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ID PMID Title PublicationDate abstract
17985418 Predictive markers in rapidly progressing rheumatoid arthritis. 2007 Nov The emphasis in rheumatoid arthritis (RA) management today is on early diagnosis and intervention, but the choice of intervention has become increasingly complex. The number of disease modifying antirheumatic drugs available for treatment of RA has increased significantly. The efficacy, toxicity, and cost of those agents vary widely. And the progression of joint damage in RA is highly unpredictable and variable, ranging from self-limited disease to rapid progressive destruction. Prognostic markers that could identify patients with aggressive, rapidly progressing disease and predict the response to therapy would provide a rational basis for early, aggressive treatment. They would also protect patients with less aggressive disease from possible overtreatment and toxicities, and could have a significant influence on allocation of healthcare resources. The search for predictive markers of arthritis outcome has been and undoubtedly will continue to be the subject of many studies. This article will review both established and emerging predictive markers in RA.
16133581 Inhibitory effect of bone resorption and inflammation with etidronate therapy in patients 2006 May This study was conducted to identify bone resorption and anti-inflammatory effects with intermittent cyclical etidronate therapy (ICET) in patients with rheumatoid arthritis, and anti-inflammatory effect of etidronate in vitro. We compared bone mineral density (BMD), urinary deoxypyridinoline (DPD) level, bone alkaline phosphatase (BAP) level and Larsen damage scores between the ICET and the non-ICET groups for 3 years. The levels of interleukin-6 (IL-6), prostaglandin E2 (PGE2), substance P and vascular endothelial growth factor (VEGF) in synovial cells from arthritis models were measured following the addition of etidronate. In the ICET group, BMD and BAP levels increased. Urinary DPD level and the Larsen damage score were significantly lower than that in the non-ICET group. In the in vitro study, the production of IL-6, PGE2, substance P and VEGF were inhibited in a dose-dependent manner. Bone resorption and destruction inhibition effect of etidronate remained for 3 years. In vitro study showed that the production of inflammatory cytokines and an angiogenesis factor were inhibited.
18817640 Are spondyloarthropathies as common as rheumatoid arthritis worldwide? A review. 2008 Oct The high-range estimate of 1.3% by the National Arthritis Data Workgroup for the prevalence of the entire spectrum of spondyloarthropathies (SpAs) suggests that SpAs may be more prevalent than rheumatoid arthritis (RA) in the United States. Recent surveys from many European countries using the same sample population have also found SpA to be at least as common as RA in most of the studied populations, including Finnish, Swedish, Lithuanian, French, Italian, and Turkish. Among Asian populations, China has the highest prevalence of SpA, with reported estimates generally higher than that of RA. In Thailand and Vietnam, the two diseases are probably equally common, whereas RA seems to be more prevalent than SpA in the rest of Asia, the Pacific Region, and Latin America, as indicated by studies following the COPCORD (Community-Oriented Program for the Control of Rheumatic Diseases) protocol. Both rheumatic disorders are rare in Africa, but SpA is less common than RA.
16091838 Pulmonary involvement in lifelong non-smoking patients with rheumatoid arthritis and ankyl 2006 Mar Pulmonary involvement seen in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) has been detected increasingly by using highly sensitive diagnostic techniques such as high-resolution computed tomography (HRCT). However, HRCT findings in healthy controls and the effects of smoking and drugs have not been well studied. The aim of this controlled study was to evaluate the relationships between disease-specific clinical, laboratory, HRCT and pulmonary function test (PFT) findings in 20 RA patients using methotrexate (MTX) and 20 AS patients using sulphasalazine who were non-smokers and exhibited asymptomatic respiratory signs. For this purpose, a total of 60 persons (40 patients and 20 healthy controls) were included in this study. A restrictive pattern on PFT was detected in four patients (20%) with AS, one patient with RA and one control (p<0.05). Fourteen patients (70%) with RA and ten patients (50%) with AS had positive HRCT findings. Only one patient (5%) in the control group had abnormal HRCT findings (p<0.05). Interstitial lung disease (ILD) was the most frequently seen HRCT finding in both the RA (35%) and AS (20%) groups. The chest expansion measurement, the score of the visual analogue scale (VAS) for pain and C-reactive protein (CRP) levels were statistically significantly better in patients with AS having normal HRCT than in those with abnormal findings (p<0.05). There was no correlation detected between HRCT and duration of disease, disease activity markers, functional indexes and PFT in patients with RA and AS. HRCT is a sensitive tool in detecting ILD in patients with RA and AS with no signs and symptoms of pulmonary involvement and may be an integral part of such work-up. However, future prospective studies are needed to better determine if HRCT is in fact a predictor of subsequent MTX toxicity.
16672862 Bone graft for tibial defects in total knee arthroplasty. 1986. 2006 May Twenty-four knees with bone grafts for tibial defects at the time of either primary or revision total knee arthroplasty were followed for three to six years. With 22 of 24 bone grafts, union and revascularization were seen and no clinical collapse was present. In two, nonunion occurred, accompanied by collapse in one. Failure was attributed to varus alignment of the leg in one (a medial condylar graft) and to insufficient preparation of the bony bed in the second (bleeding bone was not exposed). Evidence for incorporation of the grafts was obtained by tomogram, bone scan, and bone biopsy. Incorporation was present by six months, but the time to complete remodeling was not determined. A bone graft is recommended for tibial defect involving 50% or more of the bony support of either tibial plateau. A bone graft is indicated whenever a cement column under the prosthesis would measure more than 5 mm in height.
18566445 B lymphocyte autoimmunity in rheumatoid synovitis is independent of ectopic lymphoid neoge 2008 Jul 1 B lymphocyte autoimmunity plays a crucial role in the pathogenesis of rheumatoid arthritis. The local production of autoantibodies and the presence of ectopic lymphoid neogenesis in the rheumatoid synovium suggest that these dedicated microenvironments resembling canonical lymphoid follicles may regulate the initiation and maturation of B cell autoimmunity. In this study, we assessed experimentally the relevance of ectopic lymphoid neogenesis for B cell autoimmunity by a detailed structural, molecular, and serological analysis of seropositive and seronegative human synovitis. We demonstrate that synovial lymphoid neogenesis is a reversible process associated with inflammation which is neither restricted to nor preferentially associated with autoantibody positive rheumatic conditions. Despite the abundant expression of key chemokines and cytokines required for full differentiation toward germinal center reactions, synovial lymphoid neogenesis in rheumatoid arthritis only occasionally progresses toward fully differentiated follicles. In agreement with that observation, we could not detect Ag-driven clonal expansion and affinity maturation of B lymphocytes. Furthermore, ectopic lymphoid neogenesis is not directly associated with local production of anti-citrullinated protein Abs and rheumatoid factor in the rheumatoid joint. Therefore, we conclude that synovial lymphoid neogenesis is not a major determinant of these rheumatoid arthritis-specific autoantibody responses.
17762458 Spontaneous rupture of ulnar nerve due to neglected cubital tunnel syndrome associated wit 2007 Aug A case of spontaneous rupture of the ulnar nerve due to neglected cubital tunnel syndrome associated with rheumatoid arthritis is reported. Earlier decompression and anterior transposition in this patient may have prevented nerve rupture.
16793145 Adenoviral delivery of IL-1 receptor antagonist abrogates disease activity during the deve 2006 Aug 15 Currently available treatments for rheumatoid arthritis (RA) are limited in terms of their long-term effects and their abilities to control disease progression. Interleukin-1 receptor antagonist (IL-1Ra) is a natural inhibitor of the biologic actions of IL-1, which is known to promote inflammation and degeneration of the joint. In this study, we investigated whether human IL-1Ra gene transfer is effective at treating an established experimental arthritis model. A recombinant adenovirus carrying the gene that encode human hIL-1Ra and GFP (Ad.hIL-1Ra/GFP) was administered by intra-articular injection into the ankle joints of the mice with established the IL-1Ra-deficient Balb/cA mice (IL-1Ra(-/-)), which develop spontaneously chronic inflammatory arthropathy. The effects of two injections of Ad.hIL-1Ra/GFP or control virus with no inserted target gene (Ad.GFP) were compared with the effects of PBS injection with respect to the clinical characteristics of arthritis, as determined by articular index scores, histopathological and immunological assays. We further divided the outcomes of Ad.hIL-1Ra/GFP gene therapy in IL-1Ra(-/-) mice according arthritis stage; early stage and chronic stage corresponding to 8 and 15 weeks of age, respectively. Intra-articular injections of Ad.hIL-1Ra/GFP reduced arthritis severity and footpad swelling compared with control groups treated with Ad.GFP or PBS in early stage IL-1Ra(-/-) mice. Moreover, the histopathology of the ankle joints of IL-1Ra(-/-) mice treated with Ad.hIL-1Ra/GFP showed a significant decrease in synovial proliferation and inflammatory cell infiltration, and preserved proteoglycan levels in the joints of early stage IL-1Ra(-/-) mice compared with the control mice. Moreover, Ad.hIL-1Ra/GFP treated mice showed reduced levels of inflammatory T helper type 1 (Th1) driven IgG2a antibodies to collagen type II but increased levels Th2 driven IgG1 antibody. These results suggest that adenovirus-mediated gene transfer of IL-1Ra may be a promising therapeutic option in the early stage of autoimmune arthritis.
19037610 The comparison of ultrasonographic and scintigraphic findings of early arthritis in reveal 2009 May We aimed to investigate the diagnostic significance of high frequency ultrasonography (USG), comparing the findings in USG, bone scintigraphy and clinical stuation. Fifty-one patients who had early symptoms of inflammatory arthritis, but not fulfilling the ACR diagnostic criteria for rheumatoid arthritis (RA) were included in this study. They were referred to USG and bone scintigraphy for examination of the synovial joints. After following at least 2 years with visits at every 3 months, those who fulfilled the ACR criteria for the diagnosis of RA were defined as reference group. The concordance levels were assessed with Kappa statistic among them. The diagnosis of inflammatory arthritis that was made with USG in early time showed average agreement with the diagnosis according to ACR criteria. However, there was statistically discordance between the diagnosis of inflammatory arthritis that was made with bone scintigraphy in early time and the diagnosis according to ACR criteria.
18375540 Changes in hand and generalised bone mineral density in patients with recent-onset rheumat 2009 Mar OBJECTIVES: To evaluate changes in bone mineral density (BMD) in the hands, hip and spine after 1 and 2 years of follow-up, in relation to antirheumatic and antiresorptive therapies and disease and demographic variables in patients with recent-onset rheumatoid arthritis (RA). METHODS: Changes in BMD measured in metacarpals 2-4 by digital x-ray radiogrammetry and in the hip and spine by dual energy x-ray absorptiometry were assessed at baseline and after 1 and 2 years of follow-up in 218 patients with recent-onset RA from the BeSt study, who received one of four treatment strategies: sequential monotherapy (group 1); step-up combination therapy (group 2); initial combination therapy with tapered high-dose prednisone (group 3); or initial combination therapy with infliximab (group 4). RESULTS: After 1 and 2 years, there was significant BMD loss in all locations, with significantly greater BMD loss in the hands than generalised BMD loss in the hip and spine. Initial combination therapy with prednisone or infliximab were associated with less hand BMD loss compared with initial monotherapy after 1 and 2 years (-0.9 and -1.6%, -0.6 and -1.4%, -1.7 and -3.3%, and -2.6 and -3.6% for group 4-1 after 1 and 2 years, overall p = 0.001 and p = 0.014, respectively). Progression in erosions was independently associated with increased BMD loss both in the hands and hip after 1 year. The use of bisphosphonates protected only against generalised BMD loss in the hip and spine. CONCLUSIONS: The association between joint damage progression and both hand and generalised BMD loss in RA suggests common pathways between these processes, with hand BMD loss occurring earlier in the disease course than generalised BMD loss.
18006645 Regulation of lysophosphatidic acid receptor expression and function in human synoviocytes 2008 Feb Lysophosphatidic acid (LPA), via interaction with its G-protein coupled receptors, is involved in various pathological conditions. Extracellular LPA is mainly produced by the enzyme autotaxin (ATX). Using fibroblast-like synoviocytes (FLS) isolated from synovial tissues of patients with rheumatoid arthritis (RA), we studied the expression profile of LPA receptors, LPA-induced cell migration, and interleukin (IL)-8 and IL-6 production. We report that FLS express LPA receptors LPA(1-3). Moreover, exogenously applied LPA induces FLS migration and secretion of IL-8/IL-6, whereas the LPA(3) agonist l-sn-1-O-oleoyl-2-methyl-glyceryl-3-phosphothionate (2S-OMPT) stimulates cytokine synthesis but not cell motility. The LPA-induced FLS motility and cytokine production are suppressed by LPA(1/3) receptor antagonists diacylglycerol pyrophosphate and (S)-phosphoric acid mono-(2-octadec-9-enoylamino-3-[4-(pyridine-2-ylmethoxy)-phenyl]-propyl) ester (VPC32183). Signal transduction through p42/44 mitogen-activated protein kinase (MAPK), p38 MAPK, and Rho kinase is involved in LPA-mediated cytokine secretion, whereas LPA-induced cell motility requires p38 MAPK and Rho kinase but not p42/44 MAPK. Treatment of FLS with tumor necrosis factor-alpha (TNF-alpha) increases LPA(3) mRNA expression and correlates with enhanced LPA- or OMPT-induced cytokine production. LPA-mediated superproduction of cytokines by TNF-alpha-primed FLS is abolished by LPA(1/3) receptor antagonists. We also report the presence of ATX in synovial fluid of patients with RA. LPA(1/3) receptor antagonists and ATX inhibitors reduce the synovial fluid-induced cell motility. Together the data suggest that LPA(1) and LPA(3) may contribute to the pathogenesis of RA through the modulation of FLS migration and cytokine production. The above results provide novel insights into the relevance of LPA receptors in FLS biology and as potential therapeutic targets for the treatment of RA.
18402714 The multi-faceted assessment of independence in patients with rheumatoid arthritis: prelim 2008 May OBJECTIVE: To consider the feasibility of assessing multiple facets of independence in rheumatoid arthritis (RA) using a measure developed from existing items and examining its face validity, construct validity and responsiveness to change. METHODS: The ATTAIN (Abatacept Trial in Treatment of Anti-tumor necrosis factor [TNF] Inadequate responders) database was used. Patients with RA were randomized 2:1, abatacept (n = 258) and placebo (n = 133). A multi-faceted scale to measure physical and psychosocial independence was constructed using items from the Health Assessment Questionnaire (HAQ) and Short Form 36 Health Survey (SF-36). Questions assessing activity limitations and need for outside caregiver help were also examined. Interviews with 20 RA patients assessed face validity. RESULTS: Item Response Theory analysis yielded two traits - 'Psychosocial Independence', derived from the number of days with activity limitations plus the Role Emotional, Social Functioning and Role Physical subscale items from the SF-36; and 'Physical Independence', derived from 15 HAQ items assessing need for help from another. The two traits showed no significant differential item functioning for age or gender and demonstrated good face validity. Changes over 169 days on Psychosocial Independence were greater (mean 0.46 units, 95% confidence interval [CI]: 0.17-0.75) for the abatacept group than for placebo (p = 0.002). Changes in Physical Independence were greater (mean 0.59 units, 95% CI: 0.35-0.82) for the abatacept group than for placebo (p < 0.001). CONCLUSIONS: The multi-faceted assessment of independence in RA based on items from commonly used instruments is feasible suggesting promise for evaluating independence in future clinical trials. This approach demonstrated good face and construct validity and responsiveness in RA patients who had previously failed anti-TNF therapy. However, we caution against an interpretation that these data suggest that abatacept improves independence because the component parts of this assessment came from instruments used in the ATTAIN trial where data had been previously analyzed.
19024279 [The efficacy and safety of the combination of leflunomide (Arava) and biological agents i 2008 The efficacy and safety of the combination of leflunomide (Arava) with biological agents in treatment of rheumatoid arthritisiare presented.
16339291 Baseline comorbidity levels in biologic and standard DMARD treated patients with rheumatoi 2006 Jul OBJECTIVE: To describe the occurrence of baseline comorbidity in subjects with active rheumatoid arthritis starting treatment with biological agents. Such data are necessary to interpret the reported occurrence of adverse events following treatment. METHODS: Baseline comorbidity was recorded in a large national cohort of patients with rheumatoid arthritis newly starting biological agents. The distribution of the number and types of comorbidities is presented. RESULTS: In all, 7818 patients treated with biological agents (infliximab 3332, etanercept 3302, adalimumab 1059, anakinra 132) were included in the analysis. Comorbidity was common, with 58% of patients having at least one comorbid condition and 25% having more than one. The most frequent comorbid conditions were hypertension, depression, peptic ulcer disease, and respiratory disease. CONCLUSIONS: In routine use, patients treated with biological agents have high levels of baseline comorbidity, which should influence the interpretation of reported adverse events.
18590106 [Early diagnosis of rheumatoid arthritis in modern clinical practice (results of a follow- 2008 AIM: To estimate potentialities of early diagnosis of rheumatoid arthritis (RA) diagnosis in clinical practice in the course of the RADICAL program. MATERIAL AND METHODS: Of 366 patients participating in the trial 61 (16.7%) were males and 305 (83.3%) were females at the age of 47.76 +/- 14.1 years. The longest duration of the symptoms before consulting a doctor was 51 weeks, mean duration--5.7 weeks, 55% patients had the symptoms for 3 weeks. All the patients have undergone laboratory examination including leukocyte count, platelet count, estimation of ESR, concentration of C-reactive protein (CRP), rheumatoid factor (RF) and antibodies to a cyclic citrullated peptide (ACCP); roentgenography of the wrists and feet. On demand, antinuclear factor (ANF) and HLA-B27 were investigated. RA was diagnosed on the basis of ACR classification criteria. If the criteria were not complete at the moment of the study, the patient was referred to the group of "undifferentiated arthritis" (UA). The patients were examined before the treatment, 6 and 12 months later. The treatment was made according to Russian clinical recommendations. RESULTS: Prior to admission to hospital, 58% patients were suspected for RA, 18.3%--osteoarthrosis (OA), 14%--reactive arthritis. 18.9% were not diagnosed, other diagnoses were considered in 12.6% patients. At primary examination RA was diagnosed in 212 (57.9%) patients, UA was in 133 (36.3%) patients, 21 (5.7%) patients had other diagnoses. Twelve months later RA, UA and other diseases were diagnosed in 256 (69.9%), 70 (19.1%) and 40 (10.9%) patients, respectively. CONCLUSION: A 3-stage algorithm of early RA diagnosis is proposed. At the stage of the first contact with the patient in an outpatient clinic a valid RA suspition with consideration of modified EULAR criteria must be formulated. At the second stage a district rheumatologist must examine the patient outpatiently with determination of ACR classification criteria. In diagnosis verification the treatment must be started according to APP and EULAR clinical recommendations. If RA diagnosis can not be verified or rejected, the patient must be refered to hospital (stage 3). If verification of RA diagnosis is impossible, the diagnosis should be formulated as UA.
19117726 Familial disease, the HLA-DRB1 shared epitope and anti-CCP antibodies influence time at ap 2009 Feb Rheumatoid arthritis (RA) progresses more rapidly in some patients than in others and diverse factors influence radiographic progression in a specific population. Thus, we searched for variables that are associated with an early appearance of substantial joint damage in patients with RA by using radiographic assessments. A cohort of 157 consecutively enrolled Colombian RA patients was followed for an average of 3.2+/-3.1 years. Information on patient demographics and cumulative clinical and laboratory manifestations over the course of the disease was registered, including family history of RA in first-degree relatives, extra-articular manifestations, rheumatoid factor, anti-CCP3 antibodies, TNF single nucleotide polymorphism at -308 position, and HLA-DRB1 status. Radiographs were scored according to the Sharp-van der Heijde method. Survival analyses of the time at appearance of substantial joint damage were performed by using Weibull models. A review of literature about the influence of familial RA on the progression of disease was done. Our results show that family history of RA is consistently associated with joint damage (i.e. erosive and joint narrowing disease). This effect was not found in all the populations reviewed. In addition, we confirm the effect of HLA-DRB1 shared epitope and anti-CCP seropositivity on erosive disease. Family history of RA is a key risk factor for joint damage and depends on the investigated population because variations in both additive and non-additive genetic factors and the environmental variance are specific to the population. Our results emphasize the usefulness of assessing familial disease, testing anti-CCP antibodies and genotyping HLA-DRB1 gene in patients with RA because these factors may be used to predict clinical outcomes and guide therapeutic interventions.
17135225 The 620W allele is the PTPN22 genetic variant conferring susceptibility to RA in a Dutch p 2007 Apr OBJECTIVES: A missense SNP, C1858T, in PTPN22 has been identified as a genetic risk factor for rheumatoid arthritis (RA). Subsequent work has suggested that other variants in this gene, in particular a haplotype marked by the minor allele of rs3789604, are associated with RA in white North Americans independent of C1858T. We tested this hypothesis in an independent white Dutch study. METHODS: A total of 667 RA patients and 286 controls were genotyped for 13 PTPN22 single nucleotide polymorphisms (SNPs) by allele-specific kinetic polymerase chain reaction. rs3789604 was genotyped in an additional 410 RA and 270 UA patients participating in the Leiden early arthritis inception cohort. We conducted single-marker and haplotype association tests. RESULTS: The sole haplotype strongly associated with RA in our Dutch population carries the PTPN22 1858T allele. A second haplotype identical at all other SNPs tested except 1858 was not associated with disease. No significant association of the haplotype tagged by the 3' PTPN22 SNP, rs3789604, with RA susceptibility (P = 0.134) was observed in our sample set. CONCLUSION: We conclude that C1858T is the sole PTPN22 variant predisposing to RA in our white Dutch sample set.
17145392 Fractional flexor tendon lengthening for advanced metacarpophalangeal flexion contracture 2006 Dec This technical report discusses a subgroup of rheumatoid patients who have minimal ulnar drift but a severe fixed metacarpophalangeal joint flexion contracture for whom conventional metacarpophalangeal joint arthroplasty alone was insufficient to correct the deformity. We describe a surgical technique to deal with this clinical problem that uses fractional flexor tendon lengthening in the forearm to correct the severe flexion deformity at the metacarpophalangeal joint.
17204385 Treatment with total alkaloids from Radix Linderae reduces inflammation and joint destruct 2007 May 4 Radix Linderae, the dry roots of Lindera aggregata (Sims) Kosterm., is frequently used in traditional Chinese medicine. It contains alkaloids, volatile oils and sesquiterpene esters. In the present study, we investigated the therapeutic potential and underlying mechanisms of the total alkaloids from Radix Linderae (TARL) on collagen II (CII)-induced arthritis (CIA) in mice. TARL (50, 100 and 200mg/kg), orally administered on the same day of an antigen challenge for 20 consecutive days, alleviated disease severity in a dose-dependent manner but did not significantly affect body weights. The TARL treatment reduced the serum level of anti-CII IgG and suppressed the delayed type hypersensitivity evaluated by its effect against CII-induced ear swelling. TARL also protected joint destruction based on the evidence of reducing the histopathological scores. Furthermore, TARL suppressed CII- and concanavalin A-stimulated lymphocyte proliferation in popliteal lymph nodes, where are close to the affected joints in CIA. These data suggest that TARL is a potential therapeutic agent for rheumatoid arthritis that suppresses inflammation and protects joints from destruction.
16394654 Tumor necrosis factor ligand-receptor superfamily and arthritis. 2006 The current studies of apoptosis in rheumatoid arthritis (RA) suggest that the TNF ligand-receptor superfamily (TNFRsF) molecules, downstream pathways (activation of proapoptosis or anti-apoptosis pathway), cell types (lymphocytes and synovial fibroblast), and the mechanism that triggers apoptosis (tolerance induction-related, downmodulation of inflammation-related, or DNA damage-related) all exhibit a capability to determine the induction or prevention of RA. This series of defects at different levels and in different cells have been shown to lead to T cell and synovial hyperproliferation, defective apoptosis, excessive apoptosis, or bone erosion. In this chapter, we summarize the available knowledge of the regulation of TNFRsF and their likely pathogenic roles in RA to help identify candidate target cells and target molecules for delivery of gene constructs to modulate apoptosis to prevent the development of RA in both humans and mice.