OJGSUMMARY. Healthy adult volunteers received either single or repeated 3-g doses of amoxycillin by mouth at weekly intervals on three occasions. The salivary flora of each volunteer was monitored before, during and up to 11 weeks after the final dose of antibiotic. Viable counts of anaerobic bacteria, streptococci and streptococci resistant to amoxycillin 2 mg/L and 40 mg/L were determined in samples of saliva. All 20 volunteers harboured low numbers of streptococci resistant to amoxycillin 2 mg/L (mean count = 6.57 x lo3 cfu/ml of saliva) before administration of the antibiotic; much lower carriage rates (45%) were observed for bacteria resistant to amoxycillin 40 mg/L (mean count = 1 16 cfu/ml of saliva). Each dose of amoxycillin had a rapid but transient effect on the numbers of salivary bacteria. A placebo lacking the antibiotic had no effect. A single 3-g dose of amoxycillin had little or no effect on the numbers of resistant streptococci and, therefore, it was concluded that in patients at risk of infective endocarditis a second prophylactic dose would not be invalidated. The numbers of resistant streptococci increased significantly after the second and third doses of amoxycillin, and persisted for 4 7 weeks. Consequently, in at-risk patients requiring repeated dental procedures liable to produce bacteraemia, either alternative antibiotic regimens should be used each time or intervals of at least 4 weeks should be left between treatment sessions.
Aims/hypothesis SMAD proteins are involved in multiple signalling pathways and are key modulators of gene expression. We hypothesised that genetic variation in selected SMAD genes contributes to susceptibility to diabetic nephropathy. Methods We selected 13 haplotype tag (ht) single nucleotide polymorphisms (SNPs) from 67 variants identified by resequencing the SMAD2 and SMAD3 genes. For SMAD1, SMAD4 and SMAD5 genes, genotype data were downloaded for 217 SNPs from Phase II of the International HapMap project. Of these, 85 SNPs met our inclusion criteria, resulting in the selection of 13 tag SNPs for further investigation. A case-control approach was employed, using 267 nephropathic patients and 442 controls with type 1 diabetes from Ireland. Two further populations (totalling 1,407 patients, 2,238 controls) were genotyped to validate initial findings. Genotyping was conducted using iPLEX, TaqMan and gel electrophoresis. Results The distribution of genotypes was in HardyWeinberg equilibrium. Analysis by the χ 2 test of genotype and allele frequencies in patients versus controls in the Irish population (n=709) revealed evidence for the association of one allele at 5% level of significance (rs10515478, p uncorrected =0.006; p corrected =0.04). This finding represents a relatively small difference in allele frequency of 6.4% in the patient group compared with 10.7% in the control group; this difference was not supported in subsequent investigations using DNA from European individuals with similar phenotypic characteristics. Conclusions/interpretation We selected an appropriate subset of variants for the investigation of common genetic risk factors and assessed SMAD1 to SMAD5 genes for association with diabetic nephropathy. We conclude that common polymorphisms in these genes do not strongly influence genetic susceptibility to diabetic nephropathy in white individuals with type 1 diabetes mellitus.
Background: Chronic obstructive pulmonary disease (COPD) and tobacco use are leading causes of morbidity and mortality. The prevalence and clinical impact of COPD on mortality and kidney transplantation among patients who begin dialysis therapy is unclear. Methods: We explored the clinical impact of COPD and continued tobacco use on overall mortality and kidney transplantation in a national cohort study of US dialysis patients. National data on all dialysis patients (n = 769,984), incident between May 1995 and December 2004 and followed until October 31, 2006, were analyzed from the United States Renal Data System. Prevalence and period trends were determined while multivariable Cox regression evaluated relative hazard ratios (RR) for death and kidney transplantation. Results: The prevalence of COPD was 7.5% overall and increased from 6.7 to 8.1% from 1995–2004. COPD correlated significantly with older age, cardiovascular conditions, cancer, malnutrition, poor functional status, and tobacco use. Adjusted mortality risks were significantly higher for patients with COPD (RR = 1.20, 95% CI 1.18–1.21), especially among current smokers (RR = 1.28, 95% CI 1.25–1.32), and varied inversely with advancing age. In contrast, the adjusted risks of kidney transplantation were significantly lower for patients with COPD (RR = 0.47, 95% CI 0.41–0.54, for smokers and RR = 0.54, 95% CI 0.50–0.58, for non-smokers) than without COPD [RR = 0.72, 95% CI 0.70–0.75, for smokers and RR = 1.00 for non-smokers (referent category)]. Conclusions: Patients with COPD who begin dialysis therapy in the US experience higher mortality and lower rates of kidney transplantation, outcomes that are far worse among current smokers.
BK virus nephropathy (BKVN) is a well-recognized complication of renal transplantation. Several cases of native kidney BKVN following other solid organ or bone marrow transplants have been reported. We describe a patient with chronic lymphocytic leukaemia who presented with deteriorating renal function with no history of solid organ or bone marrow transplantation. Renal biopsy demonstrated tubular injury characteristic of viral infection, confirmed as BK virus by immunohistochemistry and elevated serum BK viral titres. Treatment with leflunomide reduced serum viral titres and stabilized renal function. This is the first biopsy-proven case of native kidney BKVN in a patient with no previous transplantation history.
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