Long-term follow-up of coeliac disease--what do coeliac patients want?

BACKGROUND: Coeliac disease affects up to 1% of the population and the British Society of Gastroenterology recommends long-term follow-up of these patients, although the absolute risk of complications is small. AIM: To determine what proportion of patients with coeliac disease remain under specialist follow-up and to examine patients' perspectives on the long-term management of coeliac disease. METHODS: A questionnaire was sent to 183 patients who had a duodenal biopsy between July 1994 and July 2004 which was consistent with coeliac disease. RESULTS: A total of 126 (69%) patients returned their questionnaire. Patients had on average been diagnosed with coeliac disease 5.4 years earlier. Eighty-eight percentage were trying to follow a strict gluten-free diet. Sixty-two percentage of patients were under regular follow-up although this varied between hospital clinic (doctor/dietitian, 92%) and General Practitioner (8%). Most patients found at least one aspect of the hospital out-patient clinic very useful. The preferred method of coeliac disease follow-up was to see a dietitian with a doctor being available (P < 0.05 vs. all other options). CONCLUSIONS: Respondents to this study showed great variation in follow-up of their coeliac disease -38% were under no active follow-up. Patients would prefer to see a dietitian for long-term follow-up.

Effects of Helicobacter pylori on the cadherin-catenin complex.

BACKGROUND: The cadherin-catenin complex is the key component of the adherens junction in epithelial cells, and changes in this complex are implicated in gastric adenocarcinoma. Germline mutations in E-cadherin have been described in diffuse-type gastric adenocarcinoma. Helicobacter pylori infection is the first stage in gastric carcinogenesis. AIMS: To determine whether H pylori was associated with changes in the complex, and whether this was affected by virulence of the strain. METHODS: Epithelial cell lines were cultured with H pylori using the wild-type pathogenic and non-pathogenic strains and CagE null and VacA null isogenic mutants. Gastric biopsy specimens at endoscopy were obtained from patients with (n = 17) and without (n = 15) H pylori infection, and E-cadherin and beta-catenin expression was assessed by immunohistochemistry. H pylori was typed by polymerase chain reaction from these patients for CagE and VacA. RESULTS: In vitro studies showed that coculture with a pathogenic strain of H pylori led to disruption of epithelial junctional beta-catenin expression, but without evidence of nuclear translocation or signalling. This effect was independent of a functional Cag pathogenicity island and vacuolating activity, but dependent on live bacteria. No marked differences in beta-catenin or E-cadherin expression were seen in gastric biopsy specimens in patients with and without H pylori infection. CONCLUSION: Acute H pylori infection disrupts junctional beta-catenin in vitro, but chronic infection by H pylori has no effect on E-cadherin and beta-catenin expression, as seen in gastric biopsy specimens at the initial gastritis stage of the proposed Correa pathway of gastric carcinogenesis. A later effect at the later stages of atrophy or intestinal metaplasia cannot be ruled out.

Review article: does the use of immunosuppressive therapy in inflammatory bowel disease increase the risk of developing lymphoma?

Recent case reports have raised concerns regarding the risks of non-Hodgkin's lymphoma in patients with inflammatory bowel disease treated with immunosuppressive agents. This evidence-based review examines this issue from data derived from the use of immunosuppression in other conditions (and inflammatory bowel disease). We conclude that, in transplant (cardiac and renal) recipients, immunosuppression increases the risk of non-Hodgkin's lymphoma. For non-transplant patients (with psoriasis and rheumatoid arthritis), debate remains as to whether the observed increase in the incidence of non-Hodgkin's lymphoma is due to drug or disease. For inflammatory bowel disease per se, population studies show no significant increase in the risk of non-Hodgkin's lymphoma, with a relative risk of 1.3 (95% confidence interval, 0.9-1.7) compared to expected rates, and several studies of immuno- suppression in inflammatory bowel disease do not appear to confirm a significant rate of lymphoma incidence. Reported cases of lymphoma from single centres should be viewed with caution as evidence of increased risk. If any association exists, it is likely to be of minimal clinical significance compared to the established and more frequent risks of myelosuppression and infection, and is unlikely to outweigh the benefit of immunosuppression in inflammatory bowel disease.

How effective are the usual treatments for ulcerative colitis?

BACKGROUND: Details of the efficacy of the drugs used in ulcerative colitis are not readily available. METHODS: We have reviewed all placebo-controlled trials of the commonly used drugs for both induction and maintenance of remission to determine the efficacy and to calculate the numbers needed to treat (NNTs) to achieve a specified benefit for each drug. RESULTS: The drug response rates and the NNTs (with 95% CI) are tabulated for each drug. CONCLUSION: Corticosteroids give a remission rate of 68% in mild or moderate disease and an NNT for remission of 2 (95% CI 1.4-5) in mild disease. Intravenous hydrocortisone gives a remission rate of 60-73%. Aminosalicylates are relatively ineffective in inducing remission with an NNT of 10 (95% CI 7-21) improving to 8 (95% CI 5-20) if the dose > or = 3 g daily. They are better at maintenance (NNT = 6; 95% CI 4-8). Intravenous ciclosporin is very effective in achieving remission in severe colitis with an NNT of 1.2 (95% CI 1-2.5). Although there is fairly good evidence that azathioprine is effective in maintaining remission and is used widely, there are no suitable placebo-controlled trials to calculate the NNT.

How effective are the usual treatments for Crohn's disease?

BACKGROUND: Details of the efficacy of the various drugs used in Crohn's disease are not readily available. METHODS: We have reviewed all placebo controlled trials of the commonly used drugs in Crohn's disease for both the induction and maintenance of remission to determine the efficacy and to calculate the numbers needed to treat (NNTs) to achieve a specified benefit for each drug. RESULTS: Both the drug response rates and the NNTs (with 95% confidence intervals) are tabulated for each drug. CONCLUSION: Prednisolone/prednisone is the most effective drug to achieve remission with a remission rate of 60% and an NNT for remission of 3 (95% confidence interval: 2-6). Aminosalicylates are only moderately effective in achieving remission with an overall NNT of 10 (95% confidence interval: 6-75), but more effective in high-dose (e.g. NNT for Pentasa 4 g daily = 4; 95% confidence interval: 2.6-9), and less effective in maintaining remission with an NNT of 14 (95% confidence interval: 9-29). Both azathioprine and infliximab are associated with remission induction and maintenance rates of 40-66% and NNTs of 3-5. Methotrexate intramuscularly has a remission induction rate of 39% and an NNT of 5 (95% confidence interval: 3-25).

Familial colonic varices--a cause of "polyposis" on barium enema.

A 61-year-old woman with diarrhoea had multiple filling defects on a barium enema and was assumed to have multiple colonic polyps. However, colonoscopy showed colonic varices and relatively few true polyps. She bled significantly after polypectomy of a tubular adenoma. There was no evidence to support a diagnosis of portal hypertension or liver disease. A case report of her father's idiopathic colonic varices has previously been reported in this journal in 1985, and we update his subsequent progress and discuss other reports of this rare condition.

Helicobacter pylori upregulates matrilysin (MMP-7) in epithelial cells in vivo and in vitro in a Cag dependent manner.

BACKGROUND AND AIMS: Matrix metalloproteinase-7 (MMP-7) is important in normal and pathological remodelling of epithelial-matrix interactions, and is upregulated in gastric cancer. Helicobacter pylori infection is the first stage in gastric carcinogenesis, and therefore our aim was to determine if H pylori upregulated gastric MMP-7 expression and if this was affected by strain virulence. METHODS: We took gastric biopsy specimens at endoscopy from H pylori infected (n = 17) and uninfected (n = 18) patients and assessed MMP-7 expression by ELISA, real time polymerase chain reaction (PCR), and immunohistochemistry (concentrating on epithelial cells in the proliferative zone). We PCR typed H pylori for cagE and vacA. We performed H pylori/cell line coculture studies with wild-type pathogenic and non-pathogenic H pylori strains and with CagE(-) and VacA(-) isogenic mutants. RESULTS: Gastric biopsy specimens from H pylori+ patients expressed higher levels of MMP-7 at the protein and mRNA levels in the antrum and corpus (for example, by ELISA: H pylori+ 0.182 OD units vH pylori- 0.059; p = 0.009 antrum). Epithelial cells from H pylori+ patients stained more intensely for MMP-7 than those from uninfected patients, including in the proliferative zone containing pluripotent cells (p<0.03 antrum, p<0.04 body). Upregulation of MMP-7 in epithelial cells was confirmed at the protein and mRNA levels by H pylori/cell line coculture. These experiments also showed that MMP-7 upregulation was dependent on an intact H pyloricag pathogenicity island but not on the vacuolating cytotoxin. CONCLUSION: We speculate that increased expression of MMP-7 in H pylori gastritis may contribute to gastric carcinogenesis.

Gastrointestinal safety of AZD3582, a cyclooxygenase inhibiting nitric oxide donator: proof of concept study in humans.

BACKGROUND: Cyclooxygenase inhibiting nitric oxide donators (CINODs) are a new class of anti-inflammatory and analgesic drugs that may minimise gastrointestinal toxicity compared with standard non-steroidal anti-inflammatory drugs (NSAIDs) by virtue of nitric oxide donation. METHODS: A proof of concept study of the gastrointestinal safety of AZD3582, the first CINOD available for human testing, was conducted. Thirty one subjects were randomised to receive placebo, naproxen 500 mg twice daily, or its nitroxybutyl derivative AZD3582 in an equimolar dose (750 mg twice daily) for 12 days in a double blind three period crossover volunteer study. At the start and end of each dosing period, gastroduodenal injury was assessed by endoscopy and small bowel permeability by differential urinary excretion of lactulose and L-rhamnose. Pharmacokinetic profiles were assessed at steady state. RESULTS: On naproxen, the mean total number of gastroduodenal erosions was 11.5 (and one subject developed an acute ulcer) versus 4.1 on AZD3582 (p<0.0001). More than half of the subjects had no erosions on AZD3582. Differences were seen for both the stomach and duodenum. Naproxen increased intestinal permeability (lactulose:L-rhamnose ratio 0.030 before v 0.040 after treatment) whereas AZD3582 (0.029 before, 0.029 after; p=0.006 v naproxen) and placebo (0.030 before, 0.028 after; p<0.001 v naproxen) did not. The steady state bioavailability of naproxen metabolised from AZD3582 was 95% (95% confidence interval 87-101%) of that after naproxen administration. CONCLUSIONS: This human study supports animal data showing reduced gastrointestinal toxicity with the CINOD AZD3582. The potential combination of effective pain relief and gastrointestinal protection offered by AZD3582 warrants further evaluation in human clinical studies.