often less than the mental effect of feeling that they are not able to bear children. The danger of lighting up a process which has been quiescent is relatively greater in proportion to the severity of the disease. Many advanced and far advanced cases, under no circumstances, should be advised or permitted to undergo the strain of childbirth. The question arises, should a woman suffering from active tuberculosis, or one who has recently secured an arrestment, be- come pregnant, what is the proper course for her safety? This is another question that must be considered individually. In many cases it is wiser to interrupt the course of pregnancy, if it is diagnosed early. Other cases may be properly cared for and the pregnancy be allowed to continue. Under all such cir- cumstances, however, if the pregnancy is allowed to continue the patient must receive careful attention, and must not be al- lowed to go through a long strenuous delivery, and must be given every care possible following the birth of the child. PROGNOSIS DEPENDS ON CHARACTER OF TREATMENT. Prognosis From the Standpoint of the Physician. — The prog- nosis in a given case of tuberculosis depends very much upon the physician who treats the case. This is a disease which has a tendency to heal; but, at the same time, in a large majority of cases, after it becomes a clinical entity, it has a tendency to grow progressively worse. Whether or not it shall be checked in its course of advancement depends very much upon the in- telligence with which the treatment is directed. All things else being equal, the man who understands tuberculosis best should be able to handle the case most successfully. In practice, how- ever, it does not always work out in this way because we are not only dealing with a disease, but we are dealing with an individ- 642 PROGNOSIS ual ; so, the prognosis in tuberculosis, in a given case depends not only upon the physician's knowledge of the disease, but upon his ability to successfully inspire the patient to a whole-hearted co- operation. The physician's responsibility in tuberculosis is greater than in almost any other ordinary disease because, at best, the disease is one which will extend over many months, — often several years, — and, during all this time it is the duty of the physician to guide the patient in such a manner that he is able to preserve his resisting power and keep his defensive forces acting to best advantage. The prognosis will usually depend upon the success with which the physician is able to accomplish this end. Cooperation of the Patient. — No matter how intelligent the physician may be, and no matter how comprehensive and satis- factory his plan of treatment, unless the patient gives a whole- hearted cooperation his chances of recovery from active tuber- culosis are not good. A patient may throw away all chances of recovery by some foolish act; or, he may turn an apparently hopeless prognosis into a favorable one by faithful cooperation. Earliness of Diagnosis and Treatment. — The prognosis of tu- berculosis depends largely upon the earliness of diagnosis and the time when proper treatment is instituted. The pathology of this disease is such that it becomes more complex as the disease advances. In the beginning, when the lesion is small, it is not such a difficult thing to prevent the disease from spreading, and keep the patient in the proper environment, both mental and physical, until his lesion is healed. While the lesion is small there is not the same opportunity for bacilli to escape and form metastases that there is later, for the foci are smaller and fewer in numbers than when the disease is extensive. Bacilli escape into adjacent tissues or into the blood stream during the periods when the foci of infection have become necrotic, caseate and break down. The greater the number of caseating tubercles, the greater the danger of such escape of tubercle bacilli, and the greater the demands upon the body to keep infection from oc- curring. Thus, it can be seen that a small lesion does not tax the organism's defensive powers nearly as much as a widespread lesion. No patient ever dies from the original focus, but through CHARACTER OF TREATMENT 643 extensions and repeated extensions. It is to the prevention of these metastases, and secondary metastases that much of our therapeutic endeavor is directed. It is important to heal the lesion which already exists, and to that end we endeavor to raise the resisting power of the patient to the highest point pos- sible, and to stimulate his foci of infection, by specific focal reactions, produced either by tubercle protein from his own tu- bercles, or by the tubercle protein introduced from without. It is not difficult to see the great importance of treating the lesion while it is small. In this, tuberculosis is no exception to other diseases. It is far better to repair a small damage than to wait until it grows. This is a good rule in all lines of endeavor. Early diagnosis, with proper treatment, in intelligent patients, should bring about an arrestment in at least 90 per cent of cases. After the disease has extended, however, and the early clinical tuberculosis has passed on into the moderately advanced stage, the prognosis has been reduced from 90 per cent to 50 or 60 per cent. The time required for this decline in prognosis to occur may be short or it may be long. Very often we see an early lesion change to one of moderately advanced activity within a period of a few weeks. Time is the essential factor in tuberculosis. The time of the diagnosis, the time when treatment is begun, and the length of the time that the treatment is carried out are factors of the greatest importance. Advanced tuberculosis, while not hopeless, as was formerly thought, proves to be very difficult to control. If we take the ordinary advanced cases of tuberculosis as they come to us, the chances of bringing about a healing are not very good. We can produce a healing, under ideal conditions, in about 10 per cent and an arrestment in about 30 per cent more, if we include both active and quiescent cases that come under our care. If we exercise care in choosing cases, and take only those which are more hopeful, we can bring about an arrestment in a very much larger percentage. On the other hand, if we confine our endeav- ors to those who are suffering from active advanced disease, with more or less constant toxemia, the percentage will be greatly re- duced. 644 PROGNOSIS If the medical profession could only learn the importance of early diagnosis and the immediate treatment of tuberculosis, it would not take long to satisfy the most skeptical that tubercu- losis is a curable disease even with our present indirect methods of treatment. If, on the other hand, we are to continue to spend our efforts trying to repair lungs which have been de- stroyed by the tuberculous process, and continue our attempts to restore the organism to a condition of efficiency, after this disease has become widespread, both laymen and physicians will continue to feel pessimistic regarding its prognosis. Character of Treatment. — The prognosis depends very much upon the character of the treatment. Some patients get well without undergoing any definite course of treatment, even with- out knowing that they have had clinical tuberculosis. Most patients, however, when the active disease has made its appear- ance, require some form of active assistance if they are to re- cover their health. Tuberculosis requires a carefully planned therapy. This is particularly true because we have no definite, direct method of attacking it. Until we can find some specific remedy, like quinine in malaria, or salvarsan and mercury in syphilis, which will directly attack the tubercle bacillus and produce its destruction, we must work on in an indirect way. It is necessary at the present time, to deal largely with the pa- tient's resisting power. While this is an indefinite and uncer- tain quantity, yet, with our recent advances in knowledge, it is becoming a more tangible asset. We must build up his nutri- tion; keep his metabolic activities at the highest point possible; aim to preserve his nervous equilibrium; a healthy gastroin- testinal activity, and an efficient circulatory balance. This can only be done by carefully studying the patient as an individual and suiting the various remedies and measures which are at our command to his needs. The only remedy we have, which has any specific action, is that derived from the tubercle bacillus itself. Preparations made from the bacillus are specific in that they produce protective sub- stances against those portions of the bacillus contained within them and in that they react when they come in contact with the specific proteolytic enzymes which the body cells are stimulated CHARACTER OF TREATMENT 645 to produce; and also in that such a reaction, if it occurs in and near the focus of infection, stimulates the production of fibrosis and healing. The utilization of these remedial measures for the best in- terests of the patient is not easy. Many of them seem so simple that this fact alone defeats their proper employment. I am a firm believer in the intensive treatment of tuberculosis. Success depends upon an intimate relationship between the pa- tient and physician and their thorough cooperation. This asso- ciation must continue over a prolonged period of time; and the various helpful measures must be adapted to the patient's par- ticular needs as they change from time to time. Such treatment, when carried out with a whole-hearted cooperation on the part of the patient, makes the prognosis in tuberculosis quite favor- able. It has been able to produce an arrestment in more than 90 per cent of early clinical tuberculosis; more than 60 per cent of moderately advanced cases ; and more than 30 per cent of far advanced cases. The let-alone policy, which is carried out far too commonly, will reduce the percentages above mentioned, by 50 per cent. It is far more sensible to let a patient carry out a let-alone policy with typhoid fever, pneumonia, scarlet fever, and other acute infections, which run a short course, than it is to carry out such a policy with tuberculosis. The results would be no more disastrous than they have been, and still are, in tu- berculosis, when such a course is followed. In this long drawn- out disease, which depends so much for favorable results upon a prolonged and hearty cooperation, close medical supervision with an intensive routine is an important factor in prognosis. Sanatorium Versus Home Treatment. — When the diagnosis of tuberculosis is made the most important question to decide is whether the patient is to be treated in the home or in some sana- torium. From the standpoint of prognosis, there is no question as to which course should be pursued. From the standpoint of expediency, however, at times, it may be necessary to follow a course which offers less chances of cure. All else being equal, and granting that the patient is being treated by a physician with equal skill, whether it is in the home or in the institution, and that the institution is run in such a manner as to give the 646 PROGNOSIS patient the benefits which such an institution should provide, there is no comparison in the two methods from the standpoint of prognosis. A properly conducted sanatorium furnishes an ideal place for the application of the measures which are best and most useful in the treatment of tuberculosis. It removes the patient from the home with its cares and worries; relieves him from contact with business and its troublesome details; and places him in an atmosphere of helpfulness and hopefulness, where he has an op- portunity to associate intimately with trained physicians and attendants, all of which has a tendency to improve his chances of cure. In the home, on the other hand, the difficulties are many, and oftentimes unsurmountable. Home cares; home worries; a fail- ure to keep up the proper program; the attempt to make the home, which was intended for the well, a place for the sick, while it, at the same time, is being inhabited by those who are well; and the association with those who are interested and engaged in the usual activities of life, make it almost impossible for the patient to keep up a cooperation sufficiently long for the disease to become arrested, or healed. When I have placed my patient in the sanatorium, I feel that his chances of recovery have in- creased from 25 to 50 per cent (See Volume II, Chapters XL VII and XLVIII.) Open Air. — Open air as a curative measure in tuberculosis is universally recognized, and rightly so; because there is no other single factor, which is so generally applicable and which is cap- able of giving the patient equal aid. Patients can get well of tu- berculosis without being treated in the open; but, when we realize that the great value in the air is the physical effect which it exerts upon the body, the value of treating a patient in the open air, as compared with treating him in rooms, particularly in closed rooms, is self-evident. It is desirable that those who are treating tuberculosis should know the limitations of open air therapy, and realize that it is only one of many measures for the improvement of the patient's general resisting power; at the same time, they should fully realize that its intelligent application materially increases the CHARACTER OF TREATMENT 647 patient's chances of cure. When weather and climatic condi- tions are favorable, open air should always be employed. While it is possible to treat patients under conditions where the full benefit of open air cannot be satisfactorily obtained, it is all the more necessary under such circumstances to bring to the aid of the patient other measures which influence metabolism, such as psychotherapy, hydrotherapy, good food, and rest. Open air, as I have described more fully in Volume II, Chapter XXXVI, im- proves the nutrition of the skin, stimulates the superficial nerve endings, and, through them, influences the cellular activity of the internal viscera. The reaction which ensues facilitates gas- eous exchanges and favors the maintenance of heat equilibrium; thus producing a beneficial influence upon the entire metabolic activity of the organism. Climate. — Not many years ago climate was considered to be the main factor in the treatment of tuberculosis. It was thought that if a patient could live under certain climatic influences, that his chances of cure would be good; and, further, that if he could not obtain such climatic change, little could be expected. For a time it was thought that these favorable climatic condi- tions were found only in the high mountains. This idea was based on an article published in the Edinburgh Journal in 1848 by Archibald Smith, who visited the Andes and noted that, while tuberculosis was extremely common at Quito, there was very little in the mountains above this city; consequently, he came to the conclusion that there was an immune zone somewhere be- tween the altitude of Quito and the small cities of the moun- tains. This observation was confirmed in other high mountain resorts. It was seen that while there was much tuberculosis in the large cities of Germany and France, there was little in the high altitudes; while there was much tuberculosis in our east- ern cities, there was little in the Rockies; consequently, it was accepted as a fact that treatment at high altitude offered the best chances of cure. Further observation, shows that there is no zone immune to tuberculosis. Tuberculosis exists in all sections of the globe, and under all climatic conditions. It is most prevalent where people mass together, being particularly common in cities. It is 648 PROGNOSIS an economic and social disease. In the sparsely settled districts, whether they be at an elevation, or at sea level, or even below sea level, as in our own Salton Desert, and the Steppes of Russia, there is very little tuberculosis. Tuberculosis can, and will, de- velop anywhere. People are infected in childhood. They carry the bacilli in their tissues as they grow older; and, if conditions are brought about, which tend to lower their resisting power, the bacilli may spread, multiply, and produce clinical tuberculosis. Such alterations in defensive powers are less apt to occur where hygienic conditions are maintained and where people live lives conducive to strength, as they do in country districts. We must not forget the influences exerted upon the body metabolism by sunlight and humidity and other physical principles. There is no question that conditions more favorable to metabolism are found in climates which favor an out-of-door life, which have a large percentage of sunshine and low humidity, as compared with areas where dampness and cloud prevail. A country which in- vites the patient to be out of doors, and which offers physical surroundings in the way of natural scenery and vegetation which are pleasing to the physical sense, will undoubtedly improve the patient's chances of recovery (see Volume II, Chapter XXXVII). Heliotherapy. — Heliotherapy adds to the patient's chances of cure. In superficial lesions, particularly those accompanied by ulceration, the curative influence of sunlight is quite marvelous. Many ulcerations which, formerly, proved very difficult to handle, by long tried surgical methods, have yielded quite readily to modern sun and air treatment. While these may be aided to a certain extent by exposure to the air, exposure to sunlight seems to have an added curative influence. The effect of sunlight, however, is not confined to its influ- ence on local lesions. The influence which it has upon metabol- ism, through its stimulating effect upon the surface of the body, is an important factor. We must not lose sight of the fact that a very important effect in heliotherapy may be its influence upon the blood which circulates through the superficial capillaries. Heliotherapy should be employed as an important physical meas- ure in building up the patient and improving his general resist- ing power. Unfortunately, it can be used only to a limited ex- CHARACTER OF TREATMENT 649 tent in some climates; but, wherever the sun shines, heliotherapy can be utilized to some extent, although not to its fullest ad- vantage (see Volume II, Chapter XLIII). Hydrotherapy. — This is a measure which can be used in any climate and adapted to all conditions, providing the physician understands the physiological effects of water. I have never seen a patient to whom baths could not be advantageously adjusted. Much of the failure in the application of hydrotherapy has been due to the fact that the use of water seems so simple. When one realizes, however, that the condition of the patient, the pres- ence or absence of toxemia, the condition of his superficial blood vessels, the state of his metabolic activity, the condition of the atmosphere which surrounds him, the temperature of the water, the mechanical impact of the same, and the use or non-use of fric- tion during and after its application, are all variables which enter into the effect produced, one can see that attention to detail in its application is absolutely essential to success. When adapted to the needs of the individual, however, we have in hydrotherapy a very useful measure for improving the patient's metabolic ac- tivity and increasing his power to overcome disease (see Chapter XLII). Food. — The prognosis in tuberculosis depends upon a sufficient dietary. No matter what other measures are employed, a suf- ficient amount of food must be used by the patient if he is to regain health. While he may go through periods when the amount of food eaten is not sufficient to supply the demands of his body, yet, if these are long continued, malnutrition will fol- low, which greatly interferes with the patient's chances of cure. There has been much discussion about what constitutes an adequate dietary. There is no unanimity of opinion as to what dietary is the most useful for the tuberculous patient; at the same time, all agree that the patient should be supplied with a sufficient number of calories to take care of his ordinary meta- bolic changes, plus the extra demands which are made upon him by his disease, and still have a surplus for increasing his defen- sive powers. Some observers favor a diet rich in fats; others rich in protein; and, occasionally, we find someone who believes that extra large amounts of carbohydrates should be employed. 650 PROGNOSIS Suffice it to say, that our digestive capabilities are such that when reinforced by the metabolic activities of the cells, we are able to derive sufficient nutriment from dietaries which are not formed according to our scientific ideas. A patient can nourish him- self on foods which are largely carbohydrate, largely protein, or largely fat; at the same time, it is undoubtedly wise to supply the body with foods belonging to each of these classes in quan- tities which experiments have shown to be the most rational. From the prognostic standpoint, nutrition is the goal to be aimed at, not fat. Nothing is gained, however, by putting on weight if it is necessary, in order to do so, to give the patient large quantities of food over a prolonged period of time. Over- feeding is still too commonly found in the treatment of this dis- ease. The patient is led to believe that if only he can keep fat he will get well. Fat is, prognostically, bad rather than good. The fat patient is soft, not resistant. He has too much extra tissue to care for, without having a corresponding increase in strength and vigor (see Volume II, Chapter XXXIX). Rest and Exercise. — The prognostic influence of rest is recog- nized by all students of phthisiotherapy. In the writer's personal experience, he has gradually learned to have great respect for the influence of these two measures when properly applied. I am sure, as I look back on some of the results in my early prac- tice, that many failures could have been prevented had I fully realized the importance of rest in treatment. A patient's chances of recovery are increased greatly if he is confined to bed during the entire period of not only clinical activity, as expressed in the symptoms which accompany toxemia, but also during the period when there are widespread lesions in the lung, accom- panied by signs and symptoms, which indicate that the patho- logical changes are still taking place rapidly. I am inclined now to keep my patients at rest until I feel reasonably certain that there is no further danger of necrosis and caseation taking place. While it is difficult to assign to the various measures which we employ their true part in the production of a favorable result, yet I am sure that I cannot emphasize too strongly the prog- nostic importance of rest during the early months of treatment of all patients who are suffering from tuberculosis, CHARACTER OF TREATMENT 651 Exercise is likewise a valuable adjunct and adds greatly to the chances of cure by improving the patient's metabolism and making him strong and more resistant. It does this, however, only when it is nicely adjusted to the individual patient's par- ticular pathology. If one is to err in prescribing either rest or ex- ercise, let it be on the side of rest (Volume II, Chapter XXXVIII) . Psychotherapy. — As mentioned elsewhere in this monograph, one of the factors which is capable of doing most good in the treatment of tuberculosis is psychotherapy. If employed to its fullest value, it can even make up some of the deficiencies which come from a failure to fully utilize other measures. I have often said that I would rather have a patient treated in a room, if I could give him the benefit of hydrotherapy and psychother- apy, with good food, than treat him in the open air, with hy- drotherapy and psychotherapy omitted. The contentment and cooperation of the patient is such an important factor that I can- not emphasize too strongly the importance of this measure in the treatment of tuberculosis. The effect of this measure is illus- trated by an incident which came under the writer's notice re- cently. Two physicians were treating the same group of pa- tients, — one of whom had a strong personality and used psycho- therapy to its full value, while the other lacked magnetism and was more or less mechanical in his methods. A patient was going to the office for treatment and was sometimes treated by one and sometimes by the other. One day the patient remarked to the physician first described: "I do not know why it is; you and your associate use the same measures, and both give tuberculin in the same manner, but when I leave your associate I feel that I have had nothing but the injection. When I leave you I feel happy, contented, and relieved of all apprehension for the day." This experience is not an uncommon one. Personality is a great factor in medicine. All physicians who are desiring to be suc- cessful in the treatment of a chronic disease like tuberculosis should cultivate cheerfulness, optimism, friendliness and sym- pathy, that they may give their patients not only the benefit of the usual physical measures, but also the full physiological benefit that comes from a helpful psychic attitude (see Volume II, Chap- ter XLI). 652 PROGNOSIS Tuberculin. — Of all the remedies used in tuberculosis, tuber- culin is the only one that has a direct specific influence upon the tuberculous tissue. Tuberculin is employed in the treatment of tuberculosis for two distinct purposes; one, that of producing immunity against the products of the tubercle bacillus; the other, that of producing a focal reaction which stimulates the pro- duction of fibrosis. It was formerly thought that the production of immunity was the chief function of tuberculin ; but, as we study its action more and more, this seems to be open to question. There is no doubt that any foreign protein will produce an immunity against itself, so that the various components of the tubercle bacillus, which are found in the individual preparation of tuberculin em- ployed must, of necessity, establish a resistance on the part of the body cells against themselves; and there is further no doubt that this has considerable influence in keeping up a specific re- sistance against the tubercle bacillus; but in most cases of tu- berculosis, resistance to the bacillus is already high, and an increased immunity is not so important. The patient constantly gives himself doses of bacillary products from his own focus; and, in this way, gets the identical stimulation which is essential to the production of a full immunity against the bacillus. As far as we know, we are not able to obtain this regularly by any preparation of tuberculin that we have hitherto employed. Any specific product made from the tubercle bacillus, how- ever, possesses the peculiar properties of producing a reaction between itself or the products which result from its chemical decomposition, and the body cells. When this reaction occurs in, and near the focus of infection, it produces a stimulation, which results in hyperemia or congestion, which hastens healing. When tuberculin is intelligently employed it favorably in- fluences prognosis. It is as difficult to estimate fully the value of tuberculin in the treatment of tuberculosis as it is to estimate the value of fresh air, good food, psychotherapy, and climatic conditions; because when tuberculin is used, many of the other measures are likewise employed. After twenty years' experience in the use of tuberculin, I have no hesitancy in saying that this remedy, when properly suited to the individual patient under CHARACTER OF TREATMENT 653 treatment, and not given haphazardly, or by routine, will add at least a minimum of 20 per cent to the chances of healing. I further believe that, if carried out sufficiently long the tuber- culin treatment will unquestionably produce a firmer scar and more complete healing. It is my observation that those patients who have been successfully treated with tuberculin and in whom the treatment has been kept up for a sufficient length of time, show less tendency to relapse than those who are treated by the usual dietetic, hygienic measures alone. Tuberculin is not a remedy that can be used to best advantage by men who are unaccustomed to its use ; consequently, its favor- able influence will have to be denied to a large percentage of those who are suffering from this disease. The value of this remedy has been recognized for a long time by those who are ordinarily opposed to its general use, in those cases which have failed to make satisfactory progress with- out its employment. They justify its use in such cases by saying that it seems to furnish the stimulation necessary to start these cases, which have hitherto failed to respond to ordinary measures, on the road to recovery. If of value in these cases, it stands to reason that it must be of value in others, although its influence might not be so apparent in those which show a general tendency to- ward healing without it. When one bears in mind, however, that any healing that occurs in tuberculosis takes place because of the specific focal stimulation produced by the products of the tubercle bacillus, the rationale of this remedy is evident (see Volume II, Chapter XL). Induced Pneumothorax. — During the past decade induced pneumothorax has been gradually gaining supporters among those who are interested in the cure of tuberculosis. The theory on which its employment rests is that it puts the diseased organ at rest; compresses the areas of activity and necrosis; prevents the absorption of toxins ; and, by so doing, relieves the patient of the debilitating action of toxins and enables him the better to build up his defensive powers. Induced pneumothorax is sup- posed to be applicable only to one-sided lesions, although it has been tried by some during more recent times, where both lungs were involved, compressing one side at a time. 654 PROGNOSIS That pulmonary compression at times aids in the enre of tu- berculosis cannot be denied, and there is no doubt in my mind but that many men will give their patients better chances of cure by putting the lung at rest, and filling the pleural sac with gas than they would by not doing so. On the other hand, the percentage of cases where it is essential to cure, from my observation, are very few. The cure of tuberculosis, even when induced pneumothorax is used, does not consist alone in filling the pleural sac with gas. This must be kept filled, and the patient must be cared for and treated the same as when this is not used. Its final effects must also be considered. There are a certain number of accidents which attend its employment, such as pleural shock, rupture of a cavity wall, pyopneumothorax, and causing the disease to become more active in the other lung. The after-effects must also be considered. From the physiological standpoint it is impossible to compress the entire lung over a pro- longed period of time, without producing a severe strain upon the heart. There is considerable question whether at the end of the period of a few months or a year or more, that is necessary to produce a result by this measure, the heart will not have been subjected to a strain which will eventually prove to be the patient's undoing. The ordinary hygienic treatment, with proper psychotherapeutic influences and tuberculin added, under ideal conditions, is probably more satisfactory and more rational in the handling of the disease than is induced pneumo- thorax ; nevertheless, there are many patients who for one reason or another, cannot be given these other measures to best ad- vantage for whom induced pneumothorax, with other helpful measures that can be employed, will offer better chances of cure than though it were omitted. In estimating the value of this measure one must bear in mind that it is good lung tissue which collapses first; consequently, if full value is to be obtained from its employment, the compression must be complete (see Volume II, Chapter XLIV.) Pharmacological Remedies. — Pharmacological remedies, now and then, have a very important influence in the treatment of tuberculosis. There are certain remedies which are of great value in improving the symptoms and complications which exist, CHARACTER OF TREATMENT 655 and without which it would be very difficult to treat the patient successfully. Among such may be mentioned the various forms of opium used for pain and cough; atropin to combat many of the vagotonic conditions; hydrochloric acid, in cases of deficient gastric secretion; laxatives which, of course, should be reduced to the minimum, the condition of the bowels being controlled as largely as possible by dietary and other measures; sedatives, other than opiates, such as the bromides, for the relief of nervous- ness; remedies for sleep, when this cannot be induced by other measures; and last, but not least, we must not forget such preparations as digitalis, strychnine, iron and arsenic, which can often be used to the advantage of the patient. In speaking of the prognostic value of pharmacological remedies we must bear in mind that the relief of troublesome symptoms is often of inestimable value to the patient. Some symptoms, such as pain and sleeplessness, while, in themselves, not so dangerous, produce certain impressions upon the nerve cells which result in depression and general interference with cellular activity; so, we cannot ignore the importance of these common symptoms in their effect upon the prognosis in tuber- culosis. We can favorably influence prognosis by relieving nagging, distressing symptoms and complications; so, we must not neglect the little things that add comfort and make for con- tentment and happiness during the long period necessary for cure (see Volume II, Chapter XL VI). Change of Occupation. — Much foolish advice is often given to patients suffering from tuberculosis, or who have recently ob- tained an arrestment of their disease. Probably no advice is given more readily than that of telling the patient to change his occupation, — to get out in the open air. Such advice should not be given so readily; and during recent years, instead of advising my patients to change their occupation, and get out in the coun- try, I have been looking upon the matter from what I believe is a more sensible standpoint. The occupation followed by the pa- tient, as a rule, occupies about one-third of his time. It is not so much what the patient does during the one-third of the time as it is the other two-thirds of his time that determines whether or not he is to regain his health. 656 PROGNOSIS Oftentimes patients are told to go to the country and take up some new work, for which they are totally unfitted by nature, and are often unable to do financially. The result is that the pa- tient obtains the fresh air but is compelled to learn a new oc- cupation and to make financial sacrifices which greatly reduce his comfort, and interfere with his state of health. It is more sen- sible when a patient consults a physician as to his occupation, to find out whether or not he does his work easily, whether he knows the work that he has been doing; and if he does it easily, tell him to continue it, but to look well to the other two-thirds of the twenty-four hours which remain after his work is done. If he will give himself proper rest, see that he has substantial food, sleep out of doors, and avoid excess, the eight hours of work in the office, or mill, or shop, as a rule, will be no more harmful to him than undertaking to master a new work, or new profession for which he has no particular aptitude and which causes an entire rearrangement of his life and habits, even though the latter is in the open. This fact is better understood now that we know that it is not the lack of oxygen in the inside air that proves harmful (see Volume II, Chapter XXXVI). INDEX Abscess, pulmonary, case illustrating, ii. 585 symptoms of, ii. 585 Aching, general, part of syndrome of toxemia, ii. 110 Acidosis in tuberculosis, i. 456 produced by deficiency in oxygen, ii. 281 Acromion process in advanced tuber- culosis, i. 471 Actinomycosis, differentiated from tu- berculosis, i. 620 Activity, clinical, no evidence of, in percussion, i. 426 meaning of, ii. 549 waves of, common in advanced tu- berculosis, ii. 575 Adolescence and tuberculosis, i. 109 period of low resistance, ii. 199 Adrenal gland, developmentally a part of sympathetic system, i. 173 part of chromaffin system, i. 173 Adrenals, stimulated when sympathet- ica stimulated, i. 219 Adrenin, action of, i. 219 in prolonging toxic symptoms, i. 605 acts at myoneural junction, i. 173 in treatment of asthma, ii. 167 Adults, danger of being infected from without, i. 89 early clinical tuberculosis in, ii. 506 open tuberculosis in, ii. 509 Aeby, description of growth of lung, i. 127 Aerogenous infection, i. 65 difficulties of, i. 67 Age periods, statistics of, healing, i. 97 mortality, i. 97, 98 tuberculosis differs in different, i. 96 Air, beneficial effects of, due to phys- ical properties and mechan- ical action, ii. 231 city vs. country, ii. 264 Air— Cont 'd cold, effect of, depends on reactive powers of patient, ii. 272 vs. warm, ii. 271 confined, favors infection, ii. 246 deleterious effect of carbon dioxide, not proved, ii. 230 diathermacy of, increased at alti- tude, ii. 270 effects of, produced on nerve end- ings of skin, ii. 271 expired, organic poison in, ii. 234 inside and outside, differ, ii. 245 lack of motion in, produces heat stagnation, ii. 235 movement of, diminished in city compared with country, ii. 264 movement of, influence on body, ii. 236, 243, 258 open (see Open air) stale, deleterious effects of, ii. 231 supposed diminution of oxygen in, ii. 232 supposed effect of excess of carbon dioxide in, ii. 233 Air baths in fever, ii. 455 Air-borne disease differs from blood- borne, i. 33, 67 Air cells in different parts of lung ex- pand unequally, i. 145 Albers-Schonberg, cause of trunk shadows in lung plate, i. 522 Albrecht, E., and H., and primary lung focus, i. 66 Albumin reaction in sputum, diag- nostic value of, i. 538, 582 Alcohol bath should not be used, ii. 412 Alimentary infection, i. 69 Altitude, changes in blood at, ii. 259 formerly thought to be necessary, i. 647 Alvarez, studies on motility of intes- tinal canal, ii. 40 Amyloid degeneration, i. 43 in gastrointestinal tract, i. 280 Anaphylaxis, ii. 157, 158 658 INDEX Anaphylaxis, and asthma, ii. 157, 161 and hay fever, ii. 157, 161 and shell fish poisoning, ii. 157, 161 and toxemia contrasted, ii. 158, 341 and tuberculin reaction, ii. 162 and vegetative nervous system, ii. 157 bladder in, ii. 160 blotching of skin in, ii. 160 bronchial secretion in, ii. 159 bronchial spasm in, ii. 159 collapse in, ii. 160 diarrhea in, ii. 159 due to peripheral vagus stimulation, ii. 343 fall in temperature in, ii. 160 fatal, central nervous system in, ii. 160 itching of skin in, ii. 160 low blood pressure in, ii. 160 motility of intestinal tract in, ii. 160 nausea in, ii. 159 perspiration in, ii. 160 prevented by atropin, ii. 343 sphincters in, ii. 160 syndrome of, ii. 159 due to central plus vague stimu- lation, ii. 343 urticaria in, ii. 157 vomiting in, ii. 159 Anatomical facts, important in chest examinations, i. 319 Anemia, and early clinical tubercu- losis, i. 364 arterial, cause of, i. 303 following severe hemorrhage, ii. 172 Anergie, cause of metastases, i. 36 Aneurism, cause of large per cent of fatal hemorrhages, ii. 172 Anger, effect on temperature curve, ii. 148 Animals, experiments on, with tuber- culin inconclusive, ii. 333 explanation of immunization of, ii. 334 relation to tuberculin not the same as that of human beings, ii. 334 not easily immunized with tubercu- lin, ii. 333 Antibody, formation of, favored by fever, ii. 118 Antiformin method of examining sputum, i. 556 Antigen-antibody reaction, tuberculin an, i. 503, 513 Apathy toward tuberculosis, cause of, ii. 187 Apex, compression of, follows anatom- ical growth, i. 134 first pulmonary metastases form in, i. 36, 87 hardness of tissues over, denotes disease, i. 415 lessened respiratory motion, predis- poses to infection, i. 38, 134 why involved in adult and not in child, i. 117 to 147 Apical infection and shortened first rib, not parallel, i. 145 Apices, frequency of infection of, in adults, i. Ill, 406, 408, ii. 191 Appendix, tuberculosis of, ii. 40, 653 operation for, ii. 593 Appetite, improved by open air, ii. 248 psychotherapy, ii. 394 • in tuberculosis, i. 255 lack of, part of syndrome of tox- emia, ii. 110 loss of, caused by toxemia, i. 370; ii. 314 Arneth's classification of neutrophiles, i. 577 Arnsperger, cause of trunk shadows in lung plates, i. 522 Arsenic in treatment of tuberculosis, ii. 465 Arteries, small in tuberculosis, i. 46 Arteries, thickening of, in tuberculo- sis, i. 44, 240 withstand necrotic process in tuber- culosis and resist oblitera- tion, ii. 171 Aspergillosis differentiated from tu- berculosis, i. 621 Asthenia, general, and tuberculosis, i. 612 case illustrating, ii. 607 Asthenic type of individual, charac- teristics of, i. 340 Assmann, accuracy and limitations of x-ray, i. 521 shows trunk shadows due to blood vessels, i. 522 Asthma, ii. 164 adrenin in, ii. 167 and anaphylaxis, ii. 157, 161 atropin in, ii. 167 INDEX 659 Asthma — Cont 'd bronchitis a cause of, ii. 164 complicating pulmonary tuberculo- sis, case illustrating, ii. 605 definition of, ii. 166 due to peripheral protein irritation, ii. 166 dust, vapor, and atmospheric con- dition, in cause of, ii. 164 etiology of, ii. 164 occurs in those who have other vago- tonic symptoms, ii. 166, 177 produced reflexly by stimulation of many branches of greater vagus, ii. 165 reflex cause of, ii. 164 relieved by sympathetic stimulation caused by toxemia, ii. 161, 167 symptoms of, ii. 164 due to increased vagus tonus, ii. 167 treatment of, case illustrating, ii. 167, 605 Atmosphere, humidity and tempera- ture of, influence of, on body, ii. 258 Atrophy, regional, as sign of intra- pulmonary disease, i. 412 Atropin in night sweats, ii. 451 spastic constipation, i. 277 treatment of vagotonic condition, ii. 169 Atropin, in treatment of asthma, ii. 167 hyperchlorhydria, i. 261 tuberculous enteritis, case illus- trating, ii. 648 prevents anaphylaxis, ii. 343 Auer and Lewis, studies in anaphy- laxis, ii. 343 Auscultation and abdominal breath- ing, i. 428 Auscultation, difficult in early tuber- culosis, i. 610 early diagnosis should not depend on, i. 427 effects produced on, by changes in soft tissues, ii. 61 ; i. 428, 431 extrapulmonary rales on, i. 482 i factors causing changes in, i. 397 harsh breathing on, i. 479 in advanced tuberculosis, i. 478 in early pulmonary tuberculosis, i. 426; ii. 526 Auscultation — Cont 'd in emphysema, compensatory, i. 495 in extensive fibrosis with necrosis, cases illustrating, ii. 544, 556, 569, 581, 601, 611, 623, 634, 652 in pleura, thickened, i. 497 in pleural effusion, i. 496 in pleurisy, dry, i. 496 in pneumothorax, ii. 81 in pulmonary cavity, i. 491 fibrosis, i. 489 infiltration, i. 488 influence of soft tissues on, in- ferred from their thickness, i. 332 intensity of sounds heard on, de- creased by pressure on steth- oscope, i. 427 interpretation of findings on, i. 433 method of breathing during, i. 428 no sounds heard on, always denot- - ing activity, i. 407 prolonged expiration on, i. 478 rales on, i. 480 rough breathing on, i. 497 should not be made through cloth- ing, i. 427 Austrian and tuberculin reaction, ii. 336 Autoinoculation and exercise, ii. 203 Automobiling not suitable exercise, ii. 300 ! B Bacillary index for estimating rela- tive number of bacilli of dif- ferent lengths, i. 565 Bacillen Emulsion (B. E.) Koch, ii. 356 Bacilli, action of, in producing fever, ii. 122 bunches and free, comparative study of, i. 545 bunches of, broken up by chloro- form and xylol, i. 549 carried by the fly, i. 78 classification according to method of taking stain, i. 542 comparative chances of finding in 1, 2, 5, 10, and 15 minutes search, i. 542 concentration vs. scattering for ex- amination, i. 552, 555 conditions favorable to implanta- tion of, ii. 197 660 INDEX Bacilli— Cont'd course in blood, i. 32 daily variation of, in sputum of low bacillary count, i. 549 danger of from dried sputum, i. 563 death of, favored by sunshine and dryness, ii. 270 difference in behavior of in primary and metastatic infections, i. 84 distribution of, study of, i. 545 distribution of, by mechanical shaker, i. 554 in sputum, i. 540 dosage of inoculation of, ii. 504 enter uninjured mucous mem- branes, i. 30 escape from foci of infection, ii. 331 factors interfering with penetration of stain in, i. 541 gain access to blood stream and produce fever, ii. 156 good technic for examination for, essential, i. 541 grown on one tissue favor same tissue in new infection (Rosenow), i. 32 growth of, checked by fever, ii. 118 implantation of, favored by, i. 37 indirect methods of demonstrating, i. 560 in feces, ii. 513 infection by, and cell sensitization, i. 34 inoculation of, begins soon after birth, ii. 195 in stool of tuberculous, i. 52 in stool in tuberculous enteritis, ii. 41 in tissues without producing his- tological tubercle, i. 65 intertransmissibility of bovine and human, i. 57 life of, favored by cloud and mois- ture, ii. 270 long, in more chronic lesions, i. 592 method of estimating number in 24 hr. specimen, i. 562 finding, when rare, i. 549 morphological classification of, i. 564 multiply when activity present, i. 368 Bacilli— Cont 'd multiplication of means activity, ii. 190 mutation of type of, i. 65 number in sputum, i. 561 once in vessel may infect any or- gan of body, i. 124 pass through glands in childhood, i. 31 penetrate blood vessel walls, i. 124 intestinal wall easily in child- hood, i. 71, 100 pig inoculation to determine, 1. 560 presence and form of, in prognosis, i. 633 secretion from mucous membrane may be contaminated by, i. 563 short, from actively breathing down areas, i. 592 solvents for wax of, i. 548 sputum culture of Petroff, i. 560 staining for, i. 556 tubercle differentiated from smeg- ma, i. 559 virulence of, in fibroid tuberculosis, i. 40 wet method of preparing slides for examination for, i. 556 Bacteria, defense against, i. 218 effect of light on, ii. 418 multiplication of, prevented by fe- ver, i. 373 Baldwin and artificial immunization, ii. 335 Baldwin and tuberculin hypersensi- tiveness, i. 506 reaction, ii. 336 tuberculin reaction and anaphylaxis, ii. 341 Barlow, discussion of climate, ii. 255 Bartel, incubation period in tubercu- losis, i. 65 Bateman discusses food value of raw eggs, ii. 325 Bath, alcohol, should not be used, ii. 412 cleansing, ii. 412 cold sponge, ii. 407 conditions governing, ii. 404 during hemorrhage, ii. 183 effect of, depends on warmth and degree of impact, ii. 402 on temperature, ii. 154 foot, importance of, ii. 412 hot and cold, effects of, ii. 405 INDEX 661 Bath— Cont'd influences all parts of body, ii. 402, 404 neutral, effects of, ii. 405 reaction after, ii. 406 spray, ii. 409 sun, ii. 423 tepid sponge, ii. 410 vinegar, and night sweats, ii. 451 Bayliss, vegetative nervous system and endocrine glands, i. 169 Bechterew, on mediation in sympa- thetic ganglia, i. 191 on the function of nerve centers, i. 169 Bennett establishes children's sea- shore home, ii. 268 Biedl, internal secretions, i. 169 Biedl and Kraus, studies in anaphy- laxis, ii. 343 Biliousness (so-called), i. 277 Bladder, in anaphylaxis, ii. 160 tuberculosis of, ii. 101 Blastomycosis differentiated from tu- berculosis, i. 621 Blood, and lymph flow influenced by stimulation of skin, ii. 402 antibacillary elements of, cause in- fections to be mild, i. 78 Arneth's classification of neutro- philes in, i. 577 bacilli course in, i. 32 changes in, at altitude not evidence of curative influence, ii. 259, 261 at different altitudes, evidence of physiological adaptation, ii. 259 part of syndrome of toxemia, ii. 110 coagulability of, in hemorrhages, ii. 178 concentration of, at altitude, ii. 259 condition of and prognosis, i. 639 diagnostic and prognostic value of findings in, i. 585 effect of light on, ii. 420 examination of, i. 575 from cavity, characteristics of, i. 29 general differential count in, i. 576 occult, in feces, method of examin- ing for, i. 580 technic for procuring specimens, i. 576 time of day for examining, i. 576 Blood-borne diseases differ from air- borne, i. 33 Blood pressure, in tuberculosis, i. 235 low, effect of, i. 237, 238 in anaphylaxis, ii. 160 mechanisms involved, in maintain- ing, i. 236 rise in, in tuberculosis, i. 239 Blood spitting, and early clinical tu- berculosis, i. 364 early sign of tuberculosis, i. 216 makes diagnosis of tuberculosis al- most certain, ii. 170 symptom of early tuberculosis, i. 390 Blood vessel, aneurism of, cause of hemorrhage, i. 29 Blood vessels, influence of nervous system on, i. 232 innervation of, i. 175 pathological changes in, i. 44 shadow cast by in lung plate, i. 522 tuberculous lesions of, i. 241 Blood vessel walls, penetrated by ba- cilli, i. 124 Blotching of skin in anaphylaxis, ii. 160 Bodington, institutes open air cure for tuberculosis, ii. 228 Body, segmentation of, importance of understanding, i. 177 Body heat, eliminated largely through skin, ii. Ill Body temperature, normal regulation of, ii. 110 Bone and joint infection, percentage of bovine and human, i. 58 Bones, tuberculosis of, i. 106 Bonney, value of X-ray in diagnosis, i. 519 Bonniger, describes lymph stasis over pleurisy, ii. 60 Bouillon Filtrate (B. F.) Denys, ii. 354 Bovine and human infection, relative proportion of, i. 60 Bovine bacilli enter body same as hu- man, i. 62 Bovine infection, ii. 514 cannot be differentiated clinically, i. 61, 63 distribution of, i. 58 largely confined to childhood, i. 58, 59 prevalence of, i. 57 Bovine tuberculin, ii. 356 662 INDEX Bowditch, value of x-ray in diagnosis, i. 519 Brain, effect of bombardment of, with toxins, ii. 393 tuberculous ulceration of, ii. 189 Brain cells, degenerated in tubercu- losis, i. 160 Brannan establishes "Sea Breeze", ii. 268 Brauer and Spengler, artificial pneu- mothorax, ii. 429 Breathing, abdominal, makes auscul- tation difficult, i. 428 amphoric, over cavity, i. 492 deep, and prevention of tuberculo- sis, ii. 305 favors bronchogenic infection, i. 37, 452 ; ii. 306 hastens circulation, ii. 306 harsh, in advanced tuberculosis, i. 479 in early pulmonary tuberculosis, i. 433 impeded, in early pulmonary tuber- culosis, i. 431 method of, during auscultation, i. 428 rough, in advanced tuberculosis, i. 479 in early pulmonary tuberculosis, i. 430 muscle element in, i. 479 thoracic, due to assuming erect position, i. 128 weak, in early pulmonary tubercu- losis, i. 430 Brehmer, and curability of tuberculo- sis, ii. 190 establishes hygienic-dietetic treat- ment of tuberculosis, ii. 190 exercise in treatment of tuberculo- sis, ii. 282 Bromide in treatment, ii. 468 tuberculous meningitis, ii. 91 Bronchial secretion in anaphylaxis, ii. 159 Bronchial spasm in anaphylaxis, ii. 159 Bronchiectasis, bacilli rarely found in, ii. 588 differentiated from tuberculosis, i. 614 Bronchitis, an air-borne infection, differs from tuberculosis, i. 67 Bronchitis — Cont 'd and early clinical tuberculosis, i. 364, 390 as cause of asthma, ii. 164 as early symptom of tuberculosis, cases illustrating, ii. 537, 579, 582, 600, 603, 625, 632 chronic purulent, differentiated from tuberculosis, i. 614 differentiated from tuberculosis, i. 613 in advanced tuberculosis, i. 460 influence of fog on, ii. 267 Bronchitis, symptom of active tuber- culosis, case illustrating, ii. 563 tuberculous, ii. 527 Bronchogenous metastasis, i. 37 Brown, tuberculin book devised by, ii. 382 Browning, study of relationship of cli- mate and meteorological in- fluences on hemorrhage, ii. 170 Bruits, heart, i. 244 C Cajal, Eaymon Y., on similarity of action between sympathetic, spinal and cerebral nervous systems, i. 191 California, Southern, climate of foot hills of, ii. 255, 275 Calmette, artificial immunization, ii. 335 conjunctival tuberculin test, i. 502, 515 feeding experiments, i. 69 Cannon, emotions and peristalsis, i. 279 Capps, study of diaphragmatic pleu- risy, ii. 68 Carbon dioxide, deleterious influence of excess of, not proved, ii. 230 Carr, statistics of glandular tubercu- losis in childhood, i. 113 Case illustrating, acute caseous tuber- culosis, ii. 621 careful inspection in advanced tu- berculosis, i. 469, 470 chronic caseofibrous tuberculosis, ii. 553, 599, 609, 650, 659 INDEX 663 Case illustrating — Cont'd chronic fibrocaseous tuberculosis with marked contraction, ii. 590 chronic .fibroid tuberculosis with neurasthenia, ii. 524 chronic fibrosis, ii. 579, 631, 659 comparative results of examination by stereoscopic plate and physical examination, i. 526 extensive fibrocaseous tuberculosis, ii. 566 marked compensatory changes, i. 308 moderately advanced pulmonary tu- berculosis with slight casea- tion, ii. 534 rapidly forming fibrosis with lim- ited necrosis, ii. 542 recurrent pneumothorax, ii. 85 traumatic tuberculosis, i. 315, 316 tuberculous meningitis, ii. 94 value of spasm and degeneration in diagnosis, i. 400 Caseous tuberculosis, characteristics of, i. 41 Cathartics, evil effects of, i. 269 Cavity, amphoric breathing over, i. 492 blowing expiration over, i. 492 cracked pot sound over, i. 491 formation of, i. 28 healing of, shown at autopsy, ii. 597 Cavity, hemorrhage from tiny vessels in, ii. 173 in pulmonary tuberculosis, i. 489 pain when forming, i. 453 pitch of, expiratory low, i. 479 walls of, insensitive, i. 451 Cavity changes on, auscultation, i. 491 inspection, i. 489 palpation, i. 490 percussion, i. 490 Cell activity, all, under nerve control, ii. 390 Cell sensitization, degree of, shown by character of tuberculin reaction, i. 504 Cell sensitization prevents metastases, i. 34, 119 Cells, body, produce defensive fer- ments, ii. 197 difference in behavior, in primary and secondary infections, i. 82, 84 epithelial, in sputum, i. 536 Cells—Cont'd nerve, injured by toxins, ii. 392 of entire body, sensitized in tuber- culosis, ii. 337 protective properties of, vary at dif- ferent times, i. 108 sensitization of, effects implanta- tion, i. 34 changes character of metastases, i. 63, 82 shows in tuberculin reaction, i. 504 throughout body, ii. 342 wandering, carry infection, i. 36 Cellular activities, controlled by chemico-physical, sensorimo- tor, and psychical influences, i. 168 Centrifuge for determining sediment volume in sputum, i. 537 Chest, conditions within, which alter percussion note, i. 425 difference in, of child and adult, i. 126 important anatomical and physio- logical facts in examination of, i. 319 light percussion stroke felt through, i, 418 Chest wall, altered contour, in ad- vanced tuberculosis, i. 468 altered movement of, in advanced tuberculosis, i. 468 bulging of, in advanced tubercu- losis, i. 469 flattening of in advanced tubercu- losis, i. 469 movement of, lessened on affected side, i. 37 projection of lung on anterior sur- face of, i. 319 Chests, do not depart from normal in type, i. 471 Child, effect of infection upon, i. 108 gradually develops cellular defense, i. 34 greatest danger of infection during early years, i. 97; ii. 504 infection of, i. 95, 100; ii. 503 lacks cell sensitization, i. 34, 96 natural defense of, i. 93 protective role of lymphatics in, i. 93; ii. 505 specific defense increases with age of, i. 95; ii. 199 what predisposes, to infection, i. 99 664 INDEX Childhood, fate of infections in, i. 107 lymphatic disease of, and clinical tuberculosis in adult, i. 70 lymphatics peculiar in, i. 31 Children, country and infection, i. 79 frequency of infection in, i. 100 in tuberculous families have great- er immunity, i. 363 of tuberculous families, infection in, i. 362 seaside sanatoria for, ii. 267 time of primary infection, i. 95 yield readily to treatment, i. Ill Chilliness or rigor, part of syndrome of toxemia, ii. 110 Chilling, and ventilation of skin, ii. 251 Chloroform, dissolves interbacillary wax and distributes bacilli that are bunched, i. 549 Chromaffin system, part of sympa- thetic, i. 173 Chronic fibrosis, relationship to tuber- culosis, i. 615 Ciliary body, innervation of, i. 176 Ciliary muscle, innervation of, i. 176 Circulation, and nutrition, ii. 328 efficiency of, reduced by deficiency of inspiratory act, ii. 289 factors hindering in tuberculosis, i. 234 factors reducing efficiency of in tu- berculosis, ii. 289 hastened by deep breathing, ii. 306 influence of inspiratory act in, i. 301 pulmonary, i. 234 effects of obstructing, i. 235 Circulatory disturbances in advanced tuberculosis, i. 442 Circulatory stimulation in treatment of hemorrhage, ii. 179 Circulatorv system, and prognosis, i. 6*38 in tuberculosis, i. 230 physiological facts concerning, i. 234 City air, ii. 264 Classification, etiological, of early symptoms, i. 365 of physical changes in early tuber- culosis, i. 394 Cleaves, physical condition of sun, ii. 414 Climate, ii. 254 and prognosis, i. 647 bad, physiological influence of, ii. 261 cold, requires food, ii. 273 cold dry, effect of, ii. 268 cold moist, effect of, ii. 269 discussion of, partisan, ii. 261 dry, gives wide diurnal variation in temperature, ii. 269 dry low land, ii. 269 dry sunny, irritates nervous system, ii. 270 factors in, ii. 262 factors of, applied to different sec- tions of United States, ii. 269 factors which produce varied influ- ences of, ii. 268 hot, dry, effect of, ii. 268 hot, moist, effect of, ii. 268 important in all diseases, ii. 254 influence of wind in, ii. 268 inland, in therapeutics of tubercu- losis, ii. 268 man's power of physiological ad- justment to, ii. 257 moist low land, ii. 269 mountain, ii. 270 mountain, stimulating to metabol- ism, ii. 270 of Southern California, ii. 255 remnant of let alone policy, ii. 254 Clinical history, i. 363 importance of in diagnosis, i. 603 Clinical symptoms, meaning of, i. 86 Clinical tuberculosis, definition of, i. 358 relationship of, to primary metas- tases, i. 85 Clothing, effect on stagnation of body heat, ii. 246 for the tuberculous, ii. 250 Cloudy swelling, i. 44 Coccidiodal granuloma differentiated from tuberculosis, i. 621 Codein for relief of pain, ii. 457 in cough, ii. 447 Cod liver oil in treatment, ii. 467 Cohnheim, discussion on changes of blood at altitude, ii. 259 discussion on relationship of food intake to exercise, ii. 280 Coin sound in pneumothorax, ii. 81 Cold compress in cough, ii. 448 INDEX 665 "Colds," as early symptoms of tu- berculosis, cases illustrating, ii. 537, 542, 566, 570, 582, 600, 603, 621, 625, 650, 653 due to tuberculosis, ii. 527 frequent and protracted in ad- vanced, i. 460 in early tuberculosis, i. 390 tuberculous, accompanied by toxic symptoms, i. 607 when present, i. 607 Cole, Gregory, value of x-ray in diag- nosis, i. 518 Colitis, produced by raw eggs, ii. 326 Collapse in anaphylaxis, ii. 160 Colon, removal of, for tuberculous enteritis, case illustrating, ii. 654 , tuberculosis of, statistics of, ii. 36 Colonic injections in entercolitis, i. 265 Compensatory changes, between tho- racic and abdominal cavities, case illustrating, ii. 598 between thorax and abdomen, i. 295 case illustrating, marked, i. 308 in pulmonary tuberculosis, i. 281 within thorax, case illustrating, ii. 597 Compensatory disturbances, treat- ment of, i. 311 Compensatorv emphysema, caused by, i. 284 Congestion, venous, cause of, i. 44 Consciousness, loss of, in pneumotho- rax, ii. 79 Constipation, atonic, characteristics of, i. 271 treatment of, i. 271 , factors favoring, in tuberculosis, i. 269 spastic and atonic, i. 270 spastic, characteristics of, i. 275 treatment of, i. 275 Consumption, galloping, i. 41 Cook and Vander Veer, show inher- ited condition in hay fever, ii. 162 Coplin, pathology of changes in in- tercostal muscles in pleurisy, ii. 61 Cornet, experiments in inhalation tu- berculosis, i. 66 Cough, and posture, i. 451 as early symptom, i. 386 Cough — Cont 'd cause of, ii. 445 causes marked rise in temperature, case illustrating, ii. 616 Cough, depending on overflowing of cavities, i. 451 due to extreme traction on vagus, case illustrating, ii. 646 due to laryngeal irritation, ii. 448 effect of, deleterious, ii. 446 on temperature, case illustrating, ii. 645 rest upon, ii. 291 favors bronchogenic infection, i. 37, 452 in advanced tuberculosis, i. 45 , increases temperature, ii. 573 injury to the lung following, ii. 292 in tuberculous laryngitis, i. 26 much, can be avoided, ii. 446 treatment of, ii. 447 unnecessary, should be avoided, i. 452 wet jacket in treatment of, ii. 411 Country air, ii. 264 Covering, excessive, effect on temper- ature, ii. 155 Cracked pot sound over cavity, i. 491 Creosote in treatment, of cough, ii. 448 of tuberculosis, ii. 463 Crile, fever part of kinetic drive, ii. 117 kinetic system in defense, i. 219 on mechanism of fever production, i. 372 Croquet, a suitable game, ii. 299 Cytological examination of sputum, i. 536 i D Da Costa, D. C, Jr., dorsal percus- sion in mediastinal thicken- ing, i. 501 De la Camp, cause of trunk shadows in lung plate, i. 522 Defense, natural, of little child, i. 93 specific, broken down by, i. 107 cellular, and infection, i. 34, 64, 89, 112 commensurate with severity of in- fection, i. 600 determines nature of lesion, i. 63, 359 666 INDEX Defense, specific — Cont 'd developed after birth, i. 82; ii. 196 gradual development of in child, i. 34, 63; ii. 194 increases with age of child, ii. 199 prevents spread of disease, i. 120; ii. 198 Degeneration, amyloid, i. 43 cause of, i. 43 fatty, i. 44 general, of muscles, skin and sub- cutaneous tissue, i. 467, 474 pathological, of internal viscera, possibly due to reflex nerve stimulation, i. 606 regional, of muscles, skin and sub- cutaneous tissue, i. 179, 399, 405, 466 Deglutition, painful, in tuberculous laryngitis, ii. 26 Density of tissues determined by pal- "' pation, i. 476 Depressive emotions and fever, ii. 108 relieved by psychotherapy, ii. 389 D'Espine's sign, i. 115 Dettweiler and rest in treatment of tuberculosis, ii. 282 Diagnosis, and differential of tuber- culosis, i. 596, 612 cases illustrating comparative re- sults of x-ray and physical examination, i. 526 clinical, i. 360 relationship to infection, i. 359 clinical history in, i. 363, 603 condition of muscles and sub- cutaneous tissue in, i. 405, 410, 412, 466 deceptive not permissible, ii. 213 delayed, case illustrating, ii. 661 diaphragm and superficial muscle reflexes, value of in, i. 399, 468, 604 differential, between tuberculosis, cancer and syphilis of larynx, ii, 27 difficulties of, i. 597 difficulty of patient obtaining, case illustrating, ii. 557, 582, 583 dilatation of pupil in, i. 402 early, and prognosis, i. 642 depends on accurate conception of pathology, ii. 188 Diagnosis, early — Cont'd inspection in, i. 402 of tuberculosis, meaning of, i. 357 value of temperature in, i. 607 x-ray in, i. 611 examination of, blood in, i. 575 feces in, i. 578 sputum in, i. 534 urine in, i. 568 family history in, i. 361 hindered by long held pessimistic attitude, i. 597 importance of, altered contour of chest wall in, i. 468 altered movement of chest wall in, i. 468 careful, in advanced pulmonary tuberculosis, i. 435 in hidden tuberculosis, i. 596 muscles in, i. 399, 422, 428, 477, 535 cases illustrating, ii. 525, 535, 543, 554, 567, 580, 610, 622, 633 subcutaneous tissue in, i. 398, 410, 412, 422, 466, 498 cases illustrating, ii. 525, 535, 543, 554, 567, 580, 610, 622, 633 toxic group of symptoms in. i. 605 trophic changes in soft tissues over pleural adhesions in, ii. 60 tuberculin test in, i. 599 laboratory method in, i. 533 lagging in, i. 403, 468 made by correlation of data, i. 602 inspection and palpation, cases illustrating, ii. 526, 535, 543, 555, 567, 601, 611, 622, 633, 652 no stereotyped way of making, i. 361 not made when bacilli first enter tis- sue, i. 602 of active glandular tuberculosis, i. 114 of acute serofibrinous pleurisy, ii. 57 of pneumothorax, ii. 81 of tuberculosis of bladder, ii. 101 of tuberculous laryngitis, ii. 24 of tuberculous meningitis, ii. 91 past illness in, i. 364 patient should be told of, ii. 213 INDEX 667 Diagnosis — Cont 'd percussion in early, i. 417 pulmonary, method of using x-ray in, i. 524 relative importance of different groups of symptoms in, i. 603 should not depend on auscultation alone, i. 427 tuberculin test in, i. 502 conjunctival, i. 515 cutaneous, i. 512 intradermal, i. 515 percutaneous, i. 515 subcutaneous, i. 506 value of, changed contour in trape- zius muscle in, i. 407 lymphocytes in sputum, i, 582 palpation in, i. 409 physical examination in, i. 608 symptoms due to tuberculous processes per se in, ii. 537 x-ray in, i. 516 Diaphragm, altered position and func- tion of, i. 282, 305 changes in position of, in pneumo- thorax, ii. 79 factors in displacement of, i. 302 Diaphragm, importance to respiration, i. 296, 300, 325, 326 innervation of, i. 296, 325, 331 in diagnosis of pulmonary tuber- culosis, i. 401 in production of lagging, i. 403, 468 lessened motion of, i. 301 limited motion should be studied on easy respiration, i. 525 shown by x-ray, i. 525 marked displacement of, case illus- trating, ii. 595, 598 motor reflex in from lung, i. 403 position at different age periods, i. 321 reflex, diagnostic importance, i. 604 reflexly stimulated, causes lagging of chest wall, i. 403 Diaphragmatic pleurisy, ii. 67 Diarrhea, in anaphylaxis, ii. 159 not always accompanies ulceration of bowel, i. 52 often absent in tuberculous enteri- tis, case illustrating, ii. 644, 1 648, 658 tuberculous, diet in, ii. 46 hot applications in, ii. 47 opium in, ii. 47 Diarrhea, tuberculous — Cont 'd pharmacopeial remedies in, ii. 47 rest in, ii. 46 Diazo reaction and prognosis, i. 639 case illustrating, ii. 618 formula for making, i. 569 method of recording, i. 569 Diet, errors in, i. 280 in hemorrhage, ii. 181 rational, ii. 315 relation of, to nutrition, ii. 308 Digestion and harmone theory, i. 257 improved by psychotherapy, ii. 394 in stomach, disturbed by colloidal solution, i. 256 Digestive disturbances, in advanced tuberculosis, i. 439 part of syndrome of toxemia, ii. 110 Digestive system, and prognosis, i. 637 in tuberculosis, i. 251 reflex disturbances, in early tuber- culosis, i. 388 Dillingham, conservative treatment of genitourinary tuberculosis, ii. 100 Discontent, effect of, on temperature curve, ii. 146 Discouragement, effect of on tempera- ture curve, ii. 146 Disposition to tuberculosis, i. 117 Double personality in tuberculosis, i. 50 Dover's powder in treatment of pain, ii. 457 Droplet infection, i. 68; ii. 513 Dunham, normal trunk shadows in plate, i. 522, 523 Dupre, pathology of psychoses and psychoneuroses, i. 159 Dust as cause of, asthma, ii. 164 infection, ii. 512 Dyspnea, due to fat flabby condition, ii. 293 in advanced tuberculosis, i. 457 in pneumothorax, ii. 75 measures for relief of, i. 458 rest when present, ii. 292 Dyschezia, (Hertz), i. 273 E Ear, tuberculosis of, ii. 106 Eastwood shows percentage of bovine and human infections, i. 59 668 INDEX Eating, practical method for encour- agement of, ii. 314 Economic status in prognosis, i. 626 Effusion, pleural, shall it be removed, ii. 5 tuberculin aids in absorption of, ii. 59 Eggs, raw, limitation of, as food, ii. 324 produce colitis, ii. 326 Ellermann and Erlandsen, technic for examination of sputum, i. 551, 555 Elliot, internal secretions, i. 169 Embolism, gas, during artificial pneu- mothorax, ii. 441 Emotions, depressive, act centrally, i. 223 act on sympathetic, i. 189 cause loss of weight, i. 441 cause rise of temperature, ii. 146 effect of, i. 223, 224, 228, 279, 367; ii. 389 symptoms due to, i. 189 effect of, on gastrointestinal tract, i. 279 helpful and harmful act differently, ii. 394 Emphysema, compensatory, and arti- ficial pneumothorax, ii. 431 auscultation in, i. 495 changes in contour of chest in, i. 494 changes in motion of chest wall in, i. 494 how produced, i. 284 inspection in, i. 494 marked, cases illustrating, ii. 594, 597 palpation in, i. 495 percussion in, i. 495 respiratory note in, i. 478 roughened respiratory note in, i. 495 Emphysema of superficial structures in artificial pneumothorax, ii. 441 Endurance, lack of, part of syndrome of toxemia, ii. 110 loss of, in advanced tuberculosis, i. 438 Enema, in relief of loaded colon, i. 274 Enterocolitis in tuberculosis, i. 264 symptoms of, i. 264 treatment of, i. 264 Enteritis, tuberculous, ii. 33 a surface infection, i. 53, 90; ii. 33 bacilli in stool in, ii. 41 cathartics to be avoided in, ii. 45 change in motility in, i. 52 ; ii. 40 development of, cases illustrat- ing, ii. 618, 654 diet in, ii. 46 enemas in, ii. 47 factors predisposing to, i. 51, 90 ; ii. 35 found at operation, case illustrat- ing, ii. 643 frequency of, ii. 33 hemorrhage in, ii. 38 hot applications in, ii. 47 local irritations, predisposing factors in, ii. 36 lymph glands not common infec- tion in, i. 83 metastatic, ii. 34 muscle reflex in, ii. 43 nausea in, ii. 39 not recognizable by symptoms, cases illustrating, ii. 644, 657 nutritional changes in, ii. 39 operation for, case illustrating, ii. 593 operative measure in, ii. 44 pain in, ii. 40 pathology of, i. 51 ; ii. 37 perferation of intestine in, case illustrating, ii. 661 pulse in, ii. 42 reflex trophic changes as predis- posing factor in, ii. 37 rest in, ii. 46 retardation of intestinal contents favors, ii. 35 slow pulse in, case illustrating, ii. 658 stool in, ii. 41 stricture in, ii. 38 symptoms of, ii. 39 temperature in, ii. 42 treatment of, ii. 44 pain in, case illustrating, ii. 648 usually secondary, ii. 35 variable appetite in, ii. 39 Environment in prognosis, i. 626 Enzymes, cells stimulated, produce specific, i. 95 INDEX 669 Enzymes — Cont 'd specific proteolytic, split up tuber- culin, ii. 351 Esophagus reflex, ii. 647 Evans, graphic temperature chart used by, i. 381 Examination, advantages of method- ical, i. 395 of chest, fluoroscopic, importance of, i. 611 of sputum, cytological, i. 536 physical, altered by condition of muscles, i. 332, 398 subcutaneous tissue, i. 398 and tuberculin therapy, ii. 382 and x-ray, relative value of, i. 516 cases illustrating, ii. 525, 535, 543, 554, 567, 580, 591, 600, 610, 622, 632, 651 daylight preferable for i. 395 difficult, i. 608 etiological classification of changes in, i. 396 favorable conditions for, i. 394 in advanced tuberculosis, i. 464 value of, in diagnosis, i. 608 sitting posture best for, i. 395 Excavation, areas of, marked by per- sistent rales, i. 481 Excitement, effect of, on temperature curve, ii. 146 Exercise, and autoinoculation, ii. 203 calls for increased food intake, ii. 280 cause of more deaths than any other measure, ii. 298 caution in prescribing, ii. 297 effects of, ii. 295 on temperature curve, ii. 148 upon the heart, ii. 289 essential to highest state of health, ii. 283 for lung, ii. 204 graduated, in tuberculosis, ii. 301 in early afebrile tuberculosis, ii. 284 in treatment of, congestive hemor- rhage, ii. 180 tuberculosis, ii. 282 in tuberculosis, ii. 277 increases toxemia, ii. 284 indication for, ii. 295 individualization in use of, ii. 286 Exercise — Cont 'd method of instituting, case illus- trating, ii. 546, 548 not based on degrees of temper- ature, ii. 297 not taken before meals, ii. 296 physiology of, ii. 277 stimulates circulatory and respira- tory system, ii. 278 stimulates heat production, ii. 278 suitable for the tuberculous, ii. 298 technic of applying, ii. 295 walking best, for tuberculous, ii. 299 Exertion increases dyspnea, i. 457 Expiration prolonged by infiltration, i. 478 emphysema, i. 478 Exudate in tuberculous meningitis, ii. 88 Exudates, pleural, absorption of, i. 49 Eye, symptoms in tuberculous menin- gitis, ii. 90 F Face, flushing of, in early tubercu- losis, i. 389 Fallopian tubes, tuberculosis of, ii. 103 Family, instruction of, importance of, ii. 472 Family history, i. 361 meaning of open tuberculosis in, i. 262 Fanning, standard diet for tubercu- losis, ii. 316 Fat, to be avoided, ii. 312 Fat people, not necessarily healthy, ii. 312 Fatty degeneration, i. 44 Feces, bacilli in, i. 578 ; ii. 513 does not mean bowel infection, i. 579 when no sputum raised, i. 580 examination of for occult blood, i. 5.80 in tuberculosis, i. 578 frequency of bacilli in, i. 579 Feet, cold, cause of and relief for, ii. 251 Fenwick and Dodwell, statistics of colon infection, ii. 36 Fermentation, method of examining sputum, i. 553 670 INDEX Ferments, digestive protective action of, i. 251 Fever, absence of, does not mean ab- sence of clinical tuberculo- sis, i. 373, 378 a conservative process, ii. 121 an index of degree of toxemia, ii. 129 air baths in, ii. 455 and depressive emotions, ii. 108 and heat elimination, ii. 123 and heat formation, ii. 123 beneficial influences of, ii. 453 cannot be prevented when activity present, case illustrating, ii. 641 caused by bacilli gaining access to blood stream, ii. 156 caused by depressive emotions, ii. 146 cause of, ii. 108 in early tuberculosis, ii. 126 in tuberculosis, ii. 122, 286 central nerve stimulation in, ii. 109 charts of common type in advanced tuberculosis, i. 447 contributions to study of, ii. 113 diurnal variation in, ii. 109 effects of, confused with effects of toxemia, ii. 452 experimental, heat production and loss in, ii. 112 favors antibody formation, ii. 118 in advanced tuberculosis, i. 445 integral part of syndrome of tox- emia, ii. 116 interferes with growth of bacilli, ii. 118 in tuberculosis, meaning of, ii. 108 mixed infection not cause of, ii. 122 part of body defense, ii. 117 part of syndrome of toxemia, ii. 108, 110, 452 physiological, ii. 114 prevents multiplication of bacteria, i. 373 | produces cellular change, ii. 118 production of, ii. 285 protein as cause of, ii. 114, 116 discussion of, ii. 118 relation to nervous system, ii. 108 rest during, ii. 285 rest in bed in treatment of, ii. 454 result of deficient heat elimination, ii. 117 Fever — Cont 'd result of increased heat production, ii. 117 Fever, sympathetic stimulation in, ii. 110 treatment of, ii. 452 vasoconstriction of skin vessels in, ii. 108 Fibrocaseous tuberculosis, character- istics of, i. 41 Fibroid tuberculosis, characteristics of, i. 40 in prognosis, i. 629 Fibrosis, gradual formation of, cases illustrating, ii. 553, 594 in pulmonary tuberculosis, i. 489 may be extensive without bacilli being found, ii. 588 ultimately takes on necrosis, case illustrating, ii. 606 usually overlooked on examination, ii. 558 Fibro-ulceration tuberculosis, temper- ature curve in, ii. 129 Finsen, popularizes light therapy, ii. 422 Fischberg, beneficial effect of artifi- cial pneumothorax, ii. 433 statistics of infection in childhood, i. 102 in tuberculous and non-tubercul- ous families, i. 103 Fistula, in ano, relation of, to pulmo- nary tuberculosis, eases il- lustrating, ii. 653, 656 should not be operated during active pulmonary tuberculo- sis, cases illustrating, ii. 653, 656 Fliigge, droplet infection, i. 68 Fluoroscope, use of, to guide site of puncture in artificial pneu- mothorax, ii. 436 Fly as carrier of bacilli, i. 78 Foci, metastatic, small, produce no symptoms, ii. 192 of tuberculosis, stimulated by tu- berculin, ii. 332 pulmonary, distribution of, i. 125 Focus, hidden, dangerous, i. 599 primary, and primary metastatic, method of differentiating, i. 82 primary lung focus, i. 66, 82 tuberculous, activity in, case illus- trating, ii. 572 INDEX 671 Fog, and open air, ii. 252 increases bronchitis, ii. 267 produces chill, ii. 267 Food, ii. 308 amounts of, on rest and exercise, ii. 318 required, vary according to condi- tion, ii. 321 and prognosis, i. 649 j increased amounts required for ex- ercise, ii. 280 open air causes greater demand for, ii. 248 suited to digestive powers of pa- tient, ii. 327 type of, in atonic constipation, i. 271 value of, cereals, ii. 320 fats, ii. 320 fruits, ii. 319 household measures of, ii. 322 meat and milk products, ii. 319 raw eggs, ii. 324 Foods, allowed in entercolitis, i. 266 caloric value of, ii. 316 easily digested, ii. 308 forbidden in entercolitis, i. 266 Foot bath, importance of, ii. 412 Forest, psychological effect of, ii. 263 Forlanini, artificial pneumothorax, ii. 429 Freund's theory critically examined, i. 135 Freund's theory of shortening of first rib and ossification of first costal cartilages, i. 133 Friedberger and Mita, studies in ana- phylaxis, ii. 344 and tuberculin reaction, ii. 336 Functional activity, normal variation in, i. 334 Furniture should be simple, ii. 511 G Games in tuberculosis, ii. 298, 301 Ganglia, of sympathetic system, i. 172 sympathetic, can reflexes take place in, i. 191 sympathetic, question whether im- pulse interrupted in, i. 190 Gas, amount injected in artificial pneumothorax, ii. 436 Gaskell, involuntary nervous system, i. 169 Gastrointestinal, symptoms during toxemia, i. 270 Gastrointestinal tract, effect of emo- tions on, i. 279 in tuberculous meningitis, ii. 90 nervous influences in, i. 278 reflex disturbances of, from lung, i. 253 Generative organs, muscles of, sup- plied by sympathetics, i. 176 Genitourinary infection, percentage of, human and bovine, i. 59 Genitourinary system, tuberculosis of, ii.,96 Ghon, primary lung foci of, may be intestinal infections, ii. 34 focus, i. 66 pulmonary foci and regional lymphatic glands, i. 30, 83 statistics showing distribution of pulmonary foci, i. 125 Glands, bronchial, diagnosis of tuber- culosis in, i. 114 increased activity of, during infec- tion, i. 107 infection of peritracheal and peri- bronchial, i. 32 lymphatic, bacilli pass through in childhood, i. 31 protect child against infection, ii. 196 mediastinal, infected by bacilli in- jected into rectum, i. 30 mesenteric, infection of, case illus- trating, ii. 658 peribronchial, projection on sur- face, i. 323 regional, markedly involved in pri- mary infections, i. 83 not markedly involved in second- ary infection of lung, larynx and intestine, i. 83 tuberculosis of, i. 54, 112 by age periods, i. 113 Glandular infection, relationship to clinical tuberculosis, i. 87 tuberculosis, diagnosis of, i. 114 Gley, E., internal secretions, i. 159 Goodbody, Bardswell and Chapman, diets for tuberculous pa- tients, ii. 315 Graduated exercise in tuberculosis, ii. 301 Griffith shows percentage of bovine and human infections, i. 58 Gram-positive but non-acid-fast ba- cilli, i. 559 Graves, scaphoid scapula, i. 471 672 INDEX H Habitus phthisicus, i. 147 Hamburger, primary lung focus, i. 66 statistics of, fatal and chronic tu- berculosis by age periods, i. 97 healing by age periods, i. 97 infection in childhood, i. 101 mortality by age periods, i. 97 Harbitz, statistics of postmortem tu- berculosis among children, i. 101 Hart's statement of Freund's theory, i. 135 Hart's statistics of healing of apical infections, i. Ill, 406; ii. 191 Hay fever, due to anaphylaxis, ii. 157, 161 inherited vagotonia in, ii. 162 Head, emphasizes sensory disturbance of skin, i. 454 Head's zones, i. 181 Headache, in tuberculous meningitis, ii. 89 part of syndrome of toxemia, ii. 110 Healing, clinical and pathological, not identical, case illustration, ii. 607 depends on tuberculin, ii. 333 determined by disappearance of muscle spasm, i. 411 evidences of, in clinical tuberculo- sis, ii. 193 important principles of, ii. 192 in advanced tuberculosis, difficult, ii. 201 in tuberculosis, why aided by tu- berculin, ii. 348 not synonymous with cessation of symptoms, ii. 194 occurs in extensive active lesions, case illustrating, ii. 575 of more recent tubercles stimulated by tuberculin, ii. 349 readily produced in early tuberculo- sis, ii. 200 requires long time, ii. 383, 564 shown at autopsy, ii. 594 slowness .of, case illustrating, ii 540, 563, 588 spontaneous, in tuberculosis, statis- tics of, ii. 191, 193 statistics of, by age periods, i. 97 Heart, action of, improved by open air, ii. 248 clinical evidence of failing, i. 248 condition of, calling for rest, ii. 291 death from dilatation of, ii. 574 difficulty in examining, in tubercu- losis, i. 242 dilated, treatment of, case illustrat- ing, ii. 605 displacement of, i. 242, 282, 286, 292 cases illustrating, ii. 598, 613 depends on size of pericardium, i. 286; ii. 598 effects of, i. 292 in pneumothorax, ii. 80 in tuberculosis, i. 283, 286, 288, 291 effect of, rest and exercise upon, ii. 289 tuberculosis upon, i. 236 explanation of variability in action, i. 387 failing, treatment of, i. 249 hypertrophy of right ventricle of, i. 240, 444 importance of good, i. 230 in advanced tuberculosis, i. 442 in pneumothorax, ii. 78 in prognosis, i. 443 marked displacement of, to right, ii. 595, 597 must be carefully guarded in pul- monary tuberculosis, ii. 289 nervous influence upon, i. 230 organic lesions of, and tuberculosis, i. 243 rapid, part of syndrome of tox- emia, ii. 110 reflex disturbance of, in early tu- berculosis, i. 387 reflexly slowed by pulmonary in- flammation, i. 231; ii. 551 reserve power of, i. 307 slowing of, showing vagus stimula- tion, case illustrating, ii. 618, 629 small, cause of, i. 148, 149, 239, 303, 444 sudden acceleration of, in pneumo- thorax, ii. 82 sympathetic and greater vagus ac- tion on, i. 199; ii. 110, 551 sympathetic stimulation, case illus- trating, ii. 618 INDEX 673 Heart — Cont 'd terminal dilatation of, case illus- trating, ii. 629 Heart block, partial, case illustrat- ing, ii. 572 Heart bruits, i. 244 Heart displacement, symptoms of, i. 1 13, 292 to left, i. 288 to right, i. 291; ii. 595 Heart murmur, musical, ease illus- trating, ii. 602 j Heart muscle, degeneration of, i. 244 Heart strain, case illustrating, ii. 594 in tuberculosis, symptoms of, ii. 290 Heat, comparative amounts for rest and work, ii. 279 in treatment of pain, ii. 457 reduced, elimination of, largest fac- tor in fever production, ii. 122 skin, most important factor in regu- lating, ii. 403 Heat loss, controlled by central nerv- ous system, ii. 115 Heat production in fever, cause of, , ii. 113 Heat stagnation, effects of, ii. 235 Hectic flush, in advanced tuberculo- sis, i. 458 sympathetic and greater vagus in production of, i. 199 Heise and Sampson, value of x-ray in diagnosis, i. 519 Heliotherapy, ii. 414 and prognosis, i. 648 case illustrating use of, ii. 548 technic of applying, ii. 424 Hematogenous infection, i. 38 accounts for metastases in distant organs, i. 38 Hematogenous metastases, mild be- cause of antibacillary ele- ments in blood, i. 38, 64 Hemorrhage, a sign of early tubercu- losis, ii. 169, 542, 579, 609, 622, 632 a symptom due to tuberculous proc- ess per se, ii. 164 accompanies necrosis and caseation, case illustrating, ii. 614 aconite, veratrum viride, pituitrin and nitrites, in treatment of, ii. 178 amount of, ii. 168 Hemorrhage — Cont 'd and advanced tuberculosis, i. 461 artificial pneumothorax, in treat- ment of, ii. 180 attention to bowels in, ii. 182 baths during, ii. 183 cause of, ii. 168 character of, in infarct, i. 616 climatic and meteorological influ- ence in production of, ii. 170 caused by arteries resisting obliterating effect of tuber- culosis, ii. 171 coagulability of blood in, ii. 178 complications following, ii. 183 congestive or toxic type, ii. 174 diet in, ii. 181 does not indicate patient not doing well, ii. 577 due to expulsion of necrotic mass, ii. 172 dry weather and, ii. 170 exercise in treatment of congestive, ii. 180 foggy weather and, ii. 170 followed by, extension of disease, ii. 184 miliary tuberculosis, ii. 184 pneumonia, ii. 177, 183 severe anemia, ii. 172 shock, ii. 184 follows rapid caseation, case illus- trating, ii. 626 follows swimming, ii. 300 frequency varies with material, ii. 168 from cavity, i. 28; ii. 173 importance of preserving clot in rupture after, ii. 175 in pulmonary tuberculosis, ii. 168 in tuberculous enteritis, ii. 38 makes diagnosis of tuberculosis al- most certain, i. 607 may come any time prior to heal- ing, ii. 564 mental rest in, ii. 176 morphine in treatment of, ii. 176 not beneficial per se, ii. 184 overexertion as cause of, ii. 168 pharmacological remedies in, ii. 177 physical rest in, ii. 177, 288 pneumococcus as cause of, ii. 177 prevention of, ii. 168 rainy weather and, ii. 170 rarely fatal, ii. 181 result of, ii. 184 674 INDEX Hemorrhage — Cont 'd severe, due to aneurism or erosion of vessel, ii. 171 treatment of, ii. 174 by concentrated salt solution, ii. 179 case illustrating, ii. 617 tuberculin stopped during, ii. 182 type of, treated by circulatory stim- ulation, ii. 179 Hemorrhages, appear in groups, ii. 170 differentiation of types, difficult, ii. 174 different types of, explained, case illustrating, ii. 617 types of, ii. 171 Heroin in cough, ii. 447 Hertz, cause of atonic constipation, i. 272 esophagus reflex, ii. 647 Higier, vegetative and visceral neu- rology, i. 169 Hill, studies on open air, ii. 230 Hilus, infection, i. 54, 110, 112 diagnosis of, i. 114 importance of, i. 596 involved, no matter how bacilli en- ter body, i. 31 Hilus, normal shadow in x-ray plate, i. 521 Hilus, palpation in examination of, i. 115 Hinsdale, discussion of climate, ii. 255 variability of oxygen and carbon dioxide in air, ii. 263, 265 History, clinical, eases illustrating, ii. 534, 542, 553, 566, 579, 590, 599, 609, 621, 631, 650, 659 of tuberculosis, ii. 524 Hoarseness, due to tuberculosis, usu- ally accompanied by other symptoms, i. 603 in advanced tuberculosis, i. 447 in early active tuberculosis, cases illustrating, ii. 527, 554, 566, 591, 600, 622, 625, 650 in tuberculous laryngitis, ii. 24 method of its production, i. 385 Holmes, changes in neutrophile, i. 577 Holzknecht, cause of trunk shadows in lung plate, i. 522 Home treatment, ii. 470 care of sputum in, ii. 478 diet must be prescribed carefully in, ii. 474 how arrange home for, ii. 471 how often see patient in, ii. 480 over anxiety of friends must be avoided in, ii. 473 problems of, ii. 470 prognosis in, i. 645 program for, ii. 476 training family for, ii. 472 training patient for, ii. 475 Homogenization of sputum, advan- tage of, i. 552, 554 Hope, effect of, on patient, ii. 391 essential to cooperation, ii. 395 Hopefulness of patient, i. 155 Hormone, theory and digestion, i. 257 Horseback riding, not suitable, ii. 299 Hospital, general, is tuberculosis a danger in, ii. 518 Hot water bottles, use of, to be dis- couraged, ii. 250 Huggard, discussion of climate, ii. 254 Humidity of atmosphere, effect on body, ii. 243, 258 Huntington, discussion of climate, ii. 255 Hydrotherapy, ii. 401 and prognosis, i. 649 Hygiene, personal, of patient, ii. 512 Hyperchlorhydria, during toxemia caused by reflex stimulation of vagus, i. 260 in tuberculosis, i. 260 treatment of, i. 261 Hyperesthesia and hyperalgesia, of skin in tuberculosis, i. 453 Hypersensitiveness, precipitated by rapid cleavage of protein, ii. 347 to tuberculin, ii, 347 Hypersthenic type of individual, char- acteristics of, i. 339 Hypochlorhydria, in tuberculosis, i. 259 treatment of, i. 259 Hypophosphates in treatment, ii. 467 Hyposthenie type of individual, char- acteristics of, i. 348, 355 Hypotension, effects of, i. 306 INDEX 675 Immunity, and infection, i. 95 child gradually develops, i. 96 greatest in children of tuberculous families, i. 362 high degree of, in tuberculosis, i. 96, ii. 330 in tuberculosis, relative, i. 96; ii. 195 produced by tuberculin, ii. 330 Immunization, active, experiments on, i. 96 artificial attempts at, ii. 335 Imperial German Board of Health's statistics of bovine and hu- man infection, i. 58 Improvement may occur in spite of serious symptoms, ii. 619 Impulse, afferent third and fourth cervical segments of cord center of, from lug, i. 181 "Incipient tuberculosis, ' ' i. 357 a misnomer, ii. 283 Incubation period in tuberculosis, i. 65 Indican and overfeeding, i. 587 method of determining, i. 572 weather, i. 587 Infarct, pulmonary, differentiated from tuberculosis, i. 616 Infection, aerogenous, i. 29, 6Q difficulties of, i. 67 alimentary, i. 69 and immunity, i. 95 avenues of, i. 29 bovine, ii. 514 bronchial, favored by cough and deep breathing, i. 37, 452; ii. 306 danger of, lessened by artificial pneumothorax, ii. 433 dangerous until healed, ii. 195 droplet, i. 68; ii. 513 dust, ii. 512 early, semiquiescent, effect on growth, case illustrating, ii. 603 symptoms not recognized, case il- lustrating, ii. 570 effect of, upon child, i. 108 fate of early, i. 107 finger nails, source of, i. 73 follows course of soot, i. 134 frequency of in adult lung, i. 406 from without in adult life, i. 89 Infection — Cont 'd in children of tuberculous families, i. 362 in pneumothorax, ii. 79 intestinal and mesenteric glands, i. 71 in tuberculous families, i. 103 lessened danger of, to adults, i. 92 localization of, i. 31 differs in child and adult, i. 124 differs with changes in bony thorax, i. 130 lymphatic structures protect child against, ii. 196 metastatic, early clinical tubercu- losis, ii. 189 method of, ii. 21 mixed, not common in tuberculosis, ii. 122 not spread in sanatoria, ii. 519 of child, ii. 503 of larynx, cause of, ii. 20 primary and metastatic contrasted, i. 82 primary intestinal, ii. 33 pulmonary localization of, depends on anatomical and develop- mental factors, i. 123 reflex changes in superficial soft tissues, as result of, i. 397 relationship to clinical diagnosis, i. 359 relative difficulties of infection from without and within, i. 89 size of, important, i. 92 source of, i. 57 difficulty of determining, i. 78 through skin, i. 80 through skin, i. 80 uninjured mucous membrane, i. 30 what predisposes child to, i. 99 without cellular defense, i. 34 Infiltration, pulmonary, changes on auscultation in, i. 488 inspection in, i. 482 palpation in, i. 484 percussion in, i. 485 diagnosis of, i. 482 Infiltrations, determined by palpa- tion, i. 413 Inflammation, collateral, cause of, i. 26 exudative, ii. 349 676 INDEX Inflammation, collateral — Cont 'd injures tissues, i. 86 nature of, i. 26 undergoes same change as tuber- cle, i. 26 tuberculosis, characteristic of, i. 27 Influenza, active tuberculosis often diagnosed as, ii. 659 and tuberculosis, differentiation of, i. 614 Ingestion, of bacilli, historical sketch, i. 75 of inhaled bacillli, i. 72 Inhibition in visceral nerves, i. 174 Inland climates, ii. 268 Innervation of muscles of forced res- piration, i. 327 Insanity and tuberculosis, i. 150 Insomnia, cause of, ii. 458 treatment of, ii. 459 Inspection, a most important but neg- lected method of diagnosis, i. 402 cases illustrating careful, in ad- vanced tuberculosis, i. 469 condition of subcutaneous tissue de- termined by, i. 405, 466 in advanced tuberculosis, i. 464 in compensatory emphysema, i. 494 in diagnosis, i. 402, 464 cases illustrating, ii. 526, 535, 543, 555, 567, 601, 611, 622, 633, 652 in dry pleurisy, i. 496 in mediastinal tumors, i. 500 in pleural effusion, i. 496 in pulmonary cavity, i. 490 infiltration, i. 482 in thickened pleura, i. 497 lagging detected by, i. 404, 468 may show evidence of active pulmo- nary lesion, i. 402, 468 muscle spasm and degeneration de- termined by, i. 405, 466 of great value in diagnosis, i. 397, 402, 464 probable diagnosis made by, i. 464 rules for, i. 464 Inspiratory act, i. 295 increases circulatory efficiency, i. 301; ii. 289 results of lessening, i. 303 symptoms of deficiency in, i. 303 Intercostal muscles, changes in, in pleural adhesions, ii. 59 pathological changes in, in pleuri- sy, ii. 61 Intercostal neuralgia, and early clin- ical tuberculosis, i. 364 and tuberculosis, differentiation of, i. 613 Intercostal spaces, bulging of, in pneumothorax, ii. 80 Intercostals, innervation of, i. 325 Internal secretion of ovary, i. 195 suprarenal gland, i. 173, 219, 605 Internal secretions, influence symp- toms, i. 194, 228 relation to toxic state, i. 366 Internal viscera, degenerative changes in, possibly due to reflex irri- tation, i. 606 Intertransmissibility of bovine and human bacilli, i. 57 Intestinal canal, innervation of, i. 176 mucous membrane of child, easily penetrated, i. 71, 100 route of infection, i. 53 stasis in tuberculosis, i. 266 tract, motility of, in anaphylaxis, ii. 160 Intestine, disturbance of, in tubercu- losis, i. 215, 264 lungs embryologically formed from, i. 181; ii. 165 performation of, in tuberculous en- teritis, case illustrating, ii. 661 primary infection of, i. 52 sympathetic and greater vagus ac- tion on, i. 211, 215 thickening of wall of, in tuber- culous infection, case illus- trating, ii. 656 tuberculosis of, {see Enteritis, tu- berculous) tuberculosis of, in prognosis, i. 632 Intrathoracic pressure negative, i. 302 Iodine in treatment, ii. 465 Iron in treatment of tuberculosis, ii. 468 Itching of skin in anaphylaxis, ii. 160 Jacob, study of infection of country children, i. 79 INDEX 677 Jobling and Peterson, action of io- dine, ii. 465 Joint and bone infection, percentage of, bovine and human, i. 58 Joints, tuberculosis of, ii. 106 Jona, heat production and loss during experimental fever, ii. 112 Joseph, incubation period in tubercu- losis, i. 65 K Katathermometer, description and in- struction for use of, ii. 238 Keith, believes lessened expansion fa- vors implantation, i. 147 human embryology and morphology, i. 169 Kellogg discusses variety of nerves supplying skin, ii. 401 Kernig's sign in tuberculous menin- gitis, ii. 90 Kidd, statistics of aneurism and fatal hemorrhage, ii. 172 Kidney, tuberculosis of, ii. 96 tuberculous, catheterization may give no evidence in, ii. 98 clinical healing of, ii. 100 healing of, ii. 97 operation for, ii. 97 pain in, ii. 98 routes of infection in, ii. 96 spasm of lumbar muscles in, ii. 98 symptoms of, ii. 97 treatment of, ii. 100 tuberculin treatment of, ii. 100 urine in, ii. 98 Kidneys, both may be infected, yet not show in urine, ii. 97 Kime, reflector for sun treatment, ii. 427 Kinetic system (Crile), i. 219 Kinyoun's method of using mechan- ical shaker, i. 555 Klebs, what sanatorium stands for, ii. 484 Knopf, advantages of sanatorium treatment, ii. 482 Koch, and intertransmissibility of bo- vine and human bacilli, i. 57 and tuberculin reaction, ii. 336 artificial immunization, ii. 335 Koch's, experiment showing cell sen- sitization, i. 82 idea of primary intestinal infection, i. 52; ii. 33 Konig, favors operation for tubercu- lous peritonitis, i. 50 Krause, and tuberculin reaction, ii. 336 tuberculin hypersensitiveness and character of lesion, i. 505 Krumwiede, shows relative percentage of bovine and human infec- tion, i. 58 Laboratory, findings, aid in diagno- sis and in understanding of complications, i. 481 correlation of, i. 589 case illustrating, i. 593 interpretation of, i. 581 of limited prognostic value, i. 501 methods, i. 533 Lagging, cause of, i. 403 decreased elasticity of pulmonary tissue, as cause of, i. 403 detected by inspection, i. 403 palpation, i. 416 due to diaphragm reflex through phrenics, i. 403, 468 of both sides difficult to detect, i. 404, 416 overcome by deep breathing, i. 404 regional and general, how detected, i. 403 value of, as diagnostic sign, i. 403 La grippe and early clinical tuber- culosis, i. 364 Lampson, statistics of infections in tuberculous families, i. 103 Landis, pulmonary syphilis, i. 619 Laryngitis, tuberculous, ii. 17 case of, ii. 20 cough in, ii. 26 diagnosis of, ii. 24 differentiated from syphilis and cancer, ii. 27 frequency of, ii. 18 hoarseness in, ii. 24 laryngologist 's and chest special- ist's opinions of, differ, ii. 31 lymph glands not commonly in- volved in, i. 83 obstructed respiration in, ii. 26 pain in, ii. 25 painful deglutition in, ii. 26 pale mucous membrane in, ii. 28 pathology of, i. 47 678 INDEX Laryngitis, tuberculous — Cont'd percentage in male and female, ii. 19 prognosis in, ii. 23 secretion in, ii. 26 treatment of, ii. 28 tuberculin in diagnosis of, ii. 28 Larynx, and bifurcation of trachea, points of increased sensibil- ity, i. 451 incidence of infection of, depends on pulmonary condition, ii. 19 irritation in, as early symptom, i. 386 directs attention away from lungs, i. 387 location of infection in, i. 47 method of infection of, i. 90; ii. 21 neuritis of, i. 450 percentage of infection in, i. 48 should be routinely examined, ii. 18, 26 surface infection of, i. 47 throat compress in treatment of, ii. 411 tuberculin reaction in, ii. 18 tuberculosis of, case illustrating, ii. 592, 626, 630 in prognosis, i. 631 secondary, i. 47 treated by tuberculin, ii. 384 tuberculous process in, easily stud- ied, ii. 17 Latent tuberculosis, dangerous to pa- tient, i. 110 importance of recognizing in early life, i. 110 Latham, advantages of sanatorium treatment, ii. 482 Lee, studies on open air, ii. 230 Lesions, apical, activity in, determined by inspection and palpation, i. 407 Leucopenia and miliary tuberculosis, i. 591 Levastine, degeneration of brain cells, i. 160 Levator anguli scapulae, innervation of, i. 331 spasm and degeneration of, in diag- nosis, i. 401 Lewandowsky, function of central nervous system, i. 169 Light, application of, in treatment, ii. 421 augments oxidation, ii. 420 blondes versus brunettes, as af- fected by, ii. 426 dosage important, ii. 427 effect of, on bacteria, ii. 418 on blood, ii. 420 on human being, ii. 420 on skin, ii. 418 energy of, consists of vibrations, ii. 215 fundamental principles of, ii. 414 penetration of tissues by, ii. 419 physiological effects of, ii. 418 sun, concentrated as a bath, ii. 427 ultraviolet, percentage reaching earth, ii. 417 suffers loss in atmosphere, ii. 417 vibration rate of various colors of, ii. 415 Ligroin in examination of sputum, i. 555 Liver, tuberculosis of, i. 53 Lobes, position of divisions between, i. 321 Lord, on cause of pleural effusion, ii. 84 Lung, antagonistic action of sympa- thetic and greater vagus in the production of symptoms when inflamed, i. 198 early metastases in, fibroid in char- acter, i. 36; ii. 189 effect of compression of, ii. 430 embryologically formed from intes- tine, i. 181; ii. 165 exercise for, ii. 204 growth of, at different age periods, i. 127 infected by bacilli injected into rec- tum, i. 30, 71 infection of, from within and with- out, difference in, i. 89 through intestine, i. 72 inflammation of, causes reflex changes in chest muscles and subcutaneous tissues over them, i. 408 injury during artificial pneumotho- rax, ii. 441 malignant tumors of, i. 621 marked compensatory changes in, shown at autopsy, ii. 594 motor reflex from, i. 454 INDEX 679 Lung— Cont 'd necrosis and caseation of, case illus- trating, ii. 613 nerve supply of, i. 179 primary foci in, may result from intestinal infection, ii. 34 projection of, on anterior surface of chest wall, i. 319 receives innervation from sympa- thetic and vagus, i. 180, 192, 198 reserve area of, i. 285 rest for, ii. 304 sensory area of skin from, i. 454 sympathetic nerve supply of, i. 180 why so often infected, i. 32 Lung focus, relationship to glands, i. 30, 83, 89 Lungs, motor segmental relationship to body surface, i. 179 normal borders of, i. 320 segmental relationship of, i. 179 sensory segmental relationship of, to body surface, i. 179 Lymph, and blood flow influenced by stimulation of skin, ii. 402 Lymph flow, favored by respiration, i. 37 Lymph spaces, widened by inspiration, favor infection, i. 36 Lymph stream, bacilli may be carried against, i. 37, 62 Lymphatic infection, favored by, i. 37 in child and clinical tubercuolsis in adult, i. 70, 110 Lymphatic system, tuberculosis pri- marily a disease of, i. 32, 48, 55 Lymphatic tissue, importance of in childhood, i. 93 Lymphatic tuberculosis, in early life, importance of, i. 110, 112 Lymphatics, part in disseminating in- fection, i. 55 role of, in protection of child, ii. 505 subpleural, absorptive power of, i. 49 Lymphocyte count, high, questionable diagnostic value of, i. 585 Lymphocytes in sputum, i. 536 diagnostic value of, i. 582 M Mackenzie emphasizes sensory disturb- ance of skin, i. 454 Malaise, in tuberculosis, i. 369, 438 part of syndrome of toxemia, i. 223, 226; ii. 110 Malaria and early clinical tuberculo- sis, i. 364, 612 Malignant tumors of lung, i. 621 Mammary gland, degeneration of, sign of reflex trophic change from inflammation in lung, i. 409 Manteaux, intradermal tuberculin test, i. 502, 515 Maragliano and artificial immuniza- tion, ii. 335 Marriage and tuberculosis, ii. 516 Mattison, resection of cecum and as- cending colon, case illustrat- ing, ii. 654 Maxwell shows colloidal solution re- tards gastric digestion, i. 256 McCarthy and Carncross, statistics of mental attitude of the tuber- culous, i. 153 McCarthy, describes tuberculous ul- ceration of brain substance, ii. 89 McGowan, on conservative treatment of genitourinary tuberculo- sis, ii. 100 Mechanical shaker, in examination of sputum, i. 554 Mediastinal thickening, in advanced tuberculosis, i. 499 Mediastinum, displacement of, in pneumothorax, ii. 79 part in compensatory changes, i. . 282 shifting of, i. 285, 293 Medical guidance, tuberculous patient requires close, ii. 223 Medical profession, ability of, to cope with tuberculosis, im- proving, ii. 209 prevailing attitude of, toward tu- berculosis, ii. 208, 210 Mehnert, shows inclination of ribs at different age periods, i. 128 Meningitis, tuberculous, ii. 88 cause of, ii. 88 diagnosis of, ii. 90 exudate in, ii. 88 eye symptoms in, ii. 90 680 INDEX Meningitis, tuberculous — Cont 'd fever in, ii. 89 gastrointestinal tract in, ii. 90 headache in, ii. 89 healing may follow, ii. 88, 91 in prognosis, i. 633 Kernig 's sign in, ii. 90 muscle rigidity in, ii. 90 nervous system in, ii. 89 pulse in, ii. 89 symptomatology, ii. 89 treatment of, ii. 90 Menopause, and ovarian secretion, i. 195 premature in advanced tuberculosis, i. 462 Menstrual period, less resistance dur- ing, i. 462 nervous symptoms during, i. 462 Menstrual rise, in temperature, i. 380 ; ii. 149 Menstrual wave, cause of, i. 195 Menstruation, and ovarian secretion, i. 195 in advance tuberculosis, i. 461 vicarious, i. 391 Mental attitude, in tuberculosis, i. 153, 156 Mental processes, disturbed in tuber- culosis, ii. 393 Mental state, in prognosis, i. 628 Menthol, in treatment of tuberculous enteritis, case illustrating, ii. 648 Metabolism, changes with weather in- fluences, ii. 275 improved by open air, ii. 244, 248 increased by exercise, ii. 277 stimulated by, cold, ii. 272 sunlight and air currents, ii. 270 Metallic tinkling, in pneumothorax, ii. 81 Metastases, follow activity in existing focus, case illustrating, ii. 626 hematogenous, i. 31, 38 in lung, early, fibroid in character, i. 35, 85; ii. 189 lymphatic, i. 36 primary, and primary focus, i. 82 relation to clinical tuberculosis, i. 85 production of, hindered by cellular defense, i. 35; ii. 198 pulmonary, factors favoring, i. 120 secondary, i. 35 Metastatic tuberculosis, i. 118, 359 Miliary tuberculosis, acute, tempera- ture curve of, ii. 128 and leucopenia, i. 591 cause of, i. 40, 241 in prognosis, i. 628 Miller, establishes open air school for tuberculous children, ii. 268 Mills, the relation of visceral form, topography and function to the general physique, with classification of types, i. 335 Minor, value of x-ray in diagnosis, i. 518 Mixed infection, argument against, from pneumothorax, ii. 83 not common in tuberculosis, ii. 122 Moro, percutaneous tuberculin test, i. 502, 515 Morphine, in treatment of hemor- rhage, ii. 176 Mortality by age periods, i. 97 Motility, changes in, in tuberculous enteritis, ii. 40 Motor reflex, from diaphragm, i. 403 from intestines, ii. 43 from kidney, ii. 98 from lungs, paths of, i. 179 Much, and artificial immunization, ii. 335 Much's granules, stain for, i. 559 Mucous membranes, adaptation of to climatic change, ii. 258 Municipality, duty of, in preventing tuberculosis, ii. 514 Murphy, artificial pneumothorax, ii. 429 Muscle, normal, description of, i. 406, 411 Muscle changes, interpretation of, i. 405, 407 Muscle degeneration, cause of, i. 399 condition described, i. 412, 474 description of, as sign of chronic pulmonary inflammation, i. 412 in advanced tuberculosis, i. 466 regional, denotes chronicity, i. 412, 466, 473 Muscle reflex, disappears when inflam- mation heals, i. 411 importance of, in diagnosis, i. 610 in tuberculous enteritis, ii. 43 method of determining, i. 411 INDEX 681 Muscle rigidity, symptom of tubercu- losis enteritis, case illustrat- ing, ii. 660 Muscle spasm, cause of, i. 399 description of, i. 406, 411 in advanced tuberculosis, i. 466 regional, denotes activity, i. 399, 412, 466, 473 Muscles, and other soft tissues, effect of on palpation, percussion, and auscultation shown by thickness of, i. 332 and subcutaneous tissue, influence on percussion, i. 422 over thickened pleura, i. 498 condition of, alters, auscultation, i. 398 palpation, i. 398 percussion, i. 398 in active tuberculosis, i. 399; ii. 525 in moderately advanced tubercu- losis, ii. 535 degeneration of, from use, i. 475 lowers percussion note and de- creases resistance, i. 477 effect of, occupation upon, i. 333, 405, 413 on respiratory note, i. 428, 479 increased tone in, raises percussion note and increases resistance, i. 477 in diagnosis, cases illustrating, li. 525, 535, 543, 554, 567, 580, 610, 622, 633 influence of, on physical findings, i. 332 involved in reflex from lung, i. 179, 408 respiration, i. 296, 326 lumbar, spasm of, in tuberculosis of kidney, ii. 98 part of, in deformity of bony tho- rax, i. 294 pathological changes in, i. 44, 399, 405 vs. occupational changes in, i. 405 power of, reduced in chronic tuber- culosis, ii. 393 reflex spasm of, cause of, i. 399 in advanced tuberculosis difficult to detect, i. 467 reflex trophic changes in, i. 400, 466 regional spasm and degeneration of, in diagnosis of pulmonary tuberculosis, i. 410, 466 Muscles — Cont 'd rigidity of, in tuberculous menin- gitis, ii. 90 somatic, segmental innervation of, i. 179, 329 spasm of, shows healing not com- plete, ii. 539 superficial, spasm of, i. 179, 399, 405, 604 Muscular action, effect of, on circula- tion, ii. 402 Muscular element, in respiratory sound, i. 431 N Naegeli, statistics of pulmonary infec- tion in adults, i. Ill, 408; ii. 191 Nausea, in anaphylaxis, ii. 159 in dilatation of stomach, i. 263 in tuberculosis, i. 215, 439 in- tuberculous enteritis, i. 444; ii. 39 Necrosis, not due to pus organisms, i. 48 of vessel causes hemorrhage, ii. 172 Nerve, recurrent laryngeal, in causing hoarseness, i. 386 superior laryngeal, in causing hoarseness, i. 386 Nerve action, selectivity of, i. 220 Nerve cells, act only if impulse is suf- ficient, i. 220 affected differently by helpful and harmful stimuli, ii. 394 changes in, following depressive emotions, i. 43 fatigue of, must be appreciated in treatment, ii. 528 injured by long continued harmful stimuli such as toxins, i. 220, 221 irritability of, in neurasthenia, ii. 398 Nerve control, of blood vessels, i. 232 of gastrointestinal tract, i. 278 of heart, i. 230 of visceral activity, ii. 392 Nerve equilibrium, disturbed by tox- ins, ii. 390 Nerve exhaustion, calls for rest, ii. 294 Nerves, pathological changes in, i. 44 Nervous influences, shown on pulse and temperature, ii. 531 682 INDEX Nervous influences — Cont'd upon temperature curve, ii. 146 Nervous instability, part of syndrome of toxemia, ii. 110 Nervous system, and nutrition, ii. 328 and prognosis, i. 636 and toxemia, i. 151, 158, 189, 217, 366, 612; ii. 527 central, connection of, with vegeta- tive system, i. 170 controls heat loss, ii. 115 Night or sleep sweats, i. 445; ii. 449 cold sponge in, ii. 451 effect of open air on, ii. 451 part of syndrome of toxemia, i. 371; ii. 110 treatment of, ii. 451 vinegar bath in, ii. 451 Nitrites, in treatment of hemorrhage, ii. 178 Non-tuberculous changes, i. 42 Nose, tuberculosis of, i. 46 Nutrition, affected by abnormal, cir- culation, ii. 328 respiratory action, ii. 328 nervous system, ii. 328 as long as patient maintains, out- come hopeful, ii. 550 changes in, in tuberculous enteri- tis, ii. 39 conception of, i. 251 degree of, modifies visceral form, i. 336 in tuberculosis, i. 252 low, calls for rest, ii. 293 maintained on variable diets, ii. 308 relation of body cells to, ii. 327 Nervous system, degenerative diseases of, common in tuberculous families, i. 150 greater vagus, i. 170 importance of understanding rela- tionship to tuberculosis, i. 150, 168, 217, 604 in tuberculous meningitis, ii. 89 i. 150, 168, 217 sympathetic, i. 170 vegetative, i. 169 and anaphylaxis, ii. 157 pathological degeneration in in- ternal viscera, a result of ir- ritation of, i. 606 reflex disturbance of function of internal viscera, due to, i. 199-216, 254 Nervus pelvicus, part of greater vagus system, i. 186 Neumann, on congestive type of hem- orrhage, ii. 175, 180 Neurasthenia, ii. 294, 390 and early clinical tuberculosis, i. 364 and rest, ii. 294 and tuberculosis, i. 158, 612 improved by open air, ii. 248 method of explaining to patient, ii. 528 necessity of hope in, i. 530 treatment of, in tuberculosis, ii. 398 Neuritis, and tuberculosis, i. 161; ii. 456 brachial and tuberculosis, i. 161 in tuberculosis, pathology of, i. 167 of laryngeal nerves, i. 450 Neutrophiles, Arneth 's classification of, i. 577 from pulmonary cavities stain poor- ly, i. 536 nuclear and protoplasmic changes in, i. 577 Newsholm, statistics of mortality by age periods, i. 98 O Occupation, change of, and prognosis, i. 655 Occupational changes in chest mus- cles, i. 333, 405, 413 Ocean voyages, objections to, ii. 266 Old tuberculin (O. T.) (Koch), ii. 354 Open air, ii. 227 a great advance in treatment, ii. 228 and fog, ii. 252 and prognosis, i. 646 and weather conditions, ii. 252 causes greater demand for food, ii. 248 effects of, ii. 248 on non-tuberculous same as on tu- berculous, ii. 229 food and hygiene not cures for tu- berculosis, ii. 203, 227, 252 improves metabolism, ii. 244, 248 increases, patient's resistance, ii. 246 pulmonary ventilation, ii. 239 INDEX 683 Open air — Cont'd individualization in dosage of, ii. 247 judgment necessary in exposing pa- tients to, ii. 247 on what does benefit depend, ii. 229 opposed by many, ii. 228 oxygen not most important factor in, ii. 229 patient's resisting power should be considered in instituting, ii. 249 should be assisted by other meas- ures, ii. 227 wrongly conveys idea of exercise, ii. 252 Open air treatment, technic of, ii. 248 Open tuberculosis, in family, meaning of, in history, i. 362 Organs, displacement of, in tubercu- losis, i. 253 Orth, manner in which trauma acti- vates tuberculosis, i. 314 Ovary, internal secretion of, i. 195 secretion of, effect on temperature, case illustrating, ii. 639 tuberculosis of, ii. 103 tuberculous, healed by tuberculin, ii. 103 Overexertion and hemorrhage, ii. 168 Overfeeding, and indican, i. 587 evil effects of, ii. 310, 313 no excuse for, in early tuberculosis, ii. 312 sometimes permissible, ii. 313 Oxygen, amount necessary for body during rest and exercise, ii. 279 deficency of, causes acidosis, ii, 281, 292 not most important factor in open air, ii. 229 Oxygenation, factors interfering with, case illustrating, ii. 584 Ozone, effect on tuberculosis, ii. 262 Pain, codein and Dover's powder in, ii. 457 due to neuritis in tuberculosis, ii. 456 stretching adhesions, i. 453 heart in treatment of, ii. 457 in pneumothorax, ii. 75 Pain— Cont 'd in shoulders, i, 388, 452 reflex as sign of inflammation in lung, cases illustrating, ii. 580, 608 in tuberculosis of kidney, ii. 98 in tuberculous enteritis, ii. 40 laryngitis, ii. 25 location of, in acute pleurisy, ii. 56 in advanced tuberculosis, i. 452 over chest areas due to inflamma- tion of abdominal organs, i. 455 treatment of, ii. 457 in tuberculous enteritis, case il- lustrating, ii. 648 when cavity forming, i. 453 zones of, in tuberculosis, ii. 456 Pains, chest and shoulder, in tuber- culosis, i. 388, 452 due to reflex trophic changes in nerves, and sensory disturb- - ances, i. 452, 455 Palpation, and percussion, same pro- cedure, i. 414 deep, cases illustrating, ii. 525, 535, 543, 555, 567, 580, 610, 622, 633, 651 detecting enlarged Ivmphatic glands by, i. 410, 417 infiltrations, cavity, emphysema, thickened pleura, effusions, mediastinal thickening and outline of organs by, i. 410 tactile fremitus by, i. 410, 417 determining, activity of pulmonary process by, i. 472 compensatory emphysema by, i. 472 condition of muscles, skin and subcutaneous tissues by, i. 410, 472, 473 density of tissues, i. 473, 476 movement of chest wall, i. 468, 472 nature of infiltration, i. 413, 472, 484 pathological process in lung, i. 472 pleural adhesions, i. 472 presence of pleurisy, i. 472, 496 cavity, i. 472, 490 shifting of diaphragm, i. 472 mediastinum, i. 472 factors causing change in, i. 397 684 INDEX Palpation — Cont 'd importance of soft tissues in, shown by thickness of, i. 332 in advanced tuberculosis, i. 472 in compensatory emphysema, i. 495 in mediastinal glands, i. 115, 500 in pneumothorax, ii. 79 in thickened pleura, i. 497 lagging detected by, i. 403, 410, 416 light touch, value of, i. 411 of deep tissues, suggestion for be- ginners, i. 424 of great value in diagnosis, i. 416, 472 what can be determined by, in pul- monary lesions, i. 409 Park, shows relative percentage of bovine and human infection, i. 58 Partial antigens, Koch's O. T. con- tains greatest number of, i. 506 Past illness, importance of in clin- ical history, i. 364 Paterson, graduated exercise, ii. 301 Pathological changes, character of, i. 25 Patient, co-operation of, depends on attitude of physician, ii. 212 essential to cure, i. 642 ; ii. 211 ease illustrating, ii. 538 difficulty of, obtaining diagnosis, case illustrating, ii. 558, 582 effect of hope on, ii. 391 feeding of, ii. 492 haphazard treatment of, proves dis- astrous, case illustrating, ii. 636 helped to cure self by psycho- therapy, ii. 389 hope required by, for co-operation, ii. 395 how inform, of presence of tuber- culosis, ii. 397 how often shall physician see, ii. 480 if ignorant, fails to cooperate, ii. 219 importance of resisting power in, ii. 508 improves in spite of extensive and active disease, case illustrat- ing, ii. 575 indifference and laziness of, ii. 301 Patient — Cont 'd must be candid with physician, ii. 210 cooperate with physician, ii. 217 follow program, ii. 476 neglected while disease is empha- sized, ii. 388 nervous, unwise to find fault with, ii. 399 personal hygiene of, ii. 512 reactive powers of, to bath, vary with conditions, ii. 406 relationship of, to physician, ii. 208 relieved by knowing diagnosis, ii. 215 sanitary arrangement of room for, ii. 510 should know he has tuberculosis, ii. 213 training of, important, ii. 475 tuberculous, requires close medical guidance, ii. 223 Patients, choice of, for sanatorium, ii. 495 importance of lecturing to, ii. 221 Patton, Noel, internal secretions, i. 69 Pearson and artificial immunization, ■ ii. 335 Pectoralis, innervation of, i. 296, 328, 331 Percussion, all muscles relaxed during, i. 419 common errors in, i. 419 condition of muscles and subcutan- eous tissue alters data found on, i. 477 factors causing changes in, i. 397 gives no evidence of activity, i. 426 importance of soft tissues in, shown by thicknes of, i. 332 important muscles which affect, i. 419 in advanced tuberculosis, i. 477 in compensatory emphysema, i. 495 in diagnosis, i. 417 in dry pleurisy, i. 496 in early active tuberculosis, case il- lustrating, ii. 526 in extensive fibro-ulcerative tuber- culosis, cases illustrating, ii. 544, 555, 568, 581, 610, 622, 634, 652 in mediastinal thickening, i. 500 INDEX 685 Percussion — Cont 'd in moderately advanced active tu- berculosis, case illustrating, ii. 535 in pleural effusion, i. 496 in pneumothorax, ii. 79 in pulmonary cavity, i. 490 fibrosis, i. 489 infiltration, i. 485 light or heavy, i. 417 light stroke felt through chest, i. 418 Percussion changes, in chronic focus again active in one lung, and new active focus in other, i. 424 in early pulmonary tuberculosis, i. 420 in healed focus in one apex, and active focus in other, i. 423 in primary active lesion in one apex, i. 421 in quiescent or healed lesion in one apex, i. 421 Percussion findings, in old focus with renewed activity in one apex, i. 423 Percussion note, altered by conditions within chest, i. 425 Pericarditis, complicating pulmonary tuberculosis, case illustrat- ing, ii. 602 tuberculous, pathology of, i. 49 Percardium, displacement of heart de- pends on size of, i. 286 case illustrating, ii. 598 Peripheral nerves and tuberculosis, i. 160, 167 Peristalsis, effect of emotions on, i. 279 Peritonitis, tuberculous, pathology of, i. 50 Perlsucht, Emulsion (P. E.) Spengler, ii. 356 Tuberculin (P. T. O.) Spengler, ii. 355 Vaccine, Spengler, ii. 355 Perspiration in anaphylaxis, ii. 160 Petroff's method of sputum culture, i. 560 Petruschky's "Etappen Method" of using tuberculin, ii. 383 Pharynx, reflex motor and sensory disturbances in, i. 214 tuberculosis of, i. 46; ii. 105 Pharmacological remedies, and prog- nosis, i. 654 in treatment of tuberculosis, ii. 461 Phillipi, statistics of psychoneuroses, i. 158 Phillip's fermentation method of ex- amining sputum, i. 553 Phrenics, degenerative changes in, i. 167 reflex spasm of, causes lagging, i. 403, 468 reflex stimulation of, from lung, i. 403, 468 Phthisical chest, i. 464 Phthisiophobia, ii. 490, 520 spread by physicians, ii. 521 Physical signs, etiological classifica- tion of, in early pulmonary tuberculosis, i. 394 of advanced pulmonary tuberculo- sis, i. 435 Physical types, normal variation in, i. OoS } ooO Physician, attitude of, towards pa- tient, ii. 222 confidence in methods of, aids, ii. 395 how often see tuberculous patient, ii. 480 in relationship to prognosis, i. 641 must be candid with patient, ii. 210 must cooperate with patient, ii. 217 optimism of, aids in cure, ii. 206 relationship of, to patient, ii. 208 Physiological adaptation, man's power of, ii. 257 to altitude, ii. 259 to climatic changes, ii. 258 to different degrees of moisture and altitude, ii. 273 Physiological basis, of psychotherapy, ii. 392 Physiological facts important in chest examination, i. 319 Pike, effect of low blood pressure, I. 237 mechanisms involved in maintaining blood pressure, i. 236 Pilomotor muscles supplied by sym- pathetics, i. 176 Pituitrin in treatment of hemorrhage, ii. 178 Playgrounds in preventing tuberculo- sis, ii. 515 Pleura, absorptive power of, ii. 53 cough from, i. 451 686 INDEX Pleura — Cont 'd thickening of, i. 497 diagnosed by palpation, cases il- lustrating, ii. 555, 568 Pleural adhesions, ii. 59 description of changes in soft tis- sues over, ii. 59, 60 Pleural effusion, in advanced tubercu- losis, i. 496 in artificial pneumothorax, ii. 439 may follow pneumothorax, ii. 84 Pleurisy, acute fibrinous, ii. 53 cough in, ii. 54 pain in, ii. 54 acute serofibrinous, ii. 54 diagnosis of, ii. 57 dyspnea in, ii. 57 pain in, ii. 56 treatment of, ii. 49 apical, many cause no pain, ii. 49 as early symptom of tuberculosis, i. 391 ; ii. 58 cases illustrating, ii. 536, 553, 557, 559, 590, 596, 612, 632, 659 auscultation in, ii. 58 complicating pulmonary infection, ii. 52 diaphragmatic, ii. 67 abdominal pain in, ii. 69 neck pain in, ii. 70 referred pain in, ii. 67 spasm of muscles in, i. 455 dry, in advanced tuberculosis, i. 496 early, means active tuberculosis, ii. 50 effusion in, shall it be removed, ii. 58 in advanced tuberculosis, i. 460 infection in, ii. 50 inspection in, ii. 57 makes diagnosis almost certain, i. 607 may come any time prior to heal- ing, ii. 564 palpation in, ii. 57 pathological changes in intercostal muscles in, ii. 61 percussion in, ii. 58 preceding definite clinical pulmo- nary tuberculosis, ii. 49 pathology of, i. 48 wrongly diagnosed intercostal neu- ralgia, ii. 49 Pleuritis, tuberculous, ii. 49 Pneumonia, a definite air-borne dis- ease differs from tubercu- losis, i. 67 acute caseous, case illustrating, ii. 628 caseous, temperature curve of, ii. 133 caused by hemorrhage, ii. 177, 183 differentiated from tuberculosis, i. 67 artificial, ii. 429 amount of gas injected in, ii. 436 and compensatory emphysema, ii. 431 beneficial effects of, ii. 433 complications of, ii. 439 conditions not always same when performed, ii. 430 effect in compressing lung, ii. 430 effects produced by, ii. 307 gas embolism in, ii. 441 in treatment of hemorrhage, i. 653, ii. 180 indications for, ii. 442 injury to lung in, ii. 441 length of treatment with, ii. 437 lessens danger of spread of dis- ease, ii. 433 lights up activity in the lung, ii. 440 pleural effusion in, ii. 439 results of treatment with, ii. 443 site of puncture for, ii. 435 technic, ii. 434 auscultation, ii. 81 bulging of intercostal spaces in, ii. 80 cause of, ii. 74 changes in position of diaphragm in, ii. 79 coin sound in, ii. 81 cough in, ii. 78 dangers of, ii. 83 diagnosis of, ii. 81 diet in, ii. 87 difficulties of diagnosis in, ii. 82 difficult of diagnosis when patient not previously under observa- tion, ii. 73 does not depend on strain, ii. 74 dyspnea in, ii. 75 effect on patient, ii. 73 sputum, case illustrating, ii, 615 emphysema of superficial structures in, ii. 441 INDEX 687 Pneumonia — Cont 'd follows necrosis of tubercle near pleura, case illustrating, ii. 615 heart in, ii. 78 increases respiratory effort, ii. 432 inspection, palpation and percus- sion in, ii. 79 loss of consciousness in, ii. 79 may relieve toxemia, ii. 83 may result in benefit or harm, ii. 83 metallic tinkling in, ii. 81 morphine in, ii. 87 offers argument against mixed in- fection, ii. 83 often undiagnosed, ii. 73 pain in, ii. 75 pain not constant symptom in, ii. 74 pleural effusion in, ii. 84 prognosis in, i. 633 recurrent, cases illustrating, ii. 85 relief of symptoms following, case illustrating, ii. 615 rest in, ii. 87 shifting of mediastinum in, ii. 79 spontaneous, cases illustrating, ii. 574, 578 sputum in, ii. 79 succussion sound in, ii. 81 sudden rise of temperature and pulse curves in, ii. 82 symptoms of, ii. 74 cases illustrating, ii. 615, 629 in spontaneous and artificial, dif- fer, ii. 438 temperature in, ii. 75 treatment of, ii. 87 case illustrating, ii. 630 varieties of, ii. 82 vocal fremitus in, ii. 80 x-ray in, ii. 81 Posture, effect on temperature, ii. 154 Pratt, class work of, in tuberculosis, ii. 221 Predisposition to tuberculosis, i. 117 Pregnancy, effect on, prognosis, i. 640 tuberculosis, ii. 623 case illustrating, ii. 553 Premenstrual rise in temperature, i. 378; ii. 149 Present illness and clinical history, i. 365 Prognosis, acute caseous tuberculosis, in, i. 630 age in, i. 624 bacilli, form of, in, i. 634 presence of, in, i. 633 blood, condition of, in, i. 639 change of occupation in, i. 655 character of lesion in, i. 628 treatment in, i. 641, 644 chronic ulcerative tuberculosis In, i. 629 circulatory system in, i. 638 climate in, i. 647 constitution in, i. 625 diazo reaction in, i. 639 digestive system in, i. 637 earliness of, diagnosis in, i. 642 treatment in, i. 642 economic status in, i. 626 environment in, i. 626 fibroid tuberculosis in, i. 629 food in, i. 649 heliotherapy in, i. 648 hydrotherapy in, i. 649 in pulmonary tuberculosis, i. 624 induced pneumothorax in, i. 653 mental state in, i. 628 miliary tuberculosis in, i. 628 nervous system, condition of, in, i. 636 non-tuberculous complications in, i. 636 open air in, i. 646 patient, cooperation of, in, i. 642 pharmacological remedies in, i. 654 physician, importance of, in, i. 641 pleurisy in, i. 632 pneumothorax in, i. 633 pregnancy in, i. 640 psychotherapy in, i. 651 respiratory system in, i. 636 rest and exercise in, i. 650 sanatorium vs. home treatment in, i. 645 tuberculin in, i. 652 tuberculin reaction in, i. 635 tuberculosis of intestines in, i. 632 tuberculosis of larynx in, i. 631 tuberculous complications in, i. 631 tuberculous meningitis in, i. 633 urochromogen reaction in, i. 639 Program, for home treatment, ii. 476 for sanatorium treatment, ii. 500 Prophylaxis, ii. 503 Prostate, tuberculosis of, ii. 103 688 INDEX Protargol in laryngeal and pharyn- geal irritation, ii. 448 Protein, an important element of diet, ii. 309 Protein, baeillary, in the production of fever, ii. 122 discussion of fever caused by, ii. 118 from whatever source produces same toxic syndrome, ii. 342 in causation of fever, ii. 114, 116 may be followed by either toxemia of anaphylaxis, ii. 161 peripheral irritation of vagus by, causes asthma, ii. 165 symptoms from, produced by small- er dose in sensitized than in non-sensitized animals, ii. 344 Protein poisoning, caused by contam- ination of distilled water, ii. 179 Psychasthenia, ii. 390 Psychoneuroses, i. 151, 158 Psychoses, i. 150 pathology of, i. 159 Psychotherapy, ii, 387 a positive optimism, ii. 388 acts by improving general resist- ance, ii. 395 an individual therapy, ii. 390 applied to tuberculosis, ii. 392 for poor eaters, ii. 400 helps patient cure self, ii. 389 importance of, in treatment of tu- berculosis, ii. 206 improves, appetite, ii. 394 digestion, ii. 394 prognosis, i. 651 most generally applicable of all remedies to chronic tubercu- losis, ii, 394 physiological basis for, ii. 392 presupposes analyzing each patient, ii. 391 relieves effects of depressive emo- tions, ii. 389 relieves inhibitory action of sym- pathetics, ii. 394 technic of application in tubercu- losis, ii. 396 treats patient as individual, ii. 388 Pulmonary tissue especially adapted to the tubercle bacillus, i. 122 Pulmonary tuberculosis, percentage of bovine and human infection in, i. 59 prognosis in, i. 624 Pupil, dilatation of, in pulmonary tuberculosis, i. 402 sympathetic and greater vagus ac- tion on, i. 198 Pulse, acceleration of, during toxemia in early tuberculosis, i, 381 character of, in tuberculosis, i. 230 effect of vagus stimulation on, case illustrating, ii. 646 in tuberculous enteritis, ii. 42 persistently rapid, i. 443 rapid, explanation of, i. 231 slowed by intestinal infection, case illustrating, ii. 618, 658 slowing of, due to reflex stimula- tion of vagus, ease illustrat- ing, ii. 654 following use of tuberculin, case illustrating, ii. 548 Pyogenic organisms, not cause of ne- crosis, i. 48 E Rain, and open air, ii. 252 Rales, crepitant, i. 480 decrease of, as healing takes place, i. 481 extrapulmonary, i. 482 localized over areas of softening, i. 481 Ranke, divides tuberculosis into three stages, i. 357 Ravenel, feeding experiments, i. 69 historical sketch of ingestion tu- berculosis, i. 75 Reaction, after baths, ii. 406 immunity, tuberculin an, i. 503 prompt maximum means active le- sion, i. 601 tuberculin, ii. 336 focal, ii. 340 not excessive in advanced tu- berculosis, ii. 350 general, ii. 337 local, ii. 338 Recovery, slow, from other diseases, i. 365 Reflex, cause of asthma, ii, 164 kidney, motor and sensory, ii. 99 motor from lung, i. 454 motor to diaphragm, i. 403 INDEX 689 Reflex— Cont'd motor, in tuberculous enteritis, ii. 43 sensory, in tuberculous enteritis, ii. 43 path, of, i. 454 Reflex changes, in soft tissues, re- gional in character, i. 44, 399, 405, 412, 467, 473; ii. 525 Reflex muscle changes due to patho- logical degeneration and oc- cupation, i. 333, 405, 413, 475 Reflex pathological changes, in chest muscles, i. 44, 406 Reflex spasm, and degeneration in di- agnosis, i. 399, 466 of muscles difficult to detect at times, i. 467 Reflex stimulation, early symptoms of pulmonary tuberculosis due to, i. 366, 384 symptoms of, in advanced tuber- culosis, i. 437 to 456 Reflexes, from surface to viscera and vice versa, ii. 401 Remedies, pharmacological in hemor- rhage, ii. 177 Resistance, decrease in, favors clin- ical disease, ii. 199 general, improved by psychother- apy, ii. 395 improvement in, important thera- peutic principles, ii. 200, 508 low, at time of puberty, ii. 199 Respiration, and nutrition, ii. 328 combined thoracic and abdominal types of, i. 300 diaphragmatic type of, i. 299, 325 muscles involved in, i. 296, 324, 327 obstructed, in tuberculous laryn- gitis, ii. 26 thoracic type of, i. 298 Respiratory compensation, in new born, i, 128 Respiratory effort, increased by pneu- mothorax, ii. 432 Respiratory note, conditions affecting, i. 429 effect of muscles and subcutaneous tissue on, i. 428 in early tuberculosis, i. 429 Respiratory sounds, character of, in early tuberculosis, i. 610 Respiratory sounds — Cont 'd quality of, in advanced tuberculosis, i. 479 why and how differ in early pul- monary tuberculosis, i. 432 Respiratory system, and prognosis, i. 636 changes in, in advanced tubercu- losis, i. 478 Rest, and exercise in prognosis, i. 650 during fever, ii. 285 during hemoptysis, ii. 288 effect of, upon cough, ii. 291 upon the heart, ii. 289 on symptoms, case illustrating, ii. 627 on temperature, ii. 287 essential to life, ii. 283 few people know how to, ii. 304 for lung, ii. 204 important in treating every case of tuberculosis, ii. 285, 296 in early afebrile tuberculosis, ii. ' 284 in neurasthenia, ii. 530 in pneumothorax, ii. 87 in treatment, of fever, ii. 454 of tuberculosis, i. 265; ii. 277, 282 case illustrating, ii. 538, 545, 604 may not produce desired results, ii. 287 mental, in hemorrhage, ii. 176 physical, in hemorrhage, ii. 177 physiology of, ii. 281 relieves the patient of large de- mands, ii. 284 to lung, decreases toxemia, ii. 307 produced by artificial pneumo- . thorax, ii. 307 toxins disappear during, ii. 530 when dyspnea is present, ii. 292 when nerve exhaustion is present, ii. 294 when nutrition is low, ii. 293 Rest hour, ii. 203 Rhomboidei, innervation of, i. 296, 328, 331 Ribs, inclination of, at different age periods, i. 128 Richard, mechanical shaker for spu- tum, i. 554 Right-handedness, and muscle degen- eration, i. 405, 475 690 INDEX Rigidity of muscles in tuberculous meningitis, ii. 90 Riviere and Morland's method of tu- berculin dosage, ii. 361 Roger, method of studying albumin reaction in sputum, i. 538 Rollier, popularizes heliotherapy, ii. 422 Romer, and tuberculin hypersensitive- ness, i. 506 and tuberculin reaction, ii. 336 incubation period in tuberculosis, i. 65 Room, sanitary arrangements of, ii. 510 should be sunny, ii. 511 Rosenow, shows bacteria grown on one tissue favors same in next infection, i. 32 Ross, emphasizes sensory disturbance of skin, i. 454 Rothschild's theory of diminution of manubriosternal angle, i. 133 ' ' Roughing it ' ' not best form of out- door life, ii. 299 Route of entry of the tubercle bacillus, practical importance of its solution, i. 30 Russell, studies on open air, ii. 230 S Sahli, congestive type of hemorrhage, ii. 175 Sajous, Chas. E. de M., Internal se- cretions, i. 169 Saliva, sympathetic and greater vagus action on, i. 211 Salt solution, concentrated, in treat- ment of hemorrhage, ii. 179 Sanatoria, more needed, ii. 489 undermanned, ii. 486 Sanatorium, advantages and disad- vantages of, ii. 481, 486, 490 adverse criticism of, ii. 485 attendants do not become infected, ii. 519 choice of patients for, ii. 495 difficulty of feeding patients in, ii. 492 no danger of infection in, ii. 493 results of treatment in, ii. 493 sea side, for children, ii. 267 should have an efficient head, ii. 487 should not treat en masse, ii. 487 Sanatorium treatment, ii. 481 and prognosis, i. 645 contraindications for, ii. 497 cost of, ii. 488 length of, ii. 498 program for, ii. 500 Satterthwaite, effect of toxemia on heart muscles, i. 245 Saugmann, length of pneumothorax treatment, ii. 437 Scaleni, in diagnosis of pulmonary tuberculosis, i. 401 innervation of, i. 296, 327, 331 Scapula, altered position of, i. 471 Schafer, endocrine organs, i. 169 Schmorl's theory of apical furrow, i. 133 Schools in prevention of tuberculosis, ii. 515 Scrofula, i. 108 Sea air, and tuberculosis, ii. 265 free from contamination, ii. 266 Season influences, in treatment of tu- berculosis, ii. 273 Sediment, volume in sputum, study of, i. 537 Segmental innervation, of somatic muscles, i. 329 Segmental relationship, of lungs, i. 179 Segmentation, of body, importance of understanding, i. 177 Seminal vesicles, tuberculosis of, ii. 103 Sensitization, cell, degree of, deter- mined by character of tuber- culin reaction, i. 504 effects implantation, i. 34, 119 of body cells to tuberculin, a per- ipheral nerve stimulation, ii. 342 of cells, and infection, i. 34, 64, 82, 89, 112; ii. 337 prevents metastases, i. 120; ii. 198 Sensory reflex from lung, path of, i. 454 Sewall, auscultation of whispered voice, i. 434 discussion of climate, ii. 255 relationship of short bacilli to ac- tivity, i. 634 Shadow, normal hilus and trunk, in x-ray plate, i. 521 Shadows, trunk, caused by blood ves- sels or bronchi, i. 522 INDEX 691 Shell fish poisoning, due to anaphy- laxis, i. 157, 161 Sherrington, intergrative action of nervous system, i. 169 Shock, following hemorrhage, ii. 184 Shoulders, drooping of, i. 471 pain in, as symptom of intrapul- monary disease, i. 388, 452 Skeletal architecture, variation in, i. 335 Skin, areas showing sensory changes, from lung, i. 454 atrophy of, in advanced tubercu- losis, i. 466; ii. 403 blotching and itching of, in ana- phylaxis, ii. 160 infection through, i. 80 light stimulates, ii. 418 mechanical stimulation of, in bath, ii. 408 most body heat eliminated through, ii. Ill pathological changes in, i. 44 regulates heat loss, ii. 403 should be active in tuberculosis, ii. 403 stimulation of, influences blood and lymph flow, ii. 402 Sleep, ideal physiological rest, ii. 281 improved by open air, ii. 248 Smegma, differentiated from tubercle bacilli, i. 559 Smith, Archibald, initiates altitude treatment of tuberculosis, i. 647 Theobald, and question of inter- transmissibility of bacilli, i. 57 Soiland, Albert, comparative interpre- tation of x-ray plates and physical diagnosis, i. 526 Solly, discussion of climate, ii. 254 Spasm, of abdominal muscles in tu- berculous enteritis, ii. 43 of chest and neck muscles in ac- tive tuberculosis, i. 179, 332, 398, 410, 466 of intercostal muscles in acute pleu- risy, i. 496; ii. 59 of lumbar muscles in tuberculosis of kidney, ii. 98 Specific cellular defense and infec- tion, i. 89 Spengler, and artificial immunization, ii. 335 Spengler — Cont 'd suggests use of bovine tuberculin, ii. 356 Spengler 's method of designating dosage of tuberculin, ii. 361 staining for bacilli, i. 557 Sphincter muscles, innervation of, i. 176 Sphincters, in anaphylaxis, ii. 160 Spinal fluid, in tuberculous menin- gitis, ii. 91 Splanchnic congestion, cause of, i. 303 in advanced tuberculosis, i. 303, 439 in tuberculosis, ii. 290 Spleen, tuberculosis of, i. 54 Sponge, cold, ii. 407 Spray bath, ii. 409 Sputum, absence of, though cavity present, ii. 557 albumin reaction, diagnostic value of, i. 582 in, i. 538 method of determining, i. 539 amounts of, vary from day to day, i. 534 antiformin method of examining, i. 556 as early symptom of tuberculosis, i. 392 bacilli, disappearance from, i. 582 free and bunched in, study of, i. 545 bacilli in, take stain differently, i. 542 care of, in home, ii. 477 collection of, i. 534 cytological examination of, i. 536 daily variation in bacilli in, when numbers low, i. 549 dangers from dried, i. 563 decreases following pneumothorax, case illustrating, ii. 615 direct smear, method of preparing, i. 552 distribution of bacilli in, i. 540 Ellermann and Erlandsen, technic for examination of, i. 551 examination of, for bacilli, stand- ardization of, i. 541 in diagnosis of pulmonary tuber- culosis, i. 534 factors causing amounts of, to vary, i. 459 fermentation of, prior to examina- tion, i. 537, 553 692 INDEX Sputum — Cont 'd from cavity, slow to disappear, ii. 564 Gram-positive, but non-acid-fast- forms in, i. 559 homogenization of, value of, i. 552 importance of examining, i. 458 in advanced tuberculosis, i. 458 in early diagnosis of tuberculosis, i. 607 in pneumothorax, ii. 79 lymphocyte count, diagnostic value of, i. 582 mechanical shaker, in examination of, i. 554 Much's granules in, i. 559 mucus in, method of removing, i. 539 number of bacilli in, in 24 hours, i. 561 sediment volume, directions for de- termining, i, 537 error in method, i. 538 value of study of, i. 537, 591 should always be examined, ii. 214 staining for bacilli, i. 556 straining for cytological examina- tion of, i. 536 swallowing of, when not raised, i. 459 technic for preparation of, for ex- amination, i. 549 time of search for bacilli, impor- tant, i. 540, 543 twenty-four hour sample of, advan- tage of, i. 534 wet method of preparing for ex- amination, i. 556 Stain, factors interfering with bacilli taking, i. 541 Staining, advantages of Spengler's method, i. 558 Stains, for bacilli, i. 556 Starling, showing normal elimination of body heat, ii. Ill Stasis, intestinal, factors operating to cause, in tuberculosis, i. 268 ill effects of, upon patient, i. 268 in tuberculosis, i. 266 treatment of, i. 268 normal points of, in intestine, i. 267 State, part of, in preventing tuber- culosis, ii. 514 Statistics, of different observers not comparable, ii. 386 Steinert, reports degeneration in as- ' cending fibers of cord, i. 167 Sternocleidomastoideus, in diagnosis of pulmonary tuberculosis, i. 401 innervation of, i. 296, 327, 330 Sthenic type of individual, character- istics of, i. 349, 354 Stethoscope, i. 427 Stomach, atony and dilatation of, in tuberculosis, i. 258, 262 dilatation of, case illustrating, ii. 618 symptoms of, i. 263 symptoms accompanying, case il- lustrating, ii. 647 treatment of, i. 263 case illustrating, ii. 647 disturbances of, in tuberculosis, i. 257 reflexly stimulated by inflammation of lung, i. 215 sympathetic and vagus action on, a. 215 Stool, bacilli in, i. 52 in tuberculous enteritis, ii. 41 Strength, loss of, in advanced tuber- culosis, i. 438 part of syndrome of toxemia, ii. 110. Streptothricosis, differentiated from tuberculosis, i. 621 Stricture in tuberculous enteritis, ii. 38 Subcutaneous tissue, condition of, al- ters palpation, i. 398 alters percussion, i. 398 degeneration of, cause of, i. 399 in advanced tuberculosis, i. 466 in chronic tuberculosis, case il- lustrating, ii. 525, 535, 543, 554, 567, 580, 610, 622, 633 lowers percussion note and de- creases resistance, i. 477 effect of occupation on, i. 333, 406 influence on physical findings, i. 332 regional degeneration of, means chronicity, i. 399, 405, 466, 473 Suggestion in treatment, i. 156 (see Psychotherapy) Sulci, pulmonary, position of, i. 321 Sun, physical condition of, ii. 414 Superinfection, i. 359 INDEX 693 Suspiciousness of tuberculous pa- tients, i. 157 Sweat glands, muscles of, supplied by sympathetics, i. 176 Sweating, a result of toxemia, i. 371, 445 ; ii. 450 part of syndrome of toxemia, ii. 110 part of vagus syndrome, i. 371, 445 Sweats, night or sleep, ii. 449 night, treatment of, ii. 451 Swimming, followed by hemorrhage, ii. 300 not permitted in tuberculosis, ii. 300, 410 Sympathetic inhibition, relieved by psychotherapy, ii. 394 Sympathetic nervous system, i. 170 Sympathetic reflex, due to peripheral irritation, i. 604 Sympathetic system and ovarian se- cretion, i. 195 grouping of structures supplied by, i. 175 peculiarities of, i. 170, 172 Sympathetics, action of, upon heart, i. 230 and digestive tract, i. 254 central stimulation of, produces toxic group of symptoms, i. 231, 604 characteristics of action of, i. 227 conditions which irritate in tuber- culosis, i. 223 effect on digestive tract, i. 440 heart and blood vessels, i. 175, 199, 232; ii. 110, 551 in the production of temperature, ii. 116 stimulation of, causes syndrome of toxemia, ii. 110 supplying lung, i. 180 Symptoms, absence of, does not mean pathological healing, ii. 564 blood spitting, in classification of, ii. 169 cessation of, not synonymous with healing, ii, 194 classification of, cases illustrating, ii. 525, 534 clinical, of early tuberculosis, i. 357 depend on vagus nerve tonus of in- dividual, ii. 161 Symptoms — Cont 'd difference in early and advanced pulmonary tuberculosis, i. 435 do not indicate seriousness of in- fection, case illustrating, ii. 607 due to, antagonistic action of greater vagus and sympa- thetic systems, i. 199 depressive emotions, i. 189 reflex stimulation, i. 226, 366, 384 cases illustrating, ii. 525, 527, 543, 567, 609, 621, 650, 659 toxemia, i. 226, 366; ii. 110 cases illustrating, ii. 537, 609, 621, 631, 650, 659 variable, i. 368 tuberculous process per se, i. 226, 366, 390 most valuable in diagnosis, i. 606; ii. 537 early, etiological classification of, i. 365 etiological classification of, i. 184 case illustrating, ii. 525, 534, 543, 554, 567, 591, 600, 610, 622, 632, 651 etiological classification of, gives better understanding of clin- ical disease, i. 604 illustrated, i. 527, 528, 530 influenced by internal secretions, i. 194 in spontaneous and artificial pneu- mothorax, differ, ii. 438 lightness of, not in keeping with severity of case, ii. 538 no, pathognomonic of tuberculosis, i. 598 of activity do not mean unfavor- able progress, case illustrat- ing, ii. 549 of advanced pulmonary tubercu- losis, i. 435 etiological classification of, i. 436 of deficiency in inspiratory act, i. 303 of failing heart, i. 248 of malignant tumors of lung, i. 621 of pneumothorax, cases illustrating, ii. 615, 629 of reflex origin, not constant, i. 385 694 INDEX Symptoms — Cont 'd of toxemia, first group to disap- pear, case illustrating, ii. 564 may disappear early, ease illus- trating, ii. 607 of toxic group, characteristic of, i. 366 importance of, i. 605 of toxic origin, dut to central stim- ulation of sympathetica, i. 604 of tuberculous enteritis, ii. 39 case illustrating, ii. 660 not pathognomonic, case illus- trating, ii. 644, 657 of tuberculous laryngitis, ii. 24 of tuberculous meningitis, ii. 89 part of mechanism of defense, i. 217 reflex, do not disappear early, case illustrating, ii. 607 reflex, point away from lung, i. 384 variable in character, i. 606 relationship of, to greater vagus and sympathetic systems, i. 183 relative value of different groups in early diagnosis, i. 393, 603 relief of, following necrosis and caseation, case illustrating, ii. 628 toxic group of, absence of, does not mean absence of activity, i. 606 conditions under which present, i. 605 toxic, prolonged by adrenin, i. 605 treatment of, ii. 445 unrecognized when metastases tak- ing place, ii. 545 variability of, when vegetative nerves are concerned, i. 176, 187, 189, 385 variable, in advanced pulmonary tuberculosis, i. 435 Syndrome, of anaphylaxis, ii. 159 of toxemia, i. 221, 226 ; ii. 110, 159 and anaphylaxis contrasted, ii. 344 and general tuberculin reaction, ii. 342 prolonged by wrong living, i. 367 Syphilis, pulmonary, differentiated from tuberculosis, i. 618 T Tactile fermitus, meaning of, i. 417 Technic, for preparation of sputum for examination, i. 551 importance of, in applying meas- ures in treatment of tuber- culosis, ii. 205 of applying, exercise, ii. 295 heliotherapy, ii. 423 hydrotherapy, ii. 404 open air treatment, ii. 248 psychotherapy, ii. 396, 398 Temperature, and tuberculin test, i. 507 atmospheric, influence of, on body, ii. 115, 143, 258, 275 body, effect of, humidity on, ii. 143 wind movement on, ii. 143 normal regulation of, ii. 110 case illustrating gradual reduction of, ii. 547 characteristics of, during toxemia, i. 371 differs on two sides of mouth, ii. 155 diurnal variation, increased in in- testinal infection, case illus- trating, ii. 646 diurnal variation in, in tuberculosis, ii. 125 due to inflammation of lung tissue, i. 392 early morning, value of, ii. 127 effect of, cough on, case illustrat- ing, ii. 645 ovarian secretion on, case illus- trating, ii. 639 rest on, case illustrating, ii. 604 elevation of, during increased activ- ity, ii. 572 in relation to tuberculin, case il- lustrating, ii. 642 exercise must not depend upon de- gree of, ii. 297 factors influencing taking of, ii. 125 how long hold theromometer in tak- ing, i. 376, 378 importance of early morning, i. 376 in acute caseous pneumonia, case il- lustrating, ii. 628 INDEX 695 Temperature — Cont 'd in pneumothorax, ii. 75 in tuberculous, enteritis, ii. 42 meningitis, ii. 89 patient, easily influenced, ii. 123 increased by coughing, ii. 573 increased diurnal variation in, ii. 550 due to increased toxemia, case il- lustrating, ii. 639 indicative of moderately active tu- berculosis, case illustrating, ii. 636 instructions for taking, i. 376, 508 ii. 124 large meal raises, ii. 115 marked rises in, caused by cough, case illustrating, ii. 616 maximum and minimum, keep pace with body activities, ii. 109 muscular exercises raises, ii. 115 nervous influences in, i. 380 normal diurnal variation in, ii. 125 pneumonic type of, ii. 550 premenstrual, menstrual, and post- menstrual, i. 378, 380 ; ii. 149 rise in, during toxemia, i. 371 slight persistent rises in, not always due to tuberculosis, i. 381 subnormal, cause of, ii. 121 part of syndrome of toxemia, ii. 110 sudden rise of, in pneumothorax, ii. 82 value of, in early diagnosis, i. 607 wide diurnal variation in, as result of intestinal infection, case illustrating, ii. 655 shows marked vasomotor disturb- ances, ii. 646 Temperature curve, always above nor- mal for time of day, case il- lustrating, ii. 636 and nervous influences, ii. 146 and toxemia, ii. 142 characteristics of, in tuberculin re- action, i. 512 effect of exercise on, ii. 148 effect of menstruation on, case il- lustrating, ii. 559 factors influencing, ii. 154 in chronic fibro-ulcerative tubercu- losis, ii. 129 in tuberculosis, factors affecting, ii. 124 Temperature curve — Cont 'd influenced by, complications, ii. 146 gastrointestinal disturbances, ii. 146 other factors than toxemia, ii. 142 menstrual, influenced by pelvic in- flammation, case illustrating, ii. 637 of acute miliary tuberculosis, ii. 128 of caseous pneumonia, ii. 133 of chronic fibro-ulcerative tuber- culosis, case illustrating, ii. 640 of early tuberculosis, ii. 126 of inactive tuberculosis, ii. 139 of intermittent toxemia, ii. 133 of severe toxemia, ii. 138 valuable, in giving idea of type of toxemia, i. 373 waves in, due to activity, case illus- trating, ii. 614 Temperature fall in, in anaphylaxis, ii. 160 Temperature measurements, accuracy in, essential, ii. 124 Tendeloo 's law, i. 146 Tendeloo 's theory that lessened mo- tion is determining factor in localizing pulmonary metas- tases, i. 135 Testicle, tuberculosis of, ii. 102 diagnosis of, ii. 102 treatment of, ii. 102 Thelinius' method of using mechan- ical shaker, i. 555 Therapeutics, principles underlying, ii. 186 Thoracic cavity, compensatory changes in, i. 281 Thoracic organs, compensation in, i. 281 Thorax, bony, compensation in, i. 293 phthisicus, not a predisposing condi- tion, i. 142 Throat compress, in tuberculous laryn- gitis, ii. 411 Thyroid, enlargement of, in early tu- berculosis, i. 194 Thyroid secretion, influence of, i. 194 Tissue wasting, effects of, i. 306 Tissues, adaptability of, factor in in- fection, i. 31 density of, determined by palpation, i. 476 696 INDEX Tissues — Cont 'd lack of resistance of, on palpation over cavity, i. 490 Tongue, atrophy of, in tuberculosis', i. 214 tuberculosis of, ii. 104 treated by tuberculin, ii. 385 Tonsils, as portals of entry, i. 73 contain tubercle bacilli, i. 73 faucial and pharyngeal, importance of, in defense of child, i. 93 natural drainage of, i. 95 tuberculosis of, i. 46 Tonus, muscular, normal variation in, i. 336 sympathetic, predominates, i. 193 vagus, at times present during tox- emia, i. 606 greater than sympathetic, i. 192 in digestive tube, i. 258 predominates, i. 193 Toxemia, absence of symptoms of, does not indicate healing, case illustrating, ii. 607 action of, upon heart, i. 231 acute, injures nerve cells, i. 221 and anaphylaxis, contrasted, ii. 158, 341 and brain cells, i. 160 and nervous system, i. 151 and neurasthenia, i. 158 and temperature curve, ii. 142 causes sweating, ii. 450 characteristics of symptoms due to, i. 366, 368 decreases appetite and digestion, ii. 285 due to intestinal stasis, i. 268 early symptoms of pulmonary tu- berculosis due to, i. 366 effect on heart, i. 245 case illustrating, ii. 618 fever an index to, ii. 129 fever part of syndrome of, ii. 108, 452 importance of symptoms due to, i. 605 increased by exercise, ii. 284 intermittent, temperature curve of, ii. 133 periods of, not necessarily serious, ii. 575 reduces nutrition, ii. 327 relationship to internal secretions, i. 366 relieves asthma, ii. 161, 167 Toxemia — Cont 'd severe, produces vasomotor paral- ysis, ii. 345 temperature curve of, ii. 138 symptoms due to, in advanced tu- berculosis, i. 437 symptoms of, ii. 110, 159, 527 case illustrating, ii. 537, 549, 590, 600, 609, 613 marked, case illustrating, ii. 546 syndrome of, i. 221; ii. 159 and general tuberculin reaction, i. 511 ; ii. 342 prolonged by wrong living, i. 367 Toxic reaction, not an immunity reac- tion, ii. 341 Toxins, act centrally, i. 223 affect nervous system, i. 108 and blood pressure, i. 236 constant action of, disturbs nerve quilibrium, ii. 390 continually bombard brain in active tuberculosis, ii. 393 injure nerve cells, ii. 392 may produce hemorrhage, ii. 174 Trapezius muscle, change in contour of, of diagnostic importance, i. 407, 467 in diagnosis of pulmonary tuber- culosis, i. 401 innervation of, i. 296, 328, 331 Trauma, relationship of, to tubercu- losis, i. 313 Traumatic tuberculosis, i. 312 Treatment, active, in tuberculosis, ii. 193 arsenic in, ii. 465 artificial pneumothorax in, ii. 429 atropin in, ii. 469 bromides in, ii. 468 case illustrating result of, ii. 532 character of, and prognosis, i. 644 characteristics of, valuable meas- ures in, ii. 203 codliver oil in, ii. 467 cold sponge in, ii. 407 cooperation in, depends on intelli- gence, ii. 220 cost of sanatorium, ii. 488 creosote in, ii. 463 definiteness essential to success in, ii. 204 earliness of, and prognosis, i. 642 effect of light in, ii. 421 entertainment not a necessity in, ii. 300 INDEX 697 Treatment — Cont 'd haphazard, proves disastrous, case illustrating, ii. 636 heliotherapy in, ii. 414 technic, ii. 423 home, ii. 470 and prognosis, i. 645 hydrotherapy in, ii. 401 hypophosphates in, ii. 467 importance of prolonged, case illus- trating, ii. 563 improved natural resistance, import- ant principle in, ii. 200 intelligent guidance most important factor in, ii. 254 intelligent, requires knowledge of pathological condition, ii. 287 intensive, ii. 500 interruption of, ii. 383 iodine in, ii. 465 iron in, ii. 468 length of sanatorium, ii. 498 length of tuberculin, ii. 382 length of, with artificial pneumo- thorax, ii. 437 method of, more important than measure, ii. 206 most valuable measures in, act in- directly, ii. 202, 209 of atonic constipation, i. 271 of cough, ii. 447 wet jacket in, ii. 411 of failing heart, i. 249 of fever by air baths, ii. 455 of hemorrhage, ii. 175 case illustrating, ii. 617 of insomnia, ii. 459 of intestinal stasis, i. 268 of night sweats, ii. 451 of pain, ii. 457 in tuberculous enteritis, case il- lustrating, ii. 648 of pneumothorax, ii. 87 case illustrating, ii. 630 of spastic constipation, i. 275 of symptoms of tuberculosis, ii. 445 of tuberculosis, cold air in, ii. 272 depends on close detail, ii. 222 importance of psychotherapy in, ii. 206 proper mental attitude in, ii. 205 rational basis of, ii. 188 rest and exercise in, ii. 282 of tuberculosis of bladder, ii. 101 of tuberculosis of kidney, ii. 100 of tuberculous laryngitis, ii. 28 Treatment of tuberculous laryngitis — Cont'd case illustrating, ii. 630 compresses in, ii. 31 medicinal measure in, ii. 29 rest to larynx in, ii. 31 of tuberculous meningitis, ii. 91 open air, technic of, ii. 248 pathological changes must be borne in mind during, case illus- trating, ii. 640 pharmacological remedies in, ii. 461 program for, case illustrating, ii. 592 remedies with general action in, ii. 463 requirement of measures in, ii. 201 results of artificial pneumothorax in, ii. 443 results of sanatorium, ii. 493 sanatorium, ii. 481 and prognosis, i. 645 spray bath in, ii. 409 success of, depends on close medical guidance, ii. 223 technic of artificial pneumothorax in, ii. 434 technic of using psychotherapy in, ii. 396, 398 tepid sponge in, ii. 410 tuberculin, choice of patients for, ii. 351 effects of, ii. 384 indications and contraindications for, ii. 352 when withhold, ii. 362 value of remedies employed in, rel- ative, ii. 206 value of tuberculin in, ii. 202 Trional in insomnia, ii. 459 Trudeau, and artificial immunization, ii. 335 Trudeau school for tuberculosis, ii. 379 Tubercle, caseation and rupture of, case illustrating, ii. 573 conglomerate, i. 27 conversion into fibrous tissue, i. 26 formation of, i. 25 growth of, i. 26 necrosis and caseation of, fol- lowed by hemorrhage, case illustrating, ii. 614 necrosis of, i. 26 protein an antigen, ii. 336 698 INDEX Tubercle— Cont'd softening and expulsion of, follow- ed by relief of symptoms, case illustrating, ii. 613 symptoms following caseation of, case illustrating, ii. 559 Tubercle bacilli, bunches of, in urine, i. 574 careful technic necessary for com- parison of, i. 565 disappearance of, from sputum, i. 582 frequency of, in feces, i. 579 in feces, does not mean bowel in- fection, i. 579 in feces, when no sputum raised, i. 580 in urine, method of examining for, i. 574 length of index for, i. 567 lengths of, method of determining, i. 565 method of examining for, in feces, i. 579 Tubercle bacillus vaccine (T. B. V.) Spengler, ii. 355 Tuberculin, ii. 329 administration of, controlled by careful physical examination, ii. 379 administration of, presupposes a knowledge of the clinical course of tuberculosis, ii. 380 aids in absorption of pleural ef- fusion, ii. 59 an immunity reaction, ii. 341 and physical examination, ii. 382 and prognosis, i. 652 animal experiments with, inconclu- sive, ii. 333 apparatus for making dilutions, ii. 357 Beraneck, ii. 355 bovine, ii. 356 case illustrating employment of, ii. 532, 539 in advanced tuberculosis, ii. 576 choice of patients for treatment with, ii. 351 choice of preparation, ii. 357 clinical hypersensitiveness to, ii. 347 constantly set free from focus of infection, ii. 330 Tuberculin — Cont 'd contraindication for use of, ii. 352 difference in action toward human beings and animals, ii. 334 different skins react differently to, i. 601 difficult to treat active tuberculo- sis with, ii. 349 dilution for subcutaneous test, i. 507 dosage in different types of the disease, ii. 366 dosage of, in subcutaneous test, i. 508 must be considered with interval, ii. 370 efficacy of, shown in tuberculous laryngitis, ii. 384 shown in tuberculosis of tongue, ii. 385 failure of patient's own to cure, ii. 347 fibrosis in pulmonary tuberculosis, hastened by its use, ii. 385 focal reaction to, ii. 340 from different strains of bacilli dif- fer, i. 601 general reaction causes syndrome of toxemia, ii. 342 general reaction in, ii. 337 general reaction to, due to toxic molecule, ii. 337 haphazard administration of, not best, ii. 365 hypersensitiveness, and character of lesion, i. 505 appears with focus, i. 506 diminishes with healing, i. 506 varies with virulence, i. 506 hypersensitive reaction to, specific, i. 513 importance of, graphic chart of pa- tient during treatment with, ii. 381 knowledge of pathological changes when administering, ii. 379 observing focal stimulation in, ii. 364 in circumscribed, moderately active tuberculosis, ii. 367 in diagnosis of tuberculous laryngi- tis, ii. 28 indications for use of, ii. 352 individualization in doses of, ii. 366 in early clinical tuberculosis, ii. 366 INDEX 699 Tuberculin — Cont 'd in moderately active, widespread tu- berculosis, ii. 368 in moderately advanced slightly ac- tive tuberculosis, ii. 367 interval between doses varies with size of dosage, ii. 376 intravenous administration of, ii. 363 in treatment of, tuberculosis of bladder, ii. 101 tuberculous kidney, ii. 100 tuberculous ovary, ii. 103 in widespread active tuberculosis, ii. 369 in widespread moderately active tu- berculosis, ii. 368 its safety for general use, ii. 378 Koch's Old, contains greatest num- ber of partialantigens, i. 506 local reaction to, ii. 338 method of administering, ii. 363 method of designating dosage of, ii. 361 method of diluting, ii. 357 method of dosage of, ii. 365 must be supported by other meas- ures, ii. 384 necessary for cure of tuberculosis, ii. 330 not a perfect remedy, ii. 202 oral administration of, ii. 363 phenomena following injection of, ii. 371 poisonous nature of, ii. 329 preparations commonly used, ii. 353 produces immunity, ii. 330 R. Koch, ii. 355 relationship of dosage to tempera- ture elevation, case illustrat- ing; ii. 642 schematic illustration of action of, ii. 346 phenomena following injection of, ii. 375 phenomena following repeated small dose and production of toximmunity, ii. 377 scheme for administration, ii. 372 scheme for diluting, ii. 359 sensitization to, a peripheral nerve stimulation, ii. 342 site of injection, ii. 364 small dose of, ii. 371 stimulates fibrosis, ii. 332 Tuberculin — Cont 'd stimulates more recent tubercles to healing, ii. 349 stop, during hemorrhage, ii. 182 time of day for injection of, ii. 365 use of, best learned by observing those who give it well, ii. 379 use of, in acute caseous, case illus- trating, ii. 627 value of, in treatment, ii. 202 variability of, i. 601 what is designated by, ii. 329 when dose should be given, ii. 372 when withhold during treatment, ii. 352 why administration of, aids cure, ii. 348 withheld during complications, ii. 352 withheld during hemorrhage, ii. 352 Tuberculin reaction, ii. 236 and anaphylaxis, ii. 162 and prognosis, i. 635 antigen-antibody reaction, i. 503, 513 depends on reactive ability of body cells, i. 503 focal, i. 510 why not present in necrotic areas, ii. 348 general, i. 510 diagnostic value of, i. 511 symptoms of, i. 510 syndrome of toxemia, i. 511 in larynx, ii. 18 local, i. 509 meaning of prompt marked, i. 504 most marked during activity, i. 600 prompt, means active lesion, i. 505, 513 temperature curve characteristic of, i. 511 Tuberculin test, concealed tuberculo- sis and, i. 504 conjunctival, i. 502 positive reaction, i. 515 cutaneous, i. 512 increases our knowledge of tuber- culous infection, i. 502 meaning of prompt reaction to, i. 504, 513, 600 positive reaction, i. 514 real value of, i. 513 rules for making, i. 513 700 INDEX Tuberculin test, cutaneous — Cont'd strength of tuberculin used in, i. 514 dilution of tuberculin for making, i. 507 focal reaction in, i. 510 general reaction, i. 510 importance in diagnosis, i. 599 in moderately advanced active tu- berculosis, ii. 536 intradermal, i. 515 Koch's Old tuberculin used for, i. 506, 514 percutaneous, i. 515 real value, generally underestimated, i. 504 reveals frequency of infection in childhood, i. 100, 102 should be made carefully, i. 514 subcutaneous, i. 506 cases applicable in, i. 508 dosage in, i. 508 positive reaction to, i. 509 temperature in, i. 507 Tuberculin treatment, case illustrat- ing, ii. 559 effects of, ii. 384 length of, ii. 382 Tuberculins, of different manufactur- ers compared, i. 602 Tuberculosis, ability of medical men to cope with, improving, ii. 209 acidosis in, i. 456 active, and prompt maximum tuber- culin reaction, i. 513 can x-ray determine, i. 518 clinical evidence of, case illus- trating, ii. 604 difficult to treat with tuberculin, ii. 349 shows most marked tuberculin re- action, i. 600 shows waves in temperature curve, .case illustrating, ii 614 treatment in, ii. 193 without syndrome of toxemia, i. 368 activity in, means multiplication of bacilli, ii. 190 acute, in early childhood, i. 98 in small animals, ii. 335 Tuberculosis — Cont 'd acute caseous, case illustrating, ii. 621 in prognosis, i. 630 acute miliary temperature of, ii. 128 advanced, acromion process in, i. 471 anorexia in, i. 439 appetite, loss of, in, i. 439 auscultation in, i. 478 blood changes in, i. 437, 585 bronchitis in, i. 460 cavity in, i. 489 changes in respiratory rhythm in, i. 478 chests, shape of, in, i. 471 circulatory disturbances in, i. 442 colds in, i. 460 compensatory emphysema in, i. 493 contour of chest wall in, i. 468 cough in, i. 450 difficult to heal, ii. 201 digestive disturbances in, i. 439 dry pleurisy in, i. 496 dyspnea in, i. 457 endurance, lack of in, i. 438 extension from primary metasta- ses, i. 435 extrapulmonary rales in, i. 482 fever in, i. 445 fibrosis in, i. 488 harsh breathing in, i. 479 heart in, i. 442 hectic flush in, i. 458 hemoptysis in, i. 460 hoarseness in, i. 447 importance of careful diagnosis in, i. 435 inspection in, i. 464 case illustrating, i. 469 larynx, tickling in, i. 450 malaise in, i. 438 menstrual irregularities in, i. 460 metabolic changes in, i. 440 movement of chest wall in, i. 468, 475 muscle degeneration in, i. 466, , 473 muscle spasm in, i. 466, 473 nausea in, i. 440 nervous system, changes in, i. 150, 168, 217 night sweats in, i. 445 INDEX 701 Tuberculosis, advanced — Cont 'd pains in chest and shoulders, in, i. 452 palpation in, i. 472 percussion in, i. 477 phthisical chest in, i. 465 physical examination in, i. 464 pleural effusion in, i. 496 pleurisy in, i. 460 prolonged expiration in, i. 478 pulmonary infiltration in, i. 482 quality of respiratory note in, i. 479 rales in, i. 480 rough breathing in, i. 479 scapulae in, i. 471 shoulders, drooping of, in, i. 471 skin, atrophy of in, i. 466 sputum in, i. 458 strength, loss of, in, i. 438 subcutaneous tissue, atrophy of, in, i. 466, 473 thickened pleura in, i. 497 toxic symptoms in, i. 437 trapezius, outline of, in. i. 467 vomiting in, i. 440 weight, loss of, in, i. 440 advanced cases, rarely loose bacilli, i. 584 advanced pulmonary, course of, un- even, i. 435 etiological classification of symp- toms in, i. 436 signs and symptoms of, i. 435 affects all systems of body, ii. 219 air, food and hygiene, not cures for, ii. 203 all body cells sensitized in, ii. 337 altitude treatment of, initiated by Archibald Smith, i. 647 and appetite, i. 255 and asthma, ii. 164 and chronic purulent bronchitis, differentiation of, i. 614 and climate, ii. 254 and constipation, i. 269 and definite air-borne diseases com- pared, i. 67 and double personality, i. 150 and food, ii. 308 and general asthenia, i. 612 and hypochlorhydria, i. 259 and influenza, differentiation of, i. 614 and insanity, i. 150 Tuberculosis — Cont 'd and intercostal neuralgia, differen- tiation of, i. 613 and marriage, ii. 516 and mental attitude, i. 153 and neurasthenia, i. 158 and open air, ii. 227 and organic heart lesions, i. 243 and overfeeding, ii. 310 and sea air, ii. 265 and underfeeding, ii. 314 application of light in treatment of, ii. 421 Arneth's classification of neutro- philes in, i. 577 artificial pneumothorax in treat- ment of, ii. 429 automobiling in, ii. 300 belongs to general medicine, ii. 208 blood pressure in, i. 235, 303 blood spitting, an early sign of, ii. 169 makes diagnosis of, almost cer- tain, ii. 170 brachial neuritis in, i. 161 caseous, characteristics of, i. 41 cause of apathy toward, ii. 187, 208 cause of fever in, ii. 286 changes in neutrophile in, i. 577 characteristics of valuable measures in treatment of, ii. 203 chronic fibro-ulcerative, temperature curve of, ii. 129 chronic, periods of activity in, case illustrating, ii. 548 chronic ulcerative, and prognosis, i. 629 cleansing bath in, ii. 412 clinical, early, anemia in, i. 364 blood spitting in, i. 364 bronchitis in, i. 364 intercostal neuralgia in, i. 364 la grippe in, i. 364 malaria in, i. 364 neurasthenia in, i. 364 slow recovery from disease in, i. 365 evidences of healing in, ii. 193 in adult, a metastatic disease, i. 360 present illness, importance of careful inquiry into, in diag- nosis, i. 365 present without fever, i. 373 close medical guidance is essential in, ii. 223 702 INDEX Tuberculosis — Cont 'd clothing in, ii. 250 Coccidioidal granuloma, differenti- ated from, i. 621 cold air in, ii. 271 cold bath in, ii. 407 cold feet in, ii. 251 colds as early symptom of, case il- lustrating, ii. 537 colds in, i. 607 compensatory changes in, i. 281 compensatory emphysema in, i. 284 concealed, difficult to detect, i. 504 curability of, depends on physician, ii. 212 judged by best results, ii. 188 cured in all climates, ii. 261 cure of, why aided by tuberculin, ii. 348 definite technic in treatment of, ii. 205 definiteness in therapy necessary to success, ii. 204 determining indican in, i. 572 diagnostic and prognostic values of blood findings in, i.. 585 urinary findings in, i. 585 diazo reaction in, i. 569 difference in symptomatology of early and advanced, i. 435 differentiated from, actinomycosis, i. 620 aspergillosis, i. 621 blastomycosis, i. 621 bronchiectasis, i. 614 bronchitis, i. 613 pneumonia, i. 617 pulmonary infarct, i. 616 pulmonary syphilis, i. 618 streptothricosis, i. 621 differs at different age periods, i. 96 dilatation of stomach in, i. 262 displacement of heart in, i. 283, 285 diurnal variation in temperature curve in, ii. 125 duty of state and municipality in preventing, ii. 514 early, bronchitis in, i. 390 cause of fever in, ii. 126 character of respiratory sounds in, i. 610 chest and shoulder pains in, i. 388 circulatory disturbances in, i. 387 Tuberculosis, early — Cont 'd cough in, i. 386 diagnostic importance of condi- tion of muscles and sub- cutaneous tissues in, i. 398, 405 digestive disturbances in, i. 370, 388 feeling of being run down in, i. 369 flushing of face in, i. 389 heals readily, ii. 200 hoarseness in, i. 385 increased pulse rate in, i. 381 lack of endurance in, i. 369 loss of strength in, i. 369 loss of weight in, i. 370, 388 malaise in, i. 369 nervous instability in, i. 369 night sweats in, i. 371 percussion changes in, i. 420 pleurisy in, i. 391 reflex symptoms in, i. 384 respiratory sounds in, i. 429 rise in temperature in, i. 371 spitting blood in, i. 390 sputum, i. 392 symptoms of, i. 357 temperature curve of, ii. 126 temperature of, that of continu- ous toxemia, ii. 126 urochromogen reaction in, i. 570 x-ray in diagnosis of, i. 611 early afebrile, rest and exercise in, ii. 284 early clinical, a metastatic infec- tion, ii. 189 in adult, ii. 506 early course of, case illustrating- ii. 625 early lymphatic, importance of, i. 110 early pulmonary, auscultation in, i. 426 clinical symptoms of, i. 357 harsh breathing in, i. 433 impeded breathing in, i. 431 physical examination of, i. 394 preceded by pleurisy, ii. 49 rough breathing in, i. 430 weakened breathing in, i. 430 whispered voice in, i. 434 why respiratory sounds differ, i. 142 effect of, displacement of heart in, i. 292 INDEX 703 Tuberculosis, effect of — Cont'd ozone on, ii. 263 sea air on, ii. 265 upon nervous system, ii. 392 upon heart, i. 236 enterocolitis in, i. 264 exacerbation of symptoms in, case illustrating, ii. 625 examination of, blood in, i. 575 feces in, i. 578 sputum in, i. 534 urine in, i. 568 exertion, greatest cause of death in, ii. 298 extensive with little necrosis, case illustrating, i. 606 fact of being considered fatal, hin- ders diagnosis, i. 597 factors affecting temperature curves in, ii. 124 factors reducing efficiency of circu- lation in, ii. 289 failing heart in, i. 248 failure of patient's own tubercu- lin to cure, ii. 347 family history in, i. 361 fever in, ii. 108 irregular, ii. 129 fibrocaseous, characteristics of, i. 41 fibroid, characteristics of, i. 40 takes on necrosis, i. 41 follows crowded condition, ii. 270 general profession fails to appreci- ate necessity of active treat- ment in, ii. 194 glandular, diagnosis of, i. 114 graduated exercise in, ii. 301 healing of, and temperature curve, ii. 142 heliotherapy in treatment of, ii. 414 hemorrhage and, i. 607. ii. 168 hemorrhage as early symptom of, ii. 542 hidden focus of, dangerous, i. 599 hidden, importance of, i. 596 high grade of immunity developed in, ii. 330 home treatment of, ii. 470 hopeful attitude of, ii. 155 horseback riding in, ii. 299 how to inform patient of its pres- ence, ii. 214 hydrotherapy in, ii. 401 Tuberculosis — Cont 'd ill effects of use of hot water bot- tles in, ii. 250 immunity in, relative, ii. 195 importance of, proper mental atti- tude in treatment of, ii. 205 psychotherapy in treatment of, ii. 206 reflex symptoms in, i. 606 symptoms due to tuberculosis process per se, i. 606 telling patient of, ii. 213 important principles of healing in, ii. 192 improved natural resistance, import- ant therapeutic principle in, ii. 200 improves slowly, ii. 218 inactive temperature curve of, ii. 139 incubation period in, i. 65 indigenous, rare in arid regions, ii. 269 infection, in child, ii. 505 influenced by pregnancy, ii. 553 influence of, care and worry on, case illustrating, ii. 638 season on treatment of, ii. 273 in malaria, i. 612 in neurasthenia, i. 612 insomnia in, ii. 458 intensive treatment of, ii. 500 interest in, awakens slowly, ii. 186 intermittent toxemia in, ii. 133 its diagnosis and differential diag- nosis, i. 596 laryngeal, throat compress in, ii. 411 loss of motor power in, ii. 393 many exacerbations in chronic, ii. 218 meningitis in, ii. 88 mental power, disturbed in, ii. 393 method of using x-ray in, i. 524 miliary, and leucopenia, i. 591 miliary, cause of, i. 40 miliary, following hemorrhage, ii. 148 mixed infection, not common in, ii. 122 morbidity and mortality in, favored by lowered resistance, ii. 200 mortality of, greatest from 15 to 35 years, ii. 200 must be understood by general pro- fession, ii. 187 704 INDEX Tuberculosis — Cont 'd must have the aid of general medi- cine, ii. 208 nature of, ii. 195 should be explained to patient, ii. 220 no single cure for, ii. 254 not a danger in general hospital, ii. 518 not prevented by deep breathing, ii. 305 nutrition in, i. 252 of bladder, ii. 101 of bones, ii. 106 of colon, resection in, case illus- trating, ii. 654 of ear, ii. 106 of genitourinary system, ii. 96 of glands, pathology of, i. 54 of intestines, ii. 33 in prognosis, i. 632 of joints, ii. 106 of larynx, ii. 17 in prognosis, i. 631 of liver, pathology of, i. 53 of nose, pathology of, i. 46 of ovary, ii. 103 of pharynx, ii. 105 pathology of, i. 46 of pleura, ii. 49 of prostate, ii. 103 of seminal vesicles, ii. 103 of spleen, pathology of, i. 54 of testicle, ii. 102 of tongue, ii. 104 of tonsils, ii. 105 pathological changes in, i. 46 of tubes, ii. 103 open, in adult, danger of, ii. 509 open air, a great advance in treat- ment of, ii. 228 not a cure for, ii. 227 pain due to neuritis in, ii. 456 patient should know probable course of, ii. 397 peripheral nerves in, i. 160 pharmacopeial remedies in, ii. 461 physical examination and diagnosis of, i. 608 pleurisy in, i. 607 pneumothorax in, ii. 73 pneumothorax, recurrent in, ii. 85 pregnancy in, ii. 623 prevailing attitude of medical pro- fession towards, ii. 208 primarily a lymphatic disease, i. 32, Tuberculosis — Cont 'd primarily a lymphatic disease, i. 52, 55, 84, 112 primarily an infection of childhood, i. 95 principles underlying therapeutics of, ii. 186 prophylaxis in, ii. 503 psychotherapy in, ii. 392 wide application of, ii. 394 in treatment of, ii. 387 pulmonary, activity increased by prolonged strain, case illus- trating, ii. 644 blood borne, i. 33 diagnostic value of changed con- tour in trapezius muscle in, i. 407 lymph glands do not often become enlarged in chronic, i. 84 not diagnosed when bacilli first enter tissue, i. 602 relation of to fistula in and, cases illustrating, ii. 653, 656 x-ray in diagnosis of, i. 516 rational therapy of, ii. 188 relation of, body cells to nutrition in, ii. 327 trauma to, i. 313 requirement of therapeutic measures in, ii. 201 rest and exercise in, ii. 277 in treatment of, ii. 282 rest important in every case of, ii. 285 "roughing it" in, ii. 299 sanatorium treatment in, ii. 481 severe toxemia in, ii. 138 shifting of trachea in, i. 289 similarity to syphilis in stages, i. 357 skin should be kept active in, ii. 403 small lesions of, most curable, ii. 190 spontaneous healing of, ii. 191, 193 spray bath in, ii. 409 produce little harm, ii. 191 specialists in, favor active treat- ment, ii. 193 spread of, favored by lessened re- sistance, ii. 199 sputum in early diagnosis of, i. 601 statistics of different observers not comparable, ii. 386 stomach disturbances in, i. 257 suitable diet for, ii. 315 INDEX 705 Tuberculosis — Cont 'd suitable exercise in, ii. 298 swimming in, ii. 300, 410 suspected, physician's duty in, i. 396 symptoms of, during clinical activ- ity, ii. 218 heart strain in, ii. 290 technic of, applying exercise in, ii. 295 artificial pneumothorax in, ii. 434 using psychotherapy in treat- ment of, ii. 396, 398 tepid sponge in, ii. 410 therapeutics of inland climates m, ii. 268 traumatic, i. 312 treatment of, depends on close de- tail, ii. 222 treatment of neurasthenia in, ii. 398 treatment of symptoms of, ii. 445 tuberculin in, ii. 329 usually advanced before diagnosed, i. 60S valuable measures in treatment of, act indirectly, ii. 202 value of study of sputum in, i. 535 value of temperature in diagnosis of, i. 607 value of tuberculin in treatment of, ii. 202 vasomotor system unstable in, ii. 143 warm air in, ii. 271 wasting in, ii. 320 why difficult to cure, ii. 348 zones of pain in, ii. 456 Tuberculosis clinic, ii. 522 Tuberculous enteritis, effect in slow- ing pulse, case illustrating, ii. 654 muscle rigidity in, case illustrating, ii. 660 postmortem findings in, case illus- trating, ii. 656 temperature curve of, case illustrat- ing, ii. 654 Tuberculous infection, danger of, i. 504 Tuberculous meningitis, bromides in, ii. 91 case illustrating, ii. 94 ice cap in, ii. 91 symptoms of appear before recog- nized, ii. 94 Tuberculous patient, and suggestion, i. 156 Tuberculous patient — Cont 'd association with, in auult life of lit- tle danger, i. 363 does not differ from non-tubercul- ous in physique or form of body, i. 363 easily duped, i. 155 factors making open air valuable in treatment of, ii. 258 suspiciousness of, i. 151 temperature in, easily influenced, ii. 123 Tuberculous pericarditis, pathology of, i. 49 Tuberculous peritonitis, effect of operation on, i. 50 pathology of, i. 50 Tuberculous pleurisy, pathology of, i. 48 Tuberculous process, activity in, i. 26 per se early symptoms due to, i. 366 Types of individuals, classification of, i. 354 mixed, characteristics of, i. 351 Ulcer, tuberculous, i. 27 Underfeeding and tuberculosis, ii. 314 Urinary system, muscles of supplied by sympathetics, i. 176 Urine, bunching of bacilli in, i. 574 collection of specimens, i. 568 condition of, and prognosis, i. 639 diagnostic and prognostic value of, findings in, i. 585 diazo reaction in, i. 569, 585 examination of, i. 5f'8 indican determination in, i. 572, 586 in tuberculous kidney, ii. 98 technic of examining for tubercle bacilli, i. 575 tubercle bacilli in, i. 574 urochromogen in, i. 575, 585 value of 24 hr. specimen, i. 568 Urochromogen, and diazo reaction compared, i. 571 Urochromogen reaction, i. 570 and prognosis, i. 639 Urochromogen test, standardization of, i. 572 Urticaria, due to anaphylaxis, ii. 157 706 INDEX Vagotonia, inherited, illustrated in hay fever, ii. 162 marked, case illustrating, ii. 584 Vagotonic, asthma occurs in those naturally, ii. 166 Vagus, greater, action of may be se- lective, i. 174 and digestive tract, i. 254 characteristics of, action in, i. 227 peculiarities of, i. 170 peripherally irritated, causes re- flex symptoms, i. 604 structures supplied by, i. 175 system, i. 170 stimulated by pulmonary inflamma- tion, slows heart, i. 231 tonus, asthma indication of, ii. 164 indicated in slow pulse, ii. 551 in digestive tract, i. 440 , shown in puise, case illustrating, ii. 584, 618 Vaso dilatation, part of syndrome of toxemia, ii. 110 Vasomotor disturbance, marked, causes increased diurnal vari- ation in temperature, case il- lustrating, ii. 646 Vasomotor equilibrium, disturbance of, ii. 121 in severe toxemia, ii. 139 Vasomotor system, unstable in tuber- culosis, ii. 143 Vaughan, contributions to study of fever, ii. 113 discussion of protein fever, ii. 118 produces various types of fever arti- ficially, ii. 114 tuberculin reaction and anaphylaxis, ii. 341 Vegetables, carbohydrate value of, ii. 320 Vegetarianism, ii. 309 Vegetative nervous system, i. 169 and anaphylaxis, ii. 157 relation of symptoms to, i. 183 statement of terms used, i. 170, 186 Vegetative system, antagonistic ac- tion of greater vagus and sypathetic divisions of, i. 187, 198, 384 Vegetative system — Cont 'd cells of, travel out from the central nervous system, i. 170 connection with central nervous sys- tem, i. 170 Ventilation, poor, produces ill effects, ii. 246 Veratrum viride in treatment of hem- orrhage, ii. 178 Vincent, Swale, internal secretions, i. 169 Viscera, no single type of form, posi- tion or function for, i. 337 Visceral function, normal variation in, i. 333, 335 Visceral nerves, inhibitory action in, i. 174 Vocal fremitus in pneumothorax, ii. 80 Voice transmission over cavity, i. 492 Vomiting, in advanced tuberculosis, i. 440 in anaphylaxis, ii. 139 Von Behring and artificial immuniza- tion, ii. 335 Von Leyden, advantages of sanatori- um treatment, ii. 482 Von Muralt, discusses suspiciousness of tuberculous patient, i. 157 Von Pirquet, and tuberculin reaction, ii. 336 cutaneous tuberculin test, i. 502, 512 Von Ruck, and artificial immuniza- tion, ii. 335 water extract, ii. 355 W Walking, best exercise for tubercul- ous, ii. 299 Walsh, frequency of tuberculous in- fection of kidney, ii. 96 Walters, advantage of sanatorium treatment, ii. 482 Wassermann and Bruch, suggest ses- sile receptors in necrotic areas fully satisfied, ii. 348 Water, distilled, contaminated, pro- duces protein poisoning, ii. 179 Watery Extract, von Euck, ii. 355 Wax, interbacillary, solvents for, i. 548 Weather, psychological influence of, ii. 261 Webb, and artificial immunization, ii. 355 INDEX 707 Webb and Williams, experiments in active immunization, i. 96 Weber, discussion of climate, ii. 254 Weight, body, increases most in cool weather, ii. 273 effect of large increase in normal, ii. 312 gain of, goes with improvement, ii. 311 increases with improvement, ii. 531 loss of, as result of overdoing, ii. 532 due to depressive emotions, i. 441 in advanced tuberculosis, i. 440 compensatory, i. 441 part of syndrome of toxemia, ii. 110 satisfactory gain in, illustrated, ii. 562 seasonal changes in, ii. 293 Wet jacket in treatment of cough, ii. 411 Wet method of preparing sputum for examination, i. 556 Whispered voice in early pulmonary tuberculosis, i. 434 Williams, sign, i. 524 Wolff-Eisner, and tuberculin reaction, ii. 336 conjunctival tuberculin test, i. 502, 515 Woodhead, statistics of glandular tu- berculosis in children, i. 113 Woodruff, effect of light of tropics, ii. 426 Worry, effect on temperature curve, ii. 146 Wright, emphasizes small doses of tu- berculin, ii. 370 X-ray, accuracy and limitations of, i. 521 X-ray— Cont'd and physical examination, relative value of, i. 516 average, examination equals poor physical examination, i. 611 can it differentiate active and healed lesions, i. 518 cases illustrating reading of, plates, i. 527, 528, 529, 530, 532 fluoroscopic, method, i. 524 in diagnosis of pulmonary tubercu- losis, i. 516 in early diagnosis of tuberculosis, i. 611 in spontaneous pneumothorax, ii. 81 limited motion of diaphragm, shown by, i. 525 method of using, in pulmonary di- agnosis, i. 524 value of, in diagnosis, i. 517 X-ray plate, cause of normal hilus and trunk shadows in, i. 521, 524 interpretation of, i. 521 X-ray stereoscopic plate, and phys- ical examination compared, i. 526 cases illustrating, i. 527, 528, 529, 530, 532 value of, i. 524 Xylol and chloroform dissolve wax and distribute bacilli that are bunched, i. 549 Ziehl-Neilsen stain for bacilli, i. 556 Zinsser, tuberculin reaction and ana- phylaxis, ii. 341 Zunst, Loewy, Muller and Caspari, discussion of climate, ii. 255 COLUMBIA UNIVERSITY LIBRARY 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 rules of the Library or by special ar- rangement with the Librarian in charge. 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