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PubMed1978

IgA-related defective neutrophil chemotaxis in ulcerative colitis.

A case of ulcerative colitis with defective neutrophil chemotaxis, improved after short sulfasalazine therapy, is reported. This is the first case of this disease in which the chemotactic defect was characterized as a serum inhibitor, directed toward autologous and homologous neutrophils and associated with circulating IgA. Preincubation of normal neutrophils with increasing concentrations of patient's serum resulted in a dose-related inhibition, suggesting a stoichiometric relationship between humoral inhibitory power and neutrophils.

Adult↗

PubMed1982

Diagnosis and medical treatment of ulcerative colitis.

Acute attacks of ulcerative colitis should be treated without delay and corticosteroids should be used systemically and topically. For patients with severe attacks, prognostic indicators and criteria for proceeding to urgent colectomy are well defined. In fact, with good medical management the surgeon should only rarely have to operate on a moribund patient, even when an emergency or urgent colectomy is indicated. The mortality rate in patients with severe attacks requiring surgery is low in specialist centres. When patients have gone into remission on corticosteroids, these should be tailed off and the patients maintained indefinitely on sulphasalazine. Currently there is considerable interest in the development of pro-drugs which will contain the 5-aminosalicylic acid moiety but not the sulphapyridine.

Acute Disease↗

PubMed1995

Worsening risk for the development of dysplasia or cancer in patients with chronic ulcerative colitis.

OBJECTIVES: Patients with ulcerative colitis (UC) are at increased risk for developing dysplasia or cancer (neoplasia) and are usually offered colonoscopic surveillance to reduce their risk of cancer-related mortality. The causes of neoplasia may be related to features of UC (the extent, severity, activity, and age at onset of the disease) and to environmental factors (medications, vitamin and mineral supplementation, diet, or industrial pollutants). To determine whether and how the risk (and hence the risk factor profile) for the development of neoplasia changes over time, we conducted an historical cohort study. METHODS: From 445 adult patients with UC proximal to the splenic flexure seen in the Department of Gastroenterology between 1986 and 1992, a random sample of 209 patients was selected. Patients with UC for less than 8 yr or colectomy or neoplasia detected within 2 yr of referral were excluded, leaving 98 patients in the cohort, half of whom had disease onset during or before 1972. RESULTS: After controlling for age at disease onset and duration of disease at first colonoscopy, we found that patients with an earlier year of disease onset were 85% less likely to develop neoplasia than patients with a later year of disease onset (hazard rate ratio 0.15, 95% confidence interval 0.03-0.66). CONCLUSION: These data suggest that the risk for developing neoplasia in UC patients increases with increasing calendar year, implying a worsening risk factor profile.

Adult↗

PubMed2002

Chromosomal instability in ulcerative colitis is related to telomere shortening.

Ulcerative colitis, a chronic inflammatory disease of the colon, is associated with a high risk of colorectal carcinoma that is thought to develop through genomic instability. We considered that the rapid cell turnover and oxidative injury observed in ulcerative colitis might accelerate telomere shortening, thereby increasing the potential of chromosomal ends to fuse, resulting in cycles of chromatin bridge breakage and fusion and chromosomal instability associated with tumor cell progression. Here we have used quantitative fluorescence in situ hybridization to compare chromosomal aberrations and telomere shortening in non-dysplastic mucosa taken from individuals affected by ulcerative colitis, either with (UC progressors) or without (UC non-progressors) dysplasia or cancer. Losses, but not gains, of chromosomal arms and centromeres are highly correlated with telomere shortening. Chromosomal losses are greater and telomeres are shorter in biopsy samples from UC progressors than in those from UC non-progressors or control individuals without ulcerative colitis. A mechanistic link between telomere shortening and chromosomal instability is supported by a higher frequency of anaphase bridges--an intermediate in the breakage and fusion of chromatin bridges--in UC progressors than in UC non-progressors or control individuals. Our study shows that telomere length is correlated with chromosomal instability in a precursor of human cancer.

Adult↗

PubMed1993

Effect of topical 5-aminosalicylic acid (5-ASA) therapy on rectal mucosal biopsy morphology in chronic ulcerative colitis.

Classic teaching emphasizes that chronic ulcerative colitis is characterized morphologically by the presence of fixed architectural and cellular mucosal changes that categorize the process as chronic. To examine the effect of topical 5-aminosalicylic acid (5-ASA) enemas on the presence of six histological features of chronicity in established chronic ulcerative colitis, 123 mucosal biopsies were taken prospectively at 1-month intervals, all from the same anatomic location (10 cm), from 14 patients treated with either 5-ASA or placebo enemas. The biopsies were evaluated for the presence of mixed inflammation in the lamina propria, crypt architectural abnormalities, basally located lymphoid aggregates, basal plasmacytosis, villiform surface epithelial configuration, and Paneth cell metaplasia. Overall, 29% of biopsies from 64% of patients were histologically normal (no chronic features, no active disease). Compared with patients treated with placebo enemas, patients treated with 5-ASA enemas showed a significantly higher percentage of normal biopsies (36% ASA group vs. 12% placebo group; p = 0.005) and a lower percentage occurrence of each individual histological feature of chronicity. In addition, patients treated with 5-ASA had a higher average number of normal biopsies per patient (3.0) than those treated with placebo enemas (1.3). Therefore, histologically normal-appearing mucosal biopsies do occur in established cases of chronic ulcerative colitis, and this finding is enhanced by treatment with 5-ASA enemas. Awareness of these results should prevent the presence of normal rectal mucosal biopsy findings in chronic ulcerative colitis patients from being misinterpreted as either evidence against this diagnosis or as representing focal skip areas characteristic of Crohn's disease.

Administration, Topical↗

PubMed2003

[5-aminosalicylic acid in the treatment of ulcerative colitis and Crohn's disease].

BACKGROUND: Ulcerative colitis and Cohn's disease are characterised by exacerbations and remissions. Their aetiology is not known and treatment modalities are therefore focused on the inflammation. MATERIAL AND METHODS: A review is given of the literature on the clinical efficacy and safety of treatment with 5-aminosalicylates. RESULTS: Aminosalicylic acid has a well-documented efficacy in the acute treatment of mild and moderate ulcerative colitis as well as in maintaining remission in these patients. Its value for patients with Cohn's disease is at the best modest. There are several possible explanations: the variability of disease location, drug disposition and topical availability of the active drug. The usefulness of aminosalicylates has been demonstrated in the long-term treatment of ulcerative colitis for the prevention of colorectal cancer. 5-aminosalicylates have side effects that are comparable with placebo. INTERPRETATION: The benefit of 5-aminosalicylic acid is well documented in the treatment of active ulcerative colitis and for maintaining remission. The opposite is seen in relation to Cohn's disease.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1992

Immunoglobulin G (IgG), IgG1, and IgG2 determinations from endoscopic biopsy specimens in control, Crohn's disease, and ulcerative colitis subjects.

Acute exacerbations of chronic inflammatory bowel disease (ulcerative colitis and Crohn's disease) are characterised by an increase in immunoglobulin G (IgG) positive cells in the mucosa, whereas uninflamed mucosa of inflammatory bowel disease patients displays only moderately increased or normal numbers of these cells. Previous data suggest that acute exacerbations of ulcerative colitis and Crohn's disease can be distinguished by different IgG subclass expression of mucosal immunocytes and a different IgG subclass production pattern of lamina propria lymphocytes. A procedure to obtain enough intestinal mononuclear cells from biopsy specimens to measure in vitro IgG and IgG1 production in control subjects and various patient groups has been established. IgG2 could be measured in Crohn's disease and ulcerative colitis only, as the concentrations in control subjects were below the sensitivity of the ELISA method. We found that IgG and IgG1 production correlated with the degree of local inflammation in both diseases, even in slightly inflamed mucosa, compared with control subjects. The proportion of IgG1 subclass was significantly increased in severely inflamed mucosa of both ulcerative colitis and Crohn's disease patients. A major difference between Crohn's disease and ulcerative colitis mucosa is apparent in mild or no inflammation. In Crohn's disease mucosa in remission, the IgG1/IgG ratio is comparable with that in controls, yet ulcerative colitis mucosa still displays significantly increased proportions of IgG1. In addition, the IgG2/IgG ratio is 0.12 in ulcerative colitis and 0.19 in Crohn's disease patients. The results show the dependence of local IgG and IgG1 production on the degree of inflammation and that an increase in subclass IgG1 in ulcerative colitis is present at all stages, including remission. These findings support the hypothesis that different immunoregulatory mechanisms are involved in Crohn's disease and ulcerative colitis. Environmental stimuli or genetic background may be responsible for the observed differences.

Biopsy↗

PubMed1955

Ulcerative colitis.

In the early stages ulcerative colitis is reversible and a normal bowel can be regained. This is facilitated by the use of cortisone which should be given promptly during the first attack. Surgical operation has an important role in helping to reduce the high initial mortality and in overcoming invalidism in the chronic phase.A clear understanding of the role of emotional tension enables the internist to make an appreciable contribution to the management of the disease.

Colitis, Ulcerative↗

PubMed2002

[Treatment of ulcerative colitis and Crohn's disease with monoclonal antibody].

Ulcerative colitis and Crohn's disease are nonspecific inflammatory diseases of unknown etiology. Recent immunological studies have shown that proinflammatory cytokines and adhesion molecules play an important role in the pathogenesis of ulcerative colitis and Crohn's disease. Therefore, monoclonal antibodies to proinflammatory cytokines and adhesion molecules are used to suppress the mucosal inflammatory response in experimental colitis and ulcerative colitis and Crohn's disease. Anti-TNF alpha antibody and anti-alpha 4 beta 7 integrin antibody are well-tolerated and effective for treatment of patients with Crohn's disease. This review described clinical features and immunopathophysiology of ulcerative colitis and Crohn's disease, proinflammatory cytokines and immunosuppressive cytokines and adhesion molecules involved in the pathogenesis of both disease, and treatment of both diseases with monoclonal antibodies.

Animals↗

PubMedDate not supplied

Does colitis associated with primary sclerosing cholangitis represent an actual subset of ulcerative colitis?

BACKGROUND/AIMS: The clinical course and endoscopic features of colitis associated with primary sclerosing cholangitis have not been well documented. METHODOLOGY: Since 1980, a total of 485 patients with ulcerative colitis have been seen in our departments. During this period, we experienced 6 patients with primary sclerosing cholangitis, 4 of whom had ulcerative colitis concomitantly. RESULTS: Colitis preceded primary sclerosing cholangitis in 3 of the 4 patients. There were 2 males and 2 females. One patient had left-sided colitis while 3 had total colitis, 1 with a first attack and 3 with relapsing-remitting type. Two of the 4 patients had colonoscopically dominant inflammation in the proximal colon with continuous histological inflammation from the rectum to the proximal colon. Three colitic patients have been well controlled with oral sulfasalzine or mesalazine administration. Only 1 female patient had been hospitalized twice for moderately severe attacks of ulcerative colitis that required systemic prednisolone administration, however, this patient quickly responded to this treatment for each admission. CONCLUSIONS: Colitis associated with primary sclerosing cholangitis exhibited atypical colonoscopic findings and exhibited milder disease activity than ulcerative colitis without primary sclerosing cholangitis.

Adult↗

PubMed2004

Adenomatous colonic polyps are rare in ulcerative colitis.

BACKGROUND: Uncertainty exists as to whether dysplastic polyps in ulcerative colitis should always be managed as dysplasia-associated lesions/masses requiring colectomy, or whether some can be managed by polypectomy. The prevalence of non-inflammatory polyps in ulcerative colitis is unknown. AIM: To compare dysplastic polyp occurrence in patients with ulcerative colitis and in patients without inflammatory bowel disease. METHODS: The clinical, endoscopic and histological records of 150 ulcerative colitis patients (median disease duration, 10 years; 57% with pancolitis) undergoing colonoscopy were scrutinized for any polyp history. Two hundred and five patients undergoing colonoscopy for altered bowel habit, but without features suggestive of polyp presence, were used as a control group. Immunohistochemical staining of flat and polypoid mucosa for p16, beta-catenin, p53 and cyclo-oxygenase-2 was compared in the two groups. RESULTS: Only six (4%) ulcerative colitis patients had ever had dysplastic polyps. Two had single adenomatous polyps proximal to the colitis segment. Of the four patients with dysplastic polyps within colitic mucosa, two were treated endoscopically, but in two the lesions were considered to be dysplasia-associated lesions/masses and colectomy was advised. In contrast, 24 controls had at least one adenomatous polyp (chi(2) = 6.7, P < 0.01). Ten (6.7%) ulcerative colitis patients and 24 (12%) control patients had metaplastic polyps (N.S.). Immunohistochemical staining was not discriminatory. CONCLUSION: Despite the increased cancer risk in long-standing ulcerative colitis, adenomatous polyps arise less frequently in ulcerative colitis patients than in patients without ulcerative colitis.

Adenomatous Polyposis Coli↗

PubMed2005

Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial.

BACKGROUND & AIMS: Ulcerative colitis is most common in Western industrialized countries. Inflammatory bowel disease is uncommon in developing countries where helminths are frequent. People with helminths have an altered immunological response to antigens. In animal models, helminths prevent or improve colitis by the induction of regulatory T cells and modulatory cytokines. This study determined the efficacy and safety of the helminth Trichuris suis in therapy of ulcerative colitis. METHODS: This was a randomized, double blind, placebo-controlled trial conducted at the University of Iowa and select private practices. Trichuris suis ova were obtained from the US Department of Agriculture. The trial included 54 patients with active colitis, defined by an Ulcerative Colitis Disease Activity Index of > or =4. Patients were recruited from physician participants and were randomly assigned to receive placebo or ova treatment. Patients received 2500 Trichuris suis ova or placebo orally at 2-week intervals for 12 weeks. RESULTS: The primary efficacy variable was improvement of the Disease Activity Index to > or =4. After 12 weeks of therapy, improvement according to the intent-to-treat principle occurred in 13 of 30 patients (43.3%) with ova treatment compared with 4 of 24 patients (16.7%) given placebo (P = .04). Improvement was also found with the Simple Index that was significant by week 6. The difference in the proportion of patients who achieved an Ulcerative Colitis Disease Activity Index of 0-1 was not significant. Treatment induced no side effects. CONCLUSIONS: Ova therapy seems safe and effective in patients with active colitis.

Administration, Oral↗

PubMed1981

Extended management of chronic ulcerative colitis and the problem of carcinoma.

Patients with ulcerative colitis provide a significant challenge to the primary care physician for a variety of reasons. Ulcerative colitis can be a severe or even fulminating disease or can be chronic, indolent, and therapeutically unresponsive. Patients afflicted with ulcerative colitis are often young, mobile, may have a suboptimal compliance with various forms of therapy, and may be lost to followup. Assessment of the individual therapeutic response as well as its relationship to the overall prognosis for a given patient may be difficult. Steroid side effects may also complicate the picture, leaving the patient the difficult alternative of total proctocolectomy with permanent ileostomy. Added to these factors is the recognition that under 50 per cent of patients with ulcerative colitis will undergo surgery and the remainder will be at increased risk for the subsequent development of colonic carcinoma. Although there has been much recent emphasis on adequate and cost-effective surveillance techniques to detect early carcinoma of the colon in ulcerative colitis, clarification of the value of colonoscopy and the definition of dysplasia are relatively recent developments. That the medical literature is often confusing only adds to the complexity and clinical challenge. Finally, although the cancer problem has been dominant, the challenge to the clinician is to try to assist the patient afflicted with ulcerative colitis to attain a meaningful and productive role in society.

Chronic Disease↗

PubMed1998

[Ulcerative colitis and pregnancy].

BACKGROUND: The evolution of ulcerative colitis in pregnancy is far from clear. While some authors state that the disease aggravates during this period, others do not share this opinion. AIM: To assess the evolution of ulcerative colitis in pregnancy. PATIENTS AND METHODS: A paired case-control design was used in which 15 women, with diagnosed ulcerative colitis at the moment of becoming pregnant, were followed for 12 months and the activity of the disease was compared with that of the 12 months preceding the pregnancy. The activity of the disease in the period preceding the pregnancy was gathered retrospectively from the patient's charts. RESULTS: The mean age of the first ulcerative colitis crisis was 24 years. It was moderate in 49% and severe in 35% of women. During pregnancy 55% of women did not have a crisis, compared with 26.7% during the period preceding pregnancy (relative risk of not having a crisis during pregnancy of 1.7). During both periods, seven women had digestive complications, whereas extra digestive complications were not observed in 60% of patients during pregnancy and 11.8% of patients during the preceding period. Perinatal results were similar to those of the general population. CONCLUSIONS: In our group of patients the evolution of ulcerative colitis was better during pregnancy, reflected by a lower number of crisis.

Colitis, Ulcerative↗

PubMed1997

Nicotine: does it have a role in the treatment of ulcerative colitis?

OBJECTIVES: To review the epidemiology, pathophysiology, diagnosis, clinical manifestations, and treatment of ulcerative colitis, with emphasis on the relationship between smoking, nicotine, and ulcerative colitis, and the most recent clinical trials on the use of nicotine in the treatment of ulcerative colitis. DATA SOURCES: A MEDLINE search (1966 to present) of English language literature regarding the use of various nicotine dosage forms in the treatment of ulcerative colitis. Additional literature was obtained from bibliographic literature searches of appropriate articles identified through this search. DATA SELECTION: All appropriate journal articles focusing on ulcerative colitis and current treatment options, with emphasis on clinical trials involving the use of nicotine, were considered by the authors for inclusion. DATA SYNTHESIS: Ulcerative colitis is a chronic inflammatory disease state of unknown etiology. Its progression is erratic, with patients experiencing periods of exacerbations and remissions. Current therapeutic options have yielded less than satisfactory results. With the discovery of the potential relationship between nonsmoking status and the onset of ulcerative colitis and the development of various nicotine dosage forms came the hypothesis that nicotine may play a protective role against the development of ulcerative colitis and maintenance of remission. Hence, investigators began conducting clinical trials on the use of available nicotine dosage forms in the management of ulcerative colitis. The most recent clinical trials on the use of nicotine in the management of ulcerative colitis have suggested that nicotine, in combination with conventional pharmacologic therapy, may result in clinical improvement in some patients. The use of nicotine as a single agent cannot be recommended at this time. Clinical trials have also revealed poor patient tolerability and long-term compliance due to nicotine's significant adverse effect profile. Overall, investigation of nicotine in the treatment of ulcerative colitis has yielded disappointing results. CONCLUSION: Nicotine cannot be recommended as adjunctive or single therapy for the treatment of ulcerative colitis and will not alter current treatment options. Further research in this area is necessary with focus on enhancing understanding of disease pathophysiology, therapeutic effects of nicotine, and reducing nicotine's adverse effect profile.

Clinical Trials as Topic↗

PubMed1999

Biased JH usage in plasma cell immunoglobulin gene sequences from colonic mucosa in ulcerative colitis but not in Crohn's disease.

BACKGROUND: Ulcerative colitis is an inflammatory disease of the colonic and rectal mucosa. Autoantibodies have been observed in ulcerative colitis which may have a role in the pathogenesis of the disease. Evidence also suggests that there is an hereditary predisposition towards the disease, although no individual genes have been identified. AIMS: This is a pilot study of immunoglobulin heavy chain genes (IgH) in ulcerative colitis to determine whether they have any particular genetic characteristics which may lead to a better understanding of the disease aetiology. SUBJECTS: Colonic or rectal tissue was obtained from five children with ulcerative colitis. Tissue was also obtained from five children with Crohn's disease and five children who did not have inflammatory bowel disease as controls. METHODS: B cells and IgD+ B cells were identified by immunohistochemistry on frozen sections. Areas of lamina propria containing plasma cells, and areas of IgD+ B cells were microdissected. The immunoglobulin genes were PCR amplified, cloned, and sequenced. Sequences were analysed for content of somatic mutations and composition of heavy chain. RESULTS: An increase in the use of JH6 and DXP'1, and a decrease in the use of JH4, gene segments in immunoglobulin genes from lamina propria plasma cells, and from virgin IgD+ B cells, was found in patients with ulcerative colitis. These biases were not present in the control groups. CONCLUSIONS: There is a fundamental difference in the immunoglobulin genes from patients with ulcerative colitis. Whether this is caused by a difference in content of immunoglobulin gene segments in the germline or a difference in the recombination mechanism is not known.

Adolescent↗

PubMed1994

[Autoimmune hemolytic anemia, infrequent complication of ulcerative colitis].

Autoimmune hemolytic anemia is a rare complication of ulcerative colitis. A retrospective review of the cases of ulcerative colitis treated at our hospital between January 1984 and August 1993 showed that, among 210 patients, three presented autoimmune hemolytic anemia with a positive direct Coomb's test. They were two men and one woman suffering from a moderately active ulcerative colitis that affected the left colon. The hemolysis was diagnosed before the onset of colitis in two cases and after it in the other. In the only patient treated with sulphasalazine, this drug was stopped without improvement. All the patients were treated with steroids, with resolution of the anemia in one of them. Healing was achieved with splenectomy in the other two. Colectomy was not necessary in any case. After suppression of sulphasalazine and treatment with steroids, the next therapeutic option in patients with ulcerative colitis and autoimmune hemolytic anemia should be splenectomy, whereas colectomy should be only used with unresponsive patients, as well as with those affected by severe ulcerative colitis refractory to steroids. In patients presenting with ulcerative colitis and anemia, the possibility of autoimmune hemolytic anemia has to be considered since--in spite of being rare--it is responsive to proper treatment.

Adult↗

PubMed1995

Exacerbation of chronic ulcerative colitis with mesalamine.

Activation of ulcerative colitis with mesalamine has rarely been reported. In case 1, a 34-year-old man was treated with oral mesalamine, resulting in an exacerbation of colitis that rapidly improved with glucocorticoids and mesalamine withdrawal. Oral cromolyn sodium and occasional low-dose prednisone therapy has maintained long-term remission. In case 2, a 28-year-old man receiving prednisone treatment developed chest pain and myalgias 1 week after initiation of mesalamine that resolved on mesalamine withdrawal. A lower dose of mesalamine with continued glucocorticoids resulted in clinical improvement, and both drugs were tapered. Mesalamine sensitivity was documented endoscopically and histologically by evaluating mucosal changes after two mesalamine enemas during a 24-hour period. There was dramatic progression from quiescent disease to active colitis in 24 hours. Mesalamine sensitivity must be included in the differential diagnosis of ulcerative colitis exacerbations. Concurrent steroid therapy can suppress systemic side effects, making the diagnosis even more elusive.

Adult↗