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ID PMID Title PublicationDate abstract
7890786 Arthroplasty with a composite of an allograft and a prosthesis for knees with severe defic 1995 Mar We reviewed the clinical and radiographic results of fourteen patients who had a severe deficiency of bone and were managed with a massive allograft in conjunction with a standard total knee prosthesis between 1987 and 1990. The etiology of the bone loss included the failure of a previous total knee prosthesis, a supracondylar fracture of the femur or a fracture of the proximal part of the tibia, and débridement during the first stage of a reconstruction for the treatment of an infection. Thirteen patients had satisfactory clinical and radiographic results after the index procedure. The knee score of The Hospital for Special Surgery improved from an average of 24 points (range, 0 to 54 points) preoperatively to 82 points (range, 37 to 98 points) at the time of the most recent follow-up examination. The average duration of follow-up was forty-three months (range, twenty-nine to sixty-three months). The radiographic and functional results compare favorably with those that have been reported in most studies of otherwise comparable patients who had less deficiency of bone. While considerable risks are associated with the use of allograft bone and the true longevity of reconstructions with such bone is not yet known, the initial and short-term follow-up results support the use of allograft for the restoration of a functional knee joint in a patient who has a severe deficiency of bone.
8731215 Comparison and quantitation of wear debris of failed total hip and total knee arthroplasty 1996 Jun To compare the physical properties of debris particles associated with failed total hip and total knee arthroplasty, we applied a recently developed assay to electronically characterize the size, number, and composition of debris particles isolated from tissues adjacent to failed implants. We identified 21 samples (from 20 patients) of hip synovia and 35 samples (from 32 patients) of knee tissues that had been obtained at the time of revision arthroplasty. There were 12 females and 9 males in the hip group, and 16 females and 19 males in the knee group. Primary arthroplasty was performed for osteoarthritis (OA, 15 cases) or rheumatoid arthritis (RA, 6 cases) in the hip, and for OA (23) or RA (12) in the knee. Patients ranged in age from 23 to 85 (mean 59 years) for total hip, and from 27 to 84 (mean 61 years) for total knee arthroplasty. Implantation duration was from 5 to 123 months (mean 37.8) for total hip, and from 11 to 123 months (mean 63.1) for total knee arthroplasty. All of the implants were composed of cobalt-chromium alloy articulating with ultrahigh-molecular-weight polyethylene. The number of particles smaller than 10 microns ranged from 1.04 x 10(8)/g to 1.91 x 10(10)/g in the hip, and from 6.69 x 10(8)/g to 2.13 x 10(10)/g in the knee. Energy-dispersive X-ray spectroscopy and polarized light analysis showed both polyethylene and metal particles in most cases. The mean diameter of particles smaller than 10 microns was 0.72 +/- 0.2 microns in the hip, and 0.74 +/- 0.1 microns in the knee. Evaluation of particles larger than 10 microns showed a larger range of particle size in knee tissues (maximum 6.1 mm, mean 283 microns), than in the hip tissues (maximum 826 microns, mean 81 microns) (p < 0.001). Very small particles are common in both groups, but it appears that a larger range of particle sizes is present adjacent to failed knee than to failed hip prostheses. The higher frequency of large particles in failed knee prostheses probably reflects the perceived higher rate of delamination and fragmentation of tibial and patellar compared to that of acetabular polyethylene.
8356998 Efficacy and safety of nabumetone versus diclofenac, naproxen, ibuprofen, and piroxicam in 1993 Aug 9 In a randomized, open-label, controlled, multicenter, 12-week study, the efficacy and safety of nabumetone (1,000-2,000 mg/day) versus diclofenac (100-200 mg/day), naproxen (500-1,500 mg/day), ibuprofen (1,200-3,200 mg/day), or piroxicam (10-20 mg/day) were evaluated in patients with osteoarthritis (OA) or rheumatoid arthritis (RA). The results in elderly patients (> or = 65 years of age) are presented. Nabumetone was as effective as the comparator nonsteroidal antiinflammatory drugs (NSAIDs) in the treatment of elderly OA and RA patients. Ibuprofen and diclofenac caused significantly (p < 0.05) more abdominal pain than nabumetone (8.5%, 13.1%, and 4.1%, respectively). The frequency of abdominal pain was dose related for all NSAIDs except nabumetone. Diarrhea was reported by significantly (p < 0.02) more nabumetone-treated (6.6%) than ibuprofen-treated (0.9%) elderly patients, but the incidence of diarrhea was not dose related. There were no clinically significant changes in renal function with nabumetone or the comparator NSAIDs. A significant change in hepatic enzymes occurred in elderly patients treated with diclofenac (3.3%), which was different than for patients treated with nabumetone (p < 0.04), naproxen (p < 0.06), or ibuprofen (p < 0.06). With regard to withdrawals for adverse events, more (p < 0.04) piroxicam-treated patients (4.9%) withdrew than nabumetone-treated patients (1%). In addition, doubling the dose of nabumetone from 1,000 mg/day to 2,000 mg/day did not result in a proportional increase in adverse events. However, with the comparator NSAIDs, proportional increases in adverse events occurred with increased dose. Finally, the efficacy and safety of nabumetone in elderly patients were similar to the efficacy and safety observed in nonelderly patients.
1380541 Heteroclitic polyclonal and monoclonal anti-Gm(a) and anti-Gm(g) human rheumatoid factors 1992 Sep 1 Heteroclitic rheumatoid factors (RF) are specific for allotypic determinants, e.g., Gm(a) or Gm(g) on allogeneic, but not autologous IgG. All polyclonal RF we isolated from nine rheumatoid arthritis patients with circulating Gm(a-), (b+), (g-), (f+) IgG displayed dual heteroclitic activity for the Gm(a) and Gm(g) allotypes, as shown by using appropriate RBC agglutination assays and affinity columns bearing Gm(a+) or Gm(g+) IgG. To investigate possible mechanisms underlying the in vivo generation of heteroclitic RF, we tested the ability of nonspecifically and immune-specifically aggregated Gm(a-), (g-) IgG to function as targets for RF from Gm(a-), (g-) patients with rheumatoid arthritis. Heat aggregation (63 degrees C for 20 min) or binding to Ag (as in tetanus toxoid-antitetanus toxoid complexes) induced a "functional" Gm(a+) and/or (g+) phenotype in Gm(a-), (g-) IgG from five healthy subjects and five rheumatoid patients, as suggested by the ability of these altered IgG to function as efficient targets for six heteroclitic RF in direct binding and competitive inhibition experiments. That heterocliticity and dual Gm(a), Gm(g) specificity can be features of a single antibody molecule was formally demonstrated by analysis of a monoclonal RF (IgM mAb 61) generated from a Gm(a-), (g-) rheumatoid patient. RF mAb 61 displayed a high affinity (Kd, 10(-7) M) for IgG Fc fragment of Gm(a+) and (g+) IgG or aggregated autologous Gm(a-), (g-) IgG but did not bind to native autologous IgG. To investigate the molecular basis of the acquired Gm(a) phenotype, PBMC from five Gm(a-) patients with rheumatoid arthritis and two Gm(a-) normal subjects arthritis and two Gm(a-) normal subjects were cultured in vitro after activation with PWM. In most instances, these PBMC produced IgG that behaved as Gm(a+) in sensitive ELISA. Application of the polymerase chain reaction (PCR), using probes specific for the nucleotide sequence coding for the Gm(a) tetrapeptide, to the amplification of DNA from the in vitro-stimulated Gm(a-) normals or rheumatoid patients' PBMC provided no evidence for Gm(a) nucleotide sequences. The present data suggest that acquisition of the Gm(a) determinant by Gm(a-) IgG may result from subtle changes in the CH2-CH3 RF-binding region. Such changes would occur when Gm(a) IgG are complexed with Ag or nonspecifically altered, thereby providing a possible explanation for the induction of heteroclitic RF in Gm(a-) rheumatoid arthritis patients.
1343382 [Role of cytokines and growth factors in joint destruction processes]. 1992 Dec Cytokines and growth factors are important mediators of inflammatory reactions and play a central role in the physiologic regulation of bone and cartilage cell activities and in joint destruction. The net effects of cytokines on target tissues depend on the relative pericellular concentrations of several cytokines and their inhibitors in the inflammatory tissue. It is possible to suppress the effects of cytokines with natural or synthetic inhibitory molecules. The measurement of cytokines and their inhibitors may be useful to understand the pathogenesis and to develop new therapies for inflammatory joint diseases. In this review the following cytokines will be reviewed: interleukin 1 and its inhibitor, tumor necrosis factor alpha and its inhibitor, interleukin 6, interferon gamma, transforming growth factor beta, colony-stimulating factors, fibroblast growth factors, platelet derived growth factor and prostaglandins.
7690296 Tenascin is increased in cartilage and synovium from arthritic knees. 1993 Sep Tenascin is a major extracellular glycoprotein known to have important functions in processes such as wound repair and embryogenesis including bone and cartilage formation. The expression of this molecule in articular cartilage and synovium from normal and abnormal (OA and inflammatory joint disease including RA) human knee joints was studied by an immunohistological technique using paraffin embedded tissue and a specific anti-human tenascin monoclonal antibody (BC4). The results show that in normal articular cartilage tenascin is expressed in small amounts in the surface zone and in synovium is present in significant levels in the walls of blood vessels only. In diseased joints expression is greatly increased both in articular cartilage and synovium. Increased production of tenascin is likely to be part of a reparative response in injured joints the understanding of which may suggest novel mechanisms to modify disease progression in degenerative and inflammatory joint disease.
8988338 Interleukin-4 stimulates rheumatoid synovial fibroblasts to express matrix metalloproteina 1996 Dec In the present study, we investigated the effect of interleukin-4 (IL-4) on metalloproteinase 1 (MMP-1/tissue collagenase) production in human rheumatoid synovial fibroblasts. Northern blot analysis revealed that addition of IL-4 with or without histamine stimulated the cells to increase the amount of proMMP-1 mRNA, and the IL-4 with histamine addition resulted in a 3.3-fold increase compared with histamine only. Furthermore, IL-4 itself stimulated the expression of histamine H1 receptor mRNA. These results suggest that IL-4 may play an important role in joint destruction in RA.
8675223 Agalactosyl IgG and beta-1,4-galactosyltransferase gene expression in rheumatoid arthritis 1996 Apr Reduced galactosylation of immunoglobulin G (IgG) is well documented in rheumatoid arthritis (RA), but the reason for this defect is still unknown. There is some evidence supporting a defect in the biosynthetic pathway, and a reduction in the level of beta-1,4-galactosyltransferase (beta-1,4-GalTase) enzyme activity. Since glycosyltransferases are, in general, regulated at the level of transcription, we have measured the level of beta-1,4-GalTase gene expression in B cells from patients with RA and normal control individuals. We found no significant difference in mRNA levels for the transferase in these two groups (P > 0.7). MRL/Mp-lpr/lpr (MRL-lpr) mice develop a spontaneous arthritis with increased levels of agalactosyl IgG (G0). In spite of a significant reduction in the level of beta-1,4-GalTase mRNA in total spleen lymphocytes from MRL-lpr mice compared with the congenic MRL/Mp-(+/+) (MRL-(+/+) mice and with CBA/Ca mice, we found comparable levels of the beta-1,4-GalTase mRNA in purified B cells from both spleen and lymph nodes of the three strains. Amongst the lymphoid compartments examined, the spleen and peripheral blood were found to be the major contributors of G0 in MRL-lpr mice. These data indicate that in neither human RA, nor in an animal model of this disease, is reduced IgG galactosylation caused by impaired expression of the beta-1,4-GalTase gene in B lymphocytes. Furthermore, splenic B cells, which have normal levels of beta-1,4-GalTase mRNA, appear to be a major source of G0 in MRL-lpr mice.
7492224 Proinflammatory cytokine production and cartilage damage due to rheumatoid synovial T help 1995 Oct OBJECTIVES: To investigate the role of T helper-1 cell (Th1) activation in the induction of proinflammatory cytokine production and cartilage damage by rheumatoid arthritis (RA) synovial fluid mononuclear cells (SFMNC) and the subsequent possible beneficial role of the T helper-2 cell (Th2) cytokine interleukin-4 (IL-4) in the inhibition of this process. METHODS: SFMNC were stimulated with bacterial antigen (hsp60) to activate Th1 cells. Th1 and Th2 specific cytokine profiles (interferon gamma (IFN gamma) and IL-4) and proinflammatory cytokines interleukin-1 (IL-1) and tumour necrosis factor alpha (TNF alpha) in the conditioned media were analysed. In addition, the conditioned media were tested for their ability to induce cartilage damage. The same parameters were measured in the presence of IL-4. RESULTS: Stimulation of SFMNC with bacterial antigen resulted in an increase in IFN gamma, IL-1, and TNF alpha production which was accompanied by the induction of cartilage damage. Th1 activation could be inhibited by IL-4 as shown by a reduction of IFN gamma. This was accompanied by a decrease in IL-1 and TNF alpha production and inhibition of cartilage damage. CONCLUSIONS: Th1 activation is a possible mechanism by which inflammation in RA joints is enhanced. The Th2 cytokine IL-4 inhibits this Th1 activity and may diminish inflammation and induction of cartilage damage in RA joints.
8886214 Clinical efficacy and safety of Naprelan versus Naprosyn in the treatment of rheumatoid ar 1996 Sep A double-blind, randomized study compared the efficacy and safety of a controlled-release naproxen sodium formulation (Naprelan, Wyeth-Ayerst Laboratories, Philadelphia, Pennsylvania) 1,000 mg once daily; a conventional naproxen formulation (Naprosyn, Syntex Laboratories, Inc., Palo Alto, California) 500 mg BID; and placebo given for 12 weeks to 348 patients with rheumatoid arthritis (RA). This was followed by an open-label study to evaluate the safety of naprelan 1,000 mg once daily for an additional 9 months. In the double-blind phase of this study, the safety and efficacy of Naprelan 1,000 mg once daily were compared with those of Naprosyn 500 mg twice daily and placebo in 348 patients with RA. At the end of 12 weeks of treatment, Naprelan and Naprosyn were numerically superior to placebo in 3 of the 4 primary efficacy variables--physician's global assessment, patient's global assessment, and number of painful joints. Differences between Naprelan and placebo reached statistical significance for the patient's global assessment at Week 12 (Visit 7). Significantly more Naprosyn- than placebo-treated patients had at least 1 severe digestive system adverse event (AE); 1 drug-related AE; or 1 drug-related, digestive-system AE. There was no statistically significant difference in the number of AEs experienced by Naprelan-treated patients compared with those who received placebo. A total of 240 patients enrolled in the Naprelan open-label phase. As would be expected, patients initially treated with placebo showed significant improvement after starting Naprelan. Those initially receiving Naprelan or Naprosyn also maintained their improvement. The AE profile with Naprelan was similar to that reported in the double-blind phase. It was concluded that Naprelan 1,000 mg once daily was as effective as Naprosyn 500 mg BID in the treatment of RA and was particularly effective in relieving pain later in the day. The controlled-release formulation may also offer safety benefits.
1388638 Rheumatoid arthritis synovial fluid enhances T cell effector functions. 1992 Jun Rheumatoid arthritis is a chronic autoimmune joint disease of unknown etiology. T cells are believed to be important in the pathogenesis of rheumatoid arthritis since they infiltrate the joints and express several activation markers, such as MHC class II and IL-2R. In this study we have elucidated the effect on freshly isolated T cells of rheumatoid arthritis synovial fluid (RA-SF), which contains in vivo produced cytokines and enzymes. The mouse mixed lymphocyte culture (MLC) has been used as a model and specific cytotoxicity was evaluated against 51Cr-labelled sensitive target cells. Studies have shown that RA-SF contains a B cell differentiation activity that can cross-react between the human and murine species. Here we have shown that the addition of RA-SF strongly potentiates cytotoxic activity as well as lymphokine production by allogeneic activated effector T cells. The enhanced cytotoxicity induced by RA-SF was found to be due to a combined effect of increased cytotoxic T lymphocyte (CTL) precursor frequency, measured by limiting dilution analysis, and a more efficient killing on a per cell basis. Kinetic studies show that RA-SF must be added within 48 h after initiation of the MLC, otherwise the effect is lost. The target cell specificity of RA-SF was studied, using enriched CD4+ or CD8+ responder cells in the MLC. It was found that RA-SF could act directly on the CD8+ cells and potentiate their development to cytotoxic effector cells: this activity was not found when CD4+ responder cells were used instead. RA-SF could, on the other hand, greatly enhance IL-2 production by CD4+ responder cells. We suggest that B and T cell activity in RA-SF is important in the propagation of chronic inflammation in the joints of patients with rheumatoid arthritis.
7699637 Elevated plasma stromelysin levels in arthritis. 1994 Dec OBJECTIVE: To determine whether plasma concentrations of stromelysin-1 and gelatinase A are increased in patients with various forms of arthritis. METHODS: A sensitive and specific sandwich enzyme linked immunosorbent assay (ELISA), which employs a murine monoclonal antibody and a rabbit polyclonal antibody to human stromelysin-1, was used to measure plasma stromelysin-1 in 53 healthy subjects, 113 patients with various forms of arthritis and connective tissue diseases, and 65 patients with cancer. Gelatinase A was also measured in these patients using specific polyclonal and monoclonal antibodies to gelatinase A in an ELISA: RESULTS: The plasma concentration of stromelysin-1 (X +/- SEM) was significantly increased (p < 0.001) in patients with rheumatoid arthritis (RA) (187 +/- 14 ng/ml) and systemic lupus erythematosus (SLE) (258 +/- 35 ng/ml) as compared to both healthy control subjects (50 +/- 4 ng/ml) or patients with cancer (61 +/- 20 ng/ml). Plasma stromelysin-1 was also significantly increased in smaller groups of men with osteoarthritis (OA) and gout. In contrast, plasma concentrations of gelatinase A were not significantly increased in patients with RA, OA or gout. In healthy subjects, the concentration of stromelysin-1 was significantly higher in men than women. No correlation was noted between plasma stromelysin-1 levels and age. CONCLUSION: The detection of elevated plasma levels of stromelysin-1 in patients with RA is consistent with increased stromelysin-1 concentrations in inflamed synovial tissues in this disease. The origin of increased plasma stromelysin-1 in SLE is speculative. Measurement of plasma stromelysin-1 may be useful in the diagnosis and management of patients with various forms of arthritis.
8507220 Production of leukemia inhibitory factor by human articular chondrocytes and cartilage in 1993 Jun OBJECTIVE: To investigate the production of leukemia inhibitory factor (LIF) by human articular chondrocytes and cartilage. METHODS: Chondrocytes and cartilage were cultured with and without added cytokines, and the conditioned media assayed for LIF by a specific radioreceptor competition assay. RESULTS: Interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) stimulated LIF production by chondrocyte monolayers and cartilage. LIF was generally not detected in unstimulated cultures. Northern blot analysis showed increased amounts of LIF messenger RNA in IL-1- and TNF alpha-treated chondrocyte cultures. CONCLUSION: Chondrocytes, stimulated by IL-1 and/or TNF alpha, are potential contributors to the elevated levels of LIF observed in the synovial fluids of patients with rheumatoid arthritis and other inflammatory arthritides.
8095423 Lack of interaction between sulphasalazine and cimetidine in patients with rheumatoid arth 1993 Mar The interaction between sulphasalazine and cimetidine has been studied, a drug combination which is quite likely in view of the higher incidence of peptic ulceration in patients with RA. Nine patients with RA on sulphasalazine (group I) were given cimetidine 400 mg three times daily and followed up for 18 weeks. In addition, five patients on sulphasalazine alone (group II), who served as a control group, were also followed up in the same manner as group I. Monitoring included assessment of disease activity and haematological variables, and measurement of plasma and urinary levels of sulphapyridine and its metabolites. There was no significant change in either the haematological parameters or sulphapyridine pharmacokinetics upon administration of cimetidine. We therefore conclude that cimetidine may be safely used in patients with RA who are being treated with sulphasalazine.
8731243 Hypersensitivity to glucocorticoids: does it exist? 1996 Mar Hypersensitivity to corticosteroids is a classical but rarely reported event. We report a 30-year-old patient who developed generalized urticaria after her first methylprednisolone bolus. We reviewed the relevant literature to look for factors associated with hypersensitivity to corticosteroids. Causality should be evaluated on a case-by-case basis using diagnostic criteria for drug hypersensitivity reaction. Etiopathogenesis may involve either an IgE-mediated immunoallergic reaction or semi-delayed hypersensitivity. The main problems are identification of the offending agent and evaluation of the safety of further corticosteroid therapy. Although a few fatal reactions have been reported, some were probably due to underlying cardiovascular disease or serum electrolyte abnormalities.
8973616 The functional CD40 antigen of fibroblasts may contribute to the proliferation of rheumato 1996 Dec This paper demonstrates that CD40 is expressed on rheumatoid synovial pannus and primary fibroblast cell lines established from rheumatoid and osteoarthritic synovium as well as normal skin. Among various tested cytokines, interferon-gamma (IFN-gamma) and to a lower extent, tumour necrosis factor-alpha (TNF-alpha) were found to upregulate CD40 expression on fibroblasts. Synovial and skin fibroblasts cultured over CD40 Ligand transfected L cells (L-CD40 L) demonstrate a CD40 specific increase of DNA synthesis as measured by tritiated thymidine incorporation. Cell-cycle analysis and enumeration of viable cells further show that CD40 induced fibroblast proliferation. Costimulation with L-CD40 L and IFN-gamma resulted in maximal proliferation. Engagement of fibroblasts CD40 increased the IL-1-induced production of granulocyte macrophage-colony stimulating factor and macrophage inflammatory protein-1 alpha MIP-1 alpha. CD40 L activated fibroblasts showed decreased levels of CD40, but only marginal alterations of other cell-surface antigens. Taken together, the present results indicate that fibroblasts express functional CD40 and suggest a possible role of CD40 L expressing cells, such as activated T cells and mast cells, in the development of synovium hyperplasia.
7679410 Coexpression of phosphotyrosine-containing proteins, platelet-derived growth factor-B, and 1993 Feb Fibroblast growth factor (FGF)-1 and PDGF-B-like factors have been implicated in the pathobiology of RA and animal models of this disease. Since the receptors for FGF-1 and PDGF are tyrosine kinases, we examined the expression of tyrosine phosphorylated proteins (phosphotyrosine, P-Tyr) in synovial tissues from patients with RA and osteoarthritis (OA), and rats with streptococcal cell wall (SCW) and adjuvant arthritis (AA). Synovia from patients with RA and LEW/N rats with SCW and AA arthritis, in contrast to controls, stained intensely with anti-P-Tyr antibody. The staining colocalized with PDGF-B and FGF-1 staining. Comparative immunoblot analysis showed markedly enhanced expression of a 45-kD P-Tyr protein in the inflamed synovia. Treatment with physiological concentrations of dexamethasone suppressed both arthritis and P-Tyr expression in AA. P-Tyr was only transiently expressed in athymic nude Lewis rats and was not detected in relatively arthritis-resistant F344/N rats. These data suggest that (a) FGF-1 and PDGF-B-like factors are upregulated and may induce tyrosine phosphorylation of proteins in vivo in inflammatory joint diseases, (b) persistent high level P-Tyr expression is T lymphocyte dependent, correlates with disease severity, and is strain dependent in rats, (c) corticosteroids, in physiological concentrations, downregulate P-Tyr expression in these lesions.
1329774 Increased levels of soluble tumor necrosis factor receptors in the sera and synovial fluid 1992 Oct OBJECTIVE: Recently, 2 classes of cytokine inhibitors have been defined at the molecular level. The largest group comprises the extracellular domains of cell surface cytokine receptors, and includes both tumor necrosis factor receptors (TNF-R). The present study was conducted to investigate the role of TNF inhibitors in arthritis. METHODS: We measured p55 and p75 soluble TNF-R (sTNF-R) in serum and synovial fluid (SF) samples from patients with rheumatic diseases and compared their levels with levels of soluble interleukin-2 receptors (sIL-2R). Sensitive enzyme-linked immunosorbent assays (ELISA), specific for p55 and p75 sTNF-R and for sIL-2R, were used. RESULTS: Serum levels of p75 sTNF-R were 3-4-fold higher than levels of p55 sTNF-R, and both were significantly elevated in patients with osteoarthritis (OA) and rheumatoid arthritis (RA) compared with healthy controls. RA SF levels of sTNF-R were 4-5-fold higher than levels in serum, suggesting local production in the joint, and were significantly higher than levels in the SF of patients with seronegative arthropathy or OA. Furthermore, levels of p55 and p75 sTNF-R, but not sIL-2R or TNF alpha measured by ELISA, were increased in the SF of patients with clinically active RA. The soluble TNF-R in RA and OA SF were functional since they inhibited TNF activity in a cytotoxicity assay in proportion to the levels of inhibitor present. Evaluation of serially obtained serum samples suggested that sTNF-R may be a useful parameter for monitoring RA disease activity. CONCLUSION: Biologically active soluble TNF-R are up-regulated in patients with rheumatic disease and are produced locally in the joints. Measurement of serum levels of TNF-R may be useful for monitoring of disease, and determination of SF levels could be of diagnostic value.
7914739 Disease-modifying antirheumatic drugs, including methotrexate, sulfasalazine, gold, antima 1994 May Recently, there has been an interest in rethinking the classification of antirheumatic drugs. Emphasis continues to be on aggressive control of inflammation in the early phase of rheumatoid arthritis. The mistake of extrapolating short-term clinical trial results to long-term outcomes has been appreciated, pointing to the need for long-term studies. Interest in the role of cytokines and their receptors in the inflammatory process continues, as well as in the cellular mechanisms of action of the various disease-modifying antirheumatic drugs (DMARDs). Troublesome toxicity profiles continue to be reported, and a consideration of efficacy-toxicity trade-offs are important. Methotrexate still shows long-term efficacy, and low-dose folinic acid has been shown to reduce toxicity but not efficacy. New information on other DMARDs is presented, ie, sulfasalazine inhibition of signal transduction, the effects of hydroxychloroquine on cytokines and lipid metabolism, and the immunosuppressive effects of bucillamine, a penicillamine-related compound.
8886087 Metalloprotease activity, phospholipase A2 activity and cytokine concentration in osteoart 1993 Apr Collagenase, stromelysin and phospholipase A2 (PLA2) activity as well as interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha) and interleukin 6 (IL-6) concentration were determined in the knee joint synovial fluid (SF) of 26 patients with osteoarthritis (OA) and with rheumatoid arthritis (RA). Collagenase and stromelysin were detected in 80.7 and 69.2% of OA SF, respectively. When present, the mean activity of both enzymes was approximately two times lower in OA than in RA SF. PLA2 activity was present in all SF with no significant difference between OA and RA SF. IL-1 beta, TNF alpha and IL-6 were found in 0, 96.1 and 84.6% of OA SF, respectively. Mean TNF alpha and IL-6 concentration was also lower in OA than in RA SF. Metalloprotease activity correlated weakly with IL-6 level and enzymatic activities were unrelated with TNF alpha in OA SF.