The Experts below are selected from a list of 321 Experts worldwide ranked by ideXlab platform
James J Kaminski - One of the best experts on this subject based on the ideXlab platform.
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antiulcer agents 6 analysis of the in vitro biochemical and in vivo gastric Antisecretory activity of substituted imidazo 1 2 a pyridines and related analogues using comparative molecular field analysis and hypothetical active site lattice methodolog
Journal of Medicinal Chemistry, 1997Co-Authors: James J Kaminski, Arthur M DoweykoAbstract:A number of substituted imidazo[1,2-a]pyridines and related analogues were selected for analysis of their in vitro biochemical and in vivo gastric Antisecretory activity using comparative molecular field analysis (CoMFA) and hypothetical active site lattice (HASL) methodologies. The training set of compounds selected included those that were also chosen for an extensive molecular modeling study initiated, using the active analog approach, to define the pharmacophore by means of which 1 and its analogues interact with the gastric proton pump enzyme, H+/K(+)-ATPase. Using either CoMFA or HASL, it was possible to identify an optimal alignment paradigm of the proposed bioactive conformation for this series to reasonably predict the in vitro H+/K(+)-ATPase inhibitory potency in the purified enzyme model and the in vivo intravenous gastric Antisecretory activity for compounds outside of the training set. Furthermore, the steric and electrostatic effects suggested by these two independent methods and their influence on determining biological activity were consistent and complementary to each other.
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antiulcer agents 6 analysis of the in vitro biochemical and in vivo gastric Antisecretory activity of substituted imidazo 1 2 a pyridines and related analogues using comparative molecular field analysis and hypothetical active site lattice methodolog
Journal of Medicinal Chemistry, 1997Co-Authors: James J Kaminski, Arthur M DoweykoAbstract:A number of substituted imidazo[1,2-a]pyridines and related analogues were selected for analysis of their in vitro biochemical and in vivo gastric Antisecretory activity using comparative molecular field analysis (CoMFA) and hypothetical active site lattice (HASL) methodologies. The training set of compounds selected included those that were also chosen for an extensive molecular modeling study initiated, using the active analog approach, to define the pharmacophore by means of which 1 and its analogues interact with the gastric proton pump enzyme, H+/K+-ATPase. Using either CoMFA or HASL, it was possible to identify an optimal alignment paradigm of the proposed bioactive conformation for this series to reasonably predict the in vitro H+/K+-ATPase inhibitory potency in the purified enzyme model and the in vivo intravenous gastric Antisecretory activity for compounds outside of the training set. Furthermore, the steric and electrostatic effects suggested by these two independent methods and their influence...
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antiulcer agents 5 inhibition of gastric h k atpase by substituted imidazo 1 2 a pyridines and related analogues and its implication in modeling the high affinity potassium ion binding site of the gastric proton pump enzyme
Journal of Medicinal Chemistry, 1991Co-Authors: James J Kaminski, Bjorn Wallmark, Carin Briving, Britt Marie AnderssonAbstract:: A number of substituted imidazo[1,2-a]pyridines and related analogues were selected for biochemical characterization in vitro against both the purified gastric proton pump enzyme, H+/K(+)-ATPase, and the intact gastric gland. The inhibitory activity in these two in vitro models was then examined for correlation with the gastric Antisecretory potency determined for these compounds in vivo by using the histamine-stimulated Heidenhain pouch dog. Analysis of the biological data suggested that the inhibitory activity of the analogues determined in two in vitro models is predictive of their in vivo gastric Antisecretory activity following intravenous, but not oral, administration. Furthermore, the good correlation observed between the in vitro and in vivo models suggests that these compounds are gastric proton pump inhibitors in vivo. A molecular modeling study of these compounds using the active analogue approach has defined the molecular volume which is shared by the active analogues, as well as the molecular volume which is common to the inactive analogues. Graphical representation of the difference between these molecular volumes can be interpreted in terms of a hypothetical description of the pharmacophore by means of which 3-(cyanomethyl)-2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine, Sch 28080 (1) and its analogues interact with the gastric proton pump enzyme, H+/K(+)-ATPase.
Arthur M Doweyko - One of the best experts on this subject based on the ideXlab platform.
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antiulcer agents 6 analysis of the in vitro biochemical and in vivo gastric Antisecretory activity of substituted imidazo 1 2 a pyridines and related analogues using comparative molecular field analysis and hypothetical active site lattice methodolog
Journal of Medicinal Chemistry, 1997Co-Authors: James J Kaminski, Arthur M DoweykoAbstract:A number of substituted imidazo[1,2-a]pyridines and related analogues were selected for analysis of their in vitro biochemical and in vivo gastric Antisecretory activity using comparative molecular field analysis (CoMFA) and hypothetical active site lattice (HASL) methodologies. The training set of compounds selected included those that were also chosen for an extensive molecular modeling study initiated, using the active analog approach, to define the pharmacophore by means of which 1 and its analogues interact with the gastric proton pump enzyme, H+/K(+)-ATPase. Using either CoMFA or HASL, it was possible to identify an optimal alignment paradigm of the proposed bioactive conformation for this series to reasonably predict the in vitro H+/K(+)-ATPase inhibitory potency in the purified enzyme model and the in vivo intravenous gastric Antisecretory activity for compounds outside of the training set. Furthermore, the steric and electrostatic effects suggested by these two independent methods and their influence on determining biological activity were consistent and complementary to each other.
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antiulcer agents 6 analysis of the in vitro biochemical and in vivo gastric Antisecretory activity of substituted imidazo 1 2 a pyridines and related analogues using comparative molecular field analysis and hypothetical active site lattice methodolog
Journal of Medicinal Chemistry, 1997Co-Authors: James J Kaminski, Arthur M DoweykoAbstract:A number of substituted imidazo[1,2-a]pyridines and related analogues were selected for analysis of their in vitro biochemical and in vivo gastric Antisecretory activity using comparative molecular field analysis (CoMFA) and hypothetical active site lattice (HASL) methodologies. The training set of compounds selected included those that were also chosen for an extensive molecular modeling study initiated, using the active analog approach, to define the pharmacophore by means of which 1 and its analogues interact with the gastric proton pump enzyme, H+/K+-ATPase. Using either CoMFA or HASL, it was possible to identify an optimal alignment paradigm of the proposed bioactive conformation for this series to reasonably predict the in vitro H+/K+-ATPase inhibitory potency in the purified enzyme model and the in vivo intravenous gastric Antisecretory activity for compounds outside of the training set. Furthermore, the steric and electrostatic effects suggested by these two independent methods and their influence...
Robert T Jensen - One of the best experts on this subject based on the ideXlab platform.
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prospective study of the need for long term Antisecretory therapy in patients with zollinger ellison syndrome following successful curative gastrinoma resection
Alimentary Pharmacology & Therapeutics, 2007Co-Authors: David C Metz, Richard V Benya, Vitaly A Fishbeyn, Joseph R Pisegna, Murray Orbuch, Doris B Strader, Jeffrey A Norton, Robert T JensenAbstract:SUMMARY A long-term cure is now possible in more than 30% of selected patients with Zollinger–Ellison syndrome who undergo gastrinoma resection. The need, however, for continued gastric acid Antisecretory therapy in these patients remains controversial. The current study was designed to determine whether post-operative Antisecretory therapy is needed in patients who have undergone successful gastrinoma resection and, if so, to attempt to define criteria with which to identify patients who require therapy. Twenty-eight consecutive patients who had previously undergone curative gastrinoma resection were prospectively studied. When Antisecretory therapy was discontinued, 43% (12/28) of these patients developed gastro-oesophageal reflux, diarrhoea, acid–peptic symptoms or endoscopic evidence of acid-peptic disease within 2 weeks and were deemed to have failed a trial of Antisecretory drug withdrawal. The remaining 57% (16/28) of patients who successfully discontinued Antisecretory therapy were followed for a mean time of 31 months after withdrawal of therapy. Analysis of acid output studies pre-operatively, as well as at the time of drug withdrawal, demonstrated that patients who were unable to discontinue Antisecretory therapy exhibited higher pre-operative maximal acid output values and higher basal acid output values at the time of attempted drug withdrawal than patients who were able to discontinue therapy. Despite these findings, there was significant overlap in acid output values between groups so that it was not possible to define specific acid output criteria for successful drug withdrawal. Pre-operative clinical characteristics, such as the presence or absence of gastro-esophageal reflux or acid-peptic disease, or post-operative laboratory values, such as the fasting serum gastrin level, did not correlate with the ability to discontinue Antisecretory therapy. We conclude that following successful curative gastrinoma resection, 40% of patients still require Antisecretory therapy and that both symptom evaluation as well as upper endoscopy should be used to guide attempted drug withdrawal. Although patients who are not able to discontinue therapy have significantly higher acid output measurements than those who are able to discontinue therapy, neither acid output criteria nor any other laboratory or clinical characteristics are able to predict the need for continued Antisecretory therapy in these patients.
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iron absorption in patients with zollinger ellison syndrome treated with long term gastric acid Antisecretory therapy
Alimentary Pharmacology & Therapeutics, 1998Co-Authors: C A Stewart, B Termanini, V E Sutliff, Jose Serrano, Fathia Gibril, Robert T JensenAbstract:Background: Gastric acid secretion is important for absorption of dietary non-haem iron, and iron deficiency is common in gastric hyposecretory states such as after gastric resection. It is not known if prolonged, continuous treatment with potent acid suppressants such as omeprazole will lead to iron deficiency or lower body iron stores. Aim: To assess iron stores and the occurrence of iron deficiency anaemia in patients with Zollinger–Ellison syndrome (ZES) treated long-term with gastric Antisecretory drugs. Methods: One hundred and nine patients with ZES but without previous gastric resections were studied. All patients underwent assessment of acid control on Antisecretory agents, determination of tumour extent, evaluation of haematological parameters (Hct, haemoglobin, WBC, MCV, MCHC), and determination of serum iron parameters (iron, ferritin, transferrin, iron/transferrin ratio). Acid control values for the last 4 years were reviewed, the presence or absence of acid hyposecretion determined using three different criteria and this result correlated with haematological and iron parameters. Results: Eighty-nine patients were taking omeprazole, nine patients were taking histamine H2-antagonists and 11 patients were taking no drugs following curative resection. The mean duration of omeprazole treatment was 5.7 years (range 0.7–12.5 years) and total duration of any treatment was 10.1 years (range 0.7–21 years). Acid hyposecretion was present by at least one criterion in 45% of patients. There were no significant differences between patients with or without acid hyposecretion, taking or not taking omeprazole, having different durations of omeprazole treatment or different durations of total time receiving any Antisecretory treatment, for any serum iron parameter, haematological parameter, or for the frequency of iron deficiency. Males and females did not differ in percentage with low ferritin levels or percentage with iron deficiency. Conclusions: Continuous treatment with omeprazole for 6 years or continuous treatment with any gastric Antisecretory drug for 10 years does not cause decreased body iron stores or iron deficiency. These results suggest that, in contrast to recent results which show yearly monitoring of vitamin B12 in such patients is needed, such monitoring for iron parameters is not necessary.
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control of gastric acid hypersecretion in the management of patients with zollinger ellison syndrome
World Journal of Surgery, 1993Co-Authors: David C Metz, Richard V Benya, Vitaly A Fishbeyn, Joseph R Pisegna, Robert T JensenAbstract:During the last 5 years important advances have occurred in the control of gastric acid hypersecretion in Zollinger-Ellison syndrome (ZES). The increased availability of potent gastric acid Antisecretory agents such as histamine H2-receptor antagonists and more recently the H+K+-ATPase inhibitors such as omeprazole and lansoprazole have made it possible to medically control acid secretion in all patients. Increased understanding of the variation in Antisecretory drug dosage between individual patients has led to identification of criteria to ensure effective Antisecretory control and to the recognition of subgroups of patients who require special monitoring. Effective regimens for parenteral Antisecretory control during surgery have been established. The importance of parathyroidectomy in patients with multiple endocrine neoplasia type I with ZES and the possible usefulness of highly selective vagotomy have been investigated. We review here the new data that led to increased understanding in each of these areas from our studies and studies by others.
Enrique Dominguezmunoz - One of the best experts on this subject based on the ideXlab platform.
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helicobacter pylori eradication therapy vs Antisecretory non eradication therapy with or without long term maintenance Antisecretory therapy for the prevention of recurrent bleeding from peptic ulcer
Cochrane Database of Systematic Reviews, 2004Co-Authors: Javier P Gisbert, Sam Khorrami, Fernando Carballo, Xavier Calvet, Emili Gene, Enrique DominguezmunozAbstract:Background Peptic ulcer is the main cause for upper gastrointestinal haemorrhage, and Helicobacter pylori (H.pylori) infection is the main etiologic factor for peptic ulcer disease. Maintenance Antisecretory therapy is the standard long-term treatment for patients with bleeding ulcers to prevent recurrent bleeding. The efficacy of H. pylori eradication for the prevention of rebleeding from peptic ulcer is unknown. Objectives To compare the efficacy of H. pylori eradication therapy vs. Antisecretory non-eradication therapy (with or without long-term maintenance Antisecretory therapy) for the prevention of recurrent bleeding from peptic ulcer. Search methods We searched the Cochrane Controlled Trials Register (the Cochrane Library issue 4, 2003), MEDLINE (January 1966 to January 2004), EMBASE (January 1988 to January 2004), CINAHL (January 1982 to January 2004), and reference lists of articles. We also conducted a manual search from several congresses. The search strategy was re-run in January 2005 and October 2008, but no new trials were found. Selection criteria Controlled clinical trials comparing the efficacy of H. pylori eradication therapy vs. Antisecretory non-eradication therapy (with or without long-term maintenance Antisecretory therapy) for the prevention of recurrent bleeding from peptic ulcer. Data collection and analysis Data extraction and quality assessment of studies was done by two reviewers. Study authors were contacted for additional information. Main results Seven studies with a total of 578 patients were included in the first comparison: mean percentage of rebleeding in H. pylori eradication therapy group was 2.9%, and in the non-eradication therapy group without subsequent long-term maintenance Antisecretory therapy it was 20% (OR 0.17, 95% CI 0.10 to 0.32; there was no statistical evidence of heterogeneity; NNT was 7, 95% CI 5 to 11). Three studies with a total of 470 patients were included in the second comparison: mean percentage of rebleeding in H. pylori eradication therapy group was 1.6%, and in non-eradication therapy group with long-term maintenance Antisecretory therapy it was 5.6% (OR 0.24, 95% CI 0.09 to 0.67; heterogeneity was not demonstrated; NNT was 20, 95% CI 12 to 100). Subgroup analyses were carried out to examine the effect of NSAIDS and of excluding H.pylori eradication failures from the analyses. Authors' conclusions Treatment of H. pylori infection is more effective than Antisecretory non-eradication therapy (with or without long-term maintenance Antisecretory therapy) in preventing recurrent bleeding from peptic ulcer. All patients with peptic ulcer bleeding should be tested for H. pylori infection, and eradication therapy should be prescribed to H. pylori-positive patients.
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meta analysis helicobacter pylori eradication therapy vs Antisecretory non eradication therapy for the prevention of recurrent bleeding from peptic ulcer
Alimentary Pharmacology & Therapeutics, 2004Co-Authors: Javier P Gisbert, Sam Khorrami, Fernando Carballo, Xavier Calvet, Emili Gene, Enrique DominguezmunozAbstract:Summary Aim : To perform a meta-analysis comparing the efficacy of Helicobacter pylori eradication therapy vs. Antisecretory non-eradication therapy for the prevention of recurrent bleeding from peptic ulcer. Methods : A search was made of the Cochrane Controlled Trials Register, MEDLINE, EMBASE, CINAHL and several congresses for controlled clinical trials comparing the efficacy of H. pylori eradication therapy vs. Antisecretory non-eradication therapy for the prevention of peptic ulcer re-bleeding. Studies with all patients taking non-steroidal anti-inflammatory drugs were excluded. Extraction and quality assessment of the studies were performed by two reviewers. Results : In the first meta-analysis, the mean percentage of re-bleeding in the H. pylori eradication therapy group was 4.5%, compared with 23.7% in the non-eradication therapy group without long-term Antisecretory therapy [odds ratio, 0.18; 95% confidence interval (CI), 0.09–0.37; ‘number needed to treat’ (NNT), 5; 95% CI, 4–8]. In the second meta-analysis, the re-bleeding rate in the H. pylori eradication therapy group was 1.6%, compared with 5.6% in the non-eradication therapy group with maintenance Antisecretory therapy (odds ratio, 0.25; 95% CI, 0.08–0.76; NNT, 20; 95% CI, 12–100). When only patients with successful H. pylori eradication were included, the re-bleeding rate was 1%. Conclusions : The treatment of H. pylori infection is more effective than Antisecretory non-eradication therapy (with or without long-term maintenance Antisecretory treatment) in the prevention of recurrent bleeding from peptic ulcer. Consequently, all patients with peptic ulcer bleeding should be tested for H. pylori, and eradication therapy should be prescribed to infected patients.
Javier P Gisbert - One of the best experts on this subject based on the ideXlab platform.
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helicobacter pylori eradication therapy vs Antisecretory non eradication therapy with or without long term maintenance Antisecretory therapy for the prevention of recurrent bleeding from peptic ulcer
Cochrane Database of Systematic Reviews, 2004Co-Authors: Javier P Gisbert, Sam Khorrami, Fernando Carballo, Xavier Calvet, Emili Gene, Enrique DominguezmunozAbstract:Background Peptic ulcer is the main cause for upper gastrointestinal haemorrhage, and Helicobacter pylori (H.pylori) infection is the main etiologic factor for peptic ulcer disease. Maintenance Antisecretory therapy is the standard long-term treatment for patients with bleeding ulcers to prevent recurrent bleeding. The efficacy of H. pylori eradication for the prevention of rebleeding from peptic ulcer is unknown. Objectives To compare the efficacy of H. pylori eradication therapy vs. Antisecretory non-eradication therapy (with or without long-term maintenance Antisecretory therapy) for the prevention of recurrent bleeding from peptic ulcer. Search methods We searched the Cochrane Controlled Trials Register (the Cochrane Library issue 4, 2003), MEDLINE (January 1966 to January 2004), EMBASE (January 1988 to January 2004), CINAHL (January 1982 to January 2004), and reference lists of articles. We also conducted a manual search from several congresses. The search strategy was re-run in January 2005 and October 2008, but no new trials were found. Selection criteria Controlled clinical trials comparing the efficacy of H. pylori eradication therapy vs. Antisecretory non-eradication therapy (with or without long-term maintenance Antisecretory therapy) for the prevention of recurrent bleeding from peptic ulcer. Data collection and analysis Data extraction and quality assessment of studies was done by two reviewers. Study authors were contacted for additional information. Main results Seven studies with a total of 578 patients were included in the first comparison: mean percentage of rebleeding in H. pylori eradication therapy group was 2.9%, and in the non-eradication therapy group without subsequent long-term maintenance Antisecretory therapy it was 20% (OR 0.17, 95% CI 0.10 to 0.32; there was no statistical evidence of heterogeneity; NNT was 7, 95% CI 5 to 11). Three studies with a total of 470 patients were included in the second comparison: mean percentage of rebleeding in H. pylori eradication therapy group was 1.6%, and in non-eradication therapy group with long-term maintenance Antisecretory therapy it was 5.6% (OR 0.24, 95% CI 0.09 to 0.67; heterogeneity was not demonstrated; NNT was 20, 95% CI 12 to 100). Subgroup analyses were carried out to examine the effect of NSAIDS and of excluding H.pylori eradication failures from the analyses. Authors' conclusions Treatment of H. pylori infection is more effective than Antisecretory non-eradication therapy (with or without long-term maintenance Antisecretory therapy) in preventing recurrent bleeding from peptic ulcer. All patients with peptic ulcer bleeding should be tested for H. pylori infection, and eradication therapy should be prescribed to H. pylori-positive patients.
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meta analysis helicobacter pylori eradication therapy vs Antisecretory non eradication therapy for the prevention of recurrent bleeding from peptic ulcer
Alimentary Pharmacology & Therapeutics, 2004Co-Authors: Javier P Gisbert, Sam Khorrami, Fernando Carballo, Xavier Calvet, Emili Gene, Enrique DominguezmunozAbstract:Summary Aim : To perform a meta-analysis comparing the efficacy of Helicobacter pylori eradication therapy vs. Antisecretory non-eradication therapy for the prevention of recurrent bleeding from peptic ulcer. Methods : A search was made of the Cochrane Controlled Trials Register, MEDLINE, EMBASE, CINAHL and several congresses for controlled clinical trials comparing the efficacy of H. pylori eradication therapy vs. Antisecretory non-eradication therapy for the prevention of peptic ulcer re-bleeding. Studies with all patients taking non-steroidal anti-inflammatory drugs were excluded. Extraction and quality assessment of the studies were performed by two reviewers. Results : In the first meta-analysis, the mean percentage of re-bleeding in the H. pylori eradication therapy group was 4.5%, compared with 23.7% in the non-eradication therapy group without long-term Antisecretory therapy [odds ratio, 0.18; 95% confidence interval (CI), 0.09–0.37; ‘number needed to treat’ (NNT), 5; 95% CI, 4–8]. In the second meta-analysis, the re-bleeding rate in the H. pylori eradication therapy group was 1.6%, compared with 5.6% in the non-eradication therapy group with maintenance Antisecretory therapy (odds ratio, 0.25; 95% CI, 0.08–0.76; NNT, 20; 95% CI, 12–100). When only patients with successful H. pylori eradication were included, the re-bleeding rate was 1%. Conclusions : The treatment of H. pylori infection is more effective than Antisecretory non-eradication therapy (with or without long-term maintenance Antisecretory treatment) in the prevention of recurrent bleeding from peptic ulcer. Consequently, all patients with peptic ulcer bleeding should be tested for H. pylori, and eradication therapy should be prescribed to infected patients.