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PubMed1999

Complementary and alternative medicine use by patients with inflammatory bowel disease: An Internet survey.

OBJECTIVES: To determine the degree and determinants of the use of complementary and alternative medicine (CAM) by patients with inflammatory bowel disease (IBD) with the use of the Internet and to compare the results with those found by using a similar survey in patients attending gastroenterology clinics in Calgary, Alberta. SUBJECTS AND METHODS: A cross-sectional survey of 263 patients with IBD with the use of a World Wide Web-based, structured questionnaire was conducted. RESULTS: Complementary therapies had been used by 46% of patients in the previous two years. Current use was reported by 34%. Vitamins, herbal products and natural health practices were the most commonly reported therapies. Side effects and lack of effectiveness of standard therapies were the most commonly cited reasons for seeking complementary medicine. However, despite this, respondents who had previously received surgery, or intravenous or oral steroids were less likely to be current CAM users. Important differences between the determinants of and reasons for CAM use in the present study and those of a similar study of IBD patients in a local tertiary care setting were noted. CONCLUSIONS: Complementary medicine use is common in patients with IBD. Differences in the determinants of and reasons for CAM use noted between the present Internet sample and a gastroenterology clinic sample suggest that conclusions from the present study and from previous studies based only on clinic samples provide a limited view of CAM use by people with IBD. More comprehensive assessments are needed.

Adult↗
PubMed1999

Influence of sex and disease on illness-related concerns in inflammatory bowel disease.

UNLABELLED: Identifying the normal concerns of people with ulcerative colitis and Crohn's disease (CD) facilitates a comprehensive approach to their medical care. Clinically, it can be easily appreciated that the concerns of men and women with inflammatory bowel disease (IBD) may differ and that this may have a substantial impact on both coping and treatment decisions. However, sex differences have received little empirical study. METHODS: Significant differences between the sexes on the 25 items of the Rating Form of IBD Patient Concerns (RFIPC) were determined in 343 subjects by univariate ANOVA with disease type and sex as factors, correcting for multiple comparisons and covarying for IBD symptom severity. RESULTS: Compared with men, women reported higher levels of IBD symptom severity and higher overall RFIPC scores. Women were more concerned than men about feelings related to their bodies, attractiveness, feeling alone and having children. There was an interaction between disease and sex regarding concern about sexual performance and intimacy. In both cases, men with CD reported less concern than each other comparison group. The illness concerns that differ between sexes are not the most intense concerns in either sex. DISCUSSION: These results confirm that sex has a significant influence on a number of illness concerns, particularly concerns related to self-image and relationships. The interaction of disease type and sex with respect to concern over sexual performance and intimacy is open to several potential explanations and requires further research. Sex differences should be considered in the treatment of IBD. Specific inquiry into sex-specific concerns may be useful for the clinician. Further research is required to replicate these retrospective findings.

Analysis of Variance↗
PubMed2002

Lower gastrointestinal bleeding and ischemic colitis.

OBJECTIVE: To compare the incidence and clinical characteristics of lower gastrointestinal (LGI) bleeding due to ischemic colitis with those with LGI bleeding of other causes. METHODS: A chart review was performed of patients admitted with LGI bleeding to Sunnybrook and Women's College Health Sciences Centre, Toronto, Ontario, between July 1, 1997 and January 31, 2000. RESULTS: Of 124 patients with LGI bleeding, 24 cases were due to ischemic colitis, 62 to diverticulosis, 11 to inflammatory bowel disease (IBD) and 27 to all other causes ('others'). The average ages of patients in each group were 66.5, 76.5, 40.5 and 77.5 years, respectively. Patients with ischemic colitis were statistically younger than those with diverticular bleeding and 'others'. Patients with IBD were younger than those in the other three groups. The only statistical difference for vascular disease risks was hypertension, because of its absence from the IBD group. Three patients with ischemic colitis underwent blood transfusions, while 23 with diverticulosis, 15 'others' and none with IBD received blood. Three patients with ischemic colitis and one patient from the 'others' group died. More women (75) than men (49) had LGI bleeding - in total and within each subgroup. Of women with LGI bleeding, many more with ischemic colitis (44.4%) than with diverticulosis (3.0%), IBD (0%) or 'others' (5.6%) were taking estrogen. CONCLUSIONS: Ischemic colitis was the second most common cause of LGI bleeding. LGI bleeding from all causes was more common in women than in men. Many more women in the ischemic colitis group than in the other groups were using estrogen therapy.

Adult↗
PubMed2003

6-mercaptopurine and inflammatory bowel disease: hidden ground for the cytomegalovirus.

6-mercaptopurine (6-MP) and azathioprine are important drugs for the treatment of inflammatory bowel disease (IBD) but their actions suppress host defense against infection. A challenging case of a 19-year-old female patient with quiescent Crohn's disease maintained with 6-MP presenting with dyspnea and a normal chest exam and x-ray is presented. She became ventilator-dependent and only after numerous investigations was diagnosed with cytomegalovirus (CMV) pneumonitis. A systematic literature review of CMV infections in IBD patients was performed. The present case is the first report of a patient with quiescent IBD maintained on 6-MP who developed CMV pneumonitis. Other reports have identified patients with active disease on multiple immunosuppressants who developed CMV pneumonitis and also highlight the risk of CMV colitis in refractory IBD. The authors review the approach to the diagnosis of CMV infections in IBD patients with atypical pneumonia and colitis and highlight the importance of considering CMV infection in these settings.

Adult↗
PubMed2005

[Extraintestinal manifestations in inflammatory bowel disease: differences between Crohn's disease and ulcerative colitis].

BACKGROUND AND OBJECTIVE: The true prevalence of the extraintestinal manifestations (EM) associated with inflammatory bowel disease (IBD) may vary depending on the geographic area, IBD population, location and duration of the disease, medication and diagnostic accuracy. The aim of this study was determine the prevalence of the major EM of IBD and their differences between Crohn's disease (CD) and ulcerative colitis (UC). PATIENTS AND METHOD: A prospective study with a total of 566 patients (295 CD with median follow up 11.6 years [range: 2-32 years] and 271 UC with median follow up 10.4 years [range: 2-36 years]. Data related to the clinical course, EM and laboratory tests were obtained at diagnosis and during follow-up. RESULTS: EM related with IBD appeared al least once in 46.6% of the patients. Joints manifestations were the most common EM. The EM were equal frequent in UC (51.5%) as in CD (42.2%). Hepatobiliary manifestations (odds ratio [OR] = 1.91; 95% confidence interval [CI] 1.15-3.16; p = 0.007), venous thromboembolism (OR = 4.26; 95% CI, 1.3-15.4; p = 0.006) and arthralgias (OR = 1.59; 95% CI, 1.01-2.5; p = 0.035) were more frequent in UC than CD. Erythema nodosum (OR = 2.35; 95% CI, 1.13-5.0; p = 0.013) and peripheral arthritis (OR = 1.95; 95% CI, 1.02-3.74; p = 0.029) were more frequent in CD. The prevalences of ocular, and the rest of joint manifestations were not different according to UC or CD. CONCLUSIONS: Prevalence of EM in Spanish IBD patients is among the highest ever reported. The distribution of the EM observed is different between CD and UC. It is necessary to know to allow to prompt diagnosis and prevent undesirable complications.

Adolescent↗
PubMed2006

[Diagnostic value of fecal calprotectin in predicting an abnormal colonoscopy].

BACKGROUND AND OBJECTIVE: Abdominal pain and diarrhoea are common symptoms in the general population. The colonoscopy is the gold standard method of detecting an organic pathology in the colon. However, it is invasive; it can not be repeated frecuently; it is expensive; and the system is overloaded. Fecal calprotectin (FCP) is a marker that may detect organic pathologies of the colon. The aims of this study were to analyze the usefulness of FCP to predict an abnormal colonoscopy and to correlate the levels of FCP with the degree of activity in inflammatory bowel disease (IBD). PATIENTS AND METHOD: 190 people were included in the study. All of them underwent a colonoscopy and a stool sample. People were divided in: normal colonoscopy: 117 people, and 28 colon adenomas, 20 colorectal cancer (CRC) and 25 IBD. RESULTS: The mean (SD) FCP concentration was 2,171.1 (2,133.6) mg/kgin patients with IBD and 726.6 mg/kg (533) in CRC. Both results were significantly elevated compared with those of healthy controls [114 (113)] mg/kg In patients with IBD, their levels correlated directly with the activity of the inflammation. 217 mg/kg was the best cut-off for discriminating patients with organic colon disorders. The sensibility was 85% and NPV was 93%. NSAIDs use was a clinical variable which was connected with a high FCP concentration in patients with normal colonoscopy. CONCLUSIONS: The higher levels of FCP were found in people with IBD and CRC. The measurement of FCP is a non-invasive, inexpensive, reliable and easily measured test. Among people with abdominal pain and diarrhoea, testing for FCP allows us to select those who must undergo a colonoscopy. NSAIDs can raise the levels of FCP in people with normal colonoscopies.

Adult↗
PubMedDate not supplied

Genetic epidemiology in inflammatory bowel disease.

Family studies of different designs have been carried out in the last few years. Five to ten percent of patients have another case of inflammatory bowel disease (IBD) among their first-degree relatives, with about 75-80% concordance for the same disease within the family. About 20% of multi-affected families present both cases with ulcerative colitis and Crohn's disease. The population relative risk in first-degree relatives of patients show a 14-15 times higher prevalence of IBD. Prevalence values of 1.5-3.5% in first-degree relatives have been found, with an even higher calculated lifetime risk especially in offspring and siblings of patients with IBD. Earlier disease onset in offspring of patients with IBD have consistently been found, and genetic anticipation has been hypothesized. The phenomenon, however, may be a result of a combination of a time trend - increasing the incidence of Crohn's disease - and the fact that patients with early onset of IBD may have lower fertility and therefore may be underrepresented in the parent-child pairs studied. Twin studies have shown significantly higher concordance rates in monozygotic than in dizygotic twins. Further, the concordance rate in monozygotic twins is higher in Crohn's disease than in ulcerative colitis, indicating a stronger genetic influence in this condition. Disease course and prognosis within families have been studied without convincing concordance found in this respect among family members.

Family↗
PubMedDate not supplied

Genome-wide scanning in inflammatory bowel diseases.

Inflammatory bowel diseases (IBD) are multifactorial traits involving both environmental and genetic factors. In order to identify the IBD susceptibility genes, two groups of strategies have been developed. In the candidate gene approach, a specific hypothesis is tested by usually investigating the prevalence of specific alleles in groups of affected and control individuals with no familial relationship. Such association studies are powerful and straightforward. However, they are limited by possible recruitment biases and a multitesting problem due to the large number of possible candidate genes. Furthermore, they rely on the existence of a founder effect. In the genome scanning searches, no prior assumption is made on the susceptibility genes. The studies are based on cosegregation (or linkage) analyses performed on families with several affected members. Their drawbacks are the lack of statistical power and the low resolution of the localization. Nonetheless, using genome-wide screens, two IBD loci have been localized by several independent groups on chromosomes 12 and 16. Additional IBD loci have been proposed by individual groups on chromosomes 1, 3, 4, 7, 11, 15 and X. In order to gain wide acceptance, the latter localizations are to be confirmed by additional independent studies. Identification of IBD susceptibility genes would represent a key step in the understanding of the pathogenic mechanism of these diseases. However, in complex disorders, genes are only a part of the risk factors. Epidemiological studies looking for environmental factors are thus complementary of the genetic approach.

Chromosomes, Human, Pair 12↗
PubMed2000

Role of thrombotic vascular risk factors in inflammatory bowel disease.

Thromboembolic disease is a significant cause of morbidity and mortality in patients with inflammatory bowel disease (IBD). It is recognized that a hypercoagulable state exists in IBD which involves all components of the clotting system. It has been suggested that this hypercoagulable state is closely linked to the disease pathogenesis. Recent studies have shown that genetic defects such as factor V Leiden mutation and C677T methylenetetrahydrofolate reductase polymorphism associated with hyperhomocysteinemia seem to interfere in the thrombotic manifestations of IBD. Acquired factors such as antiphospholipid antibodies could also participate in the development of the thrombotic process. Deficiencies of other anticoagulant factors play a less important role in the thrombosis, and therefore it is not surprising that the results on these factors in IBD are contradictory. In conclusion the resultant gene-gene and gene-environment interactions between risk factors are the key to the understanding of why an IBD patient develops thrombosis at a specific point in time.

Antibodies, Antiphospholipid↗
PubMed2001

Multipoint estimation of identity-by-descent probabilities at arbitrary positions among marker loci on general pedigrees.

OBJECTIVES: To describe, implement, and test an efficient algorithm to obtain multipoint identity-by-descent (IBD) probabilities at arbitrary positions among marker loci for general pedigrees. Unlike existing programs, our algorithm can analyze data sets with large numbers of people and markers. The algorithm has been implemented in the SimWalk2 computer package. METHODS: Using a rigorous testing regimen containing five pedigrees of various sizes with realistic marker data, we compared several widely used IBD computation programs: Allegro, Aspex, GeneHunter, MapMaker/Sibs, Mendel, Sage, SimWalk2, and Solar. RESULTS: The testing revealed a few discrepancies, particularly on consanguineous pedigrees, but overall excellent results in the deterministic multipoint packages. SimWalk2 was also found to be in good agreement with the deterministic multipoint programs, usually matching to two decimal places the kinship coefficient that ranges from 0 to 1. However, the packages based on single-point IBD estimation, while consistent with each other, often showed poor results, disagreeing with the multipoint kinship results by as much as 0.5. CONCLUSIONS: Our testing has clearly shown that multipoint IBD estimation is much better than single-point estimation. In addition, our testing has validated our algorithm for estimating IBD probabilities at arbitrary positions on general pedigrees.

Algorithms↗
PubMed2000

Cross-reactivity of TNP immune effector T cells that mediate contact hypersensitivity and inflammatory bowel disease in the mouse.

BACKGROUND: Experiments were aimed to test the cross-reactivity of immune Th1 cells that mediate contact hypersensitivity (CHS) or inflammatory bowel disease (IBD) to TNP in the mouse. METHODS: CBA/J mice were immunized either epicutaneously or intrarectally with TNP and after appropriate time intervals were challenged with antigen in a crossed manner. The CHS reaction was measured by the ear swelling test. IBD was quantified by increase of colon weight and myeloperoxidase level. Both reactions were confirmed histologically. In passive-transfer experiments, mesenteric lymph node cells of animals sensitized intrarectally and peripheral lymph node and spleen cells of mice immunized epicutaneously were used. In some experiments, before being immunized mice were made either unresponsive to the TNP hapten by induction of suppressor T cells, or resistant to suppression after induction of upregulatory T cells. RESULTS: Irrespective of the mode of sensitization upon appropriate challenge with antigen all mice developed a good CHS reaction as well as significant IBD. This cross-reactivity could be passively transferred by immune cells. In mice in which antigen-specific down- or upregulatory cells were induced before sensitization both CHS and IBD to TNP were modulated accordingly. CONCLUSION: TNP hapten deposited on skin or on mucosal surfaces induces effector cells that recognize antigen independent of its tissue localization, and produce a local inflammatory reaction. TNP-specific up- and downregulatory cells, shown before to regulate the CHS reaction, similarly modulate the generation and development of hapten-induced IBD.

Animals↗
PubMed2002

Construction of a confidence set of markers for the location of a disease gene using affected sib pair data.

We have previously proposed a confidence set approach for finding tightly linked genomic regions under the setting of parametric linkage analysis. In this article, we extend the confidence set approach to nonparametric linkage analysis of affected sib pair (ASP) data based on their identity-by-descent (IBD) information. Two well-known statistics in nonparametric linkage analysis, the Two-IBD test (proportion of ASPs sharing two alleles IBD), and the Mean test (average number of alleles shared IBD in the ASPs), are used for constructing confidence sets. Some numerical analyses as well as a simulation study were carried out to demonstrate the utility of the methods. Our results show that the fundamental advantages of the confidence set approach in parametric linkage analysis are retained when the method is generalized to nonparametric analysis. Our study on the accuracy of confidence sets, in terms of choice of tests, underlying disease incidence data, and amount of data available, leads us to conclude, among other things, that the Mean test outperforms the Two-IBD test in most situations, with the reverse being true only for traits with small additive variance. Although we describe how to construct confidence sets based on only two familiar tests, one can construct confidence sets similarly using other allele sharing statistics.

Confidence Intervals↗
PubMed2006

Analysis of risk factors for low bone mineral density in inflammatory bowel disease.

BACKGROUND/AIM: Several risk factors have been suggested for osteoporosis which frequently occurs in inflammatory bowel disease (IBD) patients. We studied prevalence and risk factors for reduced bone mineral density (BMD) in IBD patients at the University Hospital of Zurich, Switzerland. METHODS: The BMD was determined by dual-energy X-ray absorptiometry at the lumbar spine and femoral neck in 88 IBD patients (55 with Crohn's disease, 30 with ulcerative colitis, and 3 with indeterminate colitis). Z scores were obtained by comparison with age- and sex-matched normal values, and T scores by comparison with sex-matched healthy young adults. Osteopenia and osteoporosis were defined according to the WHO guidelines. Predictive factors for BMD were analyzed by group comparison and stepwise regression analysis. RESULTS: Osteopenia was present in 43% of the patients at the lumbar spine and in 42% of them at the femoral neck. Osteoporosis was present in 14% of the patients at the lumbar spine and in 5% of them at the femoral neck. At the lumbar spine, stepwise regression analysis showed that body mass index, age, number of bowel resections, topic steroids, and azathioprine correlated with the Z scores. Cumulative steroid dose, topic steroids, age and bowel resection were found to be predictors for a pathological T score. At the femoral neck, regression analysis showed that body mass index, age, topic steroids, and azathioprine correlated with the Z scores. Only a low body mass index was a significant predictor for pathological femoral T scores. CONCLUSIONS: Osteopenia and osteoporosis are commonly found in IBD patients. Steroid treatment and bowel resection were significant risk factors for osteoporosis of the lumbar spine. However, disease-inherent factors also appear to confer a major risk, indicating that the BMD should be determined in all IBD patients, irrespective of steroid treatment.

Absorptiometry, Photon↗
PubMed2006

A pilot study on chemospecific duodenal visceral sensitivity in inflammatory bowel disease in remission.

BACKGROUND: Patients with inflammatory bowel disease (IBD) in remission frequently experience symptoms resembling irritable bowel syndrome (IBS). In IBS altered motility and visceral sensitivity are found throughout the whole gastrointestinal tract. We aimed to study chemospecific antroduodenal sensitivity in IBD patients. METHODS: Antroduodenal manometry was performed in 10 IBD patients in remission and 13 controls. Small volumes of nutrients and acid were administered intraduodenally. Motility variables and sensation scores were compared before and after each infusion. RESULTS: Acid and lipid infusion decreased the number of antral pressure waves in both groups (p < 0.05). After acid infusion the number of duodenal pressure waves in the sideholes just distal to the infusion port increased in IBD patients compared to the controls (p < 0.05). Lipid infusion increased the number of duodenal propagated pressure waves in both groups, but in controls they were also increased over longer distances (p < 0.005). None of the infusions significantly affected the sensation scores. CONCLUSION: Subtle alterations in chemospecific responses to lipids and acid in IBD patients in remission were observed, affecting duodenal motor activity but not duodenal perception. These changes are indicative of changes at the chemoreceptor level in the duodenal wall in this patient group.

Analysis of Variance↗
PubMedDate not supplied

Mucosal substance P receptor expression in HIV infection and inflammatory bowel disease.

Gastrointestinal (GI) disease is a common manifestation of HIV infection. Symptoms may result from the acquisition of intestinal infection, but in certain cases functional and mucosal abnormality may result from mucosal HIV infection. The pathogenesis of HIV enteropathy is poorly understood, but a range of neuroenteric disturbances has been described including a reduction in mucosal substance P (SP). Inflammatory bowel disease (IBD) is a generic term used to describe two major clinical entities; Crohn's disease (CD) and ulcerative colitis (UC). Dysregulation of mucosal neuropeptide expression has been implicated in the pathogenesis of CD and UC. Mucosal SP expression has been variously described as increased, normal or reduced in intestinal tissue from patients with IBD. In contrast, uniform increases in mucosal SP receptor (SPR) have been described in patients with IBD using quantitative autoradiography. The purpose of this study was to characterize intestinal mucosal SPR mRNA expression in control, HIV and IBD patients using semiquantitative reverse transcription PCR. Intestinal tissue was obtained during diagnostic colonoscopy from 7 control, 9 HIV-infected and 28 (12 CD and 16 UC) IBD patients. RNA was isolated from the tissue biopsies, reverse transcribed and amplified with primers specific for SPR. SPR mRNA expression was detected in 7/7 (100%) of control, 2/9 (22%) of HIV-infected, 12/12 (100%) of CD and 11/16 (69%) of UC intestinal biopsies. These data demonstrate that SPR mRNA expression is significantly reduced in patients with HIV infection. Reduced mucosal SPR expression may contribute to the mucosal abnormality, altered intestinal motility and GI symptoms associated with HIV infection.

Adult↗
PubMed1994

Colonic mucosal interleukin 1 receptor antagonist in inflammatory bowel disease.

To clarify the role of the interleukin 1 receptor antagonist (IL-1ra) in patients with inflammatory bowel disease (IBD), we assessed the local IL-1ra concentrations in tissue homogenates using a specific enzyme-linked immunosorbent assay and examined the immunohistochemical localization using a monoclonal antibody against IL-1ra. In patients with IBD, regardless of the disease activity, the mucosal concentration of IL-1ra in affected areas was elevated, and the concentration during the active phase was comparable to that measured during the inactive phase. In contrast, the IL-1 beta tissue concentration was higher during the active than during the inactive phase. The IL-1ra/IL-1 beta tissue concentration ratio in the affected areas was decreased in patients with active IBD as compared with normal controls or patients with other types of colitis. Immunohistochemical studies identified lamina propria mononuclear cells, especially macrophages, as the major source of IL-1ra in IBD tissue. Our results suggest that IL-1ra plays a pivotal role in regulating inflammation in IBD.

Adolescent↗
PubMed1998

Small airways function in patients with inflammatory bowel disease.

It has been reported that in patients with inflammatory bowel disease (IBD), the airways are involved, and a number of clinical manifestations have been described. The aim of this study was to investigate the function of the small airways in IBD. Thirty patients with IBD (mean age, 47 yr), 12 with Crohn's disease and 18 with ulcerative colitis, were studied and compared with a control group of 16 normal subjects. Maximal expiratory flow-volume curves were performed breathing room air and a mixture of 80% helium, 20% oxygen. The differences of flows at 50% of FVC (delta Vmax50) and the volume of equal flows (Visov) were calculated as indices of small airways function. In addition, spirometry, lung volumes, and diffusing capacity were measured. Visov was statistically significantly greater in patients with either CD or UC than in control subjects (x +/- SD) (24.99 +/- 1.35 and 25.95 +/- 1.5 versus 20.1 +/- 1.39), (p < 0.01 and p < 0.001, respectively). A reduction in TL(CO) was noticed in the active stage of the disease in both groups of patients (p < 0.05). This may indicate that lung parenchyma is also involved in active IBD. Our results suggest that the function of the small airways and diffusion capacity of the lungs are affected in patients with IBD.

Adult↗
PubMed2026

UHRF1 deficiency exacerbates intestinal inflammation by epigenetic modulation of NPY1R gene methylation.

Epigenetic modifications play a crucial role in the pathogenesis of inflammatory bowel disease (IBD) by mediating gene-environment interactions. We previously showed that UHRF1, a central regulator of DNA methylation, contributes to cancer progression; however, its function in IBD remains poorly understood. Here, we revealed that UHRF1 was frequently reduced in inflamed tissues of patients with IBD and that its deficiency exacerbated intestinal epithelial cell (IEC) damage. Through a multilevel approach incorporating human cell models and an intestinal epithelial-specific Uhrf1-KO mouse model, we established UHRF1 as a key mitigator of IBD progression. Mechanistically, UHRF1 bound to the NPY1R promoter, promoted its methylation, and led to transcriptional suppression. The NPY1R upregulation resulting from UHRF1 deficiency attenuated cAMP/PKA/CREB signaling in IECs, thereby enhancing NF-&#x3ba;B activation and subsequent proinflammatory responses, which compromised intestinal epithelial barrier integrity. Furthermore, we identified miR-141 as a negative regulator of NPY1R, highlighting its potential as a therapeutic agent. Collectively, our results identified the UHRF1/NPY1R regulatory axis as a critical epigenetic mechanism in intestinal inflammation and underscored its dual promise for IBD diagnostics and therapy.

Animals↗