ARTHRITIS

Grant Number: 5P60AR20621-19
PI Name: ROTHFIELD, NAOMI F.
PI Title:
Project Title: ARTHRITIS

Abstract:
Five years of funding (Years 15-19) are requested for the renewal of the MAC with Dr. Rothfield as Director and Dr. Abeles as Associate Director. The Research Component will continue under the direction of Dr. Korn. Five D/Fs are proposed: D/F1-A Transgenic Approach to the Mechanism of Tissue Destruction in Arthritis - M. Hibbs, M.D.; D/F2 - The Role of Gamma/Delta T Cells in Collagen Induced Arthritis - L. Lefrancois, Ph.D.; D/F3 - Effects of Anti-Inflammatory Drugs on Lymphocyte Adhesion - T. Piela-Smith, Ph.D.; D/F4 - Effect of Implant Materials on Human Osteoblast Cultures - G. Gronowicz, Ph.D.; D/F5 - Evaluation of the Tight Skin Mutation in Chimeric Mice - S. Clark, Ph.D. The Education, Epidemiology, Health Services Research Component will continue under the direction of Susan Reisine, Ph.D. Activities will be coordinated by Frances Ingenito, N.P. and carried out by the MAC faculty and the Teaching Team. Dr. Parke will continue as the Physician Education Coordinator with Robert Rippey, Ph.D. as consultant. Two Research Projects and one D/F are proposed: Project 1 - Daily Processes in Primary Fibromyalgia - Glenn Affleck, Ph.D.; Project 2 - A National Study of Role Limitations in Rheumatoid Arthritis Patients - Susan Reisine, Ph.D.; D/F1 - A Work Stress Instrument: Development and Evaluation - is requested for data acquisition and analysis for the component projects and D/F and to make our existing data sets available to others. Renewal of the Statistics and Database Core under the direction of Jonathan Clive, Ph.D. is requested to provide statistics, database and epidemiology support and expertise for ongoing and proposed research. An Administrative Unit will continue the overall administration of the Center.

Thesaurus Terms:
connective tissue disorder

Institution: UNIVERSITY OF CONNECTICUT SCH OF MEDICINE AND DENTISTRY
FARMINGTON, CT 06032
Fiscal Year: 1997
Department: MEDICINE
Project Start: 30-SEP-78
Project End: 31-DEC-98
ICD: NAT INST OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
IRG: AMS

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GONADAL STEROID HORMONAL REGULATION OF PESISTENT PAIN

Grant Number: 1R01DE12757-01
PI Name: REN, KE
PI Title:
Project Title: GONADAL STEROID HORMONAL REGULATION OF PESISTENT PAIN

Abstract:
Chronic or persistent pain affects millions of adults each year with costs in lost work days, medical treatment and the reduction in the quality of life in the range of billions of dollars. Many of these conditions are gender-related. Women exhibit a higher prevalence of temporomandibular disorders, neuropathic pain, fibromyalgia, migraine headaches and some forms of arthritis. Furthermore, variations in hormonal levels associated with menstrual cycle, menopause, pregnancy and lactation influence pain levels.

The purpose of this study is to evaluate the effects of progesterone and progesterone in combination with estrogen on the hyperalgesia and neuronal hyperexcitability associated with a rat model of persistent pain and inflammation. Our major hypothesis is that endogenous reproductive hormones can suppress persistent pain by their influence on a cascade of molecular, biochemical and physiological events at the spinal level involving inhibitory and excitatory amino acids and their receptors, and opioid peptides and their receptors. We will investigate the effects of these hormones on behavioral hyperalgesia, spinal cord neurons, modulation of GABA receptors, expression of opioid receptors and opioid peptides, and NMDA receptor function.

Specific Aim 1 will characterize the changes in behavioral inflammatory hyperalgesia produced by progesterone, in lactating females, ovariectomized females with hormone replacement, and castrated males.

Specific Aim 2 will determine the effects of progesterone on the development and maintenance of behavioral hyperalgesia, as well as the possible target sites of the antihyperalgesic effects in peripheral tissue, the spinal cord and the brain.

Specific Aim 3 will determine that progesterone's antihyperalgesic effects are mediated, in part, via modulation of GABAA receptor activation.

Specific Aim 4 will test the hypothesis that progesterone's antihyperalgesic effects are opioid-mediated, in part, at the level of the spinal cord.

Specific Aim 5 will examine progesterone effects on NMDA receptor function and changes in NMDA receptor subunit gene expression following inflammation and hyperalgesia. In summary, we propose to elucidate the influence of reproductive hormones on mechanisms of persistent pain in a rat model that mimics human chronic pain conditions known to exhibit cyclical or pregnancy-related variations. The findings will be important for the development of new approaches to the management of these conditions.

Thesaurus Terms:
analgesia, chronic pain, estrogen, hormone regulation /control mechanism, hyperalgesia, progesterone, GABA receptor, NMDA receptor, castration, inflammation, lactation, opioid, opioid receptor, receptor expression, spinal cord, laboratory rat

Institution: UNIVERSITY OF MARYLAND BALT PROFESSIONAL SCHOOLS
BALTIMORE, MD 21201
Fiscal Year: 1999
Department: ORAL SURGERY
Project Start: 01-SEP-99
Project End: 31-AUG-03
ICD: NATIONAL INSTITUTE OF DENTAL RESEARCH
IRG: ZDE1

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MULTIPURPOSE ARTHRITIS & MUSCULOSKELETAL DISEASES CENTER
Grant Number: 5P60AR20614-22
PI Name: KIMBERLY, ROBERT
PI Title:
Project Title: MULTIPURPOSE ARTHRITIS & MUSCULOSKELETAL DISEASES CENTER

Abstract:
The Multipurpose Arthritis and Musculoskeletal Diseases Center (MAMDC) of the University of Alabama at Birmingham (UAB) is a multidisciplinary effort, involving faculty and staff of the Schools of Medicine, Dentistry, Nursing, Public Health, and Health Related Professions, and the University Hospital. A broad spectrum of biomedical, epidemiologic, education, and health services-based research efforts is focused on substantive problems posed by the rheumatic and musculoskeletal diseases. Biomedical research in the UAB MAMDC includes studies in the areas of immunology, virology, molecular biology, immunogenetics, connective tissue biochemistry, and clinical rheumatology. This application includes five new biomedical research feasibility proposals addressing basic processes relevant to the pathogenesis of the rheumatic and musculoskeletal diseases. Three Research Core Units are also proposed: continuation of the highly successful Hybridoma and Flow Cytometry Core Facilities and initiation of the MAMDC Gene Targeting Core Facility. Three projects are proposed which address fundamental epidemiology, education and health services problems related to the rheumatic diseases. Proposed efforts include projects directed toward: 1) investigating the impact of telephone counseling on outcomes and economic impact of disease in patients with SLE; 2) investigating approaches to improving outcomes of vocational rehabilitation in patients with musculoskeletal diseases; and 3) elucidating mechanisms underlying pain in fibromyalgia. The overall goals of the MAMDC are to coordinate existing arthritis and musculoskeletal disease research programs and initiate new ones so that we can achieve: (1) greater knowledge of the etiologies and pathogenetic mechanisms underlying rheumatic and musculoskeletal diseases; (2) improved therapies for these diseases; (3) better methods of health education; (4) elucidation of epidemiologic aspects of arthritis and related conditions; (5) improvement of patient services; and (6) a more enlightened community attitude towards arthritis and the musculoskeletal diseases.

Thesaurus Terms:
arthritis, functional ability, musculoskeletal disorder, outcomes research, pathologic process, behavioral /social science research tag

Institution: UNIVERSITY OF ALABAMA AT BIRMINGHAM
UAB STATION
BIRMINGHAM, AL 35294
Fiscal Year: 1999
Department: MEDICINE
Project Start: 20-SEP-77
Project End: 31-DEC-01
ICD: NAT INST OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
IRG: AMS

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PLANNING GRANT FOR MULTIPURPOSE CRCS
Grant Number: 1P20AR46667-01
PI Name: GALBRAITH, RICHARD A.
PI Title:
Project Title: PLANNING GRANT FOR MULTIPURPOSE CRCS

Abstract:
The goal of this P20 Planning Grant Application from the University of Vermont is to build the infrastructure to support the intellectual interactions that will lead to a collaborative multidisciplinary clinical research program focusing on musculoskeletal function and dysfunction. The overall goal is to compete for a P60 Multipurpose Clinical Research Center Award. The University of Vermont and its affiliated teaching hospital, Fletcher Allen Health Care, has a wide range of successful, funded investigators working in basic, translational and clinical research fields with an emphasis on musculoskeletal disease. In addition, being the only tertiary health care facility in the State of Vermont, there are adequate numbers of patients with diseases which fall within the purvue of NIAMS and there is a past history of willingness of patients to enroll in and complete clinical research trials at the General Clinical Research Center and elsewhere in the outpatient system. The application details this research base and the supporting resources and existing Centers which will augment and foster the kinds of clinical research projects which will be included in the P60 application. The application also details the infrastructure which will be established to achieve these goals and our plans for the use of Internal and External Advisory Committees and the prominent role of the Biostatistics/Research Core. Finally, the application also includes examples of the kinds of interactions and synergies which have already arisen from the discussions of interested investigators. Examples include, but are not limited to, magnetic resonance imaging and outcomes studies to assess factors which lead to osteoarthritis of the knee following partial meniscectomy; the synergistic addition of studies of neuromuscular control to biomechanical studies in acute back injuries and ankle sprains; the application of basic science studies to determine maximal shortening velocity of muscle fibers, myosin and actin force and interaction, and mitochondrial function and DNA mutations in patients who have fibromyalgia syndrome; the use of an experimental dense multichannel EMG array in conjunction with real-time ultrasound imaging to gain a better understanding of the etiology of idiopathic low back pain; and studies of the interactions between eccentric exercise, muscle damage and postural stability with a view to reducing falls in the elderly and studying chronic musculoskeletal conditions such as rheumatoid arthritis and disuse atrophy. These or other examples could be further refined and expanded if this application were successful and where appropriate, the resources of the existing NIH-funded General clinical Research Center could be leveraged to perform resulting clinical research and outcomes projects.

Thesaurus Terms:
health science research potential, interdisciplinary collaboration, musculoskeletal disorder

Institution: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
BURLINGTON, VT 05405
Fiscal Year: 1999
Department: NONE
Project Start: 30-SEP-99
Project End: 29-SEP-00
ICD: NAT INST OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
IRG: ZAR1

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ARTHRITIS AND MUSCULOSKELETAL DISEASES CENTER
Grant Number: 2P60AR20557-20
PI Name: FOX, DAVID A.
PI Title:
Project Title: ARTHRITIS AND MUSCULOSKELETAL DISEASES CENTER

Abstract:
The University of Michigan Multipurpose Arthritis and Musculoskeletal Diseases Center (UM-MAC) will provide the leadership and environment necessary to coordinate the multiple resources of the University of Michigan in support of arthritis-related research, education and patient care. This will be accomplished by a broad-based, inclusive approach that crosses traditional clinical and scientific boundaries. The Center involves over 100 faculty members from multiple departments and schools of The University of Michigan who have made substantial commitments to the support of arthritis-related programs. The leadership of the Center will foster collaboration between individual investigators and programs, closely monitor progress in UM-MAC funded research projects and cores, organize comprehensive educational programs, and ensure that the UM-MAC is responsive to the needs of the community. The UM-MAC is divided into two major components: 1) the Biomedical Research Division; 2) the Education, Epidemiology and Health Services Research Division; both supported by the administrative unit. Within the Biomedical Research Division the six major scientific programs are: 1) Genetic Mechanisms, 2) Immunobiology, 3) Mechanisms of Tissue Destruction, Repair and Aging, 4) Development and Application of Imaging Techniques, 5) Orthopedics and Biomechanics, and 6) Organogenesis. In support of these major programs, funding is requested for none core facilities: 1) Flow Cytometry Core, 2) Hybridoma Core, 3) Molecular Biology Core, 4) Protein Structure and Design Core , 5) Biomechanics and Image Processing Core, 6) Biostatistics Core, 7) Transgenic Animal Core, 8) Vector Core and 9) DNA Sequencing Core. Three Developmental and feasibility projects are proposed for funding in years one through three, representing novel approaches to questions in the areas of immunology and musculoskeletal organogenesis. Additional funds are requested for developmental and feasibility projects to be competitively awarded during years three and four. Within the Education, Epidemiology and Health Service Research Division, there are four major programs, 1) Education, 2) Epidemiology, 3) Clinical Investigation and 4) Health Services Research, Funding is requested for three research projects: 1) Biomarker of osteoarthritis: The epidemiology, 2) Evaluating and reinforcing arthritis patient education for urban African Americans, and Cognitive and neurochemical function in fibromyalgia. The UM-MAC will also form interdisciplinary working groups focused on specific diseases, in order to better link BRD and E/E/HSR investigators to facilitate innovative research directed at issues directly related to specific arthritic and musculoskeletal diseases. This proposal incorporates many new investigators from a variety of departments, and reflects success of the UM-MAC in its current funding cycle in attracting diverse new talent into research related to rheumatic diseases at The University of Michigan.

Thesaurus Terms:
arthritis education

Institution: UNIVERSITY OF MICHIGAN AT ANN ARBOR
ANN ARBOR, MI 48109
Fiscal Year: 1998
Department: INTERNAL MEDICINE
Project Start: 20-SEP-77
Project End: 31-DEC-01
ICD: NAT INST OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
IRG: ZAR1

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MECHANISMS OF MIND-BODY INTERACTION: EMOTION INTERFACE
Grant Number: 3P50MH61083-01S1
PI Name: DAVIDSON, RICHARD J.
PI Title:
Project Title: MECHANISMS OF MIND-BODY INTERACTION: EMOTION INTERFACE

Abstract:
This Center will focus on mechanisms of mind-body interaction with an emphasis on emotion as a core intermediary level through which psychosocial influences and interventions exert their effects and thereby influence health. The Center builds upon the strength in research on emotion at Wisconsin. We conceptualize emotion as the key mediating variable through which social influences get transduced and impact upon the organism to influence autonomic, endocrine and immune function and thus effect health. Emotion is instantiated in elements of brain circuitry that have now been characterized. We highlight three regions-the prefrontal cortex, amygdala, and hippocampus-that play an important role in subserving emotion and in influencing other biological systems that have health-relevance. Project 1 will focus on later life resilience and vulnerability and will study psychosocial and biological processes in older women who have been followed through the major life transition of relocation. Project 2 will focus on well-being, symptom expression, endocrine and immune function in women with two musculoskeletal conditions, fibromyalgia (FMS) and rheumatoid arthritis (RA). In addition, this study will evaluate the impact of mindfulness meditation on emotion, symptom expression and immune and endocrine function in these patients. Project 3 will use samples from Projects 1 and 2 to study the functional neural circuitry of emotion (with fMRI), structural integrity of the hippocampus and peripheral psychophysiology of resilient and vulnerable individuals. In a second study, this project will also collect these measures in patients from Project 2 before and after they participate in the mindfulness meditation intervention, Project 4 will study the biology and behavior of free-ranging rhesus monkeys to predict their reactivity to the naturally occurring stress of leaving their natal group. Project 5 will evaluate the efficacy of a group exercise program in older women with breast cancer and will assess emotion-related constructs as well as endocrine and immune function to examine the mechanisms by which this intervention may have salubrious effects. Project 6 will investigate linkages among life course social inequities, emotion-related variables and adult physical health in the context of several large epidemiological surveys and longitudinal studies. These projects will be supported by Administrative; Statistics; Mind-self-report and interviews; and Body-biological measures, cores. We are ideally positioned to significantly advance our scientific understanding of the mechanisms of mind-body interaction.

Thesaurus Terms:
emotional adjustment, psychological stressor, psychoneuroimmunology, psychophysiology, behavioral /social science research tag

Institution: UNIVERSITY OF WISCONSIN MADISON
500 LINCOLN DR
MADISON, WI 53706
Fiscal Year: 1999
Department: PSYCHOLOGY
Project Start: 24-SEP-99
Project End: 31-AUG-04
ICD: NATIONAL INSTITUTE OF MENTAL HEALTH
IRG: ZRG1

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SOCIAL SUPPORT/HEALTH CARE USE IN FIBROMYALGIA

Grant Number: 5R01AR044020-04
PI Name: CRONAN, THEREASA A.
PI Title: DIRECTOR
Project Title: SOCIAL SUPPORT/HEALTH CARE USE IN FIBROMYALGIA

Abstract: THIS IS A SHANNON AWARD PROVIDING PARTIAL SUPPORT FOR THE RESEARCH PROJECTS THAT FALL SHORT OF THE ASSIGNED INSTITUTE'S FUNDING RANGE BUT ARE IN THE MARGIN OF EXCELLENCE. THE SHANNON AWARD IS INTENDED TO PROVIDE SUPPORT TO TEST THE FEASIBILITY OF THE APPROACH; DEVELOP FURTHER TESTS AND REFINE RESEARCH TECHNIQUES; PERFORM SECONDARY ANALYSIS OR AVAILABLE DATA SETS; OR CONDUCT DISCRETE PROJECTS THAT CAN DEMONSTRATE THE PI'S RESEARCH CAPABILITIES OR LEND ADDITIONAL WEIGHT TO AN ALREADY MERITORIOUS APPLICATION. THE ABSTRACT BELOW IS TAKEN FROM THE ORIGINAL DOCUMENT SUBMITTED BY THE PRINCIPAL INVESTIGATOR. DESCRIPTION: The long-term objective of the proposed study is to save money on health care by applying behavioral methods. A previous study showed that social support, education, and a combination of the two reduced use of the health care system, thus saving money, and improved health status. The study now proposed would build on the previous study by extending two of the three earlier interventions from the osteoarthritis patients studied earlier to fibromyalgia patients. The latter tend to be younger and to experience more widespread pain. If the generalization is successful, cost-saving techniques can be disseminated. The proposed study will be conducted in two phases. During Phase I, hematologists and family practitioners will identify situations in which contacts with the health care system are unnecessary. During Phase II, 312 health maintenance organization members with fibromyalgia will be randomly assigned to a social support, a combined education and social support condition, or a control group. Both experimental groups will have 2-hour weekly meetings for 10 weeks, and then 2-hour monthly meetings for 10 months. Participants assigned to the social support condition will spend their time developing an enduring support group. People assigned to receive a combination of social support and education will also receive the information, developed during Phase I, about when to use the health care system. The third group will serve as a no- treatment control. In addition, a group of 104 non- volunteers will be compared to the control group of volunteers. Five "waves" of 63 patients will be studied. Utilization will be determined via medical records and health status via the Quality of Well-being Scale. Participants will be followed for 18 months. Several mediating variables will be studied to determine their effects on the major outcome variables, and cost-benefit and cost-utility models will be developed. If either of the interventions reduce health care costs by $1200 per person per year, as expected, the long- term savings will be great.

Thesaurus Terms: fibromyalgia, health behavior, health care service evaluation, health care service utilization, health education, social support network behavior therapy, managed care, quality of life behavioral /social science research tag, clinical research, health services research tag, human middle age (35-64), human subject, outcomes research, questionnaire

Institution: SAN DIEGO STATE UNIVERSITY
Fiscal Year: 2000
Department: PSYCHOLOGY
Project Start: 30-SEP-1996
Project End: 28-FEB-2002
ICD: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
IRG: BEM

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CENTER FOR ALTERNATIVE MEDICINE RESEARCH OF ARTHRITIS
Grant Number: 1P50AT00084-01
PI Name: BERMAN, BRIAN M.
PI Title:
Project Title: CENTER FOR ALTERNATIVE MEDICINE RESEARCH OF ARTHRITIS

Abstract:
Arthritis and related musculoskeletal disorders are a leading cause of disability, and usage of complementary and alternative medicine (CAM) interventions i particularly high among those with the severest forms of these conditions. Although largely unproven, these therapies are commonly sought by those experiencing the severest disease and frequently used in combination with other alternative or conventional treatments. There is, thus, a great unmet need to evaluate the safety, efficacy, and cost-effectiveness of these CAM interventions in a collaborative setting in which experts in rheumatology, complementary medicine, epidemiology, statistics and health services research approach these questions in a scientifically rigorous, multi-disciplinary manner. The major objective of this application is the establishment of a specialized center for research in complementary and alternative medicine (CAM) focusing on arthritis and related diseases at the University of Maryland Baltimore. The Center for Alternative Medicine Evaluation and Research in Arthritis (CAMERA) will support a multi-disciplinary team of researchers and develop institutional and regional collaborations to conduct clinical and basic research exploring the potential efficacy, safety, and cost-effectiveness of long-term outcomes following acupuncture treatment for osteoarthritis of the knee; 2) the effectiveness of mind/body therapies for fibromyalgia; 3) the mechanism of action and effects of electroacupuncture on persistent pain & inflammation; and 4) the mechanism of action of a herbal combination with immunomodulatory properties. The Center will create core resource facilities to support, monitor and evaluate its research activities. Future investigation of CAM and arthritis and related disorders will be encouraged through: 1) the training of new investigators in the Center's Career Development & Training Program, and 2) the Development and Feasibility Research Program, which will solicit, meritoriously evaluate and support innovative pilot research.

Thesaurus Terms:
alternative medicine, arthritis, arthritis therapy, human therapy evaluation, nonhuman therapy evaluation

Institution: UNIVERSITY OF MARYLAND BALT PROFESSIONAL SCHOOLS
BALTIMORE, MD 21201
Fiscal Year: 1999
Department: MEDICINE
Project Start: 30-SEP-99
Project End: 31-JUL-04
ICD: AGENCY FOR TOXIC SUBSTANCES AND DISEASE REGISTRY
IRG: ZRG1

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