Signe Wildt

Objectives To evaluate the adequacy of reporting of protocols for randomised trials on diseases of the digestive system registered in http://ClinicalTrials.gov and the consistency between primary outcomes, secondary outcomes and sample size specified in http://ClinicalTrials.gov and published trials. Methods Randomised phase III trials on adult patients with gastrointestinal diseases registered before January 2009 in http://ClinicalTrials.gov were eligible for inclusion. From http://ClinicalTrials.gov all data elements in the database required by the International Committee of Medical Journal Editors (ICMJE) member journals were extracted. The subsequent publications for registered trials were identified. For published trials, data concerning publication date, primary and secondary endpoint, sample size, and whether the journal adhered to ICMJE principles were extracted. Differences between primary and secondary outcomes, sample size and sample size calculations data in http://ClinicalTrials.gov and in the published paper were registered. Results 105 trials were evaluated. 66 trials (63%) were published. 30% of trials were registered incorrectly after their completion date. Several data elements of the required ICMJE data list were not filled in, with missing data in 22% and 11%, respectively, of cases concerning the primary outcome measure and sample size. In 26% of the published papers, data on sample size calculations were missing and discrepancies between sample size reporting in http://ClinicalTrials.gov and published trials existed. Conclusion The quality of registration of randomised controlled trials still needs improvement.

Background and aims: To investigate the clinical effect of treatment with Lactobacillus acidophilus La-5 and Bifidobacterium animalis subsp. lactis BB-12 (Probio-Tec AB-25) to maintain remission in patients with ulcerative colitis. Methods: Patients with left-sided ulcerative colitis in remission — including proctitis and at least one relapse within the last year were randomised (2:1) in a double-blind placebo-controlled study to Probio-Tec AB-25 or placebo for 52 weeks. The patients were evaluated clinically, endoscopically and histologically at entry and if relapsing. No other medication for ulcerative colitis than the study drug was allowed during the study. Primary endpoint was maintenance of clinical remission, secondary endpoints comparisons of days to relapse, and safety and tolerability of the study drug. The concentrations of the probiotic bacterial strains in stool were analysed in a subset of patients. Results: Thirty-two patients were randomised. Twenty patients received Probio-Tec AB-25 and twelve patients received placebo. Five patients (25%) in the Probio-Tec AB-25 group and one patient (8%) in the placebo group maintained remission after 1 year of treatment (p = 0.37). The median time to relapse was 125.5 days (range 11–391 days) in the probiotic group and 104 days (range 28–369 days) in the placebo group respectively, (p = 0.683). Probio-Tec AB-25 was overall well tolerated. Conclusions: In this small randomised placebo-controlled trial no significant clinical benefit of Probio-Tec AB-25 could be demonstrated in comparison with placebo for maintaining remission in patients with left-sided ulcerative colitis. A difference may be achieved in larger studies, but the clinical significance of this would be questionable. This study was registered in ClinicalTrial.gov (NCT00268164).

Collagenous colitis (CC) is an inflammatory bowel disease of unknown aetiology and pathogenesis. In ulcerative colitis and Crohn's disease, prostaglandins may be involved in the pathogenesis of inflammation, and increased expression of cyclo-oxygenase-2 (COX-2) has been detected. The purpose of this study was to examine the presence and cellular localization of COX-2 in colonic mucosa of patients with CC. Using immunohistochemistry, immunoflouresence and Western blot analysis, COX-2 expression was evaluated in colonic mucosal biopsies from 10 patients with active untreated CC, and compared with samples from eight normal controls, and samples from eight patients with ulcerative colitis or Crohn's disease. Specimens from patients with CC expressed COX-2 protein in increased amounts compared with controls, but similar to patients with ulcerative colitis and Crohn's disease. COX-2 expression was localized to the mononuclear cells of the lamina propria. COX-2 expression was most evident in macrophages. Co-localization of COX-2 and macrophages was increased in number in comparison with controls. In conclusion COX-2 is expressed in increased amounts primarily in the macrophage subpopulation of the inflammatory infiltrate of lamina propria in CC. Increased recruitment of macrophages, increased expression of COX-2 and increased prostaglandin synthesis may be involved in the pathogenesis of CC.

Objectives To evaluate the excretion of the inflammatory and metabolic faecal markers calprotectin, lactoferrin, and short-chain fatty acids in symptomatic and quiescent collagenous colitis. Methods Faecal samples from 21 patients with active collagenous colitis, 12 patients retested in remission, and 13 controls were analysed. Calprotectin was determined using an enzyme-linked immunosorbent assay. Lactoferrin was estimated by a latex agglutination test. Short-chain fatty acids were determined by steam distillation followed by gas–liquid chromatography. Results Calprotectin was increased in patients with active collagenous colitis [80 μg/g (6.25–1899)] (median and range) compared with patients with quiescent collagenous colitis [26 μg/g (6.25–340)], P=0.025 and controls [6.25 μg/g (6.25–99)], P=0.002. Eight patients (38%) with active collagenous colitis had normal levels of calprotectin. Lactoferrin was detected in one patient only. Concentrations of total short-chain fatty acids did not differ in patients with active collagenous colitis compared with quiescent collagenous colitis or controls (P=0.75), whereas concentrations of the branched-chain fatty acids were decreased in patients with active collagenous colitis versus controls (PPP<0.05). Conclusion Faecal calprotectin was increased in collagenous colitis; however, increased excretion was not a universal finding limiting the use of calprotectin as an inflammatory marker in collagenous colitis. Faecal lactoferrin was almost undetectable. Luminal fermentative conditions are altered in collagenous colitis. Fermentative alterations could be secondary to changes in substrate availability and intestinal transit time.

Background. Probiotic treatment may be effective in diseases involving gut microflora and intestinal inflammation. In collagenous colitis (CC), a poten

Objective. Collagenous colitis (CC) is a chronic inflammatory bowel disease that affects the colon. However, some patients with CC present with accompanying pathologic small-bowel manifestations such as coeliac disease, defects in bile acid absorption and histopathologic changes in small-intestinal biopsies, indicating that CC is a pan-intestinal disease. In small-intestinal disease, the intestinal barrier function may be impaired, and the permeability of the small intestine altered. The purpose of this research was to study small-bowel function in patients with CC as expressed by intestinal permeability. Material andmethods. Ten patients with CC and chronic diarrhoea participated in the study. Coeliac disease was excluded by small-bowel biopsy and/or serology. Intestinal permeability was assessed as urinary excretion (ratios) 2, 4 and 6 h after ingestion of ¹⁴C-labelled mannitol (¹⁴C-mannitol) and ^99mTc-labelled diethylenetriamine-pentaacetic acid (^99mTc-DTPA). Data were compared with the results from healthy controls. Results. No difference was found between groups in urinary excretion of ¹⁴C-mannitol and ^99mTc-DTPA after 2, 4 or 6 h, respectively. Likewise, no significant differences in the ^99mTc-DTPA/¹⁴C-mannitol ratios between patients and controls were detected after 2 h: 0.030 (0.008–0.130) versus 0.020 (0.007–0.030), p=0.19, after 4 h: 0.040 (0.009–0.180) versus 0.020 (0.008–0.040), p=0.14 or after 6 h: 0.040 (0.012–0.180) versus 0.020 (0.010–0.040), p=0.17. Conclusions. No alterations in intestinal permeability in patients with CC could be demonstrated. Impairment of the integrity of the mucosa of the small bowel and the presence of a general dysfunction of the small intestine in patients with CC seem unlikely.

Bile acid malabsorption (BAM), a cause of chronic diarrhoea, can be diagnosed by the SeHCAT test. The purpose of this study was to evaluate the usefulness of SeHCAT testing by assessing the extent of BAM and describing the clinical characteristics in a group of patients with chronic diarrhoea. Clinical outcome after treatment with cholestyramine was also evaluated. During a 5-year period (1997-2001) the SeHCAT test was performed in 135 patients in whom a primary programme for diagnostic evaluation of chronic diarrhoea had not revealed a cause. File data from 133 patients could be evaluated. In 44% of patients, bile acid absorption was normal with SeHCAT retention > or = 15%. Impaired SeHCAT retention was found in 56%. All patients with ileocaecal resections had retention values < 10%. Patients with microscopic colitis presented with BAM in 39%. Only one patient with idiopathic BAM presented with steatorrhoea as opposed to 11 patients with type 1 and 3 BAM. Patients with idiopathic BAM and/or SeHCAT retention values < 5% had the best response to treatment with cholestyramine. The SeHCAT test is of value in evaluation of patients with chronic diarrhoea as a second-line investigation with a high diagnostic yield. The only a priori parameter to predict BAM was the existence of ileocaecal resections. The result of the SeHCAT test seems to predict the benefit of treatment with cholestyramine.

A case of Kingella kingae osteomyelitis in a 1-year-old child is described. Kingella kingae osteoarticular infections in children and the difficulties of isolating this slow growing, fastidious bacterium are discussed.