Assessment of gastric sensorimotor function in paediatric patients with unexplained dyspeptic symptoms and poor weight gain

Recent studies indicate that impaired meal accommodation or hypersensitivity to distention are highly prevalent in adult functional dyspepsia (FD). Our aim was to investigate whether similar abnormalities also occur in paediatric FD. Sixteen FD patients (15 girls, 10-16 years) were studied. The severity (0-3; 0, absent; 3, severe) of eight dyspeptic symptoms (epigastric pain, fullness, bloating, early satiety, nausea, vomiting, belching and epigastric burning) and the amount of weight loss were determined by questionnaire. All children underwent a gastric barostat study after an overnight fast to determine sensitivity to distention and meal-induced accommodation, which were compared with normal values in young adults (18-22 years). On a separate day, all patients underwent a gastric emptying breath test. A mean weight loss of 4.8 +/- 0.9 kg was present in 14 children. Compared with controls, patients had lower discomfort thresholds to gastric distention (8.8 +/- 1.0 mmHg vs 13.9 +/- 1.9 mmHg, P < 0.02) and gastric accommodation (87 +/- 25 mL vs 154 +/- 20 mL P < 0.04). Hypersensitivity to distention and impaired accommodation were present in respectively nine (56%) and 11 (69%) patients. No relationship was found between barostat and gastric emptying, which was delayed in only three patients. The majority of children with unexplained epigastric symptoms have abnormalities of gastric sensorimotor function.     

Symptom pattern and pathophysiological correlates of weight loss in tertiary-referred functional dyspepsia

Abstract  In patients with gastrointestinal symptoms, weight loss is an alarm symptom, indicative of organic disease. Recent studies reported weight loss in subsets of functional dyspepsia (FD) patients. The aim of this study was to analyse symptom patterns associated with weight loss in tertiary care FD. Six hundred and thirty-six FD patients (67% female, mean age 43 years) completed a dyspepsia questionnaire, and underwent gastric emptying and gastric barostat studies. After identifying independent symptom domains through orthogonal factor analysis, patients were clustered on the basis of symptom profile. Clusters were compared in terms of their association with weight loss and gastric emptying or sensorimotor function. Weight loss (4.2 kg on average) correlated most strongly with early satiety followed by nausea and vomiting ( ρ respectively 0.38, 0.28 and 0.23, all P  < 0.0001). Factor analysis revealed three factors: Factor 1 characterized by nausea, vomiting and early satiety; factor 2 by early satiety, postprandial fullness and bloating; and factor 3 by pain, epigastric burning and belching. Subsequent cluster analysis revealed six patient clusters. The most severe cluster, which loaded high on all three factors, and a cluster dominated factor 2 were associated with the highest average weight loss (6.8 and 8.0 kg, respectively). The former cluster was also characterized by visceral hypersensitivity and delayed gastric emptying. The lowest weight loss occurred in the two clusters that had depressed scores for both early satiety associated factors (2.4 and 2.5 kg, respectively). In tertiary care FD, weight loss is strongly associated with two early satiety associated symptom clusters.     

Dyspeptic symptoms in the general population: a factor and cluster analysis of symptom groupings

Abstract  Both dyspeptic and gastro-oesophageal reflux-like symptoms are frequent in the general population, but their degree of overlap is unknown. In severe functional dyspepsia (FD), symptoms are organized in factors associated with pathophysiological mechanisms. The aims of this study were: (i) to assess the prevalence of dyspeptic symptoms with and without overlapping reflux symptoms in the general population and their impact on daily life and on healthcare utilization; and (ii) to compare symptom groupings in the general population to FD patients. A total of 2025 subjects, representative of the Belgian general population, were used in this study. The subjects were submitted to a questionnaire with validated questions on their dyspeptic and reflux symptoms and with evaluators of impact on daily life and use of healthcare resources. Significant dyspeptic symptoms were found in 417 (20.6%). Overlapping reflux symptoms were present in 141 (33.8%). In this group, symptoms were more frequent and more severe. Dyspeptic symptoms induced weight loss (12.7%) and absenteeism (12.4%), affected daily life (61.2%) and generated use of healthcare resources, such as medical consultations (61.4%) and medication (70.9%). Factor analysis revealed a three-component structure with factor 1 including fullness, bloating and early satiety, factor 2 including nausea and vomiting and factor 3 including discomfort, pain, belching and reflux. If forced in a four-factor model, the analysis separates belching as independent factor. Dyspeptic symptoms are frequent in the general population, with overlapping reflux symptoms and increased symptom burden in about a third.     

Association between changes in symptoms and gastric emptying in gastroparetic patients treated with gastric electrical stimulation

Abstract  To investigate whether there is an association between gastric emptying rate and symptom improvement in gastroparetic patients treated with gastric electrical stimulation (GES), we retrospectively reviewed 63 gastroparetic patients who received GES therapy for at least 1 year. Patient characteristics, seven upper gastrointestinal (GI) symptoms and 4-h standardized gastric emptying test (GET) were evaluated at baseline and at 1 year of GES. All symptoms were significantly reduced ( P  <   0.001). Mean gastric retention was reduced by 7% ( P  =   0.102) for measurement at 4 h. Of the 63 patients, 14 had their GET normalized and 49 remained delayed after 1 year. Normalized GET patients had a similar symptom improvement as those whose GET remained delayed. Of all upper GI symptoms, the improvements in vomiting ( P  =   0.04), nausea ( P  =   0.002) and epigastric pain ( P  =   0.001) were significantly correlated with reduction in 4-h gastric retention between baseline and 12 months of GES therapy for patients with normalized gastric emptying but there were no correlations with any symptoms and change in gastric emptying for those patients who remained delayed. In summary, overall gastric emptying is not significantly accelerated at 4 h after successful symptomatic improvement with GES but nausea, vomiting and epigastric pain can be correlated with normalization of GET in a subset of patients.     

Lower postprandial gastric volume response in diabetic patients with vagal neuropathy

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 repsponse 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 intra-oesophageal capsaicin instillation on heartburn induction and oesophageal sensitivity in man

Abstract  Heartburn is the most typical gastro-oesophageal reflux disease (GERD) symptom. The transient receptor potential vanilloid receptor-1 (TRPV₁) is a candidate mediator of heartburn. Exposure of TRPV₁ to capsaicin is characterized by activation , followed by desensitization . Our aim was to investigate the effect of intra-oesophageal capsaicin instillation on oesophageal symptom perception ( activation ) and on sensitivity to oesophageal acid perfusion and oesophageal balloon distention ( desensitization ). In a first protocol ( n  = 10), saline or capsaicin solution were instilled in the mid-oesophagus and symptoms were rated at 5-min intervals for 60 min. In a second study ( n  = 10), oesophageal 0.1 N hydrochloric acid perfusion was performed 60 min after pretreatment with saline, low or high dose capsaicin. In a third study ( n  = 10), sensitivity to oesophageal balloon distention was determined before and at 30-min intervals up to 90 min after pretreatment with saline, low or high dose capsaicin. Areas under the curve (AUC) for symptom intensities under different conditions were calculated and compared with Kruskal–Wallis test. Oesophageal capsaicin instillation induced transient symptoms of retrosternal and epigastric burning in a dose-dependent fashion. After oesophageal capsaicin or saline instillation, there was no difference in symptom pattern and intensities induced by oesophageal acid perfusion. After oesophageal capsaicin or saline instillation, sensitivity to oesophageal balloon distention and oesophageal compliance were not significantly altered. Oesophageal instillation of the TRPV₁ receptor agonist capsaicin induces symptoms of retrosternal and epigastric burning in a dose-dependent fashion. Pretreatment with capsaicin does not desensitize the oesophagus to acid perfusion or to balloon distention.     

Impaired drinking capacity in patients with functional dyspepsia: intragastric distribution and distal stomach volume

The water drink test is a good tool to evoke dyspeptic symptoms. To what extent these symptoms are related to altered gastric distribution is not clear. Therefore, we determined gastric volumes after a drink test using SPECT. After a baseline scan 20 healthy volunteers (HV) and 18 patients with functional dyspepsia (FD) underwent a drink test (100 mL min(-1)) followed by five scans up to 2 h. Dyspeptic symptoms were scored before every scan. A Wilcoxon signed rank test (P < 0.05) and a mixed effects model were used for statistical analyses. Fasting volumes were significantly higher in FD compared to HV for total, proximal and distal stomach (P < 0.001). Functional dyspeptic patients ingested significantly less water (P < 0.001) and had an impaired filling of the distal part of the stomach (P = 0.001) after the drink test. In FD, bloating (prox. 80%, dist. 56%), pain (prox. 87%, dist. 62%) and fullness (prox. 80%, dist. 59%) were determined more by proximal stomach volume rather than distal stomach volume. These data suggest that drinking capacity is mainly determined by antral volume, with a reduced antral filling in FD compared to HV. The persisting symptoms of bloating, pain and fullness in FD are predominantly associated with proximal stomach volume.     

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.     

Gastric hypersensitivity induced by oesophageal acid infusion in healthy volunteers

Abstract  Distal oesophageal acid exposure has been shown to increase visceral sensitivity of the proximal oesophagus via central sensitization. Here we evaluated whether acidification of the distal oesophagus also affects the sensorimotor function of the proximal stomach. A gastric barostat study combined with a 30-min acid (HCl 0.15 mol L⁻¹) or saline infusion in the distal oesophagus was performed in 18 healthy volunteers. Gastric and cutaneous sensitivity was assessed before and up to 2 h after the start of infusion. Directly after acid infusion, but not after saline, the threshold for discomfort decreased (–6.4 ± 1.7 vs 0.4 ± 0.4 mmHg; P = 0.028) and distension-induced symptoms increased significantly compared with the baseline (122 ± 49% vs −3 ± 9%). Cutaneous sensitivity remained unaffected by acid infusion. In contrast, when the infused liquid was aspirated 3 cm more distally, at the level of the lower oesophageal sphincter, the effect of acid infusion on gastric sensitivity was abolished and the increase in distension-induced symptoms was reduced (61 ± 24%). Distal oesophageal acid infusion induces visceral hypersensitivity without affecting somatic sensitivity arguing against a similar mechanism of central sensitization as observed in non-cardiac chest pain. As reduction of the acid load to the stomach prevented this effect, our findings indicate that either gastric and/or duodenal acidification is involved. It should be emphasized though that aspiration from distal oesophagus may have attenuated the effect by reducing the acid-exposed area or by reducing the contact time.     

Functional dyspepsia and the Rome criteria: a success story

The Rome III criteria for functional dyspepsia (FD), published in 2006, immediately generated controversy but have arguably helped to jump start the field in terms of mechanistic and therapeutic research. One controversy has surrounded the veracity of FD symptom subgroups and their overlap. In clinical practice the overlap of postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS) is striking. In this issue, results from Belgium suggest overlap can be reduced by reclassifying those who have postprandial pain or nausea as PDS, and meal‐related symptoms predominate in FD. This is consistent with other objective experimental observations. The realization most FD occurs postmeal ingestion is driving a new conceptualization of the syndrome. For example, the observation there is an excess of duodenal eosinophils in PDS has been confirmed, with recent observations implicating increased duodenal permeability and immune activation. The link between PDS and anxiety, not identified in EPS, provides yet further evidence for distinct pathophysiological entities. While symptom‐based criteria likely need refinement, the recognition of PDS and EPS has promoted exciting progress.     

Vagal activation by sham feeding improves gastric motility in functional dyspepsia

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

Experimental oesophagitis in the rat is associated with decreased voluntary movement

Abstract  Growing interest has arisen regarding the mechanism of dyspeptic symptom generation. However, no evaluation system of these symptoms in animals has been developed. In this study, we examined whether voluntary movement of rats could be a measure to assess visceral symptoms of reflux oesophagitis. A chronic acid reflux oesophagitis model was made using rats, and the size of erosions was measured. Omeprazole was administered to the oesophagitis rats for 10 days. The amount of voluntary movement was measured by an infrared sensor. Intracellular spaces in oesophageal epithelium were also measured using a emission electron microscope. NP-40 soluble and insoluble fractions of claudins were examined by Western blot. Voluntary movement was significantly lower in the oesophagitis model rats than in the sham-operated rats ( P  <   0.01). Although omeprazole reduced the size of erosions, it did not significantly affect the total amount of voluntary movement ( r  = −0.033, P  =   0.916). Intracellular spaces were significantly dilated in the oesophagitis model rats and claudin-3 showed a significantly lower relative quantity in the NP-40 insoluble fraction. Omeprazole significantly increased voluntary movement of oesophagitis model rats and the relative quantity of claudin-3 in the insoluble fraction ( P  <   0.05). Dilated intercellular spaces and the lower level of claudin-3 may relate to the voluntary movement of oesophagitis model rats. Decreases in voluntary movement of oesophagitis model rats may reflect visceral symptoms and be able to serve as an index of chronic abdominal symptoms.     

Intestinal electrical stimulation improves delayed gastric emptying and vomiting induced by duodenal distension in dogs.

The aim of this study was to investigate the effects of short-pulse intestinal electrical stimulation (IES) on duodenal distention-induced delayed gastric emptying and vomiting in dogs and its possible mechanisms. The study was performed in 12 dogs with jejunal electrodes and a duodenal cannula in three separate experiments to investigate the effects of IES on duodenal distension (DD)-induced delayed gastric emptying and discomfort signs, vagal efferent activity, and jejunal tone. We found that: (i) IES significantly accelerated gastric emptying of liquid delayed by distension (18.05 +/- 4.06%vs. 7.18 +/- 1.99%, P = 0.036 at 60 min). (ii) IES significantly reduced vomiting and discomfort/pain induced by distension. The average signs score was 15.33 +/- 1.37 during distension which decreased to 6.50 +/- 0.91 (P = 0.0002) with IES. (iii) IES did not change vagal afferent activity, which was assessed by the spectral analysis of the heart rate variability. (iv) IES decreased jejunal tone. In conclusion, IES with parameters commonly used in gastric electrical stimulation for nausea and vomiting associated with gastroparesis improves DD-induced delayed gastric emptying and prevents DD-induced vomiting and discomfort signs. Further studies are warranted to investigate the therapeutic potential of IES for gastrointestinal symptoms associated with disturbances in motility and sensory function in small intestine.     

Gastric dysmotility following orthopaedic scoliosis surgery in patients with cerebral palsy: a case series

Scoliosis is a common complication in children with cerebral palsy (CP). In these patients, surgical correction carries a high risk of complications. CP is also associated with gastrointestinal dysmotility such as delayed gastric emptying and gastro-oesophageal reflux. We describe 5 patients with CP in whom symptoms of gastric dysmotility clearly exacerbated after orthopaedic scoliosis surgery. They all showed persisting vomiting, nausea, bloating, weight loss, and anorexia necessitating total parental nutrition and/or jejunal feeding. This intensified nutritional support resulted in weight gain. Symptoms, however, persisted in half of the patients. The aetiology of these gastro-intestinal motility problems following scoliosis surgery remains unclear. Mechanical obstruction needs to be ruled out. Delayed gastric emptying may be due to postprandial antral hypomotility as a consequence of sympathic stimulation. Malnutrition could further aggravate gastrointestinal dysmotility. This complication should be taken into account when surgery for spinal deformities in CP patients is planned, especially in patients with pre-existing gastrointestinal motility problems.     

Clinical effects of STW 5 (Iberogast®) are not based on acceleration of gastric emptying in patients with functional dyspepsia and gastroparesis

Abstract  STW 5, a herbal extract, is effective for the treatment of symptoms in patients with functional dyspepsia (FD). However, its mode of action is still unclear and a modulation of gastric motility is hypothesized. This multicentre, placebo-controlled double-blind study addressed the question of whether STW 5 accelerates gastric emptying in patients with FD and gastroparesis. One-hundred and three patients diagnosed with FD were randomly assigned to a treatment with either STW 5 or a liquid placebo for 28 days. The primary end point of the study was a change of a validated gastrointestinal symptom (GIS) score under treatment. Additionally, patients underwent a ¹³C octanoic acid breath test for the assessment of the gastric half-emptying time ( t _1/2). Patients with prolonged t _1/2 were diagnosed with gastroparesis and requested to repeat the test at the end of treatment. A change of t _1/2 was defined a secondary study end point. t _1/2 was prolonged in 48.6% of patients in the STW 5 group and in 43.8% of the placebo group. During treatment, t _1/2 increased non-significantly in patients treated with STW 5 (+23 ± 109 min; P  = 0.51) and slightly accelerated among patients in the placebo arm (−26 ± 51 min; P  = 0.77) ( P  = 0.49). The improvement of the GIS ( P  = 0.08) and the proportion of patients with a treatment response ( P  = 0.03) were more pronounced in the STW 5 group. Our findings suggest that the clinical effects of STW 5 in patients with FD and gastroparesis are not directly mediated by an acceleration of gastric emptying. A clear-cut correlation with symptom improvement is still lacking.     

A dose-ranging, placebo-controlled, pilot trial of Acotiamide in patients with functional dyspepsia

Abstract  Impaired gastric accommodation, hypersensitivity to distension and delayed gastric emptying are major pathophysiological mechanisms in functional dyspepsia (FD). Acotiamide (Z-338) was well-tolerated in healthy volunteers. To determine the effect of three doses of Acotiamide on major pathophysiological mechanisms, symptoms, quality of life (QOL) and safety in functional dyspeptics. A phase IIa, randomized, double-blind, placebo-controlled study (14, 21 and 28 days, respectively, for run-in, study drug administration and follow-up). Gastric accommodation, sensitivity to distension and gastric emptying were assessed by barostat and ¹³C breath test, symptoms by daily diary cards and QOL by SF-36. A total of 71 patients were enrolled (62 evaluable). There was no effect on gastric emptying and sensitivity to distension. 300 mg was better than placebo for meal accommodation ( P  = 0.024). 100 mg was better than placebo at week 2 for upper abdominal bloating ( P  = 0.001) and overall symptom score ( P  = 0.022), and at week 3 for bloating ( P  = 0.008) and heartburn ( P  = 0.041). 100 mg was also better than placebo for QOL (physical function) ( P  = 0.003). Acotiamide was safe and well-tolerated in patients with FD. The involved mechanism could at least in part depend on an effect on meal-induced accommodation. 100 mg Acotiamide exhibited the potential to improve FD symptoms and QOL. Further studies are indicated.     

Reproducibility and symptomatic predictors of a slow nutrient drinking test in health and in functional dyspepsia

Abstract  Impaired accommodation to a meal has been recognized as a pathophysiological mechanism in functional dyspepsia (FD). Based on observations in tertiary care patients, the drinking test has been proposed as a non-invasive tool to estimate accommodation. Our aim was to assess the reproducibility of the drinking test and its correlation with demographic, symptomatic and pathophysiological parameters in secondary care FD patients and healthy controls. Thirty-four healthy controls and 78 FD patients completed a drinking test (3 respectively 2 times), a gastric emptying study and an FD symptom questionnaire. Factors influencing maximal volume and gastric emptying were determined, and the reproducibility of the drinking test was investigated. The maximal satiety was reached at a lower volume in patients (489 ± 276 and 503 ± 248 mL for first and second test respectively vs 937 ± 428 and 1048 ± 421 mL, P  < 0.0001). The ingested amount depended on age, sex and baseline FD symptom score. Patients' sex, final satiety score, total score for stomach complaints at screening and total symptom score before test accounted for the total symptom score after the test. The slow nutrient drinking test confirms its possible role as an attractive non-invasive and reproducible tool for the diagnosis of impaired accommodation and for the assessment of treatment responsiveness.     

Visceral perceptions and gastric myoelectrical activity in healthy women and in patients with bulimia nervosa

Bulimia nervosa remains a common eating disorder in young women. Little is known about upper gastrointestinal symptoms or gastric motility in patients with bulimia nervosa. The aim of this study was to measure gastric myoelectrical activity and hunger/satiety and stomach emptiness/fullness before and after a non-nutrient water load and solid-phase gastric emptying in hospitalized patients with bulimia nervosa (n = 12) and in healthy women (n = 13). Gastric myoelectrical activity was measured by means of cutaneous electrodes; visual analogue scales were used to measure perceptions of hunger/satiety and stomach emptiness/fullness. Before and after a standard water load the bulimia patients reported significantly greater stomach fullness and satiety compared with control subjects (P < 0.01). The percentage of gastric myoelectrical power in the normal 3 cpm range was significantly less in bulimics compared with controls. Power in the 1–2 cpm bradygastria range was significantly greater in bulimia patients before and after the water load compared with the control subjects (P < 0.05). Solid-phase gastric emptying studies using radio-isotope-labelled scrambled eggs showed the lag phase was shortened in the bulimic patients (16 ± 4 min vs 31 ± 4 min in controls, P < 0.01), but the percentage of meal emptied at 2 h was similar to control values. In conclusion: bulimia patients had exaggerated perceptions of stomach fullness and satiety in response to water; and abnormal gastric myoelectrical activity and accelerated lag phase of gastric emptying were objective stomach abnormalities detected in hospitalized patients with bulimia nervosa.     

GLP-1 regulates gastroduodenal motility involving cholinergic pathways

Abstract  The gut-born incretin hormone glucagon-like peptide-1 (GLP-1) delays gastric emptying. To elucidate the mechanisms by which GLP-1 affects gastroduodenal motility and glycaemia, we studied the effects of exendin(9–39), a potent GLP-1 receptor antagonist, on gastroduodenal motility and pancreatic hormones. In this randomized, double-blind, placebo-controlled, four-arm, cross-over trial, 10 healthy volunteers were studied during the interdigestive period followed by duodenal perfusion of a mixed liquid meal (250 kcal). On four separate days, exendin(9–39), atropine, exendin(9–39) + atropine or saline were infused intravenously. Antro-pyloro-duodenal and fundic motility were assessed. The compliance of the proximal stomach was determined by isobaric distensions. During fasting, exendin(9–39) did not influence proximal gastric volume, pyloric tone, and duodenal contractility. Exendin(9–39) significantly increased antral waves only in the absence of atropine. During duodenal meal perfusion, exendin(9–39) significantly reduced proximal gastric volume accommodation, abbreviated postprandial antral inhibition, reduced the postprandial increase in pyloric tone, and reduced gastric compliance. Atropine abolished the effects of exendin(9–39) on gastric volume accommodation but did not affect its effects on postprandial antroduodenal motility and on gastric compliance. Exendin(9–39) increased fasting and postprandial glycaemia and plasma glucagon but not insulin concentrations. Atropine did not affect GLP-1 secretion. Cholinergic mechanisms mediate the effects of GLP-1 on postprandial gastric accommodation but not on antro-pyloro-duodenal motility. GLP-1 reduces fasting and postprandial glycaemia, in part by reducing glucagon secretion.     

Intestinal immune activation in presumed post-infectious functional dyspepsia

Abstract  Functional dyspepsia (FD) symptoms may develop after an acute gastroenteritis. In post-infectious (PI) irritable bowel syndrome, persisting low-grade colonic inflammation and increased enterochromaffine cells (EC) counts have been reported. The aim was to compare signs of inflammation and EC hyperplasia on duodenal biopsies in presumed PI-FD and unspecified-onset (U-)FD. Duodenal biopsies were obtained in 12 U-FD and 12 PI-FD (on average 13 months after the acute event) patients. The presence of intra-epithelial, intravillar, and the number of CD3, CD4, CD8 and CD68+ cells per crypts, and the mean number of Chromogranine A (CA) positive cells per villus were compared. We also measured gastric emptying and assessed proximal stomach function with a barostat. Data are shown as mean ± SEM. Focal aggregates of T cells and focal CD8+ aggregates, were found in PI-FD but not in U-FD patients (respectively 5/12 vs 0/12, P  = 0.02 and 5/9 vs 0/11, P  < 0.01). In patients with focal aggregates, gastric emptying was delayed (189 ± 37 min vs 98 ± 11 min, P  = 0.002). The number of CD4+ cells per crypt (0.52 ± 1.6 vs 1.22 ± 2.18, P  = 0.04), and the number of intravillar CD4+ cells (0.5 ± 0.2 vs 2.7 ± 0.7, P  = 0.01) were reduced, while the number of CD68+ cells per crypt was increased (0.64 ± 0.13 vs 0.40 ± 0.05, P  = 0.03) in PI-FD. The number of EC and CA were comparable. PI-FD is associated with persisting focal T-cell aggregates, decreased CD4+ cells and increased macrophage counts surrounding the crypts. This may indicate impaired ability of the immune system to terminate the inflammatory response after acute insult.