20 results on '"Elaine Yang"'
Search Results
2. The Use of Critical Care Services After Orthopedic Surgery at a High-Volume Orthopedic Medical Center: A Retrospective Study
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Jashvant Poeran, Elaine Yang, Danya DeMeo, Kethy M. Jules-Elysee, Jemiel A Nejim, Lauren A. Wilson, Haoyan Zhong, Jiabin Liu, Genewoo Hong, Stavros G. Memtsoudis, Meghan A. Kirksey, and Sean Garvin
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medicine.medical_specialty ,business.industry ,General surgery ,Retrospective cohort study ,Intensive care unit ,law.invention ,law ,Orthopedic surgery ,medicine ,Orthopedics and Sports Medicine ,Surgery ,Center (algebra and category theory) ,In patient ,business ,Volume (compression) - Abstract
Background: With an aging population, orthopedics has become one of the largest and fastest growing surgical fields. However, data on the use of critical care services (CCS) in patients undergoing orthopedic procedures remain sparse. Purpose: We sought to elucidate the prevalence and characteristics of patients requiring CCS and intermediate levels of care after orthopedic surgeries at a high-volume orthopedic medical center. Methods: We retrospectively reviewed inpatient electronic medical record data (2016–2020) at a high-volume orthopedic hospital. Patients who required CCS and intermediate levels of care, including step-down unit (SDU) and telemetry services, were identified. We described characteristics related to patients, procedures, and outcomes, including type of advanced services required and surgery type. Results: Of the 50,387 patients who underwent orthopedic inpatient surgery, 1.6% required CCS and 21.6% were admitted to an SDU. Additionally, 482 (1.0%) patients required postoperative mechanical ventilation and 3602 (7.1%) patients required continuous positive airway pressure therapy. Spine surgery patients were the most likely to require any form of advanced care (45.7%). Conclusions: This retrospective review found that approximately one-fourth of orthopedic surgery patients were admitted to units that provided critical and intermediate levels of care. These results may prove useful to hospitals in estimating needs and allocating resources for advanced and critical care services after orthopedic surgery.
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- 2021
3. The propofol binding sites of prokaryotic voltage-gated sodium channels
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Kellie A. Woll, Natarajan V. Bhanu, Weiming Bu, Patrick J. Loll, Antonio Suma, Roderic G. Eckenhoff, Manuel Covarrubias, Kimberly C. Grasty, Elaine Yang, Vincenzo Carnevale, and Benjamin A. Garcia
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Electrophysiology ,Photoaffinity labeling ,Chemistry ,Sodium channel ,Mutagenesis ,medicine ,Biophysics ,Binding site ,Propofol ,Function (biology) ,Ion channel ,medicine.drug - Abstract
Propofol, one of the most commonly used intravenous general anesthetics, modulates neuronal function by interacting with ion channels. The mechanisms that link propofol binding to the modulation of distinct ion channel states, however, are not understood. To tackle this problem, we investigated prokaryotic ancestors of eukaryotic voltage-gated Na+ channels (Navs) using unbiased photoaffinity labeling with a photoacitivatable propofol analog (AziPm), electrophysiological methods and mutagenesis. The results directly demonstrate conserved propofol binding sites involving the S4 voltage sensors and the S4-S5 linkers in NaChBac and NavMs, and also suggest state-dependent changes at these sites. Then, using molecular dynamics simulations to elucidate the structural basis of propofol modulation, we show that the S4 voltage sensors and the S4-S5 linkers shape two distinct propofol binding sites in a conformation-dependent manner. These interactions help explain how propofol binding promotes activation-coupled inactivation to inhibit Nav channel function.
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- 2020
4. Propofol inhibits prokaryotic voltage-gated Na+ channels by promoting activation-coupled inactivation
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Roderic G. Eckenhoff, Vincenzo Carnevale, Elaine Yang, Manuel Covarrubias, and Daniele Granata
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0301 basic medicine ,Voltage-gated ion channel ,Physiology ,Chemistry ,Kinetics ,Time constant ,Gating ,3. Good health ,03 medical and health sciences ,030104 developmental biology ,Reaction rate constant ,Mechanism of action ,medicine ,Biophysics ,Patch clamp ,medicine.symptom ,Propofol ,Research Articles ,Research Article ,medicine.drug - Abstract
Despite extensive use in clinical practice, the mechanisms of propofol action on sodium channels are not fully understood. Yang et al. incorporate complementary biophysical approaches (electrophysiology and molecular dynamics simulations) to demonstrate that propofol inhibits two prokaryotic voltage-gated sodium channels, NaChBac and NavMs, by modulating both activation and inactivation gating., Propofol is widely used in the clinic for the induction and maintenance of general anesthesia. As with most general anesthetics, however, our understanding of its mechanism of action remains incomplete. Local and general anesthetics largely inhibit voltage-gated Na+ channels (Navs) by inducing an apparent stabilization of the inactivated state, associated in some instances with pore block. To determine the biophysical and molecular basis of propofol action in Navs, we investigated NaChBac and NavMs, two prokaryotic Navs with distinct voltage dependencies and gating kinetics, by whole-cell patch clamp electrophysiology in the absence and presence of propofol at clinically relevant concentrations (2–10 µM). In both Navs, propofol induced a hyperpolarizing shift of the pre-pulse inactivation curve without any significant effects on recovery from inactivation at strongly hyperpolarized voltages, demonstrating that propofol does not stabilize the inactivated state. Moreover, there was no evidence of fast or slow pore block by propofol in a non-inactivating NaChBac mutant (T220A). Propofol also induced hyperpolarizing shifts of the conductance-voltage relationships with negligible effects on the time constants of deactivation at hyperpolarized voltages, indicating that propofol does not stabilize the open state. Instead, propofol decreases the time constants of macroscopic activation and inactivation. Adopting a kinetic scheme of Nav gating that assumes preferential closed-state recovery from inactivation, a 1.7-fold acceleration of the rate constant of activation and a 1.4-fold acceleration of the rate constant of inactivation were sufficient to reproduce experimental observations with computer simulations. In addition, molecular dynamics simulations and molecular docking suggest that propofol binding involves interactions with gating machinery in the S4–S5 linker and external pore regions. Our findings show that propofol is primarily a positive gating modulator of prokaryotic Navs, which ultimately inhibits the channels by promoting activation-coupled inactivation.
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- 2018
5. Propofol inhibits the voltage-gated sodium channel NaChBac at multiple sites
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Pei Tang, Daniele Granata, Roderic G. Eckenhoff, Elaine Yang, Kellie A. Woll, Vasyl Bondarenko, William P. Dailey, Yali Wang, Yan Xu, Michael L. Klein, Manuel Covarrubias, Vincenzo Carnevale, and Marta M. Wells
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0301 basic medicine ,Physiology ,Chemistry ,Sodium channel ,Inhibitory postsynaptic potential ,3. Good health ,03 medical and health sciences ,Electrophysiology ,030104 developmental biology ,Docking (molecular) ,Anesthetic ,Biophysics ,medicine ,Patch clamp ,Binding site ,Propofol ,Research Articles ,Research Article ,medicine.drug - Abstract
General anesthetics inhibit voltage-gated sodium channels by unknown molecular mechanisms. Using computation-guided NMR and electrophysiology analyses, Wang et al. show that propofol binds to the prokaryotic sodium channel NaChBac at multiple distinct sites., Voltage-gated sodium (NaV) channels are important targets of general anesthetics, including the intravenous anesthetic propofol. Electrophysiology studies on the prokaryotic NaV channel NaChBac have demonstrated that propofol promotes channel activation and accelerates activation-coupled inactivation, but the molecular mechanisms of these effects are unclear. Here, guided by computational docking and molecular dynamics simulations, we predict several propofol-binding sites in NaChBac. We then strategically place small fluorinated probes at these putative binding sites and experimentally quantify the interaction strengths with a fluorinated propofol analogue, 4-fluoropropofol. In vitro and in vivo measurements show that 4-fluoropropofol and propofol have similar effects on NaChBac function and nearly identical anesthetizing effects on tadpole mobility. Using quantitative analysis by 19F-NMR saturation transfer difference spectroscopy, we reveal strong intermolecular cross-relaxation rate constants between 4-fluoropropofol and four different regions of NaChBac, including the activation gate and selectivity filter in the pore, the voltage sensing domain, and the S4–S5 linker. Unlike volatile anesthetics, 4-fluoropropofol does not bind to the extracellular interface of the pore domain. Collectively, our results show that propofol inhibits NaChBac at multiple sites, likely with distinct modes of action. This study provides a molecular basis for understanding the net inhibitory action of propofol on NaV channels.
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- 2018
6. Ascending Aortic Cannulation in Acute Type A Dissection Repair
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Y. Joseph Woo, Alen Trubelja, Nimesh D. Desai, John R. Frederick, Wilson Y. Szeto, Joseph E. Bavaria, Alberto Pochettino, and Elaine Yang
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Pulmonary and Respiratory Medicine ,Aortic dissection ,Arterial inflow ,medicine.medical_specialty ,business.industry ,Classification scheme ,medicine.disease ,Aortic Aneurysm ,Catheterization ,Surgery ,Aortic Dissection ,Dissection ,Aneurysm ,Current practice ,Acute type ,medicine.artery ,Ascending aorta ,cardiovascular system ,medicine ,Humans ,Cardiology and Cardiovascular Medicine ,business ,Aorta ,Retrospective Studies - Abstract
Femoral and axillary cannulation for arterial inflow in acute type A aortic dissection are the most commonly used cannulation strategies in current practice. More recently, our group and others have successfully used a central cannulation technique with excellent results. Although this approach has been described, specific technical details have not been clearly defined. In addition, the ideal anatomic characteristics of different types of aortic dissections amenable to central cannulation have not been delineated. The purpose of this brief communication is to describe the technical and procedural details specific to cannulation of the dissected ascending aorta and to propose a classification scheme of ascending aortic dissection anatomy based on difficulty of central cannulation.
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- 2013
7. Inhibition of a Voltage-Gated Sodium Channel by Propofol Involves Modulation of Slow Inactivation
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Elaine Yang, Vincenzo Carnevale, and Manuel Covarrubias
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Electrophysiology ,Isoflurane ,Chemistry ,Sodium channel ,Anesthetic ,medicine ,Time constant ,Biophysics ,Pharmacology ,Propofol ,Sevoflurane ,EC50 ,medicine.drug - Abstract
Voltage-gated sodium channels (Navs), critical for action potential generation and propagation in the central nervous system, are inhibited by clinically relevant concentrations of many general anesthetics. The molecular mechanism for this inhibition, however, is still largely unclear. Here, we investigated the electrophysiological response of the bacterial voltage-gated sodium channel NaChBac to the widely used injectable anesthetic propofol at concentrations near the clinically relevant EC50. At 2 μM, propofol induces a −7.0 ± 1.1 mV leftward shift of the steady-state inactivation curve (V½ control = −49 ± 2.2 mV, V½ 2μM = −56 ± 2.3 mV, n=3) and a ∼24% decrease in the time constant of inactivation at −10 mV (τ control = 188 ± 26 ms, τ 2μM = 142 ± 11 ms, n=3). 5 μM propofol induces a −7.0 ± 1.3 mV leftward shift of the steady-state inactivation curve (V½ control = −55 ± 0.6 mV, V½ 5μM = −62 ± 1.2 mV, n=8) and a ∼37% decrease in the time constant of inactivation at −10 mV (τ control = 187 ± 8.7ms, τ 5μM = 117 ± 5.5 ms, n=8). Consistent with behavior in response to isoflurane (Ouyang et al., 2007) and sevoflurane (Barber et al., 2014), propofol inhibits channel function by promoting and stabilizing the inactivated state. Structurally diverse general anesthetics might inhibit NaChBac by acting on slow inactivation, a mechanism also present in mammalian Navs that possibly involves the pore domain. Therefore, to assess the role of slow inactivation in the mechanism of general anesthetic action, we are evaluating sites in the S6 helix that alter inactivation kinetics (G219, T220, and F227). Furthermore, aided by molecular dynamics simulations, we are validating putative general anesthetic binding sites in the pore domain of NaChBac.
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- 2016
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8. Propofol is a Potent Gating Modifier of Voltage-Gated Sodium Channels
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Elaine Yang, Roderic G. Eckenhoff, Daniele Granata, Manuel Covarrubias, and Vincenzo Carnevale
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Chemistry ,Sodium channel ,Biophysics ,medicine ,Gating ,Propofol ,medicine.drug - Published
- 2017
9. Sustained Release of Engineered Stromal Cell–Derived Factor 1-α From Injectable Hydrogels Effectively Recruits Endothelial Progenitor Cells and Preserves Ventricular Function After Myocardial Infarction
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Philip F. Hsiao, Jay Patel, John W. MacArthur, Elaine Yang, Yasuhiro Shudo, Y. Joseph Woo, William Hiesinger, Brendan P. Purcell, Pavan Atluri, Kelsey Lloyd, Jason A. Burdick, Alex Fairman, Jeffrey E. Cohen, and Alen Trubelja
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Male ,medicine.medical_specialty ,Stromal cell ,Angiogenesis ,Myocardial Infarction ,Endothelial progenitor cell ,Article ,Ventricular Function, Left ,Injections ,chemistry.chemical_compound ,In vivo ,Cell Movement ,Physiology (medical) ,Hyaluronic acid ,medicine ,Animals ,Stromal cell-derived factor 1 ,Progenitor cell ,Rats, Wistar ,biology ,business.industry ,Stem Cells ,Endothelial Cells ,Hydrogels ,Chemokine CXCL12 ,Surgery ,Cell biology ,Rats ,chemistry ,Delayed-Action Preparations ,Self-healing hydrogels ,biology.protein ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background— Exogenously delivered chemokines have enabled neovasculogenic myocardial repair in models of ischemic cardiomyopathy; however, these molecules have short half-lives in vivo. In this study, we hypothesized that the sustained delivery of a synthetic analog of stromal cell–derived factor 1-α (engineered stromal cell–derived factor analog [ESA]) induces continuous homing of endothelial progenitor cells and improves left ventricular function in a rat model of myocardial infarction. Methods and Results— Our previously designed ESA peptide was synthesized by the addition of a fluorophore tag for tracking. Hyaluronic acid was chemically modified with hydroxyethyl methacrylate to form hydrolytically degradable hydrogels through free-radical–initiated crosslinking. ESA was encapsulated in hyaluronic acid hydrogels during gel formation, and then ESA release, along with gel degradation, was monitored for more than 4 weeks in vitro. Chemotactic properties of the eluted ESA were assessed at multiple time points using rat endothelial progenitor cells in a transwell migration assay. Finally, adult male Wistar rats (n=33) underwent permanent ligation of the left anterior descending (LAD) coronary artery, and 100 µL of saline, hydrogel alone, or hydrogel+25 µg ESA was injected into the borderzone. ESA fluorescence was monitored in animals for more than 4 weeks, after which vasculogenic, geometric, and functional parameters were assessed to determine the therapeutic benefit of each treatment group. ESA release was sustained for 4 weeks in vitro, remained active, and enhanced endothelial progenitor cell chemotaxis. In addition, ESA was detected in the rat heart >3 weeks when delivered within the hydrogels and significantly improved vascularity, ventricular geometry, ejection fraction, cardiac output, and contractility compared with controls. Conclusions— We have developed a hydrogel delivery system that sustains the release of a bioactive endothelial progenitor cell chemokine during a 4-week period that preserves ventricular function in a rat model of myocardial infarction.
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- 2013
10. Mathematically-Engineered Stromal Cell-Derived Factor 1alpha Stem Cell Cytokine Analogue Enhances Mechanical Properties of Infarcted Myocardium
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Alen Trubelja, Pavan Atluri, Elaine Yang, William Hiesinger, Joseph J. Sarver, John W. MacArthur, Philip F. Hsiao, Yasuhiro Shudo, Alexander S. Fairman, and Y. Joseph Woo
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Pulmonary and Respiratory Medicine ,Male ,medicine.medical_specialty ,Cardiac output ,Cardiotonic Agents ,Time Factors ,Myocardial Infarction ,Infarction ,030204 cardiovascular system & hematology ,Article ,Injections ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Tensile Strength ,medicine ,Animals ,Ventricular Function ,Myocardial infarction ,Rats, Wistar ,Ventricular remodeling ,Ultrasonography ,Ejection fraction ,Ventricular Remodeling ,business.industry ,Myocardium ,Stroke Volume ,Recovery of Function ,medicine.disease ,Myocardial Contraction ,Chemokine CXCL12 ,3. Good health ,Surgery ,Biomechanical Phenomena ,Rats ,Disease Models, Animal ,medicine.anatomical_structure ,Ventricle ,030220 oncology & carcinogenesis ,Heart failure ,Drug Design ,Cardiology ,Computer-Aided Design ,business ,Cardiology and Cardiovascular Medicine ,Artery - Abstract
Objective The biomechanical response to a myocardial infarction consists of ventricular remodeling that leads to dilatation, loss of contractile function, abnormal stress patterns, and ultimately heart failure. We hypothesized that intramyocardial injection of our previously designed pro-angiogenic chemokine, an engineered stromal cell–derived factor-1α analog (ESA), improves mechanical properties of the heart after infarction. Methods Male rats (n = 54) underwent either sham surgery (n = 17) with no coronary artery ligation or ligation of the left anterior descending artery (n = 37). The rats in the myocardial infarction group were then randomized to receive either saline (0.1 mL, n = 18) or ESA (6 μg/kg, n = 19) injected into the myocardium at 4 predetermined spots around the border zone. Echocardiograms were performed preoperatively and before the terminal surgery. After 4 weeks, the hearts were explanted and longitudinally sectioned. Uniaxial tensile testing was completed using an Instron 5543 Microtester. Optical strain was evaluated using custom image acquisition software, Digi-Velpo, and analyzed in MATLAB. Results Compared with the saline control group at 4 weeks, the ESA-injected hearts had a greater ejection fraction (71.8% ± 9.0% vs 55.3% ± 12.6%, P = .0004), smaller end-diastolic left ventricular internal dimension (0.686 ± 0.110 cm vs 0.763 ± 0.160 cm, P = .04), greater cardiac output (36 ± 11.6 mL/min vs 26.9 ± 7.3 mL/min, P = .05), and a lower tensile modulus (251 ± 56 kPa vs 301 ± 81 kPa, P = .04). The tensile modulus for the sham group was 195 ± 56 kPa, indicating ESA injection results in a less stiff ventricle. Conclusions Direct injection of ESA alters the biomechanical response to myocardial infarction, improving the mechanical properties in the postinfarct heart.
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- 2013
11. Lipid profiling identifies a triacylglycerol signature of insulin resistance and improves diabetes prediction in humans
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Robert E. Gerszten, Clary B. Clish, Caroline S. Fox, Jose C. Florez, Susan Cheng, Martin G. Larson, Elizabeth L. McCabe, Gregory D. Lewis, Elaine Yang, Eugene P. Rhee, Ramachandran S. Vasan, Thomas J. Wang, Laurie A. Farrell, Christopher J. O'Donnell, Geoffrey A. Walford, and Steven A. Carr
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Adult ,Male ,medicine.medical_specialty ,Diabetes risk ,medicine.medical_treatment ,Type 2 diabetes ,Biology ,Insulin resistance ,Predictive Value of Tests ,Risk Factors ,Diabetes mellitus ,Internal medicine ,medicine ,Humans ,Insulin ,Risk factor ,Triglycerides ,Aged ,Dyslipidemias ,Glucose tolerance test ,medicine.diagnostic_test ,Molecular Structure ,General Medicine ,Glucose Tolerance Test ,Middle Aged ,medicine.disease ,Lipids ,Endocrinology ,Diabetes Mellitus, Type 2 ,Case-Control Studies ,Exercise Test ,lipids (amino acids, peptides, and proteins) ,Female ,Insulin Resistance ,Dyslipidemia ,Biomarkers ,Research Article - Abstract
Dyslipidemia is an independent risk factor for type 2 diabetes, although exactly which of the many plasma lipids contribute to this remains unclear. We therefore investigated whether lipid profiling can inform diabetes prediction by performing liquid chromatography/mass spectrometry-based lipid profiling in 189 individuals who developed type 2 diabetes and 189 matched disease-free individuals, with over 12 years of follow up in the Framingham Heart Study. We found that lipids of lower carbon number and double bond content were associated with an increased risk of diabetes, whereas lipids of higher carbon number and double bond content were associated with decreased risk. This pattern was strongest for triacylglycerols (TAGs) and persisted after multivariable adjustment for age, sex, BMI, fasting glucose, fasting insulin, total triglycerides, and HDL cholesterol. A combination of 2 TAGs further improved diabetes prediction. To explore potential mechanisms that modulate the distribution of plasma lipids, we performed lipid profiling during oral glucose tolerance testing, pharmacologic interventions, and acute exercise testing. Levels of TAGs associated with increased risk for diabetes decreased in response to insulin action and were elevated in the setting of insulin resistance. Conversely, levels of TAGs associated with decreased diabetes risk rose in response to insulin and were poorly correlated with insulin resistance. These studies identify a relationship between lipid acyl chain content and diabetes risk and demonstrate how lipid profiling could aid in clinical risk assessment.
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- 2011
12. Metabolic Signatures of Exercise in Human Plasma
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Clary B. Clish, Marc J. Semigran, Frederick P. Roth, Gregory D. Lewis, Marc S. Sabatine, Robert E. Gerszten, Malissa J. Wood, Maryann E. Martinovic, Eugene P. Rhee, Elaine Yang, Glenn C. Rowe, Aarti Asnani, Elizabeth L. McCabe, Ramachandran S. Vasan, Laurie A. Farrell, Susan Cheng, Xu Shi, Amanda Souza, Steven A. Carr, Rahul C. Deo, Zoltan Arany, Thomas J. Wang, and David M. Systrom
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Adult ,Male ,medicine.medical_specialty ,Metabolite ,Biology ,Article ,Cell Line ,Mice ,chemistry.chemical_compound ,Metabolomics ,Internal medicine ,Pantothenic acid ,Nuclear Receptor Subfamily 4, Group A, Member 1 ,medicine ,Animals ,Humans ,Lipolysis ,Exercise physiology ,Muscle, Skeletal ,Exercise ,Beta oxidation ,Aged ,General Medicine ,Middle Aged ,Citric acid cycle ,Blood ,Endocrinology ,chemistry ,Niacinamide ,Energy Metabolism ,Psychomotor Performance - Abstract
Exercise provides numerous salutary effects, but our understanding of how these occur is limited. To gain a clearer picture of exercise-induced metabolic responses, we have developed comprehensive plasma metabolite signatures by using mass spectrometry to measure >200 metabolites before and after exercise. We identified plasma indicators of glycogenolysis (glucose-6-phosphate), tricarboxylic acid cycle span 2 expansion (succinate, malate, and fumarate), and lipolysis (glycerol), as well as modulators of insulin sensitivity (niacinamide) and fatty acid oxidation (pantothenic acid). Metabolites that were highly correlated with fitness parameters were found in subjects undergoing acute exercise testing and marathon running and in 302 subjects from a longitudinal cohort study. Exercise-induced increases in glycerol were strongly related to fitness levels in normal individuals and were attenuated in subjects with myocardial ischemia. A combination of metabolites that increased in plasma in response to exercise (glycerol, niacinamide, glucose-6-phosphate, pantothenate, and succinate) up-regulated the expression of nur77, a transcriptional regulator of glucose utilization and lipid metabolism genes in skeletal muscle in vitro. Plasma metabolic profiles obtained during exercise provide signatures of exercise performance and cardiovascular disease susceptibility, in addition to highlighting molecular pathways that may modulate the salutary effects of exercise.
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- 2010
13. Metabolite profiling of blood from individuals undergoing planned myocardial infarction reveals early markers of myocardial injury
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Igor F. Palacios, Michael A. Fifer, Xu Shi, Laurie A. Farrell, Hasmik Keshishian, Anthony Rosenzweig, Elaine Yang, Emerson Liu, Steven A. Carr, Murat Tasan, Robert E. Gerszten, Ru Wei, Vamsi K. Mootha, Gregory D. Lewis, Gabriel F. Berriz, Jiangyong Min, Oded Shaham, Terri Addona, Arvind Ramanathan, Aarti Asnani, Christian Baumgartner, Marcoli Cyrille, Patricia A. Lowry, Maryann E. Martinovic, Frederick P. Roth, and Marc S. Sabatine
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Male ,medicine.medical_specialty ,Time Factors ,Myocardial Infarction ,Infarction ,Disease ,Pentose phosphate pathway ,Metabolomics ,Septal Ablation ,Isotopes ,Internal medicine ,Medicine ,Animals ,Humans ,Myocytes, Cardiac ,Derivation ,Myocardial infarction ,Coronary sinus ,Cells, Cultured ,Aged ,business.industry ,Coronary Sinus ,Reproducibility of Results ,General Medicine ,Middle Aged ,Reference Standards ,medicine.disease ,Rats ,Kinetics ,Heart Injuries ,Technical Advance ,Cardiology ,Female ,business ,Biomarkers - Abstract
Emerging metabolomic tools have created the opportunity to establish metabolic signatures of myocardial injury. We applied a mass spectrometry–based metabolite profiling platform to 36 patients undergoing alco-hol septal ablation treatment for hypertrophic obstructive cardiomyopathy, a human model of planned myo-cardial infarction (PMI). Serial blood samples were obtained before and at various intervals after PMI, with patients undergoing elective diagnostic coronary angiography and patients with spontaneous myocardial infarction (SMI) serving as negative and positive controls, respectively. We identified changes in circulating levels of metabolites participating in pyrimidine metabolism, the tricarboxylic acid cycle and its upstream con-tributors, and the pentose phosphate pathway. Alterations in levels of multiple metabolites were detected as early as 10 minutes after PMI in an initial derivation group and were validated in a second, independent group of PMI patients. A PMI-derived metabolic signature consisting of aconitic acid, hypoxanthine, trimethylamine N-oxide, and threonine differentiated patients with SMI from those undergoing diagnostic coronary angiogra-phy with high accuracy, and coronary sinus sampling distinguished cardiac-derived from peripheral metabolic changes. Our results identify a role for metabolic profiling in the early detection of myocardial injury and sug-gest that similar approaches may be used for detection or prediction of other disease states.
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- 2008
14. Health care costs of adults treated for attention-deficit/hyperactivity disorder who received alternative drug therapies
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Eric Q. Wu, David Mallet, Huabin F. Zhang, Howard G. Birnbaum, Elaine Yang, and Jasmina I. Ivanova
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Drug ,Adult ,Male ,medicine.medical_specialty ,Time Factors ,Databases, Factual ,media_common.quotation_subject ,MEDLINE ,Pharmaceutical Science ,Pharmacy ,Atomoxetine Hydrochloride ,Health care ,medicine ,Attention deficit hyperactivity disorder ,Humans ,Psychiatry ,Amphetamine ,media_common ,Insurance, Health ,Adrenergic Uptake Inhibitors ,Propylamines ,business.industry ,Methylphenidate ,Health Policy ,Atomoxetine ,Amphetamines ,Managed Care Programs ,Reproducibility of Results ,Health Care Costs ,Middle Aged ,medicine.disease ,Insurance, Pharmaceutical Services ,Attention Deficit Disorder with Hyperactivity ,Delayed-Action Preparations ,Multivariate Analysis ,Costs and Cost Analysis ,Central Nervous System Stimulants ,Female ,business ,medicine.drug ,Atomoxetine hydrochloride - Abstract
Many therapies exist for treating adult attention-deficit/hyperactivity disorder (ADHD), also referred to as attention-deficit disorder (ADD), but there is no research regarding cost differences associated with initiating alternative ADD/ADHD drug therapies in adults.To compare from the perspective of a large self-insured employer the risk-adjusted direct health care costs associated with 3 alternative drug therapies for ADD in newly treated patients: extended-release methylphenidate (osmotic release oral system-MPH), mixed amphetamine salts extended release (MAS-XR), or atomoxetine.We analyzed data from a US claims database of 5 million beneficiaries from 31 large self-insured employers (1999-2004). Analysis was restricted to adults aged 18 to 64 years with at least 1 diagnosis of ADD/ADHD (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 314.0x--attention deficit disorder; 314.00--attention deficit disorder without hyperactivity; or 314.01--attention-deficit disorder with hyperactivity) and at least 1 pharmacy claim for OROS-MPH, MAS-XR, or atomoxetine identified using National Drug Codes. In preliminary analysis, we calculated the duration of index ADHD drug therapy as time from index therapy initiation to a minimum 60-day gap. Because the median duration of index ADHD drug therapy was found to be approximately 90 days, the primary measures were total direct medical plus drug costs and medical-only costs computed over 6 months following therapy initiation. Adults were required to have continuous eligibility 6 months before and 6 months after their latest drug therapy initiation and no ADHD therapy during the previous 6 months. Cost was measured as the payment amount made by the health plan to the provider rather than billed charges, and it excluded patient copayments and deductibles. Medical costs included costs incurred for all-cause inpatient and outpatient/other services. Costs were adjusted for inflation to 2004 U.S. dollars using the consumer price index for medical care. T tests were used for descriptive cost comparisons. Generalized linear models (GLMs) were used to compare costs of adults receiving alternative therapies, adjusting for demographic characteristics, substance abuse, depression, and the Charlson Comorbidity Index.Of the 4,569 patients who received 1 of these 3 drug therapies for ADHD, 31.8% received OROS-MPH for a median duration of 99 days of therapy, 34.0% received MAS-XR for a median 128 days, and 34.2% received atomoxetine for a median 86 days. In the 6-month follow-up period, the mean (standard deviation) total medical and drug costs were $2,008 ($3,231) for OROS-MPH, $2,169 ($4,828) for MAS-XR, and $2,540 ($4,269) for atomoxetine-treated adults. The GLM for patient characteristics suggested that 6-month, risk-adjusted mean medical costs, excluding drug costs, for adults treated with OROS-MPH were $142 less (10.4%, $1,220 vs. $1,362) compared with MAS-XR (P =0.022) and $132 less (9.8%, $1,220 vs. $1,352) compared with atomoxetine (P =0.033); risk-adjusted mean medical costs were not significantly different between MAS-XR and atomoxetine. The GLM comparison of risk-adjusted total direct costs, including drug cost, was on average $156 less (8.0%, $1,782 vs. $1,938) for OROS-MPH compared with MAS-XR (P = 0.017) and $226 less (11.3%, $1,782 vs. $2,008) compared with atomoxetine (P0.001); the risk-adjusted total direct costs were not significantly different between MAS-XR and atomoxetine. Two high-cost outliers (greater than 99.96th percentile, 1 each for OROS-MPH and atomoxetine) accounted for $47 (30%) of the $156 cost difference between OROS-MPH and MAS-XR and $11 (5%) of the $226 cost difference between OROS-MPH and atomoxetine, and the medical diagnoses for the highest-cost claims for these 2 outlier patients were unrelated to ADHD.After adjusting for patient characteristics including substance abuse, depression, and the Charlson Comorbidity Index, adults treated with OROS-MPH had, on average, slightly lower medical and total medical and drug costs than those treated with MAS-XR or atomoxetine over the 6-month period after drug therapy initiation. Approximately 30% of the cost difference compared with MAS-XR was attributable to 1 high-cost outlier with medical diagnoses for the highest-cost claim that were unrelated to ADHD.
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- 2007
15. Neuromuscular blocking agents used with antibiotics
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Dora T. Hsu, Maurice Lippmann, and Elaine Yang
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medicine.medical_specialty ,Vecuronium Bromide ,medicine.drug_class ,business.industry ,Pain medicine ,Antibiotics ,Cefazolin ,Tubocurarine ,General Medicine ,Neuromuscular Blocking Agents ,Anesthesiology and Pain Medicine ,Anesthesiology ,Anesthesia ,medicine ,Tobramycin ,Atracurium ,Humans ,Gentamicin ,Drug Interactions ,Gentamicins ,business ,medicine.drug - Published
- 1990
16. Focal contracture following injection of succinylcholine in patients with peripheral nerve injury
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Elaine Yang, Ronald L. Katz, and Chingmuh Lee
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Adult ,Male ,medicine.medical_specialty ,Succinylcholine ,Wrist ,Peripheral Nerve Injuries ,medicine ,Spastic ,Humans ,Aged ,Muscle contracture ,business.industry ,General Medicine ,Middle Aged ,Nerve injury ,Hand ,medicine.disease ,Neuromuscular Blocking Agents ,Muscle Denervation ,Surgery ,Anesthesiology and Pain Medicine ,medicine.anatomical_structure ,Anesthesia ,Peripheral nerve injury ,Crush injury ,Female ,Contracture ,medicine.symptom ,business ,Muscle Contraction - Abstract
Focal muscle contracture in the limb following sytemic administration of depolarizing neuromuscular blocking agents have been demonstrated experimentally with transection or crush injury of the nerve, but has rarely been observed clinically in patients with partial peripheral nerve injury. Three cases of spastic response in the hand and wrist are described in patients with subclinical chronic, subacute, and acute nerve injury, to document the occurrence of this phenomenon under various circumstances.
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- 1977
17. Neuromuscular block by circulating D-tubocurarine residue following uptake and distribution
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Chingmuh Lee and Elaine Yang
- Subjects
Male ,Residue (complex analysis) ,medicine.medical_specialty ,Time Factors ,business.industry ,Neuromuscular Junction ,Tubocurarine ,General Medicine ,Serum concentration ,Synaptic Transmission ,D-Tubocurarine ,Anesthesiology and Pain Medicine ,Endocrinology ,Anesthesia ,Internal medicine ,medicine ,Cats ,Distribution (pharmacology) ,Animals ,Female ,business ,Muscle Contraction - Abstract
Serum concentration of d-tubocurarine decreases rapidly after intravenous injection because of uptake and distribution. The circulating residue of an ED 50 dose of d-tubocurarine five minutes after injection will produce no block in a previously unexposed neuromuscular junction. To produce a 50 per cent block with the circulating d-tubocurarine residue in a previously unexposed neuromuscular junction requires an initial injection of 2.5 x ED 50 dose. Five minutes after a dose 5 to 6 times the ED 50, the plasma d-tubocurarine residue is sufficient to produce a total block.
- Published
- 1977
18. Neuromuscular blocking effects of tobramycin, gentamicin, and cefazolin
- Author
-
Maurice Lippmann, Elaine Yang, Chingmuh Lee, and Eileen Au
- Subjects
Adult ,Male ,Adolescent ,Cefazolin ,Tubocurarine ,Succinylcholine ,Random Allocation ,medicine ,Tobramycin ,Potency ,Humans ,Drug Interactions ,Ulnar Nerve ,Aged ,business.industry ,Aminoglycoside ,Enflurane ,Middle Aged ,Electric Stimulation ,Neostigmine ,Anti-Bacterial Agents ,Atropine ,Anesthesiology and Pain Medicine ,Anesthesia ,Gentamicin ,Female ,Gentamicins ,Neuromuscular Blocking Agents ,business ,medicine.drug ,Muscle Contraction - Abstract
Forty patients (A.S.A. class I or II), 18 to 75 years of age, who were undergoing elective surgery were studied to determine the clinical and subclinical neuromuscular blocking effects of two antibiotics, tobramycin and gentamicin and to compare these effects with those produced by cefazolin, an aminoglycoside not known to produce paralysis. Patients were prospectively and randomly assigned in approximately equal numbers to one of four groups: group A received 1 mg/kg of tobramycin; group B, 1 mg/kg of gentamicin; group C, 500 mg of cefazolin; or group D, control (no antibiotic). Antibiotics were administered intravenously 45 minutes immediately preceding the study. The ulnar nerve was stimulated supramaximally and neuromuscular function was measured electromyographically. Anesthesia was induced with thiopental, 4 mg/kg IV, and maintained with endotracheal enflurane 1.0% to 1.5% (inspired) and N2O-O2 (2 L:1 L) after intubation. Succinylcholine (1 mg/kg) was administered after induction of anesthesia and the magnitude and duration of neuromuscular block monitored. d-Tubocurarine (0.1 mg/kg) was given 5 to 10 minutes after full recovery from succinylcholine and repeated as required. At the end of the operation, atropine, 0.02 mg/kg, and neostigmine, 0.4 mg/kg, were used to reverse the block. Base line neuromuscular data, duration of block of succinylcholine, and potency, duration of block, recovery rate, train-of-four fade, tetanic trend, response to double stimuli, post-tetanic effect, and reversibility of the subsequent d--tubocurarine-induced neuromuscular block were not significantly different (p less than 0.01) between any two groups. Tobramycin, gentamicin, and cefazolin, in recommended single doses, lack clinical neuromuscular blocking and subclinical relaxant-potentiating effects.
- Published
- 1982
19. Interactions of neuromuscular effects of edrophonium, alpha-bungarotoxin and beta-bungarotoxin
- Author
-
Elaine Yang, Ronald L. Katz, and Chingmuh Lee
- Subjects
animal structures ,Models, Neurological ,Neuromuscular transmission ,Neuromuscular Junction ,Edrophonium ,Pharmacology ,Synaptic Transmission ,chemistry.chemical_compound ,Medicine ,Animals ,Drug Interactions ,Denervation ,business.industry ,Neuromuscular Effects ,Alpha-Bungarotoxin ,Bungarotoxins ,Anesthesiology and Pain Medicine ,chemistry ,Mechanism of action ,beta-bungarotoxin ,Female ,Contracture ,medicine.symptom ,business ,Chickens ,medicine.drug ,Muscle Contraction - Abstract
Interactions of neuromuscular effects of edrophonium, alpha-bungarotoxin, and beta-bungarotoxin were studied in 12 chickens using the sciatic-gastrocnemius nerve-muscle preparation to elucidate the mechanism of action of each drug. Modification by the toxins of neuromuscular effects of edrophonium depended on the level of block pre-established by the toxins. Edrophonium-induced augmentation of muscle twitch ("facilitation") was decreased by both toxins. As the block reached 50 per cent, the facilitation was nearly abolished. Edrophonium-induced contracture of the muscle was blocked by alpha-bungarotoxin only. At 25 per cent block, it was no longer observable in five of six preparations. Beta-bungarotoxin enhanced the contracture. At complete block, the contracture reached 156 (SE 11, n = 6) per cent of control. The authors conclude that edrophonium facilitates neuromuscular transmission by a prejunctional mechanism and causes contracture of the chicken muscle by a post-junctional activation. The beta-bungarotoxin-blocked nerve-muscle preparation of the chicken is a model of acute denervation potentially useful for the study of drug effects on the postjunctional membrane.
- Published
- 1978
20. Predetermination of Dose Requirement of Pancuronium
- Author
-
Ronald L. Katz, Chingmuh Lee, and Elaine Yang
- Subjects
Adult ,Test dose ,Dose-Response Relationship, Drug ,Eye Movements ,Tetanus ,business.industry ,medicine.medical_treatment ,Muscle response ,Group ii ,Middle Aged ,medicine.disease ,Anesthesiology and Pain Medicine ,Anesthesia ,medicine ,Humans ,Intubation ,Female ,Pancuronium ,business - Abstract
The neuromuscular sensitivity of 71 patients (A.S.A. class I or II) was tested by scoring on a scale from 1 to 6 the ability to lift the upper eyelid 2 minutes after pretreatment with 1 mg of pancuronium. Subsequently, each patient also received an additional "intubation dose" pancuronium (in milligrams) equal to the eye-opening test score (group I), or either 1 mg (group II) or 2 mg (group III) in excess. The resultant depression of the neurally evoked muscle response of the little finger was quantified by another score (the response score) which allowed for assessment of neuromuscular block beyond the limit of 100% depression of the twitch. The criteria for the response score, in the response score, in the order of increasing magnitude of block, were: (1) visible twitch responses to all 4 of the train-of-four stimulation remained; (2) part of the train-of-four twitches was eliminated; (3) all twitches were eliminated; (4) tetanus was eliminated; (5) post-tetanic twitch following a 5-second 50 Hz tetanus was also eliminated; and (6) not even the post-tetanic twitch became elicitable again in 30 minutes. It was found that 1 mg of pancuronium depressed the eye-opening score to 4.0 +/- 0.2, from 5.1 +/- 0.1 (mean +/- SEM, p < 0.01). Following the additional "intubation dose" of pancuronium, patients in group I had an average response score of 2.2 +/- 0.3, those in group II a score of 3.4 +/- 0.2, and those in group III, a score of 4.8 +/- 0.6. Each additional 1 mg of pancuronium (increasing from group I to III) linearly increased the average response score. In terms of frequency response, patients in group I had more than a 50% change of being scored 1, while those in group II had a greater than 50% chance of being scored 3, 4, or 5, and those in group III had more than a 50% chance of being scored 6. It is concluded that sensitivity to pancuronium can be quantified by the ptotic response to a 1-mg test dose of pancuronium, and that a sensitivity-adjusted additional "intubation dose" of pancuronium can be predetermined in individual patients.
- Published
- 1980
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