S Sitaraman

Improved patient survival after acute variceal bleeding: a multicenter, cohort study

OBJECTIVE:Existing literature indicates that the mortality rate with each variceal bleeding episode is 30–50%. Over the past 2 decades, there have been significant developments in the management of variceal bleeding. The effect of these developments on the natural history of variceal bleeding is unclear. Therefore, a retrospective, multicenter study was conducted to define the outcomes of variceal bleeding and to describe the patterns of current practice in the management of variceal bleeding.METHODS:All patients with documented variceal bleeding hospitalized at four large county hospitals from January 1, 1997, to June 30, 2000, were included. Study outcomes were in-hospital, 6-wk, and overall mortality, rate of rebleeding, transfusion requirement, and length of stay. After discharge, patients were followed until death or study closure date, on June 30, 2000.RESULTS:A total of 231 subjects were included, and their in-hospital, 6-wk, and overall mortality rates were 14.2%, 17.5%, and 33.5%, respectively. The frequency of rebleeding during follow-up was 29%. Median length of total hospital stay was 8 days (0–34 days). Median number of packed red cell units transfused was 4 U (0–60 U). Upper endoscopy was performed in 95% of patients within 24 h, and endoscopic therapy was done in all but eight patients (ligation 64%, sclerotherapy 33%). Octreotide was administered in 74% of the patients. Portasystemic shunts were performed in 7.5% of the patients for controlling acute variceal bleeding.CONCLUSIONS:The mortality rate after variceal bleeding in this study was substantially lower than previously reported. This suggests that advances made in the management of variceal bleeding have improved outcomes after variceal bleeding.

Invasive Escherichia coli are a feature of Crohn's disease.

Crohns disease (CD) and ulcerative colitis (UC) are idiopathic inflammatory conditions of the gut. Our goal was to investigate if invasive Escherichia coli strains were present in patients with inflammatory bowel disease (IBD). Bacterial strains were isolated from biopsy material obtained from normal controls, and patients with a clinical diagnosis of CD and UC. Invasive bacteria were characterized by gentamicin protection assay and biochemical profiling (Api-20E). Strains were characterized by induction of cytokine expression in epithelial and macrophage cell cultures, measurement of epithelial barrier function, and confocal microscopy. Of all invasive bacterial strains in CD 98.9% were identified as E. coli as opposed to 42.1% in UC and 2.1% in normal controls. Epithelial invasion in vitro was significantly higher for CD-associated E. coli (8.4%, ±5.5 of initial inoculum (I/O)) in comparison to UC (2.5%, ±0.4 I/O), but highest for strains from inflamed CD tissue (11.3%, ±4.3 I/O). Both, CD and UC E. coli strains induced high mean TNF-α expression in macrophage cell lines (2604.8 pg/105 cells, ±447.4; 2,402.6 pg/105 cells, ±476.3, respectively), but concentrations were significantly higher for isolates from inflamed CD tissue (3071.3 pg/105 cells, ±226.0). Invasive E. coli from IBD tissue induced similar concentrations of interleukin (IL)-8 in epithelial cell cultures, but strains from inflamed CD tissue induced significantly less epithelial IL-8 (674.1 pg/105 cells, ±58.0 vs 920.5 pg/105 cells, ±94.6). IBD-associated E. coli strains significantly decreased transepithelial resistance, induced disorganization of F-actin and displacement of ZO-1, and E-cadherin from the apical junctional complex (AJC). In comparison to normal controls and UC, E. coli are more prevalent in CD, are highly invasive, and do not encode for known effector proteins. E. coli strains from IBD patients regulate cytokine expression and epithelial barrier function, two pathological features of IBD.

Melatonin and ulcerative colitis: Evidence, biological mechanisms, and future research

&NA; Ulcerative colitis (UC) is an inflammatory bowel disease that afflicts up to 1 million people in the US. Current treatments for UC are mostly nonspecific, not always effective, and often accompanied by serious side effects. Therefore, there is considerable interest in finding alternative and more tolerable treatments for this disease. Physiologic data suggest that melatonin is an important regulator of both inflammation and motility in the gastrointestinal tract, and data from in vitro studies, animal experiments, and limited studies in humans suggest that supplemental melatonin may have an ameliorative effect on colitis. In this review we summarize the evidence regarding melatonin as a possible therapeutic agent in UC and discuss possible biological mechanisms and directions for future research.

PepT1 mediated tripeptide KPV uptake reduces intestinal inflammation: P-078.

and IKK , the catalytic subunits of the IKK signalosome that phosphorylates I B . DSS had greater effect on reduction of Hsp27 phosphorylation than CGN, and Tempol had less effect on CGN-induced activation of IL-8. In contrast to DSS, CGN exposure also activated an innate immune pathway of inflammation mediated by TLR4 and Bcl10. Bcl10 is a caspase-recruitment domain (CARD) containing protein, similar to NOD2, and is well-recognized to mediate a pathway of innate immune inflammatory response in lymphocytes and macrophages. In the IEC, Bcl10 co-immunoprecipitated with IKKã (also called Nemo), the regulatory domain of the IKK signalosome. CGN exposure produced an increase in the ubiquitination of Nemo; increased Nemo ubiquitination is associated with increased phospho-I B , leading to increased nuclear localization of NF B and increased secretion of IL-8. Bcl10 was not increased following exposure to DSS, and silencing of Bcl10 had no impact on DSS-induced activation of IL-8. The study results demonstrate that DSS generates greater increase in ROS than CGN at a comparable level of exposure, but that CGN also activates an immune responsive pathway through Bcl10 that is not induced by DSS. CGN appears to activate a pathway of innate immunity, due to its unusual á-1,3-galactosidic linkage that is immunogenic. In contrast to CGN, which is widely used as a food additive in the Western diet, DSS is not incorporated into the Western diet. Further elucidation of these mechanisms that model IBD may provide new insights into prevention and treatment of clinical IBD. Since the food additive CGN activates pathways of inflammation that involve innate immunity, as well as increased ROS, increased attention to its elimination from the diet is indicated.