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Opioid Withdrawal Signs And Symptoms In The Pediatric Patient During Opioid Tapering, Deborah Fisher Apr 2012

Opioid Withdrawal Signs And Symptoms In The Pediatric Patient During Opioid Tapering, Deborah Fisher

Theses and Dissertations

Opioids are used routinely in the pediatric intensive care population for analgesia, sedation, blunting of physiologic responses to stress, and safety. In children, physical dependence may occur in as little as two to three days of continuous opioid therapy. Once the child no longer needs the opioid, the medications are reduced over time. A review of the literature revealed that the majority of the published studies used either a neonatal opioid assessment tool or no assessment tool. A subsequent international survey of pediatric providers found a wide range of opioid tapering practices and sporadic use of opioid withdrawal instruments to …


Overexpression Of Serum Response Factor In Astrocytes Improves Neuronal Plasticity In A Model Of Fetal Alcohol Spectrum Disorders, Arco P. Paul Apr 2012

Overexpression Of Serum Response Factor In Astrocytes Improves Neuronal Plasticity In A Model Of Fetal Alcohol Spectrum Disorders, Arco P. Paul

Theses and Dissertations

Neuronal plasticity deficits underlie many of the neurobehavioral problems seen in Fetal Alcohol Spectrum Disorders (FASD). Recently, we showed that third trimester alcohol exposure lead to a persistent disruption in ocular dominance (OD) plasticity. For instance, few days of monocular deprivation results in a robust reduction of cortical regions responsive to the deprived eye in normal animals, but not in ferrets exposed early to alcohol. This plasticity deficit can be reversed if alcohol-exposed animals are treated with a phosphodiesterase type 1 (PDE1) inhibitor during the period of monocular deprivation. PDE1 inhibition can increase cAMP and cGMP levels, activating transcription factors …


Myelin Gene Expression: Implications For Alcohol Abuse And Dependence, Sean Farris Mar 2012

Myelin Gene Expression: Implications For Alcohol Abuse And Dependence, Sean Farris

Theses and Dissertations

Acute behavioral responses to ethanol have predictive value for determining an individual's risk of long-term drinking behavior. Although the neurobiology of alcohol abuse is complex, prior studies from our laboratory demonstrated differential myelin-associated gene expression (MAGE) in medial prefrontal cortex (PFC) as one potential mechanism influencing acute ethanol behaviors between C57BL/6J (B6) and DBA/2J (D2) mice. Our laboratory and others have also shown MAGE is reduced in PFC of alcoholics. Herein, I have extended these findings through expression profiling of PFC into chronic models of ethanol self-administration from non-human primates and mice. Together, these results suggest that regulation of MAGE …


Antinociceptive Effects Of Monoamine Reuptake Inhibitors In Assays Of Pain-Stimulated And Pain-Depressed Behaviors, Marisa Rosenberg Mar 2012

Antinociceptive Effects Of Monoamine Reuptake Inhibitors In Assays Of Pain-Stimulated And Pain-Depressed Behaviors, Marisa Rosenberg

Theses and Dissertations

ANTINOCICEPTIVE EFFECTS OF MONOAMINE REUPTAKE INHIBITORS IN ASSAYS OF PAIN-STIMULATED AND PAIN-DEPRESSED BEHAVIOR By Marisa B. Rosenberg A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science at Virginia Commonwealth University. Virginia Commonwealth University, 2012 Advisor: Sidney Stevens Negus, Ph.D. Professor, Department of Pharmacology/Toxicology Noxious stimuli can produce pain-related stimulation of some behaviors (e.g. withdrawal responses) and depression of other behaviors (e.g. feeding, locomotion, responding maintained by many types of positive reinforcement). Monoamine reuptake inhibitors are used clinically to treat depression and to manage some types of pain. This study examined the antinociceptive properties …


A Cellular Automata Model Of Enantiomer Interactions With Beta-Cyclodextrin, Desoi Darren Mar 2012

A Cellular Automata Model Of Enantiomer Interactions With Beta-Cyclodextrin, Desoi Darren

Theses and Dissertations

The binding mechanisms of molecules to cyclodextrins continues to be studied to better explain the interactions occurring. The majority of published models focus on one-to-one molecular binding thermodynamics to explain experimental results. They rely on physical concepts of energies and forces to guide the actions of molecules expressed mathematically in terms of differential and non-linear equations. These models are limited in scope due to their complexity and are not easily expanded to study many diverse analytes. Conversely, cellular automata uses simple mathematical idealizations of systems governed by deterministic and probabilistic rules that are easily adaptable to many types of molecular …


Factors Associated With Access To Palliative Care In A Large Urban Public Teaching Hospital With A Formal Hospital-Based Palliative Care Program, Leland Waters Mar 2012

Factors Associated With Access To Palliative Care In A Large Urban Public Teaching Hospital With A Formal Hospital-Based Palliative Care Program, Leland Waters

Theses and Dissertations

Hospital-based specialist palliative care services are designed to address the needs of critically ill patients by psychosocial and spiritual support, improving symptoms management, and offering discussions on goals of care. Integrating palliative care upstream in the care continuum for patients who eventually die in the hospital will help to address the many individualistic needs of the critically ill patient. The diffusion of specialist hospital-based palliative care services requires an understanding of patterns of utilization by patients. The purpose of this study was to examine the population characteristics of decedents who may or may not have utilized specialist palliative care services …


Use Of Procalcitonin As A Biomarker Of Bacterial Infection In Acute Liver Failure And Acute Liver Injury, Jody Balko Mar 2012

Use Of Procalcitonin As A Biomarker Of Bacterial Infection In Acute Liver Failure And Acute Liver Injury, Jody Balko

Theses and Dissertations

Infections in patients with acute liver failure (ALF) and acute liver injury (ALI) are a frequent occurrence. Because ALF and ALI patients share many of the same clinical features as patients with severe sepsis and septic shock, identifying an infection based upon clinical manifestations is extremely difficult. Bacterial culture and sensitivity reports require 24 to 72 hours to be finalized after the need for a culture is suspected and obtained. During this time period, ALF and ALI patients are either not receiving required antibiotic therapy, receiving antibiotic therapy that is not required or not appropriate for the infecting bacterial pathogen, …


Elevating Endogenous Cannabinoids Reduces Opioid Withdrawal In Mice, Divya Ramesh Feb 2012

Elevating Endogenous Cannabinoids Reduces Opioid Withdrawal In Mice, Divya Ramesh

Theses and Dissertations

Delta9-tetrahydrocannbinol (THC), the primary active constituent of Cannabis sativa, has long been known to reduce opioid withdrawal symptoms. Although THC produces most of its pharmacological actions through the activation of CB1 and CB2 cannabinoid receptors, the role these receptors play in reducing opioid withdrawal symptoms remains unknown. The endogenous cannabinoids, N-arachidonoylethanolamine (anandamide; AEA) and 2-arachidonylglycerol (2-AG), activate both cannabinoid receptors, but are rapidly metabolized by fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), respectively. The objective of this dissertation was to test whether increasing AEA or 2-AG, via inhibition of their respective hydrolytic enzymes, reduces morphine withdrawal symptoms in …


Comparison Of Steriplex™ Hc And Sodium Hypochlorite Cytotoxicity On Primary Human Gingival Fibroblasts, Jesse Harris Feb 2012

Comparison Of Steriplex™ Hc And Sodium Hypochlorite Cytotoxicity On Primary Human Gingival Fibroblasts, Jesse Harris

Theses and Dissertations

This study examined the cytotoxic effects of STERIPLEX™ HC (sBioMed, Orem, UT) and sodium hypochlorite (NaOCl) on human fibroblast cells in vitro. Fibroblasts exposed to various concentrations of NaOCl or STERIPLEX™ HC were visualized via light microscopy. Dilutions of either NaOCl or STERIPLEX™ HC that did not appear to disrupt the integrity of the cells were recorded for further analysis. Cells were then cultured and grown to confluence in five separate plates. A void was created down the middle of each plate. If the cells were viable, cellular confluence was seen. If nonviable, confluence of the cells did not occur. …


The Antimicrobial Effect Of Steriplex Hc In Comparison With Sodium Hypochlorite On Enterococcus Faecalis, Jonathan Coudron Feb 2012

The Antimicrobial Effect Of Steriplex Hc In Comparison With Sodium Hypochlorite On Enterococcus Faecalis, Jonathan Coudron

Theses and Dissertations

The study objective was to compare the antimicrobial activity of STERIPLEX™ HC with 5.25% sodium hypochlorite (NaOCl) at different dilutions (50%, 25%, 10%, 1%, 0.1%) and different time intervals (1, 3, 5 minutes) on Enterococcus faecalis. All data was analyzed using an ANOVA. The 50%, 25%, and 10% dilutions of both disinfectants reduced the colony forming unit (CFU) count to below the limit of detection (50 CFU/ml) after one minute. The 1% dilutions at each of the time intervals show NaOCl was significantly more effective than STERIPLEX™ HC (all Ps < .0001) in reducing the CFU/ml count. The 0.1% dilutions of NaOCl and STERIPLEX™ HC at 1 minute, were not different (P = 0.7808), while at 3 minutes and 5 minutes NaOCl was significantly more effective (P = 0.0098 and P < .0001, respectively).


The Role Of Calcineurin In Dendritic Remodeling And Epileptogenesis In A Rat Model Of Traumatic Brain Injury, John Campbell Feb 2012

The Role Of Calcineurin In Dendritic Remodeling And Epileptogenesis In A Rat Model Of Traumatic Brain Injury, John Campbell

Theses and Dissertations

Traumatic brain injury (TBI), a leading cause of death and disability in the United States, causes potentially preventable damage in part through the dysregulation of neural calcium levels. This dysregulation likely affects the activity of the calcium-sensitive phosphatase, calcineurin, with serious implications for neural function. To test this possibility, the present study characterized the role of calcineurin in a rat model of brain trauma, the lateral fluid percussion injury model. Golgi-Cox histochemistry revealed an acute post-TBI loss and delayed overgrowth of dendritic spines on principal cortical cells. The spine loss appeared to require calcineurin activity, since administering a calcineurin inhibitor, …


Dynamics Of Substrate Interactions In Trna (M1g37) Methyltransferase: Implications For Drug Discovery, Maria Kiouppis Palesis Feb 2012

Dynamics Of Substrate Interactions In Trna (M1g37) Methyltransferase: Implications For Drug Discovery, Maria Kiouppis Palesis

Theses and Dissertations

The bacterial enzyme t-RNA (m1G37) methyltransferase (TrmD) is an ideal anti-microbial drug target since it is found in all eubacteria, serves an essential role during protein synthesis, and shares very little sequence or structural homology with its eukaryotic counterpart, Trm5. TrmD, a homodimeric protein, methylates the G37 nucleotide of tRNA using S-adenosyl-L-methionine (SAM) as the methyl donor and thus enables proper codon-anticodon alignment during translation. The two deeply buried binding sites for SAM seen in X-ray crystallography suggest that significant conformational changes must occur for substrate binding and catalytic turnover. Results from molecular dynamics simulations implicate a flexible loop region …


Effects Of Early Alcohol Exposure On Ocular Dominance Plasticity, Crystal Lantz Jan 2012

Effects Of Early Alcohol Exposure On Ocular Dominance Plasticity, Crystal Lantz

Theses and Dissertations

Fetal alcohol spectrum disorder is the leading cause of mental retardation in the western world. It is associated with learning and sensory deficits. Some of these deficits are a result of faulty neuronal plasticity. Previously our lab has used ferrets to demonstrate that alcohol exposure during the third trimester of human gestation results in impaired ocular dominance plasticity (ODP). Here we have transferred this model to mice. Mice, treated with 5 mg/kg of ethanol on postnatal days 5, 7 and 9, exhibit a lack of ODP plasticity after 10 days of monocular deprivation (MD) during the critical period of visual …


Quantitative Genetic Methods To Dissect Heterogeneity In Complex Traits, T. Bernard Bigdeli Jan 2012

Quantitative Genetic Methods To Dissect Heterogeneity In Complex Traits, T. Bernard Bigdeli

Theses and Dissertations

Etiological models of complex disease are elusive[46, 33, 9], as are consistently replicable findings for major genetic susceptibility loci[54, 14, 15, 24]. Commonly-cited explanations invoke low-frequency genomic variation[41], allelic heterogeneity at susceptibility loci[33, 30], variable etiological trajectories[18, 17], and epistatic effects between multiple loci; these represent among the most methodologically-challenging issues in molecular genetic studies of complex traits. The response has been con- sistently reactionary—hypotheses regarding the relative contributions of known func- tional elements, or emphasizing a greater role of rare variation[46, 33] have undergone periodic revision, driving increasingly collaborative efforts to ascertain greater numbers of participants and which assay …


Biobehavioral Correlates In Fibromyalgia, Ann Trivigno Mcnallen Jan 2012

Biobehavioral Correlates In Fibromyalgia, Ann Trivigno Mcnallen

Theses and Dissertations

Introduction: Fibromyalgia (FMS) is a chronic pain syndrome characterized by non-restorative sleep, and fatigue. Over 75% of individuals with FMS complain of poor sleep quality and fatigue. These have been ranked by patients with FMS as having great impact on quality of life. A literature review suggested that poor sleep quality may be a predictor of increased stress and FMS symptom onset in those affected. However, no experimental studies have demonstrated a causal relationship between poor sleep and stress in people with FMS. Methods: Using a single stage cross-sectional design, the primary study aim was to compare 25 women with …


The Role Of Fyn And B-Cell Expressed Adam10 In Early B Cell Development, Germinal Center Formation And Terminal B Cell Differentiation, Natalia Chaimowitz Jan 2012

The Role Of Fyn And B-Cell Expressed Adam10 In Early B Cell Development, Germinal Center Formation And Terminal B Cell Differentiation, Natalia Chaimowitz

Theses and Dissertations

In these studies we sought to determine the role of Fyn kinase and ADAM10 in B cell biology. A disintegrin and metalloproteinase 10 (ADAM10) is a zinc dependent proteinase related to matrix metalloproteinases. ADAM10 has emerged as a key regulator of cellular processes by cleaving and shedding extracellular domains of multiple transmembrane receptors and ligands. In particular, ADAM10 has been identified as a key regulator of lymphocyte development. Here we report that ADAM10 is dispensable for early B cell development within the bone marrow. However, deletion of ADAM10 from all peripheral B cells or in post-switch cells leads to severe …


Predictors Of Carbapenem Resistant Gram-Negative Bacteria In A Consortium Of Academic Medical Center Hospitals, Mera Ababneh Jan 2012

Predictors Of Carbapenem Resistant Gram-Negative Bacteria In A Consortium Of Academic Medical Center Hospitals, Mera Ababneh

Theses and Dissertations

Background: Gram-negative resistance is a growing problem worldwide. It is generally believed that rates of resistant bacteria within a hospital are a function of antibiotic use, resistant organisms brought into the hospital, infection control efforts, and underlying severity of patient illness. The relative contribution of each to a particular resistance phenotype is unclear. P. aeruginosa is responsible for many hospital acquired infections and it may become resistant to carbapenems. In addition, newer threats to the future utility of the carbapenems are carbapenemase-producing K. pneumoniae Purpose: To determine if there is an association between the volume and composition of antibiotic use, …


Circuit Development In The Dorsal Lateral Geniculate Nucleus (Dlgn) Of The Mouse., Tania Seabrook Jan 2012

Circuit Development In The Dorsal Lateral Geniculate Nucleus (Dlgn) Of The Mouse., Tania Seabrook

Theses and Dissertations

The visual system is one of the most widely used and best understood sensory systems and the dorsal lateral geniculate nucleus (dLGN) of the mouse has emerged as a model for investigating the cellular and molecular mechanisms underlying the development and activity-dependent refinement of sensory connections. Thalamic organization is highly conserved throughout species and the dLGN of the mouse possesses many features common to higher mammals, such as carnivores and primates. Two general classes of neuron are present within the dLGN, thalamocortical relay cells and interneurons, both of which receive direct retinal input. Axons of relay cells exit dLGN and …


Cns Neural/Glial Progenitors As Targets Of Hiv-1 And Opiates: Effects On Proliferation And Population Dynamics May Alter Behavior Outcomes., Yun Kyung Hahn Jan 2012

Cns Neural/Glial Progenitors As Targets Of Hiv-1 And Opiates: Effects On Proliferation And Population Dynamics May Alter Behavior Outcomes., Yun Kyung Hahn

Theses and Dissertations

Human immunodeficiency virus (HIV) infected patients with a history of injection opiate abuse have higher incidences of acquired immunodeficiency syndrome (AIDS) and neurological dysfunction. The use of combined anti-retroviral therapy has significantly reduced the prevalence of mortality and progression to AIDS. Due to extended life expectancy, these patients are still at a great risk for HIV-associated neurological disorders and impairment in their later life. Neural progenitor cells (NPCs) play critical roles in brain growth and repair after injury and insult. Pediatric HIV patients whose glial populations are still developing are especially at risk for central nervous system (CNS) damage. Our …


Targeting The Endocannabinoid System To Reduce Inflammatory Pain, Sudeshna Ghosh Jan 2012

Targeting The Endocannabinoid System To Reduce Inflammatory Pain, Sudeshna Ghosh

Theses and Dissertations

The endogenous cannabinoids (endocannabinoids) anandamide (AEA) and 2-arachidonylglycerol (2-AG) exert their effects predominantly through cannabinoid CB1 and CB2 receptors, but these actions are short-lived because of rapid hydrolysis by fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), respectively. Selective inhibition of either enzyme elevates CNS levels of the appropriate endocannabinoid and produces analgesic effects with fewer psychomimetic side effects than Δ9-tetrahydrocannabinol (THC), the primary active constituent of marijuana. While cannabinoid receptor agonists and FAAH inhibitors reliably produce anti-inflammatory and anti-hyperalgesic effects in the carrageenan test and other inflammatory pain models, much less is known about the consequences of inhibiting …


Group I Metabotropic Glutamate Receptors On Selective Cellular Subtypes In Epileptogenic Malformed Cortex, William Bruch Jan 2012

Group I Metabotropic Glutamate Receptors On Selective Cellular Subtypes In Epileptogenic Malformed Cortex, William Bruch

Theses and Dissertations

Cortical malformations from altered development are common causes of human epilepsy. The cellular mechanisms responsible for the epileptic state of cortex remain unclear and a significant portion of these cases do not respond to treatment. Previous electrophysiological recordings in the Jacobs lab in a rat polymicrogyria model indicated an increased response to group I metabotropic glutamate receptor agonists in the region adjacent to the malformation (PMZ). In addition there was a novel response in low threshold spiking (LTS) interneurons via mGluR5 activation. To determine whether cell specific expression of these receptors was altered in malformed cortex immunohistochemical stains were performed …


Artemis And Metnase Mediated Processing Of 3΄-Blocked Dna Lesions: Role In Radio/Chemoresistance And Dna Repair, Susovan Mohapatra Jan 2012

Artemis And Metnase Mediated Processing Of 3΄-Blocked Dna Lesions: Role In Radio/Chemoresistance And Dna Repair, Susovan Mohapatra

Theses and Dissertations

DNA double-strand breaks (DSB) with chemically modified end-termini are the most significant lesions resulting from radio/chemotherapeutic intervention of cancer and non homologous end-joining (NHEJ) factor Artemis nuclease has been implicated in the repair of such breaks. To examine whether the resolution of terminally blocked DNA DSBs is the biologically relevant function of Artemis, Artemis deficient fibroblasts were stably complemented with wild type or an endonuclease deficient D165N mutant Artemis. Physiological levels of wild type (WT) Artemis completely restored DSB repair proficiency and resistance to γ-radiation, bleomycin, and neocarzinostatin. Cells expressing the D165N mutants remained as chemo/radiosensitive and as repair deficient …


Investigating The Role Of Α6 And Α4 Containing Neuronal Nicotinic Acetylcholine Receptors In Nicotine And Cocaine Conditioned Place Preference Tests In Mice., Sarah Sanjakdar Jan 2012

Investigating The Role Of Α6 And Α4 Containing Neuronal Nicotinic Acetylcholine Receptors In Nicotine And Cocaine Conditioned Place Preference Tests In Mice., Sarah Sanjakdar

Theses and Dissertations

Neuronal nicotinic acetylcholine receptors modulate both cholinergic and non-cholinergic synaptic transmission. Our research concerns α6 and α4 neuronal nicotinic subunits because they often co-assemble with the β2 subunit, which has abundant expression in the CNS and previous work has demonstrated that β2* nAChRs are involved in nicotine and cocaine reward. α6β2* and α4β2* nAChRs are highly expressed in midbrain, which is known to be critical for the incentive salience associated with natural and artificial (drug) reward. Our goal was to assess the role of α6β2* and α4β2* nAChRs in nicotine and cocaine reward using an unbiased conditioned place preference (CPP) …


The Role Of High Affinity Nicotinic Acetylcholine Receptors On Anxiety-Like Behavior: A Study In Female Mice, Jessicka Hall Jan 2012

The Role Of High Affinity Nicotinic Acetylcholine Receptors On Anxiety-Like Behavior: A Study In Female Mice, Jessicka Hall

Theses and Dissertations

Tobacco dependence is high in women who suffer from anxiety disorders yet little is known about the contributions of nicotinic acetylcholine receptors (nAChRs) on anxiety-like behavior. β2*nAChRs (*denotes assembly with other subunits) are the most abundantly expressed nAChRs in the brain yet little is known about the contributions of β2*nAChRs on anxiety-like behavior in female mice. In this study, antagonism and nicotine effects on anxiety-like behavior was investigated across the life span in 6, 12 and 24-month-old drug-naïve knockout (KO), heterozygous (HET) and a gain of function α6L9S mice and wild type (WT). HET mice showed increased sensitivity to di-hydrobeta-erythroidine …


Role Of Extracytoplasmic Function Sigma Factors In Porphyromonas Gingivalis, Suhasini Yanamandra Sai Jan 2012

Role Of Extracytoplasmic Function Sigma Factors In Porphyromonas Gingivalis, Suhasini Yanamandra Sai

Theses and Dissertations

Porphyromonas gingivalis is a major etiological agent that is responsible for the cause and progression of periodontal diseases. The bacterium is exposed to various environmental conditions and oxidative stress conditions while it is in the oral cavity. So, P. gingivalis should have an efficient regulatory system in order to adjust and survive in the oral cavity. But little is known about the regulatory mechanisms that help the bacteria to survive in the oral cavity. So, it is essential to understand and characterize these regulatory mechanisms. The response and adaptation of P. gingivalis to environmental stress conditions occur at the level …


Effectiveness Of Sensory Integration And Behavioral Interventions On Nonengagement In Preschool Aged Children, Tiffany Kuyper Jan 2012

Effectiveness Of Sensory Integration And Behavioral Interventions On Nonengagement In Preschool Aged Children, Tiffany Kuyper

Theses and Dissertations

Abstract EFFECTIVENESS OF SENSORY INTEGRATION AND BEHAVIORAL INTERVENTIONS ON NONENGAGEMENT IN PRESCHOOL AGED CHILDREN By Tiffany Ann Kuyper, OTR/L A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science in Occupational Therapy at Virginia Commonwealth University Virginia Commonwealth University, 2012 Director: Marie Anzalone ScD, OTR, FAOTA This single subject pilot study explored a combination of sensory-based interventions and behavioral interventions in a preschool aged child identified with Sensory Over-Responsivity (SOR). Children often display nonengagement associated with escaping and avoiding tactile and/or vestibular information because they perceive sensory input as negative or aversive. The subject …


Factors Influencing Pharmacists’ Decision To Report Adverse Events Related To Dietary Supplements, Ali M. Alhammad Jan 2012

Factors Influencing Pharmacists’ Decision To Report Adverse Events Related To Dietary Supplements, Ali M. Alhammad

Theses and Dissertations

Background: The increasing consumption of dietary supplements (DS) has drawn the attention of regulatory agencies, researchers and healthcare professionals. The US Food and Drug Administration (FDA) does not require premarketing assessment of DS considering them safe unless proven otherwise. However, the reporting rate of DS adverse events (DS-AE) is low. Objective: To describe pharmacists’ attitudes and knowledge of DS and DS information resources, and to determine the importance of selected attributes in pharmacists’ decisions to report a DS-AE. Methods: A convenience sample of practicing pharmacists in Virginia was surveyed using a web-based self-administered questionnaire. A conjoint analysis exercise was developed …


Designing Direct And Indirect Factor Xa Inhibitors, Rami Al-Horani Jan 2012

Designing Direct And Indirect Factor Xa Inhibitors, Rami Al-Horani

Theses and Dissertations

Anticoagulants are the basis for treatment and prevention of thrombotic diseases. The currently available medicines are associated with a wide range of adverse reactions that mandates developing new anticoagulants. Several lines of evidence support the superiority of factor Xa (FXa) as a promising target to develop novel anticoagulants. This work focuses on the design of direct and indirect FXa inhibitors using an interdisciplinary approach. As indirect FXa inhibitors, a focused library of tetrasulfated N–arylacyl tetrahydroisoquinoline (THIQ) nonsaccharide allosteric antithrombin activators was designed, synthesized, and biochemically evaluated to establish their structure–activity relationship (SAR). An N–arylacyl THIQ analog having carboxylate at position–3, …


A Comparison Of Maximal Exercise Responses Among Patients With A Total Artificial Heart, A Left Ventricular Assist Device, Or Advanced Heart Failure, Justin M. Canada Jan 2012

A Comparison Of Maximal Exercise Responses Among Patients With A Total Artificial Heart, A Left Ventricular Assist Device, Or Advanced Heart Failure, Justin M. Canada

Theses and Dissertations

The purpose of this study was to evaluate graded exercise responses to treadmill exercise in patients with a total artificial heat (SynCardia, Tucson, AZ). Additionally, this study sought to compare the exercise response in total artificial heart (TAH) patients to both advanced heart failure (HF) patients on medical management only and HeartMate II (Thoratec Corp., Pleasanton, CA) left‐ventricular assist device (HMII) patients. For patients with biventricular heart failure the TAH is a viable option to bridge patients until transplant becomes available. Its demonstrated improvement in mortality and increasing usage necessitates a shift in focus to quality of life in the …