Acute idiopathic tubulointerstitial nephritis: report of two cases and review of the literature

Two patients who presented with severe renal failure and evidence of generalized proximal tubular dysfunction were found to have severe diffuse acute tubulointerstitial nephritis on renal biopsy. No etiology could be found in either case. Both patients had dramatic improvement in renal function following steroid therapy. In the first reported case of its kind, one patient relapsed when steroids were withdrawn, but improved again with reinstitution of steroid therapy. These cases, as well as others in the literature, show that steroids are effective and may be necessary to improve renal function in some patients with acute idiopathic tubulointerstitial nephritis. Evidence of proximal tubular dysfunction is a clue to the presence of this disorder.     

Coexpression of hepatocyte growth factor and receptor (Met) in human breast carcinoma.

Expression of hepatocyte growth factor (HGF) and HGF receptor (HGFR, product of the met proto-oncogene) mRNA were examined by nonisotopic in situ hybridization in a spectrum of benign and malignant human breast tissues. mRNA for both HGFR and HGF was detected in benign ductal epithelium. Epithelial expression of HGF mRNA was particularly intense in regions of ductal epithelial hyperplasia. Positive expression of HGF (but not HGFR) mRNA was also found in adipocytes, endothelial cells, and to varying degrees in stromal fibroblasts. In 12 of 12 cases of ductal carcinoma in situ and infiltrating ductal carcinoma, carcinoma cells showed a heterogeneous pattern of expression for both HGFR and HGF mRNA. In infiltrating ductal carcinomas, intense expression of HGFR mRNA was not restricted to ductular structures but as also seen in non-duct-forming carcinoma cells. The same zones of the tumors (most commonly at the advancing margins) that expressed strongly HGFR mRNA often were also strongly positive for HGF mRNA, suggesting a possible autocrine effect. The expression pattern of HGFR protein in 25 cases including the same series of tissues used for in situ hybridization analysis was similar to that of HGFR mRNA, as determined by an immunoperoxidase technique. The finding that HGFR is expressed by both benign and malignant epithelium, and its not restricted to duct-forming structures, suggests that, although the potential for HGF/HGFR binding is maintained in malignancy, the response to ligand binding at the level of the receptor or the cellular response to receptor activation may change at some point during progression.     

Working conditions and health behavior as causes of educational inequalities in self-rated health: an inverse odds weighting approach

Objective:Using a novel mediation method that presents unbiased results even in the presence of exposure–mediator interactions, this study estimated the extent to which working conditions and health behaviors contribute to educational inequalities in self-rated health in the workforce.Methods:Respondents of the longitudinal Survey of Health, Ageing, and Retirement in Europe (SHARE) in 16 countries were selected, aged 50–64 years, in paid employment at baseline and with information on education and self-rated health (N=15 028). Education, health behaviors [including body mass index (BMI)] and working conditions were measured at baseline and self-rated health at baseline and two-year follow-up. Causal mediation analysis with inverse odds weighting was used to estimate the total effect of education on self-rated health, decomposed into a natural direct effect (NDE) and natural indirect effect (NIE).Results:Lower educated workers were more likely to perceive their health as poor than higher educated workers [relative risk (RR) 1.48, 95% confidence interval (CI) 1.37–1.60]. They were also more likely to have unfavorable working conditions and unhealthy behaviors, except for alcohol consumption. When all working conditions were included, the remaining NDE was RR 1.30 (95% CI 1.15–1.44). When BMI and health behaviors were included, the remaining NDE was RR 1.40 (95% CI 1.27–1.54). Working conditions explained 38% and health behaviors and BMI explained 16% of educational inequalities in health. Including all mediators explained 64% of educational inequalities in self-rated health.Conclusions:Working conditions and health behaviors explain over half of the educational inequalities in self-rated health. To reduce health inequalities, improving working conditions seems to be more important than introducing health promotion programs in the workforce.     

Effects of aminoglutethimide on delta 5-androstenediol metabolism in postmenopausal women with breast cancer

delta-5-Androstene-3 beta, 17 beta-diol has potential estrogenic activity because it is known to bind to receptors and translocate to the nucleus of certain estrogen target tissues. Its role in the biology of breast cancer is unclear. Aminoglutethimide plus hydrocortisone ("medical adrenalectomy") has been used to treat postmenopausal women with metastatic breast cancer. We studied delta 5-androstene-3 beta, 17 beta-diol metabolism in postmenopausal women with breast cancer before and during aminoglutethimide-plus-hydrocortisone therapy, utilizing the constant infusion technique. The metabolic clearance rate for five subjects was 799 +/- 89 liters/24 hr (470 +/- 47 liters/24 hr/sq m) before and 751 +/- 93 liters/24 hr (444 +/- 57 liters/24 hr/sq m) during therapy. Plasma delta 5-androstene-3 beta, 17 beta-diol and delta 5-androstene-3 beta, 17 beta-diol free index decreased despite absence of change in the metabolic clearance rate. Increased dehydroepiandrosterone/delta 5-androstene-3 beta, 17 beta-diol conversion ratios in individual patients suggested an increase in 17 beta-hydroxysteroid dehydrogenase activity during therapy. There were no alterations in the formation of the estrogen precursors testosterone and delta 4-androstene-3,17-dione.