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PubMed1993

Red blood cell folate is associated with the development of dysplasia and cancer in ulcerative colitis.

Patients with extensive ulcerative colitis have a high risk of developing colon cancer. The etiology of mucosal dysplasia, a premalignant lesion that is used as a screening test in surveillance programs, is unknown. Previously, a case-control study [Lashner et al. (1989) Gastroenterology 97:255-259] suggested that folate supplementation was associated with a 62% reduction in the risk of developing dysplasia or cancer. The current case-control study was performed to obtain a better definition of this risk. All 67 patients with chronic ulcerative pancolitis having surveillance colonoscopy during a 1-year period were entered. There were 6 cases (4 with dysplasia and 2 with cancer) and 61 controls (no cancer or dysplasia). Red blood cell folate, reflecting intermediate-term stores, was a mean of 66.2 ng/ml lower in cases compared to controls. Serum folate, reflecting short-term stores, was not different between groups. Adjusting for confounding effects of age, sex, race, disease duration, and folate supplementation, the risk of dysplasia or cancer was significantly decreased by 18% for each 10 ng/ml increase in red blood cell folate (odds ratio 0.82, 95% confidence interval 0.68-0.99). Vitamins A, D, and E and carotene were lower in cases than in controls, but no water-soluble vitamin other than red blood cell folate was associated with an increased cancer risk. Depressed red blood cell folate is associated with an increased risk of dysplasia and cancer in patients with ulcerative colitis and may be a risk factor for neoplastic transformation.

Adult↗
PubMed1978

Endoscopic studies on the minute structures of colonic mucosa in the follow-up observation of ulcerative colitis.

Thirty cases of ulcerative colitis were examined endoscopically by means of magnifying colonoscope with dye spraying method (the combined method), and their minute mucosal structures were classified into four categories endoscopically, which correlated well with the histological findings. By this procedure, it was easy to detect the subsidence of inflammation of the mucosa in the quiescent phase or to reveal the active inflammatory involvement of the bowel. Moreover, inspecting the minute changes of the colonic mucosa detected by the combined method, remission was more correctly decided and rigid control is contributing to the decrease in the recent rate of recurrence of ulcerative colitis.

Adolescent↗
PubMed1980

Bronchial disease in ulcerative colitis.

Ten patients with ulcerative colitis, all of whom were non-smokers, presented with a productive cough. In six, the chest radiography was normal and cough was the only symptom; three of these patients had a minor obstructive ventilatory defect on testing. Four patients complained of exertional dyspnoea and had both an abnormal chest radiograph with bilateral pulmonary shadows and a mixed obstructive and restrictive ventilatory defect. Bronchial epithelial biopsies from four patients (two with and two without pulmonary shadows) revealed basal reserve cell hyperplasia, basement membrane thickening, and submucosal inflammation, changes more usually associated with cigarette smoking. Inhaled beclomethasone diproprionate relieved cough in seven patients. The occurrence of airway epithelial disease in association with ulcerative colitis raises the possibility of a systemic mechanism affecting both bronchial and colonic epithelium. It does not seem likely that sulphasalazine was the cause of the pulmonary syndrome in these subjects.

Adult↗
PubMed1980

Increased incidence of faecal coliforms with in vitro adhesive and invasive properties in patients with ulcerative colitis.

Faecal samples were collected from 23 patients with active ulcerative colitis, 15 patients with established ulcerative colitis in remission, 20 patients with active colitis of cause other than ulcerative colitis, and 20 normal control subjects. Ten coliform colonies were randomly selected from the faecal sample cultures and serotyped before the testing of each different serotype from each sample for adhesive or invasive properties on HeLa cell monolayers. In the patients with both active ulcerative colitis and ulcerative colitis in remission and those with other types of colitis one serotype tended to dominate the faecal coliform flora. In normal controls more variety was encountered. Thirty-five per cent of the patients with active ulcerative colitis and 27% of the patients with ulcerative colitis in remission had at least one adhesive or invasive faecal coliform as compared with 5% of the patients with other types of colitis and 5% of the normal controls. These findings are significant (P < 0.05) and may have aetiological and therapeutic significance.

Adhesiveness↗
PubMed2003

Effect of oral tacrolimus (FK 506) on steroid-refractory moderate/severe ulcerative colitis.

BACKGROUND: Steroid refractory ulcerative colitis is most commonly treated with intravenous ciclosporin to avoid colectomy. In search for an alternative drug that can be administered orally we investigated oral tacrolimus (FK 506) for this indication. METHODS: Nine patients with active, moderate/severe steroid refractory UC were treated with oral tacrolimus with a daily dose of 0.15 mg/kg body weight. After patients had responded azathioprine was added for long-term immunosuppression. RESULTS: All patients responded within 1-2 weeks. After 12 weeks of tacrolimus therapy six patients (67%) were in complete remission, two patients (22%) had mild to moderate disease activity, and one patient (11%) underwent colectomy. After a mean follow up of 21 months six of the nine patients (67%) had their colon in situ. Two patients developed severe side-effects, one thrombopenia with intestinal bleeding, and one bicytopenia. Mild side-effects were common. CONCLUSION: Oral tacrolimus may be an effective alternative to intravenous ciclosporin for the therapy of steroid-refractory ulcerative colitis. Patients receiving tacrolimus need to be watched carefully for side-effects.

Administration, Oral↗
PubMed1991

The presence in experimental animals of a colon specific Mr 40,000 protein(s) with relevance to ulcerative colitis.

In patients with ulcerative colitis a colon tissue bound IgG and serum antibodies against an Mr 40,000 colonic protein(s) has been identified. Using an anti-Mr 40,000 protein monoclonal antibody, 7E12H12, by an immunocytochemical method, the protein was localised in human tissue exclusively to colonic epithelial cells. In this study the presence of the Mr 40,000 protein was assessed in experimental animals by the direct and inhibition enzyme linked immunosorbent assays (ELISAs) using the anti-Mr 40,000 protein monoclonal antibody, 7E12H12 (IgM isotype). In addition, a total of 129 specimens including colon, small intestine, gall bladder, biliary tract, and kidney from nine strains of rats and mice, and from human tissue were studied by the immunocytochemical method using 7E12H12. All colon specimens from both humans and animals reacted with 7E12H12 in the immunocytochemical and ELISA assays. None of the non-colonic organs reacted with 7E12H12. While in human colon 7E12H12 recognised the absorptive epithelial cells, in all the animals it recognised mainly the colonic goblet cells. Extracts of animal colon but not of small intestine inhibited the binding of 7E12H12 to the human colon extract. This study shows the presence of an organ specific Mr 40,000 colonic epithelial protein(s) in humans and experimental animals. A differing cellular localisation of the Mr 40,000 protein(s) in human v animal tissue was also shown. Further characterisation of the Mr 40,000 protein(s) may provide important clues regarding the autoimmune mechanisms in ulcerative colitis.

Animals↗
PubMed1992

Acetic acid-induced colitis in the rat: a reproducible experimental model for acute ulcerative colitis.

There exists no ideal model for experimental ulcerative colitis in common laboratory animals. Therefore, we tried in the present study to establish a reproducible model for inducing colitis in rats by using acetic acid. A blind loop of the colon including the cecum, ascending colon and part of the transverse colon, was brought out through two colostomies. After mechanical washing with warm normal saline, acetic acid was instilled at different doses (4, 6 and 8%) for different exposure times (10, 15, 20, 25 and 30 s). The excluded colon was examined by light microscopy on the 1st, 2nd, 3rd, 4th, 7th and 14th days after operation and acetic acid instillation. We found that 4% acetic acid for 15 s produced a moderate, superficial colitis on the 1st day after operation, whereafter a uniform colitis evolved in all rats on the 4th day after operation. The developed colitis showed morphological similarities with human ulcerative colitis. Signs of healing and regeneration of the mucosa were seen on the 7th day, and the mucosa became almost normal at the 14th day after operation. 6 or 8% acetic acid solution or exposure times exceeding 15 s resulted in severe, deep colitis with a concomitant high mortality rate. In contrast, at exposure times less than 15 s, acetic acid induced only mild superficial colitis. We conclude that by using 4% acetic acid for 15 s in the excluded colon a uniform and reproducible colitis pathologically resembling human ulcerative colitis could be achieved. Furthermore, no mortality was encountered and the general health of the rats was similar to that of the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗
PubMed1999

[Bronchiectasis in a patient with ulcerative colitis].

Bronchopulmonary involvement is uncommon in ulcerative colitis. Bronchiectasis is a rare manifestation of the disease. We report a case of a 65-year-old patient with ulcerative colitis in whom we diagnosed bronchiectasis. The evidence of a relationship between bronchiectasis and ulcerative colitis was established on the basis of 3 criteria: the late occurrence of bronchiectasis in a patient without pulmonary history, their appearance after the ulcerative colitis developed and their improvement after inhaled corticosteroid treatment. This observation points out that ulcerative colitis investigations should be extended to the respiratory structures. The respiratory involvement is not always concomitant with the bowel disease. This observation suggests the efficiency of the inhaled corticosteroids in this disease.

Aged↗
PubMed2005

Oral methotrexate in ulcerative colitis.

BACKGROUND: We performed an audit of methotrexate for ulcerative colitis, because efficacy is unclear. Aim : To investigate the role of methotrexate in the management of ulcerative colitis. METHODS: Patients with ulcerative colitis treated with oral methotrexate at the inflammatory bowel disease clinics of Oxford and Wycombe General Hospital, UK, were evaluated. Efficacy was defined by remission (complete steroid withdrawal for >3 months) and response (good, partial or nil, proportionate reduction of steroids). RESULTS: There were 50 patients (42 ulcerative colitis alone; eight had rheumatoid arthritis associated with ulcerative colitis and were analysed separately). Indications for methotrexate in ulcerative colitis alone were azathioprine intolerance (31 of 42) and lack of benefit from azathioprine (11 of 42). The mean dose of methotrexate in ulcerative colitis alone was 19.9 mg/week for a median of 30 weeks (range: 7-395). Remission occurred in 42%. The response was good in 54% and partial in 18%. Side-effects occurred in 23%; 10% stopped treatment because of side-effects. Of those treated with methotrexate because of treatment failure with azathioprine, three of 11 achieved remission, but four came to colectomy within 90 days of starting methotrexate. The colitis remained in remission in seven of eight of those with RA treated with methotrexate and ulcerative colitis (mean dose 15.0 mg/week). CONCLUSION: Oral methotrexate (approximately 20 mg/week) is well-tolerated and moderately effective in steroid-dependent or steroid-refractory patients with ulcerative colitis.

Adolescent↗
PubMed1998

Steroid complications and surgery in intractable ulcerative colitis.

The major operative indication for ulcerative colitis is intractability. Although steroid side effects appear to be closely associated with surgical indications for intractable ulcerative colitis, this relationship has yet to be analyzed in detail. To elucidate this relationship, we investigated 39 surgical patients with intractable ulcerative colitis, as defined by the Research Committee for Intractable Diseases of the Ministry of Health and welfare of Japan, and 66 conservatively treated patients with ulcerative colitis, of whom 6 had intractable disease. All patients with major steroid side effects and 17/24 (71%) patients with minor side effects underwent surgery. The median number of admissions was higher in patients with major side effects than in those with less severe or no side effects in the operative series, while this value was lower in the non-operative series than in the operative series. This tendency was similar for the total duration of hospitalization and the number of relapses. In the operative series, markedly higher steroid doses were administered to patients with side effects than to those without, and lower doses were given in the non-operative series. On multivariate regression analysis, the presence of steroid side effects, disease extent, and disease duration were significantly associated with surgery. Patients without side effects had a higher postoperative complication rate than those with minor side effects. We conclude that major side effects are a surgical indication for patients with intractable ulcerative colitis, and that even minor side effects should be taken as a surgical indication in view of the patient's quality of life.

Adolescent↗
PubMed2005

Treatment of ulcerative colitis with a humanized antibody to the alpha4beta7 integrin.

BACKGROUND: Selective blockade of interactions between leukocytes and vascular endothelium in the gut is a promising strategy for the treatment of inflammatory bowel diseases. METHODS: We conducted a multicenter, double-blind, placebo-controlled trial of MLN02, a humanized antibody to the alpha4beta7 integrin, in patients with active ulcerative colitis. We randomly assigned 181 patients to receive 0.5 mg of MLN02 per kilogram of body weight, 2.0 mg per kilogram, or an identical-appearing placebo intravenously on day 1 and day 29. Eligible patients also received concomitant mesalamine or no other treatment for colitis. Ulcerative colitis clinical scores and sigmoidoscopic assessments were evaluated six weeks after randomization. RESULTS: Clinical remission rates at week 6 were 33 percent, 32 percent, and 14 percent for the group receiving 0.5 mg of MLN02 per kilogram, the group receiving 2.0 mg per kilogram, and the placebo group, respectively (P=0.03). The corresponding proportions of patients who improved by at least 3 points on the ulcerative colitis clinical score were 66 percent, 53 percent, and 33 percent (P=0.002). Twenty-eight percent of patients receiving 0.5 mg per kilogram and 12 percent of those receiving 2.0 mg per kilogram had endoscopically evident remission, as compared with 8 percent of those receiving placebo (P=0.007). For the minority of patients in whom an MLN02 antibody titer greater than 1:125 developed, incomplete saturation of the alpha4beta7 receptor on circulating lymphocytes was observed and no benefit of treatment was identifiable. CONCLUSIONS: In this short-term study, MLN02 was more effective than placebo for the induction of clinical and endoscopic remission in patients with active ulcerative colitis.

Adult↗
PubMedDate not supplied

Rapidly progressive bronchiectasis complicating ulcerative colitis in a child.

Patients with ulcerative colitis may have a presentation dominated by extraintestinal manifestations. These manifestations, particularly bronchiectasis, are very rarely seen in pediatric patients. A 13-year-old boy with ulcerative colitis who was diagnosed by colonic mucosa biopsy is presented. He developed unexplained productive cough after the appearance of colonic disease. He was treated and followed up at his primary care hospital with the sole diagnosis of ulcerative colitis, with little attention given to the chest symptoms. The relation of the bronchial involvement to the ulcerative colitis was not established until two years after the onset of disease. Thoracal computed tomography (CT) examination after this period showed evidence of bronchiectasis and pulmonary involvement. Despite prophylactic inhaled corticosteroid treatment, no clinical or radiographic improvement was observed and widespread bronchial destruction developed very rapidly. More effective treatment with oral steroids was probably necessary in this patient, if the early chest symptoms were related to the ulcerative colitis.

Adolescent↗
PubMed2002

Review article: medical treatment of severe ulcerative colitis.

Approximately 15% of patients with ulcerative colitis have a severe attack requiring hospitalization at some time during their illness. This treatment leads to a remission in 60-80% of patients and non-responders may require a total colectomy. Mortality in severe episodes of ulcerative colitis decreased from 31-61% in the 1950s to 5-9% in the 1960s thanks to the introduction of steroids and to a policy of early colectomy. Recently, some new drugs have been shown to be effective in the treatment of severe steroid-refractory ulcerative colitis. This review concentrates on the clinical evaluation, prognostic factors and new developments in medical therapy in severe ulcerative colitis. A retrospective evaluation of a consecutive series of patients with severe ulcerative colitis admitted to a Gastroenterology Department in Torino, Italy, is also reported.

Anti-Bacterial Agents↗
PubMed2003

Progression of flat low-grade dysplasia to advanced neoplasia in patients with ulcerative colitis.

BACKGROUND & AIMS: Long-standing ulcerative colitis has long been recognized as a risk factor for colorectal cancer, but there is still no universal consensus on the optimal management of ulcerative colitis patients with low-grade dysplasia in flat mucosa. Some authorities favor prompt colectomy, whereas others recommend continued surveillance. The purpose of our study was to determine the frequency with which flat low-grade dysplasia in ulcerative colitis progresses to advanced neoplasia (high-grade dysplasia or colorectal cancer) and whether specific variables could predict such progression. METHODS: We reviewed the medical histories, colonoscopic findings, and surgical and pathology reports of 46 patients with ulcerative colitis diagnosed with flat low-grade dysplasia on a surveillance colonoscopy. The rates of neoplastic progression, as well as the frequency of advanced neoplasia, were tabulated. We correlated progression with several clinical and colonoscopic variables: the number of biopsy samples positive for flat low-grade dysplasia, the duration and anatomic extent of disease, patient age, and medication use. RESULTS: Among these 46 patients, there were 7 cases of colorectal cancer, 5 of which were stage II or higher. Unexpected advanced neoplasia occurred in 4 of 17 (23.5%) patients who underwent colectomy for flat low-grade dysplasia. On an actuarial basis, the rate of neoplastic progression was 53% at 5 years. No clinical features predicted progression to advanced neoplasia. Cancers, including 2 at advanced stages, developed despite frequent follow-up surveillance examinations. CONCLUSIONS: A finding of flat low-grade dysplasia during ulcerative colitis surveillance is a strong predictor of progression to advanced neoplasia. Early colectomy should be recommended for such patients.

Actuarial Analysis↗
PubMed1984

Energy level in large intestinal mucosa in patients with ulcerative colitis.

In 7 patients with ulcerative colitis, the energy level in the large intestinal mucosa was investigated. ATP and energy charge in the intestinal mucosa in ulcerative colitis showed lower levels than those of control subjects. Therefore, energy-deficit may exist in the large intestinal mucosa in ulcerative colitis.

Adenine Nucleotides↗