:i?V> ^^^iiiH^^H THE LIBRARY OF THE UNIVERSITY OF CALIFORNIA LOS ANGELES GIFT OF SAN FRANCISCO COUNTY MEDICAL SOCIETY RADIUM THERAPY KADIUM THHEAPY BY FRANK EDWARD SIMl^SON, A.B., M.D. PliOFESSOR OP )>EI;^rATOI,OGY, CITICACO POLICLIXIC; ADJUNCT CLINICAL PROFESSOR OF l)EKMATOLO(iV, NOKTl 1 WESTERN I'NIVERSITY MEDICAL SCHOOL; ATfENDINCf DER- MATOLOGIST TO JIEKCY HOSPITAL, ALEXIAN BROTHERS HOSPITAL, HEXKOTIN HOSPITAL, ETC. ; FORMER PRESIDENT AMERICAN RADIUM SOCIETY ; FORMER VICE CHAIRMAN, SECTION OF DERMATOLOGY^ AND SYPHILOI/K! Y, AMERICAN MEDICAL ASSOCIATION; DIRECTOR OF THE FRANK EDWARD SIHrPSON RADIUM INSTITUTE. U77// liiii OlxKllSAL KM;h'A\'lM!S ST. LOTHS C. V. MOSBY COMPANY 1922 Copyright, 1922, By C. V. Mosby Company (All rights reserved) Printed in U. S. A. Press of The C. V. Mosby Comt^auy St. Louis labrary TO M. B. L. S. MY WIFE 5*7 7 *• 64 PREFACE Tlie completed mciiiuseript of this book was given to tlic pu])lishers on July 6. 1921. The delay in publication, due to unusual industrial con- ditions, has enabled me to make some minor corrections in the clinical part of the work and to bring the bibliography up to date. A survey of the literature referred to in the bibliography, Avhich I have tried to make comprehensive rather than critical, indicates the wide- spread interest in radium therapy. XTnfortunately, lack of space has made it possible to mention specifically in the text the work of only a few of the authors listed in the bibliography. The immense task of verifying all of the references in the bibliography has been accomplished only through the assistance of Mr. Robert J. Usher, Mr. William L. Teal, Miss Beryl L. Kanagy and INIiss Hazel B. Kraft and I desire to express my thanks for their invaluable help. I wish also to express at this time my appreciation of the great kind- ness of several of my colleagues and friends. Dr. Paul Degrais and Dr. Bellot of Paris have generously loaned me the drawings of microscopic sections, taken from their own immense material, which are reproduced in this book. Dr. George Winchester has prepared the framework of the chapter on the collection and purification of the emanation for thera- peutic purposes. Mr. L. W. Taylor has made the schematic drawing of the emanation apparatus and has constructed the emanation decay table inserted in Chapter IV. Dr. C. H. Viol has loaned me the photograph of the Debierne-Duane-Failla emanation apparatus Avhich is reproduced in the book. He has also read over the sections on the physics of radium and made valuable suggestions. Mr. James Eglin has carried out the actual work involved in the experiments on the absorption of gamma radiations in water, and has made the mathematical calculations used in the contraction of the tables in the chapter on dosage. Miss A. B. Hepburn, formerly physicist in our laboratory and Mr. Melvin Mooney, the present physicist, have also made valuable suggestions relative to the physics of radium. I am also indebted to Mr. Mooney for the schematic di'awing of the electroscope. I wish to take this occasion to thank the pul)lishers for their kind and unfailing cooperation. It is hoped that the book may be of interest, not only to those actually engaged in radium therajiy, but to all physicians, and that it may serve as a reflex of the current practice in this branch of medicine. F. E. S. Chicago, March, 1922. CONTENTS CHAPTER I PAGE The Radioactive Substances 17 The Discovery of Radioactivity, 17; The Discovery of Polonium, Radium, Mesothorium, Radiothoiiiun and Ionium, 17; Transformation of the Radio- active Substances, 18 ; The Radioactive Families, 19. CHAPTER II Radiuji — Its Okicix axd Chemical Nature 21 Origin, 21; Uraninite and Carnotite, 21; The Chemical Nature of Radium, 22; The Occurrence of Radium in Nature, 22. CHAPTER III Radium Emaxatiox and Radioactive Deposit 24 The Decay of Radium into Radium Emanation, 24; The Absorption of Ra- dium Emanation Ijy Diilferent Substance.s, 24; The Decay of Radium Emana- tion into Radioactive Deposit, 25; The Radioactive Deposit, 26. CHAPTER IV The Teciixic of the Preparatiox of Radium Emanation for Therapeutic Use axd the Method of Measurixg Its Gamma Ray Activity ... 29 The Preparation of the Enmnation, 29; Measurement of the Gamma Ray Activity of Emanation Tubes, 3-5. CHAPTER V Tiuc Radiatioxs from Radium and Its Decay Products 40 Alpha Rays, 40; Beta Rays, 41; Gamma Rays, 41. CHAPTER \l Absorption axd Filtration of Rays 43 Absorption of Rays, 43; Filtration of Rays, 45. CHAPTER A^II The AusoKi'Tiox of Gamma Rays in Water' 49 First Oliservations of Intensities with First Type of Ionization Chamber, 53; Second Series of Observations with First Type of Ionization Chamber, 5t; First Observations of Intensities with the Second TyjJC of Ionization Cham- ber, 60 ; Second Series of Observations with the Second Type of Ionization Chamber, 64; Final Series of Oliservations with the Second Type of Ioniza- tion Chamber, 66. ("JIAPTER VIII rHVSK'AL AXD CHEMICAL EFFECTS OF RaDIUM RayS 69 Ionization of Gases, 69; Penetration of Opaque ^Matter, 69; Production of Heat, 70; Emission of Light, 71; Phosphorescence and Fluorescence, 71; Photographic Action, 71; Coloration of A'arious Sul)staiu-es, 71; Other Chemical KtTects, 72. 9 10 CONTENTS CHAPTER IX PAGE l>iOLO(;ic Effects of Kaduwi Rays 73 Ert'oots of Riidiuiii Rays on Living Cells, ".". ; Effects of the Rays on the Skin, 76; P^ffeets on the Sjjleen, Lymphatic Glands, and Bone Marrow, 80; Effects on the E'lood, 80; Ett'ects of the Rays on Connective Tissue, Muscle, and Cartilage, S2; Effects of the Rays on the Thyroid and Thymus Glands, 83; P]ffects of the Rays on tlie Stomach, Liver, Salivary Glands, Pancrease and Kidneys, 83; Effects of the Rays on the Testis and Ovary, 84; Effects of the Rays on the Nervous System, 84; E]ffects of the Rays on the Eye, 85; Effect on Blood-Making Organs, 86; The Method of Action of Radium Rays on Xormal Cells, S(; ; Eft'ects of the Different Types of Rays, 88. CHAPTER X r>iOLO(;ic Effects of Radium Rays CContinued) 90 Effects of Radium Rays on Malignant Cells, 90; Eft'ect of Rays on Human Carcinoma, 92; The Method of Action of Radium Rays on Malignant Cells, 97; llie Question of Stimulation of Tumor Growth by Insufficient Radiation, 98. CHAPTER XI The Radium Reaction 103 Surface Radiations, 10."!; Intratumoral Radiation, 107 CHAPTER XII Therapeutic Apparatus 109 Apparatus Containing Radium Salts, 109; Ajtparatus Containing Radium Emanation, 111; Apparatus for Using the Radioactive Deposit, 114. CHAPTER XIII Dos.voE 109 Surface Radiations, 116; Intratumoral Radiations, 144. CHAPTER XIV The Teciinic of Radiation 146 Surface Radiations, 146; Intratumoral Radiation. lo;l. CTLVPTER XV IiADiu:M 1.x Gexkiiaf. Sukc.euy 1'"'8 Malignant Tumors, 15S; The Treatment of Carciuoninta, 160; Sarcomata, 'Jl'S; I'.cnign Tunior<, 2K); Cli ionic Infections, 240. ClIArTKlJ XVI KAKir.M IX Gvnecolocy -41 Malignant Tumors, 241; Denign 'i'liuiois, 211; .Metritis and Endometritis, 244; Metrorrhagia and Meiiorrliagia not Due to Cancer or Fibroid, 244; Myojiathic Hemorrhage, 244. CHAPTER XVII Radium in Dermatoloov -I"> Malignant Tumors, 246; P.enign Tunuirs, 24(5; Chionic Infections, 284; In- flammatory and Granulomatous Infiltrations of Uncertain Nature, 286; Hypertrophies, 294; Neuroses of the Skin, 294; Disorders of the Appeiulages of the Skin, 295. CONTENTS 11 CHAPTER XVI rr PA OK KADIt'M IX Ol'lITIIALMOLOGY, OTOLOOY, RhIXOLCKIY AXP LaKYXGOI-OGY .... 297 Oplitli.-iliiHilo'iy, 297; Otology, 298; Rliinolooy, 29S ; Laiyiicrology, 29S. CIIAl'TKR XLV RADlTUr IX DiSKASES OK THE DUCTLESS GlANDS ."'.O;', Loiikniii.'i, .'lO:',; TTodokin's Disease (LynipIi;ul('iioiii;)\ I'.nx ; (filler, .".OS; Kn- l;ir[ IX TxTEKXAL ^[EPirixE mo The Administration and lOliMiinaliini df Radium, .11(1; Plivsioloyii' EITccts of Radium, Hlo; IMorplioloyic Changes in the Tissue <-'aused liy Radium, ."IKi; Tiierapeutic liidieations, 318. CHAPTER XXI PiLOFESSiONAL Ixjruii:.s Dte to Radit'm 322 Local Etleets, :!22 ; Coiistiliilinnal EfVects, ;;22. BIBLIOGRAPHY BrHLIOGKAPHY . . 325 ILLUSTRATIONS FIG. PAGE 1. DoV)ieiii('-Duaiic-F;nlla nppnratus :?() 2. Diagranunatie iilan of apparatus in F\g. 1 I'l o. Diagram of elect roseope •'''•> 4. Diagi-ain sliowing olci-trical coiiiuH-tidns for mill mctlioil of using iouization chambor •">^ .1. Diagram of first type of ionization chambor -"l fi. Diagram of ajiparatus use;! 5. Graph showing intensity in water. Base of applicator :i cm. above surface .'4 9. Graph showing intensity below surface of water. ]?ase of apjilicalor (i cm. above water ^^•> 10. Gra]ih .showing tieUl •") cm. below surface of water. Base of api)licator 1 cm. above water -"'j 11. Graph sliowiiig fiehl 111 cm. below surface of water. Base of applicator 1 cm. from water o7 12. Gra])h showing field b") cm. below surface of water. T^.ase of ajiplicator 1 cm. from water o8 1?>. Grajih showing intensity on siirface of water. Base of ajiplicatdf 1 cm. from water .... ")!> 1-t. Grai)h showing intensity on sui-face of water. Rase o\' a[i]ilicator 1 cm. from water (iO 1.3. Graph showing field in air (il 16. Graph showing field in air, perpendicular to plane of tubes ()2 17. Graj)]! showing field in water, ])erpendicular to plane of tulies . . ... (U IS. Diagram showing change in intensity due to distance as com])ared with change in intensity due to absorption in water 07 19. Apparatus for the application of radium 100 20. Appartus for the application of radium emanation 11.3 21. Diagram showing two radium tul)es affecting three diftVrt'iit jioints on skin 122 22. Graph illustrating Table XXA'II . . . .' i:U 2.3. Diagram illustrating multiple ])ortals of entry 1.3(i 24. Photograph showing the method of handling radium 146 2.'5. Forceps 80 cm. long for handling radium tubes .... 147 26. Three pronged forceps 30 cm. long for handling radium tubes 147 27. Author's forceps for wrapjiing radium tubes in rubber dam 14S 28. Screen holders 140 29. Same apparatus as in Fig. 28 but of smaller size . . , 140 30. Flat silver screens with caps, devised for liolding from 2 to 6 enamel emana- tion tubes 1.30 31. Tandem gold screens for holding one or more enamel emanation tubes . . . 1.31 32. Platinum screen for containing a glass emanation tube 131 33. Screen for inserting radium tubes into the esophagus 131 34. Radium pad composed of "squares" of soft wood 132 35. Needle holder devised by Dr. O. T. Freer 133 36. Author's instrument, constructed on the plan of an ordinary syringe, for burj'ing emanation ampoules 133 37. Heavy cast-iron movable shield for the protection of the operator . . . . 134 38. Epithelioma of right cheek 162 .30. Patient in Fig. 38 after radivini tri>atuH'ul 163 40. Epitheliomia of right side of nose 164 41. Patient in Fig. 40 after radium treatment 16.3 42. Epithelioma of tip of nose l''*i 'b3. Patient in Fig. 42 after radium treatnu'iit 167 44. Epithelioma of left lower eyelid ^6s; 45. Patient in Fig. 44 after radium treatment T'!^ 46. p]pithelioma of right inner canthus, eyelids and nose 170 47. Patient in Fig. 46 after radium treatment 1"! 48. Epithelioma of left inner canthus, eyelids, nose, cheek, and upjier lip . . . 172 40. Patient in Fig. 48 after radium treatment 1"-"^ 30. Epithelioma of the right temide 174 31. Patient in Fig. 30, .-ifter radium 1 reatmeut !"•'» 13 14 ILLUSTRATIONS FIG. PAGE 52. Epithelioma ot tlio left toiniile 176 53. Patient in Fig. 52 after radinm trentnieiit 177 54. Epithelioma of left malar region 178 55. Patient in Fig" 54 after rndiiim treatment 179 50. Epithelioma of forehead 180 57. Patient in Fig. 5fi after radium treatment 181 58. Epithelioma of right ear 182 59. Patient in Fig. 58 after radium treatment 18.3 60. Epithelioma situated below right ear and involving ear !ol)e 184 01. Patient in Fig. 60 after radium treatment 185 62. Epithelioma of nose, left eyelid, cheek, and upper lip . 186 03. Patient in Fig. 62 after radium treatment 187 64. Epithelioma of lower lip 190 ()5. Patient in Fig. 64 after radium treatment 191 t)6. Epithelioma of upper lip . . 192 67. Patient in Fig. 66 after radium treatment 19.3 08. Epithelioma supervening on leukoplakia of right cheek . 194 69. Patient in Fig. 68 after radium treatment 195 70. Carcinoma of the tongue jn patient aged 65 years 196 71. Patient in previous figure after insertion of 19 niillicuries of radium emana- tion continued in 15 bare glass ampoules 197 72. Carcinoma of right superior maxilla involving antrum 200 7.3. Patient in Fig. 72 after radium ti'eatment 201 74. Adenoepithelioma of the prostate 209 75. Same lesion as in Fig. 74 after radium treatment . . 210 76. Carcinoma of the breast after powerful radiation 21,3 77. Portion of Fig. 76 at higher magnification 214 78. Portion of Fig. 76 at higher magnification 214 79. Atypic cubical epithelioma of the breast, before radiiition 215 80. A part of Fig. 79 highly magnified 216 81. Same epithelioma as in Fig. 79, after radiation 217 82. A part of Fig. 81 highly magnified 218 83. Carcinoma of loft breast 219 84. Patient in Fig. S3 showing improvement under radium treatment .... 220 85. Metatypic pavement cell epithelioma of the neck of the uterus. Before treatment 222 86. Same epithelioma as in Fig. 85. Fragnuuit removed 10 days after the first application of radium 222 87. Same e]iithelioma as in Fig. 85. Section remo\ed on the 29th day after the first radiation 223 88. Same epithelioma as in Fig. 85. Fraginent removed from the surface of tlie cicatrix of the neck of the uterus th.ree months after first radiation . . 224 S9. Polvnior]ihous sarcoma with ]ired()niinance of fusiform cells. P>efore radia- 'tion 228 9(1. Same sarcoma as in Fig. 89. Section of large nodule iemov(>d 15 days after powerful irradiations 220 91. Same sarcoma as in Fig. 89. After radiatidu 230 92. Sarcoma of right ear. Recurrence after excision 231 93. Patient in Fig. 92 after radium treatment . . . . 231 94. Sarcoma of left cheek in girl aged nineteen . . 232 95. Patient in Fig. 94 after ladium treatment . . ... 233 96. .Tumors of eyelids 234 97. Patient in Fig. 96 after radium treatment 235 98. Sai'coma of bone. RecurieiU'c after operation 236 99. Patient in Fig. 98 after ladiuni treatment 237 100. Lym))hosarcoma of neck 238 101. Patient in Fig. 100 after radium treatment 2.39 102. Cicatricial keloid, following a burn of the face. T'>efore ladialidii . ' . . 246 J 03. Same keloid as in Fig. 102 after radiation 247 104. Keloid of right great toe 248 105. Patient in Fig. 104 after radium treatment 248 106. Keloid of back due to burn from a flat-iion 250 107. I'atient in Fig. 106 after radium treatment 251 108. Keloid of back of neck. Recurrence after surgical i-enioval 252 ILLUSTRATIONS 15 FIG. ^ PAGE 109. I'aticiit in Fig. 108 :iftei- ladiuin tiontiiuTit o-y_> 110. "Acne keloid'' of hack of neck .... "54 111. Patient in Ficj. 110 after i-adiuni treatment .... . '>55 112. Keloid of face following a burn 9.3^ 11.3. Patient in Fig. Ill' after radium treatment ... 257 114. Flat angioma of the hairy surface. Before radiation 258 115. Same angioma a.s in Fig. 114, after treatment with radium liy tlie metjiod of "selective reaction," i.e., without visible macroscopiv- inflammatiuii . . 259 11(1. Cavernous angioma of tip of nose 200 117. Patient in Fig. 116 after radium treatment ... 200 lis. Cavernous angioma of forehead 201 119. Patient in Fig. 118 after radiun; treatment 261 120. Cavernous angioma of lower lip 202 121. Patient in Fig. 120 after radium treatment 20;; 122. Flat angioma of side of face, neck, cliin, and hiv^iM- lip 264 12.3. Patient in Fig. 122 after radium treat nn'ut 265 124. Vascular nevus of face and neck 206 125. Patient in Fig. 124 after radium treatment ... 260 120. Angioma of side of face and head in jiatient aged six weeks 267 127. Patient in Fig. 126 at age of one and one-half years, after radium treatment 267 128. Slightly elevated angioma of side of face 268 129. Patient in Fig. 128 after radium treatment 269 180. Angio.sarcoma (?) of left arm 270 1.31. Patient in Fig. 130 after radium treatment 271 132. Large cutaneous and subcutaneous angioma of left side of neck in child aged months 272 13.3. Patient in Fig. 132 after radium treatment 272 134. Lymphangioma circnmsciijitum of right Imttock and inner surface of rii'lit thigh 275 135. Patient in Fig. 134 after radium treatment 275 136. Pigmented nevus of left lower eyelid and face 276 137. Patient in Fig. 136 after radium treatment 277 138. Pigmented hairy nevus of left eyebrow and forehe;id 278 139. Patient in Fig. 138 after radium treatment 278 140. Linear nevus in patient aged 4 years 279 141. Patient in Fig. 140 after radium treatment 279 142. Tuberculosis verrucosa cutis of first phalanx of left middle lin;;er .... 280 143. Patient in Fig. 142 after radium treatment 280 144. Tuberculosis verrucosa cutis of first phalanx of left Tlnuiib 281 145. Patient in Fig. 144 after radium treatment 281 140. Lupus vulgaris of right cheek in girl aged thirteen 282 147. Patient in Fig. 146 after radium treatment 283 148. Lupus vulgaris of right cheek 284 149. Patient in Fig. 148 after radium treatment 285 150. Blastomycosis of left inner canthns 286 i51. Patient in Fig. 150 after radium treatment 286 152. Lupus erythematosus of nose and cheeks 287 153. Patient in Fig. 152 after radium treatment 287 154. Lupu.s erythematosus involving nose and cheeks 288 155. Patient in Fig. 154 after radium treatment 289 156. Lupus erythematosus involving right cheek and u]t])er li|i 290 157. Patient in Fig. 150 after radium treatment 291 158. Lupus erythematosus of four years' duration 292 159. Patient in Fig. 158 after radium treatment . . 293 1()0. Syco.sis vulgaris 296 101. Patient in Fig. 100 after removal of hair with radium 290 102. The Freer clani]) for the intralaryngeal aiMtlication of radium 300 103. The applicator held in the jaws of the Freer rlami) with the screen contain- ing radium emanation in the glottis as indicated by heavy dotted lines . 300 164. Ap]iaratus for intralaiyngeai radiation .... 301 105. Chroni'- lym]iliatic leukemia 304 10(). Patient in Fig. 1()5 showing leniission of the disease after radium tnatment 305 RADIUM THERAPY CHAPTER I TTTE RADTOACTTVE SUBSTANCES THE DISCOVERY OF RADIOACTIVITY Soon after IvDcnliicn's discovery in lSi)5 of the x-rays, several physi- cists ])eo'an to experiment willi \;irioiis snl)stanees to determine Avliether similar rays mijzlit l)e emitted l)y elieiiiieal Ixxlies spontnneously. Poin- eare suggested that tlie production of x-rays, wliieli peneti'ated matter opaque to ordinary light, might be connected witli the phosphorescence and fluorescence excited l)y tlie cathode rays in tlie glass of tlie vacuum tuhe. It was natural at first, therefore, to examine substances that fluoresced under the action of ordinary liglit. Prof. Henri Becquerel of Paris soon found that the fliun-escent salts of ui'anium emitted radiations that passed through a tliin layor of silvei- and affected a ])hotograi)hic plate. It was at first supposed that the emission of these peculiar radia- tions was in sonu' way connected with tlie fluorescent properties exhibited by some of the uranium com|iounds. Further experiments proved, how- ever, that tlie nonfluorescent salts and the metal uranium itself, Avliich is also nonfluorescent, emitted the radiations. From this observation Prof. Becquerel concluded tlnit the rays were due to the element ui-anium and were independent of phosphorescence or fluorescence. The announce- ment of this new property of matter — so-called radioactivity— was made to the Academy of Sciences at Paris on February 24, 1896. Later Prof. iJecquerel showed that uranium radiations like x-rays were capable of discharging electrified bodies such as the electroscope. Rutherford, in 1890, demonstrated that this effect was du,' to the " ionization" of the air in th(> electroscope by the radiations. This phenomenon will be re- feri-ed to more fully in our description of the method of nu>asui'ing the gannna-ray activit\" of I'jidium. THE DISCOVERY OF POLONIUM, RADIUM, MESOTHORIUM RADIOTHORIUM AND IONIUM Using the electrosc(»])ic method of investigation, different physicists then examined vai-ious othei' substances in order to determine whether they were radioactive. (I. ('. Schmidt and ^liiie. Curie, working iiule- 17 18 RADIUM THERAPY peiidently, discovered in 1898 that thorium, an element derived from monazite and previously well known, possessed radioactive properties. ]\r. and Mme. Curie then found that certain uranium ores exhibited a greater degree of radioactivity than could be accounted for by the pres- ence of either uranium or thorium. They assumed, therefore, that some unknown element or elements Avere present in the ores. Their labors finally resulted in the discovery of polonium which was named from Mme. Curie's native land, and later (1898) of radium. Polonium is now known to be merely Radium F., one of the decay products of radium itself. In 1900, Debierne obtained from i)itchl)lende another radioactive product which he called "actinium" and in 1905 Hahn isolated mesothor- ium and radiothorium. Ionium was discovered in 1907 l)y Boltwood. Al- together more than 30 radioactive substances arc ii(»\v known. TRANSFORMATION OF THE RADIOACTIVE SUBSTANCES It was at first supposed that the radioactivity of uranium, thorium and radium was a permanent attribute. Later, evidence of the decay and recovery of radioactivity was noted. Now all accept the hypothesis first advanced by Rutherford and Soddy which explains radioactivity as a spontaneous process of atomic transformation. This process goes on at a regular rate for each radioactive substance and is accompanied by the emission of rays and the production of new forms of matter, these new elements in time transforming, until finally a stable atomic form is reached. These changes go on with greatly varying degrees of rapidity. Some of the radioactive l)odies are transforming themselves so slowly that no change in their radioactivity can V)e detected over a period of several years. Their radioactivity, thei-efore, is relatively constant. To this group belong uranium, ionium, I'adium and thorium. Other radioactive bodies, of which mesolhorium 2 and thorium X are examples, transform themselves very (piickly and cease to emit rays after a few hours or days. Tlie rat? of transmutation is cf)iistant for any given substance, but differs for the different radio-elements. The rale at which a substance decays follows an exponential hiw; i.e., the rate at which a substance is decaying at a given in.stant is ))roi)ortioiial to the amount present at that instant. It is this factor of proportioiudity that is constant for any ijarticular substance. The rate of loss of activity is usually spoken of in terms of the "period," or moi-e properly the "half decay period" both expres- sions being used in an identical manner. The period of radium is ap- proximately 1680 years. I>y this is meant that after 1680 years, one half of tlie original number of atoms remains untransformed ; after 3360 years (2.\1680) one fourth remains; after 5040 years (3x1680) one eighth I'cmains, and so on indcfinilcly. Radioactive t I'ansforinations differ from ordinarv chemical reactions in that the rate of degeneration or change KADIOACTIVF, i^rBSTAXCKS 19 ol' one radioactive substance into another cannot he altered by any known physical or chemical means. The rate of transformation remains the same ihrou^houl exti'cmes of lenipei-ature and pressure. As each radio- active substance t I'aiisforins, it liix'cs off radiations. Avhicli arc of three ditl'eirnt kinds and ai-c known as al|)ha, beta and 'e of the fact that actinium and its (b'cay ])roducts are always present in uranium miiuu-als. lends to the belief that this product represents a small fraction (8 per cent) of the "ui-anium 2" atoms which transform into "uranium Y" i-athei- tlmn into ionium. We uuiy interpolate a table at this point showing' the nu-mbers of each sei-ies of i-adioactive bodies, the raj's each substance emits ami its half value, i.e., the tinu' re(|uii'ed for ^. of a eta+j^amma Kadiiim C 214 19.5 minutes beta l-gamma (9i».{)7%) (0.().'i%) (alpha) Kadiiim C 210 1.4 minutes beta+gamma (side "road idii ().(i;!%) End 0.0.3% 210 214 Radium C 0.000(1(11 seeoiids .•ilplia ( .^^ain i-cart 1(111 Itll.il?';/ ) I{:idiiim 1) 210 1(3.5 years soft lieta Radium J-] 210 5.0 days soft beta Radium Y ( I'ldoniiim ) 210 1.36 ranis (three metric tons) of metallic urainum there is oiu^ i"ation theory of Tiutherford and Soddy. accordiuu' to wliicli uranium is the i)ai"ent of radium. Tn uranium-coutainin- minerals ai'e kiU)wn. (udy two are of jiraetical im])ortaiU'e. These are uraniuite and earnotite. Tn these ores, radium occui-s in workable quantities. I"''raniuite is fouiui in liohemia, ( '(U'nwall. ("oloi'ado and nuinx' other localities. This mineral occurs chiefly in an amorphous nmditication known as pitchblende, a dense black substance of variable comiiosition and therefore not to be described by a siuo'le chemical f(U-mida. Pitidi- bleiule is essentially an oxiesi(les occui-ring in moi'e or less concentrated t'orui in various ores, radium is round throniihont the earth's ci'ust as one of the most widely distributed of snhstanees. Strutt, doly. Knocke, and others have de- tected it in minute (|ii;int it ies in volcanic rorks and in sea and riv(>r waters. KADIIM OKMCIX AND CIIK.MK AL XATIKE 2.'^ As to the natural oecurrcMK-e of radium in the animal and vog'etablc tissues, experiments have ])een made by Lazarus-Bai-low, Beeijuerel and othei's to determine tliis jxiint. K\ideiu'e has been pi-esented to show- that radium in ver,\ ininute (luantities, but detectable by the electro- scope, exists in human tissues. La/.arus-liarlow has sought to show tliat in human tissues att'eeted by maliuiuint disease a slightly larger ({uantity is present than in noi-mal tissues. This hypothesis cannot be considered as establishetl. anil since no radium salt is absolutely insol- uble, it is difficult to reconcile the concentration of radium in a tissue with any hypothesis that does not also involve the simultaneous increase in concentration of other elements such as calcium and magnesium, and if this be true, their chemical efit'ects must also be considered. Prof. Becquerel concluded that if radium oi- any other I'adioactive sub- stance exists in plants, it is in such small (luanlities as to have no ap- preciable effect on their growth. CHAPTER III RADIUM EMANATION AND RADIOACTIVE DEPOSIT THE DECAY OF RADIUM INTO RADIUM EMANATION As has been previously said, radium atoms, like those of the other radioactive bodies, are not absolutely stable, but are constantly trans- forming- and g-ivini;i'OSlT 'J") liiiiuids liavc \;iryiii^ ])()\\('rs of al)soi-l)iii;i' llic cinaiiation. Fresh water absor]).s moro than salt water, while org-anie ]i(|ui(ls al)s(irl) it more readily than eithei-. Tt was found by Rauscli xon Tranhenh'T^' that if air conlainin'.'' emana- tion was shaken up willi watei', the air and the water eaeh soon contained a definite proportion oi' the emanation. In tliis res])ect the emanation follows TTeni'v's law, for it is absoi-hed until a state of eiiuilibrium is reached between the pressure of the emanation in the Avater and in the p:as. The term "eoeffieient of absorption" has been used to express the extent to Avhieh the emanation is soluble in litpiids. This term may be defined as the ratio between the concentration of the emanation in the liquid and in the fjas after equilibrium has been reached. The value of this coefficient may be determined experimentally by the method of von Traubeid)ei-' up the liquid and the ^'as containing the emanation, and then measurin H ADIOACTIVK DKI'OSIT 27 posit lli;il llic luhc should coiilaiii radiiiiii a1 all. If llic radium ciiiaiia- tion alone is introduced into the tuhe and Ihe tul)(> is sealed, the active deposit is formed in preeisely the same manner. When tlie emanation has aU decayed, the ae1i\-e dejxisit of course ceases to foi'm and the radioactivity of tlu' tube is at an end so far as its therapeutic efficiency is concerned. As a mailer of fact, radium 1). V] ami !■' are still contained in the tube, l)ut as theii- t rausfornuil ion is vci-y slow, and as the oamnni rays ]ii'o(luced by lliem ai'e of feeble iiileiisily, lliese pi'oducls are not of therapeutic interest so fai' as the local application of radium is con- cerned. The Atomic Disintegration Theory of Rutherford and Soddy The disintejiralion theory of Kntherford and Soddy explains in a ra- tional manner the transfoi'mation \vhi(di radium and the other radio- active substaiu-es under<>'(). According to this theory substances exist in nature whose atoms, unlike those of most elements, are not stable hut are constantly undergoino' siionlaneous disinteoration. These are known as radioactive substances. The rapid disintegi-ation oi- "explosion" of the atoms of such substances results in a rearrangement of the electrons comjiosing the atom-. In a given lime a certain definite proportion of all the atoms of a radioactixc substance becomes unstable and breaks up. An alpha particle or i-ay oi' Ix'ta and gamma rays are given off in the process of disintegration. In a \'rw cases, as in the case of actinium, which transmutes into radioactinium. disintegration of the atom ap]iar- (Mitly takes place without rays being given off. Thci'e is chemical evidence that leads to the belief Ihat in these "rayless" changes ther(» is really emitted a low speed beta i-ay which because of its low velocity esca])es detection. AVheii an alpha pai'ticle is gixcn ofT. as a conse((uence of the disintegration of the atom, the i-esidting atom is always lighter than its predecessor and possesses diffei'eiit i)hysical and (dunnical properties. This is ^\■ell illust i'ate(l by i-adium ami its next t rausfoi-nuif ion i)roduet, radium emanation, Mliich arc s1i-ikingl\' dissimilar, as we ha\e seen. From this \ie\\|)oint. we may now consider the bi'caking up of the radium atom to form the i-adiuin emanation atom, of the radium emana- tion atom to foi-iii the atom of I'adiuiii A, etc. In the i-adium series there are 5 substances that gi\'e off alpha ])afti(des (helium atoms) as they disintegrate. These ai-e. in order of occni-i'cnce, Kadium, Eadium emaiuition, l\adium A, Radium (', and Radium F. Assuming the atomic weight of radium to be 22(i and that of helium to be 4, the final atom l)roduced when Radium F disintegrates should have an atomic Aveight of 22B less 20 (i.e., 5 x 4) or 2()(i. This is slightly less than the atomic weight of lead and it is an isotojie of this nu'tal that is the final product in the radium disintegration series, in Table I\' this point is made clear and certain other data are given for reference. 28 RADIUM THERAPY Table IV RADIUM ATOMIC WEIGHT PER HALF-VALUE RADIATION RANGE OF SERIES WEIGHT GRAM OF PEraoD ALPHA RAYS RADIUM AT 15° C. Radium 22G 1 gram 16.80 years alpha 3.30 cm. ' Radium 1 Emanalion 222 5.7x10-6 gram 3.85 days alpha 4.16 cm. Radium A 218 3.1x10-9 gram .3.0 minutes alplia 4.75 cm. Radium B 214 211 2.7x10-8 gram 2.0xl0-s gram 26.8 minutes 19.0 luiiiutes Ijeta-l-gamma beta-l-gamma Radium C 6.57 cm. (alplia) Radium '^ 210 1.1 minutes 16..J years 5.0 days 1.36 davs betafgamma soft beta Radium D 8.0x10-^ gram 210 7.1x10-6 gram 1.9x10-4 gram soft beta Radium F 210 alpha 3.77 cm. 20G No rays Atoms stable (End Product) CHAPTER lY TTTE TECHXIC OF THE PREPARATION OF RADrT':\r E:\rA\ATIOX FOR THERAPET^Tir USE AND THE :\rETTTOD OF :\rEAS- T^RTxr; TT?i OA:\r:\rA ray aottytty THE PREPARATION OF THE EMANATION Radium omanatioii in lubes or applicators instead of the radium itself as a souree of tlierapeiitie radiations appears to have been used first in 1912 by the London Radium Institute. The Bebierne-Buane apparatus (Fior. 1) ns modified by Failla of X^ew York is used by the -writer for the extraction, purification, and concentration of the emanation. This apparatus consists essentially of two modified mercury pumps of the Toepler type, familiar to ])hysicists. Tlie fii-st ])uiii]i draws the accumu- lated jSfases from the flask containino- the radium solution and introduces them into the purification chamber. The second pump withdraws the l^ui'ified emanation and concentrates it in a capillary olass tube. The radium in the form of radium chloride is dissolved in about two ounces of -water to which has been added a small amount of dilute hydrocldorie acid to ]irevent precipitation of the salt, h'roni a ]iractical point of view not less than ^/o gram of radium element can bo utilized economically in this manner. The oliiss flask containing the radium solution is kept in a suitable p.afe, and rests in a i^orcelain lined lead vessel in order to minimize the possibility of loss. The radium flask is not shown in the diagram but is connected by means of a glass tube (J, Fig. 2) to tlu^ i)umping system of the emanation apparatus as shown in Fig. 2. Ye.'-.sel 4 (Fig. 2) is ordinarily kept partly filled with mercury in order to prevent the entrance of emanation. If the emanation were allowed to stand in lliis vessel it would cover the walls with the active deposit and since the surface of the vessel is quite large, the ojierator would find it necessary to shield himself from the bombardment of the rays. The emanation that is formed by the disintegration of the radium is not the oidy gas formed in the solution. The radium rays, continually l)ombarding the water molecules, cause a decom])osition of the water into its constituents, hydrogen and oxygen. These two gases form by far the largest ]);iit of all the gases produced. The total volume of all the different gases is numy times the volume of the enumation. In order to concentrate the emanation into a small volume at a i^ressure of, e.g., 20 cm. of mcn'cury. the foi'cign gases must, for the most ])ai't. be removed. In order to accomplish this, all the gases in the radium flask are ])nm]ied 29 30 RADIT^M THERAPY over into the piirificatioii chamber 9, 10, and 11, Fig. 2. Here the sodium hydroxide {9), and phosphorus pentoxide (11) absorh carbon dioxide, moisture, etc., while the heated copper oxide spiral (10) causes the hydro- P'ig. 1. — I'hotograph of iH-bierne-l Juane-Failla apparatus. Tlit- pliotdRiapli shows tlit- siiiRle type of apparatus. The duplex type is usually installed so tliat cither side of the system may l)e availahle in ease of accident. gen and oxygen to recoml)ine. Tlu' piiriticd emanation is then made to pass into vessel 12, being finally compressed in the tube at cock 16. It is then forced out into the cnpilbiry glass tube IS. The distal portion PREPARATION' OP RAHUM E.MAXATIOX 31 (1 or more cm., e.g.) of this tube C'Oiit;uiiiii<>- the concentrated emana- tion is tlien cut off })y a minute oa.s flame. The mechanical details of the process are as follows: The auxiliary vacuum pump that is attached to vessel 25 is started and stopcocks 22 and 8 are opeued in order to create a A-acuum in the line 8-22 above the mercury in vessel 7. Stopcock 6 is now opened and the mercury in 4 falls to the level in 7. This allows the emanation, hydrojicn, oxygen, ozone and water va])or to come out of the radium flask through tube 1 aud to fill 4 by diffusion. Cock 22 is now turned to permit air to enter the line 8-22 through the drying tube 23 containiny' calcium chloride. This forces the mercury up in i, driving the gases ahead of it and past the l"i<<. 2. — Diagriimir ,'itic j>l;iii nf a|i]iaraliis in I'isr. 1. trap .7 intct tlic purification cliaiiihei- {!), JO and //). Cock 22 is again tui'iied 1o coinicd the liiu' 8-22 with llic auxiliiii'v pmii|) and llic mercury in i again falls, allowing another jiortion of the accumulated gases to fill the bulb. The mercui-y in Irap .7 pre\-ents the backward i>assage of gases fconi !), 10, 11 1() /. This ])i'(H'ednre of (illiiig /' with the gases aiul foil- ing them up past the tra]) .V into tlie purification chaml)er is repeated until all the gases are pumped o\"e!'. The completion of tlie i)rocess is easily detected hy the fact that when tiiei-e is no gas present, the rising mercury in / pi'oduces a sharp metallic click when it sti'ikes the mercury in trap V. Hefoi'c the ])umpiiig i)i'oeess just described is started, the ])urificati()U chamber ( />, 10 and //) is tested to insure the existence therein of a good 32 RADIT'M THERAPY vacuum. If gases are found to he i^resent, they tire pumped throuorh 16 and 17 into 26 by means of the mercury pump 12, 13, 14 and 15. From there tlu'v may he exhausted into the room through 24 by the auxiliary ]iunip and thence out of tlie I'oom by means of a ventilating fan. When a high vacuum lias l)een established in the purification chamber, an electric current is sent tlii-ough the copper oxide coil 10, the strength of this current being just sufficient to bring the coil to a low dull-red heat. AVhen the coil is hot, tlu' jnirification chamlx'r is ready to receive the gases from 4. As they meet the hot coil, tlu' hydi-ogen and oxygen reunite and form water which is immediately absorbed by the phos- pliorus pentoxide (P.0-) contained in 11. IJy this actiori most of the gas entering the purification chamlier is eliminated. If any carbon dioxide, chlorine or hydrogen chloride are ])resent, they are absorbed l)y the sodium hydroxide in .'). Thus by the time all the gases are pumped out of the radium flask into .9, 10, 11, consuming, let us say one hour of time, there is little left in the purification chamber except helium and the radium emanation itself, all other gases having been absorbed. The emanation is now ready to be pumped over into the capillary tube 18. With the line 8-22 at atmospheric pressure, stopcock 20 is opened and the mercury is allowed to rise a fcAV centimeters in the y-shaped tube above 19 to prevent communication between 17 and 26. During the purification process the bulb 12 is left partly filled with mercury in order to prevent its being filled with the gases that are to l)e purified. With a vacuum in the line 8-22, stopcock 14 is opened, the mercury falls in 12 and the emanation, expanding from the purification chamber, fills this bulb. Stopcock 22 is uoav turned to connect line 8-22 with atmos- pheric pressure. This causes the mercury to I'ise in 12 and as it nears the top of the bulb, stopcock 16 is opened and the emanation is forced out into 17 by running the mercury about 1 centimeter past 16. Stopcocks // and 16 arc Iheii closed. Line 8-22 is again exiiausted, stopcock 14 is reopened, and llic mercury falls out of 12 which is again filled Avitli emanation, in this manner ]n'actically all of the emanation may be ))umped over into 17. When the mci-cury lias been raised in 12 for Ihc last time it is allowed to ])ass tlirough 16 and uj) to 17. The emanation is then forced by means of the mercury in ;.'/, by opening stopcock 20, into the capillary tube 18. The mercury rises in the capillary and when the dcsii-cd concentration is effected, stopcock ^0 is closed. The capillary glass tube is about 1 millimeter in diaJiieteT'. and can be sealed off very readily ])y means of a small pin-hole gas Ihinic. The pai't of Ihc capillai-y 1ul)c sealed off con- taining all the emanation is then divided by means of the same flame into as man\- j)ieces as arc desired. Tn this manner, any percentage of the total amount of emanalion is ol)tainc(l for use in a small lube, of, e.g., 1 centimeter length. These small glass lubes arc then inserted into o mill 5 10 20 30 40 50 GO 1 hr. 30 mill. o 2 30 mill. 3 4 I'RKI'ARATION OF RADITM KM AN ATION 33 Table V Showing the Rise of Gamma Ray Activity due to RaC through 2 cm. of Lead TIME: activity of an emanation tube measured in PERCENTAGE OF MAXIMUM VALUE: — - .025 .32 1.90 8.9 19.0 30.0 41.2 51.3 74.4 87.8 94.7 98.0 99.9 enameled silver tubes the ends of Avhieh are blocked with paraffine. They are then set aside for 3i,{, hours before their aetivity is measured. The next day the same ])roeedui'e is repeated in order to withdraw and concentrate llic ciiuiiuilioii wliieh has acciiinulatcd in llic jii'eccdino- 24 hours. When the emanation is fii'st admilted to the capillary 1iibe its activity, measured by the penetrating rays, is zero. As the emanation decays, Table VI Showing the Rate of Decay of Radium Emanation TIME percentage OF MAXIMUM ACTIVITY (THEORETICAL) 100.00 1 lir. 99.25 2 lirs. 98.51 3 " 97.77 4 " 97.04 5 " 9G.32 G " 95.60 12 " 91.39 1 dny . 83.53 2 days 69.77 3 " 58.27 4 " 4S.68 5 " 40.66 G " 33.96 1 week 28.37 2 weeks 8.05 3 " 2.28 4 " 0.647 10 " 0.000337 34 RADIUM THERAPY however, the active products, Radium A, Radium B, and Radium C are formed, producing an invisible film on the walls of the tube. The pene- trating radiations from these products gradually increase until the tube reaches its maximum activity. This takes place aliout 4 hours after the emanation has been sealed in the capillary glass tube. The growth of the activity of Radium C with time is shown in Table V. About one hour after the maximum value of the gamma radiation has been readied, the activity of the tu])e begins to decay with the same "time period" as that of the emanation. In other words, K) per cent of the activity is lost every 24 hours. The activity at any given time will be reduced to ^, the value at that time after 3.85 days have elapsed. Table VII shoAvs the calculated decay of radium emanation tubes from day to day. For example: Let us find the number 78 in the single left Table VII Eadium Emanation Decay Table 1 1 2 3 1 2 3 1 2 3 90 75 63 52 60 50 42 35 30 25 21 17 89 74 62 52 59 49 41 34 29 24 20 17 ■ 88 74 61 51 58 48 40 34 28 23 20 16 87 7.'> 61 51 57 48 40 33 27 23 19 16 86 72 60 50 56 47 39 33' 26 22 18 15 85 71 59 50 55 46 38 32 25 21 17 15 8i 70 59 49 54 45 38 31 24 20 17 14 83 69 58 48 53 44 37 31 23 19 16 13 82 69 57 48 52 43 36 30 22 18 15 13 SI 68 57 47 51 43 36 30 21 18 15 12 80 67 56 47 50 42 35 29 20 17 14 12 79 66 55 46 49 41 34 29 19 16 13 11 78 6.1 54 45 48 40 34 28 18 15 13 10 77 in 54 45 47 39 33 27 17 14 12 10 7G 64 53 44 46 38 32 27 16 13 11 9 ^ 7.1 63 52 44 45 38 31 26 15 13 10 9 74 62 52 43 44 37 31 26 14 12 10 8 7.*^ 61 51 43 43 36 30 25 13 11 9 8 72 ()0 50 42 42 35 29 24 12 10 8 7 71 59 50 41 41 34 29 24 11 9 8 6 70 59 49 41 40 33 28 23 10 8 7 6 69 58 48 40 39 33 27 Oo 9 8 6 5 68 57 47 40 38 32 27 22 8 7 6 5 67 56 47 39 37 31 26 Of) 7 6 5 4 66 55 46 38 36 30 25 21 6 5 4 3 65 54 45 38 35 29 24 20 5 4 3 3 64 5.3 45 37 34 28 24 20 4 3 3 2 63 53 44 37 33 27 23 19 3 3 2 2 62 52 43 36 Ijo 27 23 19 9 2 1 1 61 51 43 36 31 26 22 IS 1 1 1 60 50 42 35 30 25 21 17 PREPARATION OF IfAlHIM 1:MAXATI0X 35 hand vertical poluiiiii. A liihc lia\iii: horizon- tally to the riji'ht. By findiiiasily absorbable rays. II is a metal box containing the gold leaf system. When the system is charged through C, e.g., with positive electricity, the gold leaf, which in the uncharged condition hangs vertically, is forced out into a partially hoi'izontal ]>osition being thus brought into the field of the microscope, I). In order to measure the i|uantily ol' a radioactive substance in a small capillary tube, the bitter is placed in the \'-sha|)(Ml holder at E. The l>enetrating gamnui rays then ])ass through the lead plate, .1, into the electroscope, 7?. and the air in the electroscope is thus nuide a conductor of electricity. This is known as "ionizing" the air. In other A\ords, the radium rays generate small positive and negative "ions'" or charges of electricity in the air. If the gold leaf is charged positively, it will attract the negative charges to itsell". The negative charges will thus neutralize a i)art of the positive charges of the leaf. Tlic leaf will then tend to come 36 RADIUM THERAPY nearer into the uiicharoed or vertical position and will tlnis move across the field of tlie microscope. The rate of this motion is a measure of the number of "ions" formed per second in the air, and this in turn indicates the intensity of gamma or penetrating; rays from tlie emanation tube. The larger the amount of emanation in the tube at E, the faster will be the movement of the gold leaf across the scale in the field of the microscope. The rate of motion of the leaf is ordinarily timed by means of a stop watch. In order to facilitate the use of the electroscope in measuring unknown quantities of radium emanation, it is necessary to have at hand a stand- ardized tube of radium. One then determines the rate of fall of the leaf in the electroscope caused by the known or standardized specimen. Men- tion may be made here of the International Radium Standard. This con- sists of 21.99 mg. of pure radium chloride containing 16.75 mg. radium element, which M^as prepared my Mme. Curie in 1910 at the request of the Brussels Congress of Radiology and Electi-icity. This was sealed in a glass tube and is kept at the International Bureau of Weights and Measures at Sevres, France. Other countries have standards as fol- loAvs: Austria, 31.17 mg., England, 21.13 mg., Germany, 19.73 mg., Japan, 9.80 mg., Portugal, 9.09 mg., Sweden, 9.73 mg., United States, 20.18 mg. The unit in which quantities of emanation are expressed is called the curie. This has been defined as the quantity of emanation in equilibrium with one gram of radium element. For practical purposes a smaller unit, the millicurie, ^Xooo of a curie, is used. The gamma ray activity of a millicurie corresponds to the gamma ray activity of one milligram of radium element. The microcurie is Yiooo of a millicurie and corre- sponds to one microgram of radium element. The number of milligrams of radium element in the "standardized" tube, divided by the number of millicuries of emanation in the unknown tube is equal to the ratio of the number of ions produced per second Avhen the "standard" and the emanation tube are successively placed at E. This last ratio is equal to the inverse ratio of the time of fall of the " " '^ ( sions under action of standard. /j = time of passajjo over same nunilter of scale divisions under action \ of emanation lulie. Let US suppose, for o.xainplo, tliat we liave as a "standard" a tube con- taining 15 milligrams of radium clement (the activity being therefore equivalent to that of 15 millieuries), and an uid^nown emanation tube, the activity of which is to be measured. The "standard" is placed at any convenient distance from the electroscope and the latter is charged, so that the leaf diverges. The time of passage of the leaf, e. g. 40 divisions, is observed. Let us assume this elapsed time to be 1 minute (a). The emanation tube is now suhslihilcd for the "standard" and a similar ob- servation taken. We will assume the time in this case to be 50 seconds (/>). Substituting in the above formula the values of s, a and /) which are now known we find E --^ 15 ^'^7-= 18 mc. M) It will be observed that, within certain limits, the distance of the "standard" and the emaiialioii lube fi-oni the electroscope during the cal- culation is immaterial. The number of scale divisions, over which the reading is made, is likewise unimportant. But whatever the distance or number of scale divisions chosen, observance of the following precautions is vital to the securing of (l(>pendable results: (1) The standard and the emanation tube must, in turn, be placed at exactly the same distance from the electroscope. (2) While readings are being made on one tube, the other tube should be placed 30 or 40 times as far away and preferably behind a heavy lead screen. (3) The same nuinliei- of scale divisions over the same region of the scale must be used in each reading. If, as has been suggested above, the rate of natural leak of the electroscope is sufficiently great to have an appreciable effect on tlie i-esulls, allowance for this must be made in the ealeulat iciis. In lliis case 1lie t'oi'iiiula takes the form: ah a- — e nh b- — c Here r is the time taken by the leaf when no tube is ])resent in passing over the iiumlier of scale divisions chosen I'or the readings. Let us sup- l)ose, as is the case in our laboratory, that this is of the order of 25 min- utes; tlu' foi'iiiuhi then becomes: RADIUM THERAPY ab 60 X 50 = 2 c 25 X 60 60 - 2 E = 15 X =18.13 50-2 This error (.13) (less than 1 ])er cent) for many purposes is negligible, at least in small tnbes, and. as a rule, iu cases similar to this the correction would not need to be made. But if the activity of the "standard" and the tube to be measured is not approximately the same, failure to make the correction wovild lead to a considerable error. For example, assuming s, a and c to have the same values as before, but assuming b = 10 seconds, then E = 60 15 X = = 90 (iiiicorrectccl) ah c ~ 60 X 10 - 25 X 60 = A E = 60- 1-5 x,„ A 93.12 10- .4 This would lead to an error of con.siderably over 3 per cent if the correction were not applied. T]ie Preparation of the Active Deposit. — As we have previously stated, it is sometimes desired to collect a quantity of active deposit on a sheet of metal foil. In order to accomplish this, a piece of lead foil of about 0.1 mm. thickness is rolled in such a way as to fit snugly into a glass tube, closed at one end. This tube, containing the foil, is then sealed in a vertical position, to the emanation apparatus at 17 instead of the usual capillary tube. (See Fig. 2). After the air has been pumped out, the purified emanation is forced into the tube by means of mercury raised to the lead foil. After 3 or 4 hours, when the maximum amount of active deposit has been formed and d('])osited on the foil, the mercury is lowered and the emanation allowed to pass into another part of the apparatus to be collected in the usual numner. AVhen the tube is cut off and the foil carefully removed, its activity may be measui-ed l)y means of a gamma ray instrument. As in the case of the emanation, the unit of (piantity is the millicuric. This foil may be used as a uniform source of radiation of short duration. When a radioactive solution is re(|uired for injection into the blood, it may be prepared in the following nuuiner: A small amount of common salt (NaCl) is packed into a small glass bulb. This bulb is heated in a gas flame in older to thoroughly dry the salt, and is then sealed to the emanation apparatus at J7 (see Fig. 2) just as in the preparation of active deposit on the lead foil. After the air is pumped out, the purified I'HKl'AKATIOX OF l{.\nil'M KMANATION 39 eiiiaiuitioii is foi-ccd into tlic sail, by means of iiiert'ury raised to llie small hull). In 3 or 4 hours, when the nuixinnnn amount of active deposit has formed and eolleeted on the salt <>rains, the mereury is h)Avered ai>ain. The emanation is alloued to pass into another part of the ai)pai'atus to he collected in the usual way. The bulb is then cut off and distilled water is forced in Mith a hypodermic syrin,<>e in sutfu'ient amount to make ai)proximately a normal i)hysiolo<>ieal .salt solution. The "active" Avater is subseciuently withdrawn in Ihe syringe. As in the former case, the amount of active deposit in the syringe is determined by the gamma-i'ay instrument. The activity of the syringe is usually determined before and after the injection of the solution, in order to estimate the exact quantity of active deposit administered. The quantity administered will be the ditference in these 2 values. Proper allowanee for the decay of the active deposit must be made. CHAPTER V THE RADIATIONS FRO:\I RADIUM AND ITS DECAY PRODUCTS Rutherford states that from a theoretical staiuliioint it is desirable to restrict tlie term ''radioactive" to substances that undero-o spontaneous atomic transformation. From this point of view, a few substances may be said to be radioactive M'hich apparently emit no radiations at all but M-liicii do transform themselves spontaneously and give rise to new sub- stances. From our present standpoint, however, we may fairly define a radioactive substance as one that, while undergoing atomic transfor- mation, spontaneously and continuously emits peculiar rays. These rays are invisible but are known to be present because of certain phenomena which they cause. Among the interesting properties possessed by these radioactive rays ai"e their power to ionize a gas, to affect a photographic plate similarly to the actinic rays of sun light, to cause certain sub- stances to fluoresce in the dark, and, most important of all, from our present standpoint, to cause the modification or destruction of vital tis- sues exposed to their influence. While radium itself emits the easily absorbed alpha rays, its decay products, Ra B and Ra C emit the more penetrating beta and gamma rays. The beta and gamma rays from Ra B are less penetrating than those from Ra C. Confined in a tube for therapeutic use, the only real function of radium or its next decay product, radium emanation, is to produce Radium A, B, and C as fast as the latter products disintegrate. ALPHA, BETA, AND GAMMA RAYS There are tlii'ee different kinds of i-adiations emitted by the radio- active substances. These are known as alpha, 1)ela. and gamma rays. The table jirevionsly given fsee list of radioactive substances) will suffice to nuike clear the ])articular ray that each of the products emits. It will be hel])ful to describe at this point the pro])erties of the different kinds of rays. Alpha Rays Alpha rays are material paiMicles having a donble ])ositi\H' charge and a mass four times that of the hydrogen atom. In fact, tiiey are merely ])ositively charged helium atoms shot out from the radium atom, as it transnintes. wilh an initial \-elocity of 9,000 to 12,000 miles per second. They have a very great ionizing power, but are readily absorbed, the thinnest layer of metal or a sheet of note paper being sufficient to stop them. The "range" or greatest distance that an alpha particle from any 40 RAHIATIOXS KKO.M KAHIIM A\l> ITS I)i:CAV PHOHrCTS 41 of llic I'adioacI ivc siil)st aiiccs can tra\('I in ail'. (li'piMids ui)nn its initial velocity aiul Iho toinixTaliire and in'ossuro of tln' air. Vnv an al]ilia particlo of radium in aii- at standard coiidilidiis of li'inpcralurc and pi-(>ssiir('. tlio raiio-e is ;i.M cm. in other words, the alpha rays of radium ai'e completely absorbed or sto])i)ed by 3.3 cm. of air ami beyond this distance their characteristic eff'ects cannot be delected. A]|)ha rays ai'c analoiious to the canal rays of a ('rook(>s tube, and like them may be deflected sli<>litly by a veiy powerful ma<>:netic field. While usually re- ferred to as alpha I'ays. the tei-m ali)ha particle is perhaps preferable. A .u'rain of radium in e(|uilibrium with its decay products, Ra Emana- tion, Ra A, B. ami ('. emits enei-iiy w itli its rays at the rate of 136 calories per houi". Of this eneruy 125 cabu'ies are borne by the alpha rays, 4.5 calories by the beta rays and (i.5 calories by the oamma rays. Beta Rays Beta I'ays ai'C swiflly moxinu', neu'atively chai'ii'cd idectrons and are identical in type with the negatively charged particles constituting the cathode rays of the C^rookes tube. They are about ''is4o the mass of the hydrojren atom. Soft, medium and hard beta ])articles may be dls- tin<:uished accordin<>' to their velocity and power of ])enetration. The slowest beta particles are comparable to alpha rays in penetratinfj' power and are known as soft beta rays. The swiftest beta particles have about the \elocity of liiilit and luive one hundred times the penetrating: power of alpha rays. These are known as hard beta rays. The velocity of the hard beta rays from Ka (' is 9(i per cent of the velocity of light and it is estimated that to give an electron this initial velocity requires a difference of potential of 2.0()().()00 volts (approximately a 16 foot spark in air). BetAveen the softest and hardest beta rays there is a series of so-called medium beta rays, which are ijitermediate in their power of penetration. The beta rays dei-ived from Radium B aiul Radium C are one half absorbed after passing through 55 cm. of air at atmospheric pressure and room temperature. The beta rays from Radium C are half absorbed by 170 cm. of air. Beta rays may also be deviated in a mag- netic field but in an opj^osite direction to the deviation of the alpha rays because the l)e1a I'ay is the negative electron, lieta rays are also de- flected much more than alpha rays because their nuiss is very much less than that of the hitlei'. .\s we have previously mentioned in the case of the ''alpha rays." the term "beta particle" is pi'eferablc. In defer- eiu'c to custom. liowe\"er. the term "beta i'a>'" is retained. Gamma Rays These are undulations of the ether, or electro-magnetic waves, and are similar to x-rays, excejit that their wave length is much shorter than that of the latter. The velocity of the gamma rays is the same as that of lioht. 42 RADIUM THERAPY The production of gaiiinui rays is due to the veiy intense cleetronie vibra- tions whicli are set n\^ in the structure of a radio atom from which a high speed beta ray is escaping. The forced vibrations of the electrons give rise to very high frequency or short wave length electro-magnetic waves or gamma rays. Thus it is seen that the gamma ray is a secondary phenomenon, and the energy of the gamma rays represents energy lost by the beta ray as it escapes from the atom which gives it origin. The absorption of gamma rays is an electronic property of matter, as contrasted with atomic or molecular absorption of longer wave lengths such as ultra violet and visible light. When the gamma ray pulse encounters an elec- tron in matter which can vibrate in harmony, energy is transferred to the electron and it thereby takes up a high velocity and becomes a "secondary beta ray." This phenomenon of energy transfer from a wave to a ])artiele lias a very good analogy which is familiar to most of us in the sound vibrations Avhich the striking of a certain note on an instru- ment will set up in a loose bit of woodwork, etc., in a music room. Here the energy borne on air waves is transferred to the particle which can vibrate in harmony Avith the rate of the air waves. In the case of gamma rays, so few electrons are encountered that can vibrate in harmony, that the gamma ray pulse must pass through enormous numbers of electrons, (i.e., great masses of matter) before it loses much energy. This interpre- tation explains the "hardness" or penetration of the gamma rays. In the case of x-rays, which have a much lower rate of viliration, more elec- trons are encountered that can vibrate in harmony; therefore the x-ray pulse loses its energy more easily, or, as we say, is more easily absorbed in matter. The terms soft, medium and hard gamma rays are used to indicate dififer- ent degrees of penetrating power, just as in the case of the beta rays. In general, gamma rays are from ten to one hundred times more penetrating tlian beta rays, and consequently have a smaller ionizing power. Tlie gamma rays are half absorbed after passing through one hundred and fifteen meters of air. Like the x-rays, the gamma rays cannot be deflected bv a magnet. CHAPTI'lR VT ABSORPTION AND FILTI^ATION OF KAYS AVe have already referred to the fact that the radiations are capal)le of penetrating: opaque matter in varying degrees, certain types of rays being easily absorbed wliile otlier types are stopped witli the greatest difficulty. In this chapter ^\e shall consider some of the ])ractical ad- vantages of filtci'iuji' or absorliiiip- certain ty])cs of rays by means of screens. ABSORPTION OF RAYS Alpha Rays It lias already been stated that the alpha I'ays from radium are very easily alisorbed. The glass wall of the emanation tube, a sheet of note paper, the film of a soaj) bnbble oi" a layer of moisture on the skin is sufficient to stop them. Beta Rays Hard beta rays according to Rutherford may be half absorbed by 0.1 mm. and may be completely absorbed l)y 2 mm. of lead. The absorption of the beta rays by various kinds of matter follows closely an exponential law. For example, if one half of a given quantity of beta rays of a certain type is absorbed by 0.2 cm. of aluminum, ""/i of the original amount of rays will be unal)sorbc(l after ])assing through 0.4 cm. of aluminum, Ys of the original amount will be unabsorbed after passing through 0.0 em., and so on until comjilete absorption. As we have stated before, the beta rays are heterogenous aiul have different penetrating powers. The relative absorption of beta rays depends therefore upon the type of rays that is chosen for experiment. The hardest or most penetrating beta rays are absorbed to the extent of !)3.8 per cent by 1 cm. of epithelial tissue. Their intensity after passing thi'ough 1 cm. of epithelial tissue, is, therefore, only fi.2 per cent of that exhibited at the surface of the skin. This estimation docs not take into account the diminution of in- tensity due to divergence of the i-ays with distance from the s(uirce. The intensity of the beta radiations from i-adium (' is I'cduced to i.j the initial intensity after passing through 17 meters of air. at ordinary I'oom temperature and atmos|iheric pressure. Gamma Rays The hard gamma i-ays from radium C are half absorbed by 14 mm. of lead. Just as in the case of the beta rays, the gamma rays from radium 4;'. 44 RADIUM THERAPY are absorbed approximately in aecordance witli an exponential law. This bnv is followed, however, only in the event of the rays bein^ allowed to pass first throngh a few millimeters of lead, the softer gamma rays being thus absorbed. According to the measurements of Giraud, which have been mentioned previously 20.4 em. of water will absorb |4 of the gamma rays from radium. For theoretical purposes, water may be considered as the equivalent of soft tissues in absorbing power. Gudzent states that 4 per cent of the successively remaining gamma rays are absorbed by each centimeter of tissue traversed. According to Rutherford 26.5 cm. of soft tissue would be required for the half absorption of the hardest gamma rays from radium. These estimations may be compared with the penetrating power of x-rays which are half absorbed, according to Colwell and Russ, by 4.9 cm. of soft tissues. As to the diminution of their intensity with dis- tance, hard gamma rays are reduced to one half their initial intensity after passing through 115 meters of air at ordinary conditions of room temperature and atmospheric pressure. Secondary Radiations All three types of rays — alpha, beta and gamma — produce secondary radiations when they impinge upon matter. We may l)riefly consider the secondary radiations produced by each of the three types of rays. (a) The secondary rays produced by the alpha rays are slow beta particles and are sometimes called "delta rays." The secondary rays due to alpha rays are naturally without practical importance from the therapeutic standpoint, (b) Just as the cathode rays, striking the target of the x-ray tube, set up x-rays, so the primary beta rays from radium when they strike matter set up a type of gamma radiation. The intensity and penetrating power of these secondary gamma rays increase greatly as the atomic weight of the substance impinged upon increases, since these gamma rays cor-respond to the characteristic x-rays for the par- ticular element, and the higher the atomic weight of the element, the moi-e penetrating are the characteristic x-rays. The quantity of secondary gamma rays that are produced depends upon the amount of beta radia- tion that is absorbed aiul the thickness of the material that is radiated. (c) AVhiMi llic ])rimarv gannna rays from radium strike matter, a part of the original beam is scaltcriNl in all directions altlioiigli the (piality of the beam is not altered. Jnst as in the case of the primary beta rays second- ary radiations ai'c also set up by the primary gamma rays. These con- sist of secondary gannna rays and secoiulary rays of llie Ix'ta ray type. Our knowledge of the secondary gamma rays is very imperfect. The secoiulary beta rays have a penetrating power 1lia1 is nearly equivalent to that of the in'iiiiary Ijcta rays. When heavy elements such as lead ABSORPTTOX AXD FILTRATION OF RAYS 45 are impinoed upon hy uamiiia rays the secondary beta radiation is some- wliat more penetratiiii-' than wlion li*ih1or olomonts such as brass or aluminum are radiated. FILTRATION OF RAYS The principle of filtration and the use of screens in the treatment of diseased tissue may be referred to at this point. Wickham, Deg-rais and Dominici were ai)parently the first to use and advocate the employment of rays obtained by filtration. By interposing between the radioactive substance and the ti.s.sue to be treated, various metallic and nonraetallic materials, the less penetratino' rays may be absorbed, i.e., removed by filtration. Substances used for absorbing radiations are known as screens or filters. In the treatment, for example, of a tumor below the surface of the skin, we may absorli by means of screens the undesirable types of rays before they reach the skin, allowing oidy the more penetrating rays to pass through the screen and atfect the tissues. The skin, being thus relieved of the absorption of the less penetrating rays, will receive a minimum amount of injury, while the deeper layers of tissue under proper conditions, may receive nearly as much radiation as the superficial layers. If we wish to absorl) the alpha rays we may theoretically place l)etween the radium and the skin a screen of ^^i,,,, millimeter of aluminum or a sheet of writing paper. Tn reality, however, the alpha rays do not pene- trate the walls of the glass tube or other apparatus in which the radium is confined. If we wish to intercept most of the beta rays we may interpose between the radium and the tissues a screen of 1 millimeter of lead. This filters out more than 99 per cent of the l)eta rays. One may thus use nearly pure gamma rays, M-hich will not be absorbed but will pass through the screen. AYhen massive doses of deeply penetrating rays are used, it is desirable to al)sorb in addition part of the softer gamma rays. Brass screens 2 mm. thick may then be used. It is quite evident that a whole series of metallic screens of different thicknesses and densities may be used in order to al)s()rb oi- filter out varying portions of the beta and gamma rays and that the results of treatment will vary accordingly. Screens The screens used for all types of therapeutic a])pli('ators may be de- scribed here. Screens are ordinarily made of silver, gold, platinum, brass, lead or alumiinim. For external applications, brass or silver screens answer almost every juirpose. It is believed Ihat the secondary radiations from brass are not so irritating as those from denser metals. It is best to use rather simple and uniform screening until familiarity is obtained with Ihc clTccts of radium on llu' tissues. 46 RADII TM THERAPY AVhon ti'oatiiig the iiiterioi- of the various natural cavities of the body, sueh as the uterus, esophagus, etc., gold or platinum screens have a cer- tain advantage as their great density permits the use of a much thinner screen than if brass or silver were used. In such case the desirable effect of di.stance in reducing the intensity of the rays is sacrificed. This may be compensated at times by the use of thicker nonmetallic cover- ings such as rubber of 2 or o mm. thickness. While theoretically screens of almost any material or thickness may be employed, it is often advisable in actual practice to employ a few different thicknesses of the same metal in order to simplify the technic. Silver screens having a thickness of 0.1 mm., 0.5 mm., 1 mm., and 2 mm. are probably the most generally useful in the routine application of radium. Screens of these thicknesses will absorb approximately 50 per cent, 96 per cent, 99 per cent, and 100 per cent of the beta rays. The skilled technician may use a greater variety of screens. In addition to those already mentioned the follow- ing screens are useful. Lead Mo, Yw, 1, and 2 mm. thick. Platinum Vio and Y^q mm. thick. Aluminum Moo, Moo, Mo mm- thick. Brass Mo, 1, 2, 2.5 mm. thick. For practical purposes it is sufficiently accurate to say that the ab- sorbing power of a metal for a given type of beta or gamma ray in- creases in proportion to its density. Table VIII Avill suffice to indicate the relative density and consequent ray-absorbing power of various materials, some of which are used as screens. From a consideration of this tal)le it is an easy matter to calculate the thickness of different materials which would be required to absorb Table VIII RAY ABSOKBING DENSITY THICKNESS REQUIRED THICKNESS REQUIRED TO SUBSTANCE: (APPROXIMATE) TO ABSORB 50% OF ABSORB 99.9% OF THE THE HARD BETA RAYS HARD BETA RAYS Gum rubber 1.0 1.00 mm. 8.50 mm. Water 1.0 LOO " 8.50 " Soft tissues 1.0 1.00 " 8.50 " Bone 1.7-2.0' 0.00 " 5.00 " Common glass 2.0 0.40 " 3.30 " Alumiiiiiiu 2.7 0.40 " 3.20 " Steel 7.7 0.14 " 1.15 " Brass 8.5 0.13 " 1.10 " Nickel . 8.7 0.13 " 1.10 " Silver 10.(5 0.10 " 0.80 " Lead 11.3 0.10 " 0.80 " V,(M 19.3 0.06 ' 0.50 " Platinum 21.5 0.05 " 0.40 " ABSORPTION' AXn FILTHATIOX OF KAYS 47 a oivon amount of tlie hard beta rays. Let us suppose, e.g., that Ave wisli to use a series of brass screens Avhieh Avould equal ^/],, mm., -^lo nim., 1 mm., and 2 mm., of silver. A simple calculation of the relative density of tlie metals sIioavs lliat brass screens e((uivaleut to silver screens of 1 n p the alcove thicknesses, must be- ^ of ^/o mm., y^o mm., 1 mm., and 2 mm.: i.e., a]ipro.\imately ^s mm., % mm., 1.25 mm., and 2.5 mm. thick. Similar calculations may be made for other materials in the table. It has been found that different thicknesses of silver will absorb the proportions of the hard beta rays indicated in Table IX. Table IX THICKXESS OF PER CENT OF HARD PER CENT OF HARD SILVER SCREEN BETA RAYS ! ABSORBED BETA RAYS LEFT 0.1 mm 50. 50. « 0.2 0.3 0.4 0.5 O.G 0.7 0.8 0.9 1.0 75. 87.50 93.75 96.88 98.44 00.22 99.(31 99.81 99.91 25. 12.50 6.25 3.12 1.56 0.78 0.39 0.19 0.09 Upon examining the table it may be seen that the percentage of absoi'ption by a given thickness of the metal follows an exponential law; i.e., if 50 per cent of the hard beta rays remain nuabsorbed after passing through 0.1 mm. of silver, Y^ of the original amount will remain unabsorbcd after passing through 0.2 mm., i/{, of the original amount will remain unabsorbed after passing through 0.13 mm., and so on until its complete absorption. Depending upon the apparatus with which they are to be used and the lesions that are to be treated, screens of diiTerent shapes and sizes may be required. For tlu' glazed i)la(iues. pieces of metal of the material and thickness desired may l)e cut to fit the face of the apparatus. The metal screens may be round or square or of any other shape desired. Wliile they may ])e nuide extemporaneously, it is much more convenient to use screens that have been previously fitted to suit each apparatus. For the tubes containing radium or radium emanation, a set of cylin- drical metal screens of different patterns is also essential. It is con- venient to have certain screens made in such a way that part of the wall is cut out to form a window ("window screen"). One may thus treat a certain part of a lesion opposite the window with a greater volume of rays than the other parts. 48 RADIUM THERAPY Secondary Radiations In the practical use of screens or filters we meet with difficulties on account of the secondary radiations (Rays of Sag'nae) that are formed in these screens. As these secondary radiations are less penetrating- than the primary radiations that produce them they always tend to defeat the object of the screen. While the secondary radiations may not seriously affect the skin surface, it is customary, as we have said before, to inter- pose between the metallic screen and tlie skin, one or more millimeters of nonmetallic substance, such as gauze, rubber, filter paper, or wood, in order to absorb them. Filter paper is excellent and, being composed of pure cellulose of low density, does not appreciably absorb the gamma rays. Cork or soft wood is commonly used by the writer because of its greater convenience. According to Hayward Pinch, a layer of aluminum 0.2 mm, in thickness completely absorbs these secondary "rays of Sagnac." CHAPTER VII THE ABSORPTION OF riA]\r.ArA RAYS IX WATER 111 lliis cliaptei' w(> sliall yivo tlie rosulls of some of our cxperiinental Avork on the ahsoi'|)1ion of uainina i"ays. In these experiments, wliieli wei-e undertaken primarily to determine, if ])ossil)le, tlie absori)tioii of ti'amma ra\'s m tissues, it Avas, of eonrse, impossiI)le to phu-e tlic ioiii/atiou chanibei' used in determiuinj>- the in- tensity of the radiations beneath the skin itself. Water was therefore used in our ex])erinu'nts as beiny the most suit- able medium, inasmuch as i1 is similai" in absoi-bing- properties to the tissues. This medium was jireviously eui|)loye(l by Kroenig and Friedrieli for determiinng the absorption of x-rays. The nuiin ])rol)lem that "\ve undertook to solve was whether the scat- tering of Ihe gamma i-ays causes any change in the intensity of the rays at various depths below the surface of the skin ami if so what the change is. So far as 1lie ])liysical side of the ]n-oblem of al)soi'])tion ami scattering of radiations is concerned, almost all the ])re\ious work mentioned in the literature lias been done by simply intei'posing thin sheets of absorb- ing material between the source of radiation and the electroscope. In some eases an ionization i-hamber was used. Of such nature, for example, was the work of Hewlett, Avho discusses the mass absorption and mass scattering coefficients of radiations of wave length .18 to 1.05 A° in various substances including water. He found th(» mass absorption co- efficient by finding the ratio of the filtered to the untiltered beam. The results indicated excess scattering for the shorter wave lengths. KoN'arik treats of the effect of dilTei'ent lyjx's of ionizalion chambers. He used an ami)Iitication of the current with a three electrode tube. riii-isten treats the ])roblem of measuring "intensity" and "dose" fi'om a theoretic standpoint. Kroenig says that the cai)acity can be made low by using a vvvy fine center electrode, but if this is doiu', the satura- tion voltage is high. Kroenig and Friedri(di. in Iheir wor]\ " Physikalische uiid Biologische Oruiidlageii der St rahleii-l herapie," (h'al extensively wilh x-i'ay measure- ments of this nature. AVe may, therefore, give some of the details of their experiments, in his experiments with x-rays Friedrich used an appai-atus of ])i'act ically the same foi-iii as the fii-st 1y])e of cliandter which we emph)ye(l ; the only difference consisted in the fact that in his ajipa- ratus the coiniecting tubes were much larger ami wei'c insulated with rubber. The nii'thiid thai he employed has the great adxantage of Ix'ing llexible 49 50 RADirM THERAPY but the insulation probably could not have been as satisfactory as in our apparatus. The size of the cable gives it a smaller capacity, but may render the scattering different. Friedrich used a Wulf string electrometer, which has a very small capacity but is very insensitive. In fact, he found it impossible even to calibrate his apparatus with seventy milligrams of radium, because the other errors due to leaks were so large. He was forced to use a gram of radium and even under these circumstances did not take data under water. For almost all of his measurements of gamma rays Friedrich used only an electroscope, not an ionization chamber. His apparatus was placed on a wooden table in the middle of a room in order to avoid "scattering." Friedrich also had trouble with polarization of the dielectric; i.e., IC @E/ B * ^-»timAH*u*t^b. B' - E Fig. 4. — DiaKraiii showing electrical cniinectioiis for null nietlind of using ionization chamber. El, electrometer or electroscoiie: R, rheostat; IC. ionization clianiher; E, earth; C, condenser; B, B', batteries. charges crept out of it as one first used it ; tliis had also l)een observed with our own apparatus which we shall describe below. Friedrich constructed an ionization chamber of aluminum having found that this material was the one of the lowest atomic weight that was best suited for his purpose. He also constructed a chamber made of horn coated with graphite. He us(>(l carbou for the electrodes. Friedrich calibrated his aluminum cliamber with llic horn chaml)er for comparison of different hardnesses of x-rays. ^FakoAver and (Jeiger ("Practical ]\[easuremeuts in Kadioactivity") give a null metjiod of using an ionization cliambei-. This method consists ill bjihmciiig the curi-eiil to be measured (in llic i(uiiza1iou cliamber) witli Uie charge induced oii a condenser, ai'rauged in the maniu^r shown, l)y varying the voltage api)lied to the other ])late of the latter. (Fig. 4.) The principle of the ai)paratus consists in keeping the gold leaf A15S()lv'l"n(»\ OF (!AM.\1A IfWS I\ WATKK 51 or niiiTor ;is iksii'I.x' slat 'kukii'v as jxissililc I)y iiidviii^' tin' xaciahlc (*f)n- tact on tlic rheostat, and in incasnring' tlic tinu' necessary for a ;") cm. hi. A Avooden support for the radium applicatoi-. that was callable of mo\('ment, was constructed so that the shelf for Iioldini;' the radium to 52 RADIT^M THERAPY be Tised cduld cillici- ])v br()iit>]it down to touch the ionization chamber or could he raised to a heijrht of 25 em. above it. The shelf could also l)e moved 25 cm. to the side iu either direction. "We thus obtained for the shelf a fi-eedom of vertical motion ainountinti to 25 cm.; of sidewise motion 50 cm. in two directions. Later a string was found sufficient for changing' the jiosition of the radium and was therefore used to sus- pend the a])])ai'atus at dift'cicnt heights. The level of tlic water and also the heiiiht of tin* radium applicator above the surface of the Avater could thus be varied. The ionization chamber itself was fixed. The ionization chand)er was first tested. A wire al)out four meters long covered with cotton in^idation I'an from tlie inner electrode, (con- necting Avith the wire passing through the guard tube) to an ordinary gold leaf electroscope. With this arrangement the speed of leak M'as found to be extremely large and also variable. One seventh of a milli- irram of radium was sufficient to .produce a considerable change in the W.£ s T.C. ^ ^ w ^ 1 f8 ?£ Fiji. (t. — Diagram of a|)paratus used for measuring absorption of Kamma ray.s in water. W.F... Wilson tilted electroscope; H. ground; B, source of luRh potential; .Sk'. Sxv' , switches; W, water; l.W. level of water; RA. railium applicator; .S', adjustal)le support; /.C, ionization chamber. leak, but, of c(»urse, the actual ciin-eiit in the chamber itself was entirely too small to be measured. The use of suljihur sujiports which were encased in glass for the wire, did n(»t materially lessen the size and variability of the leak. The wii'e was therefore encased in aluiiiinum tubing filled with sulphur. The first microsco])e used A\as of low nuignifieation; hence the read- ings correspond to a large change in voltage. It was found that the electroscope could be placed much closer to the radium than had been expected Avithout introducing a leak due to the ioiiizatif.n in the electroscdpe comparable with the other leaks in the a|)|)aiatus. A switch was introduced to .separate the ionization chamber and the tube from the remaining jiarts of the conductor. The switch that we used consisted (»f a very small glass cup inbedded in siil|)hiir and filled with inei-ciiry. into which the wires dipped. AI5S()1{I'TI(>X OF (iAMMA KAYS I \ WATKR 53 First Observations of Intensities With First Type of Ionization Chamber Readings were taken with a very liiiili |)()tential on the leaf. The speeds of fall with the switch closed compared to those with the switch open varied almost inversely as the capacities of the two systems, thus showing- that the r'cading was almost all leak and that there was little if any true current. Reading's were extremely ii-regular. It made a great difference hoAv high the leaf was charged to start with; the leaf had to be kept charged for some time before taking readings; nu)vements of the air affected results, etc. The leak was minimized by using various devices until finally it was of the order of five minutes under very favorable conditions. Complete confidence could not be placed in the results of the readings, hoAvever. A voltage of about 430 volts, of which the scale corresponded to 25 or 30, was then used. The natural leak with radium present was still greater than the effect to be measured. To get rid of this leak, an entirely different ionization chamber (Fig. 7) that could be used with a AVilsou tilted electroscope was finally de- Fig. 7. — Diagram of st-cond type of ionization cliainl)er. .S', snlpluir; .//,, alununnm; .1, ani1)er. vised. The inner chaml)er was made with approximately the same ex- ternal dinuuisions as the previous chamber but heavy alumiiuim 3 mm. thick was used in its construction. The whole space between the inner and outer cylinders was filled with sulphur, except for the end at which the innermost electrode entered; this end was fitted with an amber washer. The guard tubes extending from each end were filled with sul- phur as in the first type of chamber. The advantages of this second type of clunnber are evident. Tn the first place, the walls of the interior chamber can be charged to a high potential and the rise of the potential of the inner electrode from the ground potential up can be obtained. Under these circumstances, the only leak that can jxtssibly occur in this part of the apparatus is from the inner electrode and the connecting Avires to the ground. There can be no leak over the sulphur from high potential to the inner electrode be- cause that is prevented by the guard ring. The current that nuiy floAV from high potential to the ground does not affect the electroscope. The only other leak possible is in the electroscope itself from the high poten- tial to the leaf. The high |)otential difference is thus ett'ective in producing the desii-ed curi-cnt, but only tlie low difference is etfective in producing leaks. This second tyi)e of elunnber is also part icuhirly suited for work with 54 RADIUM THERAPY the Wilson lilted clci'troseope. since the hitter measures tlie rise in potential al)ove that of the ground. The Wilson type of electroscope has the advantage of great .sensitiveness ; indeed the sensitiveness is very great if the electroscope is proi)erly adjusted. Instead of tlie thirty or forty volt change in potential nsed with the ordinary electroscope, a voltage change of three or foui- volts or less can be used. Furthermore it has a low capacity; and the volume of gas contained is small. Second Series of Observations with First Type of Ionization Chamber An attem})! was now made with the old cliaml)er to apply the method wliieh wi' pro{)osed to use witfi the new chamber; i.e., the outer case l-'ig. ti.— IiiU-iisity ill \v:itir. I'.asc ut applicator 3 cm. aliovc surface. ABSORPTION OF (i.V.MMA KAVS I X WATKK 55 of the chamber Avas kept at liigh potential and the rise of the potential of the inner electrodes and leaf was noted. Unfortunately the results were not entirely trustworthy. The difficulty with the application lay in the fact that the guard tube for a distance of about twenty centi- meters was necessarily at high potential, giving- considerable opportunity for leaks across the end. HoAvever, the following results are at least qualitative as they indicate the manner in Avhich the field in air, and at different distances below the surface of the water, varies. Fig. 8 indicates that the intensity below the surface of the water no- where approaches that at the surface, but decreases quite rapidly as one goes down. This is obviously to be expected, merely from the opera- Fig. 9. — Intensity below surface cf water. Base of applicator cm. above water. 56 RADIUM THERAPY tion of the inverse square law alone. The curve is taken with the base of the applicator directly over the spot at which the field Avas measured, and at a constant distance of three centimeters from the surface of the water. It sives the intensity at various depths below the surface of the water. Fig-. 9 indicates tliat similar results were obtained when the base of the applicator was six centimeters' above the surface of the water. The inten- sity at the surface Avas of course less to start with, and the decrease was more i>radual due to the action of the inverse square law. This is evident from the fact that with a point source the intensity changes I'lR. lu. — 1mc1<1 .1 cm l)il')w surtact of water. IJase' of a|>plicator 1 cm. above water. AHSORI'TIOX OF GA>n[A RAYS IX WATKK 57 fourfold in going from five to ten centimeters; one must go. however, a distance of twenty centimeters before the intensity changes again fourfold; i.e., a movement of five centimeters in the first and ten centi- meters in the second case is necessary. Furthermore the actual change hiot the ratio) is much less in the latter case. The next series of curves shows the change in the field at a given dis- tance below the surface of the water as we go laterally from a point directly below the center of the radium applicator. The first of these curves (Fig. 10) shows the field at a depth of five centimeters. The decrease here, as one soes out from the axis is rather abrupt, as we "^m ^ ^ $ ^ ^z n SeS &Bd rmiD tccffi ^2 Bzcra ^£ ^3 S 2^ Fig. 11. — FieKl 10 cm. below surface of water. Base of ai-plicator 1 cm. from water. 58 RADIL'M THERAPY should expect, sinee 13^' + 5- = 194, 13- + 10^ = 269, i.e., a factor of 1.39 is present from the operation of the inverse square law in the change from five to ten centimeters. Fig. 11 shows the field at a depth of 10 cm. The decrease is more gradual. 18- + 5- = 349, 18- ^ lU-= 424. The ratio between these two numbers gives a factor of 1.22. (These factors are not actually the numbers by Avliich tlie intensities at 5 cm. and 10 cm. distance from the axis should differ, since the radium was not at a point, and there is absorption and scattering). Fig. 12 shows the field at a depth of 15 cm. The decrease is here more I'lR. \2. — Field 15 cm. Iiclow surface of water, liasc of applicator 1 cm. from water. ABSORPTION OF GAMMA HAYS IX WATKK 59 gTadual still. We find that 23- + 5- = 554, 23- 4- 10- = 629. The ratio between tliese two numbers gives a factor of 1.13. The distance changes relatively (and also actually) less as we go out, perpendicularly to the axis, than when the distance along the axis is small. Fig. 13 represents the field on the surface. The difference between this curve and the curve in Fig. 12 is extremely marked. The factor here would be 1.84. (8- + 5= == 89, 8- + 10- = 164.) The foregoing series of curves (Figs. 10 to 13) was taken with the base of the radium applicator 1 cm. from the surface of the water; i.e., the radium tubes were a little over 8 cm. from the surface of the water. ll¥l rrti^ ;?r rtoZ5 t^(f;t -xr} mr iUt n?- iSE: a ^m Ititi mi ■iVm. Fig. 13. — Intensity on surface of water. Base of apiilicator 1 cm. from water. CO RADIl'M THEUAFY The curve in Fig. 14 is taken under the same conditions as the pre- vious curve, but is plotted to a different scale horizontally and vertically from the other curves. The distances are taken diagonally from the axis of tlu^ ai)plicator. l-iK. 1-1.- liilciihilN (Hi Miifaci- of water. Jiase of apiilicator 1 cm. from water First Observations of Intensities with the Second Type of Ionization Chambers We iiKiy now discuss the scries of cui'vcs liikcii wi1li the second type of ionization chainher. One of these curves \v;is taken as a calibration curve for tlie chanibei'. The leak across from the inner electrode to ABSORl'TIOX OF GA:srMA KAYS IX WATKR 61 the jiTouiul Avas not siiuiU ciiou^li lo make conditions t'a\-oral)U' ; it chano-ed markedly the values obtained from the reciprocals of the times. A theoretic deduction of the correction to be ajoplied is as follows: Let c be the current due to the ionization chamber, i.e., that which is to Fig. 15. — l-'ifld in air. /, ii;iralit.l to plane of tul'es at .i..S cm. distance. //, iierpcndiculaf to pUi of tiilK'S, along axis. be measured: rT that due to tlie leak from the inner electrode to the ground; V being the voltage to which the leaf has become charged; e" (V'-V) that from high potential to leaf. V being the high potential. Then, neglecting a constant capacity factor, 62 RADIUM THERAPY dV =c-c'V+c"(V'-V) at dV dt =z{c+c"V')-{c'^c")V .17 dV /v ay ^f o {c+c"F')-{c'W)V ^J o '^^ (c+c"r')-(c'+c")F log = -{c'W)t C-rc" V c+c"l''-(c'+c")r—{c+c"r')e-^''''''"^* (c'+c") V c+c"f''= l_e -(c'+c")t -c"V' !■( riicndi lilaiu- <.f \\ ABSORPTION OF GAMMA RAYS IX WATER 63 Table X Intensities at Various DISTA^•cEs along the Line Perpendicular to the Center OF A 6x6 CM. Plaque, with 9 Tubes Containing 100 mc. in all distances intensities (theoretic values) in cm. at different points on the axis 8^5 L29 " 9.5 1.05 10.5 .866 11.5 ,727 12.5 .619 13.5 .533 14.5 .464 15.5 .407 16.5 .360 17.5 .321 18.5 .288 19.5 .259 20.5 ,235 21.5 ,214 Table XI Intensities at A^'apjous Distances from the Line Perpendicular to the Center OF A 6x6 CM. Plaque, with 9 Tubes Containing 100 mc. in all All Values Are Taken at a Distance of 8.5 cm. from the Plane of the Tubes experimental values (corrected by calibration curve) 1.28 1.28 1.21 1.10 1.04 .93 .85 .77 .67 .63 .56 .50 .46 .43 .40 .35 .32 The other curves were tlien corrected by means of tlie calibration curve and for air -were found to ao'ree very M'ell with the tlieoretic values. In Fig. 15, Curves I and II were taken in air. They show the funda- mental characteristics of such curves. Curve I is taken at a constant dis- tance from the plane of the tubes and at different distances from the axis. It shows zero slope to start with, pradually increasino- o-radation, tlien a point of inflection, and a e/^ plapi or^utes il :<': '^ Oafanzeh&nn-^vr-fa^^'oflt/ater inccti V\v.. I/. V ctilati- Ki'l m u.ii.r. 1.(11. iiiilii-iil.-ir to plaiu- ..f tiihis. o, ICxiicriniLiital valuts; .i", values cal I (in the basis of no rilisorption; A. values calculated on the basis of ;ii = .033. ABSORPTION OF GAMMA RAYS l.V WATER 65 ill air was almost identical with that obtained previously; it is practieally linear, / == 140 +.253 fitting the calibration curve with a maximum error t of a few per cent. Data were taken later for depths down to ten centimeters. The applicator used was 10 cm. square and 10.7 cm. high. The base of the applicator w^as kept at a distance of 3 cm. from the surface of the water, and hence the plane of the tubes in every case was 14 cm. above the surface of the water. The first column in Table XII gives the distance of the point at which the intensity was measured from the plane of the tubes ; the second its dis- tance below the surface of the water. The third column gives the observed valvTe of the intensity. The fourth, the value calculated without allowing for any absorption by the water, i.e., the value which it would have had if there had been no water present. The fifth column is the per cent differ- ence betw'een the value observed and the value calculated on the basis of no absorption. The sixth and eighth columns assume absorption coefficients of .033 and .05 for the water respectively, while the seventh and ninth columns give the percentage differences between the values calculated on these assumptions and the values observed. Table XII DIS- DIS- OB- CALCULATED CALCULATED TANCE TANCE SERV- VALUES. FROM BELOW SUR- ED VAL- PLANE AIR. % DIF- /i=.033 % DIFF. fj.— .05. % DIFF. OF FACE UES. NO AB- FERENCE OBS 'D. obs'd. TUBES. OF SORP- BETWEEN CAL 'CD. CAL 'CD. WATER. TION. OBSERV- ED AND CALCU- LATED. 13.50cm. .05cm. .570 .506 13 .506 13 .506 13 15.55em. 2. cm. .408 .388 5 .363 12 .351 16 16.8ocm. 3.3 cm. .325 .334 _o .299 9 .285 14 18.35cm. 4.8 cm. .257 .284 -10 .242 7 .223 15 20.30cm. 6.75cm. .217 .234 -8 .187 16 .167 30 20.65cm. 7.1 cm. .2]0 .226 -7 .178 18 .158 33 21.75cm. 8.2 em. .198 .204 -3 .155 28 .135 47 23.15em. 9.6 em. .181 .181 .131 38 .112 62 23.95cm. 10.4 cm. .165 .170 -3 .120 38 .101 69 Hence the same general conclusion was reached in the second series of observations as in the first ; viz., that the intensity below the surface of the water was practically the same as though no water w^ere present. This conclusion was now found, however, to remain true dow'n to a depth of ten centimeters. In other words, the increase due to the scattering, under 66 RADIUM THERAPY the conditions nsed, almost exactly neutralizes the decrease due to the absorption. As regards the difference between the observed values and those cal- culated on the basis of /x = .033, the percentage of difference varies from approximately 10 per cent from the shin surface down to a depth of 5 cm. up to 38 per cent at a depth of 10 cm. Using an absorption coefficient of .05, the variation is from about 15 per cent to about 70 per cent. Final Series of Observations with the Second Type of Ionization Chamber Other readings taken with various types of radium applicators and different amounts of radium arranged in various ways appeared to give the same result with the type of chamber used; viz., there was seemingly little change in the gamma ray intensity due to the presence of water. There was possibly a change of about ten per cent in a few readings down to a depth of ten centimeters. Below 10 cm. a slight decrease below the value that would have been obtained in air was noted. Fig. 18 shows tlie relatively insignificant effect of the presence of a layer of water 3 cm. thick as compared with a change of 3 cm. in the distance of the radium from the point at which the intensity was measured. All the curves give the variations in the field as one passes (parallel to the plane of the tubes) laterally from the axis of the applicator. Curve I (Fig. 18) is taken with the base of the applicator 2 cm. above the w^ater and 5 em. from the ionization chamber, i.e., with the ionization chamber 3 cm. deep in the water. The water was then lowered 3 cm. keep- ing the radium in the same place (i.e., base of applicator 5 em. from water and ionization chamber, latter being on surface of water). Curve II (Fig. 18) was then taken. The total effect due to three cm. of w'ater (with no change in distance of radium) betweeii the radium and the object radiated would thus appear to be small. Tlie applicator was then lowered 3 cm. (i.e., base 2 cm. above water and ionization chamber). Curve III Fig. 18 was then taken. This curve shows the rehitively large effect due to this change in distance. Cur\os I and II tlius refer to the same distance of chamber from radium, and differ only in tlie amount of water between the two. Curves I and III, on the contrary, refer to llie same distance of surface of water from radium, and differ only in the deptli at which the chamber was placed. That the difference in the rate of variation of the field depends markedly on the distance of the radium is shown ver}^ well by Curves II and III. Tlie i-ate of change, is, for a point source, as one leaves the axis, inversely proportional to the square of the distance from the radium along the axis, while the relative change varies inversely as the distance. On trying to api)ly the null method mentioned by Makowcr and Oeiger (previously i-cfeiTcd to) it was found that witli the condenser at liand the ABSORPTION OF GAMMA RAYS IN WATER 67 leak over the surface of the insulation (Avhieli was of ebonite) was very great compared to the current to be measured. As a result we gave up for the time being at least, what seemed to be a promising method of get- ting rid of every leak except that in the electroscope. With a proper con- denser the method should be as good as any yet worked out. I'ig. IS.^Diagram showing change in intensity due to distance as compared with change in in- tensity due to absoriJtion in water. Other possible improvements in the technic of the experiments may be mentioned. The electroscope could be evacuated, or shielded with a lead screen. The capacity of the whole system could be decreased by using larger connecting tubes or finer wires; by joining successive wires di- (,5 RADIUM THERAPY rectly and pouring sulphur over the connections the insulation would be improved. The use of thinner tubing- would decrease the weight of alumi- num in the guard tube. One possibility of error must now be mentioned. In case the ioniza- tion chamber allows secondary beta rays from the water to enter in sufficient quantity to modify the readings, the results of the foregoing tests may be misleading, since the effect would be to increase the values in Avater relative to those in air. This does not, however, seem to be probable. The whole series of experiments could be repeated with an ionization chamber made extremely thin in order to intercept and measure the beta rays instead of the gamma rays. The chamber suggested would not be thick enough to scatter the gamma rays appreciably as may happen Avitli the type of chamber that we have been using. Although under these circumstances both beta and gamma rays Avould take effect, the error due to the gamma rays would probably be so small as to be practically negligible. CHAPTER VIII PHYSICAL AND CHEJIICAL EFFECTS OF RADIUM RAYS In this chapter "will be considered briefly some of the physical and chemical effects that the radiations from radium may cause. Most of these effects are due to the action of the alpha and beta rays although they may also result from the gamma rays. 1. IONIZATION OF GASES The rays have the power of discharging electrified bodies such as the electroscope, the rate of discharge depending on the intensity of the radiations. In order to explain this phenomenon the theory has been advanced that the rays produce in the air negatively charged carriers called "ions" which render the air a good conductor of electricity. This property of producing "ions" is known as that of ionization. The alpha rays have a marked ionizing effect ; the beta rays have only one or two per cent of the ionizing effect of alpha rays, while the ionizing effect of the gamma rays is only a few per cent of that of the beta rays. Locally alpha rays have intense ionizing power. Beta and gamma rays have a less intense local action but this is distributed over a larger space. The total ionizing effect of each of the three kinds of rays is probably about the same. The ionizing effect of the gamma rays is probably due to the secondary beta rays Avhich are produced by the absorption or "stop- ping" of the gamma rays. In the chapter on measurement of the beta- gamma ray activity of the radiations this subject has been considered in more detail. 2. PENETRATION OF OPAQUE MATTER The degree of penetration possessed by the radiations may be shown by the electroscope, A radium salt exposed freely in an electroscope causes a very intense ionization of the air and the charged gold leaf moves quickly across the field of the microscope. If the radium prepa- ration is covered with a piece of aluminum foil or merely with a sheet of note paper, the ionization is much less intense and the gold leaf moves much less rapidly. With ten sheets of note paper covering the salt the ionization is about one half as intense as with one sheet. It is evident that the interposition of the note paper cuts off the most readily absorb- able rays which have a marked ionizing effect. By covering the radium salt with various thicknesses of metal, rays of Avidely different pene- trating power may be distinguished. The rays most easily absorbed 69 70 RADIUM THERAPY are known as the alpha rays, those less easily absorbed are the beta rays, while those least easily absorbed are known as the gamma rays. Alpha rays are absorbed hy about .089 mm. of epithelial tissne. They are therefore of little or no therapeutic importance. The most pene- trating heta rays are half absorbed by 0.1 mm. of lead and to the extent of 99.9 per cent by 1 mm. of lead. According to Kutherford they are completely a1)sorbed by 2 mm. of lead. The hardest beta rays, after penetrating 1 cm. of e]iithelial tissue, lose about 94 per cent of their energy. In other words, on account of absorption their quantity after passing through 1 cm. of tissue, is only about 6 per cent of that at the surface. The gamma rays are absorbed to the extent of 40 per cent by one cm. of lead and to the extent of 99.4 per cent by 10 cm. of the same material. The gamma rays from thirty milligrams of radium can still be detected by the electroscope after passing through 25 cm. of lead or 30 cm. of iron. According to the investigations of Giraud, gamma rays are reduced to one-half their intensitj^ after passing through 20.4 cm. of water, 18.3 cm. of blood serum, 14.4 cm. of blood or 7.6 cm. of muscular tissue. Using lead as a test of absorbing jjower, liard gamma rays are about thirty times as penetrating as hard x-rays from the Coolidge tube. Using water .(tissues) as a standard of comparison hard gamma rays are slightly more than four times as penetrating as hard x-rays. Advantage may be taken of the fact that the alpha, beta and gamma rays are stopped or absorbed by varying thicknesses of metallic and non- metallic substances. By placing between the radium and the tissues different thicknesses of such materials, varying portions of the beta and gamma rays may be filtered out. The biologic effects of the rays will evidently vary according to the type and quantity of rays that penetrate the screen and are absorbed by the tissues. 3. PRODUCTION OF HEAT Kadium lilierates heat spontaneously and continuously. Compounds of radium maintain themselves at a temperature several degrees higher than the surrouiuling atmosphere. In one hour one gram of radium element spontaneously generates sufficient heat to elevate the tempera- ture of ]3f) gi'ams of Avater one degree centigrade. "Tlie emission of heat from radium and other radioactive substances is in a sense a secondary effect for it is a measure of the energy of the radiations expelb'd from tlie active matter Avhich are absorl)ed by the active matter itself and the envelope containing it." (Rutherford.) The alpha pai-ticlcs ])rodiice the greatest heating effect, furnishing 125 calories of the I'U) calories jiroduced by one gram of radium i)i one hour. The beta rays bcjir 4.5 ;iiiil the Lrainm;) rays n.5 of tho remaining 11 calories. PHYSICAL AND CHEMICAL EFFECTS OF RADUJM RAYS 71 4. EMISSION OF LIGHT All radium coiujioniuls are feebly self-liimiiioiis in the dai'k. This ])henomeiioii is probably due to the preseuce in preparations containing radium of impurities -whieli phosphoresce under the constant bombard- ment of the rays. This luminosity varies under different conditions. Radium pre])arati()ns lose a large amount oC their luminosity upon ex- posure to damp air, but regain it again when the salts are dried. 5. PHOSPHORESCENCE AND FLUORESCENCE Various bodies phos]:)horesce or fluoresce under the influence of radium rays. The large majority of substances that exhibit this property belong to the alkali metals or alkali earths. Among the many different substances that become luminous when exposed to the rays are willeraite (zinc silicate), kunzite and sparteite, barium i)latinocyanide, hexagonal zinc blende, certain kinds of dia- monds, etc. The property possessed by radium rays of inducing phos- phorescence has been taken advantage of by Crookes in devising the spinthariscope. In this little instrument a minute quantity of radium is enclosed in a tube which has a zinc sulphide screen at one end and a mag- nifying lens at the other. Upon looking through the lens in the dark the screen appears as a dark field lighted up by rapid scintillations. The lat- ter are due to the continuous shooting out of alpha particles which cause, by impact, the zinc sulphide to fluoresce. Certain bodies, e.g., fluor-spar, when exposed to radium rays become ■ luminous only Avhen heated — this phenomenon being known as "thermo- luminescence." The alpha rays are the most active in causing fluorescence, the beta and gamma rays being much less powerful in this respect. 6. PHOTOGRAPHIC ACTION All three types of rays have a marked action on the photographic plate, the beta rays being less energetic than alpha rays and the gamma rays less active than either of the others. Radiographs made with gamma rays, however, are better defined than those made with beta rays mixed with gamma. Radiographs made with x-rays are much more clear and distinct than those made with radium radiations. 7. COLORATION OF VARIOUS SUBSTANCES Ordinary soda glass is colored violet or even black after long continued exposure to the rays. Other kinds of glass may become brown or yellow. The capillary glass tubes in which the emanation is confined for thera- 72 RADIUM THERAPY pentic use as well as certain parts of the glass tubing of the emanation apparatus itself thus turn violet after prolonged use. Plates of mica may be colored brown or black. Joly showed that the "pleochroic halos" of mica Avere due to radioactive effects. Diamonds may tem- porarily be colored rose, yellow, blue or green. It was at one time thought that the change in color produced by the rays in barium platino- cyanide might serve as an index to the therapeutic effects of the rays just as x-rays may be measured by the Saboraud-Noire pastiles. No practical results have been obtained, however, from this method of measurement. Coloration effects are due especially to the alpha particles but the beta and gamma rays may also act in producing them. The change in color due to alpha rays is limited to a surface layer, as, e.g., in the case of glass when it is exposed, while the beta and gamma rays color the deeper layers of the substance as well. 8. OTHER CHEMICAL EFFECTS In addition to the coloration of certain bodies just referred to, radium rays, especially the alpha particles, may produce various chemical changes in numerous substances. Only a few of these effects will be mentioned here. Ozone may be produced from oxygen. Various metals, such as lead, mercury, etc., Avhen exposed in air, are rapidly oxidized. Water is decomposed by the radiations into hydrogen and oxygen. Organic matter, in general, is decomposed gases being given off. In the apparatus for the extraction and purification of radium emanation for therapeutic use stopcock grease is not used, owing to the decomposition of the grease by the radiations with the production of carbon dioxide. Paper, rubber and other fabrics exposed constantly to the radiations, crack and become reduced after a time to powder. The flexible type of radium applicator made of linen or rubber becomes more or less dis- integrated after some months and must be remade. Many other chemical reactions due to the radiations have been observed but for details of these and many other interesting phenomena the reader is referred to special works on radioactivitv. CHAPTER IX BIOLOGIC EFFECTS OF KADIUM RAYS EFFECTS OF RADIUM RAYS ON LIVING CELLS Xumeroiis experiments have demonstrated the effects of radium rays on living cells of both the vegetable and animal kingdoms. In this and the sncceeding chapter we shall give the results of some purely experi- mental investigations which have a direct bearing, hoAvever, on the use of radium in disease. 1. Effects on Bacteria Aschkinass and Caspari, Chambers and Russ, Green, Pfeiffer and Fried- berger, Hoffman, Strebel, Strassmann, and many other investigators have carried out experiments to determine the effect of the rays or of the emanation on bacteria. Pf either and Friedberger exposed gelatin cultures of cholera and ty- phoid bacilli and of anthrax spores to 25 mg. of radium bromide at a dis- tance of 1 cm. The beta and gamma rays M^ere used. The growths within a certain superficial area were destroyed in 16, 48, and 72 hours, respec- tively. Strassmann studied the effect of the rays from 10 mg. of radium bromide upon various organisms. The time required to kill B. prodi- giosus, streptococcus, staphylococcus, and B. tuberculosis was found to be 24, 24, 48, and 108 hours, respectively. Chambers and Russ prepared emulsions of various organisms in distilled water. Emulsions of B. coli communis, staphylococcus pyogenus aureus, B. pyocyaneus, B. anthrax and B. tuberculosis were exposed either to a known intensity of beta rays or to a measured concentration of radium emanation. The beta rays from as small a quantity as 7 mg. radium bromide were found to have a bactericidal effect. In estimating the effect of the emanation a known volume of the emulsion of the organism was removed from the influence of the emanation at different periods and planted upon agar-agar. AYith a concentration of the emanation amounting to 5 mc. per c.c, the number of organisms being approximately one million per c.c, a sterilizing effect was noted on the above organisms in periods of from sixty-five minutes to four hours. A possible error in these conclusions lies in the fact that the emanation produces ozone wliicli nuiy be the bactericidal factor. From these and the general trend of many other experiments it has been con- cluded that the rays from radium have distinct bactericidal properties when allowed to act in sufficient doses outside of the l)ody of the host. As to the effect on bacteria in tissues, however, no results have been ol)- tained experimentally that would indicate that bacteria may be actually 73 74 RADIUM THERAPY desti'oyed l)y ladiuin rays without serious injury to tlie tissues them- selves. It may l)e mentioned, however, that Flemming and Krusius ob- served inliil)ition of the growth of bovine tubercle liaeilli placed on the cornea or in the anterior chamber of the eye. In military surgery beneficial effects in checking suppuration in deep wounds have been noted. Improvement has been noted by the writer and others following the inti'oduetion of radium tubes into tuberculous si- nuses, etc. Certain chronic ulcers discharge less freely after radiation. The.se favorable effects are probably to be attributed, however, to the effect on the tissues rather than to the actual bactericidal effect of the rays. With our pi-esont knowledge of the effect of the rays on the higher types of living cells no practical results in the actual destruction of bacteria in tissues without destroying the tissues containing them can be expected. Long before the bacteria, which are highly resistant vege- table organisms, can be destroyed, the more sensitive tissues of the animal organism will ])e irivparably damaged. 2. Effects on Seeds and Plants Abbe, ^[atout, Molisch, Fabre and many others have recorded interest- ing experiments on seeds and plants. Abbe exposed wheat grains to mixed beta aiid gamma rays for different lengths of time and at varied dis- tances. "The universal effect was a depression of growth exactly in proportion to both time and distance." INIatout exposed the seeds of cress and white mustard to the beta-gamma rays for a week and found that they had lost their power of germination. ]\Iolisch exposed the • buds of- syringa vulgaris to the beta raj'S and found that their growth was favored when in the resting stage but hindered when in the growing state. Fabre found that a flowering lily, irradiated Avith strong doses, had its development stopped completely. Further illustrations of the effect of the rays on vai'ious forms of vegetable life may be found in s])('cial articles referred to in the bibli- ography. 3. Effects on the Lower Forms of Animal Life Observations of the effects of the radiations on certain loAvcr forms of animal life (protozoa, etc.) have been made by Dohn, Ilalberstaedter, Willcock, Zuelzi'r and many others. Only a few of these experiments can be referred to here. Ilalberstaedter and his cowoi-Uers radiated trypanosomes and observed ])articularly the effect both on their subse(iuent motility and their power of infecting animals. Willi tlie doses used, the motility of the trypan- osomes was apparently unaffected. The rays checked, however, tlieir power of re])ro(lucti(.)i so that infection did not, as a rule, occur. From tills it was inferred that the rays acted i)aiticidarly on the nuclei which are the elements responsible for the propagation of the trypanosomes. BIOLOGIC EFFECTS OF RADIiai RAYS 75 Halberstaedter, therefore, inferred tliat llie radiations affeeted and de- stroyed the reproductive fimetions of the or«ianisHis before the nutritive functions were injured. Tlie effects on the developing' forms of some of tlie h)wer animals have been ol)served by Bohn, 0., G. and P. Hertwi<>', Tliur, and many others. Bohn investigated the effects on the spermatozoa, ova and larv;e of the sea urchin. Spermatozoa were rendered less active and finally killed. Ova and larvffi developed more slowly and irregularities of development and form were observed. Paula Hertwig iuA'estigated the effect of radiations on the development of the ova of ascaris megalocephala, particularly Avith respect to the nuclear changes. Development was slower than normal and irregu- larities of form were noted. The chromatin of the nuclei was especially aifected and even destroyed. Thur observed the eifect of radium rays upon chick embryos and later upon the embryos of the gold fish. Retardation and irregularities of devel- opment and the production of monstrosities were noted. 0. and G. Hertwig have made an extensive series of observations upon the spermatozoa, ova and larvae of frogs. Sufficiently long exposures disorganized the chromatin of the spermatozoa. Ova that had been fertilized with normal spermatozoa and then irradiated developed much more slowly than normally and ex- hibited many irregularities of development. Ova that were fertilized with irradiated spermatozoa also showed many abnormalities of develop- ment. It is of interest to note that 0. Hertwig found that certain chem- ical agents produced irregularities of development and abnormalities of form that were nearly identical with those due to radiation. Radium cannot therefore be regarded as producing changes in these developing forms that are absolutely characteristic. For a fuller account of these and many other interesting observations of the effects of the rays on various organisms the reader is referred to the articles mentioned in the bibliography. 4. Effects on the Various Tissues of the Higher Animals Broadly speaking, all three types of rtidium rays, if allowed to act in sufficient doses, produce inflammation and even destruction of the ir- radiated tissues. In a subsequent chapter devoted to the subject of ''re- action" we shall refer to two different kinds of response on the part of the tissues that are to be observed after the application of radium to the skin. We shall then (>mphasize the fact that very important modifica- tions of vital tissues nuiy be brought about either by a selective or by an inflammatory effect of the rays. A¥e mention this at this point in order to correct an erroneous belief that radium rays in order to cause pathologic tissues to disappear necessarily cause infiammation. Alost of the histologic examinations of irradiated tissues have been nuide in 7G RADIUM THERAPY cases ill wliieli a more or less intensive iiifiammatory effect had been produced. The "selective" effect of the radiations, resulting in modi- fications of tissue that are not associated with visible inflammation is just as important, however, from a clinical point of view, as the in- flaniniatorv effect. EFFECTS OF THE RAYS ON THE SKIN The maeroscoi^ie or clinical appearance of the intlanimation of the skin due to radium rays will be discussed in the main in a later chapter under the subject of "reaction." Here we may consider the histologic changes occurring- in the skin aftei* experimental radiations. These changes have been observed and described by Halkin, Thies, Guyot, Dominici and Barcat, and many others. The animals used in the various experiments were pigs, guinea pigs and mice. Thies exposed an area of human skin. We may first briefly epitomize the histologic findings of Dominici and Barcat who have accurately stated the conditions of their experiments. These two authors made their investigations with six mg. of radium bromide contained in a "varnish plaque" and spread over a circular surface two cm. in diameter. In one series of experiments no screen M-as used, the radiations consisting, therefore, of mixed beta and gamma rays (beta rays probably 90 per cent, gamma rays 10 per cent). Ten exposures of five minutes each were given on successive days, guinea l)igs being used. The clinical effects appeared ten days later. These consisted of eiythema followed by ulceration and crusting. The crust fell off between the fifth and sixth, week. The healed irradiated area tlicu ajiiieared as a dejiigmented. hairless, smooth and supple scar. Histologic Findings Eight or Ten Days after the Commencement of Exposures In the 0|)i(l('nnis, cviik'nccs nf iunainuuitiou Averc noted. The nuclei of tlic epithelial {'clIs slio^-cd eidargciueut or ii-regularity of outline to- getlu'i- with thickening of the cliroiiuitiu fibrils aiul the nucleolus. Iii- tei-cellulai' edema was ])reseiit. Histologic Findings Ten or Fifteen Days after the Commencement of Exposures Kpideniial (les(|uaiiiat ioii was noted and Ihore were evidences of a granular and pigment a ry deticuerat ion in the .sweat and sebaceous glands and ill the hair follicles. DiiiiiiL;- this same period the corium was the seal of ail intense congestion and of a be' the skull, 55 ms>'. of radium bromide screened with 0.5 mm. of platinum aiul 1 mm. of rubber were placed on the brain substance and allowed to renuiin for two and one-half hours. The velf)p. From this he concluded tliat while the rays acted directly on the tumoi- cells, tlie\- did not actually kill the cells but rather imjiaired llieir i)i-()lirerating ]io\ver. In other word.s, the i-ays acted chiefly on the |)i-opagating runction and to a less extent on tb.e nutritive function of the cell. This observation gave rise to the hxpothesis that the actual 90 BIOLOGIC KFFIX'TS OF RAnir:\I RAYS 91 (leatli of the cmihmm- cells -was l)i'()U 8 times as long- as that, required for beta rays when mixed Avith yamma rays as described iu the previous experiment, h'l-om this obsei-vat ion the authors coucluded that there Avas a lack of shai-pness in the lethal actiou of the o-amma rays as compared with beta rays. It may be uottul, however, that the distance of the radium from the tissiu's was about (1 times as p-reat when (jamma ravs were used alon(> as when beta rays mixed with pamma rays Avere em]ib\ved. Tu still auother series of experiments the authors used 83 mrobably i>romptly removed. Tissue directly nuder the radium tube, but 1.1 cm. a\\a\- from it, yren-. when inoculated into other animals, as \\ell or perhaps better than the controls. As tlie beta rays are absorbed by 1 cm. of tissue, this experinuuit apparently shoAved that the p;annn,a rays from S:! mp. c(uild not destro\- cells "in vivo" in 2 hours, althonph "in vitro" such cells were desti-oyed iu 1 lunir. The following are amonp the conclusions of tln^ authors. 1. The hard beta rays, mixed Avith p-amma rays, have about 8 times the lethal effect of the pure uamma rays on malipuant cells. Inasmuch, hoAvever. as the beta rays are absorbed by 1 cm. of tissue, the panima rays must be used f(n' deep effects. 2. S^ublethal exposures slow the prowth of tunun- cells for a certaiu leupth of tinu' while still shorter treatments seem to stimulate the cellular activities. 3. The dose of radium rays re([uired to destroy tunu>r cells "in vivo" is preater than that lu'cessary to destroy isolated cellular elements. This observation explains the ffU-t that an exposure capable of destroy- inp a small nu'tastatic cai'cinoma nodule in man is (piite ineffective in the case of a well-\ ascularized ])rinuiry carcinoma. EFFECT OF THE RAYS ON HUMAN CARCINOMA The clinical jiart of oui- woi-k deals fully with this topic. It Avill lie of interest, however, to mention hei'c a few experiments Avhich Inne been made to determiiu' the dose of radium rays necessai-y to destroy Ininian carcinoma. F. C. "NVood has nuule some invest ipat ions with reference to the effect p.TOT.onir EFFECTS OF RAr)ir:\r uays 93 of tlie o-amiUfi rays on mctastalie slaratus for the apiilication of radium. A, Silver tube containing 15.21 mg. radium element. Length of tube .16 mm., outside diameter 2 mm., wall thickness ^Ao mm. B, Brass screen, wall thickness 1 mm., to contain tube A. C, Round glazed applicator, Yz strength, 1 cm. in diameter. D, Square glazed apiilicator, ^4 strength, 2 by 2 cm. B, "Toile" wrapped in rubber dam, lAo strength, 3 by 4 cm. from 1.5 to 3 millimeters. For convenience and safety in handling, the capillary glass tubes are usually inserted into silver tubes, just large enough to contain them. The silver tube may have a small screw cap to retain the glass tube and may be hermetically sealed. The wall thick- ness of the silver tube is usually %o ^^- but it may be of any desired thickness or the tube may be made of platinum or any other material. Over these tubes may be slipped screens of different thicknesses in order to filter out varying portions of the beta and gamma rays. 2. Radium Needles, instead of the ordinary tubes, may be used and introduced directly into the tumor tissue. In this type of apparatus the radium sulphate is packed directly into a hollow needle which is fitted with a fine screw cap containing the eye of the needle. The cap is soldered 109 110 RADII^M THERAPY on so tliat tlie radiiiin may ])e completely protected. As much as 12, or more, mg. of radium element may be packed into a needle smaller than an ordinary round surgical needle. Needles are usually made of steel, plati- num or some strong noncorrosive alloy. The wall thickness of steel needles is usually %o mm., the length 2.7 cm. and the outside diameter 1.75 mm. AVhile platinum is nearly 3 times as dense as steel, and a plati- num needle will furnish a])()ut 3' times as much metal screening as if steel of the same thickness were used, the softness of even "hard" iridioplatinum renders this metal less useful. Speaking very generally, steel needles having a wall thickness of %o of a millimeter and con- la in ing 10 or 12 mg. of radium element should not be left in the tissues over eight to twelve hours. The total amount of radium element con- tained in the needles should not be over 50 or 60 mg. unless the physician lias had the experience with the method and the eases are carefully selected. When radium emanation is available, its use is to be recommended instead of radium sulphate on account of certain mechanical advantages and the absence of the danger of losing the radium. As homogeneity of action on all the tumor cells is the ideal to be achieved, it is prefer- able to use several needles of weaker strength implanted in different parts of the growth rather than one powerful needle. 3. Flat Plates, or Plaques, on Which the Radium Salt is Spread. — The plaques may be composed of linen, rubber or nu^tal. Flexible applicators that may be bent and thus adapted to the convexities and concavities of the skin surface may be made of the former two materials. Linen ap- plicators are known as "toiles." The best type of metal applicator is )nade of silver, the radium salt being spread uniformly over a glazed surface which forms the face of the applicator. Lead free glass must' be used. Plaques of this type are known as glazed radium applicators. These have practically replaced the older varnish applicators. The glazed surface a])])licato]-s may l)e made of any desired shape but the surface must l)e flat. Attention must be paid to the degree of concen- tration of "spread radium" as it is evident that different effects are pi-oduced by variations of Ibis factor. Expressed in terms of radium element, which is the common standard in this country, "full strength," "half strength" and "quarter strength" applicators contain, respectively, 5.00 mg., 2.5 mg., and 1.25 mg. of radium elcinciil to llic s(|uaro cm. The sti'cngth of each applicator is always approximate. A convenient type of a])pli('ator is a scpuire ])la(|ue 2x2 cm., and of "half sti'cngth," i.e., containing 10 mg. of radium element. Other ])laf|ues may l)e smaller oi- lai-ger, round or oval, aiul contain less, or more, radium. Screens of any desired thickness may be placed over the face of the plaque just as when tubes are used. Lead or silver screens having THERAPEFTIC APPARATTTS 111 a thickness of Yio, '/ut and 1 mm. are eonvenient. Varied i)roi)ortions of the beta rays may thus be filtered out in order to prevent, when thought advisable, too much action on the superficial layers of the skin. The plaques have the great advantage over the usual capillary glass tubes enclosed in silver of permitting a greater utilization of the beta raj^s. This is desirable in some types of angioma, epithelioma, etc. The plaques also emit a more uniform radiation on account of their plane surface. They are most useful in certain skin disorders, notably angiomata, in which the cosmetic result is important. The disadvantage of the plaques lies in their relatively large size which practically limits their use to the skin surface. AVhen using plaques with metal screens, it is customary to place first over the face of the plaque the desired metal screen. Over the screen 10 or 12 thicknesses of thin paper are tlien placed in order to absorb the secondary rays. In some cases one or more mm, of paper or other nonmetallic material may be used. The whole apparatus is then wrapped in rubber dam and applied to the lesion with adhesive tape, or a bandage. P>. APPARATUS CONTAINING RADIUM EMANATION We have already said that both radium and radium emanation emit only alpha rays which do not escape from the tube containing them. The real source of the penetrating rays is the decay products, radium B and radium C, and especially the latter. When radium salts are confined in a tube the only function of radium itself and its next decay product, radium emanation, is to produce radium B and radium C as fast as these latter decay. It is evident then, that if we can separate the radium emanation from the solid radium and confine it in a glass tube, radium B and C will be produced by disintegration of the emanation and will themselves constitute the source of penetrating beta and gamma rays. In other Avords, the capillary glass tube in which the emanation is confined may be used to radiate the tissues exactly as if it contained radium itself. Inasmuch, hoAvever, as radium emanation decays quite rapidly, falling to % its original amount in 3.85 days, the radiations from this source are not constant as is the case when radium itself is used. Objection to the use of radium emanation alone as a source of thera- peutic radiations has been made on the ground that the relatively rapid loss of activity impairs its value. This objection can easily be met by remembering that few treatments exceed 24 hours in duration and during this time only 16 per cent of the initial activity of the emanation is lost. For the production and collection of radium emanation for therapeutic use at least 1 gram, or more, of radium element is desirable from a prac- tical point of view. The salt used is radium chloride which is dissolved in Walter to which a small quantity of Iiydrochloric acid has been added. 112 RADIUM THERAPY The extraction, purification, and compression into a small bulk of the radium emanation from this solution is a highly technical and compli- cated procedure requiring special apparatus. For the description of the process the reader is referred to a previous chapter. The advantages of radium emanation tubes over tubes containing radium salts are numerous; among them may be mentioned the follow- ing: (1) The minute size of the emanation tubes. It is easily possible to make an emanation tube less than Vio or even ^loo the size of a tube of similar activity containing radium sulphate. (2) The greater flexibility of the armamentarium, since tubes or applicators of any size, shape or strength may be made. (3) The obviation of danger of loss of the radium since the radium itself is not actually used in the therapeutic applications. On the other hand, for certain surface applications and es- pecially in treating many skin diseases radium plaques are preferable to the emanation apparatus on account of their greater convenience, constant dosage and at close range their more uniform radiation. Apparatus designed for the practical application of radium emanation consists of: (1) Capillary glass tubes, in which the emanation is confined. These tubes vary in length from 3 to 20 mm., the outside diameter being from 0.3 to 0.6 mm. They may easily be made of any desired strength. When intended for external radiations, they may contain ordinarily from 5 to 50 mc. each. Emanation tubes of less strength may be grouped together on pads so that the effective utilization of the weakest tubes is possible. "When intended for external radiations, silver tubes are slipped over the emanation tubes as soon as the latter are sealed off from the emanation machine. These silver tubes are open at both ends. They are 16 mm. long. 3 mm. in diameter and have a wall thickness of 0.5 mm. Enclosed in the silver tubes before the active deposit has formed, the emanation tubes may be conveniently handled in this manner with less danger to the operator. The emanation tubes are retained in the silver tubes by a paraffin plug at each end of the latter. The tubes are then set aside for three and one-half hours, at the end of which time the strength of each tube is measured. The silver tubes are distinguished from each other by means of a coating of enamel, of different colors or combina- tion of colors, an ingenious method devised by Failla. A record is kept of the number of millicuries contained in each enameled tube so that its strength may be calculated from day to day. Glass emanation tubes are sometimes used without filters. They may be laid on the surface of a growth or may be used for insertion into tumor tissue. They are often called "bare tubes" or ampoules to indicate the fact that they are used in this manner. The "bare tubes" used for insertion into tumor tissue are ordinarily about 3 mm. in length and have a diameter of about 0.3 mm. They usually contain from 0.5 to 3 THERAPET'TIC APPARATUS 113 me. of emanation. They may be made hy euttinii' np longer emanation tnbes by means of a minute gas flame. As the pressure of the emanation in the tube is less than atmospheric pressure, no emanation is lost by this procedure. Failla has devised an ingenious machine by means of which a glass tube may ])e cut into shorter lengths with great rapidity. The method of using the bare emanation tu])es by inserting them into the tumor tissue is described in a subsequent chapter. "We have devised an instrument for the convenient insertion of ampoules (Fig. 36). (2) Special steel needles, devised by Joly and Stevenson, in which the Fig. 20. — Apparatus for the application of radium emanation. A, Capillary glass emanation tube, length 7 mm., outside diameter 5^o mrn. B, Knameled silver tube, length 1.6 cm., wall thickness v'io mm. to contain glass emanation tube A. C, Brass screen, length 2;/2 cm., wall thickness .62 mm. to contain silver tube B. D. Brass screen, length 3 cm., wall thickness 1.8 mm. to contain silver tube B. E. Hollow steel needle with screw cap, length 17 mm., wall thickness do mm. to contain emanation tube A. Into a similar needle may be packed about 12 mg. radium sulphate, the cap being then hermetically sealed on. F, Hollow steel needle with plunger to contain glass emanation tube A after removal of plunger. The needle may then be inserted into the tumor for the required number of hours. From this needle may also be ejected by means of the plunger a similar but more minute capillary glass emanation tube which may be allowed to remain in the substance of a growth. The author's instrument for the con- venient insertion of glass ampoules is shown in Fig. 36. capillary glass emanation tubes may be placed. The steel needle, con- taining the emanation tube, may be inserted into the substance of tumors. These steel needles have a Avail thickness of 0.3 to 0.4 mm. and a length of from 1 to 2 cm. The needle containing the glass emanation 114 RADIUM THERAPY tube is withdrawn from the tissues after the required length of time has elapsed. Instead of steel, the needles may be made of platinum or any other desired material. In estimating the time of exposure, due regard must be paid to the amount of screening power possessed by the wall of the needle. This method of using needles has been replaced in large measure by the method previously described in which bare emanation tubes are inserted and left to decay in the tumor tissue. In some cases, hoAvever, the use of metal needles is desirable. C. APPARATUS FOR USING THE RADIOACTIVE DEPOSIT The field of usefulness for the active deposit is relatively small at the present time. The active deposit may be utilized, however, in several ways. These are (1) the deposit may be allowed to collect on a small piece of metal such as lead foil. (2) The deposit may be collected on a wire attached to the negative pole of a battery. Radioactive wires may be utilized by insertion into the tis.sues. (3) A solution of active deposit may be used. 1. The Active Deposit Collected on Metal "We have already stated that Avlien radium emanation is separated from the radium and confined in a tube, a thin coating or film of "active de- posit" forms on the walls of the tube and that the tube itself may then be used as a source of radiation, the function of the emanation being simply to keep up the supply of "active deposit." "We may even go a step further. Once the active deposit has settled on the walls of the tube, the emanation itself may be taken away and the active deposit alone may be used as a source of radiations. Under these circumstances, however, the tube is short lived as the emanation is lacking to replenish the active deposit as fast as it decays. If a small piece of metal such as lead foil is enclosed for three to four hours in a container with the emanation, the metal becomes coated with "active deposit" and may be removed from the container and used alone as a source of radiations. Radioactive lead foil has been used principally for the treatment of vernal conjunctivitis. 2. Radioactive "Wires By a suitable arrangement, a platinum wire may be attached to the negative pole of a battery and inserted into a glass Imlb into which the emanation may be introduced. The radium A that is formed from the emanation has a positive charge. It goes, therefore, as Rutherford first ob.served, to the negative electrode and is deposited there. There is thus formed "radioactive deposit" on the wire, the maximum amount being obtained after about three hours. The radiation from the Avire consists THERAPEUTIC APPARATUS 115 of alpha, beta and gamma rays. Just as in the ease of the piece of metal enclosed in the emanation chamber and previonsly referred to, the "ac- tivity" of the wire decays rapidly. As shown by Lyster and Russ, an "active wire" may be of value when introduced directly into the tissues. Under these conditions, the radia- tions do not suffer any loss by absorption in the apparatus such as happens when the ordinary radium emanation container is used. As will be seen by referring to the following table, however, the radioactivity of the active deposit falls to less than half value in one hour. The short life of the active deposit thus curtails its usefulness. Table XIII (After Colwell and Euss.) Rate of Decay of Radioactive Deposit ALPHA EAYS gamma BAYS TIME ACTIVITY TIME ACTIVITY minutes 100 minut es 100 10 " 53 10 96.6 20 " 46 20 88.4 30 " 40 30 _ 40 " 35 40 66.9 50 " 30 50 - 60 " 26 60 38.5 1 hr. .30 niin. 14 1 hr. 30 min. 25.3 2 hr. 00 ( < 7.2 2 hr. 00 < t 12.9 3 hr. 00 ( ( 1.8 3 hr. 00 i t 3.1 3. Solution of Active Deposit The active deposit may be dissolved in water or allowed to collect in a closed chamber on some soluble substance such as common salt which may then be dissolved. The solution may then be injected, sub- cutaneously or intravenously. The method of preparing a solution of active deposit has been described in a previous chapter. CHAPTER XIII DOSAGE A scientific and perfected method of dosage in radium therapy would demand that the rays comino- from each apparatus be carefully measured and directed in accordance with our knowledge of the radiation neces- sary to destroy each normal and di.seased cell complex. These ideal conditions for treatment cannot be completely fulfilled. In the first place we are dealing with the living organism and even if the rays could be measured for each applicator and directed properly the intensity of radiation necessary to produce certain results will var.v to some extent with the individual tissue or tumor that is treated. Within certain limits, however, the proper measuring of the dose of rays is of the highest importance and is the foundation of a scientific therapy. The number of possible arrangements of apparatus containing radium is so great that we must limit ourselves to a discussion of a few types of ap- plicators that are adaptable to a number of conditions. We shall give, however, the results of certain mathematical calculations that are of value in enabling us to estimate the intensity of the radiations from different types of applicators at different distances. In considering the subject of dosage we must distinguish between (a) surface radiations, i.e., radiations that are delivered by placing the apparatus at various distances from the surface of the skin or mucous membranes, and (b) intratumoral radiations, i.e., radiations that are derived from the actual introduction of the radioactive material into tiie substance of tumors. SURFACE RADIATIONS Neglecting for the moment tlie radiosensitiveness of the tissues, the therapeutic effect of radiations depends upon their quality, their intensity and tlie dui-ation of llic cxposun'. The (|uality of tlie radiations depends u|ion the filtration. Tlic intensity of the radiations at a given point depends upon: 1. The quantity of radioactive material. 2. The filtration. 3. Tiie shape of the source, i.e., the method of distribution of the radium on the apparatus. 4. The distance from the source. f). Absorption in the ajijiaratus and in the tissues, f). The seeoudary radiations in the tissues. A iii;ii-k('(l \arialion of any one of tliese factors nalurally filters 116 DOSAGE 117 the effect of llie radiation. AVc may noAv eonsider the effect of each factor. (1) The Quantity of Radium or Radium Emanation in the Apparatus It is evident that, other thiii cm., it is % of the intensity at 1 cm.; at 4 cm., ^4(; ^iit^ so on. The intensity due to a point source varies inversely therefore as the square of the distance. Consequently, if the source is a single tube, a variation in the distance of the source from the surface of even a few millimeters is sufficient to cause an appreciable difference in effect. From the stand])oint of homogeneity of radiation, it is fi'equently desirable to place the radium tube at a distance of a few millimeters from the surface. For example, neglecting absorption for the moment, a layer of tissue, 5 mm. thick, placed 1 mm. distant from the radium tube emitting only gamma ra.vs would receive on the far side, which is 6 mm. distant, Y^c,, i-^v ( %") of the dose received on the near side, which is only 1 mm. distant. If the same layer of tissue were placed 5 mm. away from the radium, it would receive on the far side, which is 10 mm. distant, only y^ (i.e. 5^/10-) of the dose received on the near side, which is 5 mm. dis- tant. It is evident, therefore, that by placing the radium tube at a cer- tain distance from the skin, the different layers of tissue will receive more uniform radiation. In actual practice, this principle, whenever practicable, may be taken advantage of and several millimeters to one or more centimeters of gauze, rubber or wood may be interposed between the metallic screen over the radium tube and the skin, in order to give the desii-ed distance. This material thus serves the double purpose of absorb- ing the secondary rays from the apparatus and also of retaining the radium tube at the proper distance. In order to compensate for the fall- ing off in intensity of the rays due to the increased distance of the radium, proper increase in either the quantity of radium or the dui'ation of the exposure or both of these factors must be made. "When the radium tube is introduced into a small cavity such as the iiitci'ioi- of the utciMis. it is, of course, seldom possible to keep the tul)e more than a few millimeters distant from the tissues. Under these cir- cumstances, the tissue neai'est the tube receives a dose that is frequently excessive i)ii1 in tliis parlicubir situation no ill effects are ordinarily ob- served. On the skin, however, an unnecessary and undesirable reaction would be pi-odnccd if the radium tube is in too close apposition to it. As lias been stated bcfoi'e, when very superficial effects are desired, the radium tu])e may be placed in relatively close contact with the tissue. Great care must be exei-cisod under these circumstances, however, not to prolong tlic duration of the ('x])osuie beyond the proper limits, as a pain- ful burn may be easily pcoduced. As we have seen, when deeper effects are desired, the radium tnhe may advantageously be placed at least a few millimeters away tKnii llie lesion or several tubes may be used simul- taneously at a distaiu'c of several millimeters or centimeters, so as to DOSAGE 121 cover tlie area occupied by the lesion. The latter arranp:ement, wliieh is ordinarily the better one, will be considered in a subsequent section. Tt may be found by experiment that fifty niillicuries, contained in a point or minute tube, screened to absorb all but ■ a+1/2 , '' «-?/0 2.M --^ I ^^ being equal to tn)i — toti . . = . tan . .* .,'. ' If 2/ zero in this ease. where M is number of niillicuries in the tube, I its length. / the distance away. Take ill = 50, Z = .7, / = .29. We get for the intensity at .29 cm., 100 -^ .7 tan , or 433. .7(.29) .58 This is about two-thirds of that permissible. Hence to approximate to the possible distance, try .29 \/% = .236 cm. The intensity at that dis- tance is 100 -» .7 tan =592. .7 (.236) .472 Hence .235 cm. is as near to the skin as one may leave a 50 millicurie tube for an hour. If we accept as approximate the rule that for the same value of distance times the time, Avith the same intensity, the effect is the same, this will also be the minimum permissible time to leave a 25 mc. tube for two hours, a 100 mc. tube for one-half hour, etc., since 25 X 2 = 100 X 1/4. The above rule holds, however, only Avithin certain limits as Ave shall show later on. (b) Several Tubes Let us now consider tAVo 50 mc. point sources. Let us try to give three points on the skin the same amount of radiation. Let us take one 122 RADIUM THERAPY A B v \ N. y / 1 \ y / \ \ y / \ \ / / \ y N / s. / V y \ / \ y \ / N, \ 1 1--' .L- >J Fig. 21. — Diagram showing two radium tubes affecting three different points on skin. point directly below each tube, and the third point halfway between them. Let A and B be the two tubes, J), E, and C the points on the skin. (Fig. 21.) The intensities at D and E will, from symmetry, be the same. Let us assume the intensity at D and also at E to be 600. Then the in- tensity at C due to A is — rr^- That at C due to B is — -— . Now AC = BC AC- BC^ 2 X 50 if the midpoint of DE is C. Hence the total intensity at C is AC^ 100 AC^' J.et'AD — T. DW=X Then A C z= ITD y iTC = 1" +_ 4 '• 100 X^ 1 — • 600 or r= + = ^, ^"' 4 6 The intensity at D due to A is-^ or -^. The intensity at D due to AD- y- T> • 50 50 50 t* IS = — r, J = ,r.2 ^^i ' The sum of these two nitensities is to BD IfW^DE be 600. 50 50 11 + = GOO or + = 12 y2 Y'. + X- r= ¥■ + X' We have therefore two equations. X' Y' + = 1/6 4 1 1 . + = 12 r= Y- +x^ "We can solve these for X- and Y^ and lience get the desired distances AD and DE. "We find for AD, the distance from the skin, .333 cm. and for AB, the distance apart of the point sources, .471 cm. On the other hand, if we use tubes instead of point sources, we find that DOSAGE 123 with tlie distances as given, tlie intensity at D and E amounts to 482. Hence we must approximate as before by decreasino- the distances in the ratio V%- By several such approximations (we need here to correct the ratio as well as \' AD and ^ AB together) we arrive at the values. y/AB Distance from sl\in = .289 cm.; distance apart = .440 cm. The same procedure can be followed for points and tubes at the cor- ners of an equilateral triangle and also at the corners of a scpiare. Tlic results are given in Table X^^ Table XV Theoretic Minimum Permissible Distance from Skin for 50 mc. for One Hour POINT SOURCES DISTANCE FROM DISTANCE THE SKIN APART TUBES 7 MM. LONG DISTANCE FROM DISTANCE SKIN APART Single tube .289 cm. .0 .235 cm. .0 Two tubes .471 cm. .289 " .440 cm. Three ' ' .353 " .612 " 312 ' ' .307 " Four " .375 " .619 " 332 ' ' .595 " If we wish to change the amount of radium, we must change either the time or the distance. If the distance be kept constant, the time should be changed in such a way that the numerical value of the product obtained by multiplying the number of millicuries by the time in hours is kept the same. In general two arrangements of point sources (or of tubes at a distance of more than a few centimeters) are similar in effect (Amount of radiating substance) (Time) when we have the same value tor ,^. ^ r^ (Distance) - for each distance, i.e., for the distance apart of the tubes and also the distances from the skin. Thus if we increase the time from one hour to six, we must, for point sources, increase the distance each in the ratio \/6 etc. Table XVI Theoretic Minimum Perjiissible Distance from Skin for 50 mc for Six Hours Assuming the maximum permissible close as 50 mc. at 1 cm. for 12 hours, the minimum permissible distances for 50 mc. for 6 hours will be - point SOURCES TUBES DISTANCE FROM DISTANCE DISTANCE DISTANCE SKIN APART FROM SKIN APART Single source 7.10 mm. 6.79 mm. Two sources 8.16 mm. 11.53 mm. 7.92 " 11.56 mm. Three " 8.64 " 14.99 ' ' 8.47 " 14.96 " Four ' ' 9.18 " 15.18 " 9.01 " 15.19 " For tube sources, this method gives only approximate results, due to the departure from the inverse square law. It must be especially emplia- 124 RADIITM THERAPY sized, however, that biologically the method of calculation outlined above does not hold true for all intensities and times. The actual biologic effects can only be determined by experience. For small variations of intensity and time the above method is approximately correct. The effect due to a large intensity for a short time is not the same, however, as that due to a small intensity for the correspondingly longer time. We shall refer to this point again in our discussion of the duration of the exposure. From the foregoing, it may he stated that, in general, two equal sources or tubes may be placed Avitli their centers approximately twice as far apart as their distance from the skin. This arrangement provides an approximately uniform tield of radiation at the skin surface. The fore- going rule does not hold, however, in the case of large extended sources as we shall shoAV later on. Three equal sources or tubes may be placed at the corners of an equilateral triangle. Four equal sources or tubes may be arranged at the corners of a square, if we wish to make the intensity beneath the center of the square equal to that under each of the four corners. In the case of the equilateral triangle and the square (3 tubes and 4 tubes respectively) the same general rule holds as in the case of two tubes, i.e., the sides of the triangle and the sides of the square may be approximately twice as long as the distance of the tubes from the skin. (c) Plaques. — Tubes Laid Side by Side It is evident that as the number of tubes is increased the effect approaches A'ery closely to that produced by a plaque, i.e., by a uniform distribution of the radioactive material on a i)lane surface. At a distance of a fcAV millimeters, the plaque source has a slight advantage over the multiple tube source in that the former produces an approximately uniform field of radiation. Tliis uniformity of effect is of considerable importance in the treatment of cosmetic skin disorders, such as angiomata. At a dis- tance of several centimeters, ])()tli types of apparatus have an almost identical effect. AVc may now gi\-(' some illustrations of the relative effects of a few dif- ferent types of a))plicators. For convenience, the gamma ray intensity derived from a point source containing one mg. of radium element at a distaiu-e of one centimeter, is taken as the unit in all of the following calculations. In calculating Table X\'Il each tube was considered as a point. The calculation Avas also made for 25 tubes considei-ing each tube as a line: the result was 0.1)41. a difference from 9.946 of y_,o Pfi' cent. The intensity decreases as the Tiumber of tubes increases, approaching the value for a uniform distribution which may be estimated from the above table as a])proxima1ely 9.8, i.e., a difference of only about 2 per DOSAGE 125 Table XVII Effect of Different Numbers of Tubes Containing a Total Qxjantity of 500 mg. Distributed Over a Plane Surface 10 x 10 cm. Distance from Plane OF Tubes to Point on Axis Is Assumed to be 6 cm. Absorption in the Apparatus Is Not Considered number OF tubes gamma ray intensity at a point on the axis, 6 cm. from the plane OF THE TUBES 1 4 16 25 100 13.88 10.31 9.99 9.95 9.89 cent from the value for twenty-five tubes. The advantage in increasing the number of tubes (i.e., sources) beyond 15 is not immediately appar- ent for a distance of 6 or more cm. from tlie skin. Tallies XYIII and XIX illustrate the difference in effect of a plaque and a point source respectively at various distances. As we have already Table XVIII Intensity of Gamma Eadiation Due to a Circular Plate 4 cm. in Diameter and a Point Source, Eespectively. Each Type of Source Is Assumed to Con- tain 50 mg. of Radium Element. The Intensity Is Calculated at A Point on the Axis of the Plate, i.e., on a Line Per- pendicular to Its Center. Absorption in the Apparatus Is Not Considered. distance in cm. OF the source from THE SURFACE CIRCULAR PLATE 4 CM. IN DIAMETER, CONTAINING 50 MG. RADIUM ELEMENT. (about 4 MG. PER SQ. CM.) POINT SOURCE CONTAINING 50 MG. RADIUM ELEMENT .1 C .4 .5 • .6 .7 .8 .9 1.0 1.2 1.5 1.6 2.0 2.5 4.0 6.0 8.0 10.0 74.8 57.7 47.7 40.7 35.4 31.1 27.7 25.4 22.3 20.1 16.6 12.8 11.8 8.67 0.17 2.79 1.32 .76 .49 5000 1250 555 313 200 139 102 78 62 50 34.7 22.2 19.6 12.5 8.00 3.13 1.39 .78 .50 126 RADIUM THERAPY shown, tlie plaque source and the multiple tube source are practically equivalent, at least at a distance of several centimeters, in the production of a homogeneous field of radiation at the surface. Table XIX IXTEXSITY OF GAMMA EaDIATIOX DuE TO A CIRCULAR PLATE 10 CM. IN DIAMETER AXD A Point Source, Respectr'ely. Each Type of Source Contains 500 MG. Radium Element The Intensity is Calculated at a Point on the Axis of the Plate. Absorption in the Apparatus Is Not Considered DISTANCE IN CM. OF THE SOURCE FROM THE SURFACE CIRCULAR PLATE 10 CM. IN DIAMETER CONTAINING oOO MG. RADIUM ELEMENT (ABOUT 6.36 MG. PER SQ. CM.) POINT SOURCE CONTAINING 500 MG. RADIUM ELEMENT 1 cm. 2 3 4 5 7 10 15 20 25 63.2 39.6 26.6 18.8 13.9 8.24 4.46 2.11 1.21 .784 500 125 55.6 31.3 20 jlO.2 5.0 2.22 1.25 .800 Tables XVIII and XIX show that so far as the axis and direct radiation are concerned, there is little difference in the effect of the two types of sources at a distance of more than 7 cm. Closer than this the intensity due to the point source becomes much the greater. - Hence if the skin is closer than 6 cm. an extended source (i.e., either plaques or a number of tubes) may be used to greater advantage than a point source for deep treatments. If the skin is nearer than 1 cm., as in superficial treatments, the plaque source is particularly advantageous in comparison with a point source. The advantage of the extended or distributed source lies in the fact that it can be put nearer to the skin than the point source, and, while producing the same effect on the skin itself, it gives a greater effect at a point below the surface. Thus, if 20 wei'e the limiting dose for the skin in the above example, the point source must be at least 5 cm. away, while the extended source can be put within less than 4 cm. of the skin. In tlie latter case, the intensity 5 cm. below the skin surface would be 5 for the point, 5.5 for the distributed material, i.e., 10 per cent higher for the latter. For a distance of 3 cm. below the skin surface, the advantage is less than 4 per cent; for 10 cm., about 10 per cent. There are, in addi- tion, certain technical reasons on account of which a distributed or widely extended source is more convenient of application than a point source. Thus it is more practical to arrange on an applicator, that has, DOSAGE 127 e.g., an area of 100 square cm., 10 luLos or plaques each containing 50 mg., than a single powerful tube, containing 500 mg. It is frequently of interest to know the theoretic variation of intensity for plaques of different sizes. In general, for a surface distribution, if one reduces every dimension in the same ratio, keeping the surface density (amount per sq. cm.) con- stant, the intensity at any given point can be found for the new distribu- tion from the intensity of the corresponding point, respectively, in the old distril)ution by multiplying the given distances by the "ratio of reduction." Thus, for a circular disk of radius 5 cm., using 500 mg., the field at a distance of 1 cm. is the same as for a circular disk of radius 2 cm. (5 X .4) using 80 mg. (500 x (.4)-) at a distance of 4 mm. (1 x .4) ; that for a distance of 2 cm. is the same as for the second case at 8 mm. and so on. While from a physical standpoint the intensity may be calculated as outlined above, the biologic effect may not be the same for plaques of different sizes. Table XX shows the variation in gamma ray intensity at different distances due to a square plate, on wdiich 12 tubes are symmetrically arranged, and to a point source, respectively. From a practical point of view, the more superficial the situation of the lesion, other things being equal, the closer to the skin the radium may be placed, and vice versa, the deeper the situation of the lesion, the farther away from the surface of the skin the radium should be placed. In employing superficial radiations, the overlying skin or mucous mem- brane frequently but not necessarily becomes markedly inflamed or even de- stroyed. Inflammatory reaction should be avoided, as a rule, when possible. When employing deep radiations, it is usually desired to preserve the over- lying skin or mucous membrane. Hence, only a slight amount of surface Table XX Gamma Eay Intensities Due to a Single 6x6 cm. Plate, Containing 200 mg. in 12 Tubes. Absorption in the Apparatus Is Not Considered. distance from axis distance prom plate^g cm. distance from plate^io cm. 12 tubes point source 12 tubes point source cm. 4.845 5.556 1.898 2.000 2 " 4.503 5.000 1.833 1.923 4 " 3.670 3.846 1.665 1.724 5 "■ 3.202 3.279 1.557 1.600 6 " 2.775 2.778 1.441 1.471 8 " 2.022 2.000 1.208 1.220 10 " 1.493 1.471 .998 1.000 12 " 1.128 1.111 .821 .820 14 " .875 .862 .679 .676 16 " .693 .685 .566 .562 IS " .562 .556 .475 .472 20 " .463 .459 .403 .400 128 RADIUM THERAPY Table XXI Gamma Eay Intensities Due to Two Such Plates, or Points, Identical with Those in the Previous Table. Distance from Source to Surface^6 cm. The term "center line" is used in considering the effect of two applicators arranged so that the planes containing the tubes are at the same distance from the surface but separated by an interval of space. The center line is the line perpendicular to the plane of the tubes and passing through the midpoint of the line between the centers of the surfaces of the applicators on which the tubes are arranged. Absorption in the apparatus is not considered. distance from center line distance apart of plates = cm. PLATES points distance APART OF PLATES = 4 CM. PLATES POINTS' DISTANCE APART OF PLATES = 8 CM. PLATES POINTS 1 cm. 8.173 8.846 6.445 6.624 4;797 4.778 3 " 7.620 8.334 6.525 7.000 5.163 5.317 5 " 6.525 7.000 6.338 7.027 5.631 6.111 7 " 5.163 5.317 5.631 6.111 5.720 6.418 9 " 3.903 3.889 4.545 4.708 5.196 5.685 11 " 2.897 2.862 . 3.468 3.463 4.232 4.402 13 " 2.186 2.156 2.584 2.556 3.238 3.237 15 " 1.690 1.667 1.956 1.950 17 " 1.338 1.321 Table XXII Gamma Ray Intensities Due to Two 6x6 cm. Plates Each Containing 200 mg. IN 12 Tubes. Absorption in the Apparatus Is Not Considered. Dis- tance from Source to Surface=6 cm. distance from DISTANCE APART DISTANCE APART DISTANCE APART CENTER LINE OF PLATES = OF PLATES = OF PLATES = 2 CM. 6 CM. 10 CM. PLATES POINTS PLATES POINTS PLATES POINTS cm. 7.340 7.692 5.550 5.556 4.044 4.000 2 7.278 7.778 5.692 5.846 4.268 4.249 4 6.867 7.556 5.996 6.471 4.798 4.957 6 5.996 6.471 5.973 6.667 5.378 5.862 8 4.798 4.951 5.378 5.862 5.538 5.241 10 3.650 3.640 4.363 4.531 5.065 5.556 12 2.715 2.685 3.337 3.334 4.133 4.305 14 2.055 2.027 2.485 2.459 16 1.591 1.570 iiitljiiiiniatioii is ordinarily i)roclii('C'd and in most eases it may be avoided al- tof^ether. For certain of tlie most snpei-fieial efifeets, the radium may be placed practically in apposition with the skin or mucous membranes, especially, as we have .shown, when llio sonrcc of tlie radiations is a plane surface. For somewhat deeper effects the distance of the radium from the surface may be from 2 mm. to 1 cm. ; in other cases requiring still deeper effects, from 1 to 6 em. ; for the deepest effects, from 6 to 10 or more cm. As the distance DOSAGE 129 of tlio source froni llic surfaco increases, tlie (luaiitily of radium necessary for certain effVets nnist be increased. AVhile the diminution of intensity due to distance and al)sorption may he partly compensated for by in- creasin')00 mg. in 2o tul)es, at a point on the axis 6 cm., distant from the plane of the tubes, (i..'5'-2. IJy a second metiiod, i. e., using the average distance, GMS. Sample calculation. NO. TUBES EFFECT DUE TO EACH TOTAL EFFECT riliST MKTHOl -(.I+.3) 1 .55') e 1 — -(.1+V- ) .372 .372 2 . 500 e -(.1+V,3 ) . 330 .GOO 2 . .^85 e 10 — (.1+ V '» ) .243 .486 2 .500 e -(.l+_Vn ) . 330 .660 4 .454 e -(.1+Vn ) .295 1.180 4 .^57 e -(.1+Vn ) . 222 .888 2 .384e III -Ci+V. ) .242 .484 4 . 357 6 lU .222 .888 4 .294 e -(.1+Vn ) 10 .17G .704 6.322 SECOND METHOD d d nd 1 6 6 4 2V"To (1 . 324(1 25.298 4 2V 13 7.2112 28.845 4 2VTr () . G332 26.553 8 2V 14 7.4834 59.868 4 2VT7 8.24G2 32.985 25)179.528 20)7.1812 .35906 -.45906 .1 9.941e =6 281 .45906 The difference between the results of the two above methods is 2/3 per cent. Ordi- narily it would be mueli less as in these calculations a small distance has been used. 130 RADIUM THERAPY diieecl without using relatively large quantities of radium. Practical ex- perience has shown that in most cases demanding deep effects a minimum of 500 mg. is required, while in other cases not less than 1000 to 2000 mg. are necessary. In such eases, the minimum amount of metal screening is 2 mm. of brass or its equivalent of another metal, and the distance of the radium from the surface should not be less than 10 cm. 5. Absorption (a) Absorption in the Apparatus. — Let us now consider the effect of absorption in the apparatus in decreasing the intensity of the gamma radiations. For convenience, the gamma ray absorption in the apparatus has been calculated in Tables XXIII and XXIY for a medium of about the density of w'ood, which has an absorption coefficient of approxi- mately .05. There are two possible ways of calculating the eifect of absorp- tion on the radiation due to a number of tubes, as shown in Table XXIII. B.y the first method, the absorption is calculated for each tube separately, and the resulting corrected values of intensity are added together. By the second method, the average of the thicknesses of absorbing material between the radium and the point alfccted is found first, and the sum of all the uncor- rected values is corrected by the amount of absorption which would occur if this average distance held for all ; this second method is only an approximate one, of course. In either case, whether the correction is made for each tube separately, or, using the average distance for all the tubes at once, we mul- tiply the uncorrected value by the exponential e-M. or -^jrx , i.e., just |4 of that at S. Hence, at first siglit, iji order to make the intensity at P equal to that at -S^, one would say that it is necessary to have four portals of entrj^ situ- ated at A, B, C, and D, the effects of which would all combine at P making the intensity at point P e(|ual to that at i)oint N. We find, however, four portals are insufficient since />'. C, and D contribute not alone to the efifect at P but also to that at S. Let us then try five portals. This number proves to be insufficient, and so on up to nine or more portals of entry. $ /)• B C Vig. 23. — Diagram illustiating imiltiplc i)ortals of entry. Tt sliould hi- thfui'ctically |)()ssil)h', by sufificienlly incj'easino- flie luimber of portals to ol)taiii an intensity at /' which wouhl be ' i)()rtals outside one ])lane. and l)y siiitalib' sci'cciiin^. Lei us suppose that all radial ions are sci'cened off except, for each ])ortal, a beam just sufficient [<> radiate the tissue to be destroyed (as- suming no sideways scattering). Then the four portals required by DOSAGE 137 theory Avill Ix' ciiouii'li, ])i'()\i(l('(l tlicy nro placed so tluil the o\'erliii)])Iiiji: of lieaiiis oeeiii's almost entirely in llie diseased tissue, i.e., the portals should not he dianietrieally opposite as in V\iX. -'■'>■ Tt is then ])ossi])le to j^hiee tlu^ ])()i-tals niueli nearer tog-ether. Tiiey must he sufficiently far ajiai't, lu>wever, so that the four heams do not overlap nearer the portals than tlu* tumor at /'. or even that three heams do not overlap except in the immediate vicinity of the tumor. Let us noA\- ])lace an applicator containing- 1000 nic, ai-ranged on a plate (10 X 10 cm.) at a distance of 10 cm. fi-om the skin. T.et us assume that the maximum skin dos(> is ohtained by a])i)lyinsi- it for eighteen houi's, i.e., ISOOO nu-. 10 cm. hours (lOOOxlS). Actual expei-iiiients have proved this latter assumption to he nearly correct. The maximum s]\in dose is thus found under the conditions staled to he ISO me. em. / 18,000 \ l.ours. ^— -j Assuming the ratio of 1.15 of skin dose to eareinonui dose, as deter- 7nined hy Ki'oenig and Friedrieh to l)e corr(>ct, the carcinoma dose that it is necessary to deliver 10 cm. helow the sui-face at a point -which Ave will assume to ])e the site of the tumor, is 15() mc. cm. liours. This dose can he delivei-ed theoretically Avith four ])oi'tals of entry, h\' giving at ea(di portal a i-adiat ion t luit is slightly less than the maximum skin dost'. The al)ove result is easily calculated fi'om the following considerations. According to the inverse s(puire law, the intensity at a distance of 20 cm. is 1^ of that at 10 cm.; hence in oi-der to make tlu' intensity mid- tiplied hy the tiiiu' i)i-oduct at a distance of 20 cm. the same as tluit at 10 cm., we must use four diffei-ent sites of api^lication. The sum of the effects at each ])ortal on the skin will then he etjual to the total effect on the tumor. The ahove cahndation assunu's that tliei-e is no a])sorption in the tis- sues. If we assume an ahsor|)tion coefficient of .05, the effect due to each ])ortal will he decreased in tlu' deej) dose hy e"'; hence, since the sur- face dose is uiuiff'ected, the junnher of portals of entry must he increased l)y e"--"' i.e., 4 e-'' or in other words, about (i portals will he the nund)er I'ecpiired. It is possible, however, that tlu' effect of "scattering" the primary beams, i.e., the eff'ect due to secondary radiations, nearly cancels the effect of al)s()rption. Deep Dose Produced with X-Rays Compared with that Produced with Gamma Rays AVith x-rays, th(> ])rol)leni of delivering the deep dose is even more difficult in sonu' particulars llian \\-ith ganuna i-ays, because of the in- ferior penetrating |)ower of the foi-nn-r. Hence, whatever can he ac- complished with x-rays can also be done with gamma rays providing the amount of radium necessary to i)i-oduce the re(iuired intensities is avail- ]38 RADIUM THERAPY able. If intensities at the skin surface comparahle with tliose producible with x-rays can be produced with gamma rays, the intensities in the depths of the tissues will be far greater wdien radium is the source of the radiations. It is the product of the coefYieient of absorption and the intensity that really matters, however. Radium is equal or even superior to x-rays in the treatment of certain lesions involving the surface layers, because of the convenience of its applications and the closeness Avith which it may be brought to the points to be influenced. This nearness of applica- tion results in a more sharply bounded region being affected. There is also less penetration to points where radiation effects are not desired. X-rays possess an advantage over radium in the fact that a parallel beam is more easily obtainable Avith the former. Table XXVIII Eelativk IxTENsrriEs AND Effects Due to Parallel Beams op X-rays and Gamma Rays Respectively It is assumetl tluit the elTcets of the absorption of equal quantities of l)oth agents are equal. Assume that the absorption coefficient for x-ray s=0. 1.3 ; for gamma rays=0.033. x-rays gamma KAYS DISTANCE INTENSITY EFFECT INTENSITY EFFECT 1 .13 - 1 .033 1 .88 .11 .97 .032 2 .77 .10 .93 .031 3 .68 .088 .90 .030 4 ..59 .077 .87 .029 5 .52 .068 .84 .028 G .46 .060 .82 .027 7 .40 .052 .79 .026 8 ..35 .046 .77 .026 9 .31 .040 .74 .025 10 .27 .035 .72 .024 11 .24 .031 .70 .023 12 .21 .027 .67 .022 1?, .18 .024 .65 .022 U .16 .021 .63 .021 15 .14 .018 .61 .020 20 .07 .009 .52 .017 25 .04 .005 .44 .015 (1) Hence, for the Srime intensity at the surface, the intensity at any point below the surface is greater for gamma rays; the effect, however, is greater for x-rays down to 14 em. depth. (2) For the same effect at the surface, however, Ihc intensity and effects at any point below the sui'face are much greater for gaiiima liiys than for x-rays. The first of the al)ovc stalcmcnls merely has to do with the relative strengths of each source to l)e used. The second is of iiii])ortance as re- uai'ds tile number of sou)'ces (i.e., of ])oi'tals of entry) necessary, and the DOSAGE 139 possTnility of increasinii' (lie dosi' ;i1 pdiiils Ix'low tlic skin to a ji'roater value than at the skin. It is the ratio of the deep dose to the surfaee dose that determines the niimher of portals of entry necessary. In order to make the dose at a depth of 10 em., equal to that at the surfaee, at least four portals of entry are needed for the type of x-rays considered, while two are more than suiBcient for the o'amma rays. At a depth of 15 cm., eig'ht portals of entry for x-rays, and still only two for gamma ra.ys are necessary. Two portals will still suffice for gamma rays at a depth of 20 cm., while fifteen are needed for x-raj^s. It must be emphasized that the above comparison assumes that the beams from l)otli types of sources are parallel. fi. Secondary Radiations Let us now consider tlie effect of the secondary radiations in the tissues in augmenting the intensity of the radiations below the skin surface. It "was formerly ])elieved that the relative intensity of the rays in the depths of the tissues, as compared Avitli tlie surface intensity, depended upon two main factors, viz., the diminution of the intensity with distance and the amount of absorption that the rays undergo in the apparatus and in the tissues. More recently it has been shown that in all mathe- matical calculations of the deej) intensity, tlie secondary radiations re- sulting from tlie impingement of the primary radiations upon the tissues must be taken into account. Gudzent comes to the conclusion, in a con- sideration of this to])ic, that the sim])le a])sor]iti()n laws for radium rays as applied to ordinary matter cannot be applied to living tissue on ac- count of the impossibility of estimating the secondary radiations in the latter. This author states, "it is not correct, therefore, to compai'e the absorption of the rays in A\ater with the al)sorption in the tissues. The amount of energy that is effective biologically is always greater than can be expected according to the simple laws of absorption. According to the calculations of Glocker, with the hardest x-rays that can be technically produced, the estimated or calculated dose may be increased by the secondary radiations in the tissues at a depth of 7 cm. by 43 per cent, and at a depth of 14 cm., by 77 per cent. With the more penetrating radium rays, the percentage will be still higher. In calculations that do not consider the secondary radiations, wrong conclusions will be reached. The deep dose, on account of the reasons just stated, cannot therefore, be estimated by mathematical calculations." Kroenig and Friedrich state, however, that the secondary radiations, produced by the impingement of primary x-rays on water approximate those produced in the tissues. Owv own experiments described in Chap- ter VII lead us to believe that the secondary radiations in tissues may augment the effect of the primary gamma rays by as much as 70 per cent. 140 RADIUM THERAPY If this be true, it lessens materially the diniiiuition of intensity due to absorption. The Duration of the Exposure Surface exposures may last from a few minutes to twenty-four or more hours. The shortest exposures are given as a rule with unscreened radium. Under such circumstances, beta and gamma rays take effect. The longest exposures are given as a rule with heavily screened radium, the gamma rays only being effective. Examples of the length of therapeutic ex- posures are given in a subsefjuent section. The term "milligram hours" or "millicurie hours" was introduced by Dawson Turner to exuress the duration of the exposure. By these terms, we desi.Q"nate a number Avhicli is obtained l)y multiplying the numl)er of mo-, of radium element or of millicuries of emanation bv the number of houi's of exposure. AVe may neglect for the moment the decay of the emanation. Thus, 10 mg. or 10 mc. or emanation, employed for ten hours, would be expressed as ''100 milligram" or "millicurie hours." These terms are not altogether satisfactory because of their relative in- accuracy and inadequacy. Thus the terms are without great significance, when expressing sui-face radiations, uidess the other known factors that enter into the dose, i.e., the screening, the shape of the source and esDceially the distance — are also stated. A marked variation of any one of this latter group of factors alters the significance of the number of milligram or millicurie hours of exposure. For example, at a distance of 1 cm., 100 mg., concentrated at a point and applied for 10 hours will give a vei-y different effect from the same quantity concentrated on 100 sq. cm. and applied for the same length of time. The same number of mg. hours of exposure, i.e., 1000 may be said to have been given in both instances, liowever. Another element of inaccuracy consists in the fact that the quantity multiplied by the time is relatively accurate only within certain limits. Thus, at identical distances, 100 mg., contained in a minute capillary tube, applied foi- one hour, and one milligram contained in a similar tube and applied for 100 houi-s, will gi\'e different effects and yet the numl)er of mg. hours of exposure— i.(\, 100 — nuiy be said to have been given in both eases. The biologic changes in the tissues during the longer exposure are pr<)l)a1)ly i-esponsible for the difference in the ob- served effect. This bi'ings up tlu> (juestion of Avhethei- the biologic action is the same if one employs a large intensity for a short time or a smaller intensity for a longer time. According to Kroenig and Friedrich's experiments with x-rays, if the ratio of intensities employed is e(iual to 1 to 5 the degree of a biologic action for the same dose is independent of the in- tensity. For ratios greater than 1 to 5 the degree of the biologic action for the .same calculated dose is greater for the greater intensitv. Accord- DOSAGE 141 iiig to tlieso authors, therefore, if we assume tliis statemeut to hold for radium, it may be roughly estimated that 20 mg-. applied for ten hours Avould give approximately the same biologic effect as 100 mg. applied for two houi's, ]irovided the other conditions of the application are iden- tical. In both cases, 200 mg. hours would l)e the calculated dose. On the other hand, 20 mg. applied for ten hours would give a less intense effect than 200 mg. applied foi' one hour, although in both cases the dose may be stated to be 200 mg. hours. Practical experience has shown that the biolog- ical effect is ]U)t the same for large variations of the time and intensity. It should be possil)le, however, to determine more accurately the biologic effect of variations of these two factoi's by a sufficient number of experi- ments. *'The physiological effect of the radiation must depend largely but not entirely upon the total ionization produced during the treat- ment per unit volume of tumor, which is sid^stantially a measure of the energy absorbed. It is evident then that the intensity of radiation at the point we want to affect and the time of exposure are equally important. But we can produce the same total ionization by a small intensity of radiation and a long exposure or vice versa and the question is whether it makes any difference physiologically Avhich method we use. "For small variations, it makes no appreciable difference if the time of exposure is increased in the same proportion that the intensity of radia- tion is decreased or vice versa. But if we increase the intensity 100 times and decrease the time 100 times we cannot expect to obtain the same result as before. Apparently then there is an optimum intensity of radia- tion coupled with a definite time of exposure but, unfortunately, the relation between the two varies with the nature of the tumor, etc.. and cannot be determined except by experience.'' (Failla.) In spite of their limitations and relative inaccuracies we believe that the expressions "milligram" and "millicurie hours" serve a useful purpose and should not be discontinued. When these terms are used, however, the other factors already mentioned that are of importance in estimating the dose should also be stated. As the third factor of most importance is usually the distance of the source from the surface, I would suggest that in the use of the terms "milligram" and "millicurie hours," the distance in centimeters be stated. Thus, one may say, 100 milligram-centimeter-hours or 100 milligram-10 centimeter-hours, the first expression meaning that at a distance of one centimeter and the second that at a distance of 10 cm., 100 nig. hours were given. Millicurie Hours While the nuinlx'i- of "milligram hours" may be easily found by mid- tiplying the number of mg. used by the num))er of hours of exposure, the problem is not so simple when one wishes to compute the number of "millicurie hours," on account of the decay of the emanation, which 142 RADIUM THERAPY loses approximately 16 per cent of its activity each twenty-four hours. It is of importance, therefore, to determine the amount of emanation with which it is necessary to start a given interval (treatment) in order to have a given mean value during tliat interval. This is shown in Table XXIX. Table XXIX TIME OF APPLICATION VALUE, I.E., NUMBER OP MILLICUPJES IN HOURS NECESSARY TO START WITH IN ORDER TO HAVE MEAN VALUE OF 100 ' 1 100.4 2 100.75 3 101.1 4 101.5 5 ■ 101.9 6 102.3 7 102.65 8 103.0 9 103.4 10 103.8 11 104.2 12 104.55 13 104.95 14 105.3 15 105.7 10 106.1 17 106.5 18 106.9 19 107.3 20 107.7 21 108.1 22 108.5 23 108.9 24 109.3 30 111.6 36 114.2 42 116.5 48 119.1 In most cases it is sufficient to take the reciprocal of the value which the strength will take at tlic middle of Hie period of application. Thus for 48 hours to take 100 . 100 value present 24 hours later ' '' q - ^ic.oo-r.ar,) or, approximate! v, _ - = 0/5 x 100 = 120 5/6 This holds nun-e accurately for a shorter period, less accurately for a longer one. We may now give a few illustrations of dosage. DOSAGE 143 1. Superficial Radiations Radium Salts in Plaques. — For many skin diseases, % strength appli- cators may be nsed. It is convenient to have four applicators which may be laid side by side to form an area of 16 square centimeters. The total quantity of radium element in the four applicators is thus 20 mg. With this type of apparatus, a caustic dose may be easily and even inad- vertently given if no screen is used and the time of application unduly prolonged. For the most superficial effects, one may give an exposure, if the apparatus is unscreened except for the rub])er dam in which it is wrapped, of from three to five minutes. Such exposures should not l)c repeated more than two or three times in the course of a week. Such treatments are adapted to superficial skin diseases. For skin disoi-ders that are somewhat infiltrated and require deeper effects, the apparatus may be screened with 0.1 mm. of lead and an ex- posure of from one to fonr lionrs in several periods may be given. For the production of still deeper effects, the apparatus may be screened with a layer of lead 1 mm. thick and an exposure of six or more hours in several periods may be given. In all the above ex- posures, the apparatus may be applied in close contact with the skin. If the screening is 2 mm. of brass and the distance from the skin is in- creased to 1 cm., an exposure of forty-five hours in three periods may be given. Radium Salts or Emanation in Tubes. — For superficial effects, 50 mg. or mc. may be concentrated on an area of from 4 to 6 square cm. The screening may consist of a layer of silver .5 mm. thick plus a layer of rubber 2 mm. thick. An exposure of from three to four hours may be given, when small areas such as from 4 to 6 square cm. are treated. For the production of somewhat deeper effects, the screening may be increased to 1 mm. of silver plus 1 em. of rubber or wood. An exposure of twelve hours or more may be given when small areas such as 4 to 6 cm. are treated. 2. Deep Radiations For deep effects, plaques or tul)cs containing radium salts or tubes of radium emanation may be used. For influencing deeply seated tumors, exposures lasting from ten to tliirty or more hours in periods of ten or more hours each are suitable. The radium plaques or tubes may be arranged side by side on a plane surface having, e.g., an area of 100 square cm. The routine screening in these treatments is 2 mm. of brass or its equivalent of another metal. The radium is placed at a distance of from 6 to 10 or more cm. from the skin surface. The use of not less than 500 mg. or mc. is necessary in most eases; in other cases not less than 1000 mg. or mc. should be employed. If 500 mg. or mc. are used, a 144 RAr)^^^r therapy total exposure of 25 hours at a distance of 6 em. may he g-iven in two or more periods. At a distance of 10 cm., a total exposure of 36 hours may he oiven in two or more periods. With 1000 mg. or mc. under the same .■(.iiditions. 12' ;j liours may he ^iven at a distance of 6 cm.; 18 hours at a distance of 10 cm. If emanation is used, due allowance must he made for its decay. The exposures may he ^iveii in two or more periods. INTRATUMORAL RADIATIONS In some cases, as has heeii said Ix^fore, tlie radioactive material may he inserted directly into the tumor tissue. Radium salts in metal needles mav ])e used for this ])ui-pose or radium emanation contained in metal needles or glass ampoules may he employed. I usually prefer radium emanation in glass amiioides. At the present time, tlu> exact dosage employed in metal needles is largely a matte i- of experience and judgment on the part of the oper- ator. Speaking very generally, 5 steel needles having a wall thickness of 0.4 mm. and cacli containing as nuich as 10 mc. of emanatimi may he Tablf. XXX SiT(!(!i:sTiNa Doses (.Ianf.way) That ]\r.\Y he Used Whex Rake Emaxatiox Ajipoui.es Ake Ixsektep ixto Tumors ror circular a.nl) al'l'koxlmately oval tumors of the same loxo plxmeter DLVMETER 1 tni. l^/2 cm. 2 cm. 2 1/2 om. '^ (111. 4 cm. 5 cm. (5 cm. DEEP IXFU.TUATION Xot iiuiro tlKiii li-> cm. Between 1 and 2 (m. Between 1 and 2 cm. Bet^veen 1 and 2^2 cin. Between 1 and » cm. SURFACE AREA DOSAGE .1 1 sq. cm. u mc. 1.7 8 " 3.14 10 " 4.S 15 " G.ry 17.5 mc. 12.5 20 " 19.3 22.5 " 28.27 25 " FOR SPHERICAL TUMORS THERE IS LITTLE DIFFERENCE DU.METER AREA OF PLANE NO. OP CUBIC DOSAGE OF DIAMETER CENTIMETERS 1 cm. .77 .sq. cm. .52 c.c. 5 mc. 11- cm. 1 . 1 1.70 8 2 cm. 3.14 4.18 10 2V2 em. 7.8 8.19 15 3 cm. G.5 14.08 20 4 cm. 12.5 33.44 00 5 cm. 10.3 65.29 25 () cm. 28.27 112.86 30 7 cm. 3S.4S 251.52 35 8 cm. 50.26 40 DOSAGE 145 left in the tissues six lioiirs. In all eases needles sIiotiUI not he inserted nearer to eaeli other than 1 to 2 em. Prior to Bagg's experiments, which have already heen referred to, the dose used in the insertion of the glass emanation amponles was larger than we now emjiloy. This author's experiments have shown the ad\'isal)i]ii y of using relatively small doses. In dealing with smaller growths, it is sometimes advisahle to increase the dose suggested hy Bagg. We frequently employ in treating the smaller growths 5 mc. of emanation per c.c. of tumor tissue. This amount of emanation may be contained in several ampoules. When treating the larger growths, 0.5 mc. per c.c. of tissue may be sufficient, when the total amount of emanation equals from 25 to 30 mc. When the latter quantity of emanation is used, a larger amount of "cross firing" from the different tubes naturally takes place than A\hen smaller quantities of emanation are employed. Methods of Decreasing and Increasing- the Radiosensibility of Tissues. — The question naturally arises Avhether it may be possible especially in deep therapy to make the skin more insensitive and the tumor more sensitive to the radiatioiis. Schwarz has demonstrated that the radio- sensibility of the skin is dependent to some extent on its plethora. In order to create an anemia of the skin and thus render it less sensitive, this author used com])ressJon of the surface l)y thin wooden plates and showed that the skin was able to stand without injury doses of radium that otherwise injui-ed it. H. E. Schmidt and others have confirmed this observation. Tveicher and Lenz have suggested that a diluted adrenalin solution be injected into the skin in order to render it anemic. Chris- toph Mueller-Immenstadt has used high frequency currents for the same purpose, lie states that this procedui'c not only desensitizes the skin, but renders the underlying tumor more sensitive because of the coincident plethora produced in the tumor. This observation has not yet been confirmed. Several authors have endeavored to sensitize tumors by means of injections of different chemicals, such as eosin, etc. Werner injected lecithin and cholin into tumors 'for the same purpose. The injection of the various substances just named has not led, however, to any practical results. (iauss and Lenu-ke, INrucller-Immenstadt and others have suggested that by injecting into tumors substances of high, atomic weight, .such as electrocuprol, cuprose, etc., the formation of secondary rays in the tissues might be increased. Halberstaedter and CJoldstuecker radiated trypanosomes Avhich had been immersed in colloidal metal solutions and showed that they had become more sensitive to radiations than the controls which were immersed in salt solution. It is hoped that future researclH\s may widen the scope of these ex- periments. Up to the present time, however, the attempts at desensitizing the skin and sensitizing the tunuu' have not proved of any utility in actual practice. CHAPTER XIV THE TECHNIC OF RADIATION It is manifestly impossible to give a complete description of all of the methods of applying the apparatns for the various objects of radia- tion. We may, therefore, limit ourselves mainly to a discussion of the different principles involved. It is important that the operator should have the requisite knowledge of the amount of radium in the apparatus, the quantity and quality of the rays passing through the screens, and the effect on the skin at the given distance. There must also be a clear understanding of the object of the radiation. The kind of tissue that is to be treated or destroyed together with its situation and extent must be known as far as possible. (a) SURFACE RADIATIONS 1. Superficial Radiations The lesion to be treated, if superficial and on the skin, may be gently cleansed if necessary and the rubber, wood, gauze or other material of l^'ig. 24. — Tliis pliotograph shows the metliod nf haiulliiiij; raciuiin. A ratlinm tube is being inserted into a screen. the thickness i-ecpiired in order to keep the radium at the proper dis- tance mjiy then 1h' jipplied and held in place l)y adhesive tape or a bandage. The rndinm ])laqnes or 1ul)es, singly or in combination, may then be laid upon llie material eovei-ing Ibe lesion and held in position in the same Avay. Protection fi'om tlic discharges from a moist lesion is always assured for Ihe api)aratiis l)y wi-a])ping it in a finger cot or dental rubber dam, 146 THE TECHNIC OF RADIATION 147 In the treatment of a lesion of the mncons menihranes, the tnl^es may be attached to a wire or other carrier, covered with the desired thickness of rubber or gauze and then, after being encased in a finger cot, applied directly to the lesion. In order to protect the normal tissues adjacent to a lesion on the skin, one may use a sheet of lead 2 to 4 mm. thick in which an aperture is cut to fit the lesion. This lead absorbs 8 to 15 per cent of the gamma rays and while it does not, of course, protect the normal tissue completely, it ai¥ords a relative amount of protection that is ordinarilv sufHeient. It must be remembered that if the radium Fig. 25. — Forceps 30 cm. long for liandling radium tubes. tube is held at a dista)ice of several millimeters from the lesion by the lead protector, this distance must be taken into consideration in estimat- ing the dosage. In accordance with the law of iuA^erse squares, the in- tensity of the rays from a single tube diminishes very rapidly as the distance of the tube from the lesion increases. For the relative protection of the eyeball in epithelioma of the eyelid, we use a specially constructed gold screen, made after the model of an artificial eye. It is always desirable if possible to protect hairy regions, such as the eyebrow, from the action of the rays. For applications to the dii^erent natural cavities of the body, various methods may be used to suit the requirements of the case. Fig. 26. — Three pronged forceps 30 cm. long for haadling radium tubes. In the vagina or uterus, gauze packing suffices as well as anything for holding the tubes in position. Heavily screened tubes placed against the cervix will not ordinarily injure the healthy adjacent vaginal mucous membrane if sufficient packing is used to separate the walls of the vagina to the fullest extent. "Distance" in addition to the screens on the radium protects the healthy tissue sufficiently. In the nose, mouth, esophagus, rectum and bladder, the tubes may be attached to a plia])le silver wire which can be bent to the required angle and fastened to the adjacent skin. In addition to the wire it is always advisable to have the radium tube anchored by a long silk thread which is 148 RADIUM THERAPY O o V — E^ THE TECHNIC OF RADIATION 149 also fastened to the iieighboriiiji' skin by adhesive tape. This procedure is a precautionary measure in case the wire should break. For the protection of the rectal wall opposite to a circumscribed car- cinoma of the organ, avc insert a finger cot which may be distended with air by a catlieter. In this case, also, distance protects the healthy, bal- looned out, mucosa. For some years, especially in moutli cases, we have made use of the dental modeling compound suggested by Janeway. This material can be fashioned to suit the outline of any growth that is accessil)le and the tubes may be laid in little troughs in the compound. By this device, Fig. 2S. — Screen hoUiers. These instruments are of two different sizes and enable the technician to grasp the cylindrical screens containing the emanation tubes. One end of a screen is shown inserted into the holder. A similar holder (not shown in the photograph) grasps the other end of the screen. The technician may thus screw the two parts of the screen together, without allowing the lingers to come in contact with the radiinii tubes. the tubes may be licld in jxjsition without mucli discoiiii'ort to the pa- tient for the required length of time. The amount of radium to be used in sui)erficial t rcjilinenls naturally varies witli the purpose of the radiation. For example, if a tumor is very small and superficially situated on the skin, a plaque of radium containing as small a quantity as 10 mg. may sometimes be used. The beta rays from such a plaque may be uti- lized by employing little or no screening. The plaque may be placed in direct contact with the lesion or at a distance of a few millimeters from it. ^ I'ig. 29. — Same apparatus as in Fig. 28 but of smalicr size. When dealing with larger superficial growths on the skin 200 or more milligrams may be required. The radium may l)e contained in plaques or tubes that are screened with 1 mm. of silver or its equivalent and may be separated from the lesion by 1 cm. of rubber or wood. For epithelioma of the mucous membranes, it is seldom wise to use less than 200 milligrams of radium element or mc. of enuuiation. In using the technic suggested above, more or less local inflammatory and even destructive action may be produced by the radium, although certain lesions may retrogress without macroscopic evidences of in- flammation. The biologic effect of the radiation naturally depends on the technical 150 RADIUM THERAPY conditions of the application, i.e., the quantity of radium, the shape of the applicator, the screening-, the distance and the duration of the ex- posure. The frequency of repetition of superficial treatments depends, of course, on the dose employed. Exposures may be given daih' or on alternate days or twice "sveekly, etc., depending on all the circumstances. Fig. 30. — Flat silver screens with caps, devised for holding from 2 to 6 enamel emanation tubes. These screens are 2 cm. long, 4 to 16 mm. wide (outside dimensions), and vary in wall thickness from 0.5 mm. to 1.5 mm. 2. Deep Radiations In postmortem examinations of cancer of the cervix which had been treated by placing radium in or against the cervix, Bumm found that cancer cells were destroyed up to a distance of 2^2 to 3 cm. from the radium tube. At a distance of 4 cm., vigorous carcinomatous cells in groups as large as peas or cherries were found in the parametrium. Be- yond 5 cm., cancerous lymph glands were found that were not affected. As a result of these observations, Bumm's dictum that radium has an effective area of influence of not more tlian from 2 to 3 cm., was widely accepted. According to the earlier f>bservations of Wiekham and Degrais, radium rays may penetrate effectively to a depth of at least 9 cm. Kroenig has recently stated tliat it is possible to radiate successfully a carcinoma of the cervix uteri through the abdominal wall, i.e., the THE TECHNIC OF RADIATION 151 raj's penetrate effectively to a depth of at least 10 cm. Kelly and Burn- ham and many others have successfully radiated mediastinal and ab- dominal tumors. In such cases it may be estimated that the rays pene- trate to a depth of at least 10 cm. Kroenig and Gauss have stated that the rays from 500 mg. of radium element that is distributed on a plate apparatus placed at a distance of 6 cm. from the skin may penetrate etfectively to a depth of from 14 to 16 cm. It is evident that Bumm's dictum, that radium rays will not pene- trate effectively into the tissues to a distance of more than from 2 to 3 cm., must be given up. Under certain conditions, such as existed in Bumm's cases, his conclusions Avere undoubtedly correct. For example, in the treatment of cancer of the cervix uteri, even though the quantity of radium be very large and the duration of the treatment prolonged, the Fig. ,^1. — Tanilcin gold screens for holding one or more enamel emanation tulies. These screens have a universal thread so that a radioactive rod of any desired length may be made. The proximal end of the api)aratus is attached to a long flexible silver wire. Length of each screen 2 cm., outside diameter 4 mm., wall thickness 0.8 mm. 3^^ Fig. 32. — Platinum screen for containing a glass emanation tube. A long silver wire is screwed into the end of the screen so as to facilitate its introduction into small cavities. Length of platinum screen 2 cm., outside diameter 2 mm., wall thickness 0.5 nun. Fig. 33. — Screen for inserting radium tubes into the esophagus. The bulb on the distal end may carry a silk thread for guiding the instrument. A "screw-nut" slides on the wire so that the distance from the applicator to the patient's teeth may be easily maintained. effective raying of distant cancerous masses by means of a tube placed within the cervix may be practically impossible. Long before cancer cells situated near the Avails of the bony pelvis, (i.e., about 6 cm. distant from the tube) would be seriously affected, an enormous overdose would be given and a dangerously destructive action might be produced on the tissues adjacent to the tul)e. On the other hand, if a (|iuintity of radium sufficient to give an ade- quate intensity is properly distributed on a plane surface of sufficient size and is placed at a sufficient distance from the lesion, the depth to which the rays Avill effectively penetrate without untoward effects may be enormously increased. There is abundant evidence that indicates, as has been shown in the previous chapter, that by this method of pro- 152 RADIUM THERAPY cedure it is possible to radiate any part of the body Avith an intensity of rays powerful enough to destroy malignant cells, however deeply situated. By using different portals of entry, almost any part of the body may be brought, for purposes of radiation, within a distance of from 10 to 14 cm. from the surface of the skin. The limitations of radium therapy, therefore, are not those imposed by the inability of the rays to penetrate with an adequate intensity to a sufficient depth, but rather by the fact that serious injury to normal structures may be caused by the delivery of too large a dose of deep rays. It must be especially j.-jjr, 34. — Radium pad composed of "squares" of soft wood. The interior of the package is stutYed with cotton, nimensions of pad lOxKTxIO cm. Fifteen screens containinR radium emana- tion tul)es are lield in position on the pad liy adiiesive plaster. This type of apparatus is used fur deep K-'unma radiation of hirge tumors. emphasized that, for adciiuale det'i) efrects, a considerable (juantity of radioactive material must be used — preferably not less than from 500 to ]()00 or more milllgrjiitis of radiuni element or millicuries of emanation. In some cases, 2()()() nig. or nic. arc desirable. While the relatively slight intensity from smaller (luanlitics, such as 300 milligrams, can be to some extent compensated for by prolonging the exposure, practical experience has shown that in most cases the best effects ai-e o])tainal)le only by using the larger quantities for a shorter time. THE TECHXIC OF RAOIATIOK 153 For tlie treatment of deeply seated tumors or other pathologic tissues, when the overlj-ing skin or mucous membrane is to be preserved, pads or packages of various sizes are used in order to give the desired distance. These pads are made up in advance to suit the individual case by using a number of small square blocks, made of soft wood, balsa wood, cork or hard rubber. A suitable size for these blocks is 2x2x1 cm. The blocks may be fastened together by adhesive tape to form various sized Fig. 35. — The uip]ier iiliotograph shows the needle holder devised by Dr. O. T. Freer. A metal needle containing a glass emanation tube is shown in the end of the holder. After insertion into the tumor tissue, the needle may be withdrawn when the retiuired exposure has been given. The lower photograph shows, the instrument devised by Dr. Freer to facilitate the withdrawal of metal needles from tumor tissue. The silk ligature attached to the needle may be engaged in the groove on the end of the instrument. Traction on the needle may then be easily made without damage to the tissues. packages. On account of the joints formed by the tape, even the larger pads have a certain degree of floxibility. On these packages or pads the tubes are placed in parallel rows or in accordance with any desired ar- rangement. The tubes may l)e held in place by strips of adhesive tape. Fig. 36. — Author's instrument, constructed on the ]ilan of an ordinary syringe, for burying emanation ampoules. The obturator, sliding in the lumen of the needle, enables one to cjeci the ampoule into the tumor tissue. The size of these large packages \ai-ies in acc(trdaiice with the lesion to be treated. AVe frequently use packages having the dimensions of Gx6x6 cm. or 10x10x10 cm. (See Fig. M.) In oi-der to reduce the Aveight of the larger wooden ])ackages and to minimize the amount of gannua ray al)sor])tion in the aj)pli('ator, we till the center of each package Avith cotton, the small wooden blocks forming merely the outside or shell of the package. In applying the packages carrying the radium, the so-called "cross 154 RADIUM THERAPY fire" method suggested by Wickham should be utilized to the utmost. In accordance with this principle, subcutaneous tumors are attacked from as many different angles or sides as possible, in order to deliver the greatest possible volume of rays to the deeper parts of the growth and at the same time spare the overlying skin. The periphery of a tumor is always attacked first. As we have pointed out in the previous chapter, Fig. 37. — lU-avy cast-iron movable shield for the i)rotection of the operator. in order to produce a uniform field of radiation at the skin surface, the radium packages in which the radium is 6 cm. from the skin should be 4 cm. apart; if the radium is 10 cm. from the skin the packages should be 6 cm. apart. OthciAvise some sort of a sliield sliould be used in order not to give an overdose to a single skin area. If large and deeply seated tumors, such as may occur in the neck, THE TECHNIC OF RADIATION 155 breast, abdonu'ii, pchis, etc., are present, there should ])e used for the radiations not less lliau 500 to 2000 or more milli;ii'anis or niillieuries. The radium sliould l)e placed at a considerable distance, e.g., ten or more centimeters from tlie skin. The tubes or plaques may be evenly arranged according to the desired method of distribution on one side of the Avooden package just described. The opposite side of the package is placed on the skin. All of the requirements of proper distril)ution of the radium, its distance from the skin, etc., may thus be fulfilled. In addition, every area of skin from Avhicli the tumor can be attacked should be homo- geneously radiated as we have just described. By this method of procedure, a deep gamma ray effect is produced, but there is little or no local inflammation of tissue next to the applicator, if the duration of the exi)osure is correct. Employing 1000 mg. distributed over an area of 100 sq. cm. and placed at a distance of 10 em. from the surface, the safe limit of skin toleration is about 18 hours. If 2000 mg. are used, 9 hours may be given. This exposure may be divided into two or more periods. An interval of several days should elapse between each period. It must be emphasized that the above dosage cannot be repeated with impunity because of the deep effects on normal tissue. A second course of treatment, given six wrecks later, should not consist of over 5000 mc. or mg. hours. These doses were suggested by Jaueway and Failla and they accord in a general way with my own practice. In using adhesive plaster to bind the radium packages to the skin, it must be remembered that the epidermis that has been rayed heavily is unusually sensitive. Superficial excoriations may easily occur and may become a source of great annoyance to the patient. Oreat care should be employed therefore in ai)plying and removing sticking plaster in such areas. (b) "INTRATUMORAL" RADIATION (1) The insertion of radium salts or radium emaualion in metal needles into the tissues. In the use of metal needles the following precautions should be ob- served: (1) An aseptic technic is necessary inasmuch as screened radium does not have a marked antiseptic effect. (2) Several needles of moderate strength should, if possible, be used, rather than one strong needle, in order that an even distribution of the rays may be produced in the entire growth. (3) It is important that a certain quantity of healthy tissue should surround the growth in oi-der that repair may be accomplished. (4) The quantity of radium embedded in a growth depends upon the size of the tumor and the thiekness of the needle wall aud to some extent upon the situation of the growth. Encapsulated organs, such as the tonsil and 156 KADIUM THERAPY the prostate, are especially suitable for needling. The needles should not be inserted into normal tissue. (2) The insertion of bare glass ampoules containing radium emanation into the tissues. The method of treating tumors by the insertion of bare glass emanation tubes or ampoules is one of considerable promise. Indeed it is not too much to say that this method has almost revolutionized the treatment of certain localized tumors. The method appears to have been suggested first by Duane. It has been employed extensively by Janeway and his coworkers at the ]\Iemorial Hospital in New York, by Kell.v and his as- sociates in Baltimore, by the Avriter and many others. The glass emanation ampoules tliat are used are ordinarily about three millimeters long and 0.3 mm. in diameter. They may be inserted into the tumor in proper cases and allowed to remain in sitti. Over 1)0 per cent of the activity is lost in two weeks and they decay practically to zero in about forty days. Each tube during the entire time of decay gives a dose that may be expressed in millicurie hours by multiplying 132, i.e., 5^/4 tlays, ^y the number of millieuries originally in the tube. We assume in the foregoing calculation that the tube has not been broken during the insertion and that it remains in the tissues until its complete or nearly complete decay. It is advisable to combine in some cases the insertion of the emanation ampoules with powerful surface gamma ray radiations. In the introduction of the ampoules, the following technic suggested by Failla may be used : The glass emanation ampoules may be boiled and inserted into the shai'p end of a sterile needle which admits a plunger at the other end. It is convenient to have at hand a number of needles, each of which is loaded in this mainuM*. After insertion into the tumor tissue, the needle should be \vith(lraA\n a few millimeters just before the plunger ejects the am])oule so that the danger of breaking the am- poule by forcing it against the tissue is obviated. One may also withdraw the needle simultaneously Avitli the pushing in of the plunger. The ampoule thus rests in the miiuite cavity foi-med by the sharp end of the needle. I have devised a small instrument, which has been previously mentioned, for the insertion of the ampoules. (Fig. 36.) While theoretically some slight danger of inducing metastasis or trans- planting tumor cells may be incurred by tliis method, I am of the opinion that this danger is negligible if tlie technic is correct. The following suggestions may be observed in the insertion of the ampoules: — Aseptic precautions must be used; each ampoule should not contain more than three millieuries of emanation; the ampoules should be inserted about one cm. apart; cai-e should be taken not to implant them near large vessels, nerve trunks, bones or thin-walled viscera; if THE TECHNIC OF RADTATTON 157 possible to avoid it, tlic ampoules slioiild not be inserted into liealthy tissues. A zone of necrosis forms around eaeb ampoule a week or more after its insertion. Healing occurs in from four to eiglit Aveeks and in favorable cases a smooth cicatrix is left. The quantity or dose of radium emanation to be used in intratumoral radiation is considered in the Chapter on Dosage. It must be especially emphasized that the effects of radiation re- sulting from the introduction of radioactive substances into tumors are strictly localized. Tlie method is evidently not suited for the treatment of large, deeply situated lesions. Such lesions must usually be attacked by the method of deep gamma ray radiation that has already l)een de- scril)ed. In some cases, the two methods, intratumoral radiation and deep gamma radiation, may be advantageously combined. CHAPTER XV RADIU^I IN GENERAL SURGERY A. MALIGNANT TUMORS Careinomata exliibit different degrees of radiosensibility. Adler has tried to determine whether this difference in sensibility depends on the histologic striictnre of the tumor. According to this author's investiga- tions, rapidly grooving careinomata of the primary glandular type are almost refractory to radium while with the sclerotic types developing more slowly excellent results are frequently obtained. Bumm and Schaefer on the other hand have found that the so-called medullary car- einomata, in which the supporting stroma is scanty, are more easily influenced by radium than the sclerotic types. According to these authors no carcinoma has been observed that can resist radium. Kroenig and Friedrich also state they have found that every carcinoma can be influenced by radium if it is applied in the correct technical manner. They point out, however, that a difference in effect is to be observed in noncachectic and cachectic individuals. The former class of patients usually responds well, while in the latter class, heavy radiations may be ineffective or even dangerous. On this account these authors Avould exclude markedly cachectic individuals from treatment by radiations. In this view they are supported by Gudzent. Klein has shown that in the tissues surrounding carcinoma there is a so-called battle zone con- sisting histologically of advancing carcinoma cells opposed by leuco- cytes and connective tissue cells. In cachectic individuals, this zone is scarcely to be found, although the carcinoma may be advancing rapidly. From the clinical point of view, practically all observers agree that carcinoma in individuals who are in a relatively rol)ust condition is much more susceptilile to radiations than carcinoma occurring in the cachectic. We have seldom seen even good temporary results in those who exhibit considerable cachexia. Summing up the different views, we may conclude, in spite of some opinions to the contrary, that all accessible carcinoma is probably more susceptible to proper doses of radiation than most normal tissues. There is little doubt, however, that careinomata of different and even of the same pathologic types exhibit considerable variation in their response to ra- dium. Whether this depends altogether upon some difference in the radiosensibility of the tumor cells, it is impossible at present to decide. The writer believes that the radiosusceptibility of the growth is the most important factor. Other factors, hoAvever, in all probabilit}- are also at work in deteniiiiiiiig the response of the tumor to radiations. lo8 RADIUM IN GENERAL SURGERY 159 (a) Operable Malignant Tumors Janeway has raised the question of the advisability of treating pri- marily witli radium certain cases of cancer of the mucous membranes even though they may be operable. Gudzent states that it is justifiable to treat with radium selected cases of operable carcinoma provided the necessary surgical experience and an adequate knowledge of the technic of the application of radium can be combined. In cancer of the cervix uteri, even though it is operable, Bumm, Doederlein and Kroenig have abandoned operation in favor of radium therapy. Nearly all radium therapeutists are in accord, however, that with the exception of certain selected cases of epithelioma of the skin, and mucous membranes, oper- al^le growths sliould l)e operated upon. We have already mentioned that a certain type of malignant tumor in mice frequently cannot be successfully transplanted after radium treat- ment. The most rational procedure, therefore, even in dealing Avith clearly operable malignant disease is first to treat the growth and the lymphatics draining the involved area with radium. Immediately after- ward, operative removal of the tumor should be carried out. A few weeks later, postoperative prophylactic radiations should be given. (b) Inoperable Malignant Tumors In inoperable cases of malignant disease, treatment with radium has been followed in numerous cases by a clinical recovery that has some- times been maintained for a numl)er of years. Uadiuni, therefore, gives promise at least of a certain amount of relief even in those cases in which surgical procedures are inadvisable. It is of the utmost importance to bear in mind, however, that the inoperable cases submitted to radium fall into two categories: (1) Those in which it seems best to make a strong effort to bring about a clinical recovery. (2) Those in which only palliative treatment is advisable. Failure to recognize the latter class of cases will result in disappointment and even may cause great harm. Indeed, it is better to omit treatment altogether rather than to attempt the impossil)le and cause additional suffering from radium effects. The whole principle of the disappearance of carcinoma or other malig- nant growths under the influence of radium vays is based on the fact that the tumor cells are more susceptible to the rays than the normal tissues. According to many different authors, certain types of carcinoma ceils are four to seven times as sensitive as most normal cells. According to Friedrich and Kroenig's experiments with x-rays, the radiosensitiveness of breast carcinoma to the middle epidermal cellular layer is in the ratio of 170 to 150, i.e., 1.15 to 1. In other Avords, a dose of x-rays that will not destroy the epidermis will cause the resolution of breast carcinoma. Certain cases of squamous cell carcinoma are probably only 160 RADITTM THERAPY slightly more i-adiosensitivo than the middle epidermal layer. Radia- tion that falls short of destroying normal tissues "will often cause necrosis and disappearance of the tumor itself. One strives, therefore, to produce Avith radium a change in the growth th.it will not at the same time be accompanied by serious injury to the healthy tissue. This is best accom- plished by giving maximum doses at the outset. Subsequent doses should always be of less intensity. Some authors believe that a single intensive dose is best in dealing with malignant growths. This procedure seems to me, however, to be practical in only a few cases and sometimes is not without danger to the patient. Ordinarily, several intensive doses at suitable intervals are in my opinion to be preferred. In many inoperable cases that come under radium treatment, metas- tasis has already taken place. Tn such cases, palliation is all that can ordinarily he hoped for, although the primary groAvth can occasionally be healed by radium. We may now refer to the radium treatment of malignant disease oc- curring in different situations in the liody. THE TREATMENT OF CARCINOMATA For convenience of descrijition we may group together carcinomata affecting the different organs. 1. Epithelioma of the Skin The problem of ti-eatment of eiuthelioma of the skin depends to a great extent upon the type of growtli that is present. (a) Squamous-cell Epithelioma If the case is considered o]iei'al)le 1)\' the sui-geon and tlie adjacent glands are pal|);il)le. the di'aining lyin])]iati(' glands and growth may be excised "en hh)c." If the glands are not ])alpable, opei-ation may be limited to the gi'owth and I'adiation given to the glands. There is little doubt, howevei-, that cNcii in disliiiclly opci'able cases, ])reoi)(M'at ive radinin treatnu'iit will Itc of athantage. At the time of o]V'ration, emana- tion amjioules may be hiiricd in the opei-ation field. After operation. ])i-ophylactic i-adiations shoidd also ])e given. Over dosage should be guarded against. AVith an early diagnosis, reeoveiy should be brought about in at least 95 per cent of the cases. Inoperable cases of s(|uanutus-eell epithelionui may frequently be re- tarded in their progressv for considerable periods of time and in some instances a clinical recovery may be brought about. The diagnosis of squamous-cell from basal-edl epitliclioma is fref|uenl!y impossible with- out a microscopic seel ion and as it is often i?iad\'isal)le to obtain this a RADirAI IX GENERAL Sl^RGERY 161 few of the cliiiicjil points of diffevence may be iiulicatcd. (1) Its loca- tion. Ei)itlielioiiias of the lower lip, tono'uo, penis and extremities are usually of the s(iuamous-cell type. One-half of the epitheliomas of the upper lip are also of this type. (2) A papillomatous aspect to the growth is indicative usually of squamous-cell cancer. (3) TJapidly growing epi- theliomata with metastases to tlie adjacent lymphatic glands are prac- tically always of the squamous-cell type. It must he em])hasized. however, that there is no absolute rule holdiim- in all cases that allows of a complete clinical differentiation. The technic of the radium treatment of squamous-cell epithelioma of the glabrous skin when it is for any reason inoperable naturally varies with the clinical type. For very small and superficial growths ''one quarter" or "one half strength" glazed plaques may be used. Screened with 0.1 mm. of lead and applied in direct contact witli the skin, a total exposure of six or more hours may be given in several periods of one to two hours each. In dealing with larger, deeply infiltrated and ulcerated groAvths, it is best to use only gamma rays. In some cases two hundred millicuries, screened with two millimeters of bra^s and arranged so that it is con- centrated in the joroportion of 5 millicuries per square centimeter may be applied at a distance of 3 centimeters for thirty hours in periods of ten or more hours each. In six Aveeks, if there are evidences of the disease persisting, a similar course but of less intensity should be given provided signs of radium reaction are absent. Oreat care should be taken to avoid "burns" Avhieh may be very painful and prevent further treatment at a critical time. Some advise vigorous treatment with un- screened applicators for certain refractory types and even in ordinary cases. This procedui'e, howevei', causes consideral)le infiammatory re- action and if unsuccessful precludes for a time further ti-eatment in most cases on account of the pain. We prefer, therefore, the former method in oi-dinary cases ])ut in some cases we resort to the unscreened glazed applicators. In some cases bare emanation ampoules may be buried in the groAvth. For the prophylactic treatment of the ad.jacent lymphatic glands powerful deep radiations are advisable. Four hundred millicuries (5 mc. per square cm., 2 mm. screen, 6 cm. distance) may be ai)plied for a total of thirty hours. (b) Basal-cell Epitheliomata In the treatment of basal-cell epitheliomata, radium, in our judgment is the most satisfactory agent Ave possess and sometimes succeeds Avhen everything else fails. In spite of some statements to the contrary, Ave be- licA'c that this ty])e of epithelioma is one of the most amenable of all types of ncAV gi'owth to radium. Failure nmy, of course, occur in A^ery extensive cases in which the loss of tissue is very great and repair is 162 RADIUM THERAPY I'ig. 38. — Epithelioma of right cheek. RADIUM IN GENERAL SURGERY 163 Imk'. 39. I'aticnt in Fig. 38 after radium treatment. 164 RADIUM THERAPY Fig. 40. — Kpithelioina of right side of nose. RADIUM IX GENERAL SURGERY 165 Fig. 41.— Patient in Fig. -40 after radium trcalinent 166 RADIUM THERAPY Fig. 42. — Epithelioma of tip of nose. RADIUM IN GENERAL SURGERY 167 Fig. 43. — Patient in Fig. 42 after radium treatment. 168 RADIUM THERAPY Fig. 44. — Epithelioma of left lower eyelid. RADIUM IN GENERAL SURGERY 169 Fig. 45. — I'aticnt in Fig. 44 allu r r;Hliiim lir,i;iin.'nt. 170 KADIUM THERAPY Fig. -16. — KpitluliDiua of right inner canthus, eyelids and nose. RADIUM IN GENERAL SURGERY 171 Fig. 47.--l'aticiit in Imr. lo alter radium treatment. 172 RADIUM THERAPY l?ig. 48. — Epithelioma of kit inner canttuis, eyelids, nose, cliei_k an^l nppi r lip. RADIUM IN GENERAL SURGERY 173 l'"ig. 4'.'.- I'atiiiit in Fig. -48 after radium treatment. ]74 RADIUM THERAl'Y Fig. 50. — Eiiithelioiiia of tlie right tiinple. RADIUM IN GKXERAL SURGERY 175 Fig. 51. — PatifiU in I'lg. 50, after radium treatment. 176 RADIUM THERAPY Fig. 52. — r.pithelionia of the left temple. RADIUM IN GENERAL SURGERY 177 iMg. 53, — I'atinit in I'tg. 52 after radium treTtnieiit. 178- RADIUM THERAPY l.'ig. 54.— I'jiitlifliduui of Iflt malar region. Patient rt-lerred by Dv. Joscpli Scheurich. RADIITM IN GENERAL SURGERY 179 Fig. 55. — Patient in Fig. 54 after radium treatment. 180 RADIUM THERAPY Fig. 56. — Kpitlielionia of forehead. RAF^IUM IX GENERAL SURGERY 181 Fie. 57. — Patient in Fig. So after railuini ircatiiKnt. 182. RADIUM THERAPY Fig. 58. — Kpithelionia <0 after railiinn treal-iieiU. 186 RADIUM THERAPY Fig. 62. — Epithelioma of nose, left eyelid, cheek, and upper lip. RADIUM IX GKXKRAL STRGKRY 187 Fig. 63. — Patient in Fig. 62 after radium treatment. 188 RADIUM THERAPY almost impossible. In a few cases, there seems to l)e a lack of vital power in the cells to respond to treatment. Cases that have had various other kinds of treatment, such as exposures to x-rays, extending: over lonij- periods, frecpiently do hadly. The method of application in the l)asal-cell type of epithelioma is similar to that used, for squamous-cell cancer. Treatment of less intensity is usually sufficient, however. When dealini>' Avitli very small and sunerficial RADIUM IX GENERAL SURGERY 193 Pig, 67. — Patient in Fig. 66 after radium treatment. The insertion of false teeth gives the month a distorted appearance. 194 RADIUM THERAPY Fig. 68. — Epithelioma supervening on leukoplakia of right cheek. RADIUM IN GENERAL SURGERY 195 Fig. 69. — Patient in Fig. 68 after radium treatment. 196 RADIUM THERAPY I.-jg. 70.— Carcinoma of the tongue in patient apefl 65 years. Patient referred by Dr. E. P. rierg. Photograph taken July 7, 1921. KADIUM IN (JKNLJKAL SUKGKKY 197 \!\g ;i raticnt in iirivious figure aftrr insertion nf 1') niillicnrios of radium emanation con- incd ill 15 bare glass ampoules. Photograph taken July 15, 1921. Six months later patient appeared clinically well. 198 RADIUM THERAPY used consists in the application of 80 niillicnries concentrated in the ratio of 10 niillicnries per square centimeter. This may be screened Avith 1 millimeter of silver and 2 millimeters of rubber. A total exposure of eight hours in periods of one or two hours each may be given. We may now refer particularly to carcinoma of.- the tongue and car- cinoma of the tonsil. (a) Carcinoma of the Tongue Cancer of this structure is always of the squamous-cell type. It is the most likely of all cancers to invade the lymphatic glands early and widely. This in itself precludes successful treatment in many cases. In the most extensive cases, palliati(ui only can be hoped for. Sometimes cases seem to yield quite satisfactorily to the insertion of radium, con- tained in metal needles, into the growth. I have reported a case treated in 1917 in this manner, who is well at the time of writing. In this case, 60 milligrams Avere inserted into the growth for thirteen and one-half hours, and seven weeks later 72 milligrams for twelve hours. Hayward Pinch has buried approximately 21 to 53 millicuries, contained in a plat- inum needle, in certain nodules for twenty-four hours. Sharp reaction follows this treatment and in some cases the nodule becomes replaced with scar tissue. The method of using bare emanation ampoules has practically replaced the use of metal needles. In some cases, surface applications may be advantageonsly combined with the method of burying bare glass emanation ampoules. The greatest care must be used not to give an overdose and jirodnce sloughing. It must not be forgotten also that healing can only occui* when a bed of healthy tissue capable of i^roducing good granulations surrounds the growth. The regional lymph nodes may be treated in the manner already described. (b) Carcinoma of the Tonsil Cancer in this situation frecpiently yields to radium and sometimes displays a iiuii'ked susce])t ibility. If metastases t'l-oni a tonsillar growth are present in the neck these growths are also more than ordinarily sen- sitive to the rays. Jf the growth has extended to the tongue, the prog- nosis becomes the same as for cancer of that organ. We have successfully treated numerous cases of cancer of the tonsil. While formerly metal needles containing the radium were inserted in the growth, these have practically been given up in favor of the bare glass am- poules containing radium emanation. Kadium may be applied to the surface of the tonsil by means of a wire holding a specially con- structed piece of dental modelling compound adjusted to the area to be treated. Two hundred miMicuries screened willi the equivalent of 2 millimeters of bi-ass and 2 millimeters of rubber may be a])plied for three hours in periods of one hour each. The intensity of the treatment to be RADIUM IX GKNKRAL SURGERY 190 given naturally dcpetids upon tlio extent of the disease. If the growtli projects several in ill i meters above the level of the normal nuicous mem- brane, larger doses will be tolerated as the tumor tissue acts as a filter and in addition, the distance of the radium from the normal tissue is obviously increased. Instead of surface applications, several bai-e emana- tion ampoules may be buried in the growth. Five-tenths to 1 me. or more of emanation to each cubic centimeter of tissue may be used. In suitable cases, the combination of these two methods seems to be superior to either method used alone. Overdosage must be carefully avoided. (5) Carcinoma of the Superior Maxilla "AFany eases respond favorably to radium ti'eatmeiit. The disease most often begins at the alveolar process of the jaw. Carious teeth are usually found in these eases and the disease may apparently have started around one of them. The antrum is usually invaded early by the growth. ]\Ietas- tasis occurs relatively late in the disease. In the application of radium, the antrum, if involved, should be opened, usually above the alveolar process. Indeed in am^ case it is not wise to allow the antrum cavity to remain closed. By means of long silver Avires eai'rying the tubes, the radium may be brought into direct contact with the growth. In addition, heavy treatment may be given externally over the cheek and within the cavity of the mouth so as to radiate the growth from all sides. In the technic of treatment, much depends upon the situation and extent of the disease. Within the cavity of the antrum. 200 millicuries screened with 2 mm. of brass and 2 mm. of rubber may be applied for five hours. In the mouth, 200 mc. with the same screening may be used for tive hours. Externally, 250 mc, screened with 2 mm. of brass and ari-anged on a pad covering 50 sq. em., may be used for thirty-six hours at a distance of three centimeters in several periods of six to twelve hours each. G. B. New of the Mayo Clinic has used a eoml)ination of heat and radium in cancer of the jaw and cheeks. In cancer involving the antrum a solder- ing iron at a dull heat is carried into the antrum cavity and the growth is burned away. About two weeks later, when the slough has come away, radiiun is introduced into the anti'um cavity. (G) Carcinoma of the Inferior Maxilla and Floor of the Mouth Cancer of the lower jaw usiuilly begins on the alveolar process. Sooner or later, the floor of the mouth is involved and indeed it is frequently impossible to determine in just what structure the growth originated. In some cases, the floor of the mouth is the primary seat of the disease. As a rule, metastatic involvement of the lymphatic glands of the neck occurs early. On this account cancer of the floor of the mouth is much more malignant than cancer of the superior maxilla or cancer of the 200 RADIUM THERAPY Fig. 11. — Carcinoma of riglit siiiniK.r inaNilla involving antrum. Photograph taken January, 1915. RADIUM IX GKNKKAL SIHGEKY 201 Fig. 73.— Patient in Fig. 11 after radium treatment. Photograph taken April, 1913. 202 RADIUM THERAPY l)iioeal mucous nu'ml)rane. When metastases to the ueck are absent, radium treatment frequently produces a clinical retrogression and even complete healing of the growth. If the lymphatic glands of the neck are involved, retardation of the disease is all that can ordinarily be hoped for, although the primary growth may disappear under treatment. Two hundred millicuries screened with 1 millimeter of silver and 2 millimeters of rubber may be applied to the surface. A total exposure of four or more hours may be given. Instead of surface applications, several bare ampoules may then l)e buried in the lesion ; 0.5 me. to 1 mc. per cubic centimeter of tumor tissue may be used. The different areas of the neck likely to harbor metastases may receive prophylactic exposures. Five hundred millicuries screened with two millimeters of brass or its equivalent and concentrated on an applicator that has a superficial surface of 50 square centimeters may be used at a distance of 6 cen- timeters. A total exposure of twenty-five hours may be given in periods of ten or more hours each. If metastases are present, retardation of the growth may be brought about by the ordinary treatment for carcinoma- tous glands. (7) Carcinoma of Cervical Glands; Carcinoma of Thyroid Gland; Parotid Tumors For clinical convenience, carcinoma of the lymphatic glands of the neck, carcinoma of the thyroid gland, and tumors of the parotid gland may be considered together. (a^ Carcinoma of the Cervical Lymphatic Glands These cases are usually secondary to carcinoma elsewhere. The pri- mary focus is most frequently in the labial, buccal, pharyngeal, lingual or laryngeal mucous membrane. The supraclavicular glands are fre- quently involved in mammary cancer. The primarj- focus from which carcinoma of the lymph nodes originates may even escape detection altogether. In most of the mouth cases, the neighboring lymphatic glands sooner or later become involved although this event may be de- la3'ed for a considerable time. The treatment may be carried out by sur- face applications, by burying metal needles containing radium or radium emanation, or by buryiiig bare emanation ampoules. Sometimes a com- bination of these methods is most desiralile. Isolated and movable glands may be removed surgicall\- prior to radium ti-eatment. Following opera- tion, bare ampoules of radium emanation may be inserted in the operative field. If surface applications are used, 500 millicuries may be applied at a di.stance of 6 centimeters. Concentrated in the ratio of 5 to 10 millicuries per square centimeter and screened with tlie e<|uival('nt of 2 millimeters of brass, an exposure of twenty-five hours in several periods of ten or moi-c hours each may be given. If metal needles are inserted, 5 to 75 RADIUM IN GENKKATj SITRGERY 203 luillic'Ui'ic's ill steel needles that have a Avail Ihiekiiess of 0.4 nun. may be buried for twelve or ei«:lit hours. If bare emanation ampoules are buried in inoperable masses, a dose of 0.5 to 1 mc. or more ])er eubic centi- meter of tumor tissue may be given. Considerable judgment must be exer- cised in treating carcinomatous lymph glands. It must be remembered that the usual effect is retardation of the growth and that curative results can seldom be hoped foi'. Individual masses of glands that have some de- gree of mobility and arc not too large may sometimes be removed by radium. Masses of glands that are fixed, poorly nourished and of large extent can seldom be successfully treated. Doses powerful enough to cause death of the cancer cells may produce under these conditions sloughing of large ai'eas of normal tissue, which may add to the patient's discomfort and hasten his end. Douglas Quick has i-ecently described the iji-ocedni-e used at Ihe present time at the Memorial Hospital, New York, in dealing with cervical lymph nodes associated with intraoral cancer. In cases with no palpable nodes, surface radiations over the neck are employed, but excision of the lymphatic structures is not undertaken. In cases with palpable and operable nodes, surface radiations are fol- lowed by a neck dissection, preferably under local anesthesia. Following removal of the lymphatic structures, 5 to 15 mc. of radium emanation in bare glass ampoules are eml)edded in the operative field. Following this procedure, surface radiations may be used on the opposite side of the neck. Too much radiation over the affected side may devitalize the tissues. If it is found that the disease, at the time of operation, has perforated the gland capsule, radical surgical removal is deemed unwise and the mass is infiltrated with bare emanation ampoules, the wound being then closed. The statistics of this aulhor are encouraging. (b) Carcinoma of the Thyroid Gland Some cases of this disease are s1rikiiigl\' benefited. The teehnic of treatment should lie wliolly by external or surface radiations. Burying emanation needles in the«e tumors nuiy result in an intractable fungating growth. Powerful deep radiations must be used. Six hundred milli- curies screened with the ecpiivalent of 2 millimeters of brass and in the ratio of 5 to 10 millicurit^s ])er square centimeter may be applied at a distance of 6 centimeters. A total exposure of twenty hours in periods of ten or moi-e houi-s each may be given. Metastasis to the bones or other organs may take ])lace several years after apparent i-ecovery. (c) Parotid Tumors In carcinoma, endolhelioma, and certain mixed ])arotid tumors, en- couraging results have been obtained. In tumors containing cartilage not so much effect is to be anti<-iiKited. The teehnic may consist of the 204 RADIUM THERAPY application of 250 millicuries at a distaiie-e of 3 centimeters. Concen- trated in the ratio of 2.5 millicuries per square centimeter and screened with the equivalent of 2 millimeters of brass, a total exposure of thirty hours divided into periods of ten or fifteen hours each may be given. As in all other tumors, the teclinic varies witli the apparent depth of the growth and the area that it covers. It is not advisable to introduce radium or emanation needles into the parotid gland. Hayward Pinch has called attention to the ill effects that are likely to follow this procedure. A severe reaction followiiig the introduction of an emanation needle may result in the formation of a sinus which is kept open by the parotid secretion and from which an intractable ulceration may start. (8) Carcinoma of the Larynx In carcinoma of the upper larynx, or so-called extrinsic carcinoma, the results have been encouraging. In selected cases, one of the most effec- tive methods of radium application consists in the introduction of steel radium needles, each containing twelve milligrams of element or milli- curies of emanation directly into the growth. The needle introducer devised by Dr. 0. T. Freer is valuable for this procedure. The needles nuiy be left in the tissues for from eight to twelve hours. In one case of carcinoma of the epiglottis, base of the tongue and left vallecula, treated by the writer in conjunction with Dr. Freer, complete recovery occurred. In this instance there has been no local recurrence for over four years, but a recurrence in the glands of the neck two years ago yielded to ra- dium. The patient is now clinically well. This case has been previously reported by the writer. In iiiti-iiisic cai'ciuonia of the larynx, radiation from the outside or inside of the larynx may be emi)loyed. Kelly and Bnrnam have referred to several cases treated by extci-iial radiations that have recovered and remained well foi- vai-yiiig ])erio(ls. Ordinarily, however, the combination of internal and external treatment is necessary for success. It is doubt- ful whether extei-nal i-adiations alone are sufficient to cause complete regression. G. B. New of the ^layo Clinic has treated intrinsic carcinoma of the larynx in the followiiig inaiiiier: "Tracheotomy is first performed and after eoeainization the radium is dropped directly into the larynx. The radium is held in place for from one to one and one-half hours at a time. While all jiaticnts ;ifc not Ix'ncfitcd, \cry encoiii'aging results and remarkable relief have been obtained. One man had an extensive carcinoma of the larynx obsti-ucting the glottis so that it Avas necessary to do a tracheotomy; he Avas swaHowing (hiids only, in two months time he had gained foi'ty-eight ])oun(ls in Aveight and could eat anything. He had a cork in the tracheotonn- tube. The urowth did not recur RADIT'Ar TX GENERAL SURGERY 205 locally bill the ])atient died of eliest metastases a])out fourteen months later. However, the treatment ^-ave him a year of comfort." A method that promises to be even more effective than the one just described because it allows of accurate localization, consists in the appli- cation of the radium to the interior of the larynx by means of the special apparatus devised by Dr. 0. T. Freer. This apparatus is described in tlie eluipter devoted to a consideration of the use of radium in laryn- gologj^ Screened with 1 millimeter of silver, 200 millicuries contained in 4 or 5 tubes may be used, in periods of twenty or more minutes each for two hoiii's. During intralaryngeal treatments the throat must be kept free of saliva 1)y an electric suction pump. (9) Carcinoma of the Esophagus In this all but hopeless disease the results of radium ti'eatment in a number of cases have been encouraging. Among those who have reported their i-esults. some of Avliieh have been favorable, are Abbe, Exner, Kinhorn. l^'iu/i, ITayward Pinch, Janeway, Mills and Kimbrough and the writer. Abbe re])oi'ted a case alive and well nine years after treatment. Mills and Kimbrough have seen favorable results. In the cases reported by the two last-named authors, the coincident use of the x-rays enabled them to localize more accurately the position of the bougie carrying the radium in the esophagus. In one case, Finzi ob- tained a clinical recovery tliat had been maintained for three years when the case was repoi-ted. In another case a clinical recovery was main- tained for four years when the patient died suddenly. Postmortem there was found carcinomatous involvement of a small intercostal branch of the aorta with resulting hemorrhage. In one of the A\riter's cases, treated in conjunction with Dr. John A. (^avanaugh, apparent recovery was maintained for about one year wluMi the patient died suddenly of cerebrnl hemorrhage. Technic of Treatment of Carcinoma of Esophagus. — Previous to under- taking treatment, careful localization of the gi-owth is fill im])ortant. Skiagraphs with and Avithout a ])ismuth meal, direct esophagoscopy and measurements with bougies usually afford sufficient infornuition. It is necessary that the lumen ol" the growth admit a l)()ugie several milli- meters in diameter in order that the properly screened radium may pass completely Avithin the stricture. In some cases, sevei'al days ])i'ior to the treatment, a silk lln-ciid may be swallowed by the ])atieii1. The ])OUgie holding the radium may then be threaded upon the silk thread. This procedure will sometimes enable one in difficult cases to engage the apparatus in the lumen of the growth. The treatment may consist of the application of 100 to 150 mc, screened W'ith 1.5 mm. of silver. The bou- gie containing the radium emanation is passed into the strictured part of the esophagus and maintained in position for about eight hours. Prior 206 RADIUM THERAPY to the treatment morphine and atropine may be given hypodermically. A special attendant should maintain the bougie in place. Several treat- ments may be given at intervals of 3 or 4 days until the patient has received about 1500 mc. hours. Another technic adapted to certain cases and suggested by Janeway consists in the following procedure. A preliminary gastrostomy is per- formed. A silk thread is subsequently swallowed l)y the patient and the lower end is pulled out through the gastrostomy wound. A series of several radium tu])es is then attached to the oral eud of the string and pulled through the stenosed tract by means of the lower end. The upper tube is of such size that it will not slip through the strictured part of the esophagus but will rest upon the upper end of the carcinoma. Janeway has used several tubes, containing 30 or 35 mc. each, for from four to six hours. The immediate results of treatment are an improvement in swallowing due perhaps to the mechanical dilatation. About ten days later there may be increased dysphagia due to the onset of reaction. The hemor- rliage, odor and purulent discharge that may attend the passage and withdrawal of a bougie prior to treatment are no longer present. In a few weeks, as the reaction from the radium sul)sides, dysphagia is relieved and the patient may be able to swallow all kinds of food for a number of months. Greatly increased body weight and improvement in the general condition are usual accompaniments of the increased power of swallowing. (10) Carcinoma of the Stomach and Intestines In inoperable or recui-rent carcinoma of the stomach and intestines it is permissible to use radium in the hope of retarding the disease and relieving pain. Janeway lias seen improvement follow a combination of posterior gastroenterostomy and radium treatment. After the above o])eration was perfoi'iued, several radium tubes were i)u1led into place tlu-ough the gastrostomy Avound ])y means of a string previously swal- lowed. We have used a simihar method for carcinoma of the sigmoid flexure of the colon. Inguinal colostomy was first performed. By means of a string passed through the distal portion of the bowel from the open- ing in the colon to the anus a string of tubes was pulled backward through the anus until they engaged within the lumen of the affected portion. Technic of Treatment of Carcinoma of Stomach and Intestine. — Pal- liation is all that can be 1i()])(m1 foi- in these conditions. Symptomatic improvement has been noted following ])owei'ful. de(>p treatment to the abdominal Avail. The condition demands the use of at least 500 mc. This should be screened with 2 mm. of brass and placed at a distance of 6 to 10 cm. The concentration may be in the ratio of 5 mc. per square centi- RADIUM IX GENERAL SURGERY 207 meter. At a distance of G cm. an exposure of twenty-five hours and at a distance of 10 cm. an exposure of thirty-six hours may he given in periods of ten or more hours each. (11) Carcinoma of the Rectum Considerahle experience has heen accumuhited in the radium treatment of this disease. Rectal carcinoma varies a good deal in its response to radium. Adenocarcinoma of the annular, vascular type, situated in the upper half of the rectum, is probably more amenable than growths occu- pying only a portion of the rectal lumen and deeply infiltrating the rectal wall. Epidermoid Ciii-('iiioni;i in close proximity to tlie anal region is less easily influenced than llie otluM' types. A number of eases of complete regression of the growtli and apparent clinical cure persisting for vary- ing periods of time have been reported l)y different authors. The per- centage of clinical recoveries is not over 10 per cent. T1 must be remem- bered, however, that as a rule only cases in which surgical intervention is impossible are treated. Fully one-third of the cases are distinctly im- ]>roved. In borderline cases, radium treatment may render operation possil)]e. Technic of Treatment of Carcinoma of the Rectum. — The method of treatment and the dosage vary. Applications to the surface of the car- cinoma may be made 1)\' introducing the tubes attached to a long silver wire into the rectum. In other eases, bare emanation ampoules may be buried in the growth. These methods may also be combined. Carcinonui involving a segment of the rectal Avail is best adapted to the use of buried emanation ampoules. Carcinoma of the annular type may be treated by surface applications alone. In either condition, how- ever, the combined methods may be used. If tubes are inserted into Ihe rectum they may ordinarily be applied by means of a long pliable silver wire which is bent over the buttock to the proper angle and secured with adhesive tape. In the case of an annular growth, tlie tubes must l)e carried into the lumen of the growth. In using tubes in the treatment of growths occupying only a portion of the lumen of the bowel, a lead plate several millimeters thick may be used over the tubes on the side opposite the groAvth in order to protect relatively the normal mucosa. In other cases, the normal rectal wall ma}^ be packed off by means of a rul)ber finger cot, to which a catheter is attached. The cot is distended with air after its insertion. In some cases, the application of the radium is made best by the aid of the proc- toscope. The quantity of I'adium emploj'ed varies with different operat- ors. TIayward Pincli has used 50 me. screened with 2 mm. of lead and 2 mm. of rubber. An exposure of thirt}^ hours in periods of six hours each has been given. The course of treatment was repeated in six weeks if thought necessary. With the above dosage, proctitis will be slight or 208 RADITTM THERAPY absent. I favor, ordinarily, the nse of a miicli larger quantity of radium. Many cases may be treated with 200 mc. screened Avith 2 mm. of brass and 2 mm. of ru])ber for eight hours. The method of using even a larger quantity of radium for a relatively shorter time is preferable in many cases. If bare emanation ampoules are buried in the growth, the dose of 0.5 to 1 or more me. of emanation per cubic centimeter of tumor tissue is ad- visable. When radium treatment for carcinoma of the rectum is contem- plated, a preliminary inguinal colostomy is advisable in many cases, although it is not always absolutely essential. (12) Carcinoma, of the Penis, Vulva and Urethra Carcinoma of the glans penis sometimes responds favorably to radium. Certain cases may be very refractory. We have treated 3 cases in which clinical recovery has occurred. Tn these cases, amputation of the penis had been previously refused. Technic of Treatment of Carcinoma of Penis, Vulva and Urethra. — I have used in these cases either surface applications of radium or the in- sertion of bare emanation ampoules. Two hundred mc. screened with 2 mm. of brass may be applied at a distance of 1 cm. The concentration may be in the ratio of 10 mc. per sq. cm. An exposure of four or five hours may be given. Great care should be taken not to produce severe reactions which may be extremely painful in this situation. If radium emanation in glass ampoules is inserted, the technic previously described maj' be employed. Cancer of the vulva may be treated by burying bare emanation am- poules or by surface applications. These two methods may also be com- bined. T^nfortunately metastasis to the inguinal glands is usually an early complication of epithelioma of the vulva. The ultimate outcome is usually unfavorable although the local growth may be healed. Cancer of the female urethra nuiy ])e treated by the application of radium tubes to different parts of the growth or by burying bare emana- tion tubes in its substance. The tumor may be attacked from Avithin the urethi'a or from the external aspect. The groM'th may also be reached by radiations from tulics placed along tlit' antei'ior vaginal wall. Care must l)e taken not to oxcrexpose the urethral mucous membrane. As it is ijnpossible as a I'ule to introduce into the urethra a tube covered with sufficient rulihcr luhing to give an adctjuatc distance of the radium fi'om the growtli. a burn of the urethral mucous membrane may be easily caused without producing marked retrogression of the growth. One hundred mc. contained in two tubes arranged end to end, screened with 0.5 mm. of platiinim and 2 mm. of rubber may be introduced into the urethra for five houi's in several periods of one or two hours each. The external aspect of the growth may be treated in a manner similar to that suggested for epithelioma of the skin. The labia should be widely KADHAr IX gexi:rai> SruCKHY 209 separated with ina l)y means of a long silver wire which may be loent to the required angle and fastened with adhesive tape to the anterior abdominal wall. In some cases bare radium emanation tul)es may be buried in the growtli. The dose of 0.5 to 1 mc. per cubic centimeter of tumoi- tissue may be used. The different methods of treatment just de- scribed nuiy often be advantageously eond)ined. (13) Carcinoma of the Prostate Gland Benefit is fre([ue7itly to l)e noted from radium treatment of this con- dition. Fig. 74. — Adciiocpitlicliuma of the prostate. The Technic of Treatment of Carcinoma of the Prostate. — Formerlj- the radium coutaine^>. ■ . ■ • ' ■■■■•^ '■ ■ • •• •.ir*. • f. • •. ■'« • • • ... -••■4 .f^* . v-,'?VN : .^ f-.. — . •.•• ,]f/- '^■,: '<:^^\ /r\ ^>>-. '■=■■:.• ■ ^i ^::^::.-^>:<--- .:\::<-:<-^' %i^^^i:.^'-^'^^' Fig. 76. — Carcinoma of the breast after powerful radiation. Tlic entire section is shown. SHghtly enlarged {97 diameters). In this figure are seen, at B, glandular elements and the ex- cretory ducts, and, at C, the islets of neoplastic origin in the process of destruction. The can- cerous islets are situated at a greater distance from the source ot the rays than the normal glands, and yet the former exhibit greater effects from the radiation. The normal glandular elements remain unchanged, while the neoplasm is reduced _ to a state of degeneration. This illustrates the difference in resistance of healthy and neoplastic tissue. A, Epidermis reduced to several hyi)ertrophied cells. B, Normal glandular elements. C, Can- cerous islets in the process of degeneration. /?, Connective tissue stroma of neoplasm. D , Meta- plastic connective tissiie. uniting and taUing tlie place of destroyed parenchyma. 214 KADIUM THERAPY the patient absolutely refuses to undergo operation. Some of these cases may be successfully treated with radium when the local conditions are favorable. When the breast is not too large and the adipose tissue is not excessive and the tumor itself is small and well localized, success is pos- sible insofar as the local growth is concerned. Unfortunately, metas- tasis to the regional lymphatics or to distant organs precludes recovery in most cases. Fig. n . — Portion of Fig. 76 at B. Enlarged 800 diameters. A. Normal glandular cell. B, Supporting tissue. C, Lumen of excretory duct. D, Kiiithclial cell bordering upon an excretory duct. c A' B C Fig. 7.S. — rmUiiii oi I'ig. 7(1 at C, showing carcinomatous cells. Enlarged 800 diameters. The greater part of these cells are in process of degeneration although they have received less radia- tion than the cells in Fig. 41. A, IFypcrtrophied nucleus. B, Cell vi^ith pycnotic nucleus. CC , Atrophied cell with nucleus absent (Karyolysis). . D, Young fibroblast penetrating into a degenerated neoplastic islet. Inoperable Cases. — Tn cjises inopcmblc on account (if the extent of tlie disease, only pfillinl i\c Irciitnicnt jis a rule should be undertaken. In cases of the atrophic type, the progress of the disease may be retarded if the more accessible lymphatic glands alone have been invaded. In an inoperable case of this type recently under the writer's care, in which )iot RADIUM IN GENERAL SURGERY 215 only the whole hrcast Init the axillary and supraclavicular glands were involved, complete disappearance of all palpable masses was brought about by radium, but metastasis to the spine occurred. In the more rap- :^ ^ : :'---.:...:-:^s:rc])aralion which is taken from the center of a lobule. All these cells resemble one another. When lai'ge and deep tuiiKu- masses are present, radiations slioiild be of a penetrating character. Jii some cases, 400 millicuries, screened with 2 millimeters of brass and evenly disposed on a pad 9x12 cm., may be placed at a distance of 6 centimeters. A total exposure of thirty hours in periods of ten or nu)re hours each may be given. In otlier cases demanding deep effects, 600 millicuries, screened with 2 millimeters of brass may be placed at a distance of 10 centinu'tors and RADIUM LV GKXKRAI. Sl'RGERY 217 an exposure of thirly l,.,ur.s i.i i.cM-ie.ls of ton or more hours oaeli may be 8'iven. Sometimes wheu i)]eural or peritoueal effusion has supervened in consequenee of tiie involvement of the pleura or peritoneum by the growth, the fluid may he withdraM'n and deep radiation immediately p-iven. Tn some cases, the effusion has not reappeared. Dou-las Quick has recently reported upon the method of buryincr bare emanalK.n ampoules in the tumor in eases of inoperable breast "carei .£:''' ..-•v-'-y'^. M -••••■■ '•■■■■ .'.'■y'M'i' .-jy. ' :> -::''' ScctSfv'};c;;^f'^^oj'S:;;r's;\.^e:raf'!;,,th'^''^'' '■"'i^^'T- SHKh.ly enlarged ^97 dia.ncters). t!.o pareiiclivma nrV no ImiL, li ^ '• ,°^ "-^r.'"-. ^^' ''"'^^ '''^'^'' "^I'afi""- The elements of vaded ami HsWnted iVv vnm^^^^^ g'ouped, as in iMg. 79, ni lobular masses. These have become in- a.Ki L^len-zo^es J "''"" '"■°'"'''- ^ ''^ ^-pitheliomatous cells are degenerated embryonic elemems. '^-^'°'>'^'^^- ^''^ connective fssue stroma is renewed and is very rich in in n^w^^cenrl-epS^'he U,mor^e'rT!"T'""', -""f^ ''•^S^-ierated. BB, Young connective tissue rich disturbed, form^t^Z tl'JrS-n":^ ^.Llr^zt^^^'^e S S^o^s^""^"^^^ *'^^"^' "- 218 KADIUM THERAPY noma coincideiitly with surface applications of x-rays. Of seventy-eight cases treated in this manner by Quick, seven showed complete regressions for periods of three months to more than two years. Twenty-one cases showed partial regressions. Twenty-four cases received temporary ben- efit only. Ten cases showed no improvement and nine cases could not be traced. Seven cases were treated during the four months just prior to the report and were not included m the statistics, although the initial response to the treatment was favorable. Eussell Boggs has also re- ported favorable results from the insertion of steel needles containing Fig. 82 — A part of Fig. 81. Highly magnified (800 diameters). Note here the polyiiinriiliism of the tuinor elements, their hyi)ertropliic and malformed nuclear structures. The epithelinmatous nodules arc infiltrated with a vascular connective tissue development in a state of paracmbryoiiic metaplasia. Notice the presence, interspersed amongst the cpithcliomatous cells, of large, slar- shapcd anastomosing connective tissue cells. A, IIypertroi)hied epitlicliomatous cell with a giant nucleus. .)'./'. Cells with iiiultiple nuclei. B, Capillaries, newly formed at the edge of the infiltration. CC. I'seudoparasitic bodies. DD', I'ycnotic nuclei. E. Star-shaped connective tissue cell joined to its neighbors by protoplasmic elonga- tions. P, Young fibroblasts from the infiltration tissue. C, Mononuclear leucocytes interspersed in the infiltration tissue, l-f . Cell with vacuoles without nucleus in state of cvtolysis. //', Cell de- prived of its nucleus (karyolysis). radium salts into breast carcinomata combined Avith the use of surface radiations with x-rays. In the report of the London Radium Institute for 1919, ninety-five cases of cancer of the breast were mentioned that had applied for treatment during the year. Seven cases Avere examined but not treated: no recent RADIUM IN" GENERAL SURGERY 219 report had been received from 12 cases; 5 cases received prophylactic treatment; 50 cases were improved; 13 were not improved; 2 abandoned treatment ; 4 died and 2 were apparently cured. Between January, 1914, and January, 1921, the Avriter treated 90 cases F 5 cm Auner. Tig 83— Carcinoma of left breast. This tumor measured 16x12 cm., and was elevated about . above the level of the skin. Photograph taken October, 1919. Patient referred by Dr. A. J. of breast carcinoma of different types. Eighty-five of these eases were primarily inoperable or inoperable recurrences. Five cases were treated that Avere operable so far as the disease was concerned, but inoperable 220 RADIUM THERAl'Y Oil account of other conditions. In 30 of the 85 moperable cases just referred to, palliation only was attempted, the process being too far ad- vanced to permit of expectation of regression. Of the remaining 55 cases of this group, 6 showed complete clinical regression, 29 were definitely improved, 10 were not improved to a marked extent and 10 abandoned treatment. One of the earliest cases of clinical regression Fig. 84. — Patient in Fig. 83, showing improvenR-m umkr radiiiiu treatment. PhotoKiaph taken May, 1920. At tiiis time, the i)atient was free from macroscopic carcinoma. The open area at the site of the former growth was the size of a 25 cent piece hut was not carcinomatous. The small swelling at the junction of the arm and chest is merely a fold of skin. Complete heal- ing occurred later. Patient was livinpr and in good health one and one-half years after photograph was taken. Recently we have leanu. — Same epithelioma as in Fig. 8.S. Fragment removed 10 days after the first application of radium. (Enlarged 180 diameters.) /}, Cells that have not as yet undergone any changes. B, Cells influenced by the radiation and already showing signs of necrosis; (nucleus retracted in pycnosis — the chromatic substance scattered in the cytoplasm). C, Cells hypertrophied in varying degrees with irregular, often mon- strously hndileii, nuclei. RADITM TX GKNKRAL SURGERY 223 Inoperable Cases. — " Uterine caneer eoiitiiuies to yield most jjratifying results and the effect of radium treatment in inoperal)le eases is far in advance of those obtained by any other known medical or surgical meth- ods. " (Report of tlie London Radium Institute.) Certain authors are of the opinion tliat 25 per cent of inoperable uterine and vaoinal caneer can be cured by radium. The clinical improvement of the majority of cases of carcinoma of the cervix under radium is striking. Cessation of tlie liciiioi'i-liage and foul discharge and relief from pain are very frequently ol)tained. Disappear- ance of fungating masses and healing of ulceration are often noted. In D -^ - C - - -c Fig. 87. — Same epitliclionia as in l-'ip. 85. Section removed on the 29tli day after the first radia- tion. (Kniarged 180 diameters.) A, Group of hypertrophied epitheliomatous cells, degenerated, in process of disappearance (karyolysis, plasmolysis, cytolysis), imbedded in and infiltrated with: B, Embryonic and poly- niiclear cells. C, Remains of necrotic cells intermingled with polyniiclear cells which disorganize and absorb them. D, Young connective tissue rich in einliryonic cells, fibroblasts, plasma cells; the be- ginning of a cicatrization occupies the larger portion of the preparation. some cases, loalliation only is to lie expected. In a few cases, no improve- ment is obtained. The Technic of Treatment of Carcinoma of the Cervix. — The technic of treatment naturally \aries with dilTerent eases, and indeed almost every experienced worker with radium has, to some extent, an individual method. The difference in technic is quite remarkal)le and illustrates the toleration of the cervix uteri and adjacent tissues to radium treat- ment. It is noteworthy, however, that the enormous doses formerly rec- 224 RADIUM THERAPY ommended by some M-riters have been attended not infrequently by untoward sequelae and particularly by rectovaginal and vesicovaginal fistulae. The present tendency is toward moderate dosage in or against the cervix. A review of the different methods as practiced by Bumm, Cheron-Duval, Clark, Degrais, Janeway, Kelly and Burnam, Hayward Pinch, Schmitz. Wickham and many others, seems to demonstrate clearly that moderate dosage brings about tlu^ local disappearance of the cancer quite as well as enormous doses and without the untoward effects that may attend the use of very large quantities of radium. We believe also tliat severed ^^ '' *^fc^ - - B B A. -- \ A -I ... . -.<-:. -V,.3 • 1 -B •B pjg j cases: The total number of inoperable cases and inoper- able recurrent cases is 199, of Avhich 53 patients have been clinically cured, 109 markedly improved and 37 not improved. R Am I'M TX (5KNKRAI. ST'RGERY 227 "Our series includes 35 of oriiiiiuilly iuopci-ablc cjiueer of the cervix uteri or vagina in wliicli the patients are clinically cured, in 2 cases for over four years, in 2 cases for over three years, in 4 cases for over one year, and in 10 cases for over six months. Tt also includes 18 cases of originally iuopei-able i-ecurrent cancers in Avhich the patients are now clinically cured ; in 1 case for over six years, in 1 case for over four years, in 11 cases for over two years, in 10 cases for over one year and in 5 cases foi" over six months. Excluding' the operable cases, in which we liave both operated and used radium, there are 203 cases left; in 57 of these 203 cases the patients are 'clinically cured.' We will reserve the word cured for later reports, to apply to cases beyond the five yeai- limit, which has been conventionally adopted by surg-eons as a time limit for estimating the permanency of cures of malignant disease. Of the 57 clinical cures, 1 has lasted for six years, 3 for over four years, 4 for over three years, 5 for over two years, 20 for over one year, and 15 for over six months." F. J. Taussig has recently collected the available literature dealing with five year radium cures of cervical cancer. Out of 1114 cases, oper- able and inoperable, reported by twelve authors in different countries. 223 Avere said to be well after five years (about 20 per cent). Out of 415 operable cases, 131 were well after five years (about 31 per cent). Between January, 1913, and January, 1921, the writer treated 138 cases of carcinoma of the cervix. These cases may be divided into three groups. (a) Primary doubtfully operable, i.e., "borderline" — 10 cases. (b) Primary inoperable — 88 cases. (c) Inoperable recurrences after operation — 40 cases. Of the 10 borderline cases forming the first group, we have reports from 6. Three of these are living after more than three years and 3 are dead. Of the 88 primary inoperable eases forming the second group, reports have been obtained from 45. Twenty-eight of these are living and 17 are dead. Twehc of the living cases are well after more than three years. It may be stated, howevei', that in this group of inopei-able cases there were 12 in whom palliation alone was attempted. Of the 40 inoperable recurrences forming the thii'd gi-cuij), we have reports from 20. Of these 8 are living and 12 are dead. Of a total of 138 doubtfully or wholly inoi^erable cases, 51 have been lost sight of. Eighty-seven lia\(' been ti-aced, of whom 30 are living and 57 arc dead. If we assume that none of the uiit raced cases is liv- ing the pro])orti()n of clinical recoveries foi- moi-c than three yeai-s is slightly more than 21 pei- cent. In the majority of all of our cases, except those in which palliation oidy was attempted, local healing occurred under radium, and life was pro- longed and made bearable. 228 RADIUM THERAPY SARCOMATA When treated early and before dissemination to various parts of the body has occurred the results of radium treatment in sarcomata are on the whole beneficial. Unfortunately, the occurrence of metastasis may sooner or later render the prognosis unfavorable, but numerous cases have remained well for considerable periods of time. Different types of sarcomata exhibit marked variations in their radio- sensibility. Lymphosarcoma is particularly sensitive to treatment. It is one of the most gratifying of all growths in its response to radium. In this type of disease, large tumors which may affect the neck, medias- tinum, retroperitoneal h'mph glands, etc.; may disappear in the most surprising fashion. Fig. 89. — Polymorphous sarcoma with predominance of fusiform cells. Before radiation (en- larged 400 diameters). The chromoplasm of the cells is quite abundant, forming a mesh-like net- work filled with hyaloplasm, with no elaboration of the collagen. A, Fusiform cell. B, Vessel lying in sarcomatous tissue and bordered by tumor elements. C, Cells in atypic karyokinesis. D.E., Plasma cells. In a type of tumor usually referred to as sarcoma but classed by Jane- way and Ewing as "teratoid carcinoma of the testis and ovary" a remark- able susceptibility to radium is seen. Janeway has reported a number of cases successfully treated. In one of the writer's cases, referred by Dr. W. A. Stiihr, Avhich was probably of the type just mentioned, a large mass was present in the right hypochondrium. The tumor extended from the costal arch to the umbilicus and was apparently larger than a child's head. This growth had l)een preceded a year l)efore l)y a sarcoma of the right testis which had been surgically removed. Complete disappearance of the abdominal RADIUM IN GENERAL SURGERY 229 tiiinoi- oct'Ui-rcd witliiii a feAV weeks uiidei- radiimi trealmeiit. The patient is now in exeeilent health after more than tliree years. Melanosarconia is not, as a rule, favorably affected by radium but in exceptional cases may yield completely. AVe may refer briefly to sarcomata occurring in different situations. (1) Sarcoma of the skin is usually amenable to radium Ireatment. ?A »apir B l-'ig. 90.— Same sarcoma as in l-'ig. 89. Section of large nodule removed 15 days after powcrfur irradiations. Slightly enlarged (80 diameters). Zone A, Superficial part, in contact with the apparatus; zone of massive necrosis. n,.;f/hMl ' f !'°^''"S cellular monstrosities and phagocytes. Sarcomatous elements scanty but ciuite bulky and in state of degeneration. Numerous leucocytes. tronlfieH%n;,„=^n?'^'"n "'"'"'" °^ least modifications-nevertheless the sarcoma is modified. Ilvper- tropniea tonus ot cells of monstrous shapes. ' voun"^ fibroblasM? '^Tm'u^'^ f "'■ , ^''• '-'""g^t^^l sarcomatous elements having a resemblance to joung fibroblasts, cc, Multinucleated plasma cells. ;, Sarcomatous vessels. 230 RADIUM THERAPY (2) Periosteal sareoma is frequently benefited by radium. (3) Sarcomata of the tonsil and postnasal space are frequently amen- able to radium and very striking results are sometimes obtained. I have treated in conjunction with Dr. 0. T. P'reer three cases of sarcoma of the postnasal space in which recovery occurred. Two of these eases have remained well for more than three years. In one case, late glandular involvement proved fatal. (4) Sarcoma of the larynx may be treated in a similar manner to that suggested for carcinoma. # # Fig. 91. — Same sarcoma as in Fig. 89. After radiation. Highly magnified (400 diameters). This section shows a portion of zone B in Fig. 90 and illustrates the extraordinary volume, and the strange forms of the sarcoma elements under the influence of the radiation before they dis- appear by phagocytosis. The relative scarcity of neoplastic cells is plainly discernible. AA, (ireatly hypertrophicd sarcomatous cells with multiple or polylobular nuclei, with proto- plasm, acidophilous, invaded by polynuclear leucocytes. fiS, Neutrophile polynuclear leucocytes enclosed in the i)rotoplasni of the degenerated sarcomatous cells. C, Fibrillar stroma infiltrated with leucocytes. (5) Sarcoma of the orbital tissue recurring after operation is often benefited by radium. Unfortunately, metastasis to the neck or distant organs occurs sooner or later in most of the orbital cases. (6) Mediastinal sarcoma. Numerous instances of mediastinal tumor have received great benefit from radium treatment. It is probable that many mediastinal growtlis are lymphosarcomata and the excellent results sometimes noted nl'ter rjidinm Ireatment may be ('X])lained by tliis fact. l>urnam lias repoiled an interesting grou}) of 8 cases of mediastinal RADIUM IN GENERAL SURGERY 231 232 RADIUM THERAPY tumor treated with radium, in which the greatest improvement occurred in all ])ut 1 case. The Technic of the Treatment of Sarcoma. — The method of treatment varies greatly according to the situation and size of the tumor. In post- nasal cases, 100 mc, or more, screened with 1 mm. of silver plus 1 mm. of rubber may be used. Contained in two tubes placed end to end, the Vig 94. — Sarcoma of left check in girl aged nineteen. Photograph taken May 17, 1921. Patient referred by Dr. O. T. Roberg. radium may be applied through the anterior nares for six hours in sev- eral periods of two or thi-ee hours each. The treatments may be given every day or on alternate days. In tonsillar sarcoma, radium needles may be buried in the growth (60 mg. in 5 needles, 5io ^^- screen, 8 hours), or bare emanation tubes may preferably be used. In orbital sarcoma, 100 mc, screened Avith 2 mm. of brass may be inserted into the orbital cavity for six hours. Tliis treatment should follow evisceration RADIUM IX GKXKRAI. SURGERY 233 or exenteration either at the lime of the operation or in the event of recurrence. In all types of deep sarcoma or ^vhen large masses exist, deep rayino- Avitli large quantities of radium is the method to be chosen. Five hu^ndiTd or 1000 mc, to each 100 square centimeters, screened with 2 mm of brass and placed at a distance of six or ten centimeters may be applied. At a distance of 6 cm., 12,500 mc. hours and at a distanee of that patient's health was faihiig. 10 cm., 18,000 mc. hours may hv -iven. In mediastinal tumors, Kelly and Burnam have used more Ihan a -ram of radium at a distance of from V/> to 6 inches, for periods of four or more hours on each area. Panco'ast has reported some encouraging results following the radium treatment of brain tumors (sarcoma, glioma, emlolhclionui. i. Unitary tumors). 234 RADIUM THERAPY Fig. 96. — TumoiB c;l eyelids. .Microstoiiic SfCtiou .shuvvid lyin|iliciiii;i (?l. i'luUugi aph taken July, 1920. I'alicnt referred by Dr. Win. A. Fisher. RADIUM IN GENERAL SURGERY 235 iqg. 97._I>atient in Fig. 96 after radium treatment. Photograph taken September, 1920. Patient was well one and one-half years later. 236 RADIUM THERAPY Fig. yS.-Sarco.na of bone. Recurrence after operation. Patient referred by Dr. A. B. Kanavcl. RADIUM IN GENERAL SURGERY 237 Fig. 99. — Patient in Fig. 98 after radium treatment. Improvement was only temporary. >38 RADTUM THERAPY :■ 100.— Lymphosarcoma of ncrk. Photograi ,h taken July, 1919. Note scar of previotts operation. RADIT^^r TX GEXERAL SURGERY 239 y^^'^'^^^^-ren^^^^^^ . Photo.^raph taken in Decen,hor, 1919. 240 RADIUM THERAPY B. BENIGN TUMORS The treatment of keloids, nevi. ete.. Avill he considered in the chapter devoted to Kadiiim in Dermatology. The treatment of fibromyomata of the uterus M'ill be considered in the ehai^ter on Eadium in Gynecology. C. CHRONIC INFECTIONS Tuberculosis Tuberculosis of the skin will be considered under Eadium in Derma- tolopfy. Tuberculous Adenitis In the early stages of tuberculosis of the lymphatic g-lands, radium treatment frequently causes a diminution in size of the glands and some- times brings about a clinical recovery. Moderately deep radiations should be given. Two hundred millicuries distributed in the ratio of V/2 mc. per square cm. screened with 2 millimeters of brass and placed at a distance of 3 centimeters may be employed for thirty hours in peri- ods of ten or more hours each. Tuberculous Sinuses On numerous occasions we have introduced 25 to 50 milligrams con- tained in two or more tubes screened with one mm. of silver along the course of tuberculous sinuses leading to the bone. A total exposure of four to eight hours has been given. Improvement has sometimes fol- lowed. Other authors have reported the healing of such sinuses. In military surgery, Cameron has seen improvement follow the intro- duction of a radium tube containing 10 milligrams screened with one mil- limeter of silver into chronic sinuses for periods of ten to thirty minutes repeated several times at intervals of two to four days. Actinomycosis Actinomycosis has been treated with radium by Heyerdahl who has reported six cases. Four of these Avere clinically cured and tAvo were improved. CHAPTER XVI RADIUM IN GYNECOLOGY A. MALIGNANT TUMORS The treatment of carcinoma of the uterus, the labia, the urethra, etc., has already been coiisidored in the chapter on Radium in General Surgery. R. BENIGN TUMORS Fibromyoma of the Uterus Dr. Ro])ert Abbe, of New York, was the pioneer in the use of radium in filu'omyoma of tlie utei'us. His first case was treated in 1905 liy the introduction of radium into the interior of the uterus. In proper cases, radium treatment of uterine fibroids is now a routine procedure with those who have had experience with the method. Abbe, J. G. Clark, Deo-rais. Hayward Pinch, Kelly, Schmitz, Stacy, Wickham and many others have used radium extensively in this condition. Kelly has reported a series of 210 cases. Clark has observed more than 150 cases. I have treated over 60 cases. While there is general agreement as to the ben- eficial results of treatment, there are naturally some differences of opinion as to the class of cases in which radium is most suitable. With our pres- ent experience, we believe that one is justified in using radium in all cases of fibromyoma that are causing symptoms unless a positive contra- indication is present. Clark believes that fibroids in young women should be radiated with great caution on account of the possibility of bringing on an abrupt and serious menopause. He ordinarily limits the use of radium therefore to cases occurring within the menopausal cycle. Kelly apparently does not recognize an age limitation. Sixty-four of his cases Avere undei- forty and in twenty-eight of these, the tumor practically dis- appeared. The presence of acute or quiescent inflammatory conditions in the pelvis is a positive contraindication. Clark believes that Avhen the tumor is larger than a three months' pregnancy, operation is to be pre- ferred. Dr. L. J. Stacy of the Mayo Clinic also believes that very large fibroids should be operated on and draws attention to the possibility of mistaken diagnosis and of unrecognized carciiu)ma of the fnndus. Many authors do not regard the size of the tumor in itself as a conti-aindication to radium. The cervical, the submucoiTS and the pedunculated varieties of fibromyoma are not suitable for radium treatment. Fibroids under- going degeneration should not be treated with radium. The chief positive indication for radium trcatiuciit is utci'inc luunor- 'i42 RADIUM THERAPY rliage due to the fibromyoma. Radium may be used, however, when hemorrhage is absent. The results of treatment are, in most cases, the cessation of the menorrhagia and metrorrhagia and the production of amenorrhea ; the reduction of the size of the fibroid, which may in some instances disappear. In some cases, the menses may reappear even after as long a period as two years. The application of radium entails no operative mortality. If radium fails, operation can be resorted to if thought advisable. Technic of Treatment of Uterine Fibroids. — The technic of treatment naturally varies, depending upon the nature of the case and also upon the operator. Radium may be applied either by intrauterine applications, or externally by surface radiations over the abdomen when the size of the fibroid warrants the latter procedure. Good results may be obtained by moderate doses in the uterus. In cases in which radium is applied externally over the abdomen large doses are necessary. The intrauterine application of radium is to be preferred as a rule to its external applica- tion. Both procedures may be used coincidently in suitable cases. In some cases, when there is great objection to intrauterine application or when the pelvis is choked by the growth and intrauterine manipulation is impossible, radium may be introduced into the posterior fornix and at the same time powerful radiations may be used over the fundus uteri. The latter method has been used successfully by Hayward Pinch and others. External treatment alone may be successful. 1. Intrauterine Radiations. — By an intrauterine application of suffi- cient intensity the endometrium may be destroyed Init ovarian activity may be preserved. In this respect the intrauterine application of radium appears to possess features of advantage over treatment with x-rays, as the symptoms of the menopause are frequently slight when radium is used in this manner and may be pronounced after x-ray treatment. The amenorrhea that is produced should last if possible until the fibroid has practically disappeared as the tumor may begin to grow again if men- struation returns. If this latter event happens, the treatment may be repeated if thought advisable. The production of amenorrhea requires ordinarily an application to the interior of the uterus of from 1000 to 1500 millicurie hours. The quantity of radium used and, therefore, the length of the application vary with different operators. Dr. Howard Kelly has used 500 millicuries in the uterus for three hours. In the technic of the above author's treatment, the radium tube, screened to emit only gamma rays was screwed to the end of an ordinary uterine sound and introduced to the fundus uteri. The radium was allowed to remain not longer than one-half hour in one place, an average of six changes being made by turning once from right to left and then by with- drawing the sound one cm. at a time. Dr. J. G. Clark has used 50 milligrams enclosed in one or two tubes. An intrauterine exposure of from six to twenty-four hours has been RADirM IX GYNKCOLOGY 243 given by this autlior. the sliorter exposure being nsed in women under thirty-five and the longer, in women in the menopausal eyele. Haj^ward Pinch of the London Radium Institute has applied about 50 millicuries screened with 2 millimeters of lead to the posterior fornix or to the interior of the uterus. The same quantity was used simultane- ously over the fundus. "When the posterior fornix was the site of appli- cation, a total exposure of thirty to sixty hours was given in the course of five to ten days. The series of treatments Avas repeated in six to eight weeks. If the interior of the uterus was treated, an exposure of from twenty-four to thirty hours was given. My method consists frequently in the use of 100 millicuries properly distributed over the interior of the uterus. The screening is usually 2 millimeters of brass or its equivalent of another metal plus 2 millimeters of rubber. With or without gas anesthesia, the cervix is dilated and curettage is performed in order to exclude malignancy and remove any polypi. The cavity of the uterus may be swabbed lightly with a 5 per cent solution of iodine. The radium tube or series of tubes, arranged so as to radiate the uterine cavity homogeneously, is then introduced and allowed to remain for from ten to fifteen hours. -As a result of an intra- uterine treatment, there may be some nausea and vomiting and a feeling of depression in the ensuing twenty-four or forty-eight hours. There is usually no subsequent pain. Hemorrhage usually stops at once, but in some cases may. diminish gradually and may persist to a slight degree for several weeks. FolloAving the treatment there may be a yellowish leucorrhea but this usually ceases within six weeks. The menopausal symptoms naturally vary with the age of the patient. In younger patients they may occa- sionally be quite severe, but in those within or past the menopausal cycle, sequelae of this kind are slight or absent. 2. Surface Radiations. — By employing surface radiations over the ab- domen a result similar to that obtained by intrauterine applications may be produced. Surface radiations are adapted to very large tumors. Employing this method, Kelly has used 1000 millicuries at a dis- tance of 10 centimeters from the skin. The emanation was distrib- uted at various points over the abdominal tumor and a total exposure of twenty-four hours was given. A satisfactory result may be ob- tained by using 500 millicuries, screened with 2 millimeters of brass. Distributed on a pad so that there may be a concentration of 5 milli- curies per square centimeter, 500 millicuries may be applied to different areas at a distance of 6 centimeters from the skin for twenty-five hours over each area in periods of ten or more hours each. At a distance of 10 centimeters. 500 millicuries may be applied for thirty-six hours in several periods. The course of treatment should extend over one or two weeks and may be repeated in six or more weeks if thought desirable, 244 RADIUM THERAPY although smaller doses should invariably be given in subsequent treat- ments. C. METRITIS AND ENDOMETRITIS In chronic metritis and endometritis recovery may often be brought about by the intrauterine application of radium. Several tubes, arranged tandem and containing a total of 50 millicuries, screened with the equivalent of one millimeter of lead and one millimeter of rubber, may be applied for from eight to ten hours. The treatment may be repeated in six -weeks if necessary. Endometritis that has resisted all the ordinary measures and was formerly cnralile only by the removal of the uterus is sometimes completely relieved. D. METRORRHAGIA AND MENORRHAGIA NOT DUE TO CANCER OF FIBROID In metrorrhagia and menorrhagia due to causes other than cancer and fibroid, radium is sometimes of the greatest value. S. M. D, Clark has reported 50 cases of the above conditions benefited by radium. This author states that in "hemorrhage in young women" without definite etiology, in aggravated and intractable dysmenorrhea, and in "chronic metritis" witli bleeding, radium lias given promise of complete relief. E. MYOPATHIC HEMORRHAGE In myopathic bleeding from the uterus many authors have reported favorable results. In such cases, in which there is persistent uterine l)leeding at the menopause without gross demonstrable cause, radium is very efficient. One hundred millicuries screened with one millimeter of silver and two millimeters of rubber may be applied to the uterine cavity for ten hours. CHAPTER XVII RADIUJNI IX DERMATOLOGY AVe have already ret'erred to the fact that radium rays may produce either a "selective" or an ''inflammatory" reaction in the skin. By some Avriters, the "selective reaction," a process by which pathologic tissues are altered without visible inflammatory changes, is held to.be the more important. The ease, however, with which the actual destruc- tion of certain pathologic tissues can be produced leads us to place ra- dium in the front rank as a destructive agent. Within certain limits, radium is superior to the other common destructive agents used in der- matology, such as chemical caustics, the cautery, carbon dioxide snoAv or liquid air, electrolysis, etc. In actual dermatologic practice, one often combines the effect of the "selective" and the "inflammatory" reaction. The inflammatory reaction should be reduced to a minimum, however, and, if possible, avoided altogether in treating most dermatoses. Too free use of the inflammatory reaction, when the cosmetic appearance of the treated area is important, is undesirable on account of the possi- ble development, within the succeeding eight or ten months, of telangi- ectases. These are almost always the result of too large doses. Fortunately even a scar resulting from too strong doses of radium is almost always smooth, elastic and free from defects inherent in almost every other kind of destructive measure, except the telangiectasia men- tioned above. In favoral)le cases, the color of the previously irradiated skin area is almost like that of normal skin. A slight pigmentation may be present for a time, but this always disappears sooner or later. "From the histologic point of view, the action of radium on the integument, at least in therapeutic applications, can be shown to produce the same ef- fects whether the condition of the skin be normal or diseased. The ele- ments of the epidermis, whether physiologic or pathologic, are absorbed by degrees and disappear, while the overlying malpighian epithelium pei-sists. The cells of the vascular connective tissue, whether normal or modified by inflammation or a carcinomatous process, have an alternat- ing evolution. In the first stage, they return to the state of embryonic connective tissue cells ; in the second, they again arrive at maturity under the form of elongated fibroblasts, which are superimposed and fol- low the regular lines of stratification, again forming connective tissue bundles and elastic fibers." (Dominici and Barcat.) We may mention here the main groups of dermatoses in which radium offers a possibility of use: 245 246 RADIUM THERAPY A. Malignant tumors. B. Benign tumors. C. Chronic infections. D. Inflammatory and gi-anulomatous infiltrations of uncertain nature. E. Hypertrophies. F. Neuroses. G. Disorders of the appendages of the skin: (a) Sebaceous glands; (b) hair and hair follicles. A. MALIGNANT TUMORS The treatment of epithelioma, carcinoma, and sarcoma of the skin has already been referred to in the chapter on radium in general surgery. Among the other malignant growths of the skin which may be greatly benefited by radium are Paget 's disease, xeroderma pigmentosum, and mycosis fungoides. B. BENIGN TUMORS (a) Keloids Keloids and certain cicatricial bands are very favorably influenced by radium. In keloids of recent formation, especially when they occur in chil- c ^ ' -' " '•■,j1--' *- -.' ' '7-. .. vt ~ ^"^^^ Fig. lui.— Lican-icial kclm,!. IuHuwuik a luirn ul thu lace. J'.cfjrc radiatiuu. bhghtly en- larged. The connective tissue cells arc scanty and the elastic libers even more so. A, Horny layer. B, Thinned rete mucosum. C, Keloidal tissue with elements arranged parallel to the plane of the section., D, Capillaries surrounded by a zone of cells. E, Deeper portions of the keloidal fibroma arranged perpendicularly to the plane of the section. RADIUM IN DERMATOLOGY 247 (Iren, a very excellent result is frequently obtained. In some eases the skin may be quite normal in appearance after involution of the keloid. In other eases, the treated area may be too white or too red, or it may have a smooth, j>lazed appearance which, although differing- from normal skin, is not unsatisfactory when compared with the keloid itself. Usually the keloid is levelled and pain is completely relieved. Compared M'ith other methods of treatment, radium is easily the method of choice in the treatment of this condition. ----C Fig. 103. — Same keloid as in Fig. 102 after radiation. Highly magnified. C.reater development of the connective tissue cells; polymorphism of these cells; notable increase of clastic fibers. A, Epidermis directly above corium in a state of transformation. B, Snrfacc zone of the keloid transformed into yonng fibroma, rich in cells. C, Young fibroblasts forming a zone resem- bling a myomatous development. D, Deeper zone which lias undergone less advanced changes. In keloids mixed with scar tissue, the prognosis is not so favorable as more intensive treatment must be given. The Technic of Treatment of Keloids. — The technic of treatment of true keloids will vary greatly according to the age of the ])atient and the size and duration of the lesion. A tentative course of treatment may first be given. One-fourth or one-half strength varnish or glazed ap- plicators may be used. Screened with ^/o i"J»'- of lead and applied closely to the skin, a course of two to four hours in six periods may be 248 RADIUM THERAPY given. At a distance of 2 mm., the time may be doubled. In children one-half or one-fourth of this dose should be used. In keloids of con- siderable thickness, radium salts or emanation in tubes instead of varnish plaques may be used advantageously. One hundred millieuries of radium Fig. 104. — Keloid of right great toe. Photograph taken May, 1914. Patient referred by Dr. J. R. Buchbinder. Im'k. lO.S.- -I'aticnt in Fig. 104 after ladimn treatment. Photograph taken January, 1915. emanation having a. coneenti'ation of 5 millieuries per square centimeter, screened with 1 millimeter of lead and at a distance of 1 centimeter may be applied for eight or ten hours in periods of one or two hours each. The series of treatment may be repeated in al)()ut six weeks, but the sub- sequent course should be of less intensity. KADK .M L\ DKiniATOl.OGY 249 "Above all, the principle Avhieh governs the teehnic, and of whieh the operator must never lose sijjht, is the necessity for influeneinji' the keloids to the extreme depth of their base, and acting' on their peripheral prolonj^atious. which sometimes extend far beyond Ihcir \isil)le limits. The treatment of a keloid should oidy l)e considered complete when the tissues show an almost noi-nud elasticity on palpation, even at a depth. "It is ])ossible then, to make use of total radiations of <^i'eat powei-. composed largely of I>eta rays, and employ them in frecpiently repeated exposures of short duration; or of 'surjienetrant ' radiations of weak quantitative A'alue. allowinjii' them a sufficiently long action; or of the simultaneous application of several insti'uments aetin ^.n. ........ iiluu,(,wh ,.,i.'„ t Qtpr flip Only the lower portion of the keloid bad been treated when the photograph wa. taken. Later the rest of the tumor was removed with radium. Pig. 107. — Patient in Fig. 106 after radium treatment. 252 RADIUM THERAPY l-'ig. lUS. — Kclciiil 1)1 hack (jt ncL-k. Kccurrence after surgical removal. I'aticnt referred by Dr. Bayard Holmes. RADIFM IX DERMATOLOGY 253 Fig. 109. — Patient in Fig. 108 after radium treatment. 254 RADIUM THERAPY Fig. no.- 'Acne kcl.Mil" of back of neck. RADirM IX DI.iniATOLOGY 255 Fief. 111. — ^Patient in I'ig. 110 after radium treatment. 256 RADIUM THERAPY Fig. 112. — Keloid of face following a burn. Patient referred by Dr. T. R. Ilinchion. Photograph taken January, 1919. RAnIT'^r tx dkrt^iatology 257 FiK. 113. — Patient in Fig. 11 J after radiuiii treatment. I'liotograpli taken June, 1920. 258 RADIUM THERAPY (b) Angiomata and Lymphangiomata Aiigiomata and lymphangiomata, as a class, were most unsatisfactory to treat until the advent of radium. Many of the more modern methods, such as the injection of hoiling water or hydrogen peroxide, destruction by liquid air, 002 snow, electrolysis, etc., are more or less painful and on this account alone are unsatisfactory, particularly in the treatment of children. With these destructive methods, it is difficult or impossible. ^•.^•i^' - v\ ■;>'■ --^''^'-^ I'ig. 114. — Flat angioma of the hairy surface. Kefore radiation. Slightly enlarged (97 diameters). A, Ca))illaries of flat endothelium tilled with blood elements. B, Hairs, perpendicular section. C, Sebaceous glands. D, Sudoriparous glands. E, Corium rich in collagen, poor in cellular elements. F, JN'ormal epidermis. in extensive cases, to obtain uniformity of coloring of the affected areas. With radium, on the other hand, a fading rather than a destruction of the angioma can often be brought about. While a certain place is left for other methods, radium is our most satisfactory agent in dealing with most cases of angiomata and lymphangiomata. Not all cases respond equally well, but in favorable and selected cases a good cosmetic result may be anticipated. In considering the treatment of angiomata with radium from a clin- RADTUM IN DERMATOLOGY 259 ical staiidpoiiil, we may follow, in I lie main, the iiroupino' sugu'ested by Wickliam and Dograis. On the basis of treatment, these authors have divided vascular uevi into the following groups : 1. Flat, superficial angiomata, level with the skin. 2. Flat, deeply infiltrating angiomata, level Avith the skin. r "J^-i:-^ N. I"* 0^ /■ / -/->^ Fig. 115. — Same angioma as in Fig. 114, after treatment with radium by the method of "selective reaction," i.e., without visil)le macroscopic inflammation. Slightly enlarged (120 di- ameters). The epidermis is of normal thickness and freed from interpa[)illary encroachments. The derma is composed of connective tissue rich in cells of mature fil)rol)last type, which are arranged parallel to the epidermis. The connective tissue and elastic fibers have a uniformly regular arrange- ment, vessels are scanty, hairs and follicles have disappeared, only traces of sudoriparous glands. A, El>iderniis resting on basal tissue which is hardly recognizable. B, Zone below the epider- mis, where the cells are abundant and parallel to each other and to the epidermis. CC, Traces of sudoriparous glands. D, Star-shaped connective tissue cells which have not yet evolved into mature fibroblasts. o. Raised angiomata, usuall}- with hard and more or less sclerotic sur- face. 4. Raised angiomata, usually soft and sometimes pulsatile and erectile. 5. Deep, subcutaneous and submucous angiomatous tumors. The above groups include the more common types of angiomata. These 260 RADIUM THERAPY RADIUM- IN DERMATOLOGY 261 2G2 RADIUM THERAPY Fig. IJO. — Cavenimis angioma of lower li]). Patient referred by Dr. S. L. Fridus. RADICM IX DKiniATOr.OGY 2G3 Fig. 121. — I'aticnt in Fig. 120 after radium trcatinent. 264 RADIUM THERAPY l*'iK. 122. — Flat angioma of side of facr. iKik, ilim an'l I'lwri- RADITM IX DERMATOLOGY 265 Fig. 123. — Patient in Imj;. 1--' after radinni tveatinint. Tin- result in this case was 1)ettCT tlian in- dicated ))y tile ijhdtograpli. The angioma was remuvcd hy "selective reaction." 2()6 EADIUM THERAPY 'T ii i- t. KAniiriM IN DERMATOLOGY 267 ph sc; RADIUM THERAPY Fig. 128. -Slightly elevated angioma of side of face. Lesion was of dark, i)urplis!i-red color, ticnt refcrreil by l^r. 11. lulward Sauer. RADIUM IX DERMATOLOGY 269 Tlie result in this case is nnt pnod l,-j,r 1 'y — I'atiriU ill Imr. l-S after radium treatment. as indicated in the photograph as a few lelangiec.ases have appeared m the last year. 1 he.sc are easily concealed, however. 270 RADIUM THERAPY rig. 130. — AngiosaicDiiia (?) of left arm; note tumor of arm aiic Photograph taken April, 1916. aiiKinma of liack of arm. RADIUM IN DERMATOLOGY 271 Fig. 131.- — Patient in Fig. 130 after radium treatment. Note the disappearance of tumor and normal outline of arm. Method of dressing with strips of rubber tissue. A superficial derma- titis is also shown. I^hotograjjh taken June, 1916. Patient was well five years later. 272 RADIUM THERAPY ^^^HR^ ^- -.-* IVHp 1 V 1^^^'^^ % 1^ fc o ^'5 to — RADH'M IX DKRMATOLOGY 273 different types, liowever, merf^e into eaeli otliei- and different foi-ms may be present in the same person. The Technic of Treatment of Angiomata. — The method of treatment Avitli radium naturall\' varies ^\•ith the type. For most superficial anpfio- mata, nothing: equals tlie "toiles" or the o-jazed phujues. For deep angiomatous tumors, tul)es may he employed, altliouuli tlic^ flat ap]di- eators answer equally as well. 1. Flat Superficial Angiotxafa {"Port-irinc Shiins"). — In the treatment of this type of tumor, one eannot too stroiifily insist upon the necessity of the avoidance of inflammatory reaction. The in-oduction of slight redness and scalinu" of tlie skin is sometimes permissible, but an eiuleavor to bring about moi'(^ rapid r(>sul1s by stronu' treatment will oidy be fraught ■with disaster. Tf the dosage is too poA\erfnl or the tecluiic unshillful. the coloring may not be uniform and telangiectasia may occur. As an ex- ample of the technic, we may suggest the use of a Vjo strengtli "toile." With this style of applicator screened Avith ^/^(,o or Vf.o m^- (^'f aluminum and applied closely to the skin, an exposure of from two to four hours in periods of an hour each on successive or alternate days will suffice. In children, one-half of the above dose should be given. If a slight fading of the angioma occurs in six or seven weeks, sufficient will have been accomplished. Subsequent series of treatments should be of less inten- sity. With no class of cases is a refined and skillful technic more neces- sary in order to accomplish good results. Sometimes only a partial fading of the angioma can be brought about. 2. Flat, Deeply Infiltratincj Anqwrnaia. — Th? method of treatment of this type of angioma is similar to that em]iloyed in the first group, except that it is permissible to use stronger doses. Angiomata of the first group can sometimes be quite well concealed by the artifices of the toilet. An- giomata of the group that we are now considering are often so deeply colored and unsightly that no amount of artificial coloring or disguising really conceals them. We are justified, therefore, in proceeding some- M'hat more boldly. AVith the same apparatus and screen used in treating tumors of the first group, we may give an exposure of five hours in periods of an hour each on successive days. With one-fourth strength apparatus, screened with one-tenth millimeter of lead and applied closely to the skin we may give a total exposure of from three to four hours. At a distance of 2 millimeters, six or eight liours may be given. Only a few square centimeters should be treated at one time until the etfect is ob- served. Sevei-e reactions sliould be avoided. In sul)se(pient courses of treat- ment, instituted after six weeks or two months have elapsed, the screening may be increased to -/,(, mm. of lead and a total exposure of five or six hours in several periods of one or two hours each may be given. It is difficult to obtain good results in this gronji. but in some cases the final aj^pearance is excellent. 274 RADTT'M THERAPY 3. Raised ''Hard" Angiomaia. — Tliis group comprises a considerable number of clinical types with no exact limitations. The size and extent of the tumors vary greatly. In some, the surface may be smooth; in others papillated and irregular. A varying degree of hardness is noted on palpation, some being quite sclerotic. In this group, one is justified in producing definite reaction. AVith Y^ strength applicators, applied closely to the skin, a total exposure of two hours when unscreened, or five hours when screened with ^Xo n"^^^- of lead may be given as a first course. Screened with ^^o n^m. of lead plus 2 mm. of rubl^er, ten hours may be given. Not over 4 square em. should ])e treated at one time. The treatment should be divided into several periods of one liour eacli. When tlu^ reaction sulisides. a less intensive course with double the thickness of screen may be given. 4. Bailed, "Soft" Angiomaia. — In this group are included variously sized tumors. A frequent type is the "cavernous angioma," seen partic- ularly in infants. This tumor is elevated one or more centimeters above the skin level, and is frequently limited to an area of several square centimeters. In more extensive cases, the entire side of the head may be involved so that there is great deformity. It is in this group that radium is particularly satisfactory in its elTects. One should endeavor to utilize to the fullest extent the selective action of radium. Success frequently attends doses that produce little or no inflammatory reaction. The ''cross fire" method suggested by Wickham, in which the raised tumor is attacked from different sides, is especially useful. With one-quarter strength applicators, screened with one-tenth millimeter of lead and applied closely to the skin, an exposure of three or four hours in several periods may be given on one area. At a distance of 2 millimeters, eight hours maj' be given. As in the previous instances, not over 4 square em. should be treated until the effect is observed. The course may be repeated in six or eight weeks. In the case of very extensive tumors in infants, an exposure of two hours when the applicator is closely applied may be sufficient for the first course of treatment. Subsequent courses should be of less intensity. 5. Deep, Siihenianeoiis and Siihtnucous Tumors. — Very extensive tumors may be treated successfully. In these cases the deep penetrating method should be used. It is best to treat separate sections of the tumor succes- sively so as not to give an overdosage. Tubes may be used in this type of tumor, although plaques are more satisfactory. One hundred and fifty 7iiilli('iiries of radium emanation, having a concentration of 5 millicuries per s(|uare centimeter, screened with 2 millimeters of brass and placed at a distance of tw() centimeters, may be used on an area of about 30 square centimeters for ten hours in several periods of two or three hours each. Full-strengtli i-adium i)la(|nes may be used in a similar manner. The "cross fire" method should be utilized to the utmost in order to spare the skin. At intervals of six or eight weeks, subsequent courses of less intensity may be needed, altliougli two, or at most three, courses are RADIUM IX DF.R^IATOLOGY 275 c S ~ o 276 RADIUM THERAPY I'ig. 136. — rignientfd lu-vus of left lower eyelid ai RAHICM IX DKK.MATOLOGY 277 l'"ig. 137. — Patient in Fig. 1 g. 1j() atlrr ra' 278 RADIUM THERAPY RADIUM IX DERMATOLOGY 279 ^ B j= c o 280 RADIUM THERAPY usually sufficient. Oftentimes, large angiomatous tumors may be made to disappear without inflammatory reaction, the overlying skin being scarcely or not at all affected unfavorably. The writer has treated with Fig. 142. — Tuljerculnsis verruco.sa cutis of lir.st plialanx of left middle finger. V\g. 143. — Patient in Fig. 142 after radiinn treatment. radium more than tliroe huniliftl nngiomata of various types. In some cases, the i-esults have ])een excellent. In a few cases, there has been im noteworthy improvement. RADII M IN DERMATOLOGY 281 The Technic of Treatment of Lymphangiomata. — These rare tumors yield in excellent fashion to radium. Abbe reported upon the treatment of the first cases in 1915 and a few months later I reported an extensive ease involving the buttock and thigh that had been successfully treated. In lymphangiomata affecting tlie mucous membranes and particularlv Fig. 144. — Tuberculosis verrucosa cutis of first phalanx of left thumb. iMg. 145. — Patient in Fig. 144 after radium treainicnt. the tongue, radium is of uni(|ue value and can hardly be replaced by any other agent. The method of treatment is similar to that for angiomata of the third group. (c) Nevus Piginentosus Pigmented nevi iuvohing an area of several square centimeters are amenable to radium. \evy jiiinute nevi should be treated by other meth- 'JS2 RADIUM THERAPY ods. Growths that are very unsightly in consequence of rugosities and great thickening, the presence of hair, and very dark pigment, are espe- cially likely to yield to treatment. Kadium has unfortunately no selec- tive action on j^igmented nevi and in order to cause them to disappear destructive doses must be used. The final result therefore may not be as good as in angiomata, due to the fact that the treated area may be I'ig. 1-16. — Lui'ua \ iilgaris of riKht check in girl aged 13. uiic\cn]y (MiloiH'd and there may be points of repigmentation. We do not Hicrcfdrr I'ccuimni'iKJ tlic use of i-adium in faintly pigmented nevi. The Technic of Treatment of Pigmented Nevi. — Great care should be used in the treatment in order not to give excessive doses. With one- (|uarter strength applicators, api)lied closely, an exposui'e of one or two hours may be given without screening. Following this, an exposure of two hours with a screen of jjo niilliineter of lead may be given. This RAl)ir>[ l.\ l)i;irMAT()I,OGY >83 procodiii-c ])r()(lu('('s a sliolilly drsl i-iicl ivc ad ion. 'J'lic t real iiu'iil may be repeated, l)iit with less iiiteiisitx . in eight weeks. Tlie final rcsidl Mill depend veiy largely U])on the judieious seleetion of eases and ])('i-liai)s most of all, as in oilier eosmelie difficulties, npon the skill and care Avith "wliieh the treatment is carried out. "Fordyee's disease" of the miieons nuMubrane of the cheek and lii)s Fig. 147. — I'aticiit in Fig. 146 after radium treatment. has been treated snccessfully by ilaywai'd riiicli, myself ami olln'r writ- ers. A glazed phuiue of ^/4 strengtli, unscreened, may be used and a sharp reaction may be produced. An exposure of forty-five to sixty niiiuitcs may be given and repeated, if necessary, in a few weeks. In various olher benign 1inii(»i-s of Ihe skin, radinm has been fonnd to be of value. Among these may be mentioned esi)ecially limnir nevus, in which radium is of the greatest value. Dermatitis papillaris eapillitii, molluscum 284 KADIUM THERAPY Fig. 148. — I.upLis vulgaris of ri),'lit iluck. contagiosuni, multiple benign cystic epithelioma and some types of xan- thoma are also susceptible to radium. ( . CHRONIC INFECTIONS (a J Tuberculosis In certain types of skin tuberculosis, radium is of value Tuberculosis verrucosa cutis frequenth^ responds well. Destructive doses, such as may RADII'M INT ni'.KMATOI.OGY 285 Fig-. 149. — Patiiiil in Fig. 1-lS after radium treatnient. l)e o])laiii(Hl l)y using- Y^ strenglli applieators ^vitll a screen of Vio mm. of lead for five or six liours in several periods of one to two hours each, may be used. lu lupus vulgaris, radium is only of limited use, being, in the writer's judgment, distinctly inferior to the Finsen light. In using radium, the best plan of procedure consists in using % or % strength glazed appli- cators witli a Yiit mm. lead screen. A total exposure of six to twelve hours may be given in divided doses. Only small lesions should ordinarilj' be 286 RADIUM THERAPY treated. Large lupus patelies may even spread at the border and become worse under radium treatment if insufficient doses or unskillful technic are used. It is the general experience that radium has practically no selective action on lupus tissue. In lupus vulgaris of the mucous mem- branes, radium often has a very beneficial effect. Doses of less intensity than those used for the skin should be employed. (b) Blastomycosis In 1918. the Avritc'i- reported the results of the radium treatment of blas- tomycosis of the eyelid. Since that time, several other cases of Idastomy- cosis of th(> skill have been treated sncecssfullv. Radiation similar to that Fig. 150. — lilastoiuycosis of left iniur catitluis Fit;- 151. — Tutitiit in Fig. 150 after radium treatment. used for tuberculosis, but of less intensity is efficient. Degrais, Wickham and others have found local radium treatment of value in aiding resolu- tion of syphilitic skin ('ni|)t ions. The technic is simihir to that described above as suitable in tulx'i'culosis. I\adium has been used successfully by Kalilcr. (Juttinan and others in rhinoseleroma and bv Heverdahl in actinomvcosis. 1). INFLAMMATORY AND GRANULOMATOUS INFILTRATIONS OF UNCERTAIN NATURE In this groii]) of (Icrinal OSes, radiuin is of consith'rable value. In psoi'iasis, lichen ])laniis. lichen chronicns simplex, clironii! eczema and RAPir.M TX DERMATOLOGY 287 Fig. 152. — Luims trytheuiatosus ui iiusc and Lhctks. Fig. 153. — Patient in Fig. 152 after radium treatment. Photograph taken two months after treatment. 288 RADIT'M THERAPY lupus erythematosus, i-cidium treatment offers, in selected eases, a great amount of relief. In psoriasis of the nails, radium is particularly useful. In obstinate patches of psoriasis that do not yield to ordinary measures radium may he used successfully. It must be remembered, however, that neither radium nor anj^ other measure prevents recurrence of the patches. With Fig. 154. — Luinis erythematosus involving nose and cheeks. y^ strength applicatcu's, screeiuMl with |io i»»i- of lead, an exposure of one or two hours and often less, in several periods, is usually sufficient to cause involution. Inflammatory reaction sliould be avoided. In liclien planus confined to small areas radium often relieves the iteliing ami hastens invoUil ion. In lichen planns of the mucous mem- branes, radium is especially vahiahle. The technic of treatment is the same as that suggt^sted foi- i)s(>jMasis. Not more than ^^ of the dose em- jjloyccl oil tlie skill sliduld l>r used on lesions of the mucous iii('in])ranes. RADir.M IN' DI.RMATOI.OGY 289 In lichen clirojiiciis siinplcx, i-;uliuin oflt'ii t:i\('s tlu' most striking relief, the itcliiiio; fre(|ueiitly (lisai)i)(';ii-inj>- very i)i'onii)tly. Short appli- cations of '/4 to % sti'(Mi<>tli <»laz('(l ap])lic'ators, uiisi-recned, are advisable. Two or three ex])osui'es, cacli lasting' three iiiimites, and repeated at iiitei-vals of a week, ai-e etfieieiit. hiHaimualoi-y i-caction sliouhl be avoided. Certain cases of chronic eezenia may 3'ield lo similar treatment. The writer has treated more than ~}0 cases of Inpus erytliematosus I'ig. 155. — I'atifiit in Fig. 154 after radium treatment. ■\vith radium. In this curious and ])u/.zliiig disease, radium is one of our most valuable agents. Considerable judgment is necessary in treat- ing tliis disorder, aiul caution should be practiced until the degree of iri-ital)ility of tlie individual ease is made evident. j\[ost cases rerpiire only a moderate reaction to produce evolution. Treatment may be car- i-ied out ])y employing |4 i^trength gla/.ed ap])lieatoi-s. screened with lio mm. of lead. One-lialf hour ex])osures may lie given on successive or alternate da\s iiiilil four or five treatments have been given. The 290 RADIUM THERAPY Fig. ISr,. — I, 111. US trytlicnialusiis iiivulving riglit cheek and uiiper lip. RADIUM IN DERMATOLOGY 291 Fig. 157. — Patient in I'ig. 156 after radium treatment. 292 RADIUM THERAPY Fig. 158. — Lupus erythematosus of four years' (Juration. KADI 1 1. M IX DKKMATOLOGV 293 I'ig. 159. — Patient in Vig. 158 ati i , i liivnhni,! ui.is show tlie scarring of the disease anil are ni a lighler culm- than the ncirnial sliin. 294 RADIUM THERAPY effect is noted and the treatment is repeated as soon as the reaction, whicli may last for f i-om two to four Aveeks, has subsided. Care must he taken tliat the ed«>'e of tlie applicator overlaps for at least five to ten millimeters, the visible ('d<:e of tlie disease. This treatment is usually adapted only to the cases of "fixed type." Freedom from the disease for several years may be experienced iu certain cases. In other cases, a relapse may occur in a few months, or even sooner. In some cases of lupus erythematosus, little benefit is derived fi'om the treatment. In leukemia cutis, radium is of value ami may cause resolution of the involved areas. E. HYPERTROPHIES In many of the disorders classed as hypertrophies, radium is of con- siderable value. In clayus, callositas, and the various keratoses, such as keratosis senilis, x-ray keratosis, angiokeratoma, etc., radium is of value. The general method of treatment of these disorders consists in the use of y^ strength apparatus, unscreened, for one-half to two hours, or screened with Y^^ mm. of lead for three to four hours. Warts and Papillomata Although often regarded as trivial, the subungual and periungual wart, and the palmar and plantar wart deserve special mention because they are peculiarly resistant to the ordinary dermatologic measures. The ])lantar wart may cause great distress and pain on walking. As a rule, all these growths yield easily to radium treatment. One-fourth strength glazed apparatus unscreened applied carefully for from one-half to two hours is usually sufficient to cause involution. A still better method in some cases, because the reaction produced is negligible, consists in using the same appai-atus, screened with Yn^ mm. of lead, for four hours in jieriods of one honi' each. In certain rare disorders, such as acanthosis nigricans and Dariei-'s disease, radium treatment would undoubtedly be of value insofMi- as the i-emoval of localized areas of the disorder is coni'ci'iicd. I\. L. Sullon luis used radium sncccsst'nlly in a "synovial lesion" of 1 lie skin. F. NEUROSES OF THE SKIN AVe lia\(' ali'cady si)oken of the i-elief obtaiiu'd l)y the use of radium in certaiii itcliiiig dernmtoses, notably lichen chronicus simplex, lichen ])lanus, and eczema. There are other disordei-s classed as neuroses in which the suh.jccl i\-c sym])toms are ])rominent, but i)i \vliicli little or nothing is seen olijcct ixcly except the lesions ])roduced by scratching. Localized pruritus, sucli as ])ruritus ani and ])ruritus vulvae, is fre- quently relieved by radiniii. In Ihese a (Ted ions, the best method of treatment is by means of unsereened glazed apparatus. Exposures of KADir.M IX DKK.MATOLOGY 295 three to five niiiiuU's' diii-atioii re])('ated several linics at intervals of a "week, may be i>-iveii. The lolal aiiioimt of i-adiatioii slioiild never be sufficient to produce an iidlainniatoi'v reaction. In \ari<>us other affec- tions, tlie analgesic action of i-adiuni has been made use of. Tn hyper- estliesia, following- herpes zoster, in neuritis and in intercostal and sci- atic neuralgia, Wickham found radium of value. ][e used approximately Yi strength apparatus screened with Yn) mm. of aluminum and gave applications of from ten to fifty minutes. Reaction in the skin should be avoided in this class of cases. G. DISORDERS OF THE APPENDAGES OF THE SKIN (a) The Sebaceous and Sweat Glands In selected cases of acne rosacea radium is of value. In rliinophyma very good results have been obtained by AVickham and Degrais and oth- ers. In these cases, Yi strengtli glazed applicators, screened with Yio nim. of lead, are usually employed and a slight reaction may be produced. A total exposure of two or three hours in several periods Avill usually be sufficient. Subsequent courses may be given at intervals of three to six weeks. (Jood results may follow the local ti'eatment of acne varioli- formis although, of course, no influence is exerted in preventing the for- mation of new lesions. In hypcridrosis, radium is sonu'times of value. The glazed ])la(|ues are the nuist convenient form of apparatus. Intlam- matoiy reaction should never be produced. (])) Hair and Hair Follicles In the extrcnn^ cases of hyi)ertrichosis whicdi may cause so much men- tal anguish as to wreck the happiness of the individual, radium may occasionally be employed. Sometimes, however, in order to ])roduce per- manent alo])ecia a degree of atrophy must be produced that is undesir- able. Telangiectasia may also be caused. In selected cases, however, we have obtained very excellent results. In hypertrichosis, the following technic may be used. All areas that are not to be alfected must be cov- ered by at least 5 mm. of i-ub))er covered lead. One hundred fifty mc, screened Avith 2 mm. of biass, may be arranged on a wooden pad 6x8x2 cm. At a distance of 2 cm., wliich is the thickness of the Avooden pad. an ex])osure of thirty houi's in two [jcriods may be given. In cases in wliich 1em|)orai'y alopecia is desii'cd. as in ringwoi-m and sycosis vulgaris, ra- dium may be used instead of x-i'ays. though often inferior in convenience to the latter agent, ixadiuiii is perhaps safer in inex])ert hands. In extensive ringworm of the scalp, we have used tlu^ following technic. Blocks of soft wood or cork (2x2x1 cm.) may be arranged to form an applicator having a sui)erficial area of 100 square centimeters. Radium em- 296 RADIUM THERAPY Fig. li>lJ. — Sycosis vulgaris. Fig. 161. — Patient in Fig. 160 after removal of hair with raiiiuni. anation tubes may be arran<:;e(l on this applicator in tlie ratio of L25 inc. per square centimeter. Screened -with one millimeter of silver and at a distance of one centimeter, an exposure of forty-five hours may be given in three jieriods of fifteen hours each. Temporai-y alopecia results. CIIAPTEk XVIII RADIT^^r tx oi>irniALMOLO0Y, otolociy, riiixology and LARYNGOLOGY OPHTHALMOLOGY A. Malignant Tumors Epithelioma of the Eyelid lias ])('vn i-efcircd to in llio cliaptor on Txadiiuii ill 1 )('nna1(il(ioy. Epithelioma of the Conjunctiva has Ix'cii successfully Iroalcd by Wiek- liam and DejiTais aiul otluu-s. Sarcoma of the Orbit lias Ixmmi considei'cd in tlic cliii])1 cr on TJadium in Geiu'ral Sui'. Vernal Conjunctivitis 111 vernal conjuiU'tivitis radium is of coiisidci-ablc \alue. Soincl imcs the most rebellious cases are eomiiletely relieved. Treatment should be carried out cautiously. A "full streng'tli" applicator unscreened may be employed and a fifteen miiuite exposure given. In two weeks the exposure may be repeated, but only if inflammatory reaction has beeii slight or absent. Instead of the above type of applicator radioactive deposit may be collected on lead foil and used in a similar manner. Abbe, Allport, Butler, Davidson and Lawson, Schnaudigel, Shine, Shum- Avay, and many others have reported successful results. 0. Trachoma Radium is often of benefit in lliis intractable condition. The lechnic is similar to that suggested for vernal conjunctivitis. D. Cataract Cohen and Levin have rei)oi-1 cd upon the use of radium in twenty-four cases of imnuiture cataract and claim iini)roveiiien1 in ST. 5 jier cent of the cases. Twenty to forty milligrams of radium element were used. Gamma rays only Avere utilized. The radium was apiilied over the closed eyelid at a distance of two centimeters for two hours. W. S. Franklin and F. ('. Cordes have apparently confirmed these results. These authors have treated thirty-one cases of immature cataract of wliicli S-l.o j)er cent showed a (diange for the bctler ranging from an improvement of three to four letters on the test chart to a complete dis- ajipea ranee of the ]U'ocess. They used the following technic. At a dis- ■2'J7 298 RADIUM THERAPY tance of 1.2 cm. from the eye, 10 mg. hours were given twice a week for four weeks and then once weekly until the process was stationary. The gamma rays from about ten milligrams of radium element contained in a glazed plaque having an ai-ea of 50.26 square millimeters Avere utilized. OTOLOGY In granulomata and papillomata in the external auditory canal, radium is frequently of great value. I have treated a numljer of cases in Avhich recovery has been brought about. Fifty millieuries screened with 0.5 mm. of silver plus 0.5 mm. of gold may be used in the external auditory canal for six hours in periods of one hour each on alternate days. In "tinnitus aurium" radium has not been of marked benefit. Little impro1»ement can be expected from the treatment of "chronic deafness" due to mid- dle ear disease. I have treated in conjunction with 0. T. Freer a number of cases of this character without definite benefit. RHINOLOGY Carcinoma and sarcoma of the nasal passages have l)een considered under Radium in General Surgery. In chi-onic ethmoiditis with recur- ring polypoid degeneration, radium has been used with good results by 0. T. Freer and T. ]\Ielville Hardie. A platinum tube having a wall thick- ness of 0.3 mm. and containing 50 mc. of radium emanation may l)e inserted into the ethmoid sinus f(n- five hours in periods of an hour each. LARYNGOLOGY A. Malignant Growths of the Larynx Carcinoma and sarcoma of the larynx have been mentioned under Radium in General Surgery. The technic of intralaryngeal radiation is descril)ed l)elow. r>. Benign Growths of the Larynx 1. Papilloma cf the Larynx. — Abbe has reported a remarkable and suc- cessful case of i)apiIloma of the vocal cord in which complete relief was obtained. The singing voice Avas restored and recovery has been main- tained for moi-e than ten years. In tliis ])atient a preliminary tracheot- omy was performed and aiu'sthesia was continued through the tracheot- omy opening during the radiiun application. One hundred milligrams of radiinii were a])plied, by means of a wire i)assed througli the trache- otomy wound into tlic mouth, for thirty minutes. In a personal communication to the writer. Abbe states that other siinihir cases have since been treated and have done equally well. OPHTHALMOLOGY, OTOLOGY, AND LARYNGOLOGY 299 G. B. Now, of the Mi\yn Clinie, states that "the treat luciil of miilti])lc papilloma of the larynx in children lias l)eeii imi)rove(l woiulcrfully by the addition of radinni. "The patient is suspended willi llie Lyiu-li suspension appai'atus, tlie ])apilh)nias are cleared out, and wjiile thus suspended the radium is placed in the larynx in children with tracheotomy." 2. Angioma of the Larynx. — G. B. New, of the Mayo Clinic, has re- ported the results of the trealnient of an an<>ioma of the larynx occurring: in a child. The gi-owth caused "dys])nea Avhich would have been very difficult to benefit in any other way. The angioma was entirely cleared up l)y the external a])plication of radium." 3. Chronic Infections. Laryngeal Tuberculosis. — The results of treat- ment of this condition have varied. In a ease of laryngeal tuberculosis treated in conjunction with Dr. O. T. Freer several years ago the result was not favorable. In this case the radium was held in the larynx by means of an intralaryngeal applicator. Fifty milligrams screened with one millimeter of silver was applied in periods of ten to fifteen minutes each, a total exposure of three hours being given. In another case in which two small lesions were present on the right vocal cord complete resolu- tion was obtained by external applications. In this case, two hundred millicuries screened Avith two millimeters of lead and placed at a dis- tance of two centimeters were applied for thirty lioui-s in periods of fif- teen hours each. Technic of Laryngeal Applications. — Surface Had iat ions otwr tJie Lar- !/ii.r. — 11 is fre(|U('ntly ixissihh' to influence favorably benign and malig- nant tumors of the larynx hy sui'face radiations alone. Benign tumors may be cured by surface radiations alone but malignant lesions retiuire intralaryngeal radiations as well. At a distance of '■] chl. 250 mc. screened with 2 mm. of lead may be applied for twenty lioui's in jx-i-iods of ten or more hours each. Four hundred mc. may be a])i)lied at a distance of 6 cm. for thirty hours in several periods. IntraJari/ngeal liadiatwns. — In the technic of intralaryngeal radiations, a strong vise-like clamp (Fig. 162) is fastened to the forehead by a strap acting- as a head-band. A metal forehead plate serves as a base for the clamp. Long stemmed applicators (Fig. 163) made of copper tubing eiuling in a holdei- (Fig. 164) securely grasp the screen containing the emanation tube which is thus i)laced exactly upon the desired area in the larynx. In making a laryngeal application the larynx is first anes- thetized with cocaine flake crystals made into a mud by contact with a slightly moist swab. The local anesthesia is then i-einfoi-ced with anes- thesine powder insufflated into the ])haryux and laiwux. In order to introduce the emaiuition tube into the larynx, the applicator is sci/cd l)y the tlininh-plate (Fig. 163) and the sci-ccn is inserted into the larynx with tlic aid of the laryngeal niin-or. Except in the case of papilloma of 300 RADIUM THERAPY the larynx in chiUlrcii, neither direet hirynyoseopy m)v suspension hir- yngoscopy is needed. When the screen has been introduced into the larynx, an assistant passes the stem of the applicator into the space be- tween the jaws of the clamp which he closes upon the applicator stem, thus fixing- the screen in place. Usually the tube may be retained for ^'S- '^2. — The Freer clainp for the intralaryngeal application of radium. The clamp seen from above aftxed to the forehead plate of the head-strap and open to receive the tubular stem of the applicator. r.A.HAROY^Ca I'ig. 163. — The applicator held in the jaws of the Freer clainp with the screen containing radium emanation in the glottis as indicated by heavy dotted lines. OPHTHAr.MOI.OOY, OTOKOCV, AND LARYXOOLOGY 301 ffoni ten to sixty miimtcs witliout i-ctclihi^ oi- disti-oss. The hollow stein carrying the emanation tnbe is attaelied to an electric suction pump ■vvhicli serYes to keep tlie throat constantly free of saliva and secretions. The use of moderately large doses is of great value in the treatment of feeble patients. An exi)osui-e of 400 nic. hours may he given in the course of a Aveek or more. Witli intralaryngeal and surface radiations comhiiu'd I ha\e treated, in conjunction with Dr. O. T. Freer, 19 carcinoiiiata of the lai-ynx. Of these 5 were extrinsic, 14 intrinsic. Clinical recovery has occurred in 9 of the intrinsic and in one of the extrinsic cases, and has been main- tained for from 2 to 12 m(»iitlis. One ca.se recently developed a metas- tasis in the humerus but tlie larynx is clinically well. Of the remaining F.A.HARDY^CO. rig. \Ci-i. — A. Kiianul silver lulu- iimtaiTiinK capillary glass emanation tiiln-: B, Screen fastened to tubular copper applicator at a — a by means of cojiper wire soldereil into grooves at sides of ap- plicator and run through eye of screen. Screen holds one enamel tube only; C, silver screen with cap; wall thickness of screen 1 mm. These screens hold from 2 to 6 emanation tubes and are identical with the screens used for surface radiation previously illustrated; P, silver screen seen on edge, fastened into notch of holder by No. 24 coi)per wire a- — a shown by heavy dotted line to indicate passage of wire through holes passing through jaws of notch, walls of screen, and its cap and thence into interior of tubular holder through holes at a — a. The wire is shown twisted in the saliva hole of the holder in order to lock the screen safely to the holder; H, holder and screen seen on the flat to show the holes at (a) connected by a groove, the holes being bored to pass copper wire through jaws of notch, .screen, and its cap and thence into the interior of the tubular part of the holder; P. socket holder to hold screens for use in the glottis. The holders must he individually made to tit each screen. The advantage of this holder lies in the firmness with which it grasps the screen. 9 ])atients, seven wei-e too far advanced for more than palliation and two who have been under treatment for only a short time were also of the advanced type. In one case of multiple papillomata of the right vocal cord and in one ease of diffuse, hypertrophic laryngitis with great deform- ity accompanied by loss of voice for fifteen months, complete recovery occurred. In both cases the voice was restored and the larynx shows no trace of the pathological process, the cords appearing white and normal. 302 RADIUM THERAPY A rapidly growing- sarcoma of tlie right vocal cord recently under treatment completely disappeared leaving the larynx nearly normal ex- cept for some cicatricial retraction. Relapses are to be anticipated in a certain percentage of the cases of malignant tumors of the larynx. The intralaryngeal treatment is usually i-einforced by deep gamma radiations applied to the surface of the skin over the laryngeal region. The applicators and the technic of intralaryngeal radiations which we have just described have been devised and made of practical utility by Dr. Otto T. Freer. Hypertrophy of the Tonsils C. A. Simpson, \V. A. Wells, the writer, rind ollicrs have found radium of value in tlie treatment of certain cases of liyperti'ophied tonsils. Simpson has used a double strength dermatological applicator contain- ing 30 mg. of i-;i(liuiii ch-mcnt. This was wrap])ed in rubber dam and applied unscreened for one hour. Wells has insei'ted radium contained in metal needles into the tonsil. In some cases, 100 mc, screened with 1 mm. of silver plus 1 mm. of rubber may ])e applied for 1 hour to each tonsil. The normal tissues of the throat must be carefully protected. In selected cases, radium treatment may l)e substituted for operative removal of the hypertrophied tonsil. CHAPTER XIX RADIUM IX DISEASES OF THE DUCTLESS GLANDS A. LEUKEMIA Renon, Doo-rais and Deshnuis wore aiiioii<»' tlie first to use radinm in tlie treatment of niyelooenous lenkoniia. Tlie radium Avas applied di- rectly over the spleen. After referriiit>' to twelve cases treated by other French Avorkers, these authors reported five cases under their own care in which satisfactory vtMuissions were obtained. Of the five cases re- ported, death occuri-ed in two, two years and two months after the first exposure. Two cases were in o-ood health six months after the first treat- ments. In the fifth case, splenectomy had been performed prior to the radium treatments. In spite of this, however, radium applied over the splenic area produced a marked decrease in the leucocytes, w^hich fell from 143,000 to 21,500. This effect may be accounted for, most probably, by the exposure to the rays of the large volume of blood circulating in the cavity of the abdomen. Later, Renon, Degrais and Tournemelle reported a sixth case of leukemia in which radium was used with benefit. Numer- ous cases have been reported more recently by Giffin, Hayward Pinch. Ordway, Pealxxly and many oiliei-s, iiieluding myself, in whieli a favor- able influence has l)een exerted by radium. Giffin has reported thirty cases and Peabody has observed thirty-six eases of leukemia in which radium treatnu^nt was used. T have treated fifteen cases. All of the cases just referred to were treated in the usual way. i.e., by the surface application of the radium over tlie spleen. The beneficial effects of the radium treatnu'iit of leukemia are quite uniform. A certain degree of improvement occiu's in the genei'al condition of practically all of the cases. Headache may be relieve and strength may occur so that the usual occupation of the patient may be resumed. The effect on the spleen is to reduce it pei-ceptibly in ]n-actieally all cases. Frecpiently the spleen becomes almost or (|uite nonjialpable. The spleen usually shows the greatest reduction in size in about one or two niontlis from the beginning of the treatment. The blood picture shows very definite ert'ects of the treatment. The number of leucocytes usually begins to decrease in from one to three days after radium is applied and may progressiv(>ly continue to diminish for several days or even weeks after the exposin-e. In one <»f Peabody 's 303 304 RADIUM THERAPY cases of myelogenons leukemia in which radium was applied on the first and thirteenth days only, the leucocyte count fell from about 100,000 to 6,000 in twenty-five days. In a case of chronic lymphatic leukemia, previously reported by the writer, the leucocytes fell from 113,000 to 5400 in 28 davs. Many other even more striking illustrations of the w \ i;;,, K,5 —Chronic lymphatic knikemia. Greatly enlarged cervical and axillary lymphatic glands. White blood count 113,000. Photograph taken January 12, 1917. Patient referred by Dr. Charles A. Hlliott. improvement in the leucocytosis might be cited. With regard to the differential leucocyte count, the relative as well as the absolute percent- age of myelocytes is usually strikingly reduced. The relative percent- age of neutrophilic polynuclears remains about the same but the abso- RADIUM IN DISKASKS OF DrCTLKSS GLANDS 305 lute number is usuall.v markedly diminished. The relative percentage of small lymphocytes shows an increase after the reduction in the leuco- cyte count but the absolute count of tlie small lymphocytes is much diminished. The relative percentage of large moiiomiclears is usually increased. Fig. 166. — Patient in Fig. 165 sliowing iLiui.ssion of tlic iliscasc alter radium treatment. The cervical glands have l)ccome practically normal and the axillary glands are markedly reduced. White Ulood count 7,.S00. Photograi)h taken February 3, 1917. In the majority of j^atients, there is usually an improvement in the red blood count and in the percentage of hemoglobin. If hemorrhage, such as epistaxis, ])uri)iira, etc, is ])r('scii1 it usually ceases. While it has been held bv some tluit licuiori'liauc mav even be caused bv r;idium treatment. 806 RADIUM THERAPY I believe this to be very unlikely. In any series of cases, hemorrhage may occur, but as it is a symptom that is not uncommon in the natural course of the disease, it is difficult to ascribe it to the et¥ects. of radium. Technic of Treatment. — The best guide to the amount of treatment is furnished ordinarily by the condition of the white blood count. One should not attempt to bring the leucocytic. count down to normal. Prob- ably a count ranging between 15,000 and 30,000 will be found to accord witli a satisfactory clinical condition. Peabody has stated that patients seem to do well clinically if their white count is not over 50,000. Exces- sive radiation may result in actual harm. The technic of the application of radium is simple and while similar results may be obtained by different methods, it is our l^elief that too large doses should be avoided. The radium may be applied to differ- ent areas of the spleen successively, or to the lymphatic glands, as the case may require. Although some advocate radiation of the long bones in myelogenous leukemia, this has not been thought advisable, nor in our experience necessary in order to produce remission. Ordway used, in one of his cases, an applicator of about ''double" or "triple" strength f50 to 60 mc. concentrated on 4 square cm.). With this apparatus the spleen was covered by radiating successively every 9 square centimeters of skin surface. The metal filter was 3 millimeters of lead and the distance (obtained by 15 to 20 thicknesses of filter paper or 25 to 30 layers of o'auze) Avas apparently about 5 to 10 mm. additional. Exposures of four to six hours over each area were given. Three series of treatments were given four to six w^eeks apart. Great symptomatic improvement followed, although the patient died about eight months after the first series of treatments. Gif^n has used a technic similar to that just de- scribed. Fifty to one hundred milligrams of radium element were em- ployed. The screening finally used was two millimeters of lead plus one half inch of Avood. The enlarged spleen was mapped out into squares 3x3 cm., each square receiving successively two to four hours' radiation. The total length of time for the complete radiation of the spleen varied from twelve to forty-eight hours, the usual time being twenty-four to thirty-six hours. The exposure was repeated every week until remission was progressing satisfactorily. Peabody has stated that the experience of himself and his coworkers does not enable them as yet to state definitely the best dosage. There is some evidence, however, leading them to believe that one or more powerful treatments followed by an intermission of several weeks until the effects of the radium are over, are preferable to repeated small doses. 'Sly experience leads me to prefer this latter method. Ordinarily 200 millicuries (1^4 ™P- to each square em.) screened with 2 millimeters of lead and at a distance of 3 centi- meters may be used. An exposure of six hours twice Aveekly may be given over successive areas until the splenic area, or in lymphatic leu- kemia, the area over each group of lymphatic glands has been covered RADIUM IN DISEASES OF DTTCTI.ESS GLANDS 307 or until a satisfactory diminution in the leucocytes is evidoul. The course may ])e repeated in six weeks but may he given earlier or later as thought advisal)h>. It must he emphasized, however, that great judg- ment is required in detei-mining the size of the dose and the frequency of its repetition. A'arious factors must be considered, these being prin- cipally the etfeet of the treatment on the general condition, on the size of the sph^en and especially the effect on the white blood count. R-tdium. applied to the spleen in the manner indicated, may cause a constitutional reaction, such as nausea, vomiting, malaise and headaclu\ Tli(>se symp- toms usually pass off within twenty-four hours. An excessive amount of treatment mtiy result in marked leukopenia and an increase in the anemia. Thes(^ symploms sliould be guarded against by caution in re- peating the exposures. If they do occur or if hemorrhage supervenes, transfusion should be resorted to. Locally a skin reaction may occur, but with the technic advised this will be slight oi- absent. In applying a radium pad to the splenic area, the outer aspect of the pad should be protected so that the patient's arm will not rest inad- vertently on the radium tul)es. Results of Radium Treatment of Leukemia. — Complete remission or at least a satisfactory clinical condition may be expected in from three weeks to three or four months. Patients may remain apparently well for several months or even several years. Kecurrences may take place l)ut these usually yield, at least for a time, to further treatment. Surgi- cal removal of the spleen is probably advisable in selected cases when the remission of the disease is at its height. In twenty of Giffin's cases, eighteen of which were ti-eated with radium, splenectomy was performed when the reduction in the size of tlie spleen rendered the operation advisable. One patient died as the result of operation. Ten patients were living and in good general condition, nine to nineteen months after the splenectomy. Giffin concluded, however, that the natural course of the disease was probably not altered by s])lenectomy, although the patients may be made more comfortable by the oi)eration. In addition to the usual method of treating leukemia by exposing the spleen oi- lymphatic glands to surface radiations, a few workers have inves- tigated the effects of radium when administered constitutionally. Tlie re- sults of this method of treatment have varied. Yon Noorden and Falta did not obtain l)eneficial results from the inhalation of radium emanation. Proescher and Alin dei)osit dissolved in water has also been injected by a few workers. For the present, liowever, the method of treatment of leukemia by exposure of the spleen or lymphatic glands to surface radiations is to be prefei-red. Eadiuni treatment is in-<.l)ably the method of choice, in the treatment of leukemia at tlie pi'csent time. It 308 RADIUM THERAPY sometimes succeeds in producing remission when all other methods, in- clnding- tlie use of l)enzoI and x-rays, have failed. B. HODGKIN'S DISEASE (LYMPH ADENOMA) The affected glands in Hodgkin's disease frequently disappear very promptly. In only one of eleven cases treated have Ave seen rebellious- ness to the treatment. In two cases of that form of the disease, in which nodular tumors a]ipear on the hones (sternum, skull bones, etc.) very marked susceptibility to the radium i-ays was noted. In scA'eral cases Ave haA'e seen remissions Avhich haA-e persisted for more than one year. It is probable, howcA'er, that recurrence takes place sooner or later in most cases. The ti-eatment is ordinarily given by means of deep radia- tions. The enlarged glands may be treated serially in order to spare the patient as much as possible the systemic reaction (nausen. malaise) Avhich frequently folloAvs heaA'y doses. Four hundred millicuries screened Avith 2 millimeters of lead may be used at a distance of 6 centimeters for a total of 30 hours in periods of ten or more hours each OA-er each area. The concentration of the radium may be 5 mc. per square centimeter. Treatment may be giA'en twice Aveekly or less often until the areas involved have been radiated. Occasionally less powerful treatments may be given for three or four days in succes- sion if the systemic disturl)ance is slight. C. GOITER In the A'arious types of goiter, radium treatment may be helpful. In the simple parenchymatous type there is general enlargement of the thyroid gland and the follicles, AA'hich are usually ncAvly formed, contain colloid material. The results of radium treatment in this type may be A'ery beneficial. The A'ascular type of enlarged thyroid may also respond Avell. In favorable cases the neck may decrease in size several centimeters. In the type of goiter in Avhicli large cysts occur, the Avails of the cysts fref|uon11y uiid('rgf)iiig calcificatidu. but little benefit is to be expected from radium Ireatment. Exophthalmic Goiter Abbe, of XcAV York, treated the first case of this disease Avith radium in 1005. Following Abbe's report many other authors, including Aikens, Hurrows. ('lagett. and Dawson Tunu'r have i'e])orted favorably upon the i-esults of radium ti-eatment. Radium may be used Avhen the oi'dinary methods of treatment prove unavailing or A\hen operation is considered inadvisable. In eases that respond favorably, improA'ement in all the toxic symptoms may be noted in three to six Aveeks and in some eases, vci'v much more (juiclx-ly. Tacliycardia, tremor and exophthalmos are RADllM IX DISEASKS OF Dl'CTLKSS GLANDS 309 fre((uciitly (liiiiiiiislicd. The liii'ce of impi-oNciiient has l)een l)rought a])ont l)y radium. Tt luis l)een lu'ld Ihat opci'al ion is rendered more difficult by previous radiation. It nnist he renuMubered that strik- ing remissions may occur in the natural course of the disease so that it is sometimes difficult to .judge of the effi'cts of treatment. Technic of the Treatment of Goiter. — The metliod of ti-eatnu-nt involves the use of nuxlei'ately deep ])enet rating rays. Aikens, who has observed about one hundred cases, advises in the beginning of treatnuMit a total exposure of from 150 to oGO milligram hours. Subse(|uent coui-ses of 50 to 150 milligram hours may l)e given. ^lany othei- authoi-s use larger doses tlum those just indicated. I ordimirily use ]U)t less than 150 milli- cnries, screened -with 2 millimeters of brass and placed at a distance of 3 centimeters. Five millicuries nuiy be concentrated on each square centimeter. A total exposure of twenty houi-s on each of three areas is giv'cn. In certain cases of large goiters we use 500 millicuries con- centrated on an applicator having a superficial area of fifty srpiare centi- meters. This is screened with 2 millimeters of brass and applied at a dis- tance of 6 centimeters. An exposure of fifteen hours ma\' be given to each lobe and to the isthmus of the thyi'oid. The three exposures should be given several days ajiart. Depending upon the severity of the disease, the dose may be diminished or increased in different instances. In some cases, following the treatment there is an exaggeration of the symptoms for several days or even for a week or more. Imprt)vement then usually sets in and by the end of a month (u- six Mceks may be \-ei-y decided. The course of ti-eatment may be repeated at inter\als (»f six or eight weeks. Snbseipient courses of tr-eatment may be of less intensity. The amount of treatment nuiy be regulated by the basal metabolism test. In addition to the radium treatnu^nt, sup])lementai'y nu'asures iiudud- ing rest, diet and suitabh* di-ugs should be used. 1). ENLARGED THYMUS GLAND Drayton a?id Uenblein ha\c treated with radium :>4 cases of eidarged thymus gland in children. In ever\' instance tliei'e followed a prompt and lasting disappearance of all symptoms. 'JMiese authors stale that ''eveiy infant Avho has Spieer sjx-lls' ^\•ho has habitnal attacks of cough- ing, choking, dyspnea, oi' cyanosis should have an x-ra\' examination of its chest in the hope of fiiidini;- a condilion (pathologically eidarged thymus) which is so easily aiul satisfactorily cured." Their technic consisted in using 100 miligrams of radium ehnnent screened with 0.5 mm. of silvei'. The I'adiiim was applied at a distance of one half inch from the skin to four difTerent points over the thymic jirea and allowed to remain for tAvo hours over each point. CHAPTER XX RADIUM IN INTERNAL MEDICINE Radiuni and tlioriuni X are the two princijial radioactive substances used in internal medicine. The Inoloo'ic action of these two substances is similar but not absolutely identical. Proescher states that while all radioactive substances produce a more or less marked numerical increase of the red blood cells, thorium X is the only one causing pronounced destruction of the leucocytes. The more rapid decay of thorium X as compared "vvith' radium explains its more intense biologic effect. The investigations of the effects of tliorium X have enabled us to fill up some of the gaps in our knowledge of the effects of radium. In the fol- lowing pages its action will be considered in connection with that of radium. We may discuss the internal administration of radium under the fol- lowing headings: (a) the administrati(ni and elimination of radium, (b) its physiologic effects, (c) morphologic changes in the tissues caused ])y radium, (d) therapeutic indications. A. THE ADMINISTRATION AND ELIMINATION OF RADIUM (]) The Administration of Radium Radium may l)e administered either in the form of radium salts, radium emanation or the active deposit. The effects of ])otli the salts and the emanation appear to be practically identical except that the action of the emanation is naturally more evanescent and therefore per- haps more desirable on account of the rapid elimination from the body of a gaseous elemeiit. Less experience has been had A\"ith the actual administration of the active deposit but it seems probable that the effects are the same as those of the salts and the emanation. Administration of Radium Salts Radium salts are usually administered by gi^•illg, by mouth, water con- taining the salt in solution or ])y the injection of a solution of the salt intravenously. The drinking Avater is usually of a strength of one microgram of radium element to 30 c.c. of distilled water. The ordinary dose is 120 to 240 c.c. per day. For injecting intravenously, 10 to 100 micrograms of radium element in the form of a soluble salt dissolved in 2 c.c. of normal salt solution may be used. Injections are usually given every week or ten days until the patient has received 300 micro- grams. 310 RADIUM IN INTERNAL MEDICINE 311 Administration of Radium Emanation Radiitin ciiiaiiatioii nuiy bo adm'misU'i'cd by incans of (lriiil\iii'iven every few days by moutli to replace that ^\■lli(dl is eliminated. H. PHYSIOLOGIC EFFECTS OF RADIUM Exjieriments on different animals as \\ell as on human beiniis to deter- mine the effects of radium ha\e been carried out by l^ellin^^ham-Smith, Cameron and Viol, Dominici and Faure-Beaulieu, (iud/.ent. Jaboin, Proeseher, Salant and i\feyer, Wickham and Dejirais and many others. We may first consider the effects of therapeutic r/o.sr.s. These effects may be discussed under the following- headings. (1) tlie genei-al ])hysiologic effects, (2) the effects on the heart, circulation and respiration. (3) the effects on metabolism. (1) General Physiologic Effects One of the chief subjective benefits derived by many i)atients taking radium in therapeutic doses is a feeling of "bien etre." Whether this is entirely subjective, it is, of course, difficult to say. In arthritic cases especially, a certain amount of relief from pain may be exi)erieneed. The majority of patients taking radium emanation solution have a definite diuresis and a slight laxative eff'ect is sometimes observed. Some patients experience a detinite so-called "reaction." S. I.owenlhal lii-st called attention to this phenomenon. The reaction is characterized 1)y an aggi-avation of symi)toms, after a certain amount of treatment has been given. There may be, e.g., an exacerbation of any joint symptoms that have been present. (Jeneral dist ui-bances, inchiding "tired feel- ings," "malaise," and a desire for sleep, may occur. In other patients there nuiy be excitement and sleeplessness. These sym])toms pass off after a tinu' if the treatment is discont iniu'd. According to (iud/.ent, these ])ln'in)nu'na ai-e f I'lcpient ly of favorabk' prognostic import. (2) Effects on the Heart and Circulation The effects of a radioactive Ringer's solution on the isolated frog's heart have been studied by ^Maass who found that tlu' heart became di- lated and its action arrested. By rinsing out the heart witii normal 314 RADIUM THERAPY Ringer's solution, its normal activity returned. The heart shoAved less activity with each experiment, indicating according to tliis investigator, a lowered resistance. In nuimmals, howevei', Plesch and Karczag could not dui)licate these results. Zwaardemaker has described a new and hitherto unknown effect of the radiations on the heart. Tliis author found that a frog's heart kept actively beating by artificial circulation ceased to pulsate if the potassium was extracted from the circulating medium. If the heart Avas then radiated Avith a fcAv milligrams of radium for thirty minutes it again began to beat. If a certain quantity of uranium salt Avas added, the heart again stopped. RencAved radiation again started the action of the heart. While these experiments are extremely interesting from a scientific standpoint, no therapeutic deductions have as yet been draAvn from tliem. Certain of the experiments on blood pressure have a practical aspect. In A'arious experiments on dogs and human l)eings carried out by LocAvy, Plesch and Gudzent Avith inhalations of radium emanation and injections of thorium X, the blood pressure in general Avas markedly decreased. According to Gudzent, the decrease in blood pressure, Avhich may be loAvered for long periods and may even become and remain normal in certain gouty and arthritic patients, is due to the destructiA^e effect on the A^asoconstrictor sul)stances produced by the suprarenal glands. Respiration. — In animals and in healthy human beings, no especial effect on the respiration from therapeutic doses can be observed. In cardiac dyspnea and in ])n('um()nia, Plesch has reported an acceleration and increase of respiration. (3) Effects on Metabolism The influence of the administration of radium on metabolism lias been studied by Falta, Gudzent. Krieg, LoAventhal, Plesch, Rosenbloom, Wilke, and many others. The investigations tend to shoAV that the excre- tion of uric acid and of purin is increased. The entire nitrogen excretion is also increased. FolloAving an injection of one hundred micrograms of radium element intravenousl.y, Rosenl)loom found that there Avas a con- siderable increase in the ethereal sulphur output. In three patients Avhose metabolism Avhile taking radium emanation Avater (3 ounces, five times a day or 20,000 Mache units in all) Avas studied by McCrudden, no marked metabolic changes Avere made out. Only one definite change Avas observed — a slight increase in the rate of creatinin excretion. The results of the studies of various authoi-s have shoAvn, in general, marked differences in the effect on metabolism and in some patients little or no effect has been observed. We may also nuMition here tlic investigations of Knudson and Erdos who studied the metabolism of a case of leukemia that Avas being treated by surface applications of radium over the spleen. The conclusions of these authors Avere as folloAvs: The excretion of KADIIM l.\ l.NTKHNAL MKDICINE 315 nitrogen, iire;i, iiinnioiiui jiiid |)li(>s|)Ii;ites Avas oiKirniously iiu'rcased after the application of radium. The uric acid output -was only slightly in- creased compared to the other nitroj^enous bodies. Surface applications of radium over tlie spleen accelerated the disintegration of nuclein tis- sues resulting in the increases mentioned above. An increased production of uric acid that was anticipated on account of the disintegration of nuclein was not observed. The effect on the phospliates was remarkable, there l)eing at times an increase of four hundred per cent over the excretion observed at the Ix'ginning of ti-eatment. We may now consider the effects of toxic doses of radium. The follow- ing description of the effects of a lethal dose has been given by Gudzent : If an animal, e.g., a rat, receives an injection of a soluble radium salt of sufficient strength, no changes are at fii-s1 a])i)ai'cnt wliich indicate injury to the organism. The animal eats, sleeps, moves about, and passes lU'ine and stools in a normal manner. In a few days, hoAvever, the picture changes. The animal api)ears to be ill, i-efuses food, and sits about in a "crumpled up" position. Its respiration increases, fever is present, and it passes bloody stools and urine. The animal then grows weaker and weaker and usually dies in convulsions. As to the exact cause of death it has been held that it may be due to the effect of the i-adium as a toxic substance. Experiments with ])arium, an analogous chemical element, do not bear out this view. To cause death Avith l)arium one must use a dose several hundred times gieater than the lethal dose of radium. The toxic symp- toms are also dissimilar. The death of the animal, therefore, after a sufficient dose of I'adium intei-nally, a))pcai"s to be due solely to the effect of the radiations. Uudzent has estimated the lethal dose of radium when injected in the form of a soluble salt to be about .007 mg. of radium element per kilogram of l)ody weight. I'or a body of 70 ly the inhalation method, Proescher and A'iol found thai a concentration of 26 millicuries of emanation ])cr liter of air (70 million Machc units) produced death in animals. La/aru.s-Barlow exjxiscd animals to the gamma rays of five grams of radium bromide. The minimum lethal dose of gamma rays for the rat was an exposui'c of six hours, the animal dying about foi-ty-two hours later, l-'or the i-abbit an exposure of nine to ten hours Avas necessary. 316 RADirM THERAPY C. MORPHOLOGIC CHANGES IN THE TISSUES CAUSED BY RADIUM iDasmuch as tlie effects of radium taken internally are due to the action of the rays, one Avould expect that similar changes Avould be pro- duced in the tissues whether the radium is administered internally or radiations are used externally. Experimental investigations have proved, in a general way, the truth of this supposition. There is, of course, this very evident difference : in the case of the internal administration of radium, the whole organism, and especially its most radiosensitive struc- tures, is affected by the rays, but if radiations are used externally, the effect is practically limited to the part irradiated. By radiation of animals in tofo. however, effects may be produced that are practically identical with those caused by the administration ol radium. We may now consider the changes produced in dift'erent tissues. The Blood Vessels Lethal injections into animals of thorium X produce an intense hyperemia of almost all the organs. Hemorrhages frequently occur; sometimes a single vessel is affected but at other times the hemorrhage may extend over large areas. The capillaries and smaller vessels show the most marked injuries. The Blood, Leucocytes If small doses of radium salts (Viodu uiK-) '••' thorium X (liouo to Vioo niiR^-) ai'6 injected intravenously or if inhalations of radium emana- tion (5 to 100 or more Mache units) are given, a transient leucocytosis appears a few hours later. The number of leucocytes may even increase to 20,000 (Gndzent and Levy). The next day, after a slight decrease to below the initial amount, the leucocytes become normal. If larger doses of thorium X (0.5 mg.) are injected, leucocytosis develops quickly. A leucopenia appears later. The leucocytes may decrease to 1000 or even lower according to the dose. If very large doses are administered the leucocytes may even disajipeai- from the l)lood altogether just prior to the death of the animal. According to I'rocsclicr and Alm((uest, thorium X has n more destruc- tive effect on the leucocytes than radium. With superfatal doses of radium tliese authors wei-e unable to destroy all the circulating leu- cocytes or myeloid cells of the bone marrow. Erythrocytes In contradistinction to tiie leucocytes, the red blood cells are not markedly sensitive to injections of radioactive substances. After small HADir.M IN IXTKHXAI, M KDK M N K 317 closes, no eliano-e at all, as a rule, is seen. Sometimes, however, there may be an inei-ease in number of erythrocytes as oliserved l\v Doniiniei in tlie horse and Brill and Zehner in dogs and ral)bits. Tlie last 2 autliors found that the erytlirocytes were increased in some cases to 13 million per c.c. This increase may be maintained for weeks. Tlie hemo- ololnn was also increased but iu)t proportioiudly 1o the increase in the number of erythrocytes. Pi'oesclier and Almquest have reported similar results. By the injection of lai'<>er doses of thorium X, the red lilood cells may be damao-ed so thai both a numerical decrease and a decrease in hemoglobin may occur. In pathologic conditions, such as secondary and pernicious anemia, the erythrocyt(v>; a])])ear to be more sensitive than in normal iinlividuals. Proescher fouiul that in such cases tlie injection of soluble radium salts (0.1 to 0.4 mg.) increased the red blood cells to noi'inal iu a few days. Oudzent has rcjioi-ted the sann^ effect from the injection of small doses of Ihorium X (0.01 to 0.1 mg.). Spleen, Bone Marrow and Lymphatic Glands Gudzent states that the key to the understanding of the changes in the blood picture lies in the knoAvledge of the changes in the organs mentioned above which are, as we have seen, very radiosensitive. The changes produced by radium administered internally are practically identical with those caused by external radiations. These changes have already lieen described in a ]n-evious chaptei-. Suprarenal Glands Falta and his coworkers and later von Donuii'us and Salic called at- tention to the changes produced in the suprarenal gland and its func- tions. Injections of thorium X produced, in geiuu-al, degenerative changes together with hemorrhages in the cells of these organs. The blood pressure of the animals was reduced in consequence of the dis- appearance of the substances causing vasomotor constriction. The effects on blood pressure depended on the dose but both small aiul large doses, after an initial increase, caused a decrease. In certain cases, the blood pressui'c rose again but did not attain to the jioint initially ]u-csent. Other Organs The effects of injections of i-adioactive snhstanccs on other organs — heart, kidney. ])anci'eas, etc. — are nuich less ])i-onouiiced than on the previously mentioned structures. Traces of injury to tlie cells of certain areas may be detected but these <-hanges are never of a general nature. Functional disturbances probably occur but these have not been as yet sufficientlv in\-es1 igated. 318 RADIUM THERAPY Effects of Large and Frequently Repeated Injections A problem of importance is that of the possible constitutional effects of large and frequently repeated injections. The experiments of Silva Mello tend to throw some light on this question. This author found that the injection of a single dose of thorium X, if not immediately fatal, might so injure an animal as to cause its death in the course of a few weeks or months. The most obvious effects that were observed in the meantime were (1) leucopenia, (2) anemia (decrease in erythrocytes and hemoglobin), (3) marked decrease in weight. Evidences of regenerative processes were observed also in the bone marrow. If such an animal re- ceived a second injection, which was not large enough to cause death by itself primarily, the animal quickly succumbed. The blood, spleen, bone marrow and lymphatic glands showed evidences of the greatest damage. It may be assumed that the animal was sensitized by the first dose. Equally interesting were the results of repeated injections of tho- rium X into animals in doses that were not large enough singly to cause perceptible severe injury. In these animals a certain degree of resist- ance apparently developed. Consideral)le quantities could be borne without any of the previous symptoms (leucopenia, anemia, loss of Aveight) developing, until, after a time, the animals rather quickly suc- cumbed. In these animals the spleen was the only organ showing marked effects. The bone marrow was nearly always unaffected. Inasmuch as it may be assumed that the effects of repeated injections do not differ materially from those of repeated external radiations which are delivered over very extensive areas, these experiments show the need of caution in the use of powerful and repeated exposures for therapeutic purposes. They also suggest the need of care on the part of the operator who is handling large quantities of radium in order that he may avoid injury to himself from the persistent exposure to the rays. 1). THERAPEUTIC INDICATIONS The fullest details as to the use of radium and other radioactive sub- stances in intei-nal medicine are to be found in the recently published moiiogra|)li of Falta. Among the many diseases in which radium has been used with alleged benefit are the following: 1. Artliritis deformans, articular rlicumatism (sul)aeuti' and chronic) and various other ty])('s of arlhi-itis. 2. Gout. 3. ]\ryalgia ("muscular rheumatism"), neuralgia and neuritis (sciatica, talx'tic ])ains, etc.). 4. "High blood pressure," arteriosclerosis, angioneurotic edema, neu- roses of the heart, myocarditis. KADIIM IX INTKRXAL MKOICIXF, 319 5. Certain chronic inflammatory and siippui-ative processes. 6. Bright 's disease and diabetes. 7. Leukemia, Hodgkin's disease, and various forms of anemia (per- nicious anemia, chlorosis, etc.). 8. Dermatoses (psoriasis, scleroderma). 0. Malignant disease. 1. Arthritis Deformans. — Tt lias h)ng heen the custom for sufferers from chronic joint diseases to visit springs in different parts of the world and drink tlie waters. With the discovery that most of these springs contained radium emanation in solution it ))ecame of gi-eat interest to determine the effect of radioactive substances artificially prepared. Tt may be noted that none of the springs at the various health resoi'ts con- tains more than the most minute quantity of radium emanation (about 1 to 30 millicuries per million quarts). It Avould seem, therefore, that radioactive substances in doses sufficient to pi-oduce definite physiologic effects might be of even greater benefit. Ha\\vard Pinch (London Ra- dium Institute) has reported very favorable results from the administra- tion of radium emanation water especially in arthritis deformans. In this author's experience pain Avas relieved and the mobility of the joints was increased provided no bony or cartilaginous changes had occui-red. In some cases the results were quite remarkable. Cameron and many others have also seen favorable results in various types of arthritis. Gudzent, wlio has made one of the most extensive reports, states that many different types of arthritis, including certain cases of gonorrheal origin, are benefited. The arthritides in children, according to the same author, react favorably in contradistinction to those in the aged which do not respond well. In the treatment of arthritis, in general, benefit appears in the favorable cases usually between the 3rd and 8th week. Some cases do well when the treatment is interrupted for a few weeks and is begun again. Unfavorable symptoms, such as a permanent aggra- vation of the joint disorder or albuminuria, which have been alleged by some authors to have been caused by the radium have never been ob- served by Cudzent. 2. Gout. — Fait a, Cudzent and others have reported favorable results in the treatment of gout. The last named author states that of 86 cases who had exensive treatment (enuniatorium iiiludatioiis, ''drink cure"), 77 per cent to 89 per cent were improved and 9 per cent to 11 per cent unimproved. In the course of time, however, most of the patients ex- perienced recurrences. In a few patients no return of the disorder had taken place when the repoi-t was made. 3. Myalgia. — Benefit has been reported in some cases of the above disorders, the pain particularly being relieved according to many in- dividual repoi'ts (Faltii. (Judzent, Sommer, Kemen, Strasburger, etc.). Gudzent has never seen benefit, however, in neuralgia of the trigeminus. 320 RADIUM THERAPY 4. Hig'h Blood Pressure. — The reduction of hio-h ])lood pressure has been observed by many authors. Gudzent states that in some eases the ])lood pressure may be permanently reduced. Other authors, however, doubt the permanency of any reduction that may occur. Hayward Pinch has seen good effects from the use of radium emanation drinking water in angioneurotic edema. In arteriosclerosis, neuroses of the heart and myocarditis, benefit has been reported by some authors. In the last named diseases, tlie field for ]if)s;si])le error in the interpretation of results is, of eoiii'se, very great. 5. Chronic Inflammatory Processes. — Lachmaun states that he has seen fjood effects from the administration of radium in inflammatory disorders of the female pelvic organs. Several authors (Levy, etc.) have reported favorable results in the treatment of various disorders of the mouth, such as leukoplakia, pyorrhea, etc. 6. Bright's Disease and Diabetes. — Benefit has been reported by cer- tain authors in these disorders. 7. Pernicious Anemia. — Proescher recommends, on the basis of some excellent experimental studies, the intravenous injection of soluble ra- dium salts in pernicious anemia and other forms of anemia. Gudzent also has seen good results from the injection f)f thorium X in pernicious anemia, chlorosis, and secondary anemia. The favorable results in per- nicious anemia, are of course only temporary. According to Failla good results have been obtained by the injection of the active deposit in leu- kemia and Hodgkin's disease. The use of external radiations over the spleen is so satisfactory that there seems to be a small field, at present, for the use of radium internally in these disorders. The improvement in leukemia by any method of treatment is temporary although remissions may extend over consideralfle periods of time. 8. Dermatoses. — Individual reports of good effects in psoriasis and sclcrodci-ma have been made. 0. Malig'nant Disease. — Good effects have been re])orted by some authors fi-om llie administi-ation of radium in various forms of malignant disease. Failla has reported good results from the injection of the active deposit in lymphosarcoma. It seems to tiu^ wi-iter that for the present at least we must rely in mnlignant disease solely upon the effects of local radiations with radium i-alhei- than upon its constitutional effects when ingested or injected into the body. The radiosensitiveness of certain normal structures, such as the spleen, renders it unlikely that the internal administration of radium will ever be of practical utility in the treatment of most types of malignant disease. Long before the tumor itself will be unfavorably affected, noi-mal structures may be seriou.sly injured. The experimental work referred to above, i.e., the injection of active deposit, etc., is of course valuable from a scientific sta)uli)oint. RADIUM IN INTERNAL MEDICINE 321 In the field of internal medicine, the evidence seems to indicate that radium may be of benefit in (a) certain chronic joint disorders (notably rheumatoid arthritis and the joint disturbances of gout), (b) high blood pressure, (c) pernicious and other forms of anemia, (d) certain painful atfections, such as some forms of neuritis, which it sometimes seems to ameliorate. There is so much possibility of error in estimating the value of radium Avhen administered internally that many of the reports of benefit and cures must be accepted with the greatest caution until further experience has been accumulated. CHAPTER XXI PROFESSIONAL INJURIES DUE TO RADIUM Both local and constitutional injuries may be cansed by persistent exposure to radium rays. LOCAL EFFECTS "We have already described the acute inflammatory phenomena known as the "radium reaction" that may result from radium rays that are allowed to act with sufScient intensity on the skin. The various manipula- tions required in making; therapeutic applications render a certain amount of daily exposure to the rays almost unavoidable. As a result of these per- sistently repeated slight exposures, many workers suffer from a peculiar chronic dermatitis that affects especially the ends of the first two fingers and thumbs. The skin becomes roughened and loses its elasticity. Fis- sures and atrophic changes in the skin may develop. The nails become brittle and thin. Exaggerated longitudinal striation and splitting of the nails may occur. Tiny wartlike epithelial tumors may form on the flexor surfaces of the ends of the fingers and thumbs. These tumors vary in superficial extent from one millimeter to one-half centimeter or more and may project one or several millimeters above the level of the skin. They resemble a certain type of senile keratosis. They cannot be scraped off except with the greatest difficulty but when they are removed, a depression is left reaching nearly or quite to the corium. Even when removed thej' recur sooner or later and may persist for years becoming worse or better as the individual is more or less exposed to the rays. Fortunately there has not been observed as yet any tendency to the development of epitheliomata in connection witli radium keratoses. Sub- jectively the affected finger ends may sliow "anesthesia, paresthesia of varjMng degrees, tenderness, throbbing and even i)ain. The persistence of such effects is notowoi-thy." (Ordway.) CONSTITUTIONAL EFFECTS Those who are exposed more or less continuously to the gamma rays from radium may show various systemic symptoms, such as headaches, malaise, "nervousness," attacks of dizziness, menstrual disorders, etc. The most common of these symptoms is proba])ly a feeling of undue ex- haustion noted at the end of the day. In Avoiiien, menstrual disturbances may occur. At first menorrhagia may l)e pi-csent. The menstrual func- tion may then become irregular and amenorrhea may result. Normal 322 PROFESSTOXAL IX.ITTRIES DUE TO RA^I^^r 323 mensti'iiation i-etunis, liowever, Ml'tei- a sdiiicwliat proloiified absence from radium work. JMany workers in radium after a certain amount of ex- posure to the gamma rays develop definite blood changes. Gudzent and Halberstaedter examined twelve radium workers and found that blood changes were present in all. The effect on the white blood cells was shown 1)v a relative and absolute lymphocytosis, Avliich was ])resent in every case. In two cases, the hemoglobin was decreased but the number of red blood cells was apparently not affected. It is probable that the lymphocytosis mentioned above was an early effect of the rays, analogous to the initial lymphocytosis noted after therai)eutic injections of radium. Others who have studied the blood changes in radium workers have found that leukopenia is practically alwa^'s produced by persistent ex- posure to the gamma rays, Mottram and Clarke investigated the leu- cocytic blood-content of twenty laboratoiy and clinical workers engaged in handling considerable quantities of radium. The polymorphonuclear leucocytie and the lymphocytic blood content of all were found to be decidedly below normal. Tlie leukopenia manifested itself a few weeks after exposure. After a holiday of two months, the polymorphonuclear leucocyte and lymphocyte counts rose decidedly but fell again u]ion reexposure to the rays. Hayward-Pinch also found a leukopenia in radium workers. This author states that the total number of leucocytes may even fall as low as one thousaiuT per cubic millimeter. The hemo- globin and number of red blood cells in radium workers are not as mark- edly or as constantly affected as the Avhite blood cells. At first the hemo- globin may be slightly increased. Later it may be diminished. Sooner or later the number of erythrocytes is also decreased. No connection between the leukopenia and any condition of ill health, can, at present, be traced, althongh the possibility of untoward effects must be borne in mind. The oonstitutioiuil effects of the gamma rays can be minimized or obviated by a sufficient anunuit of care in haiulling the radium. For the protection of those engaged in radium work, various devices have been installed. To guard against the local effects of the rays we use (a) special forceps of different patterns. One type resembles the ordinai-y surgical tissue forceps, except 1liat llie radinm fdrct'iis are tAvelve inches long (Fig. 22). With these the radium tubes as well as the large radium pads can be conveniently grasped. Another type of foi-ceps lias thi-ce ])r(inys at one end, with which even the smallest tubes may be picked up ami held securely (Fig. 23). (b) Special "holders" for screwing together the dif- ferent parts of screens oi- other radium appaialns (Figs. 2') and 26). (e) A special instrument by means of which oiu' nuiy wi-ap up the radium tubes in dental rubber dam without handling them with the finL-'crs 324 RADIUM THERAPY (Fig. 24). All metal instruments used in handling radium apparatus should be covered with rubber tubing. Since using these devices the local untoward effects of the radium have not been observed. For guarding against the gamma rays which are the main cause of the constitutional effects we use (a) heavy lead "angle plates." These should be at least five centimeters thick and may be set in a table or shelf at Avhich the technicians may sit while manipulating the radium tubes. We have devised also a movable apparatus for the protection of the oper- ator. This consists of an upright heav}- cast iron plate attached to wheels. The apparatus can be easily moved about so as to stand between the radium applicator and the operator (Fig. 34). (b) Baskets lined with lead for transporting the radium pads from the making-up room to the patient. The baskets may be carried about by means of a sling. By this procedure the radium is constantly kept at some distance from the body and the gamma ray effect on the spleen and other important organs is minimized. In addition to these precautions we have found that it is imperative that radium workers should abstain from work for at least two days per week and should have frequent vacations of one or more months' duration. BIBLIOGRAPHY Ahhc, liohrrt : Exophthalmic Goitre Reiliui'd liv Kadiuin, Aivli. Kooiitg. Rav, 1904- ino.l, ix, 214-218. — Racliiini in Thoiapeutics, Boston Med. and Huiy;. Jour., I!)(t4, cl, Xo. 2, p. 53. — Action du radium sur (|uolquos tumours particulieros, Lo Radium, lOCl, ii, 3~)')7. — Radium in Surgery, .Jour. Am. Med. Assn., July 21, 1906, pp. lSr,-lS;j. — Ilhistratinfi the Penetrating: Power of Radium, Arch. Roentjr. Ray, 1907, xi, p. 247. — The Specific Action of Radium as a Unique Force in Therapeutics, Med. Rec, New York, 1907, Ixxii, p. ;>S9-594. — Radium in Surgery, Arch. Roontg. Ray, 1910, xiv, 277-281. — Radium as a Specific in Giant Cell Sarcoma, Med. 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No. 30, pp. 1192-1193. — Bescitigung dor durch Radiunistrahlon l)o\virktcn Gofassorweitorungcn, Miinchen. nied. AVchnschr., 1907, No. 38, p. 1877. — Kjilte und Uviolliohandlung in Verbin(hing mit Roiilgen und Radium, iEiinclion. med. Wclinschr., 191 fi. No. 4, p. 123. Ayrcs, Winficld: Radium in Cancer of the Bladder, New York Mod. Jour., Fobruarv 20, 1915, ci, 345-347. — The Effect of Intravenous Injections of Radium on a Persistent Positive Wasser- mann Reaction, Med. Rcc, New York, October 9, 1915, Ixxxviii, 610. Baeger: Ueber die physiologisclie Wirkung dor Bocquorolstrahlen, Ztschr. f. allg. Pliysiol., 1904, iv. Bagg, H. J.: Pathologic Changes Accompanying the Injection of an Active Deposit of Radium Emanation. Intravenous and Subcutaneous Injections in the White Rat, Jour. Cancer Rosoanh, January, 1920, pp. 1-24. Abstracted in Surg., Gynec, and Obst., May, 1920, xxx, 381. — The Response of tlie Animal Organism to Repeated Injection of an Active Deposit of Radium Emanation, Jour. Cancer Research, Octol)or, 1920, v. No. 4. — The Action of Buried Tubes of Radium Emanation upon Normal and Neoplastic Tissues, Am. Jour. Roentgenology, November, 1920, vii. No. 11, pp. 536-544. — The Effect of Radium Emanation on the Adult Mammalian Brain, Am. Jour. Roentgenology, So])tombor, 1921, viii, 536-547. Bagge, I.: Eine kom])iniorte l)iologisclic-radiologische Mothodo dor Cancerbehandlung, Ztschr. f. Krobforsch., 1910-11, x, 251-266. Bahr, F.: Zur Fragc dor kiinstlichon Erzougung von y-Strahlen radioaktivor Substanzou mittols Roentgonrohron, Strahlonthoraiiio, 1914, v. 427-430. Bailey, JJarold C: Radium in Utoriiio Cancer, Jour. Am. Med. Assn., July 14, 1917, Ixix, No. 2, p. 145. — and Bagg, H. J.: Radium Tlu'rapy in A'vdval and ^'aginal Cancer, Abstracted in Jour. Am. Med. Assn., 1921, p. ;'.14. — and — : \'ulval and Vaginal Cancer Treated l)y I'^iitorod and L'nfiltorod Radium Emanation, Am. Jour. Obst. and Gynec, December, 1921, ii. No. 6, 587. — , and Quintby, Editli: The Use of Radium in Cancer of the Female Generative Organs, Am. Jour. Obst. and Gynec, 1922, iii, 117-133. Baiscli, K.: Erfolge dor Mesothoriunibehandlung bei 100 Uteruskarzinomen, Miinchen. mod. Wchnsclir., 1915, No. 49, pp. 1670-1673. Balllia~ard, )'.; Ktudo physiologifpio et therapeutique dt's radiations emisos par les corps radioactifs et do lours omanatidns. Arch, d'oh'ctric med., 1906, xiv, 403-414. Bamford, E. K.: Use of Radium in Surgorv, .lour. Iowa Mod. Soc, M:iv, 1921, ix, 167. Bincat : Deux cas d 'epitheliomas cutanos gueris i)ar lo radium, !>ull. et mem. Soc med. d. hop. do I'aris, 1909, series 3, ])p. 931-935. — Traitement d 'uii iiao\us vasculairo plan ]iar lo radium, Prosso mod., 1909, No. 20, p. 174. — Vori'uos planes traitoos ]i:ir !»• r.nlinui, Bull. Soc. Irani; do dormat. et syph., T'aris, 1910, xxi, 172-171. — Die Kadiumthoraiiio in dor Dcrni.itnlnLiic, St i-.ilili'iitlii'rapio. I'.tll, i\-, 322-375. 328 RADIUM THERAPY — Die Eaclium thcrapic iiialigner Tiimoren, Stvahlentlierapie, 1914-1915, v, 51-69. — and Delamare, A.: Lc radium dans le traitemont des iievrolgics et des nevrites, Arch, d 'electric, med., 1908, xvi, 243-249. Barduszi, D.: Sul valore terapeutico della radio-attivita di alcime acque termominerali, ed in particolar niodo di quelle Sangiulianesi, Atti d. r. Accad. d. fisiocrit. in Siena, 1905, xvii, 601-604. Barringer, Benjamin, S.: Tlie Treatment by Radium of Carcinoma of the Prostate and Bladder, Jour. Am. Med. Assn., November 11, 1916, Ixvii, 1442-1445. — A Case of Carcinoma of the Prostate Controlled for Three and One-half Years by Radium, Internat. Jour. Surg., August, 1919, xxxii, 239. — Radium Treatment of Carcinoma of Bladder, Ann. Surg., December, 1921, Ixxiv, 751. — Carcinoma of Prostate, Surg., Gynec, and Obst., 1922, xxxiv, 168-176. Barrow, JF.: Treatment of Maliarnant Uterine Conditions with Radium, Kentucky Med. Jour., December, 1921, p. 770. Bartels, C. D.: Radiumbehandlingens Stilling i Udlan(let-Hosi>italiistid, Feljruary 23, 1921, pp. 117-127. Bashford, Mitrraii, and Bnicen: Third Scientific Report of Imperial Cancer Research Fund, 1908, pp. 276 and 298. — , — , and Cramer: Second Report Imperial Cancer Research Fund, 1905. Baud and MaJJot. L.: Universal Apparatus for Radium Therapy, Jour, de radio!, et d'electrol., June, 1921, v, 271. Baumm, Gustar : Yorlaufige Mitteilung iiber die therapeutische Verwendbarkeit des Mesothoriums. Berl. klin. Wchnsehr., 1911, xlviii, No. 35, p. 1594. Bayct, A.: Die Behandlung des Krebses mittels Radium, Strahlentherapie, iii, 473- 489. — Einige Einzelheiten iiber die Anwendung von Radium zwecks Bestrahlung, Radium in Biol. u. Heilk., 1912, i, 227-228. — Les effects therapeutiques du radium. Bull. Acad. roy. de med. de Belg., Brux., 1910, xxiv, series 4, pp. 459-516. — Le Traitement des nevrodemites par le radium, Jour. med. de Bruxelles, 1910, XV, 15-34. — Die Grenzen der Radiumthcrai>ie fiir den tiefliegenden Krebs nach dem heutigen Stande der Wissenschaft, Strahlentherapie, 1914-1915, v. 205-215. Bechold, H., and ZiegJcr, I.: Vorstudien iiber Gicht, Biochem. Ztschr., xx, 189; 1910, xxiv, 146. — ancl — ; Radium-Emanation und Gicht, Berl. klin. Wchnsclir., 1910, xlvii. No. 16, p. 712. Bcel; A.: Action des ravons du radium sur les ncrfs peripheriques, Bull. Internat. Acad. d. sc. de Craeovie, 1905, pp. 286-289. Beclc, Emil G.: Combined Surgical and Radium Treatment of Epithelioma of Lower Lip, Internat. Clinics, 1921, i, 31. — Denudation of Inoperable Cancer; an aid for Efficient Radio-therapy, Minnesota Med. Jour., June, 1921, iv, 360-370. — Radical Surgery as an Aid to Efficient Radiotlierapy in Apparently Hopeless Cases of Carcinoma. Internat. Clinics, 1921, ii, 46. Beclc, Joseph C: Further Report on the Use of Radium, the X-ray and Other Non- Surgical Measures, Combined with Ojjerations about the Head and Neck, Ann. Otol. Rhinol. and Laryngol.. June, 1921, xxx, 425-496. Beclton, TT., and Buss, S.: The Effect of Radium Emanation on Altmann's Granules, Arch. Middlesex Hospital. 1911, xxiii, 52-55. Beclere, A.: Le dosage en radiotlierapie. La Presse med., 1904, i>p. 75-78. — Note sur I'emploi tlierapeuti(|ue des sels de radium, Bull, et mem. Soe. med. d. hop. de Paris, 1904, xxi, series 3, 1202-1215. — Nouveau procede de Radium, Semaine med., 1911, No. 20, p. 235. — L'ionometre radiologique du Dr. Solomon, Bull. acad. d. med., Paris, July 5, 1921, Ixxxvi, 3-5. — and Beelerc, Jlcnri: Die radiotlierapeutisclie lUliandlung der Lcukamie, Strahlen- therapie, 1913, iii, 553-560. Bccquerel, Henri: Sur diverscs proprietes des rayons uraniques, Compt. rend. Acad. d. sc., 1896, cxxiii, 855. — Sur le rayonnement de I'uraiiium, Compt. rend. Acid. d. sc, 19()(t, cxxxi, 137. — Sur la lumiere emise spontanement par certains sels d "uranium, Compt. rend. Acad. d. sc, 1904, cxxxviii, 184. p.ini.KHiHAi-iiv 329 Becqucrd, Taul: Ri'du-rclio siir l;i ladidiutivife vej,a''taK', Coiinit. rend. Acad. d. sc, 1905, cxl, 54. — Iiifluonee dcs scls d 'iiianiuiu ot de tlioiiiini siiv Ic deveddiipt'iiioiit du bacillc dc la tubcreulose, Somaine med., 1913, No. 4, p. 4.j. Begouin: Zwei Fiille von Lvinpliosarkom dcs Halses, Straldonthcraijio, 1914-191.J, v, 651-654. — Radium Treatniont of Utfrino Cancer, Gynec. ft Obst., Paris, 1921, Iv, 410. Bcirne, II. P.: Physics and tlic Use of Eadiiiin, Illiiuiis Mod. Jour., ^^a^cll, 1021, xxxix, 201.' Bclot, J.: La valour do la radiothorapio, Paris mod., 1917, xxi, 445-450. Be^nczur, Julius r.: Uebor oinen iiacli Gobrauch einor Radium omanationskur wosenf- lieli gcbossorton Fall von Sklorodorniic, Doutsdi. med. Wcliiisclir.. 1911, xxxvii. No. 22, pp. 1029-10.10. — Ueber Heilerfolg^e mit RadiunK'niaiiationskurfii, P>crl. kiln. Wclinsdir., 1912, xlix, No. 3, pp. lOS-109. licncdiM, TV.: Zur Prage dor Anwondunsj grosser odor kloinor Doscn von Radinm- cmanation, Med. Klin., 1912, viii, 143-145. Benjamin, E., Ecuss, A., Slnila, E., and Schwari:::, G.: Boitrafje zur Fragc der Ein- wirkunp^ der Rontjjenstralilon auf das Blut, Wien. klin. Welinsclir., 1906, pp. 788-794. Bcnncwitz : Messmofliodon dor Radioaktivitat und iliro Anwondiuifj in dor Raar la flamme de Toxyde de carbone et par les rayons du ra. 495-498. Butcher, W. Deanc: .The Action of Radium on Malignant Neoplasms, Arch. Roentg. Rays, 1906, xi, 156-159. — The Therapeutic Action of Radiuui, Fortsclir. a. d. Geb. d. Rontgenstrahlen, 1909- 1910. xiv, 70. Butler, J. IV., Tf'illiamson, C. S., and Brown, U. 0.: Effects of Radium on Normal B^rain Tissue, Surg., Gynec, and Ohst., 1920, xxi, 239. Butler, T. ITarrison : Some Remarks upon Sjiring Catarrh, witli Special Reference to Its Diagnosis and Its 'rrcnlniciil witli Hadium, Brit. Jour. Ophthal., 1917, i, 411-415. p.ibf,io(;rai*hy 333 Builin., Henry: On Radiiim in the Treatment of Cancer and Sonic Associated Con- ditions, Laneet, London, liXHt, elxxvii, 1411-1411. Buxhcmm, B.: Znr Tliera]iie von Xouralgion niit Radium. Zts<-l;r. f. j>hys. u. diiitet. Therap., 1012, xvi, 257-261. Caan, Albert: Ucbcr Radiumbehaiullung dor bosartigcn Goscliwiilstc, ^Fiinf-hen. mod. Wchnsclir., 1900, No. 42, pp. 2147-2149. — Uober Radiumwirkung auf maligne Tumoron, Ei'itr. z. klin. Cliir., 1009, Ixv, 773-829. — Uebor die Fiihigkeit nienschlic-hor Organc, die Luft fiir Klektrizitiit loitond /ii niaehen, (Radioakt ivitiit), Miinclien. mod. "Wdinscdir., 1011, Xo. 21, ]>\k 1 12()- 1127. — Uebor Radioaktivitiit monscdilielier Organe. Ileideb., 1011, O. Winter. — (111(1 liam-'^(nier, C: Uebor Radiumansschiodnng im Urin, ^Fiintdien. mod. Wdinsclir., 1010, No. 27, pp. 1445-1448. — and Werner, J?,: Elecktro- und Radioehirnrgio. im Diensto der P.oliandhing nialigner Tumoren, Miincdien. mod. Welinsehr., 1011, No. 23, pp. 1225-1230. Cdldbrese, A.: SuU'azione del Radio sul virus rabbico, Riforma mod., 1006, pp. 34-39. — Sur le Traitemont de la rage i)ar lo Radium, Ann. d. I'lnst., Pasteur, 1907, pp. 156-160, 480-493, 496. Cameron, A. T.: Recent Work on the Transmutation of Klements, Part I, Radium, June, 1913, i, No. 3, pp. 3-7. — Recent Work on the Transmutation of Elements, Part II, Radium, July, 1913, i, No. 4, pp. 3-6. Cameron, William. H.: Radium Emanation Therapy in Arthritis Deformans, Radium, August, 1913, i, No. 5, pp. 3-5. — The Treatment of Alveolar Pyorrhea with Radium Emanation, A Review, Radium, December, 1013, ii. No. 3, pp. 41-43. — Radium in the Treatment of Cancer, Radium, December, 1014, iv. No. 3, pp. 37-56. — Radium in Military Surgery, Pennsylvania Med. Jour., :N[arch, 1916, xix. No. 6, pp. 449-453. — Radium in French .Nfilitary Surgery, Pennsylvania Mod. Jour., Soptoinbor, 1016, xix, 906-908. — Radium in War Surgery, Pennsylvania Med. Jour., June, 1018, xxi, 579-580. — and Viol, Charles H.: Classification of the Various Methods Employed in the Internal Administration of Radium Emanation and Radium Salts, Radium, January, 1015, iv, No. 4, pp. 57-68. Cary, E. E.: Use of Radium in Epithelioma of Lateral Wall of Nose. Texas State Jour. Med., April, 1021, xvi, No. 12, p. 536. Case, J. T.: Comparison of the Operative and Radiothorapeutic Treatment of Uter- ine Myomas, Surg. Clinic, Chicago, 1017, i, 570-593. Caspari, W.: Die Bedeutung des Radiums und der Radiumstrahlon fiir die ^redi/in, ' Ztschr. f. Diatot, u. pliysik. Tlierap., 1905, viii, 37-45. Cltadwicl:, J.: The Excitation of Gamma Rays by Alpha Rays, Philosni>liical Mag., 1913, XXV, 103-lil7. Ch(ihipecl-}i, H.: Uebor die Wlrkung verschiedener Slrahlungen auf das Augo, StrahU-n- tiierapie, 1017-1018, viii, 141-154. ^ Chamlxrs, Helen, and Russ, S.: Action of Radiations upon Some of the ^lain lon- stituents of Normal Blood, Proc. Roy. Soc, 1911, Ixxxiv, Series B, pp. 124- 136. f 1 r 1 — and — The Bactericidal Action of Radium Emanation, Proc. Roy. Soc. Med., 1 atli., Sec, 1912, V, 198-212. __ „„(i _ 0,1 the Action of Radium Rays upon the Cells of Jensen s Rat Sarcoma, Arch. Middlesex Hospital, London, 1913, xxx, 120-134. Clias<; Carroll: Remarks on the Dosage of Radium and the Form and NbMlu.d ot its Apidication, Und. and Cutan., Rev., 1022, xxvi. 1 I Ki. Chase, Walter B.: A Conservative Estimate of Radium Therapy from the Clinical Standpoint, New York Med. Jour., January 9, 1015, yy. 63-67. — Radium in Gvnecological Practice, Am. Jour. Obst., 1015, Ixxii, 90-97. — Radium in Nonnmlignant Conditions, Long Island Mod. J(Uir., Decem])or, 101. .. pp. 508-510. , , ,, . ,,11 Cheron, 77.: De la Radiumthera|'io des Fibromos Pterins, Jmir. do mod. do 1 ans, l.Hl, No. 49. pp. 953-!t57. 334 RADIUM THERAPY — and Jlubens-Duval, H,: Aperqu sur les resultats de la radiumtherapie des cancers de 1 'uterus ct du vaftiii, Bull. Soe. d'obst. ct de Gynee. de Paris, 1913, xvi, 418-429. — and — Ucber deu Wert der Eadiumtherapie in dcr Behandlung der uterinen und vaginalen Krebse, Fortsclir. a. d. Geb. d. Rontgentralilen, 1913, xxi, 229-238. — and — Der AVert der Radiunibeliandluug des Gebarmutter- und Seheidenkrebses, Strahlentherapie, 1914-1915, v, 80-91. Chesney, L. M.: Use of Thorium and Eadium in Some Diseases of the Pharynx and Larynx, Practitioner, London, 1909, Ixxxiii, 233-237. Chevrier, L.: Traitement preventif par le radium des recidives des epitheliomas mu- queux et glandulaires apres extirpation chirurgicale, Arch, d 'electric, med., 1910, p. 328. — Traitement du rhumatisme blennorragique par les injections intra-articulaires on peri-artieulaires de sels insolubles de radium, Gaz. d. hop., Paris, 1910, Ixxxiii, 807-810. Christen, T. : Energiemessung von ionisierenden Strahlen insliesondere von Rontgen- strahlen, Physik, Ztschr., 1916, xvii, 23-25. Chuiton, and Auhine.au: Sucees de la Radiotherapie et de la Radium therapy dans wn cas "Maladie do Mikulicz." Arch, d 'electric, med., 1912, No. 333, pp. 406-410. Clntrchward, A.: Treatment of Rodent Ulcer by Calcio-Phosphate of Uranium, Lancet, London, 1911, clxxx, 660. ClaijeU, A. N.: Radiumtherapy of Thyroid, Jour, of Radiol., 1920, i, 121-124. — The Treatment of Goiter with Radium, Illinois Med. Jour., October, 1920, xxxviii, 318-319. Clap, Ednvund W. : Progress in Ophthalmology, Boston Med. and Surg. Jour., January 7, 1915, clxxii. No. 1, pp. 22-23. ClarL; A. Schuyler: Radium Treatment of Cutaneous Epitheliomas by Single or Mas- sive Doses, Jour. Am. Med. A.ssn., 1914, Ixii, 1453-1458. Clarl:, John G.: "What do the Newer Methods of Treatment Offer the Patient with Malignant Disease of the Uteriis, New York Med. Jour., September 4, 1915, cii, 485-487. — Results Obtained bv the Use of Radium in the Treatment of Cancer of the Uterus, Ann. Surg., 1916, Ixiv, 602-612. — Radium Therapv in Uterine Hemorrhage of Benign Origin, Jour. Am. Med. Assn., July 14, 1917, Ixix, No. 2, p. 145. — The Treatment of Myoma Uteri with Radium, Jour. Am. Med. Assn., 1919, Ixxiii, 957-961. — The Relative Values of Radium and Surgery in the Treatment of Tumors of the Pelvic Organs, Ann. Surg., 1920, Ixxi, 683-696. — and Keene, Floyd E.: Radiation in Inoperable Cases of Carcinoma in the Female Genito-Urinary Organs, Am. Jour. Roentgenology, January, 1920, vii, 36-41. ■ — and — Irradiation in Cancer of Female Genito-Urinary Organs, Results in 313 Cases, Jour. Am. Med. Assn., 1921, p. 613. Clarl-, J. J.: Combined Use of Roentgen Ray and Radium in Treatment of Malignant Disease, Georgia Med. Assn. .Jour., December, 1921, x, 839. Clarl-, S. M. D.: Use of Radium in Fifty Cases of Uterine Hemorrhage from Causes other than Carcinoma or Myoma, .Tour. Am. Med. Assn., September 27, 1919, Ixxiii, 952. Clarl-, IVilliam L.: New Conceptions Relative to the Treatment of Malignant Disease with Special Reference to Radium in Needles, Pennsylvania Med. Jour., Jan- uary, 1921, xxiv, 214-224. Cleaves, Margaret A.: Radium with a Preliminary Note on Radium-rays in the Treat- ment of Cancer, Med. Rec, New York,' October 17, 1903, Ixiv, 601-606. Cohen, Martin, and Levin^ Isaac: The Action of Radium on Cataract, New York Med. Jour., July 6, 1918, cviii, 4-5. — and — The Action of Radium on Cataracts, Jour. Am. Med. Assn., October 18, 1919, l.xxiii, 1] 93-1200. Cohn, Hermann: Die Heilung des Trachoms durdi Radium, Bcrl. kliii. Wclmschr., 1905, xlii, 22. — Wcitere Bemerkungen iiber Behandlung des Trachoms niit Radium, Berl. kliu. Wchnschr., 1905, xlii, 222. Cohn, S.: Die Bedeutung des Natriums und Kaliums fiir die Eiitstelumg und Heilung der Gicht, mit Beriicksichtigung des Radiums, P.erl. kliu. Wchnschr., 1912, No. 12, pp. 545-549. RIRLTOGRAPHY 335 Colwell and Hii/ifi: Radium, X-rays and tlic Liviuij fell, London, 1!)1."), J. Boll and Sons. Condamin., E.: Radium Treatment of Uterine Cancer, Lvon Med., August 25, 1021, cxxx, 719. Condon, A. P., and Newell, C. H.: Report of Two Years' Use of Radium at the Nich- olas Senn Hospital, Omaha, Nebraska, Radium, Decenilier, lOlS), xiv, No. 3, pp. 49-55. Contamin: Conipt. rend. Acad. d. sc, 1910, el, 1537. — Le Cancer experimental, Paris, 1910, Masson. Corscaden, James Albert: The Rationale of Radiothera])v in Uterine IIeniorrhai;e, Am. Jour. Obst., 1918, Ixxvii, 250-272. CourmeUcs, Foveau de: Die Rontgen und Radiumstralilcn in der t^vniikologie, Stralden- therapie, 191.3, iii, 388-407. Canrtin and Bereionie: Epithelioma lingual et radium, Caz. lielid. d. sc. med. de Bor- deaux, i904, XXV, 18. Cramer: Action of Radium on Tra.ns])lanted Mouse Tumours and Its Relation to the Spontaneous Arrest of Their Growth, Imi)erial Cancer Research Fund, Part II, 1905, pp. 56-68. Cramer, W., Drew, A. IT., and Moitran, J. E.: Similarity of Effect Produced by Ab- sence of Vitamins and by Exposure to Roentgen Rays and Radium, Lancet, London, May 7, 1921, i, 9G3. Cremieu, V.: Salles d 'inhalation : oabines et appareils de mesure i)our 1 'emploi thera- pcutique de 1 'emanation du radium, Arch, d 'electric, med., 1913, xxiii, 117- 129. Croclcer, H. BadcUffe: The Therapeutic Effects of Radium-emanations in Some Diseases of the Skin, Lancet, London, 1909, clxxvi, 1447-1448. Cvoolces, Sir liViUiam: Radioactivity of Uranium, Proc. Rov. Soc, Loinlon, 1900, Ixvi, 409-423. Crossen, H. S. : Tlie Choice betAveen Radium, X-Ray and the Knife in the Treatment of Uterine Myoma and Uterine Cancer, Jour. Mo. State Med. Assn., Febru- ary, 1922, xix, 55. Crouzon, 0., and Folley: Radiotherapie du goitre exoplithalmique, P>ull. et mem. Soc. med. d. hop. de Paris, 1912, xxxiv. Series 3, pp. 690-693. Cullen, Thomas S.: America's Place in the Surgery of the World, Surg., Gynec, and Obst., 1917, XXV, 376-390. Culver, George D.: In Reference to the Behavior of Radium in Cancer of the Lip, Urol, and Cutan., Rev., 1922, xxvi, 16-19. Curie, Marie Sklodowsla : Rocherches sur les substances radioactives, ed. 2. Paris, 1904, Gauthier-Yillars. — Traite de radioactivite, Paris, 1910, Gauthier-Yillars. — Die Entdeckung des Radiums, Leipzig, Akadernische Yerlagsgensellschraft, 1912. — and Dehierne, A.: Sur le radium Metallique, Conqit. rend. Acad. d. sc, 1910, cli, 523-525. Curie, P.: Conductibilite des dielcctriques liquides sous rinlluence des rayons du radium et des rayons de Rf)ntgen, Compt. rend. Acad. d. sc, 1902, cxxxiv, 420-423. — and Becquerel, Ilcnri: Action physiologique des rayons du radium, Compt. rend. Acad. d. sc, 1901, cxxxii, 1289-1291. — and Curie, Marie Sklodoirsl-a : Sur une substance nonvelle radio-active, contenue dans la pechblende, Compt. rend. Acad. d. sc, 1898, cxxvii, 175-178. — and — Sur les corps radioactifs, Conqit. rend. Acad. d. sc, 1902, cxxxiv, S5-87. — — and Bemont, G.: Sur une nouvelle substance fortement radioactive, contenue dan» la pechblende, Compt. rend. Acad. d. sc, 1898, cxxvii, 1215-1217. — and Dehierne, A.: Sur la radioactivite induite et les gaz actives ]>iir le radium, Compt. rend. Acad. d. sc, 1901, cxxxii, 768-770. — and Lahorde, A.: Sur la chaleur dogagee spo?itaiu''ment par les sols de radium, Compt. rend. Acad. d. sc, 1903, cxxxvi, 673-675. — and — Sur la radioactivite des gaz qui se degagent de I'oau des sources fliermalcs. Compt. rend. Acad. d. sc, 1904, cxxxviii, 1150-1153. Currupi, C: Experimentelle Untersuchungen iiber das Verlialten der Radioaktivitiit der Dorner Mineralquellen, Ztschr. f. Balneol., Klimat, etc., 1910-1911, iii. 441, Czcrny, Tincens: L 'action du radium sur les tissus vivants, Cong. Fraiu'. de chir., 1904, pp. 236-237. — Bemerkungen iiber die lujektion von Radiumjiraparaten bei malignen Tunmren, Deutsch. med. Wcinischr., 1909, No. 51, p. 2252. 336 RADII'M THERAPY — Ueber den Gebraiich der Fulouration uiid der Kreuziiaelier Radiopraparate bei der Behaiidlung des Krebse, Arcli. f. klin. Cliir., 1909, xc, 137-152. — Zur Eroffimug- der II, inteinat. Konfeieuz fiir Krebsforselumg in Paris, Miiuehen. med. Wchnschr., 1910. Xo. 44, pp. 2305-2307. — and Caan, A.: Ueber die Behandlung bosartiger Geschwiilste mit radioaktiven Sub- stanzen, speziell mit Aktiniom, Miinelien. med. Wchnschr., 1911, No. 34, pp. 1801-1802. — - and — Ueber die Beliandhnig Ixisartiger Geschwiilste mit Mesothorium und Thor- ium X, Miinchen. med. Wchnschr., 1912, Xo. 14, pp. 737-742. Czrellitzer: Beequerelstrahlcn nnd Blindheit, Berl. klin. Wchnschr., 1903, xl, Xo. 28, p. 650. D Jkicosta, A. F. Jr.: Radium Treatment of Cancers, Brazil-med., February 5, 1921, XXV, Xo. 5, p. 73. — Radium Treatment of Cancers, Brazil-med., February 19, 1921, xxv, Xo. 8, p. 98. Dads, F.: Eadium Therapeutic Drainage. Gvneeologie et Obstetrique, Paris, 1921, iv, 459. Danne: Sur uu nouveau mineral radifere, Compt. rend. Acad. d. sc, 1905, cxl, 241. Danyss, Jean: De 1 'action pathogone des rayons, et des emanations emis par le radium sur differents tissus et different* organismes, Compt. rend. Acad. d. sc, 1903, cxxxvi, 461-464. — De 1 'action du radivmi sur les differents tissus, Compt. rend. Acad. d. sc, 1903, cxxxvii, 1296-1298. — De Taction du radium sur le virus rabique, Ann. de I'Inst. Pasteur, 1906, xx, 206- 208. — Sur le ralentissement subi par les ravons B lorsqu 'ils traversent la matiere, Compt. rend. Acad. d. sc, 1912, cliv, 1502-1504. Darier, M.: Action analgesiante du radium, Semaine med., 1903, Xo. 40, p. 330. — Application therapeutique du radium dans quelques affections nerveuses, Semaine med., 1904, p. 51. — , Valade, and Terson-: Traitement de I'cijithelioma par le radium, Presse med., 1905, Xo. 54, pp. 430-431. Barms, H.: Ueber Radium und seinen Einflusz auf die Korpertemperatur des Menschen, Inaug.-Diss., Berlin, 1911. Darwm, C. G.: The Stmcture of the Atom. Xature, 1920-1921, cvi, 51-54, 81-83, 116- 118. DrnipMn, J.: Influence des rayons du radium sur le developpement^ et la croissance des champignons inferieurs, Compt. rend. Acad. d. sc, 1904, cxxxviii, p. 154. Bantwiiz, Fritz: Beitrag zur biologischen Wirkung der radioaktiven uranpecherziiek- stande aus St. Joachimsthal in Boehmen, Ztschr., f. Heilk., 1906, Abt. fiir Interne Med., pp. 81-96. — Ueber St. Joachimsthaler Radiumtrjiger, Wien. klin. Wchnschr., 1911, Xo. 22, pp. 775-777, 1912, Xo. 3, pp. 119-122. David, Oslcar : Emanationsapparat mit genauer Dosierung, Radium in Biol. u. Heilk., 1913, ii, 345-352. Davidsolm, Felix: Radiumcmanation als Heilfaktor, Deutsch. med. Wchnschr., 1908, Xo. 38, pp. 1633-1635. Davidson, Mackenzie, James, and TMWson, Arnold: A Case of Spring Catarrh Treated and Cured bv Radium, Tr. Oplitlial. Hoc. of the United Kingdom, 1909, xxix, 239-245. Davison, J. M.: Radium and Some of Its Physical and Therapeutic Properties, Bris- tol Med.-Chir. Jour., March, 1910, xxviii, 1-16. Dcavcr, John B.: Hysterectomy at the Lankenau (formerly the German) Hospital, Ann. Surg., "l921, Ixxiii, 84-90. Dchiernc, A.: Sur nne nouvelle matiere radio-active, Comjit. rend. Acad. d. sc, 1S99, cxxix, 593. — Sur un nouvel element radio-actif: 1 'actinium, Compt. rend. Acad. d. sc, 1900, cxxx, 906. — Sur la decomposition de I'enu par les sels de radium, Compt. rend Acad. d. sc,- 1909, cxlviii, 703. Dehove: Un cas d'arfhrite blennorragique suppuree traitee et guerio par le radium, Jour. med. fran^., Paris, 1910, iv, 248-252. DeiTos.trs, P.: Le Radium en therapeutique. Piesso med., 1905, Xo. 16, pp. 121-122. Bini.IOGRAPHY 337 Degrais, P.: Radiumbehamllunj^ dos Rliinophymas, Stiahleiitherapie, 1913, iii, 86-88. — Cancer of the Cervix, Arch. Mens. d'Obste. et de Gynec, Paris, November, 191!), viii, No. 11. — Radium Treatment of Vulvar Veg:etations, Gyiiec. ct Obst., I'ltris. litlM, iv, 49:5. — and Bellot, Amclme: Uteruskrebs uiid Kadium. Str;il:lfMt]icra|iie, 1914-191.J, v, 1()12- 116. — and Pasicau: Die Behandlung- der Prostatatuuiorcu durdi das Radium, 8trahlen- therapie, 191.3, iii, 5-42-545. Deland, E. M.: The A B C of Radiuui. P.ostoa M,'d. and Sin-, .b.ur.. June .".n, liii'l, clxxxiv. No. 26, pp. 696-702. Delano, Samuel: A Study in the Internal Therapeutics of Radium, ^^ed. Rec, New- York, 1915, Ixxx'viii, 137-14:5. Delavan, D. Bryson: The Effects of Radioactivity upon Nasoiduiryngeal Fibroma, Med. Rec, New York, June 26, 1915, Ixxxvii, 1056-1058. — Radium in the Field of La ryn oology, Med. Rec, New \wV., July 8, 1916, xe, 50-52. Delhet, Pierre, Ilerrenschmidt, A., and Mocquot, P.: Action du radium sur Testomae, Bull, de I'Assoc, fran?. 1 'etude du Cancer, 1909, ii, 103-119. Demargay, Eug.: Sur le spectre d'une substance radio-active, ('(impt. rend. Acad. d. se., 1898, cxxvii, 1218. — Sur le spectre du radium, Compt. rend. Acad. d. sc, 1899, cxxix, 716-717. — Sur le spectre du radium, Compt. rend. Acad. d. sc, 1900, exxxi, 258-259. Deming, Clyde L.: Results in One Hundred Cases of Cancer of Prostate and Seminal Vesicles Treated ^A•ith Radium, Surg. Gynec. and Obst., 1922, xxxiv, 99-118. Descomps, P.: Radium Treatment of Uterus Fibromas, ^Mediciiu-, Paris, April, 1921, ii, 554-559. Desnos, E.: Action du radium sur les hypertrophies prostatiques, Bull, med., 1909, xxiii, 1088-1089. — Traitement de 1 'hypertrophic et du cancer de la ]u-(istate par le radium. Bull, med., 1914, xxviii, 231-233. Dessaiier, Friedr.: Die physikalischen unci technischen Grundlagen bei der Radium- liestrahlung und der Rontgenljestrahlung und die wichtigsten Fehler, Strahlen- therapie, 1914, iv, 452-463. ■ — Radium, Mesothorium und harte X-Strahlung, Leipzig, Nemnich, 1914. Deutmami, L.: Radium und Stoffwechsel, Muenchen, 1910, O. Gmclin. Deutschmann, D. E.: Ueber intraokularen Tunmr und Strahlentherapie, Ztschr. f. Augenh., 1915, xxxiii, 206-209. Dewar, Sir James: Sur I'emploi du radiometre pour 1 'observation des basses prcs- sions dans les gaz; application a la recherche des produits gazeux emis par les corps radioactifs, Compt. rend. Acad. d. sc, 1907, cxlv, 110. Dickinson, B. M.: Malignant Disease of the Throat, Pennsylvania Med. Jour., July, 1918, xxi, 611-613. Dieffenhach, William H.: Radium in the Treatment of Cam-er, Med. Rec, New Yiu-k, 1913, Ixxxiv, 1068-1072. — Reports on Cancer Patients Treated with Roentgen or iridium Hays Hemainin>+ Clinically Cured after More tiiaii Three Years, Jour. Am. Inst. Hom.eoii., 1916- 1917, ix, 430-436. Dinger: Beitrag zur Behandlung des Trac]u)m.s mit ll;idium, P.erl. kliii. Wdinschr., 1906, No. 40, 1311-1313. Dixon, H. n., and Wigham, J. T.: A Note on the Action of Radium on Some Organ- isms, Dul)Iin Jour. Med. Sc, 1904, cxvii, 161-164. Doderlein, A.: Strahlentherapie bei Carzinom, ]5eitr. z. Chir., xcv, 584-592. — Zur Strahlenbehandlung des Krebses, Zentralbl. f. Gyniik, 1915, No. 12, i)p. 185-189. and Seuffert, von: Unsere weiteren Krfahrungen mit . 49::-495. 338 RADIUM THERAPY — Du traitement dcs tiimeiirs iiialignes par le rayoiinement ultra-penetraiit du radium, Bull, de I'Assn. franc, du cancer, December 21, 1908, pp. 124-156. — Ueber Radiumbeliandluug, tiefliegender, inoperabler careiuome, Berl. klin. Wclnisehr., 1909, No. 31, p. 1471. — Physique niedicale du radium traitement des cancers par le radium. Arch. gen. d. med., 1909, pp. 404-482. — Des sels de Eadium insolubles en therapeutique, Presse med., 1910, No. 22, p. 186-187. — Traitement des tumeurs malignes par le radium, Gaz. d. hop., 1910, Lsxxiii, 126.J- 1268. — Die Rezeptivataet der nornialen und pathologischen Gewebe fiir die Radium- strahlung, Strahlentherapie, 191.3, iii, 379-387. — and Barcat : Sur le processus histologique de la regression des tumeurs malignes sous 1 'influence du rayonnement du radium, Compt. rend. Soe. de biol. 1908, Lxiv, 1052-1054. — , — , and Beaudoin: Comparaison des rayons de 1 "ampoule de Crookes et des rayons du radium au point de vue therapeutique, Arch, d 'electric, med. Bordeaux, 1911, xix, 113-120. — and Bovy: Epithelioma de la levre inferieure traite par les rayons gamma du ra- dium, Presse med., 1908, p. 165. — and Clieron: Ueber Badiumbehandlung tiefliegender Krebse, Zentralbl. f. Eont- genk., 1910, p. 169. — , — , and Barharin: Guerison d'un Hemo-Lymphangiome profond des regions cerv- ieale et sus claviculaire gauches par le radium, Bull, et mem. Soc. med. de hop. de Pari's, 1910, xxix, 556-560. — and Faure-Beaulieu, M.: Repression d'un Sarcome de la gencive par 1 'evolution Fi- 1)romateuse sous 1 "influence du rayouriemcnt ultra penetrant du Radium, Presse med. 1909, xvii, 77-79. — and — Arret et sejour prolonge du sulfate de radium dans les tissus vivauts, pen- dant une duree excedant une annee, Compt. rend. Soe. de biol., 1910, Lxviii, 46-48. — Harct, P., and Jaboiii, A.: Sur les modifications des tissus consecutives a I'introduc- tion du radium par electrolyse dans I'organisme vivant, Compt. rend. Soc. de biol., 1911, Ixx, 431-432. — LaJjorde, A., and Laborde, Mine. A.: De la Fixation, par le squelette, au radiiun injecte a I'etat soluble, Compt. rend. Soc. de biol., 1913, Ixxv, 108-110. — and Martel, de : Radiumtherapie du cancer de la langae, Presse med., 1910, No. 18, p. 155. — , Petit, G., and Jahoin, A.: Sur le radioactivite persistante de Torganisme resultant de 1 'injection intraveineuse d'un sel de radium insoluble et sur ses applica- tions, Compt. rend. Acad. d. sc, 1910, cl, 726. — , — , and — Radioactivite persistante de I'organisme sous 1 'influence des injections du radium insoluble. Serotherapic radioactive, Comp. rend. Acad. d. sc, 1911, cliii, 1509. — and Bitbens, DuvaJ: Sur le processus Histologicpie de la Destruction des Cellules Epithelioma tenses, par le Rayonnement Ultra-Penetrant du Radium, Bull. et. mem. Soe. med. d. hop., 1909,^xxviii, 274-280. — and Warden, A. A.: The Technique and Results of Radium Therapy in Malignant Disease, Brit. Med. Jour., August 27, 1910, pp. 516-518. Dreycr, Albert: Radium als Kosmetikum, 1913, Frieilrich Cohen, Bonn. Duane, Wm.: Methods of Preparing and Using Radioactive Sul)stances in the Treatment of Malignant Disease and of Estimating Suitable Dosages, Boston Med. and Surg. Jour., December 6, 1917, clxxvii, 787-799. — and Greenourjh, Jiobcrt B.: Report of Results of Radium Treatment at the Collis P. Huntington Memorial Hospital by the Cancer Commission of Harvard Uni- versity, Boston Med. and Surg. Jour., Septenilier 13, 1917, clxxvii, 359-365. DnCasse, B. B.: Radium and Hvpertrichosis, Observations and Technic, Radium, Sep- tember, 1920, XV, 101-103. 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T. : Radium Emanation in Upper Air Passages as Compared to Radium ; a Method of Applying with Especial Reference to Laryngeal Carcinoma, Illinois Med. Jour., August, 1921, xl, 85-91. Freudoithal, Wolff A.: A Case of Leukoplakia Treated bv Radium, Arch. Physiol. Therapy, "1906, iv, 7-9. — Experiences with Radium in Diseases of the Throat and Nose, Jour. Advanc. Therap., 1906, xxiv, 279-287. — Ueber die Behandlung maligner Tumoren der oberen Luftwcge mittelst Radium, Arch. f. Laryngol. u. Rhinol., 1911, xxv, 3-8. Freund, Ernst, and Kamincr, Gisa: Uel)er chemische "Wirkungen von Rontgen- und Gelenkkrankheiten mit Mesothorschlamm, Therap. Monatsh., 1913, xxvii, 282- 6, pp. 201-203. — and Kriser, Arthur: Ueber die Behaudhing dor Ischias, Tabes und chronischen Gelenkkrankheiten mit Mesothorschlamm, Tlierap. Monatsh., 1913, xxvii, 282- 284. Freund, Priil, 191. '^i, i, No. 1, pp. 13-14. Futli, II., and Ebcler, F.: Rontgen-uiul Radiumtliorapie des Uteruskarzinoms, Zcntralbl. f. Gyniik., 1915, No. U, pp. 217-227. G Ciihicyler, M.: Experinienteller B-eitrag zur cliemiselien Wirkung der Rontgentrahlcn, Fortschr. a. d. Geb. d. Rontgenstrahlen, 1917, xxv, No. 1, pp. 41-53. Guleicsly : Ueber die Heilung der plastischen Induration des Penis mit Radium, Der- mat. Wclinschr., 1916, Ixiii, 779-783. GoAiUier, Bene, and Labcy, Georges: Essai de traitement. d'un neoplasme du pylore par 1 'application du radium sur la tumeur grace a une fistula gastrique per- nianente, Gaz. d. hop. de Paris, 1910, Ixxxiii, No. 16, pp. 211-216. Gauss, C. J.: Weitere Fortsc'hritte auf dem Geliiete der gj'uiikologischen Radiotlier- apie, Strahlentherapie, 1912, i, 132-137. — Gyuakologische Tiefentherapie, Strahlentherapie, 1913, ii, 623-641. — Zur Technik der gynakologischen Mcsothoriumtherapie, Strahlentherapie, 1913, iii, 348-364. — Ueber die Priuzipien der Strahlenbehandlung gutartiger und bosartiger Ge- schwiilste, Strahlentherapie, 1914-1915, v, 379-400. — and Krinslci, B.: Die Mesothoriumbehandlung der Myome und iletropathien, Strah- lentherapie, 1914, iv, 440-451. — and Lemcke, H.: Rontgentiefentherapie, Wien., 1912, Urban and Schwa rzenberg. Gebelc: Zur Strahlentherapie der malignen Tumoren, Beitr. z. klin. Chir., xcv, 620-621. Gcigel, Eidiard: Die neuen Strahlen in der Therapie, Wiirzb. Abhandl., 1905, v, and vi, 189-216. Geiger, ff.: Neuere Forschungen liber die Alpha Strahlen, Pliysik. Ztschr., 1910, xi, 676-695. Gcllhorn, G.: Radiotherajw in Nonmalignant Gynecologic Diseases, Jour. Missouri Med. Assn., July, 192i, xviii, 220-224, — When to Operate and When to Use Radium on Fibroids of the Uterus, Jour.' Am. Med. Assn., 1922, cxxviii, 259-261. Geraghty, J. T.: Treatment of Bladder Tumors, New York Med. Jour., October 28, 1916, civ, 838-840. — The Results of Treatment of Bladder Tumors, Jour. Am. Med. Assn., October 20, 1917, Ixix, 1336-1342. — Value of Radium in the Treatment of Bladder Tumors, Southern Med. Jour., July, 1920, xiii, 511-514. GUlarducci, F.: Wirkung des Radiums auf Tuberkelbazillenkulturen, Strahlentherapie, 1914-1915, V, 284-291. . ^ -,. , i Gcisel F.: Ueber die Ablenkbarkcit der Becquerelstrahlen im magnetischcn Felde, Ann. der Physik. u. Chem., 1899. Ixix, 834-836. — Ueber radioaktive Substanzen und deren Strahlen, 1902, F. Enke Stuttgart. Ueber den Emanationskorper ans Pechblende und liber Radium, Bcr. d. deutsch. ehem. Gesellsch., 1903, xxxvi, 342-347. .Giifin., Herbert, Z.: Observations on the Treatment of Myelocytic Leukemia by Radium, Boston Med. and Surg. Jour., 1917, clxxvii, 686-691. — Splenectomy Following Radium Treatment for Myelocytic Leukemia, Med. Rec, New York, 191 S, xciv, 1020-1023. Gilchrist, T. Casper: Cancer of the Skin, Maryland Med. Jour., 191.), Ivni, I0/-I6I. Gircmd: Untersuchung liber die Absorption der Strahlen des Radiums dnreli einige organische Substanzen, Strahlentherapie, 1913, iii, 82-85. Glaesmer, Ernn: Das Strahlenkarzinom, Strahlentlierapie, 1914-1915, v, 275-283. _ Glaessgen, I.: Quellemanatorieu und natiirliche Radiumsolbiider, Radium in Biol. u. Heilk., 1911, i, 65-68. Glocker, B.: Ueber Absorption und Streuung der Rontgenstrahlen, Fortschr. a. d. Geb. d. Rontgenstrahlen, 1918, xxv, No. 5, pp. 421-436. GocTcel, A.: Radioaktive Emanation im Quellgas von Tarasp (Engadin), Chem.-Ztg., 190.5, xxix, 308. — Neueres liber Radioaktivitjit von Luft und Boden, Med. Klin., 1910, No. 44, pp. 1748-1750. 344 RADIUM THERAPY GoJdherg, S. W., and London. E. S.: Zur Frage tier Beziehungen zwischcn Becquercl- strahlen unci Haiitaffektioiicn, Dermat. Ztsclir.. lOO?.. x, 457-462. Gorges: Zur Mesothoriiiiiil)cliaiidlinig bei giclitischen unci nicht akuten rlieuniatisclien Leiden, Berl. klin. Wclinst-lir., 1913, No. 29, pp. 1345-1347. Corner: Ueber die Anwendung von Radium l)ei rheumatisc-hen Erkrankungcn, Miinchen. med. Wchnsehr., 1910, No. 27, pp. 1448-1451. Goitie, Leopold: Die Wirkung und Anwendung der Joachimsthaler radioaktiven Gruben- wasser, Zcntralld. f. d. ges. Tlierapie. 1907, xxv, 169-173. — Die Joaehimsthnler radioalvtiven Wasser in der Tlierapie, Wien. med. Wchnsehr., 1910, No. IS, pp. 1039-1044. — Eadiumbad St. Joac-himsthal, Wien. und Leipzig, 1911, Braumiiller. Gnibley : Ueber den weehselnden Gehalt der Atmosphare an Radiuniemanation, Eiu Beitrag zur Erklarung klimatisoher Einlliisse auf biologisehe Vorgange, Ztschr. f. klin. med., 1910, Ixxi, 338-343. Gracts, L.: Ueber neue pliysikalisehe Strahbingsforschungen, (Becquerelstrahlen und n. Strahlen), Miinchen. med. Wchhsclir., 1904, li, No. 14, pp. 598-602. Graff, E., von : Ueber die bisherigen Erfalirungen mit Eadium und Rontgenstrahlen bei der Krebsbehandlung, s'trahlentherapie, 1914-1915, v, 627-643. Graham, George H.: Radium and Its Medical Uses, Arch. Roentg. Ray, 1907, xii, 31-39. GrasnicTc, TV.: Die Wirkung der Radiumstrahlen auf thierisches Gewebe, Arch. f. mikr. Anat., xc. Part I, pp. 1-38. Graves, IVm. P.: Radium Treatment of Nonmalignant Uterine Bleeding, Some Im- mediate After-effects, New York Med. Jour., June 5, 1920, cxi, 969-972. Gray, J. A.: Secondary Gamma Rays Produced by Beta Rays, Proc. Roy Soc., 1911, Ixxxv, Series A, pp. 131-139. — and Wilson, W.: The Heterogeneity of the Beta Rays from a Thick Layer of Radium E, Philosophical Mag.," 1910. xx, 870-875.' Gray, E. TV., and Ramsy, Sir WiUiam: The Half -life Period of Radium; a Correction, Jour. Chem. Soc, 1910, xcvii, 185-186. — and — The Density of Niton (Radium Emanation) and the Disintegration Theory, Proe. Roy Soc, 1911, Ixxxiv, Series A, 536-550. Greef : Ueber Radiumstrahlen .unci ibre Wirkung auf das gesunde und blinde Auge, Deutsch. med. Wchnsehr., 1904, xxx, 452-454. Green, Alan B.: A Note on the Action of Radium on ^licroorganisms, Proc. Roy. Soc, London, 1904, Ixxiii, 375-381. Green, Stanley: Notes on Two Cases of Rodent Ulcer Treated by Radium, Lancet, London, March 19, 1904, p. 794. Grecnough, Tiohcrt B.: Radium in the Treatment of Carcinoma of the Buccal Cavity, ^ Boston Med. and Surg. Jour., 1918, clxxviii, 598-602. — The Value of Radium in the Treatment of Disease, Rhode Island Med. Jour., May, 1921, iv. No. 5,. pp. 71-76. — The Treatment of Tumors by X-rays and Radium, Boston Med. and Surg. Jour., June 16, 1921, elxxxiv. No. 24, pp. 622-627. Greinacher, 77.; Radium, Leipzig, 1907, Veit & Co. — Die Messung der Radium und Rocntgenstrahlen, Naturw. Wchnsehr., 1910, xxv, 657-668. — Die radioaktiven Elemonte und ilire Konstanten, Ztschr. f. Pliys. u. dititet. Thcrap., 1910, xiv, 138-141. — Uebor einen direkt zeigenden Tonenmessajiparat (Tonometer), Radium in Biol, unci Heilk., 1913, ii, 137-143. Grin, L.: Rar Radioaktivitjit, Berlin, 1911, A. Franke. Gndcrnalseh. J. F., and Bagg, JT. J.: Disturbances in the Development of IMammalian Eml)ryos Caused by Radium Kinaiiation, Reprinted from the Proc. Soc. Exper. Biol, and Med., 1920, xvii, 183-187. Gudzcnt, Frit.?: Ueber Dosierung und Methndik d-r Anwendung radioaktiver Stoffe bei inneren Krankheiten und die erzielten tiierapeutischen Ileileffcktc, Radium in Biol. u. Heilk., ii, 213-249, 272-283, 305-308, 313-329. — Der Einfluss von Radium auf die Iiarnsauren Salze De\itscli. med. Wchnsehr., 1909, No. 21, p. 921. — Kritische Bemerkungen zur der Arbeit: Vorstudien iilter Gicht von Bechold und Zeigler, Biodicm. Ztschr., 1909, xxiii, 275-277. l'.IIU,IO(!RAI'IIY 345 — PIi_vsik;ili.scli('liciiiis(li.'s \(i Iwiltcii dcr Ilariisiiuri' iiiiil iliror Siilzc ini l^liit, Med. Klin.. li)0!), No. Wl, y\k i:!81-l:{8.". — Uebor don gcsenwartioon Stand dor Radium enianations-tlicrapie, Thcrap. d. Gegcnw., DoccMnhor, IDIO, pji. 'yl'd -'>?,! . — Eadiuni und Stoffwoilisol, Med. Klin., 1910, Xo. H'. jip. 1>en iibor die Behandhnij^r dor Artliiitiden und der Giclit niit Radiunienianation, Beii. klin. Wclinselir., 1911, Xo. 47, pp. 209S-2101. — P^inijics iiber die bidlojjisclien Kiffenscliaften ilcr Radiunienianatidn und iliic An- wendung^ bei Kianklioiten, Radium in Biol. u. Ileilk., 1911, i, 14.34. — Ueber den Gehalt von Radiunieinanation ini Blute dcs Lebenden bei vcrseliiedcnen Anwendungsfoinien zu tlierapeutischen zweckcn, Radium in Biol. u. Ilcilk., 1911, i. 79-89. — Biolnuisoli-tlioraiieutische Versuelie mit Thorium und seinen Zerfallsprodukten, Ver- handl. d. Kono;. f. inn. ^led., 1912, xxix, 247-2.')7. — Zur Frape der A'ergiftuntj mit Tliorium-X, Berl. klin. Wchnsclir., 1912, No. 20, pp. 933-934. — Ueber Dosierunj^ und Methodik der Anwenduujj radioaktiver StofTc bei inncrcn Krankheiten und die erzielten Heilwirkungen, Berl. klin. Wehnstdir., 1913, No. 3.J, pp. 1597-1G02. — Einwirkung von Strahlen und radioaktiven Substanzen auf das Blut, Strahlcn- therapie. 1913, ii, 461-479. — Experinientelle Untersuchungen iiber die lieeinfiiissunj; von Ferment en dureli radioaktivc Substanzen, Straldentlierai)ie, 1914, iv, (i6(i-(i73. — Tlierapeutische PJrfalirungen Ijei Anwendung von Tlioriuni-X und Thoriumemana- tion, Cliaritc-Anu., 1913, xxxvii, 7-14. — Grundriss zum Studium der Radiumtherapie, Berlin and Wien., Url)an and Stdnvar- zcnberg, 1919. — and Halbcrstaedter, L.: Ueber berufliche Seliiidigungen dureh radioaktive Sub- ■ stanzen, Deutsch. med. Welmsehr., 1914, No. 13, pp. 633-635. — and Tlcrschfinkd: Versuelie ueber die angebliche Organaffinitiit von Tliorium-X, Strahlentherapie, 1916, vii, 519-526. — and Levy. M.: Vergleieliendc liistologiselie Untersueluingen iiber die "Wirkungcn von Alpha Beta Gamma Strahlen, Strahlentherapie, 1917-191S, viii, 53-58. — and Locircnthal : Ueber den Eintluss der Radiumemanation auf den Puriiistoffwcchscl, Ztsehr. f. klin. Med., 1910, Ixxi, 304-321. — , Maase, C, and Zondel', II.: Untersucdiungen zum narnsaurcstoffwechsel beini Mensehen, Ztsclir. f. klin. Med., 1918, Ixxxvi, 35-63. — und Xeitmann, Walter: Ueber die Durehljissigkeit der mensehlichcn Ilaut fiir Radium-emanation, Radium in Biol. u. Ileilk., 1912-1913, ii, No. 5, pp. 144- 147. — and TVinl-Jcr: Ueber die Behandlung vcn Psoriasis mit Tiioiium-X, Deutseli. med. Wchnschr., 1913, Xo. 20, pp. 925-926. CrttiUeminot, H.: Action Biologique comparee des radiations du radium et des radia- tions de Riintgeu, Arch, d 'electric, med., 1910, xviii, 325. — The Biochomie Efficiencv of Various Radiations, Arch. Roentg. Ray, 1910, xv, 90-97. — Ueber die zur Deutung in der Radiotherapie erzielten Resultate notwendigen physikaliselien Grundlagen, Strahlentherajiie, 1915, vi, 3;'.0-:'.39. Guisez, J.: Ueber die radiumthera])eutische Behaiidlinig des Oesopliaguskarziiuuus, Strahlentherapie, 1914, iv, 44-51. — and Lahoure: Presentation d 'un cas d 'epithelioma a forme grave de I'oesophage demeurant gueni depuis 2 ans V, par les a|>plications locales de radium, Presse med.. May 28. 1913, p. 439. Culhind, G. LoveU: Discussion on Radiations in the Treatnu'ut of Diseases of the Blood, British Med. .lour., August 20, 1921, pp. 271 •27.!. Gun.sctt, A.: Die Frage der Radiumbehandlung der gyn;ikcilo;,'ischen Krclise in Frank- reich, Strahlentherapie, 1914, iv, .36-43. Guttman, John: Railium in Rhinosclerema, Xew \ ork Med. .lour., October 2, 1915, cii, 711. Gtiycnot: Radium and Radioactivitv, Abstract of an Address, Lancet, London. October 1910, pp. 1153-1155. 346 RADIUM THERAPY Giiyot, G. : Exporiniontelle Uiitersueliungen iilior die Wirkung ties Radiums auf das Huutgewebe, Areli. f. Derniat. u. Sypli., 1909, xcvii-xcviii, 211-260. Guzman, Zacarias: Radiumtlierapia Contribution a la tecenica en aplieaciones en recto, Semana med., February 3, 1921, xxviii, 137-139. H Jlahs: Problome der Therapie niit radioaktiven Substanzen, Doutsdi. Gesellseli. f. Cliir., 1914, xliii, Part II, pp. 228-242. Haccker, V., and Lchedinsl-y, N.: Ueber komliiniertc Aetlicr- und Radiumwirkung auf Embryonalzcllcn, Miinclien. nicd. Wclmselir., 1914, No. 1, pp. 7-8. Ilacndly, Paul: Die Wirkung dcr Mesotlioriuni und Eontgenstrahlen auf das Karzi- nom, den Uterus und die Ovarien, Strahlentlierapie, 1913, iii, 300-307. — Anatomische Befunde bei mit Mesotlioriuni und Rontgcnstralilen behandelten Carci- nomen, Arch. f. Gynak., 1913, c, 49-69. Ualui, Otio: A New Radio-active Element which Envolves Thorium Emanation, Proc. Roy. Soc, 1905, Ixxvi, Series A, pp. 115-117. • — Ein neues zAvischenprodukt im Thorium, Physik. Ztschr., 1907, viii, 277-281. — Der Zerfall der radioaktiven Elemente, Beiheftc z. Med. Klin., 1907, pp. 33-64. — Ein kurzlebiges Zwisehenprodukt zwisehen mesothor. und Radioathr., Physik. Ztschr., 1908, ix, 246-248. — Ueber eine neuc Erscheinung bei dcr aktivierung mit Aktivium, Physik. Ztschr., 1909, X, 81-88. — Ueber Gesetzmafsigkeiten bei des Emission von B Strahlen und liber die Absorp- tion derselljen in Materic. Berichte d. Deutsch-jilivsik, Gesellsch., 1910, viii, 468-474. -- Ueber Mesothorium und Radiothorium, Physik. Ztschr., 1911, xii, 148. Hulhan, J.i Protektive AVirkung der Radiumemanation auf die sekundaren Sexual- charaktere der Tritonen, Zentralbl. f. Gyniik., 1914, No. 13, pp. 466-470. Halhcrstiidter, L.: Experimentelle Untersuchungcn an Trypanosomen iiber die biolo- gische Strahlenwirkung, Et-rl. klin. Wchnschr., 1914, No. 6, pp. 252-253. — Mesothorium Treatment of Hyperkeratoses of the Hands Due to the Roentgen Ray, Arch. f. Dermat. u. Syph., 1921, cxxx, 241. — and Goldstuclvcr, F. : Untersuchungen iiber die Biologischen Wirkungen der Ront- genstrahlen im Trypanosomenexperiment, Stralilentheiaj)ie, 1917-1918, viii, 35-52. Ualkin, Henri: Ueber den Einfluss dcr Beequerelstrahlcn auf die Haut, Arch. f. Dermat. u. Syph., Ixv, 201-220. HaUitiii, M. d' : Radium Treatment, Paris Med., June 11, 1921, xi. No. 24, p. 475. HaUopvau and Gadand: Sur Ics resultats du Traitement par le radium d'un lupus verruqueux, Ann. do dermat. et. syph., Paris, 1902, pp. 720-727. Hamm, A.: Radiotherapeutische Erfolge und Miszerfolge beim Uteruskarzinom, Strahlentlierapie, 1917-1918, viii, 161-165. Hammer, Frits: Die Radioaktivitat der Stebener Stahlquellen, Miinclien. med. Wchnschr., 1907, No. 8, .]). 373. Hammond, J. A. B.: The Use of Radium in a Case of Rodent Ulcer, Brit. Med. Jour., April, 1904, p. 946. Hampsun, TV.: Radium I^xplaiiied, London, 1005, T. C. and 10. C. Jack. Han ford, C. W.: Large and Small Doses of Kndium, Surg. Gynec, and Obst., Febru- ary, 1920, XXX, 210-211. — Radium Technic in Treating Cancer of the Eso]ihagus, Jour. Am. Med. Assn., January 7, 1922, ])p. 10-13. Hunscmaihn, 1).: Ueber Veriinderungeii der Gewebe und der Gesclnviilste nach Slralileii- liehandlung, Bcrl. klin. Wchnschr., 1914, No. 23, pp. 1064-1065. Hardin, Willct L.: Radioactivity, Radium, May, 1917, ix, 30-39. Hardy, W. B.: The Action of Salts of Radium upon Globulins, Proc. Physiol. Soc, May 16, 1903, pp. xxix-xxx. — and Anderson, H. K.: On the Sensation of Light Produced liy Radium Ray and Its Relation to the Visual Purple, Proc. Roy. Soc, 1903, "ixxii, 393-398." Haret : Die IVhandlung der Prostatahypertroiiliic (lunji die Radiotherapie, Strahlen- tlierapie, 1913, iii, 537-5-11. Harris, T. J.: Radium in Cancer of Larynx with Particular Reference to Dosage and Dangers in Its Employment, Laryngoseojie, November, 1921, p. 872. Harrison,- Frederick C.: The Use of Radium in Post-operative Conditions, Intcrnat. Jour, Surg., April, 1917, xxx. No. 4, pp. 97-103. i!ii;i,iO(!KAi'iiv 347 llai-tifjun, T. J. P.: 'V\w Tii'iitiiicut oi" " I'ort Wiiic" Xiicviis l>v Hjuliimi I'roiniilc, Brit. Jour, norniat., 1904, xvi, 4o2-4.'J4. — A Case of Coiificnital Pigmontod Xaovns, Brit. .Idiir. DtTinat., li'O.I, xvii, 14S. Harvey, T. W.: Radium Burn of the Yafrina Rosultiu^r in an Ilco-vaginal Fistula, New Jersey ^Med. See. Jour., Decenil)er 20, Ift^O, xvii, No. 12, p. 41.S. ITdstings, ,S.: On the Action of X-rays and Radium on the Bevolnpment of tlie Larvae and Moths of Silk Worms, Areh. Middlesex Hospital, London, 1910, xix, 2;]7- 243. — , MacCormac, II., ami If'oodnuui. E. M.: The liilliience of Pitchldende on Secondary Cancerous Skin X'odules, Arch. .Middlesex Hospital, 9th Cancer Report, 1910, pp. 127-136. llauRchting, TV.: Teehnie for Radium Treatment, Arch. f. Gyniik., 1920, cxiii, 1. Ab- stracted in Jour. Am. Med. Assn., December, 1920, Ixxv, lOSl. nauscr, Artur: Die Radioaktivitiit der Teidit/.-Schonauer Urquelle, W'ien. klin. Wchnschr., 1907, No. 2, ]ip. 45-49. Ifammann, Walthcr: Ucber Hamolvse durdi Radiiimstrahlen, Wieii. klin. Wchnschr., 1916, No. 41, pp. 12S9-1290. Kehert, A., and Kliiifj, A.: De Tintluence des radiations du radium sur les fonctions chlorophvUiene et respiratoirc cdiez Ics vegctaux, Compt. rend. Acad. d. sc, 1909, cxiix, 230-232. Ecclel, Edward B.: Report of a Case of Melanosarcoma of the Orbit, Treated with Radium, Arch. Ophth., 1916, xlv, 465-468. Ucidcnhain, L.: Die Aussichten der Strahlentherapic wider die Karzinome, Strahlen- therapie, 1914-1915, v, 25-50. Tlcidingsfcld, M. L.: Parakeratosis Variegata; Radium Treatment of Rhino].hyma and Hypertrichosis, The Lancet-Clinic, 1916, cxvi, 305-307. Ileimann, Fritz: Der Effekt verschieden gefilterter Mesothorstrahlung anf das Kan- inchenovarium, Strahlenthcrapie, 1914-1915, v, 117-121. — Zur Strahlcnbehandluno- der Uteruskarzinome, Berl. klin. Wchnschr., 1914, No. 1, pp. 12-14. Heimarl-, J. J.: Radium and the General PractitioiuM-. Jour. Lancet, ^^ay 15, 1921, xli, 2S4-287. Rcinccle, H.: Ueber die Einwirkung der Rontgenstrahlen auf Tiere, Miinchen. nu'd. Wchnschr., 1903, 1, 2090-2092. — Zur Kenntnis der Wirkung der Radiumstrahlen auf tierische Gewebe, ^Miinchen. med. Wchnschr., 1904, li, No. 31, pp. 1382-1384. — Wie verhalten sich die blutbildenden Organe bei der moderneu Ticfenbestrahlung? Miinchen. med. Wdmschr., 1913, Ix, 2657-2659. Zur Theorie der Strahlenwirkung, insbesondere iiV)er die Latcnzziet, Miinchen. med. Wchnschr., 1914. Ixi, No. 15, 807-810. — Allgemeines Exanthem nach lokaler Radiumbestrahlung, Strahlentlierapie, 1914- 1915, V, 216-218. Henri, Tietor, and Mai/cr, Andre: Action des radiations du radium sur les colloides, Compt. rend. Soc. de bit. reiul. Soc. do biol., 1904, hi, 2:!0-232. — Preciidtation des colloides positifs par les radiations ]> du radium, Cemi.t. rend. Soc. dc biol., 1904. Ivii, 33-34. Action des radiations du radium sur les colloides, riiemoglobin, les ferments ct les globules rouge, Compt. rend. Acad. d. sc, 19(t4, cxxxviii, 521-526. 11 enrich, Ferd : Untersuchuugen iiber die Thermahiuellen von Wiesbaden und deren Radioaktivitiit, Physik. Ztschr., 1907, viii. 112-114. — Ueber die Radioaktivitiit der gaze .ler Wiesbadener Thermahpiellen, Chem.-Ztg., 1909, xxxiii, 606. and Glaser, F.: Ueber die gebriluchlichen Ai>i)arate zur Bostimmung der Radio- aktivitiit von quellen, Ztschr. f. ang. Chemie, 1912. xxv, 16-19. HerscUfinkel, IT.: Die gamma Strahlenmessung von Ha-liuni und Mesothornnn, Strahlen- therapie, 1914, iv, 734-739. ,. , • , Uertwig, Gunther: Radiumbestrahlung unbefruchteter Froscheu-r und dire hntwu-k- lung nach Befruchtung niit normalem Sanien, Arch. f. mikr. Anat., 1911, Ixxvii, Part II, pp. 165-209. 348 RADITM THKRAPY — Das Scliifksal des niit RaoriniPiitellos und TluMniicut isdios iiluT ilif WirkiiiiK von an unlosliclic Riibstniizcn iilisorbierteiii Tlim iiiin-X nut" Tiinwiivn, Tlu'rap. d. Gofjcnw., lUKi, Ivii, 414-419. Uirz, Frans: Uohor Injc'ktinnon niit natiirliilicni ladioaktivoni Tlioinialwasscr dir.kt an dor quollo, Mihudion, nied. Wchnsclir., 1911, No. 2, ]ip. SH-ST. His, W.: Studien Ubcr Radiunionianation, ^lod. Klin., 1910, vi, No. 1(>. i)p. nili-fil.'i. — Die BohandUnijj dor Oiclit und des Rliouniatisnnis niit Radinni, Borl. kiln. Wi-lmsdir., 1911, Xo. 5, pp. 197-200. — Die clironisi-hon Aitliiitidon : Uvsaehon Eintcilunir mid T.iMirtciliin^'. Miindicn. nicd. Wclni.sclir., Iftll, No. ol, pp. 2408-2410. Unfl'mdn: Uohor dio Wirkini": dor Radiunistvaldon aiif P.aktoricn. l^vu^ Rundscliaii. 190.1, xiii, 91.3-917. — and Schitltz: Zur Wirkunoswoiso dor R()nt>;oiiliostrahlon Lo<'itliins aiif den tlii.T- isehen Organisnius, Wion. klin. Wclinsehr., 190.j, No. .1. pp. 114-11.". noffman., Frederick L.: Tlio Mortalit.v from Oaneor Tlirongliout the AVorld. Tlir Prudential Press, 191."j, Eadium and Kadiotliorapy, ])p. 209-212. n off ma II n, Erich: Uebor dio Podoutuuij dor StraldonbcliMudlnnij in dor Dornialobi;,']!' nebst BoMioi-kun<>on iibor iliro bi(ilo<>is(lio "Wiikimu, Stialdontliorapii', ICKi, vii, 1-32. Tlofmeier, M.: Zur frajjo dor aussclilioszliclion Straldonboliaudlunjr oporiorbaror Utor- uskarzinoino, Zontralbl. f. Gyuiik., 191.J. No. 1, ]ip. 1-4. Bolding, Arthur F.: The Rolativo Value of Radium in Donuatidoay. Jour. Am. Mod. Assn., Aufjust 29, 1914, Ixiii, 741-74.3. ■ — Tlie Treatment of Cancer liy Eleetrieal Methods witli and without Surgor.v and Radium. N(>\v York Med. Jour., September 19, 1914, pp. .j57-.")r)0. — and Long, IVilliam Bayard: The Truth Al)out Radioaotivo Therapy in Maliffiuint Growths, .lour. Am. Med. Assn., Septemltor 22, 1917, Ixix, 9S2-9S4. lloJIhnscn, Ilcrnmnn,: Uebor die Aufnahme dor Radiumomanation in das P.lut, Strahlon- thera])io, 191.3, ii, 50.3-514. Jfolzl-nccht, Giiido: Strahlentherapie, .Tahresk. f. iii/.tl. Fortbild.. Au-iist, 1914, v. No. 8, pp. 73-83. — and Exner, A.: Die Pathologie dor Hadiunuli'rmatilis, Kais. Akad. d. Wissons.-h., Wien, 1903, cxii. Part III, pp. 15.1-1 G2. — and Schwarz: Ueber Radiumstrahlen mit bosondorer Poriieksiohtijjunjr dor vorliiu- figen Mittoilunu- von E. S. London, Wien. klin. Wtdiusohr., 1903, No. 25, p. 749. — and— Ueber Radiumstrahlen, :Miin(-hen. mod. Wohnsohr., 1903, 1, No. 27, i». 11S9. IJolzner, Josef: YAw kasuistischer Boitrao- zur Radiuujhehandiung malignor Tumoren, ' Prag. mod. Wohnschr., 1913, No. 31, pp. 43()-43S. Horand, J?.; Permoabilite nu)indre de la peau do negre aux rayons X ot aux radia- ' tions des sols de radium, Lyon med., 1909, oxii, 21-22. Hiirdcr, Alexander: Kritischos Reforat iibor don Stand dor Thorium X Therapie und II P.orioht iibor Thorium X Trinkkuron in dor Praxis, Ztschr. f. Riintgenk. u. Kadiumforsoh., 1913, xv. No. 8, pp. 237-247; No. 9. I'p. 2S1.293. Jhirowilz: Cited in Das Radium, by E. S. London, Leipzig, 1911. Jldisley Sir Victor, and Finzi, K. S.: The Aotion of Filtered Ra.lium Rays wlion 'Applied Directly to the Brain, Brit. Med. .lour., October, 1911, pp. 898-900. Ilororla, Oscar von and Kroiifeld, A.: Vorgloichondo Volksmodi/.in, 190S-1909. Stutt- gart, Strecker and Schroder. Jtuhhard, J. E.: Indications for Use of Radium. Virginia Mod. Jour., .luue. 1921, xv, 404. Jlnael: Ueber natiirliche Radiumbiidor und (luollfassungon mit Ru.ksicht aut don Radiumgohalt dor cpiollon, Miindicn. mod. Wchnschr.. I'.tld. No. 21. p. i;i"9. imindinann: Vv\k'Y Loudon's uour \orsucIir mil Kadium, P..t1. mrd. Gosolls(di., 190 1, XXXV, 19.!. Inqraham, C. B.: Improssicuis Gained from the Use of IJadunn During the 1 :ist \ oar, Colorado Medicine, April, 1921, xviii, 72-7(i. Iredell, C. E., and Minett, E. P.: Notes on the Effect of Radium in Relation to Some Pathogenic and Nonpathogenic Bacteriii, Lancet, Lmidmi, May, 1909, pp. 1445-1447. .,.,,,■ T Isitani, P., and Mamihr. K.: I'.'Iht Uadinmoiuanat kmi emor (ioisriiioil.iii.'llo lu .lapan, /('■utralM. f. Klintuonslralilci,, 1911. li. sl-8S. 350 RADIUM THERAPY Jaioin, ^.; Pharmaco-biologie dii radium, Jour. med. de Brirx, 1910, xv, 499, 721. Jacohy, E.: Zur Radiumbehandlung des Trachoms, Deutsch. med. Wclinsclir., 1906, xxxii, 61-64. Jagan, P.: IJeber den Einfluss des Eadiunis auf die agglutinierende Fahigkeit des Blutserums von Typhuskranken (Russky Vraeh, 1903, No. 49) Ref. Miinehen. med. Wclmschr., 1904, Xo. 8, p, 359. Jagee, Nicolas, van Schwars, Gottioald, and Slebenroclc, Leo von: Blutbefunde bei Routgenologen, Berl. kliu. Wchnselir., 1911, No. 27, pp. 1220-1222. Jalcsch, E. von: Ueber Radium, Radiumemanation uud Radiumtlierapie, Prag. med. Wclmschr., 1910, No. 33, pp. 407-410. Jansen, H.: Untersuehungen iiber die bakterizide "Wirkung der Radiumemanation, Ztsehr. f. Hyg. u. Infeetionskrankh., 1910, Ixviii, 135-150. — Beliandlung med. Radiumemanation saerlig ved Gigtiske Lidelser, Ugesk. f. Laeger, 1910, Ixxii, 1333-1348. — Radium und Rheumatismus, Ugesk. f. Laeger, 1910, Cit. ZentralV)!. f. Rontgenstr. u. Radiumeman., 1911, No. 8, pp. 297-298. — a)}d Strandberg, 0.: Uudorsogelser over, om Radiumemanationens Bakterieiditet skyldes Ozonudvikling, Hospitalstidende, 1912, v, 61-66. Jancway, Henry U.: Radium Tlierapy in Cancer at the Memorial Hospital, N. Y., with the Discussion of Treatment of Cancer of the Bladder and Prostate. By Benjamin S. Barringer, and an Introduction by Gioacchino Failla, New York, 1917, Paul B. Hoeber. — The Treatment of Cancer of the Lip by Radium. A Report of Twenty Four Casoe, Jour. Am. Med. Assn., April 13, 1918,' Ixx, 1051-1058. — The Treatment of Uterine Cancer bv Radium, Surg., Gynec, and 01)st., September, 1919, xxLx, 242-265. Jccl:, Tloward S.: Apparent Cure of Carcinoma of the Bladder by Radium, Interuat. Jour. Surg., August, 1919, xxxii, 240-242. Jcntssch, Felix: Die Radioaktivitat der Kissinger Heilquellen, Physik, Ztsehr., 1907, viii, 887-890; 1908, ix, 120. Jessen, F. : Ueber die Behandlung von Nervosen im Hochgebirge mit besonderer Beriiek- sichtigung von Davos, Miinehen. med. Wchnschr., 1905, No. 35, 1675-1678. Jodlhauer, A.: Ueber die "Wirkung photodynamischer (fluorescierender) substanzen auf Paramacien und Enzpne bei Rontgen-und Radiumstrahlung, Deutsch. Arch. f. klin. Med., 1904, Ixxx, 488-491. — and Tappienir, H. von.: Wirkung der fluorescierenden Stoffe auf Spalt und Faden- pilze, Deutsch. Arch. f. klin. Med., 1905, Ixxxiv, 529-540. Joly, John: Radioactivity and Geology, An Account of the Influence of Radioactive Energy on Terrestrial History, London, 1909, A. Constable & Co. — On the Local Application of Radium in Therapeutics, Scicntfic Proc. Roy. Dublin Soc, 1914, xiv, 290-296. Jones, H. 0.: Radium in Gynecology, Jour. Am. Med. Assn., 1921, p. 1523; Surg., Gynec., and Obst., October, 1921, xxxiii, No. 4. Jones, Henry L.: On the Treatment of Naevus by Radium, Ba-it. iled. Jour., August, 1909, pp. 451-4^52. Jorissen, JV. P., and Binger, W. E.: Eintluss von Radiumstrahlen auf Chlorknallgas (und auf gewohnliches Knollgas), Bi-r. d. deutsch. chem. Gesellsch., 1906, xxxix, 2093-2098. Jiimon: Le Radium. Projuietes phvs. et therapeut.. Rev. de theiapeutique, 1903, Ixx, 692-695. Jung, Ph.: Zur Mesothoriuuibeliandlung von Genitalkarzinomen, Strahlentherapie, 1913, iii, 246-250. Jusim, L.: Erfahrungen mit Radium, Ztsehr. f. phvs. u. dititet. Tiierap., 1908-1909, xii, 505-506. K Kdliler, Otto: Zur Radiuialieliaudlung des Skleroms, Wicu. kliu. Wchnschr., 1905, No. 32, pp. 839-840. Kithlo, George I).: Tlic Use of Natural ami Artificially Prepared Radioactive Solutions in Internal Medicine, Pennsylvania ^Med. .lour., November, 1914, xviii, 126-129. Kiihn, Frit del: Thoriiim-X in der Therapie innerer Krankheiten, Strahlentherapie, 1914, iv, 376-381. Kai.'ffrling, ('.: Histologic der Radiumwiiknng. llandl). d. Radiuiiibidl. u. Tlierapie, by Lazarus, 1912, pp. 151-162. BIBTJOGRAPHY 351 Kalmann, A. J.: Eiu Beitrag zur Kenntiiis der Rniliunnviikung von Heilqiiellcn, "Wicn. klin. Wchnsclir., 1905, No. 22, pp. ;j(55-u()7. — Trinkversuehe mit dem radioaktivem Gasteincr Tlicniialwasst'i-, Ztsehr. f. jilivs. u. diiitet. Thcrap., 1907, xi, 20.1-213. Eaminer: Ueber die RadiinnbehaiHlhing d(M- Narlion, Borl. klin. "Wchnsclir., 1915, No. 18, pp. 465-466. Km\e, Evan O'Neill: Radium Tlicrapj-, Radium, April, 1916, vii, 16. Abstract of l)apcr read at Annual Mooting Elk County Mod. Soc, January l.^, 1916. Kaplan, Awadius: Uebor den Einfluss dos alkalisclion und radiumlialtigon alkalischon Wassers auf don Stickstoffwoclisol boim Gosundon und boim Giclitikor, Inaug- Diss., Berlin, 1912. Kardo-Sysoycff : Da.s Radium boi voi-sdiiodonon Tracliomformon. Russk. Vradi., St. Petersburg, 1906, x, 60.". KO'WJfman, H.: Das Radium und die Erschoinungi'n dor Radiciaktivitat, Stuttgart, 1910, Streekor and Schroder. Keatinff-Hart, dc: Association dos rayons X, du radium et des courants de haute frc quence dans le traitoment du cancer. Rev. de therap., 1906, l.wiii, 454. Keene, F. 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Gogenw., 1909, pp. 525-527. — Radiumiidialations-und Trinkmethode, Zentralld. f. inn. :Nred., 1912, xxxiii. No. 13, pp. 293-301. — and Mescrnitzl-y, P.: Ueber PurinslolVwochsol boi Gichtkrank(>n unter Radiuni- emanationsbehandlung, Thoraji. d. (iogenw., 1910, ])p. 526 528. Kenji-Kojo: Ueber die Biologische Wirkung des Mesothoriums, Borl. klin. Wehnschr., 1912, No. 17; 1)1). 779-781. Kennedy, Thomas C: Radium Treatment of Epitlulidma. .bnir. Indiana State ^fed. " Assn., July, 1916, ix, 298-300. Kennc, F. E.: Value of Radium in (iynocohigy. Now V<.rk Slate Jour, ^f.'d., .I.inuary, 1922, xxii, 1. Kerb, J., and La-arua, ]\: Zur Frage des Abbauos von Mommatriunuirat unfor dom Einfluss von RadiunuMuanation, hzw, Railiuin D., Biochom., Ztschr., Berlin, 1912, xlii, 82-90. Kenihaum, M.i Sur la decomposition do roan par li>s rayons B cr kiinstludic radiunu'inanatioiislialtijio Bsidor, liorl. klin. W.liiisilir., 1907, No. 23, pp. 719-721; ibid., No. 27, pp. S71-S72. — Beliandluiifj iiiit Liclitstralilt'ii und Radiiiinonianaliuii iin .laliic liiHlOl.", .Talire.^- kursc f. arztl. Fortlii'.dinig, 191."(, \\^ 7.">-80. Laqiteur, W., and Bcrf/witz: 1st die diirch Tiinken auf>jonoinmene Radiiinieinanation iin Urin iiaehweisbar? Ztsehr. f. exper. Path. ii. Tlierap., 1909, vi, 8()8-S7S. — and Lou-cnihii], S.: Uebcr die Aufiialiiiie von Radiiiniemanation bei Bade- iind Trinkkuien, Ref. :Miinc'hen. nied. Wchnsclir., 1907, No. 4."., p. 21()2. Lars, Edling : Erfaliriingon iiber Radiiinitlieiapie der Myonio und kliniakterischen Blut- uiigen des Uterus, Fortselir. a. d. Geb. d. R. 17sl. Laiipcr: Dilatations- und Radiumbehandlung des Speiseii)hrenkrel>ses, Verhaiidl. d. deutsch. Gesellsch. f. Chir., xxxvii, 133-13.'). Lavcran, Alphonse, and Mesnil, Frii.r: Try]i:in(isonu's et Tryjianusomiases, Paris, 1904, Masson and Cie. Lawson, A., and Davidson, D.: Radium in der Augenheilkumle, Miindien. med. Wchn.sehr., 1909, No. 4.'), p. 234S. Lazarus, Paid: Neunter Jahrcsbericht iilier die Anwenduno- der physikalischer Ileil- methoden in der I med. K'liiiik, Charite-Ann. Berichtsjahr., 190.j-190(;, xxxi, 41-58. — Radiumemanation, Verhandl. d. Kongr. f. inn. ^led., 1911, xxviii, 523.126. — Moderne Radiumtherapie, Berl. klin. Wchnschr., 1912, No. 14, ])p. 6:{3-().39. — Therapeutiselie Methodik der Radiumemanation, Deutsch. med. Wchnschr., 1912, xxxviii. No. 8, pp. 352-358. - — Blutanreichcrung mit Radiumemanation uml Messmethoilik, Berl. klin. Wchnschr., 1912, xlix, No. 25, pp. 1187-1189. — Radiumemanation und Jirunnengeist, Med. Klin., 1912, viii. No. 28, jjp. 1152-1156. — Experimentelle Grundlaoen der Radiumtherapie, Verhandl. d. Kongr. f. inn. Med., 1912, xxLx, 258-262. — Aktinium X-Behandlung, insbesondere der iHM-iiizidseii .\iiiimie, Berl. klin. Wt-hnschr., 1912, Ixix, No. 4S, ])p. 2264-22<)8. — Die Therapie mit Radioaktiven StotVen. Med. Klin., 191."., i\. No. 21, pp. 828-831. — Handliuch der Radiumbioloirie und therapie, X'eilag Herrmann, 191;!. — Zur Radiotherapie der Kar/.inome, l?<'rl. klin. Wchnschr., 1913, No. 28, pp. 1304- 1305. — Die Radium-^Iesothoriumanwendung bei inneren Erkrankuiifjen einschlieszlich der Neubildungen, Verhandl. (h'utsch. Kong. f. inn. Med., 1914, xxxi, 208-22i>. LazarKs-Barlotc, /I'. .S'. ; The Croonian I..i'ctures on liailio-activity and Carcinom.i ; ;in Experimental Iniiuir,v, I^ancet, London, June 26, 1909, pp. ]8(il-lSl7. — The Croonian Li-ctures on Radio-acti\ ity and Carcinoma: an Kx|iiriini'iit.il In quiry, LaJieet, London, June 26, 1909, ]ip. 18(11-1817. — On the Presence of Radium in Some Carcinom;itons Tiinuirs, I'roc. Ro,\'. Soc, London, 1912, Ixxxv, series b, ])]). 170-17.".. — Die Wirkung radioaktiver >Substanzen und deren Strahien auf normales und jiatho- logisches Gewebe, Strahlentherajiie, 191.3, iii, 365-37S. — Die Ursaehe und die lieiiung des Krelises ini Lichte der neiu'rcn r.idin bi(d(igis(dien Forschung, Strahlentherapie, 1915, vi, 173-192. 356 RADIITM THERAPY — An attempt at the Experimental Production of Carcinoma hy Means of Radium, Proe. Roy. Soe. Med., Section Pathology, 1918, xi, 1-17. — On Some Pathological Effects of Exposure to the Gamma-rays of Five Grams of Radiiun Bromide, Proc. Roy. Soe. Med., Section Pathology, 1920, xiv, 1-18. — and Bed-ion, H.: On Radium as a Stimulus of Cell Division, Arch. Middlesex Hos- pital, 12th Cancer Report, 1913, pp. 47-71. — and — • Note on the ''Time Factor" in Calculating Radium Dose, Arch. Middle- sex Hospital, 12th Cancer Report, 191.3, pp. 77-83. — and — Note on the So-called "Resting Stage" of Nuclear Division, Arch. Middle- sex Hospital, 12th Cancer Report', 191.3, pp. 8-1-86. — and Dunhar, T. J. D.: Experiments on the Action of Alpha, Beta and Gamma Radi- ations of Radium on the Muscle-Nerve Preparation of the Frog, Arch. Middle- sex Hospital, 12th Cancer Report, 1913, pp. 17-46. — - and — Comparative Observations on Changes in Columnar and in Squamous Epithelium, and in Sub-Epithelial Tissues Induced by the Gamma Rays of Radium, Arch. Middlesex Hospital, 13th Cancer Report, 1914, pp. 34-55. — and — On Retardation of Electroseopic Leak Following Estimation of Radium Emanation of the Order 10-7 Millicurie, Arch. Middlesex Hospital, 13th Cancer Report, 1914, pp. 91-109. — and — Experiments upon the Influence of Platinum Screens witli a View to Deter- mining Their Value in the Radium Treatment of Malignant Disease, Arch. Middlesex Hospital, 13th Cancer Report, 1914, pp. 131-140. Ledernmnn, P., and Kuznitslni, E.: Ueber die radiologische Behandlung von Nasen- rachengeschwiilsten, Strahlentherapie, 1917-1918, viii, 23-34. Lcc, G. H.: Us© of Radium in Gynecology, Texas State Jour. Med., April, 1921, xvi, No. 12, p. 530. Lee, John M.: The Modern Treatment of Cancer, Radium, July, 1915, v. No. 4, pp. 73-79. — Radium in Surgcrv and Gvneeologv, Jour. Am. Inst. Homeopathv, 1916, ix, 599- 616. Legnew and Clieron : Guerison par la radiumtheraine d'un cancer uretro-vaginal in- operable, Bnll. Soe. d. Chir., March, 1914, xl, 297-303. Lejars: Recidive inoperable de cancer du sein traitee avec succes par la radio- therapie, Presse med., 1904, No. 97, p. 774. Lenlcei, W. D.: Beitrage zur Methode der Bestimmung des Radium-emanations-gehaltes, Ztschr. f. diatet. u. physik. Therap., xiv. No. 4, pp. 193-204, 268-277. Lepper, E. : Experiments to Determine Whether Variations in Temperature Influence the Effects Produced when Malignant Cells are Irradiated by Radium Bromide, Arch. 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Mayehn, G.: Experimentelle X^ntersuchungen iilKM- die Pathogenese der Dickdarmsch- leimhauthanuirrhagien nach der intravencisen Tiiorium X-Injektion. Internat. Beit. z. Path. u. Therap. d. Ernahningsstor., iv, Xo. 4, pp. 471-483. Mayer, CarJ : Die Radiumtherapie in der Praxis, Radium in Biol. u. Heilk., 1912, i, 341- 349. Mayo, W. J.: The Relation of Surgery to the Prolongation of Human Life, Surg., Gynec, and Obst., January, 1920, xxx, 23-26. Meidner, S.: Die Behandlung ])osartiger Gesehwiilste mit radioaktiven Substanzen, Therap. d. Gegenw., 1912, liii. 63-67. — Bericht iiber einige mit jVEcsothorium behandelte Fiille von inoperablem :Mastdarm- und Speiserolirenkrebs, Therap. d. Gegenw., 1913, ]>p. 447-451. Der gegenwjirtigc Stand der Mesothoriumtherapie gyniikologischer Carcinome, Therap. d. Gegenw., 1913, .liv, 406-410. — Weitgehende Beeinilussung eines Portiocarcinoms durch mesothoriund.estrahlung, Therap, d. 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Assn., January 1, 1910, Ixvi, 1(1.' — Remissions in Leukemia Produced bv Radium in Cases Comidetely Resistant to X-ray and Benzol Treatment, Boston Med. and Sur-r. .Tour., 1917, clxxvi, 49nri0n. Oiidin. and Verdure: Du Radium en Gvnec(do;iie, Comjit. rend. Acad. d. sc, 190(i, cxliii, 90-92. Pagensteeher, Alexander: Ueber Banertlieraine, Straldentlierapie, v, 401-100. — Ueber die praktisclie identitat von Radium- und R(intj;enstralilun>,', Miindien. nird. Wehnsehr., 1913, Xo. 40, pp. 2r>{]2-2~A]X Pancoast, Tlenry K.: ■^^alia•nant Disease of the Throat and Sinuses, .tour. Am. Mrd. Assn., Sei)tember 22, 1917, Ixix, 980-9S2. — Nonsurgical irethods of Treatinor Cancer, Xew Vork Med. .Tour., May 1«, 1921, exiii, 740. -— Treatment of Brain Tunu)rs bv Radiation. Am. .lour. Roenti,'enolozi^i-, 1912. xiv, Part T, pp. 1-12. — and Plcscli, J.: Einifje eroebnisse iiber experimentelle und histolorjische Untersuch- ungen zur Erforschunji- der Wirkung des Thorium X auf den tierischen Or- ganismns, Berl. klin. Wchnschr., 1912, xlix, l.'U2. Pari; Franeis E.: The Treatment of Disease bv Injections of Deep Sea Water and Radium, Slod. Roe., Xew York, April 29, 1910, Ixxxix, 7S2-7S.3. P'artos, E.: Ueber die biologische Wirkun^ der kondensierten Radiumemanation, Berl. klin. Wchnschr., 191.5. Xo. S, pp. 181-18."?. Paschlis, R., and Tiitinfier, W.: Radiumbehandlunij eines Prostatasarkoms. Wieii. klin. Wchnschr., 1910, Xo. 48, pp. 171.')-! 710. Piissler: Ueber den Ersatz der sotjenannten indifferenten Therm.-ilbiider durch Inhala- tion ihrer Radiumema nation bei rlieumatisdien Krankheiten, Miindien. med. Wchnschr., 1910, Ivii, 1819-1S22. Pasteau, A., and Deqrais: De I'emploi du Radium dans le Traitement des Cancers de la Prostate, Jour, d'urol. med. et cliir., 191."?, iv, .■'.41-P.0(;. Payne, B. L.: Conservative Api-lication of Radium in Benign Conditions of the I terus. Viro-inia Med. Month., Fdnuavy, 1921, xlvii. Xo. 11, pp. ;')2.1-.127. Peahody Franeis W.: Uovort on the Treatment of ^lydogenous Leukemia with Radium, Boston ifed. and Surjr. Jour., 1917, dxxvii 8'.r8/4. ^ PeJiam, H.: Zur RadiumbdiandlmiK in der Gyniikolo-.e, Wien. klin. ^Ndmschr.. l.H.., xxvi, Xo. 41. pp. 10.-)(I-1(m1. PeUiszari, Cclso: Adenocarcinoma cilindrh,. .Id retto in euro c,d radium. Rito.m.. med., 191.1, xxxi, .",09-.^10. . , ^. . ,,- i, = Pemherlon., Frank A.: Hemorrhage from the Uterus iii the Nonpregnant A\..man, B<.s- ton Med. and Surer. Jour.. 1918, dxxviii, 4S;,-492 Percy, James F.: The Yalue of He:.t in the Treatment ot ^^^'^^'^'/'^^^^''^ J^]:"^ able Uterine Carcinoma. Pennsylvania Med. Jour., .Tanuary, 1910, x.x -?( - 4., Perrier C: Radium Treatm.-nt <.f Lympliosarconi:i in 1 ..nsil. Rev. Med. de la Suissi Romande, Geneva, October, 1921, xli. i-. 0,.). -, „ ,- , , , „, ^„f Perthes, G.: Yersud.e iiber den Einfluss der Rr.nt^nmstrahhM. und Radiinnstrahlen anf die Zellteilunff, Deutsdi. med. Wclinsd.r., 1904. xxx Xo. J ' • I'P- . •i'-''-^- — Umfrajre iiber die behn.ulluu- das Kvcbses m.t Radium, Med. Klin., 190... i, No. 13, p. 307. 364 RADIUM THERAPY — Ueber die Strahleiibeliaiidlung- bosartiger Gescliwulste, Arch. f. klin. Chir., July 30, 1921, No. 2, pp. 353-370. — a7id Jiingling, 0.: Plastic Radium Ai^plicator for Buccal Cavity, Jour. Am. Med. Assn., 1921, p. 979. Verugia, Alfreds: Carcinoma del palate duro guarito col radio, Gazz. d. osp., 1905, xxvi, 12-16. Fetcrson, E.: Therapeutische Versuche mit Eadium, Miinclien. med. Welinsclir., 1904, li, No. 21, p. 946. — Om Indikationerne fiir Radiumbeliandligcn auf Carcinoma uteri, Hospitalstidende, June 1, 1921, Ixiv, No. 22, pp. 342-348. Petit, G.: Radioactive Therapeutics, Presse med., March 12, 1921, xxix, 201. I'fahJer, G. E.: An Inexpensive Radium Capsule Holder, Am. Jour. Roentgenology, January, 1921, viii, No. 1, p. 30. — Radium Combined with Roentgen-Ray Treatment in Carcinoma of Breast, Am. Jour. Roentgenology', November, 1921, p. 661. — The Treatment of Carcinoma of the Thyroid by the Roentgen Rays and Radium, Am. Jour. Roentgenology, 1922, ix, 20-25. Pfciffcr, R., and Friedbcrgcr, E.: Ueber die bakterientodtende Wirkung der Kadium- strahlen, Berl. klin. Wchnschr., 1903, xl, 640-641. P fender, Charles A.: Roentgentherapy in Malignant Tumors of the Parotid Salivary Gland, Med. and Surg., June, 1917, i, No. 4, pp. 366-375. PJiillips, Wendell C: Experiments with Radium Emanations, Med. News, 1905, Ixxxvii, 341.343. Phisalix, C: Influence des radiations du radium sur la toxicite du venin de vipere., Compt. rend. Acad. d. sc, 1904, cxxxviii, 526. — Influence de 1 'emanation du radium sur la toxicite venins, Compt. rend. Acad. d. sc, 1905, cxl, 600. Pieper, Josef: Ueber den Gehalt des arteriellen und venosen Blutes an Radiumemana- tion bei Airekter Einfliihrung der Emanation in das Duodenum, Ztschr. f. Rontgenk. u. Radiumforsch., 1912, xiv, 352-367, 391-405. Pigache, B., and Beelere, H.: Kystes cilies du thymus, Bull. mem. de la Soc. Anat., 1911, xiii. Series 6, pp. 13-32. — Action des rayons de Roentgen sur les corpuscles de Hassall, Bull. mem. de la Soc. Anat., 1911, xiii, Series 6, pp. 47-54. Pinch, A. E. Hayward : A Report of the Work Carried out at the Radium Institute from August 14, 1911, to December 31, 1912, Brit. Med. Jour., January, 1913, pp. 149-163. — Arbeitsbcriclit aus dem Radiuminstitut in London, January 31, to December, 1913, Strahlentherapie, 1914-1915, v, 12-24. — A Report of the Work Carried out at the Radium Institute, London, in 1914, Brit. Med. Jour., February 27, 1915, pp. 367-372. — A Report of the Work Carried out at the Radium Institute, London, from January 1, 1917, to December 31, 1917, Radium, July, 1918, xi, No. 4, 49-72. — Tlie Treatment of Arthritis Deformans with Radium-emanation Solution, Report of the London Radium Institute, Radium, November, 1918, xii, 20-21. — A Report of the Work Carried out at the Radium Institute, London, from January 1, 1918, to Decemlwr 31, 1918, Radium, August, 1919, xiii, 49-59. — A Report of the Work Carried out at the Radium Institute, London, January 1, 1918 to December 31, 1918, Conclusion, Radium, September, 1919, xiii, 65-84. — A Report of Work Carried out at the Radium Institute, London, from January 1, 1919 to December 31, 1919, Part I, Radium, August, 1920, xv, 69-82. — A Report of the Work Carried out at the Radium Institute, London, from January 1, 1919, to December 31, 1919, Part 2, Radium, September, 1920, xv, 85-97. — Radium Therapy in Uterine (\Tncer, Brit. Med. Jour., June 18, 1921, No. 3155, pp. 881-884; Piiikus, A.: Zur Mcsotliorinintlieiajjic bci Krebskrauken, Berl. klin. Wchnschr., 1912, No. 20, pp. 935-937. — Ueber die Erfolgc der Mesotlioriniuljcstrahlung bei Karzinom, Berl. klin. Wchn- schr., 1913, No. 24, pp. 1105-1107. — Die liehaiidlung des Krebsos mit Mesotlioiium und iliro Koml)ination mit anderen Verfahren, Deutsch. med. Wchnschr., 1913, No. 36, pp. 1720-1722. — Weitere Erfahrungen iiber die Mesotlioriumbcstrahlungstherapie bei Karzinom, Berl. klin. Wclinsciir., I!tl4, No. 5, pp. 207-209. mRI.TOORAI'HY 365 — Weitere Erfahmnojcn u])cr die konsorvativc Behaiulhin}; flor UtcnisblntuTigen inid Myome mit Mesotlioriuni- Eaor]. klin. "Wclmsclir., Iitl2, Xo. 10, pp. 739-741. — Ucber cliemische Einwirku)ii>on dos Tlioriuni- X auf orjjanische Substanzon, be- sondcrs auf die Harnisauro, P>orl. klin. AVchnsclir., 191.3, No. 11, pp. 323-.'524. — Ueber die Verteihing und Ausschoiduno- radidaktivcr Substanzon, Berl. klin. Wohn- selir., 1914, No. 34, pp. 1;"3-1.374. — and Karczag, L.: Uobor 'r]i()ts von Radiuni- bleiver1)indnngon (Zorfallsprodukton dor Radiumemanation) Zioglor's Zon- tralbl. f. allg Path. u. Anat., 1913, xxiv, 246-247. Frescott, S. C: The Effect of Radium Rays on the Colon Bacillus, the Diphtheria ]?a- eillus, and Yeast, Science, Xew Ytn-k, 1904, xx, 24(i-24S. Pi-ice- J ones, C.: Radium, X-rays and tiio Living Cell, 1915, Ctdwoll and Kuss, p. 178. Prime, Frederick: Observations ujion the Effects of Radium on Tiss\io Growth " i;i Vitro", Jour. Cancer Research, April, 1917, ii, 107-1 30. — and Eohdcnburg, G. L.: P^ffect of Conibinod Radiation and lloat on X'ooplasins, Arch. Surg., January, 1921, ii, 116. Proeschcr, Fredericl: : The Intravenous Injection of Scdublo Radium Salts in Man. Radium, July, 1913, i, Xo. 4, pp. 9-10. — The Pathological Anatomical Changes in Guinea Pigs Killed by Expos\ire to High Concentration of Radium Kmanation, I, Radium, August, 1913, i, Xo. 5, jip. 5-8. — The Pathological An.-itomical Ciiaiigos' in Guinea Pigs Killed by Exposure to High Concentration of Kadium l']maiiati(iii, 11, Hailium, Sciitombcr, 1913, i, X^o. 6, pp. 9-14. The Intravenous Injections of Soliiblo R:o1ium Salts, Ra.lium, .lanuary, 1914, ii, Xo. 4, pp. 45-53. — The Intravenous Injection of Soluble Hailimu Salts !!, Radium, February, 1914, ii, Xo. 5, pp. 61-64. — The Intravenous Injectiiui of Sdlublc Wadium Salts III, Radium. Mar.h, 1914, ii, No. 6, pp. 77-87. 366 RADIT'M THERAPY The Influence of Intravenous Injection of Soluble Railium Salts on High Blood Pressure, Eadium, Ajiril, 1014, iii, Xo. 1, 1-10. The Influence of Intravenous Injections of Soluble Radium Salts on High Blood Pressure. II, Radium, May, 191-4, iii, No. 2, pp. 17-21. — Contribution on the Therapeutic Value of the Intravenous Injection of Soluble Radium Salts in the Treatment of Pernicious Anemia and Leukemia, Radium, June, 1916, vii, No. 3, pp. 71-77. — Conclusions Concerning the Value of Radium Therapy in Pernicious Anemia, Radium, July, 1916, vii. No. 4, pp. 102-109. — (Uid Almqnest, B. R.: Contribution on the Biological and Pathological Action of Soluble Radium Salts with Special Reference to Its Therapeutic Value in Pernicious Anaemia and Leukemia, Radium, August, 1914, iii, No. 5, pp. 65-71. — and — Contribution on the Biological and Pathological Action of Soluble Radium Salts, II, Radium, September, 1914, iii, No. 6, pp. 8o-9o. — «)i^Z — Contribution on the Therapeutic Value of the Intravenous Injection of Soluble Radium Salts in the Treatment of Pernicious Anaemia and Leukemia, Radium, January, 1916, vi, 8.J-96. Pusey, JVilliam Alien: Radium in Cutaneous Lesions, Pennsylvania Med. Jour., No- vember, 1914, xviii, 134-136. Q Quid-, Douglas: The Condiination of Radium and the X-ray in Certain Types of Car- cinoma of the Breast, Surg. Gynec. and Obst., February, 1921, xxxii, 156-168. -— The Conservative Treatment of Cervical Lymphatics in Intraoral Carcinoma, Jour. Am. Med. Assn., August 6, 1921, p. 436. — Radium Technique in Treatment of Malignant Diseases of the Skin, Arch. Der- mat. and Syph., September, 1921, iv, 322-341. — and Johnson, F. M.: A New Type of Applicator for Use with Radium Emanation, Am. Jour. Roentgenology, 1922, ix, 53-55. Quigley, D. T.: The Relation of Radium to Surgery, Med. Herald, 1915, xxxiv, 5-9. — - Preliminary Report of a large Angiomatous Tumor in Baby, Treated by Radium, West. Med. Rev., 1915, pp. 235-236. — Tlie Technic(ue of Radium Application, Minnesota Med., March, 1919, ii, 97-99. — Radiotherapy in Cancer, Nebraska Med. Jour., September, 1921, vi, 280. R Ramsmier, Carl: Ueber die Aufnahme der Radiumemanation in das Blut, Physikalischer Teil, Strahlentherapie, ii, 515-532. — Ueber Kreuznacher Aktivatorkonstruktionen, Miinchen. med. Wchnschr., 1910, No. 28, pp. 1499-1501. — and Cav Radium, Laneet-Clinic, 1014, cxii, 01 S. — and Ransohoff, Jnneph: Kailium Treatment of Uteriiu' Fibroids, Laneet-Clinic, IDlf), cxv, 11 '6-1 IS. — ayid — Radium Treatment of Uterine Cancers, .\nn. Surg., 191 fi, Ixiv, 29S-30.3. Rami, E., ScMUler. H., and Sparmanii, R.: Frfahrunfjen iiber Radiumbehandlung der maliftnen Tumoren, Wien. klin. Wchnschr., 191:5, xxvi. No. 41, pp. 16.31-lG(jl. Rdvc, F.: Die Rontoentherapie bei Strumen und morbus Basedowii, Ztschr. f. Rijnt- genk. u. Radiumforsehr., 1911, xiii, ?,7 and 9(5. Rdvoicl, L. J.: Resume of Action and use of Radium and Roentgen Rays in Thera- peutics, Jour. South Carolina ^led. Assn., April, 1921, xvii, (]9. Rinpnond and Zimmeni: Quelques faits' rclatifs a Taction therapeutique du radiiun. Bull, d. Acad. d. med., Paris, 1904, lii, ISDISI. Recasens, S.: La radiunitherai)ie dans Ic cancer ilc I'uterus, .Ardi. mens, d'olist. et de gynec, 1917, ix, M-5'). — Variations dans la technique des ai>plicatious du railium dans les differentes formes du cancer cervical de I'uterus, Ardi. mens, d'olist. et de gvnec., 1919, xi, 676-697. — The Technique of Applying Radium in the Various Types of Cancer of the Cer- vix of the Uterus, "internat. Abst. Surg., 1920, xxx, 468. Redpeld, A. C, and Bright, E. M.: Effects of Radium Rays on :\retabolism and Crowth in Seeds, Jour. General Physiology, 1922, iv, 2ii7. Rcgaud, C: Radiotherapy of Cancer of Tongue, Paris, nu'd., April 2, 1921, ii. No. 14, p. 26.5. — Dangers of Radium, P.ull. d. Acad. <1. nu'"d., Paris, :\rav 24, 1921, Ixxxv, No. 21. p. 608. — Radium Treatment of Uterine Cancer, ^Mediciiu', Paris, .lune, 1921, ii. No. 9, p. 725. — and Cremieu, R.: Fondements exjierimentaux de la Rontgentherapie appliquee a I'hypertrophie du thymus. Arch, d'electrie. med., 1912, xx, 4S1-499. — and — Action des rayons X sur le thymus du cliien. Arch, d'electrie. med., 1912, xxi, 144-14.5, 597-598. — and — Sur la suppre.ssion definitive du Tissu thymique par la Rontgentherapie, Compt. rend. Soc. de biol., 1912, Ixxii, 52;{-525. Regener, Erich: Uebcr Zahlung der a-Teilchen durch die Szint illation >ind die Griisse des Elektrischen Elementaniuautums, Per. deutsch. Pliysik. Gesellsch., 1908, vi, 78-83. — Beobachtung szintillierender Fluoresenz, hervorgerufea dun-h P. Strahlen, Ber. deutsch. Physik. Gesellsch., 1908, vi, .351-35.3. Rehns, Jides: Note sur quehiucs actions du Radium, Compt. rend. Soc. d. biol., 1!'04. Ivii, 206-207. — Sur Quelques eflfets du Radium, Comjit. rend. Soc. biid., 1905, Iviii. 491-492. — and Salmon, Paul: Inlluence ilu Radium sur Ic Psoriasis, Compt. reml. Soc. d. biol., 1905, Iviii, (IM-CKi. — and — Traitement du cam-er cutaue par Ic radium, Compt. rend. .\c;id. d. sc., 1905, cxl, 1723-1725. Rrichaii, Karl: Die Radioaktivifiit der scldesisclK ii I h'ilqucliiMi. Iriaug.-Diss., Halle. 1908, Ivaemnierer. Rcichcr, K., and Lenz, E.: Weitere ^Mitteilungen zur Verwendung der Adrenalinaniiniie als Hautschutz in der Rontgen- >iud Ra10, clix, S85-898. Retwn Louis-: Die Radiumtherpie de 1 leucemie^ myeloide, Semaine med., IPl.", No. 29, p. 348. — and Degrai-a: Radium Thera]>y of Myeloid Leukemi:i, Lull, et nu'm. Soc. me(l. d. hf)p. de Paris, December 10, 1920, xliv, No. :tS, )>. 1511. — and — R:idium Treatnu'nt (d" Leukemia, Hull, .\cail de med., Paris, February 15, 1921, Ixxxv, No. 7, p. 2117. 368 RADIUM THERAPY — ^ — ^ and Deshouis: Radiumtherapie de la leucemie myeloide, Bull, et mem. Soe. med. d. hop. de Paris, 1913, xxxvi, 54-66, 649-651. — ^ — , and Dreyfus, L.: Eadiumtherapie der myeloideu Leukamie, Strahlentherapie, 1913, iii,551-552. . — J — , and Thioaui : De la non-intervention de la rate dans Paction leucopenique du radium sur la leucemie myeloide, Compt. rend. Soc. d. biol., 1913, Lxxiv, 937- 940. — , — , and Toiirnemelle : Radium versus Rontgen Ray Treatment in Splenomyelogen- ous Leukemia, Ahstr. New York Med. Jour., July 17, 1915, cii, 148. — and ILarie : Essai critique sur la radiumtherapie des infections aigues i^ar les in- jections de sulfate de radium, Arch, d 'electric, med., 1910, xviii, 326. Bepin: Radioactivite de certaines sources goitrigenes, Compt. rend. Acad. d. sc, 1908, cxlvii, 387-388. — Nouvelles recherches sur la radioactivite des sources goitrigenes, Compt. rend. Acad. d. sc, 1908, cxlvii, 703-703. JRepman, A.: Treatment of Cancer witli Radium, Jour. Nevropat i. Psikhiat... Korsa- kova, Mosk., 1904, iv. Part 2, pp. 69-72. Rescheiillo, D. B.: Das Radium und seine Anwendung zur Behandlung von Hautkrank- heiten, bosartigen, Neubildungen und einigen inneren Krankheiten, St. Peters- burg, 1910, Russich. EetM, L.: Das Radium in der Laryngo- Rliinologie, Strahlentherapie, 1914, iv, 52-94. lieiisch: Mvxosarkom bei 16 jahrigem Madchen durch ]Mesothorium geheilt, Zentralbl. f."Gynak., 1916, No. 2, pi 37. TJieinholdt, M.: Zur baktericiden Wirkung radioaktiven Mineralwassers, Berl. klin. Wchnschr., 1906, No. 20, pp. 636-637. Rihardeau-Diimas and Weil, Albert: Zur un cas d 'hypertrophic du Thymus traitee par la radiotherapie, Gaz. d. hop., 1912, Ixxxv, 568-569. Bicliards, A.: Recent Studies on the Biological Effects of Radio-activity, Science, 1915, xlii, 287-300. BicJmrds, Theodore IF., and Lemheri, M. E.: The Atomic "Weight of Lead of Radio- active Origin, Jour. Am. Chem. Soc, 1914, xxxvi, 1329-1344. Bieliet, Charles: Influence de 1 'emanation du radium sur la fermentation lactique, Arch, internat. de physiol., 1905, iii, 130-151. Bicliter^ Paid, and Gerhartz, S. : TJeber die Einwirkung der Rontgenstrahlen auf Fermente, Berl. klin. Wchnschr., 1908, No. 13, pp. 646-648. Bicl-er, G.: Mesothorium und Gefasznerensystem naeh Beobachtungen am Kanlnche- nohr, Strahlentherapie, 1914-1915, v, 679-741. Bicdel: Untersuchungen iiber die kiinstliche Radiumemanation, Med. Klin., 1908, xii, 405-407. — Messungen von Radium-Emanation, Ztschr. f. exper. Path. u. Therap., 1909, vi, 882-889. Biehl, G.: Karzinom und Radium, Wien. klin. Wchnschr., 1913, xxvi. No. 41, pp. 1645- 1647. — Radium and Krebs, Strahlentherapie, 1914, iv, 19-26. — Radiumtherapie, Wien. klin. Wchnschr., April 21, 1921, xxxiv. No. 16, pp. 182-183. Bisley, E. E.: Radium in the Treatment of Carcinoma of the Cervix Uteri, Ann. Surg., December, 1920, Ixxii, No. 6, pp. 701-711. — and Lehind, George A.: Report of Treatment of Carcinoma of Cervix at the Hunt- ington Hospital for Period of Four Years, Boston Med. and Surg. Jour., • 1917, clxxvii, 891-894. Boharts: Practical Radium. The Practical Uses of Radium in the Treatment of Obstinate Forms of Disease, St. Louis, 1909, Nixon- Jones. Bobin, Albert, and Cawadias : Svringo-nivelie traitee par le ladium, Presse med., 1913, No. 24, p. 238. Boden, P. A., and Willinsohn., John.: Radioactivity a. Property of the Droitwich Brine Baths, Lancet, London, April, 1904, p. 1010. Bodenhaugh, F. H.: Modern Radiotherapy, California State Jour, iled., April, 1921, six, 156-159. Bohdenhurg, G. L., and Bnllocl:, F. D.: Tlic Influence of Heat and Radium upon In- ■ duced Immunity Against Transplanted Animal Tumors, Jour. Cancer Re- search, April, 1918, iii, 181-191. Bidand, M. M.: Roentgen Ray and Radium Treatment of Carcinoma of the Uterus, Oklahoma State IMed.* Assn. Jour., February, 1921, No. 2, p. 30. Bolleston, H.: Preliminary Report of X-ray and Radium Protection Committee, Arch. Radi(d and Electrotli.. .June, 1921, xxvi. No. 1, pp. 5-9. lUHMOCHAl'llV 369 Bosenbloom, Jacob: A Study of the Urinary Nitrogen and Sulphur Partition in a Case of Rheumatoid Arthritis Treated with Intravenoup, Tniections of Radium Salts, Am. Jour. INIed. 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Wehnschr., 1916, No. 10, pp. 341-344. — Vcrbreituug von Mesothoriuni Energie im Ivorper der therapeutisch Bestrahlten, nachgewiesen durch Photoaktivitat, Miinchen. nied. Wehnschr., 1916, No. 16, pp. 560-562. Schivyzer, Arnold: Radium: Its Therapeutic Uses in Surgery, Minnesota Med., Sep- tember, 1921, iv, 533-538. Scott, S. G.: Dual Radiotherapy in ^Vfalignant Disease, Brit. Med. .Jour., London, May, 28, 1921, No. 3152, pp. 771-773. Secl:f, Han.'i: Die Wirkung der Rontgen- und Radiunistrahlen auf die Pflanze, Natur. Wehnschr., 1900, xxi, No. 24, ]ip. 369-372. Scil, Harvey A., Viol, Charles JI., and Gordon, M. E.: Tlie Elimination of Soluble Ra- dium Salts Taken Intravenously and per Os, New York Med. Jour., May 1, 1915, ci, 896-898. Seldin-, Meiktch: Uel)er die Wirkung der Roentgen- und Radiunistrahlen auf innere organe und den Gesamtorganismus der Tiere, Diss. Konigsburg, 1904, i, O. Kiimmel. Selenlovsly, J. W.: Zur Frage iiber die Ileilung des Trachoms durch Becquerelstrahlen, Arch. f. Angenh., Wiesb., 1908, Ix, 6:!-92. Selig, A.: Die Behandlung inoperabler Geschwtilste mit Radium, Med. Klin., 1908, iv, No. 30, pp. 1149-1151. Sella, A.: Ricerche di radioaltivita indotta, Reale Acadeniia dei Lincei Rendieonti, 1902, Series 2, pp. 81-89. Sereni, S.: Azione de radium sul pus vaccinico, II Policlinieo, 1908, Ref. Berl. klin. Wehnschr., 1908, No. 23, p. 1105. p.im.iocKAi'HY 373 Seuffcrt, Ernjit von: Die Krfiilirmi;;iMi iIit Kiliiijil. ITiiivcrsitiits-Frauciikliiiik Miiiicluii (Dootlerlcin) iiiit 1)l(Miic luul Greiizon tltT StralilciilKliaiKlliin^ dos Krcliscs, 8tralik-ntlioift])it', 1J»1 K iv, 74n-7>l4. — .Straliloiitii'tViiK'liainlhmy:, IVilin-Wii-n, 1917, Uihan and Scliwar/.ciihfrj;. .S7((/r/», Gordon: Two Cases of Liinji Disease witli the Kiiianations from Tlioiiuin Nitrate, Brit. Med. Jour., Marcli, 1004, pp. ().')4 -<).")."). Sluitr, Jf. F.: Present Position of Treatment of Carcinoma of Cervix, P.rit. Mid. .Tonr., 1921, ii. 1101. Slmhcr, John B.: Emanation of Kadiinn Alisorl)ed and Retained l>y Cocoanut Cliar- June, 1920, i, ]ip. UlU-iiSO. Shine, F. W.: Case of Si>rinff Catarrh, Treated with Radium, New York Acad, of Med., Section on Ophthal., Arch. Ophthal., 1910, xxxix, 14.1. Shohcr, John B.: Emanation of Radium Alisorlied and Retained by Cocoanut Char- coal, Jour. Am. Med. Assn., Au<,nist 21, 1909, pp. (i24-r)28. Shoemaker, George Ervtxj: Primary Carcinoma of the Uretiira. Retention of Urine from Ohstruction. Restoration of Function l»y Radium, Surjj., Gynec. and Obst.. June, 191(i, xxii, 7r,0-7:n. Shumway. Edward A.: Vernal Conjunctivitis. Its Treatment liy Applicatimis of Ra- dium, Pennsylvania Med. Jour., 1919, xxii. 79.i-79.'j. Siehel, Gerald: A Case of Rodent Ulcer Treated witli Radium, Brit. ^[ed. Jour., Jan- uary, 1904, pp. 182-1 S.I. Riegel, P. W.: Dauererfolfje in der irvnjikidojrischen Radiotlicraiiie, Stralileiitlierapie, 1912, i. 4r,7-47(5. SicveTcing, H.: Die Radioaktivitiit der ]\[iiieral(iuelien. Berl. klin. Wdinschr.. 1900, No. 2.3, pp. 779-780. — Ucber Quellenmcssung, Strahlentherapie, 191.^, iii, 741-744. Sigwart, W.: Ueber die Riickbiidunjj der Bhisenverjin dcrungen bei liestrahlten Kob lumkarzinonun, Zentralbi. f. Gynjik., 191o, No. 4.1, pj). 1(54.")-1()4S. — and Jlan-diy, P.: Das Mesotliorium in der Gvniikologie, Med. Klin., 19i:i, No. ?,:\, pp. 1.322-1.326. Silbergleit, IT.: Ucber den Einfluss von Radiumemanations lialtijjer Badcr auf den Gaswechsel der Menschen, Berl. klin. Wclinsdir., 1908, No. 1, pp. 1.3-14. — Uel)er den Kinlluss von Radiuinemnnation auf den (iesamtstoffwechsel des AEenschen. Berl. klin. ■\Vclinschr., 1909. No. 2(5. jip. 120.1-1 20(5. .'''i7r(f McJlo, A. da: Ueber die Wirkunj; der Strahlenden Enerjjie auf das Blut und die Blutbildenden Oryane, Strahlentherapie, 191.1, vi, .387-:{97. Simmons. ChanmUig C: The Treatment of Carcinoma of the Skin with Radium. Tlie Results of the Cases Treated at the Collis P. Huntin^iton Memorial Hospital. Boston Med. and Surgr. Jour., 1919. clxxxi, 477-488. Simm^n^ls, M.: Ueber Mesothoriumschadijjunr der Ronttien- unil Radiumstrahleii, Strahlentheraj.ie, 191:'., ii, 192-22.3. Simpson, C. Angii.stna: The Relative Value of Radium and N-ray in Treatment of Skin Diseases and Cancer, South, ^[ed. Jour., Oct.iber. 19U, pp. 818-821. — The Effects of Radium ami X-ray on Cancer; Es|H'cialiy Skin Lesions of the Disease, A'ir;;inia Me9-377. 374 RADUM THERAPY — Eailiuni in the Treatment of Lvnipliangioma Ciix-umseriptuni, Jour. Am. Med. Assn., March 25, 1016, Ixvi, 9-19-9o0. — Radium Therapy — Remarks on the Use of Radium in Deep-seated Malignant Dis- eases and in Dermatolocry, Illinois Med. Jour., 1916, xxx, 123-126. — Radium in the Treatment of Cancer and A^irious Other Diseases of the Skin, Jour. Am. Med. Assn., Xovember 18, 1916, Ixvii, 1.508-1511. — Radium Therapy — Remarks ou the Present Status of Radiiim in Its Relation to A'arious Diseases, Especially Cancer, Radium Quarterly, January, 1917. — Radium in tlie Treatment of Chronic Lymphatic Leukemia, Radium Quarterly, - January, 1917. — Radium Therapy with Special Reference to the Use of Radium in Dermatology, Radium Quarterly, April, 1917. — Radium in Malignant Disease, Surg. Clin., Chicago, February, 1919, iii, No. 1, pp. 63-73. — Radium Tlierapy, Oxford Surgery, Sec. 14, v, 101-448. Hiredy, et al: Radium Treatment of Hemorrhagic Metritis, Gvnec. et Olist., Paris, iv, 482. — Radium Treatment of Uterine Filri-omas, Gynec. et Obst., Paris, 1921, iv, p. 427. Sl-eel, EoJand E.: The Earlv Diagnosis and Treatment of Cancer of the Cervix. Calif. State J. M. Xovember, 1921, p. -138. Sittenfield, M. J. : The Significance of the Lymphocyte in Immunity to Cancer, Jour. Cancer Research, April, 1917, ii, 151-157. Sl'orczewslci, JT., and Sohn. J.: L^eber den Einfluss der Radiumtherapie auf den Stoff- wechsel bei Gichtikern, Ztschr. f. exper. Path. u. Therap., xiv, Xo. 1, pp. 116- 134. Sluys, F.: Ein Fall von Makrocheilie, Strahlentherapie, 1914-1915, pp. 241-243. Smith, BelUnglwm E.: The Distribution and Excretion of Radium and Its Emanation after Internal Administration, Quart. Jour. Med., 1912, v, 249-264. Smitli, Harmon-: Papilloma of the Lar^nix, Jour. Am. Med. Assn., December 19, 1914, Ixiii, Xo. 25, pp. 2207-2211. Smith, B. L.: X-ray, Radium and Surgery in Treatment of Cancer, Xebraska Med. Jolir., September, 1921, vi,, 282. Snyder, F. K.: The Radical Cure of Cancer by Radium, Radium, December, 1915, vi, Xo. 3, pp. 59-60. Abstract of paper i>reseuted before Freeport Illinois Acad. of Med., September 20, 1915. SobotJcy, Irving: Radium Treatment of Tinnitus and Middle Ear Deafness, Xew York Med. Jour., June 16, 1917, cv, 1138-1139. Soddy, FrcderieTc : A Method of Applying the Rays from Radium and Thorium to the Treatment of Consumption, Brit. Med. Jour., July, 1903, pp. 197-199. — Die Xatur des Radiums, IJebers. von G. Siebert, Leipzig, 1909, J. A, Earth. — The Chemistry of the Radio-elements, London, 1911-1914, Longmans, Green and Co. — The Interpretation of Radium and the Structure of the Atom, 1920, Putnam's Sons. — and JlussrU, A. S.: The Gamma Ravs of Uranium and Radium, Philosophical Mag., 1909, xviii, 620-649. Sohlern: Ucber die Gicht und die Kissinger Trinkkur, iled. Klin., 1910, vi, Xo. 12, pp. 467-469. Soihtnd, Albert: Further Comments on Radioactivity, Am. Jour. Roentgenology, Feb- ruary, 1920, vii, 102-106. — An Interesting Case, Urol, and Cnlan. Rev., February, 1920, x-xiv, 103-104. — Cancer of tlie Lip, Urol, and Cutan. Rev., October, 1920, xxiv, 599-601. — Reaction to Radium and Roentgen Rays, Ann. Med., Xovember, 1920, i. 405. — Radium Element Versus Radium Emanation, Am. Jour. Roentgenology, December, 1920, vii, 612-614. — Therapeutic .\sppct of Irradiation in Superficial Malignancy, Jour. Am. Med. Assn., 1921,,lxxvii, 1560-1561. — Present Status of Radium Therapy in Female Pelvis, Jour. Radiology, January, 1921, ii, 40. — Economic Problems of Radium Therapy, Med. Rev. of Rev., February, 1921, xxvii, 79-81. — Present Problems and Future Pro.spccts of Deep Roentgen Therapy, Am. Jour. Roentgenology, May, 1921, viii, 276-279. — The Rationale of Radiation in the Female Pelvis, California State Jour. Med., Xoveml)er, 1921, p. 434. nir.i.iodKAi'iiY 375 Sotolcwsli, Ismar : Das fi'ttspaltciulo Fcnni'iit tics Blutserums unic, \9\5, vi, 419-442. Snmmcr, Fnint : Radium iiiid Radicr Loi.stinifr u. Fortsclir. a. d. Cudi. d. pliys. Mod., Leip/.i^r, 1908. — l^idiiT (>ino ncne Art der Tlicrapi'iitistdicn Anwcndiin^ der l^iusi't/.unn;.s])rodiK"to dcr Radioidonionte iii orstor Linie dor Radiiiniomanation, Ztsolir. f. expcr. Path. u. 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Wieprecht, Hans: Die Radioaktiven Eigensehaften einiger Solquellen nord- und Mit- teldeutschlands, Liaug.-Diss., Halle, 1909, Kaemmerer. Wilke, A.: UeV)er den Einfluss einiger physikalischer Heilmetlioden auf die Harn- saureausscheidung, Ztschr. f. phys. u. diatet. Therap., xiii, 430-438. ff'illins, G. C: Experiences witli Radium, Boston Med. and Surg. Jour., 1922 clxxxvi, 14. Willcins, II. F., and Gewin, TVm. €.: The Use of Radium in the Treatment of Menorr- hagia and Metrorrhagia, Radium, January, 1920, xiv, 77-80. — and — The Treatment of Cancer of the Lip with Radium, Urol, and Cutan. Rev., 1922, xxvi, 46-48. Wilkinson, Will: Radiotherapy of Glands, Southwestern Med., September, 1921, v, 6-14. WiUcnek, E. G. : The Action of the Rays from Radiiim upon Some Simple Forms of Animal Life, .lour. Pbysiol., 1904, xxx, 449-454. — The Action of Radium Rays on Tyrosinase, Jour. Physiol., 1906, xxxiv, 207-209. Williams, Francis, H.: Some of the Physical Proi^erties and Medical Uses of Radium Salts, Med. Xews, 1914, Ixxxiv,' 241-246. — Early Treatment of Some Superficial Cancers, Especially Epitheliomas by Pure Ra Prostate aner, 1!)21. p." SI 2. — Verucca X'ul^aris Treated with Radium, rrol. and Cutan. Rev., 1!»22, xxvi, ill. Z Zimmcni, .i.: Le radium, Pressi- med., l!l(l4. — Les Ac(|uisiti(Uis receiites en tdect roradidloiiie, Medicdne, Paris, JuiU', l!t21, ii, HfU- 67il. — , Cottenot, v., tuid P<(/i/J»r, A.: Die AVurzelliestrahlung (Radiotherapie radicidaire) zur Rehandlunji der Neuial;,nen (Isidiias, Plexus brachialis, Tiigemimis) usw., Strahleiitherapie, lt>l:{, ii, ()().')-(ii;;. — (Did Fdbrr, S.: A piojios de la peiu^tiatioii illaris capillitii. treatment of, 283 Dermatology, radium in, 245-296 Diabetes, treatment of, 320 Distance, as factor in radium technic, 119, 120, 124-129, 147 Dosage, radium ravs, deep effects, 129, 130, 133 139, 149, 152, 154, 155, 161 duration of exposure, 140-141, 143- 144, 155 for children, 117 frequencv of repetition, 150, 155, 160 ' intensive, 160 skin, permissible, 121-124, 155 tissues, previously treated, 106, 188 toxic, 315 x-rays, deep effects 137-139 (see also under names of disease and or- gans) Ductless glands, diseases, treatment of, 303-309 E Ear, (see Auditory Canal) Ectrojiion, treatment, 188 Eczema, chronic, treatment of, 286, 289 Edema, angioneurotic, use of radium for, 320 Electrometer, Wulf string, 50 Electrons, theory of rearrangement in ra- dioactive substance disintegra- tion, 27 Electroscope, use in measurement of, gamma ray activity, 35, 36, 51-53 Wilson tilted, 53, 54 Emanation, actinium, 20 radium (see Radium emanation) thorium, 20 Endometritis, treatment of, 244 Kpithelioma, diagnosis of, 160, 161 treatment of, basal cell, 161-188 cystic, 284 eyelid, 147 lip, 188, 189 mucous membrane, 149 nasal mucosa, 188 skin, 160-188 squamous cell, 160, 161 Epithelium, histologic effect of radium rays on, 78 Ervthrocvtes, as affected bv radium, 317, 318 as affected by thorium X, 317 Esophagus, radium treatment of, 151 carcinoma of, 205, 206 Ethmoiditis. chronic, treatment of, 298 Excessive radiation, results of, 100 Eve, effects of radium rays on, 85, 86 Eyeball, ]ihosphorescence produced in, 85 protection of, 147 F Fa ilia machine for cutting glass tubes, 113 method of distinguishing tubes, 112 modification of ajijiaratus for prepara- tion of radium emanation, 29 technic for inserting emanation am- poules, 156 IXOKX 387 Formeiits, effects of nuliuni rays on, Hii Filironivoina of uterus, treatment of, \Hl 244 Kilters {tice 8ereeus) ' Filtration of rays, 45 Finseii light, for lui>us vulgaris, 285 Fluorescenee, due to alalia rays, 71 Forcejis, for liaiuUing radium tubes, 147, 148, 323, 324 Simpson, 148, 324 "Fordyoe's disease," treatment of, 283 Freer apparatus for treatment of larynx, 205, 300-302 Freer needle holder, 15.3, 204, 211 G Gamma rays, ahsorption of, 43-44, 4(), 70 in water, 49-G8 activity, growth of, 33, 34 measurement of, 35, 36 effects, deep, 137-139 on tissues, 88, 89 on tumors, 90, 92, 93, 97 intensity of, 63, 125-129 ionization of, 42, 69, 118 jienetrability of, 70 jiroperties of, 41, 42 screens for, 46, 70, 88, 117, 118 secondary radiation from, 44 Goiter, treatment of, 83, 308, 309 Gout, treatment of, 319 H Hair, affected by radium rays, 295, 296 Heart, effect of radium treatment on, 313, 314, 320 Heat, in treatment of cancer, 199 Helium, atom given off from radium, 24, 26 Hemorrhage, after radiation, 96, 305, 30() myopathic, treatment of, 244 reduced, in leukemia, 305 Henry's law, 25 Herpes zoster, treatment of, 295 Hodgkin "s disease, treatment of, 308, 320 Hyperesthesia, use of radium, 295 llyperidrosis, treatment of, 295 Hy|rertricliosis, treatment of, 295 Hypertrophies, skin, treatment of, 294 tonsil, treatment of, 302 Idiosyncrasies, individual sensitiveness to radiations, 108 Immunity, i)roduced by radiation, 99-102 Inflammation, due to radium ravs, 75, 88, 1(13 105, 149, 245, 322 Inhalation of radium emanation, 311, 319 Injuries, professional, due to radium, 322- 324 Insufficient radiation, stimulation due to, 98, 99 Inti-nsity of g:iinma rays, 63, 125-129 radium rays, 49 Intensity of radium rays — Cont'd affected by secondary radiations, 139- 142 distance as varying, 119, 120, 124-129 x-rays, 49, 50, 137-139 Internal medicine, radium in, 310 321 Intenuitional Kadium Standard, 36 Intestines, carcinoma of, treatment, 206 Intratunioral radiations, 107 , 144, 145, 155-157 Ionization, effected by alpha rays, 69 beta rays, 69, 118 gamma rays, 42, 69, 118 radium rays, 89 Ionization chambers, use in absorption of radiations, 49, 50, 51, 52, 60, 66. 68 .Janeway dental modeling compound, 149, 189 Jolv and Stevenson, steel needles, 113 Keloids, treatment of, 246-257 Keratosis, treatment of, 294 Kidneys, efl"ect of radium rays on, 84 Laryngology, use of radium in, 298-302 Larynx, treatment for angioma, 299 carcinoma, 204, 205 papilloma, 298, 299 sarcoma, 230 technic of applications, 299-302 tuberculosis of, 299 Lecithin, theory, of cause of chemical changes in cells, 86 Leucocytes, effect of radium ravs on, 81, 304, 316 thorium X on, 316 observation of, during treatment, 102 Leukemia, radioactive deposit treatment, 320 radium ray treatment, 81, 303-308 lymph'atic, 304, 305 myelogenous, 303, 304 technic of, 306, 307 Leukemia cutis, treatment of, 294 Leukoiienia, brought on by exposure to radium rays, 323 Leukoplakia, treatment of, 189,198 Lichen chronicus simplex, treatment hangiomata, treatment with radium rays, 258, 275, 281 Lvniphatic glamls, effects of radium rays on, 80, 86, 87 388 INDEX Lvmphosarcoma, radioactive deposit treat- ment, 320 radium ray treatment, 230, 238, 239 M Malignant cells, effect of radium rays on, 79, 80, 90-102, 104, 145 ' Maxilla, inferior, carcinoma of, treatment, 199-202 superior, carcinoma of, treatment 199 Melanosarcoma, treatment of, 229 Menopause, due to radium treatment, 241, 243 . due to x-ray treatment, 242 Menorrliagia, treatment of, 244 Mesothorium, discoyery of, 18 Metabolism, effect of radium treatment on, 314, 315 Metastasis, treatment following, 160, 198- 202 Metritis, treatment of, 244 Metrorrhagia, treatment of, 244 Mica, "pleochroic halos" due to radio- actiyity, 72 ilicrocurie, defined, 36 Millicurie, a unit of measurement, 36 Millicurie hours, computation of, 141, 142 defined, 140 Milligram hours defined, 140 ]Molluscum contagiosum, treatment of. 284 Mouth, radium treatment of, 149, 189, 199 Muscle, effect of radium rays on, 83 Myalgia, treatment of, 319 Myopathic hemorrhage, treatment of, 244 N Nails, as affected by radium rays, 322 Nausea, due to radium reaction, 103 Needle holder. Freer, 153, 204, 211 Needles, containing radium emanation, 113, 114 containing radium salts, 109, 110 Joly and Stevenson, steel, 113 use in treatment of tumors, 144, 14."), loo, 156 Neryous symptoms, effect of radium rays 'on, 84, 85 Neuralgia, intercostal and sciatic, use of radium, 295 of trigeminus, 319 Neuritis, use of radium for, 295 Nevus, treatment with radium rays, 2.'')9 280 linear, 279, 283 pigmentosus, 268, 269, 276-278, 281 vascular, 266 Niton, 24 Noble gases, 24 Nose, sarcoma of, treatment, 188 O Otology, use of radium in, 298 Ovary, carcinoma of, treatment, 228 effect of radium rays on, 84 Packages, radium, preparation of, 153, 154 Pad, radium, 152-154 Pancreas, effect of radium rays on, 84 Papillomata, treatment of, 294 larynx, 298, 299 Parotid tumors, treatment of, 203-204 Penis, carcinoma of, treatment, 208 Phosphorescence, caused by radiation, 71 in eyeball, 85 Photographic action of radiation, 71 Pitchlilende, 21 Plaques, radium, therapeutic use of, 106, 110, 111, 124-130 use in epithelioma, 161 (see names of diseases and organs) Pleochroie halos (see Mica) Polonium, discovery of, 18 (see Eadium F) "Port-wine stains", treatment of, 273 Portals of entry, for insuring intensity below skin surface, 135-139, 152 Postoperative radiation, 159, 160, 189, 203, 204, 211, 212 Preoperative radium ti'eatment, 159, 160, 212 Proctitis, following radium treatment, 225 Prostate gland, carcinoma of, treatment, 209-211 Protactinium, 20 Protective devices, against radiations, 147, 323, 324 Pruritus, treatment of, 294 Psoriasis, treatment of, 286, 288 E RiKliation, technie of, 146-157 intratumoral 155-157 surface, deep radiations, 150-155 superficial radiations, 146-150 Radiations (see Absorption) effects of, chemical, 72 coloration, 71, 72 decomposition, 72 disintegration, 72 heat production, 70 ionization, 69 tluorescence caused liy, 71 light emitted by, 71 penetrability of, 69 70, 150- 152 plios[»horescence, caused by, 71 ]iliotographic action of, 71 projjerties of, 40 secondary, formed by screens, 48 produced by rays, 44 surface, 116, 117 Hadioactivp deposit, active change, 26 administration of, 311 collection, on foil, 114 on wire, 115 described, 26, 114 pathologic cft'ects of, 311 INDEX 389 Radioactive di'posit — Cunt \1 rate of decay, 1 1") slow cliaiigo, 26 solution of, 38, ;{!', 1 1 "> tlierapeutic use of, 2ti, I'T, 114, .'!l(i 313 Hadioactivo rays (sec Radiation and Ka- diiini Rays) Radioactive substances, defined, 40 period of decay, IS series descriljed, 19 transformation theory, 18, 27 Radioactivity, discovery of, 17 Radiographs, x-ray and made with ra diuni radiations, 71 Radiosensibility {see Sensitiveness to ir radiations) Radiothoriuni, discovery of, 18 Radium, administration of, 310, 311 analgesic action of, 2t>.j atomic weight, 22 chemical nature of, 22 content of various organs of budy, ;!12 decay, 24, period of, 18 disintegration, theory of, 27 effects of on tissues, morphoioi^ic, 31() physiologic, 313-315 elimination from body, 311-.'li;! extraction of, process, 22 in internal medicine, 310 321 metallic state, 22 occurrence in nature, 22, 23 origin of, 21 spectrum, 22 standard, international, 36 of various countries, 36 Radium A, a decay product of radium emanation, 25, 26 properties, 28 Railium B, described, 26 properties, 28 Radium C, described, 26 properties, 28 Radium C,, described, 26 Radium C„, desi-ribed, 26 pro|)erties, 28 Radium D, described, 26 properties, 28 Radium E, described, 26 projjerties, 28 Radium F, or jiolonium, 18, 2(5 eifect on skin, 88 l>roperties, 28 Radium G, atomic weight, 26, 27, 28 described, 26 properties, 28 Radium emanation, al)sorption of, by difl'erent substances, 24, 25 administration of, 311 activity of measurement, 35-38 atomic weight, 24 baths, 311 diemical behavior, 24 decay, 25 period of, 25, 34 Radium emanation — Cont 'd rate of, 33, 111 inhalation of, 311 preparation of, 2!)-3!», 111, 112 solution of, [(reparation, 38, 39 therapeutic use, 81 spectrum, 24 Radium ravs, effect of, biologic, 88-102, 149-150 ionizing, 42, 69, 89, 118 on animal life, lower forms, 74, 75 liigher forms, 75, 76 on bacteria, 73, 74 on blood, 80-82, 316-318 on blood pressure, 314, 320 on blood vessels, 82, 96 on bone nnirrow, 80, 86, 87 on brain, 85 on cartilage, 83 on cells, normal, 86, 87 on connective tissue, 81, 82 on eye, 85, 86 on ferments, 86 on lieart, 313, 314, 320 on kidneys, 84 on leucocytes, 81, 304, 316 on liver, 84 on lymi»hatic glands, 80, 86, 87 on muscle, 83 on nervous system, 84, 85 on ovary, 84 on pancreas, 84 on salivary glands, 84 on skin, 76 8U, 87, 127, 128, 155, 245 on spleen, 80, 81 on stomach, 83, 84 on testis, 84 on thyroid and thymus glands, 83 on vegetable life, 74 sterilizing, 93-94, 159 stimulating, on cells, 80, 93, 96, 98, 99 Radium salts, preparation of, 22 therapeutic use of, 22, 109, 310 Reaction, radium, amenorrhea, 242 due to intratunioral radiations, 107, 108 lUie to surface radiations, 103-106, 295, 296 following treatment of epithelioma, 189 of fibroids, 242, 243 of spleen, 307 inflammatorv, 75, 88, 103-105, 119, 245, 322 leidiopenia brought on, 323 menopause, 241-243 nausea, 103 ]diysiologic, 313. 322, 323 secondary or deferred, 106 selective, 104-245 telangiectasia, 105, 106, 269, 273, 295 Rectum, carcinoma of, treatment, 207, 208 radium treatment of, 149 390 INDEX Respiration, effect of radium treatment on, 314 Ehinology, use of radium in, 298 Rliinoscleronia, treatment of, 28(5 Ringworm, treatment of, 29o S Sagnac, Bays of, 48 Salivary glands, effects of radium rays 84 Sarcoma, treatment with radium rays, 228, 229, 232-239 treatment for, of bone, 236, 237 of larynx, 230 of mediastinal, 230, 232 of nose and nasopharynx, 188 of orbital tissue, 230 of periosteal, 230 of skin, 229 of- tonsil and postnasal space, 230 of vocal cord, 302 Scars, resulting from radium applica', 245 treatment of, 246-249 x-ray, treated with radium, 188 Screen holders, 149, 150 Screens for alpha rays, 45, 70 beta rays, 45-47, 70, 88, 117, 118 cosmetic applications, 245, 246 deep effects, 118, 120, 130, 143 eyeballs, protection of, 147 gamma rays, 46, 70, 88, 117, 118 plaques, 110, 111, 143 tandem, 151 treatment of angioma ta, 273, 274 carcinoma of bladder, 211, 212 of breast, 216 of cervix uteri, 225 of esophagus, 205, 206 of inferior maxilla, 202 of larynx, 205 of penis, 208 of prostate gland, 210, 211 • of rectum, 207, 208 of stomach and intestines, 206, of superior maxilla, 199 of thvroid gland, 203 of urethra, 208, 209 esophagus, 151, 205, 206 fibronivonia of uterus, 242, 243 keloids* 247-249 lupus erythematosus, 289, 294 lupus vulgaris, 285 metritis, 244 nevus, pigmented, 2S2, 283 sarcoma, 232, 233 skin, 77-79, 143 tuberculosis verrucosa cutis, 284, tumors, 91, 117 parotid, 204 various types, 46, 47, 150, 151 "window" 47 (see also names of diseases and or; treated) Sebaceous glands, use of radium for. on, 97. 207 285 fans 295 Selective absorption, defined, 104 Selective action, of radium rays, 104 Selective reaction, 104, 245 Sensitiveness to irradiations, carcinomata, 158-160 x-ravs, 159 malignant cells, 98, 101, 102, 104, 145 normal cells 104, 108, 145 Simpson ampoule inserting instrument, 153 Simpson forceps, 148, 324 Skin, dosage, permissible, 121-124, 155 effects of radium ravs on, 76-80, 87, 127- 128, 155, 2*45 histologic changes of, due to radium rays, 76-80, 127, 128, 245 treatment of, radium, 245-296 chronic infectious, 284-286 disorders of appendages of, 295, 296 hypertrophies, 294 inllammatory and granulomatous infiltrations, 286-294 neuroses, 294, 295 tumors, benign, 246 284 malignant, 160-202, 246 {see also names of diseases affecting skin) Spinthariscope, 71 Spleen, effects of radium ravs on, 80, 81, 86, 306, 307 of thorium X on, 80 protection from rays, 225 Springs, mineral, radium emanation con- tents of, 25 Sterilizing effects of radium rays, 93, 94, 159 Stimulation of cells by radium rays, 80, 93, 96, 98,. 99 Stomach, carcinoma of, treatment, 206 effect of radium rays on, 83, 84 Suprarenal gland, as effected liv thorium X, 317 Sweat glands, use of radium in treatment of, 295 Sycosis vidgaris, treatment of, 295, 296 Synovial lesion of skin, treatment of, 294 Syphilis, skin eniptions, treatment of, 280 Technic of radiation, 146-157 (see also names of diseases amenable to radiation) Telangiectasia, following radium treat- ment, 105, 106, 269, 273, 295 Temperature due to radium reaction, 103 Testis, carcinoma of, treatment, 228 effect of radium rays on, 84 Thermoluminescence, 71 Thorium, discoverv of radioactive 2)roper- ties of, 18 emanation, 20 Tiiorium series, atomic weights of, 19 period of decay of, 19 radiation from, 19 Thorium X, biologic action of, 88, 89, 310 effect on blood, 82, 310, 316, 317 INDEX 391 Thorium X, effect — Cout'd on spleen and other organs, 80 effects of huge injections of, ^1(5, 31S in treatment of anemia, 320 leukemia, 307 Thyroid gland, eidarged, treatment of, 309 Thvroid and thymus glands, carcinoma treatm'ent, 203 effect of radium rays on, 83 ''Tinnitus aurium, " treatment of, 298 Tissue, connective, effect of radium rays • on, 81, 82 Tissues, etfect of radium rays on, 77-80 malignant, treatment, 79, 80 Tobacco, as affecting leukoi)lakia, 189 Toiles, described, 110 use in treatment of nevus, 273 Tongue, carcinoma of, treatment, 198 Tonsil, carcinoma of, treatment, 198, 199 hypertrophy of, treatment, 302 sarcoma of, treatment, 230 Toxic doses of barium, 315 of radium, 315 Trachoma, treatment of, 297 Tuberculosis, of larynx, treatment of, 299 Tuberculosis verrucosa cutis, treatment of, 280, 281, 284-286 Tuberculosis adenitis, treatment of, 240 sinuses, treatment of, 240 Tubes, emanation, 112, 113, 124 130 "liare, " 112, 113 {sec also ampoules) for radium salts, 109, 110 Tumors, effect of radium ravs on, 89, 90- 92, 144, 145 intratunioral radiations, 107, 144, 14.", 155-157 screens in treatment for, 91, 117, 204 treatment of, 153-157, 158-lfiO brain, 233 malignant, inoi)erable, 159, 160 malignant, oiierable, 159 mediastinal, 230, 231 of eyelids, 234, 235 Tumors, treatment of — Cont'd, parotid, 203, 204 subcutaneous and subnmcous, 274-280 U I'raninite, deposits of, 21 Uranium, radioactive properties of, discov- ered, 18 radium content of, 21 Uranium series, atomic weights of, 20 period of decay of, 20 radiations from, 20 Urethra, carcinoma of, treatment, 208 Uterus, carcinonui of, treatment, 94, 150, 151, 221-227 Vagina, radium treatment of, 147 W'riuil conjunctivitis, treatment with ra- dioactive deposit, 114, 297 Vocal cord, sarcoma of, treatment, 302 Vulva, carcinoma of, treatment, 208 W Waters, mineral, radium emanation in, 25 Warts, treatment of, 294 X X-rays absorption of, 49, 50 discovery of, 17 effect on blood making organs, 86 immunity experiments with, 99, 101 keratosis, treatment of, 294 jienetrating power of, 44 radium treatment following use of, 188 reaction causing menopause, 242 scars treated with radium, 188 sensitiveness of carciiumiata to, 159 UNIVERSITY OF CALIFORNIA LIBRARY Los Angeles This book is DUE on the last date stamped below. 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