Gastric acid prevents bacterial colonization of the stomach and suppression of its secretion might predispose to Clostridium difficile (CD) diarrhoea. We retrospectively studied elderly patients admitted to medical wards of an acute hospital to determine whether the incidence of CD diarrhoea was greater among those previously treated with gastric acid suppressants. From records of stool CD toxin tests undertaken in 1995 and 1996, we found 126 cases with positive results, and selected 126 controls with negative results. Information about pre-morbid illness, predisposing factors for CD and medication received in the preceding 16 weeks was obtained from case-notes. A greater number of CD positive cases had received antibiotics such as Cefuroxime, ciprofloxacin or macrolides with or without metronidazole, were more severely disabled, required assistance for feeding, or had hypoalbuminaemia before the onset of diarrhoea. A greater number of controls had received lactulose, suggesting either that its laxative effect resembled CD infection prompting frequent stool tests, or that it offered protection against CD in this group. Both groups were similar for the use of proton-pump inhibitors or H2-receptor antagonists, suggesting that susceptible elderly patients are not more likely to develop CD diarrhoea after receiving gastric acid suppression therapy.
A total of 854 patients with GI-NET metastases on presentation underwent 392 PTRs. Liver metastases occurred in 430 patients; 240 received liver treatment(s). PTR improved OS in patients with untreated metastases (median survival 10 vs 38 months, P < 0.001). On MV analysis adjusted for demographics, tumor stage, grade, chemotherapy use, Charlson comorbidity index, primary tumor location, or treatment of liver metastases, PTR with/without liver treatment improved OS in comparison to no treatment [hazard ratio (HR) 0.50, P < 0.001 and 0.39, P < 0.001, respectively]. PTR offered a survival benefit across all grades (low-grade, HR 0.38, P = 0.002 and high-grade, HR 0.62, P = 0.025) CONCLUSION:: PTR in GI-NET is associated with a better survival, with or without liver treatment, irrespective of grade. This study supports the resection of the primary tumor in patients with metastatic GI-NETs, independent of liver treatment.
Introduction Mutations in known predisposition genes account for only about a third of all multiple-case breast cancer families. We hypothesized that germline mutations in FANCD2, BRIP1/ BACH1, LMO4 and SFN may account for some of the unexplained multiple-case breast cancer families.
In this review, we highlight the physical and enzymatic properties of the novel human sulfotransferase, SULT4A1. The gene is most highly expressed in selective regions of the brain, although work to date has failed to identify any specific endogenous substrate for the enzyme. SULT4A1 shares low homology with other human sulfotransferases. Nevertheless, it is highly conserved between species. Despite the low homology, it is structurally very similar to other cytosolic sulfotransferases with a conserved substrate binding domain, dimerization site and partial cofactor binding sites. However, the catalytic cavity is much smaller, and it has been suggested that the cofactor may not be accommodated within it. A recent link between variability in the 5'UTR of the SULT4A1 gene and schizophrenia has heightened interest in the endogenous function of the enzyme and its possible role in human disease.
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