Control of Nocturnal Gastric Acidity: A Role for Low Dose Bedtime Ranitidine to Supplement Daily Omeprazole

In some patients, proton pump inhibitors do not abolish nocturnal gastric acidity and additional evening antisecretory medication may be required. In 16 subjects with chronic heartburn, 24-hr gastric and esophageal pH were measured at baseline and again after six days of 20 mg omeprazole alone at 08:00 hr followed by placebo, 75 mg ranitidine, or 20 mg omeprazole at 22:00 hr. Integrated acidity was calculated from the cumulative, time-weighted mean acid concentrations (derived from pH values for each second). Baseline integrated gastric acidity increased progressively over 24 hr, whereas integrated esophageal acidity increased only until 22:00 hr. Morning omeprazole nearly abolished 24-hr esophageal acidity and significantly decreased overall gastric acidity but did not abolish nocturnal gastric acidity. Adding evening ranitidine or omeprazole nearly eliminated the nocturnal increase in gastric acidity. Integrated acidity was more sensitive than time pH < 4 in assessing gastric and esophageal acidity as well as their inhibition by omeprazole and ranitidine. In conclusion, integrated acidity provides novel information regarding the synergy of omeprazole plus ranitidine. Adding low-dose ranitidine helps control nocturnal gastric acidity that can occur with conventional omeprazole administration. Although the heartburn patients in the present study had nocturnal gastric acidity without accompanying nocturnal esophageal acid reflux, other patients who do have nocturnal esophageal reflux might profit from addition of bedtime ranitidine or another gastric antisecretory agent.     

Effect of omeprazole and high doses of ranitidine on gastric acidity and gastroesophageal reflux in patients with moderate-severe esophagitis

Thirty to fifty percent of patients with reflux esophagitis fail to heal after treatment with conventional doses of H2-receptor antagonists, whereas omeprazole administration induces more than 90% healing. To investigate the effect of omeprazole and higher-than-presently-recommended doses of H2-blockers, we evaluated gastric acidity and gastroesophageal reflux in 17 patients with severe-moderate esophagitis before and after treatment with 300 mg ranitidine twice daily or 20 mg omeprazole once daily. Three pH-metric studies were performed, in a cross-over design, before and after 8 days of treatment with omeprazole or ranitidine. Both drugs significantly reduced intragastric acidity (p less than 0.001) during both night and day hours. Median hourly 24-h intragastric pH was 1.8 in the basal study, 2.9 after ranitidine, and 3.4 after omeprazole. Intragastric acidity fell from 84.0 mmol/L in the basal study to 14.2 mmol/L (79% inhibition) with ranitidine and 9.3 mmol/L (84% inhibition) with omeprazole. Patients with esophagitis were significantly more exposed to acid than healthy subjects, in both the supine and upright position (p less than 0.01). The time with esophageal pH less than 4 dropped from 23.9% in the basal study to 8.5% with ranitidine and to 7.2% with omeprazole (p less than 0.001). Both drugs significantly reduced esophageal exposure to acid in both the supine and upright positions (p less than 0.001), whereas neither had any effect on esophageal acid clearance.     

The effect of omeprazole or ranitidine treatment on 24-hour esophageal acidity in patients with reflux esophagitis

Twenty-two consecutive patients with gastroesophageal reflux and erosive or ulcerative esophagitis entered a double-blind, randomized study comparing the effect of 20 mg omeprazole once daily with that of 150 mg ranitidine twice daily on esophageal acidity. Ambulatory 24-h esophageal pH measurements were performed within 1 month before inclusion and after 3 weeks of medication. Omeprazole significantly (p less than 0.05) reduced the number of reflux (pH less than 4) episodes, the number of refluxes lasting greater than 5 min, and the total reflux time. In contrast, ranitidine significantly reduced only the total reflux time. When the two treatment groups were compared, a significant difference in favor of omeprazole was found for daytime and total reflux values, except for the longest reflux and the number of reflux episodes lasting greater than 5 min. Substantial differences, also in favor of omeprazole, were found with regard to the effect on endoscopic healing of the esophagitis.     

Increased acid and bile reflux in Barrett's esophagus compared to reflux esophagitis, and effect of proton pump inhibitor therapy

OBJECTIVES: Barrett's metaplasia is an acquired condition resulting from longstanding gastroesophageal reflux disease. Approximately 10% of esophagitis patients develop Barrett's esophagus. There is increasing evidence that duodenogastroesophageal reflux plays a role in the progression of disease. We further analyzed the correlation of acid and biliary reflux with reflux esophagitis and Barrett's esophagus and tested the effects of proton pump inhibitor therapy. METHODS: Patients with either reflux esophagitis (group 1) or Barrett's esophagus (group 2) prospectively underwent simultaneous 24-h esophageal pH and bile reflux testing without any therapy affecting acid secretion or GI motility. A total of 16 patients in group 1 and 18 patients in group 2 were tested again under proton pump inhibitor therapy. RESULTS: Acid and bile exposure were significantly increased in Barrett's patients (n = 23) compared to 20 esophagitis patients (median percentage of time that pH was <4 was 24.6% vs 12.4%, p = 0.01, median percentage of time that bilirubin absorbance was >0.2 was 34.7% vs 12.8%, p < 0.05). During therapy, both acid and bile reflux decreased significantly in both groups. Median percentage of time that pH was <4 and bilirubin absorbance was >0.2 before and during therapy was 18.2%/2.3% and 29.8%/0.7% (p = 0.001 and p = 0.001) in Barrett's esophagus patients versus 14.5%/3.6% and 21.5%/0.9% (p = 0.002 and p = 0.011) in esophagitis patients. There was no significant difference between the groups. In two esophagitis patients, bile reflux increased during therapy. CONCLUSIONS: There is a good correlation of the duration of esophageal exposure to acid and bile with the severity of pathological change in the esophagus. Both acid and bile reflux is significantly suppressed by proton pump inhibitor therapy with exceptions among individual esophagitis patients. The prolonged simultaneous attack of bile and acid may play a key role in the development of Barrett's metaplasia.     

Gastric and esophageal acidity during continuous treatment with H2-antagonists in uncomplicated esophagitis

Twenty-four-hour gastric and esophageal pH were monitored simultaneously in 19 patients with moderate esophagitis before and after a randomized crossover treatment with 40 mg famotidine or 300 mg ranitidine. Gastroesophageal reflux in patients with esophagitis was compared with that in 22 healthy controls. Patients with esophagitis had more esophageal acidity than controls; the percentage of time with esophageal pH less than 4 was significantly greater during a 24-h period (p less than 0.01) both in the upright (p less than 0.01) and in the supine (p less than 0.01) position. In esophagitis patients the percentage of time with pH less than 4 during the total 24-h period correlated closely with acid reflux in the upright (p less than 0.001) and supine (p less than 0.01) position. This indicates that daytime reflux is probably as injurious to the esophagus as nighttime reflux. Famotidine and ranitidine decreased gastric acidity during the entire 24-h period (p less than 0.001) but not during the daytime or early evening. The inhibitory effect lasted slightly longer with famotidine (12 h) than with ranitidine (10 h). Famotidine and ranitidine reduced esophageal acidity during the entire 24-h period (p less than 0.001) and particularly during the nighttime (p less than 0.001) but not during the daytime. Famotidine and ranitidine also did not modify the esophageal acid clearance. Nightly doses of famotidine or ranitidine were ineffective in reducing GER during daytime hours.     

Nocturnal acid breakthrough: clinical significance and correlation with esophageal acid exposure

OBJECTIVES: Previous studies suggest that the addition of H2 receptor antagonist (H2RA) therapy is more effective than proton pump inhibitor (PPI) therapy alone in reducing nocturnal acid breakthrough (NAB). However, the clinical significance of NAB with respect to esophageal acid control has not been investigated. The aim of this study was to evaluate prospectively the degree of upright and supine esophageal and gastric acid suppression using various PPI regimens in comparison to the addition of an H2RA at bedtime. METHODS: A total of 22 subjects (13 with gastroesophageal reflux disease and nine who served as control subjects) were prospectively evaluated by serial combined esophageal and gastric 24-h pH monitoring. Studies were performed at baseline off antireflux medical therapy and subsequent to completion of the following four drug regimens: 1) omeprazole 20 mg b.i.d. for 2 wk; 2) omeprazole 20 mg b.i.d. plus ranitidine 300 mg HS for 4 wk; 3) omeprazole 20 mg QAM and QHS for 2 wk; and 4) omeprazole 20 mg every 8 h for 2 wk. A dual pH probe was placed 5 cm above and 10 cm below the manometrically defined LES for a minimum of 18 h. Median total, upright, and supine pH values were compared among treatment regimens. All subjects underwent Helicobacter pylori serology testing. RESULTS: A total of 17 men and eight women (mean age 37 yr +/- 2.4 yr, range 22-71 yr) were enrolled in the study. Total, upright, and supine median percentage of the time that gastric pH was <4 were significantly less than baseline values in all treatment regimens. Although patients treated with Q8 h omeprazole had significantly (p < 0.01) more gastric acid suppression, there was a high degree of overlap among regimens. Treatment regimens resulted in NAB elimination of 9-41%. However, no single treatment regimen resulted in more significant NAB suppression than the others. Despite continued NAB with all treatment regimens, esophageal acid reflux (90%) and patient symptoms (100%) were well controlled. In addition, there were no differences in the esophageal median percentage of time that pH was <4 for any treatment regimen. CONCLUSIONS: NAB is an isolated gastric phenomenon that is poorly controlled even with most aggressive acid suppressive therapy. Esophageal acid suppression and symptom control are not dependent on the degree of NAB elimination.     

Letter to the Editor: Triticum moncoccum and celiac disease

Twenty-two consecutive patients with gastroesophageal reflux and erosive or ulcerative esophagitis entered a double-blind, randomized study comparing the effect of 20 mg omeprazole once daily with that of 150 mg ranitidine twice daily on esophageal acidity. Ambulatory 24-h esophageal pH measurements were performed within 1 month before inclusion and after 3 weeks of medication. Omeprazole significantly (p < 0.05) reduced the number of reflux (pH < 4) episodes, the number of refluxes lasting >5 min, and the total reflux time. In contrast, ranitidine significantly reduced only the total reflux time. When the two treatment groups were compared, a significant difference in favor of omeprazole was found for daytime and total reflux values, except for the longest reflux and the number of reflux episodes lasting >5 min. Substantial differences, also in favor of omeprazole, were found with regard to the effect on endoscopic healing of the esophagitis.     

Effect of Omeprazole on Gastroesophageal Reflux in Barrett''s Esophagus

Pattern of gastric and esophageal acidity were evaluated in 14 patients with endoscopically and histologically proven Barrett's esophagus, in 46 with slight-to-moderate esophagitis, and in 22 healthy subjects. In patients with Barrett's esophagus, LES pressure was considerably lower and percentage exposure to acid was considerably higher than in either patients with esophagitis or controls (p less than 0.001). Percentage of time with esophageal pH below 4 was 33.2% in patients with Barrett's esophagus, 14% in patients with slight-to-moderate esophagitis (p less than 0.001), and 3.4% in controls (p less than 0.001). In patients with Barrett's esophagus, the esophageal exposure to acid was similar in upright and supine positions, and the number of refluxes that lasted longer than 5 min was also greater in these patients than in uncomplicated esophagitis or controls (p less than 0.001). Accordingly, their acid-clearing capacity was markedly reduced (p less than 0.001 vs. control). Omeprazole 20 mg, given once daily, reduced both percentage of time with pH below 4 (p less than 0.001) and the number of episodes longer than 5 min (p less than 0.001), but had no effect on acid clearance. In patients with Barrett's esophagus, omeprazole lowered intragastric acidity by 77.8% (p less than 0.001). Median intragastric pH was 1.9 (1.7-2.1) pretreatment, and 4.5 (4.2-5) during omeprazole (p less than 0.001).     

Nocturnal recovery of gastric acid secretion with twice-daily dosing of proton pump inhibitors

Objective: It is our experience that many patients treated with proton pump inhibitors (PPI) b.i.d . recover acid secretion during the night. Our aim was to assess the efficacy of omeprazole and lansoprazole b.i.d . on nocturnal gastric acidity.
Methods: Three groups were studied with intragastric pH monitoring. Group 1 consisted of 17 patients with gastroesophageal reflux disease (GERD) taking omeprazole 20 mg b.i.d . Group 2 was 16 male volunteers taking omeprazole 20 mg b.i.d . and Group 3 comprised 12 volunteers taking lansoprazole 30 mg b.i.d. .
Results: The percentages of time that subjects had pH < 4 were lower during supine than upright periods in Groups 1 and 3 (   P < 0.01  ). Recovery of nocturnal acid secretion lasting > 1 h, termed acid breakthrough, occurred in three-fourths of all individuals within 12 h from intake of the evening dose of PPI. Median time to acid breakthrough for the whole group was 7.5 h.
Conclusions: Nocturnal acid breakthrough occurs in a majority of patients and normal volunteers taking PPI b.i.d.     

Determinants of Long-Term Outcome of Patients with Reflux-Related Ear, Nose, and Throat Symptoms

Gastroesophageal reflux disease (GERD) is present in up to 75% of patients with chronic refractory ear, nose, and throat (ENT) symptoms, and proton pump inhibitor (PPI) therapy induces symptom relief in the majority of these patients. It has been suggested that endoscopic findings and quantification of esophageal acid exposure may help to predict the long-term outcome of medical therapy, but prospective studies that confirm this hypothesis are lacking. The aim of the present study was to investigate the relationship of endoscopic findings and quantification of reflux with long-term outcome in patients with reflux-related ENT symptoms. One hundred six consecutive patients with chronic refractory unexplained ENT symptoms underwent upper GI endoscopy, 24-hr dual-channel esophageal pH and Bilitec (n = 35) monitoring, and esophageal manometry. Subsequently, all were treated with omeprazole, 20 mg b.i.d., and patients were followed at 2-week intervals until symptom relief. Four weeks later, omeprazole therapy was gradually decreased and the lowest effective omeprazole maintenance dose, if any, was determined. Eighty-one patients (49 men; mean age, 50) experienced a clear or excellent therapeutic response after, on average, 4 weeks of omeprazole, 20 mg b.i.d. In 36 patients (44%; group A), PPI treatment could be stopped completely, 27 patients (33%; group B) required a maintenance dose of omeprazole, 20 mg/day, and 18 patients (22%; group C) required maintenance with omeprazole, 40 mg/day. The prevalence of reflux esophagitis was significantly lower in group A patients, who also had significantly lower distal esophageal acid exposure, proximal esophageal acid exposure, and esophageal duodenogastroesophageal reflux exposure compared to groups B and C. Multivariate analysis identified the presence of esophagitis and pathological distal esophageal acid exposure as risk factors for the need of maintenance therapy. In patients with reflux-related ENT symptoms, initial findings on upper GI endoscopy and 24-hr pH-metry help to predict the need for maintenance therapy.     

The effect of rabeprazole alone or in combination with H2 receptor blocker on intragastric pH: a pilot study.

BACKGROUND/AIMS: Proton pump inhibitors have been widely used in recent years. However, there are studies suggesting that proton pump inhibitors may not control the gastric acidity effectively during the night, especially in gastroesophageal reflux disease. It has therefore been suggested that H2 receptor blockers should be added to the therapy. The aim of our study was to evaluate the effects of proton pump inhibitors alone or in combination with H2 receptor blockers on gastric acidity with 24-hour gastric pH monitoring. METHODS: Esophagogastroscopy and 24-hour gastric pH monitoring were performed on 10 patients with dyspeptic symptoms. No patient had antacidity. All patients had erosive antral gastritis. Patients were randomized to two groups as either proton pump inhibitor therapy group (rabeprazole 20 mg/day, p.o.) or proton pump inhibitor + H2 receptor blocker therapy group (rabeprazole 20 mg/day, p.o. + famotidine 40 mg/day, p.o). After one month of treatment, 24-hour gastric pH monitoring was re-performed. RESULTS: Seven female and three male patients were enrolled into the study. The mean age was 51.1+/-11.56 years. All patients had antral erosive gastritis. Gastric pH was measured as less than 4 in 81.4% of the 24-hour period prior to rabeprazole treatment. With rabeprazole treatment this ratio decreased to 27.6% (p<0.05). These ratios were 86.3% and 4.55%, respectively, in the group that received combination therapy (p<0.05). CONCLUSIONS: Combination therapy with H2 receptor blockers and proton pump inhibitors seemed to control intra-gastric pH better than proton pump inhibitors alone. Use of H2 receptor blockers and proton pump inhibitors in combination to control intra-gastric pH is more beneficial.     

Symptom relief in patients with reflux esophagitis: comparative study of omeprazole, lansoprazole, and rabeprazole

BACKGROUND AND AIM: Rabeprazole has a faster onset of antisecretory activity than omeprazole and lansoprazole. The aim of the present study was to clarify whether there is any difference in the speed of symptom relief in patients with reflux esophagitis following the administration of these three proton pump inhibitors (PPI). METHODS: Eighty-five patients with erosive reflux esophagitis were randomized to receive 8 weeks of 20 mg of omeprazole (n = 30), 30 mg of lansoprazole (n = 25), or 20 mg of rabeprazole (n = 30) once a morning. Daily changes in heartburn and acid reflux symptoms in the first 7 days of administration were assessed using a six-point scale (0: none, 1: mild, 2: mild-moderate, 3: moderate, 4: moderate-severe, 5: severe). RESULTS: The mean heartburn score in patients administered rabeprazole decreased more rapidly than those given the other PPI. Complete heartburn remission also occurred more rapidly in patients administered rabeprazole (compared with omeprazole: P = 0.035, compared with lansoprazole: P = 0.038 by log-rank test). No differences were seen in the rate of endoscopic healing of reflux esophagitis at 8 weeks between the three treatment regimens. CONCLUSION: Rabeprazole may be more effective than omeprazole and lansoprazole for the rapid relief of heartburn symptoms in patients with reflux esophagitis.     

Gastric acidity and gastroesophageal reflux patterns in patients with esophagitis.

Esophageal pH-metry is the test of choice for diagnosing gastroesophageal reflux. However, although it allows acid refluxes to be distinguished, it is of limited value for identifying alkaline or mixed (acid mixed with alkaline material) refluxes. To evaluate the ability of dual pH-metry to identify alkaline or mixed refluxes, the gastric acidity and gastroesophageal reflux pattern were evaluated simultaneously in 64 patients with mild-moderate esophagitis, in 28 patients with severe or complicated esophagitis, and in 20 healthy subjects. A dual esophageal gastric pH-probe allowed three different types of esophageal reflux to be distinguished: (a) acid refluxes, defined as a drop in esophageal pH to values less than 4 together with a gastric pH less than 4; (b) mixed refluxes, defined as a drop in esophageal pH from baseline to values greater than 4 associated with rises in gastric pH to greater than 4 values; (c) alkaline refluxes, defined as a rise in esophageal pH to greater than 7 associated with a simultaneous increase in gastric pH to greater than 4. Gastric acidity was more significantly reduced in patients with severe or complicated esophagitis than it was in healthy subjects (P less than 0.01). The reflux pattern in both mild-moderate and severe esophagitis was characterized by mainly acid refluxes and a marked increase in the time the esophagus mucosa was exposed to acid (P less than 0.001). Pure alkaline refluxes were rare (less than 1%) in both healthy subjects and esophagitis patients. The number of mixed refluxes was considerably higher in severe esophagitis patients than it was in either mild-moderate esophagitis patients or controls (P less than 0.05). The finding of mixed refluxes in severe or complicated esophagitis suggests that biliary acids and/or pancreatic enzymes are involved in the pathogenesis of severe forms of esophagitis.     

奥美拉唑治疗前后糜烂性食管炎患者食管鳞状上皮细胞间隙的变化

目的观察糜烂性食管炎患者应用奥美拉唑治疗前后食管鳞状上皮细胞间隙的改变。方法20例经胃镜确诊的糜烂性食管炎患者给予奥美拉唑20mg,2次／d,治疗4周后复查胃镜。治疗前后2次胃镜检查时于齿状线上方2cm取活检,观察透射电镜下鳞状上皮细胞间隙的变化。治疗前后患者分别接受症状问卷,症状严重程度用积分表示。结果治疗前平均细胞间隙、最大细胞间隙和最小细胞间隙分别为（1．14±0．15）μm、（1．47±0．15）μm、（0．85±0．17）μm;治疗后分别为（O．51±0．18）μm、（0．72±0．25）μm、（0．36±0．15）μm,与治疗前比较差异有统计学意义（P=0．000）。结论短期应用奥美拉唑治疗可以使糜烂性食管炎患者增宽的食管下段鳞状上皮细胞间隙恢复至正常。     

Selection of patients for successful maintenance treatment of esophagitis with low-dose omeprazole: use of 24-hour gastric pH monitoring

OBJECTIVE: Treating patients with erosive esophagitis and maintaining remission in a cost-effective fashion is a desirable goal in clinical practice. There are no established criteria to identify patients with healed esophagitis who will subsequently remain in remission with low-dose omeprazole therapy. We investigated whether 24-h esophageal-gastric pH monitoring could provide criteria to select patients for low-dose omeprazole maintenance therapy. METHODS: Seventy consecutive symptomatic outpatients with grade 2-3 reflux esophagitis were prospectively investigated. They were treated with 20 mg/day omeprazole for 2 months. Those with healed esophagitis were given alternate-evening 20-mg omeprazole maintenance therapy for 6 months. Clinical evaluation, endoscopy, and 24-h esophageal-gastric pH were done at the end of each treatment period. Results of pH studies of patients in remission were compared with those with endoscopically documented relapse of esophagitis. RESULTS: In 63/70 patient (intention-to-treat, 90%; 95% confidence interval [CI], 83-97%) esophagitis was healed at 2 months. During the 6-month maintenance period esophagitis remain healed in 28 (G1) (40%; 95% CI, 29-52%), but recurred in 32 patients (G2). During healing with omeprazole 20 mg/day the 24-h gastric pH was below 4 for <10% of the time in 96% of the patients, who subsequently remained in long-term remission with low-dose maintenance therapy (G1), but not in any patient with recurrence of esophagitis (G2). The 10% threshold value has a specificity of 1.00 and sensitivity of 0.96. CONCLUSIONS: The 24-h intragastric pH monitoring during 20 mg/day omeprazole therapy provides criteria by which to preselect patients with reflux esophagitis who will remain in remission with low-dose omeprazole therapy.     

Assessment of effectiveness of different dosage regimens of pantoprazole in controlling symptoms and healing esophageal lesions of patients with mild erosive esophagitis

BACKGROUND: Gastroesophageal reflux disease is a very common affection, and esophageal involvement is particularly frequent. The means to effectively control symptoms and improve esophageal inflammation in these patients is to reduce esophageal acid exposure. For this purpose, we use gastric proton pump inhibitor, that can suppress gastric acid secretion. AIM: To compare the effectiveness of two different pantoprazole dosage regimens (20 and 40 mg/day), in controlling symptoms and healing esophageal lesions of patients with mild erosive esophagitis. MATERIAL AND METHODS: Fifty-seven patients with endoscopically confirmed mild erosive esophagitis characterized as non-confluent erosions in the distal esophagus, were randomly to be treated either with pantoprazole 20 mg/day (group I, 28 patients) or 40 mg/day (group II, 29 patients) over a period of 4 weeks. After treatment completion, the patients were assessed for clinical and endoscopic outcome, i.e., absence of erosions in distal esophagus and improvement of gastroesophageal reflux symptoms. RESULTS: At the end of the treatment, 73.1% of the patients in group I and 85.7% of the patients in group II had endoscopic improvement. We also observed, that 88.5% of the patients in group I and 92.9% of the patients in group II had complete elimination of heartburn and regurgitation. CONCLUSION: Pantoprazole dosage regimens of 20 mg/day and 40 mg/day provide equivalent effectiveness in controlling symptoms and healing esophageal lesions of mild esophagitis.     

Integrated acidity and the pathophysiology of gastroesophageal reflux disease

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

Long-term omeprazole and esomeprazole treatment does not significantly increase gastric epithelial cell proliferation and epithelial growth factor receptor expression and has no effect on apoptosis and p53 expression

AIM: To study the effect of proton pump inhibitor (PPI) treatment on patients with reflux esophagitis and its in vivo effect on apoptosis, p53- and epidermal growth factor receptor (EGFR) expression. METHODS: After informed consent was obtained, gastric biopsies of the antrum were taken from patients with reflux oesophagitis prior to and after 6 mo of 20 mg omeprazole (n = 14) or 40 mg esomeprazole (n=12) therapy. Patients did not take any other medications known to affect the gastric mucosa. All patients were Helicobacter pylori negative as confirmed by rapid urease test and histology, respectively. Cell proliferation, apoptosis, EGFR, and p53 expression were measured by immunohistochemical techniques. At least 600 glandular epithelial cells were encountered and results were expressed as percentage of total cells counted. Was considered statistically significant. RESULTS: Although there was a trend towards increase of cell proliferation and EGFR expression both in omeprazole and esomeprazole treated group, the difference was not statistically significant. Neither apoptosis nor p53 expression was affected. CONCLUSION: Long-term PPI treatment does not significantly increase gastric epithelial cell proliferation and EGFR expression and has no effect on apoptosis and p53 expression.     

Predominant nocturnal acid reflux in patients with Los Angeles grade C and D reflux esophagitis

BACKGROUND AND AIMS: Nocturnal gastric acid breakthrough (NAB) is defined as an intragastric pH < 4.0 lasting more than 1 h during the night in patients taking a proton pump inhibitor (PPI). Gastroesophageal reflux disease (GERD) patients with nocturnal gastroesophageal acid reflux accompanied by NAB are thought to be refractory to PPI treatment. The aim of this study was to endoscopically identify the patients with predominant nocturnal gastroesophageal acid reflux. METHODS: The subjects were 37 patients with erosive reflux esophagitis (Los Angeles classification (LA) grade A, 12; B, 10; C, eight; and D, seven cases) and a control group of 20 patients without esophagitis. The results of ambulatory 24 h gastric and esophageal pH monitoring were compared among different grades of esophagitis. RESULTS: Gastroesophageal reflux during 24 h in patients with high-grade esophagitis was more frequent than for patients with low-grade esophagitis or no esophagitis. Although the length of esophageal acid exposure (percentage time with pH < 4.0) in patients with grade A or without esophagitis was longer in the daytime, that in patients with grades C and D was longer during the night. The reason for the delayed nocturnal acid exposure was the longer nocturnal acid clearance in high-grade reflux esophagitis. CONCLUSIONS: Nocturnal exposure of the esophagus to acid occurs frequently in patients with LA grades C and D esophagitis. Thus, the existence of NAB with resulting nocturnal acid reflux should be considered when the patient with high-grade esophagitis shows resistance to PPI treatment.     

Long-term omeprazole and esomeprazole treatment does not significantly increase gastric epithelial cell proliferation and epithelial growth factor receptor expression and has no effect on apoptosis and p53 expression

AIM: To study the effect of proton pump inhibitor (PPI)treatment on patients with reflux esophagitis and its in vivo effect on apoptosis, p53- and epidermal growth factor receptor (EGFR) expression.METHODS: After informed consent was obtained, gastric biopsies of the antrum were taken from patients with reflux oesophagitis prior to and after 6 mo of 20 mg omeprazole (n = 14) or 40 mg esomeprazole (n = 12) therapy.Patients did not take any other medications known to affect the gastric mucosa. All patients were Helicobacter pylori negative as confirmed by rapid urease test and histology,respectively. Cell proliferation, apoptosis, EGFR, and p53expression were measured by immunohistochemical techniques. At least 600 glandular epithelial cells were encountered and results were expressed as percentage of total cells counted. Was considered statistically significant.RESULTS: Although there was a trend towards increase of cell proliferation and EGFR expression both in omeprazole and esomeprazole treated group, the difference was not statistically significant. Neither apoptosis nor p53 expression was affected.CONCLUSION: Long-term PPI treatment does not significantly increase gastric epithelial cell proliferation and EGFR expression and has no effect on apoptosis and p53 expression.