Sperm proteome mapping of a patient who experienced failed fertilization at IVF reveals altered expression of at least 20 proteins compared with fertile donors: case report

The aim of this study was to compare the sperm protein expression profile (proteome map) from a patient who experienced failed fertilization at IVF with fertile controls. One patient and three fertile donor sperm samples were characterized using two-dimensional electrophoresis. Differences in protein expression were established using gel analysis software before attempted protein identification. Gel analysis of the fertile donor proteome maps revealed excellent reproducibility as well as very low intra-donor and inter-donor variability in the presence of protein spots. In the patient samples, we have noted 20 consistent differences in protein expression (six spots missing, three additional spots, four less abundant, seven more abundant) compared with the controls. Two proteins that were more intense in the patient have been conclusively identified as secretory actin-binding protein and outer dense fibre protein 2/2. In conclusion proteome variation between different fertile donors was very low. In contrast, the patient proteome exhibited 20 differences compared with controls, which we believe is an underestimate. These proteins merit further investigation to determine whether failed fertilization at IVF might be caused by abnormalities in their expression. This case report represents a proof of principle that proteomics may be useful to study defects in sperm function.     

Antiretroviral drug treatment interruption in human immunodeficiency virus-infected adults: Clinical and pathogenetic implications for the central nervous system

Interruption of antiretroviral treatment provides a well-defined 'experimental' paradigm to study the dynamics of central nervous system (CNS) infection and host responses in relation to those of systemic infection. We review our experience with 12 subjects (9 who were viremic and three with suppressed infection at baseline) followed longitudinally with serial lumbar punctures and neurological evaluations after stopping their antiretroviral treatments. All but two subjects exhibited an increase in cerebrospinal fluid (CSF) HIV RNA. Approximately half of the cohort developed a substantial, though asymptomatic, CSF lymphocytic pleocytosis with CSF counts rising to 30-60 cells/microL in five of the subjects. Subjects with higher CSF cell counts exhibited higher CSF HIV concentrations. We interpret the relationship of CSF HIV concentrations and pleocytosis in the context of a simple model of virus and cell exchange between blood and CSF. The proportionally greater increase in CSF HIV after treatment interruption indicates that CSF HIV infection is often more effectively suppressed by combination antiretroviral therapy than is systemic infection.     

Systematic review: Antacids,H2-receptor antagonists,prokinetics, bismuth and sucralfate therapy for non-ulcer dyspepsia

BACKGROUND: Evidence for the effectiveness of antacids, histamine-2 receptor antagonists, bismuth salts, sucralfate and prokinetic therapy in non-ulcer dyspepsia is conflicting. AIM: To conduct a systematic review evaluating these therapies in non-ulcer dyspepsia. METHODS: Electronic searches were performed using the Cochrane Controlled Trials Register, Medline, EMBASE, Cinahl and SIGLE until September 2002. Dyspepsia outcomes were dichotomized into cured/improved vs. same/worse. RESULTS: Prokinetics [14 trials, 1053 patients; relative risk reduction (RRR), 48%; 95% confidence interval (95% CI), 27-63%] and histamine-2 receptor antagonists (11 trials, 2164 patients; RRR, 22%; 95% CI, 7-35%) were significantly more effective than placebo. Bismuth salts (RRR, 40%; 95% CI, - 3% to 65%) were superior to placebo, but this was of marginal statistical significance. Antacids and sucralfate were not statistically significantly superior to placebo. A funnel plot suggested that the prokinetic and histamine-2 receptor antagonist results could be due to publication bias. CONCLUSIONS: The meta-analyses suggest that histamine-2 receptor antagonists and prokinetics are superior to placebo. These data are difficult to interpret, however, as funnel plot asymmetry suggests that the magnitude of the effect could be due to publication bias or other heterogeneity-related issues.