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Background and aims: Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are complex genetic disorders. CARD15/NOD2, a member of the Ced4 super-family which includes Apaf-1 and [...]

OBJECTIVE: It has been suggested that, in inflammatory bowel disease, cytomegalovirus behaves in the intestine as a nonpathogenic bystander, and even its finding in intestinal mucosa has unclear clinical relevance. We report our experience with a small series of patients with refractory inflammatory bowel disease and cytomegalovirus infection and their clinical outcome. METHODS AND RESULTS: Nine patients with moderate-severe attacks of inflammatory bowel disease did not respond to i.v. prednisone (I mg/kg/day) for a mean of 24 days. Four of these patients were further treated with i.v. cyclosporine A (4 mg/kg/day). Cytomegalovirus infection was diagnosed in two patients after resection for treatment failure. In the remaining patients, cytomegalovirus infection was diagnosed in endoscopic mucosal biopsies and i.v. ganciclovir was then administered at a dose of 10 mg/kg/day for 2-3 wk. Five of these patients went into clinical remission, allowing corticosteroid and cyclosporine A discontinuation. Follow-up biopsies were performed and in all cases cytomegalovirus could not be detected in the colonic tissue. Two patients needed to be treated with intravenous cyclosporine A after antiviral therapy because of persistence of clinical symptoms despite the elimination of cytomegalovirus infection. CONCLUSIONS: Cytomegalovirus infection may play a role in the natural history of refractory inflammatory bowel disease and in some of its complications. The clearance of cytomegalovirus in colonic mucosa may lead some of these patients to remission. [ABSTRACT FROM AUTHOR]

Serologic markers, HLA-DQ2 haplotype, and clinical features suggestive of celiac disease were studied to assess their diagnostic value in a multicentric study to detect celiac disease in 675 first-degree relatives of 227 celiac probands. Serum IgA-class anti-endomysium and IgA-class anti-gliadin antibodies were positive in 5.8% and 1.9% of relatives, respectively. HLA-DQ2 haplotype was present in 64% of relatives, and the overall rate of celiac disease diagnosed by intestinal biopsy was 5.5%. The frequency of HLA-DQ2 in the celiac patients and controls was 93% and 18%, respectively. The most frequent clinical features--diarrhea, anemia, food intolerance, and growth retardation--were not present in one third of the celiac disease relatives. We conclude that the assessment of IgA-class anti-endomysium antibodies alone seems a reasonable approach for screening celiac disease in relatives and cannot be replaced by an accurate clinical anamnesis. HLA-DQ2 haplotype may identify the population with a high genetic susceptibility to celiac disease. [ABSTRACT FROM AUTHOR]

The usefulness of scintigraphy with In-oxinelabelled autologous leucocytes was investigated in 27 patients with inflamatory bowel disease (IBD): 16 with ulcerative colitis and 11 with Crohn's disease. Scans were performed 2-4 h (early scan) and at 24 h (late scan) after leucocyte reinjection. No false-negative results occurred in the early scan; however, in the late scan, 2 patients with Crohn's disease had a normal scintigram. A new index of activity ( I) based on the number and relative activity of abnormal In-leucocyte zones was used for scan quantitation. All patients with clinically active IBD had I≧2. The scintigraphic index showed a significant correlation with the Harvey clinical index, especially in patients with ulcerative colitis. Our results suggest that an early scan (2-4 h) provides useful information in cases of IBD, and that I≧2 is indicative of the degree of disease activity in such patients. [ABSTRACT FROM AUTHOR]

Objective: Butyrate enemas may be effective in the treatment of active distal ulcerative colitis. Because colonic fermentation of Plantago ovata seeds (dietary fiber) yields butyrate. the aim of this study was to assess the efficacy and safety of Plantago ovata seeds as compared with mesalamine in maintaining remission in ulcerative colitis. Methods: An open label, parallel-group, multi-center, randomized clinical trial was conducted. A total of 105 patients with ulcerative colitis who were in remission were randomized into groups to receive oral treatment with Plantago ovata seeds (10 g b.i.d.), mesalamine (500 m t.i.d.), and Plantago ovata seeds plus mesalamine at the same doses. The primary efficacy outcome was maintenance of remission for 12 months. Results: Of the 105 patients, 102 were included in the final analysis. After 12 months, treatment failure rate was 40% (14 of 35 patients) in the Plantago ovata seed group, 35% (13 of 37) in the mesalamine group, and 30% (nine of 30) in the Plantago ovata plus mesalamine group. Probability of continued remission was similar (Mantel-Cox test, p = 0.67; intent-to-treat analysis). Therapy effects remained unchanged after adjusting for potential confounding variables with a Cox's proportional hazards survival analysis. Three patients were withdrawn because of the development of adverse events consisting of constipation and/or flatulence (Plantago ovata seed group = 1 and Plantago ovata seed plus mesalamine group = 2). A significant increase in fecal butyrate levels (p = 0.018) was observed after Plantago ovata seed administration. Conclusions: Plantago ovata seeds (dietary fiber) might be as effective as mesalamine to maintain remission in ulcerative colitis. [ABSTRACT FROM AUTHOR]

Objectives: Few studies have assessed the IgA antineutrophil cytoplasmic antibody (ANCA) positivity in ulcerative colitis patients and there is no information about factors related to its synthesis and its status after colectomy. The aims of the study were to assess the serum IgA ANCA prevalence in ulcerative colitis patients, both nonoperated and operated, and to determine the clinical factors related to this positivity. Methods: Fifty-four ulcerative colitis patients, 63 ulcerative colitis colectomized patients (32 with Brooke's ileostomy and 31 with ileal pouch anal anastomosis), and 24 controls were studied. Antineutrophil cytoplasmic antibodies were detected by specific indirect immunofluorescent assays. Results: The percentage of IgA ANCA was significantly higher in patients with ileal pouch anal anastomosis (45%) than in patients with Brooke's ileostomy (22%). There were no differences related to the presence of pouchitis in ileal pouch anal anastomosis patients. Patients with nonoperated extensive colitis (47%) had a significantly higher percentage of IgA ANCA than patients with proctitis (19%). Total percentage of ANCA (IgA and/or IgG) tended to be higher in ulcerative colitis and in patients with ileal pouch anal anastomosis than in patients with Brooke's ileostomy. However, in ileal pouch anal anastomosis patients, ANCA positivity was mainly due to exclusive IgA production. Conclusions: A substantial percentage of ulcerative colitis patients, and especially colectomized patients with ileal pouch anal anastomosis, had IgA ANCA, suggesting that ANCA production in ulcerative colitis might be stimulated by an immune reaction in the intestinal mucosa. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship of sugar malabsorption to the development of clinical symptoms in functional bowel disease. Methods: Twenty-five consecutive outpatients [five men, 20 women; mean age 38.7 ± 2.6 (SEM) yr] with functional bowel disease and symptoms suggestive of carbohydrate malabsorption were studied. Twelve healthy subjects [six men, six women; mean age 35.7 ± 3.7 (SEM) yr] acted as the control group. Sugar malabsorption was assessed by breath-hydrogen test after an oral load of various solutions containing lactose (50 g), fructose (25 g), sorbitol (5 g), fructose plus sorbitol (25+5 g), and sucrose (S0 g). The severity of symptoms developing after sugar challenge was studied. In addition, the effect on clinical symptoms of a diet free of the offending sugars, compared to a low-fat diet, was assessed. Results: Frequency of sugar malabsorption was high in both patients and controls, with malabsorption of at least one sugar in more than 90% of the subjects. Median symptom scores after both lactose [median 6; interquartile (IQ) range 3-7] and fructose plus sorbitol (median 2; IQ range 04) malabsorption were significantly higher than after sucrose load (median 1; IQ range 0-1.5) in functional bowel disease patients (p = 0.001 and p = 0.007, respectively). However, there were no differences in healthy controls. In addition, symptoms score after both lactose and fructose plus sorbitol malabsorption was significantly higher in patients than in control subjects (p = 0.02 and p = 0.008, respectively). On the other hand, H2 production capacity, as measured following lactulose load, was significantly higher in patients than in controls. The clinical symptoms improved in 40% of the evaluated patients after restriction of the offending sugars. Conclusions: These results suggest that sugar malabsorption may be implicated in the development of abdominal distress in at least a subset of patients with functional... [ABSTRACT FROM AUTHOR]

Total plasma fatty acids were measured in 101 cirrhotic inpatients (64 men, 37 women, aged 64.3 ±1 .2 (SEM) yr; range, 34-80) who were subsequently followed for survival for a mean of 14.8 ±1 .0 months. Data on plasma fatty acids have been published elsewhere. Individual values of these variables were categorized in a binary fashion using the 5th or the 95th percentiles of a group of 44 well-nourished healthy controls (24 men, 20 women, aged 51.3 ± 2.1 yr; range, 32-76) as the cutoff limit. Forty-nine patients died during follow-up (2-yr cumulative probability of survival, 52%). Deficiency of palmitate, dihomo-τ-linolenate, and arachidonate (values below the 5th percentile) were univariately associated with death (long-rank test). However, after a multivariate analysis (Cox's proportional hazards regression), only the existence of plasma arachidonate deficiency was included in the final model (β, 0.62; relative risk, 1.86; 95% CI, 1.06-3.25; p < 0.05). We conclude that arachidonic acid deficiency significantly increases the mortality risk in patients with advanced liver cirrhosis. [ABSTRACT FROM AUTHOR]

In order to identify the predictive factors of hospital mortality in cirrhotics with spontaneous bacterial peritonitis (SBP), we studied 64 patients who fulfilled the accepted diagnostic criteria. All cases were treated with cefotaxime up to 2 days after the infection was considered cured (7.7 ± 2.9 days). Eleven patients (17%) died while in hospital, six of them before SBP was cured. After uni- and multivariate analyses, only seven routine clinical, biological, and bacteriological variables studied were independently associated with hospital mortality. These were: the presence of upper gastrointestinal bleeding at admission (13 = 2.01), the absence of abdominal pain as presenting symptom (P = --1.29), the polymorphonuclear count (%) in the ascites (β = 0.48), prothrombin rate (β = --0.22), and serum Na (β = -0.64), creatinine (β = 0.50), and cholesterol (β = -0.68). When the equation obtained was computed in a randomly selected sample of the patients studied, it correctly predicted the outcome in 92.3% of the cases. We conclude that short-term outcome of SBP patients depends on the existence of recent gastrointestinal bleeding, the severity of SBP, and the degree of liver and renal failure. The prognostic value of this model needs prospective validation in a new series of patients. [ABSTRACT FROM AUTHOR]

To ascertain the role of total enteral nutrition, compared with total parenteral nutrition, as adjunct therapy to steroids in patients with severe acute ulcerative colitis, a prospective randomized trial was conducted in 42 of such patients. Inclusion criteria were the persistence of a moderate or severe attack of the disease (Truelove's index) after 48 h on full steroid treatment (prednisone 1 mg/kg/day). Patients were randomized to receive polymeric total enteral nutrition or isocaloric, isonitrogenous total parenteral nutrition as the sole nutritional support. Remission rate and need for colectomy were similar in both groups. No significant changes in anthropometric parameters were observed in either nutritional group at the end of the study. Median increase in serum albumin was 16.7% (-0.5% to +30.4%) in the enteral feeding group, and only 4.6% (-12.0% to +13.7%) in the parenteral nutrition patients (p = 0.019). Adverse effects related to artificial nutritional support were less frequent (9% vs. 35%, p = 0.046) and milder in enterally fed patients. Postoperative infections occurred more often with parenteral nutrition (p = 0.028). These results suggest that total enteral nutrition is safe and nutritionally effective in severe attacks of ulcerative colitis. It is also cheaper and associated with fewer complications than parenteral nutrition. Total enteral nutrition should be regarded as the most suitable type of nutritional support in these patients. [ABSTRACT FROM AUTHOR]