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.     

Safety Behaviors of Abused Women After an Intervention During Pregnancy

Objective: To evaluate an intervention protocol, administered during pregnancy, for increasing safety-seeking behaviors of abused women.
Design: Prospective, ethnically stratified cohort analysis.
Setting: Public prenatal clinics.
Participants: Pregnant women reporting physical or sexual abuse in the year before or during the present pregnancy. One hundred thirty-two women met study criteria, received the intervention, and were followed for 1 year after the completion of the pregnancy.
Intervention: Three education, advocacy, and community referral sessions that included information on safety behaviors.
Main outcome Measure: Adoption of safety behaviors by abused women. Safety behaviors were measured before the intervention, twice during pregnancy, and at 2, 6, and 12 months after completion of the pregnancy.
Results: Repeated measures analysis of variance showed a significant increase in adoption of each safety behavior (p < .0001), with most behaviors showing a significant increase after the first intervention session.
Conclusions: Pregnant women who were abused and were offered an intervention protocol report a significant increase in safety behavior adoption during and after pregnancy. Abuse during pregnancy is common. Identification of abuse and immediate clinical intervention that includes information about safety behaviors can result in safety behavior adoption that may prevent future abuse and increase the safety and well-being of women and infants.     

Patterns and predictors of inpatient falls and fall-related injuries in a large academic hospital.

OBJECTIVES: Most research on hospital falls has focused on predictors of falling, whereas less is known about predictors of serious fall-related injury. Our objectives were to characterize inpatients who fall and to determine predictors of serious fall-related injury. METHODS: We performed a retrospective observational study of 1,082 patients who fell (1,235 falls) during January 2001 to June 2002 at an urban academic hospital. Multivariate analysis of potential risk factors for serious fall-related injury (vs no or minor injury) included in the hospital's adverse event reporting database was conducted with logistic regression to calculate adjusted odds ratios (aORs) with 95% confidence intervals (CI95) RESULTS: The median age of patients who fell was 62 years (interquartile range, 49-77 years), 50% were women, and 20% were confused. The hospital fall rate was 3.1 falls per 1,000 patient-days, which varied by service from 0.86 (women and infants) to 6.36 (oncology). Some (6.1%) of the falls resulted in serious injury, ranging by service from 3.1% (women and infants) to 10.9% (psychiatry). The most common serious fall-related injuries were bleeding or laceration (53.6%), fracture or dislocation (15.9%), and hematoma or contusion (13%). Patients 75 years or older (aOR, 3.2; CI95, 1.3-8.1) and those on the geriatric psychiatry floor (aOR, 2.8; CI95, 1.3-6.0) were more likely to sustain serious fall-related injuries. CONCLUSIONS: There is considerable variation in fall rates and fall-related injury percentages by service. More detailed studies should be conducted by floor or service to identify predictors of serious fall-related injury so that targeted interventions can be developed to reduce them.     

Posttraumatic Stress Symptoms and Distress Among Parents of Children With Cancer

In this study, we compared levels of posttraumatic stress symptoms (PTSS) and general psychological distress between parents of childhood cancer survivors and parents of children with Type 1 diabetes mellitus (DM1). In this study, we also examined potential risk factors for PTSS. Participants included 47 parents of childhood cancer survivors and 31 parents of children with DM1. Participants completed self-report measures of posttraumatic stress, general psychological distress, coping strategies, social network size, and perceived illness uncertainty. Findings revealed that parents of children surviving cancer reported higher levels of PTSS and general distress than parents of children with DM1. In the total sample, lower levels of emotion-focused coping and greater perceived uncertainty were associated with increased frequency of both PTSS and general psychological distress after we accounted for demographic and illness variables. Having a child with cancer may increase the risk for experiencing PTSS. Interventions are warranted that focus specifically on the reduction of PTSS in parents of children surviving cancer.     

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.