Placental biomarkers of phthalate effects on mRNA transcription: application in epidemiologic research

Background  

CYP19 and PPARγ are two genes expressed in the placental trophoblast that are important to placental function and are disrupted by phthalate exposure in other cell types. Measurement of the mRNA of these two genes in human placental tissue by quantitative real-time polymerase chain reaction (qPCR) offers a source of potential biomarkers for use in epidemiologic research. We report on methodologic challenges to be considered in study design.     

Recombinant human anti-transforming growth factor beta1 antibody therapy in systemic sclerosis: a multicenter, randomized, placebo-controlled phase I/II trial of CAT-192

OBJECTIVE: To evaluate CAT-192, a recombinant human antibody that neutralizes transforming growth factor beta1 (TGFbeta1), in the treatment of early-stage diffuse cutaneous systemic sclerosis (dcSSc). METHODS: Patients with SSc duration of <18 months were randomly assigned to the placebo group or to 1 of 3 CAT-192 treatment groups: 10 mg/kg, 5 mg/kg, 0.5 mg/kg. Infusions were given on day 0 and weeks 6, 12, and 18. The primary objective of this study was to evaluate the safety, tolerability, and pharmacokinetics of CAT-192. Secondary outcomes included the modified Rodnan skin thickness score (MRSS), the Scleroderma Health Assessment Questionnaire, assessment of organ-based disease, serum levels of soluble interleukin-2 receptor, collagen propeptides (N propeptide of type I [PINP] and type III collagen), and tissue levels of messenger RNA for procollagens I and III and for TGFbeta1 and TGFbeta2. RESULTS: Forty-five patients were enrolled. There was significant morbidity and mortality, including 1 death in the group receiving 0.5 mg/kg of CAT-192 and 3 deaths in the group receiving 5 mg/kg of CAT-192. There were more adverse events and more serious adverse events in patients receiving CAT-192 than in those receiving placebo, although these events were not more frequent in the high-dose treatment group. The MRSS improved in all groups during the study, but there was no evidence of a treatment effect for CAT-192. Improvement in the MRSS correlated with the disease duration (r = -0.54, P = 0.0008). Changes in the PINP level from baseline correlated with changes in the MRSS (r = 0.37, P = 0.027). CONCLUSION: We report the first evaluation of a systemically administered and repeatedly dosed anti-TGFbeta1 drug. In this pilot study, CAT-192, in doses up to 10 mg/kg, showed no evidence of efficacy. The utility of clinical and biochemical outcome measures and the feasibility of multicenter trials of early dcSSc were confirmed.     

Oral, injected and implanted contraceptives and breast cancer risk among U.S. Hispanic and non-Hispanic white women

Associations between oral contraceptive (OC) use and breast cancer have been reported, but few studies have considered associations in racial and ethnic minorities. Data regarding injected or implanted hormonal contraceptives are limited. In a case-control study of Hispanic (796 cases, 919 controls) and non-Hispanic white (1,522 cases, 1,596 controls) women in the U.S. southwest interviewed in 2000-2005, 49% of Hispanic controls and 66% of non-Hispanic white controls reported having used OC. Breast cancer odds ratios (OR) associated with OC use within the past 5 years were 1.22 (95% confidence interval (CI) 0.80, 1.84) among Hispanics, 1.28 (95% CI 0.93, 1.76) among non-Hispanic whites, 1.27 (95% CI 0.99, 1.63) for both ethnic groups combined and 1.53 (95% CI 0.98, 2.40) for estrogen receptor (ER) negative tumors. OC use for 20 years or longer was associated with ORs of 1.50 (95% CI 1.04, 2.17) for both ethnic groups combined, and 2.23 (95% CI 1.17, 4.25) for ER negative tumors. Hormonal contraceptive injections were used by 3.3% of Hispanic controls and 2.8% of non-Hispanic white controls, OR 1.23 (95% CI 0.88, 1.73). Fifteen cases and 2 controls reported use of a subdermal contraceptive implant, OR 8.59 (95% CI 1.92, 38.39). Associations between OC use and breast cancer in Hispanics are consistent with modestly increased risk among recent users and for ER negative tumors, as observed in other populations. Based on a small number of users of contraceptive implants, a significantly increased breast cancer risk was observed; continued surveillance of implant users may be warranted.     

Vacuum-assisted closure for radiation-associated wound complications

BACKGROUND AND OBJECTIVES: Vacuum-assisted closure (VAC) technology has proven to be effective in the management of soft tissue loss from infections, vascular insufficiency, and traumatic disorders and may have a similar benefit in the musculoskeletal oncology patient. This study reports a single institution's experience with VAC technology in the management of radiation-associated wound complications in patients with soft tissue sarcomas. MATERIALS: Twenty-two patients treated with both surgical intervention and radiation therapy developed either superficial or deep wound complications that were managed with the VAC device. This study group was compared to a retrospectively identified comparison group of 19 patients, in which the VAC device was not used. RESULTS: Hospital stay (P < 0.025), length of overall treatment (P < 0.025), number of operative debridements (P < 0.05) and success of wound closure without the need for soft tissue transposition (P < 0.01) was found to be significantly less in the study groups as compared to those not treated with the VAC device. CONCLUSION: VAC technology appears to be safe and effective in the treatment of radiation-associated wound complications.     

Body size,weight change,fat distribution and breast cancer risk in Hispanic and non-Hispanic white women

INTRODUCTION: The incidence of breast cancer varies among women living in the Southwestern part of the US. We evaluate how body size influences breast cancer risk among these women. METHODS: Cases (n = 2,325) diagnosed with breast cancer between October 1, 1999 and May 2004 residing in Arizona, Colorado, New Mexico, or Utah were matched to controls (n = 2,525). Participants were interviewed; height, weight, waist, and hip circumference were measured at the time of interview; blood was drawn. RESULTS: A large body mass index (BMI) at age 15 was inversely associated with pre-menopausal breast cancer risk in both non-Hispanic white (NHW) and Hispanic women (Odds ratio, ORs 0.68 95% CI 0.44, 1.04, and 0.65 95% CI 0.39, 1.08, respectively); BMI at age 15 also had an impact on subsequent breast cancer associated with obesity after menopause. Among post-menopausal women, recent exposure to hormones was an important modifier of risk associated with body size. Among women not recently exposed to hormones risk associated with obesity was 1.61 (95% CI 1.05, 2.45) for NHW women; gaining > or = 25 kg between 15 and age 50 was inversely associated with breast cancer among Hispanic women (OR 0.51, 95% CI 0.23, 1.14). A large weight gain and a large waist-to-hip ratio (WHR) was associated with an increased odds of having an estrogen receptor negative tumor among NHW only (OR 1.81, 95% CI 1.07, 3.08, and 2.04 95% CI 1.20,3.50). CONCLUSIONS: These findings suggest that the metabolic consequences of obesity on breast cancer risk differ between NHW and Hispanic women living in the Southwest.     

UNDERUTILIZATION OF MENTAL HEALTH SERVICES BY ASIANAMERICANS RESIDING IN THE UNITED STATES

Asian-Americans are the fastest-growing minority in the United States, and they are a culturally diverse group. Knowledge about this growing minority population is important for the purposes of planning appropriate mental health care. Asian-Americans living in the United States rarely use mental health services. The reasons for this, along with suggestions for developing more culturally sensitive mental health services, are presented. A model for cultural competence can provide a framework for psychiatric nurses and other mental health professionals (MHPs) to become more aware of Asian-American values and beliefs and provide more culturally sensitive care. Awareness tools are included to guide MHPs in determining whether culturally competent care is available locally to meet the needs of this underserved population.