U T PW .
.' I .
PCC. NO.
METABOLIC CHANGES IN HUMANS
FOLLOWING TOTAL BODY IRRADIATION
RCC1.950321.012
DASA-1633
REPORT PERIOD
May 1, 1963 to February 29, 1964
Eugene L. Saenger. M.D. Ben I. Friedman, M.D. James G. Kereiakes, Ph.D. Harold Perry , M.D.
Defense Atomic Support Agency
Washingon, D.C. 20301
Preparhg Agency
University of Cincinnati College of Medicine
Cincinnati General Hospital Cincinnati, Ohio 45229
DA-49446-XZ-029
c I
io32 006 2 2 6 1.01 2
DASA-1633
j
FOLLOWING TOTAL BODY LRRADIATION~
REPORT PERIOD
May 1, 1963 to February 29, 1964
Eugene L. Saenger, M.D. Ben I. Friedman, M.D. James G. Kereiakes, Ph.D. Harold Perry, M.D.
Defense Atomic Support Agency
Washington, D. C. 20301
Preparing Agency
University of Cincinnati College of Medicine
era1 Hospital nio 45229
/ 1
r
b
?
DOC Availability Notice
Qumliiied requcmtera ray obtain copiem O f thia report from DDC.
.
ABSTRACT
These studies a r e designed to obtain'information which is necessary to
estimate combat effectiveness of troop6 and to develop methods of diagnosis,
prognosis, prophylaxis and treatment of radiation injury. At the present time
parameters of active investigation a r e clinical findings, hematologic effects,
profile scores ,' miscellaneous laboratory tes t s , deoxycytidine excretion in
the u r i n e , xanthurenic acid excretion in the urine, chromosome changes in
leucocytes, immunologic studies and the use of autologous bone marrow.
Six patients were given from 149r to 231r (100-150 rad) total body i r rad-
iation from a Gobo source.
vomiting with n a u ~ e a lasting 48 hours.
found 25 to 35 days af ter irradiation.
O d y one of the patients had prodromal nausea and
The lowest hematologic values were
Deoxycytidine was found i n increased amounts in the urine from patients
after total body irradiation. In rats much la rger amounts were found in the
urine af ter 5OOr and 800r whole body irradiation than af ter l e s s e r doses.
Studies by Dr. Anthony Luzzio, U.S. Army Research Laboratory, Ft. Knox,
Kentucky, indicate there may be an immunologic post irradiation alteration in
human gamma globulin antigenicity.
Combat effectiveness would be relatively maintained with an exposure up
to 200 rad, though a second exposure would resul t in significant troop ineffec-
tiveness.
Animal experiments described herein were conducted according to the principles of laboratory animal c a r e as promulgated by the National Society fo r Medical Research.
1. Introduction 2. 3. Selection of Subjects 4. Technique of Study 5. Analysis of Data 6. Dosimetry 7. Clinical observations 8. Hematology and Profile Scoring 9. Deoxycytidine 10. Quantitative Precipitin Test U. Chromosome Studies 12. statistics I
13.
Aims and Scope of the Project
Proposals for Human Study Program
Publications
Summary
Tables - I II Total Body Radiation Dosimetry ILI IV Deoxycytidine Excretion in Humans V
VI Incidence of Endoreduplication
P re and Post Irradiation Observations
Partition of Profile Scores Based on "Net Erythrocyte" Score
Urinary Excretion of Deoxycytidine in Total Body X-Irradiated Rats
Appendix A
Clinical Summaries - Cases # 0 3 0 - #037
Page 1
1-2 2
2-3 3 3
3-4 4-5 5-6
b b 7 7-9
9
10
11 12 13 14 15
16-18
19-28
Figures
Fig. 1 - Quantitative Precipitin Test 29 Fig . 2 - 30 Printout of Total White Count - No Previous Therapy. Low Dose
I. INTRODUCTION
This project was initiated in February 1960 and this report presents
data accumulated from May 1, 1963 through February 29, 1964. The previous
reports of November 1961 and April 1963 (DASA 1422) cover the data compiled
pr ior to May 1963.
Six additional patients have received from 149 r to 231 r (100-150 rad)
total body irradiation in the period covered by this report.
2. AIMS AND SCOPE O F THE PROJECT
These studies a r e designed to obtain new information about the metabolic
effects of total body and partial body irradiation so as to obtain a better under-
standing of these acute and subacute effects i n human beings. This information
is necessary to provide knowledge of combat effectiveness of troops and to de-
velop additional methods of diagnosis, prognosis, prophylaxis and treatment of
these injuries.
At the present t ime parameters of active investigation are:
1. Clinical findings
2. Hemograms and profile scores
3. Miscellaneous laboratory tes ts (serum urea nitrogen(SUN), blood
cultures, C-Reactive Protein and bone marrow aspiration)
4.
5. Xanthurenic acid i n urine
6.
7.
Deoxycytidine and other nucleasides in urine
Chromosome changes in white cel ls
Quantitative precipitin tes t (Dr. Luzzio, U. S. Army Medical
Research Laboratory, Ft. Knox, Kentucky)
- 2 -
0 . Levels of s e rum lipoproteins (Lt. Col. E. C.
Knoblock. Walter Reed Army Institute of Research)
9. Use of autologous marrow
3. SELECTION O F SUBJECTS
Only patients with metastatic o r incurable neoplasms a r e eligible for
such studies.
a r e sought.
stable hemogram a r e required.
disease on the observed metabolic changes remains a problem.
Patients who have solid tumors which might be radioresistant
Relatively good nutritional status. normal renal function and a
Interpretation of the effect of the underlying
Patients who have had no previous radiation o r chemotherapy a r e
generally used though some patients SO previously treated have been studied.
It is possible to isolate the effect of previous radiation by such studies.
4. TECHNIQUE OF STUDY
The design of the study is such that the patient se rves as his own
A pre-irradiation control period of one to two weeks is utilized. control.
ever , with the increased levels of radiation, the post-irradiation period has been
extended to six or eight weeks.
How-
Five observations a r e made in the pre-irradiation period. Observations
currently made a r e l isted in Table I.
tained at standard tes t t imes as described by Thoma and Wald (See section on
Analysis of Data).
Pos t irradiation specimens are then ob-
Patients have been studied on the Tumor Ward and the Metabolic Ward
of the General Hospital.
t h i s study.
One bed on the Metabolic Ward has been allotted for
- 3 -
During the pre-irradiation period, the patient's records a r e reviewed
by t h e physicians to be certain that the contribution of the underlying disease
can be evaluated. One or two sham irradiations a r e given to permit accurate
dosimetry and obtain cooperation by the patient.
possible subjettive reactions resulting from the treatment. Other physicians,
nurses, technittans and w a r d personnel a r e instructed not to discuss post-
irradiation symptoms or reactions with the patient.
There i s no discussion of
5. ANALYSIS OF DATA
Collection of data continues essentially according to the plan of Thoma
and Wald (J. Occup. Med. 1:420-447, 1959) and described in section 3 of Medical
Aspects of Radiation Accidents, E.L. Saenger, ed., U.S. Government Printing
Office, 1963. (Table I).
All data a r e recorded on score sheets and then t ransferred to IBM
Thus all information together with the appropriate machine programs cards.
i s available for analysis by other centers o r interested individuals.
Profile scoring is used to estimate the effect of previous irradiation
or chemotherapy.
6. DOSIMETRY
The method is described in Appendix B of DASA 1422.
The methods of dosimetry remains the same as in the report of April
1963.
7. CLINICAL OBSERVATIONS
The dosimetry for the patients is given in Table II.
Six additional patients have been studied since the las t report. They
received from 149 to 231r of total body radiation (total midline dose in a i r
without a phantom).
A.
Clinical summaries a r e attached to this report a s Appendix
Patient #032 received only sham because of a low white count and hypoplastic
- 4 -
marrow when checked in the pre-radiation period.
due to progression of her disease.
Patient #034 was abandoned
One (#031) of the patients irradiated had radiation to her uterus tbirty-
four years prior to total body irradiation.
piperazine derivative (A8103 - Abbott) eight months before total body radiation.
The four other patients.were untreated.
One patient (#030) had received a
Only one of the patients had prodromal symptoms of nausea and vomit-
ing with persistence of nausea to 48 hours after a dose of 227 r (150 rad).
had received no previous therapy.
She
As has been seen before, there appeared to be increased lassitude.
Quantitation of this observation will require specific procedures for performance
testing.
8. HEMATOLOGY AND PROFILE SCORING
The presence of a "plateau" o r "peak" in the white blood cell count h a s
continued to be observed.
until about the twentieth day.
between the twenty-fifth and thirty-€ifth day after radiation.
It is noted at approximately ten days and continues
The lowest hematologic values a r e observed
Mild lymphocytopenia was seen on the treatment day. Occasional giant
polymorphonuclear granulocytes were seen in two patients.
Profile scoring was continued in the same manner a s described in
the Summary Report of April, 1963. Appendix B.
radiation score and total continued to be of value in ascribing the importance of
radiation i n precipitating demise. "Net erythrocyte" score was again used. In
this group of patients "net erythrocyte" score did not introduce significant change
from a score based on the hematocrit.
Delineation of disease score,
Table III summarized the data based on
profile scoring.
9. DEOXYCYTIDINE
Four additional patients have been evaluated in regard to urinary
excretion of deoxycytidine (dCT). This substance was found in increased
yields i n the post radiation phase for periods up to 48 hours, (See Table IV).
It i s apparent from the first six patients that we have not a s yet demonstrated
a dose effect relationship.
difficulties with the technical procedure although it may be due to effect of
concomitant disease. Because of the wide confidence l imits noted in several
of our concurrent r a t experiments we suspect that the problem i s a technical
The lack of such a relationship probably represents
one.
Four patients who have not received radiation but who had other ill-
nesses have been studied for urinary dCT excretion.
thermal burn, f racture , infection and cancer. None showed dCT.
human so fa r studied who h a s shown urinary dCT i s patient #030 who had re-
ceived chemotherapy with A 8103 (Abbott) about 8 months pr ior to irradiation.
The observation that dCT is not excreted in a t least a few other disease states
indicates that i t s excretion may a t least be relatively specific for radiation.
These conditions included
The only
Some experiments have been car r ied out using the Wistar rat. Groups
of 12 male ra ts were exposed a t doses of 0, 200, 500 and 800 rad. Rats excrete
some dCT normally and pre-radiation levels ranged 0 f 100
(Table V).
The ra t s exposed at 500 rad showed an increase over those receiving 200 rad.
There was no significant difference between dCT levels at 500 and 800 rad.
pg/24 hours,
All ra ts showed an increase in deoxycytidine excretion post radiation.
Laboratory techniques for dCT analysis in urine have been quite tedious
and have not as yet reached the desired degree of accuracy. The entire pro-
cedure is being re-evaluated to develop a method by which la rger numbers of
specimens can be assayed in shorter times.
10. QUANTITATIVE RRECIPITIN TEST
Serum from our patients h a s been stored and sent to Dr. Anthony J.
Luzzio of the U.S. Army Medical Research Laboratory, Ft. Knox, Kentucky.
The serum has been examined for radiation altered human serum gamma
globulin. [Luzzio, A. J. The Serologic Specificity of Radiation Altered Human
Serum Gamma Globulin, The Journal of Immunology, 90:224. Feb., 1963).
Serum from several patients showed a bimodal post irradiation increase in this
materialJFig. 1).
serum gamma globulin as a result of in vivo irradiation.
These data suggest an alteration i n antigenicity of human
U. CHROMOSOME STUDIES
Observation of peripheral blood chromosome cultures h a s continued.
A finding of particular interest has been the observation of endoreduplication.
This phenomenon has been observed in eleven patients with cancer and in one
control. It has been seen before and after irradiation. Four patients have been
studied in detail (Table VI).
occurrence seems t o be a radiation effect.
th i s observation is associated with irradiation or the presence of malignancy.
Additional studies a r e being car r ied on i n controls and patients with malignancy
to evaluate further the role of irradiation.
In at least one patient increased incidence of this
At t h i s time it is not clear whether
- 7 -
12. STATISTICS
Computer analysis of the hematologic data on the first twenty-nine
patients has started. The patients have been divided into four groups:
1) Those receiving 100 rad o r lees total body irradiation who
have not had previous irradiation; 2) those receiving 100
rad o r l e s s total body irradiation who have had previous
irradiation; 3) those receiving more than 100 rad of
total body irradiation who have not had previous irradiation;
and 4) those receiving more than 100 rad of total body
irradiation who have had previous irradiation.
Printouts of each group and of the combined groups for each parameter
were constructed with the abscissa in days post irradiation. On the ordinate
the means of the pre-irradiation values were standardized a t unity (1). There-
fore all post irradiation values were related to the mean of the pre-irradiation
observations (Fig. 2 is a representative printout).
A fall in hemoglobin, hematocrit and reticulocytes in patients who re-
ceived more than 100 rad total body irradiation was observed.
seemed to influence the immediate lymphocyte fall and la te r decrease in mono-
cytes of the high dose patients.
creased in all groups but to a greater extent in patients given more than 100 rad
who had received previous irradiation.
Previous therapy
Total white cells in the peripheral blood de-
13. PROPOSALS FOR HUMAN STUDY PROGRAM
We propose t o continue observing d i n i c d and hematologic effects of
irradiation with a Go-60 unit a t a rate of approximately 5.4 r lmin a t 282 cm.
Exposures wil l be total and partial body, bilateral and unilateral. Storage and
- 0 -
reinfusion of autologous bone marrow will be accomplished i n the facility which
h a s been established.
The determination of urinary excretion of deoxycytidine, chromosome
changes and immunologic alterations will continue.
vestigations of performance testing will be made.
Further exploratory in-
Preliminary discussions regarding studies in volunteers will be insti-
These wil l , of necessity, require considerable perspicacity and con-
However, it is our hope such a program will be feasible.
tuted.
templation.
a) Clinical and hematological observations of cobalt 60 irradiation
Exposures will be given at dose rates of 5.4 r /min a t 282 cm. w i l l continue.
to the whole body, partial body (upper and lower portions and unilateral).
Facilities for storage and reinfusion of bone marrow a r e j u s t
being installed.
which marrow storage w i l l be carr ied out on subjects.
storage and reinfusion is to protect subjects who receive doses in excess of
150 rad in the event of bone marrow failure.
200 - 300 rad.
Trials on cadavers will be made for the next four months after
The purpose of marrow
We hope to utilize doses between
b) Deoxycytidine studies - The assay of urinary deoxycytidine w i l l
be re-evaluated so as to simplify the techniques a5 discussed above.
The most interesting aspect of dCT is the mechanism of urinary
excretion.
studies with C-14 labeled and tritiated materials a r e planned.
1) Clearance from blood
2) Determination of the existence of a renal threshold
3) Meaaurement of a respiratory component of C-14
labeled dCT (i.e. C 0 2 ) .
In order to attempt to clarify this problem further the following
14
These experiments w i l l not, of course, answer the question posed
previously as to whether dCT i s produced because of interference with
synthesis o r because of increased breakdown oi nuclear DAW. Bur antil tne
metabolism of dCT is better understood in me human being, the elucidation
of t h i s problem by the administration of labeled precursors of dCT cannot
be undertaken.
Initially the method of breath analysis for C 14 0 2 using the Carey
vibrating reed electrometer will be undertaken with C14 labeled glucose and
glycine in order to develop the methodology at a lower COS(.
The initial labeled dCT wi l l be labeled in the 2 position of the pyrimidine
ring. Subsequently uniformly labeled tritiated mater ia l will be used. These
studies will be car r ied out i n patients other than those receiving whole body
irradiation.
of DNA precursors for the labeling of dCT in irradiated humans.
La ter studies in succeeding years envision the administration
c) Immunological studies continue with plasma samples being sent
to Dr. Luzzio at the U.S. Army Medical Research Laboratory, Ft. Knox,
Kentucky.
PUBLICATIONS
Deoxycytidine in Urine of Humans after Whole-Body Irradiation, Helen K.
Berry , Eugene L. Saenger, Harold P e r r y , Ben I. Friedman, James C.
Kereiakes and Carolyn Scheel.; Science, Val. 142, No. 3590, pages
396-398, October 18, 1963.
- 10 -
SUMMARY
1. Six additional humans with cancer have received 149-231 r (100-150 rad)
total body irradiation.
2. Deoxycytidine has been found in increaaed amounts in the urine from
patients following whole body irradiation. Much larger quantities of deoxycy-
tidine have been found in the urine of rats af ter 500 r and 800 r whole body
irradiation than after l e s se r doses.
3. The observation of endoreduplication in the peripheral blood chromo-
some preparatians may be related to malignancy but w a s increased following
total body irradiation.
4. Studies by Dr. Anthony Luezio, U.S. Army Research Laboratory,
Ft. Knox, Kentucky, indicate there may be an immunologically distinct bimodal
post irradiation alteration in human gamma globulin antigenicity.
5. Computer analysis of data f rom the f i r s t 29 patients irradiated suggests
a fall i n the hemoglobin, hematocrit and reticulocytes in patients receiving more
than 100 rad total body irradiation. The immediate fall i n lyrnphocyfes and la ter
fall of monocytes in patients receiving more than 100 rad seemed associated
with previous therapy.
striking degree in patients who had previous therapy and were given a high dose.
Total white cells decreased in all groups but to a more
6. Combat effectiveness would be maintained relatively well with an
exposure up to 200 rad.
significant troop ineffectiveness.
However a second exposure would probably result in
- u -
TABLE I
PRE AND POST IREVLDIATION OBSERVATIONS
1.
2. T e m p e r a t u r e , pulse , and resp i ra t ion
3. Body weight
4. Medications - f luids , ant ibiot ics , s t e ro ids , na rco t i c s
5.
Complete h is tory and physical examination
Hematology - Hgb., RBC, WBC. differential , hematocri t , p la te le t s ,
re t iculocytes , erythrocyte sedimentat ion r a t e
6. Urine
a) volume
b) routine ur ina lys i s
c ) chromatography fo r deoxycytidine
d) chromatography for xanthurenic ac id
7. Serum urea nitrogen
8. Lipoproteins
9. Quantitative precipi t in t e s t
10. Chromosome studies
U. Blood cul tures
12. C reac t ive protein
13. Bone m a r r o w asp i ra t ion
TABLE II
TOTAL, BODY RADIATION DOSIMETRY
Patient No.
030
0 31
033
035
036
037
Midline Air Dose Roentgens
149
155
152
227
15 3
2 31
Mi&c Tissue Dose
Rads
10 0
100
10 0
150
10 0
150
030
0 31
033
035
036
037
TABLE XU
PARTITION OF PROFILE SCORES BASED ON
“NET ERYTHROCYTE” SCORE -
Case No. D i s e a s e S c o r e
T e s t C u m h t i v e
0.8 16.0
2.0 41.2
1.4 25.2
0.0 00.0
1.4 24.1
1.0 10.0
Radiation S c o r e
T e s t Cumulative
0 .5 34.0
0.0 1.1
1.3 27.1
1.0 95.7
4. 6 100.2
ll. 7 33.7
Totd Score
T e s t Cumulative
1.3 50.0 (89)
0.0 42.3 (89)
2.7 52.3 [ b l )
1.0 95.7 (61)
6.0 125.3 (47)
12.7 47.7 ( 2 6 )
( ) = Days p o s t radiation
,032 and 034 did not r e c e i v e radiation
Pt.
027
029
030'
031
0 3 3
-
- 14 -
TABLE IV
DEOXYCYTDINE EXCRETION IN HUMANS
Age Sex k Race
17 M W .
-
63 F w , 54 M NW
81 F NW
64 M NW
Diagnosis Dose (rad) Total dCT (mg)
Ewing's Sarcoma 150 182
Ca. Breast 150 52
Ca. Stomach 100 66
Ca. Breast 100 25
Ca. Colon 100 30
t Rec'd A-8103 pre rad. Had 8 mg. dCT pre rad.
TABLE V
URINARY EXCRETION OF DEOXYCYTIDINE IN TOTAL BODY
X-LRRADIATED RATS
-
Deoxycyticiine Levels (t~'g/rat)
Urine Collection Period O r 200 r 500 r 800 r -
Pre - 24 hours 42( 0-90 ) * 20 ( 0-60 ) 18 ( 0-70 ) 30 ( 0-100)
Post 0-24 hours 62 (36-120) 484 (248-585) 1755 (630-3050) 16U (1050-2600)
24-48 hours 39 ( 0-100) 97 ( 50-130) U 8 ( 15-225 ) 236 ( 66-450)
48-72 hours 19 ( 0-48) 62 ( 10-YO) 70 ( 0- 130) 114 ( 10-280)
* numbers in parenthesis indicate range of values.
- 16 -
TABLE VI
INCIDENCE OF ENDOREDUPLICATION (Patients)
Chromosome Cells Showing Sampling Date Endoredupbcation
s.n. - lll15 I 6 3 0
U118163 0
U122163 0
U/24/63 100 Rad Total-Body Irradiation
11124163 2 hr post irradiation 0
Ill24163 b hrpost irradiation 0
Ul25163 8
ll1291Q3 0
12/6/63 0
12/13 I 6 3 0
1 2 / 2 0 1 6 3 0
12 I24 I 6 3 1
M.R. - l O l l 8 1 6 3 0
10 123 I63 1
10l25163 0
10/27/63 150 Rad Total Body Irradiation
10/27/63 2 hr post irradiation 2
10/27/63 6 hr post irradiation 1
10 I281 63 1
No. of Mitosing Cells Counted Incidence qo
2272 0.00
18’14 0.00
3208 0.00
2029
3920
1401
2180
la9
1522
2068
2015
1942
2500
1604
1862
563
1425
0.00
0.00
0.57
0.00
0.00
0.00
0.00
0.05
0.00
0.04
0.00
0. Ll
0.18
0.07
- 17- Page 2 of Task VI
TABLE VI (contmued)
Chromosome Cells Showing Sampling Date Endoreduplication
M.R. (continued) - U11163 0
l l J 8 1 6 3
l.l/15/63
0
0
Ul22 I63 0
U126163 0
3/8/63 17
3/11/63 0
31141 63 pre-irradiation 4
3/14/b3 150 Rad Total Body Irradiation
3/14/63 post-irradiation 74
3/15/63 1
3/20/63
3/26/63
0
0
4/1163 3
4/8/63 1
4/15/63
M.L. - 6/4/63
6/U/63 2
6/14/63 3
No. of Mitosing Cells Counted
1383
3873
1372
3073
3633
12743
1966
1993
7 9 7 9
59
4 0
55 6
1281
2810
5 5
18196
1254
2784
0. 00
0.00
0.00
0.00
0.00
0.13
0.00
0.20
0.93
1.69
0.00
0.00
0.23
0.04
0.00
0.04
0.16
0. u
- 18 - P a G e 3 of Table V I
TABLE V I (continued)
Chromosome Cells Showing No. of Mitosing Sampling Date Endo reduplication Cells Counted Incidence %
M.L. (continued)
6/16/63 100 Rad Total Body Irradiation
6/16/63 2 hr. post-irradiation 1
6/16/63 6 hr. post-irradiation 6
6/17/63 11
6/21/63
6/28 I63
7
0
7/5/63 3
7/U/63
7/16/63
2
21
83
2928
3209
5115
1558
3260
2256
11774
1.20
0.20
0.34
0. 14
0.00
0.09
0.09
0.18
- I7 -
APPENDIX A
CLINICAL SUMMARIES
- 20 -
Study No. 030
Patient J.D.
Chart No. 382572
This patient w a s a 54 year old Negro male who had a laparotnmy performed
on September 11, 1962.
was inoperable due to widespread metastases to the ceIiac and middle pelvic nodes,
the peritoneum and omentum. A gastrojejunostomy was performed. (CGH SP
62-2445). Following surgery. he had increased appetite and cessation of vomit-
ing, but severe pain in the abdomen continued. He was discharged on September
27. 1962.
The operation revealed a carcinoma of the 8tomach which
On October 9, 1462. he was placed on A-8103, 40 mgm/day, a s well a s
The chemotherapy was dis- medication for control of pain and gastric spasm.
continued in December, 1962.
On May 17, 1963, the patient was admitted to CGH with complaints of nausea
and vomiting of three weeks duration. A 10 cm. m a s s was present in the epigas-
trium.
The patient received 100 rad total body radiation on June 6 , 1963.
The midline air dose was 149 r.
(Total
absorbed dose a t axis).
following treatment.
related to his radiation therapy, but was associated with a partial obstruction a t
the operative stoma.
thrombocytopenia with the leukocyte and platelet counts returning to pre-treatment
levels by sixty days post radiation. A mild anemia developed approximately one
He had no symptoms
The patient had some nausea and vomiting which was not
Thirty days after treatment he developed leukopenia and
- 21 -
Study No. 030 (continued)
week after treatment and persisted through seventy-five days post radiation.
He subsequently received chemotherapy, but expired December 23,
1963. No autopsy was obtained.
Study No. 031
Patient M.L.
Chart No. ll6l58
The patient is an 81 year old Negro female who had the diagnosis of
carcinoma of the right breast made in February, 1958. On March 7, 1958, a
right radical mastectdmy w a s performed. (CGH SP 58-391).
On May 14, 1963, the patient was admitted to CGH with a m a s s in the
left breast which had been slowly increasing in size for one year.
also a mass over the hepar. Biopsy of the breast on May 23, 1963, revealed
carcinoma of the breast (CGH SP 63-1301) and on May 28, 1963, a simple
mastectomy was performed. (CGH S P 63-1379).
There was
The patient had radiation therapy for fibroids thirty four years prior to
the first breast amputation. She did not receive post-operative radiation therapy.
On June 16, 1963, the patient received 100 rad total body radiation. (Total
absorbed dose a t axis). The midline air dose was 155 r. She bad no symptoms
following treatment. Thirty days after treatment leukopenia and thrombocyto-
penia developed.
days and the leukocytes by seventy-five days post radiation.
the patient had a mild anemia with the hernoglobin averaging 10.5 grams, the
hematocrit 35%. Since treatment there has been improvement in the anemia,
and seventy-five days post radiation her hemoglobin was ll.9 grams, hematocrit
38%.
The platelet count returned to pre-treatment levels by sixty
Pr ior to treatment
The patient is being followed and has received local Cobalt 60 therapy.
Study No. 033
Patient A.J.
Chart No. 363128
The patient was a 61 year old Negro male who had the diagnosis of adeno-
carcinoma of the colon made in March, 1959.
colostomy was performed March 24. 1959. (CGH SP 59-980).
A colectomy and ileotransverse
On May,28, 1963, the patient was seen in Medical Clinic with complaint
of weight loss and upper abdominal pain of several months duration. At this time
the presence of a large r igh t upper quadrant mass was noted and he was referred
to Tumor Clinic.
The patient wac admitted to CGH on June 24. 1963, for evaluation for total
body radiation with a diagnosis of I) recurrent carcinoma of the colon with rnetas-
tas is to the l iver , and 2) abdominal hernia.
therapy.
He had received no previous radiation
On July 7, 1963, he received 100 rad total body radiation. (Total absorbed
He experienced no symptoms f rom dose at axis).
radiation.
mittent pain in the hepatic region. He had some slight relief from pain, and a
slight decrease in size of the hepatic mass. Twenty-six days after treatment,
the patient developed leukopenia and thrombocytopenia with the leukocyte and
platelet counts returning to pre-treatment levels by thirty-nine days post radiation.
The midline air dose was 152 r.
Pr ior to treatment, the patient's major complaint w a s severe inter-
On August 6 , 1963, the patient was discharged, but on August 20 he was
readmitted with complaint of severe anorexia. nausea, weakness, and abdominal
pain. His course
continued downhill and the patient expired October 1, 1963.
His WBC rose to 17,000 and chest x-ray revealed pneumonia.
No autopsy was obtained.
- 24 -
Study No. 035
Patient M.R.
Chart No. 415556
The patient is a 53 year old Negro female who had the diagnosis of car-
cinoma of the right breast with metastases to the skin and right and left supra-
clavicular nodes made in April, 1963. She a l so had a la rge (CGH SP 63-952).
abdominal mass and on May 1. 1963, a n abdominal hysterectomy for l a rge uterine
fibroids was performed. (CGH SP 63400) .
On October 15, 1963, the patient was readmitted to CGH for evaluation
for total body radiation. She had no previous radiation therapy o r chemotherapy.
On October 27, 1963, the patient received total body radiation of 227 r
(midline dose in a i r ] , which was.equivalent to 150 r ad (total absorbed dose at axis).
Approximately two hours after treatment she complained of anorexia. nausea and
vomiting, and "feeling lightheaded". The vomiting abated af te r approximately
six hours, hut anorexia and post prandial nausea persisted for forty-eight hours.
The patient has also complained of weakness and fatigue since treatment but ad-
mitted, upon questioning, that s h e also experienced these symptoms p r i o r t o
treatment.
Hemoglobin 12.4, hematocrit 41%. RBC 5,100,000, WBC 8,400, platelet 250,000.
Seventeen days post treatment the blood values had fallen tO: Hemoglobin U.2,
hematocrit 36%, RBC 4,200,000, WBC 3,800, platelet 166,000.
Hematological studies before treatment revealed average values of:
On November 2 0 , 1963, 24 days post treatment, the patient's platelet
count was 50,400. It continued to drop to a l o w of 36,560 thirty-six days post
treatment. Between 28 and 47 days post treatment. guaiac positive stools and
micro-hematuria were observed. By 54 days post treatment the platelet count
- 25 - Study No. 035 (continued)
had returned to pre-treatment levels and upon examination 61 day5 post treat-
ment the stool was guaiac negative.
3 The WBC reached i t s lowest point, 1100 cells/mm , 33 days pos t treat-
ment. It remained between 1100 and 2500 until 47 days post when it rose to
3,150. It continued to climb and 75 days post treatment the WBC was 7 ,450 .
Bone metastases were noted in February, 1964.
- 26 -
Study No. 036
Patient S.H.
Chart No. 301648
The patient is a 64 year old Negro male who was first admitted to CGH
on November 12, 1954.
and the diagnosis of colloid adenocarcinoma of the colon was made.
54-2560). The patient was readmitted
to CCH on October 7, 1963 and on November 1, 1963 an exploratory laparotomy
was performed which revealed sigmoid carcinoma, unresectable. A loop
colostomy was performed and in addition a biopsy was obtained which revealed
colloid carcinoma (CGH SP 63-2704).
A r ight colectomy was performed November 23, 1954
(CGH S P
None of 20 lymph nodes were involved.
The patient had received no previous radiation therapy. On November
24, 1963, 100 rad total body radiation was administered &otal absorbed dose
at axis). The air dose a t the body mid axis was 153 r.
The patient tolerated the procedure well and experienced no symptoms
following radiation.
values were:
reticulocytes 0. 8%, sedimentation rate 50.
Prior to treatment. the patient's average hematology
hemoglobin 10.8, hematocrit 3776, WBC 6,400, platelets 250,000,
The patient's blood count reached a low at 26 days post radiation of:
hemoglobin 9.5, hematocrit 30%, WBC 2,000, RBC 3.7. reticdocytes 0.5%,
platelets 64,000. with an increase in uncorrected sedimentation rate to 57.
At 44 days post treatment the count appears to be rising, but has not yet returned
to pre-treatment levels. Progression of the underlying disease continues.
Study No. 037
Patient W.R.
Chart No. 42406l
The patient was a 64 year old Negro male who was first admitted to CGH
Gastrointestinal s e r i e s on November 19, 1963, revealed on November 19, 1963.
cardiospasm of the distal third of the esophagus, possihle lesion of the cardio-
esophageal junction, and grossIy abnormal stomach wall. with changes con-
sistent wi th carcinoma of the stomach.
carcinoma was confirmed by esophagoscopy November 22. 1963, and left scalene
lymph node biopsy November 23, 1963. (CGH SP 63-2917). Due to the distant
disease, 1) left scalene lymph node, 2) a definite evidence of Blumer's shelf,
the patient was immediately worked up fo r total body radiation.
no previous radiation therapy.
The diagnosis of metastatic signet ring
The patient had
On December 15, 1963, the patient received 150 r ad total body radiation
(total absorbed dose at axis), i. e., 231 r in air. He experienced no symptoms
following radiation. P r i o r to treatment, the patient's average hematology values
were: hemoglobin 12.3, hematocrit 37%, RBC 3.7 million, WBC 7,800, reticu-
locytes 0.7%, platelets Z25,000, sedimentation ra te 40 mm.
radiation, the values had fallen to: hemoglobin l l .4, hematocrit 34%, RBC 3.42.
WBC 1,500, reticulocytes 0.5%, platelets 54,000 and the uncorrected sedimen-
tation r a t e increased to 56 inm.
By 23 days post
On December 26, 1963, U days post radiation, the patient refused re -
admission to CGH, but agreed to continue the follow-up on an out-patient basis.
- 28 -
Study No. 037 (continued)
However, on January 10, 1964. 27 days post treatment, he elected to withdraw
completely from the study. His hematology values at that time were: herno-
globin 10.2, hematocrit 32%, RBC 3.56, WBC 1.100 (6% polys, 88% lymphs,
6% monos), reticulocytes 0.4%. platelets 35,600, sedimentation rate 75 mm.
He expired February 6, 1964. No autopsy was obtained.
- 29 -
220- n W F 2 200- - n - 0
180- n z I 160- a E 0
0 I
140- - 120-
100 -
Fig. 1 QUANTITATIVE PRECIPITIN TEST # 030
J. D.
I I I I I I I
0 8 16 24 32 40 48 8 PRE Rx I POST Rx
DAYS
Fig. 2 PRINTOUT OF TOTAL WHITE COUNT- NO PREVIOUS THERAPY, LOW DOSE
NO PREV., LOW WSE .............................................................................................
1.400 <
1.200 <
1.000 -; .
T W I
C E S
1
B M o.eoo+
0.600 -:
0.400 4
0.200 <
.............................................................................................. 0. 5.00 10.00 15.00 20.00 25.00 30 .oo
T I M E S I 51 PIECES OF DATA GRAPHED DAY NO..
0. I
DISTRIBUTION
ARMY AGMCIES
Deputy C h i e f of S t a f f f o r Mi l i t a ry Operations, Department of t h e Army, A m : D i r
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Unclassified
University of Cincinnati College of Medicine Cincinnat i , Ohio 45229
Security Clissifiution DOCUMENT CONTROL DATA- R6D 1
Unclassified a b OIOUP ---
d.
Annual Report - 1 b y 1863 t o 29 February 1864 I. AUTWOIW IUS. fin: nrr, m i u d I
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Saenger, Eugene L., Y.D.; Friedman, Ban I . , Y.D.; Kerei.kea, James Q . , Ph.D.; Perry, Rmrold, Y.D.
I . nEcoRT DATE 17.. I 0 I . L *o. o r ..=e. I 7 b MO 0 1 1 ~ ~ . 1
M-49-146-XZ-029
A&-03. OM) A CROJCCI Yo.
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This repor t has been apprwdd f o r open publ icat ion by t h e Department of Defense , Qualified requemters may obtain copies of this repor t frcm DE. 1. L U P P L L Y C Y T A I Y M O T I S 12. SPOWSOIIMG MILITARY ACTlVlTV
Defense Atapic Support Agency Washington, D. C. 20301
1. A.CTRACT These s t u d i e s are designed t o obtain information which is necessary t o estimt
caubat e f fec t iveness of t roops and t o develop methods of diagnosis , prognosis, prophylaxis and treatment of rad ia t ion In jury . A t t h e present time parameters of a c t i v e inves t iga t ion a r e c l in i ca l f indings, hematologic e f f e c t s , p r o f i l e acorea, miscellaneous laboratory tests, deoxycytidine excret ion i n t h e ur ine , xanthurenic a c i d excret ion i n the ur ine , chromosome changes i n leucocyter, immunologic s t u d i e s and t h e use of autologous bone marrow.
from a Cog' source. Only one of the p a t i e n t s had prodromrl nauses and v m l t i n g with nausea l a s t i n g 48 hours. Tne lwest hematologic values w e r e found 25 t o 35 days a f t e r I r r a d i a t i o n .
t o t a l body i r r a d i a t i o n , I n rats much larger amounta w a r e found i n the ur ine a f t e r 500r and 800r whole body i r r a d i a t i o n than a f t e r lesser doses.
Studiec by Dr. Anthony Luzzio, U . S . Army Research Laboratory, F t . Knox, Kentucky, i n d i c a t e there may be an immunologic post i r r a d i a t i o n a l t e r a t i o n i n human p m m a globul in an t igenic i ty .
Conba t e f fec t iveness would be r e l a t i v e l y maintained with an exposure up t o 200 rad, though a second exposure wculd r e s u l t i n s i g n i f i c a n t t roop inef fec t iveness .
S ix a t i e n t s were given f r m 149r t o 2311- (100-150 rad) t o t a l body i r r a d i a t i o n
Dcaxcytidine was found i n increased amounts i n the ur ine frm p a t i e n t s a f t e r
Unclassified Securitv Classificanon
Uncloclrifled Security Classification
I I. I K E Y WORDS
I r r a d i a t i o n of human pPtieIItS Metabolic than-8 Tota l body i r r a d i a t i o n Hematologic e f f e c t s Deoxycytidine excretion Chromosome changer Endoreduplication Immunologic s t u d i e s
Unclassif ied Security Classification
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