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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
17968878 Protease-activated receptor 2 mediates the proinflammatory effects of synovial mast cells. 2007 Nov OBJECTIVE: Mast cells are hypothesized to play a role in the pathogenesis of rheumatoid arthritis (RA) by mechanisms requiring elucidation. Tryptase released from these cells can activate protease-activated receptor 2 (PAR-2), which was recently shown to have proinflammatory actions. The purpose of this study was to examine the relationship between synovial mast cells and PAR-2. Mast cell proximity to PAR-2-expressing cells was investigated in RA synovium. In murine studies, we assessed the capacity of mast cell tryptase to mediate synovial proinflammatory responses via PAR-2 and whether degranulating mast cells induced synovial hyperemia by PAR-2 activation. METHODS: RA synovial tissue was examined by immunohistochemistry. PAR-2(+/+) and PAR-2(-/-) C57BL/6J mice were used to investigate the PAR-2 dependence of compound 48/80-induced synovial hyperemia, as measured by laser Doppler imaging, and joint swelling and hyperemic responses to recombinant human beta-tryptase. RESULTS: Mast cells and synovial lining cells staining for PAR-2 were colocalized in RA articular tissue. Compound 48/80 administration resulted in vasodilatation in PAR-2(+/+) mice but not in PAR-2(-/-) mice, which showed a vasoconstrictor response. Eliminating the 5-hydroxytryptamine-mediated component of this response with methysergide unveiled an enhanced PAR-2-mediated vasodilatation to compound 48/80 in PAR-2(+/+) mice and ablated the vasoconstrictor response in PAR-2(-/-) mice. Treatment with beta-tryptase resulted in dose-dependent knee joint swelling and synovial vasodilatation in PAR-2(+/+) mice but not PAR-2(-/-) mice. CONCLUSION: This in vivo study is the first to explore the relationship between synovial mast cells and PAR-2. Our results support the hypothesis that mast cells contribute to the pathogenesis of inflammatory arthritis through PAR-2 activation via release of mast cell tryptase.
18412313 Relative responsiveness of physician/assessor-derived and patient-derived core set measure 2008 May OBJECTIVE: We assessed whether individual American College of Rheumatology core set measures (CSM), and the CSM grouped as composite patient-derived (CPD) or composite physician/assessor-derived (CMD), performed differently in rheumatoid arthritis (RA) clinical trials. METHODS: We used data from 9 RA trials [anti-tumor necrosis factor-alpha (TNF-alpha) and disease modifying antirheumatic drug (DMARD)] in which CSM had been assessed, conducted from the early 1990s to present, with a total of 2969 patients. We grouped the CSM as CPD (pain, patient global assessment, function) and CMD [tender joint count (TJC), swollen joint count (SJC), physician global, inflammatory marker]. Using bootstrap simulation, we estimated the sample size that would be required to distinguish active treatment from placebo with the Wilcoxon rank-sum test in the clinical trials for the outcomes of percentage change of each individual CSM, of the Disease Activity Score (DAS), and average percentage change of the CMD or of the CPD. RESULTS: Comparing the performance of individual CSM relative to one another, the physician and patient global assessments and TJC would require the lowest sample sizes to distinguish active treatment from placebo, while use of the SJC, inflammatory marker, and function would require the highest. The CMD performed similarly to the DAS, requiring similar sample sizes, while the CPD would require 1.7 times greater sample size to distinguish treatment from placebo. The results were similar across DMARD and anti-TNF-alpha trials. CONCLUSION: Because of their demonstrated sensitivity to change, composite measures assessing RA outcomes in clinical trials should continue to include physician/assessor-derived core set measure assessments.
18519424 Laboratory and febrile features after joint surgery in patients with rheumatoid arthritis 2009 May OBJECTIVES: To understand the acute phase responses to surgical intervention in patients with rheumatoid arthritis (RA) treated with the anti-interleukin (IL)6 receptor antibody, tocilizumab. METHODS: In a retrospective 1:1 pair-matched case-control study, 22 tocilizumab-treated RA cases and 22 cases treated with conventional disease-modifying antirheumatic drugs (DMARDs) and matched for type of surgery, age and sex were evaluated for body temperature every day, and blood C-reactive protein (CRP) levels and white blood cell (WBC), neutrophil and lymphocyte counts on days -1, 1, 3 and weeks 1 and 2 after joint surgery. Safety issues were also monitored. RESULTS: No complications of infection or delay of wound healing occurred in either patient group. Tocilizumab partially, but significantly, suppressed the increase in body temperature on postoperative days 1 and 2, compared with DMARDs (average (SD) maximum increase in temperature was 0.45 (0.1) degrees C in the tocilizumab group and 0.78 (0.1) degrees C in the DMARD group; p<0.01). Tocilizumab completely suppressed the increase in CRP after surgery, whereas all cases treated with DMARDs showed a significant increase of CRP at postoperative day 1 (5.5 (0.6) mg/dl; p<0.001). WBC, neutrophil and lymphocyte counts showed no remarkable change after surgery, and there was no significant difference in any cell counts between the patient groups. CONCLUSIONS: Within this small number of cases, safe operations on patients were performed during tocilizumab treatment. Tocilizumab suppressed fever and increase of CRP after surgery, whereas there was no influence on the transition in number of leukocytes. This characteristic postoperative response should be considered during tocilizumab treatment.
17322964 Effects of dynamic exercise on circulating IGF-1 and IGFBP-3 levels in patients with rheum 2007 Oct This study was performed to determine the effects of short-term dynamic exercise on serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) levels in the patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Patients with RA or AS and healthy controls were recruited. Dynamic treadmill exercise therapy was accomplished for 20 min/session with all of the participants. There were five sessions per week for 2 weeks. Morning stiffness duration, body pain, Stanford health assessment questionnaire, Ritchie articular index, Bath ankylosing spondylitis disease activity index (BASDAI), and Bath ankylosing spondylitis functional index (BASFI) were evaluated in the RA and AS patients. Laboratory assessments included: erythrocyte sedimentation rate, serum C-reactive protein, IGF-1, and IGFBP-3. Clinical and laboratory assessments were recorded at baseline and during exercise treatment on days 7 and 15. Twenty patients with RA, 15 with AS, and 14 healthy controls were included in this study. The pain evaluation, Ritchie, BASDAI, and BASFI scores were significantly improved by the exercise treatment in both patient groups. The important increases were found in circulating IGF-1 in RA (p < 0.001) and AS (p = 0.001) at the end of 2 weeks. In control individuals, serum IGF-1 levels showed a significant decline in the first week (p < 0.05). No significant changes were observed on serum IGFBP-3 levels. Our data suggest that serum IGF-1 levels are increased by the dynamic exercise program in RA and AS patients. The increased IGF-1 may play an important role in the beneficial effects of dynamic exercise therapy in these patients.
16395748 A multicenter, double-blind, randomized, placebo controlled trial of infliximab combined w 2006 Jan OBJECTIVE: A placebo controlled, double-blind trial (DBT) was conducted for Japanese patients with active rheumatoid arthritis (RA) despite treatment with low dose methotrexate (MTX) to evaluate the efficacy and safety of infliximab. Extended treatment with infliximab was conducted in an open-label trial (OLT). METHODS: In the DBT, 147 patients were randomly assigned and treated with a placebo or 3 mg/kg or 10 mg/kg infliximab at Weeks 0, 2 and 6, combined with MTX. In the OLT, 129 patients from the DBT received 3 mg/kg infliximab every 8 weeks. RESULTS: The mean dose of MTX was 7.2 +/- 2.0 mg/week. Significantly more patients receiving 3 mg/kg (61.2%) and 10 mg/kg (52.9%)infliximab achieved a 20% improvement according to the American College of Rheumatology (ACR) criteria at Week 14, compared to placebo (23.4%) (p < 0.001). There was no significant difference in incidence of adverse events among the treatment groups. In patients receiving infliximab in the DBT, 11.6% of patients with serum infliximab just before the OLT developed antibodies to infliximab (ATI) in the OLT, whereas 62.2% of patients without serum infliximab did. In patients receiving placebo in the DBT, 43.9% developed ATI. CONCLUSION: The efficacy and safety of infliximab combined with low dose MTX were similar to those of the ATTRACT study. The data from the DBT and OLT also supported the importance of an induction treatment of infliximab, followed by a maintenance treatment without a long interval, giving stable serum concentrations in order to prevent formation of ATI.
18605522 Connective tissue disorders and the mouth. 2008 Jun The connective tissue disorders frequently give rise to orofacial manifestations, especially dry mouth because of Sjögren's syndrome. In addition, the systemic complications of such diseases may impact upon the provision of oral health care. The present article reviews the consequences of connective tissue disorders of relevance to oral health care providers. CLINICAL RELEVANCE: Connective tissue disorders can give rise to oral manifestations and systemic complications that may occasionally compromise primary oral health care.
18990945 Alpha-methylprednisolone conjugated cyclodextrin polymer-based nanoparticles for rheumatoi 2008 A glycinate derivative of alpha-methylprednisolone (MP) was prepared and conjugated to a linear cyclodextrin polymer (CDP) with a loading of 12.4% w/w. The polymer conjugate (CDP-MP) self-assembled into nanoparticles with a size of 27 nm. Release kinetics of MP from the polymer conjugate showed a half-life (t1/2) of 50 h in phosphate buffer solution (PBS) and 19 h in human plasma. In vitro, the proliferation of human lymphocytes was suppressed to a similar extent but with a delayed effect when CDP-MP was compared with free MP. In vivo, CDP-MP was administered intravenously to mice with collagen-induced arthritis and compared with free MP. CDP-MP was administered weekly for six weeks (0.07, 0.7, and 7 mg/kg/week) and MP was administered daily for six weeks (0.01, 0.1, and 1 mg/kg/day). Body weight changes were minimal in all animals. After 28 days, a significant decrease in arthritis score was observed in animals treated weekly with an intermediate or high dose of CDP-MP. Additionally, dorsoplantar swelling was reduced to baseline in animals treated with CDP-MP at the intermediate and high dose level. Histological evaluation showed a reduction in synovitis, pannus formation and disruption of architecture at the highest dose level of CDP-MP. MP administered daily at equivalent cumulative doses showed minimal efficacy in this model. This study demonstrates that conjugation of MP to a cyclodextrin-polymer may improve its efficacy, leading to lower doses and less frequent administration for a safer and more convenient management of rheumatoid arthritis.
18324587 [Lapidus procedure in patients with rheumatoid arthritis--short-term results]. 2008 Jan AIM: Hallux valgus combined with flat foot is one of the most common foot deformities affecting patients with rheumatoid arthritis. The Lapidus procedure is indicated when the hallux valgus angle is more than 15 degrees or the first tarsometatarsal joint is hypermobile. We aimed to evaluate the results of the Lapidus procedure in patients with rheumatoid arthritis. METHOD: We performed the Lapidus procedure in 31 patients between 2002 and 2005. In ten patients we performed a bilateral procedure and in ten patients we performed a single Lapidus procedure. In 27 cases we combined the procedure with a resection of the second-fifth metatarsal heads (Hoffmann procedure), in four cases with a Weil osteotomy of the second-fifth metatarsal necks. We performed an excision of the articular surface of the first metatarsal head (Mayo) in 10 patients, a Keller resection procedure in 9 patients, an arthrodesis of the first metatarsophalangeal joint in 3 patients, and an Akin wedge osteotomy of the proximal phalanx of the thumb in 3 patients. Arthrodesis was fixed by two K-wires in 5 cases, by 2 compression screws in 7 cases, and in thirty-four cases we used memory staples. RESULTS: We evaluated the outcomes of forty-one procedures in thirty-one patients (24 female, 7 male). The averge age at surgery was 54.3 years. Thirty-two feet were without pain after the procedures, in five cases the patients felt moderate pain in the dorsal part of the foot and in four cases the patients felt pain in the transverse arch of foot. Complications included delayed primary wound closure in five cases, in one case we performed a revision procedure for a deep infection. Delayed hallux valgus developed in 5 cases. The mean first intermetatarsal angle before surgery was 19.5 degrees (range 12 - 27 degrees) and improved to 8 degrees after surgery. In 3 cases we found an unsatisfactory intermetatarsal angle correction with partial renewal of the hallux valgus. CONCLUSION: A correctly performed Lapidus procedure enables correction of the varus position of 1st metatarsus and hallux valgus.
18677010 Associations of obesity with modifiable risk factors for the development of cardiovascular 2009 Feb OBJECTIVES: To assess the association of body mass index (BMI) with modifiable cardiovascular disease (CVD) risk factors in patients with rheumatoid arthritis (RA). METHODS: BMI, disease activity, selected CVD risk factors and CVD medication were assessed in 378 (276 women) patients with RA. Patients exceeding accepted thresholds in >or=3 CVD risk factors were classified as having the metabolic syndrome (MetS). RESULTS: BMI independently associated with hypertension (OR = 1.28 (95% CI = 1.22 to 1.34); p = 0.001), high-density lipoprotein (OR = 1.10 (95% CI = 1.06 to 1.15); p = 0.025), insulin resistance (OR = 1.13 (95% CI = 1.08 to 1.18); p = 0.000) and MetS (OR = 1.15 (95% CI = 1.08 to 1.21); p = 0.000). In multivariable analyses, BMI had the strongest associations with CVD risk factors (F(1-354) = 8.663, p = 0.000), and this was followed by lipid-lowering treatment (F(1-354) = 7.651, p = 0.000), age (F(1-354) = 7.541, p = 0.000), antihypertensive treatment (F(1-354) = 4.997, p = 0.000) and gender (F(1-354) = 4.707, p = 0.000). Prevalence of hypertension (p = 0.004), insulin resistance (p = 0.005) and MetS (p = 0.000) was significantly different between patients with RA who were normal, overweight and obese, and BMI differed significantly according to the number of risk factors present (p = 0.000). CONCLUSIONS: Increasing BMI associates with increased CVD risk independently of many confounders. RA-specific BMI cut-off points better identify patients with RA at increased CVD risk. Weight-loss regimens should be developed and applied in order to reduce CVD in patients with RA.
18412311 The problem of rheumatoid arthritis disease activity and remission in clinical practice. 2008 Jun OBJECTIVE: To investigate the results and feasibility of available scales to measure minimal disease activity (MDA) and remission in rheumatoid arthritis (RA) in the clinic. METHODS: We studied 849 consecutive patients with RA seen in a community rheumatology practice for routine RA care by 4 rheumatologists, beginning in March 2007 and ending in August 2007. Patients and physicians completed a simple form at each visit. We calculated the Disease Activity Score 28 (DAS28), Clinical Disease Activity Index (CDAI), physician assessment of global activity, and the Patient Activity Scale (PAS-II). From these we calculated remission and MDA prevalence in this community practice. RESULTS: The DAS28 could not be determined in more than 50% of patients because of referring physician and insurance company restrictions. Remission prevalences differed by assessment method: DAS28 28.5%, CDAI 6.5%-8.1%, physician global 12.5%, PAS 13.7%. MDA was 26.9% using the American College of Rheumatology core set variables, 34.7% using the DAS28, and 26.8% using the PAS-II. The kappa statistic was only fair (0.2 to 0.4) for most comparisons between assessment methods. No significant differences were noted for remission and MDA according to biologic therapy. CONCLUSION: The CDAI and/or physician global and PAS-II are simple acceptable ways to measure RA activity in the clinic, but results differ strikingly according to method. Further standardization appears to be required for full implementation of the CDAI. Caution is urged before using these methods for regulatory purposes.
17589595 Positive associations of serum concentration of polychlorinated biphenyls or organochlorin 2007 Jun BACKGROUND: Persistent organic pollutants (POPs) can influence the immune system, possibly increasing the risk of rheumatoid arthritis (RA). In addition, as metabolic change due to obesity has been proposed as one mechanism of osteoarthritis (OA), POPs stored in adipose tissue may be also associated with OA. OBJECTIVE: Our goal in this study was to examine associations of background exposure to POPs with arthritis among the general population. DESIGN: We investigated cross-sectional associations of serum POPs concentrations with the prevalence of self-reported arthritis in 1,721 adults >/= 20 years of age in the National Health and Nutrition Examination Survey 1999-2002. RESULTS: Among several POPs, dioxin-like polychlorinated biphenyls (PCBs) or nondioxin-like PCBs were positively associated with arthritis in women. After adjusting for possible confounders, odds ratios (ORs) were 1.0, 2.1, 3.5, and 2.9 across quartiles of dioxin-like PCBs (p for trend = 0.02). Corresponding figures for nondioxin-like PCBs were 1.0, 1.6, 2.6, and 2.5 (p for trend = 0.02). Organochlorine (OC) pesticides were also weakly associated with arthritis in women. For subtypes of arthritis, respectively, RA was more strongly associated with PCBs than was OA. The adjusted ORs for RA were 1.0, 7.6, 6.1, and 8.5 for dioxin-like PCBs (p for trend = 0.05), 1.0, 2.2, 4.4, and 5.4 for nondioxin-like PCBs (p for trend < 0.01), and 1.0, 2.8, 2.7, and 3.5 for OC pesticides (p for trend = 0.15). POPs in men did not show any clear relation with arthritis. CONCLUSIONS: The possibility that background exposure to PCBs may be involved in pathogenesis of arthritis, especially RA, in women should be investigated in prospective studies.
18609264 The relationship between anti-cyclic citrullinated peptide and bone mineral density and ra 2008 Sep OBJECTIVES: We aimed to investigate the relationship between anti-cyclic citrullinated peptide (anti-CCP) levels and bone mineral density (BMD), bone turnover, and radiographic damage in patients with rheumatoid arthritis (RA). METHODS: Eighty patients (68 females, 12 males, mean age 46.50+/-14.59 years) with RA were included in the study. Anti-CCP antibodies were measured by enzyme-linked immunosorbent assay (ELISA). Bone turnover was studied by analysing serum levels of C-terminal telopeptide of type I collagen (sCTX, ng/mL), using an enzyme immunoassay. BMD was measured by dual-energy X-ray absorptiometry (DXA). Disease activity was assessed according to the Disease Activity Score that includes 28 joint counts (DAS28). Functional capacity was assessed by the Health Assessment Questionnaire (HAQ). RESULTS: Anti-CCP-positive patients were defined as group 1 and anti-CCP-negative patients as group 2. The mean disease duration was 7.53+/-6.27 years in group 1 and 6.25+/-6.51 years in group 2. Anti-CCP had a limited negative correlation with lumbar BMD (r = -0.220, p = 0.050) and a negative correlation with femoral BMD (r = -0.242, p = 0.031). There was no statistically significant correlation between anti-CCP and sCTX values (r = 0.117, p = 0.301). Sharp scores were significantly higher in anti-CCP-positive than anti-CCP-negative patients (p = 0.012), and anti-CCP levels were significantly correlated with Sharp scores (r = 0.240, p = 0.032). CONCLUSIONS: We found that RA patients with higher levels of anti-CCP antibody had lower lumbar and femoral BMD. Anti-CCP levels were also associated with radiographic damage. Therefore, we suggest that anti-CCP may be a determinant of bone loss in patients with RA.
17079158 Increased adiponectin is negatively linked to the local inflammatory process in patients w 2006 Sep Adiponectin has been shown to exert insulin-sensitizing, anti-atherogenic, and anti-inflammatory properties in metabolic diseases. It has been suggested that adiponectin may play a role in rheumatoid arthritis (RA). To assess adiponectin in serum and synovial fluid from patients with RA and osteoarthritis (OA), and in serum from healthy controls. Adiponectin and CRP levels were analyzed by ELISA. The clinical activity of RA patients was assessed according to the 28 joint count Disease Activity Score. Synovial fluid adiponectin was significantly higher in RA than in OA patients (p<0.001). Adiponectin was negatively associated with the leukocyte count in RA synovial fluid (r=-0.45, p<0.05). Serum adiponectin was higher in RA compared to healthy controls (p<0.02), however comparable to OA patients. Serum adiponectin was higher than in synovial fluid in both diseases (p<0.001). In general, women had higher adiponectin levels than men. Adiponectin was not related to age, disease duration, body mass index, or disease activity of RA patients. Adiponectin is decreased in synovial fluid compared to serum indicating that peripheral fat stores are major producers of adiponectin into the blood stream. However, increased synovial fluid adiponectin in RA patients may counterpart the local inflammatory process.
18728132 Validity and responsiveness of the Rehabilitation Activities Profile (RAP) in patients wit 2008 Sep OBJECTIVE: To investigate the internal consistency, validity and responsiveness of the Rehabilitation Activities Profile (RAP; a rehabilitation tool structuring the multidisciplinary team care process) in patients with rheumatoid arthritis. METHODS: In 85 rheumatoid arthritis patients admitted to a rheumatology clinic the RAP was applied at admission, at discharge, and six weeks thereafter. Additional assessments included measures of physical and psychological functioning, disease activity and quality of life. The internal consistency of the RAP was determined with Cronbach's alpha. Associations between the RAP and other outcome measures were determined by Spearman rank correlation coefficients. Responsiveness measures included the standardized response mean (SRM), effect size (ES) and responsiveness ratio (RR). RESULTS: Cronbach's alpha of the RAP total score was 0.78. The RAP total score correlated significantly with all other outcome measures. The mean RAP total score improved from 15.2 to 13.2 at discharge (change -2.0; 95% confidence interval (CI) -3.4 to -0.7) and to 11.5 (change -3.7; 95% CI -3.9 to -1.5) six weeks thereafter. The responsiveness of the RAP total score was low (standardized response mean -0.34, effect size -0.30) to high (responsiveness ratio -0.87) at discharge and moderate (standardized response mean -0.54, effect size -0.55) to high (responsiveness ratio -1.56) six weeks thereafter. CONCLUSIONS: The RAP appeared to be an internally consistent, valid and responsive measure to reflect limitations on the level of activities and participation in patients with rheumatoid arthritis admitted for multidisciplinary team care.
17464608 Charnley low-frictional torque arthroplasty in young rheumatoid and juvenile rheumatoid ar 2007 Apr INTRODUCTION: In the early 1960s, Charnley was cautious with his patient selection for total hip replacement. As follow-up increased and confidence in the operation grew, younger patients were selected. We present our results of the Charnley LFA in young patients with rheumatoid and juvenile rheumatoid arthritis with a followup of up to 36 years. PATIENTS: We studied 292 Charnley low-friction arthroplasties in 195 young patients with an established diagnosis of rheumatoid arthritis. Their mean age at operation was 38 (12-50) years; 168 (58%) were receiving steroids and 79 (27%) were on non-steroidal antiinflammatory medication. The mean follow-up for the whole group was 15 (1-36) years. 24 patients could not be traced (33 hips), and 61 patients died (88 hips). RESULTS: 25 patients (41 hips) had had a revision. The main indication for revision was cup loosening. In the 85 patients (130 hips) attending follow-up, their mean age at surgery was 36 (17-50) years and the mean follow-up was 20 (10-36) years. 98% were pain-free or had no more than occasional discomfort, 44% claimed to have normal or near-normal function, while 62% had full or almost full range of movement of the replaced hip. Radiographically, 29 cups (22%) were considered to be loose. 1 stem (1%) was definitely loose and 2 stems (2%) were probably loose. With revision for any indication as the endpoint, the survival was 74% at 25 years follow-up. INTERPRETATION: The Charnley LFA continues to be an excellent hip replacement, even for very young rheumatoid arthritis patients. Wear and aseptic cup loosening are the main long-term problems.
18278841 The validity and responsiveness of generic utility measures in rheumatoid arthritis: a rev 2008 Apr OBJECTIVE: Cost-utility analysis is increasingly important as healthcare providers aim to invest scarce resources in interventions offering the greatest health benefit. The ability to attach utility values to health states is essential, and is increasingly performed using generic scales. However, the evidence regarding the validity of generic utility scales in rheumatoid arthritis (RA) is unclear. We summarize and review evidence on the validity and comparative performance of generic utility scales in RA. METHODS: We searched the English-language medical literature for studies using utilities in RA between 1980 and mid-2006. Reports describing primary evidence of the validity or performance of a generic utility scale in RA were selected, summarized, and reviewed using the OMERACT filter. RESULTS: In total 923 articles were identified, of which 228 reported the use of utility scales in RA; 26 studies related to the validation or evidence of generic utility scales in RA, the EQ-5D, Health Utility Index-2 (HUI2) and HUI3, SF-6D, and Quality of Well-Being Scale. The EQ-5D, HUI2 and HUI3, and SF-6D all have consistent evidence of construct validity and responsiveness in RA, but each has limitations. CONCLUSION: The EQ-5D and HUI3 have been the most extensively studied instruments and show validity and responsiveness for use in RA, but both instruments have limitations. The SF-6D is relatively new and appears to have potential for use in milder RA, but needs further evaluation. More longitudinal head-to-head evaluation of measures is needed across the spectrum of RA disease severity to further investigate their comparative properties, and to seek consensus on the best utility measure for use in economic evaluation.
16877603 The management of failed ankle replacement. 2006 Aug Advances in the design of the components for total ankle replacement have led to a resurgence of interest in this procedure. Between January 1999 and December 2004, 16 patients with a failed total ankle replacement were referred to our unit. In the presence of infection, a two-stage salvage procedure was planned. The first involved the removal of the components and the insertion of a cement spacer. Definitive treatment options included hindfoot fusion with a circular frame or amputation. When there was no infection, a one-stage salvage procedure was planned. Options included hindfoot fusion with an intramedullary nail or revision total ankle replacement. When there was suspicion of infection, a percutaneous biopsy was performed. The patients were followed up for a minimum of 12 months. Of the 16 patients, 14 had aseptic loosening, five of whom underwent a revision total ankle replacement and nine a hindfoot fusion. Of the two with infection, one underwent fusion and the other a below-knee amputation. There were no cases of wound breakdown, nonunion or malunion. Management of the failed total ankle replacement should be performed by experienced surgeons and ideally in units where multidisciplinary support is available. Currently, a hindfoot fusion appears to be preferable to a revision total ankle replacement.
17330254 Glucocorticoids and cardiovascular events in rheumatoid arthritis: a population-based coho 2007 Mar OBJECTIVE: To determine the relationship between glucocorticoid exposure and cardiovascular (CV) events in patients with rheumatoid arthritis (RA). METHODS: A total of 603 adult residents of Rochester, Minnesota with incident RA between 1955 and 1995 were followed up through their medical records for a median of 13 years (total of 9,066 person-years). Glucocorticoid exposure was defined 3 ways: tertiles of cumulative exposure; recent use (< or =3 months) versus past use (>3 months); and average daily dosage (< or =7.5 mg/day or >7.5 mg/day). CV events, including myocardial infarction, heart failure, and death from CV causes, were defined according to validated criteria. Cox regression models were adjusted for demographic features, CV risk factors, and RA characteristics. RESULTS: Rheumatoid factor (RF)-negative patients with exposure to glucocorticoids were not at increased risk of CV events, irrespective of the glucocorticoid dosage or timing of use, as compared with the reference group of RF-negative patients who had never been exposed to glucocorticoids. In contrast, RF-positive patients were at increased risk of CV events, particularly with higher cumulative exposure, higher average daily dosage, and recent use of glucocorticoids. RF-positive patients with high cumulative exposure to glucocorticoids had a 3-fold increased risk of CV events (hazard ratio 3.06 [95% confidence interval 1.81-5.18]), whereas RF-negative patients with high cumulative exposure were not at increased risk (hazard ratio 0.85 [95% confidence interval 0.39-1.87]). CONCLUSION: RF-positive but not RF-negative patients were at increased risk of CV events following exposure to glucocorticoids. These findings suggest that glucocorticoids interact with RF status to modulate the occurrence of CV events in patients with RA. The mechanisms underlying this interaction are unknown and should be the subject of further research.
18799087 Inhibitory effect of synthetic cannabinoids on cytokine production in rheumatoid fibroblas 2008 Jul OBJECTIVE: To verify whether synthetic cannabinoids (CP55,940 and WIN55,212-2) are able to exert an anti-inflammatory effect on rheumatoid fibroblast-like synoviocytes (FLS) by down-regulating cytokine production, and determine whether this effect could be mediated by CB1/CB2 cannabinoid receptors. METHODS: Interleukin-6 (IL-6) and interleukin-8 (IL-8) were assayed in the supernatant from cultured FLS by ELISA method before and after 3 hours of incubation with CP55,940 (10 microM) and WIN55,212-2 (10 microM). Co-stimulation of cells with the cannabinoid receptor antagonists was performed to evaluate receptor involvement in cytokine modulation. All the experiments were conducted in basal conditions and after 1 hour pre-incubation with 0.1 ng/ml IL-1beta. FLS expression of CB1 and CB2 receptor was studied by Western Blot analyses. RESULTS: Both CP55,940 and WIN55,212-2 induced a potent and significant reduction in IL-6 and IL-8 secretion from IL-1beta. stimulated FLS. Although FLS express CB1 and CB2 receptor, cannabinoid receptor antagonists did not significantly modify the inhibition of cytokines secretion induced by CP55,940 and WIN55,212-2. CONCLUSIONS: In vitro, CP55,940 and WIN55,212-2 exert a potent anti-inflammatory effect on rheumatoid FLS via a non-CB1/CB2 receptor mediated mechanism.
18536334 [Case of miliary tuberculosis during treatment with infliximab for rheumatoid arthritis]. 2008 May A 70-year-old woman afflicted with rheumatoid arthritis was consulted another hospital because of fever and abnormality in chest X-ray. She had been treated with methotrexate and infliximab for seven months. She was diagnosed as methotrexate-induced pneumonia, and was administrated large therapeutic doses of corticosteroid, but finding of her chest X-ray exacerbated. Her sputum examination was positive for Mycobacterium tuberculosis complex by nucleic-acid amplification test, and she was diagnosed as miliary tuberculosis. She was treated with INH, RFP, EB, and PZA, and showed good clinical response to treatment. When infliximab is prescribed, we have to bear in mind possible complication of tuberculosis.