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A relapse was observed in most cases within 3 years, and in all recruited patients within a space of ten years. The extent of the disease in the colon is an important prognostic factor, as patients with distal colitis showed a lesser tendency to relapse.
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In HCT116, 5-ASA reduced the mutant fraction at (CA)13 by 48.3%, at A10 by 35.6-43.6%, at G10 by 74.9-83.6%, and at (AAAG)17 by 37.6-44.4%. Similar results were observed in hMLH1-proficient HCT116+chr3 cells. Moreover, the presence of 5-ASA significantly reduced mutations in TGFBR2 (A10) and ACVR2 (A8) by 39.9% and 46.2%, respectively.
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Release profile of time-dependent DS coated tablets was not influenced by pH of the dissolution medium, but the lag time of DS release was primarily controlled by the thickness of the coating layer. The thicker the coating layer, the longer the lag time of DS release is. On the contrary, in view of the pH-dependent 5-ASA coated pellets, 5-ASA release was significantly governed by pH. Moreover, the 5-ASA release features from the coated pellets depended upon both the combination ratio of the Eudragit L100 and S100 pH-sensitive copolymers in the coating formulation and the thickness of the coating layer. The absorption kinetic studies of the DS coated tablets in dogs demonstrated that in vivo lag time of absorption was in a good agreement with in vitro lag time of release.
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The aim of this randomized controlled study was to investigate the efficacy of ciprofloxacin compared with mesalazine in treating active Crohn's disease.
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Studies were accepted for analysis if they were randomized controlled clinical trials of parallel design, with a minimum treatment duration of four weeks. Studies of oral 5-ASA therapy for treatment of patients with active ulcerative colitis compared with placebo, SASP or other formulations of 5-ASA were considered for inclusion. Studies that compared once daily 5-ASA treatment with conventional dosing of 5-ASA (two or three times daily) and 5-ASA dose ranging studies were also considered for inclusion.
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Monitoring thiopurine metabolites can assist physicians in optimizing 6-MP and AZA therapy in treating patients with IBD. Of the dosing strategies reviewed, we found evidence for monitoring thiopurine metabolite level, use of allopurinol with thiopurine, use of mesalamine with thiopurine, combination therapy with thiopurine and anti-tumor necrosis factor agents, and split dosing of AZA or 6-MP to optimize thiopurine therapy and minimize adverse effects in IBD.
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Ulcerative colitis (UC) may have diverse extraintestinal manifestations. Nutritional deficiencies, medications or immune-mediated epiphenomena are considered to be pathogenic mechanisms involved. We describe a case of a 56-year-old woman who presented with rapidly progressive tingling paraesthesias in both lower limbs followed by sensory ataxia, ascending spastic quadriparesis, urgency and urge incontinence of 3 months duration. She had an episode of bloody diarrhoea 1 month later for which a colonoscopy was carried out with colonic biopsy features revealing a diagnosis of UC. In view of lack of alternative aetiology, the posterolateral column disease in our patient was attributed to an extraintestinal manifestation of UC. She improved dramatically with a course of intravenous steroids followed by tapering dose of oral steroids and oral mesalamine for her UC. Although rare, UC should be considered in the differential diagnosis of posterolateral column disease of the spinal cord in the appropriate clinical scenario.
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A series of novel ATB-429 (an anti-inflammatory candidate) derivatives containing a nitric oxide (NO)-releasing moiety were designed, synthesized and evaluated for their in vitro activity against six human cancer cell lines. Our results reveal that phenylsulfonylfuroxan-based derivatives have considerable antitumor activity, and compounds 7-9 (IC50s: 0.256-3.024 μM) against HT-29 and PANC-1, 8a,b (IC50s: 2.677-3.051 μM) against MCF-7 and 8a (IC50: 1.270 μM) against DU145 are more active than Vandetanib (IC50s: 1.925-4.107 μM).
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Electronic searches of the MEDLINE database (1966-2008), the Cochrane Central Register of Controlled Trials and the Cochrane IBD/FBD Group Specialized Trials Register were supplemented by manual reviews of reference listings and conference proceedings.
More than two-thirds of ulcerative colitis patients experience at least one relapse over a period of 10 years. Treatments that reduce the likelihood of relapses also reduce the risk of long-term complications.
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A 66-year-old male developed lymphocytic alveolitis with bronchiolitis after 3 month's treatment with mesalazin for ulcerative colitis. The patient's symptoms disappeared after halting mesalazin and increasing the steroid dose, the reduced diffusing capacity ameliorated and the thoracic X-ray normalized. The question whether this was a case of pulmonary involvement in inflammatory bowel disease or a drug side effect.
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Mesalazine is a first-line drug in pediatric inflammatory bowel disease, and is effective as primary treatment and maintenance therapy. It's usually well tolerated, but various side effects have been described. A 15-year-old female with ulcerative colitis developed polyuria, polydipsia, vomiting, and fatigue. She was receiving mesalazine (500 mg, thrice daily, p.o.) and prednisolone for 4 months. She was detected as acute tubular injury as she had dehydration, acidosis, hypostenuria, hematuria, proteinuria, low levels of potassium, uric acid and bicarbonate. These findings were attributed to interstitial nephritis as a side effect of mesalazine, however as renal biopsy was disapproved by the parents, it was not confirmed. After discontinuation of mesalazine her renal tubular functions improved. Potassium and phosphorus supplements were stopped after 7 months, although she had to continue bicarbonate supplementation. We conclude that regular renal screening is important in patients receiving 5-ASA therapy to prevent rare but serious complications, such as interstitial nephritis sometimes leading to chronic renal failure.
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We found 13 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
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To assess the frequency and determinants of 5-ASA use in CD patients and to evaluate the physicians' perception of clinical response and side effects to 5-ASA.
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Seventeen of the 35 patients in the nicotine group had complete remissions, as compared with 9 of the 37 patients in the placebo group (P = 0.03). The patients in the nicotine group had greater improvement in the global clinical grade of colitis (P < 0.001) and the histologic grade (P = 0.03), lower stool frequency (a difference of 1.6 stools daily; P = 0.008), less abdominal pain (P = 0.05), and less fecal urgency (P = 0.009). More patients in the nicotine group had side effects (23, vs. 11 in the placebo group; P = 0.002), the most common of which were nausea, lightheadedness, headache, and sleep disturbance. Withdrawals due to ineffective therapy were more common in the placebo group (3 vs. 8, P = 0.12).
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A dextran sodium sulfate/azoxymethane-induced mouse colon cancer model was used, and the chemopreventive effects of 5-ASA and PPARgamma ligands, given in the remission phase of colitis, against colitis-related colon carcinogenesis, were evaluated.
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We conducted a Danish cohort study based on data from a population based prescription registry, the Danish Birth Registry, and the Hospital Discharge Registry in North Jutland County.
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Mean age of the subjects was 42.2 years, and the mean follow-up period was 4.7 years. In univariate analysis, the use of infliximab in group B was significantly higher than group A (4.5% vs. 7.6%, p=0.016), and UC-related hospitalization (45.8% vs. 40.1%, p=0.031) and UC-related surgery (6.4% vs. 3.5%, p=0.010) in group B was significantly lower than that of group A. The use of oral steroid in surgery group was significantly higher than non-surgery group in multivariate analysis (OR 1.85, 95% CI 1.03-3.30, p=0.039).
To determine the pharmacokinetic parameters of 5-aminosalicylic acid and N-acetyl-5-aminosalicylic acid from equimolar doses of 5-aminosalicylic acid administered as Asacol and balsalazide.
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We retrospectively and prospectively analyzed the efficacy of pH-5-ASA in mildly to moderately active UC patients in whom time-5-ASA did not successfully induce or maintain remission. The clinical efficacy of pH-5-ASA was assessed by clinical activity index (CAI) before and after switching from time-5-ASA. In addition, the efficacy of pH-5-ASA on mucosal healing (MH) was evaluated in a prospective manner by measuring fecal calprotectin concentration.
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We evaluated the usefulness of various parameters in predicting the prognosis of ulcerative colitis. The records of 73 patients with ulcerative colitis were examined retrospectively. Patients were divided into two groups according to whether they had received only 5-aminosalicylic acid (5-ASA; n = 26) or glucocorticoids and/or azathioprine with or without 5-ASA (n = 47). The disease extent, endoscopic activity and ulcerative colitis activity index (UCAI) before therapy were recorded, together with the disease outcome. No statistically significant differences in outcome were observed in relation to therapy group, disease extent or endoscopic activity. UCAI had a significant effect on outcome, however: patients with lower UCAI values were more likely to remain in remission and less likely to require urgent surgery or experience a fatal outcome than those with higher UCAI values. This difference was apparent in both treatment groups. Thus a high pre-treatment UCAI may indicate a worse outcome.
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IBD often affects patients during their peak reproductive years. Several drugs are available for the treatment of IBD and new drugs are continuously in the pipeline. As long-term administration of medications is often necessary, the safety of drug therapy during pregnancy and breast-feeding needs to be considered in daily clinical practice. The aim of this Review is to summarize the latest information concerning the safety of medications used to treat IBD during pregnancy and lactation, as well as their effect on fertility. Although only thalidomide and methotrexate are absolutely contraindicated during pregnancy and breast-feeding, alternatives to ciprofloxacin, natalizumab and sodium phosphate should also be considered for pregnant women. Breast-feeding is also discouraged while on treatment with ciclosporin, metronidazole and ciprofloxacin. However, therapy with 5-aminosalicylic acid preparations, glucocorticoids, thiopurines and TNF inhibitors are acceptable during pregnancy and lactation. Pregnant women who have symptomatic IBD or who require therapy should have the opportunity to discuss any associated risks to their pregnancy and infant with the appropriate consultants. By ensuring that the patient and her family are informed, the clinical outcome might be optimized.
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In this cohort of pediatric patients, LC was much more common than CC. As described in adults, we observed associations with celiac disease, type 1 diabetes mellitus, and medications; we additionally saw an association with immunodeficiency. Our patients showed greater response to steroids than mesalamine or bismuth.
A multicentre randomized controlled trial was conducted to evaluate the efficacy of oral mesalazine (5-aminosalicylic acid) for the prevention of post-operative recurrence in 110 patients operated on for Crohn's disease by first intestinal resection. Patients were randomly allocated to receive 2.4 g/day of mesalazine, or no treatment at all. The protocol included colonoscopy with ileoscopy at 6 months and yearly thereafter. Recurrence was defined on the basis of endoscopic criteria and classified as mild or severe.
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Three hundred and seventy-nine individuals were enrolled in the study (93 treated with 5-aminosalicylates, 91 with azathioprine, 70 with infliximab, 43 with combined treatment with infliximab and azathioprine, and 82 controls). More than 90% of the patients had previous EBV exposure. EBV DNA was found in 132 samples (35%); its prevalence was significantly higher in every group of patients with IBD, comparing to controls. Among patients with IBD, infliximab with or without azathioprine was related to higher prevalence of EBV comparing to azathioprine alone or 5-aminosalicylates (P < 0.05). Age above 60 years was related to EBV DNA positivity with a specificity of 92%. Concerning treated groups, ulcerative colitis was the only risk factor identified for high levels of EBV DNA (>1000 and 2500 copies per milliliter). No relationship was found between EBV and C-reactive protein.