Absence of nocturnal acid breakthrough in Helicobacter pylori-positive subjects treated with twice-daily omeprazole

BACKGROUND: Proton pump inhibitors (PPIs) taken twice daily do not effectively control night-time intragastric pH; nocturnal acid breakthrough (NAB) (arbitrarily defined as intragastric pH < 4 lasting longer than 1 h) occurs in more than 75% of patients. The effectiveness of PPIs depends rather on the Helicobacter pylori status. OBJECTIVES: To investigate the effectiveness of two regimens of omeprazole in H. pylori-positive subjects as well as the occurrence of NAB. PATIENTS: Fifteen otherwise healthy H. pylori-positive subjects participated in this randomized, crossover, double-blind study. METHODS: Night-time intragastric pH-metry was performed before (baseline) and on day 7 of two treatment courses with omeprazole (1 x 20 mg and 2 x 20 mg). A 14-day (minimum) wash-out period was respected between the two treatment courses. RESULTS: Group medians (10-90% confidence intervals) for night-time intragastric pH (22:30-06:30 h) were as follows: baseline, 2 (1-6.1); 1 x 20 mg, 5 (3.3-6.9; P < 0.001 versus baseline); instead of, 2 x 20 mg, 6.3 (4.9-7.1; P < 0.001 versus baseline, P = 0.02 versus omeprazole 1 x 20 mg). The percentage of time with intragastric pH < 3 was 65.4% during baseline (P < 0.05 versus both omeprazole regimens), 27% with once-daily omeprazole (P = 0.001 versus omeprazole 2 x 20 mg) and 0% with twice-daily omeprazole. NAB occurred in eight (53.3%) subjects with once-daily omeprazole and in no subject taking twice-daily omeprazole. CONCLUSIONS: In H. pylori-positive subjects, twice-daily omeprazole is highly effective in controlling nocturnal intragastric acidity. NAB does not occur in those subjects and there is no need to add bedtime H2-receptor antagonists to this regimen.     

Long-term effect of H2RA therapy on nocturnal gastric acid breakthrough

BACKGROUND & AIMS: Adding histamine 2 receptor antagonists (H2RAs) to proton pump inhibitor (PPI) therapy is a common practice to block nocturnal acid breakthrough (NAB). Controversy exists over its efficacy because of H2RA intolerance. No prospective study has addressed this issue. METHODS: Twenty-three healthy volunteers and 20 gastroesophageal reflux disease (GERD) patients were studied. Ambulatory pH monitoring was performed with one electrode in the gastric fundus and the other 5 cm above the lower esophageal sphincter. Baseline pH testing was performed and repeated after 2 weeks on PPI twice daily before meals (omeprazole 20 mg). All subjects then received 28 days of PPI plus H2RA Qhs (ranitidine 300 mg) with repeat pH testing on days 1, 7, and 28. RESULTS: Eighteen controls and 16 GERD patients completed all 5 studies. Compared with baseline, all 4 medication regimens decreased supine % time pH < 4 (P = 0.001). The administration of PPI + 1 day of H2RA was the only therapy that significantly decreased % time gastric pH < 4 for the supine period compared with PPI twice daily alone (P < 0.001). There was no difference in % time supine gastric pH < 4 between 2 weeks of PPI twice daily alone and either 1 week or 1 month of PPI + bedtime H2RA. CONCLUSIONS: The combination of H2RA and PPI therapy reduced NAB only with the introduction of therapy. Because of H2RA tolerance, there is no difference in acid suppression between PPI twice daily and PPI twice daily + H2RA after 1 week of combination therapy.     

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.     

Gastric Acid Normosecretion Is Not Essential in the Pathogenesis of Mild Erosive Gastroesophageal Reflux Disease in Relation to Helicobacter pylori Status

In the pathogenesis of gastroesophageal reflux disease (GERD), gastric acid is considered to be one of the most important factors, but little is known about the degree of gastric acid secretion in GERD patients. In this study, we evaluated it in GERD patients and control subjects by 24-h intragastric pH, and serological and histological investigations, in relation to Helicobacter pylori (H. pylori) status. In H. pylori-negative GERD patients gastric acid secretion was similar to that in H. pylori-negative control subjects. In H. pylori-positive GERD patients, in particular, mild GERD patients, it decreased significantly compared to that in H. pylori-negative control subjects, but the degree of decrease was smaller than in H. pylori-positive control subjects. Results of serological and histological evaluation were supportive. In conclusion, in some GERD patients, gastric acid secretion was significantly decreased. Increased or maintained gastric acid secretion was not essential in the pathogenesis of mild GERD.     

Helicobacter pylori infection prevents nocturnal gastric acid breakthrough

BACKGROUND/AIMS: Nocturnal gastric acid breakthrough (NAB) is given attention as one of the factors that cause refractory reflux esophagitis. However, its clinical states and mechanisms are not yet clearly understood. We studied whether there will be a NAB outbreak or not among healthy Japanese male volunteers upon administration of omeprazole, as well as what kind of factors will be involved in case of an outbreak. METHODOLOGY: Twenty-one volunteers were selected as subjects for this research. Subjects were checked for symptoms as well as for esophageal hiatal hernia, atrophic patterns and Helicobacter pylori infection of the gastric mucosa. We also conducted esophageal and gastric 24h pH monitoring twice before and after administration of 20mg omeprazole. We further studied CYP2C19 gene polymorphism. RESULTS: We observed NAB outbreak in 9 cases (42.9%) among 21 subjects. All 6 cases (100%) in the H. pylori-positive group showed NAB negative while 6 (40%) of the 15 cases in the H. pylori-negative group showed NAB negative. We found a statistically significant difference between these two groups (P=0.012). We also found a tendency that NAB outbreak is affected by CYP2C19 gene polymorphism. CONCLUSIONS: H. pylori infection prevents NAB among healthy Japanese male volunteers under administration of omeprazole.     

Intragastric nitric oxide/nitrite in Helicobacter pylori-infected subjects

BACKGROUND: Nitrite (NO2-) in swallowed saliva is reduced to nitric oxide (NO) and other nitrogen oxides by the intragastric acidity. This mechanism is probably important for the intragastric clearance of ingested micro-organisms and nitrosating compounds. The study examines the balance between intragastric NO and NO2- in relation to endogenous acid production and infection with Helicobacter pylori. METHODS: Six healthy H. pylori-negative and six H. pylori-positive volunteers with no known gastroduodenal pathology were examined after an overnight fast. Gastric NO was measured using a chemiluminescence technique and pH as well as NO2- were analysed in gastric aspirates. RESULTS: Gastric NO was slightly lower in H. pylori-positive subjects (1560 +/- 211 ppb) than in uninfected controls (2112 +/- 430 ppb; P > 0.05) during basal conditions, whereas both pH and NO2- concentration were similar in the two groups. During inhibition of acid secretion (omeprazole 20 mg b.i.d. over 5 days) median pH and mean NO2- concentration in gastric aspirates were significantly higher in H. pylori positives than in the controls. Furthermore, during omeprazole treatment the intragastric NO levels were almost absent in H. pylori positives, whereas approximately 50% remained in H. pylori-negative individuals. CONCLUSION: Proton-pump inhibition in H. pylori-infected individuals abolishes the intragastric chemical reduction of swallowed NO2- in the fasting stomach.     

Influence of H pylori on plasma ghrelin in patients without atrophic gastritis

AIM:To determine the association between H pylori infection and serum ghrelin levels in patients without atrophic gastritis.METHODS:Fifty consecutive patients(24 males and 26 females)with either H pylori-positive gastritis(n = 34)or H pylori-negative gastritis(n = 16)with normal gastric acid secretion determined by 24-h pHmetry and without atrophic gastritis in histopathology were enrolled in this study.Thirty-four H pylori-infected patients were treated with triple therapy consisting of a daily regimen of 30 mg lansoprazole bid,1 g amoxicillin bid and 500 mg clarithromycin bid for 14 d,followed by an additional 4 wk of 30 mg lansoprazol treatment.H pylori infection was eradicated in 23 of 34(67.6%)patients.H pylori-positive patients were given eradication therapy.Gastric acidity was determined via intragastric pH catethers.Serum ghrelin was measured by radioimmunoassay(RIA).RESULTS:There was no signifficant difference in plasma ghrelin levels between H pylori-positive and H pylori-negative groups(81.10 ± 162.66 ng/L vs 76.51 ± 122.94 ng/L).In addition,there was no significant difference in plasma ghrelin levels and gastric acidity levels measured before and 3 mo after the eradication therapy.CONCLUSION:H pylori infection does not influence ghrelin secretion in patients with chronic gastritis without atrophic gastritis.     

Clinical usefulness of serum pepsinogen II in the management of Helicobacter pylori infection

BACKGROUND: Serum pepsinogen II (sPGII) levels are known to increase during Helicobacter pylori infection. AIM: To assess H. pylori infection and success of H. pylori therapy by means of sPGII levels. METHODS: sPGII levels were determined in 156 H. pylori-positive and 157 H. pylori-negative consecutive patients with dyspeptic symptoms. Additionally, sPGII determination was performed in 70 H. pylori-positive patients 2 months after H. pylori eradication therapy. In 29 of these 70 patients, gastroscopy was performed to evaluate the effect of H. pylori therapy on gastric activity. RESULTS: H. pylori-positive subjects demonstrated a significantly higher mean of sPGII levels than H. pylori-negative subjects (16.8 +/- 7.4 vs. 8.6 +/- 3.7 microg/l; p < 0.001). The best sPGII cut-off for predicting H. pylori infection was 9.93 microg/l (sensitivity 83%, specificity 73%). The best cut-off values to evaluate success of therapy were: sPGII of 9.47 microg/l, a sPGII variation level (difference between baseline and after therapy) of 4.54 microg/l, and a sPGII Deltavalue (sPGII variation divided by sPGII before therapy) of 25% (sensitivity 93%, specificity 91%). CONCLUSIONS: sPGII levels may be used as a reliable marker of H. pylori infection in the initial diagnosis as well as to evaluate H. pylori eradication and subsequent changes in gastric inflammation.     

Omeprazole, Helicobacter pylori status, and alterations in the intragastric milieu facilitating bacterial N-nitrosation

BACKGROUND & AIMS: Omeprazole produces greater acid inhibition in Helicobacter pylori-positive than -negative subjects. We investigated whether this is accompanied by more profound changes in the intragastric milieu that facilitates bacterial synthesis of N-nitroso compounds. METHODS: Gastric juice pH; nitrite, ascorbic acid, and total vitamin C concentrations; and colonization by other bacteria were examined before and during omeprazole treatment in subjects with and without H. pylori infection. Studies were performed in the fasting state and after consumption of 2 mmol nitrate (equivalent to a salad meal). RESULTS: Before omeprazole, H. pylori-positive and -negative subjects were similar for all parameters. During omeprazole, H. pylori-positive subjects had a higher intragastric pH (7.8 vs. 3.0; P < 0.00001) and greater colonization with non-H. pylori species (5 x 10(7) vs. 5 x 10(5) CFU/mL; P < 0.05). These bacteria included nitrosating species. During omeprazole treatment, H. pylori-positive subjects had higher intragastric nitrite levels after the nitrate meal (median area under the concentration/time curve, 12,450 vs. 4708 micromol/L. min; P = 0.04). Omeprazole lowered intragastric vitamin C levels in H. pylori-positive but not -negative subjects (1.8 vs. 3.4 microg/mL, respectively; P = 0.02). CONCLUSIONS: In H. pylori-positive subjects, omeprazole produces disturbances in intragastric nitrite, vitamin C, and bacterial colonization that facilitate bacterial N-nitrosation. This may place them at increased risk of mutagenesis and carcinogenesis.     

Evolution of gastritis in patients with gastric erosions

OBJECTIVE: Gastric erosions are mainly associated with Helicobacter pylori infection and non-steroidal anti-inflammatory drugs (NSAIDs), but there has been no information available on the long-term evolution of gastritis in subjects with erosions. MATERIAL AND METHODS: A series of 117 patients with gastric erosions without peptic ulcer disease and matched controls without erosions or ulcers were studied. Available subjects underwent endoscopy and biopsy 17 years later. Parietal cell antibodies were analysed at the first visit. RESULTS: Fifty-two patients and 67 controls were available for follow-up. Since H. pylori was a major determinant of gastritis, only subjects with unchanged H. pylori status were included in the evaluation of gastritis progression. At the follow-up visit, gastric erosions were present in 38% (16/42) of the patients and 11% (5/46) of the controls (p=0.005). In H. pylori-negative subjects, no evolution of histological changes was seen. In H. pylori-positive subjects, body gastritis was initially less active in the erosion group. With time, antral gastritis worsened only in the erosion group. Parietal cell antibodies were more common in the control group (23%; erosion patients 0%; p=0.01), which also showed worsening of gastritis (p=0.003) and aggravation of atrophy (p=0.002) in the body mucosa. CONCLUSIONS: Gastritis in H. pylori-positive subjects with gastric erosions shows evolution of antral predominance, body predominance including development of atrophic changes being rare. Accordingly, patients with erosions share the characteristics of gastritis of the duodenal ulcer phenotype. These findings support the importance of H. pylori and acid in the pathogenesis of gastric erosions in H. pylori-positive patients.     

Nocturnal gastric acid breakthrough during the administration of rabeprazole and ranitidine in Helicobacter pylori-negative subjects: effects of different regimens

Background. Nocturnal gastric acid breakthrough (NAB) is defined as nocturnal intragastric pH less than 4 for more than 1h during proton pump inhibitor (PPI) administration. A bedtime dose of an H2 receptor antagonist (H2RA) inhibites NAB, but the efficacy of the H2RA decreases with continuous administration. We carried out the present study to investigate the effect of 14-day H2RA administration on NAB. Methods. Ten male volunteers without Helicobacter pylori infection received four different 14-day regimens of rabeprazole and ranitidine (study a, morning dose of 20mg rabeprazole; study b, morning dose of 20mg rabeprazole with a single bedtime dose of 150mg ranitidine only on the last day; study c, continuous 20mg morning dose of rabeprazole and 150mg at bedtime; study d, morning and evening doses of 10mg rabeprazole). Ambulatory 24-h gastric pH monitoring was conducted on the last day of each regimen. Results. NAB in studies a, b, c, and d was observed in 9, 1, 4, and 4 subjects, respectively, and the longest periods of nocturnal gastric pH at less than 4.0 were 102.5, 14.0, 37.5, and 52.5min, respectively (study b vs study c, P < 0.05). Conclusions. The continuous inhibitory effect of ranitidine combined with rabeprazole on nocturnal gastric acid secretion declined during 14-day-long administration in H. Pylori-negative subjects. Split dosing of rabeprazole was more effective than the single morning dose for inhibiting nocturnal gastric acid secretion.     

Helicobacter pylori gastritis and gastric physiology

It is now recognized that Helicobacter pylori infection exerts profound and diverse effects on gastric acid secretory function and that the alterations in acid secretion depend on the pattern of gastritis caused by the infection. In patients with an antral predominant nonatrophic gastritis, there is acid hypersecretion leading to duodenal ulcer disease. In patients with an atrophic pangastritis, there is markedly reduced acid secretion and increased risk for gastric cancer. It is now recognized that acid secretion also modifies H. pylori gastritis and a person's premorbid acid secretory status may be an important factor in determining the pattern of gastritis that an individual develops. This two-way interaction between H. pylori gastritis and gastric acid secretion is important in understanding the role of H. pylori infection in the response to proton-pump inhibitor therapy: It explains the more profound control of gastric acid secretion in H. pylori-positive patients and why rebound acid hypersecretion is confined to H. pylori-negative subjects.     

Gastric acid secretion of normal Japanese subjects in relation to Helicobacter pylori infection, aging, and gender

BACKGROUND: In Japan, where the incidence of gastric cancer is high, Helicobacter pylori infection could affect gastric acid secretion differently from that in Western countries. The aim of this study was to investigate the relationship between H. pylori infection, acid secretion, aging, and gender in normal Japanese subjects. METHODS: The study comprised 193 Japanese subjects who had undergone routine endoscopy. Gastrin-stimulated acid output was performed during the routine endoscopic examination using the endoscopic method of gastric acid secretory testing (EGT: endoscopic gastrin test), which has been reported previously. H. pylori status was determined by histology, rapid urease test, and serology. RESULTS: Mean EGT values were 3.9 +/- 1.5 mEq/10 min in H. pylori-negative men, 1.6 +/- 2.5 in H. pylori-positive men, 2.2 +/- 0.9 in H. pylori-negative women, and 1.5 +/- 1.2 in H. pylori-positive women. Although acid secretion was lower in H. pylori-positive subjects compared with H. pylori-negative subjects in both men and women, the decrease was more marked in men with H. pylori infection. Multiple linear regression analysis showed that aging is positively associated with gastric acid secretion in the H. pylori-negative subjects, whereas a negative association was found between them in the H. pylori-positive subjects. CONCLUSIONS: In Japanese subjects, aging affects gastric acid secretion differently depending on the status of H. pylori infection. H. pylori infection showed a stronger inhibitory effect on the acid secretion in men than in women. This gender-related difference in the susceptibility of acid secretion to H. pylori infection may explain the higher rates of gastric cancer in men in Japan.     

Intragastric volatile N-nitrosamines, nitrite, pH, and Helicobacter pylori during long-term treatment with omeprazole

BACKGROUND & AIMS: This study evaluated the effect of long-term gastric acid suppressive therapy with omeprazole on intragastric levels of carcinogenic N-nitrosamines and related parameters. METHODS: Forty-five patients on long-term omeprazole medication (mean, 35 months) and 13 healthy subjects without medication participated. Volatile N-nitrosamines were determined in gastric juice and urine. Intragastric pH, nitrite, nitrate, and H. pylori status were determined. DNA isolated from gastric biopsy specimens was analyzed for precarcinogenic alkyl-DNA adducts. RESULTS: The intragastric pH in patients was significantly higher compared with controls (P = 0.0001). Gastric nitrite levels in patients were nonsignificantly higher. There was no difference in total levels of intragastric volatile N-nitrosamines between patients and controls, however, urinary N-nitrosodimethylamine excretion was higher in patients (P = 0.001). On omeprazole, Helicobacter pylori-positive vs. -negative patients had a nonsignificantly higher intragastric nitrite level and higher urinary N-nitrosodimethylamine excretion. No alkyl-DNA adducts could be detected in gastric epithelium. CONCLUSIONS: Increased intragastric pH caused by long-term treatment with omeprazole does not result in increased intragastric levels of nitrite and volatile N-nitrosamines. The significantly higher urinary N-nitrosamine excretion implies the risk of increased endogenous formation of N-nitrosamines during long-term omeprazole treatment. This risk may be higher in H. pylori-positive patients.     

Effect of age and Helicobacter pylori infection on gastric acid secretion

BACKGROUND: Whether gastric acid secretion decreases with age is still controversial. With the discovery of Helicobacter pylori, the association of this bacterium with gastric acid secretion has also been discussed. The aim of this study was to investigate the relationship between gastric acid secretion, age and H. pylori infection. METHODS: The presence of H. pylori infection, the grade of fundic atrophic gastritis (FAG), and gastric acid secretion were investigated in 280 subjects without localized lesions in the upper gastrointestinal tract. Helicobacter pylori infection was confirmed by Giemsa and immunohistochemical staining, and FAG of biopsy specimens was graded on a scale of 0-4. RESULTS: Both basal and maximal acid output decreased with age in H. pylori-positive subjects, while they did not change with age in H. pylori-negative subjects. Gastric acid secretion decreased with the progression of FAG. An age-correlated decrease in gastric acid secretion in H. pylori-positive subjects depended on an increasing prevalence of FAG with age. CONCLUSIONS: In the population studied, advancing age had no influence on gastric acid secretion in H. pylori-negative subjects. Gastric acid secretion decreases with age in H. pylori-positive subjects because of the increasing prevalence of FAG with age.     

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.     

Successful platelet recovery after the second eradication of Helicobacter pylori with metronidazole in two patients with chronic idiopathic thrombocytopenic purpura

There are many reports on the efficacy of Helicobacter pylori (H. pylori) eradication therapy in patients with H. pylori-positive chronic idiopathic thrombocytopenic purpura (ITP). We administrated metronidazole (MNZ), amoxicillin (AMPC), and a proton-pump inhibitor (PPI) as the second eradication therapy for two patients who failed in the first eradication therapy consisting of PPI, AMPC, and clarithromycin (CAM). Successful eradication and the rapid recovery of platelet counts within one month were achieved in both patients. Recently, H. pylori eradication is considered as the first-line therapy for H. pylori-positive chronic ITP patients. In Japan, the PPI + AMPC + CAM regimen is recognized as the standard eradication therapy for H. pylori. However, the PPI + AMPC + MNZ regimen is also useful for eradication and should be tried as the re-treatment regimen after failure of the first-line CAM-containing regimen.     

Polymorphism of interleukin-1beta affects the eradication rates of Helicobacter pylori by triple therapy.

BACKGROUND AND AIMS: Polymorphism in interleukin-1beta (IL-1beta) is associated with intragastric pH levels in Helicobacter pylori-positive subjects. Intragastric pH levels affect the activity of antibiotics against H. pylori in the stomach. The aim of this study was to investigate whether IL-1beta polymorphism is associated with eradication rates of H. pylori by triple therapy with a proton pump inhibitor (PPI), amoxicillin, and clarithromycin. METHODS: Three hundred thirty-six patients infected with H. pylori completed treatment with omeprazole, 20 mg, or lansoprazole, 30 mg twice daily; clarithromycin, 200 mg 3 times daily; and amoxicillin, 500 mg 3 times daily, for 1 week. IL-1beta-511 and CYP2C19 genotypes of patients and sensitivity of H. pylori to clarithromycin and amoxicillin were determined. RESULTS: Logistic regression analysis showed that the IL-1beta-511 polymorphism, as well as CYP2C19 genotype of patients and clarithromycin-resistance of H. pylori, was associated with successful eradication. Eradication rates for H. pylori were 77.3% (75 of 97; 95% confidence interval, 67.5-84.6), 89.6% (147 of 164; 95% confidence interval, 83.9-93.1), and 94.7% (95% confidence interval, 86.9-98.5) in patients with the C/C, C/T, and T/T genotypes of IL-1beta-511, respectively (P = 0.0014). CONCLUSIONS: IL-1beta-511 polymorphism is one of the determinants of successful eradication of H. pylori using triple therapy with a PPI, amoxicillin, and clarithromycin, together with CYP2C19 genotype and bacterial resistance to clarithromycin.     

Acid-suppressive effects of rabeprazole: Comparing 10 mg and 20 mg twice daily in Japanese Helicobacter pylori-negative and -positive CYP2C19 extensive metabolisers

BACKGROUND: Rabeprazole 10mg b.i.d. is often administered as therapy for eradication of Helicobacter pylori (H. pylori) and is also proposed as therapy for refractory gastro-oesophageal reflux disease. However, there has not been a comprehensive assessment of its acid-suppressive effects. AIMS: To compare the acid-suppressive effects of rabeprazole 10mg b.i.d. with 20mg b.i.d. considering H. pylori status. SUBJECTS: Thirteen H. pylori-negative and eleven H. pylori-positive Japanese CYP2C19 extensive metabolisers (<35 years). METHODS: Intragastric pH was measured for 24h three times in a randomised manner; on day 7 of the repeated administration of rabeprazole 10mg b.i.d. or 20mg b.i.d., or a placebo. RESULTS: In median intragastric pH value and percent time of pH>3.0, >4.0, >5.0, >6.0, and >7.0 for 24h, no significant differences were observed between the two doses in either H. pylori-negative or H. pylori-positive subjects. At either dose, these parameters were significantly higher in H. pylori-positive subjects than in H. pylori-negative subjects. Nocturnal acid breakthrough occurred in seven and two of the thirteen H. pylori-negative subjects and one and two of the eleven H. pylori-positive subjects at each dose, respectively. CONCLUSIONS: The effects of rabeprazole 10mg b.i.d. were equal to those of 20mg b.i.d. in H. pylori-positive subjects; whereas in H. pylori-negative subjects, 20mg b.i.d. was superior for prevention of nocturnal acid breakthrough.     

夜间酸突破研究进展

夜间酸突破现象(NAB)在应用质子泵抑制剂的人群中有很高的发生率,发生机制复杂,其与反流性食管炎、Barrett'食管等酸相关性疾病的关系和治疗原则是近年来研究的热点.已有研究发现NAB的发生和食管酸暴露关系不大;睡前加服H2受体拮抗剂能减少NAB的发生,但疗效短暂;根除幽门螺杆菌会加重NAB的发生;肝药酶CYP2C19基因多态性对NAB发生率产生影响.