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Quality of life in Korean patients with inflammatory bowel diseases: ulcerative colitis, Crohn's disease and intestinal Behçet's disease.

Health-related quality of life (HRQOL) is an important outcome factor in chronic diseases such as inflammatory bowel disease (IBD). This study used the Korean translation of the disease-specific, self-administered Inflammatory Bowel Disease Questionnaire (IBDQ) to compare HRQOL in ulcerative colitis (UC; n = 98), Crohn's disease (CD; n = 49), and intestinal Behçet's disease (BD; n = 34). In addition to the current status, patients were asked retrospectively to recall their symptoms at the beginning and during the worst period of their disease. Disease activity was measured by St. Mark's Activity Index, Crohn's disease Activity Index (CDAI), and the Harvey-Bradshaw Index (HBI). In all IBD patients, including those with BD, the IBDQ total score during the worst period was significantly lower than that at present and that at the beginning of the disease. However, there were no significant differences between groups regarding the total IBDQ score or its various dimensions. In UC a strong correlation between IBDQ scores and St. Mark's Activity Index was observed (r = -0.708, P < 0.001). IBDQ scores were also highly correlated with CDAI and HBI in both CD (r = -0.506, P < 0.001 for CDAI; r = -0.600, P < 0.001 for HBI) and BD (r = -0.687, P < 0.001 for CDAI; r = -0.531, P < 0.001 for HBI). However, the current IBDQ score was not related to demographic parameters such as gender, age, educational status, economic status, and marital status as well as disease factors such as duration of disease, history of operation or hospital admission, extent of disease in UC, involved region in CD, and clinical type in BD. We conclude that the Korean IBDQ is a responsive and promising instrument for measuring HRQOL of IBD patients in clinical trials. In addition, the IBDQ can be helpful in developing a disease-specific activity index in BD.

Adolescent↗

Growth hormone in inflammatory bowel disease.

Crohn's disease and ulcerative colitis are inflammatory diseases of the gastrointestinal tract characterized by chronic relapsing inflammation and catabolism. Growth hormone/insulin-like growth factor-I axis is important in inflammatory bowel disease, because of the effects on epithelial cell kinetics, collagen deposition and immunomodulation. The potential of growth hormone as a therapeutic option in inflammatory bowel disease has been proven in various clinical settings. Acquired growth hormone resistance in inflammatory bowel disease seems to be mediated by a combination of undernutrition and active inflammation. In particular, proinflammatory cytokines, such as TNF-a and interleukin-6, have been implicated as potential mediators of growth hormone resistance. The introduction of anti-TNF-alpha monoclonal antibodies has proven very efficacious in patients with inflammatory bowel disease. By reducing cytokines levels in inflammatory cells of intestinal mucosa, infliximab could interfere with cytokine-induced growth hormone resistance. Recent in vivo data have shown that acquired growth hormone resistance in patients with inflammatory bowel disease may be reversed after the administration of anti-TNF-alpha therapy.

Animals↗

Antigen transport and cytoskeletal characteristics of a distinct enterocyte population in inflammatory bowel diseases.

Intestinal antigen uptake is enhanced in inflammatory bowel disease. We analyzed transcellular transport routes of antigens in different compartments of normal enterocytes and atypical intestinal epithelial cells called "rapid antigen uptake into the cytosol enterocytes" (RACE cells). These cells constitute a recently described population of enterocyte-derived cells, which are increased in inflammatory bowel disease. Mucosa of freshly resected specimens were incubated with the antigens ovalbumin or horseradish peroxidase. Ultrastructural labeling patterns of differentiation-dependent proteins, the brush-border enzyme sucrase-isomaltase and the cytoskeleton proteins villin and actin, were determined in enterocytes. Apoptosis was investigated biochemically and ultrastructurally by cleavage of caspase-3. Both antigens were transported to late endosomes and to trans-Golgi vesicles of enterocytes in inflammatory bowel disease and control specimens. Quantitative evaluation revealed a significantly increased transepithelial antigen transport in both compartments of RACE relative to normal enterocytes. Labeling densities for sucrase-isomaltase, villin, and actin were decreased in RACE relative to normal enterocytes. Caspase-3 was not increased in RACE cells relative to controls. RACE cells are characterized by increased antigen transport to late endosomes and the trans-Golgi network, a disassembled cytoskeleton and lower concentrations of proteins that are markers of cell differentiation.

Actins↗

The impact of helical computed tomography on the diagnosis of unsuspected inflammatory bowel disease in the large bowel.

Inflammatory bowel diseases (IBD) are diagnoses that can be easily overlooked clinically. The aim of this study was to investigate if CT is able to make a contribution to the identification of previously unsuspected cases of IBD. We retrospectively identified cases in which the possibility of an IBD was raised in CT reports (over a 4-year period), by utilising a keyword search of the radiology database. Cases with a previously known or suspected IBD were rigorously excluded by review of case notes, and endoscopic, radiological, histological and microbiological findings. The CT images of the identified cases were reviewed by a blinded observer to document the extent of bowel wall thickening, the location of lesion(s), and presence of peri-colic fat abnormality, ascites and/or collections. The observer also attempted to corroborate the presence, and to identify the type, of IBD based on the CT appearances alone. Thirty-five cases (out of approximately 19,000 body CTs performed) of clinically unsuspected IBD were identified, of which 27 underwent further investigation. An IBD was confirmed in 48% (13 of 27): Crohn's disease (n=6), ulcerative colitis (n=2), pseudomembranous colitis (n=3) and other (n=2), of which 70% (9 of 13) were correctly typed by the reviewer. Inflammatory bowel disease was not substantiated in the remainder (14 of 27), although 7 of these had other bowel pathologies: diverticular disease (n=4); and carcinoma (n=3). Prospectively determining the presence, and furthermore type, of IBD on CT is challenging largely because of the considerable overlap in the appearances of the individual IBDs and indeed of normality. Nevertheless, CT is able to identify clinically unsuspected cases and radiologists should be alert to this treatable and not infrequently elusive diagnosis.

Adult↗

Frequency of extraintestinal manifestations in patients with inflammatory bowel disease in Northwest Greece and review of the literature.

BACKGROUND: Inflammatory bowel disease mainly affects the bowel but also has extraintestinal manifestations. AIMS: To report the frequency of extraintestinal manifestations in patients with inflammatory bowel disease in Northwest Greece. PATIENTS; The data files of 256 inflammatory bowel disease patients (diagnosis between 1983-19971 were analysed. METHODS: Retrospective investigation of patient files. RESULTS: In patients with ulcerative colitis: 13.9% (30/215) had developed skin manifestations, 6% (13/215) had kidney stones, 1.39% (3/215) had iridocyclitis, 1.86% (4/215) had primary sclerosing cholangitis, 4.18% (9/215) had sacroiliitis, 8.31% (18/215) had peripheral arthalgias, 2.3% (5/215) had colitic arthritis and finally 1.39% (3/215) had deep vein thrombosis). In patients with Crohn's disease: 24.3% (9/37) had developed skin manifestations, 5.4% (2/37) had kidney stones, 2.7% (1/37) had iridocyclitis, 16.2% (6/37) had sacroiliitis, 8.1% (3/37) had peripheral arthralgias, 5.4% (2/37) had colitic arthritis and, finally, 8.1% (3/37) had deep vein thrombosis. Sacroiliitis (p = 0.01), deep vein thrombosis (p = 0.04) and erythmema nodosum (p = 0.01) were more common in patients with Crohn's disease. CONCLUSIONS: Extraintestinal manifestations are not rare in patients with inflammatory bowel disease, especially in Crohn's disease patients, in our area, but have, generally, a mild profile.

Adult↗

Review article: psychosocial factors in the quality of life of patients with inflammatory bowel disease.

Information on quality of life in inflammatory bowel disease is limited. Despite the clear importance of this topic to patients, quality of life measurement is seldom undertaken in day-to-day management of patients or included in clinical trials. Although previous reviews have dealt with quality of life, the area of psychosocial functioning has not been specifically addressed. The aim of this study was to review the psychosocial factors affecting quality of life in patients with inflammatory bowel disease, using an electronic search of MEDLINE, EMBASE, CINAHL and psycINFO. Of the 751 articles identified by the search, 107 were considered relevant and included in the review. A number of psychosocial factors appear to be important, including gender, socioeconomic status, ethnicity and perceived stress. To improve the quality of life in patients with inflammatory bowel disease, clinicians' attention needs to be drawn towards this subject, with an awareness of those patient groups more vulnerable to impaired quality of life. These identified variables also represent important factors, which should be adjusted for when conducting research into quality of life in these patients.

Adaptation, Psychological↗

Impairment of health-related quality of life in patients with inflammatory bowel disease: a Spanish multicenter study.

BACKGROUND: Inflammatory bowel disease impairs patients' perception of health and has a negative impact on health-related quality of life (HRQOL). Most studies include patients from a single hospital. This may bias limit results through the use of small patient samples and/or samples within a restricted disease spectrum. METHODS: HRQOL was measured in patients with ulcerative colitis (UC) and Crohn's disease (CD) from 9 hospitals located in different geographical areas in Spain using 2 questionnaires: the Spanish version of the Inflammatory Bowel Disease Questionnaire (IBDQ) and the EuroQol. Results are expressed as medians. RESULTS: The study included 1156 patients (528 patients with UC and 628 with CD; median age, 35 yr; slight predominance of women, 617 versus 539). HRQOL worsened in parallel with disease severity to a similar extent in both UC (IBDQ scores of 6.1, 4.7, and 4.0 for the 3 disease severity groups, respectively) and CD (IBDQ scores of 6.1, 5.0, and 4.1, respectively). A similar inverse relation between clinical activity and quality of life was observed when EuroQol preference values were used. All 5 dimensions of the IBDQ showed significantly lower scores in patients with active UC and CD than in patients in remission. The pattern of scores by IBDQ dimensions differed between patients in relapse (who scored worse on the digestive symptoms dimension) and patients in remission. Variables related with disease activity, time of evolution since diagnosis and female sex, were significantly associated with having a worse perception of HRQOL. The type of disease or geographical area of residence did not influence results on the IBDQ. CONCLUSIONS: UC and CD impair patients' HRQOL, and the degree of impairment depends on disease activity but is independent of the type of disease and place of residence.

Adult↗

Pro-inflammatory signaling by Jun-N-terminal kinase in inflammatory bowel disease.

Since Jun-N-terminal kinase participates in intracellular signaling cascades resulting in inflammatory responses, inhibiting this pathway may represent a new treatment for inflammatory bowel disease including ulcerative colitis and Crohn's disease. However, the functional significance of the activation of this kinase in inflammatory bowel disease remains unclear. We investigated whether Jun-N-terminal kinase activation is increased in inflammatory bowel disease and analyzed the effects of SP600125, which decreases inflammatory cytokine synthesis by inhibiting the phosphorylation of this kinase. Phosphorylation of the kinase was examined in affected human colon using an enzyme-linked immunosorbent assay and immunohistochemistry. The effect of SP600125 on cytokine production was examined in cultures of patients' leukocytes and colonic tissue. Finally, rats received injection of SP600125 (30 mg/kg, s.c.) or vehicle twice daily 2 h before the induction of colitis with dextran sulfate sodium. SP600125 effects were determined observationally and histologically. Colonic tissue contained increased phosphorylated kinase in patients with inflammatory bowel disease with expression localized to the nucleus of epithelial and lamina propria mononuclear cells in lesions. Culturing mononuclear cells or colonic tissue with SP600125 down-regulated inflammatory cytokine production. Prophylactic treatment with SP600125 significantly reduced clinical and pathological scores in dextran sulfate sodium-treated rats. This first demonstration of the pathogenetic role of Jun-N-terminal kinase in the development of intestinal inflammation suggests that inhibiting its phosphorylation could benefit patients with inflammatory bowel disease.

Animals↗

Ultrasound demonstration of bowel wall thickness in inflammatory bowel disease.

Twenty-eight patients with inflammatory bowel disease were examined with ultrasound. When possible, maximum bowel wall thickness was measured and the site of any focal abnormality recorded. There were 19 patients with Crohn's disease and nine with ulcerative colitis. Bowel wall thickness ranged from 0.5-1.8 mm in the Crohn's group to 0.3-0.8 cm in the ulcerative colitis group. Following treatment, a measurable reduction in bowel wall thickness was demonstrated in 13 of the patients with Crohn's disease. No significant change in bowel wall thickness was detected in five of the patients with ulcerative colitis. The results echo the findings at double-contrast radiography and suggest a possible role for ultrasound in the assessment and follow-up of inflammatory bowel disease.

Colitis, Ulcerative↗

[Validation of the German version of the Inflammatory Bowel Disease Questionnaire (Competence Network IBD, IBDQ-D)].

The Inflammatory Bowel Disease Questionnaire (IBDQ) is the standard disease-specific instrument for assessment of health-related quality of life (HRQOL) in patients with inflammatory bowel diseases (IBD). A German translation has not been validated. 415 outpatient IBD-patients (Crohn's Disease n = 306, Ulcerative Colitis n = 109) completed the German version of the IBDQ (Competence network IBD, IBDQ-D), the Hospital Anxiety and Depression Scale German Version (HADS-D) and the Questions on Life Satisfaction FLZ. Face validity was assessed by a physicians' and patients' panel. Disease activity was measured by the German Inflammatory Bowel Disease Activity Index (GIBDI). With 97.3 % completed items the acceptance was high. The Cronbach's alpha for the subscales ranged from 0.88 to 0.89. The correlation coefficients with comparable subscales of other instruments ranged between 0.09 and 0.70. Patients in remission and different disease activities differed significantly (p < 0.001) in all IBDQ-D-subscales.

Adult↗

The CC chemokine receptor 5 delta32 mutation is not associated with inflammatory bowel disease (IBD) in NE England.

Inflammatory bowel disease (IBD) is a group of chronic inflammatory diseases of the gastrointestinal tract of unknown aetiology. Evidence of abnormalities in immune regulation and cytokine production in patients with IBD has led to investigations of various immuno-regulatory genes as potential candidate susceptibility loci. Studies using whole genome scanning have highlighted chromosomes 3, 7, 12 and 16. A 32 base-pair deletion in the CC-chemokine receptor-5 gene (CCR5-A32, chromosome 3p21.3) has been associated with susceptibility to IBD. We have investigated CCR5 as a candidate susceptibility gene in 350 patients (251 with ulcerative colitis and 99 with Crohn's disease) and 103 controls using polymerase chain reaction. There were no significant differences in the distribution of CCR5 genotypes or frequencies comparing patients and controls, or associations with extent of colitis. In contrast to preliminary data, these findings suggest no evidence for involvement of this mutation in susceptibility/resistance or disease progression in IBD.

Colitis, Ulcerative↗

Reduced bone formation in patients with osteoporosis associated with inflammatory bowel disease.

The pathophysiology of bone loss associated with inflammatory bowel disease has not been clearly defined. In this study we have performed a detailed histomorphometric analysis of iliac crest bone obtained from 19 patients with inflammatory bowel disease in whom a diagnosis of osteoporosis had been made. Eleven subjects were receiving prednisolone at the time of their biopsy. Comparison with control values demonstrated a highly significant reduction in trabecular bone area in the patient group (p < 0.001). Wall width, adjusted appositional rate and bone formation rate were all significantly reduced in the patient group (p < 0.001) and the formation period was significantly increased (p < 0.001). Resorption cavities were slightly smaller in the patient group, differences in maximum cavity depth and cavity length achieving statistical significance (p < 0.005 and p < 0.05 respectively). The mineral appositional rate was significantly reduced in the patients with inflammatory bowel disease (p < 0.001) and the mineralization lag time significantly increased (p < 0.001); however, osteoid area, perimeter and seam width were not significantly different from controls. These results demonstrate that osteoporosis associated with inflammatory bowel disease is characterized by reduced bone formation at the cellular and tissue level; the proportionately greater change in wall width than in resorption cavity depth is consistent with a negative remodelling balance. Although none of the patients had osteomalacia as defined by the criteria of increased osteoid seam width and mineralization lag time, the higher mineralization lag time in the patient group indicates a mild mineralization defect.

Adult↗

Data management of an inflammatory bowel disease registry.

The history and etiology of inflammatory bowel disease which is characterized by two major disease processes: ulcerative colitis and Crohn's disease, remain unknown. Research is focussing on seven major areas of genetic, environmental and physiologic factors that apparently relate to this disease. Based on this background, a population based Inflammatory Bowel Disease Registry was established in 1987 in the Lehigh Valley area of southeastern Pennsylvania. Consent forms, patient data forms and protocols for operation and implementation were developed, and databases were designed to accommodate demographic, basic history, follow-up and relative history data. The databases were correlated with an IBD registry ID number which both enabled relational analyses and ensured confidentiality of data information. The registry continues to grow, providing feedback for both continued medical research and supportive information for IBD patients and their physicians.

Database Management Systems↗

Psychological distress, social support, and disease activity in patients with inflammatory bowel disease.

OBJECTIVES: The objectives of this study were to compare the psychological status of patients in active and inactive disease states, to assess social support, and to identify correlates of psychological distress in patients with inflammatory bowel disease (IBD). METHODS: This cross-sectional study was conducted in 200 patients (mean age 36.7 yr [SD = 14.8], 119 [59.5%] female) with long-standing IBD who were seen in tertiary care. Psychosocial assessments included psychological distress (Symptom Checklist-90R), social support (Social Support Questionnaire-6), perceived stress (Perceived Stress Scale-10), and recent minor stressful events (Weekly Stress Inventory). Disease activity was assessed with the Harvey Bradshaw Index. RESULTS: Patients reported higher levels of satisfaction with social support and smaller network sizes compared with normative values. Using multiple linear regression, the independent correlates of psychological distress (p = 0.0001; adjusted R2 = 0.62) were as follows: active disease (p = 0.0234), less time since diagnosis (p = 0.0012), and greater number (p = 0.0001) and impact of stressful events (p = 0.0003). A statistically significant interaction term (p = 0.0171) revealed that the relationship between psychological distress and perceived stress changes depending on the level of satisfaction with social support. For patients with low levels of perceived stress, satisfaction with social support did not affect levels of psychological distress. However, for patients who experienced moderate to high levels of perceived stress, high satisfaction with social support decreased the level of psychological distress. CONCLUSIONS: These findings suggest that strategies aimed at improving social support can have a favorable impact on psychological distress and, ultimately, can improve health outcomes in patients with IBD.

Adult↗

Quality of life issues in patients with inflammatory bowel disease.

The assessment of health-related quality of life (HRQOL) plays an increasingly important role in the evaluation of therapeutic interventions in various chronic diseases, including inflammatory bowel disease (IBD). There are three main types of HRQOL instruments, each of which have specific strengths and limitations. Global assessments provide a general impression of the patient's HRQOL, but they do not identify specific domains of dysfunction. Generic instruments can be used to show similarities or differences among groups or populations, but they may not be sensitive to changes over time or after treatment in groups of patients with specific diseases. Disease-specific instruments, which are derived from and validated in particular disease groups, are the most sensitive indicators of change in HRQOL over time or with treatment. There are several potential sources of bias in HRQOL measurement, and certain instruments are more or less sensitive and reliable than others in detecting impaired function in patients with IBD. Despite differences between studies regarding specific HRQOL findings, as a group, these assessments confirm that HRQOL can be impaired significantly in patients with IBD. Reliable validated HRQOL instruments should be applied with the same methodological rigor as other assessments in clinical trials of different therapeutic strategies for patients with IBD.

Humans↗

Chemokines in inflammatory bowel disease.

Ulcerative colitis (UC) and Crohn's disease (CD), collectively termed inflammatory bowel diseases (IBD), represent chronic relapsing and remitting inflammatory disorders of the gastrointestinal tract that are characterized by leukocytic infiltration of the intestinal mucosa and submucosa. In CD, the inflammation is transmural and frequently associated with granuloma formation. Chemokines have emerged as the most important regulators of leukocyte trafficking during infection or inflammation and, therefore, have been implicated in the pathogenesis of IBD. In this review, recent advances on the role of chemokines and their receptors in mucosal immunity and inflammation are discussed, and the potential use of chemokine/chemokine-receptor antagonists as novel therapeutic targets for the treatment of human IBD is highlighted.

Cell Movement↗

Discovering the cause of inflammatory bowel disease: lessons from animal models.

The precise cause of inflammatory bowel disease remains unclear. Relevant animal models are important tools for studying the underlying mechanisms of inflammation and disease pathogenesis. The purpose of this review is to summarize the various types of animal models available for use in inflammatory bowel disease research and to illustrate how these models have contributed to a better understanding of the etiopathogenesis of inflammatory bowel disease, particularly focusing on papers published during calendar year 1999. Studies using appropriate animal models have provided important discoveries in this field of investigation. These include determination of the key role that pathogenic and regulatory T cells, proinflammatory and immunoregulatory cytokines, indigenous bacterial flora, and putative predisposing genes play in the disease process. The availability of new animal models that closely resemble the human disease is expected to allow further characterization of the initiating event(s) in inflammatory bowel disease and lead to a possible cure for this devastating disease.

Journal Article↗

Bone mineral density and calcium regulating hormones in patients with inflammatory bowel disease (Crohn's disease and ulcerative colitis).

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)

Adult↗