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ID PMID Title PublicationDate abstract
8587067 Fibronectin induces protease dependent focal matrix depletion and cell overlap in cultured 1995 May OBJECTIVE: To characterize the effect of added fibronectin (Fn) on human rheumatoid synoviocytes (RAS). METHODS: Early passage cultured RAS were studied by fluorescent imaging microscopy with multiple parameter overlaying and confocal laser scanning microscopy. RESULTS: Added Fn induced a localized decrease in matrix Fn at sites of cell overlap. Similar matrix depletion could be induced by collagen VI, cell binding (120 k) and heparin binding (60 k) fragments of Fn, but not by gelatin binding fragment (45 k). CONCLUSION: The decrease in matrix Fn was associated with the induction of a transformation-like phenotype of overlapping cell growth. Both phenomena were inhibited by serine protease inhibitors.
8368023 [Potential effects of nutrition including additives on healthy and arthrotic joints. I. Ba 1993 May Owing to the methodological difficulties involved, none of the studies so far published on the influence of diet on human osteo-arthritis has been fully comprehensive. We have therefore compiled a series of experimental observations--including some of our own--in the mouse and other species that have a bearing on this subject. Fats with a high content of saturated fatty acids, such as pork fat, greatly favored the development of spontaneous osteo-arthritis in the mouse, as also did cholesterol. Cottonseed oil and olive oil showed less tendency to do so. The highly unsaturated linoleic acid antagonized the effect of pork fat. Other vegetable oils and also fish oil exerted an anti-inflammatory and antinociceptive action in experimental animals. Foodstuffs rich in carbohydrates only promoted the development of degenerative joint disease in predisposed mice. Hyperglycemia (diabetes mellitus) constitutes a risk factor for the development of osteo-arthritis in humans as well as in mice and rats. A low-protein diet led to dysplasia of the hip joint in the dog; a high-protein diet inhibited the development of osteo-arthritis in the mouse, but promoted inflammation in volunteers. Disturbances of protein metabolism such as alkaptonuria can initiate degenerative processes in the joints of humans and animals.
7559691 Revision of failed total elbow arthroplasty. 1995 Sep We reviewed 25 patients with rheumatoid arthritis who had failure of 26 primary total elbow arthroplasties causing pain and loss of function. Most revision cases required special custom implants to treat varying bone loss and soft-tissue disruption. Assessment showed satisfactory functional results in the patients treated by revision at a mean follow-up period of 35 months. Our review suggests that revision surgery produces short- to medium-term painfree function, and is the treatment of choice for a failed total elbow arthroplasty in the absence of infection.
7754284 [Charcot, discoverer of diseases]. 1994 Aug Nowadays, one hundred years following Charcot's death (1893), neurologists remember his original contributions in the field of neurological disorders. The aim of this work is to assess the extraordinary Charcot's ability to create new diseases outside the field of neurology, mainly in internal medicine and in geriatric disorders. A good way to evaluate his abilities is to compare the state of medical knowledge before and after Charcot. Before, "chronic rheumatic disease" was not distinguished from gout and shaking falsy was confused with other tremors occurring in the elderly. Among vascular cerebral diseases ("apoplexy"), physicians could not recognize those following a bleeding process from those induced by an ischaemic brain disease. After Charcot's papers, these various disorders were better known and well defined from their pathology, aetiology and mechanisms. According to his obsessive personality, Charcot liked classifying and labeling diseases. Some nosographic frameworks were nevertheless inappropriate. Thus, in the field of joint disorders, Charcot included in the same pathological entity ("chronic rheumatic disease") various arthropathies such as rheumatic arthritis and osteo-arthritis. In France, this mistake hindered the understanding of the mechanism of these diseases. Though Charcot made mistakes when he described new pathological disorders, these mistakes were of little consequence, compared to the importance of his main nosologic contributions. As a whole, Charcot's scientific methodology seemed to be accurate and successful.
7794977 Reliability and validity of the CSSRD functional assessment survey in rheumatoid arthritis 1995 Mar OBJECTIVE: To demonstrate the reliability and validity characteristics of a fast, intensively focused functional assessment questionnaire that has been used in rheumatoid arthritis clinical trials by the Cooperative Systematic Studies of Rheumatic Diseases group (CSSRD). METHODS: Data from three double-blind, controlled clinical trials by CSSRD were used to examine the properties of the Functional Assessment Survey as a measure of physiologic function. RESULTS: The Functional Assessment Survey has reasonable test-retest reliability and convergent validity with the Steinbrocker et al. functional class. It demonstrated appropriate divergent validity with other clinical measures of response, as well as discriminant validity. CONCLUSIONS: The CSSRD Functional Assessment Survey is brief, intensive, and focused. Reliability and validity characteristics have been documented.
1538097 Sequential infection of silicone metacarpophalangeal joint arthroplasties resulting from s 1992 Jan We report a case of late multiple infected metacarpophalangeal silicone implants in a patient who had had replacement arthroplasty for treatment of rheumatoid arthritis. The patient had done well for 10 years after metacarpophalangeal joint arthroplasty when an implant infection developed. Over the next 4 years the remaining three implants on her dominant extremity also became infected necessitating their removal. The origin of the infections is thought to be the result of excessive and improper usage of the hand.
8838503 In vitro effects of 2 antirheumatic drugs on the synthesis and expression of proinflammato 1996 Jan OBJECTIVE: To compare the effects of tenidap, a new antirheumatic drug, with a nonsteroidal anti-inflammatory drug, naproxen, on the synthesis and expression of interleukin-1 beta (IL-1 beta), tumor necrosis factor (TNF-alpha), and interleukin-6 (IL-6) in rheumatoid synovium. METHODS: Human synovial membrane explants from patients with rheumatoid arthritis (RA) were incubated in the absence or presence of 20 micrograms/ml lipopolysaccharides (LPS) and tenidap at 50, 20 (therapeutic concentration), and 5 micrograms/ml or naproxen at 90 (therapeutic concentration) and 30 micrograms/ml. The levels of IL-1 beta, TNF-alpha, and IL-6 in the culture medium were measured by specific enzyme linked immunosorbent assays. The cytokine mRNA levels were quantitated by Northern blotting. RESULTS: In the absence of LPS, tenidap at 20 micrograms/ml produced a significant (p < 0.04) decrease in the IL-1 synthesis level. Under LPS stimulation, IL-1 beta synthesis was inhibited by tenidap at all concentrations tested (p < 0.01) and by naproxen at only 90 micrograms/ml (p < 0.01). Very small amounts of TNF-alpha could be detected only when the synovial membranes were stimulated with LPS. Tenidap significantly reduced LPS stimulated TNF-alpha synthesis; the maximum inhibition was noted at 20 micrograms/ml (69%, p < 0.002). Naproxen, at 90 micrograms/ml, reduced TNF-alpha synthesis by about 40% (p < 0.03) and values were similar to those with subtherapeutic concentrations (5 micrograms/ml) of tenidap. The spontaneous and LPS induced synthesis of IL-6 was significantly inhibited by tenidap at all concentrations tested, whereas neither concentration of naproxen demonstrated a significant effect. Tenidap induced a somewhat similar reduction pattern of IL-1 beta and IL-6 mRNA to that observed for cytokine synthesis. Naproxen only slightly reduced the LPS induced expression of IL-6, while enhancing the IL-1 beta expression. CONCLUSION: Tenidap and naproxen showed differences in their effects on cytokine synthesis and mRNA expression. Tenidap, at the therapeutic concentration, was most clearly differentiated from naproxen by its inhibition of IL-6, but was also a more potent modulator of IL-1 beta and TNF-alpha in RA synovial explants. The significance of these findings lies in the possible therapeutic benefit of proinflammatory cytokine suppression in joint disease.
8062318 Comparison of the efficacy, safety, and pharmacokinetic profiles of extended-release ketop 1994 Mar The efficacy and safety of two once-daily nonsteroidal anti-inflammatory drugs (NSAIDs) were compared in a single-center, double-blind, randomized, parallel-group study. Sixty patients with rheumatoid arthritis received either extended-release ketoprofen 200 mg or piroxicam 20 mg once daily for 3 weeks. Both treatments produced significant improvements from baseline in the primary efficacy variables (physician's global assessment, patient's global assessment, number of tender joints, number of swollen joints) at most visits. There were no statistically significant differences between treatments in any efficacy variable except the number of tender joints at week 3, favoring piroxicam. Both treatments improved the quality of sleep. Pharmacokinetic/pharmacodynamic evaluations were conducted on a subset of 29 patients, aged 57 to 71 years. No statistically significant differences in the pharmacokinetic parameters were noted between the first and last dose of extended-release ketoprofen; that is, there was no accumulation of ketoprofen. In contrast, a fourfold increase in peak concentration, a twofold increase in area under the concentration-time curve (AUC), and a 53% reduction in clearance were observed in piroxicam-treated patients. There was a direct relationship between AUC at steady state and three of four efficacy variables for ketoprofen. No correlation between the efficacy scores and trough plasma levels was seen with either drug. There were no significant differences between treatments in the number of adverse events. Elevated mean blood urea nitrogen levels and relative hyponatremia persisted 1 week after the end of treatment in piroxicam-treated patients. The results of this study indicate that extended-release ketoprofen and piroxicam are therapeutically comparable. However, extended-release ketoprofen, in contrast to piroxicam, reached steady state after the first dose, was rapidly cleared, and did not accumulate over the 3-week study period.
8162639 Polymorphisms in the TAP2 gene and their association with rheumatoid arthritis. 1994 Jan The human major histocompatibility complex (MHC) contains two closely related genes (TAP) that encode a family of transporter proteins. It is known that the TAP genes, like other MHC (class I and class II) genes, are polymorphic. In this study we investigated the polymorphisms in the ATP-binding domain of the TAP2 gene and examined the relationship of these polymorphisms to susceptibility to rheumatoid arthritis (RA). On the basis of the distribution of polymorphisms in these genes, three TAP2 alleles could be identified in homozygous typing cell lines, RA patients and normal subjects: TAP2*0101-1693.G, TAP2*0101-1693.A and TAP2*0201-1693.G. The prevalence of the variant (nucleotide A at position 1693), and thus also of the TAP2*0101-1693.A allele, was significantly (p < 0.006, RR = 4.25) higher in RA patients (35.3%) than in normal controls (11.4%). In addition, the TAP2*0101-1693.A allele showed significant (r = 0.45, p < 0.0003) association with HLA-DR4 only in RA patients and the prevalence of both TAP2*0101-1693.A and DR4 genes gave the highest relative risk (RR = 19.21, p < 0.0002) for RA. These data suggest that the MHC region containing both class II and TAP genes confers the strongest susceptibility to RA, with the highest RR value reported so far. It is likely that the genetic variability in the putative peptide transporter could also be implicated in immunological disorders associated with MHC.
1615680 [A main symptom of the climacteric manifestation complex: arthropathia climacteria]. 1992 In the last few years several studies have been published raising the question whether hormonal factors are co-responsible for the female prevalence of certain joint diseases. From our own clinical experience we know that more than half of the women seen at our outpatients department because of disorders of the post menopausal syndrome complain about arthralgies (especially of the PIP-joints). We have introduced the term "arthropathia climacterica" for it. Moreover the positive results of two clinical studies on which effects hormone replacement therapy had on these complaints indicate a relation between estrogens and joints.
7570206 [Clinical significance of IgG rheumatoid factor in patients with rheumatoid arthritis]. 1995 Jun We studied 135 patients with rheumatoid arthritis (RA) from February 1991 through June 1992 (mean period: 9 months) to measure serum IgG rheumatoid factor (IgG-RF) by the method of enzyme linked immunosorbent assay. In order to evaluate clinical significance of serum IgG-RF we compared the level of IgG-RF with some of the clinical and laboratory markers including disease activity index of RA and titers of IgM rheumatoid factor (IgM-RF) and IgA rheumatoid factor (IgA-RF). Positive IgG-RF (more than 2.0 on IgG-RF index) was observed only in 22.2% (30 patients) with the examination of the first collected serum samples but was increased to 41.5% (56 patients) by the case of total test samples. The number of patients with positive IgM-RF or positive IgA-RF test was significantly smaller in seronegative patient group than in seropositive patient group, whereas IgG-RF test showed no significant differences between these two groups. These indicate usefulness of consecutive test of IgG-RF for diagnosis of RA especially in seronegative patients. The mean of total score indicating radiographic bone destruction by Sharp's modified method was significantly higher in positive patients than in negative patients of IgG-RF. Multivariate analysis showed positive correlations between serum IgG-RF levels and erythrocyte sedimentation rates as well as between serum IgG-RF levels and Lansbury's indexes. These results suggest that the test of serum IgG-RF level is beneficial for daily management of patients with RA.
7990371 [Laboratory diagnosis of disseminated intravascular blood coagulation syndrome in patients 1994 DIC-syndrome frequently associated with anemia is one of rheumatoid arthritis complications which runs latently in the presence of hypercoagulation and low fibrinolytic activity. The development of DIC syndrome in the above patients correlates with the process activity, pattern of the disease, is independent of rheumatoid arthritis stage and duration, the patients' age, immunological and serological characteristics. Concentrations of circulating immune complexes and DIC-syndrome are related in rheumatoid arthritis patients with anemia.
8990933 [Cell adhesion molecules on lymphocytes and their role on signal transduction]. 1996 Dec It has been shown that cell adhesion molecules, which mediate lymphocyte adhesion have an ability to provide costimulation signals in the cells. One of the representative adhesion molecules on T lymphocytes, b1 integrin is comprised by several subunits sharing a common b1 subunits, CD29, which is defined by monoclonal anti-4B4 antibody. We have demonstrated that b1 integrins function as a cell surface receptor for extracellular matrix (ECM) protein, such as collagen and fibronectin. We also found that fibronectin, ligand of b1 integrin, synergized with anti-CD3 antibody to promote proliferation of CD4 T cell in a serum free culture system, and also induced an independent signal which would be distinct from the CD3/TcR-mediated signal pathway of activation through the induction of an AP-1 transcription factor. Recent studies revealed that there is an accumulation of CD4+CD29+ T cells, memory T cells as well as prominent increase of a variety of inflammatory cytokines in the synovial fluid of patients with rheumatoid arthritis (RA). This suggests that b1 integrins may play an important role for the inflammatory mechanism in RA. Regulation of signal transduction mediated by adhesion molecules on lymphocytes may be the possible effective way for controlling the pathological inflammatory process in RA.
1348198 Long-term second-line treatment: a prospective drug survival study. 1992 Apr The long-term use of second-line antirheumatic drugs was prospectively studied in a consecutive sample of 245 patients with recently diagnosed rheumatoid arthritis. A survival analysis was done in which treatment termination due to side-effects and to insufficient therapeutic effect were used as index causes. Cumulative drug 'survival' of aurothioglucose with treatment termination due to toxicity was significantly less compared with hydroxychloroquine. With regard to lack of efficacy as index cause, the administration time of hydroxychloroquine was significantly less than that of either aurothioglucose or sulphasalazine. Treatment termination due to lack of efficacy or combined insufficient therapeutic response and toxicity proved to be influenced by the initial disease activity and by the rank order of prescription.
7775811 Zyn-Linker delivery of antirheumatic agents. 1994 Despite our increasing ability to manage rheumatoid arthritis through systemic medication, refractory joints require local administration of more aggressive therapy in a substantial number of patients. These studies tested whether a new class of molecules designated Zyn-Linkers could deliver and retain therapeutics in a joint. Zyn-Linkers are synthetic lipid-like molecules designed to insert into cell membranes and enhance drug delivery to cells. After intra-articular injection into the knee of NZW rabbits, Zyn-Linkers bound rapidly and homogenously to synovial lining cells. Chelating Zyn-Linkers which contained Re-186 or Y-90 were synthesized to evaluate localization and retention after intra-articular injection. Initial studies using Re-186 Zyn-Linker gave excellent localization as evaluated by whole-body imaging: counts in the knee region represented > 90% of counts present in the whole body for at least 4-6 days postinjection. Similar results were obtained using a Y-90 Zyn-Linker and this agent was used for biodistribution studies due to its greater stability and ease of preparation. Efficacy and safety of Y-90 Zyn-Linker as a potential radiation synovectomy agent were estimated by extrapolation of biodistribution data to humans. A therapeutically effective dose of 8,000 cGy to synovium was calculated to require intra-articular injection of 3.4 mCi Y-90 Zyn-Linker, a value less than or equal to doses of particulate Y-90 agents used clinically in Europe. The predicted safety profile for Y-90 Zyn-Linker was excellent, with estimated doses to nontarget organs and tissues falling well within FDA-recommended safety levels for research-only radiopharmaceuticals. In addition to exhibiting desirable localization and retention properties, Zyn-Linkers may also be synthesized to release antirheumatic drugs such as methotrexate at controlled rates. This suggests substantial potential for these drug delivery molecules as chemical synovectomy agents which may be used concurrently with systemic chemotherapy to improve management of refractory joints.
7742156 Relative bioavailability of a new oral form of cyclosporin A in patients with rheumatoid a 1995 Feb The relative bioavailability of cyclosporin A (CsA) from a new microemulsion oral formulation (NEO) and the currently used soft gelatine capsule (SGC) was determined at steady state in 12 patients with rheumatoid arthritis. The AUC(0,12 h) values of cyclosporin A were significantly greater after NEO than SGC (2873 +/- 848 ng ml-1 h (mean +/- s.d.) vs 2355 +/- 1128 ng ml-1 h; P = 0.02, 95% CI (confidence interval of the difference: 81 to 955 ng ml-1 h). Cmax values were significantly higher after NEO than after SGC (811 +/- 244 ng ml-1 vs 495 +/- 291 ng ml-1, P < 0.0001, 95% CI of the difference: 209 to 422 ng ml-1).
7903012 [Basic therapy of rheumatoid arthritis. Comparison of methotrexate and sulfasalazine]. 1993 Oct In a retrospective analysis a total of 167 patients with rheumatoid arthritis (RA) who had been treated with the basic therapy formulas of methotrexate (MTX) or sulfasalazine (SUL) were evaluated with respect to therapeutical result and side effects after a period of 12 months. There was no randomization as to either MTX (n = 87) or SUL therapy (n = 80), but deliberate use of therapy according to prior treatment and activity of the illness. Apart from a significantly higher number of inflammatory joint conditions in the MTX group there was no difference in the two patient groups at the beginning of the study. MTX treatment led clearly to a more conspicuous activity decrease of the illness (ESR, joint index) and a more favourable effect on the locomotor function. Furthermore, the sphygmomanometer readings (for grip strength determination), the dose reduction of the concomitant prednisolone medication as well as the doctor's opinion were in favour of MTX. The portion of patients who had to discontinue the therapy because of side effects (= 11%) and lack of effect (= 9%) was exactly identical in both groups of patients. Both substances have shown to be effective basic therapy formulas for rheumatoid arthritis, while methotrexate has a few advantages.
8244441 Analysis of T cell receptor V beta regions expressed by rheumatoid synovial T lymphocytes. 1993 Aug The T cell receptor (TCR) V beta gene segment repertoire of T lymphocytes derived from peripheral blood of two healthy individuals and synovial tissue, synovial fluid and peripheral blood of three rheumatoid arthritis (RA) patients was analyzed. A sensitive assay based on the amplification of cDNA by the polymerase chain reaction (PCR) was used to analyze the levels of expression of 20 TCR V beta gene segment families. The relative expression of V beta gene segments in lymphocytes derived from peripheral blood, synovial tissue and synovial fluid was conserved over 155 days in one patient. V beta 9 transcripts were undetectable in the cells of this individual. In the two other patients the frequency of V beta 2 transcripts in synovial T cells of affected joints was significantly higher than in their peripheral blood lymphocytes. Dominance of distinct rearrangements among the V beta 2 transcripts from the synovial cells of these patients support the idea that the synovial T cell response is driven by antigen.
1467365 Effects of tumor necrosis factor alpha (TNF-alpha) on collagen arthritis. 1992 Oct Louvain rats were administered tumor necrosis factor alpha (TNF-alpha) via a continuous osmotic infusion pump. These rats were then immunized with native type II collagen (CII) to determine the effects of exogenous TNF-alpha on collagen-induced arthritis (CIA), an animal model of rheumatoid arthritis (RA). In this highly susceptible strain, 100% of experimental and control rats developed arthritis although TNF-alpha-treated rats had more severe disease as judged by both clinical and blinded radiographic parameters. Humoral responses to collagen were high in both groups, but cellular responses to CII were augmented by TNF-alpha. Serum IL-6 levels were significantly increased in all arthritic rats. This study suggests that TNF-alpha is a proinflammatory cytokine in CIA and that future studies targeting TNF-alpha might be therapeutic.
8929769 A study of serum androgen and cortisol levels in female patients with rheumatoid arthritis 1996 Jan Androgen status and the role played by androgens in the pathogenesis of rheumatoid arthritis (RA) in female patients are a matter of debate. In the present study serum testosterone (T), DHEAS, sex hormone binding globulin (SHBG) and cortisol levels were determined in 55 RA women, both in pre- and post-menopausal (M) status, and in a group of healthy subjects. Patients were divided into two groups according to disease activity and a correlation analysis of hormonal levels against serum IL1beta levels was performed. No significant differences were found in serum T levels between RA patients and controls, both in preM (1.38 +/- 0.4 vs 1.35 +/- 0.3 nmol/l; p = ns) and in postM status (1.21 +/- 0.2 vs 1.10 +/- 0.2 nmol/l; p = ns). Serum SHBG levels were lower in RA patients than in control subjects, both in pre and in postM status. DHEAS levels were significantly lower in preM RA patients than in controls (2.34 +/- 1.2 vs 5.93 +/- 1.6 mu mol/l; p < 0.001) while cortisol levels were significantly higher in preM active RA patients than in controls (466.2 +/- 30.3 vs 411 +/- 66.2 nmol/l; p = 0.02). IL1beta levels were significantly higher in RA patients than in controls both in pre- and postM subjects (70 +/- 33.8 vs 23.1 +/- 2.9 and 92 +/- 27.4 vs 31.9 +/- 3.1 fmol/l, p < 0.001, respectively). Although androgen status could play a role in the pathogenesis of RA, at present it is not possible to exclude the influence of RA itself on sex hormone profile.