Identification of putative transcriptomic biomarkers in irritable bowel syndrome (IBS): Differential gene expression and regulation of TPH1 and SERT by vitamin D.

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders and affects approximately 4% of the global population. The diagnosis of IBS can be made based on symptoms using the validated Rome criteria and ruling out commonly occurring organic diseases. Although biomarkers exist for "IBS mimickers" such as celiac disease and inflammatory bowel disease (IBD), no such test exists for IBS. DNA microarrays of colonic tissue have been used to identify disease-associated variants in other gastrointestinal (GI) disorders. In this study, our objective was to identify biomarkers and unique gene expression patterns that may define the pathological state of IBS. Mucosal tissue samples were collected from the sigmoid colon of 29 participants (11 IBS and 18 healthy controls). DNA microarray analysis was used to assess gene expression profiling. Extraction and purification of RNA were then performed and used to synthesize cDNA. Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was employed to identify differentially expressed genes in patients diagnosed with IBS compared to healthy, non-IBS patient-derived cDNA. Additional testing probed vitamin D-mediated regulation of select genes associated with serotonergic metabolism. DNA microarray analyses led to the identification of 858 differentially expressed genes that may characterize the IBS pathological state. After screening a series of genes using a combination of gene ontological analysis and RT-qPCR, this spectrum of potential IBS biomarkers was narrowed to 23 genes, some of which are regulated by vitamin D. Seven putative IBS biomarkers, including genes involved in serotonin metabolism, were identified. This work further supports the hypothesis that IBS pathophysiology is evident within the human transcriptome and that vitamin D modulates differential expression of genes in IBS patients. This suggests that IBS pathophysiology may also involve vitamin D deficiency and/or an irregularity in serotonin metabolism.

A Pain in the Butt: Hemorrhoids, Fissures, Fistulas, and Other Anorectal Syndromes.

Painful and bothersome anorectal syndromes can be a diagnostic and therapeutic challenge for clinicians because structural and functional abnormalities may often coexist and require a multidisciplinary approach to management. Although it is often difficult to attribute all of a patient's anorectal symptoms to a singular disorder with definitive intervention and cure, improving quality of life, treating coexistent conditions such as functional constipation and/or defecation disorders, addressing psychological comorbidities if present, and confirming there is no evidence of inflammatory or malignant conditions are top priorities.

Diagnostic Evaluation of Gastric Motor and Sensory Disorders.

Disorders of gastric motor and sensory function affect 10%-20% of the world's population and adversely impact nutrition, quality of life, work productivity, and health care costs. Classifying these disorders can be challenging given the heterogeneity of symptom presentation, the presence of symptoms unexplained by endoscopic, radiographic and/or laboratory evaluation, and overlap with other luminal gastrointestinal disorders. Accurately diagnosing these highly prevalent disorders relies upon an understanding of epidemiology and risk factors, the ability to take a careful clinical history focused on symptoms, and the presence of predisposing medical, surgical, and psychological conditions. A variety of diagnostic studies are now available to assess gastric motor function and identify maladaptive relaxation, accommodation, and abnormal sensation. FDA-approved treatment options are limited and thus many patients undergo a series of empirical treatment trials that target individual symptoms, often without much benefit. This article provides updated recommendations for identifying and classifying the most common gastric motor and sensory disorders using currently accepted diagnostic tests, and provides a brief supplemental overview on treatment options. "Things sweet to taste prove in digestion sour." -Shakespeare, Richard II, 1595.

Evaluation and Treatment of Constipation in the Geriatric Population.

Chronic constipation affects one-third of the US population and occurs disproportionately in the elderly and female individuals, increasing in older individuals who are institutionalized. This condition has a significant impact on health care costs and quality of life. Clinicians need to consider primary as well as secondary causes of constipation in elderly individuals because the cause is often multifactorial. Diagnostic algorithms should eliminate red-flag symptoms that may indicate a malignancy but also consider pelvic floor dysfunction, which is more common in this age group. An appropriate treatment plan is tailored to the severity of the patient's symptoms.

YouTube™ as a Source of Instructional Videos on Bowel Preparation: a Content Analysis.

Instructional videos on bowel preparation have been shown to improve bowel preparation scores during colonoscopy. YouTube™ is one of the most frequently visited website on the internet and contains videos on bowel preparation. In an era where patients are increasingly turning to social media for guidance on their health, the content of these videos merits further investigation. We assessed the content of bowel preparation videos available on YouTube™ to determine the proportion of YouTube™ videos on bowel preparation that are high-content videos and the characteristics of these videos. YouTube™ videos were assessed for the following content: (1) definition of bowel preparation, (2) importance of bowel preparation, (3) instructions on home medications, (4) name of bowel cleansing agent (BCA), (5) instructions on when to start taking BCA, (6) instructions on volume and frequency of BCA intake, (7) diet instructions, (8) instructions on fluid intake, (9) adverse events associated with BCA, and (10) rectal effluent. Each content parameter was given 1 point for a total of 10 points. Videos with ≥5 points were considered by our group to be high-content videos. Videos with ≤4 points were considered low-content videos. Forty-nine (59 %) videos were low-content videos while 34 (41 %) were high-content videos. There was no association between number of views, number of comments, thumbs up, thumbs down or engagement score, and videos deemed high-content. Multiple regression analysis revealed bowel preparation videos on YouTube™ with length >4 minutes and non-patient authorship to be associated with high-content videos.

C-reactive protein and high-sensitivity C-reactive protein: an update for clinicians.

The measurement of C-reactive protein (CRP) using both standard and high-sensitivity CRP (hs-CRP) assays is becoming common in clinical practice. This article addresses the causes of CRP elevation and the use of different CRP assays in internal medicine, including cardiology, gastroenterology, rheumatology, infectious diseases, and oncology. We focus on the recent medical literature on the use of hs-CRP in cardiovascular disease risk stratification and management, including updated screening guidelines on the use of hs-CRP, such as those issued in 2009 by the Canadian Cardiovascular Society. We also discuss the Reynolds Risk Score, which incorporates hs-CRP and family history with more standard cardiovascular risk factors (eg, tobacco use, hypertension, and dyslipidemia) and frequently leads to improved recategorization of cardiovascular disease risk levels. As the recently completed Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) trial indicated that statin therapy decreases the vascular events among persons with elevated hs-CRP by half, even when cholesterol levels are low, the inclusion of information on hs-CRP values with other cardiovascular risk factors may assist physicians in medical decision making for patients.

Lubiprostone: evaluation of the newest medication for the treatment of adult women with constipation-predominant irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a chronic disorder that affects primarily female patients and is thought also to afflict approximately 7%-10% of the population of the Western World. Although bowel habits may change over the course of years, patients with IBS are characterized according to their predominant bowel habit, constipation (IBS-C), diarrhea (IBS-D), or mixed type (IBS-M), and treatments are focused toward the predominant symptom. Current treatments for IBS-C have included fiber, antispasmodics, osmotic and stimulant laxatives, and the now severely limited 5-HT(4) agonist tegaserod. No one agent has been universally successful in the treatment of this bothersome syndrome and the search for new agents continues. Lubiprostone (Amitiza(®)), a novel compound, is a member of a new class of agents called prostones and was approved for the treatment of chronic idiopathic constipation in 2006 at a dose of 24 µg twice daily and then in 2008 for the treatment of IBS-C in women only at a dose of 8 µg twice daily. Its purported mechanism is as a type 2 chloride channel activator, but recent evidence suggests that it may also work at the cystic fibrosis transport receptor. This article will compare the newly proposed mechanism of action of this compound to the purported mechanism and review the structure, pharmacology, safety, efficacy, and tolerability of this new therapeutic option. Clinical trial data leading to the approval of this agent for the treatment of IBS-C and the gender-based understanding of IBS, as well as this agent's place among existing and emerging therapies, will be examined.

Personality traits and impaired health-related quality of life in patients with functional gastrointestinal disorders.

BACKGROUND & AIMS: Negative affectivity and social isolation (Type D personality) are personality traits associated with poor health-related quality of life (HRQoL). We hypothesized these traits would be associated with impaired HRQoL and increased gastrointestinal symptom severity in functional gastrointestinal disorders. METHODS: Data were collected from patients undergoing breath testing. Patients completed the Type D Scale-14, Gastrointestinal Symptoms Severity Index and Short-Form Health Survey 12. RESULTS: Of 230 patients evaluated, 37% met criteria for Type D personality. Type D was associated with a decreased Mental Component score on the Short-Form Health Survey 12 (mean difference = -8.29; 95% confidence interval, 5.2-11.4; P < .001). On the Gastrointestinal Symptoms Severity Index, severity of symptoms was significantly higher in Type D patients compared with non Type D patients (P < .001). CONCLUSIONS: Type D personality was associated with decreased perceived HRQoL and reporting of more severe gastrointestinal symptoms. Type D personality construct may be an important consideration when assessing HRQoL outcomes. Consideration of personality traits could improve risk stratification in research and clinical practice in this patient group.

Emerging drugs for chronic constipation.

Chronic constipation (CC) is one of the most common functional gastrointestinal disorders. CC is estimated to affect up to 27% of the North American population. Although not life-threatening, CC can have profoundly negatively affects on quality of life and result in significant economic burden in terms of both direct and indirect healthcare costs. Possible etiologies for CC include alterations in gastrointestinal motility and secretion. Research efforts in CC have begun to identify multifactorial and often overlapping etiologies including abnormalities in myenteric neurons, alterations in neurotransmitters and their receptors, and incoordination of the muscles of the pelvic floor or anorectum. CC may be influenced by genetic predisposition, environmental factors and stress. In this article, the safety and efficacy of traditional and emerging therapies for CC are examined.

Impact of anal incontinence on psychosocial function and health-related quality of life.

The relationship among the frequency of anal incontinence (AI), psychosocial factors, and health-related quality of life (HRQOL) was evaluated. Consecutive patients (n=280) completed a bowel symptom questionnaire, the Symptom Checklist 90 -- Revised (SCL 90-R), and an assessment of HRQOL. Group 1 had no incontinence, Group 2 had AI less than once per week, and Group 3 experienced AI more than once per week. Multivariate analyses were used to evaluate the relationship among symptoms, the SCL-90-R subscales, and HRQOL. Group 3 reported more frequent stools than the other groups. Significant psychological distress was present in both incontinent groups compared to Group 1 (P=0.002). A reduction in overall HRQOL was also seen in the incontinent groups. Depression was inversely correlated with QOL-Satisfaction and QOL-Ratings and positively correlated with QOL-Interference. AI was associated with impaired psychosocial function and decreased HRQOL. The frequency of AI was associated with increased HRQOL-Interference, but minimally with the degree of psychosocial impairment.

Autoimmune gastrointestinal dysmotility treated successfully with pyridostigmine.

BACKGROUND & AIMS: Autoimmune gastrointestinal dysmotility (AGID) is a limited form of autoimmune autonomic neuropathy occurring idiopathically or in a paraneoplastic context. This disorder is considered rare, but is underrecognized as a cause for GI dysmotilities of varying anatomic extent, severity, and duration. We describe the diagnosis and management of an instructive case. METHODS: A 60-year-old (nondiabetic) woman presented with a 15-year history of severe isolated gastroparesis. Paraneoplastic autoantibody evaluation aided the diagnosis of AGID. This included indirect immunofluorescence (neuronal nuclear and cytoplasmic antibodies), radioimmunoprecipitation assays (neuronal and muscle plasma membrane cation channel antibodies), and enzyme-linked immunosorbent assay (muscle striational antibodies). RESULTS: Serologic testing revealed both ganglionic neuronal acetylcholine receptor and N-type voltage-gated calcium channel autoantibodies. This profile was consistent with AGID and, despite the long history, raised the possibility of lung, breast, or ovarian carcinoma or thymoma. An underlying neoplasm was excluded by appropriate investigations. In a 1-month trial of oral pyridostigmine therapy, the patient's GI symptoms improved and her weight stabilized. Pyridostigmine was continued at a low dose, and was supplemented by tegaserod. CONCLUSIONS: Autoimmune serology is a valuable adjunct to the diagnosis and guide to management of patients with AGID. The favorable response to acetylcholinesterase inhibitors, despite a 15-year history, suggests an immunopharmacologic rather than an inflammatory cytotoxic pathology. Immunomodulatory therapy may not always be required. Of numerous autoantibodies currently recognized as biomarkers of AGID, the ganglionic acetylcholine receptor autoantibody is the only proven pathophysiologic effector. Certain neuronal nuclear and cytoplasmic autoantibodies are highly predictive of an underlying malignancy.