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PubMed1996

Increased expression of keratinocyte growth factor messenger RNA associated with inflammatory bowel disease.

BACKGROUND & AIMS: Alterations in intestinal epithelial cell function are common in inflammatory bowel disease (IBD). Keratinocyte growth factor (KGF) is an epithelial cell-specific mitogen. The aim of this study was to examine IBD tissue for altered KGF expression. METHODS: Expression levels of the KGF and KGF receptor transcripts were analyzed by ribonuclease protection assay. The cellular localization of each transcript was determined using in situ hybridization. RESULTS: KGF messenger RNA levels were increased in inflamed IBD tissue in comparison with control tissues. In normal tissue, KGF messenger RNA was localized to the mesenchymal cells at the tip of the villi in the small intestine and directly underlying the mature enterocytes in the colon, whereas in IBD it was present throughout the lamina propria, although distinct from the germinal centers. The topographic distribution of the KGF in situ hybridization signal in IBD was similar to that observed for T lymphocytes. In contrast, KGF receptor transcripts were localized to the cryptal region of the mucosal epithelium in both normal and IBD tissue, with no apparent differences in the level of expression. CONCLUSIONS: The increased expression of KGF in IBD suggests that it may be involved in mediating the altered regulatory functions of intestinal epithelial cells in this disease.

Colon↗
PubMed2003

Inflammatory bowel disease and the risk of fracture.

BACKGROUND & AIMS: Although patients with inflammatory bowel disease (IBD) have reduced bone mass, there is controversy whether there is an increased risk of fracture. This study examines the risk of fracture and its predictors in patients with IBD. METHODS: In a primary care- based nested case-control study, 231,778 fracture cases and 231,778 age- and sex-matched controls were recruited. A history of IBD was assessed from medical records. RESULTS: The prevalence of IBD was 156 and 282 per 100,000 for Crohn's disease (CD) and ulcerative colitis (UC), respectively. Patients with IBD had an increased risk of vertebral fracture (odds ratio [OR], 1.72; 95% confidence interval [CI], 1.13-2.61) and hip fracture (OR, 1.59; 95% CI, 1.14-2.23). The risk of hip fracture was greater in patients with CD (OR, 1.86; 95% CI, 1.08-3.21) compared with UC (OR, 1.40; 95% CI, 0.92-2.13). Disease severity, assessed by the number of symptoms, predicted fracture even after adjusting for corticosteroid use (OR, 1.46; 95% CI, 1.04-2.04). Only 13% of patients with IBD who had already sustained a fracture were on any form of antifracture treatment. CONCLUSIONS: Patients with IBD have a higher risk of fracture due to both disease activity and use of oral corticosteroids. However, few of these patients are receiving optimal bone-sparing therapy, highlighting the importance of increasing awareness of osteoporosis in those managing these patients.

Adrenal Cortex Hormones↗
PubMed2004

Hyperexpression of inducible costimulator and its contribution on lamina propria T cells in inflammatory bowel disease.

BACKGROUND & AIMS: To investigate the role of inducible costimulator (ICOS), a new member of the CD28 family involved in regulation of T-cell activation and chronic intestinal inflammation, we assessed its expression and functional role in patients with inflammatory bowel disease (IBD). METHODS: Expression of ICOS, CD28, and cytotoxic T-lymphocyte antigen (CTLA) 4 on intestinal lamina propria mononuclear cells (LPMC) from patients with ulcerative colitis (UC), Crohn's disease (CD), and normal controls was determined using flow cytometry and immunohistochemistry. Expressions of the ICOS ligand, B7h, on lamina propria B cells, macrophages, and epithelial cells (EC) in the intestinal mucosa were also determined using flow cytometry. The functional costimulatory effect of ICOS on LPMC was assessed by the proliferative response and cytokine production. RESULTS: CD4(+) LPMC expressing ICOS was significantly increased in the inflamed mucosa of IBD patients but not in inflammatory or normal controls. B7h was also significantly up-regulated on B cells, macrophages, and EC in inflamed mucosa of IBD patients. Proliferative responses of anti-CD3/ICOS costimulation were significantly higher compared with those of anti-CD3 monoclonal antibody (mAb) alone. Anti-CD3/ICOS-stimulated-LPMC from UC secreted significantly increased amounts of interleukin (IL)-5 among the 3 groups. In contrast, anti-CD3/ICOS-stimulated-LPMC from CD secreted significantly increased amounts of interferon (IFN)-gamma in the presence of IL-12. CONCLUSIONS: Highly expressed ICOS in activated CD4(+) LPMC of IBD patients contributes to the dysregulated immune responses in IBD. Because ICOS hyperexpression was limited to inflammatory sites in IBD patients, ICOS would be a feasible therapeutic target for the treatment of IBD.

Antibodies, Monoclonal↗
PubMed2006

Angiogenesis as a novel component of inflammatory bowel disease pathogenesis.

BACKGROUND & AIMS: Angiogenesis is a critical component of neoplastic and chronic inflammatory disorders, but whether angiogenesis also occurs in inflammatory bowel disease (IBD) has yet to be established. We assessed mucosal vascularization, expression of endothelial alphaVbeta3 integrin, angiogenic factors, and their bioactivity in Crohn's disease (CD) and ulcerative colitis (UC) mucosa. METHODS: Mucosal endothelium was immunostained for CD31 and factor VIII and quantified by digital morphometry. alphaVbeta3 expression was studied in vivo by confocal microscopy and in vitro by flow cytometric analysis of human intestinal microvascular endothelial cells (HIMECs). Vascular endothelial growth factor (VEGF), interleukin (IL)-8, and bFGF levels were measured in mucosal extracts and cells and angiogenic bioactivity shown by induction of HIMEC migration and the corneal and chorioallantoic membrane angiogenesis assays. RESULTS: Microvessel density was increased in IBD mucosa. Endothelial alphaVbeta3 was strongly expressed in IBD but only sporadically in normal mucosa and was up-regulated in HIMECs by VEGF, tumor necrosis factor alpha, and bFGF. IBD mucosal extracts induced a significantly higher degree of HIMEC migration than control mucosa, and this response was mostly dependent on IL-8 and less on basic fibroblast growth factor or vascular endothelial growth factor. Compared with normal mucosa, IBD mucosal extracts induced a potent angiogenic response in both the corneal and chorioallantoic membrane assays. CONCLUSIONS: These results provide morphological, phenotypic and functional evidence of potent angiogenic activity in both CD and UC mucosa, indicating that the local microvasculature undergoes an intense process of inflammation-dependent angiogenesis. Thus, angiogenesis appears to be an integral component of IBD pathogenesis, providing the practical and conceptual framework for anti-angiogenic therapies in IBD.

Biopsy, Needle↗
PubMed2002

Activity related increase of exhaled nitric oxide in Crohn's disease and ulcerative colitis: a manifestation of systemic involvement?

Nitric oxide (NO) is an important mediator of inflammation in several pathological conditions. Patients with lung diseases, like asthma, have higher levels of exhaled NO (eNO) in active disease in comparison with healthy volunteers. Aspirated colonic gas in patients with ulcerative colitis (UC) showed more than 100 times higher levels of NO in comparison with normal subjects. Crohn's disease (CD) and UC are associated with a variety of systemic manifestations, although lung diseases as an extra-intestinal expression of inflammatory bowel disease (IBD) are not well investigated. In some studies, clinical and subclinical pulmonary abnormalities are described in active IBD as well as in the stable situation. The aim of the present study is to evaluate whether eNO is increased in patients with active IBD and to investigate whether there exists a correlation between (1) the eNO levels and the disease activity, and (2) the spirometry and the disease activity in a subgroup of patients. In 31 patients with CD (mean age 36.8 +/- 12.9 years) and 24 patients with UC (mean age 38.0 +/- 14.7 years) the Crohn's Disease Activity Index (CDAI) and Colitis Activity Index (CAI) were measured, respectively. Exhaled NO was measured with a chemiluminescence analyzer, according to standardized criteria. In a subgroup of CD patients, spirometry was also performed according to standardized criteria. The mean CDAI in CD patients was 192.4 +/- 94.3 and their mean eNO value was 13.5 +/- 4.6 ppb. For UC the mean CAI was 6.2 +/- 4.8 and the mean eNO value was 15.8 +/- 6.2 ppb. In a matched control group of 27 healthy, non-smoking volunteers (mean age of 33.7 +/- 13.2 years) the eNO was 10.2 +/- 2.5 ppb (P < 0.05 compared to CD and P < 0.01 compared to UC). There was a disease-activity-related increase of the eNO level in patients with IBD. For patients with UC the correlation coefficient (r = 0.63, P < 0.001) was more pronounced than for CD (r = 0.39, P < 0.05). In 17 patients with CD, spirometry was available at the time of the eNO measurement. We found a significant negative correlation between the CDAI and the FEV1 and FVC in these patients (r = -0.559, P = 0.02 and r = -0.634, P = 0.006, respectively). We conclude that eNO is increased in active IBD and correlates with the activity of the disease; furthermore, we found a negative correlation between spirometry and disease activity in patients with CD. These observations strengthen the arguments that IBD is a systemic disease. Further research is needed to try to explain the significance of an increased eNO in IBD.

Acute Disease↗
PubMed2002

Asymptomatic elevation of serum lipase and amylase in conjunction with Crohn's disease and ulcerative colitis.

BACKGROUND AND OBJECTIVE: Elevated serum lipase and amylase are often observed in IBD patients (Crohn's disease and ulcerative colitis) without clinical symptoms of a pancreatitis. The intention of this prospective study is to evaluate the frequency of elevated serum lipase and amylase with these patients and to try to explain this phenomenon in consideration of the existing literature. PATIENTS AND METHODS: 136 IBD patients (MC: 66; CU: 70) participated in this prospective study which lasted 3 months. All patients with increased levels of serum lipase and amylase were prospectively followed-up for another 3 months. RESULTS: We found an asymptomatic elevation of serum lipase and amylase without symptoms of a pancreatitis in 14 % of the observed IBD patients. A significance between the elevation of lipase/amylase and the activity index (CDAI,CAI) or the CRP level could not be found. A significant increase of lipase/amylase (more than twice the normal standard) was shown more often in lipase (4.4 %) than in amylase levels (0.7 %). The possible reasons for an asymptomatic increase of lipase/amylase in IBD patients (e. g. latent extra-intestinal involvement of the pancreas in IBD with pancreatitis; extra-pancreatic release of lipase/amylase from the inflammatory bowel; intestinal reabsorption of released lipase/amylase in the inflammatory bowel) are discussed in this text. CONCLUSION: An asymptomatic elevation of lipase/amylase in IBD patients is not infrequent (14 %). The increase of lipase or amylase, without typical symptoms, makes a pancreatitis with a required therapy unlikely. A specific pancreatitis therapy is not necessary in these cases. The therapy should be guided by the requirements of the IBD therapy.

Adolescent↗
PubMed2000

Neutropenia, neutrophil dysfunction, and inflammatory bowel disease in glycogen storage disease type Ib: results of the European Study on Glycogen Storage Disease type I.

OBJECTIVE: To investigate the incidence, the severity, and the course of neutropenia, neutrophil dysfunction, and inflammatory bowel disease (IBD) in glycogen storage disease (GSD) type Ib. METHOD: As part of a collaborative European Study on GSD type I, a retrospective registry was established in 12 European countries that included all patients with GSD-I who were known at the centers and were born from 1960 to 1995. Of a total of 288 patients with GSD-I, 57 who had GSD-Ib form the basis of this study. RESULTS: Neutropenia (defined as an absolute neutrophil count <1 x 10(9)/L) was found in 54 patients. In 64% of the patients neutropenia was documented before the age of 1 year, but in 18% of the patients neutropenia was first noted between the ages of 6 and 9 years. Neutropenia was persistent in 5 patients and intermittent without any clear cyclical course in 45. Neutrophil function was investigated in 18 patients with neutropenia and was abnormal in all. Perioral infections were reported in 37 patients, perianal infections in 27 patients, and protracted diarrhea in 23 patients. Findings on colonoscopy and radiologic studies in 10 of 20 patients suspected to have IBD were abnormal in all. All patients with IBD, perioral infections, and perianal infections had neutropenia. CONCLUSIONS: Intermittent severe neutropenia is frequently found in patients with GSD-Ib. The study also indicates that IBD in GSD-Ib is underdiagnosed; up to 77% of the patients studied had evidence of IBD, all of whom had neutropenia. IBD was not detected in those with normal neutrophil counts. These findings support the notion that neutropenia and/or neutrophil dysfunction in GSD-Ib and IBD are causally related.

Adolescent↗
PubMed2001

Dipeptidyl peptidase IV (DP IV, CD26) in patients with inflammatory bowel disease.

BACKGROUND: Dipeptidyl peptidase IV (DP IV, CD26), a serine protease with broad tissue distribution and known activity in serum, participates in T cell activation and promotes a Th1 cytokine response, a function in part attributable to its enzymatic activity. We hypothesized that the activity of DP IV in serum and expression of CD26/DP IV in lymphocytes may be altered in patients with inflammatory bowel disease (IBD). METHODS: Serum DP IV activity and CD26 (DP IV)-positive peripheral blood lymphocytes were measured in 110 patients with IBD (Crohn disease (CD): n = 63, ulcerative colitis (UC): n = 47). Additionally, T cell activation antigens (CD25, CD95) and costimulatory molecules (CD28) were evaluated. The same analyses were carried out in healthy volunteers (HC, n = 28). Thirty-nine patients with CD and 28 patients with UC were reassessed 3-6 months after the first visit. RESULTS: In patients with IBD, the DP IV activity in serum was reduced (mean +/- s (standard deviation): 52.8 U/l +/- 16.9 (CD) and 55.7 +/- 15.1 U/l (UC) versus 71.9 +/- 18.4 (HC), P < 0.001). Furthermore, patients with IBD had higher numbers of CD26-positive cells coexpressing CD25 and a higher surface expression of CD26 (DP IV) (mean fluorescence intensity, mean 57.1 (CD) and 59.8 (UC) versus 29.9 (HC), P < 0.001). The DP IV activity in serum showed an inverse correlation with known disease activity scores as well as with the concentrations of orosomucoid in serum. CONCLUSION: The changes of DP IV in patients with IBD highlight alterations at an interface between immune function and metabolism of peptide hormones, with potential importance for the pathophysiology of IBD. Furthermore, these changes may help to refine the assessment of IBD activity.

Adult↗
PubMed2002

Familial and sporadic inflammatory bowel disease: comparison of clinical features and serological markers in a genetically homogeneous population.

BACKGROUND: The familial occurrence of inflammatory bowel disease (IBD) and the clinical features of familial and sporadic IBD in the genetically homogeneous Finnish population are evaluated. METHODS: 257 patients with Crohn disease (CD) and 436 with ulcerative colitis (UC) participated in the study. They were asked whether IBD was present (familial IBD) or absent (sporadic IBD) in their first-degree relatives. Data on the clinical course of the disease were collected from the patient records. Antibodies to Saccharomyces cerevisiae (ASCA) and anti-neutrophil cytoplasmic antibodies (ANCA) were determined from serum samples. RESULTS: Affected first-degree relatives were found in 15.6% of patients with CD and in 13.8% of patients with UC. In familial cases CD was more often located in the ileum (38% versus 21%) and less often in the ileocolon (35% versus 50%) (P< 0.05) than in sporadic cases. A greater percentage of CD patients than UC patients were smokers (47% versus 13%; P < 0.01). An elevated level of IgA and/or IgG antibodies for ASCA was found more often in CD patients than in UC patients (59% versus 14%; P < 0.01), while pANCA were found more often in UC than in CD patients (48% versus 12%; P < 0.01). The combination of pANCA-ASCA+ yielded a sensitivity, specificity and positive predictive value of 48%, 92% and 90%, respectively, for CD, and the combination of pANCA + ASCA- of 55%, 94% and 90%, respectively, for UC. CONCLUSIONS: The percentage of familial IBD cases in Finland is comparable to that reported elsewhere in Europe. No important clinical differences between patients with familial and sporadic forms of the disease were found. ASCA is associated with both familial and sporadic CD and pANCA with UC, but low sensitivity diminishes their value as a serological marker of IBD or as a differential diagnostic test between CD and UC.

Adolescent↗
PubMed2003

Inflammatory bowel disease versus irritable bowel syndrome: a hospital-based, case-control study of disease impact on quality of life.

BACKGROUND: Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are intestinal diseases perceived differently by patients and doctors: the former is considered essentially as an 'organic' disease (i.e. an illness in which the role of stress or psychological factors is at best secondary to the disease itself), whereas the latter is acknowledged as a 'functional' disorder (i.e. illness thought to be more in the 'mind' than in the body of the patient). Accordingly, the respective impact of the two diseases on patients' health-related quality of life (HRQOL) is perceived to be very different. We aimed to compare the relative impact of the disease on HRQOL, psychological profile and perceived burden of stressful life events in two groups of outpatients suffering from IBS and IBD and attending our outpatient department at an Italian university hospital. Eighty patients with IBD (26 with ulcerative colitis and 54 with Crohn disease) and 85 controls with IBS formed the patient samples of the study. METHODS: Three questionnaires were given to the patients while they were attending the outpatient department because of their previously diagnosed disease, namely the SF-36 (a generic well-validated tool for measuring HRQOL), the SCL-90 (for assessing the psychological profile of patients), and the Holmes & Rahe schedule (for the assessment of stressful life experiences). The results were then compared by means of analysis of variance (ANOVA) and Bonferroni-adjusted t test, when appropriate. RESULTS: HRQOL appeared to be similarly reduced in both disease groups (SF-36 overall mean value: 58.2 +/- 16.1 in IBS patients versus 56.4 +/- 22.3 in IBD patients: P > 0.05) in comparison with normative Italian data. Furthermore, the overall severity of psychological symptoms was not statistically different between patients suffering from IBD versus IBS, as shown by SCL-90 mean scores of 0.89 + 0.45 versus 0.83 +/- 0.48, respectively (P > 0.05). On the contrary, the severity of recent stressful life experiences was perceived to be higher by IBS than by IBD patients (mean SRE score: 110.8 = 110.2 versus 61.6 +/- 78.8; P < 0.05). CONCLUSION: Our study supports the notion that, at least in referral centres, patients with IBS show health-related quality of life, psychological distress and recent occurrence of stressful life events of severity at least comparable with age-matched IBD patients.

Adult↗
PubMed2006

Screening of tumor necrosis factor receptor-associated factor 6 as a candidate gene for inflammatory bowel disease.

OBJECTIVE: The two forms of inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC), are thought to arise because of an interplay of unfavorable genetic and exogenous factors. During a genome-wide linkage study of IBD, we observed a nominal linkage to chromosome 11p12-q13 that was further confirmed upon fine density mapping. This chromosomal region contains a functional IBD candidate gene coding for tumor necrosis factor receptor-associated factor 6 (TRAF6), a signal transducer regulating innate and adaptive immunity as well as bone homeostasis. MATERIAL AND METHODS: Using denaturing high-performance liquid chromatography (dHPLC) and DNA sequencing, all exons and exon-intron boundaries of the TRAF6 gene in probands of 95 IBD families were initially screened; this material comprised 20 CD, 39 UC and 36 mixed families. RESULTS: No nucleotide changes in the coding sequence of TRAF6 were detected, but a single-base insertion/deletion polymorphism in a polythymine stretch (containing 8 or 7 thymines, respectively) in intron 3 was identified. However, examination of an extended material of 290 unrelated CD patients, 416 UC patients and 320 healthy blood donors failed to show any association with this 7T/8T variation and IBD, nor was this polymorphism related to specific clinical features in IBD. CONCLUSIONS: Our study tends to exclude a good positional and functional candidate gene, TRAF6, as an IBD predisposing gene and lends support to the idea that the function of TRAF6 is important enough not to permit structural alterations of this mediator.

Chromatography, High Pressure Liquid↗
PubMed2006

Absence of association between the multidrug resistance (MDR1) gene and inflammatory bowel disease.

OBJECTIVE: The multidrug resistance (MDR1) gene encodes for P-glycoprotein, a drug efflux pump. Mice deficient for the MDR1a gene spontaneously develop colitis. In humans, a polymorphism in exon 26 (C3435T) is associated with reduced expression levels and function of MDR1. Currently there are controversial data on the association between MDR1 and inflammatory bowel disease (IBD). The purpose of this study was to examine the involvement of this gene in IBD in a large population of Dutch patients with IBD and family-based controls. MATERIAL AND METHODS: A total of 781 IBD cases and 315 controls were investigated. CD phenotypes were determined according to the Vienna Classification. Individuals were genotyped for six single nucleotide polymorphisms (SNPs) close to and in the MDR1 locus. This included the C3435T variant and six microsatellite markers close to and in the MDR1 locus. Single locus association analysis, haplotype association analysis and haplotype sharing statistic (HSS) were used to search for differences between patients and controls. RESULTS: No association was observed for any of the SNPs with IBD as a group, or for ulcerative colitis, Crohn's disease and Crohn's disease phenotypes, either by single locus or haplotype association analysis or by HSS. CONCLUSIONS: No association was observed between the MDR1 gene and IBD. This suggests that it is unlikely that MDR1 plays a role in IBD susceptibility.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Arg506Gln factor V mutation and Val34Leu factor XIII polymorphism in Finnish patients with inflammatory bowel disease.

BACKGROUND: Earlier studies have indicated that inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is associated with thromboembolic complications, whereas inherited disorders of coagulation occur less often than expected in IBD patients. The point mutation Arg506Gln of factor V (Factor V Leiden), resulting in resistance to activated protein C, is the commonest inherited form of thrombophilia. Alterations in circulating levels of factor XIII (FXIII) have been reported among IBD patients. We investigated whether Factor V Leiden or inherited Val34Leu polymorphism of FXIII would associate with IBD or its clinical outcome. METHODS: Factor V Leiden mutation and FXIII Val34Leu polymorphism were assayed in 328 unrelated Finnish patients with UC and 235 patients with CD by solid-phase minisequencing techniques. The control groups comprised 142 apparently healthy Finnish subjects and 120 Finnish blood donors. RESULTS: The frequency of Factor V Leiden mutation among IBD patients (4.5%) was not significantly different from that in subjects living in the same area (2.1%). No significant differences could be observed in the FXIII Val34Leu polymorphism allele frequencies between patients and controls. Clinical features of IBD, including the disease extent, requirement for immunosuppressive drugs, and occurrence of complications, seemed to be independent of these two clotting factor variants analyzed. CONCLUSIONS: Our data do not support an aetiologic or disease-modifying role for the factor V mutation or factor XIII Val34Leu polymorphism in IBD.

Adult↗
PubMed2004

Perinatal outcomes in inflammatory bowel disease.

OBJECTIVE: To determine whether inflammatory bowel disease (IBD) is associated with increased risk for adverse perinatal outcome. METHODS: A case-control study of 116 singleton pregnancies with IBD compared to 56,398 singleton controls delivered between 1986 and 2001. RESULTS: Patients with IBD were slightly older (32.8 vs. 30.6 years, p < 0.001), more likely to be Caucasian or Asian than Black or Latino (92% vs. 57%, p < 0.001) and have private health insurance (33% vs. 3%, p < 0.001). IBD was associated with an increased risk for labor induction (32% vs. 24%, p = 0.002), chorioamnionitis (7% vs. 3%, p = 0.04) and Cesarean section (32% vs. 22%, p = 0.007), but there were no differences in neonatal outcomes. Subgroup analysis demonstrated an increased risk for low birth weight (LBW) in the ulcerative colitis group vs. the Crohn's disease group (19% vs. 0%, p = 0.002). Patients with prior surgery for IBD had a lower incidence of LBW (0% vs. 12%, p = 0.03). Flares during pregnancy were associated with an increased risk for preterm delivery (27% vs. 8%, p = 0.02) and LBW (32% vs. 3%, p = 0.003). CONCLUSION: IBD was an independent risk factor for Cesarean section but there was no increase in adverse perinatal outcome. Crohn's disease, prior IBD surgery and quiescent disease were associated with a lower risk for LBW.

Adult↗
PubMed2000

Effects of stratification in the analysis of affected-sib-pair data: benefits and costs.

The benefits and costs of stratification of affected-sib-pair (ASP) data were examined in three situations: (1) when there is no difference in identity-by-descent (IBD) allele sharing between stratified and unstratified ASP data sets; (2) when there is an increase in IBD allele sharing in one of the stratified groups; and (3) when the data are stratified on the basis of IBD allele-sharing status at one locus, and the stratified ASPs are then analyzed for linkage at a second locus. When there is no difference in IBD sharing between strata, a penalty is always paid for stratifying the data. The loss of power to detect linkage in the stratified ASP data sets is the result of multiple testing and the smaller sample size within individual strata. In the case in which etiologic heterogeneity (i.e., severity of phenotype, age at onset) represents genetic heterogeneity, the power to detect linkage can be increased by stratifying the ASP data. This benefit is obtained when there is sufficient IBD allele sharing and sample sizes. Once linkage has been established for a given locus, data can be stratified on the basis of IBD status at this locus and can be tested for linkage at a second locus. When the relative risk is in the vicinity of 1, the power to detect linkage at the second locus is always greater for the unstratified ASP data set. Even for values of the relative risk that diverge sufficiently from 1, with adequate sample sizes and IBD allele sharing, the benefits of stratifying ASP data are minimal.

Age of Onset↗
PubMed1999

Elevated serum thrombopoietin and interleukin-6 concentrations in thrombocytosis associated with inflammatory bowel disease.

Reactive thrombocytosis is a typical feature in inflammatory bowel disease (IBD). The question arose as to whether the normal negative feedback regulation of the concentration of thrombopoietin (TPO) in blood was altered in IBD patients. We measured serum immunoreactive TPO in 30 patients with active IBD, 29 patients with inactive IBD, and 56 healthy controls. The results were related to platelet and leukocyte counts and to the serum concentration of interleukin 6 (IL-6). Patients with active IBD exhibited significantly increased TPO levels (medians 112 pg/ml vs. 90 pg/ml in controls, p < 0.05) in association with thrombocytosis (428 platelets/nl blood vs. 241 platelets/nl blood in controls), leukocytosis, and increased IL-6 levels (12.9 pg/ml vs. 2.5 pg/nl in controls). In patients with inactive IBD, only platelets (322/nl) and leukocytes were above normal. Although the observation of increased TPO and IL-6 levels provides an explanation for the occurrence of thrombocytosis in IBD, the pathogenetic mechanisms underlying the elevated TPO level still need to be identified.

Adolescent↗
PubMed2003

Effect of malnutrition and short-term refeeding on peripheral blood mononuclear cell mitochondrial complex I activity in humans.

BACKGROUND: Previous investigations in rats have shown that the first enzyme of the mitochondrial electron transport chain (complex I) is altered in peripheral blood mononuclear cells (PBMCs) and muscle by dietary manipulations. OBJECTIVE: We hypothesized that similar changes would occur in human PBMCs as a result of dietary malnutrition and short-term refeeding irrespective of the presence or absence of active inflammatory bowel disease (IBD). DESIGN: Fourteen malnourished patients with active IBD, 13 malnourished patients without IBD, and 42 healthy subjects were investigated. Complex I activity, body mass index, body composition, energy and protein intakes, and resting energy expenditure were measured. Five patients without IBD and 6 patients with IBD were investigated after 7 d of refeeding. RESULTS: In patients without IBD, weight loss was mainly due to a loss of fat mass. In contrast, weight loss in IBD patients was due to a loss of both fat-free mass and fat mass. Complex I activity was reduced to the same degree in both groups of patients and was significantly lower than that observed in healthy subjects. In both groups of patients, complex I activity correlated significantly with body weight, body mass index, percentage weight loss, and fat mass. Complex I activity increased significantly after 1 wk of refeeding in both groups of patients before observed changes of measured nutritional assessment indexes. CONCLUSION: Our study showed that mitochondrial complex I activity measured in PBMCs seems to be a specific marker of dietary malnutrition and responds rapidly to refeeding.

Adult↗
PubMed2001

Quality of life in inflammatory bowel disease: a cross-cultural comparison of English and Canadian children.

BACKGROUND: Any disease and its treatment has an important impact on health-related quality of life for affected individuals. There have been few previous studies on the quality of life for children with inflammatory bowel disease (IBD). METHODS: A cross-cultural comparison was performed to determine whether the concerns of children with IBD in the United Kingdom are ranked similarly to those of children with IBD in Canada. An item reduction questionnaire, developed from interviews with Canadian children with IBD, was scored by 53 British children with IBD for importance and frequency, as a questionnaire had been scored previously by 117 Canadian children. RESULTS: There was a significant correlation between the mean scores (r = 0.831, P < 0.001) and ranks (r = 0.801, P < 0.001) for the 96 questions, and 43 of the 50 highest-ranking concerns corresponded for both populations. Confidence interval analysis showed a significant difference between the mean values for 21 of the 96 items; 20 of these 21 were ranked higher in the United Kingdom than they had been in Canada, suggesting that the frequency and/or degree of concern was greater for the British children with IBD. CONCLUSIONS: Health-related concerns of British children with Crohn disease and ulcerative colitis correlate closely with those of Canadian children with those diseases. Further studies are needed to determine the sensitivity of individual questions, the most appropriate wording of these questions, and the optimal length for a proposed instrument to assess quality of life in children with IBD.

Adolescent↗