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Kinds of UC Terms modified by UC Selected AbstractsTwenty-five-year course and outcome in anxiety and depression in the Upper Bavarian Longitudinal Community StudyACTA PSYCHIATRICA SCANDINAVICA, Issue 1 2010M. M. Fichter Fichter MM, Quadflieg N, Fischer UC, Kohlboeck G. Twenty-five-year course and outcome in anxiety and depression in the Upper Bavarian Longitudinal Community Study. Objective:, Assessment of 25-year course of pure and mixed anxiety and depression in a community sample. Method:, Participants were grouped into pure anxiety, pure depression, mixed anxiety and depression, and no anxiety or depressive syndrome at baseline. Assessments consisted of a: i) baseline survey, ii) 5-year follow-up, iii) 25-year follow-up. Self-rating scales as well as expert-rating interviews yielded data on social and psychopathological risk factors and outcome measures. Results:, Baseline prevalence for mixed anxiety and depressive syndrome was 8.7%. Subjects with combined anxiety and depressive syndrome were more predisposed towards later adverse mental health outcomes and reduced functionality. The transition from anxiety syndrome (pure and mixed) to depressive syndrome over the 25-year study is more likely than the reverse. Logistic regression analysis emphasized the impact of early anxiety syndromes on later depression. Conclusion:, Results underscore the long-term risks of suffering from a combined anxiety and depressive syndrome. [source] DIAGNOSIS AND CLINICAL COURSE OF ULCERATIVE GASTRODUODENAL LESION ASSOCIATED WITH ULCERATIVE COLITIS: POSSIBLE RELATIONSHIP WITH POUCHITISDIGESTIVE ENDOSCOPY, Issue 4 2010Takashi Hisabe Background and Aim:, Ulcerative colitis (UC) is not only characterized by pathological lesions localized to colonic mucosa, but also to various complications involving other organs, including postoperative pouchitis. Among these complications, diffuse gastroduodenitis with lesions resembling colonic lesions has been reported, albeit rarely. The aim of the present study was to attempt to characterize the lesions of the upper gastrointestinal tract occurring as a complication of UC, and to assess the frequency and clinical course of these lesions. Methods:, A total of 322 UC patients who had undergone upper gastrointestinal endoscopy were retrospectively analyzed. We assessed the frequency of endoscopic findings, including diffuse gastroduodenal lesions resembling colonic lesions. Ulcerative gastroduodenal lesion (UGDL) associated with UC was diagnosed if lesions satisfied the following criteria: (i) improvement of the lesions with treatment of UC; and/or (ii) resemblance to UC in pathological findings. Results:, UGDL satisfying the aforementioned criteria was found in 15 (4.7%) of 322 patients. All the 15 patients had UGDL accompanied by pancolitis or after proctocolectomy. Frequency in 146 patients with pancolitis was 6.2% (nine patients) and that in 81 patients who had undergone proctocolectomy was 7.4% (six patients). Four patients with diffuse ulcerative upper-gastrointestinal mucosal inflammation (DUMI) had pouchitis. In all patients except one, the lesions resolved easily with medical treatment. Conclusions:, In more than half of the post-proctocolectomy patients, UGDL was related to the occurrence of pouchitis. The existence of characteristic UGDL must be taken into account in the diagnosis and treatment of UC, and UGDL is possibly related to the occurrence of pouchitis. [source] REFRACTORY DIVERTICULAR COLITIS WITH PROGRESSIVE ULCERATIVE COLITIS-LIKE CHANGES EXTENDING TO THE RECTUMDIGESTIVE ENDOSCOPY, Issue 3 2009Tateki Yamane A 68-year-old man visited our department because of diarrhea and bloody stools. Colonoscopy revealed diverticula scattered in the sigmoid colon with localized mucosal edema and reddening. The mucosa became somewhat rough 9 months later, and had an erosive, ulcerative colitis (UC)-like appearance after a further 6 months, with these changes extending to the rectum. These findings led to a diagnosis of diverticular colitis (DC) with UC-like changes. The condition was refractory to treatment including drug therapy and was thus surgically treated. No cases of DC have been reported in Japan, and a refractory case of DC with progressive UC-like changes extending to the rectum is rare even in Europe and the USA. [source] MAGNIFYING COLONOSCOPY FOR THE DIAGNOSIS OF INFLAMMATORY CHANGES IN ULCERATIVE COLITISDIGESTIVE ENDOSCOPY, Issue 3 2006Satoshi Sugano Background:, Endoscopic observation is the most effective method for the evaluation of staging in ulcerative colitis (UC). However, in cases with very mild inflammatory activity, histopathological diagnosis may also be required. Unfortunately, biopsy-related accidents are not uncommon. As an alternative, we have used a magnifying colonoscope commonly used for tumor diagnosis to examine in detail the colon mucosa of UC patients in clinical remission, and then compared these findings relative to conventional endoscopy using histopathological diagnosis. Subjects and Methods:, Among UC cases examined by colonoscopy between April 2000 and April 2005, 27 cases without hematochezia for at least 1 month were enrolled in this study. Following observations of inflammatory changes using conventional colonoscopy, magnifying observation and biopsies at a total of 144 sites were evaluated. Using histopathological standards, acute-phase inflammation was indicated by the presence of neutrophil infiltration, whereas chronic-phase inflammation was indicated by infiltration of lymphocytes, plasma cells and eosinophils. Results:, Indicators of significant inflammation by conventional observation was erosion. Under magnification, inflammation appears as superficial defects in mucosa and small whitish spots. When the presence of infiltrating neutrophils was used as a positive histological marker for inflammation, there was no difference in the accuracy of diagnosis by conventional observation (95.1%) versus magnifying observation (97.2%). In contrast, when lymphocyte infiltration was used as a marker, the accuracy of diagnosis increased significantly (88.2%) using magnifying observation relative to conventional observation (61.1%). Conclusions:, Magnifying endoscopy can be used effectively in the evaluation of minute mucosal changes in cases of UC remission. [source] Evaluation of gastroduodenal mucosal lesions in patients with Crohn's disease and ulcerative colitisDIGESTIVE ENDOSCOPY, Issue 3 2004Kazuhiro Maeda Background:, Patients with Crohn's disease (CD) are reported to suffer from upper gastroduodenal lesions with varying frequency, although concurrent Helicobacter pylori infection is reported to be low. Methods:, A prospective study was carried out on patients diagnosed with CD or ulcerative colitis (UC) in order to evaluate the degree of upper gastroduodenal tract involvement and the prevalence of Helicobacter pylori infection. Results:, Gastroduodenal lesions were found in 18 (78%) of 23 CD patients, the location being the stomach in 18 (78%), the duodenal bulb in 16 (70%) and the descending duodenum in 16 (70%). Bamboo joint-like lesions were found in four cases (17%) in gastric body and cardia. In contrast, gastroduodenal lesions were found in 10 (53%) of 19 UC patients, the location being the stomach in nine (47%), the duodenal bulb in six (32%), and the descending duodenum in three (16%). The H. pylori -positive rate in patients with CD and UC was 0%, and 11%, respectively. Conclusion:, Minute upper gastroduodenal lesions are much more common in CD than in UC patients, especially in the descending duodenum. Accordingly, upper gastrointestinal endoscopy would seem to be a useful means with which to obtain a definitive diagnosis in all suspected IBD cases. [source] Three-dimensional reconstruction of the mucosa from sequential sections of biopsy specimens of patients with ulcerative colitis: Relationship between crypt structure and vascular architectureDIGESTIVE ENDOSCOPY, Issue 2 2004Hiroo Furukawa Background:, In a previous paper, the stereographic reconstruction of the crypt structure of ulcerative colitis using the RATOCK System was described. The relationship between the blood vessels and the crypt structure is the focus of the current paper, using two kinds of tissue staining color in which the color differs. Stereographic images make the relationship between the crypt structure and blood vessel distribution understandable at a glance. Methods:, The methods used here are identical to those described in a previous paper. In the present paper, five cases of ulcerative colitis (UC) are examined. Biopsy specimens were obtained from the diseased, normal, and transitional zones (the area between the normal and diseased zones) from each patient. Three-dimensional reconstruction was created using TRI for Windows (RATOC System Tokyo, Japan) software. In the present paper, two kinds of dyeing method between H&E and monoclonal antibody staining of the tissue was used. It was proven that the distribution of gland and blood vessel is very clear in the 3-D reconstruction shown. Results:, (i) The blood vessels in the normal zones run parallel to the crypt in a regular manner and are almost identical to one another in diameter. (ii) In the transitional and diseased zones, the blood vessels show no clear direction and produce many branches without any apparent order. The blood vessels are, moreover, irregular in diameter. (iii) In short, clear parallelism is lost in both the transitional and diseased zones. Conclusion:, Stereographic reconstruction of endoscopically obtained biopsy specimens of UC-affected tissues makes it possible to understand at a glance the distribution of blood vessels and their relationship to crypts. The relationship of these was clarified by the combined use of two kinds of dyeing method with three-dimensional reconstruction. [source] Nitric oxide and p53 in cancer-prone chronic inflammation and oxyradical overload disease,ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 1 2004Julie E. Goodman Abstract Nitric oxide (NO·), which is generated under chronic inflammatory conditions that predispose individuals to cancer, has paradoxical effects. NO· can activate p53, which can result in anti-carcinogenic effects, or it can be mutagenic and increase cancer risk. We explored the mechanisms by which NO· induced p53 activation in vitro and found that NO· induced p53 accumulation and phosphorylation, particularly at ser-15, via ATM and ATR kinases, which then led to cell cycle arrest at G2/M. We next examined proteins in these pathways in both inflamed and normal human colon tissue. Inducible nitric oxide synthase (iNOS) levels and p53-P-ser15 levels were positively correlated with the degree of inflammation and with each other. Additionally, the p53 targets, HDM-2 and p21 (WAF1), were present in ulcerative colitis (UC) colon, but undetectable in normal colon, consistent with activated p53. We also found higher p53 mutant frequencies of both G:C , A:T transitions at the CpG site of codon 248 and C:G , T:A transitions at codon 247 in lesional colon tissue from UC cases versus nonlesional tissue from these cases or colon tissue from normal adult controls. Consistent with nitrosative stress and the deamination of 5-methylcytosine, p53 mutations were also detected in sporadic colon cancer tissue and were associated with iNOS activity in these tissues. These studies identified a potential mechanistic link between NO· and p53 in UC and sporadic colon cancer. Environ. Mol. Mutagen. 44:3,9, 2004. Published 2004 Wiley-Liss, Inc. [source] Testing mechanisms of action for intensive case managementADDICTION, Issue 3 2008Jon Morgenstern ABSTRACT Aim This study identified factors that predict, mediate or moderate the effects of intensive case management (ICM) on longer-term drug abstinence outcomes in women on welfare. Design In a parent study women were assigned randomly to usual care (UC) or intensive case manangement (ICM). Treatment was provided for 12 weeks and follow-up continued for 15 months after study intake. A set of hypothesized mediators was assessed at month 3 and a rigorous four-step mediational model was tested using outcomes in months 4,15. Participants Participants were 302 drug-dependent women applying and eligible for federal welfare and not currently in drug abuse treatment. Interventions ICM provided intensive treatment engagement including voucher incentives for treatment attendance and case management services; UC provided primarily referral to community treatment programs. Measurement Substance use outcomes were assessed using the time-line follow-back interview and confirmed using biological and collateral measures. Findings Participants in ICM had more case manager contacts, better treatment engagement and more self-help attendance than did those in UC. Each of these variables predicted, and was shown to be a mediator of outcome, but case management contact was an especially robust mediator. Further, ICM effects were strongest for those who attended treatment least. Contrary to prediction, greater psychopathology and environmental stressors did not predict worse outcomes. Conclusions Findings suggest that case management is an active intervention that may both facilitate and substitute for formal drug abuse treatment. [source] Potential role of soluble angiopoietin-2 and Tie-2 in patients with inflammatory bowel diseaseEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2 2006I. E. Koutroubakis Abstract Background, Angiogenesis has been suggested to play an important role in inflammatory bowel disease (IBD). The aim of the study was to evaluate the serum markers of angiogenesis angiopoietin-2 (Ang-2) and soluble angiopoietin receptor Tie-2 in patients with ulcerative colitis (UC) and Crohn's disease (CD). Materials and methods, Serum Ang-2 and Tie-2 serum levels were measured in 160 IBD patients (79 UC and 81 CD) and in 80 matched healthy controls using commercially available enzyme-linked immunosorbent assays. Serum Ang-2 and Tie-2 levels were correlated with the disease activity, as well as the type, localization and treatment of the disease. Results, Median serum Ang-2 and Tie-2 levels were significantly higher in both the UC patients and the CD patients compared with the healthy controls (P < 0·05 and P < 0·001, respectively). The IBD patients with early disease (diagnosis < 2 years) had significantly higher (P = 0·04) median serum Ang-2 levels but significantly lower (P = 0·02) median serum Tie-2 levels as compared with IBD patients with late disease (diagnosis > 2 years). The CD patients with active disease had significantly higher levels of Ang-2 compared with non-active disease (P = 0·02). Serum levels of both Ang-2 and Tie-2 were not correlated with laboratory markers such as ESR, CRP, white blood cell count, platelet count and albumin. Conclusions, Serum Ang-2 and Tie-2 levels are elevated in patients with IBD. These markers may mediate angiogenesis and vascular permeability in the mucosa of patients with IBD. [source] Neurologic manifestations of ulcerative colitisEUROPEAN JOURNAL OF NEUROLOGY, Issue 5 2007R. Scheid Ulcerative colitis (UC) has traditionally been considered to be an inflammatory disease limited to the colonic mucosa. However, since it has been shown that UC is frequently accompanied by various extraintestinal disorders, there is increasing evidence that UC may also manifest in the nervous system. The following review focuses particularly on these possible manifestations of UC, both in the peripheral (PNS), and in the central nervous system (CNS). A systematic literature search according to the MEDLINE database was performed for this purpose. Although a reliable differentiation may clinically not always be possible, three major pathogenic entities can be differentiated: (i) cerebrovascular disease as a consequence of thrombosis and thromboembolism; (ii) systemic and cerebral vasculitis; (iii) probably immune mediated neuropathy and cerebral demyelination. With the exception of thromboembolism and sensorineural hearing loss, evidence for a causal relationship relies merely on single case reports or retrospective case series. Considering the CNS-manifestations, similarities between UC-associated disorders of the white matter and acute disseminated encephalomyelitis (ADEM) are obvious. Epileptic seizures, unspecified encephalopathies and confusional states are most likely epiphenomena that have to be regarded symptomatic rather than as own entities. A prospective study on the neurologic aspects of UC would be very welcome. [source] Assessing the Validity of Insurance Coverage Data in Hospital Discharge Records: California OSHPD DataHEALTH SERVICES RESEARCH, Issue 5 2003Thomas C. Buchmueller Objective. To assess the accuracy of data on "expected source of payment" in the patient discharge database compiled by the California Office of Statewide Health Planning and Development (OSHPD). Data Sources. The OSHPD discharge data for the years 1993 to 1996 linked with administrative data from the University of California (UC) health benefits program for the same years. The linked dataset contains records for all stays in California hospitals by UC employees, retirees, and spouses. Study Design. The accuracy of the OSHPD data is assessed using cross-tabulations of insurance type as coded in the two data sources. The UC administrative data is assumed to be accurate, implying that differences between the two sources represent measurement error in the OSHPD data. We cross-tabulate insurance categories and analyze the concordance of dichotomous measures of health maintenance organization (HMO) enrollment derived from the two sources. Principal Findings. There are significant coding errors in the OSHPD data on expected source of payment. A nontrivial percentage of patients with preferred provider organization (PPO) coverage are erroneously coded as being in HMOs, and vice versa. The prevalence of such errors increased after OSHPD introduced a new expected source of payment category for PPOs. Measurement problems are especially pronounced for older patients. Many patients over age 65 who are still covered by a commercial insurance plan are erroneously coded as having Medicare coverage. This, combined with the fact that during the period we analyzed, Medicare HMO enrollees and beneficiaries in the fee-for-service (FFS) program are combined in a single payment category, means that the OSHPD data provides essentially no information on insurance coverage for older patients. Conclusions. Researchers should exercise caution in using the expected source of payment in the OSHPD data. While measures of HMO coverage are reasonably accurate, it is not possible in these data to clearly identify PPOs as a distinct insurance category. For patients over age 65, it is not possible at all to distinguish among alternative insurance arrangements. [source] RET rearrangements and BRAF mutation in undifferentiated thyroid carcinomas having papillary carcinoma componentsHISTOPATHOLOGY, Issue 3 2010Kunio Mochizuki Mochizuki K, Kondo T, Nakazawa T, Iwashina M, Kawasaki T, Nakamura N, Yamane T, Murata S-i, Ito K, Kameyama K, Kobayashi M & Katoh R (2010) Histopathology,57, 444,450 RET rearrangements and BRAF mutation in undifferentiated thyroid carcinomas having papillary carcinoma components Aims:, To elucidate the genetic background of anaplastic transformation, RET rearrangements and BRAF mutation were studied in composite undifferentiated carcinomas (UCs) of the thyroid, which are UCs having papillary carcinoma (PC) components. Methods and results:, Reverse transcription,polymerase chain reaction (RT,PCR) was performed for RET rearrangements and PCR for BRAF mutation in UC and PC components that were microdissected separately from seven composite UCs. Forty-two thyroid cancers with single component histology (14 UCs and 28 PCs) were also studied in the same manner. RET/PTC1 was undetectable in both components from all seven composite UCs, and RET/PTC3 was identified in both components of one composite UC. BRAF mutation was identified in both components from three composite UCs and only in the PC components from two composite UCs. In contrast, in thyroid carcinomas with single component histology, RET/PTC1 was detected in 11% of PCs and in none of the UCs, and RET/PTC3 was not found in any of the tumours studied. BRAF mutation was identified in 82% of PCs and in 21% of UCs. Conclusions:, The high frequency of BRAF mutation and the absence of RET rearrangements in UC components from composite UCs supports the hypothesis that UCs may actually represent progressive malignant degeneration of a BRAF -mutated, well-differentiated thyroid carcinoma. [source] Diagnostic difficulties in inflammatory bowel disease pathologyHISTOPATHOLOGY, Issue 2 2006R K Yantiss This review summarizes some of the common diagnostic problems encountered by pathologists when evaluating patients with chronic colitis and in whom inflammatory bowel disease (IBD) is either suspected or within the differential diagnosis. Both ulcerative colitis (UC) and Crohn's disease (CD) show characteristic, but non-specific, pathological features that may overlap and result in a diagnosis of ,indeterminate colitis' (IC). However, other reasons why pathologists may entertain a diagnosis of IC include failure to recognize or accept certain ,hardcore' histological features as indicative of CD, an attempt to classify cases of chronic colitis based on mucosal biopsy material or in the absence of adequate clinical and radiographic information, and the presence of other disease processes that mask, or mimic, IBD. In addition, some cases of UC may show unusual CD-like features, such as discontinuous or patchy disease, ileal inflammation, extracolonic inflammation, granulomatous inflammation in response to ruptured crypts, aphthous ulcers, or transmural inflammation. Furthermore, other forms of colitis, such as microscopic colitis, diverticulitis and diversion colitis may, on occasion, also show IBD-like changes. The clinical and pathological features that aid in the distinction between these entities, and others, are covered in detail in this review. [source] Efficacy of methotrexate in ulcerative colitis: Failure or promiseINFLAMMATORY BOWEL DISEASES, Issue 8 2010Hans H. Herfarth MD Abstract Background: Low-dose methotrexate is a widely used and efficacious therapy in chronic inflammatory disorders such as psoriasis and rheumatoid arthritis. Prospective randomized controlled trials have demonstrated the efficacy of parenteral methotrexate in Crohn's disease (CD). We performed a systematic review of the efficacy of methotrexate in ulcerative colitis (UC) and discuss the results in the context of the known pharmacokinetics and adverse events of methotrexate therapy in inflammatory bowel diseases and other inflammatory conditions. Materials and Methods: We performed a systematic review of the literature in Medline, Embase, and Web of Science. All publications describing patients with UC treated with methotrexate were included. Results: We identified 12 studies or retrospective case series and 5 meeting abstracts that met the inclusion criteria. Only 1 study reported a prospective randomized placebo-controlled trial using methotrexate at a dose of 12.5 mg orally with no significant clinical benefit. However, the majority of uncontrolled retrospective analyses suggest a clinical response to methotrexate therapy in a range of 30%,80% when the drug is applied by parenteral route in doses between 20,25 mg. Conclusions: The only randomized controlled trial of methotrexate in UC employed oral dosing and doses lower than those shown to be effective in CD and did not demonstrate efficacy, whereas uncontrolled, retrospective studies using doses and routes of administration similar to those employed in CD suggest benefit. Well-designed, prospective, placebo-controlled trials of methotrexate in UC are needed. Inflamm Bowel Dis 2010 [source] Preserved Na+/H+ exchanger isoform 3 expression and localization, but decreased NHE3 function indicate regulatory sodium transport defect in ulcerative colitis,INFLAMMATORY BOWEL DISEASES, Issue 7 2010Sunil Yeruva PhD Abstract Background: A major causative factor of diarrhea in ulcerative colitis (UC) patients is the loss of Na+ absorptive capacity of the inflamed colonic mucosa. Potential contributing mechanisms include reduced driving force for active transport, and impaired expression, mislocalization, or defective transport function of Na+ absorptive proteins. We therefore studied the expression, brush border membrane (BBM) localization, and transport capacity of the major intestinal Na+ absorptive protein, the Na+/H+ exchanger isoform 3 (NHE3) in biopsies from UC patients. Methods: In UC and control biopsies, inflammation was graded histologically, NHE3, tumor necrosis factor alpha (TNF-,), villin, as well as other housekeeping genes were analyzed by quantitative real-time polymerase chain reaction (PCR), BBM localization of NHE3 determined by immunohistochemistry, and confocal microscopy. Na+ absorptive capacity was assessed by 22Na+ isotope fluxes and NHE3 transport activity measured microfluorometrically in BCECF-loaded surface colonocytes within isolated crypts. Results: In mildly, moderately, and severely inflamed sigmoid colon of UC patients, neither NHE3 mRNA expression nor the abundance of NHE3 in the BBM was significantly altered compared to other structural components of the BBM. However, Na+ absorption was strongly reduced by ,80% and acid-activated NHE3 transport activity was significantly decreased in the surface cells of sigmoid colonic crypts even in moderately inflamed mucosa. Conclusions: In the colonic mucosa of patients with active UC, NHE3 transport capacity was found significantly decreased despite correct NHE3 location and abundance in the brush border, independent of current treatment. These findings suggest functional NHE3 transport as a novel factor for inflammatory diarrhea in UC patients. (Inflamm Bowel Dis 2010) [source] Lipopolysaccharide exposure is linked to activation of the acute phase response and growth failure in pediatric Crohn's disease and murine colitis,INFLAMMATORY BOWEL DISEASES, Issue 5 2010Brad A. Pasternak MD Abstract Background: Systemic exposure to lipopolysaccharide (LPS) has been linked to clinical disease activity in adults with inflammatory bowel disease (IBD). We hypothesized that markers of LPS exposure and the acute phase response (APR) would be increased in pediatric IBD patients with growth failure, and that LPS signaling would be required for induction of the APR in murine colitis. Methods: Serum markers of LPS exposure, endotoxin core IgA antibody (EndoCAb), and the APR, LPS binding protein (LBP) were quantified in pediatric IBD patients and controls. LBP and cytokine production were determined after administration of trinitrobenzene sulfonic acid (TNBS) enemas to mice with genetic deletion of Toll-Like receptor 4 (TLR4), and wildtype (WT) controls. Results: Serum EndoCAb and LBP were significantly elevated in patients with Crohn's disease (CD), compared to disease controls with ulcerative colitis (UC) and healthy controls (P < 0.001). This was independent of disease activity or location. CD patients with elevated serum EndoCAb and LBP exhibited linear growth failure which persisted during therapy. Serum LBP increased in WT mice following TNBS administration, in conjunction with increased serum TNF-,, IL-6, and IL-10, and expansion of regulatory T-cell numbers. Both the APR and expansion of foxp3+ T cells were abrogated in TLR4-deficient mice, in conjunction with a reduction in acute weight loss. Conclusions: LPS exposure and a persistent APR are associated with growth failure in pediatric CD. LPS signaling is required for the APR in murine colitis. Therapies targeting this pathway may benefit the subset of patients with refractory growth failure. (Inflamm Bowel Dis 2010) [source] CXCL12 Is a constitutive and inflammatory chemokine in the intestinal immune systemINFLAMMATORY BOWEL DISEASES, Issue 4 2010Iris Dotan MD Abstract Background: Inflammatory bowel disease (IBD) is characterized by increased lymphocytic infiltrate to the lamina propria (LP) and upregulation of inflammatory chemokines and receptors. CXCL12 is a constitutive chemokine involved in lung, brain, and joint inflammation. We hypothesized that CXCL12 and its receptor, CXCR4, would have a constitutive and inflammatory role in the gut. Methods: Intestinal epithelial cells (IECs) and T lymphocytes were isolated from intestinal mucosa of IBD and control patients undergoing bowel resection. Autologous T cells were isolated from peripheral blood (PB). CXCL12 and CXCR4 expression by IECs was assessed by polymerase chain reaction and immunohistochemistry, lymphocyte phenotype by flow cytometry, and migration by Transwells. Results: IECs expressed CXCL12 and expression was increased and more diffuse in IBD compared to normal crypts (ulcerative colitis [UC] > Crohn's disease [CD], inflamed > noninflamed). CXCR4 was expressed by IECs, LP T cells (LPTs), and PB T cells (PBTs), and CXCR4+ cells were increased in IBD LP in situ. PBTs and LPTs from all patients had a high and comparable migration toward CXCL12 (P < 0.0001 and P < 0.05 vs. medium, respectively). Migration toward IBD-IEC-derived supernatant was significantly higher compared to normal. Antibodies against CXCR4 and CXCL12 blocked migration. Conclusions: CXCL12 is expressed by normal IECs and upregulated and differentially distributed in IBD IECs. CXCR4 is expressed by IECs and LPTs, and CXCR4+ cells are significantly increased in IBD LP. CXCL12 is chemotactic for both PBTs and LPTs. Thus, CXCL12 and CXCR4 have a constitutive and inflammatory role in the intestinal mucosa and their selective therapeutic manipulation may be considered in IBD management. (Inflamm Bowel Dis 2009;) [source] Value of fractional exhaled nitric oxide (FENO) for the diagnosis of pulmonary involvement due to inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 4 2010Ezgi Ozyilmaz MD Abstract Background: Pulmonary involvement due to inflammatory bowel disease (IBD) is frequent when evaluating a patient with IBD and pulmonary involvement remains complicated. Most of the patients are asymptomatic and the methods used are mostly invasive or expensive procedures. The aim of this prospective study is to evaluate the value of the fractional exhaled nitric oxide (FENO) level for the diagnosis of pulmonary involvement due to IBD and to investigate any correlation between FENO level and disease activity. Methods: Thirty-three nonsmoker patients with IBD (25 ulcerative colitis [UC] and 8 Crohn's Disease [CD]) who were free of corticosteroid treatment and 25 healthy subjects as a control group were enrolled in this study. All patients with IBD were investigated for pulmonary involvement with medical history, physical examination, chest roentgenogram, oxygen saturation, blood eosinophil levels, pulmonary function tests (PFTs), high-resolution computed tomography (HRCT), and FENO level. Results: Pulmonary involvement was established in 15 patients (45.5%) with IBD. The FENO level was higher in patients with pulmonary involvement than without pulmonary involvement and healthy controls independent from the pulmonary symptoms, eosinophil count, duration of disease, activity of disease, and surgery history (FENO: 32 ± 20; 24 ± 8; 14 ± 8 ppb, respectively) (P < 0.05). In addition, diffusion capacity (DLCO) was found to be significantly lower in patients with CD compared with UC (P < 0.05). Conclusions: This study showed that an increased FENO level may be used for identifying patients with IBD who need further pulmonary evaluation. Inflamm Bowel Dis 2009 [source] Similar geographic variations of mortality and hospitalization associated with IBD and Clostridium difficile colitisINFLAMMATORY BOWEL DISEASES, Issue 3 2010Amnon Sonnenberg MD Abstract Background: Superinfection with Clostridium difficile can aggravate the symptoms of preexisting inflammatory bowel disease (IBD). The study served to assess whether the geographic variation of IBD within the United States might be influenced by C. difficile infection. Methods: Hospitalization data of the Healthcare Cost and Utilization Project (HCUP) from 2001,2006 and mortality data from 1979,2005 of the US were analyzed by individual states. Hospitalization and mortality associated with Crohn's disease (CD), ulcerative colitis (UC), and C. difficile colitis were correlated with each other, using weighted least square linear regression with the population size of individual states as weight. Results: Among the hospitalization rates, there were strong correlations between both types of IBD, as well as each type of IBD with C. difficile colitis. Similarly, among the mortality rates there were strong correlations between both types of IBD, as well as each type of IBD with C. difficile colitis. Lastly, each type of hospitalization rate was also strongly correlated with each type of mortality rate. In general, hospitalization and mortality associated with IBD tended to be frequent in many of the northern states and infrequent in the Southwest and several southern states. Conclusions: The similarity in the geographic distribution of the 3 diseases could indicate the influence of C. difficile colitis in shaping the geographic patterns of IBD. It could also indicate that shared environmental risk factors influence the occurrence of IBD, as well as C. difficile colitis. (Inflamm Bowel Dis 2010) [source] Does primary sclerosing cholangitis impact quality of life in patients with inflammatory bowel disease?INFLAMMATORY BOWEL DISEASES, Issue 3 2010Ashwin N. Ananthakrishnan MD Abstract Background: Impairment of health-related quality of life (HRQoL) is an important concern in inflammatory bowel disease (IBD; ulcerative colitis [UC], Crohn's disease [CD]). Between 2%,10% of patients with IBD have primary sclerosing cholangitis (PSC). There has been limited examination of the disease-specific HRQoL in this population compared to non-PSC IBD controls. Methods: This was a retrospective, case,control study performed at a tertiary referral center. Cases comprised 26 patients with a known diagnosis of PSC and IBD (17 UC, 9 CD). Three random controls were selected for each case after matching for IBD type, gender, age, and duration of disease. Disease-specific HRQoL was measured using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ). Disease activity for CD was measured using the Harvey,Bradshaw index (HB) and using the UC activity index for UC. Independent predictors of HRQoL were identified. Results: There was no significant difference in the age, gender distribution, or disease duration between PSC-IBD and controls. There was no difference in use of immunomodulators or biologics between the 2 groups. Mean SIBDQ score was comparable between PSC-IBD patients (54.5) and controls (54.1), both for UC and CD. Likewise, the disease activity scores were also similar (2.8 versus 3.1, P = 0.35). On multivariate analysis, higher disease activity score (,1.33, 95% confidence interval [CI] 95% CI ,1.85 to ,0.82) and shorter disease duration were predictive of lower HRQoL. Coexisting PSC did not influence IBD-related HRQoL. There was a higher proportion of permanent work disability in PSC-IBD (7.7%) compared to controls (0%). Conclusions: PSC does not seem to influence disease-specific HRQoL in our patients with IBD but is associated with a higher rate of work disability. (Inflamm Bowel Dis 2010) [source] Distribution of peroxisome proliferator,activated receptor,gamma polymorphisms in Chinese and Dutch patients with inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 2 2010Umid Kumar Shrestha Abstract Background: As peroxisome proliferator,activated receptor,gamma (PPAR-,) is frequently expressed in colon, its genetic polymorphism may play a role in the etiology of inflammatory bowel disease (IBD). The aims of the present study were to determine the distribution of PPAR-, polymorphisms Pro12Ala and C161T and to explore the association between the PPAR-, genotypes and phenotypes of IBD patients. Methods: A total of 244 IBD patients [212 ulcerative colitis (UC) and 32 Crohn's disease (CD)] and 220 controls in the Chinese population and 603 IBD patients (302 UC and 301 CD) and 180 controls in the white Dutch population were enrolled in the study. The phenotypes of Chinese IBD patients were grouped according to disease location. The PPAR-, polymorphisms Pro12Ala and C161T were genotyped by PCR-based methods. Results: In the Chinese population, T carriers of the PPAR-, C161T polymorphism were more common in UC patients than in the controls [37.7% vs. 25.5%, odds ratio 1.77, 95% confidence interval 1.18,2.68, P = 0.007], whereas Ala carriers of the Pro12Ala polymorphism showed no significant association in UC patients, but there was a significant association of Ala carriers with more extensive disease among the UC patients (P = 0.002); Pro12Ala and C161T genotypes did not show any associations with CD patients. No associations were found for the PPAR-, C161T SNP studied in the Dutch IBD population. Conclusions: Our study showed the potential association between the PPAR-, C161T polymorphism and UC patients in the central Chinese population. This finding was not replicated in the Dutch population. Further studies are necessary to explore the functional implication of the PPAR-, C161T polymorphism in Chinese UC patients. (Inflamm Bowel Dis 2009;) [source] Validity, reliability, and responsiveness of the EQ-5D in inflammatory bowel disease in GermanyINFLAMMATORY BOWEL DISEASES, Issue 1 2010Renee G. Stark MD Abstract Background: The EuroQol (EQ)-5D questionnaire is a generic instrument measuring health-related quality of life. Its validity, reliability, and responsiveness were assessed in a large sample of Crohn's disease (CD) and ulcerative colitis (UC) patients. Methods: The EQ-5D was completed initially (270 CD and 232 UC subjects) and after 4 weeks (447 subjects) with a transition question rating health change. Responsiveness of EQ visual analog scale (EQ-VAS) and the United Kingdom (UK-index) and German EQ-5D index (EQ-index) scores to reported changes in health was evaluated by standardized response means (SRM) and meaningful differences (MDs). Results: EQ-VAS and EQ-index scores correlated well with disease activity indices and differed significantly between active disease and remission groups. All scores were reliable in test,retest (ICC: EQ-VAS: 0.89; UK-index: 0.76; German EQ-index: 0.72). According to SRM, EQ-VAS was more responsive for deterioration in health than for improvement in health and was more responsive than index scores. Index scores were most responsive for deterioration in health in subjects in remission and for improved health in subjects with active disease. MDs for improved health (EQ-VAS: 10.9; UK EQ-index: 0.076; German EQ-index: 0.050) and deteriorated health (EQ-VAS: ,14.4; UK EQ-index: ,0.109; German EQ-index: ,0.067) were significant, but MD of EQ-VAS also differed significantly according to disease activity. Conclusions: The EQ-5D generates valid, reliable, and responsive preference-based valuations of health in CD and UC. EQ-VAS scores were more responsive than EQ-5D index scores. Thus, small health differences that are important from the patient's perspective may not be reflected in the EQ-index. Inflamm Bowel Dis 2010 [source] World Gastroenterology Organization Practice Guidelines for the Diagnosis and Management of IBD in 2010INFLAMMATORY BOWEL DISEASES, Issue 1 2010Dr. Charles N. Bernstein Chairman Abstract Inflammatory bowel disease (IBD) represents a group of idiopathic, chronic, inflammatory intestinal conditions. Its two main disease categories are: Crohn's disease (CD) and ulcerative colitis (UC), which feature both overlapping and distinct clinical and pathological features. While these diseases have, in the past, been most evident in the developed world, their prevalence in the developing world has been gradually increasing in recent decades. This poses unique issues in diagnosis and management which have been scarcely addressed in the literature or in extant guidelines. Depending on the nature of the complaints, investigations to diagnose either form of IBD or to assess disease activity will vary and will also be influenced by geographic variations in other conditions that might mimic IBD. Similarly, therapy varies depending on the phenotype of the disease being treated and available resources. The World Gastroenterology Organization has, accordingly, developed guidelines for diagnosing and treating IBD using a cascade approach to account for variability in resources in countries around the world. Inflamm Bowel Dis 2010 [source] Low bone mineral density in children and adolescents with inflammatory bowel disease: A population-based study from Western SwedenINFLAMMATORY BOWEL DISEASES, Issue 12 2009Susanne Schmidt MD Abstract Background: Low bone mineral density (BMD) has been recognized as a potential problem in children with inflammatory bowel disease (IBD). The aim of the study was to investigate BMD in Swedish children and adolescents with IBD and to evaluate possible factors affecting BMD. Methods: To evaluate BMD, all patients (n = 144) underwent a dual-energy X-ray absorptiometry (DXA) of the whole body and the spine. BMD values were expressed as Z-scores using normative pediatric data from Lunar (GE Medical Systems). Results: In this population-based study, the lowest BMD values were found in the lumbar spine. The entire IBD group showed significantly lower BMD Z-scores of the lumbar spine (L2,L4) in comparison to healthy references (,0.8 standard deviation [SD], range ,5.9 to 3.7 SD, P < 0.001). Decreased BMD with a Z-score < ,1 SD occurred in 46.7% of the individuals with Crohn's disease (CD) and in 47.0% of those with ulcerative colitis (UC). Low BMD with a Z-score , ,2 SD was present in 26.7% of the patients with CD and in 24.1% of the UC patients. In a multiple regression model with BMD lumbar spine as the depending variable, possible factors associated with lower BMD were male gender, low body mass index (BMI), and treatment with azathioprine. Conclusions: Low BMD is prevalent in Swedish pediatric patients with IBD. Possible risk factors for lower BMD are male gender, low BMI, and treatment with azathioprine, as a probable marker of disease course severity. (Inflamm Bowel Dis 2009) [source] Ulcerative colitis: Correlation of the Rachmilewitz endoscopic activity index with fecal calprotectin, clinical activity, C-reactive protein, and blood leukocytesINFLAMMATORY BOWEL DISEASES, Issue 12 2009Alain M. Schoepfer MD Abstract Background: The accuracy of noninvasive markers for the detection of endoscopically active ulcerative colitis (UC) according the Rachmilewitz Score is so far unknown. The aim was to evaluate the correlation between endoscopic disease activity and fecal calprotectin, Clinical Activity Index, C-reactive protein (CRP), and blood leukocytes. Methods: UC patients undergoing colonoscopy were prospectively enrolled and scored independently according the endoscopic and clinical part of the Rachmilewitz Index. Patients and controls provided fecal and blood samples for measuring calprotectin, CRP, and leukocytes. Results: Values in UC patients (n = 134) compared to controls (n = 48): calprotectin: 396 ± 351 versus 18.1 ± 5 ,g/g, CRP 16 ± 13 versus 3 ± 2 mg/L, blood leukocytes 9.9 ± 3.5 versus 5.4 ± 1.9 g/L (all P < 0.001). Endoscopic disease activity correlated closest with calprotectin (Spearman's rank correlation coefficient r = 0.834), followed by Clinical Activity Index (r = 0.672), CRP (r = 0.503), and leukocytes (r = 0.461). Calprotectin levels were significantly lower in UC patients with inactive disease (endoscopic score 0,3, calprotectin 42 ± 38 ,g/g), compared to patients with mild (score 4,6, calprotectin 210 ± 121 ,g/g, P < 0.001), moderate (score 7,9, calprotectin 392 ± 246 ,g/g, P = 0.002), and severe disease (score 10,12, calprotectin 730 ± 291 ,g/g, P < 0.001). The overall accuracy for the detection of endoscopically active disease (score ,4) was 89% for calprotectin, 73% for Clinical Activity Index, 62% for elevated CRP, and 60% for leukocytosis. Conclusions: Fecal calprotectin correlated closest with endoscopic disease activity, followed by Clinical Activity Index, CRP, and blood leukocytes. Furthermore, fecal calprotectin was the only marker that reliably discriminated inactive from mild, moderate, and highly active disease, which emphasizes its usefulness for activity monitoring. Inflamm Bowel Dis 2009 [source] Inflammatory bowel disease in the setting of autoimmune pancreatitis,INFLAMMATORY BOWEL DISEASES, Issue 9 2009Karthik Ravi MD Abstract Background: Despite scattered case reports, the prevalence of inflammatory bowel disease (IBD) in patients with autoimmune pancreatitis (AIP) is unknown. We sought to better characterize the putative association between the conditions. Methods: Medical records of 71 patients meeting accepted criteria for AIP were reviewed to identify those with endoscopic and histological evidence of IBD. Colon samples in patients with both AIP and IBD were immunostained to identify IgG4-positive cells. Results: Four patients with AIP (5.6%) had a diagnosis of IBD: 3 had ulcerative colitis (UC) and 1 had Crohn's disease (CD). The diagnosis of IBD preceded or was simultaneous to that of AIP. Two AIP-UC patients treated for AIP with prednisone had a recurrence of AIP, and 1 required 6-mercaptopurine for long-term corticosteroid-sparing treatment. Two AIP-IBD patients underwent Whipple resections, and 1 had recurrent AIP. All 3 patients with UC presented with pancolitis, and 2 required colectomy. Colon samples from 1 patient with UC and 1 patient with CD were available for review. Increased numbers of IgG4-positive cells (10 per high-power field) were noted on the colon sample from the patient with UC. Conclusions: Almost 6% of patients with proven AIP had a diagnosis of IBD, compared to a prevalence of ,0.4%,0.5% in the general population, potentially implying a 12,15-fold increase in risk. Patients with both AIP and IBD may have increased extent and severity of IBD. The finding of IgG4-positive cells on colon biopsy suggests that IBD may represent an extrapancreatic manifestation of AIP. (Inflamm Bowel Dis 2009) [source] Human neutrophil peptides 1,3 are useful biomarkers in patients with active ulcerative colitisINFLAMMATORY BOWEL DISEASES, Issue 6 2009Shuji Kanmura MD Abstract Background: A specific useful biomarker for diagnosing ulcerative colitis (UC) has not yet been described. This study employed proteomics to identify serum protein biomarkers for UC. Methods: Ninety-four blood samples were isolated from patients and controls (including 48 UC, 22 Crohn's disease [CD], 5 colorectal cancer, and 6 infectious colitis patients and 13 healthy subjects). Serum samples were analyzed using the SELDI-TOF/MS ProteinChip system. After applying the samples to ProteinChip arrays, we assessed differences in the proteomes using Ciphergen ProteinChip software and identified candidate proteins, which were then characterized in immunoassays. Results: Preliminary analysis using the ProteinChip system revealed significant peak-intensity differences for 27 serum proteins between 11 patients with UC and 7 healthy subjects. Among these proteins, 3 proteins (with mass/charge ratios of approximately 3400) were identified as human neutrophil peptides 1,3 (HNP 1,3). The presence of HNP 1,3 in the patient sera was confirmed using immunoassays. Enzyme-linked immunosorbent assays demonstrated that the mean plasma concentration of HNP 1,3 was significantly higher in patients with active UC (n = 28) than in patients whose UC was in remission (n = 20) or patients with CD (n = 22), infectious colitis, or healthy subjects, and tended to be higher than in patients with colon cancer. In addition, the plasma concentration of HNP 1,3 in patients that responded to corticosteroids-based therapy decreased after treatment, whereas it was not changed in nonresponders. Conclusions: HNP 1,3 is a novel biomarker that may be useful for diagnosing patients with active UC and predicting treatment outcomes. (Inflamm Bowel Dis 2008) [source] GlcNAc6ST-1-mediated decoration of MAdCAM-1 protein with L-selectin ligand carbohydrates directs disease activity of ulcerative colitisINFLAMMATORY BOWEL DISEASES, Issue 5 2009Motohiro Kobayashi MD Abstract Background: A diffuse lymphocyte infiltrate is 1 of the characteristic features of ulcerative colitis (UC). Such lymphocyte recruitment requires lymphocyte rolling mediated by L-selectin ligand carbohydrates (6-sulfo sialyl Lewis X-capped O -glycans) and/or mucosal addressin cell adhesion molecule 1 (MAdCAM-1) expressed on high endothelial venule (HEV)-like vessels. The present study was undertaken to elucidate the role of MAdCAM-1 posttranslationally modified ("decorated") with L-selectin ligand carbohydrates in UC pathogenesis and consequent clinical outcomes. Methods: Biopsy specimens composed of active and remission phases of UC as well as normal colonic mucosa were immunostained for CD34, MAdCAM-1, and MECA-79, and the immunostained sections were quantitatively analyzed. Reverse-transcriptase polymerase chain reaction (RT-PCR) was carried out to evaluate transcripts of MAdCAM-1 and N -acetylglucosamine-6- O -sulfotransferases (GlcNAc6STs). CHO and Lec2 cells transfected with CD34 and MAdCAM-1 together with enzymes involved in L-selectin ligand carbohydrate biosynthesis were analyzed by immunofluorescence, FACS, and Western blotting to characterize the biochemical properties of GlcNAc6STs. Results: The number of MAdCAM-1+ vessels was increased in UC, with no significant difference between active and remission phases. An increased ratio of MECA-79+ to MAdCAM-1+ vessels with preferential GlcNAc6ST-1 transcripts was observed in the active phase of UC compared to the remission phase. MAdCAM-1 protein was colocalized with L-selectin ligand carbohydrates at the luminal surface of HEV-like vessels in situ. GlcNAc6ST-1 preferentially utilizes MAdCAM-1 as a scaffold protein for GlcNAc-6- O -sulfation in L-selectin ligand carbohydrate biosynthesis. Conclusions: UC disease activity is not regulated by expression of MAdCAM-1 protein itself, but rather by GlcNAc6ST-1-mediated decoration of MAdCAM-1 protein with L-selectin ligand carbohydrates. (Inflamm Bowel Dis 2008) [source] Probiotic preparation VSL#3 induces remission in children with mild to moderate acute ulcerative colitis: A pilot studyINFLAMMATORY BOWEL DISEASES, Issue 5 2009Hien Q. Huynh MD Abstract Background: Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD) that has periods of exacerbated symptoms and periods that are symptom-free. The treatment of active UC with probiotic bacteria could possibly induce remission. We evaluated the clinical efficacy and safety profile of probiotic preparation VSL#3 in the treatment of mild to moderate acute UC in the pediatric population. Methods: Eighteen eligible patients between the ages of 3,17 with mild to moderate acute UC received open-label VSL#3 daily in 2 divided doses for 8 weeks. The disease activity pre- and post-VSL#3 therapy was assessed by the simple clinical colitis activity index (SCCAI); Mayo ulcerative colitis endoscopic score; inflammatory markers: erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP); serum cytokine profiling; and rectal tissue microbial profiling done at baseline and at week 8. Results: Thirteen patients completed 8 weeks of VSL#3 treatment and 5 patients were withdrawn due to lack of improvement. Remission (defined as SCCAI ,3) was achieved in 56% of children (n = 10); response (decrease in SCCAI ,2, but final score ,5) in 6% (n = 1); and no change or worsening in 39% (n = 7). Post-VSL#3 treatments demonstrated a bacterial taxonomy change in rectal biopsy. The VSL#3 was well tolerated in clinical trials and no biochemical and clinical adverse effects attributed to VSL#3 were identified. Conclusions: Treatment of pediatric patients diagnosed with mild to moderate UC with VSL#3 resulted in a remission rate of 56% and a combined remission/response rate of 61%. (Inflamm Bowel Dis 2008) [source] Validation of interactive voice response system administration of the short inflammatory bowel disease questionnaireINFLAMMATORY BOWEL DISEASES, Issue 4 2009Manuel Y. Lam BA Abstract Background: The Short Inflammatory Bowel Disease Questionnaire (SIBDQ) is a written, self-administered instrument measuring quality of life in IBD. We assessed the validity of an interactive voice response system (IVRS) as a new mode of administering the SIBDQ. Methods: An IVRS was designed using prerecorded questions to collect data via touchtone telephone. Subjects with Crohn's disease (CD) or ulcerative colitis (UC) were randomized into 2 groups with different orders of administration: written, self-administered followed by IVRS (S-I) or IVRS followed by written, self-administered (I-S). Half of the S-I group was also randomized to receive a second IVRS. Sixty-four subjects were studied: 30 in S-I, 34 in I-S. Results: The mean SIBDQ scores were not different between written and IVRS modes (P = 0.26) with r = 0.93. IVRS scores were lower in active than inactive CD (36.1 ± 9.6 versus 54.7 ± 8.6, P < 0.001) and lower in active than inactive UC (40.8 ± 9.6 versus 59.8 ± 10.0, P < 0.001). Mean scores correlated highly with disease activity indices, and were not different between first and second IVRS administrations (P = 0.85) with r = 0.92. IVRS had excellent internal consistency (Cronbach alpha = 0.90). Conclusions: IVRS administration of the SIBDQ yields results similar to written self-administration, with excellent procedural validity, test,retest reliability, and internal consistency. (Inflamm Bowel Dis 2009) [source] | |||||||||||||||||||||||||||||||