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ID PMID Title PublicationDate abstract
10759783 Increased synovial fluid levels of soluble CD23 are associated with an erosive status in r 2000 Apr Synovial fluid (SF) levels of soluble CD23 (sCD23) were determined in 96 patients presenting with an inflammatory knee effusion (73 with RA and 23 with reactive arthritis (ReA) serving as a control inflammatory non-erosive group) and were correlated with the degree of joint destruction, with local immune parameters (IL-1beta, IL-3, IL-4, IL-6, IL-8, IL-10, IL-12 and sCD25) and with serum markers of inflammation, C-reactive protein and erythrocyte sedimentation rate. RA patients, classified as erosive or not according to Larsen's grade, were separated as follows: (i) 13 patients with non-erosive RA; (ii) 16 RA patients with erosions in hands but not in knees, matched for disease duration with the first group; (iii) 44 RA patients with hand and knee erosions, matched with the second group for rheumatoid factor positivity but of longer disease duration. SF sCD23 levels were significantly increased in both erosive RA groups compared with non-erosive diseases, whether RA or ReA (P < 0.05), whose SF levels were not different. SF IL-10 showed a similar profile to that of SF sCD23 and was the only other parameter characteristic of erosive RA, but no direct correlation was found between the two. SF sCD23 was significantly correlated with IL-12 (r = 0.65, P = 0.0001) and sCD25 (r = 0.39, P = 0.0019) exclusively in the two erosive RA populations. In conclusion, these data showing that increased levels of sCD23 are not only found in the SF of erosive joints but also in knee SF of patients with erosive RA but without knee x-ray-diagnosed erosions suggest that this parameter might be of predictive value for joint destruction. Longitudinal studies are however needed to confirm its potential clinical interest.
9013133 A modified form of low-density lipoprotein with increased electronegative charge is presen 1997 Reactive oxygen species (ROS) are pro-inflammatory factors in the pathogenesis of rheumatoid arthritis. During inflammation, the amount of low-density lipoprotein (LDL) in the inflamed joint is increased. LDL is known to be susceptible to oxidation by ROS. Oxidized LDL may serve as a mediator for joint damage, further exacerbating the inflammatory process. LDL isolated from synovial fluid and plasma from individual patients (paired samples) with rheumatoid arthritis or osteoarthritis was characterized by crossed immunoelectrophoresis. On analysis by this technique, synovial fluid LDL from most patients with rheumatoid arthritis contained two peaks: one corresponding to normal plasma native LDL, and the other having an increased electrophoretic mobility associated with oxidized LDL. Paired plasma LDL samples contained native LDL alone, as did paired synovial fluid and plasma LDL from patients with osteoarthritis. Thus, in addition to native LDL, a second form of LDL was shown to be present in rheumatoid synovial fluid, which had properties consistent with those of oxidized LDL.
12086311 Genetic analysis of collagen-induced arthritis in rats: a polygenic model for rheumatoid a 2001 Dec Collagen-induced arthritis (CIA) is a useful model for dissecting the genetic patterns underlying susceptibility to rheumatoid arthritis (RA) and related chronic/inflammatory autoimmune diseases. CIA exhibits three phenotypes characteristic of autoimmune disease pathogenesis: abnormal levels of immune reactivity to self antigens; chronic inflammation of target organs expressing that specific autoantigen; activation and direct participation of invading mononuclear cells and resident tissue fibroblasts in organ damage. Over 25 different quantitative trait loci (QTL) regulating arthritis severity and autoantibody in rats with CIA are mapped. QTL-congenic strains show that certain CIA-QTLs can modulate arthritis independently These monogenic models are proving to be highly informative for fine mapping and function studies, revealing gender effects and evidence of gene clusters. Recent genome scans of RA populations identified RA-susceptibility loci in chromosome regions homologous to rat chromosomal segments housing CIA-QTLs. Also, CIA-QTLs frequently co-localize with susceptibility QTLs mapped in other rat arthritis models induced with non-immunogenic adjuvant oils and/or in rat autoimmune models of multiple sclerosis and diabetes. Common autoimmunity genes and inflammation genes important to several human diseases are likely being detected in the various rat disease models. Continued dissection of the genetic underpinnings of rat arthritis models should provide candidate genes for investigation in human patients and lead to a clearer understanding of the complex genetics of RA.
11510144 [Active forms of oxygen and nitrogen in blood cells of patients with rheumatoid arthritis: 2001 Infrared pulse laser therapy was studied for its impact on the production of active forms of oxygen and nitrogen by neutrophils from patients with rheumatoid arthritis (RA). The authors determined the non-activated and PMA-activated production of superoxide anion-radical, peroxynitrite, peripheral neurophilic NAD.PH-oxidase and superoxide dismutase activities, and the red blood cell concentrations of reduced glutathione. Before therapy, non-activation RA neurophilic production of superoxide was much higher than in donors. Laser therapy made this parameter normal. Similarly, neutrophilic peroxynitrite production (defined by dihydrorhodamine oxidation) in RA patients was 1.7 times higher than the normal values. IF-laser therapy decreased peroxynitrite production to the values observed in donors. It is important that the therapy caused increased SOD activity (that was lower in RA patients prior to therapy) up to apparently control values. Thus, IF-laser therapy has a certain antioxidative effect by increasing SOD activity in RA patients' blood cells and reducing the production of highly reactive oxygen and nitrogen forms.
11094432 Association of MHC and rheumatoid arthritis. HLA polymorphisms in phenotypic variants of r 2000 Genes in the human leukocyte antigen (HLA) region remain the most powerful disease risk genes in rheumatoid arthritis (RA). Several allelic variants of HLA-DRB1 genes have been associated with RA, supporting a role for T-cell receptor-HLA-antigen interactions in the pathologic process. Disease-associated HLA-DRB1 alleles are similar but not identical and certain allelic variants are preferentially enriched in patient populations with defined clinical characteristics. Also, a gene dosing effect of HLA-DRB1 alleles has been suggested by the accumulation of patients with two RA-associated alleles, especially in patient subsets with a severe disease course. Therefore, polymorphisms in HLA genes are being explored as tools to dissect the clinical heterogeneity of the rheumatoid syndrome. Besides HLA polymorphisms, other risk genes will be helpful in defining genotypic profiles correlating with disease phenotypes. One such phenotype is the type of synovial lesion generated by the patient. HLA genes in conjunction with other genetic determinants may predispose patients to a certain pathway of synovial inflammation. Also, patients may or may not develop extraarticular manifestations, which are critical in determining morbidity and mortality. HLA genes, complemented by other RA risk genes, are likely involved in shaping the T-cell repertoire, including the emergence of an unusual T-cell population characterized by the potential of vascular injury, such as seen in extraarticular RA.
10791615 The outcome of knee synovitis in early arthritis provides guidelines for management. 2000 The aim of the study was to examine the clinical outcome of patients presenting to an early arthritis clinic with synovitis of the knee. The patients were assessed at presentation for evidence and pattern of joint inflammation. These patients were then reassessed at 3, 6 and 12 months and thereafter annually to determine clinical outcome. One thousand six hundred and thirty-three consecutive referrals were examined, 903 of whom had early synovitis. One hundred and thirty had knee synovitis at presentation, of whom 73 fulfilled ACR criteria for rheumatoid arthritis (RA) during the study. All 73 presented with a symmetrical polyarthritis that included the small joints and had persistent disease at 1 year. Of the remaining 57 patients, 61% of those presenting with an oligoarthritis and 33% with a polyarthritis (including knee synovitis) were in remission at 1 year. None of those presenting as a monoarthritis of the knee had inflammation at 1 year or fulfilled ACR criteria for RA at any time. It was concluded that patients presenting with knee synovitis in the absence of a small joint polyarthritis usually have a benign course following standard therapy. No patient who presented with monoarthritis developed RA. Knee synovitis as part of a polyarthritis (even when not fulfilling ACR criteria) probably justifies disease-modifying antirheumatic drug at presentation.
11328533 Glomerular crescents in renal amyloidosis: an epiphenomenon or distinct pathology? 2001 Mar There have been several reports of cases of renal amyloidosis with glomerular crescents. However, it is not clear whether the association is fortuitous or pathogenic related. The present study analyzed 105 cases of renal amyloidosis (61 autopsy cases and 44 biopsy cases) and found glomerular crescents in 14 (13.3%) cases. Among the 14 cases with crescents, a female predominance was noted (male: female, 3: 11) and rheumatoid arthritis was the most common primary disease of amyloidosis. Immunohistochemical analysis demonstrated amyloid protein of AA type in 12 cases. According to the histologic classification, there were 11 cases of mesangial nodular type, which was almost exclusively accompanied by AA amyloid deposition. Of note, the incidence of crescents neither correlated with the extent of amyloid deposition nor the presence of nephrotic syndrome. By contrast, localization of amyloid deposition was closely related to crescent formation. Moreover, electron microscopic observation displayed rupture of the glomerular basement membrane at the site of amyloid deposition. Our results indicated that glomerular crescents were more frequently associated with renal amyloidosis than previously appreciated. Rupture of the fragile glomerular basement membrane by amyloid deposition, as revealed by immunostaining and electron microscopy, may be the mechanism of crescent formation. We suggest that glomerular crescents are a distinct pathology associated with renal amyloidosis, not fortuitous conditions.
10415720 Design and synthetic considerations of matrix metalloproteinase inhibitors. 1999 Jun 30 Experimental evidence confirms that the matrix metalloproteinases (MMPs) play a fundamental role in a wide variety of pathologic conditions that involve connective tissue destruction including osteoarthritis and rheumatoid arthritis, tumor metastasis and angiogenesis, corneal ulceration, multiple sclerosis, periodontal disease, and atherosclerosis. Modulation of MMP regulation is possible at several biochemical sites, but direct inhibition of enzyme action provides a particularly attractive target for therapeutic intervention. Hypotheses concerning inhibition of specific MMP(s) with respect to disease target and/or side-effect profile have emerged. Examples are presented of recent advances in medicinal chemistry approaches to the design of matrix metalloproteinase inhibitors (MMPIs), approaches that address structural requirements and that influence potency, selectivity, and bioavailability. Two important approaches to the design, synthesis, and biological evaluation of MMPIs are highlighted: (1) the invention of alternatives to hydroxamic acid zinc chelators and (2) the construction of nonpeptide scaffolds. One current example in each of these two approaches from our own work is described.
10685570 Rheumatoid arthritis of the temporomandibular joint with herniation into the external audi 2000 Feb Previous authors have shown that soft tissue can present in the external auditory canal via a patent foramen of Huschke. One case represented a patient with psoriatic arthritis and a polyp in the external auditory canal. Typically, neoplastic, inflammatory, or degenerative lesions of the temporomandibular joint do not present in the external auditory canal. We present a patient with rheumatoid arthritis of the temporomandibular joint and soft tissue herniation into the external auditory canal. The case, and a discussion of possible causes, are presented.
11852819 [The role of cyclooxygenase and prostaglandins in the pathogenesis of rheumatoid arthritis 2001 Nov Rheumatoid arthritis (RA) is a systemic inflammatory disease with polyarticular synovitis leading to formation of rheumatoid pannus and subsequent erosion of articular cartilage and bone. Prostaglandins (PGs)--a group of arachidonic acid metabolites found at elevated levels in synovial fluid and synovial membrane are considered to play a pivotal role in development of vasodilatation, fluid extravasation and pain in synovial tissues. Moreover, there is increasing evidence that PGs (especially prostaglandin E2) are mediators involved in complex interactions leading to development of erosions of articular cartilage and juxta-articular bone. Cyclooxygenase is an enzyme playing crucial role in PGs production. It is known that two forms of cyclooxygenase exist: cyclooxygenase-1 (COX-1) playing house-keeping functions and cyclooxygenase-2 (COX-2) involved in inflammatory responses. Synovial tissues from patients with RA are shown to contain COX-2 and to a less extent COX-1. COX-2 expression in rheumatoid synovium is induced by proinflammatory cytokines, mainly IL-1, while corticosteroids are capable of inhibiting COX-2 expression. The understanding of crucial role of COX-2 in synovial inflammation led to development of new group of anti-inflammatory agents--selective COX-2 inhibitors, that inhibit specifically COX-2, providing effective anti-inflammatory action without the side effects associated with inhibition of COX-1. In the context of widespread use of selective COX-2 inhibitors hypothetical role of COX-1 in RA pathology should be elucidated.
10894375 Results of a single total knee prosthesis compared with multiple joint replacement in the 2000 We present the clinical results of total knee replacement (TKR) in 133 patients who had two or more major joints of the lower limbs replaced, and compare them to the outcome in 406 patients with an isolated TKR. 383 patients had osteoarthritis (OA) and 136 had rheumatoid arthritis (RA) and these were assessed separately. A meniscal bearing prosthesis was used. The functional score was high and there was no statistically significant difference in the incidence of complications between the two groups.
9588271 Education in rheumatology. 1998 Jan The increasing burden of arthritis and musculoskeletal conditions in both developed and developing societies is shown by national and community-based surveys. Many complaints are sufficiently severe to cause disability and loss of time from work. Medical care is provided most often by primary health care physicians who are often inadequately trained to handle these conditions. Better medical student education that focuses on common community problems remains crucial. Strong rheumatology units with a commitment to teaching and research are necessary to redress any imbalance as new curricula are developed. Such units also have to take responsibility for primary health care physician and nurse education in how to manage common musculoskeletal problems. Arthritis Foundations and patient support groups have a role in public education and in increasing community knowledge on the causes and prevention of some common conditions so as to assist in improving overall care. New initiatives in professional and public education have given encouraging results, but further changes in community attitudes and perceptions of chronic conditions are necessary and are within the scope of most Arthritis Foundations' key objectives.
10458086 Erythema elevatum diutinum complicated by rheumatoid arthritis. 1999 Jul A 53-year-old female developed erythema elevatum diutinum (EED) twelve years after the onset of rheumatoid arthritis. The arthritis had been well controlled for the last several years. Annular purpuric macules were characteristically complicated by common nodular and plaque lesions. Both leukocytoclastic vasculitis and fibrosis were observed in the macular lesions, indicating that the lesions were a manifestation of an early phase of EED. Both types of skin lesions disappeared with treatment with dapsone. They have not relapsed for two years after stopping the dapsone. The leukocytoclastic vasculitis was thought to have developed independently of the rheumatoid arthritis. She had noticed sicca symptoms two years before the appearance of EED, but she did not satisfy the diagnostic criteria for Sjögren's syndrome.
10743797 Use of antikeratin antibodies to distinguish between rheumatoid arthritis and polyarthriti 2000 Mar OBJECTIVE: To investigate whether antikeratin antibodies (AKA) could be useful in the differential diagnosis of patients with rheumatoid arthritis (RA) compared to patients with hepatitis C virus (HCV) associated polyarthritis, who are seropositive for rheumatoid factor (RF). METHODS: AKA were assayed in 3 different groups of patients; all were RF seropositive: Group 1: 25 patients with HCV associated polyarthralgia or arthritis. Group 2: 33 patients with RA. Group 3: 13 patients with autoimmune disorders other than RA. Fifteen healthy individuals served as controls. RESULTS: AKA were detected in 20/33 patients with RA (60.6%) compared to only 2/25 patients (8%) with HCV associated arthritis (p < 0.0001). AKA were observed in 2/13 patients of Group 3 (15.3%). These results were also statistically different from those of patients with RA (p = 0.008). AKA were not found in the sera of the healthy controls. CONCLUSION: AKA is a useful marker to differentiate patients with RA from those with hepatitis C arthritis.
9002008 Rheumatology visit frequency and changes in functional disability and pain in patients wit 1997 Jan OBJECTIVE: To determine if the frequency of visits to rheumatologists by patients with rheumatoid arthritis (RA) is associated with either short term (6 month) or longterm (10 year) changes in functional disability or pain. METHODS: Information on health care utilization and health status was obtained for up to 10 years by biannual mailed Health Assessment Questionnaires (HAQ) in a community based cohort of patients with RA. We studied the relationship between the frequency of visits to rheumatologists and changes in functional disability and pain among 127 patients who were treated by a rheumatologist at least once each year. RESULTS: The median visit frequency was 7.2 visits/year (range 2-17.5 visits/year). The number of rheumatology visits was significantly associated with short term changes in both functional disability and pain: each additional visit in a 6 month study interval was associated with a decrease in the pain score in the current interval by an average of 0.02 points (on a 3 point scale), and each additional visit was associated with a decrease in the HAQ Disability Index in the subsequent 6 month interval by an average of 0.007 points (on a 3 point scale). In analyses of longterm changes in health status, there was a U-shaped relationship between the frequency of rheumatology visits and the rate of progression of functional disability over time, with the lowest rates associated with average visit frequencies of between 7 and 11 visits/year. Average pain scores over time were positively correlated with the average annual frequency of rheumatology visits (r = 0.25). CONCLUSION: More frequent visits to rheumatologists were associated with greater improvements in pain and functional disability over periods of 6 and 12 months, respectively. Rates of progression of functional disability over time were also higher among patients with less than 7 visits/year than among those with 7-11 visits/year, suggesting that the outcomes of these patients might have been improved with more frequent visits.
11279784 Herbal therapy for treating rheumatoid arthritis. 2001 BACKGROUND: The increasing popularity of the use of complementary and alternative interventions or treatments appears to be particularly evident amongst people with chronic disease. In the treatment of rheumatoid arthritis, one therapy that has been identified as having potential benefit, is herbal medicine (phytotherapy). OBJECTIVES: To assess the effectiveness of herbal therapies in the treatment of rheumatoid arthritis. SEARCH STRATEGY: We developed a search strategy using terms to include all forms of arthritis combined with herbal medicine. We searched the following electronic databases from 1966 to 2000: MEDLINE, EMBASE, CISCOM, AMED, CINAHL, Cochrane Controlled Trials Register (CCTR), Cochrane Musculoskeletal specialized register, Dissertation Abstracts, BIDS ISI and the Cochrane Complementary Medicine Fields Specialized Register. This was supplemented by searching the reference lists from retrieved trials. SELECTION CRITERIA: All randomized trials of herbal interventions in rheumatoid arthritis, compared to placebo. Two reviewers independently read and selected each potential study according to the criteria published in an a priori protocol. Papers of any language were included. DATA COLLECTION AND ANALYSIS: Data were extracted independently by the same two reviewers and an assessment of methodological quality was conducted. MAIN RESULTS: Eleven studies met the inclusion criteria. Seven of the studies compared gamma-linolenic acid (GLA) to placebo although three of these were not suitable for data pooling. The remaining studies considered four different herbal interventions and were assessed individually. All of the GLA studies found some improvement in clinical outcomes but methodology and study quality was variable, making it difficult to draw conclusive results. However, the better quality studies suggest potential relief of pain, morning stiffness and joint tenderness. With the exception of one intervention (Tripterygium wilfordii hook F), no serious side effects were reported. REVIEWER'S CONCLUSIONS: There appears to be some potential benefit for the use of GLA in rheumatoid arthritis although further studies are required to establish optimum dosage and duration of treatment. The single studies are inconclusive.
10074195 Disease-inducible transgene expression from a recombinant adeno-associated virus vector in 1999 Apr Rheumatoid arthritis (RA) is a systemic autoimmune disease affecting 1% of the world's population, with significant morbidity and mortality. In this study, we investigated a recombinant adeno-associated virus (rAAV) vector for its potential application in RA gene therapy. rAAV encoding Escherichia coli beta-galactosidase was injected into rat joints which had already been induced into acute arthritis after local lipopolysaccharide (LPS) administration, and the efficiency of in vivo transduction was evaluated. We observed a striking correlation between vector transgene expression and disease severity in arthritic joints. The inflammatory reaction peaked at 3 to 7 days after LPS treatment, and, at the same time, 95% of the synoviocytes had high-level transgene expression. Gene expression diminished to the basal level (5%) when the inflammation subsided at 30 days after LPS treatment. More importantly, the diminished transgene expression could be efficiently reactivated by a repeated insult. The transgene expression in normal joints transduced with rAAV remained low for a long period of time (30 days) but could still be induced to high levels (95%) at 3 to 7 days after LPS treatment. This is the first demonstration of disease state-regulated transgene expression. These findings strongly support the feasibility of therapeutic as well as preventative gene transfer approaches for RA with rAAV vectors containing therapeutic genes, which are expected to respond primarily to the disease state of the target tissue.
9028833 Characterization of a SV40-transformed rheumatoid synovial fibroblast cell line which reta 1997 Jan A chimeric Adenovirus-Simian Virus 40 (AdSV40) containing the large T antigen was used to transform rheumatoid synovial fibroblasts. A rheumatoid synovial fibroblast cell line was established by infection of primary rheumatoid arthritis (RA) synovial fibroblasts at Passage 10 with AdSV40 recombinants followed by selection in semisoft agarose cultures. The transformed cells grew anchor independent, exhibited continuous proliferation (> 65 passages) in monolayer culture, and formed multiple visible foci. The transformed synovial fibroblasts showed expression of the simian virus 40 large T antigen in the nucleus as determined by immunofluorescence staining. In addition, indirect immunofluorescence staining demonstrated that the transformed cells stained specifically with a fibroblast-specific antibody 1B10. Studies involving expression of metalloproteinases showed that collagenase and stromelysin were induced by phorbal 12-myristate 13-acetate (PMA), and such an induction was repressed by dexamethasone typical of primary RA fibroblasts. Levels of mRNAs for IL-1 beta, TNF-alpha, and c-jun were increased by PMA, and the mRNA transcripts of these genes were also repressed by addition of dexamethasone to the culture media. Our results indicate that transformed RA synovial fibroblasts display a similar gene expression pattern in response to PMA and dexamethasone as observed for untransformed primary RA synovial fibroblasts. These transformed rheumatoid arthritis synovial fibroblast cells provide an ideal cell culture model in which to test the efficacy of novel arthritis gene therapy reagents.
9479310 Rheumatoid arthritis. Designing and implementing a treatment plan. 1998 Feb Treating rheumatoid arthritis can be very satisfying when patients participate fully in designing and implementing their therapeutic strategy. However, the strategy's success depends on early intervention and disease modification. Many patients do well when education, rest, diet, exercise, and drug therapy are incorporated into an individualized regimen.
11375296 Diagnostic accuracy of the anti-citrulline antibody assay for rheumatoid arthritis. 2001 Jun BACKGROUND: Rheumatoid arthritis (RA) is the most common autoimmune rheumatic disease, but specific and practicable tests for its diagnosis are lacking. We evaluated the diagnostic accuracy of a new commercial ELISA in detecting anti-cyclic citrullinated peptide (CCP) antibodies for the diagnosis of RA. METHODS: Anti-CCP antibodies were determined in 330 serum samples: 98 from RA patients and 232 from controls, including patients with connective tissue diseases, other rheumatic diseases, viral infections, Lyme disease, autoimmune thyroiditis, cancer, and monoclonal gammopathy, and sex- and age-matched healthy subjects. Intra- and interassay CVs were 5-13% and 9-17%, respectively. Rheumatoid factor (RF) was also assayed in every sample, and results were compared to anti-CCP for sensitivity and specificity. RESULTS: At a cutoff value of 50 units, sensitivity was 41% (confidence interval, 31-50%) and specificity was 97.8% (95-100%). Anti-CCP-positive RA patients had a mean antibody concentration of 1100 units (range, 57-3419 units), and anti-CCP-negative RA patients and controls had mean values of 7.6 and 6.8 units, respectively (range, 1-39 units). The area under the ROC curve was 0.71 (95% confidence interval, 0.63-0.78). RF had a higher sensitivity (62%) and a lower specificity (84%) than anti-CCP. When the two antibodies were used together, specificity was 99.6%. CONCLUSION: Anti-CCP antibody testing may be useful if performed concomitantly with RF assay to diagnose patients with suspected early RA.