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Search Results: 1 - 10 of 145434 matches for " Arlene B. Chapman "
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Power to identify a genetic predictor of antihypertensive drug response using different methods to measure blood pressure response
Stephen T Turner, Gary L Schwartz, Arlene B Chapman, Amber L Beitelshees, John G Gums, Rhonda M Cooper-DeHoff, Eric Boerwinkle, Julie A Johnson, Kent R Bailey
Journal of Translational Medicine , 2012, DOI: 10.1186/1479-5876-10-47
Abstract: We analyzed office, home, ambulatory daytime and nighttime BP responses in hypertensive adults randomized to atenolol (N = 242) or hydrochlorothiazide (N = 257) in the Pharmacogenomic Evaluation of Antihypertensive Responses Study. Since different measured BP responses may have different predictors, we tested the "same signal" model by using linear regression methods to determine whether known predictors of BP response depend on the method of BP measurement. We estimated signal-to-noise ratios and compared power to identify a genetic polymorphism predicting BP response measured by each method separately and by weighted averages of multiple methods.After adjustment for pretreatment BP level, known predictors of BP response including plasma renin activity, race, and sex were independent of the method of BP measurement. Signal-to-noise ratios were more than 2-fold greater for home and ambulatory daytime BP responses than for office and ambulatory nighttime BP responses and up to 11-fold greater for weighted averages of all four methods. Power to identify a genetic polymorphism predicting BP response was directly related to the signal-to-noise ratio and, therefore, greatest with the weighted averages.Since different methods of measuring BP response to antihypertensive drug therapy measure the same signal, weighted averages of the BP responses measured by multiple methods minimize measurement error and optimize power to identify genetic predictors of BP response.Although office blood pressure (BP) measurements remain the standard-of-care, averages of out-of-office measurements are more reproducible [1]. Out-of-office averages have also been reported to be more strongly correlated with subclinical target organ damage [2,3] and to better predict future cardiovascular disease events [4-6] than office measurements. Not surprisingly, BP responses to antihypertensive drug therapy are more precisely and accurately determined by out-of-office than office measurements, which are
Pharmacometabolomics Reveals Racial Differences in Response to Atenolol Treatment
William R. Wikoff, Reginald F. Frye, Hongjie Zhu, Yan Gong, Stephen Boyle, Erik Churchill, Rhonda M. Cooper-Dehoff, Amber L. Beitelshees, Arlene B. Chapman, Oliver Fiehn, Julie A. Johnson, Rima Kaddurah-Daouk, Pharmacometabolomics Research Network
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0057639
Abstract: Antihypertensive drugs are among the most commonly prescribed drugs for chronic disease worldwide. The response to antihypertensive drugs varies substantially between individuals and important factors such as race that contribute to this heterogeneity are poorly understood. In this study we use metabolomics, a global biochemical approach to investigate biochemical changes induced by the beta-adrenergic receptor blocker atenolol in Caucasians and African Americans. Plasma from individuals treated with atenolol was collected at baseline (untreated) and after a 9 week treatment period and analyzed using a GC-TOF metabolomics platform. The metabolomic signature of atenolol exposure included saturated (palmitic), monounsaturated (oleic, palmitoleic) and polyunsaturated (arachidonic, linoleic) free fatty acids, which decreased in Caucasians after treatment but were not different in African Americans (p<0.0005, q<0.03). Similarly, the ketone body 3-hydroxybutyrate was significantly decreased in Caucasians by 33% (p<0.0001, q<0.0001) but was unchanged in African Americans. The contribution of genetic variation in genes that encode lipases to the racial differences in atenolol-induced changes in fatty acids was examined. SNP rs9652472 in LIPC was found to be associated with the change in oleic acid in Caucasians (p<0.0005) but not African Americans, whereas the PLA2G4C SNP rs7250148 associated with oleic acid change in African Americans (p<0.0001) but not Caucasians. Together, these data indicate that atenolol-induced changes in the metabolome are dependent on race and genotype. This study represents a first step of a pharmacometabolomic approach to phenotype patients with hypertension and gain mechanistic insights into racial variability in changes that occur with atenolol treatment, which may influence response to the drug.
Impact of Genetic Polymorphisms of SLC2A2, SLC2A5, and KHK on Metabolic Phenotypes in Hypertensive Individuals
MyPhuong T. Le, Maximilian T. Lobmeyer, Marcus Campbell, Jing Cheng, Zhiying Wang, Stephen T. Turner, Arlene B. Chapman, Eric Boerwinkle, John G. Gums, Yan Gong, Richard J. Johnson, Julie A. Johnson
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0052062
Abstract: Objective In the past few decades, consumption of added sugars has increased dramatically. Studies have linked high sugar intake with increased risk for a number of diseases. Importantly, fructose, a component of sugar, has been linked with the development of features of metabolic syndrome. This study determined if single nucleotide polymorphisms in genes involved in fructose transport (solute carrier family 2 facilitated glucose transporter, member 2 (SLC2A2) and solute carrier family 2 facilitated glucose/fructose transporter, member 5 (SLC2A5)) and metabolism (ketohexokinase (KHK)) affect inter-individual variability in metabolic phenotypes, such as increased serum uric acid levels. Materials/Methods The influence of SLC2A2, SLC2A5, and KHK SNPs on metabolic phenotypes was tested in 237 European Americans and 167 African Americans from the Pharmacogenomic Evaluation and Antihypertensive Responses (PEAR) study. Using baseline untreated fasting data, associations were considered significant if p≤0.005. These SNPs were then evaluated for potential replication (p≤0.05) using data from the Genetic Epidemiology of Responses to Antihypertensives (GERA) studies. Results SLC2A5 rs5438 was associated with an increase in serum uric acid in European American males. However, we were unable to replicate the association in GERA. The minor allele of SLC2A2 rs8192675 showed an association with lower high-density lipoproteins in European Americans (A/A: 51.0 mg/dL, A/G: 47.0 mg/dL, G/G: 41.5 mg/dL, p = 0.0034) in PEAR. The association between rs8192675 and lower high-density lipoproteins was replicated in the combined European American GERA study samples (A/A: 47.6 mg/dL, A/G: 48.6 mg/dL, G/G: 41.9 mg/dL, p = 0.0315). Conclusions The association between SLC2A2 rs8192675 and high-density lipoproteins suggests the polymorphism may play a role in influencing high-density lipoproteins and thus metabolic risk of cardiovascular disease.
INTERVENCIóN POR INVITACIóN: Claves de la política exterior colombiana y de sus debilidades principales
Tickner,Arlene B;
Colombia Internacional , 2007,
Abstract: this article develops the thesis that the internationalization of the colombian armed conflict has been carried out using a strategy denominated "intervention by invitation", by which the governments of andrés pastrana and álvaro uribe intensified colombia's association with the united states and requested greater involvement by that country in domestic affairs related to counternarcotics and counterinsurgency. the author discusses a series of conceptual frameworks that allow her to situate this strategy, following which she examines the evolution of colombian foreign policy during the two periods identified.
Colombia frente a la globalización y la inserción internacional: una segunda oportunidad sobre la tierra?.
Arlene B. Tickner.
Colombia Internacional , 1998,
Abstract:
La securitizacion de la crisi colombiana: bases conceptuales y tendencias generales.
Arlene B. Tickner.
Colombia Internacional , 2004,
Abstract: This article argues that perceptions of insecurity and threat produced by Colombia in neighboring countries are not the result of the objective consequences of the regionalization of the Colombian crisis, but rather, depend largely upon internal political dynamics in each country and the ways in which their representatives articulate specific issues as security problems. Following a general conceptual discussion of security and securitization, the author explores the primary practices of securitization that have been employed by Brazil, Colombia, Ecuador, Panama, Peru and Venezuela. This examination allows the article to conclude that the Colombian crisis and U.S. military policy in the region are two factors that currently determine the security dynamics in this zone.
Intervención por invitación Claves de la política exterior colombiana y de sus debilidades principales / Intervention by Invitation Keys to Colombian Foreign Policy and its Main Shortcomings
Arlene B. Tickner
Colombia Internacional , 2007,
Abstract: This article develops the thesis that the internationalization of the Colombian armed conflict has been carried out using a strategy denominated “intervention by invitation”, by which the governments of Andrés Pastrana and álvaro Uribe intensified Colombia’s association with the United States and requested greater involvement by that country in domestic affairs related to counternarcotics and counterinsurgency. The author discusses a series of conceptual frameworks that allow her to situate this strategy, following which she examines the evolution of Colombian foreign policy during the two periods identified.
Editorial
Arlene B. Tickner
Colombia Internacional , 2012,
Abstract:
Hacia un modelo normativo del consenso en las instituciones internacionales.
Arlene B. Tickner.
Colombia Internacional , 1997,
Abstract:
Editorial.
Arlene B.Tickner.
Colombia Internacional , 2002,
Abstract:
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