Impact of bread diet on intestinal dysbiosis and irritable bowel syndrome symptoms in quiescent ulcerative colitis: A pilot study.

Gut microbiota may be involved in the presence of irritable bowel syndrome (IBS)-like symptomatology in ulcerative colitis (UC) patients in remission. Bread is an important source of dietary fiber, and a potential prebiotic. To assess the effect of a bread baked using traditional elaboration, in comparison with using modern elaboration procedures, in changing the gut microbiota and relieving IBS-like symptoms in patients with quiescent ulcerative colitis. Thirty-one UC patients in remission with IBS-like symptoms were randomly assigned to a dietary intervention with 200 g/d of either treatment or control bread for 8 weeks. Clinical symptomatology was tested using questionnaires and inflammatory parameters. Changes in fecal microbiota composition were assessed by high-throughput sequencing of the 16S rRNA gene. A decrease in IBS-like symptomatology was observed after both the treatment and control bread interventions as reductions in IBS-Symptom Severity Score values (p-value < 0.001) and presence of abdominal pain (p-value < 0.001). The treatment bread suggestively reduced the Firmicutes/Bacteroidetes ratio (p-value = 0.058). In addition, the Firmicutes/Bacteroidetes ratio seemed to be associated with improving IBS-like symptoms as suggested by a slight decrease in patient without abdominal pain (p-value = 0.059). No statistically significant differential abundances were found at any taxonomic level. The intake of a bread baked using traditional elaboration decreased the Firmicutes/Bacteroidetes ratio, which seemed to be associated with improving IBS-like symptoms in quiescent ulcerative colitis patients. These findings suggest that the traditional bread elaboration has a potential prebiotic effect improving gut health (ClinicalTrials.gov ID number of study: NCT05656391).

Characteristics of Patients with Crohn's Disease With or Without Perianal Fistulae in the CorEvitas Inflammatory Bowel Disease Registry.

BACKGROUND: There are limited real-world data characterizing perianal fistulae in patients with Crohn's disease (CD). AIM: To describe characteristics of patients with CD with and without perianal fistulae. METHODS: In this cross-sectional study, characteristics, treatment history, and health outcomes of patients with CD enrolled in the CorEvitas IBD Registry were described according to perianal fistula status (current/previous or none). RESULTS: Eight hundred and seventy-eight patients were included. Compared with patients with no perianal fistulae (n = 723), patients with current/previous perianal fistulae (n = 155) had longer disease duration since CD diagnosis (mean 16.5 vs 12.3 years; difference 4.3 years; 95% CI, 2.0, 6.6) and fewer had Harvey-Bradshaw Index scores indicative of remission (0-4, 56.8% vs 69.6%; difference - 12.9%; 95% CI, - 21.6, - 4.2). More patients with current/previous fistulae reported a history of IBD-related emergency room visits (67.7% vs 56.1%; difference 11.6%; 95% CI, 3.4, 19.8), hospitalizations (76.1% vs 58.4%; difference 17.7%; 95% CI, 10.1, 25.4), and surgeries (59.4% vs 27.7%; difference 31.7%; 95% CI, 23.3, 40.1), and a history of treatment with tumor necrosis factor inhibitors (81.3% vs 60.7%; difference 20.6%; 95% CI, 13.5, 27.7), immunosuppressants (51.6% vs 31.2%; difference 20.4%; 95% CI, 11.9, 29.0), and antibiotics (50.3% vs 23.7%; difference 26.6%; 95% CI, 18.2, 35.1) than patients without perianal fistulae. CONCLUSIONS: Patients with CD with current/previous perianal fistulae have more symptomatic experiences of disease, higher medication use, hospitalization rates, and emergency room visits than patients without perianal fistulae. Interventions to prevent/reduce risk of developing fistulae may help improve outcomes in CD.

In vitro Prebiotic Effect of Bread-Making Process in Inflammatory Bowel Disease Microbiome.

Inflammatory bowel disease (IBD), including its two main categories (Crohn's disease and ulcerative colitis), has been linked both to gut microbiota and to diet. Bread is a daily food that has a potential capacity as a prebiotic. Our aim was to evaluate different bread-making processes and their effect on fecal colonic microbiota in IBD patients. The microbial composition of several sourdoughs and dough samples was analyzed by high-throughput sequencing of 16S and 18S rRNA genes. Three types of bread, which followed different bread-making processes, were in vitro digested and incubated with feces from IBD patients. Changes in gut microbiota were assessed by a quantitative polymerase chain reaction using specific bacterial sequence targets. Short-chain fatty acid production was also analyzed by gas chromatography. Lactobacillus sanfranciscensis was the dominant lactic acid bacteria species found in sourdough and bread doughs prepared using sourdough, whereas Saccharomyces cerevisiae was the most dominant yeast in all groups, especially in bread doughs before baking. Differences in microbial composition in raw bread doughs were more related to the type of dough and elaboration than to fermentation time lengths. The analysis of in vitro fecal incubations with bread conditions revealed an increase in most bacterial groups analyzed and short-chain fatty acid production, both in Crohn's disease and ulcerative colitis samples. Most remarkable increases in short-chain fatty acid production mirrored higher abundances of Roseburia species. The potential prebiotic properties observed were mainly obtained when using a high quantity of bread, regardless of bread type. Overall, this study highlights the bacterial dynamics within the bread-making process and the potential prebiotic effect in IBD patients.

Clinical response to linaclotide at week 4 predicts sustained response in irritable bowel syndrome with constipation and improvements in digestive and extra-digestive symptoms.

BACKGROUND: Linaclotide is approved for the treatment of moderate-to-severe irritable bowel syndrome (IBS) with constipation (IBS-C) in adults. This study aimed to assess factors predictive of a clinical response and improvements in non-IBS symptoms with linaclotide treatment in a Spanish patient population. METHODS: In this open-label phase IIIb study, patients with moderate-to-severe IBS-C received linaclotide 290 µg once daily for 12 weeks. The primary endpoint was clinical response at week 12, defined as >30% reduction in IBS symptom severity score (IBS-SSS) or IBS-SSS <75 plus self-reported response of feeling 'better' or 'much better' versus the baseline. Digestive nonintestinal and extra-digestive symptom scores were assessed. Baseline characteristics and week 4 clinical response were assessed as predictors of week 12 clinical response. RESULTS: A total of 96 patients were eligible; 91 were female and the mean age was 47.4 years. Mean (SD) baseline IBS-SSS was 371 (72.5). In the intention-to-treat and per-protocol populations, 22.9% and 31.7% were clinical responders at week 4, respectively, and 25.0% and 36.7% were clinical responders at week 12. Digestive nonintestinal and extra-digestive symptom scores were significantly improved at weeks 4 and 12. Baseline characteristic was not associated with week 12 clinical response; however, clinical response at week 4 was predictive of response at week 12 (OR: 6.5; 95%IC: 2.1-19.8). The most common adverse event was diarrhea inclusive of loose or watery stools (35.4%). CONCLUSIONS: Linaclotide improves IBS-C symptoms, including digestive nonintestinal and extra-digestive symptoms. A clinical response at week 4 may predict response at week 12.

Optimizing the Use of Linaclotide in Patients with Constipation-Predominant Irritable Bowel Syndrome: An Expert Consensus Report.

INTRODUCTION: Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by chronic or recurrent abdominal pain in association with defecation or a change in bowel habits. A predominant disorder of bowel habits, IBS is classified into three main subtypes: constipation-predominant IBS (IBS-C), diarrhea-predominant IBS (IBS-D) and IBS alternating between constipation and diarrhea (IBS-M). Linaclotide is a first-in-class, oral, once-daily guanylate cyclase-C receptor agonist (GC-CA) that is licensed for the symptomatic treatment of moderate-to-severe IBS-C in adults. This review aims to facilitate and optimize clinical practices, establishing common guidelines to monitor patients with IBS-C that are treated with linaclotide. METHODS: A group of experts in functional digestive disorders was convened to review the efficacy and safety of linaclotide and to develop an updated consensus report for the treatment of patients with IBS-C. A search was performed for English, French and Spanish language articles in PubMed. On the basis of the articles identified, an initial document was drafted addressing different issues frequently raised by general practitioners and GI specialists that are related to the prescription, efficacy and safety of linaclotide. This document was then reviewed and modified by the expert panel until a final text was agreed upon and validated. RESULTS: Based on the evidence, the panel addressed the following recommendations: (1) Linaclotide is indicated for the treatment of moderate to severe IBS-C in adults; (2) it is recommended that patients take linaclotide continuously and not sporadically; (3) patients should be warned about the risk of diarrhea and given choices concerning how to deal with this possible side effect; (4) the absence of tachyphylaxis or potential risks implies that linaclotide treatment can be maintained for long periods of time. CONCLUSIONS: This document seeks to lay down a set of recommendations and to identify key issues that may be useful for the clinical management of IBS-C patients treated with linaclotide.

Clinical practice guidelines for the management of constipation in adults. Part 1: Definition, aetiology and clinical manifestations. / Guía de práctica clínica sobre el manejo del estreñimiento crónico en el paciente adulto. Parte 1: Definición, etiología y manifestaciones clínicas.

Clinical practice guidelines for the management of constipation in adults aim to generate recommendations on the optimal approach to chronic constipation in the primary care and specialized outpatient setting. Their main objective is to provide healthcare professionals who care for patients with chronic constipation with a tool that allows them to make the best decisions about the prevention, diagnosis and treatment of this condition. They are intended for family physicians, primary care and specialist nurses, gastroenterologists and other health professionals involved in the treatment of these patients, as well as patients themselves. The guidelines have been developed in response to the high prevalence of chronic constipation, its impact on patient quality of life and recent advances in pharmacological management. The Grading of Recommendations Assessment, Development and Evaluation Working Group (GRADE) system has been used to classify the scientific evidence and strengthen the recommendations.

Practical aspects of high resolution esophageal manometry.

High resolution esophageal manometry (HRM) is currently under development as can be seen in the various Chicago classifications. In order to standardize criteria in certain practical aspects with limited scientific evidence, the First National Meeting for Consensus in High Resolution Manometry of the Spanish Digestive Motility Group took place, bringing together a wide group of experts. The proposals were based on a prior survey composed of 47 questions, an exhaustive review of the available literature and the experience of the participants. Methodological aspects relating to the poorly defined analysis criteria of certain new high resolution parameters were discussed, as well as other issues previously overlooked such as spontaneous activity or secondary waves. Final conclusions were drawn with practical applications.

Caloric intake capacity as measured by a standard nutrient drink test helps to predict weight loss after bariatric surgery.

BACKGROUND: Instruments that enable to select individuals that will benefit most from bariatric surgery (BS) are necessary to increase its cost-efficiency. Our goal was to assess if intake capacity, measured with a standardized test, predicts response to BS. METHODS: Patients with criteria for BS were randomly allocated to laparoscopic gastric bypass (LRYGB) or sleeve gastrectomy (LSG). We measured caloric intake capacity before and 1 year after surgery using a standardized nutrient drink test. We evaluated if pre-surgery satiation could predict satiation and weight loss (%) 1 year after surgery using multiple regression modeling. Descriptive statistics are given as mean ± SD. RESULTS: Fourteen women (48 ± 9 years old, BMI 41 ± 3 kg/m(2)) were evaluated before and 11 ± 2.6 months after surgery (seven LRYGB, seven LSG). Caloric intake capacity diminished after surgery (-950 ± 85 kcal on average [70 ± 8 % decrease over basal intake capacity]; p=0.002) and similarly in both LRYGB (72 ± 7 % decrease) and LSG groups (68 ± 8 % decrease); p=0.5. There was a significant weight reduction after surgery (-32 ± 10 kg [30 ± 8 % of total basal weight]) with a mean post-surgery BMI of 29 ± 2 kg/m(2). The best predictive model of weight loss (%) after surgery (R (2)=89 %, p=0.0009) included: BMI (p=0.0004), surgery type (p=0.01) and pre-surgery intake capacity (p=0.006). Weight loss was higher in heavier patients and those undergoing LRYGB. Patients with higher intake capacity had a poorer outcome independently of basal BMI and surgery type. CONCLUSIONS: Caloric intake capacity, as measured by a standard nutrient drink test, helps to predict weight loss after bariatric surgery. This test might be useful in algorithms of obesity treatment decision.

Outcome in obscure gastrointestinal bleeding after capsule endoscopy.

AIM: To investigate the clinical impact of capsule endoscopy (CE) after an obscure gastrointestinal bleeding (OGIB) episode, focusing on diagnostic work-up, follow-up and predictive factors of rebleeding. METHODS: Patients who were referred to Hospital del Mar (Barcelona, Spain) between 2007 and 2009 for OGIB who underwent a CE were retrospectively analyzed. Demographic data, current treatment with non-steroid anti-inflammtory drugs or anticoagulant drugs, hemoglobin levels, transfusion requirements, previous diagnostic tests for the bleeding episode, as well as CE findings (significant or non-significant), work-up and patient outcomes were analyzed from electronic charts. Variables were compared by χ (2) analysis and Student t test. Risk factors of rebleeding were assessed by Log-rank test, Kaplan-Meier curves and Cox regression model. RESULTS: There were 105 patients [45.7% women, median age of 72 years old (interquartile range 56-79)] and a median follow-up of 326 d (interquartile range 123-641) included in this study. The overall diagnostic yield of CE was 58.1% (55.2% and 63.2%, for patients with occult OGIB and overt OGIB, respectively). In 73 patients (69.5%), OGIB was resolved. Multivariate analysis showed that hemoglobin levels lower than 8 g/dL at diagnosis [hazard ratios (HR) = 2.7, 95%CI: 1.9-6.3], patients aged 70 years and above (HR = 2.1, 95%CI: 1.2-6.1) and significant findings in CE (HR = 2.4, 95%CI: 1.1-5.8) were independent predictors of rebleeding. CONCLUSION: One third of the patients presented with rebleeding after CE; risk factors were hemoglobin levels < 8 g/dL, age ≥ 70 years or the presence of significant lesions.

[Endoanal ultrasound findings in patients with faecal incontinence using a scoring system]. / Descripción de los hallazgos de la ecografía endoanal en pacientes con incontinencia fecal mediante un sistema de puntuación.

INTRODUCTION: The main aim of the study was to apply a severity classification of sphincter lesions detected by endoanal ultrasound using Starck score in patients who suffered faecal incontinence. MATERIAL AND METHOD: Data were analysed on 133 patients with faecal incontinence. Those in whom anal sphincter lesions were detected by endoanal ultrasound are described and their corresponding scores according to Starck classification calculated. This system scores severity of detected sphincter lesions from 0 to 16, involving the three axes of the anal canal. Patient demographic characteristics and anorectal manometry results were also analysed. The relationship between this score, patient gender and age, and anorectal manometric results were also analysed. RESULTS: A total of 83 (62.4%) patients had some type of anal sphincter lesion. The presence of sphincter defects was not related to gender (P=0.172), although it did correlate with younger ages (P=0.028). The severity of anal sphincter damage by Starck score did not show significant correlation to gender (P=0.327) or to the age (P=0.350) of patients. However, a significant correlation was detected between Starck score and anal resting pressure (P=0.008) or anorectal squeeze pressure (P=0.011). CONCLUSIONS: The presence of anal sphincter injuries could be well defined by Starck score in patients with faecal incontinence. Severity of damage scored by Starck correlated with anorectal manometric results.

[Results of national survey of specialists on the clinical evaluation of faecal incontinence]. / Resultados de una encuesta nacional dirigida a especialistas sobre la evaluación clínica de pacientes con incontinencia fecal.

INTRODUCTION: Faecal incontinence is a high prevalence disease in the general population. The aims of this study were to analyse which severity grading systems of faecal incontinence are used in Spain and to find out if there are differences in their use among specialists who manage these patients. MATERIAL AND METHODS: A postal questionnaire survey was sent to all hospitals of the National Health Service in Spain in order to study the attitudes and opinions of general surgery and gastroenterology specialists regarding the clinical evaluation of patients with faecal incontinence. RESULTS: Ninety-nine questionnaires were returned fully completed (65 surgeons and 34 gastroenterologists). Only 41.8% of responders used a diary card systematically (46.8% surgeons vs. 32.3% gastroenterologists; p = 0.05). The Wexner score is the most widely grading system used in clinical practice (85.8% surgeons vs. 50% gastroenterologists; p = 0.01). The most relevant issues in the evaluation of these patients were considered: Type of faecal incontinence, frequency of leakage and quality of life. Finally, 85.5% of those questioned said that the universal acceptance of severity grading systems by all specialists would be an improvement, and 98.9% considered it useful to start a national plan of information regarding clinical evaluation of faecal incontinence in Spain. CONCLUSIONS: There is variability in how faecal incontinence is evaluated among specialists in Spain.

High body mass alters colonic sensory-motor function and transit in humans.

There is increased prevalence of abdominal pain and diarrhea and decreased gastric sensation with increased body mass index (BMI). Our hypothesis is that increased BMI is associated with increased colonic motility and sensation. The study aim was to assess effect of BMI on colonic sensory and motor functions and transit. We used a database of colonic tone, compliance, and perception of distensions measured by intracolonic, barostat-controlled balloon, and gastrointestinal transit was measured by validated scintigraphy in healthy obese and nonobese subjects. Regression analysis was applied to assess the association of BMI with colonic sensory and motor functions. We included adjustments for sex differences, age, height, balloon volumes during distension, and psychological stress. Among 165 participants (87 women, 78 men), increased BMI was associated with decreased colonic compliance (P < 0.006, adjusted), decreased pain rating during distensions (P = 0.02, adjusted), and a higher threshold for pain (P = 0.042, adjusted). Sensation for gas, colonic tone, and contraction after meal ingestion were not significantly associated with BMI. Transit was assessed in 72 participants (41 women, 31 men); colonic transit was faster with BMI >30 kg/m(2) (P = 0.003 unadjusted, P = 0.08 adjusted for gender). In conclusion, BMI >25 kg/m(2) is associated with decreased colonic compliance and pain sensation; colonic transit is accelerated particularly with BMI >30 kg/m(2) in women. These data suggest that colonic dysfunction may contribute to diarrhea, but the cause of increased abdominal pain in obesity is not explained by the studies of colonic sensation and requires further study of afferent, spinal, and central mechanisms.

Effect of gastric volume or emptying on meal-related symptoms after liquid nutrients in obesity: a pharmacologic study.

BACKGROUND & AIMS: Altered postprandial satiation influences food intake in obesity. The aim of this study was to evaluate the contribution of gastric motor functions to intra- and postprandial symptoms in obese, otherwise healthy, people. METHODS: In a randomized, parallel-group, double-blind design, 40 obese (body mass index>30 kg/m2) healthy volunteers (n=10/group) received intravenous saline (placebo), atropine (.02 mg/kg), or erythromycin (1 or 3 mg/kg) to alter gastric volume and emptying after liquid nutrient meals, measured by validated imaging methods. The nutrient drink test assessed the volume ingested at maximum satiation, and intra- and early postprandial symptoms. Relationships between gastric motor functions, meal size, and symptoms were assessed by using multiple regression. Circulating levels of candidate upper-gut hormones involved in satiation were measured. RESULTS: Relative to placebo, atropine retarded gastric emptying and increased gastric volumes; erythromycin accelerated gastric emptying and reduced gastric volumes during fasting. Although similar maximal tolerated volumes were recorded across treatments, intra- and immediate postprandial symptoms were increased by these perturbations, particularly nausea and bloating. Upper-gut hormonal profiles generally reflected changes in gastric emptying. Regression analysis showed that fasting predrug gastric volume was a significant predictor of intra- and postprandial bloating. Change in gastric volume postdrug or postmeal did not contribute additionally to predicting intra- or postprandial symptoms. There was significant (negative) association between gastric emptying and fullness score, and significant (positive) association with hunger score 30 minutes postprandially. CONCLUSIONS: In obese individuals, fasting gastric volumes and gastric emptying, but not postprandial gastric volumes, were associated with intra- and postprandial symptoms. Understanding the determinants of gastric volume may provide insights on mechanisms controlling satiation.

Visceral hypersensitivity.

Visceral hypersensitivity is considered one of the causes of functional gastrointestinal disorders. The objectives of this review are to provide a practical description of neuroanatomy and physiology of gut sensation, to describe the diverse tests of visceral sensation and the potential role of brain imaging to further our understanding of visceral sensitivity in health and disease. Changes in motor function in the gut may influence sensory levels, eg, during contractions or as a result of changes in viscus compliance. New insights on sensory end organs, such as intraganglionic laminar endings, and basic neurophysiologic studies showing afferent firing during changes in stretch rather than tension illustrate the importance of different types of stimuli, not just tension, to stimulate afferent sensation. These insights provide the basis for understanding visceral sensation in health and disease, which will be extensively discussed in subsequent articles.

Contributions of gastric volumes and gastric emptying to meal size and postmeal symptoms in functional dyspepsia.

BACKGROUND & AIMS: The aim was to assess relative contributions of gastric volumes (GV) and gastric emptying (GE) to meal size and postprandial symptoms in patients with functional dyspepsia. METHODS: Patients with chronic upper gastrointestinal symptoms were prospectively evaluated. GV during fasting and after 300 mL Ensure was measured with 99m Tc-single-photon emission computed tomography imaging and solid GE (99m Tc-egg) by scintigraphy. Maximum tolerated volume (MTV) and symptoms were measured after Ensure challenge. RESULTS: Of 57 adult patients evaluated, 39 (23 women, 16 men) met Rome II criteria for functional dyspepsia and had no other diagnosis to account for dyspepsia. The most frequent symptoms were abdominal pain (90%), pain predominantly after meals (76%), nausea (85%), and early fullness after meals (79%). Relative to established laboratory normal values, MTV was abnormal in 82%, aggregate symptom score >209 in 72%, GE (at 1 hour) accelerated in 41%, GE (at 4 hours) delayed in 41%, and postmeal GV reduced in 52%. Lower body mass was associated with lower MTV and higher postchallenge symptoms. Lower fasting (not postprandial) GV and faster GE were independent predictors of lower MTV, explaining 18% of the variance after adjusting for body weight (32% of variance). GE was an independent predictor of postchallenge symptoms (10% of variance) after adjusting for volume ingested (10%), age (20%), and weight (10%). CONCLUSIONS: In adults with functional dyspepsia seen in a tertiary referral practice, decreased meal size and postmeal symptoms are associated with low fasting GV and faster GE. These data provide physiologic targets for ameliorating symptoms of functional dyspepsia.

Obesity is associated with increased risk of gastrointestinal symptoms: a population-based study.

OBJECTIVES: Perception of sensations arising from the gastrointestinal tract may be diminished in obese subjects and thus facilitate overeating. Alternatively, excess food intake may cause gastrointestinal (GI) symptoms in obese patients. We evaluated the relationship between body mass index (BMI) and specific GI symptoms in the community. METHODS: Residents of Olmsted County, MN were selected at random to receive by mail one of two validated questionnaires. The association of reported GI symptoms with BMI (kg/m(2)) was assessed using a logistic regression analysis adjusting for age, gender, psychosomatic symptom score, and alcohol and tobacco use. RESULTS: Response rate was 74% (1,963 of 2,660). The prevalence of obesity (BMI > or = 30 kg/m(2)) was 23%. There was a positive relationship between BMI and frequent vomiting (p= 0.02), upper abdominal pain (p= 0.03), bloating (p= 0.002), and diarrhea (p= 0.01). The prevalence of frequent lower abdominal pain, nausea, and constipation was increased among obese (BMI > or = 30 kg/m(2)) compared to normal weight participants, however, no significant association was found between BMI and these symptoms. CONCLUSIONS: In the community, increasing BMI is associated with increased upper GI symptoms, bloating, and diarrhea. Clarification of the cause-and-effect relationships and the mechanisms of these associations require further investigation.

The role of pelvic floor dysfunction and slow colonic transit in adolescents with refractory constipation.

OBJECTIVE: Although pelvic floor dysfunction (PFD) is recognized as a cause of refractory constipation in adults, this diagnosis is not frequently considered in children and adolescents with refractory constipation. The purpose of this study was to examine the symptoms and colonic transit in adolescents with constipation evaluated for a disorder in pelvic floor function. METHODS: Adolescents with refractory constipation who had undergone anorectal manometry (ARM) and balloon expulsion test (BET) were identified by retrospective review of records. Initial symptoms and the clinician's assessment were used to categorize patients by pediatric Rome II criteria, that is, functional constipation (FC), constipation-predominant irritable bowel syndrome (C-IBS) or functional fecal retention (FFR). Results of scintigraphic colonic transit studies were evaluated. A chi2 test was used to assess the association between individual clinical symptoms and Rome II criteria. RESULTS: Sixty-seven adolescents underwent evaluation of pelvic floor function by tests for PFD: BET was abnormal in 42%. There was no underlying disease or alternative diagnosis to account for the constipation in these patients. Among the 41 patients who also underwent scintigraphic colonic transit, 30% had slow transit constipation and 12% had both slow colonic transit and abnormal BET. Patients classified as C-IBS were more likely to report weight loss (p = 0.03), bloating (p = 0.04), and incomplete rectal evacuation (p = 0.03). CONCLUSION: Abnormal pelvic floor function and delayed colonic transit are demonstrable as single or combined problems in adolescents with refractory constipation.

Functional dyspepsia: drugs for new (and old) therapeutic targets.

The therapeutic management of functional dyspepsia remains a major challenge for the gastroenterologist. Current therapies available are based on putative underlying pathophysiologic mechanisms, including gastric acid sensitivity, slow gastric emptying and Helicobacter pylori infection, but only a small proportion of patients achieve symptomatic benefit from these therapeutic approaches. Relatively novel mechanistic concepts under testing include impaired gastric accomodation, visceral hypersensitivity, and central nervous system dysfunction. Serotonergic modulators (e.g. the 5-HT4 agonist tegaserod, the 5-HT3 antagonist alosetron and the 5-HT1P agonist sumatriptan), CCK-1 antagonists (e.g. dexloxiglumide), opioid agonists (e.g. asimadoline), N-methyl-D-aspartate (NMDA) receptor antagonists (e.g dextromethorphan), neurokinin antagonists (e.g. talnetant), capsaicin-like agents and antidepressants are among the agents currently under investigation. It seems unlikely, however, that targeting a single mechanism with an individual drug will result in complete symptom remission in most cases.

Effect of oral CCK-1 agonist GI181771X on fasting and postprandial gastric functions in healthy volunteers.

CCK influences satiation and gastric and gallbladder emptying. GI181771X is a novel oral CCK-1 agonist; its effects on gastric emptying of solids, accommodation, and postprandial symptoms are unclear. Effects of four dose levels of the oral CCK-1 agonist GI181771X and placebo on gastric functions and postprandial symptoms were compared in 61 healthy men and women in a randomized, gender-stratified, double-blind, double-dummy placebo-controlled, parallel group study. Effects of 0.1, 0.5, and 1.5 mg of oral solution and a 5.0-mg tablet of GI181771X on gastric emptying of solids by scintigraphy, gastric volume by (99m)Tc-single photon emission computed tomographic imaging, maximum tolerated volume of Ensure, and postprandial nausea, bloating, fullness, and pain were studied. On each of 3 study days, participants received their randomly assigned treatment. Adverse effects and safety were monitored. There were overall group effects of GI181771X on gastric emptying (P < 0.01) and fasting and postprandial volumes (P = 0.036 and 0.015, respectively). The 1.5-mg oral solution of GI181771X significantly delayed gastric emptying of solids (P < 0.01) and increased fasting (P = 0.035) gastric volumes without altering postprandial (P = 0.056) gastric volumes or postprandial symptoms relative to placebo. The effect of the 5.0-mg tablet on gastric emptying of solids did not reach significance (P = 0.052). Pharmacokinetic profiles showed the highest area under the curve over 4 h for the 1.5-mg solution and a similar area under the curve for the 0.5-mg solution and 5-mg tablet. Adverse effects were predominantly gastrointestinal and occurred in a minority of participants. GI181771X delays gastric emptying of solids and exhibits an acceptable safety profile in healthy participants. CCK-1 receptors can be modulated to increase fasting gastric volume.