Treatment of hypertension and its effect on cardiovascular risk factors: data from the Framingham Heart Study

Analysis of the Framingham Heart Study experience between 1958 and 1970 showed a progressive increase in the rate of treatment and control of hypertension. With cross-sectional criteria to define diastolic hypertension, the treatment rate rose from 35% in 1958 through 1960 to 69% in 1968 through 1970 (p less than .001), and the treatment rate for sustained hypertension rose from 55% in 1958 through 1960 to 85% in 1968 through 1970 (p less than .001). Treated hypertensive subjects had higher pretreatment values of blood pressure but not of other cardiovascular risk factors than untreated hypertensive subjects. Treatment was more successful in controlling hypertension in later years (p less than .001), but in all years treatment reduced systolic and diastolic blood pressure without causing significant changes in mean serum cholesterol or glucose levels. In treated hypertensive subjects, the 8 year predicted risk of coronary heart disease declined by 2.3 events per 100 people compared with that in untreated hypertensive subjects (p less than .0001). The observed incidence of coronary heart disease was consistent with these predictions and suggested that treatment may be especially beneficial in subjects who have systolic blood pressures of 180 mm Hg or higher and who are treated for more than 2 successive years.     

Evidence linking glycated albumin to altered glomerular nephrin and VEGF expression, proteinuria, and diabetic nephropathy

BACKGROUND: Albumin modified by Amadori-glucose adducts has been linked to the development of diabetic nephropathy through its ability, independent of hyperglycemia, to activate protein kinase C-beta (PKC-beta), up-regulate the transforming growth factor-beta (TGF-beta) system, and stimulate expression of extracellular matrix proteins in glomerular cells, and by the demonstration that reducing the burden of glycated albumin ameliorates renal structural and functional abnormalities in the db/db mouse. METHODS: To probe whether the salutary effects consequent to lowering glycated albumin, which include reduction of albuminuria, relate to an influence of the Amadori-modified protein on nephrin, the podocyte protein critical to regulation of protein excretion, and on the angiogenic vascular endothelial growth factor (VEGF), which induces microvascular permeability, diabetic db/db mice were treated with a small molecule that inhibits the nonenzymatic glycation of albumin. RESULTS: Compared to nondiabetic db/m mice, diabetic controls exhibited increased urinary excretion of albumin and type IV collagen, elevated renal TGF-beta1 protein levels, reduced glomerular nephrin immunofluorescence and nephrin protein by immunoblotting, and increased glomerular VEGF immunostaining and renal VEGF protein content. Diabetic animals receiving test compound showed significant lowering of proteinuria, normalization of renal TGF-beta1 protein, and significant restoration of altered glomerular nephrin and VEGF expression. CONCLUSION: The findings causally implicate the increased glycated albumin associated with the diabetic state in the abnormal renal nephrin and VEGF expression found in diabetes, thereby promoting proteinuria and glomerulosclerosis.     

Race/ethnicity, poverty status, and renal transplant outcomes

BACKGROUND: There are known racial disparities in renal graft survival. Data are lacking comparing associations of race/ethnicity and socioeconomic status with graft failure and functional status after transplantation. Our goal was to test if African-American and Hispanic race/ethnicity and poverty are associated with worse outcomes following renal transplantation. METHODS: We performed a retrospective cohort study using a nationwide registry (United Network for Organ Sharing). We studied 4,471 adults who received renal transplants in 1990. Outcomes were graft failure and functional status over 10 years. RESULTS: Cumulative incidence of graft failure was higher among African-Americans and Hispanics than whites (77% vs. 64% vs. 60 %; P<0.001) and among transplant recipients living in the poorest areas (70% vs. 58% in the richest; P<0.001). African-American and Hispanic race/ethnicity were independently predictive of graft failure (RR 1.8, 95% CI 1.6-1.9; RR 1.3, 95% CI 1.2-1.6, respectively) in multivariate analyses but poverty status was not (RR 1.0, 95% CI 0.9-1.1). Days with impaired functional status were higher for African-Americans compared to whites (RR 1.6, 95% CI 1.3-1.9) but not independent of poverty. Poverty was independently associated with impaired functional status (RR 1.3, 95% CI 1.0-1.6). CONCLUSIONS: African-Americans and Hispanics had higher rates of graft failure compared to whites after adjustment for poverty and other covariates whereas poverty, but not race/ethnicity, was related to functional status following renal transplantation. National datasets should include individual-level measures of socioeconomic status in order to improve evaluation of social and environmental causes of disparities in renal transplant outcomes.     

The occurrence of hypothyroidism following radioactive iodine treatment of toxic nodular goiter is related to the TSH level

Background  Strategies to increase frequency of euthyroidism following radioactive (RAI) treatment of hyperthyroidism are required. Aims  To examine the role of TSH in development of hypothyroidism post RAI treatment in patients with Graves’ disease (N = 98) or toxic nodular goiter, TNG (N = 88). Design  This retrospective study examined thyroid status over a mean of 3.7 years post-RAI. Results  Although RAI dose was significantly higher in TNG group, hypothyroidism occurred more frequently in Graves’ disease (71.4 and 22.7%) P < 0.001. The TSH levels at the time of RAI treatment were lower in TNG patients who remained euthyroid, (0.4±0.1 vs. 1.2±0.5 mU/l, P < 0.0022). Conclusions  A higher frequency of euthyroidism occurs in patients with TNG than with Graves’ disease following RAI, particularly when suppressed TSH levels were suppressed at time of RAI-treatment.     

X-linked chronic granulomatous disease: correction of NADPH oxidase defect by retrovirus-mediated expression of gp91-phox

Chronic granulomatous disease (CGD) is an inherited immunodeficiency resulting from the inability of an individual's phagocytes to produce superoxide anions because of defective NADPH oxidase. The disease may be treated by bone marrow transplantation and as such is a candidate for somatic gene therapy. Two thirds of patients have defects in an X- linked gene (X-CGD) encoding gp91-phox, the large subunit of the membrane cytochrome b-245 component of NADPH oxidase. Epstein-Barr virus-transformed B-cell lines from patients with CGD provide a model system for the disease. We have used retrovirus-mediated expression of gp91-phox to reconstitute functionally NADPH oxidase activity in B-cell lines from three unrelated patients with X-CGD. The protein is glycosylated and membrane associated, and the reconstituted oxidase is appropriately activated via protein kinase C. The kinetics of superoxide production by such reconstituted cells is similar to that of normal B-cell lines. These data show the potential of gene therapy for this disease.     

A Randomized Trial to Compare Alternative Educational Interventions to Increase Colorectal Cancer Screening in a Hard-to-Reach Urban Minority Population with Health Insurance

This randomized controlled trial assessed different educational approaches for increasing colorectal cancer screening uptake in a sample of primarily non-US born urban minority individuals, over aged 50, with health insurance, and out of compliance with screening guidelines. In one group, participants were mailed printed educational material (n = 180); in a second, participants’ primary care physicians received academic detailing to improve screening referral and follow-up practices (n = 185); in a third, physicians received academic detailing and participants received tailored telephone education (n = 199). Overall, 21.5 % of participants (n = 121) received appropriate screening within one year of randomization. There were no statistically significant pairwise differences between groups in screening rate. Among those 60 years of age or older, however, the detailing plus telephone education group had a higher screening rate than the print group (27.3 vs. 7.7 %, p = .02). Different kinds of interventions will be required to increase colorectal cancer screening among the increasingly small population segment that remains unscreened. ClinicalTrials.gov Identifier: NCT02392143.     

T cell subsets and cellular immunity in end-stage renal disease

The T lymphocyte population was studied by immunofluorescent staining with monoclonal antibodies and laser flow cytometry in the blood of 50 patients with end-stage renal disease undergoing long-term maintenance intermittent hemodialysis. The absolute number of T cells was lower in patients receiving dialysis for more than one year (p less than 0.001), as was the absolute count of helper T cells (p less than 0.005). In patients under 30 years of age, the absolute number of helper T cells was markedly reduced, whereas the number of suppressor/cytotoxic T lymphocytes was not changed. In patients between the ages of 30 and 60 years, both helper and suppressor cells were significantly reduced. In patients over 60 years of age, only the number of helper T cells was reduced. The in vitro response of patients' lymphocytes was reduced both in the mixed lymphocyte reaction (p less than 0.01) and after phytohemagglutinin stimulation (p less than 0.001). Natural killer cytotoxicity of patients' peripheral blood mononuclear cells, however, was unaffected.