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ID PMID Title PublicationDate abstract
11885381 [Stability of the forearm after resection of the distal ulna and proximal radius in rheuma 2002 Jan Combined resection of radial head and distal ulna could jeopardize the stability and kinematics of the forearm bones. The goals of this retrospective study was to investigate these data after resection of distal ulna and proximal radius in rheumatoid arthritis. Between 1990 and 1998, eleven patients had these bone resections combined with implantation of elbow prostheses (eight Kudo and three GSB III). Wrist surgery consisted in five wrist arthrodeses combined with Darrach procedure, four Sauvé-Kapandji procedures and two isolated Darrach procedures. Mean age at surgery was 58 years and the average follow-up was 40 months. We assessed at follow-up: 1) wrist and elbow pain according to Gschwend; 2) stability of the forearm bones (cubitus valgus angle, impingement of the proximal radial stump with humerus, giving away accident of the ulnar distal stump); 3) wrist and elbow mobility. At follow-up six patients had no pain at the elbow and five had slight occasional pain. At the wrist, five patients had no pain and six slight occasional pain. Elbow motion was increased (from mean 83 degrees [50 degrees-100 degrees] to mean 110 degrees [85 degrees-135 degrees]) excepted in supination which slightly decreased (from mean 3 degrees [40 degrees-90 degrees] to mean 75 degrees [85 degrees-90 degrees]). Mean wrist mobility was impaired because of the five combined radiocarpal arthrodeses. If these five wrist arthrodeses were excluded, the mean ranges of motion were: 10 degrees in flexion, 16 degrees in extension, 2 degrees in radial deviation, 14 degrees in ulnar deviation. At follow-up, no patient had giving away accident of the ulnar distal stump nor impingement between radial stump and humerus in full flexion. Average cubitus valgus was 10 degrees. This study pointed out the predominant effect of the interosseous membrane in stability of the forearm bones.
12905464 Treatment of rheumatoid arthritis with tumor necrosis factor inhibitors may predispose to 2003 Aug OBJECTIVE: The long-term safety of therapeutic agents that neutralize tumor necrosis factor (TNF) is uncertain. Recent evidence based on spontaneous reporting shows an association with active tuberculosis (TB). We undertook this study to determine and describe the long-term safety of 2 of these agents, infliximab and etanercept, in rheumatic diseases based on a national active-surveillance system following the commercialization of the drugs. METHODS: We analyzed the safety data actively collected in the BIOBADASER (Base de Datos de Productos Biológicos de la Sociedad Española de Reumatología) database, which was launched in February 2000 by the Spanish Society of Rheumatology. For the estimation of TB risk, the annual incidence rate in patients treated with these agents was compared with the background rate and with the rate in a cohort of patients with rheumatoid arthritis (RA) assembled before the era of anti-TNF treatment. RESULTS: Seventy-one participating centers sent data on 1,578 treatments with infliximab (86%) or etanercept (14%) in 1,540 patients. Drug survival rates (reported as the cumulative percentage of patients still receiving medication) for infliximab and etanercept pooled together were 85% and 81% at 1 year and 2 years, respectively. Instances of discontinuation were essentially due to adverse events. Seventeen cases of TB were found in patients treated with infliximab. The estimated incidence of TB associated with infliximab in RA patients was 1,893 per 100,000 in the year 2000 and 1,113 per 100,000 in the year 2001. These findings represent a significant increased risk compared with background rates. In the first 5 months of 2002, after official guidelines were established for TB prevention in patients treated with biologics, only 1 new TB case was registered (in January). CONCLUSION: Therapy with infliximab is associated with an increased risk of active TB. Proper measures are needed to prevent and manage this adverse event.
14677018 A study on soluble intercellular adhesion molecule-1 and selenium in patients with rheumat 2003 Dec Clinical manifestations of vasculitis, as a complication of rheumatoid arthritis (RA), can be postulated as a consequence of immune response abnormalities and endothelial cell dysfunction. In this study we searched for the relationship between the extent of vascular involvement and either serum sICAM-1 or selenium concentrations. We also explored the possible interaction of serum selenium with sICAM-1 to provide a greater understanding of their role in rheumatoid vasculitis (RV). For the study, we measured the serum titers of sICAM-1 using an ELISA assay and the serum selenium concentrations using the ETAAS method in 37 women suffering from RA and 18 normal women serving as controls. All the RA patients were evaluated by extensive clinical, laboratory and capillaroscopic studies. In all patients with extra-articular manifestations, severe or moderate changes in nailfold capillaroscopy were found. Serum sICAM-1 titers in RA patients with mild vasculitis on nailfold capillaroscopy did not differ significantly from those of the healthy subjects, whereas a higher sICAM-1 level seemed to reflect the more intensive vascular changes in capillaroscopy. These data suggest that sICAM-1 serum levels may reflect the extent of the microvascular involvement in RA patients. Compared with controls, all the RA patients had markedly lower serum selenium concentrations, irrespective of the degree of the capillaroscopic vascular changes. A significant inverse correlation between sICAM-1 and selenium was found in the controls (r = -0.54; P<0.02). By contrast, no correlation was noted in RA patients (r=0.10, P not significant). This suggests that the sICAM-1 shedding in RV does not appear to be influenced by selenium, presumably owing to its low serum concentration.
11886960 Plasminogen activator inhibitor type-1 deficiency attenuates murine antigen-induced arthri 2002 Feb OBJECTIVE: To examine the role of plasminogen activator inhibitor type-1 (PAI-1), the major fibrinolytic inhibitor, in vivo during murine antigen-induced arthritis (AIA). METHODS: AIA was induced in PAI-1-deficient mice and control wild-type mice. Arthritis severity was evaluated by technetium 99m (99mTc) uptake in the knee joints and by histological scoring. Intra-articular fibrin deposition was examined by immunohistochemistry and synovial fibrinolysis quantitated by tissue D-dimer measurements and zymograms. RESULTS: Joint inflammation, quantitated by 99mTc uptake, was significantly reduced in PAI-1(-/-) mice on day 7 after arthritis onset (P<0.01). Likewise, synovial inflammation, evaluated by histological scoring, was significantly decreased in PAI-1-deficient mice on day 10 after arthritis onset (P<0.001). Articular cartilage damage was significantly decreased in PAI-1(-/-) mice, as shown by histological grading of safranin-O staining on day 10 after arthritis onset (P<0.005). Significantly decreased synovial accumulation of fibrin was observed by day 10 in arthritic joints of PAI-1(-/-) mice (P<0.005). Accordingly, the synovial tissue content of D-dimers, the specific fibrin degradation products generated by plasmin, were increased in PAI-1(-/-) mice (P<0.02). Finally, as expected, PA activity was increased in synovial tissues from PAI-1(-/-) mice, as shown by zymographic analysis. CONCLUSIONS: These results indicate that deficiency of PAI-1 results in increased synovial fibrinolysis, leading to reduced fibrin accumulation in arthritic joints and reduced severity of AIA.
15170903 The efficacy of leflunomide monotherapy in rheumatoid arthritis: towards the goals of dise 2004 Jun This expert review of results from the leflunomide phase II and III clinical trials database demonstrates that leflunomide meets all 3 goals desired of disease modifying antirheumatic drug (DMARD) therapy: reducing the signs and symptoms of the disease; inhibiting structural damage; and improving physical function. Further, leflunomide has a rapid onset of action, sustained efficacy, and is effective in early and late disease, regardless of whether patients have received other DMARD previously. The consistent efficacy of leflunomide across phase III clinical trials is confirmed by the findings from clinical practice. Experts agreed that it is important to observe a patient under leflunomide monotherapy for at least 3-4 months before assessing efficacy. It is possible to start maintenance therapy, with either a daily dose of leflunomide 10 mg, subsequently changing to 20 mg, or the reverse. The decision to use a loading dose when initiating leflunomide therapy depends primarily on the balance between the tolerability and rapid efficacy associated with a loading dose, and the balance desired for an individual patient. In general, the use of both maintenance and loading doses requires a flexible approach to the treatment of rheumatoid arthritis. During the first few weeks of leflunomide therapy, patient dropout can be avoided by using prednisolone rather than a loading dose. Moreover, to ensure good tolerability and compliance in patients receiving a loading dose, information and adequate support should be provided throughout treatment.
14989427 Anakinra as a new therapeutic option in rheumatoid arthritis: clinical results and perspec 2002 Sep Interleukin-1 receptor antagonist (IL-1Ra) is a member of the IL-1 gene family, which blocks IL-1-mediated signal transduction. In rheumatoid arthritis (RA), recombinant human IL-1Ra (anakinra) has been evaluated in 5 randomized, placebo-controlled clinical trials. In the European monotherapy study, 43% of patients receiving 150 mg/day anakinra achieved a 20% response according to the American College of Rheumatology criteria (ACR 20), compared to 27% in the placebo group. In the methotrexate combination therapy study, 42% of the patients receiving 1 mg/kg/day anakinra achieved an ACR20 response, 24% an ACR50 response, and 10% an ACR70 response. In each study, clinically meaningful improvements in the Health Assessment Questionnaire scores were observed. The Economic Resource Survey was employed in the European monotherapy study to evaluate patient and caregiver days of missed work or domestic activity in successive 4-week periods. There were rapid gains in the number of days at work or domestic activity in the treated patients, and the increases in productivity were dose-related. The mean change in the total modified Sharp score of patients who completed treatment with anakinra was significantly less than in the patients who received placebo. Anakinra, a new biologic approach to the treatment of RA, results in significant improvements in the signs and symptoms, has beneficial effects on functional status, and on the rate of progressive structural joint damage.
12879221 Preferential reductions of paraarticular trabecular bone component in ultradistal radius a 2003 Aug Rheumatoid arthritis (RA) is a major cause of secondary osteoporosis and is frequently associated with both paraarticular and generalized osteoporosis. The present study was designed to investigate the preferential sites of reduction of bone mineral density (BMD), in the early stage of RA, with special emphasis on the differential effect of RA on BMD in trabecular and cortical components. The participants (30 RA patients and 26 healthy participants) were all female with disease duration of less than 1 year. BMD in the radius was measured at 4% (ultradistal site) and 20% (midshaft) to the ulnar length proximal to the end of radius by peripheral quantitative computed tomography. BMD in lumbar spine was measured by dual X-ray absorptiometry and the osteo-sono assessment index (OSI) of the calcaneus by ultrasound. RA patients showed lower BMD preferentially in the trabecular component, but not in cortical bone component of the ultradistal radius than age-matched normal controls. Calcaneus OSI was also significantly reduced. The radial midshaft and lumbar spine did not differ significantly between RA patients and normal controls. Trabecular BMD in the ultradistal radius exhibited negative correlations with serum CRP, ESR, and RF, and calcaneus OSI with M-HAQ score. In conclusion, it was suggested that disease activity of RA and impairment of daily physical activity might be a significant determinant of deterioration of bone structure in paraartciular distal radius and calcaneus, respectively, in early-stage RA patients.
12114307 Carotid atherosclerosis in patients with rheumatoid arthritis: a preliminary case-control 2002 Jun A preliminary study was undertaken to investigate the severity of atherosclerotic lesions of neck arteries in patients with rheumatoid arthritis (RA) in comparison with matched controls. The working hypothesis derives from the recent view that the atherosclerotic plaque is essentially an inflammatory lesion. Thus, patients affected by a chronic inflammatory disease, such as RA, might show acceleration of atherosclerosis despite treatment with anti-inflammatory drugs. In 19 patients with RA the prevalence of atherosclerosis of internal carotid arteries, as seen on high-resolution duplex-scanning of neck arteries, was significantly (p < 0.05) higher than in 19 controls, whereas no significant difference was found for the other arteries. Factors underlying this finding are not known; increased levels of homocysteine and other thiol compounds that may enhance atherosclerosis in RA patients deserve further investigation. Moreover, more specific factors of RA are currently being investigated. In fact, immune complexes fixing C1q bind to endothelial receptors, thus triggering an upregulation of adhesion molecules, such as E-selectin and intercellular and vascular cell adhesion molecules 1, on the endothelium surface.
11841066 Beyond disability: perceived participation in people with a chronic disabling condition. 2002 Feb OBJECTIVE: To describe the impact of a chronic disabling condition on participation and to identify variables that may explain perceived restrictions in participation. STUDY DESIGN: Cross-sectional. SETTING: People were recruited from the outpatient clinics of two rehabilitation centres and the rehabilitation department of an academic hospital. SUBJECTS: One hundred and twenty-six people from five diagnostic groups (neuromuscular disease, rheumatoid arthritis, spinal cord injury, stroke, fibromyalgia) participated in the study. METHOD: The IPA (Impact on Participation and Autonomy) questionnaire was used to describe perceived participation. Explanatory variables were studied in terms of sociodemographic factors and health status variables. RESULTS: Some restrictions in participation seem comparable among diagnostic groups, others are specific to one or two groups. People with stroke, rheumatoid arthritis or fibromyalgia perceived more restrictions in participation than people with spinal cord injury or neuromuscular disorders. Emotional distress was the most important factor contributing to restrictions in participation. CONCLUSIONS: Perceived participation remains a complex concept in which many factors are involved. To make a contribution to meaningful participation of people with a chronic disabling condition, rehabilitation treatment should address physical, social, emotional and environmental aspects.
12860726 Extra-articular disease manifestations in rheumatoid arthritis: incidence trends and risk 2003 Aug OBJECTIVE: To investigate the trends in incidence of extra-articular rheumatoid arthritis (ExRA) in a well defined community based cohort of patients with rheumatoid arthritis (RA), and to examine possible predictors of ExRA occurrence. METHODS: Using the resources of the Rochester Epidemiology Project, a retrospective medical record review was conducted of a cohort of 609 cases of RA in Olmsted County, MN, diagnosed during 1955-94. These cases had been previously classified using the ACR 1987 criteria for RA. Patients were followed up from 1955 to 2000 (median follow up 11.8 years; range 0.1-42.8), and incident ExRA manifestations were recorded according to predefined criteria. Time to first presentation of ExRA was compared in patients with RA by decade of diagnosis. Possible ExRA risk factors were identified in case record reviews. RESULTS: ExRA occurred in 247 patients (40.6%). A subgroup of 78 patients (12.8%) had ExRA manifestations considered to be severe in a previous study from Malmö, Sweden. The incidence of severe ExRA did not change significantly over the decades (p=0.165). In a multivariate analysis the main predictors of severe ExRA were smoking at RA diagnosis (risk ratio (RR)=2.94; 95% confidence interval (95% CI) 1.68 to 5.13) and early disability (Steinbrocker class III-IV at diagnosis) (RR=2.45; 95% CI 1.51 to 4.00). The effect of smoking overwhelmed the weaker effect of rheumatoid factor seropositivity. CONCLUSION: There was no decrease in the incidence of extra-articular manifestations in patients with RA diagnosed up to 1995. Smoking and early disability are independent risk factors for extra-articular RA.
12096222 Methotrexate in the treatment of rheumatoid arthritis. II. In vivo effects on bone mineral 2002 Jul OBJECTIVE: To determine the effect of methotrexate (MTX) on bone mineral density (BMD) in rheumatoid arthritis (RA). METHODS: One hundred and sixteen non-steroid-treated RA subjects (90 women) were studied in a prospective, longitudinal, non-randomized study. Subjects started MTX (n=36) or sulphasalazine (n=23) or continued long-term (>5 yr) treatment with MTX (n=28) or other disease-modifying anti-rheumatic drugs (n=29). BMD was estimated at entry and after 1 yr. Markers of bone turnover were measured at entry and at 1 yr, and additionally at 3 and 6 months in those starting treatment. Bone biopsies were taken before and after MTX treatment in four subjects. The primary outcome was change in BMD Z score and secondary outcomes were changes in bone turnover markers and bone formation by histomorphometry. RESULTS: Univariate analysis of covariance found that MTX at baseline was associated with reduced BMD at the femoral neck. However, femoral neck BMD was also associated with radiological damage score for the hand. Multivariate analysis and discriminant analysis of the subset of post-menopausal women showed that reduced bone density associated with MTX was due to confounders such as disease activity. There was no adverse effect of MTX on bone turnover markers or on measures of bone formation in biopsies. CONCLUSIONS: No adverse effect of low-dose MTX (mean 10 mg/week) on bone formation in RA was found.
12008859 Efficacy of anakinra in bone: comparison to other biologics. 2002 Jan Three biologic therapies significantly slow radiographic progression in active rheumatoid arthritis. This paper compares the effects of anakinra, a recombinant human interleukin-1 receptor antagonist, with those of etanercept and infliximab, two drugs that target tumor necrosis factor-alpha. A Medline search identified controlled clinical trials that included radiographic progression as an endpoint. Anakinra 30 to 150 mg subcutaneously each day for 24 weeks was significantly more effective than placebo in slowing progression of erosion, joint-space narrowing, and total composite scores, as assessed by the Genant method, and erosive joint count, as assessed by the Larsen method. Erosion scores were slowed even further during a 24-week extension. Etanercept 25 mg subcutaneously twice weekly and infliximab 3 to 10 mg/kg intravenously every 4 or 8 weeks also slowed progressive joint damage, but these agents were studied under different study designs, patient populations, and radiographic assessments than those used in the anakinra study. Despite these differences, however, each biologic therapy appeared to slow progressive joint damage. In some studies, control of clinical symptoms did not correlate with slowing of radiographic progression. Agents that block interleukin-1 or tumor necrosis factor-alpha appear similarly effective in slowing radiographic progression in patients with active rheumatoid arthritis. Treatment strategies for this disease may need to consider clinical symptoms, progressive joint damage, and long-term safety effects separately.
12006324 Predictors of progression of HRCT diagnosed fibrosing alveolitis in patients with rheumato 2002 Jun BACKGROUND: Fibrosing alveolitis (FA) is the most serious pleuropulmonary extra-articular feature of rheumatoid arthritis (RA). Features that predict progression of FA in patients with RA have not yet been determined. OBJECTIVE: To identify clinical features that predict progressive FA in patients with RA. METHODS: An unselected cohort of 29 patients with RA and FA confirmed by high resolution computed tomography (HRCT) were studied prospectively for 24 months. Three monthly clinical assessment, four monthly pulmonary function tests, and yearly HRCT scanning was undertaken on these patients. Progressive FA was defined as >15% fall in carbon monoxide transfer factor (TLCO) with evidence of increasing FA on HRCT or death as a result of FA. RESULTS: During 24 months of follow up 10/29 (34%) patients had progressive FA. Progression on HRCT was seen as acute ground glass exacerbations or increasing reticular pattern lung involvement. Progressive FA was associated with the presence of bibasal crackles (p=0.041), TLCO (p=0.001), and extent (p=0.026) and distribution (p=0.031) of lung involvement on HRCT at initial presentation. When multiple logistic regression was used, only TLCO remained significant. Receiver operator curve analysis was employed to identify presenting TLCO of progressive FA. A TLCO <54% of the predicted value demonstrated 80% sensitivity and 93% specificity in predicting progressive FA. CONCLUSIONS: A TLCO <54% of the predicted value is a highly specific predictor of disease progression.
12006318 Identification of the advanced glycation end products N(epsilon)-carboxymethyllysine in th 2002 Jun BACKGROUND: Generation of advanced glycation end products (AGEs) is an inevitable process in vivo and can be accelerated under pathological conditions such as oxidative stress. In serum and synovial fluid of patients with rheumatoid arthritis (RA) raised AGE levels have been found. OBJECTIVE: To determine the presence of N(epsilon)-carboxymethyllysine (CML; marker of oxidative stress) in RA synovial tissue by immunohistology. METHODS: Frozen synovial tissue samples from 10 patients with RA and eight controls (four patients without joint disease and four patients with osteoarthritis (OA)) were treated with rabbit-anti-CML-IgG and goat-antirabbit-IgG. Immunostaining was visualised by streptavidine-alkaline phosphatase (chromogen fuchsin). Cell differentiation was performed with antibodies against CD68, CD45RO, and CD20. RESULTS: CML was detected in the synovial lining, sublining, and endothelium in 10/10 RA and 4/4 OA synovial specimens. In RA some macrophages (CD68+) and T cells (CD45RO+) showed positive immunostaining for CML, whereas B cells were negative. Staining in OA synovial sublining was weak compared with RA. CONCLUSIONS: CML was detected for the first time in RA and OA synovial tissue. Different patterns of immunostaining in RA and OA and the presence of CML on macrophages and T cells, suggest a role for CML in the pathogenesis of RA. This might be due to presentation of new epitopes which can maintain or even trigger an autoimmune response.
15077267 Physical activity behavior in older women with rheumatoid arthritis. 2004 Apr 15 OBJECTIVE: To identify physical activity behaviors of older (>/=60 years) women with rheumatoid arthritis, and to determine if physical activity behavior differed by demographic characteristics or disease duration. METHODS: Cognitively intact, ambulatory women with rheumatoid arthritis seen at an urban university arthritis center (n = 185) responded to a survey that included demographics, number of years since RA diagnosis, and physical activity assessed with the Yale Physical Activity Survey. RESULTS: Participants had a mean age of 70 years and a mean disease duration of 17.6 years. Mean total of physical activity, including low-, moderate-, and high-intensity activity, was 23 hours/week, with 47 different physical activities identified. Housework comprised 67% of total physical activity time, whereas leisure activities and planned exercise comprised only 15% and 10%, respectively. Sixty percent of the women reported participation in some type of vigorous activity, and 88% reported they had done leisure walking in the past month. Age was negatively associated with scores on the activity summary index (r = -0.195, P < 0.01), and there was a significant difference on the activity summary index by employment status, with women in the work force (n = 47) and those involved in housekeeping (n = 105) scoring significantly higher (P = 0.003) than the women (n = 33) who described themselves as retired (F = 7.81, 2 degrees of freedom, P = 0.001). CONCLUSION: Older women with rheumatoid arthritis may participate in a broader array of physical activities than previously assumed, and could benefit from increasing the proportion of moderate or vigorous activity incorporated into their daily routines.
12831364 Gene transfer as a future therapy for rheumatoid arthritis. 2003 Jul Inhibiting key pathogenic processes within the rheumatoid synovium is a most attractive goal to achieve, and the number of potential intra- and extracellular pathways operative in rheumatoid arthritis (RA) that could be used for a gene therapy strategy is increasing continuously. Gene transfer or gene therapy might also be one of the approaches to solve the problem of long-term expression of therapeutic genes, in order to replace the frequent application of recombinant proteins, in the future. However, at present, gene therapy has not reached a realistic clinical stage, which is mainly due to severe side effects in humans, the complexity of RA pathophysiology and the current state of available gene transfer techniques. On the other hand, novel gene delivery systems are not restricted to vectors or certain types of cells, as mobile cells including macrophages, dendritic cells, lymphocytes and multipotent stem cells can also be used as smart gene transfer vehicles. Moreover, the observation in animal models that application of viral vectors into a joint can exert additional therapeutic effects in nearby joints might also facilitate the transfer from animal to human gene therapy. Future strategies will also examine the potential of novel long-term expression vectors such as lentiviruses and cytomegalovirus (CMV)-based viruses as a basis for future clinical trials in RA.
12175100 Down regulation of glucocorticoid receptors in early-diagnosed rheumatoid arthritis. 2002 Jul OBJECTIVE: In patients with rheumatoid arthritis (RA) of longer duration, glucocorticoid receptor (GR) down-regulation has been reported without any change in cortisol levels. This phenomenon might play a role in the aetio-pathogenesis of RA. Therefore we studied GR expression, as well as the serum cortisol levels, in patients with recently diagnosed RA. METHODS: In 81 early diagnosed RA patients with disease duration < 1 year (52F/29M; mean (SD) age 63 (13) years) and in 39 age and sex matched controls (23F/16M; mean age 63 (15) years) blood samples were taken between 8-10 h AM. GR expression (GR-number and GR-affinity), serum cortisol levels, ESR, CRP, painful and swollen joints were measured. RESULTS: A significantly lower GR-number was found in the female patients compared with female controls: 7.0 versus 9.8fmol/million cells, respectively (difference: 2.8, 95% CI 1.1 - 4.6). Interestingly, also serum cortisol levels were significantly lower in the female patients compared with the female controls: 0.21 versus 0.41 micromol/l, respectively (difference: 0.20, 95% CI 0.12 - 0.28). However, between the male patients and male controls no difference was found in GR expression nor in serum cortisol levels. Neither in female nor in male patients were correlations found between GR expression and parameters of disease activity nor was there a relation between GR expression and serum cortisol levels. CONCLUSIONS: Changes in GR expression as well as serum cortisol were not a general phenomenon in early diagnosed RA patients, being present only in females and not related to disease activity. Therefore it seems unlikely that GR expression per se is causally involved in the pathogenesis of RA. We cannot preclude that it may be involved in the incidence, severity and course of RA, as this may be differentially regulated in males and females.
12114259 Glucocorticoid receptor downregulation in early diagnosed rheumatoid arthritis. 2002 Jun In patients with rheumatoid arthritis (RA) with a mean duration of six years, glucocorticoid receptor (GR) downregulation has been reported without change in cortisol levels. This phenomenon might play a role in the etiopathogenesis of RA. If this is the case, GR downregulation should also be found in early-diagnosed RA. We compared GR expression and cortisol levels of early RA patients with those of sex and age matched healthy controls. In early (disease duration less than one year) RA patients (52F/29M; mean [SE] age 63 +/- 2 years) and in 39 controls (23F/16M; mean age 63 +/- 2 years) blood samples were taken between 8:00 and 10:00 a.m. GR expression (GR number), cortisol levels (fluorescence polarization immunoassay, FPIA), ESR, CRP, and the presence of swollen and painful knees were determined. RA was diagnosed according to the ACR classification criteria. In early RA a significantly lower GR expression was found compared to controls. Interestingly, cortisol levels were also significantly lower. Both findings were due to the observed differences in the female population. In the male population no differences were found. No correlations were found among parameters of disease activity, nor was there a relation between GR expression and serum cortisol levels. In female patients with early-diagnosed RA a decrease in glucocorticoid receptor expression was found as well as a decrease in cortisol levels. Since normal glucocorticoid receptor expression was found in the male population with early-diagnosed RA, it remains questionable if glucocorticoid receptor expression is causally involved in pathogenesis of RA.
15380032 Gene therapy in animal models of rheumatoid arthritis: are we ready for the patients? 2004 Rheumatoid arthritis (RA) is a chronic inflammatory disease of the synovial joints, with progressive destruction of cartilage and bone. Anti-tumour necrosis factor-alpha therapies (e.g. soluble tumour necrosis factor receptors) ameliorate disease in 60-70% of patients with RA. However, the need for repeated systemic administration of relatively high doses in order to achieve constant therapeutic levels in the joints, and the reported side effects are downsides to this systemic approach. Several gene therapeutic approaches have been developed to ameliorate disease in animal models of arthritis either by restoring the cytokine balance or by genetic synovectomy. In this review we summarize strategies to improve transduction of synovial cells, to achieve stable transgene expression using integrating viruses such as adeno-associated viruses, and to achieve transcriptionally regulated expression so that drug release can meet the variable demands imposed by the intermittent course of RA. Evidence from animal models convincingly supports the application of gene therapy in RA, and the feasibility of gene therapy was recently demonstrated in phase I clinical trials.
12810213 Magnetic resonance imaging in the assessment of synovial inflammation of the hindfoot in p 2003 Jul OBJECTIVES: To describe the localisation of synovitis and tenosynovitis of the hindfoot observed on magnetic resonance imaging (MRI) in patients with chronic polyarthritis, and to correlate the findings of physical examination and MRI. METHODS: Patients with chronic polyarthritis, and one or two painful hindfoot were included. On physical examination and on MRI, the tibio-talar, talo-calcaneal, and talo-navicular and calcaneo-cuboidal joints were adjudged to have or not synovitis, and the tibialis anterior and posterior, the peroneus longus and brevis, the flector digitorum and hallucis longus tendons to have or not tenosynovitis. Criteria for synovitis and tenosynovitis were a high signal intensity on T2-weighted images, a low signal intensity on T1-weighted images, and enhancement after Gd-DTPA injection, in the joint area, and around the tendon, respectively. The correlation between the findings of physical examination and those of MRI were evaluated using the Kappa statistics. RESULTS: 12 patients (three men, nine women, mean age of 55.5 years+/-11.4 S.D.) with chronic polyarthritis (rheumatoid arthritis (RA): nine, ankylosing spondylitis: one; psoriatic arthritis: one, unclassified: one) were included. All presented with one (7 patients) or two (5 patients) painful hindfeet (and swelling for 16 out of 17 hindfeet). On physical examination, 25 joints and eight tendons were adjudged to have synovitis and tenosynovitis. MRI showed synovitis in 12 out of 25 of these joints (48%), and tenosynovotis in three out of eight of these tendons (37.5%). Moreover, MRI showed ten and seven clinically unsuspected synovitis and tenosynovitis, respectively. The proportion of agreements between physical examination and MRI were 54.9% (kappa=0.1) and 88.2% (kappa=0.27) for synovitis and tenosynovitis, respectively. CONCLUSION: A weak correlation was observed between the findings of physical examination and MRI in patients with chronic polyarthritis and a painful hindfoot. MRI might be used to localise synovitis in the area before performing some intra-articular injections. However, other studies are needed to address this question.