Determinants of tissue estradiol levels and biologic responsiveness in breast tumors

Estradiol stimulates the growth of breast tumor cells in both pre- and post menopausal women. Following the menopause, the levels of estradiol in breast tumor tissues are similar to those from tumors obtained prior to cessation of ovarian function, even though plasma estrogen levels are 10–50 fold lower in post- than in premenopausal women. These observations suggested the possibility of enhanced estradiol uptake from plasma or in situ synthesis in post-menopausal women. We systematically studied these possibilities in a series of model systems. Initially we demonstrated a very high affinity estradiol binding site in tissues from castrated rats. Enhanced uptake occurred under conditions of low plasma estrogen levels when compared to animals with higher estradiol levels. In situ synthesis also occurred both through the sulfatase and aromatase pathways. In further studies, we compared uptake from plasma with in situ synthesis via aromatase in a nude mouse model. Under the conditions utilized, in situ synthesis resulted in much higher tissue estradiol levels and tumor growth rates than did uptake from plasma. During these studies we demonstrated that tumors deprived of estradiol developed mechanisms rendering them more sensitive to estrogen. This involved the ability of cells to adapt to estradiol deprivation to allow them to be responsive to four log lower amounts of estrogen than when studied under wild type conditions. In addition, cells adapted by increasing their level of aromatase and thus developing the capability to become more sensitive to estrogen precursors. Taken together, these studies demonstrate that breast cancer tissue is highly plastic and can adapt to conditions of estrogen deprivation via a variety of mechanisms.     

Smoking practices in New York City: The use of a population-based survey to guide policy-making and programming

To inform New York City’s (NYC’s) tobacco control program, we identified the neighborhoods with the highest smoking rates, estimated the burden of second-band smoke exposure, assessed the early response to state taxation, and examined cessation practices. We used a stratified random design to conduct a digit-dialed telephone survey in 2002 among 9,674 New York City adults. Our main outcome measures included prevalence of cigarette smoking, exposure to second-hand smoke, the response of smokers to state tax increases, and cessation practices. Even after controlling for sociodemographic factors (age, racelethnicity, income, education, marital status, employment status, and foreign-born status) smoking rates were highest in Central Harlem and in the South Bronx. Sixteen percent of nonsmokers reported frequent exposure to second-hand smoke at home or in a workplace. Among smokers with a child with asthma, only 33% reported having a no-smoking policy in their homes. More than one fifth of smokers reported reducing the number of cigarettes they smoked in response to the state tax increase. Of current smokers who tried to quit, 65% used no cessation aid. These data were used to inform New York City’s smoke-free legislation, taxation, public education, and a free nicotine patch give-away program. In conclusion, large, local surveys can provide essential data to effectively advocate for, plan, implement, and evaluate a comprehensive tobacco control program. Dr. Mostashari (the guarantor) made substantial contributions to the conception, design, and supervision of this paper, the analysis and interpretation of data, the drafting of the paper, critical revisions of the paper for important intellectual content, and the acquisition of data and funding for this research. Dr. Kerker made substantial contributions to the analysis and interpretation of data, the drafting of the paper and critical revisions of the paper for important intellectual content. Ms. Hajat made substantial contributions to the acquisition of data and critical revisions of the paper for important intellectual content. Dr. Miller made substantial contributions to the conception of this paper and critical revisions of the paper for important intellectual content. Dr. Frieden made substantial contributions to the conception, design, and supervision of this paper and critical revisions of the paper for important intellectual content.     

Male Rape,Some Notes on the Laboratory Investigation

The incidence of sexual assault continues to escalate, and it is under-reported. Recent literature discusses the medical, legal, and psychological management of the female sexual assault victim, but little has been written regarding appropriate management of male sexual assault. This article focuses on the laboratory investigation in male rape case.     

The Effects of the Going Places Program on Early Adolescent Substance Use and Antisocial Behavior

This study evaluated the effects of a school-based intervention on growth trajectories of smoking, drinking, and antisocial behavior among early adolescents. Seven middle schools were randomized to intervention or comparison conditions and students in two successive cohorts (n = 1484) provided five waves of data from sixth to ninth grade. The Going Places Program, included classroom curricula, parent education, and school environment components. Latent growth curve analyses demonstrated significant treatment group effects, including reducing increases in friends who smoke, outcome expectations for smoking, and smoking progression, but had non-significant effects on drinking or antisocial behavior. The Going Places Program was effective in preventing increases in smoking progression, but its efficacy as a more cross-cutting problem behavior preventive intervention was not confirmed.     

Analysis of Prior Health System Contacts as a Harbinger of Subsequent Fatal Injury in American Indians

CONTEXT: Many American Indian nations, tribes, and bands are at an elevated risk for premature death from unintentional injury. Previous research has documented a relationship between alcohol-related injury and subsequent injury death among predominately urban samples. The presence or nature of such a relationship has not been documented among American Indians living in the northern plains. PURPOSE: The purpose of this study was to identify and characterize any association between prior injury and/or alcohol use contacts with the Indian Health Service (IHS) and subsequent alcohol-related injury death that may suggest opportunities for mitigation. METHODS: Death certificates of American Indians who died from injury (ICD-9-E 800-999) in a rural IHS area over 6 consecutive years were linked to IHS acute-care facility records and toxicology reports. Deaths and prior IHS contacts were stratified by alcohol use as a contributing factor. Of the 526 injury deaths involving American Indians in the IHS area studied, 411 (78%) were successfully linked to IHS records. One hundred fifty-two of these cases met the inclusion criteria, with an additional 98 cases identified as a comparison group. FINDINGS: No differences in alcohol use at time of death between groups with and without prior health care contact (for injury or alcohol) could be determined (81% vs 73%). A significant relationship was found between previous visits for acute or chronic alcohol use and subsequent alcohol-related fatalities (P =.01). CONCLUSIONS: Based on these findings, injury-prevention activities in the population studied should be initiated at the time of any health-system contact in which alcohol use is identified. Intervention strategies should be developed that convey the immediate risk of death from injury in these patients.