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ID PMID Title PublicationDate abstract
19449480 Single measurements of C-reactive protein and disease activity scores are not predictors o 2009 Jan BACKGROUND: Although inflammation has a defined role in the pathogenesis of atherosclerosis, the link between rheumatoid arthritis (RA) parameters of disease activity and atherosclerotic findings are not defined. OBJECTIVE: To investigate the association between subclinical carotid atherosclerosis and clinical/laboratorial parameters of RA systemic inflammatory activity. METHODS: Seventy-one RA patients were consecutively selected and compared to 53 healthy controls. Smoking, diabetes and hypertension were excluded, as well as the use of statins or fibrates. B-mode carotid ultrasound was performed in all subjects. CRP, ESR and fibrinogen were determined in both groups. Clinical assessment of RA activity included DAS 28 and SDAI. Correlation between plaques and intima-media thickness (IMT) of common carotid arteries and inflammatory parameters was evaluated. RESULTS: Carotid plaques were more prevalent in RA patients than in controls (14.1% vs. 1.9 %, p=0.02) and marginally increased IMT was observed (0.72 +/- 0.17 vs. 0.67 +/- 0.15 mm, p=0.07). RA patients with plaques had older age (p=0.001) and increased IMT (p<0.001), but low SDAI (p=0.025) compared to those without plaques. RA patients with plaques had also longer disease duration, although this difference did not reach statistical significance (p=0.06). No significant correlations were found between IMT and ESR (p=0.80), CRP (p=0.75), fibrinogen (p=0.94), HAQ (p=0.89) and DAS 28 (p=0.13). CONCLUSIONS: Carotid atherosclerosis is more frequently detected in RA but its prevalence was not correlated with isolated inflammatory markers measurement or noncumulative activity scores. These findings reinforce the need to evaluate subclinical atherosclerosis in RA patients, and to find predictors of atherosclerotic lesions.
21071478 'If I didn't have RA I wouldn't give them house room': the relationship between RA, footwe 2011 Mar OBJECTIVES: The aim of this study was to develop a greater understanding of the impact of RA on women's self-image and self-presentation via an exploration of their clothing choices. METHODS: Located within a qualitative symbolic interactionist approach, 15 women with RA (age range 38-74 years, disease duration 1-47 years) each participated in two interviews. The first explored the impact of RA on their feelings about their bodies and their appearance; the second explored the factors that informed their clothing choices and the way they presented themselves. All interviews were digitally recorded and transcribed verbatim, digital photographs of the women's clothes and shoes were taken. Data were analysed jointly by both authors using thematic network analysis. RESULTS: Shoes were identified as greatly influencing the women's clothing choices and how they presented themselves. Three themes were identified that explored the structural and symptomatic impact of RA on the women's feet, the strategies they had developed to resolve their footwear needs outside of prescription footwear and the significant impact that footwear had on their clothing choices and self-presentation. Insights from these data highlight the polarity that exists between the clinical, functional attitudes towards shoes and their social status. CONCLUSION: While aesthetic issues challenge the acceptability of prescription footwear, problems also exist with the functionality and comfort of footwear available on high streets. A more collaborative approach to the design of footwear is required for both prescription and mainstream footwear to meet the needs of women with RA.
19950274 Specifically modified osteopontin in rheumatoid arthritis fibroblast-like synoviocytes sup 2009 Dec OBJECTIVE: Osteopontin (OPN) is expressed by fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA), but its pathologic role is still obscure. The present study was undertaken to analyze the role of OPN in RA by focusing on its effects on cell-cell interactions between FLS and B lymphocytes. METHODS: FLS obtained from 10 patients with RA and 10 non-RA subjects and a B lymphocyte cell line were studied. The characteristics of OPN expression by FLS were analyzed by Western blotting, immunoprecipitation, and immunofluorescence studies. In cocultures of FLS and B lymphocytes, the effects of OPN on adhesion of B lymphocytes to FLS and the consequent production of interleukin-6 (IL-6) were analyzed in experiments involving overexpression and knockdown of OPN and inhibitory studies with an OPN-blocking antibody. In vivo, the expression of OPN in RA synovium was examined by immunohistochemistry. RESULTS: A specifically modified 75-kd form of OPN was predominantly expressed in RA FLS, and this was associated with expression of >200-kd thrombin-cleaved OPN that was crosslinked with fibronectin and localized on the surface of the FLS. In FLS-B lymphocyte cocultures, 75-kd OPN-positive FLS produced a significantly higher amount of IL-6 than did 75-kd OPN-negative FLS. When the FLS were separated from B lymphocytes or cultured alone, the production of IL-6 was low and was not significantly different between these 2 culture conditions. Moreover, OPN overexpression enhanced production of IL-6 in 75-kd OPN-positive FLS-B lymphocyte cocultures. Addition of the OPN-blocking antibody inhibited the adhesion of B lymphocytes to FLS. Immunohistochemical analyses revealed that localization of IL-6-positive cells coincided with the sites at which OPN and B lymphocytes were colocalized. CONCLUSION: Specifically modified 75-kd OPN was expressed by RA FLS. This form of OPN affected FLS-B lymphocyte interactions by supporting the adhesion of B lymphocytes to FLS and enhancing the production of IL-6.
18336874 Safety of biologic therapy in rheumatoid arthritis and other autoimmune diseases: focus on 2009 Feb OBJECTIVES: To review the safety of biologic agents used to treat rheumatoid arthritis (RA) and other autoimmune diseases, with a focus on rituximab. METHODS: Information was gathered from a search of the PubMed database and from major congress abstract listings through June 2007. RESULTS: Rituximab is approved for treating RA in patients with an inadequate response to TNF inhibitors and is under study in other indications for RA and other autoimmune disorders. The current safety profile of rituximab in RA is known from Phase II and III studies conducted preapproval, treating approximately 750 patients, as well as from long-term extension studies with repeated therapy. Clinical trials have established that the most common adverse events are infusion-associated reactions, seen in 29 to 40% of patients, most of which are mild to moderate and occur following the first rituximab infusion, with incidence and severity decreasing with subsequent infusions. Rates of infections and serious infections to date are within the range expected for RA patients treated with other biologic agents, but the longer term effects of B-cell depletion and the effects of repeated treatment on the risk of infections are uncertain. Information is limited for rituximab safety in other autoimmune disorders but current data do not suggest that there is a significant difference in adverse events from that previously reported. CONCLUSIONS: Rituximab is an important addition to the rheumatologist's armamentarium for the treatment of difficult RA and ongoing trials will determine its utility in other indications for RA and other autoimmune conditions. The true safety profile of rituximab will emerge as larger numbers of patients are treated in routine clinical practice.
20509716 Belimumab: anti-BLyS monoclonal antibody; Benlysta; BmAb; LymphoStat-B. 2010 Belimumab is a fully human monoclonal antibody for the treatment of autoimmune disorders that is being developed by Human Genome Sciences and GlaxoSmithKline. Two pivotal phase III trials in systemic lupus erythematosus have been concluded with the primary endpoints being met in both studies. A phase II trial in rheumatoid arthritis has also been completed, with positive results. Marketing authorization submissions are being prepared in the major markets worldwide. This review discusses the development history and scientific profile of belimumab.
19686922 Single-stage comprehensive surgical treatment of the rheumatoid arthritis temporomandibula 2009 Sep PURPOSE: To prospectively evaluate the outcomes of single-stage reconstruction of patients with rheumatoid arthritis (RA) with temporomandibular joint (TMJ) pathologic features and an associated dentofacial deformity. PATIENTS AND METHODS: Fifteen patients (12 females, 3 males) with RA underwent TMJ reconstruction, with or without a Le Fort I osteotomy in a single operation. Clinical and radiographic examinations were performed before surgery, immediately after surgery, and at the longest follow-up intervals. Numeric analog scales were used for subjective evaluation of TMJ pain, jaw function, diet, and disability. The maximal interincisal opening, lateral excursions, and TMJ crepitus were recorded at each visit. Standardized cephalometric acetate tracings were superimposed to assess for surgical (immediately after surgery compared with before surgery) and postoperative (longest follow-up interval compared with immediately after surgery) changes. RESULTS: The average patient age was 27.4 years (range 15 to 61), and the follow-up was 34.3 months (range 10 to 77). At the longest follow-up interval, all 15 patients had had a statistically significant reduction in the incidence and severity of TMJ pain and headaches. The average maximal interincisal opening increased after surgery, but the difference was not statistically significant. Lateral excursions decreased significantly after surgery. Dietary restrictions and disability were significantly improved, and TMJ crepitus had reduced significantly. The average advancement at point B was 21.7 mm (range 14 to 28), and the postoperative change at the longest follow-up interval was 0.1 mm (range 0 to 1). The average pogonion advancement was 29.2 mm (range 19.5 to 38), with a postoperative change of 0.2 mm (range 0 to 1). The average gonion vertical lengthening was 20.7 mm (range 10.5 to 29) with a postoperative change of 1.4 mm (range 0 to 4.5). The average occlusal plane angle change was a decrease of 20.7 degrees (range 16 degrees to 26 degrees), with a postoperative change of 0.4 degrees (range 0 degrees to 2 degrees). Of the 15 patients, 10 had undergone maxillary orthognathic surgery performed at the same operation. The average advancement of these 10 patients at point A was 3 mm (range 2 to 7), and the postoperative change was 0.5 mm (range 0 to 1). CONCLUSIONS: Surgical correction of rheumatoid-associated TMJ disease and the resulting dentofacial deformity can successfully be performed in a single operation using custom-made TMJ total joint prostheses to reconstruct the TMJs and advance the mandible, with maxillary orthognathic surgery and genioplasty performed at the same operation when indicated. The significant reduction in TMJ dysfunction symptoms and the long-term stability of the orthognathic surgery movements show the benefits and predictability of treating these complex patients with this treatment protocol.
19581278 Anti-infliximab and anti-adalimumab antibodies in relation to response to adalimumab in in 2010 May OBJECTIVE: To investigate how antibodies against anti-tumour necrosis factor (anti-TNF) agents influence response after switching from infliximab to adalimumab in rheumatoid arthritis (RA). METHODS: This cohort study consisted of 235 patients with RA, all treated with adalimumab. At baseline 52 patients (22%) had been previously treated with infliximab ('switchers'), and 183 (78%) were anti-TNF naive. Disease activity (using the 28-joint count Disease Activity Score (DAS28)) and presence of antibodies against infliximab and adalimumab were assessed. Clinical response to adalimumab was compared between switchers and anti-TNF naive patients and their anti-infliximab and anti-adalimumab antibody status. RESULTS: After 28 weeks of adalimumab treatment the decrease in DAS28 (Delta DAS28) for the 235 patients was 1.6+/-1.5 (mean+/-SD). Anti-adalimumab antibodies were detected in 46 patients (20%). Delta DAS28 was 1.8+/-1.4 in patients without anti-adalimumab and 0.6+/-1.3 in patients with anti-adalimumab (p<0.0001). Thirty-three of the 52 switchers (63%) had anti-infliximab antibodies. Patients with anti-infliximab more often developed anti-adalimumab than anti-TNF naive patients (11 (33%) vs 32 (18%); p=0.039). Delta DAS28 was greater for anti-TNF naive patients (1.7+/-1.5) than for switchers without anti-infliximab antibodies (Delta DAS28=0.9+/-1.4) (p=0.009). Delta DAS28 for switchers with anti-infliximab was 1.2+/-1.3 and did not differ significantly from anti-TNF naive patients (p=0.262). CONCLUSION: Switchers with anti-infliximab antibodies more often develop antibodies against adalimumab than anti-TNF naive patients. Response to adalimumab was limited in switchers without anti-infliximab antibodies, which raises the question whether a second anti-TNF treatment should be offered to patients with RA for whom an initial treatment with an anti-TNF blocker fails, in the absence of anti-biological antibodies.
21071479 Ultrasound Doppler measurements predict success of treatment with anti-TNF-α drug in 2011 Mar OBJECTIVE: To investigate the predictive ability of core outcomes applied in RA trials, including ultrasound (US) Doppler (USD) measurements differentiating patients who remain on anti-TNF-α therapy following 1 year. METHODS: Patients with RA in anti-TNF-α therapy were followed 1 year after therapy initiation. All patients had wrist involvement. At baseline, 2 weeks, 26 weeks and 1 year a USD examination, clinical examination including tender and swollen joint count, visual analogue scale (VAS) global and HAQ, biochemical measures and 28-joint DAS (DAS28) were collected for all patients. The amount of USD signal in the synovium was quantified by measuring the percentage of colour pixels-the colour fraction (CF). Predictive validity for patients who remain on anti-TNF-α therapy after 1 year was assessed for both USD measurements and other disease measures. Baseline values of disease measures of patients who remained on treatment after 1 year was compared with those who stopped therapy. RESULTS: The study cohort consisted of 109 patients. In this study, the baseline CF was the only measure predicting which patients would stay on the initial anti-TNF-α therapy for 1 year, evaluated using the square-root of CF (P = 0.024). The other disease markers could not significantly differentiate between the two groups of patients, with P-values of 0.86 and 0.98 for tender and swollen joint count, respectively, 0.86 for CRP, 0.24 for VAS, 0.10 for HAQ and 0.38 for DAS28. CONCLUSION: There is now evidence to support that baseline USD, in contrast to clinical measures, can predict which patients will remain on anti-TNF-α 1 year after initiating therapy.
19579967 The efficacy of disease modifying anti-rheumatic drugs in rheumatoid arthritis in local pa 2009 Feb 15 The primary objective of the study is to assess the efficacy of the 'Disease Modifying AntiRheumatic Drugs (DMARDs) on the disease activity in Rheumatoid Arthritis (RA) in the local patients of Karachi. The secondary objective is to evaluate whether the combination of two concurrent DMARDs (Combination Therapy) is superior to a single DMARD (Mono-therapy). This is an open labeled retrospective case series. One hundred and five consecutive patients fulfilling 1987 ACR criteria for the diagnosis of RA were initially selected from the case notes of out patients department. Sixty nine patients fulfilled the inclusion criteria and were finally recruited for analysis. Details of the Tender Joint Count (TJC), Swolen Joint Count (SJC), Patient Global Assessment (PGA) and ESR were obtained at six weeks, three months, six months and one year. Out of the 69 patients studied 48 were in the mono-therapy group and 21 in the combination therapy group. Methotrexate (MTX) was the most commonly used single DMARD (75%) as well as the most frequent component of the combination groups (85%). The TJC, SJC and PGA analyses of all patients show that DMARDs are effective agents for clinically controlling RA activity. The speed of their beneficial effect is slow and unlike analgesics and NSAIDS, may take up to six weeks to start working. The 6 week responses showed 32.49% improvement in TJC, 33.19% improvement in SJC and 59% better responses in PGA. This response continued to show further improvement and at six months when TJC improved by 63.41%, SJC by 53.21% and PGA with 81% better responses. After 6 months the response reached a plateau but nevertheless maintained until 1 year with improvements in TJC by 66.23%, SJC by 56.48% and PGA with 88.23% better responses. The changes in ESR did not go parallel with the other three outcome measures. The mean baseline ESR of 56 reduced to 44 at 6 weeks but rose again gradually to 54 at 1 year. The sub-group analysis did not show the overall superiority of combination therapy over mono-therapy. DMARDs are effective in controlling disease activity in RA. Their effect starts slowly over 6 week and may take up to 6 months to show full benefits. The beneficial effect was maintained for at least 1 year. Sub-group analysis did not show any advantage of combination therapy over mono-therapy in this series of patients. Methotrexote being the most frequently used DMARDs in both groups and being most cost effective agent seems to be the most useful drug in RA in the developing world.
21794776 [Anti-transglutaminase, antigladin and ultra purified anti-gladin antibodies in patients w 2011 Jan Celiac disease (CD) is an enteric disease caused by dietary gluten in individuals with genetic predisposition. One of the clinical manifestations of CD is the peripheral arthritis that may simulate RA. OBJECTIVE: To determine the frequency of anti-gliadin (aGL), anti-tissue transglutaminase (aTGT) and ultra purified anti-gliadin (AGLU) antibodies in patients with RA. METHODS: Cross-sectional study. We included consecutive patients diagnosed as RA (ACR). Demographic and clinical data was registered by direct interview and serum levels of aGL, aTGT y aGLU were determined using ELISA. RESULTS: Eighty-five RA patients were included; 87% were women. Mean age was 44±12 years, mean disease duration 12 ±9 years. aGL IgG antibodies were positive in 16 patients, IgA aGL antibodies in 29 patients, aGLU in 14 patients and only one patient had aTGT. CONCLUSIONS: It is possible that CD may be the correct diagnosis in a patient with polyarthritis, even if the patient meets the ACR criteria for RA. In other words, CD should be considered among the differential diagnoses in a patient with poly-arthritis.
20467775 A case of adalimumab-associated interstitial pneumonia with rheumatoid arthritis. 2010 Oct A 64-year-old woman with rheumatoid arthritis (RA) began to complain of recurrent non-productive cough 5 months after starting adalimumab. The chest radiograph and high-resolution computed tomographic findings revealed diffuse ground-glass attenuation. Her clinical course suggested that interstitial pneumonia (IP) may have been induced by adalimumab, and she was successfully treated with a medium dose of corticosteroid. This case indicates that adalimumab-associated IP should be considered if a RA patient develops non-productive cough following adalimumab therapy.
20581016 B-cell-activating factor receptor expression on naive and memory B cells: relationship wit 2010 Dec OBJECTIVES: To examine the expression of B-cell-activating factor receptor (BAFF-R) on naive CD27- and memory CD27+ B cells in normal individuals and patients with rheumatoid arthritis (RA) undergoing B-cell depletion therapy with rituximab. PATIENTS AND METHODS: BAFF-R expression on B-cell subsets was determined in normal controls (NC; n = 11), active patients with RA pre-rituximab (pre-RX; n = 15), relapsing patients either concordant for B-cell repopulation (C-R, n = 13) or discordant, with relapse more than 3 months after repopulation (D-R, n = 11) and patients in remission over 3 months postrepopulation (discordant non-relapsing (D-NR), n = 5). Serum BAFF was measured by ELISA and analysed using Mann-Whitney. RESULTS: There was no significant difference between NC, pre-RX and D-NR patients in %BAFF-R-positive B cells or mean fluorescence intensity (MFI) in naive and memory B cells. Relapsing patients had significantly lower MFI and %BAFF-R-positive cells in both naive and memory compartments from NC and pre-RX (C-R and D-R; p < 0.01). BAFF levels in pre-RX patients were within the normal range and did not correlate with BAFF-R expression in any patient group. D-NR patients had relatively lower proportions of pre and postswitch CD27+ B cells than pre-RX patients (D-NR vs pre-RX; p < 0.05 for both) and also lower numbers of postswitch B cells than D-R patients (D-NR vs D-R, p < 0.05). CONCLUSION: BAFF-R expression was significantly reduced on both naive and memory B cells in patients at relapse, regardless of the relationship with B-cell repopulation or serum BAFF levels. Re-establishment of active disease was also associated with an increase in class-switch recombination. Factors responsible for lower levels of BAFF-R may relate to altered thresholds for autoreactive B-cell generation at relapse in patients with RA.
20476867 Tacrolimus for the treatment of active rheumatoid arthritis: a systematic review and meta- 2010 Aug OBJECTIVE: The aim of this study was to assess the efficacy and safety of tacrolimus in patients with active rheumatoid arthritis (RA). METHODS: We surveyed randomized controlled trials (RCTs) and open-label studies that examined the efficacy and toxicity of tacrolimus in disease-modifying anti-rheumatic drug (DMARD)--and methotrexate (MTX)-resistant or -intolerant patients with active RA patients using Medline, the Cochrane Controlled Trials Register, and by performing manual searches. Meta-analysis of RCTs was performed to determine treatment efficacy and safety outcomes. The results are presented as risk ratios (RRs), weighted mean differences (WMDs), or standardized mean differences (SMDs). Open-label studies were included in the systematic review. RESULTS: The four RCTs included 1014 DMARD-resistant or -intolerant patients with DMARD-resistant or -intolerant RA. Median follow-up duration was 6 (range 4-6) months. American College of Rheumatology 20, 50, and 70% (ACR20, ACR50, and ACR70) response rates were significantly higher in the tacrolimus 3 mg/day group (n = 390) than in the controls (n = 402) [primary efficacy outcome, ACR50; risk ratio (RR) 2.583, 95% confidence interval (CI) 1.095-6.092, p = 0.030], and efficacies in the tacrolimus 1.5-2 mg/day group showed a similar pattern. Patients treated with tacrolimus withdrew from treatment because of adverse events (n = 222) (primary safety outcome, withdrawals due to adverse events; RR 1.475, 95% CI 0.895-2.187, p = 0.053) more frequently than controls (n = 231), although this was not significant. All four open-label studies found that tacrolimus was safe, well-tolerated, and provided clinical benefits. CONCLUSIONS: Tacrolimus, at dosages of 1.5-3 mg/day, was found to be effective in DMARD-resistant or -intolerant patients with active RA.
20822708 Risk of tuberculosis in patients with rheumatoid arthritis in Hong Kong--the role of TNF b 2010 Sep OBJECTIVES: To elucidate the incidence rate and relative risk of tuberculosis (TB) in patients with rheumatoid arthritis (RA) compared to the general population in Hong Kong between 2004 and 2008, and to assess whether this risk is associated with exposure to tumour necrosis factor (TNF) blockers after adjusting for other known risk factors. METHODS: We reviewed all the medical records of RA patients to determine the standardised incidence ratio (SIR) of TB in RA patients. Independent explanatory variables associated with active TB in RA were ascertained using the Cox regression model. RESULTS: A total of 2441 RA patients followed at the 5 centres were recruited. The mean age at the start of follow up was 56±14 years. The median follow-up duration was 6,616 and 185 patient-years for the TNF naive and TNF treated groups, respectively. Compared to age- and sex-matched population controls, the SIR of active TB in RA was significantly increased (SIR for TNF naïve RA: 2.35, 95% CI 1.17-4.67, p=0.013, SIR for TNF treated RA: 34.92, 95% CI 8.89-137.20, p<0.001). Independent explanatory variables associated with an increase risk of active TB included older age at study entry (RR 1.05, p=0.013) a past history of pulmonary TB (RR 5.48, p=0.001), extra-pulmonary TB (RR 16.45, p<0.001), Felty's syndrome (RR 43.84, p=0.005), prednisolone>10mg daily (RR 4.44, p=0.009) and the use of TNF blockers (RR 12.48, p<0.001). CONCLUSIONS: Exposure to TNF blockers remained to be an independent risk factor for TB in RA after adjusting for other known risk factors.
19340514 Bronchospasm associated with anti-TNF treatment. 2009 Aug The aetiology of breathing difficulties in patients with inflammatory arthritis being treated with anti-TNF agents can be multi-factorial. Exacerbation of fibrosing alveolitis in patients recently commencing Infliximab has been previously described. Bronchospasm, although reported in some study patients, has not been formally investigated so far. The objective of this study is to define the incidence of bronchospasm in patients treated with anti-TNF agents and investigate details of their respiratory problems. We retrospectively reviewed the notes for 421 patients with inflammatory arthritis being treated with anti-TNF agents at our centre to identify patients who had developed respiratory symptoms during the course of this treatment (cardiac or pleural disease, thromboembolic phenomena or infection were excluded). We identified 7 patients where bronchospasm was thought to be due to treatment with anti-TNF drugs (1.7%). Four of these had to discontinue anti-TNF treatment; two of these needed oral corticosteroid therapy. Two patients were stabilised with increased inhaled beta-2 agonist and steroid, while one patient did not need treatment. All patients had significant exposure to smoking. Bronchospasm is not an uncommon side-effect of anti-TNF treatment. The aetiology of this is probably multi-factorial, but current or previous smoking appears to be a predisposing factor. The frequency and severity of bronchospasm appears to be greater than previously anticipated, all three anti-TNF agents appear to be implicated.
21068383 A bifunctional role for group IIA secreted phospholipase A2 in human rheumatoid fibroblast 2011 Jan 28 Human group IIA-secreted phospholipase A(2) (sPLA(2)-IIA) is an important regulator of cytokine-mediated inflammatory responses in both in vitro and in vivo models of rheumatoid arthritis (RA). However, treatment of RA patients with sPLA(2)-IIA inhibitors shows only transient benefit. Using an activity-impaired sPLA(2)-IIA mutant protein (H48Q), we show that up-regulation of TNF-dependent PGE(2) production and cyclooxygenase-2 (COX-2) induction by exogenous sPLA(2)-IIA in RA fibroblast-like synoviocytes (FLSs) is independent of its enzyme function. Selective cytosolic phospholipase A(2)-α (cPLA(2)-α) inhibitors abrogate TNF/sPLA(2)-IIA-mediated PGE(2) production without affecting COX-2 levels, indicating arachidonic acid (AA) flux to COX-2 occurs exclusively through TNF-mediated activation of cPLA(2)-α. Nonetheless, exogenous sPLA(2)-IIA, but not H48Q, stimulates both AA mobilization from FLSs and microparticle-derived AA release that is not used for COX-2-dependent PGE(2) production. sPLA(2)-IIA-mediated AA production is inhibited by pharmacological blockade of sPLA(2)-IIA but not cPLA(2)-α. Exogenous H48Q alone, like sPLA(2)-IIA, increases COX-2 protein levels without inducing PGE(2) production. Unlike TNF, sPLA(2)-IIA alone does not rapidly mobilize NF-κB or activate phosphorylation of p38 MAPK, two key regulators of COX-2 protein expression, but does activate the ERK1/2 pathway. Thus, sPLA(2)-IIA regulates AA flux through the cPLA(2)-α/COX-2 pathway in RA FLSs by up-regulating steady state levels of these biosynthetic enzymes through an indirect mechanism, rather than direct provision of substrate to the pathway. Inhibitors that have been optimized for their potency in enzyme activity inhibition alone may not adequately block the activity-independent function of sPLA(2)-IIA.
20504294 The prevalence of rheumatic diseases in central Greece: a population survey. 2010 May 26 BACKGROUND: Rheumatic diseases are a major health and financial burden for societies. The prevalence of rheumatic diseases may change over time, and therefore, we sought to estimate the prevalence of rheumatic diseases in an adult population of central Greece. METHODS: In this prospective cross-sectional population survey, a random sample of adult population was drawn from poll catalogues of a region in central Greece. A postal questionnaire was sent to 3,528 people for the presence of any rheumatic disease. All positive cases were further confirmed by clinical examination using the American College of Rheumatoloy criteria. Multiple regression analysis was used to assess risk factors for rheumatic diseases. RESULTS: The response rate was 48.3% (1,705 answers). Four hundred and twenty individuals (24.6%) had a rheumatic disease. The prevalence of rheumatoid arthritis was 0.58% (95% confidence interval [CI], 0.32-0.87), of psoriatic arthritis was 0.35% (95% CI, 0.33-1.13), of ankylosing spondylitis was 0.29% (95% CI, 0.28-0.94), of primary Sjögren's syndrome was 0.23% (95% CI, 0.22-0.75) and of systemic lupus erythematosus was 0.11% (95% CI, 0.11-0.37). One individual had systemic sclerosis (prevalence, 0.058%), 1 individual had dermatomyositis (prevalence, 0.058%; 95% CI, 0.05-0.18), 2 individuals had vasculitis (prevalence 0.11%; 95% CI, 0.11-0.37), 81 individuals had gout (prevalence, 4.75%; 95% CI, 4.41-5.13), and 304 individuals had osteoarthritis (OA) (prevalence 17.82%; 95% CI, 16.50-19.34). Gout was associated with male gender, diabetes mellitus, and hypertension, and OA was associated with age, female gender, and hypertension. CONCLUSIONS: Rheumatic diseases are common in central Greece, affecting nearly a quarter of adult population. OA and gout are the most common joint disorders.
20192982 Comorbidities amongst patients with multiple sclerosis: a population-based controlled stud 2010 Sep BACKGROUND: Data regarding the wide spectrum of comorbidity amongst patients with multiple sclerosis (MS) are still scanty, especially in Asian populations. Our goal was to analyze comorbidity prevalences and risks amongst Chinese patients with MS, compared to matched controls. METHODS: In total, 898 patients with MS and 4490 randomly matched individuals without MS were extracted from the National Health Insurance Research Dataset in Taiwan. We selected 30 comorbid medical conditions for analysis. Conditional logistic regression analyses were used to examine the risks of comorbidity between the two groups. RESULTS: The regression analyses showed that patients with MS were more likely to have systemic lupus erythematosus (OR = 26.9, 95% CI = 10.3-70.3), depression (OR = 6.9, 95% CI = 5.3-8.9), peripheral vascular disorders (OR = 6.6, 95% CI = 4.0-11.0), deficiency anemias (OR = 4.9, 95% CI = 2.8-8.7), rheumatoid arthritis (OR = 4.8, 95% CI = 2.9-8.1) and fluid and electrolyte disorders (OR = 4.8, 95% CI = 2.8-8.3) than the matched controls. CONCLUSIONS: Patients with MS had higher risk of multiple medical comorbidities compared to a matched control group in an ethnic Chinese population.
19270469 Health and physiological effects of an emotional disclosure intervention adapted for appli 2009 BACKGROUND: The efficacy of emotional disclosure in alleviating psychological and physical stress has been well documented in controlled laboratory studies. A next step is to evaluate its clinical utility in 'real world' settings. We adapted the emotional disclosure intervention for use in home-based settings by stimulating the suggested effective ingredients of cognitive-emotional processing, and evaluated its psychological and clinical effectiveness. Reviews indicated the need to examine the physiological changes brought about by emotional disclosure, which may be particularly relevant in immune-mediated diseases. This study was the first to examine neuroendocrine and immune changes after emotional disclosure in patients with rheumatoid arthritis. METHODS: Sixty-eight patients were randomly assigned to four weekly oral emotional disclosure or time management sessions. At baseline and 1 week and 3 months after the sessions, depressed and cheerful mood, joint scores, erythrocyte sedimentation rate, cortisol, noradrenaline, interleukin-6 (IL-6), interferon-gamma (IFN-gamma), and IL-10 were evaluated. Repeated measures analyses of variance were performed. RESULTS: No effect on psychological well-being and clinical outcome was found (p > or = 0.10). Cortisol (p = 0.01) and the serum level of the pro-inflammatory cytokine IFN-gamma (p = 0.05) were differentially affected by the two conditions. The change of IL-6 nearly reached significance (p = 0.07). CONCLUSIONS: The physiological changes are in agreement with theories on the mechanisms underlying emotional disclosure benefits and are suggestive of better disease control after emotional disclosure. General and study-specific reasons for the absence of psychological and clinical effects are discussed. The findings warn against widespread implementation of this home-based emotional disclosure intervention in unselected rheumatoid arthritis samples.
21177334 Heat shock protein 90 maintains the tumour-like character of rheumatoid synovial cells by 2011 May OBJECTIVE: To clarify the contribution of heat shock protein 90 (HSP90) to the pathogenesis of RA, we studied the effects of geldanamycin (GA), an inhibitor of HSP90, on excessive cellular extension and resistance to apoptosis induction of rheumatoid synovial cells. METHODS: Expression of integrin-α5β1 and integrin-linked kinase (ILK) in synovial cells was determined by western blot. The peripheral localization of ILK, reorganization of F-actin, complex formation of ILK with particularly interesting new cysteine-histidine protein (PINCH) and α-parvin, and activation of Rac/cdc42 in synovial cells were examined by using immunohistochemistry and immunoprecipitation. Apoptosis induction by GA treatment was analysed by nuclear staining, cell proliferation assay and western blot of caspase. Effects of GA on mitogen-activated protein kinase (MAPK), PI-3K/protein kinase B (Akt) pathway, mitochondrial Bcl-2 pathway and activation of nuclear factor-κB (NF-κB) were examined by western blot and ELISA. RESULTS: HSP90 was overexpressed in synovial cells while GA decreased the expression of integrin-α5β1 and ILK. The peripheral localization of ILK, reorganization of F-actin, complex formation of ILK with PINCH and α-parvin, and activation of Rac/cdc42 in synovial cells were all inhibited by GA treatment. We found that HSP90 stabilized and regulated the MAPK and PI-3K/Akt pathway, thereby inhibiting HSP90-potentiated synovial apoptosis by stimulating caspases and the mitochondrial Bcl-2 pathway on the one hand and inhibiting the activation of NF-κB on the other. CONCLUSION: The contribution of HSP90 is important in the pathogenesis of RA that potentiates a tumour-like synovial overgrowth by stabilizing ILK, extracellular signal-regulated kinase and Akt.