Louis H. Hempelmann

THE ACUTE RADIATION SYNDROME: A STUDY OF NINE CASES AND A REVIEW OF THE PROBLEM

Excerpt A collaborative clinical investigation by the following members (or former members) of the Los Alamos Scientific Laboratory and the Argonne National Laboratory: J. Garrott Allen Norman P. K...

Risk of Thyroid Neoplasms after Irradiation in Childhood Studies of populations exposed to radiation in childhood show a dose response over a wide dose range

The incidence of thyroid carcinoma and of clinically palpable thyroid nodules is compared in three groups of individuals many years after exposure to ionizing radiation in childhood or infancy. The estimated mean cumulative doses to the thyroid gland ranged from 20 rad in the Ann Arbor series irradiated with x-rays as infants for thymic enlargement upward to 1225 rad of mixed radiation (including that from ingested radioiodine) in the Marshallese children. Intermediate between these extremes is the high-risk subgroup in the Rochester series of persons irradiated for thymic enlargement; they received an estimated mean thyroid dose of 335 rad. A plot of the incidence of thyroid nodularity against the total cumulative thyroid dose gives what could be a linear dose response with no threshold or, at least, a threshold below 20 rad. The risk of developing carcinoma in the three studies ranges from 0 to 5.5 cases and that for nodularity 38 to 52 cases per 106 persons exposed per rad (thyroid dose) per year. There is evidence dence from animal experimentation that the biologically effective dose in the case of the Marshallese would have been considerably lower than the cumulative physical dose; hence, the dose response might actually be curvilinear at least in the higher dose range. In view of the uncertainties regarding dose and the assumptions made in my study, the risk values may not be exact; however, these values reflect the trends regarding risks estimated from the best available data in man. Furthermore, the estimated risk values apply only if radiation exposure occurred in childhood.

Risk of extrathyroid tumors following radiation treatment in infancy for thymic enlargement.

Two thousand eight hundred and fifty-six individuals who received X-ray treatments in infancy for an enlarged thymus gland and their 5053 nonirradiated siblings have been followed prospectively since 1953 to evaluate the risk of radiation-induced neoplastic disease. The health status of the entire cohort has been ascertained periodically by mail questionnaire survey. Based on the cumulative experience of five surveys of this cohort, the irradiated group has a statistically significant increased risk for both benign and malignant extrathyroid tumors, the age-adjusted relative risks being 2.0 and 2.2, respectively. Benign tumors of the bone, nervous system, salivary gland, skin, and breast (females only) and malignant tumors of the skin and breast (females only) account for the excess incidence of extrathyroid tumors among the thymic-irradiated individuals. Although a radiation-induced excess of extrathyroid tumors was suggested in an earlier survey of this cohort, small numbers restricted attribution of this excess to specific sites. The implications of these findings are discussed. Thyroid tumors are addressed in a separate paper.

THE EFFECT OF IONIZING RADIATION ON DEOXYRIBONUCLEASE ACTIVITIES OF BODY FLUIDS. I. THE EFFECT OF TOTAL BODY EXPOSURE ON THE URINARY EXCRETION OF DEOXYRIBONUCLEASES

Abstract 1. 1. Some of the properties of urinary DNases of the rat have been described. 2. 2. It has been shown that there is increased acid and neutral DNase activity in the urine of rats exposed to total body x-rays.

METHODOLOGICAL PROBLEMS AND DESIGN OF THE TRISTATE LEUKEMIA SURVEY

The research described here was designed to test as many as possible of the hypotheses relating to the epidemiology of leukemia. Previous studies have suggested that leukemia patients differ from other populations on several variables : social class, race, nationality background, religion, familial aggregation of leukemia, radiation exposure, history of illness, immunizations, hospitalization, sulfa therapy, factors relating to childbirth, and congenital malformations. For example, Hewitt,l using data of the English Registrar-General, found the upper class rate of leukemia to be twice that of the lower classes. MacMahon and Koller2 found Russian-Americans to comprise about 40 per cent of the leukemia population and only 26.2 per cent of the general population of Brooklyn. They also found it to occur twice as frequently among Jews, native and foreign born, of all ages and sexes, as among others. A number of studies, for example, those by Lange et ~ 1 . ~ Stewart? and most recently by Manning,5 have found relationships of various magnitudes with radiation history, including radiation in utero. Our research was designed to examine these and other relationships which have been suggested for leukemia. We were concerned with both acute and chronic leukemia, in both children and adults. Because of the comparatively low incidence of the disease, and the large number of relationships we wished to examine, we chose a large base population for retrospective study. Taking a conservative estimate of incidence, about 6 per 100,000, we determined that in base populations comprising most of New York State outside New York City, and the Baltimore and MinneapolisSt. Paul metropolitan and surrounding rural areas, there would be reported about 1750 leukemia cases over approximately four years, about 350 of whom would be children. The child and adult cases were to be compared to three different kinds of control groups. The first consisted of the siblings of cases. Such a comparison, of course, has the effect of matching on all the factors which in a family group are homogeneous: social class, ethnic background, race, religion, and often even quality of medical care, including

The effect of ionizing radiation on deoxyribonuclease activities of body fluids. II. The plasma DNases after total body irradiation

Abstract 1. 1. The activity of DNase I (pH optimum 7.5) and DNase II (pH optimum 5.6) is markedly elevated in the plasma of irradiated rats. 2. 2. The maximum activity of DNase I occurs 6 days after exposure whereas the peak activity of DNase II occurs 1 day after exposure.

Synergism between radiation and other risk factors for breast cancer

Abstract The question of whether the risk of radiation-induced breast cancer is additive or multiplicative (synergistic) with other risk factors for breast cancer has important implications for determining optimal guidelines for mammographic screening. Data from a follow-up study of 571 women given X-ray therapy for acute postpartum mastitis in Rochester, New York, and 993 control women were analyzed to examine this question. No synergism was found between breast irradiation and family history of breast cancer, late parity, oral contraceptive use, menopausal hormone use, or a composite of ovarian-related factors. Results indicated that women with a history of breast irradiation who develop benign breast disease, particularly cystic disease, are at high risk for breast cancer and should be carefully monitored. Women who were irradiated at the time of their first childbirth are also at especially high risk for breast cancer.

Radiation and Host Factors in Human Thyroid Tumors Following Thymus Irradiation

Abstract In this paper thyroid tumor data from the 1971 survey of the Rochester, New York thymus irradiated population are further analyzed to study radiobiological and host factors. The analyses were based on the approx. 2650 irradiated subjects and 4800 sibling controls who had 5 or more years of follow-up. Twenty-four thyroid cancers and 52 thyroid adenomas were found in the irradiated group, and 0 thyroid cancers and 6 adenomas among the controls. The overall risk estimates were 3.8 thyroid cancers/106 PY-rad and 4.5 thyroid adenomas/106 PY-rad. The dose-response data (thyroid dose range of 5 to > 1000 rad) for thyroid cancer indicate both a linear and a dose-squared component, but no dose-squared component is evident for thyroid adenomas. At lower total doses (< 400 rad) there was a suggestion that dose fractionation diminished the thyroid cancer response, but a similar fractionation effect was not found for thyroid adenomas. The temporal pattern of tumors suggested an extended plateau of excess tumor production, rather than a “wavelike” temporal pattern. There was no evidence for an inverse relationship between thyroid radiation dose and thyroid cancer latency. Female and Jewish subjects had a higher risk of radiation-induced thyroid cancer than did their respective counterparts. The additive and multiplicative models of radiation effects were compared with respect to sex differences; neither model provided a superior fit to the data. The tentative nature of the conclusions is stressed because of the relatively small number of thyroid cancers.

Dose Dependency of Radiation-Induced Creatine Excretion in Rat Urine

Creatine excretion in urine of rats after whole-body exposure to various doses of x rays (25 to 1000 r) and after sham-irradiation was determined. Although creatinuria was observed at all levels of exposure, the degree was dependent on the dose. Creatinuria lasted from 3 to 16 days after exposure. In the intermediate dose range a second rise in the excretion of creatine was observed during the second week after exposure. The average creatine excretion during the initial 4 days after exposure varied linearly with the dose up to 650 r.

Studies on the Metabolism of Tissue Proteins: III. The Turnover of Soluble Proteins and Elastin Labelled with 14C proline and its Relation to Exposure to Total-body X-irradiation

SummaryRats were injected with proline-U-14C and exposed to total-body x-irradiation at various time-intervals thereafter. Proline was isolated from the soluble protein and elastin fractions of various organs and its specific activity determined. In most organs an increase in specific activity of proline of these two protein fractions was observed after irradiation. This was interpreted to mean either a lowered metabolic replacement or a loss of certain components from these protein fractions after irradiation. It is suggested that the decrease in specific activity observed in the spleen is correlated to changes in the cell-population in this organ after irradiation.