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ID PMID Title PublicationDate abstract
20155829 Assessment of cognitive function in systemic lupus erythematosus, rheumatoid arthritis, an 2010 May OBJECTIVE: Computerized neuropsychological testing may facilitate screening for cognitive impairment in systemic lupus erythematosus (SLE). This study was undertaken to compare patients with SLE, patients with rheumatoid arthritis (RA), and patients with multiple sclerosis (MS) with healthy controls using the Automated Neuropsychological Assessment Metrics (ANAM). METHODS: Patients with SLE (n = 68), RA (n = 33), and MS (n = 20) were compared with healthy controls (n = 29). Efficiency of cognitive performance on 8 ANAM subtests was examined using throughput (TP), inverse efficiency (IE), and adjusted IE scores. The latter is more sensitive to higher cognitive functions because it adjusts for the impact of simple reaction time on performance. The results were analyzed using O'Brien's generalized least squares test. RESULTS: Control subjects were the most efficient in cognitive performance. MS patients were least efficient overall (as assessed by TP and IE scores) and were less efficient than both SLE patients (P = 0.01) and RA patients (P < 0.01), who did not differ. Adjusted IE scores were similar between SLE patients, RA patients, and controls, reflecting the impact of simple reaction time on cognitive performance. Thus, 50% of SLE patients, 61% of RA patients, and 75% of MS patients had impaired performance on >or=1 ANAM subtest. Only 9% of RA patients and 11% of SLE patients had impaired performance on >or=4 subtests, whereas this was true for 20% of MS patients. CONCLUSION: ANAM is sensitive to cognitive impairment. While such computerized testing may be a valuable screening tool, our results emphasize the lack of specificity of slowed performance as a reliable indicator of impairment of higher cognitive function in SLE patients.
20398001 Genetics in neuroendocrine immunology: implications for rheumatoid arthritis and osteoarth 2010 Apr Both genetic and environmental factors contribute to rheumatoid arthritis (RA) as well as osteoarthritis (OA). For RA, most of the known genetic markers are linked with genes from immunological pathways. Recent genome-wide association studies (GWAS) on RA identified known and novel susceptibility genes like HLA-DRB1, PTPN22, STAT4, TRAF1/C5, OLIG3/TNFAIP3, CD40, CCL21, MMEL1-TNFRSF14, CDK6, PRKCQ, IL2RB, and KIF5A-PIP4K2C. These association signals explain more than 50% of the genetic influence on RA. In contrast, less GWAS data for OA exist. Most OA susceptibility genes arose from classical candidate gene analyses and were not replicated in all study samples. Neuroendocrine factors are hypothesized to play an important role both in RA and OA etiology. Here, we discuss these findings and present an outlook for genetic association studies after GWAS.
19690125 The effect of etanercept on work productivity in patients with early active rheumatoid art 2009 Oct OBJECTIVES: To compare the impact of the combination of etanercept (ETN) and MTX with MTX alone on work productivity among MTX-naïve patients with active early RA over a 12-month period. METHODS: The COMET (COmbination of Methotrexate and ETanercept) trial was a 2-year double-blind randomized clinical trial. Absenteeism during the first year was measured and it included: (i) number of missed workdays; (ii) reduced working time; and (iii) number of stopped workdays. Each absenteeism measure was estimated using a mixed model, and their variations were estimated by bootstrapping. As a sensitivity analysis, the lost workdays due to presenteeism (reduced performance at work) was also estimated. RESULTS: Two hundred and five patients [MTX (n = 100) vs ETN + MTX (n = 105)], who were working full time or part time at baseline and had at least one follow-up observation, were included in the analysis. Compared with the MTX group, the ETN + MTX group had a maximum of 37 fewer missed workdays or at minimum 22 fewer missed workdays. The associated productivity gain equalled 2586 pounds and 1555 pounds, respectively. When additionally accounting for presenteeism, the total improvement could be as high as 42 (95% CI 16, 69) fewer lost workdays representing a productivity gain of 2968 pounds. CONCLUSIONS: Our results demonstrated that early treatment with ETN + MTX led to a significant attenuation of absenteeism among patients with early active RA. These productivity gains represent benefit beyond the traditional measures of clinical and radiographic improvements. Further research to simultaneously measure both absenteeism and presenteeism is warranted.
20929534 Rheumatoid arthritis patients receive less frequent acute reperfusion and secondary preven 2010 INTRODUCTION: The 30-day case-fatality rate after acute myocardial infarction (MI) for rheumatoid arthritis (RA) patients is twice that of the general population. This study compared the frequency and timeliness of early reperfusion therapy and treatment with secondary prevention medications after acute MI in RA patients and controls. METHODS: We performed a structured medical chart review of RA patients and matched controls who had been admitted with acute MI to one of three hospitals in Victoria, Australia, between 1995 and 2005. The administration and timing of acute reperfusion therapy and in-hospital treatment with secondary prevention medications were compared between the two groups. Acute reperfusion was defined as thrombolysis or percutaneous coronary intervention (PCI) within 12 hours of the first symptom of MI. RESULTS: The medical charts of 90 RA patients and 90 matched controls were reviewed. The RA patients were significantly less likely to receive acute reperfusion compared with the controls (16% versus 37%: odds ratio (OR), 0.27; 95% confidence interval (CI), 0.10 to 0.64)), and this difference persisted after adjusting for type of MI, clinical setting of MI, and prior MI (OR, 0.2; 95% CI, 0.05 to 0.6). The RA patients also received less-frequent in-hospital treatment with beta blockers (71% versus 83%; OR, 0.42; 95% CI, 0.18 to 0.96) and lipid-lowering agents (40% versus 70%; OR, 0.21; 95% CI, 0.09 to 0.46). CONCLUSIONS: RA patients who experience acute MI receive acute reperfusion and secondary prevention medications less frequently than do controls. This may contribute to higher case-fatality rates after MI in RA patients.
20099018 Evaluation of abatacept in biologic-naïve patients with active rheumatoid arthritis. 2010 Jun This article reviews the efficacy, safety, and tolerability of abatacept plus methotrexate in patients with active rheumatoid arthritis (RA) and an inadequate response to methotrexate who are naïve to biologic disease-modifying antirheumatic drugs (DMARDs). Data from the randomized, double-blind, placebo-controlled Abatacept in Inadequate Responders to Methotrexate, Abatacept or Infliximab vs Placebo, a Trial for Tolerability, Efficacy, and Safety in Treating Rheumatoid Arthritis, and phase IIb dose-finding trials and their long-term extensions are reviewed. Abatacept plus methotrexate significantly improved clinical responses, physical function, and health-related quality of life compared with methotrexate alone. More patients receiving abatacept plus methotrexate than methotrexate monotherapy achieved a low disease activity state or remission. Radiographic progression of the disease was significantly slowed in the abatacept plus methotrexate arms. Abatacept plus methotrexate was generally well tolerated with no clinically significant safety issues identified. The beneficial effects of abatacept plus methotrexate were sustained long term in extension studies, and no new tolerability or safety issues were evident. Abatacept in combination with methotrexate is an effective, safe, and well-tolerated long-term therapy in biologic-naïve patients with active RA and an inadequate response to methotrexate. Abatacept could be considered as a first-line biologic DMARD in the treatment of RA.
19924704 Detecting gene-environment interactions in genome-wide association data. 2009 Despite the importance of gene-environment (GxE) interactions in the etiology of common diseases, little work has been done to develop methods for detecting these types of interactions in genome-wide association study data. This was the focus of Genetic Analysis Workshop 16 Group 10 contributions, which introduced a variety of new methods for the detection of GxE interactions in both case-control and family-based data using both cross-sectional and longitudinal study designs. Many of these contributions detected significant GxE interactions. Although these interactions have not yet been confirmed, the results suggest the importance of testing for interactions. Issues of sample size, quantifying the environmental exposure, longitudinal data analysis, family-based analysis, selection of the most powerful analysis method, population stratification, and computational expense with respect to testing GxE interactions are discussed.
20199392 Activated synovial macrophages as targets for osteoarthritis drug therapy. 2010 May The great success of targeted biologic therapy against rheumatoid arthritis (RA) in recent years has meant that much research has been devoted to investigating the pathophysiology of osteoarthritis (OA) in the hope of defining novel therapeutic targets. In contrast to RA, with its pannus and erosions, OA has long been thought of as a degenerative disease of cartilage, with secondary bony damage and osteophytes. But in recent years, the importance of the synovium, and in particular the synovial macrophages, in OA, has been highlighted in both in vitro and in vivo studies. This review will discuss the potential of synovial macrophages and their mediators, in particular the proinflammatory cytokines tumour necrosis factor alpha and interleukin-1, as potential therapeutic targets in OA.
18766955 Effect of spironolactone on endothelial dysfunction in rheumatoid arthritis. 2009 Jan OBJECTIVE: Chronic inflammation in rheumatoid arthritis (RA) is associated with vascular endothelial dysfunction. The aim of this study was to determine the effect of spironolactone on endothelial function in anti-tumour necrosis factor (TNF)-naive RA patients. METHODS: Twenty-four anti-TNF-naive RA patients (mean age 49 +/- 1.8 years; disease duration 8.5 +/- 5.8 years) with high disease activity [Disease Activity Score including a 28-joint count (DAS28 > 5.1)] despite treatment with stable doses of conventional disease-modifying anti-rheumatic drugs (DMARDs) were investigated. Inflammatory disease activity [DAS28 and Health Assessment Questionnaire-Disability Index (HAQ-DI) scores, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP)], serum markers of endothelial dysfunction, serum nitrite concentration, and endothelium-dependent and -independent vasodilation of the brachial artery were measured before and after 12 weeks of therapy with oral spironolactone 2 mg/kg/day. RESULTS: After treatment with spironolactone, flow-mediated vasodilation (FMD) improved from 3.18 +/- 0.46% to 3.95 +/- 0.49% (p < 0.001) whereas there was no significant change in endothelium-independent vasodilation with nitroglycerin and baseline diameter (18.4 +/- 1.15% vs. 18.3 +/- 1.13%, p = 0.046, and 3.5 +/- 0.1 vs. 3.52 +/- 0.1 mm, p = 0.952, respectively); serum nitrite concentration was reduced significantly from 6.9 +/- 0.34 to 6.8 +/- 0.33 micromol/L (p < 0.001), ESR from 59.90 +/- 4.86 to 51.22+/-4.26 mm in the first hour (p < 0.001), and CRP level from 15.2+/-3.8 to 9.4+/-2.6 mg/dL (p = 0.019). DAS28 and HAQ-DI scores were significantly reduced, from 6.9+/-0.25 to 4.1+/-0.31 (p < 0.05) and from 1.47+/-0.09 to 0.69+/-0.1 (p < 0.05), respectively. CONCLUSIONS: The study suggests that, in RA, endothelial dysfunction is part of the disease process and treatment with spironolactone improves both endothelial dysfunction and inflammatory disease activity in RA.
19608723 Depression in RA patients treated with anti-TNF is common and under-recognized in the rheu 2009 Sep OBJECTIVES: Depression is common in RA and may be influenced by both disease activity and severity. The aims of this study were to investigate the prevalence of depression in RA patients starting anti-TNF therapy, to investigate how mood alters after exposure to anti-TNF and to determine whether depression is recognized and appropriately managed in the clinic. METHODS: Patients starting anti-TNF therapy were assessed for depression using the Hospital Anxiety and Depression Scale (HADS-D), and classified as depressed with an HADS-D of > or =8. Change in mood was assessed at 6 weeks, 4 months and 12 months. Disease activity data were recorded at baseline, 3 and 12 months. Patients who remained persistently depressed at 4 months had their clinical case notes reviewed to determine whether their low mood had been recognized or treated. RESULTS: Depression was common in this cohort. Depressed patients had higher disease activity scores (DAS28) at all time points, and patients with persistent depression had smaller reductions in DAS28 [median (interquartile range or IQR) change DAS28 1.71 (0-2.6) vs 2.2 (1.5-3.2); P = 0.005]. Only 57% (13/23) patients with persistent depression at 4 months had their depression recognized or managed within the rheumatology clinic. CONCLUSIONS: Depression is common but under-recognized in RA patients starting on anti-TNF therapy. Patients with persistent depression tended to respond less well to anti-TNF, with smaller reductions in DAS28. Given that a significant reduction in DAS28 is a requirement for continuing therapy, recognition and appropriate management of depression may improve TNF effectiveness.
20432503 A novel anti-inflammatory role for secretory phospholipase A2 in immune complex-mediated a 2010 May Phospholipase A2 (PLA2) catalyses the release of arachidonic acid for generation of lipid mediators of inflammation and is crucial in diverse inflammatory processes. The functions of the secretory PLA2 enzymes (sPLA2), numbering nine members in humans, are poorly understood, though they have been shown to participate in lipid mediator generation and the associated inflammation. To further understand the roles of sPLA2 in disease, we quantified the expression of these enzymes in the synovial fluid in rheumatoid arthritis and used gene-deleted mice to examine their contribution in a mouse model of autoimmune erosive inflammatory arthritis. Contrary to expectation, we find that the group V sPLA2 isoform plays a novel anti-inflammatory role that opposes the pro-inflammatory activity of group IIA sPLA2. Mechanistically, group V sPLA2 counter-regulation includes promotion of immune complex clearance by regulating cysteinyl leukotriene synthesis. These observations identify a novel anti-inflammatory function for a PLA2 and identify group V sPLA2 as a potential biotherapeutic for treatment of immune-complex-mediated inflammation.
20595274 Educational interventions for implementation of arthritis clinical practice guidelines in 2010 Aug 1 OBJECTIVE: The dissemination and adoption of clinical practice guidelines (CPG) has been suggested as one method for improving arthritis care delivery. This article provides a review and synthesis of studies evaluating the influence of educational programs designed to implement CPG for osteoarthritis (OA) and rheumatoid arthritis (RA) in primary care. METHODS: A systematic literature search was conducted to identify relevant educational interventions that reported behavioral outcomes that ensured actual knowledge utilization in primary care. A standardized approach was used to assess the quality of the individual studies and a modified version of the Philadelphia Panel methodology allowed for grading of studies based on strength of design, clinical relevance, and statistical significance. RESULTS: The search identified 485 articles; 7 studies were selected for review. In OA, peer facilitated workshops with nurse case-management support for patients decreased the number of referrals to orthopedics by 23%, and educational outreach by trained physicians improved prescribing of analgesics. Interprofessional peer facilitated workshops were successful in increasing referrals to rehabilitation services for people with OA and RA. CONCLUSION: There was sparse literature on educational programs for the implementation of arthritis CPG in the primary care environment. Future studies are needed to evaluate which specific organizational, provider, patient, and system level factors influence the uptake of arthritis CPG in primary care.
20110515 Increased prevalence of carotid artery atherosclerosis in rheumatoid arthritis is artery-s 2010 Apr OBJECTIVE: Cardiovascular (CV) morbidity and mortality are increased in rheumatoid arthritis (RA). Prior investigations of the association of RA with measures of carotid atherosclerosis have yielded conflicting results. We compared carotid intima-media thickness (IMT) of both the common carotid (CCA) and proximal internal carotid (bulb-ICA) arteries, and plaque prevalence, between RA and non-RA participants. METHODS: Subjects with RA were participants in a cohort study of subclinical CV disease in RA. Non-RA controls were selected from the Multi-Ethnic Study of Atherosclerosis. Both groups underwent B-mode ultrasonography of the right and left CCA and bulb-ICA. Linear regression was used to model the association of RA status with CCA and bulb-ICA-IMT, and logistic regression for the association of RA status with plaque. RESULTS: We compared 195 RA patients to 198 non-RA controls. CV risk factors were similarly distributed, except for a higher prevalence of hypertension in the RA group. Mean adjusted bulb-ICA-IMT was higher in RA patients than controls (1.16 vs 1.02 mm, respectively; p < 0.001), while mean adjusted CCA-IMT did not differ significantly. After adjusting for CV risk factors, the odds of plaque were significantly increased in RA participants compared to controls (OR 2.41, 95% CI 1.26-4.61). The association of gender, age, smoking, and hypertension with bulb-ICA-IMT and plaque did not significantly differ by RA status. Interleukin 6 was strongly associated with bulb-ICA-IMT and plaque in controls but not in RA patients. In the RA group, shared epitope was associated with an increased prevalence of plaque. CONCLUSION: Compared to controls, RA was associated with a higher prevalence and higher severity of atherosclerosis in the bulb-ICA but not the CCA. Our data suggest that future studies in RA that utilize carotid artery measurements should include assessment of the bulb-ICA.
20221607 Meta-analysis: diagnostic value of serum anti-mutated citrullinated vimentin antibodies in 2011 Jun Conventional tests are not always helpful in making a diagnosis of rheumatoid arthritis (RA). This study aimed to comprehensively and quantitatively summarize the evidence on the accuracy of anti-mutated citrullinated vimentin (MCV) assay in the diagnosis of RA. A comprehensive meta-review of data on the accuracy of MCV concentrations in the diagnosis of RA were carried out from 16 published studies. Furthermore, receiver operating characteristic curves were used to summarize the overall test performance. The summary estimates for MCV in the diagnosis of RA were: sensitivity 0.77 [95% confidence interval (CI) 0.75-0.78], specificity 0.89 (95% CI 0.87-0.90), positive likelihood ratio (LR+) 7.24 (95% CI 5.60-9.36), negative likelihood ratio (LR-) 0.28 (95% CI 0.23-0.34) and diagnostic odds ratio 29.66 (95% CI 21.09-41.71). The area under the summary receiver operating characteristic curves was 0.92. Data from meta-analysis suggest the accuracy of MCV assay in the diagnosis of RA is high, but ultimately clinician must consider the results of MCV tests combing with other conventional examinations and the clinical feature.
19886992 Sinus aspergilloma in rheumatoid arthritis before or during tumor necrosis factor-alpha an 2009 INTRODUCTION: In 2008, the Food and Drugs Administration required manufacturers of TNFalpha antagonists to strengthen their warnings about the risk of serious fungal infections in patients with rheumatoid arthritis (RA). Sinus aspergilloma occurs occasionally in RA patients and can progress to invasive Aspergillus disease. The purpose of this study was to describe symptomatic sinus aspergilloma in RA patients treated with TNFalpha antagonists. METHODS: Retrospective descriptive study of symptomatic cases of sinus aspergilloma in patients with RA followed in three French university hospitals. A systematic literature review was performed. RESULTS: Among 550 RA patients treated with TNFalpha antagonists, six (1.1%) had symptomatic maxillary aspergilloma diagnosed by computed tomography before or during TNFalpha antagonist therapy. None had chronic neutropenia. Aspergilloma treatment was with surgery only in all six patients. In the literature, we found 20 reports of Aspergillus infection in patients with chronic inflammatory joint diseases (including 10 with RA). Only 5/20 patients were treated with TNFalpha antagonists (invasive lung aspergillosis, n = 3; intracranial aspergillosis, n = 1; and sphenoidal sinusitis, n = 1). CONCLUSIONS: Otorhinolaryngological symptoms must be evaluated before starting or switching TNFalpha antagonists. Routine computed tomography of the sinuses before starting or switching TNFalpha antagonists may deserve consideration.
19953909 [Possible mechanisms of peripheral elevated CD8+ IL-17+ T cells in rheumatoid arthritis]. 2009 Jul 21 OBJECTIVE: To identify interleukin-17 (IL-17 )-producing CD8 positive T cells from patients with rheumatoid arthritis (RA), and investigate its cytokines as well as their correlations. METHODS: Peripheral blood got from 39 RA patients and 40 healthy donors. Flow cytometry was used to analyze the subsets of T cells in peripheral blood from these 39 RA patients and 27 healthy donors. 11-17, IL-6, and IL-23 levels in sera of all these people were tested by ELISA. RESULTS: The median of CD8 IL-17+ T cells from RA patients was 2.7% (95% confidence internal was 1.55%-3.74%); the median of these cells from healthy controls was 1.61% (95% confidence internal was 1.25%-2.61%). CD8+ IL-17+ T cells elevated significantly in RA(P < 0.05). As the production of CD8+ IL-17+ T cells, the IL-17 levels in sera of RA patients and healthy controls were (429 +/- 502) ng/L and (13 +/- 30) ng/L respectively. The IL-17 level in RA is higher than that in healthy people (P < 0.01). Meanwhile, to constitute CD8+ IL-17+ T cell polarizing condition, IL-23 and IL-6 in sera of RA were (157.83 +/- 27.07) ng/L and (32.67 +/- 34.50) x ng/L individually. These two cytokines in healthy controls were (21.97 +/- 3.52) ng/L and (1.82 +/- 1.51) ng/L severally. IL-6 and IL-23 increased clearly in peripheral blood of RA patients as compared with healthy donors (P < 0.01). CONCLUSIONS: This study suggested that elevated CD8+ IL-17+ T cells which involved in IL-17 secretion may depend on increased IL-6 and IL-23 in peripheral blood of rheumatoid arthritis.
20171921 Safety of rituximab in rheumatoid arthritis patients with a history of severe or recurrent 2010 Mar OBJECTIVES: To report our experience with rituximab therapy in patients with rheumatoid arthritis (RA) and a history of severe or recurrent bacterial infections. PATIENTS AND METHODS: Retrospective observational study in five rheumatology departments experienced in the use of biotherapies. Patients were included if they had RA and a history of severe or recurrent bacterial infection (requiring admission and/or intravenous antimicrobial therapy) that contraindicated the introduction or continuation of TNFalpha antagonist therapy. RESULTS: Of 161 RA patients given rituximab in the five study centers, 30 met the inclusion criteria, 23 females and seven males with a mean age of 58.4+/-11.8 years and a mean disease duration of 11.4+/-13.9 years. Among them, 22 had rheumatoid factors and 21 had received TNFalpha antagonist therapy (one agent in 15 patients, two in five patients and three in one patient). Prior infections were as follows: septicemia, n=2; lower respiratory tract infection or lung abscess, n=12; prosthesis infection, n=3; septic arthritis, n=3; endocarditis, n=1; pyelonephritis, n=2; osteitis, n=4; and various skin infections (erysipelas, cellulitis or skin abscess), n=6. Of these 33 infections, 21 occurred during TNFalpha antagonist therapy. During rituximab therapy, all patients received concomitant glucocorticoid therapy (mean dosage, 12+/-7.9 mg/day). The number of rituximab cycles was one in 13 patients, two in seven patients and three or more in 10 patients. Mean time from the single or last serious infection and the first rituximab infusion was 20.1+/-18.7 months. Mean follow-up since the first rituximab infusion was 19.3+/-7.4 months. During follow-up, six (20%) patients experienced one infection each. Immunoglobulin levels after rituximab therapy were within the normal range. CONCLUSION: Rituximab therapy was well tolerated in 24 (80%) of 30 patients with RA and a history of severe or recurrent bacterial infection. In everyday practice, rituximab therapy seems safe with regard to the recurrence of infectious episodes. However, longer follow-ups are needed.
19345885 Elbow arthritis: current concepts. 2009 Apr The purpose of this article is to provide an update and analyze current management, treatment options, and outcomes of elbow arthritis. This article focuses on studies that have been published in the past 5 years. Nonoperative management may provide symptomatic relief in the early stages of the disease process for most patients. Surgical treatment is guided by disease etiology and severity, patient age, and functional demands. Arthroscopic or open synovectomy, debridement arthroplasty, and interposition arthroplasty are generally recommended for the young and active patient population, whereas for low-demand and elderly patients with end-stage painful arthritis, total elbow arthroplasty is considered a more suitable surgical option. Advances in arthroscopic techniques and implant design have led to substantial improvements in treatment of elbow arthritis.
20644721 Modeling the ternary complex TCR-Vbeta/CollagenII(261-273)/HLA-DR4 associated with rheumat 2010 Jul 14 BACKGROUND: It is known that genetic predisposition to rheumatoid arthritis (RA) is associated with the MHC class II allele HLA-DR4 and that residues 261-273 of type II collagen (huCollp261) represent an immunodominant T cell epitope restricted by the DR4 molecule. Despite recent advances in characterization of MHC and T cell receptor (TCR) contacts to this epitope, the atomic details of TCR/huCollp261/HLA-DR4 ternary complex are not known. METHODOLOGY/PRINCIPAL FINDINGS: Here we have used computational modeling to get insight into this interaction. A three-dimensional model of the TCR Vbeta domain from a DR4(+) patient affected by RA has been derived by homology modeling techniques. Subsequently, the structure of the TCR Vbeta domain in complex with huCollp261/HLA-DR4 was obtained from a docking approach in conjunction with a filtering procedure based on biochemical information. The best complex from the docking experiments was then refined by 20 ns of molecular dynamics simulation in explicit water. The predicted model is consistent with available experimental data. Our results indicate that residues 97-101 of CDR3beta are critical for recognition of huCollp261/HLA-DR4 by TCR. We also show that TCR contacts on p/MHC surface affect the conformation of the shared epitope expressed by DR alleles associated with RA susceptibility. CONCLUSIONS/SIGNIFICANCE: This work presents a three-dimensional model for the ternary complex TCR-Vbeta/collagenII(261-273)/HLA-DR4 associated with rheumatoid arthritis that can provide insights into the molecular mechanisms of self reactivity.
20387522 [Miliary tuberculosis and tuberculous peritonitis during infliximab treatment for rheumato 2010 Mar A 55-year-old woman treated with infliximab for rheumatoid arthritis was admitted due to progressive ascites. A CT scan showed massive ascites, bilateral pleural effusion, disseminated granular shadows in the lung, and multiple swollen mediastinal lymph nodes. A FDG-PET/CT scan showed increases of FDG uptake in the mesentery and peritoneum, mimicking peritoneal carcinomatosis. Subsequent pleural and peritoneal fluid analysis showed elevated adenosine deaminase activity levels with no malignant cells. A right pleural biopsy specimen revealed Langhans giant cells and granulomas. Finally, a diagnosis of miliary tuberculosis was established because cultures of the sputum and gastric fluid were positive for Mycobacterium tuberculosis. Several weeks after a standard anti-tuberculosis regimen with 4 drugs was initiated, her clinical condition and radiological findings ameliorated. Since the initial manifestations of tuberculosis tend to be more severe during treatment of rheumatoid arthritis with tumor necrosis factor-alpha inhibitors such as infliximab due to immune suppression, we should pay closer attention to the possibility of tuberculosis infection in these patients.
20388503 Automated analysis of the serum antioxidative activities against five different reactive o 2010 Aug 5 BACKGROUND: There is a growing evidence that reactive oxygen species (ROS) may cause many pathologic conditions including chronic diseases, neurodegenerative disorders, cancer and aging. There are a number of methods to measure the total antioxidative activity of the serum. However, since the lifetime and oxidative activity of various types of ROS are all different, to measure simply the total antioxidative activity of the serum is not enough. Therefore, to aid the diagnosis and to improve the therapeutic strategy, it is important to develop a simple and reliable method of assaying antioxidative activity of the serum. METHODS: A method that combines sequential injection analysis (SIA) and luminol chemiluminescence (CL) detection was employed for the measurement of antioxidative activities of human serum. We collected sera from healthy subjects (n=42) and patients with diabetes (n=39) and rheumatoid arthritis (n=25) and tested the sensitivity, reproducibility and reliability of our method. RESULTS: Since the operation is automatically controlled by a personal computer, we obtained a satisfactory repeatability without the need of much manpower. The time required for obtaining the antioxidative activity against one ROS for one individual is less than 3min. Although the value of antioxidative activity varies from subject to subject, there were a certain relationship between the disease and the antioxidative values of each type of ROS. The results suggest that the measurement of antioxidative activity against different ROS may provide us with valuable information regarding the disease state. CONCLUSIONS: The evaluation of antioxidative activities against each ROS by the proposed method should be more informative to understand the antioxidative status of biological fluid.