METHODS IN MEDICINE METHODS IN MEDICINE THE MANUAL OF THE MEDICAL SERVICE OF GEORGE DOCK, M.D., Sc.D. FORMERLY PROFESSOR OF MEDICINE, WASHINGTON UNIVERSITY SCHOOL OF MEDICINE ; FORMERLY PHYSICIAN-IN-CHIEF ROBERT A. BARNES HOSPITAL, ST. LOUIS. / BY GEORGE R. HERRMANN, M.D., Pli.D., INSTRUCTOR IN MEDICINE, UNIVERSITY OF MICHIGAN ; FORMERLY HOUSE OFFICER, PETER BENT BRIGHAM HOSPITAL, BOSTON ; FORMERLY ASSISTANT IN MEDICINE, WASHINGTON UNIVERSITY ; FORMERLY RESIDENT PHYSICIAN ROBERT A. BARNES HOSPITAL, ST. LOUIS. ILLUSTRATED ST. LOUIS THE C. V. MOSBY COMPANY 1924 Copyright, 1924, By The C. V. Mosby Company {All rights reserved) Printed in U. S. A. Press of THE C. V. MOSBY COMPANY St. Louis TO ALDRED SCOTT WARTHIN PUPIL AND COLLEAGUE OF THE PHYSICIAN-IN-CHIEF TEACHER AND COUNSELLOR OF THE RESIDENT PHYSICIAN PREFACE An efficient system of organization is at least one important fac- tor in the successes of a great Medical Service, in private, as well as in institutional, practice. This manual represents a system which has proved successful in the Medical Service of Professor George Dock at the Robert Abbott Barnes Hospital, Saint Louis. It em- bodies many of the ideas of the Precedent Book of the Medical Service of Professor Henry A. Christian at the Peter Bent Brigham Hospital, Boston. Since the field is not covered, in this way, by any other single volume, the requests for the publication of this manual have been granted, with the hope that it may prove of service to others. The manual is intended to be a practical ward or bedside guide, an outline of sound minimal requirements in the complete, systematic diagnostic study; a system of essential emergency, scien- tific, therapeutic and dietetic management; and directions for the ever important and vital preservation of the valuable data in the record of each patient. The attempt has been made to arrange logically the material collected from diverse sources, and to con- dense it, at the same time retaining sufficient details for the prose- cution of the methods and the general interpretation of the results. The Manual is divided into five parts: Part I is made up of administrative methods, rules and detailed regulations to insure prompt, careful, complete and uniform han- dling of each case. These methods include a system of the duties of the resident staff from the resident physician down to the clinical clerks; notes and suggestions for history-taking, physical examina- tion and laboratory work, with the routine requirements for each type of case and the details of the ordinary clinical laboratory procedures. Part II consists of the special methods of clinical and laboratory investigation applied in a more complete study. Part HI outlines acceptable therapeutic methods with emergency measures and subsequent treatment and management. Part IV contains approved dietetic methods with practical diet lists. vii viii PREFACE Part V illustrates recording and graphic methods in the form of a composite history with representative charts of data from the usual types of cases. The sources of the material are indicated wherever possible. How- ever, in a compilation of this type, many deserving due credit will unavoidably be unrecognized. It is a pleasure to acknowledge my deep indebtedness to Doctor George Dock, who has fathered this effort from its very beginning to its completion, with encouraging advice and constructive criticism. Grateful recognition is also due Doctors Wm. H. Olmsted, Alan M. Chesney, and Frank N. Wilson for their generous aid in the parts dealing with metabolism, bac- teriology, and cardiology, respectively; Dr. R. Walter Mills and Dr. Sherwood Moore of the X-ray Department; Dr. Frank Ewerhardt of the Physiotherapeutic Department; Superintendent Louis H. Bur- lingham and Miss Elizabeth Green; and the assistant residents and internes, Doctors E. H. Terrill, L. P. Gay, A. B. Jones, H. Schuessler, E. W. A. Ochsner, R. W. Rudolph, F. A. Jostes, J. A. Evans, D. F. Kudner, A. D. Carr, M. T. Nelson, and S. H. Kahn, whose loyalty and cooperation have made the manual a success. To my brother, Louis G. Herrmann, I owe thanks for his help in many ways, but especially in the making of the charts. To Mrs. Dorothy Turner Corley I am deeply indebted for untir- ing clerical assistance. My wife, Anna Williams Herrmann, is deserving of my deepest gratitude for her constant assistance, deep interest, and stimulating encouragement in this effort, as in all of my work, from inception to realization. George Herrmann. Ann Arbor, Mich. CONTENTS PART I ADMINISTRATIVE METHODS DUTIES OF THE MEDICAL HOUSE STAFF CHAPTER I Resident Physician 1. General Duties 17 2. Medical or Ward Duties 17 3. Clerical Duties 18 4. Responsibilities and Miscellaneous Duties 19 CHAPTER II Assistant Resident Physicians Division of Duties into the Four Services 20 Duties in the Subdivisions 21 1. General, Metabolism of First Assistant Resident 21 2. Laboratory, Bacteriologic and Serologic Assistant Resident ... 21 3. Private Pavilion, Assistant Resident 22 Private Pavilion Duties 22 Heart Station Duties 23 4. Neurologic Assistant Resident 23 General Duties 24 Clerical Duties 24 Miscellaneous Duties 25 CHAPTER III Internes Division of Duties into the Five Services 26 Special Duties of the Private Pavilion Interne (Service 3) 26 Special Duties of the Neurology and Metabolism Interne (Service 4) . . 27 Special Duties of the Laboratory Interne (Service 5) 27 General Duties of Internes (Service 1 and Service 2) 28 Medical Teaching Rounds and Clinics 31 Consultation Requests and Other Requisitions 32 X-ray and Photographic Requisitions 33 Heart Station Clinical Pathology and Hydrotherapy Requisitions . . 34 General or Miscellaneous Rules, Notes and Suggestions 34 General Orders 34 Treatment and Drugs 35 Critical List 35 Transfer of Patients 36 1 2 CONTENTS Discharge of Patients 37 Autopsy Permits 38 Statements and Letters 39 Instruments and Laboratory Equipment 39 Miscellaneous The Manual 39 Important Hours 39 Answering Calls 39 The Central Medical Supply Room 40 CHAPTER IV Record Room Rules General Routine for Clinical Histories 42 Persons Entitled to See Histories 42 Rules for the Use of Records 42 Nurse's Routine 42 Interne's Routine 43 Visiting Staff Regulations 44 Borrowing Regulations 44 Emergencies, Night Access to Records 44 Emergencies, Sunday and Holiday Access to Records 44 Abstracts of Re-entry Cases, for Transfers of O. P. D. Cases ... 45 Transfers 45 Certificate of Release 46 Autopsy Permits 46 CHAPTER V X-Ray Department Rules General Requisitions 49 Hours 49 Pyelograms 49 Fluoroscopic Examinations of Chest 49 Photographs and Prints 50 X-ray Treatments 50 Emergencies . 50 Outside Cases 50 Preparation Fluoroscopic Examinations of Gastro-Intestinal Tract 50 Urinary Tract Plates 51 Gall Bladder Plates 51 X-ray Reports 51 Unsatisfactory Plates 51 Personal Examination 51 Removal of Plates from X-ray Room 51 Removal of Plates from the Hospital 51 Old Plates 52 CONTENTS 3 Prints of Plates 52 Dental Films 52 Report of X-ray Findings 52 X-rays on Students, Nurses and Employees 52 CHAPTER VI Superintendent's Rules Some Important Things for House Men to Remember 53 Coroner's Cases 54 Advisable Route for Showing Visitors about the Hospital 54 CHAPTER VII General Directions for Members of the Senior Student Group in Medicine General Directions 55 CHAPTER VIII History Taking and Physical Examination Notes and Suggestions " Outlines for Case-Taking" by Prof. George Dock 58 Front Page 58 History Proper, Admission Note, Complaint, Past History and Present Illness 59 Present Symptoms 60 Diagnoses from History 60 Physical Examination, General External Features 60 Regional Abnormalities 61 Abstracts from O. P. D. Histories 61 Notes and Diagnoses 61 Side Headings and Paragraphs 61 Diagnoses 62 Abbreviated Histories 63 Special Case Histories 64 Rules Concerning Abstracts for Department of Pathology 64 CHAPTER IX Laboratory Notes, Suggestions and Rui.es Miscellaneous Suggestions 65 General Rules 66 CHAPTER X Laboratory Routines and Methods 1. Routine Sputum Examinations 67 Routine Methods of Sputum Study 67 Concentration of Elastic Tissue 68 Concentration of Organisms 68 Ziehl-Neelsen Stain for Tubercle Bacilli 68 Gram's Stain for Differentiating Organisms 68 2. Routine Examinations of Stomach Contents 69 Routine Methods of Gastric Analysis 69 4 CONTENTS Qualitative Tests for ' ' Free Hydrochloric Acid " 69 Boas' Method 69 Gunzburg's Test 70 Quantitative Estimations of Acidity 70 Lactic Acid Tests 71 Tests for Bile and Blood 71 3. Routine Stool Examinations 71 Routine Methods of Study of Feces 72 Tests for Occult Blood 72 The Guaiac Test 72 The Benzidine Test 72 The Spectroscopic Examination 73 Tests for Hydrobilirubin and Bilirubin 73 The Saturated Mercury Bichloride Test (Schmidt's) .... 73 Microscopic Reactions Applied to Feces 73 Acetic Acid, Lugol's Solution 73 Sudan III, Dilute Carbol Fuchsin 74 4. Routine Urine Examinations 74 Routine as to Specimens 74 Routine as to Examination of Urine 75 Routine Methods of Urine Study 76 Qualitative Tests for Albumin 76 Nitric Acid Test (with rough estimation of amounts) .... 76 Heat and Acetic Acid Test 77 Acetic Acid and Potassium Ferrocyanide Test 77 Differentiation of Substances Giving Suggestively Positive Albumin Reactions 77 Hetero-Pnoteose or Bence-Jones' Body 77 Nucleo-albumin and Mucin 77 Quantitative Methods for Albumin Estimation 78 Esbach's Method 78 Kwilecki's Modification 78 Tsuchiya's Modification 78 Qualitative Tests for Glucose 79 Fehling's Test 79 Benedict's Test 79 Fermentation Test 79 Differentiation of Substances Giving Suggestively Positive Glucose Re- actions ... 79 Phenylhydrazine Crystals 80 Bial's Orcinol Test 80 Borchardt's Resorcinol Test 80 Quantitative Methods for Glucose Estimation 80 Benedict's Method 80 Other Qualitative Tests Applied to the Urine Routinely .... 81 Diacetic Acid Tests 81 Gerhardt's Modified Ferric Chloride Test 81 CONTENTS 5 Arnold's Modified Amidoacetophenon Test 81 Acetone Tests 81 Lange's Nitroprusside Test 81 Gunning's Iodoform Test 81 Tests for Urinary Pigments 82 Bile Tests, Foam and Nitric Acid 82 Urobilinogen Test (Ehrlich's Aldehyde) 82 Urobilin (Schlesinger's reagent) 82 Blood Pigment Tests (Guaiac and Benzidine) .... 83 5. Routine Blood and Body Fluid Examination 83 Routine as to Specimens 83 Routine as to Examination of Blood (Fresh and Stained) .... 84 Routine Methods of Blood Study 84 Technic for Counting Erythrocytes 84 Technic for Counting Leucocytes 86 Estimation of Hemoglobin (Tallqvist and Sahli) .... 87 Computing Color Index 88 Making of Blood Films 88 Fixing and Staining of Blood Films 88 Study of Preparations, Characteristics of cell types ... 89 The Study of the Spinal Fluid 90 Lumbar Puncture Technic 90 Methods of Examining Spinal Fluid 91 The Cell Count 92 The Determination of Excess Globulin 92 The Determination of Excess Glucose 93 The Determination of Excess Urea and Chlorides ... 93 Bacteriological Examination 93 The Study of Other Body Fluids 94 Thoracentesis Technic 94 Pericardial Paracentesis Technic 95 Abdominal Paracentesis Technic 95 The Examination of Body Fluids 96 Classification of Pathologic Fluids 96 Ward Routine for Laboratory Specimens 96 Specimens to be Preserved 98 CHAPTER XI Equipment for Ward Workers Plan of Conduct of Ward Laboratories 100 Apparatus to be Supplied to Each Student 101 Equipment in Each Ward Laboratory 101 Special Apparatus Available on the Wards, etc 101 For Blood Examination, Circulation and Respiration .... 102 For Urine Examination and Miscellaneous Studies 103 The Eye and Ear Examination 104 Regular Examination Tray (contents) 104 6 CONTENTS Neurological Examination Tray (contents)105 Vaginal and Rectal Examination Tray (contents)105 CHAPTER XII Procedures to be Undertaken in the More Common Types of Cases Routine Study of All Patients107 Routine Study of Pulmonary Cases107 Routine Study of Pneumonia Cases107 Routine Study of Gastrointestinal Cases108 Routine Study of Typhoid Fever Cases108 Routine Study of Diabetes Mellitus108 Routine Study of Endocrine Cases109 Routine Study of Cardiac, Nephritic and Hypertension Cases .... 109 Routine Study of Blood or Hemopoietic System Cases 109 PART II SPECIAL LABORATORY METHODS CHAPTER XIII Special Procedures to be Applied in Gastrointestinal Cases Gastric Function TestsIll Admission TubingIll The Retention TestIll The Gastric Fractional ExaminationIll The Test Meals112 Details of Procedures for Aspirating Gastric Contents .... 112 Rehfuss Method, Gorham Method113 The String Test114 Gastric Ferments115 The Examination of Duodenal Contents116 Method of Aspiration of Duodenal Contents116 Duodenal Fractional Examination117 Analysis of Duodenal Content117 Estimation of Pancreatic Enzymatic Function117 Qualitative Estimations for Trypsin, Steapsin .... 117 Amylopsin118 Quantitative Estimations (Einhorn's Tubes) .... 118 Agar-Hemoglobin, Agar Olive-Oil, Agar-Starch . . 119 Quantitative Estimation (McClure's Methods) .... 119 Estimation of Proteolytic Activity119 Estimation of Lipolytic Activity123 Estimation of Amylolytic Activity124 Gall Bladder and Biliary Tract Diagnostic Procedure (Meltzer-Lyon) . . 126 Duodenal Pigment Estimation (Schneider)131 Bilirubin Estimation132 Urobilinogen and Urobilin Estimation133 CONTENTS 7 The Phenoltetrachlorphthalein Test for Liver Function ....... 134 The Duodenal Appearance Time Method 135 The Colorimetric Plasma Retention Method 136 The Bile Content of Plasma in Types of Jaundice 138 Blankenhorn's Method of Study of Plasma . 138 Van den Bergh's Method of Study of Plasma 140 The Fibrinolysin Test in Blood Plasma 141 Intestinal Function Test 141 Schmidt-Strasburger Diets 142 Tests for Fat Indigestion 144 Tests for Occult Blood in the Stools 146 Vaughan's Benzidin Method 146 Wohlgemuth's Benzidin-Ortizin Method 146 Spectroscopic Methods 147 Concentration of Ova in Stool 148 Concentration of Entamoeba Cysts in Stools 149 Urobilinogen and Urobilin Methods (Wilbur and Addis) 149 Duodenal Contents or Bile 149 Stools 150 Urine 151 Technic for Finding Mercury in Excreta Method of Vogel and Lee 151 Method Willard and Elliott 154 Detection of Methyl Alcohol in Excreta (Robinson) 155 CHAPTER XIV Renal Function Tests Phenolsulphonephthalein Test 157 Twelve-Hourly Urinary Output Records 159 Two-Hourly Renal Test (with Mosenthal's Diets) 160 Sharlet and Lyle's Method of Interpretation 164 Concentration Diuresis Test (Olmsted-Day) 165 Blood Chemistry Methods used in Renal Studies (Sec Chapter XVII, p. 220) Method of Search for Hemosiderin in Cells of Urinary Sediment . . . 167 CHAPTER XV Hematologic Studies Standardization of Hemoglobinometers (Sahli) 168 Van Slyke's Method .... 169 Jacobson's Method 169 Terrill's Method 171 The Carbon Monoxide Method of Colorimetric Determination of Hemoglobin (Palmer's Method) 174 Blood Grouping 176 Estimation of the Coagulation Time of Blood (Minot and Lee) . . . 178 Bleeding Time Estimations (Duke) 179 Blood Platelet Counting (Ottenberg) 179 8 CONTENTS Summary of Criteria Obtained from These Tests 180 The Fragility Test for Erythrocytes 180 Vital Staining 182 Oxidase Staining (Graham's Technic) 184 Peroxidase Reaction (Goodpasture's Technic) 185 Method of Concentrating Malaria Plasmodia (Bass and Johns) .... 186 CHAPTER XVI Miscellaneous Methods and Tests For Cardiological Studies 189 Exercise Tolerance Tests 189 Directions for Applying Electrodes for taking Electrocardiograms . . 191 Standardization of Digitalis by the Cat Method 192 For Endocrinological Studies 195 The Blood Sugar Tolerance Test 195 The Pharmacologic Tests 196 Adrenalin, Pilocarpin, Atropin Tests 197 The Pharmacodynamic Reactions . 198 Adrenalin, Pilocarpin, Atropin Reactions 198 Details to Observe when Taking the Status of the Vegetative Nervous System 199 Symptoms of Increased Vagotonia and Sympathicotonia .... 200 The Thyroid Test 201 The Thyroxin Test 202 The Pituitrin Test 204 For Immunological Studies 205 The Tuberculin Test 205 The Schick Test 206 The Pneumotoxin Test 207 Protein Sensitization Tests 208 CHAPTER XVII Physiological Chemistry Methods Determination of Gas in Respired Air 209 Methods of Collection of Alveolar Air 209 Methods of Analysis of Alveolar Air (Marriott's) 210 Blood Plasma and Whole Blood Carbon Dioxide or Carbonates Determination (Van Slyke's Method) .' 212 Blood Oxygen Determination (Van Slyke's Method) 216 A System of Blood Analysis (Folin and Wu Methods) 220 Precipitation of Blood Protein 220 Determination of Blood Non-protein Nitrogen 221 Urea 223 Urease and Aeration Method 225 Autoclave Decomposition Method 225 Creatinine and Creatine 225 Uric Acid (Folin's Last Modification) 226 CONTENTS 9 Amino-Acid Nitrogen 231 Chlorides (Whitehorn's Method) 232 Sugar (Folin's Last Modification) 234 Sugar (Shaffer-Hartmann Method) 235 Sugar (Myers-Bailey Method) 238 Sugar (Lewis-Benedict Method) 239 Fatty Acids and Cholesterol (Bloor's Last Modification) . . . 241 Cholesterol (Myers-Wardell Method) 244 Acetone Bodies (Van Slyke-Fitz Methods) 246 Chlorides (McLean, Van Slyke, Austin Method) 251 Calcium (Clark's Method) 253 Normal Values in Blood Chemical Determinations 257 CHAPTER XVIII Routine Bacteriological and Serological Methods Collection of Material 258 Routine Work 258 Records 259 Supplies 259 Disposal of Material 260 Bacteriological Methods 260 Pneumococcus Typing 261 Tubercle Bacillus Culturing . 262 Throat Cultures 262 Stool Cultures 263 Colon-Typhoid Group Differentiation 264 Urine Cultures 265 Exudates and Transudate Cultures 265 Spinal Fluid Cultures 266 Blood Cultures 267 Best Media for Growth 267 Media for Preserving Stock Cultures 268 Method for Demonstrating Spirochetae Pallidae (Warthin and Starry) . 271 Complement-Fixation Test Technic 271 PART III DIETETIC METHODS CHAPTER XIX General Ward Diets Diets in Infectious Diseases High and Low Caloric Diets Liquid Diet 277 Soft Diet 278 Light Diet 279 10 CONTENTS Regular Diet 281 Moderately High Caloric Diet 281 Convalescent Tuberculosis Diet , 282 Typhoid Diet, 3500 Calories 283 Coleman-Shaffer Dietetic Management of Typhoid Fever 284 Directions for Nurses 284 Table of Approximate Values of High Caloric Foods 285 High Caloric Typhoid Diets, 1000 Calories per day 286 1500 Calories per day 287 2000 Calories per day 288 2500 Calories per day 289 3000 Calories per day 290 Recipes and Substitutes, 3900 Calories per day 291 Arthritis Diets (After Pemberton) 294 Reduction Diets-Low Caloric Diets 296 CHAPTER XX Diets in Gastrointestinal Diseases Lenhartz's Ulcer Diet 300 Modified Lenhartz's Diet 302 Sippy Ulcer Diet 304 Modified Sippy Diets 305 Mill's Ulcer Diets 308 Bland Diet and Nonlaxative Diet 311 Coarse Diet and Laxative Diets 312 Spastic Constipation Diet 313 Atonic Constipation Diet 314 Schmidt's Intestinal Diet 315 CHAPTER XXI Important Organic and Inorganic Chemical Constituents in Diets The Treatment of Gout 316 Foods with Low Purin Content, Foods with High Purin Content . . . 317 Cholesterin and Lipoids in Diets 319 Iron Content of Foodstuffs 320 Calcium Content of Foodstuffs 322 Dietetic Treatment of Edema 324 Karell Diet 325 Epstein Diet 325 CHAPTER XXII Principles Governing the Diet in Nephritis High Nephritic Diet 327 Medium Nephritic Diet 328 Low Nephritic Diet 329 Low Protein High Caloric Diet 330 A Practical Nephritic Diet for Out-Patients (O'Hare and Wickers) . . 332 CONTENTS 11 CHAPTER XXIII The Treatment of Diabetes Mellitus Observation Diets 335 Starvation Diets 336 Bran Bread 336 Thrice Cooked Vegetables 337 What Carbohydrate Tables to Use 337 Weights of Average Servings in Grams 337 Axioms for the Diabetic 339 Table of Chief Carbohydrate Foods 339 Table of Foods of 5% or less Carbohydrate Content 340 Table of Foods of 5% to 15% and 15% to 25% C. H 341 Table of Foods of 15% to 40% and 40% and above C. H 342 Table of Vegetable Equivalents 343 Table of Protein 15% or less, and 15% to 25% 344 Table of Protein 25% and above 345 Table of Fats 345 Test and Maintenance Diets-Method of Increasing Diets 346 High Fat Diets 350 The Use of Insulin 352 PART IV THERAPEUTIC METHODS CHAPTER XXIV General Rules 365 Promptly Acting Powerful Drug's 367 Narcotic Drugs 368 Treatment Sheet 368 Table English Metric Equivalents 369 CHAPTER XXV Emergency Measures Intravenous Therapeutic Solutions 370 Normal Physiological Saline, 0.85 per cent 370 Alkali or Sodium Bicarbonate, 4 per cent (See also p. 394) . . . 370 Glucose 50% Stock, 5% Emergency 371 Hypertonic Gum Acacia Glucose 371 Sodium Citrate (Anticoagulant) 371 Treatment of Poisonings General Emergency Measures 372 Carbon Monoxide Poisoning 373 Mercury Bichloride Poisoning 374 Phenol Poisoning 377 12 CONTENTS Wood Alcohol Poisoning 377 Acute Cocaine Poisoning 378 Strychnine Poisoning 379 Acute Morphine Poisoning 379 Acute Alcoholism 380 CHAPTER XXVI Emergency Measures in General Diseases Treatment of Acute Heart Failure 381 Treatment of Acute Pulmonary Edema 383 Treatment of Adams-Stokes Attacks 383 Routine Management of Heart Cases 384 Digitalis Administration in Massive Doses 385 Diuretic Observation for all Edematous Cases 386 Digitalization in Divided Doses 387 Quinidin Therapy 387 Further General Measures 388 Treatment for Acute Uremia 389 Routine Management of Renal Cases 390 Treatment for Cerebral Hemorrhage 391 General Management of Hypertension Cases 392 Treatment of Diabetic Acidosis and Coma 393 General Management of Diabetes Mellitus Cases 394 Treatment of Heat Stroke 394 Treatment of Shock 396 CHAPTER XXVII Management of Infectious Diseases Strict Isolation Management of Contagious Diseases 398 Regulations for Acute Respiratory Disease 399 General Measures in Acute Infectious Diseases 400 Pneumonia 401 Typhoid Fever 401 Notes on the Management of Other Types of Cases 404 Malaria 404 Catarrhal Jaundice by Duodenal Lavage 404 Peptic Ulcer (hemorrhage, perforation, or pyloric obstruction) . . 408 Constipation 408 Diarrhea 409 Intestinal Parasites 409 Treatment of Taeniasis 409 Treatment of Amebiasis 410 Treatment of Uncinariasis 411 Enemata of All Types, Prescriptions, Notes 411 Rectal Taps 413 Murphy Drip Method 414 Notes on the Treatment of Blood Diseases 415 CONTENTS 13 Anemia 415 Leukemia 416 CHAPTER XXVIII Hydrotherapy Actions and Indications for Various Physical Methods Electric Light Bath 417 Local Baking 417 Scotch Douche 418 Whirlpool Bath 418 Nauheim Baths 419 Massage and Exercise 419 Actinic Radiation 420 CHAPTER XXIX Dock's Twenty Drugs General Rules 421 Opium 422 Arsenic 422 lodids 423 Iron 423 Quinine 424 Digitalis 424 Strychnine 423 Salicylates 425 Atropin 426 Bromides 426 Chloral 426 Ammonium Chloride 427 Phenacetin 427 Calomel 428 Bismuth 428 Nitrites 429 Acids and Antacids 429 Ipecac 429 Anthelmintics 430 Opotherapy-Desensitization, Sera and Vaccines 430 PART V RECORDING GRAPHIC AND CHARTING METHODS COMPOSITE HISTORY WITH ALL STANDARD TYPICAL CHARTS CHAPTER XXX The History in Order 432 Front Page 435 History Sheet with Margin Stamps 436 Mills' Anatomic Outlines of Habitus Types 437-438 14 CONTENTS Outlines for Locating Regional Abnormalities 439-447 The Pink Sheet (for blood examination records) 448-449 The Green Sheet (for sputum, stomach, stool and pathology records) . 450-451 Cross Section Paper used in Charts452 Special Blood Charts Anemia453 Leukemia454 Blood Pressure Chart455 Apex-Radial Pulse Deficit Chart456 Vital Capacity, Fluid Intake and Output, Weight Chart457 Electrocardiographic Record Sheets 458-460 Cardiac Charts 461-463 Gastric Analysis Charts 464-466 Duodenal Analysis Chart467 Twelve-Hourly Urinary Chart468 Cardio-Renal Chart469 Two-Hourly Renal Test Chart470 Metabolism Charts 471-473 Diabetic Data474 Diabetic Chart476 Sugar Tolerance Test Charts 477-478 Adrenalin Test Chart479 Basal Metabolism Rate Chart480 Cerebrospinal Fluid Chart 481-483 Perimeter Charts484 Vestibular Test Chart< ... 485-486 X-ray Examination Report 487-490 Gastro-Intestinal Orthodiagram491 Dental Sheets 492-495 Temperature, Pulse and Respiration Chart496 Bedside Notes Sheets 497-498 Diet Lists (Nurse's Chart)499 Measurements of Urine (Nurse's Record)500 Defecation Chart (Nurse's Record)501 Narcotic Report (Nurse's Record)502 Death Report (Nurse's Record)503 Refer Blank Form504 X-ray Requisition Form505 Wassermann Request Form505 Prescription Blank Form506 Clinical Pathology Form506 Hydrotherapy Requisition Form507 Autopsy Permission Form508 Superintendent's Autopsy Order Form508 Transfer Notice Blank Form509 Certificate of Release510 Note to Referring Physician Form511 INTRODUCTION The following pages originated in some brief and simple sugges- tions for the House Staff early in my hospital service. The material gradually became more comprehensive, with the rapid enlargement of the scope and variety of work expected of the house staff of a properly equipped hospital. All the resident physicians of the Wash- ington University and Barnes Hospital, clinical departments of Wash- ington University, were asked in turn to revise the rules according to their own experience or on suggestions of my own. Preceding George Herrmann the residents were: James S. Brotherhood, Hugh McCulloch, Drew Luten, Joseph F. Bredeck, W. H. Olmsted, R. K. Andrews and T. C. Redfern. Several of these were very successful in improving the material, in making it more complete and at the same time more orderly and more concise. Dr. Herrmann, by reason of his natural gifts and his training in the Peter Bent Brigham Hos- pital was able to bring the Manual, as we began to call it, to a per- fection not reached before. He also added many topics, in fact prac- tically all after Section I, so that by 1920 the material was almost as complete as in the present form. It was often noticed with ap- proval by medical friends and visitors. Many asked for copies, others suggested printing. When the matter was presented to Dr. C. V. Mosby, he made a careful examination and agreed to undertake the publication. The object of the book is to assist members of house staffs in the most efficient and economical use of time and material in the various duties assigned to them. These duties include all the details of work with patients, their relatives, family physician or occasional consult- ants ; the preparation of histories, reports and letters, the making of all clinical and laboratory examinations indicated in each case for diagnosis, as guides to treatment, or for purposes of research. They include also the relation of the house staff to the rest of the hospital personnel, the health officers of the community and the use and care of laboratory equipment and supplies. All these things can, of course, be learned by practice, or may be handed down from one house staff to another, but with the increased 15 16 INTRODUCTION complexity of work it is easy for some members of a staff to lose time, to overlook important details, to miss essential information, or permit valuable specimens to disappear. Experience in the war period, when only a few of the older mem- bers of the staff were on hand, and relatively inexperienced men took their places, showed the great value of an easily accessible written guide. For such purposes the book may be used as we used the original copies. It is put in the hands of each new man as he comes on duty and he is asked to read it over carefully, to ask questions about all matters that seem obscure or uncertain, and to be guided in future by the spirit as well as the letter of the manual. It is not to be supposed that all details will be followed literally in all institu- tions. Even in my own service modifications were made from time to time, in the division of labor or in other ways, depending upon the personal qualifications of individuals. Nobody would regret it more than the author and the writer of these lines if the rules were supposed to be inflexible. The same is true of the various diagnostic or therapeutic methods. Many of these will probably long remain useful, but others, having been tried, will be discarded. If the general idea is followed it is believed that the house officer will use the book as a foundation for additions and modifications based upon his own reading and experi- ence, that from an early period his work will have a definite aim, with corresponding gains to his patients, to the rest of the staff, and to his own reputation. George Dqck Pasadena, Calif. METHODS IN MEDICINE PART I DUTIES OF THE MEDICAL HOUSE STAFF CHAPTER I RESIDENT PHYSICIAN 1. General Duties The resident physician is to be first assistant to the physician-in- chief at all times, and with him is to direct the work of the resident staff, to assign assistant residents and internes to their duties, and to arrange for the scheduled rotation of the men from private pavilion and heart station to metabolism and clinical laboratory and from ward to ward. To accompany the physician-in-chief on all his visits to the private pavilion as well as to the wards. To suggest the order of cases to be discussed in the teaching rounds. To arrange the material for the clinics of the physician-in-chief and assist in facilitating the execution of the program. To inform the physician-in-chief of the time set for surgical opera- tions or autopsies that are performed on patients that have been on the medical service. To notify the physician-in-chief immediately of any medical emer- gency on the private pavilion or any serious situation on the medical wards. To visit every emergency case at once; to see all seriously ill pa- tients daily, and each new case the day of admission, authorizing the immediate treatment and initial plan of management in each case. To make a daily general inspection of the whole medical service, accompanied by the internes on the wards, the assistant residents on 2. Medical or Ward Duties 17 18 METHODS IN MEDICINE the private pavilion and in the metabolism unit. To dictate history notes, suggestions and criticism, as seem indicated. To arrange the schedule for the daily teaching and nonteaching ward rounds, staff rounds and other visits. To conduct general ward rounds on Sundays and holidays and "teaching rounds" as assigned in the schedule of the regular medical work. To substitute at the request or in the absence of the physician- in-chief or any scheduled member of the visiting staff. To instruct internes as to when ward patients are to be discharged and to take care to see that patients, whether on the ward, in side rooms or on the private pavilion, sent to any member of the staff, are not discharged or transferred without first having notified the staff member concerned, obtaining his permission and recording same. To see cases returning for observation at stated times and add "follow-up" notes on important cases. 3. The Clerical Duties To receive all requests for consultation from other services and see that same are answered. To deliver (after signing) all similar re- quests from the medical service. To sign all slips authorizing the transfer of patients from the medi- cal service. To sign all x-ray requisitions, after noting that physical signs and provisional diagnoses are recorded on the requisition as well as in the history. To write, or see that a proper letter is written, to every patient's physician, whether the latter was directly responsible for the patient's presence on the medical service or not. All letters, except those of the physician-in-chief, are to be signed by the resident physician. Copies of all letters as well as the physicians' originals are to be filed with the history. To supervise the completion of the histories and diagnoses for presentation at the regular history meetings. For this reason he must receive all histories from the assistant residents the night before the history meeting. To hold the regular weekly history meeting at 12 o'clock, noon, each Tuesday. To confer with the record room on the correction and final completion of diagnoses and histories. RESIDENT PHYSICIAN 19 4. Responsibilities and Miscellaneous Duties The resident physician, in the absence of the physician-in-chief, assumes the chief responsibility and must therefore receive immediate notice of any emergencies, sudden changes in condition, or develop- ments in any case, the appearance of prognostic or diagnostic find- ings of grave or definite significance, mishaps or extraordinary happenings. Consultation with the coroner must be held by the resident physi- cian, on all cases in which there is a question of the case being medico- legal. Notification must be given the pathologic department in case a medico-legal autopsy is ordered by the coroner. Sick nurses are seen by the resident physician ONLY in emergen- cies or at night. After admission to the medical service sick nurses have the same status as any other medical patient. The daily sick call for nurses is to be held by the physician to nurses or his duly appointed substitute. The resident physician is to hold resident house staff meetings; to read and demonstrate to assistant residents and internes, at the begin- ning of the service and as frequently thereafter as is necessary, the rules and regulations, duties, methods and routine of the medical service. Also to emphasize the advantages of this Manual of the Medical Service as a handy reference book, and to call attention to any changes made in this book. To discuss questions of discharge of duties by the members of the resident staff, etc., outlining the work according to the principles of the service, with a constant view toward increased efficiency. The arrangements for the regular vacations, and for any absence of over eighteen hours from the hospital, are to be made by the resi- dent physician. The resident physician is to be on call at all times. Arrangements must be made for the first assistant resident or understudy to be on duty during the absence of the resident physician. CHAPTER II ASSISTANT RESIDENT PHYSICIANS 1. The routine work of the assistant residents will be divided into four services. Each assistant resident should have an opportunity to obtain all varieties of experience, and should be able to specialize in one of the subdivisions. The four services are as follows: (1) General; Metabolism. First Assistant Resident or Un- derstudy to Resident. In charge of Male Ward and Metabolism unit. (4 months' service-to rotate with 2 and 3). (2) Laboratory; Bacteriologic and Serologic. In charge of Female Ward and Colored Wards. Physician to hos- pital employees. (4 months' service-to rotate with 1 and 3). (3) Private; Heart Station. In charge of Private Pavilion medical cases. Admitting officer for Medical Service. (4 months' service-to rotate with 1 and 2). (4) Neurology. In charge of Neurologic patients through- out hospital. (12 months' service-no rotation). 1. METABOLISM AND MALE WARD 2. LABORATORY, FEMALE WARD AND COLORED WARD 3. PRIVATE PAVILION, AND HEART STATION 1. Asst. Resident 2. Asst. Resident 3. Asst. Resident July 1-Nov. 1 Mar. 1-July 1 Nov. 1-Mar. 1 Nov. 1-Mar. 1 July 1-Nov. 1 Mar. 1-July 1 Mar. 1-July 1 Nov. 1-Mar. 1 July 1-Nov. 1 4. Asst. Resident Neurology. July 1-July 1-12 months, non-rotating service. Rotation Schedule for Assistant Resident Services 2. The assistant resident is expected to pnt in one-half of the day, usually the morning, at his routine or assigned work, while the other half of the day, the afternoon, is to be spent in research work, or in the clinic perfecting his technic of special methods of examination as Ophthalmoscopy, Laryngoscopy, Bronchoscopy, Proctoscopy, Cyst- oscopy, etc., or doing general out-patient work. 20 ASSISTANT RESIDENT PHYSICIANS 21 Duties in the Subdivisions 1. General, Metabolism or First Assistant Resident, or understudy to the resident will have charge of Male Ward and metabolism unit and will do his special work in biochemistry. Will arrange for and make teaching rounds with the director of the metabolism laboratory. Will be responsible for the accurate standardization and weekly testing of all quantitative standard solutions in use on medical pa- tients. This applies especially to the standardization of colorimetric apparatus for the "phthalein" estimations, such as<the Hellige wedge and the Dunning ampules when they are in use. (See under Phthalein test. Special Procedures.) Also the standardization of the standard tubes for the Sahli hemoglobinometers. (See under Hemoglobin standardization: Special Procedures.) 2. Laboratory, Bacteriologic and Serologic Assistant Resident will have charge of the Female Ward and the Colored Wards and will do his special work in the biological laboratory. Will arrange for and make teaching rounds with the director of the biological laboratory. Will act as physician to hospital employees, examining and treat- ing sick employees of the hospital whenever called to see them. He can refer them to the 0. P. D. or send them in to one of the wards as he sees fit. Under the director of the biological laboratory the laboratory as- sistant resident is to have charge of routine culture work, Wasser- manns and vaccinations. Will do and verify blood groupings and will keep a list of donors in the various groups. For this purpose employees of the hospital and students in the various medical classes shall be grouped and their records kept in the laboratory. Will be in charge of, and responsible for, apparatus for determining fragility of the red blood cells. (Described under Fragility Test: Special Procedures.) Will be in charge of, and responsible for, apparatus for concen- trating malaria plasmodia. (Described under Malaria Concentrat- ing Method: Special Procedures.) Will be responsible for keeping in good condition the various stain- 22 METHODS IN MEDICINE ing mixtures, used in routine work in all medical laboratories, especially the Ziehl-Neelsen's, Gram's, Loeffler's and Wright's stains. 3. Private Pavilion, Assistant Resident will have charge of all private medical cases and will do his special work in the heart sta- tion. Will arrange and make general teaching rounds with the visiting consultant on cardiac and hypertensive cardiovascular-renal cases. Will meet him at a stated time daily when he has private patients in the side rooms or in the pavilion. Will act as admitting officer in charge of the admitting of all medi- cal patients, private as well as ward patients. In this he will confer with the superintendent and resident. When necessary he will direct internes to admit patients. Enough history should be obtained and a brieif but sufficient physical examination done, to be reasonably sure that the patient is not an emergency case for another service of the hospital. Where there is any question, members of other house staffs are to be called in consultation. In emergencies the resident is to be notified at once. Will notify the resident promptly of all admissions to the wards and side rooms as well as to the private pavilion. Private Pavilion Duties consist in general supervision of all medi- cal patients on the private pavilion and responsibility to the attend- ing physicians for the care of their patients. Will confer with the resident at stated times daily, and in any emergency, regarding pa- tients under his care. Will see that the interne has recorded promptly the routine history and physical examination, laboratory work and blood pressure, and shall himself make and record a physical examination on each patient admitted. Will make rounds with the attending physicians. In this he will be assisted by the interne and the members of the medical group as- signed to the pavilion. Will arrange for consultations as directed by the attending physi- cian. Will notify the superintendent's office promptly and accurately of the cause of death of any private pavilion patient. Will see that the medical instruments and supplies are kept in repair and in sufficient quantity on the pavilion. The duties of the pavilion should not require more than one and one-half hours of each morning. ASSISTANT RESIDENT PHYSICIANS 23 Heart Station Duties consist in taking the routine electrocardio- grams each morning and in carrying out exercise tolerance tests and making polygraphic tracings where such examinations are requested. Will record in the experimental index in the heart station all therapeutic quinidin or massive dose tincture of digitalis tests, diuretic tests, amyl nitrite tests and atropine tests. Will see all cardiac cases and see that the cardiac chart is filled out in each heart case and that data are recorded completely on the filing and mounting cards in the heart station. Will be responsible for instruments of precision used in cases of circulatory disease. All polygraphs must be in good condition and one must always be ready for use. Will be likewise in charge of all blood pressure apparatus on the medical service and must see that same is always in good repair. The duties outlined are those of the Fellow in Electrocardiography and in the absence of a holder of the fellowship, the duties fall on the private pavilion assistant resident. 4. Neurologic Assistant Resident will have direct supervision over all neurologic patients in the hospital, under the direction of the consulting neurologist. Will instruct the interne as to any neurologic or medical procedure that may be indicated and see that all routine measures are completed on all cases. Will be present to advise and share the responsibility in the per- formance of lumbar punctures in cases with increased intracranial pressure. Will make such special neurologic examinations as may be neces- sary and attach same to history. Will arrange for the consulting neurologist's teaching rounds and clinics, and see that all requests for neurologic consultations are filled, and that transfer from or to the neurologic service is promptly carried out. Will be in charge of and responsible for the upkeep of the neuro- logical examination tray and instruments, and also the ophthalmo- scope and perimeter. Will check all neurological diagnoses on histories and see that they are correct before each weekly history meeting. 24 METHODS IN MEDICINE General Duties Ward Duties.-Assistant residents are to visit their assigned wards and rooms at least twice each day for conference with the internes regarding the general condition of all patients. Each new case is to be questioned and examined by an assistant resident within thirty-six hours after admission. The findings are to be incorporated in the history under the margin title of "Sum- mary by Assistant Resident" and signed by the author. The sum- mary must be concise and correct, containing only verified essential points in the history and confirmed physical findings with the as- sistant resident's diagnoses. Not more than two-thirds of a page is to be used for the summary. Subsequent observations on the patients by the assistant residents are to be recorded in the history as signed and dated notes similar to those of the other staff members. Assistant residents are to suggest to the internes acceptable thera- peutic procedures, countersign all standing and special "stat orders." To recommend special examinations that seem indicated for diag- nosis or for purposes of investigation and to sanction proposed pro- cedures, as gall bladder diagnostics, proctoscopic examinations, lumbar punctures, paracenteses, et cetera, being present at these as he deems advisable. Clerical Duties.-Assistant residents are to see that all positive diagnoses, including those made by the specialists called in consulta- tions appear immediately on the front page of the history and that complete diagnoses have been made on all cases on transfer or dis- charge and that blackboard diagnoses have been made in all fatal cases. Furthermore, that all consultations, special procedures and special therapeutic measures have been noted under "REMARKS" on the front page of the history. The assistant residents are to inspect tbe students' or internes' histories for omissions or mis-statements, also as to the form and the English or grammar used, making notes toward their improvement in style as well as content. Also to see that the summary, the notes on special examinations and consultation notes are complete and cor- rect. In the case of discharged patients the assistant residents are to receive the histories from the internes on Sunday for a final critical ASSISTANT RESIDENT PHYSICIANS 25 review, which must be completed the night before the regular weekly history meeting. The assistant residents are to write letters to the physician of each patient after the patient has been in the hospital five days and the ordinary examinations have been completed and again on discharge, when a complete report is prepared and sent to the patient's regular physician. The notes to physicians should consist of a list of the diagnoses, a short summary of important history facts and all positive findings and an outline of the acceptable therapy and management with whatever results have been obtained. Miscellaneous Duties.-The assistant residents are to assist the in- ternes in obtaining consent for autopsies, arrange for the same with the superintendent and the pathologic department, and notify the resident and staff members who have seen the case of the time set for the autopsy. Autopsies are to be done as soon as possible after permission is obtained unless the physician-in-chief requests post- ponement. The assistant resident is to notify the superintendent's office and the resident promptly and accurately of the cause of death in each fatal case and where there is any question of its being a medico-legal case, such facts are to be stated. The assistant residents will fill out and sign all death certificates. The causes of death put on the death certificate must be entered in the history in a note. Assistant residents are to confer freely with the resident regarding any part of the routine work, especially any new developments or proposed new procedure. In the absence of the resident, the first assistant resident will auto- matically be assigned to the duties of the resident physician. One assistant resident must be on call in the hospital at all times. CHAPTER III INTERNES The work of the internes is subdivided so that each interne will get the greatest variety of clinical and laboratory experience. There are five services which will follow one another in order. Once entered upon, the rotation order cannot be broken but at the beginning of the services exchanges may be made, if mutually satis- factory. The services are: 1. Male Ward. General Medical Cases. 2. Female and Colored Wards. General Medical Cases. 3. P.P. and O.P.D. Private Pavilion Medical Cases and Medical Dispensary. 4. Neurology and Metabolism. All Neurologic and Meta- bolic Medical Cases. 5. Laboratory. Bacteriologic and Serologic Laboratory. INTERNE SERVICE (1) MALE (2) FEMALE (3) P.P. (4) NEUROL. (5) LAB. July 1 Sept. 12 Nov. 24 Feb. 5 Apr. 19 1. Sept. 11 Nov. 23 Feb. 4 Apr. 18 June 30 Apr. 19 July 1 Sept. 12 Nov. 24 Feb. 5 2. June 30 Sept. 11 Nov. 23 Feb. 4 Apr. 18 Feb. 5 Apr. 19 July 1 Sept. 12 Nov. 24 3. Apr. 18 <1 une 30 Sept. 11 Nov. 23 Feb. 4 Nov. 24 Feb. 5 Apr. 19 July 1 Sept. 22 4. Feb. 4 Apr. 18 June 30 Sept. 11 Nov. 23 Sept. 12 Nov. 24 Feb. 5 Apr. 19 July 1 5. Nov. 23 Feb. 4 Apr. 18 June 30 Sept. 11 Schedule of Medical Interne Services The duties on Service 1 and Service 2 will be covered by the gen- eral rules and regulations for medical internes. In Service 3 there are the following additions to the general rules: The private pavilion interne is to meet the physician-in-chief promptly at 8 :30 each morning in the office on the first floor of the pavilion, and is to meet him again at any hour that he requests. This appointment request supercedes all other arranged duties. 26 INTERNES 27 The private pavilion interne is also to go to the 0. P. D. medical clinic at 10 a. m. for the rest of the morning. There is to be an arrangement between the interne and the assistant resident on the private pavilion as to the answering of private pavilion calls and seeing patients with outside members of the visiting staff. In Service 4 there are the following additions to the general rules: Work in Neurology.-The neurology-metabolism interne is to have charge of, and see, all neurological cases throughout the hospital on admission, write orders for the cases and notify the neurological as- sistant resident promptly. Besides seeing that a routine medical history and physical examination are recorded, he is to see that especial attention is given to neurologic details as outlined by the neurology chief. The interne is to accompany the neurology chief and assistant resi- dent on all rounds, and is to make notes on every history whether or not the chief dictates a formal note while he is seeing the case. Any special neurologic examinations are to be carried out that seem indicated. A neurologic examination set is in charge of the assistant resident in neurology. The interne is to do whatever lumbar punctures, special neurologic examinations or other duties are assigned to him by the assistant resident in neurology. Work in Metabolism.-The interne will have charge of cases on the metabolism ward, and will assist on all metabolism cases on the pri- vate pavilion or wards that are under observation or treatment by the director of the metabolism laboratory. The interne will do routine chemical procedures on all ward pa- tients, as for example, blood nonprotein nitrogen, blood sugar, blood COo, complete urine chemistry, two hourly renal tests, concen- tration diuresis tests, basal metabolism, etc., as directed by the di- rector of the metabolism laboratory. He will further be responsible for the recording of such data under the stamp of the procedure in the patient's history. In Service 5 the interne in the laboratory will do such routine bacteriologic and serologic work as ordered by the director of the biological laboratory. The interne will be called at all hours to collect specimens such as blood for cultures, swabs for diphtheria, sputum for pneumococcus 28 METHODS IN MEDICINE groupings, and begin the bacteriologic studies immediately. He will collect and group bloods for transfusions. In cases where bleeding is to be done for therapeutic reasons, the blood of the patient is to be previously or immediately subsequently grouped and examined serologically, bacteriologically and chemically and is to be collected under aseptic conditions by the laboratory in- terne to be used in the transfusion of charity patients or for bac- teriologic culture work. Pleural and ascitic fluids are to be likewise handled. He is to assist the resident in "follow-up" work, obtaining his- tories from the record room and 0. P. D., abstracting them, making notes, writing letters, etc., as directed. General Duties of Internes 1. The interne will visit each new patient on his service as soon as notified of the admission by the head nurse. If he is unable to respond to the call immediately himself, he will arrange to have the assistant resident or resident attend to the patient promptly. At this time a brief account of the circumstances attending and the pur- pose of the patient's coming to the hospital is to be written, and enough history taken and sufficient examination made and recorded as the "admission note" to show the condition and immediate needs. The necessary orders as to emergency treatment, or treatment to be started, diet, bath, T. P. R. interval, etc., are to be given. 2. If the patient is obviously in critical condition, a brief survey of the situation is to be made and recorded and an urgent call put in for the resident physician, who is to be acquainted with the facts of the patient's condition and asked in consultation immediately. If there is any question of the case being an acute surgical condi- tion the resident surgeon is called in consultation at once. 3. In comatose, delirious or critically ill patients, or any that can- not talk or any that are unable to speak or understand English, as much information as possible (in some cases the complete history) is to be obtained from those accompanying the patient on admission, and recorded. The patient, especially if seriously ill, is to be spared the detailed history questioning and any examinations that are not urgent. In case of foreigners, friends of the patients that can act as interpreters are to be summoned. INTERNES 29 4. The interne will promptly fill ont the "front page" completely, with the patient's family name first. The name and address of every patient's family physician, or the last attending physician, or the local physician to whom the patient wishes to have the results of the examination sent, are to be obtained immediately for the front page, and added on the line marked "Physician." This space on the front page is not for the physician-in-chief's name. For example in the case of medical out-patient, "0. P. D.-Dr. C. H. Eyermann," etc., is to be added in this space after the original physician's name and not the dispensary physician's name only, unless the patient had no other doctor within a year. 5. The case is then assigned to a student, who will proceed with the routine work immediately after the posting of the assignment. 6. The interne will see that the complete history and clinical labor- atory report, verified by himself, and his own complete physical ex- amination, including blood pressure, patient's height and weight and the interne's report on a fresh urine specimen, are recorded within 24 hours after admission. The interne will supervise the history of each patient as obtained by the student and will fill out and correct histories in every respect, as to technic, grammar and spelling, and he must verify all interest- ing findings; that is, the interne must examine blood in all cases with Hb. under 70 per cent, r. b. c.'s under three million, leucocytes over twelve thousand, and all obscure cases, and will see and confirm all findings in blood, stomach contents, sputum, stools and all diagnostic or extraordinary findings. Also enter all positive or evident diag- noses on the front page immediately after they are discovered or made; this refers especially to special or instrumental findings by consultants. 7. If the patient has come from the 0. P. D., or has ever been in the 0. P. D. the interne will see that the 0. P. D. history is brought to the ward promptly, as it automatically should be and usually is, and that a brief abstract is recorded in the hospital history. The 0. P. D. history is then retained with the ward history until the dis- charge of the patient, when the discharge note is recorded on both histories and the recommendations as to further treatment and "fol- low up" are to be clearly indicated. 8. The interne will plan with the assistant resident the method of 30 METHODS IN MEDICINE procedure for various examinations necessary to establish a diagnosis and will so arrange and follow up the plans that every patient sent in for diagnosis and not under treatment will have had his diagnostic study complete within 3 days and will be ready for discharge in 7 days, save in exceptional cases. 9. The interne will prescribe for all patients in the ward under his direct supervision. All orders are to be dictated by the interne to the head nurse on the ward. The metric system is to be used in all prescriptions. Pharmacologic names or chemical names of drugs are to be used instead of proprietary names, as indicated in the thera- peutic division of this manual. Only U. S. P. and N. F. preparations are kept in stock in the drug room. Others as New and Non-official remedies must be ordered through the department secretary. 10. He will care for the welfare of his patients, with especial ref- erence to defecation, urination, rest and special conditions, leaving orders for simple procedures, as purges, enemas, sedatives, sympto- matic treatment, etc., p. r. n. and, after consulting the assistant resident, will leave standing orders and special orders as to thera- peutics and management of the case. The general progress of the patient's condition in the hospital, subsequent findings and further developments are to be recorded in at least one daily note by the interne. These notes in the histories must not contain contradictory statements without stating the basis for the reversal of opinion, nor should there be useless repetition of meagre facts day after day. All important symptoms noted by the nurses in the bedside notes must be copied into the histories on the same day. It is a good plan to do this before rounds each morning, and make the note, "night nurse," "day nurse," "special nurse," in the margin with the date and time of the happenings. 11. The interne, or whoever is responsible for the order, will enter promptly with date and time when the procedure is done and not the date of the ordering, under "REMARKS" on the front page, all diagnostic tests or laboratory procedures and operations, such as Wassermanns, N. P. N., etc., P. S. P., Gr. I. fluoroscopies, fractional gastric analyses, gall bladder diagnostics and punctures, with a brief word as to results; and all consultations, with dates, including nose and throat, eye, ear, genito-urinary and skin clinics; requested x-ray plates, films or fluoroscopic examinations; requested heart station INTERNES 31 studies, including exercise tolerance test; metabolism studies, sugar tolerance tests, blood chemistry and concentration diuresis; phar- macologic tests and neurologic examinations. He will be respon- sible for seeing that the details of the results of the tests and con- sultants' answers are noted in the histories, and indicated by border stamps. The interne will see that the hours of all important acts and all special therapeutic attempts are noted in the history under "RE- MARKS" and on the graphic chart, such as hydrotherapy, baking, massage, baths, massive doses of digitalis or quinidin. Medical Teaching Rounds and Clinics 1. The regular schedule of teaching rounds and clinics is posted in each ward and any changes made will be announced. The interne will be prompt at rounds and clinics on his cases, as posted or an- nounced; and will keep a record in his note-book of cases thus gone over. 2. The interne is to have his ward, the nurses and students in readi- ness at 9:00 a. m. for the scheduled formal teaching rounds. The doors are to be closed and the histories at the bedsides. The visit is to be planned so that all cases are seen in the hour, the old cases in the first 20 minutes and the new cases during the remaining 40 minutes. In the former cases the student is to step promptly to the bedside of the patient, give the patient's name, and state concisely what further examinations have been performed and the results; what further data have come to light in the case; what treatment has been carried out, and with what results. AH old cases should thus have been com- mented on in 15 to 20 minutes. Then the new cases are to be taken up in the order of importance, as determined by the resident and interne. The student is to give the history of each new case without reference to the written record. He is to have an abstract, or sum- mary, or notes on a card to which he is to refer. The interne is to correct any errors, mis-statements or omissions. 3. When the patients are being examined by the physician-in- chief, visiting physician, resident or assistant resident, the interne should enter in the history a note of any findings and any remarks or recommendations relating to the study and treatment of the case, stating always whether a formal note was dictated or not. 32 METHODS IN MEDICINE In old or new cases, where there are differences of opinion regard- ing any clinical point, the facts should be stated and steps taken to clear up the situation. 4. The interne will carry a note-book in which to record orders, recommendations, notes and make memoranda of various kinds, dur- ing rounds especially. He will check this book at least twice daily, once after rounds and again late in the afternoon, to avoid over- sights and omissions. 5. The interne will arrange for clinics on his cases as instructed beforehand, and notify the student assigned to the case. The pres- entation of the case at a clinic is to take place in the same way as new cases are presented in formal teaching rounds, completely but concisely. The interne is to record notes, in the patient's history, of the points discussed in the clinic and see that any recommenda- tions made are carried out. 6. The interne will make rounds on all his patients twice daily, once with the resident in the morning and once after the night nurse comes on. Consultation Requests and Other Requisitions Consultations.-1. Requests for consultations are made at the sug- gestion of the physician-in-chief, visiting staff, and resident physician, except in cases of emergency, when any member of the resident staff may act, calling on any consultant. In cases of consultations on ward cases with neurology, dermatology, urology, eye, ear, nose and throat clinics, requests should originate with the interne. 2. In all cases, requests for consultations must be entered in the history, stamped in the margin, giving reason for request and object desired. No space is to be left for the consultant's answer, but the notes are to be entered when made. The interne in charge will be responsible for the prompt response of the consultant, and for secur- ing his opinion, which is to be written into the history, following in its chronological place. 3. When patients need special examinations and treatment in the clinics of the 0. P. D., the interne will arrange for these in person and see that the 0. P. D. consultant is acquainted with the patient's condition. The interne will record promptly official reports of special examinations and treatments in the other departments and enter INTERNES 33 immediately, on the front page, all diagnoses made by consultants in the specialties. 4. All consultation requests, except emergency ones, must be made out by the interne, who is to fill in all necessary data. The slip is to be signed with the name of the physician-in-chief, or the name of the member of the visiting or resident staff who has requested the con- sultation and the interne's initials are to be added after this name. All such slips are to be handed to the resident, who will countersign them and deliver them promptly to the resident of the service from which consultation is requested. 5. In suspected contagious cases, the member of the pediatrics staff in charge of contagious diseases is to be called in consultation by the resident physician, especially if the patient is likely to be transferred to that service, as is the case with exanthemata, diph- theria and mumps. When smallpox, or any other legally quarantin- able disease is suspected, the City Board of Health is to be notified to send out their expert in consultation to confirm the diagnosis and direct the disposal of the case. 6. The interne is to be called by the head nurse and is to see the patient with the consultant, but if so occupied that he cannot re- spond to the call promptly, he is to arrange that the assistant resi- dent or resident perform this duty. The head nurse is to give the patient's record to the consultant and conduct him to the patient while awaiting the attending interne. X-ray Requisitions.-All x-ray requisitions are to be filled out completely, with diagnosis and physical findings, especially in chest cases, on the day the request is made. All of these requests are to be countersigned by the resident, except in emergency and in the case of requisitions for films of teeth. The requisitions for the latter are to be signed by the interne and sent in as soon as he discovers that they are indicated. The requests in all other cases are to be filled out and on the spindle in the ward when the resident makes his rounds, and will be signed at that time. In cases where there is any reason for hurry, the resident may be called or met to sign the requests. (See rules of X-ray Department). Photographs.-Requisitions for photographs are made on x-ray blanks and taken to the x-ray laboratory and studio. All interesting visible anomalies as abnormal bodily forms of endocrine origin, and 34 METHODS IN MEDICINE also tumors, deformities, rashes or skin lesions, scars, pigmentations, hair or skin appendage abnormalities should be sent to the hospital studio for photographs as soon as possible. The requisition must state what is wanted and, if possible, the interne should be present to see that the proper exposure is made. A note is to be put in the history and the margin stamp "Photo" used and the request also recorded under "REMARKS." Good prints are mounted on the regulation size paper and filed and bound with the history. Heart Station.-Requisitions for electrocardiograms and exercise tolerance tests are made out on heart station cards, which must be filled out completely, as to clinical data asked for and must be signed with the name of the physician making the request. A note as to whether the patient is ambulatory or not should be added. Clinical Pathology.-Requisitions for blood chemistry, bacterio- logic and serologic studies, including blood cultures, Widals, blood grouping and matching, tuberculosis complement fixation and Was- sermann reaction tests are to be filled out completely by the interne and signed with the resident physician's name and the interne's initials. The rule of attaching the resident's name is made to insure uniformity and to facilitate distribution, thus preventing the con- fusion of intermingled medical laboratory reports with similar ones from other services. Hydrotherapy.-Hydrotherapy requests are to be filled out by the interne. These originate with the physician-in-chief, members of the visiting or resident staffs and should be signed with the name of the member who has ordered the treatment and initialed by the interne in charge of the patient. In specified cases the member of the senior medical group assigned to the case or the interne in charge of the case is to accompany the patient (in all cases at least one or the other should be present). He is to record observations as to the patient's reaction to treatment, observing general condition, pulse and blood pressure as well as symptoms, before, during and after the treatment. General or Miscellaneous Rules, Notes and Suggestions General Orders.-The interne is to see that all routine house or- ders and special orders are carried out promptly and accurately; viz., 35 INTERNES That all patients are weighed on admission and bi-weekly there- after. That admission urine specimens and two 12-hour specimens for the first 24 hours in the hospital are collected. That admission stool and sputum specimens are collected. That fluid intake and urine output are accurately measured, and charted and checked when ordered. That all contagious and reportable diseases are brought to the at- tention of the Board of Health, and that isolation and disinfection rules are carried out in all infectious diseases. Treatment and Drugs.-The interne will see that all treatment management as well as medication is carried out as ordered. He will see that all orders for drugs are sent to the drug room as promptly as possible, and particularly that all important orders are carried out within three hours. In emergency cases or when orders are given late in the afternoon, the interne must see to it personally that all orders are filled. Critical List.-The interne must report to the resident physician any dangerously ill patient, especially any case that is likely to die suddenly or within a few hours or days. These patients are to be placed on the "Critical List" by the interne after the resident has agreed to the advisability of doing so. In case of emergency this latter condition is removed. In cases in which it is contemplated placing the patient on the "Critical List" and where there is no immediate danger, the interne should see to it that notification of the facts is conveyed to the rela- tives by the hospital office, at a reasonable hour, that is, that the message is not sent to them late at night after they have retired. The preferable way is for the interne to notify the relatives, while they are at the hospital during the regular visiting hours, of the serious- ness of the situation and the possibility of the patient's dying sud- denly, at the same time telling them that the patient is being placed on the '1 Critical List ' ' which permits them to visit the patient at any hour and allows some one to remain with the patient at all times. If this is done, the hospital office must be told that the relatives have been notified. It is especially important to see that a priest is called in all cases where the critically ill patient is of the Catholic faith. 36 METHODS IN MEDICINE Once placed on the 1 ' Critical List ' ' the patient cannot be removed until the condition has improved enough to warrant it. The head nurse on the ward makes out the "Critical Slip" and sends this notification promptly to the hospital office. If the interne has not already notified the relatives in the advised way, the hospital office must do so as quickly as possible after receiving the notice. All patients on the "Critical List" are to be indicated by a black "C" printed on the bed card or on the door of a private room. Transfer or Discharge of Patients Transfer.-Patients who have been sent in by, or to, any member of the staff are not to be transferred to another service, except in an emergency, or discharged from the medical service without the in- terne's having notified the staff member concerned and having ob- tained his opinion in the record. The interne will fill out the regulation hospital forms for the trans- fer and discharge of all patients and have them signed by the resident physician, under whose direction, with suggestions from the physician- in-chief and staff members, transfers or discharges are decided upon. The interne will dictate the transfer and discharge orders to the head nurse and will sign the orders in the order book, just as for any other order. At the request of the chief or resident of another service, who has been called in consultation on any medical case, the patient is trans- ferred to the respective service, as outlined in the preceding para- graphs. A transfer note giving the name of the consultant who advised the transfer, and also the purpose of the transfer, and a short summary of the complaints, history and findings, is then recorded in the medi- cal history by the interne. This note is to take the form similar to that of the "discharge note," which it supplements, but does not replace. On the return of a transferred case, that is a retransfer to the medical service, a complete surgical note as outlined below is to be recorded with a note as to the purpose of the return to the medical service. On all transferred cases, from service to service, to the medical service as well as from it, the original history shall accompany the patient to the new ward and shall be kept in the folder in its regular INTERNES 37 order with the new history, but behind the yellow admission folder. The original history is to be retained for a few days for reference and during this time the regular abstract shall be made as usual for the new history. When the history of a transferred case returns to the medical service and is to be completed for the regular history meeting, to be diagnosed and filed, a complete surgical (etc.) note is to be written recording the findings and results of operative procedures, etc., and the convalescence of the patient. The "discharge note" is then to be added. If the patient dies and postmortem examination is made, an "autopsy note" recording the gross pathologic findings is to be added to the medical history, even though the patient died on another service. Discharge.-When the patient is ready for discharge, which in cases admitted for diagnosis only should be within 5 to 7 days after admission, the interne will advise the assistant resident or resident and upon the assent of these the patient will be given full instruc- tions and advice, and discharged. The interne will promptly and before the patient leaves enter a "discharge note," which should record the status praesens with reference to the primary complaint, chief symptoms, complete diagnosis, treatment, course in the hos- pital and advice. At the same time in the 0. P. D. history should be noted the duration of the patient's stay in the hospital, the diag- nosis, results and advice as to further treatment and "follow up" and any other remarks. The 0. P. D. history must be returned promptly to the 0. P. D. When the discharge of a patient is requested against the physi- cian's advice, by a relative, friend, or the patient himself, and the illness is serious or such as will demand immediate further medical care, the interne, assistant resident or resident must fill out the "certificate of release" form and have it signed by the person re- questing such discharge, and by a witness, and he shall sign it as a second witness. The hospital history and the 0. P. D. history must be sent to the hospital record room immediately after the patient leaves the ward. The 0. P. D. history is inspected by the record room staff and if it is found that no abstract has been added, the resident will be notified and he must see that the negligent interne goes to the record 38 METHODS IN MEDICINE room and makes the abstract. The 0. P. D. histories must not be retained in the record room more than 24 hours. The hospital history is not returned but is accessible to the interne until the following Saturday evening, that is, three days before the history meeting, which is held at 12 :00 noon each Tuesday. The interne must complete and correct the histories, complete the list of diagnoses on the front page and add the International Classi- fication numbers, and then place the finished histories in the hands of the assistant resident on time so that he can lopk them over and have them on the resident's table on Monday night. Interesting preparations, such as blood smears, etc., must accompany histories properly labeled, dated and numbered. The histories of transferred cases must be sent with the patient to the other service (See Record Room Rules). Autopsy.-In making efforts to obtain autopsies, two members of the staff should take part. The older or more experienced man, especially one known to the relatives, should make the request, the younger or less experienced man to make notes of important state- ments, get signatures and observe the conditions that obtain at such time. The interne is to ask the assistance of the assistant resident, resi- dent, physician-in-chief or superintendent in obtaining consent for autopsies, if he needs support in obtaining permission. In all cases where permission to have autopsy is not granted, a note to this effect is made in the history stating the reasons for re- fusal. If permission has been granted and autopsy is not done, the reason for failure to do the autopsy must be stated. On all cases coming to autopsy, the interne or his substitute must be at the autopsy to give clinical data, to post and record the black- board diagnoses, and to note the gross findings and see that interest- ing points are cleared up, and record them in the autopsy note, which is to follow the discharge note. In cases coming to autopsy the interne will promptly prepare and sign an abstract following the suggestions given out by the depart- ment of pathology. Three copies of this are to be typewritten, one for pathology, one for the record room and one for the interne. The interne must see that the causes of death put on the death INTERNES 39 certificate by the assistant resident are recorded in the history in a proper note. Statements, Etc.-The interne will see that the statements to patients regarding diagnoses, prognosis, consultations, operations, etc., are noted in the history at the time, with the patient's response also noted. Statements to relatives regarding important facts as above, should likewise be written in the history. Also remarks of relatives. Letters, Etc.-Letters are to be written to each patient's doctor within five days and again on discharge. These letters must be handed to the assistant resident, resident, or physician-in-chief, for editing before being sent. Copies of all letters about patients are to be filed with the history. Instruments and Laboratory Equipment.-The interne will be re- sponsible to the assistant resident for all instruments, and the repair of same, on the ward and for supplies and for the card index of spe- cial apparatus. He is also directly responsible for the equipment and supplies, and the general condition of the ward laboratory. He will be given an inventory, which must be checked up and handed to his successor on the ward each time there is a shifting of internes, that is, about every seventy days. Miscellaneous The Manual.-Each interne will receive a Manual of the Medical Service as a reference book, for this he will sign in the physician-in- chief's office. He is responsible for the book and must check it in before leaving the hospital. It is the property of the department and its loss will cost the responsible interne the sum of $25.00. (This applies to manuscript copies). Important Hours.-The interne is to be on the wards at the visit- ing hours to talk with patients' relatives and friends. At least two internes must be on call in the hospital at all times. Answering of Calls.-When a member of the house staff wishes to absent himself from the hospital, even though for only a short period of time, he must speak with another member of the house staff, asking the latter to answer his call number on the telephone or his name on the musolaphone. In asking the favor of another member 40 METHODS IN MEDICINE he must always repeat his telephone call number, so as to insure results. The absentee must sign out in the book in the hospital office, and besides his name and the time, he must put down the name of the member who has consented to be signed in, and is to mention the facts to the operator at the switchboard. On his return he must sign and report in. In case the absentee is leaving the hospital for a very short time only, the one signed in can take messages for him and state his where- abouts and the approximate time of his return. The Central Medical Supply Room There has been established within the department of internal medi- cine a supply division, which has been placed under the supervision of the director of the bacteriologic laboratory, but which is separate and apart from the biologic chemical division or any other division in the department. The object of the establishment of this division is to centralize the ordering and distribution of supplies, the con- servation of property belonging to the department and the prepara- tion of standard solutions used in the ward laboratories, in teaching and by other departments. This room will be open for the withdrawal of supplies from 9 to 5 o'clock daily, except Saturday and Sunday. It will be open from 9 to 12 o'clock on Saturdays, but will be closed on Sundays. In case material is wanted for an emergency at hours when the stock room is closed, access may be had to the room by applying to the resident physician. Members of the staff should endeavor to secure supplies in advance of the closing hours. Whenever supplies are withdrawn from the stock room a receipt for the supplies must be given to the clerk in charge. This receipt will be held until the supplies are returned or until the account is settled. In order to facilitate the working of the division, all orders for supplies other than stationery and books will be forwarded to the head of the department through the clerk in charge of the supply division. The object of this ruling is to insure that the stock of re- agents and chemicals is kept up to the proper requirements, that material which is ordered is received in good condition, that an ac- INTERNES 41 curate inventory of property may be kept, and that an accurate ac- count of what each division of the department is spending may be available for future budget estimates. It is not contemplated that the supply division will act as censor over such orders in any shape or form. It is expected that the division will act as an agent only, and as a channel for facilitating the securing and distribution of the necessary supplies. One aim of the division will be to keep on hand at all times a rea- sonable stock of materials and apparatus being used by the various departments. The success of the scheme as outlined will depend largely upon the cooperation of all members of the staff. Unless this is forthcoming the workers in the department will be handicapped in their work. Arrangements for Obtaining Supplies.-Anyone in the department needing reagents or apparatus of any kind will apply as above. If informed the material is not on hand he should make out a requisi- tion stating the exact name, if possible catalog number, dealer, and purpose. This will be approved by the director of the laboratory in which the individual is engaged. The request will then go to the department secretary, who will ascertain whether the goods are not in stock, and if not, will make out an order and submit it to the head of the department for approval. Time will be saved by trying to be sure the article needed is not already in the supply room. CHAPTER IV RECORD ROOM RULES By Miss Elizabeth Green General Routine for Clinical Histories Record room hours 8:30 a.m. to 5 p.m., except Sundays and holi- days. Persons Entitled to See Histories.-Histories are accessible to the hospital and house staff, superintendent, assistant superintendent, superintendent of training school, head of social service, and students who are doing work in the hospital and are assigned work on ab- stracts, class work, or special work for some member of the staff. Doctors of the 0. P. D. staff can also consult hospital histories of 0. P. D. cases, but all other persons must obtain permission of the superintendent. Rules for the Use of Records.-No history may be taken from the hospital save on a summons to court. Histories must not be taken from the ward, but must remain there, until the patient is dis- charged. All records of discharged patients must be in the record room by 5 p. m., unless provided for under other authorized rulings. Under no circumstance may a history be tiled by any person other than a member of the record staff. Students must do their abstract- ing in the record room, except on transferred cases, where the his- tory accompanies the patient to the new ward. On transferred cases, the student makes the abstract on the ward. No history may leave the record room unless signed for by some one privileged to sign for it, and then only under authorized rulings. Nurse's Routine.-The nurse shall see that the patient's record is sent to the record room as soon as the patient is discharged. Should the nurse discover an error in the graphic chart, she may arrange with the record department to withhold the page or pages needing correction, but such correction must be made and the part withheld must be sent to the record room within 24 hours. The nurse's obliga- tion in this routine is with the record department and not with the 42 RECORD ROOM RULES 43 interne who is not privileged to ask a nurse to hold out a history to serve his convenience. Internes' Routine.-Internes may work on records in the record room during record room hours. All abstracts of previous admis- sions are to be made in the record room, unless a special emergency makes it desirable to allow an interne to sign out for the history. History meeting is held once a week by each service, preferably on Monday or Tuesday. AU histories of discharged patients are kept accessible in the record room until required for history meeting. Histories that have not been through history meeting, may be taken out in order that the internes may complete their histories before history meeting. Such histories may be signed out for after 4:30 p. m. on Saturday, if the history meeting is not later than Tuesday. All histories shall be on call by the record department, should they be needed. The interne in charge of a ward is responsible for the histories from his ward, from the time they are signed out from the record room, until they are turned over to the resident, after history meet- ing. The resident then becomes responsible for all histories out for his meeting, and he shall see that they are given to the service stenog- rapher promptly, whose duty it is to type the front pages, number the histories, etc., and return them to the record room, at the earliest possible moment. The resident's responsibility for the safety and preservation of all histories out for history meeting ends only when such histories are returned to the record room as completed histories. A duplicate list is furnished the resident of all histories sent out for history meeting on his service. Histories must be kept in a safe place, preferably a drawer in an interne's desk, during the time that they are being prepared for his- tory meeting. Histories must be written up from day to day, so that the history when turned in to the record room at the time of the patient's dis- charge is practically a completed history. Internes can arrange with the record department for a special piece of work, that cannot be done in record room hours. The record force will see that the histories required are ready for the interne, and he is privileged to sign out for such histories overnight, the night he desires to work on them. 44 METHODS IN MEDICINE Visiting Staff.-Members of the visiting staff may use the record room at night, by arranging the matter with the record keeper or assistant record keeper. The visiting doctor must state what histories are desired, and what night he desires to use them. The histories requested shall be left on a table in the record room on the night selected, marked with the doctor's name. A letter addressed to the doctor, with the key to the record room enclosed, shall be left at the front office with instructions to deliver it only to the doctor addressed, and for that date only. The letter shall give instructions as to such points as seem best to the safety of records, such as locking the door while using the record room, and not admitting anyone, seeing that all windows are closed, the lights turned out, the door to the record room is locked on leaving, and the key posted through the slit in the record room door. It is desirable that arrangements for this special use of the record room should be made a day or two ahead, so that the regular work of the record department shall not be too greatly disarranged. Borrowing.-Histories may go to a ward for rounds, to a clinic for class demonstration, or on the signature of a chief of a service or department of a service, may go to the 0. P. D., when sent for by a suitable person. The 0. P. D. page service is available for this, and the person signing for the history is responsible for it until its re- turn to the record room. Emergencies, Night.-The night supervisor is authorized to open the record room to a doctor needing to consult a previous admission of a case brought in as a night emergency. A box plainly marked, 'will be found on the record room desk, con- taining a key to the record room, a letter of instructions to the doc- tor, and a description of the use of the name index. The night super- visor is to give the emergency key and letter of instructions to the doctor, and when she leaves the room, the doctor is to lock himself in, and after consulting the history, is to follow the instructions per- taining to the locking up of the record room, posting the key through the slit in the door on leaving. Emergencies, Sunday and Holidays.-Should a history need to be consulted on Sunday or a holiday when the record force is absent, the superintendent or assistant superintendents will carry out the same procedure as the night supervisors. RECORD ROOM RULES 45 Abstracts.-All abstracts should be brief and cover essential points only. Abstracts of Re-entry Cases.-Abstracts of previous admissions are to be included in the new history of a re-entry. Abstracts for Transfers.-An abstract is to be made of the history of the patient on the service from which the patient is transferred, for the new history: i. e., a patient transferred from medicine to surgery shall have a medical abstract in his surgical history. Abstracts 0. P. D.-An abstract of the patient's 0. P. D. history must be made for the hospital history. The 0. P. D. history is kept on the ward with the patient's hospital history until his discharge, when it goes to the hospital record room attached to the hospital history. The hospital record room force inspects the 0. P. D. history, and if an abstract of the hospital ad- mission has not been made, the resident of the service concerned is notified and he sends the interne responsible, to the hospital record room, to make the abstract. This should be done within 24 hours, but must be done within 48 hours, in order to get the 0. P. D. history back to the 0. P. D. record room within the time agreed upon. This rule is made to conserve the best interest of the patient. Transfers.-When a patient is transferred from one service to another, the transfer blank is to be made out by the interne and signed by the senior resident on that service, on the line following "Signed." It is then brought by the nurse to the office and the date inserted on the second date line, and the name of the superin- tendent signed on the line ending "M.D." by the person in charge of the office. All cases where operative procedures are indicated shall be trans- ferred, with the following exceptions. Slight operations for the purpose of diagnosis, where after-care is unimportant. Examinations under anesthetic. Cases in which the technical operative procedure is incidental to continued medical treatment: i. e., transfusion, intraventricular serum injection. The history shall go with the patient and shall be kept in the folder with the new history for reference. The new history shall contain an abstract of the accompanying history. 46 METHODS IN MEDICINE The history that comes with the patient from the service from which the patient has been transferred, may be called for if needed, by the record department. No other department or person may remove the history from the ward. Form 115 5M-4-17 C. BARNES HOSPITAL TRANSFER NOTICE DateJune 1,19.21 191 Nurse must send to office before making Transfer Name Smith, Sarah No. 11453 Ward -2219 (Surgery) Has been seen by D r Dock Please transfer toMedici ne(1418> kTigned Copher Date June 1,.. 1921 OFFICE,-Forward to Record Room Miss Jones Miss Brown L, H. Burl Ingham M. D. H.T.S. Certificate of Release.-When a patient is discharged against ad- vice, the certificate of release is to be made out. The person re- sponsible for release signs on the line indicated. Signatures of two witnesses go on the line for that purpose. Autopsies.-The resident of the service on which a death occurs, or the interne in charge of the ward, sees the nearest relative, and if an autopsy is granted, two copies of the autopsy permit are made out. Both copies must be signed by the person authorized to grant the autopsy. The resident or interne who writes the autopsy permit, signs his name on the line following "Dr.", and writes "Yes" or "No" as the case may be, after "Should this be a coroner's case?" No post- RECORD ROOM RULES 47 mortem can be made on a coroner's case without his permission. If an examination of the brain and spinal cord or of the neck organs is desired, a special request for this must be made of the nearest rela- BARNES HOSPITAL CERTIFICATE OF RELEASE st. i ouis, Junel, 1921 TO WHOM IT MAY CONCERN: THIS IS TO CERTIFY THAT 1 HAVE BEEN FULLY INFORMED AS TO THE COt.DiTION OF Mary Jane Smith (NAME) DISCHARGE FROM THE BARNES HOSPITAL, AND THAT I HEREBY RELIEVE THE BARNES HOSPITAL OF FURTHER RESPONSIBILITY IN THIS CASE signed John Smith RELATIVE OR FRIEND REMOVING PATIENT RELATION TO PATIENT Husband G. H. Copher C. H. Briggs WITNESSES WHEN THE DISCHARGE OF A PATIENT IS REQUESTED BY A RELATIVE, FRIEND OR THE PATIENT, AND THE ILLNESS IS SERIOUS, OR SUCH AS WILL DEMAND IM- MEDIATE FURTHER MEDICAL CARE. THE RESIDENT OR RESIDENT ASSISTANT PHY- SICIAN MUST FILL OUT THIS "CERTIFICATE OF RELEASE" AND HAVE IT SIGNED BY THE PERSON REQUESTING SUCH DISCHARGE, AND HE SHALL SIGN IT AS WITNESS. 7-19-IM-Form 54. five, and the facts written on the permit with the word "complete" inserted. Likewise any restrictions promised must be written on the permit. 48 METHODS IN MEDICINE One copy is then presented to the superintendent with the author- ization permit also attached. The latter is signed by the superintend- ent, thereby authorizing the autopsy, and then it is transmitted to the pathological department. One copy of the autopsy permit is retained in the front office. The other copy is turned in to the record room by the interne, to be attached to the history. The resident notifies the Coroner of cases which come under his juris- diction, after reporting the case to the superintendent or his as- sistants. The remains of the patients who die in the hospital are in the custody of the superintendent of the hospital. CHAPTER V X-RAY DEPARTMENT RULES By Dr. Sherwood Moore No patient will be received in the x-ray department for whom a requisition has not been furnished. When ready, the department will phone to have the patient sent to the laboratory. Requisitions.-Requests for x-rays, etc., must be in not later than 1 o'clock of day on which same is desired. Those received after 1 o'clock will be taken on the following day. Requisitions may be de- posited in the box at entrance to x-ray department or may be left in the office of the department. Requisitions must be completely filled out as to the following points: patient's name in full (Christian name as well as surname), address, color and sex, etc., hospital number, service (if private pavilion state P. P.), whether patient is to pay or whether to be charged to the service, clinical diagnosis and the x-rays desired should be specifically stated. Requests for special examinations, treatments or photographs should be made on separate requisitions. In cases where lung or heart plates are desired a note of the physi- cal findings must be added to the requisition, and a note of these findings recorded in the history on the day that the plates are made. Hours.-Routine x-rays of hospital and private pavilion patients will be taken between 2 o'clock and 4 o'clock in the afternoon (ex- cept Saturday, on which day same will be done in the morning). Exception is made in cases of emergencies, which will be given pref- erence, and of pyelograms (see below). Pyelograms will be done in the morning between 9 :30 and 10:30 o'clock. Please phone x-ray room for appointment (if possible, the day previous.) If the requisition has not been furnished previously, same must accompany the patient. Fluoroscopic Examinations of Chest will be done in the afternoon between 2 o'clock and 4 o'clock. Please phone x-ray room for ap- pointment. 49 50 METHODS IN MEDICINE PhotogTaphs and Prints.-Photographs will be made by the pho- tographer in the x-ray department. Requisitions must be properly filled out, stating specifically what is desired and the circumstances. The patient wid be called by the x-ray department. Unless other- wise stated photographs will be charged to the service requiring the same. A print will be made from each photographic plate and delivered to the record room of the hospital for the patient's his- tory, and will also be charged to the service. X-ray Treatments.-Treatments will be given in the afternoon only. Appointments will be given upon recpiest; if not requested, however, the patient will be called on earliest date possible. Emergencies.-The urgency of the patient's symptoms alone con- stitutes an emergency. Forgetfulness on the part of the house staff, their convenience or the patient's convenience does not constitute an emergency. Emergency cases on Saturday afternoon, Sunday, or at night before 11 o'clock will be taken care of either by the tech- nician or the director of the x-ray laboratory, arrangement between them being that if one is out of reach the other will be on telephone call. Emergencies after 11 p. m. will be taken care of by the direc- tor of the x-ray unit. Outside Cases-Treated in the Surgical Dressing Room.-If an x-ray is desired, unless an emergency after dispensary hours, the patient, if poor, should be sent to the dispensary from which source the request for x-ray should be made. This procedure is desirable on account of the 0. P. D. history, fee, etc. If the case is not to be a dispensary case, patient will be treated as a private patient and charged according to ability to pay. Preparation Fluoroscopic Examinations of Gastrointestinal Tract.-Upon re- ceipt of requisition requesting such examination, appointment for earliest possible date, with printed instructions for special prepara- tion, will be sent to ward. Patient will be allowed but one-half piece toast and one small glass of water not later than 7 o'clock on morning of examination-unless otherwise instructed-and may have no purgative or enema. Patient is to be sent to x-ray room at 11 o'clock. After the initial and each subsequent motility observation, instruc- tions will be inserted in patient's chart, and when examination is X-RAY DEPARTMENT RULES 51 completed it will be so noted in the chart. If the request is for barium enema examination, only, special instructions as to preparation will be given, i. e., purgatives and enema. (Note) A specific clinical diag- nosis should be stated, if possible, on all requisitions for gastrointes- tinal examinations, or, at least, symptoms given. (Note) Requests for gastrointestinal examinations should be given as far in advance of time desired as possible, since it is sometimes necessary to give appointments for dates a week ahead. X-ray of Urinary Tract.-Patients for plates of the urinary tract are to have a laxative (not a saline) the preceding night, and an enema on that morning. X-ray of Gall Bladder.-Except when taken in connection with a general gastrointestinal examination, patients for plates of the gall bladder are to have a laxative (not a saline) the preceding night and an enema on that morning. X-ray Reports.-Reports will be furnished on all x-ray plates and fluoroscopic examinations. Such reports, covering plates of the pre- vious day, will be distributed to the wards, etc., daily. (Note) Re- ports of gastrointestinal examinations will be submitted on the day following last observation. Unsatisfactory Plates.-Plates which are technically unsatisfac- tory will be retaken, and a request to have the patient return will be noted on the report. In such cases a requisition marked "Retake" should be furnished and the patient will then be called to x-ray in the usual manner. Personal Examination.-Plates and films may be seen in the x-ray room on the morning of the next day after taking. Plates of emer- gency cases will be developed immediately. Removing Plates from X-ray Room.-Upon application to the plate clerk, plates may be removed from the x-ray room after noon of the day following the x-ray. Such plates must be returned promptly-the same day if possible. (Note) An exception to the above rule is made in favor of operative cases. New plates needed in the operation room will be delivered when called for, but must be returned immediately. (See note below regarding old plates.) Removing Plates from Hospital.-Plates may not be removed from the hospital except when required by a staff physician as court 52 METHODS IN MEDICINE evidence. Under such circumstances said physician is expected to return plates promptly. Old Plates.-Requests for old plates, (i. e., more than four months old) should be made a day in advance if possible. When a large number of plates are desired for study a notice of several days should be given. Prints will be furnished the patient from his plates at a nominal fee. Dental Films will be delivered to the patient when desired and need not be returned, as duplicates are retained in the x-ray room. No x-ray plates will be shown by the personnel of the x-ray depart- ment to patients, either while in or after leaving the hospital, unless so requested by the house or staff doctor in charge of the case. Under no circumstances will plates be shown to any stranger except the physician treating the case. X-ray Findings, except on dental films, will not be given out by the x-ray department unless at the request of the house or staff physi- cian who had charge of the case, except to another physician who has taken charge of the case since the patient's discharge from the hos- pital. With this exception, all requests for reports on findings on x-ray plates will therefore be referred by the x-ray department to the house or staff physician. (Lawyers desiring reports are advised by the x-ray department that a written request from the patient will be required, to be addressed to the physician.) Students, Nurses, and Employees requiring x-rays, unless a pa- tient, in the hospital, should make an appointment with the x-ray room. If the x-ray is not to be paid for by a department or the hos- pital, charge will be made to the patient at cost. The x-ray department is open every day except Sundays and holi- days on which the dispensary is closed. X-rays are not taken on Saturday afternoon, but information relative to plates, reports, etc., may be obtained in the x-ray office. CHAPTER VI SUPERINTENDENT'S RULES By Dr. L. H. Burlingham Some Important Things for House Men to Remember Do not give out information to newspapers, lawyers or insurance men. Refer any such inquiries to office. Do not fill out any forms, sign or witness any papers unless author- ized by the superintendent on duty. Refer any inquiries in regard to extra visiting privileges and finan- cial matters directly to the office without any expression of personal opinion. Do not smoke or wear hat in the rotunda, halls or other public parts of the hospital. Do not sit on desks and do not use nurses' desk. Do not sit on patient's bed unless making a definite physical ex- amination. House men who are not on a particular service attending a sick nurse are not to visit her, except with the permission of training school office. Keep your critical list up to date. Make all records exact, com- plete, and dignified. Report promptly any unusual occurrence to the superintendent on duty, as, e. g., an unexpected death. In giving out information in regard to patients, be honest with their friends, but tactful. When you talk with the nearest relative of a deceased patient, be sure they understand what they are doing when they sign permis- sion for autopsy. Do not accept any fees from patients. Do not do routine work on wards after 5 p. m. 53 54 METHODS IN MEDICINE Coroner's Cases Report immediately to the resident physician, who in turn is to report to the coroner any case coming under any of the following heads: All deaths resulting from accident or injury. All deaths occurring suddenly without MEDICAL ATTENTION. All deaths resulting from peritonitis following abortion or miscar- riage. (These cases should be reported to the coroner's office as soon as observed.) All deaths occurring where eases have not been observed for 24 hours. All deaths following SHOCK or ANESTHESIA during operation. All deaths following BURNS. All deaths following POISONING. All deaths following SUICIDE. All deaths wherein a FELONY or CRIME is involved. ALL STILLBORN BIRTHS not delivered by a REGISTERED PHYSICIAN. Advisable Route for Showing Visitors about Hospital Rotunda to colored ward; by elevators to third floor, to operating suites and chapel; down stairs to second floor, to record room, oc- cupational therapy office, metabolism and x-ray, pass male medical ward to social service, to heart station, and down corridor by lab- oratories to stairway; to first floor dispensary; to basement dis- pensary; back to hydro-mechanotherapy, to drug room, to shops, store room, kitchen, back to Sewing room to Junior League Work Shop, to private pavilion kitchen; by elevator or stairs to 1st floor private pavilion, to male surgical ward, to Trustees' room, to rotunda. Mention that Children's Hospital is separate institution though affiliated with this hospital and give directions to Children's Hospital if desired. CHAPTER VII GENERAL DIRECTIONS FOR MEMBERS OF THE SENIOR STUDENT GROUP IN MEDICINE 1. Students are issued complete sets of laboratory apparatus, as described under "Laboratory Equipment for Ward Workers" (Plan for Conduct of Ward Laboratories), provided with laboratory lock- ers and assigned, alternating alphabetically, to the male and female wards, including the metabolism unit and the colored ward. 2. An alphabetic list of the students working on the wards (to which each student is expected to add his telephone number) will be found in a conspicuous place in each ward laboratory. On this list are posted the names of the patients as they are assigned to each student. New patients are assigned in rotation and by watch- ing this list, students can tell when they will receive a new patient. Students should make inquiry in person or by 'phone, when the new case will be ready on the ward. By this means no time will be lost in seeing a new patient. 3. When a patient has been admitted to the ward, the interne will fill out the front page, assign the case to the proper student and use ordinary means to notify the student. However, the latter will be held responsible for knowing when new cases are admitted. 4. The wards are open at 8 :00 each morning. Students are not expected to attend the patients during meals, hours from 12 to 1 p. m. and 5 to 6 p. m., or during the visiting hours from 1 to 2 p. m. By 6 p. m. the day's work on the ward should be finished and no one should return to the ward. When emergencies exist this rule may be waived, but otherwise students are requested to observe it. 5. As soon as possible after admission, a complete history should be obtained from every new patient, according to rules and guides laid down elsewhere. (Sec History Taking Notes and Suggestions.) 6. As soon as possible, the student should make a physical examina- tion of his new case, preferably before the interne makes the routine examination, though this must be arranged to suit the convenience 55 56 METHODS IN MEDICINE of the interne. When the interne makes his examination, the student is expected to take his dictation. 7. Writing paper and record material will be found in the drawers of the laboratory desks and all writing other than that done at the bedside, is supposed to be done on the laboratory desks. The nurses' and house officers' tables are not to be used by the students. His- tories may not be taken from the record room or hospital ward under any circumstances. Access to histories in the record room may be had only on written order from the resident or assistant resident in charge. 8. When the history and physical examination have been com- pleted, or before, if necessary and possible, the routine laboratory studies should be attended to. All of this work must be completed before "Rounds" the next morning at 9 o'clock. Every precau- tion must be taken during and after the examination of any sus- pected infectious case, or specimen from such a patient, to prevent self contamination and the spread of the disease. 9. When the student makes a physical examination of his patient and finds anything overlooked, new or differing in any way from the routine examination, he should make a new note of his own, giving a clear description of what he has found, and as soon as possible inform the interne. Subsequently he is supposed to see each of his cases at least once daily or oftener, if the condition warrants it, acting in the capacity of "family physician," following the physical conditions, symptoms, and general moral or mental status. When anything new develops he should notify the interne at once and make a note. The student must develop and practice the art of medicine by buoying his patient up, when the spirits seem low, instilling good cheer and encouragement, and inspiring confidence. However, the discussion of medication and treatment must be diplomatically but definitely avoided. He will be held responsible for knowing of all special and routine treatment in each of his cases. Standing orders will be found on the temperature chart, the routine and "stat" or- ders in the order book on the nurses' table. 10. It is expected that each student will be on the ward promptly at 9 a. m. for "rounds." Each one should be perfectly familiar with his histories and be able to give the history and physical findings without referring to the written record. The record should be in the GENERAL DIRECTIONS FOR SENIOR STUDENT GROUP 57 hands of the visiting physician or house officer. It is expected that the students will stand during rounds; not sit in chairs or lean or sit on beds. 11. When cases have been selected for presentation in conference the student in charge will be notified by the interne as soon as pos- sible so that he may complete all examinations beforehand. At the conference he should, when presenting the case, have the written record in the hands of the interne and tell the story, standing near the patient. He must be prepared to give the findings of importance on physical and laboratory examinations, and to discuss the path- ology, diagnosis and treatment of the case. CHAPTER VIII HISTORY TAKING AND PHYSICAL EXAMINATION NOTES AND SUGGESTIONS "Outlines for Case-Taking" (third edition) by Dr. George Dock,* Professor of Medicine and Physician-in-Chief, is the basis for the construction of medical histories. The following suggestions, mostly repetitions from the book, will call attention to points that have been, at times, subject to error. During the taking of a history at the bedside, the "Outlines" are to be referred to for suggestions and points to be emphasized, and details to be obtained and observed when the patient's complaints and subsequent statements suggest a line of investigation, such as: I. Acute Infectious Diseases. II. Diseases of the Respiratory Organs. III. Diseases of the Circulatory Apparatus. IV. Diseases of the Organs of Digestion. V. Metabolism, Blood, and Ductless Glands. VI. Urinary and Sexual Organs. VII. Nervous System. Front Page.- 1. Last name first. 2. Omit "Mr." and "Mrs.", etc. 3. Put your name on line "History taken by" if case is as- signed to you. 4. Enter hospital number. This is on yellow folder. Leave blank medical number. 5. Obtain "former admissions" and dates from record room and enter same with diagnoses in proper space on front page. 6. Full name and address of physician sending patient into hospital, family physician or last attending physician. ♦Published by George Wahr, Ann Arbor, Mich. 58 HISTORY TAKING AND PHYSICAL EXAMINATION 59 7. Place on front page is for above (6) and not for the physi- cian-in-chief 's name. 8. If patient comes from 0. P. D., write "0. P. D.-Dr. Eyer- mann," etc., as patient's physician, unless the patient has had an outside physician within a year, in which case, both the outside and 0. P. D. physicians' names should be recorded in this space (6). History Proper The patient's story is to be taken down as notes in pencil with good, free margins and interlinear spaces left for the insertion of later recalled events, which are inevitable. The patient's memory is to be refreshed with questions about the various system symptom groups until a complete chronological story with especial reference to the de- velopment of the patient's illness is obtained. Reconstruction and rewriting of this data will form an acceptable history. Admission Note.-Circumstances of the patient's entrance to hos- pital and his condition, especially when comatose or incommuni- cable, are to be recorded. Complaint.- (See Part 1, Section 2) Not only the chief complaint, but other complaints and symptoms from which patient seeks relief, e. g., not "pain in side," but rather "sharp cramp-like pain in left upper abdomen." The diagnoses of previous physicians, as "Gall- stones" or such meaningless terms as "Torpid Liver," etc., are never to be used. Past History.-(Previous Diseases or Condition) (See I, etc.-5). Condition from infancy in chronologic order. Ask about various childhood diseases mentioned in Section 5. Follow patient's career chronologically with questions about the enumerated diseases of in- fancy, childhood, adolescence, and manhood or womanhood. Note the points mentioned. Present Illness.-(Present Disease and Symptoms) (See I, etc.- 8, 9, 10, and 11). Obtain a complete chronological, not merely a symptomatic, story of the development of the patient's illness from the first day and symptom to the day of admission and the present- ing complex in detail. Each symptom must be developed completely according to the suggestions in Sections 8, 9, 10, and 11 of parts II, III, IV, V, VI, and VII, as for example, in II Respiratory Organs,- 60 METHODS IN MEDICINE Pain in thorax; duration; location; character. Cough, time of occur- rence; character; etc. Avoid leading questions, and the suggestion of symptoms, if possible. When any patient's complaints or subsequent statements suggest a line of investigation, such as II. Diseases of Respiratory Organs, III. Circulatory apparatus. IV. Organs of digestion, V. Constitu- tion or metabolism, VI. Urinary or genital tract, VII. Nervous sys- tem follow the suggestions indicated in the "Outlines" under the appropriate section. Note numbers II to VII. Present Symptoms.-Part I, Section 10. Do not omit this sum- mary. Diagnoses from History.-Logical deductions from the symptom- atology and the clinical course as given in the history are to be made and recorded. Make brief marginal notes in red calling attention to important points in the history. The latter may be underscored in red to ad- vantage, if care is taken not to underscore too much. Avoid negative statements except where important to a proper understanding and of definite negative etiological significance. Do not remove histories from bed-side. Physical Examination.-Follow outline of statics praesens in the "Outlines for Case-taking." General External Features.-Do not use such terms as "well de- veloped and nourished" or its abbreviation (W. D. & N.) or such statements as "no general glandular enlargement" or its abbrevia- tion (No G. G. E.), but use definite terms as to frame, habitus, mus- culature and nutrition in terms of size and condition; also size and character of lymph glands in the cervical, axillary, epitrochlear and inguinal regions. Condition of skin and mucous membranes, bones and joints, super- ficial and deep reflexes. Psyche, i. e., general mental condition, reaction to surroundings and questions. Condition or state of organs supposed to be affected, in order. Head.-Anomalies. Eyes, ears, nose and throat, with notes as to mouth, tonsils, teeth and gums. Neck.-Describe especially the thyroid gland. Chest.-Lungs and pleurae, pericardium and heart, both organi- HISTORY TAKING AND PHYSICAL EXAMINATION 61 cally and functionally. Condition of pulse, arteries and veins. Blood pressure in arms and legs. Abdomen.-Level, panniculus, patterns, abnormal peristalsis, tu- mors or rigidity. Condition of spleen, liver, gall bladder, gastro- intestinal canal, appendix, cecum, colon and rectum. Kidneys, bladder, genitals, as to condition of gonads and prostate. Uterus and adnexa. Sites of hernia. No mention of an organ indicates that it has been examined and found normal. Regional Abnormalities are to be carefully sketched, and measure- ments in centimeters indicated, on the diagrams that can be stamped on the history paper at the proper place that the organ or region takes in the regular order of the physical examination. Photographs arc to be taken, in all cases in which they can usefully supplement descriptions, or are otherwise interesting. Abstracts of 0. P. D. History When a patient conies from the out-patient department, enter a comprehensive summary (not an abstract of F. H., P. H., etc.) of the 0. P. D. record, stating reasons for the patient's entrance into the hospital. Unnecessary details should not be copied. The most important data, complaints, physical and laboratory findings, treat- ment and course under treatment should be recorded. If x-ray studies, electrocardiograms and other special examinations have been made, copies of reports are to be secured for the Hospital History. Side Headings and Paragraphs.-In the history and physical ex- amination, each new organ or topic should begin a new paragraph. This should be written so that the new topic shows plainly on the space at the left-hand side. The interne, when writing the history, and those who write the his- tory and physical examination after that, should write in the left- hand space, words indicating the important facts stated in the text. This is particularly important in the case of matter outside of the usual order, such as additional history, also consultations and requests for diagnostic and therapeutic measures ordered or carried out. The Notes and Diagnoses 62 METHODS IN MEDICINE rubber stamps and red inking pads are to be used throughout the history. Diagnoses.-One of the chief objects in the handling of patients is to find out what is the matter; that is, to fix the diagnosis. This does not consist merely in giving a name to the main disease sup- posed to be present, but includes a knowledge of all functional or organic alterations. The physician should endeavor to perfect him- self in this from the beginning and should by no means wait until all the data are at hand before making a written diagnosis. A. The admitting physician should begin by making as complete a diagnosis as his examination permits. This should indicate the reason why a patient is admitted to a particular service. If there are suspected complications, as an acute abdominal infection, a con- sultation with the other service concerned should be had before as- signing a patient to a service. If this is not possible, the best judg- ment should be followed. B. If the patient is seen immediately by a member of the house staff, the latter should make an effort to confirm the admission diag- nosis or to make a better one. C. Diagnoses from Anamnesis.-The person who takes the history (graduate or undergraduate) should write at the end of the history a diagnosis per anamnesis or a series of diagnoses based on the his- tory. ? diagnoses or multiple ??? diagnoses can be used. Those who work after the anamnesis should comment on such diagnoses by adding 0. K. or V or ! or ? or at greater length in a note giving signature after any change. D. Diagnoses after the Physical Examination should check up the first diagnoses adding to or altering them as seem indicated. After the physical examination, with or without some of the laboratory examinations, as full a diagnosis as possible should be written over the examiner's signature. This also should be checked up by those who go over the patient later. After completion of laboratory work all differential diagnostic findings are added in notes, as urine negative if normal; findings in brief, if abnormal; P. S. P. and concentration diuresis function; blood negative, if normal, but with findings in brief, if abnormal; chemical, serological and bacteriological results; sputum, stomach contents, stools, or any other findings of significance. All results of examinations which give diagnostic information, such HISTORY TAKING AND PHYSICAL EXAMINATION 63 as blood cultures, serum reactions, etc., should be entered as new diagnoses. These as well as the accepted diagnosis should be entered on the front page as early as possible. In careful effort at complete diagnosis, indicate primary diagnosis and diagnoses of all organs and functions affected. Note also all spared organs which might have been involved, i. e., "arteriosclerosis, general, with kidneys clinically negative." The primary diagnosis is the chief or most important affection incapacitating the patient or causing his death. Subsidiary diagnoses follow in the order of importance. The main associated disease condition is to be indicated. International nomenclature and classification are to be used. Notes as to the progress of the diagnostic studies and the results of treatment are to be made at least bi-weekly by the interne. Criti- cally ill patients are to have, more frequent notes and when definite changes take place in the patient's condition, a note should be made by the interne. It is believed that an interesting study can be followed from care- ful attention to the above rules and comparison can be made from the value of diagnoses by the history and first examination and the final complete examination. Abbreviated Histories All routine histories and physical examinations are to be full and complete. If for any reason it is impossible to get complete data, as in the case of foreigners for whom no interpreters can be found, or in the case of comatose patients brought in by attendants unac- quainted with the happenings, a note as to the reason for the absence of a history is to be made. Every effort must be made to obtain as much data as possible from the patient's family, friends, or those accompanying the patient to the hospital. In critically ill patients, it is often advisable not to disturb the patient any more than is absolutely necessary. Judgment is to be used here and the patient spared unessential physical examination, as well as questioning. All possible data from other sources are to be secured. After the crisis, as the patient improves, the required records are to be obtained. Every patient admitted to the service must have the routine ward work carried out and recorded. 64 METHODS IN MEDICINE In case of patients admitted for special studies or treatment, as those sent in for lumbar puncture or arsphenamine injections, radium or x-ray treatment, metabolism or blood studies, a routine history and physical examination must be obtained on the first admission of the patient to the hospital. On subsequent admissions the front page must be filled out com- pletely, including the diagnoses of the previous history. The object of the admission is stated with a note as to the course of events since the patient left the hospital. Also a comparison of the symptoms and signs present with those recorded on the previous admission. A note as to the psychic and general condition, the condition of the kidneys, blood pressure, heart, lungs, and alimentary canal; pupils, knee jerks, Achilles reflexes, presence or absence of Romberg- ism or any neurological or physical findings noted as pathological on any previous admission. With any alteration in signs or any symp- toms, more detailed examinations are indicated. Special Case Histories Rules Concerning Abstracts for the Department of Pathology On medical cases that have come to autopsy, the following sug- gestions are made in order to provide uniformity in abstracts for the Department of Pathology. Before each autopsy is begun the complete clinical diagnosis should be written in the history and placed on the blackboard in the post- mortem room. In abstracts give full name, age, sex, medical number, dates of admission and death. Chief complaint. Pertinent facts in the previous history. Present illness and symptoms. Complete chronological account, especially any facts related to the suspected pathological anatomy. Physical examination. Brief but comprehensive statement of physi- cal findings, including laboratory data. Diagnosis in full. Treatment in outline. Course in hospital. Any new symptoms or findings developing before exitus. Any comments thought necessary or desirable. Blackboard diagnosis. CHAPTER IX LABORATORY NOTES, SUGGESTIONS, AND RULES 1. All findings in the laboratory or on the wards must be reported to the house officers for confirmation at the earliest possible moment. All unusual findings should be reported to the chief and others of staff, with specimens. No unusual finding should be lost, or its sig- nificance left undetermined. In case of any unusual laboratory findings, make a detailed note in the body of the history. Sketch all notable pathologic cells, para- sites, ova, etc. 2. Smears with findings of importance in the diagnosis should be stained and, if made on cover glasses, should be mounted with the smear side down. All immersion oil should be removed with xylol; the slide dried, labeled and turned in to the interne. Miscellaneous Suggestions The Wassermann tests are done on Tuesdays and Fridays. Speci- mens to be examined on these days must be in the laboratory on the afternoon preceding. Blood specimens should be taken promptly on all new admissions. Blood specimens are to be collected in Wassermann tubes; the tubes slanted until a coagulum forms and then promptly delivered to the Wassermann laboratory. The needles used in securing blood for Wassermanns, etc., are to be cleaned by the student, sharpened and returned to the head nurse on the ward. Requests for Wassermanns and any clinical pathologic or labora- tory examinations are to be filled out with complete data and dated. All such slips are to be signed with the resident's name and not the interne's or the student's. Any special procedure done, as the taking of blood for Wasser- mann, blood chemistry as an N. P. N. or the doing of the P. S. P., gastric analysis, etc., or any therapeutic procedure as intramuscular 65 66 METHODS IN MEDICINE mercury injection or intravenous foreign protein injection must be reported to the head nurse for recording on the graphic T. P. R. chart. General Rules All specimens for examination will be placed in the ice box. When through examining, place vessels on the shelf below the sink. If it is desired to keep a specimen, place it in the ice box, properly labeled. All specimens left on the desks or tables, labeled or unlabeled, will be thrown out. When through using, all glass-ware should be cleaned, emptied, washed, rinsed with tap water, and returned to its proper place. Glass slides should be washed and placed in a glass jar provided for them. Do not use graduated or volumetric pipettes for removing sediment from urine specimens, etc. Plain pipettes are provided for that pur- pose. Do not use round filter paper for drying slides; use blotting squares provided for this. Reagent bottles should be returned to their proper places on the shelf and not left standing unstoppered where used. Remember how to remove a stopper from a bottle and hold it. Do not try to run the centrifuge at more than first speed. Throw all waste into jars provided for that purpose. Make a personal effort to keep the laboratory in as good condition as possible, both clean and well stocked. Articles needed and not found should be noted on the want list, when they will be provided as soon as possible. Turn off gas and electric lights when through using. No smoking or unnecessary noises will be tolerated. Scratch pads are furnished for notes and calculations. Do not use filter paper for such purposes. Record all findings promptly on the Barnes Hospital history lab- oratory forms and attach your signature (name in full, not initials). CHAPTER X LABORATORY ROUTINES AND METHODS 1. Routine Sputum Examination Admission specimen on all cases raising any. Daily first morning specimen in all cases of suspected tuberculosis until at least 5 negatives have been obtained on consecutive days. Verify all "positives" once and demonstrate specimen to the resident physician. 1. Amount, (approximate). 2. Character (a) Consistency, viscidity, mucoid, muco-purulent, purulent, serous, nummular or layered. (b) Odor. (c) Color. (d) Blood, especially note whether blood is streaked or inti- mately mixed. 3. Fresh sputum examination on glass plates for bronchial casts, elastic tissue, "heart failure" cells, dust cells, eosinophiles, crystals, spirals, pearls, plugs, parasites, and ova. 4. Stained sputum examination for: (a) Tubercle bacilli by acid-fast stain (Ziehl Neelsen). (b) Cocci by Gram's stain or Loeffler's stain. (c) Influenza bacilli by weak carbol fuchsin or safranin counterstain with Gram's method. Use tooth-picks in picking out specimens. Select small cheesy or white glistening particles for staining. Routine Methods of Sputum Study All suspicious particles or lumps should be treated with 1 per cent sodium hydroxide, pressed out between cover-slip and slide and examined microscopically. Leptothrix buccalis which may resemble elastic tissue may be 67 68 METHODS IN MEDICINE differentiated by its characteristic violaceous color when stained with Gram's iodine. Concentration of Elastic Tissue.-Boil 10 c.c. of sputum with an equal volume of 10 per cent sodium hydroxide until the solution is homogenous. Cool, dilute with water and centrifugalize. Ex- amine the sediment pressed out on a glass slide beneath a cover glass. Concentration of Organisms.-Mix thoroughly 10 c.c. of sputum with an equal volume of Antiformin, a proprietary preparation made up of equal parts of 115 per cent of caustic soda and 20 per cent sodium hypochlorite. Digest the foaming mixture for 6 to 12 hours in a sedimentation glass. The organisms, which remain uninjured, are concentrated in the sediment. This then can be stained, injected intraperitoneally in a guinea pig or cultured. Ziehl-Neelsen Technic for Staining Tubercle Bacilli A smear preferably of a caseous particle is air dried, fixed by passing the slide film side up through a Bunsen burner flame slowly for 10 times. The slide is covered with Ziehl-Neelsen's (4.5 per cent phenol 3 per cent basic fuchsin) stain. Keep the solution steaming for three minutes. Wash off the excess stain with water and decolorize preferably in acid alcohol (3 c.c. concentrated IIC1 in 97 c.c. 70 per cent alcohol) until all the thin portions of the film have lost all the red color and are of a lavender tint. Counter- stain by applying Loeffler's alkaline methylene blue for a few sec- onds. Wash off in water, dry the preparation and search for the acid-fast staining organisms, with the oil immersion lens. Do not search any one preparation for more than fifteen minutes. Gram's Stain.-Cover the heat fixed smear with Sterling's stain (2 per cent anilin oil 10 per cent alcoholic 5 per cent gentian violet) and allow to stand for 1 minute (the ordinary anilin oil gentian violet requires five minutes). Pour off the excess of stain and cover the preparation with Gram's solution (.33 per cent iodine .66 per cent potassium iodide solution, same as Lugol's) for two to three minutes. Pour off the excess mordant and decolorize in 96 per cent alcohol until no further stain can be washed out. This takes one-half to two minutes. Counterstain the grayish film with 10 per cent safranin, dilute carbol fuchsin or Bismark brown. LABORATORY ROUTINE 69 2. Routine Examination of Stomach Contents In all cases with gastrointestinal symptoms or a severe anemia, a gastric fractional analysis is to be done and repeated as soon as pos- sible if abnormal. Record results on standard graphic gastric charts. All vomitus is to be thoroughly examined and all pathologic findings noted. 1. Vomitus, or test meal used, and method used as Rehfuss' or Gorham's. 2. Time in stomach. 3. Amounts recovered. 4. Character. (a) Odor. (b) Color. (c) Consistency. (d) Food remains, mucus, bile, blood, Boas' reagent, tissue fragments or any unusual findings. 5. Chemical. (a) Presence of free HC1 by Gunzberg's test and Congo red paper, Boas' or Tbpfer's reagent. (b) Amount of free HC1 by titration, using Tbpfer's reagent. (c) Estimation of total acidity by titration using phenol- phthalein and N/10 NaOH. (d) Presence of lactic acid by Uffelmann's, Kelling's or Strauss' test. (e) Presence of blood by guaiac or benzidin, or microscopic examinations. 6. Microscopic examination for Oppler-Boas bacilli, sarcinac, moulds, yeasts, and unusual cells. Routine Methods of Gastric Analysis Qualitative Tests for Free Hydrochloric Acid Beas' Method.-Mix in a porcelain dish a few drops of gastric juice and Boas' reagent (5 gm. resublimed resorcinol and 3' gm. cane sugar in 100 c.c. of alcohol). Warm the porcelain dish care- fully over a flame, evaporating the mixture to dryness. A rose-red color which fades on cooling indicates the presence of free hydro- chloric acid, a dirty brown, an achlorhydria. 70 METHODS IN MEDICINE Gunzburg's Test is performed in the same way as the above and gives exactly similar results and even a sharper reaction. The Gunzburg reagent (2 gm. phloroglucin, 1 gm. vanillin in 30 c.c. of absolute alcohol) is however unstable. Quantitative Tests for Amount of Free HC1 and Degree of Total Acidity Measure in a volumetric pipette 10 c.c. of filtered gastric juice, dilute with 20 c.c. of distilled water, add 2 to 4 drops of Topfers indicator (0.5 per cent alcoholic solution of dimethylamidoazo- benzol). In the absence of free hydrochloric acid the color of the solutions is yellow while in the presence of free HC1 a red color promptly appears. Tenth normal sodium hydroxide is then slowly added from a burette until the red color entirely disappears and the solution is of a canary yellow color. The number of c.c. of the alkali are read off the burette and the amount of free HC1 present in 100 c.c. is calculated. One c.c. of the decinormal sodium hy- droxide being equivalent to one c.c. of the decinormal free HC1. The figure remains the same and the number of c.c. of decinormal NaOH necessary and consequently of decinormal HC1 present, is reported as the degree or the acidity per cent. This figure multi- plied by .00365 gives the free HC1 content in grams. After the end point with the dimethylamidoazobenzol is obtained as above, 2 to 4 drops of 1 per cent alcoholic solution of phenol- phthalein are added and the titration resumed. The decinormal sodium hydroxide is added from the burette until a rose-red color appears which is not intensified by the further addition of alkali. At this point all the acids present have been neutralized. The num- ber of c.c. of decinormal NaOH used for the entire titration equals the number of c.c. of decinormal acid present and this multiplied by 10 gives the number of c.c. per 100 c.c. of fluid and is reported as the total degree of acidity or the acidity per cent. Note: Dimethylamidoazobenzol reacts best to the presence of highly ionized acids (Ph 3' to 4) and is consequently used to indi- cate the approximate concentration of the strong mineral acid. The acid protein salts and organic acids do not dissociate with the production of enough hydrogen ion to cause color changes with the above indicator and therefore titration with phenolphthalein, which LABORATORY ROUTINE 71 shows color changes in weakly alkaline solution (PH 8 to 9) is carried out to indicate approximately the total acidity concen- tration. Lactic Acid Tests Uffelmann's Test.-The reagent, which must always be freshly prepared, consists of 20 c.c. of 1 per cent phenol solution, 1 drop of 10 per cent ferric chloride solution and distilled water sufficient to make the amethyst-blue solution transparent. A few drops of filtered gastric contents, or preferably of a watery solution of the residue of an ethereal extract of the gastric contents, are added to the reagent. A change in color in the reagent to a canary or lemon yellow is a positive reaction. The test is not specific. Kelling's Test.-The reagent which likewise must be freshly pre- pared, consists of 2'0 c.c. of distilled water to which 1 drop of 10 per cent ferric chloride has been added. The reagent is divided into two parts, to one of which a few drops of the filtered gastric contents or preferably the extract of the same are added. The ap- pearance of a canary or lemon yellow color is the positive reaction. Strauss' Test.-This method requires the Strauss' separatory fun- nel. Into this funnel are introduced 1 c.c. of filtered acidified gas- tric contents, then 20 c.c. of C.P. ether are added, and the mixture thoroughly extracted by shaking. Decant and allow the gastric fluid, the lower 5 c.c., to run off through the stopcock. Make up the volume with distilled water and add 2 drops of a 1 per cent solution of ferric chloride. The presence of any abnormal amounts, 0.1 per cent or more, of lactic acid will give a definite greenish yellow. Tests for Bile and Blood.-These are performed according to the technics outlined for these substances under the Routine Tests for Urinalysis. 3. Routine Stool Examinations Admission specimen on every case and one each week thereafter. Every specimen or at least one daily in all gastrointestinal, sus- pected parasite cases, or severe anemias. Record always: 72 METHODS IN MEDICINE 1. Amount (approximate). 2. Character: (a) Form. Formed, unformed, scyballous, cylindrical, rib- bon or tape-like. (b) Color. Light or dark brown, black or tarry, clay colored or acholic, green. (c) Consistency. Soft or firm, uniform or mixed, frothing or yeasty. (d) Odor. Indol, skatol, or rancid, butyric acid. (e) Undigested food, mucus, blood, parasites, foreign bodies. 3. Test for blood by guaiac or benzidin. 4. Test for bile, hydrobilirubin or bilirubin. 5. Microscopic. (a) Undigested food, meat fibers, starch, cellulose, vegetable cells, fat. (b) Mucus. (c) Blood. (d) Pus. (e) Crystals. 6. Parasites or ova. Warm stools. Cultural and concentration methods. Routine Methods Study of Feces Tests for Occult Blood.- The Guaiac Test.-About 10 grams or c.c. of fat free or other extracted feces are ground thoroughly in a mortar with 2.5 c.c. of glacial acetic acid added. The mixture is extracted with 10 c.c. of ether. This ethereal extract can be subjected to spectro- scopic as well as chemical tests. Overlay 5 c.c. of a freshly prepared 2 per cent or at the most 4 per cent alcoholic tincture of guaiac and 2.5 c.c. of fresh 3 per cent hydrogen peroxide or ozonized turpentine with the ethereal extract. A blue ring at the zone of contact is a positive reaction. The Benzidine Test.-The test may be done exactly as the above except for the use of a saturated alcoholic solution of benzidine instead of the guaiac. A green color is a positive reaction. The modified benzidine test of Roberts (Jour. Am. Med. Soc., Ixv, p, 244, 1915) is a very practical procedure. This consists in a stable LABORATORY ROUTINE 73 5-grain tablet titrate composed of 1 part of benzidine to 20 parts of sodium perborate, triturated with great care. The moderately friable tablet is placed in a white porcelain dish and partially im- mersed in the weak emulsion of stool, stomach contents or urine sedi- ment to be examined. A drop of glacial acetic acid added to the moistened tablet gives rise, in the presence of blood, to a more or less promptly appearing greenish blue color. The tablets may be secured from E. R. Squibb & Sons, New York. The Spectroscopic Examination with a direct vision spectroscope is the most accurate test. The ethereal extract of acidulated feces gives in positive cases the acid hematin band in the red. To rule out the chlorophyl band which is near this in the red, treat the ether extract with sodium hydrate alcohol and ammonium sulphide, and in the presence of blood derivatives, get the characteristic two band spectrum of haemochromogen, which chlorophyl does not yield. Test for Hydrobilirubin and Bilirubin Schmidt's Test.-Grind up about 10 grams of feces with about 10 c.c. of a saturated solution of bichloride of mercury and allow the mixture to stand 2 to 2'4 hours. The development of a red color in the particles indicates the presence of a hydrobilirubin bi- chloride compound, while a green color indicates that bilirubin has been present and has been oxidized to biliverdin. The reaction may be slow and is not to be considered negative until at least 18 hours after the addition of the mercury bichloride. Microscopic Reactions Applied to Feces For microscopical study, usually four drops of a weak emulsion of the stool are placed at intervals on a glass slide. To the first drop unadulterated or mixed with stain or chemical as 2 per cent acetic acid for clearing, a cover slip is applied. This is examined under the low power for cellular element. A drop of Lugol's solution is added to the second drop of feces and the cover slip is applied. Starch granules will be stained a deep blue with this reagent. A drop of a saturated 0.2 per cent alcoholic solution of Sudan Ill is added to the third drop of stool suspension. This is for the 74 METHODS IN MEDICINE microchemical study of the amounts and proportions of the types of fats. Sudan III stains neutral fat droplets an orange red to a blood red; fatty acid crystals, which are delicate, curved, needle- like crystals in masses, a distinct orange red; while soaps are un- stained, long, needle-like or short, plump crystals in fan-like clus- ters or flat plates. The fourth drop of stool emulsion is treated with a 5 per cent alcoholic carbol-fuchsin. With this reagent neutral fats do not stain; fatty acids stain a brilliant red; while soaps stain a dull red. 4. Routine Urine Examination Routine as to Specimens.- (a) Complete examination of admission and first 24-hour specimen. Quantitative estimation of albumin and sugar if any is present. (b) One 24-hour specimen for all patients every seven days. (c) Catlieterized specimen in cases where there is any question of genito-urinary infection other than gonorrhea but especially in women showing leucocytes or epithelial cells in excess. (d) Cystitis and pyelitis cases, fresh specimen to laboratory daily. Examination as indicated. (e) Nephritis and cardiac failure cases, 12-hour speci- mens to laboratory daily. Day and night 12-hour amounts, specific gravity, quantitative albumin and chlorides and reaction recorded daily on special cardio- renal chart with all other available data. Complete examinations weekly. In acute nephritis, complete daily. (f) Diabetes cases, amount daily with complete examination especially quantitative sugar and diacetic acid and acetone tests. Record according to standard chart with all data available. (g) In leukemia and bone marrow diseases, especially under x-ray treatment, a daily test for Bence-Jones protein. (h) Hourly specimens for 3' hours for sugar, and quantitative 24-hour specimen examination if any is found, after sugar tolerance test or adrenalin test. (i) Complete examination of a fresh specimen in every case before arsphenamine injection. LABORATORY ROUTINE 75 Phenolsulphonephtlialein tests are to be done on admission and repeated after a week or sooner if indicated. Routine as to Examination of Urine 1. Amount. Only if a 12 or 24-hour specimen, otherwise note if specimen is fresh or mixed. If a 12-hour specimen, note whether day or night output and record as D. or N. and not a. m. or p. m. 2. Character. (a) Color. (b) Clear, turbid, or opalescent. (c) Sediment granular, flocculent and color. (d) Floaters. 3. Specific gravity. 4. Reaction to litmus paper. 5. Sugar. First examination use Fehling's, Benedict's, and Ny- lander's reagents. Subsequently one or two as seems necessary. If sugar is present, do a quantitative estimation and test for diacetic acid and acetone. 6. Albumin. Always have clear urine, filtering, or even treating with infusorial earth and filtering when necessary. First exami- nation use two tests, either heat and acetic, heat and nitric, or acetic acid and potassium ferrocyanide tests. If the cloud is recognizable only against a black background, record as a "very slight trace" (V. S. T.). If the cloud is recognizable without a black background, and under 0.25 gm. per liter, record as ''trace" (T.). Any amount over a trace should be measured with the Esbach tube and Tsuchiya's reagent. 7. Special tests of first examination. (a) Diacetic acid by Ferric chloride test. (b) Acetone by Nitroprusside test. (c) Bile by Foam and fuming and Nitric Acid test. (d) Urobilinogen by Dimethylamidobenzaldehyde. (e) Urobilin by Zinc Acetate Fluorescence. (f) Blood by Guaiac test or Benzidine test. 8. Sediment. It is highly important that the sediment should be examined from fresh urine. If the urine is alkaline, or has been 76 METHODS IN MEDICINE standing any length of time, it is better to get a fresh specimen. Measure and record the amount of sediment in definite figures as millimeters in the tip of standard centrifuge tubes. Always use centrifugalized specimens. Withdraw the total sedi- ment from the tube with the regular broad pointed glass pipette for urine sediment. Wipe off the pipette with a dry towel and examine small individual drops of the whole sediment on the regular 3.5 x 4.5 cm. glass plates. Note normal findings, then leucocytes, epithelial, squamous and round, and red blood cells, stating number per high or low power field. Casts, variety, number, and sizes. Unusual crystals. Ova. Stains of sediment-smears fixed with albumin in cases with pus cells and organisms present in catheterized specimens. Routine Methods of Urine Study Qualitative Tests for Albumin.- Nitric Acid Test.-Heller's ring, a white cloud at the zone of contact, appears in urine containing albumin when the latter is layered over concentrated nitric acid at room temperature. The test is usually made by lowering a pipette containing a column of urine into a test tube containing concentrated nitric acid. The heavy acid will rise in the pipette carrying the column of urine above it. A better zone of contact may be made by overlaying nitric acid with urine from a pipette, or pipetting nitric acid beneath a volume of urine in a test tube or a small wine glass. With the wine glass technic approximate amounts of albumin may be estimated, as follows: (Ogden.) S.P.T. The slightest possible trace or amount detectable as a hazy ring under the most favorable conditions with a black back- ground and light from the side. S. A slight trace when the ring can be seen without a back- ground or special light and from above, with the bottom of the glass remaining perfectly distinct. T. A trace when the ring is distinct, clear, quite dense but not opaque from above, and not flocculent. This roughly equals 0.1 per cent. L.T. A large trace when the ring is so dense that the bottom of LABORATORY ROUTINE 77 the glass cannot be seen, but a faint ray of light is transmitted. This is roughly 0.15 per cent. L.A. A large amount when the ring is absolutely opaque from above and very flocculent from the side. This is approximately 0.25 per cent. Heat and Acetic Acid Test.-Boil the upper few c.c. of clear urine in a test tube that is half full of filtered urine. Add five drops of 2 per cent acetic acid. A persisting turbidity or precipitate indi- cates albumin, generally, but occasionally it may be due to the presence of nucleoalbumin or mucin. Acetic Acid and Potassium Ferrocyanid Test.-To 5 c.c. of clear urine add an equal volume of 8 per cent acetic acid. A turbidity occurring in this mixture, the result of the presence of nucleo- albumin or mucin should be removed by filtration. The clear acid-urine mixture is divided into two approximately equal parts in clean test tubes. To one of these volumes add not more than 5 drops of 5 per cent potassium ferrocyanid solution, observing the reac- tion of each drop against a black background and with light from the side, comparing the tested solution with the control. Any tur- bidity is a positive reaction. Differentiation of Substances Giving Suggestively Positive Albumin Reactions Hetero-Proteose or Bence-Jones' Body can be differentiated by the characteristic reactions as follows: On slowly heating in a water- bath a urine containing the rare protein, a cloudiness even as low as 40° C. appears. This increases as the temperature rises and a flocculent precipitate is noted between 60° C. and 70° C. On boil- ing, the precipitate dissolves, to reappear again as the solution cools. Complete precipitation is obtained by the addition of two volumes of 95 per cent alcohol, of ammonium sulphate, or of sodium chloride if the urine is acidulated with acetic acid. Saturated magnesium sulphate and strong acetic acid give no precipitate. The precipitates with nitric acid and the acetic acid-potassium ferrocyanid mixture dissolve on boiling and reappear on cooling, while the precipitate with picric acid does not dissolve on boiling. Nucleoalbumin and Mucin give the ring a centimeter above the zone of contact in the nitric acid test. The substances can be pre- 78 METHODS IN MEDICINE vented from precipitating in the heat and acetic acid test by the addition of a half volume of a saturated solution of sodium chloride. Mucin is precipitated by dilute phosphoric acid and is soluble in excess of acetic acid. It contains no phosphorus, but a gluco- samine which can be split off by heating with dilute acids and tested for with Fehling's solution, which it reduces. Nucleoalbumin is not precipitated by dilute phosphoric acid and is not soluble in excess of acetic acid. It contains phosphorus, but no carbohydrate group. Phosphates, urates, uric acid, urea, and bile acids are only con- fusing in concentrated urines and this can be prevented by diluting the specimen with an equal volume of distilled water. Phosphates often appear on heating and disappear as soon as acetic acid is added. Urates disappear on heating. Resins which may be present in cases receiving genito-urinary antiseptics may be precipitated by hydrochloric acid or removed by benzol. Quantitative Methods for Albumin Estimation Esbach's Method.-Fill an Esbach tube to the level 17 with fil- tered (and when necessary diluted) acid urine of a specific gravity preferably not over 1.008, and an albumin content of not over 3 grams per liter. Add Esbach's reagent (Picric acid 10 gms., citric acid 20 gm., distilled water 1000 c.c.) to the level R. Mix slowly, inverting carefully, avoiding foaming. Keep in a cool place at 15° C. constantly for 24 hours and read results in grams per liter. Kwilecki's Modification is a rapid clinical method of moderate accuracy similar to the above. It consists in adding 10 drops of 10 per cent ferric chloride to the urine before adding Esbach's reagent. Then warm the tube and contents in a water-bath and keep at 72° C. for five minutes and read. Tsuchiya's Method is done in the way described for the Esbach method but is more accurate, due to the use of Tsuchiya's re- agent (phosphotungstic acid 1.5 gm., 96 per cent alcohol 9.5 c.c., and concentrated hydrochloric acid 5 c.c.) as the precipitating agent. For accurate metabolic work the gravimetric method is prefer- able ; for clinical work, however, the above suffice. LABORATORY ROUTINE 79 Qualitative Tests for Glucose Fehling's Test.-Equal parts (about 2.5 c.c. each) of Fehling's No. 1 Blue (or copper sulphate solution) and Fehling's No. 2 White (or alkaline tartrate solution) are mixed and diluted with an equal volume of water and boiled. To this boiling mixture % c.c. or 8 gtt. of "urine is added and the solution removed from the flame and allowed to cool. A yellow or red precipitate is a positive reaction. Benedict's Test.-To 5 c.c. of Benedict's qualitative solution add an equal volume of distilled water and % c.c. of the urine to be tested. Boil the mixture for two and a half minutes in a free flame, or for five minutes in a water-bath. Allow to cool. The ap- pearance of a red, yellow, or greenish color throughout the solu- tion is a positive reaction. This test is more delicate than Feh- ling's. Fermentation Test.--The closed arm of the fermentation tube or sac- charimeter is filled with diluted fresh urine from a 10 c.c. volume in which a half c.c. of fresh yeast cake has been carefully but thoroughly mixed just before the filling. A normal urine, and a normal urine to which 1 per cent sugar has been added are treated in a similar way as controls. The three tubes are then incubated for 18 or 24 hours. The amount of evolved gas collected in the closed arm is measured and tested as to its make-up. CO2 is ab- sorbed by KOH. The amount of CO2 evolved is an index of the amount of sugar that was present. This can also be estimated by the amount of reduction of the specific gravity during the fermen- tation. The reducing substances can be differentiated, as follows: Fermentation is positive in the case of glucose, levulose, and maltose. It is negative in the case of lactose, galactose, pentoses, glucoronates, and glucoronic acid. Phenylhydrazine hydrochloride produces microscopically charac- teristic osazones with maltose and lactose directly. Glucose, levu- lose, mannose, and glucosamine all give the same type of osazone. Solutions yielding crystals that melt at about 200° C. when fer- mentable contain glucose if there is dextrarotation, and levulose if there is levarotation; when not fermentable the solution origin- ally contained lactose. Solutions yielding crystals that melt at about 150 ° C. contain 80 METHODS IN MEDICINE pentoses when the reaction to Bial's Orcinol test is positive, and isomaltose when the latter test is negative. Five c.c. of Bial's Reagent (100 c.c. of 30 per cent hydrochloric acid, 0.2 gm. of orcin, and 5 drops of 10 per cent ferric chlorid sol.) are boiled, removed from the flame and the unknown urine added drop by drop not to ex- ceed a total of 1 c.c. of urine. A green color, which appears promptly, is a positive reaction. Glucuronates and glucoronic acid yield osazones only after the solution containing them has been warmed with dilute sulphuric acid. These also give a positive violet to blue color with Tollen's reagent, % c.c. (1 per cent solution of naphthoresorcin) added to 5 c.c. of urine and an equal volume of concentrated HC1 and boiled. Borchardt's Reagent (25 per cent hydrochloric acid and a few crystals of resorcinol). Boiled with an equal volume of urine for 30 seconds gives a red color, which after cooling and alkalinizing and shaking with acetic ether yields a yellow ether in the presence of levulose, provided indican is removed by Obermayer's extrac- tion if any is present, and provided that anthracene purgatives have not been taken. Quantitative Methods for Glucose Estimation Benedict's Quantitative Method.-The urine is well diluted un- less the sugar content is low. Fifty c.c. of diluted urine are placed in a burette which is clamped high on the ring stand. Twenty-five c.c. of Benedict's quantitative sol., the reduction of which requires the equivalent of 50 mg. of sugar, are placed in an Erlenmeyer flask, diluted with an equal volume of water and 5 gm. of anhydrous sodium carbonate added, and the mixture heated to boiling. The urine from the burette is then run in rather rapidly in 1 c.c. amounts, allowing a few seconds for boil- ing between spurts, until a chalk-white precipitate appears and the blue of the reagent has disappeared. Each result should be checked by a repetition of the titration. The amount of urine used multiplied by the dilution equals the amount of urine containing 50 mg. of sugar (the Benedict equiv- alent). From this can be calculated the amounts of sugar in 1 c.c., 100 c.c., and the 24-hour urine volume. LABORATORY ROUTINE 81 Other Qualitative Tests Applied to the Urine Routinely Diacetic Acid Tests.- Gerhardt's Test (modified).-To 10 c.c. of freshly passed urine add 10 per cent ferric chloride drop by drop until a precipitate of phosphates no longer forms; the phosphates are filtered off and a few more drops of the reagent are added to the filtrate. A Bor- deaux-red color which fades on boiling the solution is a positive reaction. The substances which give the red reaction in the urine of patients to whom drugs have been administered usually cause intensification or darkening of the red to a violet-blue or black on boiling. The test is thus not specific. Arnold's Test (modified.)-One volume (5 c.c.) of solution A (1 gm. of para-amidoacetophenon, 2 c.c. concentrated hydrochlo- ric acid, and 100 c.c. distilled water) and a half volume (2.5 c.c.) of solution B (1 per cent sodium nitrite) are mixed and added to an equal total volume (7.5 c.c.) of urine to which one drop of strong ammonium hydroxide has been added. On shaking, the mixture becomes brick-red in color. One-half c.c. to 2 c.c. of this mixture, depending on the probable amount of diacetic acid that is present, are added to 15 c.c. to 20 c.c. of concentrated hydro- chloric acid to which 2 to 4 drops of 10 per cent ferric chloride and 2.5 to 5 c.c. of chloroform have been added. The test tube is stoppered and gently shaken for a minute. A violet coloration in the chloroform is the characteristic reaction of diacetic acid, in the absence of which the chloroform is red or yellow. Acetone Tests Lange-Le Nobel-Legal (Nitroprusside) Test.-To 5 c.c. of urine add 1 c.c. of glacial acetic acid and one small crystal of sodium nitroprusside. Shake until the latter crystal is completely dis- solved. The use of two drops of a dilute 2 per cent freshly pre- pared sodium nitroprusside solution instead of the crystal would obviate the shaking. Overlay the mixture with 2 c.c. of strong ammonium hydroxide. A purplish-red ring at the zone of contact is a positive reaction. Gunning' Lieben Iodoform Test.-Alkalinize 5 c.c. of urine dis- tillate with concentrated sodium hydroxide and add at the most % c.c. of tincture of iodine. Treat the mixture with concentrated 82 METHODS IN MEDICINE ammonium hydroxide until the black nitrogen iodid precipitates. This black precipitate disappears within 18 to 24 hours, leaving, when the reaction is positive, a yellow sediment of characteris- tic odor and microscopically characteristic hexagonal iodoform crystals. Tests for Urinary Pigments.- Bile Tests.- Foam Test.-A greenish-yellow, greenish-brown, yellowish- brown, mahogany-brown, or dark green colored bile-containing urine, when shaken shows a colored foam either yellowish-brown or greenish, while the foam of normal urine is colorless. Nitric Acid Test (Gmelin's or Bosenbach's Method).-Urine acid- ulated with hydrochloric acid is layered over concentrated nitric acid. A green ring with or without a play of colors through blue, violet, and red to yellow is characteristic. If a quantity of urine treated with milk of lime is filtered and a drop of fuming nitric acid is dropped in the apex of the filter paper cone, a green re- action or a play of colors is characteristic in the presence of bile pigment. Urobilinogen Test.-Ehrlich's reagent (4 per cent dimethylamido- benzaldehyde in 50 per cent HC1) is added drop by drop to freshly voided, cooled urine that has been acidulated by two drops of HC1 to a 10 c.c. volume. The formation of a red color in the cold indi- cates an excess of pigment. The nonappearance of the color even after heating signifies an absence of the chromogen. Urobilin Test.-Schlesinger's reagent (1 per cent alcoholic sol. of zinc acetate) is added in equal volume to the unknown urine. The intensity of the fluorescence is an index of the amount of urobilin present. A saturated absolute alcoholic sol. of zinc acetate may be used as the reagent. Better results are usually obtained by extracting 50 c.c. volumes of urine with chloroform, ether, or amyl alcohol. When quantitative results are desired the urine should be treated with Lugol's sol. to change all urobilinogen to urobilin. The quan- tity is roughly estimated by the number of dilutions of the fluores- cent sol. necessary to remove the spectral lines. LABORATORY ROUTINE 83 Guaiac Test.-Equal parts of a fresh 1 per cent alcoholic tinc- ture of fresh guaiac and ozonized turpentine or fresh hydrogen peroxide, 5 c.c. of urine that has been boiled and cooled and acid- ified, are layered, with the guaiac oxidizer solution above. A bluish- green to a brilliant blue ring is a positive reaction. When the reac- tion is doubtful the urine should be strongly acidulated with acetic acid and extracted with ether and the reaction tested for with the ethereal extract. Benzidine Test.-The technic is similar to that for the guaiac test. Instead of guaiac sol., a fresh saturated alcoholic sol. of benzidine is used. A delicate green color is positive. This test is so delicate that the diet must be meat-free if any significance is to be at- tached to a positive reaction. Blood Pigment Chemical Tests 5. Routine Blood Examination Routine as to Specimens.- On admission: (a) Red and white blood cell count. (b) Hemoglobin estimation. Tallquist Scale may be used routinely, with Sahli hemometer estimations in every case showing 70 per cent or below or over 100 per cent by the Tallquist. (State method used). Color index. (c) Repeat hemoglobin estimation once per week. (d) Repeat Rbc. count within a week if hemoglobin is below 70 per cent or over 100 per cent. (e) Repeat all Wbc. counts within 3 days and once per week. If Wbc. is over 15,000, repeat daily. (f) Daily Wbc. counts in typhoid fever or pneumonia cases dur- ing the febrile period and more often if indicated. (g) On all primary and severe secondary anemias and all leu- cemias, complete blood examination biweekly with standard graphic blood charts. (h) Intravital staining for reticulated cells once each week to estimate regeneration. (i) When there are rapid alterations in the blood picture, exami- nations should be made oftener as per directions. 84 METHODS IN MEDICINE Routine as to Examination of Blood 1. Fresh Blood.- (a) Color and consistency of each drop as it comes out. (b) Rouleaux formation and marked differences in clotting and degree of flow. (c) White blood cells, approximate number, unusual pictures as leucocytosis, lymphocytosis, eosinophilia, myelocytes and pigmented cells. (d) Red blood cells, shape, color, size, nucleated cells, re- ticulated cells. (e) Parasites. 2. Routine Stains to be used are Wright's, Wilson's, or Jenner's. Ehrlich's triacid and peroxidase stains when indicated. Stained smears made on glass slides or on cover slips and mounted blood-side- down upon glass slides. Mount covers in cedar oil only. Balsam fades them. (a) Note all characters looked for in fresh blood. (b) Also make a differential count of at least 200 cells, re- cording the actual number of cells counted of each variety, the percentage, and the absolute number per c.mm. estimated from the leucocyte count made at the time of the differential. (c) Include after the differential a brief note describing the red cells, white cells, with a rough estimate of the num- ber of platelets, and any unusual cells or degenerated and otherwise unrecognizable forms. (d) All atypical or questionable cells are to be sketched and their position marked on the smear by the ink-spot method or on the vernier scale of the mechanical stage. (e) A good smear of each case, properly Labeled must be in the student's possession, to be handed in with the history. A clean cut is made with a Dock's lancet across the skin striae of the finger tip or the edge of the ear lobe sufficiently deep to produce a free drop flow of blood. Technic for Counting Erythrocytes.-Hold the high dilution pi- pette horizontally and touch the tip of the calibrated stem to a Routine Methods of Blood Study LABORATORY ROUTINE 85 fresh drop of blood. Allow the blood to be drawn into the stem by capillary to the 0.5 mark. Carefully touch the tip of the pipette to the skin of the palm of the hand to wipe off any excess of blood. Draw up Hayem's solution to the 101 mark at the same time rotating the pipette in order to get a mixing from the addition of the first drop of diluting fluid. Hold the pipette with one end pressing against the thumb and the other against the middle finger. Shake thoroughly at the same time rotating with a wrist movement. The counting slide, which is at present usually of a Biirker type or modification, is placed in a perfectly horizontal position in which it must be kept after the addition of the cell suspension. The stage of the microscope is, therefore, the preferable place. The cover glass is placed in position resting on the glass platforms which project exactly 0.1 mm. above the floor piece upon which the area is ruled. There is a moat on either side of the floor piece separating the latter from the platforms. The floor piece pro- jects beyond the adjusted coverslip in order to facilitate the ex- act filling of the counting chamber. The contents of the diluting pipette are then thoroughly mixed as above described and the few drops in the stem expressed on filter paper by using as a bulb the attached rubber tube kinked a few centimeters from the pipette. A drop is then placed on the projecting floor piece and capillarity will cause the space between the floor piece and the cover slip to be promptly filled. Time should not be lost between the mixing and the transfer to the counting chamber because of the error introduced by the settling out of the cells. Furthermore, the fluid suspension should just fill the count- ing chamber and not bulge out or span the moat. Allow the cells to settle over the ruled area and note that the general distribution is uniform. With the central square of the ruled area in the microscopic field count the cells in four columns of twenty small squares each making a total of eighty small squares. It is preferable to select two columns running in each of the two directions of the field. It is essential to include in the count the cells that touch one end and one side even though they appear out- side, along with those contained in the column and to disregard all cells which touch the other end and the other side, even though they are apparently within the column. All counts should be veri- fied. The counting chamber and cover glass should be washed in 86 METHODS IN MEDICINE distilled water and dried with a clean soft cloth. The pipette should be thoroughly shaken again, the drops in the stem dis- carded, a thoroughly mixed drop selected and the counting repeated. To calculate the number of red blood cells per cubic millimeter of blood, from the count of the eighty small squares, it is only nec- essary to multiply by 10,000, that is, to add four ciphers. The reason for this is as follows: Each small square has an area of 1/20 mm. x 1/20 mm. or 1/400 sq. mm.; and as the depth is 1/10 mm. the volume would be 1/400 x 1/10 or 1/4000 c.mm. Since the dilution is one part of blood to two hundred of Hayem's solution, the number of cells found would be only 1/200 the actual number for that volume of 1/4000 c.mm. In other words the vol- ume of whole blood represented in the counted volume is 1/4000 x 1/200 or 1/800,000 c.mm. Since, however, eighty squares were counted, the number represents the count of 80/800,000 c.mm. or 1/10,000 c.mm. of whole blood. Consequently the multiplication of the number of red cells in 4 columns or 80 small squares by 10,000 gives the number of red blood cells per cubic millimeter of whole blood. Technic for Counting Leucocytes..-The low dilution pipette is used in making the white count in the same way that the high dilu- tion pipette was used for the red count. However, % per cent acetic acid is used as the diluent and the dilution is usually 0.5 to 11, that is, 1 to 20, or in some pipettes 0.5 to 21, that is, 1 to 40. All the technical points applied in red cell counting are also im- portant steps in the counting of white blood cells. The number of leucocytes in each of the four 1 mm. x 1 mm. squares at the corners of the central ruled square (Neubauer ruling) are counted and the average calculated. This average number multiplied by 200, if the dilution has been 1 to 20, or 400, if the dilution has been gives the number of leucocytes per cubic millimeter. This derivation is more simple than that for the red count. The large squares have an area of 1 mm. x 1 mm. or 1 sq. mm. and the depth is mm- the volume would be 1 x %0 or %o cu. mm- Since the dilution is 1 to 20 or 1 to 40 the volume of whole blood represented in the amount counted is %oo or %00 cu. mm. Consequently the multiplication of the average number of cells counted multiplied by 200 or 400 according to LABORATORY ROUTINE 87 the dilution is the number of white blood cells per cubic milli- meter of whole blood. If the leucocyte count is above 50,000 the erythrocyte count which is, as done above, a total cell count, must be corrected by the subtraction of the leucocyte count. Estimation of Hemoglobin The Tallquist Scale is of value as a rapid clinical method of estimating hemoglobin when the simple directions are carefully followed. The skin should be free of perspiration and grease, the puncture or incision deep enough to allow the blood to ap- pear drop by drop without the use of much pressure. One of the specially prepared filter papers, supplied in the booklet with the scale, is brought into contact with a fresh drop of blood. The blood should be slowly taken up by the paper until thoroughly absorbed. It is often advantageous to make two stains on the ab- sorbent paper, both preferably in the same half and with a distance of about two centimeters between the centers. The centers of the perforations in the scale are two centimeters apart, and so with two stains at this same distance, two comparisons can be made at the same time. The sheet is folded down the middle, in order to have a clean white background for the stains. Comparisons with the scale either through the perforations or at the sides are to be made only when the humid gloss has disappeared indicating that the blood is thoroughly absorbed. The scale and stain should be illuminated by daylight reflected from their surfaces and preferably coming from behind the one who is making the examination. The percentage is read directly from the scale. The Sahli Method is, however, more accurate and quite easily performed. The standard tube of acid hematin should always be shaken in order that any hematin hydrochloride that has precipi- tated might be redissolved and the color returned to standard in- tensity. Decinormal hydrochloric acid is placed in the graduated diluting tube for the unknown up to the level marked 10. Exactly 20 c.mm. of fresh blood are then collected in the Sahli pipette and discharged into the N/10 HC1 in the graduated tube for the unknown. The Sahli pipette is then rinsed with the H/10 HC1 into the graduated tube several times. The acid hematin will form promptly. Then 88 METHODS IN MEDICINE the unknown solution should be diluted with distilled water until the color of the unknown matches exactly that of the standard. The level of the diluted unknown indicates the percentage of hemo- globin. Computing the Color Index.-The color index is the ratio of the percentage of hemoglobin to the percentage of red blood cells. The red cell count of 5,000,000 is taken as 100 per cent consequently the percentage of red blood cells present can be rapidly calculated by striking off the five right hand figures of the red count and multiplying what is left by two. The normal index is unity. Study of the Morphology of the Blood.-The preparation of good blood smears requires more than exact technical direction. How- ever, a few principles should be kept in mind. The first essential is to have absolutely clean % in. sq. No. 1 cover glasses or slides. Soap and water, acid alcohol, distilled water and 96 per cent alcohol used in turn, with the latter retained as the storage fluid, usually assure clean glassware. The cover glasses are removed from the storage alcohol flamed or dried and polished with a fresh clean, lint-free cloth. When possible heating in a dry air sterilizer should be carried out. The cover glass should always be handled with clean, dry forceps, or by the corners only, even though the fingers are clean. Holding the cover glasses, by their diagonal corners, between the thumb and index and middle fingers, touch the one cover glass to a small drop of freshly drawn blood. Care should be taken not to touch the patient's finger or any finger with the flat side of the cover glass that is to receive the blood film. Taking the second cover glass, by the corners, allow the first, with the blood on its under surface, to drop upon the second so that all corners project. As soon as the blood film stops spreading draw the cover glasses apart with a quick even horizontal pull. Fixing and Staining of Blood Films.-The blood films on cover or on slides are air dried. The preparations should be turned film side down during the drying to prevent the collection of dust upon the specimen or the destruction of the smear by flies. When only a few films are being prepared, the desirable rapid drying can be best accomplished by waving the specimen through the air. Special fixation of the preparation is not necessary in the routine work in which stains dissolved in pure methyl alcohol, such as LABORATORY ROUTINE 89 Wright's, Jenner's, or Leishman's, are used, as the addition of the stain acts, during the first minute in which it is undiluted, also as a fixative. The preparations with the film side up are supported on corks in precipitation dishes and covered with the polychrome stain in methyl alcohol. Forty-five seconds to one minute are al- lowed for the fixation and then an equal volume of distilled water is added. The diluted stain must not run over the edges and must show a green metallic sheen or film on its surface. The staining should be completed within three or four minutes after the addition of the distilled water. The stain should be washed or floated off, by running a small stream of water or the preparation in place on the cork in the precipitating dish. The washed film should be of a coral pink tinge. The specimen is dried between sheets of ab- sorbent paper and mounted in cedar-wood oil or balsam. The stained smear is then studied with the oil immersion lens. The relative number of minute spheric or ovoid granular, dark, lilac-colored platelets should be noted. The intensity of the pink color, as well as the shapes and sizes of the erythrocytes, should be noted. Polychromatophilia, basophilic stippling, nuclei, Howell Jolly bodies, and Cabot's rings, as well as intracellular parasites should be looked for. A differential count of at least 200 leucocytes should be made. The polymorphonuclear cells have tri- or bi- lobulated deeply staining bluish purple nuclei with fine fawn- colored neutrophilic granules; or coarse, irregular, red eosinophilic; or large blotchy purple basophilic granules. The large immature and small mature lymphocytes have deep purple blue nuclei surrounded by a narrow rim of robin's egg blue protoplasm which may show a few fine reddish purple azurophilic granules. The endotheliocytes, made up of large mononuclears and transit!onals, are the largest cells encountered. They have single round oval or indented, eccentri- cally placed, sharply defined, uniform purplish blue nuclei with a relatively wide zone of uniform pale blue or gray blue to colorless protoplasm which may contain a few large or many fine pale azure to reddish granules. The pathologic leucocytes to be differentiated are of myeloid or lymphoid origin. The myeloblasts have large, round or oval nuclei which are poor in chromatin, contain several rather indistinct nucleoli and stain bluish purple. The nuclei are fairly well de- marcated, but still not sharply defined, as the nuclear membrane 90 METHODS IN MEDICINE is indistinct. The cytoplasm contains no granules, is usually only very moderately abundant, characteristically smooth, but occa- sionally finely reticular, and takes a bluish gray color. Myelocytes have the characteristics mentioned for myeloblasts, except that the protoplasm contains either the fine fawn colored neutrophilic, or the coarse red eosinophilic, or the larger blotchy purple basophilic granules. The myelocytes like the polymorpho- nuclear cells are recorded in groups according to the types of granules. Lymphoblasts, lymphoidocytes and abnormal lymphocytes are at times identified only with difficulty. Young lymphoblasts, though large, are usually smaller than young myeloblasts. The nucleus and cytoplasm are often not well differentiated and stain irregularly diffusely but lightly. The nuclei are oval or notched, stain faintly and usually contain three to five nucleoli or they may be frag- mented. The cytoplasmic ring is narrow, lobular and often stains more deeply basophilic than the nucleus. The cells are very fragile and consequently many degenerated forms are met with. Degenerated cells, those beyond recognition, are not counted in the differential count, but are noted separately. Abnormal nucleated red cell forms as microblasts, normoblasts, megaloblasts, gigantoblasts are counted. Abnormal sizes of non- nucleated red cells, microcytes and macrocytes, (anisocytosis) oval forms and bizarre shapes (poikilocytosis) are noted. The Study of the Spinal Fluid The specimen of spinal fluid is usually secured by lumbar punc- ture, which procedure is to be performed only by the interne him- self or under his direct supervision. An ophthalmoscopic examination for the detection of optic disc changes, indicating increased intracranial pressure, should precede every lumbar puncture. In the presence of evidences of increased intracranial pressure the lumbar puncture should be done only after consultation and only by an expert, if it is done at all. Lumbar puncture is performed with the patient either sitting up on a high stool with his feet on one of the last rounds of the stool in order to flex his thighs on his abdomen and bow his lower spine backward; or if the patient is unable to sit up he is placed in a right lateral Sims positions with his thighs flexed on his abdomen and LABORATORY ROUTINE 91 his head flexed on his chest. The backward curved spine is brought to the edge of the bed or table and kept from sagging laterally to the right by a sand bag placed on the table just above the right iliac crest. The patient should be held in this position by an orderly who can best restrain the patient by standing on the side opposite the operator and placing his left arm. at the back of the patient's neck and his right arm in the bends of the patient's knees. Palpate the iliac crests and mark them with a swab of tincture of iodine, and at this level paint a skin area the size of the palm of the hand, in the mid-line over the spinous processes. Scrub the hands as for a surgical operation. Remove the excess of iodine with alcohol. Select the first interspace below the level of the tops of the iliac crests. Produce a pressure ischemia of the interspinous tissues with the thumb of the left hand. Remove the thumb with a jerk, touch the area with alcohol, and with steady pressure insert the needle, which is held between the index and middle fingers of the right hand and backed by the pressure of the right thumb on the head of the stylet. The needle kept at right angles to the tangents of the spine at the point of insertion will usually enter the spinal canal without difficulty. A sudden jerk will be felt as the needle penetrates the interspinous ligament and the spinal dura mater. Withdraw the needle a millimeter or so and slowly and carefully remove the stylet to guard against a sudden release of pressure. In case no fluid is obtained, the stylet is reinserted and the needle partially withdrawn, the direction of the needle cor- rected or a slightly different direction chosen to compensate for any curves, and the puncture again attempted. Two to five c.c. are collected in each of three small test tubes for examination. If cultures are desired the spinal fluid should be al- lowed to drop from the needle directly into the culture media. After the puncture, the patient should be placed in a bed the foot of which is elevated 6 to 12 inches, and kept in this position from 6 to 24 hours. Methods of Examining Spinal Fluid The specimen of spinal fluid should always be examined as soon as possible, preferably within an hour from the time it was with- drawn. 92 METHODS IN MEDICINE The amount is estimated roughly. The clearness, consistency and color are noted. The Cell Count is only reliable in fresh warm fluid, which has been obtained without any hemorrhage whatsoever. The unstained and undiluted spinal fluid can be used directly to fill the counting chamber and the number of cells in the whole ruled area (9 sq. mm.) counted. Since the depth is %o mm., the number counted would be the number in %0 of a cu. mm. volume, from which the number in 1 cu. mm. can be readily calculated. The cells are ab- solutely identified by the ameboid movements which can be noted with the high power objective. A crystal of Unna's methylene blue or gentian violet or fuchsin dissolved in 1 c.c. of spinal fluid before it is placed in the counting cell will aid in the identification of the cells. Clearing and the decolorization of contaminating red cells can be accomplished by moistening the low dilution pipette with glacial acetic acid, blowing out the excess of fluid and drawing up the roughly mixed spinal fluid, mixing, allowing it to stand for a minute and counting the cells disregarding the very slight dilu- tion incurred. Any cell count above 6 per cu. mm. should be con- sidered suspicious and above 10 cu. mm. should be considered pathological. A smear should be made of the sediment of a fresh specimen, staining with Wright's stain, and a differential count of the small and large mononuclears and the polymorphonuclears should be made. The Determination of Excess Globulin content is made by tests which do not react to the normal concentration of 0.2 to 0.5 gm. of globulin per liter. The spinal fluid must be absolutely free from blood in order to have the tests mean anything. Pandy's test consists of adding 1 drop of cerebrospinal fluid to 1 c.c. of Pandy's reagent (a saturated aqueous solution of phenol crystals that has been incubated for 24 hours). A bluish white cloud is positive for excess of globulin. The test, however, is a bit too sensitive. Poss-Jones' test consists in placing 0.3 c.c. of cerebrospinal fluid over 0.3 c.c. to 1 c.c. of saturated ammonium sulphate solution. A milky cloud or opaque ring indicates excess globulin in proportion to its concentration. Nonne-Apelt test, Phase 1, is similar to the Ross-Jones' but the fluids are mixed instead of being layered. The positive reaction is LABORATORY ROUTINE 93 the formation of a precipitate. If this forms it is filtered off and Phase II is carried out. This consists in adding 1 drop of 10 per cent acetic acid and boiling; a precipitate forming under these con- ditions indicates the presence of serum albumin which is always pathological. Dextrose is normally present in 0.04 to 0.05 per cent and never above 0.10 per cent. It is tested for qualitatively by using about 1 c.c.,-that is twice as much spinal fluid as urine in Fehling's or Benedict's tests. For quantitative estimations the Blood Sugar Meth- ods (See Part II) are employed. The dextrose content of the spinal fluid is normal in poliomyelitis; diminished in tuberculous and chronic meningitis; and absent in pneumo-, strepto- and acute men- ingococcus meningitis as a rule. Urea and Chlorides are present normally in concentrations of 20 to 40 mg. per 100 c.c. and 70 to 75 mg. per 100 c.c. respectively. The amounts are determined by the Blood Chemical Methods (Part 11). Both urea and chlorides are increased in uremia. Bacteriological Examinations Smears of the sediment or coagulum are stained with Gram's stain and the Ziehl-Neelsen stain. Besides the meningococcus and tubercle bacillus, pneumo-, strepto-, and staphylococci, influenza and typhoid bacilli, streptothrix, and blastomyces must be thought of as meningeal invaders. In tuberculous meningitic fluid a pellicle or coagulum hanging down from the center of a tube of fluid, that has been set aside for 6 to 12 hours, is quite characteristic and also collects the tubercle bacilli and shows them after acid-fast staining. Cultures of the spinal fluid are made on special media depending upon the organisms suspected to be present. Animal inoculations are also made in selected cases. The Wassermann, colloidal gold, and gum mastic tests are to be done on all spinal fluids. These tests are to be performed only by those specially trained in serologic work. The Study of Other Body Fluids The situations of abnormal collections of fluids are determined by physical signs, which may or may not be corroborated by x-ray findings. It is usually best to make an exploratory puncture, under 94 METHODS IN MEDICINE strict aseptic precautions, with a sterile 10 c.c. or 20 c.c. Luer syringe and needle of moderate or even large bore. Sufficient fluid can be obtained in this way for bacteriologic studies and, if a few crystals of sodium citrate or potassium oxalate are added, for cyto- logic and even for chemical studies. Thoracentesis.-The aspirating outfit should be complete and preferably all attached, with the vacuum bottle in the system. The heavy glass two liter aspirating bottle is fitted with a tightly fitting rubber stopper that carries two glass or metal delivery tubes with rubber attachment tubes which can be tightly clamped. The vacuum may be produced by pumping with an aspirating outfit pump or by rinsing the bottle with water, then with alcohol just enough to moisten the whole inside, then igniting the alcohol at the neck and allowing the blue flame to run down to within a few centimeters of the bottom and then quickly inserting the rubber stopper with the delivery tubes clamped tightly. If a sterile speci- men is to be collected, a sterile flask with two delivery tubes in its stopper is temporarily attached by sterile tubing to the sterile large bore needle on one side and to the free end of a vacuum bottle delivery tube on the other hand. This sterile flask can be removed when filled by clamping the tube from the needle and the tube from the aspirating bottle and a plain glass tube substituted to complete the system. The patient should be sitting up when this is possible. The skin in the region of the angle of the scapula of the affected side is surgically prepared with tincture of green soap, alcohol, and iodine over an area about the size of the palm of the hand. The scapula is drawn aside by having the patient place his hand of the affected side on the opposite shoulder. This interspace at the angle of the scapula, which is usually the seventh, is the usual site selected and the needle is thrust in either a few centimeters to the outside or just inside the angle of the scapula. Skin anesthesia with 1 per cent procaine may be produced, but is usually not necessary. Care should be taken to pierce the intercostal muscles and pleura in the center of the interspace so as not to strike the periosteum of the rib. Do not remove more than 750 to 1000 c.c. at a time. Any coughing, or pain, or distress is an indication for the withdrawal of the needle. Should acute pulmonary edema develop, it should LABORATORY ROUTINE 95 be treated by an intramuscular injection of 1 c.c. of adrenalin fol- lowed by a %o gr. dose of atropine. Pericardial paracentesis must be done with the greatest care. The puncture is most safely made at the left border of the super- ficial cardiac dullness in the 5th interspace, if the diaphragm is in normal position; in the 6th interspace if it is low. The needle should be introduced almost in a sagittal plane and directed but slightly toward the midline. The advance of the needle must be halted when resistance is no longer encountered or when the heart is felt beating against the needle. In cases in which there is a distinct widening of the cardiac dullness to the right with an obtuse cardiohepatic angle puncture in the 4th right interspace just to the right of the sternum may be more successful, but it is a bit more dangerous because of the nearness of the thin walled right heart chambers. Abdominal paracentesis requires no vacuum bottle in most in- stances. The sitting posture at the edge of the bed is the prefer- able position. The patient should empty his bladder. The pres- ence of peritoneal adhesions makes the puncture quite a precarious undertaking; otherwise, however, there are few dangers. Points in the middle horizontal plane of the triangle formed by the umbilicus, pubis and left anterior spine are in the zone of safety. The skin of the lower abdomen is prepared as for a surgical operation with tincture of green soap, alcohol, and iodine. The skin may be asep- tically anesthetized with sterile 1 per cent procaine and a small incision made with a scalpel and the sterile trocar introduced. The trocar may be introduced directly without the incision. The fluid for bacteriologic and cytologic study should be collected first. A rubber tube is then attached to the trocar from which the stylet has been removed, and the fluid is collected in a bucket on the floor. An abdominal binder should be gradually tightened as the fluid is removed. This will facilitate the removal and guard against splanchnic engorgement from the release of the intraabdominal pressure. The Examination of Body Fluids The physical characteristics are noted; the amount is recorded; the color is noted, and attempts are to be made to establish the 96 METHODS IN MEDICINE cause of the color; the transparency or turbidity is also noted and the cause of cloudiness should be determined when possible. A red and white cell count should be made of the thoroughly mixed oxalated specimen. Erythrocyte and leucocyte counts are made just as in the case of blood, except that the low dilution pipette should be used, for lower dilutions are necessary. A smear is made from the centrifuged and saline-washed sedi- ment of the oxalated fluid. The smear is stained with Wright's stain and prepared for microscopic examination in a way similar to that employed in the preparation of blood smears. A differential count of the leucocytes is made and the presence of abnormal or atypical or mitotic cells, of pus cells, of red cells, etc., and of bac- teria is noted. Sterile specimens are cultured and injected into animals. The specific gravity is estimated with a urinometer in a specimen that is not clotted. An Esbach-Tsuchiya quantitative estimation of albumin is made, just as in the case of urine except that body fluids usually must be diluted 5 to 10 times. The relative amount of nucleo-albumin or euglobulin is esti- mated by adding a few drops of 5 to 10 per cent acetic acid sol to clear fluid, a very light or a heavy dense precipitate soluble in excess of the acid indicates the relative amount. In the case of chylous or chyliform fluids, the size of the fat droplets should be noted and the amounts of fat that can be ex- tracted and the character of the resulting fluid should be noted. Pathologic Fluids are roughly classified as transudates or exu- dates according to the following criteria. Transudates are the re- sult of stasis, resemble lymph, contain few formed elements (as endothelial cells), have a specific gravity under 1.015 and contain little or no fibrin nucleoalbumin or englobulin and less than 1 per cent of albumin. Exudates are the result of inflammation, contain many leucocytes or lymphocytes, have a specific gravity over 1.015, and contain much fibrin, nucleoalbumin or englobulin and more than 1 per cent of albumin. Ward Routine for Laboratory Specimens 1. The ordering of specimens "to lab" is to be done by the interne, whom the student will consult when specimens are wanted. All LABORATORY ROUTINE 97 specimens ordered "to lab" are deposited in the ward's laboratory ice-box. 2. All utensils and urine containers in the laboratories, except those in the ice-box or on the central table are cleaned by the diener or orderly and placed by him in the utensil room. 3. The container of any specimen labeled "infectious" is sterilized in the utensil sterilizer by the diener. 4. All sputum cups are boiled by the diener before being placed in the utensil room closet. 5. The laboratory linen is in charge of the head nurse on the ward. 6. Specimens are sent to the laboratory without written orders as follows: 1. Urine.- (a) First specimen after admission, stat. (b) Two 12-hour specimens for patient's first day in hospital. (c) One 24-hour specimen each week. 2. Sputum.- / (a) First, or admission specimen. (b) Total sputum each morning. 3. Stools.- (a) First specimen after admission. (b) One specimen each week. 4. Stomach Contents.- Test meal, vomitus, etc., specimens. 5. Any Unusual Specimen.- Especially all vomitus, diarrheal stools, suspected parasites, "casts," hemorrhagic discharges or calculi. Any infectious specimens should be so labeled by the head nurse. Every precaution must be exercised in the proper sterilization and disposal of any such specimens. Any specimens left outside the ice-box, except those on the central table, will be thrown away by the diener. Provision is thus made for the disposal of all specimens which are no longer required for ex- amination. Such specimens should be placed on the disposal shelf and not left standing on the work table when no longer needed. Each evening at 6 the ward ice chest will be cleaned out of the day's specimens. The examination must have been done on these 98 METHODS IN MEDICINE by this time. The ward workers, being responsible, must rescue their specimens before this time and preserve them in their own pos- session or they will be lost. Blood smears or other smears which are of importance in the diag- nosis of particular cases are to be saved for filing with the histories. This is extremely important as a matter of record. The diener will keep the laboratory in order. Workers should assist as per rules. Rules for ward workers are posted in the laboratories. Specimens to be Preserved In order to enable the third year class in clinical microscopy to see all manner of specimens, the cooperation of the resident staff of the hospital and the fourth year students is requested. When pa- tients with any of the diseases mentioned below enter the hospital, or when any of the specimens listed below are obtained, the house officer or the fourth year student should notify the assistant in clini- cal microscopy. Anything considered of interest, whether mentioned in the list or not, should be reported. Urine.- Urine showing Bence-Jones bodies; Diazo reaction; remarkable casts; rare crystals, such as cholesterin, leucin, tyrosin, ammonium biurate and rare forms of uric acid or calcium oxalate. Sputum.- Sputum showing elastic tissue; heart failure cells; Cursch- mann's spirals; Charcot-Leyden crystals; spirochetes or mycelium. Sputum of cases of pulmonary gangrene; ab- scess ; asthma; pneumonia or any of the rare diseases such as spirochetosis, bothriomyeosis, actinomycosis of the lung, etc. Gastric Contents and Vomitus. Stools.- Gastric contents or vomitus showing 11 coffee grounds," blood, sarcinae, yeast moulds or Oppler-Boas bacilli. Any stools showing tarry character, amebae, tubercle bacilli, or any form of parasite or ovum. Stools from ulcerative colitis or mucous colitis cases. LABORATORY ROUTINE 99 Blood.- Blood smears showing eosinophilia, leucocytosis of 25,000 or more; secondary anemia with counts as low as 3,000,000 or any- pernicious anemia case. The laboratory should be notified of blood crises; cases of chlorosis; leukemia, all types; malaria, all types. Transudates and Exudates.- Transudates and exudates of special interest either because of their chemical nature or the presence of formed elements should be preserved. CHAPTER XI EQUIPMENT FOR WARD WORKERS Plan for Conduct of Ward Laboratories.-Owing to the waste of materials in the ward laboratories (2418 and 1418) the following plan for organization of these laboratories is carried out. Each student in the medical section is to be issued a complete set of apparatus for carrying on routine laboratory work on his patients. He will obtain these supplies from the stock room of the Depart- ment of Internal Medicine, Room 2722 Dispensary Building, and will sign a memorandum receipt for them. He will keep this apparatus in his locker in the ward laboratory and will return it at the end of the trimester. Any apparatus which has been broken will be charged against the student on his breakage bill. Glassware broken during the trimester will be replaced by withdrawing from the stock room on the memorandum receipt. The student must provide his own hemocytometer and diluting fluids. Each ward laboratory is equipped with a complete set of reagents and the special instruments necessary in carrying out the routine laboratory work. Certain apparatus, such as microscopes and colorimeters, must be used jointly by the students in the group. It is advisable for each senior student to provide his own microscope and hemoglobinometer. The complete laboratory equipment is checked out at the beginning of each trimester. If any of this special apparatus is lost or broken at the "checking up" at the end of the trimester and the responsible person cannot be located, the cost of the missing material will be pro- rated among the members of the group. Special apparatus on the ward is to be used by the students only under the supervision of a house officer. Expendable supplies, such as chemicals, will be renewed as neces- sary. Notation of chemicals needed should be made on slips provided for that purpose and should be accompanied by the name of the writer. The laboratory supply man makes daily rounds for the pur- pose of keeping the stock of chemicals in the laboratory up to date, 100 EQUIPMENT FOR WARD WORKERS 101 and he will see that the empty bottles are promptly and properly filled. Apparatus to Be Supplied to Each Student The following apparatus will be supplied to each student in the medical group: 1 Glass plate 3.5 x 4.5 cm. 1 Glass stirring rod. 1 Plain glass pipette 2 mm. 1 Graduated pipette 1 c.c. 1 Volumetric pipette 5 c.c. 1 Volumetric pipette 10 c.c. 1 Volumetric pipette 25 c.c. 1 Graduated cylinder, 50 c.c. 2 Esbach albuminometers. 1 Erlenmeyer flask. 1 Beaker. 1 Test tube rack. 1 Test tube brush. 1 Test tube holder. 6 Test tubes. 4 Centrifuge tubes. 1 3" funnel. 1 Staining jar. 1 Precipitating dish. 1 Bottle Wright's stain. 1 Sediment glass. 1 Evaporating glass. 1 Box with 25 glass slides. 1 Oz. % in. sq. No. 1 cover slips. 100 Round filter papers. 12 Large sheets filter paper. Equipment in Each Ward Laboratory 2 Microscopes. 1 Mechanical stage. 1 Hemometer, Sahli. 1 Colorimeter for 'phthalein, (Hellige and Dunning). 1 Graduated cylinder 1000 c.c. 2 Urinometers with cylinders. 2 Fermentation tubes. 3 Burettes. 3 Iron stands with rings and burette clamps. 3 Bunsen burners. 3 Tripods and wire gauze. 1 Copper bar. 1 Mortar and pestle. 1 Set of bottles containing chemicals used in laboratory routine. Special Apparatus Available on the Wards and in the Central Medical Supply Room In ward cabinets and in cases in the stock room. A card index of special apparatus is kept on the interne's table in each ward. 102 METHODS IN MEDICINE Instruments and apparatus used in any routine or special tests, must be returned to their proper places promptly on completion of the examinations for which they were used. Blood.- 4 Hemoglobinometers (Dare). 2 Miescher-Fleischl Hemoglobinometers. 1 Kontrast Hemoglobinometer (Schlesinger). 1 Coagulometer (Modified Boggs'). 1 Blood Alkalimeter (Engel). 2 Viscosimeters (Hess). 1 Hematocrit. Circulation and Respiration.- 3' Polygraphs (Jacquet). 1 Polygraph (Mackenzie). 1 Chest apparatus for Jacquet Polygraph. 1 Time Marker (Jacquet). 1 Curve Analyzer and Measuring Apparatus. 2 Slide Rules. 2 Centimeter and millimeter rules. 2 pairs Dividers. 1 Electrocardiographic Outfit (Hindle). 1 Blood Pressure Machine (Erlanger). 1 Blood Pressure Machine (Riva Rocci). 1 Leg cuff for blood pressure estimation. 3 prs. Dumb-bells for exercise tolerance tests. 2 Multiple Stethoscopes (Bowles). 1 Spirometer or Pneumotometer (Gobel). 1 Spirometer (Kroh Krough). 1 Respiration Recording apparatus. 1 Smoked paper drum outfit. 1 Alveolar C02 Tension apparatus. 1 Alveolar C02 Tension apparatus. 1 Van Slyke's apparatus. 2 Basal Metabolism outfits. 1 Hydrogen-ion concentration apparatus. 1 Potentiometer. 4 Colorimeters, Duboscq, Benedict, etc. 1 Nephelometer (Bausch and Lomb). EQUIPMENT FOR WARD WORKERS 103 Urine.- Urinometers with cylinders. Urine Specific Gravimeters. Urinoglucosometers, Fermentation (Stern). Uroglycometer. Saccharimeter (Einhorn and others). Fermentation Tubes (Muenzer, Schmidt, etc.). Ureometer (Doremus-Hinds and others). Ammonia Apparatus (Folin). Nitrogen Digesting Apparatus (Kjeldahl). 2 Polariscopes. 2 Water baths. Other Special Apparatus 1 Cystourethro and endoscope (Brown-Buerger). 1 Peritoneoscope. 1 Oesophagoscope. 1 Spectroscope. Sigmoidoscopes and Proctoscopes. Microscopes and mechanical stages. Dark-field illuminator outfit. Warm stage (Strickler-Leitz). Camera Lucida. Miscellaneous Apparatus Oesophageal Bougies. Gastro-duodenal tubes (Rehfuss, etc.). Stool separator (Strauss). Sputum table, (Koenig). Half Black glass dishes and plates. Scoliometer. Protractor. Head Calipers (Bertillon). Pelvic Pelvimeter. Trocars, DeGuy and Universal. Cautery, Electric. Camera, Graflex with revolving back. 104 METHODS IN MEDICINE Eye.- Ophthalmoscopes (May's) (Wappler). Perimeter for visual fields. Exophthalmometer (Hertel). Wool color test yarns. Visual acuity charts. Ear.- Tuning forks. Galton whistle. Aesthesiometer. Auroscope (Wappler). Laryngoscope (Wappler). General examining tray, each ward. Neurologic Examining Tray, each ward. Vaginal and rectal examining tray, 14.18 and each ward. Regular Examination Tray Throat mirror. Wooden tongue depressors. Small paper bags. Flashlight. Head mirror. Stethoscope. Tape measure (centimeter). Percussion hammer. Blue and red skin pencil and 6B Venus black pencil Towels (2). Nasal and aural specula. Auscultation towels. Gauze handkerchiefs. Pins. Glass slides. Cotton wrapped toothpicks. Cotton applicators. Alcohol lamp. Matches. Hemoglobin Scale (Tallquist). Ophthalmoscope. EQUIPMENT FOR WARD WORKERS 105 Neurologic Examination Tray A. for testing senses and sensation. 1 vial camphor. 1 vial alcohol (denat.). 1 vial whiskey (small amount). 1 vial syrup or sugar. 1 vial salt. 1 vial pepper. 1 vial quinine. 1 vial acetic acid (dil.). 1 vial peppermint or Wintergreen. 1 vial oil of cloves. 1 vial asafoetida. 1 vial turpentine. 1 bottle 1% Homatropin. 1 pin on a stick. 1 camel's hair brush. Toothpick applicators. Cotton in a medicine glass. Test tubes for hot and cold water. Cards for visual acuity tests. Cards with words "sweet," "sour," "salt," "bitter," "hot," "cold" printed on them. 1 Dynamometer. 1 Dividing Compass. 1 Galton whistle. 1 Hagedorn needle. 1 Set tuning forks. 1 Ophthalmoscope. Pocket knife, spoon, pencil, comb, mouth whistle, scrap paper. Vaginal or Rectal Examination Tray 1 Pair sterile gloves. 1 right glove. 1 left glove. 1 towel. 1 tube vaseline. 106 METHODS IN MEDICINE 1 powder box. 1 bi-valve speculum. 1 pr. uterine dressing forceps. Electric proctoscope with slides, cotton, sponges, and basin. Examination trays must be kept intact and not stripped of their contents or scattered about the wards. Students must be considerate of the nurses' time, especially in the time selected for doing a physical examination which requires chaper- onage. CHAPTER XII PROCEDURES TO BE UNDERTAKEN IN THE MORE COMMON TYPES OF CASES In order to facilitate a prompt and complete study of each case, the following minimum requirements are outlined: All Patients upon admission, shall have recorded within twenty- four hours. 1. A complete history. 2. A detailed physical examination, including blood pressure reading. 3. A blood specimen withdrawn for the Wassermann test. 4. An erythrocyte count; a leucocyte count; and a hemoglobin estimation (Tallquist and Sahli). 5. An analysis of at least a fresh admission specimen of urine. 6. A phenolsulphonephthalein test. 7. A stool examination. 8. A sputum examination. All significant findings should be promptly verified. In addition special cases are to have special examinations. All specimens are to be carefully labeled and preserved. Pulmonary Cases.--Sputum examination every day. Note amount. (Tubercle bacilli, influenza bacilli, pneumococci, spiro- chetes by the dark-field, elastic tissue.) Complete examination, physical, chemical, cytologic, and bac- teriologic, of any pleural fluid obtained. Tuberculin intradermally in suspected tuberculous cases. Erythrocyte count, leucocyte count, and hemoglobin estimation once each week. Urine examination twice each week; daily, if abnormal. Stereoscopic x-ray plates of the chest after recording carefully the physical signs. Pneumonia Cases, in addition to the above. Sputum cultures and typing of the organisms. Bidaily blood pressure readings (a.m. and p.m.). (Systolic and diastolic.) 107 108 METHODS IN MEDICINE Daily urine analysis with quantitative chloride estimations. Leucocyte count daily or oftener. Erythrocyte count and hemo- globin estimation once a week. Intracutaneous reaction to pneumotoxin. Gastrointestinal Cases.-Careful examination of every stool speci- men. Examination of vomitus and contents of the fasting stomach and test meal specimens. Amounts, gross and microscopical examina- tions and chemical analyses. Special chart. Study of duodenal contents and bile. Gastrointestinal x-ray studies after taking barium by mouth. Erythrocyte count, leucocyte count, differential count (500 cells) and hemoglobin estimation once a week. In all jaundiced cases study bile pigments in the blood plasma to differentiate obstructive jaundice from hemolytic jaundice. Typhoid Fever Cases.-Blood, urine and stool cultures. "Widal agglutination tests. Chart daily fluid intake and output, and the food or caloric intake. Blood pressure daily and at once on suspicion of perforation or hemorrhage. Leucocyte count every other day, or hourly if perforation or hemorrhage is suspected. Erythrocyte count and hemoglobin weekly or at once if hemorrhage is suspected. Urinalysis daily (diazo reaction, acetone bodies). Diabetes Mellitus Cases.-Complete quantitative analyses of the urine daily. Chart the total quantitative sugar output for each 24 hours, also note the percentage as grams per liter. The organic acid output including beta-hydroxybutyric acid, di- acetic acid and acetone. The total nitrogen output for the D:N ratio. Chart fluid intake and output, dietary values of protein, fat and carbohydrate, along with the chemical and special quantitative lab- oratory findings. The blood sugar levels, the blood carbonate and the alveolar CO2 values. Blood fat and blood acetone bodies in selected cases. Erythrocyte count, leucocyte count and hemoglobin estimation once a week. PROCEDURES FOR MORE COMMON TYPES OF CASES 109 Endocrine Cases.-Basal metabolic rates. Sugar tolerance tests (to be charted). Liver function tests. Pharmacologic tests (to be charted). X-rays of skull for sella turcica, hands in pituitary cases, ad- renals for calcification in Addison's disease, and retromanubrial region for persistent thymic rests. Exophthalmetric measurements (Hertel) Ophthalmoscopic exami- nation and visual field charts. Photographs. Careful differential blood counts of at least 200 cells. Cardiac, Nephritic and Hypertension Cases.-Cardiac charts, pulse deficit charts, complete 12 hourly urinary charts and blood pressure charts are to be kept up to date, as a graphic record of the patient's clinical progress. Complete examination of all 12 hour day and night specimens with quantitative albumin and chloride estimations and a daily microscopical examination of the sediment of a small, freshly-voided specimen. Special chemical examination for ammonia, urea, uric acid and creatinine in selected cases. Repeated phenolsulphonephthalein tests at weekly intervals. Blood chemical studies as total values of blood nonprotein nitro- gen, urea, uric acid and creatinine and chlorides. Pulse tracings where there is a question of alternation. Electrocardiograms, teleroentgenograms and orthodiagraphic ex- aminations. Vital capacity and exercise tolerance tests. Erythrocyte counts, leucocyte counts and hemoglobin estimations once a week. Teeth, tonsils, sinuses, genito-urinary tract and gastro-intestinal tract should be thoroughly investigated and any foci of infection should be treated and eradicated. Diseases of the Blood or Hemopoietic Systems Anemias; leukemias; polycythemias; leucopenias; Banti's disease; hemolytic familial jaundice; Hodgkin's disease; purpuras; multiple myeloma; cancerous metastases to the bone marrow, etc. 110 METHODS IN MEDICINE Careful differential blood count of 500 cells. To be repeated daily, within a few days or within a week, as seems desirable. Leucocyte counts, erythrocyte count and hemoglobin estimation with the color index figured out at least biweekly, in certain cases more frequent examinations may be required. Vital staining and peroxidase staining should be applied to prep- arations of all bloods. Platelet counts, bleeding time and coagulation time and estima- tions and fragility tests are to be applied in purpuric and hemolytic cases. Bile pigments in the blood plasma are to be studied in all cases in which there is a question of hemolysis or icterus. The quantitation of urobilinogen, urobilin and bile pigments in the duodenal contents, feces and urine is of importance. Gastric analysis should be done in every case of anemia and re- peated if an achlorhydria is found. Stool examinations should be repeatedly made and blood, pus, parasites, and ova searched for. The patient should be carefully examined for chronic bleeding hemorrhoids or foci of infection. All patients with anemia should have blood grouping tests car- ried out and the group verified. In cases where transfusion is to be done besides the grouping, the bloods of the donor and recipient must also be directly matched. In suspected bone marrow lesion cases x-rays of the long bones should be made and the urine and blood serum should be tested for Bence-Jones protein. PART II CHAPTER XIII SPECIAL PROCEDURES TO BE APPLIED IN GASTRO- INTESTINAL CASES GASTRIC FUNCTION TESTS Admission Tubing'.-The large straight stomach tube is to be passed upon the completion of the history and physical examina- tion of any case where there is a question of gastric stasis from pyloric obstruction. The contents of the stomach are usually ex- pressed by having the patient exert pressure upon the stomach by means of his abdominal muscles and diaphragm. Or, after deep inspiration, the patient is made to bend forward suddenly. If these maneuvers are unsuccessful, syringe suction should be at- tempted. The contents obtained should be examined microscopically at once and then set aside for chemical examination. With the tube retained in place, lavage should be carried out until the washings return clear. In this way no time is lost in making a diagnosis and at the same time active therapeutic lavage removes the irritating products of fermentation, and often tends to relieve the spasmodic part of the pyloric obstruction. The Retention Test is carried out with the test meal by giving the patient spinach (short cut) the evening preceding the exami- nation. In cases of retention the fasting contents will show the cellulose indicator macroscopically. The Gastric Fractional Examination is routinely done in the morning after a twelve-hour fasting period. The regular test meal is to be the Dock test-breakfast consisting of 30 gm. of dry shredded wheat biscuit, to be chewed by the patient, and 400 c.c. of water. The advantage in this meal lies in the fact that the shredded wheat contains no lactic acid; is clean and uniform in its make-up, easy 111 112 METHODS IN MEDICINE to keep and easily obtainable, and obliges mastication and insali- vation. It should be "crisped" by warming just before it is served. Boas recommended rolled oats, as they contain no lactic acid. The meal to consist of 30 gm. of rolled oats boiled in 500 c.c. of water with salt added to taste. This meal has been modified to the extent of taking 30 gm. of oatmeal and 800 c.c. of water and boiling the mixture down to a volume of 400 c.c. and adding no salt ("Boas' Gruel"). Ewald's test-breakfast is advocated by many because of its eco- nomical simplicity. It consists of two % x 3 x 3 inch slices of white bread (50 gm.) with crust cut off and 350 c.c. of water. The Regular Dinner Test Meal is sometimes used, and samples are secured after two and four hours. The ordinary regular dinner with a portion of spinach added may be used for this. Other Special Test Dinners are as follows: Kussmaul Test Dinner. 500 c.c. water or tea without cream or sugar. 40 gm. toast. 1 bowl cereal without milk. 50 gm. meat (any kind). Riegel Test Dinner. 400 c.c. meat broth soup. 150-200 gm. beefsteak. 50 gm. potatoes. 35-70 gm. stale bread or rolls. Details of Procedure and Methods of Aspiration of the Gastric Contents for Analysis.-The patient is to be given certain specific directions on the evening before the examination. Just twelve hours previous to the time at which the tube is to be passed, that is, at 8 or 9 o'clock p.m. a light meal, of one meat sandwich with a heaping tablespoonful of shortcut spinach or twenty raisins, or six stewed prunes, and a glass of water are taken. No food or fluid is to be taken after this until the test breakfast is served. Saliva, postnasal discharge and bronchial excretions must not be swallowed during the period of gastric study. If the gums are at all prone to bleeding, care should be taken to avoid any trauma, even that of brushing the teeth. SPECIAL PROCEDURES FOR GASTROINTESTINAL CASES 113 On the morning of examination, the patient is to be prepared with as little paraphernalia as possible. One small towel should be sufficient, as the mass of rubber sheeting so often used has a very bad psychical effect. A stomach tube is moistened in tap water and the tip placed into the throat, the tongue being de- pressed at this time with a maple stick. The entire fasting con- tents are removed with care and placed aside to be thoroughly examined as soon as possible. From this point on the procedure differs according to which method is followed. If the traditional method, which is advocated in this clinic, is used, the tube is removed and the patient given the test meal and the tube re-introduced forty-five minutes after the meal as will be described later. If the Rehfuss fractional method is to be used, the patient is instructed to work the small tube to the side of the throat, bringing it out into the buccal space behind the last molar where it will interfere very little with the chewing of the test meal. Mucus and saliva collecting in the mouth after the completion of the test meal should not be swallowed. Five to ten c.c. specimens of gastric contents are to be removed every fifteen minutes for two hours, following the completion of the test meal. Gorham has pointed out a physiologic principle that explains in part the great variety of curves obtained by the fractional method in the same individual and in similar pathologic conditions. These deviating curves are still being attributed to secretory variations. The fallacy of the small sample fractional method is shown con- clusively, by clinical and experimental data, to lie in the neglected fact that the gastric chyme is not, in the majority of instances, a homogeneous mixture. The acidity of different portions may vary widely and consequently the acidity of the fractional sample depends on the position of the metal tip of the aspiration tube, and may or may not be representative of the gastric contents re- maining in the stomach. Hence the danger of placing great stress upon the diagnostic values of the curves plotted from the results of fractional analysis. The method of procedure advocated by Gorham on the basis of the above facts differs from the fractional method in that the tube is removed after all of the fasting contents have been withdrawn. The Dock test meal is then given and the tube re-introduced forty- 114 METHODS IN MEDICINE five minutes after the meal and the contents aspirated in 10 c.c. portions in rapid succession until the stomach is empty, the last portion being obtained after the inflation of the stomach with air, the patient lying supine. The acidity of each of these different portions is determined separately and an equal mixture of all samples is used for determining "the average acidity." Thus in order to have true quantitative gastric analysis, the stomach must be emptied completely at a definite time after a standard test meal. The true fractional analysis necessitates the giving of suc- cessive test meals and extracting them, emptying the stomach com- pletely at different intervals as % hour, 1 hour, 1% hours and 2 hours after successive test meals. For ordinary work, the complete withdrawal of gastric contents forty-five minutes after the test meal will suffice, as the obtaining of a true fractional in most instances is impractical, due to the amount of time and effort necessary. Reference: Gorham, F. D.: Arch. Int. Med., August, 1921, xxvii, 434. The String Test.-About 100 cm. of No. 5 braided silk cord with preferably a duodenal bucket or a small split shot fastened to one end is all the apparatus that is required. About 9 or 10 o'clock in the evening, the patient is asked to swallow the duodenal bucket and about 70 to 80 cm. of the thread is to be taken into the digestive tract. The end of the string is fastened to the nightdress. The bucket and string are left in place overnight to be carried into the duodenum by peristalsis while the patient sleeps The entire 70-80 cm. length of the thread must be in the digestive tract before the patient goes to bed. No colored foods or fluids are to be taken after the white silk thread is in place, for stains from such substances cause confusion. The next morning before breakfast the point on the string which is opposite the incisor teeth is marked by a knot. The bucket is then slowly and gently lifted out. The narrowing of the esophagus at the larynx is passed by asking the patient to swallow and with- drawing the bucket during the act. The string, which has in most cases been in a position along the lesser curvature of the stomach passing through the pylorus and extending into the duodenum for about 10 cm., is immediately and carefully examined for blood SPECIAL PROCEDURES FOR GASTROINTESTINAL CASES 115 spots and bile stains. The duodenal contents in the bucket are removed and examined. If a string with a length of 65 cm. or more shows no bile stain, a pyloric obstruction is to be suspected and the test repeated after a dose of atropin (%0 gr.) in an attempt to determine whether the obstruction is due to spasm or organic changes. Tn the case of obstructive jaundice, the absence of a bile stain is significant. Blood stains at about 40 cm. from the teeth, point to ulcer of the cardia; from 44 to 54 cm., to ulcer of the lesser curvature; from 55 to 56 cm., to ulcer of the pylorus, and beyond 57 cm. to ulcer in the duodenum. Two definite brown stains near each other usually indicate the margins of the ulcer. A brownish discolora- tion for a long distance is usually due to different parts of the thread coming successively into contact with the ulcer. The stains can be subjected to the benzidine test for verification. The simplicity of the test recommends it, but opinions vary as to its reliability and negative results are not to be considered as conclusive. Reference: Einhorn, Max: Internat. Jour. Surg., November, 1909, and Medical Record, March 18, 1911. Gastric Ferments.-Rennin apparently plays very little or no part in diagnosis and it is consequently not tested for clinically very often. Pepsin has a minor value in diagnosis, but its quantitative de- termination is not accurate. It usually corresponds in quantity to the hydrochloric acid content. The presence or absence of the fer- ment does not differentiate functional and organic anacidity. It is absent in true achylia gastrica and may be present in small amounts in achlorhydria, though it is usually absent with the anacidity. A rough qualitative test' (Mett's) for pepsin consists in placing a thin disk of the white of a hard boiled egg, (the disk being 1 cm. in diameter and 1 mm. thick, and weighing one gram) in 5 c.c. of acid gastric filtrate (if not acid, add 2 drops of dilute HC1) warmed to and kept at 38° C. Pepsin will cause a disappearance of albumin in two to six hours. For quantitative results, Einhorn's and McClure's methods, as outlined for the estimation of the pro- 116 METHODS IN MEDICINE teolytic activity of duodenal contents may be used. Quantitative estimations should only be considered when the complete gastric contents have been removed. EXAMINATION OF THE DUODENAL CONTENTS Method of Aspiration of Duodenal Contents.-The duodenal tube with a metal tip, and markings to indicate important landmarks, as I at 40 cm. to indicate the distance from the teeth to the cardia, II at 54 cm. the pylorus distance, III at 70 cm. the duodenal dis- tance, is moistened in tap water. The tongue is depressed with a maple stick, the metal tip placed in the pharynx and the patient is directed to swallow. If only the duodenal contents are desired, the patient may be given water to drink to augment the passage of the tube. Water is, however, not necessary and should not be used routinely. With mark I passed, one can feel safe that the metal tip has passed the cardia. As mark II approaches the teeth, the fasting stomach contents are removed. A syringeful of water and then one of air is passed through the tube. The tube is then clamped and with care that there is no retardation due to fixation of the tube from holding it too tightly in the mouth and that in- tentional swallowing is avoided, the tube is left for an hour. During this time, it is best for the patient to be lying on his right side with his hips elevated and reading light literature in order to divert his attention. If at the end of an hour or so, the sign III (70 cm.) is near the lips or inside the mouth, aspiration is attempted. With the metal tip in the duodenum, a clear watery or golden yellow, somewhat viscid, alkaline liquid is generally obtained. The liquid may, how- ever, be acid in pathologic conditions, so that it becomes extremely important to determine that the tip is in the duodenum. The characteristic duodenal "tug" is often present. Collapse of the connecting rubber tube on rapid aspiration suggests the vacuum formation of the duodenum provided the tube is not clogged. After waiting a few minutes and attempting slow aspiration, the duode- num will yield a small amount of fluid. If the tip is in the stomach, there is usually no collapse on rapid aspiration and fluid appears much more quickly. The entrance of air, forced through, is very plainly felt and its position localized by the patient if the tube SPECIAL PROCEDURES FOR GASTROINTESTINAL CASES 117 is in the stomach, but usually not so if the tip is in the duodenum. Two or three swallows of milk or coffee are returned at once on aspiration, if the tube end is in the stomach, while only clear duodenal contents return if the tip of the tube is in the duode- num. The position of the tube, as well as the metal tip, can be definitely localized under the fluoroscope. Duodenal Fractional Examination.-With the duodenal tube in place, the fasting contents are aspirated and examined as outlined below. The test meal of one bouillon cube (Armour & Co.) to one cup of hot water is given by mouth, and aspiration of the duodenal contents performed every half hour, for two hours, after the test meal. The gastric analysis should be completed in advance, in order to acquaint the examiner with the gastric secretory function. The same objections, although with much less basis, might be of- fered against the duodenal fractional, as are mentioned concerning the gastric fractional. Small amounts of duodenal contents may not be representative of the total content as the point of location of the tip in the duodenum is not settled with exactness. Con- clusions must therefore be guarded. The Analysis of the Duodenal Content.-A careful microscopic examination, especially of the fasting contents, is as important as it is for gastric contents. Chemical examination is likewise im- portant. If alkaline, as is usually the case, the degree of alkalinity is determined by titration with one-tenth normal standard hydro- chloric acid with methyl orange or litmus as the indicator. If acid, the degree of acidity is determined just as for gastric contents and both are recorded in the same terms. Estimation of Pancreatic Enzymatic Function Neutralize the duodenal contents if the reaction is acid. Qualitative Estimations For rough examination, qualitative tests may be used. 1. Trypsin.-A small piece of coagulated egg albumen is placed in about 1 c.c. of duodenal contents and kept at 38° C. for a few hours. If trypsin is present, the egg albumen dissolves. 2. Steapsin.-One drop of neutral milk, two drops of water, two 118 METHODS IN MEDICINE to three drops of duodenal contents, and a small piece of litmus agar are placed in a very small test tube. The substances are mixed and incubated at 3'8° C. In the presence of steapsin, fats are split into glycerol and fatty acids and the latter turn the litmus red in twenty to thirty minutes. 3. AmpZopsin.-A boiled starch solution is mixed in equal parts with the duodenal contents or with a strip of starch paper and placed at 38° C. for one-half to one hour. After this, a weak iodin solution is added. Starch gives a blue color, but in the presence of the amylolytic action, a red color of eryth.rodextrin appears. If all the starch is changed, there is only a trace of brown from the iodin. Quantitative Estimations Einhorn's Agar-hemoglobin, Agar-olive oil, and Agar-starch tubes form a convenient method of getting fairly accurate esti- mations. Hemoglobin tubes are made up of 1 gm. hemoglobin powder; 2 gm, agar powder; distilled water q.s. ad 100 c.c. Rub the hemo- globin with about 10 c.c. of distilled water until it is a smooth thin paste, add the agar powder and the rest of the water. This mixture is put into a flask and heated to the boiling point and then drawn by suction into a previously warmed glass tube of 1.5 mm. inside diameter. After the tube and contents are cooled, 3 cm. lengths are cut and sealed at each end with paraffin. Olive oil tubes are made up of 25 gm. olive oil; 2 gm. agar powder; 1 to 2000 aqueous solution of Nile-blue sulphate q.s. ad 100 c.c. Rub the olive oil and agar together, add distilled water enough to make a thin paste, then add the Nile blue sulphate solu- tion. With this mixture, make tubes in the same way as directed for the hemoglobin mixture. Starch tubes are made up of 5.0 gm. starch; 2.5 gm. agar powder; distilled water q.s. ad 100 c.c. Rub the starch in a mortar with water sufficient to make a smooth paste and then add the rest of the water. Make the tubes as directed under the hemoglobin tube procedure. The agar tubes retain efficiency for four to six weeks if kept on ice. If dry, they are unreliable; if old, freshen after removing the paraffin, by placing in water for five minutes before using. SPECIAL PROCEDURES FOR GASTROINTESTINAL CASES 119 Prepared agar tubes for pancreatic enzyme function tests may be obtained from Eimer and Amend, 205 Third Avenue, New York City. Method of Testing.-One each of the hemoglobin, oil, and starch tubes are taken, the paraffin is removed and the three are placed vertically or preferably slightly slanting in a bottle containing five to ten c.c. of duodenal contents, alkaline or neutral in reac- tion. A drop of toluol is added as a preservative and the tubes are incubated at 38° C. for twenty-four hours. At the end of this time, the tubes are inspected for changes. Trypsin changes the appearance of the hemoglobin tube, the ends becoming more or less transparent, the lengths of transparency are measured and recorded in millimeters. Steapsin splits the oil into fatty acids which produce a blue color with the Nile blue sulphate, the lengths of the bluish color at the ends of the tube are measured and re- corded in millimeters. Amylopsin action on the starch tube is estimated by pushing out the starch agar column and dipping it into a weak solution of iodin. The portion of the starch agar column remaining colorless is the part changed to sugar and the lengths of the colorless parts are measured and recorded in milli- meters. References: Einhorn, Max: Am. Jour. Med. Sc., December, 1918, clvi, 817; Jour. Am. Med. Assn., Nov. 5, 1921, Ixxvii, 1471. Friedenwald, J., and Sindler, J.: Jour. Am. Med. Assn., Nov. 5, 1921, Ixxvii, 1469. The most accurate and reliable methods of estimating pancreatic enzyme activity are those of McClure, Wetmore, and Reynolds, which follow. Estimation of Proteolytic Activity of Duodenal Contents Reagents Phosphate Mixture.-Two-tenths molar phosphate mixture of pH 8.4 is prepared as follows: add 20 c.c. of a solution of potassium acid phosphate (KH2PO4) (C.P.), containing 27.234 gm. to the liter, to 980 c.c. of a solution of disodium phosphate (Na2HPO4.2H2O10) (C.P.) containing 35.628 gm. to a liter. The usual C.P. preparations of disodium phosphate, obtainable on the market, contain twelve molecules of water (Na2PIIO4.12 H,O). Such preparations should be thoroughly triturated in a mortar, and then air dried, by spreading out on large filter papers in the 120 METHODS IN MEDICINE open room. In from twelve to fourteen days the salt will lose ten molecules of water and then will be suitable for use as disodium phosphate (Na2HP04.2H20). Phosphate mixtures containing the salt prepared in the manner described will give the proper pn as determined by the use of the potentiometer. Casein Preparation.-(Bosworth, A. W., and Van Slyke, L. L.: Jour. Biol. Chem., 1913, xiv, 203.) Method of preparing ash-free Casein. To dilute separator skimmed milk with seven or eight times its volume of distilled water carefully add dilute acetic acid (6 c.c. glacial acetic acid diluted to 1000 c.c.) until the casein sep- arates completely; after which the clear solution is removed by siphon as soon as the precipitate settles. Distilled water is added again, the mixture stirred vigorously and the precipitate allowed to settle, after which the wash water is siphoned off. Water is again added and casein is dissolved by adding, for each liter of milk used, 1 liter of dilute NH40H (6 c.c. of strong reagent to 1000 c.c.). When the solution is complete, the whole is filtered through a thick layer of absorbent cotton. The casein is then precipitated again with dilute acetic acid; the precipitate is allowed to settle and is then washed, redissolved in dilute NH40H, and filtered, the process of precipitation, wash- ing, dissolving, etc., being repeated not less than four times. Finally an excess of strong NH40H (10 c.c.) is added and then 20 c.c. of saturated solution of ammonium oxalate. The mixture is allowed to stand 12 hours or more. Calcium is precipitated as oxalate in very finely divided condi- tion, too fine to permit its satisfactory removal by ordinary means of filtration. Better aggregation of the precipitate can, however, be effected by means of centrifugal force. The centrifuge tubeful of mixture is then filtered through double thickness of filter paper. The filtered solution is then treated with dilute HC1 (10 c.c. HC1, sp. gr. 1.20 diluted to 1000 c.c.) until the casein is precipi- tated. The precipitate is washed with distilled water until free from chloride and is then placed on a hardened filter paper in a Buchner funnel; as much water as possible is now removed by suction. The mass is next transferred to a large mortar and thoroughly SPECIAL PROCEDURES FOR GASTROINTESTINAL CASES 121 triturated with 95 per cent alcohol. The alcohol is then removed by suction on a Buchner funnel and the casein is then again placed in a mortar and triturated with absolute alcohol. Most of the alcohol is removed and the casein treated twice with ether in a mortar by trituration, the ether being removed each time by means of suction of a Buchner funnel. The material is then placed in a large evaporating dish and spread out in a layer as thin as possible; it is allowed to stand twelve hours or more in a warm place. The material is finally ground in a mortar until particles pass a 40-mesh sieve, and is then dried for two days over H2SO4 in a dessicator under dimin- ished pressure. The ash contents on specimens were 0.10, 0.09, and 0.06 per cent. Specimens were insoluble in water, in 50 per cent alcohol, and in 5 per cent NaCl. When 1 gm. of these casein preparations was treated with 10 c.c. N/10 NH40H, NaOH, or KOH, and 90 c.c. of water, a clear solution was obtained, the casein being dissolved completely. When to this solution a minute amount of a solution of a salt of barium, strontium or calcium was added there developed promptly the opalescent appearance characteristic of casein solutions under such condition. Casein prepared in the manner described was analyzed with the following results: Moisture 1.099. In the dry substance: Ash 0.06; C. 53.50; N. 7.13; N. 15.80; P. 0.71; So. 72; O (by difference) 22.08 per cent. Casein Solution.-Neutralize 1 gm. (accurate weight) of soluble casein with 4 c.c. of tenth normal sodium hydroxide solution and add 100 c.c. of the 0.2 molar phosphate mixture. By the aid of heat and vigorous rotation of the flask dissolve the casein com- pletely. This is done by adding the phosphate mixture to the casein in a dry flask and rotating quickly to prevent the formation of a doughy, relatively insoluble mass. The sodium hydroxide solution is then added and, continuing the rotation, the flask is heated over a small flame to 57° C., removed from the flame and rotated until the casein has dissolved. Twenty-five Per Cent Metaphosphoric Acid Solution.-(Folin and Denis: Jour. Biol. Chem., 1916, xxvi, 491.) The preparation of metaphosphoric acid usually obtained on the market should be 122 METHODS IN MEDICINE fused in a graphite mortar until the white fumes of phosphorus pentoxid begin to appear. The fused material can be cooled con- veniently by pouring into a clean pie-pan floating on cold water. Metaphosphoric acid so fused will remain a potent protein pre- cipitant if kept in tightly stoppered bottles. The 25 per cent solution can be made quickly by triturating the desired amounts of metaphosphoric acid and water in a mortar. Digestion Mixture and Nessler's Solution are prepared as di- rected by Folin and Wu: (Jour. Biol. Chem., 1919, xxxviii, 81) the Standard Ammonium Sulphate Solution as directed by Folin and Denis (Jour. Biol. Chem., 1916, xxvi, 491). 0.5 mg. of ammonia nitrogen and 1 c.c. of phosphoric-sulphuric acid are mixed, diluted, neutralized, cooled, and nesslerized as in the case of the unknown (in a 100 c.c. volumetric flask). Method.-The duodenal contents are centrifuged until a clear or but slightly turbid supernatant fluid is obtained. The latter is decanted into a clean tube. In a 50 c.c. volumetric flask place 1 c.c. of this fluid and make up to the mark with 0.2 molar phos- phate mixture solution of pH 8.4, and mix thoroughly. Into test tubes (100 x 10 mm.) place 9 c.c. of the casein solution. Heat in the water-bath at 40° C. for five minutes. Then add 1 c.c. of the diluted duodenal contents, mix and incubate in the water- bath for thirty minutes at 40° C. Now add 2 c.c. of a freshly prepared 25 per cent solution of metaphosphoric acid, mix thor- oughly and filter. A perfectly clear, colorless filtrate should be obtained. One c.c. of this filtrate is added to 1 c.c. of the digestion mixture in a Pyrex glass tube (200 x 25 mm.), a quartz pebble is added and digestion is carried out according to the micro-Kjeldahl method of Folin and Wu for nonprotein nitrogen in the blood. In brief, the method consists of boiling off the water and, when the white fumes of sulphuric acid begin to develop, the mouth of the tube is covered with a watch glass. Digestion is continued for from thirty to sixty seconds after the last trace of the brown color has disappeared. The tube is then allowed to cool for from sixty to seventy seconds, and from 5 to 10 c.c. of water are quickly added. The contents of the tube are cooled, made up to the 35 c.c. mark with water and 15 c.c. of Nessler's solution added. The nesslerized solution is centrifugalized to get rid of the sediment (the sediment must be pure white and not discolored by the precipitation of any SPECIAL PROCEDURES FOR GASTROINTESTINAL CASES 123 of the coloring matter), and compared with standard ammonium sulphate solutions (usually containing 0.25 and 0.5 gm. nitrogen). These are prepared by placing 2 c.c. of the digestion mixture in a 100 c.c. volumetric flask, adding 5 or 10 c.c. of standard ammonium sulphate solution, about 60 c.c. of water, 30 c.c. of Nessler's solu- tion and making up to the mark with water. Two controls are probably necessary for safety: (1) 1 c.c. of the diluted duodenal contents and 9 c.c. of the 0.12 molar phosphate mixture solution; and (2) 9 c.c. of the casein solution plus 1 c.c. of the phosphate mixture. In our experience neither of the con- trols has developed more than a trace of yellow color after diges- tion and nesslerization. Estimation of Lipolytic Activity of Duodenal Contents Reagents Tenth Normal Sodium Hydroxide.-Made up in 95 per cent ethyl alcohol. Fat Emulsion is prepared by making a suspension of four parts of cotton seed oil, one part of powdered gum acacia and two parts of water according to the method given in the U. S. Pharmacopeia. Four hundred c.c. of this suspension are mixed with 600 c.c. of water and emulsified by running through a fat emulsifying machine at from 300 to 350 kilos pressure per square cm. The emulsion may be put in pint milk bottles, hermetically sealed with patented metal caps and sterilized at 15 pounds pressure in the autoclave. Emulsion thus prepared keeps indefinitely. For use in digestion experiments the fat emulsion is mixed with an equal volume of the 0.33 molar phosphate mixture solution given below. Phosphate Mixture Solution.-One-third (0.33) molar phosphate mixture solution of pH 8.4 is prepared as follows: 53.4425 gm. of disodium phosphate (Na2HPO4.2TLO) are dissolved in exactly one liter of water, 20.4255 gm. of potassium acid phosphate (KH2P04) are dissolved in exactly 500 c.c. of water. Twenty c.c. of the potas- sium acid phosphate solution are added to 980 c.c. of the disodium phosphate solution which gives pH 8.4. Method.-One c.c. of the centrifugalized duodenal contents are diluted to 50 c.c. with the 0.33 molar phosphate mixture solution. 124 METHODS IN MEDICINE Nine c.c. of the fat emulsion phosphate mixture solution are pi- petted into test tubes (100 x 10 mm.). The tubes are incubated in the water-bath at 40° C. for five minutes; then 1 c.c. of the diluted duodenal contents is added, the tubes shaken and again incubated for one hour at 40° C. Then the contents of the tubes are at once poured into small Erlenmeyer flasks (about 150 c.c. capacity), the tubes rinsed with about 20 c.c. of 95 per cent ethyl alcohol and the rinsings added to the flasks (the ethyl alcohol has first been neutralized with tenth normal sodium hydroxide after adding phenolphthalein and titrating cold). Ten drops of a 1 per cent phenolphthalein solution are added to each flask. The degree of acidity developed, due to the formation of fatty acids, is deter- mined by titrating with tenth normal alcoholic sodium hydroxide, with the contents of the flask boiling hot. A control tube containing 9 c.c. of the fat emulsion phosphate mixture solution and one c.c. of the 0.33 molar phosphate mixture solution is to be used. Under the experimental conditions outlined different samples from the same specimen of duodenal contents will develop acidities checking within 0.1 c.c. of tenth normal sodium hydroxide. Estimation of Amylolytic Activity of Duodenal Contents Reagents Molybdic acid reagent, copper sulphate mixture and the stock glucose solutions are prepared according to the directions given in the revised method of Folin and Wu (Jour. Biol. Chem., 1920, xli, 367) for the estimation of sugar in the blood. The dilutions of the stock glucose solutions, which are to be used as standards, are made up in 0.1 molar phosphate solution of pH8.4. Phosphate Mixture Solution.-Two-tenths molar phosphate mix- ture of pH8.4. This is prepared in the manner already described (proteolytic enzyme estimation). Starch-Phosphate Mixture Solution.-Four grams of soluble starch are completely dissolved in 100 c.c. of hot distilled water, cooled and diluted with an equal volume of the 0.2 molar phos- phate mixture solution of pH8.4. Method.-In a 25 c.c. volumetric flask place 1 c.c. of the centri- SPECIAL PROCEDURES FOR GASTROINTESTINAL CASES 125 fuged duodenal contents, make up to the mark with the 0.2 molar phosphate mixture of pH8.4 and mix thoroughly. In test tubes (100 x 10 mm.) place 9 c.c. of the starch-phosphate mixture solution. Heat in the water-bath at 40° C. for five minutes. Then add 1 c.c. of the diluted duodenal contents, mix and incubate in the water-bath at 40° C. for 30 minutes. Incubation may be carried out for a period of one hour instead of the thirty min- ute period, if it is desirable to obtain a larger amount of starch digestion. In the meantime place 2 c.c. of the copper solution into the special blood sugar tubes of Folin and Wu (Jour. Biol. Chem., 1918, xxxviii, 81). After completion of the 30 minute incubation period, pipette immediately 2 c.c. of the digested starch solution into the prepared blood sugar tubes, rotate the contents gently and place in boiling water for six minutes. Then cool, add 2 c.c. of the molybdate solution, make up to the mark, mix and compare the color produced with standard glucose solutions. These are pre- pared as follows: 2 c.c. of the standard glucose solution are added to 2 c.c. of the copper solution in the special blood sugar tubes, boiled along with the specimens for analysis and further treated the same as these specimens. A control of 1 c.c. of the diluted duodenal contents and 9 c.c. of the starch-phosphate mixture solution should be used; 2 c.c. being immediately pipetted into the copper sulphate mixture to stop the action of amylolytic enzyme present. Only .preparations of soluble starch containing very small amounts of sugar should be used. It is convenient to determine the sugar content of a bulk of starch and then to use the preparation for all determinations. In this way the quantity of sugar present in the starch-phosphate mixture solution outlined in the method can be calculated. The amount present is to be deducted from the result obtained after the completion of digestion experiment. Using the method outlined above, repeated estimations of the amylolytic activity of the same specimen of duodenal contents has always given the same result; that is, within the limits of experi- mental error. Reference: McClure, C. W., Wetmore, A. S., Reynolds, L.: Arch. Int. Med., 1921, xxvii, 706. 126 METHODS IN MEDICINE GALL BLADDER AND BILIARY TRACT DIAGNOSTIC PROCEDURE 1. Examination is begun in the fasting stomach state. Aseptic technic is used. 2. Mouth rinsed thoroughly with any good antiseptic solution: 1/ Potass. Permanganate 100 mg. Aquae distilat. (sterile) 66 c.c. Follow by Zinc chloride solution (weak). 3. Sterile duodenal tube with metal tip is passed. Fasting gastric contents aspirated under sterile precautions and examined com- pletely. Measured. Grossly observed as to color, odor, consistency, mucus, etc. Cultivated. Studied chemically for acidities, bile and occult blood. Microscopically examined for endogenous and exogenous epithe- lium, polymorphonuclears and their state of preservation, general amount and morphology of bacterial Hora. 4. After the stomach is thoroughly rinsed with sterile water, the patient is given a glass of sterile water to drink while slowly swal- lowing the tube to the duodenal point (70-90 cm.) and while lying on the right side with a pillow or sand bag elevating the hips. 5. The tube usually passes into duodenum within 15 to 45 min- utes. Its presence there is determined by the duodenal "tug," the character of aspirated fluid, and the failure to recover im- mediately material taken by mouth, as water, etc. Note: If a vagotonic state or a pylorospasm is encountered give atropine sulphate gr. %0 "H" or prepare the patient for days by regular moderate doses of belladonna or benzyl benzoate. 6. When the tube is in the duodenum, a barrel full (20-3'0 c.c.) air is introduced to balloon out the duodenal walls. A connection is then made with the first sterile aspirating vacuum bottle and gentle aspiration is begun and the contents withdrawn. The bottle is then detached and with its contents set aside for bacteriologic, cytologic and chemical examination. 7. Thirty to 50 c.c. of sterile 33 per cent sat. sol. of magnesium sulphate are introduced with a sterile syringe or a gravity ap- SPECIAL PROCEDURES FOR GASTROINTESTINAL CASES 127 paratus. The tubing is then connected up to the second sterile aspirating bottle and gentle aspiration started. Within 2 to 10 minutes bile begins to be recovered. When the color deepens to a pronounced yellow, the material (Mg2SO4 plus bile) already col- lected in the second bottle is decanted into a sterile glass container. If the first douching is unsuccessful in relaxing Oddi's muscle, douching is repeated with 30 c.c. at half hour intervals. 8. The second bottle is reattached and biliary drainage con- tinued until 10 c.c. to 20 c.c. are obtained in one to three minutes, and a sudden transition appears (seen first in the glass window in the tube) and the bile becomes darker and more viscid and more concentrated, (a molasses yellow color). At this point the second bottle is detached with its contents, which are considered to be bile from the ducts. 9. The third bottle is attached and aspiration is continued until all this darker bile has been collected (30 to 100 c.c.) and a yellow, thinner, transparent bile appears. The third bottle thus contains the bile, considered to be from the gall bladder. 10. The fourth bottle is then attached and the slowly and inter- mittently flowing liver bile is collected. The specimens are all examined bacteriologically, microscopi- cally and chemically. For descriptions of normal findings and findings in the differ- ential diagnosis of duodenitis, choledochitis, cholecystitis, chole- lithiasis and hepatitis see abstracts below and the original articles. Reference: Lyon, B. B. Vincent, Jour. Am. Med. Assn., Sept. 27, 1919, Ixxiii, 980. Einhorn after studying the action of various salts and other sub- stances on the liver after their introduction into the duodenum concluded that Lyon's assumption of the different sources of the bile, as judged by the color did not seem to be correct. Since the magnesium sulphate and other liver stimulants increase the flow of the bile from the liver and drive it directly and promptly into the duodenum, there will be, according to Einhorn, following the introduction of these substances, a bile product from the liver di- rect, containing very little if any bile from the gall bladder. On the other hand in the fasting condition and without any previous stimulation, aspiration succeeds in obtaining what little bile there is in the duodenum from the liver and gall bladder and there seems 128 METHODS IN MEDICINE to be more chance for the appearance of some gall bladder bile when the flow from the liver is not extensive. Therefore this fast- ing aspiration seems to provide the best conditions for the exami- nation of the bile in gall bladder lesions and Einhorn claims to have found many more valuable hints regarding gall bladder lesions from the natural fasting bile than from the bile after magnesium sulphate stimulation. With jaundice especially of the catarrhal type when no bile is found in the fasting duodenal contents, a liver stimulant as mag- nesium sulphate is often successful in pushing bile through into the duodenum. Einhorn considers the introduction of magnesium sulphate, peptone or glucose into the fasting duodenum a diag- nostic aid in all cases of .chronic jaundice. Reference: Einhorn, Max: New York Med. Jour., Feb. 19, 1921, cxiii, 313 and Sept. 7, 1921, cxiv, 262. Smithies, Karshner and Oleson after a study of a long series of cases defend the method and conclusions of Lyon in considerable detail and attempt to meet the objections of other recent investi- gators. They had but slight modifications to suggest. Elaborate attempts toward rendering the alimentary tract sterile did not seem worth while as similar results were obtained in patients studied only after an absolute twelve hour fast with stomach and duodenum food free. The nasal and oral passages having been cleansed the night previous to the test day by antiseptic gargles, nasal douches and the brushing and scrubbing of the teeth, and the ingestion of copi- ous amounts of cold water, the teeth and mouth alone are cleaned on the morning of the test, and a sterile duodenal tube is introduced. The patient is kept in a right modified Sims' position with the thighs well flexed on the trunk, in pleasant surroundings in an at- mosphere of leisurely quiet and accommodation. Spontaneous drainage is thought by these investigators to give unreliable results. One, two or three instillations of 15 per cent MgSO4 solution were used. Satisfactory response was obtained in less than two hours in only one case; between two and four hours were required by 67; from four to six hours by 291 and longer than six hours by 188. The A.B.C. sequence of bile flow was considered practically feasible, after duodenal excitation by MgS04 in 95 per cent of subjects with- out alimentary or biliary tract symptom anomalies. SPECIAL PROCEDURES FOR GASTROINTESTINAL CASES 129 The indications of gall tract disease as revealed by metapyloric drainage were enumerated as follows: 1. No bile in the duodenum after repeated stimulation. 2. More than 25 c.c. of common duct bile with abnormal sediments of blood, cholesterin, pigment, calculi, epithelium and nuclei. 3. No gall bladder, (B) bile after repeated stimulation. 4. Less than 20 c.c. or more than 75 c.c. of gall bladder (B) bile or abnormal sediment in the (B) specimen. The therapeutic uses of nonsurgical biliary tract drainage were also enumerated. Reference: Smithies, Frank, Karshner, C. F., and Oleson, B. B.: Jour. Am. Med. Assn., Dec. 24, 1921, Ixxvii, 2036. Hollander vigorously defends the Meltzer-Lyon procedure. He considers the criticisms of Einhorn, Bassler, Crohn, Dunn and Con- nell as incorrect deductions from observations, rather than true objections to the fundamental principles of the reaction. He cor- relates the "criticisms" with the known facts of experimental phy- siology and pathology. He reviews the literature quite completely. After considerable experience he advocates certain simplifications. The test should be begun after a twelve-hour fasting period. The preliminary washings and sterilizations of the stomach were omitted. After obtaining a specimen of fasting gastric juice, the duodenal tube was pushed along until the bulb was in the duode- num, which usually required one-half to two hours. The failure to recover swallowed water or less than half of a volume injected through the tube, together with the appearance and reaction of the bile should give a fairly accurate idea of the position of the metal tip of the tube. After removing a sample of fasting duodenal contents, the duodenum is lavaged with 90 c.c. of water at body temperature for washing away any superficial mucus; the gall bladder response is stimulated by the injection of 60 c.c. of 5 pei' cent Armour's peptone. Response is stimulated by the injection of 60 c.c. of 5 per cent Armour's peptone. Response may be slow and if so, 10 per cent may be more effective. Sometimes a half hour may elapse before the bile appears. Following the reaction to peptone, 75 c.c. of 33 per cent mag- nesium sulphate is injected to determine the degree of duodenitis and to re-stimulate gall bladder discharge. A second and even a third injection of 25 c.c. of 33 per cent magnesium sulphate is given 130 METHODS IN MEDICINE if no response follows the previous injections. The entire pro- cedure must be carefully watched to guard against dislocation of the duodenal tip. Examinations (especially microscopical ones) should be made on the specimens immediately,-that is, before clouding takes place. Diagnostic Findings.-Note the physical characteristics as to quantity, color, transparency or turbidity, viscosity, manner of dis- charge, flocculi, sand, microscopical findings of specimens studied with oil immersion as to epithelium, leucocytes, erythrocytes, bac- teria, crystals, mucus, and inflammatory debris; chemical reaction and alkalinity per cent with methyl orange as the indicator. In normal subjects (if the sphincter is closed), 10 to 20 c.c. of clear golden-yellow bile, "A" bile, is followed after one to three minutes, by 30 to 90 c.c. of syrupy, darker, transpar- ent amber bile, "B" bile, and then a varying quantity of light clear golden-yellow bile, "C" bile. Microscopically, there are present occasional epithelial cells, leucocytes, bacteria, scattered bile crystals and traces of mucus from the duodenum or bile. Changes from the normal findings indicate malfunction or disease. The diagnosis may be made by the correlation of the following observations: 1. Failure to obtain bile after successive stimulations indicates occlusion of the common duct. 2. The volume of "A" bile is dependent on the time interval between the injection and the gall bladder response, as well as on the degree of dilatation of the common duct. 3. Failure to obtain "B" bile in repeated tests is indicative of an organic condition which is interfering with the function of the gall-bladder. This finding, in conjunction with the clinical picture, is a distinct indication for surgical intervention. 4. Sand or agminated crystals is evidence of a tendency toward or of the actual presence of stones. 5. Swarming or colonizing bacteria indicate active infection. 6. Increased number of or massed leucocytes are indicative of an acute or subacute inflammatory reaction. The use of 2 per cent acetic acid brings out the nuclei more clearly. 7. Darker colors of "B" bile, clear, to slightly turbid, (deeper shades of amber to tarry black), with sluggish or intermittent dis- SPECIAL PROCEDURES FOR GASTROINTESTINAL CASES 131 charge, yielding more than 90 c.c. or less than 20 c.c., are indicative of various degrees of gall bladder stasis. 8. Columnar cells, especially tall columnar cells, usually degen- erating, deeply bile stained, and in fan or rosette formation, when present only in the "B" fraction, represent catarrhal desquamation from the gall bladder. Frequently intensively bile-stained detritus is also present. 9. Mild gall bladder colic soon (and in some cases a few hours later), after the injections, indicates an inflammatory condition of the gall bladder. 10. Whipple's results show that contaminations from the mouth and stomach are unavoidable in many cases, even with the most careful technic. There were conflicting findings in about 50 per cent of his cases. From his results it may be that when gross in- fection (direct microscopic evidence) is absent, cultural methods are not reliable. Reference: Hollander, Edw.: Am. Jour. Med. Sc., April, 1923, clxv, 497. DUODENAL PIGMENT ESTIMATION A duodenal method for the estimation of hemolysis has been advo- cated by Schneider. Quantitative estimations of the pigment con- centration in samples of duodenal contents are made. The rate of biliary flow is not constant and the exact rate cannot be estimated. The escape of the duodenal contents into the jejunum cannot be prevented or calculated. The quantitative methods for bilirubin, urobilinogen, and urobilin are not exact, consequently the results of the test do not seem to be exact or absolutely reliable. If the total 24-hour amount of bile could be recovered, the method would be considerably improved. The red blood cell destruction may be considered as having an index in the amounts of urobilinogen and urobilin in the 24-hour stool and urine output. The duodenal tube is inserted in the usual way, after a twelve- hour fast, and the usual precautions are taken to be sure that the tip is in place. The fasting duodenal contents are removed, meas- ured, and examined grossly, microscopically, chemically, and colorimetrically. Grossly, the depth of color is of importance. According to Schneider four distinct shades or gradations are found. The choco- 132 METHODS IN MEDICINE late-yellow is characteristic of distinct pleochromia. The normal canary-yellow bile may be clear bnt may be clonded dne to richness in bile acids and admixture with hydrochloric acid, and should not be regarded as turbid from mucus. The light yellow is significant of a duodenal secretion poor in bile pigment, an oligochromia. A colorless secretion is due to absence of pigments, an achromia. Bilirubin Estimation.-The amount of bilirubin in a given sam- ple of duodenal contents is estimated roughly by taking 10 c.c. of the duodenal contents and adding 10 c.c. of an alkaline solution of calcium chloride. After vigorous shaking, the mixture is filtered. The precipitate is dissolved under gentle heat in 10 c.c. of acid alcohol and the resulting green solution is concentrated to a given volume. By colorimetric comparison with a standard bilirubin acid alcohol solution, the quantity can be estimated. Huppert-Cole Method (Cole: Practical Phys. Chem., 1920, ed. 6, p. 268). Boil 10 c.c. of the duodenal fluid in a test tube. Add two drops of a saturated solution of magnesium sulphate, then add a 10 per cent solution of barium chloride drop by drop, boiling be- tween each addition. Continue to add barium chloride until no further precipitate is obtained. Allow the tube to stand a minute. Pour off the supernatant fluid as cleanly as possible or use centri- fugalization. To the precipitate add 5 c.c. of 97 per cent alcohol, two drops of strong H,SO4 and two drops of a 5 per cent aqueous solution of potassium chlorate. Boil for half a minute and allow the barium sulphate to settle. Bile pigments are indicated by the alcoholic solution being colored a greenish blue. Pour off alcoholic solution from barium sulphate into a dry tube and compare colori- metrically with a standard alcoholic solution. Add 5 or 10 c.c. of chloroform, mix thoroughly. To this add an equal volume of water, invert a few times. Allow chloroform containing the blu- ish pigment to separate and compare with a standard chloroform bilirubin solution. The method of v. d. Bergh (Bioehem. Ztchr., 1916, Ixxvii, 90) for the estimation of bilirubin in the blood plasma has been applied to the quantitative estimation of bilirubin in the bile, etc. The method consisted in adding to a volume of serum a volume of 96 per cent alcohol. The precipitated albumin is removed by centri- fuging the specimen and pouring off the supernatant clear alcoholic solution. Ehrlich's diazo reaction is applied to the alcoholic soln- 133 SPECIAL PROCEDURES FOR GASTROINTESTINAL CASES tion and the resulting red violet color compared with that of a standard solution in an Autenrieth's colorimeter (Hellige). Meulengracht (Deutsch. Arch. f. klin. Med., 1921, cxxxvii, 3'9) objects to the above method on the basis of its being inaccurate due to the loss of bilirubin during the precipitation process. He proposes a most simple substitute method for the estimation of the bilirubin content of blood plasma, which with modification might be applied to other fluids. Technic.-Three c.c. of blood are removed from an arm vein through a sharp, absolutely clean and dry needle and placed in a small clean test tube (as used for the Wassermann) containing 2 drops of 3 per cent sodium oxalate solution to prevent coagulation. The solution is mixed by turning gently for a few times and allowed to stand for 12 to 24 hours to allow the blood cells to settle out, if in a hurry the solution may be centrifuged. An apparatus similar to the Gowers-Sahli instrument is employed. With a grad- uated pipette % c.c. of the oxalated plasma is placed in the "unknown" tube, which is graduated in % c c- The unknown plasma is diluted with physiologic saline solution until it equals the standard solution in color. The height of the diluted fluid gives the dilution number. In severely jaundiced cases the plasma must be diluted before being put to the test, and the results multiplied accordingly. The standard solution is made up of inorganic salts and is per- manent. It consists of 0.05 parts of potassium bichromate in 500 parts of distilled water, to which 2 drops of sulphuric acid, have been added. Urobilinogen and Urobilin Estimation.-The amount of uro- bilinogen and urobilin is determined by mixing 10 c.c. of duodenal contents with 10 c.c. of Schlesinger's solution (saturated alcoholic zinc acetate or zinc chloride solution) shaking the whole thoroughly and then allowing it to filter. The filtrate should be slightly alkaline; if the reaction is not so, a drop or two of dilute ammonia solution is added. The filtrate will in the presence of urobilin show a more or less pronounced green opalescence. To 10 c.c. of this filtrate is added 1 c.c. of Ehrlich's benzaldehyde solution (Paradimethylaminobenzaldehyd, 2 gm.; hydrochloric acid, 15 c.c.; distilled water, 15 c.c.). In the presence of urobilinogen a red color will develop. This is allowed to stand in a dark place for 134 METHODS IN MEDICINE fifteen minutes, when it is subjected to a spectroscope study for a value of both urobilinogen and urobilin. The acid character of Ehrlich's solution enhances the absorption bands of both these pigments many fold, the urobilinogen band being a very dense narrow one in the yellow and the urobilin a wide one covering all of the blue into the green, the acid shifting the latter to the blue side. The above solution is read in a graduate and dilutions made with 95 per cent alcohol, until a point is reached for each pigment where the absorption will have disappeared at a fixed median position of the aperture, to again reappear with two revolutions of the aperture towards closure (Kirchoff and Bunsen, large model spectroscope is most satisfactory). The number of dilutions re- quired for each element multiplied by twenty (5 c.c. of the original duodenal contents) will be the dilution value per 100 c.c. Follow- ing the basis used by Wilbur and Addis, the value has been re- duced to the scale 1,000 c.c. In developing this method as applied to the duodenal contents it would appear that bilirubin being so concentrated would present a practical difficulty in that it gives a diffuse absorption of the spectrum. Wilbur and Addis, working with the products of gall bladders, fistulae, etc., made use of fullers' earth (kaolin) to re- move bilirubin. It has been found that it does so, but that it also removes especially urobilin. If the original 10 c.c. are well shaken with Schlesinger's solution before filtering, practically all of the bilirubin is removed, the retained quantity causing no error or inconvenience, owing to the fact that the end stages are read in a highly diluted medium where any slight diffuse absorption of the spectrum no longer operates. References: Schneider, J. P.: Arch. Int. Med., 1916, xvii, 32. Giffen, H. Z., Sanford, A. H., and Szlapka, T. J.: Am. Jour. Med. Sc., 1918, civ, 592. Hansmann, G. H., and Howard, G. P.: Jour. A. M. A., 1919, Ixxiii, 1262. Wilbur, R. L., and Addis, T.: Arch. Int. Med., 1914, xiii, 235. The Phenoltetrachlorphthalein Test LIVER FUNCTION TESTS Preparation of the Stable Solution of the Compound.-Two and one-half grams of Phenoltetrachlorphthalein are placed in a 200 c.c. flask with 5 c.c. of 2' N sodium hydroxide and 45 c.c. triply dis- tilled water. SPECIAL PROCEDURES FOR GASTROINTESTINAL CASES 135 Boil 20 minutes under a reflux condenser and then filter into a 100 c.c. flask, the resulting aqueous solution is the disodium salt of phenoltetrachlorphthalein, which is an intense purplish red and decidedly unstable compound. This instability is due to the fact that the alkali of the salt tends to combine either with the silicate of the glass or the carbon dioxide of the air. To overcome these difficulties, ampules containing as little silicate as possible are placed in cleaning fluid for one hour and then rinsed six times with fresh tap water. Then they are placed on an ampule washer and washed until entirely free from cleaning fluid. Then they are washed with three changes of distilled water and allowed to dry. They are plugged with absorbent cotton and placed in a hot air sterilizer at 220° C. for one and one-half hours. One and one-half c.c. of the solution representing 75 mg. of "tetrachlor," are poured into these ampules aseptically and sealed hermetically. The solution thus prepared is stable for at least eight months. Method of Procedure.-The duodenal tube is passed into the fasting stomach and all the gastric contents are withdrawn. The tube is then allowed to pass into the duodenum, aided by posture, swallows of water by mouth, and occasional partial withdrawal of the tube. The ingestion of 500 c.c. cool water is necessary to obtain a constant drip of duodenal contents during the test. All the ordinary means of demonstrating the presence of the end of the tube in the duodenum are employed except the use of milk or colored fluids which would confuse the test reaction. The patient is placed on his right side with his hips elevated: The thin watery or viscid fluid duodenal contents are siphoned off in a slow intermittent drip. With a tube of 4.5 c.c. capacity it requires from two to five minutes for a given drop to travel from the duodenal tip to the external end of the tube. A con- tinuous drip of 60 to 80 drops a minute, and then bile stained duodenal fluid, is obtained for thirty to forty-five minutes which gives plenty of time to carry out the test. At about two minute intervals there is an expulsion of thicker, darker bile stained con- tents. With an established constant drip, a needle only is inserted into a prominent vein and a tuberculin syringe containing 1 c.c. of the solution which represents 50 mg. of the "tetrachlor," is con- 136 METHODS IN MEDICINE nected, and the complete content of dye slowly injected and the time noted. The drip is caught in a white porcelain dish containing a 40 per cent NaOH solution, a clean dish with fresh alkali is substituted every two minutes. The first appearance of the dye is indicated by a faint purplish red ring at the point of contact of the duodenal fluid and the alkali. The color change becomes more intense with time until a maximum is reached, which is considered the end point. The average normal time for the appearance of the dye was 17 minutes. Definite delay to 20 minutes and over, strongly suggests hepatic involvement. If the delay is for more than 30 minutes more water must be given by mouth to maintain the drip longer. Quantitative estimations of amounts secreted in a given time are unreliable because of the incalculable leakage of duodenal contents into the intestine below. References: McNeil, H. L.: Jour. Lab. and Clin. Med., August, 1916, i, 822. Aaron, A. A., Beck, E. C. and Schneider, H. C.: Jour. Am. Med. Assn., 1921, Ixxvii, 1631. Rosenthal, S. M.: Jour. Am. Med. Assn., Dec., 1922, Ixxix, 2151. Colorimetric Determination of Retention of Phenoltetrachlor- phthalein in the Blood Plasma as a Test of Hepatic Function The above described stable "tetrachlor" solution containing 25 mg. per c.c. is a satisfactory preparation for use in this test. The test dose is calculated on the basis of 5 mg. of phenoltetrachlor- phthalein per kilogram (2.2 lbs.) of body weight. The exact num- ber of c.c. of the sterile stable stock solution containing the cal- culated dose is drawn up with aseptic technic into a sterile 30 c.c. Luer syringe. A short connection of sterile rubber tubing with a clamp or a three-way valve is then attached to the syringe and sterile physiologic salt solution is drawn up to the 25 c.c. mark. With a dry needle of moderate bore, a superficial vein of the fore- arm is entered and 10 c.c. of blood collected in a clean dry test tube. The saline solution of the dye in the syringe, previously prepared as above described, is connected up with the venepuncture needle and moderately slowly injected. The time of completion of the injection is noted. The syringe is disconnected and refilled with physiologic saline and this in turn is injected through the vene- puncture needle in order to wash the apparatus and the vein wall SPECIAL PROCEDURES FOR GASTROINTESTINAL CASES 137 free of the dye. Blood in about 5 c.c. amounts is then removed from a superficial vein of the other, or untouched, arm, fifteen minutes, one hour, and, in some cases, again twenty-four hours after injection. The needle and syringe used for the withdrawal of the blood sample must be clean and thoroughly rinsed and moist- ened with clean normal saline which has not been in contact with the dye. Anticoagulants are avoided because occasionally a con- fusing hemolysis is caused. The blood specimens are allowed to cool for an hour and coagu- late, the clot is loosened and the specimen then centrifuged at high speed. The serum of each specimen is pipetted off and placed in 1 c.c. amounts in separate small test tubes of uniform size. One drop of 5 per cent sodium hydroxide is added to each tube and colori- metric comparisons are made with the plasma percentage standard, made up according to the following scheme. The 100 per cent standard is made up by adding 10 mg. of phenoltetrachlorphthalein to 100 c.c. of water, since according to Rosenthal 10 mg. per 100 c.c. is the approximate amount that would be found in the blood plasma after the injection of 5 mg. per kilo- gram of body weight if none were eliminated at all. This 100 per cent standard solution can then be diluted, making a series 100 per cent, 80 per cent, 60 per cent, 40 per cent, 20 per cent, and 10 per cent and 0.2 c.c. of each of these added to tubes of uniform size containing 0.6 c.c. of the patient's control serum of blood, taken before the dye was injected, would give respectively 25 per cent, 20 per cent, 15 per cent, 10 per cent, 5 per cent, and 2.5 per cent as a series of standards. A drop of 15 per cent sodium hy- droxide is added to each to bring out the full color. The one c.c. of alkalinized serum in which the amount of dye is to be determined is matched with the standards in good daylight. The direct comparisons are made with the naked eye. The per- centages thus derived indicate approximately what part of the in- jected amount is still present in the blood stream. The milligrams of dye per 100 c.c. of serum can be determined by dividing the per- centage by 10, the number of milligrams used in 100 c.c. of the standard. Normally, the amount of "tetrachlor" (5 mg. per kilogram) is rapidly removed from the blood stream and eliminated, so that at the end of fifteen minutes after injection only 2 to 5 per cent is 138 METHODS IN MEDICINE detectable in the blood serum and at the end of one hour none is detectable in the alkalinized serum. In about half of the cases, however, a faint ring test may be secured. The ring test is a sensi- tive qualitative test which consists in layering a specimen of serum acidified with 3 per cent HC1 over a 5 per cent sodium hydrate solution. This permits the utilization of very small amounts of plasma, such as might be obtained by pricking the ear or the finger- tip and can be used to follow the process after the hour period to determine the time required for the total disappearance of the dye from the blood stream. Reference: Rosenthal, S. M.: Jour. Amer. Med. Assoc., Dec., 1922, Ixxix, 2151. The Bile Content of the Blood Plasma as a Differential Test of the Types of Jaundice There is a physical difference in the bile pigment in the plasma in obstructive jaundice due to common duct stone, pancreatic or hepatic carcinoma or cirrhosis and hemolytic, acholuric functional or toxic jaundice due to hemolysis, catarrhal jaundice, or infec- tions as pneumonia, typhoid fever, etc. This physical difference, Blankenhorn suggests, is one of degree of staining of the plasma proteins and varies according to the concentration of the stain and the length of time that the plasma protein is exposed to the stain. Blankenhorn used oxalated plasma free of products of hemolysis and applied to this Gmelin's test, colorimetric inspections following dilutions, dialysis, coagulation and alcohol extraction. The dialy- sate was studied with Gmelin's test, colorimetric inspection, and Pettenkofer's test with spectroscopic examination. The urobilino- gen and urobilin tests were also applied. In Gmelin's test for bilirubin in the blood plasma, the nitric acid is pipetted under the plasma in a test tube. A white coagulum and a yellow granular zone of contact appear promptly. The width of the white zone remains fairly constant as the coagulum forms at the upper border at about the same rate that it dissolves at the lower border. The zone therefore ascends through the plasma. Within the white coagulum there appears a more or less broad ring or zone of a distinct blue green color depending on the concentra- tion of the bilirubin in the plasma. When the pigment is present in small amounts only, the blue green color may not appear for SPECIAL PROCEDURES FOR GASTROINTESTINAL CASES 139 half an hour. The blue green ring always remains in the same position in the white coagulum as long as there is any of the latter. The test is sensitive to approximately one part of bilirubin in thirty thousand parts of plasma. However, a yellow stain remains just perceptible in a 1 cm. column of plasma in a dilution of 1 to 250,000 and so colorimetric inspection is much more sensitive than the nitric acid test. In using the staining of the plasma as a measure of the bilirubin content, the amount is expressed by the dilution required to diminish the staining to a point where it is just per- ceptible in a cm. column. Distilled water slightly alkalinized by a drop of ammonium hydroxide is used as a diluent. Comparison is made with a 1 cm. column of distilled water with both tubes im- mersed in watei' in an evaporating dish. The method of Hooper and Whipple (Am. Jour. Physiol., 1916, xl, 332) for measuring bili- rubin in the plasma may be used here. Tests for urobilinogen and urobilin are applied directly to the plasma. Ehrlich's and Schlesinger's reagents are both employed. One or two volumes of saturated alcoholic solution of zinc acetate precipitates most of the protein which is then removed by filtration. Five to ten drops of 4 per cent dimethylamidobenzaldehyde in 50 per cent HC1 is added. The fluorescence and a pink to dark red color develop, which give the characteristic spectral lines in the presence of urobilinogen and urobilin. Dialysis.-The jaundiced plasma is dialyzed through collodian sacks into small amounts (5 to 10 c.c.) of water and the dialysate tested by inspection and nitric acid to determine the presence and the approximate amount of water dialyzable pigment. The latter amounts to considerable in obstructive jaundice and to practically nothing in hemolytic jaundice. In the presence of water dialyzable pigment the plasma is dialyzed for twenty-four hours in running water and the amount of nondialyzable pigment remaining is esti- mated as above described. In the absence of water dialyzable pig- ment, dialysis is carried out into small amounts of 50 per cent alcohol solution and the tests made. Heat coagulation of the protein and filtration give a yellow pre- cipitate and leave a colorless filtrate in the presence of water non- dialyzable pigment, while the filtrate is yellow in the presence of water dialyzable pigment. After salting out completely or frac- tionally to completion, the proteins then precipitated show the 140 METHODS IN MEDICINE yellow color, when the filtrate is clear in the case of water non- dialyzable pigment and yellow in the presence of water dialyzable pigment. Pigment attached to the protein may be extracted with alcohol but is insoluble in ether, petroleum ether, dilute acids, and alkalis. Diazo Reaction.-Van den Bergh has applied Ehrlich's diazo reagent as a chemical test for the detection and differentiation of minute amounts of either the free or the protein-fixed bilirubin in the blood plasma. The Ehrlich's diazo reagent is freshly made up of 25 c.c. of solution I (sulphanilie acid 1 gram, concentrated hy- drochloric acid 15 c.c. and distilled water 1000 c.c.) and % c.c. of solution II (sodium nitrite 0.5 gm. and distilled water 100 c.c.). One c.c. of this mixture is added to 1 c.c. of blood plasma. The instant appearance of a bluish-violet color, which is maximal in ten to thirty seconds, is considered a direct or immediate reaction. The occurrence of a direct reaction indicates free bilirubin in the blood plasma and consequently signifies obstructive jaundice. A delayed reaction (one in which a reddish color which gradually deepens appears in from one to fifteen minutes) indicates impaired liver function An indirect reaction is one in which the direct test gives no color change, while, after 1 c.c. of blood plasma is mixed with 2 c.c. of 96 per cent alcohol and the precipitate thrown down, and 1 c.c. of the clear supernatant fluid treated with % c.c. of the reagent, gives an immediate violet red color. The indirect reaction is due to the liberation by the alcohol of protein bound bilirubin. This signi- fies a hemolytic or functional jaundice. Sabatini proposed a modification of the above which is more del- icate. He added to 6 c.c. of a 12 per cent solution of hydrochloric acid in distilled water 0.1 c.c. of a solution of sodium nitrite. After thorough mixing 0.3 c.c. to 0.5 c.c. of this mixture is added to 1.5 c.c. of the blood plasma. The color response is a brilliant green, the intensity of which is proportional to the bilirubin con- tent. The color slowly fades out. Bile Salts.-The simultaneous study of the bile salts in the blood plasma and in the urine is necessary in the differentiation of "Dis- sociated Jaundice." Blankenhorn obtained bile salts relatively free of lecithin and cho- lesterin by dialyzing 5 c.c. of plasma into 5 to 15 c.c. of water or SPECIAL PROCEDURES FOR GASTROINTESTINAL CASES 141 50 per cent alcohol. The dialysate from two or four of such dialyzers, after dialysis has gone for twelve hours, is collected and concentrated. Pettenkofer's test is applied by placing 2 c.c. of concentrated dialysate in a small flask with 2 or 3 drops of a 1 to 1000 aqueous solution of furfurol. The contents of the flask are kept at 60° C. by immersion in a water-bath. The mixture is agitated and 2 c.c. of concentrated sulphuric acid is added drop by drop. A pink or cherry red color turning to purple is a positive reaction. In sufficient concentration bile salts allow posi- tive identification by the spectral absorption bands. While the Pettenkofer test shows a cherry red color, the spectrum shows a wide absorption band in the blue (beyond F), but when the cherry red turns to purple the band in the blue fades and a smaller band develops in the orange (near D, between D and C). In high concentrations of bile salts both absorption bands are visible at once and the definition is good. In low concentrations, however, the band in the blue usually fades before the band in the orange appears, and the definition of the lines is distinctly less. Ignatowsky recommends the use of Czapek's capillary manom- eter to detect and roughly quantitate bile salts in the blood plasma and urine. Measurable surface tension changes are produced by the presence of as little as 0.02 per cent of bile salts in the fluid. References: Hoover, C. F. and Blankenhorn, M. A.: Arch. Int. Med., 1916, xviii, 289. Blankenhorn, M. A.: Arch. Int. Med., 1917, xix and 1921, xxvii, 131. Van den Bergh, A. A. H.: Presse Medicale, 1921, xxix, 441. Sabatini, G.: Policlinico, Rome, 1922, xxix, 837. Ignatowsky, A. I.: Wiener klin. Wochenschrift, 1922, xxxv, 958. The Fibrinolysin Test The antemortem occurrence of pathologic fibrinolysis forms the basis of the test. Since the clot from any specimen of blood will in all probability undergo a certain amount of dissolution if left in its own serum a sufficient length of time, it becomes necessary to define clearly the limitation of pathologic fibrinolysis. It may be safely stated that any blood, the clot of which dissolves completely in twelve hours at body temperature, is pathologic. Method.-Collect 10 to 15 c.c. blood in a sterile tube and place in the incubator at 37° C. and examine after twelve hours and again 142 METHODS IN MEDICINE at the end of twenty-four hours. The serum may be used for the Wassermann test. Reference: Goodpasture, E. W.: Fibrinolysis in Chronic Hepatic Insufficiency. Johns Hopkins Hosp. Bull., November, 1919, xxv, 330. INTESTINAL FUNCTION TEST Intestinal function tests are not numerous and as a rule not so spectacular as the tests of gastric and duodenal function. The careful study of the stools, with the patient on a known food in- take, will yield satisfactory results. The Schmidt-Strasburger diet consisting of a well-balanced diet of about 2,185 calories gives the digestive tract a definite amount of work and at the same time furnishes a residue, the parts of which can be easily recognized. Schmidt-Strasburger Diet DIET NO. 2 6:30 A. M. Milk 375 c.c. Zwieback (2 slices) 66 gm. 9:30 A. M. Bouillon, 375 c.c. % egg. 11 A. M. Milk 375 c.c. 1 egg. 12 noon. Oatmeal gruel, prepared from Oatmeal 40 gm. Milk 166 c.c. Sugar 10 gm. Egg % 500 c.c. Hamburger steak (well done) prepared from .... Raw beef 100 gm. Butter 12 gm. 100 gm. Mashed potatoes prepared from Potatoes 190 gm. Milk 60 c.c. Butter 8 gm. 250 c.c. 3:30 P. M. Milk, 375 c.c. Egg, 1- Zwieback, 1 slice (33 gm.) 6:30 p. M. Oatmeal gruel, 500 c.c. (prepared as above). Total make-up: Milk 1.5 Liters Zwieback 100 Grams. Butter 20 " Sugar 20 " Steak (raw wt.) 125 " Potatoes (raw wt.) 190 " Protein 126.25 gm. Fat 83.4 gm. Carbo. 218.5 gm. Calories 2183.8 DIET No. 1. Same as above except for absence of meat and potato. SPECIAL PROCEDURES FOR GASTROINTESTINAL CASES 143 After two or three days on this diet, the stool examinations may be begun. The length of time a given meal is in the gastrointestinal tract may be estimated by the use of a 3-gram capsule of finely powdered carmine or charcoal taken with the first part of the meal. The time between the taking of the carmine by mouth and its ap- pearance in the stool measures the length of digestive process. The pigment marks the beginning of the stools of the test diet. The stools show the results of gastric, duodenal, pancreatic and hepatic function together with whatever changes intestinal diges- tion has brought about. It is impossible to separate the intestinal digestive effects. The twenty-four hour amount of stool on the test diet should be between 100 and 250 grams. It should be formed and moderately soft and light yellow to dark brown in color and with an odor of skatol and somewhat of indol. Bulky bowel movements may be due to faulty digestion of mainly gastric or pancreatic origin, or to faulty absorption in the intestine as the result of overactive peristalsis or alterations of the absorp- tive tissues. Large amounts of undigested starch, meat, fats, and soap call for estimations of the output of carbohydrate, protein and fat compared with the intake and with the normal output percentages. In the case of large outputs of fat, the ratio of the amounts of neutral fat to fatty acids and soaps is to be estimated. The amounts of mucus and pus can only be estimated very roughly. The amount of albumin in the feces may be estimated by extrac- tion of a definite amount of stool with a definite amount of water for several hours, and quantitating the amount of albumin in the filtrate by the Esbach albuminometer method. The presence of bile can be detected by the saturated solution of bichloride of mercury test and the urobilin and urobilinogen quantitatively estimated by the Wilbur and Addis method described below. The microscopic examination of the stool verifies the macroscopic and chemical observations. The quantity of undigested starch, the quantity and condition of meat fibers as to striations and nuclei, and the quantity and proportion of undigested fats, fatty acids, and soaps add some quantitative value to the microscopic examination. 144 METHODS IN MEDICINE Further details as to the examination of stools microscopically and for blood will be given below. References: Strasburger, J.: Deutsch. Arch. f. klin. Med., 1868, Ixi, 584. Schmidt, Ad., and Strasburger, J.: Die Faeces des Menschen mit klinischen Untersuchungsmethoden, Berlin, 1903. Tests for Fat Indigestion Fatty or greasy, butter-like or oily stools are seen in some cases of pancreatic insufficiency and jaundice, and when found, they are of considerable interest and diagnostic significance. The fat indi- gestion may be the result of insufficient chemical splitting, in- sufficient saponification, or insufficient absorption, or all three together. The macroscopic examination along with the reaction of the stool is only suggestive. The microscopic examination of the stools for fats with the aid of stains is considerably more enlightening. Fresh filtered alco- holic Sudan III mixed with a drop of emulsified stool shows neutral fat as orange red to blood red droplets, the fatty acids as orange red short delicate curved needle-like crystals in masses, and the soaps as unstained long needle-like or short plump crystals in fan- like clusters. Dilute carbol-fuchsin (5%) does not stain neutral fat, but colors fatty acids a brilliant red and soaps a dull red. If there is a question of a preponderance of soaps, a drop of glacial acetic acid may be added, the preparation heated and stained again with Sudan III, which will demonstrate an increase in fats if soaps were orig- inally present. These tests give an idea of the relative amounts of the fatty substances. The exact proportions of fats, fatty acids, and soaps in the feces can be estimated. The total fats, neutral fat plus fatty acids plus soaps; the neutral fats plus fatty acids and the soaps separately; the neutral fats and fatty acids separately; and the soaps alone, can be determined. The Liebermann-Szekely method for total fatty substances con- sists in saponification of all the fats in the 24-hour stool amount, by boiling a weighed portion of the feces with 3'0 per cent potassium hydroxide, then splitting off the fatty acids with dilute sulphuric acid, dissolving the fatty acids in benzine, petrol, or petroleum ether and alcohol, and titrating with standard alcoholic potassium SPECIAL PROCEDURES FOR GASTROINTESTINAL CASES 145 hydroxide to neutrality with phenolphthalein indicator. The total amount in the 24-hour specimens is calculated from these data. Midler's method is used for separating and estimating neutral fat and fatty acids from soaps. A weighed portion of the 24-hour feces output is dried at 100° C. and mixed with several times its quantity of previously prepared sand. The prepared sand consists of sand that for several days has been subjected to a cleaning process with water, alcohol, hydrochloric acid, and finally dis- tilled water. The mixture of dried feces and sand is placed in a Soxhlet apparatus and extracted with ether until no more fat can be removed, which is usually within ten hours. The ether used for the extraction is allowed to evaporate and the residue is washed thoroughly with luke-warm water, dried again and weighed, thus giving the actual amount of neutral fat plus fatty acids contained in the sample. From this the amount of these two substances in the 24-hour feces output can be easily estimated. The ether ex- tracted feces are kept for soap determinations. Volhard's method may be used for estimating separately the neutral fats and the fatty acids. A weighed amount of the residue of the ether extraction is dissolved in alcohol-ether and titrated with standard alcoholic potassium hydroxide with phenolphthalein as the indicator. The amount of fatty acids is thus estimated, and the difference between the total amount of the ethereal residue and the amount of fatty acid as determined by titration is the amount of neutral fat. The amount of soaps may be calculated from the figures of the total fatty substances and the neutral fatty acid amounts. The soaps, however, may be directly determined on the ether extracted feces taken from the Soxhlet apparatus (above) and boiled with hydrochloric acid alcohol, then dried again and re- extracted with ether in a Soxhlet apparatus. The fatty acids are split off from the soaps by the acid and after adding alcohol the amount of fatty acid obtained from the soaps can be estimated by titration. The results are transformed by calculation into the equiv- alent amount of soaps. Muller's simpler method for unsplit and split fats, that is neutral fats and fatty acids plus soaps, consists in boiling the dried feces specimen directly with hydrochloric acid alcohol, thus splitting off all the fatty acids from the soaps, ancl leaving only neutral fats 146 METHODS IN MEDICINE and fatty acids to be estimated from the ethereal extract, as above described. References: Liebermann, Leo, and Szekely, S.: Pfliiger's Arch. f. Physiol., 1898, Ixxii, 360. Miiller, Friedrich: Ztschr. f. klin. Med., 1887, xii, 45. Volhard, Franz: Ztschr. f. klin. Med., 1901, xliii, 397. Tests for Occult Blood in the Stools The guaiac test is usually considered more reliable than the benzidin tests, which are as a rule too sensitive. With most tests for occult blood it is advisable for the patient to be on a hemo- globin-free diet for four days before the test, if reliable results are expected. Faint reactions are often due to substances other than blood, while strong reactions indicate blood. The benzidine test, as modified by W. T. Vaughan, is a clean, simple and reliable test. The reagent consists of an amount of benzidine crystals about the size of a match-head. The benzidine crystals are placed in a small, clean test tube, about 1 c.c. of glacial acetic acid and % c.c. of 3 per cent hydrogen peroxide are added and the whole mixed. One or two drops are placed on each smear of feces and the latter then examined against a light background for the green color of a positive reaction. Reference: Vaughan, W. T.: Jour. Lab. and Clin. Med., Mar., 1917, ii, 437. The benzidin test with J. Wohlgemuth's reagent is fairly reliable. The two necessary solutions, A and B, are kept in separate dark bottles. (A) Benzidin crystals (C.P.) 0.5 gm. Acetic Acid 50% 50.0 c.c. Dissolve without heating. (B) Dextrose 5.0 gm. Warm the alcohol to dissolve Ortizon 2.0 gm. the dextrose, add the ortizon, Alcohol 50% 50.0 c.c. allow to stand for 15 min. and filter off the sediment. The solutions when kept separate in dark bottles are reliable for six months. When fresh the mixture of the two is efficient for sev- eral hours, while if the solutions are several months old, the mixture is active for about half an hour only. To make the test, mix accurately equal parts of solutions A and SPECIAL PROCEDURES FOR GASTROINTESTINAL CASES 147 B. Drop the mixed solutions on thin smears of feces always retain- ing at least one smear as a control. If there is variation of intensity of reaction on smears from various parts of the feces, it indicates possible blood from hemor- rhoids, as blood from the upper gastrointestinal tract is homogene- ously mixed with the stool as a rule and presents the same intensity of reaction in all smears. Spectroscopic Test for Occult Blood in Stools Acid hematin gives distinct spectral bands, but in the stools hematin is practically all reduced. Hemochromogen, in the form of the pyridin derivative may, however, be looked for spectro- scopically. In some cases most of the occult blood may be present in a still more reduced form as hematoporphyrin, which also gives spectral bands. Method.-Mix 5-15 gm. of the stool with acetone and extract. Filter off the acetone extract. Coloring matter may be removed with water. The acetone and water extracted residue is placed in a mortar and mixed with Glacial Acetic acid 1 part Ethyl acetate or ether 3 parts. Filter and add to the filtrate % volume of pyridin (C5H5N) and a drop of fresh ammonium sulphide (NH4)2S or preferably hydra- zine hydrate (H,N - NHOH). If only a trace of blood is present there is a band at 560 in the spectroscope. If blood is present in large amounts there is a weaker band at 523' to 526. These are the hemochromogen bands. Chlorophyl in large amounts masks the hemochromogen band. Occasionally, the acetic acid ethyl acetate extract, if examined before the addition of pyridin and ammonium sulphide, shows an intensification of the band at 550, due to the superposition of the hemochromogen line. After the addition of % volume of pyridin and before the addition of a drop of fresh ammonium sulphide add 1 or 2 c.c. of distilled water and shake lightly, then add 1 or 2 c.c. of ether to facilitate layer formation. The chlorophyl band at 650 still remains visible in the aqueous layer but most of the chlorophyl is in the ether layer while the blood pigment is below. 148 METHODS IN MEDICINE Now add one or two drops of the fresh ammonium sulphide solu- tion, which falls through the ether layer into the aqueous layer and if blood is present the band appears at 560. Layers of one centimeter or more in thickness should be used. Hematoporphyrin may be the form in which most of the occult blood may be present. To test for this after the addition of a little ether extract dilute the acetone extracted residue with 5 per cent hydrochloric acid sufficient in amount to give 1 or 2 c.c. for examination after filtration. In rare instances the color may be too dark and the procedure is repeated with 2.5 per cent HC1. The hematoporphyrin band lies at 570. Spectral Bands strong 645 - 635 weak 576 - 550 C - 656 A - 628 D - 588 E - 528 (1) Acid Hematin strong 560 - 554 weak 593 - 575 D 588 E 528 (2) Pyridin Hemochromogen (3) Acid Hematoporphyrin weak 605 - 600 strong 570 - 555 a - 628 D 588 (4) Chloroph;! strong 675 - 650 weak 620 - 605 weak 570 - 560 strong 545 - 525 B 685 E 656 Concentration of Ova in Stools To about 2.5 c.c. to 5.0 c.c. of a medium thick stool emulsion in a centrifuge tube add % to % its volume of concentrated hydro- chloric acid solution. Mix thoroughly. Add 2 to 4 c.c. of ether. Shake thoroughly. The debris ab- sorbs the ether, becomes light, and along with the fat rises to the top of the mixture and can be removed. The mixture can then be centrifuged and the ova, with a small amount of debris, are usually at the bottom. In rare cases, how- ever, due to the lighter specific gravity of the ova, or for unknown reasons, the method fails. In such cases the method of precipitating the debris and floating the cells may be tried. SPECIAL PROCEDURES FOR GASTROINTESTINAL CASES 149 A medium thick stool and water emulsion is placed in a centri- fuge tube. After centrifuging, the water is poured off and 42.5 per cent calcium chloride solution is added. The tube is centri- fuged and the debris is precipitated, while the eggs rise to the top almost free of debris. Concentration of Entamoeba Cysts in Stools One to five grams of feces are emulsified by shaking with normal saline solution for at least thirty minutes. The emulsion is poured into a separatory funnel, mixed with %0 to % volume of ether and shaken for 30 seconds. Allow to stand for 5 to 15 minutes. Then withdraw the saline and centrifuge at low speed for 2 to 3 minutes. The cysts are at the bottom with a relatively small amount of debris. The cysts after this procedure are fifteen times as numerous as when the direct examination of the stool is made. If it seems desirable to have still greater concentration, the procedure may be extended from this point. The supernatant liquid is poured off after decantation. The tube is filled with nor- mal saline and again thoroughly shaken. Centrifuge for 10 seconds and discard the material thrown down. Centrifugalize the re- mainder for half the regular time for 15 c.c. tubes, which is 1% minutes at 1200 R.P.M. or 2% minutes at 600 R.P.M. This brings down all the cysts. For the concentration of the cysts of Lamblia intestinalis even greater care must be taken and more thorough centrifugalization done. UROBILINOGEN AND UROBILIN METHODS Duodenal Contents, or Bile A measured amount of bile is mixed to a paste in a mortar with fullers' earth and left for some hours. An equal amount of the alcoholic solution of zinc acetate is then added and the mixture filtered under pressure, and the remainder washed with measured amounts of zinc acetate alcohol. In this way almost all of the bilirubin is absorbed, and though no doubt there is some loss of urobilinogen and urobilin, the comparatively small amounts found in the washings compared with the quantities present in the first 150 METHODS IN MEDICINE filtrate seem to indicate that the fullers' earth has very much less capacity for absorbing urobilin than bilirubin. Small amounts of urobilin or urobilinogen could no doubt be overlooked by this method. The Ehrlich solution is added in the same proportion as in the urine (see below) but the dilutions must be made with alco- hol instead of water. Stools All the feces passed in the twenty-four hours are collected in the same receiver, the stools being protected from light. They are then washed into a large graduate and thoroughly ground up with water into a homogeneous paste, and water added to 0.5, 1, or if necessary 2 liters, depending on the quantity of stool. After thorough mixing, 25 c.c. are taken and 75 c.c. of acid alcohol (95 per cent alcohol, 1,600 c.c.; concentrated hydrochloric acid, 25 c.c., and water 800 c.c.) are added. The mixture is then put into a shaker for about half an hour A considerable number of ex- tractives were tried by Wilbur and Addis for removing the urobilin from the stools, but none were found so efficient as alcohol with hydrochloric acid. After thorough mixing in the shaker, an equal quantity of a saturated solution of zinc acetate in alcohol is added and the mixture is filtered. After adding 2 c.c. of Ehrlich's reagent to 20 c.c. of the filtrate, the solution is put aside in a dark place until the next day. The addition of zinc acetate is not absolutely essential, but in some cases Wilbur and Addis observed an inten- sification of the urobilin band following its use, and it is perhaps an advantage to make the urine and stool readings as far as pos- sible under the same conditions. The development of the uro- bilinogen band is not always complete until six hours have elapsed, but thereafter there is no loss of urobilinogen or urobilin for a long time, although this is not the case with the zinc acetate fil- trates before the addition of Ehrlich's solution. The reading is made in the same way as with the urine (see below) and the total amount calculated for the volume of stool after grinding up with water, the dilution of the 25 c.c. by acid alcohol and zinc acetate being taken into account. Instead of using tap-water for dilution of the final extract, 60 per cent alcohol is required to avoid the de- velopment of a precipitate. SPECIAL PROCEDURES FOR GASTROINTESTINAL CASES 151 Urine The method of collection of the twenty-four-hour urine has a considerable effect on the total spectroscopic reading. The vessel in which the urine is collected should be of dark brown glass and should be kept in darkness. Thymol crystals should be added, for even in cases in which no obvious fermentation had occurred Wilbur and Addis sometimes found a diminution in the total amount if no preservative was present. After measuring the amount of the twenty-four-hour urine, 10 c.c. are mixed with 10 c.c. of a saturated alcoholic solution of zinc acetate, and after a few minutes filtered. If a number of urines are being examined at the same time it is convenient to have test-tubes graduated at 10 and 20 c.c. Ten c.c. of the filtrate are taken and 1 c.c. of Ehrlich's solution (Paradi- methylamidobenzaldehyd, 20 gm.; concentrated hydrochloric acid, 150 c.c.; water, 150 c.c.) is added. Wilbur and Addis found that this amount produced a sufficient concentration of acid in the mix- ture to give the maximum intensity of the urobilin band and con- tained enough of the paradimethylamidobenzaldehyd for the reac- tion with urobilinogen. The development of the urobilinogen band is not instantaneous but it was found that as a rule it attains its full intensity in a quarter of an hour. The action can be greatly accelerated by heating, but this is to be avoided. It is better to wait for an hour before making the reading, and during this time the solution should be kept in the dark. After three or four hours there is a diminution of the urobilin and uro- bilinogen in filtrates from urines, so the estimation should be made not later than three hours after adding the Ehrlich solution. Cit- ron's or Reichert's hand spectroscopes are the most convenient instruments to use. The filtrate is washed into a graduate and diluted with tap-water until first one and then the other bands of light absorption have disappeared when the full amount of light enters the spectroscope, but are still visible when the light is partly shut off. This gives a fairly definite end-point, and there is no great variation in the readings made by different persons. It is important, of course, that the light shall be always of ap- proximately equal intensity. The readings are made in a dark room with a Tungsten electric bulb, holding the spectroscope close to the source of light. In highly colored urines one may be in 152 METHODS IN MEDICINE doubt as to whether or not a trace of urobilin is present, for there may be so much general absorption of light as to obscure the urobilin band in the undiluted filtrate. There is no such difficulty with the urobilinogen band which lies between the red and yellow where there is no marked light absorption. With urines containing bile, if the amount of urobilin is not very large, it is necessary to add some fullers' earth and to leave the mixture standing for some time before filtration. If this is done the urobilin band can usually be read even in the undiluted filtrate. The dilution re- quired gives the value for 5 c.c. of urine. If this figure is mul- tiplied by the number of 5 c.c. quantities in the twenty-four-hour urine, the number of dilutions which would have been necessary if all the urobilinogen and urobilin in the twenty-four-hour amount had been concentrated in a volume of 5 c.c. is obtained. For in- stance, if in a twenty-four-hour urine measuring 1,000 c.c. a read- ing of ten dilutions for urobilinogen and of twenty for urobilin were made, the total urobilin would be 30 x 200 = 6,000. Wilbur and Addis tried to determine the dilution value of definite weights of urobilin prepared from bilirubin, but different preparations varied so much in their dilution value that it was obvious to them that they were not dealing with pure urobilin and they abandoned any attempt to express their results in milligrams of urobilin. Reference: Wilbur, R. S., and Addis, T.: Arch. Int. Med., 1914, xiii, 235. TECHNIC FOR FINDING MERCURY IN STOMACH CONTENTS, FECES AND URINE Method, of Vogel and Lee.- 1. Take as many c.c. of stomach contents or emulsified feces as are obtainable up to 150 c.c. or 150 c.c. of urine. 2. Acidulate with 5 c.c. concentrated HC1. 3'. Evaporate over free flame to 25-30 c.c. 4. Add 2 c.c. HC1 to replace any loss. 5. Add enough, about 2 grams, potassium chlorate to oxidize thoroughly the organic material present. When this is affected, the fluid becomes pale or colorless. 6. Dilute to about 60 c.c. with distilled water. 7. Boil vigorously until chlorine gas previously evolved has been SPECIAL PROCEDURES FOR GASTROINTESTINAL CASES 153 driven off, which is shown by the absence of the chlorine odor from the steam. (The solution usually darkens on cooling.) 8. A piece of copper wire, (about 18 gauge) 4 cm. long, bent back on itself twice and cleansed by boiling for a short time in a test tube with dilute HC1, is dropped into the solution and al- lowed to remain for an hour or more. If considerable amounts of mercury are present, the wire will 1)0 found to be coated with a silvery film of metallic mercury, but this is not sufficient to establish the identity of the metal, and if it exists only in traces the changes in the appearance of the wire may be inconclusive. The wire is accordingly removed from the dish with a glass rod, is washed with a little water, and is gently dried by rolling it on a piece of filter paper, pains being taken to avoid unnecessary handling and attrition. It is then allowed to slip to the bottom of a glass test tube (3-5 mm. in diameter and 15 cm. long) and is followed by a cylindrical plug of goldleaf (obtainable from any dentist) which is pushed into the tube until it is within 2 cm. of the wire. 9. Hold the tube horizontally and heat the portion around the copper wire by gentle introduction into a small flame. Examine the goldleaf frequently to see whether mercury is being deposited. If there is only a small trace of mercury, it may only cause a slight pale discoloration of the gold. It is seen to the best advantage with a hand lens or by removing the pellet and examining with the low power under the microscope. If the deposit is large, it is easy to see. If the gold is too close to the wire, the heat may cause a deposit of mercury which at first was distinctly visible to be- come diffused, so that it grows less evident. In doubtful cases repeat the process. If further confirmation is wanted, the goldfoil may be suspended in a tube containing a few crystals of iodin which are then very gently warmed. The mercury becomes con- verted into red mercuric iodide. If the amount is large, the metal may be distilled by heating the goldfoil in the tube and looking with the lens for a deposit of very fine minute droplets of metallic mercury in the cooler parts of the tube. Some concrete idea of the actual amount of mercury present may be gained by weighing the goldfoil. Note: Corrosive sublimate is readily reduced by organic matter to metallic mercury and the latter, as well as mercuric chloride, 154 METHODS IN MEDICINE is volatile to a slight extent with steam, so that this must be borne in mind in evaporating or digesting solutions which may contain very minute amounts of the poison. The quantity of mercury which the coppei' is capable of abstracting from the fluid is a func- tion not only of the concentration of the solution, but also of the contact, so that if the test is negative after the wire has been im- mersed for 1 to 2 hours, another piece of wire should be dropped into the fluid and allowed to remain for a longer time, even over- night. This test will show readily even with the unaided eye mercury in such a dilute solution as 1:100,000 in clinical conditions, and will show up to 1:1,000,000. On examination of urine of twelve patients who were given two grains of calomel the preceding night, the test was positive in ten cases. Reference: Vogel, K. M., and Lee, O. L.: Jour. Am. Med. Assn., 1914, Ixxii, 532. Method of Willard and Elliott for Mercury Detection 1. Five hundred c.c. of the fluid to be tested are acidulated with from 10-20 c.c. of concentrated HC1. Place in a large bottle. 2. Add 1 or 2 gm. of copper dust. (Obtainable from a chemical house or any bronze paint manufacturer.) 3. Cork bottle, shake thoroughly for several minutes and allow to stand until the copper has settled. (If possible overnight.) 4. Decant off the larger portion of the overlying fluid. The remainder is thoroughly shaken and filtered, care being taken that all of the copper is washed out of the bottle. 5. The residue is washed first with alcohol then with ether. 6. Then the filter is spread out and air dried. 7. After the copper dust is thoroughly dried, place it in a small bulb made from 4 to 6 mm. glass tubing. A small funnel made by drawing out a test tube is used in placing the copper in the bulb. 8. To the copper dust add 1 or 2 small pieces of magnesite which on being heated gives off carbon dioxide gas, and forces the mer- cury along the tube. A small piece of washed asbestos is inserted into the tube just above the bulb to prevent the copper dust from contact with the goldfoil (that is to be inserted) while the bulb is being heated. SPECIAL PROCEDURES FOR GASTROINTESTINAL CASES 155 9. Constrict the tube above the bulb 1 inch from the end (just above the asbestos). Insert a small piece of dental goldleaf into the constricted portion. Keep the goldfoil perfectly cool by wet filter paper. 10. Heat the bulb gently and uniformly to avoid a blow out. Gradually bring to a red heat at which time all traces of mercury are deposited in the goldleaf as amalgam %2i000 mg- °f mercury is visible to the naked eye. In higher dilution a hand lens is nec- essary. 11. With blood and fluids with protein contents high, distil with equal amounts of concentrated sulphuric acid. Use the distillate. Reference: Elliott, J. A.: Jour. Am. Med. Assn., 1917, Ixviii, 1693. DETECTION OF METHYL ALCOHOL Robinson's Test Principle.-The methyl alcohol is converted into formaldehyde by potassium permanganate. The solution is then added to acidu- lated milk and the mixture gently heated until a pink color de- velops. This test is sensitive to 0.01 per cent of methyl alcohol. Qualitative Test.- 1. Alkalinize 100 c.c. of the stomach contents or material sus- pected of containing methyl alcohol with sodium carbonate. 2. Dilute the alkalinized solution with an equal volume of dis- tilled water. 3. Distil the solution completely and divide it into two equal volumes of 100 c.c. each, one for qualitative and one for quanti- tative tests. 4. Redistil 100 c.c. of the distillate. 5. To the first 10 c.c. coming over add 3 c.c. of a 1 per cent solu- tion of potassium permanganate. 6. Heat this solution to 43.3° C. (110° F.) and agitate the vessel constantly until the odor of ethyl aldehyde is perceptible. 7. If the solution decolorizes, add more permanganate solution, 1 c.c. at a time, until the pink color is restored. 8. Add a few drops of commercial hydrochloric acid to precipi- tate the excess of permanganate as brown manganese hydroxide and filter. 156 METHODS IN MEDICINE 9. Pour the colorless filtrate into a porcelain casserole and add 10 c.c. each of water, fresh milk, and hydrochloric acid. 10. Heat the mixture to boiling, agitating constantly until a bright permanent pink develops, which will occur if as much as 0.01 per cent or more of wood alcohol is present in the suspected liquid. Quantitative Estimation.- A rough estimate of the relative amounts of ethyl and methyl alcohol present in a suspected liquid may be obtained. The sus- pected liquid is poured directly into the hygrometer and Zeiss refractometer and the readings of the specific gravity and per- centages are compared with the reference table and empiric for- mula. (Compare with Leach: Food Inspection and Analysis; 4th edition, page 782.) Accurate results may be obtained by using the 100 c.c. of the distillate obtained in steps 1, 2, and 3, above. 11. The 100 c.c. of distillate for quantitative study is cooled to 16° C. (60° F.) and the specific gravity estimated. 12. The specific gravity is compared with tables to estimate the percentage of alcohol by weight and volume. 13'. The distillate is then poured into a Zeiss Immersion refrac- tometer and the scale reading is recorded and compared with the reference table to ascertain whether pure ethyl alcohol, pure methyl alcohol, or a mixture of the two is present. 14. If both are present, obtain the percentages of each by apply- ing the empiric formula. References: Robinson, W. C.: Department of Public Health, Philadelphia, Pa. Quoted by Ziegler, S. L.: Jour. Am. Med. Assn., Oct. 1, 1921, Ixxvii, 1160. CHAPTER XIV RENAL FUNCTION TESTS Phthalein Test Directions.-The patient's bladder should be completely emptied. Then inject intramuscularly, into the lumbar muscles, the gluteal muscles, or, in well-developed individuals, into the triceps muscle, exactly one (1) c.c. (6 mgm.) (preferably measured in a Tuberculin Syringe) of the phenolsulphonephthalein solution. The stock bottle of phthalein solution on the ward should be aseptically capped by a sterile rubber nipple. To secure the 1 c.c. for injection, the surface of the nipple is rubbed with an alcohol sponge and the rubber then pierced with a hypodermic needle and the bottle turned up and slightly over 1 c.c. withdrawn. The air is then forced out of the syringe over the solution and exactly 1 c.c. measured and injected. If the stock solution is contained in ampules of 1 c.c. + capacity, the ampule is opened in the ordinary way, the contents withdrawn, exactly 1 c.c. measured in the syringe and injected. Give the patient 200 c.c. water ten minutes after the time of injection and again in one hour. The time periods should be calculated from the time the urine, rendered alkaline, first shows coloration. For convenience, allow ten minutes (10 min.) for this, which is the time required for the absorption of the dye. Then at the end of an hour and ten min- utes from the time of injection, that is, one hour after absorption, the entire contents of the bladder should be carefully collected and the amount of dye excreted accurately estimated in a colorimeter. Again at the end of the second hour (2 hours) from the time of absorption that was ten minutes after the injection, another such collection and examination is made. (If necessary, catheterize the patient, using strict aseptic tech- nic.) 157 158 METHODS IN MEDICINE The percentage estimation should be carried out as soon as the urine is voided. If there is necessary delay, keep the specimen acid. To estimate the quantity excreted, use the Hellige's colorimeter as routine, or the Dunning colorimeter. When no other is at hand use two 50 c.c. graduates, one containing 50 c.c. of the unknown the other 5 or 10 c.c. of a 100 per cent standard which can be diluted to match the unknown and the percentage estimated from the amount of dilution required. The Duboscq colorimeter is used if the most accurate results are desired. Dilute the specimen to about 200 c.c. with water and render alka- line by the addition of 10 c.c. of a 5 per cent sol. of NaOH, or 1.5 to 2 c.c. of a 40 per cent sol. of NaOH. If the coloration of the alkaline specimen at this point is slight, showing a small excretion of the "phthalein" then the dilution should be carried only to 250 c.c. or 500 c.c. and the reading against the standard divided by 4, or 2, as the case may be. In ordinary cases the specimen is diluted with sufficient water to make it measure 1000 c.c. Enough of the solution should be clarified by filtration to fill the trough of the Hellige, the open ampule of the Dunning, or the cylinder of the Duboscq and the comparison with the "standard" carried out. The "standard" for the Hellige and Duboscq is to be made up by the assistant resident in chemistry, who is responsible for the proper standardization of all quantitative apparatus in use in the medical laboratories. One c.c. made up to 10 c.c. with water will serve as the stock standard and is permanent as long as it is not alkalinized. The 1 c.c. of this solution made up to 100 c.c. with water and alkalinized serves as the standard, really equaling 1 c.c. (.006 gm.) in 1000 c.c. This standard fades when exposed to the light for a day or so and should consequently be made up fresh and the Hellige wedge filled each day estimations are made. If great care is exercised and the standard is kept in the dark when not in use, a bi-weekly or even a weekly standardization will suffice. The Dunning Colorimeter has a sealed set of standard percent- ages, but these also fade and should be kept in the dark. RENAL FUNCTION TESTS 159 Methods of Administration of Phenolsulphonephthalein The intramuscular injection method is the routine method. The dye appears in from 3.5 to 7 minutes, averaging 5 minutes, and 60 per cent to 70 per cent is excreted in the first hour and a total of 65 per cent to 85 per cent in two hours. In edematous, cardiac and nephritic cases and in genito-urinary work with the aid of the cystoscope and ureteral catheterization, the intravenous method is preferable. The dye appears in 2 min- utes and is excreted at the rate of 1 to 1.5 per cent per minute totaling 65 to 80 per cent in the first hour. By having the ureteral catheters in separate tubes, the function of each kidney may be estimated individually. References: Rowntree, L. G., and Geraghty, J. T.: Jour. Pharmacol, and Exper. Therap., 1910, i, 579; ibid., 1911, ii, 393. Arch. Int. Med., March, 1912, ix, 284. Elliott, A. R.: Jour. Am. Med. Assn., June 5, 1915, Ixiv, 1885. Twelve-Hour Urinary Output Records Day and night volumes of urine must be carefully collected if it is hoped to use the comparisons in diagnosis. The fluid intake must be likewise accurately recorded. In some cases it is of ad- vantage to have a standard intake 1500 to 3000 c.c. depending on the patient's desires and the season. The collection of the specimens must follow a very definite sched- ule. The patient is asked to empty his bladder at exactly 6:3'0 a.m. The urine voided at this time is used as an admission specimen or not saved if the admission specimen has already been secured. All the urine passed from 6:30 a.m. throughout the day is saved and at exactly 6:30 p.m. the patient is again asked to empty his bladder, this voiding is added to the specimen that had accumulated since 6:30 a.m. and the day volume is thus completed, and prepara- tion made for the night volume. The night volume consists of all the urine passed from 6 :30 p.m. up to and including that passed at 6:30 a.m. of the following day. "When phthalein tests are done, the amounts in cubic centimeters of urine excreted at the ends of the first hour and second hour are recorded by the nurses in their output records and on the 12 hour specimen card which is attached to the patient's bottle. Thus 160 METHODS IN MEDICINE the 12 hour volume remains accurate. The added water intake for the test is, of course, added to the fluid intake record. The cooperation of the patient must be sought. It must be explained to him just what is wanted, how every voiding of urine must be saved and how each 12 hour specimen must be completed at exactly 6:30 o'clock in the morning and evening. The nurses and orderlies must likewise be carefully instructed if the desired results are to be obtained. Each twelve-hour specimen is kept from fermentation by toluol or chloroform and refrigeration. The specimens are then to be measured, the reaction and the specific gravity recorded, and the quantitative estimations of the chlorides and the albumin made. All these data together with the fluid intake figures are recorded on the white urine chart and are to be charted according to the standard cardiorenal chart scale and outline. (See Part V, Com- posite History.) The Two-hourly Renal Test Renal function may be estimated on the actual capacity of the kidney to excrete water and more particularly solids. The actual data are made up of the volumes, the specific gravities and the quantities of sodium chloride and nitrogen containing substances of the two-hour specimens of urine collected throughout the day, from 8 a.m. to 8 p.m., and of the complete night excretion, from 8 p.m, to 8 a.m., in a single specimen. Punctual collecting of spec- imens is absolutely essential. The diets most successful in these studies have been the (1) Mod- erately High Protein Diet of about 1,760 c.c. of fluid, 8.5 gm. of salt, and 13.4 gm. of nitrogen, and considerable quantities of purin substances in the soup, meat, tea and coffee, and the (2) Moder- ately Low Protein Diet with a protein equivalent of 3 to 4 gm. The use of a Normal Diet of three full meals taken at the regular hours of 8 a.m., 12 Noon, and 5 p.m. with a record of the amounts of food and fluid taken- at the meals and no food or fluid between meals, may be substituted but is not entirely satisfactory. The normal standards formerly advocated were as follows: A maximum specific gravity of 1.018 or higher, a variation of 9 de- grees or more between the minimum and maximum specific gravity readings, and a night urine of 400 c.c. or less with a specific gravity of 1.018 or over and a concentration of nitrogen of at least 1 per RENAL FUNCTION TESTS 161 cent. A fourth study of normals necessitated some revisions in these figures. It was found by Mosenthal that the maximum spe- cific gravity remained at 1.018 or over on the "high" diet, and 1.020 or more on the "low" and "normal" diets. The variations of 9 degrees or more in the specific gravities were found to hold good with cases in which the "high" or "low" diets were used but the variation was much less for the "normal" diet. It was also found that the specific gravity may be almost fixed but at a high level 1.020 or more, in normal individuals during hot weather. These smaller variations do not necessarily indicate that the kidney is abnormal if the specific gravity is 1.020 or more, but may point to a deficient available supply of water. The main error in the first standard was the low limit placed upon the night volume, i.e., 400 c.c. or less. The new standard places the night volume at 750 c.c. or less on high, low, or normal diets and the specific gravity of this specimen is of no special sig- nificance except that it is usually the maximum concentration of the test. The N and NaCl percentages in the night urine or the highest THE LOW PROTEIN DIET. BREAKFAST 8 A. M. Sherry 30 c.c. (May be omitted) Baked apples Stewed prunes Orange Hominy Cornstarch (% hominy) (]4 cornstarch) Butter Cereal Cream 15 c.c. Sugar DINNER 12 NOON. Sherry 30 c.c. (May be omitted) Potato (Baked or mashed) Stringbeans Cabbage Carrots Lettuce Onions Tomatoes Cucumber pickles Fruit cornstarch pudding Fruit tapioca pudding Sugar Butter SUPPER 5 P. M. SAME AS DINNER. 162 METHODS IN MEDICINE Containing 13.48 Nitrogen, 8.58 NaCl and 1,760 c.c. H2O. F or Date AU food must be salt free from the diet kitchen. Salt for each meal will be furnished in weighed amounts, 2.38 NaCl in a capsu'e accompanying each meal. Any salt unused is returned to the diet kitchen where it is weighed and the amount used is indicated on the chart. All food or fluid not taken must be weighed or measured after meals and charted in spaces beloio. Allow no food or fluid of any kind except at meals. Note any mishaps or irregularities that occur in giving the diet or collecting the specimens. NOTES Breakfast 8 A. M. THE HIGH PROTEIN DIET Boiled oatmeal-100 gm. Sugar-% teaspoonful Milk-30 c.c. 2 slices bread, (30 gm. each) Butter, 20 gm. Coffee, 160 c.c. Sugar, 1 teaspoonful Milk, 40 c.c. -200 c.c. Milk-200 c.c. Water-200 c.c. Vinner 12 Noon. Meat soup, 180 c.c. Beefsteak, 100 gm. Potato (baked, mashed, or boiled)- 130 gm. Green vegetables as desired 2 slices bread (30 gm. each) Butter 20 gm. Tea-180 c.c. Sugar-1 teaspoonful Milk, 20 c.c. -200 c.c. Water, 250 c.c. Pudding, (tapioca or rice), 110 gm. Supper, 5 P. M. 2 eggs, cooked in any style 2 slices bread (30 gm. each) Butter-20 gm. Tea-180 c.c. Sugar, 1 teaspoonful Milk-20 c.c. -200 c.c. Fruit, (stewed or fresh) 1 portion Water, 300 c.c. RENAL FUNCTION TESTS 163 percentages in any specimen are now considered normal if 1 per cent or higher, but not necessarily abnormal if less. The main results agree regardless of diet. The lowering of the maximum specific gravity and the increase of the night volume remain the most constant and reliable signs of impaired renal function. No food or fluid is to be given during the night or until 8 a.m. the next day (after voiding), when the regular diet is resumed. The patient is to empty his bladder at exactly 8 a.m. and at the end of each period, as indicated below. The specimens are to be collected for the following periods in properly labeled bottles, as follows: 8 A.M.-10 A.M.; 10 A.M.-12 N. ; 12 N.-2 P.M; 2 P.M.-4 P.M. ; 4 P.M.-6 P.M. ; 6 P.M.-8 P.M.; 8 P.M.-8 A.M. The head nurse will keep a record of the diet and the time of col- lection of the specimens of urine. Each specimen is measured and when cool the specific gravity of it is taken and recorded. Then all of the two hour specimens are put together to make a twelve hour specimen for the day. The total day quantity is determined and the total chlorides are estimated. On the 12 hour night speci- men, measure the quantity, estimate the chlorides, and take the specific gravity. Label each twelve hour specimen, night and day, total quantity, etc., then take to the Metabolism Unit for total nitrogen determi- nations. This is done by the technician in the chemical laboratory. Chart as indicated below. (Normal findings.) TIME OF DAY QUANTITY C.C. SP. GR. SODIUM CHLORIDE TOTAL N. PER CENT GRAMS PER CENT GRAMS 8-10 315 1.006 10-12 128 1.014 12-2 120 1.017 2-4 122 1.020 4-6 76 1.022 6-8 100 1.027 Day Total Output 861 0.78 6.71 0.79 6.80 Night 8 P.M.-8 A.M. 248 1.025 0.69 1.71 1.23 3.05 Day Total Intake 1,760 8.5 13.40 Total Output 1,109 8.42 9.85 Balance 651 10.08 13.55 References: Hedinger, M., and Schlayer, K. R.: Deutsch. Arch. f. klin. Med., 1914, cxiv, 120. Mosenthal, H. O.: Arch. Int. Med., 1915, xvi, 733; ibid., 1918, xxii, 770. 164 METHODS IN MEDICINE A New Method of Interpretation of the Renal Function Test Meal In an attempt to circumvent the interference with the reliability of the interpretations of the specific gravity variations of the two hour specimens and the character of the night urine, suspected from earlier studies to be due to extrarenal factors influencing the fluid supply to the kidney, Sharlit and Lyle attempted to translate renal function findings into terms of urinary solids eliminated. The total solids were calculated as follows: Warm the specimen to about 40° C. so that all urinary solids might go into solution. Cool down to 28° C. and take hydrometric readings. The product of the last two figures of the specific gravity and the volume in cubic centimeters divided by 1,000 and the quotient multiplied by the constant 2.3 (Haeser) or 2.5 (Long) gives approximately the grams of solids present in the given volume of urine. As ratios alone are wanted, the constant multiplier is dispensed with and only the product of the last two figures of the specific gravity and the volume in c.c. is used. The average normal figure was found to be 25. In renal, cardio- renal and cardiac decompensation cases, the urinary solids elimi- nated during the twenty-four hours usually fell well below this figure. The rate of excretion of urinary solids expressed in terms of the ratio of the solids eliminated during the day to that of the night is the first ratio. To this ratio was applied the designation Factor I. The introduction of corrective checks upon Factor I is necessary for the absolute twenty-four hour solids and the volume eliminated, and in a manner to allow for a delay in rate of solid excretion con- sequent upon an increase in total solid output, or reduction in amount of fluid excreted, thus permitting of comparisons between the numerical findings expressive of the rate of excretion in all reactions. These checks are introduced as Factors II and III. „ TT total 24-hour solids Factor II = Factor I x Factor III = Factor II x - total 24-hour volume. This method in interpretation showed that distinctly norma] per- sons with the high protein test meal used, excrete at least twice as RENAL FUNCTION TESTS 165 much urinary solids during the day as during the night with a total twenty-four hour solid elimination in the neighborhood of (25) and a total volume of about 1,500 c.c. so that all Factors I, II, and III produce the numerical equivalent of at least 2. In most cases in which influences might have entered to inter- fere with a normal response to the test meal, the corrective factors apparently operated to produce at least one "factor" numerically equal to 2. For kidneys with defective function either by virtue of renal, cardiac or cardiovascular disease, there is evidenced both a re- duction in the total solids excreted in twenty-four hours and a marked delay in the rate of excretion as estimated in terms of the ratio of day to night elimination of urinary solids. Hence in these cases all three ''factors" of the test meal reaction tend to be numerically below 2; ranging as a rule, about 1 as a mean. The data for these estimations are obtained in doing the reg- ular two hour renal test, observing the same technic throughout as described above, and consequently these factors are additional evidence in the question of the kidney function. Reference: Sharlit, H., and Lyle Wm. G.: Arch. Int. Med., November, 1921, xxiii, 649. Concentration Diuresis Kidney Function Test Observations on the ability of the kidney to secrete a concen- trated and a dilute urine are of importance in estimating the functional condition of the kidney. The following test is devised for that purpose. During the first three-hour period for twelve hours before it, no food or fluid is taken. The specimen passed at the end of this period is there- fore a concentrated urine. During the second three hours, water is forced and a dilute urine is obtained. The success of the test depends upon adhering closely to the following schedule: Schedule 3 p. m. Patient transferred to Metabolism Unit. 6 p. M. Regular diet. Last food and fluid. 6:30 A. M. Next morning, have patient empty his bladder. Throw out urine. Record time to the minute. 9:30 A. M. Have patient void; save the specimen. This represents a three 166 METHODS IN 'MEDICINE hour concentrated specimen of urine. Any specimen voided between 6:30 and 9:30 a. m. should also be saved. Take a 20 c.c. blood specimen in a test tube containing oxalate crystals, for blood chemistry estimations as: nonprotein nitrogen, urea, uric acid, creatinin, etc. 9:30 a. M. Have the patient drink 1000 c.c. of water (not cold). 10:30 A. M. and 11:00 A. M. Have the patient drink 500 c.c. of water at each of these times. Save all specimens voided. 12:30 P. M. Finish the experiment by having the patient empty his bladder. Save the specimen. Use the same accurate timepiece for the whole experiment. 12 :30 p.m. Phthalein Test. One c.c. (6 mgm.) phenolsulphonephthalein is given intramus- cularly at 12:30 p.m., ten minutes are allowed for absorption, and then the urine is collected for the following two hours as per routine, measuring and recording volume outputs at end of first and second hours, as well as estimating the P.S.P. output. The concentration-diuresis test demonstrates two distinct func- tions. First, the ability of the kidney to concentrate the urine during the concentration period. Normal concentration yields a urine with a specific gravity of 1,022 or more in a man, and 1,020 or more in a woman. Fixations of specific gravity below these levels indicate abnormality. The lowest fixation thus far seen in a severe nephritis has been a specific gravity of 1,010. Second, the ability of the kidney to secrete profusely during the diuresis period. With the 2,500 c.c. intake at the end of three hours, a normal man will excrete 1,000 c.c. or more even in warm weather. If the excretion is low or delayed, a cardiac factor must be sus- pected. Cardiac disease would slow the blood flow through the kidney and consequently retard or decrease the diuresis. Reference: Olmsted, W. H., and Day, A. B.: Personal communication, Southern Med. Jour., September, 1922, xv, 677. The blood chemical methods for determining the concentration of nonprotein nitrogen, urea, uric acid and the so-called creatinin, in the blood, as indices of kidney function, are given in Chapter XVII, page 220. RENAL FUNCTION TESTS 167 Method of Search for Hemosiderin in Cells of Urinary Sediment in Hemochromatosis For the Nishimura Test, the fresh sediment, as free as possible from urine, is mixed with a little human serum untinted with hemoglobin and thick films are made and dried. These are fixed by heat, placed in strong ammonium sulphide for one hour, washed briefly with water, and subjected for 20 minutes to a fresh 2 per cent potassium ferrocyanide and 1 per cent hydrochloric acid in equal parts. After another brief rinsing with water the preparations are stained in lithium carmine for a few minutes, differentiated in acid alcohol (1 per cent hydrochloric acid in 95 per cent alcohol) and run rapidly through 95 per cent alcohol, absolute alcohol, and xylol, and mounted in balsam. The acid alcohol differentiates the red of the carmine and turns the iron granules a deep blue. Its action should be carefully followed with the microscope, since if prolonged it will dissolve the iron, or at least cause the blue tint of the latter to run and fade. Nishimura carried out two separate differentiations with acid the first immediately after the ferrocyanide reaction in order to bring out the blue of the iron reaction. But under these condi- tions the subsequent action of the acid tends to destroy the color. A single differentiation is better. Reference: Rous, Peyton: Jour. Exper. Med., November, 1918, xxviii, No. 5, pp. G29, 645. CHAPTER XV STANDARDIZATION OF HEMOGLOBINOMETERS For general use the Sahli Hemometer, when standardized at intervals of a month, and kept in the dark when not in use, and when a few important principles are observed when estimations are made, gives fairly accurate results as to the percentage of hemoglobin in the given blood specimen. The pipettes must always be restandardized with mercury or water to contain exactly 20 c.mm. The mark of 20 c.mm. level should be a ring around the pipette rather than a line, as the bottom meniscus can be more accurately leveled to the ring. The graduated test tubes must likewise be checked with mer- cury or water, to contain exactly 20 c.mm. for each percentage level up to the 100 per cent ring equaling 2 c.c. The standard solution should be contained in a tube of exactly similar bore as the test tube and should contain exactly 2 c.c. of 100 per cent acid hematin solution or suspension in glycerin and water. The preparation of a standard acid hematin solution that will be more or less permanent has always been a problem. The oxygen capacity method of Van Slyke1 (See Chapter on Physiological Chemistry) for standardization is most convenient and satisfac- tory, as the oxygen capacity of blood depends upon its hemoglobin content. Haldane's standard of a 1 per cent solution of blood hav- ing an oxygen capacity of 18.5 per cent is too low for this coun- try. A blood of 18.5 per cent oxygen capacity contains approx- imately 14 gm. of hemoglobin per 100 c.c. The average normal blood of healthy men in this country has an oxygen capacity of 22 per cent and contains on the average 16.6 gm. of hemoglobin per 100 c.c. Haldane's standard is accepted by Palmer2 as the basis for his carbon monoxide oxyhemoglobin determination method. This would make about 110 per cent the normal level of hemoglobin in this country unless, of course, the rational basis of expressing hemoglobin in grams per 100 c.c. of blood be accepted, and the 168 STANDARDIZATION OF HEMOGLOBINOMETERS 169 normal amounts for each age in either sex be determined. However, as long as the more or less arbitrary way of expressing hemoglobin in percentage remains, it seems advisable to use the American standard of oxygen capacity 22 per cent and hemoglobin content 16.6 gm. per 100 c.c. as the 100 per cent standard. A standard acid hematin solution can be prepared by taking a quantity of defibrinated human blood from a group of 5 or 10 healthy young male adults and determining the oxygen capacity by the method of Van Slyke.1 The blood may also be standardized by a spectrophotometer in the hands of an expert, or solutions made from hemoglobin crystals prepared according to the method of Butterfield.3 The standardized blood is diluted with 0.1 N. hydrochloric acid so as to make a 20 per cent stock acid hematin solution of a blood with an oxygen capacity of 22 per cent and a hemoglobin content of 16.6 gm. per 100 c.c. This standard stock solution remains constant for six months if kept sealed in a glass ground stoppered dark glass or amber bottle in an ice chest. The 1 per cent standard for routine use is made up by taking exactly 1 c.c. of this 20 per cent standard acid hematin solution and diluting it to exactly 20 c.c. with 0.1 N. hydrochloric acid or distilled water. Exactly 2 c.c. of this solution are placed in a tube of the same diameter and thickness as the graduated tube and sealed hermetically or with cork and paraffin. The rest of the diluted standard may be kept sealed in a dark bottle on ice. The standard in the 2 c.c. tube of the Sahli apparatus, if protected from light remains unchanged for from two to four weeks. Jacobson4 advocates the use of a permanent rufigallic acid solu- tion instead of the standard acid hematin solution. The rufigallic acid is standardized against the standard acid hematin just as an unknown acid hematin solution is estimated against the standard except that it is advisable to use the Duboscq colorimeter in this determination. The substitution, for a standard hematin hydrochloride solution, of a solution of greater color-fastness and identical color is the reason for the rufigallic acid procedure. Gallic acid, C7HGO5, when treated with sulphuric acid assumes a deep brown color. Tannic acid, C14H10O9, which is 2 molecules of gallic acid minus 1 molecule of water, when dissolved in water and exposed to the action of 170 METHODS IN MEDICINE oxidizing agents or molds is changed to a similar brown color. These solutions, compared with one of acid hematin, are of identical color, both to the naked eye and in the chambers of a Duboscq colorimeter. While kept in a clean, stoppered container (not pri- marily sterile), with a drop of 95 per cent phenol for each 20 c.c., the color intensity has been found to remain constant for ten months, even when exposed in a sunlit window, while one of the Sahli's acid hematin tubes faded markedly in three days and was colorless in a week. One hundred c.c. of a 20 per cent aqueous solution of tannic acid or a 1 per cent solution of gallic acid, either one of which, after the addition of from 5 to 10 drops of concentrated sulphuric acid, to- gether with gentle heating for a minute, gives a deep brown col- ored solution which reaches maximal intensity of color after about two hours. This solution can be diluted to any desired strength. Gallic acid treated with sulphuric acid produces rufigallic acid (hexa-oxyanthrachinon) of a brown color. Tannic acid in the pres- ence of dilute acids, both organic and inorganic, produces gallic acid. This gallic acid, or the gallic acid which always is present in tannic acid, is changed by sunlight and dilute organic acids to rufigallic acid. Therefore, the brown color in tannic acid is due to the formation of rufigallic acid. Utilizing this similarity of color, standard tubes of "rufigallic acid" have been prepared. There are various methods of making a "standard" solution: A 1 per cent solution of blood from each of a group of normal individuals can be mixed together and the composite sample called "average normal"; or, a 1 per cent solu- tion of blood from a robust young adult with a high normal erythro- cyte count can be called "high normal," and the readings of other normal persons being from ten to twenty points lower an "average normal" for that solution can be estimated, such a figure being the one always used in computing the color index. Comparison with Palmer's carbon monoxide method is probably the best way to standardize the solution. References: iVan Slyke, D. D., and Stadie, Wm.: Jour. Biol. Chem., 1921, xlix, 1. zPalmer, W. W.: Jour. Biol. Chem., 1918, xxxiii, 119. 3Butterfield, E. E.: Z. Physiol. Chem., 1909, Ixii, 173. 4Jacobson, V. C.: Jour. Am. Med. Assn., Oct., 1919, Ixxiii, 1282. 171 STANDARDIZATION OF HEMOGLOBINOMETERS Notes,-Meulengracht has pointed out a number of sources of er- ror in the actual estimation of the hemoglobin percentage by the comparison of the unknown acid hematin solution with the standard. The increasing intensity of color described by Staubli was shown to increase the hemoglobin 25 per cent after ten minutes as com- pared with the estimation within one minute. The curve of rise is very steep during the first few minutes and then becomes fairly flat. It is therefore necessary to fix exactly the time in which the dilution is made and at which the colorimeter is to be read. This has been done and Sahli states that the reading with his apparatus is to be made one minute after the dilution while with the Hellige apparatus the reading time is fixed at ten minutes. The increasing intensity of color is furthermore dependent upon the mass of hemoglobin, the hydrochloric acid concentration and the temperature. All of these factors must therefore be fixed and constant in order to obtain reliable results. Reference: Meulengracht, E.: Folia Hematologica, xxvii, No. 1, p. 1. Dr. E. H. Terrill5 has ingeniously produced stable hemoglobin standards of the highest grade. These promise to solve the prob- lem of practical accurate hemoglobin estimations. Production of Stock Solutions of Acid Hematin A volume (usually 100 to 500 c.c.) of defibrinated or oxalated blood is centrifuged and the plasma removed. Sufficient water is added for taking, and HC1 to a concentration of 1/10 N to produce the acid hem- atin. Twenty-four hours are allowed for the full development of color in the acid hematin solution, at room temperature. This turbid solution of 7 to 12 per cent concentration is clarified by repeated filtration through hardened papers. Further concentration is ac- complished by evaporation, with the aid of an electric fan, from a shallow dish in a comparatively dust-free atmosphere. When, after several hours, the solution has become syrupy, filtration by suction is done. The process is continued until the solution is so thick that it can just be pipetted, which is 15 to 2'0 per cent ac- cording to Haldane's scale The concentration of this stock solution is calculated by comparing a known dilution of it to a known acid hematin solution. The stock solution is diluted to any convenient 172 METHODS IN MEDICINE figure above 15 per cent and accurately measured into 2 c.c. amber glass ampules. Standards'for colorimetric work are made from these ampules by dilutions with distilled water and 10 to 20 per cent glycerol, usually corresponding to 10 gm. of hemoglobin per 100 c.c. The glycerol prevents sedimentation and bacterial growth. Production of Stock Dry Powder of Acid Hematin Protein A volume, usually 500 c.c., of defibrinated or oxalated blood is centrifuged and the serum removed and the cells rewashed four times with normal saline solution. To the washed cells are added an equal volume of distilled water and sufficient ether to produce complete laking. After thorough shaking allow to stand for ten minutes; if very viscid, dilute slightly with distilled water; then filter or centrifuge to remove the stroma of the red cells. The protein is removed from the clear dark-red filtrate by suction, filtration, or, preferably, centrifugalization following precipitation by an equal volume of aluminium cream. The aluminium cream is prepared according to Tracy and Welker, by adding a slight excess of a 1 per cent solution of ammonium hydroxide to a 1 per cent solution of ammonium alum at room temperature. The precipi- tated cream is washed by decantation until the wash water shows the faintest trace of residue on evaporation. Small portions of alcohol are added, with constant shaking, un- til it is present in a concentration of 20 per cent. Any precipitate, or even the slight turbidity which is almost inevitable, should be removed preferably by nonsuction filtration through hardened paper. Complete saturation of the hemoglobin is accomplished by oxy- gen or air bubbling through the solution. A half volume of 0.25 N hydrochloric acid is added in small amounts with constant shak- ing. A clear, perfectly dark, sometimes syrupy product results. At least 24 hours are allowed for complete or full color develop- ment. No warming should be instituted. Concentration is again accomplished by evaporation with a fan. Evaporation may be sped up by using greatly reduced pressure over phosphorus pentoxide. When the solution becomes syrupy, filter through a hardened paper. Carry evaporation out to dryness of the product. When thoroughly dry, powder and mix thoroughly in order to insure homogenicity and facilitate solution. The yield STANDARDIZATION OF HEMOGLOBINOMETERS 173 from 500 c.c. of blood is about 40 gm. of acid hematin protein; a dark brown, hard, brittle, vitreous mass which is stable in air and, when perfectly dry unaffected by dry heat of 100° C. for several hours. It is rather easily soluble in distilled water, but much less so in 1/10 N hydrochloric acid. The solution is perfectly clear and exactly matches a freshly prepared acid hematin solution. Weighed amounts of the powder can be sealed in ampules. The standardization of the powder is carried out by dissolving carefully weighed portions (30 to 50 mg.) in sufficient water to make a solution containing 2 mg. per c.c. and then adding an equal volume of accurate 2/10 N hydrochloric acid; allow to stand for an hour. Read against a solution of known strength made from previously laked blood. From this calculate the number of mg. of the powder per c.c. required to give any desired strength. Standard solutions are prepared by weighing the powder to 0.1 mg. and the required volume of solvent calculated. The powder is completely dissolved in half this volume of 20 to 40 per cent glycerol, after which the other half of the volume is made up with accurate 0.2 N hydrochloric acid. Allow to stand for an hour, and keep in tightly stoppered brown glass bottles. Acid hematin films to be used as Newcomer's colored glass plate can be made from concentrated aqueous 1/10 N HC1 acid hematin solution and moderately thick gelatin and poured bubble-free on cover slips. Procedure for Hemoglobin Determinations A pipette containing 50 c.mm., which can easily be filled from a finger prick, has been found most suitable. This is filled, the blood thoroughly mixed with 5 c.c. of distilled water in an accurate 10 c.c. graduate, and the pipette rinsed. After standing % min- ute to insure complete laking 0.2' N hydrochloric acid is added to the 10 c.c. mark, making a 0.5 per cent solution of acid hematin. Note the time. After standing 10 to 15 minutes it may be read. To read, the unknown is placed on the left side of the Duboscq colorimeter and set at 20 mm., the readings being made with the standard. Ordinarily a liquid standard is preferred to the gelatin film, since it permits the use of any desired depth of color. A solution corresponding to 10 gm. of hemoglobin per 100 c.c. has been found 174 METHODS IN MEDICINE most desirable, for when the unknown is made up as a 0.5 per cent solution as above described, and set at 20 mm., readings being made with the standard, the depth of the latter in mm. is equal to the number of grams of hemoglobin per 100 c.c. of the unknown blood. Corrections may then be made from Newcomer's equation (xy equals -C, where x equals the time in minutes since the addition of the acid; y equals 100, the percentage of color developed; -C equals 40). Reference: Terrill, E. H.: Jour. Biol. Cliem., July, 1922, liii, 179. The Carbon Monoxide Method for the Colorimetric Determination of Hemoglobin The advantages of this method as outlined by Palmer are that there is no difficult technic and no extra, and otherwise useless, ex- pensive apparatus necessary. The method is rapid, accurate and universally standard for the estimation of hemoglobin. The standard hemoglobin solution is made up by Palmer accord- ing to Haldane's standard of a blood of 18.5 per cent oxygen ca- pacity containing approximately 14 gm. of hemoglobin per 100 c.c. The American standard corresponding to an oxygen capacity of about 22 per cent and a hemoglobin content of 16.6 gm. would seem to be a more logical basis for percentage estimation in this country, as about 110 per cent must be considered as normal when the standard is made up according to Haldane's figures. A quantity of defibrinated human or ox blood is obtained and the oxygen capacity determined according to the modified method of Van Slyke (see Chapter XIV). The blood is diluted with 0.4 per cent ammonia solution (4 c.c. of strong ammonia in 1000 c.c. solu- tion) so as to make a 20 per cent solution of a blood with an oxy- gen capacity of 18.5 per cent. A drop of caprylic alcohol is added and then illuminating gas is bubbled through this 20 per cent blood solution until it is satu- rated with carbon monoxide. The glass delivery tube through which the gas is passed is slowly withdrawn and the bottle stoppered with a cork (never rubber) stopper and paraffined. This stock solution in a dark bottle, covered with a black opaque paint or paper, kept in an ice chest will remain unchanged for a year. The 1 per cent standard for use in the colorimeter should be pre- pared fresh every two to three weeks. This 1 per cent standard for STANDARDIZATION OF HEMOGLOBINOMETERS 175 routine use should be kept as cool as possible in a dark glass or black painted aspirator bottle, the lower opening of which is provided with a cork through which passes a glass tube with a ground glass cock for withdrawing small amounts of solution. A glass tube is put through the cork in the top of the bottle and extends to the bottom. The corks should be sealed with paraffin. The tube through the top is connected with an open gas fixture so that gas rather than air will enter to replace the solution drawn from the bottom. Pipettes are made from straight millimeter tubing; the points are rounded off on an emery wheel. The tubes are calibrated to contain 0.05 c.c. and 0.10 c.c. with water or mercury. Calibrated pipettes obtained from laboratory supply houses must be recali- brated before they can be relied upon. Method.-Blood to be tested is obtained by a clean pricking of the finger or the lobe of the ear, producing a free flow without the use of any milking of the part. A 1 per cent solution of blood is made by drawing 0.05 c.c. into the special pipette and transferring it into a 12 x 120 mm. test tube containing exactly 5 c.c. (accurately measured with a calibrated pipette or burette) of 0.4 per cent ammonia solution (4 c.c. of strong ammonia in 1000 c.c. of water) which causes the full color of car- bon monoxide hemoglobin to develop at once. The pipette is rinsed by drawing the carefully measured ammonia solution into it two or three times. Ordinary illuminating gas is bubbled rapidly through the am- monia blood solution for thirty seconds. After this the unknown carbon monoxide solution is compared with a standard carbon monoxide hemoglobin solution in a Duboscq colorimeter set at 10. The average of at least four readings is taken and the simple cal- culation made according to the x 100 = % hemoglobin. Color comparisons are most accurate when the unknown hemo- globin solution reading falls between 9 and 11 on the colorimeter scale. If the reading falls below 8 or above 12, another sample must be taken and the dilution made so that the reading falls be- tween 9 and 11. The amounts of blood and ammonia solution may be easily varied and the necessary corrections in the colorim- eter and calculations made. Reference: Palmer. W. W.: Jour. Biol. Chem., 1918, xxxiii, 119. 176 METHODS IN MEDICINE BLOOD GROUPING The microscopic methods of grouping of blood give the more relia- ble results and are therefore recommended. Besides the micro- scope, hollow ground hanging drop slides, cover-slips, a platinum or nichrome loop, a few small test tubes and a solution of 2 per cent sodium citrate preferably in normal 0.9 per cent saline are needed. Known stock serums of Group II and Group III should be kept on hand in an ice chest. It is also advisable to have fresh red cell suspensions of Group II and Group III. The unknown blood may be obtained by a stab, as in the proce- dure for the routine examination of the blood, but it is preferable to collect it by puncturing the vein, as in the study of the coagu- lation time, etc. Three or 4 drops of blood are added to a small test tube containing about 5 or 10 c.c. of the 2 per cent sodium citrate saline solution to make a thin suspension of cells. One or 2 c.c. of blood are collected in a small dry test tube and centrifuged or allowed to stand until the serum is separated. In the Moss method the red cell suspension of the unknown alone is used. Two loopfuls of the known Group II serum are placed on one cover-slip and two loopfuls of the known Group III serum are placed on another cover-slip. To each one of these serums is added one loopful of the unknown cells, and after ringing with vaseline hanging drop preparations are made. The preparations are rotated, so as to mix the serum and cells, and examined under the micro- scope within a minute or two for evidence of agglutination. In the presence of agglutinins clumping begins immediately. Rouleau formation, which may be especially prominent when the red cell suspension is not thin, must not be mistaken for agglutination. If the unknown is Group I, there will be agglutination with the serum of Group II and Group III. If the unknown is Group II, there will be agglutination with the serum of Group III but none with Group II. If the unknown is Group III, there will be agglutination with the serum of Group II but none with Group III. If the unknown is Group IV, there will be no agglutination with the serum of either Group II or Group III. Group II and Group III serums dried on cover-slips can be obtained from laboratories where stock serums are on hand, and BLOOD GROUPING 177 furthermore serums of Group II and Group III may be preserved for a long time when kept in an ice chest. Red cell suspensions autolyze within a few days. However, it is always well to check results by the other method and verify by matching. In this connection the modification of Brem is of advantage in giving a clear cut reaction when fresh red cell suspension as well as serum of either Group II or Group III, preferably the latter, are obtainable. On one cover-slip mix two loopfuls of the unknown serum and one loopful of the known red cell suspension and make a hanging drop preparation. Two loopfuls of the known serum and one loopful of the unknown red cell suspension are mixed on another cover-slip to make the second hanging drop. Group III blood is preferable as the numbers of persons in this group are so few that consequently there is only rarely no agglutination on either side. If the Group III serum agglutinates the unknown cells, the un- known must be in either Group I or Group II. If the Group III cells are agglutinated by the unknown serum, the unknown is Group II. If the Group III cells are not agglutinated by the unknown se- rum while the Group III serum agglutinates the unknown cells, the unknown is in Group I. If Group III serum does not agglutinate the unknown cells the unknown must be in either Group III or Group IV. If the Group III cells are agglutinated by the unknown serum the unknown is Group IV. If the group III cells are not agglutinated by the un- known serum while Group III serum does not agglutinate the un- known cells, the unknown is in Group III. If Group II serum and cells are used with the unknown cells and serum, the agglutination in both preparations means that the un- known is Group III while the agglutination in neither preparation signifies that the unknown is in Group II. If the known cells are agglutinated by the unknown serum while the unknown cells are not agglutinated by the known serum we have Group IV. While if the unknown cells are agglutinated by the Group II serum and the known cells are not agglutinated by the unknown serum we have Group I in the unknown. 178 METHODS IN MEDICINE The figure in which - means no agglutination and + means agglutination may serve to fix graphically the interaction of the blood groups. The negative diagonal, forming the hypotenuse of the negative left lower right angle triangle, with the one plus in the center, and all other spaces 4-, are distinctive features. Guthrie and I have discovered other groups. References: Moss, W. L.: Johns Hopkins Hosp. Bull., 1910, xxi, 63. Brem, W. V.: Jour. Am. Med. Assn., 1916, Ixvii, 190. Sanford, A. H.: Jour. Am. Med. Assn., 1918, Ixx, 1221. Cells I II Sera III IV I - + + 1 + I II - - + + III - + - + IV - - - - - Estimation of the Coagulation Time of Blood Modifications of Minot and Lee Blood is obtained by a quick, neat vein puncture, preferably through a paraffined needle attached to a small paraffined cylinder with a stopcock between. Trauma is minimized by this method, but only single observations are possible from the vein puncture. The more practical way is to use scrupulously clean, smooth and sterile needles, syringes and standard test tubes, 8 mm. in diam- eter. About 5 c.c. of blood are carefully and quickly withdrawn from a vein which has been penetrated with the least possible trauma. One cubic centimeter of blood is transferred as neatly as possible to each one of five standard 8 mm. test tubes which have been just previously slightly moistened wfith normal salt solution and kept at a uniform temperature of 23° C. After exactly five minutes from the time the blood appeared in the syringe the first tube is gently tilted and at two minute inter- vals each succeeding tube is gently tilted and the time is deter- mined as the fluidity becomes less and the end point is approached. Note the time at which the first sign of coagulation appears, as well as the end point at which the tube can be inverted without spilling, which surface coagulation alone prevents. It is of inter- est to note how much longer it takes for complete coagulation. The longest time that it takes the blood to coagulate in any one tube to the point of not spilling on inversion of the tube or the average time in the different tubes may be considered the coagu- lation time. Normally the coagulation time is from six to twelve minutes. SPECIAL BLOOD STUDY METHODS 179 The time from this end point of surface coagulation to complete solidification is from two to three minutes, complete coagulation is considered to have taken place when after jarring the inverted tube, no fluid blood appears. The character, firmness, toughness and retractility of the clot are to be noted. References: Lee, R. I., and White, P. D.: Am. Jour. Med. Sc., 1913, cxlv, 495. Minot, G. R.: Jour. Med. Research (N.S.), 1918, xxxviii, 503. Bleeding Time Estimations The skin of the lobe of the ear is punctured with a sharp needle. A smooth, medium-sized puncture is preferable. No pressure is to be exerted on the part; neither is it to be massaged at any time during the test. The drops that exude are completely but neatly and gently wiped away with blotting paper or absorbent cotton at half min- ute intervals. The drops can then be counted and the time esti- mated. Normally the hemorrhage should cease in two and one-half to three minutes. Reference: Duke, W. W.: Arch. Int. Med., 1912, x, 445. Blood Platelet Counting The use of 3 per cent sodium citrate as a diluting fluid is a sim- ple and satisfactory method for the counting of platelets and at the same time the red blood cells. The blood is diluted in the red cell counting pipette in exactly the same way as in making the ordinary red cell count. The blood is then allowed to stand in the counting chamber for ten minutes at least in order that the blood platelets which are of relatively low specific gravity, may have time to settle down to the surface of the ruled area. They are counted with a high power lens in the same manner as red blood cells, except that on account of their relative scarcity about ten times as many squares must be counted. The normal platelet count varies from 200,000 to 400,000 per cubic millimeter. Reductions below 50,000 are practically always accompanied by purpura. 180 METHODS IN MEDICINE An estimation of the number of platelets may be made from the smears stained with Wright's or preferably brilliant cresyl blue or crystal violet on an unfixed fresh blood smear. Reference: Ottenberg, R., and Rosenthal, N.: Jour. Am. Med. Assn., 1917, Ixix, 999. To summarize the criteria obtained from these three blood tests in the diagnosis of the forms of hemorrhagic disease: In purpura hemorrhagica the coagulation time is normal, the bleeding time greatly prolonged and the platelets greatly decreased. In purpura secondary to jaundice, chloroform or phosphorus poisoning coagu- lation and bleeding time are prolonged, while in that of scurvy both of these together with the platelet count are normal. In pur- pura simplex, arthritic or visceral purpura, all three tests show normal findings. In hemorrhage of the new born the blood coagu- lation is greatly prolonged and the bleeding time is prolonged. In hemophilia, the coagulation time is enormously prolonged while the bleeding time is normal or prolonged and the platelet count is normal. The Fragility Test for Erythrocytes The stock, solution is made by dissolving 0.5 gm. sodium chloride (c.p. and anhydrous) in 100 c.c. distilled water. Great care should be exercised in making this solution. A delicate balance should be used for weighing and a volumetric flask for measuring. A twelve-hole test tube rack, with at least two rows of holes, is filled with 3 in. x % in- tubes. The front row is for the patient's test, the back row for a con- trol of normal erythrocytes from the examiner. The tubes in the front row are numbered with a glass marking pencil: 25, 24, 23, 22, 21, 20, 18, 17, 16, 15 and 14. In each tube in the front row, and in the tube in the back row immediately behind it, is placed the number of drops of 0.5 per cent salt solution indicated by the figure marked on the tube in the front row. A capillary pipette drawn from soft glass tubing is used for putting the drops of salt solution into the tubes. With the same pipette distilled water is added drop by drop to each tube so that there is a total of 25 drops of fluid in each tube in both rows. For example, a tube marked "20" should contain SPECIAL BLOOD STUDY METHODS 181 20 drops of 0.5 per cent NaCl solution and 5 drops of distilled H2O and the control tube behind it should contain the same. The patient is bled by puncturing the vein in the usual manner employed in obtaining blood for the Wassermann test. A rather small gauge needle should be used and there should be no delay in getting the blood. An all-glass syringe, sterilized by boiling and thoroughly dried, should be used. It is not necessary to rinse out the syringe barrel, and the use of a normal saline solution is not advisable, as in this way an excess of salt might be added to the solution in the tubes. One drop of blood should be allowed to fall into each tube in the front row. The tube should be thoroughly shaken to make an immediate corpuscle suspension. In the back row (or the control tubes) should be placed blood ob- tained in a similar manner from the normal person. The tubes are allowed to stand an hour or two at room tempera- ture and the results are then read. The dilution in which there is just a slight tingeing of the super- natant fluid due to taking of a few of the least resistant corpuscles is noted as the point of initial hemolysis. Reading from left to right the first tube in which it can be demonstrated that the hemo- globin is entirely free and that there is no corpuscular residue evi- dent by shaking the tube, indicates the point of complete hemolysis. The percentage of NaCl solution indicative of initial and com- plete hemolysis is readily reckoned as follows: Tube "20" showing initial hemolysis contains 20/25 of 0.5% NaCl = 0.40% NaCl. Tube "16" showing complete hemolysis contains 16/25 of 0.5% NaCl = 0.32% NaCl. The percentage can be immediately determined by multiplying the number on the tube by 0.02. Normal blood shows beginning hemolysis in 0.42 per cent to 0.32 per cent NaCl solution. "An increase in fragility" is present when initial and complete hemolysis occurs in solutions stronger than normal. "An increase in resistance" is present when initial and complete hemolysis occurs in solutions weaker than those which lake normal blood. 182 METHODS IN MEDICINE Ilemolytic jaundice shows initial hemolysis .46 per cent to .50 per cent and complete hemolysis .40 per cent to .46 per cent. Reference: Giffin, H. Z., and Sanford, A. H.: Jour. Lab. and Clin. Med., May, 1919, iv, 465. Vital Staining The estimation of the hematopoietic activity of the bone mar- row, an index of which we have in the reticulated red cel], is es- sential in the differential diagnosis of certain disease manifesting blood changes, as well as in evaluating therapeutic measures. The normal proportion of reticulated red cells to nonreticulated cells in the adult is 2 per cent and more, while in Banti's disease there is practically an absence of reticulated red cells. In severe pernicious anemia with an actively regenerating hyperplastic red bone marrow the percentage often reaches 20 per cent while in aplastic anemia there is, on the contrary, almost always an absence of reticulated cells. Reticulation, like polychromatophilia and probably some forms of stippling, are the evidences of the youth of the red blood cells. Reticulation of the red cells can be estimated in the fresh state by mixing a drop of freshly drawn blood and an equal amount of a vital stain, such as a filtered saturated aqueous, normal saline or alcoholic solution of brilliant cresyl-blue. The edge of the cover- slip upon which the two drops of the mixture are held, is ringed with vaseline, inverted on a slide and sealed. Observations are then made with the oil immersion lens. Permanent preparations are made by the technic of Vogel and McCurdy. A saturated normal saline solution (0.85 per cent NaCl) of brilliant cresyl blue is filtered through double paper and centri- fugalized to remove all particles. The following mixture is freshly prepared and filtered: 1. Sodium oxalate solution (2 per cent), 2 c.c. 2. Normal saline (0.85 per cent NaCl) 5 c.c. Add 1 to 2 and then mix with 5 c.c. the following stain. 3. Brilliant cresyl blue, (saturated solution in 0.85 per cent NaCl) and filter. Blood is drawn as for the red blood count and the above mix- ture used as a diluent. Mix and allow the stain to act for 10 min- SPECIAL BLOOD STUDY METHODS 183 utes. Blow the contents of the diluting pipette into a centrifuge tube and centrifugalize. Draw off the diluting and staining fluid with a capillary pipette. The remaining sediment of cells is re- moved from the bottom of the centrifuge tube in another capillary pipette; a drop is placed on a clean flamed cover-slip or slide for spreading and drying as in the making of ordinary blood-smears. These dried smears mounted in neutral balsam and kept in the dark remain permanent indefinitely. Great assistance in counting the cells is afforded by the use of an Ehrlich eye piece or an improvised substitute in the form of a black cardboard disk with a centrally cut 8 mm. square hole for dropping over the diaphragm of the ordinary eyepiece. Hawes and more recently Cunningham have added to the above procedure the counter staining with Wright's stain thus making the single smear serve a double purpose. The technic is varied somewhat. A small drop of 0.3 per cent or 0.5 per cent aqueous or alcoholic solution of brilliant cresyl blue is smeared with a match stick or glass rod over an area 1.5 c.m. in diameter in the center of a clean cover-slip or at the end of a slide. After drying, the margin of thick stain should be wiped off with a damp cloth. Cover glasses and slides can be prepared in this way and kept in stock. A drop of blood is taken on a clean cover glass and dropped on one of the uniform areas of dried stain. The instantaneous solution of the stain and the clean cover glasses allow the rapid spread to the edges and the glasses are pulled apart and air dried. The preparations are then stained with Wright's in the ordinary way. The blood in the more severe anemias gives the better results in this technic, while the more normal bloods may give difficulty, therefore a number of preparations should be made and not a single one or two depended upon. The reticulum may be heavy deep blue skein-like material or knotted granular particles separate or connected by delicate light blue threads. No polychromatophilia can be seen. References: Hawes, J. B.: Boston Med. and Surg. Jour., 1909, clxi, 493. Vogel, K. M., and McCurdy, U. F.: Arch. Int. Med., 1913, xii, 707. Cunningham, T. D.: Arch. Tut. Med., 1920, xxvi, 405. 184 METHODS IN MEDICINE Oxidase Reaction Staining Granules of Myelocytes Graham's First Method 1. Fix Blood Smear 1-2 min. ih a mixture of R 9 parts of 95% Alcohol. 1 part of 40% Formaldehyde. (This mixture must be freshly prepared.) 2. Wash in Water and Flood with Alphanaphthol solution for 4-5 min. R Alphanaphthol 1 gm. or % gm. Merck's "Recrystallized" (250 mg.) 40% Alcohol 100 c.c. or 25 c.c. Merck's "Reagent" Hydrogen Perox. 0.2 or 0.05 c.c. Allow a Reaction Time of 4-5 min. 3. Wash, and place in a dish of running water for 15 min. (Dry in air.) 4. Stain 2 min. with Pyronin Solution: R Pyronin 0.1 gm. Anilin 4 c.c. 40% Alcohol 96 c.c. Dissolve pyronin in the alcohol and add the anilin. The solution keeps well. 5. Wash in water. 6. Stain % to 1 min. with 0.5 per cent aqueous solution of methyl- ene blue (Grueblers B.X.). 7. Wash in water; blot dry. Cover-slip preparations are mounted in balsam. Smears should be made on the slide by touching the slide used as a spreader to the periphery of the drop of blood and allowing the film to follow the spreader as the latter is slowly moved away. When stain is dry add balsam and a cover-slip to the slide. Balsam should be neutral. If acid, the granular stain fades. An acid stain may be neutralized. The Resulting Picture is much like that afforded by the Roman- owski Stain, except for greater prominence of the granules. The neutrophilic granules are usually very abundant so that the cyto- plasmic substance of the cell appears almost completely filled with SPECIAL BLOOD STUDY METHODS 185 them. They are somewhat irregular in form and size and are purplish red in color. Occasional cells show fewer and more faintly stained granules. They may represent old degenerating forms of the cell. The eosinophilic granules are larger, somewhat lighter and more refractive and have the appearance of spherical bodies with lighter staining centers. The Mast cell basophilic granules take a more basic stain so that they appear as deep purple colored bodies. Myelocytes have granules of varying number and size. Erythrocytes are greenish yellow to pink. Platelets are blue. Nuclei of all cells blue; cytoplasm light blue. Reference: Graham, G. S.: Jour. Med. Research, (N. S.) 1916, xxxv, 231. A Peroxidase Reaction with Sodium Nitroprusside and Benzidine in Blood Smears Goodpasture's Technic The first method proposed by Graham was an adaptation of the well-known peroxidase reagent alphanaphthol with a counterstain of pyronin, two chemicals which are scarcely available. For this reason Graham undertook experiments with other peroxidase sub- stances, with the result that he has advocated the use of benzidine which gives more satisfactory results than previous investigators had obtained. The technic is simpler than that of the alphanaph- thol process, though the brown color reaction is not very striking or clean cut. The following method for demonstrating the perox- idase reaction in leucocytes on smears and in sections involves a chemical test, depending upon a color reaction with sodium nitro- prusside. The reagents and counterstain are prepared in a single stock solution of the following composition: Alcohol 95 per cent 100. c.c. Sodium nitroprusside .05 gm. Benzidine (C.P.) (Harmer) .05 gm. Basic fuchsin .05 gm. In the diluting water add 1 drop of 3 per cent H2O2 (fresh) for each 50 c.c. 186 METHODS IN MEDICINE The sodium nitroprusside is dissolved in as little water as possi- ble (1 or 2 c.c.) and added to the alcohol; the other ingredients are then included. The stock reagent after some weeks has shown no deterioration in activity, although a slight flocculent precipitate set- tles out in a few days. Technic for Smear Preparations Fresh smears of blood or other cellular material are permitted to dry thoroughly on the slide. The reagent is dropped upon it in sufficient quantity to cover the smear which is then allowed to fix for one minute. An equal quantity of water containing the minute amount of H2O2 is added. A reaction time of three minutes has been found sufficient. The preparation is finally washed out with water and dried by blotting. The neutrophilic granules of polymorphonuclear leucocytes are stained deeply blue and are sharply defined. Eosinophilic granules are dark blue about their periphery with a light center. Basophilic granules do not seem to react. Fairly numerous and sharply de- fined granules are stained in the so-called transitional cells and also in certain mononuclear cells of doubtful classification which with the usual stains would probably be grouped with lymphocytes. Most mononuclear cells show no reaction. Nuclei are stained a clear red, cytoplasm and platelets pink, and red blood corpuscles a smooth buff color. Altogether there is a sharp and pleasant contrast. References: Goodpasture, E. W.: Jour. Lab. and Clin. Med., 1919, iv, 442. Method of Concentrating Malaria Plasmodia Bass and Johns' Technic Material required. (In charge of Assistant Resident in Bacte- riology.) 1. A solution of 50 gm. sodium citrate and 50 gm. dextrose in sufficient distilled water to make a volume of 100 c.c. Solution is aided by heat. Filter. Apparatus required. (In charge of Assistant Resident in Bacte- riology.) SPECIAL BLOOD STUDY METHODS 187 1. All glass syringe, capacity 10 c.c. 2. A 1 c.c. pipette, graduated in hundredths. 3. Plain test tubes (centrifuge tubes) 1 to 5 cm. inside x about 12 cm. Cornell centrifuge shields are necessary for these round bot- tom tubes. The conical centrifuge outfit should be used. 4. Plain test tubes 5 mm. inside x about 12 cm. These can be made out of suitable tubing. 5. Capillary pipettes, large size. Inside diameter of capillary should be about 1 mm. These are made of suitable glass tubing. 6. Capillary pipettes small size. Outside diameter of tube should be less than inside diameter of large capillaries. These are made of suitable glass tubing. 7. Rubber nipple. 8. Glass cutting knife or file. 9. Electric centrifuge having speed of 2000 or more R.P.M. 10. Clean glass slides; Wright's stain; fresh balsam; clean cover slips and microscope with oil immersion and cedar oil. Method.-Measure 0.2 c.c. of the citrate-dextrose solution into a large tube. Draw 10 c.c. of the blood with the syringe from a vein in the usual way and mix it with the citrate-dextrose solution at once by revolving or shaking the tube. Place approximately equal quantities of the citrate-dextrose solu- tion in two of the large centrifuge tubes. The depth of the col- umn in the tube may vary from 2 to 5 cm. Centrifuge both tubes for the proper length of time. For 18 cm. arm and 2500 R.P.M., one minute for each cm. of the column of blood. All the plasmodia (except the small estivo-autumnal rings) and the leucocytes rise to the top of the cell sediment and are in the first millimeter. With a large pipette skim off as much as you can of this layer from each tube and place in one (or two) of the 5 mm. tubes and mix thoroughly. The column in the small tube must not be deeper than 5 cm. Centrifuge as before. Now with the large capillary, draw not more than a 5 cm. column of cells into it from the surface of the cell and blow it out of the pipette against the surface of the slide. Draw it up into the pipette past the tip and seal the end of the pipette in a flame. Cut off the part of the capillary containing the blood and centrifuge as before. 188 METHODS IN MEDICINE After centrifuging, there will be found a small amount of gray- ish leucocyte mass merging into the column of erythrocytes. In very heavy infections, the lower part of the leucocyte layer and the upper part of the erythrocyte column have a brownish appearance from the pigment and present the large amount of plasmodia here. Cut the capillary at a point about 1 mm. to 2 mm. below the bot- tom of the leucocyte layer and with a smaller capillary draw out the small amount of erythrocytes and leucocytes and a little plasma for dilution. Mix and make one or more blood spreads on slides. Stain and examine in the usual way. Reference: Bass, C. C., and Johns, F. W.: Am. Jour. Trop. Dis. and Prev. Med., No- vember, 1915, iii, 298. CHAPTER XVI MISCELLANEOUS METHODS AND TESTS FOR CARDIOLOGICAL STUDIES Exercise Tolerance Tests In the absence of all of the more exact signs upon which the capacity of the heart muscle can be estimated, the response to exer- cise may determine the management of the case and add to the diagnosis. The capacity for physical endurance is an objective criterion of the functional efficiency of the circulation and sup- plements the subjective story of the patient concerning his limita- tions on exertion. A system of graduated tests is therefore indis- pensable in any complete cardiovascular study. To this end the suggestions of Professor George Dock, Sir Thomas Lewis, Dr. Frank N. Wilson, Dr. Morris Kahn, Dr. W. D. Stroud, and others have been utilized. Methods.-The pulse rate, or the heart rate if there is an irregu- larity, is counted for a full minute and recorded while the patient is at rest in bed or sitting at ease in a chair. The respiratory rate is likewise counted and noted. The systolic and diastolic blood pressures are taken and recorded. After each of the tests that follow, records should be kept of the rise in the pulse rate; the time necessary for the return to the nor- mal level; the presence of any such symptoms as breathlessness, exhaustion and precordial or radiating cardiac pain; and the level of the blood pressure, at short intervals following the test. The heart should also be auscultated for the appearance of murmurs and the location of the apex noted with regard to evidence of enlargement. 1. Test the patient's ability to hold his breath. Note the length of the apneic periods in seconds and the pulse rate during the test. The normal length of forced apnea is from 30 to 60 seconds and there is an accompanying moderate slowing of the heart rate. In cardiac failure or effort syndrome eases, the apneic period is 189 190 METHODS IN MEDICINE rarely greater than 10 seconds. This is gross test of the vital capacity and should be verified by readings with a spirometer. 2. With hands interlocked above the head, have the patient pull for two minutes. Note the pulse rate, and if there is any rise, the length of time it takes to drop to normal, and also note any ac- companying symptoms. 3'. With the patient lying flat in bed, have him draw himself up into the sitting position five to ten times, by the use of the abdom- inal muscles only. Make blood pressure readings every minute for ten minutes and then at 2.5 and 5 minute intervals. 4. If patient is up and about make observations after a brisk walk on the level of 100 feet and 200 feet. 5. Record the phenomena after having the patient briskly walk up a flight of 40 steps. Normally this work will cause the pulse to increase 20 to 30 beats with a prompt fall to the resting rate within one minute. In mild cases of the effort syndrome, the pulse rate rises to 120-130 while in severe cases the rate reaches 150-160 per minute. The fall to normal also exceeds two minutes in duration. The blood pressure in normal individuals does not rise more than eight millimeters of mercury after this exertion while in cardiac cases it rises ten or more and in effort syndrome cases still con- siderably more. The rise may be delayed and the return to normal likewise delayed, in cases with myocardial insufficiency. 6. Note the results of running down and up a flight of 40 stairs. 7. Twenty hops on each foot, raising the shoulder six inches each time, normally causes a rise of 15 to 20 beats in the pulse rate, with a drop to normal in two minutes. Breathlessness is infre- quently exhibited by normal individuals after this test. 8. Observe the effects of having the patient bend forward, at- tempting to touch the floor with his finger tips and coming back to the erect position with the arms extended above the head, ten times. 9. Squatting by bending the knees and coming back to the erect position fifteen times will cause a rise of 25 to 30 beats in the pulse rate with a drop back in two minutes to within five of the resting rate normally. Two-thirds of normal subjects are slightly short of breath after performing this test moderately rapidly. 10. Stepping up on a chair twenty times, that is, placing one foot squarely upon a chair seat, 18 inches from the floor, and rais- MISCELLANEOUS METHODS AND TESTS 191 ing the body to the full erect position, increases the pulse rate 25 to 40 beats with a drop to normal in two minutes. Practically all average normal individuals show slight breathlessness after this amount of effort. 11. Twenty lifts of two 15 pound dumb-bells from the floor to the full length of the arms above the head, at a rate of one lift in two seconds causes a rise of 40 to 50 beats with a drop to within 10 of the resting rate in normal individuals. At the same time a fourth of the average normal individuals show considerable breath- lessness, while all show slight shortness of breath. 12. Lifting 20 pounds dumb-bells through six feet, thirty times in sixty seconds raises the blood pressure 20 mm. Hg in the nor- mal adult. In the effort syndrome case the rise averages 50 mm. Hg. Very often the effort syndrome case is unable to lift the 20 pound weights more than ten times. Raising the 20 pound dumb-bells sixty times in one hundred and twenty seconds increases the normal individual's pulse rate to 150-160, with a return to normal in a minute. The effort syndrome case, after lifting to his limit of ten times instead of sixty, pre- sents a pulse rate of 150-160 which persists for some time and does not drop to normal within two minutes. Direction for Applying the Electrodes for Taking Electrocardiograms Make up a strong salt solution by putting about a double hand- ful of salt into one quart of hot water. Soak soft hand towels in this solution. Rub patient's arms and left leg until there is a warm glow. Wrap the soft towels snugly and smoothly about the forearms and the left leg applying them moist and hot. Apply the German silver electrodes over one thickness of the soft towel as snugly as possible and then wind a bandage about the limb and the electrode. Fasten the electrodes securely in posi- tion with tape, or by several more turns of the bandage. The copper wire electrodes consist of about an arm's length of 18 gauge copper wire, which is wound about the extremity over the salt solution bandage and attached to the lead wires with double binding posts. These are best for simplicity, cheapness and efficiency. Fasten the wires to the electrodes by screwing contact screws 192 METHODS IN MEDICINE down firmly on the ends of the wires protruding beyond the insula- tion, taking care not to include the insulation. Fasten the red streaked wire to the right arm electrode the yel- low streaked wire to the left arm electrode and the green streaked wire to the left leg electrode. Unwind from the reel only the amount of wire needed to reach the wall plug and plug wires into the left hand socket of the pair. Notify the heart station that the patient is in circuit. See that the patient remains quiet and does not move arms or legs especially during the examination. The lead electrodes devised by Cohn are of advantage in getting better molding contact and consequently lower skin resistance. However, Einthoven's galvanized iron wire or, better still, copper wire electrodes as used in the heart station of the University of Michigan Hospital under the direction of Dr. Frank N. Wilson, are most satisfactory. Digitalis Standardization Cat Method Method.-Determination of the minimal fatal dose per kg. of cat, when the drug is injected slowly into the femoral vein, the stand- ard chosen being the cat unit. The cat unit is the amount of crystalline ouabain (strophanthin) which is fatal within about 90 minutes, to a kilogram of cat when the drug is injected slowly and almost continuously into the femoral vein. A cat unit is equal to almost precisely 0.1 mg. of crystalline ouabain (using 1:10,000 solution) then 10 c.c. = 0.1 mg. or one ten millionth of the weight of the animal. In testing crystalline ouabain, amorphous strophanthin or a prep- aration of strophanthus, it is only necessary to inject the solution from a syringe or burette into the femoral vein until the animal begins to show toxic symptoms. The injection is then interrupted or continued more slowly until the unmistakable signs of fatal toxicity approach. The signs are typical and characteristic. They are: MISCELLANEOUS METHODS AND TESTS 193 1. Irregularity of the heart. 2. Difficult respiration. 3. Convulsions. 4. Peculiar cry. 5. Vomiting. If death does not occur in a few minutes, the injection is con- tinued with extreme caution. In testing other members of the digitalis group in the same way, the results will be somewhat too high, 20 per cent correction being necessary. The assay may be made more accurate if 75 per cent of the total amount of the digitalis preparation is injected in the first fifteen minutes and the remainder in the following hour. Still the results are too high. The Most Accurate Method.-Inject a measured amount of the digitalis body (tincture, infusion, or digitoxin) in the first period of about ten (10) minutes. After an interval of twenty (20) minutes continue the injection substituting a solution of crystalline ouabain for that of the digi- talis body under examination until the death of the animal, or until the toxic symptoms appear. The difference between the amount of crystalline ouabain ac- tually used to complete the assay and 100 mg. per kg. of animal (amount of which would have been required in the absence of the digitalis body), represents the activity of the digitalis used. For example: A tincture representing 70 mgs. of digitalis per kg. of cat is injected into the femoral vein and after twenty to thirty minutes the injection of solution of ouabain begun. The animal may die with the typical symptoms of digitalis poisoning when 0.0142 gm. of the crystalline ouabain per kg. has been injected. The difference between the 0.0142 gm. and 0.1 gm. (which would have been required had the ouabain been used alone) is 0.0858 gm. or 85.8 per cent of a cat unit. Hence 70 mg. of digitalis equals 85.8 per cent of a cat unit and 81.6 mg. of the digitalis equals one cat unit. Dupli- cate experiments have given such close figures as 81.6 and 81.8 mg. of digitalis as one cat unit. A protocol, to demonstrate the procedure. Burette No. 1. Tinct. Digitalis (Dilution 1:10). So that, about 10 c.c. = 100 mg. digitalis or about 1 cat unit. Inject into a 2 kg. cat 10 c.c., about 50 per cent of the estimated dose. 194 METHODS IN MEDICINE Wait 30 minutes, then inject the standard ouabain. The Ouabain Solution (Stock). Ouabain (Crystalline) 35 mg. 70 per cent alcohol 35 c.c. %o,ooo- 1 c.c. = 100 mg. ouabain. Burette No. 2. Ouabain Solution (Dilution of stock solution 1:10) 1:100,000 10 c.c. = 100 mg. or one cat unit. Inject 5 c.c. of this solution. Wait ten minutes, then inject 3 c.c., wait ten minutes again, then slowly inject 1 c.c. every ten minutes until death. Death may result, for instance, just as the first 1 c.c. is given. Then the total amount of ouabain required would be 8 c.c. The estimated dose of ouabain 1:100,000 for a 2 kg. cat is 20 c.c. Therefore, the difference 20 - 8 or 12 c.c. or ouabain would have been made up by 10 c.c. of digitalis tincture 1:10. 12 :10 :: X :1, X = 1.2 Cat Units, or 1 c.c. digitalis = 120 mg. ouabain. When official preparations of digitalis, such as the tincture, are diluted with water, a precipitate occurs as is indicated by a faint opalescence. Objections as these are overcome by the combined method in which ouabain is used to complete the estimation. If approximately 50 per cent of the fatal dose of digitalis is in- jected into the vein and 20 minutes are allowed to elapse and the injection then continued, using one part of crystalline ouabain in 100,000 parts of physiologic salt solution, the end reaction is almost as sharp as with ouabain alone. This interval appears to suffice for the digitalis to exert almost its full action on the heart. Cats have been found by Hatcher and Brody that tolerated 50 per cent more than that stated. No acceptable explanation could be found; in two instances the cats were lactating. The only cats found to succumb to doses below the standard, are the excessively fat ones. Therefore, a somewhat large number of observations (at least five) are necessary to completely establish a standardization of a digitalis preparation. Reference: Hatcher, R. A., and Brody, J. G.: Am. Jour. Pharmacy, August, 1910, p. 360. MISCELLANEOUS METHODS AND TESTS 195 FOR ENDOCRINOLOGICAL STUDIES The Blood Sugar Tolerance Test The patient fasts from 7 p.m. one day until the test is completed the following morning. Omit breakfast on day of test. Ascertain the patient's weight. Before giving the glucose solution get the fasting specimen of 5 to 10 e.c. of blood, in the test tube containing a few crystals of potassium oxalate. (Test tubes containing oxalate are always to be found in the Metabolism Laboratory.) Also collect a specimen of urine, while the patient is still fasting. After the sugar is given, get the blood and urine specimens at the end of exactly one, two, and three hours. If glucose is found in any specimen, the amount and percentage is estimated and a 24-hour urine specimen is collected and the glucose estimated quantitatively. The glucose is to be given in 40 per cent solution with lemon juice, using 0.8 gm. (or 0.75 gm.) glucose per pound of body weight (1.75 gm. (or 1.5 gm.) per kg.) and each gram of glucose is dis- solved in 2.5 c.c. of water. The accompanying table (based on 0.8 gm. per pound or 1.75 gm. per kg.) gives the proper proportions of sugar, lemon juice and water for making up the solution and should be closely adhered to. BODY WEIGHT LBS. GLUCOSE GMS. LEMON JUICE C.C. WATER C.C. 90 72 54 126 100 80 60 140 110 88 66 154 120 96 72 168 130 104 78 182 140 112 84 196 150 120 90 210 160 128 96 224 170 136 102 238 180 144 108 252 190 152 114 266 200 160 120 280 210 168 126 294 220 176 132 308 230 184 138 322 240 192 144 336 Blood sugar tolerance tests should always be started early in the morning. Clinical Pathology slips are to be made out com- pletely with the Name (in full), Ward, Diagnosis, etc. (in detail). 196 METHODS IN MEDICINE Take each blood specimen to the Metabolism Laboratory as soon as withdrawn and give to the technician; and submit all urine specimens and the complete gastric contents, withdrawn through a Rehfuss tube just after the last blood specimen is taken, with the last blood specimen. The last specimen must be brought to the laboratory by noon and placed on the technician's desk. In case the technician is absent, the specimen should be put in the ice box, properly labeled, and the attention of the Interne or the Assistant Resident in Metabolism called to its presence. If specimens are not obtained exactly at the time speci- fied, note the time on the requisition so that the results can be charted accurately. Follow the standard chart exactly in recording results. The technic of Hamman and Hirschman has the advantage of using less glucose and gives reliable curves, with the water and glucose standardized to the unit weight of the individual. These investigators advise the use of 1.5 gm. glucose per kilogram of the patient's body weight (0.75 gm. per pound) and for each gram of glucose 3' c.c. of water. Standard charts of Normal and all types of curves, as those obtained in Diabetes Mellitus, Hyperthyroidism, Hypothyroidism, Renal Diabetes, Pituitary Hyperfunction and Hypofunction are to be found in the composite history, Part V. References: Hamman, L., and Hirschmann, I. I.: Arch. Int. Med., November, 1917, xx, 761. Janney, N. W., and Isaacson, V. I.: Jour. Am. Med. Assn., April 20, 1918, Ixx, 1131. Fitz, R., and others: Jour. Metabolic Research, April, 1922, i, 549. The Pharmacologic Tests The Technic of the Procedures Preparation of Patient.-The patient is put to bed on the day preceding the test and reassured as much as possible. The pres- ence or absence of nervousness, throbbing, tachycardia, tremor, depressions, "dying" spells, apprehensions, hot and cold flashes, cold hands and feet, fainting spells, etc., is recorded in detail. See Vegetative Nervous System outline of details to be observed. Notice objective signs as eye signs, tremor, thrills of thyroid, throbbing carotids. Take two readings at 5 minute intervals of the blood pressure, pulse rate, and respiration. MISCELLANEOUS METHODS AND TESTS 197 Adrenalin Test.-Give 1.75 (or 1.5) gm. glucose per kilo three hours before the test begins. It is thus advisable to do a sugar tolerance test in the morning and the adrenalin test in the after- noon of the same day. Save the 24-hour specimen and quantitate the glucose output. Before giving the injection of adrenalin, the pulse, respiration, and blood pressures are to be recorded every two to five minutes until a constant level is reached, usually after 3 or 4 readings. The patient must be at rest, flat in bed, for an hour previous to beginning the test. Inject intramuscularly, preferably into the deltoid muscle 0.5 c.c. of a 1-1000 solution of adrenalin, freshly prepared from Parke, Davis & Co.'s Adrenalin Tablets, %00 gr- or -001 gm. Per 1 c-c- Record the pulse, respiration and blood pressure every two min- utes for 10 minutes, then every 5 minutes for one hour and every 10 minutes for another half hour. The subjective symptoms are to be noted before and after the in- jection. These are nervousness and palpitation, vertigo, restlessness or any other complaints that the patient may have. Note also the objective symptoms: Flushing, sweating, increased vascular pulsa- tion, increased tremor of the hands, etc. Collect urine before the injection and one-half, one, and one and one-half hours following injection. Test each specimen for sugar; if present note the percentage and total amount in each specimen, and collect a 24-hour specimen for quantitative estimations. Pilocarpin Test.-Seven and one-half mg. to 10 mg. (%0 gr. to % gr.) of pilocarpin hydrochloride are injected usually subcutane- ously, rarely intramuscularly, and observations made with especial reference to those symptoms and signs that are described as evi- dences of a positive pilocarpin reaction. Observations are recorded at definite intervals, as described for the adrenalin test. Atropin Test.-Three-fourths to 1.0 mg. (5ioo Sr- to %0 gr.) of atropin sulphate is injected subcutaneously or intramuscularly, and the signs and symptoms looked for that are described as being present in a positive adrenalin reaction. Observations are recorded at the intervals indicated in the adrenalin test routine. 198 METHODS IN MEDICINE Pharmacodynamic Reactions The Adrenalin Reaction is positive if there is acceleration of the pulse, 30 beats or more, and the B.P. rises 10 mm. of mercury or more, with the patient also developing a high grade tremor of the hands, and a glycosuria, totaling 3 gm. in 24 hours on an intake of 1.75 gm. or 1.5 gm. per kilo of body weight, or a single dose of 100 gm. of glucose, ingested three hours before the test is begun. The respiration rate, and occasionally the temperature, rises; der- mographia, facial pallor, and the ocidocardiac reflex become more prominent. The eosinophiles decrease markedly and practically disappear. All these signs and any other objective phenomena are recorded, as are also the patient's subjective symptoms. Goetsch insists that a positive reaction consists not only in an early rise in B.P. and pulse over 10 points at least in each, but also in a moderate fall and a slight secondary rise at thirty to thirty-five minutes after injection; then a second fall to normal in about one and one-half hours. A positive reaction indicates increased irritability of the sympa- thetic nervous system. The Pilocarpin Reaction is positive if heavy lachrimation and salivation appear, or if with slight perspiration the amount of saliva secreted totals 75 c.c. Besides this the eosinophiles increase relatively and absolutely. Further there is an increase in dermo- graphia and the oculocardiac reflex. The B.P. usually falls 10 to 20 points. The temperature and any other objective changes are recorded along with all subjective symptoms. Quite frequently there are epigastric pains, vomiting, tenesmus, diarrhea, headache, vertigo and hot flushes; even typical asthmatic attacks have been described. A positive reaction denotes abnormal vagus irritability. The Atropin Reaction is positive if there is a rise in the pulse rate of 20 or more, and the developing of severe dryness of the mouth, together with palpitation of the heart, dilatation of the pupil, and dermographism. Any other objective and all subjec- tive symptoms are recorded. A positive reaction denotes susceptibility to vagus paralysis as MISCELLANEOUS METHODS AND TESTS 199 one finds in vagotonic individuals in whom the heightened vagus irritability rapidly goes over into paralysis. References: Barker and Sladen: Tr. Assn. Am. Physic., 1912, xxvii, 471. Neumann: Die Therapie der Gegenwart., 1919, xxi, 241. Goetsch, E.: New York State Med. Jour., July, 1918, xviii, 259. Peabody, F. W., Sturgis, C. C., and Tompkins, E. H.: (A) Arch. Int. Med., September, 1919, xxiv, 247-269. (B) Am. Jour. Med. Sc., Oct., 1919, clviii, 406. (C) Jour. Am. Med. Assn., December, 1918, Ixxi, 1912. Details to Observe when Taking the Status of the Vegetative Nervous System General Condition: Nutrition Habitus. Lymphatic constitution: Goiter Individual peculiarities. Skin: Dry or moist Dermographism Rapid changes of color Pigmentation Type of hair growth. Eye Symptoms: Eyes brilliant (Wide fissure) Lacrimation Exophthalmos Strabismus Spasm of accommodation Loewe's test (Dilatation of pupil on instilling 3 drops 1/1000 adrenalin into conjunc- tivae) Duration of atropin mydriasis Other symptoms. Secretions: Sweating Salivation Lacrimation Other symptoms. Heart: Bradycardia Tachycardia Extrasystoles Respiratory irregularities Tschermak's (Slowing of pulse by pressure on the vagus opposite the carotid) Aschner's (Slowing of the pulse by pressure on the eye ball) Angina Pectoris. Lungs: Frequent respiration Asthma Laryngeal crises Other signs. Stomach: Pain Eructation Test meal or functional test Spasm in fluoroscopic examination Type Other symptoms. Intestines: Spastic constipation Nervous diarrhea Mucous colitis Eosinophilous catarrh. Urine: Polyuria Alimentary glycosuria Brick dust sediment Oxyluria Phosphaturia Other symptoms. Central Nervous System: Tendon reflexes Abdominal reflexes Pharyngeal reflexes Chvostek's tremor Tremor Other symptoms. Mental Condition: Irritability Other symptoms or signs. Blood: Anemia Chlorosis Eosinophilia Other findings. 200 METHODS IN MEDICINE Symptoms of Increased Vagotony and Sympatiiicotony ORGAN SIGNS OF INCREASED VAGOTONY SIGNS OF INCREASED SYMPATHICOTONY VEGETATIVE NEUROSES (ALMOST ALL VAGUS NEUROSES) General Status Asthenic habitus Lymphatic constitu- tion Eye Narrow pupils Spasm of accommoda- tion Wide fissure Convergent strabismus Lacrimation Fleeting atropin my- driasis Glands Salivation Perspiration Skin Pigmentation Dermographia Moist hands and feet Dry skin Loss of hair Goose flesh Heart and Ves- sels Many forms of Bradycardia Respiratory irregular ity of pulse Aschner's sign (Brad ycardia on pressing eye ball) Tschermak's sign (Vagus pressure fol- lowed by bradycar- dia and sometimes vomiting, ver t i g o and collapse.) Erben's sign. (Brady- cardia on flexing trunk) Lowered blood pres- sure Many kinds of Tachy- cardia Increased blood pres- sure Many kinds of Heart block Angina pectoris vasomotoria Vagotonic cardiac neurosis with brady- cardia Sympathicotonic cardiac neur o s i s with tachycardia Lungs Irregular Respiration Bronchial asthma Laryngeal crises Stomach Hyperacidity Hypersecretion Hypermotility Increased tonus Inhibition of gastric motility Gastric hyperacidity Gastric ulcer Cardiopyloric Spasm Esophagial spasm Hour-glass stomach Intestines Hyperperistalsis Spastic condition Increased secretion Inhibition of Intes- tinal function Nervous diarrhea Colica mucosa Eosin ophilous ca- tarrh, spastic con- stipation Blood Eosinophilia Lymphocytosis Hypoeosinophilia Neutrophilia Hyperleucocytosis MISCELLANEOUS METHODS AND TESTS 201 Symptoms of Increased Vagotony and Sympathicotony--Cont'd. ORGAN SIGNS OF INCREASED VAGOTONY SIGNS OF INCREASED SYMPATHICOTONY VEGETATIVE NEUROSES (ALMOST ALL VAGUS NEUROSES) Nervous System Increased reflexes Weak pharyngeal re flexes General excitability Genital Ejaculatio precox Emissions Urine Pollakiuria Dribbling Oxaluria Phosphaturia Brick dust sediment Postural albuminuria Metabolism Increased Glucose Alimentary glycosuria Many cases of urti caria Pharmacologic Reactions: Pilocarpin Hydrochloride 0.01 gm. Increased perspiration Increased saliva Nausea Vomiting Diarrhea Atropin Sulphate 0.001 gm. Increase of pulse 30 or more Dry mouth Adrenalin 0.001 gm. Increase of pulse 30 or more points Increased blood pres- sure Tremor Palpitation Increased respiration Alimentary glycosuria Rise of temperature The Thyroid Test Based upon the idea that cases of mild hyperthyroidism are sensitive to thyroid extract while cases of pure neurotic consti- tution are not, a test has been put forth, and strongly advocated by some, as a distinct aid in the differential diagnosis. Definite and graduated increase in doses of thyroid extract are administered by mouth and the pulse rate counted regularly and any general reactions as increased tremor, nervousness, perspiration, flushing, eye signs or changes in the gland noted. Four doses each of a half, one and two grains of freshly pre- 202 METHODS IN MEDICINE pared thyroid extract in tablets given on successive days consti- tute the test. The pulse rate is recorded at four hourly intervals for 24 hours. Then the following day the half grain tablets are taken with a swallow of water at two hourly intervals for four doses, namely at 8, 10, 12, and 2 o'clock and the pulse recorded every two hours, namely at 9, 11, 1, 3, 5 and 7 o'clock. The second day the four one grain tablets are taken at the same even hours and the pulse recorded at the alternate odd hours with conditions as nearly identical as possible. During the third day the four two grain tablets are likewise taken and similar observations are made. For two more days observations are made at the stated times. If at any time during the test symptoms or signs of thyroid over- activity appear, the administration of the extract must be dis- continued. References: narrower, H. R.: Med. Rec., 1919, xcvi, 722. Escudero, P.: Riv. de la Assoc, med. Argentina, 1920, xxxiii, 321. The fact that the content of the active principle thyroxin in desiccated thyroid gland or even in the fresh gland is not uniform or constant and cannot be accurately standardized, makes the use of this preparation in a quantitative physiologic test open to criticism. Furthermore many patients show a distinct failure of absorption of the active principle of the preparation from the intestinal tract or its destruction in the process of digestion so that isolated cases have been given 20 grains in one dose or 250 grains daily without any reaction (Plummer). This nonabsorption together with the facts that the desiccated gland cannot be given intravenously, that the thyroid gland is probably placed at rest by the routine administration, and that the thyroid under certain con- ditions stores thyroxin, makes it impossible to draw conclusions from an attempted quantitative study of the reactions of persons having functioning thyroid glands. Thyroxin Thyroxin tablets might be substituted for the thyroid extract and thus the objection to the variable nonstandard extract, of uncer- tain active principle content, might be met. However, daily doses of 2 to 3 mg. of thyroxin given by mouth will not affect the basal metabolism or cause any physiologic reaction in many individuals MISCELLANEOUS METHODS AND TESTS 203 in whom the same close given intravenously causes a standard, quan- titative reaction. Thyroxin in crystals in vials of 10 to 100 milligrams is supplied by E. R. Squibb & Sons. For using intravenously thyroxin crystals in weighed amounts, 1 or 2 milligrams are placed in a small sterile test tube. One drop of 10 per cent sodium hydroxide solution and 1 c.c. of water are added. The solution is warmed and agitated until the crystals are dissolved, and the solution is then sterilized by placing the tube in boiling water. The solution is taken up in a sterile hypodermic syringe, the test tube is rinsed with 1 c.c. of sterile distilled water, which is also drawn into the syringe con- taining the thyroxin solution. The syringe content is then in- jected intravenously. The amount of thyroxin that may be tolerated by any patient may be estimated after determining the basal metabolic rate. In an adult weighing about one hundred and fifty pounds, one milli- gram of thyroxin given intravenously increases the basal metabolic rate 2 per cent. In the thyroidless individual, the basal metabolism is from 30 to 40 per cent below the average normal. A single dose calculated to bring the basal metabolism to normal may be administered intra- venously and in from ten to twelve days the physiologic status becomes normal and remains practically so for ten days, and then drops gradually to the low level again in from five to eight weeks. The average normal man holds approximately 14 mg. (Kendall) of thyroxin in the tissues of the body other than that in the gland itself. The average daily exhaustion of thyroxin in the body is between a half and one milligram. Thyroxin, 1.6 mg., per os will hold the thyroidless individual within the normal limits of the basal metabolism. Two to 3 mg. of thyroxin per os in many nor- mal individuals has no effect. Intravenously 2 mg. of thyroxin per day may hold the basal metab- olism from 20 to 30 per cent above normal, while 3 mg. per day may hold the metabolism 50 per cent above normal. Thus every intravenous dose of more than 1 mg. of thyroxin has been followed by a sustained elevation of the basal metabolism except for two types of cases, viz., exophthalmic goiter with a basal metabolism above +65 who may show no notable reaction from as much as 15 mg. doses given intravenously, and likewise patients with large 204 METHODS IN MEDICINE colloid goiter with bruit, after similar dosage show no constitu- tional reaction, although the thyroid often shrinks rapidly and the bruit disappears. Reference: Plummer, H. S.: Jour. Am. Med. Assn., July 23, 1921, Ixxvii, 243. Pituitrin Test Extract of the posterior lobe of the hypophysis, in which one c.c. in normal saline is equivalent to a half of the posterior lobe of the hypophysis of a beef or the equivalent of 5 centigrams of powdered posterior lobe obtained from desiccating 10 centigrams of fresh pos- terior lobe is used. One c.c. of a standardized extract (surgical) of posterior lobe of the pituitary body may be substituted and injected subcutaneously. In normal individuals there is an excitation of the sympathetic nervous system, vasoconstriction of the skin vessels and conse- quently pallor. Glycosuria also presents with moderate sugar in- take. Excessive intestinal peristalsis is often present. The pulse is increased in rate from 5 to 30, the maximum being reached in 5 or 6 minutes with a return to normal within 15 minutes and a slight fall in blood pressure. In neurotic individuals with tachy- cardia, or a case with any type of tachycardia other than that pro- duced by hyperthyroidism, there is no slowing of the pulse rate and only a very slight if any drop in the blood pressure. In hyperthyroidism or exophthalmic goiter there is a distinct slowing of the pulse within two minutes and lowering of the blood pressure. The effects last for only 6 to 8 minutes. In hyperthyroidism, cretinism, or myxedema there is an accel- eration of the pulse and a slight to moderate drop in the blood pressure. Acromegalic cases show no reaction whatsoever to pituitrin even in large doses. Diabetes insipidus cases often show a distinct control of the diuresis following the injection of pituitrin. References: Claude, H., Baudouin, A, and Porak, R.: Soc. Med. des Hop., June, 1914, xxxvii, 1094. Claude H., and Bernard S.: Soc. Med. des Hop., Dec., 1919, xliii, 1116. Nelson, E. E.: Jour. Lab. and Clin. Med., Feb., 1923, viii, 318, Jour. Am. Med. Assn., Ixxx, 1423. MISCELLANEOUS METHODS AND TESTS 205 FOR IMMUNOLOGICAL STUDIES The Tuberculin Test Afebrile cases alone should be subjected to the test. The patient is to be kept in bed for at least 24 hours and preferably 48 hours before the test is made. During this preliminary observation pe- riod, the rectal .temperature is recorded every two hours and the pulse and respirations noted. The chest is carefully auscultated at 12-hour intervals and any local lesions elsewhere examined and notes kept of the findings. Dilutions of Koch's old tuberculin (O.T.) with normal saline solution (NaCl .9 per cent) are then made with a tuberculin syringe graduated in 0.001 c.c. A. .1 c.c. O.T. + 9.9 c.c. NaCl .9 per cent -1:100 .1 c.c. = 1 mg. 1 c.c. = 10 mg. B. .1 c.c. A + .9 c.c. NaCl .9 per cent = 1:1000 .1 c.c. = 1 mg. 1 c.c. = 1 mg. The intradermal test dose is .1 to .5 mg. with a saline control injection. The first subcutaneous test dose should equal 1 mg. of tuberculin and if this is accompanied by no reaction, successive doses of 5 mg. and 10 mg. should be given at three-day intervals. The injection of the tuberculin should be made at 8 o'clock p.m. as typical re- actions manifest themselves between 12 and 24 hours following the injections. The patient should be kept quiet, and the rectal tem- perature observations continued every two hours with accompany- ing pulse and respiration observations at these intervals. The site of the injection is watched for local reaction. The lungs should be carefully auscultated 12 hours after the in- jection and every two hours thereafter during the day and evening. At these intervals any local lesions suspected of being tuberculous and the site of the injection should be examined for inflammatory changes. The patient's general symptoms should also be noted. The positive reaction is one in which vague and questionable symp- toms and physical signs are made definite. There must be a local reac- tion, a rise in temperature of over one degree and nearly two degrees, accompanied by a certain degree of malaise and discomfort, and changes in the physical signs in the chest even to the development of rales or an inflammatory reaction in a local lesion suspected of being tuberculous. 206 METHODS IN MEDICINE The Schick Test Standard strength diphtheria toxin can be obtained from the Research Laboratory of the New York City Department of Health and some commercial laboratories. The outfit from the above lab- oratory consists of a small glass capillary tube containing a meas- ured amount of the undiluted toxin, a small rubber.bulb for expell- ing the toxin, and a 10 c.c. vial of sterile saline for making enough of the dilution for about 35 tests is thus obtained. Undiluted, the toxin is good for six months in the cold, while after dilution it is good for twenty-four hours only. The dose is of a M.L.D. in 0.1 or preferably 0.2 c.c. of saline. The test fluid is taken up in a 1.0 c.c. sterile Record syringe with a sterile 26 gauge % inch steel needle attached. Any alcohol present must be rinsed away with the test fluid. The technic is important; the injection must be made intradermally and not subcutaneously. Two-tenths c.c. of the unheated accurately diluted toxin is intra- dermally injected in the skin of the flexor surface of the right forearm 5 cm. from the bend of the elbow, and a similar amount of the heated diluted toxin is similarly injected in the left forearm, as a control. A small blanched out wheal-like swelling in the skin results from the injection. In a susceptible person, there will appear a positive reaction at the site of injection within 24 to 36 hours, a definite well circumscribed area of redness about 1 to 2 cm. across, which gradually increases within the next forty-eight or seventy-two hours, reaching its height in ninety-six hours at which time final definite readings are made. The reaction persists for a week or more, depending upon the intensity of the reaction, leaving a fad- ing, at first definitely scaling, pigmented area, which gradually disappears. The control remains negative. In an immune person, a negative reaction shows no change in the skin at the site of the injection. The pseudonegative reaction must be carefully differentiated from the positive reaction. It is anaphylactic in nature and due to autolyzed diphtheria bacillus protein. The control test on the left forearm with toxin heated to 75° C. for ten minutes distin- guishes the pseudonegative reaction. Pseudoreactions usually have faded completely by the fourth day when the positive reaction is MISCELLANEOUS METHODS AND TESTS 207 at its height. In adults, there occur two to three times as many pseudonegative reactions as positive reactions. References: Zingher, A.: Jour. Lab. and Olin. Med., December, 1920, vi, 117. Schick, B.: Munchen. med. Wchnschr., 1913, lx, 2608. Intracutaneous Pneumotoxin Test The technic of preparation and the properties of pneumotoxin: Briefly stated, the hemolytic endotoxin of the pneumococcus is produced as follows: from 1,000 to 1,500 c.c. of an eighteen hour broth culture of virulent type 1 pneumococci (Rockefeller Insti- tute) are centrifugalized for one hour in a powerful electric cen- trifuge at very high speed. The bacterial sediment is washed once in isotonic salt solution, taken up in 5 c.c. of saline and dis- solved in 1 c.c. of a 2 per cent solution of sodium choleate. The total volume is made up to 30 or 40 c.c.; the solution is again centrifugalized, to remove any undissolved pneumococci, and tri- cresol is added up to 0.25 per cent concentration. The "control fluid," containing no toxin, is made similarly. The preparations are preserved in the refrigerator and they are never used when older than eighteen to twenty-four hours, since the toxin deterio- rates very rapidly. All preparations are perfectly homogeneous and slightly opalescent. Note: The method of standardization has been described by the authors. In routine studies it is found impracticable to determine both the minimum lethal dose and minimum hemolytic dose of each lot of pneumotoxin, and only three out of the five employed are tested. The minimum lethal dose (tested after the total volume has been made up to 100 c.c.) is about 6 or 7 c.c. for a guinea pig weigh- ing from 2'50 to 300 grams, and the minimum hemolytic dose is from 0.2 to .04 c.c. when titrated in terms of a 1 per cent suspension of washed guinea pig erythrocytes. The dose of toxin used in skin tests (0.1 c.c.) represents therefore about one-twentieth the min- imum lethal dose. The results of the tests done on children are of particular inter- est because these patients are less prone to be sensitized to various foreign proteins and above all the disease generally runs a more definite course, not being complicated by alcoholism, tuberculosis, etc. The appearance of the skin reaction to pneumotoxin is in all 208 METHODS IN MEDICINE respects similar to that described for the Schick test with diph- theria toxin. Reference: Weiss, C. and Kolmer, J. A.: Jour. Immunol., 1918, iii, 395. Arch. Int. Med., 1923, xxxi, 262. Protein Sensitization Tests The cutaneous test by which hypersensitivity can be determined may be carried out either by a linear cut or the introduction of the protein solution intradermally. After cleansing the flexor surface of the forearm, linear cuts about .5 cm. in length and 4 cm. apart are made without drawing blood. Blood in minute quantities does not interfere with the test, but is considered poor technic and unnecessary. One control is located near the bend of the .elbow, the second control near the wrist. The powdered protein is placed on the cuts between the controls. N/10 (.4 per cent) sodium hydroxide is used as the diluent, the diluent alone being placed on the control cuts. During the- test the protein must be kept in the solution, drying being pre- vented by the addition of further diluent. After the dissolved protein has remained in contact with the cuts for one-half hour, it is wiped away and the reading made; the reaction always being compared with the controls. If a reaction appears in a few minutes, and rapidly becomes larger, accompanied by intense erythema and itching, it is well to wipe away the protein, thus preventing further absorption and the pos- sibility of the disagreeable symptoms of acute anaphylaxis. Sensitivity to pollen can be determined by using the dry pollen and N/10 sodium hydroxide as the diluent; however, pollen protein is usually supplied in solution, the diluent being 14 per cent alcohol in normal saline. When testing, therefore, for pollen sensitivity with commercial solutions, 14 per cent alcohol in normal saline should be used as the control. The intradermal test is performed by means of a hypodermic syringe, using a fine needle (26 gauge), the needle being intro- duced in the most superficial layers of the skin. A good guide for the proper technic of the method, is to be able to see the eyelet of the needle through the skin. Enough protein solution is in- jected to form a small papule 2 mm. to 5 mm. in diameter. The reading should be made in 15 to 30 minutes, comparing the reaction produced by protein solution, with the control, which is normal saline solution introduced into the skin in a similar manner. CHAPTER XVII PHYSIOLOGIC CHEMISTRY METHODS Metabolism Laboratory of the Department of Internal Medicine Determination of Gaseous Regulation of Respiratory Air Collection.-Haldane's method of collection of alveolar air. The subject takes the apparatus (with large stopcocks open and small stopcocks closed) into his mouth, places his tongue against the end of the tube and breathes normally. At the end of a normal ex- piration he closes his lips on the tube, removes his tongue from the end of the tube and empties his supplemental air completely into the tube, seals it at once with his tongue and closes the two large stopcocks. A sample is then removed for analysis by displacing the air with acidulated water. In the same way a second sample is drawn during an expiration made at the close of a normal in- spiration. The average composition of these two samples gives the composition of alveolar air. Haldane's method of analysis. The percentage of O2 and CO2, and from these the tensions of these gases, are then determined by the Haldane method, the details of which will be found in the reference texts. Plesch-Higgin's method of collection of alveolar air. The Plesch- Higgins bag is first emptied of air and then filled with 600 c.c. of room air with an ordinary atomizer bulb which delivers about 50 c.c. of room air into the bag at each compression. The outlet tube is then clamped. The subject, while at rest and breathing naturally, takes the tube of the apparatus in his mouth at the end of a normal expiration and begins to breathe the room air while closing his nose with the thumb and forefinger of the hand holding the apparatus. At the end of a normal expiration the ob- server turns the valve and the subject breathes in all of the air in the bag. He then breathes back and forth into and out of the bag at the rate of one complete respiration in 5 sec. The attend- ant should mark the time, indicating when breathing should be in 209 210 METHODS IN MEDICINE and out. At the end of four complete respirations, viz., 20 seconds, at the end of an expiration, the subject is again permitted to breathe the room air, while the tubing to the bag is clamped with the pinchcock. The air in the inflated bag has the same satura- tion with CO2 as the dead space in the lungs and the alveoli and is used for the analysis, within three minutes. Analysis.-Marriott's method of analysis to determine the tension of the CO2 of the alveolar air. Pour 2-3 c.c. of the standard bi- carbonate solution into the long test tube, filling the latter about one-fourth full. Place a capillary nozzle tube in the outlet tube of the bag containing the sample. Immerse the end of the capil- lary delivery tube in the standard bicarbonate solution, release the pinchcock and allow 100 c.c. of the sample of air to bubble rapidly through the solution in about 30 sec. to 1 min. or until no further color changes occur. Stopper the tube immediately and compare its color with that of the standard tubes by placing it in the center section of the comparison box and the standard solution most nearly approaching it on either side. The determination should be carried out at a temperature of from 20° to 25° C. (68°-78° F.). If the temperature of the room is above or below this, the specimen should be immersed in water at 25° C. while being saturated with the gas to be examined. The Standard Bicarbonate Solution.-This contains 0.53 gm. of desiccated sodium carbonate to 200 c.c. of a 0.01 per cent solution of phenolsulphonephthalein to 1000 c.c. Or, one may prepare 100 c.c. N/10 sodium hydroxide solution, plus 200 c.c. of a 0.01 per cent phenolsulphonephthalein solution, and dilute the mixture to 1000 c.c. The Standard Acid-alkaline Phosphate Mixture.-A N/15 acid potassium phosphate solution is prepared by dissolving 9.078 gms. of the pure, recrystallized salt in 200 c.c. of a 0.01 per cent solu- tion of phenolsulphonephthalein solution and diluting to 1000 c.c. In addition, a N/15 solution of disodium phosphate is prepared. To this end a quantity of the pure recrystallized salt of the com- position Na,HPO412H2O is exposed to the air, protected from the dust, for about two weeks. During that time the salt loses 10 molecules of water, and a product is obtained having the com- position Na2HPO42H2O. Of this 11.876 gm. are dissolved in PHYSIOLOGIC CHEMISTRY METHODS 211 200 c.c. of a 0.01 per cent solution of phenolsulphonephthalein and the volume brought to the 1000 c.c. mark. The following mixtures are prepared, corresponding to carbon dioxide tensions as indicated. 10 15 20 25 30 35 40 45 Acid phosphate solution c.c. 17.8 25.2 31.0 35.7 40.5 45.0 47.0 50.2 Alkaline phosphate solution c.c. 82.2 74.8 69.0 64.3 59.5 55.0 53.0 49.8 Specimens of the standard colored solutions are put up in small nonsoluble glass tubes (10 x 75 mm.), which are sealed. It is best to add a little thymol or toluol to prevent moulding. They are kept in the dark when not in use and by means of a small col- orimetric rack are compared with the unknown made from the patient's air. A compact outfit is made by Tlynson, Westcott and Dunning, of Baltimore. Apparatus.-Marriott's alveolar air testing outfit consists of: 1 set of eight nonsoluble glass tubes filled with standardized phosphate solutions colored with phenolsulphonephthalein and numbered 10, 15, 20, 25, 30, 35, 40, and 45 mm. re- spectively. 1 long nonsoluble glass test tube. 1 nonsoluble glass capillary nozzle. 1 metallic comparison box arranged to hold the specimen and two color tubes. 1 glass mouth piece. (All of the above contained in a wooden box.) 100 c.c. standardized sodium bicarbonate indicator solution. Accessories (Optional).- 1 Rubber bag, 500, 1000, or 1500 c.c. capacity. 1 Atomizer bulb. 1 Pinchcock. Special mask for comatose patients with three way metal stop cocks. References: Boothby, W. M., and Peabody, F. W.: Arch. Int. Med., Mar., 1914, xiv, 497. Marriott, W. McK.: Jour. Am. Med. Assn., May 20, 1916, Ivi, 1594. Test: Barcroft: The Respiratory Function of the Blood, 1914, p. 311. Haldane: Methods of Air Analysis, pp. 9-55, London, Griffin, 1912. Boothby and Sandiford: Basal Metabolic Rate Determination, Philadelphia, W. B. Saunders, 1920. 212 METHODS IN MEDICINE Plasma and Whole Blood CO., Determination Van Slyke's Modified Method To estimate the blood CO2 combining power, the blood should be taken after the patient has been at rest for at least an hour. Stasis is also to be avoided during the withdrawal of the sample of blood. Whole blood would give the most accurate estimation of the alkaline reserve, but the slight inaccuracy of the plasma method does not overrule the advantages of using it alone in routine estimations. The plasma is obtained by centrifuging the oxalated blood. Three c.c. are placed in a 300 c.c. separatory funnel and saturated with CO2 at the alveolar air tension of 5.5 per cent, by air from the lungs passed through a bottle full of glass beads. Normal inspiration should be followed by quick complete expiration through the glass beads into the funnel. The funnel is stoppered and turned end over end for two minutes to spread the plasma over the entire surface as thinly as possible, so as to get saturation. The Van Slyke apparatus has three positions in which the mer- cury leveling bulb is used, so that the lower end of the leveling bulb is on a level (1) with the upper stopcock; (2) with the lower end of the pipette itself below the lower stopcock and (3) 80 cm. below the end of the pipette itself. To begin, the whole apparatus including both capillaries above the upper stopcock is entirely filled with mercury. To test for tightness, the leveling bulb is placed 80 cm. below the end of the pipette, the mercury will drop to the middle of the extraction chamber, and on raising the leveling bulb the entire apparatus should fill completely striking the upper cock with a sharp click. 1. Rinse the cup out with water instead of the original 1 per cent ammonia solution, and then run into it 1 c.c. of distilled water. Run 1 c.c. of saturated plasma or whole blood under this layer of water. A drop of octyl alcohol is added. With the mer- cury bulb in position 2 and the lower cock in such a position that a connection is established between the pipette and the right hand chamber below the cock, the upper cock is opened and the blood or plasma followed by the layer of water washing down the walls of the cup, is run into the chamber of the apparatus. PHYSIOLOGIC CHEMISTRY METHODS 213 2. After the above fluids are run into the apparatus and only the drop of alcohol remains in the capillary above the cock, the 0.5 c.c. of N. lactic acid, 1 volume of concentrated acid (sp. gr. 1.20) diluted to 10 volumes with water instead of N. sulphuric acid is measured into the cup and run through into the chamber. The total amount of water solution must measure exactly 2.5 c.c. on the apparatus. A drop of mercury is placed in the capillary and allowed to run as far as the cock in order to seal it after the acid has been run in. The mercury bulb is lowered and hung at position 3 and the mercury in the pipette is allowed to fall to the 50 c.c. mark, thus producing a vacuum. As the mercury reaches the 50 c.c. mark exactly, the lower cock is closed, the ap- paratus unclamped and turned upside down 15 or more times to extract the CO, from the 2.5 c.c. fluid, producing an equilibrium between that in the solution and that in the partial vacuum. The water solution alone is then run from the pipette through the lower stopcock into the right-hand lower chamber. Care is to be taken that no gas follows. The mercury bulb is raised and the lower cock is turned to connect the pipette with the lower left chamber. The mercury rises in the pipette body and calibrated stem to the level of the gas extracted from the solution. The surface of the mercury in the leveling bulb is made to correspond with the surface of the mercury in the pipette, thus producing atmospheric pressure for the gas in the pipette. The volume of gas is then read on the pipette scale. To determine the CO, bound as bicarbonate by the plasma, the following equation is solved. X = (100.8 - 0.27t) (V - 0.136 + 0.002t) X = c.c. of CO2 at 0° and 760 mm. pressure, which 1 c.c. of plasma will bind as bicarbonate when in equilibrium at 20° C. with air containing 5.5 per cent by volume of CO2. B = barometric pressure, and t = temperature at which the test was made, and V = the actual reading in cubic millimeters of the gas in the pipette. Measurement of CO, without removal of the plasma solution from the measuring chamber can be accomplished without increased ab- sorption of CO2, thus obviating one step in the analysis. After extraction of the gas, the lower cock is opened, admitting the mer- 214 METHODS IN MEDICINE cury into the extraction chamber rapidly until the water level reaches the narrow calibrated portion of the tube. At this point the lower stopcock is partially closed and the remainder of the mercury let in at a slow enough rate to prevent oscillation of the water column in the calibrated portion of the apparatus when the pressure equilibrium is reached. The leveling bulb surface is placed the water column length, above the level of the mercury surface in the chamber in order to balance the latter. The level- ing scale of Stadie is the most accurate method in estimating the correct level. With the pressure adjusted, the lower stopcock is closed, the gas volume read and the calculations made. In the absorption of the CO2 in the mixture of gases obtained after extraction of whole blood, 0.5 N. NaOH is now used instead of 10 per cent KOH. The dilute alkali floats and forms a clear meniscus. In running it into the chamber, the mercury in the leveling bulb is held a few centimeters below the surface of the mercury in the chamber to produce a slight negative pressure. When the CO2 is reabsorbed by alkali solution, as in the analysis of the whole blood, as contrasted to the plasma analysis in which the acid solution contains only a negligible amount of CO2, the apparatus must be carefully and completely washed out after each analysis. To wash the apparatus, the upper cock is closed and the level- ing bulb dropped to its lowest level. The 6 c.c. cup at the top Table I Factors for Correction for Barometric Pressure BAROMETER B 760* BAROMETER B 760 732 0.963 756 0.995 734 0.966 758 0.997 736 0.968 760 1.000 738 0.971 762 1.003 740 0.974 764 1.006 742 0.976 766 1.008 744 0.979 768 1.011 746 0.981 770 1.013 748 0.984 772 1.016 750 0.987 774 1.018 752 0.989 776 1.021 754 0.992 778 1.024 PHYSIOLOGIC CHEMISTRY METHODS 215 Table II For Calculation of Carbon Dioxide Combining Power of Plasma Observed vol. gas C.c. of CO2 reduced to O° 760 mm. bound as bicar- bonate by 100 c.c. of plasma Observed vol. gas B X 760" C.c. of COo reduced to 0° 760 mm. bound as bicar- bonate by 100 c.c. of plasma 15° 20° 25° 30° 15° 20° 25° 30° 0.20 9.1 9.9 10.7 11.8 0.60 47.7 48.1 48.5 48.6 1 10.1 10.9 11.7 12.6 1 48.7 49.0 49.4 49.5 2 11.0 11.8 12.6 13.5 2 49.7 50.0 50.4 50.4 3 12.0 12.8 13.6 14.3 3 50.7 51.0 51.3 41.4 4 13.0 13.7 14.5 15.2 4 51.6 51.9 52.2 52.3 5 13.9 14.7 15.5 16.1 5 52.6 52.8 53.2 53.2 6 14.9 15.7 16.4 17.0 6 53.6 53.8 54.1 54.1 7 15.9 16.6 17.4 18.0 7 54.5 54.8 55.1 55.1 8 16.8 17.6 18.3 18.9 8 55.5 55.7 56.0 56.0 9 17.8 18.5 19.2 19.8 9 56.5 56.7 57.0 56.9 0.30 18.8 19.5 20.2 20.8 0.70 57.4 57.6 57.9 57.9 1 19.7 20.4 21.1 21.7 1 58.4 58.6 58.9 58.8 2 20.7 21.4 22.1 22.6 2 59.4 59.5 59.8 59.7 3 21.7 22.3 23.0 23.5 3 60.3 60.5 60.7 60.6 4 22.6 23.2 24.0 24.5 4 61.3 61.4 61.7 61.6 5 23.6 24.2 24.9 25.4 5 62.3 62.4 62.6 62.5 6 24.6 25.2 25.8 26.3 6 63.2 63.3 63.6 63.4 7 25.5 26.2 26.8 27.3 7 64.2 64.3 64.5 64.3 8 26.5 27.1 27.7 28.2 8 65.2' 65.3 65.5 65.3 9 27.5 28.1 28.7 29.1 9 66.1 66.2 66.4 66.2 0.40 28.4 29.0 29.6 30.0 0.80 67.1 67.2 67.3 67.1 1 29.4 30.0 30.5 31.0 1 68.1 68.1 68.3 68.0 2 30.3 30.9 31.5 31.9 9 69.0 69.1 69.2 69.0 3 31.3 31.9 32.4 32.8 Q 70.0 70.0 70.2 69.9 4 32.3 32.8 33.4 33.8 4 71.0 71.0 71.1 70.8 5 33.2 33.8 34.3 34.7 5 71.9 72.0 72.1 71.8 6 34.2 34.7 35.3 35.6 6 72.9 72.9 73.0 72.7 7 35.2 35.7 36.2 36.5 7 73.9 73.9 74.0 73.6 8 36.1 36.6 37.2 37.4 8 74.8 74.8 74.9 74.5 9 37:1 37.6 38.1 38.4 9 75.8 75.8 75.8 75.4 0.50 38.1 38.5 39.0 39.3 0.90 76.8 76.7 76.8 76.4 1 39.1 39.5 40.0 40.3 1 77.8 77.7 77.7 77.3 2 40.0 40.4 40.9 41.2 2 78.7 78.8 78.7 78.2 9 41.0 41.4 41.9 42.1 3 79.7 79.6 79.6 79.2 4 42.0 42.4 42.8 43.0 4 80.7 80.5 80.6 80.1 5 42.9 43.3 43.8 43.9 5 81.6 81.5 81.5 81.0 6 43.9 44.3 44.7 44.9 6 82.6 82.5 82.4 82.0 7 44.9 45.3 45.7 45.8 7 83.6 83.4 83.4 82.9 8 45.8 46.2 46.6 46.7 8 84.5 84.4 84.3 83.8 9 46.8 47.1 47.5 47.6 9 85.5 85.3 85.2 84.8 0.60 47.7 48.1 48.5 48.6 1.00 86.5 86.2 86.2 85.7 216 METHODS IN MEDICINE is filled with water,-while the mercury in the apparatus is falling. The apparatus is evacuated and nearly all the water from the cup is let in washing the entire chamber. The water is ejected and the rinsing repeated. One c.c. of water is left in the cup to start the next analysis. For the determination of all the gases in 1 c.c. of blood of carbon monoxide and nitrogen, of CO2 volume per cent within an error of 0.5 and O2 determination within an error of 0.25 the new finer bore Van Slyke apparatus is preferable. (Emil Greiner, New York.) While for CO2 as a measure of the alkaline reserve and O2 capacity as a measure of hemoglobin the original apparatus is adequate. The average normal for man is 52.5 to 77.5 volumes per cent of CO2. References: Van Slyke, D. D., and Cullen, G. E.: Jour. Biol. Chem., June, 1917, xxx, 289. Van Slyke, D. D.: Ibid., 347. Van Slyke, D. D., and Stadie, W. C.: Ibid., November, 1921, xlix, 1. Blood Oxygen Determination Van Slyke's Modified Method The original Van Slyke apparatus is adequate for the determi- nation of the blood oxygen capacity, as a measure of hemoglobin, but when it is essential to keep the error in oxygen determinations below 0.25 or for the determination of all the gases in 1 c.c. of blood or the determination of carbon monoxide or nitrogen gas in the blood, the fine bore Van Slyke apparatus is desirable. Two cubic centimeters or more of blood are introduced into a separatory funnel or bottle and distributed in a thin layer about the inner wall, so that maximum contact with the air and complete saturation of the hemoglobin with oxygen are assured. The vessel is rotated for a few minutes to keep the blood in a thin layer or it may be shaken for 15 minutes or more by a mechanical shaker. The saturated blood is transferred to a heavy test tube or cylinder. The apparatus is thoroughly washed out twice with water to be sure to remove any alkali left from previous C02 determinations. For 2 c.c. of blood, 6 c.c. of distilled water instead of the original .004 per cent ammonia solution, 0.3 c.c. of 1 per cent saponin (Merck) solution and 2 or 3 drops of redistilled caprylic alcohol PHYSIOLOGIC CHEMISTRY METHODS 217 are introduced into the apparatus and freed of air. After the mixture has been introduced into the 50 c.c. chamber of the ap- paratus, the chamber is evacuated by placing a drop of mercury in the capillary and allowing it to run as far as the cock in order to seal it after the water mixture has run in; then the mercury bulb is lowered and hung at position 3 and the mercury in the pipette is allowed to fall to the 50 c.c. mark and the lower cock is closed as the mercury exactly reaches the mark; the apparatus is then un- clamped and turned upside down 15 or more times or shaken for 15 minutes to extract the aii' in the vacuum. The extracted air is expelled and the extraction repeated until no more air is left in solution. Nearly all of the 6 c.c. of air free water, saponin, alcohol solution is then forced up into the cup. The blood which has not or has been aerated is stirred to assure even distribution of corpuscles, and drawn into a pipette calibrated to deliver 2 c.c. between two marks, the lower of which is 3 or 4 cm. from the tip. The pipette is introduced under the water solu- tion in the cup, so that the tip rests on the bottom near the capil- lary. As the blood flows out of the pipette held in the left hand, the stopcock is partially opened with the right hand, so that the blood accompanied by some of the water flows at once on into the chamber of the apparatus. The layer of blood need never rise more than 1 or 2 mm. above the bottom of the cup and the slight amount adhering is washed completely into the chamber by the water solution which follows after all the blood has been de- livered. Before the last c.c. of water solution is readmitted, 0.10 to 0.12 c.c. (or three drops from a dropper which delivers 1 c.c. in 25 to 30 drops) of a solution containing 20 gm. of potassium ferri- cyanide per 100 c.c. is added and introduced into the chamber with the last of the water solution after the blood. A mercury seal is made and the apparatus is evacuated and shaken for 3 minutes. Continue the extraction in each case for a sufficient period to insure its completion. When extraction is complete, the vacuum is released by opening the lower cock, and the mercury together with the reaction mixture is allowed to run up into the chamber of the apparatus. Normally 2 c.c. of blood yield about 0.50 c.c. of O2, 0.015 c.c. of N,, and 0.2 c.c. of CO2; about % of the total blood CO, is evolved under the conditions of the analysis. 218 METHODS IN MEDICINE To absorb the CO2 the leveling bulb is lowered so that the level of the mercury in the bulb is slightly below the level in the ap- paratus, thus producing a slight negative pressure in the apparatus. Five-tenths c.c. of 0.5 N. NaOTI solution, previously saturated with air or oxygen is admitted from the cup of the apparatus and allowed to trickle slowly down the inner wall to absorb the CO2 from the gas mixture. If a solid column of alkali forms in the tube, a little mercury run in will dislodge it, and by being coated with alkali hasten the absorption of CO2 to completion. The drop of mercury insures against an error from the small amount of alkali which usually remains just below the stopcock even when all the alkali solution appears to flow down the sides of capillary pipette. Time must be allowed for the drainage down of the alkali solution before the reading is taken. The extracted solution in the bulb is then trapped below the lower cock by running it through the lower stopcock into the right hand lower chamber, taking care that no gas follows. The mercury bulb is raised and the lower cock is turned to connect the pipette with the lower left chamber. The mercury rises in the pipette body and calibrated stem to the level of the gas extracted from the solution. The surface of the mercury in the leveling bulb is made to correspond with the surface of the mercury in the pipette. The volume of gas is then read on the pipette scale. When the reaction mixture is left in the main chamber of the apparatus, the surface of the mercury in the leveling bulb must be raised sufficiently above that in the apparatus to balance the column of water solution in the latter. The Stadie empirically calibrated scale attached to the holding stand facilitates accurate pressure adjustment. The scale is calibrated by placing 8 c.c. of water, the amount equal to the final volume of the reaction mixture, in the chamber of the gas apparatus. With the upper cock of the apparatus open to establish atmospheric pressure within, mark on the scale the levels at which the surface of the mercury in the leveling bulb is held when 0.10, 0.20, 0.30, etc., c.c. of gas are present in the apparatus. Tn analyses subsequently the leveling bulb height is adjusted by comparison with the scale. Calculations.-Table III on page 219 contains all the data required in routine work. Oxygen Combined with Hemoglobin in Blood Artificially Saturated PHYSIOLOGIC CHEMISTRY METHODS 219 Table III Factors for Calculating Results from Analysis of 2 o.c. of Blood Saturated with Air AIR. PHYSICALLY DISSOLVED BY 2 C.C. FACTOR BY WHICH CORRECTED BLOOD. SUBTRACT FROM GAS VOLUME GAS VOLUME IS MULTIPLIED TO READ IN ORDER TO OBTAIN CORRECTED GAS GIVE VOLUME, REPRE- SENTING 0o SET GLOBIN CALCU- FREE FROM HEMO- FACTOR BY WHICH 0 X Y G E N L A T E D ON T H E GLOBIN GAS MEASURED AT T°C CHEMI- BASIS OF ZO.H PER AND BMM. PRESSURE CALLY BOUND CENT OXYGEN. COR- IS REDUCED TO O°C BY 100 C.C. RESPONDING TO 1OO AND 7 00 MM. HG. BLOOD PER CENT HEMO- GLOBIN c.° C.C. C.C. C.C. Per cent B B* B . -■ 1 ■ 15 0.037 0.932 X 760 46.5 x 760 222 x 760 16 0.036 0.928 X 46.3 x ( ( 221 x " 17 0.036 0.924 X ' ' 46.0 x (( 220 X ' 18 0.035 0.919 X 45.8 x ( c 219 X 1 ' 19 0.035 0.915 X 45.6 x ( c 218 X ' 20 0.034 0.910 X 1 45.4 x C 6 217 X ' ' 21 0.033 0.906 X " 45.1 x C C 216 X ' ' 22 0.033 0.901 X 44.9 x C ( 214 X 23 0.032 0.897 X ' ' 44.7 x C C 213 X 24 0.032 0.892 X ' ' 44.4 x ( ( 212 X " 25 0.031 0.888 X ' ' 44.2 x c c 211 X ' ' 26 0.030 0.883 X 44.0 x c c 210 X ' ' 27 0.030 0.878 X ' ' 43.7 x c c 209 X 'c 28 0.029 0.873 X 43.5 x (( 208 X 29 0.029 0.868 X ( ' 43.3 x ( c 207 X ' 1 30 0.028 0.863 X ' ' 43.1 x c c 206 X '* B = Barometric reading. with Air (Oxygen Capacity of Blood).-In determining the oxygen capacity (usually as a measure of the hemoglobin content) blood is saturated with air at room temperature, as described. From the total N2 + O2 obtained on extraction of blood thus saturated, it is necessary to deduct N, and the physically dissolved O2. According to Bohr (1905) the solubility coefficient of oxygen in blood is 0.031 at 15°, 0.022 at 38°. For the usual room temperature, range of 15 to 25°, the coefficient varies from 0.031 to 0.027, with a mean of 0.029 at 20°. The volume per cent of oxygen physically dis- solved by blood equilibrated with atmospheric air at 20°, 760 mm. 17 may therefore be estimated as 100 x 0.029 x 0.209 x 760 -ygg = 0.59. At 25° the figure would be 0.55, at 15° it would be 0.63. 220 METHODS IN MEDICINE The figure thus calculated from the solubility coefficient may, as in the case of nitrogen, not be exact, but it does not appear prob- able that the error, if there is one, is large enough to be significant. If we add the figure for oxygen dissolved at 20° to the empirically determined nitrogen content saturated with air at room tempera- ture we have 0.59 + 1.52 = 2.11 volumes per cent of physically dissolved O2 + N2 to subtract from the total O2 + N2 content in order to obtain the oxygen combined with hemoglobin. When the total O2 of the saturated blood is determined directly, by absorption with pyrogallol, correction is to be made only for the 0.59 volume per cent of physically dissolved oxygen. In Table I of the original article (Van Slyke, 1918) the volume of ''dissolved air" to be subtracted from blood shaken at 20° was calculated, from the solubility coefficient of air, to be 0.034 c.c. This corresponds to 0.031 c.c. measured at 0°, or 1.55 volumes per cent of the 2 c.c. of blood analyzed, a figure 0.55 volume per cent below that based on the nitrogen content which we find by actual analysis. Consequently oxygen capacities calculated as outlined in the original paper have been approximately 0.55 volume per cent too high. This corresponds to an error of plus 0.41 gm. of hemoglobin per 100 c.c. of blood, or plus 3.0 per cent of the average normal hemoglobin content. References: Butterfield, E. E.: Ztschr. f. Physiol. Chem., 1909, Ixii, 173. Palmer, W. W.: Jour. Bioh Chem., 1918, xxxiii, 119. Van Slyke, D. D.: Jour. Biol. Chem., 1918, xxxiii, 127. Van Slyke, D. D., and Stadie, W. C.: Jour. Biol. Chem., 1921, xlix, 1. A SYSTEM OF BLOOD ANALYSIS Folin and Wu Methods I. Precipitation of Blood Protein.- (Use Folin and Wu pipette.) (Emil Greiner Co., N. Y.) 1. Transfer a measured amount of blood (5, 7, 9, 10 or 12 c.c.) into a flask having a capacity 15 to 20 x that of the volume taken. 2. Dilute with 7 volumes of water and mix. (Measure with a cylinder.) 3. With an appropriate pipette add 1 volume of 10 per cent solu- tion of sodium tungstate (Na2 W.0.4 2H,O) and mix. 4. With another suitable pipette add to the contents in the flask (with shaking) 1 volume of 2/3 N. sulphuric acid (H2SO4). PHYSIOLOGIC CHEMISTRY METHODS 221 5. Close the mouth of the flask with a rubber stopper and give a few vigorous shakes. (If conditions are right hardly a single air bubble will form as a result of shaking.) When properly coagulated, the coagulum gradually changes from pink to dark brown in color. If this does not occur, the coagula- tion is incomplete, practically always due to too much oxalate or citrate. Use only 20 mgm. of potassium oxalate per 10 c.c. of blood. Avoid citrate, whenever possible. If used add the minimum amount. In incomplete coagulation, add 2N. H2SO4 drop by drop, shaking vigorously after each addition and allowing the mixture to stand for a few minutes before adding more, until complete. 6. Pour the mixture on a filter large enough to hold the entire contents of the flask and cover with a watch-glass. If filtration is begun by pouring the first few c.c of the mixture down the double portion of the filter paper and withholding the remainder until the whole filter has been wet, the filtrates are al- most invariably as clear as water from the first drop. If not clear return first 2 to 3 c.c. to the funnel. (Use filter paper of 11, 12%, 15, and 18% cm. diameters. The filtrate should be negative or at the most just perceptible when tested with Congo Red Paper (10 c.c. requiring 2 c.c. of 0.1 N. NaOH,; to preserve filtrate more than 2 or 3 days add 1 to 2 drops of Toluene or Xylene). Sodium tungstate (Primos Pa. Chemical Co.). Carbonate con- tent is important, therefore titrate 10 c.c. of a 10% solution plus one drop of phenolphthalein with 0.1N. HC1. 1 c.c. HC1 = 1.06% Na2CO3. The amount of acid should not exceed 0.4 % ; otherwise more H2SO4 is necessary in (4) to free the whole tungstic acid with 10% excess and a large part of the uric acid will be lost. Determination of Nonprotein Nitrogen Acid Digestion Mixture.- Mix 300 c.c. phosphoric acid syrup (85% H3P04) 100 c.c. concen- trated sulphuric acid. Transfer to a tall cylinder, cover well, and set aside for sedi- mentation of calcium sulphate. In 7 to 10 days the top part is clear and 50 to 100 c.c. can be removed by means of a pipette. 222 METHODS IN MEDICINE To 100 cc. of clear acid, add 10 c.c. of 6% copper sulphate solution and 100 c.c. of water. Nessler Solution.- The stock solution of mercuric potassium iodide. Dissolve 150 gm. of potassium iodide in 100 c.c. of warm water. Add 200 gm. of mercuric iodide (stir until dissolved). Dilute to 1 liter, filter if necessary, dilute to 2 liters. New Process, if mercuric iodide is not high grade. Transfer 150 gm. of potassium iodide and 110 gm. of iodine to a 500 c.c. Florence flask. Add 100 c.c. of water and an excess, 140-150 gm. of metallic mercury. Shake the flask continuously and vigorously for 7 to 15 minutes, or until the dissolved iodine has nearly disappeared. The solution becomes quite hot. When the red iodine solution has begun to become visibly pale though still red, cool in running water and continue the shaking until the reddish color of the iodine has been replaced by the greenish color of the double iodide. The whole op- eration should consume not more than 15 minutes. Decant the sur- plus mercury and wash with liberal quantities of distilled water. Dilute the solution and washings to a volume of 2 liters. If the cooling is begun in time, the resulting reagent is clear enough for immediate dilution with 10 per cent alkali and water and the fin- ished solution can at once be used for nesslerizations. Final Nessler Solution: from stock solutions. From completely saturated NaOH sol. (55 gm. per 100 c.c.) de- cant the clear supernatant solution. Dilute to a concentration of 10% (determine by titration that error is less than 5%). Introduce 3,500 c.c. of 10% NaOH into a large bottle. Add 750 c.c. of the double iodide solution and 750 c.c. of distilled water. Total 5,000 c.c. Nessler's solution. 223 PHYSIOLOGIC CHEMISTRY METHODS Concise Description of the Determination.- 1. Introduce 5 c.c. of protein free filtrate into a dry 75 c.c. pyrex ignition test tube graduated at 35 c.c. and at 50 c.c. 2. Add 1 c.c. sulphuric-phosphoric acid digestion mixture. 3. Add a dry quartz pebble and boil vigorously for 3 to 7 min- utes over a microburner until the characteristic dense acid fumes begin to fill the tube. 4. When the fumes are unmistakable, cut down the flame so that the contents are just visibly boiling, close the mouth of the tube with a watch crystal. 5. 'Continue heating for 2 minutes from the time the fumes be- gan to be unmistakable, even if solution is clear or colorless within 20 to 40 sec. If not clear and colorless in 2 minutes, continue until nearly colorless; almost invariably the process is complete in one minute. 6. Allow contents to cool for 70 to 90 seconds and then add 15 to 25 c.c. of water. 7. Cool further, approximately to room temperature and add water to 35 c.c. mark. 8. Add, preferably with a pipette, 15 c.c. of the Nessler's solu- tion. Insert a clean rubber stopper and mix. 9. If turbid, centrifuge a portion before comparison with the standard. Standard.- 0.3 mg. of N. (in the form of ammonium sul- phate) in a 100 c.c. flask. Add 2 c.c. of the sulphuric-phosphoric acid mixture. 50 c.c. water. 30 c.c. Nessler's solution. Fill to the mark and mix. Nesslerize Unknown and Standard at the same time. 10. If Standard is set at 20 mm. for the color comparison, 20 di- vided by the reading and multiplied by 30 equals mg. N.P.N. per 100 c.c. Determination of Urea 1. Transfer 5 c.c. of the tungstic acid blood filtrate to a clean and dry 75 c.c. Pyrex ignition tube (be sure that the tube has not 224 METHODS IN MEDICINE contained Nessler solution and that the latter has not been removed with nitric acid). 2. Add 2 drops of pyrophosphate solution. 140 gm. sodium pyrophosphate (U.S.P.). 20 gm. glacial phosphoric acid. Water to 1000 c.c. 3. Then add 0.5 to 1 c.c. Urease solution. Prepare as follows: Place in a 200 c.c. flask or bottle 3 gm. permutit. Wash by decan- tation once with 2 per cent acetic acid and twice with water. To the moist permutit in the flask add 100 c.c. of 30 per cent alcohol (35 c.c. of 95 per cent alcohol mixed with 70 c.c. of water). Then introduce 5 gm. of Jack bean meal and shake for 10 min. Filter and collect the filtrate in 3 or 4 small clean bottles. This is serviceable for 1 week at room temperature or 3-5 weeks if on ice. 4. Immerse test tube in a beaker of warm water for five min- utes. The temperature of bath should not exceed 55° C. Warmth is preferable, not essential; if in cold continue for 10 to 15 minutes more. 5. Distil the ammonia into 2 c.c. of 0.05 N. HC1 in a 2nd test tube. Use rubber stoppers with delivery tube through the stoppers. The second test tube may be lighter in weight and graduated at 25 c.c. The delivery tube must reach below the surface of the HC1 (see original article). 6. Add to hydrolyzed blood filtrate a dry pebble, 2 c.c. saturated borax solution and a drop or two of paraffin oil. 7. Insert firmly the rubber stopper carrying both delivery tube and receiver and boil moderately fast over a microburner for 4 minutes. The size of the flame should never be cut down during the distillation, nor should the boiling be so brisk that emission of steam from the receiving tube begins before the end of 3 minutes. After 4 minutes slip up the delivery tube and boil for 1 more min- ute. Rinse off with distilled water. 8. Cool the distillate with running water; dilute to about 20 c.c. 9. Add 2.5 c.c. of the Nessler solution. 10. Fill the receiving tube to 25 c.c. mark and compare in the PHYSIOLOGIC CHEMISTRY METHODS 225 colorimeter with a standard containing 0.3 mg. of N in 100 c.c. flask and nesslerized with 10 c.c. of Nessler solution. Nesslerize Unknown and Standard simultaneously. Calculation. Multiply 20 (the height of the standard in mm.) by 15 and divide by the colorimetric reading to get the Urea nitro- gen per 100 c.c. blood. Urea Determination by Urease and Aeration 1. Decompose urea, as described, in a pyrex test tube. 2. One or 2 c.c. 10 per cent NaOH. 3. Aspirate the ammonia into a test tube graduated at 25 c.c. and containing 2 c.c. of 0.05 N. HC1. Precaution: Rinse all rubber tubing with water before using, to remove any talcum or ammonia. Urea Determination by Autoclave Decomposition 1. Take 5 c.c. blood filtrate in a 75 c.c. test tube. 2. Add 1 c.c. of normal acid. 3. Cover mouth of tube with tin foil. 4. Heat contents in the autoclave at 150° C. for 10 min. 5. Allow autoclave to cool to below 100° C. before opening. 6. Ammonia is then distilled off exactly as in the first process described except that 2 c.c. of 10 per cent Na2CO3 are substituted for the borax. 7. Ammonia may be removed by aeration in the usual manner. Determination of Creatinine and Creatine Standard Solution.- Suitable for creatinine and for creatine determinations. Transfer to a liter flask 6 c.c. of standard creatinine solution used for urine analysis (containing 6 mg. of creatinine). Add 10 c.c. N. HC1; dilute to liter mark with water and mix. Transfer to a bottle and add 4-5 drops of toluene or xylene. 5 c.c. equals 0.03 mg. creatinine plus 15 c.c. wa- ter equals Standard ordinarily. 10 c.c. of Standard plus 10 c.c. water gives a range of 2-4 mg. 15 c.c. of Standard plus 5 c.c. water gives a range of 4-6 mg., etc. 226 METHODS IN MEDICINE Preformed Creatinine Determination.-To a clean flask. Transfer 25 (or 50) c.c. of a saturated solution of purified pic- ric acid. Add 5 (or 10) c.c. of 10 per cent NaOH and mix. Transfer 10 c.c. of blood filtrate to a small flask or to a test tube. Transfer 5 c.c. of Standard Solution and dilute standard to 20 c.c. Add 5 c.c. of freshly prepared alkaline picrate solution to the blood filtrate. Add 10 c.c. of freshly prepared alkaline picrate solution to the diluted creatinine solution. Let stand 8-10 min. and make color comparison. Complete comparison within 15 minutes. Calculation. Reading of standard in mm. (usually 20) multi- plied by 1.5, 3, 4.5 or 6 (according to amount of standard taken) divided by the reading of the Unknown in mm. equals mg. of Cre- atinine per 100 c.c. Creatine Plus Creatinine Determination.- Transfer 5 c.c. of blood filtrate to a test tube graduated at 25 c.c. Add 1 c.c. N. HC1. Cover the mouth of the test tube with tin-foil and heat in the autoclave to 130° C. for 20 min. or 155° C. for 10 min. Cool, add 5 c.c. alkaline picrate solution; let stand 8-10 min., then dilute to 25 c.c. The Standard Solution required is 10 c.c. of creatinine solution in a 50 c.c. volumetric flask. Add 2 c.c. of normal acid and 10 c.c. of alkaline picrate solution and after 10 min. standing dilute to 50 c.c. The standard is usually prepared first so that it is at hand. Calculation.-Reading of standard (usually 20) divided by read- ing of the Unknown and multiplied by 6 gives the "total creatin- ine" in mg. per 100 c.c. Normal equals 6 mg. per 100 c.c. In uremic bloods, etc., dilute the filtrate. Determination of Uric Acid Folin's Latest Modification Use lithium oxalate, 1 mg. per c.c. of blood as the anticoagulant. Lithium oxalate cloth is prepared as follows: 75 to 80 grams of starchfree bird's eye cotton cloth is cut into strips about 10 cm. wide and 50 cm. long. These are to be impregnated with lithium PHYSIOLOGIC CHEMISTRY METHODS 227 oxalate, 10 grams of lithium carbonate and 17 grams of oxalie acid are dissolved in 240 c.c. of hot water (75° C.). The warm solution is transferred to a plate, and the cotton strips are passed through it and hung upon a string to dry. The cloth when dry will carry about 20 per cent lithium oxalate. Fifty mg. of such cloth will easily prevent clotting in 15 to 20 c.c. of blood. Solutions: Uric Acid Standard Solution.-Transfer exactly one gram of uric acid to a funnel on a 300 c.c. flask. Transfer from 0.45 to 0.5 gram of lithium carbonate to a 300 c.c. beaker, add 150 c.c. of water and heat to 60° C. shaking or stirring until all the carbonate has dissolved. With the hot carbonate solution rinse the gram of uric acid into its flask and shake. The uric acid dissolves promptly and the clear solution is shaken and cooled under running water and transferred to a volumetric liter flask. Rinse the original flask and add the rinsings and water diluting the volume to 400 or 500 c.c. Add 2'5 c.c. of 40 per cent formaldehyde solution and after shaking to insure thorough mixing acidify with 3 c.c. of glacial acetic acid or equivalent quantities of 50 per cent or 25 per cent acetic acid. Shake to remove most of the carbonic acid, dilute to volume and mix. Fill up to the neck a series of 100 c.c. or 150 c.c. bottles with the stock solution, stopper very tightly, label and keep in a dark place. For actual use the standard stock solution con- taining 1 mg. per c.c. is diluted 250 times, then 5 c.c. contain 0.02 mg. To prepare this diluted standard transfer 1 c.c. of the stock standard uric acid formaldehyde solution containing 1 mg. per c.c. to a 250 c.c. volumetric flask. Half fill the flask with water and add 10 c.c. of the 2/3 N sulfuric acid used in blood protein precipita- tion. Add also 1 c.c. (but no more) of 40 per cent formaldehyde and then dilute to volume, mix and date. This diluted standard keeps for at least five weeks. Uric Acid Reagent.-Latest Method for Preparing-Folin.- Transfer 50 c.c. of 85 per cent phosphoric acid and 160 c.c. of water to a 500 c.c. flask. Heat nearly to boiling and then add 3 00 g. of sodium tungstate. The mixture begins to boil from the heat of the reaction. Boil gently but continuously over a micro burner for 1 hour, using a 10 cm. funnel and a 200 c.c. flask filled with cold water as a condenser. 228 METHODS IN MEDICINE Transfer 25 g. of lithium carbonate to a liter beaker. Add 50 c.c. of 85 per cent phosphoric acid and 200 c.c. of water. Boil off the carbon dioxide and cool. Mix the two solutions and dilute to one liter. No additional lithium salt is used with this reagent, yet no tur- bidity is encountered; and the maximum color is obtained (with 1 c.c. of the reagent and 22 c.c. of 15 per cent sodium cyanide) up to 8 mg. of uric acid per 100 c.c. of blood-provided that the cyanide blank is negligible. Lithium Sulfate Solution.-Dissolve 20 grams of powdered lith- ium sulfate (Baker and Adamson's) in about 80 c.c. of cold water. Dilute to a volume of 100 c.c. and filter from the slight amount of insoluble matter present. Sodium Cyanide Solution.-Prepare a 15 per cent solution of white chemically pure sodium cyanide in 0.1 N sodium hydroxide. Transfer 100 to 450 grams of sodium cyanide to a large beaker, add 6.7 c.c. of 0.1 N sodium hydroxide for each gram of cyanide taken, stir occasionally until the whole has dissolved. Opalescence is due to the presence of a little insoluble matter. Bottle, label and let stand for two weeks or longer before using. It is best to prevent decomposition since its prevention is so easily accomplished. The use of 0.1 N or even 0.05 N, sodium hydroxide instead of water furnishes ample protection against decomposition. Prac- tically all freshly prepared cyanide solutions contain notable quan- tities of impurities as reducing substances, which give a blue color with the uric acid reagent. The reducing impurities in the cyanide solutions diminish spontaneously, at first rapidly, then more and more slowly and many weeks must elapse before they are entirely gone. In 2 to 3 weeks the impurities have diminished to such an extent that practically no color is obtained in the cold, and the color produced on heating, after standing for 2 minutes at room temperatures, is so small as not to interfere with the uric acid determination. The test for the blank due to impurities in the cyanide, is made as follows: Transfer 5 c.c. of water, 2 drops of lithium sulfate solution, and 2 c.c. of the 15 per cent cyanide solution to a test tube. Add 1 c.c. of the uric acid reagent, let stand for 2 minutes. The solution should remain colorless. Heat in boiling water for 1.5 minutes and cool; some color is obtained. To determine whether this color does or does not materially affect the uric acid values PHYSIOLOGIC CHEMISTRY METHODS 229 obtained in actual determinations repeat the test described-with two graduated test-tubes and with standard uric acid solution- 5 c.c. in one, and 3 c.c. plus 2 c.c. of water, in the other. Dilute to volume after heating and compare the colors. If the cyanide is perfectly good, the weaker solution will give the theoretical read- ing, 33.5 mm., when the stronger is set at 20 mm. The Silver Lactate Solution should be prepared as follows: Dis- solve 100 gm. of silver lactate in about 700 c.c. of warm water. To 100 c.c. of 85 per cent lactic acid add 100 c.c. of 10 per cent sodium hydroxide. Pour this partly neutralized lactic acid into the silver lactate solution, dilute to 1 liter, and set aside to allow the sediment, always present, to settle. Use only the clear super- natant solution. By thus neutralizing a part of the lactic acid, one provides for any excess acidity present in the blood filtrate and also for traces of mineral acids which may be present in some sam- ples of silver lactate or in the lactic acid. The Uric Acid Determination.- 1. Half fill a wide liter beaker with water and heat to boiling. 2. Transfer 5 c.c. of the blood filtrate and 2 c.c. of water to one test-tube graduated at the 25 c.c. mark. 3. Transfer 5 c.c. of the standard uric acid solution and 2 c.c. of water to another similar test-tube. 4. Add 2 or 3 drops of 20 per cent lithium sulfate solution to each. 5. From a burette add 2 c.c of the 15 per cent sodium cyanide solution. 6. By means of a 5 c.c. blood pipette, graduated in tenths, or another graduated pipette, add 1 c.c. of the uric acid reagent of Folin to each test-tube. Mix, let stand for 2 minutes. 7. At the end of two minutes transfer both test-tubes to the boiling water and leave them there for 80 seconds. 8. Cool, dilute to volume, and make the color comparison in the usual manner, not omitting first to read the standard against itself. When the standard is set at 20 mm. 20 divided by the reading of the unknown, times 4, gives the uric acid content in milligrams per 100 c.c. of blood. The proportionality of the color obtained is in this case so good, if the cyanide is right, that readings between 10 and 40 mm., covering a range of from 2 to 8 mg., are dependable. 230 METHODS IN MEDICINE 9. To isolate the uric acid from the blood filtrate, transfer from 2 to 5 c.c. (usually 5 c.c.) of the latter to a centrifuge tube. With a blood pipette, or a small cylinder, add 7 c.c. of the silver lactate solution. No stirring is necessary or desirable. Let settle for 1 or 2 minutes, and then centrifuge. All the uric acid, down to the last trace, will now be in the precipitate. 10. Decant the supernatant solution as completely as possible, and add 1 c.c. of a 10 per cent solution of sodium chloride in tenth normal hydrochloric acid. Stir thoroughly with a fine glass rod; add 4 c.c. of water and stir again. Centrifuge. 11. Pour the supernatant solution, which need not be perfectly clear, into a test-tube graduated at the 25 c.c. mark. 12. Transfer 5 c.c. of the standard uric acid solution to another similar test-tube. 13'. To the contents of each tube add 2 drops of lithium sidfate 2 c.c. of sodium cyanide, and 1 c.c. of the uric acid reagent. 14. Shake a moment and let stand for 2 minutes. 15. Then heat for 80 seconds, cool, dilute to volume, and make the color comparison and the calculation as in the direct method. Calculation.-(a) Filtrate taken = 2 c.c. blood. (b) Standard diluted 2 x unknown. (c) Standard contains 0.1 or 0.2 mg. uric acid. 20 x 25 divided by reading of unknown = mg. per 100 c.c. of uric acid content of blood with weaker standard set at 20 mm. Notes. A weaker standard may be prepared as follows: Transfer 1 c.c. of 10% sulphite solution 3' c.c. 20% sodium carbonate 2 c.c. acid sodium chloride 0.5 c.c. sodium cyanide, and 25 c.c. of weaker standard and dilute to 50 c.c. or Add 5 c.c. of 20% sod. carbonate to 25 c.c. of regular standard and dilute to 50 c.c. Invariably add uric acid reagent after, never before, the addi- tion of sodium carbonate, because in acid solution, sulphite gives blue color with phosphotungstic acid. PHYSIOLOGIC CHEMISTRY METHODS 231 The intensifying color effect of cyanide is lost, the antifading effect remains. Reference: Folin, Otto: Jour. Bio.-Chem., October, 1922, liv, 153, Personal Communica- tion. Determination of Amino-acid Nitrogen Solutions: Standard Amino-acid Solution.-Purify glycine by dissolving the amino-acid in distilled water and then precipitating with half to one volume of alcohol. Transfer to a 200 c.c. volumetric flask .075 gram of purified glycine, and 150 c.c. of N/10 hydrochloric acid. After the glycine has gone into solution add .4 gram of sodium benzoate and make up to 200 c.c. with N/10 hydrochloric acid. This solution contains .07 milligram of amino-acid nitrogen and will keep indefinitely. Sodium Carbonate Solution.-Dilute 50 c.c. of approximately saturated sodium carbonate solution to 500 c.c. Titrate the solution against 20 c.c. of N/10 hydrochloric acid with methyl red as the indicator. Dilute so that 8.5 c.c. of the alkaline solution neutralize 20 c.c. of the N/10 acid, thus making about a 1 per cent sodium carbonate solution. Sodium B-napthoquinone Sulphonate Solution.-Prepare freshly 100 mg. of the chemically pure salt dissolved in 20 c.c. of distilled water, thus making a fresh 5 per cent solution. The dry salt can be weighed out in 100 mg. amounts and placed in small flasks and kept in the dark. The fresh solution can be quickly prepared by the addition of the 20 c.c. of water to one of these flasks. Ques- tionably pure salts may be prepared according to directions given in the original article. Acetic Acid-Acetate Solution.-To 100 c.c. of 50 per cent acetic acid solution add 100 c.c. of 5 per cent sodium acetate solution. Sodium Thiosulphate Solution.-Dissolve 4 grams of the chem- ically pure salt in 100 c.c. of distilled water, thus making a 4 per cent solution. Phenolphthalein Solution.-Prepare a .25 per cent solution. The Amino-acid Nitrogen Determination.-Method of procedure. Five or preferably 10 c.c. of the tungstic acid filtrate are placed in a 30 c.c. or 25 c.c. graduated test tube. In a similar tube place 1 c.c. of the standard acid glycine solution and 3 c.c. or 8 c.c. of water. To each tube add one drop of the phenolphthalein solu- 232 METHODS IN MEDICINE tion. Add 1 c.c. of the 1 per cent sodium carbonate solution to the standard and to the unknown add the 1 per cent sodium carbonate solution, carefully drop by drop for 3 or 4 drops, until the pink color matches that of the standard. Add another 5 c.c. volume of water to the standard. Add 2 c.c. of the freshly prepared sodium B-naphthoquinone sul- phonate to the standard and 1 c.c. or 2 c.c. (if 10 c.c. of tungstic acid filtrate was used) to the unknown. Mix uniformly by slight shaking and set aside in complete darkness for 20 to 30 hours. Then add 2 c.c. of the acetic acid-acetate solution to the stand- ard and 1 c.c. or 2 c.c. to the unknown. Then add 2 c.c. of the sodium thiosulphate solution to the stand- ard and 1 c.c. or 2 c.c. to the unknown. Add 14 c.c. of water to the standard and 7 c.c. to the unknown if 5 c.c. of the tungstic acid filtrate had been taken,while if 10 c.c. the preferable amount had been used, dilute both the standard and the unknown to 25 c.c., mix and make comparisons in the colorim- eter with the standard at 20. To calculate the Amino-acid Nitro- 20 x 7 gen in mgm. per 100 c.c. = ==--> - - , v . The X (reading of the unknown) normal value for whole blood after a night's fast is 5.7 to 7.8 mg. with an average of 6.4 mg. Reference: Folin, O. and Wu. H.: Jour. Biol. Chem., 1922, li, 377. Determination of Chlorides The Folin and Wu tungstic acid filtrate was used by Gettler instead of the picric acid filtrate in the method of McLean and Van Slyke and Austin and Van Slyke. Whitehorn also uses the tungstic acid filtrate in the following method. Solutions: Standard Silver Nitrate (M/35.46).-Transfer 4.791 grams of chemically pure silver nitrate crystals to a liter flask, add dis- tilled water and when solution is complete fill to the mark with distilled water, mix thoroughly. One c.c. is equivalent to 1 mg. of chlorides. Preserve in a dark brown glass bottle. Potassium or Ammonium Sulphocyanate (M/35.46).-The stand- ard solution should be prepared volumetrically because the salts are hygroscopic. Dissolve 3 grams of potassium sulphocyanate or 2.5 grams of ammonium sulphocyanate in a liter of water. By PHYSIOLOGIC CHEMISTRY METHODS 233 titration and proper dilution the standard is prepared so that 5 c.c. are equivalent to 5 c.c. of the silver nitrate solution. Ferric Ammonium Sulphate Powder Indicator.-The powdered solid chemical facilitates solution and insures a high concentration of the indicator in the solution. Concentrated Nitric Acid (Sp. Gr. 1.42).-Any C.P. preparation. Method of Procedure.-Transfer 10 c.c. of the tungstic acid fil- trate into a porcelain dish. To this add with a pipette 5 c.c. of the standard silver nitrate solution, stir thoroughly to precipitate the chlorides. Then add about 5 c.c. of concentrated nitric acid, mix and let stand for 5 minutes to permit the blocking out of the in- soluble silver chloride. Then add with a spatula about 0.3 gram of powdered ferric ammonium sulphate indicator and mix thor- oughly. Then titrate the excess of silver nitrate with the stand- ard sulphocyanate solution until the definite salmon red (not yel- low) color of ferric sulphocyanate persists in spite of stirring for at least 15 seconds. To calculate the amount of chlorine 5.(c.c. of AgNO3 used) - X(c.c. KCNS or NH4CNS used) = mg. of Cl. per c.c. of whole blood or plasma. To express the chlorin value in terms of sodium chlo- ride divide by 0.606 or multiply by 1.65. The normal sodium chloride content of whole blood is from 450 to 520 mg. per 100 c.c., while in plasma the values are 570 to 620 mg. per 100 c.c. References: Whitehorn, J. C.: Jour. Biol. Chem., 1921, xlv, 449. Gettler, A. O.: Jour. Amer. Med. Assn., 1921, Ixxvii, 1650. Determination of Sugar Molybdate Phosphate Solution.- Transfer to a liter beaker 35 gm. of molybdic acid 5 gm. of sodium tungstate 200 c.c. of 10% sodium hydroxide 200 c.c. of water. Boil vigorously for 20-40 min. to remove nearly the whole of the ammonia present in the molybdic acid. Cool, dilute to about 350 c.c. and add 125 c.c. of concentrated phosphoric acid (85%). Dilute to 500 c.c. 234 METHODS IN MEDICINE Alkaline Copper Solution.- Dissolve 40 gm. of pure anhydrous sodium carbon- ate in 400 c.c. of water, transfer to a liter flask. Add 7.5 gm. of tartaric acid and when dissolved Add 4.5 gm. of crystallized copper sulphate. Mix and make up to a volume of 1 liter. If chemicals are impure a sediment of cuprous oxide may form in 1 to 2 weeks; if so remove the clear supernatant reagent with a siphon or filter through good quality filter paper. The reagent seems to keep indefinitely. To test for absence of cuprous copper, take 2 c.c. and add 2 c.c. of molybdate phosphate solution. The deep blue color of copper should almost completely vanish. Standard Sugar Solutions (3).- (1) Stock solution 1 per cent dextrose or invert sugar preserved with xylene or toluene or best benzoic acid .25%. (2) Solution 1 mg. per 10 c.c. (5 c.c. of stock solution diluted to 500 c.c.). (3) Solution 2 mg. per 10 c.c. (5 c.c. of stock solution diluted to 250 c.c.). Use special constricted blood sugar test tubes (Emil Greiner Co., N. Y.). Latest modifications, larger model with graduations for dilution of unknown to as nearly as possible the shade of the standard (see Evans, F. A., Rothberg, V. E., and Mason, T. M., Tr. Am. Soc. Clin. Invest., Jour. Am. Med. Assn., 1923). Method.- 1. Transfer 2 c.c. tungstic acid blood filtrate to a constricted or narrowed blood sugar test tube. 2. To two similar test tubes graduated at 25 c.c. add 2 c.c. of standard sugar solution (0.2 and 0.4 mg. dextrose). 3. To each tube add 2 c.c. alkaline copper solution. The sur- faces of the mixtures must now have reached the constricted por- tion of the tube. If the bulb is too large for the volume (4 c.c.) a little but not more than 0.5 c.c. of diluted (1:1) alkaline copper solution may be added. If too large or too small a bulb, (over or under 4 c.c.) discard. 4. Transfer the tubes to a boiling water-bath and heat for six (6) minutes. PHYSIOLOGIC CHEMISTRY METHODS 235 5. Then transfer the tubes to a cold water-bath and let cool without shaking for 2-3 minutes. 6. Add to each test tube 2 c.c. of molybdate phosphate solution. Cuprous oxide dissolves rather slowly if the amount is large but the whole, up to the amount given by 0.8 mg. of dextrose, dissolves usually within 2 minutes. 7. When the cuprous oxide is dissolved, dilute the resulting blue solutions to the 25 c.c. mark, insert a rubber stopper and mix (adequate attention must be given to getting blue color out of the bulb). 8. Two standards 0.2 mg. and 0.4 mg. are adequate with a range from 70 mg. to nearly 400 mg. of glucose per 100 c.c. Cooling in stage 5 is not absolutely necessary. Standards and unknown should be heated the same length of time and should have substantially the same temperature when the acid reagent is added. With the large graduated tube dilute unknown to first match standard roughly. The maximum color develops faster in hot solutions but with uniform conditions color comparisons may be made at the end of an hour as well as within five minutes. The depth of the standard (in mm.) multiplied by 100 and di- vided by the reading of the unknown, gives the sugar content in mg. per 100 c.c. of blood. References: Folin and Wu: Jour. Biol. Chem., 1919, xxxviii, 81. Ibid., 1920, xli, 36G. The Determination of Blood Sugar Shaffer-Hartmann Method Principle.-Remove protein by tungstic acid according to Folin- Wu directions. Heat blood filtrate with alkaline copper solution in water-bath or over microburner. The amount of copper reduced to cuprous oxide by the oxidation of the sugar is determined by reoxidizing it to cupric salt by a known excess of iodine by the following reversible reaction: 2 Cm + + 2 I- <-> 2 Cm + I2 The presence of oxalates forms complex salts with cupric ions and by reducing their concentration the equilibrium is shifted to the left of the equation, and the excess of iodine is titrated with stand- 236 METHODS IN MEDICINE ard thiosulphate. The iodine necessary for the oxidation of cu- prous salt as well as the oxalate is contained in the copper reagent which is made up as follows: CuSO4 .5H2O 5.0 gm. NaoCO.3 anhyd. 40.0 gm. Tartaric acid 7.5 gm. Rochelle salt 10.5 gm. KT 10.0 gm. KIO3 0.7 gm. Potassium oxalate 18.4 gm. Water to make 1000.0 c.c. Dissolve the Na2CO3 in about 400 c.c. warm water. Dissolve CuSO4 and tartaric acid in about 150 c.c. warm water and pour into carbonate solution with stirring. Dissolve iodide, iodate and oxalate (neutral) in about 200-300 c.c. warm water and rinse into carbonate. Cool and dilute to a liter. The 0.005 N thiosulphate used for the titration should be made up and standardized in 0.1 N strength. Na2S2O3.5H2O, 24.8 gm., is dissolved to 1 liter and standardized by means of potassium bichromate, permanganate or biiodate. Twenty-five c.c. of the standardized 0.1 N solution is diluted to 500 c.c. every few days as needed. A few drops of NaOH to both solutions protects from decomposition by carbon dioxide of the air. Method.-Measure a known amount of oxalate blood (1 c.c. to 5 c.c.)into a small flask and add seven volumes of water. After taking, add one volume of 10 per cent sodium tungstate (pure) and after mixing one volume of two-thirds normal sulphuric acid, stop- per the flask. Shake well and after 5 minutes filter. This is the Folin-Wu blood filtrate. Measure 5 c.c. equivalent to 0.5 c.c. of blood into a large test tube (20 x 200 mm.) and add 5 c.c. (accu- rately measured) of the copper reagent. Cover the tube by a small inverted beaker or bottle cap and place in a boiling water- bath for 15 minutes. (Or heat to boiling over a microburner and boil 2% minutes). Cool for 2 to 3' minutes under running water, add 1 c.c. 5 NH2SO4 (or 5 c.c. N), and titrate with 0.005 N thio- sulphate adding starch toward the end. The end point is sharp and permanent. Subtract the titration from the "Blank" on the reagent which is determined (only occasionally) after heating the reagent with water instead of blood filtrate. The blank titration will be about PHYSIOLOGIC CHEMISTRY METHODS 237 20 c.c. 0.005 thiosulphate and need be redetermined only after about two months' time. The difference between the blank and the titration of a determi- nation, multiplied by the copper-factor of the thiosulphate used gives the copper reduced. One c.c. 0.005 N. thiosulphate = 0.318 mg. Cu. Consult the fol- lowing table for the conversion of copper into terms of glucose. The table gives also data from which the difference in titration in c.c. 0.005 N. thiosulphate for 5 c.c. Reagent + 5 c.c. blood filtrate may be converted directly into percentage sugar in blood. Determination of Sugar in Blood 5 c.c. Reagent 5 c.c. Blood Filtrate cu. MG. MICROBURNER 2J/2 MIN. GLUCOSE % IN MG. BLOOD WATER-BATH 15 MIN. GLUCOSE % IN MG. BLOOD THIOSUL- PHATE C.C. 0.005 N PER CENT GLUCOSE IN BLOOD MICRO- WATER- BURNER BATH 0.4 .26 .051 .24 .048 1.0 .043 .042 0.5 .30 .060 .29 .058 1.5 .058 .056 0.6 .34 .068 .33 .066 2.0 .072 .069 0.7 .39 .078 .37 .074 2.5 .086 .082 0.8 .43 .086 .41 .082 3.0 .100 .096 0.9 .48 .096 .45 .090 3.5 .114 .109 1.0 .52 .104 .50 .100 4.0 .128 .122 1.1 .57 .114 .54 .108 4.5 .143 .135 1.2 .61 .122 .58 .116 5.0 .157 .149 1.3 .66 .132 .62 .124 5.5 .171 .163 1.4 .70 .140 .66 .132 6.0 .185 .176 1.5 .75 .150 .70 .140 6.5 .198 .189 1.6 .79 .158 .75 .150 7.0 .212 .202 1.7 .83 .166 .79 .158 7.5 .227 .216 1.8 .88 .176 .83 .166 8.0 .242 .230 1.9 .92 .184 .88 .176 8.5 .258 .243 2.0 .97 .194 .91 .182 9.0 .270 .256 2.2 1.05 .210 1.00 .200 9.5 .284 .269 2.4 1.14 .228 1.08 .216 10.0 .298 .282 2.6 1.23 .246 1.17 .234 10.5 .313 .295 2.8 1.32 .264 1.25 .250 11.0 .324 .309 3.0 1.41 .282 1.33 .266 11.5 .346 .322 3.2 1.50 .300 1.42 .284 12.0 .368 .335 3.4 1.58 .316 1.49 .298 12.5 .380 .348 3.6 1.65 .330 1.56 .312 13.0 .395 .361 3.8 1.84 .368 1.62 .324 13.5 .407 .374 4.0 1.91 .382 1.69 .338 14.0 .419 .387 4.3 2.04 .408 1.88 .376 14.5 .396 4.6 2.15 .430 1.98 .396 15.0 .404 Reference: Shaffer, P. A., and Hartmann, A. F.: Jour. Biol. Chem., Jan., 1921, xlv, 349, 365. 238 METHODS IN MEDICINE Purification of Picric Acid For Blood Sugar Methods Test for Purity.- Samples of picric acid vary widely in purity. To 20 c.c. of saturated (1.2 per cent solution) of picric acid add 1 c.c. of 10 per cent sodium hydrate, let stand for 15 minutes. The color of the alkaline solution should not be over twice that of saturated solution. If picric acid is very pure, the color of picrate solution will be 1% times that of the acid solution. If the quality of the picric acid is good, the color of the picrate solution will be no deeper at end of 24 hours than at end of 15 minutes. To Purify.- Place 600 gm. of wet picric acid into a flask (4 L.). Pour on boiling water until flask is almost full and add 200 c.c. of saturated (50 per cent) sodium hydrate. Stir and if necessary heat again until all the picric acid is dissolved. To the hot picrate solution add slowly 200 gm. of sodium chloride. Cool to 30°. Filter on a large Buchner funnel and wash a few times with 5 per cent NaCl solution. Transfer to the flask again, add boiling water, when the picrate is dissolved add 50 c.c. of 10 per cent sodium hydrate and then 100 gm. sodium chloride as before. Repeat this process twice more (4 x) but for the last washing use distilled water. Dissolve the purified picrate in a large flask with boiling distilled water and filter hot on a folded filter, collecting the filtrate. To the hot filtrate add 100 c.c. of cone, sulphuric acid diluted previously with 2 volumes of water. The liberated picric acid comes out at once. Cool to 30°. Filter with suction and wash free of sulphates with distilled water. Reference: Folin, O., and Doisy, E. A.: Jour. Biol. Chem., 1917, xxviii, 349. The Estimation of Blood Sugar Myers and Bailey Modification of "The Lewis-Benedict Method" Principle.-Dextrose, picric acid, and sodium carbonate give a red color due to formation of picramic acid. Method.- Withdraw 2.5 c.c. of blood and oxalate it. PHYSIOLOGIC CHEMISTRY METHODS 239 Take 2 c.c. of the well mixed oxalated blood with an Ostwald pipette and dilute with 8 c.c. water in a centrifuge tube. Allow the corpuscles to lake and then add 0.2 gm. dry picric acid. After thoroughly mixing centrifuge and filter. Place 3 c.c. of filtrate (0.6 c.c. blood) in a narrow 20 c.c. test tube. Add 1 c.c. 20 per cent Na2CO3 and boil tube and its contents 15 minutes in a beaker of boiling water. Cool the filtrate and dilute to 10, 15, or 20 c.c. according to color. The Standard Solution.- .100 gm. picramic acid. .2 gm. of sodium carbonate in 30 c.c. warm water. Dilute to 1000 c.c. Or: 3 c.c. of a 0.2 per cent sugar solution in saturated picric acid solution, and 1 c.c. of 20 per cent sodium carbonate heated. 3 c.c. standard = .006 gm. or 0.6 per cent. reading standard \z dilution of unk. „ . -p-5 iA ,. x--= % of blood sugar reading unknown dilution ot stand. or grams per 100 c.c. Reference: Myers, V. C., and Bailey, C. V.: Jour. Biol. Chein., 1916, xxiv, 147. Estimation of Blood Sugar Lewis and Benedict Method Aspirate 2 c.c. of blood with an Ostwald pipette and needle with rubber tubing attachment. (Powdered potassium oxalate in the tip of pipette prevents clotting.) Or take 2 c.c. of oxalated blood. One drop of commercial formalin (40 per cent) per 5 c.c. of blood is known (Denis and Waddell) to prevent glycolysis for four days. Discharge the contents of the pipette into a 25 c.c. vol. flask containing 5 c.c. water. Rinse the pipette twice with distilled water. Complete hemolysis should occur promptly. Fifteen c.c. of saturated aqueous solution of picric acid or (B) Sodium picrate solution (36 grams of dry picric acid dissolved in 500 c.c. 1 per cent NaOH and 400 c.c. hot water added, cooled, and 240 METHODS IN MEDICINE diluted to 1000 c.c.) are added and a drop or two of alcohol to dispel foam. Make up to mark with water or (B) the sodium picrate solution, and shake. Protein precipitation should be complete in three min- utes. Filter. Duplicates of 8 c.c. each are placed in large test tubes. Add 2 c.c. of saturated solution of picric acid and exactly 1 c.c. of a 10 per cent solution of sodium carbonate. (Also 2 glass beads and 2 drops of mineral oil). Evaporate over a free flame until a precipitate occurs. Add about 3 c.c. water and heat to boiling to dissolve precipitate. Transfer to a 10 c.c. volumetric flask, cool, fill to mark, shake, and filter through cotton into a colorimeter chamber. Standard Picramic Solution (A). Picramic acid .064 gm. Sodium Carbonate .100 gm. Water to 1000 c.c. If the (B) sodium picrate solution has been used the method is carried on in the following simple way: To the 8 c.c. of filtrate in the volumetric flask add 1 c.c. of the carbonate solution [20 gm. Na2C'O3 (anhydrous) made up to 100 c.c. with distilled water]. Place in boiling water until the color develops (10 min. at least). Make up to 12.5 or 25 c.c. according to which matches the standard nearest. Dissolve picramic acid in 25-50 c.c. water by heat. The water is made alkaline with the sodium carbonate. Cool and make to liter. Standard Picramic Solution (B) is made up as follows: Picramic acid 100 mg. and sodium carbonate 200 mg. dissolved in 1000 c.c. distilled water as the stock solution. The working stand- ard consists of 126 c.c. of this stock solution together with 1 c.c. 20 per cent sodium carbonate solution, and 15 c.c. of the sodium picrate solution diluted to 300 c.c. with distilled water. To check the Standard A. .64 mgm. dextrose. 5 c.c. saturated picric acid. 1 c.c. 10 per cent sodium carbonate evaporated and made up to 10 c.c. PHYSIOLOGIC CHEMISTRY METHODS 241 To check the Standard B. .64 mg. glucose C.P. in 4 c.c. distilled water plus 1 c.c. 20 per cent sodium carbonate, plus 4 c.c. sodium picrate. Boil 10 minutes. Dilute to 12.5 c.c. and match with the standard. Calculation A: 2 c.c. blood to 25 c.c. of which 8 c.c. were taken 8/25 x 2/1 = .64 c.c. of blood used. Therefore, mgm. dextrose in unknown = reading standard , . ,, , , 77 , x (K gm. dextrose m the standard) reading unknown Or , reading standard Mg. dextrose per c.c. blood = , x reading unknown Mg. dextrose in Standard c.c. of blood used. But there are .64 mg. dextrose in the standard and .64 c.c. of blood were used. Therefore, Mgm. dextrose per 100 c.c. blood = reading standard -, x 1000. reading unknown Calculation B: reading standard , • 77 , 7- 10 = per cent ot sugar m the unknown, reading unknown Reference: Lewis, R. C., and Benedict, S. R.: Jour. Biol. Chem., 1915, xx, 61. Determination of Fatty Acids and Cholesterol Solutions: Alcohol-Ether Mixture, (3 to 1). Mix 300 c.c. of redistilled ab- solute alcohol and 100 c.c. of redistilled anhydrous ether. Concentrated Sodium Hydroxide.-Collect the drippings from a stick of metallic sodium placed on an inverted watch crystal in an evaporating dish, and exposed to the water vapor atmosphere of distilled water in a desiccator. Dilute Sulphuric Acid.-Dilute one volume 25 c.c. of concentrated sulphuric acid with three volumes 75 c.c. of distilled water. Dilute Hydrochloric Acid.-Dilute one volume 25 c.c. of concen- trated hydrochloric acid with three volumes 75 c.c. of distilled water. Chloroform.-C. P. neutral and free from water and alcohol. 242 METHODS IN MEDICINE Acetic Anhydride. Concentrated Sulphuric Acid. Standard Cholesterol Solution.-For the stock cholesterol solu- tion add 0.2 gm. of cholesterol to 200 c.c. of chloroform. To prepare the standard from this take 10 c.c. of the stock solution and add chloroform to 100 c.c. making the amount of cholesterol in 5 c.c. of the standard .5 mg. Standard Fatty Acid Solution.-Make a stock solution of 200 grams of oleic acid in 500 c.c. of 95 per cent redistilled alcohol and a stock solution of 200 grams of palmitic acid in 500 c.c. of 95 per cent redistilled alcohol. For the standard solution mix 60 c.c. of the stock oleic acid solution with 40 c.c. of the stock palmitic acid solution. This standard is such that 5 c.c. of the solution contains 2 mg. of a mixture of fatty acids. Method of Procedure.-Centrifuge 15 to 20 c.c. of oxalated blood and remove 5 c.c. of the plasma which is transferred drop by drop to a 100 c.c. flask containing 75 c.c. of the 3 to 1 alcohol-ether mixture. The flask is to be rotated rapidly and constantly while the plasma is slowly added. Continue the rotating while the solu- tion is brought to a boil in a water bath. Cool to room tempera- ture and make up to 100 c.c. with the 3 to 1 alcohol-ether mixture, shake up well and filter. Measure 10 to 20 c.c. of the filtrated into a 100 c.c. "Non sol" Erlenmeyer flask. Add 0.1 c.c. of the concentrated sodium hy- droxide solution. Evaporate on a water bath with occasional agita- tion until only a few drops of liquid remain and the odor of alcohol is no longer evolved. Partially neutralize the excess alkali by adding 0.1 c.c. of the dilute sulphuric acid solution, if necessary add a drop of distilled water to facilitate the mixing, sodium sul- phate is formed. Dry completely but carefully on the water bath. It is important to note that the amount of acid should be less than the amount necessary to neutralize the added alkali. Cholesterin is altered by heating in the presence of strong alkali. Overheating is also to be avoided. Separation and Determination of Cholesterol Cool the flask, add 10 c.c. of cold chloroform, allow to stand for 10 minutes with occasional shaking to facilitate extraction. Pour the chloroform extract through a 5.5 cm. hardened filter paper into PHYSIOLOGIC CHEMISTRY METHODS 243 a similar flask. Repeat the extraction twice with 5 c.c. volumes of chloroform, taking care not to dislodge any of the crystals from the original residue. The combined chloroform extract evaporated to 2 or 3 c.c. is put into a 10 c.c. glass-stoppered, graduated cylinder and the volume made up to 5 c.c. with chloroform washing. The extract may be slightly turbid but colorless. Measure 5 c.c. of the standard choles- terol solution (0.5 mg. in 5 c.c. chloroform) into the same type of glass cylinder. To bring out the color reaction add to each cylinder 1 c.c. of acetic anhydride and 0.1 c.c. concentrated sulphuric acid. Invert several times to mix and allow to stand for 15 minutes at 20° C. or room temperature and in the light in which the readings are to be made. Compare in a colorimeter equipped with the cups cemented with chloro-insoluble glue or plaster of Paris. The stand- ard is set at 15 mm. Calculations: (Standard Reading) 15 * (Cholesterol in Standard) .5 (Unknown Reading) x Volume of plasma used .5 mg. of cholesterol per 100 c.c. Determination of the Fatty Acids The residue in the original flask, following the chloroform ex- traction contains the fatty acids. To this residue add 10 c.c. of redistilled alcohol, heat to boiling on a water bath and boil for ten minutes. Pour the hot alcoholic solution through the small hardened filter paper previously used for the chloroform extract, into a 100 c.c. Erlenmeyer flask. Repeat the extracted once with 5 c.c. of alcohol and add this extract through the same filter. The combined alcoholic extracts are then evaporated on a water bath to a 2 or 3 c.c. volume. Transfer to a 10 c.c. glass-stoppered graduated cylinder, rinsing the flask with just enough alcohol to bring the volume to 5 c.c. To a 100 c.c. of distilled water in a 250 c.c. beaker, with constant stirring add the alcoholic extract through a small funnel with a long stem of narrow bore (1 mm.) the tip of which should extend to nearly the bottom of the beaker. Rinse the cylinder once with the suspension and pour back into the beaker through the funnel. The standard fatty acid solution (2 mg. in 244 METHODS IN MEDICINE 5 c.c.) is handled in the same way, exactly 5 c.c. being suspended in 100 c.c. of distilled water in a 250 c.c. beaker. To each of these beakers add with stirring 10 c.c. of the dilute hydrochloric acid. The solutions are then compared in a nephel- ometer in 3 to 10 minutes. The nephelometer should be checked each time with the standard. With tubes of 50 to 60 mm. depth fairly accurate results are obtained directly when the concentra- tions of the unknown and standard differ 20 per cent or less. With tubes of less depth, the range of accuracy is limited to differ- ences of 10 per cent or less. Calculate: Standard reading 30 Cone, of Fatty Acid in Standard 2.0 Unknown reading x Volume of blood 0.5 = mg. of fatty acid in 100 c.c. of blood. The method has about a 5 per cent error when all conditions are satisfactory. By these methods the normal whole blood contains 0.14 to 0.17 grams and the plasma 0.15 to 0.18 grams of cholesterol per 100 c.c., while the total fat content is 0.60 to 0.70 grams per 100 c.c. Reference: Bloor, W. R., Pelkan, K. F., and Allen, D. M.: Jour. Biol. Chem., 1922, cclxxi, 191. Determination of Blood Cholesterol Method of Myers and Wardell Reagents.- Calcium sulphate C.P. (calcined gypsum or plaster of Paris). Chloroform C.P. Acetic Anhydride C.P. and of good grade. Sulphuric Acid (Cone.) C.P. With a good grade of acetic anhydride, it has been found that when a 0.005 per cent solution of naphthol green B is used and this set at 15.5 mm. in the Duboscq or Kober colorimeter it matches almost absolutely 0.4 mg. of cholesterol in 5 c.c. of chloroform treated with 2 c.c. of acetic anhydride and 0.1 c.c. of concentrated sulphuric acid set at 15 mm. The color curves for both cholesterol and naphthol green B appear to fall in a straight line so that higher and lower PHYSIOLOGIC CHEMISTRY METHODS 245 readings are accurate. The cholesterol color fades rather rapidly after reaching its greatest intensity, while the naphthol green B, which matches the cholesterol color quite well, appears to be per- manent. Apparatus.- A colorimeter, preferably a Kober or Bock-Benedict. If the Duboscq type is used, the cups must be remounted in plaster of Paris instead of balsam. Extraction shells of paper 4 cm. long. Perforated glass tubes 2.5 x 7 cm. with numerous small holes in the sides and flat bottom. A small reflux condenser with a large cork on the bottom to attach the perforated glass tube to the condenser. A 150 c.c. extraction flask. A graduated pipette with 0.1 c.c. division. An electric hot plate. Method.-Pipette 1 c.c. of blood plasma or serum into a porcelain crucible or small beaker containing 4 or 5 grams of plaster of Paris. Stir and mix carefully and dry preferably in a drying oven for an hour. Then empty into a small paper extraction shell and insert into the short perforated glass tube. This perforated tube with its contents is attached to the large cork of the small reflux condenser and the tube and cork inserted in the neck of a 150 c.c. extraction flask containing about 20 to 25 c.c. of chloroform. Extraction is continued for 30 minutes on an electric hot plate. The chloroform is made up to some suitable volume, such as 20 c.c. filtered if necessary, and colorimetric estimation carried out in the following way: Five c.c. of the chloroform extract are pipetted into a dry test tube and 2 c.c. of acetic anhydride and 0.1 c.c. of concentrated sulphuric acid are added. After thorough mixing, the solution is placed in a dark cool place, or in fresh tap water in a dark place for 10 minutes to allow the color to develop. The unknown is then prepared colorimetrically with a standard 0.005 per cent aqueous solution of naphthol green B. If a cholesterol standard containing 0.4 mg. of cholesterol in 5 246 METHODS IN MEDICINE c.c. of chloroform solution, or a naphthol green B standard of equal strength, are employed, the following formula may be used for the calculation. S 1) - x 0.0004 grams x - x 100 = cholesterol content of blood in per IF O cent. S stands for the depth of the standard in millimeters. R stands for the reading of the unknown in millimeters. 0.0004 the equivalent amount of cholesterol in 5 c.c. of chloroform. D. the dilution of the chloroform extract from 1 c.c. of blood. 5. the dilution of the standard. 100 the factor for 100 c.c. References: Myers, V. C., and Wardell, E. L.: Jour. Biol. Chenn, 1918, xxxvi, 149. Myers, V. C.: Jour. Lab. and Clin. Med., 1920, v, 780. Solutions: Copper Sulphate, 20 per cent. Dissolve 200 grams of CuSO4, 5H2O in distilled water and make up to 1 liter. Mercuric Sulphate, 10 per cent. Dissolve 73 grams of pure red HgO in 1 liter of 4N H2SO4. Sulphuric Acid, 50 vol per cent. Dilute 500 c.c. of H2SO4 of 1.835 specific gravity to 1 liter with water. If necessary readjust concentration by titration to make 17 N H2SO4. Calcium Hydroxide Suspension, 10 per cent. Suspend 100 grams of Ca(OH)2, (Merck's fine light "reagent" grade) in 1 liter of water. Potassium Dichromate, 5 per cent. Dissolve 50 grams K2Cr2O7 in water and make up to 1 liter. Combined Reagent for Total Acetone Body Estimation.- One thousand c.c. 50 per cent H2SO4, 3,500 c.c. HgSO4, 10,000 c.c. distilled water. Preparation of Protein Free Blood Filtrate.-For whole blood dilute 10 c.c. with 100 c.c. of water in a 250 c.c. flask, and add 10 c.c. of the 10 per cent mercuric sulphate solution. Agitate until the protein coagulates and fill the flask to the mark. Allow to stand for about 15 to 30 minutes and filter through a dry folded filter. In the case of plasma or serum take 8 c.c. and dilute with 30 to 40 c.c. of water and add 15 c.c. of the ten per cent mercuric Determination of Acetone Bodies PHYSIOLOGIC CHEMISTRY METHODS 247 sulphate. Agitate by gently shaking until the flocculent coagulin forms and then add water to the 250 c.c. mark. Method of Procedure: To remove interfering substances such as glucose, etc., take 125 c.c. of the above filtrate corresponding to 5 c.c. of blood in a 250 c.c. volumetric flask and add 100 c.c. of water and 50 c.c. of copper sulphate solution. Mix well and add 50 c.c. of 10 per cent calcium hydroxide suspension, and test with litmus. If necessary add more calcium hydroxide to make the reaction alkaline to litmus. Fill to the mark and decant for 30 minutes for the precipitation of glucose which may be removed by filtering through a dry folded paper. The filtrate should be sugar free and not show a precipitation of yellow cuprous oxide on boil- ing. In the precipitation of the blood proteins, the same reagent is used as in the precipitate of the preformed acetone and that of the acetic acid, and the excess of mercury would on heating tend to partly precipitate the acetone before it volatilized, and escaped. Therefore, a separation by fractional precipitation must be carried out especially if it is desired to determine separately in a single blood filtrate, both the acetone plus acetoacetic acid, and the B-hydroxybutyric acid. Transfer 25 c.c. of the sugar free filtrate to a 500 c.c. Erlenmeyer flask, and add 100 c.c. of distilled water, 10 c.c. of the 50 per cent sulphuric acid and 35 c.c. of the 10 per cent mercuric sulphate, or instead of all of these add 145 c.c. of the ' ' Combined Reagent." A mercury acetone precipitate forms as the first fraction contain- ing the preformed acetone, and that from the acetoacetic acid. Filter off the precipitate and save for weighing and titration. In the determination of the Total Acetone Bodies this filtration is not done, the precipitate is carried along through the next process. Receive all of the filtrate of this mercury acetone precipitate in 160 a dry flask. Place 160 c.c. equivalent to-- - x 5 c.c. of blood, in 170 a 500 c.c. Erlenmeyer flask, and add 30 c.c. of water. Connect the flask with an 8 to 10 mm. straight tubed reflux condenser, heat to boiling, and add through the condenser tube 5 c.c. of 5 per cent potassium dichromate. Continue boiling gently for an hour and a half, simultaneously oxidizing and precipitating, thus separating the yellow mercury sulphate-chromate compound of the acetone from the oxidation of the B-hydroxybutyric acid. 248 METHODS IN MEDICINE The precipitates are collected in Gooch "medium density" alun- dum crucibles, which have been previously washed with 200 c.c. of cold water, and dried for an hour at 110°. The crucible is allowed to cool in the room air. The crystalline precipitates are quickly dried and easily weighed. When facilities for weighing are absent the precipitates can be dissolved in dilute hydrochloric acid and then the excess titrated with potassium iodide. Solution of the Precipitate and Titration The contents of the Gooch crucibles including the asbestos are washed into small beakers with as little water as possible and 15 c.c. of normal hydrochloric acid are added. The mixture is heated and the precipitate promptly dissolves. When the alundum crucible is used it is set into the beaker of acid until the precipi- tate dissolves and then the crucible is washed with suction and the washings added to the beaker. When titration is used, one may dispense with the Gooch or alundum crucible, and wash the precipitate directly without suc- tion, on a small quantitative filter paper, which is transferred with the precipitate to the beaker and broken up with a rod in 15 c.c. of normal hydrochloric acid. Solution Used in Titration.- 3.M Potassium Acetate Solution. 0.2M Potassium lodid Solution. 0.05M Mercuric Chloride Solution, standardized by the sulphide method. Twenty-five c.c. of the 0.05 M HgCl2 are measured with a volumetric pipette and diluted to 100 c.c. with distilled water. H2S is bubbled through until a black precipitate flocculates and leaves a clear solution. The HgS collected in a Gooch crucible and dried at 110° should weigh 0.2908 grams if the solution is accurate. The mercury content of the precipitate has been found by gravi- metric analyses of the basic mercuric sulphate-acetone precipitate, and by titration has been found to average 76.9 per cent. On this basis each c.c. of 0.2 M KI solution being equivalent to 10 mgm. of mercury is equivalent to 13 mgm. of the mercury-acetone precip- itate. The 0.2 M KI solution is standardized by titration against the 249 PHYSIOLOGIC CHEMISTRY METHODS 0.055 HgCl, solution, such that 1 c.c. of the bichloride solution is equivalent in titration to exactly 1 c.c. of the iodide solution. The bichloride solution should be gravimetrically standardized and used for checking the iodide solution as the reverse would introduce a slight error. The reaction utilized is Hg Cl2 + 4 KI = K2Hg I4 + KOI Titration To insure a good clear encl-point, the acidity of the hydrochloric acid solution is reduced by the addition of excess 7 c.c. of 3 M potassium acetate solution to the cooled solution of the redissolved precipitate. Then the 0.2 M KI is run in rapidly from a burette with constant stirring until it is in excess. If more than a small amount of mercury is present, a red precipitation of Hgl2 forms at once and redissolves as soon as 2 or 3 c.c. of iodide solution, in excess of the amount required to form the soluble K2HgI4, have been added. If only a few milligrams of mercury are present, the excess of the iodide solution may be added before the red precipi- tate of Hgl2 has had time to form so that the titration solution remains clear. In any case, not less than 5 c.c. of the 0.2 MKI are added as the final titration has been found unsatisfactory if less is present. The excess of the iodide solution is titrated back by adding 0.05 M HgCl2 from another burette until a permanent red precipitate forms. Titration is not quite so accurate as weighing but except when the amounts determined are very small, the titration is satisfactory. One milligram of B-hydroxybutyric acid yields 8.45 mg. of pre- cipitate. One mg. of acetone yields 20.0 mg. of precipitate. One c.c. of 0.2 M KI solution is equivalent to 13 mg. of precipitate in titration of the latter. Table Factors for Calculating Results when Filtrate Equivalent to 5 c.c. of Blood is Used for Determination DETERMINATION ACTONE BODIES CALCULATED AS GRAMS ACETONE PER LITER OF BLOOD, INDICATED OF BY 1 gm. of precipitate 1 c.c. of 0.2 KI Sol. Total Acetone Bodies 12.8 0.161 Beta-hydroxybutyric acid 13.2 0.72 Acetone plus acetoacetic acid 10.0 0.130 Normal blood yields 13 to 26 mg. of total acetone bodies per 100 c.c. 250 METHODS IN MEDICINE Determination of Urinary Acetone Bodies In the quantitative determination of the acetone bodies in the urine the procedure is only slightly modified. Twenty-five c.c. of urine is taken instead of the whole blood or blood plasma, and diluted with water and the glucose and other interfering substances removed in the same way described for 125 c.c. of blood or plasma filtrate. The procedure will remove only 8 per cent of sugar, consequently urine containing more than 8 per cent must be diluted down to this concentration. The determination of total acetone bodies can be carried out just as described for the blood filtrate, using, however, 25 c.c. of the glucose free urine filtrate, and no separation of the mercury- acetone precipitate from that obtained following the addition of the dichromate and the heating in the reflux condenser, is carried out as described when it is desired to obtain from one blood sample both the preformed acetone plus that from acetoacetic acid and that from B-hydroxybutyric acid. The acetone plus the acetoacetic acid, which completely decom- composes into acetone and CO2 on heating, is determined without the B-hydroxybutyric acid exactly as the total acetone bodies, except that (1) no dichromate is added to oxidize the B-hydroxybutyric acid and (2) the boiling must continue for not less than 30 nor more than 45 minutes. Boiling for more than 45 minutes splits off a little acetone from B-hydroxybutyric acid even in the absence of chromic acid. The B-hydroxybutyric acid alone is determined exactly as total acetone bodies except that the preformed acetone and that from the acetoacetic acid are first boiled off. To do this, the 25 c.c. of urine filtrate plus 100 c.c. of water are treated with 2 c.c. of the 50 per cent sulphuric acid and boiled in the open flask for 10 minutes. The volume of solution left in the flask is measured in a cylinder. The solution is returned to the flask, and the cylinder washed with enough water to replace that boiled off and restore the volume of the solution to 127 c.c. Then 8 c.c. of the 50 per cent sulphuric acid and 35 c.c. of mercuric sulphate are added. The flask is connected under the condenser and the determination is continued as described for total acetone bodies. PHYSIOLOGIC CHEMISTRY METHODS 251 Table Special Factors for Calculation of Results when 25 c.c. of Urine Filtrate Equivalent to 2.5 c.c. of Urine, are Used for the Determination DETERMINATION PERFORMED ACETONE BODIES, CALCULATED, AS GM. ACETONE PER LITER OF URINE, INDICATED BY 1 c.c. of 0.2 MKI Sol. Total acetone bodies 24.8 0.322 B-hydroxybutyric acid 26.4 0.344 Acetone-acetoacetic acid 20.0 0.260 In order to calculate the acetone bodies as B-hydroxybutyric acid rather than acetone, use the above factors multiplied by the ratio of the molecular weights B-acid 104 1 o acetone 58 In order to calculate the acetone bodies in terms of molecular concentration, divide the factors in Table VIII by 58. To calculate c.c. of 0.1 M. acetone bodies per liter of urine use the above factors multiplied by --0,000 = 172.4 58 The normal urinary output of acetone bodies per day averages 3 to 15 mg. of acetone plus acetoacetic acid (about 25 per cent of which is acetone) and 20 to 30 mg. of B-hydroxybutyric acid. References: Van Slyke, D.D.: Jour. Biol. Chem., 1917, xxxii, 455. Van Slyke, D. D. and Fitz, R.: Jour. Biol. Chem., 1917, xxxii, 495. Determination of Chlorides in Blood or in Exudates or Transudates Method of McLean and Van Slyke (see also page 232) Principle.-The chlorides are precipitated in the presence of nitric acid by standard silver nitrate solution, the silver chloride is removed by filtration, and the excess of silver is titrated back with standard potassium iodide solution. The titration is performed in the presence of nitrous acid and starch, so that the first drop of iodide in excess of the silver present is changed to free iodine and gives the blue starch-iodine color. The optimum acidity for the end-point is fixed by the addition of the trisodium citrate in amount equivalent (J/3 molecule) to the free nitric acid present. 252 METHODS IN MEDICINE Note: Caution use of Chloride Free oxalate and filter paper. The Solutions required are: I. An acid solution of silver nitrate, 1 c.c. of which is equivalent to 2 mg. of NaCl. This solution contains 5.812 gm. of silver nitrate and 250 c.c. concentrated nitric acid (sp. gr. 1.42) in one liter. II. A solution of potassium iodide, 1 c.c. of which is equivalent to 1 mg. of NaCl. This solution contains 3' gm. potassium iodide per liter. III. A solution containing sodium citrate, sodium nitrate and starch, which substances respectively regulate the acidity, provide an oxidizing agent for the iodide and serve as indicator. This solution contains 446 gm. of trisodium citrate, 20 gm. of sodium nitrate and 2.5 gm. of soluble starch per liter. First dissolve the starch in about 500 c.c. of boiling water. Add citrate and nitrite and heat mixture until all is dissolved. Filter the solution while still hot through cotton, wash the filter with hot water, cool, and finally make up to a volume of 1,000 c.c. Standardize solution II against solution I by adding 5 c.c. of the latter to 5 c.c. of solution III and titrating with solution II until the blue end point is obtained. On the basis of this titration dilute the iodine solution to such a degree that 10 c.c. is exactly equivalent to 5 c.c. of the silver solution. As a preliminary step to the titration of chlorides in the blood, or other albuminous fluids, the protein must first be removed. This is accomplished as follows: Run 2 c.c. of oxalated blood from an Ostwald pipette into 10 c.c. of a 10 per cent magnesium sul- phate or better into 3 c.c. freshly made up 25 per cent meta- phosphoric acid solution contained in a 20 c.c. volumetric flask. Rinse the pipette twice by drawing up into it the solution from the flask. Add 2 drops of 50 per cent acetic acid, fill to the mark with water, invert a few times to secure a thorough mixing of its contents, and finally place for 10 minutes in a beaker of boiling water. After cooling pour the contents of the flask into about 3 gm. of Merck's blood charcoal in a small beaker. Let stand a few minutes and filter. A water clear filtrate should be obtained, which is now ready for titration. The final titration of the protein free filtrate (equivalent to 1 c.c. of blood). Carry out as follows: Pipette 10 c.c. of filtrate physiologic chemistry methods 253 (equivalent to 1 c.c. of blood) into a 25 c.c. volumetric flask. Add 5 c.c. of the silver nitrate solution and fill to the mark with dis- tilled water. Mix, allow to stand five minutes, and filter through a dry paper or better still centrifugate. Pipette 20 c.c. of this filtrate into a 50 c.c. Erlenmeyer flask, add 4 c.c. of Solution III and then run in potassium iodide (Solution II) from a burette until the end point is reached. The first definite blue color marks the end point and with practice is easily determined. The results may be calculated from the following formula when 20 c.c. of filtrate from the silver chloride is titrated. „ ,T ™ 12.8 (8 c.c. KI sol used) Grams NaCl per liter = - -- c.c. filtrate (from charcoal) used. Before beginning work it is desirable to make sure that the chem- icals employed (esp. the magnesium sulphate, potassium nitrite, charcoal, potassium oxalate or citrate and the filter paper) are free from chlorides. Before making up Solution III it is also well to deter- mine whether the soluble starch provided gives a blue end point with iodine. Much of the soluble starch on the market is so highly dextrinized that it gives a reddish-brown color with iodine and is therefore unfit for titration work. Free chemicals of chlorides by washing and recrystallization. Reference: McLean, F. C., and Van Slykc, D. D.: Jour. Biol. Chem., 1915, xxi, 3G7. Microdetermination of Blood Calcium Method of G. W. Clark Reagents.-Citrate Solution.-Saturated sodium citrate solution of pH 7-4 is used for citrating whole blood. One c.c. of this solu- tion containing approximately 900 mg. is used for each 100 c.c. of whole blood. Potassium Permanganate, Approximately 0.01 N.-Dissolve the salt in the required amount of water, and heat the solution on a steam bath for thirty-six to forty-eight hours or allow to stand at room temperature for ten to twenty-two days. The solution is then filtered through asbestos which has been digested with aqua regia to avoid the reducing action of organic material and washed free of chlorides, and is stored in amber bottles well protected from dust. The standardization is best made with sodium or cal- 254 METHODS IN MEDICINE cium oxalate; standard samples of the sodium oxalate are obtain- able from the Bureau of Standards, Department of Commerce, Washington, D. C. The oxalates are dissolved in, and made up to volume with, approximately N - H2SO4. Small portions of 5 to 10 c.c. are measured into a 50 c.c. centrifuge tube heated to 75° C. and titrated. These acid oxalate solutions, if carefully protected from dust, etc., may be kept for several months even to two years and used for subsequent titrations. Sulphuric Acid, Approximately N.-Add 28 c.c. of concentrated chemically-pure sulphuric acid to 970 c.c. of distilled water. Ammonium Chloride. One Per Cent Solution.-Test for the pres- ence of contaminating calcium by placing 10 grams in a platinum dish and applying sufficient heat to volatilize the ammonium chlor- ide. The ash is dissolved in a minimum amount of hot calcium- free 6 N. HC1 and the calcium precipitated by the Halverson- Bergeim modification of McCrudden's method. In any micromethod, especially in the determination of small amounts of calcium, sodium, etc., it is necessary to carefully test the reagents used. The modified method above mentioned is used in many calcium methods. The following directions are given for the testing and preparing of the necessary calcium-free reagents. Sodium Acetate 20 Per Cent Solution.-Make qualitative tests and select the lot of this reagent showing the smallest amount of cal- cium. Dissolve 200 grams of the crystalline salt in nearly the re- quired 1000 c.c. of distilled water, add 0.5 per cent of ammonium oxalate dissolved in a minimum amount of distilled water, and bring the solution to the total volume of 1000 c.c. If possible, place the solution in a refrigerator at 10-12° C. and allow it to stand for 48 hours, stirring it thoroughly once or twice each day. Cen- trifuge or filter through doubly washed (HC1 & HF) paper, and store in paraffine coated bottles. Dilute Hydrochloric Acid.-Evaporate almost to dryness 25 c.c. of the concentrated acid in a platinum dish and test for calcium. Evaporation to one drop is done, this is diluted to 5 c.c. and the calcium is precipitated in the regular way. Ammonium Hydroxide, Approximately 2N.-Evaporate 25 c.c. of concentrated ammonia in a platinum dish and test for calcium. Many C.P. ammonia samples were found by Clark to contain cal- 255 PHYSIOLOGIC CHEMISTRY METHODS cium. This reagent is best prepared by passing ammonia gas into conductivity water kept at a low temperature by an ice pack and in a container with sufficient space allowed for the increase in volume. The strength is determined by titration and dilutions are made to the desired normality. The reagent is stored in par- affin coated containers. Apparatus Required.- Centrifuge, preferably an electric one with at least moderately high speeds. Centrifuge tubes of 50 c.c. capacity and made of the best pyrex glass, the tapering end being only 36 mm. long and rather blunt, thus assuring thick walls. Burette of 10 c.c. capacity, graduated in 0.02 c.c. and allowing for the estimation of 0.01 c.c. to meet the re- quirements of the Bureau of Standards. (These burettes may be obtained from Emil Greimer Co., New York.) Siphon.-(Halverson and Bergeim, Jour. Biol. Chem., 1917, xxxii, 159.) Method.- Whole Blood.-Take 5 c.c. of the whole blood in standard citrate solution with a pipette and place in a 25 c.c. volumetric flask; with the same pipette add two 5 c.c. portions of warm water about 65° C. and mix; allow to stand 20 minutes or longer. Add 5 c.c. of 1 per cent ammonium chloride (the necessity of this reagent is not established), make up to volume with distilled water, mix thoroughly, and transfer to a 50 c.c. centrifuge tube. Cover the tube with a rubber dam or paraffined paper (to pre- vent evaporation and to keep out dust) and centrifuge at high speed for 20 minutes, slow down very gradually to prevent the dispersion of the light stroma. The deep red supernatant liquid must be clear. With a pipette remove 15 c.c. or, if possible, 20 c.c., transfer to a 50 c.c. centrifuge tube and while rotating the tube to agitate liquid, slowly add 4 c.c. of 3 per cent ammonium oxalate; mix thoroughly and allow to stand overnight. Rub down the walls of the tube with a rubber policeman, wash the policeman with a small amount of distilled water, and centri- 256 METHODS IN MEDICINE fuge at moderate speed (1,800 R.P.M.) until the solution is clear, which is within 5 minutes usually. Completely remove the supernatant liquid by siphon action, stir up the precipitate with a fine stream of cold distilled water, wash down the walls of the tube, using in all approximately 35 c.c. of water. Centrifuge immediately and siphon off completely the wash water. Dissolve the precipitate in 5 c.c. of approximately normal H,SO4, heat to 75° C. and titrate with 0.01 normal potassium per- manganate. The end point in the titration of calcium oxalate obtained by direct precipitation, especially from whole blood, is not so per- manent as in the case of pure inorganic solutions, and the amount of permanganate needed for the blank is greater. In order to decide upon a reproducible end point, it is advisable for each technician to practice by making a series of preliminary deter- minations. Average blank determinations on nonoxalated blood by Clark showed: (1) Whole blood - 0.10 c.c. of 0.01 N. potassium permanganate. (2) Plasma - 0.08 c.c. of 0.01 N. potassium permanganate. (3) Sulphuric acid 0.05 c.c. of 0.01 N. potassium permanganate. (5 c.c. of N.) The standard potassium permanganate solution is run in moder- ately rapidly from a 10 c.c. burette graduated to 0.01 c.c. Shake moderately and use a white background. The end point is at- tained when a faint pink color persists for a minute or longer on gentle shaking and standing. With an uncontaminated pre- cipitate the end point will be sharp to .01 c.c. The burette reading should be corrected for the small amount of permanganate, the blank, required to titrate 5 c.c. of the H2SO4 to the same end point, etc. Calculation: 1 c.c. of 0.0133 N. potassium permanganate is equivalent to 0.267 mgm. of calcium. The exact factor for a given solution, as the 0.0100 N. potassium permanganate, must be determined by the standardization with the Bureau of Standard's standard preparations. Multiply the number of cubic centimeters used by this factor to obtain the amount of calcium in the 25 c.c. of filtrate. If blank on reagents PHYSIOLOGIC CHEMISTRY METHODS 257 is negligible, deduction is not necessary. Multiply by 28 to get mg. of Ca. per 100 c.c. of serum or plasma. Plasma or Serum.-Place 1 to 5 c.c. of citrated plasma or serum in a 50 c.c. centrifuge tube and while rotating the tube slowly add 3' per cent ammonium solution, equal in volume to one-half the amount of serum or plasma. Mix thoroughly and allow to stand overnight. The remainder of the procedure is the same as that given above for whole blood. Reference: Clark, G. W.: Jour. Biol. Chem., Dec., 1921, xlix, 487. NORMAL VALUES IN BLOOD Chemical Determinations The normal values in blood chemical determinations are based on examinations of bloods taken after a twelve hour period of fasting. The values vary somewhat with the method used and consequently those of the standard Folin and Wu method and Folin's modifica- tions of this method are given. The figures of Hammeth are most closely followed. The amounts always indicate milligrams in 100 c.c. of blood. Nonprotein nitrogen 25. to 45. Average 35. Urea nitrogen 10. to 25. " 17 Amino-acid nitrogen 3. to 7. " 5. Uric acid 3.5 to 5. " 4.2 Creatinin 1. to 3.5 " 2.2 Creatin 2. to 9.5 " 6.0 Residual nitrogen 3.7 to 18.3 " 11.1 Sugar 85 to 160 Total acetone bodies 13 to 26 Cholesterol Whole blood 140 to 170 Plasma 150 to 180 Fatty Acids Plasma. 600 to 700 Chlorides Whole blood 450 to 520 Plasma 570 to 620 Carbon-Dioxide Combining Power 55 to 75 c.c. Oxygen Combining Power 20.9 c.c. CHAPTER XVIII ROUTINE BACTERIOLOGICAL AND SEROLOGICAL METHODS (Biological Laboratory of the Department of Internal Medicine) The following methods were outlined by Dr. Alan M. Chesney as a guide for those who are carrying out the routine work of the Biological Laboratory of the Department of Internal Medicine, Washington University School of Medicine. They represent the minimum of work required for each kind of examination. Collection of Material.-The laboratory staff is not expected to collect any material from the wards for examination except in the case of blood cultures, or in special cases where the laboratory staff definitely assumes the responsibility of collection. At the same time, in the interest of economy of labor, it is necessary to insist on the proper collection of specimens. For example, sputa for pneumococcus typing should represent lung exudate carefully col- lected in sterile containers and presented promptly, to a member of the laboratory staff. The same is true of sputa from which vaccines are to be made. Division of Work.-The technician in serology is responsible for the complement-fixation tests and for the issuance and filing of reports of same. The technician in serology must see that the animals used in such work are being cared for, and that the vari- ous reagents and the glassware are in sufficient supply and prop- erly prepared. Members of the house staff are not expected to do complement-fixations. The technician in bacteriology is in a general way responsible for the work, the methods, the reports and supplies. All diagnostic work must, however, be under the direct supervision of the assist- ant resident physician and the interne assigned to the laboratory. Verification of the technician's results is essential. The assistant resident physician is to have at his disposal such facilities as are desirable for any research in which he may be engaged, and besides this, he is to direct the work of the interne on duty in the laboratory. 258 ROUTINE BACTERIOLOGICAL AND SEROLOGICAL METHODS 259 The interne on duty in the laboratory is expected to avail him- self of the opportunity of learning clinical bacteriology. In order that his duties may have a definite basis, lie is held responsible for all specimens from the medical wards and out-patient department. If such work does not offer occasion for learning all routine bac- teriological methods, he is to he given such instruction by the assistant resident. Records.-Every specimen except blood for Wassermann or com- plement-fixation tests will be given a serial number as soon as received and entered in the ledger, together with appropriate in- formation (name, date, nature of material, result, name of examiner, and date reported). The slip accompanying the specimen will be saved and used for report. Specimens should not be accepted unless such a slip is presented with them. Duplicate cards will be filled out and filed at the same time the report is made. Each member of the laboratory staff must insist on having the proper data on the slip accompany- ing the specimen. Supplies.-Each worker is assigned to a desk which is reserved for him alone, lie is expected to have a full equipment of ap- paratus that shall be used by him alone. With this end in view a list of apparatus has been compiled which is designed to cover all the needs of the worker. He should see that he has this ap- paratus and if any articles are missing, should draw them from the stock room. List of material needed for workers in the Bacteriological Lab- oratory : Apparatus: Microscope, Mechanical Stage, Microscope Lamp, Bunsen burner, with pilot light, Test tube rack, Platinum wire, heavy, Platinum wire, medium, Luer syringes, 2 c.c., Luer syringes, 5 c.c., Luer syringes, 10 c.c., Pan for boiling instruments and syringes. Autopsy instruments as follows: 1 pr. scissors, small sharp pointed, 1 pr. scissors, large, 260 METHODS IN MEDICINE 1 scalpel, 1 pr. forceps, 1 artery clamp, small, Thumb tacks, Water-bath, File, Jar for pipettes, Jar for clean slides, Jar for cover-slips, Jar for dirty slides, Jar for infected hanging drop slides, Slides, Cover-slips, Waste water pan, Bottle distilled water siphon arrangement. Reagents as follows: Gentian violet (Sterling's or Carbol gentian violet), Carbol fuchsin, Methylene blue, Saffranin, Gram's iodine solution, Acid alcohol, Alcohol, Cedar oil and balsam. Disposal of Material.-Care should be taken in disposition of material to separate the infected from the uninfected, and each lot should be placed in its appropriate place on the table. If this is done there will be less danger to the laboratory attendants, and the work of cleaning glassware will be greatly expedited. Animals that have been autopsied may be wrapped in newspaper and placed in the large galvanized can that receives material for incineration. The cooperation of everyone in the laboratory is requested in helping to keep the laboratory a clean and satisfactory working place. Bacteriological Methods Where possible smears of specimens should be made and stained with appropriate methods. The evidence so obtained is often more important than the results of culture. Thus urines, throat swabs, sputums and exudates should have smears made at once. Sputum.-The specimen, which should have been collected in a sterile petri dish, is to be washed through six changes of sterile ROUTINE BACTERIOLOGICAL AND SEROLOGICAL METHODS 261 salt solution in petri dishes. It is then to be streaked out over the surface of blood agar plates. In streaking use a heavy plati- num wire or bent glass rod. The essentials of good technic are: (a) thorough washing, and (b) careful spreading. Do not use hemolysed blood plates. Pneumococcus Typing If the determination of the type of pneumococcus in the sputum is requested, the sputum should be carefully washed and about 0.5 c.c. injected intraperitoneally into a mouse. If the mouse ap- pears ill in six or eight hours its peritoneal cavity is punctured with a capillary pipette and the exudate withdrawn and stained with Gram's stain and a capsule stain. If pneumococci are numer- ous in the smear, kill the mouse; tack it to a board; open the peritoneal cavity with sterile instruments and: 1. Make cultures on agar and broth. 2. Wash out the contents of the cavity with sterile salt solution by means of a capillary pipette and transfer to a centrifuge tube. 3. Centrifuge at low speed for a few minutes to throw down cells, fibrin and debris. The bacteria will be left in the supernatant fluid. 4. Pipette supernatant fluid to another centrifuge tube, centri- fuge at high speed for 15 minutes. This will throw down the bacteria. Suspend sediment in salt solution and agglutinate with stock antipneumococcus serum as follows: Tube I Antipneumococcus Serum Type I (undiluted) 0.5 c.c. Tube II Antipneumococcus Serum Type II (undiluted) 0.5 c.c. Tube III Antipneumococcus Serum Type II (1 - 10) 0.5 c.c. Tube IV Antipneumococcus Serum Type III (undiluted) 0.5 c.c. Tube V Normal Horse Serum, undiluted 0.5 c.c. Tube VI Sterile Ox Bile .1 c.c. To each add 0.5 c.c. of suspension of the organism. Incubate in the water-bath at 37° C. and read at the end of one hour. If agglutination takes place in Tube I and in no other tubes, the organism belongs to Group I; if agglutination takes place in Tubes II and III and no other tubes, the organism belongs to Group IT; if in Tube II only and not in Tube III, the organism belongs to 262 METHODS IN MEDICINE one of the subgroups in Group II and is to be reported "Group II atypical." If agglutination takes place in Tube IV and in no other tubes, the organism belongs to Group III (pneumococcus mucosus). If there is no agglutination in any of the tubes, then the organism belongs to Group IV, provided it is- pneumococcus. Tube VI, which contains bile and test suspension is designated to show whether or not we are dealing with pneumococci, which are bile soluble. Pneumococci are dissolved by bile, hence, if the suspension consists of pneumococci only, this tube should appear entirely clear at the end of an hour. If it is not clear, then either there is a mixture of organisms in the suspension or else the or- ganisms are not pneumococci. If agglutination occurs in all the tubes, the organism is probably a streptococcus. When the mouse is autopsied cultures should be made from both peritoneal cavity and heart's blood on both blood agar plates and broth, in order that the agglutination on the suspension from the peritoneal cavity may be checked up with pure cultures of the peritoneal exudate along with the pneumococcus, and may in some instances mask the agglutination. Note: In using antipneumococcus serum for agglutination pur- poses the serum must be clear, as cloudy serum will mask the re- action. Since horse serum usually shows a precipitate, it may be necessary to clear this in the centrifuge. Tubercle Bacillus Culturing.- If cultures for tubercle bacillus are desired, use Petrotf's Method (see Hiss and Zinsser, Textbook of Bacteriology). Material should also be injected into the groin or the peritoneal cavity of two guinea pigs. These animals should be autopsied after six weeks and acid-fast stained smears made of any suspicious lesions. Throat Cultures.--Throat and nose cultures for B. diphtheriae are to be planted upon Loeffler's blood serum medium and smears are to be made at the same time and stained with methylene blue, counterstained by Gram's iodine. Whenever a smear is diagnosed for B. diphtheriae be sure to save the slides for future reference. Cultures from cases of acute tonsillitis should be planted on blood agar plates as well as Loeffler's blood serum medium. When cultures of the nasopharynx are made for the presence or absence ROUTINE BACTERIOLOGICAL AND SEROLOGICAL METHODS 263 of influenza bacilli, inoculation should be made on plain blood sugar plates in which the blood is not human blood, but preferably rabbit's blood. Subsequent transfers of suspicious colonies should be made to brown blood agar tubes or plates as the influenza bacillus grows more readily on this medium than on any other. Colonies of gram-negative diplococci should be transplanted on serum agar and their growth characteristics noted. If not typ- ically dry, or pigmented, and if they suspend uniformly in normal salt solution, they should be tested with antimeningococcus serum. This is done by mixing one-half c.c. of such serum diluted 1:50 with sterile normal salt solution, and one-half c.c. of a suspension of the culture, sufficiently turbid for a good agglutination test. A control tube is arranged in the same way with normal horse serum diluted 1:25. The tubes are then placed in water at 56° C. and allowed to remain overnight. The tubes must be stoppered with sterile cot- ton plugs. Positive reactions often occur in two hours. Stools.-As a rule stools are cultured for members of the typhoid- dysentery group only. For this purpose Kendall's modification of Endo's method is used. The principle depends upon the fact that the colon bacillus ferments lactose whereas the typhoid, para- typhoid and dysentery bacilli do not. In order to show that fer- mentation takes place an indicator (decolorized basic fuchsin) is used. In order to achieve success with this method two essential points must be observed: First, freshly prepared modified Endo's plates should be used and secondly, a good distribution of bacterial colonies on the plate must be obtained. To prepare modified Endo's plates, proceed as follows: Alelt up a flask of 100 c.c. 3 per cent meat extract agar. Add 1 per cent lactose. This will be found in the ice-box already sterilized. Each tube contains 1 gm. of lactose in solution and the contents of one tube must be added to every 300 c.c. of agar. Add also decolorized fuchsin solution. To prepare this, dissolve 0.1 gm. anhydrous sodium sulphite in a few c.c. of sterile distilled water and to this solution add 1 c.c. of a saturated alcoholic solution of basic fuchsin. The sodium sul- phite will be found sealed in ampules in the cupboard containing the glassware. The fuchsin is decolorized. Hot agar will give a rose pink color when the decolorized fuchsin is added, but this 264 METHODS IN MEDICINE color fades almost entirely when the agar cools. Allow agar to cool to about 45° before pouring plates. To secure good distribution three plates at least should be used. Make a dilute suspension of the feces in broth, allow to stand in incubator one hour, transfer a drop of the suspension to the first plate, spread this drop over the surface of the plate with a bent glass rod, or a heavy platinum wire, bent at a convenient angle. Rub the wire over the second and third plates without flaming and without touching the original drop. By this means a satis- factory distribution of colonies should be obtained on one of the three plates. Incubate for eighteen to twenty-four hours. On Endo's medium all lactose-fermenting bacteria produce red colonies or pink colonies with red centers, while nonlactose-fermenting bac- teria produce colonies which are grayish and opaque. Hence colon bacilli will give red colonies and typhoid, paratyphoid, and dysen- tery bacilli will give opaque or grayish colonies. Transfer sus- picious colonies to Russell's double sugar media, which will permit a tentative diagnosis of the suspicious organism. The following are the reactions given on Russell's double sugar medium by the various members of the colon typhoid group: ORGANISM SLANT BUTT B. Coli Acid Acid and gas B. Paratyphoid A No change c c c c c c B. " B I C Ct c c c c < < < ( (( (but decolorized if litmus is the indicator) B. typhosus C C Ct Acid, no gas B. dysenteriae C C C C c c c c c c If the reaction of the unknown organism on Russell's double sugar medium is indicative of typhoid, paratyphoid, or dysentery bacilli, agglutination tests should be carried out with stock sera. For this purpose macroscopic agglutinations are more satisfactory than microscopic. A series of dilutions of stock sera are made, ranging from 1:100 to 1:3200. Equal parts of diluted serum and saline suspension of the unknown organisms are mixed in agglu- tinating tubes and incubated at 3'7° C. for two hours, then put in ice box overnight. Caution.-In stating the degree of dilution of serum which causes agglutination it should be remembered that the ultimate dilution 265 ROUTINE BACTERIOLOGICAL AND SEROLOGICAL METHODS after addition of equal amount of saline suspension is to be re- ported. Thus if we have a tube containing 0.5 c.c. of a dilution of serum 1:600 and add to that tube 0.5 c.c. of a suspension of bacteria, the dilution of that serum must then necessarily be 1:1200. Only stock serum whose agglutinating titer has been determined previously should be used in testing the unknown culture. Agglutination reactions should always be checked up with sugar reactions using dextrose, lactose, saccharose and mannite. For table of differential sugar reactions see Hiss and Zinsser, Textbook of Bacteriology, p. 445. Urine.-Insist on having only catheterized specimens of urine for culture. In case typhoid fever is suspected the sediment ob- tained by centrifuging in sterile tube should be inoculated on Endo's media and handled in the same manner that stools are. (See above.) The sediment should also be inoculated on plain blood agar plates. Urine from a case of suspected tuberculosis should be inoculated into a guinea pig and the pig autopsied six weeks later, if in the meantime it has not died. At autopsy make smears from any sus- picious areas and stain for tubercle bacilli. If suspicious lesions are found, they should be cut out and sent to the Pathological Department for histological study. Always make a description of the inoculated pig so as to be able to identify the animal, as pigs frequently lose their ear tags. Exudates and Transudates.-Exudates and transudates should be inoculated upon the following media: Blood agar, Plain broth or glucose broth, Deep glucose agar tube melted, plus ascitic fluid, and tube heated to drive out air and then stop- pered with rubber stopper. The latter tube need not be used if the material is frank pus, or from a purulent focus. If anaerobic cultures are desired, the material should be inocu- lated into deep milk tubes, which have been previously heated to boiling and then cooled rapidly. After inoculation they are lay- 266 METHODS IN MEDICINE ered with sterile vaseline. The material should also be inoculated into anaerobic beef medium, treated in the same fashion as milk. Smears should be made of the pus and stained with Gram's stain. By so doing one may get hints as to whether or not any particular media should be used. Spinal Fluid.-Spinal fluid should be centrifuged and the sed- iment inoculated on: 1. Plain blood agar, 2. Brown blood agar, 3. Glucose broth. The meningococcus is susceptible to cold, hence spinal fluid should be inoculated as soon as possible after withdrawal from the body and in no case should it be placed in the ice box before inocu- lation. If plenty of fluid is available, it may be of advantage to incubate a tube of the fluid itself for twenty-four hours before culturing. Blood Cultures.-Blood cultures are to be made at the bedside. Inoculate two flasks of glucose broth with varying amounts of blood, say 1 c.c. and 5 c.e. Pour three plates, using about 2.0 c.c. of blood for each, one to be poured from plain agar and two from glucose agar. (Use deep tubes.) If the case is suspected typhoid fever, add 2 c.c. of blood to a flask containing glycerine peptone bile and 2 c.c. to a tube of milk. Daily transplants from each flask to glucose agar should be made for a period of seven days. It should be remembered that the percentage of positive results in any series of cases is in direct proportion to the number of cultures made. In cases of suspected endocarditis in which the blood cultures made with the ordinary technic have been negative, it is well to try Rosenow's method. This is as follows: Put 10 to 20 c.c. blood in a flask containing 50 to 100 c.c. of sterile distilled water and shake gently until the blood is laked. Centrifuge the laked blood in sterile centrifuge tubes at high speed and inoculate the sediment into melted deep glucose agar tubes. This method must be carried out with care to prevent contamination. It is particularly applicable in strepto- coccus infections. ROUTINE BACTERIOLOGICAL AND SEROLOGICAL METHODS 267 No blood culture is to be reported negative until the flasks and plates have been incubated for seven days. Points in differential diagnosis of pneumococci and streptococci: PNEUMOCOCCUS STREPTOCOCCUS Morphology Lance shaped diplococci, sometimes in short chains Round, tendency for chains. Broth Diffuse turbidity Sediment with clear super- natant fluid. Blood Agar Flat greenish colonies. No hemolysis. Small whitish colonies slightly elevated, some- times green by trans- mitted light, may be hemolysis. Inulin Acid and coagulation No change Normal Horse Serum No agglutination Agglutination Bile Soluble Insoluble Important.-None of the above points of difference is conclusive except that relating to bile solubility and no report of pneumococ- cus or streptococcus can be made that does not include such test. Note.-A colony of streptococcus hemolyticus will not show he- molysis in the presence of glucose, hence before reporting an or- ganism streptococcus viridans, be sure that it has produced no hemolysis on plain blood agar. ORGANISM BEST MEDIA FOR GROWTH B. diphtheriae Pneumococcus Streptococcus Staphylococcus B'. Influenzae Meningococcus B. Typhosus and allied organisms Gonococcus Loeffler's blood serum Whole blood agar Whole blood agar Any agar Whole rabbit blood agar Brown blood agar Whole blood agar Brown blood agar Hydrocele glucose agar Any agar Brown blood agar in which the agar has a reaction of pH 7.5 Chopped Beef 500 gm. Water 1000 c.c. Medium for Preserving Stock Cultures Place on a water-bath at 50° to 55° for one hour. Strain through cloth and restore volume.' Add Peptone 10 gm. NaCl 5 gm. Gelatin 300 gm. 268 METHODS IN MEDICINE Dissolve, filter, adjust to 1 per cent acid, hydrogen-ion concen- tration. Sterilize 20 minutes at 100° C. Inoculate. Place cultures at 37° C. for 24 hours, then store at 20° C., except meningococcus and gonococcus, which require 37° C. B. coli remains unchanged for eleven months. B. typhosus remains unchanged for eight months. B. paratyphosus remains unchanged for eight months. Meningococcus remains unchanged for eight months. B. pertussis remains unchanged for eight months. B. dysenteriae remains unchanged for eight months. Streptococcus remains unchanged for four months. Method for the Demonstration of Spirochetae Pallidae Warthin and Starry's Silver-Agar Cover-Glass Method.-1. Fixation should be begun as soon as possible and be complete to give the best results. Thin slices of tissue, from 5 to 7 mm. thick, left in 4 per cent neutral formaldehyde (10 per cent formaldehyde solution) from one to three days, give the best results. 2. If the formaldehyde fixation is complete, it is not necessary to wash the tissue in water before putting it into 96 per cent alcohol. From 96 per cent alcohol the tissue is run through absolute al- cohol, two changes of xylene and two of 52° C. paraffin. 3. The sections should be cut about 5 microns thick for the best results, although from 8 to 12 microns give practical sections. As they are cut, they are floated on warm distilled water which has recently been boiled to drive off the air. The under or shiny side of the section is placed on the water. When the sections have flat- tened out on the warm water, they are caught up on the prepared cover-glasses, the water blotted off, and then dried over the flame or in the drying oven. The cover-glasses should be No. 1 or thin No. 2, three-quarter inch squares, or larger if the size of the sec- tion requires. They must be perfectly clean, free of all dirt and grease. A minimum amount of albumin fixation should be spread evenly on the clean cover-glass, so that there will not be enough of it to become heavily stained. The prepared cover-glasses should ROUTINE BACTERIOLOGICAL AND SEROLOGICAL METHODS 269 be placed on a clean card-board, covered with clean paper and dried in the incubator for twelve hours before using. They should not be dried by passing through the flame. It is advisable, there- fore, to keep a supply of such prepared cover-glasses on hand. 4. After the mounted paraffin sections have been dried on the cover-glasses, the paraffin is removed by heating over the flame, dropped into xylene, then placed in absolute alcohol and finally rinsed in distilled water. 5. The silver impregnation should be carried out in the dark (dark bottles covered with black paper). Wide-mouthed bottles with tightly fitting corks should be used. The mounted cover-glass is taken from the distilled water, rinsed in 2 per cent silver nitrate solution and then covered with another clean cover-glass also wet with the silver solution. The silver solution should always be freshly made, and should never be used after it is from three to four days old. During this time the same solution may be used over and over again, if kept uncontaminated and in the dark bot- tle. The bottle should contain enough of the silver solution so that when the cover-glasses are placed on edge against the side of the bottle, it will not completely cover them. The cover-glasses are held together by capillary attraction, and if placed against the side of the bottle wet and the silver solution then poured in so as not to cover them completely, they will be held upright also by capillary attraction, and will not slip apart. The bottle is then tightly corked and placed in the incubator for from thirty minutes to one hour. After impregnation, the cover-glasses are removed, separated, and the mounted section put into the reducing mixture section side up. 6. The reducing mixture consists of 3 c.c. of a 2 per cent silver nitrate solution, 5 c.c. of warm glycerin, 5 c.c. of a warm 10 per cent gelatin solution, and 5 c.c. of a 1.5 per cent warm agar sus- pension, to which mixture from 0.25 to 2 c.c. of a 5 per cent hydro- quinone solution is added just before using. The warm glycerin and gelatin solutions and the silver nitrate are first thoroughly mixed, then the agar suspension is stirred in with a glass rod, and finally the hydroquinone, just before the sections are placed in the mixture. The agar suspension must be carefully made. One and five-tenths gm. of agar cut up into small bits is added to 100 c.c. of distilled water and carefully and slowly heated to the boiling point, 270 METHODS IN MEDICINE being constantly stirred with a glass rod. When the agar has gone into fine suspension, the solution is poured into a bottle, which is corked tightly and kept on top of the paraffin oven. Should the agar become flaky and settle out, it must be brought to the boiling point again, with constant stirring. It should be just thin enough to pour, and not too thin and watery. If it remains too thin, al- low the agar to cool until it sets, then shake until thoroughly broken and place on the oven. The glycerin and gelatin solutions can also be kept warm on top the paraffin oven. The amount of hydroquinone added to the reducing mixture varies somewhat with the tissue and the fixation. In general it is best to use as small an amount as possible so that the reduction is not too rapid. A slow reduction usually gives the best results; but if too slow, precipitates will form and the spirochetes will not be well stained. Usually from 0.5 to 1 c.c. gives the best results; but in some cases more may be required. After the hydroquinone has been added, the mixture is stirred vigorously for a short time. It is then poured into a staining dish, and the mounted section re- moved from the silver solution, the cover-glasses separated, and that holding the section immersed in the reducing mixture for a number of seconds until reduction is complete. The longer the section is in the reducing mixture, the darker it will be. 7. When it becomes a light reddish brown, it is removed and washed in a 5 per cent sodium thiosulphate solution, then rinsed in distilled water, dehydrated in absolute alcohol, cleared in pure xylene, and mounted in balsam. When the sections have been properly stained they will be light reddish brown. If a deep brown or black, the tissue will be too deeply stained and the spirochetes not sufficiently contrasted. Usu- ally the albumin fixative on the cover-glass about the section is stained somewhat, and this can be rubbed off with a clean cloth, care being taken not to touch the section with the cloth. The upper surface of the cover-glass should be similarly cleaned. The section, of course, must never be allowed to get dry after the paraffin has been removed. Smears from suspicious lesions may be stained according to this same technic. ROUTINE BACTERIOLOGICAL AND SEROLOGICAL METHODS 271 Latest Modification in the Technic (Warthin and Starry, Personal Communication) More constant and better results can be obtained if the sections, before they are placed in the silver nitrate, are placed in a 3 per cent hydrogen peroxide solution for five to thirty minutes. They are then washed thoroughly in two changes of distilled water and placed in the silver nitrate solution in the usual way. A pure hy- drogen peroxide solution prepared of barium chloride, etc., put up in a slightly acidulated solution, should be used. This reagent as described is prepared by Parke, Davis & Co., Detroit. Reference: Warthin, A. S., and Starry, A. C.: Jour. Am. Med. Assn., Jan. 22, 1921, Ixxvi, 234. COMPLEMENT-FIXATION TECHNIC The Wassermann and other complement-fixation reactions arc done as follows: I. Preparation of Reagents.-(a) Amboceptor animals are im- munized with sheep red cell suspension (about 20 per cent in nor- mal salt solution) in ascending amounts as 1 c.c., 2 c.c., 5 c.c. at four-day intervals. Care is taken to give the second and subse- quent injections very slowly and in divided doses in order to avoid death of the animal. Two days after the last injection the animal is bled, the serum is titrated and, if satisfactory, is pre- served in sterile sealed tubes containing about 1 c.c. of serum. (b) Complement.-Usually it is necessary to draw 6 or 7 c.c. from 6 to 8 guinea pigs by heart puncture for each day's work. These are allowed to clot at 37° for 15 minutes and then centrifuged. (c) Sheep Corpuscles.-Sheep cells are washed in normal salt solution by centrifuging twice for five minutes and finally for fifteen minutes. A 5 per cent suspension is then made of the sedi- ment in normal salt solution. (d) Hemolytic System.-Titration is arranged so that both com- plement and amboceptor are titrated as illustrated in the following tables: Complement 1:10 0.4 0.3 0.25 0.2 0.1 Amboceptor, as titrated 0.25 0.25 0.25 0.25 0.25 Cells 0.5 Normal salt solution 1.25 - - - - 272 METHODS IN MEDICINE Complement 1:10 0.25 0.25 0.25 0.25 0.25 Amboceptor, as titrated 0.4 0.3 0.25 0.2 0.1 Cells, 5 per cent 0.5 - - - - Normal salt solution 1.25 - - - - Incubation in water-bath at 37° C. for thirty minutes. Four tubes in each row must show complete hemolysis. The comple- ment is sometimes further diluted to 1:11 or 1:12, if the titration so indicates, but is never used in a dilution lower than 1:10. In the test 0.5 c.c. of complement, amboceptor and of sheep cells are used. (e) Antigen.-Ordinary alcoholic and cholesterin antigens pre- pared in the usual way are used. These antigens are titrated in the presence of strongly positive serums. Previously the antigenic dose was governed by the capacity for fixation, but more recently it has been the custom to titrate antigen for its anticomplementary value and to use % of this amount in the test, provided, of course, that the antigen is effective in fixing known positive serums in a dose smaller than that used in the test. II. Test.-(a) One-tenth c.c. inactivated patient's serum is im- mersed for one hour in water-bath at 37° C., in the presence of 0.5 c.c. of complement and 0.5 c.c. of antigen properly diluted, and enough salt solution to make a total quantity of 1.5 c.c., all thoroughly mixed by shaking. An anticomplementary control consists of 0.2 c.c. of patient's serum with 0.5 c.c. of complement and salt solution enough to make 1.5 c.c. About ten minutes before the end of the hour, equal quantities of amboceptor, properly diluted, and 5 per cent sheep red cells suspension are quickly mixed and allowed to stand at room temperature until ready for use. Then 1 c.c. of these sen- sitized cells is added to each tube and thoroughly mixed by shak- ing. Incubation in water-bath is then continued for fifteen min- utes, unless the anticomplementary serum control fails to clear, and is placed in the ice box overnight. Every day the tests are read, the results are compared with clinical data and criticism of the accuracy of the test is based on the agreement of the result with the clinical diagnosis. (b) For the tubercle bacillus fixation, the hemolytic system is titrated as above. The antigen is made from the tubercle bacillus, ROUTINE BACTERIOLOGICAL AND SEROLOGICAL METHODS 273 grown on Petrofl:'s medium, dried and ground for a period of from three to four hours, then suspended in saline. The antigen is then titrated for its anticomplementary and antigenic qualities with a known positive serum. Tn the test .25 c.c. of complement are used. (c) For the gonococcus fixation. The antigen is made from the gonococcus grown on Thalman's agar, and suspended in normal saline, of preferably pn 8.0. The antigen is then inactivated for 30 minutes at 56° C., and titrated against a known positive serum for its antigenic and anticomplementary qualities. The antigen very quickly becomes A.C., so that it is found advisable to pre- pare a fresh antigen whenever a new test is run. Twenty-hun- dredths c.c. of complement are used. Interpretation of the Wassermann Reaction with non- cholesterinized an- tigen Reaction with cho- lesterinized antigen Interpretation Syphilis No serological evi- dence of active syph- ilis. It should always be borne in mind that the Wassermann reaction is a nonspecific reaction. It has great diagnostic value, but it is not necessarily the final word in all cases and care is needed in the interpretation of results. It is essential that the laboratory receive the clinical diagnosis of the case in each instance. There is room provided for this in- formation on each Wassermann request slip. It is only by check- ing up the information gained in this manner that a true inter- pretation of the value of the reaction can be obtained. Unless the information is supplied with each specimen the laboratory will be constrained to refuse to carry out the tests on such specimens. After the blood is withdrawn and placed in the collecting tube the latter should be slanted, not left standing upright. This procedure facilitates the separation of serum from clot and aids the laboratory work. The cooperation of all departments in this matter is earnestly requested. In the case of a ++ reaction with the cholesterinized antigen 274 METHODS IN MEDICINE the decision as to whether or not the patient has or has had active syphilis will depend upon the clinical history of the case. If there is reasonably definite history of syphilitic infection, or it is certain that the patient has had antisyphilitic treatment, or if there is clinical evidence of syphilis, a ++ reaction with the cholesterin antigen is very significant and its importance increased under such conditions. On the other hand, in the absence of these factors, a ++ reaction with this antigen is not considered to be necessarily an indication of the presence of syphilis and such a reaction of itself should not be made the basis for instituting treatment. Such reactions are not uncommon in patients who have been treated actively for syphilis; however, a + reaction with the cholesterin antigen is of very slight significance from a diag- nostic standpoint although it may be useful in following treatment. Such a reaction is not to be considered as indicating the presence of syphilis except where there is abundant clinical evidence of this disease. Indeed a serum yielding a + result will, when the test is repeated, frequently yield a negative result. Patients whose sera yield a + or ++ result should have a second test performed if this result conflicts in any way with the clinical diagnosis. The noncholestcrinized alcoholic extracts of heart muscle yield less sensitive antigens than the cholesterinized extracts. Conse- quently when reactions performed with these antigens yield posi- tive results, even if the amount of fixation is slight, the fact is highly significant. Even + results with such antigens are important and point to the presence of syphilis, while reactions yielding ++, + + +, and + + + + results are almost pathognomonic of syphilis. As a rule it will be found that where the noncholesterinized antigens yield + and ++ reactions the cholesterinized ones yield + + + and + + + + re- sults. Occasionally sera will be found that yield a + + + + result with the cholesterinized antigen and a negative reaction with the noncholesterinized antigen. In the light of experience with the more sensitive antigens such sera should be regarded as syphilitic unless there is the strongest reason for excluding syphilis on clin- ical grounds. Briefly the interpretation of the Wassermann reaction may be represented in the accompanying table. ROUTINE BACTERIOLOGICAL AND SEROLOGICAL METHODS 275 REACTION WITH NON- CHOLESTERINIZED ANTIGEN REACTION WITH CHOLESTERINIZED ANTIGEN INTERPRETATION 4444- 4444- Syphilis +++ 44-44- cc 44- 44+4- C c + 4+H- C c - 4+H- Very probably syphilis 4-4- -| 4~4~ CC CC CC + 444- C C C C Ct - -H-4- C C Ct c c + 44- Strongly suspicious of syphilis - 44- Suspicious of syphilis, but should be con- firmed by clinical evidence + 4- Idem. - 4- Only slightly suspicious of syphilis, and of no significance in the absence of history or clinical evidence Ice Box Fixation Test When the period of primary incubation is extended to four hours and incubation carried out at ice box temperatures, some revisions in interpretation are necessary. This procedure will un- doubtedly increase the number of positive reactions to the Was- sermann test. All cases that give completely negative reactions with this method with both antigens will be reported at once. Any case giving any degree of positive reaction will be repeated on the following day, using the former method of performing the test, namely, primary incubation for one hour at 37° C. In these cases the results of the tests by different methods on the same serum will be reported on the slip thus: FIXATION FOR FOUR HRS. IN THE ICE BOX FIXATION FOR ONE HR. IN THE INCUBATOR Result: Cholesterin antigen, 4 plus. 4 plus. Noncholesterin antigen 4 plus. 2 plus. Interpretation.-Clinicians should remember that the "ice box method" of performing Wassermann tests is a very delicate one and necessitates care in interpreting the results. Particularly is this true of the cholesterinized antigen which is exceedingly deli- cate antigen. If the test is negative with both antigens by the ice box method, it is safe to assume that the patient has not active 276 METHODS IN MEDICINE syphilis. The status of the weakly positive reactions with the cholesterinized antigens has not as yet been finally determined, particularly as carried out with the ice box method, hence we advise that until more is known about this phase of the reaction, little attention be paid to weakly positive reactions, (2 plus, 1 plus) with the cholesterinized antigen alone. If the noncholes- terinized antigens yield positive reactions, even of slight degree, they should be given serious consideration. Experience has shown that the alcoholic antigen in this climate does not give slight or partial reactions with any considerable portion of sera from per- sons free from syphilis. Cholesterinized antigens, on the contrary, have been observed to give slight or partial reactions with 10 per cent or less of sera from persons apparently free from syphilis, depending upon how sensitively the test is adjusted. PART III DIETETIC METHODS CHAPTER XIX GENERAL WARD DIETS, DIETS IN INFECTIOUS DISEASE, HIGH AND LOW CALORIC DIETS All foods, unless otherwise ordered, are to be weighed cooked. Bread, each slice to average 30 gm. Toast, each slice to average 20 gm. Each glass of liquid served to average 250 c.c. When special diets are ordered, the routine feedings at 10 a.m., 3 p.m. and 8 p.m. are to be omitted. All milk should be "whole milk." Cream should average 20 per cent. On diet list weights and measures are to be in black; calories in red. Liquid Diet 1800 Calories Weights in Grams SERVING TIME FOOD GRAMS PROT. FAT CARBOHY. CALORIES 8 A.M. Oat Meal gruel Oat Meal 20 3.2 1.4 13.3 Cream 100 ■ 2.5 20 4.5 Cocoa 5 1.0 1.4 1.8 Milk 100 3.3 4.0 5.0 Sugar (15) per 50 day 50.0 10 A.M. Orange Albumin Orange juice 100 .8 .2 11.6 Egg White Sugar (10) 25 3.1 .0 12 M. Chicken Consomme Ice Cream 200 4.4 Egg (1) 50 6.7 5.2 4.5 Cream Sugar (10) Vanilla 100 2.5 20 2 P.M. Grape Juice 100 1.3 1.6 14.9 277 278 METHODS IN MEDICINE Liquid Diet 1800 Calories-Cont'd Weights in Grams SERVING TIME PROT. FAT CARBOHY. CALORIES FOOD GRAMS 4 P.M. Egg nog Egg (1) 50 6.7 5.2 Cream 100 2.5 20 4.5 Milk 100 3.3 4.0 5.0 Sugar (5) Flavoring 6 P.M. Pea Puree Peas 100 3.6 2 8.6 Cream 50 1.2 10 2.2 Milk 300 6.6 8.0 10.0 8 P.M. Cocoa 5 1.0 1.4 1.8 Whipped Cream 50 1.2 10 2.2 Milk Sugar (10) 150 4.0 6.0 7.0 59.8 111.4 142.4 1811.4 Liquid Diet Feedings every two hours from 6 a.m. to 8 p.m. and as nearly every two hours as possible when patient wakes during the night. Whole milk Buttermilk Ice Cream Cocoa Coffee Tea Strained soup Fruit juice with water Albumin water Meat juice Gruels of cereals Water Gelatin Serve 250 c.c. at each feeding. Soft Diet Three meals daily at 7 a.m., 12 n. and 5 p.m. At 10 a.m., 3 p.m. and 8 p.m. serve one article from liquid diet list. Anything on liquid diet list may be served at meal time. Patients shall not be allowed any food brought in by visitors without special permission. 279 GENERAL WARD DIETS Butter Cheese, cottage or neufchatel (American cream, if finely grated) Eggs, according to taste (raw, soft-boiled, or poached) Potatoes (white, well cooked, baked, boiled, creamed, scalloped, with or without grated American cream cheese) Bread (white only), toast (do not remove crusts) Crackers, graham or soda Apple sauce or baked apple (without skin). Other stewed fruits, as apricots, peaches, prunes and canned fruits, stewed until falling to pieces or run through strainer. Cream toast Cereals: Flakes Gruels Mush Oatmeal Rice Macaroni Shredded wheat biscuit Puddings: Bread Rice (made with raisins, if so desired) Chocolate Meal Custard Tapioca Spanish cream Ices or ice cream Gelatin Three meals daily, at 7 a.m., 12 noon and 5 p.m. At 10 a.m., 3 p.m. and 8 p.m. any one article from liquid diet list. Anything on liquid or soft diet list may be served at meal time. Light Diet 280 METHODS IN MEDICINE Patients should not be allowed any food, except fruit, brought by visitors unless special permission has been granted. Meat: (small amount, once daily); Beef roast Steak Stew Veal or mutton chops Liver Kidney Poultry Scraped beef Fish: (no shell fish) Vegetables: (well cooked) Asparagus Squash Beans Tomatoes Carrots Turnips Celery Beets Corn Onions Peas Parsnips Spinach White and sweet potatoes, well cooked, (baked, boiled or creamed) Fruit: (fresh or canned) Apples Lemons Bananas (ripe) Oranges Blackberries Peaches Grape Fruit Raspberries Grapes Strawberries Cherries Watermelon Fruit: (dried or stewed) Apricots Raisins Prunes Apples Figs Rhubarb Bread: Brown, buns, graham, corn, rolls, white, zwieback. Crackers: soda or graham. Cream toast Hominy Cake GENERAL WARD DIETS 281 Regular Diet Three meals daily, 7 a.m., 12 n., and 5 p.m. At 10 a.m., 3 p.m. and 8 p.m. any one article from liquid list. Anything on light, soft or liquid diet may be served at meal time. Food brought to patients by visitors shall be turned over to nurses, who shall see that it conforms to regular diet. Meat: (average helping once or twice daily in addition to light diet). Lamb or mutton Vegetables: Poultry Beets Meat pie with pastry crust Parsnips Fish, including oysters, crabs, clams. Squash Fruit: Fresh, cooked or canned. Tomatoes Bread: Plenty. Not hot and fresh. May have nuts, candy, and condiments. Pastry: Apple or apricot cobbler. Moderately High Caloric Diet WEIGHTS IN GRAMS FOOD 8 A.M. 12 M. 6 P.M. ORDER PROT. 100 7 FAT 5-100 CARBOHY. 500 CALORIES Prunes 100 for whole 100 2.1 73.3 Cornflakes 25 day 25 1.3 3 20.2 Sugar 71 71 71 Egg 50 50 6.7 5.2 Ham 100 100 16.3 38.8 Cream 50 50 1.2 10 2.5 Bread 50 50 50 150 12.4 1.9 78.9 Butter 10 10 10 30 .3 25.5 Potato 150 150 3.3 .1 27 Pears (c) 100 100 .3 .3 18 Peas (c) 100 100 3.6 .2 8.6 Beets 100 100 1.6 .1 8.6 Steak 75 75 14.7 9.5 Flour for steak 10 10 20 2.2 14.8 and chicken Tapioca 15 15 13.2 Sweet potatoes 150 150 4.7 1 39.1 Pineapple 100 100 .4 .7 36.4 Lima beans 100 100 .4 .3 13.4 Chicken 100 100 21.5 2.5 Honey 50 50 .2 40.6 Raisins 50 50 1.3 1.6 38 Lemon Juice 50 50 4.9 Consomme 200 200 4.4 100.6 98.1 502.2 3292.9 282 METHODS IN MEDICINE 6 :30 A.M. Hot milk 250 c.c. 160 7 A.M. Cooked cereal 100 gms. 60 Cream 50 c.c. Sugar 25 gms. 200 Eggs, 2 soft boiled 160 Toast 40 gms. 120 Butter 20 gms. 160 Milk or coffee 250 c.c. 160 10 A.M. Milk or Cocoa Malted milk with 250 c.c. 160 Crackers, 2 soda 20 12 N. Soup 250 c.c. 100 Meat (roast, stewed, steak or fowl) 100 gms. 200 Bread 100 gms. 200 Butter 20 gms. 160 Potato or rice 50 gms. 60 Green vegetables 50 gms. 25 Apple sauce 25 gms. 30 Jelly, Junket, Pudding Custard or ice cream 100 gms. 150 Milk 250 c.c. 160 3 P.M. Milk or Malted milk with 250 c.c. Egg, 1 300 5 P.M. Soup 250 c.c. 100 Egg, 1 soft boiled 80 Chop or cold meat 50 gms. 100 Bread 100 gms. 200 Butter 20 gms. 160 Baked apple or stewed fruit 50 gms. 100 9 P.M. Hot milk with 250 c.c. Eggs, 2 raw 320 ' 3640 If patient wakes through night give hot milk, 250 c.c Water with meals and ad lib. throughout the day. Convalescent Tuberculosis Diet DIETS IN INFECTIOUS DISEASES 283 TYPHOID DIETS Typhoid diets should not be ordered, with "typhoid routine," on admission of a suspected case, but only after a few days' observa- tion of patient's digestion (appetite, abdominal distention, and stool) on low diet (e.g., liquid diet) or water only. 6 a.m.-Egg malted milk (large glass) various flavorings-300 cal. 1 tablespoonful fresh malted milk 4 tablespoonfuls cream or 2 tablespoonfuls cream and 2 tablespoonfuls sugar, one egg and % glass milk. 8 a.m.-Strained cereal, rice, oatmeal (fine), cream of wheat with cream and sugar. 3' oz. cereal 100 cal. 4 tablespoonfuls cream and 200 " 2' tablespoonfuls sugar, and one egg 80 " 1 poached egg (soft) 75 " Egg chocolate or one cup of cocoa 270 cal. 1 heaping teaspoonful cocoa 1 heaping teaspoonful sugar % cup milk 1 teaspoonful cream. 9 a.m.-Egg lemonade with white of egg, -190 cal. or glass of milk 150 cal. 10 a.m.-Eggnog (290 cal.) or milk gruel, strained (100 cal.) 12 m.-1 slice buttered toast 75 cal. 1 poached egg 75 " Coffee, cream, sugar 75 " Ice cream or custard 200 " 2 p.m.-Egg chocolate or eggnog, gruel or broth-290 cal. 3 p.m.-Buttermilk 80 cal. Hot or cold milk 150 " or milk gruel 100 cal. 4 p.m.-Ice cream (200 cal.) junket (150 cal.) or custard (200 cal.) 6 p.m.-Cream toast 325 cal. 1 or 2 poached eggs 75 " Cocoa or 270 " Tea with cream and sugar 150 " 8 p.m.-Gruel 100 cal. Hot or cold milk or 150 " Malted milk 220 " 9 p.m.-Buttermilk 80 cal. Approximately 3500 calories. 284 METHODS IN MEDICINE Coleman-Shaffer Dietetic Management of Typhoid Fever High Calory Typhoid Diets Directions for Nurses.-High caloric diet does not indicate the administration of a previously calculated number of calories. The caloric value is to be calculated at the end of each day. There must be individualization of feeding. Each patient, not the dis- ease, must be fed. Patients should be told the more they eat, the sooner they will get well, and to ask the nurse for more food if they desire it. Each patient is to have as much food as he is capable of digesting. Note if there are any articles of food in the diet that the patient will not take or wishes changed. In such a case, substitute articles of diet may be chosen from the approved list, if in accordance with the doctor's orders. Eggs should be raw, coddled, or soft boiled, never hard. They may be used in eggnogs, custards, omelets, or scrambled. All toast should be prepared with crusts removed. Unless otherwise specified, milk and cream means whole milk and 20 per cent cream. Twenty per cent cream is about the same as the top 4 ounces (120 c.c.) from a quart (1000 c.c.) bottle of milk that has stood at least six hours. To add lactose to milk, boil 15 grams (% ounce) in 30 c.c. (1 ounce) of water for 2 minutes, dissolve completely, cool and add to the milk. To combine lactose, egg and coffee or tea: Beat the egg lightly in a cup; dissolve lactose thoroughly in very hot coffee or tea; pour on to the beaten egg stirring while pouring, strain, add sugar and cream if desired and serve hot or cold. To make egg lemon-juice mixture: Dissolve sugar in water; add lemon-juice and pour on to beaten egg and add cracked ice, or mix ingredients in a shaker and shake up thoroughly, strain and serve. If lactose is to be added, it is boiled with the sugar water for two minutes and cooled before adding lemon-juice. High caloric typhoid diets 285 All food is to be stopped immediately upon the appearance of any signs of hemorrhage. With vomiting, all food is to be withheld for a few hours, and then the diet reduced to its simplest form, avoiding all rich mix- tures. If tympanites is troublesome, the excess of lactose must be removed, secondly the eggs eliminated, then the cream and lastly the total caloric intake reduced to 1500 or 1000 calories. Alcohol may be taken with advantage in the form of whiskey (200 cal. per 30 e.c.) by patients who persistently decline all food. Or it can be used to increase the caloric intake on the low diets. As much as 60 c.c. may be used every three hours. Table of Approximate Values of Ingredients Used in High Caloric Diets FOOD AMOUNT i CALORIES Apple sauce without sugar 1 ounce (30 c.c.) 30 Apple, pared and cored 1 medium, about 75 Bread average slice 30 grams 80 Butter, one pat 13 grams, about 100 Cocoa, one rounding teaspoonful 5 grams 25 Crackers, soda, one cracker 9 grams 36 Crackers, Uneeda, one cracker 6 grams 25 Cream, (20 per cent) 1 ounce (30 c.c.) 60 Egg 1 average size 75 Egg white White of 1 egg 15 Egg yolk Yolk of 1 egg 60 Farina (cooked) 1 heaping tablespoonful 25-30 Lactose (milk-sugar) 1 heaping teaspoonful 40 Lactose (milk-sugar) 1 measured ounce, 18 gr ams 72 Lemon-juice 1 ounce (30 c.c.) 12 Milk (whole) 1 ounce (30 c.c.) 20 Orange 1 large 100 Orange-juice 1 ounce (30 c.c.) 15 Oatmeal (rolled oats, cooked) 1 heaping tablespoonful 36 Potato 1 medium 100 Rice, (boiled) 1 heaping tablespoonfu], about 60 Sugar, cane 1 heaping teaspoonful 40 Sugar, cane 1 level tablespoonful 56 Toast average slice 80 286 METHODS IN MEDICINE High Caloric Typhoid Diets Menus Arranged by Miss Mary E. Sheehan and Miss Estelle Magill for Dr. Warren Coleman CALORIES I. For 1000 calories a day A. Milk, 1 quart (1000 c.c.) 700 Cream, 1% ounces (50 c.c.) 100 Lactose, 1% ounces (50 grams) 200 This furnishes eight feedings, each containing: Milk, 4 ounces (120 c.c.) 80 Cream, 2 drams (8 c.c.) 15 Lactose, 1% drams (6 grams) 24 Or B. Eggs, 2 150 Lactose, 30 grams (1 ounce) 120 Sugar, 25 grams (% ounce) 100 Milk, 800 c.c. (26 % ounces) 560 Cream, 30 c.c. (1 ounce) 60 Lemon juice, 30 c.c. (1 ounce) 12 Coffee, 150 c.c. (5 ounces) 00 Tea, 150 c.c. (5 ounces) 00 This furnishes seven feedings, One feeding containing: Coffee, 150 c.c. (5 ounces) 00 Egg, 1 75 Lactose, 30 grams (1 ounce) 120 Sugar, 5 grams (1% drams) 20 1. One feeding containing: 2. Tea, 150 c.c. (5 ounces) 00 Cream, 30 c.c. (1 ounce) 60 Sugar, 5 grams (1% drams) 20 Four feedings, each containing: 3. 4. 5. 6. 'Milk, 200 c.c. (6% ounces) 140 One feeding containing: Egg, 1 75 Sugar, 15 grams (% ounce) 60 Lemon juice, 30 c.c. (1 ounce) 12 Water, 120 c.c.-150 c.c. (4 or 5 ounces) 00 7c 287 HIGH CALORIC TYPHOID DIETS CALORIES II. For 1500 calories a day: A. Milk, 1% quarts, (1500 c.c.) 1000 Cream, 1% ounces (50 c.c.) 100 Lactose, 3% ounces (100 grams) 400 This furnishes six feedings, each containing: Milk, 8 ounces (240 c.c.) 160 Cream, 2 drams (8 c.c.) 15 Lactose, % ounce (16 grams) 64 Or B. Eggs, 2 150 Lactose, 110 grams (3% ounces) 440 Sugar, 25 grams (% ounce) 100 Milk, 800 c.c. (26% ounces) 560 Cream, 120 c.c. (4 ounces) 240 Lemon juice, 30 c.c. (1 ounce) 00 Coffee, 150 c.c. (5 ounces) 00 Tea, 150 c.c. (5 ounces) 00 This furnishes one feeding containing: 1. Coffee, 150 c.c. (5 ounces) 00 Egg, 1 75 Lactose, 40 grams (1% ounces ) 160 Sugar, 5 grams (% ounce) 20 One feeding containing: Tea, 150 c.c. (5 ounces) 00 Cream, 50 c.c. (1% ounces) 100 Lactose, 30 grams (1 ounce) 120 Sugar, 5 grams (% ounce) 20 2.- Four feedings, each containing: 3. 4. 5. 6. Milk, 200 c.c. (6% ounces) 140 Cream, 17 c.c., large tablespoonful (% ounce) 34 One feeding containing: Egg, 1 75 Lactose, 40 grams (1% ounces) 160 Sugar, 35 grams (% ounce) 60 Lemon juice, 30 c.c. (1 ounce) 12 .Water, 120-150 c.c. (4 or 5 ounces) 7/ 288 METHODS IN MEDICINE CALORIES III. For 2000 calories a day: A. Milk, iy2 quarts (1500 c.c.) 1000 Cream, 8 ounces (240 c.c.) 500 Lactose, 4 ounces (120 gm.) 500 This furnishes seven feedings, each containing: Milk, 7 ounces (210 c.c.) 140 Cream, 1 ounce (30 c.c.) 60 Lactose, 41z4 drams (18 grams) 72 Or B. Eggs, 2 150 Lactose, 125 grams, (4 ounces) 500 Sugar, 15 grams (% ounce) 60 Milk, 1000 c.c. (32 ounces) 700 Cream, 240 c.c. (8 ounces) 480 Cocoa, 5 grams (% ounce) 25 Orange juice, 60 c.c. (2 ounces) 30 Lemon juice negligible 00 Coffee, 150 c.c. (5 ounces) 00 This furnishes one feeding containing: Coffee, 150 c.c. (5 ounces) 00 Egg, 1 75 Lactose, 50 grams (1% ounces) 200 Sugar, 5 grams (% ounce) 20 1. One feeding containing: •Cocoa, 5 grams (% ounce) 25 Milk, 120 c.c. (4 ounces) 80 Cream, 60 c.c. (2 ounces) 120 Lactose, 50 grams (1% ounces) 200 2. One feeding containing: Egg, 1 75 Lactose, 40 grams (1% ounces) 160 Sugar, 10 grams (% ounce) 40 Orange juice, 120 c.c. (4 ounces) 60 Lemon juice, 4 to 8 c.c., 1 to 2 teaspoonfuls, (1 to 2 drams) 3. Four feedings containing: 4. 5. 6. 7. Milk, 210 c.c. (7 ounces) 140 Cream, 45 c.c. (1% ounces) 90 289 HIGH CALORIC' TYPHOID DIETS IV. CALORIES A. For 2500 calories a day: Milk, iy2 quarts (1500 c.c.) 1000 Cream, 8 ounces (240 c.c.) 500 Lactose, 8 ounces (240 grams) 1000 This furnishes seven feedings, each containing: Milk, 7 ounces (210 c.c.) 140 Cream, 1 ounce (30 c.c.) 60 .Lactose, 9 drams (36 grams) 144 Or B. Milk, 1000 c.c. (1 quart) 700 Cream, 240 c.c. (8 ounces) 480 Eggs, 3' 225 Lactose, 165 grams (5% ounces) 660 Sugar, 40 grams (iy3 ounces) 160 Bread, 1 slice, 30 grams (1 ounce) 80 Uneeda biscuit, 1 25 Butter, 10 grams (y3 ounce) 80 Orange juice, 120 c.c. (4 ounces) 60 Lemon juice (1% ounces) 20 This furnishes one feed'ng containing: Coffee, 150 c.c. (5 ounces) 00 Egg, 1 75 Lactose, 40 grams (1% ounces) 160 Sugar, 5 grams (% ounce) 20 Toast, 1 slice 80 Butter, 10 grams (% ounce) 80 1. One feeding containing: Egg, 1 75 Lactose, 50 grams (1% ounces) 200 Orange .juice, 120 c.c. (4 ounces) 60 Sugar, 10 grams (% ounce) 40 Lemon juice to taste. Water. 2/ One feeding containing: Egg, 1 75 Milk, 200 c.c. (6% ounces) 140 Cream, 40 c.c. (V/3 ounces) 80 Lactose, 25 grams (% ounce) 100 Sugar, 5 grams (% ounce) 20 Flavor with vanilla or nutmeg. 3/ 290 METHODS IN MEDICINE One feeding containing: calories 4. Lactose, 60 grams (2 ounces) 240 Sugar, 20 grams (% ounce) 60 Lemon juice, 30 or 40 c.c. (1 or 1% ounces) 15 Four feedings, each containing: 5/ 6. 7. 8-> Milk, 200 c.c. (6% ounces) 140 Cream, 50 c.c. (1% ounces) 100 V. A. For 3000 calories a day: Milk, iy2 quarts (1500 c.c.) 1000 Cream, 1 pint (480 c.c.) 1000 Lactose, 8 ounces (240 c.c.) 1000 This furnishes eight feedings, each containing: Milk, 6 ounces (180 c.c.) 120 Cream, 2 ounces (60 c.c.) 120 Lactose, 1 ounce (3'0 grams) 120 Or, B. Breakfast: 1. Farina 100 Toast, 1 slice (30 grams before toasting) 80 Cream, 100 c.c.*(3% ounces) 200 Butter, 8 grams (2 drams) 60 Lactose, 40 grams (1% ounces) 160 Sugar, 20 grams (% ounce) 80 Coffee, 1 large cup or 2 small cups (300 c.c.) 00 2. 10-10:30 a.m.: Milk, 200 c.c. (6% ounces) 140 Cream, 50 c.c. (1% ounces) 100 3. Dinner: Eggs, 2 150 Potato, 1 medium, about 100 Bread, 1 slice, or roll, 1, about 80 Butter, 30 grams (1 ounce) 234 Apple, 1 medium (pared and cored) 75 Sugar, 15 grams (% ounce) 60 HIGH CALORIC TYPHOID DIETS 291 4. 3 to 4 p.m. : CALORIES Tea, 150-200 c.c. (5 to 7 ounces) 00 Lactose, 50 grams (1% ounces) 200 Sugar, 5 grams (% ounce) 20 Cream, 50 c.c. (1% ounces) 100 Crackers, 3 LTneeda, or 2' soda, toasted 75 Butter, 8 grams (2 drams) 62 5. Supper: Rice, 25 grams (7 drams) or farina, cooked with 100 Milk, 300 c.c. (3% ounces) 70 Toast, 30 grams (1 slice) 80 Butter, 8 grams (2 drams) 62 Sugar, 5 grams (for cereal) (% ounce) 20 Cream, 60 c.c. (2 ounces) 120 Orange, 1 slice 100 Sugar, 5 grams (with orange) (% ounce) 20 6. 8 to 9 p.m. : Cocoa, 5 grams (% ounce) 25 Sugar, 10 grams (% ounce) 140 Milk, 150 c.c. (5 ounces) 105 Cream, 30 c.c. (1 ounce) 60 Lactose, 25 grams (7 drams) 100 VI. A. For 3900 calories a day': Milk, iy2 quarts (3500 c.c.) 1000 Cream, 1 pint (500 c.c.) 1000 Lactose, 36 ounces (480 grams) 900 This furnishes eight feedings, each containing: Milk, 6 ounces (180 c.c.) 120 Cream, 2 ounces (60 c.c.) 120 Lactose, 2 ounces (30 grams) 240 High Carbohydrate Typhoid Diet Recipes and Substitutes Arranged by Miss Edna Cutler for Dr. Coleman's work 1. Milk toast for toast and milk. 2. Cocoa with milk. Cocoa 25 gms. 50 Lactose 50 gms. 240 Milk 125 c.c. 80 Cream 50 c.c. 120 Mix sugar and cocoa, cook in milk until dissolved. Serve with cream. 292 METHODS IN MEDICINE 3. Cocoa. Cocoa 25 gms. 50 Lactose 50 gms. 240 Water 150 c.c. Cream 100 c.c. 180 Mix cocoa and sugar, add water and boil. Then add cream and serve with whipped cream. 4. Coffee. Lactose 25 gms. 120 Strong coffee 150 c.c. Cream 50 c.c. 120 5. Plain Junket or Bennet Custard. Lactose 25 gms. 100 Milk 150 c.c. 100 % Junket tablet. Cold water 25 c.c. Vanilla. 6. Cocoa Junket. Cocoa 25 gms. 50 Lactose 25 gms. 100 Milk 150 c.c. 100 % Junket tablet. Cold water 25 c.c. Mix cocoa and sugar, add milk and heat lukewarm, stirring constantly while adding the dissolved jun- ket. Stir thoroughly and leave in a cool place to set. 7. Soft Custard. Milk 250 c.c. 160 Egg, 1 80 Lactose 50 gms. 240 Speck salt. Vanilla. Caramel made from sugar. Beat the egg slowly, add sugar and beat milk slowly. Cook in double boiler, stirring constantly until it thickens a little. If it curdles, set in a dish of cold water and beat at once. Flavor and cool. 293 HIGH CALORIC TYPHOID DIETS 8. Baked Custard. Lactose 40 gms. 160 Milk 150 c.c. 100 Egg, 1 80 Speck salt. Nutmeg and vanilla. Beat egg slowly, warm sugar and milk, stir con- stantly, add the egg, strain in cup and flavor. Bake in pan in moderate oven until knife comes out clean. Thirty to 60 minutes. 9. Bread Pudding. Lactose 40 gms. 160 Milk 150 c.c. 100 Egg, 1 80 Bread 30 gms. 60 Butter 15 gms. 120 Spread bread with butter and cut in squares. Beat egg slightly, beat into milk and sugar, stirring con- stantly. Mix egg and pour over bread. Grate nut- meg and bake. 10. Lemonade. Lactose 125 gms. 480 Cold Water 200 c.c. Lemon Juice 30 c.c. Boil sugar and water 2 minutes, add lemon juice to taste, strain and cool. Vanilla Ice Cream for High Carbohydrate Typhoid Diet Cream (20%) 125 c.c. 350 Whole Milk 60 c.c. 45 Lactose 60 gms. 240 Speck of salt. Flavoring. 635 Syrup of fruit or chocolate may be substituted for vanilla. This makes a total of 6 large tablespoonfuls. References: Shaffer, P. A., and Coleman, W.: Jour. Am. Med. Assn., 1908, li, 974. Coleman, Warren: Arch. Int. Med., 1909, iv, 538. Jour. Am., Med'. Assn., 1909, liii, 1145. Am. Jour. Med. Sc., 1912, cxliii, 77. Me*d. Clinics of North Am., November, 1917, i, 513. 294 METHODS IN MEDICINE ARTHRITIS DIETS According to Pemberton sharp curtailment of food intake often influences greatly for the better, or relieves all symptoms in cer- tain cases of arthritis not amenable to other therapy. Additional support for such therapy was found in the blood sugar studies, which revealed a difficulty in the utilization of carbohydrate. The diets are based on the principle of a lowered intake. Not only are the calories reduced, but the proportions of the foodstuffs believed to be advantageous are provided. The caloric value ranges from 1650 cal. to 2100 cal. Of these calories, 10 per cent come from protein, 50 to 60 per cent from fat and 30 to 40 per cent from carbohydrate, thus providing a low caloric high fat, restricted or relatively low carbohydrate, and moderate protein diet. Reference: Pemberton, Ralph: Arch. Hit. Med., (April, 1920), xx, 335. Diet No. 1 Menus Arranged by Miss Cecile Davis, Barnes Hospital Weight in Grams Food 8 A.M. 12 M. 6 .P.M. ORDER Protein Fat Carbo- hydrate Calor. 4] 113 115 1641 Grapefruit 100 100 6 Cream 50 50 1 9 10 2 2 Bacon 20 20 1 9 13 4 Eggs Coffee ii ii 13 4 10 55 Sugar 22 22 22 Potatoes 75 75 1 6 7 13 5 Steak 75 75 14 7 9 5 Asparagus 100 100 1 5 11 2 3 (e) Pears 100 100 3 3 18 Butter 20 20 2 17 Consomme 100 100 2 2 Tomatoes 25 25 4 5 8 (c) Cream 45 45 1 9 9 Okra 100 100 7 1 2 9 Tomatoes 100 100 9 4 3 3 (f) Lettuce Oil 20 20 20 Olives 100 100 1 4 21 3 5 Orange Juice 100 100 8 2 11 6 Lemon Juice 50 50 4 9 Sugar 44 44 44 43 1 112 7 115 1643.5 (c) cooked. (f) fresh. LOW CALORIC ARTHRITIS DIETS 295 Diet No. 2. Weight in Grams FOOD 8 A.M. 12 M. 6 P.M. ORDER PROTEIN FAT CARBO- HYDRATE CALOR. 42 118 119 1700 Grapefruit 100 100 6 Bacon 20 20 1 9 13 5 Cream 75 75 1 8 15 2 5 Sugar 30 30 30 Coffee Cantaloupe 100 100 6 7 2 Consomme 200 200 4 4 Beets 100 100 1 6 1 8 6 Potatoes 75 75 1 9 .01 13 5 Steak 75 75 14 7 9 5 Tomatoes (c) 100 100 1 2 2 3 5 Butter 15 15 11 12 7 Olives 100 100 8 20 2 8 5 Oil 10 10 10 Lettuce Tomatoes (f) 75 75 G Ham 3 2 3 Bananas 75 75 11 2 29 1 Cream 100 100 1 3 6 21 Sugar 30 30 7 6 20 20 20 42 8 117 2 121 1 1710.4 Diet No. 3. FOOD 8 A.M. 12 M. 6.P.M. ORDER PROTEIN FAT carbo- hydrate CALOR. 51 118 195 2051 Cantaloupe 100 100 6 7 2 Cornflakes 25 25 1 1 3 9 20 2 Eggs 11 11 13 4 10 5 Egg albumin 35 35 4 3 Cream 100 100 2 5 20 4 5 Butter 10 10 1 8 55 Sugar 10 10 10 Bread 20 50 20 1 8 2 10 5 Chicken 50 50 10 5 1 5 Potato 100 100 2 2 1 18 Butter 10 10 1 8 5 Tomato (f) 100 100 9 4 3 3 Bread 20 20 1 8 2 10 5 Rice 25 25 2 19 7 Cream 100 100 2 5 20 4 5 Toast 20 20 1 8 20 2 10 5 Butter 28 28 2 23 8 Prunes 100 100 2 1 73 3 Egg white 35 35 4 3 51 3 117 8 192 2 2034.2 296 METHODS IN MEDICINE Diet No. 4. Weights in Grams FOOD 8 A.M. 12 M. 6-P.m. ORDER PROTEIN FAT CARBO- HYDRATE CALOR. 44 118 213 2090 Cream 100 100 2 5 20 4 5 Sugar 10 10 10 Butter 10 10 • 8 5 Shredded Wheat 20 20 2 1 1 15 2 Egg 1 1 6 7 10 5 Bacou Q5 25 2 4 16 8 Orange 100 100 8 2 11 6 Ham 50 50 8 1 19 8 Sweet Potato 100 100 1 8 7 26 1 Canned Corn 100 100 2 8 1 2 18 2 Raisins 50 50 1 3 1 7 38 Butter 18 18 15 3 Sugar 20 20 20 Cheese 10 10 8 3 5 Macaroni 25 25 4 1 7 Potato 100 100 2 2 1 18 Cream 25 25 6 5 8 1 1 Butter 15 15 12 7 Bread 75 75 3 9 8 39 3 Sugar 5 5 5 42 118 8 214 2086 Reduction Diet Arranged by Miss Dorothy M. Stewart, University of Michigan Hospital, Ann Arbor Protein.-Two-thirds gram per kilogram of normal body weight for adults; for children 1% grams. Calorics.-Not more than % the normal requirement-to be ob- tained from bulky vegetables and fresh or unsweetened cooked fruits. Breakfast.- Fruit without sugar. Light cereal,-puffed wheat, puffed rice or corn- flakes with milk,-no sugar. % slice unbuttered toast. Coffee without cream, sweetened with saccharin if desired. LOW CALORIC REDUCTION DIETS 297 Dinner.- Clear soup. Lean meat-chicken or fish. Vegetables-two large servings either hot or as salad with vinegar. Tea. Water. Supper.- Cold meat (lean) or eggs. Vegetables-1 large serving. Fresh fruit or fresh dessert sweetened with sac- charin if desired. Tea. Milk. Low Caloric Value Diet Breakfast - calories Any fresh fruit 40-90 Cereal 60 Toast, 1. slice 60 Lunch.- Bouillon Consomme Vegetable Beef Soup 120 c.c. 30 Lean meat 90 gms. Fish 90 gms. Cabbage Cauliflower Celery Cucumber Carrots String beans Parsnips Turnips as desired 50 Bread-wheat-1 slice 100 or Bran gems (2 small ones) Butter (very small amount) 100 Buttermilk (1 glass) 80 or 200 c.c. Clear tea (no sugar) 00 298 METHODS IN MEDICINE Supper.- CALORIES Lean meat 90 gms. 200 Vegetables (as for lunch) 50 Bread (as for lunch) 100 Clear tea (no sugar) 00 Total calories 1120 Obesity Diet 6 A.M. CALORIES Tea 250 c.c. Ham (boiled) 50 gm. 180 Toast 40 " 120 10 A.M.- Fresh Fruit 12 Noon.- Clear soup 250 c.c. Lean meat 100 gm. 400 Green vegetables 100 " 20 Salad without oil 50 " 50 2 p.m.- Fresh Fruit 4 p.m.- Tea 250 c.c. 6 p.m.- Lean Meat 75 gm. 300 White Potato 50 " 60 Sour Pickle 8 p.m.- Fresh Fruit 40-90 "1220 Breakfast.- 2 eggs (poached or boiled) without butter. Coffee, with saccharine and 2 drams milk, if desired. 1 oz. bread without butter. LOW CALORIC REDUCTION DIETS 299 Dinner.- 1 cup of broth or vegetable soup, skimmed of fat. 4 oz. lean meat, no starchy gravy. 4 oz. potato, baked or boiled, without butter. Salad of lettuce, tomato, fresh cucumbers-no oil. 4 oz. fresh fruit. Afternoon Tea.- 1 cup of tea, saccharine and milk. 1 oz. bread, no butter. Supper.- 4 oz. lean meat. 2 oz. potato, or cauliflower, spinach or cabbage. 4 oz. fresh fruit. Black coffee. Total calories = 1267 Directions for Those Overweight 1. Avoid all fats. 2. Avoid sugar and candy. 3. Do not eat between meals. If you get hungry, eat a piece of celery or drink water. 4. Do not drink water with the meals, but between meals, on getting up, and on going to bed. 5. Take plenty of exercise. 6. If you wish to reduce faster, eat less and exercise more. CHAPTER XX DIETS IN GASTROINTESTINAL DISEASES LENHARTZ'S ULCER DIET First Day.- Milk, 25 c.c., at 6, 8, 10, 12, 2, 4, 6, and 8 o'clock. Beaten eggs, 16 c.c., at 7, 9, 11, 1, 3, 5, and 7 o'clock Second Day.- Milk, 37 c.c., at 6, 8, etc. Beaten eggs, 24 c.c., at 7, 9, 11, etc. Third Day.- Milk, 50 c.c., at 6, 8, etc. Eggs, 30 c.c., at 7, 9, etc. Sugar, 20 grams, (added to beaten eggs). Fourth Day.- Milk, 62 c.c., at 6, 8, etc. Eggs, 40 c.c., at 7, 9, etc. Sugar, 20 grains, (added to beaten eggs). Fifth Day.- Milk, 75, c.c., at 6, 8, etc. Eggs, 48 c.c., at 7, 9, etc. Sugar, 30 grams, (added to beaten eggs). Sixth Day.- Milk, 87 c.c., at 6, 8, etc. Beaten eggs, 56 c.c., at 7, 9, etc. Sugar, 40 grams, (added to beaten eggs). Scraped beef, 12 grams, at 8, 12 and 4 o'clock. Seventh Day.- Milk, 100 c.c., at 6, 8, etc. Beaten eggs, 30 c.c., at 7, 9, etc. One soft boiled egg at 6, 10, 2 and 6 o'clock. Scraped beef, 23 grams, at 9, 1 and 5 o'clock. Rice, boiled, 33 grams, at 8, 12 and 4 o'clock. Sugar, 40 grams, (added to beaten eggs or to rice). 300 301 ULCER DIETS Eighth Day.- Milk, 112 c.c., at 6, 8, etc. Beaten eggs, 30 c.c., at 7, 9, etc. One soft boiled egg at 6, 10, 2 and 6 o'clock. Scraped beef, 23 grams, at 9, 1 and 5 o'clock. Boiled rice, 33 grams, at 8, 12 and 4 o'clock. Sugar, 40 grams, (added to beaten eggs or to rice). Ninth Day - Milk, 125 c.c., at 6, 8, etc. Beaten eggs, 30 c.c., at 7, 9, etc. One soft boiled egg at 6, 10, 2 and 6 o'clock. Scraped beef, 23 grams, at 9, 1 and 5 o'clock. Boiled rice, 66 grams, at 8, 32 and 4 o'clock. Zwieback, 20 grams, at 9, and 5 o'clock with scraped beef. Sugar, 40 grams, (added to beaten eggs or to rice). Tenth Day.- Milk, 125 c.c., at 6, 8, etc. Beaten eggs, 30 c.c., at 7, 9, etc. One soft boiled egg at 6, 10, 2 and 6 o'clock. Scraped beef, 23 grams, at 9, 1, and 5 o'clock. Boiled rice, 66 grams, at 8, 12 and 4 o'clock. Zwieback, 20 grams, at 7 and 5 o'clock. Chicken (chopped), 50 grams, at 11 o'clock. Butter, 30 grams, at 7 and 5 o'clock (with zwieback). Sugar, 40 grams, (added to beaten eggs or to rice). Eleventh Day.- Milk, 125 c.c., at 6, 8, etc. Beaten eggs, 30 c.c., at 7, 9, etc. One soft boiled egg, at 6, 10, 2 and 6 o'clock. Scraped beef, 30 grams, at 9, 1 and 5 o'clock. Boiled rice, 100 grams, at 8, 12 and 4 o'clock. Zwieback, 30 grams, at 7 and 5 o'clock. Chicken (chopped), 50 grams, at 11 o'clock. Butter, 20 grams, at 7 and 5 o'clock (with zwieback). Sugar, 50 grams, (added to beaten eggs or to rice). 302 METHODS IN MEDICINE Twelfth Day.- Milk, 125 c.c., at 6, 8, etc. Beaten eggs, 30 c.c., at 7, 9, etc. One soft boiled egg, at 6, 10, 2 and 6 o'clock. Scraped beef, 23 grams, at 9, 1 and 5 o'clock. Boiled rice, 100 grams, at 8, 12 and 4 o'clock. Zwieback, 30 grams, at 7 and 5 o'clock. Chicken (chopped), 50 grams, at 11 o'clock. Bntter, 20 grams, at 7 and 5 o'clock (with zwieback) Sngar, 50 grams, (added to beaten eggs or to rice). Thirteenth Day.- Milk, 125 c.c., at 6, 8, etc. Beaten eggs, 30 c.c., at 7, 9, etc. One soft boiled egg, at 6, 10, 2 and fi o'clock. Scraped beef, 23 grams, at 9, 1 and 5 o'clock. Boiled rice, 100 grams, at 8, 12 and 4 o'clock. Zwieback, 40 grams, at 7 and 5 o'clock. Chicken (chopped), 50 grams, at 11 o'clock. Butter, 20 grams, at 7 and 5 o'clock (with zwieback) Sugar, 50 grams, (added to beaten eggs or to rice). Fourteenth Day.- Milk, 125 c.c., at 6, 8, etc. Beaten eggs, 30 c.c., at 7, 9, etc. One soft boiled egg, at 6, 10, 2 and 6 o'clock. Scraped beef, 23 grams, at 9, 1 and 5 o'clock. Boiled rice 133 grams, at 8, 12 and 4 o'clock. Zwieback, 50 grams, at 7 and 5 o'clock. Chicken (chopped), 50 grams, at 11 o'clock. Butter, 20 grams, at 7 and 5 o'clock (with zwieback) Sugar, 50 grams, (added to beaten eggs or to rice). Modified Leniiartz's Ulcer Diet Barnes Hospital CALORIES EGGS CREAM MILK DIRECTIONS 300 1 45 120 Mix give q. 1. h. 15 c.e. 7 A. m.-7 q. M. 600 o 90 240 " << lf 30 << (< << 900 3 135 360 " << << 45 << << 1200 4 180 480 " " " 60 " " " 1500 5 225 600 " " << 75 (< << << 1800 6 270 720 " " " 90 " " " 6 280 600 " " " 90 " " " ULCER DIETS 303 First Day.-Cal.- 300. 1 Egg, Cream 45, Milk 120. Mix and give 15 c.c. q. hour from 7 A. M. to 7 P. M. Second Day.-Cal.- 600. 2 Eggs, Cream 90, Milk 240. Mix and give 30 c.c. q. hour from 7 A. M. to 7 P. M. Third Day.-Cal. - 900. 3 Eggs, Cream 135, Milk 360. Mix and give 45 c.c. q. hour from 7 a. m. to 7 P. M. Fourth Day.-Cal.-1200. 4 Eggs, Cream 180, Milk 480. Mix and give 60 c.c. q. hour from 7 a. m. to 7 P. M. Fifth Day.-Cal.-1500. 5 Eggs, Cream 225, Milk 600. Mix and give 75 c.c. q. hour from 7 A. M. to 7 P. M. Sixth Day.-Cal.-1800. 6 Eggs, Cream 270, Milk 720. Mix and give 90 c.c. q. hour from 7 A. M. to 7 P. M. Seventh to tiie Tenth Day.-6 Eggs, Cream 180, Milk 600. Mix and give 90 c.c. at 8, 9, 10, 11, 12 a. m. and 2, 3, 4, 5, 6 P. M. Oatmeal-strained 2 tablespoon-' fuls. Cream-60 c.c. Sugar-1 level teaspoonful. 1 Egg-soft boiled. >at 7 A. m. and 7 P. M. Cal.-2100 Scraped beef-lightly boiled 1' rounded tablespoonful. Rice, 1 heaping tablespoonful. Milk-90 c.c. •at 1 p. m. Eleventh to Fourteenth Day.- /2 Eggs-soft boiled. Toast-1 slice, 30 grams Butter-15 grams, 1 pat. Cream of wheat or strained oatmeal-3 tablespoonfuls , Cream-90 c.c. Sugar-1 tablespoonful. Scraped beef or minced breast of chicken-2 tablespoonfuls. i Dry toast-slices-40 grams Rice, 2 heaping tablespoonfuls. Butter, 15 grams. Ice Cream-2 tablespoonfuls. 1 Egg. Cream-30 c.c. k Milk-90 c.c. at 7 A. M. and 7 P. M. Cal.-2800 at 1 p. M. Mix and give all at 9 and 11 A. M. and 3 and 5 P. M. Fifteenth to Twenty-First Day.- Approximate Calories-3000 Same as from eleventh to fourteenth days, except that the amount of cereal, cream and chicken or beef may be increased; baked Irish potatoes may be substituted for rice, and gelatin or boiled custard for ice cream. Third to Sixth Week:* Approximate Calories-3500 The diet should be same as in third week except that strained orange juice may be given for breakfast and purees of peas, beans and potatoes may be given for dinner. Soft green vegetables mashed through sieve may be added. 304 METHODS IN MEDICINE Notes: The egg, milk and cream mixture should be kept in a covered dish with ice packed around it. The amount for each feed- ing should be given slowly and with a spoon, and with the same exactness and regularity as if it were medicine. The scraped beef should be made into a patty and lightly broiled with a little butter and salt. Rice and oatmeal should be cooked for several hours. The dry toast should be in slices 4 x 4% inches in size. Tl]e crust should be removed and the patient instructed to chew it until it becomes liquid with saliva. Orange juice 125 grams = 50 calories. Hot malted milk 250 c.c. = 160 calories. Formula for a Day's Ration.- Milk-1500 c.c. ' Cream-480 c.c. Lactose-240 c.c. = 8 feedings. References: Lenhartz: Deutsch, med. Wchnschr., 1904 and 1906. Tberap. d. Gegenwart, January, 1913. 20th and 26th Kong. f. inn. Mod. Med. Clin., 1915, iii. Lambert, S.: Am. Jour. Med. Sc., December, 1904. Harris, S.: Southern Med. Jour., November, 1916. SIPPY ULCER DIET Milk and 40 per cent Cream, aa. I). 90 c.c. at 7, 8, 9, 10, 11, 12, 1, 2, 3, 4, 5, 6, 7, 8, (9-10?) if awake. I>. Sod. bicarb. Bismuth subcarb. 0.6 gm. aa 0.6 gm. at 7:30, 9:30, 11:30, 1:30, 3:30, 5:30, 7:30, 9:30 I/. Mag. Oxide Sod. bicarb. 0.3 gm. at 8:30 10:30, 12 :30, 2 :30, 4:30, 6:30, 8:3'0 0.6 gm. Regulate antacids to control acidity and pain. Aspirate con- tents each evening two hours after last powder and estimate the acidity. Attempt to get neutralization of acidity. Reference: Sippy, Bertram W.: Jour. Am. Med. Assn., Mav, and June, 1915, Ixiv, 1625 2090. 305 ULCER DIETS Modified Sippy Diet Peter Bent Brigham Hospital, Boston (Musser and Kelly) MORNING HOUR 6 7 8 9 10 11 12 DAY 1st Milk 60 c.c. Albumin Water 90 c.c. Milk Albumin Water Milk Albumin Water Milk 2 Cream 30 c.c. Cream Cream Cream 3 1 egg 4 Cereal 90 c.c. or gm. 5 Puree 90 c.c. or gm. 6 Bacon 2 slices- crisp 7 Broth 90 c.c. AFTERNOON AND EVENING HOUR 1 2 3 4 5 6 7 8 9 10 DAY 1st Milk Albu- min Water Milk Albu- min Water Milk Albu- min Water Milk Albu- min Water Milk Albu- min Water 2 Cream Cream Cream Cream Cream 3 Egg 4 Cereal 5 Egg(l) Puree 6 Bacon Bacon 7 Broth Broth The diets for the eighth to the fourteenth clays are similar to the diet of the seventh day with the addition of half a slice of toast at any three feedings. Custard 90 c.c. or gm. may be sub- stituted for any milk or albumin water feedings. The food substances enumerated are added each day to the first and succeeding days' diets at the specified hours. 306 METHODS IN MEDICINE Methods of Preparing Foods and Notes Albumin Water.-To the white of one egg add enough water to make 90 c.c. Flavor with orange or lemon juice or vanilla. Use no sugar. (Serve as albumin water in the schedule.) Cereals.-Cereals should be soft and well cooked. Measure after cooking. Ralston's, Farina, Cream of Wheat, or boiled rice may be used. Puree.-Cream of peas, corn, spinach or celery, (strained or run through a colander). Bacon.-Two slices which should be fried crisp. Broth.- (Clear) chicken, oyster, or clam stock. Water intake.-Water intake is not limited. Medicine.-Give % teaspoonful of Ty- Sod. Bicarb. 50 gm. Mag. Oxide (ponde) 50 gm. in % glass of water after every feeding. Management.-Give nourishment every hour from 6 a.m. to 9 p.m. and on succeeding days additional feedings are to be taken at the hours indicated. Do not discontinue a feeding that has been started on any previous day. The amount of any food used, as indicated in the first feeding thereof, should remain constant. Hurst's Modified Sippy Diet Put teeth into perfect condition; treat and eliminate any in- fected focus in the nose and throat. Keep the mouth absolutely clean. Scrape the tongue with a wooden spatula if it becomes furred. If a chronic appendicitis is present, appendix should be re- moved. Keep patient warm in bed, but allow up for daily bath and daily bowel movement. 1. One hundred fifty c.c. (oz. v) of milk (or preferably milk and cream in equal parts) are given every hour from 8 a.m. to 8 p.m. inclusive. 2. Add to each feeding: Sodium citrate 0.6 gm. (gr. x) Emulsio magnesiae 8.0 c.c. (drams ii) Magnes. oxid. (ponde) 0.6 gm. (gr. x) ULCER DIETS 307 The sodium citrate combines with the lime in the milk and con- sequently prevents the formation of irritating clots by rennin of the gastric juice. The calcined or heavy magnesium oxide has the advantage over sodium bicarbonate in having four times the neutralizing power; and in not giving off C02 and distending; in having a mild aperient action; and in producing a very much smaller secondary increase in gastric secretion, after the initial neutralization, than sodium bicarbonate does. The latter is the most powerful stimulant of gastric secretion in existence. 3. Immediately before alternate feedings, beginning at 7:30 a.m., 15 c.c. (% oz.) of olive oil is taken. 4. Immediately before the remaining feedings and at 9, 9:30 and 10 p.m. give a powder containing: Calcium carbonate 0.6 gm. (gr. x) Bismuth carbonate 2.0 gm. (gr. xxx) 5. At 6 a.m. give a powder containing: I£. Bismuth carbonate 15 gm. (% oz.) Water 150 to 300 c.c. (5-10 oz.) When shaken up, but not suspended, and taken by mouth with the patient lying on his right side, in a position such that the powder is likely to come in contact with the ulcer, there is a protective covering formed. 6. If there is pylorospasm with resulting stasis at 11 p.m. the stomach is completely emptied by Senoran's evacuator. If not more than 60 c.c. (oz. ii) of fluid are present on two con- secutive nights, this can be discontinued. If 125 c.c. or more are removed at 11 p.m. the stomach should be evacuated again at 1 a.m. 7. At 11 p.m., if there is evidence of stasis, atropine sulphate 0.001 gm. (%0 Sr-) is injected subcutaneously. At the same time the alkaline powder should be given and if more than 60 c.c. of fluid were evacuated, the powder should be repeated every two hours through the night. 8. If the patient is constipated, the dose of magnesia should be increased and, if the bowels do not move on two consecutive days, an enema should be given. If diarrhea occurs, some of the mag- 308 METHODS IN MEDICINE nesia should be replaced by an equivalent amount of bismuth car- bonate. 9. This strict treatment is carried out until for three weeks the patient has had no spontaneous pain, no trace of tenderness has been present, no occult blood has been found in the stools, not more than 60 c.c. of fluid has been removed on any one evening and the x-ray shows no evidence of active ulceration. Then the diet can be rapidly increased, omitting, however, all irritants. Reference: Hurst, Arthur F.: Brit. Med. Jour., April 24, 1920, p. 559. MILLS' ULCER DIET List No. 1 Used in acute cases. Breakfast.- Oatmeal jelly (well cooked, strained). Soft boiled eggs (coddled seven minutes). Hot water and cream (% cream). 10:30 a.m.- Glass of half milk and cream. Noon.- Soft boiled eggs (coddled seven minutes) Toast soaked in hot water, add cream. Custard, gelatine, blancmange, cornstarch. Hot water and cream (% cream). 4 p.m.- Glass of half milk and cream. Night.- Same as at noon. Used in subacute cases. Breakfast.- Thoroughly cooked and strained Cream of "Wheat, or Farina, with cream and little sugar. One soft boiled egg (coddle seven minutes). One cup hot water and cream (% cream). List No. 2 309 ULCER DIETS 10:30 a.m.- Crumbled crackers in warm milk, or crumbled stale bread (soft part only) in warm milk, or glass of % lactose or fermillac, or milk and % cream. Noon.- Milk toast. Thin dry toast and butter. Oatmeal jelly, or oatmeal (most thoroughly cooked, strained, and allowed to cool). Cup of hot water with cream (% cream). 4 p.m.- Same as at 10:30 a.m. Night.- Two soft boiled eggs (coddled seven minutes). Thin dry toast and butter. Custards, gelatine, cornstarches, junket, blancmange. Cup hot water and cream (% cream). 10 P.M. Same as at 10:30 a.m. List No. 3 Used during convalescing stages when free from pain. Breakfast.- Thoroughly cooked Cream of Wheat, Farina or Corn Flakes, with cream and a little sugar. Eggs: soft boiled (coddled seven minutes). Stewed prunes-skins not to be eaten. Milk toast (made from stale white bread) and served with unsalted butter. One cup hot water and cream (% cream). Noon.- Eggs: soft boiled (coddled seven minutes). Tender roast breast of turkey, chicken or squab (without dressing). Scraped beef (mixed with the white of an egg and broiled). 310 METHODS IN MEDICINE Fresh fish baked, white meat only. (Crappie, Bass, Whitefish.) Rice well cooked. Thin dry toast and unsalted butter. Milk toast and unsalted butter. Stewed prunes-skins not to be eaten. Custards, gelatines, cornstarches, tapioca, junket, blancmange; all made with but little sugar. One cup hot water and cream (% cream). Night.- Same as at noon. Use butter and cream freely. All food must be very well cooked. List No. 4 Used during interim between ulcer attacks and on which patient is kept indefinitely. Breakfast.- Stewed apples (not tart), stewed prunes. Shredded Wheat Biscuits, well cooked Cream of Wheat, Farina or Quaker Oats with cream and sugar. Eggs: poached, soft boiled (coddled seven minutes). Toasted graham or whole wheat bread and butter. One cup hot water and cream (% cream). Noon.- Eggs: poached, soft boiled (coddled seven minutes), omelet. Cottage cheese with cream. Creamed spinach, asparagus, tender string beans, peas, well mashed squash, stewed creamed white onions, stewed creamed carrots. Graham or whole wheat bread and butter. Stewed apples, stewed prunes, baked apples. Custards, gelatines, cornstarches, tapioca, junket, blancmange. Soft ice cream with bread and butter. One cup hot water and cream (% cream), or Glass of cool water. BLAND DIETS 311 Night.- Tender roast beef, roast lamb, roast chicken (without dressing) or stewed creamed chicken. Broiled steak, broiled lamb chops (lean portion only). Stewed sweetbreads, or calves' brains. Baked fresh fish. (Crappie, Bass or Whitefish.) Potatoes well mashed or baked, or rice well cooked. Other vegetables same as at lunch. Graham or whole wheat bread and butter. Desserts same as at lunch. One cup hot water and cream (% cream). Reference: Mills, R. Walter: Barnes Hospital, St. Louis, Mo., Personal Communication. Bland Diet First Day.-Every three hours. Milk 60 c.c. Uneeda biscuit 4 Sugar q.s. Give crackers to patient to break into bowl of milk, add sugar to suit taste, and feed every three hours. Second Day.- Increase the above diet in frequency and amount, so as to total twice the amount of the first day. If necessary keep up for two weeks to relieve gastric symptoms. Nonresidue Forming or Nonlaxative Diet for Diarrheal Cases Clear Meat Soups. Eggs. Mashed or Baked Potatoes. Macaroni. Rice. Spaghetti. Cream of Wheat. Cheese. Corn-meal Mush. Lean Meats. White Breads. Bananas. r'" Milk (preferably boiled). 312 METHODS IN MEDICINE Coarse Diet Use: Oatmeal Melons Bran mush Dried fruits Bran mush muffins Raisins Brown, Graham, or Potatoes Whole wheat wafers, etc. Celery Corn meal Raw Oysters Grits Poultry Cracked wheat Salad oil Shredded wheat String Beans Prunes Corn Figs Asparagus Gelatins Spinach Ice Cream Onions Ices Cauliflower Fruits (all kinds) Fruits.- All fresh fruits. All stewed fruits. Dates. Prunes figs, stewed raisins are especially laxative. Vegetables.- Lettuce Asparagus Tomatoes Cauliflower Celery Cabbage Radishes Irish potatoes Cucumbers Sweet potatoes Peas and beans Carrots Sweet corn Egg plant Parsnips Beets All greens Turnips and rutabagas Spinach and onions are especially laxative. Cereals.- Rolled oats with bran. Bran bread, biscuits, and muffins. Bran preparations. Shredded wheat. Graham bread. Laxative Dietary COARSE DIETS 313 Miscellaneous.- Plain vegetable broths and soups. Cream for coffee Fruit jellies and marmalades. Butter. Honey. Olive oil. Buttermilk. Fish and bacon. Can NOT have meat, milk, or eggs. Spastic Constipation (Forcing soft laxative elements, cooked, with unlimited fruit and vegetables.) Breakfast.- Eight stewed prunes (without skins), one grape fruit (cut across and eaten with a spoon), or apple sauce. Well cooked cream of wheat, oatmeal, farina or shredded wheat biscuit, corn flakes. Soft-boiled or poached eggs. Graham or whole wheat bread and butter. Cup of hot water and cream (less desirably, hot water and milk). At Noon.- Creamed and strained vegetable milk soup of po- tato, pea. celery, barley (mashed), vermicelli. Eggs : soft-boiled or poached. Vegetables: creamed or plain cooked and with drawn butter, spinach, asparagus, celery (ten- der), green peas (tender), tender string beans, tender white onions, cauliflower, mashed squash, mashed carrots. Mashed or baked potatoes. Graham, whole wheat or white bread and butter. Warm apple sauce, baked apple pulp, stewed peaches or apricots. Cup of hot water and cream (less desirably, hot water and milk). (Eat much of these foods.) 314 METHODS IN MEDICINE At Night.- Same as at noon, except no soup. In addition, tender baked or broiled mutton, beef, chicken, squab, or steak, lamb chops, baked or boiled crappie, bass or whitefish. Custard, gelatine, blancmange, cornstarch, prune whip, tapioca, sago. Use no condiments, little salt or sugar. Vegetables to be well cooked, without addition of meat, grease or butter. Canned vege- tables may be used. Atonic Constipation (Forcing coarse laxative elements, unlimited raw and cooked veg- etables and fruits with coarser cereals and other stimulating foods.) Breakfast.- Orange, grape fruit or cantaloupe, stewed apples, stewed prunes. Shredded wheat biscuits, cream of wheat, corn- flakes or rolled oats with cream and sugar. Eggs: soft-boiled, seven-minute or poached. Corn muffins, graham muffins, with butter and honey. One cup hot water and cream (% cream), or one cup coffee. At 10 a.m.- One glass cool water. At Noon.- Vegetable soups. Onions, raw or cooked, radishes, olives, celery, Brussels sprouts, sauerkraut, cabbage, cold slaw, cauliflower, peas, lima beans, okra, stewed or baked tomatoes, baked or broiled egg plant, carrots, spinach, asparagus, string beans, squash, well mashed turnips, stewed celery. COARSE DIETS 315 Stewed fruits (large dish), apples, peaches, apri- cots, pears, pineapples, cranberries. Raw fruits (except bananas). Salads with mayonnaise or French dressing. Graham, whole wheat, rye or corn bread, or corn muffins, with butter and honey or syrup. One glass buttermilk or cool water. (Eat much of these foods.) At 3 p.m.- Same as at 10 a.m. At Night.- Soups, stewed fruits, raw fruits, vegetables, and breads, as at lunch. All roast, stewed and broiled meats. Potatoes, well mashed, baked, boiled, French fried or German fried. Sliced oranges, sliced pineapple. Glass cool water. Nuts. Molasses candy. Canned vegetables and fruits may be used. Schmidt's Intestinal Diet 7 A.M. Milk 500 c.c. Roll 1 Butter 10 gm. Egg, 1 soft boiled Tea 250 c.c. 8 A.M. Oatmeal 40 gm. Butter 10 gm. Milk 200 c.c. Water 300 c.c. Salt q.s. Cook, strain and add sugar to taste. 316 METHODS IN MEDICINE 12 M.- Beef, lean, fine chopped 100 gm. cooked with butter White potato 200 gm. Milk 100 c.c. Butter 10 gm. 5 P.M.-- Same as 6:30 a.m. 8 p.m.- Same as at 7:30 with Egg, 1, beaten into oatmeal gruel. For Schmidt-Strasburger Diets, see page 142. For Mosenthal Renal Test Diets, see page 162. CHAPTER XXI IMPORTANT ORGANIC AND INORGANIC CHEMICAL CONSTITUENTS IN DIETS THE TREATMENT OF GOUT Purin-Free Diets in Gout GIVE foods of Low Purin AVOID foods of High Purin Content as Content as Dairy Products.-- Meats and Fish (given in order Milk of purin content) Butter Sweetbreads (Thymus or Pan- Cottage creas) Cream or Brains, Liver, Kidney Swiss Beef Cheese Malted Milk Fish Eggs Poultry Nuts Veal Pork Mutton Game Cereals.- Cornflakes Oatmeal Shredded wheat Cream of wheat Farina Rice Hominy Bread.-■ Wheat (white) Graham bread Crackers 11 Whole wheat bread Bran bread 317 318 METHODS IN MEDICINE Purin-Free Diets in Gout-(Cont'd) GIVE foods of Low Purin AVOID foods of High Purin Content as Content as Vegetables.- Lettuce Peas Cabbage Beans Eggplant Asparagus Cauliflower Onions Potatoes (small amounts) Mushrooms Sweet potatoes Potatoes (large amounts) Corn Okra Brussels sprouts Soups.- Puree Meat stocks Cream Extractives Noodles Macaroni Desserts.- Pudding Bread or cornstarch Rice or tapioca Custard or coconut pie Gelatin preparations Stewed or preserved fruits Ice cream or Ices Cake (No chocolate or coffee flavors) Beverages.- Decaffeinated Coffee (Kaffee Coffee Hag) (small amount) Tea Milk Cocoa Fruit juices, especially grape juice, cider Carbonated waters IMPORTANT ORGANIC AND INORGANIC DIET CONSTITUENTS 319 Cholesterin and Lipoids in Diets According to Rothschild and Rosenthal, the dietetic treatment in cases of hypercholesterinemia consists in diminishing the intake by using foods of low cholesterin content, and by rendering the absorption of cholesterin as difficult as possible by decreasing the lipoid content and rendering difficult the intestinal esterization of the free cholesterin. A fat-free diet answers both purposes. Foods rich in lipoids, to be excluded in hypercholesterinemia, are: eggs, cream, butter, cheese, milk, meat, fish, especially salmon, shad, and bluefish. Vegetables rich in phytocholesterin, consequently to be excluded, are : beans and peas. The strict practically lipoid-free diet is made up of vegetables other than those mentioned. Cereals, sugars, carefully skimmed milk, and fat-free buttermilk are allowed. This strict diet is adhered to for three or four days during which the body is depleted of stored-up lipoids. The patient usually de- mands a change at the end of this period and a more liberal diet is permitted for three or four days. During the period of the liberal diet, in addition to the lipoid- free menu the patient is allowed moderate quantities of well cooked lean meat and fish of any kind other than salmon, shad, or blue- fish. Oleomargarin is substituted for butter. Reference: Rothschild, M. A., and Rosenthal, N.: Am. Jour. Med. Sc., Sept., 1916, clii, 394. Average Amounts of Cholesterol in Foods Luden, in the course of studies on cholesterol, determined the amounts of cholesterol in the usual foodstuffs by the Bloor Meth- ods I and JI. It is pointed out that the cholesterol content of foods varies according to a number of factors, and consequently an extremely large number of determinations would be necessary in order to secure absolute data. The table of Luden is neverthe- less very valuable; with minor modifications as to order, and the omissions of the results by the older methods, it is as follows: 320 METHODS IN MEDICINE DUBOSCQ BLOOR I FOOD MG. PER 6 C.C. CHCI3 COLORIMETER BLOOR II MG. PER 6 C.C. CH Cl 3 Yolk of egg, desiccated 4.000 4.000 Yolk of egg, hard boiled 49% water 2.660 2.660 Yolk of egg, raw 3 grams 2.660 2.660 Butter 3 grams .472 .880 (Tcoloring matter) Mushrooms (agaricus campestris) .444 .307 Chicken roasted, breast .380 .380 Fish black bass .250 .250 Mushrooms (agaricus campestris) with sauce .210 .181 Beef roast .190 .190 Cream, raw 3 c.c. .185 .185 Beef, smoked dried .181 .250 Beef, raw 3 grams .160 .160 Milk, raw 3 c.c. .080 .080 Oatmeal 0.000 0.000 Cholesterol in Foods Reference: Luden, Georgine: Jour. Lab. and Clin. Med., Dec., 1917, iii, 141. Iron in Foodstuffs High iron diets and low iron diets may be arranged by selections from the accompanying tables (page 321). Approximate Iron Content of Foods Vegetables, 5.3 to 1 per cent.-Lettuce, onions, asparagus, spinach, endive, kohlrabi, pumpkins, artichokes, tomatoes, lentils, black radishes, celery, rhubarb, potatoes, mushrooms, beets. Berries, 5 to 1 per cent.-Strawberries, gooseberries, huckleberries. Fruits, 2 to 1 per cent.-Figs, pineapples, apples, pears, plums. Nuts 1.8 to 1.3 per cent.-Coconuts, walnuts. Cereals, 2 to 1 per cent.-Rye flour, barley meal, barley flour, rice, buckwheat flour, cornmeal, corn flour, rice flour, wheat, wheat flour, graham flour. One hundred twenty gm. of beefsteak contain 4.7 mg. of iron; 110 gm. oatmeal, 3.1 mg.; 500 c.c. milk, 2.2 mg.; 300 gm. fine bread, 1.8 mg.; 100 mg. spinach, 4.5 mg.; 100 gm. yolk of egg, 4 mg.; egg white and wheat, 2.6 mg.; 100 gm. oatmeal, lentils, white beans and peas, 2.4 mg. IMPORTANT ORGANIC AND INORGANIC DIET CONSTITUENTS 321 Percentage of Iron in Food Materials PEI FOOD MATERIAL 0 l CENT F IRON PER CENT OF IRON Beans, lima, dried 0.0072 Whole-wheat bread .0013 Beans, pea, dried .0067 Potatoes, edible portion .00125 Wheat breakfast food used in Corn meal .00115 dietary study No. 486 .0057 Bread .0010 Roots (beets, carrots, parsnips, radishes, sweet potatoes, tu Potatoes, as purchased .0010 r- Green vegetables (asparagus, nips) .006 cabbage, celery, collards, Peas, dried .0056 greens, lettuce, onions, rhu- Raisins .0036 barb) .0008 Oatmeal and other breakfast Peas, canned .0008 cereals .0036 Rice .0008 Eggs, edible portion .0030 Bananas, edible portion .0008 Spinach .0030 Corn, canned .0007 Corn, dried .0029 Pumpkins .0006 Prunes, edible portion .0029 Squash .0006 Prunes, as purchased .0025 Vegetable soup, canned, con- Milk .0024 densed .0005 Whole-wheat flour .0020 Bananas, as purchased .0005 Peanuts .0020 Tomatoes, fresh or canned .0004 Chocolate .0020 Apples, fresh .0003 Beans, string .0016 Canned and preserved fruit, jel- Cheese .0015 lies, jam, Oranges and lemons, edible .0003 Peas, fresh .0015 Wheat flour, crackers, and maca- portion. .0002 Toni .0015 Cream .0002 Apples, evaporated Grapes .0014 0.0013 Cucumbers .0001 Amounts of Iron in Dried Food Substances MG. OF IRON ■■ MG. OF IRON PER 100 GM. PER , 100 GM. Blood serum 0.000 Black cherries, without stones 7.2 White of hen's eggs Trace White beans 8.3 Rice 1.0-20 Carrots 8.6 Pearl barley 1.4-1.5 White bran 8.8 Wheat flour, (sifted) l.G Strawberries 8.6-9.3 Cows' milk 2.3 Linseed 9.5 Human milk 2.3-3.1 Unpeeled almonds 9.5 Goat's milk 3.2 Red cherries, without stones 10.0 Figs 3.7 Brown skinned hazel nuts 13.0 Raspberries 3.9 Apples 13.0 Hazel-nut kernels 4.3 Dandelion leaves 14.0 Barley 4.5 Cabbage, outer green leaves 17.0 Cabbage (inside yellow leaves) 4.5 Beef 17.0 Rye 4.9 Asparagus 20.0 Peeled almonds 4.9 Yolk of egg 10-24. Wheat 5.5 Spinach 33-39. Bilberries 5.7 Pigs' blood 226.0 Potatoes 6.4 Hematogen 290.0 Peas 6.2-6.6 Hemoglobin 340.0 322 METHODS IN MEDICINE About 10 mg. iron is the estimated intake per clay filling require- ment. References: Bulletin, U. S. Department Agriculture; Dept. Chemistry Exp. Station No. 45 and No. 185. Von Bunge, G.: Ztschr, f. Biol., 1904, (N. F. 27), xlv, 532. Hoobler, B. P.: Arch. Pediat., 1912, xxix, 208. Calcium, in Foodstuffs High calcium diets and low calcium diets may be arranged by making selections from the tables of foods arranged according to the calcium content. Percentage or Calcium in Food Materials Gm. per ICO gm. Gm. per 100 gm. Vegetables: Cream .147 Turnips .870 Eggs .100 Greens, turnip tops .508 Oatmeal .078 Lettuce .425 Flour, entire wheat .037 Vegetable marrow .320 Flour, fine .028 Watercress .259 Macaroni, vermicelli .028 Beans, dried .215 Bread .021 Potatoes .160 Rice .012 Peas, dried .137 Cornmeal .009 Rutabaga (swedes) .103 Meat .002 Celery .094 Fruits: Carrots .077 Currants, dried .169 Parsnips .076 Peaches .150 Beans, fresh string .073 Blackberries .099 Spinach Rhubarb .064 .060 Raspberries Strawberries .072 .057 Cabbage .058 Bilberries .045 Onions .040 Currants .046 Asparagus .038 Oranges .043 Pumpkins .032 Huckleberries .037 Cucumber Radishes .028 .025 Grapefruit Cherries .029 .026 Tomato .019 Plums .022 Beet root .019 Apricots .021 Basal Foods: Watermelons .018 Pears .018 Cheese 1.240 Grapes .014 Pearl barley .250 Apples .011 Milk .172 Pineapple .008 IMPORTANT ORGANIC AND INORGANIC DIET CONSTITUENTS 323 Amounts of Calcium in Dried Food Materials GRAMS OF GRAMS OF cal- CALCIUM CIUM PER 100 PER 100 GM. GM. Potatoes 0.8 Cherries 7.5 Rice 0.8 Pears 7.9 Flour 1.02 Lemon juice 7.9 Tea 1.2 Beans 8.6 Wheat flour 2.2 Nut kernels 8.6 Cocoa 2.8 Radishes 8.8 Beef 2.9 Kohlrabi 10.2 Oatmeal 3.0 Gooseberries 12.2 Barley 3.5 Bananas 12.5 Coffee 3.6 White cabbage 12.6 Apples 4.0 Albumin of hens' eggs 13.0 Plums 4.9 Spinach 13.1 Lentils 5.1 Strawberries 14.2 Peas 5.1 Asparagus 15.9 Carrots 5.6 Cauliflower 21.7 Cornmeal 6.3 Grapes 36.9 Buckwheat 6.6 Yolk of egg 38.0 Cucumbers 6.9 Cow's milk 151.0 Foods with Calcium Content Estimated as CaO Dairy products 35 to 8%-Cheese, milk, egg yolks, eggs. Fruits 30 to 7%-Citron, oranges, pineapples, figs, pears, cherries, olives. Vegetables 27 to 5%-Savoy cabbage, cauliflower, onions, lettuce, radishes, celery, cabbage, en- dive, spinach, asparagus, carrots, kohlrabi, turnips, rhubarb, artichokes, pumpkin, lentils, cucumbers, toma- toes, beans. Meat and fish 18 to 7%-Oysters, salmon, pickerel, pork. Berries 14 to 8%-Strawberries, gooseberries, currants, huckleberries. Nuts 9 to 8%-Almonds, walnuts. Cereals 8 to 7%-Oatmeal, cornmeal, wheat flour. Even in very "hard" water the amount of calcium supplied is very small in relation to the amount required. About 1 to 1.5 gm. calcium intake is required per day. References: Bulletin, U. S. Department Agriculture; Dept. Chem. Exp. Station No. 45 and No. 185. Von Bunge, G.: Ztschr. f. Biol., 1904, (N.F. 45), xxvii, 532. Hoobler, B. P.: Arch. Pediat., 1912, xxix, 208. 324 METHODS IN MEDICINE Dietetic Treatment of Edema Synopsis of the Karell Cure.-Diet.-(Sometimes of service in edematous cases, and especially in cardiac disease.) Milk.-Two hundred c.c. at 8 a.m., 12 m., 4 p.m., and 8 p.m. The milk may be raw or boiled, warm or cold, to suit the taste. No other liquid should be given. If thirst is severe, patient may be allowed to rinse out mouth with water, but not to swallow it. If hunger is urgent, a small piece of toast or zwieback may be given with each portion of milk. The diet may usually be increased at the end of a week, by giv- ing a soft boiled egg (without salt or pepper) at 10 a.m. and a piece of zwieback at 6 p.m. The next day, an egg may be given at 10 a.m. and at 2 p.m. with a piece of white bread. From this time on, the diet may be gradually increased. It should, however, be kept poor in salt and poor in protein also, if the case is a cardio- renal one. No more than 800 c.c. of fluid should be taken for from two to four weeks after the disappearance of the edema. The cure should be carried out in bed and the bowels should be kept open (if necessary with cathartics which require no water in their administration.) Indications.-Cardiac, nephritic and hepatic dropsy, but espe- cially cardiorenal cases with edema from cardiac failure. Contraindications.-Impending uremia. Because of the low fluid intake, its use in this type of case has been followed by very bad results. Routine Observations on Patients Taking This Diet.-Chart daily total amount of urine, total chlorides, albumin, and blood pressure daily at same hour. Patient should be weighed daily, if possible. Size of heart and character of pidse are to be carefully watched. Prognostic Value.-The persistence of edema, stationary urine output or a diminution of the same, and particularly a failure of chloride output to increase, have been considered to indicate a bad prognosis. Drugs.-Digitalis, caffeine, morphine, etc., should be given only when absolutely necessary and should be discontinued as soon as possible. Rote.-1000 c.c. milk-P. 33 gm., F. 40 gm., CH. 50 gm. If a IMPORTANT ORGANIC AND INORGANIC DIET CONSTITUENTS 325 piece of toast is added to each feeding (200 gm. bread) P. 18, F. 2.6, CH. 105 must be added. Each egg added to the diet adds P. 6.7, F. 5.2, CH. 0. This diet is too high in protein and too low in CH. It is useful for cardiacs whose renal function is really not greatly impaired. Modifications of Karell diet.- (a) Water or fruit juice 1000 c.c. Potato, 1 kg. (cooked without salt) taken during the day in five portions. (b) Water or fruit juice 1000 c.c. Banana, 1 kg. (without salt) taken during the day in five portions. (c) Milk 800 c.c. to 1250 c.c. Bread 200 grams. Butter (without salt). Eggs, 2 or 3 References: Karell, Philippe: Arch. Gen. de Med., 1866, ser. vi, p. 513. Isenschmid. R.: Schwiezerische med. Aschenschrift, Basal. May 13, 1920, 50, No. 20. Jour. Am. Med. Assn., Ixxv, 173. (Abstract). Synopsis of the Epstein Cure.-Diet.-(Sometimes of service in edematous cases, and especially in nephrosis and cardiac disease.) The method consists in the administration of large quantities of properly selected proteins with a minimum of carbohydrates and the exclusion of fats. Calories 1280-2500. Food values: Protein 120 to 240 grams. Fats (unavoidable) 20 to 40 grams. Carbohydrates 150 to 300 grams. Articles Used.-Lean veal, lean ham, whites of eggs, oysters, gel- atin, lima beans, lentils, split peas, green peas, mushrooms, rice, oatmeal, bananas, skimmed milk, coffee, tea and cocoa. Fluids allowed as restricted to the quantity present in the food plus that which is necessary for the comfort of the individual patient amounting usually to 1200 to 1500 c.c. Salt.-Amount allowed is the quantity sufficient to make the food palatable. Reference: Epstein, A. A.: Am. Jour. Med. Sc., Nov., 1917, clii, 638, ibid, Feb., 1922, clxii. CHAPTER XXII PRINCIPLES GOVERNING THE DIET IN NEPHRITIS As Outlined in the Metabolism Unit by Dr. W. H. Olmsted The work of the kidney consists in excreting certain waste prod- ucts of the body. The weights of these products on an average diet of say 120 gm. of protein in 24 hours are: *Urea 32. gm. Chlorides 14.0 *Creatinin 1.8 " 2.0 *Uric Acid 0.7 " 2.6 * Ammonia 0.7 " Pot. Oxide 3.0 *Hippuric Acid 9.8 " Mg. and Ca. 0.9 Residue 2.2 " Residue 0.2 47.2 ~22?7 Total solids 70 gm. in 24 hours. Of these solids, the ones checked are concerned with the metab- olism of protein and if the nitrogen of the urine can be lowered, certainly the work of the kidney can be greatly decreased. Principles Involved in Decreasing the Urinary Nitrogen 1. During starvation the average urinary nitrogen for the average man will amount to 7 to 10 gm. in 24 hours. The ordinary nitrogen excretion on a diet of a 100 gm. protein will be 16 gm. Starvation in itself will reduce the work of the kidney. 2. But it is well known that the urinary nitrogen may be re- duced well below the starvation level by the feeding of carbo- hydrate in excess. This principle is known as the "protein sparing property of carbohydrate." The urinary starvation nitrogen may be cut in half by forcing carbohydrates. 3. The end products of carbohydrate metabolism are C02 and water, both of which are excreted, the one wholly, the latter par- tially, through the lungs. The lungs and the skin normally elimi- *These quantities of solids are excreted in an average fluid output of 1200 c.c. 326 PRINCIPLES GOVERNING THE DIET IN NEPHRITIS 327 nate fully as much water as the kidneys. These facts show that a high carbohydrate diet does not increase the work of the kidney, and that the mere elimination of nitrogen from the diet is not sufficient. 4. Is there any difference in the quality of nitrogen in different foods? One of the commonest fallacies current among practitioners is the idea that the protein of "white" meat or protein from milk or that from fish may be eaten by nephritic patients without as High Nephritic Diet Protein-50 grams No salt in food or on tray Weight in grams FOOD BREAK- FAST NOON NIGHT PROTEIN FAT CARBO- HYDRATE CALORIES Prunes 150 3.1 5.2 109.9 Egg 50 6.7 5.2 Bread 50 4.6 .6 26.3 Butter 10 8.5 Sugar 20 20. Cream 50 1.2 16. 2.2 Corn Flakes 25 1.4 .4 20.2 Potato (corn) 150 3.3 .1 27. Butter 10 8.55 Cream 25 Butter 10 8.5 Cream 25 .6 5. 1.1 Cabbage or (cauliflower 100 11.6 .4 4.4 ( Spinach (Celery Lettuce 20 .2 .4 Oil 10 10. Lemon 30 2.7 Pineapple 100 .4 .7 .4 Bread 50 2.9 20.2 Butter 15 12.7 Sugar 30 30. Rice 50 4. .1 39.4 Cream 25 4.4 Beans, string (tomato 100 (Aspara- gus (Cucum- 1. ber Onion 5 Grapefruit or 100 6. Strawberries 75 Bread 50 2.9 20.2 Sugar 20 20. Egg white 100 12.2 20. 49.5 81.9 387.4 2450.0 328 METHODS IN MEDICINE much harm as when the protein is in the form of "red" meat. It seems unnecessary to point out that 80 per cent of urinary nitro- gen is urea and that urea is formed irrespective of the kind of protein eaten. Quantity of protein is the point of importance, whatever its source. 5. Water.-The injured kidney in many cases is unable to ex- crete as concentrated a urine as a normal kidney. Thus to elimi- nate the same amount of solid matter as the normal kidney does in a 24-hour volume of say 500 c.c., the injured kidney must excrete those solids in a larger volume; this is often manifested by the increased volume of night urine. The normal kidney ex- cretes a concentrated urine of small volume at night, the injured kidney cannot do this, but eliminates the waste products in a larger volume often resulting in nocturia. These facts show the necessity of an adequate water intake in nephritis. Some cases through the diuresis tests can be shown to eliminate more waste products and that in this way an active forcing of water does good. In edema where a large amount of water is apparently already Medium Nephritic Diet Protein-35 grams No salt in food or on trays Weight in grams FOOD BREAK- FAST DINNER SUPPER TOTALS PRO- TEIN FAT CARBO. CAL. . Bread 20 20 20 60 5.4 .9 31.5 Butter 20 20 20 60 51. Corn Flakes or Post Toasties 20 20 1.1 .3 15.1 Cream 25 25 .5 4 .9 Sugar 20 15 20 55 55. Steak (lean) 75 75 14.7 9.6 Tomato or 100 Asparagus, or 100 100 Spinach or 100 100 Eggplant lob 100 Lettuce 20 20 .2 .4 Peaches 100 100 .7 .1 10.8 Egg 50 50 6.4 5.6 Grapefruit or 100 100 6. Strawberries or 75 75 Cabbage or 50 50 Okra 100 100 .8 .1 3.2 Celery 100 100 Rice 40 40 3.2 .1 19.2 Pineapple 170 100 270 1. 1.7 98.3 35.4 75.7 240.9 1786.5 329 PRINCIPLES GOVERNING THE DIET IN NEPHRITIS available the water intake should not be reduced unless the edema is of cardiac origin. Nephritic edema seems to respond often to forced fluids by active diuresis, apparently the result of an upset of the abnormal salt and water retention metabolism. Salt.-To reduce the work of the kidney the sodium chloride intake should be controlled. There are two methods of control: (a) Elimination of all extra salt that may be added voluntarily to food by the patient, and, (b) Feeding only salt-free foods, that is, adding no salt during processes of cooking or of manufacture of foods. To what degree salt should be restricted depends upon the severity of the case and the presence of edema. Following these principles the following diets are recommended: Low Nephritic Diet Protein-20 grams No salt in food or on tray Weight in grams FOOD BREAK- FAST DINNER SUPPER TOTAL PRO- TEIN FAT CARBO- HYDRATE CALO- RIES Bread 20 15 20 55 4.1 .8 26.7 Butter 20 20 20 60 51.0 Sugar 15 15 15 45 45. Cream 25 25 5 4. .9 Corn flakes or Post Toasties 20 20 1.1 .3 15.1 Tomato or 100 100 1.2 .2 3.5 Asparagus 100 100 Spinach 100 100 Eggplant 100 100 Peaches 100 100 7 1.1 10.8 Lettuce 20 20 2. .4 Egg 50 50 6.2 5.2 Grapefruit 100 100 6. Strawberries 75 75 Cabbage or 50 50 8 .1 2.2 Okra 100 100 Celery 100 100 St. Beans 100 100 Rice 40 40 3.2 .1 19.2 Cornstarch pud- ding Cornstarch 8 8 16 14.4 Butter 5 5 10 8.5 Lemon juice 50 50 100 9.8 Sugar 16 16 32 32. Pineapple 100 100 200 8 1.4 72.8 18.8 71.7 258.8 1839.7 330 METHODS IN MEDICINE Foods to Be Abstained From.- All forms of meat, this includes light and dark meat: fish, poultry, sausage, etc. All forms of meat soups or meat pies or stews. Salt, pepper or condiments. Nuts, gelatin, chocolate in any form. Cocoa. Any pastry made of eggs or containing eggs. Foods to Be Limited.- Corn meal; oatmeal; rice. Anything made of white flour such as any form of bread including toast or any form of pastry; shredded wheat; farina; macaroni; crackers; eggs and milk, peas and beans. Foods Unlimited.- All fruits: Apples, pears, peaches, bananas, cherries, grapes, oranges, grape fruit, lemons. Cornstarch. All vegetables except peas and beans. Sugar, candy, jellies, marmalades and honey. Ice cream (no eggs or gelatin). Low Protein-High Caloric Diet Weight in grams Food 8 A. M. 12 M. 6 P. M. Total PRO- TEIN FAT CARBO. CAL. Oatmeal 10 10 1.6 7. 6.6 Prunes 100 100 2.1 73.3 Toast 20 20 20 60 5.4 .7 31.5 Cream 1 for dal 1 200 5.0 40.0 9.0 Butter 1 for dal 100 1.0 85.0 Sugar 58 5.8 Cabbage 100 100 1.6 .3 4.5 Lettuce 20 20 .2 .4 Potato 150 150 3.3 27.0 Peaches 150 150 1. 16.2 Cornstarch 15 15 13.5 Lemon juice 50 50 4.9 Orange juice 50 50 .4 .1 5.8 Sweet potato 200 200 3.6 .4 52.2 Honey 25 25 1.1 20. Pineapple 200 200 .8 1.4 72.8 Raisins 30 30 .7 .9 22.8 Celery 100 100 1.1 .1 3.3 Flour 5 5 .5 .0 3.7 Tapioca 15 15 .2 .1 13.2 Lemon juice 50 50 4.9 Tomato (fresh) 100 100 .9 .4 3.3 30.5 130.1 44.69 2930.5 PRINCIPLES GOVERNING THE DIET IN NEPHRITIS 331 Dried fruits: raisins, figs, dates, prunes, apricots. Cream, butter, olive oil, olives. High Nephritic Diet.-Protein 50 gm., 2300 calories. Breakfast.- Fruit: One of the following: Prunes 150 gm.; 2 oranges; 1 grape fruit; 2 apples; 1 peach or 2 peaches; 1 banana; apricots. Eggs: one. Bread: 1 slice, butter 1 sq. Corn flakes. Cream and sugar in coffee. Jelly or marmalade. Pancakes (?) No egg. TAin ch.- Vegetables: One of the following: Potato (Irish or sweet), large; corn (canned or fresh), large helping. Salad: Made of any vegetables except peas, beans or nuts. Salad dressing of oil, no egg. Bread: two slices; butter (as desired) 2 squares. Cream and sugar in tea or coffee. Dessert: Pineapple, slice; honey; tapioca pud- ding, no egg; raisins; figs; dates (one of these). Dinner.- Egg, one. Vegetables: Any one except peas and beans. Rice or macaroni, one large helping. Bread: Two slices, butter 1 square. Corn starch pudding; any fruit; ice cream, no egg with any fruit dressing; candy. Cream and sugar. See Diet Lists on pages 327, 328, 329, and 330, for High Protein 50 gm., Medium 35 gm., Low 20 gm., and Low Protein-High Caloric Diets. Reference: Olmsted, Wm. II. (Director of the Metabolism Unit) Personal Communication. 332 METHODS IN MEDICINE PETER BENT BRIGHAM HOSPITAL A Practical Nephritic Diet O 'Hare and Wickers Any combination of the foods listed below may be selected. Foods not listed below must not be taken under any circumstances. In Group I the quantity of each is not restricted, although discretion is to be used. These foods are practically protein free. In Groups II and III there is a restriction in the total amount. The foods in these groups must be served in full or half portions. A full portion in Group II counts 1, equivalent to approximately 4 grams of protein. A full portion in Group III counts 2, equivalent to approximately 8 grams of protein. Points on recipes to count as indicated. B YOUR TOTAL SCORE FOR THE DAY SHOULD BE YOUR TOTAL AMOUNT OF FLUID SHOULD BEPINTS. Do not add salt or spices to the food after it has been cooked. Group I (No Restriction.) VEGETABLES FRUIT MISCELLANEOUS Asparagus String beans Apple Orange Sugar Cornstarch Cabbage Tomato Apricot Peaches Maple Sugar Arrowroot Carrots (fresh) Blueberries Pears Syrup Tapioca Cauliflower Tomato Cherries Pineapple Honey Post-Toasties Celery (cooked) Cranberries Plums Candy Butter Cucumbers Onions Grapefruit Prunes 4 dates per dayOlive Oil Lettuce Squash Grapes Raspberries 3 Sunshine arrowroot cookies Mushrooms Turnips Muskmelon Strawberries per day. Lemons Watermelon Group II (Each Full Portion Counts 1.) FULL PORTION VEGETABLES, ETC. FULL PORTION Bread (white) 1 av. slice Baked beans 1 tbsp. Bread (graham) 1 av. slice Lima beans 1% tbsp. Uneeda biscuit 5 crackers Potato, creamed 1 tbsp. Shredded Wheat 1 biscuit Potato, mashed tbsp. Graham crackers 5 crackers Potato, baked 1% med. Cereals, Etc. Potato, boiled med. Oatmeal Boiled rice Cornmeal mush Cream of Wheat 2 tbsp. 3 tbsp. 4 tbsp. 6 tbsp. Canned corn Green peas Beets Spinach 2% tbsp. 2 tbsp. 5 tbsp. 4 tbsp Farina 6 tbsp Bananas 2 large Macaroni 414 tbsp. Cream, heavy % cup 333 PRINCIPLES GOVERNING THE DIET IN NEPHRITIS (Each Full Portion Counts 2.) Group III FULL PORTION FISH FULL PORTION Milk 1 glass Cod, boiled 1" X 1" X 11/2" Egg 1 egg Haddock, boiled 1" X 1" x 11/2" Eggs (scrambled) iy2 tbsp. Halibut, boiled i"xi"xiy2" Flour, sifted % cup Mackerel, boiled 1" X 1" x 11/2" Meats Salmon, boiled 1" X 1" X 11/2" Lamb chop, broiled % chop Smelt y2" x i" x 3" Lamb, roast 3" x 2i/2" x 14" Oysters 7 oysters Beef, roast 3" x 2" x %" Crabmeat, canned 2 tbsp. Beef steak, broiled 2" x 1" x 1" Salmon, canned 1*4 tbsp. Chicken, roast 3" x 3" x i/8" Shrimp, canned 6 small VEGETABLE SOUP-0 Points 2 tbsp, onions, chopped. 2 tbsp, carrots, chopped. 2 tbsp, turnips, chopped. 3 tbsp, celery, chopped. 2 tbsp, butter. 1 pint water. Cook all the vegetables in butter for 3 minutes. Add the water and boil % hour or until vegetables are soft. CREAMED VEGETABLE SOUPS I Point 14 cup strained vegetables from Group III. % cup milk. Thicken with 1 or 2 tsp. cornstarch moistened in 1 tbsp, cold water. CUP CAKES-2 - 1 Point 3 tbsp, butter. Vi cup (scant) sugar. % egg. *4 cup milk. % cup flour. % tsp. vanilla. lr/2 tsp. baking powder. (Ryzon or Dr. Price's) Make into 6 cakes. SHORT CAKE-2=1 Point I14 cup sifted flour. 2 tbsp, lard or butter S. P. *4 cup (scant) milk. 2 tbsp, baking powder. Mix as biscuits and make into 8 biscuits. INDIVIDUAL PIE-1 Point % cup flour. tbsp. lard. % tsp. baking powder (Ryzon or Dr. Price's.) Ice water to make a. stiff dough. This pie may be made with any fruit from Group I for filling. Corn- starch instead of flour should be used for thickening. BLANCMANGE-1 Point tsp. cornstarch. % tbsp, sugar. 14 cup milk. 2 tbsp, cold water. %tsp. vanilla. Heat milk in double boiler, add corn- starch moistened in cold water and sugar. Cook until well thickened, add vanilla and chill. Fruit from Group III may be added. BAVARIAN CREAM-Points 1 1 tsp. granulated gelatin. 1% tbsp, cold water. % cup cream, whipped. 1 tsp. lemon juice. 2 tsp. sugar. % canned peach chopped fine. % cup boiling water. Soak gelatine in cold water, dissolve it in boiling water; add lemon juice and sugar and chill until it is the con- sistency of heavy molasses. Stir in peach pulp or other fruit from Group III; fold in whipped cream. Chill. 334 METHODS IN MEDICINE BAKED CUSTARD-2 Points % cup milk. ¥2 egg. % tbsp, sugar. Flavor with caramel or vanilla. Beat egg slightly; add milk and other ingredients. Pour into mold and bake in moderate oven with mold standing in pan of 'water. NOTE: This custard may be steamed or boiled. RICE PUDDING-2 Points hi cup boiled rice. hi cup milk. ¥2 egg. 2 tsp. sugar. 2 tsp. raisins. To the slightly beaten egg, add milk and other ingredients. Bake in mod- erate oven until lightly browned. TAPIOCA CREAM-1 Point hi cup milk. 1 tbsp, (scant) tapioca soaked over- night in 3 tbsp, cold water. hi tsp. vanilla. ¥3 egg. 1 tbsp, sugar. Drain tapioca, mix with sugar and add slowly to milk scalding in double boiler. Cook till tapioca is clear. Stir in gradually the beaten % egg yolk; fold in lightly the beaten white. PINEAPPLE MOUSSE-1/2 Point cup cream, heavy. 1% tbsp, shredded pineapple. % tsp. lemon juice. 1 tbsp, sugar. Whip cream, then fold in other in- gredients, previously mixed. Pour into mold, cover, and pack in 3 parts ice to 1 part salt, for 1% hours or until frozen through. ICE CREAM-1 Point % cup cream flavored as desired with fruit from Group III and sugar. WATER ICE-0 Points Any combination of fruit from Group III sweetened and frozen. NEPHRITIC DRESSING-0 Points (As used on salad, does not count any points) 1 egg y°ik. 1% cups salad oil. 4 or 5 tsp. lemon juice. 1 tsp. sugar. Beat the egg yolk, add 1 or 2 drops of lemon juice. Then drop by drop beat in the salad oil. Thin down with the lemon juice, adding only part of it at a time. Add sugar last. Reference: O 'Hare, J. P. and Wickers, M. C.: Personal communication. CHAPTER XXIII THE TREATMENT OF DIABETES MELLITUS The basal caloric requirements for a maintenance diet are ap- proximately 30 calories per kilogram of body weight per day. To maintain nitrogen equilibrium the body of an adult requires % of a gram of protein per kilo per day. Fat may be used at a rate of 2.5 grams per kilo per day. Carbohydrates are added to make up the total caloric value required. The proteins yield 4 calories, the fats 9 calories and the carbohydrates 4 calories per gram. The ketogenic antiketogenic balance may be calculated with Woodyatt's formula considering 90 per cent of the fat plus 46 per cent of the protein as ketogenic and 100 per cent of the carbohydrate plus 58 per cent of the protein, plus 10 per cent of the fat as antiketogenic. This F.A.-G. ratio may be from 1.5 to 2.5. For moderate work the patient needs 50 per cent more calories than when at rest. Metabolism Unit Observation Diet Weight in Grams 8 A. M. 12 M. 5 P. M. TOTAL ORDER PRO- TEIN 100 FAT 100 CARBO. 60 CAL. Bacon 25 25 2.4 16.8 Egg 100 100 13.4 10.5 Orange juice 100 100 .8 .2 11.6 Butter 8 10 28 .3 23.8 Cream 20 20 20 60 1.5 12 2.7 Steak 100 100 19.7 12.7 Ham 50 50 8.1 19.4 Cottage cheese 75 75 15.6 .7 3.2 Lettuce 25 25 .3 .5 Asparagus, canned 50 50 .7 1.1 Brussels sprouts 100 100 4.7 1.1 4.3 Peas, canned 125 125 4.5 .2 10.7 String beans, canned 100 100 1.1 .1 3.3 Apples 100 100 .4 .5 13 Consomme 150 150 300 6.6 Egg white 50 50-9A.M. 50 150 18.4 .3 Tomato 75 75 150 1.8 .3 5.2 Lemon juice 9 P.M. 50 50 4.9 SUMMARY 100.3 98.6 60.5 Butter 2. 1.7 1530.6 335 336 METHODS IN MEDICINE Low Fat Diet 8 A. M. 12 M. 6 P. M. ORDER PROTEIN 50 FAT 10 CARBO. 20 cal. Cantaloupe 100 100 .6 7.2 Egg 50 50 6.7 5.2 Butter 5 5 4.2 Egg white 40 50 90 11 .1 Consomme 250 250 500 10.8 Asparagus a.p.* 100 100 1.5 .1 2.3 Tomatoes 100 100 1.2 .2 3.5 Okra 75 75 7 3 Cottage cheese 25 25 5.2 1 Gelatin 10 10 9.1 String beans a.p. 100 100 1.1 .1 3.3 Spinach a.p. 100 100 2.1 .3 2.3 Lettuce 20 20 40 .4 8 50.4 10.2 Total 376.2 *a.p.=as purchased. Starvation Diet-Green Days Weights in grams FOOD 8 A. M. 12 M. 6 P. M. TOTAL PROTEIN FAT CARBO. CAL,20 Tomato (c) 100 100 1.2 .2 3.5 Celery 100 100 1.1 .1 3.3 Lettuce 25 25 50 .6 .1 1.1 Tomato (f) 50 50 100 .9 .4 3.3 Cauliflower 100 100 1.8 .5 3.7 String beans 100 100 1.1 .1 3.3 Asparagus 100 100 1.5 .1 2.4 8.2 1.5 20.5 128.3 20 Asparagus 100 100 1.5 .5 2.3 Tomato (c) 50 50 .6 .1 1.7 Lettuce 25 25 50 .6 .1 1.1 Tomato (f) 50 50 100 .9 .4 3.3 Celery (raw) 35 35 .3 1.1 Cabbage 100 100 1.6 .3 4.5 String beans 100 100 1.1 .1 3.3 Cauliflower 75 75 1.3 .3 2.7 7.9 1.4 20.0 124.2 Bran Bread Bran, 1 cup or 50 gm. Agar Agar, 2 teaspoonfuls or 5 gm. Cold Water, 14 glass or 70 c.c. Saccharin, gr. Salt. Tie bran in double cheesecloth bag and wash under cold water faucet until water is clear. Mix agar agar and water and bring to boil. 337 TREATMENT OF DIABETES MELLITUS Mix the agar agar mixture while hot with washed bran. Turn the mixture into a tray and press into a firm even sheet about % inch thick. Mark into squares. Allow mixture to stand until firm and cold, 6 to 8 hours and bake in moderate oven until dry, about one hour. Thrice Cooked Vegetables Clean thoroughly and cut into small pieces. Tie up loosely in large squares of cheesecloth, large enough to allow the vegetables to swell. Place in pan large enough to allow sufficient water to cover well, allow to boil for 15 minutes. Pour off the boiling water and place in cold water. Boil for 15 minutes. Pour off water as before and boil again for 15 minutes. Cheesecloth may be bought at any department store for about 5 cents per yard. What Carbohydrate Tables to Use All patients on diet of carbohydrate 30 or less: Use only vegetables of Table I (5%). Page 340. (Except orange, lemon and grapefruit juice). Patients on diet of carbohydrate 30-50 gm. Use only Tables I and II. Pages 340 and 341. Patients on diet of 50 to 100 gm. carbohydrate Use Tables I, II, III. Pages 340 and 341. Patients on diet above 100 gm. carbohydrate use all the carbohy- drate tables: except the pure sugars; that is, sugar, honey, molas- ses, candy or cooked or prepared foods having sugar in them, as preserved and canned fruits. In the calculation of a protein low diet (50 gm. or below) the pro- tein of vegetables from Table I should not be considered. The carbohydrate of "thrice cooked" vegetables in Table I should be considered as 1 per cent. Weights of Average Servings in Grams The weights in this table are very rough estimates and are shown only to give some slight idea of the value of the ordinary sources of measurement as used at the table. 338 METHODS IN MEDICINE Table A GMS. oz. String beans, cooked; 1 tablespoon 65-75 Tomato, raw, average, Cabbage, cooked; 75-100 1 tablespoon 50-75 Table B Peas, cooked; Apple, average size: 1 tablespoonful 55-65 l%-2 100-150 3 -5 Lemon juice, average c.c. in one lemon 20-30 Orange " " C ( Cl ( ( (c 55-65 l%-2 Grapefruit juice ' ' " " V? grapefruit 120-140 21/2-3 Peach average size 75-100 Table C Corn, cooked, average 1 tablespoon 75-85 Potato, mashed, cooked, 1 tablespoon 70-80 " raw average size 100-125 3 -4 Banana-raw-average size 150-175 5 -6 Table D Oatmeal: dry, one serving of cooked 15 % Bread: average slice 40-50 Cracker, soda 7-9 % Cracker, graham 9-12 TjVBLE E Protein and Fat Bacon, 2 slices, cooked 90-120 Meat, beef, mutton, lamb Average portion (100 gm. per day) 75-100 21/.-31/, Egg, average of edible portion 40 1% Egg, average of yolk 15.20 !<-% Egg, average of white 25-30 1 Gelatin dry: one cooked serving 3-5 Butter, one average square 10 339 TREATMENT OF DIABETES MELLITUS Axioms for the Diabetic It isn't the kind of food that is important but the quantity of starch and sugar consumed in 24 hours regardless of the kinds of food it appears in. Test your urine every night in a white spoon as faithfully as you go to bed or eat your supper. Don't worry about gaining weight. Remember an imperfect fur- nace cannot be expected to heat as efficiently as a perfect one. Bread is your most treacherous enemy. All diabetic breads, so- called, are not any better than ordinary white bread. Chief Carbohydrate Foods List Two 1/20 to 1/7 weight starch Asparagus Beans, string Brussels sprouts Cabbage Cauliflower Celery Cucumbers Lettuce Eggplant Okra Pumpkins Radishes Pickles, soui' Sauerkraut Spinach Tomatoes Beets 9 Carrots 8 Mushrooms 6 Onions 9 Parsnips 11 Peas 15 Squash 7 Turnips 7 Catsup 12 Olives green 9 Apples 13 Blackberries 8 Lemon juice 10 Pears fresh 11 Oranges 12 Peaches fresh 6 Grapefruit 6 Strawberries 6 Watermelon 7 Cantaloupe 7 Peaches canned 11 List Two 1/20 to 1/7 weight starch Beans lima 20 Corn, green 19 Potatoes 18 Baked Beans 17 Bananas 21 Cherries 17 Grapes 15 Pears Canned 18 List Three 1/7 to 1/4 weight starch List Four 1/4 to 1/2 weight starch Potatoes, sweet 26 Pineapple, canned Chocolate 30 Cocoa 37, 38 36 List Five 1/2 to 3/4-. weight starch Cornmeal 74 Oatmeal 57 Rice 79 Farina 76 Shredded wheat 76 White flour 75 Corn Flakes 81 Macaroni 74 Hominy 79 Bread all kinds 53 Crackers, soda 73 Tapioca 88 Honey 81 Sago 78 Sugar 100 B'ates 78 Cornstarch 90 Jelly and marma- Figs 74 Raisins 76 lade 85 ♦Numbers indicate approximate percentage. 340 METHODS IN MEDICINE Table I Carbohydrates 5 Per Cent or Less PRO- TEIN' EAT CARBO- HYDRATES WATER CAL. PER 100 GM. Vegetables: fresh Asparagus, as purchased 1.8 .2 2.5 94.0 29. Beans, string 2.3 .3 5.5 89.2 33.9 Brussels sprouts 4.7 1.1 4.3 45.9 Cabbage 1.6 .3 4.5 91.5 27.1 Cauliflower, a.p.* 1.8 .5 3.7 92.3 26.5 Celery 1.1 .1 3.3 94.5 18.5 Cucumbers .8 .2 2.4 95.4 14.6 Eggplant 1.2 .3 4.3 92.9 24.7 Lettuce 1.2' .3 2.2 94.7 16.3 Okra 1.6 .2 4.0 80.2 24.2 Pumpkins 1.0 .1 4.0 93.1 20.9 Radishes 1.3 .1 5.1 91.8 26.5 Rhubarb .6 .7 2.5 94.4 18.7 Sauerkraut, a.p. 1.7 .5 3.8 88.8 26.5 Spinach, a.p. 2.1 .3 2.3 92.3 20.3 Tomatoes, a.p. .9 .4 3.3 94.3 20.4 Vegetables, canned Asparagus, a.p. 1.5 .1 2.3 94.4 16.1 Brussels sprouts 1.5 0.1 3.4 19.6 Beans, string, a.p. 1.1 .1 3.3 93.7 18.5 Okra .7 .1 2.9 94.4 15.3 Tomatoes, a.p. 1.2 .2 3.5 94.0 19.7 Pickles, Condiments, etc: Olives, ripe, a.p. 1.4 21. 3.5 52.4 208.6 Pickles, cucumber, a.p. .5 .3 2.7 92.9 14.5 Consomme 2.2 8.8 Dairy Products: (special orders) Milk, whole, a.p. 3.3 4.0 5.0 87.0 69.2 Buttermilk 3.0 .5 4.8 91.0 35.7 *a.p.=as purchased. 341 TREATMENT OF DIABETES MELLITUS Table II Carbohydrates 5 to 15 Per Cent PRO- TEIN FAT CARBO- HYDRATES WATER CALO- RIES Vegetables, fresh Beets 1.6 .1 8.6 87.5 41.7 Carrots 1.1 .4 8.2 88.2 40.8 Mushrooms, a.p. 3.5 .4 6.0 88.1 41.6 Onions 1.6 .3 9.1 87.6 45.5 Parsnips 1.6 .5 11.0 83.0 54.9 Peas, green 7.0 .5 15.2 74.6 93.3 Squash 1.4 .5 7.2 88.3 58.9 Turnips 1.3 .2 6.8 89.6 34.2 Vegetables, canned Beans, lima, a.p. 4.0 .3 13.4 79.5 72.3 Peas, green, a.p. 3.6 .2 8.6 85.3 50.6 Pickles, condiments, etc: Catsup, tomato, a.p. 1.5 .2 12.3 82.8 57 Olives, green, a.p. .8 20.2 8.5 42.3 219 Fruits, berries, etc, fresh: Apples .4 .5 13. 84.6 58.1 Blackberries, a.p. 1.3 1.0 8.4 86.3 47.8 Lemon juice 9.8 39.2 Oranges .8 .2 11.6 86.9 51.4 Peaches .7 .1 5.8 89.4 26.9 Grapefruit 6.0 24 Pears .6 .5 11.4 84.4 52.5 Strawberries 1.0 .6 6.0 90.4 33.4 Watermelon .4 .2 6.7 92.4 30.2 Cantaloupe .6 7.2 31.2 Fruits, etc., canned: Peaches, a.p. .7 .1 10.8 88.1 46.9 a.p.=as purchased. Table III Carbohydrates 15 to 25 Per Cent PRO- TEIN FAT CARBO- HYDRATES WATER CALO- RIES Vegetables: Beans, lima, green 7.1 .7 20.3 68.5 115.9 Corn, green 3.1 1.1 19.2 75.4 93.6 Potatoes, raw 2.2 .1 18.0 78.3 80.8 Vegetables, canned: Beans, baked, a.p. 6.9 2.5 17.1 68.9 118.5 Corn, green, a.p. 2.8 1.2 18.2 76.9 94.8 Fruits, Berries, etc., fresh Bananas yellow 1.3 .6 21.0 75.3 94.6 Cherries 1.0 .8 16.5 80.0 77.2 Grapes 1.3 1.6 14.9 77.4 76.2 Fruits, berries, etc., canned; Pears, a.p. .3 .3 18.0 81.1 75.9 a.p. = as purchased. 342 METHODS IN MEDICINE Table IV Carbohydrates 15 to 40 Per Cent PRO- TEIN FAT CARBO- HYDRATES WATER CALO- RIES Vegetables: Potatoes sweet, raw 1.8 .1 26.1 69.0 117.9 Fruits, etc, canned: Pineapple, a.p. .4 .7 36.4 61.8 153.5 Miscellaneous: Chocolate, a.p. 12.9 48.7 30.3 5.9 611.1 Cocoa, a.p. 21.6 28.9 37.7 4.6 497.3 Baker's cocoa 23.0 25.2 48.2 511.6 Hershey's 22.6 26.1 41.5 491.3 a.p.=as purchased. Table V PRO- TEIN FAT CARBO- HYDRATES WATER CALO- RIES Flours, meals, etc Com meal 9.2 1.9 74.0 12.5 332.8 Oatmeal 16.1 7.2 66.6 7.3 395.6 Rice 8.0 .3 78.8 12.3 349.9 Flour, wheat 11.4 1.0 74.8 12.0 349.9 Wheat-Farina 11.0 1.4 75.9 10.9 360.2 Corn Flakes 5.5 1.5 81.0 359.5 Wheat-Shredded 10.5 1.4 76.2 8.1 359.4 Macaroni 13.4 .9 74.1 10.3 358.1 Hominy 8.3 .6 28.1 11.8 151.0 Bread, crackers and pastry: Bread, brown, a.p. 5.4 1.8 47.1 43.6 226.2 Rolls, plain a.p. 9.7 4.2 59.6 25.2 315.0 White bread, all analysis, a.p. 9.2 1.3 52.6 35.3 258.9 Zwieback, a.p. 9.8 9.9 73.5 5.8 422.3 Graham crackers, a.p. 10.0 9.4 72.3 5.4 413.8 Soda crackers, a.p. 9.8 9.1 72.8 5.9 412.3 Sugars, starches, etc: Tapioca .4 .1 88.0 11.4 354.5 Honey, a.p. .4 .0 81.2 18.2 326.4 Sago 9.0 .4 78.1 12.2 352.0 Sugar Granulated .0 .0 100.0 400.0 Cornstarch .0 .0 90.0 360 Fruits, etc., dried: Dates 2.1 2.8 78.4 15.4 347.2 Figs, a.p. 4.3 .3 74.2 18.8 316.7 Raisins 2.6 3.3 76.1 14.6 344.5 Prunes dried 2.1 73.3 22.3 301.6 Fruits, etc., canned: Figs, stewed, a.p. 1.2 0.3 40.9 56.5 171.1 Marmalade (orange peel) a.p. .6 .1 84.5 14.5 341.3 a.p.=as purchased. Carbohydrates 40 Per Cent and Above TREATMENT OF DIABETES MELLITUS 343 Table VI Vegetable Equivalents Brussels Sprouts 100-Grams Asparagus (c) 187 Grams Carbohydrate 4.3 - Cauliflower 116 - String beans 135 - Tomato 125 - Celery 133 - Spinach 187 - Cabbage 95 Cabbage 100- Asparagus 199 Carbohydrate 4.5 - Cauliflower 122 - Spinach 199 - String Beans 138 - Celery 138 - Tomato 138 - Brussels Sprouts 105 Cauliflower, 100- Celery 113 Carbohydrate 3.7 - Lettuce 168 - Tomato (c) 106 - String Beans (c) 113 - Brussels Sprouts 86 - Spinach 161 - Asparagus (c) 161 - Cabbage 84 Celery 100- Cauliflower 89 Carbohydrate 3.3 - Asparagus (c) 143 St. Beans (c) 100- Tomato (c) 94 Carbohydrate 3.3 - String Beans (c) 100 - Lettuce 150 - Brussels Sprouts 76 - Spinach 143 - Cabbage 75 Asparagus (c) 100- Cauliflower 62 Carbohydrate 2.3 - Tomato (c) 65 Spinach (f) 100- String Beans (c) 69 Carbohydrate 2.3 - Brussels Sprouts 55 Lettuce 100- Celery 69 Carbohydrate 2.3 - Cabbage 52 344 METHODS IN MEDICINE Protein 15 Per Cent or Less Table VII PRO- TEIN FAT CARBO- HYDRATES WATER CALO- RIES Beef, corned and pickled: Beef, corned 15.6 26.2 53.6 298.2 Tongue pickled Fresh fish: 12.8 20.5 62.3 232.5 Flounder 14.2 .6 62.2 Mackerel, entrails removed, a.p. 11.6 3.5 43,7 107.9 Red snapper Shellfish, etc., fresh: 10.6 .3 45.1 Oysters, solids, a.p. Shellfish, etc., canned: 6.0 1.3 3.3 83.3 48.9 Oysters, a.p. Eggs: Hen's uncooked 8.8 2.4 3.9 83.4 81.4 13.4 10.5 75.7 148.1 Hen's cooked 13.2 12.0 73.2 160.8 Hen's, egg white, boiled or raw 12.3 .2 86.2 51.0 Hen's, yolks, boiled or raw 15.7 33.3 49.5 362.5 a.p.=as purchased. Table VIII Protein 15 to 25 Per Cent PRO- TEIN FAT CARBO- HYDRATES WATER CALO- RIES Beef, fresh Loin, lean 19.7 12.7 67.0 193.1 Bound, lean 21.3 7.9 70.0 156.3 Ribs, edible portion 17.5 26.6 309.4 Beef, corned and pickled: Corned, all analysis 15.6 26.2 53.6 298.2 Lamb, fresh: Leg, hind, medium fat 19.2 16.5 63.9 225.3 Loin, chop 18.7 28.3 53.1 329.5 Mutton fresh: Loin, chop Leg, hind, lean 16.0 33.1 50.2 361.9 19.8 12.4 67.4 190.8 Poultry and game, fresh: 74.8 108.5 Chicken, broilers 21.5 2.5 Fowls 19.3 16.3 63.7 223.9 Turkey 21.1 22.9 55.5 290.5 Fish, fresh: Halibut steaks or sections 18.6 5.2 75.4 121.2 Trout, brook, whole 19.2 2.1 77.8 95.7 Cod Haddock 16.5 17.2 .4 .3 64.1 69.6 71.5 Shad 18.8 9.5 70.6 160.7 Fish, preserved and canned: Mackerel, salt, entrails removed 42.2 289.6 21.1 22.8 Salmon, canned 21.8 12.1 63.5 196.1 Dairy products, etc: 4.3 72.0 109.8 Cheese, cottage, a.p. 20.9 1.0 Cheese, Neufchatel, a.p. 18.7 27.4 1.5 50.0 327.4 Cheese, Roquefort, a.p. 22.6 29.5 1.8 39.3 363.1 a.p.=;as purchased. TREATMENT OF DIABETES MELL1TUS 345 Table IX Protein 25 Per Cent And Above PRO- TEIN 30.0 27.3 36.9 28.6 27.6 91.4 FAT CARBO- HYDRATES WATER CALO- RIES Beef, dried, etc: Dried, salted and smoked Dish preserved and canned: Cod, salt "boneless" Herring, smoked Dairy products, etc.: Cheese, American pale a.p. Cheese, Swiss, a.p. Miscellaneous: Gelatin, a.p. 6.8 .3 15.8 35.9 34.9 .1 .4 0.3 1.3 54.3 55.0 34.6 31.6 31.4 13.6 182.8 111.9 289.8 438.7 429.7 370.4 a.p.=as purchased. Table X PRO- TEIN FAT CARBO- HYDRATES WATER CALO- RIES Pork, fresh Loin, (ehops) (medium fat) 16.6 30.1 52.0 337.3 Pork, pickled, salted and smoked: Ham, smoked, medium fat 16.3 38.8 40.3 414.4 Bacon, smoked, medium fat 9.9 67.4 18.8 646.2 Dairy products, etc: Butter, a.p. 1.0 85.0 11.0 769.0 Cream 2.5 20.0 4.5 74.0 208.0 Nuts: Almonds 21.0 54.9 15.3 4.8 639.3 Brazil nuts 8.6 33.7 3.5 2.6 351.7 Filberts 15.6 65.3 13.0 3.7 702.1 Hickory nuts 15.4 67.4 11.4 3.7 703.8 Peanuts 25.8 38.6 21.9 9.2 538.2 Pecans unpolished 9.6 70.5 15.3 2.7 734.1 Walnuts, California 18.4 64.4 11.6 2.5 699.6 Walnuts, California (Soft shell) Olive Oil 16.6 63.4 100.0 13.5 2.5 691.0 900.0 a.p.=as purchased. Fats 346 METHODS IN MEDICINE Low Fat-High Protein Table XI PRO- TEIN FAT CARBO- HYDRATES WATER CALO- RIES Gelatin 91.4 .1 .0 13.6 366.5 Cod fish (boneless) 27.3 .3 .0 55.0 111.9 Cottage cheese 20.9 1.0 4.3 72.0 109.8 Trout 19.2 2.1 .0 77.8 95.7 Red snapper 10.6 0.3 .0 43.7 45.1 Spring chicken (broilers) 21.5 2.5 .0 74.8 108.5 Egg white 12.3 0.2 .0 86.2 51.0 Liver 20.4 4.5 1.7 71.2 128.9 Halibut 18.6 5.2 .0 75.4 121.4 Dried beef 30.0 6.5 0.4 180.1 Round beef 21.3 7.9 .0 70.0 156.3 Reference: Olmsted, Wm. H.: (Director of the Metabolism Unit) Jour. Biol. Chem., Jan., 1920, xli, 45. Diabetic Treatment (Principles of Dr. Elliott P. Joslin, Boston) Fasting;-Fast until sugar free. Drink water freely and tea, coffee and clear meat broth as desired. In very severe long stand- ing and complicated cases, without otherwise changing habits or diet, omit fat, after two days omit protein and halve carbohydrate daily to 10 grams, then fast. Carbohydrate Tolerance.-When the 24-hour urine is sugar free add 150 grams of 5 per cent vegetables and continue to add 5 grams carbohydrates daily up to 20 and then 5 grams every other day, passing successively upward through the 5, 10 and 15 per cent vegetables, 5 and 10 per cent fruits, potato and oatmeal to bread, unless sugar appears or the tolerance reaches 3 grams carbohydrate per kilogram body weight. Protein Tolerance.-When the urine has been sugar free for two days, add 20 grams protein (3 eggs) and thereafter 15 grams protein daily in the form of meat, until the patient is receiving 1 gram protein per kilogram body weight, or if the carbohydrate tolerance is zero, only % gram per kilogram body weight. Fat Tolerance.-While testing the protein tolerance, a small quan- tity of fat is included in the eggs and meat given. Add no more fat until the protein tolerance is below this figure then add 25 grams daily until the patient ceases to lose weight or receives not over 40 calories per kilogram body weight. TREATMENT OF DIABETES MELL1TUS 347 Reappearance of Sugar.-This return of sugar demands fasting for 24 hours or until sugar free. The diet is then decreased twice as rapidly as before, but the carbohydrates should not exceed half the former tolerance until the urine has been sugar free for two weeks, and it should not then be increased more than five grams per week. Weekly Fast Days.-Whenever the tolerance is less than 20 grams carbohydrate, fasting should be practiced one day in seven; when the tolerance is between 20 and 50 grams carbohydrate, upon the weekly fast day 5 per cent vegetables are added as well. If the tolerance is more than 100 grams carbohydrate, upon weekly fast days, the carbohydrate should be halved. Diabetic Treatment (Joslin) CARBOHYDRATES GRAMS PROTEIN GRAMS FATS GRAMS CALORIES 5 20 (3 eggs) 20 10 120 15 35 200 20 50 280 20 ■80 340 25 80 420 25 80 25 645 30 80 50 890 30 80 75 1115 35 80 100 1380 35 80 125 1605 40 80 150 1830 40 80 175 2055 45 80 200 2300 8 A. M. 12 M. 6 P. M. ORDER PROTEIN 0 FAT 0 CARBO. 40 CAL. Grapefruit Pears canned Cabbage thrice cooked Celery Tapioca Sugar 100 100 100 100 12 3 100 100 100 100 12 3 0.3 6 3.18 1 1 11 3 .3 3.40 163.9 Protein and Fat Free Diet 348 METHODS IN MEDICINE DIETS WITH WHICH TO BE- COME SUGAR FREE Carbohydrate Protein Fat Calories 5 per cent Vegetable Orange Oatmeal Shredded Wheat Uneeda Potato Bread bD bfl a Cream 20% fat Bacon Butter Meat Fish Skimmed Milk Name of diet T. D. 1 189 89 15 1247 300 300 ... 1 ... 240 90 ... ... 90 120 480 1 T. D. 2 102 58 0 640 300 300 1 ... 120 180 300 2 T. D. 3 64 33 0 388 300 300 ... ... ... 60 90 240 3 T. D. 4 36 27 0 252 300 200 90 120 4 T. D. 5 15 5 0 80 300 50 5 MAINTENANCE DIETS CARBOHYDRATE (C) PROTEIN AND FAT (PF) Cl PF1 10 11 6 138 300 . . . . ... 1 1 C2 PF2 22 13 18 302 300 100 1 60 ... 2 C3 PF3 32 24 24 440 600 100 ... 2 60 3 C4 PF4 42 29 39 635 600 200 2 60 30 . . . 4 C5 PF5 52 32 53 813 600 200 15 2 60 30 15 5 C6 PF6 63 43 65 1009 600 200 30 2 90 30 15 30 6 C7 PF7 73 51 70 1126 600 300 30 2 90 30 15 60 7 C8 PF8 83 59 87 1351 600 300 30 2 2 90 30 30 90 8 C9 PF9 96 62 93 1409 600 300 30 % 2 2 120 30 30 90 9 CIO PF10 107 63 93 1517 600 300 30 1 2 2 120 30 30 90 10 Cll PF11 131 75 98 1706 600 300 30 1 2 120 2 120 30 30 120 11 C12 PF12 155 79 98 1818 600 300 30 1 2 240 2 120 30 30 120 12 FOOD WEIGHT IN IRAMS APPROXIMATE EQUIVALENT FOOD WEIGHT IN GRAMS APPROXIMATE EQUIVALENT Orange ...300 1%( Large size) Bread ... .! 10 ... slices 5 per cent vegetables . ...300 3 Moderate portions Oatmeal (dry wgt) 30 . . . .... Skimmed milk . ...480 1 pint (16 ounces) Cream ... .... 60 . . . .... . .4 tablespoonfuls Fish ...120 2 small portions Bacon . . . 10 . .. .... strips Potato ...240 2 medium-sized potatoes Butter ... .... 10 . .. Meat ....90 1 moderate portion 'From the 3x5 card of Dr. Elliott P. Josl n printed aS Form 4 by Thomas Groom & Co. Inc., 105 State St. Boston, Massachusetts. Diabetic Test and Maintenance Diets* DIET IN GRAMS TEST DIETS TREATMENT OF DIABETES MELLITUS 349 Water, clear broths, coffee, tea, cocoa shells and cracked cocoa can be taken without allowance for food content. Foods Arranged Approximately According to Content of Carbohydrates* 5% 10% | 15% 20% * Recko ii average carbohydrate in 5% veg. as 3%-of 10% veg. as 6% l%-3% 3%-5% 10% 15% 20% nd Lettuce Tomatoes String beans Green Peas Potatoes i Cucumbers Brussels Pumpkin Artichokes Shell beans Spinach sprouts Turnip Parsnips Baked beans Asparagus Water cress Kohl-rabi Canned Lima Green corn o Rhubarb Sea Kale Squash beans Boiled rice ■<Z) Endive Okra Beets Boiled maca- Q Marrow Cauliflower Carrots roni Sorrel Eggplant Onions GQ Sauerkraut Cabbage Green peas s Beet greens Radishes canned Dandelion Leeks greens String beans Watermelon Raspberries Plums Eh K Swiss chard canned Strawberries Currants Bananas 0 Celery Broccoli Lemons Apricots Prunes H Mushrooms Artichokes Cranberries Pears canned Peaches Apples CO Pineapple Huckleberries H Ripe Olives (20% fat) Blackberries Blueberries & Grapefruit Gooseberries Cherries Oranges 1 kilogram - 2.2 pounds. 1 gram protein, 4 calories 30 grams gm. or cubic centimeters 1 ' ' carbohydrate, 4 " c.c . = 1 ounce. 1 ' ' fat, 9 ' ' A patient ' ' at rest ' ' requires 25 calo- 6.25 " protein contain 1 gm nitrogen ries per kilogram. (30 grams 1 oz.) Carbohydrates Protein Fat Calories CONTAIN APPROXIMATELY gin. gm. gm. Oatmeal, dry weight 20. . . 2 118 Shredded Wheat 23. .. 3 0 104 Cream, 40% . . . 1 1 12 116 Cream, 20% . . . 1. . . 1 h .62 Milk 1.5 1 1 19 Brazil nuts 2. . . 5 20 208 Oysters, six .. . . 4 6 1 4 Meat (uncooked, lean) 0. .. 6 .3 . .5 Meat (cooked, lean) 0 8 o 77 Chicken (cooked, lean) 0 8 3 59 Bacon 0. . . 5 15 155 Cheese 0. . . 8 11 131 Egg (one) . .. • 0 6 6 78 Vegetables 5% group 1. . . 0.5 .... 0 . .6 Vegetables 10% group 2 0.5 0 10 Potato 6 1 0 28 Bread • • • • 18. . . 0 .84 Butter 0 0 25 225 Oil 0. . . 0 30 270 Fish, cod, haddock (cooked) . . . 0. . . 6 . 0 .24 Broth 0 0.7 0 3 Fruit 10% 3. . . 0 .0 .12 ♦From 3x5 card of Dr. Elliott P. Joslin, Thomas Groom & Co., Boston, Mass. 350 METHODS IN MEDICINE Higher Caloric Values in Diabetic Diets Obtained by the Use of a High Percentage of Fats Menus Arranged According to the Principles of Drs. L. H. Newburgh and P. L. Marsh by Miss Dorothy Stewart, Special Dietitian, University of Michigan Hospital, Ann Arbor. DIABETIC DIET FAT PROTEIN CARBOHYDRATES CALORIES No. 1 85 gm. 18 to 22 gm. 12 to 15 gm. 800 to 1000 No. 2 145 gm. 25 to 30 gm. 18 to 22 gm. 1200 to 1600 No. 3 165 gm. 30 to 35 gm. 25 to 30 gm. 1600 to 2000 No. 4 185 gm. 50 to 60 gm. 30 to 40 gm. 2000 to 2500 Diabetic Diet No. 1. Example 1. 18-22 Protein 12-15 Carbohydrate 800-1000 Calories FOOD WT. GM. PRO. GM. FAT GM. CARBO. GM. CALORIE s Dinner Fish 50 8.9 5.1 82. with butter 10 .1 8.5 77. Cabbage 50 .8 .1 2.8 16. with Mayonnaise .7 38.2 353. Tomatoes Broth-Tea Supper 100 1.2 .2 4.0 23. String beans 80 1.8 .2 5.9 33. with bacon Spinach Soup 10 1.0 6.5 62. Spinach 10 .2 4.0 .3 2. Cream Broth to fill bowl 10 .2 .3 38. Celery Broth-Tea Breakfast 20 .2 .7 4. Omelet 1 Egg G.7 5.2 74. with butter Coffee 10 .1 8.5 77. 21.9 76.5 14.0 84.2 TREATMENT OF DIABETES MELLITUS 351 PRO. GM. FAT GM. CARBO. GM. CALORIE.-5 Dinner Cottage Cheese, 1 oz. 5.92 0.28 1.21 31.1 Lettuce, 2 oz. 0.68 0.18 1.62 10.8 with mayonnaise, 1 oz. 20.04 191.4 Tomatoes, 3 oz. 1.02 0.18 3.39 19.2 with butter, % oz. 0.1 8.5 Broth Tea Supper • Cabbage, iy2 oz. 0.67 0.13 2.38 46.6 with mayonaise, 1% oz. 28.35 255.1 (oil 1 oz.) Spinach, 4 oz. 2.36 0.36 3.64 27.2 with butter, % oz. 0.14 12.4 108.9 Broth Tea Breakfast 1 egg 6.03 4.72 66.6 with butter, % oz. 0.1 8.5 76.9 Cream, 1% oz. (18%) Broth 1.2 8.4 2.1 88.8 Tea Totals 18.22 91.68 14.34 999.5 Diabetic Diet No. 1. Example 2 Diabetic Diet No. 2. Example 1 PRO. GM. FAT GM. CARBO. GM. CALORIE S Dinner Chicken, 2 oz. 12.2 1.42 61.6 with butter, 1 oz. 0.28 24.09 217.9 Beets, 3 oz. 1.35 0.09 8.25 39.3 with butter, % oz. 0.14 12.04 108.9 String beans, 3 oz. with ground bacon, %oz. 1.95 0.27 6.3 35.4 1.49 9.18 88.6 Broth Tea Supper Lettuce Salad: Shredded lettuce, 2 oz. 0.68 0.18 1.64 10.8 Chopped onion, % oz. 0.22 0.04 1.04 6.9 Mayonnaise, 2 oz. (oil, % oz.) Tomatoe bisque: 42.53 82.6 Tomatoes, 1 oz. 1 bouillon cube 0.34 0.06 1.13 6.4 Cream, (40%), 2 oz. Hot water to till bowl 1.24 22.68 1.7 215.8 Tea Breakfast Bacon, 1 oz. 2.98 18.37 115.7 Egg, 1 6.03 4.72 66.6 Cream (18%), 1 oz. for coffee Broth 0.8 5.6 1.4 59.2 Total 29.70 141.27 21.82 1,415.7 352 METHODS IN MEDICINE The Use of Insulin The details of Banting's epoch-making discovery have been suffi- ciently worked out that the extract is practically applicable. Insulin is the great boon for the case of diabetes mellitus with coma, severe acidosis, intercurrent infection, or complications, es- pecially those requiring surgical treatment under general anesthesia. The use of the extract is also justifiable in juvenile cases and those Diabetic Diet No. 2. Example 2 25-30 Protein 18-22 Carbohydrate .200-1600 calories FOOD WT. GM. PRO. GM. FAT GM. CARBO. GM. CALORIES Dinner Pork chops 60 10.0 18.0 202. Cabbage 100 .2 .3 5.6 32. use pork drippings Spinach 100 2.1 .3 3.2 24. with butter Broth-Tea Supper Asparagus Salad 20 .2 17.0 154. Lettuce 10 .1 .3 2. Asparagus 80 1.2 .1 2.1 13. Mayonnaise 50 .7 38.8 338. Tomatoes 100 1.2 .2 4.0 23. with butter Nut Charlotte 10 .1 8.5 77. Walnuts chopped 10 1.8 6.4 1.3 70. Cream 50 1.1 20.0 1.5 190. Broth-Tea Breakfast Bacon with 20 2.1 13.0 125. 1 egg Coffee with 6.7 5.2 74. Cream 30 .7 12.0 .9 114. 28.2 139.8 18.9 1438. less severe eases where the patient must be allowed a good caloric intake to be able to carry on his work. Insulin administration only supplements the dietary management of diabetes mellitus. Instead of superseding diet methods it makes them all the more necessary and in a way even more rigid. Before starting insulin treatment, in a case of moderate severity, the patient's carbohydrate tolerance should be established. He should preferably be desugarized in the ordinary way by low TREATMENT OF DIABETES MELL1TUS 353 caloric diets. He must be taught food values and the technics of the Benedict and the Gerhardt tests. When, after desugarization and step-up dietary additions, sugar appears in the urine or if after several days of the undernutrition diet the patient excretes sugar, insulin should be given. The dosage may be calculated at the rate of one unit of insulin for each 2 to Diabetic Diet No. 3. Example 1 FOOD WT. GM. PRO. GM. FAT GM. CARBO. M CALORIES Dinner Boiled Ham Spinach salad 60 12.2 13.4 169. Lettuce 10 .1 .3 2. Spinach 100 2.0 .3 3.2 24. Lemon 10 .6 3. Mayonnaise 50 .8 38.8 353. Olives 23 .2 4.6 1.9 50. Onions 100 1.6 .3 9.9 49. with Cream 30 .7 12.0 .9 114. with butter Broth-Tea Supper Vegetable soup 10 .1 8.5 77. Tomato j Brown in 10 .1 .4 2. Celery ( butter, add 5 .2 1. Carrot / broth and cook 10 .1 .9 5. Onion ' till tender 5 .5 2. Butter 20 .2 17.0 154. Broth 1 Cup String beans 150gm. 1.6 .2 4.5 31. with butter Orange jelly 30 .3 25.5 231. Orange juice 10 1.1 4. Gelatin with 5 4.6 18. Whipped Cream 20 .4 8.0 .6 76. Broth-Tea Breakfast Bacon with 20 2.1 13.0 125. 1 Egg Coffee with 6.7 5.3 74. Cream 30 .7 12.0 .9 114. Totals 34.5 158.9 I 25.9 1678. 3 grams of glucose excreted during the preceding 24 hours. The total number of units should be divided between two doses. The dosage is carefully increased until the urine is sugar-free. When sugar-free, the diet is increased by the addition of 5 to 10 grams of carbohydrate and 10 to 20 grams of fat. If sugar appears after the addition, the urine is made sugar-free by cau- 354 METHODS IN MEDICINE tiously increasing the dose of insulin. When sugar-free again, or if no sugar appears after two or three days, another similar addition to the diet is made and the same studies made. The diet is thus stepped up to a working level; that is, 45 to 50 calories per kilo- gram (2.2 pounds) of body weight. Diabetic Diet No. 3. Example 2 1 30-35 Protein 25-30 Carbohydrate 600-2000 calories FOOD WT. GM. PRO. GM. FAT GM. CARBO. GM. CALORIES Dinner Beef tenderloins 80 13.0 19.5 227. with butter 10 .1 8.5 77. Asparagus 100 1.5 .1 2.8 18. with butter 10 .1 8.5 77. Squash 100 1.4 .5 9.0 46. with butter 10 .1 8.5 77. Broth-Tea Supper String bean salad Lettuce 10 .1 .3 2. String beans 50 1.1 .1 3.7 26. Pimento 10 .2 .4 2. Onion 10 .2 1.0 5. Mayonnaise 30 .5 23.3 228. Tomatoes 120 1.4 .2 4.8 28. with butter 20 .2 17.0 154. Chocolate Pudding Cream 100 2.2 40.0 3.0 381. Cocoa 2 tsp. 1 .2 .3 .4 5. Broth-Tea Breakfast Bacon with 30 3.2 19.4 187. 1 Egg 6.7 5.3 74. Coffee with Cream 30 .7 12.0 .9 114. 32.9 163.2 26.3 1728. Insulin may be injected subcutaneously a half hour before each meal, the dose preceding each meal depending upon the amount of carbohydrate in the meal. Olmsted and Kahn have successfully limited the insulin injections to one per day by concentrating two- thirds of the total carbohydrate in the 12 o'clock or noon meal and dividing the other third between breakfast and supper. The total insulin for the 24 hours is injected subcutaneously one and one- half (1%) hours before the heavy carbohydrate meal. Concentrated TREATMENT OF DIABETES MELLITUS 355 FOOD WT. GM. PRO. GM. FAT GM. CARBO. GM. CALORIES Dinner Pork Chops 80 13.3 24.0 268. Kraut (use drippings) 100 1.6 .3 5.6 32. Carrots 100 1.1 .4 9.3 45. with butter 20 .2 17.0 154. Broth and Chicken Fat 10 .1 8.5 77. Tea Supper Asparagus Salad Lettuce 20 .2 .1 .6 4. Asparagus 80 .9 .1 2.2 14. Pimento 10 .2 .4 2. Mayonnaise 50 .7 38.8 4.5 353. String beans 150 1.6 .1 31. with butter 20 .2 17.0 154. Junket (Milk) 100 3.3 4.0 5.0 69. with whipped cream 20 .4 8.0- 1.2 76. Broth and Ch. Fat 10 .1 8.5 77. Tea Breakfast Bacon 30 3.2 19.4 187. 1 Egg Broth and Ch. Fat 10 6.7 .1 5.2 8.5 74. 77. Coffee with Cream 30 .7 12.0 .9 114. Totals 34.4 171.8 28.9 1803. Diabetic Diet No. 3. Example 3 Diabetic Diet No. 3. Example 4 FOOD WT. GM. PRO. GM. FAT GM. CARBO. GM. CALORIES Dinner Roast beef (in fat) 50 8.3 13.3 154. Beets with 100 1.6 .1 9.7 46. butter 25 .2 21.2 192. Cabbage with 80 1.2 .2 4.6 26. Cream 30 .7 12.0 .9 114. Butter Broth Tea Supper Cabbage salad 10 .1 8.5 77. Cabbage 50 .8 .1 2.8 16. Pimento 10 .2 .4 2. Lettuce 20 .2 .1 .6 4. Mayonnaise 50 .7 38.8 353. String beans with 150 1.6 .2 4.5 31. Butter Custard 20 .2 17.0 154. 2 Egg Yolks 4.7 10.0 109. Cream 60 1.3 24.0 1.8 228. Broth Tea Breakfast Bacon 20 2.1 13.0 125. 1 Egg 6.7 5.2 74. Cream for Coffee Broth 30 .7 12.0 .9 114. Totals 31.8 175.7 26.2 1819. 356 METHODS IN MEDICINE solutions of insulin must be used and great care must be taken, by wiggling the needle around in the subcutaneous tissue, etc., so as not to inject the potent extract into a small vein. The patient is taught the exact technic of measuring out the dosage in a tuber- culin (Luer) syringe and injecting the extract aseptically. The patient must also be taught the symptoms of hypoglycemia, which may result from an overdose of the extract. The prodromal Diabetic Diet No. 4. Example 1 FOOD WT. GM. PRO. GM. FAT GM. CARBO. GM. CALORIES Dinner Pork chop 150 23.55 42.65 488.0 String beans 120 2.60 .36 8.40 47.2 with ground bacon 15 1.49 9.18 88.6 Beets 120 1.80 .12 H.66 42.4 with butter 30 .28 24.09 217.9 Cucumber pickles: 30 .23 .06 .88 4.9 Broth ... . . . ... Tea Supper Cabbage pancakes: Cabbage 90 1.35 .27 4.77 26.7 1 Egg 6.70 5.25 74.0 Butter (% for frying) 30 .28 24.09 217.9 Egg salad: Lettuce 15 .17 .04 .41 2.7 Deviled egg, 1 Cream dressing 6.70 5.25 74.0 30 1.22 10.73 .49 103.4 with mayonnaise 40 • • . 28.35 255.1 Grapefruit 50 .39 .10 5.04 23.0 Broth • • • Tea • .. Breakfast Bacon omelet: Ground bacon 10 1.05 6.48 62.5 1 Egg . .. 6.70 5.25 74.0 Butter 15 .14 12.04 108.9 Cream (40%) 30 .62 11.34 .85 107.9 Totals 55.27 185.65 31.84 2019.1 symptoms are headache, giddiness or dizziness, restlessness and numbness of the extremities. In the second stage the patient may be chilly or warm and may show sweating or pallor. In the third stage there is a sense of cold and trembling, a shaking chill with- out fever, muscular tremors, subnormal temperature, collapse and coma. One must always be on the lookout for these symptoms and combat them promptly by the administration of glucose, candy, sugar, corn syrup or the juice of an orange, any of which serve as TREATMENT OF DIABETES MELLITUS 357 an efficient antidote. The glucose antidote must at times be given by stomach tube or per rectum or intravenously. It is of distinct advantage to estimate the blood sugar level when insulin is being administered and especially when symptoms of in- sulin shock appear. Likewise, in acidosis, precomatose and coma- tose states the CO2 tension of the alveolar air by Marriott's method and the blood alkali percentage by Van Slyke's method should be Diabetic Diet No. i. 4. Example 2 FOOD WT. GM. PRO. GM. FAT GM. CARBO. GM. CALORIES Dinner Veal steak (roast) 100 19.9 10.8 177. Onions 126 1.9 .4 11.9 49. With Cream 50 1.1 20.0 1.5 190. Tomatoes 150 1.8 .3 6.0 35. with butter 30 .3 25.5 231. Fruit salad Lettuce 10 .1 .3 2. Celery 50 .6 1.6 9. Grapefruit 80 .6 .2 8.1 37. Whipped cream 30 .7 12.0 .9 114. Tea-Broth Supper Cream of Celery Soup 50 .6 1.6 9. Celery Cream Broth to fill bowl 75 1.6 30.0 2.2 285. Boiled ham Custard 30 6.1 6.7 85. 2 Egg yolks 4.7 10.0 109. Cream 90 2.0 36.0 2.7 343. Tea Breakfast Eggs, 2 13.4 10.5 148 with butter 30 .3 25.5 231. Coffee with cream 20 .4 8.0 .6 76. Broth 56.1 195.9 37.4 2130. estimated. In the absence of blood analyses the urine should be collected through an indwelling catheter and constantly watched for changes in its sugar and acetone body content. References: The Journal of Metabolic Research. "The Insulin Number." Olmsted, W. H., and Kahn, S. II.: Jour. Amer. Med. Assn., June 30, 1923, Ixxx, 1903. 358 METHODS IN MEDICINE Diabetic Diet No. 4. Example 3 FOOD WT. GM. PRO. GM. FAT GM. CARBO. GM. CALORIES Dinner Chicken 100 19.3 16.3 224. with butter 20 .2 17.0 153. Carrots 120 1.3 .5 11.2 54. with cream 50 1.1 20.0 1.5 195. Tomato jelly Lettuce 10 .1 .3 2. Tomatoes 100 1.2 .2 4.0 23. Gelatin 5 4.6 18. Shaved onion 5 .1 .5 2. Mayonnaise Plain junket 50 .8 38.8 353. Milk 100 3.3 4.0 5.0 69. with whipped cream 20 .4 8.0 .6 76. Broth-tea Supper Boiled ham Cream of spinach soup 30 6.1 6.7 85. Spinach (chopped) 20 .4 .1 .6 5. Cream 50 1.1 20.0 1.5 195. Butter Broth to fill bowl 5 4.3 38. Cabbage salad Cabbage 15 1.2 .2 4.2 24. Onion 10 .2 .3 1.0 5. Mayonnaise 50 .8 38.8 353. Broth-tea Breakfast Bacon with 30 3.2 19.4 189. Eggs 2 13.40 10.5 148. Cream with Coffee-broth 30 .7 12.0 .9 114. 59.5 217.1 31.3 2323. TREATMENT OF DIABETES MELL1TUS 359 FOOD WT. GM. PRO. GM. FAT GM. CARBO. GM. CALORIES Dinner Beef Tenderloin 100 16.2 24.4 284. with butter 20 .2 17.0 153. Celery 100 1.1 .1 3.3 19. with Cream 50 1.1 20.0 1.5 195. Beets 120 1.9 .1 11.5 48. with butter 20 .2 17.0 153. Nut Charlotte Cream (whipped) 60 1.3 24.0 1.8 229. Walnuts Saccharin and Vanilla 10 1.8 6.4 1.3 70. Broth-tea Supper Cabbage pancakes Ground cabbage 100 1.4 .2 4.8 27. Egg 6.7 5.3 74. Butter (y2 for frying) Egg salad 30 .3 25.5 231. Lettuce 15 .2 .4 3. Deviled egg (1) 6.7 5.3 74. Mayonnaise 25 .4 19.4 176. String beans 150 1.6 .2 4.5 31. with butter 20 .2 17.0 153. Sliced oranges Broth-tea Breakfast 70 .6 .1 8.1 36. Bacon with 20 2.1 1300 125. Eggs-2 Coffee with 13.4 10.5 148.0 Cream 30 .7 12.0 .9 114. 58.1 217.5 38.1 2343. Diabetic Diet No. 4. Example 4 360 METHODS IN MEDICINE Diabetic Diet No. i. 4. Example 5 FOOD WT. GM. PRO. GM. FAT GM. CARBO. GM. CALORIES Dinner Cottage Cheese 100 20.9 1.0 1.4 110. Pimento 20 .3 .9 5. Cream 50 1.1 20.0 1.5 195. Spinach Salad Lettuce 10 .1 .3 2. Spinach 100 2.1 .3 3.2 24. Hard Cooked Egg 1% 3.4 5.1 37. Mayonnaise 50 .8 38.8 353. Peas 100 3.6 .2 9.8 with butter 20 17.0 154. Celery 25 .3 .8 5. Broth-tea Supper Vegetable Salad Lettuce 10 .1 .3 2. Beets 50 .8 4.8 23. String beans 30 .3 .9 6. Cabbage 20 .3 1.6 6. Onion 10 9 1.0 5. French dressing Oil Paprika 20 20.0 180. Vinegar Salt and pepper Cream of Tomato Soup Tomatoes 50 .6 .1 2.0 10. Cream 75 1.6 30.0 2.2 285. Butter 10 .1 8.5 77. Broth to fill bowl Custard 90 Cream Egg Yolks 2 6.7 46.0 2.7 452. Broth-tea Breakfast Eggs 2 13.40 10.5 148. with butter 20 .2 17.0 154. Coffee Cream for coffee 30 .7 12.0 .9 114. 57.9 226.5 34.3 2402. 361 TREATMENT OF DIABETES MELLITUS Diabetic Diet No. 4. Example 6 FOOD AMT. PRO. GM. FAT. GM. CARBO. GM. CALORIES Dinner Roast chicken 100 gm. 19.30 16.30 224.0 Squash with 120 gm. 1.68 .60 10.80 55.2 butter 10 gm. .10 8.50 76.9 Head lettuce with Thousand Island dressing .72 .18 1.74 14.4 Mayonnaise 50 gm. .75 38.82 352.9 Pickles (chopped) 10 gm. .08 .02 .31 1.7 Pimento 10 gm. .16 .01 .45 2.7 Celery 60 gm. .66 .06 1.96 11.4 Olives 30 gm. .24 6.06 2.55 65.7 Ice cream 90 gm. 1.98 36.00 2.70 342.9 Coffee Supper Oyster stew: Oysters 30 gm. 1.80 .39 .99 14.7 Cream 90 gm. 1.98 36.00 2.70 342.9 Hot water to fill bowl Cabbage salad: Cabbage 50 gm. .80 .15 2.80 16.0 Onions 10 gm. .16 .03 .99 4.9 Pimento 10 gm. .16 .01 .45 2.5 Mayonnaise 50 gm. .75 38.82 352.9 Orange jelly 1 recipe 5.23 12.00 1.98 133.4 Tea Breakfast Grapefruit 50 gm. .39 .10 5.04 23.0 Bacon with two 2.62 16.20 156.2 eggs 25 gm. 13.40 10.50 148.0 Coffee with cream 30 gm. .66 12.00 .90 114.3 Broth Totals 53.62 232.75 36.36 2456.6 High fat recipes, compiled by Miss Dorothy M. Stewart. Baked Custard FOOD AMT. PRO. GM. FAT. GM. CARBO. GM. CALORIES Egg yolks, 2 Cream, 40% Vanilla Saccharin 3 gm. 70 gm. 4 drops 4.70 1.54 10.00 28.00 2.10 109.0 266.7 Totals 6.24 38.00 2.10 375.7 Beat egg yolks with fork, add cream, then saccharin dissolved in vanilla. Bake in a pan of water in a slow oven until knife will come out clean. 362 METHODS IN MEDICINE Nut Charlotte FOOD AMT. PRO. GM. FAT. GM. CARBO. GM. CALORIES Cream, 40% Walnuts Saccharin Vanilla 70 gm. 10 % gi'. 4 drops 1.54 1.84 28.00 6.44 2.10 1.30 266.7 70.3 Totals 3.38 34.44 3.40 337.0 Whip cream, add finely chopped nuts, then saccharin dissolved in vanilla. Orange Jelly FOOD AMT. PRO. GM. FAT. GM. CARBO. GM. CALORIES Gelatin 5 gm. 4.57 14.8 Cold Water 1 Tb. Boiling Water % c- Orange juice 10 gm. 1.08 4.3 Saccharin ¥2 gr- Cream, 40% 30 gm. 6.66 12.00 .90 114.3 Totals 5.23 12.00 1.98 133.4 Soak gelatin in cold water two minutes. Dissolve in boiling water. Add saccharin dissolved in orange juice. The cream may be served with the jelly or whipped and folded in when the jelly is partly stiff. Chocolate Pudding FOOD AMT. PRO. GM. FAT. GM. CARBO. GM. CALORIES Cream Cocoa, 14 tsp. Agar agar Vanilla Saccharin 100 gm. 1 gm. 1 tsp. % tsp. 2.20 .21 40.00 .28 3.00 .37 381.0 4.9 Totals 2.41 40.28 3.37 385.9 Mix cocoa with agar, add cream and steam in pan of hot water for 20 minutes. Add saccharin dissolved in vanilla and chill. Cream Dressing FOOD AMT. PRO. GM. FAT. GM. CARBO. GM. CALORIES Cream 350 gm. 7.70 140.00 10.50 1333.5 Egg yolks (8) 120 gm. 18.84 39.96 435.6 Salt, 1}£ tsp. Pepper, % tsp. > Mustard, 2 tsp. j Vinegar Butter 10 gm. 125 gm. 70 gm. .70 59.50 538.3 Totals 27.24 239.46 10.50 2307.4 Per 50 gm. 2.01 17.73 .77 170.9 Add scalded cream to beaten egg yolks and cook in a double boiler, stirring constantly until mixture forms a smooth coating on the spoon. Add melted butter, then seasonings mixed to a smooth paste with vinegar. TREATMENT OF DIABETES MELLITUS 363 Mayonnaise FOOD AMT. PRO. GM. FAT. GM. CARBO. GM. CALORIES Egg yolks, 6 U c. vinegar Oil, 1 qt. Mustard, 1 tb. ) Salt, 2 tb. • Paprika, tb. J 90 gm. 120 gm. 700 gm. 30 gm. 14.13 29.97 700.00 335.7 6300.0 Totals Per 50 gm. 940 gm. 14.13 .75 729.97 38.82 6635.7 352.9 Mix dry ingredients, add egg yolks and beat slightly. Add one half the vinegar and mix well. Add oil slowly, beating constantly until all is added. Thin if necessary with rest of vinegar. If dressing should curdle, take three egg yolks and add curdled mixture to them, slowly beating as though it were oil. Tomato Jelly FOOD AMT. PRO. GM. FAT. GM. CARBO. GM. CALORIES Tomatoes Gelatin Cold, water Salt, 14 Op- pepper, paprika and celery sail 100 gm. 5 gm. 1.20 4.57 .20 4.00 23.0 18.3 Totals 5.77 .20 4.00 41.3 Soak gelatin in cold water two minutes. Dissolve in boiling tomatoes, add seasoning and chill. Serve on lettuce with mayonnaise or cream dressing. Vegetable Soup FOOD AMT. PRO. GM. FAT. GM. CARBO. GM. CALORIES Celery 5 gm. .005 .15 1.0 Carrots 20 gm. .22 .08 1.86 9.0 Onions 5 gm. .80 .01 .49 2.4 Cabbage 5 gm. .08 .01 .28 1.6 Butter Broth 15 gm. .15 12.75 116.3 Totals 1.30 12.85 2.78 130.3 Chop vegetables finely and brown in butter. Add broth and simmer until tender. Season with salt and pepper. References: Newburgh, L. H., and Marsh, Phil L.: Arch. Int. Med., 1920, xxvi, 647. Newburgh, L. H., and Marsh, Phil L.: Arch. Int. Med., 1921, xxvii, 699. Stewart, Dorothy M.: The Modern Hospital, 1922, xviii, 164. 364 METHODS IN MEDICINE Dietary Instructions for Out Patient Diabetics By Miss Dorothy M. Stewart FOODS TO AVOID: Sugar, bread, cake, pie, flour-thickened gravies and sauces, potatoes, tapioca, macaroni, spaghetti, and milk. FOODS TO USE: Meats (preferably fat) fish, poultry, eggs, cheese. Vegetables 5 per cent (see list). Vegetables 10 per cent (see list). Cream-as heavy as possible. Butter. Mayonnaise or French dressing. 5 PEE CENT VEGETABLES: Tomatoes, celery, cucumbers, cabbage, aspara- gus, rhubarb, lettuce, endive, marrow, sorrel, sauerkraut, beet or dandelion greens, swiss chard, spinach, water cress, brussels sprouts, cauliflower, okra, egg plant, string beans, radishes. 10 FEE CENT VEGETABLES: Turnips, kohlrabi, squash, beets, carrots, onions, canned peas, mushrooms, pumpkin. Suggested Plan for Meals Breakfast Bacon, 2 slices 2 eggs Coffee with cream Dinner Meat, 1 small serving Vegetable 5 per cent (see list) with butter, cream or as a salad with dressing Vegetable 10 per cent (see list) with cream or butter ■ Supper Vegetable 5 per cent as a salad with dressing Vegetable 5 per cent with cream or butter A clear meat broth may be used with and be- tween meals if desired. Tea and coffee may also be used. Mayonnaise Dressing 2 egg yolks 1 tsp. mustard 1 tsp. salt % tsp. paprika 2 tb. vinegar 1% c. oil (Olive, Mazola, "7", or Wesson). Beat egg yolks slightly, add seasonings, stir until smooth, then add % the vinegar. Now add the oil very slowly, beating all the time and being sure it is all worked in before more is added. Thin, if necessary, with the rest of the vinegar. If it should curdle, take another egg yolk and add curdled mix- ture to it as though it were oil-slowly. French Dressing 15 gms. Oil (1 tb.) Count same as butter 1 tsp. vinegar Salt, pepper, and paprika Put all in cup and stir briskly with a fork. Pour over shredded cabbage, let- tuce or any vegetable salad. PART IV THERAPEUTIC METHODS CHAPTER XXIV GENERAL RULES The interne is directly responsible for the treatment of all pa- tients on his ward. He is to dictate all orders for therapeutic measures to the head nurse and see that the orders are correctly written, signed by himself, interpreted and carried out promptly and accurately. Suggestions as to therapeutic management of any case must be made to the interne. In an emergency, orders may be given verbally or over the tele- phone by the interne, but these must be recorded with the regular orders and signed as soon as possible. The orders must all be as clear and definite as possible with definite directions as to the preparation to be used, the dosage, the time and method of administration. Except for drugs given a specified time before or after regular meals (as t.i.d. 30 min. a.c. or t.i.d. 15 min. p.c.) the time is to be stated, at the hour, as 8 a.m. or 8 p.m. and not as "morning or evening." Pharmacologic or chemical names of drugs are to be used in orders instead of proprietary names, as for example: Acetyl salicylate for "Aspirin" Acetphenetiden for "Phenacetin" Phenyl salicylate for "Salol" Hexamethylenamine for "Urotropin" Arsphenamine for "Salvarsan" Theobromine sodium salicylate for "Diuretin," etc. Only U.S.P. and N.F. preparations are kept in stock in the drug room. Others as New and Non-Official Remedies must be ordered through the medical secretary, from the outside, until their value is proved and they are accepted. 365 366 METHODS IN MEDICINE The dosage is to be given in the international metric figures as, cubic centimeters, grams and milligrams. (See tables on dosage and transposition from English to Metric systems, p. 369.) All prescriptions of all classes must be written in the metric system and copied onto the current history sheets, dated and timed. If time of day is important, as it is in all serious conditions, the hour and fraction must be given. All prescriptions must be begun the day ordered unless the effect is wanted later. Emergency meas- ures must be begun within half hour. No symbols as simply "Rx" or "Rx, No. x" or "Special Rx" are to be recorded, but exact constituents and doses used in the pre- scriptions. Standing orders and the orders for all routine and special thera- peutic procedures must appear on the standard T.P.R. graphic chart. The standing orders including the general management as to rest, bath, diet, and drugs must be copied on each sheet while occasional orders are recorded in the space of the day on which they are given. The exact amount of the treatment and the exact time of adminis- tration must also appear in the space of the day on which it is given. The interne must record these procedures under Remarks on the front page of the history. Among the measures that require special attention as standing or special orders are hydro- and mechanotherapy, baths, baking and other hyperemic measures, massage, gymnastics, occupational therapy; open air, actino- or thermotherapy; x-rays or radium treatments; vaccines, serums, glandular preparations; or drug therapy, massive doses of digitalis tincture, or courses of diuretics as theocin; intravenous, intraspinal, or intramuscular injections; transfusion or bleeding. Eliminative measure, as sweat baths. Hy- podermoclysis, proctoclysis or fluid intraperitoneally or intrave- nously; gavage, gastric lavage, irrigation or any special clinic treat- ment in the 0. P. D. Diets for special types of diseases are given in section on Diets, which is to be consulted before orders for them are written. Diets are to be ordered by the interne after carefully ascertaining and considering the condition of the patient, and consulting, as soon as possible, the Director of the Metabolic Unit. This is especially required in the management of all diabetic and nephritic cases. Diabetic diets, and certain nephritic diets, are all prepared in the GENERAL RULES 367 special diet kitchen in the metabolism unit under the supervision of the director of the metabolism laboratory. All other special diets are prepared in the pavilion diet kitchen. Diabetic patients, when showing no signs of acidosis or any signs of severe diabetes on physical examination at admission, may be placed on the observation diet. If, however, there is hyperpnea and any suggestion of an acetone breath, fluids should be forced, and immediate steps taken to ascertain the patient's degree of acidosis, the alveolar CO2 vol. per cent, the blood CO2, and the amount of organic acids especially /?-oxybutyric and diacetic should be determined as soon as possible. The blood sugar level and the urinary sugar output are required in the further dietetic manage- ment of any case. Nephritic diets are to be selected after kidney function studies have been made. The blood nitrogen is to be determined as soon as the suspicion of nephritis arises, preferably immediately after admission. Then it is advisable to put the patient on especially low (20 gm. protein) nephritic diet. After general examination, 12 hour urine examinations, P.S.P. and N.P.N., the diet prescription is adjusted to the patient's condition. Hydrotherapy is to be ordered only after consultation with the director of the hydrotherapy department, so that the needs of the patient are best supplied and the director acquainted with the ex- act findings in the patient and the desires of the internist. Promptly Acting Powerful Drugs Drugs like adrenalin, nitroglycerin, etc., and all drugs given for prompt pharmacological effect should be administered under the observation of a member of the medical group or an interne, who should make and note the necessary observations. Orders for such drugs must state specifically for what indication the dose is to be repeated and furthermore the limit to which the repetition may be carried. Cathartics ordered at night to be given the next morning are not given if the patient's bowels move during the night, unless the order definitely states that this is to be done. 368 METHODS IN MEDICINE Narcotic Drugs Heroin is not to be used in this clinic under any circumstances. Codein is to be given only for definite reasons which the pre- scriber must state in the history. In place of this drug, paregoric or small doses of morphine are to be used. Narcotic drugs shall be ordered daily and not by standing order. As in the case of all drugs with powerful pharmacologic action, the order must state specifically for what indications the drug is to be administered, the shortest interval allowable between doses and the maximum number of repetitions permissible. Treatment Sheet While the patient is still under treatment, the "Therapeutic Re- sume" sheet should be begun. On this should be stated, concisely and in chronologic order: All the details in the therapeutic management of the case. The symptoms or conditions treated, with the results in each case: e.g., Peptic ulcer: type, location, gastric analyses, diet, antacid check test, treatment and results. Constipation: kind, degree, treatment, results. Diarrhea: Cause, details as to number and character of stools, treatment, results. Anemia: (full blood note), type, treatment, progress, results. Leukemia: (full blood note), type, treatment, progress, results. Meningitis: chief symptoms, organism, daily treatment with cell counts, etc., results. Heart disease: type, treatment, results. Kidney disease: type, treatment, results. Arthritis: type joints involved, foci treated, treatment, results. C.N.S. Lues: Symptoms, e.g., ataxia, spasm, cell count, Wasser- mann, treatment, results. Pain: place, cause, treatment, results. Insomnia: cause, treatment, results. "Nervousness": treatment, results. This "Therapeutic Resume" is to be filled out by each member of the senior group in Medicine for each of his cases, and checked by the interne. Note any other symptoms or other indications, treatment, results. GENERAL RULES 369 Table English-Metric Equivalents ACCURATE APPROXIMATE G. or Gm. Mg. or Mgm. 1 Grain = .0648 grams .065 < Grams 65 Milligrams ¥2 " .0324 4 4 .032 4 4 32 4 4 ¥ " .0216 4 4 .022 4 4 22 4 4 % " .0162 < 4 .016 4 4 16 4 4 % " .0108 c 4 .011 4 4 11 4 4 % " .0081 4 4 .008 4 4 8 4 4 V12 ' ' .0054 4 4 .005 4 4 5 4 4 V1G ' ' .0040 4 4 .004 4 4 4 4 4 ¥0 " .0032 4 c .003 4 4 3 4 4 ¥0 ' ' .00216 4 4 .002 4 4 2 4 4 ¥0 " .0013 44 .0013 4 4 1.3 4 4 %0 ' ' .00108 4 4 .001 4 4 1 4 4 ¥100 " .00064 4 4 .0006 4 4 .6 4 4 ¥.50 " .000432 4 4 .0004 4 4 .4 4 4 ¥00 " .00032 4 4 .0003 4 4 .3 4 4 ACCURATE APPROXIMATE 1 Dram - 3.88 Grams 4.00 Grams 1 Ounce - 31.10 Grams 30.00 Grams 1 Minim - 0.061 c.c. 0.06 c.c. 1 Fluidram - 3.69 c.c. 4.00 c.c. 1 Fluidounce - 29.57 c.c. 30.00 c.c. 0.001 Gram - %5 Grain 1/60 Grain 1.0 Gram - 15.43 Grain 15.00 Grain 1.0 c.c. - 16.23 min. 15 Min. Courtesy of A. D. Carr, M.D. CHAPTER XXV EMERGENCY MEASURES Intravenous Therapeutic Solutions The introduction of solutions directly into the venous circulation is common practice especially in some of the most urgent emer- gencies. The sterile towels, gauze, tubing, needles, glassware, in- cluding glass ground syringes, and the solutions ordinarily used should be kept in readiness in the emergency ward. Aseptic surgi- cal technic should be used in injecting solutions directly into the blood stream. The preparation of solutions for intravenous infusion is quite important and requires care. Normal Saline or Physiological Salt Solution 0.85 per cent.- Place exactly 8.5 grams of chemically pure sodium chloride in a 1000 e.c. flask and add exactly one liter of distilled water. Filter the solution through paper into a clean flask. Plug with gauze covered cotton plugs and autoclave for 20 minutes at 20 pounds of steam pressure. Alkali or Sodium Bicarbonate Solution 4 per cent.-See p. 394. Place 25 grams of chemically pure anhydrous sodium carbonate in a 1000 c.c. of freshly distilled water. The 2.5 per cent sodium carbonate solution is filtered through paper and about 5 drops of 1 per cent alcoholic solution of phenolphthalein indicator. Immerse an absorption tube (Folin) in the solution in the flask. With rubber tubing connect this to a calcium chloride drying tube filled with absorbent cotton. Plug the flask with gauze covered cotton plugs and autoclave the entire connected apparatus for 15 minutes at a steam pressure of just less than 20 pounds. Cool care- fully and then connect the drying tube with a carbon dioxide tank. Bubble the gas through until the pink alkaline solution just be- comes colorless indicating a Ph of between 8 and 9. This procedure carried to this endpoint converts the 2.5 per cent carbonate solu- tion to a 4 per cent bicarbonate solution. The absorption tube is then carefully removed and the sterile gauze plug replaced. 370 EMERGENCY MEASURES 371 Intravenous Sugar or Glucose Solution. 50 per cent Stock, 5 per cent Emergency.-Dissolve 500 grams of chemically pure glu- cose in 1000 c.c. of distilled water. Solution may be aided by heat. Filter through cloth, cotton and finally paper to remove all of the flocculent precipitate. This stock solution may then be placed in a clean flask, stoppered and autoclaved for 15 minutes at 20 pounds of steam pressure. Dilutions of the stock solutions are, however, usually made before the autoclaving. Transfer 100 c.c. of the stock 50 per cent solution to a little flask, make up to a 1000 c.c. with distilled water, plug and autoclave as above in preparing the routine emergency 5 per cent glucose solution. Intravenous Acacia or Hypertonic Gum-Glucose Solution. Er- langer and Gasser (Annals of Surgery, 1919, xlix, 389) advise the following method of preparation. Grind up and dissolve in 720 c.c. of hot freshly glass distilled water 250 grams of "extra select'' pearl form, gum acacia (gum arabic U.S.P.). Stir constantly to prevent gumming of the acacia into a very slowly dissolving mass. Add 180 grams of chemically pure glucose making a total amount of about 1000 c.c. The solution is filtered under pressure through a thick pad of glass wool, sealed in a high pressure flask and heated in an autoclave to a temperature of 120° C. for a few minutes and then filtered under pressure through an alundum filter dish of a porosity of R.A. 98. The solution is then filled in the largest tubes that would fit in the centrifuge cups at hand. Usually tubes of 100 c.c. capacity can be utilized while ones of 350 or 400 c.c. would be preferable. The solution should be run down the side of the tidDe carefully to pre- vent the formation of bubbles which would persist for some time in the viscid solution. The tube, when filled, is hermetically sealed and sterilized by heating to 120° C. in autoclave for exactly fifteen minutes. A slight flocculent precipitate which is apt to form dur- ing sterilization is thrown down firmly against the bottom of the tube by centrifuging the material for about an hour. This solution contains 25 per cent gum arabic in 18 per cent glucose, and is given in doses of 5 c.c. per kilo of body weight. Sodium Citrate 2 Per Cent Solution, Anticoagulant for Transfu- sion Blood.-Dissolve 10 grams of chemically pure sodium citrate crystals in 500 c.c. of freshly distilled water. This 2 per cent solu- tion of sodium citrate is usually perfectly clear, any sediment 372 METHODS IN MEDICINE should be removed by filtering through paper. The solution may be transferred in smaller volumes to smaller flasks or the stock flask itself may be retained. Plug with gauze covered cotton plugs and autoclave for 15 minutes at 2'0 pounds of steam pressure. Allow 10 c.c. of this solution for every 100 c.c. of blood making a 0.2 per cent concentration in the blood which is sufficient to pre- vent coagulation and still not a toxic amount. TREATMENT OF POISONINGS General Emergency Measures Get what information is-possible from the witnesses as to the type of poisoning and the approximate degree, the time of the poi- soning, the length of coma and the number of times the patient vomited. Note any odors, stains, burns or color changes on the patient. Examine the patient hastily, noting especially the reflexes and the breathing. If possible evacuate the patient's stomach with the use of the gagging reflex. Save vomitus for examination. In the absence of severe corrosions insert the stomach tube and lavage the stomach with one or two liters of milk or 50 per cent albumin water (half egg white, half water). Save washings for examination. Lavage should be continued with a few liters of warm 5 per cent sodium bicarbonate solution. In the case of oxalic acid poisoning the 5 per cent sodium bicar- bonate solution must be completely removed and a solution of cal- cium carbonate or lime water administered. In the case of alkali poisoning the 5 per cent sodium bicarbonate solution is not used, but vinegar or a 2 per cent to 4 per cent acetic acid solution may be used as a lavage to be followed by cotton- seed oil. If the respiration ceases, hold the tongue forward and give arti- ficial respiration by the compression of the chest or the use of the pulmotor. As a general stimulant give caffeine sodium benzoate grains five to ten intramuscularly. EMERGENCY MEASURES 373 Carbon Monoxide Poisoning- Yandell Henderson, Haggard, and their associates have worked out a standard of exposure to carbon monoxide which may be ex- pressed according to the rule, that if the product of A, the time of exposure in hours, and B, the concentration of the gas in parts per 10,000 of air, equals 3 or less, there is no appreciable physio- logical effect. If it equals 6, there is sometimes slight malaise. If it equals 9, a headache with some nausea is produced in most peo- ple. If it equals 15, anything beyond brief exposure is dangerous, and if it equals more than 15, even brief exposures are extremely dangerous. Carbon monoxide is the chief toxic agent in illuminating gas, in exhaust gas, and in smoke. The whole effect of carbon monoxide is due to its combining with hemoglobin and the resulting exclusion of oxygen. As the blood gradually takes up more and more CO, the increasing oxygen deficiency induces an increase in the minute volume of air breathed and consequently augments the absorption of the gas. At the same time, there is a washing out of carbon dioxide, thus the stimulus to the respiratory centre is lost. If ex- posure is continued, respiration stops. If the subject is rescued at this point in profound coma, and not treated, the breathing for 30 to 45 minutes is extremely feeble and very little CO is eliminated. As the carbon dioxide reaccumulates during this quiet period, the respiration gradually returns to nor- mal. The carbon dioxide balance must be restored to normal and the blood alkali reserve reestablished. The carbon monoxide combination with the hemoglobin is read- ily reversible and the affected and revived red cells are in no way impaired as a result of the poisoning. The patient recovers or dies, depending upon the injury wrought during asphyxia and the remedial forces of nature. On the basis of these physiological facts institute the following measure: In acute asphyxia, artificial respiration, preferably according to the method of Schaefer, is sometimes successful. The patient is placed in a prone position on the ground or floor with a thick folded garment or blanket underneath the chest and epigastrium. The operator then puts himself astride the pa- 374 METHODS IN MEDICINE tient or alongside, facing the head. The hands are placed on each side over the lowest ribs, and the arms are held extended. The weight of the operator's body is then slowly thrown forward, borne on the extended arms and the thorax of the subject is pressed upon and the air is forced out of the lungs. Pressure is gradually re- laxed by bringing the body up again to a more erect position with- out moving the hand. These movements are repeated regularly 12 to 15 times per minute until normal respiration begins or at least for half an hour or more. The patient should be kept -warm. The specific treatment, based on the physiologic data, consists in the immediate administration of a mixture of 8 to 10 per cent carbon dioxide in oxygen. Under the inhalation of this mixture, the breathing rapidly returns to normal, or even becomes hyperp- neic. This stimulation of the respiratory centre results in full ventilation of the lungs, washing out the carbon monoxide by mass action of the oxygen in the alveoli. The special apparatus required consists mainly in a tight fitting mask so that there will be a minimum wastage of oxygen carbon di- oxide. The apparatus for treating gassed soldiers is being improved and adapted to this purpose by the U. S. Bureau of Mines. The gas oxygen anesthesia apparatus may be used. The therapy, to be completely effective, must be applied within less than an hour to terminate the tissue asphyxia at the earliest possible moment, that is, before the harm is done. The cerebral symptoms as headaches, etc., due to cerebral oedema, can be relieved by the intravenous administration of 100 c.c. doses of 15 per cent hypertonic sodium chloride solution. Reference: Haggard, H. W., and Henderson, Yandell: Jour. Amer. Med. Assn., October, 1921, Ixxvii, 1065. The Treatment of Mercury Bichloride Poisoning Lambert and Patterson at St. Luke's Hospital, New York, worked out the following decidedly vigorous routine which proved suc- cessful in 16 out of 18 cases. EMERGENCY MEASURES 375 The first vomitus or gastric contents available must be saved and examined for mercury, as described under Methods, Part II. Copious gastric lavage with water is carried out, or copious vomit- ing of ingested water is induced as soon as a case of mercury bichlo- ride poisoning is admitted. After the stomach is completely washed and the returned fluid is clear, a mixture of 250 c.c. of milk and 100 c.c. of 50 per cent albumin water (whites of 2 to 4 eggs) is administered. The stomach wash as described is done every three hours during the first day, and twice or thrice daily thereafter un- til the urine is free of mercury. From the very start the patient is given the alkaline solution or "imperial drink" in 250 c.c. amounts, every other hour alter- nating with milk 250 c.c. on the intervening hours. The alkaline solution or imperial drink somewhat similar to the old English "potus imperials " consists of I) Potassium bitartrate 2 grams Sugar 2 " Milk sugar 2 " Lemon juice q.s. to taste Water boiled up to 250 c.c. A Murphy drip of an alkaline solution of about 1 per cent potas- sium acetate (5 grams potassium acetate in 500 c.c. of water) is given regularly as fast as the patient can absorb it. High colonic irrigations with lukewarm water are administered twice daily. The patient is subjected to a good sweat in a hot pack or by other means once each day. Lewis and Rivers at the Johns Hopkins Hospital suggest in addition to the above procedure the following: The intravenous injection of 300 to 500 c.c. of a 5 per cent to 50 per cent concentration of glucose solution to preserve the body protein. A rectal injection of a saline-bicarbonate solution (15 grams so- dium bicarbonate in 250 c.c. of normal saline) every 3 hours for 3 days. No food for 4 days, a milk diet after the fourth day, a meat 376 METHODS IN MEDICINE free diet beginning on the seventeenth day, and a full regular diet after the twenty-sixth day. Weiss and Freyhof of the Cincinnati General Hospital advocate a few modifications of the Lambert-Patterson routine. The first gastric lavage is done with a liter of milk containing the whites of three eggs. After this, water is used. After the first lavage 90 grams of magnesium sulphate in 180 c.c. of water are left in the stomach, and a soap suds enema is given. The alkaline imperial drink is modified as follows: 1/ Potassium bitartrate 4 grams Sodium citrate 2 grams Sugar 4 grams Lemon or orange juice to taste Water to 250 c.c. It is best to add the potassium bitartrate and sodium citrate to the lemonade or orangeade just before it is served. The Murphy drip method, with Fischer's solution, is carried out. Fischer's solution contains: Sodium carbonate 10 grams Sodium chloride 15 grams Distilled water 1000 c.c. Fischer's solution is also given intravenously in amounts from 1000 to 1500 and occasionally to 2000 c.c. No hard and fast rule is laid down as to the giving of this solution intravenously. The decreased amount of urine and the persistent acidity to a saturated alcoholic solution of methyl red indicate intravenous injections, to be repeated until the urine is alkaline. Occasionally when the patient has vomited immediately or within fifteen minutes after taking the poison, the urine output is not diminished and the urine becomes alkaline on oral and rectal medication within 12 to 24 hours, and intravenous therapy may be omitted. References: Lambert, S. W., and Patterson, H. S.: Arch. Int. Med., 1915, xvi, 865. Lewis D. S., and Rivers, T. M.: Johns Hopkins Hosp. Bull., 1916, xxvii, 193. "Weiss, H. B.: Jour. Am. Med. Assn., 1917, Ixxviii, 1618. EMERGENCY MEASURES 377 Treatment for Phenol Poisoning- Gastric lavage with 10 per cent ethyl alcohol, to aid in dissolving as much of the phenol as possible, should be attempted. Then la- vage with saturated solutions of magnesium or sodium sulphate, in the hope of forming insoluble sulphocarbolates, should be carried out. After the lavage 100 to 150 c.c. of the sulphate solution should be placed in the stomach through the tube and allowed to remain there to act as a brisk purgative. To combat the threatening, often inevitable, coma, collapse and respiratory failure, heat should be applied to the extremities and powerful general stimulants as caffeine, strychnine and adrenalin should be given subcutaneously. Whiskey may be used alone by mouth or in a strong coffee whiskey enema. Artificial respiration may be necessary. Treatment for Wood Alcohol Poisoning Methyl alcohol poisoning should be suspected in any case admit- ted with the complaints of vomiting, abdominal pain, and sudden blindness, diplopia or dropping eyelids. Test on p. 155. The patient should be made to vomit or, if possible, the stomach tube should be passed, provided the patient is not comatose or deeply cyanosed with depressed respiration, and vigorous gastric lavage instituted with an alkaline solution of 1 or 2 per cent sodium bicarbonate or calcium chloride (Mongel) in warm water. After the first lavage 100 to 150 c.c. of 50 per cent magnesium sulphate is run into the stomach through the tube. Lavage should be re- peated three to four times daily for three to four days. High colonic irrigations bidaily are considered of value. Lumbar puncture with drainage of the spinal meninges is usu- ally successful in allaying restlessness and clearing the mental state, and often the cyanosis also. The drainage may be repeated three to four times with benefit, especially with regard to the vision (Zethelius). Hyoscin hydrobromide together with a diapho- retic may be used if the restlessness does not respond to lumbar puncture with spinal drainage. Elimination through sweating brought about by hot drinks, hot packs, steam baths or diaphoretics as ipecac, apomorphine or pilo- carpin in small doses often produces encouraging results. 378 METHODS IN MEDICINE The blood C02 should be determined by the Van Slyke-Cullen method immediately upon admission and steps should be taken to combat the degree of acidosis that is present. To this end sodium bicarbonate in 5 per cent solution has been given intravenously with success (Harrop and Benedict), and Fischer's solution (so- dium carbonate 0.37 per cent or sodium chloride 1.4 per cent) has been given in 1000 c.c. amounts intravenously. Alkalies are also given by mouth and per rectum by the Murphy drip in doses rang- ing from .5 grams to 3. grams in a glass of water every 2 to 3 hours until the urine is alkaline to the saturated alcoholic solution of methyl red. Care, of course, must be taken not to produce an alkalosis. Harnack's conclusions that rapid oxidation of methyl alcohol yields carbon dioxide and water as products, while slow oxidation results in the formation of formaldehyde and formic acid suggest that the use of an oxidizer as oxygen, which has been used to sup- port the circulatory system and relieve the cyanosis, is of value. Bleeding has been resorted to where there is evidence of circu- latory embarrassment. Potassium iodide solution and arsenous and mercuric iodide have been used to help in the elimination of toxins. Forced fluids, and especially alkalies, are of aid in the elimination of the poison and its products. Stimulants as caffeine, camphor, strychnine, adrenalin and digi- talis have been used and are recommended. A competent ophthalmologist must be called in immediately to take care of the eye condition. Dionin (Fenton) and negative gal- vanism (Ziegler) have been recommended. References: Zethelius, M.: Hygeia, 1920, Ixxxii, 45. Harrop, G. S., and Benedict, E. M.: Jour. Am. Med. Sc., 1920, Ixxiv, 215. Fenton, R, A.: Am. Jour. Ophth., 1920, iii, 284. Zeigler, S. L.: Jour. Am. Med. Assn., 1921, Ixxvii, 1160. Acute cocaine poisoning is not an infrequent postoperative com- plication, especially in nose and throat and minor surgery. The general rule has been to treat these cases symptomatically. In the erethistic type with convulsions, as in the case of strychnine poi- soning, and especially when there is an elevation of the blood pres- sure, inhalations of amyl nitrite or chloroform in small amount are Treatment for Acute Cocaine Poisoning EMERGENCY MEASURES 379 given. Other sedatives have been advised, but all of these must be used with great caution. Mayer has shown that morphine increases the toxicity of cocain and must therefore be avoided. In his experi- mental work on frogs, calcium chloride markedly inhibited the toxic action of the drug. All sedatives, especially those that have a central action, are to be used with the greatest caution if at all because of the danger of increasing the depression which may come on in the later stages. In the torpid type this excessive depression presents itself for symptomatic treatment. Hot coffee and caffeine in other forms, strychnine, aromatic spirits of ammonia, spiritus etheris, spiritus frumenti, and adrenaline are used as stimulants. Reference: Mayer: Schweiz. Med. Wclinsehr., 1921, xxxiii, 767. Treatment for Strychnine Poisoning Slight convulsions may be controlled by amyl nitrite inhalations, while chloroform inhalations are usually necessary in any general- ized convulsion. The stomach tube should be passed immediately but only after the inhalation of either of the above drugs, for the irritation will initiate a convulsion. Old reboiled tea or tannic acid solution is used to lavage the stomach as the chemical antidote. Insoluble strychnine tannate which is formed is immediately washed out. Bromides (4 grams) and chloral (1 gram) are often given directly into the stomach through the tube. The control of the convulsions by inhalations of chloroform is, however, the safer and more easily controlled procedure. Treatment for Acute Morphine Poisoning Vigorous gastric lavage with lukewarm water. Dilute potassium permanganate or tannic acids have been used as chemical anti- dotes to oxidize the morphine but their effects on the stomach mucosa are more certain than effects on the morphine. One hundred to 200 c.c. of 50 per cent magnesium sulphate is placed in the stomach through the tube upon the completion of the lavage. Brisk purgation removes the drug from the bowel and stimulates further excretion into the bowel. Gastric lavage and purgation should be repeated in 4 to 6 hours. 380 METHODS IN MEDICINE Hot strong black coffee is given per rectum or caffeine sodium benzoate in 0.5 gram (7% grains) doses subcutaneously is given as a respiratory stimulant. Strychnine in 2 to 5 mg. doses (%0 to %0 grain) has an antag- onistic action to morphine, stimulates the respiratory center and increases the reflex excitability. Bornstein advises the use of adrenalin hydrochloride in 0.5 to 1. mg. doses as a general and especially an active respiratory stim- ulus as proved by his experiments. Atropin, at the same time, was found to have no effect and consequently he advised discon- tinuing its use. External or skin stimulation by various means of irritation is of value. Exercise and artificial respiration with the rebreathing of air to increase its CO2 content or the administration of air with C02 to the extent of 10 per cent, are means generally advised for stimulating the respiratory center. Brauer reported success in hopeless cases, following tracheotomy with the prolonged playing of a current of oxygen gas directly into the trachea. Artificial respiration must be carried out after the respiratory center fails, as long as the heart keeps on beating. References: Bornstein: Deutsch. Med. Wchnschr., 1921, xlvii, 647. Brauer: Deutsch. Med. Wchnschr., 1921, xlvii, 142-254; Therap. d. Gegenw., 1921, Heft. 1. Treatment of Acute Alcoholism The stomach should be evacuated promptly and gastric lavage thoroughly carried out. A brisk purge with 100 to 150 c.c. of 50 per cent magnesium sulphate or 2 to 3 gm. of compound jalap powder placed in the stomach through the tube after the lavage. Excessive vomiting should be treated with bits of chipped ice, spirits of chloroform and lavender, spirits of ammonia, small doses of ipecac or cocaine. Consciousness may be restored at times with small 5 c.c. doses of dilute (5-10 per cent) acetic acid or ordinary vinegar. External heat should be applied to the body and ice to the head and back of the neck when cerebral symptoms present. Caffeine, strychnine, adrenalin, and atropin and counterirritation are occasionally nec- essary stimulants. CHAPTER XXVI EMERGENCY MEASURES IN GENERAL DISEASES Treatment of Acute Heart Failure The treatment of acute heart failure with angina pectoris dif- fers considerably and distinctly from the treatment of acute heart failure with congestion and edema. During an attack of severe cardiac pain of the anginal type an inhalation of the contents of a pearl of amyl nitrite 0.3 c.c. (5m.) must be administered or nitroglycerin tablets .6 mg. (%00 gr-) should be given on the tongue, one as soon as the other is dis- solved for three doses. Spirits of nitroglycerin, drops three, may be used in a similar way. The patient must not be allowed to ex- ert himself to the slightest degree and must be kept in bed. Everything that is known to bring on the attack, such as exercise, excitement, distention after eating, smoking strong tobacco and the drinking of strong alcoholic beverages must be avoided. In heart failure with congestion and edema the patient often presents dyspnea, orthopnea, conspicuous cyanosis, engorged neck veins, an enlarged and painful liver with or without jaundice, anasarca, hydrothorax, and ascites. The heart is usually consid- erably enlarged. The indications are to relieve the venous stasis, increase the vital capacity and conserve the energy of the heart muscle by as nearly absolute rest as possible. To these ends the following pro- cedures are recommended: (1) Bleeding by venepuncture or venesection, removing 500 to 750 c.c. of blood, cuts down the load and relieves the embarrassed heart considerably. (2) Tapping or thoracentesis, removing 500 to 1000 c.c. of transu- date from the pleural sacs, both of which may be slowly drained with as little as a twenty minute interval intervening, affords relief. Ascitic fluid may likewise be drawn off by abdominal paracentesis 381 382 METHODS IN MEDICINE with benefit. The diaphragm then moves freely and the vital capac- ity is considerably increased. (3) Rest is best secured by subcutaneous injections of 15 mg. (% g'r-) morphine sulphate. The anxiety is usually relieved and sleep often follows, a "balmy sleep that knits the raveled sleeve of care." (4) Cardiac tonics are then in order. If auricular fibrillation is present, digitalization should be accomplished as rapidly as pos- sible. Intravenous injections may be resorted to; if no digitalis has been given, strophanthin .4 to .65 mg. (%5o to %oo gr-) may be given, but it is safer to use an ampule of digipuratum or digitan (100 mg. or 1% gr.). Tincture of digitalis (a good, fresh, active cat standardized, preparation) may be administered in massive doses by mouth with prompt and gratifying results, as was demonstrated by Robinson. The total amount to be given may be estimated by Pardee's standard of 2 minims of a standard tincture per pound of body weight of which never more than half, that is, an amount not exceeding one minim per pound of body weight, may be given as a single massive dose. Eggleston's standard of 0.15 cat unit, which in the case of a standard tincture of 1 cat unit per c.c. of tincture equals 0.15 c.c. per pound of body weight, gives approx- imately similar total amounts. The division of average calculated total amounts into doses, in urgent cases, is most safely accom- plished by following Eggleston's suggestions. One-third to one- half the total calculated amount in the first dose. One fifth to one- fourth of the total amount is administered six hours after the first dose, and one eighth to one-sixth the total amount twelve hours after the first dose and one-tenth the total amount every six hours after the third dose until maximum digitalization is accomplished. The criteria of adequate digitalization consist in nausea and vom- iting, a fall of the heart rate (not the pulse rate) to or below 60 per minute, the appearance of frequent extrasystoles, definite heart block, marked phasic arrhythmia or coupled rhythm. In the case of acute heart failure, with the cardiac mechanism remaining regular, the treatment is about the same as outlined except that the digitalization is not carried on so actively, but more according to the method used for nonurgent cardiac cases. (See below.) Strychnine in 3 mg. (%0 Sr-) doses, caffeine sodium benzoate in EMERGENCY MEASURES 383 .5 gram. (7% gr.) doses and camphor in oi] in .2 gram (3 gr.) doses are useful cardiac stimulants when injected subcutaneously. References: Robinson: Am. Jour. Med. Sc., 1920, clix, 121. Pardee: Jour. Am. Med. Assn., 1919, Ixxiii, 1822. Eggleston: Arch. Int. Med., 1915, xvi, 1. Eggleston: Jour. Am. Med. Assn., 1920, Ixxiv, 733. Acute Pulmonary Edema may develop suddenly and require prompt and active treatment. The patient should be placed in Fowler's position and supported in that position. Atropine sul- phate 1.3 mg. (%0 gr.) should be given subcutaneously immedi- ately and repeated as often as every 15 minutes for 5 doses totaling 6.5 mg. (%0 gr.). The use of morphine sulphate 16 mg. (% gr.) is questionable. Strophanthin has been given intravenously but is dangerous. If there is hypertension, .3 c.c. (5 M.) of amyl nitrite may be given as an inhalation or nitroglycerin tablets .05 mg. (%oo gr.) may be dissolved on the tongue for three doses. Aromatic spirits of ammonia, compound spirits of ether, and spiritus frumenti are of value as general stimulants. Adams-Stokes Attacks may be the presenting feature in an emer- gency heart case, and the case may terminate fatally if the proper steps are not taken immediately. The attacks usually, though by no means always, occur in the transition from a high grade partial heart block to complete block; the ventricle not being irritable or being badly damaged, does not initiate its own idioventricular rhythm and consequently there is a period of ventricular asystole. It is during this interval that the patient has the syncope and con- vulsive seizures, and if too greatly prolonged, death may result. Adrenalin hydrochloride %Ooo in -5 to 1 c.c. doses intravenously, if there are systoles to carry the drug to the heart, will increase the irritability of the heart muscle and probably by its action on the vagus lower the resistance and thus increase the conductivity of the His bundle and allow the auricular impulses to reach the ventricle. Atropine sulphate 1.3 mg. (%0 gr.) subcutaneously repeated for as many as five times at 15 minute intervals will likewise paralyze the vagus, and thus reestablish aurieuloventricular conduction, when the damage to the His bundle has not been excessive. 384 METHODS IN MEDICINE Thyroxin 1 mg. (%5 gr.) intravenously has a stimulating effect upon the heart muscle, increasing its irritability like adrenalin. Thyroxin is not known to have produced ventricular fibrillation as adrenalin is thought to do in rare instances in the human heart, as it does in the dog's heart. As ventricular fibrillation is not com- patible with life and adrenalin may produce it, thyroxin may be the safer of the two drugs. If the heart has stopped for thirty or forty-five seconds, and life seems to be extinct, it is heroic therapy to inject the adrenalin or thyroxin intracardiacly, through a long needle. In cases with repeated attacks of Adams-Stokes syndrome with a frequent change from incomplete to complete heart block, it is best to digitalize the patient and keep him in complete block (Lewis) for there is greater danger of the attacks reappearing, and greater danger from the attacks, than from the slowed rhythm of complete heart block. When the signs of heart failure with congestion and edema are present and also evidence of defective auriculo-ventricular con- duction or heart block of low grade and digitalization is desired for its diuretic effect and whatever effect it has on the heart mus- cle, it can be accomplished with the help of atropine. Atropine in 1.3' mg. (%0 gr.) doses per day will paralyze the vagus and coun- teract all the effect of moderate doses of digitalis on that nerve and the His bundle, and consequently prevent the undesirable effect of increasing the block, and even in itself lessen the block, and allow the digitalis to have its effect on the heart muscle, cir- culatory system, and kidney. Routine Management of Heart Cases History, physical and laboratory examinations are to be com- pleted within 24 hours after admission. Cardiac sheets are to be filled out by heart station officer within 48 hours after admission. Electrocardiograms should be taken as soon as possible after admission. Vital capacity estimations are to be made and charted on ad- mission, and daily thereafter. Blood pressure must be recorded daily and charted. EMERGENCY MEASURES 385 X-ray plate of chest taken at 7 feet, i.e., a heart plate for actual dimensions is ordered routinely for each heart case. The phenolsulphonephthalein test is done and the blood non- protein nitrogen determination if the P.S.P. is below 40 per cent in two hours. All heart cases are to be placed on the medium nephritic diet (3'5 gm. protein) (See Diets, Part III) and have a routine standard fluid intake of 1000 c.c. per 24 hours checked and charted and the complete urine output collected in routine 12 hour specimens and charted from the day of admission. Phenolsulphonephthalein tests are not to interfere with the col- lection of the routine 12 hour specimens. The quantities of urine excreted during the test are to be added numerically to the quan- tity of the 12-hour specimen. P.S.P. tests are to be done on the day of admission and repeated within a week and after effective digitalis therapy. All heart cases are to be weighed, and have the body length or height measured, on admission. Each case shall be weighed daily thereafter in the weighing truck if necessary, as per order of doc- tor in charge of ward (who is to be consulted when any question concerning this arises). In cases of auricular fibrillation the heart rate is to be counted at the apex with a stethoscope, and the radial pulse rate counted at the wrist and both charted twice daily by the interne. Morphine may be given as necessary, but cathartics, diuretics and digitalis should not be started until the heart station officer is consulted. Digitalis Administration in Massive Doses The heart rate at the apex is counted with a stethoscope and the pulse rate at wrist is counted and both are charted by the interne at least twice daily for three days before the administration of a massive dose of digitalis. Electrocardiograms are to be obtained before the drug is given. Heart plates taken at 7 feet are desirable before and after ad- ministration and are to be considered in selected case where there seems to be cardiac dilatation that might change with effective digitalis therapy. Digitalis is to be given routinely in massive doses, estimated and 386 METHODS IN MEDICINE divided according to Eggleston's suggestions, the dose to be deter- mined by consultation. After administration of the drug, which is most conveniently be- gun at 4 a.m. with 50 per cent of estimated dose, 25 per cent six hours later, and the last 25 per cent 12 hours after the initial dose, the following observations are made: The heart rate is to be counted at the apex by stethoscope and recorded with the pulse rate at wrist on an apex-radial chart % hour, 1 hour, 1% hours, 2% hours, 3 hours, 3% hours, 4, 5, 6, 8, 10, 12, 18 and 24 hours after the initial massive dose of the drug and every 2 hours for two days, then twice daily. Some digitalis effect is expected within 3 to 6 hours, while the maximal effect should be present in 18 to 36 hours. Blood pressure readings are to be recorded every two hours dur- ing the day for two days in selected cases and then twice daily. Electrocardiograms are to be taken at 3, 6, 12 and 24 hours after administration of the drug and then daily. The Diuretic Observation for all Edematous Cases Regular cardiac routine with a standard fluid intake at 1000 c.c. with the collection of routine 12 hour urine specimens is instituted, daily weight estimation and record is important, as is also the intake and output chart. 1. The patient must be strictly confined to bed and is to rest for three days. No saline cathartic, no diuretic, and no drugs ex- cept morphine are to be administered. 2. A course of theocin .1 to .3 gm., as per doctor's orders, for 3 doses at three hour intervals is to be given first. The patient is then to rest again for three days without medication. A course of diuretin (Theobromine sodium salicylate) may be then tried. 3. The Karell or Epstein diet may then be resorted to, in the hope of limiting the fluid and salt intake upsetting the water metabolism and starting diuresis. 4. The Hay concentrated salts method, consisting of an ounce of Glauber's or Epsom salts in not more than a half glass of water three times a day, may increase the fluid output and decrease the blood volume, and thus relieve the cardiac embarrassment. The strain of defecation efforts is, however, great. EMERGENCY MEASURES 387 5. Digitalization.-Eggleston's rapid method for nonurgent cases is used for regular, as well as irregular, cases. It consists in giving one-fourth of the calculated total dose at each of the first two doses, given at six hours interval; thereafter one-tenth to one- eighth of the calcidated total amount every six hours until digital- ization is accomplished. Before administering large doses of digitalis, as Eggleston sug- gests, one must be sure that the patient has had no digitalis within the preceding ten days. If he has been taking digitalis within ten days, electrocardiograms should be taken to determine whether or not there are evidences of digitalis action, such as inverted T waves and lengthened P.R. intervals. If there are no evidences of digitalis action, the procedure may be carried out as outlined, but the total amount reduced to 75 per cent of the calculated amount. If there are evidences of partial digitalization, it is safer not to give more than 50 per cent of the total calculated amount, which is divided equally between the first three doses at six-hour inter- vals. If very urgent, however, 75 per cent may be divided between the first three doses at six-hour intervals and then one-tenth the total amount given every six hours until digitalization is complete. When the cat unit of the digitalis preparation is not known, 100 mg. may be taken as the cat unit but not more than 75 per cent of the calculated total amount should be given in the first three doses. When the patient cannot be weighed or when marked edema or general anasarca is present, the net body weight must be esti- mated as closely as possible but not more than 75 per cent of the total amount calculated on this basis should be given in the first three doses. 6. Quinidin Therapy.-All auricular fibrillation cases that pre- sent no signs of heart failure, and who have had no digitalis for ten days are to be given quinidin sulphate with the hope of arresting the auricular fibrillation and reestablishing the normal mechanism. The routine as outlined for massive doses of digitalis observations should be followed in the quinidin observations. Following the method of Frey a preliminary test dose of .1 gm. (2 grains) is given to guard against idiosyncrasy to the drug. With no evidence of hypersusceptibility the drug is administered 388 METHODS IN MEDICINE in .2 gm. (3 gr.) doses, increasing to .4 gm. (7.5 gr.) three times daily. The whole period of treatment should last for six to eight days. Recent cases of auricular fibrillation, such as those appearing postoperatively, especially with exophthalmic goiter, respond most readily and most permanently. The cases of long standing, espe- cially where there are complicating mechanical factors, are not only more refractive to treatment, but are also more treacherous because of the danger of embolism following the reestablishment of auricular contractions from bits that are broken off the auricu- lar thrombi that have formed during the long period of stasis. Reference: Frey: Deutsch. Arch. f. klin. Med., 1921, cxxxvi, 70. Further General Measures Following an attack of heart failure that has responded to med- ical care, the patient must be kept in bed as long as possible, at the minimum two weeks, at the maximum six weeks. During the latter part of his convalescence he should have a general massage each day. Passive movements of the extrem- ities may be added to the exercise. "The Resistant Movements," such as those of Schott, as given by T. Lauder Brunton in his "Lectures on the Action of Medicines," may be given. In selected eases the Nauheim baths, as described under hydro- therapy, may be given. The Oertel treatment may be instituted in a modified form, graduated exercises being substituted for graduated mountain climbing. The diet should be such that the fluid intake is dis- tinctly limited, and the caloric value moderately low so that the plethora is reduced and the excess fat is removed from the body. The graduated exercises build up the heart muscle as well as the somatic muscle, and the convalescent not only gets up and about, but often gets to the point where he can easily "carry on" again. These general measures are of as great importance as the drug treatment. Any case of auricular fibrillation that has not had the normal mechanism restored by quinidin must be kept on dig- italis constantly to keep the heart rate at the apex down to 75. This can be accomplished by about 20 minims of the tincture of EMERGENCY MEASURES 389 digitalis, this being the amount that is dissipated daily according to Robinson and others. Treatment for Acute Uremia The progress of an impending uremia or an acute uremia should be closely investigated as to type, for treatment will differ accord- ingly. Foster (Jour. Am. Med. Assn., 1916, Ixvii, 927, and 1921, Ixvi, 281) groups the clinical manifestations under three primary or pure types which differ widely in pathology and pathological physiology. 1. The toxic convulsive or epileptiform type, which is sometimes though not always associated with a cerebral hyperemia with or without minute hemorrhages, is the most striking type. There is, as a rule, a selective retention of the nonprotein nitrogen with the formation of toxic substances from the abnormal renal catabolism. Headache and sudden blindness often usher this type in and coma often results; there is, however, not infrequently recovery. 2. The retention type simulating the urinary poisoning of Ascoli, the cardio-renal complex, where the heart begins to fail to shoulder its burden of supplying granular kidneys with sufficient fluid to keep up the high volume of dilute urine necessary to free the body of its nitrogen waste. There is a progressive nitrogen retention and the patient develops stupor, asthenia, anorexia, mental clouding, and often mild delirium. Edema sometimes develops with the in- creasing cardiac embarrassment. 3. The cerebral edema type is associated with the large white kidneys of parenchymatous nephritis, with salt and water reten- tion. Exceptionally these cases develop uremic symptoms, espe- cially amaurosis due to edema of the retina, vomiting, headache, stupor, and coma. Lumbar puncture shows the cerebrospinal fluid to be under increased pressure and drainage of the spinal fluid often clears the patient's mental state temporarily. In the treatment of acute uremia, it is important to remember that with starvation the body protein is broken down and thus the blood nitrogen continues to rise. Nitrogen and salt containing diets must likewise be withheld. Carbohydrates and fats alone remain. Glucose has a protein sparing property and is conse- 390 METHODS IN MEDICINE quently used with advantage. It may be given simultaneously in a 5 to 50 per cent solution in amounts from 100 to 500 c.c. It has also been given intraperitoneally with success. Bleeding, withdrawing 250 to 750 c.c. of blood by venipuncture under sterile conditions, often results in distinct improvement. The corpuscles may be washed free of serum, suspended in normal saline and reinjected. The practical results, however, do not justify the effort. Fischer's solution (see mercury bichloride poisoning) or normal saline may be used intravenously, and per rectum. Elimination must be secured through the skin and through the air baths. Purgation with saline cathartics, gastric lavage, and high colonic irrigations, are valuable therapeutic procedures. Cardiac therapy is indicated where there are any suggestions of failing myocardium. In the hypertensive type, the vasodilators as amyl nitrite, nitroglycerin and erythrol tetranitrate may pro- duce a good diuresis. Convulsions may be stopped by lumbar puncture, but occasion- ally bromides, chloral, morphine, and chloroform are necessary to control the symptoms of cerebral irritation. After the uremic attack the patient is to be treated according to the principles for the treatment of the nephritis that is present. Routine Management of Renal Cases In acute nephritis, the patient should be kept warm in bed and carefully protected from exposure, especially to cold drafts. Any cause of renal irritation should be treated and removed when pos- sible. Elimination must be secured through the skin and through the gastrointestinal canal. Sweating may be produced in an electric light bath, a hot air bath, or a hot wet pack. The patient's pulse and general condition must be carefully watched during the diapho- resis. Purgation is most satisfactorily obtained by the use of saline cathartics. Fluids as a rule should not be limited unless there is increasing edema. In the presence of a developing anasarca, the salt intake should be sharply curtailed. The low protein, salt poor diet is used routinely and seems to sat- EMERGENCY MEASURES 391 isfy the requirements. The milk diet in spite of its protein content, has been shown in its long experience to be without injury and on the contrary to be quite beneficial. In chronic nephritis, each patient must be treated individually according to the pathologic physiology that he presents. The kidneys must be spared as much work as possible. This can be accomplished in the first place by limiting the intake of nitrogen to just that amount that is easily taken care of, as can be determined by frequent blood analysis. Secondly, the increased functioning of the skin and the gastrointestinal tract may aid in the nitrogen elimination. Sweat baths and frequent saline cathar- tics are useful adjuncts to the treatment. The diet, however, should be sufficient to keep the patient in nitrogen balance without the danger of the destruction of the body protein. The fluid intake should be kept high, at least three liters per day. The heart muscle energy should be carefully conserved by avoid- ing all undue effort or exertion that would tax the reserve of the myocardium. Every effort must be made to prevent an exacerbation of acute nephritis on an old chronic lesion. The low, medium, or high protein diet is given according to the findings. In the parenchymatous type of nephritis, which Epstein (Jour. A. M. A., 64:444 (1917) and Amer. J. Med. Sc., 154:638 (1917) and 163:167 (1922), chooses to term nephrosis, he recommends a high protein diet. Epstein's contentions are not widely accepted. Reference: Epstein: Jour. Am. Med. Assn., 1917, Ixiv, 444; Am. Jour. Med. Sc., 1917, cliv, 638; ibid., 1922, p. 163-167. Treatment for Cerebral Hemorrhage Absolute rest in bed with the avoidance of every unnecessary movement and every physical and mental disturbance are the first requirements in the treatment of any cerebral episode or apoplec- tic shock. If coma is present, the head and shoulders should be somewhat elevated and the face turned aside to prevent the dropping back 392 METHODS IN MEDICINE of the tongue. Good general nursing care with careful attention to the mouth and the body is essential. Catheterization should be done to relieve any bladder discomfort or irritation. Free watery purgation from the use of croton oil in butter pellets. Elaterin or elaterium aids in the depletion and im- proves the general condition as well as reducing the blood volume. With the high blood pressure that is usually present, bleeding seems indicated and Buzzard assumes that no harm will follow the withdrawal of 250 to 500 c.c., although he believes that bleeding has saved very few lives. Restlessness must be controlled by bromides, chloral or morphine. Convalescence should be prolonged with rest in bed, low diet and active elimination. The General Management of Hypertension Cases A sharp curtailment of the total food intake with severe re- strictions on the protein intake is most frequently accompanied by relief of symptoms. In the hospital, a low pratein, salt poor diet is given. The patient must be told specifically just what he is to do when he leaves the hospital. He is to be instructed to take only a small amount once daily of any kind of meat, fish, cheese, eggs, ripe beans or ripe peas. Hypertension patients often profess to being great salt eaters, and the avoiding of salt from the diet seems to relieve the symptoms. Tea, coffee and tobacco, since the caffein and nicotin more or less constantly stimulate the vasoconstrictors, should be avoided. Al- cohol must also be avoided. Water should be ingested freely; at least eight glasses or two liters should be taken daily. Sweat baths are of service. Purgation, with calomel and salts repeated at least three times a week, tends to lower the blood pressure and improve the general condition. Bleeding has temporary beneficial effect and is to be resorted to when there is any suggestion of an approaching apoplectic seizure, pulmonary edema or heart failure. Amyl nitrite, nitroglycerin, or erythrol tetranitrate may be given to lower the blood pressure temporarily. Potassium iodide in doses of 1 gram (15 grains) three times daily seems to do some good. EMERGENCY MEASURES 393 In women with hypertension and exaggerated menopause symp- toms corpus luteum usually gives considerable relief (Riesman), and often lowers the blood pressure decidedly. All undue physical exertion must be avoided, and the mental strain of business worries must be removed. The patient's life must be readjusted so that unnecessary cardiovascular strain is reduced to a minimum. Rest should be enjoyed for half an hour after each meal and slow recreation walks should be taken through a park for an hour or so each morning and afternoon. Hydrotherapy in the form of a neutral sedative bath at night is of service. The Treatment of Diabetic Acidosis and Coma Banting's discovery of insulin has supplied the great adjunct m the treatment of diabetic acidosis as well as the management of diabetes. Cases can be brought out of coma, if the latter has not been of too long duration by insulin in sufficient dosage. No time should be lost in giving the first injection of at least 20 units S.C. or I.V. Then 20 units are given every 3 hours until the blood alkali is normal or the FeCl2 reaction in the urine becomes faint. Then every 6 to 8 hours until consciousness returns. Alkali and glucose in 25 to 50 gram amounts are given intravenously in conjunction with the above procedure or the initial I.V. injection of 40 to 60 units in advanced cases of coma. Follow the blood sugar and alkali levels. (See p. 352.) According to Joslin, prophylaxis is the important point in the treatment of acidosis. To this end, he advises the elimination of fat and protein of the diet to prevent the formation of acetone bodies. This point, however, is not unchallenged. The elimination of acetone bodies should be increased by in- creased water metabolism. Liquids should be forced at the rate of 250 c.c. intake per hour. The increase in fluid intake may be aided by administering norma] saline solution by proctoclysis, hypo- dermoclysis and intravenous injection. The salt intake should likewise be maintained at between 20 and 30 grams per day. The patient should be kept warm by warm drinks or broth, in small quantities, warm clothing, blankets, and the application of 394 METHODS IN MEDICINE external warmth. Give circulatory stimulants. Give repeated enemas. Catheterize. Joslin advises against the use of alkalies on the basis of the dan- ger of upsetting the digestion, irritating the kidney, the produc- tion of convulsions, and the introduction of infection with resulting- sepsis. Besides these contraindications Joslin has a long series of cases of diabetes mellitus with severe acidosis, threatened with coma, who were successfully treated without alkalies. If alkalies are to be administered, it is safer to give small doses and not more than 30 grams within a period of 24 hours. Sodium bicarbonate for intravenous use may be prepared by removing the alkali from a previously unopened container by a sterile spatula and weighing it in a sterile balance pan. The correct amount is dissolved in sterile normal saline solution in a sterile beaker and diluted up to the required amount to make a 4 per cent solution. This solution does not require further sterilization and should not be boiled because the irritating sodium carbonate will precipitate. CO2 gas introduced aseptically will change the carbonate back to its original form. The work of Newburgh, Marsh, and Waller tends to show that the fats in the diet do not contribute toward increasing acidosis and that the lipemia often decreases under high fat therapy. The General Management of Diabetes Mellitus Under the heading of the Dietetic Treatment of Diabetes JXIelli- tus, Chapter XXIII, are described the main routine methods. The patient's tolerance must be established by careful diet and observation. The use of insulin with carefully balanced diets as to the patient's tolerance and the necessary amounts of the ex- tract, are used in all severe, especially juvenile and threatening coma cases of diabetes mellitus. Insulin is economically justifiably used to raise a patient's food allowance from a bare maintenance level to a working level. (See p. 352.) References: Banting, F. G.: Status of Insulin. Jour. Am. Med. Assn., (April 28, 1913,) Ixxx, 1238; Trans. Assn. Am. Physicians, xxxvii, 1923. Treatment of Heat Stroke The T.P.R.'s are to be recorded every 15 minutes. 1. Cases with, a temperature below 101° are left in bed unmo- EMERGENCY MEASURES 395 lested except for the removing of all clothing and the substituting of a sheet for covering. Aromatic spirits of ammonia 5-10 c.c., well diluted in water, may be given by mouth. 2. Cases with a temperature of 101° to 103° are to be given a cool pack, that is, they are to be wrapped in a sheet soaked in water at the temperature it comes from the hydrant tap. 3. Cases with a temperature of 104° to 105.6° are placed in sheets and sponged with tap water for ten to fifteen minutes and this is followed by sponging with ice water for ten to fifteen min- utes. The patient is then allowed to remain in the wet sheets until the temperature becomes nearly normal, when, after the patient has been rubbed dry with bath towels, dry sheets are substituted. 4. Cases with a hyperpyrexia 106° and above are first sponged with tap water for ten to fifteen minutes, and then with ice water for ten to fifteen minutes, and then in a few minutes they are rubbed with ice. When the temperature has dropped 2 degrees or more the patients are allowed to remain in wet sheets for about thirty minutes. After this time the same treatment is repeated until a nearly normal temperature is reached. 5. Cases with temperature over 110° are to have the whole trunk packed in ice (Dr. Geo. Dock). All heat stroke patients must be carefully observed until well, and new indications promptly met. If convulsions are not relieved, chloroform anesthesia is admin- istered along with the hydrotherapy. In most cases fifteen to twenty minutes of deep chloroform anesthesia relieves the convul- sions, but longer time is often necessary in the cases with hyper- pyrexia. As much as two hours of deep anesthesia is often neces- sary, with intervals! of lighter anesthesia, to determine whether con- vulsions are relieved or not. If pulse is irregular and of poor quality, strychnine sulphate 2. mg. (gr. %o) is given subcutaneously and repeated in 30 minutes. If patient has a chill, use blankets and hot water bottles to pre- vent a fall of the body temperature to a subnormal level. The blood pressure should be taken, and a genera] physical ex- amination, with special reference to the heart, lungs, abdomen, 396 METHODS IN MEDICINE and neurologic status, as reflexes and eye grounds, should be made as promptly and rapidly as possible before the treatment is begun. The method and length of treatment by hydrotherapy is deter- mined by the elevation in the temperature. The patient can usually be discharged in a day or so, if tempera- ture is normal and there are no symptoms. If there is a " mud- dled" feeling in the head, the patient should be held until this clears up. In commenting on the method of treatment, Dr. Henry A. Christian, on whose service it was worked out, says, "The main thing in the heat cases is to resist the temptation to overtreat. Use no drugs, and with your hydrotherapy reduce the temperature two or three degrees, and then desist. Do not try to bring it down to normal quickly. If you find after it has come several degrees it tends to rise repeat your hydrotherapy, but do not chill your patient. " Reference: Walker, I. C.: Observation on Heat Prostration at the Peter Bent Brigham Hospital, Boston Med. and Surg. Jour., 1911, clxv, 968. The Treatment for Shock In the medical wards the symptoms of shock may be present and require treatment following severe attacks of gall bladder or renal colic or acute pancreatitis. An analogous symptom-complex, des- ignated as vasomotor paralysis, is occasionally encountered in se- vere infections, especially in influenza, pneumonia, and typhoid fever. The symptoms of shock may be associated with acute dilatation of the stomach, perforated peptic ulcer, peritonitis, and poisonings. The indications are to treat the internal congestion that results from the great vascular relaxation in the splanchnic area. The return of the venous blood to the heart and the redistribution of the blood in the peripheral vessels and the visceral vessels, all of which are of slightly reduced or normal calibre, is what is sought. The feet, legs, and pelvis should be elevated and at times an abdominal binder may be of advantage. Heat should be constantly applied externally by means of the electric light heater, electric pads, hot bricks, or sand bags, hot cloths, or hot water bottles. 397 EMERGENCY MEASURES Hot black coffee by mouth or per rectum is of value in restoring the circulatory mechanism to its normal state. Caffeine sodium benzoate .5 gm. (7% gr.), camphor in oil .2 gm. (3 gr.), strychnine sulphate 2 mg. (%0 gr-) and atropine sulphate 1.2 mg. (%0 gr.) have been given subcutaneously with benefit. The administration of warm normal saline solution by hypoder- moclysis or intravenously is especially important where there has been a reduction of the normal blood volume. The transfusion of 250 to 750 c.c. of whole blood is still more efficacious. Adrenalin hydrochloride, in a strength of 1:250,000 (2 c.c. 1:1,000 in 500 c.c. of hot normal saline solution), may be injected slowly intravenously with striking benefit. Pituitrin likewise diluted has a similar, somewhat milder, but more prolonged, action. Ergot given intramuscularly is recommended for its blood pres- sure raising properties. Digipuratum intravenously is recom- mended as a cardiac stimulant. Strophanthin for a similar action is accompanied by more danger when given intravenously. CHAPTER XXVII MANAGEMENT OF INFECTIOUS DISEASES STRICT ISOLATION MANAGEMENT OF CONTAGIOUS DISEASES Contagious diseases may develop in patients on the medical wards, or may be admitted by mistake undiagnosed by the admit- ting officer. As soon as a contagious disease is suspected, the patient should be ordered on "Strict Isolation," which consists in permitting no visitors without special permission orders from the superintendent. No individuals are to enter the sick room without gowns. In the sick room, there is to be a gown, the inside of which is uncontaminated, a pair of rubber gloves in a basin containing an antiseptic solution for the hands (lysol % per cent solution or mer- cury bichloride 1 to 2,000 solution). Everything used by the patient must be sterilized or disinfected. Dishes are to be taken from the tray as soon as the patient com- pletes his meal, placed in the sterilizer, and boiled for 20 minutes. The marked trays used in contagious cases should be washed im- mediately after each meal with a formalin solution (1 to 500) or a phenol solution (1 to 20). Contaminated linen, gowns, or clothing are to be boiled in water for 20 minutes. Excreta, such as stools and urine, should be mixed thoroughly with equal parts of milk of lime or solution of quick lime (calcium oxide) made from freshly slacked lime and water in the proportion of 4 to 1, and allowed to stand in covered basins for one hour. Specimens ordered to the laboratory must be placed in externally uncontaminated basins, covered, labeled "infectious," and sent to the laboratory. The nurse taking care of the patient must be instructed as to the routine. A gown and rubber gloves are to be worn while caring for the patient. Only articles necessary for the patient's toilet are to be left in the room. After the toilet, all linen and utensils used are to be put directly into the sterilizers with care so as not to con- 398 MANAGEMENT OF INFECTIOUS DISEASES 399 taminate things in the utensil room. After placing the contam- inated articles in the sterilizer and closing it down with the foot lever, the attendant is to return to the patient's room, put the gloved hands through the disinfecting solutions, remove the gloves, leaving them in the solution, and then remove the gown, and with great care not to contaminate the inside of the gown, hang it up in the patient's room. After leaving the patient's room, the hands and arms must be scrubbed thoroughly with green soap and a brush and running water. Wash off the hands with alcohol. After scrubbing, turn the steam into the sterilizers and boil the contents for twenty min- utes. Empty the sterilizers as soon as possible after the steriliza- tion is completed. (For further instructions, interne will consult Part I, Chapter III, Duties of Internes, Disposal of Suspected Contagious Cases.) Regulations Governing the Handling of Cases of Acute Respiratory Disease A. Definition.- Cases of acute respiratory disease are considered to be cases ad- mitted with any of the following diagnoses: acute pharyngitis, acute laryngitis, acute bronchitis, bronchopneumonia, lobar pneu- monia, and influenza (grip). B. Admission.- Cases with the above-mentioned diagnoses admitted to the wards of this hospital are to be considered as cases of communicable dis- ease and will not be admitted to the open wards at once but will be retained in an observation ward until a bacteriologic diagnosis has been rendered. During such time as they are in the observa- tion ward they will be handled with the same precaution that would be observed in cases of diphtheria. C. Bacteriologic Diagnosis.- No cases of respiratory disease will be considered as having had a complete examination until a bacteriologic diagnosis has been made. To secure this bacteriologic diagnosis the closest coopera- tion between laboratory worker and ward physician, nurses and orderlies in attendance upon such cases will be required. 400 METHODS IN MEDICINE D. Ward Rules.- No precautions that will tend to minimize the chances of infec- tion should be neglected. When the number of cases runs high, small isolation wards will be opened, and if necessary the regular medical wards will be converted into isolation wards. The general rules apply to single or multiple cases. With isolation cases in rooms or in isolated wards aside from the general medical wards with the more or less chronic disease, nurses and orderlies in attendance will exercise scrupulous care to prevent hospital or cross infections by rigid adherence to the rules and regulations of aseptic management of contagious cases. The cubicle sheet system is to be used in all wards. Paper bags will be provided and must be used for soiled napkins and gauze. Hand disinfectant solutions will be provided for use by the physi- cian, nurses and attendants in passing from one patient to another. Ward floors must not be dry swept, but must be scrubbed at inter- vals with compound solution of cresol in the water. All physicians, nurses and attendants, are required to wear gowns, caps and masks while in the ward. Bed patients are not required to wear masks, but the masks will be strictly enforced on all patients leaving the cubicle. Paper napkins are to be provided for bed patients, who will be instructed to cover the mouth and nose on coughing, sneez- ing, etc. These must be changed when soiled. An effort will be made to keep acute cases of influenza in the same section of the ward and to prevent the congregating of convalescents in toilets, bath rooms etc. The borrowing and lending of materials between the patients is to be strictly prohibited. Pneumonia developing in the influenza wards will be treated in separate sections of the wards, and medical asepsis strictly enforced in such section. Cases of streptococcus pneumonia must be treated apart from those of pneumococcus pneumonia. General Measures in Acute Infectious Diseases Acute infectious diseases require strict confinement to bed, as the first and probably most important measure. Forced fluid intake totaling at least three liters per day is an essential measure. A liquid or at times a soft diet of palatable, easily digestible, nutritious foods, is advisable. MANAGEMENT OF INFECTIOUS DISEASES 401 Catharsis at the onset and mild laxatives if necessary to keep the bowels free are used to stimulate and aid elimination. Fresh air and sunshine in the sick room are advisable. Photo- phobia may necessitate the sacrifice of the sunshine. Symptomatic treatment is administered according to the indica- tions and the patient's genera] condition. Pneumonia In no disease is good nursing more essential than in lobar pneu- monia. Besides the general measures above outlined, which must be scrupulously carried out, the patient must be carefully observed for any signs of circulatory failure, pulmonary edema, acute gas- tric dilatation, tympanites, delirium or any other complications. Any presenting complication must be promptly treated. Sputum from the bronchi must be obtained in a sterile petri dish, as soon as possible, and taken to the central laboratory to be injected into a mouse's peritoneum for subsequent typing of the infecting pneumococcus. If the pneumococci are of Type I, the antipneumococcus Type I serum should be employed intravenously in 90 to 100 c.c. doses. Drugs, especially stimulants, are to be used as soon as any sign, such as a weak or irregular or excessively rapid pulse, appears. Caffeine sodium benzoate, camphor in oil, digipuratum, atropine sulphate, whiskey and ammonia in full doses are of value. Cold suddenly applied to the abdomen for a second may produce a ben- eficial reflex. Saline by hypodermoclysis usually aids. Attempts must be made to relieve as much pain as possible by physical means, heat and cold, and pressure or fixation, as mor- phine must be used very cautiously because of the danger of pul- monary edema. Oxygen therapy is successful when continuous over a long period of time. Fresh air throughout the course of the disease is important. Typhoid Fever Nursing1 Routine.- Strict isolation routine in a well-ventilated and well-screened room must be enforced. The rectal temperature, the pulse, and the respiration rates 402 METHODS IN MEDICINE should be recorded every two hours, and observations made at 15- minute intervals thereafter. Every sudden change must be verified. Fluids should be forced to the extent of 250 c.c. every two hours, as the minimum. The urinary output should always be 2,000 to 3,000 c.c. per each 24-hour period. The high fluid intake is essen- tial in the reduction of the toxemia by elimination, so much so that it is commonly understood that the typhoid fever patient who ingests liquids freely always recovers. The exact amounts of fluids ingested must be recorded. The diet should not be forced high caloric from the time of admission, but starvation or low caloric liquids should be employed at first, with a gradual increase in caloric value, as the state of the digestive functions is established. The Coleman-Shaffer high calory dietetic management (See Part III, Chapter II) may be gradually adopted with care. The exact caloric value of the food ingested must be recorded. The bowels must be kept free by enemata. Five hundred c.c. of tap-water at 18°-24° C. (65°-70° F.) should be given each morning. If necessary, soap-suds may be substituted for the tap water every other day. If tympanites becomes troublesome and is unrelieved by a rectal tube or turpentine stupes, enemata containing turpen- tine, asafetida or milk and molasses may be employed to advantage. A light ice bag should be kept on the abdomen continuously. An ice cap should be applied to the head, for headache or per- sistent hyperpyrexia or delirium. A tepid sponge bath at 36° C. (100° F.) should be given every four hours as long as the temperature is 40.5° C. (102.5° F.) or over. The patient must be spared every exertion and must be made as comfortable as possible. The patient must be watched closely for any complications. Any verified change of temperature of 2° or more, as a rise or a fall, must be immediately reported to the physician in charge. Like- wise, any sudden rise in the pulse rate must be immediately re- ported to the physician in charge. Any untoward symptoms, as sudden sharp pain in the abdomen or the passage of blood per rectum, should be reported at once. MANAGEMENT OF INFECTIOUS DISEASES 403 The abdomen is to be measured daily and watched for tympanites; distention of the bladder from retention; disappearance of the liver dullness; spasm or tenderness. The blood pressure must be recorded each morning and evening, and whenever any signs suggesting complications are present. The development of a vasomotor paralysis should be guarded against by saline hypodermoclysis or by stimulants, as described above under circulatory disturbance. Intestinal hemorrhage requires the stopping of all food or fluid by mouth and absolute rest. Morphine sulphate should be given subcutaneously in full doses immediately and at fifteen to thirty minute intervals until the respirations are down to 10 to 12 per minute. Respirations should not be depressed below 8 per minute. If the patient has lost considerable blood or is in shock, the trans- fusion of blood or saline should be done along with the other measures outlined above for shock. Where there is any suspicion of perforation, a surgeon should be called in, as prompt operation is the only method of treatment to be considered. The mouth should receive special attention. The teeth and whole oral cavity should be cleaned with an alkaline antiseptic solution after each meal. Albolene should be applied to the tongue and nasal mucous membrane to prevent excessive drying, and cold cream to the lips to prevent their cracking. The eyes should be irrigated with 1 per cent boric acid solution three times daily. The patient's skin must be kept dry and well powdered, and the bed sheets must be kept clean and dry and smooth to prevent the development of decubitus ulcers. Should a break in the skin appear or even a red spot develop, the part must be protected from any further pressure by ring pads or pneumatic rings. A change of the patient's position by pillowing on one side for an hour, then on the back for a few hours, and then on the other side for an hour, the procedure being done in the morning and in the evening, will not only relieve the prolonged pressure on the bony prominences, but will also prevent hypostatic congestion. The constipation of convalescence is most safely relieved by mineral oil. 404 METHODS IN MEDICINE NOTES ON THE MANAGEMENT OF OTHER TYPES OF CASES Malaria Quinine should never be given until parasites have been found in the blood, and a good smear stained with Wright's and showing the organisms has been prepared and filed for future reference. Quinine, as the sulphate in capsides, is usually given by mouth, but in urgent, severe or comatose cases the soluble quinine dihy- drochloride, which is put up in sterile ampules, is given intramus- cularly into the gluteal muscles or intravenously into the median basilic vein, in not less than one and one-half gram doses for the acute attack. Quinine is best begun or given in a single massive dose, after the temperature has definitely begun to fall, or, if preferred, di- vided doses may be given at intervals during the day. One to two grams of quinine sulphate should be given each day for three to four days, or until the blood is free of parasites, as determined by the Malaria Plasmodia Concentration Method. (See Methods, Part II Chapter III.) The patient should be warned that at any time after treatment a recurrence may develop and consequently at the first symptom the blood should be examined and if it is found positive for para- sites, another course of treatment should be carried out. The prophylactic treatment should be explained to every patient that is treated for acute malaria. The prophylactic regime (Bass) consists in beginning immediately after the completion of the treat- ment of the acute attack, with a daily dose of .6 gram (10 grains) and continuing for eight weeks. Treatment of Catarrhal Jaundice by Duodenal Lavage I. Technic (Ousley).-The patient is asked to swallow the duo- denal tube preferably after a 12 hour period of starvation. He should lie on his right side with his hips elevated and drink one glass of water. As described under Methods, aspirate the contents and test with litmus, etc., to determine whether the tube has passed into the duodenum. When the tube is in the duodenum, attach it to the irrigator, place the patient on his back and allow the irri- MANAGEMENT OF INFECTIOUS DISEASES 405 gating fluid to run in by the drip method. Ten or fifteen minutes is enough time for running in as much as 1000 c.c. Irrigation 1. Sodium bicarbonate Drams 2 8 Grams Sodium sulphate Drams 2 8 Grams Sodium salicylate Drams 1 4 Grams Water Ounces 30 1,000 c.c. Irrigation Solution 2. 20% Argyrol solution Ounce % 15 c.c. Alkaline mineral waters, such as artificial Carlsbad water may be used as a drink. A nonirritating diet with fruit juices is best, and tea, coffee or cocoa should not be used. II. Technic (Lyon).-All patients whether with bronchial condi- tions or otherwise are cautioned repeatedly against swallowing of saliva and nasal exudate. The nose is sprayed with Dobell's solu- tion; the throat is irrigated with strong potassium permanganate solution, 1 gram per 250 c.c. (1 grain to an ounce). A sterile duodenal tube is passed to the stomach in the fasting state, the residuum is withdrawn, with a sterile individual syringe for each patient, and set aside for analysis and microscopy. The stomach is washed with water, followed by liquor antisepticus alkalinus (in the hyperacid cases) or hydrochloric acid solutions (in the subacid cases), and then with sterile water again until the washings are clear. Two hundred fifty c.c. of a solution of potassium permanganate (starting with 1:15,000 and increasing to 1:8,000 is used one day, and the next day a solution of silver nitrate (1:20,000 to 1:10,000) is introduced into the stomach, allowed to remain there for three to five minutes, and then withdrawn as completely as possible. The patient is given a glass of water to drink, turned on the right side and by slow swallowing, the tube is allowed to enter the duodenum. When this is reached (in from fifteen to forty-five minutes) the duodenal contents are aspirated for study. In these cases the duodenum is usually first found to be bile free. So far this method of treatment is no different from the procedure to be 406 METHODS IN MEDICINE followed for the diagnosis of diseases of the gall bladder and biliary ducts. After the duodenal contents have been aspirated for study intro- duce through the tube 50 to 100 c.c. of 33 per cent saturated solu- tion of magnesium sulphate and bathe or douche the duodenal mucosa. By connecting the duodenal tube with a vacuum bottle (under low pressure), some magnesium sulphate remaining in the duodenum is first aspirated, and shortly this clear solution will be seen to be tinged yellow with bile. Later nothing but pure bile is obtained. The first bile obtained probably comes from the com- mon bile duct, since it is the first available supply. As the gall bladder contracts and expresses its contents through the cystic duct, it washes out ahead of it the common duct bile and presently only bile from the gall bladder seems to be presenting. After the gall bladder contents have all been expelled, continued aspiration often yields a bile supposedly freshly secreted from the liver cells into the hepatic ducts, and thence to the common duct and finally (via the duodenum) out into the vacuum bottle. In the treatment of catarrhal jaundice cases, it was found in all instances that the common duct or "A" bile was thicker and more viscid than normal, "off color," that is, deeper molasses yellow in some cases, mustard color in others, turbid and con- taining much mucus in ropy, tenacious masses and much flocculent debris. Microscopically, there were seen the products of catarrhal inflammations, in one case only, microorganisms (streptococci) were observed and later culturally proved (Lyon). The gall blad- der or "B" bile, was also found definitely "static" and "off color," thicker and more viscid than normal, and several specimens contained heavy deposits of bile crystals and some microscopic catarrhal elements. No bacteria were found in the "B" bile speci- mens. In only two or seven cases was it found to "unplug the ampulla of Vater" at the first treatment, but in all cases this was accomplished by the third treatment or before (Lyon). Treatment should be given every day until the bile duct has been freed and thereafter every second to fourth day, as indicated in these individual cases. Following the biliary drainage, the duodenum should be disin- fected with potassium permanganate or silver nitrate solutions of the same strength as used in the stomach, and the active local treat- MANAGEMENT OF INFECTIOUS DISEASES 407 ment continued as long as the microscopic evidence of duodenitis exists. Introduce only 100 to 200 c.c. of these solutions into the duodenum at one time, let it remain there from three to five min- utes and try then to recover what can be recovered (often as much as 50 per cent of the amount introduced), for no bad effects have been noted from the absorption of KMN04 or AgNO3 in the strengths up to 1:10,000, applied to the duodenum. In some in- stances the treatment may be completed by giving a duodenal enema after the method of Jutte. References: Owsley, James W.: South. Med. Jour., Oct. 19, 1919, p. 597. Lyon, B. B'. Vineent: (A) Jour. Am. Med. Assn., Sept., 1919, Ixxiii, 981. (B) Am. Jour. Med. Sc., Apr. 1920, clix, No. 4, p. 503. The Treat- ment of Catarrhal Jaundice by a Rational, Direct and Effective Method. (C) Med. Clinics of North America, March, 1920, iii, 1253. Some As- pects of the Diagnosis and Treatment of Cholecystitis and Cholelithiasis. Gastrointestinal Diseases Peptic Ulcer.-Medical treatment is indicated at some time or other in practically all cases of gastric or duodenal ulcer, either as a preoperative or preparatory measure, or a postoperative adjunct when the surgical treatment has not accomplished the expected relief, or where there is a recurrence of ulcer symptoms or in acute or chronic cases in which the treatment is or has been purely medical. The principles of ulcer therapy are based upon rest and free- dom from irritation, not only of the stomach and especially the denuded area, but also of the whole body. In other words, com- plete somatic rest as well as visceral rest. The patient must be kept warm in bed as long as a- month, but allowed up for daily bath and bowel movement. All infected foci in the mouth, nose and throat should be treated and eliminated. The teeth should be put into perfect condition and regularly cared for. If the tongue becomes furred, it should be scraped with a wooden spatula. A bland, mechanically and chemically nonirritating, minimum acid producing diet, administered in small amounts at frequent intervals gives the stomach rest. The maximum rest is secured by starvation, which is especially beneficial when the stomach is very irritable. Small amounts of foods containing a minimum of (See Diets, p. 300) 408 METHODS IN MEDICINE protein and salt tend to reduce the secretion of acid, and alkalies given at regular intervals neutralize the acid secreted and thus the main source of irritation is controlled. The heavy oxide of, or calcined, magnesia is the alkali of choice. It has four times the neutralizing power of sodium bicarbonate, does not give off CO2 gas and distend the stomach, has a mild laxative action and produces a very much smaller secondary in- crease in gastric secretion after the initial neutralization. Silver nitrate pills have been advised to suppress gastric secretion and atropine sulphate or extract of belladonna has been used for the same purpose. The latter seems the preferable one of the two, but is especially indicated only when there is spasmodic obstruction of the pylorus. Olive oil' in 10 to 15 c.c. doses is given three times a day, before food, for the same purpose. Bismuth preparations, especially the subcarbonate, are given before meals to coat the ulcer base and thus protect it. For specific directions as to treatment, see diets (Part III, Chap- ter XX). Hemorrhage or perforation in a peptic ulcer case should be man- aged just as described for a complicating intestinal hemorrhage or perforation in typhoid fever (see above). Pyloric obstruction complicating a peptic ulcer requires surgical treatment eventually. However, the patient must often be treated medically to get him into condition for surgical intervention. When the spasmodic element of the obstruction, which is always present to some degree, is playing a considerable part in the obstruction great results can be obtained by medical treatment. Nightly lavage to remove all food residue and prevent the formation of irritating products of fermentation and the administration of a bland diet with alkalies and atropine often entirely relieve the stasis. Constipation.-Acute intestinal obstruction, from an incarcerated hernia intussusception or a ring carcinoma, must be differentiated from an obstructive constipation from adhesions, stricture or ptosis. In the former prompt surgical intervention is indicated, while in the latter, medical measures, as liquid petrolatum, oil enemata, abdominal massage and exercise are more successful than surgery. The treatment further depends upon whether the constipation is of the more rare atonic type or the more common spastic type. The atonic type should receive a bulky coarse irritating diet, while ISOLATION MANAGEMENT OF CONTAGIOUS DISEASES 409 the spastic should have a soothing lubricating diet. The type of diet for each of these is outlined under Diets, Part III, Chapter XX. In general a good intake of fluid is essential. Cathartics should be used as infrequently as possible. Regularity of habits, espe- cially as to defecation and abdominal exercise, are very important parts of the regime. The fluid extract of Cascara sagrada in doses beginning with 20 to 25 minims t.i.d. and gradually decreasing the dosage is the preferable drug. It is thus to be used as a tonic laxative, and never as a purgative. Castor oil, because of its constipating after effect, does not seem desirable. Calomel followed by a saline cathartic or a saline alone is often of value to begin a treatment with, but saline should not be used routinely in the treatment of constipation. Enemata should be resorted to rather than purgatives when in the course of treatment the bowels become sluggish. Diarrhea.-In the management of diarrhea, the first thing to be done is to make a diligent search for the cause. When the cause is found and treated or eliminated, the enteritis will usually subside. The stools must be carefully studied. Rest in bed and warmth are essential parts of the treatment. Purgation to remove any suspected irritant in the intestinal canal is rational therapy. Castor oil is valuable in this type of condition, because of its secondary constipating effect. A course of calomel followed by salts is sometimes preferred. Starvation is desirable at first, until the exact status of the gastro- intestinal canal is established. Then a liquid diet with an abundant fluid intake should be instituted. The diet may be gradually increased with non-residue-forming food substances. (See Non-Residue Diet, Part III, Chapter XX.) Intestinal Parasites Treatment of Taeniasis.-The bowel should be prepared for a pe- riod of from two to five days by having the patient on a soft diet and allowing liquids only for at least two days preceding the day of active treatment. The fluid intake must total at least 4000 c.c. in 24 hours. A cathartic should be administered each evening for at least two evenings. Castor oil 30 to 60 c.c. may be given the first night, 410 METHODS IN MEDICINE while a saline purge is preferable on the evening preceding the drug as the oleoresin of aspidium is soluble in oil and once dis- solved it may be absorbed and give toxic symptoms. Calomel in divided doses is given the night before the treat- ment followed by a brisk saline purge at 6:00 a.m. in the morning of the day of active treatment. No food or fluid, other than the saline cathartic, is allowed by mouth. A prescription containing the active agents is made up as follows: R Oleoresin aspidium dr. II 8 c.c. Chloroform dr. I 4 c.c. Croton oil M II 124 c.mm. At 8:00 a.m. give one-half of the prescription. At 9:00 a.m. give the other half of the prescription. At 10 :00 a.m. give 60 c.c. of 50 per cent magnesium sulphate solu- tion. Receive all stools in a vessel containing warm water and examine all the collected specimen for the relatively minute head and neck of the parasite. Treatment of Amebiasis.-The dysenteric amebae are best at- tacked by a combination of oral and subcutaneous administration of ipecac preparations. The drug in the gastrointestinal canal is effec- tive against the amebae in the ulcers and sloughing, scar tissue enveloped pockets in the wall of the colon, while the active prin- ciple circulating in the blood will insure medication to any begin- ning metastatic foci outside the alimentary canal as, for instance, in the liver. The method of administering nauseating and emetic drugs through the duodenal tube was worked out by Freund in connection with the treatment of amebic dysentery. Powdered ipecac in doses as large as 8 grams (120 grains) may be administered through the tube directly into the duodenum and intestines. Ipecac may be given in 1.4 gm. (20 grain) salol coated tablets before each meal, but this is a slower and a less reliable method. Emetin hydrochloride is given subcutaneously in 30 mg. (% grain) doses three times a day until about 1 gram (15 grains) have been injected. Dobell, Dale and Low, and other English workers report that emetine bismuth iodide is the most efficacious preparation. A 411 ISOLATION MANAGEMENT OF CONTAGIOUS DISEASES course of 2.5 grams (40 grains) in 65 mg. (1 grain) doses taken on a full stomach three times a day, or .2 g. (3 grains) once daily for twelve days seems advisable. The powder or gelatin capsules con- taining the powder are preferable to salol-, stearate-, or keratin- coated tablets, which are often passed in the feces unchanged. The use of emetine bismuth iodide is said to make subcutaneous injec- tions of the emetine hydrochloride unnecessary. Treatment of Ankylostomiasis or Uncinariasis.-Chenopodium oil is advocated in the place of thymol in hookworm disease because it requires less careful preparation of the patient, is less nauseat- ing, and according to some observers, more efficacious. The preliminary starvation and purgation periods are unneces- sary but the drug should not be given coincidently with food according to Darling, Hartmann, and Hacker (Jour. Am. Med. Assn., 1921, Ixxvi, 419). The maximum adult dose of chenopodium oil is 3 c.c. but the usual dose is 1.5 c.c. For children the dose must be reduced. The dose is divided into two equal parts of 1.5 c.c. each for adults, placed in freshly prepared hard gelatin capsules, and given two hours apart. The last capsule is followed in two hours by a saline purge. The treatment is often repeated in three days. Enemata Cold Water Enema Tap water, 18° to 22° C. (65° to 70°), 1 to 2 quarts (500-1000 c.c.). Give quickly and have patient expel it as soon as possible. Use short tips. Inject rapidly, but try to avoid spasm and colic. £. >8. Enema Soap Suds 1 pint to 1 quart (250-500 c.c.). Liquid soap is rubbed up with warm water to make a good lather. S. and G. Enema Soap Suds quarts 1 to 2 (500-1000 c.c.). Glycerine oz. % (av. oz. 2) (60 c.c.). Peppermint Enema Peppermint oil dram 1 4 c.c. Soap Suds (warm) quart 1 500 c.c. 412 METHODS IN MEDICINE M. G. and W. Enemata Mag. Sulph. Crystals oz. 2 60 G. Glycerine oz. 2 60 c.c. Water oz. 2 60 c.c. Oil Enema, Formula 1 Warm cottonseed oil oz. vi 180 c.c. Give high and follow in 2 hours with a soap suds enema (per physician's orders). Oil Enema, Formula 2 Cottonseed oil oz. 4 120 c.c. Turpentine oz. % 15 Castor oil oz. 2 60 c.c. Mag. Sulphate oz. 1 30 c.c. Give high and follow in 2 hours with soap suds enema (per physician's orders). W. and G. Enema Water oz. 3 90 c.c. Glycerine oz. 3 90 c.c. O. and G. Enema Cottonseed oil oz. 3 90 c.c. Glycerine oz. 3 90 c.c. Asafetida Enema Tincture Asafetida dr. 2 to oz. 2. 8 to 60 c.c. (Per physician orders.) Water oz. 8, 240 c.c. Follow in one-half hour with S.S. enema. Turpentine Enemata Formula 1: Turpentine oz. % 15 c.c. (Per physician's orders Warm oil oz. 8 240 c.c. Follow in y2 hour with S.S. enema. ISOLATION MANAGEMENT OF CONTAGIOUS DISEASES 413 Formula 2: Turpentine dr. % to 4 2 to 16 c.c. (Per physician's orders.) Soap suds pints 2 1000 c.c. See that turpentine is thoroughly mixed with the soap solution. Formula 3: Turpentine oz. % 15 c.c. Castor oil oz. % 15 c.c. Mag. Sulphate oz. % 15 c.c. Egg one (may be omitted). Milk and Molasses Milk and Molasses, equal parts, average oz. 6 or 180 c.c. of each. Enema Notes For all cleansing enemata, when large amounts of fluids are to be given, use can and enema tip. For all enemata and where small amounts of fluid are to be given, use a funnel and rectal tube. In giving medicine, per rectum, do not give it in more than 150 c.c. of fluid. Except in case of "cold water" enema, have solutions warm. Rectal Tubes Insert for a distance of eight inches. Unless otherwise ordered, rectal tubes are not to be left inserted for longer than one-half hour. Rectal Taps Tap Water at 65° F. (18.5° C.) is given as a simple enema in large amounts, 500 to 1,000 c.c., but in smaller amounts, 250 c.c. to 500 c.c., it is given to be retained and absorbed. Normal Saline at 65° F. (18.5° C.) may be given in the same way. Sodium Bicarbonate 4% likewise. Glucose Solution 4% likewise. 414 METHODS IN MEDICINE Alkali Sugar solution often given per rectum by the flush or drip method in acidosis cases. 4% Sodium bicarbonate. 4% glucose. .065 gm. Sod. Acetate per 500 c.c. Salt Solution per Rectum Apparatus. Infusion can. Rubber Catheter, size 10-14. Tubing indicator or drip bulb. Hoffman clamps. Rubber tubing for connection. Give a cleansing weak S.S. enema. Place 1 pint warm saline in the infusion can. Adjust so the top of saline will be at same level as bed. (Murphy Method) Solutions STRENGTH NO. OF C.C. OF WATER AD DESIRED 1-500 SOLUTION 1000 C.C. 1- 1,000 500 < < 1- 2,000 250 c c 1- 3,000 166-% c c 1- 4,000 125 c c 1- 5,000 100 < c 1- 6,000 83-% c c 1- 8,000 62-% < c 1- 10,000 50 c c 1- 15,000 33-% < c 1- 20,000 25 < c 1- 25,000 20 c < 1- 30,000 16-% c t 1- 40,000 12-% c c 1- 50,000 10 c c 1- 60,000 8-% < c 1- 80,000 6-% ( c 1-100,000 5 < c 1-150,000 3-% c c 1-200,000 2-% c c 415 ISOLATION MANAGEMENT OF CONTAGIOUS DISEASES Put a bottle of hot water in the infusion can. Coil the tubing on a hot water bottle in bed at the side of patient. Notice if the saline drops from nozzle when it is held at the same height as when inserted. Insert catheter about 3 inches in rectum. Keep the saline in the can on level with bed by adding a small amount of saline frequently or by putting magazines under the can, one about every half hour. The saline should drop slowly but constantly, when it is properly adjusted and is being absorbed. The patient gets about one pint (250 c.c.) every three hours. NOTES ON THE TREATMENT OF BLOOD DISEASES Anemia Secondary Type.-When possible, the transfusion of matched whole blood is preferable to any other therapeutic procedure. The direct or small syringe method of Lindeman, Duke, and others is less frequently accompanied by reaction than the citrate method. As suggested by Williams, Mellon and others (Jour. Am. Med. Assn., 1922, Ixxviii, 1024 and 1026), the causes of reactions to intravenous infusions may be that the solutions are of an improper hydrogen-ion concentration (pH). The regulation of the pH and the practical application of buffers are suggested remedies. The routine course of iron is of value. Fresh Blaud's pills are administered beginning with .3 gm. (5 gr.) doses three times daily and increased .3 gm. (5 gr.) every three days until 1.6 gm. (25 gr.) doses are reached and then the doses are decreased by .3' gm. (5 gr.) every three days. Primary Type.-Palliative measures alone are available for the treatment of this condition. Remissions sometimes appear spon- taneously, but usually they follow some type of therapy. Blood transfusions initiate remissions in about 50 per cent of cases. Ar- senic as arsphenamine or neoarsphenamine has been successful in some cases and apparently disastrous in others. Splenectomy, seem- ingly successful in some cases, especially those with enlarged spleens, should be seriously considered. In the way of symptomatic treatment, hydrochloric acid is given in divided doses after meals. With this aid, high caloric diets are tolerated with beneficial results. Food rich in iron should be care- fully given (C. P. Howard). Rest in bed is an aid in the general 416 METHODS IN MEDICINE management of these cases. Arsenic as Fowler's solution may be of benefit. The treatment and eradication of all foci of infection and the search for and treatment of any infection, such as syphilis or any intestinal parasite, as the broad tapeworm, are important measures. Leukemia A combination of methods is necessary in this condition, where the treatment is again for the most part palliative and symptom- atic. Spontaneous remissions may occur. Benzol (medicinal) in doses beginning with 5 minims three times daily may be gradually increased according to the patient's tol- erance, which may sometimes be as high as 100 minims (6.5 c.c.) three times daily. At the same time, radiotherapy, x-ray or radium exposures over the spleen, glands and long bones should be done according to the advice of a radiotherapist. The treatment should be closely followed with leucocyte counts and differential counts. The progress of the disease under treatment is thus controlled. When the leucocyte counts drop to 12,000, the radiotherapy should be discontinued and the benzol reduced to a minimum dosage of 5 minims t.i.d. or entirely discontinued. The blood study must be continued and at the indication of the activity of the disease, the therapy should be started again. Transfusion is of aid in relieving the myelophthisic or lympho- phthisic anemia and in some cases good, but temporary remissions have followed whole blood transfusion. CHAPTER XXVIII HYDROTHERAPY Action and Indications of Various Methods Employed in the Hydrotherapeutic Department Dr. Frank Ewerhardt, Director Electric Light Bath A cabinet with 48 to 60 watts tungsten (Mazda) lamps is used instead of the old fashion Turkish bath, because it is more effi- cient, more sanitary, and safer. The patient and the treatment are always entirely under the control of the operator. Action.-The bath is either tonic, derivative, or eliminative, de- pending upon the temperature and the duration. Short exposure to intense heat is stimulating, while prolonged mild heat acts as a sedative. For diaphoresis, radiant heat with maximum illumina- tion with a minimum degree of heat production is desirable, there- fore tungsten lamps should be used instead of carbon lamps. The light rays penetrate the tissues for some distance. Indications.--1. Tonic. For patients convalescing from debili- tating diseases or postoperative cases and in any case in which it seems desirable to build up the general vital resistance. 2. Derivative: To maintain a normal balance of the blood sup- ply between skin and muscles on the one side, and the abdominal organs and pelvic organs on the other. It is the treatment par ex- cellence for hypertension cases, and is also of value in venous stasis, heart disorders especially with obesity, infectious arthritis, neuritis and neurotic cases. 3. Eliminative: Wherever profuse sweating is indicated, as in uremia, chronic nephritis and gout cases, a cabinet bath is of service. The treatment is often used as preparatory to a Scotch Douche. Local Baking Electric lighted devices containing lamps of from 250 to 1500 watts for local application of radiant light and heat are used. The 417 418 METHODS IN MEDICINE light rays penetrate the tissues to some extent and are there in- stantly converted into heat. This method is more effective than the older method of conductive heat which affected the tissues layer by layer. Action.-There is produced a hyperemia for the relief of deep- seated congestion. There is a relief of the local congestion by the hastening of the return circulation. The pain is relieved and an increase of leuco- cytes for combating local infections is produced. Indications.-Local hyperemia is used for local infections, in- flamed joints, myositis, fractures, sprains, neuritis, and often as a preliminary to massage. Scotch Douche In this method of treatment streams of alternately hot and cold water are thrown from a rubber hose upon the patient at a dis- tance of twelve feet, under a pressure of 25 to 35 pounds. Action.-The effects depend upon the degree of variation of tem- peratures, the extremes being 49° C. to 4.5° C. (120° F. to 40° F.). The pounding action of water under considerable pressure acts as a massage and enhances the reaction which is the aim of the treat- ment. Indication.-A Scotch Douche is always indicated following elim- inative treatment to neutralize the depressing effect. The treat- ment is useful wherever an increased tone of muscular, circulatory or nervous systems is indicated. It is often of great benefit in sciatica, lumbago, and myositis, arthritis and in convalescent ane- mia cases. Whirlpool Bath Water at a temperature of 40° to 45° C. (105° to 120° F.) is mechanically set into violent motion and the patient or the affected part is immersed. Action.-The effect is that of a stimulant to the blood and lym- phatic circulations. It accelerates the retrogression of inflamma- tory processes and has a sedative effect in relieving pain and muscular spasm. Indications.-In army practice the whirlpool was introduced for cases of gunshot wounds which had resulted in joint injuries, stiff HYDROTHERAPY 419 and swollen joints, painful stumps, scar tissue, bone injuries, anky- losed and edematous limbs. The whirlpool bath is used in civilian practice with success in cases similar to those in which it was ap- plied in the army. Nauheim Baths The original Nauheim baths of Bad Nauheim, Germany, are nat- urally impregnated with carbonic acid, sodium and calcium chlo- rides and other salts of lesser importance. These baths have for many years been artificially prepared in this country by charging artificially prepared brines with carbonic acid, either chemically or by means of mechanical devices. Action.-Through stimulation of the vasodilators of the periph- eral or cutaneous circulation, blood is drawn from the congested visceral circulation and the heart is thereby relieved. With a re- lief of the venous stasis the left ventricle is able to produce a more complete contraction and the pulse rate is reduced and becomes stronger and fuller. Indications.-Chronic cardiac, nephritic, hypertension and neu- rasthenic cases usually improve under the Nauheim regime. Other hydro-therapeutic measures that are available: Continuous neutral sedative baths. Hot and cold sitz baths. Needle and shower baths. Salt glow baths. Hot and cold wet packs. Massage and Exercise The light stroking effleurage is useful locally, in relieving re- flexly, pain and spasm, especially in fractures and joint disorders. Generally, this type of massage has a soothing, relaxing and seda- tive effect on the body as a whole. Deep stroking or drainage is employed for the purpose of reducing swelling and congestion in the extremities. Deep vigorous massaging is used locally for the purpose of building up the muscle cells, especially in paralysis and other forms of muscle disease. General exercise is given for body building or obesity. Correc- tive exercises are used for postural defects. Reeducational gym- 420 METHODS IN MEDICINE nasties are of advantage in reestablishing coordinated movements, especially in paralysis and locomotor ataxia. Passive and late re- sistive movements are essential in convalescent heart cases, espe- cially after the establishment of compensation following an attack of heart failure. Actinic Radiation The ultraviolet rays (also chemical or actinic rays) are present in large quantities in sunlight at high altitudes where the air is free from the large quantities of solids found at a lower level, especially in the city. These rays are strongly bactericidal and exert a stimulating influence on the body metabolism. Actino- therapy has been used for some time in Switzerland, and has been adopted in the United States in the treatment of tuberculosis, skin disorders and general adjustment of metabolism. It has been found that mercury vapor when heated to a high temperature by an electric current produces a light very rich in ultraviolet rays. This source of therapeutic light has been developed commercially in the form of so-called quartz mercury lamps. Clinical and lab- oratory research has established the belief in medical quarters that this mode of therapy is a valuable adjunct in the treatment of bone tuberculosis, especially bone and skin lesions, septic wounds, mal- nutrition, rickets, and anemia. CHAPTER XXIX DOCK'S TWENTY DRUGS With the firm conviction that proficiency in the use of a few good drugs was infinitely more valuable to the student and prac- titioner than a smattering of every item indexed in the old Mate- ria Medica, the Physician-in-Chief began in 1899, at the University of Michigan, to encourage thorough study of, and practical familiar- ity with, a small list of drugs or classes of drugs. There was no in- tention of limiting practice to twenty drugs, but they were ad- vanced as a necessary basis for further experiments in therapeutics. Lectures on the twenty drugs have been given almost every year. General Rules Whenever possible each drug should be given alone so that its effects can be more clearly observed. Close observation must be made for the desired action. It is better to begin with one or at the most two preparations of a drug. In general drugs are not to be used to reduce temperature. The twenty drugs are as follows: 1. Opium. 2. Arsenic. 3. Io- dides and iodine. 4. Iron. 5. Quinine. 6. Digitalis. 7. Strychnia. 8. Salicylates. 9. Atropin. 10. Bromides. 11. Chloral, veronal or trional. 12. Ammonium chloride, balsams. 13. Phenacetin. 14. Calomel, sodium sulphate, castor oil, cascara. 15. Bismuth. 16. Nitrites. 17. Acid hydrochloric; alkali, sodium bicarbonate. 18. Ipecac. 19. Male fern, santonin, thymol or chenopodium. 20. Sera, vaccines, opotherapy, thyroxin, etc. Huchard and Fiessinger published a small book on the same subject of twenty drugs, "La Therapeutique en Vingt Medica- ments," Paris, 1910, some years after lectures on "Twenty Drugs" were begun at Ann Arbor. The list of the French authors was as follows: 1. Sodium salicylate. 2. Quinine. 3. Mercury. 4. Iodide. 5. Digitalis. 6. Iron. 7. Sera. 8. Collargol. 9. Opotherapy. 10. Bis- 421 422 METHODS IN MEDICINE muth. 11. Theobromine. 12. Sodium bicarbonate. 13. Arsenic. 14. Opium. 15. Belladonna. 16. Bromides. 17. Castor Oil, sodium sulphate or aloes. 18. Nitrites. 19. Ergot. 20. Antipyrin. THE DRUGS Opium Morphinae sulphas.-U.S.P. Dose 15 to 30 mg. (% to y2 gr-)- The drug is usually given subcutaneously in full doses for emergency conditions as hemorrhage, etc. The drug allays anxiety, relieves pain, and affords rest, which is very important in heart disease. The production of constipation by the diminished peristalsis is more often an undesired than a desired effect. The respiratory rate must be watched when repeated doses of morphine are given, so that the respirations are not depressed below ten per minute. Should the respiratory rate fall below eight per minute, stimulants such as strychnine and caffeine should be administered. Arsenic Liquor Potassii Arsenitis-U.S.P. (Fowler's solution). Dose 0.2 c.c. or 3 minims, gradually increasing by one minim per day with tolerance to 1 c.c. (15 min.). Stop if puffiness of eyes appears. Fowler's solution is used chiefly in cases in which a stimulating action on the blood-forming organs, especially the red bone mar- row, is desired. In blood diseases, especially pernicious anemia, often in leucemia and Hodgkin's disease, temporary improvement follows the administration of arsenic in full doses to tolerance. Beneficial effects follow the use of arsenic in certain neurologic and dermatologic conditions. Arsphenamine, N.N.R. Dose initial .2 gm. to .3 gm., average .3 gm. to .4 gm., rarely .4 gm. to .5 gm., intravenously. Females should always receive .1 gm. less than males under the same cir- cumstances. Arsphenamine is the most powerful spirocheticide and is con- sequently efficacious in the treatment of any type of syphilis. It is also effective in spirochetal bronchitis, relapsing fever, and the tropical infections as yaws, filaria, etc. Vincent's Angina, due to the spirochete and fusiform bacillus infection often responds to the local applications of 10 per cent arsphenamine in glycerin. dock's twenty drugs 423 Contraindications.-Arsphenamine must be given with extreme caution and only after a thorough course of mixed mercury and iodides in syphilitic involvement of the heart and circulatory sys- tem, the central nervous system, the larynx or trachea, and the eye. The danger lies in the possible Herxheimer reaction which might produce sudden death, or severe complication with irrepa- rable damage to an organ. Nephritis unless it can be proved to be of a syphilitic nature, is a contraindication to arsphenamine because of the danger of ure- mia. The ingestion of considerable alcohol and fatty foods and the use of large doses of arsphenamine predispose to acute yellow atrophy and should consequently be avoided. Iodides Potassii lodidum U.S.P. Dose .9 gm. to 4 gm. (15 to 60 gr.). It is best administered in a saturated aqueous solution which contains .065 gm. (1 gr.) to the drop. Milk is the most satisfac- tory vehicle (Dock. Geo.: Jour. Am. Med. Assn., 1909, liii, 1607). Iodide of potash has been used to an enormous extent for many years. Iodides are of value in the treatment of the late manifestations of syphilis, gummata, and aneurisms. Hypertension and arterio- sclerosis eases are symptomatically often greatly benefited by potas- sium iodide. It is an efficient expectorant and is of benefit in any type of bronchitis. In goiter regions it is a successful prophylac- tic measure, and is also effective in reducing the simple colloid types of goiter. The elimination of lead as a soluble lead iodide compound following the use of potassium iodide in lead poisoning is an established therapeutic fact. The contraindications to the use of iodides are few. Hyperthy- roidism, acute nephritis, and acute pulmonary edema may be ag- gravated. It is considered unwise by some to use the iodides in attempts to get tubercle bacilli in the sputum in suspected cases, on the grounds that the progress of the pulmonary destruction is hastened; this, however, is not a proved fact as yet. Iron Pilulae Ferri carbonatis, U.S.P. Dose .3 gm. to 1 gm. (5-15 gr.). A freshly made preparation is always essential for, even with 424 METHODS IN MEDICINE this precaution taken, a large part of the iron ingested passes through the intestinal canal unabsorbed. Iron is used in the treatment of anemias, secondary to hemor- rhage and infection, and in chlorosis, while it is generally con- sidered useless in pernicious anemia. Some consider the value of all iron therapy still unproved. Syrupus Ferri lodidi U.S.P. in 1 c.c. to 10 c.c. doses is used widely in the treatment of anemia in children. Quinine Quininae Sulphas U.S.P. Dose .3 gm. to .6 gm. (5 gr. to 10 gr.) in capsules. Quinine as a protoplasmic poison, is best known because of its specific action against malarial parasites. For the advisable method of administration see Treatment of Malaria (page 404). Quininae dihydrochloridum N.N.R. Dose 0.5 gm. in ampules is the preparation of most service for intramuscular and intra- venous therapy in pernicious malaria, especially when accompan- ied by coma. Quinidine Sulphate N.N.R. Dose .2 gm. to .4 gm. (3 gr. to 6 gr.). Quinidine, the dextrarotary isomer of quinine, while less effec- tive in malaria, has been shown by Frey to be most active in the arrest of auricular fibrillation, which action of quinine was first noted by Wenckebach. The results in the establishment of a nor- mal regular mechanism in absolutely irregular hearts have been quite spectacular. The drug should not be used when there arc signs of heart failure. (See Treatment of Heart Failure, page 387.) Idiosyncrasies to the quinine derivatives should be thought of and ruled out before large doses are given. Digitalis Tinctura Digitalis U.S.P. Dose 1 c.c. to 15 c.c. (M. 10 to dr. 4). Digitalis is the drug used universally for heart disease, as a car- diac tonic and diuretic. It has its most dramatic effect in auricular fibrillation with heart failure. (See Treatment of Heart Failure pp. 381 to 387.) Besides the preparation for oral administration, one preparation for intravenous or intramuscular therapy should be at hand. dock's twenty drugs 425 Digipuratum (Knoll) or Digitan (Merck) Dose 1. ampule 1 c.c. (U/2 gr. or 25 m. of standard tincture) a solution of physiologically standardized digitannoids is a reliable, uniform and rapidly acting preparation. Strophanthin and ouabain preparations do not remain uniform as a rule, are dangerous and consequently not advised. Strychnia Tinctura Nucis Vomicae U.S.P. Dose 0.5 c.c. to as high as 3 c.c. (8 m. to 80 minims). This preparation is used as a general and stomachic tonic and as a nerve and respiratory stimulant; for the latter, however, strych- nine is more effective. Strychninae sulphas. U.S.P. 1.5 mg. to 3 mg. (%0 to %o £r-)- Strychnia is injected subcutaneously in most emergencies to stimulate the reflex activity of the spinal cord, the respiratory cen- ter and the heart. Salicylates Sodii Salicylas U.S.P. Dose 1 gm. (15 gr.). Salicylates are given for the analgesic and slightly antiseptic action, especially in acute rheumatic fever, (Dock, George: The Physician and Surgeon, June, 1901), but also in acute pleurisy with effusion (Dock, George: Therapeutic Gazette, Feb. 15, 1893). The drug is usually given in gram doses every two hours until the pain is relieved. If the stomach is irritable and becomes in- tolerant of the drug, it may be given in a boiled starch enema with some opium preparation to allay peristalsis. As large doses as 10 gm. to 15 gm. (150 gr. to 225 gr.) can be given in this way. The administration of salicylates, especially in acute rheumatic fever, is accompanied by equal doses of sodium bicarbonate to lessen or prevent gastric irritation. The ingestion of large amounts of fluid is also of great value. Rest in bed and absolute rest of the affected joints, with splinting when it is necessary, is important. Methyl salicylate or oil of wintergreen and flannel bandages are applied to the joint and baking with an electric light bath is routinely employed with benefit to the patient. Acetyl salicylic acid, "aspirin" N.N.R. Dose .3 gm. to .6 gm. (5 to 10 grs.). 426 METHODS IN MEDICINE Aspirin is in vogue at present as a substitute for the other salicyl- ates because it passes through the stomach unchanged and is con- sequently unaccompanied by gastric symptoms. Atropin Atropinae sulphas U.S.P. Dose .4 mg. to 1.3 mg. (%so gr. to %o gr.). Atropin is injected subcutaneously as an antispasmodic, an auto- nomic system paralyzer, and a secretory depressant. Cardiospasm and pyloric spasm, bronchial asthma, vagotonia, partial heart block, and pulmonary edema are indications for the drug. Benzyl ben- zoate or succinate is being substituted in many instances where atropin is used as an antispasmodic. Tinctura Belladonnae U.S.P. is used in the treatment of drug and liquor addictions. Bromides Sodium bromidum U.S.P. Dose 4 gm. to 8 gm. (40 gr. to 120 gr.). Bromides by mouth are the most commonly used sedatives and cerebral depressants. They are unsurpassed in the quieting down of the nervous excitability of a hysterical family following the death of a relative. Car-sickness and sea-sickness respond well to bromide therapy. Insomnia should not be treated by the drug. Convulsions are relieved or aborted and consequently bromides are widely used in the treatment of epilepsy. Luminal is, however, replacing much of the bromide therapy in epilepsy. Chloral In the group of hypnotics and soporifics, chloral, trional or veronal are used interchangeably although the latter preparation is the more popular one. Chloralum Hydratum U.S.P. Dose 0.3 gm. to 1.3 gm. (5 gr. to 20 gr.). Chloral has been more or less neglected during the past few years. It is an excellent and powerful remedy for the relaxation of spasms as in strychnine poisoning and tetanus. It is a powerful hypnotic in insomnia from nervousness and in alcoholic delirium. dock's twenty drugs 427 Heart disease is considered a contraindication to its use in large doses especially. A habit may be acquired. Trional Sulphonethylmethanum U.S.P. Dose .2 gm. to 1 gm. (12 gr. to 15 gr.). Has no special advantages and may be habit-forming and in larger doses or after prolonged use hematoporphyrinuria accompanied by weakness, etc., appear. Veronal or Barbital N.N.R. Dose .3 gm. to .6 gm. (5 gr. to 10 gr.) is rapidly absorbed if dissolved before administering, but it is a rather slowly acting hypnotic. Large doses indiscriminately used may prove fatal. Ammonium Chloride Ammonii Chloridum U.S.P. Dose .3 gm. to 1 gm. (5 gr. to 15 gr.). Ammonium chloride is a quickly absorbed and active expectorant, which is quite generally used in acute bronchitis. The taste of the salt is disagreeable but it is well borne in a simple elixir to which some liquorice has been added (Elixir adjuvans). Other expectorants, the balsam of Tolu, or the syrup of Tolu, are used, for besides being stimulants and expectorants, they are pleasantly flavored vehicles for other expectorants. Terebenenum U.S.P. Dose .3 to .6 c.c. (5 to 10 minims). Terebene is a stimulating expectorant especially useful in the later stages of bronchitis, the late acute, subacute, and chronic stages. It is best given in a capsule or on sugar. In some cases a com- plicating gastrointestinal and renal irritation may result. Phenacetin Acetphenetidinum U.S.P. Dose .1 gm. to .3' gm. (1% to 5 gr.) sufficient. Plienacetin is analgesic and sedative for certain types of pain, such as dull aches, especially headaches, and migraine. It is also a sedative in car-sickness and sea-sickness. The analgesic effect is enhanced by the addition of caffeine in .1 gm. (1% gr.) doses. If small doses as those given are ineffective, large doses likewise fail to give relief. The drug in large doses produces cardiac depression and methae- 428 METHODS IN MEDICINE moglobinemia with cyanosis, though it does this with less frequency and more slowly than does acetanilid. Calomel Hydrargyri Chloridum Mite U.S.P. Dose 8 mg. to 16 mg. (% gr. to % gr.) given every 15 to 30 minutes for 4 to 8 doses totaling 65 mg. to 130 mg. (1 gr. to 2 gr.). Calomel is mild purgative which is considered by some to have an intestinal antiseptic action. It is used in the form of an oint- ment as a spirocheticide in prophylaxis and therapeusis. Saline cathartics are usually given the morning following the administration of calomel. Sodii sulphas U.S.P. Dose 10 gm. to 15 gm. (2 to 4 drams). Glauber's salt is the main constituent of Pluto or Abilena water. Magnesium sulphate, "Epsom salts," and Sodium phosphate are useful salines. Oleum Ricini U.S.P. Dose 15 c.c. to 60 c.c. (% oz. to 2 oz.). Castor oil should be fresh and not rancid and the necessity of disguising solutions will be unnecessary. It is a mild purgative with a subsequent constipating effect, which facts are made use of in the treatment of some forms of diarrhea. In pregnancy, a dose of castor oil may start labor pains. Fluidextract Cascarae Sagradae U.S.P. Dose 1 c.c. to 1.5 c.c. (15 to 25 minims) gradually decrease dose as action is secured. Cascara is a tonic laxative and should be used in small doses and it should never be administered as a purgative in doses of 4 c.c. to 8 c.c. The aromatic preparation is not uniform, is weak, and should consequently not be used. Bismuthi Subgallas U. S. P. Dose .3 gm. to 1 gm. (5 to 15 gr.). Bismuth is used for its mechanical effect chiefly, acting as an insoluble powder, coating over ulcerated areas in the stomach and bowel and exercising a slight astringent action at the same time. Violent and profuse watery diarrhea often respond favorably to bismuth. Bismuth dock's twenty drugs 429 Nitrites Spiritus Glycerylis Nitratis U.S.P. Dose .05 c.c. to .15 c.c. (% minims). Tabellae Trinitrini B.P. Dose .65 mg. (%00 gr.). Sodii Nitris U.S.P. Dose .06 gm. to .12 gm. (1 to 2 gr.). Nitrites are powerful vasodilators, but their effect is very fleeting. The paroxysms of angina pectoris are promptly relieved by amyl nitrite or nitroglycerin as is also cardiac embarrassment and espe- cially that with an accompanying hypertension. Acids and Antacids Acidum Hydrochloricum Dilution U.S.P. Dose 1 c.c. to 1.5 c.c. (15 m. to 25 minims) contains 10 per cent hydrochloric acid gas. Hydrochloric acid is used as a substitute when there is a de- ficiency of gastric acid secretion. To be effective, it must be given repeatedly in full doses every fifteen minutes after a meal for 4 to 6 doses. Diarrheas due to achylia respond well to the drug. Sodii Bicarbonatis U. S. P. Dose I gm. to 20 gm. (15 gr. to 30 gr.). Sodium bicarbonate is the most commonly used alkali. Magnesium Oxidum U.S.P. Dose .6 gm. to 3 gm. (10 gr. to 45 gr.). Heavy oxide of magnesium is the most powerful antacid, being four times as active as sodium bicarbonate and at the same time non-gas producing and mildly laxative. Likewise, it produces a very much smaller secondary increase in gastric secretion after the original neutralization than does sodium bicarbonate which is the most powerful stimulant to gastric secretion following neutraliza- tion. For these reasons the drug seems to be the preferable antacid (Hurst). If the laxative action becomes a troublesome factor, it may be controlled by bismuth subgallate or subcarbonate. Ipecac Ipecac U.S.P. Dose .65 mg. (1 gr.) as an expectorant often used in the form of Syrup of Ipecac in 1 c.c. (15 minim) doses. Ipecac is frequently used in children as an expectorant. The drug is rarely used as an emetic at present. 430 METHODS IN MEDICINE In amebic dysentery treatment (see p. 410) ipecac powder is given in salol or keratin coated pills in doses of 2 gm. to 8 gm. (30 gr. to 120 gr.) or through a duodenal tube, directly into the intestine in 10 gm. to 15 gm. (150 gr. to 225 gr.) doses. Emetine bismuth iodide in .65 mg. to .2 gm. doses to a total of 2.5 gm. (36 grs.) is preferred by English therapeutists. The intestinal medi- cation is often supplemented by subcutaneous injections of Emetine hydrochloride 3.2 mg. (% gr.) doses. Anthelmintics Oleoresina Aspidii U.S.P. Dose 2 gm. to 8 gm. (30 gr. to 120 gr.). Male fern is the generally used taeniacide for all types of tape- worms. (See Treatment of Taeniasis, p. 409.) Santonin U.S.P. Dose 65 mg. (1 gr.). Santonin is an active parasiticide for intestinal round worms, especially Ascaris lumbricoides. Thymol U.S.P. Dose .5 gm. per each 5 years of age to 3 gm. to 4 gm. (7.5 gr. to 60 gr.). Thymol is an active anthelmintic against hookworm infection, but it is being largely replaced by oil of chenopodium in ankylos- toma infection. Oleum Chenopodii U.S.P. 1.5 c.c. to 3 c.c. (20 m. to 45 m.). Oil of chenopodium is an active anthelmintic, especially against hookworm. The drug may be given through a duodenal tube and should always be followed in two hours by a saline purge. Opotherapy-Sera and Vaccines Adrenalin, Pituitrin and Thyroxin are powerful circulatory and general nonstriated muscular and nerve ending stimulants. They are used as substitutes in deficient secretion of the respec- tive glands which they represent. Temporary success alone is ob- tained with adrenalin in Addison's disease, while the results with pituitrin in pituitary disease are as yet not established. Thyroid extract, thyroxin, however, has a lasting effect on the basal metab- olism and is consequently very successful in the thyroid insuffi- ciencies. The desiccated thyroid gland, corpus luteum, pituitary body, ad- renal gland, thymus, ovary, testicle, etc., are prepared but only dock's twenty drugs 431 the first four have any definite physiologic effect. The endocrin- ology craze has gone far into pseudoscience. Sera of established therapeutic value: Toxin-Antitoxin Mixture: For active immunization against diphtheria, in- ject 1 c.c. subcutaneously for 3 doses, at intervals of two weeks. Repeat Schick test. Desensitization: Test sensitiveness to horse serum with an injection of 0.02 c.c. of a 1/10 solution in normal saline intradermally. If positive, within an hour an urticarial wheal with a surrounding erythema will appear. Desensitize by the subcutaneous injection at 30 minute intervals of 0.25 c.c., 0.50 c.c., 1.0 c.c., 5.0 c.c., and 10.0 c.c. of 1/10 solution of horse serum in normal saline. The same doses may then be given intravenously1 or after i/> hour pro- ceed with the antitoxin subcutaneously, injecting the first c.c. slowly, and then waiting several minutes. The intravenous injection can then be made. Adrenalin should always be at hand to combat anaphylaxis. Serum Antidiphtiiericum : For passive immunization give 1000 to 2000 units. For active diphtheria give 10,000 units subcutaneously and 10,000 units intravenously. In nasal or laryngeal diphtheria or very virulent cases, dosage is run up to 100,000 units. Serum Antitetanicum : For prophylaxis give 1500 units intramuscularly. For therapeusis, give up to 5000 units intrathecally, intravenously and locally. Serum Antibotulinicum : Give both TYPE "A" and TYPE " B" intra- venously in one large dose of at least 20,000 units as soon as possible. Obtain- able from PROF. ROBT. GRAHAM, University of Illinois, Urbana, Illinois. Serum Antimeningococcicum : Give intravenous and intrathecal injections of 90 c.c. every* 8 hours. Skull trephining and intraventricular injection is often in- dicated. Serum Antipneumococcicum (Type I) : Give intravenous injections of 100 c.c. every 8 hours until the fever is below 102°F. Vaccines: Virus Vaccinicum : Clean skin over deltoid insertion with acetone. Scarify skin, drawing serum but not blood. Apply fresh glycerinated virus and allow to dry. The virus may* be injected intradermally. Vaccinia Typhosum : Containing besides killed B. Typhoid B. paratyphoid A and B. Inject subcutaneously between the scapulae or over the triceps, one c.c. containing respectively 500, 1,000, and 1,000 million bacilli at 7 to 10 day intervals for three doses. For use as Foreign Protein, give dilutions beginning with 100 million. Vaccinia Staphylococcicum, Streptococcicum and Autogenous Vaccines usually contain 500 million organisms per c.c. It is often advisable to begin with dilutions of 50 million and increasing daily by 50 million to 500' million, which dose is then given every third or fifth day. PART V RECORDING, GRAPHIC AND CHARTING METHODS COMPOSITE HISTORY WITH ALL STANDARD TYPICAL CHARTS CHAPTER XXX THE HISTORY IN ORDER Front Sheets Body of History Regular History Sheets Rubber Stamps in Margin to call attention to special notes on Special Procedures, etc. Anatomical Outlines for recording all regional abnormalities (Charts or Rubber Stamps obtainable from The American Medical Association). Charts, etc., in the histories are to be arranged in the following order: Pink Sheets-Routine Blood Sheet. Green Sheets-Routine Sputum, Gastric Contents, Stool and General Pathological Report Sheet. Special Blood Charts Anemia Chart Leukemia Chart Blood Pressure Chart Apex, Radial and Deficit Chart, for recording graphically Digi- talis Effect. Vital Capacity Chart, with Fluid Intake and Output and Weight Curves. Cardiograms Cardiac Charts 432 THE HISTORY IN ORDER 433 Gastric Analysis Charts Gastric Carcinoma Chart, with moderately severe pyloric ob- struction. Gastric Ulcer Chart, with slight pyloric obstruction. Rehfuss and Gorham Methods. Duodenal Analysis Chart, for Gall Bladder Diagnostic Pro- cedure and Duodenal Pigment Estimation. White Urine Sheets-for recording data on 12 hourly urine Specimens. Special Urine Charts Cardiorenal 12 Hour Intake and Output Chart Two Hourly Renal Test Chart Metabolism Charts Food, Urine, and Blood Findings in a Severe Diabetic Diet Chart-Food Values for the same patient Diabetic Chart Sugar Tolerance Charts Blood Sugar Curves-Normal, Myxedema, Exophthalmic Goitre, and Chronic Pancreatitis. Blood Sugar Curves-Renal Diabetes, Hypothyroidism, Froh- lich's Syndrome, Neurasthenia, Acromegaly, and Diabetes Mellitus. Basal Metabolism Chart Adrenalin Chart Pilocarpin Chart Atropin Chart Cerebrospinal Fluid Chart Paretic Curve Tabetic Curve Visual Fields Chart Vestibular Tests Chart X-ray Reports Complete G-I Report, Case of Carcinoma of the Stomach with G-I Orthodiagram. Dental Report Hydrotherapy Report Treatment Sheets Occupational Therapy Nurses' Notes and Nurses' Charts 434 METHODS IN MEDICINE Graphic (Pulse, Temperature, and Respiration) Chart including spaces for all therapeutic orders Letters according to date including all correspondence concern- ing the patient Ward Charts Diet List Measurement of Urine Movements Narcotic Report Death Report Refer Blanks, Wassermann Request, Clinical Pathology, X-ray Requisition, Prescription Blank, Hydrotherapy Request, Cer- tificate of Release, Transfer Notice, Report to Home Doctor. 435 THE HISTORY IN ORDER FRONT PAGE* BARNES HOSPITAL 99991 Madkal H«. 45389 WARD1418 RJmSK Married XK\SMtKK X Name DeLuberduke, Leah DeFrance.. Age. .. 48 SexJemale... Address North Fifth Ave., Vandalia, Ill. Race White Occupation i/.® - - Nationality ....V.-.Sj A. Relative ....?.i°hard B. peLub.e.rduke How Related Hu.e.bftn.4.... Physician ..Dr. tA-L-.T.-.. Williams Address.. Fifth..AYe..4..Vandaliaa.lll.t. Admitted . J.VAX..Ki.. Discharged.... .^.^.P.t.ember __15 -1921 History Taken by... Result D.ip.d-Aylt.OjaSy . DIAGNOSIS: 79A V.D.C.C.(Mitral Stenosis & Insufficiency); u 1 79C Auricular r'iorillation; 79u Auricular Flutter; " 79C- Hypertrophy of Heart; 79C Dilatation,Cnronic Cardiac; TT J 79C Cardiac Decompensation(moderate); Z 0 98 Hydrothorax (R.). i FORMER AND SUBSEQUENT ADMISSIONS Date of Admission and Discharge Service No. Diagnosis ! Jan.1,'17-Feb.25,'17 25311 V.D.C.C(Mitral Stenosis*: Insufficiency) 3 Cardiac Decompensation( moderate). 8 Sep.15,'18-0ct.l.'18 36411 V.D.C.C.(Mitral Stenosis & Ipsuff ic.iencv 4 Auricular fibrillation: Cardiac uecomoensationCmoderate).Aohasia 5 Oct.l,'19-Nov.20,'19 40511 V.D.C.C.(Mitral Stenosis , - 6 Auricular Fibrillation; Cardiac Decompensation. ~ REMARKS 7/1/21 Blood Wassermann-Negative(7/3/21) 7/1/21 P.S.Phthalein let hr. 2nd hr. = total 30< 7/1/21 Blood culture negative (7/8/21) 7/1/21 Blood N.P.N. = 53 mg. per ion on. 7/2/21 Widal Negative in Dil. 1 -50 7/2/21 Snutum Culture-Strep, hemolvticus (7/5/21) 7/3/21 Heart (Plate at 7 ft. 7/9/21 Quinidine .1G. then .4 G t.i.d. 7/3/21 Electrocardiogram- Aur. Fib. 7/10/21 Electrocardiogram-impure A.F 7/4/21 Thoracentesis 800 cc. transudate 7/4/21 Karell diet & Hay Cone. Salts.. 7/5/21 Massive dose tinct. Digitalis (18 cc.) 7/6/21 Theocin .2 G. at 8, 10 & 12 o'clonk 7/6/21 P.S.Phthalein 55% in 2 hrs. 7/12/21 Electro cardiogram-ndruial Tote: The history sheets are all of standard letter size, that is 8x11 % inches. 436 METHODS IN MEDICINE HISTORY SHEET BARNES HOSPITAL MEDICAL NO Name P. S. Phthalein* Consultation Cultures Widal Test Tolerance Tracings Salvarsan UJ Pho'o 0 Z -I Z X-ray I m Summary by Asst. Res. Dental Examina- tion Electrocard io- grams Paracentesis Lumbar Puncture "Marginal stamps to be used in histories to call attention to special notes and special procedures and the results of the same. A set of these rubber stamps is kept on each ward. Others besides those shown in mar- gin are as follows: Complement Fixation Test-Nonprotein Nitrogen- 2 Hourly Renal Test-Concentration Diuresis Test-Diuresis Observa- tions-Massive Dose Digitalis-Pharmacologic Tests-Sensitization Tests -Blood Culture-Basal Metabolism-Special Procedure-Transfer Note > -Discharge Note-Surgical Note-Autopsy Note. 1-20, 10M. Form 40, | THE HISTORY IN ORDER 437 ANATOMIC OUTLINES FOR DIAGRAMMING REGIONAL ABNORMALITIES A set of rubber stamps of these forms is kept on each ward and the one best representing the region of the lesion, is selected and stamped on the history sheet along with the physical examination, and the abnormality sketched in the diagram. Various forms) shown on history sheets following. Dr. R. W. Mills' Anatomic Outlines Conforming to Habitus Types. Asthenic. Hypersthenic. Certain of the visceral topograph- ical peculiarities of the hypersthenic, a dominant major type, are here indi- cated in an orthodiagraphic visceral study. The visceral peculiarities of the hypersthenic are a high digestive plant of great tonus, a transverse heart, lung fields broad at the base narrowing to the apex and antero- posteriorly deep. A rapid alimentary motility is also characteristic. The visceral form and arrangement of the asthenic, a dominant major type. The visceral characteristics of the asthenic are a low digestive plant of poor tonus and Slow motility. The heart is vertical, the lung fields long and widest in their upper zones. Vis- ceral topography and form as here shown are very apparently determined by bodily proportions and regional capacities. Special attention is di- rected to the disharmonically wide and capacious pelvis, the distance between the anterior iliac spines being actually greater than in the hypersthenic sub- ject. 438 METHODS IN MEDICINE Dr. R. W. Mills' Anatomic Outlines Conforming to Habitus Types. Hyposthenic. Sthenic Certain of the visceral peculiarities of the hyposthenic are here shown in an orthodiagraphic study. The thorax being moderately long, the lung fields are intermediate in their general pro- portions. The heart is pendent resem- bling that of the asthenic. The stomach and other alimentary viscera are moderately low, though less so than in the asthenic, chiefly on account of the larger pelvis of the latter. Vis- ceral tonus is rather poor and motility of average rate. Certain of the visceral peculiarities of the sthenic are here indicated. The drawing is an orthodiagraphic study. The thorax being relatively short, the lung fields are widest at the base ; the heart moderately transverse. The ab- domen is rather long, its viscera moderately high in keeping with the abdominal regional capacities. Tonus is marked and alimentary motility more rapid than the average. THE HISTORY IN ORDER 439 BARNES HOSPITAL MEDICAL NO Name BINDING LINE 1-20. 10M. Form 40. The reverse side of these charts is printed the same as the obverse side shown above. 440 METHODS IN MEDICINE BARNES HOSPITAL MEDICAL NO Name BINDING LINE 1-20. 10M. Form -10. THE HISTORY IN ORDER 441 BARNES HOSPITAL MEDICAL NO Name BINDING LINE 1-20. 10M. Form 40. 442 METHODS IN MEDICINE BARNES HOSPITAL MEDICAL NO 1 Name_ BINDING LINE 1-20. 10M. Form 40. THE HISTORY IN ORDER 443 BARNES HOSPITAL MEDICAL NO Name BINDING LINE 1-20. 10M. Form 40. 444 METHODS IN MEDICINE BARNES HOSPITAL MEDICAL No Name BINDING LINE 1-20. 10M. Form JO. THE HISTORY IN ORDER 445 BARNES HOSPITAL MEDICAL NO Name BINDING LINE 1-20. 10M. Form 40. 446 METHODS IN MEDICINE BARNES HOSPITAL MEDICAL No Name BINDING LINE 1-20. 10M. Form 40. THE HISTORY IN ORDER 447 BARNES HOSPITAL Name MEDICAL NO BINDING LINE 1-20. 10M. Form 40. 448 METHODS IN MEDICINE THE PINK SHEET BARNES HOSPITAL ReglsterNo Medical No N aine W ard BINDING LINE URINE DATE Amount C.C CHARACTER Specific R Gravity action Sugat Albumin MICROSCOPICAL EXAMINATION REMARKS SPECIAL TEST BLOOD DATE . FRESH BLOOD RED BLOOD CELLS WHITE BLOOD CELLS Hemo- globin Index REMARKS DIFFERENTIAL COUNT DATE No ol Cells Counted J E C j l ii i? £z hi a 2 J 5 S Z fl J c | 2 8 | | 1 DATE Blood Culture 1 Per cent Number of Cells Absolute Number p" Number of Cells Absolute Number STAIN USED PATHOLOGICAL CHANGES IN THE BLOOD EXAMINED BY ■ Form ST 1UM H IM Obvers-e side 449 THE HISTORY IN ORDER BARNES HOSPITAL No Name Ward BLOOD DIFFERENTIAL COUNT g o 2 X s 11 J? 2 •f. a Myelocytes Eosinophilic ■g i 3 ! 2 loll j DATE RED BLOOD' CELLS "WHITE BLOOD CELLS globin t -J £ O Zz E 5 c s i •2 1 j 1 ; Is Reverse side 450 METHODS IN MEDICINE THE GREEN SHEET Form 6!*. UM. 1-17-1. BARNES HOSPITAL REGISTER NO MEDICAL NO NAM E W ARD SPUTUM DATE c. c Consistency Character Bacilli Elastic Tiriue Blond Bacilli REMARKS STOMACH ANALYSIS DATE Character of Test Meal Recovered Time in Character Mucu, Blood Free H Cl (Deficit?) Acidity Acid REMARKS STOOLS DATE Amount Comirtency Color (Pigments) Mucuo Blood Pun Microscopic (Parasites or Ova) REMARKS PATHOLOGICAL REPORT Obverse side THE HISTORY IN ORDER 451 BARNES HOSPITAL MEDICAL NO LABORATORY RECORD OF FRACTIONAL GASTRIC ANALYSIS Date Age Name No. Diagnoses: Tentative. X Ray. Final. Habitus: Hypersthenic Sthenic Hyposthenic Asthenic Preparation: Fasting, thirsting, for hrs. Remark Fasting Contents: Total ccm. Fluids ccm. Sediment ccm. 80 Float ccm. _o Characteristics * Color Mucus . ' M Food Microscopic Blood . to Cells ' Bacteria Starch . ") Yeast - . , Sarcinae Muscle fibers Occult blood " 20 ( Feces-occult blood 30 I FC IS JO 15 I hr 15 !■» 45 ?hrs Test meal given at A. M., finished at A. M. Kind. Method Titrations. Characteristics. Amt. - HCI. + HCI. Total Acid. Ph Am t Used. Contents. 15 min. 30 min. 45 min. 1 hr. 15 mm. 30 min. 45 min. 2 hrs. Reverse side 452 METHODS IN MEDICINE \ F EE S S M n This standard cross section paper is used for making all types of special charts for Barnes Hospital Histories. * j 453 THE HISTORY IN ORDER 454 METHODS IN MEDICINE THE HISTORY IN ORDER 455 '■Tame BARNES HOSPITAL BLOOD PRESSURE CHART SERVICE Ward- NO - Date Hour B P MM HG 240 230 220 210 200 190 UJ 180 z j 170 0 Z_| 160 0 2 150 (D 140 130 120 110 1OO 90 80 70 60 50 40 • Systolic o Diastolic Apparatus - - 1 l-JLB. Fotm 41 456 METHODS IN MEDICINE THE HISTORY IN ORDER 457 458 METHODS IN MEDICINE HEART STATION WASHINGTON UNIVERSITY MEDICAL SCHOOL Name No. Date Record No. Curves made: Show Space for curves THE HISTORY IN ORDER 459 HEART STATION WASHINGTON UNIVERSITY MEDICAL SCHOOL Name N°-14638 Date 1/30/20.12:11. Record No. 3493 Curves made: 1,11,111* Show Normal electrocardiogram. Bradycardia (sinus) Rate 56 "QRS" guoup lead III short and split up. "T" inverted in lead III. George .Herrmann, Space for curves 460 METHODS IN MEDICINE HEART STATION WASHINGTON UNIVERSITY MEDICAL SCHOOL Name JWWW.CMH. No. 13530 Date 10/2E/19.5; 30pn> Record No. 3064 Curves made : 1,11 , 111 . Show Right branch bundle block. Auricular fibrillation. Rate 160 F.ff .Wilson . Space for curves THE HISTORY IN ORDER 461 BARNES HOSPITAL CARDIAC CHART MEDICAL NO_ Name Age Ht Wt ETIOLOGY Rheumatic Fever Chorea Tonsillitis, Acute (repeated) Scarlet Fever Diphtheria Other Infections Blood Culture SyphilisWassermann Toxic Goitre ArteriesB. P : Sys.Dias. Kidneys EXAMINATION Apex Beat _ Abnormal Pulsation Signs of Aneurysm i,, Thrills Z ~ Shocks Pulse Q Vascular Signs m Size of HeartPercussion RIA X-Ray MRMLAL .Modified Sounds Murmurs function K/4? Cecity Dyspnoea Cyanosis Net* Yeins IjVerLungaEdema Cardiac Pain ElectrocardiogramRateP-RQRStRemarks No. Digitalis Cardiac Diagnosis 6 20 IM Korn 29 462 METHODS IN MEDICINE CARDIAC CHART NAME OCCUPATION ADDRESS (Surname) (Christian Name) (Initial) XO Date Age Sex.. -- Color . S. M. W. Local M. D- ETIOLOGY: (History I CLINICAL FINDINGS: (Physical Examination) F. H P E Ht Wt T P _R Nutrition Cardiac Disease (type and results) Position Dyspnoea Cyanosis Vascular Disease - Eyes - Pupils Teeth Congenital Syphilis Sinuses ... Tonsils . Fundi Miscarriage* .. . -* Glands Thyroid Tracheal Tug P. Ha - - - Neck Veins ■ , ,, Carotids Subclavians Rheumatic Fever .. .,. - Aortic Arch in Suprasternal Nntrh Chorea . . ■ Heart: Abnormal Pulsations Tonsillitis Acute (repeated) . - , - Ap<x beat - Signs of Aneurism .. Scarlet Fever . ; Tnrills ._ ...... Shocks ; Diphtheria - . Dullness Orthodiagram or Habitus Tnflnenya R-MSL-L. Teleroentgenogram Cardiac Angle - Pneumonia - Trs rm MP Heart Rate, Rhythm and Sounds __ Venereal Disease - - I -.ML - ... -- - . Other Infections ■ II ... A , Murmurs Toxic Goitre - III ■ Long. - --- Arteriosclerosis , - --,IV .Ob) -- - - ■.,. ■ Nephritis . --- V - . - POD% - Habits: Coffee and Tea Tobacco. Alcohol, . - VI A|V FUNCTION: (Symptoms) P I Chief Complaint. . Vascular Signs Onset (Symptoms and Date) -■ Pulse-. . - Deficit Palpitation . - Arteries' B. P Sys Dias Dyspnoea- Lungs V ital Capacity Pain Abdomen . . Tenderness Ascites. ,, Cough . • Liver Spleen Nausea and Vomiting --. Extremities- Cyanosis Oedema Clubbing Nocturia . . . . _ Urine' Sp Gr Alb Glu Casts ■ ,, - -■> Rbc Other Symptoms. - " ■ - P S. P -.- - - ■ - ■ Oedema _ - ■. Blood • Wasscrmann Culture N. P. N B U. N Bl. U. Jaundice. . Hb Rbc Wbc Differential. . - . . , . ■ , Syncope DIAGNOSIS (etiological, anatomical and functional) Attacks ■ ■ ---- CAPACITY for Work Previous Treatment - ■ Form 2l"2(2-6-22)lM Obverse side 463 THE HISTORY IN ORDER No. Date Rate P. R. QRS REMARKS TREATMENT | RESULT NAME (Surname) (Christian Name) No. Service ELECTROCARDIOGRAMS Keve rse side 464 METHODS IN MEDICINE THE HISTORY IN ORDER 465 466 METHODS IN MEDICINE 467 THE HISTORY IN ORDER 468 METHODS IN MEDICINE IU Z J 0 z Q Z cd BARNES HOSPITAL URINARY CHART skvice no Name Ward A d m i tied DATES AMOUNT C. C. CHARACTERISTICS SPECIFIC GRAVITY REACTION SUGAR ALBUMIN SEDIMENT MICROSCOPICAL EXAMINATION REMARKS 11-19- 6M Form 60. THE HISTORY IN ORDER 469 470 METHODS IN MEDICINE THE HISTORY IN ORDER 471 BARNES HOSPITAL BINDING LINE Date 472 METHODS IN MEDICINE BINDING LINE BARNES HOSPITAL MEDICAL NO- N apic WEIGHTS IN GRAMS FOOD PROTEIN FAT CARBO- HYDRATE CALORIES 6-20. 2 Obverse side H Form 12? THE HISTORY IN ORDER 473 weights in grams ro z 0 z Q r z POOD PROTEIN FAT HYDRATE CALORIES Reverse side 474 METHODS IN MEDICINE 4",MF"m4 BARNES HOSPITAL BINDING LINE M7?/ME 78X80)27 •z » 3 w S'* ><3 !i|. Ml S; 2- z k N£> Date J fXMS SMS 73tr (mj. C/7Z7.B. Ml. CM. ZKWtB zzzzzz ftrrp/fC ,wr: Wtti ?/- WS7/C PC/2] Y/ffiff&y /SrM WMH1 "xoAf//y//>f Off/WC JO OPS SPf-PP a, CO,. Cti.% 7%r % 2UK C0t, &oz>r Mr/fJ? /00 98 60 /#£ 2860 23Z 22/3 .33 36 rz 28 Z' 38 3rtA: /2./f. /■2ffS: 2720 xx 23" 70 2/W oy t-fff 3/3' WO /.3/. %90 36. k. 2/0 /.o 6/ 29% /%0 30.3 r/f 2.22 22 282 2960 32 2.6 26.7 0. 72 2306 2330 J9% /// 2.09 /22 .9 2070 z% fa X. X/ Z366 Z0Z3 30% zz Z.OX 28 /.O6 2230 % zt /6.7 3 7/ zxox 29.6 // 223 OS' .92 /620 Z6 /6% 3 72 206/ Z/M 23% o 2X0 22 239 2220 733Oj 6/.M 23 XX 2% Z03 /2% /W 23% o /W 233 22 930 %2_ /.3 Xl 72' W.S /Zf.3 'M> /Z7 O 2?2 <268 .fox rt 23 XX 2.62 ZO.S W.3 %/0 2/6 3 /Z? 6.03 .33 Art /SOOi ■ft!/ /% £2 ZS ?fa W.3 2/03 //■? t /%% 3038 278 % zwt f COO! w> ft fpp/rff <CS 2290 32/ 3 2-33 6.30 /■ 33 AAA fa. 7*f/C. f '■CP fk rs /Xoo 29. ff- 3.33 0.90 206 fa f C<>t rsp ft US //20 /?. rtf 273 6.2/ 223' 2360 'TTZSs fa /W/t C Oe>t ■•ocp J 'CFS/J. vers 22% rtf 232 72? 2.0% 2330 C7O/& fa f. 30.3 Zo/z 20- frt 2% 20? 2X2 2900 2 30.3 Zo/.Z 2W 36. rtrt 0.63 2.6? 3230 fa x 30.3 Xo/.Z 2033 %3. rtrt 3.3? ?63 Ztt 3320 fa X 30.3 zo/z 20/3 rtff A? 222 273 X9% 3?./ /XC/O5 THE HISTORY IN ORDER 475 Form 122 10-16-L BARNES HOSPITAL O/r777&7>7/<' SS/S777/77 CSZTrr register no. soazi r/U42s ooqQq ti fmtZO«r*<r/rre / (S/SS Mme Seri/Si) medical ho..°7 ✓ ? 7 ,_ WEIGHTS IN GRAMS FOOD 8/">? // 6W 7orOi PROTEIN HYDRATE CALORIES ossrTfz/rr/n/Y S/rr zs 2S z SL 4 8 e5 0 Stt /OO /OO /? S /O 0 ////<•/ 700 /0O 8 ? ✓/ < j&STTZVf 8 /0 70 28 0 22 8. s 0 C?rfS7/>1 20 20 20 60 / SZ. 0_ £ 2 S7//7A' 7 00 /OO /? 2 /2 ? 0 0 MW SO so 8 7 70. s z? 0 corr/rff /wzsz 7S 2S /S S 2 3. ? AST-TM/T 20 . zs 3_ 0_ SO S0 ? 0 7 z' SWSSAiS W7//7S /OO /OO s ? /. / 0 8 /ZSS s 3S 8 /0. 2 Sr-Ztev/AS /OO ZOO. 7. / / 3 W77/7 /oo /OO 0' 7? 0 /SO /so SO/L 0. 0 0 0 22F SOr/72 so so /OO _zs S 3_ 0 0 Za/defTO 7S szs 3 3 ? Xf/vo/x zr//rr £S . so 0 0 s $ /00.3 '6 00. /SJO 0 fw/rj/rr 7W4n>/c) /oo /OO / 2 2 7 Cx/zxy 700 /OO f' / 8 7277/772 so fn K z / Ta/wrza/S) 700 /OO 2_ 7 7 3 C2i/i/2<7)/28 700 /OO /■ 8 J" 7 > sr. peso's /OO zao / 7 7 SsFS??2f2J 70/) 700 / 2. 7 ff ? 20 7 /Z&.0 /zry/yZz/ F, 2 /, 8 80 0 SSTZ/ZS//.,# f St. XzW'SXiOSS 7/ d 6/ Stuz/V Soy 7-} fflMJSirr'Tvai'i/rS or /ss J/£f£r*34*J 2. _//L 7~ 8. S7 ZSOO 7M7/// 7DM/> rsfr/tlU. 476 METHODS IN MEDICINE 477 THE HISTORY IN ORDER 478 METHODS IN MEDICINE 479 THE HISTORY IN ORDER 480 METHODS IN MEDICINE BARNES HOSPITAL /w/%3a/c mwt- Cfwrr HI„eMN,. />Z7Z>V rTteWsvCWc) ■ Case No. A- - Name Barometer mm. Log. Fact. Gasom . . .. .309 6 Samp Set. Tempo. Gasom °C. Log. Gasom diff Log Total vent (add) | End cm. cm. Log. Time. Log Vent, per min.. , . ■(sub) L. (.Diff ... (sub.) cm. cm. Log. % Oi absorbed . . Log. Oj Absorbed . (add) Duration of test m s. - min. Log. Total Cal. per.hr....(add) Cal. COj Expired % Log Surface area CCh Inspired 0.04% Log Cal. per. sq m. hr. (sub) Cal. COi Produced . .(sub.) % Oj Inspired, corn.. % Cal per sq. m hr (above nor ) Oj Expired % Cal. per sq. m. hr. normal 0: Absorbed , (sub.) % W z Difference. .... • (sub) J Log. difference 0 z Log. % COj produced. Log normal 0 Log. % Oi absorbed.. Log B M R. %. (sub) z 00 Log- Reap. Quot. *X- . ..(sub.) B M. R. Analysis by • Haldane No Analysis by • Haldane No. • Avg. co. % Avg 0<- % CO.H-0. Reading by: CflecKed by: Calculations by: Log. COi diff Log. Oz diff. Log. do, diff Log. O3 diff. First check by: Log. sample. -Log. sample Log. sample.- Log. sample - Second checfc by: Log. COi %. Log. 0: %... Log. CO, %. Log. Oi %... I co. % o. % CO. % Oi % Notes: THE HISTORY IN ORDER 481 BINDING LINE CEREBROSPINAL FLUID EXAMINATION Name Age Ward ■. Date Clinical Diagnosis Physician PRESSURE AMOUNT PHYSICAL . PROPERTIES CELLS PER C. M M. DIPP. CELL COUNT PROTEIN TESTS WASSERMANN LYMPH POLYS. ENOOTH. PANDY KAPLAN- ■ LOOO C S. P. COLLOIDAL GOLD REACTION MASTIC REACTION REGISTRY NO. TUBE NUMBER REGISTRY NO. REACTION TUBE NUMBER BARNES 1 2 3 4 5 6 7 8 9 IO 1 2 3 4 5 6 7 8 9 IO 5 CLEAR 4 COMPL PRECIP. 4 Pale blue 3 MARKED PRECIP. 3 BLUE 2 DISTINCT PRECIP. 2 violet 1 SLIGHT PRECIP. 1 Red-Blue O NO PRECIP. O Red _L Smears Quantitative Dextrose u BACTERIOLOGICAL EXAMINATION Culture ---- Animal Inoculation- - > ADDITIONAL CHEMICAL EXAMINATION f" Quantitative Protein Quantitative Chlorides OTHER EXAMINATIONS n O 2 J> Examined By 9-19. IM. Form S3. 482 METHODS IN MEDICINE BARNES HOSPITAL / y/zf'Z-Z/f service no. & 7&Q . lumbar puncture BINDING LINE CEREBROSPINAL FLUID EXAMINATION Name --Z Age Ward g T fl?//?S!7 - ? d Clinical Diagnosis ~/='7/:S tS'eA'h/'/f S PRESSURE AMOUNT PHYSICAL PROPERTIES CELLS PER C. M M. DIFF. CELL COUNT PROTEIN TESTS WASSERMANN LYM*H POLYS. ENOOTM. PANDY KAPLAN BLOOD > C S. F. 'Ptoirri'li /$c.C Z7/7F/P efxaf/x-'ss 7-/Z r//z BACTERIOLOGICAL EXAMINATION Smears Culture - Animal Inoculation-* - ADDITIONAL CHEMICAL EXAMINATION Quantitative Dextrose Quantitative Protein Quantitative Chlorides OTHER EXAMINATIONS -7 y?'Y& Examined By- Jwfs/7 S/yr/tr-#// /'fp »-l». 1M. Form R2. THE HISTORY IN ORDER 483 . ( BARNES HOSPITAL ///e BINDING LINE CEREBROSPINAL FLUID EXAMINATION Name- Age-32 Ward ? ~ Clinical Diagnosis Z^'S Physician■ PRESSURE AMOUNT PROPERTIES CELLS PER C. M M. DIFF. CELL COUNT PROTEIN TESTS WASSERMANN LYMPH POLYS. ENDOTH. PANDY KAPLAN BLOOD C 8. F HOct exe/fjf 7 E? /e/ffS? 7 Z<> BACTERIOLOGICAL EXAMINATION Smears -Culture Animal Inoculation ADDITIONAL CHEMICAL EXAMINATION ,<. QtrafrtTtJit+ve Dextrose TLL Quantitative Protein Quantitative Chlorides OTHER EXAMINATIONS Examined By -/rf- 9-19. 1M. Form 62. 7. O b < Id C □ o 0 Q O 8 484 METHODS IN MEDICINE The eccentric continuous /me indicates the average normat'.Field ofTiidirccll/sianslhe smalt circle the position ofthe blind spot. .Designed for use with ThofiJ/f/fardg's Hcpfsterinp ftnmeter. "Centre ca.ch chart with "prointer "at Zero before comnienci'/iy la use the ululonuzlic TteipTslratum'.' LEFT RIGHT PERIMETER CHARTS THE HISTORY IN ORDER 485 BARNES HOSPITAL VESTIBULAR TESTS SERVICC NO Name ■ ■ Nystagmus Looking Forward Looking to Right Looking to Left Looking Up Looking Down SPONTANEOUS Poi Right Shoulder from Above Shoulder from Below Shoulder from Side Elbow Wrist iting Left Summary <; Romberg Turning Head to R. Turning Head to L. Past-pointing Attempt to Overthrow Falling Goniometer To Right Amp. Duration Sec. TURNING To Right Shoulder from Above to to W Summary z J Nystagmus Vertigo Past-pointing Falling 0 To Left Z Amp. □ Duration Sec. To Left Shoulder from Above to to z ID Summary Nystagmus | Vertigo i Past-pointin Falling Douche Right Amp. After Min. Sec. CALORIC Douche Right Shoulder from Above to to Summary Nystagmus Vertigo Past-pointing i Falling Head Back Head Back Shoulder from Above to to Douche Left Amp. After M»n. Sec. Douche Left Shoulder from Above to to Summary [ Nystagmus 1 Vertigo Past-pointing 1 Falling Head Bach Head Back Shoulder from Above to 8-19. IM. rora 82. Obverse side to 486 METHODS IN MEDICINE (A D EARS< (A. S. (A D Fistula Test! 'a S Hearing Tests A D \_A A C< AC BC N Galt. Pol. AS. A A C< AC BC N Galt. Pol. NOSE THROAT HISTORY m z o z o r Z m SUMMARY DIAGNO1S Reverse side THE HISTORY IN ORDER 487 Rating of Exam. X-RAY EXAMINATION REPORT Page No Exam. .. Name - - Case..... Plates- Habitus..... " -- Notable findings: Date... Exam. 1st. Fluor. X-Ray Diagnosis Clinical Diagnosis Operative Confirmation 488 METHODS IN MEDICINE 29-F-W-M. Rating of Exam. 3-Grtho. photo., fib. recumbent. X-RAY EXAMINATION REPORT Pagel. No. 2110 Exam... Name CMBV, R. S'. D. #■, Mo. Case (3) Barnes Hosp.,(Surg. ) piates Habitus Disharmonic, tending to " Asthenic to Hyposthenic Notable findings: Date ._ April 19th, 1920.. . „ Exam. 1st. Fluor. 1. Stomach does not correspond to habitus; higher and more tonic than would anticipate. (a) influencing; Oarcinoma ventriculi. 2. Gastric motor insufficiency, organic, (1°). (a) Strangely good gastric motility consider- ing extent of prepyloric defect and lack of initial gastric motility. 3. •'filling defect involving entire distal four-fifths of pars pylorica. defect extensive, annular, obliterative; in itself, rather characteristic of carcinoma. However, unusual that lumen through involved part not more defin- itely shown - especially in view of comparatively prompt fastric motility. a) Palpable mass in part registers with prepyloric defect, but, strangely, witn distal portion of defect only. (Possibility that involved liver overlaps posterior gastric tumor.) Gonsi(ier: 4. Great palpable mass occupying nearly entire upper half of abdomen, its area corresponding to that of moderately enlarged liver. Mass of strikingly irregular edge and surface, the latter very unevenly lobulated. 5. Tenderness, right central epigastrium, (1°); rather localized, not very marked - registers over portion of enlarged liver. 6. (Note) Special enema in effort to determine whether trans, colon involved in mass suggests that such free. SURGICAL TOPOGRAPHICAL NOTE,- Tumor probably inoperable. Gastric motility good, in spite of involvement. Gastroenterostomy hardly indicated. Stomach high and behind involved liver. Any resective or anastomotic procedure will be dif- ficult. --X-Ray Diagnosis- Tumor involving entire pars Clinical Diagnosis pylorica, (carcinoma 60), with secondary involvement of liver (60). Gastric motor insufficiency, organic (1°)• Operative Confirmation THE HISTORY IN ORDER 489 Rating of Exam. X-RAY EXAMINATION REPORT Page Z. No. Exam. Name .VjRMMMH ..GMHS, Case Plates . .. Habitus . . ._ .. . " --- , , . April 19th,1920 Notable findings: Contfrom pg.l. Uate - Exam. 1st. Fluor. 10:45 A.M. " 2nd " 5:30 P.M. BISMUTH AND WATER (6$hrs.) 1. No initial clearance. 2. On palpation, none. 3. Later palpation, slight initial clearance (?). 4. Cap not visualized. 5. Ring not visualized. B. & W. Second duo. not visualized. Gastric tonus, poor. 6. Peristalsis. Pyloric tonus, overgood; Initial pylorospasmf?). BARIUM AND PERMILLAC 1. No initial clearance. B. & P. 2. On palpation, none. Gastric tonus, overgood. 3. Later palpation, initial clear- Pyloric tonus, overgood, ance (1); duo. only; active; canalization fairly easy. 4. Cap visualized(?). 5. Ring not visualized. - Second duo. good. 6. Peristalsis (3). At 6* hours, stomach small amount (1). At 6* hours, small intestine, cecum (slight). Plates: - Stom., 8x10 (a) " 8x10 (a) " 8x10 (ab) " 10x12 (ab) 6fhrs. 11x14 (a) 24 " 1Dx12 (ab) 48 " no plate made. Ba.En. " " " X-Ray Diagnosis Clinical Diagnosis Operative Confirmation 490 METHODS IN MEDICINE Rating of Exam. X-RAY EXAMINATION REPORT Page 3- No Exam. Name ¥■■■■■& . Case Plates Habitus ... " -- Notable findings: Date April. 19.* 1??9.... Exam. 1st. Fluor. 24 HOUR EXAMINATION - April 20th Two defecations; one at 18 hours and one at 20 hours after ingestion of Ba. Distribution: cecum (slight), ascending colon (slight), trans, colon, pelvic colon (slight). Great palpable mass occupying nearly entire upper half of abdomen, its general area corresponding to that of liver. Mass of strikingly irregular edge and surface. Tenderness, right central epigastrium, (1°); rather localized; not striking. 48 HOUR EXAMINATION - April 21st One good defecation 43-2 hours after ingestion of Ba. Colon empty. BARIUM ENEMA - April 22nd. Normal, rather prompt canalization by barium enema. Trans, colon below palpable mass seems fairly mobile; hardly adherent. X-Ray Diagnosis Clinical Diagnosis Operative Confirmation 491 THE HISTORY IN ORDER 492 METHODS IN MEDICINE BARNES HOSPITAL dental sheet Address _ Age «... X-Ray No „.«...««««--.. - Occupation Habits. Sex. Nativity - Chief Complaint „ « - - Condition on admission _... - " - Present illness Date and mode of onset _ _ - - Supposed cause, course, duration, treatment and results « .. _ - - - - - Chief symptoms .... -" - - - ... ._ -- - Medical Data. Condition of joints W z - - - -- - -j o Pallor Eyes... Sinuses z a z Nose Tonsils... Pharynx ...larynx m Bronchi... _ ..Lungs M Pleura Heart Pericardium Stomach Intestines Appendix - Nervous System ...Mental symptoms - - T P R Urine - - Blood: Hemoglobin % Red count White count Wassermann - - -•••- Bacteriological findings: Culture from Pathological findings ... - - Physical examination. Head and Neck .. Deformities Swelling Induration.... -• Fistulae Sinuses Pus... Enlarged glands - - ---- Evidence of injury-past or present .. -• - 11-20. IM. Form lit B Obverse side THE HISTORY IN ORDER 493 Mouth Deformity of jaws.. TongueGums Mucous membraneSaliva Remarks Teeth. General Condition.. Absentupperlower Impactions -upperlower Abscesses acutechronic FilledNeglectedDevitalized Canal fdling. Filled_PartialNone LoosenessDeposits- TartarCalculus.... Rotation---Pus BINDING LINE Inferior (Mark on teeth all anomalies, diseases or repairs.) Dental diagnosis Dental prognosis Results.. Reverse side 494 METHODS IN MEDICINE Form 116. 1M. 6-15. BARNES HOSPITAL DENTAL RECORD NameM. F. M. S. W. Register No Date191 Medical No Xray No A na e bae Bacteriology Histology C li nical D i agn o s i s DATE TREATMENT RESULT 495 THE HISTORY IN ORDER MNDI ; LINE BARNES HOSPITAL DENTAL RESEARCH RECORD Register No Medical No. Name Date Address X • Ray No. Age Occupation M. F. W. C. M. S. W D. Etiology J Before f Before Temperatures Blood Pressure's I After [ After Wasserman Test Urine Analysis Medical Diagnosis Teeth Filled, Canals Treated, Crowned, Neglected, Abscessed. Culture from Bacteriological Lab. Findings Pathological Lab. Findings Dental Diagnosis Dental Prognosis DATE TREATMENT - 1 1M * lb Form 116 496 METHODS IN MEDICINE BARNES HOSPITAL MEDICAL NO - Ad mitted Ward - BINDING LINE MONTH DAY OF DISEASE R p F* c 70 60 50 40 30 20 10 XT. 170 150 130 110 90 70 50 30 108 107 106 105 104 103 102 101 100 99 42 '41 -40 39 38 98 97 96 95 WT. 36 -35 Respirations Stools Total Fluid Intake Total Urine DOCTOR'S ORDERS Form 38-A 497 THE HISTORY IN ORDER SECTION OF HOSPITAL FORMS BEDSIDE NOTES BARNES HOSPITAL SERVICE NO N ame Date 19 w z J 0 z 0 z m Hours Temp Pulse Reap. Nourishment Medicines and Stimulants- Urine Stool REMARKS H Obver se s de 6-19. 10M. Form 62. METHODS IN MEDICINE 498 / Hour* Temp Pulse Reap. Nourishment Medicines and Stimulants- Urine Stool REMARKS □ z □ z G1 r Z m Revei ■se s ide THE HISTORY IN ORDER 499 BARNES HOSPITAL Register No. DIET LIST e Surgical No. NAME HOUSE HOUSE C CARE LIGHT SOFT SOLIDS LIQUIDS LIQUIDS s MILK 500 METHODS IN MEDICINE Form <& 5M ov BARNES HOSPITAL Register Nn. MEASUREMENTS OF URINE n„ . THE HISTORY IN ORDER 501 form 3» 5M op. BARNES HOSPITAL Register No MOVEMENTS „No DATE NAME D N 0 N □ N D N D N D N D N D N • 502 METHODS IN MEDICINE BARNES HOSPITAL NARCOTIC REPORT Ail derivatives and prepara- ~ OPIUM 1 lions containing any o these Doctors IN a me coca ne > CODEINE \ and must be recorded on this amount of Drug used. HEROIN ) ,I,"L WARD DAY DATE PATIENTS NAME PATIENT S ADDRESS DRUG DOSE NURSE This Rcpurt Must be Sent to the Supenniendent's Office Every Morning. ■ THE HISTORY IN ORDER 503 DEATH REPORT Name.Service. Address_ Admitted_Placed on Critical List I Yes' Ordered byFriends to be admitted to Wards ( No Notification(hour and method and name of person notified) Names and addresses of friends Removed from Critical ListDied Notification of Death, name, relationship, method, date and hour_ Friends came to Hospital Memoranda - Examined by 2M-3-18-Form 15 504 METHODS IN MEDICINE REFER BLANK FORM BARNES HOSPITAL Date 192 To the Service This patient whose record number is is referred to you from the Service. Our findings in the case are as follows: Please report to us as to . If the patient requires treatment in your service, please take charge of that aspect of the case. M. D. To the Service. Our findings in the case No. referred to us by you are as follows: We recommend the following treatment: Date192 M. D. All requests for consultations between members of the Medical and Surgical Staff, and also the opinion of the consultant, are to be made in writing, unless the consultation is held personally. Such written opinions are to be incorporated in the Hospital records. 4-20 2M Form 119 THE HISTORY IN ORDER 505 BARNES HOSPITAL X-RAY REQUISITION Hospital No.., Date Name Age F. M. W. C. M. S. W Address Diagnosis What desireo Free Pay Amt. Department M. p. 12-19 5M Form 121 WASSER MANN REQUEST Dite NameNo..Age (Last) (First) Service Specimen of Previous WassermannDateBy.... Present Diagnosis Venereal History Physical Signs of Syphilis Treatment a Result: Request of Report By 506 METHODS IN MEDICINE PRESCRIPTION BLANK BARNES HOSPITAL Ward Date M. D. Name 1018 5M Form 27 CLINICAL PATHOLOGY Name M. F Ward Date (second) (first) Age Clinic Diagnosis Clinical Data Material Wanted M.D. Result THE HISTORY IN ORDER 507 WASHINGTON UNIVERSITY MEDICAL SCHOOL Department of Hydro and Physical Therapeutics Barnes Hospital Date Please give M the following treatment: Diagnosis : How often Ward Room No Side Room No Private Pavilion No . Patient is in Will pay at the following rate: f Ward-Free or 50 cts. per treatment. < Side Room-$1.00 per treatment. I Private Pavilion-Regular rate. Dr 508 METHODS IN MEDICINE BARNES HOSPITAL Date Jun® 1, 194-21 I,-Wary fmith -, being related to J°bn Smithdeceased as Wife do hereby grant Barnes Hospital permission to hold a Post Mortem, on said body. Time of deliveryA*™. Signed...^ary £)r G.R. Herrmann . , . , i Nn 10-18-3M-Form 96 Should this be a coroners case? FORM 114. IM. 1*21. BARNES HOSPITAL Date Permission is hereby granted the department of Pathology to hold a Post Mortem Examination on the body of - - i Time of Delivery Superintendent 509 THE HISTORY IN ORDER Form 115 5M-4-17 C BARNES HOSPITAL TRANSFER NOTICE Date191 Nurse must send to office before making Transfer Nam e_N o. WardHas been seen by D r Please transfer to S ign ed Date OFFICE-Forward to Record Room M. D. 510 METHODS IN MEDICINE BARNES HOSPITAL CERTIFICATE OF RELEASE ST. LOUIS, TO WHOM IT MAY CONCERN: THIS IS TO CERTIFY THAT I HAVE BEEN FULLY INFORMED AS TO THE CONDITION OF Tn a m e ) ANDTHATI REQUEST DISCHARGE FROM THE BARNES HOSPITAL AND THAT I HEREBY RELIEVE THE BARNES HOSPITAL OF FURTHER RESPONSIBILITY IN THIS CASE. SIGNE D. RELATIVE OR FRIEND REMOVING PATIENT RELATION TO PATIENT vA/itnesses. WHEN THE DISCHARGE OF A PATIENT IS REQUESTED BY A RELATIVE, FRIEND OR THE PATIENT, AND THE ILLNESS IS SERIOUS. OR SUCH AS WILL DEMAND IM- MEDIATE FURTHER MEDICAL CARE. THE RESIDENT OR RESIDENT ASSISTANT PHY- SICIAN MUST FILL OUT THIS "CERTIFICATE OF RELEASE" AND HAVE IT SIGNED BY THE PERSON REQUESTING SUCH DISCHARGE, AND HE SHALL SIGN IT AS WITNESS. 7-1S-IM-Form 54. THE HISTORY IN ORDER 511 NOTE TO REFERRING PHYSICIAN Form 85-IM-op. BARNES HOSPITAL Datei191 Dr M referred to this hospital by you with a diagnosis of has been examined and has been found to have Remarks:....... INDEX A Acetone bodies, qualitative tests, 81 quantitative tests, 246 Acidosis, of diabetes, treatment, 393 Acids, antacid therapy, 429 diacetic, in blood, 246 in urine, 81 fatty, in feces, 73 hydrochloric, in gastric contents, 69, 70 lactic, in gastric contents, 71 uric, determination of, 226 {see blood chemistry methods) Actinic radiation treatment, 420 Adams-Stokes attacks, treatment, {see heart), 383 Adrenalin tests, 196, 197, 198 chart, 478 Albumin, differential reactions, 77 qualitative tests, 76, 77 quantitative tests, 78 Alcoholism, acute, treatment, 380 Alkaline solution for intravenous use, 370, 394 Alveolar air analysis, 209, 210 Amebiasis, treatment, 410 Amino-acid nitrogen determination, 231 Ammonium chloride therapy, 427 Anatomic outlines, 437, 447 Anemia, treatment of, 415 chart for history, 453 Anthelmintic therapy, 430 Apex-radial, pulse deficit, chart, 456 Apoplexy, management of, 391 Apparatus, in ward laboratories, 101 special, available for wards, 101 supplied each student, 101 Arnold's modified amido-acetophenon test, 81 Arsenic therapy, 422 Assistant resident physician's duties, 20 Atropin tests, 196, 197, 198 therapy, 426 Auricular fibrillation, chart, 456 treatment, 385 Autopsy permission form, 508 B Bacteriological and serological methods, 258, 260 Bass and Johns malaria concentration method, 186 Baths {see Hydrotherapy), 417 Bedside notes, history sheets, 497, 498 Bence-Jones body, tests for, 77 Benzidin tests, 72, 146 Bile tests, blood plasma, Blankenhorn, 138 Van den Bergh's, 140 urine, foam and nitric acid, 82 Bilirubin, blood plasma estimation, 138, 140 duodenal contents, 131, 132 feces, 73 urine, 82 Bismuth therapy, 428 Blankenhorn's tests for bile in plasma, 138 Bleeding time, (Duke), 179 Blood, benzidin tests, 72, 146 carbonates, 212 carbonates, plasma, whole blood (Van Slyke), 212 characteristic cell types, 88 charts, special, 453 chemistry methods, 212 acetone bodies (Van Slyke-Fitz), 246 amino-acid nitrogen (Folin), 231 calcium (Clark), 253 chlorides (McLean, etc.), 251 chlorides (Whitehorn), 232 cholesterol and fatty acids (Bloor, etc.), 241 cholesterol (Myers-Wardell), 244 creatinine and creatine (Folin- Wu), 225 disturbances, diagnostic criteria, 180 513 514 INDEX Blood chemistry methods-Cont'd nonprotein nitrogen (Folin-Wu), 221 oxygen (Van Slyke), 216 protein precipitation of, 220 sugar (Folin), 234 sugar (Lewis-Benedict), 239 sugar (Myers-Bailey), 238 sugar (Shaffer-Hartman), 235 system of Folin-Wu, 220 urea, urease, autoclave (Folin), 225 uric acid (Folin), 226 values for normals, 257 cultures, 267 fragility of erythrocytes, 180 grouping and matching, 176 guaiac tests for, 72 malaria plasmodia concentration, 186 oxidase staining of leucocytes, 184 oxygen determination, 216 platelet counting, 179 pressure chart, 455 routine morphological examinations, 83 routine study of blood disease cases, 109 spectroscopic test, 73, 146 technic, for blood grouping, 176 for counting erythrocytes, 84 for counting leucocytes, 86 for counting platelets, 179 for estimating hemoglobin, 87 for making blood films, 88 of estimating coagulation time, 178 of estimating bleeding time, 179 of vital staining, 182 Blood-urine record for history, 440 449 Boas' reagent and test, 69 test meal gruel, 112 Body fluids (see transudates and ex- udates), 94 classification of pathologic types, 96 cultures, 265 methods of examination, 96 paracentesis technic of abdominal, 95 puncture, technic of pericardial, 95 thoracentesis, technic of, 94 Botulinus antitoxin administration, 431 Bran bread preparation, 336 Bromide therapy, 426 c Calcium determination in blood (Clark), 253 in foodstuffs, 322 Calomel therapy, 428 Carbohydrate tables, 337 Carbon dioxide content of alveolar air (Marriott's method of analy- sis), 210 Carbon monoxide poisoning treatment, 373 Carbolic acid poisoning treatment, 277 Carbonate determination in plasma and whole blood (Van Slyke, Cul- len, Stadie), 212 Cardiac cases routine study, 109 chart for history, 461, 463 decompensation (see heart), 381 Cardio-renal chart for history, 469 Case studies routine for, all patients, 107 blood diseases, 109 cardiacs, 109 diabetics, 108 endocrines, 109 gastrointestinal, 109 hemopoietic, 109 hypertension, 109 nephritic, 109 pneumonia, 107 pulmonary, 107 typhoid fever, 108 Catarrhal jaundice treatment, 404 Cerebral hemorrhage, management, 391 Cerebrospinal fluid (see spinal fluid), 92 chart, 481, 483 Certificate of release form, 47, 510 Charts, standard, adrenalin test, 479 anemia, 453 apex-radial, 456 basal metabolism, 480 blood pressure, 455 blood special, 453, 454 cardiac, 461, 463 cardio-renal, 469 cerebrospinal fluid, 481, 483 diabetic data, 474, 476 duodenal, 467 electrocardiographic 458, 460 fluid intake-output, 457 gastric analysis, 464, 466 leukemia, 454 metabolism, 471, 473 perimeter, 484 INDEX 515 Charts-Cont'd pulse, respiration, and tempera- ture, 496 sugar tolerance test, 477, 478 twelve hourly renal test, 470 two hourly renal test, 471, 473 vestibular test, 485 vital capacity, 457 weight, 457 Chemistry methods, physiological (see blood), 209 Chloral therapy, 426 Chloride determination in blood and body fluids (McLean), 251 Whitehorn, 232 Chlorides in spinal fluid, 93 Cholesterol and fatty acids determina- tion in blood (Bloor), 241 Myers-War dell, 244 Cholesterol and lipoids in foodstuffs, 319 Clinical pathology form, 506 Coagulation time of blood (Minot and Lee), 178 Cocaine poisoning, acute, treatment, 378 Coleman-Shaffer diets, 284 Colon-typhoid differentiation, 264 Coma of diabetes, treatment, 393 Complement-fixation test technic, 271 Concentration diuresis test (Olmsted), 165 Constipation treatment, 408, 313, 314 Consultation request form, 504 Creatinine and creatine determination, 225 Cultures, bacteriological technic, 260 D Death report form, 503 Defecation record, 501 Deficit in apex-radial rate chart, 456 Dental sheets, 492, 495 Desensitization to horse serum, 430 Diabetes mellitus, acidosis and coma, 393 chart, 476 data 474 dietetic treatment, 335, 394 insulin treatment, 352, 393 Diacetic acid tests, 81 Diarrhea, treatment, 311, 409 Dietetic treatment of arthritis, 294 of blood diseases, 320 of calcium disturbances, 322 of constipation, 312, 313 Dietetic treatment-Cont'd of diabetes mellitus, 335 of diarrhea, 311 of edema, 324 of gall-bladder disease, 319 of gastric ulcer, 300 to 308 of gout, 317 of nephritis, 327 of obesity, 296 of tuberculosis, 282 of typhoid fever, 283 to 296 .Diets, 277 a practical nephritic (O'Hare and Wickers), 332 arthritis (Pemberton), 294 axioms for the diabetic, 339 bland, 311 bran bread, 336 calcium content, 322 carbohydrate content, 339 cholesterin and lipoid content, 349 coarse, laxative, 312 Coleman-Shaffer, 284 constipation, atonic, 314 spastic, 313 convalescent tuberculosis, 282 Epstein, 325 high caloric, 283 to 291 high fat, 350 high nephritic, 327 intestinal (Schmidt's), 315 iron content, 320 Karell, 325 laxative, 312 light, 277 liquid, 279 list charts, 499 Lenhartz's ulcer, 300 modified, 302 low caloric, 296 low carbohydrate, low fat, 336 low nephritic, 329 low protein, high caloric, 330 maintenance, 346 medium high caloric, 281 medium nephritic, 328 method of increasing, 346 Mills' ulcer, 308 Mosenthal's renal test, 160 nonlaxative, 311 obesity, 296 observation, 335 practical nephritic, for O. P. D., 332 protein content, 344 recipes for high caloric, 291 recipes for practical nephritic, 333 reduction, 296 516 INDEX Diets-Cont'd regular, 279 Schmidt's, 314 Schmidt-Strasburger, 142 Sippy ulcer, 304 modified, 305 soft, 278 starvation, 336 typhoid, 283 Digitalis, administration, 385, 387, 424 cat method of standardization, 192 Diphtheria, antitoxin administration, 431 toxin-antitoxin administration, 431 toxin test (Stock), 207 Dock's, test breakfast, 111 twenty drugs, 423 Drugs, acting promptly and power- fully, 396 Dock's twenty, 423 acid and antacid, 429 ammonium chloride, 427 anthelmintics, 430 arsenic, 422 atropin, 426 bismuth, 428 bromides, 426 calomel, 428 chloral, 426 digitalis, 424 iodids, 423 ipecac, 429 iron, 423 morphine, 422 nitrites, 429 opium, 422 opotherapy, 430 phenacetin, 427 quinine, 429 salicylates, 425 sera, 430 strychnin, 423 vaccines, 431 narcotic rules, 368 Duodenal contents, analysis, 116, 117 chart, 467 fractional examination, 117 gall-bladder diagnostic, 126 methods of aspiration, 116 pancreatic enzymes, 117 Einhorn's tubes, 118 McClure's methods, 119 pigment estimation, 131 Schneider's method, 131 Duties, assistant resident physician, 20 Duties-Cont'd internes, 26 resident physician, 17 senior students, 55 E Edema, dietetic treatment, 329 diuretic treatment, 383 Ehrlich's, aldehyde test for urobilin- ogen, 82 Einhorn's tubes for pancreatic func- tion, 118 Elastic tissue, concentration of, 68 Electric light baking, local, 417 Electrocardiographic record sheets, 461 Electrodes for electrocardiography, 191 Endocrine cases, routine study, 109 Enemata, prescriptions for, 411 Entameba cysts in stools, 149 Enzymes, gastric, 115 pancreatic, 117 Equipment for ward workers, 100 of ward laboratories, 101 Equivalents, table English-metric, 359 Ewald's test breakfast, 112 Exercise, graduated or passive, 419 tolerance tests for cardiacs, 189 Exudates (see body fluids), 96 F Fat, indigestion, 144 stains, 73 Feces, bile in, 73 blood in, 72 chemical examination, 72, 73 macroscopic, 72, 73 microscopic, 73, 74 cultures, 263 entameba cysts, 149 fats in, 73, 144 fatty acids in, 73, 144 food particles in, 73 functional tests, 142 Schmidt-Strasburger diet, 142 hydrobilirubin in, 73, 150 Schmidt's HgCl2 test, 73 mercury, tests for, in, 151 methods of study, 72 occult blood tests, 72, 146, 147 guaiac and benzidin, 72, 146 spectroscopic, 73, 147 ova concentration, 148 soaps, 73, 144 stains, carbol fuchsin, Lugol's and Sudan III, 73 INDEX 517 Ferments, gastric, 115 pancreatic, 117 Fibrinolysin test, 141 Fluid intake and output chart, 457 Fragility test for erythrocytes, 180 Front page, of composite history, 435 Functional tests, cardiac, 189 gastric, 111 intestinal, 142 renal, 157 G Gastric analysis, aspiration procedures, 112 charts, 464, 466 chemical tests, 69, 70, 71 ferments, 115 fractional, Rehfuss, Gorham, 113 function tests, 111 record sheets, 450, 451 retention test, 111 string test, 114 test meals, 112 ulcer treatment general, emergency, 408 Gastrointestinal diseases, diet, 300 orthodiagram, 491 routine study of, 109 special procedures for, 111 Gerhardt's modified ferric chloride test, 81 Globulin, tests for excess, in spinal fluid, 92 Glucose, differentiation of false re- action, 79 qualitative estimation in urine, 79 quantitative estimation in urine, 80 and in the blood (see blood chem- istry), 234 spinal fluid, concentration of, 93 solutions for intravenous use, 371 tolerance test, 195 chart, 477, 478 Goodpasture's peroxidase stain for leucocytes, 185 Gout, treatment of, 317 Graham's oxidase stain for leucocytes, 184 Gram's stain, 68 Green history sheet, sputum, stomach, stool record, 450 Grouping of blood for transfusion, 176 Guaiac test, 72 Gum acacia glucose solution, prepara- tion of, 371 Gunning's modified iodoform test for acetone, 81 Gunzburg's reagent and test, 69 H Habitus tvpes, anatomic outlines, 437, 438 Heart, block attacks, (Adams-Stokes), treatment, 383 disease cases, routine study, 109 disease management, 384 failure, acute treatment, 381 station charts, 461, 463 Heat stroke treatment, 394 Hemoglobin estimation Palmers (CO method), 174 Sahli, Tallqvist, 87 Hemoglobinometer standardization, 168 Jacobson, 169 Terrill's, 171 Van Slykes', 169 Hemophilia, diagnostic criteria, 180 Hemopoietic diseases, routine study, 109 Hemorrhage into brain, management, 391 Hemosiderin in cells in urine sediment, 167 History, abbreviated, 63 abstracts, 61, 64 composite order of sheets, 432 diagnoses, 60, 62 margin stamps, 436 notes and suggestions, 58 sheets, regular form, 436 special cases, 64 Horse serum, desensitization, 431 Hydrobilirubin, tests for, 73, 150- Hydrotherapy, 417 actinic radiation, 420 baking, local, 417 electric light, 417 exercise, 419 massage, 419 Nauheim baths (artificial), 419~ requisition form, 507 Scotch douche, 418 whirlpool baths, 419 Hyertension cases, routine manage- ment, 392 routine study, 109 I Immunological studies, 205 Infectious diseases, general manage- ment, 398 isolation rules, 398 518 INDEX Infectious diseases-Cont'd regulations for, 399 Insulin, the use of, 352 Intake and output of fluid, chart, 457 Interne's duties, 26 Intracutaneous pneumotoxin test, 207 Intravenous therapeutic solution, prep- aration of, 370 alkali, sodium bicarbonate (4%), 370, 394 anticoagulant, sodium citrate, 371 glucose 50% stock 5% emer- gency, 371 hypertonic gum acacia glucose, 371 normal physiologic saline (0.85%), 370 sodium bicarbonate (4%), 370, 394 sodium citrate, 371 Iodide therapy, 423 Ipecac therapy, 429 Iron in foodstuffs, 320 therapy, 423 J Jacobson's rufigallic acid hemoglobin standard, 169 Jaundice, catarrhal, treatment by duo- denal lavage, 404 differentiating types by plasma bile content, 138 K Kelling's test for lactic acid, 71 Kidney function test, 157 disease, treatment, 390 L Laboratory, methods and routines (see special headings as sputum, stomach contents, etc.), 67 rules, 66 specimens to be preserved, 96 ward routine for specimens, 96 Lange's modified nitroprusside test, 81 Lenhartz's ulcer diets, 300 Leukemia, chart for history, 454 treatment, 416 Liver function tests, 134 Lumbar puncture technic, 90 Lyons-Meltzer gall-bladder and biliary tract diagnostic procedure, 126 M Malaria concentration method (Bass & Johns), 186 treatment, 404 Margin stamps for history sheets, 436 Marriott's method of analysis of alveolar air, 209 Massage and exercise, 419 McClure's method for estimating pan- creatic functions, 118 Media for growing bacteria, 267 for preserving stock cultures, 268 Meltzer-Lyons biliary tract diagnostic procedure, 126 Meningococcus antitoxin administra- tion, 431 Mercury bichloride poisoning treat- ment, 374 in excreta, tests for, 151 Vogel and Lee method, 151 Willard and Elliott method, 154 quartz radiation, 420 Metabolism, basal chart, 480 general charts, 471, 473 Methyl alcohol, detection in excreta, 155 poisoning treatment, 377 Mills' anatomic habitus outlines, 437, 438 ulcer diet, 308 Morphine poisoning acute, treatment, 379 therapy, 422 Mosenthal's renal test and diets, 160 Murphy drip, 414 N Narcotic drug rules, 368 report sheet, 503 Nauheim baths, 416 Nephritis, cardio-renal, charts for, 468 dietetic treatment, 327 routine management, 390 routine case study, 109 Nitrite therapy, 429 Normal salt solution, preparation, 370 values in blood chemistry, 257 Nonprotein nitrogen determination, 221 Note to referring physician, form, 511 O Obesity dietetic treatment, 296 Oedema dietetic treatment, 329 diuretic treatment, 386 Olmsted-Day concentration diuresis test, 165 INDEX 519 Opium therapy, 422 Opotherapy, 430 Organisms, concentration in sputum, 68 differentiating in sputum, 68 Ova in stools, concentration, 148 Oxidase and peroxidase reactions, 184 Oxygen determination in blood, 216 P Palmer's carbon monoxide hemoglobin method, 174 Paracentesis technic, abdominal, 95 pericardial, 95 pleural (thoracentesis), 94 Parasites, intestinal, treatment, 409 Peptic ulcer treatment, general dietetic, 300 hemorrhage, perforation, pyloric ob- struction, 408 Perimeter charts, 484 Pharmacologic tests, 196 adrenalin, atropin, pilocarpin, 197 Pharmacodynamic reactions, 198 adrenalin, atropin, pilocarpin, 198 Phenacetin therapy, 427 Phenol poisoning treatment, 377 Phenoltetrachlorphthalein tests for liver function, 134, 136 Phenolsulphonephthalein test for kid- ney function, 157 Physical examination, 60 Physiological chemistry methods, 209 saline solution preparation, 370 Pilocarpin tests, 196, 197, 198 Pink history sheet, blood and urine, 448, 449 Pituitrin test, 204 Plasma, bile content in differentiating types of jaundice, 138 fibrinolysin content, 141 retention of phenoltetrachlorphtha- lein, 136 Platelet counting in blood (Otten - berg), 179 Pneumococcus antitoxin administration, 431 typing, 261 Pneumonia cases, general treatment, 401 routine study, 107 Pneumotoxin test, 207 Poisoning, treatment of, 372 alcohol (acute), 380 carbon monoxide, 373 cocaine (acute), 378 mercury bichloride, 374 Poisoning-Cont 'd methyl alcohol, 377 morphine (acute), 379 phenol, 377 strychnin, 379 wood alcohol, 377 Prescription blank form, 506 Procedures to be undertaken in the more common types of cases (see case studies), 107 Protein sensitization tests, 208, 430 Pulmonary diseases, routine study, 107 edema, acute, treatment, 383 Pulse deficit chart for history, 456 Purpura, diagnostic criteria, 180 Pus cultures (see body fluids, exu- dates), 265 Q Quinidin therapy, 387 Quinine therapy, 424 R Record room rules, 42 Rectal taps, 413 Refer blank, consultation request, 504 Referring physician, note to, 511 Release certificate, 510 Renal, disease treatment, 390 function tests, 157 Resident physician's duties, 17 Riegel's test dinner, 112 Robinson's method for detecting methyl alcohol in excreta, 155 Rules, laboratory, 66 record room, 42 superintendent's, 53 x-ray department's, 49 S Salicylate therapy, 425 Schick test, 206 Schlesinger's zinc test for urobilin, 82 Schmidt's mercury bichloride test, 73 Schmidt-Strasburger diet, 142 Scotch douche, 418 Senior student's duties, 55 Serological routine methods, 258 Serum, antibotulinicum, 431 antidiphthericum, 431 antidiphtheria toxin-antitoxin, 431 antimeningococcicum, 431 antipneumococcicum (Type I), 431 desensitization, 431 Shock treatment, 396 520 INDEX T Taeniasis treatment, 409 Temperature, pulse and respiration chart, 496 Terrill's powdered acid hematin stand- ard, 171 Test meals, Boas', 112 Dock's, 111 Ewald's, 112 Kussmaul's, 112 Mosenthal's, 160 regular dinner, 112 Riegel's, 112 Schmidt-Strasburger, 142 Tetanus antitoxin administration, 431 Therapeutic methods, 365 rules, 365 sheet, 368 solutions, pro injection, 370 Thoracentesis technic, 94 Thrice cooked vegetables, preparation of, 337 Throat cultures, 262 Thyroid test, 201 Thyroxin test, 204 Tolerance tests, exercise for cardiacs, 189 sugar for endocrines, 195 sugar charts, 477, 478 Topfer's reagent and method, 70 Transfer notice blank, 46, 509 Transudates (see body fluids), 96 Tray contents, neurological, 105 regular examination, 104 vaginal and rectal, 105 Treatment (see under condition to be treated) Tubercle bacilli culturing, 262 in sputum, 68 Tuberculin test, 205 Twelve hour urinary chart, 468 Two hourly renal test, 160, Chart, 470 Typhoid fever, routine study, 108 treatment, 283, 401 vaccine, technic, 431 Ufifelmann's test for lactic acid, 71 Ulcer diets, 300 to 311 treatment including complications, 408 Uncinariasis treatment, 411 Urea determination methods (Folin), 225 Urea, spinal fluid content of, 93 Uremia, acute, treatment of, 389 Uric acid determination method (Folin), 226 Sippy diets, 304 Smallpox, virus vaccinicum technic, 431 Sodium bicarbonate intravenous solu- tion, preparation of, 370, 394 Sodium citrate solution, preparation of, 371 Specimens, laboratory ward routine, 96 to be preserved, 96 Spectroscopic test for blood, 73, 147 Spinal fluid, bacteriological examina- tion, 93, 266 cell counting methods, 92 chart, 481, 483 chloride excess determination, 93 cultures, 266 globulin excess determination, 92 glucose excess determination, 93 lumbar puncture technic, 90 technic of lumbar puncture, 90 urea excess determination, 93 Spirochetae pallidae, cover-glass method, 271 Sputum, cultures, 261, 262 examination routine, 67 methods of study, 67 stomach, stool record sheet, 450, 451 Stains, carbol fuchsin for fatty acids and soaps, 73 Gram's, 68 oxidase and peroxidase (Graham, Goodpasture), 185 Sudan III, 73 vital for erythrocytes, 182 Ziehl-Neelsen, 68 Standardization of hemoglobinometers, 168 Stomach contents (see gastric) exam- ination routine, 69 methods of study, 69 record sheet of history, 450, 451 Stool cultures, 263 examination routine (see feces), 72 record sheet of history, 450, 451 Strauss method for lactic acid, 71 Strychnine, poisoning treatment of, 379 therapy, 423 Sugar tolerance test, 195 chart, 477, 478 determination in blood (see blood chemistry), 234 Superintendent's rules, 53 autopsy order form, 508 Sympathicotonia, symptoms, 200 INDEX 521 Urine, acetone tests in, 81 albumin test in, 76 Bence-Jones body tests in, 77 cultures, 265 diacetic acid tests, 81 glucose tests in, 79 measurement chart, 500 mucin and nucleo-albumin, tests in, 177 pigment, tests in, 82 quantitative albumin methods, 78 Esbach's, Kwilecki's, Tsuchiya's, 78 quantitative glucose methods, 80 Benedict's, 80 twelve hourly chart, 468 Urobilinogen and urobilin, 149 duodenal content estimation, 133, 149 Ehrlich's aldehyde test, 82 Schlesinger's zinc test, 82 stool content, 73, 150 urine content, 82, 151 Wilbur and Addis methods, 149 V Vaccines, autogenous, 431 vaccinia staphylococcicum, 431 streptococcicum, 431 typhosum, 431 virus vaccinicum, 431 Vagotonia symptoms, 200 Van den Bergh's method for bile con- tent of plasma, 140 Van Slyke's methods (see blood chem- istry) Vaughn's benzidin method, 146 Vegetables, carbohydrate content tables, 340 thrice cooked preparation, 337 Vegetative nervous system status de- tails, 199 Vestibular test chart, 485, 486 Vital capacity chart, 457 staining for erythrocytes, 182 Vogel and Lee method for detecting mercury in excreta, 151 W Wassermann technic, 271 request form, 505 Weight chart for history, 457 Whirlpool bath, 418 Wilbur and Addis methods for uro- bilin and urobilinogen, 149 Willard and Elliott method for detect- ing mercury in excreta, 154 Wohlgemuth's benzidin ortizin method for detecting blood, 146 Wood alcohol detection in excreta, 153 poisoning treatment of, 377 X X-ray department rules, 49 examination report, 487, 490 preparation of patients, 50, 51 requisition form, 505