Objective-To determine whether azathioprine can prevent relapse in ulcerative colitis.Design-One year placebo controlled double blind trial of withdrawal or continuation of azathioprine.Setting-Outpatient clinics of five hospitals. Subjects-79 patients with ulcerative colitis who had been taking azathioprine for six months or more. Patients in full remission for two months or more (67), and patients with chronic low grade or corticosteroid dependent disease (12) were randomised separately. 33 patients in remission received azathioprine and 34 placebo; five patients with chronic stable disease received azathioprine and seven placebo.Main outcome measure-Rate of relapse. Relapse was defined as worsening of symptoms or sigmoidoscopic appearance.Results-For the remission group the one year rate of relapse was 36% (12/33) for patients continuing azathioprine and 59% (20/34) for those taking placebo (hazard rate ratio 0-5, 95% confidence interval 0 25 to 1-0). For the subgroup of 54 patients in long term remission (greater than six months before entry to trial) benefit was still evident, with a 31% (8/26) rate of relapse with azathioprine and 61% (17/28) with placebo (p<001). For the small group of patients with chronic stable colitis (six were corticosteroid dependent and six had low grade symptoms) no benefit was found from continued azathioprine therapy. Adverse events were minimal.Conclusions-Azathioprine maintenance treatment in ulcerative colitis is beneficial for at least two years if patients have achieved remission while taking the drug. Demonstration of the relapse preventing properties of azathioprine has implications for a large number of patients with troublesome ulcerative colitis, who may benefit from treatment with azathioprine.

Infliximab is not superior to placebo in preventing clinical recurrence after CD-related resection. However, infliximab does reduce endoscopic recurrence. ClinicalTrials.gov ID NCT01190839.

The effect offish oil on the course ofulcerative colitis was investigated in a randomised blinded controlied study. Eighty seven patients received supplements of 20 ml HiEPA fish oil as triglyceride (4.5 g of eicosapentaenoic acid) or olive oil placebo daily for one year. The oils were given in addition to standard drug therapy and trial entry was stratified for disease activity. Fish oil significantly increased the eicosapentaenoic acid content of rectal mucosa to 3.2% of total fatty acids at six months, compared with 0.63% for patients on olive oil. This was associated with increased synthesis of leukotriene B5, and 53% suppression of leukotriene B4 synthesis by ionophore -stimulated neutrophils. Leukotriene B4 suppression persisted for at least two months after treatment was stopped. Treatment with fish oil resulted in measurable, but only limited clinical benefit. For patients entering the trial in relapse (n=53), there was a significant reduction in corticosteroid requirement after one and two months treatment. There was a trend towards achieving remission (off corticosteroids) faster in the patients on fish oil, although differences were not significant. For patients in remission at trial entry or during the trial (n=69), there was no significant difference in the rate of relapse by log rank analysis. We conclude that fish oil supplementation produces a modest corticosteroid sparing effect in active disease, but there is no benefit in maintenance therapy.

Summary Background : Peristomal infection can sometimes complicate percutaneous endoscopic gastrostomy (PEG) placement. Antibiotic prophylaxis has, in some studies, been shown to reduce the incidence. However, the use of prophylaxis varies widely, possibly because the design and findings of the studies have differed, making their relevance to clinical practice difficult to interpret. Aim : To determine the efficacy of antibiotics, either prophylaxis or concurrent antibiotics at the time of the procedure, in reducing peristomal infection after PEG insertion in the context of a study designed to reflect current practice. Methods : One hundred and forty‐one patients undergoing PEG placement were randomised to group one to receive either a single dose of 750 mg of intravenous cefuroxime (n = 50) or placebo (n = 51) 30 min before PEG insertion. Forty patients who, for various reasons, were already receiving antibiotics were allocated to group two. The peristomal site was evaluated on day 3, 5 and 7 following insertion. Erythema and exudate were scored on a scale from 0 to 4; induration was scored on a scale of 0–3. A maximum combined score of 8 or higher or the presence of pus was criteria for infection. The primary outcome measure was the occurrence of a peristomal wound infection at any time within one week of PEG insertion. Results : Peristomal wound infection was significantly reduced in patients who received antibiotics either as a single dose of cefuroxime [one of 33 (3%)], or in those on antibiotics for prior indications [one of 36 (3%)], compared with placebo [six of 33 (18%)], P = 0.04 and 0.03, respectively. Conclusion : Antibiotics, either prophylaxis or concurrent, reduce the incidence of peristomal wound infection after PEG placement.

1. Gastric damage induced by low‐dose aspirin and the protective effect of enteric‐coating was assessed in healthy volunteers in a double‐blind placebo‐controlled cross‐over trial using Latin square design. Each was administered placebo, plain aspirin 300 mg daily, plain aspirin 600 mg four times daily, enteric‐coated aspirin 300 mg daily, or enteric‐ coated aspirin 600 mg four times daily for 5 days. Gastric damage was assessed endoscopically, and gastric mucosal bleeding measured. 2. Aspirin 300 mg daily and 600 mg four times daily caused significant increases in gastric injury compared with placebo. Gastric mucosal bleeding was significantly more with the high dose, with a trend towards increased gastric erosions, compared with the low dose. 3. Enteric‐coating of aspirin eliminated the injury caused by low dose aspirin and substantially reduced that caused by the higher dose. 4. All dosages and formulations caused similar inhibition of gastric mucosal prostaglandin E2 synthesis. 5. Serum thromboxane levels were suppressed equally with plain and enteric‐coated aspirin. 6. In this short‐term study in healthy volunteers, gastric toxicity from aspirin was largely topical, independent of inhibition of prostaglandin synthesis, and could be virtually eliminated by the use of an enteric‐ coated preparation.

Interleukin 113 in biopsy specimens from inflamed colonic mucosa of patients with active inflammatory bowel disease was studied. Compared with normal colonic mucosal biopsy specimens, a significantly greater amount of interleukin ,13 was present in rectal mucosa before (median (range) 4*3 (2-0-11.8) v 119-2 (30.1-286.8) pg/mg; p<001) and produced during organ culture (39.1 (9.4-106-8) Interleukin 1 has been shown to be a mediator of a number of inflammatory and immunological responses." The precise mechanisms leading to inflammation in inflammatory bowel disease remain to be determined, however, and the mode of action of the therapeutically active drug 5-aminosalicylic acid is not clear. There are good reasons to believe that interleukin may be implicated in the pathogenesis of inflammatory bowel disease.' Its functional properties include T lymphocyte activation,4 enhanced antibody synthesis by B lymphocytes,5 and increased fibroblast proliferation.6 It induces adhesion molecules on endothelial cells which facilitate migration of polymorphonuclear leucocytes and mononuclear cells to sites of inflammation.7 It is also an endogenous pyrogen and induces synthesis of acute phase proteins by hepatocytes.2Enhanced production of interleukin 113 by mononuclear cells isolated from colonic mucosa with active inflammatory bowel disease has been shown.8 In the present study, we investigated whether the therapeutically active drug 5-aminosalicylic acid could inhibit interleukin 113 production by biopsy specimens from inflamed colons, and compared it with sulphapyridine (the therapeutically inactive moiety of sulphasalazine) and dexamethasone, whose effects on interleukin ,13 synthesis by monocytes have previously been characterised.9 We also evaluated the relation of interleukin 13 and thromboxane B2 and studied the effect of 5-aminosalicylic acid on basal synthesis of eicosanoids. Methods PATIENTSTwenty four patients with active ulcerative colitis (14 women, six men; median age 48 5 years (range 20-79)), two with active Crohn's disease (both women, aged 20 and 32 years), and 12 patients with normal colons (five women, seven men; median age 52 5 (range 27-81)) were studied. Biopsy specimens were obtained while these patients were undergoing colonoscopy for clinical reasons. The control group with normal colonic mucosa (confirmed on routine histology) were patients who were undergoing investigations for gastrointestinal symptoms and in whom no abnormality of the gastrointestinal tract was found.Eight patients with inflammatory bowel disease were being treated with sulphasalazine, seven with mesalazine, six with oral prednisolone, four with steroid enemas, and four with azathioprme.

SUMMARYBackground: Opioids change gut motility and secretion, causing delayed intestinal transit and constipation. Endorphins play a role in the constipation troubling some patients with irritable bowel syndrome; hence naloxone, an opioid antagonist, may have a therapeutic role. Aim: To assess the efficacy and safety of an oral formulation of naloxone in irritable bowel syndrome patients with constipation. Methods: A randomized, double-blind, placebo-controlled trial was performed. Patients fulfilling the Rome II criteria for irritable bowel syndrome (constipationpredominant and alternating types) were randomized to receive 8 weeks of treatment with naloxone capsules, 10 mg twice daily, or identical placebo.

Fluticasone propionate is a corticosteroid with the potential for topical treatment of ulcerative colitis because of low systemic bioavailability. The drug was compared with prednisolone in the management of active left sided or total ulcerative colitis. Two hundred and five patients were studied in the multicentre four week double blind study. Prednisolone was given in a dose of 40 mg daily orally, reducing over four weeks to 10 or 20 mg. Fluticasone propionate was given in an oral daily dose of 20 mg. The primary end point was the investigator's overall assessment of response. Patient's assessment, sigmoidoscopic appearance, and histology were also studied. Patients improved more rapidly with prednisolone. Differences between the two groups were significant at two weeks. At four weeks differences were not significant, but there was a trend in favour ofprednisolone. Corticosteroid side effects were minimal in the fluticasone propionate group, and there was minimal suppression of the hypothalamic pituitary adrenal axis. Fluticasone propionate 20 mg daily is not as effective in the treatment of active ulcerative colitis as prednisolone tapering from 40 mg daily to 10 or 20 mg. The complete absence of suppression of the corticoadrenal axis by fluticasone propionate was encouraging, however, and a higher dosage schedule should be assessed. (Gut 1993; 34: 125-128) Corticosteroid drugs are the most effective and widely used treatment for acute relapse ofulcerative colitis. High dosage or prolonged treatment is associated with a range of side effects. Topically active corticosteroids, with reduced systemic bioavailability, should have fewer side effects, and there is evidence that enema preparations of corticosteroid drugs with metabolism in gut wall or liver are effective in distal colitis. [1][2][3]