Dietary fiber supplements: effects in obesity and metabolic syndrome and relationship to gastrointestinal functions.

Dietary fiber is a term that reflects a heterogeneous group of natural food sources, processed grains, and commercial supplements. Several forms of dietary fiber have been used as complementary or alternative agents in the management of manifestations of the metabolic syndrome, including obesity. Not surprisingly, there is a great variation in the biological efficacy of dietary fiber in the metabolic syndrome and body weight control. Diverse factors and mechanisms have been reported as mediators of the effects of dietary fiber on the metabolic syndrome and obesity. Among this array of mechanisms, the modulation of gastric sensorimotor influences appears to be crucial for the effects of dietary fiber but also quite variable. This report focuses on the role, mechanism of action, and benefits of different forms of fiber and supplements on obesity and the metabolic syndrome, glycemia, dyslipidemia, and cardiovascular risk and explores the effects of dietary fiber on gastric sensorimotor function and satiety in mediating these actions of dietary fiber.

Reproducibility and agreement of pharyngeal automated impedance manometry with videofluoroscopy.

BACKGROUND & AIMS: Automated impedance manometry analysis (AIM) measures swallow function variables that define bolus timing, intrabolus pressure, contractile vigor, and bolus presence; these are combined to derive a swallow risk index (SRI) that is correlated with pharyngeal dysfunction and aspiration. We assessed intra-rater and inter-rater reproducibility of AIM analysis-derived variables; the diagnostic accuracy of AIM-based criteria for detecting aspiration was determined by using expertly scored videofluoroscopy as the standard. METHODS: Data on 50 bolus swallows of 10 mL each were randomly selected from a database of swallows that were simultaneously recorded with impedance, manometry, and videofluoroscopy. Data were divided into 5 subgroups of 10 swallows for analysis: 10 dysphagic liquid, 10 dysphagic liquid with aspiration, 10 dysphagic semisolid, 10 control liquid, and 10 control semisolid. Repeat analyses were performed by 10 observers with varying levels of expertise in manometry by using purpose-designed software (AIMplot). Swallow videos were scored by 4 experts by using the penetration-aspiration scale (PAS) score. Reproducibility of calculation of swallow function variables and the SRI and PAS was assessed by using intraclass correlation coefficient (ICC). The majority consensus of expert PAS scores was used to dichotomously define aspiration (consensus PAS >3). Observer analyses were compared by Cohen κ statistical analysis. RESULTS: The intra-rater and inter-rater reproducibility of swallow function variables was high (SRI mean intra-rater ICC, 0.97 and mean inter-rater ICC, 0.91). SRI >15-20 was optimal for detecting the presence of aspiration during liquid bolus swallows with an almost perfect agreement with expert scoring of videofluoroscopy (κ > 0.8). CONCLUSIONS: AIM analysis has high intra-rater and inter-rater reproducibility, and among observers of varying expertise, SRI predicts the presence of aspiration.

Reproducibility and performance characteristics of colonic compliance, tone, and sensory tests in healthy humans.

BACKGROUND: The performance characteristics of colonic sensation and motility measurements are unclear. AIM: To compare left colon compliance, tone, and sensation in males and females and to evaluate inter and intra-individual coefficients of variation (COV) in these measurements. METHODS: Data were acquired using standard barostat methods, by one technologist, in 72 human volunteers (38 males, 18-65 years). We measured compliance, fasting tone, and sensation during baseline and post-placebo; postprandial (PP) tone was measured only post-placebo. Compliance and thresholds for first sensation, gas, and pain were measured using ascending method of limits; sensory ratings (0-100 mm VAS) using random phasic distensions at 8-36 mmHg above baseline operating pressure. Change in PP tone was measured by barostat balloon volume for the first 30 min after a 1000-kcal meal. Inter-COV was calculated as 100 (SD/mean), and intra-COV as (100 x SD delta/overall mean). RESULTS: There were no statistically significant associations with gender for most sensory or motor data at baseline. A modest association of fasting colonic tone and gender was observed. COV are lower (20-35%) for compliance, fasting tone, pain threshold, and sensation ratings than for PP tone and threshold for first or gas sensation (>45%). COV data are similar in males and females; sensation COVs appear smaller in females than in males. CONCLUSIONS: Testing of compliance, tone and pain, and gas sensation in left colon performs adequately to assess these functions in humans. Lower COV for sensation tests among females is relevant to plan studies of drugs intended for functional GI disorders.

Alterations in arterial blood parameters in patients with liver cirrhosis and ascites.

In cirrhotic patients, in addition to hepatocytes and Kuppfer cells dysfunction circulatory anatomic shunt and ventilation/perfusion (V(A)/ Q) ratio abnormalities can induce decrease in partial pressure of oxygen in arterial blood (PaO(2)), in oxygen saturation of hemoglobin (SaO(2)) as well as various acid-base disturbances. We studied 49 cases of liver cirrhosis (LC) with ascites compared to 50 normal controls. Causes were: posthepatic 37 (75.51%), alcoholic 7 (14.24%), cardiac 2 (4.08%), and cryptogenic 3 (6.12%). Complications were: upper gastrointestinal bleeding 24 (48.97), hepatic encephalopathy 20 (40.81%), gastritis 28 (57.14%), hepatoma 5 (10.2%), renal hepatic syndrome 2 (4.01%), HbsAg (+) 24 (48.97%), and hepatic pleural effusions 7 (14.28%). Average PaO(2) and SaO(2) were 75.2 mmHg and 94.5 mmHg, respectively, compared to 94.2 mmHg and 97.1 mmHg of the control group, respectively (p value in both PaO(2) and SaO(2 )was p<0.01). Respiratory alkalosis, metabolic alkalosis, metabolic acidosis, respiratory acidosis and metabolic acidosis with respiratory alkalosis were acid-base disturbances observed. In conclusion, portopulmonary shunt, intrapulmonary arteriovenous shunt and V(A)/Q inequality can induce a decrease in PaO(2) and SaO(2) as well as various acid-base disturbances. As a result, pulmonary resistance is impaired and patients more likely succumb to infections and adult respiratory distress syndrome.

Severity of fecal urgency and incontinence in inflammatory bowel disease: clinical, manometric and sonographic predictors.

BACKGROUND: Fecal incontinence (FI) and urgency are prevalent symptoms in patients with inflammatory bowel diseases (IBD). It is unclear which factors determine their severity. We evaluated associations of clinical activity, anorectal motility, and endoanal sonography with FI severity in IBD. METHODS: Fifty-eight consecutive IBD patients and 14 healthy volunteers participated in a cross-sectional, tertiary-center study. Active disease was defined as Crohn's disease activity index ≥ 150 and as simple clinical colitis index > 2. We assessed anal pressures and fatigue rate index (FRI) of the external anal sphincter (EAS) by manometry, rectal compliance and sensitivity by balloon distension, and sphincter defects by endoanal ultrasound. Significant bivariate associations between these parameters and the fecal incontinence severity scale (FISS) were evaluated in multivariate analysis. RESULTS: Twenty-seven patients (47%) reported urgency, 13 of which (22%) reported FI. Defects of the internal anal sphincter (IAS) and the EAS were diagnosed in 14 (24%) and 13 patients (22%), respectively. Patients had significantly lower rectal compliance and FRI compared with controls. FISS demonstrated significant bivariate associations with clinical disease activity (P = 0.0115), FRI (P = 0.0018), sonographic IAS and EAS defects (P < 0.0001 and 0.0059), rectal compliance (P = 0.0001), and volume at the threshold of a constant urge (Vurge, P = 0.0002). In multivariate analysis, FISS was associated with clinical disease activity (P = 0.0325), FRI (P = 0.0367), Vurge (P = 0.0091), and sonographic IAS defect(s) (P = 0.0008). The derived model explained 62% of the variance in FISS (P < 0.0001). CONCLUSIONS: Clinical disease activity and manometric and sonographic anorectal parameters are associated with FI severity in IBD. Prospective studies are warranted to evaluate their predictive value in continence outcomes.

Platelet IgG antibodies are significantly increased in chronic liver disease.

BACKGROUND: The aim of this study was to investigate the presence of IgG antiplatelet (anti-P) IgG antibodies in patients with chronic liver disease (CLD) of diverse but well defined etiology. METHODS: One-hundred fifty-six consecutive patients with CLD (65 with chronic hepatitis B, 57 with chronic hepatitis C, 23 with alcoholic liver disease and 11 with primary biliary cirrhosis), and 240 healthy blood donors were investigated for the presence of anti-P antibodies. RESULTS: Anti-P antibodies were present in 36.5% (57/156) of patients with CLD, and 2.9% (7/240) of controls (P=0.0001). In detail, anti-P antibodies were detected in 35.4% (23/65) of patients with chronic hepatitis B, 26.3% (15/57) of patients with chronic hepatitis C, 47.8% (11/23) of patients with alcoholic liver disease and 72.7% (8/11) of those with primary biliary cirrhosis. The study also demonstrated the significantly higher prevalence of anti-P antibodies in patients with cirrhosis (53.0%) than in non cirrhotic patients (26.4%, P=0.0018). The association of anti-P antibodies with thrombocytopenia was inconsistent. CONCLUSIONS: This study showed a high prevalence of anti-P IgG antibodies in patients with CLD compared to healthy controls.

Increased fatigability of external anal sphincter in inflammatory bowel disease: significance in fecal urgency and incontinence.

BACKGROUND AND AIMS: Fatigability of external anal sphincter (EAS) has not been studied in inflammatory bowel disease (IBD) patients. We evaluated EAS fatigability in IBD patients with and without fecal incontinence (FI) and urgency, and correlated fatigability with demographic and clinical factors, and EAS endosonography. METHODS: Fifty-eight consecutive IBD cases and 14 healthy volunteers completed Bristol stool form and a FI severity scale. Groups I, II and III included 27 patients with urgency including 13 with concomitant FI, 31 patients without FI or urgency, and 14 controls, respectively. We performed stationary pull-through manometry with an 8-channel water-perfused catheter. Fatigue rate (FR) was calculated by linear regression during a 20-s anal squeeze, and fatigue rate index (FRI) as the ratio of squeeze pressure increment to FR. EAS thickness and deficits were evaluated with an endoanal 10-MHz probe. Patients underwent sigmoidoscopy. RESULTS: Group I demonstrated a higher Bristol score, more frequent defecations, and more EAS defects compared to group II. Resting, peak squeeze pressures and EAS thickness did not differ between groups. FR was increased in group I versus II, and in group II versus III; FRI was decreased in group I versus II and in group II versus III (p<0.001, adjusting for age and BMI). Gender, oral glucocorticoids, presence of proctitis, perianal disease and EAS defects did not interact with group membership on FR or FRI. CONCLUSIONS: IBD is associated with increased fatigue rate and decreased fatigue rate index. These differences were even more striking in patients with incontinence or urgency.

A preliminary candidate genotype-intermediate phenotype study of satiation and gastric motor function in obesity.

Stomach motility contributes significantly to fullness sensation while eating and cessation of food intake in humans. Genes controlling adrenergic and serotonergic mechanisms (ADRA2A, GNB3, and SLC6A4) affect gastric emptying (GE), volume (GV), and satiation. Fat mass and obesity-associated gene (FTO) is linked with satiety. Our aim was to examine the association of these candidate genes with stomach functions that signal postprandial fullness: GE, GV, and maximum tolerated volume (MTV). These biomarkers constitute a component of the intermediate phenotype of satiation. A total of 62 overweight or obese participants underwent genotyping of the candidate genes, and validated measurements of GE of solids and liquids by scintigraphy, fasting and postprandial change in GV by SPECT (single photon emission computed tomography), and MTV by nutrient drink test. These markers of satiation were compared for 38 genetic variants in ADRA2A, ADR2C, ADRB3, uncoupling protein (UCP)-2 and -3, GNB3, FTO, and SLC6A4 using a recessive model of inheritance. ADRA2A, ADR2C, UCP-3, GNB3, and FTO loci were significantly associated with the intermediate phenotype markers of satiation: ADR2C (Ins-Del322_325) with accelerated GE; GNB3 (rs1047776) with delayed GE; ADRA2A (rs491589 and rs553668) and GNB3 (rs2269355, rs10849527, and rs3759348) with decreased postprandial GV; ADRA2A (rs3750625) and GNB3 (rs4963517 and rs1129649) with increased postprandial GV; UCP-3 (rs1685356) with increased MTV, and FTO (rs9939609) decreased MTV. Genetic susceptibility to postprandial satiation can be identified through intermediate phenotype markers. With independent validation, these markers may guide patient selection of weight-loss therapies directed at gastric motor functions.

Effect of alginate on satiation, appetite, gastric function, and selected gut satiety hormones in overweight and obesity.

Lack of control of food intake, excess size, and frequency of meals are critical to the development of obesity. The stomach signals satiation postprandially and may play an important role in control of calorie intake. Sodium alginate (based on brown seaweed Laminaria digitata) is currently marketed as a weight loss supplement, but its effects on gastric motor functions and satiation are unknown. We evaluated effects of 10 days treatment with alginate or placebo on gastric functions, satiation, appetite, and gut hormones associated with satiety in overweight or obese adults. We conducted a randomized, 1:1, placebo-controlled, allocation-concealed study in 48 overweight or obese participants with excluded psychiatric comorbidity and binge eating disorder. All underwent measurements of gastric emptying (GE), fasting, and postprandial gastric volumes (GVs), postprandial satiation, calorie intake at a free choice meal and selected gut hormones after 1 week of alginate (three capsules vs. matching placebo per day, ingested 30 min before the main meal). Six capsules were ingested with water 30 min before the GE, GV, and satiation tests on days 8-10. There were no treatment group effects on GE or volumes, gut hormones (ghrelin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), peptide YY (PYY)), satiation, total and macronutrient calorie intake at a free choice meal. There was no difference detected in results between obese and overweight patients. Alginate treatment for a period of 10 days showed no effect on gastric motor functions, satiation, appetite, or gut hormones. These results question the use of short-term alginate treatment for weight loss.

Actions and therapeutic pathways of ghrelin for gastrointestinal disorders.

Ghrelin is a peptide hormone that possesses unique orexigenic properties. By acting on the growth-hormone secretagogue receptor 1a, ghrelin induces a short-term increase in food consumption, which ultimately induces a positive energy balance and increases fat deposition. Reduced ghrelin levels have been observed in obese patients and after bariatric surgery. In particular, bariatric procedures that involve gastric resection or bypass lead to reduced ghrelin levels. Administration of physiological doses of exogenous ghrelin to humans does not significantly alter gastric motility; however, administration of high doses stimulates gastric motility, with increased gastric tone and emptying, and increased activity of migrating motor complexes in the small bowel. The potential of ghrelin agonists to be used as prokinetics is being tested in patients with gastroparesis and postoperative ileus. Ghrelin acts directly on pancreatic islet cells to reduce insulin production. Findings from studies in animals have revealed that small-molecule ghrelin antagonists favorably influence glucose tolerance, appetite suppression and weight loss. Other studies have demonstrated that ghrelin antagonists retard gastric emptying only at very high doses, which suggests that these agents will probably not induce upper gastrointestinal symptoms. The potential of this new class of therapeutic agents to influence appetite and glycemic control strongly indicates that they should be tested in clinical trials.

Effect of a chloride channel activator, lubiprostone, on colonic sensory and motor functions in healthy subjects.

Lubiprostone, a bicyclic fatty acid chloride channel activator, is efficacious in treatment of chronic constipation and constipation-predominant irritable bowel syndrome. The study aim was to compare effects of lubiprostone and placebo on colonic sensory and motor functions in humans. In double-blind, randomized fashion, 60 healthy adults received three oral doses of placebo or 24 microg lubiprostone per day in a parallel-group, placebo-controlled trial. A barostat-manometry tube was placed in the left colon by flexible sigmoidoscopy and fluoroscopy. We measured treatment effects on colonic sensation and motility with validated methods, with the following end points: colonic compliance, fasting and postprandial tone and motility indexes, pain thresholds, and sensory ratings to distensions. Among participants receiving lubiprostone or placebo, 26 of 30 and 28 of 30, respectively, completed the study. There were no overall effects of lubiprostone on compliance, fasting tone, motility indexes, or sensation. However, there was a treatment-by-sex interaction effect for compliance (P = 0.02), with lubiprostone inducing decreased fasting compliance in women (P = 0.06) and an overall decreased colonic tone contraction after a standard meal relative to fasting tone (P = 0.014), with greater effect in women (P < 0.01). Numerical differences of first sensation and pain thresholds (P = 0.11 in women) in the two groups were not significant. We concluded that oral lubiprostone 24 microg does not increase colonic motor function. The findings of decreased colonic compliance and decreased postprandial colonic tone in women suggest that motor effects are unlikely to cause accelerated colonic transit with lubiprostone, although they may facilitate laxation. Effects of lubiprostone on sensitivity deserve further study.

An unusual case of Crohn's disease with unresponsive pleural exudates. Is Crohn's disease finally a systemic immunological disorder?

Crohn's disease has been infrequently associated with various respiratory manifestations. Reports of pleural effusions in Crohn's disease are even sparser, but differential diagnosis is rich, with causes either associated with the disease or being independent. Processes directly or indirectly related to therapy, entities overlapping with Crohn's disease in pathogenesis and common causes of effusions should all be considered, under the guidance of laboratory testing and imaging. We report here an unusual case of bilateral pleural effusions unresponsive so far to medical therapy, in a patient with long-standing Crohn's disease and several features of autoimmunity. A short review of the literature is presented, the differential diagnosis is outlined and the systemic immunological profile of Crohn's disease is discussed.