Faecal stasis and diverticular disease in ulcerative colitis

The incidence of faecal stasis and of diverticular disease has been studied in a group of 399 patients with ulcerative colitis. Sixty-one patients had faecal stasis and 23 patients had diverticular disease. Pathological studies demonstrated an increase in the thickness of the inner spiral muscle in colitis patients with faecal stasis. The thickening was not as great as that seen in diverticular disease. Preliminary studies on the motility patterns in patients with faecal stasis show a higher mean activity in the pelvic colon than in normals but not as great as that seen in diverticular disease. Pressure studies in patients with faecal stasis have shown hypotonia in the proximal colon associated with dilatation.The possible significance of these results is discussed. It is suggested that ulcerative colitis may initiate a motility disturbance which leads to muscle thickening similar to that in diverticular disease. Diverticula associated with ulcerative colitis are usually not involved in the mucosal inflammatory process.     

Faecal mucus degrading glycosidases in ulcerative colitis and Crohn's disease.

Because the normal faecal flora includes bacteria which can produce mucus-digesting glycosidases, it follows that increased digestion of colonic mucus by these bacterial enzymes could be important in the pathogenesis of ulcerative colitis. Faecal activities of potential mucus-degrading glycosidases have therefore been assayed in samples from patients with inflammatory bowel disease and normal controls. The enzymes alpha-D-galactosidase, beta-D-galactosidase, beta-NAc-D-glucosaminidase alpha-L-fucosidase and neuraminidase were assayed. Considerable glycosidase activity was present in most faecal samples. Similar activities of all the enzymes assayed were found in faeces from patients with ulcerative colitis, Crohn's disease and normal controls and there was no significant correlation with disease activity. These results imply that relapse of ulcerative colitis is not initiated by increased degradation of colonic mucus by faecal glycosidases but do not exclude a role for bacterial mucus degradation in the pathogenesis of ulcerative colitis.     

Faecal excretion of bicarbonate in ulcerative colitis

The normal colon absorbs water, sodium and chloride and secretes potassium and bicarbonate. In ulcerative colitis (UC), modifications occur in the absorption of water, sodium and chloride, whereas the secretion of potassium remains unchanged. There appear to be no data in the literature on bicarbonate secretion. Since some 25% of chloride absorption is coupled with bicarbonate secretion by an anion exchange mechanism, the impairment in chloride absorption should be accompanied by modifications in bicarbonate secretion. Faecal bicarbonate was therefore measured in 20 patients with active UC and 15 normal control subjects. Faecal pH, pCO2 and electrolytes (Na+, K+, Cl-, HCO3-), blood acid-base balance, urinary pH and bicarbonate were determined on the same day in all patients. Faecal pH and bicarbonate were significantly reduced in UC versus controls: pH 6.06 +/- 0.39 versus 6.52 +/- 0.43; HCO3- 8.4 +/- 5.2 versus 34.6 +/- 12.3 mEq/l (mean +/- SD), whereas sodium and chloride were increased. Faecal potassium concentration was normal, but potassium output was increased. Metabolic alkalosis was observed in 8 patients and a normal acid-base balance in the remaining 12. Urinary pH was acid and urinary bicarbonate negligible in all patients. No correlation was observed between plasma, faecal and urinary bicarbonate. Data emerging from this study show that the faecal excretion of bicarbonate is reduced in patients with active UC. A possible explanation for this finding may be impairment of the colonic anion exchange mechanism induced by inflammation of the mucosa. The role of organic anions is also hypothesized. The acid-base balance does not seem to be directly affected by the decrease in faecal bicarbonate loss.     

Individual fecal alpha 1-antitrypsin excretion reflects clinical activity in Crohn's disease but not in ulcerative colitis.

BACKGROUND/AIMS: The natural course of fecal alpha 1-antitrypsin (AAT) excretion was assessed in patients with inflammatory bowel disease (IBD) to evaluate its role in monitoring their clinical disease activity. METHODOLOGY: A prospective cohort pilot study was performed in 9 patients with Crohn's disease (CD) and 3 individuals with ulcerative colitis (UC). Subjects were investigated at regular monthly intervals for about one year for (a) parallel AAT stool and serum concentrations by standard immunonephelometry, and (b) for clinical disease activity by Crohn's Disease Activity Index (CDAI) in CD patients, and by Clinical Activity Index (CAI) in UC subjects. Absolute results during follow-up were each referred to individual findings at study entry as relative results. RESULTS: While absolute fecal AAT concentration did not correlate with disease activity indices (p > 0.26), relative fecal AAT concentration significantly correlated to concurrent relative CDAI score in CD patients (p < 0.001, r = 0.67), but not to relative CAI score in UC subjects (p = 0.92). Monthly intraindividual variation of fecal AAT excretion did not predict development of either disease activity index (p > 0.14). CONCLUSIONS: Individual fecal AAT excretion closely reflects clinical course in CD subjects, but not in UC patients. It does not predict symptomatic deterioration in these individuals, at least on a short-term basis.     

Interleukin-6 is associated with steroid resistance and reflects disease activity in severe pediatric ulcerative colitis

Background and aimApproximately one third of patients with acute severe ulcerative colitis (ASC) will fail intravenous corticosteroids (IVCS). Predicting response to IVCS to initiate early salvage therapy remains challenging. The aim of this study was to evaluate the role of serum inflammatory cytokines in ASC and determine their predictive utility with IVCS treatment failure.MethodsThis preplanned ancillary study, part of the prospective multicenter OSCI study, evaluated pediatric ASC in North America. Serum samples were obtained from 79 children admitted for ASC on the third day of IVCS treatment. Twenty-three (29%) patients required second-line therapy. ELISA-based cytokine arrays were used [TNF-α, IFN-γ, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, and IL-17], selected based on a systematic literature search.ResultsIn univariate analysis, only IL-6 was significantly different between responders and non-responders (P = 0.003). The risk for IVCS failure increased by 40% per each pg/mL increase in IL-6 level. Factor analysis found IL-6 to be associated with IL-17, suggesting involvement of the T-helper (T_H)17 pathway. In a multivariate analysis, disease activity [judged by the Pediatric UC Activity Index (PUCAI)] assumed all the association with the treatment outcome while IL-6 was no longer significant (P = 0.32; PUCAI score P < 0.001).ConclusionsWhile IL-6 strongly predicted IVCS failure, it likely reflects disease activity and not direct interference with corticosteroid pathway. Nonetheless, IL-6 levels may have a role in predicting IVCS response in severe pediatric UC for treatment decision-making or potentially in medical intervention by virtue of anti-IL-6 antibodies in severe UC.     

Comparing disease activity indices in ulcerative colitis

BackgroundComparisons between disease activity indices for ulcerative colitis (UC) are few. This study evaluates three indices, to determine the potential impact of inter-observer variation on clinical trial recruitment or outcome as well as their clinical relevance.MethodsOne hundred patients with UC were prospectively evaluated, each by four specialists, followed by videosigmoidoscopy, which was later scored by each specialist. The Simple Clinical Colitis Activity (SCCAI), Mayo Clinic and Seo indices were compared by assigning a disease activity category from published thresholds for remission, mild, moderate and severe activity. Inter-observer variation was evaluated using Kappa statistics and its effect for each patient on recruitment and outcome measures for representative clinical trials calculated. Clinical relevance was assessed by comparing an independently assigned clinical category, taking all information into account as if in clinic, with the disease activity assigned by the indices.ResultsInter-observer agreement for SCCAI (κ = 0.75, 95% CI 0.70–0.81), Mayo Clinic (κ = 0.72, 95% CI 0.67–0.78) and Seo (κ = 0.89, 95% CI 0.83–0.95) indices was good or very good as was the agreement for rectal bleeding (κ = 0.77) and stool frequency (κ = 0.90). Endoscopy in the Mayo Clinic index had the greatest variation (κ = 0.38). Inter-observer variation alone would have excluded up to 1 in 5 patients from recruitment or remission criteria in representative trials. Categorisation by the SCCAI, Mayo Clinic and Seo indices agreed with the independently assigned clinical category in 61%, 67% and 47% of cases respectively.ConclusionsTrial recruitment and outcome measures are affected by inter-observer variation in UC activity indices, and endoscopic scoring was the component most susceptible to variation.     

Assessment of disease activity in pediatric ulcerative colitis

To date, we encounter more and more pediatric patients with ulcerative colitis (UC). For yet unclear reasons, UC in pediatric patients seems to be a more aggressive and extensive disease than in their adult counterparts. In the majority of pediatric patients, the disease presents as pancolitis. The severity of the disease is reflected in the high use of corticosteroids and immunosuppressants and a high rate of surgery for medically refractory patients. The means by which to assess disease activity or to accurately predict its course are far from optimal. This review summarizes the current knowledge on the means for assessing UC activity in children. Research for developing new tools by which to monitor and forecast disease activity, are needed in all areas including invasive endoscopy, clinical evaluation, and treatment follow-up.     

Bronchopulmonary disease in ulcerative colitis.

Two cases of ulcerative colitis are described: a 33-year-old woman who developed widespread bronchiectasis 7 months after undergoing colectomy, and a 72-year-old man whose colonic disease began coincidentally with the appearance of diffuse interstitial pulmonary infiltrates. In both cases, clinical correlation and common patterns of response of lung and bowel diseases suggested that the co-existence of these two pathologies might not be merely a casual relation.     

HLA-DR expression and disease activity in ulcerative colitis

In 12 patients with active ulcerative colitis (UC) the rectal epithelial cells were analyzed for HLA-DR antigens by an immunohistochemical technique. The clinical, rectoscopic, and histologic stages were also determined. The investigations were carried out at the beginning of the study and 2 weeks and 3 months later. The rectal epithelial cells were HLA-DR-positive in all patients at the first two examinations. After 3 months five patients had changed to an HLA-DR-negative stage, whereas the other seven patients remained HLA-DR-positive. Closer analyses showed that expression/nonexpression of HLA-DR antigens on rectal epithelial cells of patients with UC could not be predicted from the clinical, rectoscopic, or histologic findings. HLA-DR expression is normally restricted to immunocompetent cells. The presence of HLA-DR antigens on epithelial cells may be a consequence of immunological reactions. Whether HLA-DR-positive cells have a specific function is unknown.     

Plasma interleukin-18 reflects severity of ulcerative colitis

AIM: The aim of this study was to evaluate the association between ulcerative colitis activity and plasma or mucosal concentrations of interleukin (IL)-18. METHODS: 11-18 concentrations were measured in plasma and mucosal samples from 15 patients with active ulcerative colitis (UC). RESULTS: The mean plasma concentration of IL-18 measured in all patients (422±88 pg/mL) doubled the mean value in healthy controls (206±32 pg/mL); however, the difference was not statistically significant. Plasma IL-18 levels revealed a significant positive correlation with scored endoscopic degree of mucosal injury, disease activity index, clinical activity index and C-reactive protein concentration. The mean concentration of plasma IL-18 was significantly higher in patients with severe ulcerative colitis (535±115 pg/mL) than in patients with mild ulcerative colitis (195±41 pg/mL), and in healthy controls. Although the mucosal mean IL-18 concentration in severe ulcerative colitis (2 523±618 pg/mg protein) doubled values observed in mild one (1347±308 pg/mg protein), there was no statistically significant difference. CONCLUSION: Plasma IL-18 can be considered as a surrogate marker helpful in evaluation of ulcerative colitis activity.     

Oral fluticasone propionate in active distal ulcerative colitis.

Fluticasone propionate is a new corticosteroid with low systemic bioavailability. This study reports the outcome of a double blind clinical trial comparing oral fluticasone propionate (5 mg four times daily) with placebo for the treatment of active distal ulcerative colitis. Sixty patients were treated for four weeks, with assessments at two and four weeks. One patient was withdrawn when she was found to have amoebiasis. Thus, results are presented for 29 patients who received placebo and 30 who received fluticasone propionate. The two groups were well matched for age, sex, length of history, and extent of disease. After four weeks of therapy the clinical, sigmoidoscopic, and histological responses were similar in the two groups. It is concluded that fluticasone propionate (5 mg four times daily) is not effective treatment for active distal ulcerative colitis.