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Laish I.,Gastroenterology and hepatology institute
Harefuah | Year: 2012

Thiopurine drugs, azathioprine (Imuran) and 6-mercaptopurine (6-MP), are immunomodulators that have been shown to be effective at inducing and maintaining remission in inflammatory bowel disease. Although usually well-tolerated, the occurrence of side effects, typically myelotoxicity and hepatotoxicity, is a major drawback. The side effects can be classified as dose-dependent and independent. Both cholestatic hepatitis and endothelial injury, leading to vascular congestion and nodular regenerative hyperplasia, have been described during therapy with thiopurines, which can end up with portal hypertension. These injuries are potentially mediated by different metabolites. In this article we present a case of hyperammonaemic encephalopathy during therapy with 6-MP, possibly the first recorded in the literature, which probably resulted from the combination of thiopurine-induced liver injury with portal hypertension and the presence of spontaneous portosystemic venous shunts.

Zigmond E.,Weizmann Institute of Science | Zigmond E.,Gastroenterology and hepatology institute | Jung S.,Weizmann Institute of Science
Trends in Immunology | Year: 2013

Macrophages are the most abundant mononuclear phagocytes in the healthy intestinal lamina propria and have emerged as crucial sentinels for the maintenance of tissue homeostasis. Matching the dynamic mucosal landscape, CX3C chemokine receptor (CX3CR)1-expressing macrophages are relatively short lived, and as opposed to most other tissue macrophages, are continuously replaced from blood monocytes that acquire in the healthy tissue context a robust noninflammatory gene expression signature. By contrast, during gut inflammation, monocytes differentiate in the gut into proinflammatory effector cells, as well as migratory antigen-presenting cells. Manipulation of monocyte fates in the intestine might hold promise for the disease management of inflammatory bowel disorders. © 2013 Elsevier Ltd.

Kopelman D.,Technion - Israel Institute of Technology | Kopelman Y.,Gastroenterology and hepatology institute | Peled D.,Niti Surgical Solutions | Willenz U.,Lahav Research Institute | And 2 more authors.
Surgical Innovation | Year: 2013

Background: There are limited large animal models for the research of novel anastomotic technologies. Subtotal colectomy requires the anastomosis of relatively remote segments of the alimentary tract that are different anatomically, histologically, and pose significant physiological challenge. The quest for a foreign material-free anastomotic line reintroduced nitinol compression anastomosis into clinical use in the last decade. Objective: To evaluate the safety, histological, and physiological parameters of side-to-side ileocolic nitinol compression anastomosis in a newly developed large animal model, mimicking the human subtotal colectomy. Intervention: Resection of the entire spiral colon with an ileocolic side-to-side compression anastomosis in 12 animals, compared to resection of a short ileal segment in 6 animals. All anastomoses were constructed by using a novel nitinol-based compression device. The animals were followed up to 30 days postoperatively and were reoperated and sacrificed. Results: All 12 animals underwent successful subtotal colectomy with side-to-side nitinol compression anastomosis. No signs of abdominal infection were found. The increase in the colectomized animals' bodyweight over the postoperative course was significantly lower and the animals presented with longer periods of diarrhea. The histopathology revealed minimal inflammation and foreign body reaction with good alignment of the bowel wall layers in both groups. The anastomotic line width was shown to be reduced during the healing course of the compression anastomoses. Conclusions: Side-to-side nitinol compression anastomosis is safe and demonstrates favorable functional and histopathological features. The porcine model of subtotal colectomy can be used for further research of novel anastomotic technologies. © The Author(s) 2013.

Bar-On L.,Weizmann Institute of Science | Zigmond E.,Weizmann Institute of Science | Zigmond E.,Gastroenterology and hepatology institute | Jung S.,Weizmann Institute of Science
Seminars in Immunology | Year: 2011

Inflammatory bowel diseases (IBDs) including Crohn's disease and ulcerative colitis represent a major challenge to clinicians and immunologists trying to understand why in certain individuals the peaceful coexistence of the commensal microflora and its host breaks down and results in chronic inflammation. Here we summarize the recent progress in our understanding of the organization of the intestinal mononuclear phagocytes with dendritic cells and macrophages of distinct phenotype, origin and function. Finally, we discuss potential strategies to translate the recent findings into the management of chronic inflammation in animal models of IBD. © 2011 Elsevier Ltd.

Reddy K.R.,University of Pennsylvania | Shiffman M.L.,Health News | Rodrigueztorres M.,Fundacion de Investigacion De Diego Santurce | Cheinquer H.,Hospital de Clinicas de Porto Alegre | And 8 more authors.
Gastroenterology | Year: 2010

Background & Aims Patients infected with hepatitis C virus (HCV) genotype 1, body weight <85 kg, and high baseline viral load respond poorly to standard doses of pegylated interferon (peginterferon) and ribavirin. We evaluated intensified therapy with peginterferon alfa-2a plus ribavirin. Methods This double-blind randomized trial included HCV genotype 1-infected outpatients from hepatology clinics with body weight <85 kg and HCV RNA titer <400,000 IU/mL. Patients were randomized to 180 μg/wk peginterferon alfa-2a for 48 weeks plus 1200 mg/day ribavirin (standard of care) (group A, n = 191) or 1400/1600 mg/day ribavirin (group B, n = 189). Additional groups included 360 μg/wk peginterferon alfa-2a for 12 weeks then 180 μg/wk peginterferon alfa-2a for 36 weeks plus 1200 mg/day ribavirin (group C, n = 382) or 1400/1600 mg/day ribavirin (group D, n = 383). Follow-up lasted 24 weeks after treatment. Results Sustained virologic response rates (HCV RNA level <15 IU/mL at end of follow-up) in groups A, B, C, and D were 38%, 43%, 44%, and 41%, respectively. There were no significant differences among the 4 groups or between pooled peginterferon alfa-2a regimens (A + B vs C + D: odds ratio [OR], 1.08; 95% confidence interval [CI], 0.831.39; P = .584) or pooled ribavirin regimens (A + C vs B + D: OR, 1.00; 95% CI, 0.791.28; P = .974). Conclusions In patients infected with HCV genotype 1 who are difficult to treat (high viral load, body weight <85 kg), a 12-week induction regimen of peginterferon alfa-2a and/or higher-dose ribavirin is not more effective than the standard regimen. © 2010 AGA Institute.

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