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ID PMID Title PublicationDate abstract
12111074 MR imaging assessment of clinical problems in rheumatoid arthritis. 2002 Jul Although MR imaging has been increasingly recognized as a useful tool in the diagnosis of early rheumatoid arthritis (RA) and in the assessment of disease activity, these applications have not yet been usually included in the routine management of this condition. Our goal is to review the current role of MRI in the everyday clinical management of patients with RA. The usefulness of MRI in the evaluation of articular and para-articular changes in specific locations, mainly the craniocervical region and the temporomandibular joint, are reviewed. Clinical problems derived from local extra-articular involvement, such as tenosynovitis, "rice-bodies" bursitis, and Baker's cyst rupture, are also described. Finally, we also review the value of MRI in evaluation of some complications of RA such as tendinous rupture, osteonecrosis, stress fracture, and septic arthritis/osteomyelitis.
12223110 Anti-TNF-alpha antibody allows healing of joint damage in polyarthritic transgenic mice. 2002 Anti-tumor-necrosis-factor-alpha (TNF-alpha) monoclonal antibody was used to treat Tg197 transgenic mice, which constitutively produce human TNF-alpha (hTNF-alpha) and develop a progressive polyarthritic disease. Treatment of both young (7- or 8-week-old) and aged (27- or 28-week-old) mice commenced when at least two limbs showed signs of moderate to severe arthritis. The therapeutic efficacy of anti-TNF-alpha antibody was assessed using various pathological indicators of disease progression. The clinical severity of arthritis in Tg197 mice was significantly reduced after anti-TNF-alpha treatment in comparison with saline-treated mice and in comparison with baseline assessments in both young and aged mice. The treatment with anti-TNF-alpha prevented loss of body weight. Inflammatory pathways as reflected by elevated circulating hTNF-alpha and local expression of various proinflammatory mediators were all diminished by anti-TNF-alpha treatment, confirming a critical role of hTNF-alpha in this model of progressive polyarthritis. More importantly, the amelioration of the disease was associated with reversal of existing structural damage, including synovitis and periosteal bone erosions evident on histology. Repair of cartilage was age dependent: reversal of cartilage degradation after anti-TNF-alpha treatment was observed in young mice but not in aged mice.
12477226 Diagnostic value of radiographs of the hands and feet in early rheumatoid arthritis. 2002 Oct The extent to which radiographs of the hands and feet can contribute to the diagnosis of early rheumatoid arthritis (RA) has received little research attention. Yet, the workup for recent-onset inflammatory joint disease usually includes radiographs of the hands and feet. We reviewed the literature for data on the value of these radiographs for diagnosing early RA. We sought to determine whether radiographic changes in the hands and feet constitute a valid diagnostic criterion, i.e., show good discrimination, good reproducibility, and an ability to detect early disease. Furthermore, we evaluated whether the sensitivity, specificity, and positive and negative predictive values of these changes could be calculated from published data. Few cohort studies of early inflammatory joint disease have been published, and the data come mainly from studies in early RA. Among radiographic alterations described to date, erosions seem associated with the best reliability and discriminating power. Radiographic alterations are of limited sensitivity for early rheumatoid arthritis because they occur only after some time. Radiographs of the hands and feet are far easier to obtain than magnetic resonance imaging and ultrasonography, which seem promising but are still undergoing validation.
13130461 Association of mortality with disease severity in rheumatoid arthritis, independent of com 2003 Sep OBJECTIVE: To measure the extent to which mortality in rheumatoid arthritis (RA) is associated with disease severity, independent of the presence of coexistent diseases (comorbidity). METHODS: We measured disease severity and comorbidity among RA patients attending scheduled appointments at a rheumatology clinic. We used the Duke Severity of Illness Checklist (DUSOI), a clinical judgment-based measure of the severity of disease. We disaggregated the DUSOI into an RA component (RADUSOI), which we used to measure RA disease severity, together with a physician-rated 10-point global RA severity assessment. We measured comorbidity using the non-RA component of the DUSOI (COMDUSOI) and using the Charlson Comorbidity Index. Patients were contacted periodically for up to 6 years, during which we recorded deaths. We estimated the effect of disease severity and comorbidity on mortality using Kaplan-Meier survival curves, Cox proportional hazards models, and logistic regression with receiver operating characteristics (ROC) curve analysis. RESULTS: The sample comprised 779 patients. Followup ranged from 0.1 year to 6.3 years (mean 2.52 years), for an observation period of 2,315 patient-years. Seventy-five patients died (9.6%), for a total mortality of 3.2 per 100 patient-years (95% confidence interval 2.6-4.1). Both disease severity and comorbidity displayed significant bivariate associations with mortality. In multivariate Cox models adjusted for age, sex, and disease duration, the RADUSOI and global RA severity scores were associated with mortality independent of either the COMDUSOI or Charlson Comorbidity scores. The area under the ROC curve for a logistic model on mortality increased from 0.79 with age, sex, and disease duration included, to 0.84 after adding RA severity and comorbidity (P < or = 0.005 for the increase in ROC area). CONCLUSION: RA disease severity is significantly associated with mortality regardless of the presence of comorbid disease. Combined with each patient's age, sex, and disease duration, information on RA severity and comorbidity allows an accurate prediction of mortality among patients with RA.
14872450 Issues in cross-cultural validity: example from the adaptation, reliability, and validity 2004 Feb 15 OBJECTIVE: Guidelines have been established for cross-cultural adaptation of outcome measures. However, invariance across cultures must also be demonstrated through analysis of Differential Item Functioning (DIF). This is tested in the context of a Turkish adaptation of the Health Assessment Questionnaire (HAQ). METHODS: Internal construct validity of the adapted HAQ is assessed by Rasch analysis; reliability, by internal consistency and the intraclass correlation coefficient; external construct validity, by association with impairments and American College of Rheumatology functional stages. Cross-cultural validity is tested through DIF by comparison with data from the UK version of the HAQ. RESULTS: The adapted version of the HAQ demonstrated good internal construct validity through fit of the data to the Rasch model (mean item fit 0.205; SD 0.998). Reliability was excellent (alpha = 0.97) and external construct validity was confirmed by expected associations. DIF for culture was found in only 1 item. CONCLUSIONS: Cross-cultural validity was found to be sufficient for use in international studies between the UK and Turkey. Future adaptation of instruments should include analysis of DIF at the field testing stage in the adaptation process.
14967062 Is there any future for tumor necrosis factor antagonists in chronic heart failure? 2004 Over the past decade, a large number of studies have demonstrated that tumor necrosis factor-alpha (TNFalpha) plays an important role in the development of heart failure. Indeed, administration of TNFalpha to experimental animals and transgenic over-expression of TNFalpha replicate the heart failure phenotype. Furthermore, attenuation of the biologic activity of TNFalpha abrogates the development of heart failure in model systems. These pre-clinical studies, suggested that anti-cytokine therapy could prove beneficial in the treatment of patients with heart failure. While early studies supported this hypothesis, anti-TNF strategies have not demonstrated salutary benefits in large, multicenter randomized and placebo-controlled clinical trials in patients with symptomatic heart failure. This finding was disappointing. However, recent studies might provide clarification of this conundrum. For example, the failure to elicit beneficial effects with anti-cytokine therapy might be explained by novel pharmacogenomic or pharmacodynamic effects, the design of the Phase III clinical trials, or discordance between animal models and the human condition. Thus, appropriately designed clinical trials and newer anticytokine agents may demonstrate benefit.
12126633 Immunization of rats with homologous type XI collagen leads to chronic and relapsing arthr 2002 May The most commonly used animal model for rheumatoid arthritis (RA) is collagen-induced arthritis (CIA), induced by immunization with type II collagen (CII), a cartilage restricted protein. In this work we show that type XI collagen (CXI), which is a minor component in cartilage, induces a different form of erosive and chronic relapsing polyarthritis in rats. Using a series of inbred rat strains involving various genetic backgrounds (DA, LEW, E3), and congenic MHC regions (a, u, f, n, c, d), we found that CXI induced arthritis (C(XI)IA) is associated with the RT1f haplotype in contrast to CII induced arthritis (C(II)IA), which is associated with the RT1a and RT1u haplotypes. The C(XI)IA follows a chronic disease course affecting peripheral joints with both progression and relapses, which appear not to cease (occurring >800 days). Susceptible strains showed a sustained antibody response to CXI with time indicating that the autoimmune response was self-perpetuated. Microscopic analysis of the joints at different stages demonstrated the severe destruction of bone and cartilage by pannus tissue consisting of activated macrophages and T cells. The main difference to joints from rats with C(II)IA was larger numbers of infiltrating lymphocytes and these tended to form follicle-like aggregates. Surprisingly, males were more susceptible to C(XI)IA than females whereas the opposite has been observed in other rat arthritis models, including C(II)IA. Taken together, C(XI)IA is a chronic relapsing and erosive polyarthritis that is MHC associated, which in fact fulfills the criteria for diagnosis of RA. Thus the C(XI)IA model will be useful as a novel and relevant animal model for RA.
12166117 [A case of rheumatoid arthritis with secondary amyloidosis in urinary bladder]. 2002 Jun We document a case of 61-year-old woman with a 24 year history of rheumatoid arthritis (RA), who developed severe polyarthralgia, dry cough, paresthesia in the legs, frequent micturition, and severe macrohematuria. We diagnosed as severe RA with extraarticular manifestations based on interstitial pneumonia, mononeuritis multiplex, subcutaneous nodules, and high titer of rheumatoid factor. Ultrasonography demonstrated an intravesical mass lesion. A histological examination of the urinary bladder by endoscopic biopsy revealed marked deposition of AA amyloid. The diagnosis of secondary amyloidosis and bacterial cystitis were made based on histological findings and urine culture. At first, we administered antibiotics by intravenous infusion, which resulted in cure of cystitis and partial improvement of macrohematuria. Then combination therapy of corticosteroids and cyclophosphamide successfully reduced the disease activity of RA. There have only been a few reports published so far on the vesical amyloidosis in patients with RA. However, 5 of 10 patients (50%) in vesical amyloidosis died because of continuous massive hematuria, which induced disseminated intravascular coagulation and multiple organ failure. In conclusion, secondary amyloidosis of the urinary bladder should be considered as a possible cause of hematuria in patients with long-term RA and as an important prognosis factor of RA.
12355476 Predictors of infection in rheumatoid arthritis. 2002 Sep OBJECTIVE: Patients with rheumatoid arthritis (RA) have been shown to have an increased susceptibility to the development of infections. The exact causes of this increased risk are unknown, but may relate to immunologic disturbances associated with the disease or to the immunosuppressive effects of agents used in its treatment. This study was undertaken to identify predictors of serious infections among patients with RA. Identification of such factors is the necessary first step in reducing the excess risk of infection in RA. METHODS: Members of a population-based incidence cohort of Rochester, Minnesota residents ages >or=18 years, who had been diagnosed with RA between 1955 and 1994, were followed up longitudinally through their complete medical records until January 1, 2000. We examined potential risk factors for the development of all objectively confirmed (by microbiology or radiology) infections and for infections requiring hospitalization. Potential risk factors included RA severity measures (rheumatoid factor positivity, elevated erythrocyte sedimentation rate, extraarticular manifestations of RA, and functional status), comorbidities (diabetes mellitus, alcoholism, and chronic lung disease), and other risk factors for infection (presence of leukopenia, smoking). Predictors were identified using multivariate time-dependent Cox proportional hazards modeling. RESULTS: The 609 RA patients in the cohort had a total followup time of 7,729.7 person-years (mean 12.7 years per patient). A total of 389 patients (64%) had at least 1 infection with objective confirmation, and 290 (48%) had at least 1 infection requiring hospitalization. Increasing age, presence of extraarticular manifestations of RA, leukopenia, and comorbidities (chronic lung disease, alcoholism, organic brain disease, and diabetes mellitus), as well as use of corticosteroids, were strong predictors of infection (P < 0.004) in both univariate and multivariate analyses. Notably, use of disease-modifying antirheumatic drugs was not associated with increased risk of infection in multivariate analyses, after adjustment for demographic characteristics, comorbidities, and disease-related variables. CONCLUSION: We identified a number of strong predictors of infections in a population-based cohort of patients with RA. These results can be used to prospectively identify high-risk patients, who may benefit from closer followup and implementation of preventive strategies.
15577086 [Joint destruction and matrix metalloproteinases--regulation by pharmacologic inhibitors a 2004 Jul Matrix metalloproteinase (MMP) plays an important role in degradation of cartilage matrix. The expression of MMPs in cartilage or syovial membrane was increased in osteoarthritis or rheumatoid arthritis. We summarized the regulation mechanism of MMP production, and described pharmacologic inhibitors such as non steroidal anti-inflammatory drugs, steroid and growth factors, which might be useful to prevention of joint destruction.
14508645 [Arthroplasty of the metacarpophalangeal joint using pyrocarbonate implants]. 2003 Sep As early as the 1970s, pyrocarbon became a point of focus in the search for materials for alternative finger replacement. This type of material had already proven its biocompatibility and excellent wear behaviour in its use for artificial heart valves. The first trials with pyrocarbon surface replacement implants for the small finger joints in baboons showed good biocompatibility as well as good functional results. The first patient series confirmed theses results in long-term follow-up. Meanwhile, the surface replacement implants made of pyrocarbon are an interesting alternative to silicon spacers. Further developments for other joints in the hand are under evaluation.
12510359 [Pharmacogenetics of disease modifying anti-rheumatic drugs]. 2002 Dec There are large differences in the effectiveness of disease modifying anti-rheumatic drugs(DMARD) from one person to the next. Adverse drug reactions caused by DMARD can also occur to some patients, but do not occur to others. One possible cause of the differences in the effectiveness and adverse drug reactions is genetic variation in how individuals metabolize drugs. The Human Genome Project heralds new opportunities for using information about genetic variation to predict responses to drug therapies, called pharmacogenetics. Based on pharmacogenetics, tailor-made drug therapy is going to be realized. Our recent studies revealed the relationship between genetic polymorphisms of drug metabolizing enzymes and the efficacy of methotrexate or sulfasalazine in patients with rheumatoid arthritis, suggesting pharmacogenetics is applicable to the treatment of rheumatoid arthritis.
12417052 Angiogenesis and chemokines in rheumatoid arthritis and other systemic inflammatory rheuma 2002 Jul Angiogenesis, the formation of new vessels, is important in the pathogenesis of rheumatoid arthritis (RA) and other inflammatory diseases. Chemotactic cytokines termed chemokines mediate the ingress of leukocytes, including neutrophils and monocytes into the inflamed synovium. In this review, authors discuss the role of the most important angiogenic factors and angiogenesis inhibitors, as well as relevant chemokines and chemokine receptors involved in chronic inflammatory rheumatic diseases. RA was chosen as a prototype to discuss these issues, as the majority of studies on the role of angiogenesis and chemokines in inflammatory diseases were carried out in arthritis. However, other systemic inflammatory (autoimmune) diseases including systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Sjögren's syndrome (SS), mixed connective tissue disease (MCTD), polymyositis/dermatomyositis (PM/DM) and systemic vasculites are also discussed in this context. As a number of chemokines may also play a role in neovascularization, this issue is also described here. Apart from discussing the pathogenic role of angiogenesis and chemokines, authors also review the regulation of angiogenesis and chemokine production by other inflammatory mediators, as well as the important relevance of neovascularization and chemokines for antirheumatic intervention.
12659823 Regional musculoskeletal conditions: foot and ankle disorders. 2003 Feb Foot pain is very common, especially in women, owing to inappropriate footwear. Overuse, repetitive strain and minor, easily forgettable injuries may result in chronic foot and ankle pain. Rheumatoid arthritis, spondyloarthropathies and gout frequently affect the foot, often as a first presentation. Charcot's joints and foot infections are not rare in diabetes. The rheumatologist should be familiar with foot disorders, either localized or as manifestations of generalized disease. History taking, physical examination, identification of the source of pain by intra-articularly given local anaesthetics and imaging methods should be used to reveal the underlying disorder. Correct diagnosis and efficient therapy-including local steroid injections, physiotherapy, orthoses, surgery-are necessary not only for treatment but also for preventing biomechanical chain reactions. This chapter gives an overview of the epidemiology, diagnosis and treatment of foot pain and foot disorders caused by both local and generalized diseases.
12794790 Development of a work instability scale for rheumatoid arthritis. 2003 Jun 15 OBJECTIVES: To explore the concept of work instability (WI), a state in which the consequences of a mismatch between an individual's functional abilities and the demands of his or her job could threaten continuing employment if not resolved, in people with rheumatoid arthritis (RA). To develop the Work Instability Scale (WIS). METHODS: WI in people with RA was explored through qualitative interviews, which were then used to generate items for the WIS. RESULTS: Through Rasch analysis and validation against a gold standard of expert vocational assessment, a short 23-item, self administered, RA WIS was developed. CONCLUSION: The WIS can be scored in 3 bands indicating low, medium, and high risk of work disability.
14969047 The histopathology of early synovitis. 2003 Sep Early diagnosis and therapeutic intervention are needed to prevent the morbidity related to erosive arthropathies such as rheumatoid arthritis (RA), yet it is difficult to distinguish various forms of synovitis early in the disease course. The availability of synovial tissue biopsy techniques has facilitated the analysis of synovial tissue from patients with early disease. Comparison of the histopathologic features of synovial tissue in early RA, established RA, and in non-RA synovitis has shown subtle, but potentially important differences in histologic features, cytokine and protease expression patterns, and apoptosis. Ultimately, it remains to be shown definitively that analysis of the histopathological features of synovial tissue early in disease is of independent value in identifying patients destined to have persistent synovitis or erosive disease, and in turn, in allocating patients to specific therapeutic strategies.
14617033 Single-nucleotide polymorphisms of the interleukin-18 gene promoter region in rheumatoid a 2003 Dec Rheumatoid arthritis (RA) is a chronic arthritic condition that can lead to deformities and disabilities. Although numerous studies reported the association of human leukocyte antigen (HLA)-DRB1*04 and RA, other genes, e.g. cytokines genes, may contribute towards disease susceptibility. Interleukin-18 (IL-18) is a proinflammatory cytokine postulated to play a role in the acute and chronic inflammatory phases of RA. The IL-18 protein expression seems to be regulated by two single-nucleotide polymorphisms (SNPs) located at positions -607 and -137 in the promoter region of the gene. It is postulated that specific alleles may be associated with susceptibility to the development of RA. In the present study, we described the IL-18 gene promoter region genotypes and combined genotypes (-607/-137) in 106 RA patients and 273 unrelated healthy controls to evaluate the contributions of these alleles to RA predisposition in Chinese, Malays, and Indians. The genotyping were performed using sequence-specific polymerase chain reactions. Rheumatoid factors were assayed by enzyme-linked immunosorbent assay. Biodata were obtained through chart review. The controls had significantly higher frequency of AA genotype at position -607 when compared to RA patients. No significant differences were observed in the distribution of either allelic or genotypic frequencies at position -137. There was no association between the genotypes and the presence of rheumatoid factors. This study did not find evidence of a genetic susceptibility factor but demonstrated the novel finding that the AA genotype at position -607 is associated with a protective effect against development of RA in Chinese individuals. This protection may be mediated through inhibition of cyclic (Adenosine 3', 5'-cyclic monophosphate) AMP-responsive element (CRE)-binding protein by the disruption of the CRE consensus sequence.
12508766 Impaired glutathione reductase activity and levels of collagenase and elastase in synovial 2002 Nov OBJECTIVE: To test the activity of elastase, collagenase and glutathione reductase in the synovial fluid (SF) of patients with rheumatoid arthritis (RA) and in patients with osteoarthritis (OA); to correlate the elastase and collagenase activity with the glutathione reductase activity, which is important for the inactivation of oxygen free radicals. METHODS: 24 patients affected by osteoarthrosis and 24 patients affected by rheumatoid arthritis took part in the study. We measured elastase activity towards the substrate metoxysuccinyl-alanyl-alanyl-prolyl-valyl-p-nitroanilide (MeOSuc-ala-ala-proval-p-NA) which is highly specific for elastase, and insensitive to the other serine proteases, such as cathepsin G; collagenase activity was measured using [14C]-acetylated collagen as the substrate. Glutathione reductase activity was measured following the oxidation of nicotinamide adenine dinucleotide phosphate reduced (NADPH) in the presence of oxidized glutathione (GSSG). RESULTS: The concentrations of elastase, collagenase and glutathione reductase were statistically higher in patients with RA than in patients with OA. Moreover, in the SF of patients with RA we found positive correlation between enzyme activity levels. CONCLUSION: These results confirm a high activity of collagenase and elastase in the SF of patients with RA, which is about 30 times higher than that found in the SF of patients with OA. These data underline the synergic action of these enzymes in the pathogenesis of joint damage. RA patients also exhibit higher levels of glutathione reductase, which is important for the detoxification pathway of oxygen free radicals. However, compared with findings for collagenase and elastase, the increase in glutathione reductase is only three times higher than level found in the SF of OA patients. The limited increase in glutathione reductase activity during the inflammatory process might lead to an insufficient protective effect at the joint level in rheumatoid arthritis.
15146411 Midkine, a heparin-binding growth factor, is fundamentally involved in the pathogenesis of 2004 May OBJECTIVE: Midkine (MK), a heparin-binding growth factor, promotes growth, survival, and migration of various cells. The essential role of MK in migration of inflammatory cells has been shown using mice deficient in the MK gene (Mdk(-/-) mice). We undertook this study to investigate the role of MK in the pathogenesis of rheumatoid arthritis (RA). METHODS: MK levels in specimens from patients were determined by enzyme-linked immunosorbent assay, and localization of MK was revealed by immunohistochemical analysis. Susceptibility to antibody-induced arthritis was compared between Mdk(-/-) and wild-type (WT) mice. Osteoclast differentiation was monitored using macrophage-like cells isolated from human synovial tissue and macrophages from mouse bone marrow. RESULTS: MK levels in sera and synovial fluid were increased in most RA patients, indicating a strong correlation between MK expression and RA. MK was expressed in macrophage-like cells and fibroblast-like cells in synovial membranes from the patients. In antibody-induced arthritis, Mdk(-/-) mice seldom developed the disease, while most of the WT mice did. Administration of MK to the Mdk(-/-) mice increased the frequency of antibody-induced arthritis. Migration of inflammatory leukocytes to the synovial membranes in the disease model was suppressed in the Mdk(-/-) mice. Furthermore, MK was found to promote the differentiation of osteoclasts from macrophages. CONCLUSION: MK participates in each of the two distinct phases of RA development, namely, migration of inflammatory leukocytes and osteoclast differentiation, and is a key molecule in the pathogenesis of RA.
15164093 Targeting cathepsin L (CL) by specific ribozymes decreases CL protein synthesis and cartil 2004 Jul The present study was undertaken to examine whether ribozymes cleaving specifically cathepsin L (CL) mRNA are able to decrease the synthesis of CL protease in rheumatoid arthritis synovial fibroblasts (RA-SF) and thereby reduce the invasiveness into cartilage both in vitro and in the SCID mouse coimplantation model of RA. Two different ribozymes that cleave CL mRNA specifically at positions 533 (RzCL533) and 790 (RzCL790) were generated. Using retroviral gene transfer, RA-SF were transduced with the ribozyme constructs or the empty vector. To examine the effect of the ribozymes on the mRNA level, quantitative analysis for CL mRNA was performed using real-time PCR. For evaluation on the protein level, ELISA using specific anti-CL antibodies was performed. In addition, transduced RA-SF were examined in vitro in a three-dimensional destruction assay evaluating their ability to degrade extracellular matrix produced by human chondrocytes. Matrix destruction was monitored by the release of soluble glycosaminoglycans (sGAG). Using the in vivo SCID mouse coimplantation model of RA, RzCL533-transduced RA-SF and control cells were coimplanted with human cartilage for 60 days. After being killed, invasion of RA-SF into the cartilage was evaluated by using a semiquantitative score. Transduction of RA-SF with RzCL533 and RzCL790 ribozymes decreased significantly the expression of CL mRNA to 44% (range 25-62%) and 20% (range 1-43%), respectively, when compared to mock-transduced cells. The protein concentration of CL in the cell culture supernatants of transduced RA-SF was decreased from 16.0 ng/ml in the mock constructs to 4.1 and 8.2 ng/ml (mean), respectively. Using the in vitro cartilage destruction assay, the release of sGAG decreased to 46 and 60%, respectively, after 14 days when compared to mock-transduced cells. In the SCID mouse coimplantation model of RA, RzCL533-transduced RA-SF revealed a significant lower cartilage invasion when compared to mock and untransduced cells. Using retroviral gene transfer, ribozymes cleaving CL mRNA inhibit specifically the synthesis of this matrix-degrading enzyme and reduce cartilage destruction in in vitro and in vivo models. Our study therefore suggests that ribozymes targeting CL could be a novel and efficient tool to inhibit joint destruction in RA.