Aim: To describe the longitudinal active joint count (AJC) trajectories in juvenile idiopathic arthritis (JIA). Methods: A retrospective cohort study at two Canadian centres was performed. The longitudinal trajectories of AJC were described using latent growth curve modeling. The association of baseline characteristics stratified by trajectory group was examined by univariate methods. Results: Data were analyzed for 659 children diagnosed with JIA between 1990/03-2009/09. A maximum of 10 years of follow-up data were included in the analysis. Participants were classified into 5 statistically and clinically distinct AJC trajectories by latent GCM. Conclusions: Using a novel longitudinal statistical method we were able to classify patients with JIA based on their pattern of AJC over time. The trajectory classes need to be examined for their relationship to important genetic and biological predictors. Identification of patterns of disease course is important in working towards the development of a clinically relevant outcome-based classification system in JIA.

Aim: To describe the longitudinal active joint count (AJC) trajectories in juvenile idiopathic arthritis (JIA). Methods: A retrospective cohort study at two Canadian centres was performed. The longitudinal trajectories of AJC were described using latent growth curve modeling. The association of baseline characteristics stratified by trajectory group was examined by univariate methods. Results: Data were analyzed for 659 children diagnosed with JIA between 1990/03-2009/09. A maximum of 10 years of follow-up data were included in the analysis. Participants were classified into 5 statistically and clinically distinct AJC trajectories by latent GCM. Conclusions: Using a novel longitudinal statistical method we were able to classify patients with JIA based on their pattern of AJC over time. The trajectory classes need to be examined for their relationship to important genetic and biological predictors. Identification of patterns of disease course is important in working towards the development of a clinically relevant outcome-based classification system in JIA.

Purpose: The primary purpose of this project was to determine the effect of aquatic exercise and aquatic exercise combined with an education group program on decreasing both psychosocial and physical fall risk factors in community-dwelling older adults with hip osteoarthritis (OA). Secondary purposes were to 1) describe fall risk, history and nature of falls and near-falls in older adults with hip OA, 2) determine the association of the timed up and go test (TUG) to history of falls and near-falls, 4) explore the relationship of both psychosocial and physical factors to history of falls and near-falls, and 5) evaluate the role of falls-efficacy in predicting balance performance. Methods: Participants were recruited from the community and screened for presence of hip osteoarthritis and fall risk. Baseline fall history and a battery of measures for balance, muscle strength, functional ability and falls-efficacy were administered. Participants were then randomly assigned to one of three groups: Aquatic Exercise, Aquatic Exercise and Education or a Control Group. The interventions were twice per week for 11 weeks. Fall risk factors were measured after 11 weeks. Study 1 described history of falls and near-falls and evaluated the association of the TUG screening test with fall and near-fall history. Study 2 summarized the relationships of physical and psychosocial fall risk factors and identified the primary predictors of fall risk, based on associations with fall history. Study 3 evaluated the randomized controlled clinical trial comparing the impact of the interventions (aquatic exercise and education) on fall risk outcomes. Results: Older adults with hip OA reported a high frequency of falls and near-falls. The TUG, using a cut-off score of 10 sec., was associated with frequent near-fall history. There was a strong association of frequent near-falls to history of actual falls, with the association increasing 7-fold if lower falls-efficacy was present. Falls-efficacy was also an independent predictor of balance impairment. Screening for history of near-falls and falls-efficacy may be important in predicting risk of future falls. The combination of Aquatic Exercise and Education improved falls-efficacy and functional mobility compared to Aquatic Exercise only or no intervention. Aquatic Exercise on its own was not effective in decreasing fall risk factors or improving falls-efficacy. Significance of Findings: The accumulation of both physical and psychosocial risk factors in older adults with hip OA increases their vulnerability to falls and injury. Fall prevention programs for this population should be designed to include both exercise and education to address falls-efficacy and physical fall risk factors.

<p>Knee pain is a common complaint among older Americans, nearly half of whom have developed or will develop painful osteoarthritis. Osteoarthritis is primarily a disease of articular cartilage, the low-friction, shock-absorbing connective tissue that lines long bones at their articulating surfaces. Within these joint tissues and within arthritis, the minor protein collagen VI plays an uncertain role, although it has been implicated in several muscle and ligament disorders. Determination of the collagen VI role in bone and cartilage of the knee is the focus of this dissertation.</p><p>Within articular cartilage, collagen VI exclusively localizes to and delimits the pericellular matrix (PCM), which differs from the extracellular matrix (ECM) in composition and structure. To interact with the cell, a molecule must first pass through the PCM. Fluorescent dextran diffusivities were quantified in the cartilage PCM using a newly developed model of scanning microphotolysis (SCAMP), a line photobleaching technique. Diffusion was slower in the PCM than in the ECM, although not in early-stage arthritic tissue. These results support the hypothesis that diffusivity is lower in the PCM than in the ECM of healthy articular cartilage, presumably due to differences in proteoglycan content. </p><p>Arthritic degradation is partly mediated by interleukin-1 (IL-1), a catabolic cytokine that affects the mechanical properties of articular cartilage and preferentially binds to cell-surface receptors in the surface zone. Since cells are the cartilage metabolic units, matrix degradation is hypothesized to influence molecular transport in the PCM before the ECM. Cartilage was cultured with or without IL-1, soaked in FITC-ovalbumin, and photobleached using SCAMP to measure diffusivity. Over 7 days of culture, IL-1 doubled the diffusivity in both zones (surface, middle) and matrices (PCM, ECM) of the cartilage. Diffusivity within the PCM was slightly lower than within the ECM. No increase in PCM diffusivity relative to ECM diffusivity was detected within either zone, suggesting that PCM-localized degradation either cannot be distinguished at these time points or cannot be detected by measures of ovalbumin diffusion.</p><p>To determine the effects of collagen VI absence on the morphometry and physical properties of the joint, knees of 2-, 9-, and 15-month-old Col6a1+/+ and Col6a1-/- mice were studied. Bone morphometry was evaluated using micro-computed tomography (microCT). Subchondral bone thickness, joint-capsule thickness, and cartilage degradation were assessed by histology. Cartilage elastic modulus, roughness, and coefficient of friction were measured by atomic force microscopy (AFM). Diffusion through the cartilage ECM was determined by SCAMP. Overall, collagen VI absence had profound effects on the morphometry of the proximal tibia and the overall histological structures of the mouse knee, yet minimal effects on the friction, roughness, elastic modulus, and diffusional properties of the articular cartilage. Musculoskeletal abnormalities at the knee do result from collagen VI absence.</p> / Dissertation

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder that may affect many tissues and organs but principally attacks synovial joints. All the symptoms of RA are mainly caused by cell inflammation, which results in cellular infiltration and synovial hyperplasia, finally leading to severe bone erosion. Existing drugs (steroids, non-steroid antiinflammatory drugs, disease-modifying anti-rheumatic drugs, etc.) can attenuate the symptoms of RA; however, these drugs also have many side effects. Therefore, it is necessary to discover new drugs for RA. Excavatolide B (Exc-B) is derived from the gorgonian coral. In our preliminary observations, Exc-B strongly inhibited lipopolysaccharide (LPS)-induced proinflammatory inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression in RAW264.7 macrophages. The present study also showed that Exc-B significantly attenuates the expressions of osteoclast-like gene, cathepsin K, and matrix metalloproteinase (MMP)-9 in LPS-treated RAW 264.7 cells. Moreover, in the adjuvant-induced RA animal model, Exc-B effectively reduced the swelling and arthritic index from the morphological viewpoint as well as reduced bone erosion and synovial hyperplasia from the pathological viewpoint. Our data indicates that Exc-B can inhibit disease progression in RA. Hence, Exc-B may serve as a useful therapeutic agent for the treatment of RA.

Rheumatoid arthritis (RA) is one kind of chronic inflammation disease. It affects not only joint, but often has the infringement outside the joint, such as internal organs. Besides the environmental factor, the heredity factor is involved in the pathogenesis of RA too. HLA-DR4 was found to play a role in RA pathogenesis in Taiwan. Because the DR4 positive patients actually are only one-half, other than HLA-DR gene may also be involved in RA pathogenesis. NF£eB plays an important role in immune inflammation. Activity of I£eB can affect NF£eB. I£eB£\ is a critical member in the I£eB protein family. Moreover, I£eBL is functionally similar to I£eB£\. Therefore we extrapolated polymorphisms of I£eBL gene and I£eB£\ gene of the RA patients and normal subjects. In this research, studies of these two genes from 79 RA patients and 81 normal subjects were divides into two parts. The first part used polymerase chain reaction, direct sequencing, special sequence polymerase chain reaction as well as limit fragment length polymorphism to study relations between I£eBL gene and HLA-DR4 and RA occurrence. The second part used polymerase chain reaction and limit fragment length polymorphism, to analyze relation between I£eB£\ gene and the RA occurrence. We found that there is significant increase of -421 -/A base deletion polymorphism in I£eBL gene from DR4 positive RA patients and -262 T/C polymorphism in I£eBL gene from DR4 negative RA patients. A significant reduction of -519 C/T polymorphism in I£eB£\ gene from DR4 negative RA patients was found too. In conclusion, polymorphisms of -421 -/A base deletion as well as -262 T/C in I£eBL gene may be involved in the pathogenesis of RA by alteration of I£eBL activity and thereafter binding of I£eBL to NF£eB.

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Thesis (Ph. D.)--University of Missouri-Columbia, 2001. / Typescript. Vita. Includes bibliographical references (leaves 83-86). Also available on the Internet.

Thesis (Ph. D.)--University of Missouri-Columbia, 2001. / Typescript. Vita. Includes bibliographical references (leaves 83-86). Also available on the Internet.

Thesis (doctoral)--Medizinische Hochschule, Hannover, 2000.