Arthritis research & therapy
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Arthritis Res. Ther. · Jan 2007
ReviewA critical appraisal of guidelines for the management of knee osteoarthritis using Appraisal of Guidelines Research and Evaluation criteria.
Clinical practice guidelines have been elaborated to summarize evidence related to the management of knee osteoarthritis and to facilitate uptake of evidence-based knowledge by clinicians. The objectives of the present review were summarizing the recommendations of existing guidelines on knee osteoarthritis, and assessing the quality of the guidelines using a standardized and validated instrument--the Appraisal of Guidelines Research and Evaluation (AGREE) tool. Internet medical literature databases from 2001 to 2006 were searched for guidelines, with six guidelines being identified. ⋯ Education and activity management interventions were superficially addressed in most guidelines. Guideline creators should use the AGREE criteria when developing guidelines. Innovative and effective methods of knowledge translation to health professionals are needed.
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Arthritis Res. Ther. · Jan 2007
Randomized Controlled Trial Multicenter Study Comparative StudyDevelopment of musculoskeletal toxicity without clear benefit after administration of PG-116800, a matrix metalloproteinase inhibitor, to patients with knee osteoarthritis: a randomized, 12-month, double-blind, placebo-controlled study.
We performed a randomized, double-blind, placebo-controlled, multicenter, parallel-group, dose-response study of the efficacy and safety of the oral administration of PG-116800, a matrix metalloproteinase (MMP) inhibitor, in patients with mild to moderate knee osteoarthritis. The primary efficacy endpoints included the progression of joint space narrowing in the osteoarthritic knee, as measured by microfocal radiography with fluoroscopic positioning, and the reduction of symptoms (pain and stiffness) and/or the improvement of function, as measured by the Western Ontario and McMaster Universities osteoarthritis index (WOMAC). Four hundred and one patients were randomly assigned to either placebo (n = 80) or one of fourdoses of PG-116800: 25 mg (n = 81), 50 mg (n = 80), 100 mg (n = 80), or 200 mg (n = 80) taken twice daily for 12 months. ⋯ The threemost frequent shoulder adverse events were reversible arthralgia, stiffness, and myalgia, which mostly affected the twohighest dose groups. The unfavorable risk-benefit balance of the MMP inhibitor PG-116800 in patients with knee osteoarthritis precludes further development of the compound for this indication. This study adds to the weight of evidence suggesting that side effect profiles of MMP inhibitors in general make them unsuitable for use in osteoarthritis.
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Arthritis Res. Ther. · Jan 2007
Comparative StudyCatechol-O-methyltransferase gene haplotypes in Mexican and Spanish patients with fibromyalgia.
Autonomic dysfunction is frequent in patients with fibromyalgia (FM). Heart rate variability analyses have demonstrated signs of ongoing sympathetic hyperactivity. Catecholamines are sympathetic neurotransmitters. ⋯ In our group of Spanish patients, there was an association between FM and the COMT haplotype previously associated with high pain sensitivity. This association was not observed in Mexican patients. Studies with a larger sample size are needed in order to verify or amend these preliminary results.
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Arthritis Res. Ther. · Jan 2007
Prostaglandin PGE2 at very low concentrations suppresses collagen cleavage in cultured human osteoarthritic articular cartilage: this involves a decrease in expression of proinflammatory genes, collagenases and COL10A1, a gene linked to chondrocyte hypertrophy.
Suppression of type II collagen (COL2A1) cleavage by transforming growth factor (TGF)-beta2 in cultured human osteoarthritic cartilage has been shown to be associated with decreased expression of collagenases, cytokines, genes associated with chondrocyte hypertrophy, and upregulation of prostaglandin (PG)E2 production. This results in a normalization of chondrocyte phenotypic expression. Here we tested the hypothesis that PGE2 is associated with the suppressive effects of TGF-beta2 in osteoarthritic (OA) cartilage and is itself capable of downregulating collagen cleavage and hypertrophy in human OA articular cartilage. ⋯ These studies show that PGE2 at concentrations much lower than those generated in inflammation is often chondroprotective in that it is frequently capable of selectively suppressing the excessive collagenase-mediated COL2A1 cleavage found in OA cartilage. The results also show that chondrocyte hypertrophy in OA articular cartilage is functionally linked to this increased cleavage and is often suppressed by these low concentrations of added PGE2. Together these initial observations reveal the importance of very low concentrations of PGE2 in maintaining a more normal chondrocyte phenotype.
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Arthritis Res. Ther. · Jan 2007
Increased serum levels of macrophage migration inhibitory factor in patients with primary Sjögren's syndrome.
The objective of this study was to analyse levels of the proinflammatory cytokine macrophage migration inhibitory factor (MIF) in patients with primary Sjögren's syndrome (pSS) and to examine associations of MIF with clinical, serological and immunological variables. MIF was determined by ELISA in the sera of 76 patients with pSS. Further relevant cytokines (IL-1, IL-6, IL-10, IFN-gamma and TNF-alpha) secreted by peripheral blood mononuclear cells (PBMC) were determined by ELISPOT assay. ⋯ Our data indicate that MIF might participate in the pathogenesis of primary Sjögren's syndrome. MIF may contribute to B-cell hyperactivity indicated by hypergammaglobulinemia. The inverse relationship of IL-10 and MIF suggests that IL-10 works as an antagonist of MIF in pSS.