Background and Objective: To assess whether the combination of high waist-to-hip ratio (WHR) and elderly age is associated with higher risk of GERD. Material and Methods: A total of 16,996 subjects aged ≥20 years who received esophagogastroduodenoscopy (EGD) between January 2010 and December 2019. We evaluated the risk of GERD in different age groups and WHR groups in unadjusted analysis and multivariate logistic regression models for predictors of GERD. Results: There was a trend towards more participants with both age ≥65 years and WHR ≥ 1 (n = 129) (n = 66, 51%) than participants with age < 65 and WHR < 0.9 (n = 10,422) (n = 2814, 27%) presenting with GERD. Participants who had both age ≥ 65 years and high WHR ≥ 1 had the highest risk of any type of GERD (adjusted OR, 2.07; 95% CI, 1.44−2.96, p value < 0.05) based on multivariate logistic regression analysis. Conclusions: The combination of having a high WHR and being elderly was associated with a higher risk of GERD, and preventing central obesity in the elderly population reduced the risk of GERD and the requirement for medical resources.

Uncontrolled results suggest that diaphragmatic breathing (DB) is effective in gastroesophageal reflux disease (GERD) but the mechanism of action and rigor of proof is lacking. This study aimed to determine the effects of DB on reflux, lower esophageal sphincter (LES), and gastric pressures in patients with upright GERD and controls.

Adult patients with pH proven upright GERD were studied. During a high-resolution impedance manometry, study patients received a standardized pH neutral refluxogenic meal followed by LES challenge maneuvers (Valsalva and abdominal hollowing) while randomized to DB or sham. After that, patients underwent 48 hours of pH-impedance monitoring, with 50% randomization to postprandial DB during the second day.

On examining 23 patients and 10 controls, postprandial gastric pressure was found to be significantly higher in patients compared with that in controls (12 vs 7 mm Hg, P = 0.018). Valsalva maneuver produced reflux in 65.2% of patients compared with 44.4% of controls (P = 0.035). LES increased during the inspiratory portion of DB (42.2 vs 23.1 mm Hg, P < 0.001) in patients and healthy persons. Postprandial DB reduced the number of postprandial reflux events in patients (0.36 vs 2.60, P < 0.001) and healthy subjects (0.00 vs 1.75, P < 0.001) compared with observation. During 48-hour ambulatory study, DB reduced the reflux episodes on day 2 compared with observation on day 1 in both the patient and control groups (P = 0.049). In patients, comparing DB with sham, total acid exposure on day 2 was not different (10.2 ± 7.9 vs 9.4 ± 6.2, P = 0.804). In patients randomized to DB, esophageal acid exposure in a 2-hour window after the standardized meal on day 1 vs day 2 reduced from 11.8% ±6.4 to 5.2% ± 5.1, P = 0.015.

In patients with upright GERD, DB reduces the number of postprandial reflux events pressure by increasing the difference between LES and gastric pressure. These data further encourage studying DB as therapy for GERD.

Gastroesophageal reflux disease (GERD) is a prevalent, chronic medical condition that affects 13% of the adult population globally at least once a week. Sleep disturbances are frequently encountered in up to 25% of the GERD patients, likely due to nocturnal gastroesophageal reflux (GER). With advance in diagnostic techniques allowing for an improved understanding of involved physiological mechanisms of nocturnal reflux, there is growing evidence of a bidirectional relationship between GERD and sleep disturbances. Furthermore, nocturnal GER is associated with more complicated GERD. Obstructive sleep apnea (OSA) and GERD also have been linked, but to what degree remains controversial. Treatment of nocturnal GER has been shown to improve both subjective and objective sleep measures. The therapeutic approach includes lifestyle modifications and medication individualization and optimization with proton-pump inhibitors serving as the mainstay of treatment. Antireflux surgery and newer endoscopic procedures have been demonstrated to control nocturnal GER.

Intact esophageal mucosal integrity is essential to prevent symptoms during gastroesophageal reflux events. Approximately 70% of patients with heartburn have macroscopically normal esophageal mucosa. In patients with heartburn, persistent functional impairment of esophageal mucosal barrier integrity may underlie remaining symptoms. Topical protection of a functionally vulnerable mucosa may be an attractive therapeutic strategy. We aimed to evaluate esophageal mucosal functional integrity in patients with heartburn without esophagitis, and test the feasibility of an alginate-based topical mucosal protection.

Three distal esophageal biopsies were obtained from 22 patients with heartburn symptoms, and 22 control subjects. In mini-Ussing chambers, the change in transepithelial electrical resistance (TER) of biopsies when exposed to neutral, weakly acidic, and acidic solutions was measured. The experiment was repeated in a further 10 patients after pretreatment of biopsies with sodium alginate, viscous control, or liquid control "protectant" solutions.

Biopsy exposure to neutral solution caused no change in TER. Exposure to weakly acidic and acidic solutions caused a greater reduction in TER in patients than in controls (weakly acid -7.2% (95% confidence interval (CI) -9.9 to -4.5) vs. 3.2% (-2.2 to 8.6), P<0.05; acidic -22.8% (-31.4 to 14.1) vs. -9.4% (-17.2 to -1.6), P<0.01). Topical pretreatment with alginate but not with control solutions prevented the acid-induced decrease in TER (-1% (-5.9 to 3.9) vs. -13.5 (-24.1 to -3.0) vs. -13.2 (-21.7 to -4.8), P<0.05).

Esophageal mucosa in patients with heartburn without esophagitis shows distinct vulnerability to acid and weakly acidic exposures. Experiments in vitro suggest that such vulnerable mucosa may be protected by application of an alginate-containing topical solution.

Nighttime reflux has been demonstrated to be associated with a more aggressive presentation of gastroesophageal reflux disease (GERD). However, it has remained unknown until now if the difference in nighttime reflux between the different GERD groups is related to the distribution of intraesophageal pH level or duration of acid exposure.

To compare distribution of intraesophageal pH during nighttime between patients with erosive esophagitis (EE) versus those with nonerosive reflux disease (NERD).

Patients with heartburn symptoms at least 3 times per week were included in this study. Patients were not receiving any antireflux treatment. All patients underwent an upper endoscopy to determine if esophageal inflammation was present or absent. Subsequently, patients underwent ambulatory 24-hour esophageal pH monitoring. Only those with NERD and EE were included in this study. Nighttime period was defined as the time from the moment patients entered the bed to fall asleep and until they woke up the next morning. Distribution of intraesophageal pH during nighttime was generated using a special computer program that analyzed all registered pH measurements.

Nineteen patients were found to have NERD and 31 EE. Time in bed was not different between the 2 groups. The mean number of acid reflux events, mean reflux time pH<4, and mean % total time pH<4 during nighttime were significantly lower in the NERD group as compared with the EE group (13.05±4.6, 19.7±7.09, 3.6±1.2% vs. 25.44±4.4, 29.3±7.97, 5.3±1.5%, respectively, all P<0.05). Symptom index for EE was 43.8% versus 21% for NERD, P<0.05. Overall, the distribution of intraesophageal pH during nighttime was similar between NERD and EE patients for all pH ranges.

Patients with EE demonstrated a significantly higher nighttime esophageal acid exposure as compared with NERD, but the overall distribution of the acid exposure was similar between the 2 groups. This suggests that duration rather than intensity of nighttime intraesophageal acid exposure accounts for the difference between EE and NERD.

Nocturnal gastro-esophageal reflux causes heartburn and sleep disturbances impairing quality of life. Lifestyle modifications, like bed head elevation during sleep, are thought to alleviate the symptoms of gastroesophageal reflux. We tested the hypothesis that bed head elevation might decrease recumbent acid exposure compared to sleeping in a flat bed.

Patients of symptomatic nocturnal reflux and documented recumbent (supine) reflux verified by esophageal pH test entered the trial. On day 1, baseline pH was measured while the patient slept on a flat bed. Then patients slept on a bed with the head end elevated by a 20-cm block for the next 6 consecutive days from day 2 to day 7. The pH test was repeated on day 2 and day 7. Each patient acted as his own control.

Twenty of 24 (83.3%) patients with mean age of 36 ± 5.5 years completed the trial. The mean (± SD) supine reflux time %, acid clearance time, number of refluxes 5 min longer and symptom score on day 1 and day 7 were 15.0 ± 8.4 and 13.7 ± 7.2; P = 0.001, 3.8 ± 2.0 and 3.0 ± 1.6; P = 0.001, 3.3 ± 2.2 and 1.0 ± 1.2; P = 0.001, and 2.3 ± 0.6 and 1.5 ± 0.6; P = 0.04, respectively. The sleep disturbances improved in 13 (65%) patients.

Bed head elevation reduced esophageal acid exposure and acid clearance time in nocturnal (supine) refluxers and led to some relief from heartburn and sleep disturbance.

Studies in the United States have revealed that gastroesophageal reflux disease (GERD) patients often suffer from nocturnal symptoms, sleep disturbance, and impaired quality of life. In a large subset of patients, these symptoms persist in spite of acid suppressive therapy. The aim of the present study was to assess the prevalence of heartburn and associated sleep complaints and the response to standard medical therapy with pantoprazole in primary and secondary care esophagitis patients in Belgium. Questionnaires were provided to consecutive patients presenting to primary and secondary care physicians with esophagitis. The questionnaire evaluated the presence of typical reflux symptoms, alarm symptoms, risk factors, and sleep quality impairment as a result of reflux episodes. Results are shown as mean ± standard deviation and compared by Student's t-test or chi-square test. A total of 4061 primary and 5261 secondary care patients (50% female, mean age 53 ± 0.2 years, body mass index of 25.7 ± 0.1 kg/m(2) ) were recruited. Eighty-four percent of patients reported sleep disturbance attributable to nighttime reflux, including typical nighttime supine reflux symptoms (72%), difficulties to fall asleep (39%), waking up during the night (45%), morning fatigue (35%), and reflux symptoms when waking up in the morning (47%). Mild, moderate, or severe nighttime heartburn were reported by, respectively, 30, 35, and 12%, and these numbers were 26, 28, and 6% for nighttime regurgitation. Alcohol (19%), smoking (22%), higher esophagitis grades (grades 2, 3, and 4 in, respectively, 31, 7, and, 7%), alarm symptoms (27%), and more severe heartburn and regurgitation during daytime were all significantly associated with all dimensions of sleep disturbance (P < 0.0001). Obesity was only related to symptoms in supine position and when waking up (P < 0.0001). After 1.4 ± 0.0 months of treatment with pantoprazole, any sleep disturbance had improved in more than 75% of patients, with resolution of nighttime heartburn and regurgitation in, respectively, 75 and 83%. The majority of patients presenting with reflux symptoms and esophagitis in primary or secondary care experience nighttime heartburn and regurgitation, and sleep disturbance by nighttime symptoms is present in 84%. Smoking, alcohol use, higher grades of esophagitis, more severe typical reflux symptoms during daytime, and the presence of alarm symptoms are risk factors for GERD-related sleep disturbance. On standard therapy with pantoprazole, nighttime symptoms improved in more than 75%. These observations support a direct relationship between GERD and sleep disturbance.

Proton pump inhibitors (PPIs) are the most widely used drugs for treatment of gastroesophageal reflux disease. However, approximately 20% of patients with reflux esophagitis and 40% of those with nonerosive reflux diseases complain of troublesome symptoms, even during treatment with PPIs. In patients with reflux esophagitis, dose escalation and co-administration with a histamine H(2)-receptor antagonist are potential approaches, since the major cause of PPI resistance is incomplete suppression of gastric acid secretion. On the other hand, for patients with nonerosive reflux disease, switching from PPIs to pain modulators is often necessary for improvement of symptoms, since 25% of patients with nonerosive reflux disease have symptoms not caused by gastroesophageal acid reflux. Therapeutic approaches for PPI-resistant patients with reflux esophagitis and nonerosive reflux diseases are considered according to pathogenesis.

Ambulatory 24 h esophageal pH monitoring enables quantification of esophageal acid exposure and assessment of the temporal relationship between symptoms and acid reflux events. Analysis of pH monitoring is currently divided into upright and recumbent periods based on the patient's body position. However, in this Review, we demonstrate that physiologic studies have shown that sleep, and not recumbency, has a greater impact on gastroesophageal reflux during night-time. The physiologic studies are further supported by clinical trials demonstrating that gastroesophageal reflux characteristics during the recumbent-awake period are similar to those in the upright rather than the recumbent-asleep period. The introduction of the integrated pH monitoring and actigraphy data analysis program offers better separation of the recumbent-awake and recumbent-asleep periods. The physiologic studies and clinical trials, as well as the availability of a better tool to measure pH during sleep, support a paradigm shift in the analysis of pH monitoring data from body position (upright or recumbent) to state of consciousness (awake or asleep).

Gastroesophageal reflux disease (GERD) is the most common upper gastrointestinal disorder seen in the elderly. The worldwide incidence of GERD is increasing as the incidence of Helicobacter pylori is decreasing. Although elderly patients with GERD have fewer symptoms, their disease is more often severe. They have more esophageal and extraesophageal complications that may be potentially life threatening. Esophageal complications include erosive esophagitis, esophageal stricture, Barrett's esophagus and adenocarcinoma of the esophagus. Extraesophageal complications include atypical chest pain that can simulate angina pectoris; ear, nose, and throat manifestations such as globus sensation, laryngitis, and dental problems; pulmonary problems such as chronic cough, asthma, and pulmonary aspiration. A more aggressive approach may be warranted in the elderly patient, because of the higher incidence of severe complications. Although the evaluation and management of GERD are generally the same in elderly patients as for all adults, there are specific issues of causation, evaluation and treatment that must be considered when dealing with the elderly.

The pathogenesis of gastrointestinal reflux disease is multifactoral. Integral to the disease process is the refluxate itself. The characteristics and composition of the refluxate are dependent on several physiological variables. The refluxate may contain varying concentrations of acid, pepsin, gas, or contents of duodenal reflux (such as bile acid and pancreatic enzymes). Characteristics such as volume and proximal extent of the refluxate, and the chemical content of this refluxate can strongly influence the risk of symptom perception. Strong acid (pH<4) and duodeno-gastro-oesophageal reflux are also implicated in the development of mucosal damage in the form of oesophagitis, Barrett's metaplasia and oesophageal adenocarcinoma. The manifestation of disease, however, is not entirely reliant on the refluxate, which must be considered in the context of the genetic, environmental and psychological susceptibility of the individual.

Recent studies demonstrate a bidirectional relationship between gastroesophageal reflux disease (GERD) and sleep in which nighttime reflux leads to sleep deprivation and sleep deprivation can exacerbate GERD by enhancing perception of intraesophageal stimuli. Current treatment primarily focuses on reducing nighttime reflux, thus improving sleep quality. Future studies are needed to further explore the relationship between GERD and sleep and the potential of novel therapeutic options to interrupt the vicious cycle between them.

Concern has been expressed that antacid drugs increase the risk of esophageal and gastric adenocarcinomas.

This population-based case-control study recruited patients with incident esophageal adenocarcinoma (n = 220), gastric cardiac adenocarcinoma (n = 277), or distal gastric adenocarcinoma (n = 441) diagnosed between 1992 and 1997, and 1,356 control participants in Los Angeles County. Unconditional polychotomous multivariable logistic regression analyses were done to evaluate the association between antacid drug use and these cancers.

Among participants who took nonprescription acid neutralizing agents for >3 years, the odds ratio for esophageal adenocarcinoma was 6.32 compared with never users (95% confidence interval, 3.14-12.69; P(trend) < 0.01). Analyses stratified by history of physician diagnosed upper gastrointestinal (UGI) disorders revealed a greater increase in esophageal adenocarcinoma risk associated with nonprescription antacid use among persons with no UGI disorder than among those with an UGI disorder (homogeneity of trends P = 0.07). Regular use of nonprescription acid neutralizing agents was not associated with risk of adenocarcinomas of the gastric cardia or distal stomach. Regular use of prescription acid suppressive drugs was not associated with risk for any of these cancers.

We found risk of esophageal adenocarcinoma was greater among long-term nonprescription acid neutralizing drugs in participants without physician-diagnosed UGI conditions than among those with these conditions; this may represent self medication for undiagnosed precursor conditions or it may be that nonprescription acid neutralizing drugs, taken without limitation on amount used when symptoms are most intense, may permit alkaline bile reflux into the lower esophagus, thereby increasing esophageal adenocarcinoma risk.

Antisecretory therapies that raise intragastric pH provide the best healing of the esophageal mucosal damage that occurs in gastroesophageal reflux disease. Continuous maintenance therapy is also effective to reduce the likelihood of recurrence of esophagitis and control symptoms in the long term. Proton pump inhibitor (PPI) therapy is an effective approach for healing esophagitis and controlling symptoms. Endoscopic and surgical treatments may provide an option for patients who are refractory to PPIs in whom reflux has been clearly demonstrated. Long-term antireflux medication is often needed after surgical treatment because of persisting or recurrent pathologic reflux and symptoms. An alternative approach to controlling transient lower esophageal sphincter relaxations, such as the GABA-B agonists, deserves further study.

Gastroesophageal reflux disease is a highly prevalent chronic condition in Western populations. It has a profound effect on our society in terms of economic cost and quality of life. There have been major advances in understanding of disease pathogenesis over the last few years which are summarized in this article.

With improved understanding of gastroesophageal reflux disease, newer developments in diagnostic techniques have evolved. The proton pump inhibitor test has been formally described as one of the initial diagnostic tests. Other new tests include multiple channel impedance monitoring, bilirubin reflux monitoring, Barostat measurements and intraluminal ultrasounds which, along with other newer technologies, are described in this review.

The mechanisms involved in the pathogenesis of gastroesophageal reflux disease are complex and multifactorial. The lower esophageal sphincter pressure, the motility of the esophageal body and the stomach, the composition of the reflux material and the sensitivity or resistance of the esophageal mucosa to the reflux material are important factors involved in the pathogenesis of disease-related symptoms and lesions. Based on our improving understanding, novel diagnostic tools are available to improve investigation of the disease.

To achieve more potent and long-lasting acid suppression, omeprazole was administered for 7 days in 5 regimens: 10, 20, and 40 mg once daily (od), and 10 and 20 mg twice daily (bid), in 7 healthy Helicobacter pylori-negative CYP2C19 homozygous extensive metabolizers, and intragastric pH was continuously measured. The median intragastric pH and percent time pH > 4.0 for 24 hours increased dose dependently with 10, 20, and 40 mg od. Ten and 20 mg bid wre comparable to 20 and 40 mg od, respectively. Concerning percent time pH > 4.0 in the nighttime (20:00-8:00 hours), 20 mg bid was significantly superior to 40 mg od (P < .05). In 4 of the 5 regimens, all 7 subjects had nocturnal acid breakthrough, whereas with 20 mg bid it occurred in only 3. We concluded that, considering nighttime acid suppression, omeprazole 20 mg bid had the strongest effect.

Duodenogastroesophageal reflux (DGER) can greatly increase microscopic and macroscopic esophageal mucosal damage caused by acid. The aim of this study was simultaneously to assess the chemical composition of DGER by detecting bilirubin in the refluxate by means of Bilitec and describe its pH and physical properties by impedance monitoring, in order to prove that non-acid reflux and biliary reflux are two distinct phenomena.

Twenty patients with gastroesophageal reflux disease (GERD) with symptoms refractory to conventional proton-pump inhibitor (PPI) therapy or with atypical GERD symptoms were included in the study. All patients underwent upper gastrointestinal endoscopy and simultaneous Bilitec and intraeosophageal impedance (IIM) and pH monitoring. In the majority of patients (16/20), the tests were performed while assuming a standard PPI dose.

Pathological bilirubin exposure, as defined by intraesophageal bilirubin absorbance above 0.14 for more than 3.9% of the time, was present in 9 cases, 6 of them with normal values of non-acid reflux, as detected by IIM. A pathological non-acid reflux, as defined by an IIM showing a percentage time with non-acid reflux greater than 1.4%, was observed in 5 patients, 2 of whom had no pathological biliary reflux, as detected by Bilitec. No correlation was found between the two indices, as expressed by an r-value of -0.12 (p>0.05).

Our study confirms that biliary reflux and non-acid reflux as detected by Bilitec and by IIM, respectively, are two distinct phenomena that require different techniques in order to be assessed in humans.

Oesophageal acid exposure analysis is divided to upright and supine, based on the assumption that the supine-awake period is similar to the supine-asleep period. To determine if the principal acid-reflux characteristics of supine-awake are closer to supine-asleep or upright period. Patients with heartburn underwent an upper endoscopy and pH testing. The patients were instructed to carefully document their upright, supine-awake and supine-asleep periods. A total of 64 patients were enrolled into this study (M/F 35/29; mean age 52.4 +/- 13.3). The mean percentage total time pH <4, frequency of acid-reflux events (per h) and number of sensed reflux events was not different between upright and the supine-awake period (P = ns). In contrast, the mean percentage total time pH <4, frequency of acid-reflux events and number of sensed reflux events was significantly higher in both upright and supine-awake periods vs supine-asleep (4.3 +/- 6.9, 1.86 +/- 2.7 and 0.01 +/- 0.05, P < 0.0001, respectively). The principal characteristics of the acid-reflux events in the supine-awake period are closer to the upright period than to the supine-asleep period.

Tegaserod, a serotonin 5-hydroxytryptamine (5-HT)4 receptor agonist, is thought to stimulate intestinal secretions. The aim of the current study was to assess the effect of tegaserod vs placebo on salivary and esophageal protective factors in patients with gastroesophageal reflux disease (GERD).

This study was a randomized, double-blind, placebo-controlled, cross-over trial in 38 GERD patients treated with tegaserod 6 mg twice a day vs placebo. Salivary samples were collected basally and during mastication. In addition, in 32 GERD patients, salivary and esophageal secretions also were collected during infusion of NaCl, HCl/pepsin, and NaCl in a consecutive fashion using a specially designed esophageal catheter. Saliva and esophageal perfusates were assessed for the pH, volume, content of buffers, protein, mucin, epidermal growth factor (EGF), transforming growth factor alpha (TGFalpha), and prostaglandin E (PGE)2 and analyzed statistically.

Salivary flow rates during administration of tegaserod increased over corresponding values during both basal conditions (P < .01) and mastication (P < .001). The rate of secretion of salivary bicarbonate and nonbicarbonate buffers also increased in basal conditions (P < .001 and P < .01, respectively) and during mastication (P < .05 and P = .05). Salivary EGF increased during mastication (P < .05), whereas PGE2 and TGF alpha increased in basal conditions (P < .05 and P < .01). Esophageal perfusate volumes increased during administration of tegaserod in basal conditions (P < .05), whereas esophageal EGF secretion increased after mucosal exposure to HCl/pepsin and subsequent final perfusion with NaCl (P < .05).

Significant stimulatory impact of 5-HT4 agonist on several salivary protective factors as well as esophageal EGF secretion may have esophagoprotective implications in patients with GERD and may help to address new therapies in the future.

Investigations and technical advances have enhanced our understanding and management of gastroesophageal reflux disease. The recognition of the prevalence and importance of patients with endoscopy-negative reflux disease as well as those refractory to proton pump inhibitor therapy have led to an increasing need for objective tests of esophageal reflux. Guidelines for esophageal reflux testing are developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee and approved by the Board of Trustees. Issues regarding the utilization of conventional, catheter-based pH monitoring are discussed. Improvements in the interpretation of esophageal pH recordings through the use of symptom-reflux association analyses as well as limitations gleaned from recent studies are reviewed. The clinical utility of pH recordings in the proximal esophagus and stomach is examined. Newly introduced techniques of duodenogastroesophageal reflux, wireless pH capsule monitoring and esophageal impedance testing are assessed and put into the context of traditional methodology. Finally, recommendations on the clinical applications of esophageal reflux testing are presented.

The traditional approach to gastro-oesophageal reflux disease as a spectrum disease has recently been criticised and the distinct phenotypic presentations model has been proposed.

To evaluate the main pathophysiological characteristics of various gastro-oesophageal reflux disease presentations.

Oesophageal manometry and 24-h pH-monitoring were performed in a gastro-oesophageal reflux disease series collected in a 7-year period.

Four hundred and twenty-one subjects were studied. Mean total percentage acid reflux time was significantly higher in long-segment Barrett's oesophagus and in ulcerative oesophagitis than in all the other gastro-oesophageal reflux disease groups, whilst in short-segment Barrett's oesophagus results were quite similar to those found in non-erosive reflux disease and in erosive reflux disease. Patients with ulcerative oesophagitis and long-segment Barrett's oesophagus were older than all the other gastro-oesophageal reflux disease groups. The mean lower oesophageal sphincter pressure was significantly reduced in non-erosive reflux disease, erosive reflux disease, ulcerative oesophagitis, short-segment Barrett's oesophagus and long-segment Barrett's oesophagus as compared with functional heartburn and hypersensitive oesophagus and with controls.

In keeping with the spectrum model of gastro-oesophageal reflux disease, severity of acid reflux increases from non-erosive reflux disease through erosive reflux disease up to ulcerative oesophagitis and long-segment Barrett's oesophagus. Ulcerative oesophagitis and long-segment Barrett's oesophagus could represent an advanced step in the natural history of gastro-oesophageal reflux disease. Our results do not confirm the distinct phenotypic presentations hypothesis.

When patients with the typical reflux symptoms of heartburn, regurgitation, or both, undergo endoscopy, up to 75% will not have endoscopic oesophagitis or evidence of Barrett's oesophagus. These patients have been described as having endoscopic negative or, more commonly, non-erosive reflux disease (NERD). Patients without oesophagitis, but with a positive pH test, can be diagnosed with gastro-oesophageal reflux disease (GERD). Some experts also consider a response to proton pump inhibitor therapy as proof of GERD in a patient with the correct symptoms and a negative endoscopy. Patients with normal acid exposure, but who report symptoms with a majority of their reflux episodes documented during an ambulatory pH study, have also been considered to have NERD, although others have labelled them as having 'functional heartburn'. Finally, there are some patients who have reflux symptoms and respond to reflux therapy, but have no demonstrable reflux by either endoscopy or ambulatory reflux testing. Whether these patients are part of the GERD spectrum or have another diagnosis is not clear. It seems that the most widely used definition of functional disease (the Rome II criteria) would include these patients as having functional heartburn, as it was defined as 'greater than or equal to 12 weeks of either continuous or intermittent symptoms of burning retrosternal discomfort or pain without pathologic GERD, achalasia, or other motility disorders with a recognized pathologic basis'. This article reviews potential differences in pathophysiology between erosive oesophagitis and NERD; explores whether symptoms can help distinguish NERD patients from erosive oesophagitis patients; and explores the evaluation and therapy of these patients.

Proton-pump inhibitors are effective at preventing the acid component of gastro-oesophageal refluxate from entering the oesophagus. It is not clear whether proton-pump inhibitors prevent duodenogastro-oesophageal reflux.

To measure oesophageal exposure to duodenogastro-oesophageal refluxate while on proton-pump inhibitors in patients with Barrett's oesophagus.

Twenty-five patients (23 male) with Barrett's oesophagus underwent 24 h oesophageal pH and Bilitec 2000 monitoring while on omeprazole 40 mg/day (n = 19) or omeprazole 60 mg/day (n = 6). All patients were undergoing argon plasma ablation of their Barrett's epithelium as part of a clinical trial and the Bilitec measurements were only carried out after the ablation had been completed.

20 of 25 (80%) patients had a normal oesophageal pH profile. Fifteen of the 25 (60%) had abnormal oesophageal exposure to bile as measured by Bilitec 2000. Of the 20 patients who had a normal 24 h oesophageal pH profile, 11 (55%) had pathological exposure to bile in their oesophagus.

Complete acid suppression does not guarantee elimination of duodenogastro-oesophageal reflux.

Gastro-esophageal reflux disease (GERD) is a highly prevalent disease caused by the exposure of the esophagus to refluxed gastric contents. Proton pump inhibitors (PPIs) are the mainstay of current treatment. At present, the assessment of the efficacy of different PPIs in the treatment of GERD employs two measures: esophageal and gastric pH monitoring. Esophageal pH monitoring is the most accurate method of detecting reflux episodes and, therefore, its role as a diagnostic modality is well accepted. Gastric pH monitoring, on the other hand, is an accurate measure of gastric acid pH, but its relevance to patients with GERD is questionable, since recordings correlate poorly with esophageal acid exposure.

This paper reviews (based on a Medline literature search, 1980-2004) the clinical relevance of esophageal and gastric pH measurements in both the management of GERD and in the evaluation of the efficacy of PPI therapy.

Evidence presented suggests that the assessment of esophageal pH yields data of greater relevance to patients with GERD than does data from gastric pH. This largely arises from the fact that esophageal pH monitoring assesses the pH of the refluxate and the frequency of reflux episodes at the mucosal site affected by the disease. The use of esophageal pH monitoring is recommended in patients who fail to present with endoscopic evidence of esophagitis, those with extra-esophageal symptoms, those who have failed traditional anti-reflux therapies, and those who are potential candidates for anti-reflux surgery. In recent years, the technique has benefited from the development of a wireless pH probe, and there is also an increasing body of evidence supporting its use in combination with other emerging technologies, such as Bilitec monitoring and multichannel intraluminal impedance. Such an approach is anticipated to aid both the diagnosis of GERD and the characterization of gastro-esophageal reflux (GER) in these patients.

Symptoms of gastro-oesophageal reflux disease (GERD) range from mild to severe and, when they occur during night-time hours, can interfere with sleep patterns and reduce overall quality of life. The clinical presentation of GERD is characterized by oesophageal as well as supra-oesophageal symptoms, including otolaryngologic and pulmonary complications. However, GERD may be overlooked as the cause of a patient's supra-oesophageal symptoms because these complaints can occur in the absence of oesophageal symptoms or endoscopic changes. The role of available tools used for GERD diagnosis, including endoscopy, oesophageal pH monitoring and an empirical course of proton pump inhibitor therapy, is discussed. Interventions available to achieve the therapeutic goals of symptom relief and prevention include specific lifestyle modifications and over-the-counter as well as prescription pharmacological agents. Patient-initiated, as-needed treatment may not be the best choice for managing persistent night-time reflux because it requires patient arousal from sleep. Proton pump inhibitor therapy remains the treatment of choice for patients with more severe symptoms and those with erosive oesophagitis. Few studies have specifically evaluated the role of pharmacological agents in the management of night-time reflux and comparisons are difficult due to the variability in study design and endpoints assessed.

The pathogenesis of gastro-oesophageal reflux disease (GERD) is multifactorial, involving transient lower oesophageal sphincter relaxations (TLESRs) as well as other lower oesophageal sphincter (LES) pressure abnormalities. GERD is associated with a decrease in LES pressure, which can be provoked by factors such as foods (fat, chocolate, etc.), alcohol, smoking and medications. These factors have also been shown to increase TLESRs. As a result, reflux of acid, bile, pepsin and pancreatic enzymes occurs, leading to oesophageal mucosal injury, which can potentially progress to oesophageal adenocarcinoma in a minority of patients with Barrett's metaplasia. In addition, duodenogastric contents can also contribute to oesophageal injury. Other factors contributing to the pathophysiology of GERD include hiatal hernia, poor oesophageal clearance, delayed gastric emptying and impaired mucosal defensive factors. Hiatal hernia has a permissive role in the pathogenesis of reflux oesophagitis by promoting LES dysfunction. Delayed gastric emptying, resulting in gastric distension, can significantly increase the rate of TLESRs, contributing to postprandial GER. The mucosal defensive factors have an important role in GERD. When excessive acid causes a breakdown in oesophageal epithelial defenses, epithelial resistance may be reduced. Nocturnal GERD is associated with prolonged acid exposure and proximal extent of acid contact, which elevates the risk for oesophageal damage and GERD-related complications. In sum, GERD is a complex problem caused by many factors that are exacerbated when the patient is in the supine position.

The diagnosis and management of Barrett's esophagus (BE) are controversial. We conducted a critical review of the literature in BE to provide guidance on clinically relevant issues.

A multidisciplinary group of 18 participants evaluated the strength and the grade of evidence for 42 statements pertaining to the diagnosis, screening, surveillance, and treatment of BE. Each member anonymously voted to accept or reject statements based on the strength of evidence and his own expert opinion.

There was strong consensus on most statements for acceptance or rejection. Members rejected statements that screening for BE has been shown to improve mortality from adenocarcinoma or to be cost-effective. Contrary to published clinical guidelines, they did not feel that screening should be recommended for adults over age 50, regardless of age or duration of heartburn. Members were divided on whether surveillance prolongs survival, although the majority agreed that it detects curable neoplasia and can be cost-effective in selected patients. The majority did not feel that acid-reduction therapy reduces the risk of esophageal adenocarcinoma but did agree that nonsteroidal antiinflammatory drugs are associated with a cancer risk reduction and are of promising (but unproven) value. Participants rejected the notion that mucosal ablation with acid suppression prevents adenocarcinoma in BE but agreed that this may be an appropriate strategy in a subgroup of patients with high-grade dysplasia.

Based on this review of BE, the opinions of workshop members on issues pertaining to screening and surveillance are at variance with published clinical guidelines.

The reason why less than one-half of patients with gastro-oesophageal reflux disease develop complicated reflux disease (ulcerative oesophagitis, oesophageal strictures and Barrett's oesophagus) and erosive reflux oesophagitis is not fully understood. Supine nocturnal oesophageal acid reflux is considered to be critically involved in this phenomenon, but reliable data are lacking.

To clarify whether high levels of supine nocturnal oesophageal acid exposure are associated with complicated reflux disease.

Ambulatory 24-h oesophageal pH monitoring was performed in 220 patients with gastro-oesophageal reflux disease (56 with complicated reflux disease, 76 with erosive reflux oesophagitis and 88 with non-erosive reflux disease). The total, supine nocturnal and upright diurnal percentage acid reflux times were calculated.

The total percentage acid reflux time was significantly greater in complicated reflux disease than in either erosive reflux oesophagitis (P = 0.024) or non-erosive reflux disease (P = 0.000). These differences were entirely due to a greater supine nocturnal percentage acid reflux time (P = 0.038 and P = 0.000, respectively), whereas no difference was observed in the upright diurnal percentage acid reflux time.

Complicated reflux disease is characterized by high levels of supine nocturnal percentage acid reflux time. Prospective studies would be appropriate to clarify whether the normalization of this parameter is relevant to the effective management of this subset of patients with gastro-oesophageal reflux disease.

The reason why heartburn in gastro-oesophageal reflux disease subjects without oesophagitis is less responsive to proton pump inhibitors than heartburn in those with erosive oesophagitis is not known.

Gastric and oesophageal pH were determined in 26 subjects with gastro-oesophageal reflux disease at baseline and on days 1, 2 and 8 of treatment with 20 mg omeprazole or 20 mg rabeprazole in a randomized, two-way cross-over fashion. The presence or absence of erosive oesophagitis at baseline was documented by upper gastrointestinal endoscopy.

At a given value of the integrated gastric acidity during treatment with a proton pump inhibitor, the probability of pathological oesophageal reflux was significantly higher in subjects with no oesophagitis than in those with erosive oesophagitis. This occurred because the post-prandial gastric acidity in subjects with no oesophagitis showed a decreased response to the antisecretory agent.

Compared with gastro-oesophageal reflux disease subjects with erosive oesophagitis, those with no oesophagitis are relatively refractory to the pharmacodynamic effects of proton pump inhibitors on the post-prandial integrated gastric acidity.

In gastro-oesophageal reflux disease (GERD) subjects treated with a gastric anti-secretory agent, it is not known whether there is a relationship between heartburn severity and oesophageal acid exposure.

Oesophageal pH and heartburn severity were determined in 27 GERD subjects at baseline and on days 1, 2 and 8 of treatment with 20 mg omeprazole or 20 mg rabeprazole in a randomized, two-way crossover fashion.

Receiver operating characteristic (ROC) analysis was used to determine values for heartburn severity that gave optimal cut-off points for distinguishing between normal and pathologic oesophageal reflux. Using these cut-off points, we found that the probability of no pathologic oesophageal reflux (Y) could be best fitted by an exponential equation: Y = a(e-bX) + c, where a, b and c are constants and X is the value of heartburn severity. There was close agreement between predicted and observed percentages of subjects with pathologic oesophageal reflux during different days of treatment.

In GERD subjects treated with a proton-pump inhibitor, the value of heartburn severity following a single standard meal can predict the likelihood of pathologic oesophageal reflux over the entire 24-h period.

In subjects with gastro-oesophageal reflux disease treated with a gastric antisecretory agent, the extent to which gastric acidity needs to be reduced to prevent pathological oesophageal acid exposure is not known.

Gastric and oesophageal pH were measured in 26 healthy subjects and in 59 subjects with gastro-oesophageal reflux disease. In 27 of the subjects with gastro-oesophageal reflux disease, pH was also recorded on days 1, 2 and 8 of treatment with 20 mg omeprazole and 20 mg rabeprazole in a randomized, two-way, cross-over fashion.

Receiver operating characteristic analysis was used to determine values for the integrated oesophageal acidity and time oesophageal pH<or=4 that gave optimal cut-off points for distinguishing between normal and pathological oesophageal reflux. Using these cut-off points, we found that the probability of no pathological oesophageal reflux (Y) could be best fitted by an exponential equation, Y = a(e-bX) + c, where a, b and c are constants and X is the value of the integrated gastric acidity. There was close agreement between the predicted and observed percentages of subjects with pathological oesophageal reflux during different days of treatment.

In subjects with gastro-oesophageal reflux disease treated with a proton pump inhibitor, the value of the integrated gastric acidity can predict the likelihood of pathological oesophageal reflux.

Plasma concentration measurements have confirmed that the advantageous hepatic metabolism of esomeprazole results in a greater delivery of acid suppressant to the systemic circulation, compared with an equal dose of omeprazole. Also, this superior delivery has been shown to cause a more consistent and greater suppression of pentagastrin-stimulated gastric acid secretion by esomeprazole, 20 mg, compared with omeprazole, 20 mg. The superior acid-suppressant properties of esomeprazole have been revealed by extensive 24-h intragastric pH-monitoring studies. Compared with omeprazole, 20 mg, esomeprazole, 20 mg and 40 mg, has been shown to give superior outcomes on three key measures of antisecretory effect: (1) consistency amongst individuals; (2) duration over the 24-h cycle; (3) overall impact on pH. As there is a substantial increment of acid control from esomeprazole, 20 mg, to esomeprazole, 40 mg, this latter dose is the most appropriate to investigate for modern initial therapy of reflux disease, with the aim of achieving the highest possible response rates in the shortest possible time.

The more potent and longer-lasting inhibition of gastric acid secretion provided by proton pump inhibitors (PPIs) as compared with histamine-2-receptor antagonists is caused in large part by differences in their mechanism of action. PPIs block histamine-2-, gastrin-, and cholinergic-mediated sources of acid production and inhibit gastric secretion at the final common pathway of the H+/K+ adenosine triphosphatase proton pump. In contrast, histamine-2-receptor antagonists cannot block receptor sites other than those mediated by histamine. It seems that the rapid loss of acid suppression activity by the histamine-2-receptor antagonists may be attributed to tolerance. Such tolerance has not occurred in patients receiving PPIs because these agents are irreversible inhibitors of the H+/K+ adenosine triphosphatase proton pump. For these reasons, patients who have acid-related disorders that require high levels of acid suppression do not respond well to intravenous histamine-2-receptor antagonists and would be excellent candidates for intravenous PPI therapy. Candidates for intravenous PPIs also include patients who cannot receive oral PPIs and those who may need the higher acid suppression therapy provided by the intravenous rather than the oral route. Clinical studies have demonstrated the efficacy of intravenous pantoprazole in maintaining adequate control of gastric acid output during the switch from oral to intravenous therapy in patients with severe gastroesophageal reflux disease or the Zollinger-Ellison syndrome. Intragastric administration of solutions prepared from oral PPIs has been used as an alternative to the intravenous route in critical care settings. However, decreased bioavailability may limit the value of intragastric delivery of PPIs because of the high frequency of gastric emptying problems in critically ill patients.

To assess the oesophageal manometric characteristics and 24-h pH profiles of patients with both short-segment and long-segment Barrett's oesophagus and compare them with those of patients with reflux oesophagitis and controls.

Seventy-nine patients who had undergone upper digestive endoscopy were recruited: 16 had short-segment Barrett's oesophagus, 13 had long-segment Barrett's oesophagus, 25 had grade III oesophagitis according to the Savary-Miller classification and 25 were used as controls. The diagnosis of Barrett's oesophagus was based on the histological detection of specialized intestinal metaplasia, which extended < 3 cm into the oesophagus in patients with short-segment disease and > 3 cm in patients with long-segment disease. All subjects underwent oesophageal manometry and basal 24-h oesophageal pH monitoring.

The lower oesophageal sphincter pressure was significantly lower in patients with reflux oesophagitis and short-segment and long-segment Barrett's oesophagus than in controls (P=0.0004-0.0001), but there was no difference among the three reflux groups. The peristaltic wave amplitude of patients with long-segment Barrett's oesophagus was significantly lower than that of controls (P=0.002) and patients with short-segment Barrett's oesophagus (P=0.02), but was no different from that of patients with reflux oesophagitis. The percentage of non-propagated wet swallows was significantly higher in patients with reflux oesophagitis and short-segment and long-segment Barrett's oesophagus when compared with that of controls (P=0.0004-0.0001). The total percentage of time the oesophagus was exposed to pH < 4.0 was significantly higher in patients with reflux oesophagitis and short-segment and long-segment Barrett's oesophagus (P=0.0001) than in controls, and was higher in patients with long-segment disease than in those with short-segment disease (P=0.01).

Long-segment Barrett's oesophagus is characterized by a greater impairment of peristaltic wave amplitude and a higher oesophageal acid exposure than is short-segment Barrett's oesophagus. However, both forms are linked to increased acid reflux.

The acid inhibitory effect of lansoprazole depends on the S-mephenytoin 4'-hydroxylase (CYP2C19) genotype status. The effect of famotidine is independent of this genotype.

To investigate the acid inhibitory effects of lansoprazole vs. famotidine during the daytime and night-time with reference to different CYP2C19 genotypes.

Fifteen healthy volunteers were given 20 mg famotidine twice a day or 30 mg lansoprazole once a day for 8 days. On post-dose day 8, 24-h intragastric pH monitoring was performed.

During the daytime, the intragastric pH with lansoprazole was significantly higher than that with famotidine in the heterozygous extensive metabolizer group, whereas no significant difference was observed in the homozygous extensive metabolizer group. During the night-time, the intragastric pH with famotidine was quite similar to that with lansoprazole in the heterozygous extensive metabolizer and poor metabolizer groups. However, during the night-time, the intragastric pH with famotidine was significantly higher than that with lansoprazole in the homozygous extensive metabolizer group.

An insufficient acid inhibition by lansoprazole during the night-time in the homozygous extensive metabolizer group could be compensated for by famotidine. CYP2C19 genotype testing appears to be useful for predicting the optimal acid inhibitory drug treatment collated with circadian intragastric pH change.

Integrated gastric and oesophageal acidity can be calculated from measurements of gastric and oesophageal pH and used to quantify gastric and oesophageal acidity over time. Rabeprazole is a new proton pump inhibitor that is effective in treating gastro-oesophageal reflux disease (GERD).

To use measurement of integrated gastric and oesophageal acidity to determine the onset, duration and overall effect of rabeprazole in subjects with GERD.

Subjects with GERD were required to have oesophageal pH less-than-or-equal 4 for at least 10% of a 24-h recording. Effects of 20 mg rabeprazole on 24-h gastric and oesophageal pH were measured on days 1 and 7 of dosing. Integrated gastric and oesophageal acidity were calculated from time-weighted average hydrogen ion concentrations at each second of the 24-h record.

At steady-state, 20 mg rabeprazole inhibited gastric acidity by 89% and oesophageal acidity by 95%. The first dose of rabeprazole inhibited gastric and oesophageal acidity by at least 70% of the steady-state effect. Oesophageal acidity could be divided into monophasic and biphasic patterns, and rabeprazole had different effects on oesophageal and gastric acidity in these two GERD subpopulations. The onset of action of the first dose of rabeprazole on gastric acidity was 4 h and on oesophageal acidity was 4 h in monophasic subjects and 7 h in biphasic subjects. Integrated acidity was more sensitive than time pH less-than-or-equal 4 in measuring the inhibitory actions of rabeprazole.

Integrated gastric and oesophageal acidity are quantitative measurements that provide useful and novel information regarding the pathophysiology of GERD as well as the impact of antisecretory agents such as rabeprazole.

To determine the relationship between Barrett's esophagus (BE) and features of gastroesophageal acid reflux, 24 h esophageal pH monitoring was performed in 90 patients. The patients were divided into 3 groups: 31 subjects with BE, 21 with mild esophagitis and 38 with severe esophagitis. The following parameters were evaluated: the percentage time of pH < 4; the number of reflux episodes over 5 min; the duration of longest episodes and DeMeester score over total period and the auterior three parameters in erect and supine position. All these parameters in BE were significantly different from those with mild esophagitis (P < 0.01) and not significantly different from those with severe esophagitis (P > 0.05). During supine position all the above parameters in BE were significantly different from those with reflux esophagitis (P < 0.05). It is concluded that the quantity of acid reflux is not an important factor in development of BE in gastroesophageal reflux (GER), and the acid reflux in supine position might be important in development of BE in GER.

Postural measures are early recommendations in the management of heartburn, and are aimed at preventing acid reflux through an incompetent lower esophageal sphincter (LES). However, LES incompetence is found in only a minority of patients, and transient LES relaxations, primarily in the upright position, are currently recognized as the main pathophysiological abnormality in gastroesophageal reflux disease (GERD). We investigated the importance of supine acid reflux in patients with GERD.

Upon review of their clinical, manometric, pH monitoring and endoscopic characteristics, 85 patients with reflux symptoms were classified into three groups: Group A (n=22), consisting of symptomatic patients without esophagitis or pathological reflux; group B (n=38), symptomatic patients with reflux but no endoscopic esophagitis; and group C (n=25), symptomatic patients with both ulcerative or complicated esophagitis and pathological reflux.

All groups were similar in age distribution. Groups B and C had a higher prevalence of hiatal hernia and reflux symptoms. Manometry revealed similar LES pressures in groups A and B, but lower LES pressure in group C (P < 0.005). In groups A and B, supine reflux, in terms of percentage of time with pH < 4, was less pronounced than upright reflux (P < 0.0001). In contrast, group C supine reflux was as pronounced as the upright reflux.

The majority of patients reflux in the upright position. Only patients with complicated esophagitis have significant bipositional acid reflux. These findings suggest that unless the patient has severe reflux disease, postural measures may not be indicated.

The aim of this study was to demonstrate that integrated esophageal and gastric acidity values, calculated from 24-h pH recordings, can provide more precise quantitative temporal data than the conventional pH parameters historically associated with gastroesophageal reflux disease (GERD) investigations.

Esophagogastroduodenoscopy results and pH tracings from 20 GERD subjects with > or =10% esophageal acid contact time were studied. Integrated gastric and esophageal acidity were calculated from time-weighted average hydrogen ion concentrations at each second of the 24-h recording period.

Integrated esophageal acidity correlated with grade of esophagitis. Two quite distinct GERD subtypes were identified, with either a monophasic or biphasic pattern of integrated esophageal acidity. "Biphasic" subjects differed from "monophasic" subjects in terms of magnitude and pattern of integrated esophageal acidity. Although both groups had significant integrated nocturnal gastric acidity, only the biphasic GERD subjects had concomitant increases in nocturnal integrated esophageal acidity. Esophagitis grade was correlated with magnitude rather than pattern of integrated esophageal acidity, and it was possible to calculate a reflux coefficient that seems to provide an estimate of the quantitative motor disturbance present in GERD.

Integrated esophageal and gastric acidity provide quantitative measures of GERD pathophysiology and, compared to conventional pH parameters, should enhance evaluation of therapeutic interventions.

The role of acid in the pathogenesis of gastro-oesophageal reflux disease (GERD) has been extensively studied and is well accepted. The role, if any, of non-acid reflux, in particular duodenogastro-oesophageal reflux, is much debated. The availability of new technology to detect non-acid reflux has heightened interest in this question. This article reviews the following: How do we define non-acid reflux? Does duodenogastro-oesophageal reflux (alone or in combination) cause oesophageal injury, symptoms or both? What is its role in complicated GERD? What methods are available to assess non-acid reflux? Does non-acid reflux need treatment and if so what modalities are available?

Nocturnal gastric acid breakthrough is defined as night-time periods when gastrin pH falls below 4.0 for greater than 1h during administration of a proton pump inhibitor. This phenomenon is a serious problem for patients who require strict control of their gastric acid secretions.

To investigate the prevalence of nocturnal gastric acid breakthrough in Japanese subjects during administration of rabeprazole, and to clarify the relationship between Helicobacter pylori infection and nocturnal gastric acid breakthrough.

Thirty-one normal male volunteers were examined by ambulatory 24 h gastric pH monitoring four times: without medication, after a morning or an evening dose of 20 mg rabeprazole, and after administration of an H2-receptor antagonist at bedtime, in addition to the morning dose of rabeprazole. H. pylori infection was determined by the 13C-urea breath test and an assay for serum anti-H. pylori antibody.

Nocturnal gastric acid breakthrough was observed in 12 patients (39%) after the morning dose of 20 mg rabeprazole. In all cases, nocturnal gastric acid breakthrough was inhibited completely by administration of the H2-receptor antagonist at bedtime. Only one patient with nocturnal gastric acid breakthrough had H. pylori infection.

The absence of H. pylori infection appears to be closely related to the occurrence of nocturnal gastric acid breakthrough during dosing with a proton pump inhibitor.

Better control of gastric acid secretion with omeprazole appeared to decrease the need for dilatation of oesophageal strictures complicating gastro-oesophageal reflux disease in our hospital-based endoscopy service.

To investigate whether the perceived decrease in the need for oesophageal dilatation could be documented from endoscopy records, and, if confirmed, whether this could be related to the treatment used.

Retrospective study of the records of 69 patients who had peptic oesophageal strictures dilated, followed by treatment with acid inhibition for at least 6 months. Mean duration of follow-up was 3.9 years during treatment with H2-receptor antagonists and 2.1 years while on omeprazole (258 and 78 patient-years, respectively). Re-dilatation rates were compared between those treated with H2-receptor antagonists or omeprazole.

There has been a significant decrease in dilatations performed for gastro-oesophageal reflux induced strictures (P<0.001), while dilatation rates for other indications remained constant. Treatment with omeprazole not only decreased the need for further dilatations, but also prolonged the mean time between any further dilatations to 26.3 months compared to 9.3 months for those on an H2-receptor antagonist (P<0.0001).

Following dilatation of peptic oesophageal strictures, treatment with omeprazole in place of an H2-blocker significantly decreases the need for repeat dilatation.

In normal subjects, transient lower oesophageal sphincter relaxations (TLOSRs) and gas reflux during belching are suppressed in the supine position. Supine reflux, however, is a feature of reflux disease.

To investigate whether postural suppression of TLOSRs and gas reflux is impaired in patients with reflux disease.

Ten patients with erosive oesophagitis.

Oesophageal manometry was performed during gastric distension with 750 ml carbon dioxide. Measurements were made for 10 minutes before and after distension in both sitting and supine positions.

In the sitting position gastric distension substantially increased the rate of gas reflux (median (interquartile range)), as evidenced by increases in oesophageal common cavities from 1 (0-1)/10 min to 7 (5-10)/10 min and TLOSRs from 1 (1-1.5)/10 min to 6 (2.5-8)/10 min. However, this effect was suppressed in the supine position in all but one patient (TLOSRs 0 (0)/10 min to 1 (0-4.5)/10 min, common cavities 0 (0)/10 min to 0.5 (0-2)/10 min).

Postural suppression of TLOSRs and gas reflux is generally preserved in reflux disease.

On chronic intake of omeprazole, most healthy volunteers and patients still have nocturnal acid breakthrough (NAB), defined as night-time periods with gastric pH < 4.0 lasting for longer than 1 h. Gastro-oesophageal reflux during NAB may be particularly injurious to the oesophageal mucosa, contributing to the chronic lesions complicating the condition.

To compare the effect of three different dosing regimens of omeprazole 40 mg daily with regard to suppressing nocturnal gastric acidity and avoiding NAB.

Eighteen healthy volunteers were given three different regimens of omeprazole for 7 days each in randomized order: 40 mg before breakfast (qAM), 40 mg before dinner (qPM) and 20 mg before breakfast and dinner (b.d.). On day 7, 24-h intragastric and intraoesophageal pH-metry was performed. Tracings were analysed for the period from 22.00 h until 06.00 h with regard to the percentage of time at which gastric pH was below 4.0, 3.0 and 2.0, and also the occurrence and duration of NAB.

Nocturnal acid breakthrough was significantly more common on qAM than on qPM and b.d. (P < 0.05) dosing. The percentage of time gastric pH was less than 4.0 overnight was significantly lower on qPM (median 31.3) and b.d. (median 20.5) than on qAM (median 66.3) dosing (P=0.01 and P < 0.02, respectively). A pH threshold of 3 and 4 showed the same differences, as did median 24-h gastric pH. Daytime acidity was not significantly different.

In healthy volunteers, dinner time or split dosing of omeprazole 40 mg daily is significantly more effective than dosing before breakfast in preventing NAB and controlling gastric acidity. These regimens should be preferred in patients in whom suppression of nocturnal gastric acidity is desirable.