Public preferences for efficiency and racial equity in kidney transplant allocation decisions.
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Adult↗
Biomedical subjects
J Baron
Publications and source records attributed to J Baron.
Long-term hormone replacement therapy and risk of breast cancer in postmenopausal women.
Despite extensive study, concerns remain about a possible association between long-term postmenopausal hormone treatment--particularly use of combination preparations--and risk of breast cancer. The authors evaluated the use of postmenopausal hormone replacement therapy in relation to breast cancer risk in a large multicenter, population-based case-control study. Women with a new diagnosis of breast cancer were identified through statewide tumor registries in Wisconsin, Massachusetts, Maine, and New Hampshire. Controls were randomly selected from population lists in each state. For this analysis of postmenopausal women, data were available from 3,130 breast cancer cases and 3,698 controls interviewed between 1989 and 1991. Replacement hormone use was not associated with breast cancer risk in women who had ever undergone this treatment (relative risk (RR) = 1.05, 95% confidence interval (CI) 0.93-1.18). Among women who had used replacement hormones for 15 years or more, there was no clear increase in risk, although the small sample size did not preclude the possibility of a modest association (RR = 1.11, 95% CI 0.87-1.43). Risk among women using progestins in combination with estrogens was similar to that in women using estrogens alone. Risk did not vary according to type of menopause, family history of breast cancer, history of benign breast disease, or alcohol intake. These results are consistent with the majority of reports which find no overall increased risk associated with the use of replacement hormones. However, in contrast to several other studies, this study did not find long-term use to be associated with increased risk. These results also do not support a hypothesized effect of combined progestin and estrogen use on the risk of breast cancer.
Breast Neoplasms↗
Risk of breast cancer in relation to lifetime alcohol consumption.
BACKGROUND: Although an association between alcohol consumption and risk of breast cancer has been observed in many studies, questions of major importance remain, including the nature of the dose-response relationship and the effects of drinking at various periods in life. PURPOSE: Our goal was to address the issues listed above with a large case-control study. METHODS: We conducted a population-based case-control study in Maine, Massachusetts (excluding the four counties that include metropolitan Boston), New Hampshire, and Wisconsin. Case patients were eligible if their diagnosis of invasive breast cancer was first reported to one of the four statewide cancer registries during the period of 1988 through 1991. During the accrual period, 11,879 potentially eligible case patients and 16,217 control subjects were identified. After excluding ineligible women from the study, telephone interviews were obtained from 6888 case patients and 9424 control subjects. Complete data for recent alcohol consumption, and thus final eligibility for study participation, were determined for 6662 case patients and 9163 control subjects. The average age at time of interview was 58.7 years. The questions on alcohol use addressed average consumption during five periods of the subjects' lives: ages 16-19, 20-29, 30-39, 40-59, and 60-74 years. Similar responses from 211 control subjects upon reinterview 6-12 months later were taken to be indicative of the reliability of the questionnaire used in this study. RESULTS: Lifetime average alcohol consumption (measured as the average grams per day consumed from age 16 to the recent past) and recent alcohol consumption (average grams per day consumed in the previous age interval) were associated with risk of developing breast cancer. The multivariate relative risk of breast cancer, in those who drink compared with abstainers, associated with average lifetime consumption of 12-18 g/day of alcohol (about one drink) was 1.39 (95% confidence interval [CI] = 1.16-1.67), of 19-32 g/day (about two drinks) was 1.69 (95% CI = 1.36-2.10), of 33-45 g/day (about three drinks) was 2.30 (95% CI = 1.51-3.51), and of greater than or equal to 46 g/day (four or more drinks) was 1.75 (95% CI = 1.16-2.64) (P for trend < .0001). The multivariate relative risk per 13 g/day (about one drink) of alcohol consumed before 30 years of age was 1.09 (95% CI = 0.95-1.24), whereas the relative risk associated with recent consumption of 13 g/day was 1.21 (95% CI = 1.09-1.34). CONCLUSIONS: In these data, alcohol consumption was clearly related to breast cancer risk. Risk appeared to increase even at moderate levels of consumption. For women of all ages combined, consumption before 30 years of age was not an important determinant of risk.
Adolescent↗
Organochlorine compounds and estrogen-related cancers in women.
The organochlorines, a diverse group of some 15,000 compounds, have been implicated increasingly as being harmful to humans. Some congeners of DDT and PCB elicit very weak estrogenic responses in animals, while the dioxin TCDD and related compounds have antiestrogenic properties. This review summarizes the evidence regarding whether certain organochlorine compounds, usually as persistent food-chain contaminants, increase the risk of breast and endometrial cancers through their estrogenic potential. In humans, neither ecologic data nor occupational studies provide clear support for an association between organochlorine exposure and the occurrence of these cancers. In our summary analysis of occupational exposure, the rate ratio of breast cancer for exposed cf unexposed women was 0.84 (95 percent confidence interval [CI] = 0.50-1.33) for PCBs and 1.08 (CI = 0.68-1.58) for TCDD. Similarly, effect estimates close to unity were found in summary analysis of breast cancer case-control studies regarding levels of DDE and PCB in adipose tissue or serum. In two recent nested case-control studies using stored specimens, the odds ratio per standard deviation increase in serum p,p'-DDE was 1.27 (CI = 0.95-1.69). Although estrogenic effects of certain organochlorine compounds should be easier to detect on the endometrium, we know of no analytic epidemiologic studies of endometrial cancer published to data. We conclude that available data do not indicate that organochlorines will affect the risk of these two cancers in any but the most unusual situation.
Adipose Tissue↗
Use of ultrasensitive recombinant cell bioassay to measure estrogen levels in women with breast cancer receiving the aromatase inhibitor, letrozole.
The development of well tolerated, potent, specific, and nontoxic aromatase inhibitors for the treatment of postmenopausal women with estrogen-dependent breast cancer has been a major goal of recent studies. The third generation inhibitors now under investigation are nearly 10,000-fold more potent than first generation compounds. Currently available RIAs for plasma estradiol lack sufficient sensitivity to measure levels during aromatase inhibition and, thus, to assess drug potency precisely. The availability of an ultrasensitive bioassay for estradiol provided the opportunity to accurately assess the potency of a new third generation triazole aromatase inhibitor, letrozole (CGS 20267). We used this assay to measure estradiol levels in 14 women with metastatic breast cancer given letrozole at doses of 100 micrograms to 5.0 mg/day over a 12-week period. The lack of differences between doses and sampling times allowed pooling of data. Basal estradiol levels of 7.2 +/- 1.9 pmol/L (mean +/- SEM, 1.95 +/- 0.52 pg/mL) fell to 0.26 +/- 0.11 pmol/L (0.07 +/- 0.03 pg/mL) during the first 6 weeks of therapy and to 0.48 +/- 0.18 pmol/L (0.13 +/- 0.05 pg/mL) during the second 6 weeks of therapy. Although plasma estradiol levels measured by RIA were significantly correlated with levels measured by bioassay (r = 0.79; P < 0.01), the degree of suppression assessed by the bioassay (95 +/- 2% after 6 weeks) was greater than that determined by the RIA (81 +/- 4%), presumably due to improved ability to measure very low estradiol levels. We conclude that plasma estradiol is suppressed by letrozole to lower levels than previously observed, with equivalent suppression at all doses studied. A slight, although not statistically significant, rebound in estradiol levels occurs during the second 6 weeks of therapy compared to the first 6 weeks. Maximum inhibition of aromatase is achieved at letrozole doses as low as 100 micrograms.
Aromatase Inhibitors↗
Organochlorine compounds in relation to breast cancer, endometrial cancer, and endometriosis: an assessment of the biological and epidemiological evidence.
There is an increasing public and scientific concern that certain chlorinated compounds, recognized as environmental pollutants, may cause estrogen-related neoplastic disease in humans. The main hypothesis has been that certain organochlorines, through their estrogenic actions, might cause breast cancer. From experimental studies, both in vitro and in vivo, there is evidence that certain organochlorine compounds may cause estrogenic effects, whereas others may cause antiestrogenic effects. In limited studies, some of these compounds in high doses have also been shown to increase and reduce the frequency of estrogen-related tumors in animals. The epidemiological findings regarding the association between organochlorines and breast cancer are inconclusive. However, the largest and best designed study has been interpreted as negative with respect to DDT and polychlorinated biphenyls (PCB) in relation to breast cancer. Associations between organochlorine exposure and endometrial cancer or endometriosis have even more limited empirical basis. The hypothesis that human exposure to environmental levels or organochlorines would favor an estrogenic overactivity leading to an increase in estrogen-dependent formation of mammary or endometrial tumors is not supported by the existing in vitro, animal and epidemiological evidence. It can, however, not be conclusively rejected on the basis of available data.
Animals↗
Using a pure muscle cross-leg flap.
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Humans↗
[The elderly and drug abuse].
LESA is a program of Lifestyle Enrichment for Senior Adults experiencing problems associated with their use of alcohol and other psychoactive drugs. It includes a direct service and a community education component. The treatment approach incorporates knowledge about the normal aging process, drug dependency, and holistic health, along with interventions from addiction treatment centres, holistic care, nursing and social work. The overall goal of the program is to improve the physical, psychosocial, spiritual, and environmental health of seniors who are living independently in the community and experiencing problems. To be admitted to this program, clients must be residents of Ottawa-Carleton who are 55 years of age or older; live independently; use psychoactive drugs in a manner presumed, or confirmed, to be hazardous; and express the desire for improved health or well-being. This article, based on documents available in both French and English, presents the special features of the program and its philosophy. Problematic drug use has four basic, interactive elements: the person(s) who uses the drug(s); the reasons for use; the drug(s) used; and the consequence of use. Effective intervention takes all of these elements into account. Early onset, intermittent problems, and late onset problem users, all have a reason for use. The positive and negative consequences of drug use, and the implications for seniors and for the rest of the population, are explained.
Aged↗
Enzyme- and sex-specific differences in the intralobular localizations and distributions of aryl sulfotransferase IV (tyrosine-ester sulfotransferase) and alcohol (hydroxysteroid) sulfotransferase a in rat liver.
Aryl sulfotransferase (AST) IV and alcohol (hydroxysteroid) sulfotransferase a (STa) catalyze the formation of sulfuric acid esters from a diverse array of xenobiotic and endogenous molecules in the liver. Despite the fact that many studies have addressed the metabolic importance and catalytic characteristics of these two sulfotransferases, relatively little is known about their comparative in situ localizations and intralobular distributions in liver. The present investigation utilized specific rabbit antisera prepared against AST IV and STa for immunoperoxidase staining of serial sections from livers of male and female Sprague-Dawley rats and computer-assisted image analysis of immunohistochemical staining intensity by means of microdensitometry. The overall concentration of AST IV was greater in males than in females, although the intralobular distribution of the enzyme was similar in the livers of both male and female rats, wherein centrilobular hepatocytes contained a greater level of AST IV than did midzonal cells, and midzonal hepatocytes had a greater concentration of AST IV than did periportal hepatocytes. In marked contrast, STa was present in livers of female rats at a much greater overall concentration than in livers of male rats. Furthermore, whereas the intralobular distribution of the enzyme was similar in both males and females, STa was present at greater concentrations in periportal hepatocytes than in midzonal hepatocytes and at greater concentrations in midzonal cells than in centrilobular hepatocytes. Significant intrazonal heterogeneity in STa levels within hepatocytes was also observed, particularly in livers of female rats. These results indicate that, whereas the overall hepatic concentrations of these enzymes are clearly sex-dependent, the intralobular distributions of AST IV and STa are characteristic of each particular sulfotransferase.
Amino Acid Sequence↗
Nutrients and gastric cancer risk. A population-based case-control study in Sweden.
A population-based case-control study of gastric cancer was conducted in areas with contrasting incidence rates in Sweden. Face-to-face interviews were carried out with 338 (74.1%) of all eligible cases and 679 (77.3%) of the selected controls. Consumption of selected nutrients during adolescence and 20 years prior to interview was estimated, together with life-time intake of vitamin supplements. Ascorbic acid and beta-carotene had an unequivocal protective effect, but alpha-tocopherol and nitrate were also negatively associated with gastric-cancer risk. In a multivariate analysis including all of these factors, only ascorbic acid remained a significant protective factor. The only macronutrient positively associated with the risk of gastric cancer was fat: intake 20 years prior to interview, but not during adolescence, was found to have a significant impact. Supplementation with vitamins almost halved the risk after adjustment for dietary intake of the corresponding vitamins. While the protective effect of vitamin C and beta-carotene could conceivably be ascribed to other agents in the diet, the strong negative association between supplementation with vitamin C and risk of gastric cancer supports the hypothesis of a protective role of this anti-oxidant.
Age Factors↗
Tobacco, alcohol and the risk of gastric cancer. A population-based case-control study in Sweden.
Previous studies have provided conflicting information on the role of tobacco and alcohol in gastric carcinogenesis. A population-based case-control study with 338 histologically confirmed gastric-cancer cases and 679 control subjects was conducted. Information relating to life-time tobacco consumption, alcohol intake and diet during adolescence and 20 years before interview, and to socio-economic conditions was obtained through face-to-face interviews. Current cigarette smokers were found to have a greater risk than non-users of tobacco. The duration of cigarette or pipe smoking was positively associated with gastric-cancer risk. There was significant interaction between tobacco use and fruit consumption. High fruit intake was more protective among users of tobacco than among non-users, and the risk estimates associated with cigarette smoking were higher among those with low fruit consumption than among frequent fruit-eaters. Likewise, though to a lesser extent, vegetable intake interacted with tobacco use. Snuff dipping and alcohol intake was not associated with gastric-cancer risk. However, high alcohol intake tended to increase the risk associated with tobacco use. This study adds further support to the role of tobacco smoking in gastric carcinogenesis, and demonstrates that high intake of fruits and vegetables may be particularly beneficial in smokers.
Adult↗
Early-life risk indicators of gastric cancer. A population-based case-control study in Sweden.
Exposures early in life seem to play an important role in the development of gastric cancer, but their nature is not well understood. In a population-based case-control study, we examined weight, height and body-mass index (BMI) at the age of 20 as well as indices of socioeconomic conditions. Face-to-face interviews were conducted with 338 of 456 eligible histologically confirmed gastric cancer patients and 679 of 880 eligible control subjects, sampled from population registers and frequency matched by age and gender. Gastric cancer risk was negatively associated with height. Risk was positively, associated with weight at age 20 in both sexes. The highest BMI-quartile was associated with an increased risk. This association between BMI and risk was confined to BMI at age 20, and disappeared for BMI 20 years prior to interview. High socioeconomic status (SES) as well as long education carried a decreased risk of gastric cancer. Number of siblings was positively associated with risk. Factors related to short stature and high adolescent body weight are associated with an increased risk of gastric cancer, as is a high number of siblings. These factors may reflect influences of dietary patterns early in life.
Adolescent↗
Risk factors for colorectal cancer in patients with ulcerative colitis: a case-control study.
BACKGROUND/AIMS: The risk of colorectal cancer increases in patients with ulcerative colitis, most markedly among young patients and/or those with extensive disease at onset. However, it is unknown whether individual risk can be predicted more precisely and whether cancer risk can be reduced by long-term treatment with sulfasalazine. METHODS: In a population-based cohort of 3112 patients with ulcerative colitis, we compared 102 cases of colorectal cancer and 196 matched controls without cancer. Hospital records were used to abstract information on pharmacological therapy, disease activity, and extraintestinal manifestations. The relative risk (RR) of cancer was estimated by conditional logistic regression. RESULTS: Pharmacological therapy, especially sulfasalazine, lasting at least 3 months was associated with a significant protective effect (RR, 0.38; 95% confidence interval [CI], 0.20-0.69) independent of disease activity. There was also a tendency to an independent protective effect for cigarette smoking (RR, 0.15; 95% CI, 0.02-1.25) and higher disease activity (RR, 0.80; 95% CI, 0.49-1.33). CONCLUSIONS: The risk of colorectal cancer among patients with ulcerative colitis can be reduced through pharmacological therapy. This finding is consistent with the reports of a protective effect of aspirin among individuals in the general population.
Adolescent↗
Estradiol inhibits growth hormone receptor gene expression in rabbit liver.
We studied the ontogeny of GH receptor mRNA levels and the effect of exogenous estradiol administration on GH receptor mRNA levels in rabbit liver. A solution hybridization-RNase protection assay revealed a predominant 370-base long protected band corresponding to the mRNA encoding the transmembrane GH receptor, and a 241-base long protected band, representing about 9.0%, with the predicted size for the truncated form of the GH receptor. To study the developmental profile of GH receptor expression, we studied 12 female rabbits, at ages 1, 3, 5 and 7 months. Maximal GH receptor mRNA levels were observed in 3-month-old animals and decreased in 7-month-old animals. To investigate the effect of estradiol, 8-week-old immature female rabbits were randomly divided into five groups, and received subcutaneous pellets containing either placebo or estradiol at doses of 0.1, 0.5, 1.5 and 5.0 mg for 3 weeks. Exogenous administration of estradiol, at doses that resulted in physiological circulating levels, induced a reduction in GH receptor expression, measured both by GH binding (36 and 46%), and GH receptor mRNA levels (38 and 87%), in animals receiving pellets containing 1.5 and 5.0 mg of estradiol, respectively. We conclude that estradiol decreases GH receptor expression in rabbit liver. The results of our study suggest that there is an inverse relationship between circulating estrogen concentrations and liver GH receptor expression.
Aging↗
Involvement of cytochrome P450 2E1-like isoform in the activation of N-nitrosobis(2-oxopropyl)amine in the rat nasal mucosa.
Induction of tumours in the nasal olfactory region of MRC rats by N-nitrosobis(2-oxopropyl)amine (BOP) is inhibited by orchiectomy and restored by testosterone. These results suggest the involvement of a sex-specific enzyme in BOP bioactivation in rat nasal mucosa. The present study was undertaken to identify this enzyme. Enzyme-linked immunosorbent assay (ELISA) and the metabolism of known substrates (p-nitrophenol) pointed to a microsomal cytochrome P450 (P450) 2E1-like isoform as a candidate enzyme. A correlation was found between the enzyme activity in nasal mucosal microsomes and serum testosterone levels. Four times more activity was detected in the nasal mucosa than in the liver of male rats. Vanillin inhibited the activity of the nasal mucosal enzyme to a greater extent than that of the liver enzyme. The overall results suggest that a nasal mucosal P450 2E1-like isoform is involved in BOP metabolism.
Animals↗
Insecticide-induced lupus erythematosus.
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Adult↗
Estrogen levels in childhood determined by an ultrasensitive recombinant cell bioassay.
We hypothesized that estradiol levels are higher in prepubertal girls than in prepubertal boys and that this greater secretion of estradiol might drive the more rapid epiphyseal development and earlier puberty in girls. Since previous estradiol assays have lacked adequate sensitivity to test the hypothesis of higher estradiol levels in girls, we developed a new ultrasensitive assay to measure estrogen levels. The assay uses a strain of Saccharomyces cerevisiae genetically engineered for extreme sensitivity to estrogen. Yeast were transformed with plasmids encoding the human estrogen receptor and an estrogen-responsive promoter fused to the structural gene for beta-galactosidase. Ether extracts of 0.8 ml of serum were incubated with yeast for 8 h and the beta-galactosidase response was used to determine estrogen bioactivity relative to estradiol standards prepared in charcoal-stripped plasma. The assay was highly specific for estradiol with < 3% cross-reactivity with estrone, estriol, or estradiol metabolites. The detection limit was < 0.02 pg/ml estradiol equivalents (100-fold lower than existing assays). Using this assay, we measured estrogen levels in 23 prepubertal boys (9.4 +/- 2.0 yr) and 21 prepubertal girls (7.7 +/- 1.9 [SD] yr). The estrogen level in girls, 0.6 +/- 0.6 pg/ml estradiol equivalents, was significantly greater than the level in boys, 0.08 +/- 0.2 pg/ml estradiol equivalents (P < 0.05). We conclude that the ultrasensitive recombinant cell bioassay for estrogen is approximately 100-fold more sensitive than previous estradiol assays, that estrogen levels are much lower prepubertally, in both sexes, than reported previously, and that prepubertal girls have 8-fold higher estrogen levels than prepubertal boys.
Adolescent↗