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ID PMID Title PublicationDate abstract
20507365 Effect of Porphyromonas gingivalis-induced inflammation on the development of rheumatoid a 2010 May BACKGROUND: Periodontitis is an extra-synovial chronic inflammatory condition, which has been proposed to be inter-related with rheumatoid arthritis. OBJECTIVE: We investigated the effect of an established extra-synovial chronic inflammatory lesion on the induction and severity of experimental arthritis. MATERIALS AND METHODS: Chronic inflammatory lesions were induced by the implantation of polyurethane sponges impregnated with heat-killed Porphyromonas gingivalis into the backs of DA rats. Thirty-five days later, adjuvant arthritis (AA) was induced in the rats by injecting a mycobacterium cell wall in complete Freund's adjuvant. The development of arthritis was then monitored for 2 weeks. RESULTS: Histological assessment of the implanted sponges confirmed that a chronic inflammatory lesion had been established after 21 days. Following induction of adjuvant arthritis, the severity of disease was scored and paw swelling was measured. Severe arthritis developed more rapidly in animals with a pre-existing P. gingivalis-induced inflammatory lesion elsewhere. CONCLUSIONS: The results show that a pre-existing extra-synovial chronic inflammatory lesion induced by P. gingivalis promotes the development of arthritis in an animal model. These findings provide further evidence for a relationship between the presence of periodontal pathogen-associated inflammation and the development of rheumatoid arthritis.
19501300 Surgical management of septic arthritis of the knee with a coexistent popliteal cyst. 2009 Jun We report a case of knee pyarthrosis in a 54-year-old woman with rheumatoid arthritis and a popliteal cyst. The onset of infection coincided with a cortisone injection. Initial management consisted of arthroscopic irrigation and debridement (I&D) on 2 consecutive occasions without resolution of the infection. Only after open excision of the popliteal cyst in conjunction with I&D of the knee joint proper did the infection resolve. This is the first reported case of a patient requiring excision of a popliteal cyst to clear pyarthrosis of the knee after failure of arthroscopic I&D. Consideration should be given to open debridement or drainage of popliteal cysts in patients who present with septic arthritis in the presence of a popliteal cyst. A treatment algorithm for managing this clinical scenario is presented.
19333986 Understanding why rheumatoid arthritis patient treatment preferences differ by race. 2009 Apr 15 OBJECTIVE: Rheumatoid arthritis (RA) patient preferences may account for some of the variability in treatment between racial groups. How and why treatment preferences differ by race is not well understood. We sought to determine whether African American and white RA patients differ in how they evaluate the specific risks and benefits related to medications. METHODS: A total of 136 RA patients completed a conjoint analysis interactive computer survey to determine how they valued the specific risks and benefits related to treatment characteristics. The importance that respondents assigned to each characteristic and the ratio of the importance that patients attached to overall benefit versus overall risk were calculated. Subjects having a risk ratio <1 were classified as being risk averse. RESULTS: The mean age of the study sample was 55 years (range 22-84). Forty-nine percent were African American and 51% were white. African American subjects assigned the greatest importance to the theoretical risk of cancer, whereas white subjects were most concerned with the likelihood of remission and halting radiographic progression. Fifty-two percent of African American subjects were found to be risk averse compared with 12% of the white subjects (P < 0.0001). Race remained strongly associated with risk aversion (adjusted odds ratio [95% confidence interval] 8.4 [3.1, -23.1]) after adjusting for relevant covariates. CONCLUSION: African American patients attach greater importance to the risks of toxicity and less importance to the likelihood of benefit than their white counterparts. Effective risk communication and improved understanding of expected benefits may help decrease unwanted variability in health care.
20299184 Long-term survivorship analysis of the cementless Spotorno femoral component in patients l 2011 Apr The long-term survival of the cementless Spotorno (CLS) femoral component (Zimmer Inc, Warsaw, USA) was evaluated in a consecutive series of 85 patients (100 hips) less than 50 years of age. The mean follow-up was 12.3 years. Two patients (3 hips) were lost to follow-up, and 3 (4 hips) died. The survival rate of the CLS stem was 96.9% (confidence interval [CI], 93.6%-100%) after 13 years based on revision of the stem for any reason. The survival of the stem with revision for aseptic loosening as the end point was 97.9% (CI, 95.1%-100%) at 13 years. The mean Harris hip score at time of follow-up was 94. The long-term survival of the CLS stem is excellent in patients less than 50 years of age.
19727044 Neutrophils: warriors and commanders in immune mediated inflammatory diseases. 2009 Apr Neutrophils are critical effector cells in the immune system. They not only play crucial roles in pathogenic defense but are also able to modulate the function of other immune cells and consequently contribute to the immune response fate. The herein review is focused in neutrophil biology in a general perspective and its contribution to the course of immune mediated inflammatory diseases.
20542961 Rabeximod reduces arthritis severity in mice by decreasing activation of inflammatory cell 2010 Aug OBJECTIVES: The novel small molecule 9-chloro-2,3-dimethyl-6-(N,N-dimethylaminoethylamino-2-oxoethyl)-6H-indolo[2,3-b] quinoxaline (Rabeximod) reduces severity of arthritis in rodent models of rheumatoid arthritis (RA) and multiple sclerosis (MS). This study aimed to investigate the cellular target in vivo. METHODS: Collagen antibody-induced arthritis (CAIA) is induced by monoclonal collagen type II antibodies and enhanced by lipopolysaccharide. It was investigated how and when Rabeximod operates on inflammatory cells after stimulation of either Toll-like receptor (TLR)4 (lipopolysaccharide) or TLR2 (lipomannan) in mice lacking functional signalling through TLR4 due to a spontaneous deletion of the Tlr4 gene. RESULTS: Rabeximod efficiently prevented arthritis during the time window when TLR2 or TLR4 ligands activate inflammatory macrophages. The effect operated downstream of TLR activation as Rabeximod was highly therapeutic in CAIA enhanced through TLR2 stimuli in TLR4 deficient mice. In addition, it was found that the arthritis ameliorating effect of Rabeximod was time dependent, since inhibition of tumour necrosis factor alpha production from macrophages in vitro was more pronounced if administered close to stimulation. CONCLUSIONS: Rabeximod suppresses arthritis by preventing activation of inflammatory cells, most likely macrophages, in a time dependent fashion, downstream of TLR2 and TLR4 stimulation.
19583105 First reported United States case of Legionella pneumophila serogroup 1 pneumonia in a pat 2009 Jun Legionellosis has been reported to be an extremely rare disease in Hawai'i. The authors report a case of a 67-year-old woman with a history of rheumatoid arthritis treated with long-term adalimumab who developed severe right-sided community-acquired pneumonia and a parapneumonic effusion. Legionella pneumophila serogroup 1 was confirmed as the microbiologic cause based on a positive urine Legionella antigen as well as direct fluorescent antibody and Legionella culture of bronchoalveolar lavage. This is the first reported case of Legionella pneumonia associated with anti-tumor necrosis factor (TNF)-alpha therapy in the United States. There have been several reports of an increased association between legionellosis and treatment with a TNF-alpha antagonist. With the increasing use of TNF-alpha antagonists, Legionella pneumophila should be recognized as a potential re-emerging pathogen. Clinicians should particularly consider the diagnosis of legionellosis in patients who are immunocompromised, including those who receive anti-TNF-alpha therapy, or who have severe pneumonia. In such cases, there should be a low threshold for including empiric Legionella antimicrobial coverage until the diagnosis can be confirmed or reasonably excluded.
19861018 QuantiFERON-TB Gold in the identification of latent tuberculosis infection in rheumatoid a 2009 Nov OBJECTIVE: To compare the performance of QuantiFERON-TB Gold (QFT-G) with that of the tuberculin skin test (TST) in detecting latent tuberculosis (LTBI) among patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: A total of 35 RA patients and 15 healthy controls underwent TST, QFT-G assays and chest X-ray and filled out a questionnaire on predisposing conditions for TB disease. Serum interferon gamma (IFN-gamma) levels were tested by an enzyme-linked immunosorbent assay. RESULTS: Forty-five per cent of RA patients had a TST > 5 mm vs. 26% in healthy controls. In the RA patients, QFT-G was positive in 11.4%, negative in 60% and indeterminate in 28.6%. The overall agreement between TST and QFT-G was significantly lower in the RA population than in controls (56% vs. 84%). No correlation was found between the use of prednisone, methotrexate and QFT-G results or agreement between TST and QFT-G. A low IFN-gamma level (<4 pg/ml) was found in 51.5% of the RA patients. No correlation was found between serum IFN-gamma levels and QFT-G results. CONCLUSION: The clinical significance of negative QFT-G in TST-positive patients with low TB risk remains to be assessed. The high rate of indeterminate results questions the clinical utility of QFT-G in the diagnosis of LTBI in RA patients.
19208686 Association analysis of the interleukin 17A gene in Caucasian rheumatoid arthritis patient 2009 Apr OBJECTIVE: Elevated levels of IL-17A have been detected in the inflamed synovium of RA patients, and murine arthritis models deficient in IL17A have shown reduced inflammation. Our aim was to investigate IL17A as a candidate gene for RA, and to assess correlations between risk variants and disease phenotypes. METHODS: Five single nucleotide polymorphisms (SNPs) were selected to tag the genetic variability of the IL17A region and were genotyped by TaqMan technology on 950 RA cases and 933 random controls from Norway. Associations to progression of radiographic damage and presence of autoantibodies were examined in a 10-yr follow-up cohort of early RA. In addition, 580 RA patients and 504 controls from New Zealand were used as a replication data set. RESULTS: A weak association between RA and the promoter SNP rs2275913 [odds ratio (OR) = 1.17; 95% CI 1.02, 1.34; P = 0.02] was found in the Norwegian population. The association was also evident at the genotype level where it indicated a recessive model. The allelic association was not replicated in the RA cohort from New Zealand (OR = 0.96; 95% CI 0.81, 1.16; P = 0.69). However, combined analysis suggested a weak recessive association (OR = 1.19; 95% CI 1.02, 1.37; P = 0.02). No significant associations were observed with radiographic progression, anti-cyclic citrullinated peptide or IgM-RF. CONCLUSIONS: Modest evidence of an association with IL17A in Norwegian RA patients was observed. Although, our findings were not replicated in an independent RA material from New Zealand, a significant common risk estimate indicated that IL17A warrants further investigation in RA.
20510241 Cardiovascular complications of rheumatoid arthritis: assessment, prevention, and treatmen 2010 May Morbidity and mortality rates are higher in individuals with rheumatoid arthritis (RA) than in the general population. Ischemic heart disease and heart failure now represent one of the most common causes of death in RA. Indeed, RA appears to represent an independent risk factor for ischemic heart disease, similar to diabetes mellitus. However, no clear guidelines with regard to cardiovascular disease diagnosis and prevention in RA have been developed. This review highlights recent investigations on the assessment, prevention, and treatment of cardiovascular disease in RA.
20803354 Systematic review of patellar resurfacing in total knee arthroplasty. 2011 Mar Controversies existing over resurfacing the patella in total knee arthroplasty remain in the literature. The purpose of this review was to evaluate the effectiveness of resurfacing versus nonresurfacing the patella in total knee arthroplasty. We searched the Cochrane Library, MEDLINE and EMBASE for published randomised clinical trials relevant to patellar resurfacing. The relative risk of reoperation was significantly lower for the patellar resurfacing group than for the nonresurfacing group (relative risk 0.57, 95% confidence interval 0.38-0.84, P =0.004). The overall incidence of postoperative anterior knee pain of the 1,421 knees included was 12.9% in the patellar resurfacing group and 24.1% in the nonresurfacing group. The existing evidence indicates that patellar resurfacing can reduce the risk of reoperation with no improvement in postoperative knee function or patient satisfaction over total knee arthroplasty without patellar resurfacing. Whether it can decrease the incidence of anterior knee pain remains uncertain.
20108016 Osteoarthritis: can anti-cytokine therapy play a role in treatment? 2010 May Osteoarthritis (OA) is the most common joint disorder worldwide, and it has an enormous socioeconomic impact both in the United States and throughout the world. The degree of articular inflammation is usually associated with the disease's progression, indicating that this process could contribute to articular damage. IL-1 beta and anti-TNF alpha are the two major cytokines players in the physiopathology of OA. Hence, we aimed to review the current literature on the effects of IL-1 and TNF-alpha neutralization as a new OA therapy. In vitro and experimental models showed a reduction in cartilage destruction with IL-1 inhibition therapy by IL-1 receptor antagonists (IL-1Ra). Despite this favorable evidence in animal models, studies on the inhibition of IL-1R in humans are still scarce. Although there is clear evidence that TNF-alpha plays a role in the pathophysiology of OA, only a few experimental trials have investigated the efficacy of blocking this pro-inflammatory cytokine in the treatment of OA. So far, the few studies available in humans using anti-TNF-alpha and IL-1 receptor antagonist are not remarkable, suggesting that further investigation and new therapeutic approaches are needed.
19404929 MicroRNA-124a is a key regulator of proliferation and monocyte chemoattractant protein 1 s 2009 May OBJECTIVE: To elucidate the role of microRNA (miRNA) in the pathogenesis of rheumatoid arthritis (RA), we analyzed synoviocytes from RA patients for their miRNA expression. METHODS: Synoviocytes derived from surgical specimens obtained from RA patients were compared with those obtained from osteoarthritis (OA) patients for their expression of a panel of 156 miRNA with quantitative stem-loop reverse transcription-polymerase chain reaction. The miRNA whose expression decreased or increased in RA synoviocytes as compared with OA synoviocytes were identified, and their target genes were predicted by computer analysis. We used an in vitro system of enhancing the expression of specific miRNA by transfection of precursors into synoviocytes, and then we performed proliferation, cell cycle, and apoptosis assays, as well as enzyme-linked immunosorbent assays for cytokine production. The effects of transfection on predicted target protein and messenger RNA (mRNA) were then examined by Western blot analysis and luciferase reporter assay. RESULTS: We found that miR-124a levels significantly decreased in RA synoviocytes as compared with OA synoviocytes. Transfection of precursor miR-124a into RA synoviocytes significantly suppressed their proliferation and arrested the cell cycle at the G1 phase. We identified a putative consensus site for miR-124a binding in the 3'-untranslated region of cyclin-dependent kinase 2 (CDK-2) and monocyte chemoattractant protein 1 (MCP-1) mRNA. Induction of miR-124a in RA synoviocytes significantly suppressed the production of the CDK-2 and MCP-1 proteins. Luciferase reporter assay demonstrated that miR-124a specifically suppressed the reporter activity driven by the 3'-untranslated regions of CDK-2 and MCP-1 mRNA. CONCLUSION: The results of this study suggest that miR-124a is a key miRNA in the posttranscriptional regulatory mechanisms of RA synoviocytes.
19714611 Evaluation of a novel 7-joint ultrasound score in daily rheumatologic practice: a pilot pr 2009 Sep 15 OBJECTIVE: To introduce a new standardized ultrasound score based on 7 joints of the clinically dominant hand and foot (German US7 score) implemented in daily rheumatologic practice. METHODS: The ultrasound score included the following joints of the clinically dominant hand and foot: wrist, second and third metacarpophalangeal and proximal interphalangeal, and second and fifth metatarsophalangeal joints. Synovitis and synovial/tenosynovial vascularity were scored semiquantitatively (grade 0-3) by gray-scale (GS) and power Doppler (PD) ultrasound. Tenosynovitis and erosions were scored for presence. The scoring range was 0-27 for GS synovitis, 0-39 for PD synovitis, 0-7 for GS tenosynovitis, 0-21 for PD tenosynovitis, and 0-14 for erosions. Patients with arthritis were examined at baseline and after the start or change of disease-modifying antirheumatic drug (DMARD) and/or tumor necrosis factor alpha (TNFalpha) inhibitor therapy 3 and 6 months later. C-reactive protein level, erythrocyte sedimentation rate, rheumatoid factor, anti-cyclic citrullinated peptide, Disease Activity Score in 28 joints (DAS28), and radiographs of the hands and feet were performed. RESULTS: One hundred twenty patients (76% women) with rheumatoid arthritis (91%) and psoriatic arthritis (9%) were enrolled. In 52 cases (43%), erosions were seen in radiography at baseline. Patients received DMARDs (41%), DMARDs plus TNFalpha inhibitors (41%), or TNFalpha inhibitor monotherapy (18%). At baseline, the mean DAS28 was 5.0 and the synovitis scores were 8.1 in GS ultrasound and 3.3 in PD ultrasound. After 6 months of therapy, the DAS28 significantly decreased to 3.6 (Delta = 1.4), and the GS and PD ultrasound scores significantly decreased to 5.5 (-32%) and 2.0 (-39%), respectively. CONCLUSION: The German US7 score is a viable tool for examining patients with arthritis in daily rheumatologic practice because it significantly reflects therapeutic response.
19628821 Effect of rheumatoid factor on mortality and coronary heart disease. 2010 Sep OBJECTIVE: An association between rheumatoid factor (RF) and increased mortality has been described in individuals with rheumatoid arthritis. The objective of this study was to determine the effect of RF on mortality and coronary heart disease (CHD) in the general population. SUBJECTS: were participants in a population-based study focused on cardiovascular disease who attended for a study visit during the years 1974-84. RF was measured and information obtained on cardiovascular risk factors, joint symptoms and erythrocyte sedimentation rate (ESR). The subjects were followed with respect to mortality and incident CHD through 2005. Adjusted comparison of overall survival and CHD event-free survival in RF-positive versus RF-negative subjects was performed using Cox proportional hazards regression models. RESULTS: Of 11 872 subjects, 140 had positive RF. At baseline RF was associated with diabetes mellitus and smoking and inversely associated with serum cholesterol. RF-positive subjects had increased all-cause mortality (HR 1.47, 95% CI 1.19 to 1.80) and cardiovascular mortality (HR 1.57, 95% CI 1.15 to 2.14) after adjusting for age and sex. Further adjustment for cardiovascular risk factors and ESR only modestly attenuated this effect. An increase in CHD among the RF-positive subjects did not reach statistical significance (HR 1.32, 95% CI 0.96 to 1.81, adjusted for age and sex). Subjects with RF but without joint symptoms also had increased overall mortality and cardiovascular mortality (HR for overall mortality 1.33, 95% CI 1.01 to 1.74, after adjustment). CONCLUSION: In a general population cohort, RF was associated with increased all-cause mortality and cardiovascular mortality after adjustment for cardiovascular risk factors, even in subjects without joint symptoms.
20155830 Incidence and mortality of interstitial lung disease in rheumatoid arthritis: a population 2010 Jun OBJECTIVE: Interstitial lung disease (ILD) has been recognized as an important comorbidity in rheumatoid arthritis (RA). We undertook the current study to assess incidence, predictors, and mortality of RA-associated ILD. METHODS: We examined a population-based incidence cohort of patients with RA and a matched cohort of individuals without RA. All subjects were followed up longitudinally. The lifetime risk of ILD was estimated. Cox proportional hazards models were used to compare the incidence of ILD between cohorts, to investigate predictors, and to explore the impact of ILD on survival. RESULTS: Patients with RA (n = 582) and subjects without RA (n = 603) were followed up for a mean of 16.4 and 19.3 years, respectively. The lifetime risk of developing ILD was 7.7% for RA patients and 0.9% for non-RA subjects. This difference translated into a hazard ratio (HR) of 8.96 (95% confidence interval [95% CI] 4.02-19.94). The risk of developing ILD was higher in RA patients who were older at the time of disease onset, in male patients, and in individuals with more severe RA. The risk of death for RA patients with ILD was 3 times higher than in RA patients without ILD (HR 2.86 [95% CI 1.98-4.12]). Median survival after ILD diagnosis was only 2.6 years. ILD contributed approximately 13% to the excess mortality of RA patients when compared with the general population. CONCLUSION: Our results emphasize the increased risk of ILD in patients with RA. The devastating impact of ILD on survival provides evidence that development of better strategies for the treatment of ILD could significantly lower the excess mortality among individuals with RA.
20828280 Golimumab: a new anti-TNF-alpha agent for rheumatoid arthritis, psoriatic arthritis and an 2010 Sep Rheumatoid arthritis (RA) is a chronic inflammatory systemic disease characterized by symmetric arthritis leading to progressive erosion of cartilage and bone. Psoriatic arthritis and ankylosing spondylitis are also inflammatory arthritides that belong to the spondyloarthritides. Disease-modifying anti-rheumatic drugs and biologic therapies including anti-TNF agents are used in their treatment. The TNF antagonists have shown rapid and sustained therapeutic responses. However, a substantial number of patients fail to respond to anti-TNF agents or experience side effects. Golimumab is a human monoclonal antibody to TNF-α requiring less frequent administration compared with current anti-TNF products. Various trials have shown promising results in terms of efficacy and safety in methotrexate-naive and -resistant patients with RA as well as in patients previously treated with other anti-TNF agents. The efficacy of golimumab has also been demonstrated in patients with psoriatic arthritis and ankylosing spondylitis.
19581279 Changes in the rates of joint surgery among patients with rheumatoid arthritis in Californ 2010 May BACKGROUND: Treatment of patients with rheumatoid arthritis (RA) has improved markedly over the past 25 years. OBJECTIVE: To investigate whether rates of joint surgery, a long-term consequence of poorly controlled RA, have changed over this period. METHODS: In this population-based, serial cross-sectional study of patients with RA aged >or=40 years in California, trends in annual rates of total knee arthroplasty, total hip arthroplasty, total ankle arthroplasty or arthrodesis and total wrist arthroplasty or arthrodesis from 1983 to 2007 were examined. RESULTS: Rates of joint surgery peaked in the 1990 s and since have decreased. Among patients aged 40-59 years, rates of knee surgery in 2003-2007 were 19% lower than in 1983-1987 (adjusted rate ratio 0.81; 95% CI 0.74 to 0.87, p<0.0001), while rates of hip surgery in 2003-2007 were 40% lower (p<0.0001). Rates of knee and hip surgery did not decrease in patients aged >or=60 years but increased as observed in the general population. Compared with rates of ankle and wrist surgery in the mid-1980s, rates in the mid-2000s decreased significantly in both age groups. CONCLUSIONS: Rates of joint surgery in RA peaked in the 1990 s and have declined thereafter, suggesting that longterm outcomes of RA are improving.
19962215 Leg ulcer and thigh telangiectasia associated with natural killer cell CD56(-) large granu 2010 Mar Clonal disorders of large granular lymphocytes (LGL) represent a rare spectrum of biologically distinct lymphoproliferative diseases originating either from mature T cells or natural killer cells. Both subtypes can manifest as indolent or aggressive disorders. We report a 77-year-old woman with rheumatoid arthritis, splenomegaly, and neutropenia who developed a painful leg ulcer refractory to treatment and thigh telangiectatic lesions. Because of the association of rheumatoid arthritis, splenomegaly, and nonspecific neutropenia, the diagnosis of Felty syndrome was initially made. Further investigation allowed the diagnosis of a CD56(-) natural killer-cell LGL leukemia and documented skin infiltration by natural killer cells. Cutaneous manifestations of LGL leukemia have been rarely reported. This report of pseudo-Felty syndrome with CD56(-) LGL leukemia, presenting with a leg ulcer and telangiectasia, enhances the role of dermatology in the diagnosis of hematologic neoplasia.
20737467 Regulation of complement by cartilage oligomeric matrix protein allows for a novel molecul 2010 Dec OBJECTIVE: Cartilage oligomeric matrix protein (COMP) is a structural component of cartilage, where it catalyzes collagen fibrillogenesis. Elevated amounts of COMP are found in serum during increased turnover of cartilage associated with active joint disease, such as rheumatoid arthritis (RA) and osteoarthritis (OA). This study was undertaken to investigate the ability of COMP to regulate complement, a capacity that has previously been shown for some other cartilage proteins. METHODS: Regulation of complement by COMP was studied using functional in vitro assays. Inter-actions between complement proteins and COMP were investigated by direct binding assay and electron microscopy. Circulating COMP and COMP-C3b complexes in serum and synovial fluid from RA and OA patients and healthy controls were measured with a novel enzyme-linked immunosorbent assay. RESULTS: We found in vivo evidence of complement activation by released COMP in the general circulation of patients with RA, but not patients with OA. COMP induced activation and deposition of C3b and C9 specifically via the alternative pathway of complement, which was attributable to direct interaction between COMP and properdin. Furthermore, COMP inhibited the classical and the lectin complement pathways due to direct interaction with the stalk region of C1q and mannose-binding lectin, respectively. CONCLUSION: COMP is the first extracellular matrix protein for which an active role in inflammation has been demonstrated in vivo. It can activate one complement pathway at the same time as it has the potential to inhibit another. The net outcome of these interactions is most likely determined by the type of released COMP fragments, which may be disease specific.