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.

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.

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.

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.

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.

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.

Distension-induced gastric accommodation in functional dyspepsia: effect of autonomic manipulation.

Functional dyspepsia (FD) is associated with impaired gastric accommodation and autonomic dysregulation. The aim of this study was to investigate the effects of autonomic manipulation on distension-induced gastric accommodation in subjects with and without FD, using a newly developed gastric barostat paradigm. Twelve healthy subjects (HS) and 18 subjects with FD had four barostat examinations each: no intervention, intravenous atropine (1 mg), vagal stimulation (mental relaxation with deep breathing) and acute stress stimulation (serial subtraction task). Intrabag pressure increased from 1 to 15 mmHg in 5 min (ramp phase), and was maintained at 15 mmHg for 5 min (tonic phase). Volume responses were analysed using predefined parameters. There were no significant group differences in accommodation variables between HS and subjects with FD. The FD group could be subdivided into two distinct subgroups: subgroup 1 (n = 7, 38%) with low maximum volume and accommodation rate, and subgroup 2 with normal accommodation (n = 11). In subgroup 1, but not in subgroup 2 atropine increased maximum volume and accommodation rate substantially. Neither mental stress nor mental relaxation changed any of the accommodation variables. In a subgroup of subjects with FD, impairment of distension-induced gastric accommodation can be improved by cholinergic blockade, but not by acute physiological autonomic manipulation.

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.

Measurements of gastric emptying of low- and high-nutrient liquids using 3D ultrasonography and scintigraphy in healthy subjects.

Scintigraphy represents the 'gold standard' for the measurement of gastric emptying. Recent studies suggest that three-dimensional (3D) ultrasonography may allow a precise measure of gastric emptying, given the capacity for accurate volume calculations of the stomach. The aim of this study was to compare measurements of gastric emptying of both low- and high-nutrient drinks by 3D ultrasonography with scintigraphy. Ten healthy young subjects (6M, 4F, age 23.5 +/- 1.5 years) were studied on 2 days. Concurrent measurements of gastric emptying by scintigraphy and 3D ultrasonography were performed after ingestion of 500 mL beef soup (12 kcal) or 300 ml dextrose (25% w/v) (314 kcal) labelled with 20 MBq (99m)Tc-sulphur colloid. There was no significant difference between scintigraphic and ultrasonographic 50% emptying times (T50s) (soup: 27.7 +/- 4.8 min vs 23.8. +/- 4.8 min; dextrose: 122.2 +/- 13.3 min vs 131.9 +/- 10.2 min). There was a close correlation between scintigraphic and ultrasonographic T50s for both soup (r = 0.92, P = 0.0005) and dextrose (r = 0.88, P = 0.0007). For the T50s, the limits of agreement were -15.2 min and +8.1 min for the soup (mean difference -3.6 min) and -35.3 min and +47.6 min for dextrose (mean difference +6.2 min). 3D ultrasonography provides a valid measure of gastric emptying of liquid meals in healthy subjects.

A multimodal laser Doppler and endosonographic distension device for studying mechanosensation and mucosal blood flow in the oesophagus.

We describe the development of a multimodal device combining bag distension, manometry, high frequency intraluminal ultrasound, laser Doppler flowmetry and symptom registration. Bench tests showed that the different modalities did not influence each other. During bag distension we obtained high quality images of the oesophageal wall for computing biomechanical parameters, and laser Doppler signals showing variation in mucosal perfusion. We conclude that the principle of measurement is sound and that the device can provide a basis for further studies.

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.

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.

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).

Effects of ferrous sulphate and non-ionic iron-polymaltose complex on markers of oxidative tissue damage in patients with inflammatory bowel disease.

BACKGROUND: Iron deficiency is a common complication of inflammatory bowel disease. Oral iron therapy may reinforce intestinal tissue injury by catalyzing production of reactive oxygen species. AIM: To compare the effects of ferrous sulphate and non-ionic iron-polymaltose complex on markers of oxidative tissue damage and clinical disease activity in patients with inflammatory bowel disease. METHODS: Forty-one patients with inflammatory bowel disease and iron deficiency were randomized to treatment with ferrous sulphate 100 mg twice a day or iron-polymaltose complex 200 mg once a day for 14 days. RESULTS: Following ferrous sulphate, plasma malondialdehyde increased (P = 0.02), while urine 8-isoprostaglandin F(2alpha) and plasma antioxidants did not change significantly. Iron-polymaltose complex did not change plasma malondialdehyde, urine 8-isoprostaglandin F(2alpha) or plasma antioxidants. Comparing the two treatments, changes in plasma malondialdehyde tended to differ (P = 0.08), while urine 8-isoprostaglandin F(2alpha) and plasma antioxidants did not differ. Neither ferrous sulphate nor iron-polymaltose complex altered clinical disease activity indices. CONCLUSIONS: Ferrous sulphate increased plasma malondialdehyde, a marker of lipid peroxidation. Comparing treatment with ferrous sulphate and iron-polymaltose complex, changes in plasma malondialdehyde tended to differ. Clinical disease activity was unchanged after both treatments.

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.

Spiramycin in triple therapy of Helicobacter pylori-associated peptic ulcer disease. An open pilot study with 12-month follow-up.

BACKGROUND: Spiramycin (Rovamycin) is a well-established macrolide antibiotic with good anti-Helicobacter pylori activity in vitro. It is acid-stable and found in high concentration in various body fluids and cells after oral administration. Its anti-H. pylori activity in vivo has not yet been tested. METHODS: Twenty-five consecutive patients with endoscopically verified peptic ulcer and a positive biopsy urease test were given spiramycin tables 1.5 MIU instead of oxytetracycline 500 mg q.d.s. in our triple therapy regimen with bismuth subnitrate suspension 10 mL (150 mg bismuth subnitrate) q.d.s. and metronidazole 400 mg t.d.s. for 10 days. Bismuth was taken between meals and spiramycin and metronidazole with meals. Re-endoscopy and 14C-urea breath test were performed 4 weeks after completion of therapy. Those who were H. pylori negative according to the breath test returned for 1-year follow-up. RESULTS: Per protocol analysis at 4 weeks showed that 21 out of 23 patients were H. pylori negative and had healed ulcers. These 21 patients were persistingly H. pylori negative and had no ulcers at 1-year follow-up. H. pylori eradication and ulcer healing rates were thus 91.3%; 95% confidence interval from 72.0% to 98.9%. Side-effects limiting daily activity were significantly less frequent than we have experienced previously using oxytetracycline in triple therapy. CONCLUSIONS: Spiramycin appears to be an alternative to tetracycline in the triple therapy of H. pylori infection. Further studies to position spiramycin as an anti-H. pylori drug are warranted.

Spiramycin is comparable to oxytetracycline in eradicating H. pylori when given with ranitidine bismuth citrate and metronidazole.

BACKGROUND: We have consistently achieved about 90% eradication of H. pylori with liquid bismuth, metronidazole and oxytetracycline. AIM: To test eradication and adverse events of ranitidine bismuth citrate (RBC) when given with metronidazole and either oxytetracycline or spiramycin. METHODS: One hundred and eighty-three patients were randomized to one of four 10-day regimens: RBC400OM: RBC 400 mg b.d., oxytetracycline 500 mg q.d.s.; RBC400SM: RBC 400 mg b.d., spiramycin 1 g q.d.s.; RBC200OM: RBC 200 mg q.d.s., oxytetracycline 500 mg q.d.s.; RBC200SM: RBC 200 mg q.d.s., spiramycin 1 g q.d.s. Additionally, all patients received metronidazole 400 mg q.d.s. A 14C-urea breath test was performed at 8 weeks. RESULTS: Intention-to-treat eradication rates were 94%, 91%, 94% and 89% with RBC400OM, RBC400SM, RBC200OM and RBC200SM, respectively (P = 0.81). Eradication was significantly higher in ulcer patients (97%) than in those with diagnoses other than ulcer (86%) (P = 0.009). There was a strong tendency to better eradication among those who had never smoked (100%) compared with ex-smokers (93%) and smokers (89%) (P = 0.06). Fifty-three per cent experienced at least one moderate or severe adverse event, and women had more adverse events than men (P = 0.0002). CONCLUSIONS: All four regimens had comparable efficacy and adverse events. Eradication was significantly better in ulcer patients but there was a trend to better eradication in those who smoked less, used less alcohol and exercised more. Adverse events were frequent, perhaps because of the large dose of metronidazole used, but few patients stopped treatment.

Low antroduodenal pressure gradients are responsible for gastric emptying of a low-caloric liquid meal in humans.

The motor mechanisms responsible for transpyloric flow of gastric contents are still poorly understood. The aim of our study was to investigate the relationship between luminal pressures and gastric wall motion and between gastroduodenal pressure gradients and pressure waves, and ante- and retro-grade transpyloric flow. In eight healthy volunteers, intraluminal pressures were recorded from the antrum and proximal duodenum. Transpyloric flow was monitored simultaneously using duplex ultrasonography, before, during and after ingestion of 300 mL meat soup. Transpyloric emptying occurred as sequences of alternating periods of emptying-reflux-emptying. Approximately one-third of the sequences were not associated with peristalsis. The antroduodenal pressure gradients were significantly lower during nonperistaltic-related emptying than during peristaltic-related emptying (0.15 (0-0.3) kPa, and 1.7 (0.2-2.0) kPa, respectively [mean plus minus (range)], P < 0.005). The duration of emptying episodes not associated with peristalsis were significantly longer than those associated with peristalsis at (6.5 (3-8.7) s and 4.4 (2-6) s, respectively, P=0.059). Manometry detected only 56% of the antral contractions seen on ultrasound. We concluded that gastric emptying of a low-calorie liquid meal occurs both during peristaltic and nonperistaltic antral activity. In spite of lower antroduodenal pressure gradients, the emptying episodes were longer for nonperistaltic emptying, which is likely to be caused by low pyloric resistance. Considerable flow seems to occur without peristalsis during gastric emptying of a low-calorie, liquid meal in humans.

Lower postprandial gastric volume response in diabetic patients with vagal neuropathy.

UNLABELLED: Poor relaxation in the stomach after a meal may contribute to disturbed gastric emptying and abdominal discomfort in patients with diabetes mellitus. In this study we aimed to compare barostat-recorded postprandial volume responses in these patients to those in healthy controls, and to study the relationship between the proximal volume responses, antral filling and vagal neuropathy. We compared 14 consecutively recruited patients with type 1 diabetes mellitus (DM) to 18 healthy controls (HC) with respect to meal-induced gastric volume response assessed by a barostat, antral area recorded by ultrasound, and vagal tone assessed by respiratory sinus arrhythmia (RSA). Meal-induced volume response of the proximal stomach (area under time-volume curve 0-30 min) was significantly (P = 0.04) lower in DM than in HC, 49.4 min.mL +/- 60.7 vs. 114.9 min.mL +/- 100.8. Antral area was significantly larger in DM than in HC, both fasting (4.3 cm2 +/- 1.9 vs. 3.0 cm2 +/- 0.9) and 10 min after ingestion of meat soup (11.8 cm2 +/- 3.4 vs. 8.8 cm2 +/- 2.9), P = 0.03 and P = 0.02, respectively. Vagal tone was significantly (P = 0.01) lower in DM than in HC. 3.7 beats min-1 +/- 2.3 vs. 6.1 beats min-1 +/- 2.2. No significant correlation was observed between the proximal volume responses and antral widening. Maximal gastric volume response correlated significantly with vagal tone (r = 0.77, P = 0.002). CONCLUSIONS: patients with diabetes mellitus type 1 have impaired meal-induced volume response, possibly as a consequence of reduced vagal tone.

Influence of a 5HT1 receptor agonist on gastric accommodation and initial transpyloric flow in healthy subjects.

Sumatriptan, a 5HT1 receptor agonist, inhibits antral motor activity, delays gastric emptying and relaxes the gastric fundus. The aim of this study was to characterize the effect of sumatriptan on transpyloric flow and gastric accommodation during and immediately after ingestion of a liquid meal using duplex sonography. Ten healthy subjects were investigated twice on separate days. In random order either sumatriptan 6 mg (Imigran 0.5 mL) or a placebo were given s.c. 15 min before ingesting 500 mL of a meat soup. The subjects were examined during the 3-min period before ingestion of the liquid meal, the 3-min spent drinking the meal and 10 min postprandially. Sumatriptan caused a significant widening of both the gastric antrum (P=0.02) and the proximal stomach (P=0.01) 10 min postprandially as compared with placebo. It caused no significant differences in time to initial gastric emptying (P=0.2), but significantly delayed commencement of peristaltic-related transpyloric flow (P=0.04). Sumatriptan had no significant effect on mean abdominal symptom scores, but after sumatriptan there was a significant negative correlation between width of postprandial antral area and postprandial nausea and between width of postprandial antral area and postprandial bloating. We therefore conclude that sumatriptan causes a postprandial dilatation of both the distal and the proximal stomach with no change in dyspeptic symptoms nor in length of time to first gastric emptying. Time to commencement of peristaltic-related emptying is delayed.