Fitzgerald factor (high molecular weight kininogen) clotting activity in human plasma in health and disease in various animal plasmas.
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Fitzgerald factor (high molecular weight kininogen) is an agent in normal human plasma that corrects the impaired in vitro surface-mediated plasma reactions of blood coagulation, fibrinolysis, and kinin generation observed in Fitzgerald trait plasma. To assess the possible pathophysiologic role of Fitzgerald factor, its titer was measured by a functional clot-promoting assay. Mean +/- SD in 42 normal adults was 0.99+/-0.25 units/ml, one unit being the activity in 1 ml of normal pooled plasma. No difference in titer was noted between normal men and women, during pregnancy, or after physical exercise. Fitzgerald factor activity was significantly reduced in the plasmas of eight patients with advanced hepatic cirrhosis (0.40+/-0.09 units/ml) and of ten patients with disseminated intravascular coagulation (0.60+/-0.30 units/ml), but was normal in plasmas of patients with other congenital clotting factor deficiencies, nephrotic syndrome, rheumatoid arthritis, systemic lupus erythematosus, or sarcoidosis, or under treatment with warfarin. The plasmas of 21 mammalian species tested appeared to contain Fitzgerald factor activity, but those of two avian, two repitilian, and one amphibian species did not correct the coagulant defect in Fitzgerald trait plasmas. (+info)
Wasting of the small hand muscles in upper and mid-cervical cord lesions.
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Four patients are described with destructive rheumatoid arthritis of the cervical spine and neurogenic wasting of forearm and hand muscles. The pathological connection is not immediately obvious, but a relationship between these two observations is described here with clinical, radiological, electrophysiological and necropsy findings. Compression of the anterior spinal artery at upper and mid-cervical levels is demonstrated to be the likely cause of changes lower in the spinal cord. These are shown to be due to the resulting ischaemia of the anterior part of the lower cervical spinal cord, with degeneration of the neurones innervating the forearm and hand muscles. These findings favour external compression of the anterior spinal artery leading to ischaemia in a watershed area as the likeliest explanation for this otherwise inappropriate and bizarre phenomenon. (+info)
Overexpression of human homologs of the bacterial DnaJ chaperone in the synovial tissue of patients with rheumatoid arthritis.
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OBJECTIVE: To study the expression of the chaperone family of J proteins in the synovial tissue of patients with rheumatoid arthritis (RA) or osteoarthritis. METHODS: Rabbit antibodies specific for a synthetic peptide (pHSJ1: EAYEVLSDKHKREIYD), representing the most conserved part of all J domains thus far identified--among them the Drosophila tumor suppressor Tid56--were used in immunohistochemical analyses of frozen sections of synovial tissue and immunoblotting of protein extracts of adherent synovial cells. IgG specific for Tid56 was also used. RESULTS: Both antisera predominantly and intensely stained synovial lining cells from RA patients; other cells did not stain or stained only faintly. In immunoblots, anti-pHSJ1 specifically detected several bands with molecular weights of >74 kd (type I), 57-64 kd (type II), 41-48 kd (type III), and < or =36 kd (type IV). The strongest band detected in RA adherent synovial cells was the type II band, whereas in a B cell line, a type I band was prominent. CONCLUSION: Several potentially new members of the J family are described. The type II band represents the human homolog of the Drosophila Tid56 protein and is strongly expressed in RA synovial tissue. (+info)
Establishment and characterization of nurse cell-like stromal cell lines from synovial tissues of patients with rheumatoid arthritis.
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OBJECTIVE: To investigate the features of synovial stromal cells established from patients with rheumatoid arthritis (RA), and to define these cells as nurse cells. METHODS: Synovial nurse-like stromal cell lines (RA-SNCs) were established from patients with RA. These cell lines were examined for morphology, pseudoemperipolesis activity, cell surface markers, and cytokine production. The interaction between these RA-SNCs and a synovial tissue B cell clone was also examined. RESULTS: RA-SNCs had nurse cell activity. They spontaneously produced interleukin-6 (IL-6), IL-8, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor. Furthermore, they produced IL-1beta and tumor necrosis factor alpha and expressed higher levels of the other cytokines after coculture with the B cell clone. Proliferation and Ig production by the B cell clone were dependent on direct contact with RA-SNCs. CONCLUSION: These results indicate that the RA-SNCs were nurse cells. The findings suggest that RA-SNCs may play an important role in the pathogenesis of RA by producing large amounts of cytokines and maintaining infiltrating lymphocytes. (+info)
Economic consequences of the progression of rheumatoid arthritis in Sweden.
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OBJECTIVE: To develop a simulation model for analysis of the cost-effectiveness of treatments that affect the progression of rheumatoid arthritis (RA). METHODS: The Markov model was developed on the basis of a Swedish cohort of 116 patients with early RA who were followed up for 5 years. The majority of patients had American College of Rheumatology (ACR) functional class II disease, and Markov states indicating disease severity were defined based on Health Assessment Questionnaire (HAQ) scores. Costs were calculated from data on resource utilization and patients' work capacity. Utilities (preference weights for health states) were assessed using the EQ-5D (EuroQol) questionnaire. Hypothetical treatment interventions were simulated to illustrate the model. RESULTS: The cohort distribution among the 6 Markov states clearly showed the progression of the disease over 5 years of followup. Costs increased with increasing severity of the Markov states, and total costs over 5 years were higher for patients who were in more severe Markov states at diagnosis. Utilities correlated well with the Markov states, and the EQ-5D was able to discriminate between patients with different HAQ scores within ACR functional class II. CONCLUSION: The Markov model was able to assess disease progression and costs in RA. The model can therefore be a useful tool in calculating the cost-effectiveness of different interventions aimed at changing the progression of the disease. (+info)
Dose-loading with hydroxychloroquine improves the rate of response in early, active rheumatoid arthritis: a randomized, double-blind six-week trial with eighteen-week extension.
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OBJECTIVE: To investigate the usefulness of hydroxychloroquine (HCQ) dose-loading to increase the percentage of responders or rate of response in treating rheumatoid arthritis (RA). METHODS: Two hundred twelve patients with early RA (mean duration 1.5 years) were enrolled in a 24-week trial. Patients were stabilized with 1,000 mg naproxen/day and then began a 6-week, double-blind trial comparing treatment with HCQ at 400 mg/day (n = 71), 800 mg/day (n = 71), and 1,200 mg/day (n = 66), followed by 18 weeks of open-label HCQ treatment at 400 mg/day. RESULTS: All patients had mild, active disease at the time of initiation of HCQ treatment (31-43% rheumatoid factor positive; no previous disease-modifying antirheumatic drugs; mean swollen joint count 8.6-10.4). Based on the Paulus criteria, response during the 6-week double-blind portion of the study was 47.97%, 57.7%, and 63.6% in the 400 mg/day, 800 mg/day, and 1,200 mg/day groups, respectively (P = 0.052). Discontinuations for adverse events were dose related (3 in the 400 mg/day group, 5 in the 800 mg/day group, 6 in the 1,200 mg/day group). Most involved the gastrointestinal (GI) system, with the background naproxen treatment possibly contributing. Ocular abnormalities occurred in 17 of 212 patients (8%) but were not dose related. CONCLUSION: Dose-loading with HCQ increased the degree of response at 6 weeks in this group of patients with early, predominantly seronegative RA. Adverse GI events were dose related, while adverse ocular events were not. (+info)
Serum response elements activate and cAMP responsive elements inhibit expression of transcription factor Egr-1 in synovial fibroblasts of rheumatoid arthritis patients.
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Analyzing the induction kinetics and promoter elements regulating the expression of the transcription factor Egr-1, we found elevated levels of Egr-1-encoding mRNA in synovial fibroblasts of rheumatoid arthritis (RA) patients when compared to controls. By contrast, synovial lymphocytes and macrophages do not show an elevated Egr-1 transcription. Therefore, the overexpression of Egr-1 may serve as a diagnostic marker to characterize synovial fibroblasts of RA patients. To study the regulatory mechanisms controlling Egr-1 expression we analyzed the function of transcription factor binding sites located in the Egr-1 promoter. Individual transcription factor binding sites within the Egr-1 promoter were specifically mutated and Egr-1 promoter activity was tested using reporter gene constructs. Our experiments demonstrate that serum response elements are the main positive regulators and binding to a cAMP responsive element represents the major negative regulator for Egr-1 expression in synovial fibroblasts. In addition, we functionally defined a new element, which was not yet described in the human Egr-1 promoter and which serves as a second negative regulatory element for Egr-1 expression. Therefore increased serum response factor activity or failure of Egr-1 repressing signals may account for Egr-1 overexpression in RA synovial fibroblasts. (+info)
Survivorship and radiological analysis of the standard Souter-Strathclyde total elbow arthroplasty.
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We undertook a radiological analysis of 186 standard Souter implants to determine survivorship and to analyse the pattern of failure in those needing revision. The implants had been inserted as a primary procedure in patients with rheumatoid arthritis of the elbow at our hospital over the last 12 years. Taking revision as an endpoint, the survivorship after 12 years was 87%. If, however, revision and loosening, defined as the Hindex value equivalent to demarcation of 1 mm around the whole implant, are also included, the survivorship falls to 80%. Of the 24 implants revised, 18 (75%) were for problems with the humeral component, three (12.5%) with the ulnar component and three (12.5%) for instability. Loosening of the humeral component occurred when the implant extended into the humerus, with the tip moving anteriorly on to the anterior humeral cortex. Our study indicates that loosening can be predicted by the rate of change in this angle of extension of the prosthesis. (+info)