Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0010346 (Crohn's disease)
 21,615 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A retrospective, epidemiological community study of Crohn's disease was performed in Leicestershire from 1972 to 1989. The county population of 930,000 includes 93,000 South Asians. Potential cases were identified from hospital departments of pathology, endoscopy and medical records, in addition to general practitioners. There were 582 cases in Europeans and 28 in South Asians. The incidence of Crohn's disease in Europeans and South Asians has increased, particularly in Muslims. The standardized incidence in South Asians during the 1980s was 2.4/10(5)/year in Hindus, 3.4/10(5)/year in Sikhs and 5.4/10(5)/year in Muslims. The standardized incidence in Europeans has risen significantly to 4.7/10(5)/year from 3.4/10(5)/year in the 1970s (chi 2 = 8.1, p less than 0.005). In Leicester this increase can be accounted for entirely by new cases of colonic disease. All ethnic groups had a similar disease distribution. Small bowel disease was inversely associated with age, whilst colonic disease increased with age. However, the difference in age-specific incidence of Crohn's disease for different age bands at various sites was not significant. Overall, Hindus have a much lower incidence of Crohn's disease than Europeans.
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PMID:Epidemiology of Crohn's disease in Indian migrants and the indigenous population in Leicestershire. 162 Aug 13

The effects of smoking on the localisation and clinical course of Crohn's disease is evaluated in 231 patients. Heavy smokers (greater than 10 cigarettes/day) had an increased risk of operation at least once--odds ratios for heavy smokers compared with never smokers after five and 10 years were 1.14 and 1.24 respectively (p = 0.03 and p = 0.017). The risk of further operations was even higher and after 10 years the odds ratio was 1.79 (p = 0.015). The accumulated number of fistulae and/or abscesses was higher for smokers than for never smokers (p = 0.046). Patients with a high life time tobacco exposure (greater than 150 cigarette years) and heavy smokers (greater than 10 cigarettes/day) had small bowel disease more often than patients with lower life time exposure (less than or equal to 150 cigarette years) and patients smoking less than or equal to 10 cigarettes/day (p = 0.002 and p = 0.045 respectively). The course of Crohn's disease analysed in different ways was unfavourable for smokers, especially heavy smokers. Patients with Crohn's disease should be dissuaded from smoking.
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PMID:Smoking in Crohn's disease: effect on localisation and clinical course. 162 59

The presence or absence of nine autoantibodies were assessed in 44 patients with ulcerative colitis (17 with hyposplenism) and 22 patients with Crohn's disease (eight with hyposplenism). The purpose of the study was to determine whether hyposplenism in inflammatory bowel disease is associated with an increased tendency to autoimmunity, or whether autoimmunity is linked not to hyposplenism itself but to the underlying bowel disease. The results strongly suggest that the latter hypothesis is correct. There was a much higher frequency of autoantibodies in patients with ulcerative colitis than in those with Crohn's disease (P < or = 0.01), suggesting that autoimmune factors are more important in the pathogenesis of ulcerative colitis than in Crohn's disease.
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PMID:Autoimmunity, inflammatory bowel disease and hyposplenism. 167 65

Although the aetiology of inflammatory bowel disease remains elusive, many agents are available for the control of symptoms and inflammation. Knowledge of drug pharmacology, indications and side effects is essential to ensure the best possible clinical care while minimising toxicity and inappropriate use. Sulfasalazine consists of sulfapyridine linked to mesalazine (5-aminosalicylic acid) via an azobond. Its use is indicated in the treatment of mild to moderately active ulcerative colitis and in the prevention of relapse in patients with quiescent disease. Patients with mild to moderate colonic or ileocolonic Crohn's disease also benefit from this drug, as do a proportion of patients with isolated small bowel disease. Sulfasalazine has not been uniformly effective in preventing relapse in Crohn's disease, although many clinicians continue its use in patients who respond initially. A high incidence of side effects which limit therapy include intolerance, hypersensitivity reactions and impairment of male infertility. The newer aminosalicylates offer targeted delivery of mesalazine to the bowel, with fewer side effects. Topical mesalazine has proved extremely effective in patients with distal ulcerative colitis; oral forms are effective in the treatment of mild to moderately active ulcerative colitis and in relapse. Both types appear to be effective in the treatment of Crohn's disease, and possibly in preventing relapse. There is no current clinical advantage of one mesalazine preparation over another, nor is there an indication for their use in sulfasalazine-treated patients who have satisfactory response without adverse effects. Corticosteroids are indicated for more severe disease activity where the aminosalicylates have limited efficacy-specifically to induce remission in patients with severe or refractory ulcerative colitis or Crohn's disease. They should not be used to maintain disease remission or in the prevention of postoperative recurrence. Topical corticosteroids allow their local use in distal colitis with minimal systemic side effects. Long term use is limited by side effects, many of which are dose related, although alternate-day therapy may lessen the incidence. Immunosuppressive agents are beneficial for the treatment of refractory inflammatory bowel disease unresponsive to other medications, and may also facilitate the withdrawal of steroids in refractory patients. Mercaptopurine has an added benefit in the treatment of Crohn's disease fistulae; the role of cyclosporin in bowel disease has not been established and its use cannot currently be recommended. The potential toxicity of immunosuppressive agents warrants careful consideration of their use by both physician and patient. Metronidazole is indicated for the treatment of mild to moderate Crohn's disease, including perineal disease. Common side effects include peripheral neuropathy and nausea.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Risk-benefit assessment of drugs used in the treatment of inflammatory bowel disease. 167 90

Interleukin-2 activity of intestinal lamina propria mononuclear cells is decreased in Crohn's disease and ulcerative colitis patients compared with control patients with noninflammatory bowel disease. Factors that might be responsible for this phenomenon were investigated. Most interleukin-2 activity was produced by helper (CD4+) T cells. These were present in comparable numbers in both inflammatory bowel disease and control cultures, but the frequency of interleukin-2-producing cells was significantly (3-4 times) lower among Crohn's disease and ulcerative colitis than control cells. In agreement with this finding, levels of interleukin-2 messenger RNA were substantially decreased in both forms of inflammatory bowel disease compared with controls. Mucosal CD8+ T cells and plastic-adherent cells were unable to suppress interleukin-2 activity by autologous or allogeneic CD4+ T cells. The rate of interleukin-2 absorption was similar for inflammatory bowel disease and control cells. Induction of interleukin-2 by different stimuli (phorbol ester, phytohemagglutinin, or anti-CD3 monoclonal antibody) before or after incubation under basal conditions ("resting") failed to normalize the capacity to generate interleukin-2 by Crohn's disease and ulcerative colitis cells. Prostanoids (prostaglandin E2 and 6-keto-prostaglandin F1 alpha) were produced in large amounts in cultures of inflammatory bowel disease cells, but inhibition by indomethacin failed to restore interleukin-2 activity to control levels. Finally, supernatants from Crohn's disease and ulcerative colitis cell cultures failed to suppress interleukin-2 production by control CD4+ T cells. Our results show that the low interleukin-2 activity detected in inflammatory bowel disease mucosa is not caused by activated suppressor cells, excessive lymphokine utilization or immune stimulation, a defective response to activation signals, or production of inhibitory substances. Rather, the low interleukin-2 activity appears to be related to a loss of interleukin-2-producing mucosal CD4+ T cells. It is concluded that abnormalities of intestinal CD4+ T-cell function are associated with the immunopathogenesis of Crohn's disease and ulcerative colitis.
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PMID:Loss of interleukin-2-producing intestinal CD4+ T cells in inflammatory bowel disease. 168 26

Nine patients with lymphoma occurring in association with inflammatory bowel disease were admitted to The Mount Sinai Hospital between 1960 and 1983. Five (two men and three women) occurred among 1156 patients (0.43%) with ulcerative colitis (UC) and four (men), among 1480 patients (0.27%) with Crohn's disease (CD), a strong male preponderance in the latter group. In all four of the patients with CD and in four of the five patients with UC, the lymphomas were extraintestinal. The mean age of onset of UC in these patients was late (46 years, 19 years older than in our overall series), with lymphomas occurring a mean of only 12 years later. By contrast, patients with CD had bowel disease much younger (mean age, 26 years), and their lymphomas appeared after a longer disease duration (mean, 24 years). The risk factors for the one patient with colonic lymphoma were similar to those with colitis-associated colorectal carcinoma: extensive and long-standing colitis and relatively young age when malignant disease developed. Four of the patients with lymphoma had associated colonic carcinoma; in three of them, the carcinoma appeared within the first decade of colitis, an unusual occurrence. A second malignant lesion also occurred in three patients with UC.
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PMID:Lymphoma in inflammatory bowel disease. 173 11

Oral contraceptive steroids (OCS) are well absorbed from the gastrointestinal tract in humans. However, while the progestogens are almost completely bioavailable, ethinylestradiol (EE2) is subject to extensive first pass metabolism consisting chiefly of conjugation with sulfate in the gut wall. Both EE2 and progestogens are well absorbed in patients with an ileostomy or with diseases such as cystic fibrosis or Crohn's disease. However in patients with celiac disease (gluten-sensitive enteropathy) the gut wall is less able to conjugate EE2 and thus its bioavailability is increased. The bioavailability returns to control values as the disease is improved following gluten withdrawal. Other drugs that are conjugated with sulfate, such as vitamin C and paracetamol, compete for available sulfate when coadministered with OCS leading to high plasma levels of EE2. Enzyme-inducing agents such as rifampicin, phenobarbitone, phenytoin and carbamazepine reduce blood levels of the OCS leading to contraceptive failure. In the case of anticonvulsants (but not rifampicin) this can be easily overcome by increasing the dose of OCS used. Broad-spectrum antibiotics are reported to cause failure of contraception by interfering with the enterohepatic circulation of EE2 but limited systematic studies show no evidence of such an interaction. Nevertheless practitioners are advised to recommend the use of alternative contraceptive precautions for women receiving broad-spectrum antibiotics concurrently with their OCS preparation.
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PMID:Oral contraceptive steroids--pharmacological issues of interest to the prescribing physician. 177 56

Striking differences were observed between the visceral and cutaneous responses after tests with validated Kveim and normal spleen suspensions in a guinea pig model of granulomatous bowel disease. Five of six animals sensitised with BCG showed positive responses at the ileal Kveim test site whereas all six had negative cutaneous Kveim tests. Conversely, two of six animals sensitised with irradiated Mycobacterium leprae showed positive cutaneous Kveim tests and only one a positive response in the ascending colon. All six showed negative responses at the ileal Kveim test site. No positive visceral or cutaneous responses were observed in either group of animals after tests with normal spleen suspension. These findings are discussed in relation to the positive Kveim responses previously reported among patients with Crohn's disease, tuberculoid and lepromatous leprosy, and among seemingly healthy BCG vaccinated subjects. The findings provide further evidence in support of a possible mycobacterial aetiology for sarcoidosis and Crohn's disease.
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PMID:Observations on the Kveim reaction using an animal model of granulomatous bowel disease. 186 34

An epidemiologic study of the incidence of Crohn's disease during the 25-year period 1963-1987 within a geographically well defined area has been performed. The mean annual incidence during the 25 years was 6.1/10(5) inhabitants. During the first quinquennium the incidence was 4.3/10(5) inhabitants, but during the next four quinquennia the incidence was very stable around 6.6/10(5) inhabitants. The point prevalence on 31 December 1987 was 146/10(5), with a male to female ratio of 1:1.15. An analysis of birth cohorts could not reveal any cohort more prone to develop the disease. Of the 246 incidence cases 5 patients had died of Crohn's disease. The percentage of small-bowel disease only was very stable during the whole study period. The proportion of large-bowel disease decreased only slightly, and combined small- and large-bowel disease increased somewhat towards the end of the study period, probably because of better diagnostic methods.
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PMID:The incidence of Crohn's disease is not decreasing in Sweden. 187 42

Many investigators have tried to prove a relationship between Crohn's disease and Mycobacteria. Recent evidence suggests that some autoimmune diseases may be initiated through "molecular mimicry" between mycobacterial stress protein antigens and their human homologs. We investigated whether antibody to stress proteins was more frequent in patients with Crohn's disease than controls. We used ATP binding to separate stress proteins (heat-shock-induced, de novo-synthesized, and constitutively expressed ATP-binding proteins) from crude extracts obtained from Mycobacteria and from an SV40-transformed human epithelial cell line that expresses a heat-shock protein, hsp73, as a complex with SV40 T antigen. We used immunoblots to compare sera from 34 patients with Crohn's disease, 14 with ulcerative colitis, and 14 with duodenal or gastric ulcers (noninflammatory bowel disease control patients). We found no statistically significant pattern or frequency of antibodies against single proteins or a combination of mycobacterial or human stress proteins. These observations do not support the hypothesis that a humoral immune response to stress proteins of Mycobacteria is important in the pathogenesis of Crohn's disease.
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PMID:Investigations on etiology of Crohn's disease. Humoral immune response to stress (heat shock) proteins. 190 Oct 35


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