Aim: To investigate the role of Helicobacter pylori, expressing the virulence marker CAGA (cytotoxin associated gene product A) in ulcer complications and its interaction with nonsteroidal anti‐inflammatory drugs (NSAIDs) and other risk factors. Design: Case control study using conditional logistic regression analysis. Setting: University and City Hospitals, Nottingham. Subjects: 203 consecutive patients with ulcer bleeding and 203 age‐ and sex‐matched controls. Results: Ulcer bleeding was more likely with positive H. pylori serology (odds ratio = 3.3, 95% CI: 1.7–6.6 for CagA positive, but only OR = 1.6, 95% CI: 0.7–3.7 for CagA negative serology), current smoking (OR 2.2, 95% CI: 1.04–4.7), aspirin ≤ 300 mg daily (OR 7.7, 95% CI: 2.8–20.6), all other nonsteroidal anti‐inflammatory drugs (NSAIDs: OR 10.6, 95% CI: 3.1–35.7 for ≤ 1 defined daily dose lower and OR 22.6, 95% CI: 6.2–82.0 for higher doses) and past ulcer history (OR 5.6, 95% CI: 2.3–14.1). Aspirin ≤ 300 mg daily was used by 25.1% of patients vs. 7.4% of controls. Smoking only enhanced risk in the presence of H. pylori, with a synergistic interaction (interaction odds ratio = 4.9, 2.4–9.9, P=0.002). Conversely, risks with non‐aspirin NSAIDs were reduced in the presence of H. pylori, particularly if CagA‐positive (interaction odds ratio=0.21, 0.05–0.9, P=0.03). Conclusions: CagA positive H. pylori infection is associated with an increased risk of ulcer bleeding. The risk from non‐aspirin NSAIDs is even higher, but is less in H. pylori infected people. Low‐dose aspirin is now commonly associated with ulcer bleeding.

INTRODUCTIONStandard treatment for severe acute exacerbations of ulcerative colitis has changed little over the last 20 years. The treatment consists of either oral, rectal or intravenous corticosteroids and 5-aminosalicylic acid compounds. Patients who do not respond to this treatment will usually be referred for colectomy. Antimetabolites such as azathioprine and 6-mercaptopurine are effective in corticosteroid-dependent disease, but because of their slow onset of action (mean 4 months) are of limited use for acute exacerbations. Approximately 15% of patients with acute ulcerative colitis will require hospital admission for control of symptoms and up to 40% of these will require colectomy. 1,2 There is preliminary evidence over recent years suggesting that the immunosuppressive drug cyclosporin SUMMARY Background: Recent evidence suggests that the immunosuppressive drug cyclosporin may be of bene®t in treating patients with severe colitis who are steroid resistant. Although cyclosporin appears to be effective in reducing colectomy rates in the short term, few data are available on the long-term follow-up of such patients. Aim: To investigate the short-and long-term outcome of patients with severe steroid-resistant ulcerative colitis treated with cyclosporin who were otherwise being considered for colectomy. Methods: Twenty-two patients with severe steroid-resistant exacerbations of ulcerative colitis who were being considered for colectomy were treated with cyclosporin (4 mg/kg i.v.) daily for 7 days followed by oral treatment (6 mg/kg/day) if colectomy was avoided. Results: Twenty of 22 patients (91%) avoided colectomy during their initial hospital admission. With a mean follow-up period of 39 months (range 31±59), eight of these patients have subsequently relapsed and required

Proton pump inhibitors (PPIs) are drugs which irreversibly inhibit proton pump (H+/K+ ATPase) function and are the most potent gastric acid-suppressing agents in clinical use. There is now a substantial body of evidence showing improved efficacy of PPIs over the histamine H2 receptor antagonists and other drugs in acid-related disorders. Omeprazole 20 mg/day, lansoprazole 30 mg/day, pantoprazole 40 mg/day or rabeprazole 20 mg/day for 2 to 4 weeks are more effective than standard doses of H2-receptor antagonists in healing duodenal and gastric ulcers. Patients with gastric ulcers should receive standard doses of PPIs as for duodenal ulcers but for a longer time period (4 to 8 weeks). There is no conclusive evidence to support the use of a particular PPI over another for either duodenal or gastric ulcer healing. For Helicobacter pylori-positive duodenal ulceration, a combination of a PPI and 2 antibacterials will eradicate H. pylori in over 90% of cases and significantly reduce ulcer recurrence. Patients with H. pylori-positive gastric ulcers should be managed similarly. PPIs also have efficacy advantages over ranitidine and misoprostol and are better tolerated than misoprostol in patients taking nonsteroidal anti-inflammatory drugs (NSAIDs). In endoscopically proven gastro-oesophageal reflux disease, standard daily doses of the PPIs are more effective than H2-receptor antagonists for healing, and patients should receive a 4 to 8 week course of treatment. For severe reflux, with ulceration and/or stricture formation, a higher dose regimen (omeprazole 40 mg, lansoprazole 60 mg, pantoprazole 80 mg or rabeprazole 40 mg daily) appears to yield better healing rates. There is little evidence that PPIs lead to resolution of Barrett's oesophagus or a reduction of subsequent adenocarcinoma development, but PPIs are indicated in healing of any associated ulceration. In Zollinger-Ellison syndrome, PPIs have become the treatment of choice for the management of gastric acid hypersecretion.

No abstract

The epithelium of the gastrointestinal tract transports ions and water but excludes luminal microorganisms and toxic molecules. The factors regulating these important functions are not fully understood. Intestinal myofibroblasts lie subjacent to the basement membrane, at the basal surface of epithelial cells. We recently showed that primary cultures of adult human colonic subepithelial myofibroblasts express cyclooxygenase (COX)-1 and COX-2 enzymes and release bioactive transforming growth factor-β (TGF-β). In this study we have investigated the role of normal human colonic subepithelial myofibroblasts in the regulation of transepithelial resistance and secretory response in HCA-7 and T84 colonic epithelial cell lines. Cocultures of epithelial cells-myofibroblasts and medium conditioned by myofibroblasts enhanced transepithelial resistance and delayed mannitol flux. A panspecific antibody to TGF-β (but not piroxicam) antagonized this effect. In HCA-7 cells, myofibroblasts downregulated secretagogue-induced change in short-circuit current, and this effect was reversed by pretreatment of myofibroblasts with piroxicam. In contrast to HCA-7 cells, myofibroblasts upregulated the agonist-induced secretory response in T84 cells. This study shows that intestinal subepithelial myofibroblasts enhance barrier function and modulate electrogenic chloride secretion in epithelial cells. The enhancement of barrier function was mediated by TGF-β. In contrast, the modulation of agonist-induced change in short-circuit current was mediated by cyclooxygenase products. These findings suggest that colonic myofibroblasts regulate important functions of epithelial cells via distinct secretory products.