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)

The clinical presentation and outcome of 32 children with primary sclerosing cholangitis (PSC) are reviewed, the largest North American series. The majority of patients were diagnosed in their second decade (median age: 13 years). Four children presented before the age of 2 years, but none in the neonatal period. Seventeen patients had inflammatory bowel disease (IBD), all with colitis, 14 ulcerative colitis, and 3 Crohn's disease. Eight patients presented with chronic liver disease before clinical onset of IBD. Only 8 of 32 patients were jaundiced at presentation. Fifteen of 32 had a normal serum alkaline phosphatase (ALP) level at presentation. Nine children presented with features similar to those of autoimmune hepatitis. Cholangiography was performed in all cases and classified by a scoring system specifically developed for pediatric patients. Intrahepatic disease predominated; in only three cases a common bile duct stricture was identified requiring stenting. Findings on the initial liver biopsy were classified according to Ludwig's criteria for staging PSC: there were 15 biopsies in stages 1 to 2 and 17 biopsies stages 3 to 4. HLA class I and II antigens were determined in 27 patients. An increased incidence of HLA B8 and DR2(15) but not DRw52a (DRB3*0101) was found. Anti-neutrophil cytoplasmic antibody (ANCA) was positive in 10 of 24 patients tested. Survival analysis indicated that a later age at presentation, splenomegaly, and prolonged prothrombin time (PT) at presentation were significant contributors to the prediction of poor outcome (i.e., death or listing for transplantation). Liver transplantation was successfully performed in seven children. Physicians must maintain a high index of suspicion of PSC in any child or young adult presenting with chronic liver disease, especially in the presence of IBD, even with a normal serum alkaline phosphatase level.
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PMID:Primary sclerosing cholangitis in 32 children: clinical, laboratory, and radiographic features, with survival analysis. 759 Jun 57

The hypothesis that the colonic epithelium is diffusely abnormal in ulcerative colitis was examined by comparing disease related responses in expression of markers of differentiation by colonic crypt cells to culture with and without butyrate. Cells were isolated from patients with normal colon (15), cancer (24), ulcerative colitis (19), or Crohn's disease (16). Alkaline phosphatase activities were measured in cell homogenates and the rate of glycoprotein synthesis assessed at the end of 24 hours of culture and expressed relative to the rate of protein synthesis as the G:P ratio. Alkaline phosphatase activities, but not G:P ratios, differed across the groups before and after 24 hour culture (p < 0.05), activities being lowest in the cancer group and highest in inflammatory bowel disease groups. Butyrate (1 mM) suppressed alkaline phosphatase activities in the cancer group by mean (SEM) of 17 (4) (p = 0.006) compared with no change in the other groups. Butyrate suppressed G:P ratios only in the cancer (6 (3)%, p = 0.03) and ulcerative colitis groups (5 (3)%, p = 0.04) and the changes in both were different (p < 0.05) from those in normal cells (increase of 10 (7)%). Changes in ulcerative colitis were different from those in Crohn's disease (p = 0.029). Responses were independent of the presence or absence of mucosal inflammation. These data confirm the diffuse nature of epithelial abnormalities in colorectal cancer. In ulcerative colitis, a different pattern of abnormality occurs, supporting the notion that the epithelium is also diffusely abnormal independent of mucosal inflammation.
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PMID:Colonic epithelium is diffusely abnormal in ulcerative colitis and colorectal cancer. 761 74

5-Aminosalicylic acid-O-sulfate (5-ASA sulfate), a new agent for the treatment of ulcerative colitis and Crohn's disease of the large intestine, was investigated for its pharmacokinetic and toxicological properties, following local and systemic application. 5-ASA sulfate can be considered as a non-toxic agent after single oral intake in rats (14-day LD50 > 6000 mg/kg b.w.). Oral application of 2500 mg 5-ASA sulfate/kg b.w./d for 28 days to rats resulted in significantly increased body weight gain and food and water consumption. Alanine aminotransferase and alkaline phosphatase values were elevated in high-dosed (2500 mg/kg b.w./d p.o.) males. Relative liver weights were significantly increased in high-dosed males and females and the macroscopical inspection revealed thickened liver margins. The no-effect level following 28 days of oral application to rats was determined as 500 mg 5-ASA sulfate/kg b.w./d. In acute local tolerance studies in rabbits, 5-ASA sulfate is rated as non-irritant to the skin and the eye. After a single oral administration of 1800 mg 5-ASA sulfate to 5 healthy human test subjects, 5-ASA sulfate was almost completely metabolized by all test subjects within 3 days; mean urinary and faecal excretion of unchanged 5-ASA sulfate amounted to only 6.7% of the administered dose. A high faecal excretion of the active metabolite 5-aminosalicylic acid (5-ASA) (21.2% of the administered dose) and a low urinary excretion (1.4% of the administered dose) were observed.
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PMID:Experimental studies on the pharmacokinetics and toxicity of 5-aminosalicylic acid-O-sulfate following local and systemic application. 774 89

Inflammatory bowel disease (Crohn's disease and ulcerative colitis) is associated with decreased bone mineral density and increased risk of osteoporosis. However, the pathogenesis of this bone loss is not yet fully understood. In the present study we measured lumbar bone mineral density (by dual photon absorptiometry), serum levels of parathyroid hormone (PTH) and vitamin D metabolites, and serum markers of bone turnover (alkaline phosphatase and osteocalcin) in 15 patients with Crohn's disease and in 4 patients with ulcerative colitis. The median duration of the disease was 4 years and the median lifetime steroid dose was 10g of prednisone. We compared our results to a control group of 19 normal persons, who were matched for age and sex to the patients. We found that lumbar bone density was reduced by 11% in patients compared with control persons (Z-score -0.6 +/- 0.6 versus -0.1 +/- 0.8; p < 0.05). In patients, the serum levels of PTH, 25-hydroxyvitamin D3, and calcitriol (1,25(OH)2D3) were significantly reduced compared with control persons. Serum alkaline phosphatase activity (AP) was significantly higher in the patients and was inversely related to lumbar bone density. Osteocalcin values were not different between patients and control persons. There was also no difference in serum levels of calcium between the two groups, whereas phosphorus levels were higher in patients. We conclude that malabsorption of calcium was not a primary cause of bone loss in our patients, because we did not find secondary hyperparathyroidism. Accordingly, we did not find a severe vitamin D deficiency, since 25-hydroxyvitamin D3 levels were within the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bone mineral density and calcium regulating hormones in patients with inflammatory bowel disease (Crohn's disease and ulcerative colitis). 800 8

Liver abscess is a rare but serious complication of Crohn's disease. Intra-abdominal abscesses, fistulous disease, and metronidazole or steroid therapy have all been reported to be important predisposing factors in the pathogenesis of the disease, and the mortality has been reported to be high. We report six patients who developed a liver abscess as a complication of Crohn's disease. Three patients presented with a liver abscess as the first manifestation of Crohn's disease and two others had quiescent disease at presentation. The diagnosis was delayed by 1-8 wk after the onset of fever because of the paucity of signs indicating a hepatic infection. None of the patients had intra-abdominal abscesses, active fistulas, or metronidazole therapy before the onset of symptoms. The only predisposing conditions identified were two minor skin infections in patients developing staphylococcal liver abscesses. Nonoperative catheter drainage was successful in four of the six patients. One patient required surgical placement of drains, and the patient with the longest delay before diagnosis required hepatic lobectomy because of extensive necrosis. Shaking chills, fever with leukocytosis, and an elevated alkaline phosphatase are suggestive of a liver abscess and should prompt an ultrasound examination. Catheter drainage with antibiotic therapy is effective if the liver abscess is diagnosed before extensive necrosis has occurred. Minor skin infections may predispose to staphylococcal liver abscess in some cases.
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PMID:Liver abscess in Crohn's disease. 801 70

In children with inflammatory bowel disease, controversy continues about the use of long-term alternate day prednisone therapy (ADP) to suppress disease activity and to encourage appetite and growth. One possible side effect of both disease process and prednisone therapy is risk of development of osteoporosis. To evaluate this risk factor, growth, biochemical indices of mineral and vitamin D status, and bone mass were measured in nine adolescents with Crohn's disease (CD) who were treated with ADP (0.3 mg/kg > 3 months per year) compared with eight adolescents treated with minimal ADP exposure (< 3 months per year). Single photon densitometry was used to measure bone mineral mass at the 1/3 distal radius three times over 2 years. Mean age of the 17 CD boys was 13.9 +/- 2.1 years at baseline. CD patients had lower bone BMC/BW mineral content/bone width (BMC/BW) compared with age- and height-matched normal boys at all times. The difference was less when compared to height-matched normal values as CD patients were shorter than healthy reference boys. Plasma 1,25-dihydroxyvitamin D, alkaline phosphatase, and parathyroid hormone significantly increased with treatment of disease but there were no differences between treatment groups. CD patients treated with ADP had similar heights and weights at baseline and demonstrated similar linear growth over 2 years (9.1 cm/2 years) to CD patients without ADP (10.3 cm/2 years). In both groups, BMC/BW increased significantly from year 1 to year 2, but absolute values for bone mass did not differ between the groups.
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PMID:Longitudinal assessment of growth, mineral metabolism, and bone mass in pediatric Crohn's disease. 814 96

Serum alkaline phosphatase (ALP) and its isoenzymes - liver (L-ALP), fast liver (F-ALP; also called high-molecular-weight ALP), bone (B-ALP) and intestinal (I-ALP) - were measured by agarose electrophoresis after pretreatment of sera with neuraminidase in 100 patients with Crohn's disease (CD) and 100 age-matched healthy controls. Total ALP was increased in 25 patients whereas the isoenzymes F-ALP, L-ALP, B-ALP, I-ALP were increased in 64, 84, 16 and 8%, respectively. But also in patients with CD and with normal ALP the isoenzymes were high in 39, 15, 1 and 1%, respectively. Total ALP, L-ALP and F-ALP correlated with gamma-glutamyltransferase (GGT) (tau = 0.22, 0.20 and 0.26, respectively, p < 0.05), but F-ALP also correlated with parameters of disease activity such as Crohn's disease activity index (CDAI), orosomucoid (OM) and erythrocyte sedimentation rate (tau = 0.28, 0.23 and 0.37, respectively, p < 0.001). In 38 patients, ALP and isoenzymes were controlled within 6 months. In these patients there were correlations between changes of total ALP and F-ALP with changes of inflammatory activity such as CDAI (tau = 0.31, p = 0.07 and tau = 0.30, p = 0.01) or OM (tau = 0.26 and 0.25, p < 0.05). Therefore, ALP seems to be influenced by inflammatory activity mainly via F-ALP which could be a marker of disease activity.
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PMID:Elevated liver isoenzymes of alkaline phosphatase and disease activity in patients with Crohn's disease. 862 42

Until recently the investigation of serological responses to mycobacteria in patients with Crohn's disease has been hindered by the considerable degree of cross-reactivity between antigens of M. paratuberculosis, and other mycobacterial subspecies. We evaluated the serological response of Crohn's disease patients to a recently identified species-specific 18 kDa protease-resistant antigen corresponding to M. paratuberculosis bacterioferritin. The 18 kDa antigen was purified from M. paratuberculosis as previously described. Serum was obtained from 40 patients with Crohn's disease, 15 with ulcerative colitis, 25 coeliac patients, and 21 normal blood donors. Antibody levels were measured by enzyme-linked immunosorbent assay (ELISA), with anti-human IgA and IgG alkaline phosphatase conjugate. Antibody titres were expressed as the dilution giving 1/3 of the plateau binding value of a standard positive serum (MT/3). Disease activity of the Crohn's disease cases was assessed using the Harvey-Bradshaw index. There was no statistically significant elevation of the mean IgG or IgA MT/3 titres of Crohn's disease patients over controls. No patients had antibody titres greater than two standard deviations above the mean control MT/3 titres, and there was no significant correlation between Crohn's disease activity and level of antibody titres. These findings make it unlikely that M. paratuberculosis is of primary pathogenic importance in Crohn's disease.
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PMID:Antibodies against Mycobacterium paratuberculosis in Crohn's disease. 873 66

Patients with chronic inflammatory bowel diseases (IBD) are at increased risk to develop osteopenia and osteoporosis. New parameters for the assessment of bone formation and especially bone resorption have significantly improved the diagnostic procedures to characterize bone metabolism. Biochemical characterization of bone turnover in IBD patients may provide important information about the pathogenesis of osteoporosis in this patient population. A cross-sectional study was performed. One hundred forty-nine patients (77 men, 52 premenopausal, and 20 postmenopausal women) with IBD (104 with Crohn's disease [CD] and 45 with ulcerative colitis [UC]) underwent clinical, osteodensitometric, and metabolic bone assessment. Bone mineral density was determined by dual energy X-ray absorptiometry. Bone formation (bone alkaline phosphatase), bone resorption (N-terminal telopeptide of type-I collagen, free desoxypyridinoline, total pyridinoline, and desoxypyridinoline), vitamin D, and parathyroid hormone were assessed. Thirty-six percent of patients with CD and 32% with UC showed osteopenia, 15% with CD and 7% with UC showed osteoporosis. Bone resorption was significantly increased in IBD patients compared to normal controls, whereas bone formation did not show a compensatory increase. Bone formation was even more suppressed in the subset of patients currently treated with corticosteroids. Our data confirm the high prevalence of osteopenia and osteoporosis reported in IBD patients. Furthermore, we provide evidence for an increased bone resorption accompanied by low bone formation in IBD patients. This imbalance of bone metabolism is likely to be one of the reasons for increased bone loss in IBD patients.
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PMID:Reduced bone mineral density and unbalanced bone metabolism in patients with inflammatory bowel disease. 983 78

The overlap syndrome between autoimmune hepatitis and primary sclerosing cholangitis is a rare condition and only few cases have been published, partly associated with ulcerative colitis, but not with Crohn's disease. We report an autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome in a female patient with Crohn's disease. In addition, a second case of overlap syndrome is reported in a man without inflammatory bowel disease. A 24-year-old woman was referred with a 10-month history of diarrhoea and biochemical changes including elevated serum levels of alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase and immunoglobulin G. Enzyme linked immunosorbent assay showed that antinuclear autoantibodies were elevated. Immunofluorescence for perinuclear-staining antineutrophil cytoplasmatic antibodies was positive. Diagnostic criteria of definite autoimmune hepatitis according to the International Autoimmune Hepatitis Group were fulfilled. Liver biopsy simultaneously showed criteria of autoimmune hepatitis and primary sclerosing cholangitis. Endoscopic retrograde cholangiography demonstrated features of primary sclerosing cholangitis. Colonoscopy and colonoscopic biopsies indicated an active Crohn's disease affecting the terminal ileum and the ascending and transverse colon. Furthermore, we report the case of a 28-year-old man with known primary sclerosing cholangitis for the previous 6 years, and who developed jaundice and a marked increase of aspartate aminotransferase, alanine aminotransferase and immunoglobulin G, leading to the diagnosis of definite autoimmune hepatitis. A review of the literature revealed only 16 cases of an autoimmune hepatitis/primary sclerosing cholangitis syndrome in patients without inflammatory bowel disease or in association with ulcerative colitis. We report two additional cases, one case showing an association with Crohn's disease.
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PMID:Overlap syndrome between autoimmune hepatitis and primary sclerosing cholangitis in two cases. 1083 1


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