Browsing by Subject "Rheumatology"
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Item Safety and Efficacy of a Novel Xanthine Oxidase/Xanthine Dehydrogenase Inhibitor in the Treatment of Gout(2003-12-01) Brooks, Molly; Rudick, Victoria; Forman, Mitchell; Jimenez-Williams, CynthiaSummary: The internship report is based on the activities completed during the Internship Practicum at the Department of Internal Medicine, Division of Rheumatology, at the University of North Texas Health Science Center at Fort Worth and at the Rheumatology Clinic at John Peter Smith Hospital. This internship serves as partial training in the area of Clinical Research Management and focuses on studies involving rheumatic diseases, with specific emphasis on Gout. Specific Aims/Hypothesis: Ongoing clinical trials in the Department of Internal Medicine Rheumatology clinic are the bases for the project which focuses on the treatment of gout and a proprietary study on the uses of a novel xanthine oxidase/ xanthine dehydrogenase inhibitor (XOD/XDH inhibitor) to relieve the symptoms of gout. The particular research is a phase three study to assess the safety and efficacy of a novel xanthine oxidase/ xanthine dehydrogenase inhibitor compared to a placebo and an established xanthine oxidase/ xanthine dehydrogenase inhibitor, allopurinol. The hypothesis of the study is that the new XOD/XDH inhibitor will be more effective at lowering uric acid levels and thus will reduce the frequency of gout more effectively and with fewer side effects than traditional treatment or a placebo. Under the direction of the Department of Internal Medicine, subjects who met inclusion/exclusion criteria of the study were randomly assigned to be treated with colchicine in addition to either allopurinol, or the novel compound, which hereafter will be referred to as the novel XOD/XDH inhibitor, or to a placebo. The safety and efficacy of the novel XOD/XDH inhibitor will be compared to the traditional drug of choice allopurinol, a uric acid lowering agent, and to a placebo. The placebo is an inactive pill that is designed to look and taste like either allopurinol or the novel XOD/XDH inhibitor. While the period of the internship is not long enough to complete the study and thereby assess the reliability of the hypothesis, the internship and this report have two specific aims: (1) to perform a literature search of gout and related topics and (2) to understand and perform activities of a clinical research coordinator as they relate to the novel XOD/XDH inhibitor study and to other clinical trials in rheumatology. The literature search focuses on specific areas concerned with details about gout: history, epidemiology, forms, causes, signs and symptoms, clinical diagnosis, differential diagnosis, complications, therapeutics (past, present, and future), prevention, associations, cellular mechanisms involved in hyperuricemia, as well as inflammation. The project also provides a description of the activities involved in clinical research, and discusses specifically the roles of the various personnel: Clinical Trials Coordinator, Principle Investigator, Sub-investigator, Institutional Review Board, and Clinical Trials Monitor as they have been involved in the novel XOD/XDH inhibitor study and other studies in rheumatology. Significance: Finding a new treatment for gout is of significant importance for several reasons. In countries with a high standard of living, such as the United States, prevalence of gout has increased and is probably the second most common form of inflammatory arthritis. Gout can result in significant short-term disability, occupational limitations, and increased utilization of medical services therefore making the disease a significant public health problem. New treatment options could greatly improve the prognosis for patients and in addition reduce the cost of the disease by preventing loss of wages due to patient absence from work, for example. Furthermore, new treatments for gout could provide patients with safer therapeutics alternatives than the traditional treatments.Item The Roles of IFN-y and IL-4 in the Upper and Lower Respiratory Tracts Immune Responses Toward Mycoplasma Infection(2003-12-01) Woolard, Matthew D.; Jerry SimeckaWoolard, Matthew D., The Roles of IFN-γ and IL-4 in the Upper and Lower Respiratory Tracts Immune Responses Toward Mycoplasma Infection. Doctor of Philosophy (Biomedical Sciences), December, 2003, 136 pp., 1 table, 16 illustrations, bibliography, 152 titles. The purpose of these studies was to evaluate the roles of IFN-γ and IL-4 during the development of immune responses of the upper and lower respiratory tracts, during mycoplasma respiratory disease. To study their roles, we took advantage of IFN-γ and IL-4 knockout (KO) mice. The loss of IL-4 did not impact the development of disease or the clearance of mycoplasma from either respiratory tracts during mycoplasma infection. However, IL-4 mediated responses dampen mycoplasma induced bronchial hyperresponsiveness (BHR), which are in direct contrast to theories that state that IL-4 is critical for the development of BHR. This suggests that mycoplasma exacerbation of asthma is a synergism between IL-4 and non-IL-4 mediated responses. Thus, IL-4 does not impact mycoplasma disease development, but dampens detrimental non-IL-4 mediated responses that exacerbate BHR during mycoplasma disease. The loss of IFN-γ did not affect disease or the number of mycoplasma organisms in the upper respiratory tract; this is in contrast to the lungs where the loss of IFN-γ led to a defect in innate immune responses. A significant increase in mycoplasma organisms were seen by day 3 post-infection which led to exacerbation of disease pathology. By three days after infection, only the number of IFN-γ+ NK cells increase in numbers in response to mycoplasma infection. However, the depletion NK cells by anti-asialo GM1 antibody treatment did not affect the clearance of mycoplasma from lungs of BALB/c mice, however, NK cell depletion from IFN-γ KO mice lead to increased clearance of mycoplasma organisms from the lung. Further studies demonstrated that NK cells in an IFN-γ deficient environment lead to increased secretion of IL-10, G-CSF, and TNF-α and increased numbers of cell infiltrated into the alveoli and airways. These results suggest that NK cells of the lung have anti-inflammatory roles that IFN-γ counteracts in BALB/c mice. Regardless, these studies demonstrate that NK cells in an IFN-γ deficient environment impair innate immune responses from clearing mycoplasma organisms from the lung. These studies demonstrated diverse but novel functions for IFN-γ and IL-4 during respiratory infections that will have significant impact on future studies of respiratory immunology.