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Colorectal visceral hypersensitivity has been demonstrated in a subset of irritable bowel syndrome (IBS) patients. Serine protease and serotonergic signaling modulate gastrointestinal visceral sensitivity. We evaluated whether altered mucosal serine protease and serotonergic pathway components are related to rectal visceral hypersensitivity in IBS patients. Colorectal mucosal biopsies of 23 IBS patients and 15 controls were collected. Gene transcripts of protease-activated receptor (PAR)-2, trypsinogen IV, tryptophan hydroxylase (TPH)-1, and serotonin reuptake transporter (SERT) were quantified using real-time polymerase chain reaction. Substance P and 5-HT contents were measured by ELISA. The number of enterochromaffin cells, mast cells, and intraepithelial lymphocytes was determined using immunohistochemistry. Rectal visceral sensitivity was determined in IBS patients using barostat programmed for phasic ascending distension. Rectal hypersensitivity (+) and (−) IBS patients showed lower TPH-1 and SERT mRNA levels in the rectum compared with controls ( P ≤ 0.05). Rectal hypersensitivity (+) IBS patients ( n = 12) showed lower TPH-1 mRNA level in the sigmoid compared with controls ( P = 0.015). No significant differences were observed in PAR-2 and trypsinogen IV expression between controls and IBS patients. Rectal substance P content was increased in IBS patients compared with controls ( P = 0.045). No significant differences were found in transcript levels, cell counts, and substance P and 5-HT contents between rectal hypersensitivity (+) and (−) IBS patients. In conclusion, regardless of visceral hypersensitivity state, several serotonergic signaling components are altered in IBS patients.

Prophylactic probiotic therapy has shown beneficial effects in an experimental rat model for acute pancreatitis on the health status of the animals. Mechanisms by which probiotic therapy interferes with severity of acute pancreatitis and associated sepsis, however, are poorly understood. The aims of this study were to identify the probiotic-induced changes in the gut microbiota and to correlate these changes to disease outcome. Duodenum and ileum samples were obtained from healthy and diseased rats subjected to pancreatitis for 7 days and prophylactically treated with either a multispecies probiotic mixture or a placebo. Intestinal microbiota was characterized by terminal-restriction fragment length polymorphism (T-RFLP) analyses of PCR-amplified 16S rRNA gene fragments. These analyses showed that during acute pancreatitis the host-specific ileal microbiota was replaced by an “acute pancreatitis-associated microbiota.” This replacement was not reversed by administration of the probiotic mixture. An increase, however, was observed in the relative abundance of a novel bacterial phylotype most closely related to Clostridium lituseburense and referred to as commensal rat ileum bacterium (CRIB). Specific primers targeting the CRIB 16S rRNA gene sequence were developed to detect this phylotype by quantitative PCR. An ileal abundance of CRIB 16S rRNA genes of more than 7.5% of the total bacterial 16S rRNA gene pool was correlated with reduced duodenal bacterial overgrowth, reduced bacterial translocation to remote organs, improved pancreas pathology, and reduced proinflammatory cytokine levels in plasma. Our current findings and future studies involving this uncharacterized bacterial phylotype will contribute to unraveling one of the potential mechanisms of probiotic therapy.

Intestinal microbiota may play a role in the pathophysiology of irritable bowel syndrome (IBS). In this case–control study, mucosa-associated small intestinal and faecal microbiota of IBS patients and healthy subjects were analysed using molecular-based methods. Duodenal mucosal brush and faecal samples were collected from 37 IBS patients and 20 healthy subjects. The bacterial 16S rRNA gene was amplified and analysed using PCR denaturing gradient gel electrophoresis (DGGE). Pooled average DGGE profiles of all IBS patients and all healthy subjects from both sampling sites were generated and fingerprints of both groups were compared. The DGGE band fragments which were confined to one group were further characterized by sequence analysis. Quantitative real-time PCR (q-PCR) was used to quantify the disease-associated microbiota. Averaged DGGE profiles of both groups were identical for 78.2 % in the small intestinal samples and for 86.25 % in the faecal samples. Cloning and sequencing of the specific bands isolated from small intestinal and faecal DGGE patterns of IBS patients showed that 45.8 % of the clones belonged to the genus Pseudomonas, of which Pseudomonas aeruginosa was the predominant species. q-PCR analysis revealed higher levels (PP. aeruginosa in the small intestine of IBS patients (8.3 %±0.950) than in the small intestine of healthy subjects (0.1 %±0.069). P. aeruginosa was also significantly (PP. aeruginosa is detected more frequently and at higher levels in IBS patients than in healthy subjects, suggesting its potential role in the pathophysiology of IBS.

Background The parasitized or inflamed gastrointestinal mucosa shows an increase in the number of mucosal mast cells (MMC) and the density of extrinsic primary afferent nerve fibers containing the neuropeptide, calcitonin gene-related peptide (CGRP). Currently, the mode of action of CGRP on MMC is unknown. Methods The effects of CGRP on mouse bone marrow-derived mucosal mast cells (BMMC) were investigated by measurements of intracellular Ca2+ [Ca2+]i and release of mMCP-1. Key Results Bone marrow-derived mucosal mast cells responded to the application of CGRP with a single transient rise in [Ca2+]i. The proportion of responding cells increased concentration-dependently to a maximum of 19 ± 4% at 10−5 mol L−1 (mean ±SEM; C48/80 100%; EC50 10−8 mol L−1). Preincubation with the CGRP receptor antagonist BIBN4096BS (10−5 mol L−1) completely inhibited BMMC activation by CGRP [range 10−5 to 10−11 mol L−1; analysis of variance (anova)P

Background Intestinal barrier failure during acute pancreatitis (AP) is associated with translocation of luminal bacteria, resulting in infectious complications. We examined the effects of multispecies probiotics on the intestinal barrier impairment in a murine model of AP. Methods Mice were injected with cerulein to induce AP and were sacrificed 11 (early AP) or 72 hours (late AP) after start of induction. AP and associated systemic effects were confirmed by histology of pancreas and lung. Animals received daily probiotics starting 2 days prior to AP induction (pretreatment) or at the moment of AP induction (treatment). Mucosal barrier function of the distal ileum was assessed in Ussing chambers by measurement of the epithelial electrical resistance and the permeability to Na-fluorescein. Results Histological analysis revealed pancreatic injury in both phases of AP, and lung damage in the early phase. Epithelial resistance of the ileum was reduced and permeability increased in both phases of AP, indicating impairment of the intestinal barrier. Pretreatment had no effect on resistance or permeability in the early phase of AP. In the late phase of AP, pretreatment but not treatment abolished the AP induced resistance decrease and permeability increase. Administration of probiotics as such (ie, without induction of AP) had no effect on intestinal barrier function. Conclusion Pretreatment with multispecies probiotics for 2 days abolishes intestinal barrier dysfunction in the late phase of AP, while treatment does not. The effectiveness of probiotics in this model depends on the timing of administration. Clinical trials with probiotics should seek conditions where treatment can be started prior to onset of disease or elective surgical intervention.

Gastric electrical activity in a group of patients with severe nausea and repeated vomiting in the post-operative phase following major abdominal surgery (Group A, n = 21), was compared to that in a control group of patients without symptoms after colonic surgery (Group B, n = 14). Physical signs related to the digestive tract were assessed and electrical activity of the stomach was measured non-invasively by means of electrogastrography (EGG) and impedance gastrography (IGG). Two EGG/IGG recordings were performed in each patient. In group A the first recording was carried out after the onset of nausea and/or vomiting and a second control recording after disappearance of these symptoms and resumption of a normal diet. In group B the post-operative recording was performed on the second post-operative day, the control EGG/IGG signals were recorded pre-operatively. EGG and IGG could be successfully recorded in the post-operative phase, even in nauseated and vomiting patients. During post-operative nausea and vomiting power and frequency of the normal gastric myoelectrical activity (0.04–0.06 Hz) were not significantly lower than in the control recordings. In the first post-operative recordings (in Group A during nausea and vomiting and in Group B on the second post-operative day) an increased incidence of abnormal gastric frequencies (tachygastrias, 0.10–0.18 Hz) was observed in both groups. No significant difference between the groups was found. After nausea and vomiting had subsided in Group A, the incidence of tachygastrias was persistently high.

It was investigated which 5-hydroxytryptamine (5-HT) receptors mediate the responses to 5-HT in the longitudinal muscle layer of the guinea-pig proximal colon, using selective 5-HT receptor antagonists and the 5-HT analogues α-methyl-5-HT (2-Me-5-HT), 2-methyl-5-HT (2-Me-5-HT), and 5-methoxytryptamine (5-MeOT). 5-HT as well as its analogues induced concentration-related contractions, at low concentrations preceded by relaxations. The 5-HT concentration-contractile response curve was biphasic whilst the curves to α-Me-5-HT, 2-Me-5-HT, and 5-MeOT were monophasic. Tetrodotoxin (TTX) abolished the relaxations, and it inhibited the contractions to all agonists. In the presence of TTX, blockade of either 5-HT2 (ketanserin) or 5-HT3 receptors (ondansetron, tropisetron) reduced the contractions to 5-HT, whereas blockade of both 5-HT receptor types at the same time abolished them. In the absence of TTX, the contractions to 5-HT were inhibited by antagonists at 5-HT2 (ketanserin), 5-HT3 (granisetron, nanomolar concentration of tropisetron) and also 5-HT4 receptors (micromolar concentration of tropisetron). Contractions to α-Me-5-HT did not seem to be sensitive to 5-HT2 receptor blockage with ketanserin, but in the presence of TTX the contractions were abolished by the 5-HT2 receptor antagonist. The 5-HT3 receptor antagonist granisetron abolished contractions to 2-Me-5-HT. In the presence of TTX, the 5-HT2 receptor antagonist ketanserin abolished contractions to 5-MeOT, and in the absence of TTX the contractions to 5-MeOT were highly sensitive blockade of 5-HT4 receptors with tropisetron. Blockage of either 5-HT1 (methiothepin), 5-HT2 (ketanserin), 5-HT3 (ondansetron, granisetron, tropisetron) or 5-HT4 (tropisetron) receptors did not abolish the relaxations to 5-HT or 5-MeOT. In conclusion, 5-HT induces contractions of the longitudinal muscle of the guinea-pig proximal colon, through the stimulation of 5-HT2 receptors on the smooth muscle cells and 5-HT3 receptors and putative neuronal 5-HT4 receptors. 5-HT evokes relaxations via an unknown neuronal receptor.

Aims: Although probiotic prophylaxis has been suggested to prevent small bowel bacterial overgrowth, bacterial translocation and infection of pancreatic necrosis in severe acute pancreatitis, limited data are available on their antimicrobial activity. Methods and Results: Using the well-diffusion method, we studied the antimicrobial properties of a multispecies probiotic product (Ecologic 641) against a collection of pathogens cultured from infected pancreatic necrosis. All individual probiotic strains included in the multispecies preparation were able to inhibit the growth of the pathogens to some extent. However, the combination of the individual strains (i.e. the multispecies preparation) was able to inhibit all pathogenic isolates. Probiotic-free supernatants adjusted to pH 7 were not able to inhibit pathogen growth. Conclusion: Ecologic 641 is capable of inhibiting growth of a wide variety of pathogens isolated from infected pancreatic necrosis. The antimicrobial properties are to a large extent explained by the production of organic acids. Significance and Impact of the Study: Ecologic 641 is currently being used in a Dutch nationwide double-blind, placebo-controlled, randomized multicentre trial in patients with predicted severe acute pancreatitis (PROPATRIA, ISRCTN38327949).

Background Mortality during severe acute pancreatitis generally occurs early or late. Early mortality occurs as a consequence of fulminant systemic inflammation, whereas late mortality can be attributed to secondary infection of necrotic pancreatic tissue. Aims of this study were to correlate plasma levels of various cytokines and chemokines to outcome, and secondly, to assess the effect of probiotic modulation of intestinal flora on systemic cytokine levels. Materials and methods Pancreatitis was induced in rats by intraductal infusion of bile salt followed by i.v. cerulein hyperstimulation. Rats were administered a mixture of 6 probiotic strains ( Ecologic ® 641) or placebo for five days prior to and seven days after induction of pancreatitis. Plasma cytokine levels were determined before, and 6 hours, 24 hours and 7 days after induction of pancreatitis. Total bacterial counts were performed by cultivation as well as by cultivation-independent rt-PCR in pancreatic necrosis at day 7.

Infection of pancreatic necrosis with intestinal flora is accepted to be a main predictor of outcome during severe acute pancreatitis. Bacterial translocation is the process whereby luminal bacteria migrate to extraintestinal sites. Animal models were proven indispensable in detecting three major aspects of bacterial translocation: small bowel bacterial overgrowth, mucosal barrier failure, and disturbed immune responses. Despite the progress made in the knowledge of bacterial translocation, the exact mechanism, origin and route of bacteria, and the optimal prophylactic and treatment strategies remain unclear. Methodological restrictions of animal models are likely to be the cause of this uncertainty. A literature review of animal models used to study bacterial translocation during acute pancreatitis demonstrates that many experimental techniques per se interfere with intestinal flora, mucosal barrier function, or immune response. Interference with these major aspects of bacterial translocation complicates interpretation of study results. This paper addresses these and other issues of animal models most frequently used to study bacterial translocation during acute pancreatitis.

Background & aims Although the potential for probiotics is investigated in an increasing variety of diseases, there is little or no consensus regarding the desired probiotic properties for a particular disease in question, nor about the final design of the probiotic. Specific strain selection procedures were undertaken to design a disease-specific multispecies probiotic. Methods From a strain collection of 69 different lactic acid bacteria a primary selection was made of 14 strains belonging to different species showing superior survival in a simulated gastrointestinal environment. Functional tests like antimicrobial activity against a range of clinical isolates and cytokine inducing capacity in cultured human peripheral blood mononuclear cells were used to further identify potential strains. Results Specific strains inhibited growth of clinical isolates whereas others superiorly induced the anti-inflammatory cytokine IL-10. Based on functional tests and general criteria regarding probiotic design and safety, a selection of the following six strains was made (Ecologic 641); Bifidobacterium bifidum, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus salivarius and Lactococcus lactis. Combination of these strains resulted in a wider antimicrobial spectrum, superior induction of IL-10 and silencing of pro-inflammatory cytokines as compared to the individual components. Conclusions Application of strict criteria during the design of a disease-specific probiotic prior to implementation in clinical trials may provide a rational basis for use of probiotics.

The pathophysiology of parenteral nutrition–associated cholestasis (PNAC) in young children is poorly understood. The composition of the total parenteral nutrition (TPN) is reported to be of importance for the occurrence of PNAC. In this study, the effects of parenteral nutrition with different caloric loads and different amounts of lipids were studied in a rat model for PNAC. Four different groups of male Wistar rats were used. In 3 groups, a central catheter was placed in the right jugular vein. The first group (group A) received NaCl 0.9% and had free access to food and water; the other two (groups C and D) received TPN, containing 1142 and 1611 J kg −1 d −1 , respectively. In group B, the common bile duct was ligated. Animals were killed after 7 or 14 days; at these points, liver enzymes were measured, and liver histology was assessed. In the bile duct ligation group, all liver enzymes significantly increased compared with baseline. Liver enzymes did not significantly change in the other groups. Histology showed cholestatic changes in the bile duct ligation group. In the parenteral nutrition groups, significant steatotic changes were found, and in the high caloric TPN group, more so than in the TPN group. In this study, TPN was not associated with abnormal liver function tests or with histological evidence of cholestasis. Total parenteral nutrition was associated with steatosis in this rat model, which is a finding commonly reported in the literature. Therefore, it is questionable whether the rat is a good model for TPN-associated cholestasis.

Patients with functional gastrointestinal disorders often demonstrate abnormal visceral sensation. Currently, rectal sensation is assessed by manual balloon distension or barostat. However, neither test is adaptable for use in the neurophysiological characterization of visceral afferent pathways by sensory evoked potentials. The aim of this study was to assess the reproducibility and quality of sensation evoked by electrical stimulation (ES) and rapid balloon distension (RBD) in the anorectum and to apply the optimum stimulus to examine the visceral afferent pathway with rectal evoked potentials. Healthy subjects ( n = 8, median age 33 yr) were studied on three separate occasions. Variability, tolerance, and stimulus characteristics were assessed with each technique. Overall ES consistently invoked pain and was chosen for measuring rectal evoked potential whereas RBD in all cases induced the strong urge to defecate. Rectal intraclass correlation coefficient (ICC) for ES and RBD (0.82 and 0.72, respectively) demonstrated good reproducibility at pain/maximum tolerated volume but not at sensory threshold. Only sphincter ICC for ES at pain showed acceptable between-study reproducibility (ICC 0.79). Within studies ICC was good (>0.6) for anorectal ES and RBD at both levels of sensation. All subjects reported significantly more unpleasantness during RBD than ES ( P < 0.01). This study demonstrates that ES and RBD are similarly reproducible. However, the sensations experienced with each technique differed markedly, probably reflecting differences in peripheral and/or central processing of the sensory input. This is of relevance in interpreting findings of neuroimaging studies of anorectal sensation and may provide insight into the physiological characteristics of visceral afferent pathways in health and disease.

This study comprises assessment of autonomic function in irritable bowel syndrome (IBS) patients, focusing on meal-related changes. In 18 IBS patients (4 males, mean age 45+/-3.0 [SEM] years) and 19 healthy volunteers (6 males, mean age 41+/-3.5 years) blood pressure, heart rate, heart rate variability and muscle sympathetic nerve activity (MSNA) were assessed before, during and after consumption of a standardized meal. In pre- and postprandial phase Valsalva maneuver, cold pressor test (CPT) and deep breathing test were carried out and Visual Analog Scale (VAS) scores for nausea, bloating and pain were obtained. In the IBS group, the meal induced significantly higher VAS scores for pain (P=0.002) and bloating (P=0.02). During food intake, the increase in blood pressure, heart rate and MSNA was equal in patients and controls, but the increase of LF/HF ratio of heart rate variability was significantly higher in the IBS group (median [quartiles] 2.29 [1.14-3.00] versus 0.77 [0.25-1.81]; P=0.03). IBS patients scored lower on pre- and postprandial RRmax/RRmin ratio during deep breathing (DB ratio, P=0.03). The increase in MSNA (burst frequency) in response to CPT tended to be higher in the IBS patients (P=0.07). We conclude that reactivity to food intake, measured as muscle sympathetic nerve activity, is normal in IBS patients. The lower DB ratio and higher LF/HF ratio during food intake in IBS patients is an indication of a reduced parasympathetic reactivity. These results suggest that reduced baseline activity as well as responsiveness of the parasympathetic system could play a role in the pathogenesis of IBS.

An abnormality in transit is commonly considered to account for unexplained gastrointestinal (GI) symptoms. Since the symptoms of delayed transit overlap with those of accelerated transit, direct measurement of GI transit is needed to establish an accurate diagnosis. Similarly, since symptoms originating from one part of the gut may overlap with symptoms from another, localizing transit abnormality to one organ vs. another using direct measurement is an important part of diagnostic evaluations. Consequently, noninvasive tests of GI transit should be done early in the evaluation to guide therapy. We now have tools to measure transit accurately; results of transit tests often depend on the conditions selected for the test, so test results will match clinical expectations most closely when test conditions are selected to reproduce the circumstances for symptom production. This review describes the most commonly used methods for the measurement of GI transit including the gastric emptying test for some dyspeptic symptoms, small bowel transit test for dyspeptic symptoms and diarrhea, colonic transit test for constipation, and factors that influence the result of these studies. As we make progress in our understanding of the pathophysiology of transit disorders, the clinical usefulness of these diagnostic tests will be further enhanced.

OBJECTIVE: It is not well known whether physical activity (PA) is useful in the management of patients complaining of constipation. The aim of this study was to test the influence of regular PA on colonic transit time and defecation in middle-aged inactive patients suffering from chronic idiopathic constipation. MATERIAL AND METHODS: Forty-three subjects (> 45 years) were randomly divided into group A (n = 18, 16 F, 2 M) and group B (n = 25, 20 F, 5 M). Group A subjects maintained their normal lifestyle during 12 weeks, followed by a 12-week PA programme. Group B performed a 12-week PA programme after randomization. PA comprised 30 min of brisk walking and a daily 11-min home-based programme. Both groups received dietary advice. Colonic transit time was measured using a radiographic multiple marker single film technique. RESULTS: Despite dietary advice, mean fibre and fluid intake did not change. In group B a significant reduction in 3 out of 4 of the Rome I criteria for constipation was observed, i.e. percentage of incomplete defecations, percentage of defecations requiring straining and percentage of hard stools (p < 0.05). As a consequence, the number of fulfilled Rome criteria for constipation decreased (2.7 to 1.7; p < 0.05). Furthermore, the rectosigmoid and total colonic transit time decreased (17.5 to 9.6 h and 79.2 to 58.4 h, respectively; p < 0.05). After PA the number of fulfilled Rome criteria also decreased in group A (2.6 to 1.7; p < 0.05). CONCLUSIONS: In middle-aged inactive subjects with symptoms of chronic constipation, it is advisable to promote regular physical activity since it improves both the defecation pattern and rectosigmoid or total colonic transit time

Infectious complications in surgical patients often originate from the intestinal microflora. In the critically ill patient, small bowel motility is disturbed, leading to bacterial overgrowth and subsequent bacterial translocation due to dysfunction of the gut mucosal barrier. The optimal prophylactic strategy should act on all these factors, but such a strategy is not yet available. For several decades, antibiotic prophylaxis to prevent translocation of pathogenic bacteria has been studied with conflicting results. Selective decontamination of the digestive tract has shown good results, but fear for bacterial multiresistance has prevented worldwide implementation. In recent years, probiotics, living bacteria with a potential beneficial effect to their host, have shown promising results in several randomized placebo-controlled trials. Currently, in vitro and experimental research focuses on the effects of probiotics on the microflora responsible for gut-derived infections, structural mucosal barrier function and the immune system.

Stretching the stomach wall in young healthy subjects causes an increase in muscle sympathetic nerve activity and in blood pressure, the gastrovascular reflex. We compared healthy elderly subjects with healthy young subjects to find out whether the gastrovascular reflex attenuates in normal ageing and we studied whether there was a difference in autonomic function or gastric compliance that could explain this possible attenuation. Muscle sympathetic nerve activity, finger blood pressure and heart rate were continuously recorded during stepwise isobaric gastric distension using a barostat in eight healthy young (6 men and 2 women, 27 ± 3.2 years, mean ±s.e.m.) and eight healthy elderly subjects (7 men and 1 woman, 76 ± 1.5 years). Changes in cardiac output and total peripheral arterial resistance were calculated from the blood pressure signal. The baseline mean arterial pressure and muscle sympathetic nerve activity were higher in the elderly group (both P < 0.05) and muscle sympathetic nerve activity increase during the cold pressor test was lower in the elderly group (P = 0.005). During stepwise gastric distension, the elderly subjects showed an attenuated increase in muscle sympathetic nerve activity compared to the young subjects (P < 0.01). The older group tended to show a higher increase in mean arterial pressure (P = 0.08), heart rate (P = 0.06) and total peripheral arterial resistance (P = 0.09) The cardiac output rose slightly in both groups without significant difference between groups. The fundic compliance did not differ between groups. We conclude that stepwise gastric distension caused an increase in muscle sympathetic nerve activity in both groups, but the increase in the elderly was attenuated.

Background: Ileo-neorectal anastomosis (INRA), an alternative restorative procedure, was developed to reduce the pouch-related complication rate with an (at least) equal functional result. Methods: For this surgical outcome, data of all INRA patients, including bowel function and complications, were prospectively recorded. The reservoir capacity was determined repeatedly by physiologic tests. The anal sphincter complex was assessed by manometry and ultrasound examination. Evaluation of the neorectal mucosa was performed by endoscopy. Results: An INRA procedure was carried out in 39/53 selected patients (47 ulcerative colitis and 6 familial adenomatous polyposis). Fourteen UC cases were converted to ileal pouch anal anastomosis or proctectomy only, because of impossibility to completely remove the rectal mucosa or short of length of the rectal stump. The median operation time for INRA was 323 min (range 240–518), with 1,400 ml blood loss (400–4,500). The reservoirs were permanently defunctioned in 2 patients – one because of reclassification into Crohn’s disease, and one with pouchitis refractory to medical treatment. In 18 out of 37 cases, web-like stenoses occurred at the mucosa-anal level, which were treated by single (9) or repeated (5) dilatation or surgical stenoplasty (2). No pouch-related complications like pelvic sepsis, fistula or sexual dysfunction occurred. Thirteen patients had episodes of ‘pouchitis’, successfully treated with antibiotics, and 7 other cases, with functioning reservoirs, also had proximal ‘non-specific’ (i.e. no histological criteria of Crohn’s disease found) small bowel inflammation. The median bowel frequency decreased from 15×/24 h initially to 7×/24 h at 2 years. Continence was perfect in 24/37 cases. Twelve out of 37 cases had occasional nocturnal soiling and passive nocturnal fecal incontinence was reported by 2/37 patients. The neorectal compliance volume recovered from 12.5 ml kPa after subtotal colectomy and 11 ml/kPa at 6 months after INRA to a neorectal compliance of 24 ml/kPa at 2 years’ follow-up (p < 0.002; Wilcoxon signed rank test). Conclusion: The INRA procedure shows a low complication rate and reasonable functional results, there was however a considerable conversion rate in these first 53 cases and a high incidence of reclassification to CD.

OBJECTIVE: To determine the effects of hyperdynamic endotoxemia on the motility of the small intestine. SUMMARY BACKGROUND DATA: Motility disorders of the gastrointestinal tract are a common complication of sepsis. It has been suggested that gram-negative endotoxin plays a role in the pathogenesis of the accompanying diarrhea frequently observed. METHODS: Pigs were infused with lipopolysaccharide for a 24-hour period. During this fasting period jejunal motility was measured using ambulatory manometry. One and 4 days after cessation of endotoxin, pigs were enterally fed, and again motility was recorded. RESULTS: Hyperdynamic endotoxemia was achieved in this model. Manometric pressure recordings revealed that endotoxin infusion accelerated the migrating motor complex (MMC) migration along the jejunum. Also, a simultaneous increase in MMC cycling frequency was observed in the endotoxin-treated group. Elevated MMC migration velocity and cycling frequency were maintained the following day after endotoxin during feeding and returned to basal values 4 days after endotoxin. CONCLUSIONS: A small dose of continuously infused endotoxin significantly provokes jejunal motility disturbances that may contribute to diarrhea.

OBJECTIVES: In previous manometric studies, we observed that micturition was associated with phase III of the migrating motor complex. The present study aimed to objectify this possible relationship and to examine whether modulation of micturition frequency influences migrating motor complex phase III incidence. METHODS: In a retrospective study, ambulatory antroduodenal manometry and micturition data of 27 subjects were analyzed. In a prospective study, antroduodenal motility and micturition patterns were studied in five subjects who were subjected to an oral water load. Volunteers were either allowed to micturate ad libitum or instructed to postpone micturition. RESULTS: In the retrospective part of the study, a statistically significant association was found between phase III and micturition. Of all micturitions, 50% took place during or within 10 min from phase III. Also, in the prospective part of the study, phase III and micturition, as well as micturition urge, showed a significant association (p < 0.05). CONCLUSION: Micturition and phase III of the migrating motor complex are associated in time

Differential effects of motilin on interdigestive motility of the human gastric antrum, pylorus, small intestine and gallbladder.Luiking YC, Akkermans LM, van der Reijden AC, Peeters TL, van Berge-Henegouwen GP.Gastrointestinal Research Unit, Department of Surgery, University Medical Centre Utrecht, The Netherlands. yc.luiking@ah.unimaas.nlMotilin was infused in this study with the aim of examining refractory characteristics for motilin stimulation of antral phase III and fasting gallbladder emptying. Moreover, interdigestive pyloric and small intestinal motility from duodenum to ileum were studied, as these may be target organs for motilin. Eight fasting, healthy male volunteers received, on separate subsequent days, repeated infusions of 13leucine-motilin (8 pmol (kg min)(-1) for 5 min) or saline at 30 min after phase IIIs in the duodenum. Interdigestive motility of the antrum, pylorus, duodenum, jejunum and ileum was measured for maximum 10 h by using a 21-lumen perfused catheter. Gallbladder motility was measured by ultrasonography. Motilin infusions induced antral phase IIIs, but only after a preceding phase III of duodenal origin. Under this condition, time-interval to phase III at the duodenal recording site was 30 +/- 13 (SEM) min after motilin, compared with 79 +/- 14 min after saline (P < 0.01), and compared with 121 +/- 13 min for motilin infusion following an antral phase III (P < 0.001). Motilin did not affect small intestinal motility or isolated pyloric pressure waves (IPPWs). However, the number of IPPWs was significantly affected by the origin of the preceding phase III, irrespective of whether motilin or saline was infused. Gallbladder volume decreased significantly within 10 min after each motilin infusion. We conclude that this study clearly demonstrates differential regional effects of motilin. Motilin initiates antral phase IIIs, but stimulation is subject to a refractory period which is clearly prolonged after a preceding antral phase III. Motilin induced gallbladder emptying, however, is not subject to a refractory state. Small intestinal phase IIIs as well as pyloric IPPWs are not affected by motilin.

The purpose of this study was to develop a computer program for fully automated analysis of all presently known motor patterns in human colonic motility recordings. Colonic pressure recordings obtained from 24 healthy volunteers were used. Algorithms were developed for the detection and numerical analysis of five types of pressure waves: antegrade, retrograde, simultaneous, high-amplitude and isolated pressure waves. Furthermore, periodical motor activity was quantified. Validation was performed by comparison with visual analysis by two experienced observers. Patterns recorded during day- and night-time were compared using multiple-factor analysis of variance with Bonferroni correction. Automated analysis correlated well with visual peak detection (r = 0.98, P

OBJECTIVE To examine the effect of a sports drink during strenuous exercise on duodenal motility and gastrointestinal symptoms. METHODS In a cross-over design, seven male triathletes performed two 170-min run-bike-run tests at about 70% peak oxygen uptake (O(2peak)), with either a 7% carbohydrate (CHO) sports drink or tap water. Antroduodenal motility (phase III of the migrating motor complex; MMC) was measured with an ambulant manometry system. The effect of the two exercise trials on the first appearance of the MMC was assessed in the postprandial period. RESULTS Exercise heart rate, percentage O(2peak) and loss of body mass did not differ significantly between the two trials. After the start of the exercise, the expected time before the first phase III occurrence, based on the actual energy intake of the last meal in the morning before exercise (1048 +/- 294 kcal), a fixed gastric emptying rate and a lag phase for solid food, was 183 +/- 113 min (mean +/- standard deviation [SD]). The real time period between the start of the exercise with CHO and the first phase III was 63 +/- 61 min, which was significantly shorter than that observed with tap water (152 +/- 59 min). Both real time periods were shorter than the expected time period of 183 +/- 113 min (P < 0.05). During exercise, the number of subjects with a phase III was higher with CHO than with tap water (n =6 v. n =1; P < 0.05). Also, the median number of phases III per hour with CHO was higher than with tap water (0.4 v. 0.0; P < 0.05). During cycling, significantly more phases III per hour (0.9) were measured than during running (0.2). All subjects reported one or more gastrointestinal symptoms during exercise, however, without a clear association with the mode of exercise or supplementation. CONCLUSIONS Prolonged exercise results in gastrointestinal symptoms and a significant interruption of postprandial motility. Only the latter phenomenon depends on the mode of exercise and supplementation.

Background & Aims: The highly prevalent functional gastrointestinal disorders involve visceral pain and disturbed bowel habit and are associated with preceding stressful experiences, although causality and biological mechanisms remain unclear. The aim of the present study was to establish whether stress can directly and lastingly alter central nervous system responsivity to colonic distention in the rat as well as which neural pathways are likely to be involved. Methods: Rats were treated with a brief session of stressful foot shocks known to induce long-term behavioral and autonomic sensitization. Two weeks later, after induction of inhalation anesthesia, a balloon catheter was inserted in the distal colon and repeatedly inflated with brief, constant-pressure air pulses. Results: Reflex decreases in blood pressure and heart rate indicative of visceral afferent activation were greater in previously shocked rats than in controls. Colonic distention increased the expression of Fos, a marker of neuronal activation, in the sacral spinal cord and caudal brain stem. In the central amygdala and several cortical areas (prelimbic, infralimbic, agranular insular, cingulate), previously shocked rats showed reduced Fos expression following colonic distention compared with relevant controls. Conclusions: The results indicate that a brief but intense stressful experience causes long-lasting alterations in higher-order central nervous system responsivity to colonic distention even in the absence of conscious affective responses, pointing to basic alterations in the neural pathways involved. GASTROENTEROLOGY 2002;123:1216-1225

A plasma motilin peak and a partial gallbladder emptying precede the antral phase III of the migrating motor complex (MMC). To clarify the causal relationship between these factors, we aimed to study the role of motilin in interdigestive gastrointestinal and gallbladder motility simultaneously. In addition, involvement of 5HT3 receptors in the action of motilin was studied. Eight fasting, healthy male volunteers received 13Leu-motilin or 0.9% NaCl i.v. for 30 min, in randomized order on two separate occasions, from 30 min after phase III. Seven of the eight subjects also received the 5HT3 receptor antagonist ondansetron in addition to motilin, on a third occasion. Antroduodenal motility, gallbladder volumes and plasma motilin were measured. The interval between the start of infusion and phase III was 95.0 (57.6-155.7) min for saline, 28.7 (21.0-33.2) min for motilin, and 39.3 (30.7-100.5) min for motilin + ondansetron (P < 0.05). Gallbladder volume decreased by one-third from 10 min after both motilin and motilin + ondansetron infusion (P < 0.05), and returned to baseline with duodenal passage of phase III. In two of the seven subjects phase III was absent after motilin + ondansetron, although gallbladder volume decreased and only refilled during a later spontaneous phase III. We conclude that motilin induces both partial gallbladder emptying and antral phase III. Indeed, although gallbladder emptying clearly precedes antral phase III, ondansetron only prevented phase III in some cases and had no effect on gallbladder emptying. Passage of phase III in the duodenum makes an important contribution to gallbladder refilling.

Background: Prucalopride is a selective and specific 5-hydroxytryptamine4 receptor agonist that is known to increase stool frequency and to accelerate colonic transit. Aim: To investigate the effect of prucalopride on high-amplitude propagated contractions and segmental pressure waves in healthy volunteers. Methods: After 1 week of dosing (prucalopride or placebo in a double-blind, randomized, crossover fashion), colonic pressures were recorded in 10 healthy subjects using a solid-state pressure catheter with six sensors spaced 10 cm apart. Subjects kept diary records of their bowel habits (frequency, consistency and straining). High-amplitude propagated contractions were analysed visually, comparing their total numbers and using 10-min time windows. Segmental pressure waves were analysed using computer algorithms, quantifying the incidence, amplitude, duration and area under the curve of all detected peaks. Results: When taking prucalopride, stool frequency increased, consistency decreased and subjects strained less. Prucalopride just failed to increase the total number of high-amplitude propagated contractions (P=0.055). The number of 10-min time windows containing high-amplitude propagated contractions was increased by prucalopride (P=0.019). Prucalopride increased the area under the curve per 24 h (P=0.026). Conclusions: The 5-hydroxytryptamine4 receptor agonist prucalopride stimulates high-amplitude propagated contractions and increases segmental contractions, which is likely to be the underlying mechanism of its effect on bowel habits in healthy volunteers.

Objective To study the effect of Nissen fundoplication on the pattern of gastric emptying and intragastric distribution of symptoms in patients with normal and delayed gastric emptying before surgery, especially in those with delayed emptying before surgery. Background Data Gastroesophageal reflux disease is associated with delayed gastric emptying and dyspeptic symptoms in approximately 40% of the patients. After Nissen fundoplication, dyspeptic symptoms are also not uncommon. Methods Thirty-six patients (26 men, 10 women, mean age 43.1) were studied before and 3 months after Nissen fundoplication. Gastric emptying (dual-isotope, expressed in lag phase, emptying rate, T 50 , and intragastric distribution) was not included in the decision for surgery. Reflux-related and dyspeptic symptoms were scored before and at 3, 6, and 12 months after surgery. Results Twenty-six patients had normal and 10 had delayed gastric emptying before surgery. Nissen fundoplication on average enhanced gastric emptying for solids in both subgroups by a combination of a decrease in mean lag phase, emptying rate, and T 50 . The preoperative difference in intragastric distribution between patients with and without delayed gastric emptying was abolished by fundoplication. Patients with normal gastric emptying before surgery showed an increase in early postprandial satiety; in those with delayed emptying, this was not observed. A correlation was found between preoperative T 50 for liquid gastric emptying and postoperative nausea at 3 months in patients with normal gastric emptying. In patients with delayed emptying, preoperative correlations between lag phase for liquids and nausea respectively early satiety were significant, as well as for T 50 for liquids and vomiting. Conclusions Nissen fundoplication equalizes the preoperative difference in intragastric distribution and accelerates gastric emptying without an effect on symptoms in patients with preexisting delayed gastric emptying, but with an increase in early satiety in patients with normal gastric emptying. Delayed gastric emptying is not a contraindication for antireflux surgery.

INTRODUCTIONTo reduce pouch related complications after restorative proctocolectomy, an alternative procedure was developed, the ileo neo-rectal anastomosis (INRA). This technique consists of rectal mucosa replacement by ileal mucosa and straight ileorectal anastomosis. Our study provides a detailed description of the functional results after INRA.PATIENTS AND METHODSEleven patients underwent an INRA procedure with a temporary ileostomy. Anorectal function tests were performed two months prior to and six and 12 months after closure of the ileostomy and comprised: anal manometry, ultrasound examination, rectal balloon distension, and transmucosal electrical nerve stimulation (TENS). Function was subsequently related to the histopathology of rectal biopsy samples.RESULTSMedian stool frequency decreased from 15/24 hours (10–25) to 6/24 hours (4–11) at one year. All patients reported full continence. Anal sensibility, and resting and squeeze pressures did not change after INRA. Rectal compliance decreased (2.1 (0.7–2.8) v 1.5 (0.4–2.2) and 1.4 (0.8–3.7) ml/mm Hg (p=0.03)) but the maximum tolerated volume increased (70 (50–118) v96 (39–176) (NS) and 122 (56–185) ml (p=0.03)). Decreasing rectal sensitivity was found: the maximum tolerated pressure increased (14 (8–24) v 22 (8–34) (NS) and 26 (14–40) (p=0.02)) and the rectal threshold for TENS displayed a similar tendency. All patients displayed a low grade chronic inflammatory infiltrate in neorectal biopsy samples before closure of the ileostomy, with no change during follow up.CONCLUSIONSThe technique of INRA provides a safe alternative for restorative surgery. Stool frequency after INRA improves with time and seems to be related to decreasing sensitivity and not to histopathological changes in the neorectum. Furthermore, after the INRA procedure, all patients reported full continence.

Objective The keystones of surgical treatment of ulcerative colitis and familial adenomatous polyposis are resection of the diseased colon with either an ileostomy or restoration of oro-anal continuity with an ileo-anal pouch. The ileo pouch anal anastomosis however, has a 15–35% pouch-related complication rate, 10% failure rate and is accompanied by an unpredictable functional outcome. In order to reduce these unfavourable rates and to improve functional results an alternative surgical technique, the ileo neorectal anastomosis (INRA), was developed experimentally. Materials and methods In an experimental study 12 Yorkshire-Dutch landpigs had a subtotal colectomy and rectal mucosectomy. Subsequently a vascularized ileal mucosa sling was created and transposed on to the denuded rectal muscular cuff in eight. In another four animals a non-vascularized mucosa sling was transposed. The covering ileostomy was closed after 3 weeks. Repeated endoscopies, histological examinations of mucosal biopsies and rectal compliance measurements were carried out to evaluate the functional result of the neorectum. Results The surgical procedure of the INRA was technically successful in this animal study. Repeated endoscopy and histology showed complete ileal mucosa ingrowth in the neorectum without severe fibrosis in the group of animals with a vascularized sling. At follow up after 1 year no colonic metaplasia had occurred. Measurements of the neorectal reservoirs in the group of animals with a vascularized INRA procedure showed a median ‘maximum tolerated volume’ of 338 ml (range 300–410 ml). Conclusion The INRA is technically feasible and reproducible. The histologically proven survival of the vascularized ileal mucosa and development of a compliant neorectal reservoir make the INRA an interesting alternative restorative procedure. Avoidance of the pouch-related complications of the ileo pouch anal anastomosis by this procedure might herald a new era of restorative surgery.

This review describes the current state of knowledge on the hazards of exercise and the potential benefits of physical activity on the gastrointestinal tract. In particular, acute strenuous exercise may provoke gastrointestinal symptoms such as heartburn or diarrhoea. A substantial part (20-50%) of endurance athletes are hampered by these symptoms which may deter them from participation in training and competitive events. Nevertheless, these acute symptoms are transient and do not hamper the athlete's health in the long term. The only exception is repeated gastrointestinal bleeding during training and competition, which in the long term may occasionally lead to iron deficiency and anaemia. In contrast, repetitive exercise periods at a relatively low intensity may have protective effects on the gastrointestinal tract. There is strong evidence that physical activity reduces the risk of colon cancer by up to 50%. Less convincing evidence exists for cholelithiasis and constipation. Physical activity may reduce the risk of diverticulosis, gastrointestinal haemorrhage, and inflammatory bowel disease although this cannot be substantiated firmly. Up to now, underlying mechanisms are poorly understood although decreased gastrointestinal blood flow, neuro-immuno-endocrine alterations, increased gastrointestinal motility, and mechanical bouncing during exercise are postulated. Future research on exercise associated digestive processes should give more insight into the relationship between physical activity and the function of the gastrointestinal tract.

The role of interdigestive gallbladder emptying in gallstone formation is unknown. In fasting healthy subjects, gallbladder emptying is associated with antral phase III of the migrating motor complex (MMC) and high plasma motilin. Therefore, gallbladder volumes and motilin levels were measured during 13 MMC cycles in 10 cholesterol gallstone patients and compared with 20 MMC cycles in 10 healthy subjects. MMC cycle length was longer in gallstone patients than in healthy subjects (158.2 ± 17.0 vs 105.5 ± 10.4 min, respectively; P < 0.05), due to longer phase I (39.8 ± 5.7 vs 17.2 ± 3.7 min, respectively; P < 0.05). In contrast to healthy subjects, gallstone patients had no significant fluctuations of gallbladder volume during the MMC cycle, and motilin concentrations were not different in MMC cycles with phase III originating in antrum or duodenum. During MMC cycles with phase III originating in the duodenum, motilin levels were twice as high in gallstone patients as in healthy subjects (P < 0.002). In conclusion, cholesterol gallstone patients have an abnormal MMC and motilin release pattern. Their interdigestive gallbladder emptying is reduced and dissociated from the MMC. These disturbances may contribute to gallstone formation.

Background/Aims: The enterohepatic circulation of bile acids is related to normal inter-digestive gastrointestinal motility, with the gut peptide motilin also being involved. This study aimed to investigate the effect of intraduodenal artificial bile infusion on antroduodenal and gallbladder motility so as to further elucidate the controlling factors. Methods: Twelve fasting, healthy male volunteers received artificial bile (80 mol% bile acids; 15 mol% phospholipids; 5 mol% cholesterol) or placebo (saline) intraduodenally for 10 min starting 30 min after the end of phase III, according to a double-blind, randomised, cross-over design. Antroduodenal motility, gallbladder volumes, and plasma motilin levels were measured. All values are means ± SEM. Results: The interval between infusion and the subsequent phase III, as well as the origin of this phase III were not significantly different between bile and saline. Antral pressure waves were significantly more frequent during and immediately after bile infusion compared with saline infusion (p < 0.05). The duration of phase I following infusion was significantly longer after bile (24.8 ± 3.7 min) than after saline infusion (13.1 ± 1.7 min; p < 0.05). The mean gallbladder volume tended to increase in the hours following bile infusion, but to decrease after saline infusion (p = 0.06). Plasma motilin increased after bile and saline infusion in an almost identical way. Conclusion: This study provides no clear evidence for a role of intraduodenal artificial bile (i.e. its main constituents) in the regulation of migrating motor complex cycling or feedback inhibition of inter-digestive gallbladder emptying.

Objective: To develop a standardised and reproducible model of intra-abdominal infection and abscess formation in rats. Design: Experimental study. Setting: University hospital, The Netherlands. Subjects: 36 adult male Wistar rats. Interventions: In 32 rats, peritonitis was produced using two different concentrations of Escherichia coli (E. coli) and Bacteroides fragilis (B. fragilis) incorporated in fibrin clots (E. coli: 1 x 10(5) colony forming units (CFU) /ml or 1 x 10(8) CFU/ml, B. fragilis: 1 x 10(8) CFU/ml). Four rats with fibrin clots without bacteria served as uninfected controls. Main outcome measurements: Macroscopy and bacterial counts in peritoneal fluid, blood, and fibrin clots after 24 hours, 4 days, 7 days, and 4 weeks. Results: Macroscopically, there were signs of intra-abdominal infection and abscesses. With the higher starting concentration of E. coli, macroscopic signs were more pronounced and in nearly all rats bacterial counts in peritoneal fluid and fibrin clots showed persistently high numbers of E. coli and B. fragilis for at least 7 days (E. coli = 2 x 10(3) to 1 x 10(6) CFU/ml and 5 x 10(7) to 9 x 10(8) CFU/clot; B. fragilis = 1 x 10(3) to 1 x 10(6) CFU/ml and 5 x 10(7) to 6 x 10(8) CFU/clot). Conclusion: This standardised and reproducible model of intra-abdominal infection and abscess formation seems well suited for further use and development in experiments on the pathophysiology of intra-abdominal infection and abscesses.

Objective The intestinal flora is thought to play an important role in regulation of immune responses. We investigated the effects of changing the intestinal flora on the course of adjuvant-induced arthritis (AIA) and on experimental autoimmune encephalomyelitis (EAE) by the use of oral antibiotics. Methods Oral treatment with either vancomycin or vancomycin, tobramycin, and colistin was started after AIA and EAE induction. Clinical symptoms of AIA and EAE were monitored, and microbial analysis of ileal samples was performed. Results Oral vancomycin treatment after disease induction significantly decreased clinical symptoms of AIA. Simultaneously, increased concentrations of Escherichia coli were detected in the distal ileum of vancomycin-treated rats. Ileal concentrations of E coli were inversely related to disease scores in rats with AIA. Coadministration of colistin/tobramycin to prevent the increase in E coli abrogated the beneficial effect of vancomycin on AIA. Vancomycin treatment also reduced the clinical symptoms of EAE. Conclusion We propose oral vancomycin as a novel therapeutic strategy in autoimmune diseases.

Background The consumption of coffee allegedly induces or aggravates gastrointestinal symptoms. In order to investigate the effect of coffee on gastrointestinal motility we studied the effect of coffee on gastric emptying and oro-caecal transit time. Methods In a randomised, controlled, cross-over study gastric emptying and oro-caecal transit time were studied in 12 healthy volunteers, using applied potential tomography and lactulose hydrogen breath test, respectively. After 1 day of coffee abstinence and an overnight fast, coffee or the control drink (water) was drunk and 10 min thereafter a liquid nutrient meal was ingested together with lactulose. During 150 min, recordings were made with applied potential tomography and breath samples were taken every 5 min. Lag-phase duration and gastric half-emptying time were determined by two blinded observers. Results The lag-phase duration after coffee (median 19.8 min, range 6–47 min) was not significantly different from that after water (median 19.3 min, range 11–37.5), nor was the gastric half-emptying time (median 75.7 min, range 56–157.6 vs. median 83.4 min, range 64.6–148.4). Likewise, coffee had no significant effect on oro-caecal transit time (median 135 min, range 60–270 vs. median 140 min, range 55–270). No significant correlation between any of these parameters and mean daily coffee intake was found. Conclusions Coffee does not affect gastric emptying of a liquid meal or small bowel transit.

Background/Aims: Translocation of gut bacteria occurs in obstructive jaundice, the underlying mechanisms are unclear. We designed this experimental study to investigate the association between interdigestive motility and the pathogenesis of bacterial translocation during biliary obstruction. Methods: Rats were fitted with jejunal myoelectrodes for the measurement of the interdigestive migrating motor complex (MMC) and with two cannulas in the proximal common bile duct (CBD) for exteriorization of biliary flow. This allowed measurement of MMCs under control conditions with an intact enterohepatic circulation and during 3 days of CBD obstruction without surgical intervention. Mesenteric lymph nodes, liver, spleen and segments of the duodenum, the jejunum and the caecum were removed for microbial culturing. Results: The MMC cycle length increased from 17.3 min before CBD obstruction to 31.9, 34.1, and 25.3 min on days 1, 2 and 3, respectively, after CBD obstruction (p < 0.05 for all days). Bacterial levels in the jejunum were significantly higher in CBD-obstructed rats than in control rats. The translocation incidence was significantly higher in rats with CBD obstruction (6/8) than in control rats (1/8). The bacterial levels in the jejunum correlated significantly with the MMC cycle length (r = 0.60, p Conclusion: Experimental biliary obstruction is associated with disturbance of MMCs, small-bowel bacterial overgrowth and increased bacterial translocation.

Functional bowel disorders are more prevalent in women than in men, but the reason for this is unclear. Stressful experiences can increase the risk for or precipitate intestinal dysfunction. Using a model for long-term stress-induced sensitisation in rats, it was investigated whether male and female rats differ in susceptibility for long-term colonic, behavioural and hormonal disturbances following brief but intense stress. Male and female Wistar rats were fitted with chronic electrodes on proximal colon and given either a 15-minute session of foot shocks or no shocks. Two weeks later, rats were exposed to two different novel stressful challenges in the home cage: an electrified prod (day 14) and an 85 dB noise Stressor (day 15). Digitalised colonic myoelectric spike burst activity was quantified automatically. Behaviour during prod and noise exposure was scored blindly from videotape. Resting plasma hormone concentrations at the end of the study were determined by radio-immuno assay. Following prod stress on day 14, both male and female preshocked rats showed a greater increase in colonic spike burst frequency than controls, but similar behaviour, and the dynamics of colonic motility differed between sexes. Following noise stress on day 15, only a small change in burst frequency was seen in all rats, but preshocked rats showed less self-grooming behaviour and there was a tendency for preshocked females to show increased noise-induced immobility. Preshocked rats also had lower levels of plasma free thyroxine. While both male and female rats show long-term stress-induced colonic sensitisation and hormonal changes, females show a different activation pattern of colonic motility, and may be more vulnerable for altered behavioural reactivity, following stress.

Background : Strenuous exercise exacerbates gastro-oesophageal reflux and symptoms and this may be diminished by antisecretory medication with omeprazole. Methods : Fourteen well-trained athletes (13 men, one woman), who indicated suffering from either heartburn, regurgitation or chest pain during competition running, performed two experimental trials at 2-week intervals using a randomized, double-blind, placebo-controlled crossover design. During the 6 days preceding the trial and on the trial day itself either 20 mg of omeprazole or a placebo was administered. Two hours after a low-fat breakfast and 1 h after the last study dose, the trial started with five successive 50-min periods: rest, three running periods on a treadmill, and recovery. Reflux (percentage time and number of periods oesophageal pH

Aim : To investigate the effect of the prokinetic drug, cisapride, on fasting and postprandial acid exposure in the proximal duodenum. Methods : Using a double-blind, placebo-controlled crossover study design, 12 healthy male volunteers were studied. After 1 week of dosing (cisapride 20 mg b.d. orally or placebo), fasting and postprandial antroduodenal pH-and pressure-recordings were made. Using a small-caliber (4 mm) catheter, containing one antral and two duodenal pH electrodes, and two antral and three duodenal pressure recording sites. Transmucosal potential difference was measured to ensure proper catheter position. Infusions of 0.1 N HCl were given in the duodenal bulb. Results : Endogenous acidification of the duodenal bulb occurred more frequently during phase II and post- prandially, compared to phase I (P

There is considerable evidence for a role of stressful experiences in psychosomatic disorders in humans, but the mechanisms leading to altered responsivity and the relative contributions of central and peripheral neuronal changes, however, are still under debate. To investigate the contribution of specific brain areas to sensitized responsivity, rats were exposed to a single brief session of inescapable footshocks (preshocked) or no shocks (control) in a gridcage. Two weeks later, an electrified prod was inserted in the home cage for 15 min and the behaviour recorded. One hour later rats were perfused and brain sections were stained for Fos protein immunoreactivity. The number of Fos positive neurons was quantified in 27 brain areas. No significant difference in behaviour was found between the groups during the shock prod challenge. A significantly higher number of Fos positive neurons was found in preshocked rats compared to controls in the following brain areas: agranular insular cortex, frontal cortex, nucleus accumbens, bed nucleus of the stria terminalis, basolateral amygdala, CA1 area of the hippocampus, paraventricular hypothalamic nucleus, dorsolateral central grey, locus coeruleus, nucleus of the solitary tract and lateral paragigantocellular nucleus. We conclude that altered reactivity to stressful challenges in brain areas involved in neuroendocrine and autonomic control may play a role in long-term sensitization of neuroendocrine and autonomic responses in preshocked rats under conditions where behavioural sensitization is not expressed.

The migrating motor complex (MMC) shows large variations within an individual and between individuals. This study aimed to investigate, with respect to this variability, the importance of gastric or duodenal origin of phase III activity. Interdigestive 6- to 10-h stationary antroduodenal motility recordings of 19 healthy male subjects were analyzed for MMC cycle durations and duration of phases I, II, and III, all with respect to the place of origin of each phase III. Data are given for the duodenal recording site as means ± SE. Mean MMC cycle duration was 117.3 ± 13.9 min, regardless of the place of origin of phase III. Seventy-two phase III cycles were observed in total, 35 and 37 starting in the “antrum” and duodenum, respectively. After a phase III of “antral” origin, MMC cycle duration was 156.1 ± 11.0 min, significantly longer than MMC cycle duration following a phase III of duodenal origin, 80.5 ± 10.7 min ( P < 0.001). Phase III duration was longer when of “antral” origin than when starting in the duodenum (7.6 ± 0.4 and 5.3 ± 0.4 min, respectively; P < 0.001). MMC cycle duration and duration of phases I, II, and III depend on the place of origin of phase III (“antral” or duodenal) and on the origin of the preceding phase III. This factor explains part of the MMC variability observed within individuals. Mean MMC cycle duration in healthy subjects or patients should therefore also include information on the origin of phase III.

Individual differences in behavioral and physiological response patterns to stress may contribute to vulnerability for stress-related illnesses such as functional gastrointestinal disorders. Animal models could give clues about specific individual determinants of intestinal reactivity to stress and stress-induced sensitization. Rats fitted with permanent electrodes on the proximal colon were exposed to a single session of foot shocks (10 × 6 s in 15 min, preshocked) or no shocks (control). Two weeks later, the preshocked group showed a significantly greater colonic spike burst response to a novel shock-prod stressor in the home cage than controls. The increase in burst frequency was positively correlated with the duration of active burying of the threatening prod in both experimental groups, but not with other behavioral components. Basal colonic burst frequency at rest was negatively correlated with the increase in burst frequency due to shock-prod stress in both groups, but the degree of sensitization in preshocked rats vs. controls was of similar magnitude in rats with low and high basal colonic burst frequency. The results indicate that colonic responsivity to stress is related to both basal motility status and individual coping strategies.

OBJECTIVE: To clarify the role of the migrating motor complex (MMC) in the regulation of small intestinal microflora and bacterial translocation. SUMMARY BACKGROUND DATA: The intestinal microflora may serve as a source of infectious microorganisms. Failure of regulatory mechanisms of the intestinal flora could therefore play an important role in the pathogenesis of gut-derived infections. METHODS: Rats were fitted with small intestinal myoelectrodes. MMCs were measured on a control day and 3 consecutive days during continuous administration of morphine or placebo. Mesenteric lymph nodes, liver, spleen, peripheral blood, duodenum, and ileum samples were cultured quantitatively. RESULTS: The mean MMC cycle length in placebo-treated animals was 15.1+/-0.5 minutes. MMCs were completely disrupted after morphine treatment. Total bacterial growth in the duodenum was 7.27+/-0.34 10log colony-forming units (CFU)/g with placebo and 8.28+/-0.27 CFU/g with morphine. In placebo-treated animals, the mean MMC cycle length the day before culturing correlated with total bacterial growth in the duodenum. Translocation incidences to the mesenteric lymph nodes, liver, spleen, and blood were 0/8, 1/8, 0/8, and 0/8 with placebo and 7/8, 6/8, 5/8, and 0/8 with morphine. The overall translocation incidence was 1/8 in placebo-treated animals and 8/8 in morphine-treated animals. CONCLUSIONS: The MMC is an important mechanism controlling bacterial growth in the upper small bowel. Its disruption with morphine promotes duodenal bacterial overgrowth and bacterial translocation.

Background After Nissen fundoplication patients frequently report upper abdominal (dyspeptic) symptoms. Theoretically, these symptoms may be the result of changes in function of the proximal stomach as induced by fundoplication. Methods In this case–control study the response of the proximal stomach to both distension by an air-filled bag and a liquid meal were evaluated with the use of a barostat. In 12 patients after fundoplication and 12 healthy volunteers (age- and sex-matched) perception of symptoms was evaluated during both bag distension and liquid meal stimulus. Results The minimal distending pressure required to overcome the intra-abdominal pressure was significantly different between patients and controls (mean(s.e.m.) 9·34(0·26) versus 6·73(0·43) mmHg; P < 0·001). There was no difference between groups in either the fasted state, volume–pressure curve (compliance) or total symptom score. After ingestion of the liquid meal the adaptive relaxation in the fundoplication group was significantly less than that in controls (mean(s.e.m.) 150(29·2) versus 244(34·8) ml; P = 0·04). Conclusion This study showed that after Nissen fundoplication compliance of the proximal stomach is no different from that in healthy volunteers. Postprandial relaxation of the proximal stomach is decreased and this abnormality may be involved in the pathogenesis of reported dyspeptic symptoms.