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ID PMID Title PublicationDate abstract
17265489 Amelioration of collagen-induced arthritis in rats by nanogold. 2007 Feb OBJECTIVE: Angiogenesis plays a part in the pathogenesis of rheumatoid arthritis (RA), and nanogold inhibits the activity of an angiogenic factor, vascular endothelial growth factor (VEGF). We therefore investigated whether intraarticular delivery of nanogold ameliorates collagen-induced arthritis (CIA) in rats. METHODS: Binding of 13-nm nanogold to VEGF in human RA synovial fluid (SF) and its effects on RA SF-induced endothelial cell proliferation and migration were assessed. Nanogold was administered intraarticularly to rats with CIA before the onset of arthritis. Progression of CIA was monitored by measures of clinical, radiologic, and histologic changes. In addition, the microvessel density and extent of infiltrating macrophages as well as levels of tumor necrosis factor alpha (TNFalpha) and interleukin-1beta (IL-1beta) in the ankle joints were determined. RESULTS: Nanogold bound to VEGF in RA SF, resulting in inhibition of RA SF-induced endothelial cell proliferation and migration. Significant reductions in ankle circumference, articular index scores, and radiographic scores were observed in the nanogold-treated rats with CIA compared with their control counterparts. In addition, the histologic score (of synovial hyperplasia, cartilage erosion, and leukocyte infiltration), microvessel density, macrophage infiltration, and levels of TNFalpha and IL-1beta were also significantly reduced in the ankle joints of nanogold-treated rats. CONCLUSION: Our results are the first to demonstrate that intraarticular administration of nanogold ameliorates the clinical course of CIA in rats. Nanogold exerted antiangiogenic activities and subsequently reduced macrophage infiltration and inflammation, which resulted in attenuation of arthritis. These results demonstrate proof of principle for the use of nanogold as a novel therapeutic agent for the treatment of RA.
17414948 Glucocorticoids: action and new therapeutic insights in rheumatoid arthritis. 2007 May PURPOSE OF REVIEW: To summarize the mechanism of action of glucocorticoids, the direction that current research is taking and what this might mean for clinicians. RECENT FINDINGS: New cellular actions of glucocorticoids have been identified, and offer new drug targets. There is increasing competition to find a glucocorticoid formulation or analogue that enhances therapeutic effects while reducing adverse effects. Clinically, there is increasing evidence for the disease-modifying effects of glucocorticoids, which makes these developments topical and relevant. Better understanding of the pathology of rheumatoid arthritis and the circadian variation in symptoms that is a hallmark of the disease may also affect the way that we use these drugs. SUMMARY: Glucocorticoids are about to enter a renaissance based on better understanding of how they work and novel approaches to new therapeutic targets.
16465650 Magnetic resonance imaging quantification of hand synovitis in patients with rheumatoid ar 2006 Feb OBJECTIVE: To investigate the clinical response and to evaluate by magnetic resonance imaging (MRI) the inflammatory tissue changes in patients with refractory rheumatoid arthritis (RA) treated with adalimumab. METHODS: Thirteen patients with refractory RA who were treated with adalimumab (40 mg every 2 weeks subcutaneously) were examined with MRI of the dominant affected wrist and hand before treatment and one year after therapy. The volume of the enhanced inflammatory tissue (VEIT) was evaluated in fat-suppressed contrast-enhanced T1-weighted MRI images using the Analyse 4.0 software. Disease activity was evaluated using the Disease Activity Score 28-joint (DAS-28). Clinical improvement was evaluated according to the American College of Rheumatology 20% response criteria (ACR20%). RESULTS: We studied 12 women and one man, with mean age 52.0 +/- 10.9 years and mean disease duration 13.0 +/- 8.5 years. Eight patients had positive IgM rheumatoid factor. One year after treatment, 11 (84.6%) patients showed a decrease of the VEIT. Moreover the values of C-reactive protein (CRP; 4.3 +/- 6.6 mg/l), the erythrocyte sedimentation rate (ESR; 26.3 +/- 19.5 mm/h), the DAS-28 (3.5 +/- 1.1), and the VEIT (21.6 +/- 10.7 cm3) after treatment were significantly lower compared to the corresponding values before treatment (CRP 41.6 +/- 39.2), (ESR 54.3 +/- 28.6) (DAS-28 5.8 +/- 0.8), and (VEIT 36.9 +/- 16.8) (p < 0.01). All but 3 (76.9%) patients with RA achieved the ACR20% response, while 7 (53.8%) and 5 (38.5%) patients achieved ACR50% and ACR70% response, respectively. A positive correlation between VEIT, swollen joint count, and ESR was found before treatment (r = 0.59, r = 0.64, respectively; p < 0.05). CONCLUSION: In patients with refractory RA, treatment with adalimumab resulted in improvement of clinical, laboratory, and MRI findings. MRI assessment of the VEIT may represent an additional tool for investigation of joint disease activity and responsiveness to treatment.
18828865 Altered lipoprotein metabolism in chronic inflammatory states: proinflammatory high-densit 2008 In this review, the authors discuss the formation and structure of high-density lipoproteins (HDLs) and how those particles are altered in inflammatory or stress states to lose their capacity for reverse cholesterol transport and for antioxidant activity. In addition, abnormal HDLs can become proinflammatory (piHDLs) and actually contribute to oxidative damage. The assay by which piHDLs are identified involves studying the ability of test HDLs to prevent oxidation of low-density lipoproteins. Finally, the authors discuss the potential role of piHDLs (found in some 45% of patients with systemic lupus erythematosus and 20% of patients with rheumatoid arthritis) in the accelerated atherosclerosis associated with some chronic rheumatic diseases.
17552045 Health status disparities in ethnic minority patients with rheumatoid arthritis: a cross-s 2007 Jul OBJECTIVE: To examine disparities in disability, pain, and global health between Caucasian (n = 4294) and African American (n = 283) and Caucasian and Hispanic (n = 153) patients with rheumatoid arthritis (RA). METHODS: Patients were from 9 Arthritis, Rheumatism, and Aging Medical Information System databanks. Cross-sectional data were derived from the Health Assessment Questionnaire. Staged multivariate analysis of covariance was used to explore roles of possible contributing factors (age, sex, education, disease duration, number of comorbid conditions, and treatment) to ethnic minority disparities. RESULTS: The cohort was 91% Caucasian and 76% female. Caucasians were significantly older than African Americans and Hispanics (62 vs 56 and 55 yrs; both p < 0.0001 from Caucasians), better educated (13 vs 12 and 12 yrs; both p < 0.0001 from Caucasians), and had their RA longer (16 vs 13 and 15 yrs; p < 0.01 for African Americans). Unadjusted disability scores were statistically indistinguishable, but pain was worse in both ethnic groups (p < 0.01), and global health worse in Hispanics (p < 0.05). After adjustment for covariates, African Americans had the poorest outcomes in all 3 measures, although only pain in African Americans (p < 0.05) was statistically different from Caucasians. CONCLUSION: Results of this exploratory study suggest that in a relatively similar cohort of patients with RA, minority health disparities exist. Both ethnic groups had poorer outcomes for all 3 measures than Caucasians after adjustment. Additional study and longitudinal research with larger numbers of patients are needed to improve our understanding of these differences and to assess potential causal roles.
17144587 [A case of rheumatoid lung complicated by SELAPINA-induced pneumonia]. 2006 Nov SELAPINA is generic product of PL granule which is one of the most common forms of combination remedies for the common cold in Japan, and includes acetaminophen. We report a case of SELAPINA-induced pneumonia successfully treated with glucocorticoid pulse therapy followed by orally administered prednisolone. A 68-year-old woman, who had been treated for rheumatoid arthiritis with pulmonary involvement, took SELAPINA with an antibiotic for 6 days because of her cold symptoms. She then suffered a high fever, cough, dyspnea, vomiting and diarrhea. Chest radiograph and high-resolution computed tomography (HRCT) scan revealed diffuse interstitial shadows. SELAPINA-induced pneumonia was diagnosed because the blastoid transformation test using her peripheral blood lymphocytes was positive on stimulation with SELAPINA, but negative for other medicines.
19106168 Transforming growth factor-beta1 869T/C, but not interleukin-6 -174G/C, polymorphism assoc 2009 Feb OBJECTIVES: Part of the deleterious effects of systemic inflammation on the cardiovascular system of patients with RA may be exerted via increased propensity to hypertension. IL-6 and TGF-beta1 are important regulators of the inflammatory response. In some, but not all, studies, IL6 -174G/C (rs1800795) and TGFB1 869T/C (rs1982073) gene polymorphisms have been associated with hypertension in the general population. The present study addressed their potential association with hypertension in RA patients. METHODS: TGFB1 869T/C and IL6 -174G/C were identified in 400 RA patients and 422 local, non-RA controls using real-time PCR and melting curve analysis. Binary logistic and linear regression models were used to identify the independence of the effects of the polymorphisms on hypertension. RESULTS: Genotypic and allelic frequencies of the two polymorphisms were similar in RA and controls. Within the RA group, there was no significant association between IL6 -174G/C and hypertension, but TGF 869T-allele carriers had significantly increased prevalence of hypertension compared with CC homozygotes (70.2 vs 55.2%; P = 0.023). This association remained significant after adjustment for other hypertension risk factors and medication (odds ratio = 1.96; 95% CI 1.02, 3.77; P = 0.044), and was more pronounced in patients with increased systemic inflammation. CONCLUSIONS: This study suggests an association of TGFB1 869T/C, but not of IL6 -174G/C, with hypertension in RA patients. If this finding is confirmed in prospective studies, this polymorphism could be used as a screening tool for RA patients with higher risk of developing hypertension and lead to increased surveillance and earlier treatment.
17255475 Cadherin-11 in synovial lining formation and pathology in arthritis. 2007 Feb 16 The normal synovium forms a membrane at the edges of joints and provides lubrication and nutrients for the cartilage. In rheumatoid arthritis, the synovium is the site of inflammation, and it participates in an organized tissue response that damages cartilage and bone. We identified cadherin-11 as essential for the development of the synovium. Cadherin-11-deficient mice have a hypoplastic synovial lining, display a disorganized synovial reaction to inflammation, and are resistant to inflammatory arthritis. Cadherin-11 therapeutics prevent and reduce arthritis in mouse models. Thus, synovial cadherin-11 determines the behavior of synovial cells in their proinflammatory and destructive tissue response in inflammatory arthritis.
17629805 Effect of low level laser therapy in rheumatoid arthritis patients with carpal tunnel synd 2007 Jun 16 OBJECTIVE: the aim of the present study was to evaluate the efficacy of low level laser therapy (LLLT) in patients with rheumatoid arthritis (RA) with carpal tunnel syndrome (CTS). MATERIAL AND METHODS: a total of 19 patients with the diagnosis of CTS in 19 hands were included and randomly assigned to two treatment groups; LLLT (Group 1) (10 hands) with dosage 1.5 J/ per point and placebo laser therapy group (Group 2) (9 hands). A Galium-Aluminum-Arsenide diode laser device was used as a source of low power laser with a power output of 50 mW and wavelength of 780 nm. All treatments were applied once a day on week days for a total period of 10 days. Clinical assessments were performed at baseline, at the end of the treatment and at month 3. Tinel and Phalen signs were tested in all patients. Patients were evaluated for such clinical parameters as functional status scale (FSS), visual analogue scale (VAS), symptom severity scale (SSS) and grip-strength. However, electrophysiological examination was performed on all hands. Results were given with descriptive statistics and confidence intervals between group means at 3 months adjusted for outcome at baseline and for the difference between unadjusted group proportions. RESULTS: clinical and electrophysiological parameters were similar at baseline in both groups. Improvements were significantly more pronounced in the LLLT group than placebo group. A comparison between groups showed significant improvements in pain score and functional status scale score. Group mean differences at 3 months adjusted at baseline were found to be statistically significant for pain score and functional status scale score. The 95% significant confidence intervals were [-15 - (-5)] and [-5 - (-2)] respectively. There were no statistically significant differences in other clinical and electrophysiological parameters between groups at 3 months. CONCLUSIONS: our study results indicate that LLLT and placebo laser therapy seems to be effective for pain and hand function in CTS. We, therefore, suggest that LLLT may be used as a good alternative treatment method in CTS patients with RA.
17947301 Probability of continued low disease activity in patients with recent onset rheumatoid art 2008 Feb OBJECTIVE: To assess the duration and the probability of maintaining low disease activity once a low disease activity score (DAS) is achieved in recent onset rheumatoid arthritis (RA) patients. METHODS: The BeSt study is a randomised trial comparing four different treatment strategies in patients with recent onset, active RA. Treatment adjustments were mandatory as long as the DAS was >2.4. If the DAS was
16936332 Time use patterns among women with rheumatoid arthritis: association with functional limit 2007 Mar OBJECTIVES: This study assessed time use patterns among 375 women with rheumatoid arthritis (RA). We hypothesized that (i) as functional limitations increased, time use imbalances would occur (i.e. time needed for obligatory activities would conflict with time needed for productive and free-time activities) and (ii) time use imbalances would be associated with psychological distress. METHODS: Time use estimates were obtained from written questionnaires; other study data were collected from annual telephone interviews. Activities were categorized as obligatory, committed or discretionary, as defined by Verbrugge. Time use estimates were aggregated to define number of obligatory (e.g. self-care) activities requiring >2 h/day and a number of committed and discretionary activities in which no time was spent each day. RESULTS: After adjusting for age, education, marital status and pain severity, women with more functional limitations were significantly more likely to spend >2 h/day in obligatory activities. As functional limitations increased, the proportion spending no time in each committed activity and many discretionary activities increased. Spending >2 h/day in obligatory activities was not significantly associated with poor psychological status, but spending no time in a greater number of committed and discretionary activities was associated with lower life satisfaction and higher levels of depressive symptoms. CONCLUSIONS: Having more severe functional limitations appears to shift time use patterns towards more time spent in obligatory activities and less time spent in committed and discretionary activities. These imbalances in time use were associated with psychological distress, highlighting the need for women with RA to maintain important productive, social and discretionary activities.
17169851 Rheumatoid arthritis is a risk factor for dry eye in the Indian population. 2006 Dec PURPOSE: To compare the prevalence and severity of dry eye in patients with rheumatoid arthritis (RA) with that in age- and sex-matched controls in the Indian population. METHODS: A cross-sectional study was performed on 84 randomly selected eyes of 84 adult patients with well-documented rheumatoid arthritis and 84 eyes of 84 age- and sex-matched controls in the Department of Ophthalmology, Seth G.S. Medical College and K.E.M. Hospital. McMonnie's dry eye questionnaire was used to classify the patients on the basis of their symptoms. Dry eye was diagnosed if the wetting on Schirmer filter paper test was < or =5 mm at 5 minutes and the tear film breakup time was < 10 seconds on slit-lamp examination after fluorescein staining. RESULTS: Twenty three patients (27.3%) with rheumatoid arthritis had dry eyes based on the Schirmer test as compared to 10 (12%) age- and sex-matched controls; 19 (22.62%) patients with RA had a tear film breakup time of < 10 sec. on slit-lamp examination, compared to 8 (9.52%) patients without RA. The difference in the mean wetting (p = 0.003) and mean tear film breakup time (p < 0.001) between RA and non-RA patients was statistically significant. Ocular symptoms had a limited correlation with the results of these tests. CONCLUSIONS: Patients with RA in the Indian population have a significantly higher prevalence and severity of dry eye when compared to age- and sex-matched controls.
16610380 An unusual rupture of the flexor carpi radialis tendon: a case report. 2006 Mar We present the unusual case of a flexor carpi radialis tendon that ruptured after extended strenuous physical activity by a patient with paralysis of the opposite limb secondary to poliomyelitis.
18039720 Monitoring rheumatoid arthritis synovitis with 99mTc-anti-CD3. 2008 Jan The aim of this study was to investigate the feasibility of using a monoclonal antibody (OKT3) labelled with technetium-99m (99mTc) to monitor disease activity in patients with rheumatoid arthritis. We evaluated 38 patients who were diagnosed with rheumatoid arthritis and classified as Classes II and III after functional assessment (according to the revised criteria specified by the American College of Rheumatology). Two sets of planar anterior images of the patients' wrists, metacarpophalangeal and interphalangeal joints, elbows, shoulders and knees joints were obtained 1 h and 3 h after the injection of 99mTc-OKT3. The scintigraphic findings showed significant correlation (p<0.05) between the radiopharmaceutical accumulation of 99mTc-OKT3 and swollen joints, tender joints and the visual analogue scale. They were able to differentiate patients in remission from patients with active synovitis, according to DAS 28. In contrast, there was no correlation between the radiopharmaceutical accumulation and the patients' age, gender, duration of disease or erythrocyte sedimentation rate. A relatively high disease activity score of 28 joints (4.08+/-1.74) was found in the majority of patients. In conclusion, 99mTc-OKT3 scintigraphy is a reliable and objective method for detecting synovial activity, and can be used to observe disease prognosis.
16855157 Oral pulsed dexamethasone therapy in early rheumatoid arthritis: a pilot study. 2006 Jun Pulse therapy with high-dose glucocorticoids (GCs) is widely used as "bridging therapy" for the treatment of patients with active rheumatoid arthritis (RA). Oral pulsed dexamethasone therapy has never been used for this purpose. We determined the clinical efficacy of oral pulsed dexamethasone treatment in patients with early active RA, concomitantly starting with disease-modifying anti-rheumatic drugs (DMARDs). Fourteen early RA patients, glucocorticoid-naive and with active disease for less than 1 year were included. Ten patients were treated with oral pulsed dexamethasone therapy for 4 days in a row. Of this group, four patients received 10 mg dexamethasone/day, three patients 20 mg/day, and three patients 40 mg/day. As controls, four patients were treated with intramuscular methylprednisolone injections. Disease activity (ascertained by disease activity score [DAS]) and biochemical variables were measured at base line, and biweekly thereafter for up to 4 weeks, and monthly thereafter for up to 3 months. A decrease in disease activity, similar in all subgroups, was observed. Nine of 10 patients responded favorably (decrease in DAS of >1.2) 4 weeks after the start of the study. This response was sustained in the months thereafter. One patient did not respond at all, and disease progression during treatment was observed in one patient. No side effects were reported. Only once was a decrease in cortisol level observed; this was at 2 weeks after the start of the study (0.03 micromol/L, reference value 0.18-0.70 micromol/L). Oral pulsed dexamethasone therapy seems to be effective and safe as bridging therapy in early rheumatoid arthritis. The results of the present study justify a long-term controlled trial to compare oral pulsed dexamethasone treatment (10 mg dexamethasone, once weekly for 4 weeks) with the standard GC regimes in the near future.
18642727 Characterization of immunogenic properties of polyclonal T cell vaccine intended for the t 2007 Oct Two-staged technology for obtaining polyclonal T cell vaccine intended for the treatment of rheumatoid arthritis is described. Stage 1 includes antigen-dependent cultural selection of patient's T cells and stage 2 consists in their reproduction in the needed amounts by nonspecific mitogenic stimulation. T cell vaccination induces an effective specific anti-idiotypic immune response against T cells reactive to joint antigens. Vaccine therapy significantly reduces plasma level of IFN-gamma and increases IL-4 level. The results indicate immunological efficiency and safety of polyclonal T cell vaccine in patients with rheumatoid arthritis.
16467036 Lack of association of the CD14/C-159T polymorphism with susceptibility and serological ac 2006 Jan OBJECTIVE: CD14, the monocyte receptor for lipopolysaccharides (LPS), is an important mediator of inflammatory processes. As the T-159C exchange in the promotor of the CD14 gene was reported to lead to enhanced CD14 expression, this could be a new susceptibility gene for rheumatoid arthritis (RA). We investigated whether this single nucleotide polymorphism (SNP) serves as a risk factor for disease development or has any influence on serological activity parameters of RA or soluble CD14 (sCD14) levels. PATIENTS AND METHODS: A total of 130 patients with RA, diagnosed according to the revised American College of Rheumatology (ACR) criteria, and 130 healthy subjects, all Caucasians, were genotyped using polymerase chain reaction (PCR). Genotype frequencies were compared by chi2 analysis. RESULTS: Forty (31%) patients vs. 39 (30%) controls were genotyped CC; 71 (55%) vs. 67 (52%) were heterozygous, and 19 (15%) vs. 24 (19%) showed the TT genotype (p = 0.7). Accordingly, the allele frequency was equally distributed (p = 0.8). There was also no significant difference in genotype distribution between subgroups of patients categorized according to serological activity parameters and sCD14 levels. CONCLUSION: We found no association between the CD14/C-159T polymorphism and increased risk for the development of RA or serological disease activity parameters or sCD14 levels.
18807544 [Simvastatin effects on the disease activity and cholesterol content in blood serum lipopr 2008 AIM: To study activity of rheumatoid arthritis (RA) and cholesterol content in subfractions of blood serum lipoproteins in the course of simvastatin treatment. MATERIAL AND METHODS: The pilot study enrolled 16 patients with active rheumatoid arthritis (RA) meeting ACR criteria. Any standard anti-RA medication in stable doses was supplemented with simvastatin in a dose 40 mg/day for 12 weeks. The response was assessed by contents of cholesterol in serum lipoprotein subfractions and DAS28 index. RESULTS: At the end of the treatment course there was a significant elevation of HDLP2 and HDLP3 cholesterol and reduction in the levels of LDLP1-3 and LDLP cholesterol. DAS28 decreased by 0.89 points to the end of the treatment. CONCLUSION: Administration of simvastatin in patients with active RA on standard disease-modulating drugs has an antiatherogenic action and attenuates the disease activity. These pilot data should be confirmed by further large-scale controlled trials.
18839010 Molecular effects of exercise in patients with inflammatory rheumatic disease. 2008 Nov Exercise is now known to be beneficial for patients with inflammatory rheumatic disease. In patients with rheumatoid arthritis, exercise can improve physical performance, cardiorespiratory fitness and muscle strength, and reduce disease activity and systemic inflammation, as evidenced by reductions in erythrocyte sedimentation rate and other systemic markers of inflammation. Similar effects on physical performance and cardiorespiratory fitness have been observed in patients with polymyositis and dermatomyositis. Improved muscle performance in these patients is associated with an increased ratio of type I : type II muscle fibers and increased cross-sectional area of type II muscle fibers, suggesting that myositis-affected muscle retains the ability to respond to exercise. In addition, resistance exercise training can reduce the expression of genes involved in inflammation and fibrosis in patients with myositis, and in vitro mechanical loading of chondrocytes can suppress the expression of proinflammatory cytokines, indicating that exercise can also reduce inflammation in the local tissue environment. Further studies of the systemic and local responses underlying exercise-associated improvement in muscle performance, soft tissue integrity and health outcomes are warranted.
18076767 Apoptosis is not the major death mechanism induced by celecoxib on rheumatoid arthritis sy 2007 Synovial hyperplasia in rheumatoid arthritis (RA) has been associated with apoptosis deficiency of RA fibroblast-like synoviocytes (FLSs). Celecoxib is a non-steroidal anti-inflammatory drug that has been demonstrated to induce apoptosis in some cellular systems. We have therefore examined the dose- and time-dependent effects of celecoxib on RA FLS viability. Treatment of RA FLSs with celecoxib for 24 hours reduced their viability in a dose-dependent manner. Analysis of celecoxib-treated RA FLSs for their content of apoptotic and necrotic cells by Annexin V staining and TO-PRO-3 uptake displayed only few apoptotic cells. Caspase 3, a key mediator of apoptosis, was not activated in celecoxib-treated RA FLSs, and the presence of specific caspase 3 or pan-caspase inhibitors did not affect celecoxib-induced cell death. Moreover, we could not detect other signs of apoptosis, such as cleavage of poly(ADP-ribose) polymerase, caspase 8 or 9, or DNA fragmentation. We therefore conclude that apoptosis is not the major death pathway in celecoxib-treated RA FLSs.