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ID PMID Title PublicationDate abstract
18551351 Proposals for leflunomide use to avoid lung injury in patients with rheumatoid arthritis. 2008 Among the 5,043 consecutive patients registered in the postmarketing surveillance for leflunomide, 61 were reported to have lung injury and 24 died from it. The adjusted multivariate logistic regression analysis of the risk factors showed that preexisting interstitial lung disease posed the greatest risk, as well as loading dose, smoking history, and low body weight of 40 kg or less with odds ratios of 8.17, 3.97, 3.12, and 2.91, respectively. In 12 patients, lung injury developed even 2 months after leflunomide withdrawal. When patients with (n=9) and without (n=13) fatal outcome were compared, eight out of the former, and six out of the latter had preexisting interstitial lung disease; the former showed severe hypoxemia, high serum C-reactive protein level, hypoalbuminemia, and continuous lymphocytopenia, and required mechanical ventilation. On the basis of these results and literature review, the committee proposes that leflunomide should only be recommended as a second-line drug, should not be administered to patients with preexisting interstitial lung disease, should also not be administered to patients with smoking history or those with low body weight, and should be administered without loading dose. Careful monitoring is necessary, and when lung injury develops, leflunomide elimination using colestyramine is mandatory.
17143598 Correlation between Yersinia enterocolitica and type I collagen reactivity in patients wit 2007 May We investigated the association with Yersinia infection in patients with arthropathies in our region. To assess the reactivity to articular antigens, the correlation of anti-Yersinia with anti-type I and type II collagen antibodies was studied. Sera from 124 patients with musculoskeletal symptoms, and 47 synovial fluids (SF) from patients with rheumatoid arthritis (RA), spondyloarthopathies (SpA) or osteoarthritis (OA) were examined. Immunoglobulins against Yersinia enterocolitica, type I and type II collagens were determined by enzyme-linked immunosorbent assay. Immunoglobulin (Ig) A to Yersinia lipopolysaccharide (LPS) was present in 13/124 sera (10%) and 3/47 SF (6%). By Western blot, IgA to Yersinia outer proteins (Yops) was found in 14/124 sera (11%) and 2/47 SF (4%). Yersinia DNA from SF was not amplified by polymerase chain reaction. We found a significant correlation with anti-collagen type I but not type II antibodies. These results suggest different reactivity to articular collagen in patients with Yersinia antibodies.
18250113 Cellular distribution of the C-type II lectin dendritic cell immunoreceptor (DCIR) and its 2008 Dec OBJECTIVE: An association to variations in the dendritic cell immunoreceptor (DCIR) gene with rheumatoid arthritis (RA) was recently shown. However, protein expression of DCIR has so far not been assessed in a disease setting. In the present work, we aimed to determine the cellular and tissue distribution of this receptor in healthy controls and in patients with RA before and after local glucocorticoid administration. METHODS: DCIR mRNA expression was evaluated by quantitative PCR (n=3) and protein expression by flow cytometry (n=18), immunohistochemistry (n=14) and double immunofluorescence (n=5). RESULTS: DCIR protein was not detected in healthy synovia. By contrast, expression was abundant on cells from rheumatic joints in synovial fluid and in tissue. Following corticosteroid treatment this expression was downregulated. Interestingly, DCIR could be detected on natural killer (NK) cells and T cells, and CD4+ and CD8+, as well as on monocytes, B cells, dendritic cells and granulocytes. The frequency of DCIR+ T cells and the level of surface expression were increased in the rheumatic joint compared to blood. In synovial fluid the typical DCIR+ T cells were large activated cells, whereas blasted DCIR+ T cells were not detected in blood. CONCLUSIONS: We demonstrate increased protein and mRNA expression of DCIR in RA, especially in the rheumatic joint. Expression was widespread and included a subpopulation of T cells. This suggests that the inflammatory synovial environment induces DCIR expression, and this may be related to synovial T cell function. Ligation of DCIR, or lack thereof, could contribute to the chronic inflammation characterising autoimmune diseases such as RA.
17983151 Collagen antibody induced arthritis. 2007 Rheumatoid arthritis (RA) is a polygenic and multifactorial disease. Many complex immunological and genetic interactions are involved in the final out come of the clinical disease. To understand the various disease pathways operating during the disease course, we need many different animal models. Collagen induced arthritis (CIA) is one of the widely used animal models sharing many pathological and histological similarities with RA and antibodies play an important role in the inflammatory phase of CIA. This chapter describes, in detail, an animal model for arthritis using CII specific monoclonal antibodies, the so-called collagen antibody induced arthritis (CAIA), which shares many characteristics of CIA. CAIA model provides an opportunity to study the inflammatory phase of arthritis without involving the priming phase of the immune response. CAIA can be used for not only studying inflammatory processes in arthritis and screening drug candidates controlling joint inflammatory phase but also as a model for studying common mechanisms involved in many antibody mediated diseases.
18807388 [Cost study of NSAID use in rheumatoid arthritis based on recent therapeutic protocols]. 2008 In today's health care beside the medical perspective, economic aspects should also be taken into consideration. Because of the significant opportunity-cost, only the most cost-effective techniques should be subsidized, which result the highest net-benefit for the society. This paper focuses on the economic aspects of the chronic NSAID use in rheumatoid arthritis. Based on recent therapeutic protocols a cost study (partial economic evaluation) was carried out. Our results indicate that for patients with an average GI-risk retard diclofenac could be a possible good choice. For patients with moderate to severe GI risk, retard diclofenac + pantoprazole combination therapy should be prescribed. COX-2 inhibitors are advised only for a limited group of patients with specific conditions; because of their higher price and side effect profile (severe CV adverse effect and uncertain GI benefits). We would also highlight the importance of individual therapy. In complex our purpose was to evaluate current therapeutic guidelines from a pharmacoeconomic perspective.
17278921 Health literacy and arthritis research and practice. 2007 Mar PURPOSE OF REVIEW: The following review summarizes contributions from rheumatology to the growing field of health literacy. RECENT FINDINGS: Arthritis related publications have primarily contributed to one strand of research in health literacy: assessments of print materials and considerations of the match between the reading grade level of materials and the reading skills of intended audiences. Unlike researchers addressing other chronic diseases such as diabetes, however, researchers and practitioners in rheumatology have yet to examine links between patients' literacy skills and health outcomes. In addition, only one early study reports on evaluation findings of an education program designed for audiences with low literacy skills. No other studies report on efforts to increase health literacy in arthritis, reduce the demands of print materials for education or research purposes, or on efforts to ameliorate the effects of limited literacy skills among patients. SUMMARY: Health literacy may well influence arthritis outcomes as well as recruitment efforts in arthritis research. The 2004 report on health literacy from the Institute of Medicine calls for additional studies focused on the links between health literacy and health outcomes.
17009259 Matrix metalloproteinase 10 promotion of collagenolysis via procollagenase activation: imp 2006 Oct OBJECTIVE: We have previously reported the up-regulation of matrix metalloproteinase 10 (MMP-10) following treatment with the procatabolic stimulus of interleukin-1 (IL-1) and oncostatin M (OSM) in chondrocytes. Although MMP-10 is closely related to MMP-3, little is known about the role of MMP-10 in cartilage catabolism. The purpose of this study was to determine whether MMP-10 is expressed in connective tissue cells and to assess how it may contribute to cartilage collagenolysis. METHODS: MMP gene expression was assessed by real-time polymerase chain reaction using RNA from human articular chondrocytes and synovial fibroblasts stimulated with IL-1 plus OSM or tumor necrosis factor alpha (TNFalpha) plus OSM. Synovial fluid levels of MMP-10 were determined by specific immunoassay. Recombinant procollagenases were used in activation studies. Immunohistochemistry assessed MMP-10 expression in diseased joint tissues. RESULTS: MMP-10 expression was confirmed in both chondrocytes and synovial fibroblasts following stimulation with either IL-1 plus OSM or TNFalpha plus OSM, and MMP-10 was detected in synovial fluid samples from patients with various arthropathies. Exogenous MMP-10 significantly enhanced collagenolysis from IL-1 plus OSM-stimulated cartilage, and MMP-10 activated proMMP-1, proMMP-8, and proMMP-13. Immunohistochemistry revealed the presence of MMP-10 in the synovium and cartilage of an IL-1 plus OSM-induced model of arthritis as well as in samples of diseased human tissues. CONCLUSION: We confirm that both synovial fibroblasts and articular chondrocytes express MMP-10 following treatment with procatabolic stimuli. Furthermore, the detectable levels of synovial fluid MMP-10 and the histologic detection of this proteinase in diseased joint tissues strongly implicate MMP-10 in the cartilage degradome during arthritis. The ability of MMP-10 to superactivate procollagenases that are relevant to cartilage degradation suggests that this activation represents an important mechanism by which this MMP contributes to tissue destruction in arthritis.
17657679 Regional cerebral blood flow between primary and concomitant fibromyalgia patients: a poss 2007 May OBJECTIVES: Technetium-99m ethyl cysteinate dimer (Tc-99m ECD) brain single photon emission computed tomography (SPECT) has been used to detect abnormal regional cerebral blood flow (rCBF) in women with primary fibromyalgia (FM). The main aim of this study was to investigate the rCBF deficit in concomitant FM patients and compare it with primary FM. METHODS: An observational study was designed to analyse the SPECT findings in 92 female patients recruited from January 2002 to January 2004. Differences in the rCBF hypoperfusive areas between 49 primary and 29 concomitant FM patients were assessed in different areas of the brain using the chi(2)-test for statistical significance. RESULTS: Tc-99m ECD brain SPECT in 71 FM patients revealed heterogeneous rCBF in comparison to the homogeneous scan in 14 control patients. The most prominent rCBF hypoperfusive region in both primary and concomitant FM groups was the left temporoparietal area, followed by the thalamus, right temporoparietal, frontal, and basal ganglia areas. Differences in rCBF hypoperfusion in these areas for both FM groups were not significant (all p>0.5). CONCLUSIONS: Reduced rCBF at cortical regions, in addition to previously reported areas at the thalamus and the subcortical nucleus, in FM patients was demonstrated in this study. The perfusion deficit areas were similar between primary and concomitant FM when the underlying disease activity was quiescent. The feasibility of using this neuroimaging study to differentiate FM from the primary disease, such as rheumatoid arthritis (RA)-associated depression and neuropsychiatric lupus, should be considered.
16937498 Effects of chronic therapy with non-steroidal antiinflammatory drugs on gastric permeabili 2006 Aug 21 AIM: To evaluate the gastric permeability after both acute and chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) and to assess the clinical usefulness of sucrose test in detecting and following NSAIDs- induced gastric damage mainly in asymptomatic patients and the efficacy of a single pantoprazole dose in chronic users. METHODS: Seventy-one consecutive patients on chronic therapy with NSAIDs were enrolled in the study and divided into groups A and B (group A receiving 40 mg pantoprazole daily, group B only receiving NSAIDs). Sucrose test was performed at baseline and after 2, 4 and 12 wk, respectively. The symptoms in the upper gastrointestinal tract were recorded. RESULTS: The patients treated with pantoprazole had sucrose excretion under the limit during the entire follow-up period. The patients without gastroprotection had sucrose excretion above the limit after 2 wk, with an increasing trend in the following weeks (P = 0.000). A number of patients in this group revealed a significantly altered gastric permeability although they were asymptomatic during the follow-up period. CONCLUSION: Sucrose test can be proposed as a valid tool for the clinical evaluation of NSAIDs- induced gastric damage in both acute and chronic therapy. This technique helps to identify patients with clinically silent gastric damages. Pantoprazole (40 mg daily) is effective and well tolerated in chronic NSAID users.
16150791 New onset or exacerbation of psoriatic skin lesions in patients with definite rheumatoid a 2006 Mar BACKGROUND: Blockage of tumour necrosis factor alpha (TNFalpha) is highly effective in rheumatic diseases, especially in rheumatoid arthritis (RA), ankylosing spondylitis, and psoriatic arthritis. Furthermore, TNFalpha antagonists have also been shown to significantly reduce psoriatic skin lesions. CASE REPORTS: A series of nine patients with RA who were treated with different types of TNFalpha antagonists and who unexpectedly developed either a new onset or an exacerbation of psoriatic skin lesions are reported.
17828350 Imaging of psoriatic arthritis. 2007 Imaging of psoriatic arthritis (PsA) is important for two reasons: the differential diagnosis from other arthritides and the assessment of structural damage that can be inhibited by the new drugs such as the anti-TNFalpha agents. Plain film radiographic findings of peripheral arthritis have been important in elaborating the concept of PsA as a separate disease entity. Characteristic aspects of psoriatic peripheral arthritis help the differentiation from rheumatoid arthritis. High-resolution ultrasonography (US), US combined with power Doppler (PDUS) and magnetic resonance imaging (MRI) can be used to image joint synovitis of PsA. Radiologic features of spondylitis associated with psoriasis are similar to spondylitis associated with reactive arthritis and differ from those of primary ankylosing spondylitis (AS) and the spondylitis associated with inflammatory bowel disease. MRI is very sensitive for the early diagnosis of sacroiliitis. There have been no MRI studies on the spine of patients with PsA. In primary AS bone oedema in the vertebral bodies is an indicator of active disease and can ameliorate during anti-TNFalpha therapy. Historically, plain film radiography have played a pivotal role in defining enthesitis lesions of SpA. However, entheseal bone changes appear late. US and MRI have proved to be a highly sensitive and non invasive tools. Recent US and MRI studies on both finger and toe dactylitis have established that dactylitis is due to flexor tenosynovitis and marked adjacent soft tissue swelling with a variable degree of small joint synovitis. There is no evidence of enthesitis of the insertion of the flexor digitorum tendons and of the attachment of the capsule of the digit joints.
17304652 High CCL18/PARC expression in articular cartilage and synovial tissue of patients with rhe 2007 Feb OBJECTIVE: We studied the role of CCL18/pulmonary and activation-regulated chemokine (PARC) in rheumatoid arthritis (RA). METHODS: Human cartilage tissues and synovial membranes were obtained from patients with RA and with osteoarthritis (OA). Sera samples were obtained from RA patients, OA patients, healthy controls, and patients with flu, and synovial fluid (SF) from patients with RA and OA. Real-time PCR was performed with RNA from cartilage samples. Immunohistochemical analysis of CCL18/PARC was done with RA and OA cartilage and synovial tissue. Levels of CCL18/PARC in serum and SF were evaluated by ELISA. RESULTS: CCL18/PARC mRNA was expressed at significantly higher levels in RA cartilage than in OA (p = 0.0001) and control (p < 0.0001) samples. CCL18/PARC mRNA expression was much higher in RA synovial membrane than OA samples (p = 0.0001). All RA cartilage and synovial tissue samples exhibited medium to strong staining for CCL18/PARC. Serum levels of CCL18/PARC were higher in RA patients (156.21 +/- 125.73 ng/ml, n = 71) than in OA patients (64.54 +/- 40.90 ng/ml, n = 12) and controls (28.04 +/- 10.96 ng/ml, n = 20). Levels of CCL18/PARC in RA SF (275.20 +/- 228.16 ng/ml, n = 15) were higher than in OA (33.13 +/- 14.84 ng/ml, n = 6; p = 0.0198). CCL18/PARC levels correlated significantly with rheumatoid factor levels (r = 0.431, p = 0.0040), but not with matrix metalloproteinase-3, erythrocyte sedimentation rate, and C-reactive protein. CONCLUSION: CCL18/PARC was highly expressed in RA articular cartilage and synovial tissue compared with OA samples. Our data indicated that CCL18/PARC levels are not related to the conditions of generalized inflammation, but are related to the pathogenesis of RA.
17909386 Assessment of adherence to and persistence on disease-modifying antirheumatic drugs (DMARD 2007 Oct OBJECTIVE: Biologic disease-modifying antirheumatic drugs (DMARDs) are efficacious for treating rheumatoid arthritis (RA). However, measurements of relative effectiveness, including treatment adherence and persistence, are lacking. We evaluated adherence and persistence during new episodes of use of traditional and biologic DMARDs. METHODS: Using Tennessee Medicaid databases (1995-2004), we assembled a retrospective cohort of patients diagnosed with RA, and identified new episodes of use for 12 DMARD regimens. We evaluated persistence through survival analyses, and adherence within episodes through the medication possession ratio. A risk score was included in the analyses to account for measured confounders. RESULTS: We identified 14,932 patients with RA; 6018 patients had 10,547 episodes of new use of DMARDs. Considering methotrexate as the reference and after adjustment for measured confounders, episodes of new use of sulfasalazine [adjusted hazard ratio (aHR) = 1.59; 95% confidence interval (CI) = 1.47-1.72] and infliximab alone (aHR = 1.37, 95% CI = 1.09-1.73) were more likely to be discontinued; and new episodes of etanercept (aHR = 0.82, 95% CI = 0.73-0.92) and methotrexate + adalimumab (aHR = 0.63, 95% CI = 0.48-0.84) were less likely to be discontinued. Compared with methotrexate, adherence was higher for leflunomide, infliximab, etanercept, and adalimumab and lower for sulfasalazine and all combined therapies. CONCLUSIONS: We developed an approach to assess persistence on and adherence to the most common DMARD therapies. In this large cohort, persistence and adherence to leflunomide and most biologic DMARD therapies were at least comparable to methotrexate. Adherence was lower for sulfasalazine and all combined therapies.
17763852 Tumour necrosis factor a -308 promoter polymorphism in patients with rheumatoid arthritis. 2007 Dec There are controversial reports that TNF-a promoter polymorphism may be an independent marker of susceptibility to rheumatoid arthritis (RA). We used Polymerase chain reaction amplification and Restriction fragment length polymorphism for analysis of the polymorphism at position -308 in promoter of TNF-alpha gene in 34 patients with RA and 30 healthy individuals. Distribution of TNF-genotypes in RA patients did not differ from that in controls. Moreover, there was apparent association between the -308 TNF-alpha polymorphism and erosions in hand x-Ray was found (P value = 0.043). We suggest that TNF-alpha -308 promoter polymorphism is not a genetic risk factor for RA susceptibility but may be associated with radiographic damage in rheumatoid patients.
18725672 Midterm outcome of the Duracon total knee arthroplasty. 2008 Aug PURPOSE: To present midterm results of Duracon total knee arthroplasty (TKA) performed between 1991 and 2001. METHODS: One man and 43 women (65 knees) aged 46 to 84 (mean, 63) years who underwent primary TKAs using the Duracon prosthesis performed by a single surgeon were followed up for a mean of 8.5 (range, 5-11) years. All TKAs were cruciate-retaining and cemented, with only 9 of the patellae resurfaced. The diagnosis was osteoarthritis in 42 patients (61 knees), and rheumatoid arthritis in 2 patients (4 knees). Patients were assessed using the Knee Society Clinical Rating System, the Oxford Knee Score, and the Knee Society Total Knee Arthroplasty Roentgenographic Evaluation and Scoring System. RESULTS: The mean Knee Society knee score was 86 (range, 43-100) and the function score was 68 (0- 100). 94% of patients reported no or only mild pain. The mean Oxford Knee Score was 19. There was no patellofemoral complication, deep vein thrombosis or pulmonary embolism. Complications included a superficial infection and an uncontrolled deep infection. One patient had the insert exchanged for wear at the 11-year follow-up, and another had the polyethylene insert and tibial tray revised after a motorcycle accident. CONCLUSION: The Duracon TKA had good midterm clinical results with absence of patellofemoral complications.
17203297 Long-term benefit of radon spa therapy in the rehabilitation of rheumatoid arthritis: a ra 2007 Jun This study investigates the effects of radon (plus CO2) baths on RA in contrast to artificial CO2 baths in RA rehabilitation using a double-blinded trial enrolling 134 randomised patients of an in-patient rehabilitative programme (further 73 consecutive non-randomised patients are not reported here). The outcomes were limitations in occupational context/daily living (main outcome), pain, medication and further quantities. These were measured before the start, after the end of treatment and quarterly in the year thereafter. Repeated-measures analysis of covariance (RM-ANCOVA) of the intent-to-treat population was performed with group main effects (GME) and group x course interactions (G x C) reported. Hierarchically ordered hypotheses ensured the adherence of the nominal significance level. The superiority of the radon treatment was found regarding the main outcome (RM-ANCOVA until 12 months: p(GME) = 0.15, p(G x C) = 0.033). Consumption of steroids (p(GME) = 0.064, p(G x C) = 0.025) and NSAIDs (p(GME) = 0.035, p(G x C) = 0.008) were significantly reduced. The results suggest beneficial long-term effects of radon baths as adjunct to a multimodal rehabilitative treatment of RA.
16927578 Relationship of psychiatric history to pain reports in rheumatoid arthritis. 2006 OBJECTIVE: The purpose was to examine the relationship of pre-existing psychiatric history to pain reports in a cohort of persons with RA and concomitant major depression who were receiving a trial of antidepressant medication. METHOD: RA patients (n = 41) with a current episode of major depression were divided into two subgroups comprised of those with a previous psychiatric history (PSY+) (n = 20) and those without a previous psychiatric history (PSY-) (n = 21). The groups were compared with regard to their responsiveness to a regimen of antidepressive medication on measures of depression, pain, coping, and life stress over a period of 15 months. RESULTS: Although depression scores for both the PSY+ and the PSY- groups decreased significantly from baseline to 15-month follow-up, the composite pain score was found to be significantly decreased only for the PSY- group. CONCLUSION: Psychiatric history appears to predispose persons with concomitant RA and major depression to report less pain reduction following antidepressive treatment than those persons without a psychiatric history.
16510063 When should COX-2 selective NSAIDs be used for osteoarthritis and rheumatoid arthritis? 2006 Mar Cyclo-oxygenase-2 (COX-2) selective nonsteroidal anti-inflammatory drugs (NSAIDs) are as effective as acetaminophen and nonselective NSAIDs in treating of osteoarthritis, and are equally effective in reducing pain and inflammation and improving of joint function for patients with rheumatoid arthritis, when compared with nonselective NSAIDs. The COX-2 selective NSAIDs also have a better gastrointestinal safety profile in short-term (6-12 month) treatment (strength of recommendation [SOR]: A, based on meta-analysis of randomized controlled trials with patient-oriented outcomes). However, with recent growing concern of the cardiovascular safety of COX-2 selective NSAIDs, it is imperative to select appropriate patients by considering benefit vs risks, which include serious gastrointestinal bleeding, history of intolerance to nonselective NSAID, cardiovascular disease or associated risks, renal disease, patient's preference, and cost.
17117591 Drug evaluation: apratastat, a novel TACE/MMP inhibitor for rheumatoid arthritis. 2006 Nov Wyeth Research was developing apratastat (TMI-005), one in a series of dual TNFalpha-converting enzyme and matrix metalloprotease-13 inhibitors, for the potential treatment of inflammation, especially rheumatoid arthritis. By January 2005, apratastat had entered a phase II clinical trial; however, in October 2006, Wyeth reported that it had terminated development of the drug because of lack of efficacy in this trial.
16839616 Optimising stable retroviral transduction of primary human synovial fibroblasts. 2006 Oct Fibroblast like synoviocytes are the main resident cells in normal joints and are known to play a major role in the pathogenesis of rheumatoid arthritis. Efficient gene targeting of fibroblast like synoviocytes (FLS) is a major goal of current ex vivo gene therapy approaches for the treatment of rheumatoid arthritis. However, there is a need to improve viral systems capable of delivering genes to human rheumatoid fibroblasts and attempts have been made to develop a protocol for high efficiency, reproducible gene transfer using a replication-defective retrovirus vector. The effects of different experimental conditions were examined as well as those related to cellular and viral features on the efficiency of transducing the retroviral-driven expression of enhanced green fluorescent protein (EGFP) to FLS harvested from patients with rheumatoid arthritis. The optimal method established involved a double round of infection by centrifugation with a resting period of 4h between rounds. This approach led to the transduction of 30-70% of FLS obtained from nine patients with rheumatoid arthritis. Consistent transduction efficiencies were achieved in repeat assays such that it could be inferred that the variations observed were attributable to the specific characteristics of each cell line. This simple protocol renders a consistent and reproducible efficiency of rheumatoid fibroblast transduction and makes stable gene targeting using non-replicating retrovirus derived vectors an affordable option for the treatment of rheumatoid arthritis.