Anti-Enteric Neuronal Antibodies and the Irritable Bowel Syndrome

Background/AimsFunctional gastrointestinal disorders are those in which no abnormal metabolic or physical processes, which can account for the symptoms, can be identified. The irritable bowel syndrome (IBS) is a significant functional disorder, which affects 10-20 percent of the population worldwide. Predominant symptoms of IBS are abnormal defecation associated with abdominal pain, both of which may be exacerbated by psychogenic stress. Our study was designed to test a hypothesis that symptoms in a subset of patients with a diagnosis of IBS are associated with an autoimmune degenerative neuropathy in the enteric nervous system.MethodsSerum was collected from Rome II-IBS patients and controls at the University of North Carolina Functional Gastrointestinal Diseases Center. Assay procedures were immunohistochemical localization of antibody binding to enteric neurons and human protein microarray assay for antigens recognized by antibodies in the sera.ResultsEighty-seven percent of IBS sera and 59% of control sera contained anti-enteric neuronal antibodies. Antibody immunostaining was seen in the nucleus and cytoplasm of neurons in the enteric nervous system. Protein microarray analysis detected antibody reactivity for autoantigens in serum with anti-enteric neuronal antibodies and no reactivity for the same autoantigens in samples not containing anti-enteric neuronal antibodies in our immunostaining assay. Antibodies in sera from IBS patients recognized only 3 antigens out of an 8,000 immunoprotein array. The 3 antigens were: (1) a nondescript ribonucleoprotein (RNP-complex); (2) small nuclear ribonuclear polypeptide A; and (3) Ro-5,200 kDa.ConclusionsResults of the present study suggest that symptoms in a subset of IBS patients might be a reflection of enteric neuronal damage or loss, caused by circulating anti-enteric autoimmune antibodies

Does psychological status influence clinical outcomes in patients with inflammatory bowel disease (IBD) and other chronic gastroenterological diseases: An observational cohort prospective study

Background: Whether there is a temporal relationship between psychological problems and clinical outcomes in patients with diseases of the digestive tract has not been widely researched. Thus, our aims were 1) To observe and compare prospectively clinical outcomes in relation to psychological co-morbidity in patients with inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and chronic hepatitis C (HCV) and, 2) To test the hypothesis that patients with psychological co-morbidities are less likely to have a satisfactory response to standard treatment at 12 months. Methods: Overall, 139 patients were enrolled in this observational cohort prospective study. Over the ensuing year, physical and psychological measures were made at baseline and after 12 months (HADS, SCL90, SF-12 and disease activity measures). A logistic regression was conducted to observe any relationship between baseline characteristics and patients' clinical outcomes after 12 months. Results: Overall, there was no relationship between psychological status and quality of life at baseline and relapse at 12 months (p > 0.05). However, patients with inactive disease at baseline were at lower risk of relapse after 12 months (OR = 0.046, CI: 0.012–0.178). No significant relationship was found between psychological problems such as depression/anxiety and a total number of relapses in the IBD group. However, interestingly, patients with an active disease at baseline tended to have a greater number of relapses (OR = 3.07, CI: 1.650–5.738) and CD participants were found at lower risk of relapse than UC participants (OR = 0.382, CI: 0.198–0.736). Conclusion: In contrast to previous investigations, this study suggests that there is no temporal relationship between psychological problems at baseline and clinical outcomes over time. Longer and larger prospective studies are needed to better understand this result.Antonina A Mikocka-Walus, Deborah A Turnbull, Nicole T Moulding, Ian G Wilson, Gerald J Holtmann and Jane M Andrew

The EQ-5D (Euroqol) is a valid generic instrument for measuring quality of life in patients with dyspepsia

<p>Abstract</p> <p>Background</p> <p>There is little information of the validity of generic instruments in measuring health-related quality of life (HRQOL) in patients with dyspepsia. We aimed to assess the reliability and validity of the EQ-5D, a brief and simple instrument, in measuring HRQOL in adult patients with dyspepsia.</p> <p>Methods</p> <p>Consecutive adults with dyspepsia attending the Gastroenterology clinic in a tertiary referral center were interviewed with the EQ-5D (both English and Malay versions), the short-form Nepean Dyspepsia Index (SF-NDI), the SF-36 and Leeds Dyspepsia Questionnaire (LDQ). Known-groups and convergent construct validity were investigated by testing hypotheses at attribute and overall levels. A repeat telephone interview was conducted 2 weeks later to assess test-retest reliability.</p> <p>Results</p> <p>A total of 113 patients (mean (SD) age: 53.7 (14) years; 49.5% male; 24.8% Malays, 37.2% Chinese; 70.8% functional dyspepsia) were recruited. Response rate was 100% with nil missing data. Known-groups validation revealed 20/26 hypotheses fulfillment. Patients with more severe dyspepsia reported more problems with their usual activity (p = 0.07) and pain (p = 0.06) and demonstrated lower median VAS scores (60 vs 70, p = 0.002) and EQ-5D utility scores (0.72 vs 0.78, p = 0.002). Those reporting problems in various EQ-5D dimensions had significantly lower scores in relevant SF-36 and SF-NDI dimensions. The overall EQ-5D utility score also demonstrated good correlation with the SF-36 summary physical and mental scores and the SF-NDI total score. Intraclass correlation coefficient for test-retest reliability was 0.66 (95% CI = 0.55 – 0.76).</p> <p>Conclusion</p> <p>The EQ-5D is an acceptable, valid and reliable generic instrument for measuring HRQOL in adult patients with dyspepsia.</p

Quality of life in South East Asian patients who consult for dyspepsia: Validation of the short form Nepean Dyspepsia Index

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Surgical Outcomes after Total Colectomy with Ileorectal Anastomosis in Patients with Medically Intractable Slow Transit Constipation

Purpose: The aim of this study was to evaluate outcomes of a total colectomy with ileorectal anastomosis in patients with slow transit constipation. Methods: A retrospective review of 37 consecutive patients with slow transit constipation who underwent a total colectomy between 1994 and 2008 was undertaken. Preoperative and postoperative Wexner’s constipation scores were collected and used to evaluate the outcomes after surgical treatment. Also patients ’ postoperative satisfaction scores were collected using a 4-point scale. Results: The 37 patients consisted of 31 women and 6 men, with a median age of 41 years (range, 17 to 71 years). Pre- and post-operative Wexner’s scores were collected from 33 patients (89.1%), and the mean preoperative Wexner’s score was 19.3 (range, 11 to 24), which decreased to an average post-operative score of 2.3 (range, 0 to 8). Neither intraoperative complications nor postoperative mortalities were noted. Five patients (13.5%) had early postoperative complications, and the most common complication was postoperative ileus (10.8%). Seven patients (18.9%) had late postoperative complications, and postoperative ileus (10.8%) was also the most common. Twenty seven of 33 patients were satisfied with their surgical outcome (81.8%). Conclusion: A total colectomy with ileorectal anastomosis might be an effective surgical procedure with acceptable morbidity to treat medically intractable slow transit constipation

The G-Protein β3 subunit 825 TT genotype is associated with epigastric pain syndrome-like dyspepsia

<p>Abstract</p> <p>Background</p> <p>Although familial clustering of functional dyspepsia (FD) has been reported, the role of genetics in the susceptibility to FD is still not well understood. Several reports indicate an association between FD and G-protein β3 (GNB3) subunit gene polymorphism (C825T); however, these studies had small sample sizes and the findings are inconclusive. In the present study we clarified the association between GNB3 gene polymorphism and dyspepsia in a large population of Japanese subjects who visited a hospital for annual health check-up.</p> <p>Methods</p> <p>Subjects with significant upper gastrointestinal findings were excluded. Subjects with dyspeptic symptoms were divided into either a postprandial distress syndrome (PDS) group or an epigastric pain syndrome (EPS) group according to the Rome III criteria. The presence of the GNB3 C825T polymorphism was then evaluated and logistic regression analysis was used to test all variables.</p> <p>Results</p> <p>The GNB3 genotype distribution in subjects without dyspepsia was 191 CC (25.1%), 368 TC (48.4%), and 202 TT (26.5%) and 17 CC (25.0%), 29 TC (42.6%), and 22 TT (32.4%) in subjects with dyspepsia. No significant correlation was found between the GNB3 825TT genotype and dyspepsia. However, the TT genotype was significantly associated with subjects with EPS-like symptoms (odds ratio (OR) = 2.00, 95% confidence interval (CI); 1.07-3.76) compared to the CT/CC genotype adjusted for gender and age. No significant correlation was found between GNB3 polymorphism and PDS-like symptoms (OR = 0.68, 95% CI; 0.31-1.51). With the exclusion of subjects with both EPS- and PDS-like symptoms, only the TT genotype was significantly associated with EPS-like symptoms (OR = 2.73, 95% CI; 1.23-5.91).</p> <p>Conclusion</p> <p>The homozygous GNB3 825T allele influences the susceptibility to EPS-like dyspepsia.</p