Fecal Calprotectin, CRP and Leucocytes in IBD Patients: Comparison of Biomarkers With Biopsy Results.

BACKGROUND: This study aimed to compare fecal calprotectin (FC) levels with other commonly used parameters as part of patient care during evaluation for inflammatory bowel disease (IBD). METHODS: We recruited adult IBD patients with ulcerative colitis (UC) and Crohn's disease (CD) and compared the results of the patient's biopsy results (i.e., inflamed versus noninflamed) for six sites (i.e., ileum, ascending colon, transverse colon, descending colon, sigmoid colon, rectum) with concentrations of C-reactive protein (CRP), total leucocytes and fecal calprotectin (FC). RESULTS: We found that FC was significantly elevated in a concentration-dependent manner that correlated with the number of active inflammation sites reported in biopsy. Although CRP and leucocyte measurements trended upwards in line with inflammation reported from biopsy, the results were highly variable and highlighted poor reliability of these biomarkers for indicating IBD inflammation. CONCLUSIONS: These results strongly suggest that FC correlates best with biopsy reports and is a superior marker than CRP and leucocytes.

Characterization of Serotonin Signaling Components in Patients with Inflammatory Bowel Disease.

BACKGROUND: Tryptophan hydroxylase (TPH)1 catalyzes the biosynthesis of serotonin (5-hydroxytrptamine; 5-HT) in enterochromaffin (EC) cells, the predominant source of gut 5-HT. Secreted 5-HT regulates various gut functions through diverse 5-HT receptor (5-HTR) families, and 5-HT transporter (5-HTT) sequesters its activity via uptake into surrounding cells. In inflammatory bowel disease (IBD) mucosal 5-HT signaling is altered, including upregulated EC cell numbers and 5-HT levels. We examined key mucosal 5-HT signaling components and blood 5-HT levels and, as part of a pilot study, investigated the association between 5-HTT gene-linked polymorphic region (5HTTLPR) and Crohn's disease (CD). METHODS: In the context of inflammation, colonic expressions of TPH1, 5-HTT and 5-HTRs were studied in CD patients (n=15) and healthy controls (HC; n=10) using quantitative polymerase chain reaction (qPCR). We also investigated 5HTTLPR in 40 CD patients and HC utilizing PCR and measured platelet-poor plasma (PPP) and plasma 5-HT concentrations. RESULTS: Compared with HC, inflammation in CD patients was associated with elevated TPH1, 5-HTR3, 5-HTR4, 5-HTR7 and downregulated 5-HTT expressions. In our second cohort of participants, significantly higher PPP and plasma 5-HT levels and higher S-genotype (L/S+S/S) than L/L genotype were observed in CD patients compared with HC. CONCLUSION: Our results suggest that augmented mucosal 5-HT signaling and specific 5-HTTLPR genotype-associated decreased efficiency in 5-HT reuptake, the latter through increased 5-HT availability, may contribute to inflammation in CD patients. These findings revealed important information on various components of 5-HT signaling in intestinal inflammation which may ultimately lead to effective strategies targeting this pathway in IBD.

Functional Dyspepsia: A New Rome III Paradigm.

Functional dyspepsia (FD) is a condition commonly seen in gastroenterological practice. With the introduction of Rome III criteria in 2006, a new approach for categorizing patients has been recommended. The diagnostic criteria suggest that meal-related and pain-predominant symptom groupings that presumably have distinct pathophysiologic mechanisms and potentially different therapeutic targets exist. The new classification is in the early stages of testing; in the meantime, the umbrella term of FD should continue to be utilized in clinical practice. Treatment of FD remains a major challenge. Unfortunately, most of the agents used in practice have limited or no evidence of efficacy, and the results typically are short-lived once therapy is ceased. Appropriate therapy currently is based on a consideration of putative pathophysiologic mechanisms. Testing for and eradicating Helicobacter pylori is a first-line strategy irrespective of the symptom pattern. In patients who have epigastric pain, antisecretory agents are recommended. Antacids, bismuth, and sucralfate seem to be no better than placebo. For meal-related symptoms such as postprandial fullness or early satiety, prokinetics may confer some benefit. However, few choices are available, and the efficacy for those drugs on the market is limited at best. Antidepressants are of uncertain efficacy but are widely used. Psychological therapies seem promising and may confer benefits on both pain and meal-related symptoms. Efficacy of complementary medicines has been suggested in controlled trials, but more data are needed. Emerging treatments include gastric fundus relaxors and visceral analgesics, although their application in FD is still in the preliminary stages.

Natural history of functional gastrointestinal disorders: a 12-year longitudinal population-based study.

BACKGROUND & AIMS: Functional gastrointestinal disorders (FGID) are common in the community. The natural history of FGID is unknown because of a lack of prospective population-based studies and the indistinct nature of the phenotype. We sought to report the natural history of FGID in a US population. METHODS: This prospective cohort study used data from multiple validated surveys of random samples of Olmsted County, MN, residents over a mean of a 12-year period between 1988 and 2003 (n = 1365). The surveys measured gastrointestinal symptoms experienced during the past year. Each subject received a minimum of 2 surveys. Point prevalence, onset, and disappearance rates and transition probabilities were calculated for individual FGIDs. RESULTS: Between the initial and final surveys, the point prevalences (per 100 residents) were stable for irritable bowel syndrome (8.3% and 11.4%, respectively) and functional dyspepsia (1.9% and 3.3%, respectively). The onset of each of the disorders studied was greater than the disappearance rate, but the transition probabilities varied across the different subgroups. Among people with symptoms at baseline, approximately 20% had the same symptoms, 40% had no symptoms, and 40% had different symptoms at follow-up. CONCLUSIONS: Although the prevalence of the FGID was stable over time, the turnover in symptom status was high. Many episodes of symptom disappearance were due to subjects changing symptoms rather than total symptom resolution. This transition between different FGIDs suggests a common etiopathogenesis.

Treatment of functional dyspepsia.

Functional dyspepsia (FD) is a common reason a patient presents with upper gastrointestinal symptoms for medical care. Although treatment of FD remains expensive, the agents are rarely used in a systematic manner; the majority of treatments are empirical and the results short lived once therapy is ceased. This is partly due to the lack of consistent pathophysiologic markers in FD, so therapy is symptom driven. This review appraises the best evidence on available interventions. A structured scheme for deciding on appropriate therapies is to consider the possible putative pathophysiologic mechanisms. Eradicating Helicobacter pylori, if present, is a first-line strategy. In patients who have symptoms suggesting excessive gastric acid secretion, particularly epigastric pain, antisecretory agents are recommended. Prokinetics may confer benefits on symptoms suggestive of upper gastrointestinal dysmotility, like fullness or early satiety. However, their use is limited due to availability issues. The expanding field of psychologic therapies provides a promising avenue of treatment. Complementary medicines are now widely use and their benefits have been suggested in recent controlled trials. Emerging treatments include cholecystokinin 1 blockers, opioid receptor agonists, and serotonergic agents, although their application in FD is in the preliminary stages.

Psychosocial risk factors for the onset of abdominal pain. Results from a large prospective population-based study.

OBJECTIVE: To determine the psychosocial risk factors for the development of abdominal pain and to determine whether, in those people who consulted, symptoms had been attributed to an organic cause. DESIGN: Prospective population-based postal survey with follow-up survey at 12 months. SETTING: A mixed sociodemographic suburban area of Manchester, UK. PARTICIPANTS: Subjects aged 18-65 years were randomly selected from a population-based primary care register who had responded to a detailed pain questionnaire, which included a pain manikin drawing. They also completed the following psychosocial instruments: General Health Questionnaire, Somatic Symptom Checklist, Fatigue Questionnaire and the Illness Attitude Scales (including the 'health anxiety' and 'illness behaviour' sub-scales). MAIN OUTCOME MEASURES: The onset of new abdominal pain. RESULTS: Of the 1953 participants at baseline, 1763 were free of abdominal pain: 1551 were followed up at 12 months (adjusted follow-up rate of 92%) of which 69 subjects reported new abdominal pain (new onset rate 4.6%). New abdominal pain was similar in females (4.9%) and males (4.2%), and did not vary by age group. Baseline factors which predicted onset were high levels of fatigue (odds ratio [OR] = 3.3, 95% CI: 1.9-5.8), psychological distress (OR = 3.4, 95% CI: 1.9-6.0), high scores on the illness behaviour scale (OR = 3.3, 95% CI: 1.7-6.7) and high levels of health anxiety (OR = 2.1, 95% CI: 1.1-3.9). Reporting low back pain at baseline was also associated with an increased risk of reporting abdominal pain (OR = 2.0, 95% CI: 1.2-3.3). On multivariate analysis, high levels of psychological distress and aspects of prior illness behaviour were the major independent predictors of outcome. Of those who sought health care, only one consultation led to a definite diagnosis. CONCLUSION: In subjects free of abdominal pain, psychological distress, fatigue, health anxiety and illness behaviour are predictors of future onset rather than merely a consequence of symptoms. These results suggest that abdominal pain shares some common features of onset with pain at other sites thought not to be primarily organic in origin.