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ID PMID Title PublicationDate abstract
1733350 Lipogranulomas and gold in the liver in rheumatoid arthritis. 1992 Feb Liver biopsies have been performed routinely as part of a protocol to evaluate methotrexate therapy in severe rheumatoid arthritis. All patients in the study had failed standard medical therapy, including gold treatment. Twenty-three of 41 patients (56%) had well-formed lipogranulomas (LGs) in the lobules, compared with an incidence of approximately 5% in our general biopsy population. Twenty-seven of 41 patients (66%) had a unique pigment in their livers. In 20 of these, the pigment was in LGs; in the seven patients with pigment not associated with lobular LG, it was found in lipid droplets in portal triads. The pigment varied from irregular pale brown granules slightly larger than those of hemosiderin, to smaller black round granules. Lipogranuloma-associated pigment of this type is an unusual finding, reminiscent of argyria. There was a variable appearance upon polarization, the black granules at times being strikingly refractile. There was a positive correlation between the prominence of LG and the quantity of pigment. The pigment resembled that described with gold deposition in other tissues. Radiographic microanalysis of both brown and black granules was performed in three cases. Characteristic spectra (energy-dispersive spectroscopy) demonstrated the presence of gold in each case. Silver was not identified. The high incidence of LG may reflect the frequent administration of gold in an oily vehicle. Gold may remain trapped in the liver for a prolonged time. Thus far, we have not detected any adverse effect from the presence of LG-associated gold.
8660395 Side-effects of drugs used in the treatment of rheumatoid arthritis. 1995 A number of anti-inflammatory and other drugs used in the treatment of rheumatoid arthritis have been screened for their ability to cause oxidative damage to lipids and proteins in vitro. Although many drugs exhibited an antioxidant profile, a few drugs tested were pro-oxidant, increasing peroxidation of arachidonic acid by mixtures of haem proteins and H2O2. This system may be an appropriate model to use in the inflammatory situation, since microbleeding to release haemoglobin occurs in the inflamed rheumatoid joint, where H2O2 is produced by invading neutrophils. The damaging effects of the pro-oxidant drugs phenylbutazone, meclofenamic acid and flufenamic acid were investigated in some detail using this system. Arachidonic acid peroxidation was accentuated in a dose-dependent manner and in the presence of haem proteins and H2O2, phenylbutazone also causes inactivation of alpha 1-antiproteinase, a major serine proteinase inhibitor in biological fluids. The above drugs may interact with ferryl haemoglobin, produced by the reaction of H2O2 with haemoglobin, to generate drug-derived radicals causing oxidative damage in these systems. If such reactions occur in vivo, they could contribute to the side-effects induced by these drugs on administration to certain rheumatoid arthritis patients.
1345061 [An association between ankylosing spondylitis and rheumatoid polyarthritis; comments on 3 1992 The article is an analysis of 3 clinical cases, characterized by the presence of the lumbosacral axial involvement, with the radiological evidence of a bilateral sacroiliitis and a peripheral polyarthritis displaying a rheumatoid picture, with rheumatoid factors in the serum and in 2 of the cases also in the articular fluid. These cases belong to the HLA-27 B histocompatibility type, a feature which could be, according also to the data of literature, an explanation of the association of these two diseases.
7751018 Sequence analysis of immunoglobulin heavy-chain variable region genes from the synovium of 1995 Mar To gain insight into the nature of B-lymphocyte responses in the synovium of rheumatoid arthritis (RA) patients, we amplified and sequenced immunoglobulin heavy-chain variable region genes expressed in seven IgM and three IgG-secreting synovial-derived hybridomas established from one patient. Each hybridoma V-region was encoded by unique VH-D-JH combination demonstrating that none of these hybridomas derived from clonally related B-lymphocytes in vivo. The expressed VH genes closely resembled (95.6%-100% homology) known germline VH genes in most hybridomas, including VH genes frequently used to encode autoantibodies. The antibodies produced by these hybridomas, with the exception of one IgM rheumatoid factor, did not bind to any of a large panel of autoantigens in enzyme-linked immunosorbent assay (ELISA), immunoblotting and immunofluoresence, suggesting that frequent expression of 'autoantibody-associated' VH genes does not correlate with detectable autoreactivity in this patient. Hybridoma CDR3 DNA was diverse in length and gene composition. Conserved heavy-chain cross-reactive idiotypes were expressed on 4/7 IgM- and 2/3 IgG-secreting hybridomas. The close similarity of expressed VH genes to germline counterparts of these hybridomas suggests that polyclonal activation is a prominent mechanism in B-lymphocyte activation in the synovium of this rheumatoid arthritis patient.
8137899 Effects of lipid peroxide on production of matrix metalloproteinase 1 (tissue collagenase) 1993 Dec The effects of linoleic acid hydroperoxide on the production of matrix metalloproteinases (MMPs) including MMP-1 (tissue collagenase), -2 ("type IV collagenase"), and -3 (stromelysin) and of tissue inhibitor of metalloproteinase 1 (TIMP-1), as well as DNA synthesis were investigated in rheumatoid synovial fibroblasts. Our results demonstrated that the levels of proMMP-1 and -3 and TIMP-1 were extremely elevated when 0.5-2.0 nmole/ml of linoleic acid hydroperoxide was added to cultures of rheumatoid synovial fibroblasts. DNA synthesis, however, was inhibited by linoleic acid hydroperoxide. These results indicate that lipid peroxide causes the disruption of extracellular matrix macromolecules and the inhibition of cell repair in synovial tissue. Therefore, they also suggest that an elevated level of oxygen free radical and/or lipid peroxides in synovial fluid may play an important role in the process of rheumatoid arthritis, resulting in the disruption of the joint.
1632662 Effect of fish oil on neutrophil chemiluminescence induced by different stimuli in patient 1992 Jul Lipid composition plays an important part in the structural and metabolic functions of cell membranes. In particular the production of inflammatory mediators such as prostaglandins and leukotrienes is dependent on polyunsaturated fatty acid precursors. Neutrophil leucocytes participate in inflammatory processes by their phagocytic and killing activities which can be monitored by measuring the photon emission (chemiluminescence). Chemiluminescence was measured in a luminol dependent system after stimulation by either particulate (zymosan) or soluble (phorbol myristate acetate) stimulus in a group of 10 patients with rheumatoid arthritis before and 21 and 45 days after treatment with a diet supplemented with eicosapentaenoic and docosahexaenoic acids. Ten patients with rheumatoid arthritis continuing their usual diet were used as control subjects. A progressive reduction of chemiluminescence stimulated by zymosan and phorbol myristate acetate was found in the patients treated with fish oil supplementation. This result correlated well with the reduction in erythrocyte sedimentation rate and an improvement of clinical parameters. The effects of fish oil derived lipids on neutrophil chemiluminescence are probably due to a change of the lipid composition of the cell membrane which is dependent on the esterification of eicosapentaenoic acid and docosahexaenoic acid in cellular membrane phospholipids. The modification of membrane lipid composition seems to interact in a non-specific way with the metabolic activation of neutrophils during phagocytosis.
7799384 Are there special considerations relevant to trials of biologic agents? 1994 Sep Although biologic agents have been developed to effect change in observed or hypothesized pathogenic pathways, discrepancies between biological and clinical effects are well recognized. In trials of these agents, biological and clinical effects need to be evaluated. While the biological effects require assessment to test the proposed primary effect and significant influences, clinical evaluation should use the same set of assessment procedures as pharmacological agents. The disease controlling antirheumatic therapy (DC-ART) classification with its requirement for longterm efficacy poses problems for the biological agents, which, in general, have demonstrated short term benefit. They may be best accommodated in a new "remission induction" category or, alternatively, as part of longterm combination therapy either with pharmaceuticals or with other biologicals to fulfill DC-ART requirements.
8672555 Natural ligand motifs of closely related HLA-DR4 molecules predict features of rheumatoid 1996 Jun 7 Rheumatoid arthritis (RA), one of the most common autoimmune disorders, is believed to be mediated via. T lymphocytes and genetic studies have shown that it is strongly associated with HLA-DR4. The DR4 subtypes DR4Dw4, DR4Dw14 and DR4Dw15 represent increased risk factors for RA, whereas DR4Dw10 is not associated with the disorder. Our study determines and compares the natural ligand motifs of these MHC class II molecules and identifies 60 natural ligands. At relative position 4 (P4), only the RA-associated DR4 molecules allow, or even prefer, negatively charged amino acids, but do not allow those which are positively charged (Arg, Lys). In the case of DR4Dw10 the preference for these amino acids is reversed. The results predict features of the putative RA-inducing peptide(s). A remarkable specificity, almost exclusively for negative charges (Asp, Glu), is found at P9 of the DR4Dw15 motif. This specificity can be ascribed to amino acid beta57 of the DR beta chain, and gives an important insight into the beta57-association of another autoimmune disease, insulin-dependent diabetes mellitus type I.
7473489 Catastrophic antiphospholipid syndrome with fatal acute course in rheumatoid arthritis. 1995 Aug A 34-year old woman, with a 3 yr history of severe seropositive rheumatoid arthritis (RA) with lupus anticoagulant and anticardiolipin antibodies, developed a massive anterior myocardial infarction and ischemia of the lower extremities, with disseminated intravascular coagulation resulting from extensive tissue damage. Seven days after admission, she died of severe heart failure complicated by ventricular fibrillation. To our knowledge, this is the first documented case of fatal acute antiphospholipid syndrome in RA.
7540009 Expression of E-selectin messenger RNA and protein in rheumatoid arthritis. 1995 Jun OBJECTIVE: To examine the de novo synthesis and cellular distribution of the E-selectin adhesion molecule in synovial tissues obtained from patients with rheumatoid arthritis (RA). METHODS: Immunohistochemistry techniques combined with in situ hybridization were used to examine RA synovium. RESULTS: There were numerous endothelial cells positive for E-selectin and E-selectin messenger RNA in the RA synovial membranes. Moreover, E-selectin expression appeared to correlate with inflammatory activity. CONCLUSION: The strong vascular expression of E-selectin indicates an activation of endothelial cells in the recruitment of cells associated with the chronic inflammation of RA.
8782130 Corticosteroid injection in rheumatoid arthritis does not increase rate of total joint art 1996 Jun OBJECTIVE: To determine the relationship between frequent intraarticular corticosteroid injection and subsequent joint replacement surgery. METHODS: A 1987 database of patients with rheumatic diseases was reviewed to find patients with rheumatoid arthritis (RA) who had received 4 or more intraarticular injections in an asymmetric pattern in a single year. RESULTS: A subset of 13 patients with an average of 7.4 years of followup was established as the cohort of a 5 year prospective study. In this highly selected cohort of patients with RA in a university practice who received 1622 injections, joint replacement surgery was not significantly more common in the heavily injected joints. CONCLUSIONS: A strategy of frequent intraarticular steroid injection does not greatly increase, through added risk of joint replacement, the risk inherent in continued disease activity for patients with established RA. Frequent corticosteroid injection may offer some chondroprotection when the alternative is continuous disease activity.
7553043 [A young woman with rheumatoid arthritis who rapidly developed secondary amyloidosis]. 1995 Feb A 22-year-old woman, who had been diagnosed as having rheumatoid arthritis (RA) 2 years before, was admitted to our hospital complaining of watery diarrhea (several times/day). She had been treated with low dose prednisolone (PSL) and auranofin in out-patient clinic. On admission, laboratory data showed moderate proteinuria (0.3 g/day) and positive CRP (2.7 mg/dl). Although the activity of RA was controlled by the administration of low dose methotrexate (7.5 mg/week) in addition to PSL, watery diarrhea and proteinuria did not improve. The biopsy of the stomach, rectum and kidney revealed the deposition of AA type amyloid protein, resulting in the diagnosis of secondary amyloidosis. Secondary amyloidosis has been reported as one of the common complications in RA patients, especially in old patients with a long history of RA. To our knowledge, however, there have been few reported cases who developed secondary amyloidosis so early during the course of RA as our case. We should be careful for the development of secondary amyloidosis even in young RA patients with short history of RA, when the disease is active.
8506693 [Radiology in degenerative diseases of the joints and spine]. 1993 A differentiation is made between primary and secondary forms of osteoporosis. Furthermore the degeneration forms of rheumatism are discussed.
8401816 Inhibition of the effects of rheumatoid synovial fluid cells on chondrogenesis and cartila 1993 Short-term co-cultivation of blastemal cells from 12-day-old mouse limb buds and human rheumatoid synovial fluid cells in high density cultures (Trowell culture system) resulted, depending on when co-cultivation started, either in (1) an inhibition of chondrogenesis (co-cultivation right from the start) or in (2) an extensive breakdown of cartilaginous matrix (co-cultivation after formation of embryonic cartilage). These synovial effects were markedly impeded if Avarol (a dioxygenase inhibitor) was applied singly or in combination with PAI-2 (a u-PA-inhibitor). PAI-2 alone, however, had no effect on the synovial-induced inhibition of chondrogenesis, but produced a pronounced inhibitory effect on matrix breakdown. The effects of both inhibitors were studied electron microscopically and biochemically (determination of sulfated-glycosaminoglycans in the high density cultures by Alcian Blue binding assay). The results of this study are consistent with the presumption that rheumatoid synovial cells are capable of inhibiting chondrogenesis and enhancing the breakdown of the cartilaginous matrix. Amongst others, the possible mediators involved are prostaglandins and plasminogen activators. The response to the inhibitors Avarol and PAI-2 is compatible with their mode of action. The chondroprotective action of these substances may be useful in developing potential antirheumatic drugs.
7620229 Patient predictors of caregiver burden, optimism, and pessimism in rheumatoid arthritis. 1995 Winter The authors of the present study investigated the relationship between rheumatoid arthritis (RA) patients' demographic, medical, and functional status and caregivers' burden, optimism, and pessimism. Subjects were 65 RA patients and their caregivers who were recruited from an outpatient rheumatology clinic. Each caregiver completed the Burden Interview to measure caregiver burden and the Life Orientation Test to measure optimism and pessimism. Each RA patient completed the Arthritis Impact Measurement Scale to measure pain and physical disability as well as a number of cognitive measures to assess two summary psychological cognitive factors labeled self-efficacy expectations and distorted cognitions. These cognitive factors were based on the following commonly used measures in RA research: the Cognitive Errors Questionnaire, the Arthritis Self-Efficacy Scale, the Coping Strategies Questionnaire, and the Pain Beliefs and Perceptions Inventory. Correlational analyses indicated that patients' functional and psychological measures (including poor self-efficacy expectations regarding symptoms) were related to caregiver burden, that patient self-efficacy expectations were related to caregiver optimism, and that patient physical disability was related to caregiver pessimism. Regression analyses revealed that, when competing with other demographic and disease severity variables, the relationships between patient self-efficacy expectations and caregiver burden and caregiver optimism, and patient physical function and caregiver pessimism remained significant. Taken together, these findings suggest that patient expectancies about control over arthritis-related symptoms (including pain) are strongly related to caregiver burden and caregiver optimism and that patient physical status is strongly related to caregiver pessimism.
7855679 The role of plate and screw fixation in occipitocervical fusion in rheumatoid arthritis. 1994 Nov 15 STUDY DESIGN: In a clinical retrospective study, the results of occipitocervical fusion in patients with rheumatoid arthritis were studied and analyzed. OBJECTIVES: The results of two different operative techniques were compared. The advantages of screw fixation compared with wiring techniques in this population of patients were investigated. SUMMARY OF BACKGROUND DATA: Numerous different implants have been presented in the literature for occipitocervical fusion in patients with rheumatoid arthritis. The use of wires being the standard fixation technique. METHODS: Occipitocervical fusion was performed in patients with rheumatoid arthritis: 26 patients with the wiring technique and 33 patients with a new Y-plate fixation. The results were compared at a follow-up period of 24 months and 50 months, respectively. Clinical and radiologic results were investigated. RESULTS: The atlantodental distance could be significantly better reduced in the group with the Y-plate fixation and the neurologic improvement in the wiring group was 40%, whereas in the Y-plate fixation 86% of neurologic improvement was observed. Pseudarthrosis was seen in 27% of the wiring technique and in 6% in the plate and screw fixation technique. CONCLUSIONS: In occipitocervical fusion for patients with rheumatoid arthritis, the screw and plate fixation technique provides superior results than other techniques using wire fixations.
1730102 T-cell receptors and rheumatic disease: approaches to repertoire analysis. 1992 Jan T-lymphocytes are thought to play a major role in the pathogenesis of a number of autoimmune rheumatic diseases. Techniques have recently been developed to study the T-cell receptor (TCR) usage of individual T-cells, and are likely to give major insight into the pathogenesis of rheumatic diseases. We describe the development of the TCR repertoire and the techniques available to study it. There is evidence that germline TCR complex polymorphisms may contribute to genetic susceptibility to rheumatoid arthritis. A number of studies have looked at rheumatoid synovial T-lymphocytes, some of which have found restricted TCR usage.
1439123 Immunotherapeutic approaches with monoclonal antibodies to immunological diseases. 1992 Sep The molecular events triggered by the interaction of the immune system with an antigen and leading to an immune response have been characterized in recent years. This information has provided the background to develop immunotherapeutic approaches to allograft rejection and to autoimmune diseases utilizing monoclonal antibodies to molecules which play a role in the immune response. The clinical trials performed thus far are described. The significance of the results obtained in these trials and the future potential developments are discussed.
8448639 Cyclosporin A in rheumatoid arthritis: overview of efficacy. 1993 Mar Five clinical trials of cyclosporin A (CyA) in the treatment of RA were reviewed and an initial evaluation made of clinical endpoints across the studies. A composite effect score for efficacy and the rates of dropout due to toxicity were each compared to earlier meta-analyses evaluating the relative efficacy and toxicity of second-line drugs for RA. The overall percentage improvements over a 6-month assessment period for the various clinical endpoints were all found to meet a minimal clinical improvement of 20%: tender joints, 20%; grip strength, 22%; swollen joints, 29%; functional index, 29%; morning stiffness, 40%; and CRP, 45%. The exception was ESR (16%). The composite effect for CyA indicated significant improvement over placebo (P < 0.001). This effect in excess of placebo was in the range of that found for antimalarial drugs. The toxicity associated with CyA was similar to that found with drugs with low toxicity, such as auranofin. A more detailed analysis using individual patient data and the results of two studies is planned.
8346710 Protein-losing enteropathy due to secondary amyloidosis of the gastrointestinal tract. 1993 Jun A case of a 71 year old woman who experienced weight loss, diarrhea and edema due to protein-losing enteropathy caused by amyloidosis secondary to rheumatoid arthritis is described. Amyloid deposits were found in the systemic organs, specifically in the bowel. The arterioles were massively involved within the laminae propriae and many were narrowed considerably due to amyloid deposits. Ulcerative lesions, which were accompanied with the ruptured arterioles, were also found. Lymphangiectasia was present in the submucosa, subserosa and mesenterium. The mesenteric lymphatic vessels were deposited markedly with amyloid. The principal cause of the protein loss might be related to the increased capillary permeability to plasma proteins and the exudation through an inflamed mucosa. Functional disruption of the lymphatic flow in the bowel and mesenterium might also participate in the mechanisms of the protein loss. Evidence in this study supports the theory that lymphatic disorders in some patients with gastrointestinal amyloidosis are one of the important factors in the pathogenesis of protein-losing enteropathy.