D. A. Burke

Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility.

A genome-wide association scan in individuals with Crohns disease by the Wellcome Trust Case Control Consortium detected strong association at four novel loci. We tested 37 SNPs from these and other loci for association in an independent case-control sample. We obtained replication for the autophagy-inducing IRGM gene on chromosome 5q33.1 (replication P = 6.6 × 10−4, combined P = 2.1 × 10−10) and for nine other loci, including NKX2-3, PTPN2 and gene deserts on chromosomes 1q and 5p13.

The efficacy of tobramycin in the treatment of ulcerative colitis

This paper reports a double‐blind placebo‐controlled trial of oral tobramycin in acute ulcerative colitis. Eighty‐four patients with an acute relapse of ulcerative colitis were randomized to receive oral tobramycin or placebo for 1 week as an adjunct to steroid therapy. At endpoint, 31 of 42 (74%) in the tobramycin group achieved complete symptomatic remission compared with 18 of 42 (43%) in the placebo group (P= 0.008). The tobramycin group achieved better histological scores (P < 0.05) at endpoint. These findings show that treatment with oral tobramycin improves the short‐term outcome of patients with ulcerative colitis in relapse.

Adhesive Escherichia coli in inflammatory bowel disease and infective diarrhoea.

The clinical features of ulcerative colitis and Crohns disease are similar to those of infections of the bowel, although their cause is uncertain. Many bacteria that cause intestinal diseases adhere to the gut mucosa, and adhesion of pathogenic Escherichia coli is resistant to D-mannose. The adhesive properties of isolates of E coli were assessed by assay of adhesion to buccal epithelial cells with mannose added. The isolates were obtained from patients with inflammatory bowel diseases (50 with a relapse of ulcerative colitis, nine with ulcerative colitis in remission, 13 with Crohns disease, and 11 with infectious diarrhoea not due to E coli) and 22 controls. The median index of adhesion to buccal epithelial cells (the proportion of cells with more than 50 adherent bacteria) for E coli from patients with ulcerative colitis in relapse was significantly higher (43%) than that for controls (5%) and patients with infectious diarrhoea (14%). The index was not significantly different among isolates from patients with ulcerative colitis in relapse, Crohns disease (53%), and ulcerative colitis in remission (30%). If an index of adhesion of greater than 25% is taken as indicating an adhesive strain 86% of isolates of E coli from patients with inflammatory bowel disease were adhesive compared with 27% from patients with infective diarrhoea and none from controls. The adhesive properties of the isolates from patients with inflammatory bowel disease were similar to those of pathogenic intestinal E coli, raising the possibility that they may have a role in the pathogenesis of the condition; the smaller proportion of adhesive isolates in patients with infective diarrhoea due to other bacteria suggests that the organism may be of primary importance rather than arising secondarily.

The role of azathioprine in the management of ulcerative colitis.

The use of azathioprine in ulcerative colitis is unclear. The authors present the details and outcome of 47 patients who received azathioprine for either a) severe, resistant disease otherwise requiring surgery (28 patients) or b) patients with steroid dependence who have been followed up for at least 12 months (19 patients). Duration of treatment ranged from one week to 66 months (median, 12 months). Of the patients in Group I, 13 (46 percent) achieved remission, 11 of whom had not relapsed during a median follow-up of 22 months (range, 12 to 58 months), and 15 underwent surgery one week to 12 months (median, five weeks) after commencing azathioprine. In Group II, steroids were withdrawn or reduced in 12 (63 percent) patients and three patients required colectomy. Side effects necessitating withdrawal of azathioprine occurred in 12 patients (hematologic effects, 6 patients; gastrointestinal effects, 4 patients; other effects, 2 patients). Two patients required a reduced dose of azathioprine because of leukopenia. The authors conclude that azathioprine is a valuable therapeutic option in selected patients with ulcerative colitis.

Oral tobramycin in ulcerative colitis: effect on maintenance of remission

Oral tobramycin for 7 days has been shown to be of benefit as an adjunct to conventional medication in acute ulcerative colitis. Eighty‐one patients (40 who had received tobramycin; 41 placebo) who had been enrolled in a double‐blind placebo‐controlled trial of this drug in acute disease were subsequently followed to determine whether this short‐term benefit persisted. Relapse was defined as a liquid stool frequency of three times daily with rectal bleeding. Results were analysed by the log‐rank test on Kaplan‐Meier survival curves. Treatment failure was defined as a lack of response by the end of the acute trial period, or subsequent relapse. In a second analysis, only those entering remission at the end of the acute trial were considered, and followed to relapse. Although at the start of the follow‐up period significantly fewer patients in the tobramycin group had failed (failed: tobramycin 9, placebo 24; not failed tobramycin 31; placebo 17;P= 0.001), the failure‐free survival curves subsequently converged and did not differ significantly. After 1 and 2 years, the failure‐free survival rates were 40% (S.E. = 7.8%) and 20% (S.E. = 6.3%) for the tobramycin group and 24% (S.E. = 6.7%) and 12% (S.E. = 5.1%) for the placebo group. When only those entering remission were considered, there was no significant difference in the relapse rates in the two groups. Benefit from tobramycin is therefore short‐lived and may reflect short‐term changes in the faecal flora.

Oral antioxidant supplementation for fatigue associated with primary biliary cirrhosis: results of a multicentre, randomized, placebo-controlled, cross-over trial

Background : We have previously reported, in an uncontrolled trial, an improvement in fatigue scores in patients with primary biliary cirrhosis given oral antioxidant supplementation. We now present data from a controlled trial.

Fatal pulmonary fibrosis occurring during treatment with cyclophosphamide.

S flexneri has the smallest infecting dose of enteropathogenic bacteria-namely, about 200 viable cells for healthy volunteers-so that infections in laboratory workers are not uncommon.2 Interestingly, laboratory-acquired infections of all kinds have in general occurred most often in trained bench workers in diagnostic services, and spills and sprays have equalled hypodermic needles as the commonest mode.1 In this case gargling with copious water followed by thorough washing of the face and hands with soap and water might have been more effective than the brief exposures to antiseptics. The State Health Commission recommends a phenolic disinfectant for laboratory fixtures but offers no guidance on measures for people who become contaminated.3

A method of enhancing verocytotoxin production by Escherichia coli

The number of verocytotoxin producing Escherichia coli (VTEC) present in the faeces during an infection may be very low, making their detection difficult. We report a method for enhancing toxin production by VTEC using mitomycin C as an inducing agent with the aim of improving the detection of VTEC. In pure culture, mitomycin C enhanced toxin production up to 100-fold. When applied to mixed faecal culture, toxin could be detected in mitomycin C treated samples when standard cultures were negative and when substantially fewer verocytotoxin-producing bacteria were present. Use of this method may aid in the detection of VTEC and is appropriate for use in the routine diagnostic laboratory.

Ulcerative colitis: prolonged remission following azathioprine-induced pancytopenia.

The patient reported here has had prolonged remission following a chronic relapsing course of ulcerative colitis requiring frequent use of systemic steroids. All inflammatory bowel disease symptoms resolved after treatment with azathioprine, which was associated with the development of pancytopenia. The patient remains in clinical, sigmoidoscopic, and histological remission 56 months after receiving azathioprine.

Oral bowel lavage preparation for colonoscopy.

Colonoscopy is a commonly performed diagnostic and therapeutic procedure in most general hospitals, which requires effective bowel preparation to be worthwhile. We report the effect of replacing a diet, laxative and bowel washout preparation with oral bowel lavage using a balanced electrolyte formulation, in our unit. The preparation was acceptable to patients, medical and nursing staff, generally preferred to previous preparations by those who had experienced them, allowed a more complete colonoscopy with an excellent quality of view, and was less expensive in nursing time. We regard oral bowel lavage as currently the method of choice for bowel preparation prior to colonoscopy in the majority of patients.