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ID PMID Title PublicationDate abstract
1626284 Fibronectin mediates anchorage-dependent focus formation in cultured human synoviocytes. 1992 Jun To determine the effect of extracellular matrix proteins on synoviocyte phenotype, a serum-free, defined-medium culture system was established. Rheumatoid synoviocytes maintained on type I collagen appeared monolayered, whereas cells maintained on fibronectin showed focus formation. Focus formation was abrogated by maintaining cells in the presence of antifibronectin. Focus formation was associated with a fibronectin-rich extracellular matrix, whereas monolayer morphology was associated with matrices containing a greater proportion of collagen. The abundant amount of fibronectin present in the synovial microenvironment may be partially responsible for the transformationlike phenotype displayed by rheumatoid synoviocytes.
8774162 Localisation of apoptosis and expression of apoptosis related proteins in the synovium of 1996 Jul OBJECTIVES: To investigate whether apoptosis occurs in the synovium of rheumatoid arthritis (RA), and the intermediate molecules operating in this process. METHODS: DNA fragmentation was detected by in situ nick end labelling (ISNEL) in the synovium of patients with RA (n = 11) and control patients with femoral neck fracture (n = 5). The expression of proteins p53, p21WAFI/CIPI, c-myc, proliferating cell nuclear antigen (PCNA), and Bcl-2 was also examined by immunohistochemistry. RESULTS: ISNEL positive synovial cells with apoptosis specific morphology were detected in extremely limited areas in only two RA synovial tissue specimens. Proteins p53, p21WAFI/CIPI, and c-myc, known inducers of apoptosis or cell cycle arrest or both, were expressed in the sublining cells independent of ISNEL positive cells. PCNA, a marker for cell proliferation, was observed in the synovial lining cells. Bcl-2, an inhibitor of apoptosis, was expressed mainly in infiltrated lymphocytes and in parts of the sublining layer cells of RA; it also did not correspond with ISNEL staining. CONCLUSIONS: Our findings indicate that RA synovial cells undergo apoptosis in addition to cell proliferation, but the frequency of apoptosis was very low. We suspect that the apoptotic process in the RA synovium may be suppressed by over-expression of Bcl-2. Although expressed proteins p53, p21WAFI/CIPI, and c-myc were present in the RA synovium, these protooncogenes are probably not implicated in the apoptotic process.
8164319 [The level of analgesia and changes in heart rate during spinal anesthesia]. 1994 Feb It is well known that high spinal anesthesia produces bradycardia. Studies are lacking, however, on the relation of changes in heart rate and the level of sympathetic blockade. Investigation was designed to elucidate the relationship between sympathetic blockade and heart rate during high spinal anesthesia. Subjects of the study were 70 rheumatoid arthritis patients who received spinal anesthesia with isobaric 0.5% bupivacaine. Cephalad spread of sympathetic blockade (loss of cold sensation to alcohol sponge) was determined at 30 minutes after injection of local anesthetics into the subarachnoid space. Heart rate was also measured before anesthesia and 30 minutes following spinal anesthesia. Heart rate was expressed by percent change. The results show that sympathetic blockade above T6 decreases heart rate more than 30%. In conclusion, sympathetic blockade above T6 by cold test produces 30% decrease in heart rate and this means that cardiac sympathetic denervation is almost complete at this level.
8542204 sIL-2R levels in rheumatoid arthritis: poor correlation with clinical activity is due in p 1995 Nov The serum levels of soluble interleukin-2 receptors (sIL-2R) were measured in an attempt to determine whether they correlated with 'disease activity' in 59 patients suffering from rheumatoid arthritis. Our results indicate that serum levels of sIL-2R do not permit patients to be classified as having active or inactive disease according to standard clinical indices. A correlation between sIL-2R and disease duration could offer one explanation for the current discrepancies found in the literature.
8697643 The relationship between exposed galactose and N-acetylglucosamine residues on IgG in rheu 1996 Jul The relationship between exposed galactose and N-acetylglucosamine on IgG in RA, JCA and SS was investigated. This was achieved using IgG isolated from serum where the levels of galactose and N-acetylglucosamine (GlcNAc) were detected using biotinylated lectins. Galactose and GlcNAc on IgG from patients with RA and JCA are inversely related, but in contrast, in SS, galactose expression on IgG decreased while GlcNAc expression remained similar to normal levels. Alterations in IgG glycosylation are closely associated with the development of adult and juvenile chronic arthritis and SS, but the changes involved are different in RA compared with SS, suggesting that the precise pattern of exposed sugars is associated with different rheumatological diseases.
1740536 The pharmacokinetics of flurbiprofen in younger and elderly patients with rheumatoid arthr 1992 Jan The pharmacokinetics of flurbiprofen (Ansaid Tablets, Upjohn Company of Canada, Don Mills, Ontario) were evaluated in both younger (40 to 60 years) and elderly (65 to 83 years) rheumatoid arthritic patients after both a 100-mg single-dose administration and at steady state during a 100-mg twice-a-day dosage regimen. Both flurbiprofen plasma concentration-time profiles and the urinary excretion of flurbiprofen and its major metabolites were evaluated. The results indicate that the pharmacokinetics of flurbiprofen are linear in both age groups based on only minor changes between single-dose and steady-state parameter determinations and the agreement between calculated and predicted accumulation values in plasma concentrations. Only minor differences in the pharmacokinetic parameters were observed between the younger and elderly patients. Only free flurbiprofen clearance was found to have a significant but variable correlation to patient age. The effect of flurbiprofen on the urinary excretion of two prostaglandins were also evaluated throughout this study. In both age groups, the maximum decrease in urinary excretion was observed after the first dose, and this effect was maintained throughout the remainder of the study. Percent decreases from baseline in urinary excretion during drug administration were similar for both age groups. Similar side-effect profiles were observed between age groups.
9015706 Articular cartilage destruction in experimental inflammatory arthritis: insulin-like growt 1996 Dec Rheumatoid arthritis, a disease of unknown aetiology, is characterized by joint inflammation and, in its later stages, cartilage destruction. Inflammatory mediators may exert not only suppression of matrix synthesis but also cartilage degradation, which eventually leads to severe cartilage depletion. Systemically and locally produced growth factors and hormones regulate cartilage metabolism. Alterations in levels of these factors or in their activity can influence the pathogenesis of articular cartilage destruction in arthritic joints. The main topic of the present review is the role of the anabolic factor insulin-like growth factor-1 in the regulation of chondrocyte metabolic functions in normal and in diseased cartilage. This is the most important growth factor that balances chondrocytes proteoglycan synthesis and catabolism to maintain a functional cartilage matrix. A brief overview of how chondrocytes keep the cartilage matrix intact, and how catabolic and anabolic factors are thought to be involved in pathological cartilage destruction precedes the review of the role of this growth factor in proteoglycan metabolism in cartilage.
8390712 Neutral endopeptidase (3.4.24.11) in plasma and synovial fluid of patients with rheumatoid 1993 In recent years the role of the peripheral nervous system has been focused on the pathogenesis of rheumatoid arthritis (RA). In particular, substance P (SP), released by the sensory terminals, has been demonstrated to be involved in cartilage breakdown [13]. The aim of our work was to study the levels of SP and its peptidases, neutral endopeptidase (3.4.24.11) (NEP) and angiotensin-converting enzyme (ACE), in the synovial fluid and plasma of 30 patients with RA and 14 patients with osteoarthritis (OA). ACE and NEP were determined with a fluorimetric assay and SP with a radioimmunoassay (RIA) method. ACE levels were normal in the plasma of patients with RA and OA (6.1 +/- 1.9 and 6.7 +/- 1.4 pmol/ml/min, respectively); we found no differences in the values, of ACE between RA and OA synovial fluid (5.7 +/- 4.2 and 5.5 +/- 4.1 pmol/ml/min, respectively). NEP levels were significantly increased in plasma (139.3 +/- 36 pmol/ml/min) and synovial fluid (133.8 +/- 32 pmol/ml/min) of patients with RA when compared to patients with OA (73.4 +/- 22 in plasma and 15.2 +/- 10.8 pmol/ml/min in synovial fluid) and healthy controls (89.7 +/- 14 pmol/ml/min in plasma). In synovial fluid, SP was significantly higher in RA patients (43.1 +/- 16.6 pg/ml) than in OA patients (12 +/- 13.1 pg/ml), while plasma levels did not show any difference (RA: 14.4 +/- 10.2; OA: 13.6 +/- 10.6; healthy subjects: 11.3 +/- 3.9 pg/ml). The only relationship detected in controls and in OA was among plasma NEP and ESR (P < 0.05) and synovial fluid NEP (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
8596138 Interleukin 10 cooperates with interleukin 4 to suppress inflammatory cytokine production 1995 Nov OBJECTIVE: Inflammatory cytokines have been implicated as important mediators of inflammation in rheumatoid arthritis (RA). We investigated whether interleukin 4 (IL-4) and interleukin 10 (IL-10) suppress the production of inflammatory cytokines by freshly prepared adherent rheumatoid synovial cells. METHODS: Adherent synovial cells were obtained from the rheumatoid synovium by collagenase digestion. The levels of IL-1 beta, tumor necrosis factor-alpha (TNF-alpha), IL-6, and IL-8 in culture supernatants were measured by ELISA. The gene expression of IL-6 and IL-8 were determined by Northern blot analysis. RESULTS: Freshly prepared rheumatoid synovial cells spontaneously produced large amounts of IL-6 and IL-8. However, the amounts of IL-1 beta and TNF-alpha produced were approximately 1000-fold less than those of IL-6 and IL-8. IL-4 alone inhibited the production of IL-1 beta, IL-6, and IL-8 by 32, 35, and 50%, respectively. IL-10 alone was less potent than IL-4 in suppressing these cytokines. Of note, the combination of IL-4 and IL-10 cooperatively exerted potent suppressive effects on the production of IL-1 beta, IL-6, and IL-8 by 74.3, 69, and 77%, respectively. The suppressive effects of the combination of IL-4 and IL-10 on IL-6 and IL-8 were also observed at the levels of mRNA. CONCLUSION: These results suggest that combination of IL-4 and IL-10 may be capable of suppressing the production of inflammatory cytokines at rheumatoid inflammatory joints.
8311557 Effects of hormone replacement therapy in rheumatoid arthritis: a double blind placebo-con 1994 Jan AIMS: To study the effects of ovarian hormone replacement therapy (HRT) on bone mineral density and disease activity in postmenopausal women with rheumatoid arthritis (RA). METHOD: A placebo controlled double-blind study was carried out on 62 patients with RA, 22 on placebo and 40 on HRT (transdermal oestradiol patches twice weekly for 48 weeks plus norithisterone tablets when clinically indicated). Bone mineral density of spine, hip and wrist was measured at 0 and 48 weeks and clinical and laboratory measures of general well-being and disease activity at 0, 12, 24 and 48 weeks. RESULTS: Thirteen of 22 (59%) of placebo and 31 of 40 (78%) of the HRT group completed 48 weeks in the study. At entry, bone mineral density (BMD) values in the lumbar spine and femoral neck were similar to those in age and sex matched controls in both treatment groups, whereas at the distal radius, BMD was significantly reduced to approximately 50% of control values (both p < 0.001 from controls). In the HRT group, spine BMD increased significantly by a median of +0.94% at 48 weeks (p = 0.024), but did not change significantly in the placebo group. BMD at the femoral neck and distal radius did not change in either group. In the HRT group, there was significant improvement in well being as assessed by the Nottingham Health Care Profile (p < 0.01) and in the articular index (p < 0.05). There were no significant changes in ESR or CRP in either group. CONCLUSION: Transdermal HRT was well tolerated, increased well being, reduced articular index and increased lumbar spine bone density over a one year period in postmenopausal women with RA. Although no laboratory evidence was found of a disease modifying effect, the symptomatic benefits and improvements in bone density indicate that HRT may be a valuable adjunct to conventional antirheumatic therapy in RA.
1411208 [Total prosthesis on a rheumatoid knee]. 1992 Jun Results of 81 total knee replacements in 67 patients with rheumatoid arthritis were studied. Mean follow-up was three years. Pain was the main reason for knee replacement surgery; knee mobility was well preserved prior to surgery. Failure occurred in four patients, as the result of infection, due in three instances to skin necrosis. Arthrodesis of the knee proved necessary in these patients. The fourth patient developed delayed hematogenous infection which was treated by a change of prosthesis. At follow-up, 82% of patients reported no pain and 18% moderate pain. Mean passive flexion was 113 degrees +/- 17 degrees. HSS score was 83.6 +/- 1.3 and all the patients except for the four with prosthesis failure stated that they were satisfied on very satisfied. Mechanical results were satisfactory, with a mean mechanical femur-tibial angle of 180.4 degrees. A circling line was visible at follow-up in 40% of operated knees but was partial in every case. No reoperations for prosthesis loosening were required. These data show that total knee replacement is the only reliable and radical treatment of rheumatoid arthritis of the knee and should be performed as soon as fixed flessum or axial deviation develops.
8136804 [Treatment of refractory rheumatoid polyarthritis by extracorporeal photochemotherapy]. 1993 Feb Extracorporeal photochemotherapy (EPC) has been used to treat cutaneous T-cell lymphomas as well as a number of immune-mediated disorders. Seven patients above 50 years of age with refractory rheumatoid arthritis (RA) were treated by EPC. Mononuclear cells were harvested, exposed to ultraviolet A light in the presence of 8-methoxypsoralen, then reinfused into the patient. This procedure was repeated eight times over a three-week period. Improvements in clinical parameters were seen in every case as early as the second week and persisted throughout the duration of EPC. Improvements for more than three months were observed in two patients. C-reactive protein levels declined during the treatment period. No adverse reactions were recorded. The mechanism of action of EPC in RA requires elucidation and a controlled study is needed to confirm the efficacy of this technique.
1605305 Stromelysin and tissue inhibitor of metalloproteinases gene expression in rheumatoid arthr 1992 Jun In situ hybridization was used to localize stromelysin mRNA in rheumatoid arthritis synovial tissue. Stromelysin antisense probes hybridized primarily to the intimal lining layer in frozen tissue sections, with little or no sublining signal. The expression of stromelysin correlated with cellularity as determined by hybridization with an actin probe. Double-label experiments were performed to detect tissue inhibitor of metalloproteinases (TIMP) and stromelysin mRNA simultaneously in synovial tissue. Coexpression of both mRNA species was identified in a subpopulation of intimal lining cells. In some highly inflammatory tissues, virtually all of the lining cells hybridized to both probes. However, in other tissues, expression of the two genes was discordant, with large numbers of TIMPpositive/stromelysin(negative) cells. Similar results were observed with late-passage cultured synoviocytes. Unstimulated cells did not express the stromelysin gene, whereas TIMP was constitutively produced. Addition of interleukin-1 beta (IL-1 beta) or tumor necrosis factor-alpha (TNF-alpha) to cultures induced the former but had little effect on the latter. Double-label experiments clearly showed discordant expression in individual cells. Stromelysin and TIMP genes likely have distinct transcriptional controls that provide precise control over the local environment and matrix turnover.
1489769 Randomized, controlled trial of compression gloves in rheumatoid arthritis. 1992 Dec A randomized, controlled trial was conducted to determine efficacy of the Isotoner and the Futuro compression gloves in 39 patients with hand synovitis secondary to rheumatoid arthritis. After 7 days of nighttime treatment, both brands of gloves were found to decrease subjective symptoms of pain and stiffness (p < 0.05). In addition, swelling of the proximal interphalangeal joints decreased, while range of motion, rate of finger motion, and grip strength all increased (p < 0.05). Compression gloves should be used with caution in patients with bilateral carpal tunnel syndrome, because 12 of 13 such patients experienced worsening of their symptoms following one nighttime wearing of compression gloves. While both gloves were found to be efficacious in improving the signs and symptoms of hand synovitis, neither glove was found to be superior to the other. Patient preferences related to glove composition and fit may ultimately determine which glove to prescribe.
8185694 Rheumatoid factor, HLA-DR4, and allelic variants of DRB1 in women with recent-onset rheuma 1994 May OBJECTIVE: To examine the relationship of rheumatoid factor (RF) to HLA-DR4 and alleles of DRB1 in women with recent-onset rheumatoid arthritis (RA). METHODS: Incident cases of RA were identified as part of a prospective, population-based case-control study. HLA typing was completed for 246 cases meeting criteria for definite or classic RA. RESULTS: One hundred thirty-six patients (55%) were positive for DR4, and 130 (53%) were RF positive. DR4 was found to be strongly associated with seropositivity (odds ratio 4.1, P < 0.0001). Patients with a shorter interval from RA onset to RF testing had a higher frequency of seropositivity than those with a longer interval (< or = 18 months 60%, > 18 months 33%). Further analysis of patients who had RF testing within 18 months of RA onset showed that the frequency of seropositivity was significantly greater among DR4-positive patients who had the shared sequence stretch of DR beta 1 associated with RA susceptibility (76% RF positive) than among DR1-positive patients who had this sequence (45% RF positive) (odds ratio 3.8, P = 0.01). Moreover, the frequency of seropositivity among DR1-positive patients with the sequence did not differ from that among all patients without the shared sequence (47%) (odds ratio 0.9, P = 0.8). CONCLUSION: HLA-DR4 is strongly associated with seropositivity in women with recent-onset RA. The amino acid sequence of DR beta 1 that is associated with susceptibility to RA and is shared between DR4 and DR1 appears not to be the primary determinant of seropositivity in these women.
8697654 Quantitation and distribution of vitronectin in synovial fluid and tissue of patients with 1996 Jan OBJECTIVE: Our study was undertaken to determine the quantity and pattern of distribution of vitronectin (Vn) in the synovial fluid and tissue of patients with rheumatic disease. METHODS: We quantitated synovial fluid Vn levels in 37 patients (17 with rheumatoid arthritis (RA), 12 with crystal induced arthritis (CIA), and 8 with osteoarthritis (OA)) using a competitive-binding ELISA: Immunofluorescence studies were performed on synovial pannus tissue specimens from 3 RA patients. SDS-PAGE analysis of the synovial fluids was performed to demonstrate the molecular forms of Vn present in inflammatory and noninflammatory synovial fluids. Albumin levels of synovial fluids were determined using an automated chemistry analyzer. RESULTS: Immunoreactive Vn was detected in 36 of 37 synovial fluid specimens examined, over a wide range of dilutions. Concentrations of Vn in inflammatory synovial fluid were significantly elevated compared to non-inflammatory synovial fluid and normal human plasma (NHP). Immunofluorescence studies revealed immunoreactive Vn most heavily concentrated in the lining layers of RA pannus tissue. Similar to NHP, molecular forms of Vn were heterogeneous in the synovial fluid; however, the inflammatory milieu appears to predispose Vn to cleavage at its protease-sensitive site. Overall there was a positive correlation of synovial fluid Vn to albumin. CIA and OA revealed a very strong relationship, whereas RA synovial fluid Vn levels correlated poorly to the levels of albumin. CONCLUSION: Vitronectin is present in synovial fluid. Levels are significantly enhanced in the inflamed joint and in the RA synovial lining, where it may influence cell adhesion and modulate tissue repair.
7582706 An audit of methotrexate and folic acid for rheumatoid arthritis. Experience from a teachi 1995 Oct We describe an audit of 158 patients with RA treated with weekly methotrexate and 5 mg of folic acid 24 h later. Our aim was to assess the safety and efficacy of this regime in our hands compared with published clinical trials of methotrexate in RA, and to examine patient outcomes. Treatment improved ESR, but only 69% of patients continuing therapy for prolonged periods believed their arthritis to be better on treatment. Health Assessment Questionnaire and Hospital Anxiety and Depression questionnaire scores in prospectively studied patients were not significantly altered by treatment. Toxicity occurred frequently (59% in those continuing and 89% in those ceasing therapy) and cessation of therapy solely due to lack of efficacy was rare. The probability of patients continuing with methotrexate and folic acid after 1, 2, 3 and 4 yr was 87, 76, 74 and 74%, respectively, figures that are at the upper end of the reported range for methotrexate alone.
7518830 Changes in cartilage metabolism in arthritis are reflected by altered serum and synovial f 1994 Jul The metabolism of the cartilage proteoglycan aggrecan was studied in patients with osteoarthritis (OA, n = 83), rheumatoid arthritis (RA, n = 127), and in controls (n = 117) using monoclonal antibody-based radioimmunoassays for glycosaminoglycans in the serum and synovial fluid (SF) to detect epitope 846 on chondroitin sulfate (probably only on recently synthesized molecules) and a keratan sulfate (KS) epitope AN9PI, present on intact and degraded molecules. Epitope 846 levels were always elevated in SF over serum (mean 38-fold in OA and 8.6-fold in RA) being highest in OA patients with the longest disease duration and greatest loss of cartilage, and lowest in RA joints with high leucocyte counts. Serum levels were more often elevated in RA (56%) than in OA (19%) and probably reflect increased aggrecan synthesis in diseased joints. KS levels were higher in SF than in serum in 69% of patients (up to 2.3-fold); levels were inversely (OA) and directly (RA) related to SF leucocyte counts. Serum KS was reduced in both diseases and in RA was inversely related to both systemic and joint inflammation markers. SF 846 levels were inversely related to SF KS in both diseases. These epitopes may provide a measure of the balance between cartilage synthesis and degradation in these diseases.
7939726 Early synovitis--synoviocytes and mononuclear cells. 1994 Jun Immunohistological observations of synovial tissues obtained at the onset of rheumatoid arthritis (RA) are limited and often reflect the diagnostic confusion inherent in any study of early synovitis. However, a critical analysis of published information and the authors' experience allow certain preliminary conclusions. Synovial lining cell hyperplasia and mononuclear cell infiltration are conspicuous in the earliest examples of synovitis. The changes in RA, however, are indistinguishable from those of other inflammatory joint disease. Conventional T-cell phenotyping does not distinguish early from late synovitis. Mature CD4+ lymphocytes are the predominant cells in both situations, but the presence of B lymphocytes or plasma cells may have diagnostic or prognostic value. The relationship of lining cell hyperplasia to subintimal cell infiltration is not defined; whether they develop simultaneously or one precedes the other remains an important unanswered question. However, it is clear that production of enzymes (metalloproteinases) believed to be important in extracellular matrix destruction is an early event.
8250988 Incidence of rheumatoid arthritis in central Massachusetts. 1993 Dec OBJECTIVE: To determine whether there is a secular decline in the incidence of rheumatoid arthritis (RA), as has been suggested by previous studies. METHODS: In the absence of comprehensive data in the United States population, we estimated RA incidence in a health maintenance organization population from 1987 through 1990 and compared the rates with those in an earlier, similarly performed study from Rochester, Minnesota, which covered the years 1950 through 1974. RA estimates were based on our review of medical records of patients who had been diagnosed as having RA or related diseases during the period of January 1, 1987 through December 31, 1990. RESULTS: Annual age-standardized incidence of classic or definite RA (according to the American College of Rheumatology [formerly, the American Rheumatism Association] 1958 criteria) in patients aged 18 or older was 22 per 100,000 in men and 60 per 100,000 in women. The incidence of RA increased with age, with a marked increase in women older than 50. CONCLUSION: We found no secular change in RA incidence compared with the similarly ascertained historical data.