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Tuberculous arthritis: A report of two cases with review of biopsy and synovial fluid findings.

Two cases of tuberculous arthritis with synovial fluid findings are presented, and the major series with culture results and synovial fluid analyses are reviewed. Synovial fluid cultures are positive for tuberculosis in almost 80 per cent of proved cases. Specimens obtained by open synovial biopsy are positive by histology or culture in over 90 per cent of proved cases. Little experience with closed needle biopsy has been published. About one-fifth of the patients with tuberculous arthritis will have a positive synovial fluid acid-fast smear for tubercle bacilli. The tuberculous synovial effusion invariably has an elevated protein level, fair to poor mucin clot formation and usually a low joint fluid sugar level. The synovial fluid white cell count is usually in the range of 10,000 to 20,000 cells/mm3, but it varies widely. Most fluids exhibited a predominance of polymorphonuclear leukocytes. The importance of bacteriologic or histologic study of the synovial fluid and membrane in establishing the diagnosis is emphasized. In general, this disease is different from tuberculous involvement of serous membranes both in the frequency of positive cultures and in the difference in cellular response.

Adult↗

13C NMR investigation of synovial fluids.

13C NMR spectra of synovial fluids from 20 patients suffering from rheumatic diseases have been recorded. Structural changes in hyaluronic acid, the main carrier of the viscoelastic properties of synovial fluid, could be observed in the NMR spectra of the native biological fluid. By comparing these spectra with those of purified hyaluronic acid, a rough estimation of the degree of depolymerization of synovial hyaluronic acid was possible. The patients with rheumatoid arthritis appeared to have a lower degree of polymerization compared to patients with osteoarthrosis. Thus, 13C NMR spectroscopy provides useful information about biophysical properties of synovial fluid.

Arthritis, Rheumatoid↗

Characterization of synovial fluid fibronectin from patients with rheumatic inflammatory diseases and healthy subjects.

Synovial fluid fibronectin from normal subjects and from patients who have rheumatic inflammatory diseases has been studied and compared with plasma fibronectin. The average fibronectin concentration in synovial fluids from normal subjects was 172 +/- 69 micrograms/ml; it was 721 +/- 315 and 556 +/- 349 micrograms/ml in synovial fluids from patients with rheumatoid arthritis and osteoarthritis, respectively. This is the first report on fibronectin concentrations in normal synovial fluids. Synovial fluid fibronectin from healthy subjects and patients with rheumatoid arthritis or osteoarthritis showed a molecular weight identical to that of plasma fibronectin. All normal and pathologic synovial fluid fibronectins showed a remarkably lower electrophoretic mobility compared with that of plasma fibronectin, when separated according to net molecular charge on agarose gel. Peptides from thermolysin digests of fibronectin from plasma and synovial fluid, when compared on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, showed distinct differences. These data demonstrate that synovial fluid fibronectin represents a molecular form which is structurally different from that of plasma fibronectin. This suggests that synovial fluid fibronectin is locally synthesized, possibly by a cell type which differs from that responsible for the production of the plasmatic fibronectin pool.

Aged↗

Interleukin-6 levels in synovial fluids of patients with rheumatoid arthritis correlated with the infiltration of inflammatory cells in synovial membrane.

To compare the histological appearance of synovial membrane and interleukin (IL)-6 levels in synovial fluids of patients with rheumatoid arthritis (RA). Synovial tissue and synovial fluids were obtained from 51 knee joints with RA undergoing synovectomy or joint replacements. A histological inflammation score was determined based on the hyperplasia of the synovial lining and infiltration of inflammatory cells. The concentrations of IL-6 in synovial fluids were measured by ELISA. The association between IL-6 levels and histological findings was evaluated. We found a positive correlation between the infiltration of inflammation cells in synovial tissues and the concentration of IL-6 in synovial fluids. The IL-6 level in synovial fluid partially reflects histological synovial inflammation.

Adult↗

Two-dimensional electrophoresis of synovial tissue, synovial fluid and serum in patients with rheumatoid arthritis and related diseases.

Using the technique of two-dimensional (2D) electrophoresis with consecutive silver staining, we investigated samples of serum, synovial fluid and synovial tissue obtained from 19 patients suffering from rheumatoid arthritis (RA) or non-RA arthritis. From these experiments we have drawn the following conclusions. 2D electrophoresis of serum, synovial fluid and synovial tissue extracts taken from patients suffering from joint diseases is a reproducible method. Repeated runs of the same sample reveal an essentially constant protein spot pattern. The time period between surgery and tissue preparation did not influence the number of protein spots when less than 15 h was involved. The protein spot number is always lower in synovial fluid than in either synovial tissue or serum in RA and non-RA patients. The mean value for the number of spots is 68 for the inflamed tissue irrespective of the cause of arthritis (RA and non-RA group taken together) and 47 for the control group. This difference is significant. We were able to definitely identify 7 spots in the tissue extract. We did not find RA-specific protein spots in either serum, synovial fluid or tissue extracts from the synovial membrane. The only significant difference between RA patients and either non-RA or control group patients concerning the protein spot pattern is the increased size of the immunoglobulin spot (mainly IgG) in RA. In addition, we discuss possible reasons for failure of the 2D electrophoresis technique to detect disease-specific protein patterns.

Adult↗

Differential production of RANTES and MCP-1 in synovial fluid from the inflamed human knee.

Synovial production of chemokines may play an important role in the recruitment of phagocytic leukocytes during inflammation. MCP-1, as well as RANTES mediate many different inflammatory diseases and are important in the recruitment of diverse leukocytes. We set out to study the different production of MCP-1 and RANTES in three different inflammatory conditions of the knee: arthrosynovitis, mechanical trauma, and hyperuricemia. In this study we evaluated if in each pathological condition mentioned above, there was a prevalence in production of one chemokine over the other. ELISA method was used to determine base production of the chemokines in the synovial fluid, serum and in supernatants from activated inflammatory cells. RANTES and MCP-1 messenger RNA (mRNA) was measured by semi-quantitative RT-PCR. Protein expression was detected by Western blot analysis. The synovial fluid cells from the knee of patients affected with arthrosynovitis, trauma, and hyperuricemia, expressed RANTES and MCP-1 and RANTES was produced in higher quantities than MCP-1 in all three pathological conditions. In patients treated with non-steroidal antiinflammatory drugs (NSAD) and dexamethasone, the levels of the two chemokines was reduced in serum and in synovial fluid. In addition, the synovial fluid cells from these patients released less RANTES and MCP-1 when compared to untreated patients. We conclude that in arthrosynovitis, trauma and hyperuricemia, RANTES and MCP-1 are both expressed and RANTES is produced in higher quantities. The fact that these chemokines are found in the three inflammatory diseases suggests that RANTES and MCP-1 are not specific to these inflammatory diseases, however they play a key role in inflammation by recruiting mononuclear leukocytes in the inflamed knee joint.

Anti-Inflammatory Agents, Non-Steroidal↗

Rheopexy of synovial fluid and protein aggregation.

Bovine synovial fluid and albumin solutions of similar concentration are rheopectic (stress increases with time in steady shear). This unusual flow characteristic is caused by protein aggregation, and the total stress is enhanced by entanglement of this tenuous protein network with the long-chain polysaccharide sodium hyaluronate under physiological conditions. Neutron scattering measurements on albumin solutions demonstrate protein aggregation and all measurements are consistent with a weak dipolar attraction energy (of order 3kT) that is most likely augmented by hydrophobic interactions and/or disulfide bond formation between proteins. Protein aggregation appears to play an important role in the mechanical properties of blood and synovial fluid. We also suggest a connection between the observed rheopexy and the remarkable lubrication properties of synovial fluid.

Animals↗

Synovial fluid lipids and apolipoproteins: a contemporary perspective.

Normal human synovial fluid contains extremely low concentrations of lipoproteins and apolipoproteins, in sharp contrast to those found in plasma. Increased amounts of cholesterol and other lipids have been found in the synovial fluid of a chronic inflammatory joint disorder, rheumatoid arthritis (RA). More recently, apolipoproteins AI, B and E have also been found in increased amounts in RA synovial fluid. Theories have been proposed to account for this increase in the amount of apolipoproteins and for the source of lipids and lipoproteins in normal synovial fluid; however, the mechanisms have not yet been established. Lipoproteins may play dual roles in synovial fluid: A functional one in normal synovial fluid and, as some suggest, a pathologic one in the abnormal synovial fluid of certain arthritic diseases. The recent data prompt the need to define synovial fluid lipids, lipoprotein particle subfractions and their constituent apolipoproteins, as well as their respective roles in synovial fluid.

Apolipoproteins↗

Evidence for enhanced interleukin 2 (IL-2) secretion and IL-2 receptor presentation by synovial fluid lymphocytes in rheumatoid arthritis.

Synovial fluid lymphocytes (SFL) and peripheral blood lymphocytes (PBL) from patients with rheumatoid arthritis (RA) and reactive oligoarthritis were investigated for activated T cells (Ia+SIg-), IL-2 receptor bearing cells (Tac+) and IL-2 production in vivo and in vitro. In contrast to negative results with blood, the synovial fluid of the arthritic joints contains considerable amounts of IL-2 activity (median: 11.8 mu/ml), elevated proportions of Ia+SIg- activated T cells (median: 12.5%) and of IL-2 receptor bearing cells (median: 2.5%). In vitro, after stimulation with several Concanavalin A (Con A) doses, SFL develop proportions of IL-2 receptor cells comparable to PBL. Furthermore, they produce higher values of IL-2 activity than comparable PBL cultures. The proportions of Ia+SIg- activated T cells increase only moderately after Con A stimulation compared to in vivo data, indicating different activated T cell subsets in the synovial fluid (Ia+SIg-, Tac+). The findings are discussed as an expression of an acute hyperactivation of lymphocytes in an inflamed joint.

Adolescent↗

Some humoral immunological aspects of the rheumatoid arthritis correlated with the ultrastructural changes of the rheumatoid synovial fluid.

We performed serologic and synovial investigations in rheumatoid (Latex 1/1280, 1/640, negative and Waaler Rose 1/1024, 1/512, negative), non-rheumatoid and control lots. The immunological results were correlated with ultrastructural changes found in the synovial fluid (SF) at the same titres of rheumatoid factor (RF). The pathologic values of the circulating immune complexes (CIC) (mean = 108.05 U), IgM (mean = 420 UI/ml), IgG (mean = 355.36 UI/ml), and anti-collagen II antibodies (mean = 558.6 U) were present at high titres of RF (Latex 1/1280, Waaler Rose 1/1024). These cases had also major ultrastructural changes of the nucleus and cytoplasm. We inferred from this the implication of the immune factors in the etiology and pathology of the Rheumatoid Arthritis (RA). The high, titres of RF were correlated with pathologic values of the C-reactive-protein (CRP) (mean = 13.31 mg%) and alpha-1-acid glycoprotein (A-1-GA) (mean = 158.3 mg%). The decline of the complement fraction C3 from the synovial fluid in RA confirms the immune character of the rheumatoid synovitis and may be useful in the diagnosis process. The significantly lower concentrations of the protease inhibitors alpha-1-anti-trypsin (A-1-AT) (mean = 165.1 mg%) and alpha-2-macroglobulin (A-2-M) (mean = 129.6 mg%) in synovial fluid suggest a diminution of the anti-proteasic activity due to local immune conflict.

Antigen-Antibody Complex↗

Serum and synovial fluid hydroxyproline fractions in microcrystalline arthritis and osteoarthritis.

Synovial fluid and serum hydroxyproline fractions were investigated in patients with osteoarthritis and microcrystalline arthritis. Synovial fluid dialysable hydroxyproline levels are higher than serum levels in both conditions. Synovial fluid total and dialysable hydroxyproline are higher in microcrystalline arthritis than in osteoarthritis, while non-dialysable hydroxyproline values are similar in both conditions. In microcrystalline arthritis, synovial fluid dialysable hydroxyproline and polymorphonuclear leukocyte counts closely parallel each other. Irrespective of the type of arthropathy, synovial fluid dialysable hydroxyproline levels correlate with urinary hydroxyproline excretion. While the data suggest overproduction of dialysable hydroxyproline by joints in both conditions, the overproduction appears to be mediated by polymorphonuclear leukocytes in microcrystalline arthritis only. The ratio of serum to synovial total hydroxyproline are further suggestive of a possible differentiation between osteoarthritis and microcrystalline arthritis. In the conditions governing the present study, urinary hydroxyproline may be used as an index of joint tissue collagen resorption. Finally the significance of synovial fluid and serum non-dialysable hydroxyproline is discussed.

Chondrocalcinosis↗

Synovial fluid cells in Reiter's syndrome.

Synovial fluid cells in Reiter's syndrome were studied by cell subset specific monoclonal antibodies and avidin-biotin-peroxidase complex staining. Mean leucocyte count was 9842/mm3 (9.842 X 10(9)/l), and 71% of all cells were polymorphonuclear leucocytes. 26 +/- 11 (SEM)% and 47 +/- 5% of all mononuclear cells in synovial fluid were M1+ monocytes and Ia+ cells, respectively. T11+ T lymphocyte was the predominant synovial fluid mononuclear cell (61 +/- 8%) but, in contrast to the inflammatory joint effusions in rheumatoid arthritis, T4+ cells clearly outnumbered T8+ cells in Reiter's syndrome. Thus the synovial fluid in Reiter's syndrome contains the immunocompetent and accessory cells required for immune response, which in fact is activated as suggested by lymphocyte Ia expression. Furthermore, in contrast with rheumatoid arthritis inducer/helper cells with T4 phenotype seem to be involved preferentially in the local pathogenetic mechanisms in Reiter's syndrome.

Adult↗

Effect of glycosaminoglycans on the detection of antibodies to collagen in synovial fluid.

Antibodies to collagen in the synovial fluid of RA patients were determined by radioimmuno assay using 14-C-labeled collagen and by passive hemagglutination with collagen coated erythrocytes. The effect of various glycosaminoglycans, possibly present in synovial fluid, on these two assays was investigated. None of the glycosaminoglycan preparations tested significantly changed either antibody titers or the amount of 14-C-radioactivity precipitated in radioimmunoassay. Digestion of the synovial fluid with chondroitinase ABC likewise had no effect on the results. It is therefore concluded that the glycosaminoglycans present in synovial fluid do not interact with native or denatured collagen under the experimental conditions existing in the determination of antibodies to collagen.

Antibodies↗

Soluble forms of P-selectin and intercellular adhesion molecule-3 in synovial fluids.

A number of adhesion molecules have been identified in synovial tissues of patients with rheumatoid arthritis (RA). Some of them are upregulated and may play an important role in the inflammatory processes of the diseased joint. In addition to synovial tissue cell surface expression, synovial fluids contain soluble forms of many adhesion molecules, such as intercellular adhesion molecule-1, E-selectin (sE-selectin), and L-selectin. In this study, we investigated the expression of soluble P-selectin (sP-selectin) and intercellular adhesion molecule-3 (sICAM-3) in synovial fluids from patients with RA, osteoarthritis (OA), and other forms of arthritis. sP-selectin and sICAM-3 levels in RA synovial fluids were significantly increased compared to those in OA. The levels of sP-selectin++ in synovial fluids correlated with sICAM-3 and sE-selectin in synovial fluids. The levels of sICAM-3 in synovial fluids correlated with synovial fluid leukocyte counts and erythrocyte sedimentation rate. In vitro, synovial fluid mononuclear cells produced sICAM-3 spontaneously. Elevated levels of sP-selectin and sICAM-3 in RA synovial fluids compared to OA may indicate inflammatory interactions between endothelial cells, leukocytes, and other synovial cells in the diseased joint.

Antigens, CD↗

Immunoblasts in synovial fluid and blood in the rheumatic diseases.

Synovial fluid studies have been made on 43 patients with rheumatic disease. Lymphocytes separated by a 2-stage procedure were examined for the presence of activated large lymphoid cells or immunoblasts. Such immunoblasts were found in 19 of 21 patients with classical rheumatoid arthritis and 7 of 10 patients with seronegative polyarthritis, including patients with Still's disease, psoriatic arthritis, and ankylosing spondylitis. No immunoblasts were seen in synovial fluid from osteoarthrosis or in the inflammatory but nonimmune synovial fluid from crystal-induced arthritis. The presence of immunoblasts showed a correlation with the lymphocyte count in the synovial fluid but not with the total white cell count. Preliminary studies confirm the spontaneous metabolic activity of these cells by autoradiography and show them by scanning electron microscopy to have a villous surface membrane. Simultaneous peripheral blood studies showed a lower incidence of immunoblasts than in the synovial fluid. It is suggested that these cells originate in the synovial membrane. In view of the known migration characteristic of immunoblasts these cells may be important in the spread of immune arthritis as well as being markers of disease activity.

Humans↗

Pathological human synovial fluids. Viscosity and boundary lubricating properties.

On human synovial fluids obtained during operations from the knee joints of 80 patients with different joing disease, relative viscosity was measured at 3 different shear rates and the boundary lubrication was tested by the coefficient of friction in an artificial rubber/glass system. The results were evaluated in relation to the operative findings. The viscosity showed statistically significant differences between the synovial fluids from the knee joints with rheumatoid arthritis, osteoarthritis, and torn menisci, being lowest in rheumatoid synovial fluid and highest in synovial fluids from knee joints with torn menisci. Correlations were found in the variations in the viscosity and the degree of synovitis. The boundary lubrication also showed different values inrelation to the different diseases. Synovial fluid from knee joints with torn menisci seemed to act as the best lubricant and significantly better than rheumatoid synovial fluid. Variations in the boundary lubrications reflect successive degrees of cartilage degeneration.

Arthritis, Rheumatoid↗

A novel method for the sampling of synovial fluid in mice. Assay of a synovial lysosomal enzyme in zymosan-induced arthritis.

A novel and very useful technique was developed to assay a lysosomal enzyme released into the joint synovial fluid during zymosan-induced arthritis in mice. This beta-glucuronidase activity correlated with histomorphological changes observed in the joint: vasculitis, synovitis and pannus formation. The antiarthritic drug triamcinolone acetonide improved both biochemical and histological parameters.

Animals↗