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.     

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.     

Evaluation of duodenal hypersensitivity induced by duodenal acidification using transnasal endoscopy

Background and Aim: Although duodenal hypersensitivity has been suggested as one of the causes of functional dyspepsia (FD), a practical method to clarify this has not yet been established. The aim of this study was to evaluate whether patients with FD have duodenal hypersensitivity to acid, using transnasal endoscopy. Methods: In all, 44 patients with FD and 16 healthy volunteers were enrolled, and all the subjects received transnasal endoscopy in the morning after overnight fasting. After ordinary transnasal endoscopy, an infusion tube was introduced into the duodenal bulb by transnasal endoscopy and acid (20 mL, 0.1 N HCl, 20 mL/min, 36.5°C) was injected via the infusion tube. The severity of 12 symptoms was assessed by each subject using a 100‐mm visual analogue scale. The maximum severity scale was defined as the maximum score of the symptom severity scale. The total score was defined as the aggregate score of the maximum severity scale of the 12 symptoms. The maximum severity scales and the total scores between patients with FD and healthy volunteers were evaluated. Results: The maximum severity scales of nine symptoms increased significantly more after acid infusion in patients with FD than in healthy volunteers (P < 0.05). There were significant differences in the total scores (patients with FD vs healthy volunteers 233.8 ± 37.8 vs 63.9 ± 14.6, mean ± standard error of the mean, P < 0.001). Conclusions: Duodenal acidification using transnasal endoscopy enabled the evaluation of duodenal hypersensitivity to acid in healthy volunteers and patients with FD.     

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。     

Real-time evaluation of dyspeptic symptoms and gastric motility induced by duodenal acidification using noninvasive transnasal endoscopy

Background  Although different pathophysiological mechanisms have been suggested to be involved in functional dyspepsia, a practical method to clarify them has not been established. The aim of this study was to evaluate dyspeptic symptoms and gastric motility induced by duodenal acidification using transnasal endoscopy. Methods  Fourteen healthy volunteers (mean age, 32 years) were enrolled. Transnasal endoscopy was performed on all fasting volunteers. Dyspeptic symptoms and antral contractions were evaluated before and after duodenal infusions of pure water (20 ml/min for 5 min) and acid (0.1 N HCl, 20 ml/min for 5 min). The severity of various symptoms was assessed by each subject using a 10-cm visual analog scale every 2 min. The maximum severity scale was calculated as the mean of the individual maximum values. The motility number was defined as the mean number of antral contractions in 1 min. Results  The maximum severity score for a heavy feeling in the stomach and other symptoms significantly increased after the acid infusion compared with after the pure water infusion. During pure water infusion, there were no changes in the motility number. On the other hand, the motility number significantly decreased after duodenal acidification (before vs. after, 2.93 ± 0.12 times vs. 1.11 ± 0.23 times, P < 0.0001). Conclusions  Duodenal acid exposure induces dyspeptic symptoms and inhibits antral motility. Transnasal endoscopy enabled us to evaluate both dyspeptic symptoms and gastric motility simultaneously.     

Diet, food intake, and disturbed physiology in the pathogenesis of symptoms in functional dyspepsia

Functional dyspepsia (FD) remains a relatively poorly characterized gastrointestinal disorder of unknown etiology that is frequently difficult to manage. A systematic review of the literature relating to food intake and FD is summarized here. Many patients with FD report symptoms after meal ingestion, including fullness, bloating, epigastric pain, nausea, and vomiting, and this has been interpreted as indicative of an underlying "motor disorder of the stomach or small intestine." Such hypotheses are, however, still largely unsubstantiated, and the data that do exist are inconclusive, particularly as few studies have directly examined the temporal relationships between dyspeptic symptoms, meal ingestion, and disordered gastric motility. Moreover, studies attempting to relate symptoms to specific disturbances in gastric motor function have, in most cases, not evaluated symptoms concurrently with the function test, and/or have used suboptimal symptom scoring to quantify symptoms. Furthermore, the term "early satiety" has been used loosely as a symptom, rather than a quantitative measure of food intake. Currently, the most widely accepted mechanism underlying FD is visceral hypersensitivity, which may contribute to both enhanced motor and symptomatic responses to food ingestion. However, the possible contribution of food and dietary habits to the induction and/or exacerbation of dyspeptic symptoms represents a relatively new area-despite frequent reports by patients that their symptoms are often related to food ingestion; this association has not been formally assessed. Dietary assessments have frequently implicated fatty foods in symptom induction, and these findings are supported by laboratory-based studies, particularly the demonstration that FD patients more often experience symptoms after intraduodenal infusions of fat, than glucose. Further studies into the potential role of dietary factors in the induction of dyspeptic symptom are required to establish whether dietary therapies have any place in the management of FD.     

Abnormalities of serotonin metabolism and their relation to symptoms in untreated celiac disease.

BACKGROUND AND AIMS: Serotonin (5-hydroxytryptamine [5-HT]) is a key modulator of gut function that in excess causes nausea, vomiting, and diarrhea. We recently showed that patients with post-infective irritable bowel syndrome have increased postprandial release of 5-HT associated with low-grade T-cell mediated inflammation. Celiac disease is another common disease in which a T-cell enteropathy is associated with increased mucosal 5-HT levels. Our aim was to determine how this inflammatory lesion influenced 5-HT bioavailability and how changes in 5-HT related to the symptoms of nausea, vomiting, and diarrhea seen in untreated celiac patients. METHODS: Fasting plasma and platelet 5-HT and postprandial plasma 5-HT levels were measured after a high-carbohydrate meal in celiac patients (n = 18) and healthy controls (n = 18) using high-pressure liquid chromatography. Dyspepsia was assessed during the postprandial period using a questionnaire. Finally, we compared the histology and mucosal 5-HT levels in duodenal biopsy specimens from celiac patients and controls. RESULTS: Celiac patients had increased 5-HT-containing enterochromaffin cell numbers and significantly higher peak plasma 5-HT levels (P = .0002), postprandial area under the curve (P = .0006), and platelet 5-HT stores (P = .031) than controls. Peak 5-HT levels correlated significantly with postprandial dyspepsia scores (P = .005). Celiac patients had higher duodenal 5-HT levels (P = .007) than controls. CONCLUSIONS: Celiac disease is associated with increased mucosal 5-HT content and enhanced 5-HT release from the upper small bowel, which correlates with postprandial dyspepsia. Serotonin excess may mediate dyspeptic symptoms in untreated celiac disease.     

Symptoms and pathophysiological correlations in patients with constipation and functional dyspepsia

INTRODUCTION: Patients with constipation often report dyspeptic symptoms, but whether constipation is associated with specific dyspeptic symptoms and altered gastrointestinal (GI) motility, remains to be established. Our aim was to study symptoms association and GI motility parameters in patients with constipation and functional dyspepsia. PATIENTS AND METHOD: 42 patients with different symptoms and severity of constipation and dyspepsia were enrolled. Scintigraphic gastric emptying, colonic transit time and gallbladder contraction were studied in all subjects. RESULTS: No significant association was observed between individual symptoms of constipation and dyspepsia. Patients with more severe constipation did not have higher dyspepsia severity scores. Colonic transit time, gastric half emptying and gallbladder contraction were not significantly correlated. Although patients with severe nausea had faster colonic transit than those with absent/mild symptom (19 +/- 2 vs. 48 +/- 7 h; p < 0.05), the multivariate analysis only revealed a significant association between severe postprandial fullness, delayed t1/2 (OR 1.05, CI 1-1.1) and impaired gallbladder contraction (OR 0.94, CI 0.89-0.99). CONCLUSIONS: Constipation was not associated with severity, or any particular dyspeptic symptom. Although motor abnormalities of both colon and proximal GI tract regions existed in the subset of constipated dyspeptic patients, they did not seem associated with the genesis of different dyspeptic symptoms.     

Duodenal epithelial transport in functional dyspepsia: Role of serotonin

AIM: To investigate functional duodenal abnormalities in functional dyspepsia (FD) and the role of serotonin (5-hydroxytryptamine, 5-HT) in mucosal ion transport and signalling. METHODS: Duodenal mucosal biopsies were obtained from 15 patients with FD and 18 healthy controls. Immunohistochemistry was used to study the number of 5-HT-containing cells and real-time polymerase chain reaction for expression of 5-HT receptors 1A, 1B, 2A, 2B, 3A, 3B, 3C, 3D, 3E, 4 and 7, as well as expression of the serotonin re-uptake transporter (SERT) gene SLC6A4 and tryptophan hydroxylase 1 (TPH1). Biopsies were mounted in Ussing chambers for evaluation of basal and 5-HT-stimulated short-circuit current (SCC). RESULTS: Conductance was lower in FD [42.4 ± 4.7 mS/cm² (n = 15) vs 62.5 ± 4.5 mS/cm² (n = 18), P = 0.005]. 5-HT induced a dose dependent rise in SCC in both FD (n = 8) and controls (n = 9), the rise was lower in FD (P < 0.001). Mean number of 5-HT stained cells per high power field was the same [34.4 ± 8.4 in FD (n = 15) and 30.4 ± 3.7 in controls (n = 18), P = 0.647]. The following genes were highly expressed: 5-HT receptor HTR3E, HTR4, HTR7, SERT gene (SLC6A4) and TPH1. Differences in expression levels were observed for HTR3E (higher expression in FD, P = 0.008), HTR7 (lower expression in FD, P = 0.027), SLC6A4 (higher expression in FD, P = 0.033) and TPH1 (lower expression in FD, P = 0.031). CONCLUSION: Duodenal ion transport in response to exogenous 5-HT is abnormal in FD patients and associated with high expression of the HTR3E receptor and the serotonin transporter.     

Impact of coexisting irritable bowel syndrome on symptoms and pathophysiological mechanisms in functional dyspepsia

Epidemiological studies suggest considerable overlap between functional dyspepsia (FD) and irritable bowel syndrome (IBS). AIM: The aim of the present study was to investigate whether coexisting IBS is also associated with symptom pattern or pathophysiology in FD. METHODS: In 309 consecutive FD patients (207 women, age 42 +/- 0.8 yr), questionnaires were used to assess the dyspepsia symptom pattern and the Rome II criteria for IBS. The overall symptom severity was calculated adding the severity score (0-3, 0 = absent, 3 = severe) of eight dyspepsia symptoms. All patients underwent Helicobacter pylori testing, gastric barostat to determine sensitivity to distention and accommodation to a meal, and gastric emptying breath test. RESULTS: Fifty-four percent of the patients had FD alone, whereas 46% had FD + IBS. FD + IBS patients were more likely to be female (75%vs 60%, p < 0.01) and to have a greater weight loss (5.4 +/- 0.6 vs 3.5 +/- 0.4 kg, p < 0.05). Coexisting IBS did not increase the risk of having any of the dyspeptic symptoms but the overall symptom severity was significantly higher in FD + IBS (12.4 +/- 0.4 vs 9.8 +/- 0.3, p < 0.01). FD + IBS patients had a lower threshold for first perception (2.9 +/- 0.3 vs 3.8 +/- 0.3 mmHg, p < 0.05) and for discomfort (7.9 +/- 0.4 vs 9.5 +/- 0.5 mmHg, p < 0.05) and a greater prevalence of hypersensitivity to gastric distention (44%vs 28%, p < 0.05). Gastric emptying, accommodation to a meal, and prevalence of H. pylori infection did not differ in the two groups. CONCLUSION: About half of the FD patients fulfill the Rome II criteria for IBS. FD + IBS is more prevalent in female patients and is associated with a higher weight loss, with greater overall symptom severity, and with hypersensitivity to distention.     

Correlation between oesophageal acid exposure and dyspeptic symptoms in patients with nonerosive reflux disease

BACKGROUND & AIMS: Oesophageal acidification induces dyspeptic symptoms in healthy individuals. This study aimed to evaluate the correlation between oesophageal acid exposure and dyspeptic symptoms in patients with nonerosive reflux disease. METHODS: A total of 68 patients with dominant symptoms of heartburn, negative upper gastrointestinal endoscopy and concomitant dyspeptic symptoms participated in the study. The severity of dyspepsia and reflux-related symptoms was evaluated, and 24-h gastro-oesophageal pH-monitoring study was performed in all patients at baseline and after 4 weeks of therapy with esomeprazole 40 mg. RESULTS: Oesophageal basal acid exposure was pathological in 43 patients and normal in 25 patients, with a similar prevalence and severity of individual dyspeptic symptoms in the two groups. A significant correlation between reflux and dyspepsia scores was observed in the subgroup of patients with normal, but not in those with abnormal pHmetry (r=0.4, P=0.04 and r=0.2 P=0.07, respectively). After esomeprazole, a reduction in severity of dyspepsia (>or=50% with respect to baseline) was observed, independent of improvement of reflux-associated symptoms. Improvement in dyspepsia was, however, similar in patients with normal and abnormal basal acid exposure (14/25 vs. 33/43, respectively, P=NS). CONCLUSION: Dyspeptic symptoms coexist in a subset of nonerosive reflux disease patients, but prevalence and severity of the symptoms seems to be independent of oesophageal acid exposure.     

Pathophysiology of functional dyspepsia

Functional dyspepsia is a highly prevalent symptom complex and a heterogeneous disorder. Recent studies showed potential associations between specific pathophysiologic disturbances and dyspeptic symptoms. Delayed gastric emptying reported in about 30% of patients with functional dyspepsia is associated with the symptoms of postprandial fullness, nausea, and vomiting. Impaired gastric accommodation present in 40% of functional dyspepsia patients is found to be associated with early satiety. Hypersensitivity to gastric distension is observed in 37% of functional dyspepsia patients and associated with the symptoms of postprandial pain, belching, and weight loss. Psychosocial factors and altered response to duodenal lipids or acid have also been identified as pathophysiologic mechanisms.     

Helicobacter pylori colonization does not influence the symptomatic response to prokinetic agents in patients with functional dyspepsia

Functional dyspepsia (FD) is very common, but the pathogenesis of Helicobacter pylori leading to FD is still debated. The aim of this study was first to evaluate the impact of H. pylori colonization on the efficacy of Paspertase® (a metoclopramide plus exogenous enzymes regimen for FD patients) and, second, to compare the prevalence of H. pylori infection in FD patients with the general population. Seventy-four consecutive FD patients were enrolled undergoing Paspertase® treatment. The symptomatic response was evaluated according to 1–4 scales of six main dyspeptic symptoms (i.e. epigastric pain/discomfort, early satiety, heartburn, nausea/vomiting, abdominal fullness/bloating, and belching). Nine hundred and seventy healthy subjects undergoing a paid physical check-up were included to study the status of H. pylori colonization. The demographic data and basal symptom scores between 43 H. pylori -positive and 31 H. pylori -negative patients were not significantly different. Total and individual symptom scores improved significantly after 4 weeks of Paspertase® therapy ( P < 0.05), irrespective of H. pylori infection. The prevalences of H. pylori were very similar in FD patients and the general population (58.1 vs 58.0%, NS). In conclusion, these observations suggest that H. pylori colonization is not significant in FD patients of Taiwan while a short-term prokinetic medication is effective for these patients, irrespective of H. pylori status.     

Effect of the GABA(B) agonist baclofen in patients with symptoms and duodeno-gastro-oesophageal reflux refractory to proton pump inhibitors

BACKGROUND AND AIMS: A subset of patients with gastro-oesophageal reflux disease (GORD) with refractory symptoms during therapy with proton pump inhibitors (PPIs), have persistent non-acid duodeno-gastro-oesophageal reflux (duodenal reflux). The aim of the present study was to investigate the effect of the GABA(B) receptor agonist baclofen, which was shown to inhibit the occurrence of transient lower oesophageal sphincter relaxations (TLOSRs) in patients with persistent non-acid duodenal reflux during PPI therapy. METHODS: Patients were eligible for the study if they had persistent reflux symptoms, normal pH monitoring, and pathological Bilitec monitoring during PPI treatment. Upper gastrointestinal endoscopy and reflux symptom score were performed at the beginning of the study. Baclofen 5 mg three times daily was associated with treatment, and was increased by 5 mg every fourth day until a maintenance dose of 20 mg three times daily was reached. A reflux symptom questionnaire, ambulatory pH monitoring, and Bilitec monitoring were repeated four days later while PPI and baclofen were continued. All data are given as mean (SEM) or median (interquartile range) and were compared using the Student's t test or the Mann-Whitney U test. RESULTS: Sixteen patients (11 women, mean age 46 (3) years) with persistent heartburn or regurgitation for at least three months, in spite of PPI therapy, were included in the study. Erosive oesophagitis was present in seven patients (five with grade 1, two with grade 2). Under PPI therapy alone, all patients had normal acid exposure (0.3 (0.05; 2.2)% of the time) but pathological duodenal reflux exposure (13.8 (11.8; 15.5)% of the time). After addition of baclofen 20 mg three times daily, acid exposure was similar (0.4 (0.15; 2.3)% of the time; NS) but duodenal reflux had significantly decreased (6.1 (0.8; 10.3)% of the time; p<0.05). The number of duodenal reflux episodes and the number of longlasting duodenal reflux episodes (>5 minutes) was decreased, respectively, from 23 (14.5; 34) to 12 (5; 21) (p = 0.06) and from 5 (3; 8) to 2 (0.5;4.5) (p<0.05). The cumulative severity score for 14 reflux symptoms decreased from 10.3 (1.7) to 5.8 (1.3) (p<0.01). Four patients reported mild side effects of nausea or drowsiness. CONCLUSIONS: The GABA(B) receptor agonist baclofen improves duodenal reflux and associated reflux symptoms that persist during PPI therapy.     

Symptomatic benefit 1-3 years after H. pylori eradication in ulcer patients: impact of gastroesophageal reflux disease

OBJECTIVES: Eradication of Helicobacter pylori (H. pylori) infection markedly reduces the recurrence of duodenal and gastric ulcers. However, there is little information regarding its efficacy in resolving dyspeptic symptoms in ulcer patients. The primary aim of this study was to assess the effect of eradicating H. pylori infection on dyspeptic symptoms in ulcer patients. The secondary aim was to identify predictors of symptomatic response to H. pylori eradication. METHODS: A total of 97 dyspeptic patients with active duodenal and/or gastric ulceration associated with H. pylori infection and unrelated to NSAID use had the severity and character of their dyspeptic symptoms measured before and again 1-3 yr after H. pylori eradication therapy. RESULTS: Pretreatment, the median dyspepsia score was 12 (4-16). Posttreatment, 55% of those eradicated of H. pylori had resolution of dyspepsia (score <2) compared with 18% of those not eradicated of the infection (95% CI for difference, 11-62%). Of the ulcer patients 31% had symptoms and/or endoscopic evidence of coexisting gastroesophageal reflux disease (GERD) at initial presentation and this influenced the symptomatic response to eradication of H. pylori. Of the 22 patients with heartburn or acid reflux as the predominant presenting symptom, but no endoscopic esophagitis, only 27% experienced resolution of dyspepsia after H. pylori eradication, compared with 68% of the 59 without those as predominant symptoms (95% CI for difference, 18-63%). Only one of the five patients with coexisting endoscopic esophagitis at initial presentation experienced resolution of dyspepsia after H. pylori eradication. Symptomatic benefit was unrelated to time lapsed since the infection was eradicated. Only three of 50 subjects developed de novo GERD symptoms after eradication of H. pylori, whereas 21 of 36 subjects experienced resolution of GERD symptoms after eradication of the infection. CONCLUSIONS: A substantial proportion of ulcer patients have symptoms and/or signs of coexisting GERD at initial presentation and this reduces the symptomatic benefit from H. pylori eradication. However, we have found no evidence that eradicating H. pylori induces de novo GERD symptoms in ulcer patients.     

Effect of domperidone therapy on nocturnal dyspeptic symptoms of functional dyspepsia patients

AIM:To investigate the incidence of nocturnal dyspeptic symptoms in patients with functional dyspepsia(FD) and whether prokinetic drugs can alleviate them. METHODS:Eighty-five consecutive Chinese patients with FD were included in this study.One week after single-blinded placebo run-in treatment,baseline nocturnal intragastric pH,bile reflux and nocturnal dyspeptic symptoms of eligible patients,including epigastric pain or discomfort,abdominal distention and belching, were investigated with questionnaires.Pa...     

Effect of Profound Acid Suppression in Functional Dyspepsia: a Double-Blind,Randomized, Placebo-Controlled Trial

Background: Functional dyspepsia (FD) is defined as persistent or recurrent pain/discomfort centred in the upper abdomen, where no structural explanation for the symptoms is found. The role of drug treatment remains controversial. The aim in this study was to evaluate the effect of omeprazole 20 mg twice daily (b.i.d) and to test methods for symptom assessment. Methods: 197 patients fulfilling the criteria for FD were randomly allocated to double-blind treatment with omeprazole 20 mg b.i.d ( n = 100) or placebo ( n = 97) for 14 days. Patients with a known gastrointestinal disorder or with main symptoms indicating gastro-oesophageal reflux disease or irritable bowel syndrome were excluded. Helicobacter pylori testing and 24-h intra-oesophageal 24-h pH-metry were performed before randomization. The patients recorded dyspeptic symptoms on diary cards. Results: A stringent endpoint, 'complete symptom relief on the last day of treatment', was the primary efficacy variable. For the APT cohort, this was achieved in 29.0% and 17.7% on omeprazole and placebo, respectively (95% CI of difference (11.3%): -0.4%-23.0%, P = 0.057). Similar figures in the PP cohort were 31.0% and 15.5%, respectively (95% CI of difference (15.5%): 3.2%-27.7%, P = 0.018). The benefit of omeprazole in the PP cohort was confirmed by secondary endpoints such as, no dyspeptic symptoms on the last 2 days of treatment and overall treatment response. H. pylori status and the level of oesophageal acid exposure did not significantly influence the response to therapy. Conclusion: A subset of patients with FD will respond to therapy with omeprazole.     

Effect of profound acid suppression in functional dyspepsia: a double-blind,randomized, placebo-controlled trial

BACKGROUND: Functional dyspepsia (FD) is defined as persistent or recurrent pain/discomfort centred in the upper abdomen, where no structural explanation for the symptoms is found. The role of drug treatment remains controversial. The aim in this study was to evaluate the effect of omeprazole 20 mg twice daily (b.i.d) and to test methods for symptom assessment. METHODS: 197 patients fulfilling the criteria for FD were randomly allocated to double-blind treatment with omeprazole 20 mg b.i.d (n = 100) or placebo (n = 97) for 14 days. Patients with a known gastrointestinal disorder or with main symptoms indicating gastro-oesophageal reflux disease or irritable bowel syndrome were excluded. Helicobacter pylori testing and 24-h intra-oesophageal 24-h pH-metry were performed before randomization. The patients recorded dyspeptic symptoms on diary cards. RESULTS: A stringent endpoint, 'complete symptom relief on the last day of treatment', was the primary efficacy variable. For the APT cohort, this was achieved in 29.0% and 17.7% on omeprazole and placebo, respectively (95% CI of difference (11.3%): -0.4%-23.0%, P = 0.057). Similar figures in the PP cohort were 31.0% and 15.5%, respectively (95% Cl of difference (15.5%): 3.2%-27.7%, P = 0.018). The benefit of omeprazole in the PP cohort was confirmed by secondary endpoints such as, no dyspeptic symptoms on the last 2 days of treatment and overall treatment response. H. pylori status and the level of oesophageal acid exposure did not significantly influence the response to therapy. CONCLUSION: A subset of patients with FD will respond to therapy with omeprazole.     

Lack of association between esophageal acid sensitivity detected by prolonged pH monitoring and Bernstein testing

OBJECTIVES: Heartburn, a common medical symptom, is thought to be the result of acid reflux into the esophagus. Perfusion of the esophagus with exogenous acid (Bernstein test) in susceptible individuals causes heartburn. Temporal correlation between heartburn and pH drop in the esophagus from endogenous acid, as reflected by a positive symptom index (SI), provides further evidence of a correlation between acid in the esophagus and heartburn. We tested the relationship between heartburn and acid in the esophagus by determining the SI and Bernstein test results in the same individual. METHODS: Ninety-three patients with heartburn underwent 24-h pH monitoring and Bernstein testing. A Bernstein score that included the severity of heartburn and the time of heartburn onset during Bernstein test was calculated. The relationship between SI, Bernstein test, and Bernstein score was determined. RESULTS: Fifty-eight patients reported symptoms during the prolonged pH recording. A positive SI was detected in 27 patients. Forty-nine patients had a positive Bernstein test. There was no correlation between the patients with a positive SI and positive Bernstein test results. There was no correlation between SI and Bernstein score. A positive Bernstein test within 5 min of acid infusion did not predict heartburn during spontaneous reflux episodes of >/=5 min. CONCLUSIONS: The lack of association between symptoms induced by acid perfusion of the esophagus compared with symptoms following spontaneous reflux in the same individual suggests that the heartburn following acid perfusion and spontaneous heartburn are induced by different stimuli.     

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.