Enterohemorrhagic Escherichia coli suppresses inflammatory response to cytokines and its own toxin.

Infection with the enteric pathogen enterohemorrhagic Escherichia coli (EHEC) causes a variety of symptoms ranging from nonbloody diarrhea to more severe sequelae including hemorrhagic colitis, altered sensorium and seizures, and even life-threatening complications, such as hemolytic uremic syndrome and thrombotic thrombocytopenic purpura. The more severe consequences of EHEC infection are attributable to the production of Shiga toxin (Stx) and its subsequent effects on the vasculature, which expresses high levels of the Stx receptor, Gb3. Interestingly, the intestinal epithelium does not express Gb3. Despite the lack of Gb3 receptor expression, intestinal epithelial cells translocate Stx. The effect of Stx on intestinal epithelial cells is controversial with some studies demonstrating induction of inflammation and others not. This may be difficult to resolve because EHEC expresses both proinflammatory molecules, such as flagellin, and factor(s) that dampen the inflammatory response of epithelial cells. The goal of our study was to define the effect of Stx on the inflammatory response of intestinal epithelial cells and to determine whether infection by EHEC modulates this response. Here we show that Stx is a potent inducer of the inflammatory response in intestinal epithelial cells and confirm that EHEC attenuates the induction of IL-8 by host-derived proinflammatory cytokines. More importantly, however, we show that infection with EHEC attenuates the inflammatory response by intestinal epithelial cells to its own toxin. We speculate that the ability of EHEC to dampen epithelial cell inflammatory responses to Stx and cytokines facilitates intestinal colonization.

Role of echocardiography in detecting portopulmonary hypertension in liver transplant candidates.

Portopulmonary hypertension (PPHTN) is a recognized complication of end-stage liver disease that adversely affects the outcome of orthotopic liver transplantation (OLT). There are limited data on the role of Doppler echocardiography in assessing pulmonary artery systolic pressure (PASP) in this population. The purpose of our study was to examine the accuracy of Doppler echocardiography in evaluating pulmonary artery pressures in liver transplant candidates. Clinical and demographic data were gathered retrospectively for 78 liver transplant candidates (48 men and 30 women, mean age 51 +/- 9.6 yr) who had PASP determined both by right heart catheterization (RHC) and echocardiography. Paired sample t-test was used to compare mean PASP by echocardiography and RHC. Correlation of PASP between echocardiography and RHC was determined using Pearson's linear correlation. Positive and negative predictive values for echocardiography for PASP > 50 mmHg are reported as compared with RHC. The mean PASP by echocardiography (43.2 +/- 12.3 mm Hg) was significantly higher than mean PASP by RHC (33.7 +/- 15.5 mm Hg; P <.001). Regarding PASP, there was a significant but weak correlation between echocardiography and RHC (r = 0.46, P =.01). The positive and negative predictive values of echocardiography for identifying clinically significant pulmonary hypertension (PASP > 50 mm Hg) were 37.5% and 91.9%, respectively. Echocardiography is a useful tool in estimating PASP in liver transplant candidates. Patients with apparently elevated PASP by echocardiography should undergo invasive assessment by RHC before being excluded from liver transplant.