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Biomedical subjects

R E Shore

Publications and source records attributed to R E Shore.

At least 73 records · Page 4Linked to original sources

Overview of radiation-induced skin cancer in humans.

There are about a dozen studies of the incidence of skin cancer among irradiated populations with known skin doses that are available for estimating the risk of radiation-induced skin cancer. It is of note that they provide no evidence for a dose threshold and are compatible with a linear dose-response relationship, at least for ultraviolet radiation exposed skin. The studies also provide varying amounts of evidence concerning a number of other important issues in assessing skin cancer risk: types of skin cancer induced by ionizing radiation, the appropriateness of relative risk vs absolute risk models, combined effects of ionizing and UV radiations, and variations in sensitivity to skin cancer induction among demographic and genetic subgroups. Little epidemiological information is available on several factors, such as the RBE for high-LET radiation, the effects of dose protraction or fractionation, or variations in risk by age at irradiation. A reasonable estimate of skin cancer lethality was 0.2 per cent when weighted for the relative proportions of squamous cell and basal cell skin cancers. Average risk estimates of radiation-induced skin cancer incidence were: absolute risk (AR) of 8.5 X 10(-4) person-year-Sv and excess relative risk (RR) of 52 per cent/Sv. Lifetime skin cancer risk was calculated by life-table methods for males from exposures spread out over ages 20-60 years. The estimates for excess skin cancer incidence were 2 per cent and 11 per cent per Sv under the AR and RR models, respectively, while the corresponding mortality risks were 4 X 10(-5) and 2 X 10(-4) per Sv.

Environmental Exposure↗

Occupational radiation studies: status, problems, and prospects.

At least 350,000 workers at U.S. radiation facilities are being followed up to monitor their mortality experience, with particular reference to cancer. Although these studies are expensive, they are needed from the standpoint of public health and radiation protection; they also provide a useful check that the risk extrapolation models based on high dose data are not seriously out of line. Unfortunately, there are a number of problems in interpreting radiation worker studies that stem mainly from the fact that the expected magnitude of effects is small because of the low doses. Problems of falsely positive effects caused by chance or by study biases are difficult to distinguish from real effects. Dose-effect analyses and pooled analyses from several studies offer some improvements in assessing the risk from low doses but do not obviate all the problems. Future studies should explore whether there are biological markers of exposure, damage, or susceptibility that would improve our power to assess individual risk.

Dose-Response Relationship, Radiation↗

Men assigned to ethylene oxide production or other ethylene oxide related chemical manufacturing: a mortality study.

A retrospective cohort study was conducted to examine the mortality experience of 2174 men employed between 1940 and 1978 by a large chemical company and who had been assigned to a chemical production department that used or produced ethylene oxide (EO). Comparisons were made with the general United States population, the regional population, and with a group of 26,965 unexposed men from the same plants. Comparisons with general United States death rates showed fewer deaths than expected in the EO group due to all causes and for total cancers. There was no statistically significant excess of deaths due to any cause. Seven deaths each due to leukaemia and pancreatic cancer were observed with 3.0 and 4.1 deaths expected. Among the subcohort of men who worked where both average and peak exposure levels were probably highest, however, one death due to pancreatic cancer (0.9 expected) and no deaths due to leukaemia were observed. Four of the seven who died from leukaemia and six of the seven who died from pancreatic cancer had been assigned to the chlorohydrin department where the potential for exposure to EO is judged to have been low. The relative risk of death due to each disease was strongly related to duration of assignments to that department. When men who worked in the chlorohydrin department were excluded, there was no evidence for an association of exposure to EO with pancreatic cancer or leukaemia. Together with the failure to show independent EO associations, the chlorohydrin department results suggest that leukaemia and pancreatic cancer may have been associated primarily with production of ethylene chlorohydrin or propylene chlorohydrin, or both. These results emphasise the importance of examining additional concurrent/asynchronous exposures among human populations exposed to EO.

Adult↗

The risk of breast cancer after irradiation of the thymus in infancy.

It is well established that exposure to ionizing radiation during or after puberty increases a woman's risk for breast cancer, but it is less clear whether exposure to ionizing radiation very early in life is also carcinogenic. We studied the incidence of breast cancer prospectively in a cohort of 1201 women who received x-ray treatment in infancy for an enlarged thymus gland and in their 2469 nonirradiated sisters. After an average of 36 years of follow-up, there were 22 breast cancers in the irradiated group and 12 among their sisters, yielding an adjusted rate ratio of 3.6 (95 percent confidence interval, 1.8 to 7.3). The estimated mean absorbed dose of radiation to the breast was 0.69 Gy. The first breast cancer was diagnosed 28 years after irradiation. The dose-response relation was linear (P less than 0.0001), with a relative risk of 3.48 for 1 Gy of radiation (95 percent confidence interval, 2.1 to 6.2) and an additive excess risk of 5.7 per 10(4) person-years per gray (95 percent confidence interval, 2.9 to 9.5). We conclude that exposure of the female breast to ionizing radiation in infancy increases the risk of breast cancer later in life.

Adult↗

Radiation epidemiology: old and new challenges.

Over the last 40 years the amount of knowledge about human radiation effects has increased dramatically. During that interval, radiation epidemiologists have documented a number of additional types of radiation-induced cancer and have established rough estimates of the magnitude of cancer risks. Nevertheless, we currently have inadequate knowledge about a number of factors that help define the magnitude of radiation risks. These include questions of estimating risk over the lifetime, shapes of dose-effect curves, magnitude of risks at low doses, potentiation between radiation and other agents, and the nature and role of host susceptibility factors. Data from various studies are used to illustrate these questions.

Adult↗

The potential role of nutritional factors in the induction of immunologic abnormalities in HIV-positive homosexual men.

The literature is briefly summarized as to how several nutrients affect immune function, susceptibility to infection, and cancer susceptibility or progression. Nutritional deficiencies can impair immunity and so influence susceptibility to infectious agents, including ones that are common and relatively virulent in acquired immune deficiency syndrome (AIDS) patients. A variety of nutrients affect several of the immune functions that are defective in human immunodeficiency virus (HIV)-infected individuals. For example, beta-carotene increased the number of CD4+ cells; vitamin E decreased the number of CD8+ cells and increased the CD4+/CD8+ ratio; vitamin D decreased the CD4+/CD8+ ratio; and iron increased the number of peripheral lymphocytes in humans receiving supplementation. Furthermore, nutritional deficiencies can influence gastrointestinal function, while infectious diseases can influence nutrient requirements by altering the efficiency of absorption and the rate of tissue metabolism. Malnutrition, depressed serum zinc levels, and intestinal nutrient malabsorption have been found in AIDS patients. The above findings suggest that dietary manipulations might diminish the immune defects in HIV infection and enhance resistance to opportunistic infections. However, dietary alterations in immune defects are generally not well quantified and may be small relative to the magnitude of the defects observed in AIDS patients. Because conflicting or adverse effects have been reported for some nutrients, recommendations for dietary supplementation in HIV-infected individuals are premature and possibly hazardous. Further studies are much needed to relate dietary nutrient intakes to clinical outcomes.

HIV Seropositivity↗

Electromagnetic radiations and cancer. Cause and prevention.

The various types of electromagnetic radiation differ considerably in their ability to induce cancer. The potential of radiofrequency or microwave radiation and low-frequency electromagnetic radiation to alter DNA is very limited, because their energy is too low to produce substantial ionizations. They are therefore unlikely to be carcinogenic by any direct mechanism. Epidemiologic studies of the carcinogenicity of microwave radiation are basically negative. Studies of workers with relatively high exposures to low-frequency electromagnetic fields have suggested that such persons may be at somewhat elevated risk for leukemia, especially of the acute myeloid type, but the studies have had methodologic weaknesses and mixed results. The association is not proven at this point, but neither can it be ruled out. For ionizing radiation, which is clearly carcinogenic, major questions pertain to how to define the magnitude of risk from low doses and low dose rates, how to identify subgroups of people who are especially susceptible to the effects of ionizing radiation, and how to minimize radiation exposure. When fortuitous radiation exposure from manmade sources, such as radioactive releases from nuclear power plants, are examined in the context of the total exposure people receive from natural sources, medical irradiation, etc., they are almost always found to be small by comparison. Quantitatively, two sources of radiation provide the greatest opportunities for exposure reduction: abatement of radon levels in homes, and reduction in medical radiation exposures.

Electromagnetic Fields↗

Applications of epidemiologic methods to podiatric medicine.

National statistics show that the burden of occupational foot problems is large. For example, over 20 per cent of work-related injuries occur in the lower extremities. However, to date few epidemiologic studies have been undertaken to document the nature, frequency, and causes of occupational foot problems. More are clearly needed. The results of such studies could profitably be disseminated among occupational health professionals to increase their awareness of this relatively neglected aspect of worker health.

Epidemiologic Methods↗

An industry-wide study of respiratory cancer in chemical workers exposed to chloromethyl ethers.

An industry-wide retrospective cohort mortality study was conducted on 6,152 chemical workers (2,460 exposed and 3,692 nonexposed) engaged in chloromethyl ether manufacture at 7 major U.S. companies between 1948 and 1980. A previous study at 6 companies from 1948 through 1972 reported excess respiratory cancer (RC) mortality and significant exposure-response relationships in exposed workers at 1 company (company 2). The present study, which extended follow-up of an additional 7 years for companies 1-6 and included company 7 for follow-up from 1953 through 1980, found excess RC mortality in exposed workers at company 2 [observed (Obs) = 32, standardized mortality ratio (SMR) = 430] and company 7 (Obs = 9, SMR = 603). External comparisons of RC mortality at both companies showed significant exposure-response relationships with respect to cumulative time-weighted exposure. At company 2, where the greatest number of RC deaths occurred, external comparisons showed that RC risk remained constant in relation to age at first exposure and decreased with increasing time since last exposure. With the use of Mantel-Haenszel and relative risk (RR) regression methods, internal comparisons at company 2 demonstrated significant findings of increasing RR with cumulative duration of exposure and cumulative time-weighted exposure and with decreasing time since last exposure. No association was found between RR and age at first exposure. An interesting finding was a significant negative interaction between cumulative time-weighted exposure and age at risk. The best-fitting logistic regression model for the exposed group predicted RR at 2.79 (95% confidence interval = 1.66-4.69) for workers with the mean cumulative exposure score of the 32 RC deaths (lagged by 6 yr) compared with those with negligible exposure (assuming mean age at risk of the RC deaths, 51 years old, and time since last exposure held constant). Qualitative assessment of the results suggests that chloromethyl ether exposure affects both an early as well as a late stage of a putative multistage respiratory malignant process.

Adult↗

Breast cancer among women given X-ray therapy for acute postpartum mastitis.

Acute postpartum mastitis (APM) is an inflammatory-infectious condition of the breast, occurring commonly at childbirth or during lactation. A series of 601 women who received x-ray therapy for APM during the 1940's or 1950's have been followed up by mail questionnaire, with medical verification of pertinent conditions, to ascertain their incidences of breast cancer. Control subjects consisted of a series with APM who did not receive irradiation, plus the female siblings of both the APM groups, for a total of 1,239 controls. The groups have been followed up to 45 years; the average was 29 years. The relative risk (RR) for breast cancer, adjusted for age and interval since irradiation (or an equivalent entry definition for controls), was 3.2 for the irradiated breasts; the 90% confidence interval (CI) was 2.3-4.3. For a linear multiplicative model, the risk increased by 0.4% per rad (90% Cl of 0.2-0.7). The dose-response curve appeared to be essentially linear, except for a diminution of risk at high doses (greater than or equal to 700 rad). The fact that there were no treated breasts with doses between 0 and 60 rad, however, means that it was not possible to evaluate the curvature with the maximum contrast between low and high doses. The dose fractionation analyses showed that neither the number of dose fractions, the number of days between fractions, nor the dose per fraction had any apparent effect on breast cancer risk when the variables were analyzed separately. Similarly, when the fractionation variables were considered jointly in a Cox regression analysis, none was significant once total breast dose was controlled for. Analyses of age at irradiation did not show appreciable differences between age groups, although the numbers were too small to be clear-cut (only 64 women greater than 34 yr old at irradiation). Other studies have shown diminished risk associated with an older age at irradiation. The lack of diminished risk in this study may occur because during pregnancy and lactation the breasts are under increased proliferative stimulation by hormones, by comparison with the normal condition of breasts at older ages. An analysis of the temporal relationship of radiation to breast cancer showed that the RR did not vary systematically with interval since irradiation, but the absolute risk increased over time. This finding agrees with other studies that have also suggested a better fit for the multiplicative model.

Acute Disease↗

Thyroid tumors following thymus irradiation.

About 2,650 persons who received X-ray treatment for purported enlarged thymuses in infancy and 4,800 sibling controls have been followed by mail questionnaire for an average of 29 years to observe their incidence of thyroid tumors. The follow-up rate in the latest survey was 88% in both groups. The radiation doses to the thyroid gland ranged from 5 to over 1,000 rad, with 62% receiving less than 50 rad. To date 30 thyroid cancers and 59 benign thyroid adenomas have been detected in the irradiated group, as compared with 1 thyroid cancer and 8 adenomas in the control group. The relative risks in the irradiated group were about 45 for thyroid cancer and 15 for benign thyroid adenomas. The dose-response curve for thyroid cancer was essentially linear, although a linear-quadratic curve could not be ruled out. For thyroid adenomas the risk per rad was somewhat greater at lower doses than at high doses. For both thyroid cancers and adenomas the absolute excess risk per rad was two to three times as great in females as males. Within the limitations imposed by the treatment regimens and the sample size, there was no indication of a "sparing" effect due to dose fractionation for either thyroid cancers or adenomas. There was an excess risk for both malignant and benign thyroid tumors for at least 40 years post irradiation. For thyroid cancer the radiogenic risk appeared to be additive with respect to time, rather than the age-specific natural rates of cancer being multiplied.

Adult↗

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.

Adolescent↗

Radiation induced cancer: risk assessment and prevention.

A number of factors have to be considered in defining the cancer risk from ionizing radiation. These include the radiation sensitivity of the target tissue(s), the temporal pattern of risk, the shape of the dose-incidence curve, the effects of low dose rates, host susceptibility factors, and synergism with other environmental exposures. For the population as a whole the largest sources of radiation exposure are natural background radiation and medical/dental radiation. Radiation exposures in the medical field make up the largest volume of occupational exposures as well. Although new technologies offer opportunities to lower exposures, worker training, careful exposure monitoring with remedial feedback, and monitoring to prevent unnecessary radiodiagnostic procedures may be even more important means of reducing radiation exposure. Screening of irradiated populations can serve a useful preventive function, but only for those who have received very high doses.

Dose-Response Relationship, Radiation↗

Skin cancer incidence among children irradiated for ringworm of the scalp.

A series of about 2200 children who received X-ray treatment for ringworm of the scalp (tinea capitis) during the 1940s and 1950s, and a comparable group of 1400 treated without X ray, have been followed by mail questionnaire for an average of 26 years since treatment to tabulate the incidence of skin cancer. The X-ray treatment consisted of 300-380 R to five overlapping fields on the scalp, to cause complete depilation. This delivered doses of 300-600 rad to various portions of the scalp, with lower doses to the skin of the face and neck. In the irradiated group, 41 persons have had one or more basal cell carcinomas of the scalp or face while only three have been diagnosed in controls. There was a high prevalence of multiple skin cancers in the irradiated group (80 lesions among 41 cases). The minimum latent period for radiation-induced skin cancers was long--about 20 years--and this may be attributable to the young age of the population. The skin cancer risk was particularly pronounced on the face, where there would be more UVR exposure in addition to X-ray exposure. Lightness of complexion proved to be an important factor in the skin cancer risk. In addition, skin cancers were found only among caucasians, even though 25% of the study population were blacks. These findings suggest that UVR exposure levels or sensitivity to such exposure interact with ionizing radiation exposure in defining skin cancer risk.

Adolescent↗

Repeated pulmonary function evaluation following bleomycin treatment.

A computerized, nonsurgical, pulmonary function measurement method was tested for sensitivity and utility in detecting the development of fibrosis. Bleomycin, a fibrogenic agent, was intratracheally instilled into male Fisher 344 rats. Respiratory function was monitored in restrained, awake animals before treatment and for the subsequent 4 wk. In the first week, among responders, a significant (p less than 0.05) drop in body weight, tidal volume, and compliance was accompanied by a significant increase in respiratory frequency. Minute volume increased in the second week. Although body weight, tidal volume, and compliance returned to baseline values in the following weeks, respiratory frequency and minute volume remained significantly elevated. With the methods used here, respiratory rate change was the parameter most sensitive to the effects of bleomycin in vivo.

Animals↗

Sample sizes for individually matched case-control studies: a group sequential approach.

This paper proposes the use of group sequential methods to calculate sample sizes for individually matched case-control study designs. A table is presented in which the average sample size required for a group sequential (i.e., multistage) matched pair design is compared to that of the conventional matched pair fixed sample size plan for the usual constant relative risk situation. The table shows that group sequential designs are in general more efficient than fixed sample size plans. Computer simulations showed that group sequential methods yield the appropriate type I and type II error rates not only for matching on a one-to-one basis, but also more generally with multiple matched controls per case. Further simulation studies indicated that there may be only a small loss of power when the matching variable(s) is associated with the probability of exposure but not with the disease. This is shown for both the multistage and fixed sample tests.

Epidemiologic Methods↗