Browsing by Subject "Other Pharmacy and Pharmaceutical Sciences"
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Item A Phase II Clinical Study to Evaluate the Efficacy and Safety of rhThrombin in Subjects Undergoing Arterial Bypass Surgery and AV Graft Formation for Hemodialysis(2004-12-01) Plascencia, Xochitl; Rustin E. Reeves; Della Weis; Don PeskaThe Association of American Medical Colleges Task Force on Clinical Research defines clinical research as a component of medical and health research intended to produce knowledge essential for understanding human disease, preventing and treating illness, and promoting health (Friedman, 1998). A clinical trial is defined as a research study conducted in humans which is designed to answer specific questions using scientifically controlled conditions with specified methodologies and endpoints (Gallin, 2002). Clinical research trials are essential in determining whether or not a drug is safe and effective. There are four phases that investigational drugs go through before they are allowed to be out in the market. Before beginning phase I of a study, there is usually a pre-clinical research and development phase. During this time the initial synthesis of study drug is accomplished and animal testing takes place. Phase I is the initial introduction of an investigational new study drug into humans. Phase I is usually conducted in healthy individuals and the primary goal is to determine the safety profile of the drug. Phase II trials tend to evaluate safety and initial efficacy. Subjects enrolled in this phase tend to have the disease necessary for use of study drug. Phase III studies are conducted to gather additional information about the effectiveness and safety of the drug and to determine the overall benefit-risk relationship of the drug. Finally, phase IV studies are usually referred to as post-marketing studies. During this phase, additional safety information is identified and the drug’s safety during routine use is evaluated. Each phase can range from two to ten years depending on the complexity of the clinical trial (Gallin, 2002). A phase II, randomized, double blind study of the safety and efficacy of topical recombinant human thrombin in patients undergoing peripheral arterial bypass surgery and arterio-venous graft formation for hemodialysis is the focus of the prospective drug study to be carried out in the surgery department at The University of North Texas Health Science Center. The primary objective of this study is to evaluate the safety and efficacy of recombinant human thrombin when used in different types of surgeries. Prior to signing an informed consent, subjects will have to meet inclusion and exclusion criteria set by study protocol. Study specific assessments and procedures will be performed after the informed consent is signed and dated. If bleeding at the anastomosis is found to necessitate intervention, a single application of either rhThrombin or placebo in combination with an absorbable hemostatic sponge to each anastomosis requiring hemostasis will be applied by the surgeon. The safety and efficacy of rhThrombin will be determined by measuring the incidence and severity of adverse events and of laboratory abnormalities. Occurrence of hemostasis within 600 seconds of application of the study drug at the anastomotic surgical site, incidence of anti-rhThrombin product antibodies, and time to hemostasis will also be measured.Item A Study of the Effectiveness and Tolerability of Weekly Rifapentine/Isoniazid for Three Months Versus Daily Isoniazid for Nine Months for the Treatment of Latent Tuberculosis Infection(2004-11-01) Lemp, Jessie; Patricia Gwirtz; Walter McConathy; Richard EasomLemp, Jessie M. A Study of the Effectiveness and Tolerability of Weekly Rifapentine/Isoniazid for Three Months Versus Daily Isoniazid for Nine Months for the Treatment of Latent Tuberculosis Infection. Master of Science, November, 2004, 107 pp., 4 tables, 4 figures, references, 29 titles. The standard treatment for latent tuberculosis infection, nine months of daily isoniazid, is effective at preventing active tuberculosis; however, its full benefits are limited by non-adherence. A shorter intermittent regimen of rifapentine plus isoniazid once weekly for three months is equally effective as the standard regimen in animal models. This regimen facilitates the use of directly observed therapy, a method that significantly improves adherence. The Center for Disease Control is sponsoring Study 26 to test the effectiveness and tolerability the three-month rifapentine based regimen in latently infected persons with risk factors for progression to active tuberculosis. This thesis will describe the background rationale and methods for the clinical trial, and the internship experience.Item Analysis of the Clinical Research Methodologies Employed During a Phrase Three Efficacy Study for Ultracet as a Post-Herniorrhaphy Analgesic(2001-08-01) Aguilar-Zanatta, Jorge; Rustin Reeves; Don Peska; Della WeisThe history of pain management stems back many thousands of years. However, not until recent times have significant advancements in biochemistry and pharmacology allowed analgesics to be incorporated in clinical interventions and everyday life. Due to these advancement, attempts to refine pharmacological action on receptors in terms of specificity would render medications with fewer side effects. The technology is present, but the application and development of modern analgesics in post-surgical settings is substandard. According to C.L. Ireson and R.W. Schwartz, (2001), the outcomes of ailment interventions in the United States are “…no better and in numerous situations worse that those achieved in other countries,” even though the United States has the most expensive healthcare in the world. Furthermore, a study performed by Carr et al. (1998), has identified the United States as demonstrating consistent inadequacies in postoperative pain management. Several factors have been identified as being contributors of poor post-surgical pain control in America. Lack of awareness of the available strategies in acute pain control and its implementation in post surgical care are labeled as being problematic observations (Puid et al., 2001). In response to these conditions as well as the managed health care time and cost limitations, new and efficacious pharmaceuticals must be made available to a broad spectrum of socio-economic strata. Currently, there is a great debate over the use of laparoscopic herniorrhaphy versus open tension free approaches. In terms of cost, the laparoscopic herniorrhaphy versus open tension free approaches. In terms of cost, the laparoscopic herniorrhaphy versus open tension free approaches. In terms of cost, the laparoscopic procedure is more expensive and yields less postoperative pain, however the open tension free approaches are less expensive and yield more postoperative pain (Sarli et al., 2001, Medical Research Council Laparoscopic Groin Hernia Trial Group, 2001, Parviz et al., 1995). There are advantages and disadvantages to both procedures. Assuming that efficacious postoperative analgesics were available, the open tension free repair would be more feasible in terms of cost and hernia recurrence rates (Sarli et al., 2001). In terms of pharmaceutical development, the laws and guidelines by the regulatory agencies such as the Food and Drug Administration, institutional review boards, and pharmaceutical sponsor protocols must be followed. Along with good clinical practice standards, interdisciplinary collaboration in pain studies produce results that are statistically and clinically salient. The patient’s well-being and comfort is the ultimate goal in clinical pain studies and in medicine in general, therefore postoperative pain should be aggressively managed.Item Analyzing the Scientific Debate of Coxibs and The Ethics Impact of Vioxx's Withdrawal on Drug Regulation and an Ongoing Phase III Clinical Trial with a New Cox-2 Inhibitor(2005-11-01) Fu, Jingwei; Gwirtz, Patricia A.; Rubin, Bernard R.; Jiminez-Williams, CynthiaOn September 30, 2004, Merck & Co. Inc announced voluntary withdrawal of its $25 billion blockbuster drug Vioxx from the market, five and a half years after Voixx received FDA approval. This is the largest prescription drug withdrawal in history. Merck made the decision based on the results of APPROVe (Adenomaous Polyp Prevention on Vioxx) clinical trial, which showed that Voixx had an increased risk of myocardial infarction and cerebral vascular stoke compared with placebo. The repercussions of Merck’s action were tremendous from both a financial aspect and an ethical aspect. The recalling of Vioxx has become an important public health issue and has placed drug regulation agencies in controversy. In April, 2005, Pfizer agreed to voluntarily suspend sales and marketing of its COX-2 inhibitor, Bextra in the United States as requested by the FDA. Vioxx and Bextra withdrawal has left a huge impact on the pharmaceutical industry. Debates are ongoing in the scientific community regarding the use of Cox-2 inhibitors and have caused much confusion in the medical community and in those who use these drugs for pain control for osteo- and rheumatoid arthritis disease. The goal of this report is to analyze the impact of Vioxx withdrawal and comment on how to apply this incident in guiding the industry with regards to drug development, drug regulation, and clinical practice in order to ensure the effectiveness in the drug development and safe usage of new pharmaceutical agents.Item Cardiac Parasympathetic Dysfunction in Morphine Addiction(1997-12-01) Napier, Leslie D.; Caffrey, James L.; Raven, Peter B.; Gwirtz, Patricia A.Napier, Leslie D., Cardiac Parasympathetic Dysfunction in Morphine Addiction. Doctor of Philosophy (Biomedical Sciences), December, 1997, 137 pp., 9 tables, 22 figures, references, 163 titles. The effects of chronic morphine treatment on parasympathetic control of the heart and associated cellular mechanisms were examined using a canine model. Vagal bradycardia was significantly blunted in dogs treated for one week with subcutaneous morphine pellets. In a separate group of dogs, heart rate and high frequency fluctuations in heart rate declined during the first three hours of subcutaneous morphine infusion consistent with the vagatonic action of acute morphine. Heart rate remained below baseline on Day 2 of the morphine infusion but had returned to normal by Day 10. Ambient sympathetic tone was increased on Days 2 and 10, and plasma catecholamines were elevated on Day 2. The intrinsic heart rates on Days 2 (160 bpm) and 10 (162 bpm) of morphine treatment were lower than the pre-treatment rate (182 bpm). Suggested mechanisms include a fundamental change in sinoatrial nodal cell function or attenuated tachycardia induced by vasoactive intestinal peptide co-released with acetylcholine from post-ganglionic parasympathetic neurons. The time to 50% maximal bradycardia during vagal nerve stimulation was increased with chronic and acute morphine suggesting an effect on the rate of acetylcholine synthesis, release or degradation. Muscarinic receptor density in left ventricular and right atrial sarcolemmal membranes from dogs treated chronically with morphine were 34% and 17% higher, respectively, than in control animals. Chronic morphine had no effect on basal or MnCl2-stimulated cyclase activity in either region. Similarly, maximal β-adrenergic and muscarinic receptor/G-protein coupling to adenylate cyclase were not altered by chronic morphine. Atrial norepinephrine content was higher than that in the ventricles and was unaltered by morphine. Ventricular norepinephrine was decreased with chronic but not acute morphine treatment. Epinephrine was evenly distributed throughout the myocardium and was reduced in both the atria and the ventricles by either acute or chronic morphine. This pattern suggests that morphine may reduce extraneuronal uptake of catecholamines. Collectively these studies show that chronic morphine treatment and the accompanying persistent vagal activity may reduce parasympathetic function. This attenuated function, however, is short-lived since sympathetic systems adapt with compensatory responses masking, or perhaps reversing, initial parasympathetic deficits.Item Characterization of Protein Kinase C in Cisplatin Sensitive and Resistant Human Cervical Cancer HeLa Cells(2000-12-01) Mohanty, Sanghamitra; Basu, Alakananda; Simecka, Jerry; Dimitrijevich, DanMohanty, S., Characterization of protein kinase C in cisplatin sensitive and resistant human cervical cancer HeLa cells. Master of Science (Microbiology and Immunology), December, 2000. 37 pp., 11 illustrations, bibliography, 27 titles. Signal transduction plays a crucial role in carcinogenesis. A defect in signaling, by evading cell death or promoting cell proliferation, may result in neoplastic transformation or protection of cells from the cytotoxicity of anticancer drugs. Therefore, in order to understand the complex mechanism of drug resistance, it is relevant to probe into the important signal transduction pathways. Protein kinase C, a key signal transducer, influences cisplatin sensitivity in many cell lines. We examined whether or not the PKC signal transduction pathway is affected during development of resistance to cisplatin by tumor cells. PKC activators increased cisplatin sensitivity in both parental and cisplatin-resistant cells. Western blot analysis showed a slight decrease in cPKCα and nPKCε, an evaluation in nPKCδ and no change in the abundance of PKCϚ in HeLa/CP cells compared to HeLa cells. Though TPA-induced translocation of PKC isoforms was identical in both cell lines, down regulation of PKCδ was defective in resistant cells. Therefore, a deregulation in PKCδ was associated with cisplatin resistance.Item Clinical Internship with the Division of Gynecologic Oncology at UT Southwestern Medical Center: Carboplatin and Doxil for Gynecologic Cancers(2003-12-01) Epps, Camitria N.; Victoria Rudick; David S. Miller; Barbara RichardsonEpps, Camitria N., Master of Science, Clinical Research Management, December 2003, Carboplatin and Doxil for Gynecologic Cancers, 107 Pages, 9 Tables, 42 titles in Bibliography. Objective: To examine the safety and efficacy of administering the drugs carboplatin and doxil in combination chemotherapy for the treatment of gynecologic cancers, mainly endometrial and ovarian cancer. Materials and Methods: Carboplatin and doxil were previously administered intravenously to 6 patients. Each patient received 3 to 8 cycles of chemotherapy. Doses of carboplatin ranged from 310 mg to 665 mg. The doses of doxil ranged from 54 mg to 80 mg. This is a retrospective study. The 6 patient’s medical charts were reviewed. Data was extracted and a spreadsheet formatted database was created. Results: Data were extracted and a spreadsheet formatted database was created. Results: Due to the small number of patients the results are not statistically significant. 2 patients showed tumor progression while receiving treatment. All patients tolerated doses very well and experienced minimal toxicities. Conclusion: Carboplatin plus doxil combination chemotherapy given intravenously has a potent effect on endometrial and ovarian cancers. Studies using this chemotherapy for the treatment of gynecologic cancers should be conducted on a wider scale to access the statistical significance of the treatment.Item Clinical Internship with the Pediatric Clinic's Clinical Research at the Patient Care Center of the University of North Texas Health Science Center/Texas College of Osteopathic Medicine: Literature Review of Meningococcal Meningitis(2002-07-01) Puckett, Fredric Clark; Harold Sheedlo; Robin Newman; John FlingEpidemic meningococcal meningitis and meningococcemia disease is caused by the bacterial pathogen Neisseria meningitidis. Once infected with meningococci, onset of the disease is rapid with a high rate or morbidity and mortality. Without medical intervention the mortality rate is over 50%. Medical treatment is over 50%. Medical treatment of an outbreak of the disease with antibiotics can reduce the death rate to 10-15%. However, 10-20% of survivors will suffer from neurological damage that may include loss of hearing, paralysis or mental retardation. Recent concerns have been noted regarding the emergence of Neisseria meningitidis strains resistant to antibiotics. Vaccines have been developed in an effort to reduce epidemic outbreaks of meningococcal meningitis and meningococcemia. The first generation polysaccharide vaccines have shown to be safe and possess some degree of effectiveness but have shortcomings of limited length of immune protection and evidence of hyporesponsiveness to subsequent vaccinations. The second generation conjugated polysaccharide vaccines have been able to overcome these problems and show great promise in reducing the sale of epidemic meningococcal outbreaks with implementation of effective mass vaccination campaigns. In addition, reducing the number of infections will limit the exposure of Neisseria meningitidis to antibiotics and, in theory, slow the development of resistance to antibiotics.Item Clinical Research: Drug Studies and Device Trials, Theory and Approach(2002-07-01) McCormick, Timothy Chad; Rustin Reeves; Don Pesca; Dellas WeisA clinical trial is composed of four different phases. Each of these phases serve a purpose such as testing safety, efficacy, and dosage. These phases are essential to provide the best possible model for mass use of a drug or a new device. Drug studies differ from device studies in their design and their delivery. In this case, a post-operative pain medication was tested, as well as a differential study between two types of cutting devices used in laparoscopic cholecystectomy. The post-operative pain study is a phase III study that is testing the efficacy, safety, and the pharmacokinetics of a proposed drug. The device study is considered a phase IV study because it is evaluating two commonly used techniques for laparoscopic cholecystectomy. Both of these techniques have previously been approved by the FDA and are mass marketed. These two studies were followed for six weeks and evaluated for protocol design, differences and similarities, and for hands on experience in the clinical research arena. Upon completion of the six week opportunity, it is evident that clinical research is a viable piece of medicine today. Following these two studies allowed for an understanding of the differences and similarities encountered when executing a drug study, as well as a device study. The complexities of the two studies were evaluated, and without doubt, the drug study included much more paper work, patient testing, inclusion/exclusion criteria, study evaluation, and most of all, man hours. All in all, this was a very rewarding experience that allowed for a greater understanding of the implementation and value of today’s clinical research.Item Combined Chemo/Anti-Angiogenic Cancer Therapy in Lewis Lung Metastases(2002-05-01) Sinha-Datta, Anjuli; Goldfarb, Ronald H.; Agarwal, Neeraj; Mathew, Porunelloor A.Datta, Anjuli. Combined Chemo/Anti-Angiogenic Cancer Therapy in Lewis Lung Metastases. Master of Science (Microbiology and Immunology), May 2002. 41 pp., 17 illustrations, bibliography. The focus of my dissertation studies is an eight amino acid peptide (Å6) derived from the non-receptor binding region of urokinase plasminogen activator (uPA), which partially inhibits the binding of uPA to its receptor (uPAR). Å6 has been synthesized as a potential novel anti-cancer agent and kindly provided by Ångstrom Pharmaceuticals, Inc. (San Diego, CA). We further examined potential therapeutic properties of Å6 in vivo and in vitro. Å6 appeared to directly inhibit the invasion of Lewis lung carcinoma cells through Matrigel by approximately 40-45% compared to control. In addition, Å6 had a morphological effect resulting in thicker tubes on small vessel endothelial tube formation compared to no treatment. Interestingly, doxorubicin had similar effects when added to growing endothelial cells. Moreover, Å6 was administered alone and in combination with a standard clinically used chemotherapeutic agent, doxorubicin, in a Lewis lung carcinoma mouse model to test possible synergy between an anti-angiogenic compound (Å6) and a chemotherapeutic agent. This is the first observation that Å6 has the potential to display a direct anti-metastatic therapeutic effect for established pulmonary metastases in this model. Therefore, we believe that Å6 in combination with doxorubicin has the potential to provide better therapy to cancer patients with tumor metastases than potent chemotherapeutics agents alone, by increasing the dose of non-toxic Å6 and reducing the recommended dose of doxorubicin.Item Cross-Tolerance Between the Discriminative Stimulus Properties of Ethanol, Diazepam and Pentobarbital(1995-12-01) Lytle, Douglas A.; Michael Forster; Glenn Dillon; Thomas YorioLytle, Douglas A., Cross-Tolerance Between the Discriminative Stimulus Properties of Ethanol, Diazepam and Pentobarbital. Doctor of Philosophy (Biomedical Sciences), December, 1995, 132 pp., 8 tables, 19 figures, bibliography, 176 titles. Ethanol, benzodiazepine agonists and barbiturates all facilitate GABA-mediated CT flux. The present experiments tested the hypothesis that, because these agents share this common action, tolerance to discriminative stimulus properties of one of these drugs would result in cross-tolerance to the others. Rats were trained to detect either ethanol (EtOH; 1.0 g/kg), the benzodiazepine diazepam, (DZP; 5.6 mg/kg), or the barbiturate pentobarbital (PB; 10.0 mg/kg) from vehicle using a two-lever choice procedure where food was available under a fixed-ration ten schedule of reinforcement. Subsequently, dose-effect curves for EtOH (0.1-1.78 g/kg), DZP (0.56-17.8 mg/kg), or PB (1.0-17.8 mg/kg) were tested before and after chronic administration of EtOH 96.0 g/kg/12hrs for seven days), DZP (20.0 mg/kg/8hrs for seven days), or PB (32.0 mg/kg/8hrs for seven days). The chronic administration of EtOH conferred tolerance to itself in all cases and cross-tolerance to DZP and PB in subjects trained to detect EtOH, but did not confer cross-tolerance to these agents in their respective discriminations. The chronic administration of DZP conferred tolerance to itself substituting for DZP. Although tolerance developed to DZP substituting for PB after treating animals with chronic DZP, this regimen on DZP did not confer tolerance to itself substituting for EtOH. This regimen of DZP failed to confer significant cross-tolerance to either EtOH or PB under any conditions. The chronic administration of PB conferred tolerance to itself substituting for PB. Although tolerance developed to PB substituting for DZP after treating animals with chronic PB, this regimen of PB did not confer tolerance to itself substituting for EtOH. This regimen of PB failed to confer significant cross-tolerance to either EtOH or DZP under any conditions. In summary, EtOH was found to confer cross-tolerance to DZP and PB only in animals trained to detect EtOH. The chronic administrations of DZP and PB failed to confer tolerance to themselves substituting for EtOH. These results are parsimonious with the heterogeneous nature of the GABA receptor. Finally, tolerance to either DZP or PB does not result in cross-tolerance to the discriminative stimulus properties of the other drug. These results suggest that the mechanisms mediating tolerance to BZs and barbiturates are not linked.Item Establishing Metrics for Evaluating Performance and Quality in Clinical Trial Management(2012-12-01) Vandermause, Matthew C.; Rustin ReevesPurpose: To identify performance metrics for use in clinical trial management, identify different levels of understanding of and experience with performance metrics among clinical research professional, and to establish performance metrics within the clinical research organization MedTrials, Inc. Hypothesis: There is a significant gap in knowledge and disconnect between clinical research professionals regarding performance metrics and how and when to use them. Design: A survey was designed to test the understanding and knowledge of clinical research professionals regarding performance metrics. This study survey was also designed to gather opinions of clinical research professionals regarding the usefulness of performance metrics and when and where to appropriately use performance metrics. Results: There is a deficiency in the understanding of performance metrics among clinical research professionals, as well as some disconnect regarding how to appropriately use performance metrics.Item Horse Serum High Density Lipoproteins as Drug Transporters(2004-05-01) Johnson, Shemedia; Walter McConathyJohnson, Shemedia J., Horse Serum High Density Lipoproteins (HDL) as Drug Transporters. High-density lipoproteins (HDL) are complex particles composed of specific proteins and lipids that facilitate blood and tissue cholesterol homeostasis by transporting excess peripheral cholesterol to the liver. In association with cholesterol ester transfer protein (CETP) and the enzyme, lecithin: cholesterol acyltransferase (LCAT), HDL contributes to the transport of hydrophobic lipids, including cholesterol ester and triglycerides through the blood. The studies presented here involve the evaluation of horse serum HDL as a carrier of water insoluble drugs and an improved process to isolate and purify horse serum HDL utilizing hydrophobic affinity chromatography. Dilauryl fluorescein (DLF) has been chosen as a model compound for the study of horse HDL as a drug carrier. The prepared HDL/DLF particles have similar flotation densities and size properties to native horse serum HDL. The amount of DLF incorporated into HDL is 30μg/mg protein. Various cancer cell lines internalized DLF from horse HDL/DLF particles successfully. While human plasma contains cholesterol ester transfer protein (CETP), horse plasma does not. Horse plasma/serum can be supplemented by human plasma to study the role of CETP in drug transport and the stability of the horse HDL/drug complex.Item Lifelong vs. Late Life Tocopherol on Learning and Memory in Mice(2004-05-01) McDonald, Shelley R.; Michael Forster; Glenn DillonMcDonald, Shelley R., Lifelong vs. late life tocopherol on learning and memory in mice. Doctor of Philosophy (Biomedical Sciences), May, 2004, 132 pp., 1 table, 14 figures, bibliography, 122 titles. The purpose of these studies was to determine if vitamin E supplementation, a well-studied antioxidant, could improve the cognitive functions of old mice either by preventing age-dependent impairments or reversing age-related dysfunction. Cellular oxidative stress is believed to be a causal factor in senescence, and the brain appears to be particularly susceptible to oxidative damage because of a relatively high rate of reactive oxygen species generation without commensurate levels of antioxidant defenses. If oxidative stress indeed plays a role in age-related brain dysfunction, then it can be predicted that experimental interventions capable of lowering oxidative stress would either prevent or restore function. This was tested using apolipoprotein E-deficient mice, which have an increased susceptibility to neuronal oxidative damage, maintained on 3 different doses (2 mg/kg, 20 mg/kg, or 200 mg/kg/day) of dl-α-tocopheryl acetate (vitamin E) via supplemented food pellets from 8 weeks of age throughout behavioral testing when 6 or 18 mo of age. A separate experiment used wild type mice 24 months of age to examine whether or not a combination of vitamin E (123 mg/kg/day) with coenzyme Q10 (200 mg/kg/day) which leads to higher tissue levels of vitamin E, could improve brain functions in old mice. Mice were tested on multiple behavioral tasks that required utilization of various components of memory and learning, as well as sensorimotor testing. The highest dose of vitamin E prevented the decline of spatial memory in old apolipoprotein E-deficient mice, but did not prevent age-related impairments in learning and memory for discriminated escape. When old wild type mice were treated with the combined vitamin E and coenzyme W10, the mice learned and remembered to avoid a preemptive shock significantly more than old mice treated with vitamin E or coenzyme Q10 alone. A followup experiment with higher doses of coenzyme Q10 alone (250 or 500 mg/kg/day) resulted in no cognitive improvements. No treatments improved sensorimotor performance.Item Overview of Study Start Up Activities for a Clinical Trial at an Investigative Site(2012-11-01) Chaudhari, Prianka S.; Dr. Patricia GwirtzPracticum site, ACRC Trials is a Site Management Organization (SMO) which provides services to the sponsors and Contract Research Organizations (CROs). The main aim of the internship practicum was to describe, analyze and comprehend the study start up activities for a clinical trial at the practicum site. The aim was accomplished by administering survey questionnaire to the staff members, reading study start up Standard Operating Procedures (SOPs) and checklists. If an investigative site optimizes and develops the Standard Operating Procedures (SOPs) for a clinical trial irrespective of type and length of the study then significant time and money can be saved. Saved resources can be used to make an investigative site more efficient in conducting and managing multiple trials.Item Pharmacological Evaluation of the D2 and D3 Dopamine Receptor Selective Compounds on L-Dopa Dependent Abnormal Involuntary Movements in Rats(2008-05-01) Kumar, Rakesh; Robert Luedtke; Hriday K. Das; Nathalie SumienKumar Rakesh, Pharmacological Evaluation of the D2 and D3 Dopamine Receptor Selective Compounds on L-dopa Dependent Abnormal Involuntary Movements in Rats. Master of Science (Pharmacology & Neuroscience), May 2008, 106 pp, 21 illustrations, references, 31 titles. Parkinson’s Disease (PD) is a progressive, neurodegenerative disease of the dopamine neurons that innervate the striatum and is characterized by resting tremor, rigidity, bardykinesia and postural instability. L-dopa treatment is the most common and effective therapy for PD. However, both motor (wear-off phenomena, rigidity and dyskinesia) and non-motor (sweating, tachycardia, restless leg syndrome, anxiety, depression, confusion, reduced alertness, psychosis and/or dementia) side effects are associated with long term L-dopa therapy. Motor complications depend on the duration of L-dopa treatment and the abnormal involuntary movements are known as L-dopa-induced dyskinesia (LID). Several studies have suggested a possible role of the dopamine D3 receptor subtype in LID. Here I evaluated the effects of various D2 and D3 dopamine receptor selective compounds on LID in 6-hydroxydopamine-induced complete lesioned hemi-parkinsonian model of rat. D3 dopamine receptor selective compounds (agonists, partial agonists or antagonists) have antidyskinetic effects on LID. Co-administration of D3 dopamine receptor agonist and D3 dopamine receptor antagonist has additive effects in attenuating the LID instead of antagonizing the effects of each other in vivo. D3 dopamine receptor selective compounds attenuated apomorphine-induced dyskinesia.Item Presentation of a Sample Case Studies from a Phase 4 Clinical Trial, "Communit-Based Research Assessment Investigating Clobetasol Proplonate 0.05% Spray for the Treatment of Chronic Plaque Psorias - The COBRA Trial"(2008-03-01) Kulkarni, Gopal; Gwritz, Patricia A.; Colon, Luz E.; Johnson, Lori A.Internship Project. Title of the Project. Presentation of Sample Case Studies from phase 4 clinical trial, “Community-Based Research Assessment Investigating Clobetasol Propionate 0.05% Spray for the Treatment of Chronic Plaque Psoriasis- the COBRA trial” Specific Aims. The specific aims of the practicum were to: 1) Select 50 subjects who had photographs available from the Data Listing (database) of the COBRA trial subjects; 2) Collect data for each case from the database provided; 3) Classify the collected data into efficacy, safety, subject satisfaction, compliance and quality of life evaluations; 4) Generate a presentation (slide kit) of the selected case studies for educational and training purposes. Signficance. Case study presentations are a tool to demonstrate the performance of a drug used in a clinical trial. Due to the large scale of the COBRA trial, there was to a need to generate a reference presentation using data belonging to a sample of subjects from the trial. This reference presentation may be useful for educational and training purposes. This chapter describes the process of development of these case study presentations from the data obtained in the COBRA trial.Item Properties of a Human Metastatic Variant Lung Cancer Model(2003-05-01) Poirot, Julie E.; Mart Hart; Robert Wordinger; Rick KitsonPoirot, J. Properties of a Human Metastatic Variant Lung Cancer Model. Master of Science (Molecular Biology and Immunology). May 2003. 44 pp., 11 illustrations, 1 table, 39 bibliography titles. A model of non-small cell lung cancer (NSCLC) has been developed for screening and preclinical drug evaluation by implanting the A549 lung cancer cell line orthotopically into immunocompromised (SCID) mice. Aggressive metastatic sublines were then derived from metastases from the primary implant. The purpose of this project is to elucidate some of the cellular properties involved in the tumor aggressiveness of the metastatic variant cell lines. In vitro migration and invasion assays produced data showing no significant differences between the rates of migration or invasion of parental and metastatic sublines. In vivo tumor burden experiments, however, produced data showing significant differences in the numbers and sizes of metastatic tumors formed when the three cell lines were compared in SCID mice. RT-PCR analysis has indicated that there are differences in the mRNA levels of certain matrix metalloproteinases. The A549 parental cells have matrix metalloproteinase-2 (MMP-2) but not MMP-9, while both metastatic variants show MMP-9 mRNA but no MMP-2. Western blots and gelatin zymographies also confirm these findings. RT-PCR analysis and casein zymography experiments have also shown no differences in the message or activity of urokinase plasminogen activator *uPA0 among the cell lines. Multidrug resistance studies were done on the tumor cell lines in order to compare their resistance to various classes of antineoplastic drugs. These studies indicate that there is no significant difference in the resistance to doxorubicin or paclitaxel, but the parental cell line is substantially more resistant to cisplatin than either of the metastatic sublines.Item Review of the History of Coronary Stenting, Role and Evolution of Adjunctive Pharmacotherapy and Experience with an Ongoing Drug-Eluting Stent Trial(2005-12-01) Kang, Mi Jung; Bens, Annita V.; Ratka, Anna; Oglesby, MichaelKang, Mi Jung. Review of the History of Coronary Stenting, Role and Evolution of Adjunctive Pharmacotherapy and Experience with an Ongoing Drug-Eluting Stent Trial. Master of Science (Clinical Research Management), December 2005, 116 pp., 6 tables, 12 figures, bibliography, 61 titles. The history of stent development with regard to the use of coating materials and eluting drugs, with special emphasis on mechanism of release and duration of action of drugs used in drug-eluting stents, was summarized. The general safety profile of currently used adjunctive pharmacotherapy to coronary stenting, with special emphasis on the clinical trials providing the scientific assessments of the effectiveness and safety of the regimens was reviewed. The enrollment process and the critical role of the Clinical Research Coordinator (CDC) in the process of the implementation of a clinical study with a new drug-eluting stent were described.Item Safety and Efficacy of Alefacept, Efalizumab, Etanercept, and Infliximab in Treating Moderate to Severe Psoriasis: A Meta-Analysis of Randomized Controlled Trials(2007-05-03) Brimhall, Angela K.; John Licciardone; Roberto Cardarelli; Richard VirgilioBrimhall, Angela K., Master of Science, Clinical Research and Academic Medicine, May 19, 2007, Safety and Efficacy of Alefacept, Efalizumab, Etanercept, and Infliximab in Treating Moderate to Severe Plaque Psoriasis: A Meta-Analysis of Randomized Controlled Trials. Pages=41, Tables=3, Figures=9, Bibliography=61 titles. To evaluate and compare efficacy and safety of biological agents in the treatment of plaque psoriasis, data was identified through four parallel systematic reviews. Randomized, controlled, double-blind, monotherapy trials of alefacept, efalizumab, etanercept and infliximab were selected. Sixteen studies comprising 7,931 patients met inclusion criteria. Efficacy was measured by pooled relative risk (RR) and number needed to treat (NNT) of PASI 75 achievement as compared to placebo. Each biological agent was efficacious (P [less than] .001); however, there was a graded response for achievement of PASI 75. The risk of one or more adverse event was increased in the alefacept, efalizumab, and infliximab groups compared to placebo.