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ID PMID Title PublicationDate abstract
9640132 Inactivation of antithrombin III in synovial fluid from patients with rheumatoid arthritis 1998 Mar OBJECTIVE: To investigate the thrombin inhibitory capacity of antithrombin III in the inflamed human joint. METHODS: Thrombin inhibitory capacity was measured, using a kinetic spectophotometric method, in matched plasma and synovial fluid samples of patients with rheumatoid arthritis (n = 22) and osteoarthritis (n = 16), together with normal control plasma samples (n = 13). In the same samples, the concentration of antithrombin III was also determined by the method of radial immunodiffusion. The combination of these measurements allowed the calculation of the specific thrombin inhibitory capacity of these samples. RESULTS: An increased concentration of antithrombin III in rheumatoid compared with osteoarthritic synovial fluid was noted (p < 0.05). However, there was a significant depression in the specific activity of antithrombin III in rheumatoid synovial fluid when compared with matched plasma samples (p < 0.001) or with osteoarthritic synovial fluid (p < 0.05). CONCLUSION: In rheumatoid synovial fluid the thrombin inhibitory capacity of antithrombin III is disproportionately depressed relative to the concentration of antithrombin III, indicating the inactivation of antithrombin III in the rheumatoid joint.
10852985 Methotrexate as a preferential cyclooxygenase 2 inhibitor in whole blood of patients with 2000 May OBJECTIVE: To investigate the regulation of whole-blood cyclooxygenase-1 and -2 (COX-2 and COX-1) activities by methotrexate (MTX) in rheumatoid arthritis (RA) patients. METHODS: Whole blood was withdrawn from nine healthy volunteers, 12 RA patients treated with MTX (RA/MTX) and six RA patients treated with chloroquine (RA/CQ). COX-1 activity was quantified as platelet thromboxane B(2) production in unstimulated blood and COX-2 activity was measured as prostaglandin E(2) (PGE(2)) production in whole blood stimulated with LPS. Thromboxane B(2) and PGE(2) were measured by radioimmunoassay. We studied the drug effect in vitro by direct incubation of MTX with blood obtained from normal donors. Ex vivo assays were performed with blood collected from RA/MTX and RA/CQ patients. The influence of serum factors on enzyme activities was analysed in blood collected from normal donors and incubated with RA/MTX, autologous or heterologous serum. RESULTS: In vitro assays showed no direct action of MTX on the activity of either enzyme. Assays performed with blood from RA/MTX patients showed preferential inhibition of COX-2 activity (PGE(2) = 10.11 +/- 2.42 ng/ml) when compared with blood of normal donors (PGE(2) = 37.7 +/- 4.36 ng/ml; P = 0.001). Inhibition of COX-2 activity was also observed when blood of normal donors was co-incubated with RA/MTX serum. CONCLUSION: Our results clearly show that the anti-inflammatory action of low-dose MTX is partly mediated by a serum factor induced by MTX or a MTX metabolite that preferentially inhibits the activity of COX-2.
9115749 Hepatocyte growth factor in bronchoalveolar lavage fluids and cells in patients with infla 1997 Apr Pulmonary fibrosis is a chronic inflammatory disorder characterized by diffuse fibrous remodeling of alveolar spaces. Although much interest is focused on mechanisms of the inflammatory process in pulmonary fibrosis, little is known about the repair and regenerative process. Hepatocyte growth factor (HGF), originally discovered as a mitogen for hepatocyte regeneration, is now recognized as a multifunctional mesenchymal factor for epithelial regeneration, including the regeneration of alveolar type II epithelial cells. Involvement of HGF and its receptor (c-met) is evident in animal models of acute lung injury produced by hydrochloride inhalation. We studied the role of HGF in patients with idiopathic pulmonary fibrosis (IPF) (25 cases), lung fibrosis associated with rheumatoid arthritis (22 cases), and sarcoidosis (39 cases). Immunohistochemical evaluation demonstrated that hyperplastic alveolar type II epithelial cells, as well as alveolar macrophages, were strongly stained with anti-HGF antibody in tissues of patients with IPF. The concentration of HGF in bronchoalveolar lavage fluid (BALF) was significantly higher than in normal controls (0.23 +/- 0.09 pg/microg) in patients with IPF (0.77 +/- 0.88 pg of HGF/microg of albumin, P < 0.001), lung fibrosis associated with rheumatoid arthritis (0.50 +/- 0.64 pg/microg, P < 0.01), and sarcoidosis (0.41 +/- 0.61 pg/microg, P < 0.05). In situ hybridization revealed mRNA for HGF in alveolar macrophages (especially small monocytelike macrophages). These results indicate that the increase in HGF concentration in patients' peripheral air spaces is due to augmented HGF production by alveolar epithelial cells and alveolar macrophages. HGF, through a paracrine mechanism, may play an important role in the repair and healing of the inflammatory lung damage in pulmonary fibrosis.
9347237 Rheumatoid neutrophilic dermatitis. 1997 Oct Rheumatoid neutrophilic dermatitis (RND) is a rare cutaneous finding in patients with severe rheumatoid arthritis or with high-titer rheumatoid factors. Most commonly, these lesions are erythematous papules or plaques distributed symmetrically on extensor surfaces. On histologic examination a dense dermal neutrophilic infiltrate without vasculitis is apparent. The pathogenesis of RND is unclear, and few treatments are known. With careful clinical and histologic examination, RND may be differentiated from the wide array of other cutaneous findings in rheumatoid arthritis.
10084035 The effects of recombinant human erythropoietin on autologous blood donation in rheumatoid 1999 Jan OBJECTIVES: The effect of recombinant human erythropoietin (rHuEPO) treatment on autologous blood donation was evaluated in anaemic patients with rheumatoid arthritis (RA) undergoing total joint replacement surgery. METHODS: A total of 56 total knee or hip joint replacement operations were performed in the knee or hip joint in 36 anaemic RA patients (hemoglobin (Hb) concentration < 11.0 g/dl]. All of the patients received intravenous rHuEPO at a dose of 100-200 units/kg body weight three times a week for 3 weeks. An autologous blood donation of 800-1200 g was the goal for each patient. A refractory case was defined as a patient whose Hb level did not increase to 10.0 g/dl after 3 weeks of treatment with rHuEPO. The objective signs of arthritis were assessed by the Lansbury activity index (AI). During the treatment period, the patients underwent weekly hematological analyses, including routine hematology, serum iron, serum ferritin, C-reactive protein (CRP), and serum erythropoietin levels. RESULTS: The response to rHuEPO treatment was determined, and blood donation was possible in 47 of 56 joint replacements. In the other 9 operations, donation was not possible due to a poor response to rHuEPO. The mean Hb level before treatment in the refractory group (8.3 g/dl) was significantly lower than that in the responsive group (10.4 g/dl, p = 0.0002). During the treatment period, the mean erythropoietin level was above the normal limit in the refractory group. The mean AI for the refractory group tended to be lower than that in the responsive group. The mean pre-treatment CRP (6.4 mg/dl) and erythrocyte sedimentation rate (ESR) (87.1 mm/h) levels in the refractory group were significantly higher than those in the responsive group (CRP: 3.2 mg/dl, p = 0.008, ESR: 52.6 mm/h, p = 0.01). CONCLUSIONS: The control of disease activity prior to rHuEPO treatment is considered to a prerequisite for autologous blood donation. In addition, severe anaemia (Hb concentration < 8.0 g/dl) appears to be another risk factor for refractoriness to rHuEPO treatment with the present protocol. A higher rHuEPO dose (> 200 units/kg/3 times a week for three weeks) was considered to be necessary in the refractory group.
11321825 [A case of rheumatoid lung disease in which lung involvement preceded arthritis]. 2001 Feb A 75-year-old man was admitted because of dyspnea on exertion and diffuse pulmonary interstitial shadows. An open lung biopsy revealed unclassified interstitial pneumonia. The abnormal shadow subsided spontaneously. Three years later, however, rheumatoid arthritis developed with a simultaneous relapse of interstitial pneumonitis, which was alleviated by steroid therapy. We report here the rheumatoid lung disease that preceded the onset of arthritis, together with a review of the literature.
11139202 Use of two-dimensional gel electrophoresis to measure changes in synovial fluid proteins f 2001 Jan Synovial fluid proteins from microliter volumes of synovial fluid were resolved by two-dimensional polyacrylamide gel electrophoresis and detected by silver staining to investigate the feasibility of using two-dimensional (2D) electrophoresis in the clinical research setting and provide global disease information of disease progression. Several hundred proteins could be resolved as spots, many of which displayed the characteristic pattern of plasma-derived glycoproteins. The lowest level of detection was approximately 0.2 ng from a total of 50 microg of protein loaded. Most of the proteins could be identified on the basis of pI and molecular weight when compared with plasma protein maps on the World Wide Web. Unknown proteins were characterized by mass spectrometry of tryptic digests and by comparison with peptide databases. Synovial fluids from patients with rheumatoid arthritis were analyzed using this technique. Each subject received a fixed dose of antibody to CD4 as part of a phase II clinical trial to determine the efficacy of this immunosuppressive treatment in modifying disease activity. Synovial fluid was removed at day 0, followed by administration of antibody. Subsequent removal of synovial fluid and additional administration of antibody were carried out at different times thereafter. Changes in levels of acute-phase proteins were quantified by densitometry of silver-stained 2D polyacrylamide gels. Other parameters of disease progression such as serum C-reactive protein and physician's global assessment of clinical condition were used for comparison. In this way, changes in acute-phase proteins towards normal levels, as measured by 2D polyacrylamide gel electrophoresis, could be correlated with clinical improvement and conventional clinical chemistry measurements. Thus, the system can be used for quantitative analysis of protein expression in sites of autoimmune disease activity such as the synovial fluid of rheumatoid arthritis patients.
9704648 Asymptomatic synovitis precedes clinically manifest arthritis. 1998 Aug OBJECTIVE: It has been hypothesized that asymptomatic synovitis may precede clinical manifestations of arthritis in the earliest phase of rheumatoid arthritis (RA). To obtain more insight into this disease phase, we investigated the immunohistologic features of synovial tissue (ST) from the knee joints of rhesus monkeys with induced arthritis and from RA patients with both clinically involved and clinically uninvolved knee joints. METHODS: Serial ST biopsy specimens from the knee joints of 4 rhesus monkeys that had been immunized with type II collagen and ST from 10 RA patients were investigated. Eight patients without inflammatory joint disease served as controls. RESULTS: In ST from immunized monkeys, an influx of macrophages was observed well before the occurrence of arthritis. Signs of inflammation were also demonstrated in ST from clinically uninvolved knee joints of all RA patients evaluated. The ST was characterized in particular by infiltration with macrophages and by the expression of macrophage-derived cytokines. CONCLUSION: The findings support the view that asymptomatic synovitis precedes clinically manifest arthritis in both early and established RA. This implies that the debut of RA already represents a chronic phase of the disease.
10853555 [Vascular neuropathies]. 2000 Apr 1 Vasculitic neuropathy is an important cause of peripheral neuropathy because of its potentially severe prognosis and an early recommended therapy. Diagnosis is easy when the clinical presentation is an acute, painful, multiple mononeuropathy but more difficult when presenting as a polyneuropathy. Electrophysiologic studies play an important role in the diagnosis. Muscle and nerve biopsies confirm the vasculitic process and demonstrate ischemic neuropathy lesions. Polyarteritis nodosa, rheumatoid arthritis and non-systematic vasculitic neuropathy are the main conditions of vasculitic neuropathy. Usual treatment includes a combination of corticosteroids and cyclophosphamide.
11330759 Walking ability as a measure of treatment effect in early rheumatoid arthritis. 2001 Apr OBJECTIVE: To assess the clinical usefulness of a prototype walkmat system in patients with early rheumatoid arthritis (RA). SUBJECTS: Twenty-four subjects with early RA and symptomatic forefoot disease requiring therapy with second-line drugs were recruited. DESIGN: Each subject underwent clinical assessment together with gait analysis on the contact sensitive walkmat system and Kistler forceplate before and after six months of treatment with second-line drugs. Two subjects were lost to follow-up. RESULTS: There was the expected improvement in disease activity in response to therapy. Significant differences were also demonstrated in defined gait parameters that indicated improved weight-bearing and enhanced forefoot propulsion. CONCLUSION: Medical therapy improved walking ability in patients with RA and the walkmat system provided a useful adjunct to existing outcome measures in the assessment of lower limb function.
11235775 Do the HLA-DQ and DP genes play a role in rheumatoid arthritis? 2001 Feb Whereas the DRB1 alleles have well-established associations with rheumatoid arthritis (RA), the DQ and DP alleles are of more controversial relevance to RA. Early studies of the DQB1 genes in RA determined the frequencies of the two DQB1*03 subtypes that are in linkage disequilibrium with DR4, DQB1*0301 (DQw7) and *0302 (DQw8). Their results are conflicting and difficult to interpret because molecular biology techniques for determining DR4 specificity polymorphism were not available at the time. None of the more recent studies found compelling evidence that the DQB1 alleles influenced the susceptibility to RA. A few studies suggest that the DQ alleles may influence the clinical or biological expression of the disease, perhaps through a complementary effect of the DRB1 and DQB1 alleles. DR-DQ complementarity has been demonstrated in the DQ8 transgenic mouse model, although this is not necessarily relevant to the human disease. The role of DPB1 remains hypothetical but may involve an influence of some alleles in relatively mild forms of RA. The DQB1 and DPB1 alleles are in strong linkage disequilibrium with the DRB1 alleles, making the elucidation of their independent effects a challenging task. Studies are needed to determine whether these linkage disequilibriums can influence the development of autoimmune diseases.
9167926 Pedodynographic measurements after forefoot reconstruction in rheumatoid arthritis patient 1997 May From January 1987 to December 1992, 38 patients (59 feet) with rheumatoid arthritis underwent reconstruction of the forefoot using Keller-Lelièvre arthroplasty of the first metatarsophalangeal joint and Hoffman resection of the lesser metatarsal heads. The average age of the patients was 61.3 years, with both feet involved in 21 patients and 17 with single foot involvement. The aim of our study was to evaluate the results both on a functional and an objective basis using dynamic and static pedodynographic measurements. Attention was given to dynamic pressure measurements under the metatarsal heads, the center of pressure distribution, gait analysis, and peak loads taken on different areas of the forefoot during normal walking. Correlations were made between these measurements and symptoms. After a mean follow-up time of 35 months, the clinical results were satisfactory in 54%, satisfactory with some reservations in 39%, satisfactory with major reservations in 3%, and unsatisfactory in 3% of patients.
10568424 Mortality in early "sawtooth" treated rheumatoid arthritis patients during the first 8-14 1999 OBJECTIVE: To describe mortality in a cohort of early RA patients treated from the onset with disease-modifying antirheumatic drugs (DMARDs) according to the 'sawtooth' strategy. PATIENTS AND METHODS: A total of 135 early RA patients were followed up for 8-14 years or until death. Causes of death were checked on the death certificates and in patient files. Standardized mortality ratio (SMR) was calculated. Results. A total of 25 (14F, 11M) patients died during the 1422 person-years of follow-up. The SMR (95%CI) was 1.28 (0.83-1.89); 1.69 (0.92-2.82) for women and 0.98 (0.49-1.74) for men. In five cases death was closely related to RA. No one died from amyloidosis. Not a single death was caused by DMARDs in spite of extensive use of these drugs. Patient's age at the start was the only statistically significant predictor for death. CONCLUSION: Despite active treatment with available DMARDs, RA seems still to be a fatal disease in a proportion of cases.
11728228 Gene therapy for rheumatoid arthritis. 2001 Nov Rheumatoid arthritis (RA) is a disabling, painful disorder affecting 1% of the world's population. Although the aetiology of RA remains unknown, recent advances in understanding its pathophysiology have led to the characterisation of several proteins whose activities may be anti-arthritic. Clinical application of such proteins has greatly improved the treatment of RA, but the disease remains incurable and difficult to manage in a substantial number of patients. Thus, there are continued efforts to develop new therapeutic strategies. Because RA is a chronic condition, effective treatment will probably require the presence of therapeutic agents for extended periods of time. In the case of proteins, this is problematic. Gene therapy may offer a solution to this problem. Experimental studies have confirmed the feasibility, efficacy and safety of gene therapy for the treatment of animal models of arthritis. Several different approaches have shown promise in this regard, including gene transfer to the synovial lining cells of individual joints and the systemic delivery of genes to extra-articular locations. One unexpected finding has been the 'contralateral effect' in which gene delivery to one joint of an animal with polyarticular disease leads to improvement of multiple joints. Investigation of this phenomenon has led to interest in cell trafficking and the genetic modification of antigen-presenting cells (APC). The first Phase I clinical trial tested the feasibility and safety of ex vivo gene transfer to the synovial lining of human joints. This clinical trial has been successfully completed and two other Phase I trials are in progress. A Phase II study is now being planned to investigate the efficacy of gene transfer to the joints of patients with early stage RA.
11407683 Change in bone mineral density in patients with rheumatoid arthritis during the first deca 2001 Jun OBJECTIVE: Rheumatoid arthritis (RA) has been reported to be associated with bone loss during the first years of the disease. The magnitude of this problem after the initial years has not yet been evaluated. In the present study, the change in bone mineral density (BMD) in patients with recent-onset RA as well as the effects of inflammation, mobility, and the use of prednisone on this change were studied in the first decade of the disease. METHODS: BMD was measured twice in 76 RA patients with mean disease durations of 2.35 years at the first BMD measurement and 8.90 years at the second BMD measurement. BMD was measured in both hips using dual x-ray absorptiometry. Results were expressed as mean +/- SEM Z scores (using age- and sex-matched reference values) and as mean +/- SEM percent change in BMD (in gm/cm2) per year. The effects of inflammation, mobility, and the use of prednisone on change in BMD were evaluated using multiple linear regression analyses. RESULTS: At the first BMD measurement, RA patients had lower BMD compared with the reference values (Z score -0.42+/-0.11, 95% confidence interval [95% CI] -0.64, -0.20). Between the 2 measurements, we observed a small decrease in BMD of -0.28+/-0.11%/year (95% CI -0.07 to -0.49). However, the rate of bone loss was smaller than expected. The Z score increased by 0.13+/-0.05 between the 2 BMD measurements (95% CI 0.02, 0.23). Only the use of prednisone was significantly associated with increased bone loss. In a separate analysis that included only postmenopausal women, increased physical activity and longer time since menopause were both associated with decreased bone loss. In this subgroup of patients, the use of prednisone was significantly associated with increased bone loss as well. A high erythrocyte sedimentation rate was associated with increased bone loss, but this did not reach statistical significance. CONCLUSION: After the initial years of the disease, bone loss in RA patients is lower than expected compared with age- and sex-matched reference values. Postmenopausal RA patients with low levels of physical activity are at increased risk of losing bone. Use of prednisone was the only variable consistently associated with reduction in BMD in RA patients.
10483268 [The association between autoimmune thyroid diseases and rheumatic diseases: a review]. 1999 Aug Although the association between autoimmune thyroid diseases (especially Graves' and Hashimoto's diseases) and rheumatic diseases has been well accepted, its precise mechanism is unclear. Autoreactive T cells may recognize autoantigens not only those expressed on thyroid but also those on other organs. Rheumatoid arthritis and psoriatic arthritis are among the examples of that suggested to occur with high incidence in association with positive anti-thyroid autoantibodies. Systemic lupus erythematosus and systemic sclerosis are also known to often coincide with autoimmune thyroid disease. Anticardiolipin antibody is suggested to be induced in the patients with thyroid autoimmunity. Overall, it would be important to analyze the pathogenic autoimmune response at the molecular level to further understand the relationship between thyroid and rheumatic autoimmune diseases.
11600989 Office-based arthroscopic synovectomy of the wrist in rheumatoid arthritis. 2001 Oct We present an office-based technique for performing arthroscopic synovectomy of the wrist in patients with rheumatoid arthritis. Intra-articular anesthesia as well as subcutaneous portal anesthesia are used. Standard portals are used in the radial carpal and midcarpal joints. Standard instrumentation is used and the synovectomy is accomplished using a motorized shaver. We performed 30 procedures in 21 patients: 15 complete synovectomies, 3 radioulnar carpal synovectomies because of only limited disease, and 12 limited synovectomies because these patients were participants in a clinical trial and required only limited synovectomy for investigational purposes. There were no complications. Office-based arthroscopic synovectomy of the wrist in patients with refractory rheumatoid arthritis can be performed safety and effectively. This technique is useful in both a clinical as well as a research setting.
10197051 DR (MHC class II) ligands: an approach to rheumatoid arthritis therapeutics. 1998 Oct The presentation of peptide antigens to T-cells by MHC Class II proteins is a central process in cellular and humoral immune responses. Blockade of this presentation event via synthetic ligands that bind to disease-associated MHCs (such as DR1 and DR4) may be useful for the treatment of autoimmune diseases such as rheumatoid arthritis, Type 1 diabetes, multiple sclerosis, lupus erthymatosis and Graves disease. Recently reported synthetic ligands for DR1 and DR4 are short modified peptides (2-7 mers) capable of competing at nanomolar concentrations with antigenic peptides for the DR (MHC) binding groove.
9858446 Diagnostic confusion caused by hepatitis C: hemochromatosis presenting as rheumatoid arthr 1998 Dec We describe a patient with hemochromatosis and coexistent infection with the hepatitis C virus who was initially thought to have rheumatoid arthritis. His symptoms began at the age of 44 with pain of the hand joints, shoulders, hips, and knees and a positive rheumatoid factor. Four years later, he required replacement of both hips due to severe hip arthritis. Abnormalities in liver function were noted early on, but they were attributed to infection with the hepatitis C virus, detected serologically and by polymerase chain reaction amplification in the blood. The correct diagnosis was delayed until a decision to use methotrexate as treatment for his arthritis led to a liver biopsy, which revealed increased iron deposition consistent with hemochromatosis, confirmed by genetic testing, which revealed that the patient was homozygous for the C282Y mutation of the HLA-H gene.
10497642 Auto--antibodies to DNA in the sera of Nigerians attending a rheumatic diseases clinic. 1998 Sep The presence of auto-antibodies to DNA in the sera of 199 Nigerians: 46 with osteoarthritis, 16 with rheumatoid arthritis, 5 with SLE, 18 with chronic hepatitis, 24 peptic ulcer disease and 90 blood donors were assayed using a haemagglutination method. The positivity rates of auto-antibodies to DNA in these subjects were comparable [X2 = 1.56, P > 0.10]. The results of this study shows that the presence of auto-antibodies to DNA is not a reliable diagnostic index for auto-immune phenomena.