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  • 1
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  It is controversial whether CARD15 variants are truly associated with a more severe form of Crohn's disease. The relative role of CARD15 genotype and smoking in Crohn's disease progression is also debated.Aim:  To investigate the association between CARD15 variants and history of resective surgery in patients with Crohn's ileal disease, taking into account smoking as a possible confounding factor.Methods:  We originally assessed CARD15 genotype in 239 north Italian Crohn's disease patients (mean follow-up: 10.1 ± 8.1 years). We then focused on 193 patients with proven ileal involvement, 70 of whom (36.3%) carried CARD15-mutated alleles (G908R, R702W, L1007fs).Results:  Carriage of CARD15 variants was positively associated with family history and ileal-only disease and negatively associated with uncomplicated behaviour at maximal follow-up (P 〈 0.05). Ileal resection was the only variable independently associated with CARD15 variants at multivariate analysis (OR 3.8; 95% CI 1.6–9.2; P = 0.003). Kaplan–Meier analysis showed that ileal resection was favoured both by CARD15 variant-carriage (P = 0.01) and by smoking (P = 0.05), but smoking did not affect progression to surgery in variant carriers (P = 0.31). Thirteen of 14 (93%) patients being resection-free at 15-year follow-up, had CARD15 wild-type genotype (P = 0.01), whereas only seven (50%) had never smoked (P = 1.0).Conclusions:  In summary, CARD15 variant-associated Crohn's ileitis is virtually committed to stricturing and/or penetrating disease and, eventually, to resective surgery. Smoking accelerates progression to surgery in patients with wild-type CARD15 genotype, but it seems to exert no additional effect in CARD15-variant carriers.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Oral and topical mesalazine formulations are effective in active ulcerative colitis, but little is known on the efficacy of combined treatment.〈section xml:id="abs1-2"〉〈title type="main"〉Aim:To compare the efficacy of oral mesalazine vs. combined oral and topical mesalazine in mildly to moderately active ulcerative colitis.〈section xml:id="abs1-3"〉〈title type="main"〉Methods:Patients with mildly to moderately active ulcerative colitis (Clinical Activity Index, CAI 4–12) were identified at 15 participating centres. They were randomized to receive either mesalazine 4 g orally plus placebo enema, or mesalazine 2 g orally plus mesalazine 2 g rectally as a liquid enema for 6 weeks. The rate of clinical remission (CAI 〈 4) or clinical remission/improvement (reduction of CAI of 50% from baseline) at 6 weeks and time to clinical remission/improvement were primary end-points; the rate of endoscopic remission was a secondary end-point.〈section xml:id="abs1-4"〉〈title type="main"〉Results:67 patients were assigned to oral treatment and 63 to combined treatment. One patient in the oral group and 2 in the combined group discontinued the treatment due to adverse events. Following an intention-to-treat analysis, the rate of clinical remission was 82% for oral treatment and 87% for combined treatment (P=0.56); the mean time to remission 22.2 and 20.2 days, respectively (P=0.29); the rate of clinical remission/improvement and the rate of endoscopic remission were 85% and 91% (P=0.503) and 58% and 71% (P=0.21), respectively.〈section xml:id="abs1-5"〉〈title type="main"〉Conclusions:In patients with mild active ulcerative colitis, mesalazine 4 g orally and 2 g orally plus 2 g enema are equally effective in inducing disease remission.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Alimentary pharmacology & therapeutics 17 (2003), S. 0 
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The diagnostic work-up of ulcerative colitis at presentation is based on the collection of clinical, microbiological, radiological, endoscopic and histologic data. Serological markers are characterized by too low a sensitivity to be commonly utilized in clinical practice. Although endoscopic and histologic features are characterized by very high sensitivity and specificity for the diagnosis of ulcerative colitis, negative stool cultures and parasites are mandatory to exclude an infectious aetiology at presentation. The treatment of choice of an acute flare-up of distal ulcerative colitis is represented by oral or topical mesalazine, or a combination of both, whereas the use of topical or systemic steroids should be restricted to patients who prove to be refractory to first-line treatments. Preliminary data suggest that the achievement of endoscopic and histologic remission after an acute flare of the disease might be associated with a prolonged remission.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Alimentary pharmacology & therapeutics 20 (2004), S. 0 
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The goals of the Baveno workshops were to develop consensus definitions of key events related to portal hypertension and variceal bleeding, and to produce guidelines to facilitate the conduct and reporting of clinical trials. The consensus definitions concern the diagnosis of active bleeding, failure to control bleeding, the criteria to distinguish continuing bleeding from rebleeding, and the means of assessing failure to prevent rebleeding. The guidelines concern the timing of diagnostic endoscopy, the policy for blood volume restitution, the measures to prevent infection and encephalopathy, and the treatment options for acute bleeding, as well as primary and secondary prophylaxis. The intention of the experts who developed the guidelines was that, as feedback from their practical application develops, they should be adapted to better fit the practical needs. The applicability of the Baveno definitions has been evaluated in a study where the definitions of clinically significant bleeding, failure to control bleeding, the time frame for the acute bleeding episode and the definition of rebleeding were tested. The main criticism raised in this study was that tachycardia, one of the criteria that define failure to control bleeding, was misleading in 15% of patients who had the symptom but were not bleeding.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Journal of Chromatography A 52 (1970), S. 162-165 
    ISSN: 0021-9673
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Techniques in coloproctology 3 (1999), S. 185-188 
    ISSN: 1128-045X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    European journal of pediatrics 157 (1998), S. S67 
    ISSN: 1432-1076
    Keywords: Key words Homocystinura ; Cystathionine β-synthase ; Clinical variability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Homocystinuria due to cystathionine β-synthase (CBS) deficiency is an autosomal recessive disease of sulphur amino acid metabolism. Major clinical manifestations include disorders of the eye, the skeleton, the central nervous system and the vascular system. A wide clinical spectrum of the disease has been reported. We discuss the role of genetic factors (e.g. different mutations of the CBS gene and a variable genetic background) and the importance of environmental factors (e.g. diet, vitamins, perinatal factors and drugs) in explaining the phenotypic variability observed in homocystinuria. Conclusion Homocystinuria represents a good model to explain the clinical differences frequently observed among patients affected by monogenic diseases.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1573-2665
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Hyperhomocysteinaemia is an independent risk factor for cardiovascular disease. The C677T mutation of the methylenetetrahydrofolate reductase (MTHFR) is a common genetic cause of increased homocysteine (HCY) levels. Post-methionine-load HCY concentrations allow identification of certain cases of hyperhomocysteinaemia not demonstrated by fasting levels. This study investigated the relationship between MTHFR polymorphism and (1) fasting HCY levels (77 patients); (2) post-methionine HCY levels (54 patients); and (3) postprandial HCY concentrations (36 patients) in cardiovascular disease. As expected, mean fasting HCY value was higher in the +/+ patients. Moreover, patients who were homozygous for the mutation exhibited significantly increased mean post-methionine-load HCY; in contrast, literature results are conflicting. Mean postprandial HCY, which is not known to be increased in controls, was also increased in the (+/+) patients, although the difference did not reach statistical significance, probably owing to the small size of the sample. MTFHR polymorphism is known to be aggravated by a drop in circulating folate. Additional risk factors may be more prevalent in patients with cardiovascular disease.
    Type of Medium: Electronic Resource
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  • 9
    Publication Date: 2013-04-16
    Description: Previous studies indicated that a few risk variants for autoimmune diseases are subject to pathogen-driven selection. Nonetheless, the proportion of risk loci that has been targeted by pathogens and the type of infectious agent(s) that exerted the strongest pressure remain to be evaluated. We assessed whether different pathogens exerted a pressure on known Crohn's disease (CD) risk variants and demonstrate that these single-nucleotide polymorphisms (SNPs) are preferential targets of protozoa-driven selection ( P = 0.008). In particular, 19% of SNPs associated with CD have been subject to protozoa-driven selective pressure. Analysis of P values from genome-wide association studies (GWASs) and meta-analyses indicated that protozoan-selected SNPs display significantly stronger association with CD compared with nonselected variants. This same behavior was not observed for GWASs of other autoimmune diseases. Thus, we integrated selection signatures and meta-analysis results to prioritize five genic SNPs for replication in an Italian cohort. Three SNPs were significantly associated with CD risk, and combination with meta-analysis results yielded P values 〈 4 x 10 –6 . The bona fide risk alleles are located in ARHGEF2 , an interactor of NOD2, NSF , a gene involved in autophagy, and HEBP1 , encoding a possible mediator of inflammation. Pathway analysis indicated that ARHGEF2 and NSF participate in a molecular network, which also contains VAMP3 (previously associated to CD) and is centered around miR-31 (known to be disregulated in CD). Thus, we show that protozoa-driven selective pressure had a major role in shaping predisposition to CD. We next used this information for the identification of three bona fide novel susceptibility loci.
    Print ISSN: 0737-4038
    Electronic ISSN: 1537-1719
    Topics: Biology
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