George alen Veterans Affairs Medical Center

Salt Lake City, UT, United States

George alen Veterans Affairs Medical Center

Salt Lake City, UT, United States

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Hernandez-Vivanco A.,Autonomous University of Madrid | Hone A.J.,Autonomous University of Madrid | Scadden M.,University of Utah | Carmona-Hidalgo B.,Autonomous University of Madrid | And 3 more authors.
PLoS ONE | Year: 2014

Nicotinic acetylcholine receptors (nAChRs) that contain α6 and β4 subunits have been demonstrated functionally in human adrenal chromaffin cells, rat dorsal root ganglion neurons, and on noradrenergic terminals in the hippocampus of adolescent mice. In human adrenal chromaffin cells, α6β4* nAChRs (the asterisk denotes the possible presence of additional subunits) are the predominant subtype whereas in rodents, the predominant nAChR is the α3β4* subtype. Here we present molecular and pharmacological evidence that chromaffin cells from monkey (Macaca mulatta) also express α6β4* receptors. PCR was used to show the presence of transcripts for α6 and β4 subunits and pharmacological characterization was performed using patch-clamp electrophysiology in combination with α-conotoxins that target the α6β4* subtype. Acetylcholine-evoked currents were sensitive to inhibition by BuIA[T5A,P6O] and MII[H9A,L15A]; α-conotoxins that inhibit α6-containing nAChRs. Two additional agonists were used to probe for the expression of α7 and β2-containing nAChRs. Cells with currents evoked by acetylcholine were relatively unresponsive to the α7-selctive agonist choline but responded to the agonist 5-I-A-85380. These studies provide further insights into the properties of natively expressed α6β4* nAChRs. © 2014 Hernandez-Vivanco et al.


Hone A.J.,Autonomous University of Madrid | McIntosh J.M.,University of Utah | McIntosh J.M.,George alen Veterans Affairs Medical Center | Azam L.,University of Utah | And 6 more authors.
Molecular Pharmacology | Year: 2015

Ligands that selectively inhibit human α3β2 and α6β2 nicotinic acetylcholine receptor (nAChRs) and not the closely related α3β4 and α6β4 subtypes are lacking. Current α-conotoxins (α-Ctxs) that discriminate among these nAChR subtypes in rat fail to discriminate among the human receptor homologs. In this study, we describe the development of α-Ctx LvIA(N9R,V10A) that is 3000-fold more potent on oocyte-expressed human α3b2 than α3b4 and 165-fold more potent on human a6/a3β2β3 than a6/ a3β4 nAChRs. This analog was used in conjuction with three other α-Ctx analogs and patch-clamp electrophysiology to characterize the nAChR subtypes expressed by human adrenal chromaffin cells. LvIA(N9R,V10A) showed little effect on the acetylcholine-evoked currents in these cells at concentrations expected to inhibit nAChRs with β2 ligand-binding sites. In contrast, the b4-selective α-Ctx BuIA(T5A,P6O) inhibited .98% of the acetylcholine-evoked current, indicating that most of the heteromeric receptors contained b4 ligand-binding sites. Additional studies using the α6-selective α-Ctx PeIA(A7V,S9H,V10A, N11R,E14A) indicated that the predominant heteromeric nAChR expressed by human adrenal chromaffin cells is the a3b4∗ subtype (asterisk indicates the possible presence of additional subunits). This conclusion was supported by polymerase chain reaction experiments of human adrenal medulla gland and of cultured human adrenal chromaffin cells that demonstrated prominent expression of RNAs for α3, α5, α7, β2, and β4 subunits and a low abundance of RNAs for α2, α4, α6, and α10 subunits. © 2015 by The American Society for Pharmacology and Experimental Therapeutics.


Hayman M.A.,Geriatric Research Education and Clinical Center | Hayman M.A.,University of Utah | Nativi J.N.,George alen Veterans Affairs Medical Center | Stehlik J.,George alen Veterans Affairs Medical Center | And 10 more authors.
American Journal of Physiology - Heart and Circulatory Physiology | Year: 2010

To better characterize the contribution of both central and peripheral mechanisms to passive limb movement-induced hyperemia, we studied nine recent (<2 yr) heart transplant (HTx) recipients (56 ± 4 yr) and nine healthy controls (58 ± 5 yr). Measurements of heart rate (HR), stroke volume (SV), cardiac output (CO), and femoral artery blood flow were recorded during passive knee extension. Peripheral vascular function was assessed using brachial artery flow-mediated dilation (FMD). During passive limb movement, the HTx recipients lacked an HR response (0 ± 0 beats/min, Δ0%) but displayed a significant increase in CO (0.4 ± 0.1 l/min, Δ5%) although attenuated compared with controls (1.0 ± 0.2 l/min, Δ18%). Therefore, the rise in CO in the HTx recipients was solely dependent on increased SV (5 ± 1 ml, Δ5%) in contrast with the controls who displayed significant increases in both HR (6 ± 2 beats/min, Δ11%) and SV (5 ± 2 ml, Δ7%). The transient increase in femoral blood volume entering the leg during the first 40 s of passive movement was attenuated in the HTx recipients (24 ± 8 ml) compared with controls (93 ± 7 ml), whereas peripheral vascular function (FMD) appeared similar between HTx recipients (8 ± 2%) and controls (6 ± 1%). These data reveal that the absence of an HR increase in HTx recipients significantly impacts the peripheral vascular response to passive movement in this population and supports the concept that an increase in CO is a major contributor to exercise-induced hyperemia.


Buchmann L.,University of Utah | Buchmann L.,Huntsman Cancer Institute | Buchmann L.,George alen Veterans Affairs Medical Center | Ashby S.,University of Utah | And 4 more authors.
Otolaryngology - Head and Neck Surgery (United States) | Year: 2015

Objective. The purpose of this study is to evaluate levels of psychosocial distress in thyroid cancer patients. An analysis of factors contributing to levels of distress is included. Study Design. Individual retrospective cohort study. Setting. Head and neck cancer clinic at the Huntsman Cancer Institute. Subjects and Methods. A total of 118 newly diagnosed thyroid cancer patients were included in the study. Univariate and multivariate analyses evaluated levels of and factors contributing to distress. Results. Almost half (43.3%) of patients had significant distress. Those with self-reported psychiatric history, use of antidepressant medication, and history of radiation treatment had higher levels of distress. On multivariate analysis, patient endorsement of emotional issues predicted a higher distress level. Conclusions. Thyroid cancer patients have high distress levels. Identification of thyroid cancer patients with high distress levels is important to offer additional support during cancer therapy © American Academy of Otolaryngology-Head and Neck Surgery Foundation 2015.


Copeland C.T.,The University of Oklahoma Health Sciences Center | Mahoney J.J.,The University of Oklahoma Health Sciences Center | Block C.K.,The University of Oklahoma Health Sciences Center | Linck J.F.,Veterans Affairs Medical Center | And 4 more authors.
Archives of Clinical Neuropsychology | Year: 2016

This investigation adds to the burgeoning body of research concerned with discriminating performance and symptom validity tests (SVTs) through examination of their differential relationships with cognitive performance and symptom self-report measures. To the authors' current knowledge, prior studies have not assessed differences between participants who fail either a performance validity test (PVT) or an SVT but not both. As part of their neuropsychological evaluations at four Veterans Affairs medical centers across the United States, participants were administered a fixed, standardized battery that consisted of performance validity, symptom validity, cognitive performance, and symptom self-report measures. Compared with participants who failed a PVT and an SVT, participants who passed both and participants who only passed a PVT demonstrated better cognitive performance and self-reported fewer symptoms. Results support differential clinical utility of performance validity and SVTs when assessing cognitive performance and symptom self-report. © 2015 The Author.


Madaras-Kelly K.,Veterans Affairs Medical Center | Madaras-Kelly K.,Idaho State University | Jones M.,George alen Veterans Affairs Medical Center | Remington R.,Veterans Affairs Medical Center | And 4 more authors.
Infection Control and Hospital Epidemiology | Year: 2014

objective. Development of a numerical score to measure the microbial spectrum of antibiotic regimens (spectrum score) and method to identify antibiotic de-escalation events based on application of the score. design. Web-based modified Delphi method. participants. Physician and pharmacist antimicrobial stewards practicing in the United States recruited through infectious diseases- focused listservs. methods. Three Delphi rounds investigated: organisms and antibiotics to include in the spectrum score, operationalization of rules for the score, and de-escalation measurement. A 4-point ordinal scale was used to score antibiotic susceptibility for organism-antibiotic domain pairs. Antibiotic regimen scores, which represented combined activity of antibiotics in a regimen across all organism domains, were used to compare antibiotic spectrum administered early (day 2) and later (day 4) in therapy. Changes in spectrum score were calculated and compared with Delphi participants' judgments on de-escalation with 20 antibiotic regimen vignettes and with non-Delphi steward judgments on de-escalation of 300 pneumonia regimen vignettes. Method sensitivity and specificity to predict expert de-escalation status were calculated. results. Twenty-four participants completed all Delphi rounds. Expert support for concepts utilized in metric development was identified. For vignettes presented in the Delphi, the sign of change in score correctly classified de-escalation in all vignettes except those involving substitution of oral antibiotics. The sensitivity and specificity of the method to identify de-escalation events as judged by non-Delphi stewards were 86.3% and 96.0%, respectively. conclusions. Identification of de-escalation events based on an algorithm that measures microbial spectrum of antibiotic regimens generally agreed with steward judgments of de-escalation status. © 2014 by The Society for Healthcare Epidemiology of America. All rights reserved.


PubMed | Michael bakey Veterans Affairs Medical Center, The University of Oklahoma Health Sciences Center, Minneapolis Veterans Affairs Health Care System, Veterans Affairs Medical Center and George alen Veterans Affairs Medical Center
Type: Journal Article | Journal: Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists | Year: 2016

This investigation adds to the burgeoning body of research concerned with discriminating performance and symptom validity tests (SVTs) through examination of their differential relationships with cognitive performance and symptom self-report measures. To the authors current knowledge, prior studies have not assessed differences between participants who fail either a performance validity test (PVT) or an SVT but not both. As part of their neuropsychological evaluations at four Veterans Affairs medical centers across the United States, participants were administered a fixed, standardized battery that consisted of performance validity, symptom validity, cognitive performance, and symptom self-report measures. Compared with participants who failed a PVT and an SVT, participants who passed both and participants who only passed a PVT demonstrated better cognitive performance and self-reported fewer symptoms. Results support differential clinical utility of performance validity and SVTs when assessing cognitive performance and symptom self-report.


Madaras-Kelly K.,Boise Veterans Affairs Medical Center | Madaras-Kelly K.,Idaho State University | Jones M.,George alen Veterans Affairs Medical Center | Jones M.,University of Utah | And 9 more authors.
Journal of Antimicrobial Chemotherapy | Year: 2016

Objectives: The objective of this study was to measure quantitatively antimicrobial de-escalation utilizing electronic medication administration data based on the spectrum of activity for antimicrobial therapy (i.e. spectrum score) to identify variables associated with de-escalation in a nationwide healthcare system. Methods: A retrospective cohort study of patients hospitalized for healthcare-associated pneumonia was conducted in Veterans Affairs Medical Centers (n = 119). Patients hospitalized for healthcare-associated pneumonia on acute-care wards between 5 and 14 days who received antimicrobials for ≤3 days during calendar years 2008-11 were evaluated. The spectrum score method was applied at the patient level to measure de-escalation on day 4 of hospitalization. De-escalation was expressed in aggregate and facility-level proportions. Logistic regression was used to assess variables associated with de-escalation. ORs with 95% CIs were reported. Results: Among 9319 patients, the de-escalation proportion was 28.3% (95% CI 27.4-29.2), which varied 6-fold across facilities [median (IQR) facility-level de-escalation proportion 29.1% (95% CI 21.7-35.6)]. Variables associated with de-escalation included initial broad-spectrum therapy (OR 1.5, 95% CI 1.4-1.5 for each 10% increase in spectrum), collection of respiratory tract cultures (OR 1.1, 95% CI 1.0-1.2) and care in higher complexity facilities (OR 1.3, 95% CI 1.1-1.6). Respiratory tract cultures were collected from 35.3% (95% CI 32.7-37.7) of patients. Conclusions: De-escalation of antimicrobial therapy was limited and varied substantially across facilities. De-escalation was associated with respiratory tract culture collection and treatment in a high complexity-level facility. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.


PubMed | Winston-Salem State University, UNC Greensboro and George alen Veterans Affairs Medical Center
Type: Journal Article | Journal: International journal of sports medicine | Year: 2014

African-Americans are at a significantly greater risk for developing several diseases and conditions. These conditions often have underlying oxidative stress mechanisms. Therefore the purpose of this investigation was to ascertain the post-exercise oxidative response to a single bout of aerobic exercise in African-American and Caucasian college-age females. A total of 10 African-American and 10 Caucasian females completed the study. Each subject had her VO2 max measured while exercising on a treadmill. A week later, each subject returned to the laboratory and performed a 30-min run at 70% of her VO2max. Blood samples were taken immediately prior to and following exercise for analysis. Lipid hydroperoxides, protein carbonyls, malondialdehyde, xanthine oxidase, glutathione in the reduced (GSH) and oxidized (GSSG) forms, TNF and interleukin 6 were measured from blood taken before and after exercise. Significance was set at p0.05 a priori. Xanthine oxidase was the only measure that did not significantly increase following exercise. All other markers showed a significant elevation in response to the exercise bout with no difference between groups except that the Caucasian group had significantly higher malondialdehyde post-exercise compared to the African-American group. This cohort of college-age African-American and Caucasian females showed little difference in their response to a single 30-min run at 70% of their max in the markers of oxidative stress within the blood.

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