Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
16570441 [Clinical observation on treatment of rheumatoid arthritis with cake-separated mild moxibu 2006 Mar OBJECTIVE: To observe the effect-increasing action of cake-separated mild moxibustion on rheumatoid arthritis (RA), and to probe a new method for RA. METHODS: Sixty cases were randomly divided into 2 groups. The control group (n=30) were treated with oral administration of methotrexate (MTX) as basic treatment, and non-steroid anti-inflammatory agents (NSAIDs) according to conditions of the patient. The treatment group (n=30) were treated with the same treatment as the control group, and Fuzi case-separated moxibustion at Guanyuan (CV 4) and Zusanli (ST 36) was added. They were treated for 3 months. RESULTS: After treatment of 3 months, the total effective rate was 83.3% in the treatment group, which was higher than 60.0% in the control group (P < 0.05); there were significant differences before and after treatment in all indexes in the two groups (P < 0.05 or P < 0.01); the ratio of the patients who completely withdrew NSAIDs in the treatment group was significantly higher than that in the control group (P < 0.05); the rate of adverse reaction in the treatment group was significantly lower than that in the control group (P < 0.05). CONCLUSION: Fuzi cake-separated mild moxibustion can increase clinical therapeutic effect on RA and reduce dosage of NSAIDs.
18480575 Clinical and radiological features of Pneumocystis pneumonia in patients with rheumatoid a 2008 OBJECTIVE: To elucidate the clinical and radiological features of Pneumocystis pneumonia (PCP) in patients with rheumatoid arthritis (RA), compared with methotrexate (MTX) pneumonitis in RA and Pneumocystis pneumonia in acquired immunodeficiency syndrome (AIDS). SUBJECTS AND METHODS: Retrospective analysis of 14 PCP cases in RA (RA-PCP), 10 MTX pneumonitis cases in RA (MTX-P) and 11 PCP cases in AIDS (AIDS-PCP) from 9 centers in the Kanto area in the last 6 years. RESULTS: Compared with AIDS-PCP, both RA-PCP and MTX-P developed more rapidly, showing higher serum CRP and lower plasma beta-D-glucan levels, and more severe oxygenation impairment. In most of the RA-PCP cases, a high dose of corticosteroid was administered as adjunctive therapy, resulting in a favorable outcome. The mortality was 14% in RA-PCP, 0% in AIDS-PCP and 0% in MTX-P cases. In RA-PCP patients the CD4 cell count showed only mild suppression, not reaching the predisposing level for PCP in HIV infection, suggesting that there are risk factors for RA-PCP other than immunosuppression. Radiologic analysis revealed some characteristic patterns of each disease. In MTX-P, diffuse homogeneous ground glass opacity (GGO) with sharp demarcation by interlobular septa (type A GGO) was found in 70%, while in AIDS-PCP diffuse, homogeneous or nonhomogeneous GGO without interlobular septal boundaries (type B GGO) was predominant (91%). In RA-PCP, type A GGO was found in 6 cases and type B GGO in 5 cases, showing the complex nature of this disease. CONCLUSION: RA-PCP differed considerably from AIDS-PCP clinically and radiologically. Clinically it occurred without severe immunosuppression, and showed characteristic aspects, with more intense inflammation and less parasite burden. Radiologically it mimicked MTX-P in some cases sharing the conspicuous CT features of MTX-P, rendering the distinction of these two disorders difficult.
17951026 Immunoregulatory properties of vasoactive intestinal peptide in human T cell subsets: impl 2008 Mar Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease whose pathogenesis is not completely understood. Unbalanced Th1/Th2 T-cell polarization has been suggested to play a pathogenetic role and therefore, modulation of T-cell polarization is a potential therapeutic target. Vasoactive intestinal peptide (VIP) is a broadly distributed peptide that exerts anti-inflammatory and immunomodulatory effects, in the collagen-induced arthritis (CIA) murine model of RA, and ex vivo, in synovial cells from RA patients. In the present study, we have found that polyclonal stimulation of peripheral blood lymphocytes (PBL) from RA patients produces higher levels of inflammatory mediators and lower levels of Th1 cytokines than PBL from healthy controls; moreover, VIP has negligible effects on inflammatory mediators and Th1 cytokines produced by PBL from healthy controls but favours Th2 profile and enhanced IL-10 production after stimulation. VIP increases the levels of IL-10 and IL-4 in the supernatant of human CD4(+)CD45RA(+) cells cultured in a non-conditioned or a Th2-conditioned situation. In contrast, VIP does not modify the production of these cytokines in a Th1-conditioned medium. In summary, VIP can differentially modify the functional capacity of human lymphocytes by inducing Th2/Treg differentiation depending on their previous phenotype.
17299844 Work disability in rheumatoid arthritis--development over 15 years and evaluation of predi 2007 Mar OBJECTIVE: To investigate work disability rates over 15 years in an early rheumatoid arthritis (RA) cohort and to evaluate predictive factors during the course of the study. METHODS: All patients with early RA of working age (n = 148) were followed and treated at a team care unit. Mean disease duration at inclusion was 1 year. Work characteristics and disease-related variables were recorded annually. Logistic regression analyses were performed to identify predictors for work disability after 5, 10, and 15 years. RESULTS: Work disability rates were 28%, 35%, 39%, and 44% at study start and after 5, 10, and 15 years, respectively. Forty-seven patients reduced working hours and 34 changed work tasks during the study time. Older age, less education, heavy manual work, and much activity limitation assessed by Health Assessment Questionnaire (HAQ) were predictors of work disability. Demographics and work factors had best predictive value in the early phase, while HAQ was a strong predictor at all points in time. Odds ratios for baseline HAQ, 5 year HAQ, and 10 year HAQ were 6.3, 9.6, and 4.1 for work disability after 5, 10, and 15 years, respectively. CONCLUSION: The prevalence of work disability was 28% at inclusion. After 15 years' followup the prevalence was 44%, which is lower than previously reported. HAQ was the single prognostic factor with strong predictive value throughout the study.
17455718 [Impression cytology in patients with dry eye syndrome and various rheumatic diseases]. 2006 PURPOSE: The aim of this study was to evaluate the cytological changes of bulbar conjunctiva in patients with various rheumatic diseases and dry eye syndrome. MATERIAL AND METHODS: 60 patients with rheumatoid arthritis (RA), systemic scleroderma (SScl), primary Sjbgren syndrome (pSS), systemic lupus erythematosus (SLE) and dry eye syndrome were studied. The ocular examination consisted of Schirmer I, break- up time of tear film (BUT), fluorescein and lissamine green staining and impression cytology of bulbar conjunctiva. RESULTS AND CONCLUSIONS: The morphological alternations of bulbar conjunctiva seen in impression cytology specimens correlated with clinical signs of dry eye syndrome.
16079993 Hand disability and related variables in patients with rheumatoid arthritis. 2006 Apr OBJECTIVE: To carry out a cross-sectional study of patients with rheumatoid arthritis (RA) for hand disability, articular damage and to define their relation with demographic, laboratory and clinical parameters. METHODS: The study included 105 RA patients with a mean age of 49.4 years. Demographic parameters of the patients were recorded. Clinical parameters including disease duration, duration of morning stiffness, pain assessed by visual analog scale, Ritchie Articular Index, grip strength, lateral, tip and three-fingered pinch, and laboratory parameters comprising C-reactive protein, erythrocyte sedimentation rate and rheumatoid factor were evaluated in all patients. The Rheumatoid Arthritis Articular Damage (RAAD) score was used to assess the irreversible articular damage and deformities of the hand. Hand disability was assessed by the special hand disability index of Standford Health Assessment Questionnaire (HAQ). RESULTS: Hand disabilities of various levels were detected in 81% of the patients. Disease duration, grip strength, pinch measurements, clinical and laboratory activity parameters were strongly correlated with hand disability (p<0.01). Hand disability was more related to disease activity parameters than articular damage (p<0.01 and p<0.05, respectively). Grip strength and pinch measurements were the most related parameters with hand disability. The disability scores were significantly higher in female patients (p<0.01). The RAAD score was correlated with disease duration and grip strength (p<0.01). The clinical and laboratory parameters and seropositivity were not correlated with articular damage assessed by RAAD score (p>0.05). CONCLUSION: Our data suggest that grip strength and pinch measurements seem to be the most related variables with hand disability and articular damage. Therefore, grip strength and pinch measurement should be included in the evaluation and follow-up of the patients with RA in hand rehabilitation units.
18351144 [Etanercept (Enbrel)--our experiences]. 2007 Rheumatoid arthritis (RA) is a chronic, systemic disease. Female patients outnumber males in a ratio of 3:1. Cytokines and immune cells networks have been identified as important mediators in the pathogenesis and perpetuation of inflammation in RA. This information has been successfully used into the development of new and significantly more effective treatments, for example anticytokines agents. The goal in managing RA is to achieve remission. We report five patients with RA successfully treated with etanercept.
17121488 Monitoring outcomes of arthritis and longitudinal data collection using patient questionna 2006 Though quantitative data might lead to improved information for clinical decisions, at the present time decisions in routine rheumatology practice generally are based largely on qualitative impressions, rather than on data. Patient questionnaires are readily accessible tools that the rheumatologist can use to go beyond impressions and to institute evidence-based guidelines appropriate to his or her own patient population and practice style. The Health Assessment Questionnaire (HAQ) and its derivatives have been shown to be the best predictors of functional and work disability, costs, joint replacement surgery, and mortality. Such questionnaires are at least as good as joint counts, radiographs, and laboratory tests in predicting these outcomes. Every encounter of a patient with a rheumatologist provides an opportunity to collect data. Based on experience with the Brooklyn Outcomes of Arthritis Registry Database, the author advocates distributing a waiting-room questionnaire to every patient who comes for an office visit. Potential benefits of recording questionnaire-based information include identifying trends or important changes in a patient's pain or physical function, providing a baseline for success with various treatment strategies for conditions of the rheumatologist's own practice, allowing patients an opportunity to express concerns, encouraging patients to disclose information they may feel is too minor to mention, and providing control data for research studies. A short questionnaire designed specifically for clinical, rather than research, use does not create a burden for office staff. Consistent use of patient questionnaires and systematic storage of the information gained can help document, track, and improve patient care in routine rheumatology practice.
18163481 Estimates of the prevalence of arthritis and other rheumatic conditions in the United Stat 2008 Jan OBJECTIVE: To provide a single source for the best available estimates of the US prevalence of and number of individuals affected by arthritis overall, rheumatoid arthritis, juvenile arthritis, the spondylarthritides, systemic lupus erythematosus, systemic sclerosis, and Sjögren's syndrome. A companion article (part II) addresses additional conditions. METHODS: The National Arthritis Data Workgroup reviewed published analyses from available national surveys, such as the National Health and Nutrition Examination Survey and the National Health Interview Survey (NHIS). For analysis of overall arthritis, we used the NHIS. Because data based on national population samples are unavailable for most specific rheumatic conditions, we derived estimates from published studies of smaller, defined populations. For specific conditions, the best available prevalence estimates were applied to the corresponding 2005 US population estimates from the Census Bureau, to estimate the number affected with each condition. RESULTS: More than 21% of US adults (46.4 million persons) were found to have self-reported doctor-diagnosed arthritis. We estimated that rheumatoid arthritis affects 1.3 million adults (down from the estimate of 2.1 million for 1995), juvenile arthritis affects 294,000 children, spondylarthritides affect from 0.6 million to 2.4 million adults, systemic lupus erythematosus affects from 161,000 to 322,000 adults, systemic sclerosis affects 49,000 adults, and primary Sjögren's syndrome affects from 0.4 million to 3.1 million adults. CONCLUSION: Arthritis and other rheumatic conditions continue to be a large and growing public health problem. Estimates for many specific rheumatic conditions rely on a few, small studies of uncertain generalizability to the US population. This report provides the best available prevalence estimates for the US, but for most specific conditions, more studies generalizable to the US or addressing understudied populations are needed.
16999275 [Rheumatic diseases as risk factors for cardiovascular disease]. 2006 Sep 2 Cardiovascular disease is the leading cause of death in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and systemic lupus erythematosus (SLE). In addition to mortality, cardiovascular morbidity is also markedly increased in these patients, compared with the general population. The increased cardiovascular risk can be explained only partially by an increased prevalence of classical risk factors for cardiovascular disease; it also appears to be related to inflammation. Prospective intervention trials aimed at the modification of cardiovascular risk factors are needed to determine the impact of cardiovascular risk reduction in patients with rheumatic disease. In addition to SLE, RA and AS should be acknowledged as new risk factors for cardiovascular disease.
17417995 Switching to etanercept in patients with rheumatoid arthritis with no response to inflixim 2007 Jan TNF-alpha is thought to play a pivotal role in the initiation and perpetuation of the chronic inflammatory process in rheumatoid arthritis. TNF-alpha blockers such as infliximab and etanercept are currently used in the treatment of active rheumatoid arthritis (RA) when traditional DMARDs have failed and are effective in a significant proportion of patients. However, about one third are non-responders to anti-TNF-alpha. The aim of this study was to verify whether rheumatoid patients, after failing infliximab, can benefit from etanercept. We analysed 18 patients with active RA with no response to at least 3 DMARDs and where infliximab therapy had failed. The patients had received infliximab associated with methotrexate: eleven of them did not show any significant response, while seven patients, after a good response, relapsed. Etanercept was then started. EULAR criteria of response were used with calculation of activity index DAS28 at baseline, after 2 weeks, 3 months and every third month until last follow-up. A moderate or good response was achieved with etanercept in 13 out of 18 patients. From our experience, etanercept can be considered as a good alternative choice when infliximab has failed.
18058203 Exposure-response modeling using latent variables for the efficacy of a JAK3 inhibitor adm 2008 Apr Currently, no general methods have been developed to relate pharmacologically based models, such as indirect response models, to discrete or ordered categorical data. We propose the use of an unobservable latent variable (LV), through which indirect response models can be linked with drug exposure. The resulting indirect latent variable response model (ILVRM) is demonstrated using a case study of a JAK3 inhibitor, which was administered to patients in a rheumatoid arthritis (RA) study. The clinical endpoint for signs and symptoms in RA is the American College of Rheumatology response criterion of 20%--a binary response variable. In this case study, four exposure-response models, which have different pharmacological interpretations, were constructed and fitted using the ILVRM method. Specifically, two indirect response models, an effect compartment model, and a model which assumes instantaneous (direct) drug action were assessed and compared for their ability to predict the response data. In general, different model interpretations can influence drug inference, such as time to drug effect onset, as well as affect extrapolations of responses to untested experimental conditions, and the underlying pharmacology that operates to generate key response features does not change because the response was measured discretely. Consideration of these model interpretations can impact future study designs and ultimately provide greater insight into drug development strategies.
18672035 Anti-inflammatory effects of leaf and twig of Tripterygium wilfordii on paw edema in mice. 2008 Dec The root of Tripterygium wilfordii (TWH) is a traditional Chinese herb used to treat the immune-related diseases such as rheumatoid arthritis, whereas the leaf and twig of TWH was considered useless and discarded. We performed a study on the anti-inflammatory effects on the leaf and twig portion agent using carrageenan- and adjuvant-induced paw edema in rats. They showed a marked inhibitory effect on edema in both models of inflammation in rats, at the dose of 50, 100 and 200 mg/kg, especially on secondary immunological arthritis. Based on this study, we confirmed that the leaf and twig of TWH is a potentially useful drug suitable for further evaluation for rheumatoid arthritis and can replace root of TWH.
18504526 A case with life-threatening interstitial pneumonia associated with bucillamine treatment. 2008 We report a case of bucillamine-induced interstitial pneumonia accompanied by severe hypoxemia in an 83-year-old woman who had rheumatoid arthritis. Respiratory failure worsened even after withdrawal of bucillamine and administration of high-dose corticosteroids, and mechanical ventilation was required. A review of 15 cases with bucillamine-induced pulmonary injury suggests that advanced age may be associated with the development of severe interstitial pneumonia. Bucillamine can cause corticosteroid-resistant and life-threatening lung injury, especially in the elderly.
18684973 Annexin-1 mediates TNF-alpha-stimulated matrix metalloproteinase secretion from rheumatoid 2008 Aug 15 Annexins are intracellular molecules implicated in the down-regulation of inflammation. Recently, annexin-1 has also been identified as a secreted molecule, suggesting it may have more complex effects on inflammation than previously appreciated. We studied the role of annexin-1 in mediating MMP-1 secretion from rheumatoid arthritis (RA) synovial fibroblasts (SF) stimulated with TNF-alpha. TNF-alpha induced a biphasic secretion of annexin-1 from RA SF. Early (< or = 60 min), cycloheximide-independent secretion from preformed intracellular pools was followed by late (24 h) cycloheximide-inhibitable secretion requiring new protein synthesis. Exogenous annexin-1 N-terminal peptide Ac2-26 stimulated MMP-1 secretion in a dose- (EC(50) approximately 25 microM) and time- (8-24 h) dependent manner; full-length annexin-1 had a similar effect. Down-regulation of annexin-1 using small interfering RNA resulted in decreased secretion of both annexin-1 and MMP-1, confirming that annexin-1 mediates TNF-alpha-stimulated MMP-1 secretion. Erk, Jnk, and NF-kappaB have been implicated in MMP-1 secretion. Erk, Jnk, and NF-kappaB inhibitors had no effect on annexin-1 secretion stimulated by TNF-alpha but inhibited MMP-1 secretion in response to Ac2-26, indicating that these molecules signal downstream of annexin-1. Annexin-1 stimulation of MMP-1 secretion was inhibited by both a formyl peptide receptor antagonist and pertussis toxin, suggesting that secreted annexin-1 acts via formyl peptide family receptors, most likely FPLR-1. In contrast to its commonly appreciated anti-inflammatory roles, our data indicate that annexin-1 is secreted by RA SF in response to TNF-alpha and acts in an autacoid manner to engage FPRL-1, activate Erk, Jnk, and NF-kappaB, and stimulate MMP-1 secretion.
18853156 Reinfusion of unwashed salvaged blood after total knee arthroplasty in patients with rheum 2009 Dec Autotransfusion with unwashed salvaged blood (USB) is effective for avoiding allogeneic blood transfusion (ABT) in patients undergoing total knee arthroplasty (TKA). We performed a retrospective study to determine the percentage of patients receiving ABT and the volume of postoperative blood drainage after introduction of autotransfusion with USB for patients with rheumatoid arthritis (RA) undergoing TKA. In 100 patients without autotransfusion (group 1) and 100 patients receiving autotransfusion of USB (group 2), we compared the number of patients who required ABT, as well as the postoperative drainage volume, ABT volume, and autotransfusion volume. In group 1, 83% of the patients received ABT, while only 47% received ABT in group 2, and there was a significant decrease (p < 0.001). However, the postoperative drainage volume was significantly increased in group 2 (p < 0.001).
17665439 Fractalkine is a novel chemoattractant for rheumatoid arthritis fibroblast-like synoviocyt 2007 Aug OBJECTIVE: Fibroblast-like synoviocytes (FLS) are a major constituent of the hyperplastic synovial pannus that aggressively invades cartilage and bone during the course of rheumatoid arthritis (RA). Fractalkine (FKN/CX(3)CL1) expression is up-regulated in RA synovium and RA synovial fluid. While RA FLS express the FKN receptor, CX(3)CR1, the pathophysiologic relevance of FKN stimulation of RA FLS is not understood. This study was undertaken to better characterize the relationship between FKN and the RA FLS that both produce it and express its receptor. METHODS: RA FLS were subjected to chemotaxis and proliferation assays, Western blotting, enzyme-linked immunosorbent assays, and filamentous actin staining to characterize the relationship between FKN and RA FLS. RESULTS: FKN secretion by RA FLS was regulated mainly by tumor necrosis factor alpha. Stimulation of RA FLS with FKN led to significant cytoskeletal rearrangement but no proliferation. Chemotaxis assays revealed that FKN was a novel chemoattractant for RA FLS. Stimulation of RA FLS with FKN resulted in activation of MAP kinases and Akt. JNK, ERK-1/2, and Akt (at both Ser-473 and Thr-308) were each up-regulated in a time-dependent manner. Inhibition of ERK-1/2-mediated signaling, but not JNK or Akt, significantly repressed FKN-induced RA FLS migration. CONCLUSION: These findings indicate a novel role of FKN in regulating RA FLS cytoskeletal structure and migration. FKN specifically induces RA FLS phosphorylation of the MAP kinases JNK and ERK-1/2, as well as full activation of Akt.
18625628 Responsiveness of the International Classification of Functioning, Disability and Health ( 2009 Jun BACKGROUND: The comprehensive International Classification of Functioning, Disability and Health (ICF) Core Set for rheumatoid arthritis (RA) is a selection of 96 categories from the ICF, representing relevant aspects in the functioning of patients with RA. OBJECTIVES: To study the responsiveness of the ICF Core Set for RA in rheumatological practice. METHODS: A total of 46 patients with RA (72% women, mean (SD) age 53.6 (12.6) years, disease duration 6.3 (8.0) years) were interviewed at baseline and again after 6 months treatment with a disease-modifying antirheumatic drug (DMARD), applying the ICF Core Set for RA with qualifiers for problems on a modified three-point scale (no problem, mild/moderate, severe/complete). Patient-reported outcomes included Modified Health Assessment Questionnaire (MHAQ) and Short-Form 36 (SF-36) health survey, and disease activity was calculated. Responsiveness was measured as change in qualifiers in ICF categories, and was also compared with change in patient-reported outcomes. RESULTS: After 6 months of DMARD treatment, improvement by at least one qualifier was seen in 20% of patients (averaged across all ICF categories), 71% experienced no change and 9% experienced worsening symptoms. Findings were similar across the different aspects of functioning. Mainly moderate effect sizes were seen for 6-month changes in the ICF Core Set for RA, especially in patients with improved health status, with similar effect size for disease activity. The components in the ICF Core Set for RA were only weakly associated with patient-reported outcomes and disease activity. CONCLUSIONS: The ICF Core Set for RA demonstrated moderate responsiveness in this real-life setting of patients where minor changes occurred during treatment with DMARDs.
16788406 Subacromial space measurement: a reliable method indicating fatty infiltration in patients 2006 Oct Proximal migration of the humeral head is thought to indicate fatty infiltration of the rotator cuff muscles or rotator cuff tears. We sought to evaluate the influence of these rotator cuff abnormalities on the subacromial space. Using anteroposterior radiographs, ultrasound, and computed tomography, we analyzed 54 shoulders in 29 patients with rheumatoid arthritis. The upward migration index was defined as proximal migration of the humeral head relative to its size. The mean muscle density from computed tomography images was used to indicate fatty infiltration. Fatty infiltration of the infraspinatus muscle showed the strongest correlation with proximal migration. After correcting for age, cuff tears, and rheumatoid disease, the partial correlation coefficient between both remained strong. A subdivision in proximal migration is proposed to screen for rotator cuff abnormalities. A large amount of fatty infiltration was indicated by an upward migration index less than 1.25, a medium amount by an upward migration index between 1.25 to 1.35, and a small amount by an upward migration index greater than 1.35. Measurement of proximal migration using the upward migration index provides a reliable screening method indicating fatty infiltration of the rotator cuff.
17015143 Antiphospholipid antibodies as a possible risk factor for atherosclerosis in patients with 2006 Atherosclerosis shares many similarities with inflammatory and autoimmune diseases, among them rheumatoid arthritis (RA). Anticardiolipin antibodies (aCL) and antibodies against beta2-glycoprotein I (anti-beta2GPI) have been detected in sera of RA patients in several studies. We demonstrated aCL and anti-beta2GPI in a selected group of 70 patients with RA (premenopausal women, non-diabetic, non-hypertensive) and compared them with age- and sex-matched controls. There was a significant higher internal carotid artery intima-media thickness and number of plaques in RA patients compared to controls. aCL of IgG and IgM classes were present in 15.7% of RA patients as compared to 5% in the control group. Thirty percent of RA patients had anti-beta2GPI of IgG, IgM and IgA classes compared to 7.5% in controls. Major differences were seen in IgG and IgA classes. Our results support the idea that aCL and anti-beta2GPI represent an important risk factor for atherosclerosis in RA patients. Elevated levels of phosphatidylserine-dependent antiprothrombin antibodies did not contribute significantly to the general prevalence of antiphospholipid antibodies.