The frame-shift mutation of the NOD2/CARD15 gene is significantly increased in ulcerative colitis: an *IG-IBD study.
Explore the source record for details and available documents.
Carrier Proteins↗
Biomedical subjects
V Annese
Publications and source records attributed to V Annese.
Two mesalazine regimens in the prevention of the post-operative recurrence of Crohn's disease: a pragmatic, double-blind, randomized controlled trial.
BACKGROUND: The role of mesalazine in preventing the clinical recurrence of Crohn's disease after surgery has been shown in a meta-analysis of all published studies. No clear relationship, however, has been shown between dosage and response. AIM: To evaluate whether 4.0 g/day of mesalazine may offer therapeutic advantages over 2.4 g/day in the prevention of both endoscopic and clinical post-operative recurrence of Crohn's disease. METHODS: The study was a double-blind, randomized, multi-centre, prospective, controlled clinical trial. Two hundred and six patients, submitted to first or second intestinal resection for Crohn's disease limited to the terminal ileum, with or without involvement of the caecum/ascending colon, were enrolled. Of these, 101 were randomly allocated to receive 4.0 g/day of mesalazine (Asacol, Giuliani SpA, Milan, Italy) and 105 to receive 2.4 g/day, starting 2 weeks after surgery. The primary outcome was endoscopic recurrence, at 12 months after surgery. Three different degrees of endoscopic recurrence were evaluated (endoscopic scores: > 0, > 1 and > 2). The secondary outcome was clinical recurrence, defined as a Crohn's disease activity index of more than 150 points or an increase in the Crohn's disease activity index of 100 points or more. For statistical analysis, chi-square, Wilcoxon and Cox regression model tests were used, when appropriate. RESULTS: Eighty-four patients in the 4.0 g/day group and 81 patients in the 2.4 g/day group were evaluable by endoscopy. Endoscopic recurrence of > 0 was significantly higher in the 2.4 g/day group than in the 4.0 g/day group (62% vs. 46%; P < 0.04). No difference was observed between the two groups with regard to the other two endoscopic outcomes (> 1 and > 2) or clinical recurrence. CONCLUSIONS: A 4.0 g/day regimen of mesalazine does not offer a clinically significant advantage over a 2.4 g/day regimen in the prevention of post-operative endoscopic and clinical recurrence of Crohn's disease at 1 year of follow-up.
Administration, Oral↗
Genetics of inflammatory bowel disease: the beginning of the end or the end of the beginning?
Recent identification of the first susceptibility gene for Crohn's disease has led to increasing enthusiasm for the investigation and dissection of inflammatory bowel disease. In the future, identification of additional genes and careful correlation of the genetic background with clinical features of the disease will help to elucidate the causes and cure of inflammatory bowel disease. However, caution is still needed in the short term since our present knowledge has limited influence on clinical management. This review focuses on the genetic background of inflammatory bowel disease, the process of discovering the mutations of the NOD2/CARD15 gene in Crohn's disease patients, and the functional clues of the genetic variants of this gene in relation to clinical features.
Carrier Proteins↗
Topical butyrate improves efficacy of 5-ASA in refractory distal ulcerative colitis: results of a multicentre trial.
BACKGROUND: The treatment of distal ulcerative colitis, refractory to conventional 5-ASA/steroid treatment, is still a matter of debate. The present study aimed at confirming, with adequate statistical power, previous data indicating the usefulness of topical butyrate and 5-ASA in the treatment of this condition. DESIGN: Double-blind, placebo-controlled, multicentre study. A total of 51 patients with distal (< 65 cm) ulcerative colitis, refractory to topical 5-ASA/cortisone, were randomly allocated to receive topical 5-ASA 2 g and 80 mM L-1 sodium-butyrate bid (Group A; 24 patients) or 5-ASA 2 g and 80 mL saline bid (Group B; 27 patients) for 6 weeks. Sigmoidoscopy with biopsies, as well as clinical and laboratory evaluations, were carried out at enrollment and at the end of the trial. Primary endpoints: remission or marked improvement in endoscopic, histologic and clinical findings. RESULTS: Most parameters showed a significant improvement vs. baseline in both groups. Remission in six patients and improvement in 12 patients in Group A vs. one remission and 13 with improvement in Group B (P < 0.05). A significant difference in favour of Group A was recorded regarding the number of bowel movements (P < 0.01), urgency (P < 0.05) and the patients' self evaluation (P < 0.01). DISCUSSION: The combined treatment with topical butyrate and 5-ASA is significantly more effective than 5-ASA alone in the management of refractory distal colitis. Further improvements in the treatment of refractory distal ulcerative colitis may be feasible based on the identification of patient subgroups and the association of two or more active drugs. Butyrate may well be one of them.
Adult↗
Linkage of ulcerative colitis to the pericentromeric region of chromosome 16 in Italian inflammatory bowel disease families is independent of the presence of common CARD15 mutations.
Explore the source record for details and available documents.
Alleles↗
[Neuropsychological tests, MRI and SPECT in the evaluation of CNS involvement in SLE].
OBJECTIVE: To assess the agreement between presence and location of central nervous system (CNS) structural damage and neuropsychological performance. METHODS: 21 unselected SLE patients underwent a 3 hours-long battery of neuropsychological tests sampling 15 cognitive functions. A neuropsychologist hypothesized for each SLE patient the most likely site of possible involvement, according to the neuropsychological performance. Patients underwent MRI scans within 6 months (3 months before or after) from neuropsychological tests and SPECT. RESULTS: 14 of the 21 SLE patients (66.6%) were impaired in at least 1 function; among these, 7 patients (33.3%) were mildly impaired and 7 (33.3%) had more than 3 functions impaired. 10 patients (48%) had abnormal MRI scan. Negative and positive agreements between neuropsychological performance and MRI scan were detected in 15 patients (71%; ?2 with Yates' correction 6.09, p 0.007, measure K for concordance 0.44, p 0.03). All the 6 negative agreements had no records of major neurologic or psychiatric events; among the 9 positive agreements, 6 presented previous major neurologic events and 2 minor neuropsychiatric symptoms. Among the subjects with disagreement, 1 was unimpaired with positive MRI and without neuropsychiatric symptoms, 5 were mildly impaired with negative MRI. CONCLUSIONS: A detailed neuropsychological evaluation along with MRI arose as a valid method to exclude or to identify, localize and clinically interpret CNS involvement in SLE. Disagreement between MRI and neuropsychological tests was detected mainly for mild cognitive impairment that might be the expression of functional (inflammatory or ischemic) processes.
Adult↗
Oral beclometasone dipropionate in the treatment of active ulcerative colitis: a double-blind placebo-controlled study.
AIM: To evaluate efficacy and safety of oral beclometasone dipropionate (BDP) when added to 5-ASA in the treatment of patients with active ulcerative colitis. METHODS: In a 4-week, placebo-controlled, double-blind study, patients with extensive or left-sided mild to moderate active ulcerative colitis were randomized to receive oral 5-ASA (3.2 g/day) plus BDP (5 mg/day) or placebo. Clinical, endoscopic and histologic features, and haematochemical parameters were recorded at baseline and at the end of the study. RESULTS: One hundred and nineteen patients were enrolled and randomly treated with BDP plus 5-ASA (n = 58) or placebo plus 5-ASA (n = 61). Both treatment groups showed a statistically significant decrease of disease activity index (DAI) and histology score at the end of treatment (P = 0.001, each). DAI score was lower in the BDP group than in the placebo group (P = 0.014), with more patients in clinical remission in the BDP group (58.6% vs. 34.4%, P = 0.008). Serum cortisol levels significantly decreased in BDP group vs. baseline (P = 0.002), but without signs of pituitary-adrenal function depletion. A low incidence of adverse events was observed in both groups. CONCLUSIONS: Oral BDP in combination with oral 5-ASA is significantly more effective than 5-ASA alone in the treatment of patients with extensive or left-sided active ulcerative colitis.
Administration, Oral↗
Association of Crohn's disease and ulcerative colitis with haplotypes of the MLH1 gene in Italian inflammatory bowel disease patients.
Explore the source record for details and available documents.
Adaptor Proteins, Signal Transducing↗
Survival and causes of death in Italian patients with ulcerative colitis. A GISC nationwide study.
BACKGROUND: Death rate for patients with ulcerative colitis has changed over last few decades. Recent studies indicate that cumulative long-term mortality is comparable to that in general population, and that deaths may depend on causes not strictly related to colonic disease. AIM: To evaluate overall and cause-specific mortality rate in a large group of Italian patients with ulcerative colitis. METHODS: A total of 2,066 ulcerative colitis patients aged >18 years consecutively diagnosed in twenty Italian Gastroenterology Units between 1964 and 1995 were followed-up from diagnosis until 1997. Standardised Mortality Ratios and Relative Survival Ratios were calculated. RESULTS: Overall mortality of patients with ulcerative colitis was comparable to that in general population with 93 deaths observed versus 92.1 expected (standardises mortality ratio, 1.0; 95% confidence interval, 0.8-1.2). Significantly higher mortality was observed in patients under 30 years of age at diagnosis (standardised mortality ratio, 2.7; 95% confidence interval, 1.3-4.9), and in those diagnosed before 1974 (standardised mortality ratio, 2.7; 95% confidence interval, 1.1-5.7). Proctocolitis and complications from surgery were mentioned in 11 and 5 certificates, respectively. A significant excess of deaths was observed for colorectal cancer (colon: standardised mortality ratio, 3.0; 95% confidence interval, 1.0-6.9; rectum: standardised mortality ratio, 4.4; 95% confidence interval, 1.2-11.3), and haemolymphopoietic neoplasms (standardised mortality ratio, 2.8; 95% confidence interval, 1.0-6.1), in particular multiple myeloma and non-Hodgkin lymphoma. A significant deficit of deaths was observed for cancer of the respiratory system (standardised mortality ratio, 0.3; 95% confidence interval, 0.1-1.0). CONCLUSIONS: This study confirms that, also in Italy, mortality of patients with ulcerative colitis is comparable to that in general population. Only 12% of deaths were due to ulcerative colitis itself, whereas 10% of deaths were attributed to colorectal cancer. Deaths from colorectal cancer occurred, on average, 9 years after diagnosis of ulcerative colitis, suggesting that the risk of cancer is not limited to patients with long-standing colitis. As to mortality for causes unrelated to colitis, there was an excess of deaths due to malignancies of the haemolymphopoietic system.
Adult↗
Ranitidine bismuth citrate-based triple therapies after failure of the standard 'Maastricht triple therapy': a promising alternative to the quadruple therapy?
BACKGROUND: Triple therapy with proton pump inhibitor, clarythromycin, and amoxicillin has been proposed in Maastricht as the first-line treatment of H. pylori infection. AIM: To determine whether ranitidine bismuth citrate (RBC) based regimens may be used as second-line treatments after 'Maastricht therapy' failure. METHODS: A total of 285 patients with H. pylori infection were given a 7-day treatment with pantoprazole 40 mg b.d., clarythromycin 500 mg b.d., and amoxicillin 1 g b.d. Patients who were still infected were randomly given one of the following 14-day treatments: RBC 400 mg b.d. plus amoxicillin 1 g b.d. and tinidazole 500 mg b.d. (RAT group), RBC 400 mg b.d. plus amoxicillin 1 g b.d. and clarythromycin 500 mg b.d. (RAC group), and RBC 400 mg b.d. plus clarythromycin 500 mg b.d. and tinidazole 500 mg b.d. (RCT group). RESULTS: The 'Maastricht therapy' achieved an eradication rate of 59% (95% CI: 54-65) on intention-to-treat analysis. The RAT, RAC, and RCT regimens achieved eradication rates of 81% (95% CI: 67-94), 43% (95% CI: 26-60), and 62% (95% CI: 44-80), respectively, on intention-to-treat analysis. Patient compliance was optimal in RAT and RAC groups. CONCLUSION: RBC plus tinidazole and either amoxicillin or clarythromycin can be used as second-line therapies after failure of the Maastricht triple therapy.
2-Pyridinylmethylsulfinylbenzimidazoles↗
Familial expression of anti-Saccharomyces cerevisiae Mannan antibodies in Crohn's disease and ulcerative colitis: a GISC study.
OBJECTIVES: Recent studies in familial Crohn's disease (CD) have suggested that anti-Saccharomyces cerevisiae mannan antibodies (ASCAs) may represent a new specific marker of genetic susceptibility. In this study we aimed to assess the importance of ASCAs by comparing their presence in a large number of patients with sporadic and familial occurrence of CD or ulcerative colitis (UC) and their unaffected relatives. METHODS: Serum samples from 96 patients with sporadic CD, 97 patients with sporadic UC, and 50 unrelated healthy controls were tested for ASCAs by a standard ELISA method. Moreover, 73 families with two or more members affected by CD and/or UC were recruited. From these families 58 CD patients, 84 UC patients, and 216 unaffected first degree relatives were investigated. RESULTS: ASCAs were detected in 34 of 96 patients with sporadic CD (35%, p < 0.01 vs controls), 11 of 97 patients with sporadic UC (12%), and two of 50 controls (4%). ASCAs were significantly (p < 0.04) more frequent in patients with familial CD (55%) and familial UC (25%) than in sporadic cases. Moreover, ASCAs were found in 25% of unaffected relatives, and this rate did not significantly differ in CD, UC, and mixed families (28%, 26%, and 22%, respectively). CONCLUSIONS: In this study we confirm that ASCAs occur particularly frequently in CD patients, especially with the presence of a positive family history. However, they are also significantly increased in UC patients with a family history and in a considerable number of unaffected relatives of inflammatory bowel disease families, irrespective of the characteristics of their families (UC, CD, mixed, ASCA positive, and ASCA negative). The presence of ASCAs in unaffected relatives might point toward a genetic predisposition to either CD or UC.
Adolescent↗
Clinical features in familial cases of Crohn's disease and ulcerative colitis in Italy: a GISC study. Italian Study Group for the Disease of Colon and Rectum.
OBJECTIVE: Previous studies have reported genetic anticipation, genomic imprinting, and phenotypic concordance of some clinical features in familial cases of Crohn's disease (CD) and ulcerative colitis (UC). The aim of our study was to investigate the phenotypic features of affected members in a large sample of CD and UC Italian families. METHODS: In a multicenter study, CD and UC families were recruited. Affected members were questioned about date of birth, gender, age at onset of symptoms and at diagnosis, location and extension of disease, occurrence of extraintestinal manifestations, use of steroids and/or of immunosuppressive drugs, need for resective surgery, and number of relapses per year (< 1 yr or > or = 1 yr). Statistical analysis was performed with chi2, Fisher's, Mann-Whitney U, and binomial probability tests, when appropriate. RESULTS: A total of 128 families with 270 affected members were studied: 35 were CD, 64 UC, and 29 mixed families (when UC and CD affected different members). In 99 of 128 families (77%), the diagnosis was concordant. In CD families, a high concordance for localization (46%), extraintestinal manifestations (67%), need for steroids (77%), need for immunosuppressive drugs (100%), need for surgery (29%), and relapse rate (36%) was found. In UC families, a high concordance for disease extension (33%), need for steroids (47%), and relapse rate (34%) was disclosed. A higher than expected concordance for ileal localization (p < 0.4) in CD families and extensive colitis (p < 0.05) in UC families was demonstrated. A generation difference of 15-20 yr in mean ages at onset of symptoms and at diagnosis was recorded. No features of more aggressive disease in subsequent generations and no differences in gender of transmitting parents and relatives were found. CONCLUSIONS: Our study shows a high rate of concordance for diagnosis and clinical features in UC and, especially, CD families. The disease occurred 15-20 yr earlier than in previous generations without features of increased severity.
Adolescent↗
Antineutrophil cytoplasmic antibodies in inflammatory bowel disease: clinical role and review of the literature.
PURPOSE: Perinuclear antineutrophil cytoplasmic antibodies have been found consistently in patients with ulcerative colitis; however, their pathogenetic and clinical role is still uncertain. In this study we tested the prevalence of perinuclear antineutrophil cytoplasmic antibodies in a large population of patients with ulcerative colitis and Crohn's disease, with particular attention to the possible correlation with clinical features. METHODS: Perinuclear antineutrophil cytoplasmic antibody reactivity was investigated with indirect immunofluorescence in 279 patients with ulcerative colitis, 110 patients with Crohn's disease, and 252 unrelated healthy subjects. RESULTS: Perinuclear antineutrophil cytoplasmic antibodies were found in 84 of 279 patients with ulcerative colitis (30 percent), 10 of 110 patients with Crohn's disease (9 percent), and 2 of 252 healthy subjects (<1 percent; P < 0.001), respectively. Perinuclear antineutrophil cytoplasmic antibodies were significantly more frequent in patients with ulcerative colitis with higher relapse rate (43 vs. 27 percent; P < 0.002), and patients with Crohn's disease with colitis (27 vs. 2.5 percent; P < 0.0003). Perinuclear antineutrophil cytoplasmic antibodies were also significantly less frequent in patients with ulcerative colitis in remission (18 vs. 34 percent; P < 0.0025). CONCLUSIONS: In this study we confirm the relative specificity of perinuclear antineutrophil cytoplasmic antibodies, either for ulcerative colitis or for Crohn's disease involving the colon. Perinuclear antineutrophil cytoplasmic antibodies were more frequently found in patients with ulcerative colitis with a more aggressive clinical behavior; however, their presence had a limited value in identifying homogeneous subgroups of patients in our population.
Adolescent↗
Ambulatory oesophageal pH-metry. Position paper of the Working Team on Oesophageal pH-metry by the GISMAD (Gruppo Italiano di Studio sulla Motilità dell'Apparato Digerente).
In the last three decades, oesophageal pH monitoring has progressed from a physiological research tool to a routine outpatient clinical investigation in patients with suspected gastro-oesophageal reflux disease, one of the most common gastrointestinal disorders. Technological progress has considerably simplified both the procedure and the interpretation of data obtained, and there is currently reasonable consensus as to the parameters that best discriminate between physiological and pathological reflux. There remains a need for internationally agreed definitions and standards with regard to indexes to quantitate the extent and the significance of the relationship between occurrence of symptoms and reflux episodes during the examination. It is felt that national or local normal values are to be used to circumvent different eating habits and other socio-cultural differences which may influence gastro-oesophageal reflux. The reproducibility of the test appears, at present, to be at least good enough to allow classification of the patient as a pathological or physiological refluxer, albeit wide day-to-day variations seem to exist as far as concerns the extent of gastro-oesophageal reflux. Clinical applications of the technique have increased with better knowledge of the protean clinical manifestations of gastro-oesophageal reflux disease, and include the evaluation of "typical" gastro-oesophageal reflux disease patients with negative endoscopy or refractory oesophagitis, the "atypical" manifestations of gastro-oesophageal reflux disease and the pre- and post-operative evaluation of patients undergoing antireflux surgery.
Calibration↗
Chest pain and gastro-oesophageal reflux.
Explore the source record for details and available documents.
Chest Pain↗
Monothematic meeting of the GISC.
Explore the source record for details and available documents.
Animals↗
A normal gastrointestinal motility excludes chronic intestinal pseudoobstruction in children.
Gastrointestinal manometry has gained wide acceptance in the approach to patients with suspected enteric neuromuscular disorders. However, performing gastrointestinal manometry in these subjects without a previous exhaustive diagnostic evaluation is unjustified. Twelve children (median age: 7.0 years; range: 8 months-13 years), with clinical and x-ray features suggesting chronic intestinal pseudoobstruction, were referred to our unit for gastrointestinal manometry. The latter was performed with a perfused catheter for 5 hr in the fasting state and for 90 min after feeding. Data were compared with those recorded in eight age-matched controls. In all patients and controls, interdigestive motor complexes with propagated phases III were detected; a regular postprandial antroduodenal motor activity was also recorded. Patients and controls did not differ for fed antral and duodenal motility indexes, fed antroduodenal coordination, and length of duodenal phase III. Most of the patients showed short or prolonged bursts of nonpropagated activity in the fasting and/or fed states; in four cases fasting and/or fed sustained phasic activity was recorded. Manometric evidence of migrating motor complexes and postfeeding activity did not support the diagnosis of intestinal pseudoobstruction and suggested redirecting the diagnostic evaluation. Final diagnoses were: Munchausen syndrome-by-proxy (four cases), celiac disease (two cases), intestinal malrotation (two cases), Crohn's disease (two cases), multiple food intolerance (one case), and congenital chloride-losing diarrhea (one case). It is concluded that in children with suspected chronic intestinal pseudoobstruction manometric evidence of migrating motor complexes and fed motor activity excludes an enteric neuromuscular disorder and suggests a reassessment of the diagnostic work-up. Furthermore, if gastrointestinal manometry shows migrating motor complexes and postfeeding motor activity, qualitative abnormalities of the manometric tracings do not indicate an underlying enteric neuromuscular disorder and must not be overemphasized. Patients referred for gastrointestinal manometry should previously undergo an extensive diagnostic investigation to exclude disorders mimicking chronic intestinal pseudoobstruction.
Adolescent↗
Combined segregation and linkage analysis of inflammatory bowel disease in the IBD1 region using severity to characterise Crohn's disease and ulcerative colitis. On behalf of the GISC.
Inflammatory bowel disease (IBD) is a chronic relapsing disorder affecting the gastro-intestinal tract and is subdivided into two main subtypes: Crohn's disease (CD) and ulcerative colitis (UC). Although the aetiology of IBD is unknown, a strong genetic susceptibility is suggested and different candidate regions have been identified for both CD and UC. The IBD1 region on chromosome 16 has been confirmed to be important for susceptibility to CD, whereas conflicting evidence has been obtained for UC. We performed a combined linkage and segregation analysis in the identified IBD1 region on a sample of 82 extended families with IBD using a parametric method implemented in the computer program COMDS. This approach allows simultaneous evaluation of linkage while estimating the mode of inheritance and to include severity of the trait to characterise the CD and UC phenotypes. Our results are consistent with the presence of a major gene in the IBD1 region close to D16S408 involved in both UC and CD. Furthermore, our data support evidence that a single mutation in the gene leads more frequently to UC, whereas inheritance of two mutant alleles results in the more severe CD. In our study the IBD1 locus was found to have a major role in IBD predisposition in the Italian population.
Adult↗