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ID PMID Title PublicationDate abstract
8043421 Anticardiolipin antibodies in rheumatoid arthritis: their relation to rheumatoid nodules a 1994 Jul One hundred and seventy-three consecutive patients with rheumatoid arthritis were examined for the presence of anticardiolipin antibodies (ACA), and for the clinical relevance and the relation of these antibodies to skin manifestations. Abnormally elevated IgG- and/or IgM-ACA levels were detected by an enzyme-linked immunosorbent assay in the sera of 55 (32%) patients. There was no statistical evidence of an association between ACA and a history of thrombosis in these patients. However, ACA were statistically significantly linked to the presence of rheumatoid nodules, which were found in 36 (21%) patients. In three patients, ACA were associated with vascular manifestations, including livedo reticularis, thrombophlebitis, and leucocytoclastic vasculitis. Our findings suggest that, although a subset of ACA may be linked to cutaneous vascular conditions, the major fraction of ACA in rheumatoid arthritis may have a different specificity than in other diseases, in which ACA are often linked to thrombotic events.
8624619 Increased expression of interferon (IFN)-gamma together with IFN-gamma receptor in the rhe 1996 Jan Data concerning the presence of T-cell-derived cytokines in the rheumatic joint are conflicting, challenging the hypothesis that rheumatoid arthritis (RA) is a T-cell-mediated disease. In this study synovial tissue specimens of 11 patients with RA and eight patients with osteoarthritis (OA) were stained for interferon-gamma (IFN-gamma) and its receptor. The level of expression of IFN-gamma was compared with that in tissue specimens of delayed-type hypersensitivity (DTH) reactions of the skin and of chronic tonsillitis. Furthermore, the percentage of T-lymphocytes which stained positive for IFN-gamma was determined using double staining techniques. IFN-gamma and its receptor were detected in all patients with RA and in 7/8 and 3/8, respectively, of patients with OA. Expression of IFN-gamma (P<0.02) and IFN-gamma receptor (P<0.01) in synovial tissue of patients with RA was more abundant compared with that in patients with OA. Although IFN-gamma could be detected in RA synovial tissue, the level of expression was less when compared with DTH reactions of the skin and tonsillitis. The percentage of CD3+ cells being positive for IFN-gamma was approximately 1% in RA, whereas in DTH reactions of the skin it was >90% and in tonsillitis approximately 30%. We conclude that the presence of IFN-gamma and its receptor in RA synovial tissue suggests a role for this cytokine in the ongoing immunological reaction of the inflamed joint.
8294759 Soft tissue reconstruction for rheumatoid swan-neck and boutonniere deformities: long-term 1993 Nov Ninety-two fingers with rheumatoid swan-neck deformity were treated with dorsal capsulotomy and lateral band mobilization. An initial increase of 55 degrees of motion into flexion was noted, but this proximal interphalangeal motion deteriorated over time. Of 15 fingers followed at 3 and 12 months, there was a mean loss of 17 degrees of the early postoperative flexion. Nineteen fingers with rheumatoid boutonniere deformity were treated with central slip reconstruction. The results were unpredictable, with only modest improvement in the proximal interphalangeal extension, which deteriorated over time. The authors now recommend arthrodesis for most severe rheumatoid boutonniere deformities.
8832982 Oral administration of an easily prepared solution of injectable methotrexate diluted in w 1996 Mar OBJECTIVE: To investigate whether the injectable formulation of methotrexate (MTX) given as an easily prepared oral solution of MTX diluted in water results in serum concentrations similar to those obtained with MTX tablets; to describe an easy and safe method of dispensing the drug. METHODS: Six patients (5 women, 1 man) with rheumatoid arthritis were given 10 mg of liquid MTX orally. The liquid was prepared by diluting 0.4 ml of the injectable formulation of MTX (50 mg/2 ml) in 8 ounces of water. One to 2 weeks later these patients were given 10 mg of MTX in the tablet form. MTX serum concentrations were determined using a fluorescence polarization immunoassay. The area under the concentration vs time curve (AUC), maximum concentration (Cmax) and the time to reach maximum concentration (tmax) were determined from the resulting concentration vs time curves. RESULTS: There was no statistical difference in the variables measured (AUC, Cmax, tmax), demonstrating comparable concentrations with these 2 methods of MTX administration. Patients found the medication easy to administer, potential hazards with the use of needles were avoided, and the cost of the drug was greatly decreased. CONCLUSION: The administrator of this easily prepared MTX solution is an alternative to the conventional administration of MTX tables, and may be of particular benefit in patients with financial limitations.
1729286 In vivo cyclooxygenase expression in synovial tissues of patients with rheumatoid arthriti 1992 Jan Cyclooxygenase (COX), or prostaglandin (PG) H synthase, plays a role in inflammatory diseases, but very limited data exist on the regulation of COX in vivo. We, therefore, studied the in vivo expression of COX in synovia from patients with rheumatoid arthritis (RA) and osteoarthritis (OA), as well as joints of rats with streptococcal cell wall (SCW) and adjuvant arthritis. Extensive and intense intracellular COX immunostaining, which correlated with the extent and intensity of mononuclear cell infiltration, was observed in cells throughout RA synovia. Significantly less or equivocal staining was noted in OA and normal human synovia. Similarly, COX immunostaining was equivocal in the joints of normal and arthritis-resistant F344/N rats. In contrast, high level expression developed rapidly in euthymic female Lewis (LEW/N) rats throughout the hindlimb joints and overlying tissues including skin, preceding or paralleling clinically apparent experimental arthritis. COX was expressed in the joints of athymic LEW.rnu/rnu rats 2-4 d after injection of SCW or adjuvant but was not sustained. Physiological doses of antiinflammatory glucocorticoids, but not progesterone, suppressed both arthritis and COX expression in LEW/N rats. These observations suggest that, in vivo, (a) COX expression is upregulated in inflammatory joint diseases, (b) the level of expression is genetically controlled and is a biochemical correlate of disease severity, (c) sustained high level up-regulation is T cell dependent, and (d) expression is down-regulated by antiinflammatory glucocorticoids.
7689005 Possible role of CD5+ B cells expressing CD23 in mediating the elevation of serum-soluble 1993 Since increased levels of serum soluble CD23/Fc epsilon RII (sCD23) were evidently demonstrated in patients with autoimmune diseases such as rheumatoid arthritis (RA), the possible mechanisms responsible for the elevation of serum sCD23 were investigated in RA patients. In keeping with increased serum sCD23, high proportion of CD23+ B cells was detected in the patients; this was associated with the enhanced expression of only Fc epsilon RIIa mRNA. Upon incubation at 37 degrees C, peripheral blood mononuclear cells of the patients spontaneously released high levels of sCD23 into the culture supernatant, while the CD23 expression on their B cells was considerably maintained even after the culture. Dot blot analysis further revealed that in contrast to normal subjects, RA patients showed no complete disappearance of Fc epsilon RIIa mRNA after the spontaneous culture. In addition, sCD23 release was significantly reduced in the patients by the addition of cycloheximide. It was also found that cycloheximide exerted the inhibitory influence on the spontaneous culture-mediated expression of CD23 on CD5+ but not CD5- B cells of the patients. However, the disappearance of CD23 from CD5+ as well as CD5- B cells of cord blood samples was unaffected by the agent. These results strongly suggest that CD5+ B cells of RA patients may be specifically activated by some mechanisms responsible for the persistent expression of Fc epsilon RIIa mRNA leading to the accelerated turnover of CD23 and in turn the increased release of sCD23.
7619674 Population pharmacodynamics of romazarit. 1995 Mar 1. The response to romazarit, a disease modifying anti-rheumatoid agent, was observed in patients with rheumatoid arthritis (RA) in a double-blind placebo controlled study. 2. Two hundred and twenty-four patients were recruited from 11 centres and treated with placebo or romazarit at a dose of 200 mg or 450 mg every 12 h for up to 24 weeks. Disease activity was measured using the Ritchie Index (RI). Plasma concentrations of romazarit were measured at each of up to eight assessments of RI. 3. The effect of romazarit was examined using analysis of variance (ANOVA) in 164 patients who contributed 61% of observations of disease activity. Observations after 12 weeks of treatment were excluded from ANOVA. 4. A population pharmacokinetic-dynamic model for the time course of disease progress and the response to placebo and romazarit was used to describe observations from all patients. 5. The population model suggested that the effect of romazarit was on the rate of progress of the disease and was describable by an Emax model. Concentration was a better predictor of response than dose. 6. Romazarit was significantly better than placebo in improving the RI in patients with RA. The placebo efficacy of romazarit treatment was similar to that associated with placebo treatment. 7. The population model provided a more complete description and explanation of the clinical pharmacology and therapeutic potential of romazarit than ANOVA.
8403545 Monocyte chemoattractant protein-1 (MCP-1) in inflammatory joint diseases and its involvem 1993 Oct Macrophages infiltrated into synovium play an important role in joint destruction in inflammatory joint diseases. In this study we focused on the production of monocyte chemoattractant protein-1 (MCP-1), a recently identified monocyte chemotactic protein, by inflammatory synovium. Synovial fluid (SF) from rheumatoid arthritis (RA), osteoarthritis, gout, and traumatic arthritis contained MCP-1. MCP-1 was produced in the synovium of patients with RA and other inflammatory joint disease in in vitro culture systems; differences in the amounts produced were not significant. Synovial MCP-1 production in RA was further investigated. Levels of MCP-1 were significantly correlated with levels of IL-1 beta, IL-6, and IL-8 in the culture supernatants of synovia from RA. Using immunohistochemical techniques, MCP-1 was detected in the lining and sublining cells and in the vascular endothelial cells of rheumatoid synovia. Rheumatoid synovia with active inflammation were stained more intensely by anti-MCP-1 antibody than were those with weak or inactive inflammation. IL-1 beta and TNF-alpha stimulated the expression of MCP-1 mRNA and de novo MCP-1 synthesis by cultured synovial cells. These results suggest the production of MCP-1 by synovium of various inflammatory joint diseases. In rheumatoid synovium, a cytokine network involving MCP-1 and other proinflammatory cytokines (IL-1 beta, IL-6, IL-8, and TNF-alpha) contributes to the immunopathogenesis of RA.
7660684 Immunological basis of oral tolerance. 1995 May Oral tolerance may be defined as a specific reduction in the immune response brought about by feeding an antigen. It has been reviewed by us recently as a possible treatment of rheumatoid arthritis. It has a respectably long history as an experimental phenomenon, in the course of which a variety of modes of action have been proposed. More recently the following mode of action has been proposed: An antigen, for instance foreign type II collagen, passes from the lumen of the gut across multifold-cells (M-cells) lying under Peyer's patches, and thence into antigen-presenting cells within the patches. These cells then activate a local population of T cells which specializes in the secretion of transforming growth factor-beta (TGF beta) and IL-4. Following activation a few of these cells wander out through the lymphatics and blood stream, and thence through tissue, until they again find type II collagen, their recall antigen. What they find in a patient with inflammatory arthritis, it is believed, is self-type II collagen exposed within the inflamed joints, which they recognize via its cross-reaction with the foreign collagen which had originally activated them. The specialized T cells are then stimulated by their recall antigen to secrete TGF beta and IL-4. These inhibitory cytokines suppress the activity of neighboring disease-inducing Th1 cells ("bystander suppression"). The latter cells presumably recognize one or more autoantigens, the nature of which is unknown. It need not be type II collagen, which figures in the whole story only as an organ-specific antigen, which lures the suppressive T cells to the right place.
8129776 Impaired glucocorticoid induction of mononuclear leukocyte lipocortin-1 in rheumatoid arth 1994 Feb OBJECTIVE: To investigate leukocyte lipocortin-1 production in rheumatoid arthritis (RA). METHODS: Eight control and 8 RA subjects received 100 mg hydrocortisone intravenously. Leukocyte lipocortin-1 was measured by enzyme-linked immunosorbent assay. RESULTS: Hydrocortisone induced significant increases in lipocortin-1 production by control mononuclear cells (MNC) (P = 0.006 versus baseline) but not by RA MNC (P = 0.44 versus baseline). Peak lipocortin-1 levels in control MNC were significantly higher than those in RA MNC (P = 0.014). CONCLUSION: These results indicate that glucocorticoid-induced MNC lipocortin-1 production is impaired in RA.
7763101 Evidence for differential effects of sulphasalazine on systemic and mucosal immunity in rh 1995 Apr OBJECTIVE: To study the effects of sulphasalazine (SASP) on the systemic and mucosal humoral immune systems in patients with rheumatoid arthritis (RA). METHODS: Serum concentrations of interleukin 6 (IL-6), class and subclass specific IgG, IgA and IgM, IgA and IgG antigliadin antibodies and rheumatoid factors (RF) of IgG, IgA (including IgA1 and IgA2 subclasses) and IgM isotypes were measured before and 16 weeks after sulphasalazine (SASP) therapy in 15 female and three male patients with RA. Amounts of immunoglobulins in saliva and jejunal fluid were measured as estimates of mucosal humoral immunity. RESULTS: Serum concentrations of IgA and IgG decreased significantly during SASP therapy and correlated with reduced concentrations of IL-6. In addition, levels of circulating IgA RF, IgA anti-gliadin antibodies and IgM RF decreased significantly after the treatment. In contrast, immunoglobulin levels in saliva and jejunal fluid were unaltered. CONCLUSION: SASP exerts powerful but selective inhibitory effects on systemic immunoglobulin production, whereas no effects on mucosal immunoglobulin production were observed. The decreased systemic B cell activity may be mediated by downregulation of the production of IL-6, a cytokine with Ig switching properties.
1472123 Rheumatoid synovium is enriched in CD45RBdim mature memory T cells that are potent helpers 1992 Dec OBJECTIVE: To delineate the phenotype and function of synovial T cells in rheumatoid arthritis (RA). METHODS: T cells from normal subjects or from RA peripheral blood (PB), synovial fluid (SF), or synovial tissue (ST) were analyzed phenotypically and functionally. RESULTS: RA SF and ST T cells were found to be markedly enriched in CD45RAdim, CD45RO+, CD45RBdim mature memory cells, whereas in the PB, CD45RAbright naive T cells were more frequent than CD45RO+ memory T cells, and only a minority were CD45RBdim. SF and ST T cells proliferated less well and produced less interleukin-2 in response to mitogenic stimuli than did PB T cells. However, synovial T cells effectively promoted the production of Ig from normal B cells. Moreover, PB and synovial T cells differed in their capacity to down-regulate immunoglobulin production. Anti-CD3-stimulated PB T cells suppressed Ig production unless their proliferation was prevented with mitomycin C. In contrast, synovial T cells were potent helpers of B cell Ig production regardless of antecedent treatment with mitomycin C. To examine the relationship between the CD45RBdim phenotype and B cell help, CD45RBdim T cells were sorted from PB. As opposed to the findings with synovial T cells, suppression by control PB CD45RBdim T cells was observed, but only when large numbers were employed. B cell Ig production was enhanced after treatment of PB CD45RBdim T cells with mitomycin C. In contrast, healthy control sorted CD45RBbright or sorted CD4+, CD45RO+, CD45RBbright T cells did not support Ig secretion. After treatment with mitomycin C, both of these populations were more effective helpers of Ig production. CONCLUSION: RA synovium is enriched in differentiated CD45RBdim memory T cells with potent helper activity and diminished capacity to down-regulate B cells, strongly implying an active role for these cells in the production of Ig in the synovium, and thus in the propagation of disease.
1317295 Stimulation of neutrophils by insoluble immunoglobulin aggregates from synovial fluid of p 1992 May Insoluble immunoglobulin aggregates present in the synovial fluid of patients with rheumatoid arthritis have been examined for their ability to activate reactive oxidant and granule enzyme secretion from bloodstream neutrophils. These insoluble complexes activated luminol chemiluminescence, but did not activate O2-, H2O2 or granule enzyme secretion and did not activate lucigenin chemiluminescence, which also measures reactive oxidant secretion. Hence, the luminol chemiluminescence detected after activation by insoluble immunoglobulin aggregates must be due to intracellularly generated reactive oxidants, i.e. produced within phagolysosomes. Because reactive oxidant and granule enzyme secretion has occurred within rheumatoid joints, other mechanisms of neutrophil activation must exist.
8337189 Measurement of functional ability and health status in the arthritic patient. 1993 May Chronic arthritis may have great impact on the patient but also on his or her family, relatives and friends. The assessment of the consequences of chronic arthritis and the effect of therapy not only in terms of physical, but also psychological and social dimensions deserves more attention. Functional ability and health status can be measured using a questionnaire or 'instrument', high-lighting important aspects not quantified with more traditional measurements. In this paper, arguments to apply such instruments more frequently are given. Health status instruments can be used not only to assess beneficial but also deleterious (side-) effects of therapeutic interventions. The properties are summarized of the most frequently used instruments assessing functional ability and health status. Many of these instruments have been evaluated sufficiently for validity and reliability; their sensitivity to detect change seems to be satisfactory. Therefore it is advisable to choose an internationally accepted, frequently used instrument, reflecting the area of interest.
7539824 Detection of T cells responsive to a vascular growth factor in rheumatoid arthritis. 1994 The primary lesion in rheumatoid arthritis (RA) is a destructive synovitis characterized by proliferation of endothelial cells, fibroblasts, and vascular smooth muscle cells, and with perivascular lymphocyte aggregates. A nonhematopoietic growth factor, acidic fibroblast growth factor (aFGF), may induce many of the biological features found in rheumatoid synovium, including T cell activation. To determine if aFGF-responsive T cells are increased in RA, we developed an assay to measure the frequency of peripheral blood T cells that are costimulated by aFGF. The data indicate that the frequency of aFGF-responsive T cells is increased in RA and may change with disease activity and treatment.
8714799 International consensus recommendations on cyclosporin use in rheumatoid arthritis. 1995 Guidelines for the use of cyclosporin in patients with rheumatoid arthritis have been formulated as a result of 2 International Consensus meetings. Clinical experience since the last meeting in June 1994 indicates that the clear and simple recommended guidelines remain valid. Experience in early identification of patients with a poor prognosis is growing, and trials currently underway will provide further evidence regarding the use of cyclosporin earlier in the course of severe disease. Confirmation of the potential benefits of the microemulsion-based formulation of cyclosporin (Neoral) relative to the conventional formulation (Sandimmun) will further strengthen the position of the drug in the management of patients with rheumatoid arthritis.
7914751 Interference of circulating azathioprine but not methotrexate or sulfasalazine with measur 1994 Apr Bioassays are currently used to measure the presence of functionally active cytokines in biological fluids. These assays may be influenced by the presence of other substances, either cytokine specific or not, in such fluids. In the present study, we analyzed whether some currently used disease-modifying antirheumatic drugs (DMARDs) could interfere with the measurements of circulating interleukin-6 (IL-6) bioactivity in the B9 hybridoma assay. When sera from healthy controls and patients treated with various DMARDs, such as azathioprine (AZA), methotrexate (MTX), intramuscular gold, and sulfasalazine (SASP), were tested in the IL-6 bioassay, an inhibitory effect was observed only with sera from patients treated with AZA. Addition of exogenous AZA, 6-mercaptopurine (6-MP), and MTX to the IL-6 bioassay resulted in a dose-dependent inhibition of the B9 cell proliferation induced by IL-6, AZA being most potent on a molar basis. Concentrations of AZA and 6-MP compatible with serum concentrations achieved in RA patients were able to inhibit the bioassay, but this was not the case for MTX. Exogenous SASP and its metabolites did not modify the IL-6-induced B9 cell proliferation. This study shows that circulating AZA (or its metabolites) exert an inhibitory effect in the IL-6 bioassay. This method is therefore not suitable to measure IL-6 concentrations in patients treated with AZA. Interference of drugs must be ruled out when bioassays are used to evaluate cytokine levels in biological fluids.
8966374 [Comparative study of the occurrence of gastrointestinal side-effects of tenoxicam and oth 1996 This research tries to determine the difference between granular tenoxicam (Tilcotil Roche) and other non-steroidal antiinflammatory drugs administered to patients with rheumatoid arthritis. The research comprised 143 patients with rheumatoid arthritis divided in two groups (71 + 72). As regards patients with rheumatoid arthritis, granular tenoxicam of a twenty-miligram dose daily showed both a good clinical effectiveness and a good bearing in long-term medicine taking, rarely causing gastrointestinal side effects, compared to other nonsteroidal antiinflammatory drugs in peroral taking.
8000737 Long-term follow-up of 46 patients with anti-(U1)snRNP antibodies. 1994 Dec The records of 46 patients with anti-(U1)snRNP antibodies and a minimal period of follow-up after first clinical presentation of at least 5 yr were examined with emphasis on symptoms contributing to established criteria of SLE, systemic sclerosis (SSc), RA or dermato- or polymyositis (DM/PM). At first clinical presentation 13 (28%) of the 46 patients studied fulfilled ARA-criteria for SLE (n = 10), RA (n = 2) and SSc (n = 1), and 33 (72%) were classified as mixed connective tissue disease (MCTD). During follow-up 18 patients initially classified as MCTD were now classified as SLE (n = 5), SSc (n = 7), RA (n = 3), or a combination of these disorders (n = 3). A transformation of MCTD towards these connective tissue diseases occurred 2.6 +/- 3 yr (mean +/- S.D.) after first clinical presentation. At the end of the follow-up period 67% of the patients fulfilled ARA criteria for SLE, SSc, RA or a combination of these diseases. The majority of patients with anti-(U1)snRNP antibodies have or will develop a classified connective tissue disease within 5 yr after clinical presentation. This undermines the concept of MCTD being a distinct clinical entity.
8614773 Chemiluminescence responses and chemotaxis of monocytes from patients with early rheumatoi 1996 We studied chemiluminescence (CL) responses and chemotaxis of monocytes of patients with early rheumatoid arthritis (RA) before starting anti-rheumatic drug treatment and correlated the data to 2-year prognosis of the patients. Luminol-enhanced CL responses of RA monocytes to N-formylmethionyl-leucyl-phenylalanine or to phorbol myristate acetate, and lucigenin-enhanced responses to opsonized zymosan particles were significantly higher than those of healthy control subjects. Distances of chemotactic, chemokinetic and random migration of RA monocytes were similar to those of control cells. High CL responsiveness correlated with seropositivity but not with presence of HLA-DR4 or that of erosions at 2-year follow-up. The results give credence to the view that monocytes are metabolically activated in early untreated RA, but increased respiratory burst activity does not predict early development of erosions.