Ultrasound-detected thyroid nodule prevalence and radiation dose from fallout.

Settlements near the Semipalatinsk Test Site (SNTS) in northeastern Kazakhstan were exposed to radioactive fallout during 1949-1962. Thyroid disease prevalence among 2994 residents of eight villages was ascertained by ultrasound screening. Malignancy was determined by cytopathology. Individual thyroid doses from external and internal radiation sources were reconstructed from fallout deposition patterns, residential histories and diet, including childhood milk consumption. Point estimates of individual external and internal dose averaged 0.04 Gy (range 0-0.65) and 0.31 Gy (0-9.6), respectively, with a Pearson correlation coefficient of 0.46. Ultrasound-detected thyroid nodule prevalence was 18% and 39% among males and females, respectively. It was significantly and independently associated with both external and internal dose, the main study finding. The estimated relative biological effectiveness of internal compared to external radiation dose was 0.33, with 95% confidence bounds of 0.09-3.11. Prevalence of papillary cancer was 0.9% and was not significantly associated with radiation dose. In terms of excess relative risk per unit dose, our dose-response findings for nodule prevalence are comparable to those from populations exposed to medical X rays and to acute radiation from the Hiroshima and Nagasaki atomic bombings.

Reproducibility and validity of radioimmunoassays for urinary hormones and metabolites in pre- and postmenopausal women.

The reproducibility of RIAs of circulating sex hormones has been evaluated as part of recent epidemiological investigations, but none seem to have addressed the reproducibility or validity of RIAs for urinary hormones or their metabolites. As part of a case-control study of breast cancer in Asian-American women, 12-h overnight urine samples were obtained, and a methodological study was conducted to identify laboratories capable of assaying urinary hormones. For the reproducibility component of this study, two laboratories with extensive experience in hormone assays measured urinary estrone, estradiol, estriol, pregnanediol glucuronide, and estrone glucuronide using samples from 15 women (5 midfollicular, 5 midluteal, and 5 postmenopausal). Variance estimates from these measurements were used to calculate the laboratory variability (coefficient of variation) and to assess the magnitude of the biological variability among the women in relation to the total variability (intraclass correlation coefficient). For the validity component, urinary estrone, estradiol, and estriol levels were measured in the same samples by gas chromatography-mass spectroscopy in the laboratory of Dr. Herman Adlercreutz (University of Helsinki, Helsinki, Finland). We found that the degree of assay reproducibility differed between the laboratories, but that laboratory variability was usually low compared with the range of hormone values among women, particularly for the estrogens. Values for estrone and estradiol were well correlated among all of the laboratories. For estriol, the RIAs tended to overestimate levels compared with gas chromatography-mass spectroscopy. In one laboratory, assays for pregnanediol glucuronide and estrone glucuronide were consistently reproduced; in the other, the reproducibility of the RIA for pregnanediol glucuronide was problematic, and estrone glucuronide was not measured. Despite some limitations, urinary hormones and their metabolites can be reliably measured by current RIAs in large investigations attempting to link hormone level to disease risk and may be particularly advantageous for studies of postmenopausal women, where serum concentrations of estrone and estradiol are low and assay measurements are not as dependable.

Insulin-like growth factors and prostate cancer: a population-based case-control study in China.

Insulin-like growth factors (IGFs) have potent mitogenic and antiapoptotic effects on prostate epithelial cells. Through modulation of IGF bioactivity and other mechanisms, IGF-binding proteins (IGFBPs) also have growth-regulatory effects on prostate cells. Recently, IGF-I and IGFBP-3 have been implicated in prostate cancer risk among Western populations. To assess whether IGF-I, IGF-II, IGFBP-1, or IGFBP-3 are also associated with prostate cancer in a low-risk population, we measured plasma levels of these factors among 128 newly diagnosed prostate cancer cases and 306 randomly selected population controls in Shanghai, China. Relative to the lowest quartile of IGF-I levels, men in the highest quartile had a 2.6-fold higher prostate cancer risk, with a significant trend [odds ratio (OR) = 2.63; 95% confidence interval (95% CI) = 1.19-5.79; P(trend) = 0.01]. In contrast, men in the highest quartile of IGFBP-3 levels had a 46% decreased risk relative to the lowest quartile (OR = 0.54; 95% CI = 0.26-1.15; P(trend) = 0.08). A similar but less distinct result was observed for IGFBP-1 (OR = 0.60; 95% CI = 0.31-1.17; P(trend) = 0.25). Men in the highest quartile for the IGF-I:IGFBP-3 molar ratio (an indirect measure of free IGF-I) had a 2.5-fold higher risk compared with the lowest quartile (OR = 2.51; 95% CI = 1.32-4.75, P(trend) < 0.001). These associations were more pronounced after adjustment for serum 5alpha-androstane-3alpha,17beta-diol glucuronide and sex hormone-binding globulin levels. There was no significant association with IGF-II levels. Our findings in a low-risk population provide evidence that IGF-I, IGFBP-3, and IGFBP-1 are determinants of prostate cancer and indicate that additional studies are needed to evaluate their effects on ethnic and geographic incidence differentials and to elucidate carcinogenic mechanisms.

Persistently low blood retinol levels during and after parenteral feeding of very low birth weight infants: examination of losses into intravenous administration sets and a method of prevention by addition to a lipid emulsion.

Very low birth weight infants have little storage of hepatic retinol and are, therefore, highly dependent upon an exogenous supply. The recent association between low serum retinol level and bronchopulmonary dysplasia and the persistently low serum levels of retinol during total parenteral nutrition prompted a prospective study to evaluate serial changes in serum retinol levels during 1 month of total parenteral nutrition (retinol dose 455 micrograms/d) and again during 1 month of total enteral feeding (retinol dose 200 to 300 micrograms/d) in the same infants. Infants were divided into two groups. Group 1 consisted of infants weighing less than 1,000 g (n = 24) and group 2 consisted of infants weighing 1,000 to 1,500 g (n = 17). Although initial mean levels of retinol were similar in both groups (14.8 +/- 0.9 and 13.5 +/- 0.7 micrograms/dL), there was wide variation between infants. In group 1 infants, there was a significant (P less than .01) decline in retinol level by the second week of life (to 9.2 +/- 1 micrograms/dL), which persisted during total parenteral nutrition, but increased to 13.4 +/- 2 after 1 week of enteral feeding. This level was maintained throughout enteral feeding. In group 2 infants, there was no significant change in serum retinol level throughout the study. During total parenteral nutrition, several infants had retinol levels below 10 micrograms/dL, a level associated with signs of retinol deficiency in older children. Because losses of retinol are known to occur in smaller volume total parenteral nutrition solutions, it was speculated that losses of retinol in our patients were due to retinol losses in the total parenteral nutrition delivery system.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantifying estrogen metabolism: an evaluation of the reproducibility and validity of enzyme immunoassays for 2-hydroxyestrone and 16alpha-hydroxyestrone in urine.

Rapid and simple enzyme immunoassays (EIAs) were recently developed to measure 2-hydroxyestrone and 16alpha-hydroxyestrone in unextracted urine. The balance between these competing estrogen metabolism pathways may serve as a biomarker of breast cancer risk. Before testing these assays in epidemiologic studies, we evaluated their reproducibility, and validity relative to gas chromatography-mass spectroscopy (GC-MS). Overnight 12-hr urine collections from five midfollicular premenopausal women, five midluteal premenopausal women, and five postmenopausal women were aliquoted and stored at -70 degrees C. Two aliquots from each woman were assayed with the EIAs in a random, blinded order, monthly over 4 months and 1 year later. Reproducibility over 4 months was good for both metabolites in premenopausal women (coefficient of variation = 8-14%) and satisfactory in postmenopausal women (approximately 19%). Reproducibility over 12 months remained good in premenopausal women, but was poor in postmenopausal women, with mean readings increasing 50 to 100%. Wide variation in estrogen metabolite levels enabled a single EIA measurement to characterize individual differences among premenopausal women in midfollicular (intraclass correlation coefficient = 98-99%) and midluteal phase (85-91%). A narrower range in metabolite levels among postmenopausal women reduced discrimination (78-82%). The correlation between EIA and GC-MS measurement was excellent for both metabolites (r>0.9), except for 2-hydroxyestrone in postmenopausal women (r=0.6). Analysis of absolute agreement suggested that both EIAs were less sensitive than GC-MS, and each detected nonspecific background. The low concentration of estrogen metabolites in urine from postmenopausal women may explain the problems with reproducibility and validity in this menstrual group. Accordingly, more sensitive EIAs have been developed and are now being evaluated.

Nutrition and dietary supplements.

Quality and number of subjects in blinded controlled clinical trials about the nutrition and dietary supplements discussed here is variable. Glucosamine sulfate and chondroitin sulfate have sufficient controlled trials to warrant their use in osteoarthritis, having less side effects than currently used nonsteroidal anti-inflammatory drugs, and are the only treatment shown to prevent progression of the disease. Dietary supplements of ephedrine plus caffeine for weight loss (weight loss being the current first line recommendation of physicians for osteoporosis) show some promise, but are not sufficient in number of study subjects. Phenylpropanolamine is proven successful in weight loss. Both ephedrine and phenylpropanolamine have resulted in deaths and hence are worrisome [table: see text] as an over-the-counter dietary supplement. Other commonly used weight loss supplements like Cola acuminata, dwarf elder, Yohimbine, and Garcinia camborgia are either lacking controlled clinical trials, or in the case of the last two supplements, have clinical trials showing lack of effectiveness (although Garcinia has been successful in trials as part of a mixture with other substances, it is unclear if it was a necessary part of the mixture). Safety of these weight loss supplements is unknown. Chromium as a body building supplement for athletes appears to have no efficacy. Creatine may help more in weight lifting than sprinting, but insufficient study subjects and safety information make more studies necessary. Carbohydrate loading is used commonly before endurance competitions, but may be underused as it may be beneficial for other sport performances. Supplements for muscle injury or cramps have had too few studies to determine efficacy. Although proper rehydration with fluids and electrolytes is necessary, a paucity of actual studies to maximize prophylactic treatment for exercise induced cramping still exists. Nutritional supplements for cardiovascular disorders are generally geared to prevention. The United States Department of Agriculture has good recommendations to prevent atherosclerosis; a stricter version by Ornish was shown to reverse coronary heart disease, and the low meat, high fruit, and vegetable DASH diet has been found to decrease hypertension. The epidemiologic studies of hyperhomocysteinemia are impressive enough to give folic acid (or vitamin B6 or B12) supplements to those with elevated homocysteine levels and test patients who have a history of atherosclerotic disease, but no controlled clinical trials have been completed. Soluble fiber has several positive studies in reduction of cholesterol levels and generally is accepted. The data on vitamin E are the most confusing. This vitamin was not helpful in cerebrovascular prevention in China and not helpful at relatively small doses (50 mg) in the United States or Finland against major coronary events. Levels of 400 mg appeared to decrease cardiovascular disease in the United States in studies based on reports by patients and in one large clinical trial. Vitamin E also was successful in prevention of restenosis after PTCA in one clinical trial. Both of these clinical trials need to be repeated in other developed country populations. Some nutritional and dietary supplements are justifiably useful at this point in time. Several meet the criteria of a late Phase 3 FDA clinical trial (where it would be released for public use), but many dietary supplements have insufficient numbers of studies. Some deaths also have occurred with some supplements. If these supplements were required to undergo clinical trials necessary for a new drug by the FDA, they would not be released yet to the public. Several nontoxic supplements appear promising, though need further study. Because they have essentially no toxicity (such as folic acid with B12, soluble fiber, and vitamin E) and may have efficacy, some of these supplementations may be useful now, without randomized clinical trials.

A cholinesterase testing program for pesticide applicators.

Illnesses associated with the increased use of cholinesterase-inhibiting pesticides have brought about recommendations for monitoring pesticide applicators. The State of California requires medical supervision; however, the supervision and monitoring guidelines are often incorrectly followed. In this retrospective cohort study, 103 worker-years of cholinesterase monitoring are reported. Twenty-four (24%) workers were temporarily removed from spraying (five were removed twice) because their cholinesterase plasma activity levels were below 60% of baseline. Five workers (5%) had mild symptoms of toxicity but none reported a specific incident of exposure. Hispanic workers had fewer significant drops in plasma activity levels and fewer toxic symptoms than white workers. The relative risk of pesticide poisoning was increased in workers whose initial baseline plasma levels were low or if their levels had already dropped to 60%-80% of their baseline previously in the season. Case studies and differences in baselines by month of determination suggest poor monitoring compliance by the companies and employees. Suggestions of how the physician can overcome these problems and improvements of the guidelines are discussed.

Cancer mortality in women with probable exposure to silica: a death certificate study in 24 states of the U.S.

BACKGROUND: Silica exposure is known to cause an increased risk of pneumoconiosis and some types of cancers. Exposure to silica is becoming an increasingly common occupational hazard for women. Studies contradict each other on whether or not women suffer more occupational pneumoconiosis than men, but no studies have evaluated cancer risks among women exposed to silica. METHODS: Death certificate data on occupation and industry from 24 states in the U.S. between 1984 and 1993 were used to calculate proportional mortality ratios (PMRs) for workers exposed to silica. RESULTS: Over 20,000 deaths (4% of all deaths in persons with possible work-related silica-exposure) occurred among women. The PMR for pneumoconiosis among women working in occupations or industries with possible silica exposure was 13.6 (95% CI: 7.2-23.2), for men 3.8 (CI: 3.7-4.0). Both men and women had higher than expected PMRs for respiratory diseases, lung and esophageal cancers, and external causes of death. In the group with probable silica exposure (both occupation and industry associated with silica), women had elevated PMRs for thyroid cancer (PMR = 5.5), multiple myeloma (PMR = 1.3), digestive organ cancers (PMR = 1.2), whereas men had no increased PMRs for these cancers. Both genders had significantly decreased PMRs for breast cancer, cerebrovascular diseases, nervous system diseases, and brain and other central nervous system cancers. CONCLUSIONS: An in depth look at the types of silica exposures (specific work duties) and adjustment for confounders is warranted to determine the importance of these gender-specific excess mortalities associated with possible silica exposure.