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RADIUM THERAPY

RADIUM THEBAPY

FRANK EDWARD SIMPSON, A.B, M.D.

PROFESSOR OF DERMATOLOGY, CHICAGO POLICLINIC; ADJUNCT CLINICAL PROFESSOR OF
DERMATOLOGY, NORTHWESTERN UNIVERSITY MEDICAL SCHOOL; ATTENDING DER-
MATOLOGIST TO MERCY HOSPITAL, ALKXIAN BKOTHEKS HOSPITAL, HENROTIN
HOSPITAL, ETC.; FORMER PRESIDENT AMERICAN RADIUM SOCIETY; FORMER
VICE CHAIRMAN, SECTION OF DERMATOLOGY AND SYPHILOLOGY,
AMERICAN MEDICAL ASSOCIATION; DIRECTOR OF THE FRANK
EDWARD SIMPSON RADIUM INSTITUTE.

WITH 166 ORIGINAL ENGRAVINGS

ST. LOUIS

C. V. MOSBY COMPANY

1922

COPYRIOHT, 1922, BY C. V. MOSBY COMPANY
(All rights reserved)

Printed in U. S. A.

Press of

The C. y. Mosby C
St. Louis

M. B. L. S.
MY WIFE

PREFACE

The completed manuscript of this book was {riven to the publishers
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, which I have
tried to make comprehensive rather than critical, indicates the wide-
spread interest in radium therapy. Unfortunately, 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 Miss 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 which 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 contruction 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
drawing of the electroscope. I wish to take this occasion to thank the
publishers for their kind and unfailing cooperation.

It is hoped that the book may be of interest, not only to those actually
engaged in radium therapy, but to all physicians, and that it may serve
as a reflex of the current practice in this branch of medicine.

F. E. S.

Cnir.\(io. M;m-h, 1922.

CONTENTS

CHAPTER I

PAGE

THE RADIOACTIVE SUBSTANCES 17

The Discovery of Radioactivity, 17 ; The Discovery of Polonium, Radium,
Mesothorium, Radiothorium and Ionium, 17; Transformation of the Radio-
active Substances, 18; The Radioactive Families, 19.

CHAPTER II

RADIUM — ITS ORHHN AND CHEMICAL NATURE 21

Origin, 21 ; Urauinito and Carnotite, 21 ; The Chemical Nature of Radium,
22; The Occurrence of Radium in Nature, 22.

CHAPTER III

BADIUM EMANATION AND RADIOACTIVE DEPOSIT 24

The Decay of Radium into Radium Emanation, 24; The Absorption of Ra-
dium Emanation by Different Substances, 24; The Decay of Radium Emana-
tion into Radioactive Deposit, 25; The Radioactive Deposit, 26.

CHAPTER IV

THE TECIINIC OF THE PREPARATION OF RADIUM EMANATION FOR THERAPEUTIC

USE AND THE METHOD OF MEASURING ITS GAMMA RAY ACTIVITY ... 29
The Preparation of the Emanation, 29; Measurement of the Gamma Ray
Activity of Emanation Tubes, 35.

CHAPTER V

THE RADIATIONS FROM RADIUM AND ITS DECAY PRODUCTS 40

Alpha Rays, 40; Beta Rays, 41; Gamma Rays, 41.

CHAPTER VI

ABSORPTION AND FILTRATION OF RAYS 43

Absorption of Rays, 43; Filtration of Rays, 45.

CHAPTER VII

THE ABSORPTION OF GAMMA RAYS IN WATER 49

First Observations of Intensities with First Type of lonization Chamber, 53;
Second Series of Observations with First Type of loni/.ation Chamber, 54;
First Observations of Intensities with the Second Type of lonization Cham-
ber, HO ; Second Series of Observations with the Second Type of lonization
Chamber, 04; Final Series of Observations with the Second Type of loniza-
tion Chamber, 66.

CHAPTER VIII

PHYSICAL AND CHEMICAL EFFECTS OF RADIUM RAYS 69

loni/.ation of Gases, 69; Penetration of Opaque Matter, 69; Production of
Heat, 70; Kmission of Light, 71; Phosphorescence and Fluorescence, 71;
Photographic Action, 71; Coloration of Various Substances, 71; Other
Chemical Kll'ects, 72.

10 CONTEXTS

OHAPTKR IX

PAGE

BIOLOGIC EFFECTS OF RADIUM RAYS 7.'!

Effects (if Radium Rays on Living Oils, "."> ; Effects of the Rays on the
Skin, 7(i; Kfl'ccts on the Spleen, Lymphatic Glands, :md Hone Marrow, Ml;
Kll'ects <ui (lie Blood, 80; Effects of the R:iys on Connective Tissue, Muscle,
mid Cartilage, S2 ; Kffccts i.f the R:iys on tile Tliyioid and Thynins (iliinds,
83; Effects of the Hays on the Stomach, Liver, Salivary Glands, 1'ancrease
and Kidneys, 83; Effects of the Rays on the Testis and Ovary, HI; KflVcis
of the Rays on the Xervons System, SI; Effects of the Rays on the Eye,
85; Effect on Blood-Making Organs, s<;: The Method of Action of Radium
Bays on Normal Cells, 86; Effects of the Different 'lypes of Rays, 88.

CHAPTEB X

BIOLOGIC EFFECTS OF RADIUM BAYS (Continued) 00

Effects of Radium Rays on Malignant Cells, 90; Effect of Rays on Human
Carcinoma, 92; The Method of Action of Radium Rays on Malignant Cell-.
97; 'The Question of Stimulation of Tumor Growth by Insufficient Radiation,
98. '

CHAPTEB XI

T&E RADIUM REACTION .103

Surface Radiations, 103 ; Intratuinoral Radiation, 107

CHAPTER XII

THERAPEUTIC APPARATUS . • 1M

Apparatus Containing Radium Salts, 109; Apparatus Containing Radium
Emanation, 111; Apparatus for Using the Radioactive Deposit, 114.

CHAPTER XIII

DOSAGE . . . 109

Surface Radiations, 116; Intratuinoral Radiations, 141.

CHAPTER XIV

THE TECHNIC OF RADIATION

Surface Radiations, 14ti; Intratuinoral Radiation. 1 .">.">.

CHAPTER XV

RADIUM IN GENERAL SUKGEKY 158

Malignant Tumors, 158; The Treatment of Carcinomata, 160; Sarcomata,
228; Benign Tumors, 240; Chronic Infections, 240.

CHAPTER XVI

RADIUM IN GYNECOLOGY

Malignant Tumors, 241; Benign Tumors, 241; Metritis and Endometritis,
244; Metrorrhagia and Menorrhajfia not Due to Cancer or Fibroid, 244;
Myopathic Hemorrhage, 244.

CHAPTER XVII

RADIUM IN DERMATOLOGY 245

Malignant Tumors, 24fi; Benign Tumors, 246; Chronic Infections, 284; In-
flammatory and Granulomatous Infiltrations of Uncertain Nature, 2S6;
Hypertrophies, 294; Neuroses of the Hkin, 294; Disorders of the Appendages
of the Skin, 295.

CONTENTS 11

CHAPTER XVIII

PAGE

K.MHI'M IX OlMlTII.U/MOLOfiY, OTOLOGY, RlIIXOIXXiY AND LARYNGOLOGY .... 297
Ophthalmology, 297; Otology, 298; Rhinology, 298; Laryngology, 2!)S.

CHAPTER XIX

RADIUM ix DISKASES or THE DUCTLESS <~!LAM»S 30.1

Leukemia, .'id.1',; Hodgkin's Disease (LynipliiKlcnonia). :!OS; Ooiter, :!OX ; Kn-
l.-n-c'.l Tliyimis Ol.-ui.l, ::n!i.

CHAPTER XX

KADIUM IN INTERNAL MEDICINE 310

The Administration nncl Elimination of Radium, .'ilO; Physiologic Effects of
Radium, 313; Morphologic Changes in the Tissue Caused by Radium, 31(i;
Therapeutic Indications, 318.

CHAPTER XXI

PROFESSIONAL INJURIES DUE TO RADIUM 322

l.w.-il Kllrrts, .",22; Constitutional Effects, :i22.

RIBLIOORAI'IIV
BIBLIOGRAPHY . .... 325

ILLUSTRATIONS

FIG. PAGE

1. Debierne-Duane-Failla apparatus 30

2. Diagrammatic plan of apparatus in Fig. 1 31

3. Diagram of electroscope 33

4. Diagram showing electrical connections for null method of using ionization

chamber 50

5. Diagram of first type of ionization chamber 51

6. Diagram of apparatus used for measuring absorption of gamma rays in water 52

7. Diagram of second type of ionization chamber . . . 53

8. Graph showing intensity in water. Base of applicator 3 cm. above surface 54

9. Graph showing intensity below surface of water. Base of applicator 6 cm.

above water 55

10. Graph showing field 5 cm. below surface of water. Base of applicator 1 cm.

above water 56

11. Graph showing field 10 cm. below surface of water. Base of applicator 1

cm. from water 57

12. Graph showing field 15 cm. below surface of water. Base of applicator 1

cm. from water I 58

13. Graph showing intensity on surface of water. Base of applicator 1 cm.

from water 50

14. Graph showing intensity on surface of water. Base of applicator 1 cm.

from water fiO

15. Graph showing field in air 61

16. Graph showing field in air, perpendicular to plane of tubes 62

17. Graph showing field in water, perpendicular to plane of tubes 64

18. Diagram showing change in intensity due to distance as compared with

change in intensity due to absorption in water 67

19. Apparatus for the application of radium 109

20. Appartus for the application of radium emanation 113

21. Diagram showing two radium tubes affecting three different points on skin 122

22. Graph illustrating Table XXVII 134

23. Diagram illustrating multiple portals of entry 136

24. Photograph showing the method of handling radium 146

25. Forceps 30 cm. long for handling radium tubes 147

26. Three pronged forceps 30 cm. long for handling radium tubes 147

27. Author's forceps for wrapping radium tubes in rubber dam 148

28. Screen holders • . 149

29. Same apparatus as in Fig. 28 but of smaller size 149

30. Flat silver screens with caps, devised for holding from 2 to 6 enamel emana-

tion tubes 150

31. Tandem gold screens for holding one or more enamel emanation tubes . . . 151

32. Platinum screen for containing a glass emanation tube 151

33. Screen for inserting radium tubes into the esophagus 151

34. Radium pad composed of "squares" of soft wood 152

35. Needle holder devised by Dr. O. T. Freer 153

36. Author's instrument, constructed on the plan of an ordinary syringe, for

burying emanation ampoules 153

37. Heavy cast-iron movable shield for the protection of the operator .... 154

38. Epithelioma of right cheek 162

39. Patient in Fig. 38 after radium treatment 163

40. Epitheliomia of right side of nose , 164

41. Patient in Fig. 40 after radium treatment 165

42. Epithelioma of tip of nose 166

43. Patient in Fig. 42 after radium treatment 167

44. Epithelioma of left lower eyelid 168

45. Patient in Fig. 44 after radium treatment 169

Hi. Epithelioma of right inner canthus, eyelids and nose 170

47. Patient in Fig. 46 after radium treatment 171

48. Epithelioma of left inner canthus, eyelids, nose, cheek, and upper lip . . . 172

49. Patient in Fig. 48 after radium treatment 173

50. Epithelioma of the right temple 174

51. Patient in Fig. 50, after radium treatment 175

14 ILI.rfsTKATIOXS

FIG. PACE

.",2. Kpithclioma of the left temple 176

53. Patient in Fit;. .">_ after radium treatment 177

54. Epithelioma of left malar region 173

55. Patient in Fig 54 after radium treatment 179

50. Epithelioma of forehead 180

57. Patient in Fig. 56 after radium treatment 181

58. Epithelioma of right ear 182

50. Patient in Fig. 58 after radium treatment 183

60. Epithelioma situated below right ear and involving ear lolie 1S4

(il. Patient in Fig. 60 after radium treatment 185

62. Kpithelioma of nose, left eyelid, cheek, and upper li| 186

63. Patient in Fig. 62 after indium treatment 187

64. Epithelioma of lower lip ]!)()

65. Patient in Fig. 64 after radium treatment . . : 191

66. Epithelioma of upper lip . . 192

67. Patient in Fig. 66 after ladium treatment 19!!

68. Epithelioma supervening on leukoplakia of right cheek . 194

6!l. Patient in Fig. (18 afler radium treatment 195

70. Carcinoma of the tongue in patient aged 6.1 years . 196

71. Patient in previous figure after insertion of 19 milHeuries of radium emana-

tion continued in 1~> bare glass ampoules 197

72. Carcinoma of right superior maxilla involving antrum 200

73. Patient in Fig. 72 after radium treatment 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.".

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 radiation 21 ">

SO. A part of Fi"'. 79 highly magnified 216

81. Same epithelioma as in Fig. 79, after radiation 217

82. A part of Fig. 81 highly magnified 21 *

83. Carcinoma of left breast 219

84. Patient in Fig. 83 showing improvement under radium treatment .... 220

85. Metatypic pavement cell opithelioma of the neck of the uterus. I'.efore

treatment 222

56. Same epithelioma as in Fig. 85. Fragment removed 10 days after the first

application of radium I'L'L'

87. Same epithelioma as in Fig. 85. Section removed on the 29th day after tTie

first radiation . . . 22.'!

88. Same epithelioma as in Fig. 85. Fragment removed from the surface of the

cicatrix of the neck of the uterus three months after first radiation . . 224

89. Polymorphous sarcoma with predominance of fusiform cells. Before radia-

tion 228

90. Same sarcoma as in Fig. 89. Section of large nodule removed 15 days

after powerful irradiations 229

91. Same sarcoma as in Fig. 89. After radiation 230

92. Sarcoma of right ear. Recurrence after excision 231

93. 1'atient in Fig. 92 after radium treatment 231

94. Sarcoma of left cheek in girl aged nineteen 232

95. Patient in Fig. 94 after radium treatment ...... 233

96. Tumors of eyelids 234

97. Patient in Fig. 96 after radium treatment 235

98. Sarcoma of bone. Recurrence after operation 236

99. Patient in Fig. 9S after indium treatment 237

100. Lymphosarcoma of neck 23S

101. Patient in Fig. 100 after radium treatment ... 239

102. Cicatricial keloid, following a burn of the face. Before radiation .... 246

103. Same keloid as in Fig. 102 after radiation 247

304. 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-iron 250

107. Patient in Fig. 106 after radium treatment 251

108. Keloid of back of neck. Recurrence after surgical removal 252

ILLUSTRATIONS 15

no. PAGE

109. Patient in Fig. 10$ after radium treatment 253

110. "Ac-no keloid" of hack of neck 254

111. Patient in Fig. 110 after radium treatment .... 255

112. Keloid of face following a burn 256

11)5. Patient in Fig. 112 after radium treatment . . . ' 257

114. Flat angioma of the hairy surface. Before radiation 258

115. Same angioma as in Fig. 114, after treatment with radium by the method of

"selective reaction," i.e., without visible macroscopic inflammation . . 25!)

516. Cavernous angioma of tip of nose 260

117. Patient in Fig. 116 after radium treatment 260

118. Cavernous angiomn of forehead 261

119. 'Patient in Fig. 118 after radium treatment 261

120. Cavernous angioma of lower lip 262

121. Patient in Fig. 120 after radium treatment 263

122. Flat angioma of side of face, neck, chin, and lower lip 264

123. Patient in Fig. 122 after radium treatment 265

124. Vascular nevus of face and neck 266

125. Patient in Fig. 124 after radium treatment 266

126. Angioma of side of face and head in patient aged six weeks ' 267

127. Patient in Fig. 126 at age of one and one-half years, after radium treatment 207

128. Slightly elevated angioma of side of face 2f>8

129. Patient in Fig. 128 after radium treatment 269

130. Angiosarcomn (?) of left arm 270

131. Patient in Fig. 130 after radium treatment 271

132. Large cutaneous and subcutaneous angioma of left side of neck in child

aged 6 months 272

133. Patient in Fig. 132 after radium treatment . . . . : 272

134. Lymphangioma circumscriptum of right buttock and inner surface of right

thigh .275

135. Patient in. Fig. 134 after radium treatment 275

136. Pigmented nevus of left lower eyelid and face 276

l.'i". Patient in Fig. 1:16 after -radium treatment 277

138. Pigmented hairy nevus of left eyebrow and forehead 278

139. Patient in Fig. 138 after radium treatment 27S

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 finger .... 280
li::. Patient in Fig. 142 after radium treatment 280

144. Tuberculosis verrucosa cutis of first phalanx of left thumb 281

145. Patient in Fig. 144 after radium treatment 281

146. 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 canthus 286

151. 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. Lupus erythcmatosus involving nose and cheeks 288

155. Patient in Fig. 154 after radium treatment 289

156.* Lupus erythematosus involving right cheek and upper lip 290

'57. Patient in Fig. 156 after radium treatment 291

15S. Lupus erythematosus of four years' duration 292

159. Patient in Fig. 158 after radium treatment 293

Hill. Sycosis viiljiaris '. 296

I'il. Patient in Fig. 16(1 after removal of hair with radium 296

162. The Freei- damp for the intralaryngeal application of radium 300

!<>::. The applicator held in the jaws of the Freer clamp with the screen contain-
ing radium emanation in the glottis as indicated by heavy dotted lines . 300

Hil. Apparatus for intralaryngeal radiation 301

lii"'. chronic lymphatic leukemia -"'"I

Ki(i. Patient in Fig. 165 showing remission of the disease' after radium treatment 305

RADIUM THERAPY

CHAPTER I
THE RADIOACTIVE SUBSTANCES

THE DISCOVERY OF RADIOACTIVITY

Soon after Roentgen's discovery in 1895 of the x-rays, several physi-
cists began to experiment with various substances to determine whether
similar rays might be emitted by chemical bodies spontaneously. Poin-
care suggested that the production of x-rays, which penetrated matter
opaque to ordinary light, might be connected with the phosphorescence
and fluorescence excited by the cathode rays in the glass of the vacuum
tube. It was natural at first, therefore, to examine substances that
fluoresced under the action of ordinary light. Prof. Henri Becquerel of
Paris soon found that the fluorescent salts of uranium emitted radiations
that passed through a thin layer of silver and affected a photographic
plate. It was at first supposed that the emission of these peculiar radia-
tions was in some way connected with the fluorescent properties exhibited
by some of the uranium compounds. Further experiments proved, how-
ever, that the nonfluorescent salts and the metal uranium itself, which
is also nonfluorescent, emitted the radiations. From this observation
Prof. Becquerel concluded that the rays were due to the element uranium
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.
Becquerel showed that uranium radiations like x-rays were capable of
discharging electrified bodies such as the electroscope. Rutherford, in
1899, demonstrated that this effect was due to the "ionization" of the
air in the electroscope by the radiations. This phenomenon will be re-
ferred to more fully in our description of the method of measuring the
gamma-ray activity of radium.

THE DISCOVERY OF POLONIUM, RADIUM, MESOTHORIUM
RADIOTHORIUM AND IONIUM

Using the electroscopic method of investigation, different physicists
then examined various other substances in order to determine whether
they were radioactive. G. C. Schmidt and Mine. Curie, working inde-

18 RADIUM THERAPY

pendently, discovered in 1898 that thorium, an element derived from
monazite and previously well known, .possessed radioactive properties.
M. and Mine. 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 were present in the ores. Their labors
finally resulted in the discovery of polonium which was named from
Mine. 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 pitchblende another radioactive
product which he called "actinium" and in 1905 Hahn isolated mesothor-
ium and radiothorium. Ionium was discovered in 1907 by Boltwood. Al-
together more than 30 radioactive substances arc now 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 bodies are transforming themselves so slowly that
no change in their radioactivity can be detected over a period of several
years. Their radioactivity, therefore, is relatively constant. To this
group belong uranium, ionium, radium and thorium. Other radioactive
bodies, of which mesothorium 2 and thorium X are examples, transform
themselves very quickly and cease to emit rays after a few hours or days.
The rate of transmutation is constant for any given substance, but differs
for the different radio-elements. The rate at which a substance decays
follows an exponential law; i.e., the rate at which a substance is decaying
at a given instant is proportional to the amount present at that instant.
It is this factor of proportionality that is constant for any particular
substance. The rate of loss of activity is usually spoken of in terms of
the "period," or more properly the "half decay period" both expres-
sions being used in an identical manner. The period of radium is ap-
proximately 1680 years. By this is meant that after 1680 years, one
half of the original number of atoms remains untransformed ; after 3360
years (2x1680) one fourth remains; after 5040 years (3x1680) one eighth
remains, and so on indefinitely. Radioactive transformations differ from
ordinary chemical reactions in that the rate of degeneration or change

RADIOACTIVE SUBSTANCES

of one radioactive substance into another cannot be altered by any known
physical or chemical means. The rate of transformation remains the
same throughout extremes of temperature and pressure. As each radio-
active substance transforms, it gives off radiations, which are of three
different kinds and are known as alpha, beta and gamma rays. These
will be described in a subsequent chapter.

THE RADIOACTIVE FAMILIES

At the present time, three parent substances are known — uranium,
actinium, and thorium — each of which transforms itself into a series of
substances until an end or stable product is reached. There are thus
formed three families or series of radioactive substances, viz., the ura-
nium series, the actinium series, and the thorium series. The knowledge
of the fact that actinium and its decay products are always present in
uranium minerals, leads to the belief that this product represents a small
fraction (3 per cent) of the "uranium 2" atoms which transform into
"uranium Y" rather than into ionium. We may interpolate a table at
this point showing the members of each series of radioactive bodies, the
rays each substance emits and its half value, i.e., the time required for
% of a given quantity to disappear by spontaneous transformation.

TABLK 1
URANIUM-RADIUM FAMILY

NAMK

ATOMIC
WEIGHT

HALF DECAY
PERIOD

RADIATION

I'l-aiiium I

238

5 billion years

alpha

Uranium X

234

24.6 minutes

betafgamma

Uranium X

234

1.15 minutes

beta+gamma

Uranium o

234

About 1,000,000 years

alpha

Ionium

230

About 100,000 years

alpha

Radium

226

1680 years

alpha

Radium Emanation (Niton)

222

3.85 .lays

alpha

Radium A

218

3 minutes

alpha

Kadium B

214

26.8 minutes

beta+gamma

Radium C

214

19.5 minutes

beta+gamma

(99.97%) (0.03%)

(alpha)

k.-icliiini C

210

1.4 minutes

beta+gamma

(side reaction 0.03%)

TCnd 0.03%

210

Radium C'

214

0.000001 seconds

alpha

(Main reaction 99.97%)

Radium D

210

16.5 years

soft beta

liudium K

210

5.0 days

soft beta

Radium F (Polonium)

210

136 days

alpha

Radium U (Knd Product)

206

No rays —

Atoms stable

RADIUM THERAPY

TABLE II
ACTINIUM FAMILY

NAME

ATOMIC

HALF DECAY

RADIATION

WEIGHT

PERIOD

u% of Uranium II

234

About 1,000,000 years

alpha

Uranium Y

230

1.5 days

beta

Protactinium

230

Estimated 1,200 to

alpha

180,000 years

Actinium

226

About 30 years

soft beta

Radioactinium

226

19.5 days

alpha

Actinium X

222

11.4 days

alpha

Actinium Emanation

218

3.9 seconds

alpha

Actinium A

214

0.002 seconds

alpha

Actinium B

210

36.1 minutes

beta+gamma

Actinium C

210

2.15 minutes

alpha

Actinium D

206

4.71 minutes

beta+gamma

End Product

206

TABLE III

THORIUM FAMILY

NAME

ATOMIC

HALF DECAY

RADIATION

WEIGHT

PERIOD

Thorium

232

23 billion years

alpha

Mesothorium

228

6.7 years

soft beta

Mesothorluai

228

6.2 hours

beta+gamma

Badiothorium

228

1.9 years

alpha

Thorium X

224

3.64 days

alpha

Thorium Emanation

220

54 seconds

alpha

Thorium A

216

0.14 seconds

alpha

Thorium B

212

10.6 hours

beta

(65% beta+gamma

Thorium GI

212

60 minutes

to ThC2

35% alpha to ThD

Thorium C, (Side Beaction)

212

Estimated 10'" seconds alpha

End

208

Thorium D (Main Reaction)

208

3.1 minutes

beta+gamma

End

208

CHAPTER II
RADIUM— ITS ORIGIN AND CHEMICAL NATURE

ORIGIN

Radium was first extracted by M. and Mme. Curie in the form of
radium bromide from pitchblende residues, obtained from St. Joach-
imsthal in Bohemia. It was subsequently found to be present not only in
all pitchblende ores, but also in all minerals containing uranium.

The work of McCoy, Boltwood and others has shown that in the very
old uranium minerals there is a strict proportion between the uranium
and radium content. For each 3,000,000 grams (three metric tons) of
metallic uranium there is one gram of metallic radium. This is very
strong corroborative evidence of the disintegration theory of Rutherford
and Soddy, according to which uranium is the parent of radium. In
uranium-containing minerals of more recent origin, the amount of
radium is 30 to 40 per cent less for the same amount of uranium than in
the older minerals. There is, however, no mineral or ore known, con-
'taining radium, which does not contain uranium.

URANINITE AND CARNOTITE

While many uranium-containing minerals are known, only two are
of practical importance. These are uraninite and carnotite. In these
ores, radium occurs in workable quantities.

Uraninite is found in Bohemia, Cornwall, Colorado and many other
localities. This mineral occurs chiefly in an amorphous modification
known as pitchblende, a dense black substance of variable composition
and therefore not to be described by a single chemical formula. Pitch-
blende is essentially an oxide of uranium and contains in varying quan-
tities nearly half of the known metals.

Carnotite is an ore of much greater practical importance than uraninite.
It is the chief substance from which radium is now obtained. Large
deposits of carnotite have been found in Colorado and Utah. In the "car-
notite belt" of Colorado it has been estimated that there are at least eight
in ill ion pounds of uranium. From this it has been estimated that there
may be extracted at least 1000 grams of radium element.

Carnotite (named from the French chemist Carnot) was first described
by two French mineralogists, Friedel and Cummenge, in 1899. It is a
bright yellow powder composed of very minute crystals. Its chemical com-
position is very complex, but, when pure, it appears to be a potassium uranyl
vanadate. It occurs in nature in sandstone formations. Average carnotite

22 KADir.M THKKAl'Y

siiiulstone contains about 1.5 per cent to 6 per cent T'.,OS and this yields
from 3.5 to 15 rag. of radium element per ton. The extraction of radium
from carnotite ore or from other minerals is a very complicated process.
For the separation of one gram of radium element, approximately 500
tons of chemicals and one thousand tons of coal are used. After a con-
siderable amount of mechanical preparation ( crushing of ore, etc.) and
chemical treatment, the radium and barium are isolated together as ra-
dium barium chloride. From barium the radium is separated filially in
the form of radium bromide, by a process of fractional crystallization.

From this salt, all the other salts (chloride, sulphate, carbonate, etc.)
are prepared. Radium bromide and radium chloride are soluble while the
sulphate and carbonate are insoluble in water.

In the radium solution contained in the glass flask from which radium
emanation is to be extracted for therapeutic purposes the radium is in
the form of soluble radium chloride.

For making the various therapeutic applicators (tubes, glazed plaques,
toiles, etc.) the insoluble radium sulphate is used.

THE CHEMICAL NATURE OF RADIUM

Radium is to be regarded as a chemical element (symbol Ra.) belong-
ing to the group of alkali earth metals, which comprises the elements
barium, strontium, calcium and magnesium.

Demarcay found that radium gave a new and characteristic bright
line spectrum similar to the spectra of barium, calcium and strontium.
Its atomic weight, as determined by Mine. Curie, is 22(>.45. In its chem-
ical behavior, radium is closely allied to barium, forming a series of
analogous salts (bromide, chloride, sulphate, carbonate, etc.). It differs
essentially from that element, however, in being radioactive. In general
properties, it is analogous to the metals of the alkaline earths.

It was not until 1910 that radium was isolated by Mine. Curie and
Debierne in a metallic state. It was then found to be a pure white metal
showing the radioactive properties that would be expected on the assump-
tion that radioactivity is an atomic phenomenon. It produced radium
emanation and its activity increased at the theoretic calculated rate.
Metallic radium changes quickly when exposed to the air. It reacts with
water, decomposing it into hydrogen with the production of radium
hydroxide.

THE OCCURRENCE OF RADIUM IN NATURE

Besides occurring in more or less concentrated form in various ores,
radium is found throughout the earth's crust as one of the most widely
distributed of substances. Strutt, Joly, Knocke, and others have de-
tected it in minute quantities in volcanic rocks and in sea and river
waters.

RADIUM — ORIGIN AND CHEMICAL NATURE 23

As to the natural occurrence of radium in the animal and vegetable
tissues, experiments have been made by Lazarus-Barlow, Becquerel and
others to determine this point. Evidence has been presented to show
that radium in very minute quantities, but detectable by the electro-
scope, exists in human tissues. Lazarus-Barlow has sought to show
that in human tissues affected by malignant disease a slightly larger
• quantity is present than in normal tissues. This hypothesis cannot be
considered as established, and 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 effects must also be considered.

Prof. Becquerel concluded that if radium or any other radioactive sub-
stance exists in plants, it is in such small quantities 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 giving rise to a series of substances. The first of these
substances is radium emanation — a gas known to chemists as "niton."
The amount of this gas that is found in equilibrium with one gram of ra-
dium is a definite quantity and is known as the "curie." This is the unit
of quantity and at standard temperature and pressure (0° C. and 760 mm.)
may be expressed either as a unit of volume or of weight. At standard
conditions, the volume of one curie is .63 cubic millimeters, and the
weight is 6.2 micrograms. It is the heaviest gas known, having a density
one hundred and eleven times that of hydrogen.

Chemically, radium emanation behaves as an inert gas, i.e., it forms no
chemical combinations. It may be regarded as an analogue of the other
"noble" gases, helium, neon, argon, krypton, and xenon.

Like radium itself, the emanation shows a characteristic spectrum, which
is quite distinct, however, from that of its parent, radium. At low tem-
peratures, the emanation can be condensed from the gas with which it is
mixed. At very low pressures, the emanation condenses at -150° C., the
temperature of liquid air. The boiling point at standard pressure is in
the neighborhood of -65° C., and it has been found that the emanation
cannot exist in the gaseous state below -71° C. Below this temperature,
marked changes are observed in the appearance of the emanation.

When the radium atom decays into the radium emanation atom, it gives
off an alpha particle, which is in reality a helium atom with a double
positive charge. Since the atomic weight of helium is 4, it follows that
the atomic weight of the emanation should be equal to the atomic weight of
radium minus that of helium, or 226 - 4=222. By actually weighing a
known volume of the pure gas, Gray and Ramsay obtained the value of
224, which is very close to the theoretical atomic weight.

THE ABSORPTION OF RADIUM EMANATION BY DIFFERENT

SUBSTANCES

Radium emanation may be absorbed to some extent by various solids,
especially porous substances such as charcoal and particularly by cocoa-
nut shell charcoal and platinum black.

RADIUM EMANATION AND RADIOACTIVE DEPOSIT 25

Liquids have varying powers of absorbing the emanation. Fresh water
absorbs more than salt water, while organic liquids absorb it more
readily than either.

It was found by Rausch von Traubenberg that if air containing emana-
tion was shaken up with water, the air and the water each soon contained
a definite proportion of the emanation. In this respect the emanation
follows Henry's law, for it is absorbed until a state of equilibrium is
reached between the pressure of the emanation in the water and in the
gas.

The term "coefficient of absorption" has been used to express the
extent to which the emanation is soluble in liquids. This term may be
defined as the ratio between the concentration of the emanation in the
liquid and in the gas after equilibrium has been reached. The value of
this coefficient may be determined experimentally by the method of von
Traubenberg, i.e., by shaking up the liquid and the gas containing the
emanation, and then measuring with the electroscope the relative
amounts of emanation in the liquid and in the gas. It has been found
that the coefficient of absorption decreases rapidly as the temperature
of the water rises, at least between the limits of 0° and 39° C. At room
temperature the coefficient has a value of .250 and at 37° C, a value of
.165. The variation of absorption of radium emanation with the tem-
perature of the water is of importance in connection with the emana-
tion content of natural spring waters at various health resorts in Eng-
land, Germany, the United States and other countries. The amount of
radium emanation in different springs varies between 1 and 30 millicuries
per million liters.

While claims have been put forward for the health-giving qualities
of the waters of certain resorts, no direct connection can really be traced
between the radium emanation in the springs and physiologic effects.
Definite biologic effects that have been observed to follow the thera-
peutic administration of radium emanation or radium salts are due to
quantities several million times greater than are to be found in any
known natural springs.

THE DECAY OF RADIUM EMANATION INTO RADIOACTIVE

DEPOSIT

Unlike the atoms of radium, which is a comparatively stable substance,
the radium emanation atoms are very unstable and decay at a rapid
rate to form atoms of a third substance known as Radium A. This
change follows a simple exponential law, the half value period of radium
emanation being 3.85 days. The transformation is thus so rapid that in
about thirty days practically all of a given quantity of radium emanation

26 RADII'M THKRAI'Y

will have decayed. Later we shall insert a table showing the rate of
decay of the emanation.

When the emanation atom transforms, it gives off an alpha particle or
ray. This particle is actually an atom of helium, which is also a gas.
The substance remaining is an atom of a solid known as Radium A.
Radium A in turn gives off an alpha particle and becomes Radium B.
Radium B gives off a beta particle and becomes Radium C. Radium C
in turn disintegrates but in a more complex manner than the other prod-
ucts. Radium C may transform itself in two ways. A very small propor-
tion gives off an alpha particle and becomes Radium ('._,. This latter sub-
stance is a branch product and so far as we know comes to an end quickly.
The remainder, and larger portion, of Radium C gives off beta and
gamma rays and becomes Radium C,, which in turn gives off an alpha
particle and becomes Radium I). Radium D gives off a beta ray and
becomes Radium E, and this product by loss of a beta ray transforms to
RaP, which is also known as polonium. Polonium then gives off an alpha
particle and becomes the end product of the series, or Radium G, a
substance chemically indistinguishable i'rom lead, but having an atomic
weight of 206 while the atomic weight of ordinary lead is 207.1.

THE RADIOACTIVE DEPOSIT

The series of substances from RaA to RaF constitutes the so-called
radioactive deposit. This latter term was derived from the fact that
these substances are deposited on the walls of the tube or other con-
tainer when the radium emanation, sealed in the tube, decays. The
radioactive deposit may be considered as being composed of two groups
of substances, the one group being known as that of "rapid change"
and the other group as that of "slow change." Radium A, B, C consti-
tute the radioactive deposit of rapid change, their half value periods
being 3 min., 26.7 min., and 19.5 min., respectively; radium D, E, and F
constitute the radioactive deposit of slow change, their half value pe-
riods being 16.5 years, 5 days, and 136 days respectively. The penetrating
radiations used therapeutic-ally are derived from the active deposit of
rapid change and especially from Radium C.

When a radium salt, such as radium sulphate, is sealed in a glass
tube, it is evident that the emanation which is forming continuously can-
not escape. At the same time the emanation is also disintegrating to
form the series of products just described. After a certain time (about
six weeks) the two processes have reached a stage at which the number
of radium atoms disintegrating per second to produce emanation atoms
equals the number of emanation atoms transforming to RaA. When
this takes place, the radium is said to be in equilibrium with its emana-
tion. It is not necessary, however, for the formation of the active de-

KADH'M EMANATION AND KAD1OACT1VK DEPOSIT 27

posit that the tube should contain radium at all. If the radium emana-
tion alone is introduced into the tube and the tube is sealed, the active
deposit is formed in precisely the same manner. When the emanation
has all decayed, the active deposit of course ceases to form and the
radioactivity of the tube is at an end so far as its therapeutic efficiency
is concerned. As a matter of fact, radium D, E and P are still contained
in the tube, but as their transformation is very slow, and as the gamma
rays produced by them are of feeble intensity, these products are not
of therapeutic interest so far as the local application of radium is con-
cerned.

The Atomic Disintegration Theory of Rutherford and Soddy

The disintegration theory of Rutherford and Soddy explains in a ra-
tional manner the transformation which radium and the other radio-
active substances undergo. According to this theory substances exist in
nature whose atoms, unlike those of most elements, are not stable but
are constantly undergoing spontaneous disintegration. These are known
as radioactive substances. The rapid disintegration or "explosion" of
the atoms of such substances results in a rearrangement of the electrons
composing the atoms. In a given time a certain definite proportion of
all the atoms of a radioactive substance becomes unstable and breaks
up. An alpha particle or ray or beta and gamma rays are given off in
the process of disintegration. In a few cases, as in the case of actinium,
which transmutes into radioactinium, disintegration of the atom appar-
ently takes place without rays being given off. There is chemical evidence
that leads to the belief that in these "rayless" changes there is really
emitted a low speed beta ray which because of its low velocity escapes
detection. When an alpha particle is given off, as a consequence of
the disintegration of the atom, the resulting atom is always lighter than
its predecessor and possesses different physical and chemical properties.
This is well illustrated by radium and its next transformation product,
radium emanation, which are strikingly dissimilar, as we have seen.

From this viewpoint, we may now consider the breaking up of the
radium atom to form the radium emanation atom, of the radium emana-
tion atom to form the atom of radium A, etc. In the radium series
there are 5 substances that give off alpha particles (helium atoms) as
they disintegrate. These are, in order of occurrence, Radium, Radium
emanation, Radium A, Radium 0, and Radium P. Assuming the atomic
weight of radium to be 226 and that of helium to be 4, the final atom
produced when Radium F disintegrates should have an atomic weight
of 226 less 20 (i.e.. 5 x 4) or 20fi. This is slightly less than the atomic
weight of lead and it is an isotope of this metal that is the final product
in the radium disintegration series. In Table IV this point is made
clear and certain other data are given for reference.

RADIUM THERAl'Y

TABLE IV

RADIUM ATOMIC
SERIES WEIGHT

\VKIGHT I'EU
GRAM OP
RADIUM

HALF-VALUE
PERIOD

RADIATION

KANGE OF
ALl'HA RAYS
AT 15° C.

Radium
\ Radium
^Emanation
Radium A
Bad him B
Radium C

Radium C
Radium D
Radium E
Radium F
Radium G
(End Product)

226
222

218
214
214

210
210
210
206

1 gram
5.7x10-6 gram

3.1x10-9 gram
2.7x10-8 gram
2.0x10-8 gram

1680 years
3.85 days

3.0 minutes
J<>.8 minutes
]9..j minutes

1.4 minutes
li>."> years
5.0 days
136 days

alpha
alpha

alpha
beta+gamma
beta+gamma
(alpha)
beta+gamma
soft beta
soft beta
alpha

3.30 cm.
4.16 cm.
4.75 cm.

6.57 cm.

8.6x10-3 gram
7.1x10-6 grain
1.9xlO-< gram

3.77 cm.
No rays
Atoms stable

CHAPTER IV

THE TECHNIC OF THE PREPARATION OF RADIUM EMANATION
FOR THERAPEUTIC USE AND THE METHOD OF MEAS-
URING ITS GAMMA RAY ACTIVITY

THE PREPARATION OF THE EMANATION

Radium emanation in tubes or applicators instead of the radium itself
as a source of therapeutic radiations appears to have been used first in
1912 by the London Radium Institute. The Debierne-Duane apparatus
(Fig. 1) as modified by Failla of New 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 physicists. The first pump draws the accumu-
lated gases from the flask containing the radium solution and introduces
them into the purification chamber. The second pump withdraws the
purified emanation and concentrates it in a capillary glass 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 hydrochloric
acid to prevent precipitation of the salt. From a practical point of
view not less than % gram of radium element can be utilized economically
in this manner.

The glass flask containing the radium solution is kept in a suitable
safe, and rests in a porcelain 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 (1, Fig. 2) to the pumping system
of the emanation apparatus as shown in Fig. 2.

Vessel 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 this vessel it would cover the walls with the active deposit
and since the surface of the vessel is quite large, the operator 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 only gas formed in the solution. The radium rays, continually
bombarding the water molecules, cause a decomposition of the water
into its constituents, hydrogen and oxygen. These two gases form by
far the largest part of all the gases produced. The total volume of all
the different gases is many times the volume of the emanation. In order
to concentrate the emanation into a small volume at a pressure of, e.g.,
20 cm. of mercury, the foreign gases must, for the most part, be removed.
In order to accomplish this, all the gases in the radium flask are pumped

RADIl'M THERAPY

over into the purification chamber !t, JO, and //. Fig. 2. Here the sodium
hydroxide (9), and phosphorus pentoxide (11) absorb carbon dioxide,
moisture, etc., while the heated copper oxide spiral (10) causes the hydro-

Fig. 1. — Photograph of Debierne-Duane-Failia apparatus. The photograph shows the single
type of apparatus. The duplex- type is usually installed so that either side of the system may be
available in case of accident.

gen and oxygen to recombine. The purified 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 capillary glass tube 18. The distal portion

PBEPABATION OF RADIUM EMANATION

(1 or more cm., e. g.) of this tube containing the concentrated emana-
tion is then cut off by a minute gas 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 opened in order to create a vacuum in the line 8-22 above the
mercury in vessel 7. Stopcock 6 is now opened and the mercury in •/
falls to the level in 7 . This allows the emanation, hydrogen, oxygen,
ozone and water vapor to come out of the radium flask through tube 1 and
to fill 4 by diffusion. Cock 22 is now turned to permit air to enter the
line 8-22 through the drying tube 23 containing calcium chloride. This
forces the mercury up in 4, driving the gases ahead of it and past the

Fig. 2. — Diagrammatic plan of apparatus in Kig. 1.

trap !> into the purification chamber (9, 10 and 11}. Cock 22 is again
turned to connect the line 8-22 with the auxiliary pump and the mercury
in / again falls, allowing another portion of the accumulated gases to fill the
bulb. The mercury in trap .? prevents the backward passage of gases
from !>, 10, 11 to /. This procedure of filling 4 with the gases and forc-
ing them ii]) past the trap .? into the purification chamber is repeated
until all the gases are pumped over. The completion of the process is
easily detected by the fact that when there is no gas present, the rising
mercury in / produces a sharp metallic click when it strikes the mercury
in trap .?.

Mefore the pumping process just described is started, the purification
chamber (fl, 10 and //) is tested to insure the existence therein of a good

32 RADIUM THERAPY

vacuum. If gases are found to be present, they are pumped through 16
and 17 into 26 by means of the mercury pump 12, 13, 14 and 15. From
there they may be exhausted into the room through 24 by the auxiliary
. pump and thence out of the room by means of a ventilating fan.

When a high vacuum has been established in the purification chamber,
an electric current is sent through the copper oxide coil 10, the strength
of this current being just sufficient to bring the coil to a low dull-red
heat. When the coil is hot, the purification chamber is ready to receive
the gases from 4. As they meet the hot coil, the hydrogen and oxygen
reunite and form water which is immediately absorbed by the phos-
phorus pentoxide (P.,0.,) contained in 11. By this action most of the
gas entering the purification chamber is eliminated. Tf any carbon
dioxide, chlorine or hydrogen chloride are present, they are absorbed
by the sodium hydroxide in 9. 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 few 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 be 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 now turned to connect line 8-22 with atmos-
pheric pressure. This causes the mercury to rise 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
14 and 16 are then closed. Line 8-22 is again exhausted, stopcock 14 is
reopened, and the mercury falls out of 12 which is again filled with
emanation. In this manner practically all of the emanation may be
pumped over into 17.

When the mercury has been raised in 12 for the last time it is allowed
to pass through 16 and up to 17. The emanation is then forced by means
of the mercury in 21, by opening stopcock 20, into the capillary tube 18.
The mercury rises in the capillary and when the desired concentration
is effected, stopcock 20 is closed. The capillary glass tube is about 1
millimeter in diameter, and can be sealed off very readily by means of a
small pin-hole gas flame. The part of the capillary tube sealed off con-
taining all the emanation is then divided by means of the same flame
into as many pieces as are desired. In this manner, any percentage of
the total amount of emanation is obtained for use in a small tube, of,
e.g., 1 centimeter length. These small glass tubes are then inserted into

PREPARATION OF RADIUM EMANATION 33

TABLE V

SlIOWIN-G THE KlSE OF GAMMA RAY ACTIVITY DUE TO RAC THROUGH 2 CM. OF LEAD

TIME

ACTIVITY OF AN EMANATION TUBE MEASURED IN
PERCENTAGE OF MAXIMUM VALUE:

min

.025

1 1

.32

1.90

1 1

8.9

( t

19.0

< i

30.0

< *

41.2

1 1

51.3

hr. 30 min.

.74.4

< «

87.8

" 30 min.

94.7

1 1

98.0

1 1

99.9

enameled silver tubes the ends of which are blocked with paraffine.
They are then set aside for 3% hours before their activity is measured.
The next day the same procedure is repeated in order to withdraw and
concentrate the emanation which has accumulated in the preceding 24
hours.

When the emanation is first admitted to the capillary tube its activity,
measured by the penetrating rays, is zero. As the emanation decays,

TABLE VI

SHOWING THE

TIME

RATE OF DECAY OF RADIUM EMANATION
PERCENTAGE OF MAXIMUM ACTIVITY (THEORETICAL)

100.00

1 lir.

99.25

2 hrs.

98.51

3 "

97.77

4 "

97.04

5 "

96.32

6 "

95.60

12 "

91.39

1 day
2 days
3 "

83.53
69.77
58.27

4 "

48.68

5 "

40.66

6 "

33.96

1 week

28.37

2 weeks

8.05

3 "

2.28

4 «

0.647

10 "

0.000337

RADIUM THKRAPY

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 about 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 reached, the activity of the tube begins to decay with the
same "time period" as that of the emanation. In other words,
16 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 shows 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
RADITM EMANATION DECAY TABLE

•27

2.1!

PREPARATION OF RADIUM EMANATION

hand vertical column. A tube having a strength of 78 me. decays each
twenty four hours as follows — 66 inc., 54 me., 45 me., i.e., reading horizon-
tally to the right. By finding 45 in the second single vertical column the
values for the following three' days are found to be 38 me., 31 me., 26
me. By finding 26 in the third single vertical column the values of this
tube for the following three days are found to be 22 me., 18 me., 15 me.,
and so on.

MEASUREMENT OF THE GAMMA RAY ACTIVITY OF EMANA-
TION TUBES

The measurement of the activity of the emanation tubes is made after
they have reached their approximate maximum strength. The measure-
ment is most easily and accurately done by means of the gold leaf electro-
scope. A diagram of this instrument is shown in Fig. 3.

Fig. 3. — Diagram of electroscope.

A is a plate of lead 1 centimeter thick used to eliminate all of the easily
absorbable rays. K 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 horizontal position being thus brought into the field of the
microscope, D.

In order to measure the quantity of a radioactive substance in a small
capillary tubo, the latter is placed in the V-shaped holder at E. The
penetrating gamma rays then pass through the lead plate, A, into the
electroscope, B, and the air in the electroscope is thus made a conductor
of electricity. This is known as "ionizing" the air. In other words, 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 itself. The negative charges will thus neutralize
a part of the positive charges of the leaf. The leaf will then tend to come

36 RADIUM THERAPY

nearer into the uncharged or vertical position and will thus move across
the field of the 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 the 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 was prepared my Mme. Curie in 1910 at the request of
the Brussels Congress of Radiology and Electricity. 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-
lows: 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, Vinoo 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 miorocurie is Viooo 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
when 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
gold leaf across the scale of the microscope. Therefore in order to measure
an unknown quantity of emanation it is only necessary to obtain the relative
rates of fall of the gold leaf when the "standard tube" is used and when the
"capillary emanation tube" is used and multiply this ratio by the number
of milligrams of radium element used as the "standard." If the activities
of the standard and the emanation tube are of very different magnitudes,
the natural leak of the electroscope must be taken into account in calcu-
lating the activity of the emanation.

If for any reason the error due to natural leak is not considered great
enough to affect seriously the result, the following simple formula is used
as a basis for the calculations involved.

K = 8-r- where

PREPARATION OP RADIUM EMANATION 37

' .E = activity of emanation tube.

s = activity of standard.

a = time of passage of leaf over any desired number of scale divi-
sions under action of standard.

6 = time of passage over same number of scale divisions under action
of emanation tube.

Let us suppose, for example, that we have as a "standard" a tube con-
taining 15 milligrams of radium element (the activity being therefore
equivalent to that of 15 millicuries), and an unknown 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 substituted for the "standard" and a similar ob-
servation taken. We will assume the time in this case to be 50 seconds
• (6). Substituting in the above formula the values of s, a and 6 which are

now known we find E = 15 y— -= 18 me.

It will be observed that, within certain limits, the distance of the
"standard" and the emanation tube from 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 dependable 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 number 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 the results, allowance for this must be made in
the calculations. In this case the formula takes the form :

aft
a- —

<ib
b

Here c is the time taken by the leaf when no tube is present .in passing
over the number of scale divisions chosen for the readings. Let us sup-
pose, ;is is the c:-ise in our laboratory, that this is of the order of 25 min-
utes; the formula then becomes:

38 RADIUM THERAPY

ab CO X 50
~c~ 25 X 60 ~

fiO-2

=18.13

_
50-2

This error (.13) (less than 1 per cent) for many purposes is negligible,
at least in small tubes, and, as a rule, in 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 would 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

60
E = 15 X _ =90 (uncorrected)

ab 60 X 10
~~c~— 25 X 60 ~

60 -.4

=93.12

-
10- .4

This would lead to an error of considerably over 3 per cent if the correction
were not applied.

The 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 deposited 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 manner. When the tube is cut off and the foil
carefully removed, its activity may be measured by means of a gamma
ray instrument. As in the case of the emanation, the unit of quantity
is the millicurie. This foil may be used as a uniform source of radiation
of short duration.

When a radioactive solution is required for injection into the blood,
it may be prepared in the following manner: A small amount of common
salt (NaCl) is packed into a small glass bulb. This bulb is heated in
a gas flame in order to thoroughly dry the salt, and is then sealed to the
emanation apparatus at 17 (see Fig. 2) just as in the preparation of
active deposit on the lead foil. After the air is pumped out, the purified

PREPARATION OF RADIUM EMANATION 39

emanation is forced into the salt, by means of mercury raised to the
small bulb. In 3 or 4 hours, when the maximum amount of active deposit
has formed and collected on the salt grains, the mercury is lowered again.
The emanation is allowed to pass into another part of the apparatus to
be collected in the usual way. The bulb is then cut off and distilled
water is forced in with a hypodermic syringe in sufficient amount to
make approximately a normal physiological salt solution. The "active"
water is subsequently withdrawn in the syringe.

As in the former case, the amount of active deposit in the syringe
is determined by the gamma-ray 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 difference in these 2 values. Proper
allowance for the decay of the active deposit must be made.

CHAPTER V

TIIK RADIATIONS FROM RADIUM AND ITS DECAY PRODUCTS

Rutherford states that from a theoretical standpoint it is desirable
to restrict thp term "radioactive" to substances that undergo spontaneous
atomic transformation. From this point of view, a few substances may
be said to be radioactive which apparently emit no radiations at all but
which do transform themselves spontaneously and give rise to new sub-
stances. From our present standpoint, however, we may fairly delinr
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 arc 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 three different kinds of radiations emitted by the radio-
active substances. These are known as alpha, beta, and gamma rays.
The table previously given (see list of radioactive substances) will suffice
to make clear the particular ray that each of the products emits.

It will be helpful to describe at this point the properties of the different
kinds of rays.

Alpha Rays

Alpha rays are material particles having a double positive charge and
a mass four times that of the hydrogen atom. In fact, they are merely
positively charged helium atoms shot out from the radium atom, as it
transmutes, with an initial velocity 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

RADIATIONS FROM KADir.M AND ITS DECAY PRODUCTS 41

of the radioactive substances can travel in air, depends upon its initial
velocity and the temperature and pressure of the air. For an alpha
particle of radium in air at standard conditions of temperature and
pressure, the range is 3.3 cm. In other words, the alpha rays of radium
are completely absorbed or stopped by 3.3 cm. of air and beyond this
distance their characteristic effects cannot be detected. Alpha rays
are analogous to the canal rays of a Crookes tube, and like them may be
deflected slightly by a very powerful magnetic field. While usually re-
ferred to as alpha rays, the term alpha particle is perhaps preferable.

A gram of radium in equilibrium with its decay products, Ra Emana-
tion, Ra A, B, and C, emits energy with its rays at the rate of 136 calories
per hour. Of this energy 125 calories are borne by the alpha rays, 4.5
Calories by the beta rays and 6.5 calories by the gamma rays.

Beta Rays

Beta rays are swiftly moving, negatively charged electrons and are
identical in type with the negatively charged particles constituting the
cathode rays of the f'rookes tube. They are about %S40 the mass of the
hydrogen atom. Soft, medium and hard beta particles may be dis-
tinguished according to their velocity and power of penetration. The
slowest beta particles are comparable to alpha rays in penetrating power
and are known as soft beta rays. The swiftest beta particles have about
the velocity of light and have one hundred times the penetrating power
of alpha rays. These are known as hard beta rays. The velocity of the
hard beta rays from Ra C is 96 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 2,000,000 volts (approximately a 16 foot spark
in air). Between the softest and hardest beta rays there is a series of
so-called medium beta rays, which are intermediate in their power of
penetration. The beta rays derived from Radium B and 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 opposite direction to the deviation of the alpha rays
because the beta ray is the negative electron. Beta rays are also de-
llccted much more than alpha rays because their mass is very much less
than that of the latter. As we have previously mentioned in the case
of the "alpha rays," the term "beta particle'' is preferable. In defer-
ence to custom, however, the term "beta ray" is retained.

Gamma Rays

These are undulations of the ether, or electro-magnetic waves, and are
similar to x-rays, except that their wave length is much shorter than
that of the latter. The velocity of the gamma rays is the same as that
of light.

42 RADIUM THERAPY

The production of gamma rays is due to the very intense electronic vibra-
tions which are set up 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.1' This phenomenon of energy transfer from a wave
to a particle has a very good analogy which is familiar to most of us in
the sound vibrations which 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 with 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 vibration, 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 differ-
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
than beta rays, and consequently have a smaller ioni/ing power. The
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
by a magnet.

CHAPTER VI

ABSORPTION AND FILTRATION OP RAYS

We have already referred to the fact that the radiations are capable
of penetrating opaque matter in varying degrees, certain types of rays
being easily absorbed while other types are stopped with the greatest
difficulty. In this chapter we shall consider some of the practical ad-
vantages of filtering or absorbing certain types of rays by means of screens.

ABSORPTION OF RAYS
Alpha Rays

It has already been stated that the alpha rays from radium are very
easily absorbed. The glass wall of the emanation tube, a sheet of note
paper, the film of a soap bubble or 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 by 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, % of the original amount of
rays will be unabsorbed after passing through 0.4 cm. of aluminum, %
of the original amount will be unabsorbed after passing through 0.6
cm., and so on until complete absorption. As we have stated before, the
beta rays are heterogenous and 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 93.8 per cent by 1 cm. of epithelial
tissue. Their intensity after passing through 1 cm. of epithelial tissue,
is. therefore, only 6.2 per cent of that exhibited at the surface of the
skin. This estimation does not take into account the diminution of in-
tensity due to divergence of the rays with distance from the source. The
intensity of the beta radiations from radium C is reduced to % the
initial intensity after passing through 17 meters of air, at ordinary room
temperature and atmospheric pressure.

Gamma Rays

The hard gamma rays 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

44 RADIUM TIIKKAPV

are absorbed approximately in accordance with an exponential law. This
law is followed, however, only in the event of the rays being allowed to
pass first through 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 cm. of water will absorb % 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 Il5 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 briefly 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 correspond to the characteristic x-rays for the par-
ticular element, and the higher the atomic weight of the element, the
more 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 and the thickness of the material that is radiated.
(c) When the primary gamma rays from radium strike matter, a part of
the original beam is scattered in all directions although the quality of the
beam "is not altered. Just as in the case of the primary beta rays second-
ary radiations are also set up by the primary gamma rays. These con-
sist of secondary gamma rays and secondary rays of the beta ray type.
Our knowledge of the secondary gamma rays is very imperfect. The
secondary beta rays have a penetrating power that is nearly equivalent
to that of the primary beta rays. When heavy elements such as lead

ABSORPTION AND FILTRATION OF RAYS 45

are impinged upon by gamma rays the secondary beta radiation is some-
what more penetrating than when lighter elements 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, Degrais and
Dominiei were apparently the first to use and advocate the employment
of rays obtained by filtration. By interposing between the radioactive
substance and the tissue to be treated, various metallic and nonmetallic
materials, the less penetrating 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 absorb by means of screens the undesirable types of
rays before they reach the skin, allowing only the more penetrating rays
to pass through the screen and affect 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 absorb the alpha rays we may theoretically place between
the radium and the skin a screen of %00 millimeter of aluminum or a
sheet of writing paper. In 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 !)!) per cent of the beta rays. One may 'thus use nearly
pure gamma rays, which will not be absorbed but will pass through the
screen. "When massive doses of deeply penetrating rays are used, it is
desirable to absorb 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 absorb or 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 applicators may be de-
scribed here. Screens are ordinarily made of silver, gold, platinum,
brass, lead or aluminum. For external applications, brass or silver
screens answer almost every purpose. It is believed that 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 the effects of radium on the tissues.

RADIUM THERAPY

When treating the interior 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 distance 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 3 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 Vioi ''Mo, 1, and 2 mm. thick.

Platinum %o and %n mm. thick.

Aluminum ' %00, %00, %n mm. thick.

Brass %0, 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 will 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 table it is an easy matter to calculate
the thickness of different materials which would be required to absorb

TABLE VIII

KAY ABSORBING

SUBSTANCE :

DENSITY THICKNESS REQUIRED

(APPROXIMATE) TO ABSORB 50% or

THE HARD BETA RAYS

THICKNESS REQUIRED TO
ABSORB 99.9% OF THE
HARD BETA RAYS

Gum rubber

1.0

1.00 mm. .

8.50

mm.

Water

1.0

1.00 "

8.50

* <

Soft tissues

1.0

1.00 "

8.50

1 1

Bone

1.7-2.0

0.60 ' '

5.00

1 1

Common glass

2.6

0.40 ' '

3.30

Aluminum

2.7

0.40 ' '

3.20*

1 1

Steel

7.7

0.14 "

1.15

( t

Brass

8.5

0.13 "

1.10

1 1

Nickel

8.7

0.13 "

1.10

( t

Silver

10.6

0.10 "

0.80

1 1

Lead

11.3

0.10 "

0.80

1 1

Gold

19.3

0.06 '

0.50

1 1

Platinum

21.5

0.05 ' '

0.40

1 1

ABSORPTION AND FILTRATION OF RAYS 47

a given amount of the hard beta rays. Let us suppose, e.g., that we
wish to use a series of brass screens which would equal %0 mm., %0 mm.,
1 mm., and 2 mm., of silver. A simple calculation of the relative density
of the metals shows that brass screens equivalent to silver screens of

1 C\ C

the above thicknesses, must be-^- of %0 mm., %0 mm., 1 mm., and 2

o.o

mm.: i.e., approximately % 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

THICKNESS OF
SILVER SCREEN

PER CENT OF HARD
BETA RAYS ABSORBED

PER CENT OF HARD
BETA RAYS LEFT

0.1 mm.

50.

0.2 "

75.

25.

0.3 "

87.50

12.50

0.4 "

93.75

6.25

0.5 "

96.88

.3.12

0.6 "

98.44

1.56

0.7 "

99.22

0.78

0.8 "

99.61

0.39

0.9 "

99.81

0.19

1.0 "

99.91

0.09

Upon examining the table it may be seen that the percentage of
absorption by a given thickness of the metal follows an exponential
law; i.e., if 50 per cent of the hard beta rays remain nnabsorbed after
passing through 0.1 mm. of silver, % of the original amount will remain
unabsorbed after passing through 0.2 mm., % of the original amount
will remain unabsorbed after passing through 0.3 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 different shapes and sizes
may be required. For the glazed plaques, pieces of metal of the material
and thickness desired may be cut to fit the face of the apparatus. The
metal screens may be round or square or of any other shape desired.
While they may be made 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 THK1; U^

Secondary Radiations

In the practical use of screens or fillers we meet with difficulties on
account of the secondary radiations (Kays of Sagnac) that are formed
in these screens. As these secondary radiations are less penetrating than
Ihe 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 the 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, be-in £ 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 llayward Pinch, a layer of aluminum
0.2 mm. in thickness completely absorbs these secondary "rays of Sagnac."

CHAPTER VII

THE ABSORPTION OF GAMMA RAYS IN WATER

In this chapter we shall give the results of some of our experimental
work on the absorption of gamma rays.

In these experiments, which were undertaken primarily to determine,
if possible, the absorption of gamma rays in tissues, it was, of course,
impossible to place the ionization chamber used in determining the in-
tensity of the radiations beneath the skin itself.

Water was therefore used in our experiments as being the most suit-
able medium, inasmuch as it is similar in absorbing properties to the
tissues. This medium was previously employed by Kroenig and Friedrich
for determining the absorption of x-rays.

The main problem that we undertook to solve was whether the scat-
tering of the gamma rays causes any change in the intensity of the rays
at various depths below the surface of the skin and if so what the
change is.

So far as the physical side of the problem of absorption and scattering
of radiations is concerned, almost all the previous work mentioned in
the literature has been done by simply interposing thin sheets of absorb-
ing material between the source of radiation and the electroscope. In
some cases an ionization chamber was used. Of such nature, for example,
was the work of Hewlett, who discusses the mass absorption and mass
scattering coefficients of radiations of wave length .13 to 1.05 A° in
various substances including water. He found the mass absorption co-
efficient by finding the ratio of the filtered to the unfiltered beam. The
results indicated excess scattering for the shorter wave lengths.

Kovarik treats of the effect of different types of ionization chambers.
He used an amplification of the current with a three electrode tube.

Christen treats the problem of measuring "intensity" and "dose"
from a theoretic standpoint. Kroenig says that the capacity can be made
low by using a very fine center electrode, but if this is done, the satura-
tion voltage is high.

Kroenig and Friedrich, in their work "Physikalische und Biologische
Grundlagen der Strahlen-therapie," deal extensively with x-ray measure-
ments of this nature. We may, therefore, give some of the details of
their experiments. In his experiments with x-rays Friedrich used an
apparatus of practically the same form as the first type of chamber which
we employed ; the only difference consisted in the fact that in his appa-
ratus the connecting tubes were much larger and were insulated with rubber.
The method that he employed has the great advantage of being flexible

KADI I'M THERAl'Y

hut 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.,

Fig. 4. — Diagram showing electrical connections for null method of using ionization chamber.
El, electrometer or electroscope; R, rheostat; 1C, ionization chamber; E, earth; C, condenser;
'

El,

B, B', batteries.

charges crept out of it as one first used it; this had also been 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 used carbon for the electrodes. Friedrich calibrated
his aluminum chamber with the horn chamber for comparison of different
hardnesses of x-rays.

Makower and Oeiger ("Practical Measurements in Radioactivity")
give a null method of using an ionization chamber. This method consists
in balancing the current to be measured (in the ionization chamber)
with the charge induced on a condenser, arranged in the manner shown.
by varying the voltage applied to the other plate of the latter. (Fig.
4.) The principle of the apparatus consists in keeping the gold leaf

ABSORPTION OF GAMMA KAYS IX \YATKK 51

or mirror as nearly stationary as possible by moving the variable con-
tact on the rheostat, and in measuring the time necessary for a given
amount of motion of the latter.

There appeared to us to be but two methods open for experimentation
if we were to be successful in measuring the gamma ray intensity of
radium beneath the surface of water. By one method it was possible for
us to put the electroscope itself under the water; by the other method
we could use an auxiliary chamber which could be connected in some
manner with the electroscope. The first method involves making a
water-tight electroscope with an insulated and leak-proof connection to
the outside for charging. It also requires that observations be made
through the water with the consequent necessity of bringing the observing
telescope and support near to the point at which the intensity is to be meas-
ured. The latter point seems important although the scattered radiation
must follow the inverse square law; hence the amount of radiation reach-
ing the electroscope would be approximately proportional to the inverse
fourth power of the distance from the source under the conditions assumed.

The second method consists in placing an ionization chamber at the

Fig. 5. — Diagram of first type of ionization clramber. al, aluminum; s-s, sulphur; i-c, inner electrode;

g.t., guard tube.

point at which the intensity is to be measured. The chamber may then
be connected with an electroscope which is thus in an easily accessible
position.

The second method was chosen as being most suitable for our purpose.

A water-tight ionixation chamber, •'! cm. long, 1.56 cm. in interior
diameter, with walls .8 mm. thick was constructed of aluminum (Fig.
5). The inner electrode was made of No. 22 aluminum wire, insulated
from the chamber walls and guard tube with sulphur. The guard tube
running from the chamber had an interior diameter of 6 mm. and was
filled with sulphur. The other end of the chamber was closed with an
aluminum plate. The length of the wire electrode inside the chamber
was about 2.5 cm.

In addition, a water-tight box 55 cm. square and 35 cm. high was con-
structed (Pig 6). The ionization chamber was placed in the center of
the box and about 15 cm. from the bottom, with the guard tube extending
out through one side.

A wooden support for the radium applicator, that was capable of
movement, was constructed so that the shelf for holding the radium to

RADII'M THERAPY

be used could either be brought down to touch the ionizatiou chamber
or could be raised to a height of 25 cm. above it. The shelf could also
be moved 25 cm. to the side in either direction. We thus obtained for
the shelf a freedom of vertical motion amounting to 25 cm.; of sidewise
motion 50 cm. in two directions. Later a string was found sufficient
for changing the position of the radium and was therefore used to sus-
pend the apparatus at different heights.

The level of the water and also the height of the radium applicator
above the surface of the water could thus be varied. The ionizatiou
chamber itself was fixed.

The ioni/ation chamber was first tested. A wire about four meters
long covered with cotton insulation ran from the inner electrode, (con-
necting with the wire passing through the guard tube) to an ordinary
gold leaf electroscope. With this arrangement the speed of leak was
found to be extremely large and also variable. One seventh of a milli-
gram of radium was sufficient to produce a considerable change in the

1C.

Fig. 6. — Diagram of apparatus used for measuring absorption of gamma rays in water. W.E.,
Wilson tilted electroscope; H, ground; B, source of high potential; Sw, Sui*, switches; W, water;
LW , level of water; R.-l, radium applicator; S, adjustable support; I.C., iouization chamber.

leak, but, of course, the actual current in the chamber itself was entirely
too small to be measured.

The use of sulphur supports which were encased in glass for the wire,
did not materially lessen the size and variability of the leak. The wire
was therefore encased in aluminum tubing filled with sulphur.

The first microscope used was of low magnification; 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 without introducing a leak due to the
ionization in the electroscope comparable with the other leaks in the
apparatus. A switch was introduced to separate the ionization chamber
and the tube from the remaining parts of the conductor.

The switch that we vised consisted of a very small glass cup inbedded
in sulphur and filled with mercury, into which the wires dipped.

ABSORPTION OP GAMMA KAYS IN WATER 53

First Observations of Intensities With First Hype of lonization Chamber

Readings were taken with a very high potential 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 reading was almost all leak and that there was little
if any true current.

Readings were extremely irregular. It made a great difference how
high the leaf was charged to start with; the leaf had to be kept charged
for some time before taking readings ; movements 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, however.
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 Wilson tilted electroscope was finally de-

Fig. 7. — Diagram of second type of ionization chamber. S, sulphur; AL, aluminum: A, amber.

vised. The inner chamber was made with approximately the same ex-
ternal dimensions as the previous chamber but heavy aluminum 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 chamber are evident. In 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 possibly occur in this part of the apparatus is from the
inner electrode and the connecting wires 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 may flow
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 potential difference is thus effective in producing
the desired current, but only the low difference is effective in producing
li'iiks.

This second type of chamber is also particularly suited for work with

KADI I'M TIIKUAl'Y

the Wilson tilted electroscope, since the latter measures the rise in
potential above 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 properly adjusted. Instead of the thirty or
forty volt change in potential used with the ordinary electroscope,' a
voltage change of three or four volts or less can he used. Furthermore
it has a low capacity; and the volume of gas contained is small.

Second Series of Observations with First Type of lonization Chamber

An attempt was now made with the old chamber to apply the method
which we proposed to use witli the new chamber; i.e., the outer case

tiiii;:iE; i n

Fig. 8.— Intensity in water. Uasv of applicator 3 cm. above surface.

ABSORPTION OF GAMMA RAYS IN WATER

of the chamber was kept at high 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. However, the following results are at least
qualitative as they indicate the manner in which 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-

net btlw Sun ica // cm. J $

?.— Intensity lie-low Mtrfaic <,! uatir. JSasu of applicator 6 cm. shov

RAblUM THERAl'Y

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 was measured,
and at a constant distance of three centimeters from the surface of the
water. It gives the intensity at various depths below the surface of the
water.

Fig. 9 indicates that 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 was of course less to start with, and the decrease
was more gradual due to the action of the inverse square law. This is
evident from the fact that with a point source the intensity changes

Fig. 10. — Field 5 cm. below surface of water. Base of applicator 1 cm. above water.

ABSOUl'TION OF GAMMA KAYS IN WATER

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
(not 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 goes out from the axis is rather abrupt, as AVC

ii:i im;:

Pig. 11. — Field 10 cm. below surface of water. Base of applicator 1 cm. from water.

RADH'M THERAPY

should expect, since 13- +.52 --= 194, 132 + 102 == 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. 182 + 52 = 349, 182 + 102=424. The ratio between these two
numbers gives a factor of 1.22. (These factors are not actually the
numbers by which the 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 f

Fig. 12. — Field 15 cm. below surface of water. Base of applicator 1 cm. from water.

ABSORPTION OF GAM. MA KAYS IN \VATKK

gradual still. We find that 232 + 5- == 554, 23- r 10- == 62!). The ratio
between these 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 mid the curve in Fig. 12 is extremely marked. The factor
here would be 1.84. (82 + 52 = 89, 82 + 102 = 164.)

The foregoing scries 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.

Fig. 13. — Intensity on surface of water. P.;isc of ap]ilii-atnr 1 cm. from water.

RADIUM THEKAl'Y

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 the applicator.

Slih:

Fig. 14. — Intensity on surface of water. Base of applicator 1 cm. from water.

First Observations of Intensities with the Second Type of lonization

Chambers

We may now discuss the series of curves taken with the second type
of ionization chamber. One of these curves was taken as a calibration
curve for the chamber. The leak across from the inner electrode to

ABSORPTION OF GAMMA RAYS IN WATER

the ground was not small enough to make conditions favorable ; it
changed markedly the values obtained from the reciprocals of the times.
A theoretic deduction of the correction to be applied is as follows:
Let c be the current due to the ionization chamber, i.e., that which is to

Fig. 15. — I'ielil in air. /, parallel to plane of tubes at 3.5 cm. distance. //, perpendicular to plane

of tubes, along axis.

be measured: c'V that due to the leak from the inner electrode to the
ground; V being the voltage to which the leaf has become charged; c"
(V'-V) that from high potential to leaf, V being the high potential.
Then, neglecting a constant capacity factor,

RADIUM THERAI'Y

dV
~dt

— (e+e"F')-(c'+c")F

/»U 0 1 /^ j

f ft rlt

j o (c+c"l")-(c'+c")r Jo1

cs-c'T'
c+c»r_(f'+C">r

1-e -<'•'+''">

'F'

l-e -«•'-""

S — ,

1:::::::

-_L__ j . __,._. ,

::::: ii :::^: ::

IE: ^

_ -5 , .. __

T^^t^

^"i j: — - N . -p.

in air, pi-rjifiidirnlar to plane of tubes.

Al'.SOKI'TION" OF GAMMA RAYS IN WATER 63

TABLE X

INTENSITIES AT VARIOUS DISTANCES ALONG THE LINE PERPENDICULAR TO THE CENTER
OF A 6xfi CM. PLAQUE, WITH 9 TUBES CONTAINING 100 MC. IN ALL

DISTANCES
IN CM.

INTENSITIES (THEORETIC
AT DIFFERENT POINTS ON

VALUES)

THE AXIS

8.5

1.29

9.5

1.0.3

10.5

.866

11.5

.727

12.5

.619

13.5

.533

14.5

.464

15.5

.407

16.5

.360

17.r,

.321

18.5

.288

19.5

.259

20.5

.235

21.5

,214

TABLE XI
INTENSITIES AT VARIOUS 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 S.5 CM. FROM THE PLANE OF THE TUBES

DISTANCES
IN CM.

THEORETIC
VALUES

EXPERIMENTAL VALUES
(CORRECTED BY CALIBRATION CURVE)

1.29

1.28

1.23

1.21

1.17

1.10

1.09

1.04

1.00

.93

.91

.85

.82

.77

.73

.67

.65

.63

.58

.56

.52

.50

.47

.46

.42

.43

.38

.40

.34

.35

.31

.32

The other curves were then corrected by means of the calibration curve
and for air were found to agree very well with the theoretic 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, gradually increasing gradation, then a
point of inflection, and ;i gradual decrease in slope.

RADIUM THERAPY

Curve II is taken along the axis; the slope is at first large and gradually
decreases.

All curves in air can be regarded as combinations of these two types.

Fig. 16 is the original curve for Fig. 15 II. It was by correcting Fig.
16 to the latter that the calibration was obtained.

Second Series of Observations with the Second Type of lonization

Chamber

The apparatus was now set up a second time. Data were taken which
resulted in Fig. 17 for the field in water. The calibration curve obtained

Fig. 17. — Field in water, perpendicular to plane of tubes, o, Experimental values; .r, values cal-
culated on the basis of no absorption; A, values calculated on the basis of fi — .033.

ABSORPTION OF GAMMA RAYS IN WATER

in air was almost identical with that obtained previously ; it is practically
linear, 7 = 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 was
kept at a distance of 3 cm. from the surface of the water, and hence the plane
of the tubes in every ease 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
value 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 between 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-
TANCE

OB-
SERV-

CALCULATED
VALUES.

CALCULATED

FROM

BELOW

PLANE

SUR-

VAL-

S "

AIR.

% DIF-

/t=.033

% DIFF.

M— 05.

% DIFF.

FACE

UES.

NO AB-

FERENCE

OBS 'D.

TUBES.

SORP-

BETWEEN

CAL 'CD.

WATER.

TION.

OBSERV-

ED AND

CALCU-

LATED.

i::.r,(i.-in.

.05cm.

.r,7D

.506

15.55cm.

2. cm.

.408

.388

.363

.351

16.85cm.

3.3 cm.

.325

.334

-3

.299

.285

18.35cm.

4.8 cm.

.257

.284

-10

.242

.223

20.30cm.

6.75cm.

.217

.234

-8

.187

.167

20.65cm.

7.1 cm.

.210

.226

-7

.178

.158

-l.r.Vm.

8.2 cm.

.198

.204

-3

.155

.135

23.15cm.

0.6 cm.

.181

.131

.112

23.95cm.

10.4 cm.

.165

.170

-3

.120

.101

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 were present. This
conclusion was now found, however, to remain true down to a depth of ten
centimeters. In other words, the increase due to the scattering, under

66 RADIUM THERAPY

the conditions used, 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 p = .033, the percentage of difference varies from
approximately 10 per cent from the skin 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 lonization 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 the 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 water and 5 cm. 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 cm. 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 water (with no
change in distance of radium) between the radium and the object radiated
would thus appear to be small.

The 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 relatively large effect due to this change in distance.

Curves I and II thus refer to the same distance of chamber from radium,
and differ only in the amount of water between the two. Curves I and III,
on the contrary, refer to the same distance of surface of water from radium,
and differ only in the depth 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 very well by Curves II and III.
The rate 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 apply the null method mentioned by Makower and Geiger
(previously referred to) it was found that with the condenser at hand the

ABSORPTION OF GAMMA RAYS IN WATER

leak over the surface of the insulation (which 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.

Fig. 18. — Diagram showing change in intensity due to distance as compared with change in in-
tensity due to absorption 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-

68 RADIUM THERAPY

rectly and pouring sulphur over the connections the insulation would he
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 water relative to those in air. This does not, however, seem tp 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 with the type of chamber that we have
been using.

Although under these circumstances both beta and gam ma rays would
take effect, the error due to the gamma rays would probably be so small
as to be practically negligible.

CHAPTER VIII
PHYSICAL AND CHEMICAL 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 which 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 ioni/ation 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 widely different pene-
trating power may be distinguished. The rays most easily absorbed

70 RADIUM THERAPY

are known as the alpha rays, those less easily absorbed are the beta
rays, while those least easily absorbed arc known as the gamma rays.

Alpha rays are absorbed by about .089 mm. of epithelial tissue. They
are therefore of little or no therapeutic importance. The most pene-
trating beta 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 Rutherford they are
completely absorbed by 2 mm. of lead. The hardest beta rays, after
penetrating 1 cm. of epithelial 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 arc 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 intensity 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 power, hard 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

Radium liberates heat spontaneously and continuously. Compounds
of radium maintain themselves at a temperature several degrees higher
than the surrounding atmosphere. In one hour one gram of radium
element spontaneously generates sufficient heat to elevate the tempera-
ture of 136 grams of water one degree centigrade.

"The 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 expelled from the active matter which are absorbed by the
active matter itself and the envelope containing it." (Rutherford.)

The alpha particles produce the greatest heating effect, furnishing 125
calories of the 136 calories produced by one gram of radium in one hour.
The beta rays bear 4.5 and the gamma rays 6.5 of the remaining 11
calories.

PHYSICAL AND CHEMICAL EFFECTS OF RADIUM RAYS 71

4. EMISSION OF LIGHT

All radium compounds are feebly self-luminous in the dark. This
phenomenon is probably due to the presence in preparations containing
radium of impurities which phosphoresce under the constant bombard-
ment of the rays. This luminosity varies under different conditions.
Radium preparations lose a large amount of their luminosity upon ex-
posure to damp air, but regain it again when the salts are dried.

5. PHOSPHORESCENCE AND FLUORESCENCE

Various bodies phosphoresce 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 arc willemite (zinc silicate), kunzite and sparteite,
barium platinocyanide, 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 when 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 sod;i ybixs 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-

Jli RADIUM THERAPY

peutic 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 were 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 ;is
x-rays may be measured by the Saboraud-Xoire 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., when 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 radioactivity.

CHAPTER IX
BIOLOGIC EFFECTS OF RADIUM RAYS

"^fc

EFFECTS OF RADIUM RAYS ON LIVING CELLS

Numerous experiments have demonstrated the effects of radium rays
on living cells of both the vegetable and animal kingdoms. In this and
the succeeding chapter we shall give the results of some purely experi-
mental investigations which have a direct bearing, however, 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.

Pfeiffer 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 were 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
commiinis, 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. With
a concentration of the emanation amounting to 5 me. 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 which may 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
\vlicii allowed to act in sufficient doses outside of the body of the host.
As to the effect on bacteria in 1 1ssues, however, no results have been ob-
tained experimentally that would indicate that bacteria may be actually

74 RADIUM THERAl'Y

destroyed by radium rays '"Without serious injury to the tissues them-
selves. It may be mentioned, however, that Flemming and Krusius ob-
served inhibition of the growth of bovine tubercle bacilli 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 (he writer and
others following the introduction of radium tubes into tuberculous si-
nuses, etc. Certain chronic ulcers discharge less freely after radiation.
These 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 present 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 be irreparably damaged.

2. Effects on Seeds and Plants

Abbe, Matout, Molisch, Fabre and many others have recorded interest-
ing experiments on seeds and plants. Abbe exposed wheat grains to
mixed beta and 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." Matout 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. Molisch exposed the
buds of syringa vulgaris to the beta rays 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 with strong doses,
had its development stopped completely.

Further illustrations of the effect of the rays on various forms of
vegetable life may be found in special 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 lower forms of
animal life (protozoa, etc.) have been made by Bohn, Halberstaedter,
Will cock, Zuelzer and many others. Only a few of these experiments
can be referred to here.

Halberstaedter and his coworkers radiated trypanosomes and observed
particularly the effect both on their subsequent motility and their power
of infecting animals. With the doses used, the motility of the trypan-
osomes was apparently unaffected. The rays cheeked, however, their
power of reproduction so that infection did not, as a rule, occur. From
this it was inferred that the rays acted particularly on the nuclei which
are the elements responsible for the propagation of the trypanosomes.

BIOLOGIC EFFECTS OF RADIUM RAYS 75

Halberstaedter, therefore, inferred that the radiations affected and de-
stroyed the reproductive functions of the organisms before the nutritive
functions were injured.

The effects on the developing forms of some of the lower animals have
been observed by Bohn, 0., G. and P. Hertwig, Thur, and many others.
Bohn investigated the effects on the spermatozoa, ova and larvae of the
sea urchin. Spermatozoa were rendered less active and finally killed.
Ova and larva? developed more slowly and irregularities of development
and form were observed.

Paula Hertwig investigated the effect of radiations on the development
of the ova of ascaris megalocephala, particularly with respect to the
nuclear changes. Development was slower than normal and irregu-
larities of form were noted. The chromatin of the nuclei was especially
affected and even destroyed.

Thur observed the effect 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
larva? 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 radium 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 emphasize the fact that very important modifica-
tions of vital tissues may be brought about either by a selective or by
an inflammatory effect of the rays. We 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 inflammation. Most
of the histologic examinations of irradiated tissues have been made in

76 RADIUM THERAPY

cases in which a more or less intensive inflammatory 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-
flammatory effect.

EFFECTS OF THE RAYS ON THE SKIN

The macroscopic or clinical appearance of the inflammation 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 after 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
was 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
pigs being used. The clinical effects appeared ten days later. These
consisted of erythema followed by ulceration and crusting. The crust
fell off between the fifth and sixth week. The healed irradiated area
then appeared as a depigmented, hairless, smooth and supple scar.

Histologic Findings Eight or Ten Days after the Commencement of

Exposures

In the epidermis, evidences of inflammation were noted. The nuclei
of the epithelial cells showed enlargement or irregularity of outline to-
gether with thickening of the chromatin fibrils and the nucleolus. In-
tercellular edema was present.

Histologic Findings Ten or Fifteen Days after the Commencement of

Exposures

Epidermal dcsquamatioii was noted and there were evidences of a
granular and pigmentary degeneration in the sweat and sebaceous glands
and in the hair follicles. During this same period the corium was the
seat of an intense congestion and of a beginning embryonic transfor-
mation.

BIOLOGIC EFFECTS OF RADIUM RAYS 77

Histologic Findings Thirty or Forty Days after the Commencement of

Exposures

Two phases were noted. (1) "The phase of embryonic regression"
and later (2) "the phase of fibrosis. " During the first phase the epi-
dermis was restored but the hair follicles and glandular structures were
permanently destroyed. The corium had undergone such changes that
its normal structure was apparently lost. There was a temporary rever-
sion to an embryonic type. The connective tissue and the elastic tissue
underwent a transformation, giving place to innumerable branching
connective tissue cells. These had ramifying and anastomosing proc-
esses. The smooth muscle fibers underwent similar changes, being in-
distinguishable from the other embryonic tissue cells. The small blood
vessels showed a tendency to revert to embryonic forms. The endotho-
lium acquired the plasmodial character of the embryonic type. The walls
of the vessels themselves appeared to be made up of fusiform and stel-
late cells continuous both with the extrinsic proliferating connective
tissue cells and with the endothelium itself. In short, the connective
tissue and vascular system of the corium became converted into an
embryonic and angiomatous type of tissue.

In the second phase, fibrous connective tissue redeveloped. There was
a tendency toward the formation of a fibrous scar which differed, how-
ever, both from the normal corium and from the usual postinflammatory
sclerotic tissue. From the former it was distinguished by the regularity
of the superimposed connective tissue fibers and the intervening cells
and by the fact that the fibrous tissue formed lines parallel with each
other and with the surface. From the latter it was distinguished by the
remarkable regularity of the sclerotic tissue and by "the absence of
fibroid perivascular rings and of vascular obliteration." Six or seven
months after the commencement of the exposures, connective tissue fibers
largely replaced the cellular elements but there was the same remarkable
regularity and parallel arrangement of the sclerotic tissue.

In a second series of experiments carried out by Dominici and Barcat

"the same radium plaque screened with 0.5 mm. of silver was used. As
this screen filtered out more than 96 per cent of the hard beta rays, the
gamma rays were responsible for the main changes. After an exposure
of fifty minutes no changes were observed. After an exposure of four-
teen hours, there were found histologically an enlargement of the nuclei

' of the cells of the epidermis and evidences of congestion of the corium.
The latter condition was accompanied by a slight hypertrophy of the
nucleus and cytoplasm of the connective tissue cells. After an exposure
of two or three days there was superficial but temporary destruction of
the epidermis. The corium displayed histologic changes that were not
to be distinguished from those occurring after an exposure of fifty min-
utes to the unscreened apparatus.

78 RADIUM THERAPY

Lazarus-Barlow has carried out a series of experiments to determine
the histologic effects of radium rays on columnar and squamous epithelium.
Two tubes, one containing 92 milligrams and the other 38 milligrams of ra-
dium bromide (about 49 milligrams and 17 milligrams of radium element)
were chosen and allowed to act under the conditions described below for
thirteen and one-half and thirty minutes, respectively. The two tubes, hav-
ing nearly the same screening of platinum and acting under the above con-
ditions ( i.e., a larger quantity for a shorter time and a smaller quantity for
a longer time) produced the same total amount of ionization. From this
standpoint, therefore, the dose was considered as being the same from each
tube. Each tube was inserted into the rectum of a series of rats so that
3 different areas covered by 3 different kinds of epithelium were affected,
viz., the rectum (columnar epithelium), the anus (moist squamous epi-
thelium) and the under surface of the tail (dry squamous epithelium).
The animals were killed so that the effects on the first, second, third,
seventh, eighth and ninth days after exposure could be studied. The
chief effects were the following:

Columnar epithelium region : 92 mg. acting for 13% minutes produced
in general less inflammatory changes than 38 mg. acting for thirty minutes.
This was found to be the case during every period — first to ninth day of the
examination.

Immediately adjacent to the tube, more disturbance of mitosis but less
inflammatory reaction was observed from the effects of the 92 milligram
tube. At a short distance from the tube, less disturbance of mitosis and
less inflammatory action was produced by the 92 milligram tube. De-
generative effects, however, such as desquamation, mucous formation,
mucoid degeneration, and nuclear changes were more marked as a result
of the action of the 92 milligram tube.

In the moist squamous epithelium region the reverse of the above find-
ings was noted. Thirty-eight milligrams acting for thirty minutes pro-
duced more changes in the cells — reduction in number of mitoses, swell-
ing of the nuclei and loss of staining qualities — than 92 milligrams acting
for thirteen and one half minutes. There were no inflammatory changes.

In the dry squamous epithelium region also the 38 milligram tube in
thirty minutes produced more marked alterations in the cells, such as
inhibition of mitosis and loss of staining qualities, than the 92 milligram
tube in thirteen and one-half minutes. The sphincter ani muscle under-
lying the epithelium was also more affected by the 38 milligram tube
acting for thirty minutes.

In another series of experiments, the effect of rays of different char-
acter, obtained by varying the thickness of the screens covering the
tubes, was studied. The 92 milligram tube was used but was covered
with platinum screens varying in thickness from 0.5 mm. to 2 mm. When
a thickness of 0.5 mm. of platinum is used the hard beta rays accompany
the total gamma radiation. When a thickness of 2 mm. of platinum is

BIOLOGIC EFFECTS OF RADIUM RAYS 79

used the hard beta and soft gamma rays are eliminated, only the
hard gamma rays acting. The radium was maintained at the same dis-
tance from the tissues in the different experiments by coating the screens
with paraffine wax so that their outside diameter was uniformly 8 mm.
The time factor of the exposures was varied so that each dose produced
the same total ionization. The difference in the • exposures therefore
consisted only in the different quality of the rays employed. Under
these conditions, the epithelium and subepithelial tissues showed greater
damage as a result of exposures made with the thinner screens (hard beta
plus gamma rays) than with the thicker screens (hard gamma rays).

In still another experiment, the same two tubes containing 92 and 38
ing., respectively, were used. The 92 milligram tube was allowed to
act for one hundred and eight minutes and the 38 milligram for two
hundred and forty minutes. Measured by the total amount of ionization
produced, the dose with each tube was the same. Each tube was in-
serted into the lower end of the rectum of a rat so that both this part
of the rectum and the adjacent parts of the tail were exposed to the
rays. The two animals were killed on the ninth day after the exposure.
The chief effects were the following:

In the columnar epithelial cell region the 38 milligram tube acting for
two hundred forty minutes produced more destructive effects than did
the 92 milligram tube acting for one hundred eight minutes. The mucous
membrane in contact with the tube in some places sloughed away.

In the squamous epithelial cell region the effects were reversed. Here
the 92 milligram tube produced more marked inflammatory changes and
destruction of squamous cells in one hundred eight minutes than did
the 38 milligram tube acting for two hundred forty minutes.

The following inferences may be drawn from these experiments : In-
asmuch as less damage was ordinarily done to the normal columnar epi-
thelium regions when the quantity factor was large and the time factor
small, this general method of procedure may be adopted in making
therapeutic applications to these regions.

In the case of squamous epithelial cell regions, the reverse effects were
noted, i.e., less damage' was done to normal tissues by the smaller quantity
acting for a longer time. In the treatment of these regions therefore
it is probable that a smaller quantity allowed to act for a longer time
may be theoretically used with advantage. It must, be emphasized, how-
ever, that conclusions drawn from these and similar experiments must
not be accepted too literally.

Practical experience has shown conclusively that not less than 50
milligrams of radium element and in some instances more than twenty times
tliis quantity should be used in dealing with malignant conditions. One
must not be misled, therefore, into assuming that very small quantities
of radium are capable of seriously affecting large masses of malignant,
tissue no matter how prolonged may be the exposure. According to

80 RADIUM THERAPY

some authors, too small a quantity of radium may even do serious harm
by stimulating cellular activity.

EFFECTS ON THE SPLEEN, LYMPHATIC GLANDS AND BONE

MARROW

The action of radium rays on the normal spleen, the lymphatic system
and the hone marrow has been investigated by Thies, Heinecke and many
others. Thies irradiated white mice "in toto" with 20 milligrams of
radium bromide for various periods. After a prolonged exposure (nine
to eleven days) he found that the spleen, the lymphatic glands, and
solitary lymph follicles showed an absence of lymphocytes. The spleen
Avas diminished in size and small masses of pigment Avere found through-
out the pulp and especially around the arteries. The supporting con-
nective tissue Avas increased. Heinecke found similar changes in the
spleen as the result of irradiations. This author irradiated the exposed
spleen of rabbits and guinea pigs for as short a period as five seconds
and detected pronounced destruction of the nuclei of the cells. The
same length of exposure produced no change Avhatever in the skin. He
found also that radiation of the abdominal Avail for one hour with twenty
milligrams of radium bromide caused pronounced destruction of the
lymphocytes in the abdominal cavity. Gudzent investigated the effect
on the spleen and other organs of injections of large doses of thorium
X. The results Avere very similar to those produced by external radia-
tions. According to this author, following the injections the entire spleen
exhibits marked hyperemia. Its volume is later diminished. The cells
of the spleen pulp decrease in numbers and in some places disappear al-
together. On the other hand, the capsule and trabeculae are thickened
and appear more prominent. Deposits of pigment are seen throughout
the entire organ.

As to the change in the bone marroAv, Thies found, in the experiments
previously referred to, that in some cases, the marroAv cavity of the bones
was packed Avith erythrocytes Avhile hemorrhages were common. In other
cases, the bone marroAv shoAved almost no cellular elements although an
occasional polymorphonuclear or mononuclear cell was seen.

The favorable effects on the spleen and the blood picture, such as de-
crease in size of the spleen, decrease in leucocytes, etc., noted in cases
of leukemia subsequent to radiations of the spleen, are referred to in a
later chapter. In general it may be inferred from the experiments
mentioned above as well as from a great deal of clinical evidence, that
the spleen, lymp'hatic glands and bone marroAv are extremely sensitive
to radium radiations.

EFFECTS ON THE BLOOD

The blood either "in vivo" or "in vitro" may be affected by the rays.

BIOLOGIC EFFECTS OF RADIUM RAYS 81

Blood "in Vivo"

Only a few of the numerous experiments undertaken to determine the
action of radium on the blood "in vivo" will be mentioned. Bouchard,
Curie and Balthazard found that a marked decrease of the leucocytes
occurred in mice which were made to inhale large quantities of radium
emanation. Von Noorden and Falta found that inhalations of emanation
caused primarily an increase of the leucocytes but later a decrease was
sometimes noted. On the other hand, if a considerable quantity of emana-
tion (100 me. dissolved in 20 c.c. of normal salt solution) is injected
subcutaneously no marked changes will occur in the blood (Price Jones,
cited by Colwell and Russ). Brill and Zehner injected soluble radium
salts subcutaneously into dogs. In one case, .184 mg. and in another case
.064 mg. of radium chloride was used. They found that an increase both
in the number of red cells and of leucocytes resulted. The effect of large
doses was to decrease the number of leucocytes.

In the experiments of Thies, who irradiated white mice "in toto," a
marked diminution in the number of leucocytes in the blood resulted.
The polymorphonuclears were very scanty and the mononuclears were
almost absent.

Aubertin and Delamosse found that radiations of animals produced
a transient leucocytosis followed by a long continued leucopenia.

In a case of myelogenous leukemia, reported by Renon, Degrais and
Thibaut, the splenic area was rayed although the spleen had been pre-
viously removed. Changes in the blood, such as diminution of leu-
cocytes, etc., were produced that were practically identical with those
found when the spleen is present and subjected to radiations. One may
almost certainly conclude that these changes were due to the direct
effects of the rays on the blood itself during its circulation through the
abdominal cavity.

The effect on the blood of the internal administration of radium will be
further considered in the chapter devoted to radium in internal medicine.

From the experiments already mentioned we may draw the following
conclusions as to the effect of the rays on the blood :

Radium may affect the blood whether given internally or allowed to
act externally.

As a result of the internal administration of radium or its derivatives,
either by injections or inhalations, a pronounced effect may be produced
on the blood and especially on the leucocytes. By this method of admin-
istration the whole organism and especially the hemopoietic organs re-
ceive a general though slight bombardment by the rays.

By means of external radiation of the whole body, or of the spleen
especially, similar effects may be produced. The effect, in general,
on the blood, of therapeutic doses acting internally or externally is to
produce a leukopenia, which follows an initial transient leucocvtosis.

82 RADIUM THERAPY

The red blood cells and hemoglobin are frequently increased. While the
exact mechanism of the action of radium on the blood is not thoroughly
understood, it seems probable that the rays may act both directly on the
elements of the circulating blood and also indirectly by affecting the
hemopoietic organs.

Effect on Blood Coagulation

According to von den Velden, small therapeutic doses of radium in-
ternally cause the blood "in vivo" to coagulate more quickly. This
result was noted in a case of hemophilia. The effect is only temporary.
As the result of the administration of large doses of radium, causing a
pronounced leucopenia, Kohom (cited by Gudzent) found that the blood
coagulated more slowly. Von Domarus and Salle observed the same
effects from large doses of thorium X.

Blood "in Vitro"

Blood "in vitro" may also be affected by exposing it to the radiations.
According to Chambers and Russ, the red blood cells may be hemolyzed,
especially by the alpha rays. Citrated blood exposed to radium emana-
tion (.52 me. per c.c.) was almost completely hemolyzed at the end of
forty-eight hours.

According to the same authors, the phagocytic power of the leucocytes
is reduced by exposure to the emanation, while prolonged exposure re-
sults in their complete disintegration. When blood serum is exposed to
alpha rays, the properties of opsonin and hemolytic complement are lost.

Effects of the Rays on the Blood Vessels

The changes in the vessels that may be caused by radium rays have
already been mentioned. Halkin, Thies, Horowitz and many others have
described the changes produced in normal vessels. In general, the endo-
thelium of blood vessels is extremely sensitive to radium rays. The
eiidothelial cells swell up tremendously so that the lumen of the vessel
may be obliterated. Later, degenerative changes take place and the cells
disappear. The tiinics of the vessels become infiltrated with leucocytes.
Capillary hemorrhages may occur and later complete vascular oblitera-
tion may take place.

EFFECT OF THE RAYS ON CONNECTIVE TISSUE, MUSCLE AND

CARTILAGE

Thies found that the white fibrous connective tissue, when exposed to
the rays, underwent destruction. This effect was in direct contrast to
the effect on the yellow elastic fibers which even after prolonged expo-

BIOLOGIC EFFECTS OF RADIUM RAYS 83

sures remained apparently intact. Dominici and Barcat confirmed the
resistance of the yellow elastic fibers to the rays. According to the latter
two authors, elastic fibers reappear in considerable proportion as a post
radiation process. The smoothness and suppleness of the radiation scar
is explained by this fact and also by the absence of excessive connective
tissue formation in the scar.

Striated muscle degenerates under the action of the rays, the muscular
fibers being replaced by connective tissue.

Hyaline cartilage may be initially destroyed but later there may be
observed pronounced hypertrophic changes in the cartilage itself. The
earlier observations of Thies on this point were later confirmed by
Horowitz.

EFFECTS OF THE RAYS ON THE THYROID AND THYMUS

GLANDS

No reports of purely experimental investigations as to the effect of
radium rays on the thyroid and thymus glands have yet appeared. We
may mention here the experiments of Krause and Ziegler and of Rave as
to the effects of x-rays on the thyroid gland of animals. These authors
did not detect either macroscopic 'or microscopic changes in the thyroid
gland due to x-ray radiation. From a clinical point of view, however,
very marked effects on the thyroid gland have followed x-ray exposures
even though the tissue changes were negligible. The clinical effect of
radium on the thyroid was shown first by Abbe and later by Dawson
Turner, Aikens and many others. As a result of radiations with radium,
the thyroid has been noted to decrease in size and functional disturbances
have improved. This topic will be considered again under the discussion
of the treatment of goiter.

The thymus gland in animals has been radiated experimentally with
x-rays by Rudberg, Pigache and Beclere, Regaud et Cremieu and
Eggers. In general it may be stated that atrophy of the organ occurs
as a result of x-ray radiations. The excellent clinical results of Brayton
and Heublein in producing atrophy of the pathologically enlarged thy-
mus in children by means of radium 7-adiations will be referred to in a
later chapter.

EFFECTS OF THE RAYS ON THE STOMACH, LIVER, SALIVARY
GLANDS, PANCREAS AND KIDNEYS

Delbet, Herrenschmidt and Mocquot performed gastrostomy on dogs
and exposed the gastric mucosa to fifty milligrams of radium bromide,
screened with 0.5 mm. of silver, for twenty-four hours. Hard beta and
gamma rays were thus used, the latter preponderating. After a latent
period of eight days, hyperemia and blood extravasation involving the

84 RADIUM THERAPY

mucosa were noted in the irradiated area. Eight to fifteen days after the
exposure marked destructive effects throughout the whole thickness of
the mucosa were found. At the site of application of the radium, the
superficial epithelial cells and the cells of the glands of the mucosa were
destroyed. In the adjacent areas there were evidences of stimulation of
these cells. The connective tissue of the mucosa and submucosa showed
hyperplastic changes. No changes were observed except in a small area
3 cm. in diameter which was the site of the attachment of the radium tube
to the stomach wall.

Thies, Horowitz and Mills have described the changes resulting from
exposure of the liver to radium rays. Thies applied 20 mg. of radium
bromide for six hours to the surgically exposed liver of a guinea pig.
The radium was practically unscreened. Examined at intervals between
the first and fourteenth day, the main histologic changes were early
hyperemia and hemorrhages in the liver lobules, followed later by necro-
sis of the liver cells with separation and compression of the necrotic areas
by newly formed connective tissue.

Horowitz exposed surgically the submaxillary gland and also the pan-
creas of rabbits and inserted 1 mg. of radium bromide unscreened. Local
destruction of glandular tissue, followed by connective tissue repair, was
noted. The same author used 20 mg. of radium bromide for experiments on
the kidneys of rabbits. Inserted into the kidney for ten days, localized areas
of necrosis were produced. Short radiations produced merely marked
hyperemia.

EFFECTS OF THE RAYS ON THE TESTIS AND OVARY

Thies found that exposure of the testis of adult guinea pigs to 20 mg.
of radium bromide for twenty-four hours resulted in destruction of the
seminiferous epithelium. Fourteen days after exposure, no spermatozoa
could be detected. Horowitz has confirmed Thies' experiments. Horo-
witz exposed the ovary of a rabbit to one mg. of radium bromide for ten
days. This resulted in atrophy of the graafian follicles.

EFFECTS OF THE RAYS ON THE NERVOUS SYSTEM

Danysz exposed surgically the brains and spinal cords of mice, guinea
pigs and rabbits and observed the effects of small amounts of radium
(1 mg. radium salt) upon the central nervous system. Symptoms of
paralysis, etc., appeared later and although no histologic changes were
detected in the actual nerve elements, hemorrhages were noted. This
observation led to the somewhat erroneous conclusion that the central
nervous system was very easily affected by radium rays. Later Ober-
steiner, in many experiments on white mice, found marked inflammatory
and degenerative changes in the vessels of the central nervous system.

BIOLOGIC EFFECTS OF RADIUM RAYS 85

He concluded that the symptoms of nerve derangement were fully ac-
counted for by the vascular changes.

Horsley and Finzi experimented on the brains of monkeys. After
trephining the skull, 55 mg. of radium bromide screened with 0.5 mm. of
platinum and 1 mm. of rubber were placed on the brain substance and
allowed to remain for two and one-half hours. The gamma rays were
evidently responsible for the principal effects. No changes in either
the nerve cells or the neuroglia could be made out at the end of twenty-
six and thirty-one days, respectively. Marked vascular changes, how-
ever, such as thromboses and hemorrhages, were found. These authors
also concluded that nerve tissue itself was relatively insensitive and that
the vessel disturbance accounted for any nerve derangements.

As to the peripheral nerves, Okada and Scholtz found no alteration of
the nerve substance after irradiating the sciatic nerves of rabbits. Horo-
witz, however, found in similar experiments, atrophic changes in the
axis cylinders and destruction of the myelin sheath.

EFFECTS OF THE RAYS ON THE EYE

Birch-Hirschfeld studied the effects of 20 mg. of radium bromide when
applied over the closed eyes of rabbits for periods of 4 to 6 hours. The
effects were identical with those due to exposure to x-rays. After a
latent period inflammatory changes appeared consisting of blepharitis,
conjunctivitis, interstitial keratitis, and iritis. After several weeks these
disturbances disappeared. Thirty-nine to 60 days after the exposures,
retinal degeneration or optic atrophy or both effects occurred, differing
according to the conditions of the experiments.

Certain physiologic optical effects may be referred to here. Hardy and
Anderson have confirmed the earlier observations of Giesel and others
as to certain optical effects of the radiations. The sensation of light pro-
duced in a dark room by bringing a radium preparation in front of the
closed eyelid is due to the action of the gamma rays (the closed eyelid
absorbing the beta rays) on the retina. The same effect is produced in
the blind if the retina is intact.

The lens and retina of the eye are markedly phosphorescent upon ex-
posure to both beta and gamma rays. If the phosphorescence of radium
itself is obscured by black paper in a dark room, the open eye may still
detect luminosity due, it is believed, to the phosphorescence produced in
the eye ball.

Certain general conclusions may be deduced from a consideration of
the observed effects of radium rays on vital tissues.

1. A latent period is always present after the application of radium.
This period may last for several days or weeks. Histologk changes can
be detected usually in a few days but clinical changes may be deferred

86 RADIUM THERAPY

for 2 or 3 weeks. After exposure to beta rays (mixed with gamma) the
latent period is shorter and signs of inflammation are more pronounced
than when gamma rays alone are used. The use of considerable quan-
tities of radium shortens the latent period.

2. Radium rays have a "selective" or as some would prefer to call
it a "differential" action on vital cells. Col well and Russ have suggested
the term "selective absorption." The latter term suggests "that the
more the rays are absorbed the greater the action they have." The phys-
ical evidence would indicate that two tissues of the same density will
absorb the same quantity of gamma rays, while the clinical results in the
two types of tissue of the same dose of rays may vary widely, depending
on the sensitiveness of the cell to the rays. All cells may be influenced
and modified and may even be destroyed by the rays if the dose is great
enough.

As we have previously said, vascular endothelium is particularly
sensitive to the rays. In tissues rich in vessels, therefore, there is little
doubt that at least part of the effects observed are due to the action of
the rays on the blood vessels. The sensitiveness of vascular tissue to
radium rays accounts for the excellent results obtained in angiomata.
Sometimes these tumors can be made to retrogress without macroscopic
evidences of inflammation.

EFFECT ON BLOOD-MAKING ORGANS

The hematopoietic organs — spleen, lymphatic glands and bone mar-
row— are the most sensitive of all the tissues to the rays.

An important generalization as to the effect of x-rays has been made by
Bergonie and Tribondeau. There is evidence to indicate that the same
general law holds for radium rays. According to these authors, imma-
ture cells and cells that are actively dividing are more susceptible to
x-rays than adult cells or cells that have already acquired the functional
and anatomical characteristics of complete maturity.

THE METHOD OF ACTION OF RADIUM RAYS ON NORMAL CELLS

Various theories have been advanced to account for the changes in
tissues that have been subjected to radiations. According to G. Schwarz,
the radiations cause in the cells a chemical change, the main feature of
which is the disintegration of lecithin. The lecithin theory, however, has
not been confirmed by other researches. Wohlgemuth, Loewenthal and
others have advanced the theory that the effect on the cell ferments is
the essential factor in causing tissue changes. Later researches indicate
that the radiations do not affect the ferments.

Ricker's theory, formulated as the result of his experimental studies

BIOLOGIC EFFECTS OF RADIUM RAYS 87

on the ear and kidney of the rabbit, is the following: As the result of
the radiations the nerve supply of the blood vessels is first stimulated.
This is followed by vascular dilatation and stasis. The cellular changes
result from these effects. This theory neglects the fundamental studies
of Hertwig which show that the nucleus of the cell is the first point of
attack of the rays.

Another purely hypothetical suggestion, which is not supported by
any experimental evidence, is that the plasmatic colloids of the skin are
changed so that the ions of the surrounding medium enter into the cells
and thus injure or destroy them. Gudzent has summed up our present
knowledge of the nature and cause of the cellular changes produced by
radiations as follows: "We may recognize both histologic and func-
tional primary changes in irradiated cells. Histologically, the nucleus of
the irradiated cell shows a 'foamy or honey-combed swelling.' In some
cases there may be a shrinking and disintegration of the nucleus. The
cytoplasm either shows no change at all or a slight 'foamy swelling'
which may be secondary to the nuclear change. The more actively
mitotic or reproductive the cell is, the more radiosensitive it is found
to be.

"Heinecke called attention to the effect of the rays on certain highly
radiosensitive cells such as lymphocytes and certain cells of the bone
marrow. In these cells there was found to be practically no latent period
after radiation. Within an hour after exposure to the rays, the nuclei
of the lymphocytes showed signs of complete disintegration. This was
shown by the presence of pycnotic globules and nodules which were at-
tacked by phagocytes and in twenty -four hours disappeared almost com-
pletely. The same changes were observed in the cells of lymphosarcoma,
which is also highly radiosensitive.

"One is forced to the conclusion that in these cases, at least, the essen-
tial primary effect of the rays is the direct action on the nucleus of the
cell, causing its destruction. The cytoplasm of the cell is injured, also,
but to a lesser degree.

"Functionally, the change in irradiated cells is shown by various experi-
ments, such as those of Halberstacdter with reference to the effect of the
radiations on trypanosomes and of von Wassermann on mouse carcinoma.
These experiments tend to show that the primary functional change in the
cells consists in the loss of their power of propagation. The nutritive
powers of the cells are affected secondarily.

"We may thus conclude, in a word, that anatomically, the nucleus is the
direct point of attack of the rays on the cell, and functionally, the repro-
ductive power of the cell is the first to suffer. As to the ultimate nature
or the exact character of the changes in the cell, we are still without ade-
quate knowledge." This topic will be referred to again in the discussion
of the changes in irradiated malignant cells.

88 RADIUM THERAPY

EFFECTS OF THE DIFFERENT TYPES OF RAYS
Alpha Rays

The alpha rays, being practically always absorbed by the radium con-
tainer, are never used therapeutically to the exclusion of the beta and
gamma rays. Theoretically they could be employed by using Radium F.
(polonium) as a source of the radiations inasmuch as this substance
emits only alpha rays. According to Gudzent, the effect on the skin of
radiations with polonium are similar to those observed after beta or
gamma rays are allowed to act, i.e., an inflammatory skin reaction is
produced. According to Becton and Russ, certain experiments done first
with all the rays and then subsequently with the combined beta and
gamma rays indicate that certain effects are due only to the alpha rays.
Thus the disappearance of Altmann's granules in cells of healthy tissue
is noted after using all the rays but this does not occur when beta and
gamma rays are used. Gudzent states that by injections of thorium X,
the organism is subjected mainly to an alpha ray effect. This topic will
be considered again in a later chapter.

Beta Rays

In therapeutic applications in which the effect of the beta rays is espe-
cially desired, unscreened radium is applied to the tissues. Beta rays
are always mixed, however, under these conditions, with gamma rays.
Most of the experimental work undertaken to determine the action of the
radiations on tissues has been done with mixed beta and gamma rays,
although unfortunately the exact conditions of the experiments have
not always been stated. As we have already shown in considering the
subject of screens and filtration, varying portions of the beta rays may
be employed depending on the thickness of the screens used.

Abbe deflected the beta rays by means of a strong magnet, and was
thus able to use them alone unmixed with gamma rays. He achieved good
results in various skin diseases. The practical difficulty in this procedure
will probably prevent extensive use of this method, although it is inter-
esting from a scientific standpoint. In the ordinary varnish or glazed
plaques, devised for therapeutic applications, beta rays form about 90 per
cent of the total radiation escaping from the instrument, when no screen
is used. In applications lasting from several minutes to several hours,
therefore, the effect of the beta rays greatly preponderates.

Gamma Rays

After filtering out the beta and some of the softer gamma rays by
2 mm. of lead the hard gamma rays alone act on the tissues. The experi-
mental effects of these have been studied by a few authors and especially

BIOLOGIC EFFECTS OF RADIUM KAYS 89

by Dominici. The problem as to whether all three types of rays — alpha,
beta, and gamma — have an identical effect on the tissues is not entirely
settled. Colwell and Russ state that "different rays give rise to quite
different effects upon one and the same variety of cell." Pappenheim,
Pleseh and Silva Mello, also, from their studies of the results of injections
of thorium X, the effects of which are due largely to alpha rays, believe
there is a difference between these effects and those of the beta and
gamma rays. Heinecke, however, who subjected the entire organism of
animals to x-ray exposures sees a great similarity in the biologic effects
of thorium X and x-rays. In Heinecke 's experiments with x-rays just
as with injections of thorium X, the hematopoietic organs — spleen, lym-
phatic glands and bone marrow — were especially injured. All other
organs were much less affected.

In an attempt to settle the problem of the identity of the biologic
effects of alpha, beta and gamma rays, Oudzent and Levy carried out a
series of comparative histologic examinations. The different organs,
such as the spleen, bone marrow, lymph glands, liver and kidney of rats
were sectioned, the animals having been killed by injections of thorium
X, by roentgen rays, and by radium radiations, respectively. They con-
cluded that the histologic effects of alpha, beta, and gamma rays were
the same.

In contradistinction to some of the authors mentioned above, Gudzent,
therefore, feels justified in assuming that the effect of the different rays
depends solely upon the sensitiveness of the cells. The idea of an elec-
tive action of the different rays, by which each type of ray acts differ-
ently on the same cell, is thus not borne out. This author comes to the
conclusion that the same explanation of the biologic effects of the rays
may be given as for its physical and chemical effects. The radiated body,
through ionization, becomes practically an electric field, which comprises
the positively and negatively charged parts of the radiated material. In
this ionization of the radiated tissues lies the explanation of the biologic
effect of the rays.

From the clinical point of view it would appear to the writer that the
same cells may react differently to different types of rays, in accordance
with the belief of Colwell and Russ. Thus the angiomata, as a class, are
very sensitive to both the beta and gamma rays from radium, sometimes
yielding to doses that produce no visible inflammation. On the other
hand, angiomata are not at all sensitive to x-rays yielding only to destruc-
tive doses with the latter agent.

Other examples, illustrating the different effects of different rays upon
the same type of cell, might be cited but the full elucidation of this
topic must await further investigations.

CHAPTER X
BIOLOGIC EFFECTS OF RADIUM RAYS (CONTINUED)

EFFECTS OF RADIUM RAYS ON MALIGNANT CELLS

Effects of the rays on rat and mice tumors. Certain tumors of rats and
mice, it is \vell known, can ordinarily be transplanted from one animal
to another by subcutaneous inoculation. These tumors afford, therefore,
good material for experimental observations. The effects of the rays on
these growths have been investigated by Apolant, Bashford, Murray and
Cramer, Chambers and Russ, von Wassermann, Wedd and Russ, Wood
and Prime and many others. It is possible to refer here to only a few of
these experiments.

Apolant, who was one of the earliest investigators, found that radium
applied to certain types of mice carcinoma "in vivo," i.e., in the body of
the animal, caused the tumor to disappear in most cases and to diminish
in size in others. As the result of histologic investigations, Apolant
attributed the destruction of the tumor to the direct action of the rays
on the cells. The connective tissue proliferation noted in the tumor was
regarded as a secondary process.

Bashford, Murray and Cramer, in their experiments with Jensens
mouse tumor, observed disappearance of the growths after radiations
but did not detect any microscopic changes in the tumor cells. The
marked connective tissue proliferation and frequent hemorrhages, noted
by these authors, were regarded as the primary changes and the disap-
pearance of the tumor cells was believed to be a secondary process.

Wedd and Russ and Chambers and Russ showed that portions of mice
tumors if excised and exposed "in vitro," i.e., outside the body of the
animal, to a sufficient dose of radium rays could no longer be inoculated
successfully into other animals. Smaller doses checked but did not pre-
vent the growth of the inoculated tumor. They concluded therefore, that
the change or changes set up in the tumor cells themselves were respon-
sible for the failure of the inoculated tumors to grow. The beta rays
seemed to have a more powerful inhibitory effect on the tumor growth
than the gamma rays.

Von Wassermann irradiated small pieces of mouse cancer "in vitro."
In certain experiments the tumor retained its vitality when inoculated
but did not develop. From this he concluded that while the rays acted
directly on the tumor cells, they did not actually kill the cells but rather
impaired their proliferating power. In other words, the rays acted chiefly
on the propagating function and to a less extent on the nutritive function
of the cell. This observation gave rise to the hypothesis that the actual

BIOLOGIC EFFECTS OF RADIUM RAYS 91

death of the cancer cells was brought about either by the natural aging
of the cells or by the cytolytic powers of the organism itself. This view
has not been generally accepted, however, most observers believing that
the action of the rays on the tumor cell itself and especially on its nucleus
is responsible for its death. This topic will be referred to again in a sub-
sequent section when dealing with the question of immunity.

Wood and Prime have carried out a series of experiments to determine
the action of the rays on certain rat and mice tumors. These authors
have stated quite exactly the experimental conditions under which they
worked with reference to (a) the amount of radium element used and
the kind of container, (b) the screens, (c) the distance of the radium
from the tissues, and (d) the length of exposures.

Tumor cells were exposed both outside and within the bodies of the
animals to the action of the rays. Different types of tumors were used
in the experiments. These included the Flexner-Jobling rat carcinoma,
mouse carcinomata No. 11 and No. 180 of the Crocker Fund series and
the Ehrlich spindle cell mouse sarcoma.

In one series of experiments, tumor tissue was excised and exposed
outside the body of the animal to the radiations from capillary glass
tubes containing 100, 83 and 17 mg. of radium element, respectively. As
only the thin glass wall of the radium tube intervened between the
radium and the tissue, practically all of the beta rays in addition to the
gamma rays were effective. As proved by subsequent inoculation, the
time required to kill the tumor cells was 10 minutes for both 100 and
for 83 mg., and 20 minutes for 17 mg. The great destructive power of
the softer beta rays was thus well illustrated.

In another series of experiments the tumor cells were also exposed
outside of the body of the animal. The quantity of radium element
contained in the glass tubes in the different experiments was 100, 83, 30,
20, 17 and 10 mg. respectively. The screening was 0.4 mm. of brass
plus 0.65 mm. of glass. As this screening absorbed the alpha and softer
beta rays, the hard beta mixed with gamma rays were effective. The
distance was 1.05 mm. (0.4 + 0.65). The time required for a lethal dose
for tumor cells under these conditions was 45 minutes with 100 mg., 60
minutes with 83 mg., 90 minutes with 30 mg., 150 minutes with 20 mg.,
180 minutes with 17 mg., and 300 minutes with 10 mg.

In still another series of experiments the conditions were the same as
in the last experiment but in order to filter out the beta rays and employ
as far as possible pure gamma rays the screening was increased to 1.2
mm. of brass. In addition 5 mm. of filter paper were used between
the tube and the tissues. This additional screening increased the dis-
tance of the radium from the tissues to 6.9 mm. Under these conditions,
100 mg. destroyed the tumor cells in 7 hours, 83 mg. in the same length
of time, 30 mg. in 15 to 18 hours, 17 mg. in 20 hours and 10 mg. in 36

9'2 RADIUM THERAPY

hours. In this last experiment it is seen that the time required for beta
rays to kill tumor cells was approximately 6 to 8 times as long as that
required for beta rays when mixed with gamma rays as described in the
previous experiment. From this observation the authors concluded that
there was a lack of sharpness in the lethal action of the gamma rays as
compared with beta rays. It may be noted, however, that the distance
of the radium from the tissues was about 6 times as great when gamma
rays were used alone as when beta rays mixed with gamma rays Avere
employed.

In still another series of experiments the authors used 83 mg. screened
with 0.4 mm. brass, employing hard beta and gamma rays for 2 hours
over a tumor "in vivo." Exposures longer than 2 hours were not given
on account of the difficulty of further prolongation of the anesthetic.
Upon subsequent inoculation into other animals, some slowing of growth
was noted as compared with the controls, but the irradiated cells, even
directly under the tube, were not killed. This failure was attributed
to the fact that "in vivo," there was a supply of fresh nutriment to the
cells. In addition any chemical products formed by the radium in the
tissues were probably promptly removed. Tissue directly under the
radium tube, but 1.1 cm. away from it, grew, when inoculated into other
animals, as well or perhaps better than the controls. As the beta rays
are absorbed by \ cm. of tissue, this experiment apparently showed that
the gamma rays from 83 mg. could not destroy cells "in vivo" in 2 hours,
although "in vitro" such cells were destroyed in 1 hour.

The following are among the conclusions of the authors.

1. The hard beta rays, mixed with gamma rays, have about 8 times
the lethal effect of the pure gamma rays on malignant cells. Inasmuch,
however, as the beta rays are absorbed by 1 cm. of tissue, the gamma rays
must be used for deep effects.

2. Sublethal exposures S!OAV the growth of tumor cells for a certain
length of time while still shorter treatments seem to stimulate the cellular
activities.

3. The dose of radium rays required to destroy tumor cells "in vivo"
is greater than that necessary to destroy isolated cellular elements.

This observation explains the fact that an exposure capable of destroy-
ing a small metastatic carcinoma nodule in man is quite ineffective in
the case of a well-vascularized primary carcinoma.

EFFECT OF THE RAYS ON HUMAN CARCINOMA

The clinical part of our work deals fully with this topic. It will be
of interest, however, to mention here a few experiments which have
been made to determine the dose of radium rays necessary to destroy
human carcinoma.

F. C. Wood has made some investigations with reference to the effect

niOLOGIC EFFECTS OF RADIUM RAYS 93

of the gamma rays on metastatic skin nodules in cancer of the female
breast. He found that exposures of 6 to 8 hours with 83 to 100 mg. of
radium element, screened with 1.2 mm. of brass and 5 mm. of filter paper,
caused, in many instances, permanent disappearance of the nodules.
Shorter applications showed the rate of growth of the tumor cells but
did not kill them. Still shorter exposures or smaller quantities of radium
had a stimulating effect on the cells. Dr. Henry Schmitz has also carried
out a series of experiments to determine the effect of gamma rays in
connection with recurrent breast cancers in the human body. He applied
to carcinomatous nodules 50 mg. radium element, screened with 1.2 mm.
of brass and placed at a distance of 1 cm. for periods varying from 4 to
13 or more hours. The distance of the nodules from the skin surface
was carefully noted. After 10 days, various nodul.es were removed for
microscopic examination. He concluded that carcinoma tissue within
a distance of 1 cm. was destroyed by the gamma rays from 50 mg. of
radium element after an application of about 12 hours, i.e., 600 milligram
hours. The experiments of Kroenig and Friedrich, referred to in a sub-
sequent chapter in which breast carcinoma was found to be about 1.15
times more susceptible to x-rays than the middle epidermal layer, are
also of great interest.

Histologic Changes in Irradiated Malignant Tumors

We may now direct attention to the histologic changes that have been
observed in irradiated malignant tumors. We shall mention also some of
the various interpretations of these changes.

Extensive histologic observations have been made by Aschoff, Kronig
and Gauss, Barcat, Bumm, Degrais and Bellot, Dominici, Ewing, Faure-
Beaulieu, Morson, Rubens-Duval, Schmitz, Wickham and Degrais and
many others.

According to von Hansemann and Schottlaender, nothing is to be seen
liisfnlogically in irradiated tumor tissue that might not also be observed
in rapidly growing and disintegrating nonirradiated tumors. Ewing,
on the other hand, states that "the series of morphologic changes which
take place after successful radium application is specific and that when
these changes are present in undisturbed course it is possible to recognize
tumor tissue treated by radium."

According to Dominici and Rubens-Duval, radium rays act upon car-
fiiioma cells in two different ways. By one method, the cells are killed
<>iitri«.'li1, without any histologic change occurring that can be detected.
By another method, definite histologic changes occur and can be ob-
served prior to the death of the cell. These changes consist of nuclear
hypertrophy and budding; hypertrophy of the cell body; an increase in
the number and size of the so-called "pseudoparasitic" bodies. In the
case of squamous-cell carcinoma, as of the lip, keratinization may ac-
company the above changes.

94 RADIUM THERAPY

These authors believe that while some of the cancer cells are destroyed
by the rays, others simply have their powers of proliferation arrested.
Other authors subsequently expressed the same belief.

Bumm has reported a case of inoperable carcinoma of the uterus in
which surgical operation was performed after intense radiation of the
tumor. During the operation, carcinomatous nodules were observed
outside of the operation field. Fifteen months afterward, however, the
patient was in good health. Bumm suggested that these outlying cancel-
cells were damaged so that they could not proliferate although histo-
logically the damage could not be detected. Subsequently, in a study of
the morphologic appearance of cancer clinically cured by radium and
x-rays, Levin and Joseph cited several cases in which clinical arrest of
malignancy was apparently brought about by radium radiations, al-
though no morphologic change in the tumor cells could be detected.
These authors also suggested that the first effect of the rays probably was
to inhibit the proliferating power of the cells. Cell degeneration and
death thus occurred, not as the direct result of the action of the rays, but
in the natural course of the life cycle of the cancer cell.

The view that radiation may, so to speak, have a sterilizing effect on
the cancer cells and inhibit their proliferating power without directly
killing them receives some support from the investigations of von Was-
sermann on mouse cancer. These experiments have already been re-
ferred to.

Ewing has given the following description of the histologic changes
occurring in irradiated epidermoid carcinoma of the cervix. "Within
from three to five days after the application in the cervical canal of
300 me. of radium emanation in a platinum tube, there is hyperemia of
the tissues, beginning exudation of the lymphocytes and polymorpho-
nuclear leucocytes and swelling of all the cells.

"In the second week, the cords of tumor cells present a characteristic
appearance. The nuclei are swollen, homogeneous and hyperchromatic.
The cell bodies are enlarged, the cells loosened, hydropic vacuoles appear
in the cytoplasm and fusion giant cells form.

"In the third week, the number of cells is greatly reduced. Many ap-
pear to suffer liquefaction necrosis. Others are invaded and mechani-
cally broken up or compressed by lymphocytes and proliferating stroma.

"From the fourth to the fifth weeks only pycnotic nuclear fragments or
an occasional giant cell are visible or no traces whatever remain. Mean-
time the stroma has been active and appears to take an active part in
the process. Leucocytes become overabundant, the capillaries proliferate
actively and the stroma is transformed into granulation tissue in which
numerous new capillaries penetrate and excavate the tumor cell nests.
The gathering of leucocytes, lymphocytes, plasma cells and polyblasts
in the later stages of radium reaction may be extremely profuse and in
this respect the reaction is somewhat specific.

BIOLOGIC EFFECTS OF RADIUM R.WS 95

"Eventually the site of the tumor is occupied by granulation tissue from
which slight sprfuis and cellular exudate is discharged. Later epithelium
grows over the denuded surface, completing the repair.

"All manner of variations occur in the reaction of tumor tissue to
radium. Complete simple necrosis follows over action of radium. Bulky
tumors may present large areas of simple necrosis in which cysts form by
liquefaction. The stroma as well as the tumor may be destroyed in which
event extensive scarring will result. In the foregoing scheme of changes
it would appear that just enough radium had been employed to cause
slow degeneration of tumor cells and stimulate regenerative growth of
granulation tissue."

Morson imbedded radium, contained in a platinum tube, in the sub-
stance of carcinomata, allowing the tube to remain for periods of from 15
to 24 hours. The thickness of the wall of the tube was such that only
the gamma rays were effective. Sections of the irradiated growths were
examined at various intervals after the exposure. In some cases, his-
tologic changes, consisting of nuclear irregularity and fragmentation,
could be detected in the cancer cells, especially in those adjacent to the
tube, as early as 15 hours after the commencement of the exposure. In
certain cases, 48 hours from the commencement of the exposure, sections
showed cancer cells in different stages of degeneration lying in a disor-
ganized mass of tissue. In many cases, 14 days after the exposure, there
were no evidences of carcinoma cells. In other cases, however, carcinoma
cells could still be detected at the end of 2 months. These cells, never-
theless, showed degenerative changes, such as enlarged nuclear and
vacuolated cytoplasm, while they were encircled by dense connective
tissue.

Gudzent says: "In the histologic changes due to the radiations, we
must place in the foreground the injury and destruction of the nucleus
of the carcinoma-cells. According to the investigations of Grasnick on
embryonal tissue, we must assume that in the nuclei which are under-
going mitotic changes the effect takes place immediately after the radia-
tion and without any latency. These injuries are not disclosed however
until a latent period of several days has elapsed. In the completed
stage, all signs of the disintegration of the nuclei can be observed, such
as decrease of the staining power, swelling with vacuol-formation. and
shrinking and dissolution. The injury to the nuclei undoubtedly causes
the death of the cells. To what extent the cell plasma is injured, is not
as yet known, but one can observe that the cells decrease in numbers
and finally disappear. In addition to these primary changes, others mani-
fest themselves which are of far-reaching importance in the curative
process. Very soon after the first injury to the nucleus and the cell
makes its appearance, extensive proliferation of the connective tissue
sets in. One observes the young connective tissue permeating the swell-

96 RADIUM THERAPY

ing in all directions. This connective tissue breaks open the cell com-
plexes of the parenchyma, encircles single complexes, pressing them to-
gether and strangling them. Sometimes cells with several nuclei are
formed. Klein and Duerk have called these 'conglutinal giant cells.'
These exhibit a lessened power of growth and diminished vitality. One
is led to infer that the connective tissue is actively combating the car-
cinoma cell, limiting and even destroying its vital processes. In a later
stage, the connective tissue shows signs of maturity ; the number of
cells is diminished, while the connective tissue fibers coalesce and become
sclerotic. The cause of the new formation of connective tissue may be
found in the effect of the radiation. We must assume, then, that the
same amount of radiation which causes the disintegration of the cells,
has a stimulating effect on the connective tissue cells. This assumption
is very hard to bring into harmony with the researches of Root. This
author found the fixed connective tissue cells very radiosensitive. To
regard the new formation of connective tissue as a reaction which serves
as an intermediate substance for interstitial spaces cannot be accepted
for the reason that it proliferates very early and in its later stages
especially shows various signs of the influence of the radiation. In all
probability both assumed causes play some part in this, but this must be
cleared up through future research.

"In connection with this connective tissue proliferation, the injury
and destruction of the blood capillaries, whose radiosensibility is well
known, must be considered. Thus the hemorrhages occurring soon after
radiation are explained. It seems to be clear that the interruption of
the blood supply causes severe injury to the carcinoma cells. In the
later stages, proliferation and new formation of capillaries set in. These
accompany especially the newly formed connective tissue bundles. Between
the cell bundles of the parenchyma and those of the supporting tissue, cells
of hematogenous origin, leucocytes, lymphocytes and so-called leuco-
cytoides, can be observed, at a certain stage. According to Klein and
Duerk, the fragmentary nucleated leucocytes especially seem to have
the important role of removing the cell particles which have been de-
stroyed. It can be seen that these cells, like phagocytes, cling to the
protoplasmic bodies which are more or less isolated from their epithelial
cell complexes, and practically gnaw off fragments here and there, so
that a concave shaped loss of substance can be noticed. Sometimes single
epithelial cells are densely covered by these phagocytes, which undoubt-
edly are hard at work causing their reduction and dissolution. This
phagocytic process is to be regarded as secondary and provoked by the
dissolution of the radiated cells.

"If the destruction of all carcinomatous cells has been attained, the
connective tissue completely fills up the interstitial spaces. In due
time it matures, becoming poor in cells and more sclerotic than the con-

BIOLOGIC EFFECTS OF RADIUM RAYS 97

nective tissue which fills up interstitial spaces caused by other con-
ditions."

Dominici has given the following description of the histologic changes
occurring after radium treatment in a very vascular myeloid sarcoma.
From the commencement of the treatment to the complete disappearance
of the growth there elapsed a period of a little over 4 months. It is
noteworthy that Dominici inferred from his studies that not merely were
the malignant cells destroyed by the action of the rays and replaced by
fibrous tissue, but a peculiar evolutionary process was set up in the sar-
coma cells themselves, so that they became, at least in part, converted
into cells indistinguishable from normal connective tissue. The nuclei
of the sarcoma cells became more spindle shaped. Atrophic changes
could also be made out. The protoplasm of the giant and sarcoma cells
became replaced by connective tissue fibers which Dominici believed
arose from the alteration of the protoplasm itself. Adjacent to the
nuclei, however, a portion of the protoplasm remained intact. This
unaltered protoplasm formed, with the nuclei, typical connective tissue
cells. The processes just described occurred throughout the growth.
The lumen of the blood vessels became smaller so that they appeared
like capillaries lying in the midst of fibrous tissue. It seemed that the
malignant sarcoma cells were transformed into fibrous cells. The
fibroma-like structure remained stationary or became smaller, showing
no tendency to increase as in ordinary fibromata. The arrangement of
the connective tissue fibers was remarkably regular.

THE METHOD OF ACTION OF RADIUM RAYS ON MALIGNANT

CELLS

While there has been much speculation as to the mechanism of the
action of radium rays on malignant cells, little is definitely known. The
changes to be observed histologically do not differ from those already
described as occurring in normal cells. The same theories of the action
of the rays which have been referred to in the previous chapter have
also been advanced to explain the morphologic and functional change in
malignant cells. As yet, however, no explanation has been made that
is entirely satisfying and indeed none is likely to be made until our
knowledge of intracellular metabolism is complete.

According to Ewing "it is a reasonable assumption that the gamma
rays while traversing the tissues give rise to secondary beta rays, elec-
trons, which act on the cells. That the action is electrical, accelerating
cell ferments, ionizing gases, altering lipoid emulsions, etc., may be
conceived but is not demonstrated. These questions may well serve to
stimulate and aid in the study of the physics, chemistry, and finer mor-
phology of the cell.

!)8 RADIUM THERAPY

"Interpreted from the pathologic standpoint, the observed changes in
cell morphology indicate an action directly on the tumor cell and es-
pecially on its nuclear mechanism, with profound and progressive chem-
ical changes in the nuclear proteins, attended by the formation of acid
products and by the absorption of material, probably water. The ap-
pearance of the cell cytoplasm suggests hydrolytic cleavage of cell pro-
teins and these seem to excite leucocytic emigration.

"The growth of capillaries may be explained as a regenerative process
following a loss of tissue equilibrium, or it may involve a direct stimu-
lating action of the radium on endothelium and fibroblasts. In any event
the process is very complex and in many cases there are strong hints
;:t a restoration of normal resistance of the connective tissue against
lawlessly proliferating tumor cells."

Summing up the various findings and interpretations, the available
evidence merely suggests the probability that some kind of an intra-
csllular and especially an intranuclear chemical change is produced by
the action of radium rays on malignant cells. The exact nature of this
change still remains a secret. The nucleus of the cell is injured first
and this injury is attended by the loss of the power of mitosis. As a
rule malignant cells are much more susceptible to irradiations than the
cells of most normal tissues. This peculiar sensitiveness forms the
foundation of radium therapy in malignancy.

THE QUESTION OF STIMULATION OF TUMOR GROWTH BY
INSUFFICIENT RADIATION

According to some authors, radiations that fail to kill the tumor cells
may even stimulate their activity and cause increased tumor growth.
This is a problem of the greatest importance and one about which there
is much difference of opinion. Wood and Prime thought that certain
mouse tumors treated with radium and then inoculated into other animals
grew more rapidly than the controls. Ewing remarks, however, that
"their results were quite inconstant, and the extirpation of the exposed
cells removed them from the attack of lymphocytes and granulation
tissue, which are the main agents of tumor destruction set to work in
the curative process excited by radium."

Reference may also be made to the experiments of Hastings, Mac-
Cormac and Woodman. These authors exposed cancerous skin nodules,
secondary to mammary carcinoma, to the radiations from pitchblende.
This mineral contains several radioactive bodies, but the radiations
from a given quantity are at least a million times weaker than those
from the same quantity of radium. One might infer, therefore, that
malignant cells would probably be stimulated by exposure to pitchblende
rays on the assumption of inadequate dosage. The treated carcinomatous
skin nodules, however, showed no recognizable clinical differences from

BIOLOGIC EFFECTS OF RADIUM RAYS 99

the untreated nodules after the lapse of several months. Histologically
the treated nodules disclosed evidences of the effect of even these weak
radiations. Nuclear changes in the cancer cells occurred, the principal
change observed consisting of the partial disappearance of chromatin
which was at the same time condensed about the nuclear membrane.
In addition, delicate connective tissue fibrils appeared between the cancer
cells so that they became separated into small aggregations.

We may refer also to the studies of A. and 0. Hertwig. These authors
have shown that mitosis of cells is inhibited by radiations of even the
weakest intensity.

From the clinical side, many observers, including the writer, have
not been able to convince themselves of an actual stimulation of tumor
growth by radium rays. One may doubt if such stimulation occurs under
the modern method of very large primary doses. If it could be shown
conclusively to occur it would constitute one of the many limitations
of radium treatment to be guarded against as far as possible by power-
ful radiations directed especially toward the periphery of tumors. One
should not forget, however, that very massive treatments with heavily
screened radium may even defeat their own object by causing such
extensive injury to normal tissues as to result in serious harm to the
patient. This fact tends to limit the usefulness of radium in the treat-
ment of very extensive and deeply situated cancerous masses.

The Problem of Immunity

It would be beyond the scope of this work to consider in detail
the complex problem of immunity to malignant tumors. Tyzzer has
recently published a resume of the subject and the reader may be
referred to his monograph. Additional references will also be found
in the bibliography. A few experiments that bear on the production
of immunity by radiations with radium may be referred to. Contamin
was apparently the first to show that if cancer cells were irradiated
for a short time with radium or x-rays and were subsequently
inoculated into mice a degree of immunity was produced. He also ob-
served that an excessive exposure to x-rays destroyed the immunity
conferring power of the cells. Wedd, Morson and Russ confirmed the
general trend of these observations. These authors irradiated "in vitro"
tissues from the Twort tumor (adenocarcinoma) with a measured dose
of beta rays. The radiation was sufficient to prevent the formation of
growing tumors when the radiated tissue was reinoculated into mice
although the tissue, after persisting for several days, was absorbed.
Some days later the animals were inoculated with the usual strain of
tumor tissue which had not been irradiated. As the second graft of
tissue did not develop, an immune condition of the animal was inferred.
By gradually increasing the length of exposure, it was found that a

100 RADIUM THERAPY

point was reached at which the irradiated tissue when inoculated no
longer conferred immunity. Those authors also found that if normal
and radiated tumor cells were inoculated simultaneously no immunity
was produced. In commenting on these experiments, Colwell and Russ,
while recognizing that no generalization can he made on account of the
limited number of the experiments, state that "excessive irradiation of
a tumor may therefore very easily abolish any immunity that the ab-
sorption of irradiated cells may be capable of giving rise to. It would
appear that the best condition for producing immunity is for the cells
to receive an exposure that will insure their gradual degeneration and
disappearance."

It has been asserted by some clinicians that the irradiation of a tumor
such as a breast cancer may cause not only the irradiated tumor but
also distant metastases such as axillary nodules to shrink.

In order to explain this alleged effect, the hypothesis has been ad-
vanced that substances are set free from the irradiated growth which
act on the secondary deposits of the tumor. Rohdenburg and Bullock
have shown however that an established transplanted tumor, i.e., one
that has excited a stroma reaction and obtained a blood supply, is not
susceptible, even though radiumized, to immunity reactions. They have
pointed out that it is much less likely, therefore, that an unradiumized
tumor is in any way sensitive to the immunity process. It is probable,
therefore, as these authors state, that the disappearance of tumors — if
they really do disappear — situated at a distance from the radiated growth
is due to some other process than the influence of substances set free by
radiation. If the shrinkage of such tumors really occurs, it may be due
to the disappearance of inflammatory edema in the nodules and the
destruction of lymphoid elements which are very sensitive to radiation.

The writer would take sides with those who doubt the probability of
any effect of radiation on tumor deposits outside of the field of radiation.
So far as our observation goes, radiumization of a tumor has no effect
whatever on metastatic deposits in other parts of the body.

Rohdenburg and Bullock have also pointed out that the problem of
immunization and cure of animal tumors on the one hand and of human
tumors on the other is a very different one and that the results so far
achieved in developing immunity in animals cannot be transferred to
man.

In man, the problem is to cure or produce immunity against a spon-
taneous tumor.

In animals, immunity has only been produced against transplanted
tumors. According to these authors, an animal cannot be immunized
against its own tumor.

The following observations of Murphy and Norton bear on the problem
of the nature of the immunity process. While the experiments of these

BIOLOGIC EFFECTS OF RADIUM RAYS 101

authors have evoked great interest, it must be said that they have not
been completely confirmed. Sittenfield's experiments, e.g., do not sup-
port their conclusions as to the importance of the lymphocyte in the
defensive mechanism of the organism.

Murphy and Norton, in their investigations of the effect of x-rays on
the resistance to cancer in mice, have apparently shown that the resistance
to heteroplastic tissue depends on the activity of the lymphocytes. The
chick embryo normally lacks the ability to destroy a heteroplastic tissue
graft. If a small amount of lymphoid tissue from an adult is supplied,
it becomes as resistant as the adult. On the other hand, if an adult
animal has the main part of its lymphoid system destroyed by repeated
x-ray radiations, it loses the power of destroying a graft of heteroplastic
tissue. Histologically, the main characteristic of a failing heteroplastic
graft is a marked local accumulation of lymphocytes. The same his-
tologic picture is seen in a failing cancer graft in an immune animal of
the same species. Simultaneously with the production of the cancer im-
munity and while the lymphocytes are accumulating around the cancer
graft, a lymphocytic crisis occurs in the circulating blood. This crisis is
lacking in animals susceptible to the cancer graft. It has been noted
that while repeated small doses of x-rays will destroy the lymphoid ele-
ments of an animal, one small dose will stimulate it and cause a lympho-
cytosis. Bearing in mind these facts, which had previously been demon-
strated, the authors studied the relation of the resistance of mice to their
own spontaneous tumors. Among their experiments, all of which were
carried out with suitable controls, were the following: The cancer was
removed by operation from the animal. The animal was then given a
stimulating dose of x-rays. Immediately afterward, a graft of the
original tumor was placed in the groin of the animal. In a series of 52
animals so treated, 50 per cent were rendered immune to their own
cancer and in the other 50 per cent the return of the disease at the opera-
tion site was greatly retarded. The authors suggest that if one dose of
x-rays causes this effect, a more pronounced effect might be caused by a
second stimulating dose at a subsequent time.

The foregoing experiments have a special interest in connection with
the frequent clinical observation that malignant tumors in humans re-
spond differently to radiation, -some being easily affected while others,
of apparently the same type, are much more resistant. It may be pos-
sible that the different response of similar tumors to radiations depends
to some extent upon the systemic defensive powers of the organism. It
would appear from these experiments that while the radiosensibility
of the tumor cells is probably the chief factor, the lymphocytic system
is also of some importance in connection with the disappearance of
malignant growths under the influence of the radiations. An important
practical lesson may be drawn from these experiments. In cases de-

102 RADIUM THERAPY

manding powerful radiations, frequent observations of the leucocytes
should be made. A marked reduction in the number of leucocytes is a
signal for caution in proceeding with further treatments until the leu-
cocyte count is improved. When the spleen, lymphatic glands and bone
marrow, which are especially radiosensitive, are likely to receive heavy
doses either intentionally or incidentally in the course of the treatment,
it is particularly necessary to proceed with care.

CHAPTER XI

THE RADIUM REACTION

Broadly speaking, all of the biologic effects of radioactive substances
when applied externally or introduced into the organism are due to the
radiations and are manifested by various disturbances which may be
termed reactions.

In this chapter we shall consider only the biologic effect, i.e., the re-
action due either to (1) surface radiations or to (2) the introduction of
radioactive material into tumors. The effects of radioactive material
administered by mouth or introduced intravenously or subcutaneously
will be discussed in the chapter on radium in internal medicine.

1. SURFACE RADIATIONS

These are radiations that are used on the surface of the skin. They
may produce (a) a constitutional reaction or (b) a local reaction.

(a) Constitutional Reaction Due to Surface Radiations

In patients who have received relatively large doses such as may
be delivered by 250 milligrams of heavily screened radium applied for
fifteen hours or more, nausea and vomiting, a feeling of depression
and even prostration may occur toward the end of the treatment or
after the radium is removed. A metallic taste is often complained of.
These symptoms usually pass off within twenty-four hours. In some
instances they may last for weeks. Elevation of temperature during or
subsequent to such an exposure is unusual in our experience although
tliis phenomenon has been described by some authors. In using less
intense doses of surface radiations such as may be given for a small epi-.
thelioma of the skin, no constitutional effects are ordinarily observed.

(b) Local Reaction Due to Surface Radiations

Wickham and Degrais were the first to point out that important modi-
fications of vital tissue such as resolution of a tumor may be caused by
the surface application of the rays without the supervention of visible
inflammation. Hence, they called this action of the rays a "selective
action." Later this term was used to indicate that the rays affect cer-
tain types of cells in a "selective manner" regardless of the presence or
absence of macroscopic inflammation. Inasmuch as all vital tissue may
be affected to some extent, the term "differential action" has been pro-
posed by other authors to indicate the fact that the rays affect some tissues

103

104 RADIUM THERAPY

more markedly than others. Cohvell and Russ have suggested that the
thing irradiated is of as much importance as the rays and have proposed
the term "selective absorption." This term implies that certain tissues
absorb more rays than others. Hence "the more the rays are absorbed
the more the tissues are affected."

It is difficult to express in a single term both the complex action of
the rays and the response of the tissues.

It would appear that the rays have a "selective" or "differential"
action on vital tissue. This expression means that the rays affect cer-
tain normal tissues such as the spleen and lymphatic glands more
readily than others such as connective and elastic tissue. The rays
also affect certain tumors such as lymphosarcomata much more readily
than some other types of new growth, such as squamous cell epithelioma.

This "selective action" of the rays makes possible radium therapy in
malignancy for experience has shown that many types of malignant
tissue are more readily affected than most normal tissues.

On the other hand, the response of the tissues to the action of the rays
may perhaps best be indicated by the terms "selective reaction" and
"inflammatory reaction."

By "selective reaction" it is meant that under the influence of radium
rays abnormal tissues may undergo a retrograde metamorphosis without
visible inflammatory changes. This reaction is illustrated by the re-
sponse to radiation of certain epitheliomata, keloids and angiomata which
may sometimes retrogress and disappear without visible inflammation.

By the term, "inflammatory reaction" we designate the ordinary
changes characteristic of inflammation which may easily be produced by
radium. Inflammatory reaction usually appears between the seventh and
fifteenth day, but it may appear as early as two or three days after ex-
posure, and in some cases it may be delayed for as long a period as
four weeks.

For convenience, four degrees of "inflammatory reaction" may be dis-
tinguished, although these degrees or stages of reaction pass insensibly
into each other. These are, first — simple erythema; second — erythema
followed by desquamation; third — vesication or superficial ulceration;
fourth — deep ulceration.

We may now describe the clinical effects of radium rays upon the skin
and mucous membranes when doses sufficiently intense to produce in-
flammation with superficial destruction are used.

After the application of radium to the healthy or noninflamed patho-
logic skin, there is a latent period during which no apparent effect is
seen. The duration of the latent period depends upon the amount of
radium used, i.e., upon the intensity of the rays; the type of rays, i.e.,
whether beta or gamma rays preponderate ; and to some extent upon the
sensitiveness of the tissues. If a one-fourth strength glazed applicator
containing about 20 mg. of radium element is applied unscreened directly

THE RADIUM REACTION 105

to the skin for one or two hours, the latent period is very short — some-
times not over twelve to thirty-six hours. The beta rays form about 90
per cent and the gamma rays about 10 per cent of the total radiation from
the apparatus used in this manner. If the same apparatus is screened
with 2 mm. of lead so that only the hard gamma rays are effective and is
applied at a distance of 1 cm. for thirty hours the latent period may last
for from seven to fifteen days. Speaking very generally, the larger
the quantity of radium and the more the beta rays preponderate, the
shorter the latent period is found to be. The first evidences of the in-
flammatory reaction are slight redness and swelling of the skin which
itches and becomes tender. A crust of yellowish or greenish gray aspect
then gradually forms. Vesicles or bullse may occasionally precede the
formation of the crust. The tissues underneath the crust may be dry
or moist depending on the degree of the reaction. The crust may last
for days or weeks, sometimes falling off or being accidentally knocked
off but usually reforming several times before healing occurs. The gen-
eral appearance of a well-developed crust has been compared to that
of impetigo contagiosa. If the crust has rested on an ulcerated and sup-
purating base it becomes more and more dry as the inflammation sub-
sides. Frequently the different layers of crust become superimposed so
that a mass of dried detritus, several millimeters thick and of charac-
teristic "oyster shell" appearance results. Finally the crust may be
detached "en masse" leaving a smooth, supple, white and hairless sur-
face. The duration of inflammatory reaction may vary within the widest
limits. Reactions of the first and second degree may apparently subside
in from one to four weeks. A moderately severe reaction of the third
degree requires a period of from six to eight weeks for complete recovery.
If a severe reaction of the fourth degree has been produced, six or eight
months or even a longer time may elapse before healing occurs. In
some cases, if the reaction has been of considerable severity, attacks of
dermatitis (so-called secondary or deferred reactions) may occur at
intervals for several years, even after complete healing has apparently
taken place.

Fortunately a tendency to the development of epithelioma on the scar
tissue resulting from severe radium reactions has not been observed.
Telangiectasia frequently supervenes on the radium scar in the course
of eight or ten months after healing has occurred.

In the treatment of inflammatory skin reactions the writer has found
the following application of some benefit in relieving the subjective
symptoms: Zinci oxidi, 5; bismuthi subnitratis, 5; adipis lanae hyd., 12;
ol. olivae, 60; aq. calcis, 60. Irritating applications should be avoided. In
fact, in many cases it is best to make no local applications, but to expose
the inflamed area to the air and allow nothing, not even gauze dressing,
to come in contact with it.

106 RADIUM THERAPY

When radium is applied to the mucous membrane in sufficient doses
an appearance is produced at the end of the latent period not unlike
that caused by the application of nitrate of silver. The irradiated area
becomes at first white and later yellowish white. .At the height of a
reaction of moderate degree, a more or less dense, yellowish white, ad-
herent membrane covers the treated area, which is surrounded by a
narrow red zone of inflammation. This membrane gradually becomes
exfoliated and is replaced by epithelium which grows in from the edges.
A smooth and supple scar is usually left which is whiter than the normal
mucous membrane. Some months later, telangiectasia may occur.

Secondary or deferred reactions have not received the attention that
their importance warrants. They may appear several months or even
several years after the primary reaction has healed. They usually come
on suddenly, i.e., they develop quite fully in the course of a few days.
In some cases of epithelioma of the mucous membranes it may be difficult
to determine whether a deferred reaction or a recurrence of the growth
is present. The mucous membrane, if affected by a secondary reaction,
becomes grayish white and in a few days is covered with an adherent
membrane. A condition practically identical with that observed during
the primary reaction develops. Secondary reactions may persist for
weeks or months. Sooner or later, however, healing occurs in almost all
cases.

In a patient with a pelvic periostea! sarcoma that was treated with
very large doses, a severe primary reaction of the skin of the abdomen
developed which persisted for nearly eight months. Two years later,
upon the site of the former area of reaction, a secondary reaction de-
veloped spontaneously. This reaction which took the form of a super-
ficial ulceration accompanied by the formation of a pultaceous adherent
mass of necrotic tissue, required three months for healing.

In the therapeutic application of radium, severe reactions should be
avoided when possible. In the treatment of certain dermatological con-
ditions, however, conservative use may be made of the destructive action
of radium. In producing reactions intentionally for cosmetic purposes,
we always employ the glazed plaques. In tissues that have been sub-
jected to previous treatment such as by x-rays, cauterization, etc., a radium
reaction is likely to be atypical and healing may be deferred for months.
Such tissues should be treated with the greatest caution and not more
than one-fourth of the normal dose should be given.

Areas that have been treated with radium may be sensitive to tem-
perature changes long after healing has occurred. Many patients com-
plain also of a peculiar sensation as if ants were crawling on the skin.
All of these symptoms usually disappear in the course of a few months
but they may in exceptional instances last for years.

THE RADIUM REACTION 107

2. INTRATUMORAL RADIATION
Local Reaction Due to Intratumoral Radiations

In certain cases, as we shall describe in a subsequent chapter, radium
salts or radium emanation may be introduced directly into the substance
of tumors — "intratumoral radiation." Under these circumstances the
radioactive material is usually enclosed in metal or glass containers —
i.e., needles or ampoules. The changes in the tissues caused by the in-
sertion of minute glass emanation ampoules have been investigated by
Halsey J. Bagg. A resume of some of the results of these studies may
be conveniently given at this point.

A series of emanation ampoules or tubes was buried in normal rat
tissue of different kinds — skin, muscle, brain, testes, etc. Another series
of tubes was buried in the Flexner-Jobling rat carcinoma. Still another
series of tubes was imbedded in human carcinoma. Suitable control
experiments, undertaken to prove that the glass itself was not responsible
for the effects, were made by imbedding nonactive emanation tubes in
living tissue. Among the conclusions arrived at by Bagg were the follow-
ing: In rat carcinoma, definite histologic changes were noted two days
after the tubes were buried. Definite radium effects, such as complete
necrosis around the tubes and changes in the adjacent outlying cells,
were noted seven days after the tubes were inserted. Complete recovery
in the case of a transplanted rat carcinoma two cm. in diameter was
noted, about forty-two days after the insertion of three tubes contain-
ing 3 me. each, placed 1 cm. apart and about 5 mm. below the surface.

Lethal effects on normal tumor cells were produced by relatively small
doses of emanation, less than one me. per tube being a satisfactory dose.

An area of tissue about one cm. in diameter was effectively radiated
by each tube.

Histologically, the main effect was the production of an area of necrosis
which was surrounded by a pronounced leucocytic infiltration. The area
of effectively radiated tissue did not increase in direct proportion to
the amount of emanation in the tube. When relatively strong tubes
were used, the tissues in close proximity were radiated for a longer time
than was necessary to produce lethal effects in these cells. The rays
did not penetrate effectively, however, to a much greater distance than
the 1 cm. zone, probably because the easily absorbable beta rays were
responsible for the main effects. While the gamma ray effects from
relatively strong tubes are undoubtedly greater than those from the
weaker tubes, it was difficult to determine this point because of the
prompt reduction in size of the treated tumors. Bagg suggests that
human tumor tissue may be treated most effectively by imbedding tubes
of 0.5 inc. strength 1 cm. apart evenly throughout the mass.

108 RADIUM THERAPY

Biologic Hypersensitiveness

There is little doubt that some individuals are more sensitive to radia-
tions than others. In certain individuals, prolonged exposures with a
considerable quantity of heavily screened radium will cause marked
.constitutional effects such as -nausea and depression. In others, a similar
exposure produces little or no constitutional effect. Certain types of
skin are apparently quite radiosensitive and may react severely to an
exposure that will cause little or no effect in other types. We recognize
only a few of the conditions that render one skin more radiosensitive
than another. Among these conditions are (1) a lack of the normal
quantity of pigment indicated by the fair color of the skin; (2) absence
of the normal seborrheic oiliness. These factors seem to render the
skin more radiosensitive. Certain parts of the integument in the same
individual are also more radiosensitive than others. In general, the
mucous membrane is more sensitive than the integument. Marked idio-
syncrasies, however, are relatively rare but should always be thought of
in the beginning of a course of radiations.

CHAPTER XII

THERAPEUTIC APPARATUS

In the treatment of disease, radium may be applied in the form of
(a) radium salts, (b) radium emanation, or (c) active deposit.
The therapeutic effects of radiations from apparatus containing
radium salts, radium emanation, or active deposit are identical.

A. APPARATUS CONTAINING RADIUM SALTS

Radium salts may be placed for therapeutic use in (1) tubes, (2)
needles, (3) flat plates or plaques.

1. Radium Tubes. — Radium tubes are made of capillary glass and are
filled usually with from 5 to 50 mg. of radium element in the form of
sulphate. This is closely packed so that the salt does not move about in
the tube. The length of the tubes varies from 1 to 2 cm. and the diameter

A. B. c. D. E.

Fig. 19. — Apparatus for the application of radium.

A, Silver tube containing 15.21 mg. radium element. Length of tube 16 mm., outside diameter
2 mm., wall thickness ^o mm. B, Brass screen, wall thickness 1 mm., to contain tube A. C, Round
glazed applicator, l/2 strength, 1 cm. in diameter. D, Square glazed applicator, % strength, 2 by 2
cm. E, "Toile" wrapped in rubber dam, ^o 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 %0 mm. 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 RADIUM THERAPY

on so that the radium may be 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 sonxe strong noncorrosive alloy. The wall thickness of steel
needles is usually %o mm., .the length 2.7 em. and the outside diameter
1.75 mm. While platinum is nearly 3 times as dense as steel, and a plati-
num needle will furnish about 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 %0 of a millimeter and con-
taining 10 or 12 mg. of radium element should not be left in the tissues
over eight to twelve hours. The total amo\mt of radium element con-
tained in the needles should not be over 50 or 60 mg. unless the physician
has had the experience with the method and the cases 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. Plat Plates, or Plaques, on Which the Radium Salt is Spread. — The
plaques may be composed of linen, rubber or metal. 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
made 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 applicators may be made of any desired shape but the
surface must be flat. Attention must be paid to the degree of concen-
tration of "spread radium" as it is. evident that different effects are
produced by variations of this 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 element to the square cm. The strength of each applicator is
always approximate.

A convenient type of applicator is a square plaque 2x2 cm., and of
"half strength," i.e., containing 10 mg. of radium element. Other
plaques may be smaller or larger, round or oval, and 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

THERAPEUTIC APPARATUS 111

a thickness of %0, %o and 1 mm- are convenient. Varied proportions 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 rays.
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.

When 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 then 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.

B. 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 words, 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, however, 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 water to which a small quantity of hydi-ochloric 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 %0 or even yl(M 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 me. 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 bj" 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

THERAPEUTIC APPARATUS

113

me. of emanation. They may be made by cutting up longer emanation
tubes 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 be cut into shorter lengths with great rapidity.
The method of using the bare emanation tubes by inserting them into
the tumor tissue is described in a subsequent chapter. We have devised
an instrument for the convenient insertion of ampoules (Pig. 36).
(2) Special steel needles, devised by Joly and Stevenson, in which the

1 I

Fig. 20. — Apparatus for the application of radium emanation.

A, Capillary glass emanation tube, length 7 mm., outside diameter ^lo mm. B, Knameled silver
tube, length 1.6 cm., wall thickness fyio mm. to contain glass emanation tube A. C, Brass screen,
length 2]/2 cm., wall thickness .f>2 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 Vio 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 wall 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,
however, 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 tissues. (3) A solution of active deposit
may be used.

1. The Active Deposit Collected on Metal

We have already stated that when 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 ta 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 bulb 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
observed, 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 wire consists

THERAPEUTIC APPARATUS 115

of alpha, beta and gamma rays. Just as in the case of the piece of metal
enclosed in the emanation chamber and previously 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 Cohvoll and Russ.)

RATE

OF DECAY OF

RADIOACTIVE DEPOSIT

ALPHA

TIME

KAYS
ACTIVITY

GAMMA RAYS
TIME ACTIVITY

0 minutes

100

0 minutes 100

10 "

10 " 96.6

20 "

20 " 88.4

30 "

40 "

40 ' ' 66.9

50 "

60 "

60 " 38.5

1 hr. 30 min. 14

1 hr. 30 min. 25.3

2 hr. 00 "

7.2

2 hr. 00 " 12.9

3 hr. 00 "

1.8

3 hr. 00 " 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 coming from each apparatus be carefully measured
and directed in accordance with our knowledge of the radiation neces-
sary to destroy each normal and diseased 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 vary
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
appai'atus 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
the substance of tumors.

SURFACE RADIATIONS

Neglecting for the moment the radiosensitiveness of the tissues, the
therapeutic effect of radiations depends upon their quality, their intensity
and the duration of the exposure. The quality of the radiations depends
upon the filtration. The intensity of the radiations at a given point
depends upon:

1. The quantity of radioactive material.

2. The filtration.

3. The shape of the source, i.e., the method of distribution of the
radium on the apparatus.

4. The distance from the source.

5. Absorption in the apparatus and in the tissues.

6. The secondary radiations in the tissues.

A marked variation of any one of these factors naturally alters

116

DOSAGE 117

the effect of the radiation. We may now consider the effect of each
factor.

(1) The Quantity of Radium or Radium Emanation in the Apparatus

It is evident that, other things being equal, the larger the quantity of
radioactive material the more intense is the radiation. Speaking very
generally the quantity of radium used naturally depends upon the pur-
pose of the radiation, i.e., whether the lesion requires a mild or intensive
dosage and whether superficial or deep effects are desired. The quantity
used varies therefore from a few milligrams which may be suitable for
superficial cosmetic disorders of the skin to one gram or more which may
be necessary for influencing deeply seated or extensive malignant tumors.
Tt has already been stated that experience has shown that tubes and
plaques containing from 5 to 50 milligrams of radium element or tubes
containing the same number of millicuries of emanation are the most
convenient and useful. Almost any combination of apparatus to aug-
ment the amount of radium for a single case may be employed. Com-
binations of apparatus to increase the quantity of radium and therefore
the dose are made in accordance with certain mathematical calculations
and as the result of experience in dealing with special kinds of lesions.

It must be especially emphasized that while there is probably an opti-
mum dose and method of treatment, equally good results may be achieved
in many cases by very different methods. The various factors mentioned
above that enter into the effect of the radiation may all differ with dif-
ferent operators and yet the final result may be equally good. Wickham
long ago insisted upon the fact that we cannot be too dogmatic, or use a
too "cut and dried" method in matters pertaining to radium therapy.
In children, the dose should not be more than one-half and in the case of
very young children not over one-fourth of the normal dose for adults.

(2) The Filtration

We have discussed in a previous chapter the use of metallic and non-
metallic screens to filter out or absorb types of radiations that are some-
times undesirable before they reach the skin. In routine practice, the
metal screens over the radium vary in thickness from 0.1 mm. to 2 mm.
while the nonmetallic material used, in addition, may vary from 1 mm.
to 1 or more cm.

In general, when superficial effects are desired, little or no metal
screening may be used from a theoretical point of view, as the first centi-
meter of tissue absorbs practically all the beta rays. Although under
these circumstances, both beta and gamma rays take effect, the quantity
of beta rays greatly exceeds that of gamma rays while their absorption
takes place readily; therefore their action greatly preponderates in short
unscreened exposures. Great care must be observed, however, in using a
preponderance of beta rays on the skin, as painful burns may be easily

118 RADIUM THERAPY

produced. It is seldom wise to use varnish or glazed apparatus or bare
emanation tubes without a certain amount of metal screening unless the
operator has had experience with the method.

When deep effects are desired, all of the beta rays and some of the
softer gamma rays should be absorbed by a screen of brass 2 mm. thick
or by its equivalent of another metal. Only the hard gamma rays are
thus effective in penetrating the screens and affecting the tissues.

The reason for the use of thick metal screens, in the treatment of
deeply situated tissues is thus very evident. If an unscreened radium prep-
aration is used, the greater part of the radiation, consisting of beta rays,
will be absorbed by the superficial layers of tissue. As a result of this
absorption, the superficial layers may receive an amount of rays sufficient
to destroy them while the deeper tissues will receive relatively little
radiation. On the other hand if screening of sufficient thickness, such as
may be furnished by two millimeters of brass, is used, the superficial and
deep layers of tissue may receive approximately the same amount of
radiation. As many types of tumor cells are more sensitive to the rays
than normal cells, the purpose of the radiation, i.e., the destruction of
tumor cells and the preservation of the normal cells may be accomplished.

TABLE XIV

This table shows the ionizing effect due to beta and gamma rays in air. At the
same distance (1 cm.) if absorption is not considered, the ionization due to beta rays
may be assumed, according to Eve "s experiments, to be thirty-four times that due to
gamma rays. We may also accept Eve's values for the coefficients of absorption, i.e.,
for beta rays .012; for gamma rays, a value so small as to be negligible.

The table illustrates the effect of a filter of sufficient thickness to absorb all but
gamma rays in causing a diminution of the total intensity.

DISTANCE IN
CENTIMETERS

EFFECT

BETA RAY

GAMMA RAY

TOTAL

3360

100

3460

830

855

365

376

203

210

128

132

Let us now consider the effect of

(3) The Shape of the Source and
(4) The Distance of the Source from the Surface

From a theoretic point of view, the radium preparation may be dis-
tributed on an applicator of almost any desired shape or size. Thus,

DOSAGE 119

radium emanation may be concentrated at one or more points or lines;
radium salts may have a linear distribution, as in the case of tubes, or
they may be spread uniformly over plates of various shapes and sizes.
Practically, we limit ourselves to the use of tubes (i.e., a linear distribu-
tion) containing either radium emanation or salts, and to the use of
round, square or rectangular plaques of various sizes containing radium
salts.

It may be shown by mathematical calculation that the difference be-
tween the effect due to a linear distribution (i.e., a tube several milli-
meters long) and that due to a point is not more than a fraction of 1 per
cent at a distance of several centimeters. The orientation of the tube at
these distances is also unimportant.

We are concerned chiefly, therefore, with the effect of tubes and of
plaques which may be used singly or in combination. We may now con-
sider the variation in intensity of the radiations at different distances
when the source is

(a) A single point, or a line several mm. long, i.e., a single tube.

(b) A number of points or lines, i.e., several tubes.

(a) Single Tubes

Considering each tube as a point source, the variation of the concentra-
tion of the rays with distance is in accordance with the law of inverse
squares, i.e., the intensity of the rays varies inversely as the square of
the distance from the source, any effects of absorption being, for the
moment, neglected.

Let us assume that we have a source of gamma rays (filtered to absorb
beta rays) so small that it may be considered as a point. Let this source
be situated in a medium such as air which does not appreciably absorb
the gamma rays. We may consider the point as a source of radiant
energy which is emitted equally in all directions.

If we assume that a sphere of unit radius is drawn about the point
source as a center, all of the radiation will go through the surface of this
sphere. As there is nothing to distinguish one portion of the spherical
surface from another, we can assume that the energy passing through a
unit area of such a surface is a measure of the intensity at that distance
from the point.

Now suppose the unit area is moved out to a distance of two centimeters.
It is now part of the surface of a sphere of area 4ir(2)2 instead of
4 IT (I),2 i.e., of a surface with four times the area of the first sphere.
The energy that passed through the spherical surface of radius 1, must
now pass through the spherical surface of radius 2, but it will be spread
over four times the area over which it was previously distributed. Hence

120 RADIUM THERAPY

the amount of energy passing through the unit area, which we have taken
as a measure of the intensity, is just one-fourth, at a distance of 2 cm.
from the source, of the intensity at a distance of 1 cm. from the source.
Similarly, at a distance of 3 cm., it is % of the intensity at 1 cm. ; at
4 cm., %0 arid 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 standpoint of homogeneity of radiation, it is frequently
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 rays would receive on the far side, which is 6 mm.
distant, %6, i.e., (%2) 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
% (i.e. 52/102) 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
desired 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 duration
of the exposure or both of these factors must be made.

When the radium tube is introduced into a small cavity such as the
interior of the uterus, it 'is, of course, seldom possible to keep the tube
more than a few millimeters distant from the tissues. Under these cir-
cumstances, the tissue nearest the tube receives a dose that is frequently
excessive but in this particular situation no ill effects are ordinarily ob-
served. On the skin, however, an unnecessary and undesirable reaction
would be produced if the radium tube is in too close apposition to it. As
has been stated before, when very superficial effects are desired, the
radium tube may be placed in relatively close contact with the tissue.
Great care must be exercised under these circumstances, however, not to
prolong the duration of the exposure beyond the proper limits, as a pain-
ful burn may be easily produced. As we have seen, when deeper effects
are desired, the radium tube may advantageously be placed at least a
few millimeters away from the lesion or several tubes may be used simul-
taneously at a distance of several millimeters or centimeters, so as to

DOSAGE 121

cover the area occupied by the lesion. The latter arrangement, which is
ordinarily the better one, will be considered in a subsequent section.

It may be found by experiment that fifty millicuries, contained in a
point or minute tube, screened to absorb all but gamma rays will pro-
duce, at a distance of 1 cm., an erythema of the skin in twelve hours,
i.e., 600 me. centimeter hours. (50 x 12.)

Let us assume the permissible skin dose to be 600 me. centimeter hours.
"We can now find, at least theoretically, the smallest distance from the
skin at which, for example, a fifty millicurie tube can be left for an hour.
This is easily done as follows, if we consider the tube as a point source :

The intensity at any point at a distance r from the source is — ~ "We

wish this intensity, when multiplied by the time in hours (1 in this case)
to be equal to 600.

Hence = 600 r2 = yi2 r = %V3 = .29 cm.

or approximately 3 mm. Actually the tube can be placed closer than
this, since a tube is not a true point source. The intensity at .29 cm.
away is not 600 but is given by

2-^ tan* ' " being eclual to
~Tf~ ~zf zero in this case.

where M is number of millicuries in the tube, I its length, / the distance
away. Take M == 50, I = .7, / = .29. We get for the intensity at .29 cm.,

100 -1 .7

tan . , or 433.

.7(.29) .58'

This is about two-thirds of that permissible. Hence to approximate to
the possible distance, try .29 V% = -236 cm. The intensity at that dis-
tance is

100 -1 .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, with the same intensity, the effect
is the same, this will also be the minimum permissible time to leave a
25 me. tube for two hours, a 100 me. tube for one-half hour, etc., since
25 x 2 == 100 x Y2. The above rule holds, however, only within certain
limits as we shall show later on.

(b) Several Tubes

Let us now consider two 50 me. point sources. Let us try to give
three points on the skin the same amount of radiation. Let us take one

122

RADIUM THERAPY

X ^ '

k X S '

\ X S '

D C £

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, D, 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-

50 50

tensity at C due to A is -r^. That at C due to B is -— - . Now AC = BC

BC2

if the midpoint of DE is C. Hence the total intensity at C is
100

2 x 50
AC2

AC2'

Let

= T. DE = X

Then A C == A D X D C = T2 +_

100

2? 1

= 600 or T2 + =

X' 46

T' -I

50 50

The intensity at D due to A is A n2 or — . The intensity at D due to

AD2

B is

—. . The sum of these two intensities is to

be 600.

BE f DE

= 600 or

= 12

"We have therefore two equations.

+ _ = 1/6

= 12

We can solve these for X2 and Y2 and hence 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 the distances as given, the intensity at J> and E amounts to 482.
Hence we must approximate as before by decreasing the distances in the
ratio V%- By several such approximations (we need here to correct the

ratio -~^ - as well as V AD and \/AB together) we arrive at the values.

\/AB
Distance from skin = .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 square. The
results are given in Table XV.

TABLE XV
THEORETIC MINIMUM PERMISSIBLE DISTANCE FROM SKIN FOR 50 MC. FOR ONE HOUR

POINT SOURCES TUBES 7 MM. LONG

DISTANCE FROM DISTANCE DISTANCE FROM DISTANCE

THE SKIN APART SKIN APART

Single

tube

.289

cm.

.235

cm.

Two

tubes

.333

1 1

.471 cm.

.289

1 1

.440

cm.

Three

.353

1 1

.612 "

.312

1 1

.307

1 1

Four

1 1

.375

1 1

.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 for - .,. ,

(Distance)2

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
V6 etc.

TABLE XVI

THEORETIC MINIMUM PERMISSIBLE DISTANCE FROM SKIN FOR 50 MC. FOR Six HOURS

Assuming the maximum permissible (lose as 50 me. at 1 cm. for 12 hours, the minimum

permissible distances for 50 me. 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 empha-

124 RADIUM 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.

Prom the foregoing, it may be stated that, in general, two equal sources
or tubes may be placed with their centers approximately twice as far
apart as their distance from the skin. This arrangement provides an
approximately uniform field of radiation at the skin sui'face. The fore-
going rule does not hold, however, in the case of large extended sources
as we shall show 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.

It is evident that as the number of tubes is increased the effect approaches
very closely to that produced by a plaque, i.e., by a uniform distribution
of the radioactive material on a plane surface. At a distance of a few
millimeters, the plaque source has a slight advantage over the multiple
tube source in that the former produces an approximately uniform field
of radiation. This uniformity of effect is of considerable importance in
the treatment of cosmetic skin disorders, such as angiomata. At a dis-
tance of several centimeters, both types of apparatus have an almost
identical effect.

We may now give some illustrations of the relative effects of a few dif-
ferent types of applicators. For convenience, the gamma ray intensity
derived from a point source containing one mg. of radium element at a
distance of one centimeter, is taken as the unit in all of the following
calculations.

In calculating Table XVII each tube was considered as a point. The
calculation was also made for 25 tubes considering each tube as a
line; the result was 9.941, a difference from 9.946 of %0 per cent.

The intensity decreases as the number of tubes increases, approaching
the value for a uniform distribution which may be estimated from the
above table as approximately 9.8, i.e., a difference of only about 2 per

DOSAGE

125

TABLE XVII

EFFECT or DIFFERENT NUMBERS OF TUBES CONTAINING A TOTAL QUANTITY 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 KAY INTENSITY AT A
6 CM. FROM THE PLANE

POINT ON THE AXIS,
OF THE TUBES

13.88

10.31

9.99

9.95

100

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 the skin.

Tables XVIII 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 RADIATION DUE TO A CIRCULAR PLATE 4 CM. IN DIAMETER AND
A POINT SOURCE, RESPECTIVELY. 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

cm.

74.8

5000

1 1

57.7

1250

1 1

47.7

555

40.7

313

1 1

35.4

200

1 1

31.1

139

27.7

102

..8

1 1

25.4

1 1

22.3

1.0

1 1

20.1

1.2

t (

16.6

34.7

1.5

12.8

22.2

1.6

1 1

11.8

19.6

2.0

8.67

12.5

2.5

6.17

8.00

4.0

2.79

3.13

6.0

1 1

1.32

1.39

8.0

< t

.76

.78

10.0

1 1

.49

.50

126 RADIUM THERAPY

shown, the 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

INTENSITY OF GAMMA RADIATION DUE TO A CIRCULAR PLATE 10 CM. IN DIAMETER AND
A POINT SOURCE, RESPECTIVELY. 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 CIRCULAR PLATE 10 CM. POINT SOURCE

THE SOURCE FROM IN DIAMETER CONTAINING CONTAINING 500 MG.

THE SURFACE 500 MG. RADIUM ELEMENT RADIUM ELEMENT
(ABOUT 6.36 MG. PER SQ. CM.)

cm.

65.2

500

4 t

39.6

125

t t

26.6

55.6

t t

18.8

31.3

((

13.9

t t

8.24

10.2

I I

4.46

5.0

t I

2.11

2.22

1.21

1.25

.784

.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 were 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 the 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 tubes or plaques each containing
50 mg., than a single powerful tube, containing 500 nig.

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 distribution 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)2) 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 which 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 BAY INTENSITIES DUE TO A SINGLE 6x6 CM. PLATE, CONTAINING 200 MO. IN
12 TUBES. ABSORPTION IN THE APPARATUS Is NOT CONSIDERED.

DISTANCE

FROM AXIS

DISTANCE
12 TUBES

FROM PLATEz=6 CM.
POINT SOURCE

DISTANCE FROM
12 TUBES

PLATE=10 CM.
POINT SOURCE

cm.

4.845

5.556

.898

2.000

1 1

4.503

5.000

.833

1.923

1 1

3.670

3.846

.665

1.724

1 1

3.202

3.279

.557

1.600

1 1

2.775

2.778

.441

1.471

1 1

2.022

2.000

.208

1.220

1.493

1.471

.998

1.000

1 1

1.128

1.111

.821

.820

i (

.875

.862

.679

.676

i (

.693

.685

.566

.562

.556

.475

.472

.463

.459

.403

.400

128

RADIUM THERAPY

TABLE XXI
GAMMA KAY INTENSITIES DUE TO Two SUCH PLATES, OR POINTS, IDENTICAL WITH

THOSE IN THE PREVIOUS TABLE. DISTANCE PROM SOURCE TO SURFACING 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

DISTANCE APART

CENTER LINE

OF PLATES =

OF PLATES ==

CM.

PLATES

POINTS

PLATES

POINTS

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 SURFACED CM.

DISTANCE PKOM

DISTANCE APART

CENTER LINE

OF PLATES =

2 CM.

6 CM.

10 CM.

PLATES POINTS

0 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

inflammation is ordinarily produced and in most cases it may be avoided al-
together.

For certain of the most superficial effects, the radium may be placed
practically in apposition with the skin or mucous membranes, especially, as
we have shown, when the source of the 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 cm. ; for the deepest effects, from 6 to 10 or more cm. As the distance

DOSAGE

129

of the source from the surface increases, the quantity of radium necessary
for certain effects must be increased. "While the diminution of intensity
due to distance and absorption may be partly compensated for by in-
creasing the duration of the exposure, massive deep effects cannot be pro-

TABLE XXIII.
METHODS OP CALCULATING ABSORPTION IN THE APPARATUS

Absorption coefficient = .05.

By one method, i. e., treating the absorption of the radiation from each point sepa-
rately, one gets for the intensity due to 500 mg. in 25 tubes, at a point on the axis 6 cm.,
distant from the plane of the tubes, G.32. By a second method, i. e., using the average
distance, 6.28.

Sample calculation.

NO. TUBES

EFFECT DUE TO EACH

TOTAL EFFECT

FIRST METHOD

-(-! + . 3)
.555e , =.372

.372

.SOOe .330

.660

.385e —IS" .243

.486

.SOOe .330

.660

.454 e i" .295

1.180

-(.i+V~)

.357e u- .222

-d+ W)

.384e '" .242

.888
.484

.357e !« .222

.888

.294e .176
SECOND METHOD

d d

.704

6 . 322
nd

6 6

2V~10 6.3246

25.298

2V~13~ 7.2112

28.845

2VTT C.C332

26.553

2V TT 7.4834

59.868

2VT? 8.2462

-.45906
9.941e =6.281

32.985

25)179.528

20)7.1812

.35906
.1

.45906

The difference between the results of the two above methods is 2/3 per cent. Ordi-
narily it would be much less as in these calculations a small distance has been used.

130 RADIUM THERAPY

duced 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 cases, 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 XXIV for a medium of about
the density of wood, which has an absorption coefficient of approxi-
mately .05. There are two possible ways of calculating the effect of absorp-
tion on the radiation due to a number of tubes, as shown in Table XXIII.
By 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 affected 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
separate!}', or, using the average distance for all the tubes at once, we mul-
tiply the uncorrected value by the exponential e-^d, where /* is the coefficient
of absorption, d the thickness of absorbing material in question. As we
have said before, /* is takeu as ^o = .05 in Tables XXIII and XXIV. The
absorption factor due to filtration is taken as e- -1.

TABLE XXIV

GAMMA RAY INTENSITY DDE TO A CIRCULAR PLATE 10 CM. IN DIAMETER, CONTAINING
500 MiM.KiKAMS RADIUM ELEMENT AT A POINT ON ITS Axis,

CONSIDERING ABSORPTION

This is compared with the intensity due to a point source containing the same

quantity of radium.

DISTANCE OP THE SOURCE
FROM THE SURFACE

INTENSITY DUE TO
PLATE SOURCE

INTENSITY DUE TO
POINT SOURCE

1 cm.

57.6

475.6

2 "

33.4

113.1

3 "

21.5

48.4

4 "

14.6

25.6

5 "

10.3

15.6

7 "

5.6

7.2

10 "

2.6

3.0

15 "

.99

1.05

20 "

.44

.46

25 "

.22

.23

DOSA<;K

131

The conclusions to be drawn from Table XXIV are (1) that absorption
in the apparatus cuts down the intensity due to a distributed source
more than it does that due to a point source ; this is, of course, self-
evident in any case, since the distributed source is under the conditions
taken (point source taken at center of disk, and effect on axis considered)
on the average farther away than the point source. Thus the effect on
the axis at a distance of 10 cm. differs by 11 per cent without consider-
ing absorption, 13 per cent if absorption is considered, the advantage
being with the point source in each case. (2) That if 20 still be the
maximum skin dose possible, the point source can now be put about 4.5
cm. from the skin, the extended source 3.2 cm. (previously 5 and 3.8)
i.e., the superiority of the latter in this respect is increased. The in-
tensity 5 cm. below the skin surface for the same skin dose of 20 is now
15 per cent greater for the plaque source than for the point source and
about the same (15 per cent) at a point 10 cm. below the skin surface.

TABLE XXV

GAMMA RAT INTENSITY DUE TO SINGLE 6x6 CM. PLATE CONTAINING 200 no., RADIUM

ELEMENT IN 12 TUBES, EVENLY DISTRIBUTED ON THE SURFACE. ABSORPTION

IN THE APPARATUS Is CALCULATED BY THE APPROXIMATE METHOD

PLATE

SOURCE

PLATE SOUECE

APPROX-

POINT

APPEOX-

POINT

EXACT

METHOD

IMATE

SOURCE

IMATE
METHOD

SOURCE

METHOD

C CM. AWAY

10 CM. AWAY

AND ON AXIS

3.180

3.178

3.724

AND ON AXIS

1.028

1.097

2 cm. from axis

2.914

2.912

3.298

2 cm. from axis

.985

.983

1.045

A I t It It

2.295

2.276

2.426

4 tt tt 1 1

.872 .870

.910

5 " " "

1.960

1.940

2.008

5 " " " .801

.797

.828

g « « it

1.639

1.613

1.644

6 " " " .725

.720

.743

g 1 1 1 1 1 1

1.119

1.099

1.098

8 " " " .576

.571

.582

10 " " "

.763

.748

.743

10 " " " .446

.442

.446

12 " " "

.528

.5] 8

.514

12 " " " .342

.338

.340

24 tt it it

.374

.368

.364

14 " " " .262

.258

.259

16 " " "

.271

.266

.264

16 " " " .201

.199

.198

18 '< " "

.199

.198

.195

18 " " " .155

.153

20 ' ' " ' '

.150

.148

.146

20 " " " .120 .119

.118

The advantage of a distributed source over a point source at the
same distance from the point being treated is evidently not more than
3 per cent, at any point, and really the point seems to be the better for
this case as near the axis it gives a value higher by 15 per cent for 6
cm. distance. The whole advantage of the distributed source lies in this
latter fact, however, since this means that the point must be farther away
in order that the intensity on the axis be such as not to burn the skin
near by. In other words, for the same intensity on the axis, the intensity
6, 8 or 10 cm. off the axis is 15 or 20 per cent greater for the greater

132

RADIUM THERAPY

number of tubes. The field is more uniform,
the advantage does not appear so great.

For the 10 cm. distance,

TABLE XXVI

GAMMA RAT INTENSITIES DUE TO Two 6x6 CM. PLATES, EACH CONTAINING 200 MO.
IN 12 TUBES AT A DISTANCE OF 6 CM. FROM THE COMMON PLANE

DISTANCE TROM

DISTANCE APART

CENTER LINE

OF PLATES

0 CM.

4 CM.

8 CM.

1 cm.

5.209

3.934

2.758

3 "

4.819

4.033

3.058

5 "

4.033

3.943

3.442

7 "

3.058

3.442

3.554

9 "

2.167

2.669

3.185

11 "

1.493

1.910

2.494

13 "

1.034

1.318

1.789

15 "

.727

.896

17 "

.524

2 CM.

6 CM.

10 CM.

0 cm.

4.590

3.278

2.238

2 "

4.553

3.414

2.402

4 "

4.299

3.677

2.823

6 "

3.677

3.708

3.288

8 "

2.823

3.288

3.451

10 "

2.013

2.566

3.113

12 "

1.390

1.838

2.445

14 "

0.962

1.269

16 "

0.678

Hence, absorption in the apparatus being considered, a nearly uniform
field will be obtained for the primary rays at a distance of 6 cm. from
the skin surface when the radioactive plates are a little less than 4 cm.
apart.

TABLE XXVII

GAMMA RAY INTENSITIES DUE TO Two 6x6 CM. PLATES EACH CONTAINING 200 MG.
IN 12 TUBES AT A DISTANCE or 10 CM. FROM THE COMMON PLANE OF THE TUBES

DISTANCE FKOM
THE CENTER LINE

DISTANCE APART
OF PLATES
0 CM. 4 CM. 8 CM.

1 cm.

1.857

1.597

1.301

3 "

1.753

1.561

1,315

5 "

1.561

1.471

1.323

7 "

1.315

1.323

1.286

9 "

1.063

1.130

1.186

11 "

.834

.926

1.027

13 "

.644

.724

.861

15 "

.493

.561

17 "

.378

DOSAGE 133

TABLE XXVII — CONTINUED.

DISTANCE FROM DISTANCE APART

THE CENTER LINE OP PLATES

2 CM. 6 CM. 10 CM.

cm.

1.744

1.450

1.152

1 1

1.710

1.448

1.168

t <

1.604

1.428

1.210

< t

1.428

1.366

1.243

1 1

1.210

1.243

1.229

1 1

.983

1.073

1.140

.777

.880

.992

1 1

.598

.696

.458

Hence, considering absorption in the apparatus, a nearly uniform field
will be obtained for the primary rays at a distance of 10 cm. from the
skin, when the radioactive plates are about 6 cm. apart.

(b) Absorption in the Tissues. — We may now discuss the effect of
absorption in the tissues in decreasing the intensity of the radiations
below the skin surface. In order to estimate the effect of absorption
we may compare (1) the superficial dose, i.e., the intensity of the radia-
tions at a given point on the surface of the skin and (2) the deep dose,
i.e., the intensity of the radiations at a given point at different depths in
the tissues.

Let us assume that 500 mg. of radium element screened with 2 mm. of
lead and contained in 25 point sources is arranged uniformly on a plate
(plane surface) 10x10 cm. and is placed so that the radium is 6 cm.
distant from the surface of the skin. Let us also assume an absorption co-
efficient of .01 between the plate and the skin surface. The intensity
at the surface of the skin on a line perpendicular to the center of the
plate is then 7.19.

Under the same conditions, assuming an absorption coefficient for the
tissues of .05, the intensity at a distance of 6 cm. below the surface (12
cm. from the plate) will be 1.65; 10 cm. below the surface (16 cm. from
the plate) it will be .72; 12 cm. below the surface (18 cm. from the plate)
it will be .57.

Under identical conditions, but assuming that the radium is placed
at a distance of 10 cm. from the skin, the superficial dose (i.e., the in-
tensity at a point on the surface) will be 2.299 while the deep dose (i.e.,
the intensity at a point 10 cm. below the surface or 20 cm. from the
plate) will be .50.

From the above, it may be seen that, with the source 6 cm. from the
surface, the ratio between the superficial and deep dose at a point 10
cm. below the surface is about 1 to 10; with the source 10 cm. from the
surface, 1 to 6. The ratio of the superficial doses in the two cases is 7
to 3 ; the ratio of the deep doses about 7 to 5. From the standpoint of

134

RADIUM THERAPY

Curves for eikct Jue 1o fwo6^6^m p/ofe>,

Lath 2£Q try in 12. tuh&
Distance vi point horn common [Ion. 10 uv
Disfoace opai Tot phtei mc/icafed torcmh
curve

( 7 8 7 /p //

22. — Graph illustrating Table XXVII.

/.?

equalizing the deep dose and the superficial dose, this comparison shows
the advantage of placing the source at a considerable distance from the
surface. Of course, the method of treatment from the greater distance
has the disadvantage of requiring a larger quantity of radium or a
longer exposure. It is evident that it is impossible also to put the source
at a distance sufficiently great to make the superficial dose and the deep
dose from primary gamma rays equal because of the absorption in the
tissues. The decrease in intensity with distance from the source is also
very marked. These difficulties may be minimized or overcome by using
several portals of entry.

DOSAGE 135

Multiple Portals of Entry

The intensity permissible at the surface, as we have already said, can-
not l>e pushed down into the depths of the body unless more than one
portal of entry be used. In order to deliver, with one portal of entry,
an intensity beneath the surface approximating that at the surface, the
rays should be made as nearly parallel as possible, i.e., the plate must
be placed at a considerable distance from the skin. Under these cir-
cumstances, the resulting intensity at every point in the tissues is rela-
tively low; consequently either a large amount of radium or a treat-
ment of long duration must be used. Moreover, the absorption in the
tissue, though somewhat modified by the secondary effects, is bound to
diminish the intensity below the surface to a certain extent. For strictly
parallel rays, the diminution amounts to from %(> to ^o of the total
intensity per centimeter; the same, or slightly more, for rays not strictly
parallel, (divergent or convergent beams). For the latter type of rays,
the diminution in intensity due to the inverse square law must be taken
into account; and in addition, in any case, the augmentation due to
secondary rays produced in the tissues must be considered.

In order to determine the number of portals of entry necessary in a
given case, one should know, if possible, the ratio between the suscepti-
bilities of the parts that one does not wish to injure and of those that one
wishes to destroy. It is then necessary to determine at what points the
portals of entry can be placed; i.e., one must consider the contour of the
skin surface as related to the position of the region to be treated. The
only remaining requisite theoretically necessary for a complete determi-
nation of the portals of entry is a knowledge of the intensity due to the
radioactive source used at given distances, above or below the skin
surface.

For certain very special conditions, one can obtain the desired relations
quite readily, but in the general case it is, of course, a very hard if not
impossible task to find the best possible arrangement, although ordinarily
one can get a usable solution and therefore one sufficient for the purpose.

Let us take, for example, a very special case. Suppose a tumor situated
at a point 10 cm. below the skin is to be radiated and that we wish to
treat it with radium placed at a distance of 10 cm. above the surface.
To make the problem as easy as possible, we may also assume the skin
surface to be a circle, having a radius of 10 cm. about the point P, which
is to be treated. (Fig. 23.) It is necessary to determine the ratio of the
field at S on the surface of the skin, to that at P, when a certain quantity
of radium is placed at A, 10 cm. from 8 on the line P 8 produced. If
absorption be neglected and the radium be taken as a point source, the in-
tensity at S is, from the inverse square law, - "Or^— - where M is the

A S 100

136

RADIUM THERAPY

number of millicuries of radium emanation used.
M M

The intensity at P is

similarly

i.e., just % of that at S.

A P2 400 '

Hence, at first sight, in order to make the intensity at P equal to that
at 8, one would say that it is necessary to have four portals of entry, situ-
ated at A, B, C, and D, the effects of which would all combine at P making
the intensity at point P equal to that at point 8. We find, however, four
portals are insufficient since B, C, and D contribute not alone to the effect
at P but also to that at 8. Let us then try five portals. This number
proves to be insufficient, and so on up to nine or more portals of entry.

•B

Fig. 23. — Diagram illustrating multiple portals of entry.

It should be theoretically possible, by sufficiently increasing the number
of portals to obtain an intensity at P which would be greater in relation
to that at 8 than the ratio of the carcinoma dose to the skin dose. Actually
the number of portals can be made fewer by using portals outside one
plane, and by suitable screening.

Let us suppose that all radiations are screened off except, for each
portal, a beam just sufficient to radiate the tissue to be destroyed (as-
suming no sideways scattering). Then the four portals required by

DOSAGE 137

theory will be enough, provided they are placed so that the overlapping
of beams occurs almost entirely in the diseased tissue, i.e., the portals
should not be diametrically opposite as in Fig. 23. It is then possible
to place the portals much nearer together. They must be sufficiently
far apart, however, so that the four beams do not overlap nearer the
portals than the tumor at P, or even that three beams do not overlap
except in the immediate vicinity of the tumor.

Let us now place an applicator containing 1000 inc., arranged on a
plate (10 x 10 cm.) at a distance of 10 cm. from the skin. Let us assume
that the maximum skin dose is obtained by applying it for eighteen
hours, i.e., 18000 me. 10 cm. . hours (1000x18). Actual experiments
have proved this latter assumption to he nearly correct. The maximum
skin dose is thus found Tinder the conditions stated to be 180 me. cm.

h°U™-

Assuming the ratio of 1.15 of skin dose to carcinoma dose, as deter-
mined by Kroenig and Friedrich to be correct, the carcinoma dose that
it is necessary to deliver 10 cm. below the surface at a point which we
will assume to be the site of the tumor, is 156 me. cm. hours. This dose
can be delivered theoretically with four portals of entry, by giving at
each portal a radiation that is slightly less than the maximum skin dose.

The above result is easily calculated from the following considerations.
According to the inverse square law, the intensity at a distance of 20
cm. is Y4 of that at 10 cm.; hence in order to make the intensity mul-
tiplied by the time product at a distance of 20 cm. the same as that at
10 cm., we must use four different sites of application. The sum of the
effects at each portal on the skin will then be equal to the total effect
on the tumor.

The above calculation assumes that there is no absorption in the tis-
sues. If we assume an absorption coefficient of .05, the effect due to each
portal will be decreased in the deep dose by e'°-r>; hence, since the sur-
face dose is unaffected, the number of portals of entry must be increased
by e°-5 i.e., 4 e-~' or in other words, about 6 portals will be the number
required.

It is possible, however, that the effect of "scattering" the primary
beams, i.e., the effect due to secondary radiations, nearly cancels the
effect of absorption.

Deep Dose Produced with X-Rays Compared with that Produced with

Gamma Rays

With x-rays, the problem of delivering the deep dose is even more
difficult in some particulars than with gamma rays, because of the in-
ferior penetrating power of the former. Hence, whatever can be ac-
complished with x-rays can also be done with gamma rays providing the
amount of radium necessary to produce the required intensities is avail-

138 RADIUM THERAPY

able. If intensities at the skin surface comparable with those producible
with x-rays can be produced with gamma rays, the intensities in the
depths of the tissues will be far greater when radium is the source of
the radiations.

It is the product of the coefficient 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 with 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 with the former.

TABLE XXVIII

RELATIVE INTENSITIES AND EFFECTS DUE TO PARALLEL BEAMS OF X-RAYS AND GAMMA

BAYS RESPECTIVELY

It is assumed that the effects of the absorption of equal quantities of both agents are

equal.
Assume that the absorption coefficient for x-rays=0.13; for gamma rays=0.033.

DISTANCE

X-RAYS
INTENSITY

EFFECT

GAMMA
INTENSITY

RAYS
EFFECT

.13

.033

.88

.11

.97

.032

.77

.10

.93

.031

.68

.088

.90

.030

.59

.077

.87

.029

.52

.068

.84

.028

.46

.060

.82

.027

.40

.052

.79

.026

.35

.0 (0

.77

.026

.31

.040

.74

.025

.27

.035

.72

.024

.24

.031

.70

.02.1

.21

.027

.67

.022

.18

.024

.65

.022

.021

.63

.021

.14

.018

.61

.020

.07

.009

.52

.017

.04

.005

.44

.015

(1) Hence, for the same 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 cm. depth. (2) For the same effect at
the surface, however, the intensity and effects at any point below the
surface are much greater for gamma rays than for x-rays.

The first of the above statements merely has to do with the relative
strengths of each source to be used. The second is of importance as re-
gards the number of sources (i.e., of portals of entry) necessary, and the

DOSAGE 139

possibility of increasing the dose at points below the skin to a greater
value than at the skin.

It is the ratio of the deep dose to the surface dose that determines the
number of portals of entry necessary.

In order to make the dose at a depth of 10 cm., equal to that at the
surface, at least four portals of entry are needed for the type of x-rays
considered, while two are more than sufficient for the gamma rays. At
a depth of 15 cm., eight portals of entry for x-rays, and still only two
for gamma rays are necessary. Two portals will still suffice for gamma
rays at a depth of 20 cm., while fifteen are needed for x-rays.

It must be emphasized that the above comparison assumes that the
beams from both types of sources are parallel.

6. Secondary Radiations

Let us now consider the effect of the secondary radiations in the
tissues in augmenting the intensity of the radiations below the skin
surface.

It was formerly believed that the relative intensity of the rays in the
depths of the tissues, as compared with the 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 deep intensity, the secondary radiations re-
sulting from the impingement of the primary radiations upon the tissues
must be taken into account. Gudzent comes to the conclusion, in a con-
sideration of this topic, that the simple absorption 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 compare the
absorption of the rays in water with the absorption 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. Our 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 diminution 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 subsequent section.

The term "milligram hours" or "millicurie hours" was introduced by
Dawson Turner to express the duration of the exposure. By these terms,
we designate a number which is obtained by multiplying the number of
mg. of radium element or of millicuries of emanation by the number of
hours of exposure. We may neglect for the moment the decay of the
emanation. Thus, 10 mg. or 10 inc. 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 surface radiations, unless the other known factors that
enter into the dose, i.e., the screening, the shape of the source and
especially 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 very 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,
however.

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 for one hour, and one milligram contained in a similar
tube and applied for 100 hours, will give different effects and yet the
number of mg. hours of exposure — i.e., 100 — may be said to have been
given in both cases. The biologic changes in the tissues during the
longer exposure are probably responsible for the difference in the ob-
served effect.

This brings up the question of whether 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 equal 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 intensity. Accord-

DOSAGE 141

ing to these authors, therefore, if we assume this statement to hold for
radium, it may be roughly estimated that 20 mg. applied for ten hours
would give approximately the same biologic effect as 100 mg. applied
for two hours, provided the other conditions of the application are iden-
tical. In both cases, 200 mg. hours would be the calculated dose. On the
other hand, 20 mg. applied for ten hours would give a less intense effect
than 200 mg. applied for 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 not the same for large variations of the time and intensity.
It should be possible, however, to determine more accurately the biologic
effect of variations of these two factors 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 substantially 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 which 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 mg. hours were given.

Millicurie Hours

While the number of "milligram hours" may be easily found by mul-
tiplying the number of mg. used by the number 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 that interval. This is shown in Table XXIX.

TABLE XXIX

TIME OF APPLICATION
IN HOURS

VALUE, I.K., NUMBER OP MILLICURIES
NECESSARY TO START WITH IN ORDER
TO HAVE MEAN VALUE OF 100

100.4

100.75

101.1

101.5

101.9

102.3

102.65

103.0

103.4

103.8

104.2

104.55

104.95

105.3

105.7

106.1

106.5

106.9

107.3

107.7

108.1

108.5

108.9

109.3

111.6

114.2

116.5

119.1

In most cases it is sufficient to take the reciprocal of the value which
the strength will take at the middle of the period of application. Thus
for 48 hours to take

100 100

i.e.,

value present 24 hours later ' e - ;

or, approximately, -=— = 6/5 x 100 = 120

O/D

This holds more 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 used. 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 rubber dam in which it is
wrapped, of from three to five minutes. Such exposxires should not be
repeated more than.two or three times in the course of a week.

Such treatments are adapted to superficial skin diseases.

For skin disorders 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 four hours 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 me. 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 cm. 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 tubes containing radium salts or tubes
of radium emanation may be used. For influencing deeply seated tumors,
exposures lasting from ten to thirty 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 me. is necessary in most cases; in other cases not less than
1000 mg. or me. should be employed. If 500 mg. or me. are used, a

144

RADIUM THKRAPY

total exposure of 25 hours at a distance of 6 cm. may he given in two or
more periods. At a distance of 10 cm., a total exposure of 36 hours may
he given in two or more periods. With 1000 ing. or me. under the same
conditions, 12% hours may he given at a distance of 6 cm. ; 18 hours
at a distance of 10 cm. If emanation is used, duo allowance must he
made for its decay. The exposures may ho given in two or more periods.

INTRATUMORAL RADIATIONS

In some cases, as has heen said before, the radioactive material may
be inserted directly into the tumor tissue. Radium salts in 'metal needles
may be used for this purpose or radium emanation contained in metal
needles or glass ampoules may he employed. I usually prefer radium
emanation in glass ampoules.

At the present time, the exact dosage employed in metal needles is
largely a matter 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 each containing as much as 10 me. of emanation may he

TABLE XXX

SUGGESTING DOSES (.T ANEW AY) THAT MAY BE USED WHEN BARE EMANATION AMPOULES

ARE INSERTED INTO TUMORS

FOB CIRCULAR AND APPROXIMATELY OVAL TUMORS OP THE SAME LONG DIAMETER

DIAMETER

DEEP INKII.TK

ATION

SURFACE

ABXA

DOSAGE

cm.

sq.

cm.

5 me.

(4 cm.

1.7

* t

1 1

8 '

cm.

3.14 "

t i

10 '

2% cm.

Not more

than

1% cm.

4.8

t t

1 1

15 '

(

cm.

Between

and

2 cm.

6.5

t I

t 1

17.5

me.

cm.

Between

and

2 cm.

12.5

1 t

cm.

Between

and

2% cm.

19.3

( t

< (

22.5

t I

cm.

Between

and

3 cm.

28.2

t i

t t

FOR SPHERICAL TUMORS THERE IS LITTLE DIFFERENCE

DIAMETER

AREA OP PLANE
OF DIAMETER

NO. OF CUBIC
CEN-TIMETERS

DOSAGE

1 cm.

.77

sq. cm.

.52 c.c.

5 me.

1% cm.

7.7

1 1 ti

1.70 "

8 "

2 cm.

3.14

it 1 1

4.18 "

10 "

2% cm.

7.8

1 1 n

8.19 "

15 "

3 cm.

6.5

n 1 1

14.08 "

20 "

4 cm.

12.5

1 1 1 1

33.44 "

22 "

5 cm.

19.3

it tt

65.29 "

25 "

6 cm.

28.27

1 1 ft

112.86 "

30 "

7 cm.

38.48

1 1 1 1

251.52 "

35 "

8 cm.

50.26

it it

40 "

DOSAGE 145

left in the tissues six -hours. In all eases needles should not be inserted
nearer to each other than 1 to 2 cm. Prior to Bag'g's experiments, which
have already been referred to, the dose used in the insertion of the glass
emanation ampoules was larger than we now employ. This aiithor's
experiments have shown the advisability of using relatively small doses.

In dealing with smaller growths, it is sometimes advisable to increase
the dose suggested by Bagg. We frequently employ in treating the
smaller growths 5 me. 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 inc. per c.c. of tissue may be sufficient, when the
total amount of emanation equals from 25 to SO me. When the latter
quantity of emanation is used, a larger amount of '.'cross firing" from
the different tubes naturally takes place than when smaller quantities
of emanation are employed.

Methods of Decreasing and Increasing the Radiosensibility of Tissues.
—The question naturally arises whether it may be possible especially in
deep therapy to make the skin more insensitive and the tumor more
sensitive to the radiations. 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 compression of the surface by thin wooden plates and
showed that the skin was able to stand without injury doses of radium
that otherwise injured it. H. E. Schmidt and others have confirmed this
observation. Reicher and Lenz have suggested that a diluted adrenalin
solution be injected into the skin hi order to render it anemic. Chris-
toph Mueller-Immenstadt has used high frequency currents for the
same purpose. He states that this procedure 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. Gauss and Lemcke, Mueller-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 Goldstuecker radiated trypanosomes which 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 researches may widen the scope of these ex-
periments. Up to the present time, however, the attempts at desensitizing
the skin and sensitizing the tumor 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 apparatus 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 shoiild 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

Fig. 24. — This photograph shows the method of handling radium. A radium tube is being inserted

into a screen.

the thickness required in order to keep the radium at the proper dis-
tance may then be applied and held in place by adhesive tape or a
bandage.

The radium plaques or tubes, singly or in combination, may then be
laid upon the material covering the lesion and held in position in the
same way.

Protection from the discharges from a moist lesion is always assured
for the apparatus by wrapping it in a finger cot or dental rubber dam.

146

TIIK TKCHNIC OF RADIATION

147

In the treatment of a lesion of the mucous membranes, the tubes 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 affords a relative amount of protection
that is ordinarily sufficient. It must be remembered that if the radium

Fig. 25. — Forceps 30 cm. long for handling radium tubes.

tube is held at a distance 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 inverse 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,
wo 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 different 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 handling 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 pliable 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

THE TKCHXIC OF RADIATION

149

also fastened to the neighboring 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, we insert a finger cot which may be distended with
air by a catheter. In this case, also, distance protects the healthy, bal-
looned out, mucosa.

For some years, especially in mouth 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 accessible and the
tubes may be laid in little troughs in the compound. By this device,

Fig. 28. — Screen holders. 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 fingers to come in contact with the radium tubes.

the tubes may be held in position without much discomfort to the pa-
tient for the required length of time.

The amount of radium to be used in superficial treatments naturally
varies with 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.

Fig. 29. — Same apparatus as in Fig. 28 but of smaller size. .

When dealing with larger superficial growths on the skin 200 or more
milligrams may be required. The radium may be 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 Avise to use
less than 200 milligrams of radium element or me. of emanation.

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 daily or on
alternate days or twice weekly, 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% 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 than from 2 to 3 cm., was
widely accepted.

According to the earlier observations of Wickham and Degrais, radium
rays may penetrate effectively to a depth of at least 9 cm.

Kroenig has recently stated that it is possible to radiate successfully
a carcinoma of the cervix uteri through the abdominal wall, i.e., the

THE TECHNIC OF RADIATION

151

rays 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 effectively to a depth of from 14 to
16 cm. It is evident that Bumin'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 Bumin's
cases, his conclusions were 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. 31. — Tandem gold screens for holding one or more enamel emanation tubes. These
screens have a universal thread so that a radioactive rod of any desired length may be made. The
proximal end of the apparatus is attached to a long flexible silver wire. Length of each screen 2
cm., outside diameter 4 mm., wall thickness 0.8 mm.

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 mm.

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 walls 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 tube.

On the other hand, if a quantity 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 will 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 with 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

•-

Fig. 34. — Radium pad composed of "squares" of soft wood. The interinr uf die package is
stuffed with cotton. Dimensions of pad IQxlO'xlO cm. Fifteen screens containing radium emana-
tion tubes are held in position on the pad by adhesive plaster. This type of apparatus is used for
deep gamma radiation of large tumors.

emphasized that, for adequate deep effects, a considerable quantity of
radioactive material must be used — preferably not less than from 500 to
1000 or more milligrams of radium element or millicuries of emanation.
In some cases, 2000 nig. or me. are desirable. While the relatively slight
intensity from smaller quantities, such as :500 milligrams, can be to some
extent compensated for by prolonging the exposure, practical experience
has shown that in most cases the best effects are obtainable only by using
the larger quantities for a shorter time.

THK TKCHNIC OF RADIATION

153

For the treatment of deeply seated tumors or other pathologic tissues,
when the overlying 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

IMR. 35. — The upper photograph 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 he withdrawn when the required exposure has heen 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 he engaged in the groove
on the end of the instrument. Traction on the needle may then be easily nuide without damage to
the tissues.

packages. On account of the joints formed by the tape, even the larger
pads have a certain degree of flexibility. On these packages or pads the
tubes are placed in parallel rows or in accordance with any desired ar-
rangement. The tubes may be held in place by strips of adhesive tape.

Fig. 36. — Author's instrument, constructed on the plan of an ordinary syringe, for burying
emanation ampoules. The obturator, sliding in the lumen of the needle, enables one to eject the
ampoule intu tin- tumor tissue.

The size of these large packages varies in accordance with the lesion
to be treated. We frequently use packages having the dimensions of
6x6x6 cm. or 10x10x10 cm. (See Fig. 34.) In order to reduce the
weight of the larger wooden packages and to minimize the amount of gamma
ray absorption in the applicator, we fill the center of each package with
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 THEHAl'Y

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. — Heavy cast-iron movable shield for the protection 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. Otherwise some sort of a shield should 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, abdomen, pelvis, etc., are present, there should be used for the
radiations not less than 500 to 2000 or more milligrams or millicuries.
The radium should be placed at a considerable distance, e.g., ten or more
centimeters from the 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 distribution of the radium,
its distance from the skin, etc., may thus be fulfilled. In addition, every
area of skin from which the tumor can be attacked should be homo-
geneously radiated as we have just described.

F>y 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 exposure is correct.

Employing 1000 mg. distributed over an area of 100 sq. cm. and placed
at a distance of 10 cm. 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 weeks later, should not consist of over 5000 me.
or mg. hours. These doses were suggested by Janeway and Failla and
they accord in a general way witli 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. Great care should
be employed therefore in applying and removing sticking plaster in
such areas.

(b) "INTRATUMORAL" RADIATION

(1) The insertion of radium salts or radium emanation 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 order that repair may be accomplished.
(4) The quantity of radium embedded in a growth depends upon the size
of the tumor and the thickness of the needle wall and to some extent upon
the situation of the growth. Encapsulated organs, such as the tonsil and

156 RADIUM 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 Memorial Hospital in New York, by Kelly and his as-
sociates in Baltimore, by the writer and many others.

The glass emanation ampoules that are used are ordinarily about tln-ee
millimeters long and 0.3 mm. in diameter. They may be inserted into the
tumor in proper cases and allowed to remain in situ. Over !)() 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% days, by the number of millicuries originally in the tube. AVe 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 sharp 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 manner. After insertion into the tumor
tissue, the needle should be withdrawn a few millimeters just before
the plunger ejects the ampoule so that the danger of breaking the am-
poule by forcing it against the tissue is obviated. One may also withdraw
the needle simultaneously with the pushing in of the plunger. The
ampoule thus rests in the minute cavity formed 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 this method, I am of the
opinion that this danger is negligible if the technic is correct.

The following suggestions may be observed in the insertion of tire-
ampoules: — Aseptic precautions must be used; each ampoule should not
contain more than three millicuries of emanation; the ampoules should
be inserted about one cm. apart; care should be taken not to implant
them near large vessels, nerve trunks, bones or thin-walled viscera; if

THE TECHNIC OP RADIATION 157

possible to avoid it, the ampoules should not be inserted into healthy
tissues.

A zone of necrosis forms around each ampoule a week or more after its
insertion. Healing occurs in from four to eight weeks and in favorable
cases a smooth cicatrix is left.

The quantity or dose of radium emanation to be used in intratnmoral
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. The 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 been de-
scribed.

In some cases, the two methods, intratnmoral radiation and deep
gamma radiation, may be advantageously combined.

CHAPTER XV

RADIUM IN GENERAL SURGERY
A. MALIGNANT TUMORS

Carcinomata exhibit different degrees of radiosensibility. Adler has
tried to determine whether this difference in sensibility depends on the
histologic structure of the tumor. According to this author's investiga-
tions, rapidly growing carcinomata 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-
cinomata, 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 would
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 robust condition is much
more susceptible 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 earcinojnata 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, however, in all probability are
also at work in determining the response of the tumor to radiations.

158

RADIUM IN GENERAL SURGERY 159

(a) Operable Malignant Tumors

Janeway has raised the question of the advisability of treating pri-
marily with radium certain eases 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-
able growths should be 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 with
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 number of years. Radium, 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 impossible 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 rays 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 cells are
four to seven times as sensitive as most normal cells. According to
Friedrich and Krocnig'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 words, 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 RADIUM THERAPY

slightly more radiosensitive 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
with radium a change in the growth that 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 lias already taken place. In such cases, palliation is all that ca7i
ordinarily be hoped for, although the primary growth can occasionally
be healed by radium.

We may now refer to the radium treatment of malignant disease oc-
curring in different situations in the body.

THE TREATMENT OF CARCINOMATA

For convenience of description we may group together carcinomata
affecting the different organs.

1. Epithelioma of the Skin

The problem of treatment of epithelioma of the skin depends to a
great extent upon the type of growth that is present.

(a) Squamous-cell Epithelioma

If the case is considered operable by the surgeon and the adjacent
glands are palpable, the draining lymphatic glands and gnnvth may be
excised "en bloc." If the glands are not palpable, operation may be
limited to the growth and radiation given to the glands. There is little
doubt, however, that even in distinctly operable cases, preoperative
radium treatment will be of advantage. At the time of operation, emana-
tion ampoules may be buried in the operation field. After operation,
prophylactic radiations should also be given. Over dosage should be
guarded against. With an early diagnosis, recovery should be brought
about in at least 95 per cent of the cases.

Inoperable cases of squamous-cell epithelioma may frequently be re-
tarded in their progress for considerable periods of time and in some
instances a clinical recovery may be brought about. The diagnosis of
squamous-cell from basal-cell epithelioma is frequently impossible with-
out a microscopic section and as it is often inadvisable to obtain this a

RADIUM IN. GENKRAt:;SUR^E:RY 161

few of the clinical points of difference may be indicated. (1) Its loca-
tion. Epitheliomas of the lower lip, tongue, penis and extremities are
usually of the squamous-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) Rapidly growing epi-
theliomata with metastases to the adjacent lymphatic glands are prac-
tically always of the squamous-cell type.

It must be emphasized, however, that there is no absolute rule holding
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 with 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 growths, it is
best to use only gamma rays. In some cases two hundred millicuries,
screened with two millimeters of brass and arranged so that it is con-
centrated in the proportion 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 weeks, 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. Great care should be
taken to avoid "burns" which 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
eases. This procedure, however, causes considerable inflammatory re-
action and if unsuccessful precludes for a time further treatment in most
cases on account of the pain. We prefer, therefore, the former method
in ordinary cases but in some cases we resort to the unscreened glazed
applicators. In some cases bare emanation ampoules may be buried in
the growth. For the prophylactic treatment of the adjacent lymphatic
glands powerfid deep radiations are advisable. Four hundred millicuries
(5 me. per square cm., 2 mm. screen, 6 cm. distance) may be applied 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 we possess and sometimes succeeds when
everything else fails. In spite of some statements to the contrary, we be-
lieve that this type of epithelioma is one of the most amenable of all
types of new growth to radium. Failure may, of course, occur in very
extensive cases in which the loss of tissue is very great and repair is

162

RADIUM THERAPY

Fig. 38. — Epithclioma of right cheek.

RADIUM IN GENERAL SURGERY

163

Fig. 39. — Patient in Fig. 38 after radium treatment.

164

RADIUM THERAPY

Fig. 40. — Epithelioma of right side of nose.

RADIUM IN; GENERAL SURGERY

165

Fig. 41. — Patient .in Fig. 40 after radium treatment.

166

RADIUM THERAPY

Fig. 42. — Epithelioma of tip of nose.

RADIUM IN GENERAL SUKGERV

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. — Patient in Fig. 44 after radium treatment.

170

KADHJM THKRAl'Y

Fig. 46. — Epithelioma of right inner canthus, eyelids and nose.

RADIUM IN GENERAL SURGERY

171

Fig. 47. — Patient in Fig. 46 after radium treatment.

172

KAD1UM THEKAI'Y

Fig. 48. — Epithelioma of left inner canthus, eyelids, nose, cheek and upper lip.

RADIUM IN GENERAL, : SURGERY

173

Fig. 49. — I'aticnt in Fig. 48 after radium treatment.

174

RADIUM THERAPY

Fig. 50. — Epithelioma of the right temple

RADIUM IN GENKRAL SURGERY

175

31. — Patient in Fig. 50, after radium treatment.

176

RADIUM THERAPY

Fig. 52. — Epithelioma of the left temple.

RADIUM IN GENERAL SURGERY

177

Fig. 53. — Patient in Fig. 52 after radium treatment.

378

RADIUM THERAPY

Fig. 54. — Kpithelioma of left malar region. Patient referred by Dr. Joseph Scheurich.

RADIUM IN GENERAL SURGERY

179

Fig. 55. — Patient in Fig. 54 after radium treatment.

180

RADIUM THERAPY

Fig. 56. — Epithelioma of forehead.

RADIUM IN GENERAL SURGERY

181

Fig. 57. — Patient in Fig- 56 after radium treatment.

182

KADIUM THERAPY

Fig. 58. — Epithelioma of right ear.

RADIUM IN GENERAL SURGERY

183

Fig. 59. — Patient in Fig. 58 after radium treatment.

184

RADIUM THERAPY

Fig. 60. — Epithelioma situated below right ear and involving ear lobe.

RADIUM IN GENERAL SURGERY

185

Fig. 61. — Patient in Fig. GO after radium treatment.

186

RADIUM THERAPY

Fig. 62. — Epithelioma of nose, left eyelid, cheek, and upper lip.

RADIUM IN GENERAL SURGERY

187

Fig. 63. — Patient in Fig. 62 after radium treatment.

188 RADH'M TI1KKAPY

almost impossible. In a few cases, there seems to be a laek 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
long periods, frequently do badly. The method of application in the
basal-cell type of epithelioma is similar to that used for squamous-cell
cancer. Treatment of less intensity is usually sufficient, however.

When dealing with very small and superficial growths, one may use a
quarter-strength applicator screened with VJ,, mm. of lead and in close
contact with the skin for six or eight hours in several periods of one or
two hours each. In treating larger, deep-lying growths, we follow the
plan previously indicated for the more grave type of sqmnnous-cell epi-
theliomata but shorter exposures are adequate, as a rule, to bring about
resolution and healing. In certain cases, the use of b;irc emanation am-
poules which jn-e inserted into the edges of the epithelioma is advisable.

In the treatment of epithelioma supervening on sear tissue due to pre-
vious exposure to x-rays, very cautious and light treatment should be
given. Not over one-half the amount indicated above as suitable for
ordinary cases should be used, ;is experience has shown that the previ-
ously treated tissue breaks down very easily and the ulceration caused
may heal with the greatest difficulty. The scar following radium treat-
ment, even in extensive cases, is usually smooth and supple and very
inconspicuous. Contractures seem never to occur, a point of the great-
est importance in treating lesions about the eyelids. When ectropion has
resulted from previous operations, it may sometimes be lessened by ra-
dium treatment. I have treated with radium over one thousand cases
of basal-cell epithelioma of various clinical types and failure to bring
about recovery has been uncommon.

(2) Epithelioma of the Nasal Mucosa

Epithelioma in this situation :nay be treated by carrying the radium
tubes attached to a long silver wire through the anterior nares into the
nasal passage. The same technic may be employed for sarcoma and
lymphosarcoma of the cavity of the nose and nasopharynx. One hundred
millicuries contained in two tubes, arranged end to end, screened with
one millimeter of silver and one or two millimeters of rubber may be
used in periods of one to three hours each for a total exposure of 6 hours.
In certain cases, bare emanation ampoules may be successfully buried
in the epithelioma.

(3) Epithelioma of the Lip

Epithelioma of the lower lip comprises about one-half of the cases of
epithelioma. It begins most frequently at the junction of the mucous
membrane and the skin. It may begin, however, either on the cutaneous
or mucous surface of the lip. It is usually of the squamous-celled type.

RADIUM IN GENERAL SURGERY 189

Speaking very generally if the lesion is less than a centimeter in diameter
and is not deeply infiltrated, radium may be used alone with expectation
of success in selected cases. Larger lesions should be treated by pre-
operative radiation and excision. Postoperative radiation is always
advisable.

In the application of radium to the growth, the usual technic consists
in the use of not less than 200 to 300 me. This may be screened with
1 mm. of silver plus 2 mm. of rubber. One should radiate an area extend-
ing several centimeters beyond the visible disease. Certain tumors should
be attacked from the superior, the internal and the external aspect of
the lip. Six hundred me. hours may be given to an area of 4 square
centimeters. This technic produces sharp reaction.

If the adjacent lymphatic glands are not palpably enlarged, they may
be left undisturbed by the surgeon but should receive heavy prophylactic
gamma-ray radiation. If the adjacent glands are palpably enlarged,
conservative surgical removal may be undertaken in selected cases. The
operation may be pi-eceded and followed by surface radiation. In some
cases bare emanation ampoules may be buried in the operative field fol-
lowing removal of the lymphatic structures or in the glandular masses
in case they are not removed but merely surgically exposed.

(4) Carcinoma of the Lingual, Buccal and Pharyngeal Mucous

Membranes

While epithelioma of these structures is frequently refractory to ra-
dium, very good and even brilliant results may sometimes be obtained.
The most notable advance in the treatment of cancer in these situations
consists in the use of bare emanation ampoules which are inserted into
the tumor in the manner previously described and allowed to decay in
xilii. When surface applications are made, we would advise the use of
not less than 200 millicuries. The radium should be screened with 1 milli-
meter of silver and 2 millimeters of rubber. An exposure of five hours in
divided doses may be given. For holding the radium in position we fre-
quently utilize the dental composition material suggested by Janeway.

At the present time, in suitable cases, we invariably bury bare emana-
tion ampoules in growths of the accessible mucous membranes.

Leukoplakia

It must be remembered that patches of leukoplakia may disappear
spontaneously if tobacco is discontinued.

The radium treatment of leukoplakia, which is such a frequent pre-
i-iirsor of epithelioma of the lingual, buccal and pharyngeal mucous mem-
branes, is often successful. A caustic dose must often be employed in
order to bring about the desired result, but at times deeper and less
caustic radiations may be given. A method that we have frequently

100

RADIUM THERAPY

Fig. 64. — Epithelioma of lower lip.

RADIUM IN GENERAL SURGERY

191

Fig. 65. — Patient in Fig. 64 after radium treatment.

192

RADIUM THERAPY

Fig. 66. — Epithelioma of upper lip.

RADIUM IN GENERAL SURGERY

193

Fig. 67. — Patient in Fig. 66 after radium treatment. The insertion of false teeth gives the mouth a

distorted appearance.

194

If \Dir.\l THKKAI'Y

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

Fig. 70. — Carcinoma of the tongue in patient aged 65 years. Patient referred by Dr.

Photograph taken July 7, 1921.

P. Berg.

RADIUM IN GENERAL SURGERY

197

Fjg. 71. — Patient in previous figure after insertion of 19 millicuries of radium emanation con-
tained in 15 bare glass ampoules. Photograph taken July 15, 1921. Six months later patient
;i].prartd clinically well.

198 RADIUM THERAPY

used consists in the application of 80 millicnries concentrated in the
ratio of 10 millicuries per square centimeter. This may be screened with
1 millimeter of silver and 2 millimeters of rubber. A total exposure of
eight hours in periods of one or two hours each may bo 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-ccll 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, palliation 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 were inserted into the growth for thirteen and one-half
hours, and seven weeks later 72 milligrams for twelve hours. Hay ward
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 advantageously combined with the method of
burying bare glass emanation ampoules. The greatest care must be used
not to give an overdose and produce sloughing. It must not be forgotten
also that healing can only occur when a bed of healthy tissue capable
of producing 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 frequently yields to radium and sometimes
displays a marked susceptibility. If metastases from a tonsillar growth
are present in the neck these growths are also more than ordinarily sen-
sitive to the rays. If 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. Radium 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 millicuries screened with the equivalent of 2
millimeters of brass and 2 millimeters of rubber may be applied for three
hours in periods of one hour each. The intensity of the treatment to be

RADIUM IN GENERAL SURGERY 199

given naturally depends upon the extent of the disease. If the growth
projects several millimeters above the level of the normal mucous 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 bare 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

Many cases respond favorably to radium treatment. The disease most
often begins at the alveolar process of the jaw. Carious teeth are usually
found in these cases and the disease may apparently have started around
one of them. The antrum is usually invaded early by the growth. Metas-
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 any case it is not wise to allow the antrum cavity to
remain closed. By means of long silver wires carrying the tubes, the
radium may be brought into direct contact with the growth. In addition,
heavy treatment may bo 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 me. with the same screening may be used for five hours.
Externally, 250 me., screened with 2 mm. of brass and arranged on a pad
covering 50 sq. cm., 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 combination 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,
radium is introduced into the antrum cavity.

(6) Carcinoma of the Inferior Maxilla and Floor of the Mouth

Cancer of the lower jaw usually 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. 72. — Carcinoma of right superior maxilla involving antrum. I'hotograph taken January, 1915.

HAD1UM IN GENERAL SURGERY

201

Fig. 73. — Patient in Fig. 72 after radium treatment. Photograph taken April, 1915.

202 RADIUM THERAPY

huccal mucous membrane. When metastases to the neck 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 treatnicnl. 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 lie given. Instead of surface applications, several bare
ampoules may then be buried in the lesion ; 0.5 me. to 1 me. 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-
tons 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, phafyngeal, lingual
or laryngeal mucous membrane. The supraclavicular glands are fre-
quently involved in mammary cancer. The primary 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-
layed 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 burying bare emanation ampoules. Sometimes a com-
bination of these methods is most desirable. Isolated and movable glands
may be removed surgically prior to radium treatment. 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
distance of 6 centimeters. Concentrated in the ratio of 5 to 10 millicuries
per square centimeter and screened with the equivalent of 2 millimeters
of brass, an exposure of twenty-five hours in several periods of ten or
more hours each may be given. If metal needles are inserted, 5 to 75

RADIUM IN GENERAL SURGERY 203

millicuries in steel needles that have a wall thickness of 0.4 mm. may
be buried for twelve or eight hours. If bare emanation ampoules are
buried in inoperable masses, a dose of 0.5 to 1 me. or more per cubic centi-
meter of tumor tissue may be given. Considerable judgment must be exer-
eised 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 for. Individual masses of glands that have some de-
gree of mobility and are 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 areas of normal tissue, which may add to the patient's
discomfort and hasten his end.

Douglas Quick has recently described the procedure used at the 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 me. of radium emanation in
bare glass ampoules are embedded 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 author are encouraging.

(b) Carcinoma of the Thyroid Gland

Some cases of this disease are strikingly benefited. The technic of
treatment should be wholly by external or surface radiations. Burying
emanation needles in these tumors may result in an intractable fungating
growth. Powerful deep radiations must be used. Six hundred milli-
curies screened with the equivalent of 2 millimeters of brass and in the
ratio of 5 to 10 millicuries per square centimeter may be applied at a
distance of 6 centimeters. A total exposure of twenty hours in periods
of ten or more hours each may be given. Metastasis to the bones or other
organs may take place several years .after apparent recovery.

In carcinoma, endothelioma, and certain mixed parotid tumors, en-
couraging results have been obtained. In tumors containing cartilage
not so much effect is to be anticipated. The technic may consist of the

204 RADIUM THERAPY

application of 250 millicuries at a distance 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 he given. As
in all other tumors, the teehnic varies with 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 following 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
may 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 previoiisly
reported by the writer.

In intrinsic carcinoma of the larynx, radiation from the outside or
inside of the larynx may be employed. Kelly and Burnam have referred
to several cases treated by external radiations that have recovered and
remained well for varying periods. Ordinarily, however, the combination
of internal and external treatment is necessary for success. It is doubt-
ful whether external radiations alone are sufficient to cause complete
regression. G. B. New of the Mayo Clinic has treated intrinsic carcinoma
of the larynx in the following manner: "Tracheotomy is first performed
and after cocainization 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 patients are not benefited, very encouraging results
and remarkable relief have been obtained. One man had an extensive
carcinoma of the larynx obstructing the glottis so that it was necessary
to do a tracheotomy; he was swallowing fluids only. In two months
time he had gained forty-eight pounds in weight and could eat anything.
He had a cork in the tracheotomy tube. The growth did not recur

RADIUM IN GENERAL SURGERY 205

locally but the patient died of chest metastases about fourteen months
later. However, the treatment gave 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
the chapter devoted to a consideration of the use of radium in laryn-
gology. 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 hours. During intralaryngeal treatments the throat must be kept
free of saliva by an electric suction pump.

(9) Carcinoma of the Esophagus

In this all but hopeless disease the results of radium treatment in_a
number of cases have been encouraging. Among those who have reported
their results, some of which have been favorable, are Abbe, Exner,
Einhorn, Finzi, Hayward Pinch, Janeway, Mills and Kimbrough and
the writer. Abbe reported 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-r;iys 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 that had been maintained for three years when
the case was reported. 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 writer's cases, treated in conjunction with Dr. John
A. Cavanaugh, apparent recovery was maintained for about one year
when the patient died suddenly of cerebral hemorrhage.

Technic of Treatment of Carcinoma of Esophagus. — Previous to under-
taking treatment, careful localization of the growth is all important.
Skiagraphs with and without a bismuth meal, direct esophagoscopy and
measurements with bougies usually afford sufficient information. It is
necessary that the lumen of the growth admit a bougie several milli-
meters in diameter in order that the properly screened radium may pass
completely within the stricture. In some cases, several days prior to the
treatment, a silk thread may be swallowed by the patient. The bougie
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 me., screened with 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 me. 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 by the patient and the
lower end is pulled out through the gastrostomy wound. A series of
several radium tubes is Ihen attached to the oral end 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 me. 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-
rhage, 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 subsides, 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 recurrent- carcinoma of the stomach and intestines it
is permissible to use radium in the hope of retarding the disease and
relieving pain. Janeway has seen improvement follow a combination of
posterior gastroenterostomy and radium treatment. After the above
operation was performed, several radium tubes were pulled into place
through the gastrostomy wound by means of a string previously swal-
lowed. We have used a similar 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 hoped for in these conditions. Symptomatic
improvement has been noted following powerful, deep treatment to the
abdominal wall. The condition demands the use of at least 500 me. 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 me. per square centi-

RADIUM IN GENERAL SURGERY 207

meter. At a distance of 6 cm. an exposure of twenty-five hours and at a
distance of 10 cm. an exposure of thirty-six hours may be given in periods
of ten or more hours each.

(11) Carcinoma of the Rectum

Considerable experience has been accumulated 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 carcinoma in close proximity to the anal region is less
easily influenced than the other types. A number of cases of complete
regression of the growth and apparent clinical cure persisting for vary-
ing periods of time have been reported by different authors. The per-
centage of clinical recoveries is not over 10 per cent. It 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-
proved. In borderline cases, radium treatment may render operation
possible.

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 by introducing the tubes attached to a long silver
wire into the rectum. In other cases, bare emanation ampoules may be
buried in the growth. These methods may also be combined.

Carcinoma involving a segment of the rectal wall 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 the 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, the tubes must be 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 growth in order to protect
relatively the normal mucosa. In other cases, the normal rectal wall
may be packed off by means of a rubber 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 radium employed varies with different operat-
ors. Hayward Pinch has used 50 me. screened with 2 mm. of lead and
2 mm. of rubber. An exposure of thirty 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 RADIUM THERAPY

absent. I favor, ordinarily, the use of a much larger quantity of radium.
Many cases may be treated with 200 me. screened with 2 mm. of brass
and 2 mm. of rubber 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. In 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 me. screened with 2
mm. of brass may be applied at a distance of 1 cm. The concentration
may be in the ratio of 10 me. 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
may 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. Unfortunately 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 tirethra may be 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 within the
urethra or from the external aspect. The growth may also be reached
by radiations from tubes placed along the anterior vaginal wall. Care
must be taken not to overexpose the urethral mucous membrane. As it
is impossible as a rule to introduce into the urethra a tube covered with
sufficient rubber tubing to give an adequate distance of the radium from
the growth, a burn of the urethral mucous membrane may be easily
caused without producing marked retrogression of the growth. One
hundred me. contained in two tubes arranged end to end, screened with
0.5 mm. of platinum and 2 mm. of rubber may be introduced into the
urethra for five hours 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

RADIUM IN GENERAL SURGERY

209

separated with gauze during the treatments in order to avoid a burn
of these structures. Through the anterior vaginal wall, the growth
may be radiated with 200 me. The concentration of the emanation may
be 10 me. per square centimeter and the screening 2 mm. of brass.
The distance should be not less than 1 cm. An exposure of fifteen
hours may be given divided into several periods. The radium may be
held in the vagina by means of a long silver wire which may be bent
to the required angle and fastened with adhesive tape to the anterior
abdominal wall. In some cases bare radium emanation tubes may be
buried in the growth. The dose of 0.5 to 1 me. per cubic centimeter of
tumor tissue may be used. The different methods of treatment just de-
scribed may often be advantageously combined.

(13) Carcinoma of the Prostate Gland

Benefit is frequently to be noted from radium treatment of this con-
dition.

Fig. 74. — AdenoepttheKoraa of the prostate.

The Technic of Treatment of Carcinoma of the Prostate. — Formerly the
radium contained in a hollow sound having a wall thickness of 1.5 mm. was
introduced into the urethra and allowed to remain in contact with the

210

RADirM THERAPY

growth. At the same time, another tube was introduced into the rectum in
order to "cross fire" the carcinoma. While encouraging results have been
obtained with this method, no plan seems to be so uniformly successful as
that suggested by Barringer. The essence of this method consists in
strong central radiation of the prostatic mass.

This author uses 50 me. of radium emanation, contained in the distal
1% inches of the lumen of a special gold or steel needle, four to six inches
long. Sufficient screening is obtained by the thin wall of the needle.
Under local anesthesia, the needle is introduced through the perineum
and allowed to remain six hours in each prostatic lobe. If necessary, the

Kig. 75. — Same lesimi as in Fig. 74 after radium treatment. Young connective tissue, with newly

formed vessels.

needle, guided by a finger in the rectum, can be pushed into the seminal
vesicles. In thirty cases treated by Barringer, marked retrogression of
the growth followed in every case.

Good results have been obtained by a similar method that I have out-
lined. This consists in the use of eight or more steel needles each con-
taining about twelve milligrams of radium element or millicuries of
radium emanation. These are introduced into the prostate either through
a perineal or supnipubic incision in such a manner as to radiate homogene-

RADIUM IN GENERAL SURGERY 211

rnisly the entire prostate. One of the writer's cases in which great im-
provement followed has been reported by R. H. Herbst. The needle in-
troducer illustrated in this report was devised by Dr. 0. T. Freer. In
carcinoma of the prostate, the general method of needling is the one that
promises to be of most value. The method of attack should be adapted
to the situation of the growth. Hence, either the suprapubic or the
perineal route or both routes may be chosen. The insertion of bare em-
anation ampoules gives promise of good results.

(14) Carcinoma of the Bladder

Operable Cases. — In dealing with operable cases of carcinoma of the
bladder, postoperative radiation is advisable.

Inoperable Cases. — Inoperable carcinoma of the bladder may some-
times be treated successfully with radium. Prior to the use of radium,
fulguration is sometimes advisable in order to check the bleeding. The
permanent cessation of hemorrhage and the disappearance of cystitis
and all subjective symptoms may sometimes be observed as a result of
radium treatment. Growths of considerable size may retrogress and
ulcerated areas may become covered with healthy epithelium as shown
by cystoscopy.

Technic of Treatment of Carcinoma of the Bladder. — Radium may be
applied to bladder growths either by way of the urethra or through a
suprapubic cystotomy wound. Accurate application to the growth is
absolutely essential for success. It is worse than useless to apply radium
blindly by means of an ordinary rubber catheter to the interior of the
bladder. Special instruments have been devised by Barringer, Corbus,
Kanavel, Young, and others for applying the radium through the urethra.
Barringer has devised long applicators which may be used in the sheath
of a Brown-Buerger operative cystoscope. Young has also devised spe-
cial instruments for applying radium through the urethra. By means of
these applicators, the radium may be held against the growth. Dr. A.
B. Kanavel has devised a radium-containing capsule which is provided
with a spring clip at one end. One or more capsules may be introduced
through an operating cystoscope and attached, in suitable cases, by means
of the clip to the surface of the bladder growth. With this device, treat-
ments lasting for any number of hours may be given. The capsule may
be removed by means of a silk thread which has been previously attached.
The dosage in inoperable carcinoma of the bladder varies with the char-
acter of the case and the tecluiic that is employed.

Application through the Urethra. — If the radium is applied via the ure-
thra to the surface of the growth, 100 millicuries, screened with 1 milli-
meter of silver may be used in periods of one hour each, several times a
week, until an exposure of ten hours has been given. A better method
(•(insists in the use of two hundred millicuries for five hours. Barringer

212 RADIUM THERAPY

has applied in some eases unscreened emanation to the surface of
bladder growths via the urethra. The largest dose used by this author
was 500 to 1000 millicuries for 650 millicurie hours. In some cases, 50
millicuries contained in a steel needle was inserted into the growth for
100 millicurie hours. In other cases, bare emanation ampoules were bur-
ied in the growth.

Application through a Suprapubic Cystotomy Wound. — When accu-
rate application through the urethra, for any reason, is impossible, supra-
pubic cystotomy may be performed in order to render the growth acces-
sible. Radium tubes may then be introduced through the cystotomy
wound and held in position by sutures or by a long pliable silver wire
which may be bent to the proper angle and fastened to the abdomen by
adhesive strips. Using this technic from 100 to 200 millicuries screened
with 2 millimeters of brass and 10 millimeters of rubber may be applied to
the growth for from ten to twenty hours in periods of five to ten hours each.
In some cases, radium emanation may be inserted into the growth. Five to
eight steel needles having a wall thickness of 0.4 mm. and containing 60 to
90 millicuries may be inserted for twelve or eight hours. In other cases
bare emanation ampoules may be buried in the growth. In addition to the
intravesical treatment, heavily screened radium may be applied to the
perineum or inserted into the vagina or rectum in order to cross fire the
growth. Care must be taken not to overexpose either of these cavities.
In the treatment of carcinoma of the bladder it should be remembered
that growths that are superficial may sometimes be successfully treated
via the iirethral canal. For larger and deeply infiltrating growths, how-
ever, the use of large quantities of heavily screened radium at a certain dis-
tance from the tumor is imperative. Such cases usually demand that the
bladder be opened suprapubically in order to render the tumor accessible.
In still other cases, in which the age of the patient or other factors render it
inadvisable to open the bladder, palliative treatment may be carried out
from the skin surfaces by using large quantities of radium (500 to 1000 or
more me.) heavily screened at a distance of 10 centimeters from the skin.

One of our cases of inoperable carcinoma of the bladder, treated intra-
vesically, which was referred by Dr. M. L. Harris, has been well for more
than five years.

(15) Carcinoma of the Breast

Operable Cases. — The policy of declining to treat operable cases of
this disease solely with radium should be followed. Preoperative radia-
tion of the breast and its lymphatics followed by operation seems the
most logical procedure. Postoperative radiation of the operative field
and the areas most likely to harbor metastatie deposits should be carried
out. When at least 500 milligrams of radium are available, the thorough
saturation of the whole chest wall and its draining lymphatics with deep
penetrating rays is advisable. There are certain operable cases in which

RADIUM IN GENERAL SURGERY

213

•-•" O » ".••'••,.•.'•• "•*• •'••. '•'.

;-<«S^N';- ' K~:-v
*'''

C": '"•••:. ** f] -'•••'

. -• . ., .;->x-- . . _ .;;.--! •:.,.. '

Fig. 76. — Carcinoma of the breast after powerful radiation. The entire section is shown.
Slightly 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 of the rays than the normal
glands, and yet the former exhihit 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 hypertrophied cells. B, Normal glandular elements. C, Can-
cerous islets in the process of degeneration. D, Connective tissue stroma of neoplasm. D', Meta-
plastic connective tissue, uniting and taking the place of destroyed parenchyma.

214

RADIUM 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. 77. — Portion of Fig. 76 at B. Knlargecl 800 diameters.

A, Normal glandular cell. B, Supporting tissue. C, Lumen of excretory duct. D, Kpithclial
tell bordering upon an excretory duct.

Fig. 78. — Portion of Fig. 76 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, Hypertrophied nucleus. B, Cell with pycnotic nucleus. CC ', Atrophied cell with nucleus
absent (Karyolysis). D, Young fibroblast penetrating into a degenerated neoplastic islet.

Inoperable Cases. — In cases inoperable on account of the extent of the
disease, only palliative treatment as 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 not

RADIUM IN GENERAL SURGERY

215

only the whole breast but 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-

:'• '*'

^ " m Ft%&'

&;::>** ' .»:>kl-

. ... .v-^'SftV " -*ii

. v ^%iti^

Fig. 79. — Atypic cubical epithelioma of the breast, before radiation. Slightly enlarged (97

diameters).

A, Center of an epitheliomatous lobule. BB, Dense connective tissue forming the stroma.
C, Excretory duct of the mammary gland. D, Group of glandular elements.

idly growing type of carcinoma, response to radium treatment is likely
to be poor, although pain may be relieved.

216

RADIUM THERAPY

Technic of Treatment of Carcinoma of the Breast. — Small cutaneous
nodules or superficial ulcerations occurring on the chest wall may fre-
quently be healed by surface radiation. The technic is the same as that
for primary epithelioma of grave type involving the skin. Deeper nod-
ules attached to the bone or cartilage of the chest wall may be treated
effectively by surface applications or by the insertion into the nodule of
a platinum emanation needle containing twenty-five millicuries for eight-
een hours. (Hay ward Pinch.) In other cases, bare emanation ampoules
may be inserted.

it
, &
1 N-

.ti

, *

1 -

ffiS

-(^

V.JJV

• ' I ' « • ^

' »S

Fig. 80. — A part of Fig. 79. Highly magnified (800 diameters). A, Cubic epitheliomatous
cell of moderate size, with a single round nucleus am! homogeneous protoplasm. Note the ab-
sence of connective tissue and the intracellular pseudoparasitic elements in the whole of this
preparation which is taken from the center of a lobule. All these cells resemble one another.

When large and deep tumor masses are present, radiations should be
of a penetrating character. In some cases, 400 millicuries, screened with
2 millimeters of brass and evenly disposed on a pad 9 x 12 cm., may be
placed at a distance of 6 centimeters. A total exposure of thirty hours
in periods of ten or more hours each may be given.

In other cases demanding deep effects, 600 millicuries, screened with
2 millimeters of brass may be placed at a distance of 10 centimeters and

RADIUM IN GENERAL SURGERY

217

an exposure of thirty hours in periods of ten or more hours each may be
given. Sometimes when pleural or peritoneal effusion has supervened in
consequence of the involvement of the pleura or peritoneum by the
growth, the fluid may be withdrawn and deep radiation immediately
given. In some cases, the effusion has not reappeared.

Douglas Quick has recently reported upon the method of burying bare
emanation ampoules in the tiimor in cases of inoperable breast carci-

• * t

:. %••;• . . • .:•/

,.••;•.-•%• .

f v.

r ... .. ' •?•'•'

L- .•.-.;•.

• . - . »•**._ .

• .

B
A

••

•

, :

-,: •

Fig. 81. — Same epithelioma as in Fig. 79, after radiation. Slightly enlarged (97 diameters).
Section removed from tissue situated at depth of 2 cm. 16 days after radiation. The elements of
the parenchyma are no longer grouped, as in Fig. 79, in lobular masses. These have become in-
vaded and dislocated hy young, connective tissue stroma. The epitheliomatous cells are degenerated
and swollen — zones of cytolysis. The connective tissue stroma is renewed and is very rich in
embryonic elements.

AA, Epitheliomatous cells hypcrtrophied and degenerated. BB, Young connective tissue rich
in new cells replacing the tumor elements, which have disappeared. C, Dense connective tissue, un-
disturbed, forming the bed of the primary neoplasm. Dt Clear zone of cytolysis.

218

RADIUM THERAPY

noma coincidently 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 in the statistics, although the initial
response to the treatment was favorable. Russell 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 polymorphism
of the tumor elements, their hypertrophic and malformed nuclear structures. The epitheliomatous
nodules are infiltrated with a vascular connective tissue development in a state of paraembryonic
metaplasia. Notice the presence, interspersed amongst the epitheliomatous cells, of large, star-
shaped anastomosing connective tissue cells.

A, Hypertrophied epitheliomatous cell with a giant nucleus. A'A', Cells with multiple nuclei.
B, Capillaries, newly formed al the edge of the infiltration. CC, Pseudoparasitic Iwdies. DD',
Pycnotic nuclei. E, Star-shaped connective tissue cell joined to its neighbors by protoplasmic elonga-
tions. ^F, Young fibroblasts from the infiltration tissue. G, Monomiclear leucocytes interspci>rd
in the infiltration tissue. /•/. Cell with vacuoles without nucleus in state of cytolysis. //', Cell de-
prived of its nucleus (karyolysis).

radium salts into breast carcinomata combined with 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 were 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 writer treated 90 cases

Fig. 83. — Carcinoma of left breast. This tumor measured 16x12 cm., and was elevated about
5 cm. above the level of the skin. Photograph taken October, 1919. Patient referred by Dr. A. J.
Auner.

of breast carcinoma of different types. Eighty-five of these cases were
primarily inoperable or inoperable recurrences. Five cases were treated
that were operable so far as the disease was concerned, but inoperable

220

RADIUM THERAI'Y

on account of other conditions. In 30 of the 85 inoperable cases just
referred to, palliation only w;is 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

RADIUM IN GENERAL SURGERY 221

that we obtained was mentioned by the writer in a previous article (Illi-
nois Medical Journal, August, 1916). The patient referred to in the
above report died later, probably from spinal metastasis, but her condi-
tion was rendered comfortable and her life was apparently prolonged for
about four years.

Of the 5 operable cases that I have treated, 3 made a complete clinical
regression that has been maintained for periods of from six months to
two years. One case was refractory and one case abandoned treatment,
after an initial marked improvement was noted in both instances.

Improvement in the technic, such as the use of more massive doses of
radium at a considerable distance from the skin combined with the
implantation of bare emanation ampoules has led to better success
in the last few years than was formerly thought possible.

(16) Carcinoma of the Cervix Uteri

Operable Cases. — In the treatment of operable cases of cancer of the
cervix, it was the general opinion until recently that hysterectomy with
preoperative and postoperative radiations was the method of choice.
Janeway and others have lately expressed the opinion that radium treat-
ment alone, in certain cases of operable cancer of the cervix, is now
justified. Some authors even state that operation in cancer of the cervix
should be replaced by radium. We have already referred to the fact that
Bumm, Doederlein and Kroenig have taken this position and have aban-
doned operation in favor of radium treatment in all cases of cervical
cancer. Schaefer, a coworker of Bumm, has reported the following
results: Of 155 cases of cancer of the uterus treated with radium which
were either operable or on the borderline of operability, recovery oc-
curred in 83 (53.54 per cent). Seventy-four of these cases were operable.
Of these, 48. (66. 21 per cent) were well after periods of one to three
years. The foregoing results may be compared with the results of opera-
tion in 203 cases reported by the same author. In this series 98 (48.27
per cent) were well after periods of one to three years. Radiation seemed
therefore to give results better than those obtained by operation. On the
basis of these results, Schaefer has also abandoned operation for radia-
tion in cervical cancer.

Borderline Cases. — In cases in which the surgeon is in doubt as to the
advisability of operation, radium treatment is undoubtedly the prefer-
able procedure. In these cases, long experience has shown that operative
interference is not followed by good results. In some cases in this cate-
gory and even in some cases that are strictly inoperable, radium treatment
may render the case operable. It is probably best, however, not to at-
tempt to remove the uterus when a clinical recovery has occurred under
radium.

222

RADIUM THERAPY

Fig. 85. — Metatypic pavement cell epithelioma of the neck of the uterus, liefore treatment. ( Kn-

larged 180 diameters.)

C--

Fig. 86. — Same epithelioma as in Fig. 85. Fragment removed 10 days after the first application of

radium. (Enlarged 380 diameters.)

A, 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 budded, nuclei.

RADIUM IN GENERAL SURGERY

223

Inoperable Cases. — "Uterine cancer continues to yield most gratifying
results and the effect of radium treatment in inoperable cases is far in
advance of those obtained by any other known medical or surgical meth-
ods." (Report of the London Radium Institute.) Certain authors are of
the opinion that 25 per cent of inoperable uterine and vaginal cancer can
be cured by radium.

The clinical improvement of the majority of cases of carcinoma of the
cervix under radium is striking. Cessation of the hemorrhage and foul
discharge and relief from pain are very frequently obtained. Disappear-
ance of fungating masses and healing of ulceration are often noted. In

- -C

Fig. 87. — Same epithelioma as in Fig. 85. Section removed on the 29tli day after the first radia-
tion. (Enlarged 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-
nuclear cells. C, Remains of necrotic cells intermingled with polynuclear cells which disorganize and
absorb them. U, Young connective tissue rich in embryonic cells, fibroblasts, plasma cells; the be-
ginning of a cicatrization occupies the larger portion of the preparation.

some cases, palliation only is to be expected. In a few cases, no improve-
ment is obtained.

The Technic of Treatment of Carcinoma of the Cervix. — The technic of
treatment naturally varies with different cases, and indeed almost every
experienced worker with radium has, to some extent, an individual
method. The difference in technic is quite remarkable 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 Avriters 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, Begrais, Janeway, Kelly and Burnam, Hayward Pinch, Schmitz,
Wickham and many others, seems to demonstrate clearly that moderate
dosage brings about the 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 that several

, V " ' " B
B /.

A -

- -B

-B

Fig. 88. — Same epithelioma as in Fig. 85. Fragment removed from the surface of the cicatrix
of the neck of the uterus three months after first radiation. Dense connective tissue, rich in cellu-
lar elements.

A, Well developed, star-shaped connective tissue cells. B, Newly formed capillaries.

treatments are often preferable to a single treatment, although the effect
may not seem quite so brilliant. Whether a certain amount of curetting
should precede radium treatment in order to remove fungating masses is
debatable. We believe it is not advisable. We are opposed to prelim-
inary cauterization undertaken for the same purpose. In the technic of
treatment much depends upon the distribution of the radium with refer-
ence to the growth. When the radium is not too concentrated per unit
area, larger doses are naturally tolerated.

We shall mention at this time the technic of only a few therapeutists.

Burrows (Manchester and District Radium Institute) gives an exposure

RADIUM IN GENERAL SURGERY 225

of 3000 millicurie hours. He buries in the growth 5 to 7 platinum tubes
(wall thickness %0 mm.) containing 120 millicuries and allows them to
remain twenty-four hours.

Hay ward Pinch (London Radium Institute) gives a total exposure of
about 1600 millicurie hours. One tube of not less than 53.6 me. is intro-
duced, if possible, into the cervical canal, and if this is impossible, into
the posterior vaginal fornix. The screening is 2 mm. of lead plus 2 mm.
of rubber. Several treatments are given — the duration of the entire
treatment being twenty-four to thirty hours.

Janeway advises in average cases an exposure of 6000 millicurie hours.
He used 300 millicuries in 3 tubes inside the uterus and 3 tubes contain-
ing 200 millicuries over the cervix. The screening is the equivalent of
3' millimeters of lead plus rubber. One treatment of twelve hours is
given. More recently he has inserted, in addition, bare emanation tubes
into the cervix.

Schmitz gives a total exposure of 2000 to 2400 milligram hours in
the cervix and later the same dose against the cervix. He uses fifty
milligrams screened with 1.2 mm. of brass.

My technic in average cases has consisted in giving an exposure of
about 3000 millicurie hours. In suitable cases, 200 millicuries screened
with 2 mm. of silver are introduced into the cervix for seven and
one-half hours. Two subsequent exposures of fifteen hours each with
50 millicuries screened with 2 mm. of silver plus 2 or more mm. of
rubber against the cervix are then given at intervals of three or
four days. It must be emphasized that there is no one technic adapted
to all cases and that equally good results may doubtless be obtained in
the same class of cases by different methods. In addition to the intra-
uterine and intravaginal exposures, it is imperative to use powerful deep
radiations over the abdomen and sacrosciatic notches. Three portals of
entry may be mapped out on the abdomen. Five hundred to 1000 millicuries
screened with 2 mm. of brass may be applied over each portal at a distance
of 6 or 10 centimeters for twenty-five or eighteen hours in periods of ten or
more hours each. The emanation may be arranged on a pad having a
superficial area of 100 square centimeters. The splenic area should be
carefully protected during the abdominal radiations.

In carrying out intravaginal treatment, it is important to pack off well
the posterior vaginal wall, as the rectum is especially sensitive to radium
rays. Treatment may otherwise be followed by proctitis.

When treatment is undertaken for -recurrences after extensive pelvic
operations, the quantity of radium used in the vagina should be reduced
by one-half and the time of exposure by one-fourth, otherwise the radium
may cause at times a destructive and intractable reaction. Following
in) r;i vaginal radium treatment, douches should be systematically given
for at least six or eight weeks to prevent the formation of adhesions. A

226 RADIUM THERAPY

second series of treatments six or eight weeks after the first series may
be advisable but these should always be of less intensity. Too powerful
or too frequently repeated exposures may result in painful and destruc-
tive reactions which may appear many months after the treatment is
discontinued.

From the standpoint of treatment, Dr. John (1. Clark draws a sharp
distinction between cancer of the cervix and cancer of the fundus uteri.
In the former condition, he advises the use of radium ; in the latter, he
advocates hysterectomy even though the disease is advanced. Many
authors advise the use of radium in all borderline and advanced cases
of cancer of the uterus, irrespective of its location.

Results of the Radium Treatment of Uterine Cancer. — The literature
of the subject has grown to such great proportions that we shall mention
the results of only a few authors. Many additional references will be
found in the bibliography.

In the course of five years, IT. ('heron and Rubens-Duval treated 158
cases of primary and recurrent inoperable uterine and vaginal caneer.
In 155 cases there was improvement that was anatomically verified. In
93 cases, the improvement was marked. The authors state that in 46
cases there was probably a definite cure. In only 2 cases was the treat-
ment without appreciable good effect.

These authors have also reported a case that may be mentioned as show-
ing the possibility of a complete anatomical cure of localized cancer with
radium. The patient referred to suffered from inoperable cancer of the
uterus and made an apparent recovery under radium. Fifteen months
later the patient died of another disease and histological examinations of
the various organs of the body showed no trace of cancer.

Kelly and Burnani have reported a series of 213 cases of cancer of the
uterus treated witli radium in which the results are thus summarized by
the authors: "Out of 213 cases treated, 14 were operable and 199
inoperable.

"Operable cases: Of the 14 operable cases, 10 patients were operated
on and treated prophylactically with radium. Of these, 2 have been well
for more than three years, 1 for more than two years, 4 for more than
one year, and 3 for more than six months. The number is too small from
which to draw conclusions, and yet is suggestive when we consider that
in 75 per cent of all cases with operation there is recurrence and that
60 per cent of these recurrences take place within one year following
the operation.

"In four cases of the operable group, on account of some general con-
traindication to operation, radium alone was used. All of this group are
living and well ; two for over three years and two for over one year.

"Inoperable cases: The total number of inoperable eases and inoper-
able recurrent cases is 199, of which 53 patients have been clinically
cured, 109 markedly improved and 37 not improved.

RADIUM IN GENERAL SURGERY 227

"Our series includes 35 of originally inoperable cancer of the cervix
uteri or vagina in which 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. It also includes 18 cases of
originally inoperable recurrent cancers in which 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 for over six months. Excluding the operable cases, in which we
have 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 year limit,
which has been conventionally adopted by surgeons 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 ovor two years, 29 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 were 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.

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 cases forming the second group, reports
have been obtained from 45. Twenty-eight of these are living and 17
are dead. Twelve of the living cases are well after more than three
years. It may be stated, however, that in this group of inoperable cases
there were 12 in whom palliation alone was attempted.

Of the 40 inoperable recurrences forming the third group, we have
reports from 20. Of these 8 are living and 12 are dead.

Of a total of 138 doubtfully or wholly inoperable cases, 51 have been
lost sight of. Eighty-seven have been traced, of whom 30 are living
and 57 are dead. If we assume that none of the untraced cases is liv-
ing the proportion of clinical recoveries for more than three years is
slightly more than 21 per cent.

In the majority of all of our cases, except those in which palliation only
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 lymph 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 fiiled with hyaloplasm, with no elaboration of the collagen.

A, Fusiform cell. B, Vessel lying in sarcomatous tissue and bordered by tumor elements. Ct
Cells in atypic karyokinesis. D.E., Tlasma 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. Stuhr, which was
probably of the type just mentioned, a large mass was present in the
right hypoehondrium. The tumor extended from the costal arch to the
umbilicus and was apparently larger than a child's head. This growth
had been preceded a year before by a sarcoma of the right testis which
had been surgically removed. Complete disappearance of the abdominal

RADIUM IN GENERAL SURGERY

229

tumor occurred within a few weeks under radium treatment. The patient
is now in excellent health after more than three years.

Melanosarcoma is not, as a rule, favorably affected by radium but in
exceptional cases may yield completely.

We may refer briefly to sarcomata occurring in different situations.

(1) Sarcoma of the skin is usually amenable to radium treatment.

Fig. 90. — Same sarcoma as in pig. 89. Section of large nodule removed 15 days after powerful
irradiations. Slightly enlarged (80 diameters).

Zone A, Superficial part, in contact with the apparatus; zone of massive necrosis.

Zone B, Showing cellular monstrosities and phagocytes. Sarcomatous elements scanty but
quite bulky and in state of degeneration. Numerous leucocytes.

Zone C, Showing stratum of least modifications — nevertheless the sarcoma is modified. Hyper-
trophied forms of cells of monstrous shapes.

a. Monstrous degenerated cells, bb. Elongated sarcomatous elements having a resemblance to
young fibrohlasts. cc, Multinuclcated plasma cells. /, Sarcomatous vessels.

230 RADIUM THERAPY

(2) Periosteal sarcoma is frequently benefited by radium.

(3) Sarcomata of the tonsil and post nasal space are frequently amen-
able to radium and very striking results arc sometimes obtained. I have
treated in conjunction with Dr. (.). T. Freer three cases of sarcoma of the
postnasal space in which recovery occurred. Two of these cases 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.

v » •

Fig. 91. — Same sarcoma as in Fig. 89. After railiation. Highly magnified (400 diameters).

This section shows a portion of zone II in Fig. 90 and illustrates tin- extraordinary volume, and
the strange forms of the sarcoma elements under the influence <>f the radiation before they dis-
appear by phagocytosis. The relative scarcity of neoplastic cells is plainly discernible.

AA, Greatly hypertrophied sarcomatous cells with multiple or polylobular nuclei, with proto-
plasm, acidophilous, invaded by polynuclear leucocytes. BB, Neutrophilc polymiclear leucocytes
enclosed in the protoplasm 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 mediastiiial tumor
have received great benefit from radium treatment. It is probable that
many mediastiiial growths are lymphosarcornata and the excellent results
sometimes noted after radium .treatment. may be explained by this Fact.
Burnam has reported an interesting group of 8 cases oF mediastiiial

KADIUM IN GENERAL SURGERY

231

232

RADIUM THERAPY

tumor treated with radium, in which the greatest improvement occurred
in all but 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 me, 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

Fig. 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 iiares for six hours in sev-
eral periods of two or three 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, %o mm. screen, 8
hours), or bare emanation tubes may preferably be used. In orbital
sarcoma, 100 me., screened with 2 mm. of brass may be inserted into the
orbital cavity for six hours. This treatment should follow evisceration

RADIUM IN GENERAL SURGERY

233

or exenteration either at the time of the operation or in the event of
recurrence. In all types of deep sarcoma or when large masses exist,
deep raying with large quantities of radium is the method to be chosen.
Five hundred or 1000 inc., 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 me. hours and at a distance of

Fig. 95. — Patient in Fig. 94 after radium treatment. Photograph taken Oct. 20, 1921. Metas-
tases to the skin of the right hreast, abdomen and thighs occurred later. These disappeared under
radium. In December, 1921, patient appeared clinically well. In February, 1922, we learned
that patient's health was failing.

10 cm., 18,000 me. hours may be given. In mediastinal tumors, Kelly
and Burnam have used more than a gram of radium at a distance of
from 1% to 6 inches, for periods of four or more hours on each area.

Pancoast has reported some encouraging results following the radium
t refitment of brain tumors (sarcoma, glioma, endothelioma, pituitary
tumors).

234

KADI I'M TllICKAPY

big. 96: — Tumors -of' eyelids.' Mii-n>sc<>|iH- xrtiun Allowed lymplioma (?). Photograph taken July,
1920. I'atitMit referred by Dr. Wm. A. Fisher.

RADIUM IN GENERAL SURGERY

235

Fig. 97. — Patient in Kip:. 90 after radium treatment. Photograph taken September, 1920.
Patient was well one and one-half years later.

236

RADIUM THERAPY

Fig. 98. — Sarcoma of bone. Recurrence after operation. Patient referred by Dr. A. B. Kanavel.

RADIUM IN GENERAL SURGERY

237

Fig. 99. — Patient in Fig. 98 after radium treatment. Improvement was only temporary.

238

RADIUM THERAPY

Fig. 100. — Lymphosarcoma of neck. Photograph taken July, 1919. Note scar of previous operation.

RADIUM IN GENERAL SURGERY

239

....

fig. 101. — Patient in Fig. 100 after radium treatment. Photograph taken in December, 1919.
Later recurrences took place in throat, axillae, inguinal regions and abdomen which yielded for a
time to further treatment. The patient had about a year of comfort as the result of the treatment.

240 RADIUM THERAPY

B. BENIGN TUMORS

The treatment of keloids, nevi, etc., will he considered in the chapter
devoted to Radium in Dermatology.

The treatment of fihromyomata of the uterus will be considered in the
chapter on Radium in Gynecology.

C. CHRONIC INFECTIONS
Tuberculosis

Tuberculosis of the skin will be considered under Radium in Derma-
tology.

Tuberculous Adenitis

In the early stages of tuberculosis of the lymphatic glands, 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
]% me. 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 were clinically cured and two 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 considered in the chapter on Radium in General Surgery.

B. BENIGN TUMORS
Fibromyoma of the Uterus

Dr. Robert Abbe, of New York, was the pioneer in the use of radium
in fibromyoma of the uterus. His first case was treated in 1905 by 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,
Degrais, 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. lie ordinarily limits the use of
radium therefore to cases occurring within the menopausal cycle. Kelly
apparently docs not recognize an age limitation. Sixty-four of his cases
were under 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 when 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 carcinoma of the fundus. Many
authors do not regard the size of the tumor in itself as a contraindication
to radium. The cervical, the submucous 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 treatment is uterine hemor-

241

242 RADIUM THERAPY

rhage 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 but 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

RADIUM IN GYNECOLOGY 243

given by this author, the shorter exposure being used in women under
thirty-five and the longer, in women in the menopausal cycle.

Hayward 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 was repeated in six to eight
weeks. If the interior of the uterus was treated, an exposure of from
twenty-four to thirty hours Avas 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 millicnries, 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 curable 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" with bleeding, radium has 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
bleeding 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
RADIUM IN DERMATOLOGY

We have already referred to the fact that radium rays may produce
either a "selective" or an "inflammatory" reaction in the skin. By
some writers, 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 snow
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 favorable 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
persists. 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 granulomatous 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 lias
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 cliil-

Fig. 102. — Cicatricial keloid, following a burn of the face. Before radiation. Slightly en-
larged. The connective tissue cells are scanty and the elastic fibers 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

dren, a very excellent result is frequently obtained. In some cases the
skin may be quite normal in appearance after involution of the keloid.
In other cases, the treated area may be too white or too red, or it may
have a smooth, glazed 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 with
other methods of treatment, radium is easily the method of choice in
the treatment of this condition.

. j^l^ay** •^SxS^^T^.'^v- - •*f*c**f3fr'*3^*3y"£gf$3tiig££*zt*3'gll^

' <Cv^<> *T- "*j» "C*~ ***--~*&^3*

••-• ««•„•»» ,« .,,, •

"S- --""rf*1*. • "•* **•*•* V ^ * • *^~* *^" - •

- -" ~' " "-. — •* -"*'

Fig. 103. — Same keloid as in Fig. 102 after radiation. Highly magnified. Greater development
of the connective tissue cells; polymorphism of these cells; notable increase of elastic fibers.

//, Epidermis directly above corium in a state of transformation. B, Surface zone of the
keloid transformed into young fibroma, rich in cells. C, Young fibroblasts forming a zone resem-
bling a myomatous development. D, Deeper zone which has 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 patient 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 Yi0 mm. of lead and applied
closely to the skin, a course of two to four hours in six periods may be

248

RADir.M TIIKU.U'Y

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 millicuries of radium

Fig. 104. — Keloid of right great toe. Photograph taken May, 1914. Patient referred by Dr. J. R.

Buchbinder.

l;ig. 105. — Patient in Fig. 104 after radium treatment. Photograph taken Jamuiry, 1915.

emanation having a concentration of 5 millicuries 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 about six weeks, but the sub-
sequent course should be of less intensity.

RADIUM IN DERMATOLOGY 249

"Above all, the principle which governs the technie, and of which the
operator must never lose sight, is the necessity for influencing the
keloids to the extreme depth of their base, and acting on their peripheral
prolongation's, which sometimes extend far beyond their visible limits.
The treatment of a keloid should only be considered complete when the
tissues show an almost normal elasticity on palpation, even at a depth.

"It is possible then, to make use of total radiations of great power,
composed largely of Beta rays, and employ them in frequently repeated
exposures of short duration; or of 'surpenetrant' radiations of weak
quantitative value, allowing them a sufficiently long action; or of the
simultaneous application of several instruments acting opposite each
other, by the system of 'cross fire.' By these means, which lead to the
absorption of the growths, we can utilize the selective power of radium.
But they are sometimes slow, and in order to gain time it is often well
to act more energetically, undeterred by the fear of producing a certain
degree of destructive inflammation. In the application of these different
processes, two important data must be borne in mind, viz., (1) the great
resistance shown by keloidal tissue, from which results the possibility of
using fairly large doses, without producing any reaction worth mention-
ing; (2) the futility of aiming at the entire avoidance of superficial inflam-
mation. If the 'specific' dose be slightly exceeded, a small dry crust
with a dry base is produced which will not in any way hinder the course
of the treatment. If there is any hesitation as to which of two doses,
intended to obtain simple modification without destruction, shall be
chosen, there can, therefore, be no objection to deciding on the stronger.
Keloids which respond most readily to the employment of specific doses
are those of recent formation in process of evolution, and those of young
children." ("NVickham and Degrais.)

In the treatment of keloids mixed with scar tissue and also in dealing
with fibroselerotic bands, the doses suggested above may be slightly in-
creased so as to cause an actual destructive reaction. This procedure
should be followed, however, only when the milder doses have failed.
It must be remembered also that destructive doses may cause a reaction
requiring weeks for healing and that telangiectasia may eventually occur.
Even under these circumstances the final result, skillfully produced, is
usually much to be preferred to the original lesion. As pointed out by
Wickham and Degrais not all disfiguring scars are amenable to radium
treatment. Depressed scars, e.g., such as those resulting from smallpox,
cannot be remedied by radium.

250

RADIUM T11KRAPY

Fig. 106. — Keloid of back due to burn from a flat-iron. The tumor was situated between the spine
and lower angle of right scapula. Photograph taken April, 1914.

RADIUM IN DERMATOLOGY

251

Fig. 107. — Patient in Fig. 106 after radium treatment. Photograph taken September, 1914.
Only the lower portion of the keloid had been treated when the photograph was taken. Later the
rest of the tumor was removed with radium.

252

RADIUM THERAPY

1'ig. 108. — Keloid of back of neck. Recurrence after surgical removal. 1'atient referred by Dr.

Uayard Holmes.

RADIUM IN DERMATOLOGY

253

Fig. 109. — Patient in Fig. 108 after radium treatment.

254

RADIUM THERAPY

Fig. 110. — "Acne keloid" of back of neck.

RADIUM IN DERMATOLOGY

255

Fig. Ill . — Patient in Fig. 110 after radium treatment.

256

RADIUM THERAPY

Fig. 112. — Keloid of face following a htirn. Patient referred by Dr. T. R. Ilinchion. Photograph

taken January, 1919.

RADIUM IN DERMATOLOGY

257

Fig. 113. — Patient in Fig. 112 after radium treatment. Photograph taken June, 1920.

258

RADIUM THERAPY

(b) Angiomata and Lymphangiomata

Angiomata 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 boiling water or hydrogen peroxide, desl motion
by liquid air, C02 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,

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-

RADIUM IN DERMATOLOGY

259

ical standpoint, we may follow, in the main, the grouping suggested by
Wickham and Degrais. On the basis of treatment, these authors have
divided vascular nevi into the following groups :

1. Flat, superficial angiomata, level with the skin.

2. Flat, deeply infiltrating angiomata, level with the skin.

Fig. 115. — Same angioma as in Fig. 114, after treatment with radium by tiie method of
"selective reaction," i.e., without visible macroscopic inflammation. Slightly enlarged (120 di-
ameters). The epidermis is of normal thickness and freed from interpapillary encroachments. The
derma is composed of connective tissue rich in. cells of mature fibroblast 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, Epidermis resting on basal tissue which is hardly recognizable. H, 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.

face.

Raised angiomata, usually with hard and more or less sclerotic sur-

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

.« o

re o

2G2

RADIUM THERAPY

Fig. 120. — Cavernous angioma of lower lip. Patient referred by Dr. S. I,. Fridus.

KAD1UM IN DERMATOLOGY

2G3

Fig. 121. — Patient in Fig. 120 after radium treatment.

264

RADIUM THKRAPY

Fig. 122. — Flat angioma of side of face, neck, chin and lower lip.

RADIUM IN DERMATOLOGY

265

Fig. 123. --Patient in Via. 1-- after radium treatment. Tlic result in this case was better than in-
dicated by the photograph. The angioma was removed by "selective reaction."

2(56

KAIUUM THERAPY

RADIUM IN DERMATOLOGY

267

268

KADIUM THERAPY

Fig. 128. — Slightly elevated angioma of side of face. Lesion was of dark. ]iurpli>li-ri'il colur. I'a-
tient referred by Dr. H. Kdward Sauer.

RADIUM IN DERMATOLOGY

269

' Fig. 129.— Patient in Fig. 128 after radium treatment. The result in this case is not^ as pood
as indicated in the photograph as a few tclangifc use:-, have appeared in the last year. Tin s< arc
easily concealed, however.

270

RADIUM THERAPY

Fig. 130. — Angiosarcoma (?) of left arm; note tumor of arm and fiat angioma of back of arm.

Photograph taken April, 1916.

RADIUM IN DERMATOLOGY

271

Fig. 131. — Patient in Fig. 130 after radium treatment. Note the disappearance of tumor
and normal outline of arm. Method o£ dressing with strips of rubber tissue. A superficial derma-
titis is also shown. Photograph taken June, 1916. Patient was well five years later.

272

RADIUM THERAPY

= 3
o

•as

RADIUM IN DERMATOLOGY 273

different types, however, merge into each other and different forms may
be present in the same person.

The Technic of Treatment of An°'iomata. — The method of treatment
\vith radium naturally varies with the type. For most superficial angio-
mata, nothing equals the "toiles" or the glazed plaques. For deep
angiomatous tumors, tubes may be employed, although the flat appli-
cators answer equally as well.

1. Flat Superficial Angiomata ("Port-wine Stains"). — In the treatment
of this type of tumor, one cannot too strongly insist upon the necessity
of the avoidance of inflammatory reaction. The production of slight
redness and scaling of the skin is sometimes permissible, but an endeavor to
bring about more rapid results by strong treatment will only be fraught
with disaster. If the dosage is too powerful or the technic unskillful, the
coloring may not be uniform and telangiectasia may occur. As an ex-
ample of the technic, we may suggest the use of a ]/(>o strength "toile."
With this style of applicator screened with 1/iiio or vfio mm. of 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, Deep1.// Infiltrating Angiomata. — Th? method of treatment of
this type of angiomu is similar to that employed in the first group, except
that it is permissible to use stronger dos-o.s. 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-
what more boldly. With 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 hours may be given. Only a few
square centimeters should be treated at one time until the effect is ob-
served. Severe reactions should be avoided. In subsequent courses of treat-
ment, instituted after six weeks or two months have elapsed, the screening
may be increased to -/K, 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 goo'd results in this group, but in some cases the final appearance
is excellent.

274 RADIUM THERAPY

3. Rained "Hard", Angiomata. — This 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. With % strength applicators, applied
closely to the skin, a total exposure of two hours when unscreened,
or five hours when screened with Vio mm. of lend may be given as a first
course. Screened with Vio nun. of lead plus 2 mm. of rubber, ten hours
may lie given. Not over 4 square cm. should be treated ill one time. The
treatment should be divided into several periods of one hour e;ieh. AY lieu
the rend ion subsides, a less intensive course with double Hie thickness of
screen may be given.

4. Raited, "Soft" Aii</ioni<ilii. — Tn this group are included variously
si/.ed tumors. A frequent lype is the "cavernous angioma," seen partic-
ularly in infants. This tumor is elevated one or more centimeters above
I lie 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 effects. 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
fh-e" 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
may be given. As in the previous instances, not over 4 square cm. 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, RubcutdHfous and Snbnnicous Tumor*. — Very extensive tumors
may be treated successfully. Tn these eases 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
millicuries of radium emanation, having a concentration of 5 millicuries
per square centimeter, screened with 2 millimeters of brass and placed at
a distance of two 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-strength radium plaques 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, although two, or at most three, courses are

RADIUM IN DERMATOLOGY

275

276

RADIUM THERAPY

Fig. 136. — Pigmented nevus of left lower eyelid and face.

RADIUM IN DERMATOLOGY

277

Fig. 137. — I'atient in Fig. 136 after radium treatment.

278

RADIUM THERAPY

KADHJM IN IIKUMATOLOGY

270

280

THERAPY

usually sufficient. Oftentimes, large angiomatous tumoi's 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. — Tuberculosis verrucosa cutis of first phalanx of left middle finger.

Fig. 143. — Patient in Fig. 142 after radium treatment.

radium more than three hundred angiomata of various types. In some
cases, the results have been excellent. In a few cases, there has been
no noteworthy improvement.

RADIUM IN DKRMATOLOGY

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
case involving the buttock and thigh that had been successfully treated.
In lymphangiomata affecting the mucous membranes and particularly

Fig. 144. -Tnlu -rcnlusis \ernicosa cutis of first phalanx of li-ft thumb.

FiK- 145. — Patient in I'ig. 144 after radium treatment.

the tongue, radium is of unique value and can hardly be replaced by any
other agent. The method of treatment is similar to that for angiomata
of the third group.

Pigmcnted nevi involving an area of several square centimeters are
amenable to radium. Very minute nevi should be treated by other meth-

'JS2

RADIUM TIIKUAI'Y

ods. Growths that are very unsightly in consequence of rugosities and
great thickening. Hie presence of hair, and very dark pigment, are espe-
cially likely to yield to treatment. Radium lias unfortunately no selec-
tive action on pigmented nevi and in order to cause them to disappear
destructive doses must lie iised. The final result therefore may not be
as good as in angiomata, due to the fact that the treated area may lie

Fig. 14fi. — Lupus vulgaris of right check in girl aged 13.

unevenly colored and there may be points of repigmentation. We do
not therefore recommend the use of radium 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-
quarter strength applicators, applied closely, an exposure of one or two
hours may be given without screening. Following this, an exposure of
two hours with a screen of %0 millimeter of lead may be given. This

RADIUM IN DERMATOLOGY

283

procedure produces a slightly destructive action. The treatment may
be repeated, but with less intensity, in eight weeks. The final result will
depend very largely upon the judicious selection of cases and perhaps
most of all, as in other cosmetic difficulties, upon the skill and care with
which the treatment is carried out.

"Fordyce's disease" of the mucous membrane of the cheek and lips

Fig. 147. — raticnt in Fig. 146 after radium treatment.

lias been treated successfully by Hayward Pinch, myself and other writ-
ers. A glazed plaque of % strength, unscreened, may be used and a sharp
reaction may be produced. An exposure of forty-five to sixty minutes
may be given and repeated, if necessary, in a few weeks.

In various other benign tumors of the skin, radium has been found to be
of value. Among these may be mentioned especially linear nevus, in which
radium is of the greatest value. Dermatitis papillaris capillitii, molluscum

284

RADIUM THERAPY

Kig. 1-48. — Lupus vulgaris of right cheek.

contagiosum, multiple benign cystic epithelioma and some types of xan-
thoma are also susceptible to radium.

C. CHRONIC INFECTIONS

(a) Tuberculosis

In certain types of skin tuberculosis, radium is of value. Tuberculosis
verrucosa cutis frequently responds well. Destructive doses, such as may

RADIUM IN DERMATOLOGY

285

itf. 149. — Patient in Fig. 148 after radium treatment.

be obtained by using % strength applicators with a screen of ^Q mm. of
lead for five or six hours in several periods of one to two hours each, may
be used. In lupus vulgaris, radium is only of limited vise, being, in the
writer's judgment, distinctly inferior to the Pinsen light. In using radium,
the best plan of procedure consists in using % or % strength glazed appli-
cators with a yw mm. lead screen. A total exposure of six to twelve hours
may be given in divided doses. Only small lesions should ordinarily be

286

RADII' M THKRAPY

treated. Large lupus patches may even spread at the border and become
worse under radium treatment if insufficient doses or unskillful technie
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 lie employed.

(b) Blastomycosis

In 191.'!, the writer reported the results of the radium treatment of blas-
tomyeosis of the eyelid. Since that time, several other cases of blastomy-
cosis of the skin have been treated successfully. Radiation similar to that

Fig. 150. — Ulastoniycosis of left inner cantlins

Kit;. 151. — Patient in FIR. 1.^1 after railium
t reatment.

used for tuberculosis, but of less intensity is efficient. Degrais, Wickliam
and others have found local radium treatment of value in aiding resolu-
tion of syphilitic skin eruptions. The technie is similar to that described
above as suitable in tuberculosis.

Radium has been used successfully by Kahler, Guttman and others
in rhinoscleroma and by Ileverdald in aetinomvcosis.

1). INFLAMMATORY AND GRANULOMATOUS INFILTRATIONS OF

UNCERTAIN NATURE

In this group of dermatoses, radium is of considerable value. In
psoriasis, lichen planus, lichen chnmicus simplex, chronic eczema and

RADIUM IN DERMATOLOGY

287

Fig. 152. — Lupus erytlu-niatusus <>f nose and checks.

Fig. 153. — Patient in Fig. 152 after radium treatment. Photograph taken two months after

treatment.

288

KADI I'M THKRAl'Y

lupus erythematosus, radium treatment offers, in selected cases, 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
be used successfully. It must lie remembered, however, that neither
radium nor any other measure prevents recurrence of the patches. With

rythematosus involving nose and chetk^.

Fig. 154. — ly

% strength applicators, screened with %0 mm- of lead, an exposure of
one or two hours and often less, in several periods, is usually sufficient
to cause involution. Inflammatory- reaction should be avoided.

In lichen planus confined to small areas radium often relieves the
itching and hastens involution. In lichen planus of the mucous mem-
branes, radium is especially valuable. The technie of treatment is the
same as that suggested for psoriasis. Not more than % of the dose em-
ployed on the skin should be used on lesions of the mucous membranes.

RADIUM IN DERMATOLOGY

28!)

In lichen chronicus simplex, radium often gives the most striking
relief, the itching frequently disappearing very promptly. Short appli-
cations of ]/4 to % strength glazed applicators, unscreened, are advisable.
Two or three exposures, each lasting three minutes, and repeated at
intervals of a week, are efficient. Inflammatory reaction should be
avoided.

Certain cases of chronic eczema may yield to similar treatment.

The writer has treated more than 50 cases of lupus erythematosus

Fig. 155. — Patient in Fig. 154 after radium treatment.

with radium. In this curious and puzzling disease, radium is one of
our most valuable agents. Considerable judgment is necessary in treat-
ing this disorder, and caution should be practiced until the degree of
irritability of the individual case is made evident. Most cases require
only a moderate reaction to produce evolution. Treatment may be car-
ried out by employing % strength glazed applicators, screened with
Yin mm. of lead. One-half hour exposures may be given on successive
or alternate days until four or five treatments have been given.- The

290

RADIUM THERAPY

Fig. 156. — Lupus erytbematosus involving right cheek and upper lip.

RADIUM IN DERMATOLOGY

291

Fig. 157. — Patient in Fig. 156 after radium treatment.

292

RADIUM THERAPY

Fig. 158. — Lupus erythematosus of four years' duration.

RADIUM IN DKRMATOLOGY

293

Fig. 15y. — Patient in Fig. 158 after radium treat men t. Involuted areas show the scarring of the
disease and are of a lighter color than the normal skin.

294 RADIUM THERAPY

effect is noted and the treatment is repeated as soon as the reaction, which
may last for from two to four weeks, has subsided. Care must be taken
that the edge of the applicator overlaps for at least five to ten millimeters,
the visible edge of the disease. This treatment is usually adapted only to
the cases of "fixed type." Freedom from the disease for several years
may be experienced in 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 from the treatment. In leukemia cutis, radium
is of value and may cause resolution of the involved areas.

E. HYPERTROPHIES

In many of the disorders classed as hypertrophies, radium is of con-
siderable value. In clavus, 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 % strength apparatus, unscreened, for one-half to two hours, or
screened with ^Q 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
plantar 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 apparatus, screened with %<> mm- of lead, for four hours
in periods of one hour each. In certain rare disorders, such as acanthosis
nigricans and Darier's disease, radium treatment would undoubtedly
be of value insofar as the removal of localized areas of the disorder is
concerned. R. L. Sutton has used radium successfully in a "synovial
lesion" of the skin.

F. NEUROSES OF THE SKIN

We have already spoken of the relief obtained by the use of radium
in certain itching dermatoses, notably lichen chronicns simplex, lichen
planus, and eczema. There are other disorders classed as neuroses in
which the subjective symptoms are prominent, but in which little or
nothing is seen objectively except the lesions produced by scratching.
Localized pruritus, such as pruritus ani and pruritus vulvae, is fre-
quently relieved by radium. In these affections, the best method of
treatment is by means of unscreened glazed apparatus. Exposures of

RADIUM IN DERMATOLOGY 295

three to five minutes' duration repeated several times at intervals of
a week, may be given. The total amount of radiation should never be
sufficient to produce an inflammatory reaction. In various other affec-
tions, the analgesic action of radium has been made use of. In hyper-
esthesia, following herpes zoster, in neuritis and in intercostal and sci-
atic neuralgia, Wickham found radium of value. He used approximately
% strength apparatus screened with %o 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 rhinophyma
very good results have been obtained by Wickham and Degrais and oth-
ers. In these cases, % strength glazed applicators, screened with %o mm.
of lead, are usually employed and a slight reaction may be produced.
A total exposure of two or three hours in several periods will usually
be sufficient. Subsequent courses may be given at intervals of three to
six weeks. Oood results may follow the local treatment of acne varioli-
formis although, of course, no influence is exerted in preventing the for-
mation of new lesions. In hyperidrosis, radium is sometimes of value.
The glazed plaques are the most convenient form of apparatus. Inflam-
matory reaction should never be produced.

(b) Hair and Hair Follicles

In the extreme cases of hypertrichosis which 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 produce per-
manent alopecia 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 affected must be cov-
ered by at least 5 mm. of rubber covered lead. One hundred fifty me.,
screened with 2 mm. of brass, may be arranged on a wooden pad 6x8x2
cm. At a distance of 2 cm., which is the thickness of the wooden pad, an
exposure of thirty hours in two periods may be given. In cases in which
temporary alopecia is desired, as in ringworm and sycosis vulgaris, ra-
dium may be used instead of x-rays, though often inferior in convenience
to the latter agent. Radium is perhaps safer in inexpert hands. In
extensive ringworm of the scalp, we have used the following technic.
Blocks of soft wood or cork (2x2x1 cm.) may be arranged to form an
applicator having a superficial area of 100 square centimeters. Radium em-

296

RADIUM THERAPY

Fig. 160. — Sycosis vulgaris.

Fig. 161. — Patient in Fig. 160 after removal of hair with radium.

anation tubes may be arranged on this applicator in the ratio of 1.25 me.
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 periods of fifteen hours each. Temporary alopecia results.

CHAPTER XVIII

RADIUM IN OPHTHALMOLOGY, OTOLOGY, RHINOLOGY AND

LARYNGOLOGY

OPHTHALMOLOGY

A. Malignant Tumors

Epithelioma of the Eyelid has been referred to in the chapter on
Radium in Dermatology.

Epithelioma of the Conjunctiva has been successfully treated by Wick-
ham and Degrais and others.

Sarcoma of the Orbit has been considered in the chapter on Radium
in General Surgery.

B. Vernal Conjunctivitis

In vernal conjunctivitis radium is of considerable value. Sometimes
the most rebellious cases are completely relieved. Treatment should be
carried out cautiously. A "full strength" applicator unscreened may
be employed and a fifteen minute exposure given. In two weeks the
exposure may be repeated, but only if inflammatory reaction has been
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, Shiun-
way, and many others have reported successful results.

C. Trachoma

Radium is often of benefit in this intractable condition. The teclmic
is similar to that suggested for vernal conjunctivitis.

D. Cataract

Cohen and Levin have reported upon the use of radium in twenty-four
cases of immature cataract and claim improvement in 87.5 per cent of the
cases. Twenty to forty milligrams of radium element were used.
Gamma rays only were utilized. The radium was applied over the closed
eyelid at a distance of two centimeters for two hours.

W. S. Franklin and F. C. Corcles have apparently confirmed these results.
Those authors have treated thirty-one cases of immature cataract of
which 84.3 per cent showed a change for the better ranging from an
improvement of three to four letters on the test chart to a complete dis-
appearance of the process. They used the following teclmic. At a dis-

297

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 area of 50.26 square millimeters were utilized.

OTOLOGY

In granulomata and papillomata in the external auditory canal, radium
is frequently of great value. I have treated a number of cases in which
recovery has been brought about. Fifty inillicuries 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 improvement
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 been considered
under Radium in General Surgery. In chronic ethmoiditis with recur-
ring polypoid degeneration, radium has been used with good results by
0. T. Freer and T. Melville Hardie. A platinum tube having a wall thick-
ness of 0.3 mm. and containing 50 me. of radium emanation may be
inserted into the ethmoid sinus for 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
described below.

B. Benign Growths of the Larynx

1. Papilloma of the Larynx. — Abbe has reported a remarkable and suc-
cessful case of papilloma of the vocal cord in which complete relief was
obtained. The singing voice was restored and recovery has been main-
tained for more than ten years. In this patient a preliminary tracheot-
omy was performed and anesthesia was continued through the tracheot-
omy opening during the radium application. One hundred milligrams
of radium were applied, by means of a wire passed through the trache-
otomy wound into the mouth, for thirty minutes.

In a personal communication to the writer, Abbe states that other
similar cases have since been treated and have done equally wTell.

OPHTHALMOLOGY, OTOLOGY, AND LARYNGOLOGY 299

G. B. Nc\v, of the Mayo Clinic, states that "the treatment of multiple
papilloma of the larynx in children has been improved wonderfully by
the addition of radium.

"The patient is suspended with the Lynch suspension apparatus, the
papillomas are cleared out, and while 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 treatment of an angioma of the larynx occurring
in a child. The growth caused "dyspnea which would have been very
difficult to benefit in any other way. The angioma was entirely cleared
up by the external application of radium."

3. Chronic Infections. Laryngeal Tuberculosis. — The results of treat-
ment of this condition have varied. In a case of laryngeal tuberculosis
treated in conjunction Avith Dr. 0. 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 with two millimeters of lead and placed at a dis-
tance of two centimeters were applied for thirty hours in periods of fif-
teen hours each.

Technic of Laryngeal Applications. — Surface Radiations over the Lar-
ynx.— It is frequently possible to influence favorably benign and malig-
nant tumors of the larynx by surface radiations alone. Benign tumors
may be cured by surface radiations alone but malignant lesions require
intralaryngeal radiations as well. At a distance of 3 cm., 250 me. screened
with 2 mm. of lead may be applied for twenty hours in periods of ten
or more hours each. Four hundred me. may be applied at a distance of
6 cm. for thirty hours in several periods.

Intralaryngeal Radiations. — 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
ending in a holder (Fig. 164) securely grasp the screen containing the
emanation tube which is thus placed 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 reinforced with anes-
thesine powder insufflated into the pharynx and larynx. In order to
introduce 'the emanation tube into the larynx, the applicator is seized by
the thumb-plate (Fig. 163) and the screen is inserted into the larynx
with the aid of the laryngeal mirror. Except in the case of papilloma of

300

RADIUM THERAPY

the larynx in children, neither direct laryngoscopy nor 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

Fig. 162. — The Freer clamp for the intralaryng-eal application of radium. The clamp seen from
above affixed to the forehead plate of the head-strap and open to receive the tubular stem of the
applicator.

F.A.HARDY*Cd

Fig. 163, — The applicator held in the jaws of the Freer clamp with the screen containing radium
emanation in the glottis as indicated by heavy dotted lines.

OPHTHALMOLOGY, OTOLOGY, AND LARYNGOLOGY

301

from ten to sixty minutes without retching or distress. The hollow stem
carrying the emanation tube is attached to an electric suction pump
which serves to keep the throat constantly free of saliva and secretions.
The use of moderately large doses is of great value in the treatment of
feeble patients. An exposure of 400 me. hours may be given in the course
of a week or more.

With intralaryngeal and surface radiations combined I have treated,
in conjunction with Dr. 0. T. Freer, 19 carcinomata of the larynx. 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 months. One case recently developed a metas-
tasis in the humerus but the larynx is clinically well. Of the remaining

FAHARDYsCO.

Fig. 1^4. — A, Enamel silver tube containing capillary glass emanation tube: B, Screen fastened
to tubular copper applicator at a — a by means of copper wire soldered 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; D, silver screen seen
on edge, fastened into notch of holder by No. 24 copper 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; /:, 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; /•', socket holder to hold screens for use in the glottis. The holders must be individually
made to fit each screen. The advantage of this holder lies in the firmness with which it grasps the
screen.

9 patients, seven were 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 case 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 the 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 reinforced 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, W. A. Wells, the writer, and others have found radium
of value in the treatment of certain cases of hypertrophied tonsils.

Simpson has used a double strength dermatological applicator contain-
ing 30 mg. of radium element. This was wrapped in rubber dam and
applied unscreened for one hour. Wells has inserted radium contained in
metal needles into the tonsil. In some cases, 100 me., screened with
1 mm. of silver plus 1 mm. of rubber may be applied for 1 hour to each
tonsil. The normal tissues of the throat must be carefully protected.

In selected cases, radium treatment may be substituted for operative
removal of the hypertrophied tonsil.

CHAPTER XIX
RADIUM IN DISEASES OF THE DUCTLESS GLANDS

A. LEUKEMIA

Renon, Degrais and Desbouis were among the first to use radium in
the treatment of myelogenous leukemia. The radium was applied di-
rectly over the spleen. After referring to twelve cases treated by other
French workers, these authors reported five cases under their own care
in which satisfactory remissions were obtained. Of the five cases re-
ported, death occurred in two, two years and two months after the first
exposure. Two cases were in good 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, which 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, Hay ward Pinch,
Ordway, Peabody and many others, including myself, in which a favor-
able influence has been exerted by radium. Giffin has reported thirty
cases and Peabody has observed thirty-six cases of leukemia in which
radium treatment was used. I 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 the spleen.

The beneficial effects of the radium treatment of leukemia are quite
uniform.

A certain degree of improvement occurs in the general condition of
practically all of the cases. Headache may be relieved and the "buzz-
ing" in the ears sometimes complained of may disappear. In certain
cases the improvement in the general condition is quite remarkable.
Even in the bedridden, sufficient improvement in the appetite and strength
may occur so that the usual occupation of the patient may be resumed.
The effect on the spleen is to reduce it perceptibly in practically all cases.
Frequently the spleen becomes almost .or quite nonpalpable. The spleen
usually shows the greatest reduction in size in about one or two months
from the beginning of the treatment.

The blood picture shows very definite effects of the treatment. The
number of leucocytes usually begins to decrease in from one to three
days after radium is applied and may progressively continue to diminish
for several days or even weeks after the exposure. In one of Peabody 's

303

304

RADIUM THERAPY

cases of myelogenous 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 days. Many other even more striking illustrations of the

Fig. 1<>5. — Chronic lymphatic leukemia. Greatly en',..:'^ '! OerTtOl ;i::'l .t\i!lary lymphatic glands.
White blood count 113,000. Photograph taken January 12, 1917. Patient referred by Dr. Charles A.
Elliott.

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* DISEASES OF DUCTLESS GLANDS

305

lute number is usually markedly diminished. The relative percentage
of small lymphocytes shows an increase after the reduction in the leuco-
cyte count but the absolute count of the small lymphocytes is much
diminished. The relative percentage of large mononuclears is usually
increased.

Fig. 166. — Patient in Fig. 165 showing rcmissioii of the disease after radium treatment. The
cervical glands have become practically normal and the axillary glands are markedly reduced. White
blood count 7,500. Photograph taken February 3, 1917.

In the majority of patients, there is usually an improvement in the red
blood count and in the percentage of hemoglobin. If hemorrhage, such
as epistaxis, purpura, etc., is present it usually ceases. While it has been
held by some that hemorrhage may even be caused by radium 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 effects 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
with 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 belief that
too large doses should lie avoided. The radium may be applied to differ-
ent areas of the spleen successively, or to the lymphatic glands, as tin-
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
(50 to 60 me. 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
sauze) was 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 weeks apart. Great symptomatic improvement
followed, although the patient died about eight months after the first
series of treatments. Giffin 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 wood. 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. My experience leads me to prefer
this latter method. Ordinarily 200 millicuries (1% me. to each square
cm.) screened with 2 millimeters of lead and at a distance of 3 centi-
meters may be used. An exposure of six hours twice weekly 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 DUCTLESS GLANDS 307

or until a satisfactory diminution in the leucocytes is evident. The
course may be repeated in six weeks hut may be given earlier or later as
thought advisable. It must be emphasized, however, that great judg-
ment is required in determining the size of the dose and the frequency
of its repetition. Various factors must be considered, these being prin-
cipally the effect of the treatment on the general condition, on the size
of the spleen and especially the effect on the white blood count. Radium,
applied to the spleen in the manner indicated, may cause a constitutional
reaction, such as nausea, vomiting, malaise and headache. These symp-
toms usually pass off within twenty-four hours. An excessive amount
of treatment may result in marked leukopenia and an increase in the
anemia. These symptoms should 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 or 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 tubes.

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. Recurrences may take place
but 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 treated with radium,
splenectomy was performed when the reduction in the size of the 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 splenectomy,
although the patients may be made more comfortable by the operation.

In addition to the usual method of treating leukemia by exposing the
spleen or lymphatic glands to surface radiations, a few workers have inves-
tigated the effects of radium when administered constitutionally. The re-
sults of this method of treatment have varied. Von Noorden and Falta
did not obtain beneficial results from the inhalation of radium emanation.
Proescher and Almquest injected soluble radium salts intravenously but
without marked benefit. Falta, Kriser and Zehner obtained remissions in
leukemia by the injection of thorium X, the action of which is similar
to that of radium. Radioactive deposit dissolved in water has also been
injected by a few workers. For the present, however, the method of
treatment of leukemia by exposure of the spleen or lymphatic glands to
surface radiations is to be preferred. Radium treatment is probably the
method of choice, in the treatment of leukemia at the present time. It

308 RADIUM THERAPY

sometimes succeeds in producing remission when all other methods, in-
cluding the use of benzol and x-rays, have failed.

B. HODGKIN'S DISEASE (LYMPH ADENOMA)

The affected glands in TTodgkin's disease frequently disappear very
promptly. In only one of eleven cases treated have we seen rebellious-
ness to the treatment. In two cases of that form of the disease, in which
nodular tumors appear on the bones (sternum, skull bones, etc.) very
marked susceptibility to the radium rays was noted. Tn several cases
we have seen remissions which have persisted for more than one year.
It is probable, however, that recurrence takes place sooner or later in
most cases. The treatment 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 (nausea, malaise)
which frequently follows heavy doses.

Four hundred millicuries screened with 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 over each area. The concentration of the radium may
be. 5 me. per square centimeter. Treatment may be given twice weekly
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 disturbance is slight.

C. GOITER

In the various types of goiter, radium treatment may be helpful.

In the simple parenchymatous type there is general enlargement of
the thyroid gland and the follicles, Avhich are usually newly formed.
contain colloid material. The results of radium treatment in this type
may be very beneficial.

The vascular type of enlarged thyroid may also respond well. In
favorable cases the neck may decrease in size several centimeters.

In the type of goiter in which large cysts occur, the walls of the cysts
frequently undergoing calcification, but little benefit is to be expected
from radium treatment.

Exophthalmic Goiter

Abbe, of New York, treated the first case of this disease with radium
in 1905. Following Abbe's report many other authors, including Aikens,
Burrows, Clagett, and Dawson Turner have reported favorably upon the
results of radium treatment. Radium may be used when the ordinary
methods of treatment prove unavailing or when operation is considered
inadvisable. In cases that respond favorably, improvement in all the
toxic symptoms may be noted in three to six weeks and in some cases,
very much more quickly. Tachycardia, tremor and exophthalmos are

RADIUM IN DISEASES OF DUCTLESS GLANDS 309

frequently diminished. The high blood pressure which is so frequently
present is often diminished and after several courses of treatment may
become practically normal. In some cases operation may be performed
if thought advisable after a certain degree of improvement has been
brought about by radium. It has been held that operation is rendered
more difficult by previous radiation. It must be remembered that strik-
ing remissions may occur in the natural course of the disease so that it
is sometimes difficult to judge of the effects of treatment.

Technic of the Treatment of Goiter. — The method of treatment involves
the use of moderately deep penetrating rays. Aikens, who has observed
about one hundred cases, advises in the .beginning of treatment a total
exposure of from 150 to 360 milligram hours. Subsequent courses of
50 to 150 milligram hours may be given. Many other authors use larger
doses than those just indicated. I ordinarily use not less than 150 milli-
curies, screened with 2 millimeters of brass and placed at a distance of
3 centimeters. Five millicuries may be concentrated on each square
centimeter. A total exposure of twenty hours on each of three areas
is given. In certain cases of large goiters we use 500 millicuries con-
centrated on an applicator having a superficial area of fifty square centi-
meters. This is screened with 2 millimeters of brass and applied at a dis-
tance of 6 centimeters. An exposure of fifteen hours may be given to each
lobe and to the isthmus of the thyroid. The three exposures should be
given several clays apart. 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. Improvement then usually
sets in and by the end of a month or six weeks may- be very decided.
The course of treatment may be repeated at intervals of six or eight
weeks. Subsequent courses of treatment may be of less intensity. The
amount of treatment may be regulated by the basal metabolism test.

In addition to the radium treatment, supplementary measures includ-
ing rest, diet and suitable drugs should be used.

D. ENLARGED THYMUS GLAND

Brayton and lleublein have treated with radium 34 cases of enlarged
thymus gland in children. In every instance there followed a prompt
and lasting disappearance of all symptoms. These authors state that
"every infant who lias 'queer spells' who has habitual attacks of cough-
ing, choking, dyspnea, or cyanosis should have an x-ray examination of
its chest in the hope of finding a condition (pathologically enlarged
thymus) which is so easily and satisfactorily cured." Their technic
consisted in using 100 miligrams of radium element screened with 0.5
mm. of silver. The radium was applied at a distance of one half inch
from the skin to four different points over the thymic area and allowed
to remain for two hours over each point.

CHAPTER XX
RADIUM IN INTERNAL MEDICINE

Radium <nid thorium X are the Iwo principal radioactive substances
used in internal medicine. The biologic 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 with radium explains its more intense biologic effect. The
investigations of the effects of thorium 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 administration and elimination of radium,
(b) its physiologic effects, (c) morphologic changes in the tissues caused
by radium, (d) therapeutic indications.

A. THE ADMINISTRATION AND ELIMINATION OF RADIUM
(1) The Administration of Radium

Radium may be administered either in the form of radium salts,
radium emanation or the active deposit. The effects of both 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 element. Less experience has been had with 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 giving, by mouth, water con-
taining the salt in solution or by the injection of a solution of the salt
intravenously. The drinking water 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

Radium emanation may be administered by means of drinking water
in which the emanation is dissolved, by inhalation, or by baths. Radium
emanation in solution may be given by mouth. The strength of "emana-
tion drinking water" is usually 1.5 to 2 millicuries per liter of water.
About 250 c.c. is the usual daily dose. If the inhalation method is \\sed
the patient may sit in a small room known as an "inhalatorium," the
air of which is impregnated with the emanation mixed with oxygen.
The air which is breathed is purified by being passed over caustic soda
and is then returned into the room. This is objectionable on account of
the respiratory products which are continually being reinhaled. By
another method, the patient inhales a stream of air or oxygen mixed with
the emanation and exhales it into the open air by a valve arrangement.
This is a better though more wasteful method. The quantity of emanation
in the air inhaled varies from 0.003 to 0.3 microcurie per liter of air.
Inhalation treatments may last an hour or more. The results of treat-
ment by the inhalation method seem to differ in no wise from those
obtained by the administration by mouth of emanation drinking water
and the latter is certainly the more convenient and economical method.
Gudzent, Falta and some others, however, make considerable use of the
inhalation method. Emanation baths may also be given, but the good
effects claimed seem to be due solely to the emanation that is inhaled.

Administration of Radioactive Deposit

II. ,1. Bagg has investigated the pathologic tissue changes accompany-
ing the injection of the active deposit. White rats were injected intra-
venously and subcutaneously. Pathologic changes in the various or-
gans— liver, lungs, kidneys, adrenals, spleen, bone marrow, brain and
vascular system — were noted and described in detail. Among the effects
were fatty degeneration in the liver, granular degeneration and erosion
of the kidney cells, destruction of the cells of the bone marrow and their
replacement by blood, and congestion and hemorrhages in practically
all of the organs. A similarity was noted in the tissue reaction due to
radium applied externally and that due to the active deposit when in-
jected subcutaneously or intravenously. Doses of less than ten milli-
curies of radium emanation were not fatal to the experimental animals.
Larger doses caused death within a few hours or days. The doses used
in human beings have varied from fifty to two hundred and fifty milli-
curies of active deposit dissolved in two to six c.c. of solution. In one
ease severe toxic symptoms developed after the injection of 250 me.
Similar doses in other patients produced no ill effects.

(2) The Elimination of Radium

Prom our knowledge of its chemical affinities it would be expected that
radium, when held in the body, would be found wherever the other

o!2 RADIUM THERAPY

alkali earth elements are found, inasmuch as radium is an element closely
akin to calcium, barium and strontium. According to Seil, Viol and
Gordon, analysis of the dead tissues of animals and humans who have
had radium administered has shown that the bones, as might be expected,
do contain the highest concentration of radium. Following the bones,
in the order of radium content, come the liver, lungs, blood vessels and
spleen. Cameron, Viol and Proescher examined dead tissue from a human
being who had suffered from uterine cancer. The patient had received
1 mg. of radium element intravenously 3 months prior to her death.
These authors found that the cancerous tissue did not contain a greater
relative amount of radium than other tissues and not as much as the
bones and some other organs.

The method of the elimination of radium has been studied by Belling-
ham-Smith, Brill and Zehner, Seil, Viol and Gordon, and many others
with general agreement as to the main trend of the observations.
Bellingham-Smith found that radium injected into mice was excreted
principally by the small and large intestines and to a lesser extent by
the urine. According to this author, soluble salts, however adminis-
tered, are rapidly eliminated, mainly by the intestine, but also by the
urine. Insoluble salts, given by the mouth, are directly excreted by the
bowel without being absorbed, but when given by injection are excreted
very slowly by the bowel. After administration of the emanation in
solution, a general but brief radioactivity is caused throughout the or-
ganism. Elimination, which takes place almost entirely by the Kings, and
to a very slight extent by the kidneys, is complete in 4 hours. Ketron
found that only a very minute quantity (0.025 micrograms) was elimi-
nated by the skin after the intravenous injection of 100 micrograms.
Seil, Viol and Gordon have made one of the most extensive studies of the
excretion of soluble radium salts when administered both intravenously
and by the mouth. The following ^conclusions were reached by these
authors: The principal part of the radium is excreted by the feces with
either method of administration. Most of the remainder is eliminated
by the urine. A minute amount is eliminated by the lungs in the form
of radium emanation which is being constantly formed by the disintegra-
tion of the radium held in the body. As might be anticipated, when
radium is administered by the mouth a smaller proportion of the ex-
creted radium is eliminated by the urine than when it is injected intra-
venously. From 25 to 35 per cent of the radium taken by mouth remains in
the body for 4 or 5 days after ingest ion. If radium is injected intravenously,
55 to 65 per cent remains for the same length of time. From this time
on, the rate of elimination is about the same whether ingested or injected.
By the 10th day the daily rate of excretion is less than 1 per cent. As
a result, there is an exceedingly slow elimination of the balance of the
radium, the process going on for months. The first rapid elimination

RADIUM IN INTERNAL MEDICINK 313

takes place before the radium has become "fixed" in the tissues. When
"fixation" of the radium has taken place all methods of elimination are
much slower. By fixation is meant that the radium that is not eliminated
at once is probably carried in the blood stream in solution or suspension
until it becomes absorbed by the various tissues in proportion both to
their alkaline earth salt content and to their accessibility by the blood.
On the basis of the foregoing studies, these authors suggest a rational
method of maintaining radium in the system. If, for example, it is
desired to maintain about 50 micrograms of radium element in the body,
one may give an intravenous injection of about 100 micrograms. After
the lapse of about ten days, 2 micrograma may be given every few days
by mouth to replace that which is eliminated.

B. PHYSIOLOGIC EFFECTS OF RADIUM

Experiments on different animals as well as on human beings to deter-
mine the effects of radium have been carried out by Bellingham-Smith,
Cameron and Viol, Dominici and Faure-Beaulieu, fJudzent, Jaboin,
Proeseher, Salant and Meyer, Wickham and Degrais and many others.

We may first consider the effects of therapeutic doses. These effects may
bo discussed under the following headings. (1) the general physiologic
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 patients 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 experienced.
The majority of patients taking radium emanation solution have a
definite diuresis and a slight laxative effect is sometimes observed. Some
patients experience a definite so-called "reaction." S. Lowenthal first
called attention to this phenomenon. The reaction is characterized by
an aggravation of symptoms, after a certain amount of treatment has
been given. There may be, e.g., an exacerbation of any joint symptoms
that have been present. General disturbances, including "tired feel-
ings." "malaise." and a desire for sleep, may occur. In other patients
there may be excitement and sleeplessness. These symptoms pass off
after a time if the treatment is discontinued. According to Gudzent,
these phenomena are frequently of favorable 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 the heart became di-
lated and its action arrested. By rinsing out the heart with normal

314 RADIUM THERAPY

Ringer's solution, its normal activity returned. The heart showed less
activity with each experiment, indicating according to this investigator, a
lowered resistance. In mammals, however, Plesch and Karczag could not
duplicate these results. Zwaardemaker has described a new and hitherto
unknown effect of the radiations on the heart. This 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 was then radiated with a few milligrams of radium for thirty
minutes it again began to beat. If a certain quantity of uranium salt
was added, the heart again stopped. Renewed 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 drawn from them.

Certain of the experiments on blood pressure have a practical aspect.
In various experiments on dogs and human beings carried out by Loewy,
Plesch and Gudzent with inhalations of radium emanation and injections
of thorium X, the blood pressure in general was markedly decreased.
According to Gudzent, the decrease in blood pressure, which may be
lowered for long periods and may even become and remain normal in
certain gouty and arthritic patients, is due to the destructive effect on
the vasoconstrictor siibstances 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 pneumonia. Plesch has reported an acceleration
and increase of respiration.

(3) Effects on Metabolism

The influence of the administration of radium on metabolism has been
studied by Falta, Gudzent, Krieg, Lowenthal, Plesch, Rosenbloom,
Wilke, and many others. The investigations tend to show that the excre-
tion of uric acid and of purin is increased. The entire nitrogen excretion
is also increased. Following an injection of one hundred micrograms of
radium element intravenously, Rosenbloom found that there was a con-
siderable increase in the ethereal sulphur output. In three patients
whose metabolism while taking radium emanation water (3 ounces, five
times a day or 20,000 Mache units in all) was studied by McCrudden,
no marked metabolic changes were made out. Only one definite change
was observed — a slight increase in the rate of creatinin excretion. The
results of the studies of various authors have shown, in general, marked
differences in the effect on metabolism and in some patients little or no
effect has been observed. We may also mention here the investigations
of Knudson and Erdos who studied the metabolism of a case of leukemia
that was being treated by surface applications of radium over the spleen.
The conclusions of these authors were as follows: The excretion of

RADIUM IN INTERNAL MEDICINE 315

nitrogen, urea, ammonia and phosphates was enormously increased after
the application of radium. The uric acid output was only slightly in-
creased compared to the other nitrogenous bodies. Surface applications
of radium over the 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 phosphates was remarkable,
there being at times an increase of four hundred per cent over the
excretion observed at the beginning of treatment.

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 first apparent which indicate
injury to the organism. The animal eats, sleeps, moves about, and passes
urine and stools in a normal manner. In a few days, however, the picture
changes. The animal appears to be ill, refuses 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 radium as a
toxic substance.

Experiments with barium, an analogous chemical element, do not bear
out this view. To cause death with barium one must use a dose several
hundred times greater than the lethal dose of radium. The toxic symp-
toms are also dissimilar. The death of the animal, therefore, after a
sufficient dose of radium internally, appears to be due solely to the effect
of the radiations. Gudzent 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 body weight. For a body of 70 kilograms the
fatal dose would thus be about 0.5 mg. According to the experiments
of Cameron, Viol and Proescher, this estimate is low. These authors
have carried out an extensive series of experiments with injections of
soluble radium salts. They state that they have used doses as high as
five milligrams of radium element in 2 c.c. of normal salt solution intra-
venously in human beings and have never seen from these doses the
slightest ill effects. They regard doses of fifty to one hundred micro-
grams intravenously as therapeutically correct and absolutely safe. By
the inhalation method, Proescher and Viol found that a concentration
of 26 millicuries of emanation per liter of air (70 million Mache units)
produced death in animals. Lazarus-Barlow exposed animals to the
gamma rays of five grams of radium bromide. The minimum lethal dose
of gamma rays for the rat was an exposure of six hours, the animal
dying about forty-two hours later. For the rabbit an exposure of nine
to ten hours was necessary.

316 RADIUM THERAPY

C. MORPHOLOGIC CHANGES IN THE TISSUES CAUSED BY

RADIUM

Inasmuch as the effects of radium taken internally are due to the
action of the rays, one would expect that similar changes would 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 toto, however, effects may be produced that are practically
identical with those caused by the administration of radium.

We may now consider the changes produced in different 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 (%ooi> mg.) or thorium X (1/ioo<> to
]/!oo mR-) &re 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 (Gudzent 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 disappear from the blood altogether just prior
to the death of the animal.

According to Proescher and Alniquest, thorium X has a more destruc-
tive effect on the leucocytes than radium. With superfatal doses of
radium these authors were unable to destroy all the circulating leu-
cocytes or myeloid cells of the bone marrow.

Erythrocytes

In contradistinction to the leucocytes, the red blood cells are not
markedly sensitive to injections of radioactive substances. After small

RADIUM IN INTERNAL MEDICINE 317

doses, no change at all, as a rule, is seen. Sometimes, however, there
may be an increase in number of erythrocytes as observed by Dominici
in the horse and Brill and Zehner in dogs and rabbits. The last 2
authors found that the erythrocytes were increased in some cases to 13
million per c.c. This increase may be maintained for weeks. The hemo-
globin was also increased but not proportionally to the increase in the
number of erythrocytes. Proescher and Almquest have reported similar
results. By the injection of larger doses of thorium X, the red blood
cells may be damaged so that both a numerical decrease and a decrease in
hemoglobin may occur.

In pathologic conditions, such as secondary and pernicious anemia,
the crythrocytps appear to be more sensitive than in normal individuals.
Proescher found that in such cases the injection of soluble radium salts
(0.1 to 0.4 mg.) increased the red blood cells to normal in a few days.
Oudzent has reported the same effect from the injection of small doses of
thorium 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 knowledge 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 been described in a previous chapter.

Suprarenal Glands

Falta and his coworkers and later von Domarus and Salle called at-
tention to the changes produced in the suprarenal gland and its func-
tions. Injections of thorium X produced, in general, 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 and large doses,
after an initial increase, caused a decrease. In certain cases, the blood
pressure rose again but did not attain to the point initially present.

Other Organs

The effects of injections of radioactive substances on other organs —
heart, kidney, pancreas, etc. — are much less pi-onounced than on the
previously mentioned structures. Traces of injury to the cells of certain
areas may be detected but these changes are never of a general nature.
Functional disturbances probably occur but these have not been as yet
sufficiently investigated.

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 Ijght 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. Considerable quantities could be borae
without any of the previous symptoms (leucopenia, anemia, loss of
weight) 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.

D. THERAPEUTIC INDICATIONS

The fullest details as to the use of radium and other radioactive sub-
stances in internal medicine are to be found in the recently published
monograph of Falta.

Among the many diseases in which radium has been used with alleged
benefit are the following:

1. Arthritis deformans, articular rheumatism (subacute and chronic)
and various other types of arthritis.

2. Gout.

3. Myalgia ("muscular rheumatism"), neuralgia and neuritis (sciatica,
tabetic pains, etc.).

4. "High blood pressm-e," arteriosclerosis, angioneurotic edema, neu-
roses of the heart, myocarditis.

RADIUM IN INTERNAL MEDICINE 319

5. Certain chronic inflammatory and suppurative 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).

9. Malignant disease.

1. Arthritis Deformans. — It has long been the custom for sufferers
from chronic joint diseases to visit springs in different parts of the world
and drink the waters. With the discovery that most of these springs
contained radium emanation in solution it became of great interest to
determine the effect of radioactive substances artificially prepared. It
may be noted that none of the springs at the various health resorts con-
tains more than the most minute quantity of radium emanation (about
1 to 30 millicuries per million quarts). It would seem, therefore, that
radioactive substances in doses sufficient to produce definite physiologic
effects might be of even greater benefit. Hayward 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 was relieved and the mobility of the joints
was increased provided no bony or cartilaginous changes had occurred.
In some cases the results were quite remarkable. Cameron and many
others have also seen favorable results in various types of arthritis.
Gudzent, who 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 Gudzent.

2. Gout. — Falta, Gudzent and others have reported favorable results
in the treatment of gout. The last named author states that of 86 cases
who had exensive treatment (emanatorium inhalations, "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 report 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 reports (Falta, Gudzent, Sommer, Kemen, Strasburger, etc.).
Gudzent has never seen benefit, however, in neuralgia of the trigcminus.

320 RADIUM THERAPY

4. High Blood Pressure. — The reduction of high blood pressure has
been observed by many authors. Gudzent states that in some cases the
blood pressure may be permanently reduced. Other authors, however,
doubt the' permanency of any reduction that may occur. Hay ward
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, the field for possible error in the interpretation of results
is, of course, very great.

5. Chronic Inflammatory Processes. — Lachmann states that he has seen
good 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. Blight's Disease and Diabetes. — Benefit has been reported by cer-
tain authors in these disorders.

7. Pernicious Anemia. — Proewher 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 of 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 considerable periods of time.

8. Dermatoses. — Individual reports of good effects in psoriasis and
scleroderma have been made.

9. Malignant Disease. — Good effects have been reported by some
authors from the administration 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 the writer that for the .present
at least we must rely in malignant disease solely upon the effects of local
radiations with radium rather 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, normal structures may be seriously injured.

The experimental work referred to above, i.e., the injection of active
deposit, etc., is of course valuable from a scientific standpoint.

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,

(d) certain painful affections, 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
when 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 caused 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 sufficient 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 they 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 with radium keratoses. Sub-
jectively the affected finger ends may show "anesthesia, paresthesia of
varying degrees, tenderness, throbbing and even pain. The persistence
of such effects is noteworthy." (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 probably a feeling of undue ex-
haustion noted at the end of the day. In women, menstrual disturbances
may occur. At first menorrhagia may be present. The menstrual func-
tion may then become irregular and amenorrhea may result. Normal

322

PROFESSIONAL INJURIES DUE TO RADIUM 323

menstruation returns, however, after a somewhat prolonged absence from
radium work. Many 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 by a relative and absolute lymphocytosis, which was present 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 therapeutic injections of radium.
Others who have studied the blood changes in radium workers have
found that leukopenia is practically always produced by persistent ex-
posure to the gamma rays. Mottram and Clarke investigated the leu-
cocytic blood-content of twenty laboratory and clinical workers engaged
in handling considerable quantities of radium. The polymorphonuclear
leucocytic and the lymphocytic blood content of all were found to be
decidedly below normal. The 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 upon
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 thousand 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 white 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, although the possibility of untoward effects
must be borne in mind. The constitutional effects of the gamma rays
can be minimized or obviated by a sufficient amount of care in handling
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
ordinary surgical tissue forceps, except that the radium forceps are
twelve inches long (Fig. 22).

With these the radium tubes as well as the large radium pads can be
conveniently grasped. Another type of forceps has three prongs at
one end, with which even the smallest tubes may be picked up and held
securely (Fig. 23). (b) Special "holders" for screwing together the dif-
ferent parts of screens or other radium apparatus (Figs. 25 and 26).
(c) A special instrument by means of which one may wrap up the radium
tubes in dental rubber dam without handling them with the fingers

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
which the technicians may sit while manipulating the radium tubes.
We have devised also a movable apparatus for the protection of the opei'-
ator. This consists of an upright heavy 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

AJibe, Robert: Exophthalmic Goitre Reduced by Radium, Arch. Boeutg. Kay, 1904-

1905, ix, 214-218.

Radium in Therapeutics, Boston Med. and Surg. Jour., 1904, el, No. 2, p. 53.
Action du radium sur quelques tumours particulieres, Le Radium, 1905, ii, 55-57.
Radium in Surgery, Jour. Am. Med. Assn., July 21, 1906, pp. 183-185.
Illustrating the Penetrating Power of Radium, Arch. Roentg. Ray, 1907, xi, p. 247.

• The Specific Action of Radium as a Unique Force in Therapeutics, Med. Rec.,

New York, 1907, Ixxii, p. 589-594.

Radium in Surgery, Arch. Roentg. Ray, 1910, xiv, 277-281.
Radium as a Specific in Giant Cell Sarcoma, Med. Rec., New York, 1910, Ixxvii,

1-5.
The Use of Radium in Malignant Disease, The Lancet, London, August 23, 1913,

clxxxv, 524-527.
Die Anwendung von Radium bei Karzinom und Sarkonij Strahlentherapie, 1914,

iv, 27-35.

The Therapeutics of Radium, Canad. Pract. and Rev., 1914, xxxix, 197-212.
The Efficiency of Radium in Surgery, Ohio State Med. Jour., August, 1914, pp.

461-465.
Radium Beta Rays, the Efficient Factor in Repressive Action on Vital Cells, Med.

Rec., New York, November 28, 1914, Ixxxvi, 909-913.
— - Uterine Fibroids, Menorrhagia and Radium, Med. Rec., New York, March 6, 1915,

Ixxxvii, 379-381.
Lymphangioma and Radium, Med. Rec., New York, August 7, 1915, Ixxxviii, 215-

217.
Roentgen Ray Epithelioma Curable by Radium. An Apparent Paradox, Jour. Am.

Med. Assn., July 17, 1915, Ixv, 220-221.

— Radium Efficiency in Nonmalignant Surgical Conditions, Med. Rec., New York,

July 8, 1916, xc, No. 2, pp. 47-50.
Abelsdorff, G.: Die Wirkung des Thorium X auf das Auge, Klin. Monatsbl. f. Augeuh.,

1914, liii, 321-334.

Alrams, Marc V.: The Role of Radium in Surgery, Med. Rec., New York, Septem-
ber 10, 1921, c, 457-459.
Adler: Morphologische Kennzeichen fiir die Radiumempfiiidlichkeit der Karzinome

des weiblich gcnitales, Zentralbl. f. Gynak., 1916, No. 33, pp. 673-680.
Aikins, W. H. B.: The Value of Radium in Malignant Gynecological Conditions,

Canada Lancet, Toronto, 1914, xlvii, 742-748.
Personal Experiences with Radium, Canad. Pract. and Rev., September, 1914,

xxxix, pp. 535-545.
Radium and Trichloracetic Acid in Dermatology, Canad. Pract. and Rev., October,

1915, xl, No. 10. pp. 479-489.

Exophthalmic Goitre with Special Reference to the Etiology and Treatment with

Radium, New York Med. Jour., 1916, civ, 49-53.
The Radium Treatment of Malignant Disease of the Lip and Skin, Canad. Pract.

and Rev., April, 1917, xlii, 142-148.
The Established Value of Radium as a Therapeutic Agent, Canad. Pract. and

Rev., June, 1917, xlii, 237.

— Radium in Tuberculosis of the Skin, Canad. Pract. and Rev., February, 1918, xliii,

42-55.

Radiurntherapy in Hyperthyroidism with Observations on the Endocrinous System,
Radium, March, 1919, xii, No. 6, pp. 81-90.

• Sarcoma Following Injury, Successfully Treated with Radium, Urol. and Cutan.

Rev., 1922, xxvi, 33.

XOTK: The authors' names are arranged in alphabetical order throughout this bibliography,
but the subjects under each name are arranged chronologically.

325

326 RADIUM THERAPY

— and Simon, K. M. B.: The Histological and Clinical Changes Induced by Radium

in Carcinoma and Sarcoma, Dominion Med. Month, September, 1914, pp. 97-

107.
Albamus: Die Methodik der Eadiumbestrahlung in der Nasen-, Mund- Eachenhb'hle,

im Kehlkopf, in der Luftrbhre und im Schlund, Deutsch. med. Wchnschr., 1912,

No. 17, pp. 805-808.
Allen, Bundy: Squamous Celled Epithelioma Responding to Roentgen and Radium

Tlierapy, Radium, February, 1919, xii, No. 5, pp. 65-69.
Allmann: Die Behandlung des Karzinoms mit Mesotliorium, Deutsch. med. Wchnschr.,

1913, xxxix, No. 49, pp. 2402-2403.
• Zur nichtoperativen Karzinombehandlung, Strahlentherapie, 1914, iv, 620-035.

— Zur Behandlung des Jebiirmutterkrebses, Zentralbl. f. Gyniik., 1916, No. 7, pp.

129-135.
Allport, Frank: Some Remarks Concerning Vernal Conjunctivitis, Ophthal. Rec., 1917,

xxvi, 395-396.
Alman, B. D.: Radiumtherapy of Cancer, Vestnik. Oftalmol., Moskva, 1908, xxv, 169-

175.
Alton, W. L. S.: Report of the Chemico-Physical Laboratory, The Radium Institute,

London, in Report of Radium Institute, London, From January 1, 1917 to

December 31, 1917, pp. 34-36.
AnspacJi, Brooke M.: The .Treatment of Advanced Carcinoma of the Cervix with

Radium, Am. Jour. Obst., July, 1915, Ixxii, 97-101.
Apolant, H.: Ueber die Riickbildung der Mausekarzinome unter dem Einfluss der

Radiumstrahlen, Deutsch. med. Wchnschr., 1904, No. 31, pp. 1126-1127.

— Ueber die Einwirkung von Radiumstrahlen auf das Karzinom der Mause, Deutsch.

med. Wchnschr., 1904, No. 13, pp. 454-456.
Arendt: Ueber die Wirkung der Radiumstrahlen auf inoperable Uteruscarcinome,

Berl. klin. Wchnschr., 1911, xlviii, 333-335.
Arleninoff, Gregor: Ueber Radiumtherapie bei Bosartigen Gesehwiilsten, Inaug. Diss.,

Berlin, 1912.

Armstrong, W.: Radium Water Therapy, Brit. Med. Jour., April 29, 1911, pp. 992-993.
Arneth: Die Thorium-X Wirkung auf das Blutzellenleben, Deutsch. med. Wchnschr.,

1913, No. 16, pp. 733-737; ibid., No. 17, pp. 787-792.

— Thorium-X bei pernizioser Anamie, Berl. klin. Wchnschr., 1914, No. 4, p. 153.
Arronet: Ueber Schlammbader und Radioaktivitat, St. Petersburger med. Wchnschr.,

1905, Nos. 42-43, pp. 443-447.

Art-maim, P.: Ueber radio-aktive quelhvasser und deren messung, Cor.-Bl. d. Ver.
deutsch. Aerzte in Reichenberg, 1910, xxiii, No. 5, pp. 1-14.

— Radioaktives Trinkwasser, Umschau, Frankfurt-am-Main, 1910, xiv, No. 20, pp.

387-388.

Ueber das vcrhalten von radioaktiven Wasscr beim Stehen in geschlossenen Gefas-
sen, Ztschr. f. Balneol, Klimat., etc., 1910, iii, 99-102.

— Radioaktivitat des Meerwassers, Ztschr. f. Balneol. Klimat., etc., 1911-1912, iv,

605-610.
Arzt, L., and Scliramek, M.: Zur intrntumoralen Radiumbestrahlung maligner Ge-

schwulste, Fortschr. a. d. Geb. d. Rontgenstrahlen, 1914, xxii, No. 2, pp. 159-

178.
Aschlinass, E.: Die Wirkung der Becquerel-Strahlen auf Bakterien, Verh-Gesells.

deutsch Naturf. u. Arzte., Leipzig, 1902, Ixxiii, 467-468.

— Die bakterizide Wirkung der verschiedenen in der Gesamtemission des Radiums

enthaltenen Strahlenarten, Verh. Gesells., deutsch, Naturf. u. Aertze., Sektion

fiir Dcrmatol. u. Syphilis, 1904, Ixxvi, 405-406.
— , and Campari, W.: Ueber den Einfluss dissociircnder Strahlen auf organisirte Sub-

stanzeu, insbesondere iiber die bakterienschadigende Wirkung der Becquerel-

strahlen, Pfliiger 's Arch, f . d. ges. Physiol., 1901, Ixxxvi, 603-618.
Aschoff, Karl: Das Vorkommen von Radium in den Kreuznacher Solquellen, Miinchen.

med. Wehnschr., 1905, No. 11, pp. 517-518.

— Dosierbare Radiumemanations-therapie, Ztschr. f. Balneol., Klimat., etc., 1909,

ii, No. 6, pp. 190-192.

— Die Radioaktivitat der Kreuznacher Solquellen, Ztschr. f. Balneol., Klimat., etc.,

1911-1912, iv, 620-624.

Die Radioaktivitat dcr Kreuznacher Solquellen und die therapeutische Verwendung
der aus denselbengewonnenen radioaktiven Substanzen, Med. Klin., 1908, iv,
No. 27, pp. 1031-1032.

BIBLIOGRAPHY 327

— , Kronig, and Gauss: Zur Frage tier B<>einflussbarkeit tiefliegender Krebse durch
Strahlende Energic, Munchen med. Wchnschr., 1913, Ix, 337-341 and 413-417.

Aubertin, Ch.: Action des Rayons X Sur Le Sang et La Moelle Osseuse, Arch. d. Med.

exper. anat. path., 1908, xx, 273-288.

Modification du sang ehez les Radiologues Professionels, Compt. rend. soc. d.
biol., 1912, Ixxii, 84-86.

• and Bcaujard: Modifications immediates du sang leucemique sous 1 'influence do la

radiotherapie, Compt. rend. Soc. d. biol., Paris, 1904, Ivii, 982-984.

— and Delamosse, A.: Die Wirkung des Radiums auf das Blut, Zentralbl. f. inn.

Med., 1908, xxix, No. 42, pp. 1037-1039.
Auerbach, N.: Die Bchandlung von Gicht und Rheumatismus mit Radium, Discussion

in Verhandl. d. Berl. med. Gesellsh., 1911, xlii, 21-22.
Augustin, B., and Szendeffy, A. von: Die Bakterizide Eigencshaft radioafctlver Sub-

stanzen, Pest, med-chir. Presse., 1910, xlvi, 177.
Axmann: Ueber Radioaktivierung und ein neues Radiumpraparat (Radiophor.)

Deutsch. med. Wchnschr., 1905, xxxi, No. 30, pp. 1192-1193.

— Beseitigung der durch Radiumstralilen bewirkten Gefasserweiterungen, Munchen.

med. Wchnschr., 1907, No. 38, p. 1877.

— Kalte und Uviolbehandlung in Verbindung mit Riintgen und Radium, Munchen.

med. Wchnschr., 1936, No. 4, p. 123.
Ayres, Wmficld: Radium in Cancer of the Bladder, New York Med. Jour., February

20, 1915, ci, 345-347.
• — The Effect of Intravenous Injections of Radium on a Persistent Positive Wasser-

mann Reaction, Med. Ree., New York, October 9, 1915, Ixxxviii, 610.

liaeger: Ueber die physiologische Wirkung der Becquerelstrahlen, Ztschr. f. allg.

Physiol., 1904, iv.
Sagg, H. J.: Pathologic Changes Accompanying the Injection of an Active Deposit of

Radium Emanation. Intravenous and Subcutaneous Injections in the White

Rat, Jour. Cancer Research, January, 1920, pp. 1-24. Abstracted in Surg.,

Gynec., and Obst, May, 1920, xxx, 381.
The Response of the Animal Organism to Repeated Injection of an Active Deposit

of Radium. Emanation, Jour. Cancer Research, October, 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, September, 1921, viii, 536-547.
liagge, I. : Eine kombinicrte biologische-radiologische Methode der Cancerbehandlung,

Ztschr. f. Krebforsch., 1910-11, x, 251-266.
liahr, F.: Zur Frage der kiinstlichen Erzeugung von y-Strahlcn radioaktiver Substanzen

mittels Roentgenrohren, Strahlentherapie, 1914, v. 427-430.

Bailey, Harold C.: Radium in Uterine Cancer, Jour. Am. Med. Assn., July 14, 1917,
Ixix, No. 2, p. 145.

• and Bagtj, H. J.: Radium Therapy in Vulval and Vaginal Cancer, Abstracted in

Jour. Am. Med. Assn., 1921, p. 314.
- and — ; Vulval and Vaginal Cancer Treated by Filtered and Unfiltered Radium

Emanation, Am. Jour. Obst. and Gynec., December, 1921, ii, No. 6, 587.
— , and Quinnby, Edith: The Use of Radium in Cancer of the Female Generative

Organs, Am. Jour. Obst. and Gynec., 1922, iii, 117-133.
Baisch, K.: Erfolge der Mesothoriumbehandlung bei 100 Uteruskarzinomen, Munchen.

med. Wchnschr., 1915, No. 49, pp. 1670-1673.

liulthazard, V.: fitude physiologique et therapeutique des radiations emises par les
corps radioactifs et de leurs emanations, Arch, d 'electric, med., 1906 xiv,
403-414.
I'.amford, E. E.: Use of Radium in Surgery, Jour. Iowa Med. Soc., May, 1921, ix,

167.
Barcat: Deux cas d'epitlieliomas cutanes gueris par le radium, Bull, et m6m. Soc.

med. d. hop. de Paris, 1909, series 3, pp. 931-935.
Traitement d'un naevus vasculaire plan par le radium, Presse med., 1909, No. 20,

p. 174.
Vcrrues planes traitfies par le radium, Bull. Soc. franc, de dermat. et syph.,

Paris, 1910, xxi, 172-174.
Die Radiumthcrapie in der Dermatologie, Strahlentherapie, 1914, iv, 322-375.

o28 RADIUM THERAPY

Die Bndiurn thorapic maligner Tumoren, Strahlenthcrapie, 1914-1915, v, 51-69.
— • and Delaware, A.: Le radium dans le traitement des nevrolgies et dcs ncvrites,

Arch, d 'electric, med., 1908, xvi, 243-249.
Barduszi, D.: Sul valore terapeutico delta radio-attivita di alcune acquo termominerali,

ed in particolar modo di quellc Sangiulianesi, Atti d. r. Accad. d. fisiocrit. in

Siena, 1905, xvii, 601-604.
Barringer, Benjamin, S.: The 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,

— Carcinoma of Prostate, Surg., Gynec., and Obst., 1922, xxxiv, 168-176.

'Barrow, W.: Treatment of Malignant Uterine Conditions with Radium, Kentucky

Med. Jour., December, 1921, p. 770.
Sartels, C. D.: Badiumbehandlingena Stilling i Udlamlet-Hospitalistid, February 23,

1921, pp. 117-127.
Banhford, Murray, and Bowen: Third Scientific Report of Imperial Cancer Research

Fund, 1908, pp. 276 and 298.

— , — , and Cramer: Second Report Imperial Cancer Research Fund, 1905.
Baud and Mallot, L.: Universal Apparatus for Radium Therapy, Jour, do radiol et

d'electrol., June, 1921, v, 271.
Baumm, Gustav : Vorlaufige Mitteilung iiber die therapeutische Verwendbarkeit des

Mesothoriums. Berl. klin. Wchnsehr., 1911, xlviii, No. 35, p. 1594.
Eayet, A.: Die Beliandlung des Krebses mittels Radium, Strahlentherapie, iii 473-

489.
Einige Einzellieiton iiber die Anwondung 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 Radiumtherapio fiir don tiefliegenden Krebs nach dem heutigen

Stande der Wissenschaft, Str:ililentlierai)ie, 1914-1915, v. 205-215.

Becliold, H., and ZicgJer, I.: Vorstndien iiber Gicht, Biochem. Ztschr., xx, 189; 1910,
xxiv, 146.

— and — .' Radium-Emanation und Gicht, Berl. klin. Wchnsehr., 1910, xlvii. No. 16,

p. 712.
Beck, A.: Action des rayons du radium sur les nerfs peripheriques, Bull. Internat.

Acad. d. sc. de Cracovie, 1905, pp. 286-289.
Seek, 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 Radiotherapy in Apparently Hopeless Cases

of Carcinoma. Internat. Clinics, 1921, ii, 46.

Beck, Joseph C.: Further Report on the Use of Radium, the X-ray and Other Non-
Surgical Measures, Combined with Operations about the Head and Neck, Ann.
Otol. Rhinol. and Laryngol.. June. 1921, xxx, 425-496.

Beckton, H., and Suss, S.: The Effect of Radium Emanation on Altmann's Granules,
Arch. Middlesex Hospital. 1911, xxiii. 52-55.

Beclere, A.: Le dosage en radiotherapie, La Presse med., 1904, pp. 75-78.

— Note sur 1 'emploi therapeutique des sels de radium, Bull, et mem. Soc. med. d.

hop. de Paris, 1904, xxi, series 3, 1202-1215.
Nouveau precede 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 Beclere, Henri: Die radiotherapeutische Beliandlung der Leukamie, Strahlen-

therapie, 1913, iii, 553-560.
Becquerel, Henri: Sur diverses proprietes des rayons uraniques, Compt. rend. Acad. d.

sc., 1896, cxxiii, 855.
Sur le rayonnement de 1 'uranium, Compt. rend. Acad. d. sc., 1900, cxxxi, 137.

— Sur la lumiere fenise spontanement par certains sels d 'uranium, Compt. rend.

Acad. d. sc., 1904, cxxxviii, 184.

BIBLIOGRAPHY 329

Becqucrel, Paul: Recherche sur la radioactivity vegetale, Compt. rend. Acad. d. sc.,
1905, cxl, 54.

— Influence dcs sels d 'uranium et dc thorium sur Ic developpement du bacille de la

tuberculose, Semaine med., 1913, No. 4, p. 45.

Jjegmiin: Zwei Fiille von Lympliosarkom des Halses, Strahlcntherapie, 1914-1915, \,

651-654.
Radium Treatment of Uterine Cancer, Gynec. et Obst., Paris, 1921, Iv, 440.

Beirne, JI. P.: Physics and the Use of Radium, Illinois Mcd. Jour., March, 1921,
xxxix, 201.

Belot, J.: La valeur de la radiotherapie, Paris med., 1917, xxi, 445-450.

Benczur, Julius v.: Ueber einen nach Gebrauch einer Radium emanationskur wesent-
lich gebesserten Fall von Sklerodermie, Deutsch. med. Wchnschr., 1911, xxxvii,
No. 22, pp. 1029-1030.

Ueber Heilerfolge mit Radiumemanationskuren, Bcrl. klin. Wchnschr., 1912, xlix,
No. 3, pp. 108-109.

Jj<ii«likt, W.: Zur Frage der Amvendnng grosser oder kleiner Dosen von Radium-
emanation, Med. Klin., 1912, v-iii, 143-145.

Benjamin, E., llcuss, A., Slcuka, E., and Schwartz, G.: Beitrage zur Frage der Ein-
wirkung der Rontgenstnihlen auf das Blut, Wien. klin. Wchnschr., 1906, pp.
788-794.

Hennewitz: Messmethoden der Radioaktivitat und ihre Anwendung in der Radiothe-
rapie, Radium in Biol. u. Heilk., 1911, i, 121-131.

Benthin, W.: Strnhlenthcrapeiitische Einzelbeobachtungen, Monatschr. f. Geburtsh. u.
Gynak., 1921. liv, 34-39.

Berg, W. N., and Wcllter, W. H.: Experiments to Determine the Influence of Radium
Bromide on Protein Metabolism in Dogs, Science, New York, 1906, xxiii, 333.

Beraell, Peter: Ueber Radioaktivitat, Deutsch. med. Wchnsehr., 1905, No. 35, p. 1394.

— Ueber den Einfluss der Radiumsalze auf den fermentalen Eiweissabbau, Med. Klin.,

1905, i, No. 13, pp. 310-314.

• and Bickel, A.: Experimentclle Untersuchungen iiber die physiologische Bedeut-
ung der Radioaktivitat der Minerahvasser, Verhancll. d. Kong. f. inn. Med.,
1905, pp. 157-162.
Bcrgonie, J.: Le radium au point de vue medical; ce qu'on en sait et ce qu'on en

ignore, Arch, d 'electric, med., 1904, xii, 123-132.

Radium and Radiumtlierapy, Jour, de med. de Bordeaux, May 10, 1921, xcii, 255.
Radium Treatment of Roentgen Dermatitis, M^decine, Paris, June, 1921, ii, 675.
- and Spider, E.: Le traitement du cancer uterin inoperable par la Roentgentherapie

ct la Radium Therapie, Arch d 'electric, med., 1915, No. 391 pp. 140-148.
— and Tribondeau, L.: £tude experimental de 1 'action des rayons x sur les globules

rouge du sang, Compt. rend. Soc. d. biol., 1908, Ixv, 147-149.
Bernheim and Dieupart: Traitement de la tuberculose par 1'iode menthol radioactif,

Bull. gen. de therap., 1911, clxi, 868-871.
Bernstein, Sigmund: Ueber den Einfluss der Radiumemanation auf den respiratorischcn

Gaswechsel, Strahlentherapie, 1912, i, 402-410.
Bertier: Lies etuves locales radio-actives dites Berthollets a Aix les Bains, Gaz. d.

eaux, Paris, 1911, liv, 669-671.
Bertolotti, Mario: Ueber einen Fall von mit Rontgen-Radiumtherapie genheiltem

Kar/.inmn dor Tonsillen, Strahlentherapie, 1915, vi, 447-456.

Radium Therapy of Tumors of the Hypophysis with Acromcgaly, La Radiol. m€d.,

1919, vi, 315, Abstract in Arch. Radiol. and Elcctroth., January, 1921, p. 254.

Reason, Paul: Le radium et la radioactivite. Proprietes generales; emplois medicaux,

Paris, Gauthier-Villars, 1904.

Bcurman, dc: Action therapeutique du radium, Semaine med., 1907, No. 43, p. 514.
Biclcel, A.: Ueber die biologische Wirkuncr des Mcsothoriums. Emanationsvvirkung,

Berl. klin. \\Yhnschr., 1911, No. 47,' p.. 2107.
Radioaktive Stoffe und Fermente, Handb. d. Radiuml>iol. u. Therapie, von P.

Lazarus, 1912, pp. 108-119.

Beitrag zur Thorium X Behandlung des perniziosen Anamie, Berl. klin. Wchnschr.,
1912, No. 28, pp. 1322-1323.

— Weitere Beitrage zur Thorium-X-Therapie bei Anamie Leukamie und rheumat-

ischen Erkrankungen, Berl. klin. Wchnschr., 1913, No. 8, p. 346.
Mode-cm- Radium und Thorhmitherapie bei der Behandlung der Geschwiilste, der
Gicht der rheumatisclu-n Erkrankungen der Neuralgien und der Blutkrank-
heiten, Berlin, 1914, A. Hirschwald.

330 RADIUM THERAPY

— and Engclmann: Demonstration eines transportation Inhalationsapparates fur

Kadiumemanation mit kontinuierlicher regulierbarer Emanationsspeisung, Bcrl.
Win. Wchnschr., 1911, No. 10, p. 447.

— and Min-nami: Ueber die biologische Wirkung des Mesothoriums Strahlenwirkung

und Autolysc, Berl. Win. Wchnschr., 1911, No. 31, p. 1413.

Bircli-Hirsclifeld, A.: Die nervenzellen der Nctzhaut untcr physiologischen und path-
ologischen Verhaltnisse'n mit besoinlcrer Berfieksichtigung dcr Blcndung,
Munchcn. mod. Wchnschr., 1904, No. 27, pp. 1192-1195.

— Die Wirkung der Rb'ntgcn-und Badiumstrahlen auf das Auge, Arch. f. Ophth., 1904,

lix, 229-310.

Klinische und anatomische Untersuchungen iiber die Wirkung des Radiums auf die
trachomatosc Bindehaut, Klin. Monatsbl. f. Augen., 1905, xliii, Part 2, pp.
497-513.
Bissell, Joseph B.: Cancer and Radium, Internal. Jour. Surg., 1914, xxvii, 182-185.

• The Surgical Status of Radium Treatment of Cancer, Internal. Jour. Surg., Sep

tember, 1914, xxvii, 324-325.

Some Radium Therapeutics, Med. Rec,, New York, July 11, 1914, pp. 55-58.
— - The Intravenous Injection of Radium Element, The Pennsylvania Med. Jour.,
November, 1914, xviii, 129-133.

— Cancer Destruction by Radium, Siirg., Gyncc. and Obst., July, 1915, xxi, 98-102.

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332 RADIUM THERAPY

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334 RADIUM THERAPY

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441.
Czerny, Vincenz: L 'action du radium sur les tissus vivants Cong. Franc, dc ehir., 1904,

pp. 236-237.
Bemerkungon iiber die Injektion von Badiumpraparaten bci malignen Tumoren,

Deutsch. med. Wchnschr., 1909, No. 51, p. 2252.

336 RADTCM THERAPY

Ueber den Gebrauch der Fulguration und der Krouznacher Radiopraparate bei
der Behandlung des Krebse, Arch. f. klin. Chir., 1909, xc, 137-152.

• Zur Eroffnung der II, intornat. Konfcrenz fiir Krebsforschung in Paris, Miinehen.

med. Wchnschr., 1910. No. 44, pp. 2305-2307.

— and Caan, A.: TJeber die Behandlung bosartiger Gcschwiilste mit radioaktiven Sub-

stanzen, speziell mit Aktinium, Miinehen. med. Wchnschr., 1911, No. 34, pp.
1801-1802.

— • and — Ueber die Behandlung bosartiger Geschwulste mit Mesothorium und Thor-

ium X, Miinehen. med. Wchnschr., 1912, No. 14, pp. 737-742.

Czrellitzcr: Becquerelstralilen und Blindhoit, Berl. klin. Wchnschr., 1903, xl, No. 28,
p. 650.

Jtacosta, A. F. Jr.: Radium Treatment of Cancers, Brazil-med., February 5, 1921,

xxv, No. 5, p. 73.

Radium Treatment of Cancers, Brazil-med., February 19, 1921, xxv, No. 8, p. 98.
Daels, F.: Radwm Therapeutic Drainage. Gynecologic et Obstetrique, Paris, 1921,

iv, 459.

Danne: Sur un nouveau mineral radifere, Compt. rend. Acad. d. sc., 1905, cxl, 241.
Danysz, Jean: De 1 'action pathogene des rayons. 'et des emanations emis par le radium

sur differents tissus et differents organismes, Coni])t. rend. Ac:id. d. sc., 1903,

cxxxvi, 461-464.
De 1 'action du radium sur les differents tissus, Compt. rend. Acad. d.

sc., 1903, cxxxvii, 1296-1298.

— De 1 'action du radium sur le virus rabique, Ann. de 1'Inst. Pasteur, 1906, xx, 20G-

208.
Sur le ralentissement subi par les rayons B lorsqu'ils traversent la matidre, Compt.

rend. Acad. d. sc., 1912, cliv, 1502-1504.
Darier, M.: Action analgesiante du radium, Semaine med., 1903, No. 40, p. 330.

• Application therapeutique du radium dans quelques affections nerveuses, Semaine

mod., 1904, p. 51.
— , Valade, and Terson.: Traitement de 1 'epithelioma par le radium, Presse med., 1905,

No. 54, pp. 430-431.
Harms, H.: Ueber Radium und seinen Einflusz auf die Korpertemperatur des Menschen,

Inaug.-Diss., Berlin, 1911.
Darwin, C. G.: The Structure of the Atom, Nature, 1920-1921, cvi, 51-54, 81-83, 116-

118.
Dauphin, J.: Influence des rayons du radium sur le developpemenfy et la croissance des

champignons inferieurs, Compt. rend. Acad. d. sc., 1904, cxxxviii, p. 154.
Dautwitz, Fritz: Beitrag zur biologisehen Wirkung der radioaktiven uranpecherzuck-

stande aus St. Joachimsthal in Boehmen, Ztschr., f. Heilk., 190G, Abt. fur

Interne Med., pp. 81-96.

— Ueber St. Joachimsthaler Badimntrager, Wien. klin. Wchnschr., 1911, No. 22, jip.

775-777, 1912, No. 3, pp. 119-122.
David, Oskar: Emanationsapparat mit genauer Dosierung, Radium in Biol. u. Heilk.,

1913, ii, 345-352.
Davidsolm, Felix: Radiumemanation als Heilfafctor, Deutsch. med. Wchnschr., 1908,

No. 38, pp. 1633-1635.
Davidson, Mackenzie, James, and Lawson, Arnold: A Case of Spring Catarrh Treated

and Cured by Radium, Tr. Ophthal. Soc. of the United Kingdom, 1909, xxix,

239-245.

Davison, J. M.: Radium and Some of Its Physical and Therapeutic Properties, Bris-
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Denver, John B.: Hysterectomy at the Lankenau (formerly the German) Hospital,

Ann. Surg., 1921, Ixxiii, 84-90.
Debicrnf, A.: Sur une nouvelle matiere radio-active, Compt. rend. Acad. d. sc., 1899,

cxxix, 593.

• Sur un nouvel element radio-actif: 1 'actinium, Compt. rend. Acad. d. sc., 1900,

cxxx, 906.

— Sur la decomposition de 1'eau par les sels de radium, Compt. rend Acad. d. sc.,

1909, cxlviii, 703.
Deceive: Un cas d'arthrite blennorragiquc suppuree traiWe et gueric par le radium,

Jour. med. franc.-, Paris, 1910, iv, 248-252.
Deffosscs, P.: Lc Radium en therapeutique, Presse med., 1905, No. 16, pp. 121-122.

BIBLIOGRAPHY 337

Degrais, P.: Radiumbehandlung dcs Ehinophymas, Strahlentherapie, 1913, iii, 86-88.

• Cancer of the Cervix, Arch. Mens. d'Obste. et de Gynec., Paris, November, 1919,

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Radium Treatment of Vulvar Vegetations, Gynec. et Obst., Paris, 1921, iv, 493.

— and Bellot, Anselnie : Uteruskrebs und Radium, Strahlentherapie, 1914-1915, v, 102-

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• — Radium, Mesothorium und harte X-Strahlung, Leipzig, Nemnich, 1914.

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• Reports on Cancer Patients Treated with Roentgen or Radium Rays Remaining

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• Zur Strahlcnbehandlung des Krebses, Zentralbl. f. Gynak, 1915, No. 12, pp.

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— and Seuffert, von: Unsere weiteren Erfahrungen mit der Mesothoriumbehandlung
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Domarus, A., von: Weitere Beitraege zur biologisehen Wirkung des Thorium-X, Strahlen-
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— and Salle, V.: Ueber die Wirkung des Thorium X auf die Blutgerinnung, Berl.
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Dominici, Henri: Le Radium au point de vue phyjdologique ct therapcutique, Presse
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338 RADIUM THERAPY

Du traitement des tnmeurs malignes par le rayonnement ultra-penetrant du radium,
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Uebcr Radiumbehandlung, tiefliegender, inoperabler carcinome, Berl. klin.
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— Physique medicale du radium traitement des cancers par le radium, Arch. gen. d.

med., 1909, pp. 404-482.

— Des sels de Radium insolubles en therapeutique, Presse med., 1910, No. 22, p.

186-187.

— Traitement des tumours malignes par le radium, Gaz. d. hop., 1910, Ixxxiii, 1265-

1268.

— Die Rezeptivataet der normalen und pathologischen Gewebe fiir die Radium-

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Ixiv, 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-

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— , — , and Barbarin: Guerison d'un Hemo-Lymphangiome profond des regions cerv-

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— and Faure-Beaitlicu, M.: Repression d'un Sareome de la gencive par 1 'evolution Fi-

bromateuse sous 1 'influence du rayonnement ultra penetrant du Radium,
Presse med. 1909, xvii, 77-79.

— and - Arret et sejour prolonge du sulfate de radium dans les tissus vivants, pen-

dant une duree excedant une annee, Compt. rend. Soc. de biol., 1910, Ixviii,
46-48.

— Harct, P., and Jaboin, A.: Sur les modifications des tissus consecutives a 1 'introduc-

tion du radium par electrolyse dans 1'organisme vivant, Compt. rend. Soc. de
biol., 1911, Ixx, 431-432.

— Laborde, A., and Laborde, Mme, A.: De la Fixation, par le squelette, au radium

injeete a I'eiat soluble, Compt. rend. Soc. de biol., 1913, Ixxv, 108-110.

— and Martel, de : Radiumtherapie du cancer de la langue, Presse med., 1910, No. 18,

p. 155.

— , Petit, G., and Jaboin, A.: Sur le radioactivity persistante de 1'organisme resultant
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, — j and — Radioactivite persistante de 1'organisme sous 1 'influence des injections

du radium insoluble. Serotherapie radioactive, Comp. rend. Acad. d. sc., 1911,
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— and Rubens, Duval: Sur le processus Histologique de la Destruction des Cellules

Epithelioma tenses, par le Rayonnement Ultra-Penetrant du Radium, Bull. et.
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— and Warden, A. A.: The Technique and Results of Radium Therapy in Malignant

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of Malignant Disease and of Estimating Suitable Dosages, Boston Med. and

Surg. Jour., December 6, 1917, elxxvii, 787-799.

— and Greenough, Robert B.: Report of Results of Radium Treatment at the Collis P.

Huntington Memorial Hospital by the Cancer Commission of Harvard Uni-
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DuCasKe, B. B.: Radium and Hypertrichosis, Observations and Technic, Radium, Sep-
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Duncan, Hex: Recent Developments in Radiumtherapy, California State Jour, of Med.,

March, 1921, xix, 102-105.

Superficial Epitheliomata with Results and Observations in the Treatment of
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und Sieveking, Physik. Ztschr., 1916, xvii, 73-76.

340 RADll'M THERAPY

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Erskine, A. W.: The Use of X-rays and Kadium in the Treatment of Certain Non-
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Bericht iiber die bishcr gemachten Erfahrungen, bei der Rohandlung von Carcinomen
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Demonstration von einem Fall von Karzinom des Mundes und einem Fall von
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Exner, Sigm: Einige Beobachtungen ueber die durch Radiumstrahlen in den thierischen
Geweben crzeugte Phosphorescenz, Zentralbl. f. Physiol., 1903, xvii, 177-179.

Fabcr, Alexander: Einwirkung der Rontgenstrahlen auf die Sexualorgane von Thier

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1911, Ixx, 419-420.
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d. med., 1910, pp. 81-87.

— and Fabre, M. G.: Technique et outillage actuals en Radiumtherapie, Arch, d 'elec-

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— and Touchard, Paul: Traitement de la syringomyelie par le radium, Progres med.,

1909, xxv, 648-653.

Failla, Gioacchino: Radium Technique at the Memorial Hospital, New York, Arch.
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— Absorption of Radium Radiations by Tissues, Am. Jour. Roentgen ology, May, 1921,

viii, 215-231.

— The Physical Basis of Radium Therapy, Arch. Dermat. and Syph., 1921, iii,

133-141.

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— , — , and Zarzycki: Ueber die Wirkung von induzierter Radioaktivitat, Wien. klin.

Wchnschr., 1913, No. 3, pp. 94-95.

— , — , and - Ueber Wirkung von Polonium, Strahlentlierapie, 1913, iii, 333-342.
Ferreri, Gherardo: Le radium dans la therapeutique laryngologique, Arch, internal.

de laryngl., 1907, xxiv, 730-736.
Field, C. Everett: Radium — Its Physiochemical Properties Considered with Relation to

High Blood Pressure, Med. Rec., New York, 1916, Ixxxix, 135-139.

• General Practitioner's Interest in Radium, New Jersey Med. Soc. Jour., January,

1921, xviii, No. 1, p. 15.

Findley, Palmer: Radium Treatment of Cancer of the Cervix, Am. Jour. Surg., Novem-
ber, 1916, xxx, No. 11, pp. 337-339.

Finzi, N. S.: Inoperable Recurrent Carcinoma of the Breast Under Treatment by
Radium, Proc. Roy. Soc. Med., Clinical Section, ii, 226-227.

• Sarcoma of the Ear and Mastoid Region Under Radium Treatment, Proc. Roy.

Soe. Med., Clinical Section, 1910, iii, 157-159.

• A Case of Oesophageal Growth Under Treatment by Radium, Proc. Roy. Soc. Med.,

Clinical Section, 1910, iii, 160-162.
The Radium Treatment of Cancer; Experiences of over 100 Cases, Lancet, London,

1911, clxxx, 1339-1344.

Radium Therapeutics, London, 1913, Oxford University Press.
Le Traitement des Tumeurs par le Radium ct les Rayons X, Jour, de radiol. et

d'electrol., 1920, iv, No. 11, pp. 491-502.

— and Hill, W.: Malignant Growth in Neck Treated with Radium, with Recurrence in

Mediastinum, Proc. Roy. Soc. Med., Clinical Section, 1910, iii, 159-160.
Fiorini and Zironi, A.: Immunicorps et Rayons Rontgen, Arch, d 'electric, med., 1914,

pp. 113-116.
Fislicr, Carl: Epithelioma of the Lids, Jour. Am. Med. Assn., August 29, 1914, Ixiii,

751-755.
Fidchncr, Otto: The Action of B-rays on Photosensitive Solutions, Jour. Chem. Soc.,

1909, xcv, 327-331.
Flalau: Vorlaufige Ergebnisse der Strahlenbehandlung des Geljarmutterkrebses, Strahl-

entherapie, 1916, vii, 289-299.
Flemminri : Experimcntelle und klinische Studien fiber den Heilwert radioaktiver

Strahlen bei Augenerkrankungen, von Graefe's Arch. f. Ophth., 1913, Ixxxiv,

345-400.
Radium und Mesothorium in der Ophthalmologie, Strahlentherapie, 1914, iv, 681-

707.

342 RADIUM THERAPY

— and Kntsius : Zur Einwirkung ' ' strahlender Encrgie ' ' auf die experimentelle Tuber-

kulose des Auges, Deutsch. mod. Wchnschr., Kill, xxxvii, 1600.

— and, — Radiumtherapie bci Augenerkrankungen, Charite-Ann., 1911, xxxv, 503-510.
Floyd, W. 0.: X-ray :ind Radium as an Aid to Surgery in Deep Seated Malignancies,

Southern Med. Jour., September, 1921, xiv, 697-703.
Fofanow, Leo: Ueber den Einfluss der Radiumemanntion auf das Mononatriumurat im

tierisehen Organismus,' Ztsclir. f. klin. Mod., 1910, Ixxi, 322-337.
Fonck, Franz: Radium nnd Nervensystem, Leipzig, 1906, G. Thieme.
Foote, Edward M.: The Place of Radium in Surgery, Ann. Surg., March, 1917, Ixv,

273-281.
Forsell, G.: Quelques observations de radiumtherapie des tumeurs eancereuses, Ztschr.

f. Roentgen, u. Radiumfortsch., 1911, xiii, 28-29.
Foveau dc Courmelles: Le radium en therapcutiquc nervcuse, Semaine med., 1904, No.

32, p. 255.

— Die RSntgen- und Radiumstrahlen in der Gyniikologie, Strahlentherapie, 1913, iii,

388-407.

Fraga, E.: Radioaktivitiit der Heilquellen Chiles, Leipzig, 1912, Thieme.
Frank, Robert T.: The Palliative Treatment of Inoperable Carcinoma of the Cervix

by Means of Radium, Jour. Cancer Research, January, 1917, ii, 85-102.
Franke, M.: Ueber den Einfluss der Rocntgenstrahlen auf den Verlauf der Leukamie,

Wien. klin. Wchnschr., 1905, No. 33, pp. 857-864.
Frdnkel, Ernst: Thorium X-Trinkkuren in der Praxis, Ztschr. f. Rontgenk. u. Radium-

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— and Gumperts, Fricdrifli: Ueber die Einwirkung von Thorium X-Injektionen auf

die Agglutinine, Berl. klin. Wchnschr., 1914, No. 5, pp. 209-210.

FranJcenluhiser : Unsere Wildbader und ihre Wirkung, Ztschr. f. Balneol., 1908, i,

411-417.

Frdnkl, 0., and Amrcich, I.: The Histological Changes Incident to Radium and X-ray

Treatment of Uterine Carcinoma, Surg., Gynec, and Obst., August, 1921,

xxxiii, 162-163.

Franklin, Walter S., and Cordes, Frederick C.: Radium for Cataract, Am. Jour.

Ophth., September, 1920, pp. 643-047.

— and — Radium Applicator for Cataracts, Am. Jour. Ophth., June, 1921, iv, Series

3, No. 6, pp. 429-430.
Freer, 0. 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.
Freudenthal, Wolff A.: A Case of Lcukoplakia Treated by Radium, Arch. Physiol.

Therapy, 1906, iv, 7-9.

— Experiences with Radium in Diseases of the Throat and Noso, Jour. Advanc.

Therap., 1906, xxiv, 279-287.

— Ueber die Behandlung maligner Tumoren der oberen Luftwege mittelst Radium,

Arch. f. Laryngol. u. Rhinol., 1911, xxv, 3-8.

Freund, Ernst, and Kumincr, Gisa: Ueber chemist-he AVirkungen von Rb'ntgen- und
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— and Kriser, Arthur: Ueber die Behandlung der Ischias, Tabes und chronischen

Gelenkkrankheiten mit Mesothorschlamm, Therap. Monatsh., 1913, xxvii, 282-

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Freund, Prof. Hermann: Intraperitoneale Verwendung von Radium, Deutsch med.

Wchnschr., 1914, xl, 1252-1254.
Freund, Leopold: Grundriss der gesammten Radiotherapie fiir praktische Aerzte, Berlin

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Versuche mit Radiolymphe, Fortschr. a. d. Geb. d. Rontgenstrahlen, 1913, xxi, No.

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Friedel, C. and Cummcngc, E.: Sur un nouveau mineral d'urane la caruotite, Compt.

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Friedlander, W.: Ueber lokale Mesothoriumtherapie, Berl. klin. Wchnschr., 1912, No.

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Fukuda, H.: Treatment by Radium Ray, Abstracted in Jour. Am. Med. Assn., August

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Funke: Einwirkung von Radium auf maligne Tumoren, Yerhandl. d. deutsch. Gellsch.

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Fvrniss, S. D.: Simple Method to Retain Radium in Cervix and Uterus, Jour. Am.

Med. Assn., 1921, p. 623.

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344 RADIUM THERAPY

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346 RADIUM THERAPY

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Harris, T. J.: Radium in Cancer of Larynx with Particular Reference to Dosage and
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350 RADIUM THERAPY

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352 RADIUM THERAPY

Ketron, L. W.: Quoted by Seil, Viol and Gordon, New York Med. Jour., 1915, ci, 896-

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Kin-liner, Huns: TJeber die kosmotischen Vorziige der Heilung von Lidkrebsen duivh

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Kirkendall, B. It.: Radium in Treatment of Carcinoma of Breast as Adjunct to Sur-
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— and Diirck, II.: Mikroskopische Befunde an Karzinomen nach Mesothorbestrahlung,
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Klempercr, d., and Hirschfeld: Der Jetzige Stand der Thorium-X-Therapie mit eigen
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— Weitere Mitteilungen iiber die Beliandlung der Blutkrankheiten mit Thorium-X,

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354 RADIUM THERAPY

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BIBLIOGRAPHY 355

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356 RADIUM THERAPY

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i, 256-266; ibid., 1913, ii, 9-19.
Radiunitlierapio in der Zahnheilkundc, Strahlentherapie, 1914, iv, 123-133.

Lewin, Carl: Die Radiumbehandlung innerer Geschwiilste, Verhandl. d. deutsch, Kongr.
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• Zur Radiumtherapie dcs Oesophagus- und kardiacarcinoms, Therap. d. Gegenw.,

1914, pp. 103-110.

Lewis, E. T.: Disappearance of Mediastinal Neoplasm Under Roentgen Ray and Ra-
dium Treatment, Lancet, London, November 27, 1920, ii, 1092.

Lewis, W. II.: Radium Service in Harbin Hospital from February 1 to December 1,
1920, Jour. Med. Assn. Georgia, May, 1921, x, 417.

Licit, Charles, W.: The Nauheim Treatment as Given at the Glen Springs, Canad.
Pract. and Rev., 1910, xli, 145-154.

Liebcr, Hugo: A New and Possibly Improved Method of Using Radium, Arch. Ront-

gen. Ray, 1905, ix, 253-255.
Das Radiumkleid, Therap. Monatsch., 1905, xix, 318-319.

Linmrt, Gerliard: Experimentelle und klinische Untersuchungen iiber die Wirkung
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Linscr, P., and Helber: Experimentelle Untersuchungen iiber die Einwirkung der
Rontgenstrahlen auf das Blut und Bemerkungen uber die Einwirkung von
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— and Sick, K.: Ueber das Verhalten der Harnsaure und: Purinbasen im Urin und

Blut bei Rontgenbestrahlungen, Deutsch. Arch. f. klin. Med., 1907, Ixxxix,

413-431.
Lobenhoffer, W.: Erfahrungen mit Mesothoriumbehandlung maligner Tumoren, Beitr.

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Loeb, L. B.: The Fundamental Physical Action Underlying the Physiological Action

of Radium Rays, X-rays and Ultra-violet Light, Jour. Radiol., July, 1921,

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Locu-enthal, S.: Ueber die Wirkung der Radium-emanation auf den menschlichen

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— Ueber die Einwirkung von Radiumemanation auf Neubildungen, Berl. klin.

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Demonstrationen zur Emanationstherapie, Med. Klin., 1910, vi, No. 16, p. 629.
— - Ueber die Wirkung der Radiumemanation auf den Menschen, Berl. klin. Wchnschr.,
1910, No. 7, pp. 287-291.

Ueber Meszmethoden und Einheiten in der Biologischen Radiumforschung, Physik.
Ztschr., 1911, xii, 143-147.

Ueber die Indikationen der Radiumtherapie bei inneren Krankheiten, Strahlen-
therapie, 1912, i, 12-16.

• Grundriss der Radium therapie und der Biologischen Radiumforschung, unter Mit-

wirkung von F. Gudzent, A. Sticker, und E. Schiff, Wiesb., 1912, J. F. Berg-
mann.
• — and Edelsiein, E.: Ueber die Beeinflussung der Autolyse dureh Radiumemanation,

Bioch'em. Ztschr., 1908, xiv, 484-490.
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des diastatischcn Fermentes, Biochem. Ztschr., 1909, xxi, 476-483.

Loewy, A. : Versucho iiber die Wirkung der Radiumemanation auf das Blutgcfass sys-
tem, Berl. klin. Wchnschr., 1912, No. 3, pp. 109-113.

— and PlescJi, J.: Ueber den Einfluss der Radiumemanation auf den Gaswechsel und
die Blutzirkulation des Menschen, Berl. klin. Wchnschr., 1911, No. 14, 606-
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Lohe, H.: Toxikologische Beobachtungen uber Thorium-X bei Menseh und Tier,

Virchows Arch., 1912, ccix, Nos. 1 and 2, pp. 156-167.
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Uber das Verhalten der Radiumstralilen auf dem Gebiete des Sehens, von Graefe's
Arch. f. Ophthal., 1903, Ivii, 342-302.

358 RADIUM THERAPY

Weitere Untcrsuchungen iiber Radhumvirkung, Berl. klin. Wclmschr., 1905, No.
42, pp. 1336-1338.

— Das Radium in der Biologic und Medizin, Leipzig, Akad., Verlagsgescllsch, 1911.

— and Goldberg, S. W. : Zur Frage der Beziehungen zwisehen Becquerelatrahlen und

Hautaffektioncn, Dermat. Ztschr., 1903, x, 457-462.
Lessen, J.: Die biologischen Wirkungcn der Rbntgen-und Becqucrelstrahlen, Berlin and

Wien, 1917, Urban and Schwarzenberg.
Lusby, S. G.: Some Experiments on lonization in Dried Air, Proc. Cambridge

Philosophical Soc., 1910, xv, 459-404.
Lynch, Fran].; ]V.: The Problem of Uterine Cancer, California State Jour. Med., 1920,

xviii, 47-49.
Lyster, C. B. C., and Kuss, S.: The Clinical Use of the Active Deposit of Kaclium,

Proc. Roy. Soc. Mod., Electro-therapeutics Section, 1912, v, 150-154.

Maclntyre, John: Radium and Its Therapeutic Kfl'ects, Brit. Med. Jour., December,
1903, pp. 1524-1526.

MacKce, George M.: Progress in the Treatment of Skin Diseases, New York Med.

Jour., March 4, 1916, ciii, 441-444.

— and Andrews, G. C.: Roentgen Dermatitis and Radium Dermatitis; a Comparison,
Arch. Dermat. and Syph., August, 1921, iv, 213-216.

• — and — Injurious Combined Effect of Roentgen Rays or Radium and Topical Reme-
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McCoy, Herbert N.: Ueber das Entstehen cles Radiums, Ber. deutsch. Chem. Ges., 1904,
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— The Relation Between the Radioactivity and the Composition of Uranium Com-

pounds, Philosophical Mag., 1906, xi, Series 6, pp. 176-186.
McCruddcn, F. H.: Influence of Radium Water Therapy on Creatinm and Uric Acid

Metabolism in Chronic Arthritis, Am. Jour. Med., November, 1918, clvi, 702-

705
McCurdy, J. R. : Advanced Epithelioma of Lower Lip, Radium, June, 1915, v, No. 3,

pp. 64-66.
Maass, Th., and Plesch, J.: Wirkung cles Tliorium-X auf die Circulation, Ztschr. f.

exper. Path. u. Therap., 1912, 1913, xii, 85-94.

Maclie, Heinrirlc: Ueber die Radioaktivitat der Thermen von Wildbadgastien, Wien.
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- and Meyer, Stefan: Ueber die Hsidioaktivitat der quellen der bohmischen Biider-

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_ and — Ueber Radiumnormale, Physik. Ztschr., 1912, xiii, 320-322.

Mackenzie, Kenneth A. J.: Personal Experiences with Radium in Treatment of Can-
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Mal-oiver, W.: The Molecular Weights of Radium and Thorium Emanations, Philo
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— and Fajans, K.: The Growth of Radium C from Radium B, Philosophical Mag.,

1912, xxiii, 292-301.

- and Geiger. H.: Practical Measurements in Radioactivity, London, 1912, Long-

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— and Moseley, H. G. G.: Gamma Radiations from Radium B, Philosophical Mag., 1912,

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Mandel, H.: Arthritis nrica unter Radiumemanation, Radium in Biol. u. Hcilk., 1911,

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Manders, Horace: The Relief of Rheumatic Pains by Thorium Salts, Arch. Roentg.

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— • Die Messung von Thorium X Lo'sungon, Radium in Biol. u. Heilk., 1913, ii, 161-

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060 RADIUM THERAPY

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362 RADIUM THERAPY

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• — Soins a donner aux appareils a radium, Lyon M6d., May 10, 1921, No. 9, pp.

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— and Falta, W.: Klinische Beobachtungen iiber die physiologisehc und therapeutische

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BIBLIOGRAPHY 363

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364 RADIUM THERAPY

Ueber die Strahlenbehandlung bosartiger Geschwiilsto, Arch. f. klin. Chir., July

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Petit, G.: Radioactive Therapeutics, Presse m£d., March 12, 1921, xxix, 201.
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Radium Combined with Roentgen-Ray Treatment in Carcinoma of Breast, Am.

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Ffciffcr, II., and Friedbergcr, E.: Ueber die bakterientodtcnde Wirkung der Radium-

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BIBLIOGRAPHY 365

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Prado Tagle, E.: Ueber Gewebsveranderungen nach aubcutanen Depots von Bleisalz-
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— The Intravenous Injection of Soluble Rndiuin Salts III, Radium, March, 1914, ii,

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366 RADIUM THERAPY

The Influence of Intravenous Injection of Soluble Radium Salts on High Blood
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Pusey, William Allen: Radium in Cutaneous Lesions, Pennsylvania Med. Jour., No-
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Quick, Douglas: The Combination of Radium and the X-ray in Certain Types of Car-
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Radium Technique in Treatment of Malignant Diseases of the Skin, Arch. Der-
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Quigley, D. T.: The Relation of Radium to Surgery, Med. Herald, 1915, xxxiv, 5-9.
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— The Technique of Radium Application, Minnesota Med., March, 1919, ii, 97-99.
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— Radium Emanation (Niton) in the Bath Waters, Brit. Med. Jour., March 16,

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- and - The Chemical Action of Radium Emanation. Part III. On Water and

Certain Gases, Jour. Chem. Soc., 1908, xcii, 966-992.

— and — The Chemical Action of Radium Emanation. Part IV. On Water, Jour.

Chem. Soc., 1908, xciii, 992-997.

— and Collie, J. N.: The Spectrum of the Radium Emanation, Proc. Roy. Soc., Lon-
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- and Soddy, F.: Gases Occluded by Radium Bromide, Nature, July, 16, 1903, Ixviii,

— and — • Experiments in Radioactivity, and the Production of Helium from Radium,

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BIBLIOGRAPHY 367

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• The Technique of Applying Radium in the Various Types of Cancer of the Cer-

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— and - Radium Treatment of Leukemia, Bull. Acad de med., Paris, February 15,

1921, Ixxxv, No. 7, p. 207.

368 RADIUM THERAPY

— , — , and DesbmiiS: Badiumtherapie de la leucAnie myeloide, Bull, et mem. Soc. med.

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— , — , and Tonrnemelle: Badium versus Bontgen Bay Treatment in Splenomyelogen-

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— and Marie: Essai critique sur la radiumtherapie des infections aigues par les in-

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Repin: Badioactivite de certaines sources goitrigenes, Compt. rend. Acad. d. sc., 1908,
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— Nouvelles recherches sur la radioactivity des sources goitrigenes, Compt. rend.

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Jlheinboldt, M.: Zur baktericiden Wirkung radioaktiven Mineralwassers, Berl. klin.

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Ribardeau-Dumas and Weil, Albert: Zur un cas d 'hypertrophie du Thymus traitee par

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Richards, A.: Becent Studies on the Biological Effects of Eadio-activity, Science,

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Richards, Theodore W., and Lembert, M. E. : The Atomic Weight of Lead of Eadio-

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370 RADIUM THERAPY

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372 RADKTM THERAPY

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Sictel, Gerald: A Case of Rodent Ulcer Treated with Radium, Brit. Med. Jour., Jan-
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Kiegel, P. W.: Dauererfolge in der gynakologisehen Radiotherapie, Strahlentherapie,

1912, i, 457-476.

Siev eking, "B..: Die Radioaktivitat der Mineralquellen, Berl. klin. Wchnschr., 1906, No.

23, pp. 779-780.

Ueber Quellenmessung, Strahlentherapie, 1913, iii, 741-744.
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Gaswechsel der Menschen, Berl. klin. Wchnschr., 1908, No. 1, pp. 13-14.
Ueber den Einfluss von Radiumemanation auf den Gesamtstoffwcchsel des Menschen,

Berl. klin. Wehnschr., 1909, No. 26, pp. 1205-1206.
Silva Mello, A. da: Ueber die Wirkung der Stralilenden Encrgie auf das Blut und die

Blutbildenden Organe, StraUenthetapie, 1915, vi, 387-397.
Simmons, Clutrmiim-f/ C. : The Treatment of Carcinoma of the Skin with Radium. The

Results of the Cases Treated at the Collis P. Huntington Memorial Hospital,

Boston Med. and Surg. Jour., 1919, clxxxi, 477-483.
Simmonds, M.: Ueber Mesothoriumschadigung des Hodens, Deutsch. mod. Wchnschr.,

xxxix, No. 47, pp. 2291-2292.
SimonsoTi; S.: Die schmerzstillende Wirkung der Riintgen- und Radiumstrahlen,

Strahlentherapie, 1913, ii, 192-223.
Simpson, C. Angtistiis: The Relative Value of Radium and X-ray in Treatment of

Skin Diseases and Cancer, South. Med. Jour., October, 1914, pp. 818-821.
The Effects of Radium and X-ray on Cancer; Especially Skin Lesions of the

Disease, Virginia Med. Month., .Tune, 1921, xlviii, 155-156.

— Radium and X-ray Treatment of Hyperthyroidism, New York Med. Jour., July

6, 1921, cxiv, No. 1, pp. 36-38.
Simpson, C. Augustus: Atrophy of Lymphatic and Tonsillar Tissue by Radium and

X-Ray, Jour. Radiology, 1921, ii, 35-3S.
Simpson, Frank Edward: Radium in Skin Diseases, Jour. Am. Med. Assn., July 12,

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— Radium as a Unique Agent in Dermatologic Therapeutics, Chicago Med. Recorder,

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Radium in the Treatment of Blastomycosis, Jour. Am. Med. Assn., March 14,

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Radium — Its Use and Limitations in Skin Diseases, Jour. Am. Med. Assn., August

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374 RADIUM THERAPY

Radium in the Treatment of Lymphangioma Circumscriptum, Jour. Am. Med. Assn.,
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Radium Therapy — Remarks on the Use of Radium in Deep-seated Malignant Dis-
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Radium in the Treatment of Cancer and Various Other Diseases of the Skin, Jour.
Am. Med. Assn., November 18, 1916, Ixvii, 1508-1511.

Radium Therapy — Remarks on the Present Status of Radium in Its Relation to
Various Diseases, Especially Cancer, Radium Quarterly, January, 1917.

Radium in the Treatment of Chronic Lymphatic Leukemia, Radium Quarterly,
January, 1917.

Radium Therapy with Special Reference to the Use of Radium in Dermatology,
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— Radium in Malignant Disease, Surg. Clin., Chicago, February, 1919, iii, No. 1,

pp. 63-73.

Radium Therapy, Oxford Surgery, Sec. 14, v, 401-448.
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iv, 482.

Radium Treatment of Uterine Fibroma s, Gynec. et Obst., Paris, 1921, iv, p. 427.
Skeel, Roland E.: The Early Diagnosis and Treatment of Cancer of the Cervix. Calif.

State J. M. November, 1921, p. 438.
Sittemfifld, M. J.: The Significance of the Lymphocyte in Immunity to Cancer, Jour.

Cancer Research, April, 1917, ii, 151-157.
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Sluys, F.: Ein Fall von Makrocheilie, Strahlentherapie, 1914-1915, pp. 241-243.
Hmith, Bcllingiuim E. : The Distribution and Excretion of Radium and Its Emanation

after Internal Administration, Quart. Jour. Med., 1912. v, 249-264.
Smith, Harmon: Papilloma of the Larynx, Jour. Am. Med. Assn., December 19, 1914,

Ixiii, No. 25, pp. 2207-2211.
Smith, Jt. L.: X-ray, Radium and Surgery in Treatment of Cancer, Nebraska Med.

Jo\ir., September, 1921, vi, 282.
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Sobotky, Irving: Radium Treatment of Tinnitus and Middle Ear Deafness, New York

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Soddy, Frederick: A Method of Applying the Rays from Radium and Thorium to the

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— The Chemistry of the Radio-elements, London, 1911-1914, Longmans, Green and

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— The Interpretation of Radium and the Structure of the Atom, 1920, Putnam's

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— and Eussell, A. S.: The Gamma Rays of Uranium and Radium, Philosophical Mag.,

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Solilern: Ueber die Gicht und die Kissinger Trinkkur, Med. Klin., 1910, vi, No. 12,
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Soiland, Albert: Further Comments on Radioactivity, Am. Jour. Roentgenology, Feb-
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• An Interesting Case, Urol. and Cutan. Rev., February, 1920, xxiv, 103-104.

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— Therapeutic Aspect of Irradiation in Superficial Malignancy, Jour. Am. Med.

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— Present Status of Radium Therapy in Female Pelvis, Jour. Radiology, January,

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376 RADIUM THERAPY

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Stoklasa, 3., and Zdobnicky, V.: Influence des emanations radioactives sur la vegeta-
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378 RADIUM THERAPY

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— A Case of Myeloma of the Sternum Treated by Radium, Brit. Med. Jour., August,

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BIBLIOGRAPHY 379

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380 RADIUM THERAPY

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382 RADIUM THERAPY

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INDEX

Absorption (see Coefficient of absorption)
Absorption of alpha rays, 43, 45, 70
beta rays, 43, 45, 47, 70
gamma rays, 43, 44, 46, 70

in water, 49-68

radiation in apparatus, 129-133
in tissues, 133, 134
method of calculating, 129-134
radium emanation, by various gub

stances, 24, 25
selective, 104

Acanthosis nigricans, treatment of, 294
Acne, treatment of, 295
Actinium, discovery of, 18

emanation, 20

Actinium series, atomic weights of, 20
period of decay, 20
radiation from, 20

Actinomycosis, treatment of, 240, 286
Alopecia, as result of radiation, 295, 296
Alpha rays, absorption of, 43, 45, 70
coloration effects due to, 72
effect on blood cells, 82
fluorescence, caused by, 71
ionizing effect of, 69
properties of, 40
secondary radiation from, 44
source of, 26
therapeutic effects of, 88
Altmann's granules, 88
Amenorrhea, due to radium treatment,

242

Ampoules, emanation, described, 112, 113
instrument for inserting, 113, 153, 156
use in treatment of carcinoma, 107, 198,

202, 203

of epithelioma, 160, 188, 189
of tumors, 144, 145, 156, 157
Anemia, pernicious, treatment for, 320
Angiomata, treatment of, cutaneous, flat,

deep, 89, 111, 258 280
superficial 273
raised, hard 274

soft or cutaneous 274
subcutaneous 274-280
submucous 274-280
technic 273-280

Angiosarcoma, treatment of, 270
Apparatus, therapeutic, containing ra-
dium emanation, 109-115
ampoules or bare tubes, 112, 113
needles, 113, 114
tubes, 112, 113
containing radium salts, needles, 109,

110
plaques, 110, 111

Apparatus, containing — Cont'd

tubes, 109
for use of radioactive deposit, on

metals, 114
on wire, 114, 115
solution 115

various types of, effects, 124 128
Applicator, (see Apparatus, therapeutic)
Arthritis deformans, treatment of, 313,

319

Auditory canal, treatment of affections of,
298

Bacteria, effects of radium rays on, 73, 74
Bare tubes (see Ampoules)
Barium, associated with radium, 22
Baths, radium emanation, 311
Beta rays, absorption of, 43, 45, 47, 70
effects on tumors, 90, 91, 92
ionizing effect of, 69, 118
properties of, 41
screens for, 88
secondary radiation from, 44
therapeutic use of, 88
Birthmarks (gee Nevus)
Bladder, carcinoma of, treatment, 211,

212

Blastomycosis, treatment of, 286
Blood coagulation of, 82

effect of radium rays on, 80-82, 316-

318

thorium X on, 316, 318
Blood pressure, effect of radium treat-
ment on, 314, 320
Blood vessels, effect of radium rays on,

82, 96

thorium X on, 316

Bone, sarcoma of, treatment, 236, 237
Bone marrow, effects of radium rays on,

80, 86, 87
Brain, effect of radium rays on, 85

tumors of, 233

Breast, carcinoma of, treatment, 212-221
Bright 's disease, treatment of, 320

Cancer, effect of radium rays on, 90-102
(see also Carcinoma, Epithe-
lioma)
Carcinoma, effect of radium rays on, 87,

90-102, 158-227

treatment for, of bladder, 211, 212
of breast, 212-221
of cervical glands, 202, 203
of cervix uteri, 94, 150, 151, 221-227

385

386

INDEX

Carcinoma, treatment — Cont 'd

of esophagus, 205, 206

of fundus uteri, 226

of inferior maxilla, 199-202

of intestines, 206

of larynx, 204, 205

of lingual, bucral and pharyngeal mu-
cous membranes, 189

of mouth, 189, 199

of ovary, teratoid, 228

of penis, 208

of prostate gland, 209, 211

of rectum, 207, 208

of stomach, 206

of superior maxilla, 199

of testes, 228

of thyroid gland, 203

of tongue, 198

of tonsil, 198, 199

of urethra, 208

of uterus, 94. 150-151, 221-227

of vulva, 208

Carnotite, composition of, 21
deposits of, 21
discovery of, 21

Cartilage, effect of radium rays on, 83
Cataract, treatment of, 297-298
Cells, malignant, effect of radium rays on,

79, 80, 90, 102, 104, 145, 158-
160

normal, action of radium rays on, 77-

80, 86-87, 104, 108, 145
stimulation of, by radium rays, 80, 93,

96, 98, 99

Cervical glands, carcinoma of, treatment,
202, 203

Cervix uteri, carcinoma, of, treatment, 94,
150, 151, 221 227

Coagulation of blood, as affected by ra-
dium. 82
thorium X, 82

Coefficient of absorption, of beta rays, 118
of gamma ravs, 118, 138
of x-rays, 138

Conglutinal giant cells, 96

Contractures, 188

Cosmetic applications of radium, 106, 111,
245, 246

Orookes tube rays, 41

Curie, unit of radium emanation, 24
D

Darier's disease, treatment of, 294

Deafness, treatment of, 298

Debierne-Duane-Failla apparatus for ra-
dium emanation, 29, 35

Decay (see Bndium, Radium emanation
and Radioactive deposit)

Delta rays, 44

Dental modeling compound, 149, 189

Dermatitis, following radium treatment,

105
papillaris 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 rays, deep effects, 129,
130, 133139, 149, 152, 154,
155, 161

duration of exposure, 140-141, 143-
144, 155

for children, 117

frequency 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

Ear, (see Auditory Canal)

Ectropion, 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 (gee Radium emanation)
thorium, 20

Kndometritis, 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
Erythrocytes, as affected by 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
Eye, effects of radium rays on, 85, 86
Eyeball, phosphorescence produced in, 8S
protection of, 147

Failla machine for cutting glass tubes,

113

method of distinguishing tubes, 112
modification of apparatus for prepara-
tion of radium emanation, 29
technic for inserting emanation am-
poules, 156

INDEX

387

Ferments, effects of radium rays on, 86
Fibromyoma of uterus, treatment of, 241

244

Filters (see Screens)
Filtration of rays, 45
Finsen light, for lupus vulgaris, 285
Fluorescence, due to alpha rays, 71
Forceps, for handling radium tubes, 147,

148, 323, 324
Simpson, 148, 324

' ' Fordyce 's disease, ' ' treatment of, 283
Freer apparatus for treatment of larynx,

205, 300-302
Freer needle holder, 153, 204, 211

Gamma rays, absorption of, 43-44, 46, 70

in water, 49-68

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

penetrability of, 70

properties of, 41, 42

screens for, 46, 70, 88, 117, 118

secondary radiation from, 44
Goiter, treatment of, 83, 308, 309
Gout, treatment of, 319

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, 300

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
Hyperidrosis, treatment of, 295
Hypertrichosis, treatment of, 295
Hypertrophies, skin, treatment of, 294

tonsil, treatment of, 302

Idiosyncrasies, individual sensitiveness to

radiations, 108

Immunity, produced by radiation, 99-102
Inflammation, due to radium rays, 75, 88,

103-105, 149, 245, 322
Inhalation of radium emanation, 311, 319
Injuries, professional, due to radium, 322-

324
Insufficient radiation, stimulation due to,

98, 99

Intensity of gamma 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
International Eadium Standard, 36
Intestines, carcinoma of, treatment, 206
Intratumoral radiations, 107 , 144, 140,

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
Joly and Stevenson, steel needles, 113

Keloids, treatment of, 246-257
Keratosis, treatment of, 294
Kidneys, effect 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 rays on, 81,

304, 316

thorium X on, 316
observation of, during treatment, 102
Leukemia, radioactive deposit treatment,

320

radium ray treatment, 81, 303-308
lymphatic, 304, 305
myelogenous, 303, 304
technic of, 306, 307
Leukemia cutis, treatment of, 294
Leukopenia, brought on by exposure to

radium rays, 323

Leukoplakia, treatment of, 189,198
Lichen chronicus simplex, treatment of,

286, 289

Lichen planus, treatment of, 288
Liver, effects of radium rays on, 84
Lupus erythematosus, treatment of, 287-

294

Lupus vulgaris, treatment of, 282 284, 286
Lymphadenoma (fee Hodgkin's disease)
Lymphangiomata, treatment with radium

rays, 258, 275, 281

Lymphatic glands, effects of radium rays
on, 80, 86, 87

388

INDEX

Lymphosarcoma, radioactive deposit treat-
ment, 320
radium ray treatment, 230, 238, 239

Malignant cells, effect of radium rays on,
79, 80, 90-102, 104, 145

Maxilla, inferior, carcinoma of, treatment,

199-202
superior, carcinoma of, treatment 190

Melanosarcoma, treatment of, 229

Menopause, due to radium treatment, 241,

243
due to x-ray treatment, 242

Menorrhagia, treatment of, 244

Mesothorium, discovery 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-
activity, 72

Microcurie, defined, 36

Millicurie, a unit of measurement, 36

Millieurie 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

Xails, 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, 145,

155, 156
Nervous 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, 259

280

linear, 279, 283

pigmentosus, 268, 269, 276-278, 281
vascular, 266
Niton, 24
Noble gases, 24
Nose, sarcoma of, treatment, 188

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
Pitchblende, 21
Plaques, radium, therapeutic use of, 100,

110, 111, 124-130
use in opithelioma, 161 (see names

of diseases and organs)
Pleochroie halos (sec Mica)
Polonium, discovery of, 18 (see Radium

"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 treatment, 159, 160,

212
Proctitis, following radium treatment,

225
Prostate gland, carcinoma of, treatment,

209-211

Protactinium, 20
Protective devices, against radiations,

147, 323, ?,24

Pruritus, treatment of, 294
Psoriasis, treatment of, 286, 288

Radiation, teehnic 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
iluorescence caused by, 71
light emitted by, 71
penetrability of, 69 70, 150-152
phosphorescence, caused by, 71
photographic action of, 71
properties of, 40
secondary, formed by screens, 48

produced by rays, 44
surface, 116, 117
Radioactive deposit, active change, 26

administration of, 311

collection, on foil, 114
on wire, 115

described, 26, 114

pathologic effects of, 311

INDEX

389

Radioactive deposit — Cont'd
rate of decay, 115
slow change, 26
solution of, 38, 39, 115
therapeutic use of, 26, 27, 114, :;in

313

Radioactive rays (see Radiation and Ra-
dium Rays)

Radioactive substances, defined, 40
period of decay, 18
series described, 19
transformation theory, 18, 27
Radioactivity, discovery of, 17
Radiographs, x-ray and made with ra-
dium radiations, 71
Radiosensibility (see Sensitiveness to ir

radiations)

Radiothorium, discovery of, 18
Radium, administration of, 310, 311
analgesic action of, 295
atomic weight, 22
chemical nature of, 22
content of various organs of body, 312
decay, 24,

period of, 18

disintegration, theory of, 27
effects of on tissues, morphologic, 31G

physiologic, 313-315
elimination from body, 311-313
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
Radium B, described, 26

properties, 28
Radium C, described, 26

properties, 28
Radium C,, described, 26
Radium C2, described, 26

properties, 28
Radium D, described, 26

properties, 28
Radium E, described, 26

properties, 28

Radium F, or polonium, 18, 26
effect on skin, 88
properties, 28

Radium G, atomic weight, 26, 27, 28
described, 26
properties, 28
Radium emanation, absorption of, by

different substances, 24, 25
administration of, 311
activity of measurement, 35-38
atomic weight, 24
baths, 311

chemical behavior, 24
decay, 25

period of, 25, 34

Radium emanation — Cont'd

rate of, 33, 111
inhalation of, 311
preparation of, 29-39, 111, 112
solution of, preparation, 38, 39

therapeutic use, 81
spectrum, 24
Radium rays, effect of, biologic, 88-102,

149-150

ionizing, 42, 69, 89, 118
on animal life, lower forms, 74, 75

higher 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 marrow, 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 heart, 313, 314, 320
on kidneys, 84
on leucocytes, 81, 304, 316
on liver, 84

on lymphatic 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 80, 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 intratumoral radiations, 107,

108
due to surface radiations, 103-106,

295, 296
following treatment of epithelioma,

189

of fibroids, 242, 243
of spleen, 307
inflammatory, 75, 88, 103-105, 149,

245, 322

leukopenia brought on, 323
menopause, 241-243
nausea, 103

physiologic, 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

Rhinology, use of radium in, 298
Rhinoscleroma, treatment of, 286
Ringworm, treatment of, 295

Sagnac, Rays of, 48

Salivary glands, effects of radium rays on,

84
Sarcoma, treatment with radium rays, 97,

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 application,

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 angiomata, 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, 207
of superior maxilla, 199
of thyroid gland, 203
of urethra, 208, 209
esophagus, 151, 205, 206
fibromyoma of uterus, 242, 243
keloids, 247-249
lupus erythematosus, 289, 294
lupus vulgaris, 285
metritis, 244

nevus, pigmented, 282, 283
sarcoma, 232, 233
skin, 77-79, 143

tuberculosis verrucosa cutis, 284, 285
tumors, 91, 117

parotid, 204

various types, 46, 47, 150, 151
"window" 47
(see also names of diseases and organs

treated)
Sebaceous glands, use of radium for, 295

Selective absorption, defined, 104
Selective action, of radium rays, 104
Selective reaction, 104, 245
Sensitiveness to irradiations, carcinomata,

158-160
x rays, 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 rays on, 76-80, 87, 127-

128, 155, 245
histologic changes of, due to radium

rays, 76-80, 127, 128, 245
treatment of, radium, 245-296
chronic infections, 284-286
disorders of appendages of, 295, 296
hypertrophies, 294
inflammatory 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 rays 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 by thorium

X, 317
Sweat glands, use of radium in treatment

of, 295

Sycosis vulgaris, treatment of, 295, 296
Synovial lesion of skin, treatment of, 294
Syphilis, skin eruptions,' treatment of, 286

Technic of radiation, 146-157 (see also
names of diseases amenable to
radiation)

Telangieetasia, following radium treat-
ment, 105, 106, 269, 273, 295
Temperature due to radium reaction, 10."?
Testis, carcinoma of, treatment, 228

effect of radium rays on, 84
Thermolumiuescence, 71
Thorium, discovery of radioactive proper-
ties of, 18
emanation, 20

Thorium 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— Cont 'd

on spleen and other organs, 80
effects of large injections of, 316, 318
in treatment of anemia, 320

leukemia, 307

Thyroid gland, enlarged, treatment of, 309
Thyroid and tliymus glands, carcinoma

treatment, 203

effect of radium rays on, 83
"Tinnitus aurium, " treatment of, 298
Tissue, connective, effect of radium rays

on, 81, 82
Tissues, effect of radium rays on, 77-80

malignant, treatment, 79, 80
Tobacco, as affecting leukoplakia, 189
Toiles, described, 110

use in treatment of nevus, 273
Tongue, carcinoma of, treatment, 198
Tonsil, carcinoma of, treatment, 198, 19!)
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
"ba.re, " 112, 113 (see also ampoules)
for radium salts, 109, 110
Tumors, effect of radium rays on, 89, 90-

92, 144, 145
intratumoral radiations, 107, 144, 145,

155-157

screens in treatment for, 91, 117, 204
treatment of, 153-157, 158-160
Jirnin, 233

malignant, inoperable, 159, 160
malignant, operable, 159
mediastinal, 230, 231
of eyelids, 234, 235

Tumors, treatment of — Cont'd.
parotid, 203, 204
subcutaneous and submucous, 274-280

Uraninite, 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, carcinoma of, treatment, 94, 150,
loi, 221-227

Vagina, radium treatment of, 147
Vernal conjunctivitis, treatment with ra-
dioactive deposit, 114, 297
Vocal cord, sarcoma of, treatment, 302
Vulva, carcinoma of, treatment, 208

Waters, mineral, radium emanation in, 25
Warts, treatment of, 294

X-rays absorption of, 49, 50
discovery of, 17

effect on blood making organs, 86
immunity experiments with, 99, 101
keratosis, treatment of, 294
penetrating power of, 44
radium treatment following use of, 188
reaction causing menopause, 242
scars treated with radium, 188
sensitiveness of carcinomata to, 159

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