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Longterm olsalazine treatment: pharmacokinetics, tolerance and effects on local eicosanoid formation in ulcerative colitis and Crohn's colitis.

To examine pharmacokinetics and tolerance of long term administration of olsalazine (azodisalicylate), increasing doses of the drug were given for one year to 31 patients with ulcerative colitis (UC) and nine patients with Crohn's colitis (CC), refractory to, or intolerant of sulphasalazine, until sustained remission was obtained or a maximum of 4 g/day was reached. Colonic drug metabolism was studied by equilibrium in vivo dialysis of faeces. Complete azoreduction occurred in most cases. Concentrations of 5-aminosalicylic acid, but not N-acetyl-5-aminosalicylic acid, in faecal dialysates increased dose dependently. Serum concentrations disclosed no cumulation in the long term and olsalazine was well tolerated, although loose stools occurred transiently in some patients with extensive disease: this was associated with a larger proportion of unsplit olsalazine in the faecal dialysates. Patients with ulcerative colitis having a high prostaglandin E2 concentration (greater than ng/ml) determined by equilibrium dialysis of rectum, were less likely to benefit from treatment. Olsalazine is a very effective means of delivery of 5-aminosalicylic acid to the colonic mucosa in active disease. Use of the drug in controlled trials may be considered safe even in prolonged high dosage.

Adolescent↗

Lymphocytic and collagenous colitis: the emerging entity of microscopic colitis. An update on pathophysiology, diagnosis and management.

Microscopic colitis (MC) encompasses the two morphologically distinct entities of collagenous colitis (CC) and lymphocytic colitis (LC). MC was first described less than 30 years ago but is presently recognized as a relatively common cause of chronic diarrhea in the adult population. Remarkably, up to 10% of adults who have a colonoscopy for the investigation of chronic diarrhea, and have endoscopically normal appearing mucosa, may have MC. Patients with MC generally present with chronic diarrhea, which can be associated with cramping and bloating. Endoscopic and radiological examinations are usually normal. Histological assessment reveals inflammation consisting predominantly of lymphocytic infiltration, and a thickened subepithelial collagen band is diagnostic of CC. Both LC and CC can be associated with autoimmune diseases such as celiac disease, diabetes, arthritis and thyroiditis, yet the mechanisms involved in the pathogenesis remain unclear. Emerging studies suggest that a stepwise approach be taken in the medical management of MC. This approach includes antidiarrheal agents and stopping of any offending agents; budesonide or bismuth subsalicylate; and cholestyramine or 5-acetylsalicylic acid agents. In resistant cases, oral corticosteroids and other immune modulatory therapy have been used.

Algorithms↗

New ulcerative colitis model induced by sulfhydryl blockers in rats and the effects of antiinflammatory drugs on the colitis.

We tried to produce a new ulcerative colitis model in rats by topical administration of sulfhydryl blockers. After male SD rats were fasted for 24 hr, 100 microliters of 3% N-ethylmaleimide (NEM) or iodoacetamide (IA) was introduced into the colon via a Nelaton's catheter. Both NEM and IA caused severe diarrhea with rectal bleeding and decreased body weight for about 7 days. At autopsy, adhesions and dilatation of the colon and severe mucosal lesions were observed. Both the weight and myeloperoxidase activity of the colon increased markedly. Maximum changes were observed within 1-3 days followed by gradual recovery, but even on day 21, some abnormalities were still observed. The ulceration and inflammation of the colon were confirmed by histological studies. Antiinflammatory drugs such as indomethacin inhibited the inflammation of the colon by NEM, but aggravated the ulceration. These results revealed that sulfhydryl blockers instilled into the colon caused ulcerative colitis in the rat. This model may be useful in studies on the pathogenesis of ulcerative colitis and the evaluation of drugs for therapy. Furthermore, it was suggested that antiinflammatory drugs may delay the healing of colonic ulcers.

Animals↗

[Ulcerative colitis or amebic colitis--a case report].

The large intestine reacts relatively monomorphically to different stimuli. From this differential-diagnostic problems may result. The history of a patient is described which could be pursued retrospectively and prospectively over 14 years and during the course of which the correction of the diagnosis ulcerous colitis into chronic relapsing amoebic colitis was necessary. As a conclusion is emphasized that in every symptomatology of colitis primarily bacterial and parasitologic examinations of the faeces should be brought about and it must be also thought of spontaneous amoebic infections in our country.

Animals↗

Sporadic hemorrhagic colitis associated with Escherichia coli, type O157:H7: unusual presentation mimicking ischemic colitis.

Hemorrhagic colitis is a bacterial infection of the colon, associated with a verotoxigenic strain of Escherichia coli, commonly serotype O157:H7. This recently described disease is usually self-limiting. Because fecal cultures are negative for the usual pathogens and the clinicopathologic features closely mimic ischemic colitis, the patient is exposed to the risk of unnecessary surgery. One such situation is described and differentiation between hemorrhagic and ischemic colitis is discussed.

Colitis↗

[Ulcerative rectocolitis: review of clinical characteristics in patients with distal colitis and extended colitis].

Ulcerative colitis is an inflammatory disease which, starting from the rectum, affects more or less extended tracts of the colon. Given that distal and extended forms are generally described as a single nosological entity, the authors aimed to verify whether there are any clinical differences between the two groups of patients with varying extents of disease. A retrospective review was made of data relating to 189 patients suffering from ulcerative colitis observed over a 90-months period. Only 111 cases were included in the study: all patients had undergone an endoscopic and histological diagnosis with a follow-up of over one year. Seventy-eight patients (41.26%) were excluded from the study because they had been lost during follow-up, or follow-up had lasted less than one year, or it had not been possible to perform pancolonoscopy. The 111 patients examined were subdivided into 2 groups: one (39 patients) with distal colitis, namely involving the rectum or recto-sigmoid, and the other (72 patients) with more extended disease. The extension of disease was evaluated on the basis of histological findings. The mean follow-up was 5 years and 11 months. The two groups were comparable for age, sex, number of annual attacks, maximum duration of disease-free periods, clinical evolution, predominant symptoms, extraintestinal symptoms and surgical treatment. Results were processed using Student's t test and the chi-square test.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Determination of the active moiety of BX661A, a new therapeutic agent for ulcerative colitis, by studying its therapeutic effects on ulcerative colitis induced by dextran sulfate sodium in rats.

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.

Alanine↗

Pseudomembranous colitis. A complication of sulfasalazine therapy in a patient with Crohn's colitis.

Pseudomembranous colitis is a potentially life-threatening acute medical problem usually associated with a history of previous antibiotic exposure. Presented here is a case of sulfasalazine associated pseudomembranous colitis in a patient with known Crohn's colitis. The diagnosis was confirmed by identifying Clostridium difficile toxin in the stool. This a newly reported complication of sulfasalazine therapy.

Adult↗

Salmonella colitis presenting as a segmental colitis resembling Crohn's disease.

Salmonella species have recently been shown to involve the colon in a diffuse fashion resembling ulcerative colitis by radiographic and endoscopic appearance. We describe a case of Salmonella colitis in which the radiographic and colonoscopic features were focal ulcerations, mucosal edema, friability, and a loss of normal vascularity, an appearance resembling Crohn's disease. This is the first well-documented example of this clinical presentation.

Colitis↗

The development of an elevated lesion associated with colitis cystica profunda in the transverse colonic mucosa during the course of ulcerative colitis: report of a case.

We report the case of a 53-year-old man with a long history of ulcerative colitis in whom an elevated lesion in the epithelium of the affected transverse colon was initially diagnosed as a benign inflammatory polyp by endoscopic biopsies. After 4 years of follow-up, because the tumor had enlarged and villous components were endoscopically observed on the surface, a colonic resection was performed. The tumor was found to consist of hyperplastic colonic epithelium associated with multiple mucinous cysts lined with dysplastic colonic epithelial cells. Moreover, the mucinous cysts were primarily located beneath the submucosal layer and appeared to intrude into the muscularis propria of the colonic wall. This lesion had a unique pathological feature, presumably indicating neither benign inflammatory epithelium nor a neoplastic lesion of the colonic epithelium. Mucinous cysts lined with colonic epithelial components in the muscularis propria suggest a loss of normal integrity of the colonic wall. Areas of the epithelial cell lining of the mucinous cysts showed apparent structural and nuclear atypia and positive expression for p53, suggesting that this portion of the specimen was dysplastic epithelium. These pathological findings may indicate one longitudinal aspect of tumor development which could provide evidence of premalignant change or initial pathological features during the long-standing course of ulcerative colitis.

Colitis↗

Observer variation of diagnoses based on simple biopsy criteria differentiating among Crohn's disease, ulcerative colitis, and other forms of colitis.

BACKGROUND AND AIM: Simple mucosal biopsy criteria proposed by authors reliably differentiate idiopathic inflammatory bowel disease (IBD) from other forms of colitis (non-IBD) and Crohn's disease involving the colon (CD) from ulcerative colitis (UC). The aim of this study is to investigate the reproducibility of these criteria. METHODS: Three established pathologists and two medical students blindly examined 20 sets of multiple biopsy slides from patients with CD, 20 from those with UC, and 20 from those with non-IBD. The students had been given instructions on histological definitions using another 15 sets previously. Each observer evaluated 10 histological items required in the criteria and determined categorical diagnoses such as definite IBD and probable UC. Interobserver agreement for the individual histological items was measured by using kappa analysis and Pearson's correlation, while it was measured for categorical diagnoses with the use of Spearman's rank correlation. RESULTS: All of the individual histological items expressed excellent or fair-to-good agreement among the five observers, although two items associated with the criteria for CD and UC had poor agreements among the students. With regard to categorical diagnoses based on the criteria for IBD and non-IBD, and those for CD and UC, coefficients for Spearman's rank correlation exceeded 0.92 and 0.86 among the pathologists, and 0.76 and 0.74 among the students, respectively; all of the coefficients were statistically significant (P < 0.05). CONCLUSIONS: The simple criteria were sufficiently reproducible and would help most pathologists to make an automated and objective diagnosis.

Biopsy↗

Simple mucosal biopsy criteria differentiating among Crohn disease, ulcerative colitis, and other forms of colitis: measurement of validity.

BACKGROUND: Recently established mucosal biopsy criteria reliably differentiate idiopathic inflammatory bowel disease (IBD) from other forms of colitis (non-IBD), and Crohn disease involving the colon (CD) from ulcerative colitis (UC) but were inconvenient in practical use because of the need for relatively complicated calculations. Our objectives were to establish simple criteria in which calculation could be done in the user's head and to measure their validity. METHODS: On the basis of the above original criteria, we constructed two sets of criteria in which coefficients and constants were simplified to integral numbers. The first set of criteria consisted of the diagnostic categories 'definite IBD', 'probable IBD', 'unknown', 'probable non-IBD', and 'definite non-IBD'. Similarly, the second set had five categories from 'definite CD' to 'definite UC'. The validity of the criteria was evaluated in 117 patients with CD, 125 with UC, and 484 with non-IBD. RESULTS: In categories of probable IBD and probable non-IBD both sensitivity and specificity exceeded 96.3%. Probable CD and probable UC showed sensitivities of 95.7% and 92.0% and specificities of 93.6% and 98.3%. CONCLUSIONS: Despite simplified coefficients and constants, the validity appeared to be high enough to apply the present criteria to routine work.

Adult↗

Surgical options in the treatment of ulcerative colitis and Crohn's colitis.

The surgical standard for ulcerative colitis was complete proctocolectomy. Colectomy with mucosal proctectomy reduces the problems of the perineal wound essentially. A conventional ileostomy can be avoided by Kock's pouch technique. Correct operative technique reduces the complications with necessary reoperation to 10-20%. A non-specific pouchitis will develop in 25% of the cases but can mostly be treated with metronidazol. Another option is reconstructive proctocolectomy with ileal reservoir with ileo-anal anastomosis. Its complications rate is about the same, patients integrity and satisfaction remarkably high. Although both techniques are demanding and should be restricted to specialized centers, there is nowadays no indication to amputation of the rectum for ulcerative colitis. An ileorectal anastomosis is an acceptable option under effective supervision of the retained mucosa because of the risk of cancer development. Conservative surgery with resection and reresection remains the therapeutic approach to Crohn's disease until etiology and causal therapy are known although surgery is not curative for Crohn's disease. 10 years recurrence rate is 30-50% and cannot be predicted or definitely influenced. Therefore removal of the rectum and permanent ileostomy should be avoided as long as possible. Pouch procedures are not indicated. Moderate resections and good general care avoid short bowel syndrome and deficiency disease.

Colectomy↗

[Ischemic-granulomatous colitis: a new differential diagnosis from Crohn's colitis?].

In patients with inflammatory bowel disease the presence of epitheloid cell granuloma is considered to be the most reliable single criterion for the presence of Crohn's disease. We report on 6 patients (5 female, 1 male, mean age 73.5 years) with acute onset of inflammatory bowel disease, in whom the presence of epitheloid cell granuloma led to the diagnosis of Crohn's disease. However, concomitant major bleeding (4/6), absence of small intestinal involvement, and absence of extraintestinal manifestations suggested the presence of ischemic colitis. Histologic findings including thrombosed vessels (6/6), mucosal (5/6) and submucosal (3/4) hemorrhage, and mucosal (3/6) and submucosal (3/4) fibrosis supported this diagnosis. A review of the literature suggests that many clinical features of assumed Crohn's disease in elderly patients are atypical and would be most consistent with an ischemic pathogenesis: rarity of fistula, low recurrence rate, low rate of small intestinal involvement and extra-intestinal manifestations, and increased incidence of major colonic bleeding would best fit with an ischemic pathogenesis in at least some of these patients. We suggest that in elderly patients with "Crohn's colitis", even in the presence of epitheloid cell granuloma, an ischemic etiology should be considered.

Age Factors↗

Sulfasalazine-induced colitis complicating idiopathic ulcerative colitis.

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.

Child↗

Acute colitis resembling ulcerative colitis in the hemolytic-uremic syndrome.

The case report of a 10-year-old boy, admitted to the hospital after he had experienced 4 days of periumbilical abdominal pain, intermittent vomiting, and diarrhea, is presented. He had proctoscopic and radiologic findings resembling ulcerative colitis. However, further analysis of laboratory data suggested hemolytic-uremic syndrome. Since the patient in the pediatric age group presents with a clinical picture mimicking ulcerative colitis, this hemolytic-uremic syndrome should be included in the differential diagnosis. Examination of a peripheral smear revealing typical findings of microangiogpathic, hemolytic anemia, thrombocytopenia, and a rising blood urea nitrogen value will lead to the diagnosis of hemolytic-uremic syndrome and early appropriate therapy.

Child↗

[Epithelial dysplasia in ulcerative colitis. Histological possibility for the early diagnosis of "colitis"-carcinoma (author's transl)].

From 249 histologically examined cases with ulcerative colitis (within the years 1967 to 1974) 20 cases were selected, which had an onset of the disease before the 20th year of age and/or a duration of more than 10 years. These cases were checked-up for "prae-cancerous" epithelial dysplasia. Four of these 20 cases showed medium to severe epithelial dysplasia together with carcinoma (= 1.61% of the entire collective). In 2 cases low grade to severe dysplasia occurred in different parts of the colon without demonstrable carcinoma. In 1 case epidermoid epithelial metaplasia were found in the splenic flexure and in the rectum. The biological significance of these metaplasia remains unclear. With reference to the formal pathogenesis these lesions are probably "indirect" metaplasia. The early diagnosis of "colitis"-carcinoma can be improved by systematic colonoscopic examinations resp. by colonoscopic biopsies. "Prae-cancerous" epithelial dysplasias, which occur in a high rate together with carcinoma, are found not only in the rectum but also in other parts of the colon. Multiple biopsies from different parts of the colon as well as the rectum would thus seem to be desirable if mucosal sampling is to be employed as a screening test.

Adult↗

Campylobacter colitis: a common infectious form of acute colitis.

A case of acute ulcerating colitis due to Campylobacter fetus is presented. The radiographic and endoscopic findings are indistinguishable from those of idiopathic acute ulcerative colitis. The clinical and bacteriological data relating to Campylobacter are discussed.

Adult↗