He eer (OLN it cuit oi ike xh ey ON, i i PICS Mea) ik a SLaty Wi Maitre Tide TSA May hance Oh anny a iy i ite fue Can , nie i a) i i He i i thy hy Oe 4 > i #4) ie i b ty i Gin eae HN Psat aM i i iN ath Aid oe aa Asrteytot ut i by At Denne ens ee can tae maieane re p ms LY Naas I cM i oe i Phe) Cen) nt pi i Gy Voie sareh tae aah eenat URIUUn Ur ue eng ec aee uly iy By Be ea A oun CCN ita Teh SD Ratt RNa SUAS WSCA NOE SU ten saat C CLAY vy AAA Ars APL iO CAAK MON a ot aoe ¥ > oe HAM BS HS OM Kanaan ete Baa Cane ae Ne TAs % es Rest ‘ ', ODOM ens HRCA Sn pl vari teleley Peete PTY Ain AMAAKE MAA AY ey ienEe fenite BG MaaaKe cai Dna A any eS Ce ae 4 ‘ at AOR aC OE CEM AMAA AE GSS Ra Wire OnOAD AGRA A CA ATG POE Bataan estat enna sean Ser tok (oc tO ae a) eas Oe a (4: ae al any Be oh Ne (AA an i HY ne (As Ke re BKK pacino ga) iad HAL Sei ASN ee ie MA On yi on i fe tae y HA fase f C Add r MUA AG it { Zz RE i p45 CORNELL UNIVERSITY. THE Roswell P. Flower Library THE GIFT OF ROSWELL P. FLOWER FOR THE USE OF THE N. Y. STATE VETERINARY COLLEGE 1897 2757 ie ae aN 7 / => fea e Lie [ee wee a sens UNIVERSITY LIBRARY A GUIDE TO THE CLINICAL EXAMINATION THE BLOOD FOR DIAGNOSTIC PURPOSES BY RICHARD C. CABOT, M.D. WITH COLORED PLATES AND ENGRAVINGS Fourth Revised Ldition NEW YORK WILLIAM WOOD AND COMPANY MDCCCCI: T "own, 4 2/5 # = ae ce Noi 2250 CopyRicHt, 1901, By WILLIAM WOOD AND COMPANY. KB 145 ar /70/ TO WILLIAM SIDNEY THAYER, M.D., ASSOCIATE PROFESSOR OF MEDICINE IN JOHNS HOPKINS UNIVERSITY, IN GRATEFUL RECOGNITION OF THE STANDARD OF THOROUGH WORK ESTABLISHED BY HIM. PREFACE TO THE FOURTH EDITION. Tuts book becomes with each succeeding edition more indebted to the labors of the internes of the Massachusetts General Hospital and less my book. Of the twelve thousand observations on which it is now based, less than three thousand represent my own work. The remainder I owe to the generosity of the visiting physicians of the hospital and to the zeal and skill of their internes. As the de- tails of the technique employed have been substantially the same throughout the whole body of data, they form a single group su- perior in bulk and in detail to any elsewhere recorded. Our twenty- eight hundred observations in one thousand cases of typhoid fever are an example of the wealth of statistical data on which the con- clusions of the book are based. The text has been almost entirely rewritten. The section on serum diagnosis has been abridged and the table of contents abbre- viated so that in spite of so many pages of new matter the book is not greatly increased in size. The most extensive changes are in the sections on pernicious anemia, leukemia, typhoid fever, and the diseases due to animal parasites. JI have profited largely from the magnificent work of A. E. Taylor on leukemia, the extensive observations on typhoid analyzed by Thayer, and Ewing’s studies in malarial parasitology. 190 MarLuoroucH STREET, Boston. August, 1901. TABLE OF CONTENTS. BOOK I. Introduction. ScoPE AND VALUE OF BLOOD EXAMINATION, . ‘ ‘ PART I. Meruops oF CLINICAL EXAMINATION OF THE BLOOD. CHAPTER I. I. Estimation of the Total Volume or Mass of Blood, 3 7 : II. Examination of the Fresh Blood, : ‘ . rl ‘ CHAPTER II. I. CountTIne THE CoRPUSCLES (Thoma-Zeiss Instruments), Counting the Red Corpuscles, Counting the White Corpuscles, . Counting both Red and White Corpuscles with the Same Pipette, II. Durham’s Modified Hemocytometer, A ‘ A CHAPTER III. OrHEeR Metuops oF EXAMINATION, . ‘ 7 . . fs Oliver’s Hemocytometer, . : e : le . : ;. The Hematocrit, . . 3 ‘ - 5 7 . é i Heemoglobin Estimation, . ‘ . ‘ 2 . . . I. Tallqvist’s Hemometer, . zi z . " 7 . II. Dare’s Hemoglobinometer, . i e 2 ‘ ‘: : III. Oliver’s Hemoglobinometer, ‘ : : a . . IV. v. Fleischl’s Hemometer, . : 3 : 5 . PAGE 12 13 19 20 23 Q7 27 32 32 33 35 3% vili TABLE OF CONTENTS. Estimating the Specific Gravity, é : . Study of the Finer Structures of the Blood Bacteriological Examination, Other Methods of Examination, PART II. PuysioLocy oF THE Buoop. CHAPTER IV. APPEARANCE OF FrEsH Norma Buoop, I. Red Corpuscles, II. White Cells, III. Blood Plates, IV. Fibrin Network, ; Average Diameter of Red Cells, 7 Normal Number of the Red Cells, Influence of Menstruation, Parturition, Tadtation, Influence of Vasomotor Changes, Influence of Nutrition, Influence of the Seasons, Influence of Fatigue, 3 ‘ ‘ 3 Influence of Age, , ‘ : Normal Number of White Cells. . Normal Number of Blood Plates, Miiller’s “Blood Dust,” CHAPTER V. FINER STRUCTURE OF THE BLOOD, 3 Appearances of Dried and Stained Specimens, . Red Cells, White Corpuscles, Lymphocytes, Transitional Cells, Polymorphonuclear Neutrophites, Eosinophiles, Basophiles, Terminology, ‘ - Normal Percentage of Each Variety, : Myelocytes. . s ¢ Eosinophilic Myelocytes, Degenerated Leucocytes, Transitional Neutrophiles, Tirck’s “Stimulation Forms,” PAGE 39 41 47 49 15 51 53 53 54 55 56 57 57 57 58 58 58 59 59 60 61 61 61 62 62 63 64 65 66 66 67 68 70 70 71 71 TABLE OF CONTENTS. ix PART III. GENERAL PATHOLOGY OF THE BLoop. CHAPTER VI. PAGE UneEQuat DIisTRIBUTION OF THE BLooD—PoLycyTH&MIA—DILUTION AND CONCENTRATION OF THE BLOOD, . F ; é ‘ . 72 1. Unequal Distribution, . : ‘ 5 ‘ ‘ . 7 2. Local or Peripheral Polycythemia, - : 3 : . 7 (a) General Cyanosis, ; 2 4 3 ‘ ‘i i . 7 (6) Local Cyanosis, ‘ - 2 Z a - * . 13 8. Temporary Serous Plethora, . ; 5 . 3 ; 3 . 4 Polycythemia, B : . ‘ : ‘ . 14 Concentration of the Blood, : 3 . . ‘ F ; . 15 The Blood in High Altitudes, ‘ , : < ; . . 8 Phosphorus and CO Poisoning, . F : - ‘ . . 9 CHAPTER VII. ANMIA AND HyDR2MIA, . : ‘ , 3 ‘ 3 ‘ . . 80 Anemia, 3 , . : ; . a . . . 80 Pallor and Ansmia, A ; s 2 5 ‘ : i . 80 “Tropical Anemia,” . - . Sl Distinction between Danaey and Secondary Ania, . . 81 Secondary Anemia, . ‘ : . 83 I. First Stage—Loss of Color. Weight; ‘andl Size, ‘ : . 838 II. Second Stage—Poikilocytosis and Degeneration, . 3 . 88 (a) Endoglobular Changes, . s ‘ ‘4 F : . 84 (0) Crenation and Poikilocytosis, . ; 7 . : . 84 (c) Motility, . f A ‘ ‘ : ° i 6 . 84 (d) Oval Shape, .. ; ‘ c . 7 . 85 (e) Changes in Staining Properties, - : 3 . 85 (f) Lessened Diameter, r A . - ‘ i . 86 (g) Loss of Hemoglobin, : . : a . ‘ . 86 III. Third Stage—Deglobularization, . . . . . . 87 IV. Nucleated Red Corpuscles, . ‘ F ‘ ‘ ‘ . 87 (a) Normoblasts, . ‘ 3 3 s $ ‘ c . 87 (0) Megaloblasts, . : : : . . 3 7 . 88 (c) Microblasts, ‘ 7 P - F : é ‘ . 90 (d@) Atypical Forms, 3 : . - A 7 . 90 Summary, . : ‘ : : : , 6 . 91 Hydremia, ; : : ‘ 5 . . . . . - 98 x TABLE OF CONTENTS. CHAPTER VIIL PAGE Lrvcocytosis—LyMpPHocyTosis—EOSINOPHILIA—MYELOCYTES, 2 . 94 Definition of Leucocytosis, . : ; : 2 % . 7 . 94 Physiological Leucocytoses, ‘ 6 ; . ‘i 3 ‘ . Digestion Leucocytosis, en Diagnostic Value,. . by Gab cen wh ah cat oi 208 Leucocytosis of the New- Barn, : : : ‘ A é . 99 Leucocytosis of Pregnancy, . - F ji ; : 7 - 100 Leucocytosis after Parturition, . - .» 100 Leucocytosis from Exercise, Massage, and Cold Baths, : . 100. Terminal Leucocytosis, ‘ : . : : ‘ ‘ . 103 Pathological Leucocytoses, io Re ae OE Post-hemorrhagic Leucocytosis, . : F ; . $ . 104 Inflammatory Leucocytosis, . : ‘ , é 7 . 104 Toxic Leucocytosis, . ‘ ‘ , A 3 . 107 Leucocytosis of Malignant Disease, ‘ . 108 Leucocy tosis due to Therapeutic and Experimental Influences, . 109 Cell Structure of the Leucocytes in Leucocytosis, : F . 110 Absence of Leucocytosis, . ‘ é : ‘ F . $ . 111 Leucopenia, 3 2 ‘ ‘ ; i‘ 3 : z é . 112 Lymphocytosis, . ; ; : ‘: ‘ - . ; . . 113 Diagnostic Value, . i i 5 ‘ i 3 ‘ 5 . 115 Eosinophilia, ‘ 3 : ‘ ‘ 7 e . 115 Diminution in Kosinophiles, : . fs . . . . 117 Diagnostic and Prognostic Value, A ey 3s A 7 . 118 Myelocytes, ‘ 4 ‘ ; . % ‘ . A . 118 CHAPTER IX. GENERAL PATHOLOGY OF THE BLOOD AS REGARDS H&MOGLOBIN, FI- BRIN, LIP#MIA, MELANZMIA, AND HEMORRHAGE, . ‘ . 120: Hemoglobin and the “Color Index,” . , ‘ x ‘ . . 120 Fibrin, . : ‘ ‘ ‘ ‘ 5 é ‘i ‘ : 3 . 121 Lipemia, . 3 ‘ 2 . J 7 3 : %, . 122 Melanemia, . 4 F : i ‘ ; ‘ 3 ; : « 122 Hemorrhage, : : 7 . 123. Changes in the Blood Resulting from Hemorthage 5 5 . 123 Blood Regeneration, . . s é - 123 Regeneration of Red Cells, . ; ‘ ght ag . . 124 Blood Crisis, . : : 5 - 5 3 . 124 Regeneration of White Cells, i ’ . 125 Importance for Surgery of Blood Counting after Hemorrhage, . 126 Chronic Hemorrhage, . : : . . 7 . ‘ : . 127 TABLE OF CONTENTS. BOOK II. Special Pathology of the Blood. PART I. DIsEASES OF THE Buioop. CHAPTER I. THe Primary AN2MIAS, 1. The Blood in Pernicious Avesants, 7 1. Volume and Oxygen Capacity, 2. Gross Appearances, és Red Cells and Hemoglobin, Quantitative Changes, White Cells, Quantitative Changes, Hemoglobin, Qualitative Chan gee, 1. Red Corpuscles, : (a) Increase in Diameter, (6) Deformities in Shape, (ce) Staining Properties, 2. Nucleated Red Corpuscles, 8. White Corpuscles, The Blood in Remissions, 3 Characteristics of Pernicious Avorn, Summisry; Diagnostic Value of Pernicious Anemia, 1. Pernicious Anemia and Chlorosis, 2. Pernicious Anzemia and Malignant Disease, 3. Pernicious Anemia and other Secondary Anemias, . 4, Pernicious Anemia and Leukemia, . ‘ Prognostic Value of the Blood in Pernicious Anzemia, 2. Fatal Anemia with Hypoplastic Marrow, 3. The Blood in Chlorosis, ‘ The Blood in Gross, é Red Cells and Hemoglobin, Quantitative Changes, Qualitative Changes, Specific Gravity, White Cells, Quantitative Changes, Qualitative Changes, Blood Regeneration in Chlorosis, ; Chlorosis without Known Blood Changes, Summary and Diagnostic Value, xi PAGE . 131 131-151 . 131 . 181 . 182 . 132 . 135 . 135 . 136 . 137 . 187 . 137 . 187 . 139 . 139 . 142 . 144 . 146 . 146 . 146 . 147 . 148 . 149 . 149 . 152 . 153 . 153 . 154 . 154 . 156 . 157 . 157 . 157 . 158 . 158 . 158 . 159 xii TABLE OF CONTENTS. CHAPTER II. Lrvxamia, i S fe eS . I. Myeloid Leukemia, 3 . : . ; Red Cells, 5 7 Quantitative Changes, i . . . . Qualitative Changes, ‘ : . White Cells, . : , : : ; > Quantitative Changes, ‘ . é . . Qualitative Changes, 1. Myelocytes, . . 2. Polymorphonuclear Cells, j . 3. Lymphocytes, 4. Eosinophiles, 5. Basophiles, 6. Mitoses, ; 7. Polymorphous Condition of the Blood, 8. Remissions, 3 ‘ ‘ e II. Lymphemia, Red Cells, White Cells, Quantitative Gasases Qualitative Changes, é Summary of Blood Changes in Leukemia, . Differential Diagnosis of Leukeemic Blood, Effect of Intercurrent Infections in eulcomis. Hodgkin’s Disease, The Blood, White Cells, Summary and Diagnostic Value, Effects of Splenectomy on the Blood, “Splenic Anemia,” 2 : ‘ : ‘ é PART II. AcutE Inrectious DISEASES. CHAPTER III. INFLUENCE OF FEVER ON THE BLOoD, Pneumonia, . : : : é . (a) Bacteriology of the Blood, - 3 é : (0) Coagulation and Fibrin, (c) Concentration of the Blood, (ad) Specific Gravity, Red Cells, White Cells, a ‘ : ; : : Quantitative Changes, Qualitative Changes, PAGE . 160 . 161 . 161 . 161 - 162 . 163 . 163 . 165 . 165 . 166 . 167 . 168 . 169 . 169 . 169 . 170 . 170 . 171 . 171 . 171 . 172 . 175 . 175 . 177 . 179 . 180 . 180 . 184 . 184 - 185 . 188 - 189 . 189 - 190 . 190 . 190 . 190 . 191 . 192 - 193 TABLE OF CONTENTS. xili PAGE Diagnosis and Prognosis, . : : i ‘ ‘ 2 . 195 Broncho-Pneumonia, . é é ‘i ‘ é ‘ ‘ a . 197 Typhoid Fever, . ‘i : . 7 : : . 0 . 197 Bacteriology of the Blood, . : : i. . : ‘ . 197 Quantitative Changes, . - ‘ 7 s . . . . 198 Red Cells, : : < ‘ ‘ é s é 7 . 198 Hemoglobin, ain Re ey Ewe Ge e200 Leucocytes, . : ‘ 5 ‘ 7 . . é 3 . 200 Complications, : , é F é ‘ 3 . 203 Qualitative Changes, . s . . : - , . 206 Summary and Diagnostic Value, . é 7 ‘3 4 - . 207 Prognosis, . ¥ 7 3 é ‘ 7 - 7 : . 209 Diphtheria, . ‘ - $ ° - ‘ 3 ‘ . 3 . 210 Red Corpuscles, . ‘ ‘ . P es ° 3 5 . 210 Hemoglobin, i . 3 7 i ‘ , 5 : . 211 White Corpuscles, 5 : é 3 : , ‘ 3 . 211 Summary, . . : i 3 ‘ . 3 ‘ . . 218 CHAPTER IV. Acute Inrectious Diszaszs (Continued). Scarlet Fever, : 3 ‘ ‘ 2 - 3 : - - . 215 Red Cells, . ? : : : ‘ : ‘é a a . 215 White Cells, . 3 ss A ‘ 7 i é ‘ : . 215 Summary, . : . ‘ A é ¥ ‘i é ¥ . 216 Diagnostic Value, - : z 3 z 2 ‘ 3 . 217 Measles, Rotheln, and Mumps, . . 7 : : ; . 217 Whoopiug-Cough, ‘ i 3 i F ‘ : r § . 218 Small-pox (Variola), . ‘ , : 3 3 ‘i ; 3 . 219 Chicken-pox, , : 3 4 : 2 . * . 221 Acute Articular heamndiien, 5 ‘ 3 5 5 - ‘ . 221 Fibrin, Alkalinity, Red Cells, : : : : » 221 Qualitative Changes, Hemoglobin, Lencocytes, ; F A » 222 Summary and Diagnostic Value, . ‘ . 4 6 . » 225 Asiatic Cholera, . F é F : u 2 ‘ ‘ : . 226 Erysipelas, . ‘ é : . p ‘ a 3 é . 227 Tonsillitis (Follicular), . $ é 7 < 5 3 - . 228 Grippe, ‘ ‘ a Fi . 7 . 3 . . ‘ . 229 Septiceemia, : Q ‘i Fi : : 3 ; . 230 Bacteriology of the Blood, é 5 : : . , 231 Red Cells, - 3 - . ‘ * : 3 : . 232 Leucocytes, . 3 . 3 $ . - . . 236 Summary and Hieenestie Value, z F z 7 ‘ 3 . 237 Abscess, Iodine Reaction in, > ‘i . . 7 < : . 239 Appendicitis, ‘ : . - - ‘ : 5 3 ‘ . 240 Leucocytosis, - : : : : . ; . 243-246 Differential Diagnosis, . é 3 3 ‘i é ‘ : . 246 Xiv TABLE OF CONTENTS. Pus Tube, Pelvic Abscess, and Pelvic Peritonitis, Differential Diagnosis, . Otitis Media, Osteomyelitis, Other Abscesses, Diagnostic Value, Gonorrhea, Yellow Fever, Typhus Fever, Malta Fever, Glanders, The Bubonic Plague, Actinomycosis, Epidemic Dropsy, Tetanus, J Beri-beri, , Relapsing Fever, . CHAPTER V. DisEases AFFECTING THE SEROUS MEMBRANES, Serous Pleurisy, z : Summary and Diagnostic Value, : Purulent Pleurisy Un: Peritonitis, A Diagnostic Value, Pericarditis (with Effusion), Diagnostic Value, Meningitis, : Epidemic Cerebro- Spinal Meningitis, Diagnostic Value, 3 3 PART III. Curonic InrEcTIOUuS DISEASES. CHAPTER VI. TUBERCULOSIS, SYPHILIS, AND LEPROSY, Tuberculosis, . Red Corpuscles and Hemoglobin, (a) Quantitative Changes, (6) Qualitative Changes, Leucocytes, Changes in Phthisis, Changes in Bone Tuberculosis, Changes in Acute Miliary Tuber culosis, PAGE . 248 249 250 251 251 . 252 . 253 . 253 . 254 205 . 255 256 . 256 . 256 . 207 . 258 . 258 . 209 . 259 . 261 . 262 . 264 . 265 - 265 . 266 . 266 . 267 . 268 . 269 . 269 . 269 . 269 . 270 » 271 . 271 275 . 297 TABLE OF CONTENTS. xv PAGE Changes in Tuberculous Peritonitis, . . : . . 280 Changes in Tuberculous Meningitis, . . . . . 282 Changes in Tuberculous Pericarditis, . . . : . 285 Changes in Tuberculous Pleurisy, é . . ‘ » 285 Changes in Glandular Tuberculosis, . . . . 285 Changes in Genito-Urinary Tuberculosis, . : . - 286 Syphilis, : . ‘ ‘ . . 286 Changes in Red Cells and Hemoglobin, . ° . . . 286 Justus’ Reaction, . 5 7 : ‘ . . 288 Changes in White Cells, 3 7 - . . : . . 289 Diagnostic Value, . : 5 8 6 © 6 ~—. 290 Leprosy, . : - * : Pe ee ee re ee ee | PART IV. DIsEASES OF SPECIAL ORGANS. CHAPTER VII. DISEASES OF THE DIGESTIVE APPARATUS, : * A * . . 292 Diseases of the Stomach, . 3 ° . A . 7 e . 293 Anorexia Nervosa, " $ a ‘ j a a s . 293 Gastric Ulcer, i ‘ 5 é ‘ : i. . 293 Acute Gastritis and espe pein, és ° . 7 . ‘ . 298 Chronic Gastritis, . d ‘a ‘ ‘ * ‘ . 299 Hyperacidity and Hyperseretion, . . . . . . 300 Dilated Stomach, . ts - ” é : : . 3800 Corrosive Gastritis, 7 ¢ : ! . : a s . 801 Diseases of the Intestine, . . a ‘ 3 . 801 Influence of Saline Catharties on the Blood, . 3 : . 801 Acute Enteritis, . 3 ‘ : z S i . % . 301 Chronic Diarrhea, : * 2 ‘ ‘ : F - . 802 Intestinal Obstruction, . 3 : 3 5 . : é . 804 Diseases of the Liver, . F J ‘ ‘ s ‘ ‘ Fi . 804 Catarrhal Jaundice, . - é 5 ‘ ‘ . 304 Qualitative Changes of Red Cells, 5 . . 7 . . 306 Summary and Diagnostic Value, . 7 . é 7 . . 306 Cirrhosis of the Liver, . : . 307 1. Ordinary (Atrophic) Cirthosis without Ji panties: ‘ . 807 Qualitative Changes, ‘ : ; i : ‘ . 307 Hemoglobin, . : : : : 7 5 . . 309 White Cells, . : ; : ‘ . 309 2. Hypertrophic Cirrhosis rt Taundiee, : ‘ . . 310 Red Cells and Hemoglobin, . . . ; . . 810 White Cells, . ‘ ‘ @ . . - . . 310 Diagnostic Value, 3 ‘ ‘ é oi ‘ . ail Xvi TABLE OF CONTENTS. PAGE Hydatid Cyst of the Liver, . op BS @ fer ss . il Acute Yellow Atrophy of the Liver, . . « ‘ . 311 Phosphorus Poisoning,. . . . «© © « « . dit Cholemia, . 3 ; . * ‘ ° 7 ‘ . 812 Gall Stones, . ‘ 3 é . ‘ i. . ‘ ; . 812 Cholangitis, . . . . « «© «© «© «© ~ «814 Abscess of the Liver, . ‘ = ‘s e é . . . 815 Cancer of the Liver, . : a ; é 5 $ . . 815 Gumma of the Liver, . ‘ 3 ‘ a ‘ . . . 815 Hemorrhagic Pancreatitis, . é F . . 7 . . . 315 Diseases Affecting the Heart, . F . ‘i . : . . 316 Pericarditis, . is é si s : is C . . 316. . Endocarditis, . i . . : 3 ‘ . 316 Ulcerative Endocarditis, ; "i ‘ F ; * . 816 Red Cells, 7 s . . a : i . s . 316 White Cells, . . . 5 ; j 5 ‘ ‘ . 317 Diagnostic Value, . ‘ : . * e e s . 319 Myocarditis, . ‘ 5 . 7 . . . . . - 820 Valvular Heart Disease, 3 ‘ . ‘ ‘ ‘ . . 820 Red Cells, : . . . : . 7 : . . 821 White Cells, . ; ‘ . : : ‘i ss 2 . 822 Congenital Heart Disease, . . . . . . é . 823 Aneurism, . . . . . . . . ie . 3826 Diseases of the Kiduays, z ‘ és e 7 : 5 ‘* . 827 Acute Nephritis, . : . . s . . fs - 827 Red Cells and Hemoglobin, 5 . : ‘ . B27 White Cells, . 2 , . 829 Chronic Diffuse and Chronic ‘Parenchymatous Nephritis, . . 829 Red Cells and Hemoglobin, . : - 7 s ° . 329 White Cells, . ‘ 2 ‘ s ‘i é ‘3 . 331 Chronic Interstitial Nephritis, : . . ; ; . . 333 Pyelo-nephritis, . . : - : . . é 7 . 335 Stone in the Kidney, . e A . . : ie . . 335 Diagnostic Value, . m . . . < . . 337 Floating Kidney, . = . . . . . . 5 . 337 Pyonephrosis, : . . . . . . . . . 337 Diseases of the Lungs, 7 . a . . . 3 : . 337 Bronchitis, . é . . . . . . . sj . 887 Acute Bronchitis, . . . . ° < . . . 338 Chronic Bronchitis, ‘ . . . . . . . 339 Emphysema and Asthma, . . . . . . e . 840 SyphilisoftheLung, . . .« .© «2. «.« «.« « . 842 TABLE OF CONTENTS. xvii PART V. DisEAsEs oF THE Nervous System, ConstituTionaL DiszEasszs, AnD Hrmorruacic DIsEAsEs. CHAPTER VIII. : PAGE DisEAsEs OF THE NERVOUS SYSTEM, . 3 ‘ 3 - 5 3 . 3843 Neuritis, é . - ‘ : : 3 i . ‘ . 848 Diseases of the Brain, ‘ ‘ ‘ ‘ ‘ 4 ‘ 3 : . 344 Chorea and Tetany, . . e F : e a . . 346 Diseases of the Spinal Cord, ' ‘ : s ° ‘ : . 346 General Paralysis of the Insane, . ; 5 ‘ . A . 346 Hysteria and Neurasthenia : Hy pochondriasis, - é ‘ 3 . 847 Mental Diseases, . ‘ ‘ $ 3 . 7 : j 3 . 848 Constitutional Diseases, . 3 : . < 5 : 2 P . 349 Obesity, 5 3 é ¥ . é 4 - . 3 é . 349 Diabetes, ‘ z . - ‘ > ‘ 5 é : 3 . 849 Red Cells, . s : 5 : - : 5 . J . 350 White Cells, . . - . . . F : s e . 850 Gout, . : 3 : s . : ‘ ‘ 3 5 ¢ . 851 Myxcedema, . é . = ‘ 3 ‘ 7 . é “i . 351 Cretinism, . : ‘ ‘ ‘ 3 ‘ : i 7 . 353 Graves’ Disease, . 3 ‘ ‘ ‘ ‘ 2 3 7 ‘ . 353 Addison's Disease, 3 " ; 3 . 3 : . 3 354 Osteomalacia, ‘ ‘ : . . : . , F 5 . 895 Rickets, é : - “ - : 3 : 2 ‘ . 356 Red Cells, 5 3 2 ‘ - - ; . ‘ 356 White Cells, . é 3 . : - 3 3 : ‘i . 356 Qualitative Changes, . ‘ 5 . 3 ; . a . 357 CHAPTER IX. Bioop DrEsTRUCTION AND HEMORRHAGIC DISEASES, ss ‘ . 358 Purpura Hemorrhagica, 3 ‘ 7 c : . . . 885 Scurvy and Barlow’s Disease, ‘ ‘ ‘i ‘ ‘ ‘ . 309 Hemophilia, . 7 , A i A ° : * . 359 Blood Destruction, 3 s . i 5 360 Hemoglobinemia in Infectious Diseases, x : . . . 360 Paroxysmal Hemoglobinemia, . . : 3 : : 360 Blood Examination, : 4 ‘ ‘ 3 si : ‘ . 361 Burns, Snake Poison, etc., . ‘ i P 361 Poisons, Chlorate of Potash, Antipyretie, én, by 3 s . 361 Illuminating Gas, . : : , * : 7 . 364 Tansy Poisoning, . , ‘ - . ‘ 7 - . 365 Corrosive Poisoning, . . ‘i . s : . ‘ - 865 XVili TABLE OF CONTENTS. Opium Poisoning, . Ptomain Poisoning, Acute Alcoholism, Plumbism, ; Sunstroke and Heat Hehaustlon, PART VI. Matienant DisEAszE, BLoop PARASITES, AND INTESTINAL PARASITES. CHAPTER X. MALignant DIskaseE, The Blood as a Whole, Cancer, . Red Cells, Quantitative Chanaeg, Hemoglobin, i ‘ Regeneration of Blood. sitter Operations on Cancerous Growths, Qualitative Changes i in Red Cells, . White Cells, : Quantitative Changes, Influence of Position and Size of amon Influence of Individual Constitution, In Cancer of the Breast, In Cancer of the Stomach, 5 Digestive Leucocytosis in Gastric Caneen, Effect of Metastases in Gastric Cancer, In Cancer of the Gullet, . In Cancer of the Liver, In Cancer of the Intestine, In Cancer of Omentum and Abdominal Organs Generally, In Cancer of the Kidney, In Cancer of the Uterus, In Cancer of other Organs, Qualitative Changes in the Leucocytes, Sarcoma, Red Cells, Hemoglobin, White Cells, Qualitative Changes of Leueoeytes, Summary, j Diagnostic Value, PAGE . 865 . 366 . 366 . 867 . 368 . 370 370 . 870 . 870 . 871 373 73 375 . 877 . 377 377 . 378 . 879 380 . 382 383 . 384 . 385 386 . 387 . 888 389 390 . 891 394 894 396 . 896 389 . 899 . 400 TABLE OF CONTENTS. CHAPTER XI. BLoop PaRasITEs, j Examination for the Plasmodium Malarie and Its Products, Time for Examination, . Method of Examination, The Malarial Organism, Recognition of Hyaline Forms, Pigmented Forms, . Segmentation, Comparison of Tertian and Estivo- Aeataqanal Rings, Crescentic Bodies, Flagellate Bodies, Pigmented Leucocytes, Staining the Malarial Organism, Other Changes in the Blood, i Red Corpuscles, Hemoglobin, White Cells, Malarial Hemoplobinemis, ° ‘ . ‘ 3 Typhoid Fever and Malaria, . é A . . CHAPTER XII. DISEASES DUE TO ANIMAL PARASITES, a 5 3 - Filaria Sanguinis Hominis, . ~ : 7 . Spirochete of Relapsing Fever, Technique of Examination, Distomum Hematobium, ms Anemia due to Intestinal Parasites, Bothriocephalus Anemia, Ankylostomiasis (Uncinariasis), The Blood in Gross, Quantitative Changes, Red Corpuscles, ‘ 3 ‘ 5 White Corpuscles, . 3 : . $ Hemoglobin, Qualitative Changes, Red Corpuscles, : . : Normoblasts and Megaloblasts, ‘ 3 : . White Corpuscles, Trichinosis, 5 Summary and Diagnostic Value, : Other Intestinal Worms, CHAPTER XIII. DISEASES OF THE SKIN, ; ; : : 4 , ‘ i Dermatitis Herpetiformis, . ‘ : A * ‘ xix PAGE . 402. . 402 . 402 . 402 - 404 . 404 . 405 . 406 . 407 . 408 . 409 . 410 . 411 . 414 . 414 . 415 « 415 . 416 . 416 . AT . 417 - 422 - 422 . 426 - 426 . 426 . 428 . 429 . 430 . 480 . 481 . 431 . 431 . 431 . 481 . 482 . 434 . 440 . 440 - 442 . 442 xx TABLE OF CONTENTS. PAGE Herpes Tonsurans, é 3 3 : 3 5 : : % . 448 Chronic Eczema, . : ‘i ‘ : ‘ < : . . . 443 Scleroderma, ‘ é - 3 3 ‘ : ; . 448 Psoriasis, . ‘ : 5 é - - . ‘ 2 . 443 Pemphigus, . 5 3 ‘ i j ‘ ‘ s 3 . 444 Lupus, . : j ‘ ‘ é , a : i - 3 . 444 CHAPTER XIV. THE BLoop 1n InFancy, . : ‘ ‘ 5 5 ‘ 3 - . 445 General Characteristics, é ‘ F : : 7 . : . 445 The Anemias of Infancy, . é . : 3 . é 2 . 447 Classification,. ‘ s ‘ ‘ - é - : s . 448 Secondary Anemias, . : ? , ‘ - ‘ ‘ . 448 Qualitative Changes, . é ‘ ‘ 7 . . 449 “ Anemia Infantum Pseudoleukemics,’ We og 7 F . . 450 Importance of the Term, . 5 Fi % 3 : . 452 Pernicious Anemia in Infancy, . . ‘ - . 3 . 454 Polymorphous Condition, . ‘ . A . . . . 456 Leukemia in Infancy, . j 3 ‘ ‘ ; 7 . . 456 PART VII. EXAMINATION OF THE SERUM. CHAPTER XY. THE CLumP REAcTION, ‘ ‘ 2 z . 3 : . . 458 General Description, . : . ‘ : s j 3 2 . 458 Technique, . é _ ‘i ‘ " 5 3 . 460 The Body Fluids Used, é : : - r 3 . 460 Use of the Whole Blood—Fluid, . 3 7 ‘ ‘ 5 . 460 Use of the Whole Blood—Dried, . é 3 i ‘ 3 - 461 Use of the Fluid Serum, ‘ . . 461 The Cultures of Typhoid Bacilli a be Used, ‘ ‘ . . 462 The Use of Suspensions instead of Cultures, % 3 4 . 468 The Use of Attenuated Cultures, . ‘ 3 ‘ 7 ‘ - 463 Dilution and the Time Limit, : . : . . : . 463 The Microscopical Examination, : 3 ‘ - ‘ 3 . 464 General Statistics, . 3 ‘ 3 é : . 464 How Early does the action Appear? : : 7 : . 464 How Late does the Reaction Last? 5 $ < . é 465 The Intensity of the Reaction, . 7 : . . ‘ . 465 Control Cases, ‘ 7 : “ ‘ - . 465 Summary of Clinical Rvidencs, F 2 3 é ‘ . 466 TABLE OF CONTENTS. Xxi PAGE Sero-Diagnosis of Other Diseases, é * . . ‘ a - 466 Cholera, . ‘ 7 . , 7 7 5 . . 466 Malta Fever, . i - F s . . j 7 ‘ . 466 The Bubonic Plague, . fs 7 : . 467 AppeNDIx A. Neusser’s Perinuclear Basophilic Granules, , 5 . 469 APPENDIX B. Statistics in 121 Cases of Pernicious Anemia, . é - 470 APPENDIX C. Red Cells in Chlorosis, " ‘ a 3 ‘ . . 483 APPENDIX D. Leucocytes in Trichinosis, . ‘ 3 ‘ : : - 484 BIBLIOGRAPHY, . . ‘ : . ; < ‘ s £ . 487 INDEX, ; : ‘ ‘ s 7 e * : ‘ : ‘ - 491 BOOK TI. INTRODUCTION. SCOPE AND VALUE OF BLOOD EXAMINATION. Hamaro.oey has now established for itself a definite field of usefulness in the practice of medicine. It has solved some prob- lems where least was hoped from it, and given us disappointingly little help where great expectations had been aroused. We might have expected from it some light on the nature of rheumatism, fu- runculosis, uremia, diabetes, but none has come. On the other hand, who could have hoped that it would help us in the diagnosis of central pneumonia, of deep-seated suppurations, and of trichinosis, or in the prognosis of relapsing fever or of pneu- monia? There are probably not more than five or six diseases in which the blood examination gives us the diagnosis ready-made, but there is a very considerable number of conditions in which the blood ex- amination will help us to make it. Not pathognomonic signs, but links in a chain of evidence are what we are to expect from blood examination. Very often the simple discovery that the blood is normal may be a fact of the greatest value in diagnosis. On the whole it seems to me that the examination of the blood gives evidence similar in kind and not much inferior in value to that obtained by examination of the urine. Both methods of ex- amination give us («) a ready-made diagnosis in a few diseases; (0) side lights on a good many obscure conditions; and (c) the fre- quently great assistance of a negative report. In certain wards of the Massachusetts General Hospital it has been for some years the rule to examine the blood of every patient as a matter of routine at the time of entrance. In asmall proportion of cases this gave negative evidence only; in a much larger proportion it materially assisted in the making of a diagnosis. Improvements in technique have lessened the labor and increased the accuracy of blood examination. The most important facts 4 INTRODUCTION. about the blood of nearly every case can be obtained by a practised observer in fifteen minutes. The blood is the only tissue that we can study easily during the life of the patient. Its relations to all other tissues are such that it is typical of them all in a way that no other tissue is, acting on all and being acted on by all. As yet we have studied chiefly its. morphology, and from that single aspect obtained most of the clini- cally valuable information which we possess about it. But the field of the blood chemistry is in many respects even more promis- ing at the present time, and there seems reason to believe that the study of the blood is still in its infancy and will take a higher place in the future as an aid to diagnosis, prognosis, and treatment. Like all methods of physical examination it has especial useful- ness when we cannot communicate with a patient, either by reason of his unconsciousness, stupidity, or insanity, or because he speaks no: widely used language. In such cases the detection of marked anze- mia, leucocytosis, eosinophilia, a typhoid serum reaction, or a mal- arial organism may be of great assistance. Malingering is made more difficult by it, and in the differentiation of organic from func- tional disease it is often very helpful. There is no febrile disease on which it may not throw light. The evidence for these and many other aids furnished by the blood examination in clinical work is given in the later chapters of this work. PART LI. METHODS OF CLINICAL EXAMINATION OF THE BLOOD. CHAPTER I. ConFinine ourselves to the clinically available processes by which we can gain information of diagnostic or prognostic value, blood examination at the present time embraces the following proc- esses. 1. Estimation of the total volume of the blood and of its oxygen capacity. 2. Examination of the fresh blood (with or without a warm stage). Counting the red and the white corpuscles. Estimation of the amount of coloring matter. Examination of dried and stained specimens. Bacteriological examination of the blood. Examination of the serum.’ . Estimation of the coagulation time. Less important are: 9. Estimation of volume of corpuscles and of plasma in a given quantity of blood. 10. Estimation of the specific gravity of the blood. 11. Estimation of the number of blood plates. 12. Estimation of the amount of fibrin. To describe these processes in detail is the purpose of the next chapters. DAD ME ow J. Estimation oF THE ToTAL VoLUME oR Mass or Buioop. Until the present year the determination of the total mass of the blood has been practically beyond our reach, and our blood exami- nations have dealt wholly with small “samples” drawn from the 1See Chapter xiii. of Book IT. 6 CLINICAL BLOOD EXAMINATION. periphery and treated as typical of the rest without regard to any possible variations in the total amount of blood in the vessels. But recently Haldane and Smith, in three important and inter- esting papers,‘ have suggested and applied a method which, if it stands the test of time and criticism, will add very materially to our knowledge of blood physiology and blood pathology. The essential features of their method are as follows: 1. The patient inhales a measured volume of CO (a harmless and not unpleasant process). After two or three minutes a few drops of blood are taken for analysis and the percentage to which the hemoglobin has become saturated with carbonic oxide is esti- mated (by the carmine method, see reference at foot of page). 2. Knowing the amount of CO inhaled, and the degree in which the blood has become saturated by this known amount, the quantity of CO capable of being taken up by the whole of that patient’s blood can be calculated. Thus, supposing that the volume of car- bonic oxide delivered was 150 c.c., and that the blood was twenty- five per cent saturated, it is obvious that the blood would have been one hundred per cent saturated by 600 c.c. Its total capacity for CO (or for oxygen) is 600 ¢.c. 3. How then shall we connect this estimate of total oxygen capacity with the volume of the blood? In a previous research the writers showed that the oxygen capacity per 100 ¢.c. of any given sample of blood can be accurately estimated by comparing its color with the color of an equal sample of ox blood whose capacity for oxygen has been previously determined. For example, a patient having absorbed 100 ¢.c. of CO, itis found that his blood is one-fifth saturated by this gas. The total capacity for CO (and so for oxy- gen) is therefore 500 c.c. But further, the patient’s blood is found to have the same color as an ox’s blood every 100 ¢.c. of which has been previously determined to be capable of taking up 20 c.e. of oxygen. The patient’s total oxygen capacity (500 c.c.) divided by the oxygen capacity of every 100 c.c. of his blood (20) gives us 25. This figure is then the number of hundreds of cubic centi- metres of blood in his body—2,500. Smith has now applied this method to over one hundred cases, and found it to produce no appreciable ill-effects on the patient. As the result of these studies, he estimates the average volume of 14. Journal of Physiology, xxii., p. 232. 2. Journal of Physiology, p. xxv., 331. 3. Transactions of the Pathological Society, 1900, vol. li. METHODS OF CLINICAL EXAMINATION. 7 blood in health as 3,240 c.c. or 3,420 gm. The latter figure is obtained by means of the average specific gravity of normal blood (taken as 1.055). In the fourteen normal cases studied the blood mass varied from 2,830 to 4,550 gm. or 41, to 7, the body weight, but was never as large as had previously been estimated (,!,). In chlorosis, Smith found that the apparent diminution in he- moglobin was, in fact, due to the great increase in the plasma of the blood (serous plethora), the total oxygen capacity or heemoglobin remaining normal. In pernicious anzmia, on the other hand, the amount of plasma is sometimes increased and sometimes dimin- ished, but the oxygen capacity or hemoglobin is always low. These observations will be referred to again later (see p. 131): II. ExamMiInaTIon OF THE FRESH BLoop. (a) Puncture.—In all the processes about to be described (ex- cept the bacteriological examination) the first step is as follows: Gently cleanse the lobe of the patient’s ear with a damp cloth and then dry it. All vigorous rubbing or kneading is to be avoided. Attempts to sterilize the skin or to cleanse it with alcohol and ether are a waste of time. A small lancet or a bayonet-pointed surgical needle may be used; a sewing needle gives more pain and draws less blood from a given depth of puncture. A steel pen, with one nib broken off, makes a good lancet. The needle need not be sterile. In several thousand blood counts made at the Massachusetts Gen- eral Hospital since 1893 the needles have never been sterilized and no signs of sepsis have been seen in any case. Possibly this is due in part to the fact that the next step in the process after the puncture has been made is always to wipe away four or five successive drops as they emerge. This serves not only to get the blood flowing freely, but also to wash the ear in its own blood. The puncture is best made into the lower surface or edge of the lobe, which is steadied with the fingers of the left hand. A very quick stroke gives least pain, the hand rebounding like a piano hammer. If the skin of the lobe is stretched tight with the fingers of the left hand so that no “give” is possible, the quick puncture gives hardly any pain. I have repeatedly taken blood from a sleeping child without waking it. What hurts the patient is the mistaken tenderness that slowly presses the needle through the skin. 8 CLINICAL BLOOD EXAMINATION. The puncture must be deep enough to make the blood flow freely and without pressure, after it is once started by pressing out a few drops. Blood squeezed out with pressure should never be used for counting, as it may be considerably diluted with fluid pressed out of the neighboring tissues. If the skin is moderately thin and the ear easily made hyperemic, a puncture one-eighth of an inch deep is sufficient. With thick, bloodless skin it may be necessary to go in one-quarter or one-third of an inch—never more. Beware of bleeders. I have seen bleeding from a puncture made for a blood count which could not be checked for three-quarters of an hour. It is always safer to ask after a history of hemophilia as a matter of routine before taking blood, just as one asks after false teeth before etherizing. If there is a history of hemophilia, a mere touch of the needle point will give us all the blood we need without embar- rassing us with a troublesome hemorrhage. There is no question as to the superiority of the ear over the finger for drawing the drop. The ear is less sensitive than the finger, and a slighter puncture gives us all the blood we need. Moreover, it is a distinct advantage, especially in children, that the patient cannot watch the puncture of the ear, or the preparations for making it, and cannot easily withdraw the part. A sleeping patient often needs to be roused to get at his finger, while his ear is usually easily accessible above the bed clothes. Again, the absence of any bony prominence against which to press makes us less likely to use too much pressure than if we puncture the finger. When one is making frequent examinations of the blood of a sensitive person, as in pneumonia, these details are of real impor- tance, and in cases of pernicious anemia in which the previous attempts to get blood from the finger had been absolute failures, I have found no difficulty in getting it from the ear. In this disease the advantages of the ear over the finger are peculiarly great. Preparation of Temporary Specimens for Immediate Examination. (6) When, after wiping away the first four or five drops, a good- sized drop exudes spontaneously, touch the centre of a perfectly clean cover-glass against the summit of the drop without touching the skin itself at all, and drop the cover-glass face downward upon a slide so that the force of the impact will help to spread the drop of blood thinly and evenly between slide and cover. It is recom- mended by Ehrlich and others to hold the cover-glass with forceps, METHODS OF CLINICAL EXAMINATION. 9 but there is no harm in holding it with the fingers, provided we avoid touching either of its surfaces, i.e., hold it always as in Fig. 1. Slide and cover must be perfectly clean, else the blood will not spread out in a layer thin enough to avoid the corpuscles overlying each other so that not one of them is clearly seen. Further, as dirt simulates fairly closely some of the pathological ap- pearances for which we are on the look- out, its presence on the slide leads to loss of time or to mistaken conclusions. Cover- glasses, as they come from the shops, may be coated with a substance not easily to be removed. To get them really clean nothing is so simple as or more effective than soap and water. After several years’ use of the method of cleaning usually advised (viz., strong mineral acid, followed by alcohol and then by ether), I have become converted to the use of plain soap and water as the best and simplest way of cleaning slides or cover-glasses. Rub soap over every part of the glass, wash it off with water, and polish it thoroughly with a clean handkerchief (most towels are apt to leave a scrap of lint on the glass).? If slide and cover are perfectly clean, are held as in Fig. 1, and allowed to touch only the summit of the blood drop and not the skin, the blood will spread out properly between them, and no pressure on the cover-glass will be needed to make the layer of cor- puscles thin enough. Pressure is undesirable, as it often makes all sorts of artefacts in the preparation and hastens crenation of the red corpuscles. Better results are obtained if slide and cover are warmed just before using, and it is well to have an assistant rub the slide vigorously with a towel just before it is used. This method is, of course, applicable only to specimens to be Fig. 1.—Proper Method of Hold- ing a Cover-glass. 1T am not unmindful of Ebrlich’s warning that the moisture of the fingers spoils the specimen; but in practice I do not find it to be true except as re- gards the margin of the film, the good preservation of which is not essential. Only the thinnest cover-glasses in the market should be used, { inch is the best size. ? Further experience has convinced me that water alone is generally suffi- ‘cient, provided the polishing, which is the chief factor of success, is thorough. ‘Tissue paper is very useful for polishing cover-glasses. After polishing, it is well to pass them though a Bunsen or alcohol flame once or twice. 10 CLINICAL BLOOD EXAMINATION. immediately examined. Specimens which are to be transported or preserved should be prepared as directed on p. 43. Prevention of Cell-Death. Slides so prepared are usually best examined with a one-twelfth oil-immersion lens. Asa rule they keep long enough for purposes of examination without any further precautions, but if we desire to keep the blood fresh and uncoagulated for a longer period, it is best. to exclude air in this way: Paint upon the slide with vaseline, cedar oil, or any gummy substance a hollow square or ring of about. the size of the cover-glass, so that when the latter with its drop of blood is put down upon the slide the drop will spread out inside the ring of oil, which seals the margins of the cover-glass to the slide. Specimens so prepared will keep for many hours unchanged, and without crenation or coagulation, if the weather is warm or if the slide be kept in a warm place. In examining blood suspected of containing malarial parasites it is sometimes useful to put the whole microscope into one of the warming apparatuses devised for the purpose. This is better than any of the various kinds of warm stage in use, but in clinical work there is ‘rarely if ever any need for artificial heating apparatus of any kind, provided the room and the slide are warm. What Can be Learned from Fresh Blood. In the first place we note the readiness or sluggishness of its. flow from a puncture of standard depth. The blood flows more readily than usual in the following conditions: 1 Peripheral congestion or vaso-dilatation. 2. Exaggerated fluidity of the blood (chlorosis, some types of anemia, and hemophilia). It flows sluggishly : 1. After profuse hemorrhage or serous drain (cholera). 2. In certain cases of extreme anemia—e g., emaciated cancer cases. 38. Vasomotor spasm (cold, hysteria, Raynaud’s disease, uremia —certain cases). 4. Exaggerated coagulability Examination of the fresh blood by the method described above METHODS OF CLINICAL EXAMINATION. 11 is also the best way known for ascertaining the presence or absence of— 1. The Plasmodium malariz. 2. The Spirochete of relapsing fever. 3. The Filaria sanguinis hominis. 4, Rouleaux formation among the red cells. It is also a quick and convenient method of finding out with ap- proximate accuracy : (a) Whether the blood contains an increased amount of fibrin; (6) Whether any considerable anzemia or leucocytosis' is present ; (ce) Whether or not the amount of hemoglobin in the red cells is much decreased ; (d) Whether the red corpuscles are deformed ; (e) Whether the “blood plates” are increased or not. <2 a eal 3 encountered in counting is _*o° |oP °° “hoo |? 02 cic ae the presence of a few cor- eels lee | bee of] ooo puscles on or touching one tm oop eotets = or more of the lines bownd- p» _° fo Pol o°o| o 2] 5 of ofa] 9 # ing the space to be counted. ss 0] 2} ° & %} 2° b 6° Belogfo°o Shall we count these out 2 ee pO eg ver or in? Fig. 6.--Field of Thirty-six Squares on Ruled Disc of In counting, for in- Thoma-Zeiss Counter Covered with Normal Blood ‘ Diluted Two Hundred Times. stance, a field like that in Fig. 6, what are we to do with the cells which sit astride the lines AA, BB, etc.? To get round this difficulty, it is best to make it a rule to count in all the corpuscles on or touching some two of the boundary lines (e.g., AA and BB) and to take no notice of any cell on or touching the lines CC and DD. In this way the exclusions just balance the inclusions. Of course all cells within these outer boundary lines are to be counted whatever their position. Beyond this the details must be settled by each man for himself. My own habit. is to count through the squares in the order indicated by the track of the serpentine arrow in the accompanying Fig. 7, and to count by twos or threes. 1Use only water—alcohol dissolves the cement which holds the ruled disc in place. 2 See Reinert’s “ Zihlung der Blutkorperchen,” Leipzig, 1891, p. 48 et seg. 18 CLINICAL BLOOD EXAMINATION. A movable stage makes the counting easier, especially for be- ginners. Either natural or artificial light may be used, with a small aperture diaphragm, and if the instruments are clean and the diluting solution fresh and free from sediment,’ there is no diffi- culty in deciding how many cells each square contains, and no ex- traneous fragments to be excluded. We must dis- tinguish the white corpus- cles from the red, not by their size but by their stain if Toisson’s solu- tion is used, otherwise by their peculiar shining look when the lens is drawn up so as to put the red cells slightly out of focus. The blood plates are not noticeable and - lead to no errors. When the number of Fic. 7.—The Arrow Indicates the Order in which the corpuscles in 360 squares Squares are Counted. has been counted the number is divided by 360 and multiplied by 800,000 (i.e., by 200 to make up for dilution and then by 4,000, because each square is equivalent to z~,, of a cubic millimetre), which gives us the number of corpuscles per cubic millimetre. These figures need not be committed to memory, for we have marked on the instruments used all the data necessary for the cal- culation, z.e., the dilution figures on the pipette and the area and depth of a single square on the counting slide. (e) The importance of cleaning the pipette as soon as the count- ing is done is so great that it should be reckoned as one of the regular steps on every count. First water, then alcohol, and lastly ether must be sucked into the pipette and brought into contact with every part of the bulb and tube. After this air must be sucked or pumped through the tube until it is perfectly dry and the glass ball will roll about freely in the bulb without sticking anywhere. These precautions take but two or three minutes, and if they are 'Most diluting solutions precipitate or accumulate spores, and need to be frequently renewed or filtered. COUNTING THE CORPUSCLRS. 19 omitted and the blood dries in the pipette, it may take several hours’ work to get it clean. Further, if it is not thoroughly dried after cleaning, the mixing of the blood when it is used next cannot be done accurately. The first three steps of the above process (¢.e., the obtaining, diluting, and mixing of the blood) must be done as swiftly as is compatible with accuracy, but when once the blood is mixed in the pipette it can be kept there indefinitely and counted at leisure. None of the corpuscles are destroyed or lost, and if the bulb is thoroughly rolled and shaken up whenever we are ready to count the blood, no error results from keeping it twenty-four hours or more in the pipette. It is not necessary, therefore, to carry a microscope to the pa- tient’s house or bedside; the pipette and the diluting solution are all that we need to take with us, and when the blood is mixed in the pipette, the latter’s ends can be closed with a rubber band, and the blood carried home and counted at leisure. The pipette should be kept approximately horizontal during the transit. CouNTING THE WHITE CORPUSCLES. To make a reasonably accurate count of white corpuscles, using the “red counter” and the dilution of 1:100 or 1:200, we need to count an immense number of squares, far more than was necessary in estimating the red cells—in fact, at least ten times the whole ruled space. It is therefore far quicker and more accurate to use the “white counter” or large-bore pipette with a diluting solution which renders the red cells invisible and leaves only the white to be counted. Such a solution is the one-half of one-per-cent solution of glacial acetic acid in water. With this the white corpuscles stand out very clearly and the red can barely be seen at all. The technique is the same as that already described, with the following exceptions: 1. The drop of blood needed is nearly three times as large as that used in the “red counter”; it is about as big as can be made to stay on the ear without rolling off, even if we draw blood only to the mark 0.5. If we draw blood tothe mark 1, as advised by Tiirck, we must make a deeper puncture and suck in the blood as it flows without waiting for the formation of drops. 2. The bore of the tube being large, it fills and empties more 20 CLINICAL BLOOD EXAMINATION. readily. Hence our suction must be gentler, and it is rather harder to stop exactly at the mark 11. For the same reason the diluted blood will run out of the pipette if the latter is not kept nearly horizontal, and the bottle of diluting solution should accordingly be tipped up as we plunge in the point of the pipette, so that the latter is depressed as little and for as short a time as possible before suc- tion begins. 3. Zappert’s modification of the Thoma-Zeiss counting chamber should be used. Zappert’s counting chamber (now supplied by Zeiss at the same price as the ordinary one, ¢.e., 15 marks) differs from that ordinarily used in that the central square millimetre is surrounded by eight undivided squares of the same size (see Fig. 10). With this ruling one counts first the number of leucocytes in the central square (about 35 in normal blood) and then in each of the surrounding undivided squares. This gives us a total of about 300 leucocytes (in normal blood) as a basis for our calculations. The total so obtained is divided by 9, and then multiplied by 200 (provided we have diluted 1:20). The advantages of the large-bore pipette are obvious. The only drawback is its expanse. The technique is not at all difficult. Counting Both Red and White Cells with the Same Pipette. We may avoid buying both large-bore and small-bore pipettes in one of the following ways: 1. We can count both red and white corpuscles with the “red counter.” 2. We can count both red and white corpuscles with the “ white counter.” The reason why we cannot use the “red counter” for counting white cells, unless modified in some way, is that in the whole ruled surface of the counting chamber not more than three or four white corpuscles are to be found in normal blood when diluted two hun- dred times. If we dilute less, we cannot see the cells distinctly, because they are so crowded. If we find, say, three white corpus- cles as the number to be used as a basis in calculating the number of white cells in a cubic millimetre, the chance of error is very great, the multiplier being so large (2,000) and the multiplicand so small (3). To get over this difficulty we may utilize the cells spread over COUNTING THE CORPUSCLES. 21 the dise of the counting chamber outside the ruled space in one of the following ways: (a) By measuring the field of the objective used. The writer’s objective, No. 5 of Leitz, has a field of very nearly one-quarter of a square millimetre or one-quarter of the whole ruled space. Four fields of this lens, taken anywhere outside the ruled space, there- fore, contain the same number of cells as will cover the whole four -hundred small ruled squares, and when we have counted the white cells in a series of four fields of this lens, we have accomplished as much as if we have put afresh drop upon the counting chamber and counted all the ruled squares over again; the latter process is tedious, the former very quick. Thus it is my practice in some cases to proceed as follows (see Fig. 8): Supposing the large circle CCCC to rep- resent the surface of the small dise (A, Fig. £) in the centre of the counting cham- ber, and AAAA the ruled squares in the middle of this disc, four microscopic fields are taken in the direction away from the centre indicated by circles and arrows in the figure. Starting, say, to the right of the ruled squares with the left edge of the microscopic field just touching the outer boundary line of the squares, count all the white cells to be seen in the field. Then move along to the right till the corpuscles which were on the extreme right of the first field have gone out of sight to the left. Your field is then in the position of the circle marked 2 (Fig. 8). Count all the white cells in this field and so on for four fields. With my objective, four such fields are almost exactly equal to the whole ruled space AAAA. With other objectives of course the number of fields is different. When we have counted four fields in each of the four directions c (e Fig. 8. 22 CLINICAL BLOOD EXAMINATION. indicated by the arrows we have covered as much ground as if we have put four successive drops on the slide after the first one and counted all the ruled squares in each, and we have saved much time and labor. (6) Another and better method of at- taining this same end is as follows: Cut out of black cardboard a piece of the shape shown in Fig. 9 and of such a size that it will fit into the tube of the eye- piece—the square aperture allowing a space of just one-quarter of a millimetre (one hundred of the ruled squares) to be seen through it with a given objective (say Leitz No. 5). Four fields as seen through such an aperture can then be counted in various parts of the slide outside the ruled space as explained above. (c) For any one living where microscopic ruling on glass can be done at a moderate cost, by far the best way is to have the rest a _— Fic. 10.—Zappert’s Counting-chamber. of the disc A (Fig. 5) ruled off as shown in Fig. 10. Leitz and Zeiss now supply instruments so ruled. I have not been able to hear of any one in America who could do such work at a moderate expense. COUNTING THE CORPUSCLES. 23 (d@) We may work out mathematically what number of squares would be contained on the whole disc were it all ruled like the cen- tral portion. This can be done with the aid of a micrometre eye- piece and a mechanical stage. There is some variation in individ- ual instruments, but as a rule the disc outside the central ruled space has an area of about two thousand of the small squares. 2. We may use the “white counter” for red corpuscles in the following way: Suck up blood only to the first mark up from the point (i.e., one-fifth of the usual distance) and then Gowers’ or Tois- son’s solution up to the mark 11. This gives a dilution of 1: 100, and in anemic cases, in which the cells are not very numerous,. answers well. The same pipette can then be carefully cleansed and used for counting white cells with the acetic acid one-third per cent, and a dilution of 1:10 or 1: 20. Whatever method of counting white corpuscles is adopted, we ought to have at least one hundred corpuscles actually counted to. use as the multiplicand of our computation. A single drop from the white counter with a dilution of 1:10 gives us normally about: seventy white corpuscles in the four hundred ruled spaces, and by repeating the process with a second drop the result may be made reasonably accurate. This was the method adopted by Rieder’ in the immense number of counts made by him. IT, Durham’s Modified Hemocytometer. In the Edinburgh Medical Journal for October, 1897, Herbert E. Durham, of Cambridge, England, describes a self-filling capillary pipette which has considerable advantages over the ordinary Thoma- Zeiss instrument. The account of the device is here given in his own words. “The apparatus entails no new principle; it is rather to be con- sidered as an adaptation of anumber of details, which together seem to present some advantages. As in the Gowers’ instrument, there is a separate capillary pipette for measuring the blood, one for measuring the diluting fluid, a mixing vessel, and the counting chamber. A few words may be said about each of these. “ Capillary Pipette.—There is an obvious advantage in the use of a self-measuring pipette. It cannot go wrong by accident. Durham has availed himself of the pipettes introduced by Dr. Oliver, namely, small pieces of thick-walled capillary tube—5 and 1“ Beitrige zur Kenntniss der Leucocytosis,” Leipzig, 1892 (Vogel). 24 CLINICAL BLOOD EXAMINATION. 10 c.mm. in capacity. These are carefully recalibrated by the makers of Dr. Oliver’s instrument—The Tintometer Company. “There is, moreover, another important advantage attaching to Dr. Oliver’s pipette; this consists in the readiness with which it may be cleansed. As he has described, all that is necessary is to pass a piece of darning cotton by means of a needle through the bore of the pipette. All the adherent serum, etc., is completely removed thereby. Durham generally wets the end of the cotton ‘with ether, but this is not absolutely necessary. In passing the needle, it is better to pass it into the pointed end, in case it is not withdrawn perfectly axially, when there is a liability to chip the thinner unsupported glass. “ Any one who has worked much with the Thoma-Zeiss pipette will know how troublesome it is to clean, especially when a number Fig. 11.—Cross- section of Durham’s Automatic Blood-Pipette. TT, Glass tube (like that of medicine-dropper) ; V, rubber nipple (like that of medicine-dropper) ; p, perforation in the nipple; c, cork holder, perforated by capillary pipette. of observations have to be made in a limited time. Unless it is frequently cleaned out with strong acid, there is a tendency for the deposition of sticky serum remains which interfere with true read- ings. 3 “For use, Dr. Oliver’s pipettes are mounted by means of a small cork (ce) in a large glass tube (7'), which is provided with a rubber nipple (1), having a lateral perforation (p) (Fig. 11). “The mixing vessel consists of a small test tube (23 x 7% in. for le.c., or 23 x 3 in. for }¢.c.). Several such tubes may be kept, so that a number of observations can be made if necessary. For thoroughly mixing the blood and diluting fluid, one or more small glass globules are placed in the tube. By using different colored glass globules, different specimens can be readily differentiated. “For measuring the diluting fluid, pipettes containing 1 and 4 ‘e.c. are used; these are remarked at 995 and 990 ce.mm. and 495 and 490 c.mm. respectively. With these graduations the following dilutions may be obtained: 1: 200, 1:100, and 1:50, with the ap- propriate capillary pipette. COUNTING THE CORPUSCLES. 25 “Having measured the diluting fluid, according to the eventual dilution desired, the blood capillary is filled by touching the ex- uding drop of blood and allowing it to completely fill itself. The blood may be obtained in the usual manner from the lobule of the ear, the first drops being wiped away. “The hole in the nipple allows free air-way so that there is no hindrance to the action of capillarity. When filled, any blood on the outside of the pipette is rapidly wiped off, and the tube is in- serted into the mixer until the point is one-half to three-fourths of an inch above the level of the contained liquid. “The nipple is then held in such a way that the hole lies under the thumb of the operator. When this is the case it is slightly squeezed, and then, while the pressure is continued, the bulb is rotated so that the hole is free again. In this way the blood is squirted out, but not sucked back again. The procedure is ex- tremely simple and really requires no practice, given an operator who is not possessed of ‘ five thumbs.’ In order to wash out the remains of the blood the point of the capillary is dropped into the diluting fluid; the bore instantly fills itself. It is then with- drawn and the pressure and rotation of the nipple are repeated. This has to be repeated several times, and occupies a few seconds of time. It has been suggested that a certain amount of error is introduced by measuring the diluting fluid in a pipette, the inner surface of which retains some moisture; this is extremely small in amount if the pipette is emptied slowly, and comparative readings with the Thoma-Zeiss apparatus show that the error is negligible. “To mix the blood and diluting fluid thoroughly, the mixer is placed between the opposed hands, which are rubbed backward and forward; the mixer is rotated thereby, and the glass globules cause a thorough dispersion of the corpuscles in the fluid. “A drop of sufficient size is then placed upon the counting chamber, and the cover-slip is slipped on sideways in the usual way. I prefer the Thoma-Zeiss counting chamber. “The advantages of this method are: “41, The ease and thoroughness with which the pipette can be cleaned. “2. The manifest advantage of the self-measurement of the blood. “3. The avoidance of the objectionable necessity of using the mouth to suck fluids into the pipette. 26 CLINICAL BLOOD EXAMINATION. “4, The measurement of the diluent can be done carefully and calmly beforehand, and any error corrected without taking any more: blood. “5, The greatly smaller cost of the pipette. “6. The same pipette is useful for making various dilutions in serum diagnosis, by using several mixing vessels filled beforehand with dilute fluid.” CHAPTER III. \ OLIVER’S HAMOCYTOMETER—CENTRIFUGALIZING THE BLOOD —HAZMOGLOBIN ESTIMATION—SPECIFIC GRAVITY— STAINED SPECIMENS—BACTERIOLOGICAL EXAMINATION. OuIveR’s H#MOcYTOMETER. ReEcENTLY a method of estimating corpuscles by means of their optical effect, and without directly counting them, has been intro- duced by Dr. Oliver. For practical purposes an actual counting of the corpuscles must be considered a necessity; not only since the number of leucocytes is not without importance (e.g., in the diag- nosis of enteric fever), but also since these cells may be so abundant that they may interfere with the use of optical methods, as in the case of leukemia. Nevertheless the instrument is very accurate and useful in many cases. Its principle is based on the fact that if a small quantity of blood is gradually diluted with Hayem’s solu- tion’ in atest tube whose sides are flattened so that its mouth forms a rectangle about 15 mm. by 5 mm., and a candle flame is looked at through the mixture, there is to be seen, when a certain degree of dilution is reached, a bright horizontal line on the glass. This line is made up of a large number of minute images of the flame, pro- duced by the longitudinal striation of the glass. If the quantity and quality of blood used are in every instance the same, the degree of opacity depends wholly on the amount of Hayem’s solution added. It is found that with normal blood the amount of diluting solution necessary to allow the image of the candle flame to be seen through the mixture is always the same, and can be very accurately fixed, so that a variation of one per cent in the number of corpuscles can be distinguished by noting the amount of diluting solution which must 1 Hydrargyri perchloridi...............0. 0c eee eee 0.5 gm. SOC CHOTI Aires ec cnteeeSeaac cece eae ee tts 1.0 “ © “GOI PNAS eis Seated date tee eadatneled 5.0 “ Aquee destillate...... 0... cece ec cece ee eee eens 200.0 c.c. 28 CLINICAL BLOOD EXAMINATION. be added before the image of the flame appears. To collect the blood, Oliver uses a capillary pipette containing about 10 c.mm. (one large drop), and used exactly in the same way as the v. Fleischl capillary pipette (see Fig. 12). One pipette full of normal blood is gradually diluted in the flat- tened tube with Hayem’s solution until a bright horizontal line Fie. 12.—Oliver’s Heemocytometer. A, Graduated mixing tube; P, capillary pipette; M, dropper, with rubber nozzle fitting the capillary pipette. caused by the image of candle flame becomes visible through the mixture. The point to which the column of the mixture then reaches is marked 100, and the space between that point and the bottom of the tube is divided into 100 equal parts. The point marked 100 is then equivalent to 5,000,000 red corpuscles; 90 = 4,500,000, 80 = 4,000,000, and so on, each degree on the scale corresponding to a difference of 50,000 corpuscles (Fig. 12), Use of Oliver's Hemocytometer. The capillary pipette is first thoroughly cleaned and dried by passing through it a needle and thread saturated with water and then with alcohol and ether. It is then filled in the usual way, OLIVER’S HAZ MOCYTOMETER. 29 and the outside carefully and quickly wiped if necessary. The medicine dropper (previously filled with Hayem solution) is then connected with the polished blunt end of the pipette by means of the rubber tube (Fig. 12), and blood washed into the test tube. Speed is essential, else coagulation occurs. If the previous hemo- globin estimation has shown ninety to one hundred per cent of color- ing matter, we can safely add the diluting solution rapidly until the point marked 80 is reached. If the coloring matter is lower we must cease our rapid dilution correspond- ingly sooner. When we get near the point at which the flame image is likely to appear, the diluting fluid must be added a few drops at atime. After each addi- tion put the thumb over the mouth of the tube and turn it upside down once or twice to mix the blood thoroughly, wiping the thumb each time on the edge of the tube so as to put back what fluid has ad- hered to it. At a certain point the image will sud- denly become visible. It is seen soonest if we rotate the tube on its long axis, Fic. 13.—Showing the Method of Holding Oliver’s Hemocytometer. as the image becomes visible earliest at the sides of the tube, but dilution should be continued drop by drop until the horizontal line of light is just visible across. the short diameter of the tube. The appearance of the incomplete line at the sides is a constant forerunner of the complete transverse line, and should put one on one’s guard as very close watching is needed to recognize it without overstepping the necessary dilution. The opacity remains uniform for many minutes. The whole process. should be carried on in a perfectly dark room, and the diffused light. of the candle must be shut off from the eye. This is best done by 30 CLINICAL BLOOD EXAMINATION. fitting the tube into the hand as shown in Fig. 13 with the long axis” in line with candle, holding the tube close to the eye, and standing about ten feet from the candle. In the use of both of his instruments Oliver employs only the small wax candle known as Christmas can- dles, whose flame is of the most convenient size. After some experience with this instrument I find it simple, accurate, eye-saving, and rapid. The whole test can be made in five minutes. Its only drawback is the impossibility of making any estimate of the white corpuscles with it. Dr. David D. Scannell made in 1899' a series of observation on patients in my clinic, to test the accuracy of the instrument when compared with actual counts made with the Thoma-Zeiss apparatus. As will be seen by the accompanying table, his results showed that, exclusive of leukemic cases, the difference in the readings of the two instruments was from 4,000 to 74,000 red cells, an average of 35,000. This imples an error of less than one per cent, granting that the Thoma-Zeiss No.] Dingnosis. (| THoIaZetse) Olivers hemocytometer | Remarks, 1 | Pernicious anemia. .| 1,704,000 | 32 per cent.! 1,700,000 2 | Debility (?)........ 4,368,000 | 87 “ 4,350,000, 38 | Normal............ 4,626,000 | 92 * 4,600,000 4 | Leukemia......... 2,492,000 | 52“ 2,600,000] Whites, 480,000 5 | Pleurisy............ 4,734,000 | 95“ 4,750,000 6 | Gastric cancer...... 2,579,000 | 51 2,550,000 7 | Syphilis........... 4,428,000 | 90“ 4,500,000 8 | Secondary anzmia. .| 2,632,000 | 52“ 2,600,000 9 | Pernicious anzemia. .| 1,178,000 | 24 “ 1,200,000 10 | Lymphemia....... 3,726,000 | 73 * 3,650,000] Whites, 102,400 11 | Normal............ 5,024,000 | 99“ 4,950,000 12 | Pernicious anemia. .| 2,907,000 | 59 “ —— | 2,950,000 18 | Normal............ 5,136,000 |102 “ 5,100,000 14 | Pernicious anemia. .| 2,934,000 | 59 =“ 2,950,000 15 | Debility(?)......... 4,784,000 | 96 “ 4,800,000 16 | Normal.... ....... 5,000,000 | 99 * 4,950,000 17 | Pernicious anemia. .| 1,596,000 | 32“ 1,600,000 18 | Debility (?)......... 4,584,000 | 92 “ 4,600,000 19 | Chlorosis...... ... 8,583,000 | 71“ 3,550,000 20 | Gastric cancer...... 4,080,000 | 81.“ 4,050,000 21 | Secondary anemia. .| 4,120,000 | 82 “ 4,100,000 22 | Normal............ 5,472,000 |109 “ 5,450,000 23 | Gastric cancer..,... 4,120,000 | 82“ 4,100,000 24 | Debility (?)........ 4,824,000 | 96“ 4,800,000 25 | Pernicious anemia. .| 1,976,000 | 40 “ 2,000,000 26 | Raynaud’s disease. .| 3,486,000 | 70“ 3,500,000 27 | Chlorosis........... 4,268,000 | 85“ 4,250,000 ‘Boston Med. and Surg. Jour., February 15th, 1900. CENTRIFUGALIZING THE BLOOD. 31 instrument was exactly correct in each case. In many of these cases I verified Dr. Scannell’s readings and counts. Dr. G. W. Fitz finds that the degree of dilution necessary to make the bright horizontal line appear corresponds with fifty-two corpus- cles to every thirty-six squares of the Thoma-Zeiss counter. This means that if a drop of the mixture be placed on the Thoma-Zeiss counting chamber, just after the bright line appears, fifty-two cor- puscles are to be found in thirty-six squares. If more or less are found the dilution has been proportionally incorrect. Tue Hamarocrit. The hematocrit of Hedin has undergone considerable modifica- tion and improvement and as remodelled and improved by Judson Daland has been used to some extent in this country. Its direct and obvious object is simply to ascertain the relative volume or mass of the corpuscles and of the plasma in a drop of blood; but the hope of its.advocates has usually been that it would supplant entirely or mostly the long, tedious, and eye-destroying process of counting with the Thoma-Zeiss instrument. To use the Daland hematocrit we prick the ear as usual and with the help of a bit of rubber tube attached to one end of the -eapillary tube (Fig. 14) suck in enough blood to fill it entirely. As soon as it is full, put the finger (greased with vaseline) tightly over the free end of the glass tube and then, but not till then, draw off the rubber tube and adjust the glass as quickly as possible in the place prepared for it on one of the horizontal arms of the whirling machine (Fig. 14). A similar tube (empty) should be put on the other arm of the crosspiece to make the balance true. The handle of the instrument is then revolved at least seventy times a minute for two minutes, at the end of which time (sometimes less) the column of blood cells is packed so tight that no further whirling has any effect on its length. To estimate the number of red corpuscles from the length of the column, we call each degree of the scale on the tube 100,000 cells, or a little more. Thus if the blood column in the tube ends at about the mark 50, we consider that the blood has rather more than 5,000,000 red corpuscles per cubic millimetre. So far all observers agree on the figures, but as to just how much more or less than 100,000 each degree on the scale is worth there is some variation 82 CLINICAL BLOOD EXAMINATION. between different observers. Daland' finds that the degree of the scale on the capillary tube corresponds to 99,390 corpuscles. So far as I can learn, the use of this instrument in Europe has been chiefly for the direct information it affords as to the volume of the red cells and the amount of re- spiratory surface in the blood, rather than for the indirect information it may give us as to the number of the red cells. It does not seem as yet to be supplanting the Thoma-Zeiss coun- ter. Its bulk and the noise it makes must for the present, I think, prevent its extensive use outside of hospitals. The noise it makes is a very loud and disagreeable one, and will deter many from using it in private practice. HemMoGuLopin EstTIMATION. 1. Tallqvist’s Hemoglobinometer. : 9 se “ Fig. 14.—Daland'’s Hematocrit. Two 2. Dare’s capillary tubes in place on the hori- 8. Oliver’s « zontal whirling beam. The instru- : 79 «“ ment is to be fastened to the edge 4. v. Fleischl s of some solid and bulky piece of Until recently the instrument most furniture by means of the thumb- s screw seen at the bottom of the cut. used both here and in Europe was that If not very tightly secured, it will of v. Fleischl. In France Hayem rules. work loose when the handle is re- volved rapidly. supreme in the matter of instruments, as in everything else concerning the blood, and in England Oliver’s apparatus is used to a certain ex- tent. Within a year, however, a contrivance originated by Tall- qvist’ has come into use and deserves, in my judgment, to sup- plant all others in clinical work. I shall therefore describe it first. LI. Tailqvist’s Heemoglobinometer. A drop of undiluted blood is soaked into a bit of filter paper of standard quality and compared (by ordinary reflected daylight) with a paper color-scale of ten tints, ranging from ten per cent to 1 University Med. Mag., November, 1891. 9 Tallqvist, St. Paul Med. Jour., May, 1900. HASMOGLOBIN ESTIMATION. 33: one hundred per cent. The scale was prepared by imitating in water color the tint of the blood of anemic patients (using the v. Fleisch] instrument) when soaked into the standard filter paper. The water-color standard colors were then reproduced in lithograph,. and the lithographed scale bound up with fifty sheets of the stand- ard filter paper makes an apparatus which can be easily slipped into- the pocket and carried to the bedside. In making the comparison the blood stain is put against a back- ground of white filter paper beside the color scale, and moved along until a match is found. The comparison should be made as soon as- the stain has lost its humid gloss, and before it is thoroughly dry. Artificial light cannot be used. Errors of ten per cent are possible, but it is my belief that far greater errors than this are frequently made with v. Fleischl’s or Oliver’s instrument in the hands of the: great majority of physicians. Tallqvist’s scale costs but $1.25, and can be used by any one with sufficient accuracy for practical. purposes, and with a celerity that makes hemoglobin estimation no: more of an undertaking than feeling the pulse. I have ‘used the instrument in several hundred cases, and have never yet been mis- led by it, nor found a greater error than ten per cent in comparison with Oliver’s instrument. IT. Dare’s' Hemoglobinometer. This excellent instrument is undoubtedly more accurate than Tallqvist’s, and would be preferable to all others but for its cost ($20), its bulk, and the time necessary to make an observation and to clean the parts. As in Tallqvist’s method, undiluted blood is used, and this con- stitutes an advantage over both v. Fleischl’s and Oliver’s instru ments. The blood is drawn by capillary attraction into the slit between two slabs of glass, one transparent, the other translucent and white, so as to diffuse the light used for illumination. The color of the blood is then compared with different portions of a circular dise of colored glass revolved by means of a thumb screw so that different tints are successively brought side by side with the blood tint. Transmitted light from a candle is used for illumination, and the observation is made through a telescoping camera tube excuding all extraneous light. As we turn the screw and bring different tints of the glass standard into comparison with 1 Phila. Med. Jour., October, 1900. 3 34 CLINICAL BLOOD EXAMINATION. the layer of undiluted blood, the percentage of hemoglobin can be read off from the etched scale which appears at a point opposite the color apperture. The sharply bevelled edge of the opening rests directly over the reading indicated. A pivoted black screen pro- tects the observer’s eyes from the direct light of the candle, and may occasionally be brought over the color apertures so as to rest the eye. The instrument is so made that blood film and standard color disc are viewed side by side in a horizontal plane through two cir- cular holes 5 mm. in diameter which are considerably magnified by a lens in the telescoping camera tube. In using the instrument we need no dark room—a great advan- tage. The instrument is simply pointed at some dark surface—a dark coat or corner. In order that the blood and the color disc should be equally lighted, it is essential to see that any curve that exists in the candle wick should point straight toward or away from the centre of the instrument in line with the juncture of the springs which support the candle. The reading should be completed before the blood film begins to shrink in from the edges, ¢.e., within ten minutes. The advantages of Dare’s instrument are: 1. Its accuracy; using undiluted blood and making allowance as it does for the color curve, it is, I believe, more accurate than any other clinically available instrument. 2. Leucocytosis does not disturb the reading (as it does in v. Fleischl’s instrument). 3. The errors and waste of time incident upon dilution are avoided since the instrument uses undiluted blood. 4, No dark room is needed. 5. It can be used and cleansed much more quickly than any other instrument except Tallqvist’s. My reason for preferring Tallqvist’s instrument despite these merits of Dare’s are: 1. Because accuracy greater than that obtainable with Tallqvist’s instrument, is seldom practically important. 2. Because an observation can be made with Tallqvist’s heemo- globinometer in about one one-tenth of the time needed for using any other instrument, 7.e., in about twenty-five seconds. 3. Because the Tallqvist instrument takes so little room and needs no cleaning or preparing for use. 4. Because it is so cheap. HZMOGLOBIN ESTIMATION. 35 IT. Oliver’ Hemoglobinometer. Oliver’s instrument corrects: two errors which are inherent in v. ‘Fleischl’s. ade 1. It has no sliding scale*of color, but compares the blood tint successively with definite tints of glass, each of which is even. The tints are worked out to cone pene to the specific dilution curve os blood, for: , Ho MA . Since every colored liquid changes color at a different rate a diluted, the dilution curve of blood does not correspond to that of glass (which behaves in this respect like a liquid). The glass wedge of v. Fleischl’s instrument represents a single color regularly diluted and does not correspond in its degrees to the colors of blood diluted at a similar rate. The scale of Dr. Oliver’s instrument is measured to correspond to the actual colors of the blood’s dilution curve, by means of the tintometer. In other respects the principle of the instrument is like v. Fleischl’s, and the method of using the two is practically the same except that in Oliver’s reflected light is used instead of transmitted light. Oliver’s instrument consists of a series of twelve tinted glass dises corresponding to the hemoglobin percentages from 10 to 120 and arranged in two rows (see Fig. 15, a). The intermediate degrees are measured by means of “riders” of colored glass, which can be laid on top of the primary color discs so as to deepen the tint seen. The capillary pipette (Fig. 15, 6) is somewhat stouter than v. Fleischl’s, but is used in the same way to collect the blood, which is then forced out of it with water from a medicine dropper (which is fitted with a rubber tube to slip over the blunt end of the pipette) (Fig. 15, c) and washed into a mixing cell (Fig. 15, d)-similar to v. Fleischl’s, except for the absence of a central partition. Hervé the blood is mixed in the usual way with water and the cell filled to the brim and covered with a small glass plate; a bubble always forms, but by turning the cell or moving the cover-glass we can usually get the troublesome shadow thrown by the bubble out of the color field. The blood thus prepared is brought close to the scale and there compared with the tint of the different standard color discs. If it matches one of them the observation is complete; if not we use one of the glass riders which enables us to read within two and a half degrees. A fuller set of riders 36 CLINICAL BLOOD EXAMINATION. can be obtained so as to make it possible to read down to one per cent. The standard is usually arranged for candle-light, but another set of discs can be obtained adjusted to daylight readings. The latter are less accurate. The same precautions as to the exclusion of outer light by means of a “hydroscope” tube, resting the eye fre- quently, etc., must be observed with this instrument as with v. Fleischl’s. [It can be obtained of J. H. Smith & Cie., Zurich Fig. 15.—Oliver’s Hemoglobinometer. a, Standard cclor discs; b, capillary pipette ; c, washing tube; d, mixing cell. (Wollishoften), for 115 francs plus duties and expressage, or of the Tintometer Company, 6 Farringdon Avenue, London, E. C.] The candle should be placed three or four inches from the instrument and arranged to light both the blood and the color discs alike. A word as to the use of the riders. The instrument as used for clinical work usually has two riders: the one having the deeper tint is used on the upper half of the scale, the other on the lower. Suppose we have decided that the blood color is between 60 and 70. Put the rider on the 60 disc and compare again. If the blood is darker than the 60 disc plus the rider, the percentage is approxi- mately 67} (since it is higher than 60+ 5 [the rider] and lower HEMOGLOBIN ESTIMATION. 37 than 70). If it just matches the 60 plus its rider, the reading is 65. If the blood is paler than this, yet darker than 60, it is about 62}. An error of about 2 degrees is obviously inevitable. IV. Use of v. Fleischl’s Hemometer. (a) Fill on one side of the metallic cell (a, Fig. 17) about one- quarter full of distilled-water. Put the end of the little pipette (B) horizontally into the side of the blood drop, which will at once fill nnnnnnhnnnnts B Fic. 16.—.A, Colored Fic. 17.—v. Fleischl’s Hemometer. a, Partition into which blood glass; B, capillary is put; a’, partition into which water is put; G. mixing cell; pipette. K, K, colored glass slip (see Fig. 16,4); P, P, metal frame on which scale is marked; R, S, reflector; T, screw which moves the frame, P, P. the tube by capillary attraction. Quickly wipe away any blood that may be on the outside of the pipette. Then put it into the water contained in one of the partitions of the metallic cell and rat- tle it quickly back and forth, so that the water may be forced in first at one end and then at the other. (6) After this the expulsion of the blood may be completed by forcing water from a medicine dropper through the capillary pipette and into the compartment where the mixing has been begun. Using the metal handle of the pipette, mix the blood and water in every part of the compartment. Then fill both compartments of the cell to the brim with distilled water, and adjust the compartment con- 38 CLINICAL BLOOD EXAMINATION. taining the clear water so that it comes over the slip of colored glass, while through the compartmefit containing the blood light thrown upward by the reflector below passes directly to the eye. »Turn the thumb screw (see Fig. 17, 7’) back and forth until the color of the glass is the same as that of the blood, and read off the L corresponds This gives the percentage of hemoglobin, 100 being the color of normal blood for men and 80-90 for women. (c) Matching the colors is not at all easy at best, but @ B may be somewhat aided by OO) 1. Do not stand (or sit) facing the light, but sideways C (z.e., at A or B, never at C, ee CO, wrong position for observer; D, cell compartments whose colors we are to match, on the right and left halves of the retina, which are equally sensitive in most . having a low hemoglobin percentage than for one nearer the normal. 3. Roll up a piece of paper ( preferably black) into a tube of such size that it will fit over the metallic cell (D, Fig. 18), and rest on 4. Use first one eye and then the other, and never look more than a few seconds at a time. 5. Move the thumb screw with short, quick turns rather than 6. If the preliminary reading shows one of thirty per cent or less, two or three pipettes full of blood should be used and the reading divided by 2 or 38. A considerable error can thus be number on the scale which observing the following pre- Fig. 18). By sitting as in persons. the platform of the instrument. Looking through this with one eye slowly and gradually, for sudden color changes affect the retina avoided. to that color. cautions : Fic. 18,—L, Light; .4 and B, right positions for Fig. 18, A or B, we get the 2. Use as little light as possible, and always less light for a blood we can judge the color more accurately. more than gradual ones. SPECIFIC GRAVITY. 39 Necessary Errors. A considerable error is absolutely necessary, inasmuch as the bit of colored glass to be seen at any one time through the aperture of the instrument is not (like the blood) all of one tint, but includes a variation of twenty per cent in color, i.e., if the glass appearing at one end of the aperture is opposite 50 on the scale, that seen at the other end of the aperture will either be at 30 or at 70. This difficulty is somewhat lessened by shutting off from view all but a small section of both compartments with a bit of black cardboard or metal in which a slit is cut asin Fig. 19. The slit is put at right angles to the partition which divides the cell so that ma. 19.—shield for Use the blood tint is seen at d and the glass tint at w. eee Many persons are not sensitive encugh to colors to attain any reasonable degree of accuracy with the instru- ment, and there is moreover a very considerable difference be- tween different instruments in respect to the color of the glass slip.’ All these difficulties render the instrument an unsatisfactory one in many ways. Its bulk and expense are also considerable and in my opinion its use should be entirely abandoned in favor of Tall- qvist’s or Dare’s instrument. EsTIMATING THE SPECIFIC GRAVITY OF THE BuLoop. The simplest and most available method for clinical use is that of Hammerschlag,’ a modification of Roy’s* method. Chloroform is heavier than blood; benzol is lighter. Mix ina urinometer glass such quantities of the two that the specific gravity taken by an or- dinary urinometer is about 1059, 7.e., that of normal blood. Punce- ture the ear, draw a drop of blood into the tube of a Thoma-Zeiss pipette, a small medicine dropper, or any other capillary tube, and blow it out again into the chloroform-benzol mixture. The blood does not mix at all with these liquids but floats like a red bead. If 1 Old instruments read lower than those recently manufactured. 2 Wien. klin. Wochenschrift, iii., 1018, 1890. 3 Proceedings of Physiological Society, 1884. 40 CLINICAL BLOOD EXAMINATION. it sinks to the bottom add chloroform, if it rises to the top add benzol, until finally the drop remains stationary in the body of the liquid, showing that its specific gravity is just that of the surround- ing mixture. Then take the specific gravity of the liquid, as we do of urine, and you have the specific gravity of the drop that floated in it. The following precautions are needed: 1. Have the inside of the urinometer glass perfectly dry and clean; otherwise the drop of blood may cling to it and flatten out against it. 2. It is usually well to have more than.one drop of blood in the glass in case any. mishap occurs with the first one. 3. Add the chloroform and benzol a few drops at a time, and after each addition stir the whole mixture thoroughly with a glass rod. 4. If we have reason to suppose the blood will be lighter than normal (i.¢., if the hemoglobin is probably low, vide supra), it saves time to start with a lighter mixture of chloroform and benzol. 5. Avoid having any air within the blood drop. This can gen- erally be seen either in the capillary tube or after the drop is in the mixture. It is safer to take the middle portion of the blood drawn into the capillary tube, as both the first and the last portions of the column are more apt to have air in them. 6. The whole process should be done as quickly as possible, else the chloroform or benzol may evaporate or work into the blood drop and so affect its weight. It is better to have a urinometer with a scale running as high as 1070, but this is not essential, for the clinically important spe- cific gravities are low, not high. The importance of the specific gravity of the blood, as hinted above, is not so much for itself, but because it runs parallel to the percentage of hemoglobin and gives a figure from which the latter can be computed. The specific gravity of the blood plasma varies very little (ex- cept in dropsy from any cause), and in the corpuscles themselves the variable element is the hemoglobin.' Consequently in most non-dropsical patients the specific gravity of the whole blood varies directly as the hemoglobin. The following exceptions to this rule must be borne in mind, 1Except in dropsy in which the corpuscles themselves may get water-soaked. SPECIFIC GRAVITY. 41 1. In leukemia the specific gravity is relatively higher than the hemoglobin on account of the weight of the leucocytes. 2. In pernicious anemia with high color index (see blow) the hemoglobin is about two per cent higher than we should gauge it to be judging by the specific gravity. To estimate the percentage of hemoglobin from the specific gravity, one of the following tables may be used, modified from Schmaltz, “Pathologie des Blutes,” etc., Leipsic, 1896, using a direct weighing method. Apparently a degree of specific gravity means much more at the top of the scale (7.e., 6.6 per cent) than at the bottom (13 per cent). This table has been verified by the re- search of Yarrow (University Med. Mag., 1899) through comparison with a standard solution of 13.77 gm. of prepared hemoglobin in normal salt solution (up to 100 gm.). It appears to be very ac- curate. Spec. Grav. Hemoglobin. Spec. Gray. Heemoglobin. 1080 = 20 percent. + 1049 = 60 percent. + 1085 = 30 eS * 1051, = 65 . 1088) = 35 % ° 1052 = 170 * i: 1041 = 40 * eS 1053.5 = 75 # se 1042.5 = 45 3 1056 = 80 “ 1045.5 = 50 = i 1057.5 = 90 fh fe 1048 = 55 1059 = 100 " . Srupy oF THE FINER STRUCTURES OF THE BLOOD. The study of dried and stained specimens with the help of the aniline dyes gives us much of interest and importance in regard to the blood. More can be told about a given case by the study of a dried and stained cover-glass specimen than by any other single method. Preparation of Cover-Glass Specimens. (a) Covers carefully cleaned and polished are arranged at the bedside in such position that we can quickly pick them up without touching their surfaces (see Fig. 1).*. The ear is punctured in the usual way, and one of the cover-glasses touched to the summit of the drop as soon as it emerges. This cover-glass is then let fall 1] often poise them on corks so that their corners are readily accessible to the fingers. The process of making blood films is far easier if another person prepares the drop for us so that we can stand ready with a cover-glass in each hand to catch the drop as soon as it emerges. 42 CLINICAL BLOOD EXAMINATION. upon another in such a way that their corners do not coincide (Fig. 20). If the covers are clean the drop spreads at once over their whole surface; as soon as it stops spreading, slide off the top one without lifting them apart, but exactly in the plane of their surfaces. Have a gas or alcohol flame at hand and dry instantly if you want to get the very best specimens; but this is not at all necessary for most clinical purposes. The under cover-glass is always better spread than the upper. The above method needs a good deal of practice. (b) An easier way of preparing blood films is as follows: Put a moderate sized drop of blood on a glass slide (not a cover- glass) near one end. Hold another slide.(or a cover-glass) against c So Slide | Bood dege Fig. 20. Fic. 21.—Spreading Blood on a Glass Slide. the first in the position shown in Fig. 21. Move the slide along in the direction shown by the arrow so as to spread the blood drop over the whole length of the glass as thinly as possible. The quicker the whole process is performed the better will be the re- sults. After drying the film in the air it can be fixed and stained as below described (ec) Howard and Pakes’ use the following modification of Man- son’s method: Bloodis collected on a bit of paper and with this is spread along the surface of a slide or of a large (14 in. by 3 in.) cover-glass. “We have tried various kinds of tissue paper and have finally accepted cigarette paper as the most convenient. There are two small points to be noticed. Firstly, the edge used must be the original machine-cut edge; and secondly, it must be that which is parallel to the ribs. The best papers are the Tarlene, or the Zig- zag, not the familiar A. G. papers. Strips are cut across the ribs so that each is about half an inch wide and as long as the original ! Journal of Tropical Medicine, February, 1899. SPECIFIC GRAVITY. 43 cigarette paper is wide. Should cigarette papers not be at hand, ordinary note paper may be used, but it is not nearly so good. “Tn making the film the strip is held between the thumb and first finger and is lowered till the under surface adjacent to the machine- cut edge just touches the drop of blood as it rests on the skin, and then by a slight lateral movement the drop is converted into a streak, la =| LTTE oe FIG. 22. as in the diagram. This end of the strip is at once laid blood down- ward on one end of the cover-slip, the other end being still held, and the blood having been allowed to spread out between the paper and the cover-slip, the paper is slowly drawn along the slip toward the other end. A fresh strip of paper should be used for each film ” Fixing the Films. These films have now to be fixed, either by heat or by half an hour’s immersion in absolute alcohol and ether (equal parts), or by the same mixture (30 c.c. each) plus five drops of a saturated alco- holic solution of corrosive sublimate (five minutes’? immersion), by chromic acid two per cent, or by exposure to the vapor of forty-five per cent formaldehyde. I have used all these methods, but found none of them to compare favorably with the method of heat fixation when we wish to study the leucocytes or the nuclei of any cell. ‘When we wish to see chiefly the changes in the red cells (as in studying the malarial organism, nucleated red corpuscles, degener- ative changes, etc.), the alcohol-and-ether method is good. But when, as in the majority of cases, it is the white cells in which our interest centres, the use of heat is very greatly to be preferred. Heat serves not simply to fix the cells on the glass and to prevent degenerative changes, but also to modify and greatly improve the staining power of the cell when Ehrlich’s triacid stain is used. The method of fixation by alcohol and ether needs little com- ment, the cover-glasses being simply left in the mixture half an hour or as much longer as is convenient. Half an hour is enough, 44 CLINICAL BLOOD EXAMINATION. In mest cases we use dry heat. The best way to do this is in a dry-heat sterilizer at a temperature of 115°-155° C., according to the size and construction of the oven and the kind of stain used. The temperature must be watched very closely, and as soon as it reaches the desired point the heat should be removed. Gradual heating and gradual cooling are best. If we cannot easily get access +o such an instrument, we can manage very well with any small iron or copper box having a door or lid and a hole for a cork which is perforated for the thermometer bulb. This supported over a gas or alcohol flame does very well. It needs about five minutes to get the temperature to 150° C., and as soon as it gets there the specimens should be taken out. The thermometer bulb must rest as near as possible to the blood films without actually touching them. Ovens vary a good deal in the amount of heat actually conveyed to the film with a given reading on the thermometer. Some heat the film as much with a reading of 115° C. as others with one of 150°C. The proper temperature must be ascertained once for all by experiment with each oven. The same end can be accomplished somewhat less accurately with a strip of copper supported over a Bunsen burner or a small gas or oil stove. The copper plate should be about a foot long and two or three inches wide. Such a plate supported on an iron tripod over a flame gets, after a few minutes, to have a fixed temperature at any given distance from the flame, the heat passing off at the end of the plate as fast as it comes, and so not accumu- lating. On this plate find the boiling point of water by dropping small drops of water on it, and put the cover-glasses at this point fuce downward. They may be left there for from fifteen minutes to as long as you please; but with the stain which I have used, fif- teen minutes’ heating gives as good results as a longer period, and excellent specimens can often be made with tive minutes’ heating.’ After allowing the specimens to cool they are ready for staining. A very fair oven can be made out of a five-ounce quinine can, by 1 With a little practice one can learn to make excellent specimens by sim- ply passing the cover-glass through a Bunsen or alcohol flame about twenty times very rapidly. The rate of speed must be learned by experiment, @.c., such a speed and such a number of exposures to the flame as turns out to give on staining a bright yellow color to the red corpuscles (never red or brown or gray), a good definition to the blue-stained nuclei and to the violet or pink granules of the polynuclear leucocytes. These are the essentials of a well- ‘stained specimen, and they depend (a) on the heating, (6) on the make of stain, ‘but only slightly on the length of staining (vide infra). STAINING. 45 boring small holes in opposite sides and drawing through them cop- per wires on which to support a piece of wire netting to serve asa shelf for the blood films. A circular hole punched in the top of the can admits a perforated cork through which a thermometer registering 200° C. is passed. The whole is heated by a Bunsen burner. STAINING. For all details of structure the Ehrlich tricolor mixture or one of the numerous modifications of it is most convenient. ‘The most use- ful and easily obtained of these is made by mixing: Saturated watery solution of orange G............... ee eee 6 c.c. ne “6 s “ acid fuchsin.................... 4" Saturated watery solution of methyl] green...........+000.. 6.6 c.c. Then add: GUY GETID i. svcca mies roid aiara crn Ween tanned Noa d ka aie eae NS acters C48 5 c.c. A DSOlUITE Whi Per cent g Age. § Red cells. ag Teane Remarks. 1 6 Bal ige-e naar 36,700 Nephritis acuta. April 30th. 27,300 May 7th. 34,400 May 14th, otitis only. 27,000 May 22d. 21,000 .. |May 28th, slight discharge still. 2 2 Mi) gas cees 2 23,000 55 3) 19 ball ane Saat 21,900 .. |Ninth, T. 103.6°. 18,200 Eleventh, T. 101°. 10,800 4 Fourteenth, T. 99°. 4 6 MG eta aaa 18,600 20 5) 20 Lill Aeneas 17,000 .. |With jugular thrombosis. 21,900 Third day. 6) 46 Mi) prieeee a 14,500 With cerebral abscess. 7| Adult. | M.| 4,786,000} 16,800 .. |Serous. 8} 47 F. | 4,168,000] 16,600 65 |Double purulent; vent not free ; mastoid sore. 9) 19 F. | 5,120,000] 16,480 88 |April 28th. 8,800 49 May 5th, well. TO) 2M 4 Sill doeear tab acs 15,800 11) Adult. | F. | 5,942,000} 15,200 .. |Pus. 12 F. | 4,472,000] 14,750 60 December 7th, hysteria. 5,416,000; 9,750 46 |December 25th (during dyspneic and cyanotic attack). 13 9 dpe |acaksesaane 18,900 14) 32 aiet|| dasa ehaeaea 12,000 = Serous. 15 24 .. | 4,472,000] 11,200 20 Serous. 16 22 Ge || higher ars 11,000 17) 27 F. | 4,850,000) 8,500 69 —_|Serous. 18 7 F. | 4,416,000} 6,400 .. |Catarrhal. 19) Adult. | F.| 4,100,000} 4,000 Serous. 20 4 |M.|........ Marked Purulent; chronic right, acute leuco- left. Diff. 116 cells ; polymor- cy tosis. phonuclear cells, 57¢ ; lympho- cytes, 81; eosinophiles, 3. In some cases the blood alone enables us to distinguish otitis In a case recently examined which and its effects from typhoid. OSTEOMYELITIS. 251 several excellent clinicians pronounced typhoid, though there was a marked leucocytosis and no serum reaction, the autopsy showed pus in the jugular and lateral sinus but no typhoid. OSTEOMYELITIS. In four cases in which no external opening was present, the patient complaining only of pain in the bone, the counts of leuco- cytes were 29,600, 25,600, 24,310, and 18,000; in each the predic- tion that pus would be found was verified at operation. Three differential counts in chronic cases with sinuses showed nothing re- markable, no increase of eosinophiles and no myelocytes. The diagnostic value of the blood in osteomyelitis seems to me considerable, inasmfich as it is difficult by the symptoms alone to feel sure enough of the existence of pus to be willing to operate. “Rheumatic pains,” “growing pains,” and neuralgia can be ex- cluded by the presence of leucocytosis. OTHER ABSCESSES. (1) Felon.—It is striking to see how small a collection of pus can raise the leucocyte count. Patients with felons containing less than one-half drachm of pus may have a leucocytosis of 15,000 to 22,000. Ihave counted the blood in three such cases. The element of septicemia must be considerable. It seems to make no difference whether or not the pus is under great tension. The leucocyte count does not fall sharply after the felon is opened, but gradually dimin- ishes during the next seven to ten days. Even a (2) Gum boil raised the white cells to 27,000 in one case. An (3) Abscess of the vulva showed 23,500 leucocytes per cubic mil- limetre, and an (4) Abscess of the vagina, 12,800. Other varieties are: (5) Parotid abscess, 45,500 leucocytes per cubic millimetre. (6) Subpectoral abscess, 16,000 leucocytes per cubic millimetre. (7) Abscess of the neck, 22,200 leucocytes per cubic millimetre. Carbuncle, 41,000 leucocytes per cubic millimetre. (8) Psoas abscess (infected), 50,000 leucocytes per cubic milli- metre. (9) Abscess of ovary, 26,000 leucocytes per cubic millimetre. (10) One case of perinephritic abscess was watched for some days while the patient was getting up strength for an operation. It was 252 SPECIAL PATHOLOGY OF THE BLOOD. an abscess of several months’ standing, not increasing in size during the last month, and the counts, as we should expect, did not rise or fall considerably but showed a steady well-marked leucocytosis. July 29th, white cells, 21,400 “ “30th, “21,200 August 8th, “ “22,400 “« (1th, “ “ 23,000 “ 24th, “ “ 22,200. (Operation. ) A second case counted showed only 16,000. Both abscesses con- tained over a quart of pus. A third case, evidently tuberculous in origin and probably not much infected with pyogenic cocci, showed only 10,000 white cells per cubic millimetre. . (11) Abscess of the Lung.—Five cases following pneumonia have occurred at the Massachusetts General Hospital within the last three years; the counts were as follows: Case I., 16,800; Case IL., 16,000; Case IIT., 16,400; Case IV., 30,000; Case V., 5,100. (12) Subphrenie abscess, four cases. Case. | Red cells. | White cells. i nie. Remarks. 1 | 4,450,000) 58,267 Bo | reeves acs 25,600 | .......... May 16th. 10,500) }csineesanes May 17th. 17, 600 55 May 20th. 3 | 8,200,000] 22,000 38 Be) | toes ea 15,300. | sscesace ces October 20th. Supposed typhoid for first week. 18,800 | .......... October 22d. 16,600 | csessesees October 27th. 18,000 | secs. esees November 5th. RR DO0 || sciqutcs be dons November 10th. Operation; a quart of pus; recovery. Diagnostic Value. 1. The patient with vulvar abscess was so morbidly modest that she complained of all parts of her body except the one diseased, and gave a train of symptoms which failed to account for the leucocy- tosis. The presence of this leucocytosis called for a much more searching physical examination than would have otherwise been made, and the seat of real trouble was discovered. 2. (a) The diagnosis between perinephritic abscess and cyst of YELLOW FEVER. 253. the kidney is materially assisted by the fact that the former causes leucocytosis, while the latter (see page 335) does not. (6) Both cancer of the kidney and perinephritic abscess cause leucocytosis, but if fibrin is not increased cancer is the more likely of thetwo. This differential mark has served me well in two cases. (ec) Hydatid of the kidney and pyonephrosis are not to be dis- tinguished from perinephritic abscess by the blood examination. In abscess of the lung the blood gives no information that cannot be more easily gained in other ways. 3. Subphrenic abscess may be confounded with malignant dis- ease, both of which may cause leucocytosis; but the absence of any increase of fibrin speaks against the existence of an abscess. GONORRH@A. The red cells are not affected, but in acute cases a moderate leu- cocytosis is present and fibrin isincreased. Qualitatively, the white cells have been said by Neusser and others to show an increased percentage of eosinophiles corresponding to the large proportion of these cells in the urethral discharge. Vorbach has carefully studied twenty cases with reference to this point and finds the eosinophiles in the blood to vary from 0.5 to 11.5 per cent—averaging 4.2 per cent—within normal limits. Bettman found the eosinophiles usu- ally increased, especially when the posterior urethra was involved. In one case with epididymitis the eosinophiles numbered 25 per cent.’ YELLOW FEVER. Jones’ found coagulation slow, the red cells not much dimin- ished but showing decided degenerative changes; hemoglobinemia. is common. He makes no observations as to the white corpuscles. Pothier of New Orleans, studying the epidemic of 1897, found the following results in 154 cases. The red cells were never consider- ably diminished. The leucocytes varied from 4,600 to 20,000— averaging about 9,000—hemoglobin usually diminished at the height of the disease 50 to 75 per cent. Normoblasts were noted in a few specimens. A case recently observed at the Massachusetts General Hospital showed two days before death 7,800 leucocytes, 92 per cent of heemo- 1 Archives for Derm. and Syphil., vol. 49. ? Journal of the American Medical Association, March 16th, 1895. 254 SPECIAL PATHOLOGY OF THE BLOOD. globin, with an absence of the typhoid serum reaction. Through the kindness of Dr. Pothier I have been able to study cover slips from twelve cases of yellow fever from the Charity Hospital of New Orleans. The differential counts of leucocytes are as follows: I. | IL. | U1 | IV.| V. | VI.) VIL. | VII.| IX.) X. | XL.) XI. Polymorphonuclear neutro- chnes aisisibjace a oyansate date auameatare ars v7 | 74 | 93 | 86 | 87 | 88 | 97 84 | 86 | 84) 77 | 73 Small lymphocytes... .. ay 18 | 22 | 15 | 11 E 4 3 5 4 : 4 * 4 Large lymphocytes “| 5 2/ 2] 2 8) 4s 11 | 10 Eosinophiles ...... sent eed a a + ive eg 1 1 Myelocytes ee Red cells showed nothing except in Case VIII., in which there were marked deformities and a few normoblasts. In some cases there was a marked leucocytosis, in others none. (For serum reac- tions, see page 458). TYPHUS FEVER. Ewing' in four cases found no leucocytosis. Tumas’ found no leucocytosis, as the following case shows: Temperature. pee eee Red cells. fgecorionin, White cells. aM, P.M. 4th. |...... 40.0 5th. | 89.2 | 39.6 | 4,440,000 80 9,600 6th. | 39.0 | 39.5 | 4,220,000 V7 4,800 7th. | 39.0 | 40.0 8th. | 39.2 | 39.3 | 4,280,000 a7 3, 200 9th. | 39.0 | 89.5 10th. | 38.8 | 89.2 | 4,440,000 vid 8,200 11th. | 38 3 | 89.3 12th. | 39.0 | 39.2 | 4,880,000 80 1.600 18th. | 38.8 | 89.5 | 4,780,000 80 3,200 14th. | 38.7 | 39.0 15th. | 88.0 | 38.7 | 4,960,000 80 1,600 16th. | 88.1 | 38.8 17th. | 38.7 | 38.6 | 4,160,000 70 4,800 18th. | 37 7 | 88.2 19th. | 86.6 | 88.5 | 8,820,000 67 1,600 20th. | 88.1 | 38.38 21st. | 87.5 | 38.1 | 3,450,000 62 38, 280 | 22d. | 88.1 | 87.8 | 8,450,000 60 8,200 83d. | 87.5 | 88.0 24th. | 87.4 | 88.0 | 8,130.000 50 8,200 25th. | 87 4 | 39.3 26th. | 89.2 |...... Died on the 26th. 'Ewing: New York Medical Journal, December 16th, 1898. * Arch. f. klin. Med., vol. xli., p. 368. THE BUBONIC PLAGUE. 255 On the other hand, Everard and Demoor,' and Wilks’ found leucocytosis. MALTA FEVER. According to the article in Allbutt’s recent “Text-book of Med- icine ” the red cells fall gradually in the course of the fever from 5,000,000 to about 3,500,000. Bruce finds the leucocytes normal in most cases. (See also page 466.) Charles’ makes the amazing assertion that at the height of the fever polymorphonuclear neutro- philes are entirely absent from the blood and only lymphocytes to be found. Musser and Sailer report a prolonged case with no im- fFortant changes in the blood. The serum reaction with the Bacillus melitensis has been obtained in cases of Malta fever by Musser, by Cox, by Curry (18 cases), and in Osler’s clinic. GLANDERS. Christol and Kiener* reported leucocytosis in glanders. In a fatal ease of acute glanders with autopsy which was recently studied at the Massachusetts General Hospital the following counts were re- corded : October 24th, 1897. Leucocytes, 18,600; hemoglobin, 100 per cent. October 81st, 1897. Leucocytes, 11,600. November 4th, 1897. Leucocytes, 18,000. November 9th, 1897. Leucocytes, 12,600. November 12th, 1897. Leucocytes, 12,400. Serum reaction absent; fibrin increased; pure culture of glanders bacilli from abscesses; 86 per cent of the leucocytes were polymorphonuclear; eosino- philes absent. The bacilli of glanders can occasionally be cultivated from the blood. THE BUBONIC PLAGUE. In 1895 Aoyoma, a Japanese observer, studied the blood of this disease.° He found the bacilli peculiar to the disease by cover-slip 1 Annales de l'Institut Pasteur, February, 1893. 2 Ref. in Sajous’ Annual, 1895. 2 Lancet, July 30th, 1898. 4 Comptes Rendus de 1’Acad. des Sciences, November 23d, 1868. 5“ Mittheilungen aus d. Med. Fac. d. Kaiserlich Japanischen Universitit,” vol, iii., No. 2. Tokyo, Japan, 1895, . 256 SPECIAL PATHOLOGY OF THE BLOOD. preparations from the blood. The red corpuscles were not altered except that their number per cubic millimetre was at times increased (e.g., 7,600,000, 8,190,000). The cause of this I do not know, but it accounts for part of the leucocytosis. The white corpuscles showed a marked increase— 20,000 to 200,000 (!) per cubic millimetre. This leucocytosis was made up almost wholly of polymorphonuclear leucocytes ; the eosinophiles were markedly diminished, and the blood plates were increased. The Austrian Plague Commission found only a moderate leucocytosis in most cases. ACTINOMYCOSIS. Ewing (Joc. cit.) reports leucocytosis (21,500) in a single case affecting the lungs, and Schmidt gives the following: Date. Red cells. White cells. HoRnOnonI October. Gthi: ssagaceavs ocsaseaiewes| sander de 12,000 "35 LE CH. cs sieusiatans S ccateuaare Recaverene 3,170,000 14,500 * OG resi vactobeuarratets 0.8. Rie iecaueeeGereetl| ub deen aiaes 19,700 s 26th. sc Ge masiewen aa veda wenn 8,200,000 22,900 38 November 4th................02 005 2,550, 000 18,900 23 In two cases of actinomycosis occurring at the Massachusetts Gen- eral Hospital the following counts were recorded : Case. Location of the disease.| Leucocytes. Remarks. L pacaas dates: Liver widens 2344 31,700 June 18th, 1897, 28,400 “19th. 28, 200 “ 25th. Autopsy. Qi cand aeaieanins LUNGS: piasccaccds 20,900 April, 1897. 23,000 August, 1899. Autopsy. EPIDEMIC DROPSY. (Acute Anzmic Dropsy. ) MacLeod, in Vol. IIT. of Allbutt’s “System of Medicine,” de- scribes under this title a disease not uncommon in India and other tropical countries. The blood shows a marked and constant anemia with leucocytosis and an “increase of granular or molecular matter in the serum.” Dr. Green, of the United States Marine Hospital service, recently wrote me an account of two cases strongly resem- RELAPSING FEVER. 257 bling MacLeod’s description of epidemic dropsy; these cases were. observed by Dr. Greene at Key West, Fla. One was fatal and the other ended in recovery. The blood of both cases was notable in that the corpuscles were almost invariably oval instead of round, re- minding him of the blood of amphibia. He was good enough to Fic. 33.—Blood in Epidemic Dropsy. Note oval shape of corpuscles. Magnified 350 diameters. send me preparations of the blood; a microphotograph of one of them is here reproduced. Rouleaux formation was absent, another point in common with amphibian blood. There was no apparent in- crease of the leucocytes when I saw the blood, late in the conva- lescence of the second case. (On the significance of oval forms, see p. 85.) TETANUS. In two (fatal) cases of tetanus treated with antitoxin, I observed the following counts: White cells. Hemoglobin. Case J. June 2ist, 1897............ 0.000 eee 11,100 70 per cent. June 28d, 1897.0... cece cece cence 11,900 SOD | asteaa wh, Sess wlartiagunuia aaa ge eu 19,600 The eosinophiles do not decrease as in most fevers. 17 258 SPECIAL PATHOLOGY OF THE BLOOD. BERI-BERI. In a single afebrile case seen at the Massachusetts General ‘Hospital the following is recorded: Red cells, 3,896,000; white ‘cells, 7,800; hemoglobin, 48 per cent. The eosinophiles are said to be much increased in the acute stages. Spencer' states there is no leucocytosis. Ewing and Daubler, each in 3 cases, found normal leucocyte counts with moderate ane- mia and no eosinophilia. RELAPSING FEVER. (See page 422.) (a) Diagnosis. Leucocytosis is the rule. It is most marked just after the crisis. In countries where this disease is common the difficulty in diagnosing cases between attacks (when the spiro- cheetes are absent from the blood) is frequently met with. Lowen- thal has perfected a method by which in most cases the diagno- sis can be made by means of the effect of the serum of suspected cases on the spirochetes of other active cases. The organism cannot be cultivated as yet, so that a diagnosis of this kind is pos- sible only during epidemics when fresh blood containing the organ- ism can be obtained. A drop of blood from the suspected case is mixed with a drop from a patient then undergoing a paroxysm, and the two are sealed with wax between slide and cover-glass and left in the thermostat for half an hour together with a mix- ture of normal blood and blood containing spirochetes as a con- trol. At the end of that time, if the case be one of relapsing fever, the organisms in contact with the blood from that case cease their motion, while those in the control are lively. It is not a clump re- action but a direct bactericidal effect which persists in the serum nearly up to the time of the next attack. The diagnosis so made by Lowenthal in forty cases was verified in every case by the course of the disease. In this way mild or abortive cases with few organisms in the blood can also be identified. (b) Prognosis. If the above bactericidal power lasts as late as ‘the seventh day from the last attack, and in sufficient intensity to immobilize the spirochetes in one hour or less, there will be no re- lapse. If these conditions are not fulfilled, relapse is sure to fol- low unless prevented by treatment. Lowenthal has verified this prognostic use of the serum in over one hundred cases. 1 Lancet, January 2d, 1897. CHAPTER V. DISEASES AFFECTING THE SEROUS MEMBRANES. TusBERcuLous affections of serous membranes have been dealt with elsewhere (p. 280); but an exception was there made of pleu- risy, for although there is reason to believe that the majority of cases of serous pleurisy are due to tuberculosis, we rarely have proof of it, and most observations upon the blood of pleurisy have not been accompanied by bacteriological examination of the effusion. Tu- berculous cases have not always been distinguished from non-tuber- culous. Hence the two are necessarily considered together here. SEROUS PLEURISY. Von Limbeck finds in non-tuberculous cases from 13,000 to 15,000 leucocytes per cubic millimetre. The red cells and hemoglobin are not much affected except in chronic cases. Rieder finds in non-tuberculous cases during the stage of fever moderate leucocytosis, 13,000 in one case in which the bacteriolog- ical examination showed the presence of Fraenkel’s diplococcus in the exudation. After the fever has subsided the leucocytosis falls to, or nearly to, normal, so that cases examined for the first time some weeks after onset would show no increase at all. This he thinks explains the results of Halla and others who found no leuco- cytosis in serous pleurisy. According to Rieder the presence or ab- sence of leucocytosis depends not so much on whether the product is serum or pus as on whether the trouble is stationary or ‘advancing. In tuberculous pleurisy despite fever Rieder found but 4,600 white cells in one case, and Pick got similar results in two cases. Hayem makes no clear distinction of tuberculous and non-tuber- culous cases, and states that “acute inflammatory ” pleurisy has from 7,500 to 12,000 leucocytes per cubic millimetre. The fibrin network is much less dense than in pneumonia; in most of the tuberculous cases it is not increased at all. Morse reports 224 counts in 20 cases of serous pleurisy—9 of 260 SPECIAL PATHOLOGY OF THE BLOOD. them tuberculous. No relation could be established between the number of leucocytes and the presence, absence, or degree of fever, the presence of blood or microscopic pus in the fluid, the amount of fluid or the duration of the illness. Increase or decrease in the amount of fluid was not accompanied by any parallel change in the circulating leucocytes. Only 10 of the 224 counts were over 11,000, and 9 of these 10 were in a single case which was shown at autopsy to be complicated by a secondary pneumococcus infection. Morse concludes that primary serous pleurisy does not show a leucocytosis. His figures are as follows: From 3,000 to 4,000.............. 2 cases. fe 4,000 “ 5,000.............. 19 “* ‘ 5,000 “ 6,000.... .......0. 40 “ : 6,000 “ 7,000 ...........06. 31 “a 7,000 “ 8,000.............. 50. = 8,000 “ 9,000...........00. 42 “ 9,000 “ 10,000 .............. 27 “10,000 “ 11,000 .............. 8. = “11,000 “ 12,000.............. 4 “18,000 “ 14,000..........0.0.. j= MAOUAL dice -tvashs Sa reeay obec Sees 224 cases. The following chart (Morse) shows how “ the white count dodges up and down without the slightest apparent connection with the quan- tity of fluid.” In 242 cases examined at the Massachusetts General Hospital the count of leucocytes was: TaBLE XXIV.—PLeEvnRitic Errusron (SERovs). Between 3,000and 4,000 ...................0., 4 cases. € 4,000 “9,000. 2 encase scseavedioae ce Ty. -c8t « 5,000 “ 6,000 ..................000. 30 sf C2000" - TO00 ts oz sack ade oa Gaeaitieeceencny 29 fe (000 8 8000 occu ic gud pe oa sao: 26 ee S000 “9000 iit ar aneeeeeectcns nou, 40 “ se 9,000 “103000 cece cccbaeoa ce ace mace 29) e 10,000 “ 11,000.......00 0... ee eee 27 = LT O00:. T2000 ics icd-oes utters ose uid 11 “ : 12000. 155000 5 sc% cae ae Ab eae bs een 25 ONT 15,000 ss ge cols we ctv ae SANE Solon.be oleae ck 10 “ LOLA) ccna hahaa aa bared pon ban oeawnleeles 242 cases. Average = 6,130. SEROUS PLEURISY. 261 Here tuberculous and non-tuberculous cases are not distinguished, and a majority of them were not seen till the trouble had been going on two or three weeks. The patients did not seek advice until the effusion was large enough to cause dyspnoea. Of the 242 cases all but 35 had no leu- cocytosis. Most of the cases were afebrile or nearly so. Eight cases reacted to injections of tuberculin. None of these eight had leu- cocytosis. The cases with leu- cocytosis were mostly those seen in the fe- brile stage, near the beginning of the sick- ness. No differential counts were made. In chronic cases the red cells are said to be considerably di- minished, but this has not been the case in Fie. 34. our series: no count of under 4,000,000 was recorded, and the coloring matter was not much diminished. 14 Summary. 1. Red cells and hemoglobin show no important changes. 2. In adults the white cells are probably never steadily increased as a result of simple uncomplicated serous pleurisy. Occasional waves of leucocytosis occur in a small percentage of cases, but even then the leucocyte count rarely reaches 14,000. Continuous leuco- eytosis indicates some complication. Diagnostic Value. The blood count may help a good deal in doubtful cases by ex- cluding empyema, pneumonia, and malignant disease of the lung, all of which are accompanied by high leucocyte counts. Compare the average count in serous pleurisy, 6,130, with the average in pneu- 262 SPECIAL PATHOLOGY OF THE BLOOD. monia, 24,000, or in empyema, 18,300. The few counts I have seen of malignant disease of the lung have been still higher. Hayem insists, rightly it seems to me, that clinicians could get real help from blood examination in almost every case of doubtful diagnosis in which the lung and pleura are in question. In children the leucocytes are sometimes considerably increased by even a serous inflammation, their blood reacting always more strongly than that of adults to any morbid influence, and in them it may be impossible to distinguish serous from purulent pleurisy. PURULENT PLEURISY (EMPYEMA). The counts in twenty-six cases observed at the Massachusetts Hospital are as follows: TABLE XXV.—EMPYEMA. rr Per cent o | AGe.| Sex.| Red cells. White haemo- Remarks. s cells. | globin. ee TR lata ih ie ceseiun torte 57,800 54,400 2 2: ais | hawetae 55,000 aft Streptococcus. 5,440,000 | 49,200 51 BO | Fo eee sees 45,500 cs Pneumococci in pus. 37,700 31,700 4) 2] .. | 3,082,000 | 45,000 35 34,000 .. {Fifth day. 40,000 .. |Eighth day. 5 AN ro ll ct dee heats 44,000 te First day. 24,400 .. |Third day. 23,000 .. {Fifth day. 20,000 .. |Eighth day. Tap. 24,000 - Eleventh day. 31,400 .. |Fourteenth day. 22,000 .. |Seventeenth day. 41,500 60 G20") a5. | wa meres 41,000 .. |February 11th. Tap. 29,900 ee February 15th. Tap. Ped | seek lll iastilenateadeaaes 38,000 Bo SONG keel aaeeuatasee 2 37,800 9182) ce | ace nates 35,600 35,200 105) Av)! cm 1) seshaeraes 34,500 6,000,000 | 32,000 Te | epee | wacaceann 30,400 DQ AR aus | se atbparcunies 3 30,000 .. {First day. 39,000 .. |Third day. 27,000 .. |Sixth day. 26,000 .. |Eighth day. Pneumococci in pus. 190) 88] a. |) aarcage ss 30,000 PURULENT PLEURISY (EMPYEMA). 263 TARLE XXV.—EMPYEMA (Continued). i Per cent ‘ White a s Age.| Sex.| Red ssi calls. eienth Remarks. 14-2601), 24°) aaacagas 24,000 21,000 22,800 45 22,800 Ge June 5th. 34,700 June 7th. 29,800 June 8th. Tapped turbid serum. 17,700 June 9th. 22,000 June 10th. 22,100 June 12th. 21,800 June 14th. 17,200 June 22d. 27,300 June 24th. 80, 100 June 29th. 25,800 July 8th. 22,600 Pneumococcus. 153) <6 as. | ae watcen 21.600 Pneumococcus. 34,500 Five days later. 20,600 January 5th. 14,700 January 7th. 11,400 January 23d. 11,700 January 26th. Tapped. 18,000 January 30th. Re-accumulation. 26,000 February 8d. Operated ; pneu- mococci and streptococci. TGs) 2 | oe daar 19,600 17 | 45 18,700 Friedlinder’s bacillus. 18 | 6 16,900 ae Tap, pus. 19 | 24 4,152,000 | 15,000 45 |Operated. 208 BT | a, [sue dsc wie 14,200 QT BO os ll Ga aeweacenane 13,300 Gangrene of lung also. 14,900 Fifth day. 22,800 Fifteenth day. 22.130 | se | wiweee 13,000 200 SB bis? ll aweewmalae 18,000 Sterile. 24.) 22.) «e-|) sawaga-s< 12,700 o¢ Tuberculous. 4,192,000 | 10,800 48 |December 20th. 18,500 .. |December 22d. Broke into lung; cultures sterile. 14,500 January 2d. 18,300 January 4th. 10,000 ee January 9th. 16,200 50 Pneumococcus. 15,500 15,200 4,500,000 | 14,000 4,850,000 | 12,650 85 12,450 60 4,000,000 | 12,000 11,700 44 |Cultures sterile. 10,900 2D ed: | Sea || woauttenacd 8,400 Three quarts sterile pus. 7,600 Operated; several pints of pus; 26 | 45] .. | .....ee 6,500 streptococci. 264 SPECIAL PATHOLOGY OF THE BLOOD. This is in marked contrast with serous pleurisy as above noted. Von Limbeck noticed the same thing. (Ewing:) “In a case of empyema, in which tubercle bacilli were extremely numerous, the writer found moderate intermittent leu- cocytosis (maximum 18,000).” PERITONITIS. A patient with serous pleurisy (non-tuberculous) is hardly ever in danger, while if the general peritoneal cavity is the seat of a like inflammation, recovery is almost out of the question. This clinical difference is parallel to the difference in the blood condition. Any inflammation of the peritoneum (non-tuberculous), whether serous or purulent, calls very large numbers of leucocytes into the peripheral blood. The only exceptions to this rule are those cases in which the organism is: so overwhelmed by the dis- ease that it offers no resistance. We have seen that this same effect is produced in the severest cases of pneumonia and diphtheria, and presumably it is true of many other infectious diseases in which the blood has been less carefully studied. Almost all cases of general septic peritonitis show very marked leucocytosis, and the spreading of a localized process is always in- dicated by an increasing leucocytosis. But here and there it hap- pens that the patient cannot react against the disease at all, and then the leucocytes are normal or diminished. This never occurs in empyema, because the system is never so overwhelmed by a sep- tic process in the pleura. The fibrin network is increased in almost all cases. The following counts, all in fatal cases, illustrate these points : TABLE XXVI.—GENERAL PERITONITIS. White | Per cent No.| Age. | Sex. | Red cells. cells. hemo: Remarks. globin. 1 34 F. 4,860,000 54,000 | ...... Abscess of spleen (?). 2) Adult.| F. 7,000,000 Oe QUO) I ac seek Purulent ; from appendix—myelocytes, 2 per cent. 3 15 ee | chageeess 28,000) | aa sauce General septic. 23,000 | ...... Next day. 4 27 ae || -raendee 27,800 68 December 6th. Epigastric. 23,000 | ...... December 11th. 4,004,000 34,200 53 December 17th. Bi 2B OW awe eevee 24,100 ...... |Pelvic, after abortion. Seventh. 17,800 Fifteenth. 6 aT M. 5,317,000 24,000 Dysentery, with perforation. 7 OD aie |W aecaace sine 28,200 Gast ulcer; perforation; operation. eath. PERICARDITIS WITH EFFUSION. 265 TaBLE XXVI.—GENERAL PERITONITIS (Continued). No.| Age. | Sex. | Red cells. ae eg Remarks. globin. 8 | Adult.| F. 4,000,000 22,000 | ...... Chronic, purulent. 9 31 Ms |) Sanisasstcis 19,000 | ...... Ruptured bladder. 10 | Adult.| M. |] ........ 16,000 | ...... Moribund. aol Qo | | wees see 13,000 | ...... First day. Rupture of gall bladder. 25,800 | oo... Second day. Died. 12 21 Ms |l aici cies 12;200) | cesses June 30th. 9,000 | ...... July 2d. Autopsy. 13 32 gen teed tee 11,000 | ...... October 27th. Circumscribed. 8,300 | wo... November 2d. 14 26 a Th, aiwidy eas TA00 | sscmaiene July 19th. 95700) |) naacion July 28th. 15 | ce || geyapees 6,000 16 | Adult. | M. 6,000,000 6,000 | ...... Purulent; operation. Death. 17 52 F eee DjB28 | vec Obstruction; died in three days; au- topsy. 18 | Adult.| M. 5,760,000 5,800 | oo... Purulent. Death within 24 hours. 19 41 EB, 6,840,000 4,600 95 o on Soe 20 aon ta ||) & deere Marked | ...... After appendix operation. Diff. 1,000 increase. cells: Polymorphonuclear cells, 90.5 per cent; lymphocytes, 9.5; eosino- philes, 0; myelocytes, 1. 21 38 Be) sascavey 1,700! August 2d. Autopsy. 2,100! August 3d. 22 2 | ll) Cae seat scien 600 General. Gastric ulcer. Diagnostic Value. 1. When a diagnosis rests between peritonitis and (a) obstruc- tion (non-malignant); (7) malignant disease; (¢) hysteria, phan- tom tumors or malingering, the presence of marked leucocytosis with. increase of the fibrin network speaks strongly in favor of peritonitis. Obstruction or malignant disease may increase the number of leucocytes, but rarely increases the amount of fibrin. Hysterical or malingering patients have normal blood. 2. We cannot distinguish serous from purulent peritonitis in septic cases, but tuberculous peritonitis can always be excluded if leu- cocytosis is present. 3. As to the “chronic granular peritonitis,” non-tuberculous and non-septic, I have seen no reference in hematological literature and have no first-hand knowledge. 4. In the worst cases leucocytosis may be absent, as in the most virulent type of pneumonia. PERICARDITIS (WITH EFFUSION). As in most other inflammations of serous membranes we can dis- tinguish the tuberculous cases which have no leucocytosis from the rheumatic or septic cases which always increase the white cells. 266 SPECIAL PATHOLOGY OF THE BLOOD. The tuberculous cases are discussed under tuberculosis (see p. 285). The following counts illustrate the rheumatic form of the disease: TABLE XXVII. Fer cent Case.| Red cells. | White cells.| hamo- Remarks, globin. Pi wetrerts 42,400 | ...... November 3d, 1895. 32,600 | ...... November ‘th, 1895. 19,200 | ...... November 11th, 1895. 17,500 | ...... December 8th, effusion nearly gone.. 2 2,632, 000 21,600 45 December 24th, endo - pericarditis, chronic nephritis. 27,100 | ...... December 26th. 36,600 | ...... December 29th, no fever. 26,700 | ...... May Ist. 19,200 | ...... May 3d. 24,800 | ...... May 4th. 28,600 | ...... May 7th. 20,100 | ...... May 8th. 8 | 4,568,000 | 26,000 67 |December 14th. ie 19,400 | 1.0... December 20th, effusion subsiding. 4 | eaten 24, 000 5 | 4,168,000 | 19,447 67 Gi |) seveeene 15, 400 hoa Sains 14, 600 65 |Autopsy. BON Parties 12,000 63 |Tapped. Hayem has noted that pericarditis is far more apt to produce leucocytosis than is endocarditis. Diagnostic Value. In excluding cardiac hypertrophy or simple dilatation with rup- tured compensation, both of which may occasionally simulate a pericardial effusion, the presence of marked leucocytosis is abso- lutely decisive. When we are sure that effusion exists, the absence of leucocytosis points strongly to a tuberculous process as its cause. MENINGITIS. Leucocytosis is usually well marked. Von Limbeck considers that tuberculous meningitis can be distinguished from purulent by the absence of leucocytosis in tuberculous cases, but Osler’ states that many cases of tuberculous meningitis do have leucocytosis through- out their course, and my own observations (see Table XXVIII.) tend to confirm this. Of Rieder’s cases, one had leucocytosis and one did not. Zappert’s case had 11,130 white cells, and Ziemke one with 17,500. It seems, therefore, that we sometimes have here an ex- 1“ Practice of Medicine,” 2d edition. EPIDEMIC CEREBRO-SPINAL MENINGITIS. 267 ception to the rule that tuberculous processes do not produce leuco- cytosis. Certainly some cases do follow this rule. But however this may be, it is certain that purulent meningitis, whether second- ary or of unknown origin, is characterized by high leucocyte counts, and if in a case evidently of meningitis of some kind leucocytosis is absent, the case is probably tuberculous in origin. TaBLE XXVIII.—MEnrnaitis. = Per cent . é . | White - marks. gs Age § Red cells. cells. nan Rel 8 1} 19 ) ea il Se isracianaes 4,000 14 | F. | 3.720,000} 4,400 45 |Autopsy. 265) aay Whonsnscceaastts 4,600 .. |First week. 3,400 Sixth week. 51 | M. | 4,664,000) 4,800 Autopsy. Chronic phthisis also. 23.) Me | ca sreaisacis 4,900 .. |Autopsy. Differential count normal. T4 cio a eeaisan 5,400 65 18.) Be |) sesaeaies 5,400 80 |September 21st. 7,400 = September 24th. No serum reaction. 29° | Ma. Ils casiencis 5,600 64 |Autopsy. No serum reaction. TQ SRY Weise Aeneas 6,100 .. |Autopsy. 19°) ES || wased nae 6.600 Autopsy. 5G" | sss~ lt ieeeiveeeaes 6,800 First day. 8,200 Ninth day. 21,000 ag Day of death. BH | Be | a eeses oe 7,500 71 |Autopsy. AS) ve: | Seckee ers 7,600 .. |First day. 8,600 Fourth day. Ninth, death. 36 | M. | ........ 7,600 Healed phthisis also. Autopsy. 200) Be cesaeaaas 7,800 May 14th. 7.200 a May 22d, death. Autopsy. 85 | .. | 3,920,000) 8,000 45 30; .. | 4,500,000, 8,800 52 BO: | UM. | acted 9,250 .. {April 18th. 9,450 April 20th. Autopsy. 45 | M. | 5,237,000} 10,000 Autopsy. BEI ll ean Beies eee 12,200 Autopsy. 22) I Mis | ears'se a's 12,700 Phthisis also. Autopsy. 280 SPECIAL PATHOLOGY OF THE BLOOD. TaBLE XXXII.—AcuTE Miuiary Tusercu.osis (Continued). ‘ Per cent Age.| Sex. | Redcells.| White | hemo- Remarks. cells. globin. 78 | .. | 2,416,000; 32,000 29 Diff. count 1,000 cells: Polynuclear, 87 per cent. Lymphocytes, 11 7 Eosinophiles, 0 = Myelocytes, 2 . Normoblasts = 5. Megaloblasts = 2. Complicated with diphtheria. Case I. of the above table is a striking example of the remark- ably low leucocyte count sometimes seen in this disease. The counts were carefully verified by several competent observers. Qualitative Changes. In Warthin’s case above quoted, he repeatedly made differential counts of the leucocytes by Ehrlich’s methods, with this average result: Polymorphonuclear neutrophiles..................4. 91.49 per cent. LyMphocytes (SMAI!) vcciss cc. ewe waswwiens save sidiae eee ds 5.52 st Lymphocytes (large and transitional)................ 3.09 * Hosinephiles. ..5.scni0 va cea css wilewa ere ares dsews econ 0. v My Glo yibei ye cccka inte y boos eats sp beam aesediecs 2. IV. TUBERCULOSIS OF SEROUS MEMBRANES. 1. TupEercuLous PERITONITIS. The blood condition is exactly as in other forms of tuberculosis, except in so far as it is modified by the drain exerted on the blood by diarrhoea or by transudation or exudation into the peritoneal cavity. Such events concentrate the blood by withdrawing water and albumin from it and may give us a normal number of red cells per cubic millimetre, when in reality a considerable anemia is pres- ent. As arule, the blood shows a mild secondary anemia without leucocytosis or with leucopenia. This is exemplified in the follow- ing table from the Massachusetts General Hospital records: TUBERCULOSIS OF SEROUS MEMBRANES. 281 TABLE X XXIII. Age.| Sex. | Red cells. | White tee Remarks. cells. globin. 26 | F. | 8,120,000) 2,240 58 OS. ae | aeeeeeas 2,600 33 | F. | 2,900,000] 3,800 48 24 | M. | 5,360,000} 3,800 .. |January 6th, 1896. 5,760,000) 5,600 85 |April 18th, 1896. BO WOK Wee case ance 3,900 se Tuberculous tube. 21) ME | xe sed gale 4,400 29)')) we) aeaeeeees 4,700 52 Bet [Me A] ged este aed 4,900 64 |March 1st. aphasia 5,500 i March 9th. 43 |M.]........ 5,000 ne December 18th, 1895. 4,560,000) 3,250 76 =|January 10th, 1895. S100} Hiss il Spacitentag 5,180 i Tuberculous tube. 20 | F. | 5,936,000) 5,400 O28 | se || axes seinen 5,400 44 | M. | 2,974,000) 5,530 Pleuritic effusion also. ee Nas pet tr cep 5,600 A || cases Wh eeaseaseaals 5,600 16 | F. | 3,840,000) 6,000 33 | F. | 4,000,000; 6,000 Bit Ge eutaree tes 6,200 5,400 50 | F. | 5,240,000; 6,400 BBE aie Wie etic 6,400 55 Bi | Me Ih ca gescemuare 6,700 -. |May 22d, 1896. 22] .. | 8,552,000) 6,800 45 15 5,112,000; 6,900 70 |Polynuclear, 44 per cent; lympho- WO ou Wi vevewes 7,200 cytes, 49 per cent; eosinophiles, 7 per cent. AG: 2. |) ayeonees 7,400 70 £5! xe || saatennees 7,400 BS OW Sie eeee wach 6,800 BSE - ate. | esade en mesee 7,900 BL. |! [Os oenacurs 8,000 28 See Ul ie aera ed 8,000 37 wag W Aaeatert eas 7,500 30 gt | ahh Say 7,500 26 MEW coscca sna 7,500 21 M. | 4,800,000 | 7,500 65 30 Ms |) saced nes 7,400 64 30 NT Al Sass stents 7,300 53 M. | 4,240,000 | 6,798 79 24 Seise W ceuncavs, SOs 6,300 44 heat Ne aapeetnachat 6,200] .... |Obstruction. 29 My | scaarmyn 6,200 82 ie M. | 4,996,000 | 6,000 78 24 So'| Sean aes 6,000 73 25 ieee || aeeanepete s 5,400 30 |Polynuclear, 78 per cent. Lymphocytes, 19 " Eosinophiles, 1 7 Myelocytes, ee ie a (2)" Reds pale, deformed. 1 normoblast. 32 ead (I kephagecenaness 5,800 | .... |March 16th. 5,600,000 | 4,700 75 35 M. | 4,350,000 | 4,900 85 44 .. | 3,168,000 | 4,800 85 29 Be. | igkengasanes 4,200 85 9,600 19 Fs | apaeaiee 4,000 and the red cells and hemoglobin have not suffered except in the alcoholic case in which other causes for anemia were present. This is contrary to the observations of Grawitz, who found constantly leucocytosis, but agrees with those of v. Limbeck and Hayem, who never found any increase of leucocytes or any other changes in the blood count. Coagulation in this or any other type of obstructive jaundice may be very slow, but this is especially apt to be true in gall-stone cases even if no jaundice is present. Coagulation may be increased to eleven minutes (Osler) and patients may bleed to death during operation on gall stones. The amount of fibrin is normal. Von Limbeck noticed an increased resistance of the red cells to the influence of distilled water and dilute saline solutions which in normal blood dissolve the hemoglobin. He noticed also that the size of the red corpuscles was greater than normal, their 20 306 SPECIAL PATHOLOGY OF THE BLOOD. volume in a given amount of blood being seventy-seven to eigkty- one per cent (7.e., they take up seventy-seven to eighty-one per cent of the room occupied by the drop), while the normal is about forty- four per cent. This was in cases with only from 4,000,000 to 5,200,000 red cells’ per cubic millimetre, so that it was evidently due not to an overcrowding of the drop with red cells, but to a true increase of size in the individual cells. The same fact has been attested from a different point of view by the investigations of v. Noorden, who found the solid residue increased, and of Hammer- schlag; and Grawitz has noted an increase in the specific gravity of the whole blood, though that of the serum remained normal. WNor- mal red corpuscles put into the serum of icteric patients increase their diameter considerably, so that apparently the serum is respon- sible for the change. Qualitutive Changes. Grawitz noted in severe cases that crenation took place much more rapidly than usual in freshly drawn blood, and that the rou- leaux formation did not take place. This latter point was also noticed by Hofmeier' in icterus of the new-born. Silbermann’ noticed in the same disease great deformities in the size and shape of the cells. In severe febrile icterus Weintraud noted in the red cells the white spots and streaks with active (molecular) movements described by Maragliano (see p. 83) as endoglobular degenerative changes. Summary. Normal blood, except for increased size of the red cells and some degenerative changes in severe cases. Diagnostic Value. The constant presence of leucocytosis excludes an uncomplicated “catarrhal” jaundice, and points to the probability of malignant disease or inflammation (cholangitis, abscess). Syphilis and cir- rhosis of the liver might show the same condition of the blood un- less the characteristics of syphilitic blood were very marked (see p. 286). From a severe choleemia the absence of any marked anemia distinguishes a purely catarrhal case. (For the changes in cholemia see p. 312). 1“Die Gelbsucht der Neugeborenen,” Stuttgart, 1882. *“Die Gelbsucht der Neugeborenen.” Arch. f. Kinderheilk., 1887, p. 401. CIRRHOSIS OF THE LIVER. 307 CIRRHOSIS OF THE LIVER. 1. Orpinary (ATROPHIC) CrirRHOSIS WITHOUT JAUNDICE. In the early stages (according to Hayem) neither the red cells nor the hemoglobin fall considerably. Most other observers (per- haps thinking chiefly of the later stages) report marked anemia. Wlajew' counted from 3,000,000 to 4,000,000 red cells; v. Lim- beck had a case with only 1,500,000. He noted that the count might be increased after a tapping in cases with ascites, owing to the concentration of the blood from the rapid refilling of the belly with serum. Grawitz, on the other hand, noticed precisely the op- posite effect in a patient whose blood before tapping had been con- centrated by cyanosis, the heart’s action being embarrassed by the ascites. After tapping, when the heart’s action had become easier and stronger, the cyanosis disappeared and the blood count fell from 4,700,000 to 4,300,000. In v. Limbeck’s case it rose from 4,680,000 to 5,160,000. The moral is that we should draw no in- ferences from the count of red cells soon after a tapping. The thirty-seven cases in Table XLIV., A., were all advanced and their red cells averaged only 3,580,000 + per cubic millimetre. They steadily decrease as the disease progresses, one case getting as low as 1,300,000; but the anaemia may be concealed by cyanosis and concentration. Qualitative Changes. Hayem noticed a curious stickiness of the red corpuscles, a great tendency to adhere to each other. Von Limbeck looked for it, but could never find it. Hayem and Maragliano noticed degenerative endoglobular changes in the red cells (“ état cribrifogme”). TaBLE XLIV., A.—Crrruotic LIVER WITHOUT JAUNDICE. Per cent Age.| Sex.| Red cells. | White cells. | hamo- Remarks. globin. 58 | .. | 4,504,000) 29,300 60 |T., 100°. Delirium tremens. 18,500 .. |Fourth day. 35 |... 908,000 26,000 20 Intestinal hemorrhage. Diff. count 500 cells: Polynuclear, 85 per cent. Lymphocytes, 14 - Eosinophiles, 8 Myelocytes, a Normoblasts, 10 Megaloblasts, 0 1,732,000 | 19,800 25 |Seventh day. Diff. count 500 cells: Polynuclear, 88 per cent. ' Ref. in Petersburger med. Woch., 1894, No. 43. 308 SPECIAL PATHOLOGY OF THE BLOOD. TaBLe XLIV., A.—Cirruotic LIVER WITHOUT JAUNDICE (Continued). Per cent Age.| Sex.| Red cells. | White cells. | haemo- Remarks. globin. Lymphocytes, 10 per cent. Eosinophiles, Myelocytes, dy Normoblasts, 2 2,456,000 16,900 23 Fourteenth day. 3,098,000 | 14,000 35 ~—« | Thirtieth day. 08: | 2x | «saccwen 23,400 .. |First day. Uremic symptoms. 5,800 es Eleventh day. Autopsy. OL iat) Ili aeaasoan alone 18,200 30 |Hemoptysis. Autopsy. 53 | F. | 2,950,000) 16,000 .. |Recent hemorrhage. Ba es | a ce wtgsecse 14, 000 .) 26 8, 100 58 | M. 4,800 25 | M. 11,200 56] .. 8, 100 30 | M. 4,500 10 | F. 11,000 33 | M. 7,900 1 | M. 3,000 47 | F. 10,800 14 |M. 7,750 25 | .. 1,400 56 | M. 10,700 15 | F. 7,700 The same wide range is seen in Table LIII., A and B, in which Ihave divided the uremic and the non-uremic cases into separate tables. It will be seen from these that thirty-four out of forty “uremic cases showed leucocytosis, while thirty-nine out of sixty- nine non-uremic cases showed no leucocytosis. It is difficult to suppose that this is mere coincidence. CHRONIC INTERSTITIAL NEPHRITIS. 833 CHRONIC INTERSTITIAL NEPHRITIS. Hayem found the fibrin more increased in this form of nephritis than in any other, and the anemia less pronounced. Grawitz distinguishes two stages: I. As long as the heart is strong enough to overcome the increased resistance at the periphery and the disturbances of circu- lation are not marked, the blood is normal. II. When compensatory hypertrophy is no longer sufficient to do the work of forcing the blood through the system, the usual effects of failing compensation (see Heart Disease, page 320) appear (dilution and subsequent concentration of the blood). The white cells are normal. TasLe LIV.—Curonic Dirruse Nepuritis; No Urania. « Per cent Age.| Sex.| Red cells. wae nasties Remarks. a “| globine |--- - ‘ ends 20 | .. | 3,492,000; 389,000 42 |With bronchitis. 26 | .. | 3,500,000; 26,300 50 With acute articular rheumatism. 36 | .. | 2,560,000} 16,100 35 [April 14th. 12,400. 20 = =|April 30th. 8,900. .. |May Ist. 37 | .. | 8,144,000) 16,000 40 11 | .. | 3,660,000) 15,600 52 33 | .. | 3,568,000} 14,600 45 22 | .. | 4,272,000} 14,400 45 |Sub-acute. 19 | .. | 5,864,000) 14,300 65 |Amyloid liver and spleen. February 12th. 6,092,000) 13,700 Sa From ear. 5,740,000} 13,700 ed From finger. 24 | .. | 3,824,000; 11,400 55 4,268,000] 13,600 16 | .. | 3,724,000; 11,300 45 85 | .. | 3,164,000] 10,600 50 =| Tertiary syphilis. 42 | .. | 4,228,000} 10,100 65 |didema. 19 | .. | 3,776,000} 10,000 56 |Cardiac hypertrophy. 28 | .. | 4,560,000] 10,000 45 47 | .. | 4,450,000} 9,800 50 21 | .. | 4,080,000) 8,600 70 42 | .. | 8,416,000] 7,000 55 55 | .. | 4,360,000} 6,300 50 «| Ascites. 24 | .. | 4,800,000} 5,700 65 26 | .. | 1,468,000) 3,800 23 |Polynuclear, 70%; lymphocytes, 2389; large lymphocytes, 4.4%; eosinophiles, 2.6%; reds, megaloblasts, 3; normo- blasts, 2; microblasts, 1. Consider- able variation in size; many oval forms; considerable poikilocytosis. 334 SPECIAL PATHOLOGY OF THE BLOOD. TaBLe LIV.—Curonic Dirrusze Neparitis; No UR&MIA (Continued ). Age.| Sex.| Red cells. wee tree Remarks. ” globin. 1,136,000} ...... 19 |Polynuclears,71.8%; lymphocytes, 24.2¢; large lymphocytes, 2.24; eosinophiles, 1.24: myelocytes, 6; megaloblasts, 6; normoblasts, 8. November ith. 1,752,000} ...... 22 Polynuclears, 69.4%; lymphocytes, 25.2%; large lymphocytes, 3.8%; eo- sinophiles, 1.6%; megaloblasts, 4; normoblasts, 2. November 18th. 2,248,000} ...... 30 = |Polynuclears, 65.4%; lymphocytes, 28¢; large lymphocytes, 3%; eosinophiles, 3.4%; basophiles, 2; megaloblasts, 1; normoblasts, 0. November 20th. 2,540,000] ...... 48 |Polynuclears, 70.2¢; lymphocytes, 234; large lymphocytes, 2.6%; eosinophiles, 3.4%; basophiles, .8%. Red variation in size and shape less marked. Megalo- blasts, 1. November 27th. 8,392,000] ...... 60 December 6th. 3,580,000} 5,800 65 |Polynuclears, 79%; lymphocytes, 17.62; large lymphocytes, 1.8%; eosinophiles, 1.6%. Reds stain well; slight poiki- locytosis and variation in size; no nucleated reds. 36 5,060,000} ...... 75 |Hemorrhagic nephritis. TasBLE LIV., A.—CHRonic INTERSTITIAL NEPHRITIS. hit Per cent g Age. | Sex.| Red cells. ae hae Remarks. 1] 29 sll eandaentuanaie 23,700 65 2} 389 | M. | 6,040,381) 19,000 80 |Uremic coma; moribund. 3] .... | F. | 4,548,000} 15,000 50 Uremic; mitral stenosis. 4| 68 .. | 3,872,000] 14,000 55 General paresis. 5| Adult} M. | 4,244,000] 12,000 67 |Three and one-half hours after a meal. 6} 22 .. | 5,020,000) 11,200 50 TAGs WaMhe. | scvaacnave.« 9,724 ai Uremic; moribund. 8} 47 ne ee ee 7,300 9| 20 | M. | 4,088,000) 6,000 66 = |March 28d. 52. |March 80th. 10} 384 | F. | 3,586,000} 8,300 57 11} 69 | M.]........ 8,500 87 12); 82 |M.]........ 6,000 65 13} 60 ox WP sear ceevana 5,900 ae With mitral disease. STONE IN THE KIDNEY. 335 PYELO-NEPHRITIS. Table LIV., B, speaks for itself. The anemia is often severe and leucocytosis is the rule. TaBLeE LIV., B.—PyYEe.Lo-NEPuHRITIS. | White Per cent g Age. | Sex.| Red cells. cells, nen Remarks. 1} 24 | F. | 8,056,000} 21,200 41 March 10th. Ursemia. 2,976,000} 15,200 88 {March 138th. 2,696,000} 18,800 33 |March 27th. 3,272,000} 25,200 33 | April 14th. 2} 26 | F. | 4,200,000} 16,800 As Perinephritic abscess too. 3} 33 | M. | 4,536,000) 15,550 36 = |Cystitis also. 4) 26 | F. | 2,856,000) 7,280 65 = |Cystitis also. 5} 40 sae. |: ee Es ohare 6,800 at Pyelitis. Tasie LIV., C.—Cystic Kipney. Whit Per cent g Age. |Sex.| Red cells. eatlee Laue Remarks. 1} 55 | M. | 3,664,000) 6,400 is Adult cells, 72 percent. Supposed cancer. Enormous firm tumor on each side. Autopsy. The cases recorded in Table LIV., A, are probably not incon- sistent with these rules. Of the seven cases with leucocytosis three were uremic, and in a fourth the influence of digestion is seen. The hemoglobin is lower than we should expect from Grawitz’s account. Uremia, it would appear from these tables, may cause leucocy- tosis, or at any rate is not infrequently associated with it. Aside from uremia and hemorrhage, nephritis, probably does not cause leucocytosis. STONE IN THE KIDNEY. (See Table LV., A.) The state of the blood depends on the amount of ulceration caused by the stone; when this is considerable we have leucocytosis. 336 SPECIAL PATHOLOGY OF THE BLOOD. TasLe LY., A.—STONE IN THE KIDNEY. | Per cent o| Age.’ Sex. | Red cells. | White cells.} hzemo- Remarks. Zz, globin. Dl 2se-|l|) ota) wet y 22,800 85 _|Tender in loin. 16,200 QOL ti kl ehaeat 16,500 August 10th. 10,800 August 12th. Pain gone. Bl AG | Moy |) cseaaves 15,200 44 Much pus in urine. 4| .. | M. | 4,850,000) 14,750 78 5} 53 a aebendeend 12,900 73 Ch 20 Wl call ead wkcken 10,200 7| 25 | F. | 4,160,000) 9,000 65 8} 48 | M.] ........ 8,990 9} 58 | M. | 5,680,000; 8,000 10) .. | .. | 4,840,000) 3,000 ua Much pus in urine. 6,100,000} 16,500 ke Two weeks later. 11) 52 | M. | 8,048,000) 7,500 30 12) 450} Me | ccdaccacesc 7,500 95 13) 51 | M. | ........ 6,000 95 |Uric-acid stone passed. 14) 80 | M.| ........ 4,980 85 Diagnostic Value. a2 iinet Cancer would also cause leucocytosis, but would not increase fibrin as a rule, while most cases of stone with ulceration do increase fibrin. The blood is normal. FLOATING KIDNEY. This fact has some diagnostic value; for example, when we confound appendicitis with floating kidney, as has been done (see page 247). The presence of leucocytosis ex- cludes the latter and favors the former. Most tumors or abscesses with which a floating kidney might be confused could be distin- guished by the same criterion. TaBLe LY., B.—FuLoatina Kwney. Per cent ¢ | Age.) Sex.| Red cells. |White cells.; heemo- Remarks. Z globin. 1| 47 4,650,000) 23,000 45 |March 28th. Peritoneal inflamma- tion. 17,400 April 4th. 21,300 April 9th. 21,800 April 15th. Diff. count 300. _Poly- nuclear, 87 per cent; small lym- phocytes, 7; large lymphocytes, 5.5; eosinophiles, .5; reds aver- age size; very few poikilocytes. BRONCHITIS. 337 TaBLEe LY., B.—Fioatine Kipney (Continued). Per cent ¢ | Age.| Sex. | Red cells. |White cells.| heemo- Remarks. a globin. 2} 65 | .. | 4,422,000) 11,800 65 |Double. Oh ek: il oa. | sige setae 11,200 70 4| 87 | F. | 5,056,000] 9,200 vis) 5} 41 | F. | 4,684,000) 9,000 75 6] 24] FL] ........ 8,100 EST | Wee ceteris 8,000 65 8} 23 | F. | 5,400,000) 6,000 69 9} 43 | F. | 4,700,000) 2,400 76 1.0) BS ell ceesecceosce |) a eeteeinidee 75 |Aneurism of arch also. | aol Wel esas! Acs oenty 80 12} 388 | F. | 4,416,000) 5,800 67 BB) 2A Weel) eierseanceey 7,600 80 A large number of similar counts might be quoted. HYDRONEPHROSIS. TaBLe LVI., C.—HyYDRONEPHROSIS. Per cent Age. |Sex.| Red cells. | White cells. | haemo- Remarks. globin. 52 | .. | 4,016,000 16,400 75 March 7th. 10,800 ’ New York Med. Journal, May 22d, 1897. EMPHYSEMA AND ASTHMA. 341 January 26th. February 4th. February 11th. Red cells.............. 38,911,000 4, 221.000 4, 630,000 White cells............ 8,300 7,500 7,600 Heemoglobin.......... 68 percent. | 75 per cent. 86 per cent. Polymorphonuclear Cells :ycmuses nea ae kate 36 te Lymphocytes (small) .. 5 i. Lymphocytes (large) .. 5.2 * Eosinophiles........... 53.6! “ 38.2 per cent. | 33.9 per cent. Few normoblasts| ........ No nucleated red cells. Their presence in increased numbers before a paroxysm is said to make it possible to predict its coming (v. Noorden, Schwerskewski). Coler reports a case of asthma with a leucocytosis of 52,000, 25 per cent of which was made up of eosinophiles. The case was complicated with extensive purpura, painful muscles, and extreme cyanosis, but microscopic examination of the affected muscles showed no trichine. I have watched one subacute case without well-marked parox- ysms or periods of perfect health. The blood was frequently exam- ined and showed always a slight leucocytosis with 11 to 15 per cent of eosinophiles. As this applies only to pure bronchial asthma and not to cases secondary to disease of the heart or kidney, Schreiber states that we are enabled to distinguish bronchial from cardiac or renal asthma by the increase of eosinophiles in the blood and sputa in bronchial cases, which does not occur in asthma due to cardiac and renal trouble. Other records are (Gabritschewsky) : Case I.—White cells. 2.0... 0... ce eee eee 8,200 Eosinophiles..................0.00- 10.8 per cent. Case II.—White cells............ 00... eee ee 6,800 EHosinophiles...............000000. 22.4 per cent. POlYMUCICATS: 5.5 ccscccscecsiecs e's BA wie aoa 35 " ASTHMA. ‘ Per cent White Age.| Sex.| Red cells. ols eee Remarks. 26: | Me | wecaas 32, 500 ee Fifth. Temperature 100°. Bron- chitis and emphysema. 19, 200 ae Seventh. Temperature normal. 0 Bs | avszeses 19,800 50 Typical bronchial asthma during paroxysm. 70 | M. | 5,500,000 | 138,000 a Chronic asthma and emphysema in paroxysm ; polynuclear cells, 79 per cent. 29-1 Me) ea eens 9,750 342 SPECIAL PATHOLOGY OF THE BLOOD. For Pneumonia, see page 189. For Phthisis, see page 271. For Abscess of Lung, see page 252. SYPHILIS OF THE LUNG. In a case of syphilitic infiltration of the lung (autopsy—Drs. Councilman and Wright) recently observed at the Massachusetts General Hospital the leucocytes rose rapidly from 8,700 to 27,400 as death approached. GANGRENE OF LUNG AND ABSCESS. Age. | Red cells. | White cells. |, ‘Per cent Remarks. hemoglobin. 49 | w..ae 39,900 =) Abscess, autopsy. BQ i cosereadea’s 22,400 + Abscess after grippe. IQ) comets 18,400 a Gangrene. 48 | wwesics 16,400 es Abscess after immersion. OF | aamea 15,300 a First day. Gangrene. 20,500 Fourteenth day. 18,800 Sixteenth day. 23,000 Nineteenth day. 27,000 Twenty-first day. 27,000 Twenty-sixth day. 31,000 Twenty-ninth day. 17,000 Thirty-second day. Better. 20,000 Thirty-sixth day. 15,800 Fifty-fourth day. B00 f Sesewsevs 9,600 ih Gangrene. PART V. DISEASES OF THE NERVOUS SYSTEM, CON- STITUTIONAL DISEASES, AND HEMOR- RHAGIC DISEASES CHAPTER VIII. DISEASES OF THE NERVOUS SYSTEM. NEURITIS. Iw cases of multiple neuritis, febrile and apparently of an infec- tious nature, the following counts are found in the. records of the Massachusetts General Hospital : Age.| Sex. | Red cells. | White cells. mesa aa Remarks. 4,816,000 | 25,000 42 July 10th. Temperature, 101°. 24,800 July 18th. 18,700 July 16th. 21,000 July 20th. 4,320,000 | 16,000 60 July 25th. 28,700 July 31st. No fever. 19,500 August 7th. No fever. 23,200 August 20th. No fever. SA || Sanda 8,400 a8 Polynuclear, 362. Lymphocytes, 62%. Eosinophiles, 2 (Count, 800 cells.) 22 Ga | anesthe 6,400 The first case, a boy of eleven, recovered and left the hospital well. But these changes occur also in alcoholic (afebrile) neuritis, as the following counts show: 344 SPECIAL PATHOLOGY OF THE BLOOD. -Age.| Sex.| Red cells. | White cells. Hismonlonia Remarks. AAS Babel, eske sleet, 16,100 ae Pneumonia. No autopsy. eile 8,608,000 | 15,000 75 8,260,000] 14,000 64 oe etal pees 18,700 60 39 | .. | 3,584,000] 12,000 45 os de Mattes eee 11,200 68 oe lates eeees aang 7,700 80 QO” || a; IV aease etna 7,600 is apsall ese etcenacn a eae 6,700 82 In all cases the counts were made just at meal time, so that the leucocytosis is not due to digestion. Gastritis was not present in either case. One case of post-diphtheritic neuritis in a child of eight showed the presence of anemia only: Red cells, 3,850,000; white cells, 7,393; hemoglobin, 70 per cent. Neuritis in lead poisoning does not affect the count of leuco- cytes, as twenty-five cases studied at the Massachusetts General Hospital have shown. HERPES ZOSTER. No.} Age. | Red cells. | White cells. henielonie Remarks. Toh Beh ieee een 15,500 we Temperature 99°. *D| TAs V aiea wage 2 9,100 ees [08 bce dys 8,500 60 Neuralgia, whether facial, intercostal, sciatic, or ovarian, showed normal blood in numerous cases examined at the Massachusetts General Hospital. DISEASES OF THE BRAIN. Meningitis (see Inflammation of Serous Membranes, page 266). Zappert in one case of brain abscess found only 4,000 white cells. In pachymeningitis hemorrhagica and cerebral syphilis (one case ‘of each) v. Jaksch found leucocytosis. My own experience has been the same. Cerebral and cerebellar tumors have no effect on the blood as far -as could be judged from nine counts in the former and three in the latter disease. Von Jaksch found slight leucocytosis in two cases of brain tumor and one of cysticercosis. Zappert found normal blood in one case of cerebral tumor. DISEASES OF THE BRAIN. 845 TaspLeE LVII.—CEREBRAL TuMOR. er cent Age.| Sex.| Red cells. ane Teme Remarks. globin. BO 5 | eased eas 18,100 70 BB} as | eavaseas 16,900 75 RQ]. | eee ee. 15,000 LDP | ater | eiet noes 2 14,500 13,700 260) aah] eanacare 12,500 Be | ash | Mestetee Se 12,200 70 QT | se | waeeease 10,600 60 88 | so | aeyesces 9,000 72 02. | ee" amae ees 7,000 BL a cca IP eeldintarae 9 4,100 Fresh cerebral hemorrhage usually causes leucocytosis, as the following table shows: TaBLE LVIII.—CEREBRAL HEMORRHAGE. Per cent | Sex.| Redcells. | White | “neemo- Remarks. cells. globin. VEE atetevasp enaus 31,000 95 Autopsy. ANTE. Il cece set 30,000 ste Polynuclear cells, 924. 5,512,000 | 25,000 85 Autopsy. Serena 29,700 i Autopsy. skeet ayes 23,600 26,000 ae Second day. soe| Gerster 22,200 “4 Coma. mrss |b eganealatst ats 19,800 Me. | states 4 os 19,400 “i Autopsy. ax '| eee e4 19,000 65 ei a] salimaaeees 17,400 100 Coma. Hemiplegia. Bin |) 8 cesetisusears 16,800 68 Hemorrhage four days before count. Autopsy. 5,560,000} 15,600 90 ie is wrsktiad aeaty 16,000 pase {ll resstapeaase > 14,900 Ss Temperature, 104.7°. Died. cg | seacmears 13,800 3 Hemiplegia. Died. ee Wbtes areteanare 13,000 2 Hemiplegia. Coma. Mba seececcisnecs 12,300 70 Sar il edenatavaeeks 12,000 11,900 ats No coma. dra. | sce eat 11,800 Sd eorarereat nce 11,600 M,..). es cxseag 10,400 58 Conscious ; recovered. Mo | sasssaas 10,300 90 Autopsy. Ms || a eeecerteans 10,200 60 aided | catch Aegan 10,200 10 952,000 5,200 18 Arterio-sclerosis; emphysema of lungs ; pernicious anemia. Tem- perature, 102°. Polynuclear, 84.2¢. Lymphocytes, 13.82. Eosinophiles, .8%. Myelocytes, .8%. Basophiles, .22. ’ Megaloblasts = 6. 346 SPECIAL PATHOLOGY OF THE BLOOD. CAISSON DISEASE. Age, White cells. ng ile Va edie ay BRNO ECR TA eee Deg We ep FU tle Men 18,900 OO sa swace yee eas 4 ene e sa eee Se eee a ee eG Sualneden wsie-a3s 10,700 CHOREA AND TETANY. Chorea showed in twelve cases normal blood except for increased: percentages of eosinophiles, as in Zappert’s four cases, counted 630— 1,360 (8-19 per cent of eosins). Burr has made a careful study of the blood in thirty-six cases. and arrived at the following conclusions: There is usually a slight diminution in red cells and a moderate diminution in hemoglobin. Any severe grade of anemia is due to some complication. He did not record the leucocytes. Tetany shows no blood changes. DISEASES OF THE SPINAL CORD. Chronic diseases of the spinal cord, such as tabes dorsalis, syr- ingomyelia, spastic paraplegia, diffuse myelitis, paralysis agitans, and progressive muscular atrophy, are found to produce no changes. in the blood. For Spinal Meningitis, see page 267. GENERAL PARALYSIS OF THE INSANE. Capps’ has made a careful study of the blood in nineteen cases and comes to the following conclusions: 1. Red corpuscles and hemoglobin are always slightly dimin- ished, the averages being 4,789,900 and 85 per cent. 2. Most cases show a slight leucocytosis—22 per cent above the normal on the average. Early cases may have no leucocytosis. 3. The differential counts show that the blood is slightly older than that of normal adults. The polymorphonuclear leucocytes average nearly 74 per cent and the smaller forms of lymphocytes only 14.2 per cent, while the larger forms of lymphocytes are rela- tively numerous, averaging 7.8 per cent. In a few cases the eosinophiles were very numerous’ (8.7 and 6.4 per cent). 4. At the time of convulsions the red cells and hemoglobin are ' American Journal of the Medical Sciences, July, 1896. * Roncoroni (Archiv di Psichiat. Scien., 1894, p. 293) finds eosinophiles in- creased even to twenty-five per cent in the agitated and violent cases. HYSTERIA AND NEURASTHENIA. ‘ 347 apparently increased (due no doubt to the violent muscular contrac- tions which raise blood pressure and concentrate the blood, or to cyanosis). There is a sudden and pronounced increase in the leucocytes during and after convulsions or apoplectiform attacks. That this. is not due to concentration of the blood or to stasis, Capps thinks is shown by the fact that not only the number, but the differential count of white cells shows changes, the “large mononuclear” cells being relatively increased, sometimes as high as 25 per cent. Myelo- cytes were seen in one case after the convulsions, and especially just before death, when in a leucocytosis of 18,250 11 per cent were myelocytes.’ HYSTERIA AND NEURASTHENIA: HYPOCHONDRIASIS. A large number of cases have been counted at the Massachusetts General Hospital, with a view of excluding other diseases. The blood count is always normal except that in a certain number of the hysterical cases eosinophiles are relatively increased, and that many of the neurasthenics show the increased percentage of lymphocytes which I have alluded to above (page 114) as characteristic of a vari- ety of debilitated conditions. Marked anemia is seldom present, although the hemoglobin is not infrequently as low as 65 per cent. Reinert’ found the hemo- globin under 60 per cent in only 4 out of 48 cases of hysteria, and in none of 36 neurasthenics. The value of the blood examination in such cases, like that of the urine or the lungs in hysteria, is as negative evidence, and in this respect it is important. When the discrepancy between com- ‘1Leucocytosis has been repeatedly noticed in convulsions from various causes. Probably the irritant which causes the motor discharge also acts on the leucocytes by chemotaxis. For example Barrows’ study of 8 cases of insanity with convulsions includes counts of—1, 43,000 leucocytes with 92 per cent of polynuclears; 2, 33,000 leucocytes with 83 per cent of polynuclears; 3, 82,400 leucocytes with 85 per cent of polynuclears and 9 per cent of myelo- cytes; 4, 21,500 leucocytes with 88 per cent of polynuclears. These counts were made immediately after a series of convulsions. The leucocytosis lasted for many hours and showed the characteristics of ordinary infectious leuco- cytosis. In convulsions from improper feeding in infancy I have seen the leuco- cytes rise from 13,500 before the fit to 27,800 after it. 2 Minch. med. Woch., 1805, No. 14. 348 SPECIAL PATHOLOGY OF THE BLOOD. plaints and signs is great, we want to be doubly sure that nothing hidden escapes our notice, and the blood examination is one of the most valuable adjuvants we have in the discovery of deep-seated inflammation or malignant disease, as well as in giving us a general measure of the patient’s degree of bodily health as distinguished from nervous force. The former may be high when the latter is low, or both may be low, and the distinction marks out two classes of cases in which somewhat different treatment is appropriate. There is no use in undertaking to make “blood and fat” when the patient has already plenty of each, though it may be well to carry out the same régime as a matter of suggestion. ‘MENTAL DISEASES. The association of anemia with insanity is too frequent to be a mere coincidence, though it is hard to make either serve as a cause for the other. Very possibly they should both be looked upon as symptoms of a common underlying (unknown) cause. This form of anemia has been noticed by Houston’ in melan- cholia and general paralysis, and by Smith’ in various forms of insanity. Krypiakiewicz’ noticed an increase of eosinophiles in acute forms of insanity, but not in the chronic forms. The /ewcocytosis of acute delirium* is exemplified by the following case from the Massachu- setts General Hospital records: A girl of fifteen; acute delirium; leucocytes, 12,750; no food for eight hours; red cells, 4,510,000; hemoglobin, 63 per cent. Puerperal mania is to be distinguished from the delirium of puerperal sepsis by the fact that the latter shows leucocytosis with increased percentage of polymorphonuclear cells, while the former has no leucocytosis (if uncomplicated) and the eosinophiles are apt to be increased ° (diminished in sepsis). A case of puerperal mania seen by the writer showed: Red cells, 5,210,000; white cells, 6,500; hemoglobin, 84 per cent; eosino- philes, 8 per cent. ‘Houston: Boston Med. and Surg. Journal, January 11th, 1894. ?Smith: Jour. of Ment. Sci., October, 1890. 3 Krypiakiewicz: Wien. med. Woch., 1892, No. 25. ‘Ref. in Klein-Volkmann’s “Sammlung klin. Vortrige,” December, 1893. 5 Neusser: Loc. cit. DIABETES. 349 CONSTITUTIONAL DISEASES. OBESITY. Oertel distinguishes a plethoric and an anemic form of obesity not mevely clinically, but by the evidence of post-mortem examina- tions. He believes that there is a real over-filling of the vessels in the first. The second form occurs most often in women. Kisch examined (with v. Fleisch]’s instrument) the hemoglobin of 100 obese patients; 79 showed over 100 per cent of hemoglobin, 1 reaching 120 per cent, while the other 21 were anemic. DIABETES. There is nothing characteristic about the blood except the in- creased amount of sugar to be detected (.57 per cent as against .1 per cent normally); but this is not a clinically applicable test. Two simple tests for diabetic blood have recently attracted at- tention : 1. Bremer’s test: Heat thick-spread blood films to 135° C.; cool and stain with one-per-cent aqueous solution of Congo red for two minutes. The blood if diabetic looks yellow (to the naked eye). Normal blood similarly treated looks red. Staining with methyl blue also shows a difference between normal blood and diabetic blood. The normal is blue, the diabetic yellowish green. 2. Williamson’s test: Make a mixture of BIGOd Vince esas aectinninsmdak biseeenive 20 c.mm. (2 drops). Aqueous methyl blue (1:6,000)............ 1c.e. Liquor potasse, 60 per cent (sp. gr., 1.058).. 40 c.c. WGC Ieaps @-ioais eras i feras sland, nym cen onal tense Uneanss Scans 40 c.c. Let the mixture stand three to four minutes in boiling water. With diabetic blood the mixture turns yellow, with normal blood it does not. Williamson has found this test positive in eleven diabetics and negative in one hundred cases of other diseases. Bremer claims that by his method cases of diabetes can be recognized before sugar appears in the urine or after it has (temporarily) disappeared. Le Goff confirms the value of the test. Ejichner and Folkel find Bremer’s reaction to be as stated, but find similar color changes in leukemia, Hodgkin’s disease, and Graves’ disease, and changes 350. SPECIAL PATHOLOGY OF THE BLOOD. something like it in a variety of cachectic conditions. Badger has studied the blood of diabetics, leukeemics, cases of Graves’ disease, and other cases at the Massachusetts General Hospital. Only in ‘Graves’ disease did he find reactions like those of diabetic blood. The alkalinity has been said to be greatly diminished, especially in the futal coma, but v. Noorden thinks the tests are unreliable. Fat is often increased in the blood, up to about twelve times the normal, so that the serum is milky, and glycogen has been demon- strated microchemically in the corpuscles. Red Cells. Sugar in the blood draws water from the tissue into the vessels, thereby diluting the blood ; but in a short time the blood frees itself of the excess of sugar and fluid through increased diuresis so as to concentrate the blood. These two alternating influences serve to explain the widely dif- ferent counts of different observers. Toward the end of the disease a decided cachexia often develops, the anemia of which may be temporarily covered up by the concen- tration above noted, or accentuated by the dilution which sometimes occurs. Accordingly we may find the corpuscles increased, normal, or diminished in different cases or at different times with the same case. Grawitz counted 4,900,000 red cells in a patient in comparatively good health, and three weeks later, when the patient had just been seized with the fatal coma, the count showed 6,400,000 per cubic millimetre. The white cells show no constant changes, except that v. Lim- beck has noted in several cases that the digestion-leucocytosis is unusually large even without previous fasting. Von Jaksch found . leucocytosis in one of his eight cases, but on this point as on many others his results are almost unique. The only similar observation is that of Habershon,’ who reports moderate leucocytosis, decreased by strict diet. In thirteen cases I have never seen leucocytosis. ‘One case of diabetic coma showed 45200 leucocytes per cubic milli- metre. Another in a child of eight years showed 49,000 white cells. 1§t. Bartholomew Hosp. Report, 1890, p. 158. MYX@DEMA. 351 GOUT. A few cubic centimetres of serum from gouty blood made acid with acetic acid (six drops of a twenty-eight-per-cent solution to every drachm of serum) deposit crystals of uric acid on a thread in from eighteen to forty-eight hours; but this is not always to be found, and is by no means peculiar to gout.' Uric acid is to be found in the blood in pneumonia, cirrhotic liver, nephritis, grave anemia, leukemia, and gravel; also in health and after a meal of cealf’s thymus or any food containing much nuclein. The red corpuscles show no special changes except in severe chronic cases, which are sometimes anemic. The white cells are increased according to Neusser, while v. Limbeck and Grawitz found the blood wholly normal. It is particularly in this disease that Neusser supposed the “ peri- nuclear basophilic granulations ” to exist in the white cells, which condition he believes to be characteristic of any “uric-acid diathe- sis.” Futcher has conclusively disproved this. Fibrin is increased in acute cases. Ewing states that he found “uniform but moderate anemia in a series of chronic cases examined at Roosevelt Hospital, the patients all coming from the poorer classes. In the chronic cases leucocy- tosis of moderate grade may be observed, but it is difficult to determine its relation to the gouty process, as many of these patients suffer from other complaints.” MYX@DEMA. Le Breton? examined the blood in one case both before and after thyroid treatment, and found that after forty days’ treatment the red cells had risen from 1,750,000 to 2,450,000, the white cells from 4,500 to 9,600, and the hemoglobin from 65 to 68 per cent. The remarkably high color index in this case before treatment (nearly 2.!) corresponds with the observations of Le Breton in the dried specimen, which showed a decided increase in the size of the 1It is important to evaporate the serum at a temperature not above 70° F., otherwise crystals will not form. 2Le Breton: Ref. in Wien. med. Blatter, 1895, p. 49. 352 SPECIAL PATHOLOGY OF THE BLOOD. red corpuscles. He also noticed before instituting the thyroid treat- ment the presence of nucleated red cells and an excess of the poly- morphonuclear form of leucocytes. Under treatment the nucleated red cells disappeared and the lymphocytes rose to their normal per cent. Putnam’ has watched a similar case in which the number of red cells rose from 3,120,000 to 5,700,000 under thyroid treat- ment. Murray‘ has collected 23 cases with blood examinations. Of these cases, 7 showed a normal blood count, 10 were anemic, 4 showed leucocytosis, and 2 exhibited both anemia and leuco- cytosis. Kraepelin’ noticed (like Le Breton) a marked increase in the average diameter of the corpuscles in three cases, even when the count and the hemoglobin were normal. [have had an opportunity to examine the blood in four cases of this disease, but did not find anything remarkable in any one of them. Case. | Red cells. | White cells. Hee BOE Remarks. 1 4,670,000 6,000 87 Count 400 cells: Polynu- 2 4,460,000 8,800 Se clear, 66%; lymphocytes, 3 4,856,000 5,200 80 81.5%; eosinophiles, 2.54; 4 4,012,000 7,900 45 slight deformity of reds; 1 normoblast. Differential counts were made in three cases, and no increase in the size of the corpuscles, such as Le Breton and Kraepelin saw, was present in these cases. The count showed: Case. Polen Lymphocytes. Eosinophiles. TN a aa scheint ee laeamen esata 67 28 5 yg Grek fais eral ratigaaral ake 67 27.8 4.4 D4 Tule Be Ree RES EMI 74 26 1Putnam: Ref. in Murray's article in “Twentieth Century Practice of Medicine,” vol. iv. 2 Murray: “Twentieth Century Practice of Medicine,” vol. iv., p. 710. ’ Kraepelin: Deut. Arch. f. klin. Med., vol. xlix., p. 587. GRAVES’ DISEASE. 853 The increase of eosinophiles in two of these cases may perhaps. be due to the skin troubles in the disease. J. J. Thomas found a few myelocytes in a case of Putnam’s. CRETINISM. Koplik' records the following in two cases of sporadic cretinism : Casx J.—Fifteen months old; advanced stage of disease. He- moglobin, 18 per cent. Casr II.—Red cells, 3,026,000; white cells, 13,500; hemoglo- bin, 105 per cent. This high hemoglobin corresponds to normal fetal blood. The child was nine weeks old, but its backward de- velopment is mirrored in the blood. As the case improved under thyroids the hemoglobin came down. GRAVES’ DISEASE (BASEDOW’S DISEASE; EXOPHTHALMIC GOITRE). The blood is normal, except for an occasional associated chlorosis and sometimes a marked lymphocytosis. In one case I found 51.3 per cent of lymphocytes and 1 per cent of myelocytes in 1,000 leu- cocytes, the polymorphonuclear cells being only 48 per cent; but in fourteen other cases I have never found this again. The same fact has been noticed by Neusser (cited in Klein, oc. cit.). Oppenheimer’ found the red cells and hemoglobin normal in two cases. Von Jaksch’ in one case “complicated with myxcede- ma?” found 3,818,000 red and 8,000 white cells. The association of Graves’ disease with chlorosis is illustrated by two cases from Zappert :* Case. | Red cells. White cells. = Sonali Vivivatdetiacsre tone bircear 2,858,000 3,800 32 Fs Hewas Ke be raa RES 2,738,000 3,800 30 The same writer found eosinophiles much increased (8.5 per cent) in one out of four cases. 1New York Medical Record, October 2d, 1897. 2? Deut. med. Woch., 1889, p. 861. 3 Zeit. f. klin. Med., 1893, p. 187. es 4 Zeit. f. klin. Med., 1893, p. 266. 354 SPECIAL PATHOLOGY OF THE BLOOD. MASSACHUSETTS GENERAL HospPiTaL CASEs. Age. | Sex. Red cells. White cells. Hismnclotin: Remarks. 1 | 44 | M. 3,668,000 2,800 45 Be QTE aver IP Ra aaa 7,300 65 3] 42]... 4,920,000 7,700 60 4} 33] .. 4,464,000 9,800 63 Died. GO) AG oe | evens s ds 12,500 50 Jaauary 13. 4,584,000 12,700 1 January 31. 16,000 56 February 18. 15,000 ay February 15. ADDISON’S DISEASE. Some, but not all, cases are accompanied by marked anemia. Neumann! observed a case in which the symptoms came on acutely and the red cells sank to 1,120,000 per cubic millimetre. During the convalescence which followed, the cells ran up above normal, reaching 7,700,000. Tschirkoff’ reports two cases in which the red cells were re- spectively 3,280,000 and 2,933,000 at the lowest, but whose hemo- globin was extraordinarily high, over 100 per cent in one case. This he found on spectroscopic examination to be due to a great increase of reduced hemoglobin in the corpuscles. Methemoglobin was also noted. The white corpuscles showed no changes, quantitative or quali- tative, except that they contained black pigment granules. Three cases have been examined at the Massachusetts General Hospital. The first, a woman of thirty, showed 6,240,000 red cells with 14,000 white, and 90 per cent of hemoglobin. The differential count of 900 leucocytes showed the following figures: Polymorpho- nuclear cells, 53.4 per cent; lymphocytes, 41 per cent; eosinophiles, 4.5 per cent; myelocytes, .9 per cent. The eosinophiles were very large, some of them eosinophilic myelocytes. The second, a man of forty-two, was very anemic and weak at entrance and showed: Red cells, 2,196,000; white cells, 7,500; hemoglobin, 20 per cent. Differential count of 200 leucocytes showed: Polymorphonuclear cells, 65 per cent; lymphocytes, 31.5 ‘Neumann: Deut. med. Woch., 1894, p. 105. * Zeit. f. klin. Med., 1891, vol. xix., Suppl. Heft 37. OSTEOMALACIA. 355 per cent; eosinophiles, 3.5 per cent; 5 normoblasts; marked poikilocytosis. Under suprarenal extract his blood improved in a month till his red cells numbered 4,700,000; white cells, 9,000; haemoglobin, 65 per cent. The third, a man of fifty-two, showed: October 20th—red cells, 2,848,000; white cells, 4,800; hemoglobin, 45 per cent. Decem- ber 10th—red cells, 2,624,000; white cells, 7,100; hemoglobin, 45 per cent. Differential count: Polynuclear, 74 per cent; small lymphocytes, 22 per cent; large lymphocytes, 4 per cent; eosino- philes, .4 per cent. No nucleated red cells. A fourth patient, kindly sent me by Dr. Rogers, of Dorchester, showed: Red cells, 2,864,000; white cells, 2,000; hemoglobin, 51 per cent. Differential count of 300 cells showed: Polymorphonu- clear cells, 63.3 per cent; lymphocytes, 33.3 per cent; eosinophiles, 2.3 per cent; basophiles, .3 per cent. I have never seen melanin in the leucocytes as Tschirkoff did in his two cases. ADDISON’s DISEASE. Age. | Red cells. - | White cells. | naiCogionin. Remarks. 34 5,056,000 5,000 60 Soon died. 39 5,460,000 117,000 80_ Autopsy. 29 4,804.000 10,000 68 Polynuclear, 77.6 4. Lymphocytes, 14.0 Eosinophiles, 8.0 Myelocytes, .4 519,200 10,400 80 OSTEOMALACIA. The blood has for a long time been supposed, on the authority of v. Jaksch (Zeit. f. klin. Med., vol. xiii., page 360), to exhibit a diminished alkalinity, the bones being supposed to be eaten away by acids in the blood. Von Limbeck and many other observers have lately shown that the blood is normal in alkalescence. Corpuscles and hemoglobin are usually within normal limits quantitatively, but Neusser reports an increase of eosinophiles and the presence of myelocytes in the blood. Ritchie’ confirms Neusser and found also the young leucocytes more numerous than normal. 1Edin. Med. Journal, June, 1896. 356 SPECIAL PATHOLOGY OF THE BLOOD. Fehling,’ Sternberg,' Chrobak' found no increase of eosinophiles. Rieder’s case was normal in all respects: Red cells, 4,892,000; white cells, 5,600; eosinophiles, 3.6 per cent; polymorphonuclear cells, 61 per cent. Ewing says: “The usual condition of the blood in osteomalacia. appears to be that of moderate secondary anemia. The leucocytes. have varied from subnormal to moderately increased numbers. The lymphocytes are usually very numerous, an excessive proportion (maximum 56 per cent) having been found by Tschistowitch. High normal proportions of eosins have been found by several observers,. but not by others.” RICKETS. 1. Anemia is always present in severe cases and often in mod- erate ones. This, together with the fact that many cases of rickets are associated with an enlargement of the spleen, has led to the use of the misleading term “splenic anemia.” There is no form of anemia found in rickets that may not be found in other conditions. (Morse). Hock and Schlesinger found an average of 2,500,000 red cells in a considerable number of cases with and without enlarged spleen. Von Jaksch describes a case in which the red cells sank from 1,600,000 to 750,000 within three months, and Luzet saw a simi- larly rapid process, the cells falling from 2,110,000 to 1,596,000 within three weeks. On the other hand, in Morse’s admirable study of twenty well-marked cases the red cells averaged over 4,500,000 and not a case fell below 3,500,000. 2. The hemoglobin is always relatively low; it averaged 63 per cent in Morse’s cases, a color index of about .7. Felsenthal got. similar results. White Corpuseles. It is often difficult to say whether or not the leucocytes are in- creased, owing to the occurrence of most cases in infants at an age when leucocytes are always higher than in adults—how much higher at any given age depends largely upon the degree of vigor and for- wardness of development of the individual child. In Morse’s series, for example, the average age of the infants is twelve months. And for this age none of the counts in his series. 1 Cited by Ritchie (loc. ctt.). RICKETS. 357 seem to me necessarily abnormal. They are all under 16,000 ex- cept three, these three being 17,900, 18,800, and 22,000 respec- tively, the latter in a nine months’ infant. Many of the counts seem to me subnormal for infancy (5,500, 7,200). Most observers find leucocytosis present in many cases, but not in all. QUALITATIVE CHANGES. Red Cells. As in all anemias of infants, the “degenerative ” and “regener- ative” changes are relatively common. Polychromatophilic forms and nucleated corpuscles are fre- quently to be found, the latter often in great numbers but with a majority of the normoblast type. White Cells. Lymphocytosis is said to be marked, but, as with the question of leucocytosis, we are never quite suce whether the numbers are abnormal for that age, for lymphocytosis is the normal condition in infants’ blood. When, however, as in acase mentioned by Rieder, we find 75 lymphocytes in every 100 leucocytes, the child being four years old, we are surely dealing with a pathological condition. Another of his cases, aseven-months’ child, rachitic, with 57 per cent of lymph- ocytes, seems to fall within normal limits. Not so with Morse’s cases. The highest percentage of lymphocytes in his series was 69, in an infant of twomonths. I have similar counts in health at that age. The average of his twenty cases is 43 per cent, which is, if anything, rather low for that age. The same difficulty arises with regard to the reports of eosinophilia in rickets, since eosinophiles are always relatively numerous in infancy. Morse’s highest figure was 7 per cent his average 3 percent. Hock and Schlesinger found 20 per cent in one subject, and Weiss 16 per cent in another. They were highest in cases with splenic tumor. In Rieder’s four cases and in the three seen at the Massachusetts General Hospital, no eosinophilia was present. Myelocytes in small number (.5-.2 per cent) are not uncommon, and may be considerably more nu- merous. CHAPTER IX. BLOOD DESTRUCTION AND HEMORRHAGIC DIS: EASES. PURPURA HAMORRHAGICA. Tue blood is practically that of anemia from hemorrhage (red cells and hemoglobin reduced, white cells increased, occasional nu- cleated red corpuscles or polychromatophilic forms). Agello' has found methemoglobin in the blood, and hence concludes that the disease is a poisoning of the corpuscles by ptomains absorbed from the intestine. The blood plates are much diminished and may be entirely absent in the worst stages. Bacteria of various kinds have been reported in the disease, but negative results are also common, and their presence is probably not significant. The red cells may fall as low as 2,500,000, but are much oftener slightly or not at all diminished. In many mild cases there are no demonstrable blood changes. On the other hand, Osler mentions a case which sank to 1,800,000, and the loss of blood may give rise to a fatal aneemia of the microcyte type (see page 154). Bensaude’ has observed that in 16 cases characterized by large hemorrhages (2 = acute “infectious,” 2 with tuberculosis, 2 chronic, 10 = Werlhof’s disease) the clot shows no retraction and no transu- dation of the serum. Cases with small hemorrhages (toxic, rheu- matic, cachectic, and nervous) do not show any such abnormal characteristics. Hence he concludes that at the outset of a case of purpura, observation of the clotting process may enable us to fore- tell whether or not the case is to be of a severe or of a mild type. He found the blood lesion above described to be greatest during the hemorrhagic crises, slowly disappearing between them. Hayem has confirmed these observations. He finds the fibrin network al- most invisible. Despite this and despite the absence of contraction 1 Riforma Med., Napoli, 1894, p. 108.’ La Semaine Méd., 1897, p. 21. HZMOPHILIA. 359 in the clot, the actual rate of clotting is normal. Hayem has seen similar failure of contraction when the blood plates are plenty. It occasionally occurs in symptomatic purpura (e.g., from phthisis). SCURVY. There are no characteristic blood changes known. When hem- orrhage is severe the red cells may sink very low, to 557,875 in a case of Bouchut’s; Ouskow and Hayem saw counts of 3,500,000 and 4,700,000. ‘The usual qualitative changes of secondary anemia are present in severe cases; hemoglobin suffers as usual more than the count of red cells. Leucocytes may be increased, whether from hemorrhage or from some complicating inflammatory process. This was not so in the following case of my series: January 26th—reds, 3,120,000; whites, 3,600; hemoglobin, 40 per cent. January 29th—reds, 3,600,000, hemoglobin, 55 per cent. Eight days later hemoglobin 65 per cent. “The red cells vary in number and size according to the length and severity of the disease. On account of the frequency of inflam- matory complications and hemorrhages the leucocytes are usually increased, Uskow finding as high as 47,000. Litten, however, ob- served no leucocytosis, and the writer in two well-marked but un- complicated cases found no increase” (Ewing). Barlow’s disease may lower the red cells as far as 976,000—as in a case of Reinert’s—the hemoglobin being 17 per cent. and the white cells 12,000. This was the day before death. The blood plates are not diminished, and the clot retracts normally. HAMOPHILIA. The blood changes are practically those just described and show nothing characteristic of the disease. Coagulation is slower than normal and blood plates are sometimes very scanty. The white cells are sometimes persistently diminished, as in the following cases: L Sept. 11th. | Sept. 14th. | Sept. 17th. | Sept. 20th. | Sept. 23d. | Sept. 24th. Red cells.......-.++ 2,960,000 seas Halace sibs 3,800,000 White cells......... 3,400 3,400 3,800 3,900 3,700 3,300 Heemogiobin ....... 42 per cent. watts es sees 64 per cent.| 49 per cent. 860 SPECIAL PATHOLOGY OF THE BLOOD. II. February 8th. February 28th. 4,400,000 3,600,000 ] 5,000 5,000 { Daily nose-bleed. 30 per cent. 28 per cent. BLOOD DESTRUCTION (HAXMOCYTOLYSIS). I. Besides the slow destruction of corpuscles which takes place in any ordinary anzemia, we have a group of conditions under which a large number of red cells are suddenly destroyed in the circulation itself. This may take place by — 1. Separation of the hemoglobin from the corpuscles so that it colors the seruin. 2. Actual breaking to pieces of the red cells without separation of the hemoglobin. If normal blood is drawn and left to stand, the serum which separates from the corpuscles is not red-tinged or but very slightly so, provided all shaking and jarring are avoided. A very slight reddish tinge may appear in the serum even with most careful tech- nique. In some conditions the hemoglobin, while not actually separated from the corpuscles within the vessels, is so loosely con- nected to them that a considerable quantity separates post mortem and colors the serum in spite of the avoidance of any jar. This condition is to be distinguished from true hemoglobinemia, in which the serum is actually colored before leaving the vessels, although the two condititns really represent only different degrees of vulnerability of the red cells. We are surer of a diagnosis of hemoglobinemia when we find bits of broken-down cells in the fresh blood and the additional evi- dence of hemoglobinuria or jaundice. 1. Severe forms of malaria, yellow fever, typhus fever, severe forms of septicaemia, and rarely scarlet fever may cause hamoglo- binemia. Also alcoholism with fever, nephritis, cirrhosis, grave icterus, quinine poisoning, and eclampsia (Hayem). 2. Paroxysmal hemoglobinemia, so-called, is a variety whose cause is unknown and which does not seem secondary to any other disease, unless a certain relationship to syphilis be established, and tomalaria. The attacks are brought on by a great variety of causes (cold, muscular or mental strain, ete.). Some persons can always bring on an attack by putting the hand or foot into cold water. BLOOD DESTRUCTION (HAMOCYTOLYSIS). 361 Blood Examination. Coagulation is very rapid, but the clot soon dissolves again (Hayem). The fresh blood occasionally shows deformities in the corpuscles or bits of broken cells, and lack of rouleaux if examined duringa paroxysm. Asavule the corpuscles of the peripheral blood look normal. Frazer has recently reported a case in which he ex- eited a paroxysm by a cold bath, and studied the blood with great care. Time. Red cells. | White cells. ee Lai Blood plates. 10 a.m. Before bath ....| 4,075,000 15.000 50 450,000 11:05 a.m. Twenty - five minutes after bath; urine pale. 3,633,300 21,800 50 696,000 11:45 (urine dark)....... 3,760,000 21,300 60 525,000 DAN Be Me cseerd in tstew acne gonus 4,200,000 21,500 50 4,250.000 (!) BYAD) Bediencatss see eos eineles 3,800,000 17,700 50 1,600,000 Next day, 1 p.M......... 4,100,000 18,700 50 500,000 The enormous increase of “blood plates” is striking. It is diffi- eult to resist the conclusion that these blood plates were bits of broken red corpuscles. ‘The serum was currant-jelly colored. The appearance of the corpuscles was quite normal. All that is known of the disease is expressed by saying that for some reason the red cells are abnormally sensitire, so that any one of a variety of slight disturbances is sufficient to separate their hemoglobin and set it loose in the plasma. 3. Extensive bins have been reported to cause hemoglobinemia with breaking up of the red cells, presumably through changes in the serum similar to those which make duodenal ulcer so common a se- quel to bad burns. 4, Snake poison and scorpion poison may have similar effects. IJ. Another group of corpuscle destroyers is that which works by changing the hemoglobin to methemoglobin. The most impor- tant of these is— 1. Chlorate of Potash.—This destroys the corpuscles and pro- duces hemoglobinzmia and the usual train of symptoms (jaundice, dark urine, ete.) due to this. Brandenburg’ examined the blood of a woman who had taken 1 Berliner klin. Woch., 1895, No. 27. 362 SPECIAL PATHOLOGY OF THE BLOOD. two and one-half ounces of chlorate of potash in water the night before. The blood showed marked leucocytosis, broken and dis- torted red cells. In gross it was chocolate-colored and the serum after separation of the clot was brown. The red cells progressively decreased as follows: Red cells. White cells. First: day. ccapi aussie Vee valoss 4,300,000 20,000 Second day owas csccnaasae saiesaed 2,500,000 Fourth day s.a¢20-4s-sasstuweswers ss 2,300,000 Fifth day... ... cc. ccc ececee ees 2,100,000 Sixth day........... cee eee ants 1,900,000 Seventh day ........ ..eece sees ee 1,600,000 15,000 (death). Jacob’ studied a similar case: Thirty hours after a dose of 25 gm. of KCIO, the blood showed: Red cells, 4,425,000; white cells, 80,000 (stained specimen resembles leukemia). Next day, red cells, 1,825,000 (broken and decolorized); white cells, 60,800. Fourth day, red cells, 2,225,000; white cells, 14,000. 2. Ehrlich and Lindenthal’ report the case of a patient who was poisoned with nitrobenzol. Ten hours after the blood was chocolate- colored and showed methemoglobin bands. Under the microscope there were no changes till the third day, when poikilocytosis ap- peared. Per cent | Nucleated Red cells. White cells. heemo- bi fee globin. | snillimetre. Fifth day. secisieosssaacecs ey 2,275,000 | Much increased. 55 2,070 Seventh day.............. 1,845, 000 hd a 50 7,900 Eleventh day............. 1,600, 000 ‘ “ 44 24, 700 (1) Fifteenth day............. 905, 000 -) ie 40 12,000 Seventeenth day.......... 1, 102,000 ¢ e et 1,300 Nineteentn day..... ..... 900, 200 # x ti 540 ef “death. The nucleated red cells were at first mostly normoblasts; later mostly megaloblasts. Posselt* and Boas* have published similar cases. 3. Antipyrin and antifibrin in doses of from thirty to forty- five grains may cause great cyanosis and dangerous prostration 1 Berl. klin. Woch., 1897, No. 27. *Zeit. f. klin. Med., 1896, p. 427. 3 Wien. klin. Woch., 1897, No. 30. Deut. med. Woch., 1897, No. 51. ILLUMINATING GAS POISONING. 363. through the transformation of the hemoglobin and methemo- globin. In certain persons, even much smaller doses produce the same effect. 4, Phenacetin poisoning (Kronig: Berl. klin. Woch., 1895) may cause actual blood destruction with aneemia in case the patient sur- vives the immediate effects of the deprivation of oxygen. A fatal case of chloral poisoning at the Massachusetts General Hospital showed 14,400 leucocytes with 54 per cent of hemoglobin. 5. Phosphorus poisoning (see Liver, page 311). 6. Workers in aniline dyes and nitroglycerine factories may be severely poisoned by nitrobenzol compounds inhaled and producing methemoglobinemia. 7. Pyrogallic acid and pyrogaliol as used in treatment of skin. diseases may lead to death through destruction of the red cells. Chromic acid (for instance, as applied through the vagina) may have a similar effect. Many other less common substances work the same ill effects on. the blood. III. A third group of substances, of which carbonic oxide gas is. the type, poison by combining chemically with the hemoglobin and preventing its combination with the oxygen of the air. 1. Illuminating gas is for our purposes the most important of this group. The appearance of individual blood cells is not altered nor do. they break up, but the corpuscles are useless to breathe with, as. they cannot take up oxygen. The color of the blood is very bright red, much brighter than normal. Red Cells. Von Limbeck' found in two cases 6,630,000 and 5,700,000 re- spectively. The volwme of these corpuscles (estimated by Bleibtreu’s method) was greatly increased, amounting to 70.7 per cent (normal, 41-48 per cent), so that apparently the size of the individual cells is increased. Mimzer and Palma?’ found 5,700,000 red cells in one case. Ehrlich found numerous normoblasts in one case. ' Loe. cit., p. 234, 3 Zeit. f. Heilk., vol. xv., p. 1. 364 SPECIAL PATHOLOGY OF THE BLOOD. Leucocytes. Eaton’ reported four cases, in all of which the white cells were increased, the counts ranging between 15,000 and 22,000 per cubic millimetre. Minzer and Palma (/oc. cit.) found 13,300 in their case. Twenty- four such cases have been examined at the Massachusetts General Hospital with the following results: TasLeE LIX.—ILLUMINATING Gas POISONING. x White Per cent Age. 5 Red cells. cells, Benin Remarks. 41 IME SAP aercuavetct ac 31,200 Coma; recovery. 49 M3) Sake dnees 27,100 September 12th; coma. 19,900 ee September 13th, entirely well. 21 IMG I caveraap thant 26,000 70 Coma; recovery. 19 Ms) auecsen se 25,470 97 50 ie Pewee set 25,200 40 MEX. | -caveitvesie 22,900 %5 21,200 AS November 27th; coma. 15,500 November 29th; convalescent. Adults: |. ce. | xareeaess 22,000 Recovery. 60 IMGs | iy snerstasate.'s 20,400 75 Coma; recovery. 25 Me!) a serene 20,360 | 110 Death. 45 Ms | seeocceaets 20,100 a Coma; death. AMO: | occ |) wee seseenuats 20,000 Ga Nk) Il ee eects 19,600 80 BB | ee lil) ek eaves 18,800 16 RY awe Cargeges 18,500 84 Coma; recovery. QS Ml everett 18,100 80° | as | cas asaes 17,300 90 |Temperature, 101°; recovery. 22 on ie ee 17,100 19 Me inays es ete, 17,000 December 22d. 17,500 December 28d. 4,930,000 | 17,000 Ge | Il santo.) sstecevenet ears 15,600 ibe ise tices 15,000 80 DOr” We xgee F iaiseen es oes 12,000 60 28) ll ase | Saeea ae 9,400 Boe (ec zell cameteeonans 9,300 73 Oe | Nh Sse Ml eae caaatttas 6,700 58 Warthen* reports the same condition in a single case. Here the specific gravity was also very high (v. Limbeck finds that this is to be explained by the increase in the actual size of the cor- puscles). 1 Boston Medical and Surgical Journal, March 14th, 1895. 2 Virchow’s Archiv, vol. cxxxvi. PTOMAIN POISONING. 865 When there is any doubt as to diagnosis, the following test will settle it: Shake a small quantity of fresh-drawn blood into three times its volume of subacetate of lead. If the blood contains CO the mixture becomes of a fine red color; otherwise it turns choco- late-colored.’ 2. Da Costa (Med. News, March 2, 1895) reported a considerable diminution in hemoglobins of patients during etherization, especially anemic patients, but the investigations of Lerber? do not confirm this. Tansy Poisoning.—A single case examined at the Massachusetts General Hospital showed: Red cells, 4,600,000; white cells, 21,- 000; hemoglobin, 70 per cent. Corrosive Poisoning (Ammonia Fumes).—A patient whose throat was covered with a fibrinous pseudo-membrane in consequence of inhaling ammonia fumes showed a leucocytosis of 25,800. Red cells and hemoglobin normal. Another with vomiting and purging gave a count of 20,700 white cells. AMMONIA. . Per cent Age.| Sex.| Red cells. White hzemo- Remarks. cells. globin. verre ieee ee rioerar 27,000 | ...... Mouth and pneumonia. Opium Poisoning (Chronic).—The majority of cases of the mor- phine habit show normal blood, but in October, 1897, a man of twenty-six entered the Massachusetts General Hospital for the mor- phine habit who showed at entrance 36,000 leucocytes per cubic millimetre. Five days later the count was 21,200. A differential count of 500 leucocytes made on this day showed: Polymorpho- nuclear neutrophiles, 71 per cent; small lymphocytes, 12; large lymphocytes, 10; eosinophiles, 6; myelocytes, 1. At the time of leaving the hospital he still showed a leucocytosis of 16,400. He had no fever, and the physical examination was entirely nega- tive. Ptomain Poisoning (Rotten Fish).—A mother and her four chil- dren were brought to the Massachusetts General Hospital suffering ‘Rubner: Zeit. f. anal. Chemie, xxx., p. 112. 3 Inaug. Dissert., Basel, 1896 (see p. 109). 366 from the effects of decayed fish eaten that day. The blood showed the following: (1) mother: leucocytes, 21,600, of which 95.3 per cent were polymorphonuclear; (2) boy of seven years: leucocytes, 19,900; (3) boy of three years: leucocytes, 56,800, of which 92 per cent were polymorphonuclear; (4) girl of five years: leucocytes, 32,600; (5) girl of thirteen months: leucocytes, 55,400. The red cells and hemoglobin were normal. All the patients made prompt SPECIAL PATHOLOGY OF THE BLOOD. recoveries. CorrosrvE Porsonrne. CaRBOLIC ACID. Age. | Sex. | Redcells. | White cells. | ,aCosobin, Remarks. Re | at fo aaheawien 10,800 | ........ No signs, BB ol dara: |W Seuzaserale ts 15,200 ARSENIC. GE. ak) dae eanatas 11,600 ACUTE ALCOHOLISM. It has been shown experimentally that in animals made drunk with alcohol, there is an invasion of the blood and tissues by micro- organisms from the intestine. It may be that some of the counts here recorded are thus to be explained. TaBLe LX.—AcuTE ALCOHOLISM. Per cent Age.| Sex.| Redcells. | White cells. heemo- Remarks. globin. | Vakese le aselatel a 44,000 95 ' 32,000 8 2d. 20,000 ae 3d. 7 a ere ree 42,000 is Followed by delirium tremens. OOo ar ateeticvee ans 29,800 Autopsy. anes |) ee meteaeians tons 25,000 Delirium tremens. OO. |) it |) ama e sleo 23,900 B6 | Fe] vecevsse 15,900 Two weeks drinking hard; Temperature 102°; died. delirium tremens. OS: Ey || Bauer aie see 14,200 74 Temperature 101°. GRANULAR DEGENERATION OF RED CELLS PLATE A. IN LEAD POISONING. STAINED WITH WRIGHT'S MODIFICATION OF LEISCHMANN’S STAIN. (Microphotographs by Lewis A. Brown, Clinico-Pathological Laboratory, Mass. General Hospital. No. 5. No. 6, PLUMBISM. 367 Taste LX.—Acute ALconouism (Continued). Per cent Age. |Sex.| Red cells. | White cells. heemo- Remarks. globin. 42) M.j ........ 12,000 62 Temperature 101°; delirium tre- mens. A228, | oetene ee 12,600 Chronic case delirium tremens. AG Yc th sien tarecel 11,000 vel od Peale Bans 10,200 fs Delirium tremens. 32 | M. | 3,936,000 10,200 30 (2) AA | Moy cw ccc s 9,600 80 eee oaellk wadesttanyierd 8,100 29 | F. | 4,288,000 8,000 55 Delirium tremens. Ol | Me | ea eetseads 7,800 62 GO) Boo) sexewes ge 7,450 65 cdots il aitateor cates 7,000 its December 21st. 11,900 a December 26th. eae 6,800 6,400 AG, Delirium tremens. 32. Me | sescesss 5,700 68 Autopsy. Q8 | is | wasaiess 5,600 aa Delirium tremens. eae aa | weet eae 5,600 PLUMBISM. Among the deleterious effects produced by lead in the human body, anzemia is one of the most serious. It is of the type of ordi- nary symptomatic anzmias except in one particular to which atten- tion has recently been called by Grawitz, viz., spotting or stippling of the red cells with fine basophilic granules, which can be well seen in specimens fixed in absolute alcohol for a few minutes and stained with Loeffler blue, Goldhorn’s polychrome, methylene blue, or other basic dyes. These basophilic granules are often seen in various forms of very severe anemia, but in plumbism they appear even ahen the anemia is otherwise of a mild type. The following table exemplifies the degree of anemia ordinarily seen: TasLE LXI.—LEApD Porsonine. eat call d cells. White ene. Remarks. Age. | Sex. | Reacels: | ens. | gtobin. : on | ee | 4,500,000 | 23,400 50 Lead colic and headache. 2 | 2: | 3,800,000 | 22,800 | 48 3 16,800 Eighth day. gil las tenes | 22,700] 64 38 | °° |5 130,000 | 14,800! 59 at 368 SPECIAL PATHOLOGY OF THE BLOOD. TaBLE LXI.—LEAD Porsonine (Continued ). ; Per cent Age. Sex. Red cells. we heemo- Remarks. : globin. AQT) ety Pill sadreunaeos 14,600 December 28th. 11,400 February 2d. Polynuclear, 71.2 per cent. Lymphocytes, 24.6 = Eosinophiles, 4.0 Myelocytes, a2 - Ol Ol) eae || aan eles 12,600 72 44 8,888,000 | 11,600 38 Fits, colic, anemia. 35 8,700,000 | 10,000 50 Colic. 17 3,820,000 | 9,200 48 Chronic. 33 4,258,000 | 8,600 55 32 8,208,000 | 7,200 50 52 4,221,000 7,100 45 August 10th. Polynuclear, 72.4 per cent. Lymphocytes, 23.3 a Eosinophiles, 2.5 e Myelocytes, 1.8 a Megaloblasts, 1. Normoblasts, 1. 4,848,000 | 8,000 50 August 20th. Polynuclear, 71.4 per cent. Lymphocytes, 25.6 % Eosinophiles, 2.6 Myelocytes, 4 Normoblasts, 1. 33 4,000,000 ; 5,200 50 44 8,056,000 | 5,200 45 BO" | || ae | cayssepesstensa 4,500 SUNSTROKE AND HEAT EXHAUSTION. The leucocyte count may be either high or normal, according to conditions not well understood. SUNSTROKE. Per cent , Age. Red cells. | White cells. hheemo- Remarks. globin. DON oh ace soceeatetent 24,000 67 13,400 ie Two days later. BB. | ce sawenee 22,800 Temp., 107°. Died. AD | es Baa nes 21,000 Qe: |e vewesier 10,000 Temp., 110°, first day. 5,200 e Temp., 104°, fourth day. Died. Wii | or eon yaeas 10,000 95 Oh. h aaceytnatiie 10,000 BR) soa aig eves 9,800 62 SUNSTROKE AND HEAT EXHAUSTION. 369 Heat EXHAUSTION. Per cent Age. Red cells. | White cells. hemo- Remarks. globin. ay fl ainsaeates 24,000 80 Recovery. 62s |, siceaane 18,200 ~ Recovery. Temp., 98.8°. gts! Ul ietvceana cs 11,000 5 Recovery. Soe beau mated 9,000 9 Recovery. Temp., 98°. BA | sae reas 5,000 Recovery. Temp., 99°. ELectric SHOCK. Age. White cells. Q0' > pe eho exreiemeri wees eka meas Nev ne'ee se aSeawEia ee 8,900 PART VI. MALIGNANT DISEASE, BLOOD PARASITES, AND INTESTINAL PARASITES. CHAPTER X. MALIGNANT DISEASE. Tue Bioop as A WHOLE. 1. Tue specific gravity is reduced in most cases, running roughly parallel with the hemoglobin. 2. Coagulation is normal or slower than normal in uncomplicated cases. When sloughing and inflammation are present it may be rapid. 3. Fibrin is usually normal; an increase means inflammation in or around the tumor or an inflammatory complication. 4. Occasionally the resistance of the red cells is extraordinarily low. In one of my cases the ordinary manipulations of preparing specimens (either fresh or film) for examination invariably mangled the red cells beyond recognition, no matter how quickly and care- fully the technique was carried out. In the fresh specimen the red cells seemed to fuse into each other in clumps, their biconcavity lost. The plasma became turbid with hemoglobin despite every precaution. This was a case of cancer of the kidney with multiple hemor- rhage from various surfaces. I have never seen another case like this one, but in literature several such are mentioned. CANCER. fied Corpuscles. As in tuberculosis, we are frequently surprised to find but little diminution in the number of red cells. In all but very advanced CANCER. 371 cases this is the rule. It isachange of the individual red cells (pal- lor, loss of size, of weight, degenerative changes), rather than a re- duction of numbers. Nevertheless in the later cachetic stages of most cases of malig- nant disease, we do find a quantitative anemia, the counts often running as low as 2,500,000 and occasionally sinking as low as in pernicious anemia. Thus v. Limbeck records a case (complicated by repeated hemorrhages) with only 950,000 red cells per cubic millimetre. The lowest of my own cases was 1,457,000 per cubic millimetre. There seems to be no considerable difference between cancer and sarcoma as regards their effect on the red cells. The following table summarizes our cases: Tasie LXII., A.—Gastric CANCER. Red cells. Between 1,000,000 and 2,000,000 ............ .... 6 cases. . 2,000,000 “ 38,000,000................. 17 # 3,000,000 “ 4,000,000................. 37 & 4,000,000 “ 5,000,000................. 29 “ 5,000,000 “ 6,000,000 ................ 21 “ Over 6,000,000 ........ cece ccc ete eect eerie A Average, 4,090,000 + 114 cases. Nucleated red cells present in 11 cases out of 114 examined. Normo- blasts always in majority. A few megaloblasts in 3 cases. TaBLE LXII., B.—Gastric CANCER. Leucocytes per cubic millimetre. Between 8,000 and 4,000.................20000- 1 case. “ 4:000 “6,000 ei ences sictaidedee ea eee 4 cases. 5000" 6,000 sc4assansane sss dad eae dy « 6,000: © 7000 24 kadeas cesses ese 9 “ & 7,000) “8,000: 4 iccSawaeen dee eaani aes SS s 8,000 “ 9,000... cee cece cee eee 8 & ee 9,000. TO 000 a eieie vipegaiecciess oelarece salves ig) . 10,000: “12,000. a & = cs 5 Sarcoma of abdominal organs. Osteosarcoma (thigh). Differential count of 500 cells: Poly., 74 per cent ; small lymphocytes, 19; large lymphocytes, 6; eosinophiles, 1. Sarcoma of abdominal organs. Differential count of 800 cells: Poly., 84 per cent; lymphocytes, 15.5; eosinophiles, 5. Sarcoma of abdominal wall. al casei (esas 15}: fosce 1G) aseranasen 18) 30 Neck. One month later. Polynuclear, 89 per cent; lym- phocytes, 9.8 ; eosinophiles, 1.2, Neck. Autopsy. Caecum. Abdominal wall. December 2d. Adrenal. December 5th. December 16th. Small tumors are often without any effect on the blood (see Table LXVIII., B). According to v. Limbeck' this is oftener true than in cancer. 1 Loc. cit. 396 SPECIAL PATHOLOGY OF THE BLOOD. TaBLE LXVIIL, B.—Sarcoma witHout LevcocyTosis. Per Red White cent g| A& | 4] cells. cells. | heemo- Remarks. z Zz globin. |+ 1; 29 M. | 5,280,000 | 8,200 Sarcoma of testicle. 2) 37 F. | 4,980,000 9,000 Sarcoma of ovary. 3 ? M. | 4,946, 9,000 .| Osteosarcoma of shoulder. 4) 24 M. | 4,952,000 6,000 Small recurrent sarcoma of groin. 5] 46 .. | 5,890,000 | 6,100 Glands. Bl 4h | on | cece tens 7,600 7 Ovary. Ti 88°) gas [ies zeae BOO". Lecssiaess aw Cutaneous. 8) 47 4,288,000 5,600 65 Kidney operated. 9) 54 egpnecon 9,800 72 Kidney operated. TOK? BBY Hse [Sing avaiduvcess 5,100 65 Retroperitoneal. Polynuclear, 66 per cent: lym- ie G6; .| tures ¥ phocytes, 33.4 ; eosinophiles, .6. Reds good. 600 p.c. Hemoglobin.—Reinbach’s' 20 cases ranged between 23 and 75 per cent, averaging 52 per cent. Bierfreund? in 29 cases found variations between 40 and 75 per cent. Von Limbeck’s 2 cases had 28 and 48 per cent respectively. Rieder’s’ 4 cases showed at the beginning of treatment 29, 56, 57, and 65 per cent respectively, but in 1 case the hemoglobin went down gradually while under observation until it reached 6 per cent (!), the lowest point, Rieder says, that he has ever seen in any disease. Sadler’s* cases showed 33, 45, and 78 per cent. In the 16 cases of Table LX VIII. in which this point was noted, the average is 59 per cent. On the whole, the coloring matter seems to be more diminished than in most cases of cancer. Leucocytes.—The following tables, slightly modified from v. Limbeck, show the important points. No. Observer. Diagnosis. Count. Es ceaanenia. on nibh Hayem. Osteosarcoma. 11,250 chasers waver Gard Alexander. . 52,700 ieee ery aS caienaie * se 16,430 Bho oes he ea ieed laf . $ 16,275 ee a 17,050 Digdsirnhaeok ae ies . = 15,900 * ee 15,570 Ging eel dneceewalna. : 18,020 ! Loc. ett. 2 Loe. cit. 3 Loc. cit. 4 Loc. cit 397 SARCOMA. No. Observer. Diagnosis. Count. Ma aa ranaienyesie sae Alexander. Osteosarcoma. 10,950 se a 12,090 Se ocutaaaieaces Me “ 11,248 Des ire-sabwneead Rieder. “ 12,700 ne o 10,900 DQ ire serge net eaie i: sf 9,100 Li isere es iets he s ee 8,000 WR iik cea anamaneat v. Limbeck. f 32,000 # « 26,800 1D edict wabivewaee Reinbach. s 20,000 Whi ccagiees, anne - # 13,000 Wii edvenaiis ee Mass. General Hospital. a 21,000 16, sisis-aiwearanenwres “ ms e « 9,000 Average, 17,000 + No. Observer. Diagnosis, Count. Tis hie Rraiedionselle Hayem. Lymphosarcoma. 11,700 Dis Shc cSyinky saan sy Alexander. ss 19,910 Dleciesscarsicterecceeivce s 19,580 AS: oieiaie apumsaaaing ss “ 11,696 Ole ds samiemenees = e 11,470 Oued seek iwee ys i 10,540 Wekced Bie Me Dies ss v. Limbeck. ig 55, 100 Oy ed cesta cic eet inve * ba 38,000 De shai Suave ace sshd se ee 10,800 10k aeteaweas Sadler. ff 33, 248 Mh isittteerasie iets = ie 19,299 PDs sisters Waeetts * Ms 9,044 Average, 20,000 +- No. Observer. Diagnosis. Count. Dae tessa was Rieder. Melanosarcoma. 41,600 DO isiscense ae soeaceenians i 28,500 iatetallse-e Ghiaeuane ouetie # « 22,300 Aho sista ala aenrarere Reinbach. e 25,000 Deira bea ea vecdligvooa 7 # 8,000 Gi hese ceeds ans Mass. General Hospital. e 37,900 Tesiedrmee asses * « ‘ 18,000 Average, 25,100 + For other sarcomata, see Table LXVIII., A and B. On the whole, leucocytosis appears to be more constant and of greater extent in sarcoma than in cancer. 398 SPECIAL PATHOLOGY OF THE BLOOD. Qualitative Changes. 1. The increase of polymorphonuclear leucocytes which we find in most forms of leucocytosis is not always present in sarcoma’ and seems to be less frequent than in cancer (see Cases 5, 11, 14, Table LXVIII.). As in cancer, it may be present when no increase in the total leucocytes is to be found, and may be the only indication of any dis- ease in the organism. 2. A few cases are on record in which a large percentage of eosinophiles has been present. Reinbach found 48 per cent of eosinophiles in a case of sarcoma of the neck with sloughing and ulcerative endocarditis, the percent- age continuing over 40 for several weeks.* Autopsy showed sarco- matous nodules in the bone marrow. In another case, a tumor of the abdomen, the eosinophiles were 10.5 per cent, and in two others 8 per cent. A case of apparent sarcoma of the abdominal organs (no autopsy) at the Massachusetts General Hospital in January, 1896, had 12.4 per cent of eosinophiles. Such cases should certainly make us think of bone metastases, and Neusser speaks of osteosarcomata as being accompanied by eosinophilia, but the evidence is as yet fragmentary. 1 Palma (Deut. med. Woch., 1892) reports lymphocytosis in sarcoma. ? The full counts are as follows: April 4th, 1892. May 20th, 1892. Red cells............ 5,396, 000 Red cells............ 4,512,000 White cells.......... 120,000 (!) White cells.......... 52,000 Hemoglobin......... 60 per cent. Hemoglobin ........ 55 per cent. DIFFERENTIAL COUNTS. April 4th. May Ist. May 20th. May 26th. Per cent. Per cent. Per cent. Per cent. Poly. netti.. 00. aeedss 48 51 55 + 51+ Eosinophiles ..... is 48 46 42 44 + Lymphocytes 2.7 2.32 1.5 3.2 Myelocytes ........... 1 68 64 8 SARCOMA. 399 3. Myelocytes.—Reinbach’s case just described had a low per- centage of myelocytes. The following cases illustrate the same point: Case I. is a case of sarcomatosis in a man in whom sarcomatous nodules were distributed all over the internal organs and in the skin. A differential count of 700 white cells showed in his case: Per cent. Typical myelocytes (over 154) ........ cee cece eee eee 2 Small myelocytes (under 15z)..... 2... cee eee eee ee eee 5 Lymphocytes .cciecm soviasieuvtav es wireuied Saetsried 22 Polynuclear neutrophiles......... 0.0... cece eee eee eee 70 HOsinGpniles:< was sic-2sceyeaicecnaenonecaacaoeewrngy The autopsy showed no special lesions in the spleen, glands, or bone marrow, except those due to the sarcomatous nodules. Case IJ.—Sarcoma of the abdominal wall. A differential ‘count of 800 cells showed: Per cent. Polynuclear neutrophiles ....... 0... cece cece eee eee 84. LiVM PHOCY TES. ocdawaw-aeque-yereiicn vee SS WA ee Ra ES 10.5 Large lymphocy tS ssi isis sissies ecee setae as ve 5. Hosinophilessce..gnsasscavetessaee sae sae Peace adusie'es 2 Myclocytes nce cscctsedaeas adavates v4 stenvaweew serene 3 Case III. (No. 5, Table XLVIII., A).—Six hundred cells con- tained: Per cent. Polynuclear neutrophiles ....... 0... 0. e eee eee eee ee 71. NYDN PAOCVLES: sa .ceccalacn ae Vaasa ral eanied ule ine eos ora Maes ee 16.2 HosinOphilesiaicce aceistivndstea vas segouxpinass oes wehbe s 12.4 MYClOCYtOS cs ctsaeercess eee qa bee se 8a ce oaas Hoaeees A Summary of Blood Changes in Malignant Disease. 1. Small, slow-growing tumors and the early stages of all tumors may have no effect on the blood appreciable by our present methods of examination. 2. In advanced caseg the red corpuscles often become thin, light, and pale, and finally their number may be greatly decreased, the counts running sometimes as low as in pernicious anemia. In this respect, as in others, sarcomata seem to injure the blood more than cancers. 3. The color index is always below 1, but is rarely as low as we find it in severe chlorosis. 400 SPECIAL PATHOLOGY OF THE BLOOD. 4. Normoblasts and megaloblasts (the latter being in the minor- ity) may occur, the former even in the absence of severe anemia. Deformities in size and shape are common. 5. Leucocytosis is present in the cachectic end-stages of many cases, but is frequently absent in small tumors of slow growth and without metastases. The polymorphonuclear cells are often rela- tively increased. 6. Fibrin is not increased. Diagnostic Value. 1. When we are dealing with an obscure, deep-seated disease, if hemorrhage is excluded, the presence of persistent leucocytosis suggests suppuration or malignant disease (rather than tuberculosis or syphilis, for example), and excludes any simply functional or hysterical affection. The absence of leucocytosis, however, does not exclude malignant disease, though it makes suppuration very un- likely. 2. Between malignant disease and suppuration—if the other signs and symptoms do not decide—there may be nothing in the blood to decide. In decided pyeemia we may get pyogenic cocci from the blood by culture, but a negative result would not exclude the suppurating focus. The absence of any increase of fibrin in the blood speaks against suppuration, and therefore in favor of malignant disease; but the presence of increased fibrin network is not decisive either way, as it may be met with in connection with neoplasms, though more common in suppuration. 3. Between malignant disease and hemorrhage amarked anzmia favors the latter, provided the case is a recent one; for the anemia of malignant disease is comparatively slow to develop. The leuco- cytes give no help. 4, Between cancer and ulcer of the stomach, if there has been no recent hemorrhage, leucocytosis favors cancer; but its absence is of no weight either way. The hemoglobin is said to decrease steadily in cancer, while in ulcer it tends to return toward normal after the cessation of hemor- rhage. The presence and persistence of digestion leucocytosis speak against cancer, and its absence in favor of cancer. It must be remembered, however, that any variety of catarrh or dilatation SARCOMA. 401 (should such be present) can also prevent digestion leucocytosis, and that the latter is not invariably present even in health. 5. Between cancer of the liver or bile ducts on the one hand and simple gall-stone colic or gall-stone obstruction, the presence of leu- cocytosis favors cancer. As usual, however, its absence does not exclude cancer, and we must bear in mind that gall stones with. cho- langitis may raise the leucocyte count as much as cancer. Simple cysts or echinococeus cysts cause no leucocytosis, nor does syphilis of the liver. 6. The appearance in the blood of large numbers of eosinophiles, myelocytes, and nucleated corpuscles during the course of a malig- nant disease points to a bone metastasis. 7. When a leucocytosis which has disappeared after removal of a neoplasm reappears, we may expect recurrence of the growth shortly. 8. A steadily increasing leucocytosis in a case of malignant disease points to a rapidly growing tumor or to the occurrence of metastasis. 9. Between malignant disease and pernicious anemia, the diag- nosis rests on the following points: . I. Color index low in malignant, apt to be high in pernicious anemia. II. Leucocytes often increased in malignant, diminished in per- nicious anemia. III. Lymphocytes often decreased in malignant, increased in pernicious anemia. IV. Average size of red cells often decreased in malignant, and often increased in pernicious anemia. V. If nucleated red corpuscles are present the normoblasts are in a majority in malignant disease, and in a minority in pernicious an- emia. 10. The presence of leucocytosis is against the benignness of any tumor. 11. When no actual increase of leucocytes is present, an increased percentage of the polymorphonuclear variety among those present may have the same significance as a leucocytosis. 26 CHAPTER XI. BLOOD PARASITES. EXAMINATION FOR THE PLASMODIUM MALARI& AND ITS PrRopucts. I. Time for Hxamination.—It is often stated that the organism is most easily found during the chill. But this is not the writer’s experience. During a chill it is often difficult and sometimes im- possible to find the organisms. Eight hours before or after a chill is the most favorable time (Thayer), although parasites have been found as late as forty-eight hours after the last chill. During the chill many organisms retire to the internal organs. The number of organisms varies a great deal. In some cases they are present in every field of a one-twelfth immersion lens, while in others we may find only one after an hour or more of pa- tient seareh. In sume cases of coma Ewing had to search one and two hours before finding a single parasite. In the majority of the cases occurring near Boston, it needs but a few minutes’ search to find them if the blood be taken within twelve hours before or after a chill, and provided no quinine has been lately given. Occasion- ally in mild cases the organisms are very scanty; and it may be al- most impossible to find any. Theobald Smith agrees with Ewing that when the parasites are scarce, especially when they are of the small unpigmented form, a prolonged search through fresh blood has frequently proved negative, although a few minutes sufficed for the discovery of one or more minute parasites in the stained speci- men. The quartan and estivo-autumnal forms of malaria are so rare in New England that I shall not attempt to describe in detail the parasites found in them, but shall confine myself mostly to the parasites of common tertian and double tertian fevers with which I am personally familiar. Il. Method of Examination.—A slide of fresh blood is prepared as above described (pages 6-8) and examined with a one-twelfth immersion lens.’ Lower powers should not be used, although in 'In cold weather both slide and cover should be warmed before using. Indeed this is always well, as it makes the corpuscles spread better. BLOOD PARASITES. 403 skilful hands they are often sufficient. Portions of the slide in which the corpuscles do not overlie each other should be chosen for examination. As we pass the slide dtong beneath the lens it is well to be on the lookout for any specially large or specially pale corpus- ele. Such a one will catch the eye if we are on the watch for it, even though the slide is being passed along very rapidly, and all such should be carefully examined. : Another thing to watch for is anything black or dark brown. If the slide is not perfectly clean, or if the cover-glass has touched the skin in collecting the blood, there will often be black spots which make us pull up short and examine, only to find that they are bits of dirt. This loses time, and hence, as above noted, the impor- tance of care and cleanliness in the earlier stages of the process. Besides any strikingly pale or swollen corpuscle or any black dots, we should be on the lookout for any movements in the field. The movements of Miuller’s “blood-dust” (see page 60) are often mistaken by beginners for those of the malarial organism. Their greatly smaller size and extra corpuscular position serve to distin- guish them in most cases. I have sometimes thought I saw pig- ment in these bodies. If, as Stokes believes, the “blood-dust ” is derived from the leucocytes, it is possible that they might carry out with them some pigment ingested by the leucocyte. Flagellate bodies may be studied in fresh specimens, if possible, on a warm stage. Usually they appear only after the lapse of ten to twenty minutes from the larger tertian or crescentic estivo-au- tumnal organisms. The addition of a little water or salt solution may facilitate the escape of the parasite from the red cell and the formation of flagella. Ewing finds that the moist chamber may be secured in a Petri dish with tightly fitting vaselined cover. Wet blotting-paper placed in the dish furnishes the necessary moisture. Specimens spread on slides or covers may be kept moist for ten to twenty minutes in such dishes, and flagellation proceeds with moderate rapidity. A simple method is as follows: Cut an opening one-half by one inch in a piece of thick blotting-paper and moisten the paper in hot water. Spread two glass slides rather thickly with fresh blood, lay the blotting-paper on one slide, cover the cut opening by the other, specimen side down, and slip a rubber band about both. After fif- teen or twenty minutes the slides and paper may be separated and the two specimens dried. 404 SPECIAL PATHOLOGY OF THE BLOOD. Ill. The Malarial Organism.—(a) It practically is never to be seen outside the corpuscle. Most malarial organisms are to be found within the corpuscle, and only there.’ For those who have not examined many specimens of malarial blood it is a very difficult thing to find the organism at this stage of its growth, and the number of mistakes in diagnosis is very large. I always look with great suspicion on any report of malarial blood as containing on/y “hyaline forms.” ‘In the later stages, when the organism has become well pig- mented, there is nothing that at all resembles it, and those who have seen and watched it a few times can hardly mistake anything else for it. Not so with the so-called “hyaline” or youngest form of the organism. Personally I think the name “hyaline bodies” is responsible for a part of the mistakes. We are led to expect some- thing more shiny and refractile than the organism really is, and so are misled by the brilliant white circles to be found at the centre of many normal corpuscles under certain conditions of light and partial drying up. Time and again I have been asked to look at malarial organisms (always the “hyaline” forms), and found nothing more than one of these effects of light which can be found in any normal blood, if the conditions are right. There are certain marks by which we can exclude these artifacts from consideration : I. They are generally far too numerous to be malarial organisms. -One usually finds a dozen or more in a field which would be almost unheard of with the plasmodium malarie. II. They are generally in the centre of the corpuscle, while the young malarial organism is almost never at the centre. II. They are almost invariably round, the malarial organism being generally more irregular and branching. IV. They seem to increase and diminish in size as we focus up and down upon them, while the malarial organism only grows dim- mer or clearer. V. They are, as before mentioned, more brilliantly white and shiny than the malarial organism, which has often a faint tinge of yellow, although much paler than the surrounding corpuscle sub- stance. VI. Their edges are sharper, the malarial organism often fading off very gradually into the corpuscle color. 1Except degenerate forms, free flagelle, and spores at the moment of seg- mentation (rarely to be seen). Crescents and ovoid bodies are intercellular. PARASITES OF TERTIAN FEVER. PLATE V. (WRIGHT'S MODIFICATION OF LEISCHMANN’S STAIN.) Photographs by Wright & Brown, Clinico-Pathological Laboratory, Mass. General Hospital, Fic. 1.—The spotted cell on the right is an erythrocyte containing a young tertian organism and overlapped at its margin by a blood-plate. The dark mass overlying the cell at the ex- treme left is also a blood-plate. FIG. 2.—Two red cells showing granular degéneration. That on the right contains one, that on the left two, young tertian parasites. The chromatin bodies appear as rounded black spots. Fig. 3.—Young Tertian Parasite. Fic. 4.—Above, a tertian parasite about six hours old. Below, a blood-plate ~ overlying a red cell. Fic. 5.—Tertian Parasite about ten hours old. Fic. 6.—Red Cell considerably enlarged, In this and in the next figure the granular de- and containing two young tertian para- generation of the red cell is very marked. sites, BLOOD PARASITES. 405 VII. (a) Their movement is different. The malarial organism is not at all the only thing to be seen moving in the blood, as has sometimes been stated. The red corpuscles have the Brownian mo- tion, and as they begin to crenate often move very actively. But their motion is very different from that of the hyaline malarial organism, for the latter changes both its shape and its position in the corpuscle quite rapidly, while the motion of the light space in an ordinary red cell is a wavy undulation of the outlines back and forth without any considerable change of shape. (6) As soon as the organism gets any pigment (and there are very few times in the cycle of a malarial case when there are not some pigmented organisms present), the active rapid motion of the black pigment dots is unlike anything else seen in the blood, and when once recognized can never be forgotten or mistaken. It is only when the pigment has ceased moving (owing to the death of the organism) that the differentiation between dirt and malarial pigment becomes difficult. Sometimes it is really difficult to distinguish motionless pigment in a malarial organism from dirt even on careful scrutiny. The best way is to get a fresh slide when the pigment is in motion. To any one fairly familiar with the appearance of pigmented forms of malarial organisms, failure to find them in a case of mal- aria is due generally (1) to too thickly spread a layer of blood, the corpuscles overlying each other; (2) to not looking long enough; (3) to lack of proper light. (c) The next stage, that of segmentation, is less commonly seen than are those just mentioned, and is only to be satisfactorily ob- served by using a warm stage (vide supra, page 8) and spending con- siderable time on the watch for it. Around the central pigment mass we may sometimes see in ordinary specimens (without warm stage) the faint outlines of a group of small spherical, colorless bodies (vide Fig. 2, 9, Plate I.) which are the new generation of young organisms. Now we should expect that with the next step in the process we should find these young plasmodia free in the plasma or entering a fresh set of red corpuscles. But in the peripheral circulation this is rarely if ever observed. Thayer in his immense experience has never seen them. The next evidence we have of the organism is as a “hyaline ” body inside the corpuscle again. Almost all stages of the growth of the plasmodium which we 406 SPECIAL PATHOLOGY OF THE BLOOD. can watch in the blood drawn from the peripheral circulation take place within the corpuscle. It is true that as the pigmented organ- ism gets toward its full growth, and before the granules have begun to gather at the centre, we may find it very difficult to find any trace of corpuscle substance around the margin of the plasmodium. Sometimes we see a ring of non-pigmented glistening white sub- stance outside the moving black dots (see Fig. 2, 7, Plate I.) stand- ing out light against the durker plasma. ‘This I suppose to be the remains of the corpuscle. It is not described or pictured in the standard works on the subject. Occasionally we do find pigmented bodies wholly outside the corpuscle, either partly or fully grown. In the intracorpuscular forms the distinction between plasmodium and corpuscle substance is not, I think, so sharp and clear as one would be led to expect 4 Fic. 36.—Flagellate Malarial Organisms. (After Thayer.) from the plates in standard works. With average eyes and lenses the outline of the organism, as distinguished both from its pigment granules and the surrounding corpuscles, is not easy to see. It is the moving pigment granules that attract our notice. The youngest form of the tertian parasite seen in the red cell is identical in appearance with the spore of the parent rosette. Itisa compact spheroidal, or slightly oval, or irregular body, about 2 u in diameter. It shows an outer rim of basophilic protoplasm in- closing a single large nuclear body, which is achromic to methylene blue, but stains readily in hematoxylon or by Nocht’s method, and which is usually inclosed or accompanied by a clear achromatic sub- stance, termed by Gautier ‘the milky zone.” In the fresh condition these bodies are noticeably refractive, es- pecially the nucleus, change their position but rarely their shape, and are never pigmented. The young tertian ring: Within a few hours after the chill the parasite is usually found to have assumed a somewhat characteristic TERTIAN PARASITES ABOUT HALF GROWN AnD OccuPyING ENLARGED AND DEGENERATED ERYTHROCYTES. (STAINED AS IN Pate V.) IN No. 2 Two BLoop-PLATEs APPEAR AMONG THE CELLS. Photographs w Wright & Brown, from the Clinico-Pathological jaboratory, Mass, General Hosjital. PLATE 2 BS SU led COV 209) Fig. 3. Fia. 4, Vi. BLOOD PARASITES. 407 ring shape. These bodies measure from 3-4 » in diameter, and: there is not much increase in bulk for six or eight hours. The ter- tian ring is rarely as geometrical or delicate as the estivo-autumnal signet ring. The nuclear body of the tertian ring is its most char- acteristic feature, appearing as a rather large, achromatic, highly refractive body, after methylene blue, but staining intensely with hematoxylon and by Nocht’s method. Comparison of the Tertian and Aistivo-autumnal Rings. (1) According to Ewing, the nuclear body and the chromatin mass of the young tertian parasite are achromatic to methylene blue,. which densely stains the nucleus of the estivo-autumnal organism. (2) The shape and contour of the tertian ring is usually coarse and irregular, but the estivo-autumnal ring is geometrically circu- lar, more delicate, with extremely fine bow, and usually with a typical signet-like swelling. (3) One or two grains of pigment are almost invariably found in: the early tertian ring, but are with nearly equal constancy absent: from the estivo-autumnal signet ring. (4) The tertian ring is usually pigmented before the chromatin becomes subdivided, while the chromatin of the estivo-autumnal ring is always subdivided before the appearance of pigment. (5) The infected cell is usually swollen from the moment of in- fection by the tertian spore, and commonly shrunken when harbor- ing the estivo-autumnal ring. Large tertian vings: After a period of six to eight hours the ring is usually found to have developed an outgrowth which is actively amoeboid in the fresh condition and appears in stained specimens as a tongue-like protrusion or turban-shaped mass at- tached to one segment of the ring. The nuclear body meanwhile increases slightly in size, projecting into the ring, and the chroma- tin divides into several large granules. At this period occurs the greatest amceboid activity of the para- site, and in some severe infections the organism may be found fixed in the height of its amceboid excursions. There the ring persists,. but the body of the parasite is strung out into a number of slender threads with nodal thickenings. Tertian spheroidal bodies: During the second quarter of the cycle, the body and nucleus of the parasite develop rapidly in size, ameboid motion and figures gradually diminish, and pigment is 408 SPECIAL PATHOLOGY OF THE BLOOD. abundantly deposited in the form of dark brown or yellowish grains, showing in the fresh state active vibratory motion. The cell in- creases in size and its hemoglobin diminishes. Toward the end of twenty-four hours or possibly somewhat later, the parasite occupies three-fourths of the swollen cell, in the form of a spheroidal or elliptical, homogeneous body, the outer portion of which contains most of the pigment. Full-grown tertian parasite: The third quarter is occupied by the continued growth of the parasite in the form of a large homo- geneous, richly pigmented body, which finally occupies at least four- fifths of the swollen cell. Pre-segmenting bodies usually begin to appear in the blood eight to ten hours before the chill. The pigment is gathered in a re- duced number of coarse grains or spindles which lie in the body of the parasite, in a position determined by that of the new multiple nuclei. Tertian rosettes are usually seen in the circulation three or four hours before the chill, most abundantly just before the chill, rapidly disappearing after the chill. The earliest form of the estivo-autumnal parasite is often distin- guished from the tertian by the shrinkage of the cell, low refrac- tive index, and it is never pigmented. The wstivo-autumnal signet ring is a very characteristic shape assumed by the parasite at a very early period. It is noted that in some cases the rings fail to exhibit this thickening but remain of a uniform but very fine calibre throughout. Multiple infection with the young rings is very common; three parasites are often found in the same red cell, and occasionally four. The signet-ring forms frequently reach a diameter of 4 1; beyond this size, when persist- ing in the finger blood, the growth of the parasite produces an ir- regular body in which the outline of the ring becomes more or less obscure. The full development of the large signet rings appears to require about twenty-four hours. In the majority of cases the ring forms seen in the peripheral blood fail to show any trace of pig- ment. The later forms of the estivo-autumnal parasite are rather rarely seen in the peripheral circulation. The crescentic bodies: On the fourth to sixth days of any but initial paroxysms of the estivo-autumnal infection the peripheral blood may contain red cells infected by spheroidal, oval, elliptical, STAINED AS IN PLATES V. AND VI. Photographs by Wright & Brown, Clinico- Pathological aboratory, Masa, General Hospital, Fig. 1.—Above, on Right, a Half-grown Ter- tian Parasite. On left two blood-plates, one overlying a red cell. Fic. 3.—Same as Fig. 2. Fig. 5.—Same as Fig. 4. PLATE VII. Fic. 2.—Tertian Parasite, about forty hours old. The chromatin, in the form of tine granules, is within the open space in the upper left corner of the parasite. t ie (ves Py Fig. 4. — Well-developed Tertian Parasite. The chromatin appears as an irregular-shaped dark mass containing open spaces. Fic. 6.—Tertian Parasite just before seg- mentation. The chromatin (dark oval masses) is distributed throughout the parasite. The pigment (smaller dark ou is collected just to the left of the centre. BLOOD PARASITES. 409 or small crescentic bodies which represent the early forms of the sexual cycle of the parasite. The relation of these forms to the young ameeba is not clear. A remnant of hemoglobin surrounds the crescent on all sides. The membrane or thickened outer border of the red cell is closely applhed about the convex side of the cres- cent, while across the concavity it stretches loosely like a halter. In the centre of the crescent is a sharply marked, light-blue staining or a chromatic area of variable size, containing the chro- matin, and usually also the pigment. The long persistence of crescents in the blood and their resist- ance to quinine are matters of common clinical observation. Dr. J. H. Wright has kindly permitted the use of many of the accompanying photographs of the malarial parasites (see Plates V., VI, VIL, VIII., and IX.). Flagellate bodies: When blood containing crescents is allowed to stand in the air or under a cover-glass for a few moments some of the crescents slowly assume the spheroidal form, active vibratory oscillations of pigment granules begin, and soon, from one or more points, pseudopodia shoot out with active lashing movements. These flagella continue their movements for some time, changing their position actively, their shape slowly, while some may be seen to break off from the body and swim off through the plasma. Tertian flagellate bodies develop from the full-grown tertian par- asites in much the same way as from the crescents. Quartan para- sites develop flagellate bodies very similar in appearance to those of the estivo-autumnal type. Exactly why and under what conditions it shows or fails to show these appendages is not known.' They are about two or three times as long as ared corpuscle and one-sixth or one-eighth as wide. Sometimes there is pigment dotted along the flagellum itself, and then we can make it out more easily. Its distal end is especially apt to be pigmented, and by the help of this pigment we make out that it is bulbous, while similar swellings can sometimes be seen at other points along the flagellum (see Fig. 37). As the pigmented end is sometimes all that we can see of it, this gives rise to the appearance of a very small, actively locomotive pigmented body free among the corpuscles, and its course may be followed through several fields. *McCallum has recently offered interesting evidence that they are sexual organs. 410 SPECIAL PATHOLOGY OF THE BLOOD. When the flagella have ceased moving, their presence is generally detected, if at all, by an irregular line of pigment dots about 20 » long, which will be shown by careful focus- sing to be contained within a nearly transparent membrane. Very often we find a leuco- cyte in process of closing round the flagellated parasite. Man- son has lately succeeded in staining the flagelle, and the accompanying photographs are from his stained specimens. Pigmented leucocytes, con taining the whole or part o: malarial organisms or simply blocks or granules of black pigment, are usually to be foun in the blood near the time o the chill. The pigment is t be carefully distinguished fron the granules present in mos leucocytes, which in certau lights look quite dark even i unstained, dark enough to b mistaken for pigment by th untrained eye. Careful focus sing and changing the light wil easily determine which we ar dealing with, provided we ar familiar with the appearance of leucocytes in the fresh un stained blood. In certaj forms of the disease in whic the organisms themselves retip to the internal organs, th presence of pigmented lene Fig. 37.—Flagellate Malarial Organisms. 4 (After Manson’s photographs.) cytes may be the only evidene PLATE VIII. AESTIVO-AUTUMNAL PARASITES. (WRIGHT'S MODIFICATION OF LEISCHMANN’S STAIN. ) Photographs by Wright & Brown, Clinico-Pathological ratory, Mass. General Hospital. Fic. 1.—On the left a single young estivo-autumnal parasite. On the right two within a single cell. Chromatin appears in small, dark, rounded masses. ak FIG. 2.—Two estivo-autumnal parasites in one cell. In one the chromatin is divided. i. Fig. 3.—#stivo-autumnal parasite, somewhat more developed than in the preceding figure. ey ee Fig. 4.—Above, a blood-plate. Below, on the. Tight, a young eestivo-autumnal parasite. On the left a ‘‘ crescent.” BLOOD PARASITES. A41L of the disease to be found in the peripheral blood and is therefore of the greatest importance. Hitherto I have spoken of the appearance of the parasites in the fresh unstained blood, this being by far the simplest, easiest, and surest way of finding them and the only way of studying their development. In cases in which we cannot make a microscopical examination at the bedside, we can sometimes preserve the organ- ism alive between slide and cover-glass, until we can get it to the nearest microscope, even if this takes several hours. I have car- ried specimens in my handbag a whole morning and yet found the pigment of the malarial parasite in motion at the end of that time. Warm weather favors this. When it is necessary to keep. the specimen some time before examination, it is best to paint on the slide a ring of vaseline or any gummy substance, and allow the drop of blood to spread out inside this ring so that the margins of the cover-glass are glued to the slide by the oily substance and the entrance of air is prevented. The cedar oil ordinarily used for im- mersion lenses answers the purpose very well. Both slide and cover should be gently warmed before the drop of blood is spread Many physicians who cannot possibly carry a microscope about. with them can easily find room for a few slides and cover-glasses, and they may be of great service. ef When specimens have to be sent by mail, or for long distances,. or in cold weather, we have to fall back on dried specimens prepared as described on page 43, provided always that a bedside examina- tion is impossible. These can be stained by one of the following methods: I. Leave the specimen for half an hour or more in equal parts. of ether and absolute alcohol, dry them in the air, stain for from one-half to five minutes in a one-half-per-cent solution of eosin in sixty-per-cent alcohol, wash in water, dry and stain one-half to one minute in concentrated watery solution of methylene blue; wash again in water, dry in filter paper, and mount in Canada balsam. With this stain the nuclei of leucocytes and the malarial parasites are stained blue, while the red corpuscles are very pale yellow and almost transparent. This transparency of the red dises may be taken advantage of when the films either from accident or design are thick. The stained parasites can be recognized even if covered with a layer of red discs. After drying thoroughly in the air the malarial parasite stains. 412 SPECIAL PATHOLOGY OF THE BLOOD. best after fixation in ninety-five to ninety-seven per cent alcohol for fifteen to thirty minutes. The addition of ether to the alcohol . secures no advantage (Ewing). II. Thionin blue is a good malarial stain, especially for the young forms. Cover-glass films are to be fixed for one minute in a one-per-cent solution of formalin in ninety-per-cent alcohol, dried with filter paper, washed quickly in absolute alcohol, again dried with filter paper, and finally stained for thirty seconds in the following mixture, which should stand a week or more before it is used: Thionin (saturated sol. in 50-per-cent alcohol)....... 1 part. Carbolic-acid, 2 per CMe pcines sandwia se gatguiieces Gace 5 parts. Wash in water, dry in filter paper, and mount in balsam. Yet on the whole I have had better success with the eosin and methylene blue despite its difficulties. Modified Futcher and Lazcar method: “¥ix the specimens five minutes in ninety-five-per-cent alcohol to 100 c.c. of which has been added, just before using, 1 ¢.c. of formalin. Stain one to three minutes in the following mixture: Saturated alcoholic solution of thionin, 20 c.c.; 20-per-cent carbolic acid, 100 c.c. The fixing solution must be used fresh, and the staining fluid must be at least, one week old. The rings are then densely stained, and the speci- mens do not fade.” Ill. The ordinary Ehrlich triacid mixture with Hewes’ after- stain gives good results. The organism itself stains blue with this mixture and stands out against the yellow of the corpuscle, the pig- ment looking as it does in the live parasite. It is sometimes con- venient to use the same stain for the differential count and the mal- arial organism, as for instance when we have only one cover-glass preparation in a case of doubtful diagnosis. Fixing the specimen in alcohol and ether is here far better than heat; otherwise the technique is as above described under Triple Staining (page 44). If the organisms are fairly numerous and the technique is good we can find them by this method even in preparations months old. In general, however, it is very inferior to the examination of the live organism in the fresh blood, and gives many more chances for error. IV. Ewing states that he has never failed to secure a good re- sult by the following procedure: “1. To 1 ounce of polychrome methylene blue (Gribler) add 5 TERTIAN ORGANISMS. PLATE Ix. (AFTER WRIGHT & BROWN.) STAINED WITH EOSIN AND METHYLENE BLUE. Fig. 1.—Young Non-pigment- Fig. 2.—At the left, a young, pigmented ed Form (Tertian). tertian parasite. On the right, an adult tertian parasite. Rod - shaped pigment. The chromatin not stained. Fic. 3.—Two pigmented ter- Fig. 4.—An adult tertian parasite with central vacuole tian parasites in one cor- and rod-shaped pigment in a distorted red blood puscle. corpusele at the left of the figure. At the right of the figure an adult parasite with its pigment gathered together in clumps. This is a tertian parasite in the early stage of segmentation. The dark spots at the periphery of the parasite represent the remains of the red blood corpusele whieh it has invaded. Fic. 5.—An adult tertian parasite in the Fra. 6.--Completed segmentation of a tertian game stage as the one last mentioned, parasite. Each of the dark rounded bodies with its pigment collected in a more com- represents a young parasite. The pigment pact manner at its central part. The irreg- of the parasite from which they are derived ular dark zone at its periphery is the re- is shown, as well as the faint outlines of the mains of the red blood corpuscle in which red bloud corpuscle in which they are con- the parasite has developed. tained. BLOOD PARASITES. 413 drops of three-per-cent solution of acetic acid (U.S. P., thirty- three per cent). “2. Make a saturated one-per-cent watery solution of methylene blue, preferably Ehrlich’s (Gribler) or Koch’s, dissolving the dye by gentle heat. This solution improves with age, and should be at least one week old. “3. Make a one-per-cent watery solution of Gribler’s watery eosin. “The mixture is prepared as follows: “To 10 ¢.c. of water add +4 drops of eosin solution, 6 drops of neutralized polychrome blue, and 2 drops of one-per-cent methyl- ene blue, mixing well. The specimens, fixed in alcohol, or by heat, are immersed, specimen side down, for one to two hours, and will not overstain in twenty-four hours. The density of the blue stain may be varied to suit individual preferences. The above propor- tions need not be rigidly followed, but the polychrome solution should be accurately neutralized, and the staining mixture should be deep blue.” Goldhorn has recently succeeded in digesting methylene blue with saturated solution of lithium carbonate so as to develop in it a large proportion of the red chromatin-staining principle. This fluid, neutralized by acetic acid, not only stains the chromatin rap- idly (fifteen to sixty seconds), but demonstrates better than has yet been done early and extreme granular degeneration of the infected and other red cells. Goldhorn’s fluid, ready for use, can be obtained from New York dealers.' So much for technique. We often hear reports of fruitless search for the parasite in the blood of malarial patients, but the regularity with which they are found at all the larger hospitals and by all practised observers in this and other countries leaves no doubt that they are to be found in every case during some portion of the cycle. The practice of taking blood during a chill contributes, I believe, to the number of unsuc- cessful endeavors to find the organism; as mentioned above, this is the worst, not the best time to look for them. Too thick a layer of blood between slide and cover accounts for some failures, as I have found in personal experience. No doubt, in many cases in which we fail to find the organism in supposed malaria a faulty diagnosis is the reason. Many of the 1See Trans. New York Path. Soc., February, 1901. 414 SPECIAL PATHOLOGY OF THE BLOOD. cases in which latent malaria is supposed to have “come out” afte1 a surgical operation are exploded by the negative examination for parasites and the positive indications of pus-pocketing which are afforded by a marked leucocytosis (never present in simple malaria), and the fact of insufficient wound drainage is often disclosed in this way. Whenever we see the leucocytes increased we begin to doubt the existence of an uncomplicated malaria; if, furthermore, we see no signs of any pallor of the corpuscles we doubt the presence of malaria still more, as there is no more rapid deglobularizer than the malarial organism. How long after a chill the organisms may still be found in the peripheral blood is difficult to decide, but certainly they can be found any time within twenty-four hours after the last chill, unless quinine has been given, and sometimes even if it has been given. ’ OTHER CHANGES IN THE BuLoop. Red Corpuscles.—The following is from Thayer’s remarkable monograph : “A reduction in red corpuscles follows each paroxysm; these reductions are more marked after the early paroxysms than after those occurring later. When a certain degree of anemia has been reached the losses per paroxysm are much less. When the number of corpuscles is reduced to 2,000,000 or 1,000,000 there is little tendency toward a further fall; sometimes there may be slight rises in the curve between the paroxysms; often, however, the number of corpuscles remains stationary for weeks. “Tn pernicious cases the number of corpuscles may fall between paroxysms.” Kelsch has seen the count decrease to as small a number as 500,000 per cubic millimetre. The diminution is greater the longer the disease lasts and the more intense its manifestations are In Ewing’s Montauk series, there were “no less than nineteen cases in which the changes of the progressive pernicious type had been established in a period not longer than ten weeks.” There can be no doubt that the tendency of the estivo-autumnal parasite is to be massed in the bone marrow. The excessive de- mands on red-cell production render pernicious malaria an extremely favorable condition for this disturbance of the marrow and specific megaloblastic changes. PLATE X. Fig. 7.—A young tertian Fig. 8.—Same as Fig. 6. parasite and an adult parasite with a vacuole, in one red blood corpuscle. FIG. 9.—Crescentic form of the estivo-autumnal parasite in Fig. 10.—Same as Fig. 9. a red blood corpuscle, which is much distorted by it. The pigment is seen in the centre of the parasite in the form of rods. Fic. 11.—Ovoid form of the Fic. 12.—In the right of the figure is a crescentic parasite. gestivo - autumnal _para- In this photograph the blue-stained pdrasite is made to site distending a _ red appear darker than the eosin-stained red blood corpus- blood corpuscle. Aste) | reses'e eacn |) veges 4.2 3.0 6.1 | 86.6 2d. | capaceed | Gann 11.4 | 10.1 4.9 | 73.5 BO. | wecateee | aac 10.0 7.3 6.1 | 76.6 UIT | ievdyereigsiiers. |. Shacansliers 14.8 8.0 7.0 | 70.2 GUD |) Gsgce een. Is stateless 0.75) 5.0 | 18.8 | 76.0 BE | caw cece || Aawtenacs 3.1 9.5 8.6 | 78.8 Othe | servorets. |! ie eae 10.9 3.6 9.0 | 72.7 WOGHS hs Sas Sa wlangae (ls sey acaedn 11.2 | 18.2 | 14.2 | 56.4 18th | 3,300,000 | 17,000 13.1 9.4 9.3 | 68.2 Harlow Brooks’ examined the blood in one case, and found at the time of admission to the Bellevue Hospital (February 2d, 1900) 18,000 leucocytes, with 10 per cent of eosinophiles; on February 12th, 1900, 44 per cent of eosinophiles; thence a gteady increase up to 83 per cent, followed by a decline, until on March 14th 15 per cent of eosinophiles was present. Many of the granules wer smaller than those of normal eosinophiles, but there was no evi- dence of forms transitional between eosinophiles and neutrophiles. F. P. Kinnicutt’ reported a similar case, and H. C. Gordinier® mentions two, one presenting 77 per cent, the other 29.9 per cent of eosinophiles. 'Med. Record, May 19th, 1900. ? Practitioners’ Soc., February 2d, 1900. 3 Medical Record, October 20th, 1900. 440 SPECIAL PATHOLOGY OF THE BLOOD. Summary. From the total of counts in cases here assembled the constant presence of eosinophilia in trichinosis may safely be inferred. Diagnostic Value. The characteristic blood lesions change trichinosis from the position of a disease very difficult and uncertain of diagnosis (with- ‘out excision of a bit of muscle) to one whose recognition is usually easy. Cases formerly diagnosed as typhoid, muscular rheumatism, or neuritis now find their true interpretation. Other Intestinal Worms. Bicklers, working under Leichtenstern’s direction, has recorded the following data in cases affected with various more or less inof- fensive worms: I, ANGUILLULA INTESTINALIS. Per cent. BosinOphile sisi idles ean agd sdee ss xaweweds pa Sad 13.5 POLY DUGCIEATS -siacasavace 04 Sarda dinate wane Seblaeusins. baat a-aeoreniness 38.5 Lymphocytes and transitional..................00.08. 48 II. ANGUILLULA INTESTINALIS WITH ANKYLOSTOMA. Per cent. HOSIMO PHile ss seeds si ag siete Becek ew aeoneagg wave eaeeeaes 15 POLHUCIEATS iis cc nadine dade ese benGadewg Ganaews 58 Lymphocytes and transitionals.............. 0... ee eee 27 Il. Case I. Case II. Case III. Case IV. Oxyuris and Oxyuris. Oxyuris with | Oxyuris with ascarides. ascarides and |ascarides, trich- trichocephalus. | ocephalus and Tenia saginata Eosinophiles .......... 19 per ct. 16 per ct. 8 per ct. | 5.7 per ct. Polynuclears.......... 53 638“ 69“ 63.38 “ Lymphocytes and tran- Sitionals ............ 28 OC 21 * 23—~=CSS 31.0 “ IV. AscaRIDES (alone). Case I. Case II. Case III. Case IV. Eosinophiles........... 7.4 per ct. | 8.5 perct. | 9.8 perct. | 1.8 per ct. Polynuclears......... 55.0“ 55.0“ 50.0 “ Lymphocytes and tran- a sitionals ............ 37.6 26.5 “ 40.2 “ TRICHINOSIS. 441 The report of the Jenner Hospital at Berne (1890) includes the account of a case in which ascaris was present in large numbers. The blood showed but 2,480,000 red cells before the expulsion of the parasite’ by santonin; two weeks later the red cells were 4,200,000. V. Tania (Biicklers). Case I. Case II. Case III. Case IV. Case V. Tenia Tenia Tenia Tenia Teenia Solium. Saginata. Nana. Saginata. Saginata, Eosinophiles........ 8.2p.ct.| 5.5p.ct.| 7.0p.ct.| 5.0 p. ct. 10.0 p. ct. Polynuclears........ 49.4 “ |65.0 “ |420 “ Lymphocytes and transitionals...... 42.4 “ 1/295 “ |51.0 “ CHAPTER XIII. DISEASES OF THE SKIN. DERMATITIS HERPETIFORMIS. Accorpine to Leredde, who has written extensively on the con- dition of the blood in this disease, the following terms are in use to designate the same actual set of facts: Dermatitis herpétitormis; Dihring’s dermatosis; Polymorphous pruriginous dermatitis; Hydroa (Unna); Pemphigus vegetans (Neumann); Hallopeau’s infectious dermatosis; Herpes gestationis. In all of this he finds marked constant eosinophilia, averaging 16 per cent. At times the percentages may reach 25 or 30. My own experience includes three cases, one diagnosed as der- matitis herpetiformis, the others as hydroa estivale. The counts were as follows: Case I. Case II. Case III. Dermatitis herpe- | Hydroa estivale. Hydroa estivale. tiformis. Polynuclear neutrophiles..| 47 per cent 40.0 per cent 34 per cent Small lymphocytes. ....... 25. 8 42.4 “ 43 “6 % Large lymphocytes........ Bie * 86 “ & Ses Eosinophiles .............. DIQh te Bid eo 15. 8-8 My elocytes:s ones sctse ere es 1 Brown' reports the following figures in a case of dermatitis herpetiformis (twenty-seven years’ duration): June 12th, | June 17th, | June 25th, | June 30th, | Sept. 5th, 1899. 1899. 1899. 1899. 1899. Red. CONS oc cmeeweecees 5,128,000) ....... ] o...... 5,163,000! 5,808,000 White cells.............. TASO0O|) sot eae: ll passa sts 9,000 9.700 Per cent. | Percent. | Percent. Per cent. | Per cent. Polynuclear neut ........ 82.8 31.3 29.25 39.25 36.0 Lymphocytes............ 38.0 24.4 84.5 21.5 34.4 Eosinophiles............. 29.2 44.3(!)| 36.25 89.25 29.3 1 Soe. for Original Research, Conn., October 12th, 1899. PSORIASIS. 443, ERyTHEMA. Z White | Fer cent oan § Age. | Red cells. cells. anne : Remarks. DT] 295 YW anaes 19,700 SG First day. Temperature 102°; ery- thema nodosum and multiforme. 20,400 zie Second day. Temperature 103°. 12,900 ‘ss Sixth day. Temperature 98°. D1 IRL I aeaewallvern 18,400}. Temperature 104°. 6,800 5 Temperature 104°, third day. Eosino- philes not +. 3B) AS Ie sveced 11,400 65 Nodosum. Al AN eaee ness 8,200 ne Temperature 102°. Bl) 24> [sce evcsae 6,150 a Diff. 425 cells. Polynuclear, 69; lym- phocytes, 30; eosinophiles, 1. HERPES TONSURANS. Mark A. Brown’ records this blood count: White cells, 10,700; of these, there were eosinophiles, 25.2 per cent; polynuclears, 45.6 per cent; lymphocytes, 29.2 per cent. CHRONIC ECZEMA. Thomas R. Brown’ reports a case of chronic eczema, studied at the Johns Hopkins Hospital, in which three counts showed 22.6 per cent, 24 per cent, and 22.7 per cent. of eosinophiles. Zappert (oc. cit.) notes a similar case with 8,600 leucocytes per cubic millimetre, 9.9 per cent of which were eosinophiles (843 abso- lute). Bettmann records 45 per cent eosinophiles in a similar case. SCLERODERMA. Two cases in Zappert’s series showed: Per cent Leucocytes. eosinophiles. dL davai See va pais eee 16,690 9.4 (1,580 absolute) Dict Saute one aaa 9 000 1.7( 694 “ ) PSORIASIS. One of Zappert’s cases had 8,600 leucocytes, with 9.8 per cent of eosinophiles (850 absolute). 1In Conn. Lancet-Clinic, December 22d, 1900. * Jour. of Exp. Med., vol. iii., p. 320. 444 SPECIAL PATHOLOGY OF THE BLOOD. PEMPHIGUS. Zappert’s three cases showed: Cases Red cells. White cells. Per cent eosinophiles. Lindcaes scat 3,952,000 5,300 33.0 (1,750 absolute). D sii ha ayer’ eres 3,940,000 10,600 14.1 (1,500 absolute). De Santali se a wane 4,120,000 1,640 29.2 (4,800 absolute). LUPUS. Two cases (Zappert). Cases. Red cells. White cells. Per cent eosinophiles. 1, ces vapagdeus 3,224,000 9,200 12.2 (1,126 absolute). Oi Ses peed soc 4,250,000 9,450 7.3 ( 696 absolute). CHAPTER XIV. THE BLOOD IN INFANCY. I. All the signs by which sickness is shown in the blood of adults are exaggerated in children. Their blood is apparently more sensi- tive to the action of any morbid influence. Causes leading to but slight anzemia or leucocytosis in the adult, produce grave anemia and very marked leucocytosis in children. Into the reasons for this I shall not attempt to enter. The increased toxicity of their serum compared to that of adults, and the relatively recent establishment of the functions for producing and destroying blood have been sug- gested as explanation. Comparatively slight hemorrhages, gastro-intestinal or respira- tory disorders, which would not impoverish an adult’s blood may produce considerable anzemia in a young child. II. All forms of anzemia in infancy are apt to be associated with enlarged spleen. III. I have already alluded to the polycythemia and leucocyto- sis of the new-born, and the gradual fading out of these relative abnormalities as the child grows up. In judgments as to the pres- ence or absence of leucocytosis in infancy, these physiological varia- tions are too often lost sight of, especially as the proper leucocyte count for any given infant depends not simply on its age but on the backwardness or forwardness of its development. As with the fon- tanelles, the growth of the blood toward adult conditions may be retarded by congenital weakness (infantile atrophy, marasmus) or inherited disease (tuberculosis, syphilis) as well as by acquired sickness (rickets, cholera infantum). Under the influence of any of these drawbacks a sick child’s blood may be no further developed at three years than that of a healthy child of eighteen months. IV. When we remember that in early infancy the leucocytes ditfer from those of adults not only in number but in that the lym- phocytes are relatively more numerous (“lymphocytosis of infancy”), we shall understand that any influence like rickets or syphilis, which 446 SPECIAL PATHOLOGY OF THE BLOOD. retards development, will show lymphocytosis together with the increased leucocyte count. Qualitatively as well as quantitatively the blood reverts to a more infantile condition. V. This shows itself not merely in the leucocytes but in the red corpuscles. During the first days after birth the infant’s blood shows greater variations in size and shape than that of adults, as if the type were not yet quite fixed. The majority of authors also find a few normoblasts in the first few days of life. These are not invariably present, doubtless because in some children the blood at the time of birth is more developed than in others. Under pathological conditions the red cells revert to this earlier type, and deformed or nucleated corpuscles are plentiful. This is more marked than in anemia of the same grade occurring in adults. An anemia that shows but thirty nucleated erythrocytes per cubic millimetre in an adult might show ten times that number in a child. VI. As I said before, all blood changes are exaggerated in in- fancy. This includes such physiological changes as the digestion leucocytosis or that following cold bathing as well as pathological leucocytosis and anemia, and changes in the degree of dilution or concentration of the blood seem to be similarly exaggerated, as is seen, ¢.g., in the physiological variations in the specific gravity of the serum (Hock and Schlesinger’). VII. The hemoglobin, though relatively high at birth and for the first few weeks, is lower than that of adults during the rest of childhood. The high percentages of the earliest weeks are not due to a polycythemia, but to a genuine increase of hemoglobin in the individual cells (Schiff*), color indexes being often over 1. It is indispensable, therefore, that we should know the age and degree of development of a child before we can draw accurate infer- ences from its blood. In many of the cases reported in literature we are unable to judge whether the blood condition is pathological or not, because the age of the child is not given. For example, v. Limbeck * notes a case of acute gastritis reported by Fischl* as hav- ing an unusually high percentage of lymphocytes (59.4 per cent). But this is physiological in the first days of life, and may have been so in this case, the age not being given. 1 Hock and Schlesinger: Centralbl. f. klin. Med., 1891. * Schiff: Zeit. f. Heilk., vol. xi., 1890. %v. Limbeck: doe. eit., p. 873. +Fischl: Zeit. f. Heilkunde, 1892. THE ANAMIAS OF INFANCY. 447 Observations of this sort should always represent a comparison between the conditions present before and during the sickness in question. Bearing these general considerations in mind, we shall be better able to find our way among the complications and perplexities of the blood conditions in infancy. THE AN/EMIAS OF INFANCY. As above mentioned, anemic infants are apt to have enlarged spleens. This may be due either to the anemia or to some disease accompanying or underlying the anemia (e.g., rickets, syphilis). It seems more probable that the hypertrophy is not directly or ex- clusively dependent on the anemia, inasmuch as similar blood changes are found without splenic enlargement. By far the greater number of reported cases of severe infantile anemia are accompanied or caused by such diseases as rickets and hereditary syphilis, both of which may cause splenic hyperplasia even when no anemia is present. It seems probable that the anzmia and the enlargement of the spleen are alike symptomatic of an underlying disorder. 1. Some writers (e¢.g., Luzet’) divide the anzemias of infancy into two classes: those with splenic enlargement and those without it. Luzet considers that the former class is severer than the latter and more apt to show large numbers of nucleated red corpuscles than those with normal-sized spleens. This classification, however, does not always hold. We may have very severe anemia without splenic enlargement and splenic enlargement with slight anemia, and the presence or absence of numerous nucleated red corpuscles is governed by conditions other than the size of the spleen. 2. Another classification of children’s anzmias was proposed in 1892 by Monti and Berggriin (“Die chronische Animie im Kin- desalter,” Leipzig, 1892). They divided the cases into the mild and the grave, each group being subdivided into those with leucocytosis and those without it. +, § With leucocy tosis. | Mild= 7 Without lencocytosis. \ \ — § With leucocy tosis. [cure = | Without leucocytosis. They rightly discard the term “splenic anemia,” corresponding as it does to no single set of blood changes. The above classifica- 1Luzet: Diss., Paris, 1891. Secondary anemia of infancy= 448 SPECIAL PATHOLOGY OF THE BLOOD. tion puts pernicious anzemia, leukemia, and anemia infantum pseu- doleukemica (v. Jaksch) in a different category. (a) Mild cases of secondary anemia show no deformities in the shape or size of the red cells. The color index may or may not be low. The cases with leucocytosis are much more numerous than those without it and more apt to have a low color index; in other words, the loss of corpuscle substance is greater and the cases are approaching the imaginary boundary between “mild” and “grave.” (6) The grave cases have poikilocytosis, and of course a greater reduction of corpuscle substance. “ Chlorotic ” conditions, and most but not all those with enlarged spleen, come under this heading; also most of those due to heredi- tary syphilis, prolonged diarrhea, and rickets. In 1894 Monti’ gave the following classified lists of the com- monest antecedents of secondary anemia in infancy: Congenital, Syphilis, Malaria, etc. aue to... Tuberculosis, {1 the mother during pregnancy. ( From navel. After circumcision. A, Sent purpura, hemophilia, Werlhof’s disease, meleena. ( Inanition. Bad hygiene (lack of light, air, etc.) Post-febrile. Nephritis, diarrhcea, serous effusions. 2. Other causes. { Syphilis. Rickets. Suppuration. Diseases of liver, spleen, bone, or lymph glands. 2. Acquired... He points out that cases with leucocytosis are usually graver than those without it and may develop into pernicious anemia; also that the presence of leucocytosis does not point to malignant disease, suppuration, or any of the causes which usually account for it in adults. Grave cases with leucocytosis in infants under twelve months are apt to develop into the anemia infantum pseudoleukemica, or into true leukemia or pernicious anemia. On the whole, the division of Monti and Berggriin seems much better than that according to the particular causes, e.g., “rachitic anemia,” “syphilitic anemia,” etc., for there is no particular set 1 Wiener med. Woch., 1894. THE ANASMIAS OF INFANCY. 449 of blood changes that follows rickets, syphilis, or any other disease. In connection with various diseases of infancy, and particularly with those last named, we may have anemia of any grade of sever- ity, from that reducing the red cells to 4,000,000 down to cases with only 500,000 red cells per cubic millimetre or even less. The worse the case is the more likely is it to be accompanied by leucocytosis and the more numerous will be the nucleated red corpuscles, always more numerous here than in anemia of adults. In syphilis, hereditary or acquired, the red cells may fall below 1,000,000 and the leucocytes may rise as high as 58,000 (Loos). The hemoglobin may be proportionally diminished, or may be even lower than the percentage of red cells, so that a “chlorotic” condi- tion obtains. Such cases have been called chlorosis, but it seems better to con- fine this term to anemia of unknown origin and favorable course occurring in women soon after puberty, since obviously secondary cases may have similar blood. Rickets in a case observed by v. Jaksch caused a fall of the red cells to 750,000, and Luzet counted 1,590,000 in a similar case. The hemoglobin is usually low, but Hock and Schlesinger found 60 per cent with 2,300,000 red cells, a color index of 1.24. Leucocytosis may occur even when no anemiais present. Hock and Schlesinger found 45,000 leucocytes in a rachitie child of six- teen months, sound in other respects and not anemic. Acute gas- tritis causes at first only leucocytosis (with increased percentage of lymphocytes). If it becomes chronic the reduction of red cells is severe. Hayem found only 685,000 red cells per cubic millimetre in an infant of two months, though recovery eventually took place. In tuberculosis of the lungs and peritoneum in a child of seven, Monti and Berggriin counted 3,230,000 red and 17,200 white cells with 52 per cent of hemoglobin. Qualitative Changes. The exaggeration characteristic of all blood changes in infancy extends to the presence of nucleated red corpuscles, which in all forms of severe anemia are very numerous. What has been de- scribed above (page 91) as the typical megaloblast, a large pale- stained nucleus in a very large cell (see Plate IV.), is relatively rare in infancy. Thenuclei are almost always deeply stained what- ever their size, and apt to be small. Dividing nuclei are very com- 450 SPECIAL PATHOLOGY OF THE BLOOD. mon, both by karyolysis and karyokinesis. These changes are most often found in the anemias of the severest type and those which resemble leukemia (see below, page 456), but may occur in any marked secondary anemia. Polychromatophilic and “ degenera- tive” changes are very common in severe cases. The increased leucocyte count, so frequently found, is often made up of a majority of lymphocytes. This change, as above said, is not characteristic of rickets, syphilis, or any other cause of anz- mia, but it is to be regarded as a mark of the arrest of development or reversion to an earlier type of tissues brought about by various ‘diseases in early infancy. Sometimes the large lymphocytes and sometimes the small are in excess. A further qualitative change already alluded to (see above, page 118) is the occurrence of myelocytes. We have seen that small per- centages of these cells are not uncommonly seen in the anzmias of adults. Now this, like all other blood changes, is exaggerated in infancy. Myelocytes are more apt to appear and in greater numbers. Their presence is not characteristic of any one disease, but they are commonest in the severer types of secondary anzmia, such as those following syphilis and rickets. Their significance is about the same as that of normoblasts. At times, however, they are so numerous as to make us hesitate somewhat before we exclude splenic-myelo- genous leukemia. This brings us naturally to the discussion of the difficulty of distinguishing the different blood diseases in infancy, which naturally centres in the question of the existence and nature of the so-called “ANZMIA INFANTUM PSEUDOLEUKA2MICA.” Von Jaksch’s’ description of this disease (which he was the first to recognize) includes the following elements: 1. Grave anemia—e.g., 820,000 red cells per cubic millimetre in one case. 2. Extensive leucocytosis—e.g., 54,660 white cells per cubic millimetre, in the same case. 3. Great variations in the form, size, and staining of the white cells. 4. Deformed, degenerated, and nucleated red cells. Von Jaksch admits that none of these blood changes is charac- 1Von Jaksch: Wien. klin. Woch., 1889, Nos. 22, 238. ANAMIA INFANTUM PSEUDOLEUKAMICA. 451 teristic of the disease, but thinks that its title to the position of a distinct and separate disease rests upon clinical data, the more im- portant of which are: (1) A great enlargement of the spleen with- out any such accompanying enlargement of the /iver as is usually found in leukemia (the lymph glands are sometimes enlarged). (2) A relatively good prognosis. (3) Post mortem we find no positive evidence of leukemia. This description was given by v. Jaksch' in 1889. He stated the relation of white to red corpuscles as 1:12, 1:17, and 1:20 in the cases seen by him. Later he reported three cases in one of which the white cells numbered 114,150, and the red 1,380,000. The differential counts are not carefully given. Almost at the same time Hayem’ reported a similar case, and noted the abundance of nucleated red corpuscles many of which were undergoing mitosis. This was verified by Luzet*® in May, 1891 (dreh. gén. de Méd.), who reported two cases. His descrip- tion of the disease differs considerably from that of v. Jaksch. He finds no greater difference between liver and spleen than often exists in true leukemia. The course of the disease, though sometimes chronic, usually ends in death. The leucocytosis in Luzet’s cases was less marked than in those of v. Jaksch and not greater than that occurring in many anemias of children. He dwells particu- larly on the large number of nucleated red cells, and the frequency of mitosis, and considers this the most important diagnostic point. Although Luzet continues to use the name suggested by v. Jaksch, he describes the disease so differently that it is difficult to see why the same title should be given to it. He agrees with v. Jaksch in thinking that it is not simply a severe secondary anemia due to syphilis, rickets, tuberculosis, or infectious disease. Somewhat similar cases had already been described by various Italian writers (e.g., Fede) under the title of “ Infective Splenic Anemia of Infants.” Among others who have written on the subject are Baginsky,* Senator,®.Fischl,* Andeoud,’ Monti and Berggriin,® Felsenthal,° 1Von Jaksch : Wien. klin. Woch., 1889, Nos. 22, 23. ?Hayem: Gaz. des Hépitaux, 1889, No. 30. > Luzet: Diss., Paris, 1891. 4Baginsky: Arch. f. Kinderheilk., 1892, vol. xiii. 5Senator: Berlin. klin. Woch., 1892. 6 Fischl: loc. ett. 7 Andeoud: Rev. méd. de la Suisse rom., 1894, p. 507. Monti and Berggriin: loc. cit. *Felsenthal: loc. ett. 452 SPECIAL PATHOLOGY OF THE BLOOD. Raudnitz,’ Epstein,? Alt and Weiss,“ Hock and Schlesinger,’ Crocq,* and Rotch.° The majority of these writers report very little as to the differ- ential counts of white corpuscles. An increased percentage of the polymorphonuclear forms is mentioned by many, but Rotch in a case with 1,311,250 red cells and 116,500 white cells found only 16 per cent of the polymorphonuclear variety with 46 per cent of small lymphocytes, 34 per cent of large lymphocytes, and 4 per cent. eosinophiles. A second case had only 14 per cent of polymorpho- nuclear cells and 84 per cent of lymphocytes (large and small). Von Jaksch noted the lack of any relative increase of .eosino- philes, supposing this to be a means of distinguishing his cases from true leukemia. lLuzet, on the other hand, found eosinophiles nu- merous. (This of course has no weight for or against leukemia.) Klein (doc. cit.) noted the occurrence of myelocytes in small number. The discrepancy of these different reports is suggestive. The chief importance of the heterogeneous group of cases which have received the name of anemia infantum pseudoleukemica seems to me to be as a proof of the difficulty of distinguishing the various blood diseases in infancy. Among the cases reported under this name are some which might be any one of the following list: Pernicious anemia, second- ary anzemia with leucocytosis, Hodgkin’s disease, lymphatic leuke- mia, and probably splenic-myelogenous leukemia. (a) Most of the few reported cases of pernicious anemia in infancy have shown moderate leucocytosis (as compared with adult. blood), a fact which deprives us of one of the means of distinguish- ing the disease from secondary anemia. The reports as to nucleated corpuscles very rarely separate normoblasts from megaloblasts, and. we have no way, therefore, of being sure on this important point. The high color index and large diameter of the red cells are occa- sionally seen in other anzemias of infancy and are not always present in pernicious cases. The great fatality of all kinds of anemia in 1Raudnitz: Prag. med. Woch., 1894, p. 6. ? Epstein: Prag. med. Woch., 1894, p. 6. *Alt and Weiss: Centralb. f. med. Wissenschaft., 1892. 4Hock and Schlesinger: loc. cit. ’Crocq: “Etude sur l’Adénie,” etc., Brussels, 1819 (Lamartin). ®Rotch: Pediatrics, 1895, p. 361. ANAMIA INFANTUM PSEUDOLEUKAMICA. 453 infancy prevents our calling a case pernicious because of a fatal ter- mination. Enlargements of the liver and spleen occur in many cases of each type of infantile anemia, and occasionally in pernicious anemia of adults. They do not, therefore, exclude pernicious ane- mia in infancy. Bearing these facts in mind, it is evident that some of Luzet’s cases of “anemia infantum pseudoleukemica ” may have been per- nicious anemia. Von Jaksch’s own cases may have been either (a) Hodgkin’s disease with leucocytosis, (6) grave secondary anemia with leucocytosis (Monti and Berggriin), or (c) leukemia. (a) Hodgkin’s disease, which v. Limbeck finds to be very com- mon in infancy, may affect the liver and spleen and not the exter- nal lymph glands, and may be accompanied by anzmia and leuco- eytosis such as v. Jaksch describes. Epstein considers that this is the case, and denies the existence of any such disease as the anemia infantum pseudoleukemica. (6) As any anemia secondary to rickets or syphilis may have enlarged spleen and liver and marked leucocytosis, we cannot tell from v. Jaksch’s description that we are not dealing in his cases with secondary anemia. (ec) Since v. Jaksch does not give any accurate differential count of the leucocytes, there may have been large numbers of myelocytes in his cases for all we know, or an overwhelming percentage of lymphocytes, é.e., either type of leukemia. One of the cases reported by Rotch as ‘anemia infantum pseudoleukemica” had 80 per cent of lymphocytes in a leucocyte count of 116,500, the ratio of white to red cells being 1: 11, and the nucleated corpuscles abundant. The external lymph glands as well as the liver and spleen were enlarged. How such a case is to be distinguished from lymphatic leukemia without autopsy I cannot see. Large numbers of nucleated corpuscles with mitoses (present in this case) are to be found in any anemia of infancy in which the red cells, as in this case, have sunk as low as 1,311,500, and there- fore do not exclude leukemia. Von Jaksch protests that his cases are not secondary to rickets or any other disease, but Fischl’ in a careful study of all the pub- lished cases finds that, out of a total of eighteen cases, sixteen had severe rickets and two hereditary syphilis. The writings of Raudnitz, Ebstein, Felsenthal, Fischl, and v. 1 Fischl: Zeit. f. Heilkunde, 1892. 454 SPECIAL PATHOLOGY OF THE BLOOD. Limbeck, which deny the separate existence of the anemia infan- tum pseudoleukemica, are convincing to me, and are reinforced by the few cases of bad anzemia in children which I have seen. We must distribute the cases of anemia with leucocytosis and large spleen under pernicious anemia, secondary anzmia, and leukemia. But our problem is not yet nearly solved. All we have gained is the belief that v. Jaksch’s new disease does not help us to classify these doubtful cases. The difficulty is still very great. The fol- lowing cases reported by Dr. Vickery in the Medical News for De- cember, 1897, illustrate this: Casr I.—A male child of sixteen months with symptoms of grave anemia, greatly enlarged spleen and slightly enlarged liver, showed the following figures: Red cells, 2,500,000; white cells, 22,000. Differential count of 500 cells showed: Lymphocytes, 53.8 per cent (46.2 of the smaller type); polymorphonuclear cells, 29.4 per cent; eosinophiles, 6.2 per cent; myelocytes, 10 per cent. While counting these, 147 nucleated red corpuscles were seen, of which 21 were normoblasts, 50 megaloblasts, and 47 microblasts; 6 showed mitosis in their nuclei. The child died shortly after without any complication or inter- current disease. No autopsy. No evidence of rickets or syphilis or other previous disease. Case IJ.—Young infant with enlarged external lymph glands and very large spleen. July 14th, 1897—Red cells, 4,300,000; white cells, 31,000; hemoglobin, 60 per cent; polymorphonuclear neutrophiles, 57.5 per cent; small lymphocytes, 26 per cent; large lymphocytes, 15 per cent; eosinophiles, 0.5 per cent; myelocytes, 1 per cent. One or two nucleated red corpuscles in every field. Out of 100 of them 89 were large and 11 small. Many showed mitosis. Poly- chromatophilic forms numerous. July 19th—Seventeen megalo- blasts seen while counting 1,000 white cells. Blood is otherwise about the same. The case was lost sight of and not traced. Now I see no reason for supposing these cases to represent a new type of disease, and yet I cannot feel perfectly safe in classifying them as primary anemia, secondary anemia, or leukemia. (a) Primary or pernicious anemia should have a lower count of red cells. The percentage of myelocytes in the first case (10 per cent) is higher than in any other case of pernicious anemia on record, though in one adult case with autopsy I found 9.2 per cent with a leucocytosis of 12,500, or 1,150 myelocytes per cubie milli- metre, against 2,200 per cubic millimetre in this case. (6) It is hard to call an anzemia secondary which kills with no ANAMIA INFANTUM PSEUDOLEUKAMICA. 455 complications and when there is no evidence of any disease to which it can be secondary. (c) For splenic myelogenous leukemia the total leucocyte count and the percentage of myelocytes are very small in either case. Still the leucocyte count may drop very low in leukemia even with- out any inflammatory complication. Such a case is reported by Osler, in which the leucocytes fell to 7,500, of which only 300, or four per cent, were myelocytes. Hayem (loc. cit., page 864) in a ten-months old child counted 2,712,500 red and 33,000 white cells, almost the same figures as in the case just quoted. [Hayem unfortunately gives no differential count, but apparently considers the case leukemic because of the enormous number of nucleated red cells, many with mitoses. | Morse’s case of leukzmia in infancy had 2,900,000 red and 48,000 white cells. Twenty-one and four-tenths per cent of the leucocytes, or about 10,000, were myelocytes. The same abun- dance of nucleated red cells (some with mitoses) were here present as in Hayem’s case, so that there is evidently nothing peculiar in their presence in the disease described by v. Jaksch, as Luzet sup- posed. These cases show that leukemia may at certain periods present just such a blood picture as was present in the above-quoted case, and that the number of leucocytes in the leukemia of infants may be no greater than that in any anemia with the leucocytosis so com- mon in children. It seems to me the most natural conclusion to be deduced from these facts is that we meet with cases in infancy which wre appar- ently intermediate between leuk@mia and pernicious anemia. Ihave pointed out elsewhere that there are many points of resemblance between the two diseases. The case of leukemia reported by Osler showed at one period—the period of remission—a fall in the num- ber of leucocytes and in the percentage of myelocytes till the blood was practically that of pernicious anemia. Dr. Rotch’s case (above quoted) is another in which the diagno- sis seems to lie somewhere intermediate between the two diseases, anemia and leukemia. The case which I have quoted above seems to me on the whole nearer to the type of pernicious anemia than of leukemia, and Dr. Rotch’s nearer to the latter than to the former; but each is really intermediate, so far as the blood goes, between the two diseases. I 456 SPECIAL PATHOLOGY OF THE BLOOD. have no intention of suggesting that the organic lesions in these cases are intermediate between leukemia and pernicious anzmia. It is simply the blood that is so. Engel’s case, reported in Virchow’s Archiv, vol. 135, suggests the same thing. He calls the case one of “pseudo-pernicious anw- mia.” Myelocytes were abundant. Polymorphous Condition. This illustrates that “polymorphous” condition of the blood which v. Jaksch supposed to be characteristic of the anemia infan- tum pseudoleukemica. The same thing was very marked in all the bad cases of anemia which I have seen, including the case above mentioned, and a case of true leukemia in a girlof eight. The im- pression one gets from the field of a stained specimen is that no two white corpuscles are alike. Every species is subdivided into several sub-varieties and all stages of degeneration are to be seen in each variety. But this is characteristic of any very severe infantile ane- mia and not of any single type. LEUKAMIA. In Morse’s careful article of August, 1894 (Boston Med. and Surg. Journal), twenty cases of leukemia in infancy are collected. As he rightly says, probably most of these cases were not genuine. Only one of them includes a differential count, and this is in a lym- phatic case. Morse’s is the only one of the splenic-myelogenous type on record in which the diagnosis is made reasonably certain by a color analysis. Fischl in 1892 said that there was no case on record with a ditferential count. A case was seen in 1890 by Dr. F. C. Shattuck, which was ap- parently acute, the symptoms appearing only six weeks before death. Cover-glass preparations examined by W. 8. Thayer showed a ratio of about 1 white to 20 red cells. The differential count’ showed: Small lymphocytes, 97.9 per cent; large lymphocytes, .7 per cent; polynuclear cells, 1.4 per cent; eosinophiles, .08 per cent. The other case reported by Morse has been mentioned above. Charon and Giratea’ have recently reported a case in a child of 1Reported by Thayer in the Boston Medical and Surgical Journal, 1893, vol. cxxviii., p. 183. ? Bull. d. Soc. Roy. d. Sciences Méd., etc., Bruxelles, 1897, No. 7. LEUKAEMIA. 457 eight with 880,000 red cells, 305,000 white cells, and 39 per cent of hemoglobin. It was apparently of the myelocyte type. E. Miller thinks that there are about five other (German) cases on record, all of acute leukemia and all with a similar blood count, though in some the large lymphocytes (without neutrophilic gran- ules) have been described as “myelocytes.” Miller' has lately reported with great care three cases of leukee- mia, all of them in boys four years old—all apparently acute, all of the gastro-intestinal type—i.e., the glands and follicles through- out the whole length of the alimentary tract being the chief seats of infiltration, though the liver and spleen were also enlarged. The counts were as follows: Case I. : Cass II. Case III. ue May 1st.) May 2d.| May 3d. Red cells..........08- 1,508,000} 1,684,000} 1,362,000) 1,232,000 2,290,000 1,308,000 White cells. .......... 109,500 93,800 46, 6,800 206,000 420,000 Hemoglobin......... 40% eta Death. 25% Polymorphonuclear neutrophiles ....... 2% Many. 1% it Small lymphocytes}..| 85% (8-10 » diameter). Few. 15% 2: Large lymphocytes .. 13% Few. 84%, 97.38 Eosinophiles .......1-| sv eveeecucsececees Many. apsteis -01 Normoblasts.......... Few. Two normo-/Seven seen in Megaloblasts......... Few. blasts seen in} counting 1,118 cou nting| leucocytes, 1,135 leu- cocytes. 1 Jahrbuch fiir Kinderheilk., 1896, vol. xliii. * All with large pale nuclei. Pea Cb EXAMINATION OF THE SERUM. CHAPTER XV. THE CLUMP REACTION. GENERAL DESCRIPTION. ALTHOUGH this phenomenon is to be obtained in various infec- tions, natural as well as experimental, and with various body fluids, I shall describe as a typical case of it the reaction which may take place when the serum of a patient ill with typhoid fever is added in certain proportions (vide infiu) to a young bouillon culture of well- certified and virulent typhoid bacilli. In a drop of such a mix- ture, examined between slide and cover-glass' with a magnification of 300 diameters or more, we notice, at once or within thirty min- utes, a marked slowing of the progressive movements of the bacilli or an unequal distribution of them in the different parts of the preparation. Whichever of these changes occurs first, the slowing of locomotion or the tendency to grouping, the other soon follows, and then both processes go on together, as admirably described by Biggs and Park ? “Some of the bacilli soon cease all progressive movement, and it will be seen that they are gathering together in small groups of two or more, the individual bacilli being still somewhat separated from each other. Gradually they close up the spaces between them, and clumps are formed. According to the completeness of the reaction, either all the bacilli may finally become clumped and immobilized or only a small portion of them, the rest remaining 'Hanging-drop preparations are often recommended, but a simple slide and cover-glass are as good for the purposes of this reaction. 2? Amcrican Journal of the Medical Sciences, March, 189%. THE CLUMP REACTION. 459 freely motile, and even those clumped may appear to be struggling for freedom. With blood containing a large amount of the agglu- tinating substances all gradations in the intensity of the reaction may be observed, from those shown in a marked and immediate reaction to those appearing in a late and indefinite one, by simply Fig. 50.—Partial Reaction. Fic. 51.—Typical Clumping. varying the proportion of blood added to the culture fluid” (see Figs. 49, 50, and 51). The process may go on gradually and be much more distinct at. the end of half an hour. The groups or clumps above described constitute the important part of the reaction for diagnostic purposes. Of the loss of motil- ity more will be said later. 460 SPECIAL PATHOLOGY OF THE BLOOD. TECHNIQUE OF THE CLUMP REACTION IN TYPHOID FEVER. Our account of the methods of obtaining the clump reaction may be divided into the following parts: 1. The body fluids to be used and the methods of obtaining them. 2. The cultures. 3. Dilution and the time limit. 1. THe Bopy Fuiurps to se UseEp. Experiments have proved that the reaction can be obtained with the following fluids: (a) The whole blood, fluid or dried. (5) The plasma and serum, fluid or dried. (c) Also blister fluid, the fluid contents of normal serous cavi- ties, breast milk, pus, tears, and other body fluids. Of all these fluids, the blood, or the serum, fresh or dried blis- ters are the only ones used in clinical work. 1. Use of the Whole Blood— Fluid. The advantages of this method are (a) its quickness, and (4) the small amount of blood (one drop) sufficient for the test. I have used this method in most of my cases and always found it satisfactory and convenient. Procedure.—Suck up some water with a medicine-dropper and expel ten drops of it into a watch-glass. Then empty and dry the dropper, draw up from the watch-glass the ten drops just expelled, and mark with a file on the side of the dropper the point up to which the ten-drop column extends. Mark also the point to which one drop (expelled and then sucked up again as before) will rise. Ten drops of the bouillon culture of the bacilli to be used are then expelled into each of several small test-tubes, and one of these tubes is carried to the bedside. After pricking the ear as if for blood examination’ (see page 7), put the end of the medicine-drop- per into the blood drop, and carefully draw back the rubber bulb (which has been previously pushed down over the glass part of the dropper) until the blood rises to the mark for one drop. Wipe from the outside of the dropper any blood that may adhere there 1 Squeezing and milking the ear are of no harm in this procedure and en- able us to get on with a trifling and painless puncture. THE CLUMP REACTION. 461 and then expel the drop into one of the little test-tubes containing the ten drops of bouillon culture. In this way blood can be taken for examination from a dozen patients in as many minutes. 2. Whole Blood—Dried. The advantages of the method are (a) the ease and quickness with which the blood can be obtained, (/) the convenience for trans- portation by mail, and (c) that it does not deteriorate or become contaminated by bacterial growth, as specimens of fluid blood or serum are so apt to do. Its clumping power is fully equal to that. of the serum in most cases.* Procedure.—The blood should be dried either upon a glass slide or on a piece of glazed paper or card. Any absorbent substance is. less available. Glass is easier to sterilize than paper. Several large drops should be placed in different parts of the glass or paper and thoroughly dried. If paper has been used, we cut out the dried blood drop with a pair of scissors, keeping close to the blood all round, and drop it into a test-tube containing one or two drops of water, in which with . some sharp-pointed instrument we mix the dried blood, freeing it as well as possible from the paper. To the liquid so obtained add eight or nine drops of the bouillon culture of bacilli and proceed in the ordinary way. Or we may drop the fragment of paper holding the blood directly into ten drops of bouillon culture—using the bouillon itself to soak off the blood from the paper.’ The Fluid Serum. The ear is pricked in the ordinary way and about twenty drops are forced out by strong squeezing. The blood is received in a small (preferably two-inch) test-tube. The blood when collected may be at once centrifugalized, and the plasma used for the test, or we may wait till clotting occurs 1 Widal and Delépine think the fluid serum is slightly more powerful than the dried blood. Johnson admits that in one-tenth of the cases the serum is the more powerful. I have obtained reactions with the dried blood in only seven-eighths of the cases in which I got them with the fluid serum. 2?Some observers gather the blood on a bit of tinfoil and later crack it off, and after weighing it can make exact dilutions. Or we may soak blood into bits of filter paper of standard size and porosity and thus acquire a known amount as a basis for exact dilutions. 462 SPECIAL PATHOLOGY OF THE BLOOD. and use the serum. When blood is collected in test-tubes, it is. convenient to free the edges of the clot from the tube all round with some sharp instrument, so that the serum may not be pinned down underneath the clot, as it often is. If this is done, a drop of serum can be had within two or three minutes, and is then mixed with ten drops of bouillon culture, as above described, and examined at once between slide and cover-glass. (Dried serum can be used in the same way as dried blood, but has no special advantages and has not been frequently employed by any observer.) 2. Tue Cuttures oF TypHoip Baciuui To BE UsEpD. 1. The stock cultures grow best on agar at room temperature. 2. Ordinary peptone bouillon, free from sediment, is the best medium for the test culture. It should be just on the verge of lit- mus acidity, giving no blue to the red paper and requiring 3.5 per cent of normal alkali to render it neutral to phenolphthalein. 3. The cultures should be young—that is, the transplantation to bouillon should have taken place not more than from twelve to twenty-four hours before the culture is used. 4, The virulence and motility of the culture are very important. Most observers agree that the more virulent the culture the more readily and characteristically it is clumped by typhoid serum. Biggs and Park noticed that one culture of peculiarly great viru- lence recently received from Pfeiffer of Berlin worked much better in their cases than any other of the cultures used. Cultures fresh from an autopsy usually show furious motility, the bacilli darting about like a swarm of insects, but after repeated transplantations and long sojourn in the thermostat a good deal of this motility is gradually lost. Cultures kept at room temperature preserve their motility for much longer periods. « For those who have no opportunity to test the virulence of or- ganisms on animals, the motility is the best guide to virulence, and the rule should be: Among the available cultures select that having the most rapid motility. 4, Certain cultures contain small clumps of bacilli before any serum has been added to them. This is a very important point and has doubtless misled many. In consequence of this possibility every culture must be examined each time that a test is made. 5. Itis hardly necessary to say that the cultures used must have THE CLUMP REACTION. 463 been submitted to all the regular tests for the recognition of the typhoid bacillus, and that the greatest care must be used to avoid their contamination. The Use of Suspensions or Emulsions of the Bacilli instead of Cultures. A few observers—particularly Durham and Griber—have pre- ferred to use a mixture of small bits of solid agar culture and bouil- lon instead of bouillon cultures. The majority of writers prefer cultures. The Use of Attenuated Cultures. Johnson finds that with his methods of technique (dried blood and no definite dilution) pseudo-reactions were not uncommon with the blood of healthy people. He avoids this by using attenuated cultures—i.e., old stock agar cultures kept at room temperature and not transplanted more than once a month, from which he planted his bouillon cultures. This gives a bacillus of reduced virulence and slow, gliding motion, which is clumped far less readily than the virulent varieties. Bouillon cultures of this kind from twelve to twenty-four hours old he found to react in fifteen minutes with all typhoid sera and not with other sera even after forty-eight hours’ waiting. 3. DILUTION AND THE TIME LimIT. LI. Dilution. Ihave mentioned without explanation in various parts of this chapter that the blood serum or other fluids used must be diluted with at least ten times their volume of bouillon culture before any observation is made as to their action on the bacilli of typhoid fever. The reasons for this dilution and for the proportions 1:10 are the following: It has been found, as mentioned above, that the mere formation of clumps in bouillon cultures of Eberth’s bacilli is not a power ex- clusively possessed by typhoid serum. The serum of persons suffer- ing from other diseases and even of healthy persons will form clumps exactly like those formed by typhoid bacilli, provided it is not diluted. The only known peculiarity of the typhoid serum is that its clumping power is greater than that of other diseases, and 464 SPECIAL PATHOLOGY OF THE BLOOD. persists in spite of dilution, while the sera of diseases other than typhoid lose their power to clump typhoid bacilli when diluted ten times or more. IT, Time Limit. But even this statement must be further limited. The sera of various other diseases, and of healthy persons, will sometimes elump typhoid bacilli even in a 1:10 dilution, provided we give them time enough. We must therefore limit the period within which a serum must “come up to the scratch ” and do its work, if it is to be considered a typhoid serum. Following Griiber and Durham, a time limit of one-half hour has been adopted by Griinbaum, Block, Haedke, Park, and others. All that these more or less arbitrary figures stand for is this: that hitherto no one has reported any considerable number of cases in which the serum of any disease or of healthy persons has clumped typhoid bacilli within one-half hour, when diluted 1:10 and used with unimpeachable technique. The Microscopical Examination. An artificial light is preferable. The use of hanging-drop prep- arations is unnecessary, as a simple slide with cover-glass is satisfac- tory. A hanging-drop cell may be extemporized by cementing with marine glue a small brass curtain ring to a slide, and inverting the cover-glass within it, as advised by Stokes. LT have collected over 3,000 cases of supposed typhoid fever in which the clump reaction was tested as above described either with the fluid or dried blood. Of these, 95 per cent showed a serum reaction at some time in their course; 2,500 odd controls showed about 2 per cent of positive results in cases other than typhoid. Altogether then about 5,500 cases have been tested. If we leave out the reports of those whose experience covers less than 100 cases, we have left 4,339 cases observed by 18 physicians in which the percentage of error is 2 per cent only. How early does the reaction appear ? Few of the many observers who have written on this point have discussed how the beginning of the disease is settled and what they mean, ¢.g., by the “fifth day of the disease.” It might be dated from the first day of malaise and indisposition, from the nose-bleed or the beginning of headache, or from the time of going to bed. THE CLUMP REACTION. 465 Allowing for such serious uncertainties as this, we find that while the majority of observers record the sixth to eighth day as the earliest on which the reaction appears, there are quite a number of cases mentioned in which it was seen on the fourth or fifth day; a few record reactions present on the third day, and two or three on the second day. How late in the disease does the reaction last? The majority of observations agree that in mild cases the reaction may die out even before the end of the fever. On the other hand, the reaction usually lasts several months, and Widal found it still present after one year in 3 out of 22 cases in which he tried it. These 3 subjects had had very severe cases of typhoid three, seven, and nine years previously. It has been reported present twenty and even thirty years after the fever. The reaction almost always persists in relapses, even to a second or third relapse, and occasionally it is present only in relapse and not in the original attack ut all. Biggs and Park record a case in which the diagnosis was proved during the original attack by punc- ture of the spleen, which showed a pure culture of Eberth’s bacilli, yet no serum reaction was present until the second day of the re- lapse. I have observed several similar cases, and quite frequently not found the reaction until convalescence. The failure to follow up such cases as these accounts for many negative reports. The Intensity of the Reaction. Widal and Sicard record clumping with a dilution of 1:12,000 and 1:1,800 and consider that in the active stages of the disease a dilution of 1:60 or 1:80 does not usually present the reaction, while in convalescence the power of the serum falls off gradually and is not always present even at 1:10. Biggs and Park find one-half their typhoid cases furnish serum with the power to clump in 1:40 dilution by the end of the first week, and have occasionally noted the reaction even with a dilution of 1: 200. Control Cases. Out of over three thousand cases of various diseases not typhoid, not over a dozen have been proved to clump typhoid bacilli with proper technique. It is quite possible that further improvements in technique may enable us to prevent even this very small error. 30 466 SPECIAL PATHOLOGY OF THE BLOOD. Summary of Clinical Evidence on the Sero-Diagnosis of Typhoid Fever. The blood of over ninety-five per cent of all cases of typhoid shows a clumping power in soine part of their course, but in at least half the cases this does not appear until the second week of the disease, while in a small number of cases it first appears in relapse or convalescence. The clumping power may disappear before the defervescence and may be present only eight days in all; as a rule it persists from the sixth or eighth day until convalescence is established. In diseases other than typhoid a clump reaction is very rarely to be obtained, provided a dilution of at least 1:10 is used with a time limit of one-half hour. There is no one disease in which clumping is especially apt to occur. Clinically the reaction is of considerable value, especially when the diagnosis is in doubt after the first week of the disease. Sero-Diacnosis oF DisEASES OTHER THAN TYPHOID. 1. Cholera. Griiber and Durham first showed that human cholera serum would clump cholera vibrios, following the researches of Pfeiffer in vivo by demonstrating a similar reaction in vitro. Achard and Bensaude have applied this to the actual diagnosis of cholera in man with considerable success. In fourteen cases, thirteen clumped readily; two of these were on the first day of the disease. Thirty control cases were negative. The presence of the pellicle renders it unsafe to use bouillon cultures except such as have no pellicle, for bits of it are much like true clumps. Suspen- sions of twenty-hour gelatin cultures are more convenient. The dilution and time limit are the same as in typhoid. Some cases will react even in 1:120 dilution. The reaction can be performed with dried blood and persists into convalescence (seven months or more). 2. Malta Fever. Wright and Smith tested the serum of 15 cases of Malta fever with the micrococcus melitensis of Bruce, and found a strong clump reaction to occur (1:50 in most cases). On the typhoid bacillus the serum of these cases had no action. Sixteen cases of typhoid THE CLUMP REACTION. 467 showed no reaction with Bruce’s organism. The evidence in favor of this organism as the cause of Malta fever is strengthened by these facts. Wright’s observations have been confirmed by Neus- ser and others in this country. ‘Curry in a very recent number of the Boston Medical and Sur- gical Journal reports eighteen cases with clumping. 3. The Bubonic Plague. Zabolotny’ studied forty cases at Bombay in April, 1897, and found the reaction absent in the first week, present in 1:10 dilution in the second week, and in 1:50 dilution in the third or fourth week. He noted that the action of the infected serum seemed to deprive the bacilli of their capsules. In an editorial in the Arch. Russes de Pathologie, May 31st, 1897, it is stated that the reaction increases in intensity until the fourth week of the disease and then declines; also that it is most marked in the severest cases. Fein- del (loc. cit.) states that in the acute pneumonic cases the reaction is absent. 1Deut. med. Woch., 1897, p. 392. APPENDIX A. Nevusser’s PERINUCLEAR BAsoPpuitic GRANULES. Usine the following modification of Ehrlich’s tricolor mixture, Neusser’ believes that he can bring out certain characteristics in the leucocytes of value in diagnosis and prognosis. Acid fuchsin................ 50 c.c. Saturated aqueous solution of { Orange G............00 eens 70 “ Methyl green............... 80 * Distilled waters cvsieusy sesiss titers ees cocu Auandei neers aaa 150 “ Absolute AlCOHOL: 3.5 csseee vaca aoe ewae Noleaie wae aes setae 80 “ GUY COME witst a-toarsbins cate aw wouaiaaeeeicd a athe bew ai eke a eetee 20 “ Cover slips stained with this mixture show in certain diseases (e.g-, gout, leukemia) a grouping of dark blue-stained granules around the nuclei of the mononuclear leucocytes and over and around the nuclei of polymorphonuclear leucocytes. These granules ap- pear to take up only the basic part of the tricolor mixture. For Neusser’s conclusions regarding the meaning of these gran- ules, the reader is referred to pages 274 and 351. The researches of Futcher have in my opinion utterly disproved Neusser’s claims. The granules are of no known clinical significance and certainly have no direct relation to gout or any other alloxuric diathesis. I have a triple stain (not made up for the purpose) which brings out Neusser’s granules in every blood, normal or abnormal. 1 Wien. klin. Woch., 1894, No. 39. SPECIAL PATHOLOGY OF THE BLOOD. 470 OF-Ge “*** 1 900‘0¢8‘T qe Gece) curses | Boers et 18 | 000‘0T | 000‘0g9‘T UHL 08 | 00001 | 000‘09F'T Wp “AON + = : : G8 | 000‘°6T | 000‘008‘T | 68at ‘WIGS “390 | 9 pee Ses as ‘ ; ““** | 900‘9 | 000‘8F8 | 888T “ISTE “APPL | ¢ 000 ‘8SF‘% UIST 000 Fee '3 wr “PO 0000838 Se 000 ‘086 ‘T TIGL urd | 000‘89L'T wg “deg yg “Sny | F + - ee “u2ag ce oe ie ee Ca F images ORR RRS | ee he Kw 988T WHT Ane TRULION] 000‘016‘T WLS [RWION] 000‘88S‘T | S88T ‘TIE “Sny 98st ‘wi Aine] ¢ : 000‘e¢ pg “AON OOL‘T | 000‘F9¢ WLS 000‘F9S TST “[BULION] 000‘089° pg g ; 000‘893°8 PS "300 000% | OSL ‘TTs‘s ad ., | 000°0F3'T WHT 000°8 | 000‘088‘T | 888T “TI0T 000‘e¢2¢ TL “ydag OST ‘TI'S | eset ‘We ANE | T B_|8 |3 /8 ao! 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APPENDIX C. 483 TABLE SHOWING GRADUAL INCREASE IN §1ZE OF RED CELLS DURING CoNVALESCENCE OF CHLOROSIS. Case I. 2 RED CELLS—DIAMETER. er Col Date. | Red cells. cont. Color Geant leas ees auereuen 0 fe UK ed fh, 10 Me age. p. ct.| p.ct. | p.ct. | p.ct.| p. ct. May 16th | 4,950,000}....) .... |J....] .... |... Jowee | eee. : 17th | 5,247,000] 41 | 0.46 || 5.0 | 64.0 | 81.0) 1.0] 7.46 { Ovarian June 8th | 5,717,000] 44 | 0.46 || 1.5 | 59.5 | 37.0 |. 2.0 | 5.55 || | extract. 15th | 5,740,000} 57 | 0.59 |} 1.0 | 52.5 | 41.5 | 5.0 | 7.71 23d | 6,332,000] 61 | 0.57 || 4.0 | 48.5 | 42.5 | 5.0] 7.68 30th | 6,030,000] 61 | 0.60 || 2.5 | 41.0 | 49.0 | 7.5 | 7.85 |] | Blaud’s July 7th | 6,375,000] 65 | 0.60 || 3.5 | 88.5 | 52.5 | 5.5] 7.84 pill. 17th | 5,730,000] 70 | 0.72 || 8.5] 41.0] 58.0] 2.5 | 7.76 26th | 5,687,000] 72 | 0.75 || 1.5 | 44.0 | 52.5 |) 2.0] 7.77 Aug. 10th | 5,792,000] 72 | 0.73 ||....] .... | o... [eee | eee Cask II. May 29th | 3,900,000| 80 | 0.45 || 0.5 | 56.5] 43.0]....| 7.44 June 18th | 4,398,000] 43 | 0.56 |) 2.5 | 51.5 | 44.5] 1.5] 7.64 || | Ovarian 25th | 4,740,000] 49 | 0.61 || 1.0 | 49.0 | 47.5 | 2.0 | 7.67 || ( extract. July 2d | 4,730,000| 47 | 0.59 |) 2.0 | 48.5 | 48.5) 1.0 | 7.68 9th | 5,884,000] 57 | 0.58 || .. | 38.0] 53.0] 9.0] 7.99 15th | 5,667,000] 65 | 0.67 || 2.0 | 38.5 | 52.0] 7.0 | 7.91 || | Blaud’s Aug. 4th | 6,437,000| 71 | 0.65 |} 1.5 | 39.0 | 54.0 |10.5 | 7.94 pill. 17th | 6,040,000] 71 | 0.69 || 1.5 | 31.0] 59.0] 8.5 | 8.04 Case ITI. Oct. 17th | 3,701,000] 27 | 0.43 |] 2.0 | 68.5 | 29.5 ]....] 7.87 24th | 4,855,000| 89 | 0.47 || 1.0 | 61.5 | 340] 3.5 | 7.55 |! | pana : 31st | 5,230,000] 58 | 0.60 || 2.0} 47.5 | 45.5 | 5.0] 7.74 a Nov. 12th | 6,021,000] 72 | 0.71 || 1.0] 39.0 | 59.5 | 5.5 | 7.97 pi. 20th | 6,205,000] 80 | 0.76 || 1.0} 18.0] 72.0] 9.0 | 8.24 Case IV. Dec. 12th | 4,255,000] 40 | 0.56 |) 1.5 | 63.0) 35.5]....| 7.48 l1) pang 28th | 6,105,000] 65 | 0.63 || .. | 52.0] 44.5] 3.5 | 7.72 il 8 Jan. 13th | 6,066,000] 71 | 0.69 || 2.0 | 36.5 | 60.0 | 1.5 | 7.80 pi 484 SPECIAL PATHOLOGY OF THE BLOOD. APPENDIX D. THOMAS R. BROWN’S FIRST CASE OF TRICHINOSIS. SHowine Tota NuMBER AND PERCENTAGE OF Various Kinps oF LEv- COCYTES. PERCENTAGE OF VARIOUS FORMS |} NUMBER OF THE VARIOUS FORMS OF LEUCOCYTES. PER C.MM. pase, | Ce P.M. Ss. L. M. Neut. |Monos.|anaT.| 28. 9,850] 510} 850] 6,300 8,250] 825] 1,120) 6,120 9,275 | 525) 1,200] 6,300 15.000} 500} 1,500 | 7,750 15,300 | 440) 900} 5,060 12,000 | 480] 1,280] 2,400 15,800] 630] 500] 3,700 13,600} 770} 510) 2,625 13,860} 3880) 710] 3,000 10,800} 580} 560) 2,100 10,800 | 1,000} 420; 1,720 10,400] 680] 270) 1,700 11,700] 1,770} 310] 2,160 18,800 | 1,970] 800) 1,775 14,200 | 2,600] 460! 2,600 12,100 | 1,570} 3840] 1,760 12,400 | 1,210] 3820] 2,040 11,200 | 1,540] 240} 1,130 12,400 | 1,700} 270) 2,200 14,800 | 2,200] 360] 2,200 14,400 | 1,600} 290] 1,560 P.M. Ss. Neut. | Monos. | a Mar. 5th | 17,000] 55.0 6th | 16,500 | 50.0 7th | 17,500 | 53.0 8th | 25,300} 60.9 9th | 22,3800] 70.8 10th | 16,500] 74.7 11th | 21,167 | 75.1 12th | 17,500 | 77.8 18th | 18,833 | 776 14th | 13,800 | 74.6 15th | 18,750] 74.0 16th | 18,250 | 78.7 17th | 16,000 | 73.2 18th | 17,750) 77.4 19th | 20,400 | 71.1 20th | 15,700 | 76.5 2ist | 16,800 | 72.9 22d | 14,000 | 79.2 23d | 16,800) 73.6 24th | 19,600 | 74.6 25th | 17,600] 80.4 Bo e. 5 I 9° mn ~ o Re Eee eee VOANMNIHDOOAIN DA WHY ER WSHWERSNDHAER SSS Bee eee BWADSWAGSOWBONRKYKHSOSOHHSOOSVOBRUNNWHEWHOUNKASHSHOURIREOS PS AS AN DAD OWS WO rs OT TB OB COW EL CO OT BWDAWHDHOWWANSWHWHWAOWAIHWNIOW ROVE HOWWOWEURDUSCOS He BE 20 20 OO Pt £0 PR CO G9 HR RD GO HR 00 00 69 GO 09 COA WW PAP EH Et WE EL COR Oo OO DO ROTI OT DROADEMNODWSCURSCSCHSOBNYSOKRHKWOABDRIBDYWWNOHWSNSOHKROMOEOS 26th | 24,000] 69.2 | 1 1 16,800 | 3,120} 480) 3,700 27th | 20,800 | 69.9 | 1 1 14,000 | 2,240] 440] 3,200 28th | 24,100] 68.3 | 1 1 16,800 | 2,400] 580} 4,560 29th | 20,700 | 69.4 2 14,000} 1,180] 300] 4,600 30th | 22,300 | 60.7 2 13,400 | 2,200} 670] 5,720° Bist | 22,200] 57.4 | 1 2 12,600 | 2,500} 680] 6,160 Apr. ist | 24,300 | 60.7 ts 2 14,400 | 1,920} 840] 6,720 2d | 23,800} 59.3 | 11. 2 14,100 | 2,760 | 710] 5,950 3d | 25,200) 53.3 | 18. 3 13,300 | 3,300] 700} 7,500 4th | 23,400 | 49.9 | 13. 3 11,700 | 3,200] 710} 7,590 5th | 24,800 | 48.8 | 13. 33 10,100 | 3,150] 960} 7,160 6th | 24,700 | 51.2 | 14. 31. 12,700 | 8,500} 650) 7,900 7th | 25,100 | 48.4 | 14. 33. 12,100 | 3,600 | 625] 8,600 8th | 29.600 | 45.2 | 11 38. 13,500 | 8,450 | 1,180 | 11,600 9th | 28,900 | 45.0 | 18. 38. 13,000 | 3,850 | 930) 11,000 10th | 24,500 | 45.8 | 12. 38. 11,300} 3,100] 900] 9,300 11th | 29,800 | 42.2} 14. 39. 12,600 | 4,150 | 1,180 ; 11,900 12th | 28,000 | 44.0 | 14. 38. 12,3800 | 4,150 | 700 | 10,800 13th | 24.200 | 42.0 | 11. 44 10,000 | 2,880] 3840 | 10,700 14th | 33,300 | 38.6 | 13 44. 12,800 | 4,400 | 1,300 | 14,700 15th | 28,100] 34.8 | 19 44, 8,600 | 5.550 | 450 | 12,300 16th | 25,400 | 30.4] 16. 49. 7,600 | 4,200} ‘750 | 12,400 17th | 27,000 | 31.8 | 13. 51. 8,600 | 3,500 | 920 | 18,700 18th | 35,700] 27.2 | 14. 54. 9,700 | 5,140 | 360 | 19,500 APPENDIX. 485 PERCENTAGE OF VARIOUS FoRMS || NUMBER OF THE VARIOUS FORMS ee oF LEUCOCYTES. PER C.MM. ors wes: ow | sg L.M P.M s L.M Neut. | Monos.| ana ‘t. | £9: Neut. |Monos.| and T.| 298- Apr. 19th | 29,000 | 26.6 | 12.0 3.6 | 58.2 7,700 | 3,480 | 1,040 | 16,900 20th | 19,200 | 22.2 | 12.4 4.2 | 61.0 4,200 | 2,350 800 | 11,600 21st | 23,000} 16.6 | 16.0 3.8 | 63.6 3,800 | 8,680 870 | 14,600 22d | 26,600] 10.4 | 18.8 7.4 | 63.4 2,700 | 4,900 | 1,950 | 16,500 23d | 17,700 6.6 | 19.6 5.2 | 68.2 1,170 | 38,400 880 | 11,070 24th | 18,800 7.2 | 28.4 4.4 | 64.8 1,370 | 4,400 840 | 12,200 25th | 15,600 8.8 | 19.2 7.2 | 64.8 1,370 | 2,990 | 1,020 | 10,400 26th | 17,000} 12.4] 14.2 6.0 | 67.4 2,100 | 2,410 | 1,020 | 11,450 27th | 12,000 | 20.0 8.6 74 | 64.0 2,400 | 1,030 890] 7,700 W8th | 11,100] 18.2 | 17.6 7.2 | 57.0 2,020 | 1,950 800 | 6,330 29th | 12,800] 19.4] 19.4 6.8 | 54.4 2,470 | 2,480 870; 6,990 30th | 13,200] 20.8 | 17.2 8.2 | 53.8 2,700 | 2,270 | 1,080] 7,020 May 1st | 11,000 | 21.8 | 16.0 | 12.0 | 50.2 2,400 | 1,760 | 1,820] 5,520 2d 8,900! 27.4) 17.8 8.4 | 46.4 2,440 | 1,580 740 | 5,160 Bd | 10,700} 36.8} 150 6.8 | 41.4 8,940 | 1,600 710] 4,430 4th | 10,700 | 34.8 | 20.8 6.4 | 38.0 3,720 | 2,120 680 | 4,070 5th | 11,000 | 45.6 | 19.0 6.6 | 28.6 5,020 | 2,090 710 | 3,150 6th | 10,300 | 41.0 | 20.2 | 48 | 33.6 4,220 | 2,080 490} 3,460 7th | 12,800 | 50.8 | 20.2 6.0 | 23.0 6,250 | 2,480 740] 2,830 8th | 11,500 | 54.0 | 18.0 4.0 | 24.0 6,210 | 2.070 460 | 2,760 9th | 11,500 | 59.8 | 17.6 6.2 | 16.4 6,850 | 2,020 710} 1,890 10th } 15,700 | 51.0 | 12.8 5.6 | 20.4 7,100 | 2,010 880 | 3,200 11th | 13,500 | 62.4 | 14.2 4.8 | 18.8 6,420 | 1,920 650 | 3,540 12th | 11,000 | 64.0] 14.4 4.8 | 16.8 7,040 | 1,580 580} 1,850 %, BIBLIOGRAPHY. Ir has seemed to me best to give a list only of the books and articles which I have found most useful, since the general bibliog- raphy of the subject is now large enough to form a volume by it- self. Most of the larger works here described contain extensive bibliographies— especially that by Ewing. Text-Books. 1. Ewing: “Clinical Pathology of the Blood,” Philadelphia, 1901, 8vo, 432 pages (Lea Bros.). This is the newest book on the blood and the fullest discussion of the theoretical points connected with diseases of the blood. The bibliography and résumé of the work of other observers contained in each section are admirable. The original observations of the writer are contained chiefly in the chapters on malaria and diphtheria. The tone of the book is ad- mirably sane and judicial throughout. The illustrations are poor. 2. Ehrlich, Lazarus, Pinkus, and v. Noorden in vol. viii. of Nothnagel’s “Specielle Pathologie und Therapie,” issued between 1898 and 1901 (Wien, Holder & Co.) have written a series of articles on anemia, leukemia, and chlorosis, which together amount to many pages 8vo. The clinical aspects and therapeutics of the diseases are included. The hematology of the book is on the whole inferior to Ewing’s, although parts of it, especially v. Noorden’s study of chlorosis, are masterly. The articles on anemia are interesting as they contain Ehrlich’s latest utterances. The work is out of date in some re- spects owing to its characteristically Teutonic ignorance of important work done in England and America, but it is undoubtedly the standard German work on the subject. 3. Hayem: “Du Sang,” Paris, 1889, 8vo, 1035 pages (French). This val- uable book is the largest that I know of on the subject, and contains a mine of information on the morphology of the blood in health and disease, mostly from the author’s own experience, literature being but little referred to. It contains a comparative anatomy of the blood and a long account of blood de- velopment. Unfortunately, it is dominated-throughout by a theory of blood formation which has never gained acceptance by any other authority. It is very full on the subject of fibrin formation and of chlorosis. The illustrations are excellent. In a later work, “Lecons sur les Maladies du Sang,” Paris, 1900, 8vo, 700 pages (Masson et Cie.), Hayem has brought his previous book in a measure up to date, but the “Lecgons” are very diffuse and wordy and 488 BIBLIOGRAPHY. contain but a small fraction of the original work for which Hayem’s first book was so notable. 4. v. Limbeck: “Grundriss ein. klin. Pathologie des Blutes,” Jena, 1896, 8vo, 383 pages (Fischer). The second edition of this book, which appeared in February, 1896, is more than twice the size of the first edition (1892)—a fact illustrating the rapidity of the subject’s growth. It is on the whole the best general text-book known to me, being equally full on all parts of the subject, including, for example, technique (which Grawitz omits) and of the chemistry of the blood, which is at present the author’s special interest and on which Hayem is meagre. The illustrations are poor and the type is trying to the eyes. The writer shows little personal experience with the morphology and micro-chemistry of the blood, and this is the weakest side of the book. A large part of the book is concerned with the physiology of the blood. 5. Grawitz: “Klinische Pathologie des Blutes,” Berlin, 1895, 8vo, 333 pages (Enslin). Issued in April, 1896. This book is largely devoted to the matter indicated by the title and contains no account of blood technique, and only thirty pages on the normal anatomy and physiology of the blood, while two hundred and seventy concern the blood in disease. The arrangement of the book is very clear and helpful. The author’s main interests are in the estimation of the dried residue of the blood in various diseased conditions and in the bacteriology of the blood, so that the book is specially full on these topics. The illustrations are poor. Type and paper are excellent. 6. Coles: “The Blood: How to Examine It,” etc., London, 1898 (J. and A. Churchill), 8vo. A clear and fairly complete account of the work of others upon the subject. Especially full on technique. These are the best text-books known to me on the whole subject. Taylor’s masterly monograph, entitled “Studies in Leukemia” and forming part of the volume of “Contributions from the William Pepper Laboratory of Clinical Medicine” (Philadelphia, 1900), contains within its one hundred and seventy-eight quarto pages not merely an unrivalled account of leukemia but a great deal of im- portant matter on leucocytosis, anemia, and most other hemato- logical topics. It is by far the best study of leukemia known to me in any language. Treatises on Special Portions of the Subject. 1. Reinert’s “ Die Zihlung der Blutkérperchen,” Leipzig, 1891 (Vogel), 246 pages, is an admirable account of the avoidable and unavoidable errors in blood examination, and the best methods of reducing error toa minimum. A number of careful examinations of the blood in health and in various diseases are also given; and an outline of the scope of blood diagnosis closes the book. 2. Tiirk’s monograph ‘on the “Condition of the Blood in Acute Infectious Disease” is an admirable résumé of German and French literature on the sub- ject, together with a detailed study of fifty-two cases. Published at Wien and Leipzig, 1898 (Braumiiller), 347 pages, 8vo. BIBLIOGRAPHY. 489 8. Rieder’s “Beitrige zur Kenntniss der Leukocytosis,” Leipzig, 1892 (Vogel), 220 pages, is an admirable work in all respects, although now consid- erably out of date. It shows, as very few of the foregoing treatises do, a practical acquaintance, on the author’s part, with the details of blood mor- phology and microchemistry. A very large number of blood counts in many diseases are recorded. 4, Lowitt’s “Studien zur Physiol. und Pathol. des Blutes u. der Lymphe” (Jena, 1892 [Fisher], 8vo, 138 pages) is mostly concerned with experiments on animals and intended to throw light on the theory of leucocytosis. The con- clusions of the book have not been generally adopted, though its facts have been mostly verified. 5. Thayer and Hewetson’s book, on the “ Malarial Fevers of Baltimore,” leaves nothing more to be desired in that direction. It is two hundred and fifteen pages long, published by the Johns Hopkins press of Baltimore in 1895. It contains a summary of the literature of the subject, an analysis of six hun- dred and sixteen new cases, and some admirable colored plates. It is a model of its kind in every respect, and an ideal for others to aim for. Essentially the same material is reorganized in Thayer’s “ Lectures on the Malarial Fevers,” New York, 1899, Appleton. 6. Ehrlich’s “ Farbenanalytische Untersuchungen” (Berlin, 1891 [Hirsch- wald], 137 pages) contains nine short essays by Ehrlich and three by his pu- pils. Considering the reputation of the writer they are at the present day rather disappointing reading, and contain little that is not better expressed elsewhere. 7. Weiss’s “Hematologische Untersuchungen” (Wien, 1896 [Prochaska] 112 pages, 8vo) contains many valuable studies on various points. Magazine Articles of Special Value. 1. On Concentration and Dilution of the Blood—Oliver: Lancet, June 27, 1896. 5 2. On Leucocytosis—Goldschneider and Jacob: Zeit. fiir klin. Med., 1894, vol. 25. Krebs: Inaug. Dissert., Berlin, 1893. Sadler: Fortschr. d. Med., Supplement-Heft, 1892. Also Klein, in Volkmann’s Sammlung klinischer Vortrige, December, 1893, and of course Rieder and Tiirk above referred to. 3. On Anemia—Dunin: Volkmann’s Sammlung klin. Vortriige, 1896, No. 185. Romberg: Berlin. klin. Woch., June 28, 1897. 4, Parasitic Anemia—Schaumann: Zur Kenntniss der sog. Bothriocepha- lus Aniimie, Berlin, 1892, 214 pages; and Askanazy: Zeitschr. f. klin. Med., 1895, p. 492. Brown: Journal of Experimental Medicine, May, 1898 (Trichi- nosis). 5. Leukemia—Fraenkel: Deutsche med. Wochenschrift, 1895, p. 639. Fraenkel: 15th Congress fiir inn. Medicin, Wiesbaden, 1897. Benda: Ididem. Dock: Moscow Internat. Congress, 1897. 6. Pernicious Anzmia—Discussion by Birch-Hirschfeld, Ehrlich, Troje, and others, at the XI. Congress f. inner. Med. (Leipzig, 1892). 7. Pneumonia—Billings: Bulletin of the Johns Hopkins Hospital, Novem- ber, 1894. Diphthberia—Billings: New York Medical Record, April 25, 1896. 490 BIBLIOGRAPHY. Typhoid—Thayer: Johns Hopkins Hospital Reports, vol. iv., No. 1. Engel. 15th Congress fiir inn. Med., Wiesbaden, 1897. Exanthemata—Felsenthal: Arch. f. Kinderheilk., 1892, p. 78. Zappert: Zeitschr. f. klin. Med., 1893, No. 28. Smallpox—Pick: Arch. f. Dermatol. und Syph., 1898, p. 68. Sepsis —Roscher: Inaug. Dissert., Berlin, 1894. Cholera—Biernacki: Deutsche med. Wochenschr., 1895, No. 48. Diabetes—Bremer: Moscow Internat. Congress, 1897. 8. Syphilis—(a) Reiss: Arch. f. Dermat. und Syph., 1895, Hft. 1 and 2. (0) Justus: Virchow’s Arch., 1895. 9. Tuberculosis—(a) Dane: Boston Medical and Surgical Journal, May 28, 1896. (5) Stein und Erbmann: Deutsche med. Wochenschrift, 1896, No. 56, p. 823. (c) Grawitz: Deutsche med. Wochenschr., 1893, No. 51. 10. Malignant Disease—Taylor (International Medical Magazine, July, 1897). (a) Sadler: Loe. cit. () Reinbach: Langenbeck’s Archiv, 1893, No. 46. (c) Strauer: Dissert., Greifswald, 1893. 11. Bacteriology—Sittmann: Deutsches Arch. f. klin. Med., vol. 53. 12. Diseases of the Stomach (especially Cancer)—Schneyer: Zeitschrift f. klin. Med., 1895, p. 475. Osterspey: Inaug. Diss., Berlin, 1892. 13. Eosinophiles—Zappert: Zeitschr. f. klin. Med., 1893, vol. 28. 14. Hemoconien—Miller: Wien. med. Presse, 1896, No. 36. INDEX. ABSCESS, 205, 239 diagnostic value of blood in, 252 felon, 251 gum boil, 251 of liver, 315 of lung, 251 of neck, 251 of ovary, 251 of parotid, 251 of vulva, 251 perinephritic, 251 psoas, 251 subpectoral, 251 subphrenic, 251 vaginal, 251 Actinomycosis, 256 Acute yellow atrophy of liver, 311 Addison’s disease, 354 Adenitis, 176 Alcoholism, 366 Alkalinity of blood, 49 Altitude, effects on blood, 78 Ameceboid movements, 58 Anemia, 80 aplastic, 152 infantum pseudoleukemica, 450 of infancy, 447 pernicious, 131 primary, 81 secondary or symptomatic, 83 splenic, 185 tropical, 81 with dilated stomach, 300 with ulcer of stomach, 293 Aneurism, 326 Antitoxin (diphtheria), 210 Appendicitis, 240 diagnosis of, 246 fibrin in, 243 Bacrerio.oey of the blood, 47 in pneumonia, 189 Basedow’s disease, 353 Beri-beri, 257 Bleeders, 8 Blood destruction, 358 Bronchitis, 205, 337 acute, 338 Bronchitis, chronic, 339 Brownian movement, 11, 85 Bubonic plague, 255, 467 Burns, influence on blood, 3861 CaIsson disease, 346 Cancer, 370 eosinophiles in, 392 generalized, 390 leucocytes in, 377 myelocytes in, 392 nucleated red cells in, 376 of abdominal organs, 387 of breast, 379, 390 of gullet, 384 of intestine, 386 of kidney, 388, 390 of lip, 390 of liver, 385 of mediastinum, 390 of neck, 390 of omentum, 387 of ovary, 390 of pancreas, 390 of prostate, 390 of skull, 390 of stomach, 380 of stomach, digestion leucocyto- sis in, 382 of uterus, 389 of vertebrx, 390 position of tumor and its influ- ence, 377 qualitative changes in blood, 875 qualitative changes in leuco- cytes, 391 regeneration of blood in, 874 Cathartics, influence on blood, 801 Charcot-Leyden crystals, 170 Chlorosis, 153 blood plates in, 158 deformities in, 156 diagnosis of, 159 eosinophiles in, 158 lymphocytes in, 158 myelocytes in, 158 neutrophiles in, 158 red cells in, 154 492 Chlorosis, specific gravity, 157 volume of blood in, 153 white cells in, 157 Cholemia, 312 Cholangitis, 314 Cholecystitis, 205, 314 Cholera, 226 acidity of blood in, 226 serum reaction in, 466 Chorea, 346 Cirrhosis of liver, 307 Coagulation in jaundice, 48 in pernicious anemia, 49 in purpura, 48 of blood, 65, 69 Concentration of blood, 75 Conjunctivitis, 205 Constitutional diseases, 349 Convulsions, effect of, 346 Corpuscles, biconcavity, 52 crenation, 52 number of, 56-59 red, effects of fatigue on, 58 resistance, 49, 51 white, 53 Counting corpuscles, 12-27 corpuscles (differential), 46 Cretinism, 3538 Cyanosis, 190 Cystitis, 205 DEGENERATION of corpuscles, 52, 191 Diabetes, 349 Diarrhea, 9 Digestion leucocytosis in cancer, 382 Digestive organs, diseases of, 292 Diphtheria, 210 Distribution of blood, 72 Dunham’s hemocytometer, 23 Duodenal ulcer, 297 Dysentery, 209 Dyspepsia, 298 Ecutnococcvs cyst, 311 Electric shock, 869 Electricity, effect on blood, 50 Emphysema, 340 Empyema, 262 Endocarditis, 316 Endoglobular changes, 84 Eosinophiles, 65, 184, 193, 206 Eosinophilia after tuberculin, 274 compensatory, 117 diagnostic value of, 118 in acute and chronic skin dis- eases, 115 in ankylostomiasis, 116, 428, 432 in asthma, 340 in cancer, 116, 392 in fibrinous pneumonia, 115 INDEX. Eosinophilia in hematoma, 117 in helminthiasis, 116 in purpura, 117 in scarlatina, 216 in trichinosis, 116, 485 medicinal, 117 physiological, 115 post-febrile, 116 Epidemic dropsy, 256 Erysipelas, 227 Erythema nodosum, 209 Facau impaction, 247 Fever, influence of, 188, 198 Fibrin, 54, 121, 198 Filariasis, 417 Furunculosis, 204 GALL-STONE Colic, 247 Gall stones, 312 Gastric ulcer, 293-297 Gastritis, acute and chronic, 298, 299 corrosive, 301 digestion leucocytosis in, 300 in infancy, 449 with hyperacidity, 300 General paralysis, 346 Glanders, 255 Gonorrhea, 253 Gout, 351 Gowers’ solution, 13 Graves’ disease, 358 Grippe, 229 Gumma of liver, 315 HaMarocnrirt, 31 Hemocytolysis, 360 Hemoglobin, 32, 120 Hemoglobinemia, 360 Hemoglobinometers, 32-37 Hemophilia, 359 Hayem’s solution, 27 Heart, congenital disease of, 323 diseases of, 316-823 Heat exhaustion, 368 Hemorrhage, 1238, 202 blood degeneration after, 123 chronic, 127 Hodgkin’s disease, 179, 453 Hydremia, 93 Hydronephrosis, 176 Hy pochondriasis, 347 Hysteria, 347 InFANcy, anemias of, 447 blood in, 445-456 chlorosis in, 448 hereditary syphilis in, 449 leucocytosis in, 445 leukeemia in, 456 INDEX. Infancy, lymphocytosis in, 445 polycythemia in, 445 rickets in, 449 Tnfluenza, 209 Intestinal parasites, 426, 440 Intestine, disease of, 301 obstruction of, 304 Iodophilia, 239 Isotonic coefficient, 50 JAUNDICE, catarrhal, 304 coagulation in, 805 Justus reaction in syphilis, 288 Kipneys, diseases of, 247, 327-337 pyonephrosis, 337 uremia, 3384 s Leprosy, 291 Leucocytes, 58 degenerated, 70 eosinophilic (see Eosinophiles), 64 in abscess, 239 in smallpox, 219 iodine reaction in, 239 mononuclear neutrophilic, 65, 68, 70 normal percentages of, 67 origin of, 67 polymorphonuclear, 65 “stimulation forms,” 71 transitional neutrophiles, 71 Leucocytosis, absence of, 111 after exercise, massage, baths, 100 cell changes in, 96, 110 definition, 94 diagnostic value of, 98 digestive, 97 experimental, 109 inflammatory, 104 in malignant disease, 108 in new-born infants, 99 in pneumonia, 191 in pregnancy, 100 in shock, 106 pathological, 104 physiological, 95 post-hemorrhagic, 104 post-partum, 100 terminal, 108 therapeutic, 109, 178, 192 toxic, 107 Leucopenia, 112, 185 Leukemia, 160-185 remissions in, 170 Lipemia, 122 Lymphemia, 170 Lymphatic leukemia, 170 Lymphocytes, 62 and 493. Lymphocytosis, 113 in hereditary syphilis, 113 in infancy, 113 in pertussis, 113 in splenic tumors, 114 in thyroidism, 114 Macrocytes, 88, 155 Malaria, 176, 238, 404-416 parasites of, 404 pigmented parasites, 405 segmenting parasites, 405 typhoid, 208 Malta fever, 255, 466 Mast cells, 66, 169 Megaloblasts, 88, 162, 190 Melanemia, 122 Meningitis, 209, 266-268, 282 tuberculous, 282 Mental diseases, 348 Microblasts, 90 Microcytes, 83 Miilier’s blood dust, 60 Myelocytes, 68, 118, 165, 194, 347, 392, 399, 450 Myeloid leukeemia, 161, 177 Myxcedema, 351 Necrostosis of red cells, 83 Nephritis, 327 Nervous system, diseases of, 343-345 Neuralgia, 246 Neurasthenia, 347 Neuritis, 343 Newton’s rings, 15 Normoblasts, 87, 162, 190 Nucleated red cells, 190, 376, 481 OBEsITY, 349 Oliver’s instruments, 23, 27, 35 Osteomalacia, 355 Osteomyelitis, 251 Otitis media, 205 ’ PancrREAs, diseases of, 315 Parasites, filarial, 417 intestinal, 426 malarial, 402 of the blood, 402, 426 Parotitis, 205 Pericarditis, 205, 265, 285 tuberculous, 285 Periostitis, 205 Peritonitis, 264 tuberculous, 280 Pernicious anemia, 131 anemia, diagnosis of, 146 anemia, gross appearance of blood, 131 anemia, hemoglobin in, 136. 494 Pernicious anemia in infancy, 452 anemia, nucleated red cells in, 39 anemia, prognosis in, 149 anemia, red cells in, 182, 137 anzemia, remissions in, 144 anemia, white cells in, 135, 142 malaria (see Malaria) Phosphorus poisoning, 311 Phthisis, 271, 278 Pipettes, use and care of, 18 Platelets, 58, 198 Plethora, 74 Pleurisy, purulent, 262 serous, 204, 259 tuberculous, 285 Plumbism, 367 Pneumonia, 176, 189, 204 bacteriology of blood, 187 broncho-, 197, 205 Poikilocy tosis, 83 Poisoning, by ammonia, 365 by antipyretics, 361, 363 by arsenic, 366 by carbolic acid, 366 by carbonic oxide, 79, 363 by ether, 865 by illuminating gas, 368 by lead, 367 by opium, 365 by phosphorus, 311, 363 by potassium chlorate, 361 by ptomains, 3865 by pyrogallic acid, 363 by snake venom, 361 by tansy, 365 effects on blood, 363 Polychromatophilia, 86 Polycythemia, 72-74 Pregnancy, 247 Purpura, 358 Pus tube, 248 REGENERATION of blood, 124 Relapsing fever, 257, 422 Rheumatism, 221-226 Rickets, 356, 449 Rouleaux formation, 51 Sarcoma, 394-399 Scarlatina, 215 Scurvy, 359 Septiceemia, 230-237 INDEX. Boras membranes, diseases of, 259+ 26 Serum diagnosis, 458 diagnosis of bubonic plague, 467 diagnosis of cholera, 466 diagnosis of Malta fever, 466 diagnosis of typhoid, 458 Skin, diseases of, 442 Slides, preparation of, 9, 41 Smallpox, 217 Snake poison, 361 Solids of the blood, 50 Specific gravity of blood, 39, 190, 198 Splenectomy, 184 Splenic anemia, 185 extract, 178 myeloid leukemia (see Leuke- mia) Staining blood films, 48, 64, 61 Sunstroke. 21 Syphilis, 286-290, 449 TETANUS, 257 Tetany, 346 Thoma-Zeiss’ instruments, 138, 15 Thrombosis, 204 Thyroid extract, effects of, 351 Toisson’s solution, 13 Tonsillitis, 228 Toxicity of blood, 190, 200 Trichinosis, 209, 484 Tuberculosis, 269-286, 449 acute miliary, 277 fibrin in, 270 glandular, 285 leucocytes in, 271 of bone, 275 of meninges, 282 of pericardium, 285- of peritoneum, 280 Typhoid fever, 197-207 fever, serum reaction in, 458 UReEruritis, 205 Uric acid in blood, 351 VACCINIA, 220 Varicella, 221 Variola, 219 YeEuuow fever, 253 ZAPPERT’S counting-chamber, 16 DEE EA a CER RINNE Prue a We vei NUNC RA a Ia MI Fiey PU DA) on EN aM 7 ae ist Ae BD Mana ee oe) Sa eee, Pe Ds ae DSPs eo i eee Ai ae DOS OLA ta) 0 p D a oD bt Ror obs) tits ah et PaO as Wma bien heat angi Pare) MTT MACON trtetetecittey fe Shey a 4 1. r ss Webi Sony tk a ASN H hae! 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