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Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
18058095 Changes underlying the dynamic contrast-enhanced MRI response to treatment in rheumatoid a 2008 Mar OBJECTIVE: Dynamic contrast-enhanced MRI of patients with rheumatoid arthritis has shown a decrease in the early enhancement rate (EER) of synovitis after treatment. The purpose of this work was to investigate the underlying changes. METHODS: 3D dynamic contrast-enhanced images were acquired from 13 patients before and 1-2 weeks after anti-TNF alpha treatment. The EER of the inflamed synovium was measured. The T1 relaxation time of the synovitis was calculated from images at different flip angles. The time course of the arrival of gadolinium at the radial artery was determined. The gadolinium enhancement of the inflamed synovium was modeled to calculate the fractional plasma volume (vp), the fractional extravascular, extracellular fluid volume (ve), and the volume transfer constant (Ktrans). Pre- and post-treatment values were compared and the dependence of the EER on each parameter was assessed. RESULTS: There was a decrease in the EER measured over 26 s after treatment (29%, p = 0.002). Reductions in T1 (12%, p = 0.001), Ktrans (31%, p = 0.002), and vp (43%, p = 0.01) contributed to this; however, the EER was relatively insensitive to changes in ve. CONCLUSIONS: The decrease in EER after anti-TNF alpha treatment is largely caused by reductions in the volume transfer constant Ktrans, the fractional plasma volume vp, and the T1 relaxation time. Only the contributions from Ktrans and vp directly reflect synovial vascularity.
16897197 Relation between atlantoaxial (C1/2) and cervical alignment (C2-C7) angles with Magerl and 2006 Jul BACKGROUND: A few studies have reported the relation between the atlantoaxial (C1/2) angle and cervical alignment (C2-C7) angle after a Magerl and Brooks (M&B) surgical procedure to treat atlantoaxial subluxation (AAS) in patients with rheumatoid arthritis (RA). However, no study has examined an optimum preoperative C1/2 angle reduction. We aimed to assess the relation between the C1/2 angle reduction and the C2-C7 angle change in patients with progressive RA who underwent the M&B procedure. METHODS: We retrospectively analyzed the relation between the preoperative C1/2 angle and C2-C7 angle in 28 consecutive RA patients using their clinical and radiological data. Differences in the preoperative and postoperative C1/2 and C2-C7 angles were detected. Correlations of these angles and the reduced degree of angles were examined. The Ranawat grading scale and Japanese Orthopaedic Association (JOA) scores were used to determine myelopathy. Pain was categorized into five categories according to severity. Clinical and X-ray evaluations were collected before surgery, at 3 and/or 6 months after surgery, and at final follow-up. RESULTS: Clinical symptoms, Ranawat grade, and JOA scores improved postoperatively, and patients achieved bony union within 3 months. We observed a strong and significant correlation between the reduced C1/2 angle and the change in the C2-C7 angle. Patients with a preoperative C1/2 angle of <20 degrees had markedly reduced cervical lordotic angle but this condition was not seen in patients with a preoperative C1/2 angle of >or=20 degrees . The optimum C1/2 angle was estimated as [20 degrees - (preoperative C1/2 angle)] in patients with a C1/2 angle <20 degrees or as an in situ angle in patients with a C1/2 angle of >or=20 degrees . CONCLUSIONS: Surgeons performing the M&B procedure need to select patients carefully and avoid complete or overreduction of the C1/2 angle to prevent serious postoperative SAS and myelopathy.
18975366 Is health equity considered in systematic reviews of the Cochrane Musculoskeletal Group? 2008 Nov 15 OBJECTIVE: To determine whether Cochrane Musculoskeletal Group (CMSG) systematic reviews and corresponding primary studies of rheumatoid arthritis interventions report and analyze the data needed to assess the effectiveness of interventions in reducing socioeconomic differences in health and/or improving the health of the poor. METHODS: We selected all CMSG reviews on rheumatoid arthritis published since issue 1, 2003. Fourteen reviews were identified; 147 of the 156 primary studies included in these reviews were obtained and assessed. We extracted data on whether the dimensions place of residence, race/ethnicity/culture, occupation, gender, religion, education, socioeconomic status, and social capital and networks (PROGRESS) were reported or analyzed, and whether any interventions were aimed at disadvantaged or low- and middle-income country populations. RESULTS: Among the dimensions of PROGRESS reported at baseline in 147 primary studies, gender (89%) was the most commonly reported, followed by education (25%) and race/ethnicity (18%). Less than 50% of the systematic reviews reported dimensions of PROGRESS even when they had been reported in the primary study. Of 147 primary studies, 6 (5%) were aimed specifically at disadvantaged populations; another 6 reported on effectiveness by at least 1 dimension of PROGRESS. CONCLUSION: Primary studies of interventions for rheumatoid arthritis generally reported few variables necessary to answer questions about health inequalities. Most CMSG systematic reviews failed to assess those variables even when described in the primary studies. The Cochrane Health Equity Field welcomes the opportunity to provide guidance to systematic review authors on incorporating equity considerations into their reviews.
18278522 [Somatostatin - an important inhibitor of neuronal activity]. 2008 Aug Many neuropeptides are involved in the processing of painful stimuli but a peptide of particular interest is somatostatin ("somatotropin release-inhibiting factor", SRIF). The physiological effects of SRIF are mediated by five SRIF receptors (sst receptors) which belong to the family of G protein-coupled receptors. All sst receptors inhibit the adenylate cyclase and open K(+)-channels, which leads to a decrease of neuronal excitability and decreases the secretion of neuropeptides or hormones. Many animal experimental data show that activation of sst receptors leads to a reduction of pain behaviour. Because SRIF also reduces important immune functions its effects on chronic inflammatory diseases, for example rheumatoid arthritis, have been extensively examined. Because SRIF only has a very short half-life, many SRIF analogues were synthesized. The first clinical study which documents an effectiveness of octreotide in the therapy of rheumatoid arthritis showed that this peptide has a significant therapeutic potential and opens new possibilities for the reduction of pain and inflammation.
17075825 Increased serum levels of soluble fractalkine (CX3CL1) correlate with disease activity in 2006 Nov OBJECTIVE: To determine levels of soluble fractalkine (sFkn) in rheumatoid arthritis (RA) patients with and without rheumatoid vasculitis (RV), and to assess the relationship of sFkn levels to disease activity. METHODS: Serum was obtained from 98 RA patients (54 without vasculitis, 36 with extraarticular manifestations but without histologically proven vasculitis, and 8 with histologically proven vasculitis) and from 38 healthy individuals. Levels of sFkn were measured by enzyme-linked immunosorbent assay. Expression of Fkn and CX(3)CR1 was quantified by real-time polymerase chain reaction. Vasculitis disease activity was assessed using the Birmingham Vasculitis Activity Score and the Vasculitis Activity Index. RESULTS: Serum sFkn levels were significantly higher in patients with RA than in controls and were significantly higher in RA patients with RV than in those without vasculitic complications. Statistically significant correlations were observed between serum sFkn levels in RA patients and levels of C-reactive protein, rheumatoid factor, immune complex, and complement. In the RV group, sFkn levels also correlated with disease activity. Immunohistochemical analysis indicated that Fkn levels were associated mainly with endothelial cells in vasculitic arteries. In addition, expression of CX(3)CR1 messenger RNA was significantly greater in peripheral blood mononuclear cells from patients with active RV than in those from other RA patients or controls. Notably, serum sFkn levels were significantly diminished following successful treatment and clinical improvement. CONCLUSION: These findings suggest that Fkn and CX(3)CR1 play crucial roles in the pathogenesis of RV and that sFkn may serve as a serologic inflammatory marker of disease activity in RA patients with vasculitis.
17233911 Novel dexamethasone-HPMA copolymer conjugate and its potential application in treatment of 2007 Rheumatoid arthritis (RA) is a chronic autoimmune disease of unknown etiology. Effective treatment of this disorder has been hampered by the lack of availability of agents that selectively target affected joint tissue. We developed a novel pH-sensitive drug delivery system of dexamethasone (Dex) based on an N-(2-hydroxypropyl)methacrylamide copolymer (P-Dex) and have shown that the delivery system specifically accumulates in inflamed joints in an animal model of arthritis. We hypothesize that the arthrotropism of the delivery system and the local acidosis-mediated drug release provide superior therapeutic efficacy and potentially reduced side effects in RA treatment. The initial in vitro drug-release study confirmed that the Dex release is indeed dependent upon the environmental pH. At pH 5, 37 degrees C, the conjugate shows the highest level of drug release. When administered systemically in an adjuvant-induced arthritis rat model, P-Dex offers superior and longer-lasting anti-inflammatory effects compared with systemically administered free Dex. In addition, greater bone and cartilage preservation was observed with the P-Dex treatment compared with free Dex treatment. Our data indicate that the differential effect of the conjugate is related to its selective accumulation, potential macrophage-mediated retention, and pH-sensitive drug release (extracellular and intracellular) in arthritic joints. This newly developed drug delivery system provides a unique method for selective targeting of glucocorticoids to inflamed joints which may potentially reduce systemic side effects.
18782791 Is the blood B-cell subset profile diagnostic for Sjogren syndrome? 2009 Sep OBJECTIVE: To evaluate the relevance of the blood B-cell subset profile for the diagnosis of Sjögren syndrome. METHODS: The distribution of mature blood B cells from Bm1 through Bm5 was determined in 161 patients, of whom 25 fulfilled the American-European Consensus Group criteria for primary SS (pSS), and 136 served as disease controls. RESULTS: The percentage of Bm2 and Bm2' cells was increased in the patients with pSS compared with 54 patients with rheumatoid arthritis (RA) and 18 with systemic lupus erythematosus (SLE) (p<0.001 for the two comparisons). In contrast, those of early Bm5 (eBm5) and Bm5 were decreased in patients with pSS, compared with patients with RA and with SLE (p<0.001 for the two comparisons). The receiver operating characteristic curves allowed for an optimising cut-off value of Bm2+Bm2' cells at 71.1% for 88.0% sensitivity and 83.1% specificity, that of eBm5+Bm5 cells at < or =13.5% for 84.0% sensitivity and 83.1% specificity, and, consequently, that of Bm2+Bm2'/eBm5+Bm5 at > or =5 for 88.0% sensitivity and 84.6% specificity. CONCLUSION: Given its presentation as a signature for pSS, relative to RA and SLE, such a distribution of B-cell subsets might provide a useful diagnostic tool.
17426360 Increased prevalence of anti-third generation cyclic citrullinated peptide antibodies in p 2007 Feb To investigate the prevalence of anti-third generation cyclic citrullinated peptide antibodies (anti-CCP3) in patients with systemic connective tissue diseases, we assembled a training set consisting of 115 patients with rheumatoid arthritis (RA), 52 with Calcinosis, Raynaud's phenomenon, oesophageal dysmotility, sclerodactyly, telangiectasia (CREST) syndrome, 21 with scleroderma, 20 with ankylosing spondylitis, 18 with reactive arthritis, 25 with juvenile rheumatoid arthritis (RA), 51 with osteoarthritis, 26 with mixed connective tissue disease, 23 with primary Sjogren's syndrome, 74 with systemic lupus erythematosus, 49 with Polymyalgia rheumatica, and 39 with polymyositis/dermatomyositis. The commercial enzyme-linked immunosorbent assay (ELISA) was used to detect anti-CCP antibodies, including anti-CCP2 (regular, second generation of CCP antigen) and anti-CCP3 (third generation of CCP antigen) in disease-related specimens and normal controls. These serum samples were also evaluated for anti-centomere antibodies by anti-centromere ELISA kit. The higher frequencies of anti-CCP3 and anti-CCP2 were detected in 75.6 and 70.4% patients with RA, respectively. At the same time, anti-CCP3 (not anti-CCP2) was significantly increased in samples isolated from patients with CREST syndrome. The clinical sensitivity of IgG anti-CCP3 for the patients with CREST syndrome was 29% (15 of 52) and the specificity was 96% (384 of 397), with the exception of the RA group. The anti-centromere antibodies were significantly higher in patients with CREST only. The results of our study suggest that compared to anti-CCP2 assay, the new anti-CCP3 assay can enhance the clinical sensitivity for diagnosis of RA and, as an associate marker combined with anticentromere, can distinguish CREST syndrome from other systemic connective tissue diseases, especially RA. The clinical specificity of anti-CCP3 was lower than anti-CCP2 assay in diagnosis of RA because of the crossreaction to the patients with CREST syndrome.
17894003 Cartilage oligomeric matrix protein level in rheumatic diseases: potential use as a marker 2007 Jun Cartilage oligomeric matrix protein (COMP) is a tissue-specific noncollagenous protein that was first detected in the serum and the synovial fluid of patients suffering from rheumatic disorders, such as rheumatoid arthritis, reactive arthritis, juvenile chronic arthritis, and osteoarthritis. In this review, the authors consider serum COMP levels in different diseases and discuss their study of patients with rheumatoid arthritis treated with anti-TNF-alpha, to evaluate whether COMP is able to predict a rapid and sustained clinical response to these drugs. They observe that patients with high COMP levels have a lower ACR 70 response independently of the state of systemic inflammation, and conclude that COMP seems to have a pathogenetic role that is independent of the mechanisms regulating inflammatory processes.
16437446 Intra-articular steroids and splints/rest for children with juvenile idiopathic arthritis 2006 Jan 25 BACKGROUND: Resting or immobilizing a joint to enhance outcomes following intra-articular (IA) steroid injection is generally advocated. This systematic review aimed to determine the efficacy of IA steroid injections and the influence of post-injection rest. OBJECTIVES: 1. Compare IA steroid injections versus no treatment or placebo. 2. Determine the effects of rest following IA steroid injection in rheumatoid or juvenile idiopathic arthritis. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (CENTRAL- Issue 4, 2003), Cochrane Database of Systematic Reviews (CDSR - Issue 4, 2003), Database of Abstracts of Reviews of Effectiveness (DARE - searched 8.1.04), MEDLINE (1966 to August Week 2 2004), EMBASE (1980 to August Week 2 2004) , CINAHL (1982 to December Week 2 2003), Clinical Trials site of the National Institute of Health, (USA - searched 8.1.04), OTseeker (Occupational Therapy Systematic Evaluation of Evidence - searched 8.1.04) and PEDro (Physiotherapy Evidence Database - searched 8.1.04) were searched. Journals and reference lists were hand searched. SELECTION CRITERIA: Eligible were randomised controlled trials of IA steroid injections or of rest following IA steroid injections in rheumatoid or juvenile idiopathic arthritis. DATA COLLECTION AND ANALYSIS: Potentially relevant references were evaluated and all data extracted by two independent reviewers. MAIN RESULTS: Five trials (n=346) examining IA steroid injection in the knee joint were included. It was not possible to pool data as outcome measures, timing of follow up and the methods of data reporting differed between trials. There was inconclusive conflicting evidence from two trials that walking time was reduced. There was evidence from one moderate quality trial that pain was reduced at 1-day post-injection (0-100 VAS from 28.33 to 13.46; McGill Pain Scale from 8.89 to 3.96) but not at 1 week or 7-12 weeks post-injection. There is some evidence that IA injections improved knee flexion (by 14 degrees) and reduced knee extension lag (by 20 degrees), knee circumference (median reduction = 0.3 cm) and morning stiffness (reduced from 60 mins to 7.6 mins). One trial (n=91) examined the effects of rest following injection in the knee. The rested group achieved significant improvement in pain, stiffness, knee circumference, and walking time when compared with the non-rested group (no point estimates provided). One trial evaluated rest following injection of the wrist (n=117). Relapse rate was higher in the rested group (rest relapse rate = 24/58, no-rest group = 14/59); but there were no differences between the rested and non-rested groups on pain, joint circumference, wrist function, grip strength or ROM. AUTHORS' CONCLUSIONS: There is some evidence to support the use of IA steroid injections and resting a knee following injections but that wrists should not be rested following injections. The included studies involved adult participants so any conclusions can only cautiously applied to children. Further research is required to examine the use and type of rest and the differential responses of different joints following injections.
17642235 [Humanized anti-human IL-6 receptor antibody, tocilizumab]. 2007 Jul Interleukin-6 (IL-6) is a multifunctional cytokine that regulates immune response and inflammatory reaction. IL-6 has been shown to play pathological roles in the autoimmune reaction, inflammation, and joint destruction in rheumatoid arthritis, and, therefore, an agent blocking IL-6 actions can be a therapeutics of the disease. Tocilizumab is a humanized anti-human IL-6 receptor antibody designed using genetic engineering technology and the first therapeutic monoclonal antibody developed in Japan. Tocilizumab specifically blocks IL-6 actions and ameliorates the diseases with IL-6 overproduction. It has been clinically developed for rheumatoid arthritis and shown to be effective not only for improving signs and symptoms but also for preventing joint destruction of the disease. In this chapter, immunopharmacology and clinical utility of tocilizumab in rheumatoid arthritis is addressed.
17530672 Arthritis symptoms, the work environment, and the future: measuring perceived job strain a 2007 Jun 15 OBJECTIVE: To develop a measure of job strain related to differing aspects of working with arthritis and to examine the demographic, illness, work context, and psychosocial variables associated with it. METHODS: Study participants were 292 employed individuals with osteoarthritis or inflammatory arthritis. Participants were from wave 3 of a 4-wave longitudinal study examining coping and adaptation efforts used to remain employed. Participants completed an interview-administered structured questionnaire, including a Chronic Illness Job Strain Scale (CIJSS) and questions on demographic (e.g., age, sex), illness and disability (e.g., disease type, pain, activity limitations), work context (e.g., job type, job control), and psychosocial variables (e.g., arthritis-work spillover, coworker/managerial support, job perceptions). Principal component analysis and multiple linear regression were used to analyze the data. RESULTS: A single factor solution emerged for the CIJSS. The scale had an internal reliability of 0.95. Greater job strain was reported for future uncertainty, balancing multiple roles, and difficulties accepting the disease than for current workplace conditions. Participants with inflammatory arthritis, more frequent severe pain, greater workplace activity limitations, fewer hours of work, less coworker support, and greater arthritis-work spillover reported greater job strain. CONCLUSION: The findings underscore the diverse areas that contribute to perceptions of job strain and suggest that existing models of job strain do not adequately capture the stress experienced by individuals working with chronic illnesses or the factors associated with job strain. Measures similar to the CIJSS can enhance the tools researchers and clinicians have available to examine the impact of arthritis in individuals' lives.
16541481 Etanercept treatment in adults with established rheumatoid arthritis: 7 years of clinical 2006 May OBJECTIVE: To evaluate safety and efficacy of longterm etanercept treatment in patients with disease modifying antirheumatic drug (DMARD) refractory rheumatoid arthritis (RA). METHODS: Safety results are reported for 714 patients who received etanercept in one of 7 initial trials or a longterm extension. Efficacy results are reported for 581 patients who enrolled in the extension. RESULTS: Of the 714 patients enrolled in the initial trials, 581 (81%) enrolled in the extension, and 388 (54%) patients are continuing to receive etanercept therapy. The longest individual treatment was 8.2 years, with 3139 total patient-years of etanercept exposure. Rates of serious adverse events (overall rate=14.8 events/100 patient-yrs), serious infections (overall rate=4.2 events/100 patient-yrs), cancer (overall rate=1.0 events/100 patient-yrs), and deaths (overall rate=0.7 events/100 patient-yrs) were stable each year, through 8 years of etanercept exposure. For 356 patients who completed 6 years of etanercept treatment, response rates were ACR20=73%, ACR50=52%, ACR70=27%, DAS28 CRP good response=52%, and DAS28 CRP remission=37% of patients. Similar responses occurred in 167 patients who completed Year 7. Doses of concomitant methotrexate or corticosteroids were reduced in many patients who maintained clinical responses. CONCLUSION: The safety profile of etanercept was consistent over time, with rates of adverse events similar to those reported for patients with RA in general. Durable clinical responses were observed in some patients for 7 years or more. The benefit-to-risk ratio for longterm etanercept treatment remains highly favorable.
18311039 The gene delivery system for rheumatoid synovium. 2008 Feb A gene therapy of synovial tissue is potentially a novel therapeutic method in rheumatoid arthritis (RA). The method induces expression of anti-arthritic molecules in target cells, and is also useful for the investigation of novel therapeutic targets in vitro. Previous studies showed that viral vectors, which can infect non-proliferative cells well, i.e. adenovirus-based vector, were effective in gene transfer to synovial tissue. In this review, we discuss the properties and effectiveness of these methods and our investigations in forcing expression in synovial tissue or cells. The methods of gene transfer are classified into two categories : virus vectors and virus-free vectors. The virus vectors seem to be more applicable to clinical approaches since clinical trials of adeno-associated virus mediated gene therapy were performed in 2007. At the same time, many effective novel virus-free vectors have been developed. Although these gene transfer technologies still have to be improved more to warrant their safety, the gene therapy is an ideal technique in performing "Bench to Clinic and Clinic to Bench" research studies. We hope that it will be applied to RA therapy in near future.
18369528 Clinical strategies for amyloid A amyloidosis secondary to rheumatoid arthritis. 2008 Secondary amyloid A (AA) amyloidosis is an important complication of rheumatoid arthritis (RA) and has remarkable variation in frequency worldwide. It is a serious, potentially life-threatening disorder caused by deposition in organs of AA fibrils, which are derived from the circulatory, acute-phase-reactant, serum amyloid A protein (SAA). The SAA1.3 allele can serve not only as a risk factor for the association of AA amyloidosis but also as a poor prognostic factor in Japanese RA patients. Both the association of AA amyloidosis arising early in RA disease course and symptomatic variety and severity were found in amyloidotic patients carrying the SAA1.3 allele. Etanercept for patients with AA amyloidosis who carry the SAA1.3 allele showed the amelioration of rheumatoid inflammation, including marked reduction of SAA and improvement of renal function. In light of the SAA1.3 allele significance in Japanese RA patients, both a tight control by disease-modifying antirheumatic drugs and an early intervention of biologics for RA inflammation should be applied to suppress acute-phase response, thus preventing the association of AA amyloidosis. It is suggested that SAA plays not only an important role in the development of AA amyloidosis but also interacts with events closely involved in metabolic syndrome as a high- and low-grade inflammatory modulator, respectively.
18718987 Does low-field dedicated extremity MRI (E-MRI) reliably detect bone erosions in rheumatoid 2009 Aug OBJECTIVES: To compare the ability of two different E-MRI units and conventional radiography (CR) to identify bone erosions in rheumatoid arthritis (RA) metacarpophalangeal (MCP) and wrist joints with CT scanning as the standard reference method. METHODS: 20 patients with RA and 5 controls underwent CR, CT and two E-MRI examinations (Esaote Biomedica Artoscan and MagneVu MV1000) of one hand during a 2-week period. In all modalities, each bone of the wrist and MCP joints was blindly evaluated for erosions. MagneVu images were also assessed for the proportion of each bone being visualised. RESULTS: 550 bones were examined. CT, Artoscan, MagneVu and CR detected 188, 116, 55 and 45 bones with erosions, respectively. The majority were located in the carpal bones. The sensitivity of the Artoscan for detecting erosions was higher than that of the MagneVu and CR (MCP joints: 0.68, 0.54 and 0.57, respectively; wrists: 0.50, 0.23 and 0.29). Corresponding specificities for detecting erosions were 0.94, 0.93 and 0.99, respectively, in the MCP joints and 0.92, 0.98 and 0.98 in the wrist. The MagneVu allowed visualisation of 1.5 cm of the ventral-dorsal diameter of the bone. In the wrist, 31.6% of bones were visualised entirely and 37.9% of bones were 67-99% visualised. In MCP joints, 84.2% of bones were visualised entirely and 15.8% of bones were 67-99% visualised. CONCLUSION: With CT as the reference method for detecting erosions in RA hands, the Artoscan showed higher sensitivity than the MagneVu and CR. All imaging modalities had high specificities. The better performance of the Artoscan should be considered when selecting an imaging method in RA.
16924454 [Talonavicular arthrodesis for the rheumatoid foot]. 2006 Nov BACKGROUND: Talonavicular joint fusion has been successfully applied for the surgical treatment of the rheumatoid foot. Several fixation techniques have been suggested for this purpose, however, with high rates of non-union. METHODS: Based on seven cases operated in our division, talonavicular joint fusion with two 3.5 mm compression screws and autologous bone grafting is discussed. Pain in the operated foot under weight-bearing conditions was assessed before surgery and after a mean follow-up of 35 months (range 3-58 months). RESULTS: Solid talonavicular fusion was achieved clinically and radiologically in all patients after 12 weeks. The surgery-related morbidity was low. At follow-up, weight-bearing pain was diminished compared to the preoperative status. CONCLUSIONS: Compression screw arthrodesis of the talonavicular joint in combination with autologous bone grafting is highly successful in rheumatoid arthritis patients.
16504991 Down regulation of multidrug resistance protein-1 expression in patients with early rheuma 2006 Oct BACKGROUND: Methotrexate (MTX) is the current gold standard conventional disease-modifying antirheumatic drug (DMARD) and is effluxed from cells by several transmembrane proteins, including multidrug resistance protein-1 (MRP1). It is hypothesised that the overexpression of these proteins may mediate reduced efficacy of MTX. To date, it is unclear how expression of these proteins changes over time or after exposure to drugs. AIMS: To compare MRP1 expression in newly diagnosed patients with DMARD-naive rheumatoid arthritis with that in healthy controls and to investigate how MRP1 expression changed after exposure to MTX. METHODS: 18 newly diagnosed patients with DMARD-naive rheumatoid arthritis and 14 healthy controls were recruited. Peripheral blood mononuclear cell counts were taken at baseline and after 6 months' treatment with MTX. Cells were separated by density gradient centrifugation and MRP1 expression was measured using the QCRL-1 monoclonal antibody. RESULTS: MRP1 expression in patients did not seem to be up regulated compared with that in healthy controls. In patients who were positive for MRP1 at baseline (61%), treatment with MTX and folic acid led to a marked down regulation of MRP1 expression at 6 months. CONCLUSION: In patients with rheumatoid arthritis expressing MRP1, treatment with MTX and folic acid led to down regulation of MRP1 expression. Further studies are required to determine the mechanism behind this observation and whether MRP1 expression mediates altered efficacy to MTX.
17612988 Upper limb sensorimotor function and functional performance in patients with rheumatoid ar 2007 Jul 15 PURPOSE: Although sensorimotor deficits have been identified in isolated upper limb joints of patients with rheumatoid arthritis (RA), relatively little is known about the presence or consequences of sensorimotor deficits in the upper limb as a whole. To address this, we compared sensorimotor and functional performance in multiple upper limb joints of patients with RA and healthy subjects. METHODS: Global upper limb strength, proprioception (joint position sense) and the time taken to perform 2 common functional daily activities (dressing and eating) were estimated in 31 RA patients and 18 healthy subjects. Disability, pain and clinical disease activity were also assessed in the RA patients. RESULTS: The RA patients were weaker (mean difference 280N, 95% Confidence Interval 172 to 389; P < 0.001), had poorer functional performance (6 sec, CI 8.1 - 23.9; P < 0.001), hand grip strength (117 mmHg, CI 61 - 173; P < 0.001) and proprioceptive acuity (2 degrees , CI 0.4 - 3.5; P < 0.05) than the healthy subjects. Upper limb functional performance and disability in the RA patients were inversely associated with global upper limb (r = -0.54 to -0.36) and hand grip strength (r = -0.51 to -0.32) but not proprioception (r = 0.55 - 0.11). CONCLUSIONS: Compared to healthy subjects, patients with RA had global upper limb sensorimotor deficits. Weakness contributes to poor upper limb function and disability in patients with RA, although the clinical importance of proprioception is unclear.
17541498 Soluble receptor activator of NFkappa B-ligand and osteoprotegerin in rheumatoid arthritis 2007 Dec The aim of our study was to investigate determinants of bone mineral density (BMD) measured by dual X-ray absorptiometry at the lumbar spine (BMD-LS) and at the femoral neck (BMD-FN) in patients with rheumatoid arthritis (RA) with special respect to bone resorbing proinflammatory cytokines and their physiological antagonists. In 142 RA patients the following parameters were measured in parallel with BMD: serum levels of soluble receptor activator of nuclear factor kappa-B-ligand (sRANKL), osteoprotegerin (OPG), interleukin (IL)-6, soluble glycoprotein 130 (sgp130), 25-hydroxyvitamin D3 (25OHD(3)), 1,25-dihydroxyvitamin D3 (1,25[OH](2)D(3)), intact parathyroid hormone, osteocalcin, ionized calcium, renal excretion of pyridinolin and deoxypyridinolin, C-reactive protein, and erythrocyte sedimentation rate (ESR). No significant differences of sRANKL, OPG, IL-6, and spg130 were found between patients with osteoporosis (47.9% of patients), osteopenia (36.6%), and normal BMD (15.5%). However, total sRANKL was significantly higher in postmenopausal women with osteoporosis at FN than in those without (p < 0.05) and showed a negative correlation with BMD-LS in patients older than 60 years (p = 0.01). BMD-LS and BMD-FN (p < 0.001) and total sRANKL (p < 0.01) were negatively related with the age of the patients. Only IL-6 (positive correlation, p < 0.001) and 1,25(OH)(2)D(3) (negative correlation, p < 0.001) but not sRANKL, OPG, and sgp130 were related to disease activity. Using multiple linear regression analysis, menopause was identified as the crucial negative determinant of BMD-LS (R (2) = 0.94, p = 0.001), whereas cumulative glucocorticoid dose (beta = -0.80, p = 0.001) and ESR (beta = -0.44, p = 0.016) were the negative determinants of BMD-FN (R (2) = 0.86, p = 0.001). The results indicate that influences of age and gender must be considered in investigations on the relationship between BMD and sRANKL in RA and that high serum levels of sRANKL seems to be associated with osteoporosis only in subgroups of RA patients.