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Pump Inhibitors (pump + inhibitor)
Kinds of Pump Inhibitors Terms modified by Pump Inhibitors Selected AbstractsRecent Use of Proton Pump Inhibitor-Based Triple Therapies for the Eradication of H. pylori: A Broad Data ReviewHELICOBACTER, Issue 2 2003Hans-Joachim Ulmer abstract Introduction. For the eradication of Helicobacter pylori a 1-week triple therapy combining proton pump inhibitors with two antibiotics has been recommended as a gold standard therapy. However, a recent broad data review on the efficacy of the different regimens is missing. Therefore, the aim of this study was to systematically review the recent literature. Methods. We undertook a broad data review of the efficacy of nine different 7-day triple therapies consisting of a proton pump inhibitor (lansoprazole, pantoprazole, omeprazole) in its standard dosage and two antibiotics. Relevant original papers on H. pylori eradication in adults, published in English or German between 1995 and 2000, were identified from MEDLINE searches. Studies were reviewed and selected according to predefined criteria. Results. Our predefined criteria were fulfilled by 79 full paper articles including 112 study arms with 8383 patients on intention-to-treat, or 6787 patients on per-protocol basis, respectively. The mean eradication rates unweighted or weighted by the number of patients in the study arm vary from 71.9% to 83.8% for intention-to-treat analysis and from 78.5% to 91.2% for per-protocol analysis. Conclusions. All nine PPI based triple therapy regimens are very effective in H. pylori eradication. The current literature review underlines that the use of either lansoprazole, omeprazole, or pantoprazole combined with two antibiotics yield similar high eradication rates. [source] The Choice of a Proton Pump InhibitorBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2004Ove B. Schaffalitzky de Muckadell [source] The Choice of Proton Pump Inhibitor: Does it matter?BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2004Per M. Hellström Comparisons of four different proton pump inhibitors: lansoprazole, omeprazole, pantoprazole, and rabeprazole show that they all have similar potency and efficacy. Rabeprazole, however, displays a slightly more rapid onset of acid inhibition than the others; the clinical advantage of this seems limited. The S-isomer of omeprazole, esomeprazole, exhibits a somewhat higher potency than the other proton pump inhibitors. Reports supporting a clinical advantage of this property are not convincing. To conclude, all inhibitors seem comparable as regards inhibition of gastric acid secretion. [source] Proton Pump Inhibitors and Helicobacter pylori Gastritis: Friends or Foes?BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2006Ernst J. Kuipers In H. pylori -positive patients, profound acid suppressive therapy induces a corpus-predominant pangastritis, which is associated with accelerated corpus gland loss and development of atrophic gastritis. Both corpus-predominant and atrophic gastritis have been associated with an increased risk of development of gastric cancer. H. pylori eradication leads to resolution of gastritis and may induce partial regression of pre-existent gland loss. H. pylori eradication does not aggravate GERD nor does it impair the efficacy of proton pump inhibitor maintenance therapy for this condition. This is the background of the advise within the European guidelines for the management of H. pylori infection to offer an H. pylori test and treat policy to patients who require proton pump inhibitor maintenance therapy for GERD. As such a policy fully reverses H. pylori pangastritis even in patients who have been treated for years with proton pump inhibitors, there is no need to eradicate H. pylori before the start of proton pump inhibitors. In fact, the somewhat slower initial response of H. pylori -negative GERD patients to proton pump inhibitor therapy and the fact that many GERD patients will only require short-term therapy suggests to first start the proton pump inhibitor, and only test and treat when maintenance therapy needs to be prescribed. Such considerations prevent the persistent presence of active corpus-predominant gastritis in proton pump inhibitor-treated reflux patients without impairing the clinical efficacy of treatment [source] CYP2C19 Polymorphism and Proton Pump InhibitorsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 1 2004Ulrich Klotz In different populations three phenotypes have been identified: extensive metabolizers, poor metabolizers and individuals carrying one wild type and one mutant allele (het extensive metabolizers). Systemic exposure to the proton pump inhibitors as expressed by the AUC (area under the plasma level time profiles) is 5,12-times higher in poor metabolizers than in extensive metabolizers. As the pharmacodynamic response (elevation of intragastric pH) to the proton pump inhibitors is related directly to their AUC, a much higher pH can be monitored over 24 hr in poor metabolizers than in extensive metabolizers. Furthermore, clinical efficacy of all proton pump inhibitors depend on maintaining intragastric pH above certain threshold levels and significantly higher eradication rates of Helicobacter pylori have been observed in patients of the poor metabolizers and het extensive metabolizers phenotype if compared to extensive metabolizers. Likewise, limited data suggest that proton pump inhibitors-induced healing rates in gastro-oesophageal reflux disease are apparently higher in poor metabolizers/het extensive metabolizers than in extensive metabolizers of CYP2C19. Therefore initial genotyping for this enzyme and higher dosage in extensive metabolizers is likely to improve the clinical efficacy of proton pump inhibitors. [source] Quinazolinone Fungal Efflux Pump Inhibitors.CHEMINFORM, Issue 3 2005Part 2. No abstract is available for this article. [source] Inter-observer agreement for multichannel intraluminal impedance,pH testingDISEASES OF THE ESOPHAGUS, Issue 7 2010K. Ravi SUMMARY Twenty-four-hour ambulatory multichannel intraluminal impedance (MII),pH detects both acid and nonacid reflux (NAR). A computer-based program (AutoscanÔ, Sandhill Scientific, Highlands Ranch, CO, USA) automates the detection of reflux episodes, increasing the ease of study interpretation. Inter-observer agreement between multiple reviewers and with AutoscanÔ for the evaluation of significant NAR with MII,pH has not been studied in the adult population. Twenty MII,pH studies on patients taking a proton pump inhibitor twice daily were randomly selected. AutoscanÔ analyzed all studies using the same pre-programmed parameters. Four reviewers interpreted the MII,pH studies, adding or deleting reflux episodes detected by AutoscanÔ. Positive studies for NAR and total reflux episodes were based on published criteria. Cohen's kappa statistic (,) evaluated inter-observer agreement between reviewers and AutoscanÔ analysis. The average , for pathologic NAR between reviewers was 0.57 (0.47,0.70), and between reviewers and AutoscanÔ was 0.56 (0.4,0.8). When using the total reflux episode number as a marker for pathologic reflux (acid and NAR), the , score was 0.72 (0.61,0.89) between reviewers, and 0.74 (0.53,0.9) when evaluating total reflux episodes. Two reviewers agreed more often with each other and with AutoscanÔ on the number of NAR episodes, while the other two reviewers agreed with each other, but did not agree with either AutoscanÔ or the first two reviewers. Inter-observer agreement between reviewers and AutoscanÔ for detecting pathologic NAR is moderate, with reviewers either excluding more of the AutoscanÔ-defined events or excluding fewer events and therefore agreeing with AutoscanÔ. [source] Econazole-induced Ca2+ fluxes and apoptosis in human oral cancer cellsDRUG DEVELOPMENT RESEARCH, Issue 4 2010Daih-Huang Kuo Abstract The effect of econazole on cytosolic free Ca2+ concentrations ([Ca2+]i) and viability was explored in human oral cancer cells (OC2), using the fluorescent dyes fura-2 and WST-1, respectively. Econazole at concentrations of >1,µM increased [Ca2+]i in a concentration-dependent manner. The Ca2+ signal was reduced partly by removing extracellular Ca2+. The econazole-induced Ca2+ influx was sensitive to blockade of aristolochic acid (phospholipase A2 inhibitor) and GF109203X (PKC inhibitor). In Ca2+ -free medium, after treatment with 1,µM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor), 30,µM econazole failed to induce a [Ca2+]i rise. Inhibition of phospholipase C with 2,µM U73122 substantially suppressed econazole-induced [Ca2+]i rise. At concentrations of 5,70,µM econazole killed cells in a concentration-dependent manner. The cytotoxic effect of 50,µM econazole was enhanced by prechelating cytosolic Ca2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N,,N,-tetraacetic acid (BAPTA). The ERK MAPK inhibitor, PD98059 (10,µM), also enhanced 20,µM econazole-induced cell death. Propidium iodide staining data suggest that econazole induced apoptosis between concentrations of 10,70,µM. Collectively, in OC2 cells, econazole induced [Ca2+]i rises by causing Ca2+ release from the endoplasmic reticulum and Ca2+ influx from phospholipase A2/PKC-regulated Ca2+ channels. Furthermore, econazole caused cell death appeared to be regulated by ERK MAPK. Drug Dev Res 71: 240,248, 2010. © 2010 Wiley-Liss, Inc. [source] Nonylphenol-induced cytosolic Ca2+ elevation and death in renal tubular cellsDRUG DEVELOPMENT RESEARCH, Issue 5 2009Jeng-Yu Tsai Abstract Nonylphenol is an environmental endocrine disrupter. The effect of nonylphenol on intracellular free Ca2+ levels ([Ca2+]i) and viability in Madin-Darby canine kidney (MDCK) cells was explored. Nonylphenol increased [Ca2+]i in a concentration-dependent manner (EC50,0.8,,M). Nonylphenol-induced Mn2+ entry demonstrated Ca2+ influx and removal of extracellular Ca2+ partly decreased the [Ca2+]i rise. The [Ca2+]i rise was inhibited by the protein kinase C activator, phorbol 13-myristate acetate (PMA) but not by L-type Ca2+ channel blockers. In Ca2+ -free medium, nonylphenol-induced [Ca2+]i rise was partly inhibited by pretreatment with 1,,M thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor). Conversely, nonylphenol pretreatment abolished thapsigargin-induced Ca2+ release. Nonylphenol-induced Ca2+ release was unaltered by inhibition of phospholipase C. At concentrations of 5,100,,M, nonylphenol killed cells in a concentration-dependent manner. The cytotoxic effect of 100,,M nonylphenol was not affected by preventing [Ca2+]i rises with BAPTA/AM. Collectively, this study shows that nonylphenol induced [Ca2+]i increase in MDCK cells via evoking Ca2+ entry through protein kinase C-regulated Ca2+ channels, and releasing Ca2+ from endoplasmic reticulum and other stores in a phospholipase C-independent manner. Nonylphenol also killed cells in a Ca2+ -independent fashion. Drug Dev Res, 2009. © 2009 Wiley-Liss, Inc. [source] IP3 receptor in the hair cells of frog semicircular canal and its possible functional roleEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2006Maria Lisa Rossi Abstract The presence and functional role of inositol trisphosphate receptors (IP3R) was investigated by electrophysiology and immunohistochemistry in hair cells from the frog semicircular canal. Intracellular recordings were performed from single fibres of the posterior canal in the isolated, intact frog labyrinth, at rest and during rotation, in the presence of IP3 receptor inhibitors and drugs known to produce Ca2+ release from the internal stores or to increase IP3 production. Hair cell immunolabelling for IP3 receptor was performed by standard procedures. The drug 2-aminoethoxydiphenyl borate (2APB), an IP3 receptor inhibitor, produced a marked decrease of mEPSP and spike frequency at low concentration (0.1 mm), without affecting mEPSP size or time course. At high concentration (1 mm), 2APB is reported to block the sarcoplasmic-endoplasmic reticulum Ca2+ -ATPase (SERCA pump) and increase [Ca2+]i; at the labyrinthine cytoneural junction, it greatly enhanced the resting and mechanically evoked sensory discharge frequency. The selective agonist of group I metabotropic glutamate receptors (RS)-3,5-dihydroxyphenylglycine (DHPG, 0.6 mm), produced a transient increase in resting mEPSP and spike frequency at the cytoneural junction, with no effects on mEPSP shape or amplitude. Pretreatment with cyclopiazonic acid (CPA, 0.1 mm), a SERCA pump inhibitor, prevented the facilitatory effect of both 2APB and DHPG, suggesting a link between Ca2+ release from intracellular stores and quantal emission. Consistently, diffuse immunoreactivity for IP3 receptors was observed in posterior canal hair cells. Our results indicate the presence and a possibly relevant functional role of IP3-sensitive stores in controlling [Ca2+]i and modulating the vestibular discharge. [source] Actions of Arachidonic Acid on Contractions and Associated Electrical Activity in Guinea-Pig Isolated Ventricular MyocytesEXPERIMENTAL PHYSIOLOGY, Issue 4 2001M. A. Mamas The actions of arachidonic acid (AA) were investigated in guinea-pig isolated ventricular myocytes. Exposure of myocytes to 10 ,M AA reduced the amplitude of contractions and calcium transients accompanying action potentials at a frequency of 1 Hz. AA (10 ,M) also reduced the amplitude of calcium currents recorded under voltage-clamp conditions. The suppression of contraction by AA was not prevented by either 10 ,M trihydroindomethicin (to inhibit cyclo-oxygenase) or 10 ,M ETYA (5,8,11,14-eicosatetraynoic acid, to inhibit AA metabolising enzymes), showing that the actions of AA appeared not to be mediated by these metabolites. The reduction of contraction by 10 ,M AA was also not prevented by the protein kinase C inhibitor, Ro31-8220 (1 ,M), showing that this pathway appeared not to be required for the observed effect. Direct effects of AA may be involved. A further action of 10 ,M AA was to suppress spontaneous electrical activity induced by either the ,-adrenergic agonist isoprenaline or the Na+ pump inhibitor, ouabain. This effect of AA on spontaneous activity might be associated with the observed reduction of calcium entry through L-type calcium channels, although additional effects of AA on calcium release from the sarcoplasmic reticulum might also be involved. [source] Annual Change of Primary Resistance to Clarithromycin among Helicobacter pylori Isolates from 1996 through 2008 in JapanHELICOBACTER, Issue 5 2009Noriyuki Horiki Abstract Background:, Recent studies have shown that the combination of proton pump inhibitor, amoxicillin and clarithromycin is one of the best choices for Helicobacter pylori eradication therapy. However, increasing number of cases of H. pylori infection showing resistance to clarithromycin therapy has been reported and this is currently the main cause of eradication failure. We investigated the annual changes of the antimicrobial susceptibility to clarithromycin, amoxicillin and minocycline during a period of 12 years in Japan. Methods:, This study comprised 3521 patients (mean age (SD), 55.4 (13.7) years-old, 2467 males and 1054 females) positive for H. pylori as assessed by microaerobic bacterial culture from 1996 through 2008. All patients were previously untreated for H. pylori and were enrolled in the study to assess primary resistance to the three antibiotics. Results:, The overall primary resistance to clarithromycin, amoxicillin and minocycline were 16.4%, (577/3521), 0.03% (1/3521) and 0.06% (2/3521), respectively. From1996 through 2004, the resistance rate to clarithromycin increased gradually to approximately 30% and then it remained without marked fluctuation since 2004. Analysis by gender showed a significant increase (p < .0001) in resistance rate to clarithromycin among females (217/1057, 20.6%) compared to males (360/2467, 14.6%). Analysis by age, disclosed significantly (p < .0001) higher resistance rate to clarithromycin in patients of more than 65-years-old compared to the younger population. Conclusions:, The resistance rate of H. pylori infection to clarithromycin in Japan has increased gradually to approximately 30% from 1996 through 2004, and remained unchanged since 2004. Elderly and females were at high risk of having resistance to clarithromycin. Our results suggested that the level of clarithromycin resistance in Japan has now risen to the point where it should no longer be used as empiric therapy. [source] Helicobacter pylori Eradication Therapy May Facilitate Gastric Ulcer Healing After Endoscopic Mucosal Resection: A Prospective Randomized StudyHELICOBACTER, Issue 6 2008Jae Hee Cheon Abstract Background and Aim:, It remains unclear whether Helicobacter pylori eradication therapy affects the healing rate of iatrogenic ulcers following endoscopic mucosal resection (EMR) for gastric tumors. The aim of our study was to prospectively evaluate the effect of H. pylori eradication therapy on gastric ulcer healing after EMR. Methods:, After EMR, patients were randomly assigned to either the H. pylori eradication group (Hp group) (lansoprazole 30 mg, amoxicillin 1000 mg, and clarithromycin 500 mg, twice a day for 7 days) or the noneradication group (proton pump inhibitor, PPI group) (lansoprazole 30 mg, twice a day for 7 days). Four weeks after EMR, the ulcer stages and size were compared between the two groups. Moreover, ulcer-related symptoms, bleeding rates, adverse effects, and drug compliance were compared. Results:, A total of 64 patients were enrolled. Of these, 17 patients were excluded from the study. The two groups were comparable in terms of baseline clinicopathologic characteristics. Four weeks after EMR, the two groups did not differ with respect to ulcer stage (p = .475) or ulcer-related symptoms (p = .399). However, the ulcer reduction ratio was significantly higher in the Hp group (0.028 ± 0.024 vs. 0.065 ± 0.055, p < .05). No differences were observed between the two groups with regard to drug compliance, adverse drug event rates, or bleeding rates. Conclusions:, Our results suggest that H. pylori eradication therapy might improve the ulcer healing rate after EMR. [source] Long-term Follow up of Helicobacter pylori IgG Serology After Eradication and Reinfection Rate of H. pylori in South KoreaHELICOBACTER, Issue 4 2008Jung Hoon Lee Abstract Background: Serology is widely used for epidemiologic research of Helicobacter pylori. However, there is limited information on the long-term follow up of H. pylori titers after eradication. In addition, it is presumed that the reinfection rate decreases as the H. pylori infection rate decreases. The aim of this study was to investigate the long-term follow up of H. pylori IgG, and to evaluate the reinfection rate of H. pylori in Korea. Methods: Among 247 patients, who were enrolled during 2003,07, 185 patients with invasive H. pylori test positive received proton pump inhibitor-based triple therapy, and follow-up H. pylori testing, including histology, CLOtest, culture, and serology, were evaluated 2, 10, and 18 months after H. pylori eradication. Results: The initial H. pylori IgG optical density (OD450nm), 2.06, gradually decreased to 0.63 (67% reduction) at 18 months after H. pylori eradication. The seroreversion rate was 5, 10, and 45% at 2, 10, and 18 months after H. pylori eradication, respectively. The recrudescence of H. pylori was 3.49%, and the annual reinfection rate was 2.94% per year. H. pylori IgG titers abruptly increased in cases with recrudescence and reinfection, and correlated with the results of the invasive H. pylori tests. Conclusion: The results of this study showed that H. pylori IgG serology could be used for the determination of reinfection of H. pylori, but not for the diagnosis of H. pylori eradication. The reinfection rate of H. pylori, in Korea, was found to be very low, 2.94% per year. [source] Rabeprazole- versus Esomeprazole-Based Eradication Regimens for H. pylori InfectionHELICOBACTER, Issue 6 2007I-Chen Wu Abstract Background: Different kinds of proton pump inhibitor-based triple therapies could result in different Helicobacter pylori eradication rates. Aim: The aims of this study were to compare the efficacy and safety of rabeprazole- and esomeprazole-based triple therapy in primary treatment of H. pylori infection in Taiwan. Patients and Methods: From June 2005 to March 2007, 420 H. pylori -infected patients were randomly assigned to receive a 7-day eradication therapy with either esomeprazole 40 mg daily (EAC group, n = 209) or rabeprazole 20 mg b.i.d. (RAC group, n = 211) in combination with amoxicillin 1 g b.i.d. and clarithromycin 500 mg b.i.d.. Follow-up endoscopy with biopsy was done 12,16 weeks after completion of eradication therapy. Those who refused endoscopic exams underwent 13C-urea breath test to assess the treatment response. Results: Intention-to-treat analysis revealed that the eradication rate was 89.4% in the EAC group and 90.5% in RAC groups (p -value = .72). All of the subjects returned for assessment of compliance (100% in EAC group vs. 99.5% in RAC group, p -value = .32) and adverse events (3.83% in EAC group vs. 6.16% in RAC group, p -value = .27). Sixty (28.7%) and 37 (17.6%) patients in EAC and RAC group, respectively, refused endoscopy and underwent a 13C-urea breath test to determine the treatment effect. Conclusion: In conclusion, rabeprazole- and esomeprazole-based primary therapies for H. pylori infection are comparable in efficacy and safety. [source] A Report Card to Grade Helicobacter pylori TherapyHELICOBACTER, Issue 4 2007David Y. Graham Helicobacter pylori causes a serious bacterial infectious disease, and the expectations of therapy should reflect this fact. Increasing antibiotic resistance, especially to clarithromycin, has significantly undermined the effectiveness of legacy triple therapy consisting of a proton pump inhibitor, clarithromycin, and amoxicillin. Current cure rates are consistently below 80% intention-to-treat, the accepted threshold separating acceptable from unacceptable treatment results. Grading clinical studies into effectiveness categories using prespecified criteria would allow clinicians to objectively identify and compare regimens. We offer a therapy report card similar to that used to grade the performance of school children. The intention-to-treat cure rate categories are: F or unacceptable ( 80%), D or poor (81,84%), C or fair (85,89%), B or good (90,95%), and A or excellent (95,100%). The category of "excellent" is based on the cure rates expected with other prevalent bacterial infectious diseases. We propose that only therapies that score "excellent" (grade = A) should be prescribed. Regimens scoring as B or "good" can be used if "excellent" results are not obtainable. In most regions legacy triple therapy should be abandoned as unacceptable. Quadruple therapy and sequential therapy are reasonable alternatives for initial therapy. [source] Helicobacter pylori"Rescue" Therapy After Failure of Two Eradication TreatmentsHELICOBACTER, Issue 5 2005Javier P. Gisbert ABSTRACT Nowadays, apart from having to know well first-line eradication regimens, we must also be prepared to face Helicobacter pylori treatment failures. Therefore, in designing a treatment strategy we should not focus on the results of primary therapy alone, but also on the final , overall , eradication rate. After failure of a combination of proton pump inhibitor (PPI), amoxicillin, and clarithromycin, the use of empirical quadruple therapy (PPI,bismuth,tetracycline,metronidazole), has been generally used as the optimal second-line therapy. Even after two consecutive failures, several studies have demonstrated that H. pylori eradication can finally be achieved in almost all patients if several "rescue" therapies are consecutively given. It seems that performing culture even after a second eradication failure may not be necessary, as it is possible to construct an overall strategy to maximize H. pylori eradication, based on the different possibilities of empirical treatment (when antibiotic susceptibilities are unknown). Thus, if one does not want to perform culture before the administration of the third treatment after failure of the first two, different empirical treatments exist, including regimens based on: 1, amoxicillin (amoxicillin,PPI at high doses); 2, amoxicillin plus tetracycline (PPI,bismuth,tetracycline,amoxicillin, or ranitidine,bismuth,citrate,tetracyline,amoxicillin); 3, rifabutin (rifabutin,amoxicillin,PPI); 4, levofloxacin (levofloxacin,amoxicillin,PPI); and 5, furazolidone (furazolidone,bismuth,tetracycline,PPI). [source] ,Rescue' Therapy with Rifabutin after Multiple Helicobacter pylori Treatment FailuresHELICOBACTER, Issue 2 2003Javier P. Gisbert abstract Aim. Eradication therapy with proton pump inhibitor, clarithromycin and amoxicillin is extensively used, although it fails in a considerable number of cases. A ,rescue' therapy with a quadruple combination of omeprazole, bismuth, tetracycline and metronidazole (or ranitidine bismuth citrate with these same antibiotics) has been recommended, but it still fails in approximately 20% of cases. Our aim was to evaluate the efficacy and tolerability of a rifabutin-based regimen in patients with two consecutive H. pylori eradication failures. Patients and Methods. Design: Prospective multicenter study. Patients: Consecutive patients in whom a first eradication trial with omeprazole, clarithromycin and amoxicillin and a second trial with omeprazole, bismuth, tetracycline and metronidazole (three patients) or ranitidine bismuth citrate with these same antibiotics (11 patients) had failed were included. Intervention: A third eradication regimen with rifabutin (150 mg bid), amoxicillin (1 g bid) and omeprazole (20 mg bid) was prescribed for 14 days. All drugs were administered together after breakfast and dinner. Compliance with therapy was determined from the interrogatory and the recovery of empty envelopes of medications. Outcome: H. pylori eradication was defined as a negative 13C-urea breath test 8 weeks after completing therapy. Results. Fourteen patients have been included. Mean age ± SD was 42 ± 11 years, 41% males, peptic ulcer (57%), functional dyspepsia (43%). All patients took all the medications and completed the study protocol. Per-protocol and intention-to-treat eradication was achieved in 11/14 patients (79%; 95% confidence interval = 49,95%). Adverse effects were reported in five patients (36%), and included: abdominal pain (three patients), nausea and vomiting (one patient), and oral candidiasis (one patient); no patient abandoned the treatment due to adverse effects. Conclusion. Rifabutin-based rescue therapy constitutes an encouraging strategy after multiple previous eradication failures with key antibiotics such as amoxicillin, clarithromycin, metronidazole and tetracycline. [source] Recent Use of Proton Pump Inhibitor-Based Triple Therapies for the Eradication of H. pylori: A Broad Data ReviewHELICOBACTER, Issue 2 2003Hans-Joachim Ulmer abstract Introduction. For the eradication of Helicobacter pylori a 1-week triple therapy combining proton pump inhibitors with two antibiotics has been recommended as a gold standard therapy. However, a recent broad data review on the efficacy of the different regimens is missing. Therefore, the aim of this study was to systematically review the recent literature. Methods. We undertook a broad data review of the efficacy of nine different 7-day triple therapies consisting of a proton pump inhibitor (lansoprazole, pantoprazole, omeprazole) in its standard dosage and two antibiotics. Relevant original papers on H. pylori eradication in adults, published in English or German between 1995 and 2000, were identified from MEDLINE searches. Studies were reviewed and selected according to predefined criteria. Results. Our predefined criteria were fulfilled by 79 full paper articles including 112 study arms with 8383 patients on intention-to-treat, or 6787 patients on per-protocol basis, respectively. The mean eradication rates unweighted or weighted by the number of patients in the study arm vary from 71.9% to 83.8% for intention-to-treat analysis and from 78.5% to 91.2% for per-protocol analysis. Conclusions. All nine PPI based triple therapy regimens are very effective in H. pylori eradication. The current literature review underlines that the use of either lansoprazole, omeprazole, or pantoprazole combined with two antibiotics yield similar high eradication rates. [source] Is Eradication of Helicobacter pylori With Colloidal Bismuth Subcitrate Quadruple Therapy Safe?HELICOBACTER, Issue 2 2001Rosemary H. Phillips ABSTRACT Background. When standard triple therapy fails to eradicate Helicobacter pylori, quadruple ,rescue' therapy is often used which, in Europe, generally comprises colloidal bismuth subcitrate (CBS) based triple therapy and a proton pump inhibitor. Since hypochlorhydria could greatly increase absorption of the toxic bismuth ion from CBS, we investigated the bismuth status of patients receiving anti- H. pylori quadruple therapy. Materials and Methods. In a prospective open label study 34 patients with nonulcer dyspepsia or peptic ulcer disease, who had failed to eradicate H. pylori with standard triple therapy, were subsequently treated with CBS, omeprazole, amoxycillin and metronidazole (BOAM). A further 35 patients received triple therapy for the eradication of H. pylori: CBS, amoxycillin and metronidazole (BAM) (n = 18); placebo bismuth, amoxycillin and metronidazole (AM) (n = 9); or omeprazole, amoxycillin and metronidazole (OAM) (n = 8). Whole blood bismuth levels were determined before and within 24 hours of completing treatment. Analysis of bismuth was by inductively coupled plasma mass spectrometry, and concentrations were compared between groups and with the Hillemand ,alarm level' for blood bismuth (50,100 µg/l). Results. BOAM gave higher blood bismuth levels than BAM (difference in means 13.1, CI 6.0,20.2, p < .001); three (8.8%) patients taking BOAM had concentrations within the Hillemand alarm level at 54.2, 64.7 and 91.8 µg/l. OAM and AM did not alter baseline blood bismuth levels. Conclusions. Caution should be observed in prescribing CBS with gastric acid suppression, and alternative bismuth preparations should be considered. [source] High Efficacy of Ranitidine Bismuth Citrate, Amoxicillin, Clarithromycin and Metronidazole Twice Daily for Only Five Days in Helicobacter pylori EradicationHELICOBACTER, Issue 2 2001Javier P. Gisbert ABSTRACT Aim. The combination of a proton pump inhibitor (PPI) or ranitidine-bismuth-citrate (Rbc) and two antibiotics for 7,10 days are, at present, the preferred treatments in Helicobacter pylori eradication. However, therapies for fewer than 7 days have been scarcely evaluated and it is unknown whether the length of treatment can be shortened, without a lost of efficacy, if three instead of two antibiotics are used. The aim of our study was to evaluate the efficacy of Rbc plus three antibiotics for only 5 days in H. pylori eradication. Methods. We prospectively studied 80 patients (34% duodenal ulcer, 66% functional dyspepsia) infected by H. pylori. At endoscopy, biopsies were obtained for histological study and rapid urease test, and a 13C-urea breath test was carried out. Urea breath test was repeated 4 weeks after completing eradication treatment with Rbc [400 mg twice a day (bid)], amoxicillin (1 g bid), clarithromycin (500 mg bid) and metronidazole (500 mg bid). All drugs were administered together after breakfast and dinner for 5 days only, and no treatment was administered thereafter. Compliance with therapy was determined from the interrogatory and the recovery of empty envelopes of medications. Results. In 79 out of the 80 patients, H. pylori eradication success or failure was assessed after therapy (one patient was lost from follow-up). All but one of these 79 patients took all the medications (one patient stopped treatment on the day 3 due to nausea/vomiting). Per protocol eradication was achieved in 72/78 (92%; 95% CI, 84,96%) and in 72/80 (90%; 81,95%) by intention-to-treat. Therapy was more effective in patients with duodenal ulcer than in those with functional dyspepsia [100% (87,100%) vs. 85% (73,92%) by intention-to-treat; p < .05]. Adverse effects were described in ten patients (12%), and included the perception of a metallic taste (eight patients), nausea/vomiting (two patients, one of them abandoned the treatment due to this), and diarrhea (two patients). Conclusion. The combination of Rbc, amoxicillin, clarithromycin and metronidazole for only 5 days represents a promising therapy for H. pylori infection, due to its high efficacy, simple posology, low cost and excellent tolerance. [source] Proton pump inhibitor omeprazole use is associated with low bone mineral density in maintenance haemodialysis patientsINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 2 2009A. Kirkpantur Summary Objective:, Limited studies have shown that proton pump inhibitor (PPI) therapy may decrease bone density or insoluble calcium reabsorption through induction of hypochlorhydria. However, PPI therapy may also reduce bone resorption via inhibition of osteoclastic vacuolar proton pumps. The aim of this study was to determine whether the opposing effects of PPI therapy may cause clinically important alterations in bone mineral densitometry (BMD) parameters in maintenance haemodialysis patients. Methods:, Sixty-eight maintenance haemodialysis patients were enrolled in this study. Patients were classified into two groups involving users of PPI therapy (omeprazole 20 mg/day, group 1, n = 36 patients) and non-users of acid suppression drugs (group 2, n = 32 patients). Patients had radius, hip and spine BMD assessed by dual-energy X-ray absorptiometry. Results:, The mean duration of PPI therapy with omeprazole was 27 ± 5 months. The users of PPI therapy had lower values of bone mineral density and T -scores at the anatomical regions than non-users of acid suppression drugs. Serum calcium and phosphate levels, calcium-phosphate product and serum intact parathormone levels and the ratio of users of vitamin D therapy were similar among groups. A mutivariable adjusted odds ratio for lower bone density associated with more than 18 months of omeprazole, when all the potential confounders were considered, was 1.31 in the proximal radius, 0.982 in the femur neck, 0.939 in the trochanter and 1.192 in the lumbal spine. Conclusion:, The present data suggest that PPI therapy should be cautiously prescribed in maintenance haemodialysis patients, especially with lower BMD values. [source] Current practice compared with the international guidelines: endoscopic surveillance of Barrett's esophagusJOURNAL OF EVALUATION IN CLINICAL PRACTICE, Issue 5 2007Nassira Amamra MPH Abstract Rationale, aims and objectives, To describe the current practice for the surveillance of patients with Barrett's esophagus, to compare this practice with the national guidelines published by the French Society of Digestive Endoscopy in 1998 and to identify the factors associated with the compliance to guidelines. Method, To determine the attitudes of French hepatogastroenterologists to screening for Barrett's oesophagus, a postal anonymous questionnaire survey was undertaken. It was sent to 246 hepatogastroenterologists in the Rhone-Alpes area. We defined eight criteria allowed to assess the conformity of practices with the guidelines. We created three topics composed of several criterion. The topics analysed were ,Biopsies', ,Surveillance' and the diagnosis of high grade dysplasia. We studied the factors which could be associated with the compliance with the guidelines. Results, The response rate was 81.3%. For 58.0% of the gastroenterologists, endoscopic biopsy sampling were made according to French guidelines (four-quadrant biopsies at 2 cm intervals). Agreement was 78.0% regarding the interval of surveillance for no dysplasia (every 2 or 3 years) and 78.5% regarding the low-grade dysplasia (every 6 or 12 months). For the management of high-grade dysplasia, 28.6% actually confirm the diagnosis by a second anatomopathologist and 42.0% treated by proton pump inhibitor during 2 months. Concerning the biopsies, the young gastroenterologists and gastroenterologists practising in university hospitals had a better adherence to the guidelines (Relative Risk: 2.22, 95% CI 1.25,3.95 and 3.74, 95% CI 1.04,13.47, respectively). The other factors of risk were not statistically significant. Conclusions, The endoscopic follow-up is mostly realized in accordance with the national guidelines. However, there is a wide variability in individual current practice. [source] Comparison of one-week and two-week empirical trial with a high-dose rabeprazole in non-cardiac chest pain patientsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 9 2009Jeong Hwan Kim Abstract Background:, In patients with non-cardiac chest pain (NCCP), the optimal duration of an empirical trial with a high-dose proton pump inhibitor (PPI) is unclear. We aimed to compare the efficacy of one-week and two-week PPI trial in patients with weekly or more than weekly NCCP and to determine its optimal duration for diagnosing gastroesophageal reflux disease (GERD)-related NCCP. Methods:, Forty-two patients with at least weekly NCCP were enrolled. The baseline symptoms were assessed using a daily symptom diary for seven days. Also, esophago-gastro-duodenoscopy and 24 h esophageal pH monitoring were performed for the diagnosis of GERD. Then, patients were treated with rabeprazole 20 mg twice daily for 14 days. To assess NCCP improvement during the PPI trial, the first week and the second week symptom diary were kept for 1,7 and 8,14 days. The PPI test was considered positive if a symptom score improved (50% compared to the baseline. Results:, There was no significant difference for a positive PPI test between GERD-related NCCP group (n = 8, 50%) and non GERD-related NCCP group (n = 6, 23%) during the first week of the PPI test. However, during the second week, GERD-related NCCP had a higher positive PPI test (n = 13, 81%) than non GERD-related NCCP (n = 7, 27%) (P = 0.001) with a sensitivity and specificity of 81% and 62%, respectively. Conclusions:, The rabeprazole empirical trial was diagnostic for patients with GERD-related NCCP, and its optimal duration was determined to be at least two weeks. [source] Nodular gastritis in adults: Clinical features, endoscopic appearance, histopathological features, and response to therapyJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 6 2008Manisha Dwivedi Abstract Background and Aims:, The present study aims to determine the prevalence of nodular gastritis (NG) and ascertain its clinical presentation and histopathological features in adults. It also assesses its association with Helicobacter pylori and the normalization of endoscopic features, symptoms, and histology after anti H. pylori therapy. Methods:, A total of 7140 patients undergoing upper gastrointestinal endoscopy were studied. Patients showing nodularity of the gastric mucosa at endoscopy and an age- and sex-matched control group with normal gastric mucosa underwent biopsies from the gastric antrum and fundus. The biopsies were assessed for the presence of mucosal inflammation, activity, eosinophils, atrophy, lymphoid follicles, H. pylori, and the presence of intestinal metaplasia. Patients with NG were given triple therapy. Endoscopy and biopsy was repeated after 4 weeks of stopping therapy. The symptoms of the patients and histology were assessed pre- and post-therapy. Results:, Thirty-two patients with an age range of 20,65 years presenting with NG and 40 age- and sex-matched controls were included in the study. Presenting symptoms were epigastric pain (56%), nausea (75%), vomiting (50%) and abdominal bloating (62.5%). All these symptoms regressed significantly after 2 week of triple therapy against H. pylori. A marked improvement in histopathological features was seen post-therapy where the presence of lymphoid aggregates, eosinophils in the mucosa, atrophy, and intestinal metaplasia improved significantly (P < 0.05) after therapy, as compared to the control group of patients. Conclusion:, The symptoms of NG and endoscopic features regress significantly after H. pylori therapy with a proton pump inhibitor and two antibiotics and should routinely be given to treat this form of gastritis. This may prevent progression to further complications. [source] Rabeprazole treatment attenuated Helicobacter pylori -associated gastric mucosal lesion formation in Mongolian gerbilsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 7 2003HIDEKAZU SUZUKI Abstract Background and Aim: Although rabeprazole (RPZ), a proton pump inhibitor, has been reported to have a bactericidal effect on Helicobacter pylori (H. pylori), no studies have been conducted regarding the effect of RPZ on gastric mucosal lesion formation caused by this bacterium. In the present study, we investigated the effect of RPZ on H. pylori -associated gastric mucosal lesion formation. Methods: Sixty-two male Mongolian gerbils were inoculated with H. pylori (ATCC43504) (Hp group) and 60 gerbils with the culture media alone (control group). Some gerbils in the Hp group and in the control group were injected with RPZ (1 mg/kg/day, for 7 days) at the 5th week. Gerbils were evaluated at the 12th, 24th and 48th weeks. Results: In the Hp group, all gerbils were persistently infected for 24 weeks, but 36% became negative for H. pylori at the 48th week. In the Hp + RPZ group, 18% of gerbils at the 12th week, 40% at the 24th week, and 80% at the 48th week, became negative for H. pylori. The level of neutrophil infiltration was significantly decreased in the Hp + RPZ group in comparison to the Hp group, possibly through the effects of RPZ on initial bacterial colonization and resultant inflammation. Even in the gerbils that became H. pylori -negative, the level of neutrophil infiltration was lower in the Hp + RPZ group than in the Hp group. RPZ treatment significantly increased the level of the reduced form of glutathione (GSH) at the 48th week. The elevated levels of the reduced form of GSH may have been reduced by an antioxidation process in the H. pylori -positive Hp + RPZ group. Conclusion: Administration of RPZ not only inhibited gastric H. pylori colonization, but also reduced gastric mucosal inflammation in gerbils, possibly through its antibacterial action as well as pharmacological recruitment of the reduced form of GSH. © 2003 Blackwell Publishing Asia Pty Ltd [source] Anti- Helicobacter pylori therapy in India: Differences in eradication efficiency associated with particular alleles of vacuolating cytotoxin (vacA) geneJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2 2003SUJIT CHAUDHURI Abstract Background and Aims:, The efficiency of Helicobacter pylori eradication varies geographically, as do many parameters that might affect therapeutic efficiency, including bacterial genotype. The aim of the present study was to determine the efficiency of H. pylori eradication using a 10-day proton pump inhibitor-based triple-therapy regimen (omeprazole, clarithromycin and amoxycillin) in an eastern Indian patient population, and to find out the relationship, if any, of the success or failure of the therapy to known features of bacterial genotype. Methods,Helicobacter pylori infections were analyzed in 66 duodenal ulcer patients by upper gastrointestinal endoscopy, rapid urease tests, histology and culture. The cytotoxin-associated gene (cagA) and vacuolating cytotoxin (vacA) gene status of cultured strains were studied by polymerase chain reaction. Treatment was given for 10 days and endoscopy was repeated at 4 and 12 weeks post therapy to monitor ulcer healing and H. pylori eradication. Results:, Ulcer healing was observed in 60 patients (96.77%). Helicobacter pylori was eradicated in 41 (62.12% intention to treat, 66.13% per protocol) of the 66 duodenal ulcer patients, but not in the other 25. The bacteria from 47 patients were genotyped. The only significant disease-associated difference in patterns observed was that the vacA m1 allele was represented more disproportionately among patients with eradication failures (68%) than in those with successful eradication (39%) (P < 0.05) No significant association of vacAs1 (signal sequence allele) or cag pathogenicity island status with persistence was detected. Conclusions:, This study highlights the public health need for cheaper, more cost-effective anti- H. pylori therapies for developing countries, and suggests that subtle features of bacterial genotype can influence therapeutic efficiency. The possibility that particular vacA mid region alleles affect persistence, perhaps through toxin action on particular gastric cell types, merits further study. [source] Acid decomposition of omeprazole in the absence of thiol: A differential pulse polarographic study at the static mercury drop electrode (SMDE)JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 2 2006Ali M. Qaisi Abstract The reactions of omeprazole, a potent proton pump inhibitor (PPI), were investigated in the absence of a nucleophile. Reactions were monitored, using differential pulse polarography (DPP) at the static mercury drop electrode (SMDE), in solutions buffered to pH values ranging from 2.0 to 8.0. The fast, sensitive, and selective electrochemical technique facilitated to repeat recordings of successive voltammograms [peak current (nA) vs. peak potential (volts vs. Ag/AgCl saturated with 3.0 M KCl)]. The DPP signals of omeprazole and its degradation products, believed to be due to sulfur functional group (the principal site of electrode reaction), gave advantages over the previously employed UV detection technique. The latter primarily relied on pyridine and benzimidazole analytical signals, which are common reaction products of PPI in aqueous acidic solutions. After peak identification, the resulting current (nA)-time (s) profiles, demonstrated that omeprazole undergoes degradation to form two main stable compounds, the first is the cyclic sulfenamide (D+), previously believed to be the active inhibitor of the H+, K+ -ATPase, the second is omeprazole dimer. This degradation is highly dependant on pH. Unlike previous studies which reported that the lifetime of D+ is few seconds, the cyclic sulfenamide (D+) was found to be stable for up to 5,20 min. The results further indicated that omeprazole converts into the cyclic sulfenamide in an irreversible reaction, consequently, D+ and sulfenic acid (an intermediate which rapidly converts into D+) were not interconvertable. The present work suggested that the sulfenic acid is the active inhibitor in vivo. In addition, the omeprazole reactions, in the absence of the thiol, were not as complicated as were previously reported. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:384,391, 2006 [source] Stimulatory Effect of N -Methyltyramine, a Congener of Beer, on Pancreatic Secretion in Conscious RatsALCOHOLISM, Issue 2010Eri Tsutsumi Background:, Alcoholic beverages stimulate gastric acid secretion and increase the appetite. Although ingested ethanol stimulates pancreatic secretion, alcoholic beverages contain several congeners. N -methyltyramine (NMT) was isolated from beer as a factor in stimulating gastric acid secretion. In this study, we examined NMT to determine whether the congener stimulated pancreatic secretion in conscious rats. Methods:, Cannulae were inserted into male Wistar rats to separately drain bile and pancreatic secretions: 2 duodenal cannulae, a gastric cannula, and an external jugular vein cannula. The rats were placed in modified Bollman-type restraint cages. After a 4-day recovery period, experiments were conducted on unanesthetized rats. Different concentrations of NMT (5, 25, and 50 ,g/kg) solutions were infused into the stomach. To examine the mechanism, the effects of the proton pump inhibitor, cholecystokinin (CCK-BR) antagonist (YM022), CCK-AR antagonist (CR1505), and atropine were administered prior to the NMT (25 ,g/kg) infusion. The effect of intravenous infusion of NMT (7.5 ,g/kg) was then determined. Moreover, dispersed acini were prepared, and the effect of different concentrations of NMT on amylase release was determined. Results:, Intragastric administration of NMT significantly increased pancreatic exocrine secretion in a dose-dependent manner. Atropine eliminated the stimulatory effect of NMT, but the infusion of the proton pump inhibitor, YM022, and CR1505 did not. Intravenous infusion of NMT did not affect pancreatic secretion, and NMT did not stimulate amylase release in vitro. Conclusions:,N -methyltyramine stimulates pancreatic secretion via the cholinergic gastro-pancreatic reflex. The NMT content in beer was 2 mg/l, so that if a person weighing 60 kg consumes a 750 ml of beer, 25 ,g/kg NMT will be ingested. Therefore, the stimulatory effect of beer on pancreatic secretion was produced not only by ethanol but also by the congener, NMT. [source] The effect of time-of-day dosing on the pharmacokinetics and pharmacodynamics of dexlansoprazole MR: evidence for dosing flexibility with a Dual Delayed Release proton pump inhibitorALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2010R. D. LEE Aliment Pharmacol Ther,31, 1001,1011 Summary Background, Dexlansoprazole MR is a Dual Delayed Release proton pump inhibitor formulated to extend the duration of acid suppression. Aim, To evaluate the pharmacokinetics and pharmacodynamics of dexlansoprazole MR dosed before 4 different meal times. Methods, In this randomized, open-label, four-way crossover study, 48 healthy subjects received dexlansoprazole MR 60 mg once daily 30 min before breakfast, lunch, dinner or an evening snack. Pharmacokinetics of dexlansoprazole MR and intragastric pH were assessed over a 24-h postdose interval on day 5 for each regimen. Results, Absorption was delayed when dexlansoprazole MR was administered before each regimen relative to breakfast; however, systemic exposures of dexlansoprazole at all regimens were bioequivalent. There were no statistically significant differences in mean 24-h intragastric pH between dosing before dinner or an evening snack vs. breakfast; however, there was a small (0.2), but statistically significant difference between lunch and breakfast. There was a statistically significant difference of 7 percentage points in the percentage of time intragastric pH was >4 for the snack regimen relative to the breakfast regimen, but there were no statistically significant differences between lunch or dinner compared with breakfast. Conclusion, Dexlansoprazole MR provides comparable acid control when administered at different times of the day. [source] | |||||||||||||||||||||||||||||||||||||