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ID PMID Title PublicationDate abstract
17014003 Declining trend in the incidence of rheumatoid factor-positive rheumatoid arthritis in Fin 2006 Nov OBJECTIVE: To investigate trends in the incidence of rheumatoid arthritis (RA) in Finland. METHODS: We studied all the subjects entitled to receive drug reimbursement for chronic inflammatory joint diseases in 5/21 central hospital districts (population base about 1 million adults) in Finland during 2000. The incidence rates and the mean age at disease onset were compared with those from 1980, 1985, 1990, and 1995. RESULTS: A total of 714 subjects were entitled to drug reimbursement for chronic inflammatory joint disease that had started at the age of 16 or over. Of them, 321 satisfied the American College of Rheumatology classification criteria for RA, 198 had spondyloarthropathy, and 195 had undifferentiated oligo- or polyarthritis. The incidence of RA was 29.1/100,000 (95% CI 26.0-32.5); the figures for rheumatoid factor (RF)-positive RA and RF-negative RA were 18.2 (95% CI 15.8-21.0) and 10.8 (95% CI 9.0-12.9)/100,000, respectively. The incidence of RA was 36.9 (95% CI 32.1-42.2)/100,000 among women and 20.8 (95% CI 17.2-25.1)/100,000 among men. The age- and sex-adjusted incidence rate ratio declined from 1.00 in the referent year 1980 to 0.55 (95% CI 0.46-0.66) in 2000. A declining trend was evident for the incidence of RF-positive RA (p < or = 0.001). CONCLUSION: We verified the declining trend for the incidence of RF-positive RA in both sexes in Finland. Although the etiology of RA remains unknown, public health measures may reduce the risk of RA in the general population.
17190115 A method for pattern recognition. 2006 Winter Although pattern is a dominant concept in nursing science, only Newman's method for recognizing pattern has been fully articulated and widely used in research about the human health experience. This article proposes an alternative, less costly method to facilitate research with larger numbers of participants in clinical settings. Cluster analysis, a quasi-quantitative technique, and content analysis were combined to produce a technique for recognizing patterns of person-environment interaction. Results from two studies with persons experiencing a highly variable chronic illness, rheumatoid arthritis, indicated that this new approach identifies distinct common patterns of person-environment interaction. Sufficient detail about the nature of each pattern resulted to facilitate further knowledge development about the health experience and to provide guidance in structuring nursing care.
17153856 Early environmental exposure and the development of lupus. 2006 Systemic lupus erythematosus (SLE) is a complex trait with evidence of polygenic inheritance influenced by environmental factors. However, the precise underlying causes of SLE remain unclear. A number of environmental exposures have been associated with lupus or related autoimmune phenomena. Evidence suggests that some environmental exposures need to be present many years before the onset of SLE. Both SLE and rheumatoid arthritis (RA) can occur in very young children and this supports the possibility that important environmental factors must be present during or before this time. In addition, the immune pathology, including autoantibody production, in adult lupus may begin years before clinical disease. There is also evidence that the developing immune system demonstrates developmental plasticity and can be permanently altered or 'programmed' by the early environment. We describe how early life environmental influences including infectious exposure may lead to autoantibody production in later life thus beginning the journey that leads to autoimmune diseases such as lupus in susceptible individuals.
17083765 A proposed approach to recognise "near-remission" quantitatively without formal joint coun 2006 Nov A proposed approach is presented to recognise a status of "near-remission" in a patient with rheumatoid arthritis (RA) on the basis of patient self-report questionnaire data without formal joint counts or laboratory tests. Indices of patient-reported outcome (PRO) measures distinguish active from control treatments in RA clinical trials at levels similar to American College of Rheumatology (ACR) or disease activity score (DAS) 28 improvement levels. PRO measures on a multidimensional health assessment questionnaire (MDHAQ) can be compiled into a routine assessment of patient index data (RAPID) score. RAPID 3 includes the three PRO measures from the ACR Core Data Set - physical function, pain, and global estimate. RAPID 4 adds a self-report joint count from a rheumatoid arthritis disease activity index (RADAI). RAPID 5 adds a physician estimate of global status. RAPID cores may be classified into four preliminary proposed categories, as "near-remission" (0-1), "low severity" (1.01-2), "moderate severity" (2.01-4), and "high severity" (> 4), analogous to the four categories of the DAS28 of "remission" (< 2.6), as well as "low" (2.6-3.19), "moderate" (3.2-5.1), and "high" (> 5.1) disease activity. RAPID scores are correlated significantly with DAS28 (rho = 0.64-0.67, p < 0.001), and about 75% of patients with DAS < 2.6 have RAPID scores < 2, while about 75% of patients with DAS > 5.1 have RAPID scores > 4. RAPID data are available on one side of one page, and are feasible to collect in standard clinical care. RAPID 3 scores may be calculated in about 10 seconds, and RAPID 4 and RAPID 5 scores in 20 to 30 seconds. RAPID scores every 3 months or more on simple flowsheets can be a basis for a "continuous quality improvement" strategy in standard clinical care to recognise a need for aggressive therapy, an inadequate response to a therapy, and "near- remission" status.
17143978 The association of rheumatoid arthritis and its treatment with sinus disease. 2006 Dec OBJECTIVE: To determine if rates of sinus disease are increased in patients with rheumatoid arthritis (RA) and whether RA treatment alters the risk of sinus disease. METHODS: As part of a longitudinal study of rheumatic disease outcomes, 7,243 patients with RA, 1,667 with osteoarthritis (OA), and 447 with fibromyalgia (FM) were evaluated for important sinus problems in 2003. We defined an important sinus problem as one that required a physician visit. RESULTS: The lifetime prevalence of sinus disorders among all patients was 42.9%. During the previous 6 months 22.3% of patients with RA, 23.9% with OA, and 25.1% with FM visited a physician for a sinus problem and 22.4%, 23.9%, and 25.1% , respectively, received a prescription medication for a sinus problem. After adjustment for age and sex, the rate of physician visits for a sinus problem was significantly lower for patients with RA (22.1%) compared to patients with OA (24.8%). The strongest predictor of sinus problems among all patients was a history of allergy or asthma. Sinus problems were more common among users of etanercept: odds ratio (OR) 1.2; 95% confidence interval (CI): 1.0-1.4 univariably, and OR 1.2; 95% CI: 1.0-1.4 multivariably. Sulfasalazine (OR 0.7; 95% CI: 0.5-0.9) and leflunomide (OR 0.8; 95% CI: 0.7-1.0) had a protective effect on sinus problems. CONCLUSIONS: Sinus problems are decreased in patients with RA compared to OA and FM. Slight protective effects on sinus problems are noted with sulfasalazine and leflunomide, and a slight increase in risk of sinus problems is noted with etanercept.
16652416 Role of SLC22A4, SLC22A5, and RUNX1 genes in rheumatoid arthritis. 2006 May OBJECTIVE: Excessively suppressed expression of the SLC22A4 gene by RUNX1 is associated with the pathogenesis of rheumatoid arthritis (RA). Two etiological polymorphisms in the RUNX1 and SLC22A4 genes have been defined in a Japanese population. We studied additional polymorphisms to ascertain whether any SLC22A4/SLC22A5 haplotype is relevant for RA predisposition in a Spanish population. METHOD: We performed a case-control study comprising 416 patients with RA and 501 healthy subjects. RESULTS: The etiologic SLC22A4 mutation was rarely found in homozygosis (0.72% patients vs 0.40% controls). None of the 4 haplotypes present in the SLC22A4/SLC22A5 region in 5q31 showed significant association with RA in our Spanish cohort. The causative RUNX1 variant found in a Japanese cohort displayed the same genotype distribution in our population. However, no difference was observed when allele or genotype frequencies were compared between Spanish patients with RA and controls. CONCLUSION: The SLC22A4 and RUNX1 polymorphisms described as etiological in the Japanese study did not show a significant role in RA susceptibility in our population. The mechanism proposed by these Japanese investigators could underlie RA susceptibility irrespective of ethnicity, but the lower mutation rate present in our population hampered detection of a significant effect. Most probably the lack of mutated SLC22A4 substrate explains the absence of RUNX1 association with RA observed in our population.
15971427 RANTES promoter polymorphism as a genetic risk factor for rheumatoid arthritis in the Chin 2005 May OBJECTIVES: There is increasing evidence suggesting a role of RANTES in the pathogenesis of rheumatoid arthritis (RA) and we evaluated the possible effect of RANTES gene on the susceptibility to RA in Chinese patients. METHODS: We examined the polymorphisms at the promoter positions -28 and -403 of this gene in 151 Chinese RA patients and 149 ethnically matched healthy controls. RESULTS: The genotypic frequencies in this study were in Hardy-Weinberg equilibrium. RA patients had significantly higher frequencies of the A allele (36.1% vs. 27.5%, p = 0.024) and A/A genotype (odds ratio [OR] = 3.3, 95% confidence interval [CI] = 1.4-7.9, p = 0.005) at the promoter -403 position. Differences in allele and genotype frequencies at the promoter -28 position between patients and controls were not statistically significant (for G allele, p = 0.103 and for genotype, p = 0.106). RA patients also had a significantly higher frequency of the -28 C/G with -403 A/A compound genotype (OR = 4.6, 95% CI = 1.5-14.5, p = 0.005), and a higher frequency of the -28 G/-403 A haplotype with marginal statistical significance (OR = 1.7, 95% CI = 1.0-3.1, p = 0.059). CONCLUSION: Our results indicate that polymorphism in the promoter region of RANTES gene is associated with the susceptibility to RA in the Chinese population.
15742435 Valuing a hypothetical cure for rheumatoid arthritis using the contingent valuation method 2005 Mar OBJECTIVE: A willingness-to-pay (WTP) survey measures the value of a given intervention in money terms. We examined the WTP of Canadian patients with rheumatoid arthritis (RA) for a hypothetical cure for RA under private and public scenarios. The validity of the survey was explored by studying the association between WTP and variables thought to be associated with WTP and randomly-varied variables of the survey materials. METHODS: A telephone survey was carried out in a sample of 121 patients with RA from 5 rheumatologists affiliated with the McGill University Health Centre. In advance, patients had been sent a 4-page brochure providing a comprehensive description of the disease (including photos or no photos). The hypothetical cure for RA was presented through 2 scenarios: a private insurance implying an annual premium and a public coverage requiring additional income taxes. The survey included questions related to their WTP, socioeconomic status (ability to pay), general health, opinion about the performance of the healthcare system, and their opinion about the difficulty of the survey. For elicitation of WTP, patients were randomized to one of 3 payment cards. Mailed questionnaires concerning RA health status were also completed. A series of univariate comparisons and multivariate ordered logit regressions were carried out to examine the association of WTP and patient and study variables. RESULTS: Patients were willing to pay annually significantly more for the private program (mean 1190 Canadian dollars) than for the public program (mean 502 Canadian dollars). Annual WTP was associated with age, household income, site of care (private program), private health insurance, opinion about the performance of the public healthcare system (public program), and presence of brochure photos. The payment card did not affect WTP for either program. CONCLUSION: The WTP survey was well understood and accepted by the patients with RA. Although measures of RA-specific health status (e.g., Health Assessment Questionnaire) were not found to be associated with WTP, many variables thought to be associated with WTP were found to be related in the expected directions. Since WTP for the private program was higher than that for the public program, our study design did not fully capture altruistic valuations of RA patients. Thus, our estimates represent a lower bound on patients' WTP for an RA cure.
16583424 Effect of etanercept on fatigue in patients with recent or established rheumatoid arthriti 2006 Apr 15 OBJECTIVE: To assess the long-term impact of etanercept on fatigue in patients with recent-onset (mean duration 11 months) or established (mean duration 12 years) rheumatoid arthritis (RA). METHODS: Patients participating in either of 2 multicenter, randomized, double-blind clinical trials were included. In one trial, patients with recent-onset RA received either etanercept 25 mg twice weekly or methotrexate in a double-blind fashion for 12 months, then open label for 12 months. All patients then received open-label etanercept. In the second trial, patients with established RA received etanercept 25 mg or placebo twice weekly for 6 months in a double-blinded fashion, then open-label etanercept. Up to 46 months of followup data were included. Fatigue was measured regularly using the Health Assessment Questionnaire vitality domain. RESULTS: Patients with recent-onset RA who received etanercept had a significantly faster improvement in fatigue than those receiving methotrexate in the first 2 months. Subsequently, patients receiving etanercept and methotrexate had 23-29% and 17-24% reductions in fatigue scores, respectively. In the group with established RA, patients who received etanercept had significantly greater reductions in fatigue than those receiving placebo during the blinded period. Patients initially receiving etanercept sustained a mean fatigue reduction of 25-36% for the entire followup. Patients achieving clinically meaningful improvement in fatigue were more likely to meet the American College of Rheumatology improvement criteria. CONCLUSION: Etanercept therapy reduces fatigue in patients with recent-onset or established RA. Improvement in fatigue was sustained for up to 46 months, and correlated with other RA-relevant outcomes.
16341903 Antineutrophil cytoplasmic antibodies in Bulgarian patients with rheumatoid arthritis: cha 2005 Dec OBJECTIVE: The aim of this study was to study the prevalence, subspecificities, and immunoglobulin (Ig)G subclass distribution of antineutrophil cytoplasmic antibodies (ANCA) in 90 Bulgarian patients with rheumatoid arthritis (RA) and to investigate the clinical associations of ANCA in these patients. METHODS: The ANCA were detected by indirect immunofluorescence, while antigen specificities were determined by enzyme-linked immunosorbent assay (ELISA) directed against myeloperoxidase (MPO), proteinase 3 (PR3), bactericidal/permeability-increasing protein (BPI), lactoferrin (LF), leukocyte elastase (LE), and cathepsin G (CG). The IgG subclass reactivity of antibodies to BPI and LF was measured. RESULTS: Antineutrophil cytoplasmic antibodies were found in 18 RA patients. Only a P-ANCA fluorescence pattern was seen. Six sera reacted to BPI, five to LF, one to MPO, one to PR3, and one to CG by ELISA testing. Immunoglobulin-G1 was the predominant subclass for LF-ANCA, whereas IgG1/3 contributed mainly to BPI-ANCA. Compared to P-ANCA-negative RA patients, the P-ANCA-positive patients exhibited significantly higher inflammatory activity, as estimated by disease activity score, C-reactive protein, erythrocyte sedimentation rate, and higher levels of IgM rheumatoid factor. CONCLUSION: Twenty percent of Bulgarian patients with RA have P-ANCA in their sera. These antibodies are directed against variable antigen specificities, while ANCA positivity in RA reflects disease and inflammatory activity.
16507118 Synovial expression of IL-15 in rheumatoid arthritis is not influenced by blockade of tumo 2006 Blockade of tumour necrosis factor (TNF) is an effective treatment in rheumatoid arthritis (RA), but both non-responders and partial responders are quite frequent. This suggests that other pro-inflammatory cytokines may be of importance in the pathogenesis of RA and as possible targets for therapy. In this study we investigated the effect of TNF blockade (infliximab) on the synovial expression of IL-15 in RA in relation to different cell types and expression of other cytokines, to elucidate whether or not IL-15 is a possible target for therapy, independently of TNF blockade. Two arthroscopies with multiple biopsies were performed on nine patients with RA and knee-joint synovitis before and after three infusions of infliximab (3 mg/kg). Synovial biopsies were analysed with immunohistochemistry for expression of IL-15, TNF, IL-1alpha, IL-1ss and IFN-gamma, and for the cell surface markers CD3, CD68 and CD163. Stained synovial biopsy sections were evaluated by computerized image analysis. IL-15 expression was detected in all synovial biopsies taken at baseline. After infliximab therapy, the expression of IL-15 was increased in four patients and reduced in five. Synovial expression of IL-15 was not correlated with any CD marker or with the presence of any other cytokine. Synovial cellularity was decreased after 8 to 10 weeks of treatment with a significant reduction of the CD68-positive synovial cells, whereas no significant change was seen in the number of CD3-positive T cells and CD163-expressing macrophages. The number of TNF-producing cells in the synovial tissue at baseline was correlated with a good response to therapy. Thus, in this study the synovial expression of IL-15 in RA was not consistently influenced by TNF blockade, being apparently independent of TNF expression in the synovium. Consequently, we propose that IL-15 should remain as a therapeutic target in RA, regardless of the response to TNF blockade.
16540550 Low-cost, low-field dedicated extremity magnetic resonance imaging in early rheumatoid art 2006 Sep OBJECTIVE: To study the ability of low-cost low-field dedicated extremity magnetic resonance imaging (E-MRI) to assess and predict erosive joint damage in the wrist and metacarpophalangeal (MCP) joints of patients with early rheumatoid arthritis. METHODS: 24 previously untreated patients with rheumatoid arthritis with joint symptoms for <1 year were evaluated at the time of diagnosis and after 6 and 12 months of methotrexate treatment with conventional clinical or biochemical examinations, x rays of both hands and wrists, and E-MRI of the dominant wrist and MCP joints. RESULTS: At baseline, all patients showed magnetic resonance imaging (MRI) synovitis, and MRI erosions were detected in 21 bones (10 patients). 6 (29%) of these, distributed among two patients, were seen on x ray. One x ray erosion was not detected by MRI. At 1 year, MRI and x ray detected 15 and 8 new erosions, respectively, and 19% of MRI erosions at baseline had progressed to x ray erosions. In bones with MRI erosions at baseline, the relative risk of having x ray erosions at the 1-year follow-up was 12.1, compared with bones without baseline MRI erosions (lesion-centred analysis). If bones with baseline x ray erosions were excluded, the relative risk was 5.2. In patients with baseline MRI bone erosion or oedema, the relative risk of having x ray erosions at 1 year was 4.0, compared with patients without these signs at baseline (patient-centred analysis). CONCLUSION: In this group of patients with early rheumatoid arthritis who were treated uniformly, baseline E-MRI erosions in MCP or wrist bones markedly increased the risk of x ray erosions at the 1-year follow-up. Low-cost, low-field dedicated extremity MRI is promising for assessment and prognostication of early rheumatoid arthritis.
16565630 The indirect costs of arthritis resulting from unemployment, reduced performance, and occu 2006 Apr OBJECTIVE: The objective of this study was to assess the cost attributable to lost productivity from arthritis and the association between the degree of loss and demographic, disease-related, occupational, and psychosocial variables for people. METHODS: In a prospective study, 383 employed individuals with arthritis were recruited from southwestern Ontario, Canada. Respondents completed structured questionnaires assessing demographic, disease-related, workplace, and psychosocial variables as well as employment-related transitions at 2 time points 18 months apart. Indirect costs resulting from arthritis-related absences, reduced performance, decreased work hours, job change, and work disability were estimated. A proportional odds model was used to assess the impact of the various variables on lost productivity. RESULTS: The average cost attributable to arthritis was CAN Dollars 11,553(Dollars CAN = 0.75 Dollars US) per person per year. The largest component of the loss was the result of reduced performance at work, which accounted for 41% (Dollars 4724) of the total loss. This was followed by wage loss resulting from stopping working or changing jobs, which comprised 37% (Dollars 4309) of the total. Another 12% (Dollars 1398) and 10% (Dollars 1121) of the loss were the result of the decrease in hours of work and absenteeism, respectively. Four variables were associated with the productivity loss: greater symptom severity (odds ratio [OR] = 1.11), low or medium control over the work schedule (OR = 0.55 and 0.60, respectively), greater workspace limitation (OR = 1.10), and higher depression (OR = 1.04). CONCLUSIONS: Indirect arthritis-related costs are substantial. Our results show that not only the disease itself, but also psychosocial and work-related factors affect the magnitude of the costs.
16829990 [Antinuclear, anti-dsDNA and anti-ENA antibodies in patients affected with rheumatoid arth 2006 Apr OBJECTIVE: We evaluated the induction and clinical significance of ANA, anti-dsDNA and anti-ENA during infliximab therapy in patients with Rheumatoid Arthritis (RA) or Ankylosing Spondylitis (AS). METHODS: We tested sera from 30 RA and 30 AS patients before and during treatment with infliximab. ANA and antidsDNA were determined by indirect immunofluorescence and anti-ENA by an "in house" counterimmunoelectrophoresis. Statistical analysis was performed by X2 and McNemar's tests and U-test of Mann-Whitney. RESULTS: Eight of the 30 RA patients and 1 of the 30 AS patients were positive for ANA before treatment with infliximab. Eighteen of the 22 (81.8%) negative patients with RA and 11 of the 29 (37.9%) negative patients with AS became positive for ANA during infliximab treatment. No ANA positive patients became negative during the therapy. The difference between ANA before and after treatment resulted significant in both RA and AS patients (p=0.001). The frequency of anti-dsDNA and anti-ENA did not change significantly from baseline, in both RA and AS patients. Acquired ANA positivity was not associated with clinical signs of lupus syndrome and was not correlated with adverse events. The mean values of ESR and CRP in RA patients who became positive for ANA were significantly decreased (p=0.01 and p=0.02 respectively). CONCLUSIONS: Infliximab treatment induced a significant increase in the frequency of ANA in RA and AS patients. The significance of ANA development in these diseases is at present unknown. The significant decrease of ESR and CRP in RA patients who became positive for ANA after treatment should be investigated in a larger number of patients.
16786754 [Changes in certain biochemical markers of bone turnover in rheumatoid arthritis patients 2005 Osteoporosis associated with rheumatoid arthritis (RA) is induced by chronic inflammation. Glucocorticosteriods (GCS) applied in the treatment of RA chronically reduce production of proinflammatory cytokines (IL-1, IL-6, and TNF) which are potent stimulators of bone resorption. On the other hand they directly reduce bone mass by inhibition of osteoblast. In order to assess bone turnover the following parameters have been measured: Alkaline phosphatase (AP), alkaline phosphatase-bone formation (AP-B), deoxypirydynoline (Dpd) and carboxyterminal telopeptides of type I collagen (CTx). Based on the obtained findings we conclude that: 1. Decrease in level of AP-B and CTx may suggest reduction of bone turnover, 2. Short-term low dose GCS therapy dramatically reduce inflammation which temporarily may reduce the loss of bone mass.
15899032 Citrullinated proteins have increased immunogenicity and arthritogenicity and their presen 2005 Autoantibodies directed against citrulline-containing proteins have an impressive specificity of nearly 100% in patients with rheumatoid arthritis and have been suggested to be involved in the disease pathogenesis. The targeted epitopes are generated by a post-translational modification catalysed by the calcium-dependent enzyme peptidyl arginine deiminase (PAD), which converts positively charged arginine to polar but uncharged citrulline. The aim of this study was to explore the effects of citrullination on the immunogenicity of autoantigens as well as on potential arthritogenicity. Thus, immune responses to citrullinated rat serum albumin (Cit-RSA) and to unmodified rat serum albumin (RSA) were examined as well as arthritis development induced by immunisation with citrullinated rat collagen type II (Cit-CII) or unmodified CII. In addition, to correlate the presence of citrullinated proteins and the enzyme PAD4 with different stages of arthritis, synovial tissues obtained at different time points from rats with collagen-induced arthritis were examined immunohistochemically. Our results demonstrate that citrullination of the endogenous antigen RSA broke immunological tolerance, as was evident by the generation of antibodies directed against the modified protein and cross-reacting with the native protein. Furthermore we could demonstrate that Cit-CII induced arthritis with higher incidence and earlier onset than did the native counterpart. Finally, this study reveals that clinical signs of arthritis precede the presence of citrullinated proteins and the enzyme PAD4. As disease progressed into a more severe and chronic state, products of citrullination appeared specifically in the joints. Citrullinated proteins were detected mainly in extracellular deposits but could also be found in infiltrating cells and on the cartilage surface. PAD4 was detected in the cytoplasm of infiltrating mononuclear cells, from day 21 after immunisation and onwards. In conclusion, our data reveal the potency of citrullination to break tolerance against the self antigen RSA and to increase the arthritogenic properties of the cartilage antigen CII. We also show that citrullinated proteins and the enzyme PAD4 are not detectable in healthy joints, and that the appearance and amounts in arthritic joints of experimental animals are correlated with the severity of inflammation.
16402200 The occurrence of a geode in the olecranon of a patient with rheumatoid arthritis. 2006 Mar Geode, a subchondral cyst, is sometimes seen in the femur, knee, or wrist in a patient with rheumatoid arthritis (RA). But the onset of a giant geode at the olecranon is extremely rare in a patient with RA. We describe herein a rare case of a giant geode at the olecranon in a patient with RA.
16713715 Spontaneous development of autoimmune arthritis due to genetic anomaly of T cell signal tr 2006 Aug A point mutation of the gene encoding ZAP-70, a key signal transduction molecule in T cells, results in spontaneous development of T cell-mediated autoimmune arthritis in mice homozygous for the mutation. The genetic anomaly alters differentiation and selection of T cells in the thymus, leading to thymic production of arthritogenic autoimmune T cells. The arthritogenic T cells persist in the periphery and elicit arthritis when activated by microbial agents that stimulate innate immunity. This model is instrumental in understanding how genetic variations in T cell signal transduction, together with environmental influences, contribute to the development of autoimmune disease.
16980216 Inhibition of angiogenic pathways in rheumatoid arthritis: potential for therapeutic targe 2006 Oct Angiogenesis is a significant and possibly primary event in the pathogenesis of inflammatory diseases including arthritis. Abnormalities of vascular morphology and angiogenesis have been described at the macroscopic, histological and molecular levels in the synovial membrane in rheumatoid, seronegative and degenerative arthritis. The vascular endothelium is an active organ that participates in the initiation and maintenance of the inflammatory response. Endothelial cells (EC) are activated by a variety of stimuli to express surface adhesion molecules to bind and facilitate, via an active process, the movement of white blood cells such as neutrophils, macrophages and lymphocytes into the target tissue. The main stimuli known to activate EC and initiate angiogenesis include hypoxia, inflammatory mediators and mechanical stress. Irrespective of the trigger a series of messages, such as cytokine release, production of growth factors and subsequent downstream molecular messages, result in changes to vessel permeability, EC proliferation and migration, disruption of the basement membrane and formation of new vascular tubes. Several key growth factors are known to upregulate EC activation and proliferation leading to the sprouting of new vessels that then stabilise and mature, recruiting smooth muscle pericytes to consolidate vessel wall structure. In this review the process of angiogenesis in the arthritic joint, including the stimuli and molecular pathways will be discussed and potential therapeutic targeting of critical steps will be highlighted.
16205141 Outcomes are poor after treatment of sepsis in the rheumatoid shoulder. 2005 Oct Currently, there is little information regarding treatment of shoulder sepsis in patients with rheumatoid arthritis. This study examines the prognosis and outcome after operative treatment of native shoulder infection in patients with rheumatoid arthritis. Seventeen patients were retrospectively reviewed (20 shoulders) after surgical intervention for shoulder sepsis between 1982 and 2002. Nine patients (12 shoulders) were associated with multiple joint infections. The most common isolated organism from cultures was Staphylococcus aureus in 15 shoulders. Three patients died during initial admission to the hospital (at 7 days, 5 months, and 6 months) because of multisystem organ failure and multiple joint infections. Fourteen patients (15 shoulders) survived for followup, with two excellent, six satisfactory, and seven unsatisfactory results. Mean active elevation was 100 degrees. Further surgery was required in three patients: one synovectomy and two shoulder arthrodeses. In this study, patients with shoulder sepsis with rheumatoid arthritis were found to have a high rate of multiple joint sepsis and unsatisfactory shoulder function.