The role of fat and cholecystokinin in functional dyspepsia

The main factors involved in the pathophysiology of fat induced dyspepsia were investigated by reviewing a series of controlled double blind randomised studies which sought to determine the role of nutrient fat and the postprandial release of cholecystokinin (CCK) in the development of dyspeptic symptoms in healthy volunteers and in patients with functional dyspepsia. The studies showed that during distension of the stomach, lipids are a major trigger of dyspeptic symptoms such as nausea, bloating, pain, and fullness, and that they modulate upper gastrointestinal sensations and symptoms in a dose related fashion. CCK is a major mediator of the sensitisation of gastric perception by lipids in patients with functional dyspepsia as the CCK-A receptor antagonist dexloxiglumide markedly diminishes this effect. The studies provide important insights into the mechanisms underlying gastrointestinal perception in response to fat and the role of CCK in patients with functional dyspepsia.     

Effect of CCK-1 antagonist, dexloxiglumide, in female patients with irritable bowel syndrome: a pharmacodynamic and pharmacogenomic study

BACKGROUND: Cholecystokinin (CCK) is involved in gastrointestinal motor response to meals. The potential role of CCK receptor antagonists in functional gastrointestinal disorders is unclear. AIMS: To evaluate the effects of dexloxiglumide, a CCK-1 receptor antagonist, on gastrointestinal transit (GIT) and symptoms in patients with constipation-predominant IBS (C-IBS); and to explore the influence of CCK-1 receptor polymorphisms on gut transit and the pharmacodynamic response to therapy. METHODS: A total of 36 patients with C-IBS and normal to slow baseline colonic transit (CT) were randomized (double-blind, parallel design) to 7 days of dexloxiglumide 200 mg or placebo t.i.d. Daily bowel habits diaries and weekly relief of IBS symptoms were recorded. At the end of treatment, GIT and CT were measured. Peripheral blood DNA was examined for polymorphisms in genes controlling CCK: four related to CCK-1, one to the CCK gene promoter, and one related to CCK-2. The distributions of allelic variants and association with gastric emptying in response to dexloxiglumide and placebo were assessed. RESULTS: Dexloxiglumide was associated with accelerated gastric emptying t(1/2) (p= 0.004), and slower ascending colon emptying t(1/2) (p < 0.01), with no significant effect on overall CT or satisfactory relief of IBS. There was an association between CCK 779T > C polymorphism and slower rate of gastric emptying (p= 0.04). CONCLUSIONS: Dexloxiglumide accelerates gastric emptying and delays proximal but not overall CT in patients with C-IBS. Dexloxiglumide does not accelerate transit in C-IBS. The role of CCK-1 gene polymorphisms in delaying gastric emptying and in determining response to therapy deserves further study.     

Nutrient-specific modulation of gastric mechanosensitivity in patients with functional dyspepsia

Intraduodenal lipid infusion induces symptoms and increases sensitivity to gastric distension in patients with functional dyspepsia. To test whether these effects are specific for lipid, we compared the effects of intraduodenal infusions of either lipid or glucose on symptoms and gastric sensory and motor responses to gastric distension. Eighteen dyspeptic patients and nine controls were studied. The stomach was distended with a flaccid bag during isocaloric infusions (1 kcal/ml) of saline and either 10% Intralipid (nine patients) or 26.7% glucose (nine patients) into the duodenum. Dyspeptic symptoms and sensory thresholds for epigastric fullness and discomfort were assessed. Gastric pressure profiles during distensions were similar during lipid and glucose infusions in patients and controls, but both were significantly lower than during saline infusion. Lower volumes were required to induce fullness and discomfort in the patients compared with the controls. In the controls, the threshold volumes required to induce fullness and discomfort were greater during infusion of lipid and glucose than during saline infusion, but in the patients, the threshold volumes were increased during glucose infusion but further reduced during lipid infusion. Moreover, in the patients, nausea was more common during lipid than glucose infusion and did not occur during saline. The controls did not experience any symptoms during any infusion. In conclusion, intraduodenal lipid but not glucose sensitizes the stomach to distension in patients with functional dyspepsia but not in controls.     

Cholecystokinin in transient lower oesophageal sphincter relaxation due to gastric distension in humans.

BACKGROUND AND AIMS: Transient lower oesophageal sphincter relaxations (TLOSRs) has been found to be the main mechanism of gastro-oesophageal reflux. In dogs, cholecystokinin (CCK) is involved in their occurrence. The aim was to evaluate the role of endogenous and exogenous CCK in the occurrence of TLOSRs induced by gastric distension at constant pressure in humans. METHODS: Ten healthy volunteers were studied. Lower oesophageal sphincter pressure was monitored with a sleeve device and gastric distension was performed via an intragastric bag monitored by a barostat. During distensions, saline, CCK (30 ng/kg/h) or the CCK-A receptor antagonist loxiglumide (10 mg/kg/h) was perfused in a random double blind order. RESULTS: There was no significant difference between the number of TLOSRs during the different distensions with saline; CCK increased the number of TLOSRs at a mean rate of 13.1 compared with 9.1 with saline (p < 0.001). Loxiglumide significantly decreased the number of relaxations to 5.3 versus 8.3 under paired saline infusion (p < 0.001). CONCLUSIONS: In humans, CCK-A receptor subtype is involved in the occurrence of transient lower oesophageal sphincter relaxations induced by gastric distension.     

A pilot study on duodenal acid exposure and its relationship to symptoms in functional dyspepsia with prominent nausea

BACKGROUND: Duodenal hypersensitivity to acid and decreased duodenal clearance of exogenous acid have been reported in functional dyspepsia (FD). However, the relevance of these abnormalities to spontaneous duodenal acid exposure and dyspeptic symptoms in FD is unknown. AIMS: To determine spontaneous duodenal acid exposure and its relationship with symptoms, duodenal sensitivity to acid, and the effects of a 5-HT(3) receptor antagonist on duodenal responses to acid in FD. METHODS: Eleven FD patients with prominent nausea and 11 healthy controls underwent 24-h ambulatory duodenal pH monitoring with assessment of dyspeptic symptoms. On the next day, duodenal bolus infusions of 5 ml of acid and normal saline were given in a randomized double-blind manner and repeated after ondansetron or a placebo. RESULTS: Nighttime duodenal acid exposure was similar, but FD patients had lower duodenal pH and higher duodenal % time (pH < 4) than controls during the daytime and in the second postprandial 2 h (p < 0.05). Seven patients (64%) with duodenal acid exposure above the normal range had higher severity scores for several dyspeptic symptoms including nausea. However, the symptom severity was poorly or weakly correlated to duodenal pH, and brief duodenal acid infusion did not affect any symptoms. Duodenal responses to exogenous acid were unaffected by 5-HT(3) receptor antagonism. CONCLUSIONS: Spontaneous duodenal acid exposure is increased in a subset of FD patients with prominent nausea, and this is associated with more severe dyspeptic symptoms. However, a direct relationship between duodenal acid exposure and symptom severity is lacking.     

Dyspeptic symptoms associated with hypersensitivity to gastric distension induced by duodenal acidification

BACKGROUND AND AIM: Duodenal acidification might increase sensitivity to gastric distension, which seems to play a role in the genesis of dyspeptic symptoms in a subset of patients with functional dyspepsia. The aim of the present study was to investigate the characteristics of dyspeptic symptoms associated with hypersensitivity to gastric distension induced by duodenal acidification. METHODS: An infusion tube and a barostat bag were positioned in the duodenum and gastric fundus, respectively. Sensitivity to stepwise fundic distensions with severity scoring of the seven dyspeptic symptoms was assessed before and during duodenal acid infusion in 20 healthy subjects. RESULTS: Acid infusion significantly decreased the pressures and the corresponding wall tensions at the thresholds for discomfort. At the distending level of minimal distending pressure (MDP) + 2 mmHg, significantly higher scores of fullness and bloating were obtained during acid infusion. With distending stimuli of MDP + 4 and 6 mmHg, fullness, bloating, nausea, satiety, epigastric burning and epigastric pain were significantly more severe during acid infusion than before acid infusion. At the level of MDP + 8 mmHg, the severity of epigastric pain was significantly greater, compared with that before acid infusion. CONCLUSIONS: Duodenal acidification might aggravate dyspeptic symptoms through the induction of hypersensitivity to gastric distension in healthy individuals. Those symptoms are diverse and variable, depending on the strength of the distending stimuli.     

Luminal Stimuli Acutely Sensitize Visceromotor Responses to Distension of the Rat Stomach

Inflammation can enhance responses to different stimuli consistent with the development of hypersensitivity. To determine whether sequentially applied stimuli interact, we determined visceromotor responses (VMR) to gastric distension, measured at baseline and 60 min after instillation of saline, glycocholic acid (GCA) or ethanol through a gastrostomy in controls and rats with gastric ulcers. In another series of experiments, chemicals were administered before and 60 min after repeated distension of the stomach. Ethanol, but not saline or GCA, increased VMR in controls with a more significant rise in rats with gastric ulcerations. GCA increased responses to gastric distension in controls, whereas GCA and ethanol enhanced responses to gastric distensions in rats with gastric ulcers. Responses to saline, GCA, or ethanol were not affected by repeated noxious distension of the stomach. Luminal stimuli can trigger visceromotor responses and sensitize gastric afferents to mechanical stimulation, thus potentially contributing to dyspeptic symptoms. Supported by a grant from the National Institutes of Health (NS 35790).     

Rapid initial gastric emptying and hypersensitivity to gastric filling in functional dyspepsia: effects of duodenal lipids

OBJECTIVE: Impaired distension-induced gastric accommodation and hypersensitivity to distension have been demonstrated by gastric barostat in patients with functional dyspepsia (FD). In this study we investigated distension-induced responses to gastric filling with water in healthy volunteers and FD patients, using non-invasive ultrasonography. MATERIAL AND METHODS: Eighteen healthy volunteers and 18 FD patients were given infusions of 10 ml saline or lipid (3 kcal/ml) through a nasoduodenal tube. After tube retraction, the stomach was filled with 1000 ml water during 10 min. Intragastric volume was monitored by 3D ultrasonography, and fullness, pain and nausea were assessed. RESULTS: Compared with healthy volunteers, patients with FD had faster gastric emptying at 5 min (p = 0.0008) and reported more fullness (p = 0.006) during gastric filling with water. Prior duodenal lipid exposure reduced initial gastric emptying rate in FD patients to the level seen in healthy volunteers. However, despite similar gastric volumes, the patients still reported greater fullness (p = 0.002) and nausea (p = 0.01). CONCLUSIONS: Patients with FD had abnormally rapid initial gastric emptying of water and hypersensitivity to gastric filling. Though normalizing gastric emptying rate and volumes, duodenal lipid exposure did not improve hypersensitivity. Rapid initial gastric emptying of water might be a sign of impaired distension-induced gastric accommodation.     

Effect of the 5-HT3 receptor antagonist, ondansetron, on gastric size in dyspeptic patients with impaired gastric accommodation

BACKGROUND: A reduction of gastric accommodation after a meal has been documented in patients with idiopathic dyspepsia. In these patients the administration of a 5-HT3 receptor antagonist may reduce some of the dyspeptic symptoms; it is not clear however, whether these drugs influence gastric adaptation to distension as well. AIM: To evaluate the effects of the 5-HT3 receptor antagonist, ondansetron, on gastric distension after a liquid meal in dyspeptic patients with reduced gastric accommodation. METHODS: Before and after a 500 ml water load, gastric accommodation (area of the proximal and distal stomach) was evaluated using real-time ultrasonography in 21 idiopathic dyspepsia patients and 26 healthy controls. In dyspeptic patients, the test was repeated twice: after the administration of placebo and after ondansetron 8 mg i.v. (in both cases, 15 min prior to the water load). Secondary outcomes were epigastric pain, fullness and nausea as assessed by a visual analogue scale at basal and after ondansetron. RESULTS: Fasting gastric size was similar in dyspeptic and controls. Compared with controls, dyspeptic patients showed a statistically significant smaller area of the proximal stomach (14.7+/-1.2 cm(2) vs. 18.6+/-1.4 cm(2), respectively; p=0.0247). In dyspeptic patients, gastric proximal and distal size did not change significantly following placebo, whereas after the administration of ondansetron the mean area of the proximal and distal stomach significantly increased (proximal stomach: 14.6+/-1.6 cm(2) placebo, 20.4+/-1.9 cm(2) ondansetron, p=0.0095; distal stomach: 8.9+/-0.9 placebo, 11.4+/-1.2cm(2) ondansetron, p=0.0409). Of the symptoms, only nausea was significantly reduced after ondansetron. CONCLUSION: In dyspeptic patients with impaired gastric accommodation, ondansetron reverts gastric accommodation to within the range of controls.     

Cholecystokinin hyperresponsiveness in functional dyspepsia

Functional dyspepsia (FD) is a common disorder of yet uncertain etiology. Dyspeptic symptoms are usually meal related and suggest an association to gastrointestinal (GI) sensorimotor dysfunction. Cholecystokinin (CCK) is an established brain-gut peptide that plays an important regulatory role in gastrointestinal function. It inhibits gastric motility and emptying via a capsaicin sensitive vagal pathway. The effects on emptying are via its action on the proximal stomach and pylorus. CCK is also involved in the regulation of food intake. It is released in the gut in response to a meal and acts via vagal afferents to induce satiety. Furthermore CCK has also been shown to be involved in the pathogenesis of panic disorder, anxiety and pain. Other neurotransmitters such as serotonin and noradrenaline may be implicated with CCK in the coordination of GI activity. In addition, intravenous administration of CCK has been observed to reproduce the symptoms in FD and this effect can be blocked both by atropine and loxiglumide (CCK-A antagonist). It is possible that an altered response to CCK may be responsible for the commonly observed gastric sensorimotor dysfunction, which may then be associated with the genesis of dyspeptic symptoms.     

Rapid gastric emptying, rather than delayed gastric emptying, might provoke functional dyspepsia

It has been suggested that there could be three possible mechanisms of gastric dysfunction in patients with FD: (i) delayed gastric emptying, (ii) impaired gastric accommodation of food intake, and (iii) hypersensitivity to gastric distention. Postprandial fullness seems to be the most severe symptom in patients who report aggravation of their symptoms after meals. Therefore, it has been assumed that delayed gastric emptying and consequent prolonged antral distension could reduce hunger, increase satiety, and even cause gastric discomfort, all of which would pose a significant barrier to adequate nutrition. We previously reported that postprandial water intake inhibits gastric antral motility along with an increase of cholecystokinin (CCK) in normal subjects. We assumed that the rapid increase of CCK after water intake was initiated by a feedback mechanism related to the inflow of fatty chyme into the duodenum that inhibits gastric antral activity. This duodeno-gastric interaction is known as the "duodenal break." We also reported that total gastric emptying was more rapid after the intake of a high-viscosity liquid meal than after a low-viscosity meal, because the low-viscosity liquid meal inhibits gastric emptying after rapid initial inflow into the duodenum. Considering these results, we hypothesized that rapid gastric emptying, rather than delayed gastric emptying, could be a cause of FD. In some patients with postprandial distress syndrome (PDS), we have found a significant correspondence between PDS-related dyspepsia and accelerated gastric emptying in the early postprandial period. It is worth emphasizing that the duodenum and the duodeno-gastric interaction (duodenal break) could have an important role in the pathophysiology of FD. We consider that rapid gastric emptying might be a more important factor than delayed gastric emptying in patients with FD.     

Abnormal clearance of exogenous acid and increased acid sensitivity of the proximal duodenum in dyspeptic patients

BACKGROUND & AIMS: Although acid is likely to play a role in the genesis of symptoms in dyspeptic patients, most studies have failed to show an increase in gastric acid secretion. The aim of this study was to investigate clearance of acid from the duodenum and its relationship with symptoms in patients with functional dyspepsia. METHODS: Twelve patients and 10 healthy volunteers were studied using an assembly allowing recording of pressures and pH. Acid and saline were infused intraduodenally during phase II and postprandially. Sensations were scored before and 1 and 5 minutes after each infusion. RESULTS: After acid infusion in the fasting period, a greater increase in acidity in the duodenal bulb (P = 0.007) and fewer duodenal pressure waves (P = 0.002) were observed in dyspeptic patients. No significant differences in the time with pH < 4 and duodenal motor activity were observed in the postprandial period. Acid infusion reproducibly increased the sensation of nausea in patients (P < 0.001) but not in the controls. Saline infusion had no effect on upper gastrointestinal sensations. CONCLUSIONS: In fasting dyspeptic patients, clearance of exogenous acid from the duodenal bulb and duodenal motor activity are decreased. The duodenal bulb in dyspeptic patients is hypersensitive to acid infusion, which induces the nausea.     

Proximal gastric compliance and perception of distension in type 1 diabetes mellitus: effects of hyperglycemia

OBJECTIVES: Upper GI symptoms and disordered gastric motor function occur frequently in patients with type 1 diabetes mellitus and may be influenced by the blood glucose concentration. The aims of this study were to evaluate proximal gastric compliance and perception of gastric distension during euglycemia and hyperglycemia in unselected patients with type 1 diabetes. METHODS: Ten randomly selected patients with type 1 diabetes were studied. On a single day, isovolumetric and isobaric distensions of the proximal stomach were performed during both euglycemia (blood glucose, 6 mmol/L) and hyperglycemia (15 mmol/L), in randomized order. Sensations of fullness, nausea, and bloating were scored using visual analog scales during each step. Results were compared with those obtained in 10 healthy subjects studied during euglycemia. RESULTS: During euglycemia, perceptions of fullness (p < 0.01), nausea (p < 0.01), and bloating (p < 0.05) were greater during gastric distension in patients with diabetes when compared with healthy controls. In the patients, hyperglycemia increased gastric compliance (p < 0.05) when compared to euglycemia. CONCLUSIONS: In unselected patients with type 1 diabetes 1) the perception of gastric distension during euglycemia is increased compared with healthy controls, and 2) hyperglycemia increases proximal gastric compliance.     

Regulation of fat-stimulated neurotensin secretion in healthy subjects

CONTEXT: Cholecystokinin (CCK) and neurotensin are stimulated during meal intake by the presence of fat in the small intestine. The sequence of events suggests that fat hydrolysis is crucial for triggering the release. OBJECTIVE: The aim of this study was to investigate whether CCK mediated the effect of intraduodenal (ID) fat on neurotensin secretion via CCK-1 receptors. SETTING: This was a single center study; 34 male volunteers were studied in consecutive, randomized, double-blind, cross-over studies. SUBJECTS AND METHODS: CCK and neurotensin release were quantified in: 1) 12 subjects receiving an ID fat infusion with or without 60 mg orlistat, an irreversible inhibitor of gastrointestinal lipases, in comparison to vehicle; 2) 12 subjects receiving ID long chain fatty acids (C18s), ID medium chain fatty acids, or ID vehicle; and 3) 10 subjects receiving ID C18 with and without the CCK-1 receptor antagonist dexloxiglumide or ID vehicle plus iv saline (placebo). Hormone concentrations were measured by specific RIA systems. RESULTS: ID fat induced a significant increase in CCK and neurotensin concentrations (P < 0.001-0.002). Inhibition of fat hydrolysis by orlistat abolished both effects. C18 stimulated CCK and neurotensin release (P < 0.001, respectively), whereas medium chain fatty acid was ineffective. Dexloxiglumide administration partially blocked the effect of C18 on neurotensin; the effect was only present in the first phase of neurotensin secretion. CONCLUSIONS: Generation of C18 through hydrolysis of fat is a critical step for fat-induced stimulation of neurotensin in humans; the signal is in part mediated via CCK release and CCK-1 receptors.     

莫沙必利改善夜间消化不良症状的随机、双盲、安慰剂平行对照研究

功能性消化不良（FD）的发病机制尚未完全明了。夜间上腹部症状是影响FD患者生活质量的重要因素。促动力药对夜间FD症状的治疗作用和机制不详。目的：探讨莫沙必利对FD患者夜间消化不良症状的治疗作用。方法：采用随机、双盲、安慰剂平行对照的前瞻性设计，连续选取主诉有夜间FD症状（上腹部疼痛、饱胀、嗳气）的患者，经一周安慰剂治疗筛选，无安慰剂治疗反应者分别给予莫沙必利（5mgtid）和安慰剂治疗。治疗前后分别行夜间症状评估以及夜间胃内DH值和胆红素联合检测。结果：共纳入43例有夜间FD症状的患者，28例对安慰剂治疗无反应。治疗后，莫沙必利组夜间上腹部疼痛、饱胀、暖气的症状积分均明显降低（R0．05），夜间胃内pH值和胆红素吸收值〉0．14的时间百分比均明显降低（P〈O．05）；而安慰剂组上述指标无明显差异（P〉O．05）。莫沙必利组夜间症状积分改善程度与夜间胃内pH值和胆红素吸收值〉O．14的时间百分比降低程度有明显相关性（P〈O．05）。结论：莫沙必利能显著改善夜间FD症状．其机制可能与减轻夜间胃十二指肠胆汁反流有关。     

Role of cognitive factors in symptom induction following high and low fat meals in patients with functional dyspepsia

BACKGROUND: and aims: Dietary fat plays a role in the pathophysiology of symptoms in functional dyspepsia (FD). In healthy subjects, cognitive factors enhance postprandial fullness; in FD patients, attention increases gut perception. We hypothesised that the information given to patients about the fat content of a meal would affect dyspeptic symptoms. METHODS: Fifteen FD patients were each studied on four occasions in a randomised double blind fashion. Over two days they ingested a high fat yoghurt (HF) and over the other two days a low fat yoghurt (LF). For each yoghurt, the patients received the correct information about its fat content on one day (HF-C, LF-C) and the opposite (wrong) information on the other day (HF-W, LF-W). Dyspeptic symptoms, plasma cholecystokinin (CCK) concentrations, and gastric volumes were evaluated. RESULTS: Both the fat content and information about the fat content affected fullness and bloating scores-both were higher after HF-C compared with LF-C, and LF-W compared with LF-C, with no differences between HF-C and HF-W. Nausea scores were higher after HF compared with LF, with no effect of the information about fat content. No differences between discomfort and pain scores were found between study conditions. Plasma CCK and gastric volumes were greater following HF compared with LF, with no effect of the information given to the patients. All differences are p<0.05. CONCLUSIONS: Cognitive factors contribute to symptom induction in FD. Low fat foods may also elicit symptoms if patients perceive foods as high in fat, while CCK and gastric volumes do not appear to be affected by cognitive factors.     

Does Helicobacter pylori infection increase gastric sensitivity in functional dyspepsia?

The role of Helicobacter pylori infection in the pathogenesis of functional dyspepsia is debated. It is known that a substantial fraction of dyspeptic patients manifest a low discomfort threshold to gastric distension. This study investigated the symptomatic pattern in 27 H pylori positive and 23 H pylori negative patients with chronic functional dyspepsia, and potential relations between infection and gastric hyperalgesia. Specific symptoms (pain, nausea, vomiting, bloating/fullness, early satiety) were scored from 0 to 3 for severity and frequency (global symptom scores: 0-15). The mechanical and perceptive responses to gastric accommodation were evaluated with an electronic barostat that produced graded isobaric distensions from 0 to 20 mm Hg in 2 mm Hg steps up to 600 ml. Gastric compliance (volume/pressure relation) and perception (rating scale: 0-10) were quantified. Standard gastrointestinal manometry and recorded phasic pressure activity at eight separate sites during fasting and postprandially were also assessed. H pylori positive and H pylori negative patients manifested similar severity and frequency of specific symptoms and global symptom scores (mean (SEM)) (severity: 9.5 (2.0) v 9.0 (2.1); frequency: 10.8 (2.0) v 9.7 (2.2)). No differences were seen either in gastric compliance (53 (4) ml/mm Hg v 43 (3) ml/mm Hg) or in gastric perception of distension (slope: 0.50 (0.05) v 0.53 (0.06)). Postprandial antral motility was significantly decreased in H pylori positive patients (two hours motility index: 10.4 (0.6) v 12.6 (0.5); p < 0.05). It is concluded that H pylori infected patients with functional dyspepsia present no distinctive symptoms by comparison with H pylori negative counterparts and H pylori infection is associated with diminished postprandial antral motility but it does not increase perception of gastric distension.     

Relations between upper abdominal symptoms and gastric distension abnormalities in dysmotility like functional dyspepsia and after vagotomy.

Postprandial bloating and fullness are commonly found both in dysmotility like functional dyspepsia, and after vagotomy but the relation between gastric accommodation and symptom production has not been investigated. Intragastric pressure levels and symptoms developed during controlled distension of the gastric fundus were recorded in nine patients with functional dyspepsia, in seven patients after truncal vagotomy, and in 11 healthy volunteers. The procedure was repeated after ingestion of a liquid nutrient meal (250 ml; 250 kcal). Gastric tone, expressed as the average value of pressure over the distension period was lower in controls (median: 11.3 mm Hg) than in either the dyspeptic patients (median: 16.48 mm Hg) or postvagotomy patients (median: 19.12 mm Hg) (p < 0.05). Meal ingestion reduced gastric tone in controls, but no significant change occurred in either the dyspepsia or the postvagotomy patients. Volumes at which discomfort was elicited by distension during fasting were lower both in dyspeptic patients (median: 210 ml) and in postvagotomy patients (median: 180 ml) than in healthy volunteers (median: 660 ml) (p < 0.05). Discomfort thresholds were unaffected by meal ingestion. These results suggest that a disturbance of gastric relaxation may be related to symptom development in dysmotility like functional dyspepsia, while similarities between dyspeptic patients and postvagotomy patients suggest that the impaired gastric accommodation in functional dyspepsia may be due to an underlying vagal defect.     

Gallbladder contractility and volume characteristics in gallstone dyspepsia

AIM:It is difficult to differentiate gallstone dyspepsia and functional dyspepsia by clinical symptoms and signs. We hypothesized that gallstone dyspepsia was related to abnormal gallbladder motility. We aimed to differentiate gallstone dyspepsia from functional dyspepsia by measuring gallbladder motility.METHODS: We measured gallbladder volume changes in response to gastric distension (saline 500mL) and fatty meal in 10normal volunteers (controls) and 62 patients with gallstones and dyspepsia before cholecystectomy. Forty cholecystectomized patients were symptom free or had improvement (group I), while the remaining 22 patients had persistent dyspepsia (group Ⅱ). Gallbladder volume change and ejection fraction were analyzed and compared among the three groups.RESULTS:In group I, there were significant decreases in gallbladder volumes 5-25 rain after gastric distension,compared to fasting volumes. Compared to normal volunteers and group Ⅱ, group I had significantly decreased gallbladder volumes 10-20min after drinking 500mL of normal saline and 10 to 50min after eating fatty meal.CONCLUSION:Our results support the hypothesis that increased gallbladder contraction after gastric distension or fatty meal may be related to dyspeptic symptoms in uncomplicated gallstone disease. These findings may be useful in differentiating functional dyspepsia from gallstone dyspepsia, patients with the latter disease may benefit from laparoscopic cholecystectomy.     

Influence of corticotropin-releasing hormone on gastric sensitivity and motor function in healthy volunteers

BACKGROUND: As stress may be involved in the generation of functional dyspeptic symptoms, we evaluated the effect of the stress hormone, corticotropin-releasing hormone, on proximal stomach function. Twelve healthy volunteers [six women; 23 years (20-26 years)] underwent a barostat study on 2 days. During the infusion of corticotropin-releasing hormone (2.3 microg/kg/h) or saline, a stepwise distension protocol was performed followed by ingestion of a liquid meal (Nutridrink, 200 ml, 300 kcal). RESULTS: Corticotropin-releasing hormone infusion induced a significant increase in cortisol levels and basal volumes compared with placebo. The threshold for discomfort, meal-induced accommodation, dyspeptic symptoms, heart rate and blood pressure were all not significantly altered by corticotropin-releasing hormone infusion. CONCLUSION: In healthy volunteers, peripheral infusion of corticotropin-releasing hormone reduces basal fundic tone, but has no effect on meal-induced accommodation or visceral sensitivity to gastric distension. Our findings suggest that in healthy volunteers, peripheral corticotropin-releasing hormone seems not to be involved in the onset of dyspeptic symptoms.