消溃汤配合西药治疗消化性溃疡60例

目的:观察中西医结合治疗消化性溃疡的疗效。方法:将120例消化性溃疡患者随机分为治疗组和对照组,治疗组60例,在常规西药抑酸抗菌治疗的基础上加用中药自拟消溃汤(黄芪、白术、陈皮、香附、丹参、延胡索、乌贼骨、白芍、甘草等)治疗;对照组60例,采用常规西药抑酸抗菌治疗。结果:治疗组总有效率95%,对照组总有效率70%,治疗组疗效优于对照组,两组比较有显著性差异。提示:中西医结合治疗消化性溃疡优于单纯西药治疗。

Comparative study of omeprazole, lansoprazole, pantoprazole and esomeprazole for symptom relief in patients with reflux esophagitis

AIM: To clarify whether there is any difference in the symptom relief in patients with reflux esophagitis following the administration of four Proton pump inhibitors (PPIs). METHODS: Two hundred and seventy-four patients with erosive reflux esophagitis were randomized to receive 8 wk of 20 mg omeprazole (n = 68), 30 mg of lansoprazole (n = 69), 40 mg of pantoprazole (n = 69), 40 mg of esomeprazole (n = 68) once a day in the morning. Daily changes in heartburn and acid reflux symptoms in the first 7 d 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 treated with esomeprazole more rapidly decreased than those receiving other PPI. Complete resolution of heartburn was also more rapid in patients treated with esomeprazole for 5 d compared with omeprazole (P = 0.0018, P = 0.0098, P = 0.0027, P = 0.0137, P = 0.0069, respectively), lansoprazole (P = 0.0020, P = 0.0046, P = 0.0037, P = 0.0016, P = 0.0076, respectively), and pantoprazole (P = 0.0006, P = 0.0005, P = 0.0009, P = 0.0031, P = 0.0119, respectively). There were no significant differences between the four groups in the rate of endoscopic healing of reflux esophagitis at week 8. CONCLUSION: Esomeprazole may be more effective than omeprazole, lansoprazole, and pantoprazole for the rapid relief of heartburn symptoms and acid reflux symptoms in patients with reflux esophagitis.

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 = 24） or 40 mg esomeprazole （n = 22） 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.

Effect of omeprazole and domperidone on adult asthmatics with gastroesophageal reflux

AIM： To study the effect of combined omeprazole（Ome） and domperidone（Dom） therapy on asthma symptoms and pulmonary function in asthmatics with gastroesoph- ageal reflux. METHODS： We selected 198 asthmatics with gastro- esophageal reflux diagnosed by 24-h esophageal pH moni- toring to receive Ome 20 mg twice daily and Dom 10 mg three times daily or placebo for 16 wk （1：1 double-blind randomization）. Spirometry was done at baseline and after 16 wk of treatment. The primary outcome measures were： mean daily daytime and nighttime asthma symptom scores. Mean daily reflux symptom scores, albuterol use as rescue medication （number of puffs）, daytime and nighttime peak expiratory flow rate （PEFR）, postbronchodilator forced expiratory volume in 1 second （FEVl） and postbronchodilator forced vital capacity （FVC） were secondary outcome measures. RESULTS： Comparison of mean change from baseline between antireflux therapy and placebo groups revealed significant reduction in daytime asthma symptom score （17.4% vs 8.9 %）, nighttime asthma symptom score （19.6% vs 5.4%）, reflux symptom score （8.7% vs 1.6%） and rescue medication use （23.2% vs 3.1%） after antireflux therapy compared to mean change in placebo group （P 〈 0.001）. There was significant improvement in morning PEFR （7.9% vs 0.2%）, evening PEFR （9.8% vs 0.5%）, FEW （11.1% vs 3.78%） and FVC （9.3%vs 1.52%） in the antireflux therapy group compared to placebo on comparng the mean change from baseline after 16 wk （P 〈 0.01） CONCLUSION： Combined therapy with Ome and Dom in adult asthmatics with gastroesophageal reflux may be beneficial by reducing asthma symptoms, rescuing medi- cation use, and improving pulmonary function.

Esomeprazole tablet vs omeprazole capsule in treating erosive esophagitis

AIM: Esomeprazole, an oral S-form of omeprazole, has been a greater acid inhibitor over omeprazole in treating acid-related diseases. Only less published data is available to confirm its efficacy for Asian people. Therefore, a perspective, double-blind, randomized comparison of esomeprazole tablets 40 mg (Nexium(?)) vs omeprazole capsules 20 mg (Losec(?)) in treating Chinese subjects with erosive/ulcerative reflux esophagitis (EE) was conducted. METHODS: A total of 48 EE patients were enrolled and randomized into two treatment groups under 8-wk therapy: 25 receiving esomeprazole, while another 23 receiving omeprazole treatment. Finally, 44 completed the whole 8-wk therapy. RESULTS: The difference in healing EE between two groups was 22.7% (72.7% vs 50.0%), not reaching significant value (P = 0.204). The median of the first time needed in relieving heartburn sensation was 1 d for both groups and the remission rates for heartburn on the 1st d after treatment were 77.3% and 65%, respectively (NS). The scores of various reflux relieving symptoms evaluated either by patients or by investigators were not different. Regarding drug safety, 28% of esomeprazole group and 26.1% of omeprazole group reported at least one episode of adverse effects, while constipation and skin dryness were the common side effects in both groups (NS). CONCLUSION: Esomeprazole 40 mg is an effective and safe drug at least comparable to omeprazole in treating Chinese EE patients.

Diagnosis of Zollinger-Ellison syndrome:Increasingly difficult

In the present paper the increasing difficulty of diag-nosis of Zollinger-Ellison syndrome (ZES) due to issues raised in two recent papers is discussed. These issues involve the difficulty and need to withdraw patients suspected of ZES from treatment with Proton Pump Inhibitors (omeprazole, esomeprazole, lansoprazole, rabeprazole, pantoprazole) and the unreliability of many gastrin radioimmunoassays. The clinical context of each of these important issues is reviewed and the conclusions in these articles commented from the per-spective of clinical management.

Omeprazole maintenance therapy prevents recurrent ulcer bleeding after surgery for duodenal ulcer

AIM： To evaluate the omeprazole maintenance therapy in patients with recurrent ulcer bleeding after surgery for duodenal ulcer. METHODS： We studied 15 consecutive patients with recurrent ulcer bleeding after surgery for duodenal ulcer. Omeprazole （20 mg/d） maintenance therapy was given after ulcer healing. In addition to clinical follow-up, ambulatory 24-h gastric pH assay was performed before and during omeprazole therapy in those patients and controls with previous duodenal ulcer surgery but no ulcer recurrence. RESULTS： All the 15 ulcers were healed after being treated with omeprazole （40 mg/d） for 2 too. Eleven patients with two （1-9） episodes of recurrent ulcer bleeding completed the follow-up （43, 12-72 too）. None of them had a bleeding episode while on omeprazole. One patient discontinued the therapy and had recurrent bleeding. The median 24-h fraction time of gastric pH 〈4 in patients was 80, 46-95%, and was reduced to 32, 13-70% by omeprazole （P= 0.002）. CONCLUSION： Long-term maintenance therapy with omeprazole （20 rag/day） is effective in preventing recurrent ulcer bleeding.

Effect of omeprazole on symptoms and ultrastructural esophageal damage in acid bile reflux

AIM: To value whether omeprazole could induce the healing of DIS and regression of symptoms in patients with DGER. METHODS: We enrolled 15 symptomatic patients with a pathological esophageal 24-h pH-metry and bilimetry. Patients underwent endoscopy and biopsies were taken from the distal esophagus. Specimens were analyzed at histology and transmission electron microscopy (TEM). Patients were treated with omeprazole 40 mg/d for 3 mo and then endoscopy with biopsies was repeated. Patients with persistent heartburn and/or with an incomplete recovery of DIS were treated for 3 more months and endoscopy with biopsies was performed. RESULTS: Nine patients had a non-erosive reflux disease at endoscopy (NERD) while 6 had erosive esophagitis (ERD). At histology, of the 6 patients with erosive esophagitis, 5 had mild esophagitis and 1 moderate esophagitis. No patients with NERD showed histological signs of esophagitis. After 3 mo of therapy, 13/15 patients (86.7%,P<0.01) showed a complete recovery of DIS and disappearance of heartburn. Of the 2 patients treated for 3 more months, complete recovery of DIS and heartburn were achieved in one. CONCLUSION: Three or 6 mo of omeprazole therapy led to a complete regression of the ultrastructural esophageal damage in 86.7% and in 93% of patients with DGER, NERD and ERD respectively. The ultrastructural recovery of the epithelium was accompanied by regression of heartburn in all cases.

Inhibition of gastric perception of mild distention by omeprazole in volunteers

AIM： To evaluate the effects of omeprazole on gastric mechanosensitivity in humans. METHODS： A double lumen polyvinyl tube with a plas- tic bag was introduced into the stomach of healthy volunteers under fluorography and connected to a barostat device. Subjects were then positioned so they were sitting comfortably, and the minimal distending pressure （MDP） was determined after a 30-rain adap- tation period. Isobaric distensions were performed in stepwise increments of 2 mmHg （2 min each） starting from the MDR Subjects were instructed to score feel- ings at the end of every step using a graphic rating scale： 0, no perception; 1, weak/vague; 2, weak but significant; 3, moderate/vague; 4, moderate but signifi- cant; 5, severe discomfort; and 6, unbearable pain. Af- ter this first test, subjects received omeprazole （20 mg, after dinner） once daily for 1 wk. A second test was performed on the last day of treatment. RESULTS： No adverse effects were observed. Mean MDP before and after treatment was 6.3 - 0.3 mmHg and 6.2：1：0.5 mmHg, respectively. One subject before and 2 after treatment did not reach a score of 6 at the maximum bag volume of 750 mL. After omeprazole, there was a significant increase in the distension pres- sure required to reach scores of 1 （P = 0.019） and 2 （P = 0.017） as compared to baseline. There were no changes in pressure required to reach the other scores after treatment. Two subjects before and one after omeprazole rated their abdominal feeling 〈 1 at MDP, and mean （±SE） abdominal discomfort scores at MDP were 0.13±0.09 and 0.04±0.04, respectively. Mean scores induced by each MDP ＋ 2, 4, 6, 8, 10, 12, 14, 16, 18 and 20 （mmHg） were 1.1±0.3, 2.0±0.4, 2.9±0.5, 3.3±0.4, 4.6±0.3, 5.2±0.3, 5.5±0.2, 5.5±0.3, 5.7±0.3, and 5.4, respectively. After omepra- zole, abdominal feeling scores for the same incremen- tal pressures over MDP were 0.3±0.1, 0.8±0.1, 2.0±0.4, 2.8±0.4, 3.8±0.4, 4.6±0.4, 4.9±0.3, 5.4±0.4, 5.2±0.6, and 5.0±1.0, respectively. A signif- icant decrease in feeling score was observed at intra- bag pressures of MDP ＋ 2 mmHg （P = 0.028） and ＋ 4 mmHg （P = 0.013）, respectively, after omeprazole. No significant score changes were observed at pres- sures ≥ MDP ＋ 6 mmHg. CONCLUSION： Although the precise mechanisms are undetermined, the present study demonstrated that omeprazole decreases mechanosensitivity to mild gas- tric distension.

Omeprazole-based triple therapy with low-versus high-dose of clarithromycin plus amoxicillin for H pylori eradication in Iranian population

AIM： To investigate the efficacy and tolerability of H pylori eradication in an omeprazole-based triple therapy with high and low dose of clarithromycin and amoxicillin. METHODS： One hundred and sixty H pylori positive patients were randomly assigned to two groups based on the following 2 wk investigation; （1） group A or low-dose regimen received omeprazole 20 mg b.i.d, clarithromycin 250 mg b.i.d and amoxicillin 500 mg b.i.d; and （2） group B or high-dose regimen received omeprazole 20 mg b.i.d, clarithromycin 500 mg b.i.d and amoxicillin 1000 mg b.i.d. During the study Hpylori status was assessed by histology and rapid urease test prior and by 13C-urea breath test 6 wk after the therapy. Standard questionnaires were administered to determine the compliance to treatment and possible adverse events of therapy. Data were subject to x^2 to compare the eradication rates in the two groups. The significant level of 95% （P ≤ 0.05） was considered statistically different. RESULTS： We found that the per-protocol eradication rate was 88% （68/77） in group A, and 89% （67/75） in group B. The intension-to-treat eradication rate was 85% （68/80） in group A and 83.75% （67180） in group B. Overall adverse events were 26% in group A and 31% in group B. The adverse events were generally mild in nature and tolerated well in both groups with a compliance of 98% in group A vs 96% in group B. CONCLUSION： The omeprazole-based low dose regimen of darithromycin and amoxicillin for two weeks in Hpylori eradication is as effective as high dose regimen in Iranian population.

Efficacy of omeprazole and amoxicillin with either clarithromycin or metronidazole on eradication of Helicobacter pylori in Chinese peptic ulcer patients

AIM: One-week triple therapy with proton pump inhibitors, clarithromycin and amoxicillin has recently been proposed as the first-line treatment for Helicobacter pylori (H pylori) infection; however, data regarding the effects of this regimen in China are scarce. The aim of this prospective and randomized study was to compare the efficacy of clarithromycin and metronidazole when they were combined with omeprazole and amoxicillin on eradication of H pylori and ulcer healing in Chinese peptic ulcer patients. METHODS: A total of 103 subjects with Hpylori-positive peptic ulcer were randomly divided into two groups, and accepted triple therapy with omeprazole 20 mg, amoxicillin 1 000 mg and either clarithromycin 500 mg (OAC group, n = 58) or metronidazole 400 mg (0AM group, n - 45). All drugs were given twice daily for 7 d. Patients with active peptic ulcer were treated with omeprazole 20 mg daily for 2-4 wk after anti-H pylori therapy. Six to eight weeks after omeprazole therapy, all patients underwent endoscopies and four biopsies (two from the antrum and two others from the corpus of stomach) were taken for rapid urease test and histological analysis (with modified Giemsa staining) to examine H pylori. Successful eradication was defined as negative results from both examination methods. RESULTS: One hundred patients completed the entire course of therapy and returned for follow-up. The eradication rate of H pylori for the per-protocol analysis was 89.3% (50/56) in OAC group and 84.1% (37/44) in 0AM group. Based on the intention-to-treat analysis, the eradication rate of H pylori was 86.2% (50/58) in OAC group and 82.2% (37/45) in 0AM group. There were no significant differences in eradication rates between the two groups on either analysis. The active ulcer-healing rate was 96.7% (29/30) in OAC group and 100% (21/21) in 0AM group (per-protocol analysis, P>0.05). Six patients in OAC group (10.3%) and five in OAM group (11.1%) reported adverse events (P>0.05). CONCLUSION: One-week triple therapy with omeprazole and amoxicillin in combination with either clarithromycin or metronidazole is effective for the eradication of H pylori. The therapeutic regimen comprising metronidazole with low cost, good compliance and mild adverse events may offer a good choice for the treatment of peptic ulcers associated with H pylori infection in China.

Clopidogrel and proton pump inhibitors-where do we stand in 2012?

Clopidogrel in association with aspirine is considered state of the art of medical treatment for acute coronary syndrome by reducing the risk of new ischemic events.Concomitant treatment with proton pump inhibitors in order to prevent gastrointestinal side effects is recommended by clinical guidelines.Clopidogrel needs metabolic activation predominantly by the hepatic cytochrome P450 isoenzyme Cytochrome 2C19(CYP2C19) and proton pump inhibitors(PPIs) are extensively metabolized by the CYP2C19 isoenzyme as well.Several pharmacodynamic studies investigating a potential clopidogrel-PPI interaction found a significant decrease of the clopidogrel platelet antiaggregation effect for omeprazole,but not for pantoprazole.Initial clinical cohort studies in 2009 reported an increased risk for adverse cardiovascular events,when under clopidogrel and PPI treatment at the same time.These observations led the United States Food and Drug Administration and the European Medecines Agency to discourage the combination of clopidogrel and PPI(especially omeprazole) in the same year.In contrast,more recent retrospective cohort studies including propensity score matching and the only existing randomized trial have not shown any difference concerning adverse cardiovascular events when concomitantly on clopidogrel and PPI or only on clopidogrel.Three meta-analyses report an inverse correlation between clopidogrel-PPI interaction and study quality,with high and moderate quality studies not reporting any association,rising concern about unmeasured confounders biasing the low quality studies.Thus,no definite evidence exists for an effect on mortality.Because PPI induced risk reduction clearly overweighs the possible adverse cardiovascular risk in patients with high risk of gastrointestinal bleeding,combination of clopidogrel with the less CYP2C19 inhibiting pantoprazole should be recommended.

A head to head comparison of oral vs intravenous omeprazole for patients with bleeding peptic ulcers with a clean base,flat spots and adherent clots

AIM： To compare the effect of intravenous and oral omeprazole in patients with bleeding peptic ulcers without high-risk stigmata.METHODS： This randomized study included 211 patients [112 receiving iv omeprazole protocol （Group 1）, 99 receiving po omeprazole 40 mg every 12 h （Group 2）] with a mean age of 52.7. In 144 patients the ulcers showed a clean base, and in 46 the ulcers showed fiat spots and in 21 old adherent clots. The endpoints were re-bleeding, surgery, hospital stay, blood transfusion and death. After discharge, re-bleeding and death were reevaluated within 30 d.RESULTS： The study groups were similar with respect to baseline characteristics. Re-bleeding was recorded in 5 patients of Group 1 and in 4 patients of Group 2 （P = 0.879）. Three patients in Group 1 and 2 in Group 2 underwent surgery （P = 0.773）. The mean length of hospital stay was 4.6 ± 1.6 d in Group 1 vs 4.5 ± 2.6 d in Group 2 （P = 0.710）; the mean amounts of blood transfusion were 1.9 ±1.1 units in Group 1 vs 2.1 ±1.7 units in Group 2 （P = 0.350）. Four patients, two in each group died （P = 0.981）. After discharge, a new bleeding occurred in 2 patients of Group 1 and in 1 patient of Group 2, and one patient from Group 1 died.CONCLUSION： We demonstrate that the effect of oral omeprazole is as effective as intravenous therapy in terms of re-bleeding, surgery, transfusion requirements, hospitalization and mortality in patients with bleeding ulcers with low risk stigmata. These patients can be treated effectively with oral omeprazole.

Long-term treatment with proton pump inhibitor is associated with undesired weight gain

AIM:To examine the effects of long-term proton pump inhibitor (PPI) therapy on body weight (BW) and body mass index (BMI) in patients with gastroesophageal reflux disease (GERD).METHODS: The subjects were 52 patients with GERD and 58 sex-and age-matched healthy controls. GERD patients were treated with PPI for a mean of 2.2 years (range, 0.8-5.7 years), and also advised on lifestyle modifications (e.g. selective diet, weight management). BW, BMI and other parameters were measured at baseline and end of study.RESULTS: Twenty-four GERD patients were treated daily with 10 mg omeprazole, 12 with 20 mg omeprazole, 8 with 10 mg rabeprazole, 5 with 15 mg lansoprazole, and 3 patients with 30 mg lansoprazole. At baseline, there were no differences in BW and BMI between reflux patients and controls. Patients with GERD showed increases in BW (baseline: 56.4±10.4 kg, end: 58.6±10.8 kg, mean±SD, P<0.0001) and BMI (baseline: 23.1±3.1 kg/m2, end: 24.0±3.1 kg/m2, P<0.001), but no such changes were noted in the control group. Mean BW increased by 3.5 kg (6.2% of baseline) in 37 (71%) reflux patients but decreased in only 6 (12%) patients during treatment.CONCLUSION: Long-term PPI treatment was associated with BW gain in patients with GERD. Reflux patients receiving PPI should be encouraged to manage BW through lifestyle modifi cations.

Early effects of oral administration of omeprazole and roxatidine on intragastric pH

Objective： The ideal medication for the treatment of acid-related diseases, e.g., peptic ulcers, stress- related gastric bleeding, functional dyspepsia, and gastroesophageal reflux disease, should have a rapid onset of action to promote hemostasis and relieve the symptoms. The aim of our study was to investigate the inhibitory effects on gastric acid secretion of a single oral administration of a proton pump inhibitor, omeprazole 20 mg, and an H2-receptor antagonist, roxatidine 75 mg. Methods： Ten Heficobacterpylori-negative male subjects participated in this randomized, two-way crossover study. Intragastric pH was monitored continuously for 6 h after single oral admini- stration of omeprazole 20 mg and roxatidine 75 mg. Each administration was separated by a 7-d washout period. Results： During the 6-h study period, the average pH after administration of roxatidine was higher than that after administration of omeprazole （median： 4.45 vs. 2.65; P=0.0367）. Also during the 6-h study period, a longer duration of maintenance at pH above 2, 5, and 6 was observed after administration of roxatidine 75 mg than after administration of omeprazole 20 mg （median： 90.6% vs. 55.2%, P=-0.0284; 43.7% vs. 10.6%, P=0.0125; 40.3% vs. 3.3%, P=0.0125; respectively）. Conclusions： In Helicobacter pylori-negative healthy male subjects, oral administration of roxatidine 75 mg increased the intragastric pH more rapidly than that of omeprazole 20 mg.

Relative bioavailability and pharmacokinetic comparison of two different enteric formulations of omeprazole

In order to comply with the requirements for a drug listed in China, the study was developed to compare the pharmacokinetics and relative bioavailability of two different enteric formulations of omeprazole (OPZ) in healthy Chinese subjects. A total of 32 volunteers participated in the study. Plasma concentrations were analyzed by non- stereospecific liquid chromatography/tandem mass spectrometric (LC-MS/MS) method. After administration of a single 40-mg dose of the two OPZ formulations, the comparative bioavailability was assessed by calculating individual AUC0-t (the area under the concentration-time curve from time zero to the last measurable concentration), AUC0-∞ (the area under the concentration-time curve extrapolated to infinity), Cmax (the maximum observed concentration), and Tpeak (the time to Cmax) values of OPZ, 5-hydroxyomeprazole (OH-OPZ), and omeprazole sulfone (OPZ-SFN), respectively. The 90% confidence intervals (CIs) of AUC0-t, AUC0-∞, and Cmax were 85.4%-99.0%/88.8%-98.6%/87.6%-99.4%, 85.5%-99.2%/89.0%-98.6%/88.5%-101.3%, and 72.3%-87.6%/79.6%-91.1%/88.4%-99.1% for OPZ/OH-OPZ/ OPZ-SFN, respectively, and Tpeak values did not differ significantly. In this study, the test formulation of OPZ in fasting healthy Chinese male volunteers met the Chinese bioequivalance standard to the reference formulation based on AUC, Cmax, and Tpeak.