Blastomycosis during pregnancy.

Disseminated blastomycosis with extensive involvement of the lungs, skin and bones was diagnosed in a 31-year-old woman who was 36 weeks pregnant. No antifungal treatment had been given while she was pregnant, and she gave birth shortly after admission to hospital. The child was healthy and uninfected, and there were no signs of inflammation or infection in the placenta. Post partum the mother was treated with 2 g of amphotericin B, with resolution of her symptoms. A literature review suggested that blastomycosis and other systemic fungal infections are more likely to occur during pregnancy because of immunosuppression and that disseminated blastomycosis in pregnant women should be treated with amphotericin B.     

Determining possible thrombus sites in an extracorporeal device,using computational fluid dynamics-derived relative residence time

The prediction of conditions that may result in thrombus formation is a useful application of computational fluid dynamics. A number of techniques exist, based on the consideration of wall shear stress and regions of low blood flow; however, no clear guideline exists for the best practice of their use. In this paper, the sensitivity of each parameter and the specific mechanical forces are explained, before the optimal indicator of thrombosis risk is outlined. An extracorporeal access device cavity provides a suitable geometry to test the methodology. The recommended method for thrombus prediction considers areas with a calculated residence time (RT) and shear strain rate (SSR) thresholds, here set to RT>1 and SSR < 10 s^? 1. Evidence of thrombosis was found for physiological waveforms with an absence of reverse flow, which is expected to ‘wash out’ the cavity. The predicted thrombosis sites compare well with evidence collected from explanted devices.     

Smoking-mediated up-regulation of GAD67 expression in the human airway epithelium

Background

The production of gamma-amino butyric acid (GABA) is dependent on glutamate decarboxylases (GAD65 and GAD67), the enzymes that catalyze the decarboxylation of glutamate to GABA. Based on studies suggesting a role of the airway epithelial GABAergic system in asthma-related mucus overproduction, we hypothesized that cigarette smoking, another disorder associated with increased mucus production, may modulate GABAergic system-related gene expression levels in the airway epithelium.

Methods

We assessed expression of the GABAergic system in human airway epithelium obtained using bronchoscopy to sample the epithelium and microarrays to evaluate gene expression. RT-PCR was used to confirm gene expression of GABAergic system gene in large and small airway epithelium from heathy nonsmokers and healthy smokers. The differences in the GABAergic system gene was further confirmed by TaqMan, immunohistochemistry and Western analysis.

Results

The data demonstrate there is a complete GABAergic system expressed in the large and small human airway epithelium, including glutamate decarboxylase, GABA receptors, transporters and catabolism enzymes. Interestingly, of the entire GABAergic system, smoking modified only the expression of GAD67, with marked up-regulation of GAD67 gene expression in both large (4.1-fold increase, p < 0.01) and small airway epithelium of healthy smokers (6.3-fold increase, p < 0.01). At the protein level, Western analysis confirmed the increased expression of GAD67 in airway epithelium of healthy smokers compared to healthy nonsmokers (p < 0.05). There was a significant positive correlation between GAD67 and MUC5AC gene expression in both large and small airway epithelium (p < 0.01), implying a link between GAD67 and mucin overproduction in association with smoking.

Conclusions

In the context that GAD67 is the rate limiting enzyme in GABA synthesis, the correlation of GAD67 gene expression with MUC5AC expressions suggests that the up-regulation of airway epithelium expression of GAD67 may contribute to the increase in mucus production observed in association with cigarette smoking.

Trial registration

NCT00224198; NCT00224185