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ID PMID Title PublicationDate abstract
17088564 Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases. 2006 Nov 14 Autoreactive memory T lymphocytes are implicated in the pathogenesis of autoimmune diseases. Here we demonstrate that disease-associated autoreactive T cells from patients with type-1 diabetes mellitus or rheumatoid arthritis (RA) are mainly CD4+ CCR7- CD45RA- effector memory T cells (T(EM) cells) with elevated Kv1.3 potassium channel expression. In contrast, T cells with other antigen specificities from these patients, or autoreactive T cells from healthy individuals and disease controls, express low levels of Kv1.3 and are predominantly naïve or central-memory (T(CM)) cells. In T(EM) cells, Kv1.3 traffics to the immunological synapse during antigen presentation where it colocalizes with Kvbeta2, SAP97, ZIP, p56(lck), and CD4. Although Kv1.3 inhibitors [ShK(L5)-amide (SL5) and PAP1] do not prevent immunological synapse formation, they suppress Ca2+-signaling, cytokine production, and proliferation of autoantigen-specific T(EM) cells at pharmacologically relevant concentrations while sparing other classes of T cells. Kv1.3 inhibitors ameliorate pristane-induced arthritis in rats and reduce the incidence of experimental autoimmune diabetes in diabetes-prone (DP-BB/W) rats. Repeated dosing with Kv1.3 inhibitors in rats has not revealed systemic toxicity. Further development of Kv1.3 blockers for autoimmune disease therapy is warranted.
16652440 Updates from B Cell Trials: Efficacy. 2006 May Recent reports of data from ongoing trials have contributed substantially to our growing understanding of the potential effectiveness and safety of B cell targeted therapy in the treatment of rheumatic diseases. In addition, the results have addressed practical questions regarding the administration of specific agents. Phase II trials of rituximab (RTX) have provided data supporting efficacy in rheumatoid arthritis (RA), including more clearly defining the role of glucocorticoids in the treatment and exploring the doses necessary to improve the signs and symptoms of RA. The Phase IIb Dose-Ranging Assessment International Clinical Evaluation of Rituximab in RA (DANCER) trial demonstrated that a significant percentage of patients achieved clinical improvement when treated with different doses of RTX as compared with those given placebo. The Phase III Randomized Evaluation of Long-Term Efficacy of Rituximab in RA (REFLEX) trial demonstrated efficacy of RTX in patients with a history of nonresponse to tumor necrosis factor inhibitors. Preliminary results of a small cohort of patients receiving RTX retreatment demonstrated efficacy with repeat administration. Phase II results of another B cell targeted therapy, anti-B lymphocyte stimulator protein, demonstrated efficacy. The efficacy of the agent, belimumab, resulted in an ACR20 response that was significantly higher in patients treated with belimumab versus placebo and in patients with RA. These findings support the hypothesis that B cells play an integral role in the pathogenesis of RA, and this report will review the efficacy results of clinical trials targeting B cells.
17049201 Cardiovascular disease in rheumatoid arthritis. 2006 Dec Epidemiological studies have disclosed an increased mortality due to cardiovascular (CV) complications in patients with rheumatoid arthritis (RA). Patients with this disease have an increased risk of left ventricular diastolic dysfunction and congestive heart failure that is unrelated to the presence of traditional atherosclerosis risk factors or ischemic heart disease. Endothelial dysfunction, an early step in the atherogenesis process, is observed in both early and long-standing actively treated patients with RA. High-resolution B-mode ultrasound studies of the common carotid artery have shown the presence of subclinical atherosclerosis, manifested by increased carotid intima-media thickness and carotid plaques, in patients with RA. Association between HLA-DRB1*04 shared epitope alleles, in particular with HLA-DRB1*0404, and endothelial dysfunction and CV mortality has also been observed in these patients. Chronic inflammation plays a pivotal role in the mechanisms associated with atherogenesis in RA. Tumor necrosis factor (TNF)-alpha is a potent proinflammatory cytokine implicated in the initiation and progression of inflammation as well as in the mechanisms associated with accelerated atherosclerosis in this disease. Anti-TNF-alpha therapy has proved to be clinically effective in patients with severe RA. Recent studies have also emphasized the positive effect of anti-TNF-alpha blockade in improving endothelial dysfunction in RA patients. However, this effect seems to be transient and in line with the persistence of chronic inflammation.
16539824 Anti-tumor necrosis factor-alpha blockade improves insulin resistance in patients with rhe 2006 Jan OBJECTIVE: Systemic inflammation, insulin resistance, and endothelial dysfunction have been implicated in the development of cardiovascular disease in rheumatoid arthritis (RA). Since insulin resistance can promote endothelial dysfunction and anti-TNF-alpha blockade yield a rapid improvement of endothelial function, we have sought to assess whether TNF-alpha blockade may also result in a reduction of insulin serum levels and improvement of insulin resistance in RA patients who require this therapy because of severe and refractory disease. METHODS: We recruited patients with RA seen over a period of 1 month at Hospital Xeral-Calde, Lugo, Spain, that were on treatment with anti-TNF-alpha monoclonal antibody-infliximab. Patients with diabetes mellitus or plasma glucose > 110 mg/dl were excluded. Fasting blood samples were taken for determination of plasma glucose and serum insulin levels immediately prior to and after infliximab infusion. RESULTS: Twenty-seven RA patients (21 women; mean age: 57.1 years; mean DAS28: 4.43) fulfilled the inclusion criteria. Dramatic reduction in the serum insulin levels and insulin/glucose index was observed following infliximab infusion. Also, a significant improvement of insulin resistance and insulin sensitivity was found. CONCLUSION: Our study confirms a rapid beneficial effect of infliximab on insulin resistance and insulin sensitivity in RA patients treated periodically with this drug. It may support the long-term use of drugs that act blocking TNF-alpha function to reduce the mechanisms implicated in the development of atherosclerosis in patients with RA.
16542359 Association of rheumatoid factor production with FcgammaRIIIa polymorphism in Taiwanese rh 2006 Apr Fcgamma receptors (FcgammaR) impact upon the development of inflammatory arthritis through immune complex stimulation and proinflammatory cytokine production. FcgammaRIIa, FcgammaRIotaIotaIotaa and FcRgammaIIIb polymorphisms were genotyped in 212 rheumatoid arthritis (RA) patients and 371 healthy control subjects using an allelic-specific polymerase chain reaction (PCR). No significant skewing in the distribution of FcgammaRIIa H/R131, FcgammaRIIIa F/V158 and FcgammaRIIIb NA1/NA2 was found between RA patients and healthy control subjects. However, a significant skewing distribution of the FcgammaRIIIa F/V158 polymorphism was observed between rheumatoid factor (RF)-positive versus RF-negative RA patients (P = 0.01). The low-affinity FcgammaRIIIa F158 allele seems to have a protective role in RF production, in comparison with the FcgammaRIIIa V158 allele (P = 0.004; OR = 0.485; 95% CI: 0.293-0.803). A high frequency of FcgammaRIIIa F/F158 was identified in RA patients with negative RF compared with RF-positive patients (for FF158 versus FV158 + VV158; P = 0.002; OR = 0.372; 95% CI: 0.194-0.713). In addition, no association was found between FcgammaRIIa H/R131, FcgammaRhoIIIa F/V158 and FcgammaRIIIb NA1/NA2 polymorphisms and other clinical parameters. The results of this study suggest that three activating FcgammaRs polymorphisms lack association with RA but FcgammaIIIa F/V158 polymorphism may influence RF production and IgG RF immune complex handling in Taiwanese RA patients.
16078317 Effect of nuclear factor-kappaB inhibition on rheumatoid fibroblast-like synoviocytes and 2005 Aug OBJECTIVE: The nuclear factor-kB (NF-kB) signaling pathway has been implicated as a molecular target for the treatment of various inflammatory diseases, such as rheumatoid arthritis (RA). In particular, IkB kinase (IKK) is considered an important molecular target because the majority of inflammatory signaling pathways mediated by NF-kB involve IKK activation. We investigated the effect of NF-kB inhibition on rheumatoid fibroblast-like synoviocytes (FLS) and collagen induced arthritis. METHODS: We evaluated the effect of IMD-0560, an inhibitor of IKK, on rheumatoid FLS in vitro and on collagen type II induced arthritis in mice. RESULTS: IMD-0560 suppressed the nuclear translocation of NF-kB and phosphorylation of IkBa induced by tumor necrosis factor-a in FLS. In addition, this compound suppressed the production of inflammatory cytokines, including interleukin 6 (IL-6), IL-8, and monocyte chemoattractant protein-1. IMD-0560 also inhibited the proliferation of FLS without showing cellular toxicity. Finally, this compound was effective against collagen induced arthritis in mice. CONCLUSION: Based on these results, IMD-0560 could be a new therapeutic agent for RA.
16855621 Microsatellite typing for DRB1 alleles: application to the analysis of HLA associations wi 2006 Oct The current methods for molecular typing of HLA-DR alleles incur a substantial financial burden when performing large population studies. In the current study, we aimed to provide much less expensive typing approach with high predictability for DRB1 genotype. We have used a panel of three microsatellite markers in the class II region (D6S2666, D6S2665 and D6S2446) for genotyping and haplotype reconstruction in a total of 1687 Caucasian (1313 RA patients and 374 controls) and 1364 Korean individuals (744 RA patients and 620 controls), all of whom were previously genotyped for DRB1. We found that a total of 88.4 and 87.4% of all observed three-marker haplotypes could determine the DR type with a positive predictive value >0.8 with high sensitivity and specificity. There was a high degree of haplotype conservation when comparing Caucasian and Asian populations. Interestingly, we found that the majority of DRB1*09 and DRB1*10 alleles share a common three-marker haplotype in both Caucasian and Asian populations. This is unexpected, since these two alleles are found on very different haplotype families. In addition, these two alleles are both associated with rheumatoid arthritis, making the elucidation of these haplotype relationships potentially important for understanding disease susceptibility.
16463431 Splitting high-dose oral methotrexate improves bioavailability: a pharmacokinetic study in 2006 Mar OBJECTIVE: To study the bioavailability of a divided higher oral dose of methotrexate (MTX), in comparison to a single dose, in adult patients with rheumatoid arthritis (RA). METHODS: A pharmacokinetic analysis was performed in 10 patients with RA taking a stable dose (25-35 mg weekly) of MTX. Separated by one week, a pharmacokinetic analysis was performed in each patient after an oral single dose, and after an equal but split dose separated by 8 hours. MTX serum concentrations were measured by a fluorescence polarization immunoassay technique. Analysis was performed by calculation of the area under the curve (AUC) by the trapezoidal rule and by means of an iterative 2-stage Bayesian population procedure, obtaining population and individual pharmacokinetic parameters. For the population analysis, data from 15 patients in our previous study comparing oral and subcutaneous administration of MTX were also used. RESULTS: The median MTX dose was 30 mg weekly (range 25-35 mg). The bioavailability of the split dose was 28% higher compared to the single dose (p = 0.007). In the population pharmacokinetic modeling, a 2-compartment model best described the serum MTX concentration versus time curves. The mean bioavailability after single-dose and split-dose MTX was 0.76 and 0.90, respectively, compared to subcutaneous administration. There was a statistically significant difference in the bioavailability of the 2 oral administration regimens (p = 0.008). CONCLUSION: The bioavailability of oral higher dose MTX in adult patients with RA can be improved by splitting the dose.
16092922 Morphological characterization of receptor activator of NFkappaB ligand (RANKL) and IL-1be 2005 Jul Bone loss represents a major unsolved problem in rheumatoid arthritis (RA). The receptor activator of nuclear factor-kappaB ligand (RANKL) is essential for the development and activation of osteoclasts, which are key mediators of bone erosions. This study was performed to determine temporal and spatial expression of RANKL compared with the potentially destructive cytokine interleukin-1beta (IL-1beta), related to progression of synovitis and joint destruction in collagen-induced arthritis (CIA), a model of RA. CIA was induced in dark agouti (DA) rats, and tissue specimens were obtained for immunohistochemical analyses at various time points before and after disease onset. Arthritis was monitored visually, and joint pathology was examined histologically. No disease-preceding expression of RANKL was detected. However, a marked increase of both RANKL- and IL-1beta-expressing cells correlated with the progression of synovial inflammation and clinical disease severity. Abundant and concomitant expression of these cytokines was detected at sites of bone erosion, where a colocalization by osteoclast-like multinuclear tartrate-resistant acid phosphatase (TRAP)+ cells was noted. In contrast to the paucity of RANKL expression in cartilage, an abundant expression of IL-1beta was demonstrated, particularly in superficial cartilage layers. These data support the hypothesis that RANKL and IL-1beta are central contributors to joint destruction in CIA.
16405258 [Autoimmune thyroid disease and associated rheumatic disorders]. 2005 Oct Musculosceletal manifestations were found in patients with hyperthyroidism as well as hypothyroidism. This article will review the available evidence that autoimmune thyroid disease is associated with: Sjögren's sydrome (SS), systemic lupus erythematosus (SLE), systemic sclerosis, rheumatoid arthritis (RA) and spondyloarthropathies. Possible pathogenesis of these manifestations has not been completely established. Sjögren's syndrome occurs in about 1/10 of patients with autoimmune thyroid disease; patients with SLE and antithyroid antibodies were significantly older than those pattiens without antibodies. Patients with systemic sclerosis and thyroid disease were significantly younger than those without antibodies. Thyroid disfunction was found three times more often in women with RA than in women with noninflammatory rheumatic diseases, and those with thyroid disease tended to have a shorter duration of arthritis.
16489254 RANTES and chemotactic activity in synovial fluids from patients with rheumatoid arthritis 2005 Dec 14 A massive accumulation of inflammatory cells in synovial tissues is a major pathological feature of rheumatoid arthritis (RA). Neutrophiles dominate synovial fluid while rheumatoid synovium is infiltrated with mononuclear cells. Mechanisms regulating influx of particular subpopulations of leukocytes into articular cavity and synovium compartment are not completely defined. An increasing amount of data supports a crucial role of a C-C chemokine RANTES in the RA pathogenesis. Our objective is to evaluate chemotactic activity for neutrophils (NCA), lymphocytes (LCA), and monocytes (MoCA) in SFs obtained from patients with RA and osteoarthritis (OA). We also aimed to characterise the relation between chemotactic activity, RANTES, and percentage distribution of leukocytes in SF. SFs from 11 patients with RA and 6 with OA were included in the study. Modified microchamber Boyden method was employed to assess chemotactic activity. Cytological and biochemical analysis of SF was performed. RANTES was measured with ELISA. Rheumatoid SFs were rich in cells with predominance of neutrophiles while osteoarthritic fluids were lymphocytic. RA SFs were also characterised by increased lactoferrin level. Both NCA and LCA were higher in SF from patients with RA (62 +/- 12 and 24 +/- 6 cells/HPF, resp) as compared to patients with OA (23 +/- 6; P < .05 and 6 +/- 2 cells/HPF; P < 0.05). The chemoattractive effect of RA SF was more pronounced on neutrophiles than on lymphocytes. RA SF expressed high RANTES levels (145+/- 36 pg/mL), while OA SF was characterised by only trace amount of this chemokine (2 +/- 1 pg/mL). We found positive correlation of RANTES with chemotactic activity for mononuclear cells (LCA + MoCA; R = 0.61; P < .05). Surprisingly, RANTES correlated also positively with neutrophiles number (R = 0.77; P < 0.001). Rheumatoid SF possesses strong chemotactic potency for leukocytes. RANTES is overexpressed in RA SF and is a potential mediator influencing intensity and composition of cellular infiltration in joints affected with inflammatory arthritis.
16627543 Pretreatment macrophage infiltration of the synovium predicts the clinical effect of both 2006 Oct OBJECTIVE: To explore whether pretreatment features of synovial tissue in patients with gonarthritis could predict the clinical effect of radiation synovectomy with yttrium-90 (90Y) and glucocorticoids or with intra-articular glucocorticoids alone. METHODS: A synovial biopsy was carried out blindly 2 weeks before treatment in 66 patients with persistent gonarthritis, who were randomised to treatment either with 90Y and triamcinolone or with placebo and triamcinolone. Immunohistochemistry was used to detect T cells, macrophages, B cells, plasma cells, fibroblast-like synoviocytes, adhesion molecules and pro-inflammatory cytokines. Stained sections were evaluated by digital image analysis. Individual patient improvement was expressed using a composite change index (CCI; range 0-12). Successful treatment was defined as CCI > or = 6 after 6 months. RESULTS: Patients with rheumatoid arthritis, psoriatic arthritis, undifferentiated arthritis and other causes of gonarthritis were included. The overall response rate was 47%. Clinical efficacy in both therapeutic groups was similar and not dependent on diagnosis. No significant differences were noted between baseline microscopic features of synovial tissue inflammation in patients with rheumatoid arthritis and in those with non-rheumatoid arthritis (ie, all diagnoses other than rheumatoid arthritis). The number of macrophages in the synovial sublining was significantly higher in responders than in non-responders (p = 0.002), independent of treatment group and diagnosis. The clinical effect was positively correlated with pretreatment total macrophage numbers (r = 0.28; p = 0.03), sublining macrophage numbers (r = 0.34; p = 0.005) and vascular cell adhesion molecule 1 expression (r = 0.25; p = 0.04). CONCLUSION: The observations support the view that intra-articular treatment either with 90Y and glucocorticoids or with glucocorticoids alone is especially successful in patients with marked synovial inflammation.
15832291 Systematic microanatomical analysis of CXCL13 and CCL21 in situ production and progressive 2005 May CXCL13 and CCL21 have been functionally implicated in lymphoid tissue organization both in the upstream phases of lymphoid tissue embryogenesis and in ectopic lymphoid neogenesis in transgenic mice. Here, we analyzed the relationship between CXCL13 and CCL21 production and lymphoid tissue organization in rheumatoid synovitis as a model of a naturally occurring ectopic lymphoneogenesis. Through systematic analysis of mRNA and protein expression, we defined the microanatomical relationship between CXCL13 and CCL21 in progressive aggregational and structural phases of synovial inflammatory infiltrate. We provide the first direct in situ evidence that production of CXCL13 and CCL21 (rather than simply protein binding) is associated with inflammatory lymphoid tissue formation and development with the demonstration, in organized aggregates, of a secondary lymphoid organ-like compartmentalization and vascular association. Notably, the presence of CXCL13 and CCL21 (protein and mRNA) was also demonstrated in non-organized clusters and minor aggregational stages, providing evidence that their induction can take place independently and possibly upstream of T-B compartmentalization, CD21(+) follicular dendritic cell network differentiation and germinal center formation. Our data support the concept that, under inflammatory conditions, CXCL13 and CCL21 participate in lymphoid tissue microanatomical organization, attempting to recapitulate, in an aberrant lymphoid neogenetic process, their homeostatic and morphogenetic physiologic functions.
17189244 Repeated B lymphocyte depletion with rituximab in rheumatoid arthritis over 7 yrs. 2007 Apr OBJECTIVE: To assess safety and efficacy of repeated B-cell depletion with rituximab in patients with rheumatoid arthritis (RA). METHODS: Thirty-seven patients with refractory RA entered into a programme of repeated B-lymphocyte depletion (up to 5 cycles, 89 cycles in total) with protocols based on the anti-CD20 monoclonal antibody, rituximab, have been observed over periods of >5 yrs (n = 22) or 3-5 yrs (n = 14). RESULTS: Twenty two subjects have been followed up for >5 yrs. Average duration of benefit per cycle was 15 months (maximum 43 months), and time to re-treatment 20 months. Nineteen patients remain on the programme. Patients were withdrawn for lack of efficacy (n = 5), hypersensitivity infusion reaction (n = 1), brevity of response (n = 8), or occurrence of adverse respiratory events (n = 1). Sixteen major lower respiratory events occurred during the 180 patient-yrs of follow-up. Of these only one had low IgG. In patients receiving rituximab +/- cyclophosphamide (cy) carcinomata have developed as follows: breast (3, +cy), ovary (1, +cy), transitional cell (1, +cy), and renal cell (1, -cy). Falls in total immunoglobulin levels to below the normal range occurred in 12 patients for IgM (undetectable levels in three after repeated cycles), seven for IgG and one for IgA, not taking into account patients who started off with low immunoglobulin levels before the first cycle. CONCLUSION: Repeated B-lymphocyte depletion over a 5-yr period appears to be an acceptable and relatively well-tolerated therapy in RA with a relatively high rate of continuation. Long-term effects on immunoglobulin levels require surveillance.
16626995 Nonpharmacological treatments in early rheumatoid arthritis: clinical practice guidelines 2006 Jul OBJECTIVE: To develop clinical practice guidelines for the use of nonpharmacological treatments in patients with early rheumatoid arthritis (RA), using the evidence-based approach and expert opinion. METHODS: A scientific committee used a Delphi prioritization procedure to select five questions. Evidence providing answers to the five questions was sought in the literature and presented to a panel of rheumatologists. The panel developed five detailed recommendations, filling gaps in evidence with their expert opinion. The strength of each recommendation was determined. RESULTS: Of the 565 publications retrieved by the literature review, 198 were included in the analysis. The five recommendations on nonpharmacological treatments for early RA were validated by a final vote among all participants. The recommendations are as follows: (1) physicians may decide to provide joint protection education to patients with potentially severe early RA, with the knowledge that structured joint protection programs have not been found effective; (2) physical exercise and sports can be recommended to patients with early RA; muscle strength exercises are advisable; (3) in patients with early RA, metatarsal pain and/or foot alignment abnormalities should be looked for regularly, and appropriate insoles should be prescribed if needed; (4) dietary measures and nutritional supplements are not indicated as part of the treatment of early RA; (5) elimination diets, particularly those with low intakes of dairy products, should be discouraged in patients with early RA. CONCLUSION: These recommendations should help to improve practice uniformity and, ultimately, to improve the management of RA.
15789642 Update in rheumatoid arthritis therapy. 2005 Feb Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by polyarticular symmetrical arthritis. Inflammatory mediators targeting joint structures produce joint inflammation with pain, functional loss, joint destruction and permanent deformity. Currently, no cure for RA exists but the increasing use of combination therapy and immunomodulatory agents has led to improved quality of life and long-term outlook for many of these patients. While traditionally employed therapies have provided limited disease suppression, advances in our understanding of the molecular pathogenesis of RA have resulted in new therapies targeting very specific components of the inflammatory process. These new treatments have shown very promising results with improved efficacy and an overall decreased toxicity profile. This review provides an overview for practicing clinicians of the current immunosuppressive therapies in RA with an emphasis on newer biological agents regarding their mechanisms of action, efficacy, side effects and monitoring recommendations. Developing therapeutics will be briefly discussed.
16141749 Access to healthcare services among persons with osteoarthritis and rheumatoid arthritis. 2005 Sep OBJECTIVE: Persons with osteoarthritis and rheumatoid arthritis frequently require access to a broad range of healthcare services. The purpose of the current study was to examine the healthcare access experiences of these two populations. DESIGN: Mail surveys were completed by 409 adults with self-reported osteoarthritis or rheumatoid arthritis who were recruited through a variety of recruitment strategies such as advertisements placed in arthritis publications, internet sources, and physician referrals. RESULTS: Participants self-reported not obtaining needed health care at high rates for several service domains, including mental health services (42%) and rehabilitation therapies (39%). The most frequent reasons for not obtaining services included lack of service coverage by the health plan and high costs. Type of arthritis was predictive of the ability to obtain primary doctor services. CONCLUSIONS: The United States healthcare system continues to focus on treating acute disorders and has yet to adapt to the growing prevalence of chronic illness and disability. Changes will be needed in both healthcare financing and delivery structures to promote access to specialized services such as mental health services and rehabilitation therapies for persons with osteoarthritis and rheumatoid arthritis.
15742458 Safety of biologic therapies--an update. 2005 Mar Tumor necrosis factor (TNF) antagonists have set a new therapeutic standard for rheumatoid arthritis (RA). Agents including infliximab, etanercept, and adalimumab have demonstrated substantial improvement in signs and symptoms, disability, and quality of life, while significantly inhibiting joint damage in early and long-standing RA. Safety issues in concert with efficacy determine risk/benefit ratio and hence a position in the therapeutic algorithm. This brief review focuses on infection, congestive heart, and malignancy.
16999205 Microvascular abnormalities in patients with rheumatoid arthritis. 2006 Sep Microvascular involvement represents one of the first apparent steps in many autoimmune diseases such as rheumatoid arthritis (RA). Early in the disease, peripheral microangiopathy may be easily recognized and studied by videocapillaroscopy. The aim of this study has been to observe the differences in labial microcirculation between healthy patients and patients suffering from RA. A total of 30 healthy patients and 30 patients suffering from RA were examined. The patients with conditions known to compromise microcirculation, such as diabetes, hypertension, or some pharmacological treatments were not included in the study. All the patients were non-smokers. Labial capillaroscopy was used to investigate the characteristics of microcirculation. Visibility, course, tortuosity, as well as the possible presence of microhemorrhages, the average caliber of the capillary loops and the number of visible capillary loops per square millimeter were evaluated for each patient. The investigation was simple, non-invasive, and repeatable for each patient. In patients suffering from RA, it was possible to observe a reduced caliber of capillaries, as well as greater elongated capillaries, in comparison to controls. This study shows that capillary alterations in patients suffering from RA occur in labial mucosa microcirculation; such evidence could be extremely important in the diagnosis of suspected RA.
15859525 Evidence of the efficacy of occupational therapy in different conditions: an overview of s 2005 May OBJECTIVE: To summarize the research evidence available from systematic reviews of the efficacy of occupational therapy (OT) for practitioners, researchers, purchasing organizations and policy-makers. DATA SOURCE: The search for systematic reviews was conducted in PubMed and the Cochrane Library (October 2004). METHODS: The reviews included were those that utilized a systematic search for evidence with regard to OT for specific patient groups. Data were summarized for patient group, interventions, outcome domains, type of study designs included, method of data synthesis and conclusions. RESULTS: Fourteen systematic reviews were included. Three reviews related to rheumatoid arthritis, four reviewed stroke and four focused on elderly people. Reviews of Parkinson's disease, multiple sclerosis, Huntington's disease, cerebral palsy and mental illnesses were also identified. The reviews of rheumatoid arthritis, stroke and elderly people showed evidence of the efficacy of OT in increasing functional abilities. Positive results were presented for quality of life and social participation in elderly people and stroke respectively. The efficacy of OT in all other patient groups is unknown due to insufficient evidence. CONCLUSION: This summary shows that elderly people and people with stroke or rheumatoid arthritis can expect to benefit from comprehensive OT. Evidence of the efficacy of specific interventions is sparse and should be addressed in future research. The evidence that does exist should be incorporated into OT practice.