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PubMed · 13420610

[Black pigmentation].

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A B LERNER. 1956. [Black pigmentation].. https://pubmed.ncbi.nlm.nih.gov/13420610/

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Common charge-shift mutation Glu65Lys in K+ channel β₁-Subunit KCNMB1: pleiotropic consequences for glomerular filtration rate and progressive renal disease.

BACKGROUND: Glomerular filtration rate (GFR) is a heritable trait, and hyperfiltration (GFR increment in remnant nephrons) may accelerate renal functional decline in chronic kidney disease (CKD). Mesangial and vascular smooth myocytes control GFR by contraction, dependent on voltage-gated Ca(2+) influx, which is controlled by the regulatory β₁-subunit (KCNMB1) of large-conductance heteromeric K+ ('BK') channels. KCNMB1 gain-of-function variant Glu65Lys results in generalized vasorelaxation and thus protection against systemic hypertension. Here we asked whether the Glu65Lys variant influences GFR, in the basal state or during progressive renal decline. METHODS: We explored Glu65Lys effects on GFR in three populations spanning two ethnicities and two diseases (hypertension and nephrosclerosis). GFR was either estimated (eGFR from serum creatinine) or directly measured (iothalamate clearance). RESULTS: The 65Lys variant was relatively common, occurring on ∼5-10% of chromosomes in different biogeographic ancestry groups, and 65Lys carriers exhibited higher eGFR in two primary care populations: extreme BP values in Kaiser clinics (p = 0.029, accounting for ∼0.2% of trait variance), or treated hypertensives in VA clinics (p = 0.017, accounting for ∼0.9% of trait variance). In blacks with progressive renal disease (NIDDK AASK), 65Lys carriers displayed a steeper slope in GFR chronic decline (p = 0.030, accounting for ∼0.4% of trait variance), and Glu65Lys genotype also predicted time of onset of renal failure (log rank p = 0.019). CONCLUSIONS: Common KCNMB1 gain-of-function variant Glu65Lys influences GFR, and 65Lys carriers exhibit not only elevated baseline GFR, but also more rapid GFR decline (and consequent development of renal failure) in CKD. The results suggest that profiling patients at Glu65Lys can assist in gauging renal prognosis as well as selection of rational therapy in hypertension with progressive renal disease.

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A retrospective case-control study of the use of hormone-related supplements and association with breast cancer.

Hormone-related supplements (HRS), many of which contain phytoestrogens, are widely used to manage menopausal symptoms, yet their relationship with breast cancer risk has generally not been evaluated. We evaluated whether use of HRS was associated with breast cancer risk, using a population-based case-control study in 3 counties of the Philadelphia metropolitan area consisting of 949 breast cancer cases and 1,524 controls. Use of HRS varied significantly by race, with African American women being more likely than European American women to use any herbal preparation (19.2% vs. 14.7%, p=0.003) as well as specific preparations including black cohosh (5.4% vs. 2.0%, p=0.003), ginseng (12.5% vs. 7.9%, p<0.001) and red clover (4.7% vs. 0.6%, p<0.001). Use of black cohosh had a significant breast cancer protective effect (adjusted odds ratio 0.39, 95% CI: 0.22-0.70). This association was similar among women who reported use of either black cohosh or Remifemin (an herbal preparation derived from black cohosh; adjusted odds ratio 0.47, 95% CI: 0.27-0.82). The literature reports that black cohosh may be effective in treating menopausal symptoms, and has antiestrogenic, antiproliferative and antioxidant properties. Additional confirmatory studies are required to determine whether black cohosh could be used to prevent breast cancer.

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Factors affecting outcomes after radical cystectomy in African Americans.

BACKGROUND: Previous studies indicate that African Americans with bladder cancer have a worse outcome than Caucasians. Delay in seeking care and higher stage at presentation have been cited as possible reasons for the observed differences. The authors hypothesized that differences in hospital volume where patients undergo radical cystectomy may be responsible for race-based differences in outcomes after the procedure. METHODS: The authors analyzed data from the Health Care Cost and Utilization Project and identified 4862 patients who had undergone radical cystectomy between 1998 and 2002. In-hospital mortality, complications, and length of stay (LOS) in hospital were compared between patients grouped by race. Hospitals were categorized into tertiles by the average number of radical cystectomies performed per year (1-4 radical cystectomies, 5-10 radical cystectomies, and >10 radical cystectomies). Univariate and multivariate analyses were performed to determine predictors of mortality, complications, LOS, and the likelihood that patients would undergo cystectomy at a high/medium-volume hospital. RESULTS: African Americans had the highest in-patient mortality, complications, and LOS after radical cystectomy. They also were the least likely to undergo radical cystectomy at a high/medium-volume hospital. When the analyses were controlled for potential confounding factors, there was no difference in in-hospital mortality by race, but differences persisted in the other 3 outcome variables. African Americans had higher odds of complications (odds ratio [OR], 1.57; P = .001), longer LOS (25%; P = .001), and lower odds of undergoing cystectomy at a high/medium-volume hospital (OR, 0.74; P = .03) compared with Caucasians. CONCLUSIONS: Race was an important factor in determining outcomes after radical cystectomy for bladder cancer. African Americans were less likely to undergo cystectomy at a high-volume hospital, thereby placing them at a higher risk of postoperative complications which ultimately may affect their survival.

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