Ulcerative Colitis: Koch S

Weber A, Fein F, Koch S, Dupont-Gossart AC, Mantion G, Heyd B, Carbonnel F. · Service de Gastroentérologie et Nutrition, Hôpital Universitaire, F-25000 Besançon, France. · Inflamm Bowel Dis. · Pubmed #17119387 links to  free full text

Abstract: BACKGROUND: Intravenous cyclosporine is active in 60% to 80% of patients with ulcerative colitis (UC) who failed to respond to intravenous corticosteroids. Several studies have suggested that cyclosporine in microemulsion form (Neoral) has some efficacy in this setting, but the optimal dose, blood level, time to response, and remission need to be better defined. The aim of this study was to evaluate the response to Neoral and its toxicity in active corticosteroid-refractory UC. METHODS: Between March 2002 and August 2005, 20 courses of Neoral [initial dose, 2.3 mg/kg (range, 1.8 to 2.8 mg/kg) every 12 hours] were prescribed in 19 consecutive patients for a UC attack that did not respond to intravenous methylprednisolone. All patients received prophylaxis against Pneumocystis carinii. RESULTS: Response was obtained in 17 of 20 attacks (85%) after 3.5 days (range, 1 to 7). Remission was obtained in 15 of 20 attacks (75%) after 13 days (range, 2 to 30 days). Four responders relapsed and underwent colectomy 21 to 900 days after the start of Neoral. Overall, 14 of 19 patients (74%) were colectomy free after a median follow-up of 8 months (range, 1 to 41 months). Cyclosporine blood levels were measured at fasting (C0) and 2 hours after Neoral administration (C2) in a subgroup of 10 responders. The results were 103 ng/mL (range, 32 to 240 ng/mL) for C0 and 761 ng/mL (183 to 1390 ng/mL) for C2. One severe bedridden patient with neonatal encephalopathy died. Main side effects observed were mild transient renal impairment (n = 2), hypertension (n = 1), cytomegalovirus infection (n = 2), and esophageal candidiasis (n = 1). CONCLUSIONS: In active corticosteroid-refractory UC, Neoral seems to have the same efficacy and toxicity as the intravenous form. Trough target cyclosporine blood levels should not exceed 100 ng/mL for C0 and 700 ng/mL for C2.

Swidsinski A, Loening-Baucke V, Theissig F, Engelhardt H, Bengmark S, Koch S, Lochs H, Dörffel Y. · Humboldt University, Charité, CCM, 10098 Berlin, Germany. · Gut. · Pubmed #16908512 No free full text.

Abstract: AIM: To study the role of mucus in the spatial separation of intestinal bacteria from mucosa. PATIENTS AND METHODS: Mucus barrier characteristics were evaluated using histological material obtained by biopsy from purged colon, colon prepared with enema and material from untreated appendices fixed with non-aqueous Carnoy solution. Bacteria were evaluated using fluorescence in situ hybridization, with bacterial 16S RNA probes and related to the periodic acid Schiff alcian blue stain. Biopsies from controls (n = 20), patients with self-limiting colitis (SLC; n = 20), ulcerative colitis (n = 20) and 60 randomly selected appendices were investigated. RESULTS: The mucosal surface beneath the mucus layer was free of bacteria in > or =80% of the normal appendices and biopsies from controls. The thickness of the mucus layer and its spread decreased with increasing severity of the inflammation; the epithelial surface showed bacterial adherence, epithelial tissue defects and deep mucosal infiltration with bacteria and leucocytes. Bacteria and leucocytes were found within mucus in all biopsy specimens from patients with ulcerative colitis, SLC, and acute appendicitis. The concentration of bacteria within mucus was inversely correlated to the numbers of leucocytes. CONCLUSIONS: The large bowel mucus layer effectively prevents contact between the highly concentrated luminal bacteria and the epithelial cells in all parts of the normal colon. Colonic inflammation is always accompanied by breaks in the mucus barrier. Although the inflammatory response gradually reduces the number of bacteria in mucus and faeces, the inflammation itself is not capable of preventing bacterial migration, adherence to and invasion of the mucosa.