Non-erosive Gastroesophageal Reflux Disease Research Articles

Evaluation Of Safety And Efficacy Of Pantoprazole And Domperidone Combination In Patients With Gastroesophageal Reflux Disease

Background: Gastro-esophageal reflux disease (GERD) and non ulcer dyspepsia (NUD) are overlapping disorders with common symptomatology. The combination is synergistic by decreasing acid production as well as increasing lower esophageal tone & esophageal clearance thus producing a better therapeutic response. Objective: To evaluate the safety and efficacy of the combination Methods: In patients satisfying the inclusion and exclusion criteria for GERD (Group A, n=105) and Non Erosive GERD (Group B, n=19) baseline symptomatology, endoscopy & laboratory investigations were done followed by test medication once daily for 28 days & monitored for symptom improvement at week 1, 2, & 4 and endoscopy and laboratory investigations at week 4. Results: Of Group A patients having erosive GERD 68/94 (72.34%) were completely cured, 19/94 (20.21%) partially cured, 7/94 (7.44%) not cured. All patients having Non-Erosive GERD had significant improvement in symptoms at 4 week from baseline. Conclusion: Combination of pantoprazole and domperidone is a effective & safe combination with high symptom improvement rates.

Association Between Dinner-to-Bed Time and Gastro-Esophageal Reflux Disease

It is generally recommended that patients with gastro-esophageal reflux disease (GERD) refrain from eating within 3 h of going to sleep. In addition to a remarkable lack of supporting clinical evidence, whether GERD patients have shorter dinner-to-bed time is unknown. This study was designed to determine a possible association between dinner-to-bed time and GERD, compared with healthy adults. In a matched case-control study, we enrolled 147 GERD patients, and age- and sex-matched 294 controls without GERD symptoms such as heartburn and acid regurgitation during the previous year. Dinner-to-bed time, defined as the time intervals until going to bed after finishing eating dinner, was examined by a self-report questionnaire. Logistic regression was used to calculate odds ratio (OR) and 95% confidence intervals (CI) for GERD. After adjustment for smoking habits, drinking habits, and body mass index, shorter dinner-to-bed time was significantly associated with an increased OR of GERD (p < 0.0001) and the OR for patients whose dinner-to-bed time was less than 3 h was 7.45 (95% CI 3.38-16.4) compared with patients whose dinner-to-bed time was 4 h or more. These observations were consistent in both patients with non-erosive GERD and erosive esophagitis, and there was no significant difference in dinner-to-bed time intervals between non-erosive GERD and erosive esophagitis. In this matched case-control study, shorter dinner-to-bed time was significantly associated with an increased OR for GERD.

Efficacy of Rabeprazole in the Treatment of Symptomatic Gastroesophageal Reflux Disease

The purpose of this study was to assess the rapidity of symptom relief and 4-week efficacy of rabeprazole 20 mg in patients with moderately severe nonerosive gastroesophageal reflux disease. Data were analyzed from 2 similarly designed, double-blind, placebo-controlled, multicenter, U.S. trials. After a 2-week placebo run-in period, patients (N = 261) were randomized to 4 weeks of rabeprazole 20 mg once daily or placebo. Patients kept symptom diaries and scored symptom severity. Median time to first 24-hour heartburn-free interval was 3.5 days for the rabeprazole group compared with 19.5 days for the placebo group (P < or = .0002). Complete heartburn relief at week 4 was 32% with rabeprazole and 3.8% with placebo (P < or = .001). Rabeprazole also significantly improved other GERD-associated symptoms (e.g., regurgitation, belching, early satiety) by week 4 compared with placebo (P < or = .05). Rabeprazole provides fast and potent relief from heartburn and other symptoms of nonerosive gastroesophageal reflux disease.

An Exploratory Open Label Trial of Tegaserod in Non-Erosive GERD Patients with Incomplete Response to PPIʼs

Purpose: Forty to 50% of patients treated with PPI's for non-erosive GERD (NERD) have persistent upper gastrointestinal symptoms. A previous study has shown that tegaserod improves variables of mechanical hypersensitivity and symptoms in patients with functional heartburn, suggesting tegaserod may be useful in symptomatic NERD. Aim: To determine if addition of tegaserod (6mg BID) to a prescribed PPI regimen improves: (1) Global GERD assessments and (2) occurrence, frequency, severity and distress of 10 upper gastrointestinal symptoms. Methods: This 4-week open-label, randomized, two-center, parallel-group pilot study followed a 4-week screening and 2-week baseline period. NERD patients on stable PPI's for at least 30 days with persistent symptoms were eligible. Treatments were: PPI + tegaserod 6 mg bid (Teg) or PPI alone in a 2:1 allocation. Patients completed weekly and end of treatment global symptom assessments. A GERD Symptom Assessment Questionnaire (GSAQ) was completed at screening and after treatment. A Global Composite Index Score (GCIS) was calculated from the GSAQ. Within-treatment changes from baseline were evaluated using paired t-tests. Between treatment comparisons employed analyses of covariance for continuous parameters, van Elteren's test for ordinal parameters, and Cochran-Mantel-Haenszel tests for dichotomous parameters. Results: Forty-one patients were evaluated (Age 21–63 yrs; 20 Males, 21 Females; n = 27 Teg + PPI; n = 14 PPI). Between treatment comparisons of global GERD assessments vs. pre-study were significant for Teg + PPI at week 1 (p = 0.02) and week 3 (p = 0.03). Occurrence of heartburn/acid reflux, regurgitation, abdominal bloating and nausea were improved at the final visit by Teg + PPI vs PPI alone (all p < 0.05). Frequency, severity and bothersomeness of regurgitation and nausea were improved at the final visit by Teg + PPI vs PPI alone (all p < 0.05). Teg+ PPI improved the GCIS from baseline to the final visit (p = 0.0002). Tegaserod was well tolerated, with no serious adverse events reported. Conclusions: Tegaserod in combination with a PPI significantly improved several global and individual symptom assessments in NERD patients with incomplete relief from PPI's. Data from this trial justifies investigation of the potential utility of tegaserod in patients with NERD.

Functional oesophageal epithelial defense against acid

Functional oesophageal epithelial defense, including cell proliferation, restitution, buffers and ion transporters, plays a significant role in maintaining mucosal integrity and enabling rapid repair after injury. Growth factors such as epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF) are associated with oesophageal epithelial proliferation or restitution. Na+/H+ exchanger-1, an ion transporter, regulates intracellular pH and cell volume, and may have roles in cell proliferation, migration and survival. Cytokine, adhesion molecules, cyclooxygenase-2 and free radicals are associated with oesophageal inflammation and breach of the functional epithelial defense. Although the oesophagus does not have strong functional epithelial defense against acid, this defensive mechanisms may be involved in the pathogenesis of non-erosive gastro-oesophageal reflux disease. Medical therapy may be developed in future to enhance functional oesophageal epithelial defense.

Daily treatment with esomeprazole is superior to that taken on‐demand for maintenance of healed erosive oesophagitis

On-demand therapy with esomeprazole is effective for long-term treatment of non-erosive gastro-oesophageal reflux disease, but it has not been evaluated in erosive gastro-oesophageal reflux disease. To compare endoscopic and symptomatic remission over a 6-month period when patients with healed erosive gastro-oesophageal reflux disease are treated with esomeprazole 20 mg, either once daily or on-demand. Patients with verified erosive reflux oesophagitis of Los Angeles grades A-D were enrolled. Following 4-8 weeks treatment with esomeprazole 40 mg daily, those who were endoscopically healed and had symptom control during the last week were randomized to maintenance therapy for 6 months with esomeprazole 20 mg, taken either once daily or on-demand. Of 539 enrolled patients, 494 (91%) were healed at 8 weeks and 477 were randomized to maintenance therapy with esomeprazole 20 mg, 243 once daily and 234 on-demand. After once daily treatment, 81% of patients were still in remission at 6 months, compared with only 58% who took on-demand treatment (P < 0.0001). A difference in remission was found irrespective of baseline grade of oesophagitis, but it was more pronounced for the more severe grades. There was no difference in overall symptomatic remission between the two treatments, although heartburn was significantly more prevalent in the on-demand group. Once daily esomeprazole 20 mg was better than that taken on-demand for maintaining healed erosive oesophagitis, regardless of baseline Los Angeles grade.

Efficacy of famotidine and omeprazole in healing symptoms of non‐erosive gastro‐oesophageal reflux disease: randomized‐controlled study of gastro‐oesophageal reflux disease

The epidemiology and pathophysiology of non-erosive gastro-oesophageal reflux disease differs from erosive gastro-oesophageal reflux disease. There is a possibility that non-erosive gastro-oesophageal reflux disease treatment requires a different regimen/approach but it is not yet acknowledged. To investigate the efficacy of famotidine and omeprazole in the treatment of gastro-oesophageal reflux disease, especially non-erosive gastro-oesophageal reflux disease. A randomized, open-label trial was conducted. Fifty-four gastro-oesophageal reflux disease patients were assigned to treatment with famotidine at a dosage of 20 mg twice daily; or omeprazole, 20 mg once daily, for a period of 8 weeks. The Short Form-36 Health Survey and Gastrointestinal Symptom Rating Scale administered at baseline and after 8 weeks of treatment as well as a symptom questionnaire were conducted daily. Short Form-36 revealed that gastro-oesophageal reflux disease has severe impact on health-related quality of life. Thirty-nine subjects (77%) were endoscopically diagnosed as non-erosive gastro-oesophageal reflux disease. The mean Gastrointestinal Symptom Rating Scale abdominal pain, and indigestion score of non-erosive gastro-oesophageal reflux disease significantly improved in famotidine-treated patients (P < 0.05), but not in the omeprazole. There was no significant change regarding improved heartburn symptoms of non-erosive gastro-oesophageal reflux disease between treatments in the daytime or night-time. Famotidine and omeprazole were both effective in improving symptoms of gastro-oesophageal reflux disease, particularly non-erosive gastro-oesophageal reflux disease.

Famotidine vs. omeprazole: a prospective randomized multicentre trial to determine efficacy in non‐erosive gastro‐oesophageal reflux disease

Several studies in Western countries showed that proton-pump inhibitors are superior to histamine2-receptor antagonists or placebo in the treatment of non-erosive gastro-oesophageal reflux disease. The efficacy of acid-suppressive drugs for non-erosive gastro-oesophageal reflux disease in Japan, in which the prevalence of Helicobacter pylori infection is higher compared with Western countries, is unknown. To compare the efficacy of famotidine and omeprazole in Japanese patients with non-erosive gastro-oesophageal reflux disease by a prospective randomized multicentre trial. A total of 98 patients received either famotidine 20 mg b.d. (n = 48) or omeprazole once daily (n = 50). Frequency of gastro-oesophageal reflux disease symptoms and health-related quality of life were evaluated at baseline and after 4 weeks of treatment. Complete relief was defined as no gastro-oesophageal reflux disease symptoms during the 7-day interval in week 4. Complete relief was achieved in 23 (48%) of patients receiving famotidine and 28 (56%) of patients treated with omeprazole. In the famotidine group, complete relief rate in H. pylori-negative patients was significantly lower than H. pylori-positive patients (35% vs. 64%). Both famotidine and omeprazole improved most scales of health-related quality of life. Omeprazole significantly improved reflux score irrespective of H. pylori infection while famotidine significantly improved reflux score in H. pylori-positive patients but not in H. pylori-negative patients. Omeprazole is more effective than famotidine for the control of gastro-oesophageal reflux disease symptoms in H. pylori-negative patients, while similar efficacy is observed in H. pylori-positive patients with non-erosive gastro-oesophageal reflux disease.

Systematic review: the efficacy of intermittent and on‐demand therapy with histamine H2‐receptor antagonists or proton pump inhibitors for gastro‐oesophageal reflux disease patients

To perform a systematic review on the efficacy of intermittent and on-demand therapy with either histamine H2-receptor antagonists or proton pump inhibitors for patients with erosive oesophagitis or symptomatic heartburn. We conducted randomized-controlled trials of non-continuous therapy in gastro-oesophageal reflux disease patients. Fourteen studies met inclusion criteria. Because of variation in outcome measures statistical pooling of results was not possible. Results were analysed qualitatively. Four studies evaluated intermittent therapy of treatment 3 days a week with omeprazole 20 mg or daily with ranitidine which were not efficacious compared to a daily proton pump inhibitor. Famotidine 10 and 20 mg, ranitidine 75 mg and cimetidine 200 mg were efficacious in five on-demand studies for relief of symptomatic heartburn episodes. In three of four studies, evaluating only non-erosive (endoscopy-negative) gastro-oesophageal reflux disease patients, esomeprazole 20 and 40 mg and omeprazole 10 and 20 mg a day were efficacious using willingness to continue as an endpoint. Lansoprazole 30 mg and omeprazole 20 mg maintained symptom control in 60-70% of healed oesophagitis patients. Intermittent proton pump inhibitor or H2-receptor antagonist therapy is not effective in maintaining control in oesophagitis patients. H2-receptor antagonists are effective for relief of heartburn episodes. On-demand proton pump inhibitor therapy may work in a proportion of non-erosive gastro-oesophageal reflux disease patients.

Idiopathic dyspepsia

Idiopathic dyspepsia refers to pain and/or discomfort perceived in the epigastrium that is not secondary to organic, systemic, or metabolic diseases. Symptoms may overlap with those of gastroesophageal reflux disease and irritable bowel syndrome. Gastrointestinal motor disorders, hypersensitivity to mechanical or chemical stimuli, and psychosocial factors can act individually or in concert to induce the symptoms of dyspepsia. Accordingly, there is no single therapy, and treatment must be individualized. Eradication of Helicobacter pylori infection rarely achieves symptom improvement. Treatment of idiopathic dyspepsia should begin by reassuring the patient about the benign nature of the syndrome and educating them on the knowledge that has been achieved in recent years regarding potential causes of the syndrome. Both prokinetic and antisecretory drugs have been reported to improve dyspeptic symptoms, but results are not completely convincing. Although well-designed studies demonstrate superiority of proton pump inhibitors over placebo, it should be noted that patients with nonerosive gastroesophageal reflux disease were invariably included; when these patients are excluded, the benefit of antisecretory medications is questionable. We suggest that patients with idiopathic dyspepsia be initially treated according to the predominant symptom. Those with epigastric pain/burning should receive a trial with standard doses of proton pump inhibitors for 4 to 8 weeks, whereas prokinetic patients should be prescribed at recommended doses for similar periods of time to patients with nonpainful dyspeptic symptoms such as posprandial fullness, early satiety, nausea, or vomiting. Nonresponders may benefit from combination therapies or short trials with higher doses of drugs. Visceral analgesics and antidepressants can also be prescribed alone or in combinations with other therapeutic strategies. Recent studies demonstrate utility for psychologic therapy and hypnotherapy, although truly controlled studies are difficult in this area. Herbal medicines deserve further evaluation.

Efficacy and Safety of Lansoprazole in Adolescents with Symptomatic Erosive and Non‐erosive Gastroesophageal Reflux Disease

To assess the efficacy and safety of lansoprazole in the treatment of adolescents with symptomatic, endoscopically proven, non-erosive gastroesophageal reflux disease and erosive esophagitis. Adolescents between 12 and 17 years of age with esophagitis were enrolled in this open-label trial and treated with lansoprazole 15 mg (non-erosive) or 30 mg (erosive) once daily for 8 weeks. If unhealed at week 8, those with erosive esophagitis were treated with an additional 4 weeks of lansoprazole 30 mg once daily. Lansoprazole produced a significant reduction from baseline in the median percentage of days with reflux symptoms (91 to 43% in the 64 adolescents with non-erosive disease and 85 to 16% in the 23 adolescents with erosive esophagitis, P < or = 0.001 for each comparison). At week 8, mucosal healing had occurred in 95% (21 of 22) of those with erosive esophagitis. Treatment-related adverse events were reported by 19% of patients with non-erosive and 4% of patients with erosive esophagitis. Headache (7%), abdominal pain (5%), nausea (3%) and dizziness (3%) were the most frequently reported adverse events. One patient discontinued treatment early because of dizziness and vomiting. An elevation in mean serum gastrin from baseline (59 pg/mL at pretreatment to 80 pg/mL at final visit) was observed. Lansoprazole 15 mg or 30 mg once daily reduced symptoms of gastroesophageal reflux in adolescents with non-erosive gastroesophageal reflux disease and erosive esophagitis, respectively. Lansoprazole 30 mg once daily for 8 weeks was effective in healing erosive esophagitis. Both treatment regimens were considered safe.

Ineffective Esophageal Motility in Gastroesophageal Erosive Reflux Disease and in Nonerosive Reflux Disease

In GERD patients, ineffective esophageal motility (IEM), a hypocontractile disorder, is the most common motor abnormality. IEM has been associated with reflux in both the supine and upright position, prolonged esophageal clearance, and delayed of bolus transport. IEM has been equally present in erosive and in nonerosive GERD. Considering that reflux has been found to be more severe in erosive GERD than in nonerosive GERD patients and that IEM delays esophageal clearance, our hypothesis is that patients with erosive GERD have more severe IEM than those with nonerosive disease. A retrospective review of consecutive manometries of patients with the chief complaint of heartburn and a diagnosis of IEM were performed, and patients with both erosive and nonerosive GERD were selected. According to the number of ineffective contractions, IEM was stratified into three groups: 30% to 40%, mild; 50% to 60%, moderate; and greater than 60%, severe. We also registered the number of low amplitude, failed, and normal waves in each manometry of both groups. We evaluated 110 patients: 70 (64%) with erosive GERD and 40 (36%) with nonerosive GERD. The percentage of mild, moderate and severe IEM was similar in erosive and in nonerosive GERD patients, as well the number of low amplitude, failed or normal waves (P < 0.5). There were no differences between the severity of IEM in erosive and in nonerosive GERD patients.

Oesophageal intraluminal impedance can identify subtle bolus transit abnormalities in patients with mild oesophagitis

In a subgroup of patients with non-erosive gastroesophageal reflux disease (GORD) or mild oesophagitis, acid clearance is prolonged in spite of favourable gravity and normal or minimally impaired oesophageal peristalsis. Dysphagia is rare in this group but might also be present or develop after anti-reflux surgery. The causal relationship between prolonged clearance or dysphagia and oesophageal body dysmotility in these patients is not completely clear. New techniques are now available to assess oesophageal motility and transit and might help to detect more subtle defects underlying functional impairment in patients with GORD. Combined video-fluoroscopy and intraluminal impedance indicate an excellent correlation between both methods in detecting oesophageal bolus transit. Combined intraluminal impedance and manometry has the capability to evaluate oesophageal contractions and bolus transit without the use of radiation. Subtle bolus transit abnormalities were identified in a small proportion of patients with mild oesophagits and normal oesophageal peristalsis. Outcome data are needed to evaluate the prognostic value of combined manometry-impedance in patients with GORD undergoing anti-reflux surgery.

Valutazione economica della terapia di mantenimento al bisogno con esomeprazolo nella malattia da reflusso gastroesofageo

Objective Gastro-esophageal reflux disease (GERD) is a common medical problem with a broad spectrum of symptoms and varying degrees of severity and frequency. Most patients with GERD, regardless of endoscopic status, suffer symptomatic relapses within few months from stopping acid suppressant therapy, thus requiring long term management of their disease to prevent relapses. On-demand therapy (i.e., medication taken as needed to relieve symptoms) might be an effective modality of long-term treatment in patients with non-erosive gastro-esophageal reflux disease. An economic evaluation, the ONE (ON-demand treatment with Esomeprazole) study, was conducted to assess costs and consequences over a 6-month period with the 20 mg esomeprazole on-demand strategy compared to the 20 mg once daily continuous therapy in patients with GERD.

Cost minimization of on-demand maintenance therapy with proton pump inhibitors in nonerosive gastroesophageal reflux disease

On-demand proton pump inhibitor maintenance therapy is one of the suggested strategies for patients with nonerosive gastroesophageal reflux disease who achieve symptom remission after 4 weeks of continuous treatment. This review evaluates the difference in cost and quality of life of six on-demand proton pump inhibitor maintenance strategies in patients with nonerosive gastroesophageal reflux disease. This was performed by decision analysis and Markov modeling of costs (from the perspective of the healthcare service and society) and utility up to 12 months. Median utility scores associated with each proton pump inhibitor ranged from 0.731 to 0.745 quality-adjusted life years and were not statistically different. Annual expected cost, however, was statistically different among the different drugs and the following cost-minimization ranking was obtained for median costs to the healthcare service and society, respectively: rabeprazole (€181, €295), pantoprazole (€223, €341), lansoprazole (€249, €370), omeprazole 10 mg (€297, €412), esomeprazole (€295, €419) and omeprazole 20 mg (€405, €528). Unit cost of proton pump inhibitors was the major determinant of cost to the healthcare service, while the number of productivity days lost due to symptoms was the major determinant of cost to society. In Italy, on-demand use of rabeprazole for maintenance therapy of nonerosive gastroesophageal reflux disease incurs the least cost in comparison with the other proton pump inhibitors evaluated.

Enfermedad por reflujo gastroesofágico refractaria a esomeprazol

Resistance to proton pump inhibitors (PPI) in gastroesophageal reflux disease (GERD), which has been described in patients treated with omeprazole, could explain some exceptional cases of treatment failure and the need for surgery. The objective test of resistance to PPI is obtained with 24-hour intragastric pH-metry performed during treatment. A gastric pH of less than 4 for more than 50% of recording time indicates resistance. We present a patient with non-erosive GERD and treatment failure to omeprazole and proven resistance to esomeprazole which, to our knowledge, has only been reported in patients with Barrett's esophagus.

Rabeprazolevsesomeprazole in non-erosive gastro-esophageal reflux disease: A randomized, double-blind study in urban Asia

Gastro-esophageal reflux disease (GERD) is becoming increasingly common in Asia. Data on the efficacy of proton pump inhibitors in patients with non-erosive GERD (NERD) in Asia is lacking. This double-blind study compared the efficacy and safety of rabeprazole with esomeprazole in relief of symptoms in patients with NERD. One hundred and thirty-four patients with reflux symptoms of NERD and normal endoscopy were randomized to receive rabeprazole 10 mg or esomeprazole 20 mg once daily for 4 wk. Symptoms were recorded in a diary and changes in severity of symptoms noted. At 4 wk of treatment, rabeprazole 10 mg and esomeprazole 20 mg were comparable with regards to the primary endpoint of time to achieve 24-h symptom-free interval for heartburn 8.5 d vs 9 d and regurgitation 6 d vs 7.5 d. Rabeprazole and esomeprazole were also similarly efficacious in term of patient's global evaluation with 96% of patients on rabeprazole and 87.9% of patients on esomeprazole, reporting that symptoms improved (P = NS). Satisfactory relief of day- and night-time symptoms was achieved in 98% of patients receiving rabeprazole and 81.4% of patients receiving esomeprazole. Adverse events were comparable in both groups (P = NS). Rabeprazole 10 mg has a similar efficacy and safety profile in Asians with NERD as esomeprazole 20 mg. Further study is necessary to investigate whether the small differences between the two drugs seen in this study are related to the improved pharmacodynamic properties of rabeprazole. Both drugs were well tolerated.

Clinical Response (Remission of Symptoms) in Erosive and Non-Erosive Gastro-Oesophageal Reflux Disease

Complete remission of symptoms and prevention of symptomatic recurrence are among the main therapeutic aims in gastro-oesophageal reflux disease (GORD). In this context, a potent pharmacologic inhibition of gastric acid secretion plays a central role. The goal of antisecretory treatment in GORD is to maintain an intragastric pH greater than 4.0 for the longest possible time. This is best achieved by the administration of proton pump inhibitors (PPIs). Tolerability and safety of different PPIs are similar and consistently high, but therapeutic efficacy may differ among them. Esomeprazole appears to achieve an intragastric pH greater than 4.0 for a larger number of hours compared with any other PPI. This is associated with a greater therapeutic efficacy of esomeprazole compared with omeprazole, lansoprazole and pantoprazole in both complete remission of symptoms and prevention of symptomatic recurrence in GORD. This review provides evidence-based recommendations for the treatment of GORD-related symptoms in clinical practice.

Esophageal Visceral Sensitivity to Bile Salts in Patients with Functional Heartburn and in Healthy Control Subjects

Patients with nonerosive gastroesophageal reflux disease often have relatively low esophageal acid exposure and respond suboptimally to gastric acid suppression. In these patients, other constituents of gastric contents may induce esophageal symptoms. We have demonstrated that gastric contents can cause heartburn when the gastric pH >4. (Aliment Pharm Ther 14:129-134, 2000). The aim of this study was to determine relative sensitivities to chenodeoxycholic and ursodeoxycholic acids, and 0.1 N HCl, administered as provocative perfusion tests. Patients with functional heartburn and healthy control subjects were evaluated. Patients underwent a modified Bernstein acid infusion test and esophageal Barostat balloon distention. Time and volume to pain were recorded. Barostat balloon distention was performed using our standard protocol. Stepwise distentions were performed and pain was recorded. Sensitivity to chenodeoxycholic acid (Cheno) and Ursodeoxycholic acid (Urso) were assessed similarly to the Bernstein test using 2 mM concentrations of each, followed immediately by 5 mM if no pain was reported with 2 mM. Volume of bile acid infusion and length of time until pain was induced were assessed and compared to the same endpoints for acid sensitivity. "Total" time and "total" volume to induce pain were calculated for Cheno and Urso. Least-squares means were generated and two-tailed t-tests and regression analyses were performed (P < 0.05 level of significance). Ten functional heartburn patients and six healthy controls were evaluated (3 M, 13 F; age range, 19 to 56 years). Since five of six controls had pain with acid infusion (hypersensitive), all subjects were analyzed as one group. Only three subjects (all controls) had no pain with infusion of 2 mM Cheno and received the follow-up infusion of 5 mM. These same three subjects tolerated the maximum infusion (150 ml and 15 min) of 5 mM Cheno. Nine subjects did not have pain with 2 mM Urso and received the follow-up infusion of 5 mM Urso (five functional heartburn, four controls). Significantly more subjects tolerated the maximum bile acid infusion of 2 mM Urso vs 2 mM Cheno (nine vs three; P < 0.05, Chi-square test). The pain threshold (volume and time) for Urso was significantly higher than that for Cheno and acid (P < 0.05), and the pain threshold for Cheno was significantly higher than that for acid (P < 0.05). Conclusions are as follows: (1) Bile acids differ in their ability to induce pain. (2) Changing bile acid composition by treatment with Urso may change symptom presentation and symptom severity in patients with bile acid-induced esophageal pain.

Diagnostic Value of Potent Acid Inhibition in Gastro-Oesophageal Reflux Disease

Gastro-oesophageal reflux disease (GORD) is defined as 'Chronic symptoms or mucosal damage produced by abnormal reflux of gastric contents into the esophagus'. The Genval Workshop Report defines that GORD exists when the frequency of heartburn is equal to or greater than 2 days/week and that it is one of the most common gastrointestinal conditions in the general population. Endoscopy is the most recommendable exploratory procedure in a patient with symptoms of GORD, fundamentally heartburn and regurgitation. However, 50-75% of the patients with symptoms compatible with GORD have normal endoscopy. Thus, endoscopy does not appear to be indispensable in a large group of patients with GORD. Endoscopy is therefore the gold standard for the diagnosis of reflux oesophagitis (histopathological changes in the oesophageal mucosa), but there is no gold standard for the diagnosis of non-erosive GORD. Twenty-four-hour pH monitoring has come to be considered the most sensitive and specific test in the diagnosis of GORD, but a significant proportion of patients (about 25%) have symptoms compatible with GORD and have 24-h pH monitoring results that can be considered normal. Besides, demonstrating the presence of acid reflux alone does not prove that it is the cause of suspected GORD-related signs or symptoms. Therefore, despite 'positive' pH studies, there is a significant number of patients failing to respond to therapy, mainly ear, nose and throat complaints, supposed as manifestations of gastro-oesophageal reflux disease. Despite 24-h oesophageal pH testing being an excellent diagnostic tool, it has no utility in routine clinical settings and hence its availability should be limited to tertiary care settings. With the demonstration that antisecretory treatment with high doses of proton pump inhibitors (PPIs) for 1 week or 2 weeks achieves significant improvement or even remission of the symptoms of GORD, it not surprising that it has been proposed as a diagnostic test for the disease. For patients with symptoms compatible with GORD without alarm symptoms or other suspected complications of GORD, a short course of empiric PPI therapy gives valuable information about the presence of GORD. The PPI test is a simple, sensitive and cost-effective tool, but it has insufficient specificity for use as an objective criterion alone. The use of PPIs both as a diagnostic test (1-2 weeks) and as a diagnostic-therapeutic test (1-4 months) has a moderate usefulness and may be used especially in those environments in which there are difficulties in performing the objective test.