[Celiac colitis and ulcerative colitis].
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During the period from 1963 till 1981 altogether 342 patients suffering from ulcerative colitis were treated. In their material authors found 6 patients (1.7%) who achieved cancer of the colon beginning 7, 9, 14, 18, 18 und 21 years after the onset of ulcerative colitis symptoms. According to the clinical data their ulcerative colitis could be considered to belong to the severe or the moderate type. From the anatomical point of view the extension of the process exceeded the sigmoid colon in all but one. Respecting the clinical course of the disease, malignant transformation took place in 3 patients of the relapsing-remitting type, in 2 instances the clinical course could not be classified, the sixth case proved to the chronic continuous type. Colonic tissue was gained and diagnosis stated with traditional methods within 4 instances, while in 2 it was gained from tissue specimens passing through the stool. In 3 cases the tumour was multiple. From the morphological point of view the features had a plaque form in 2 cases, a polypous nature in other 2 cases, while among each one patient a fibrous stricture and ordinary colorectal cancer occurred. The tumour was identified as well differentiated and poorly differentiated adenocarcinoma in identically 3 instances. All the patients underwent an operation, only one of them is still alive. In sake of detecting colitis carcinoma earlier, they suggest yearly endoscopic and biopsy survey of ulcerative colitis patients.
Three patients with idiopathic ulcerative colitis and infection of Entamoeba histolytica were reviewed. They represented three different relationships between the two conditions, vis asymptomatic carrier, coexisting infection and superinfection causing exacerbation of colitis. A two-way relationship between amoebic colitis and ulcerative colitis has been discussed and the possible mechanisms in the literature have been reviewed. In patients with a short history of diarrhoea and in tropical countries where amoebic infection is endemic, it is important to role out amoebic colitis before commencing steroid therapy for inflammatory disease.
A diagnosis of idiopathic ulcerative colitis was made in a previously healthy 9-year-old boy. Symptoms persisted despite therapy with sulfasalazine, 50 mg/kg daily, but they eventually responded to treatment with parenteral nutrition and prednisone, 40 mg daily. Metronidazole was also given to eradicate persistent Dientamoeba fragilis from the stools. The symptoms resolved over 3 weeks, and the daily dose of prednisone was tapered. On two subsequent occasions a challenge with sulfasalazine caused an immediate recurrence of loose, blood-streaked stools and of nonspecific histologic features of ulcerative colitis, which resolved when the sulfasalazine was discontinued.
The subject of the study was in a trial of evaluation of selected behavioral patterns in patients with ulcerative colitis and acidpeptic disease of duodenum. As an evaluation method was employed the psychometric method consisting of the use of Nonconventional Adjectives Test the usefulness of which was confirmed in previous publications. The group of patients studied consisted of 65 persons with duodenal acid-peptic disease, 41 persons with ulcerative colitis and 72 healthy subject as a control group. The results obtained presented in a graphical manner reflected the psychological differences between above groups. Patients with ulcerative colitis were characterized by an increased fineness, sensibility or emotionality whereas those with duodenal acid-peptis disease selected adjectives indicating the lowered ability of self-control and of control on other people when compared with health subjects.
BACKGROUND: Ulcerative colitis is largely a disease of nonsmokers. Intermittent smokers often experience improvement in their symptoms while smoking. Nonsmokers with ulcerative colitis who begin smoking may go into remission. Randomized controlled trials were developed to test the efficacy of transdermal nicotine for the induction of remission in ulcerative colitis. OBJECTIVES: (1) To determine the efficacy of transdermal nicotine for induction of remission in ulcerative colitis. (2) To assess adverse events associated with transdermal nicotine therapy for ulcerative colitis SEARCH STRATEGY: The MEDLINE (via PubMed) and EMBASE databases were searched using the search criteria "ulcerative colitis" and "transdermal nicotine" or "nicotine" to identify relevant papers published between 1970 and December 2003. Manual searches of reference lists from potentially relevant papers were performed to identify additional studies. Abstracts from major gastroenterological meetings were searched to identify research submitted in abstract form only. The Cochrane Central Register of Controlled Trials and the Cochrane Inflammatory Bowel Disease Group Specialized Trials Register were also searched. SELECTION CRITERIA: We included only randomized controlled trials in which patients with active mild to moderate ulcerative colitis were randomly allocated to receive transdermal nicotine (15 to 25 mg/day) or a placebo or another treatment (corticosteroids or mesalamine). DATA COLLECTION AND ANALYSIS: Data extraction and assessment of the methodological quality of each trial were independently performed by each author. Any disagreement among reviewers was resolved by consensus. The primary outcome measure was the number of patients achieving clinical or sigmoidoscopic remission as defined by the primary studies (e.g. no symptoms of ulcerative colitis), and expressed as a percentage of the patients randomized (intention to treat analysis). Secondary outcomes included clinical response, adverse events and withdrawal because of adverse events. MAIN RESULTS: Seven studies were identified, five of which met the inclusion criteria. A meta-analysis of two trials in which 71 patients were randomized to nicotine and 70 to placebo showed a statistically significant benefit for nicotine treatment. After four to six weeks of treatment 19 of 71 patients treated with transdermal nicotine were in clinical remission compared to 9 of 70 treated with placebo (OR=2.56, 95% CI 1.02-6.45). In the same group of patients improvement or remission was noted in 29 of the 71 patients assigned to nicotine compared to 14 of 70 patients assigned to placebo (OR=2.72, 95% CI 1.28 - 5.81). For patients with left sided colitis the odds ratio was 2.31 (95% CI 1.05-5.10). When transdermal nicotine was compared to standard medical therapy no significant benefit for nicotine was observed. After four to six weeks of standard therapy (oral prednisone or mesalamine), 34 of 63 patients were in clinical or sigmoidoscopic remission compared to 33 of 66 patients treated with transdermal nicotine (OR=0.77, 95% CI 0.37-1.60). A meta-analysis of all five studies which included 137 patients treated with transdermal nicotine and 133 patients treated with a placebo or standard therapy demonstrated no statistically significant benefit of nicotine therapy (OR=1.23; 95% CI 0.71-2.14). Patients treated with transdermal nicotine were significantly more likely to withdrawal due to adverse events than patients treated with placebo or standard medical therapy (OR=5.82, 95% CI, 1.66 - 20.47) and were significantly more likely to suffer from an adverse event than patients treated with placebo or standard medical therapy (OR=3.54, 95% CI, 2.07 - 6.08). REVIEWERS' CONCLUSIONS: The results of this review provide evidence that transdermal nicotine is superior to placebo for the induction of remission in patient's with ulcerative colitis. The review did not identify any significant advantage for transdermal nicotine therapy compared to standard medical therapy. Adverse events associated with transdermal nicotine are significant and limit its use in some patients.
Oxazolone colitis (OC) is an experimental colitis that has a histologic resemblance to human ulcerative colitis. Here we show that IL-13 production is a significant pathologic factor in OC since its neutralization by IL-13Ralpha2-Fc administration prevents colitis. We further show that OC is mediated by NK-T cells since it can be induced neither in mice depleted of NK-T cells nor in mice that cannot present antigen to NK-T cells and mice lacking an NK-T cell-associated TCR. Finally, we show that NK-T cells are the source of the IL-13, since they produce IL-13 upon stimulation by alpha-galactosylceramide, an NK-T cell-specific antigen. These data thus describe a cellular mechanism underlying an experimental colitis that may explain the pathogenesis of ulcerative colitis.
BACKGROUND: Ulcerative colitis (UC) is characterized by a life-long chronic course with remissions and exacerbations. Approximately 15% of patients have a severe attack requiring hospitalization at some time during their illness. These patients are traditionally treated with intravenous corticosteroids, with a response rate of approximately 60%. The patients who do not respond to steroid treatment usually require surgical removal of the large bowel (proctocolectomy or colectomy with an anal pouch). This surgical procedure essentially cures the patient from the disease but is associated with complications such as pouchitis. Few alternative treatments exist for severe ulcerative colitis: immunosuppressive medications (such as azathioprine) have a slow onset of action and are therefore usually ineffective. Antibiotics are not proven to be effective and biological treatments such as infliximab are still under investigation. The introduction of cyclosporine-A (CsA) for use in patients with severe ulcerative colitis (UC) has provided an alternative to patients previously facing only surgical options. Cyclosporine acts mainly by inhibiting T lymphocyte function, which is essential for the propagation of inflammation. Unlike most other immunosuppressive agents, CsA does not suppress the activity of other hematopoietic cells, does not cause bone marrow suppression and has a rapid onset of action. This reviews aims to systematically assess the effectiveness and safety of CsA for severe UC. OBJECTIVES: This review aimed to evaluate the effectiveness of cyclosporine A for patients with severe ulcerative colitis. SEARCH STRATEGY: Electronic searches of The Cochrane Library (Issue 1, 2004), EMBASE (1980-2004), and MEDLINE (1966-2004); hand searching the references of all identified studies; contacting the first author of each included trial. SELECTION CRITERIA: Randomised clinical trials comparing cyclosporine A with placebo or no intervention to obtain and maintain remission of idiopathic ulcerative colitis. DATA COLLECTION AND ANALYSIS: Two reviewers independently appraised the quality of each trial and extracted the data from the included trials. Relative risks (RR) with 95% confidence intervals (CI) were estimated. The reviewers assumed an intention to treat analysis for the outcome measures. MAIN RESULTS: Only two randomized controlled trials were identified that satisfied the inclusion criteria. These two trials could not be pooled for analysis because of major differences in design and patient populations. In the first trial, 11 patients received intravenous cyclosporine (4 mg/kg) and 9 received placebo. Two of 11 in the treatment group failed to respond to therapy compared with nine of nine in the placebo group (RR 0.18, 95% CI 0.05 - 0.64). However, 3/11 and 4/9 eventually underwent colectomy in the treatment and placebo groups respectively and follow-up was less than a month. In the second trial 15 patients were treated with intravenous cyclosporine and 15 with intravenous methylprednisolone. Five of 15 patients in the cyclosporine group failed to respond to therapy as compared to 7/15 in the methylprednisolone group (RR 0.71, 95% CI 0.29 - 1.75). After 1 year 7/9 responders in the cyclosporine group were still in remission compared with 4/8 in the steroid group (p > 0.05) and the colectomy rate was similar in both groups. The mean time to response in the cyclosporine group in the 2 trials was short (7 days and 5.2 days). These results should be interpreted with caution given the small numbers of trials and patients evaluated for comparison, and limited follow-up (few weeks in one trial to a year in the other). The precise assessment of the occurrence of adverse events was difficult because the trials described different adverse reactions, which reversed after discontinuation of cyclosporine. There was no evidence in the trials reviewed that cyclosporine was more effective than standard treatment for preventing colectomy but this effect cannot be excluded due to the small sample size and rarity of this outcome. Additional limitations of current research include lack of data on quality of life, costs and long-term results of cyclosporine therapy. AUTHORS' CONCLUSIONS: There is limited evidence that cyclosporine is more effective than standard treatment alone for severe ulcerative colitis. The relatively quick response makes the short-term use of cyclosporine potentially attractive, but the long-term benefit is unclear, when adverse events such as cyclosporine-induced nephrotoxicity may become more obvious. There is a need for additional research on quality of life, costs and long-term results from cyclosporine therapy in severe ulcerative colitis.
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BACKGROUND: Ulcerative colitis is a condition of nonsmokers in which nicotine is of therapeutic benefit. AIMS: To examine the in vitro effect of nicotine on colonic smooth muscle activity and the role of nitric oxide (NO) as a mediator. METHODS: Nicotine, 1-10 microM, was administered to strips of circular muscle from the distal sigmoid colon of 9 patients with active ulcerative colitis and 18 with colorectal cancer. The effect of electrical field stimulation (EFS) was examined before nicotine was added. Finally L-NAME, a NO synthetase inhibitor, was added before nicotine was administered again. RESULTS: Muscle strips developed similar spontaneous resting tone. In response to EFS, ulcerative colitis tissue developed lower tensions than the controls. Nicotine significantly reduced the resting tone and peak tension after EFS, with a greater effect in controls. With L-NAME, peak tensions were increased more in ulcerative colitis than controls, and nicotine produced a much smaller reduction. CONCLUSIONS: Nicotine reduces circular muscle activity, predominantly through the release of nitric oxide-this appears to be 'up-regulated' in active ulcerative colitis. These findings may explain some of the therapeutic benefit from nicotine (and smoking) in ulcerative colitis and may account for the colonic motor dysfunction in active disease.
Ulcerative colitis is often accompanied by the development of extraintestinal, mainly articular, manifestations. Genetic differences could be underlying that clinical heterogeneity. We performed a case-control study to determine whether TNFab microsatellites or HLA-DR alleles were associated with the development of articular manifestations in patients with ulcerative colitis. With that aim, a total of 84 ulcerative colitis patients with articular manifestations and 172 without them were genotyped for TNFab microsatellites and HLA-DR. A healthy control sample (n = 595) was also included for comparative purposes. Haplotypes were inferred with the Arlequin software. The influence of HLA-DRB1*0103 and HLA-B27, factors previously known to be associated with extraintestinal manifestations, was specifically addressed. We observed that TNFa6b5 minihaplotype increases the susceptibility to developing articular manifestations in ulcerative colitis patients (p = 0.003, OR = 2.39). The locus HLA-DR does not appear to be involved in these extraintestinal manifestations by itself; however, the frequency of subjects carrying TNFa6b5 in combination with DR1, DR7, or DR11 is very significantly increased in patients with articular manifestations (p = 3.9 x 10(-8)). The associations found were independent of DRB1*0103 and HLA-B27. Thus, it seems that the development of articular manifestations in ulcerative colitis patients appears to be influenced by some genetic factor(s) present in some major histocompatibility complex haplotypes.
BACKGROUND: Ulcerative colitis begins in early childhood in 4% of cases. Medical therapy is non-specific, and as many as 70% of children will ultimately require surgery. The dynamic growth, physical and psychological changes that characterize childhood are severely compromised by the complications of ulcerative colitis and its therapy. OBJECTIVE: To review the outcome of children undergoing early surgery for ulcerative colitis at a tertiary medical center in Israel. METHODS: A retrospective review was conducted of all children operated on following failure of medical therapy for ulcerative colitis during a 5 year period. RESULTS: Eleven children underwent a J-pouch procedure with ileo-anal anastomosis in one to three stages. Postoperative complications included recurrent pouchitis in 5 patients, intestinal obstruction in 3, fistula with incontinence in one, stricture in one, and wound infection in 4. Follow-up revealed that most of the patients have three to four soft bowel movements daily. All currently enjoy normal physical activities and a rich social life. CONCLUSIONS: The quality of life in children with ulcerative colitis was markedly improved following J-pouch surgery. This procedure was not associated with major complications. We recommend early surgery as an alternative to aggressive medical therapy in children with this disease.
BACKGROUND: Ulcerative colitis is largely a disease of nonsmokers, and transdermal nicotine is of therapeutic value in the active disease. Because side effects are common, we developed a topical enema formulation of nicotine. OBJECTIVE: To study the pharmacokinetics of nicotine complexed with a polyacrylic carbomer and administered by enema to eight healthy volunteers and to eight patients with active ulcerative colitis, verified sigmoidoscopically. PATIENTS AND METHODS: All 16 subjects were nonsmokers. The mean age for normal subjects was 33 years; the mean for patients with ulcerative colitis was 60 years. Median stool frequency for patients with ulcerative colitis was four daily. Patients were taking 5-amino salicylic acid compounds and five were taking oral prednisolone (median dose, 12 mg daily). Nicotine, 6 mg, complexed with carbomer 974P, 400 mg, was administered in a 100 ml enema after an overnight fast, with serial blood measurements taken over 8 hours. Serum nicotine and cotinine were measured by gas liquid chromatography. Area under the concentration-time curves were calculated by the trapezoidal method, and the terminal elimination half-life was derived by extrapolation of the log-linear terminal phase. RESULTS: With the exception of nicotine time to reach peak concentration, which was longer in patients (median of 60 minutes compared with 45 minutes; p < 0.005), other comparisons between normal subjects and patients showed no statistically significant difference, although there was considerable inter-subject variation. Maximum concentration of nicotine, 8.1 +/- 3.5 ng/ml, in the 16 subjects occurred after a median of 60 minutes (range, 30 to 180 minutes); maximum cotinine concentrations of 60.4 +/- 11.5 ng/ml occurred after 4 hours. Side effects in five subjects were mild (four subjects) or moderate (one subject) and included lightheadedness, nausea, and headache; these five subjects were female lifelong nonsmokers of low body weight. CONCLUSION: Because most of the active ingredient of nicotine is converted to continine on the first pass through the liver, substantial concentrations can be achieved at the site of disease with only modest rises in serum nicotine, which are responsible for side effects; cotinine has low pharmacologic activity. Topical administration of nicotine may be useful treatment for distal ulcerative colitis.
5-[4-(2-Carboxyethylcarbamoyl)phenylazo]salicylic acid disodium salt dihydrate (CAS 80573-04-2, BX661A) is being developed as a therapeutic drug for ulcerative colitis. To determine the active therapeutic moiety of BX661A, the therapeutic effects with single and combined administration of 5-aminosalicylic acid (5-ASA), 4-aminobenzoyl-beta-alanine (4-ABA) and 4-amino-N-2-pyridinyl-benzenesulfonamide (CAS 144-83-2, sulfapyridine, SP) on ulcerative colitis induced by dextran sulfate sodium (DSS) in rats were investigated, and the following results were obtained. 1. BX661A at doses of 30, 100 and 300 mg/kg (p.o.) dose-dependently decreased the erosion area (mm2) in the large intestine with % inhibition values of 28.7, 49.1 and 61.6%, and the shortening of the large intestine with % inhibition values of 17.1, 25.7 and 48.6%, respectively. Salazosulfapyridine (SASP) at doses of 30 and 100 mg/kg (p.o.) decreased the erosion area (mm2) in the large intestine with % inhibition values of 30.7 and 45.3%, respectively, but did not improve the shortening of the large intestine. However, at a dose of 300 mg/kg (p.o.) SASP, the % inhibition value of the erosion area in the large intestine was reduced. 2. A single intrarectal administration of 5-ASA (105 mg/kg, i.r.) significantly decreased the erosion area (mm2) in the large intestine, but a single administration of 4-ABA or SP did not show any significant effect on the erosion area. Combined administration with 5-ASA (105 mg/kg, i.r.) and 4-ABA (142.8 mg/kg, i.r.) significantly decreased the erosion area (mm2) in the large intestine with a % inhibition value of 63.8%. On the other hand, the efficacy of 5-ASA disappeared with combined administration with SP (% inhibition value of 7.3%). These results suggest that 5-ASA is the active moiety for the therapeutic effects of BX661A and indicate that the efficacy of 5-ASA disappears with the combined use of SP, but not of 4-ABA. Therefore, it seems that BX661A is clinically safe and more effective than SASP in the treatment of patients with ulcerative colitis.
BACKGROUND & AIMS: Leukotriene B4 is a major neutrophil chemoattractant detected during relapse of inflammatory bowel disease and represents a potentional therapeutic target. The aim of this study was to compare the efficacy of zileuton, an active 5-lipoxygenase inhibitor, with mesalazine and placebo in the maintenance of remission in ulcerative colitis. METHODS: A double-blind, parallel-group, multicenter, and multinational trial was conducted during a 6-month period in hospital-based patients with inflammatory bowel disease. Three hundred five evaluable patients with ulcerative colitis in remission at the start of the trial were randomized into groups to undergo oral treatment with zileuton (600 mg qid; n = 113), mesalazine (400 mg qid; n = 99), or placebo (n = 111). The primary efficacy outcome was maintenance of remission for 6 months. A multivariate analysis was used to investigate determinants of relapse. Safety was assessed by treatment discontinuation, adverse events, vital signs, and laboratory parameters. RESULTS: After 6 months, 54% of patients receiving zileuton remained in remission compared with 43% receiving placebo (P = 0.094) and 63% on mesalazine (P = 0.266). Relapse rates on mesalazine were significantly lower than those for placebo (P = 0.017). All treatments were well tolerated. CONCLUSIONS: Zileuton (600 mg qid) was not significantly better than placebo in the maintenance of remission of ulcerative colitis in this trial and may have limited potential in the treatment of this condition.
BACKGROUND: Ulcerative colitis is largely a disease of nonsmokers. Because anecdotal reports suggest that smoking and nicotine may improve the symptoms of the disease, we examined the effect of nicotine as a supplemental treatment for ulcerative colitis. METHODS: We treated 72 patients with active ulcerative colitis with either transdermal nicotine patches or placebo patches for six weeks in a randomized, double-blind study. Incremental doses of nicotine were given; most patients tolerated doses of 15 to 25 mg per 24 hours. All the patients had been taking mesalamine, and 12 were receiving low doses of glucocorticoids; these medications were continued without change during the study. Clinical, sigmoidoscopic, and histologic assessments were made at base line and at the end of the study; symptoms were recorded daily on a diary card, and the clinician made a global assessment. Side effects and plasma nicotine and cotinine concentrations were monitored throughout the study. RESULTS: 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). CONCLUSIONS: The addition of transdermal nicotine to conventional maintenance therapy improves symptoms in patients with ulcerative colitis.