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ID PMID Title PublicationDate abstract
19330599 Galectin-2 (LGALS2) 3279C/T polymorphism may be independently associated with diastolic bl 2009 Apr The galectin-2 (LGALS2) 3279 C/T single nucleotide polymorphism (SNP) has recently been associated with myocardial infarction (MI). Although hypertension, a very prevalent entity in rheumatoid arthritis (RA), is one of the greatest risk factors for MI, the possible association of LGALS2 3279 C/T and hypertension has not been investigated. We genotyped 386 RA patients, 272 hypertensives and 114 normotensives. Diastolic blood pressure (DBP) was significantly lower in TT compared to CC homozygotes (-4.11 mmHg, p = 0.044) even when adjusted for multiple confounders (-4.28 mmHg, p = 033). Further studies are required to replicate the potential association of LGALS2 3279 C/T with DBP, and examine whether this SNP could be used as a marker of increased risk for future cardiovascular events in RA populations.
20202925 How to avoid phenotypic misclassification in using joint destruction as an outcome measure 2010 Aug Joint destruction is a measure for RA severity that is accurate, sensitive and reflective of the cumulative disease burden. Risk factors for this outcome measure may be used to arrive at individualized treatment strategies. Currently, relatively few risk factors for joint destruction are known. New risk factors, genetic risk factors in particular, may have relatively small effects on the rate of joint destruction. A sensitive determination of joint damage is then crucial in order to identify these risk factors and will reduce the risk on type 2 errors. The present article addresses the question how the rate of joint destruction is ideally measured. Different methods are discussed and suggestions for corrections of factors that affect the natural course of joint destruction, such as applied treatment strategies, are made. It is concluded that a precise estimation of the rate of radiological joint destruction is obtained by using quantitative and validated scoring methods as well as repetitive measurements over time in order to reduce within patient variation.
20398017 Low-dose glucocorticoid therapy in rheumatoid arthritis: an obligatory therapy. 2010 Apr Glucocorticoids (GCs) are used extensively in patients with rheumatoid arthritis (RA). Recent data on the efficacy of these drugs in alleviating symptoms of inflammation, but also in retarding erosive damage, are presented. In addition, a critical review of the rather limited literature on adverse effects of chronic use of low dose GCs is given. It becomes clear that the net effect of low-dose GCs in the treatment of rheumatoid arthritis favors the beneficial aspects of these drugs above the negative aspects. Prudent use of GCs can be recommended.
20379839 Precore mutant hepatitis B virus-associated fulminant hepatitis during infliximab therapy 2013 Mar A 73-year-old female, who suffered from rheumatoid arthritis for 10 years, developed precore mutant hepatitis B virus-associated fulminant hepatitis after 1 year of infliximab therapy and subsequent methotrexate withdrawal. We emphasize the importance of preemptive antiviral therapy before starting infliximab administration and withdrawing immunosuppressive drugs.
19286846 Anti-cyclic citrullinated peptide antibodies distinguish hepatitis B virus (HBV)-associate 2009 Apr OBJECTIVE: To determine whether anti-cyclic citrullinated peptide (anti-CCP) antibodies, which are a highly specific test for rheumatoid arthritis (RA), could differentiate between hepatitis B virus (HBV)-associated arthropathy and concomitant RA in Korean patients with chronic HBV infection. METHODS: We investigated 240 patients with HBV infection. Anti-CCP antibodies were measured by ELISA and rheumatoid factor (RF) by the latex fixation test. Patient records were reviewed, and a standard form was used to record all demographic, clinical, and laboratory characteristics. Patients were divided into 4 groups according to joint symptoms: asymptomatic, arthralgia, oligoarthritis, and RA. We categorized liver disease into 3 groups: carrier, chronic hepatitis, and cirrhosis. RESULTS: Anti-CCP antibodies and RF were detected in 11 and 28 of 240 patients, respectively. Anti-CCP antibodies were detected in 9 of 10 RA (90%) and 2 of 230 non-RA patients (0.86%). The positive rate for RF was 90% in RA and 8.3% in non-RA. Eight of 10 RA patients were positive for both RF and anti-CCP antibodies. RF was detected in 11 patients without joint symptoms, 4 with arthralgia, and 4 with oligoarthritis, whereas anti-CCP antibodies were found in 1 patient without joint symptoms and 1 with oligoarthritis. Specificity of anti-CCP antibody for RA was 99.1%, whereas RF showed 91.7% specificity (p<0.0002). We compared the titers and positive detection rates of anti-CCP antibodies and RF among liver disease subgroups. There was no significant between-subgroup difference. CONCLUSION: Measurement of anti-CCP antibodies is better than RF detection to discriminate HBV-associated arthropathy from concomitant RA in patients with chronic HBV infection.
19443596 Inflammatory cytokines and hypoxia contribute to 18F-FDG uptake by cells involved in pannu 2009 Jun Assessment of the activity of rheumatoid arthritis (RA) is important for the prediction of future articular destruction. (18)F-FDG PET is known to represent the metabolic activity of inflammatory disease, which correlates with the pannus volume measured by MRI or ultrasonography. To evaluate the correlation between (18)F-FDG accumulation and RA pathology, we assessed (18)F-FDG accumulation in vivo using collagen-induced arthritis (CIA) animal models and (3)H-FDG uptake in vitro using various cells involved in arthritis. METHODS: (18)F-FDG PET images of rats with CIA were acquired on days 10, 14, and 17 after arthritis induction. The specimens were subsequently subjected to macroautoradiography, and the (18)F-FDG accumulation was compared with the histologic findings. (3)H-FDG uptake in vitro in inflammatory cells (neutrophils, macrophages, T cells, and fibroblasts) was measured to evaluate the contributions of these cells to (18)F-FDG accumulation. In addition, the influence on (3)H-FDG uptake of inflammatory factors, such as cytokines (tumor necrosis factor alpha [TNFalpha], interleukin 1 [IL-1], and IL-6), and hypoxia was examined. RESULTS: (18)F-FDG PET depicted swollen joints, and (18)F-FDG accumulation increased with the progression of arthritis. Histologically, a higher level of (18)F-FDG accumulation correlated with the pannus rather than the infiltration of inflammatory cells around the joints. In the in vitro (3)H-FDG uptake assay, fibroblasts showed the highest (3)H-FDG uptake, followed by neutrophils. Although only a small amount of (3)H-FDG was incorporated by resting macrophages, a dramatic increase in (3)H-FDG uptake in both fibroblasts and macrophages was observed when these cells were exposed to inflammatory cytokines, such as TNFalpha and IL-1, and hypoxia. Although neutrophils showed relatively high (3)H-FDG uptake without activation, no increase in (3)H-FDG uptake was observed in response to inflammatory cytokines. (3)H-FDG uptake by T cells was much lower than that by other cells. Thus, fibroblasts and activated macrophages contribute to a high level of (18)F-FDG accumulation in the pannus, and hypoxia as well as cytokine stimulation significantly increases (18)F-FDG uptake by these cells. CONCLUSION: (18)F-FDG accumulation in RA reflects proliferating pannus and inflammatory activity enhanced by inflammatory cytokines and hypoxia. (18)F-FDG PET should be effective for quantifying the inflammatory activity of RA.
20423481 Lack of replication of genetic predictors for the rheumatoid arthritis response to anti-TN 2010 INTRODUCTION: We aimed to replicate the strong associations that a recent genome wide association study (GWAS) has found between 16 single nucleotide polymorphisms (SNPs) and response to anti-tumour necrosis factor (TNF) treatment in 89 patients with rheumatoid arthritis (RA). This study is very important because, according to published simulations, associations as strong as the reported ones will mean that these SNPs could be used as predictors of response at the individual level. METHODS: Disease activity score (DAS28) was evaluated in 151 anti-TNF treated patients with RA of Spanish ancestry at baseline and every 3 months thereafter. Genotypes of the 16 putative predictor SNPs were obtained by single-base extension. Association between the relative change in DAS28 and SNP genotypes was tested by linear regression. In addition, logistic regression was applied to compare genotypes in non-responders (n = 34) versus good-responders (n = 61) following the EULAR response criteria. RESULTS: None of the analyses showed any significant association between the 16 SNPs and response to anti-TNF treatments at 3 or 6 months. Results were also negative when only patients treated with infliximab (66.9% of the total) were separately analyzed. These negative results were obtained in spite of a very good statistical power to replicate the reported strong associations. CONCLUSIONS: We still do not have any sound evidence of genetic variants associated with RA response to anti-TNF treatments. In addition, the possibility we had envisaged of using the results of a recent GWAS for prediction in individual patients should be dismissed.
20510239 A multitude of kinases--which are the best targets in treating rheumatoid arthritis? 2010 May Small-molecule kinase inhibitors are increasingly taking center stage in the quest for new drugs for the treatment of rheumatoid arthritis (RA). By targeting kinases, small-molecule inhibitors can exert potent anti-inflammatory and immunomodulatory effects; the success of small-molecule kinase inhibitors in the treatment of cancer has spurred efforts to identify kinases that could be targeted for the treatment of chronic inflammatory disorders, such as RA. Although many kinase inhibitors have proved efficacious in the treatment of inflammatory arthritis in animals few have been tested in RA clinical trials. This article discusses the challenges and progress in the pursuit of small-molecule kinase inhibitors for RA, including lessons learned from the failure of erstwhile frontrunner inhibitors and the promise of inhibitors making their debut on the RA stage.
21113712 Anti-cyclic citrullinated peptide antibody predicts functional disability in patients with 2012 Feb To clarify the clinical significance of anti-cyclic citrullinated peptide antibody (anti-CCP) in the long-term outcome of RA, we established a large observational cohort of RA patients (IORRA) in our institute beginning in 2000. Essentially all RA patients who consulted our institute were registered, and clinical parameters, including disease activity and drug use, were assessed biannually based on patient reports, physician examinations, and laboratory data. In the third phase (October 2001) of the IORRA survey, anti-CCP levels were measured in 1,226 RA patients. In a cross-sectional analysis, clinical variables were compared in anti-CCP-positive versus -negative patients and in RF-positive versus -negative patients. In a longitudinal analysis, subsequent progression of disability was analyzed in anti-CCP-positive versus -negative and in RF-positive versus -negative patients. A verified Japanese version of the Health Assessment Questionnaire (J-HAQ) was used to measure functional disability. In the cross-sectional analysis, anti-CCP-positive patients (84.2%) had a significantly longer disease duration and higher disease activity score and more frequently used corticosteroids and methotrexate compared to anti-CCP-negative patients statistically. Similar phenomena were noted between RF-positive and -negative patients. In contrast, the longitudinal analysis revealed that J-HAQ slopes-a measure of progression of functional disability-were strongly associated with anti-CCP positivity but not with RF positivity. In a linear regression model, J-HAQ scores significantly worsened in anti-CCP-positive patients compared to anti-CCP-negative patients at the third year (annual progression 0.0317, P = 0.001) and the fifth year (annual progression 0.0199, P = 0.0012); however, J-HAQ progression was not influenced by RF status. Anti-CCP is a better predictive and discriminative marker for progression of disability in the long-term outcome of RA patients compared to RF.
19342676 Heat shock protein 96 is elevated in rheumatoid arthritis and activates macrophages primar 2009 Apr 15 Macrophages are important mediators of chronic inflammation and are prominent in the synovial lining and sublining of patients with rheumatoid arthritis (RA). Recently, we demonstrated increased TLR2 and TLR4 expression and increased response to microbial TLR2 and TLR4 ligands in macrophages from the joints of RA. The current study characterized the expression of the 96-kDa heat shock glycoprotein (gp96) in the joints of RA and its role as an endogenous TLR ligand to promote innate immunity in RA. gp96 was increased in RA compared with osteoarthritis and arthritis-free control synovial tissues. The expression of gp96 strongly correlated with inflammation and synovial lining thickness. gp96 was increased in synovial fluid from the joints of RA compared with disease controls. Recombinant gp96 was a potent activator of macrophages and the activation was mediated primarily through TLR2 signaling. The cellular response to gp96 was significantly stronger with RA synovial macrophages compared with peripheral blood monocytes from RA or healthy controls. The transcription of TLR2, TNF-alpha, and IL-8, but not TLR4, was significantly induced by gp96, and the induction was significantly greater in purified RA synovial macrophages. The expression of TLR2, but not TLR4, on synovial fluid macrophages strongly correlated with the level of gp96 in the synovial fluid. The present study documents the potential role of gp96 as an endogenous TLR2 ligand in RA and provides insight into the mechanism by which gp96 promotes the chronic inflammation of RA, identifying gp96 as a potential new therapeutic target.
19191904 Differential gene expression of peripheral blood mononuclear cells from rheumatoid arthrit 2009 Jul This study aimed to evaluate the association between the differential gene expression profiling of peripheral blood mononuclear cells of rheumatoid arthritis patients with their immunogenetic (human leucocyte antigen shared-epitope, HLA-SE), autoimmune response [anti-cyclic citrullinated peptide (CCP) antibodies], disease activity score (DAS-28) and treatment (disease-modifying antirheumatic drugs and tumour necrosis factor blocker) features. Total RNA samples were copied into Cy3-labelled complementary DNA probes, hybridized onto a glass slide microarray containing 4500 human IMAGE complementary DNA target sequences. The Cy3-monocolour microarray images from patients were quantified and normalized. Analysis of the data using the significance analysis of microarrays algorithm together with a Venn diagram allowed the identification of shared and of exclusively modulated genes, according to patient features. Thirteen genes were exclusively associated with the presence of HLA-SE alleles, whose major biological function was related to signal transduction, phosphorylation and apoptosis. Ninety-one genes were associated with disease activity, being involved in signal transduction, apoptosis, response to stress and DNA damage. One hundred and one genes were associated with the presence of anti-CCP antibodies, being involved in signal transduction, cell proliferation and apoptosis. Twenty-eight genes were associated with tumour necrosis factor blocker treatment, being involved in intracellular signalling cascade, phosphorylation and protein transport. Some of these genes had been previously associated with rheumatoid arthritis pathogenesis, whereas others were unveiled for future research.
19144159 Women, men, and rheumatoid arthritis: analyses of disease activity, disease characteristic 2009 INTRODUCTION: Gender as a predictor of outcomes of rheumatoid arthritis (RA) has evoked considerable interest over the decades. Historically, there is no consensus whether RA is worse in females or males. Recent reports suggest that females are less likely than males to achieve remission. Therefore, we aimed to study possible associations of gender and disease activity, disease characteristics, and treatments of RA in a large multinational cross-sectional cohort of patients with RA called Quantitative Standard Monitoring of Patients with RA (QUEST-RA). METHODS: The cohort includes clinical and questionnaire data from patients who were seen in usual care, including 6,004 patients at 70 sites in 25 countries as of April 2008. Gender differences were analyzed for American College of Rheumatology Core Data Set measures of disease activity, DAS28 (disease activity score using 28 joint counts), fatigue, the presence of rheumatoid factor, nodules and erosions, and the current use of prednisone, methotrexate, and biologic agents. RESULTS: Women had poorer scores than men in all Core Data Set measures. The mean values for females and males were swollen joint count-28 (SJC28) of 4.5 versus 3.8, tender joint count-28 of 6.9 versus 5.4, erythrocyte sedimentation rate of 30 versus 26, Health Assessment Questionnaire of 1.1 versus 0.8, visual analog scales for physician global estimate of 3.0 versus 2.5, pain of 4.3 versus 3.6, patient global status of 4.2 versus 3.7, DAS28 of 4.3 versus 3.8, and fatigue of 4.6 versus 3.7 (P < 0.001). However, effect sizes were small-medium and smallest (0.13) for SJC28. Among patients who had no or minimal disease activity (0 to 1) on SJC28, women had statistically significantly higher mean values compared with men in all other disease activity measures (P < 0.001) and met DAS28 remission less often than men. Rheumatoid factor was equally prevalent among genders. Men had nodules more often than women. Women had erosions more often than men, but the statistical significance was marginal. Similar proportions of females and males were taking different therapies. CONCLUSIONS: In this large multinational cohort, RA disease activity measures appear to be worse in women than in men. However, most of the gender differences in RA disease activity may originate from the measures of disease activity rather than from RA disease activity itself.
20560456 [Anti-cyclic citrullinated peptide antibodies and rheumatoid arthritis]. 2010 May Rheumatoid arthritis (RA) is a severe, progressive, systemic inflammatory disease of unknown etiology. Early diagnosis of RA is important to identify individuals who will develop severe destructive disease, so that effective treatment can be initiated before irreversible damage occurs. Rheumatoid factor (RF) has been commonly used as a serological marker for RA, although RF had a tolerable sensitivity of 75.9% for RA, but low specificity of 78.7% and 75.4% for patients with other rheumatic diseases and chronic inflammatory disease, respectively. Antibodies to citrullinated protein/peptide antigens, i.e., to peptides post-translationally modified by the conversion of arginine to cilrulline (ACPA), are specific serological markers for RA. Not only did anti-cyclic citrullinated peptide antibody (anti-CCP) demonstrate a higher sensitivity of 78.5% when compared to RF, but anti-CCP also had a much higher specificity of 95.9% and 97.9% for other rheumatic diseases and chronic inflammatory disease patients, respectively. Moreover, meta-analysis revealed that pooled sensitivity and pooled specificity were 67% and 95% for anti-CCP, 69% and 85% for RF, respectively, and that anti-CCP was more specific than RF for diagnosing RA. In 2009, ACPA (anti-CCP) was included in the new Criteria for RA from the American College of Rheumatology and the European League Against Rheumatism. Anti-CCP testing is particularly useful in the diagnosis of RA, being present early in the disease process, and able to predict severe disease and irreversible damage. In addition, the titers might be early predictors of the efficacy of anti-TNF therapy. In this review, we discuss the historical background of anti-CCP as well as its diagnostic performance, usefulness for early diagnosis, prognostic capability, and pathogenesis of RA.
19333979 Association between anti-cyclic citrullinated peptide antibodies and ischemic heart diseas 2009 Apr 15 OBJECTIVE: Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular disease that may not always be related to the presence of traditional cardiovascular risk factors. The aim of this study was to determine if anti-cyclic citrullinated peptide (anti-CCP) antibodies are associated with cardiovascular disease in patients with RA. METHODS: Anti-CCP antibodies were determined by enzyme-linked immunosorbent assay in the earliest serum sample available from 937 patients with a diagnosis of RA. We studied the relationship between anti-CCP antibodies with traditional cardiovascular risk factors and cardiovascular events. RESULTS: We found positive anti-CCP antibodies (>25 units/ml) in 672 patients (71.7%). There was no association between the anti-CCP antibodies and cardiovascular risk factors such as smoking, hypertension, dyslipidemia, being overweight, or diabetes mellitus. However, patients who had positive anti-CCP antibodies experienced more frequent ischemic heart disease (6.5% versus 2.6%; odds ratio [OR] 2.58, 95% confidence interval [95% CI] 1.17-5.65) and had higher mortality rates (11.2% versus 6.8%; OR 1.72, 95% CI 1.01-2.91). Similar results were obtained when we considered anti-CCP titers 20-fold higher (>500 units/ml). Multivariable analysis showed that ischemic heart disease is independently associated with positive anti-CCP antibodies (OR 2.8, 95% CI 1.19-6.56; P = 0.009). CONCLUSION: Anti-CCP antibodies in patients with RA are independently associated with the development of ischemic heart disease.
19483227 The Medial Rotation total knee replacement: a clinical and radiological review at a mean f 2009 Jun We describe the survivorship of the Medial Rotation total knee replacement (TKR) at ten years in 228 cemented primary replacements implanted between October 1994 and October 2006, with their clinical and radiological outcome. This implant has a highly congruent medial compartment, with the femoral component represented by a portion of a sphere which articulates with a matched concave surface on the medial side of the tibial insert. There were 78 men (17 bilateral TKRs) and 111 women (22 bilateral TKRs) with a mean age of 67.9 years (28 to 90). All the patients were assessed clinically and radiologically using the American Knee Society scoring systems. The mean follow-up was for six years (1 to 13) with only two patients lost to follow-up and 34 dying during the period of study, one of whom had required revision for infection. There were 11 revisions performed in total, three for aseptic loosening, six for infection, one for a periprosthetic fracture and one for a painful but well-fixed replacement performed at another centre. With revision for any cause as the endpoint, the survival at ten years was 94.5% (95% CI 85.1 to 100), and with aseptic loosening as the endpoint 98.4% (95% CI 93 to 100). The mean American Knee Society score improved from 47.6 (0 to 88) to 72.2 (26 to 100) and for function from 45.1 (0 to 100) to 93.1 (45 to 100). Radiological review failed to detect migration in any of the surviving knees. The clinical and radiological results of the Medial Rotation TKR are satisfactory at ten years. The increased congruence of the medial compartment has not led to an increased rate of loosening and continued use can be supported.
19604442 Decreased RAGE expression in peripheral blood mononuclear cells of patients with rheumatoi 2009 May OBJECTIVE: Interactions between the multiligand receptor for advanced glycation end products (RAGE) and its proinflammatory ligands (AGEs, S100/calgranulins, HMBG1, Mac-1) may contribute to inflammatory responses playing a key role in the pathogenesis of chronic inflammatory diseases such as in rheumatoid arthritis (RA). Peripheral blood mononuclear cells (PBMCs) participate in the development of chronic inflammatory diseases. This study investigated expression of the RAGE variants endogenous secretory RAGE (esRAGE), N-truncated RAGE (NtRAGE) and complete RAGE (cRAGE: encoding full-length RAGE, esRAGE and NtRAGE) in PBMCs of patients with RA in comparison to healthy control subjects (controls) and to patients with Crohn's disease (CD) as another chronic inflammatory disease. METHODS: The cRAGE, esRAGE and NtRAGE mRNA expression levels of PBMCs from controls, RA and CD patients were measured by real-time PCR. The RAGE protein expression was determined by Western blot analysis and the esRAGE plasma levels by ELISA. RESULTS: PBMCs of RA patients showed significantly decreased mRNA expression for cRAGE (46%), esRAGE (54.0%) and NtRAGE (52%) in comparison to healthy controls (100%). For CD patients, also a down-regulation but to a lower extent was found (cRAGE: 79%; esRAGE: 76%; NtRAGE: 69%). Related to controls, RA PBMCs showed a significantly reduced protein expression of full-length RAGE (53%) as well as significantly decreased esRAGE plasma concentrations (70%). CONCLUSION: The down-regulation of RAGE isoforms in RA PBMCs may contribute to reduced intracellular responses mediated by the cell-standing receptor as well as to a lowered capability of trapping inflammatory ligands by circulating esRAGE.
18830905 Changes in disease activity, cytokine production, and proliferation of peripheral blood mo 2009 Jan OBJECTIVES: The aim of this study was to investigate changes in disease activity, cytokine profiles, and proliferation of peripheral blood mononuclear cells (PBMCs) in active rheumatoid arthritis (RA) patients treated with simvastatin. METHODS: Thirty-three patients with active RA were prescribed simvastatin (40 mg/day) for 3 months. Most of the patients received background traditional disease-modifying anti-rheumatic drugs (DMARDs) in stable doses. At the end of treatment there was a reduction in the 28-joint Disease Activity Score (DAS28) and in the Health Assessment Questionnaire (HAQ) score. RESULTS: Eleven patients (33%) achieved a moderate European League Against Rheumatism (EULAR) response. There was a decrease in circulating interleukin (IL)-17 concentrations and spontaneous PBMC proliferation. Anti-CD3-stimulated IL-10 and tumour necrosis factor (TNF)alpha production by PBMCs was upregulated after simvastatin therapy. A reduction in serum IL-6 was detected only in the responder group. Baseline circulating IL-10 concentrations were higher in responders than in non-responders. CONCLUSION: Simvastatin treatment is associated with moderate clinical improvement in patients with active RA. Immunological changes produced by simvastatin in peripheral blood are complex and may reflect both its anti- and pro-inflammatory properties.
18663553 The changes in serum chemokines following leflunomide therapy in patients with rheumatoid 2009 Jan We undertook this study to evaluate the effects of leflunomide, an oral pyrimidine synthesis inhibitor, on the serum chemokine levels in patients with active rheumatoid arthritis (RA) who were refractory to treatment with methotrexate (MTX) or did not tolerated MTX treatment. RA patients were supposed to receive leflunomide (100 mg/day loading dose for 3 days followed by 20 mg/day orally for the 12 months). Serum concentrations of RANTES (regulated upon activation, normal T cell expressed and secreted), monocyte chemoattractant protein-1 (MCP-1), and interleukin-8 (IL-8) were assessed by enzyme-linked immunosorbent assay before and after 3, 6, 9, and 12 months of treatment with leflunomide. Three months therapy with leflunomide caused reduction in serum RANTES and MCP-1 (in both cases, p < 0.001) levels. Decrease in the concentration of these chemokines persisted until the end of the study period but was less significant. In the case of IL-8, its serum levels significantly diminished after 6 months of therapy with leflunomide (p < 0.01) and remained stable to the end of the study. Changes in serum chemokine levels were accompanied by significant decrease of disease activity score (DAS; p < 0.001). Prior to the first dose of leflunomide, serum concentrations of studied chemokines correlated with marker of RA activity such as the erythrocyte sedimentation rate and IL-8 level with DAS. Furthermore, we demonstrated significant correlations between serum levels of RANTES, MCP-1, and IL-8. During study period, such associations were far less or not significant. Leflunomide, beside a clinical improvement, reduce serum chemokines concentrations in RA patients. Leflunomide seems to be an effective treatment for RA, alternative to current therapies.
19176545 Comparison of interferon {gamma} release assays and conventional screening tests before tu 2010 Jan OBJECTIVE: To compare the performance of two interferon gamma release assays (IGRAs) and conventional screening tests in patients with inflammatory arthritis undergoing screening for latent tuberculosis infection (LTBI) before treatment with anti-tumour necrosis factor alpha (anti-TNFalpha) compounds. METHODS: Successive patients were subjected to conventional LTBI screening, including a tuberculin skin test (TST). The T-SPOT.TB test was performed on all patients and the QuantiFERON-TB Gold test was performed on a large subset. The results of the IGRAs were compared with the results of conventional screening tests. RESULTS: A total 150 patients were evaluated. The majority (57.9%) had rheumatoid arthritis. Previous vaccination with Bacille Calmette-Guerin was confirmed in 82% of patients. No patient had received prior anti-TB treatment. A total of 57 patients (38.0%) had at least one positive conventional risk factor. In contrast, an unequivocally positive T-SPOT.TB test was seen in only 14/143 (9.8%). There was 98.2% agreement between the two IGRAs. Statistically significant associations were found between each of the IGRAs and both TST and risk history, but not chest x-ray (CXR). A positive IGRA result was significantly associated with increased age. TB was not reactivated in any patient during the follow-up period. INTERPRETATION: This study suggests that IGRAs may be useful when screening for LTBI before anti-TNFalpha therapy in patients with immune-mediated inflammatory diseases. The observations reported here also highlight the inadequate performance of CXR as a marker of LTBI.
20643765 Ability of ultrasound imaging to detect erosions in a bone phantom model. 2010 Sep OBJECTIVES: The authors examined the validity, interobserver reliability and interscanner variation in detecting bone erosions with ultrasonography using a custom-made phantom. METHODS: 21 bovine bones were used. Artificial erosions were made into 15 bones and six bones were left as controls. In the processed bones the numbers of erosions, their depths and widths varied between 1-7, 1-4 and 1.5-5 mm, respectively. Each bone was coated with polyvinyl alcohol cryogel to mimic overlying soft tissue and to hide the erosions. Four musculoskeletal sonography experts scanned the 21 blind-coded phantoms using one of the three sets of ultrasound equipment. Finally, quality assurance measurements of the ultrasound equipment was carried out using two additional bone samples. RESULTS: The sonographers detected the erosions successfully with ultrasound. The mean correlation coefficient for a correct result in terms of the number of erosions detected was 0.88 (range 0.75-0.975). The overall Cohen's kappa coefficient for interobserver agreement was 0.683 in terms of discrimination between healthy bones and bones with erosions. The different sets of equipment showed that their overall performance was equal. CONCLUSIONS: The sonographers had good correlations with the number of erosions and they were successful in separating healthy bones from bones with erosions. It seems that neither depth nor width is crucial but that in experimental conditions a 1.5 mm erosion width was the limit for the resolution with current ultrasound equipment. Ultrasound is a valid and reliable method of detecting cortical bone erosions in vitro, when the round erosion is at least 1 mm deep and 1.5 mm wide.