Results of single‐center screening for chronic hepatitis E in children after liver transplantation and report on successful treatment with ribavirin

RNA screening for HEV in 22 liver‐transplanted children with chronic graft hepatitis out of a cohort of 267 liver‐transplanted children detected a single patient with chronic HEV infection. Although this patient remained viremic for 33 months, anti‐HEV‐IgG was not detectable with MP assay but with Wantai assay. We present the first case of successful ribavirin therapy in an immunosuppressed child with chronic HEV infection. In conclusion, chronic HEV infection in immunosuppressed children may not be detectable employing serological assays. Therefore, the most reliably screening method is screening for HEV‐RNA. Chronic HEV infection in children can successfully be treated with ribavirin.     

The relationship between urban environment and the inflammatory bowel diseases: a systematic review and meta-analysis

ABSTRACT: BACKGROUND: The objective of this study was to conduct a systematic review with meta-analysis of studies assessing the association between living in an urban environment and the development of the Crohn's disease (CD) or ulcerative colitis (UC). METHODS: A systematic literature search of MEDLINE (1950-Oct. 2009) and EMBASE (1980-Oct. 2009) was conducted to identify studies investigating the relationship between urban environment and IBD. Cohort and case-control studies were analyzed using incidence rate ratio (IRR) or odds ratio (OR) with 95 % confidence intervals (CIs), respectively. Stratified and sensitivity analyses were performed to explore heterogeneity between studies and assess effects of study quality. RESULTS: The search strategy retrieved 6940 unique citations and 40 studies were selected for inclusion. Of these, 25 investigated the relationship between urban environment and UC and 30 investigated this relationship with CD. Included in our analysis were 7 case-control UC studies, 9 case-control CD studies, 18 cohort UC studies and 21 cohort CD studies. Based on a random effects model, the pooled IRRs for urban compared to rural environment for UC and CD studies were 1.17 (1.03, 1.32) and 1.42 (1.26, 1.60), respectively. These associations persisted across multiple stratified and sensitivity analyses exploring clinical and study quality factors. Heterogeneity was observed in the cohort studies for both UC and CD, whereas statistically significant heterogeneity was not observed for the case-control studies. CONCLUSIONS: A positive association between urban environment and both CD and UC was found. Heterogeneity may be explained by differences in study design and quality factors.     

The guanylate kinase domain of the beta-subunit of voltage-gated calcium channels suffices to modulate gating

Inactivation of voltage-gated calcium channels is crucial for the spatiotemporal coordination of calcium signals and prevention of toxic calcium buildup. Only one member of the highly conserved family of calcium channel β-subunits—Ca_Vβ—inhibits inactivation. This unique property has been attributed to short variable regions of the protein; however, here we report that this inhibition actually is conferred by a conserved guanylate kinase (GK) domain and, moreover, that this domain alone recapitulates Ca_Vβ-mediated modulation of channel activation. We expressed and refolded the GK domain of Ca_Vβ_2a, the unique variant that inhibits inactivation, and of Ca_Vβ_1b, an isoform that facilitates it. The refolded domains of both Ca_Vβ variants were found to inhibit inactivation of Ca_V2.3 channels expressed in Xenopus laevis oocytes. These findings suggest that the GK domain endows calcium channels with a brake restraining voltage-dependent inactivation, and thus facilitation of inactivation by full-length Ca_Vβ requires additional structural determinants to antagonize the GK effect. We found that Ca_Vβ can switch the inactivation phenotype conferred to Ca_V2.3 from slow to fast after posttranslational modifications during channel biogenesis. Our findings provide a framework within which to understand the modulation of inactivation and a new functional map of Ca_Vβ in which the GK domain regulates channel gating and the other conserved domain (Src homology 3) may couple calcium channels to other signaling pathways.     

Clinical correlation of asbestos bodies in BAL fluid

BACKGROUND: Asbestos bodies (AB) in BAL cells are specific markers of asbestos exposure. METHODS: We retrospectively reviewed BAL cytocentrifuge slides of 30 utility workers with a history of asbestos exposure and 30 normal volunteers. BAL cytocentrifuge slides were blinded and scanned under 40 x light microscope. RESULTS: AB were found more frequently in subjects with a history of asbestos exposure compared to normal volunteers (10 of 30 subjects, 33%, vs 0 of 30 subjects). The mean number of AB seen in the AB-positive group was 2.7 per slide. Demographic data were comparable including age, gender, and smoking. Exposure histories were also similar: duration > 20 years, onset > 30 years ago, and time since last exposure > 7 years. More AB-positive patients reported respiratory symptoms (70% vs 26%, p < 0.05). High-resolution CT scans of AB-positive patients revealed a higher prevalence of parenchymal disease (70% vs 26%, p < 0.05). AB-positive subjects had reduced pulmonary function compared to AB-negative subjects: FVC (86% vs 97% predicted), FEV(1) (77% vs 92% predicted, p < 0.05), and diffusion capacity of the lung for carbon monoxide (76% vs 104% predicted, p < 0.01). CONCLUSION: In individuals with a history of asbestos exposure, the presence of AB in BAL cells is associated with higher prevalence of parenchymal abnormalities, respiratory symptoms, and reduced pulmonary function.