Browse

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

ID PMID Title PublicationDate abstract
17629902 A longitudinal evaluation of the Center for Epidemiologic Studies-Depression scale (CES-D) 2007 Jul 13 BACKGROUND: The aim of this study was to test the internal validity of the total Center for Epidemiologic Studies-Depression (CES-D) scale using Rasch analysis in a rheumatoid arthritis (RA) population. METHODS: CES-D was administered to 157 patients with RA over three time points within a 12 month period. Rasch analysis was applied using RUMM2020 software to assess the overall fit of the model, the response scale used, individual item fit, differential item functioning (DIF) and person separation. RESULTS: Pooled data across three time points was shown to fit the Rasch model with removal of seven items from the original 20-item CES-D scale. It was necessary to rescore the response format from four to three categories in order to improve the scale's fit. Two items demonstrated some DIF for age and gender but were retained within the 13-item CES-D scale. A new cut point for depression score of 9 was found to correspond to the original cut point score of 16 in the full CES-D scale. CONCLUSION: This Rasch analysis of the CES-D in a longstanding RA cohort resulted in the construction of a modified 13-item scale with good internal validity. Further validation of the modified scale is recommended particularly in relation to the new cut point for depression.
17564786 Methotrexate pneumonia lacking dyspnea and radiographic interstitial patterns during treat 2007 Methotrexate (MTX) pneumonia is an unpredictable and sometimes life-threatening adverse effect occurring in the treatment of rheumatoid arthritis (RA). We present a case of MTX pneumonia lacking severe respiratory symptoms and typical radiographic findings. A 66-year-old man with early RA presented with intermittent fever and nonproductive cough during the MTX therapy, but neither hypoxemia nor dyspnea was a complaint. His chest X-ray films revealed multiple bilateral consolidations, but interstitial infiltrates were not observed. High-resolution computed tomography showed no ground-glass opacities. In contrast, the histological findings of transbronchial lung biopsy (TBLB) samples were characterized by the interstitial infiltration of mononuclear cells and hyperplasia of type II alveolar cells, which are the main features of drug-induced interstitial inflammation. Special stains for microorganisms were negative for the TBLB samples. Although cultures of bronchoalveolar lavage (BAL) fluids were slightly positive for Haemophilus influenzae, intensive antibiotic therapy was ineffective. A discontinuation of MTX followed by steroid therapy induced the patient's dramatic recovery. A new treatment with tacrolimus was started for RA. We would like to emphasize that the histological examinations and microbiological studies using BAL and TBLB are useful for the exclusion of other causes and the diagnosis of MTX pneumonia, especially in a case without typical respiratory symptoms and radiographic patterns.
16982199 Anti-inflammatory cytokines in gingival crevicular fluid in patients with periodontitis an 2006 Aug Cytokines which are produced by host cells play an important role in pathogenesis both rheumatoid arthritis (RA) and chronic periodontitis (CP). In this study, we aim to investigate the levels of Interleukin (IL)-4 and IL-10 in gingival crevicular fluid (GCF). Seventeen patients with CP, 17 patients with RA and 17 healthy controls (HC) were included. The RA group was divided into two groups according to gingival sulcus depths (RA-a: PD < or =3mm, (n=12), RA-b: PD>3mm, (n=5)). For each patient, clinical parameters were recorded. The GCF samples were evaluated by enzyme-linked immunosorbent assay (ELISA) for IL-4 and IL-10 levels. IL-4 levels in the RA-a, RA-b and CP subjects were significantly lower compared to the HC subjects (p<0.05). The mean level of IL-4 in RA-b group was significantly higher than that in CP group (p<0.05). IL-10 mean level in the HC group was higher than those in the other groups (p<0.05). In the RA-a group, higher IL-10 level was found compared to the CP patients (p<0.05). Within the limitations of this preliminary report, it can be concluded that the initiation and progression of periodontal inflammation may be due to a lack or inappropriate response of the anti-inflammatory cytokines in both CP and RA.
16583405 Childbearing decisions and family size among women with rheumatoid arthritis. 2006 Apr 15 OBJECTIVE: To estimate childbearing trends relative to age and stage of family development and to report on childbearing decisions among women with rheumatoid arthritis (RA). METHODS: Information about childbearing history and decisions was collected through structured telephone interviews with an existing cohort of married women with RA (n = 411), and was examined according to women's age at RA diagnosis and when RA was diagnosed relative to when children were born. RESULTS: Almost all women (91.2%) reported at least 1 pregnancy; the majority (85.4%) reported at least 1 live birth. The odds of any pregnancy or a live birth were not significantly different according to age at diagnosis; however, women diagnosed at age < or =18 had fewer pregnancies and fewer children. Similarly, women diagnosed with RA prior to the birth of their first child had the fewest pregnancies and children. Few women (8%) reported being advised to limit family size, although approximately 20% reported that RA had affected their childbearing decisions. Being advised to limit family size was associated with fewer pregnancies and fewer children (P < 0.0001). Consideration of RA in childbearing decisions was more common among women diagnosed with RA at an early age. Women who reported that RA affected childbearing decisions were not less likely to have any pregnancy or any children, but had significantly fewer pregnancies and children. CONCLUSION: Lower birth rates among women with RA may at least in part reflect choices by women to limit family sizes. Future research into the link between RA and fertility should take women's childbearing choices into account.
16451202 Levels of the soluble forms of CD80, CD86, and CD83 are elevated in the synovial fluid of 2006 Jan The release of soluble forms of CD80 (sCD80), CD86 (sCD86), and CD83 (sCD83) provide a potentially powerful immunoregulatory mechanism. We therefore investigated the potential presence and relative levels of these molecules in the synovial fluid (SF) and serum of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Serum and SF levels were measured by enzyme-linked immunosorbent assay. Serum levels of sCD80, sCD86, and sCD83 in RA and OA patients were similar to those present in normal donor serum (NDS) and the SF of OA patients. In contrast, when compared with NDS and OA SF levels, almost all RA SF samples had elevated sCD83 levels (32/35, >0.63 ng/ml) and a substantial proportion had elevated sCD80 (13/29, >0.22 ng/ml) or sCD86 (16/33, >2.31 ng/ml) levels. Analysis of matched pairs of serum and SF from RA patients demonstrated that the SF/serum ratio for sCD80 (95% CI = 1.7-3), sCD86 (95% CI = 1.5-3.1), and sCD83 (95% CI = 3.6-7.8) levels was >1 in almost all patients. In conclusion, this study shows that the SF from almost all RA patients contain elevated levels of sCD83 and the majority of these samples also contain elevated levels of sCD80 and/or sCD86. These molecules may play a role in modulating immune responses within the rheumatoid joint.
16400533 Contribution of partner support in self-management of rheumatoid arthritis patients. An ap 2006 Feb The aim of this exploratory study was to test the applicability of a model derived from the Theory of Planned Behavior on self-management. In this model social support from the partner, attitude and self-efficacy are determinants of intention, and intention and self-efficacy are determinants of self-management. We tested the model on rheumatoid arthritis patients who have a partner, using regression analyses and structural equation models. Partner support and attitude partly explained the variance in intention. Intention in turn partly explained the variance in self-management. Self-efficacy showed a tendency to positively affect intention and self-management. The present study provided moderate support for the use of the constructs and ideas derived from the Theory of Planned Behavior-attitude, social support, self-efficacy, and intention-in predicting and explaining self-management.
17389855 [Infliximab-induced skin reaction with visceral manifestations and high levels of anti-DNA 2007 Mar BACKGROUND: Infliximab is a monoclonal anti-Tumor Necrosis Factor alpha-antibody (anti-TNFalpha) that has demonstrated its efficacy in the treatment of rheumatoid arthritis, Crohn's disease and psoriasis. CASE REPORT: We report the case of a 59 year-old woman with a 20-year history of rheumatoid arthritis consulting for an atypical erythematosus rash 18 months after her first infusion of infliximab. The rash was associated with inflammatory syndrome, incipient renal failure and high levels of antinuclear antibodies with the presence of anti-dsDNA antibodies. Lack of specificity in both skin manifestations and histology ruled out a diagnosis of drug-induced lupus. Discontinuation of treatment with infliximab resulted in improvement of all clinical signs together with a significant decrease of antinuclear antibody titers within six months. DISCUSSION: Induction of antinuclear antibodies and/or anti-dsDNA antibodies is often seen in patients treated with TNFalpha inhibitors. Cases of true systemic lupus erythematosus or anti-TNFalpha-related eruption in a context of autoimmunity, as seen in our patient, have been reported only rarely. All cases were reversible upon discontinuation of treatment.
17039318 Hypersensitivity reaction against influenza vaccine in a patient with rheumatoid arthritis 2006 A 58-year-old Japanese woman with rheumatoid arthritis (RA) suffered from high fever triggered by administration of an influenza vaccine after a 4-month-long effective treatment course with the TNF-alpha inhibitor etanercept. Influenza vaccine had been previously administrated safely to the patient before initiation of etanercept therapy. The fever occurred without other symptoms soon after vaccine administration, progressed to high fever 1 day later, and spontaneously resolved the second day. The clinical course appears to be compatible with drug fever closely associated with immediate hypersensitivity (in particular, late-phase type I allergic reaction), in which T helper (Th) 2 cells play a crucial role. Etanercept can strongly suppress Th1-mediated reactions; therefore, Th2 activity may be augmented by etanercept treatment in aspect of antagonism between Th1 and Th2 mechanisms. In RA patients who receive treatment with TNF-alpha inhibitor such as etanercept, activation of Th2-mediated immune responses such as immediate hypersensitivity may be a necessary side effect for those who receive vaccinations.
17655372 Clinical pharmacokinetics and use of infliximab. 2007 Tumor necrosis factor-alpha (TNFalpha) is a key proinflammatory cytokine involved in chronic inflammatory diseases. Infliximab, a chimeric (human-murine) monoclonal IgG1 anti-TNFalpha antibody, is used in the treatment of Crohn's disease (including fistulising disease) and rheumatoid arthritis (in combination with methotrexate) if standard treatments have failed. The indications for infliximab have recently been expanded to include ankylosing spondylitis, psoriatic arthritis, psoriasis and ulcerative colitis. The biological agent infliximab is given by multiple intravenous infusions in a dosage of 3-5 mg/kg (initially at weeks 0, 2 and 6; subsequently in intervals of 4-8 weeks). In controlled trials, clinical response rates of 20-40% have been achieved with such regimens in Crohn's disease and rheumatoid arthritis. However, the therapeutic benefits must be balanced against the risks of a variety of severe adverse events (e.g. severe infections including tuberculosis, hepatotoxicity, infusion reactions, serum sickness-like disease and lymphoma). Following single and multiple infusions of infliximab, no relevant differences in median concentration-time profiles have been observed between patients with Crohn's disease, patients with rheumatoid arthritis and patients with psoriasis. The apparent volume of distribution of the high-molecular-weight infliximab (149.1 kDa) is low (3-6L) and represents the intravascular space. The long persistence in this compartment (elimination half-life 7-12 days, mean residence time 12-17 days) is due to the very low systemic clearance of about 11-15 mL/hour (0.18-0.25 mL/minute). Elimination of infliximab is most probably accomplished through degradation by unspecific proteases. During multiple infusions (every 4-8 weeks), no accumulation was observed, and serum concentrations and the area under the plasma concentration-time curve of infliximab increased in proportion to the infused dose, indicating linear pharmacokinetics. Co-medication with methotrexate delayed the decline in the serum concentrations of infliximab. When relating serum concentrations to the clinical response in patients with rheumatoid arthritis and patients with Crohn's disease, it can be assumed that trough concentrations above 1 microg/mL could be used as a kind of therapeutic target. In the future, identification of biomarkers for (non-)response and risk factors for adverse drug reactions would be very helpful. Furthermore, combined biological, pharmacokinetic, pharmacogenomic and clinical studies have not yet been performed and are needed to optimise the therapeutic potential of infliximab, which is currently established as a rescue treatment in refractory patients.
18489499 Bayesian meta-analysis of multiple treatment comparisons: an introduction to mixed treatme 2008 Sep Recently, mixed treatment comparisons (MTC) have been presented as an extension of traditional meta-analysis by including multiple different pairwise comparisons across a range of different interventions. MTC allow for indirect comparisons and can therefore provide very useful information for clinical and reimbursement decision-making in the absence of head-to-head data. In this article, we provide an introductory overview of MTC illustrated with example analyses of different drug treatments in rheumatoid arthritis using a continuous patient-reported end point. As a background, we start with an overview of the traditional meta-analyses for pairwise trials, and the difference between a traditional approach and a Bayesian approach. Next, the Bayesian MTC for continuous outcomes are presented. We finish with a discussion of how MTC can best be presented in order to maximize acceptance by target audiences, i.e., clinicians and market access decision-makers.
17885866 Assessing the consistency of traditional Chinese medicine with multiple correlative active 2007 The problem of controlling the quality of raw materials and/or final product of traditional Chinese medicine (TCM) has been studied. Earlier proposed consistency index to assess the consistency of quality of raw materials and/or final product processed or manufactured from different locations or sites has only focused on a single (i.e., the most active) component assuming that the most active component can be quantitatively identified among multiple active components. In this paper, we extend such results to the case of two correlative components. Sampling plans (sample sizes) are obtained for various combinations of study parameters. An example concerning a TCM for treating patients with rheumatoid arthritis is presented to illustrate the use of the proposed method. Some concluding remarks are also provided.
17302909 Effect of interleukin-4 on vascular endothelial growth factor production in rheumatoid syn 2007 Mar Interleukin (IL)-4 has been demonstrated to have anti-inflammatory and anti-tumour activity. Because aberrant angiogenesis is a significant pathogenic component of tumour growth and chronic inflammation, we investigated the effect of IL-4 on the production of vascular endothelial growth factor (VEGF) by synovial fibroblasts derived from patients with rheumatoid arthritis (RA). Fibroblast-like synoviocytes (FLS) were prepared from synovial tissues of RA and incubated with different concentrations of IL-4 in the presence or absence of transforming growth factor (TGF)-beta. VEGF level was measured by enzyme-linked immunosorbent assay and semiquantitative reverse transcription--polymerase chain reaction. Treatment of FLS with IL-4 alone caused a dose-dependent increase in VEGF levels. In contrast, IL-4 exhibited the inhibitory effect on VEGF production when FLS were stimulated with TGF-beta. Combined treatment of IL-4 and IL-10 inhibited TGF-beta-induced VEGF production in an additive fashion. TGF-beta increased the induction of cyclooxygenase-2 mRNA, which was inhibited significantly by the treatment of IL-4. NS-398, a COX-2 inhibitor, inhibited TGF-beta-induced VEGF production in a dose-dependent manner. Furthermore, exogenous addition of prostaglandin E2 (PGE2) restored IL-4 inhibition on TGF-beta induced VEGF production. Collectively, our results suggest that IL-4 have an anti-angiogenic effect, especially in the inflammatory milieu of RA by inhibiting the VEGF production in synovial fibroblasts.
17212998 Role of abatacept in the management of rheumatoid arthritis. 2006 Nov BACKGROUND: Rheumatoid arthritis (RA) has been associated with significant morbidity and economic burden. Traditional pharmacotherapy (eg, NSAIDs, corticosteroids, disease-modifying antirheumatic drugs [DMARDs]) can be inadequate in controlling symptoms and disease progression. Abatacept is the first selective co-stimulation modulator approved by the US Food and Drug Administration for the management of RA. It is a fusion protein developed to modulate the T-cell co-stimulatory signal that is mediated through the CD28-CD80/86 pathway. OBJECTIVE: The objective of this manuscript was to review the clinical pharmacology, pharmacokinetic and pharmacodynamic properties, tolerability, and clinical efficacy of abatacept. METHODS: MEDLINE and International Pharmaceutical Abstracts were searched through June and May, respectively, of 2006 using the term abatacept or CTLA4-Ig. All prospective, randomized, Phase II and III trials, and their extension phases, were included. RESULTS: Phase II and III clinical trials found that abatacept, at a dose of 10 mg/kg administered as a short i.v. infusion in combination with DMARDs, was associated with significant clinical benefit in patients with active RA. After 6 months of treatment, the American College of Rheumatology (ACR) criteria for 20% clinical improvement (ACR20 response) was attained in 41.9% to 67.9% of patients who received abatacept compared with 19.5% to 39.7% of patients who received placebo (P < 0.001). The percentages of patients achieving the ACR criteria for 50% and 70% clinical improvement (ACR50 and ACR70) were 20.3% to 39.9% and 10.2% to 19.8%, respectively, in the groups that received abatacept compared with 3.8% to 16.8% and 1.5% to 6.5%, respectively, in the patients who received placebo (P = 0.03 and P < 0.001). Additionally, abatacept was found to improve disease activity, physical function, pain, and health-related quality of life (HRQOL). The most commonly reported adverse effects associated with abatacept treatment were headache (18.2%), upper respiratory tract infection (12.7%), nasopharyngitis (11.5%), and nausea (11.5%). The incidences of infections and serious infections were higher in the group that received abatacept compared with patients who received placebo (53.8% vs 48.3% and 3.0% vs 1.9%, respectively; P not reported). No significant between-group differences in mortality were found. CONCLUSIONS: Available evidence suggests that abatacept was effective in controlling symptoms and improving HRQOL in patients with active RA and an inadequate response to DMARD therapy. The most commonly reported adverse effects associated with abatacept treatment were headache, upper respiratory infection, nausea, and nasopharyngitis. Additional trials are needed to determine the long-term safety profile of this agent and whether the clinical benefits of abatacept found in the current clinical trials will be sustained over time.
18309254 [A comparative evaluation of the diagnostic value of anti-cyclic citrullinated peptide and 2008 Feb BACKGROUND: Despite its unsatisfactory specificity, rheumatoid factor (RF) is the only serologic marker included in the diagnostic criteria of the American College of Rheumatology (ACR) for rheumatoid arthritis. Recently, the diagnostic value of anti-cyclic citrullinated peptide (CCP) antibodies has been emphasized in rheumatoid arthritis (RA) due to its high specificity. To evaluate the second generation of anti-CCP antibodies as a diagnostic marker, we evaluated anti-CCP test in 163 individuals. METHODS: The study population was divided into the following four groups: RA group (n=18), other disease group with arthritic symptoms (n=44), other disease group without arthritic symptoms (n=45), and healthy group (n=56). Anti-CCP was measured by an ELISA analyzer (Coda, Bio-Rad, USA) with Immunoscan RA (Euro-Diagnostica, Malmo, Sweden) and RF was measured by an automated chemistry analyzer (Toshiba, Japan) with RF-LATEX X1 (Denka Seiken, Japan). RESULTS: The sensitivity of anti-CCP and RF was 72.2% and 100%, respectively, and the respective figures for the specificity were 96.6% and 73%. On each ROC curve, the area under the curve was 0.867 for anti-CCP and 0.959 for RF. In other disease groups, most of the false positive cases of RF were found in the patients with hyperlipidemia or HBV carriage. However, anti-CCP was not detected in any of the patients with these two conditions. False positive rates of RF in the three control groups were 34.1% in other disease group with arthritic symptoms, 48.9% in the other disease group without arthritic symptoms, and 3.6% in healthy group. The respective figures for anti-CCP were 6.8%, 2.2%, and 1.8%. CONCLUSIONS: The specificity of anti-CCP antibodies was higher than that of RF for discriminating RA from other diseases, especially in the patients with hyperlipidemia or HBV carriage. With its high specificity, anti-CCP antibodies can play an additive role in establishing the diagnosis of RA in patients with RF positivity.
18792823 Interleukin 7-induced lymphoid neogenesis in arthritis: recapitulation of a fetal developm 2008 Sep 6 Chronic inflammatory diseases such as rheumatoid arthritis (RA) are associated with the de novo formation of organised lymphoid tissue in a subpopulation of patients. The aberrant expression of cytokines and chemokines by stromal cells plays an important role in recruitment and survival of effector cells of the immune system and the development of ectopic tertiary lymphoid organs (TLOs). TLOs may promote the persistence of inflammation and the recognition of self antigens. Recent studies in man and mice now indicate that interleukin 7 (IL-7) is implicated in the formation of TLOs and progression of chronic inflammation.
19210653 Obstructive bronchiolar disease identified by CT in the non-transplant population: analysi 2009 Apr BACKGROUND AND OBJECTIVE: Obstructive bronchiolar disease or constrictive bronchiolitis, particularly in non-transplant patients, is poorly understood. This study identified the associated diseases, presenting features, and clinical course of obstructive bronchiolar disease identified by CT in the non-transplant adult population. METHODS: Retrospective single-centre study of 29 consecutive patients clinically diagnosed to have an obstructive bronchiolar disease based on the presence of respiratory symptoms and abnormal CT findings consisting of mosaic perfusion pattern with air trapping. RESULTS: The median age was 54 years (range, 25-80 years); 20 were women (69%) and four patients (14%) had a smoking history. All 29 patients presented with respiratory symptoms, predominantly dyspnoea. The most common cause of obstructive bronchiolar disease was rheumatoid arthritis (34%). Other causes included hypersensitivity pneumonitis, multiple carcinoid tumorlets, Sjögren's syndrome, paraneoplastic pemphigus, inflammatory bowel disease and Swyer-James syndrome. The underlying cause was not identifiable in nine patients (31%), that is, cryptogenic constrictive bronchiolitis. An obstructive pattern was seen on pulmonary function testing in most patients (86%) with the exception of those with hypersensitivity pneumonitis and extreme obesity. Management usually included corticosteroid therapy, inhaled and oral, and bronchodilator therapy. Additional medications included macrolides, cytotoxic agents and other immunomodulator therapy. Pharmacologic therapy did not provide improvement in pulmonary function in the majority of patients but the follow-up data were limited. CONCLUSIONS: Diverse causes and underlying diseases are associated with obstructive bronchiolar disease diagnosed radiologically in the non-transplant adult population. Rheumatoid arthritis-associated and cryptogenic constrictive bronchiolitis are found in over one-half of these patients. Most patients with obstructive bronchiolar disease do not appear to improve with currently available therapy.
18276737 Caspase-8 has an essential role in resveratrol-induced apoptosis of rheumatoid fibroblast- 2008 Mar OBJECTIVE: Resveratrol is a naturally occurring polyphenol, which possesses chemotherapeutic potential through its ability to trigger apoptosis. The objective of this study was to investigate the major determinant for the apoptotic cell death induction by resveratrol in fibroblast-like synoviocytes (FLS) derived from patients with RA. METHODS: The effect of resveratrol on apoptotic cell death was quantified in a population of subG1 in RA FLS by flow cytometry. The underlying signalling mechanism for apoptotic death was examined by analysing mitochondrial membrane potential, activation of the caspase cascade and translocation of Bid. RESULTS: We show that activation of caspase-8 is essential for triggering resveratrol-induced apoptotic signalling via the involvement of the mitochondrial pathway in RA FLS. Our findings also suggest that this enhanced apoptosis caused by resveratrol occurred in RA FLS irrespective of p53 status. Exposure to resveratrol caused extensive apoptotic cell death, along with a caspase-dependent (activation of caspase-9 and -3, poly ADPribose polymerase (PARP) cleavage and mitochondrial cytochrome c release) or caspase-independent [translocation of apoptosis-inducing factor (AIF) to the nucleus] signalling pathway. Analysis of upstream signalling events affected by resveratrol revealed that the activated caspase-8 triggered mitochondrial apoptotic events by inducing Bid cleavage without any alteration in the levels of Bax, Bcl-xL or Bcl2. The caspase-8 inhibitor or over-expression of crmA abrogated cell death induced by resveratrol and prevented processing of the downstream cascade. CONCLUSION: The results suggest that resveratrol causes activation of caspase-8, which in turn results in modulation of mitochondrial apoptotic machinery to promote apoptosis of RA FLS.
18310134 Involvement of TWEAK/Fn14 interaction in the synovial inflammation of RA. 2008 Apr OBJECTIVE: TWEAK, TNF-like weak inducer of apoptosis, induces not only apoptosis of some tumour cells, but also proliferation of endothelial cells, and angiogenesis. It is known that TWEAK induces production of cytokines that are involved in the pathogenesis of RA. However, it is not clear how TWEAK takes part in the synovitis of RA. In this study, we investigated the role of TWEAK/fibroblast growth factor-inducible 14 (Fn14) interaction in the synovitis of RA. METHODS: TWEAK and Fn14 expression on RA and OA synovial cells (SCs) were analysed by FACS. Synovial fibroblasts (SFs) or freshly isolated SCs were cultured in the presence or absence of recombinant TWEAK (rTWEAK) and anti-TWEAK or anti-Fn14 mAbs. Cell proliferation, cytokine/chemokine production and intercellular adhesion molecule (ICAM-1) expression were measured by WST-8 [2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2, 4-disulfophenyl)-2H-tetrazolium monosodium salt], ELISA and FACS, respectively. RESULTS: TWEAK expression was detected on CD45-positive population in RA synovium, whereas Fn14 was detected on both CD45-positive and CD45-negative populations. Cultured RA and OA SFs showed higher proliferation and produced IL-6, IL-8 and MCP-1 in response to rTWEAK. Cell proliferation and cytokine production of freshly isolated SCs from RA patients were suppressed by anti-TWEAK and anti-Fn14 mAbs. ICAM-1 expression on RA, but not OA, SFs was up-regulated by rTWEAK. CONCLUSIONS: These data suggest that TWEAK/Fn14 interaction plays a substantial role in the synovitis of RA, by directly inducing the proliferation of SFs, and by up-regulating the production of inflammatory cytokines/chemokines as well as the expression of ICAM-1.
16460970 Falls risk is associated with pain and dysfunction but not radiographic osteoarthritis in 2006 Jun OBJECTIVE: To describe the association between knee and hip radiographic osteoarthritis (ROA), a measure of knee pain, stiffness and functional ability and objectively measured physiological falls risk predictors. METHODS: Cross-sectional, population-based study of 850 randomly selected men and women aged 50-80 years (mean 62.5, SD 7.4). Falls risk (Z score) was determined objectively with the short form Physiological Profile Assessment (PPA). Two observers assessed knee and hip ROA using the Altman atlas. Pain, stiffness and functional ability were assessed using the Western Ontario McMasters Osteoarthritis index (WOMAC). RESULTS: Overall, the study population was at a mild risk of falling. In multivariable analysis, the WOMAC function and pain score were significantly associated with reaction time, balance, proprioception, knee extension strength, and edge contrast sensitivity. Stiffness was associated with knee extension strength and edge contrast sensitivity. Males had a dose response association between the global WOMAC score and falls risk (r=0.17, P<0.001). Those who reported a global WOMAC score of 50 and above had a higher risk of falling compared to those with a score below 50 (Z score: 0.53 vs 0.14, P<0.001). Hip joint space narrowing (JSN) was significantly associated with knee extension strength (r=-0.10, P=0.003), however, no other significant associations were observed between ROA and falls risk predictors. CONCLUSION: Self-reported functional ability and pain, and to a lesser extent, stiffness (but not knee and hip ROA), have a modest but independent association with physiological predictors of falls risk.
17998077 A simple sample size formula for analysis of covariance in randomized clinical trials. 2007 Dec OBJECTIVE: Randomized clinical trials that compare two treatments on a continuous outcome can be analyzed using analysis of covariance (ANCOVA) or a t-test approach. We present a method for the sample size calculation when ANCOVA is used. STUDY DESIGN AND SETTING: We derived an approximate sample size formula. Simulations were used to verify the accuracy of the formula and to improve the approximation for small trials. The sample size calculations are illustrated in a clinical trial in rheumatoid arthritis. RESULTS: If the correlation between the outcome measured at baseline and at follow-up is rho, ANCOVA comparing groups of (1-rho(2))n subjects has the same power as t-test comparing groups of n subjects. When on the same data, ANCOVA is used instead of t-test, the precision of the treatment estimate is increased, and the length of the confidence interval is reduced by a factor 1-rho(2). CONCLUSION: ANCOVA may considerably reduce the number of patients required for a trial.