Gastric accommodation in healthy subjects studied by ultrasound, manometry, and impedancemetry.

BACKGROUND: Gastric accommodation to a meal may be important in the pathogenesis of upper gastrointestinal disorders, but has been difficult to investigate in a minimally invasive fashion. METHODS: We studied gastric and lower esophageal physiology during food intake, combining transabdominal ultrasound, multichannel high-resolution impedance-manometry (HRIM) and a symptom questionnaire. A HRIM catheter was distally positioned at incisura angularis and 300 mL saline with 75 g glucose was ingested. Target variables were recorded for 30 min after fluid intake. KEY RESULTS: Fifteen healthy subjects' participated (11W/4M, median age 23.8 y) and all accepted the meal with few symptoms. At incisura angularis maximum change in pressure from pre-intake values was -7.4 mmHg after 60 s (P < .0001), rising to pre-intake values within 20 min. The corresponding area increased significantly from pre-intake values of 8.0 cm2 to 14.1 cm2 shortly after intake (P = .0012), peaked at 5 min and slowly decreased towards 30 min. The corresponding maximum change in stress from pre-intake pressure values was -59.2 mmHg shortly after (P < .0001), reaching pre-intake values within 20 min. Strain rose from 0 shortly before to 0.36 shortly after (P < .0001), peaking at 5 min. At incisura angularis, fullness was positively correlated with area and to strain, while fullness, area, and stress were negatively correlated with pressure. CONCLUSIONS & INFERENCES: The multimodal method enabled assessment of the gastric accommodation reflex, stress and strain in the stomach. It triggered few symptoms in healthy volunteers. We propose it to be a more physiological replacement of the barostat technique.

Effects of varying dietary content of fermentable short-chain carbohydrates on symptoms, fecal microenvironment, and cytokine profiles in patients with irritable bowel syndrome.

BACKGROUND: A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) is increasingly recommended for patients with irritable bowel syndrome (IBS). We aimed to investigate the effects of a blinded low-FODMAP vs high-fructo-oligosaccharides (FOS) diet on symptoms, immune activation, gut microbiota composition, and short-chain fatty acids (SCFAs). METHODS: Twenty patients with diarrhea-predominant or mixed IBS were instructed to follow a low-FODMAP diet (LFD) throughout a 9-week study period. After 3 weeks, they were randomized and double-blindly assigned to receive a supplement of either FOS (FODMAP) or maltodextrin (placebo) for the next 10 days, followed by a 3-week washout period before crossover. Irritable bowel syndrome severity scoring system (IBS-SSS) was used to evaluate symptoms. Cytokines (interleukin [IL]-6, IL-8, and tumor necrosis factor alpha) were analyzed in blood samples, and gut microbiota composition (16S rRNA) and SCFAs were analyzed in fecal samples. KEY RESULTS: Irritable bowel syndrome symptoms consistently improved after 3 weeks of LFD, and significantly more participants reported symptom relief in response to placebo (80%) than FOS (30%). Serum levels of proinflammatory IL-6 and IL-8, as well as levels of fecal bacteria (Actinobacteria, Bifidobacterium, and Faecalibacterium prausnitzii), total SCFAs, and n-butyric acid, decreased significantly on the LFD as compared to baseline. Ten days of FOS supplementation increased the level of these bacteria, whereas levels of cytokines and SCFAs remained unchanged. CONCLUSIONS AND INFERENCES: Our findings support the efficacy of a LFD in alleviating IBS symptoms, and show changes in inflammatory cytokines, microbiota profile, and SCFAs, which may have consequences for gut health.

Phenotyping of subjects for large scale studies on patients with IBS.

BACKGROUND: Irritable bowel syndrome (IBS) is a complex condition with multiple factors contributing to its aetiology and pathophysiology. Aetiologically these include genetics, life-time events and environment, and physiologically, changes in motility, central processing, visceral sensitivity, immunity, epithelial permeability and gastrointestinal microflora. Such complexity means there is currently no specific reliable biomarker for IBS, and thus IBS continues to be diagnosed and classified according to symptom based criteria, the Rome Criteria. Carefully phenotyping and characterisation of a 'large' pool of IBS patients across Europe and even the world however, might help identify sub-populations with accuracy and consistency. This will not only aid future research but improve tailoring of treatment and health care of IBS patients. PURPOSE: The aim of this position paper is to discuss the requirements necessary to standardize the process of selecting and phenotyping IBS patients and how to organise the collection and storage of patient information/samples in such a large multi-centre pan European/global study. We include information on general demographics, gastrointestinal symptom assessment, psychological factors, quality of life, physiological evaluation, genetic/epigenetic and microbiota analysis, biopsy/blood sampling, together with discussion on the organisational, ethical and language issues associated with implementing such a study. The proposed approach and documents selected to be used in such a study was the result of a thoughtful and thorough four-year dialogue amongst experts associated with the European COST action BM1106 GENIEUR (www.GENIEUR.eu).

Postinfectious and sporadic functional gastrointestinal disorders have different prevalences and rates of overlap: results from a controlled cohort study 3 years after acute giardiasis.

BACKGROUND: Irritable bowel syndrome (IBS) is a common complication following gastroenteritis, and a high prevalence of postgiardiasis IBS has previously been reported. This study aims to investigate the prevalence, adjusted relative risk (RRadj), and overlap of different functional gastrointestinal disorders (FGID) according to Rome III criteria following infection with Giardia lamblia. METHODS: All patients ≥18 years of age with verified giardiasis during an outbreak in 2004, and a control group matched by age and gender, were mailed a questionnaire 3 years later. KEY RESULTS: The prevalence of functional dyspepsia (FD) was 25.9% in the exposed and 6.9% in the control group, RRadj: 3.9 (95% confidence intervals [CI]: 3.1-4.8). The prevalence of IBS was 47.9% and 14.3%, respectively, with RRadj: 3.4 (95% CI: 3.0-3.8). Prevalence of other gastrointestinal symptoms ranged from 70.0% vs 39.7% for bloating (RRadj: 1.8) to 8.3% vs 2.9% for nausea (RRadj: 3.0) in the Giardia and the control group, respectively. Among individuals fulfilling criteria for IBS 44% in the exposed group and 29% in the control group also fulfilled criteria for FD. IBS subtypes based on Rome III criteria (stool consistency) showed poor agreement with subtypes based on frequency of bowel movements (Kappa-values: 0.17 and 0.27). CONCLUSIONS & INFERENCES: There were high prevalences and RRs of IBS, FD and other gastrointestinal symptoms following acute giardiasis, and a high degree of overlap between the disorders. The agreement between different IBS subtype criteria varied, and there were also differences between the exposed and control group.

Dietary guidance normalizes large intestinal endocrine cell densities in patients with irritable bowel syndrome.

BACKGROUND/OBJECTIVES: To determine the large intestinal endocrine cell types affected following dietary guidance in patients with irritable bowel syndrome (IBS). SUBJECTS/METHODS: The study included 13 IBS patients and 13 control subjects. The patients received three sessions of individualized dietary guidance. Both the control subjects and the patients were scheduled for colonoscopies at baseline and again for the patients at 3-9 months after dietary guidance. Biopsy samples were taken from the colon and rectum and were immunostained for all types of large intestinal endocrine cells. The endocrine cells were quantified using computerized image analysis. RESULTS: The daily total consumption (mean±s.e.m. values) of fruits and vegetables rich in FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) decreased significantly from 16.2±5.3 g before receiving dietary guidance to 9.2±3.2 g after receiving dietary guidance (P=0.02). In the total colon, the densities of serotonin cells were 46.8±8.9, 10.5±2.1 and 22.6±3.2 cells/mm(2) in control subjects and in IBS patients before and after receiving dietary guidance, respectively (P=0.007); the corresponding densities of peptide YY cells were 11.6±1.8, 10.8±1.7 and 16.8±2.1 cells/mm(2), respectively (P=0.06). The cell densities for both serotonin and peptide YY did not change significantly in the rectum. The densities of somatostatin cells in the rectum were 13.5±3.0, 13.2±3.0, and 22.3±3.2 cells/mm(2) for control subjects and for IBS patients before and after receiving dietary guidance, respectively (P=0.01). CONCLUSIONS: The densities of the large intestinal endocrine cells tend to normalize following dietary guidance that may have contributed to the improvement of the patients with IBS symptoms.

Effect of dietary management on the gastric endocrine cells in patients with irritable bowel syndrome.

BACKGROUND/OBJECTIVES: The gastric endocrine cells in patients with irritable bowel syndrome (IBS) tend to normalize following dietary guidance. The aim of the present study was to identify the gastric endocrine cell types that are changed following such dietary guidance. SUBJECTS/METHODS: Fourteen IBS patients and 14 healthy subjects were included in the study. Patients received three sessions of individual dietary management guidance. Gastroscopy was performed on both the controls and the patients at baseline and then again for the patients at 3-9 months after dietary guidance. Biopsy samples from the corpus and antrum were immunostained for all gastric endocrine cell types. Endocrine cells were quantified by computerized image analysis. RESULTS: The densities of the ghrelin cells for the controls and IBS patients before and after dietary guidance were 149.6 ± 36.2 (mean ± s.e.m.; 95% confidence interval (CI) 71.3-227.8), 114.5 ± 32.7 and 161.8 ± 37.8 cells/mm(2), respectively. The densities of the gastrin cells in these groups were 155.8 ± 21.0 (95% CI 110.3-201.2), 159.4 ± 24.3 and 211.6 ± 28.0 cells/mm(2), respectively; the corresponding densities of serotonin cells in the corpus were 18.2 ± 3.9 (95% CI 9.8-26.6), 10.6 ± 3.4 and 14 ± 2.0 cells/mm(2) and in the antrum were 44.6 ± 12.2 (95% CI 18.1-71.1), 1.7 ± 0.5 and 14.7 ± 6.3 cells/mm(2). The densities of the somatostatin cells in the corpus were 40.0 ± 7.7 (95% CI 23.5-56.5), 23.0 ± 3.0 and 37.3 ± 4.2 cells/mm(2), respectively, and in the antrum were 138.9 ± 22.0 (95% CI 91.4-186.3), 95.6 ± 15.9 and 86.0 ± 16.9 cells/mm(2), respectively. CONCLUSIONS: The densities of all of the gastric endocrine cell types changed towards the healthy control values in the IBS patients following a change in food intake.

Mesenteric blood flow, glucose absorption and blood pressure responses to small intestinal glucose in critically ill patients older than 65 years.

PURPOSE: To compare nutrient-stimulated changes in superior mesenteric artery (SMA) blood flow, glucose absorption and glycaemia in individuals older than 65 years with, and without, critical illness. METHODS: Following a 1-h 'observation' period (t (0)-t (60)), 0.9 % saline and glucose (1 kcal/ml) were infused directly into the small intestine at 2 ml/min between t (60)-t (120), and t (120)-t (180), respectively. SMA blood flow was measured using Doppler ultrasonography at t (60) (fasting), t (90) and t (150) and is presented as raw values and nutrient-stimulated increment from baseline (Δ). Glucose absorption was evaluated using serum 3-O-methylglucose (3-OMG) concentrations during, and for 1 h after, the glucose infusion (i.e. t (120)-t (180) and t (120)-t (240)). Mean arterial pressure was recorded between t (60)-t (240). Data are presented as median (25th, 75th percentile). RESULTS: Eleven mechanically ventilated critically ill patients [age 75 (69, 79) years] and nine healthy volunteers [70 (68, 77) years] were studied. The magnitude of the nutrient-stimulated increase in SMA flow was markedly less in the critically ill when compared with healthy subjects [Δt (150): patients 115 (-138, 367) versus health 836 (618, 1,054) ml/min; P = 0.001]. In patients, glucose absorption was reduced during, and for 1 h after, the glucose infusion when compared with health [AUC(120-180): 4.571 (2.591, 6.551) versus 11.307 (8.447, 14.167) mmol/l min; P < 0.001 and AUC(120-240): 26.5 (17.7, 35.3) versus 40.6 (31.7, 49.4) mmol/l min; P = 0.031]. A close relationship between the nutrient-stimulated increment in SMA flow and glucose absorption was evident (3-OMG AUC(120-180) and ∆SMA flow at t (150): r (2) = 0.29; P < 0.05). CONCLUSIONS: In critically ill patients aged >65 years, stimulation of SMA flow by small intestinal glucose infusion may be attenuated, which could account for the reduction in glucose absorption.

Rome III subgroups of functional dyspepsia exhibit different characteristics of antral contractions measured by strain rate imaging - a pilot study.

PURPOSE: Rome III defines two distinct entities of functional dyspepsia (FD), namely epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS). We aimed at studying these subgroups of FD by simultaneously assessing antral strain, gastric accommodation and emptying and visceral hypersensitivity. MATERIALS AND METHODS: Strain during antral contractions was assessed by ultrasound strain rate imaging in 15 controls and 19 FD patients (8 EPS patients and 11 PDS patients). Gastric accommodation and emptying were assessed using B-mode ultrasonography. Symptoms were assessed by visual analogue scale (VAS). RESULTS: During fasting, antral strain in EPS patients (mean±SEM) was 61.4 ±â€Š6.4 %, significantly higher than in controls (47.5 ±â€Š3.3 %; p = 0.042) and in PDS patients (28.6 ±â€Š1.7 %; p = 0.001). PDS patients had lower strain than controls (p < 0.001). Postprandially, EPS patients had higher strain than both controls and PDS patients (p < 0.01) but no difference was found between controls and PDS patients. Compared with controls, PDS patients had significantly larger fasting proximal area than controls (14.9 ±â€Š1.6 cm2 vs. 7.8 ±â€Š0.2 cm2; p < 0.001), whereas EPS patients did not differ (12.1 ±â€Š1.9 cm2; p = 0.057). Gastric emptying fraction (1 - proximal area at 40 min postprandially/area at 1 min postprandial × 100) at 40 min postprandially in EPS patients 46.4 ±â€Š6.6 % was lower than in controls (62.9 ±â€Š1.3 %; p = 0.032), but higher than PDS patients (27.4 ±â€Š5.3 %; p = 0.018). CONCLUSION: Anterior radial strain measured by ultrasound strain rate imaging may discriminate between subgroups of FD and healthy controls. This study supports the Rome III classification of FD into EPS and PDS groups.

Chromogranin A cell density in the rectum of patients with irritable bowel syndrome.

In a previous study, chromogranin A (CgA) cell density in the colon of patients with irritable bowel syndrome (IBS) was found to be reduced. It has been suggested that intestinal CgA cell density may be used as a marker for the diagnosis of IBS. The rectum harbours a larger number of large intestinal endocrine cells and is more accessible for biopsies than the colon. The present study aimed at determining the CgA cell density in the rectum of IBS patients. A total of 47 patients with IBS that fulfilled the Rome Criteria III (39 females and 8 males; average age, 38 years) were included. A total of 28 patients had diarrhea (IBS-D) and 19 had constipation (IBS-C) as the predominant symptom. A total of 27 subjects that underwent colonoscopy with rectal biopsies were used as the controls. These subjects underwent colonoscopy due to gastrointestinal bleeding (the source of which was identified as haemorrhoids or angiodysplasia; 19 females and 8 males; average age, 49 years), or health worries. The rectal biopsies were immunostained for CgA and quantified by computer image analysis. The CgA density in the controls was 206.3±22.2 (mean ± SEM), in all IBS patients 190.2±14.3, in IBS-D patients 188.8±14.7 and in IBS-C patients 195.3±34.1. There was no statistically significant difference between the controls, IBS, IBS-D or IBS-C patients (P=0.5, 0.5 and 0.7, respectively). The present study showed that although the rectum comprises the same endocrine cell types as the colon, attention must be paid when drawing conclusions regarding the whole large intestine from studies carried out on the rectum. This particularly applies when endocrine cells are investigated. As CgA cell density represents the total endocrine cell content of the rectum, changes in specific endocrine cells in IBS patients cannot be excluded.

Gastrointestinal wall thickness measured with transabdominal ultrasonography and its relationship to demographic factors in healthy subjects.

PURPOSE: To describe the gastrointestinal (GI) wall thickness and the thickness of individual wall layers in healthy subjects using ultrasound and to determine whether demographic factors, the ultrasound transducer frequency, or a fasting state influences these measurements. MATERIALS AND METHODS: After overnight fasting, the GI wall thickness and wall layers were measured in several regions with transabdominal, high-frequency ultrasound. 122 healthy subjects aged 23 - 79 were included. All measurements were performed with both 8 and 12-MHz transducers except for the rectum measurement (4 MHz). 23 patients were given a 300 Kcal test meal and re-examined after 30 minutes. RESULTS: Wall thickness measurements of the GI tract with transabdominal ultrasonography are dependent on transducer frequency (p < 0.001), weight (p < 0.001) and age (p < 0.018). The thickness of individual wall layers in the ileum and the sigmoid colon was found to be dependent on both age (p = 0.007) and weight (p < 0.001). The mean wall thickness from the jejunum to the sigmoid colon ranged from 0.9 to 1.2 mm with standard deviations (SD) of 0.3 mm or less. The mean (SD) was 2.9 (0.8) mm in the gastric antrum, 1.6 (0.3) mm in the duodenum, and 2.1 (0.5) mm in the rectum. The gastric antrum was thinner and the ileum and sigmoid colon were thicker after the test meal (p < 0.05). CONCLUSION: GI wall thickness depends on weight and age. Provided adequate measurement, an abnormal GI wall should be suspected if the thickness exceeds 2 mm except for in the gastric antrum, duodenum and rectum. Reference values for wall thickness can be used regardless of fasting state or probe frequency except for in the gastric antrum.

The role of diet in the pathogenesis and management of irritable bowel syndrome (Review).

Most patients with irritable bowel syndrome (IBS) believe that diet plays a significant role in inducing IBS symptoms and desire to know what foods to avoid. It has been found that the intake of calories, carbohydrates, proteins and fat by IBS patients does not differ from that of the background population. IBS patients were found to avoid certain food items that are rich in fermentable oligo-, di- and monosacharides and polyols (FODMAPs), but they did have a high consumption of many other FODMAP-rich food items. The diet of IBS patients was found to consist of a low calcium, magnesium, phosphorus, vitamin B2 and vitamin A content. There is no consistent evidence that IBS patients suffer from food allergy, nor is there documented evidence that food intolerance plays a role in IBS symptoms. Abnormalities in gut hormones have been reported in IBS patients. As gut hormones control and regulate gastrointestinal motility and sensation, this may explain the abnormal gastrointestinal motility and visceral hypersensitivity reported in these patients. Guidance concerning food management which includes individually based restrictions of FODMAP-rich food items and individual evaluation of the effects of protein-, fat- and carbohydrate-rich/poor diets may reduce IBS symptoms.

Low densities of serotonin and peptide YY cells in the colon of patients with irritable bowel syndrome.

BACKGROUND: The gut hormones are important in regulating gastrointestinal motility. Disturbances in gastrointestinal motility have been reported in patients with irritable bowel syndrome (IBS). Reduced endocrine cell density, as revealed by chromogranin A, has been reported in the colon of IBS patients. AIMS: To investigate a possible abnormality in the colonic endocrine cells of IBS patients. METHODS: A total of 41 patients with IBS according to Rome Criteria III and 20 controls were included in the study. Biopsies from the right and left colon were obtained from both patients and controls during colonoscopy. The biopsies were immunostained for serotonin, peptide YY (PYY), pancreatic polypeptide (PP), entroglucagon, and somatostatin cells. Cell densities were quantified by computerized image analysis. RESULTS: Serotonin and PYY cell densities were reduced in the colon of IBS patients. PP, entroglucagon, and somatostatin-immunoreactive cells were too few to enable reliable quantification. CONCLUSION: The cause of these observations could be primary genetic defect(s), secondary to altered serotonin and/or PYY signaling systems and/or subclinical inflammation. Serotonin activates the submucosal sensory branch of the enteric nervous system and controls gastrointestinal motility and chloride secretion via interneurons and motor neurons. PYY stimulates absorption of water and electrolytes, and inhibits prostaglandin (PG) E2, and vasoactive intestinal peptide, which stimulates intestinal fluid secretion and is a major regulator of the "ileal brake". Although the cause and effect relationship of these findings is difficult to elucidate, the abnormalities reported here might contribute to the symptoms associated with IBS.

Measurement of gastric emptying of a high-nutrient liquid by 3D ultrasonography in diabetic gastroparesis.

BACKGROUND: Gastric emptying (GE) is delayed in 30-50% of patients with longstanding diabetes. Scintigraphy represents the 'gold standard' for measurement of GE, but is associated with a radiation burden. Three-dimensional (3D) ultrasonography has recently been demonstrated to provide a valid measure of liquid GE in healthy subjects; however, the technique has not been validated in patients with gastroparesis. The primary aim of this study was to compare measurements of GE of a high-nutrient glucose drink by 3D ultrasonography and scintigraphy in diabetic gastroparesis. METHODS: Ten patients (eight type 1, two type 2, 6M, 4F, aged 46.1 ± 4.5 years, BMI 29.1 ± 1.6 kg m(-2), duration 19.6 ± 3.3 years) with diabetic gastroparesis [defined as retention at 100 min of solid (100 g minced beef) ≥ 61% and/or 50% emptying time (T50) of liquid (150 mL 10% dextrose) ≥ 31 min], were studied. Concurrent measurements of GE by scintigraphy and 3D ultrasonography were performed following ingestion of 75 g glucose in 300 mL water labeled with 20 MBq (99m) Tc-sulfur colloid. KEY RESULTS: There was no significant difference in GE between the two techniques (T50s: scintigraphy - 103.3 ± 10.0 min VS 3D ultrasonography - 98.8 ± 10.4 min; P = 0.60). There was a significant correlation between scintigraphic and ultrasonographic T50s (r = 0.67, P = 0.03). The limits of agreement for the T50s were -57.22 min and +48.22 min (mean difference -4.5 min). Blood glucose after the drink was greater when GE was relatively more rapid (e.g. at t = 60 min; scintigraphy: r = -0.65, P = 0.04; 3D ultrasonography: r = -0.78, P = 0.008). CONCLUSIONS & INFERENCES: Three-dimensional ultrasonography appears to provide a valid, and non-invasive, measure of GE of high-nutrient liquids in diabetic gastroparesis.

Abnormal small-intestinal endocrine cells in patients with irritable bowel syndrome.

BACKGROUND: General disturbances in gastrointestinal motility have been reported in patients with irritable bowel syndrome (IBS). The gastrointestinal tract hormones play an important role in regulating gastrointestinal motility. AIMS: To investigate a possible abnormality in the small intestinal endocrine cells of IBS patients. METHODS: Included in the study were 41 patients with irritable bowel syndrome according to Rome Criteria III and 42 healthy controls. Duodenal biopsies were obtained from both patients and controls during gastroscopy. The biopsies were immunostained by avidin-biotin-complex method for secretin, CCK, GIP, somatostatin, and serotonin cells. The cell densities were quantified by computerized image analysis. RESULTS: The density of secretin- and CCK-immunoreactive cells in patients with IBS was significantly reduced. The reduction in secretin and CCK cells occurred only in IBS-diarrhea patients, but not in IBS-constipation subtype. Both GIP and somatostatin cell densities were reduced in the duodenum of IBS patients. There was no statistical difference between the subtypes of IBS patients, regarding secretin, CCK, GIP, or somatostatin cell densities. Serotonin cell density was not affected in patients with IBS. CONCLUSIONS: The low densities of secretin and CCK cells in IBS-diarrhea patients may cause a functional pancreatic insufficiency as well as inadequate gall emptying, as these hormones stimulate pancreatic bicarbonate and enzyme secretion and CCK stimulates as well gall bladder contraction. Low densities of secretin, GIP, and somatostatin cells in IBS patients might result in a high secretion of gastric acid, as secretin, GIP, and somatostatin inhibit gastric acid secretion.

Relative importance of abnormalities of CCK and 5-HT (serotonin) in Giardia-induced post-infectious irritable bowel syndrome and functional dyspepsia.

BACKGROUND: Post-infectious irritable bowel syndrome (PI-IBS) and functional dyspepsia (FD) have been described after both Campylobacter jejuni gastroenteritis and Giardia infection. After C. jejuni, there is increased rectal serotonin (5-HT)-containing EC cells and postprandial plasma 5-HT, while a pilot study suggested increased plasma cholecystokinin (CCK) after Giardia infection. AIM: To determine changes in plasma and duodenal mucosal 5-HT and CCK in Giardia-induced PI-IBS. METHODS: A total of 32 patients previously infected with Giardia and 19 who had recovered fully (controls) completed symptom questionnaires. Endoscopic duodenal biopsies were obtained from all subjects and immunohistochemically stained for CCK, 5-HT and CgA containing entero-endocrine cells and mast cells. 5-HT content was also assessed. Twenty-one of 32 patients and 19 controls consumed a high-carbohydrate meal, while fasting and postprandial plasma CCK and 5-HIAA were measured. RESULTS: Post-infectious irritable bowel syndrome patients had increased numbers of CCK cells (P = 0.02), but lower numbers of EC cells (P = 0.009). Plasma CCK did not differ significantly between the groups, but correlated significantly with postprandial dyspepsia scores (r = 0.5, P = 0.05). PI-IBS patients had significantly lower plasma 5-HIAA, before and after meal (P = 0.05) as well as more dyspepsia (P < 0.0001) compared with recovered subjects. CONCLUSIONS: Post-infectious bowel dysfunction following Giardia infection is associated with increased duodenal mucosal CCK. Postprandial dyspeptic symptoms correlate better with CCK than measures of 5-HT metabolism.

The nitric oxide synthase inhibitor, Ng-nitro-L-arginine-methyl-ester, attenuates the delay in gastric emptying induced by hyperglycaemia in healthy humans.

The aim of this study was to determine whether the nitric oxide (NO) synthase inhibitor, N(g)-nitro-L-arginine-methyl-ester (L-NAME), reverses the effects of acute hyperglycaemia on gastric emptying and antropyloroduodenal (APD) motility. The study had a four-way randomized crossover (hyperglycaemia vs euglycaemia; L-NAME vs placebo) design in a clinical laboratory setting. Seven healthy volunteers [four males; age 30.3 +/- 3.8 years; body mass index (BMI) 23.6 +/- 1.2 kg m(-2)] were the study subjects. After positioning a transnasal manometry catheter across the pylorus, the blood glucose concentration was maintained at either 15 or 5 mmol L(-1) using a glucose/insulin clamp. An intravenous infusion of L-NAME (180 microg kg(-1 )h(-1)) or placebo (0.9% saline) was commenced (T = -30 min) and continued for 150 min. At T = -2 min, subjects ingested a drink containing 50 g of glucose made up to 300 mL with water. Gastric emptying was measured using 3D ultrasound, and APD motility using manometry. Hyperglycaemia slowed gastric emptying (P < 0.05), and this effect was abolished by L-NAME. L-NAME had no effect on gastric emptying during euglycaemia. Hyperglycaemia suppressed fasting antral motility [motility index: 3.9 +/- 0.8 (hyperglycaemia) vs 6.5 +/- 0.6 (euglycaemia); P < 0.01]; l-NAME suppressed postprandial antral motility [motility index: 3.6 +/- 0.2 (L-NAME) vs 5.1 +/- 0.2 (placebo); P < 0.001]. Postprandial basal pyloric pressure was higher during hyperglycaemia (P < 0.001), and lower after administration of L-NAME (P < 0.001). Slowing of gastric emptying induced by hyperglycaemia is mediated by NO, and may involve the modulation of tonic pyloric activity.

Strain measurement during antral contractions by ultrasound strain rate imaging: influence of erythromycin.

Strain rate imaging (SRI) is a non-invasive ultrasound (US) modality that enables the study of mechanical deformation (strain) with high spatial and temporal resolution. A total of 244 contractions in seven healthy volunteers were studied by SRI on two separate days to characterize radial strain of antral contractions in the fasting and fed states and to assess the influence of intravenous erythromycin. Gastric accommodation and emptying were assessed by 2D ultrasonography. The perception of hunger was registered by the participants. The strain increased from early to late phase II and phase III activity by (median) 18%, 58% and 82%, respectively, P < 0.05. Erythromycin infusion in phase I induced contractions with median strain of 35%, but did not increase postprandial strain. Both fasting and postprandially, lumen-occlusive contractions with erythromycin were more frequent than in naturally occurring contractions, 69%vs 48%, P = 0.036 and 40%vs 5%, P < 0.001 respectively. All subjects had rumbling in their abdomens when intraluminal air was detected sonographically (85% of all phase III contractions) and that rumbling was perceived by the participant as maximal awareness of hunger. SRI enabled detailed strain measurement of individual antral contractions. Erythromycin initiated fasting antral contractions and increased the number of lumen-occlusive contractions.

Vagal activation by sham feeding improves gastric motility in functional dyspepsia.

Antral hypomotility and impaired gastric accommodation in patients with functional dyspepsia have been ascribed to vagal dysfunction. We investigated whether vagal stimulation by sham feeding would improve meal-induced gastric motor function in these patients. Fourteen healthy volunteers and 14 functional dyspepsia patients underwent a drink test twice, once with and once without simultaneous sham feeding. After ingesting 500 mL clear meat soup (20 kcal, 37 degrees C) in 4 min, sham feeding was performed for 10 min by chewing a sugar-containing chewing gum while spitting out saliva. Using two- and three-dimensional ultrasound, antral motility index (contraction amplitude x frequency) and intragastric volumes were estimated. Without sham feeding, functional dyspepsia patients had lower motility index than healthy volunteers (area under curve 8.0 +/- 1.2 vs 4.4 +/- 1.0 min(-1), P = 0.04). In functional dyspepsia patients, but not in healthy volunteers, motility index increased and intragastric volume tended to increase by sham feeding (P = 0.04 and P = 0.06 respectively). The change in motility index was negatively correlated to the change in pain score (r = -0.59, P = 0.007). In functional dyspepsia patients, vagal stimulation by sham feeding improves antral motility in response to a soup meal. The result supports the view that impaired vagal stimulation is implicated in the pathogenesis of gastric motility disturbances in functional dyspepsia.

Increased visceral sensitivity in Giardia-induced postinfectious irritable bowel syndrome and functional dyspepsia. Effect of the 5HT3-antagonist ondansetron.

In an outbreak of waterborne giardiasis where 1300 subjects were diagnosed, with Giardia lamblia, 139 continued to have abdominal symptoms of whom two of three had negative stool culture and microscopy. These were considered to have a postinfectious functional gastrointestinal disorder. We investigated visceral hypersensitivity in patients with persisting abdominal symptoms after Giardia infection and assessed the effect of 5HT(3)-antagonist ondansetron. Twenty-two patients with Giardia negative stools and 19 controls were included. A subset of patients (n = 15) had both irritable bowel syndrome (IBS) and functional dyspepsia (FD). All subjects underwent a satiety test with a soup combined with three-dimensional ultrasound. Fifteen of 22 patients underwent double-blind, randomized, placebo-controlled study with the 5-HT(3) antagonist ondansetron given orally. Drinking capacity was lower in patients than in controls (P < 0.01) and gastric emptying was reduced (P < 0.05). Patients had more symptoms both fasting and postprandially (P < 0.001) compared to controls. Ondansetron had no effect on these parameters except from less nausea postprandially (P < 0.05). In conclusion, patients with Giardia-induced gastrointestinal symptoms developed both IBS and FD. They exhibited gastric hypersensitivity with lower drinking capacity and delayed gastric emptying. The 5-HT(3) antagonist ondansetron did not improve drinking capacity, gastric emptying or symptoms except nausea.