Genetic refinement and physical mapping of a chromosome 16q candidate region for inflammatory bowel disease.

Crohn's disease (CD) is a complex genetic disorder for which a susceptibility gene, IBD1, has been mapped within the pericentromeric region of chromosome 16. In order to refine the location of IBD1, 77 multiplex CD families were genotyped for 26 microsatellite markers evenly spaced by approximately 1 cM. Nonparametric linkage analyses exhibited a maximum NPL score of 3.49 (P=2.37x10(-4)) in a region centred by markers D16S3136, D16S3117 and D16S770. Simulation studies showed that the probability for IBD1 to be located in a 5 cM region around these markers was 70%. A 2.5 Mb YAC and BAC contig map spanning this genetic region on chromosome band 16q12 was built. TDT analyses demonstrated suggestive association between the 207 bp allele of D16S3136 (P<0.05) and a new biallellic marker hb27g11f-end (P=0.01). These markers were located in the hb27g11 and hb87b10 BAC clones from the contig. Taken together, the present results provide a crucial preliminary step before an exhaustive linkage disequilibrium mapping of putatively transcribed regions to identify IBD1.

Clustering of Crohn's disease within affected sibships.

Crohn's disease (CD) is a complex genetic disorder for which aetiology is unknown. Recently, genetic factors for susceptibility have been described. Several genetic loci have been mapped and partially explain the familial aggregations of the disease. However, environmental factors may also contribute to these aggregations. We considered that if the role of non-genetic factors was negligible, CD patients would be randomly distributed in sibships with multiple affected siblings. On the other hand if there was a significant environmental contribution, the siblings would be affected non-randomly over exposure status. In order to test this hypothesis, we studied 102 sibships with two or more affected siblings. A statistical test, named Cluster of Affected Sibling Test or CAST, was developed, based on the exact calculation of the probability of observing a given number of clusters of affected siblings in multiplex families. The null hypothesis of a random distribution of affected siblings was rejected (P=0.005). The observed excess of affected sibling clusters indicates that birth order influences the disease status. Considering that an adjacent order of birth is a global estimate of environmental sharing, this observation strongly suggests that environmental factors contribute to the observed familial aggregations of the disease. This observation provides evidence that familial CD is a relevant tool for further studies of environmental factors and gene-environment interaction. More generally, the CAST statistics may be widely applicable to estimate the involvement of environmental factors in the aetiology of other binary traits which may be observed in multiple members of the same sibship.

Immunosuppressors for inflammatory bowel disease: how long is long enough?

Immunosuppressors used in inflammatory bowel disease (IBD) are useful in refractory, chronic, active, steroid-dependent, or steroid-resistant IBD, but do not provide a permanent cure for IBD, their effect being only temporary. Only azathioprine and methotrexate are currently prescribed in the long term for IBD. The question of how long immunosuppressors should be given once remission has been induced and steroids discontinued has not yet been answered.

A randomized, double-blind, placebo-controlled trial of olsalazine for active Crohn's disease.

SUMMARY: : Olsalazine, consisting of two salicylate radicals linked by an azo-bond, is effective in the treatment of active ulcerative colitis. To test its effect in patients with mild to moderate attacks of Crohn's disease, the International Organization for the Study of Inflammatory Bowel Disease (IOIBD) designed a multicentre, randomised, double-blind, placebo-controlled study. Ninety-one patients from four centres were randomised to receive either olsalazine, 1 g b.i.d., or matching placebo tablets. Twenty-six patients had ileal disease; 43, ileocolonic; and 22, colonic. Thirty-five of 46 patients taking olsalazine and 24 of 45 patients taking placebo were withdrawn before the end of the 4-month study. Diarrhoea was the most common reason for withdrawal from the olsalazine group, accounting for 22% of the patients, as compared with 4% in the placebo group. No other side effects were reported. There was no difference in the remission rate or withdrawal rate for active disease in the two groups. However, when an intent-to-treat analysis was performed, only eight of the 46 (17%) olsalazine-treated patients were considered to have entered remission or improved their symptoms compared with 22 of the 45 (49%) placebo-treated patients (p < 0.03). This study was unable to show that patients with mild to moderate attacks of Crohn's disease were significantly improved by treatment with olsalazine at a dose of 1 g daily. However, the potential benefit of a higher dose cannot be excluded.

An open-label study of thalidomide for maintenance therapy in responders to infliximab in chronically active and fistulizing refractory Crohn's disease.

BACKGROUND: Infliximab, a chimeric monoclonal antibody to tumour necrosis factor-alpha, is a new potent therapy for active Crohn's disease, but induces short-lived improvements. AIM: To evaluate the efficacy of thalidomide, a drug with anti-tumour necrosis factor-alpha activity, for the maintenance of infliximab-induced response in refractory Crohn's disease. METHODS: Fifteen patients with severe, refractory disease (10 females, five males; mean age, 40 years; eight with luminal disease, two with fistulizing disease and five with both luminal and fistulizing disease) were started on thalidomide (100 mg daily), 29 +/- 10 days after they had responded to infliximab (5 mg/kg infusions). RESULTS: The median follow-up period was 238 days (range, 10-458 days) from the initiation of thalidomide and 265 days (range, 10-537 days) from the last infliximab infusion. The median Crohn's disease activity indices were 322 (range, 170-525), 119 (range, 24-503) and 35 (range, -60-360) before infliximab, at the initiation of thalidomide and at the end of follow-up, respectively. Remission rates on thalidomide were 92%, 83% and 83% at 3, 6 and 12 months, respectively, after the last infliximab infusion (Kaplan-Meier). Four patients (two in remission) stopped thalidomide for suspected adverse effects. Side-effects (drowsiness, rash and peripheral neuropathy) were mild and mostly transient. CONCLUSIONS: Thalidomide appears to be an effective and relatively safe drug to maintain response to infliximab in chronically active and fistulizing refractory Crohn's disease.

Methotrexate for the treatment of refractory Crohn's disease.

BACKGROUND: Previous studies suggested that methotrexate has beneficial effects in patients with Crohn's disease. We report our experience with this agent in patients with chronic active Crohn's disease who previously failed to improve with conventional treatment, including azathioprine in most cases. METHODS: Between June 1988 and June 1992, 39 patients with refractory Crohn's disease were treated with methotrexate. In patients with active disease, clinical remission was defined by a Harvey-Bradshaw index of less than 4. For patients also taking corticosteroids, the dates of remission and complete steroid withdrawal were recorded. For patients who achieved clinical remission, and those in clinical remission when methotrexate was started, the relapse rate on methotrexate therapy was noted. RESULTS: In the 37 patients with active disease at methotrexate initiation, the probability of remission was 72% at 3 months. The probability of remission and steroid withdrawal was 42% at 12 months. In patients on clinical remission, the probability of relapse on methotrexate was 58% at 12 months. Twenty-two patients experienced side-effects, but these only warranted methotrexate discontinuation in four cases. CONCLUSIONS: Methotrexate appears effective in most patients with refractory Crohn's disease and its short-term toxicity is acceptable, but the long-term benefit seems more limited.

Infliximab for refractory ulcerative colitis or indeterminate colitis: an open-label multicentre study.

BACKGROUND: The efficacy of infliximab in ulcerative colitis (UC) and indeterminate colitis has been poorly assessed and preliminary results are conflicting. METHODS: The records of 30 patients treated with infliximab for ulcerative colitis (n=19) or indeterminate colitis (n=11) were reviewed. Infliximab was given because of steroid resistance (n=18), dependence (n=5) or intolerance (n=7); five patients had failed on cyclosporin; 19 patients had a severe flare-up. RESULTS: Median duration of follow-up was 10 months. In 28 patients with active disease, the response rate was 75% at day 7, with 43% having a complete remission, and 50% at month 1, with 32% having a complete remission. Among the 22 responders, the probability of relapse was 73% at month 6. The probability of complete remission without steroids, taking into account the re-treatment for relapse (n=11), was 57% (95% confidence interval (CI): 45% to 69%) at month 6. The probability of colectomy was 33% (95% CI: 23% to 43%) at month 12. In indeterminate colitis, response rate was only 50% at day 7 and 30% at month 1. Concomitant use of antimetabolite agents was associated with better results. CONCLUSIONS: Infliximab was able to induce a rapid response in some patients with UC or indeterminate colitis refractory to conventional treatment. Long-term results were less favourable, with frequent relapses, and about one-third of the patients required a colectomy.

Hydrostatic balloon dilatation of Crohn's strictures.

AIM: To evaluate the safety and long-term efficacy of per-endoscopic hydrostatic balloon dilatation in a retrospective series of patients with Crohn's disease. METHODS: Thirty-eight patients had balloon dilatation for intestinal symptomatic strictures which were located as follows: ileo-colonic (26) or colocolic (2) anastomosis, colon (4), ileum (3), proximal jejunum (1) and ileo-caecal valve (5); three patients had two strictures accessible to dilatation. The mean length of the strictures was 2.1 cm (s.d., 0.3 cm). RESULTS: Thirty-two of the 38 patients were successfully dilated and followed for a median of 22.8 months (0.2-103 months) until surgery or last news. The probabilities of obstructive symptom recurrence were 36% at 1 year and 60% at 5 years. Twelve patients had a second dilatation, and three a third. The probabilities of surgery for stricture were 26% at 1 year and 43% at 5 years. Results were not influenced by age, sex, activity of the disease, passage of the stricture by the colonoscope or concomitant medical therapies. Complications occurred in 9.4% of the 53 dilatation sessions, with only one perforation. CONCLUSIONS: Hydrostatic balloon dilatation is effective for Crohn's symptomatic strictures, and can avoid or postpone surgery, with an acceptable rate of complications.

Comparison of budesonide and 5-aminosalicylic acid enemas in active distal ulcerative colitis.

BACKGROUND: Budesonide is a new corticosteroid with high topical anti-inflammatory activity but little systemic effect. The aim of the present study was to compare the efficacy and safety of budesonide enema (2 mg/100 mL) and 5-ASA enema (mesalazine 1 g/100 mL) given for 4 weeks in the treatment of active distal ulcerative colitis and proctitis. METHODS: Ninety-seven patients were studied in a multicentre single-blind randomized group-comparative trial. The primary efficacy variables were endoscopy and histopathology scores obtained at 0, 2 and 4 weeks. Clinical symptoms were the secondary efficacy variables. Haematology, chemistry and adverse events were the safety variables. RESULTS: Budesonide and 5-ASA enemas both resulted in a significant improvement in endoscopy and histopathology scores but no difference could be demonstrated between the two treatment groups. There was also a significant improvement of symptoms (number of bowel movements per day, quality of stools, presence of blood and mucus, and state of well-being) within both groups but no difference between the two treatment groups. The clinical remission rate at 4 weeks was, however, 38% for patients treated with budesonide enema but 60% for those treated with 5-ASA enema (P = 0.03). No adverse events attributed to the study drugs were recorded in either of the groups. CONCLUSIONS: Budesonide enema 2 mg/100 mL appears to be as efficient and well-tolerated as 5-ASA enema in the treatment of active distal ulcerative colitis and proctitis.

Treatment of severe Crohn's disease with anti-CD4 monoclonal antibody.

BACKGROUND: Monoclonal CD4 antibodies have been proposed as a new immunosuppressant drug in the treatment of inflammatory bowel disease. We report our experience of treatment with a monoclonal anti-CD4 (B-F5) antibody in severe refractory Crohn's disease. METHODS: Twelve patients with severe refractory Crohn's disease were treated in an open clinical trial. B-F5 was given intravenously at a dose of 0.5 mg. day/kg for 7 consecutive days (patients 1-8). For patients 9-12, B-F5 was given at a dose of 0.5 mg. day/kg on the first day (day 0) and of 1 mg.day/kg on days 1-6. Follow-up examinations were carried out at days 8, 15, 22 and 30. Endoscopic evaluation was performed on days 0 and 30 in eight of 12 patients. RESULTS: Immediately after the first infusion, one patient had dyspnoea and tachycardia requiring cessation of the treatment. Among the 11 patients who received the complete course of treatment, two had prolonged clinical improvement and two had partial clinical improvement. Significant endoscopic improvement was observed in only one patient. No sustained depletion of CD4+ cells could be observed. CONCLUSION: In this uncontrolled open trial, monoclonal anti-CD4 B-F5 antibody was not successful in severe Crohn's disease.

Drug therapy for ulcerative colitis during pregnancy.

Women with ulcerative colitis (UC) are usually young and thus likely to undergo pregnancy. They should be advised to conceive when the disease is quiescent. Steroids and salicylates may be used normally during pregnancy, possibly without exceeding a dose of 2g/day for mesalazine. Azathioprine can be maintained if its indication is clear cut. Cyclosporin seems to be without additional risk in the pregnant woman, its use being limited to acute steroid-refractory disease, as an alternative to surgery.

Azathioprine for prevention of postoperative recurrence in Crohn's disease: a retrospective study.

BACKGROUND: The efficacy of azathioprine (AZA) in chronically active Crohn's disease (CD) is well established. Whether this drug is also useful to prevent recurrences after surgery is unknown. We report here our experience of AZA in this therapeutic goal. METHODS: Between 1987 and 1996, 38 patients with CD were treated with AZA to prevent postoperative recurrence. Twenty-three of these had undergone a curative resection with removal of all previously involved parts of the gut. In the other 15 patients, resection was limited to the parts of the gut macroscopically abnormal at the time of surgery; those parts that were previously involved but normal at this time were conserved. The operative procedures were ileocolonic resection (n = 18), subtotal colectomy with ileorectal anastomosis (n = 12), coloproctectomy with ileo-anal anastomosis (n = 4) or ileostomy (n = 2), ileal resection (n = 1) and segmental colectomy (n = 1). Twelve patients had been treated previously with AZA before surgery; in 26 patients, AZA was started within the 2 months following surgery. RESULTS: The median duration of postoperative follow-up was 29 months. Probabilities of clinical recurrence according to the Kaplan-Meier method were 9, 16 and 28% at 1, 2 and 3 years, respectively. For the 25 patients who had a colonoscopy or a small bowel barium X-ray during the follow-up, probabilities of anatomical recurrence were 16, 36 and 59% at 1, 2 and 3 years, respectively. The probability of anatomical recurrence was significantly higher in patients who had segments of the gut previously involved but not removed because they were macroscopically normal at the time of surgery. CONCLUSION: In patients treated with AZA, the rate of postoperative endoscopic recurrence was lower than that previously reported in untreated patients. Our results suggest that AZA should be evaluated prospectively for prevention of postoperative CD recurrence, at least in high-risk patients.

Placebo-controlled clinical trial of mesalazine in the prevention of early endoscopic recurrences after resection for Crohn's disease. Groupe d'Etudes Thérapeutiques des Affections Inflammatoires Digestives (GETAID).

OBJECTIVE: Endoscopic postoperative recurrences occur early after 'curative' surgery for Crohn's disease. Pentasa has been shown to be effective in the maintenance treatment of quiescent Crohn's disease. The aim of this study was to test the efficacy of a 12-week oral intake of Claversal in the prevention of endoscopic recurrences after 'curative' resection for ileal, colonic or ileocolonic Crohn's disease. We conducted a multicentre double-blind controlled trial comparing Claversal (1g tid) with placebo, starting within 15 days after surgery. The macroscopic normality of the two anastomotic segments was assessed at surgery. Patients were clinically and biologically evaluated twice (6-week interval), and colonoscopy was performed at 12 weeks. Endoscopic relapse was defined by any anastomotic ulcerations or stenosis and staged according to a four-grade score. RESULTS: Between May 1989 and May 1991 12 centres included 126 patients, 70 women and 56 men, aged 33 +/- 12 years (range 16-70) in the study. Disease locations were ileal, colonic and ileocolonic in 45, 6 and 49%, respectively. Claversal and placebo groups were similar at inclusion, except for ESR (37 +/- 26 vs. 27 +/- 23 mm/h in the Claversal and placebo groups, respectively; P < 0.05). Nine patients were withdrawn from the study. Adverse reactions occurred only in six patients. Five patients were excluded for protocol violation. Finally, 106 patients could be evaluated at 12 weeks (55 Claversal and 51 placebo). An endoscopic relapse was observed in 50% and 63% of the Claversal and placebo groups, respectively (P = 0.16), with a similar grade distribution. Claversal was well tolerated. CONCLUSIONS: Our study confirms that a large proportion of endoscopic recurrences occur within 3 months of resection in Crohn's disease. There was a slight trend towards greater efficacy of Claversal; it could be worthwhile trying higher dosages and/or 5-ASA compounds with different intestinal release profiles.

Corticosteroids for maintaining remission of Crohn's disease.

OBJECTIVES: To evaluate the effectiveness and safety of conventional systemic corticosteroid therapy in maintaining clinical remission in Crohn's disease. SEARCH STRATEGY: A computer-assisted search of the on-line bibliographic database MEDLINE of studies published in English, French, Spanish, Italian and German between 1966 and February, 2001. Manual searches of the reference lists from the potentially relevant studies were performed in order to identify additional studies that may have been missed using the computer-assisted search strategy. Proceedings from major gastrointestinal meetings were also manually searched from 1985 to 2000 in order to identify unpublished studies. The Cochrane Controlled Trials Register and the Inflammatory Bowel Disease Review Group Trials Register were also searched. SELECTION CRITERIA: Randomized double-blind placebo-controlled trials involving patients of any age with Crohn's disease in clinical remission as defined by a CDAI < 150 or by the presence of no symptoms or only mild symptoms at the time of entry into the trial. The experimental treatment consisted of oral conventional corticosteroid therapy (excluding budesonide, fluticasone, etc). Clinical disease relapse was used as the outcome measure of interest. DATA COLLECTION AND ANALYSIS: Eligible studies were selected by 4 reviewers and data were extracted onto standardized data extraction forms. Disagreements in eligibility or data extraction were resolved by consensus. Data were converted into individual 2x2 tables for each study. The presence of significant heterogeneity among studies was tested using the chi-square test. The 2x2 tables were synthesized into a summary test statistic using the pooled odds ratio and 95% confidence intervals as described by Cochran and Mantel and Haenszel (the 'odds ratio' in MetaView). A fixed effects model was used for the pooling of data. MAIN RESULTS: Four studies were initially judged as being eligible for inclusion. After obtaining additional information on one of the studies it was excluded because it was not double-blind. The total number of subjects included in the analysis at the time points of 6, 12 and 24 months were 142, 131 and 95 for the corticosteroid group and 161, 138 and 87 for the control group. The odds ratios for relapse on active treatment and the corresponding 95% confidence intervals were 0.71 (0.39, 1.31), 0.82 (0.47, 1.43) and 0.72 (0.38, 1.35) at 6, 12 and 24 months. REVIEWER'S CONCLUSIONS: The use of conventional systemic corticosteroids in patients with clinically quiescent Crohn's disease does not appear to reduce the risk of relapse over a 24 month period of follow-up. This review updates the existing review of corticosteroids for maintaining remission of Crohn's disease which was published in the Cochrane Library (Issue 2, 2001).

Corticosteroids for maintaining remission of Crohn's disease.

OBJECTIVES: To evaluate the effectiveness and safety of conventional systemic corticosteroid therapy in maintaining clinical remission in Crohn's disease. SEARCH STRATEGY: A computer-assisted search of the on-line bibliographic database MEDLINE of studies published in English, French, Spanish, Italian and German between 1966 and May, 1998. Manual searches of the reference lists from the potentially relevant studies were performed in order to identify additional studies that may have been missed using the computer-assisted search strategy. Proceedings from major gastrointestinal meetings were also manually searched from 1985 to 1997 in order to identify unpublished studies. The Cochrane Controlled Trials Register and the Inflammatory Bowel Disease Review Group Trials Register were also searched. SELECTION CRITERIA: Randomized double-blind placebo-controlled trials involving patients of any age with Crohn's disease in clinical remission as defined by a CDAI < 150 or by the presence of no symptoms or only mild symptoms at the time of entry into the trial. The experimental treatment consisted of oral conventional corticosteroid therapy (excluding budesonide, fluticasone, etc). Clinical disease relapse was used as the outcome measure of interest. DATA COLLECTION AND ANALYSIS: Eligible studies were selected by 4 reviewers and data were extracted onto standardized data extraction forms. Disagreements in eligibility or data extraction were resolved by consensus. Data were converted into individual 2x2 tables for each study. The presence of significant heterogeneity among studies was tested using the chi-square test. The 2x2 tables were synthesized into a summary test statistic using the pooled odds ratio and 95% confidence intervals as described by Cochran and Mantel and Haenszel (the 'odds ratio' in MetaView). A fixed effects model was used for the pooling of data. MAIN RESULTS: Four studies were initially judged as being eligible for inclusion. After obtaining additional information on one of the studies it was excluded because it was not double-blind. The total number of subjects included in the analysis at the time points of 6, 12 and 24 months were 142, 131 and 95 for the corticosteroid group and 161, 138 and 87 for the control group. The odds ratios for relapse on active treatment and the corresponding 95% confidence intervals were 0.71 (0.39, 1.31), 0.82 (0.47, 1.43) and 0.72 (0.38, 1.35) at 6, 12 and 24 months. The numbers needed to treat with corticosteroids to prevent one additional relapse were 24, 35, 15 respectively. REVIEWER'S CONCLUSIONS: The use of conventional systemic corticosteroids in patients with clinically quiescent Crohn's disease does not appear to reduce the risk of relapse over a 24 month period of follow-up.

Azathioprine or 6-mercaptopurine for inducing remission of Crohn's disease.

OBJECTIVES: To determine the effectiveness of azathioprine and 6-mercaptopurine in inducing remission of active Crohn's disease. SEARCH STRATEGY: Studies were selected using the MEDLINE data base (1966 - December 1997), abstracts from major gastrointestinal meetings and references from published articles and reviews. The Cochrane Controlled Trials Register and the Inflammatory Bowel Disease Review Group Trials Register was also searched. SELECTION CRITERIA: Eight randomized placebo controlled trials of azathioprine and 6-mercaptopurine therapy in adult patients were identified: five dealt with active disease and three had multiple therapeutic arms. DATA COLLECTION AND ANALYSIS: Data were extracted by three independent observers based on the intention to treat principle. Each study was given a quality score based on predetermined criteria. Extracted data were converted to 2X2 tables (response versus no response and antimetabolite versus placebo) and then synthesized into a summary test statistic using the pooled odds ratio and 95% confidence intervals as described by Cochran and Mantel and Haenszel ('Odds Ratio' in MetaView). MAIN RESULTS: The odds ratio of a response to azathioprine or 6-mercaptopurine therapy compared with placebo in active Crohn's disease was 2.36 (95% CI 1.57-3.53). This corresponded to a number needed to treat of about 5 to observe an effect of therapy in one patient. When the two trials using 6-mercaptopurine in active disease were excluded from the analysis, the odds ratio of response was 2.04 (CI 1.24 - 3.35). Treatment >/= 17 weeks increased the odds ratio of a response to 2.51 (CI 1.63-3. 88). A steroid sparing effect was seen with an odds ratio of 3.86 (CI 2.14 - 6.96), corresponding to a number needed to treat of about 3 to observe steroid sparing in one patient. Adverse events requiring withdrawal from a trial, principally allergy, leukopenia, pancreatitis, and nausea were increased on therapy with an odds ratio of 3.01 (CI 1.30 - 6.96). The number needed to treat to observe one adverse event in one patient treated with azathioprine or 6-mercaptopurine was 14. REVIEWER'S CONCLUSIONS: Azathioprine and 6-mercaptopurine are effective therapy for inducing remission in active Crohn's disease. The odds ratio of response increases after >/= 17 weeks of therapy, suggesting that there is a minimum length of time for a trial of azathioprine or 6-mercaptopurine therapy. Adverse events were more common among patients on therapy.

Corticosteroids for maintenance of remission in Crohn's disease.

BACKGROUND: The efficacy of corticosteroids in the setting of maintenance therapy for Crohn's disease has never been clearly demonstrated. It would be important to determine, based upon the currently available data from controlled trials, if the use of chronic corticosteroid therapy is of benefit in patients with quiescent Crohn's disease or if there is an identifiable subgroup of Crohn's disease patients, such as those in whom therapy cannot be successfully tapered, who might benefit from such treatment. OBJECTIVES: To evaluate the effectiveness and safety of conventional systemic corticosteroid therapy in maintaining clinical remission in Crohn's disease. SEARCH STRATEGY: A computer-assisted search of the on-line bibliographic database MEDLINE of studies published in English, French, Spanish, Italian and German between 1966 and July, 2003. Manual searches of the reference lists from the potentially relevant studies were performed in order to identify additional studies that may have been missed using the computer-assisted search strategy. Proceedings from major gastrointestinal meetings were also manually searched from 1985 to 2003 in order to identify unpublished studies. The Cochrane Central Register of Controlled Trials and the Inflammatory Bowel Disease Review Group Specialized Trials Register were also searched. SELECTION CRITERIA: Randomized double-blind placebo-controlled trials involving patients of any age with Crohn's disease in clinical remission as defined by a CDAI < 150 or by the presence of no symptoms or only mild symptoms at the time of entry into the trial. The experimental treatment consisted of oral conventional corticosteroid therapy (excluding budesonide, fluticasone, etc). Clinical disease relapse was used as the outcome measure of interest. DATA COLLECTION AND ANALYSIS: Eligible studies were selected by 4 reviewers and data were extracted onto standardized data extraction forms. Disagreements in eligibility or data extraction were resolved by consensus. Data were converted into individual 2x2 tables for each study. The presence of significant heterogeneity among studies was tested using the chi-square test. The 2x2 tables were synthesized into a summary test statistic using the pooled odds ratio and 95% confidence intervals as described by Cochran and Mantel and Haenszel (the 'odds ratio' in MetaView). A fixed effects model was used for the pooling of data. MAIN RESULTS: Four studies were initially judged as being eligible for inclusion. After obtaining additional information on one of the studies it was excluded because it was not double-blind. The total number of subjects included in the analysis at the time points of 6, 12 and 24 months were 142, 131 and 95 for the corticosteroid group and 161, 138 and 87 for the control group. The odds ratios for relapse on active treatment and the corresponding 95% confidence intervals were 0.71 (0.39, 1.31), 0.82 (0.47, 1.43) and 0.72 (0.38, 1.35) at 6, 12 and 24 months. REVIEWER'S CONCLUSIONS: The use of conventional systemic corticosteroids in patients with clinically quiescent Crohn's disease does not appear to reduce the risk of relapse over a 24 month period of follow-up. This review updates the existing review of corticosteroids for maintaining remission of Crohn's disease which was published in the Cochrane Library (Issue 2, 2003).

[Treatment of Crohn's disease with azathioprine or 6-mercaptopurine. Retrospective study of 126 cases]. / Traitement de la maladie de Crohn par l'azathioprine ou la 6-mercaptopurine. Etude rétrospective chez 126 malades.

Over the past 15 years (1974-1989), 126 patients with Crohn's disease received azathioprine (n = 123) or 6-mercaptopurine (n = 3). Seven patients were lost of follow-up during the first month and were not analyzed. Among the 119 patients analyzed (52 men, 67 women, mean age 31.6 years), the median duration of treatment was 9.1 months (range: 8 days to 15 years). Most of the 109 patients with active disease at the beginning of the immunosuppressive therapy were either steroid-dependent (n = 63) or steroid-resistant (n = 23); 19 had frequent relapses and/or extensive involvement of the gastrointestinal tract; 4 had severe perianal disease. Among these 109 patients, 25.4, 51, 60.4 and 64.4 percent were in clinical remission at 3, 6, 9 and 12 months (life-table analysis) respectively. There was no difference in outcome of patients with colonic, ileocolonic or small intestinal involvement. Steroid-resistant patients fared better than steroid-dependent patients (81 percent vs 59 percent of remission within the first year; p less than 0.001). In the 62 patients with quiescent disease treated with azathioprine or 6-mercaptopurine, previous remission had been achieved with immunosuppressive therapy in 52, 8 were treated after a bowel resection which was assumed to be curative; 2 had achieved remission after total parenteral nutrition. In these patients, the percentages of relapse were 15.3 at the end of the first year and 20.3 at the end of the second year. Among the 8 patients treated with azathioprine after bowel resection, only one relapse occurred 1.5 months after surgery. Nineteen percent of the patients had adverse reactions that required discontinuation of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

[Measurement of ileal absorption of bile salts with the selenium 75 labelled homotaurocholic acid test. Validation and clinical significance]. / Mesure de l'absorption iléale des sels biliaires par le test à l'homotaurocholate marqué au sélénium 75. Validation et signification clinique.

OBJECTIVES AND METHODS: The performances and the clinical significance of a simplified version of the 75SeHCAT test which measures ileal absorption of bile salts were assessed in 23 healthy subjects and 106 patients. Corporeal retention of the marker was measured using an uncollimated gamma-camera. RESULTS: In healthy subjects, the 75SeHCAT retention was lower in the group of 9 with an osmotic diarrhoea induced by a PEG solution than in the group of 14 tested in normal conditions (22 +/- 4% vs 44 +/- 4%; P < 0.01). The reproducibility of the measure was good (r = 0.93; P < 0.001). The sensibility and specificity of the test for the diagnosis of ileal involvement were 79% and 90% respectively. Bile acid malabsorption was evidenced in 38% of patients with functional diarrhoea (59% and 28% in patients with and without previous cholecystectomy respectively; P < 0.02). In patients with fonctional diarrhoea, a correlation was evidenced between the orofaecal transit time and the 75SeHCAT retention (r = 0.66; P < 0.001) and cholestyramine improved diarrhoea in 8 out of 11 patients with 75SeHCAT malabsorption and in 2 out of 5 patients with normal test. These results show that the 75SeHCAT test is accurate and that bile acid malabsorption, frequently evidenced in functional diarrhoea, is correlated with an acceleration of intestinal transit.

[Ileal duplication in adults. Value of 99m pertechnetate scintigraphy]. / Duplication iléale de l'adulte. Intérêt de la scintigraphie au 99m pertechnétate.

Duplications of the small bowel are an uncommon group of congenital malformations whose symptoms rarely occur in adults. We report the case of a 21 year-old man who suffered during four years from symptoms related to the ulceration of ectopic gastric mucosa in an ileal duplication (spontaneously resolving peritonitis, pelvic abscess, recurrent gastrointestinal bleeding and chronic abdominal pain). Radiological and endoscopic explorations and a first laparotomy failed to provide the diagnosis. 99m pertechnetate (99mTcO4) scintigraphy demonstrated ectopic gastric mucosa and guided the radiological detection of an ileal ulceration. Injection of 99mTcO4 during a second laparotomy located the ectopic gastric mucosa at the level of a tumefaction found on the mesenteric side of the terminal ileum. Duplication was only recognized at pathological examination of the ileal resection. This case emphasizes the need to evoke a duplication in clinical circumstances like those described in this patient as well as the usefulness of 99mTcO4 in the diagnosis of such a malformation.