PubMed · 4317963
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E B Chung. 1970. Multiple bile-duct hamartomas.. https://doi.org/10.1002/1097-0142(197008)26%3A2%3C287%3A%3Aaid-cncr2820260207%3E3.0.co%3B2-v
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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.
A paucity of substantive data from clinical drug trials is available specifically evaluating the effects of therapy for hypercholesterolemia in African-Americans, even though a substantial number are candidates for medical advice and intervention for high blood cholesterol. The efficacy and safety of lovastatin in 459 African-Americans with hypercholesterolemia were studied in the Expanded Clinical Evaluation of Lovastatin study, a multicenter, double-blind, diet- and placebo-controlled trial. This trial involved 8,245 patients who were randomly assigned, regardless of race, to receive placebo or lovastatin at doses of 20 mg once daily, 40 mg once daily, 20 mg twice daily, or 40 mg twice daily for 48 weeks. Among African-Americans, lovastatin produced sustained, dose-related (p <0.001) decreases in low-density lipoprotein cholesterol (20% to 38%), total cholesterol (14% to 28%), and triglycerides (8% to 15%). From 75% to 96% of African-Americans treated with lovastatin achieved the National Cholesterol Education Program goal of low-density lipoprotien cholesterol <160 mg/di, and from 33% to 71% achieved the goal <130 mg/di. The safety profile of lovastotin in African-Americans was generally favorable. A relatively high incidence of creatine kinase levels greater than the upper limit of normal was observed in African-Americans during the study, i.e., 63% in the placebo group and similar levels in lovastatin treatment groups. Lovastatin is highly effective and generally well tolerated as therapy for primary hypercholesterolemia in African-Americans.
BACKGROUND: Black women with breast cancer have a decreased 5-year survival rate in comparison with white women, possibly because of less frequent use of mammography. Having a regular provider or source of health care is the most important determinant of mammography use. OBJECTIVE: To examine whether the difference in mammography use between elderly black women and elderly white women is related to the number of visits made to a primary care physician. DESIGN: Retrospective review of 1990 Health Care Financing Administration billing files (Medicare part B) from 10 states. SETTING: Outpatient mammography services in 10 states. PARTICIPANTS: Black women and white women, 65 years of age and older, residing in one of the 10 states. MEASUREMENTS: Any mammogram. Predictors included race, number of visits to a primary care physician (0, 1, 2, or 3 or more), median income of ZIP code of residence (a surrogate measure of income), and state. RESULTS: The following are findings from Georgia; similar results were found in each state studied. The mean age of the 335,680 women was 75 years; 20% were black. Sixty-eight percent of the black women and 69% of the white women made at least one visit to a primary care physician. Overall, 14% of the women had had mammography; black women had mammography less often than white women (9% compared with 15%). At each primary care visit level (1, 2, or 3 or more visits), black women had mammography less often than white women (1 visit, 7% compared with 15%; 2 visits, 12% compared with 21%; and 3 or more visits, 12% compared with 20%). Even among women who had made at least one visit to a primary care physician, a deficit for blacks occurred in each income quintile (lowest quintile, 13% compared with 20%; low, 10% compared with 18%; middle, 12% compared with 18%; high, 10% compared with 19%; and highest, 12% compared with 22%) and in each state (in Georgia, for example, the percentages were 14% compared with 21%). An age-, income-, and state-adjusted logistic model predicting mammography use for 2.9 million white women in all 10 states shows the powerful effect of primary care use on mammography (odds ratios for 1, 2, and 3 or more visits were, respectively, 2.73 [95% CI, 2.70 to 2.77]; 3.98 [CI, 3.93 to 4.03]; and 4.62 [CI, 4.58 to 4.67]). The same model fit to 250 000 black women shows a lesser effect (analogous odds ratios were 1.77 [CI, 1.67 to 1.87]; 2.49 [CI, 2.36 to 2.63]; and 3.15 [CI, 3.04 to 3.25]). CONCLUSION: Among older women, mammography is used less often for blacks than for whites. More frequent use of mammography is associated with more visits to a primary care physician in both groups, but the deficit for black women persists at each income level and in each state, even after primary care use is considered. Primary care visits are less likely to "boost" mammography use for black women than for white women.