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ID PMID Title PublicationDate abstract
16305761 [Generalised joint hypermobility and benign joint hypermobility syndrome. I: reproducibili 2005 Nov 21 The clinician's evaluation of the presence of joint hypermobility is most often performed through application of a joint mobility scoring system. Several systems are available, all of them based on tests of selected joints or movements. In most cases, a positive test is based on a range of motion at or above the mean range of motion +3 SD. The tests' reproducibility is good when performed by an experienced rheumatologist; however, their validity is unknown as there are no gold standards. The British Society of Rheumatology has recommended Beighton's scoring system and the level > or =4 positive tests out of 9 as the criterion for general hypermobility. The reproducibility of the criterion has been examined only once, and only with the cut level of > or =6/9 tests. At this level, the intra- and interobserver variability was 0.75 and 0.78, respectively. In another study it was demonstrated that the Beighton scoring system correlates well with a global joint mobility index and shows good agreement with two other scoring systems. The diagnostic specificity is poor with regard to the criteria for benign joint hypermobility syndrome.
15720232 Antiangiogenesis for rheumatoid arthritis. 2005 Feb Angiogenesis, i.e., the induction of new blood vessels from existing vasculature, is a crucial event in the formation and maintenance of the pannus in rheumatoid arthritis (RA). The arthritis is characterized by destruction of peripheral joints in which the cartilage and bone are destroyed by proliferative synovitis. This is characterized by infiltration of inflammatory cells and formation of new blood vessels. Angiogenesis occurs since the early stage of the disease, and supports progression of the arthritis. It has been demonstrated in animal models of arthritis that inhibition of angiogenesis reduces of the arthritis. This suggests that pharmacological inhibition of angiogenesis may play an important role in the treatment of RA. In particular, disruption of new blood vessels can not only prevent delivery of nutrients to the inflammatory site, but can also lead to vessel regression, hence reversal of disease. To sum up, since angiogenesis is central in maintaining of synovitis in RA, antiangiogenesis probably represents a therapeutic tool. This view is supported by recent studies in animal models of arthritis where antiangiogenic drugs deliver a therapeutic benefit.
16899106 Interleukin-6: discovery of a pleiotropic cytokine. 2006 In the late 1960s, the essential role played by T cells in antibody production was reported. This led to our hypothesis that certain molecules would have to be released from T cells to effect the stimulation of B cells. This hypothesis was shown to be true. There were certain factors present in the culture supernatant of T cells that induced proliferation and differentiation of B cells. The factor that induced B cells to produce immunoglobulins was initially named B cell stimulatory factor-2. The cDNA encoding the human B cell stimulatory factor-2 was cloned in 1986. At the same time, IFN-beta2 and a 26 kDa protein in the fibroblasts were independently cloned and found to be identical to B cell stimulatory factor-2. Later, a hybridoma/plasmacytoma growth factor and a hepatocyte stimulating factor were also proven to be the same molecule as B cell stimulatory factor-2. Various names were used for this single molecule because of its multiple biological activities, but these have all been unified and the molecule is now known as IL-6. Since the discovery of IL-6, rapid progress has been made in our understanding of IL-6 activities, the IL-6 receptor system and the IL-6 signal transduction mechanism. More importantly, it has been shown to be involved in a number of diseases such as rheumatoid arthritis and Castleman's disease. When taking into account all the accumulated basic research on the various aspects of this molecule, it appeared that blocking the activity of IL-6 was a feasible, new therapeutic approach for chronic inflammatory diseases.
16534537 [Dose adjustment in patients treated with infliximab in routine rheumatologic care in Germ 2006 Sep OBJECTIVE: Data from international observational studies show that a considerable proportion of patients use higher dosages of infliximab (INF) than the usual 3 mg every 8 weeks used in Germany for treatment of rheumatoid arthritis. The Data are, however, inconsistent and vary between countries. Using data from the German Biologics Register RABBIT we investigated: (1) how dosage of INF develops during the first year of treatment in routine care, and (2) how dosage translates into clinical effectiveness. PATIENTS: We analysed data from 344 patients who started a treatment with INF at their inclusion into the register and who were observed for the subsequent 12 months. Mean dosage at 3 months (after the loading dose) was 3.2 mg/kg body weight/infusion and 3.3 mg/kg after 1 year. If we also consider shortening the infusion intervals, the mean dosages at the start and after 1 year were 4.0 mg/kg body weight every 8 weeks. RESULTS: Patients who were treated with low dosages of up to 3 mg/kg/8 weeks showed significantly less improvement (EULAR response) than those who were treated with higher dosages. CONCLUSIONS: The data show that German rheumatologists are aware of the high costs of treatment and try to use the lowest possible dosage. However, for a certain proportion of the patients this might be insufficient.
16646297 [Hydrogen sulphide water balneum effect on erythrocyte catalase activity in patients with 2006 The aim of the study was to investigate, in vitro, hydrogen sulphide water (HSW) balneum effect on erythrocyte catalase activity in patients with rheumatoid arthritis. Erythrocytes from twenty nine consecutive patients with rheumatoid arthritis (11 men, 18 women) aged 54 years were obtained. The control group comprised of 30 healthy subjects with a mean age of about 40 years. Patients with rheumatoid arthritis were subdivided into two groups twice: with active disease (18 patients) and in remission (11 patients), and secondly into patients receiving (21 subjects) and not receiving (8 subjects) non-steroidal anti-inflammatory drugs. For erythrocyte catalase activity evaluation, method of Beers and Sizer was used. Catalase activity was assessed after 5, 10, 15, and 20 minutes erythrocytes incubation with HSW. The mean baseline erythrocyte catalase activity (to) was in rheumatoid arthritis patients of about 7.79 +/- 1.39 U/gHb and was significantly higher than in the control group: 6.96 +/- 2.68 U/gHb (p < 0.05). After 5 minutes incubation with HSW (t5) erythrocyte catalase activity increased, in rheumatoid arthritis patients to 8.21 +/- 1.77 U/gHb, after 10 minutes (t10) was 8.14 +/- 2.25 U/gHb, in control group: 7.58 +/- 2.50 U/gHb and 7.68 +/- 3.22 U/gHb, respectively. However the difference was not statistically significant. After 20 minutes of incubation (t20) erythrocyte catalase activity was the highest in the patients with active rheumatoid arthritis (8.33 +/- 1.96 U/gHb) and differed significantly from the patients in remission (6.69 +/- 1.27 U/gHb) and from patients not receiving non-steroidal anti-inflammatory drugs (6.04 +/- 1.08 U/gHb). In rheumatoid arthritis patients erythrocyte catalase activity was higher when compared with control group and increased during incubation with HSW. It seems HSW balneum produce an antioxidant effect on erythrocyte status in patients with rheumatoid arthritis.
15539412 Depletion of synovial macrophages in rheumatoid arthritis by an anti-FcgammaRI-calicheamic 2005 Jun BACKGROUND: Monocytes/macrophages have an important and versatile role in joint inflammation and destruction in rheumatoid arthritis (RA). OBJECTIVE: To determine the efficiency of monocyte/macrophage elimination by a new drug conjugated antibody (CD64-calicheamicin (CD64-CaMi)) directed to the high affinity receptor for IgG (FcgammaRI). METHODS: Mononuclear cells from peripheral blood and synovial fluid of patients with RA were cultured in the presence of CD64-CaMi. Cell death of monocytes/macrophages was measured by analysis of phenotypic changes (light scatter patterns, CD14 expression, and FcgammaRI expression) and nuclear DNA fragmentation. The selectivity of CD64-CaMi was checked by using FcgammaRI deficient and FcgammaRI transfected cell lines. In addition, the indirect effect of CD64-CaMi-induced macrophage cell death on arthritogenic T(h1) cell activity was determined. RESULTS: Inflammatory macrophages from RA synovial fluid, expressing increased FcgammaRI levels, were efficiently killed by CD64-CaMi through induction of DNA fragmentation. CD64-CaMi-induced cell death of monocytes/macrophages from peripheral blood of patients with RA proved less efficient. Induction of synovial macrophage death by CD64-CaMi was accompanied by efficient inhibition of proinflammatory T(h1) cytokine production. CONCLUSION: Together, the presented data suggest that elimination of macrophages through a new FcgammaRI directed CD64-CaMi is feasible. Because monocytes from peripheral blood are also eliminated by this immunoconjugate, additional experimental studies should validate its potential for local (intra-articular) application in the treatment of RA.
17544860 Exploring acupuncturists' perceptions of treating patients with rheumatoid arthritis. 2007 Jun AIMS: To outline acupuncturists' perceptions of treating patients with rheumatoid arthritis (RA), exploring the impact of practitioner affiliation to a traditional or western theoretical base. METHODS: Qualitative study utilising Grounded Theory Method. Nineteen acupuncturists were chosen via theoretical sampling. In-depth semi-structured interviews were tape-recorded and transcribed. Field notes were also taken. Emerging categories and themes were identified. RESULTS: Inter-affiliatory differences were identified in the treatments administered and the scope and emphasis of intended therapeutic effects. Limited divergence was found between acupuncturists' perceptions of treatment outcomes. Factors perceived as impacting on treatment outcomes were identified. CONCLUSIONS: Clinical trials of acupuncture in RA may have failed to administer a treatment which reflects that administered in clinical practice. Outcome measures employed in clinical trials of acupuncture in RA, as well as established outcome indices for RA, may lack the necessary breadth to accurately assess acupuncture's efficacy. Acupuncturist affiliation has demonstrable implications for the practice and research of acupuncture.
16142858 Histological patterns of synovitis and serum chemokines in patients with rheumatoid arthri 2005 Sep OBJECTIVE: Studies indicate the genetic, biological, and clinical heterogeneity of rheumatoid arthritis (RA). Recently the histological diversity of RA has been postulated. We investigated whether serum concentrations of interleukin 8 (IL-8), RANTES (regulated upon activation normal T cell expressed and secreted), and monocyte chemoattractant protein-1 (MCP-1) are correlated with histological appearance of the rheumatoid synovitis. METHODS: Using ELISA we assessed IL-8, RANTES, and MCP-1 concentrations in serum of 47 patients with RA and 30 patients with osteoarthritis (OA). RESULTS: Morphological analysis of synovial specimens distinguished 2 types of rheumatoid synovitis. Twenty-eight RA samples presented diffuse infiltrates of mononuclear cells with no specific microanatomical organization and were categorized as diffuse synovitis. In the remaining 19 specimens, classified as follicular synovitis, formation of lymphocytic follicles with germinal center-like structures was observed. Serum levels of studied chemokines were increased in patients with RA compared to the OA control group (p < 0.001 for all comparisons). Concentrations of IL-8, RANTES, and MCP-1 were highest in serum of RA patients with follicular synovitis in comparison with patients with diffuse synovitis (p < 0.01, p < 0.01, and p < 0.05, respectively) and could distinguish RA patients with these 2 histological disease patterns. Serum levels of chemokines correlated with markers of disease activity such as erythrocyte sedimentation rate, C-reactive protein concentrations, and Disease Activity Score. CONCLUSION: Distinct histological variants of rheumatoid synovitis associated with different serum levels of IL-8, RANTES, and MCP-1 reflect clinical activity of the disease and confirm the concept of RA heterogeneity.
17028793 Is three selected parameters adequate to monitor rheumatoid arthritis? 2007 Jun This pilot study was done to choose which among the five core set criteria will have more discriminating ability and which is easy to administer in a clinical setting. Forty-eight patients recently diagnosed to have rheumatoid arthritis (RA) were recruited for the study. They were assessed by a rheumatologist in each visit (initial and after 2 months of treatment), for five core measures: patient assessment, pain (measured on VAS scale), number of tender joints, health assessment questionnaire (HAQ) score, and erythrocyte sedimentation rate (ESR). All patients were treated with methotrexate 7.5 mg per week and hydroxychloroquin 400 mg per day with adequate dose of NSAIDs. Patients with associated conditions like stroke, ischemic heart disease, and other physical comorbidity were excluded. They were categorized as 20, 50, and 70% improvement, if four of the five criteria occur. The Wilcoxon signed rank test and discriminant function analysis were done to identify the order of importance of measures on influencing the outcome. The ESR followed by patient improvement scale showed the least changes, while HAQ showed the highest changes. Discriminate function analysis has been carried out to see which factors influenced in grouping them for responses with post hoc analyses of finding the order of importance of these factors in classifying the response. Pain scale, ESR, HAQ score, patient improvement scale, and tender score were in the decreasing value of importance. The pain scale, HAQ, and ESR, which are more objective and discriminate measures, are useful as measures in RA.
17165577 [Progress in research on mechanisms of anti-rheumatoid arthritis of triptolide]. 2006 Oct Extracts of Tripterygium wilfordii are effective in traditional Chinese medicine for treatment of rheumatoid arthritis (RA). Triptolide, a diterpenoid triepoxide purified from TWHF, has been identified as the major component of TWHF and might account for its therapeutic effects. To make for the clinical reasonable application and further development of triptolide, in this review was introduced the recent ten-years progress in mechanisms of anti-RA of it, including immunosuppression, anti-inflammation, inducing cell apoptosis, inhibiting vascular proliferation, protecting article cartilage and gene regulation. Triptolide is a potent immunosuppressant.
16020999 T-cell lymphopenia associated with infliximab and cyclophosphamide. 2005 Jul We report the first case of T-cell lymphopenia in a woman with rheumatoid arthritis who developed molluscum contagiosum with infliximab and cyclophosphamide. She presented in July 2000 with optic neuropathy and arthritis refractory to nonsteroidal anti-inflammatory drugs. After starting prednisone and cyclophosphamide, she became leukopenic (1.8x10 cells/microL), a condition that resolved with decreasing of the cyclophosphamide dose. In June 2002, the patient continued to have synovitis despite treatment with prednisone, cyclophosphamide, gabapentin, and celecoxib; blood counts were normal and infliximab was started. Her symptoms improved, but leukocyte counts declined (nadir of 1.5x10 cells/microL) despite discontinuing cyclophosphamide. She developed molluscum contagiosum after 8 months on infliximab (CD4 count, 492; HIV enzyme-linked immunosorbent assay and Western blot negative). Her symptoms flared after 10 months on infliximab; after the dose of infliximab was increased, her CD4 count fell to 114. Infliximab was discontinued and her leukocyte and CD4 count increased. This is the first reported case of leukopenia and T-cell suppression associated with infliximab and cyclophosphamide.
15843372 Extracellular matrix remodeling by human granzyme B via cleavage of vitronectin, fibronect 2005 Jun 24 Human granzyme B (GrB) released from cytotoxic lymphocytes plays a key role in the induction of target cell apoptosis when internalized in the presence of perforin. Here we demonstrate that GrB also possesses a potent extracellular matrix remodeling activity. Both native and recombinant GrB caused detachment of immortalized and transformed cell lines, primary endothelial cells, and chondrocytes. Cell detachment by GrB induced endothelial cell death (anoikis). GrB also inhibited tumor cell spreading, migration, and invasion in vitro. Investigation into the underlying mechanism revealed that GrB efficiently cleaves three proteins involved in extracellular matrix structure and function: vitronectin, fibronectin, and laminin. In vitronectin, GrB cleaves after an Arg-Lys-Asp (RGD) motif, which is part of the integrin-binding site found in matrix proteins. We propose that targeting of the integrin-extracellular matrix interface by GrB may allow perforin-independent killing of target cells via anoikis, restrict motility of tumor cells, facilitate lymphocyte migration, or directly reduce virus infectivity. It may also contribute to tissue destruction in diseases in which extracellular GrB is evident, such as rheumatoid arthritis and atherosclerosis.
16572283 Autoantibodies in rheumatoid arthritis: association with severity of disease in establishe 2007 Feb INTRODUCTION: Autoantibodies in rheumatoid arthritis (RA) are useful both for diagnosis and prognosis. Antibodies directed against citrullinated antigens have recently been shown to predict development of RA as well as poor outcome in early arthritis. Data on their role in established RA is limited. We studied the association of various autoantibodies in RA with its severity. MATERIALS AND METHODS: A total of one hundred and twenty nine-patients with established RA was enrolled and sera were collected and stored at -70 degrees C. Data regarding erosions, deformities, and extra-articular features were collected. IgM rheumatoid factor (RF) was measured using nephelometry and value above 20 U was considered positive. IgA RF was measured by enzyme-linked immunosorbent assay (ELISA) and value above the mean+/-2 SD of normal healthy control was taken as positive. Anti-keratin antibody (AKA) was detected by indirect immunofluorescence assay using rat esophagus as substrate. Anti-cyclic citrullinated peptide (CCP) antibodies were measured by commercial ELISA and a value above 5 U was considered as positive. RESULTS: The prevalence of various autoantibodies was: IgM RF 82.2%, anti-CCP antibodies 82.2%, AKA 51.9%, and anti IgA RF 45%. The concordance rate of anti-CCP antibodies with IgM RF was 83%, with AKA 68%, and with IgA RF 60.5%. All but one patient positive for AKA were positive for anti-CCP antibodies. The presence of IgM RF, AKA, and anti-CCP antibody was associated with joint erosions and deformities. None of the antibodies had any association with presence of extra-articular features. No association of IgA RF was seen with erosions, deformities, or extra-articular features. Among 23 seronegative RA patients, 11 were positive for anti-CCP antibodies and 6 were AKA positive. The presence of anti-CCP antibodies was associated with presence of deformities (p<0.05). CONCLUSION: Anti-CCP antibodies are present in majority of patients with established RA including seronegative patients. Both anti-CCP and AKA, in addition to conventional marker like IgM RF, are associated with severe erosive disease.
16153351 The British Rheumatoid Outcome Study Group (BROSG) randomised controlled trial to compare 2005 Sep OBJECTIVES: To examine the effectiveness and cost-effectiveness of symptomatic versus aggressive treatment in patients with established, stable rheumatoid arthritis (RA). DESIGN: A randomised observer-blinded controlled trial and economic evaluation with an initial assessment at randomisation and follow-ups at 12, 24 and 36 months. SETTING: Five rheumatology centres in England. The 'symptomatic care' patients were managed predominantly in primary care with regular visits by a rheumatology specialist nurse. The 'aggressive care' patients were managed predominantly in the hospital setting. PARTICIPANTS: Patients with RA for more than 5 years were screened in rheumatology clinics. INTERVENTIONS: The symptomatic care patients were seen at home every 4 months by a rheumatology specialist nurse and annually by the rheumatologist. The aim of treatment was symptom control. The aggressive care patients were seen at least every 4 months in hospital. Their treatment was altered (following predefined algorithms) with the aim of suppressing both clinical and laboratory evidence of joint inflammation. MAIN OUTCOME MEASURES: The main outcome measure was the Health Assessment Questionnaire (HAQ). Others included the patient and physician global assessment, pain, tender and swollen joint counts, the erythrocyte sedimentation rate and the OSRA (Overall Status in Rheumatoid Arthritis) score. X-rays of the hands and feet were performed at the beginning and end of the study. The EQ-5D was used in the health economic evaluation. Comprehensive costs were also estimated and were combined with measures of outcome to examine between-group differences. RESULTS: A total of 466 patients were recruited; 399 patients completed the 3 years of follow-up. There was a significant deterioration in physical function (HAQ) in both arms. There was no significant difference between the groups for any of the clinical outcome measures except the physician global assessment [adjusted mean difference 3.76 (95% CI 0.03 to 7.52)] and the OSRA disease activity component [adjusted mean difference 0.41 (95% CI 0.01 to 0.71)], both in favour of the aggressive arm. During the trial, second-line drug treatment was changed in 77.1% of the aggressive arm and 59.0% of the symptomatic arm. There were instances when the rheumatologist should have changed treatment but did not do so, usually because of mild disease activity. The symptomatic arm was associated with higher costs and higher quality-adjusted life-years (QALYs). There was a net cost of 1517 Pounds Sterling per QALY gained for the symptomatic arm. Overall, the primary economic analysis and sensitivity analyses of the cost and QALY data indicate that symptomatic treatment is likely to be more cost-effective than aggressive treatment in 58-90% of cases. CONCLUSIONS: This trial showed no benefit of aggressive treatment in patients with stable established RA. However, it was difficult to persuade the rheumatologist and/or the patient to change treatment if the evidence of disease activity was minimal. Patients in the symptomatic arm were able to initiate changes of therapy when their symptoms deteriorated, without frequent hospital assessment. Approximately one-third of current clinic attenders with stable RA could be managed in a shared care setting with annual review by a rheumatologist and regular contact with a rheumatologist nurse. Further research is needed into disease progression and the use of biological agents, minimum disease activity level below which disease progression does not occur, cost-effectiveness through shared care modelling, the development of a robust and fail-safe system of primary-care based disease-modifying anti-rheumatic drug (DMARD) monitoring, and predicting response to DMARDs.
16605042 Development and validation of the Emotional Intimacy Scale. 2005 Winter Although many measures have been developed to capture elements of social support, only a few include an assessment of emotional intimacy. Emotional intimacy involves a perception of closeness to another that allows sharing of personal feelings, accompanied by expectations of understanding, affirmation, and demonstrations of caring. The 5-item Emotional Intimacy Scale (EIS) was developed to assess the emotional intimacy component in one close relationship. A sample of 90 women with rheumatoid arthritis was used to assess the reliability and validity of the scale. Internal consistency and test-retest reliability for a 6-week period were .88 and .85, respectively. To assess construct validity, significant, positive correlations were obtained between the EIS and measures of social support, self-efficacy, perceived health competence, reappraisal coping behaviors, life satisfaction, and positive affect. Significant negative correlations were obtained between the EIS and perceived stress levels, helplessness, negative pain coping behaviors, pain, and fatigue. In support of criterion-related validity, the EIS predicted outcomes from an intervention program. To further assess criterion-related validity, scores on the EIS and helplessness predicted scores on two indicators of psychological well-being that measured positive affect and life satisfaction. The EIS is a brief measure of emotional intimacy with good psychometric properties.
16306476 Towards an epidemiology of rheumatoid arthritis outcome with respect to treatment: randomi 2005 Dec The results and outcomes of randomized clinical trials of leflunomide and anti-TNF therapy are much better than are seen in rheumatoid arthritis patients in the community. This appears to be an effect of the clinical trial system. The consequence of deriving effectiveness estimates from clinical trials is to overestimate the effectiveness and thereby the cost-effectiveness of rheumatoid arthritis treatments.
16956428 Homocysteine enhances cytokine production in cultured synoviocytes from rheumatoid arthrit 2006 Jul OBJECTIVE: Hyperhomocysteinemia is commonly observed in Rheumatoid Arthritis (RA) patients, thus putatively accounting in part for the high rate of cardiovascular events in these subjects. Homocysteine (Hcy) is known to exert a pro-inflammatory effect putatively contributing to the progression of atherosclerotic lesions by cytokine production from several vascular cell-types. In order to evaluate the possibility that Hcy may play a direct pro-inflammatory activity also in the joints of RA patients, we investigated: (i) the joint concentration of Hcy, and (ii) the effect of Hcy on cytokine production by unstimulated and IL-1beta-stimulated human RA cultured synoviocytes. METHODS: In 5 RA and 5 controls subjects, Hcy was measured in the blood and knee synovial fluid, and specimens of synovial tissue were taken to obtain cell cultures. Cultures were incubated with Hcy (10-100 micromol/l) +/- IL-1beta, and IL-6 and IL-8 concentrations were evaluated in the supernatants (ELISA) together with the activation of nuclear factor-kB (NF-kB) (immunocytochemistry). RESULTS: Hcy was present in synovial fluids, with a mean concentration significantly higher in RA patients than in controls (9.0 +/- 1.1 vs 5.9 +/- 1.2 micromol/l). Hcy enhanced IL-6 and IL-8 production in RA synoviocytes only (up to 35%). Moreover, Hcy produced a clear-cut activation of NF-kB in rheumatoid cells only. CONCLUSION: Hcy enhances IL-1-dependent cytokine production by rheumatoid synoviocytes at a concentration measurable in RA joints in vivo. Thus, in RA patients, Hcy may not only represent an important risk factor for the progression of cardiovascular diseases, but it may also contribute to the joint damage.
16638801 A genome-scale assessment of peripheral blood B-cell molecular homeostasis in patients wit 2006 Dec OBJECTIVE: While rheumatoid arthritis (RA) is considered a prototypical autoimmune disease, the specific roles of B-cells in RA pathogenesis is not fully delineated. METHODS: We performed microarray expression profiling of peripheral blood B-cells from RA patients and controls. Data were analysed using differential gene expression analysis and 'gene networking' analysis (characterizing clusters of functionally inter-relelated genes) to identify both regulatory genes and the pathways in which they participate. Results were confirmed by quantitative real-time polymerase chain reaction and by measuring the levels of 10 serum cytokines involved in the pathways identified. RESULTS: Genes regulating and effecting the cell-cycle, proliferation, apoptosis, autoimmunity, cytokine networks, angiogenesis and neuro-immune regulation were differentially expressed in RA B-cells. Moreover, the serum levels of several soluble factors that modulate these pathways, including IL-1beta, IL-5, IL-6, IL-10, IL-12p40, IL-17 and VEGF were significantly increased in this cohort of RA patients. CONCLUSIONS: These results outline aspects of the multifaceted role B-cells play in RA pathogenesis in which immune dysregulation in RA modulates B-cell biology and thereby contributes to the induction and perpetuation of a pathogenic humoral immune response.
15653651 Radiosynovectomy in rheumatology, orthopedics, and hemophilia. 2005 Jan Radiosynovectomy (RSV) is a local intraarticular injection of radionuclides in colloidal form for radiotherapy. First used by Fellinger et al. in 1952, the technique has now been applied for more than 50 y for treatment of resistant synovitis of individual joints after failure of long-term systemic pharmacotherapy and intraarticular steroid injections. RSV relieves pain and inflammation from rheumatoid arthritis (RA), for which it initially was used, and is accepted as an alternative to surgical synovectomy in cases of RA or other inflammatory arthropathies such as osteoarthritis and hemophiliac arthropathy. A good understanding of the clinical pathophysiology of the disease processes is mandatory, and close interdisciplinary collaboration with other clinicians who diagnose and treat patients is strongly suggested. Reported success rates range from 40% to 90% for the different joints and underlying diseases. A few well-designed prospective double-blind trials have evaluated the efficacy of RSV and justified the procedure as a viable option for treating chronic synovitis in RA or secondary to inflammatory arthropathies. In comparison with surgical synovectomy, RSV produces equivalent results, costs less, allows the patient to remain ambulatory, and is repeatable. RSV has to be considered the initial procedure of choice for the treatment of patients with hemarthrosis in hemophilia. In addition, local instillation of radiopharmaceuticals can effectively reduce effusions after implantation of a prosthesis.
15894378 The clinical potential of chemokine receptor antagonists. 2005 Jul Chemokines belong to a family of chemotactic cytokines that direct the migration of immune cells towards sites of inflammation. They mediate their biological effects by binding to cell surface receptors, which belong to the G protein-coupled receptor superfamily. Since chemokines and their receptors have been implicated in the pathophysiology of a number of autoinflammatory diseases, chemokine receptor antagonists could prove to be useful therapeutics to target these diseases. Here, we review the role of chemokines in autoimmunity, concentrating mainly on the chemokine receptors CCR1 and CCR5, and discuss the potential utility of antagonists that target these 2 receptors as they progress through the clinic.