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ID PMID Title PublicationDate abstract
18075741 The imbalance between osteoprotegerin and cathepsin K in the serum of patients with longst 2008 May Osteoprotegerin (OPG) and soluble receptor activator of NF-kappa B ligand (sRANKL) together regulate the bone metabolism among other cytokines, whereby cathepsin K has a potent collagen-degrading activity. An imbalance of this system may be partly responsible for the skeletal complications of RA. Expanding on a previous study, we investigated the relationship between OPG, sRANKL and cathepsin K levels in the serum of patients with longstanding RA. We measured serum levels of OPG, sRANKL and cathepsin K of 100 patients with active, longstanding RA. We detected elevated serum levels of cathepsin K (median 54.8 pmol/l) and OPG (median 4.8 pmol/l), but normal sRANKL levels (median 0.2 pmol/l). Cathepsin K did not show a correlation with the overexpressed OPG (P=0.64) and sRANKL (P=0.81). The radiological destruction correlates significantly with cathepsin K (P=0.004) and OPG (P=0.007). We speculate that the increased levels of OPG are effective in compensating the action of sRANKL, but do not directly prevent bone degradation, as reflected by the elevated serum levels of cathepsin K.
17964793 Profiling Protein Arginine Deiminase 4 (PAD4): a novel screen to identify PAD4 inhibitors. 2008 Jan 15 Protein Arginine Deiminase 4 (PAD4) has emerged as a leading target for the development of a Rheumatoid Arthritis (RA) pharmaceutical. Herein, we describe the development of a novel screen for PAD4 inhibitors that is based on a PAD4-targeted Activity-Based Protein Profiling reagent, denoted Rhodamine-conjugated F-Amidine (RFA). This screen was validated by screening 10 Disease Modifying Anti-Rheumatic Drugs (DMARDs) and identified streptomycin, minocycline, and chlortetracycline as micromolar inhibitors of PAD4 activity.
19034456 Protein tyrosine phosphatase gene C1858T allele confers risk for rheumatoid arthritis in H 2009 May The C1858T allele of the PTPN22 gene has been reported to confer risk for RA; but in some reports, the effect was restricted to RF- and/or anti-CCP-seropositive patients. Hungarian RA patients and matched controls were genotyped. The 1858T allele showed an increased prevalence in RA patients compared to controls. The 1858T allele represents a risk factor in the whole RA population (P = 0.001); an association was found both in RF-seropositive (P = 0.001) and anti-CCP-seropositive patients (P = 0.001), and in subjects with the combination of these factors (P = 0.002). In TT homozygotes, the estimated susceptibility to RA was more than double (OR = 5.04) of that seen in TC heterozygotes (OR = 1.89); the same gene dosage effect was observed in all seropositive RA subgroups. Our data show that the Hungarian RA patients belong to the populations in which the 1858T allele represents a susceptibility factor both in the RF- and/or anti-CCP-seropositive subjects, and the association exhibit a gene dosage dependency.
17055300 Arthroscopic rotator cuff debridement in patients with rheumatoid arthritis. 2007 Jan There is little information available concerning the results of rotator cuff debridement in patients with rheumatoid arthritis (RA). We performed a review of 16 shoulders with underlying RA that underwent arthroscopic rotator cuff tear debridement; there were 10 full-thickness tears and 6 partial-thickness tears. Of the 10 patients with full-thickness rotator cuff tears, 8 had unsatisfactory results, whereas none of the patients with partial-thickness tears had unsatisfactory results. Pain was improved in 5 of 6 shoulders with partial-thickness cuff tears, whereas only 5 of 10 with full-thickness tears had an improvement with regard to pain. Motion did not improve in either group. Patients with RA who require operative intervention for pain relief because of rotator cuff tearing can be treated successfully with debridement alone. However, pain relief was less predictable with large or massive tears when compared with partial-thickness tears, and functional gains were not achieved in either group.
16691045 [The effect of Tai Chi movement in patients with rheumatoid arthritis]. 2006 Apr PURPOSE: This study was performed to verify the effect of Tai Chi exercise on patients with rheumatoid arthritis particularly their level of pain, fatigue, sense of balance and daily life performance (ADL). METHOD: It employed a non-equivalent control group pre- and post-test design. The research instruments used in this study were pain, fatigue, sense of balance and ADL. Thirty-two patients in the experimental group carried out 50 minutes of Tai Chi exercise for 12 weeks, and 29 patients in the control group did not. Before and after the experiment, both groups were tested for pain, fatigue, sense of balance and ADL. Collected data were processed using the SPSS/WIN 10.0 program analyzed by the frequency, percentage, chi2-test, and t-test. RESULTS: Pain and fatigue significantly decreased in the experimental group. However the improvement in ADL of the rheumatoid arthritis patients was not statistically significant but their sense of balance was enhanced significantly. CONCLUSION: Tai Chi exercise is an effective nursing intervention that can be used for rheumatoid arthritis patients.
19052348 The role of reactive oxygen species in immunopathogenesis of rheumatoid arthritis. 2008 Dec Rheumatoid arthritis is a disease associated with painful joints that affects approximately 1% of the population worldwide, and for which no effective cure is available. It is characterized by chronic joint inflammation and variable degrees of bone and cartilage erosion. Oxygen metabolism has an important role in the pathogenesis of rheumatoid arthritis. Reactive oxygen species (ROS) are produced in many normal and abnormal processes in humans, including atheroma, asthma, joint diseases, aging, and cancer. TNF-alpha overproduction is thought to be the main contributor to increased ROS release in patients with RA. Increased ROS production leads to tissue damage associated with inflammation. The prevailing hypothesis that ROS promote inflammation was recently challenged when polymorphisms in Neutrophil cytosolic factor 1(Ncf1), that decrease oxidative burst, were shown to increase disease severity in mouse and rat arthritis models. It has been shown that oxygen radicals might also be important in controlling disease severity and reducing joint inflammation and connective tissue damage. In this review article, our aim is to clarify the role of ROS in immunopathogenesis of Rheumatoid arthritis.
18163412 Physical inactivity in patients with rheumatoid arthritis: data from twenty-one countries 2008 Jan 15 OBJECTIVE: Regular physical activity is associated with decreased morbidity and mortality. Traditionally, patients with rheumatoid arthritis (RA) have been advised to limit physical exercise. We studied the prevalence of physical activity and associations with demographic and disease-related variables in patients with RA from 21 countries. METHODS: The Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST-RA) is a cross-sectional study that includes a self-report questionnaire and clinical assessment of nonselected consecutive outpatients with RA who are receiving usual clinical care. Frequency of physical exercise (>or=30 minutes with at least some shortness of breath, sweating) is queried with 4 response options: >or=3 times weekly, 1-2 times weekly, 1-2 times monthly, and no exercise. RESULTS: Between January 2005 and April 2007, a total of 5,235 patients from 58 sites in 21 countries were enrolled in QUEST-RA: 79% were women, >90% were white, mean age was 57 years, and mean disease duration was 11.6 years. Only 13.8% of all patients reported physical exercise>or=3 times weekly. The majority of the patients were physically inactive with no regular weekly exercise: >80% in 7 countries, 60-80% in 12 countries, and 45% and 29% in 2 countries, respectively. Physical inactivity was associated with female sex, older age, lower education, obesity, comorbidity, low functional capacity, and higher levels of disease activity, pain, and fatigue. CONCLUSION: In many countries, a low proportion of patients with RA exercise. These data may alert rheumatologists to motivate their patients to increase physical activity levels.
18602896 The A3 adenosine receptor agonist CF502 inhibits the PI3K, PKB/Akt and NF-kappaB signaling 2008 Aug 15 The A(3) adenosine receptor (A(3)AR) is over-expressed in inflammatory cells and was defined as a target to combat inflammation. Synthetic agonists to this receptor, such as IB-MECA and Cl-IB-MECA, exert an anti-inflammatory effect in experimental animal models of adjuvant- and collagen-induced arthritis. In this study we present a novel A(3)AR agonist, CF502, with high affinity and selectivity at the human A(3)AR. CF502 induced a dose dependent inhibitory effect on the proliferation of fibroblast-like synoviocytes (FLS) via de-regulation of the nuclear factor-kappa B (NF-kappaB) signaling pathway. Furthermore, CF502 markedly suppressed the clinical and pathological manifestations of adjuvant-induced arthritis (AIA) in a rat experimental model when given orally at a low dose (100 microg/kg). As is typical of other G-protein coupled receptors, the A(3)AR expression level was down-regulated shortly after treatment with agonist CF502 in paw and in peripheral blood mononuclear cells (PBMCs) derived from treated AIA animals. Subsequently, a decrease in the expression levels of protein kinase B/Akt (PKB/Akt), IkappaB kinase (IKK), I kappa B (IkappaB), NF-kappaB and tumor necrosis factor-alpha (TNF-alpha) took place. In addition, the expression levels of glycogen synthase kinase-3 beta (GSK-3beta), beta-catenin, and poly(ADP-ribose)polymerase (PARP), known to control the level and activity of NF-kappaB, were down-regulated upon treatment with CF502. Taken together, CF502 inhibits FLS growth and the inflammatory manifestations of arthritis, supporting the development of A(3)AR agonists for the treatment of rheumatoid arthritis.
16639489 [Case report: RAEB in a patient with rheumatoid arthritis treated with methotrexate and in 2006 Jan Anti TNF-alpha drugs seem to be the new frontier of Rheumatoid Arthritis (RA) therapy. The association infliximab methotrexate has been approved for the treatment of RA not responding to the classic therapy, but the short clinical experience in using antiTNF-alpha molecules brings to segnalation of new risks or adverse events. We describe a case of a patient, treated for many years with classic RA therapy, which developed a refractory anemia after treatment with association infliximab-methotrexate.
22320032 [Usefulness of examinations of serum levels of matrix metalloproteinases 1, MMP-3, MMP-9, 2008 Lyme disease is a multisystem disease that can affect skin, nervous system, heart and joints. Lyme arthritis can develope in about 60% of "not treated" Lyme disease patients, 10% of patients may develope chronic arthritis. Lyme arhritis symptoms (especially chronic arthritis) is similar to rheumatoid arthritis. The purpose of this study was to establish the usefulness of examinations of serum levels of matrix metalloproteinases MMP-3, MMP-9, tissue inhibitor of metalloproteinases 1 (TIMP-1), hialuronic acid (HA) and antibodies against cyclic citrullinated peptide (anti-CCP) in Lyme arthritis, rheumatoid arthritis (RA) and patients with arthritic complaints. Plasma levels of MMP-3, HA and anti-CCP were significantly higher in RA group than in Lyme arthritis group and patients with arthritic complaints. There were no significant differences in serum levels of MMP-3, MMP-9, TIMP-1, HA, anti-CCP between Lyme arthritis patients and patients with arthritic complaints and these parameters are not usefull in differential diagnoses of Lyme arthritis.
15770483 Soluble CD21 in sera and synovial fluid of arthritic patients. 2006 Jan Soluble CD21 (sCD21) is the ectodomain of the CD21 glycoprotein released by shedding from the cellular membrane. The ectodomain of CD21 is capable of binding complement fragments, Epstein-Barr virus (EBV) and CD23. Functionally sCD21 can activate monocytes and abrogate B-cell/follicular dendritic cell interaction, thereby inhibiting antibody production by antigen primed B cells. Levels of sCD21 vary in several clinical conditions. Here we analyzed sCD21 in synovial fluids and sera in arthritic patients. sCD21 concentrations were consistently lower in synovial fluids compared to paired sera samples from the same patients. In contrast to healthy donors, sCD21 levels are significantly reduced in rheumatoid arthritis patient's sera. Potential causes and consequences of the data are discussed.
16476711 Epistatic interaction between FCRL3 and NFkappaB1 genes in Spanish patients with rheumatoi 2006 Sep BACKGROUND: A Japanese study has described a strong association between rheumatoid arthritis and several polymorphisms located in the Fc receptor-like 3 (FCRL3) gene, a member of a family of genes related to Fc receptors located on chromosome 1q21-23. OBJECTIVES: To evaluate the association between rheumatoid arthritis and FCLR3 polymorphisms in a large cohort of Caucasian patients with rheumatoid arthritis and healthy controls of Spanish origin. Owing to the described functional link between the FCRL3 polymorphisms and the transcription factor nuclear factor kappaB (NFkappaB), a functional polymorphism located in the NFkappaB1 gene was included. METHODS: 734 patients with rheumatoid arthritis from Madrid and Granada, Spain, were included in the study, along with 736 healthy controls. Polymorphisms in the FCRL3 gene were studied by TaqMan technology. The -94ins/delATTG NFkappaB1 promoter polymorphism was analysed by fragment analysis after polymerase chain reaction with labelled primers. Genotypes were compared using 3x2 contingency tables and chi2 values. RESULTS: No overall differences were found in any of the FCRL3 polymorphisms and in the NFkappaB1 promoter polymorphism when patients were compared with controls. However, when stratified according to NFkappaB1 genotypes, a susceptibility effect of FCRL3 polymorphisms was observed in patients who were heterozygotes for NFkappaB1 (pc = 0.003). CONCLUSIONS: The FCRL3 polymorphisms associated with rheumatoid arthritis in a Japanese population are not associated per se with rheumatoid arthritis in a Spanish population. A genetic interaction was found between NFkappaB1 and FCRL3 in Spanish patients with rheumatoid arthritis. These findings may provide a general rationale for divergent genetic association results in different populations.
17765840 Ankle arthrodesis in rheumatoid arthritis: techniques, results, and complications. 2007 Sep This article defines specific risks associated with rheumatoid arthritis, including an increased incidence of medical comorbidities, the use of steroids and other immunosuppressive agents, osteoporosis, vascular disease, and the common occurrence of severe deformity. This article suggests approaches for management and techniques that may improve specific surgical issues in this challenging patient population.
17763428 Reduction in the incidence of myocardial infarction in patients with rheumatoid arthritis 2007 Sep OBJECTIVE: Rheumatoid arthritis (RA) is associated with an increased risk of coronary artery disease, possibly acting via shared mechanisms of inflammation. This study was undertaken to test the hypothesis that the powerful antiinflammatory effect of anti-tumor necrosis alpha (anti-TNFalpha) therapy might lead to a reduction in the incidence of myocardial infarction (MI) in patients with RA. METHODS: Using data from the British Society for Rheumatology Biologics Register, a national prospective observational study, we compared MI rates in 8,670 patients with RA treated with anti-TNFalpha and 2,170 patients with active RA treated with traditional disease-modifying antirheumatic drugs (DMARDs). RESULTS: Through July 2006, 63 MIs occurred in the anti-TNFalpha cohort during 13,233 person-years of followup and 17 MIs occurred in the DMARD cohort during 2,893 person-years of followup, equivalent to a rate of 4.8 events per 1,000 person-years and 5.9 events per 1,000 person-years, respectively. After adjustment for baseline risk factors, there was no reduction in the rate of MI in the anti-TNFalpha cohort compared with the DMARD cohort (incidence rate ratio 1.44 [95% confidence interval 0.56-3.67]). In an analysis of anti-TNFalpha-treated patients who responded to the treatment within 6 months versus those who did not, MI rates were found to be 3.5 events per 1,000 person-years in responders and 9.4 events per 1,000 person-years in nonresponders. The adjusted incidence rate ratio (95% confidence interval) for responders compared with nonresponders was 0.36 (0.19-0.69). CONCLUSION: These results indicate that RA patients treated with anti-TNFalpha do not have a lower incidence of MI compared with RA patients treated with traditional DMARDs. However, the risk of MI is markedly reduced in those who respond to anti-TNFalpha therapy by 6 months compared with nonresponders. This finding supports the notion that inflammation plays a pivotal role in MI.
19074177 Evaluation of different methods used to assess disease activity in rheumatoid arthritis: a 2009 Apr OBJECTIVES: To evaluate different methods of reporting response to treatment or disease status for their ability to discriminate between active therapy and placebo, or to reflect structural progression or patient satisfaction with treatment using an exploratory analysis of the Abatacept in Inadequate Responders to Methotrexate (AIM) trial. METHODS: 424 active (abatacept approximately 10 mg/kg) and 214 placebo-treated patients with rheumatoid arthritis (RA) were evaluated. METHOD: of reporting included: (1) response (American College of Rheumatology (ACR) criteria) versus state (disease activity score in 28 joints (DAS28) criteria); (2) stringency (ACR20 vs 50 vs 70; moderate disease activity state (MDAS; DAS28 <5.1) vs low disease activity state (LDAS; DAS28 or=2). More stringent criteria (at least ACR50/LDAS), faster onset (3 visits) of ACR50/LDAS best reflected patient satisfaction (positive LR >10). CONCLUSIONS: The optimal method for reporting a measure of disease activity may differ depending on the outcome of interest. Time to onset and sustainability can be important factors when evaluating treatment response and disease status in patients with RA.
16805753 Left and right ventricular diastolic functions in patients with rheumatoid arthritis witho 2006 Jun The aim of this study was to assess the prevalence of diastolic dysfunction of the left ventricle (LV) and of the right ventricle in patients with rheumatoid arthritis (RA) without clinically evident cardiovascular manifestations and to estimate whether there is a correlation between the duration of RA and the degree of LV diastolic dysfunction. The study included 81 patients (61 females and 20 males) with RA without clinically evident heart disease (group 1) and 40 healthy subjects (29 females and 11 males) who served as a control group (group 2). Both groups were matched for age and sex. Echocardiographic and Doppler studies were conducted in all patients with RA and control subjects. There were significant differences between patients with RA vs. control group with regard to early diastolic flow velocity (E), atrial flow velocity (A) and the E/A ratio (0.68 +/- 0.19 m/s vs. 0.84 +/- 0.14 m/s, p < 0.001; 0.73 +/- 0.15 m/s vs. 0.66 +/- 0.13 cm/s, p = 0.01; and 0.97 +/- 0.3 vs. 1.32 +/- 0.37, p < 0.001, respectively). There was significant difference between groups regarding the right ventricular early diastolic (Er)/atrial (Ar) flow velocities (Er/Ar ratio) (1.07 +/- 0.3 vs. 1.26 +/- 0.3, p = 0.002). There was a weak correlation between transmitral E/A ratio and the duration of RA (r = - 0.22, p = 0.001). Myocardial performance index (MPI) appeared to differ little in patients with RA as compared with control group (0.51 +/- 0.1 vs. 0.52 +/- 0.2, p = NS). In patients with RA without clinically evident cardiovascular disease, the left ventricular diastolic function and the right ventricular diastolic function are reduced. Left ventricular wall thickness, dimensions, systolic function and MPI were found to be normal. LV diastolic function had a weak correlation with the duration of RA.
16650791 Three-dimensional Doppler sonographic vascular imaging in regions with increased MR enhanc 2006 Oct OBJECTIVE: To compare three-dimensional (3D) power Doppler ultrasonography (PDUS) with contrast enhanced magnetic resonance imaging (MRI) in their capability to visualize synovial vascularity in inflamed wrists of patients with rheumatoid arthritis (RA). METHODS: Nine patients with RA showing clinically active arthritis of the wrist as determined by tenderness and swelling were examined by contrast enhanced MRI and 3D PDUS. Vascularity close to and inside the joint capsule was visualized by conventional power Doppler mode. In a region with high Doppler signal intensity (=region of interest/ROI) a 3D blood vessel tree was obtained by a free-hand sweep. 3D images were evaluated with regard to the number of blood vessels in the intra- and peri-articular region. MRI examinations were performed using a 1.5 T Scanner. In MRI, time resolved coronal contrast enhanced T1-weighted sequences with fat suppression were acquired during an 8 min period to assess tissue enhancement. Relative enhancement was calculated and compared to 3D PDUS findings. RESULTS: A 3D vascular tree consisting of peri- and intra-articular blood vessels could be demonstrated in the same anatomical ROI in which an increased gadolinium enhancement was measured by MRI in all examined RA patients. The number of penetrating vessels into the joint capsule, the number of intra-articular vessels and a semiquantitative estimation of the strength of blood flow were used to generate a 3D score for the intensity of synovial vascularity. CONCLUSION: When compared with clinical symptoms and the gold standard dynamic MRI, 3D PDUS is a reliable imaging technique for assessing synovial vascularity in inflamed wrists of RA patients.
15975964 Efficacy and safety of switching from infliximab to adalimumab: a comparative controlled s 2006 Feb OBJECTIVE: To describe the efficacy and safety of adalimumab in patients with rheumatoid arthritis (RA) who had previously discontinued infliximab treatment. METHODS: 24 patients with RA who discontinued treatment with infliximab (switchers) were treated with adalimumab (40 mg every 2 weeks, subcutaneously) for 12 months. The results were compared with those for 25 patients with RA receiving adalimumab who had not previously used an anti-tumour necrosis factor alpha inhibitor (controls). Disease activity was measured with the 28 joint count Disease Activity Score (DAS28), and clinical response with the American College of Rheumatology (ACR) 20% response criteria. RESULTS: At baseline there were no differences in demographic, clinical, and laboratory features between the two groups. After 12 months' adalimumab treatment, clinical improvement was similar in both groups. More specifically, ACR 20% response criteria were achieved by 18/24 (75%) switchers and by 19/25 (76%) subjects in the control group. Four switchers discontinued the study-two because of adverse events and two because of lack of efficacy, while three control patients discontinued the study-one because of lack of efficacy and two owing to side effects. CONCLUSION: Adalimumab is a well tolerated and effective treatment for patients with RA, even when infliximab has been discontinued.
17325584 Radiation synovectomy using 188Re-tin colloid improves knee synovitis as shown by MRI in r 2007 Apr BACKGROUND: Radiation synovectomy is a useful local treatment for patients with refractory synovitis. We previously demonstrated the efficacy and safety of Re-tin colloid for treating rheumatoid arthritis patients with refractory knee synovitis. This open-label, prospective controlled study investigates magnetic resonance imaging (MRI) changes as well as clinical response in knees after receiving different radioactivities of intra-articular Re-tin colloid. METHODS: Sixteen patients with rheumatoid arthritis refractory to intra-articular corticosteroid therapy were treated with intra-articular injection of Re-tin colloid (555 MBq in six patients, 740 MBq in five, and 925 MBq in five). Contralateral knees were used as controls. Treatment efficacy and safety were evaluated 1, 3 and 6 months later. We compared the changes of synovial thickening and joint effusion between baseline and 6 months. Synovial thickness was measured by gadolinium-enhanced MRI. RESULTS: Pain intensities on a visual analogue scale were significantly lower (median pain reduction, 78.9%; P=0.0001), joint swelling improved (median, -1.5; P=0.001), range of motion increased (median, 6 degrees , P=0.005), and joint tenderness decreased (median, -1; P=0.005) in treated knees after 6 months. The control knees did not show any significant clinical improvement. At 6 months after therapy, synovial thickening of treated knees improved in 87.5% of patients (P<0.001), and synovial thicknesses were significantly decreased in treated knees (P=0.0067). Furthermore, reduction in synovial thickness was most noticeable in the group treated with 925 MBq (P=0.007). No abnormalities in leukocyte or platelet counts, liver function tests, or urine analysis were observed. CONCLUSION: Radiation synovectomy using Re-tin colloid in refractory rheumatoid arthritis patients improved MRI findings as well as clinical parameters.
17546224 [Polymorphisms of IL-10 gene promoter and rheumatoid arthritis in a Colombian population]. 2007 Mar INTRODUCTION: Rheumatoid arthritis is an inflammatory disease driven by TH1 CD4+ cells. Interleukin-10 is present in higher concentrations in serum and synovial fluid from patients with rheumatoid arthritis and has a marked anti-inflammatory activity. Furthermore, it is capable of stimulating B cells and increasing autoantibody production. Interleukin-10 synthesis is under genetic control. OBJECTIVE: Three polymorphisms of the promoter region were analyzed for interleukin-10 genes -1082, -819 and -592. Subjects were patients with rheumatoid arthritis compared with a control population for these genes. MATERIAL AND METHODS: One hundred two patients with rheumatoid arthritis and 102 matched healthy controls were studied. The following data were taken from the rheumatoid arthritis patients: age of disease onset, presence and titers of rheumatoid factor, and history of replacement joint surgery. Genotypes were obtained by polymerase chain reaction and sequence-specific primer method. The three polymorphisms are in strong linkage-disequilibrium and form three haplotypes -1082A/-819C/-592C, -1082A/-819T/-592A y -1082G/-819C/-592C. RESULTS: No association was detected between Interleukin-10 alleles, haplotypes/genotypes and rheumatoid arthritis. No significant differences occurred between interleukin-10 polymorphisms and age of disease onset, presence and titer of rheumatoid factor and history of major joint replacement. CONCLUSIONS: Interleukin-10 is an important regulator of the immune response and likely plays a role in the pathogenesis of rheumatoid arthritis. The current results suggested that Interleukin-10 promoter polymorphisms were not important for development or severity of rheumatoid arthritis.