Showing papers on "Ulcerative colitis published in 1994"

Cyclosporine in Severe Ulcerative Colitis Refractory to Steroid Therapy

Abstract: Background There has been no new effective drug therapy for patients with severe ulcerative colitis since corticosteroids were introduced almost 40 years ago. In an uncontrolled study, 80 percent of 32 patients with active ulcerative colitis refractory to corticosteroid therapy had a response to cyclosporine therapy. Methods We conducted a randomized, double-blind, controlled trial in which cyclosporine (4 mg per kilogram of body weight per day) or placebo was administered by continuous intravenous infusion to 20 patients with severe ulcerative colitis whose condition had not improved after at least seven days of intravenous corticosteroid therapy. A response to therapy was defined as an improvement in a numerical symptom score (0 indicated no symptoms, and 21 severe symptoms) leading to discharge from the hospital and treatment with oral medications. Failure to respond to therapy resulted in colectomy, but some patients in the placebo group who had no response and no urgent need for surgery were subseque...

Transdermal nicotine for active ulcerative colitis.

Abstract: 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...

Ulcerative colitis and Crohn's disease: a comparison of the colorectal cancer risk in extensive colitis.

Abstract: The risk of developing colorectal cancer has been compared in two identically selected cohorts of patients with extensive Crohn's colitis (n = 125) and extensive ulcerative colitis (n = 486). In both groups the effects of selection bias have been reduced wherever possible. There was an 18-fold increase in the risk of developing colorectal cancer in extensive Crohn's colitis and a 19-fold increase in risk in extensive ulcerative colitis when compared with the general population, matched for age, sex, and years at risk. The absolute cumulative frequency of risk for developing colorectal cancer in extensive colitis was 8% at 22 years from onset of symptoms in the Crohn's disease group and 7% at 20 years from onset in the ulcerative colitis group. The relative risk of colorectal cancer was increased in both ulcerative colitis and Crohn's disease among those patients whose colitis started before the age of 25 years. Whether the absolute risk is greater in the younger age group or merely reflects that the expected number of carcinomas increases with age is uncertain. While there is an increased risk of developing colorectal cancer in extensive colitis the number of patients with Crohn's disease who actually develop colorectal cancer is small because many patients with extensive Crohn's colitis undergo colectomy early in the course of their disease to relieve persistent symptoms unresponsive to medical treatment.

Thickness of adherent mucus gel on colonic mucosa in humans and its relevance to colitis.

Abstract: The thickness of adherent mucus gel on the surface of colonic mucosa was measured in surgically resected specimens from 46 'control' patients most of whom had carcinoma of the colon; 12 were from right colon, 17 left colon, and 21 from rectum. In addition specimens were examined from 17 patients with ulcerative colitis and 15 patients with Crohn's disease. In controls a continuous layer of mucus was readily seen on specially prepared sections viewed by phase contrast illumination. Mean values for right and left colon and rectum were 107 (48), 134 (68), and 155 (54) microns respectively with a significant difference between right colon and rectum (p = 0.015). Values in ulcerative colitis showed greater variation and in those areas with acute inflammation mucosa was denuded of the mucus layer. In contrast, values for Crohn's disease were normal or greater than normal in thickness--right colon 190 (83) microns compared with 107 48 microns, p = 0.0093. A series of validation experiments are described for the method used to measure mucus thickness. The possible role of mucus in the pathogenesis of inflammatory bowel disease is discussed.

Similarity of colorectal cancer in Crohn's disease and ulcerative colitis: implications for carcinogenesis and prevention.

Abstract: Colorectal cancer is the most frequent malignant complication in patients with inflammatory bowel disease. Eighty patients with colorectal cancer complicating Crohn's disease (CD) or ulcerative colitis (UC) with median ages at diagnosis of colorectal cancer of 54.5 years and 43.0 years respectively were studied. The median duration of disease to the diagnosis of cancer was long (CD 15 years; UC 18 years). Most cancers developed after more than eight years of disease (CD 75%; UC 90%). Patients with multiple carcinomas at diagnosis were equally common (CD 11%; UC 12%). Carcinoma occurred in the area of macroscopic disease in most patients (CD 85%; UC 100%). Mucinous and signet ring histological features were equally common (CD 29%; UC 21%). Dysplasia was present with similar frequency in both diseases (CD 73%; UC 79%). The overall five year survival rates were also similar (CD 46%; UC 50%). These findings show that carcinomas complicating CD and UC have strikingly similar clinicopathological features and suggest that a common underlying process, such as chronic inflammation, maybe important in the pathogenesis of colorectal carcinoma.

Expression of interleukin-8 gene in inflammatory bowel disease is related to the histological grade of active inflammation.

Abstract: Interleukin-8 (IL-8) is a potent cytokine for recruitment and activation of neutrophils. To visualize its distribution in the intestinal mucosa and to understand better its possible role in the induction and promotion of inflammatory bowel disease, expression of the IL-8 gene was analyzed in resected bowel segments of 14 patients with active Crohn's disease or ulcerative colitis. In situ hybridization with IL-8 anti-sense RNA probes revealed strong and specific signals in the histologically affected mucosa. The number of cells expressing IL-8 gene correlated with the histological grade of active inflammation. In accordance with the characteristic histological signs of active disease, IL-8-expressing cells were diffusely distributed over the entire affected mucosa in patients with ulcerative colitis, whereas in patients with Crohn's disease, IL-8-expressing cells showed a focal distribution pattern. Cells expressing IL-8 were mainly located at the base of ulcers, in inflammatory exudates on mucosal surfaces, in crypt abscesses, and at the border of fistulae. Analysis of semi-serial sections pointed to macrophages, neutrophils, and epithelial cells as possible sources of this cytokine in active inflammatory bowel disease. We consistently failed to detect IL-8 messenger RNA in the mucosa of uninvolved bowel segments and in normal-appearing control mucosa of patients with colon cancer. In contrast, tissue specimens from two patients with acute appendicitis displayed IL-8-expressing cells in the mucosa. These results support the notion that IL-8 plays and important but nonspecific role in the pathogenesis of inflammatory bowel disease and that the production of IL-8 messenger RNA is restricted to areas with histological signs of inflammatory activity and mucosal destruction.

Increased macrophage subset in inflammatory bowel disease: apparent recruitment from peripheral blood monocytes.

Abstract: Mucosal specimens from active Crohn's disease (ileum, n = 6; colon, n = 6), active ulcerative colitis (n = 9), normal ileum (n = 6), and normal colon (n = 6) were subjected to paired immunofluorescence staining for characterisation of macrophage subsets in situ. In the normal state, only few CD68+ macrophages (< 10%) expressing the myelomonocytic L1 antigen (calprotectin) were seen. In inflamed mucosa, especially near small vessels, the CD68+L1+ fraction increased with the degree of inflammation, near ulcers to median 65% (range 35-91%). Cells reactive with the monoclonal antibody RFD7 were also increased in inflammation but less than 5% of them costained for L1 antigen. It is concluded that L1 producing macrophages are distinct from the RFD7+ subset and probably recently recruited from peripheral blood monocytes. Like granulocytes, L1+ macrophages may be important in non-specific defence, providing calprotectin with putative anti-microbial and anti-proliferative properties.

Incidence of inflammatory bowel disease in northern France (1988-1990).

Abstract: There were no data concerning the incidence of inflammatory bowel disease (IBD) in France. The aim of this study was to investigate the incidence of Crohn9s disease and ulcerative colitis in northern France. This prospective population based study was realised through the gastroenterologists of the region Nord-Pas de Calais and the Somme Department. Each gastroenterologist referred patients consulting for the first time with clinical symptoms compatible with IBD. Data were collected by an interviewer practitioner present at the gastroenterologist9s consulting room. Two independent expert gastroenterologists assessed each case in a blind manner and made a final diagnosis of Crohn9s disease, ulcerative colitis, ulcerative proctitis, or unclassifiable chronic colitis. From 1988 to 1990, 1291 cases of IBD were recorded: 674 (52%) Crohn9s disease, 466 (36%) ulcerative colitis including 162 proctitis (35%), and 151 (12%) unclassifiable chronic colitis. The mean annual incidence was 4.9 per 100,000 for Crohn9s disease and 3.2 for ulcerative colitis. The sex ratio F/M was 1.3 for Crohn9s disease and 0.8 for ulcerative colitis. The highest age specific incidence rate for Crohn9s disease was between 20 and 29 years: 13.1 for women and 9.8 for men. The highest age specific incidence rate for ulcerative colitis was between 20 and 39 years: 5.5 for women and 6.5 for men. This first French prospective study has shown an incidence rate for Crohn9s disease comparable with that seen in north European studies but lower than that seen for ulcerative colitis. These results could be related to the different environmental factors or the genetic background of the population studied, or both.

Colonoscopy of acute colitis. A safe and reliable tool for assessment of severity.

Abstract: Complications that might lead to surgery in severe attacks of ulcerative colitis have been found to be correlated with the depth of colonic ulcerations as measured by pathological examination of colectomy specimens. In order to evaluate the value of colonoscopy for the assessment of colonic ulcerations, we have reviewed the clinical, biological, colonoscopic, and anatomical findings in 85 consecutive patients with attacks of ulcerative colitis involving at least the rectosigmoid and part of the descending colon, seen in our center between 1981 and 1989. All had colonoscopy performed by a senior endoscopist at entry. Extensive deep colonic ulcerations were diagnosed in 46 of them, and moderate endoscopic colitis in 39. No complication related to colonoscopy occurred except for one colonic dilatation. Forty-three of the 46 patients with severe endoscopic colitis were operated upon; 38 of them failed to improve with high-dose corticosteroids and five had a toxic megacolon. Extensive ulcerations reaching at least the circular muscle layer were found at pathological examination of colectomy specimen in 42 of the 43 patients. Conversely, 30 of 39 patients with moderate endoscopic colitis went into clinical remission with medical treatment, and only nine patients needed further surgery because of medical treatment failure. Six of these nine patients underwent another colonoscopy prior to colectomy, and all six showed features of severe endoscopic colitis. Deep ulcerations reaching the circular muscle layer were found at pathological examination in five of these six patients and in one additional patient whose colonoscopy had been performed 21 days before colectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

High frequency of silent inflammatory bowel disease in spondylarthropathy.

Abstract: Objective. To search for an association between gut infection, gut inflammation, and spondylarthropathies. Methods. Ileocolonoscopy was performed in 118 patients with various inflammatory and noninflammatory joint diseases and in 24 patients with uncomplicated acute bacterial gastroenteritis. Results. Endoscopic lesions were more frequent in patients with spondylarthropathy (44%) compared with those with other inflammatory arthritides (6%; P = 0.001). Ileal changes were observed only in patients with spondylarthropathy (20% versus 0%; P = 0.01). Inflammatory bowel disease was the endoscopic diagnosis in 19% of the arthritis patients. Possible or definite Crohn's disease was diagnosed in 26% of patients with chronic spondylarthropathy, and ulcerative colitis in 1 patient with rheumatoid arthritis and in 1 with chronic uroarthritis. Histologic evidence of inflammation differed less distinctly than endoscopy findings between patient groups. There was no association of gut lesions with the use of nonsteroidal antiinflammatory drugs or with the presence of HLA-B27. Conclusion. Gut inflammation is frequent in patients with spondylarthropathy, and one-fourth of the patients who have chronic disease have early features of Crohn's disease.

Ulcerative colitis and Crohn's disease

Abstract: In the past four years three excellent and comprehensive books on inflammatory bowel disease have been published.*RF 1-3* In a total of 1812 pages 156 contributors provide detailed accounts of the recent striking rise in the incidence of Crohn's disease but not ulcerative colitis in most developed countries; patients' genetic disposition (the dis-eases are apparently not HLA related); and clinical features, immunology, pathology, complications, and management options. Can there be much left to find out? Regrettably for the 120 000 or so patients with inflammatory bowel disease in Britain, from toddlers to octogenarians, the answer is yes. And despite inflam-matory bowel disease being unfashionable and attracting little research funding, there is a wealth of research going on. Theories of the cause of inflammatory bowel disease abound. Current front runners include a range of types of immune dysregulation, such as abnormally vigorous stimulation of the gut immune system by products of the commensal flora, inappropriate activation of a single component among the many gut immune cells and mediators, or failure of an inhibitory signal that normally switches off a protective local inflammatory reaction. …

Intestinal permeability in patients with Crohn's disease and ulcerative colitis and their first degree relatives.

Abstract: Increased intestinal permeability in patients with Crohn's disease and their first degree relatives has been proposed as an aetiological factor. The nine hour overnight urinary excretion of polyethyleneglycol-400 (PEG-400) and three inert sugars (lactulose, l-rhamnose, and mannitol) was used to test the permeation in 47 patients with Crohn's disease of whom 18 had at least one first degree relative with inflammatory bowel disease (2BD) and 52 patients with ulcerative colitis of whom 16 had at least one first degree relative with IBD. A total of 17 first degree relatives with IBD and 56 healthy first degree relatives were included. Thirty one healthy subjects not related to patients with IBD served as controls. No significant differences in PEG-400 permeation were found between the groups of patients, relatives, and controls, or between diseased and healthy relatives. The permeability to lactulose, rhamnose, and mannitol similarly did not differ between the three groups. This study challenges the previously reported findings of increased PEG-400 permeation in patients with Crohn's disease and in their healthy and diseased first degree relatives. There was no increase in permeability in a similar group of ulcerative colitis patients and their families.

Observer variation and discriminatory value of biopsy features in inflammatory bowel disease.

Abstract: If skilled histopathologists disagree over the same biopsy specimen, at least one must have an incorrect interpretation. Thus, disagreement is associated with, although not the cause of, diagnostic error. The present study aimed to determine the magnitude of variation among 10 observers with a special interest in gastrointestinal histopathology. They independently interpreted the same biopsy specimens for morphological features which may discriminate between patients with Crohn's disease and ulcerative colitis and normal subjects. Thirty of 41 features had agreement measures significantly better than expected by chance (p < 0.05). The range of agreement in the 45 observer pairs over the final diagnosis was 65-76%. There was good agreement in discriminating between normal slides and those showing confirmed inflammatory bowel disease. For normal slides, however, the term nonspecific inflammation was often applied and without any consistency. In addition, true Crohn's disease slides were often and consistently thought to be ulcerative colitis. Having identified 11 important discriminatory morphological features, two multiple regression analyses were then carried out to produce a scoring system for inflammatory bowel disease. These results suggest there is considerable room for improvement in the reliability of colonic biopsy specimen interpretation and that this could probably be achieved using more exact definitions of morphological features and diseases.

Longitudinal growth in children and adolescents with inflammatory bowel disease.

Abstract: SummaryWeight and height were followed longitudinally from birth to adulthood in children with inflammatory bowel disease living in a defined area of Sweden, 1983 through 1987; 124 children out of a possible 128 were studied. During the year preceding diagnosis, height growth velocity was significantly reduced in both ulcerative colitis and Crohn's disease. At the time of diagnosis, weight-for-height was subnormal in both children with ulcerative colitis (p < 0.05) and those with Crohn's disease (p < 0.001), while height was reduced only in children with Crohn's disease (p < 0.05). Weight for height was normalized within one year in ulcerative colitis, after the initiation of medical therapy. In Crohn's disease, weight-for-height improved during the years following diagnosis but height remained subnormal. Children with ulcerative colitis reached puberty at the normal time and their final heights became normal. In children with Crohn's disease, puberty was delayed (p < 0.001) and final height was reduced (p < 0.01). The impact of inflammatory bowel disease on growth was substantial, but it was smaller in this study than in many other published studies. The possible reasons for this difference include use of population-based material and a relatively short interval between the first symptoms and the start of treatment. Our findings indicate that, although final height was significantly reduced in children with Crohn's disease, delayed puberty reduced the negative effects on permanent adult height, to a certain extent compensating for the period of poor growth earlier in life.

Clinicopathological characteristics of colorectal carcinoma complicating ulcerative colitis.

Abstract: This study examined three features associated with colorectal carcinoma complicating ulcerative colitis: (a) the distribution of 157 cancers in 120 patients with ulcerative colitis treated at St Mark's Hospital between 1947 and 1992; (b) the frequency at which dysplasia was found at a distance from the tumour in 50 total proctocolectomy specimens in which an average of 27 histology blocks were reviewed, and (c) the five year survival rate according to Dukes's stage and participation in a surveillance programme. Of 157 carcinomas, 88 (56%) occurred in the rectosigmoid, 19 (12%) in the descending colon or splenic flexure, and 50 (32%) in the proximal colon. Among the 120 patients, the rectum or sigmoid colon contained cancer in 81 (67.5%). Dysplasia was detected in 41 of 50 reviewed proctocolectomy specimens (82%). Dysplasia distant to a malignancy occurred in 37 (74%); two were classified indefinite, probably positive, 19 were low grade, and 16 were high grade; in 18 specimens there was an elevated dysplastic lesion. Survival was related to the Dukes's stage: about 90% of patients with Dukes's A or B cancer were alive at five years. The five year survival of 16 patients in whom cancer developed during surveillance was 87% compared with 55% of 104 patients who did not participate in surveillance (p = 0.024).