DHEA-S levels and cardiovascular disease mortality in postmenopausal women: results from the National Institutes of Health--National Heart, Lung, and Blood Institute (NHLBI)-sponsored Women's Ischemia Syndrome Evaluation (WISE).

Context: Dehydroepiandrosterone sulfate (DHEA-S), a major circulating sex steroid prohormone, declines with age. Low levels have been associated with increased cardiovascular disease (CVD) risk and all-cause mortality, although these results have not been consistently replicated, particularly in women.

Objective: Our objective was to examine the association of circulating DHEA-S levels, CVD, and mortality risk among postmenopausal women with suspected myocardial ischemia.

Comprehensive evaluation of ESR2 variation and ovarian cancer risk.

Studies indicate that estrogen receptor beta, encoded by the ESR2 gene on chromosome 14q, may play a role in ovarian carcinogenesis. Using the genetic structure data generated by the Breast and Prostate Cohort Consortium (BPC3), we have comprehensively characterized the role of haplotype diversity in ESR2 and risk of ovarian cancer. Five haplotypes with a frequency of > or =5% were observed in White subjects and five haplotype tagging SNPs (htSNP) were selected to capture the locus diversity with a minimum R(h)(2) of 0.

Haplotypes of the estrogen receptor beta gene and breast cancer risk.

Exposure to exogenous (oral contraceptives, postmenopausal hormone therapy) and endogenous (number of ovulatory cycles, adiposity) steroid hormones is associated with breast cancer risk. Breast cancer risk associated with these exposures could hypothetically be modified by genes in the steroid hormone synthesis, metabolism and signaling pathways. Estrogen receptors are the first step along the path of signaling cell growth and development upon stimulation with estrogens.

Sequence variants of estrogen receptor beta and risk of prostate cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium.

Background: Estrogen receptor beta (ESR2) may play a role in modulating prostate carcinogenesis through the regulation of genes related to cell proliferation and apoptosis.

Methods: We conducted nested case-control studies in the Breast and Prostate Cancer Cohort Consortium (BPC3) that pooled 8,323 prostate cancer cases and 9,412 controls from seven cohorts. Whites were the predominant ethnic group.

Association between serum beta-carotene levels and decline of cognitive function in high-functioning older persons with or without apolipoprotein E 4 alleles: MacArthur studies of successful aging.

Background: Growing evidence from animal studies suggests an interaction between antioxidants and apolipoprotein E (APOE) alleles on cognitive functioning. We used data from a 7-year cohort study of high-functioning older persons to explore whether the associations between serum beta-carotene level and subsequent decline of cognitive function differed by APOE 4 genotype.

Methods: Baseline information on sociodemographic characteristics, serum beta-carotene level, inflammation markers, APOE genotype, and cognitive functioning measured by a 9-item Short Portable Mental Status Questionnaire (SPMSQ) was obtained in 455 survivors.

Education and APOE-e4 in longitudinal cognitive decline: MacArthur Studies of Successful Aging.

Longitudinal data from the MacArthur Study of Successful Aging were used to test for interactions between education and apolipoprotein E (APOE) genotype with respect to time trends in cognitive performance. Interactions between education, APOE-e4 status, and time were found for overall cognitive function, and for subscales measuring memory and naming: The presence of the e4 allele was associated with steeper declines in cognition for those with a greater than eighth-grade education. For those with an eighth-grade education or less, time trends did not differ by APOE genotype.

Genetic variation in angiotensin I-converting enzyme (ACE) and breast cancer risk: the multiethnic cohort.

The A-240T and I/D polymorphisms in the angiotensin I-converting enzyme (ACE) gene are markers of circulating ACE levels and have been associated with numerous cardiovascular disease outcomes. More recently, the low-activity A and I alleles at these polymorphic sites have been inversely related with breast cancer risk. We assessed the relationship between the A-240T and I/D ACE variants and breast cancer risk in a case-control analysis (n = 1263 cases with invasive breast cancer and 2269 controls) among African-American, Japanese, Latina, and white women in the Multiethnic Cohort Study.

Modeling and E-M estimation of haplotype-specific relative risks from genotype data for a case-control study of unrelated individuals.

The US National Cancer Institute has recently sponsored the formation of a Cohort Consortium (http://2002.cancer.gov/scpgenes.

The relationship between twenty missense ATM variants and breast cancer risk: the Multiethnic Cohort.

Deficiencies in tasks of detecting and repairing DNA damage lead to mutations and chromosomal abnormalities, a hallmark of cancer. The gene mutated in ataxia-telangiectasia (A-T), ATM, is a proximal component in performing such tasks. Studies of A-T families have suggested an increased risk of breast cancer among obligate female heterozygous carriers of ATM mutations.

The role of APOE-epsilon4 in longitudinal cognitive decline: MacArthur Studies of Successful Aging.

Background: While a genetic risk factor for late-onset AD, the effects of the epsilon4 allele of the APOE gene on cognitive functioning more generally remain unclear.

Objective: To assess the role of the epsilon4 allele of the APOE gene in longitudinal cognitive decline.

Methods: Multiple measures of cognitive function were assessed longitudinally in the MacArthur Successful Aging Study, a population-based cohort free of frank impairment at baseline.

Treatment of hypertension in African Americans and Latinos: the effect of JNC VI on urban prescribing practices.

In 1997, national recommendations for the treatment of hypertension were made in the form of the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). African American hypertensives are considered a special population with a higher prevalence of hypertension, and therefore, unique treatment needs. The study objective was to review medication use among an African American and Latino urban population in relation to the JNC recommendations.

Risk factors for human exposure to raccoon rabies during an epizootic in Connecticut.

The emergence of rabies among terrestrial wildlife poses increasing but poorly defined risks to people. In particular, events leading to human exposure to rabies virus via mammalian reservoirs remain elusive. Thus, we determined those risk factors associated with human exposure to rabies-positive animals during a raccoon rabies epizootic in Connecticut.

Manual measurement of QT dispersion in patients with acute myocardial infarction and nondiagnostic electrocardiograms.

Objective: To determine whether manually measured QT dispersion (QTD) may be a useful diagnostic adjunct for acute myocardial infarction (AMI) in emergency department patients with chest pain (CP) and nondiagnostic initial electrocardiograms (ECGs).

Methods: This was a retrospective review of a cohort of patients admitted to the coronary triage unit (CTU) at a large urban facility over a two-year period (1997-1999). Cases included all patients with nondiagnostic initial ECGs diagnosed as having AMI by enzymatic criteria.

Delayed presentation for care during acute myocardial infarction in a Hispanic population of Los Angeles County.

Background: Delay in seeking care for acute myocardial infarction (AMI) has been well described in some populations, but little research has been conducted on delay by minority groups, such as Latinos and Asians. This study sought to determine the degree of delay and mode of access of patients with AMI presenting to an inner-city hospital serving an ethnically diverse population.

Methods And Results: This study was a retrospective case series of Latino, Asian, African-American and Caucasian patients diagnosed in the emergency department (ED) with chest pain (CP) and AMI, during a 2-year period.

Risk factors for cardiovascular and cerebrovascular death among African Americans and Hispanics in Los Angeles, California.

Objective: To describe the risk factors associated with cardiovascular mortality in the African American (AA) and Hispanic populations in Los Angeles County in an effort to define causes for the excess mortality seen in AAs.

Methods: This was a longitudinal analysis of all-cause, cardiovascular, and cerebrovascular mortality in a large, prospective multiethnic cohort of individuals aged 45-74 years. Death rates between AA and Hispanic men and women during the six-year period from 1993 to 1998 due to hypertension, cardiomyopathy, acute myocardial infarction (AMI), ischemic heart disease, and stroke were compared.

A prospective study of the effect of fracture on measured physical performance: results from the MacArthur Study--MAC.

Objective: To examine the impact of fractures on measured physical performance and to assess whether specific fractures have unique sequelae.

Subjects: 762 men and women, aged 70 to 79 at baseline, who were part of the MacArthur Study of Successful Aging.

Design: A longitudinal case-cohort: those with prevalent fractures at baseline were excluded; cases were persons with a medically diagnosed hip, arm, spine, or wrist fracture during the follow-up period (1988-1995).

Evidence for an interaction between apolipoprotein E genotype, gender, and Alzheimer disease.

Carriers of the apolipoprotein E (APOE) epsilon4 allele show significantly higher risk of Alzheimer disease (AD). The aim of this present study was to test the hypothesis that a significant interaction exists between APOE genotype and gender on AD. Interactions of epsilon4 by gender, although indicated in the literature, require further verification.

Androgen metabolism and prostate cancer: establishing a model of genetic susceptibility.

The prostate is an androgen-regulated organ, which has led to longstanding interest in the role of androgens in prostate carcinogenesis. Although evidence of a hormonal etiology for prostate cancer is strong, it is almost entirely circumstantial. Much of the problem in proving a causal relationship relates to the continued difficulties in reliably measuring human tissue-specific exposure to endogenous steroid hormones.

Lifelong estrogen exposure and cognitive performance in elderly women.

Fluctuating endogenous and exogenous estrogens influence cognition in women. In this study, cognitive functioning in elderly women was examined by applying methodology used in understanding the effects of chronic estrogen exposure on hormone-sensitive tissue other than the brain. An index, combining menstrual, reproductive, and physical markers associated with estrogen levels, was developed for elderly, nondemented, predominantly Caucasian women (n = 87).

Emergence of raccoon rabies in Connecticut, 1991-1994: spatial and temporal characteristics of animal infection and human contact.

The North American raccoon rabies epizootic continues to expand, now affecting most of New England. In 1990, raccoons became the vertebrate most often reported rabid in the United States. Emergence of this zoonosis poses increasing, but poorly defined risks to humans.

Epidemiology of firearm mortality and injury estimates: state of Connecticut, 1988-1993.

Study Objectives: To retrospectively determine the 6-year cumulative incidence rate of firearm mortality and estimate nonfatal firearm injuries in Connecticut.

Methods: Retrospective analysis of data originating from the Connecticut State Medical Examiner's Office and records from the Trauma Registry of one urban hospital.

Results: From January 1988 through December 1993, 1,625 Connecticut residents died from firearm-related injuries.

Margin to craton expansion of late ordovician benthic marine invertebrates.

A biostratigraphic survey of 57 Late Ordovician marine shelly invertebrates from the Climacograptus manitoulinensis zone of eastern Canada supports suggestions that throughout the Early Phanerozoic benthic marine speciations occurred preferentially in marginal marine environments. The species subsequently spread onto the craton. There is no obvious positive correlation between the times of first appearance of new associations or novel communities along the continental margin and the first appearance on the craton of the species making up these communities.