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At least 955 records · Page 53Linked to original sources
PubMed2002

6-MP metabolite profiles provide a biochemical explanation for 6-MP resistance in patients with inflammatory bowel disease.

BACKGROUND & AIMS: Approximately 40% of inflammatory bowel disease (IBD) patients fail to benefit from 6-mercaptopurine (6-MP)/azathioprine (AZA). Recent reports suggest 6-thioguanine nucleotide (6-TGN) levels (>235) independently correlate with remission. An inverse correlation between 6-TGN and thiopurine methyltransferase (TPMT) has been described. The objectives of this study were to determine whether dose escalation optimizes both 6-TGN levels and efficacy in patients failing therapy because of subtherapeutic 6-TGN levels and its effect on TPMT. METHODS: Therapeutic efficacy and adverse events were recorded at baseline and upon reevaluation after dose escalation in 51 IBD patients. 6-MP metabolite levels and TPMT activity were recorded blinded to clinical information. RESULTS: Fourteen of 51 failing 6-MP/AZA at baseline achieved remission upon dose escalation, which coincided with significant rises in 6-TGN levels. Despite increased 6-MP/AZA doses, 37 continued to fail therapy at follow-up. Dose escalation resulted in minor changes in 6-TGN, yet a significant increase in 6-methylmercaptopurine ribonucleotides (6-MMPR) (P < or = 0.01) and 6-MMPR:6-TGN ratio (P < 0.001). 6-MMPR rises were associated with dose-dependent hepatotoxicity in 12 patients (24%). TPMT was not influenced by dose escalation. CONCLUSIONS: Serial metabolite monitoring identifies a novel phenotype of IBD patients resistant to 6-MP/AZA therapy biochemically characterized by suboptimal 6-TGN and preferential 6-MMPR production upon dose escalation.

Adolescent↗
PubMed2002

Screening for osteoporosis in patients with inflammatory bowel disease by using urinary N-telopeptides.

BACKGROUND: Patients with inflammatory bowel disease are at increased risk of osteoporosis. DESIGN AND METHODS: We carried out a prospective study of bone mineral density and biochemical markers of bone metabolism like osteocalcin and urinary N-telopeptides in 72 patients with inflammatory bowel disease and evaluated if one of these markers detects osteoporosis. In addition, bone mineral density and N-telopeptides were analysed retrospectively in a second series of 93 patients with inflammatory bowel disease in order to assess predictive values found in the first patient group in an independent sample. RESULTS: Multiple linear regression showed that N-telopeptides (P < 0.0001) and total white blood cell count (P = 0.006) correlated negatively with the bone mineral density of the lumbar spine and only N-telopeptides (P = 0.005) correlated negatively with the bone mineral density of the femoral neck. Using receiver operator characteristic curves N-telopeptide concentrations of > 40 (30) nmol N-telopeptides/mmol creatinine were chosen as best cut-off values to exclude osteoporosis at the lumbar spine (femoral neck). Using these cut-off values a negative predictive value of 100% (100%) and a positive predictive value of 37.5% (27.9%) were found in the first group, and a negative predictive value of 95.2% (96%) and a positive predictive value of 15.6% (23.3%) in the second, independent group of patients. CONCLUSION: Our data suggest that N-telopeptide levels could be used as a tool for the screening of osteoporosis and for selecting those inflammatory bowel disease patients where bone mineral density measurement is indicated.

Adult↗
PubMed1986

Giant and symptomatic inflammatory polyps of the colon in idiopathic inflammatory bowel disease.

Four cases of giant inflammatory polyps were found in a series of 86 consecutive colectomies for inflammatory bowel disease. Two presented a distinctive clinical syndrome of abdominal pain and chronic iron-deficiency anemia due to blood loss. Secondary ulceration of the heads of the polyps accounted for the bleeding and anemia, and the size of the polyps accounted for the abdominal pain. In both cases unusually long portions of colon were involved by the giant polyps. The third and fourth cases had rare complications--reactivation of an enterocutaneous fistula and perforation of an acquired diverticulum. These cases demonstrate that giant inflammatory polyps may produce symptoms independently of the underlying inflammatory bowel disease. In reported cases of giant inflammatory polyps, approximately two-thirds had Crohn's disease and one-third had ulcerative colitis. The transverse colon was the commonest location, pain was the commonest symptom, and the polyps were localized to a short segment of colon in the majority of cases. More than 50% of cases mimicked neoplasm on barium enema. Giant inflammatory polyps may produce a variety of distinctive signs and symptoms and deserve independent recognition.

Adult↗
PubMed2005

TPMT genotype and the use of thiopurines in paediatric inflammatory bowel disease.

BACKGROUND: Thiopurines are used in the treatment of inflammatory bowel disease. They are metabolised via methylation by thiopurine-S-methyltransferase (TPMT), which displays a genetically determined polymorphic activity. Subjects with reduced TPMT activity have a higher concentration of active thiopurine metabolites and may be at increased risk of bone-marrow suppression. AIMS: To evaluate the relevance of TPMT genotyping in the management of thiopurines therapy in inflammatory bowel disease patients. PATIENTS AND METHODS: Adverse effects and clinical response were determined retrospectively and correlated with TPMT genotype in 70 paediatric inflammatory bowel disease patients. RESULTS: Nineteen patients (27.1%) developed adverse effects; of the 51 who did not, 34 (66.7%) responded to treatment. Five patients (7.1%) were heterozygous for a variant TPMT allele; two of these (40%) were intolerant to thiopurines, compared to 17 of the 65 patients (26.2%) with a wild type gene (O.R. 1.88, 95% CI 0.29-12.2, p=0.61); among the 34 responders, the median dosage of the drug required to obtain remission was lower for mutated than for wild type patients (1.6mgkg(-1)day(-1) versus 2.0mgkg(-1)day(-1), p=0.043). CONCLUSIONS: There was no significant association between adverse effects of thiopurines and TPMT heterozygous genotype, but TPMT genotyping could be useful in establishing the most appropriate dose of thiopurines to start treatment.

Adolescent↗
PubMed2000

Exercise and inflammatory bowel disease: immunological aspects.

Exercise may promote a healthy life, improving functional capacities. Little is known about the effects of physical activity in inflammatory bowel disease. Altered immunity is implicated in the pathogenesis of inflammatory bowel diseases. An acute, albeit transient acute immune response, follows heavy endurance exercise. Epidemiological data support the role of physical activity in lowering the risk of inflammatory bowel disease. Moderate physical exercise (60% VO2max) does not cause significant changes in symptoms, intestinal transit time, and permeability. Neutrophil function appears to be primed at basal conditions with significant activation after exercise. At present, mild exercise can be recommended to patients with quiescent inflammatory bowel disease as well as other chronic diseases such as rheumatoid arthritis, while caution is still needed for active disease patients. Patients with inflammatory bowel disease show a reduced exercise capacity after surgery, especially after extensive resections.

Chronic Disease↗
PubMed2004

Comparative analysis of cell adhesion molecules, cell cycle regulatory proteins, mismatch repair genes, cyclooxygenase-2, and DPC4 in carcinomas arising in inflammatory bowel disease and sporadic colon cancer.

Colon carcinoma arising in inflammatory bowel disease often exhibits aggressive behavior compared to sporadic carcinomas. The rationale for the different biological behaviors of these two groups of tumors is not fully understood. In this study, we have examined carcinomas arising in inflammatory bowel disease (IBD) and sporadic carcinomas (SCA) for molecular differences that may provide clues for the behavioral disparity of these tumors. Thirty-eight colon carcinomas (12 from ulcerative colitis, 5 from Crohn's disease, and 21 SCA) were analyzed by immunohistochemistry for cell adhesion molecules (E-cadherin, beta-catenin, CD44), cell cycle regulatory proteins (cyclin D1, p27, p21), mismatch repair proteins (hMLH1, hMSH2), cyclooxygenase-2 and DPC4. Carcinomas arising in IBD showed significant decrease in expression of cell adhesion molecules, the cell cycle inhibitor protein, p21, and increased expression of cyclooxygenase-2 compared to sporadic carcinomas. No differences were observed in the expression of cell cycle regulatory proteins p27, cyclin D1, DPC4 and mismatch repair proteins between these two groups of tumors. Decreased expression of p21 as well as adhesion molecules may provide increased impetus for the aggressive behavior of tumors arising in inflammatory bowel disease.

Adaptor Proteins, Signal Transducing↗
PubMed1992

Value of endoscopic ultrasonography in the assessment of inflammatory bowel diseases.

The value of EUS in the assessment of inflammatory bowel diseases was determined. EUS was useful for estimation of the histological changes of inflammatory bowel diseases. In ulcerative colitis, EUS findings were classified into five types, which correlated with the colonoscopic and histological findings. Studies in surgical cases and further prospective investigations are necessary, however, to determine whether EUS can contribute to the management of inflammatory bowel diseases.

Adult↗
PubMed1991

Polypoid and pseudopolypoid manifestations of inflammatory bowel disease.

The polypoid manifestations of the idiopathic inflammatory bowel diseases (ulcerative colitis and Crohn disease) are often confusing. Inflammatory polyps project above the level of the surrounding mucosa. Pseudopolyposis (in ulcerative colitis) or a cobblestone appearance (in Crohn disease) results when extensive ulceration develops and only scattered islands of relatively normal mucosa remain; thus, the ulcerated areas may be falsely perceived as the baseline and the islands as polyps. Postinflammatory (filiform) polyps--fingerlike projections of submucosa covered by mucosa on all sides--reflect healing of undermined mucosal and submucosal remnants and ulcers and are almost always multiple. Patients with ulcerative colitis or Crohn disease are at increased risk for developing adenocarcinoma. Occasionally, dysplasia occurs as a polypoid lesion. Dysplasia of the colon (mucosal atypia) is a histologic marker highly associated with adenocarcinoma. Because differentiating adenocarcinoma and dysplasia from inflammatory or postinflammatory polyps is sometimes difficult or impossible, endoscopy and biopsy are usually recommended for definitive diagnosis of suspicious lesions.

Adolescent↗
PubMed1990

Occupational distribution of inflammatory bowel disease among German employees.

Previous reports have shown that both Crohn's disease and ulcerative colitis affect people in white collar occupations associated with higher income and higher social class more frequently than other groups in the population. This study sought to carry these analyses one step further and investigate the distribution of inflammatory bowel disease by individual occupations. The German social security statistics for 'rehabilitation' were used to assess the occupational distribution of Crohn's disease and ulcerative colitis. From 1982 to 1988, a total of 12,014 people were granted rehabilitation as a result of inflammatory bowel disease. Low male prevalence of inflammatory bowel disease was found among bricklayers, road construction workers, unskilled workers in brick and stone, unskilled labourers, and security personnel. Low rates were found among women employed in cleaning and maintenance, and in those without occupation. In contrast, a high male prevalence was found among instrument makers, electricians, bakers, and technical assistants. Among female employees, inflammatory bowel disease was significantly associated with sales representatives, office workers, health occupations, and hairdressers. These associations were found in the complete data for 1982-8 as well as in the separate data for the two half periods 1982-5 and 1986-8. Highly significant correlations between the occupational distribution of Crohn's disease and ulcerative colitis were found among both male and female employees. It seems that occupations involving work in the open air and physical exercise are protective, while being exposed to air conditioned artificial working conditions or extended and irregular shift working confer a risk of contracting inflammatory bowel disease.

Colitis, Ulcerative↗
PubMed1998

Detection of pro- and anti-inflammatory cytokines in stools of patients with inflammatory bowel disease.

BACKGROUND: Cytokines play a predominant role in immune and inflammatory reactions in inflammatory bowel disease. Any cytokine that is produced locally as a result of gut inflammation may leak into the bowel lumen and appear in the stools. We examined the usefulness of determining cytokine profiles in the stools of patients with ulcerative colitis or Crohn's disease. METHODS: Cytokine concentrations in stool extracts were measured in 36 patients with ulcerative colitis, 32 patients with Crohn's disease, 9 controls with inflammatory disease, and 18 normal controls by means of enzyme-linked immunosorbent assays. RESULTS: Stool concentrations of interleukin-1beta and interleukin-1 receptor antagonist in patients with active inflammatory bowel disease increased significantly and correlated with various inflammatory factors and stool concentrations of polymorphonuclear cell elastase. The ratio of interleukin-1 receptor antagonist to interleukin-1beta in active disease was reduced significantly compared with that in inactive disease or in normal controls. Paired analysis showed a decrease in tumor necrosis factor-alpha and interleukin-1beta and interleukin-1 receptor antagonist and an increase in interleukin-4 and interleukin-10 concentrations after the resolution of disease exacerbation. CONCLUSIONS: Measurement of cytokines in stools may be a useful and noninvasive means of understanding pathophysiology and clinical monitoring in inflammatory bowel disease.

Adult↗
PubMedDate not supplied

[De novo inflammatory bowel diseases after liver transplantation: description of four new cases and a review of the literature].

Inflammatory bowel diseases are a result of an aberrant mucosal immune response to gut microflora. Several groups have reported newly diagnosed inflammatory bowel diseases following solid organ transplantation and subsequent immunosuppressive therapy. We describe four cases of newly diagnosed inflammatory bowel diseases following liver transplantation in a pool of 120 transplanted patients. These patients had no prior history of inflammatory bowel diseases or primary sclerosing cholangitis and were immunosuppressed. Two patients were transplanted for a hepatitis C related cirrhosis, one for alcoholic cirrhosis and one patient for autoimmune cirrhosis. Three patients were diagnosed with ulcerative colitis and one with Crohn's disease. These four patients were on a cyclosporin monotherapy when their inflammatory bowel diseases were diagnosed. These data suggest that cyclosporin monotherapy following solid organ transplantation does not prevent development of inflammatory bowel diseases.

Adult↗
PubMed1992

Familial inflammatory bowel disease in a paediatric population.

Familial aspects of inflammatory bowel disease (IBD) were assessed as part of an age and sex matched case control study of 91 children with IBD and 131 controls. The prevalence of IBD in family members of the children was studied, the affected side (mother's side or father's side) of the family was documented and the type of inflammatory bowel disease was traced among relatives. Data were collected from children in out-patient clinics at a large urban tertiary-care facility. All family data were verified with the affected relatives and/or their physicians. The children with IBD (the cases) had significantly (P = 0.0000385) more IBD in their families than the controls. Among all children with IBD in their family, IBD was found significantly (P = 0.0073) more often on the mother's side of the family than on the father's side. Patterns of disease varied within families. A mixture of ulcerative colitis and Crohn's disease was found within families. The implications of the findings are discussed. Directions for prevention, screening, early intervention and further study are given.

Adolescent↗
PubMed2006

Respiratory symptoms in patients with inflammatory bowel disease and the impact of dietary salicylates.

BACKGROUND: Respiratory symptoms are over-represented in inflammatory bowel disease. There are similarities between the epidemiology of inflammatory bowel disease and that of respiratory conditions for which an adverse influence of salicylate has been identified. Natural salicylates exist within our diet. AIMS: To determine whether a lower intake of dietary salicylates is associated with less active inflammatory bowel disease and fewer concurrent respiratory symptoms. PATIENTS AND METHODS: Respiratory status, inflammatory bowel disease activity, quality of life, and dietary habits were established in 73 patients with Crohn's disease and 69 with ulcerative colitis, using a self-administered questionnaire and peak expiratory flow rate readings. Harvey-Bradshaw and Simple Birmingham/Royal Free Colitis indices, an internally validated respiratory score, and estimated weekly dietary salicylate intake, were calculated for each patient. RESULTS: There was at least one respiratory symptom in 63.4% of patients. The commonest underlying respiratory diagnosis was asthma. Respiratory impairment was similar in ulcerative colitis and Crohn's disease; 56.3% of Crohn's disease patients with an active respiratory diagnosis had other extra-intestinal manifestations. The dietary salicylate intake was independent of respiratory status, but inversely correlated with ulcerative colitis activity (dietary salicylate intake 37.0mg versus 21.4mg for low and higher Simple Birmingham/Royal Free Colitis index, respectively; p<0.02). A similar association was not seen in Crohn's disease. CONCLUSIONS: Respiratory impairment is common in inflammatory bowel disease. Higher intake of dietary salicylates is associated with less active colitis and possibly causally so.

Adolescent↗
PubMed2005

The leukocyte count predicts the efficacy of treatment with azathioprine in inflammatory bowel disease.

INTRODUCTION: Azathioprine has variable efficacy in inflammatory bowel disease. Previous studies suggested that either neutropenia, an increase in the mean corpuscular volume, the assessment of thiopurine methyl-transferase activity or erythrocyte 6-thioguanine values might predict the treatment response. However, due to the conflicting results of the preceding studies there are yet no established laboratory values which allow an estimation of the clinical response. PATIENTS AND METHODS: 45 patients with Crohn's disease and 39 patients with ulcerative colitis were enrolled in this retrospective evaluation. After a minimum of six months therapy with azathioprine patients in remission were compared with those who did not achieve a stable remission with respect to the number of leucocytes, lymphocytes, neutrophil granulocytes and the mean corpuscular volume. RESULTS: Patients who went into remission during treatment with azathioprine displayed significantly lower leukocyte counts if compared to patients who were not in remission (p = 0.004 in Crohn's disease and 0.003 in ulcerative colitis). A similar tendency was also observed with respect to the granulocyte count (p = 0.007 in Crohn's disease and 0.004 in ulcerative colitis). The mean corpuscular volume did not correlate with the response to purine analogues. DISCUSSION: The absolute leukocyte count and the percentage of granulocytes seem to predict the response to purine analogues in inflammatory bowel disease and possibly offers a feasible and cost effective diagnostic tool for the assessment of therapeutic efficacy. Subsequent preferably prospective studies should aim to define the optimal cut-off value for the leukocyte count.

Adult↗
PubMedDate not supplied

Quality of life in inflammatory bowel disease.

The usual indices of activity of Inflammatory Bowel Disease fail to evaluate an important aspect of patients' status, their Quality of Life (QOL). A questionnaire dealing with four important aspects of QOL (intestinal and systemic symptoms, emotional and social function) was developed and validated. The questionnaire was administered to 72 healthy controls, 57 patients with Ulcerative Colitis and 55 with Crohn's Disease with different disease severity. Compared to controls, QOL was impaired not only in the more severe forms of disease, but also in patients in remission. In Crohn's Disease, QOL was not closely correlated with the clinical features, thus indicating that the impairment of QOL cannot be inferred from the clinical status and that patients do not "adapt" with the passing of time. The questionnaire allows a more comprehensive definition of the patients' state of health, identifying features which might be underestimated as they fail to emerge from the routine clinical evaluation. A tool of this kind could be used alongside the activity index of disease, both in clinical studies and during routine follow-up.

Adaptation, Psychological↗
PubMed1999

Inflammatory bowel disease approaching the 3rd millennium: pathogenesis and therapeutic implications?

The aetiology of inflammatory bowel disease remains unknown, but genetic, immuno-inflammatory, infectious, vascular and neural factors play an important role. All effective treatments in use today were introduced empirically and most have multiple action. Targeted therapy is very attractive, either with cell and gene therapy or by using specific cytokine inhibitors and inhibitory cytokines. The role of the intestinal milieu, and enteric flora in particular, appears to have a much greater significance than previously appreciated. The reduction of any changes leading to pro-coagulant activity may be a promising line of therapeutic investigation, and measures to reduce platelet aggregation and endothelial cell adhesiveness are examples of therapeutic potentials. Finally, there has been tangible demonstration of the ability of nerves to alter the inflammatory process which will lead to new therapeutic approaches in inflammatory bowel disease.

Colitis, Ulcerative↗
PubMed2003

Gelatinase A (MMP-2), collagenase-2 (MMP-8), and laminin-5 gamma2-chain expression in murine inflammatory bowel disease (ulcerative colitis).

Dextran sulfate sodium-induced inflammatory bowel disease in mice resembles human ulcerative colitis. In inflammatory bowel diseases matrix metalloproteinases contribute to tissue degradation. Laminin-5 is an anchoring filament protein in the basement membrane area that can be cleaved by matrix metalloproteinases. We investigated the expression of matrix metalloproteinases-2 and -8 and laminin-5 gamma2-chain in dextran sulfate sodium-induced mice by immunohistochemistry and in situ hybridization. Matrix metalloproteinase-8 expression was evidenced in the colon surface epithelial cells and the protein was more abundant in dextran sulfate sodium-induced mice colon. Matrix metallproteinase-2 and laminin-5 gamma2-chain colocalized in the colon surface epithelial cells and in the basement membrane zone as demonstrated by double immunostaining. In dextran sulfate sodium-induced colon, matrix metalloproteinase-2 immunoreactivity was detected in epithelial cells in the lower parts of the crypt and surrounding the degraded crypts. Matrix metalloproteinase-2 and -8 could participate in the local epithelial inflammatory processes and tissue destruction. The presence of laminin-5 gamma2-chain indicates alternative anchoring mechanisms in the colon, a compartment devoid of hemidesmosomes.

Animals↗
PubMed2006

Advances in the molecular dissection of inflammatory bowel disease.

Recent advances in the field of inflammatory bowel disease (IBD) genetics have enabled the definition and refinement of multiple IBD susceptibility loci and the identification of gene variants within such regions showing association with Crohn's disease (CD) and/or ulcerative colitis (UC). Most notable among the newly defined genetic determinants of IBD are specific variants in the CARD15 gene, which have been shown widely to influence both susceptibility and phenotype in CD. These genetic data have inspired intensive studies of CARD15 biologic functions and the information emerging from these analyses has already substantively enhanced understanding of the signaling pathways coupling bacterial pathogens to the host immune response. Genetic data implicating various other signaling effectors in IBD susceptibility have similarly focused attention on the molecular pathways driven or regulated by these proteins and the biochemical events linking effector/pathway dysfunction to intestinal inflammation and disease. In this review, progress in defining the genetic determinants of IBD is described with an emphasis on the impact of such knowledge on understanding of IBD molecular pathophysiology.

Animals↗