University of Tennessee Health Science Center

About: University of Tennessee Health Science Center is a education organization based out in Memphis, Tennessee, United States. It is known for research contribution in the topics: Population & Transplantation. The organization has 15716 authors who have published 26884 publications receiving 1176697 citations.

Is a fall just a fall: correlates of falling in healthy older persons. The Health, Aging and Body Composition Study.

Abstract: OBJECTIVES: To identify factors associated with falling in well-functioning older people. DESIGN: Cross-sectional analyses of report of falls over the past 12 months using baseline data from the Health, Aging and Body Composition Study. SETTING: Clinic examinations in Pittsburgh, Pennsylvania, or Memphis, Tennessee. PARTICIPANTS: Three thousand seventy-five high-functioning black and white elderly aged 70 to 79 living in the community. MEASUREMENTS: Physical function assessed using self-report and performance measures. Health status indicators included diseases, medication use, and body composition measures. RESULTS: Almost one-quarter (24.1%) of women and 18.3% of men reported at least one fall within the year before the baseline examination. Fallers were more likely to be female; white; report more chronic diseases and medications; and have lower leg strength, poorer balance, slower 400-meter walk time, and lower muscle mass. In men, multivariate logistic regression models showed white race (adjusted odds ratio (OR) = 1.4, 95% confidence interval (CI) = 1.2-1.6), slower 6-meter walk speed (OR = 1.1, 95% CI = 1.0-1.3), poor standing balance (OR = 1.2, 95% CI = 1.0-1.4), inability to do 5 chair stands (OR = 1.7, 95% CI = 1.3-1.9), report of urinary incontinence (UI) (OR = 1.5, 95% CI = 1.1-2.0), and mid-quintile of leg muscle strength (OR = 0.6, 95% CI = 0.4-0.9) to be independently associated with report of falling. In women, benzodiazepine use (OR = 1.6, 95% CI = 1.0-2.6), UI (OR = 1.5, 95% CI = 1.2-1.9), and reported difficulty in rising from a chair (OR = 1.4, 95% CI = 1.2-1.6) were associated with past falls. CONCLUSION: Falls history needs to be screened in healthier older adults. Even for well-functioning older persons, specific correlates of falling can be identified to define those at risk.

Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the Women's Health Initiative randomised placebo-controlled trial.

Abstract: Summary Background By contrast with many observational studies, women in the Women's Health Initiative (WHI) trial who were randomly allocated to receive oestrogen alone had a lower incidence of invasive breast cancer than did those who received placebo. We aimed to assess the influence of oestrogen use on longer term breast cancer incidence and mortality in extended follow-up of this cohort. Methods Between 1993 and 1998, the WHI enrolled 10 739 postmenopausal women from 40 US clinical centres into a randomised, double-masked, placebo-controlled trial. Women aged 50–79 years who had undergone hysterectomy and had expected 3-year survival and mammography clearance were randomly allocated by a computerised, permuted block algorithm, stratified by age group and centre, to receive oral conjugated equine oestrogen (0·625 mg per day; n=5310) or matched placebo (n=5429). The trial intervention was terminated early on Feb 29, 2004, because of an adverse effect on stroke. Follow-up continued until planned termination (March 31, 2005). Consent was sought for extended surveillance from the 9786 living participants in active follow-up, of whom 7645 agreed. Using data from this extended follow-up (to Aug 14, 2009), we assessed long-term effects of oestrogen use on invasive breast cancer incidence, tumour characteristics, and mortality. We used Cox regression models to estimate hazard ratios (HRs) in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00000611. Findings After a median follow-up of 11·8 years (IQR 9·1–12·9), the use of oestrogen for a median of 5·9 years (2·5–7·3) was associated with lower incidence of invasive breast cancer (151 cases, 0·27% per year) compared with placebo (199 cases, 0·35% per year; HR 0·77, 95% CI 0·62–0·95; p=0·02) with no difference (p=0·76) between intervention phase (0·79, 0·61–1·02) and post-intervention phase effects (0·75, 0·51–1·09). In subgroup analyses, we noted breast cancer risk reduction with oestrogen use was concentrated in women without benign breast disease (p=0·01) or a family history of breast cancer (p=0·02). In the oestrogen group, fewer women died from breast cancer (six deaths, 0·009% per year) compared with controls (16 deaths, 0·024% per year; HR 0·37, 95% CI 0·13–0·91; p=0·03). Fewer women in the oestrogen group died from any cause after a breast cancer diagnosis (30 deaths, 0·046% per year) than did controls (50 deaths, 0·076%; HR 0·62, 95% CI 0·39–0·97; p=0·04). Interpretation Our findings provide reassurance for women with hysterectomy seeking relief of climacteric symptoms in terms of the effects of oestrogen use for about 5 years on breast cancer incidence and mortality. However, our data do not support use of oestrogen for breast cancer risk reduction because any noted benefit probably does not apply to populations at increased risk of such cancer. Funding US National Heart, Lung, and Blood Institute; Wyeth.

Specific Inhibitors of p38 and Extracellular Signal-Regulated Kinase Mitogen-Activated Protein Kinase Pathways Block Inducible Nitric Oxide Synthase and Tumor Necrosis Factor Accumulation in Murine Macrophages Stimulated with Lipopolysaccharide and Interferon-γ

Abstract: Whether p38 and extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase cascades are required for inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF) accumulation in RAW 264.7 murine macrophages exposed to lipopolysaccharide (LPS) plus recombinant interferon-gamma (rIFN-gamma) was investigated. By use of Western blotting for iNOS detection and ELISA for quantitation of TNF secretion, three selective inhibitors of these pathways were tested (the p38 inhibitors SB202190 and SB203580 and the MEK 1,2/ERK inhibitor PD98059). Dose-related inhibition of iNOS production was demonstrated when inhibitors were added 1 h before, simultaneously with, or 1 h after LPS plus rIFN-gamma stimulation. In contrast, inhibition of TNF secretion was observed only when cells were preincubated with these agents. Thus, both the p38 and ERK pathways are involved in the up-regulation of iNOS and TNF production by murine macrophages, and specific inhibitors of these pathways block macrophage iNOS production even when added 1 h after activation of these cells.