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Demonstration of C1q - binding to collagen - anticollagen immune complexes in synovial fluids of RA-patients.

Collagen-anticollagen immune complexes were demonstrated indirectly in RA synovial fluids by digestion with collagenase and subsequent antibody determination. Elimination of C1q was performed by affinity chromatography using an anti-C1q column. Binding of C1q to collagen-anticollagen complexes was proven by demonstrating that collagenase-caused liberation of collagen antibodies was abolished or distinctly reduced after passage through the anti-C1q column. Binding of C1q to collagen-anticollagen immune complexes was proven via the fixation of these aggregates onto the anti-C1q column. This was achieved in those 7 RA synovial fluids which contained distinctly demonstrable collagen-anticollagen complexes.

Antibodies↗

The detection, quantification and partial characterisation of cathepsin B-like activity in human pathological synovial fluids.

In this study, the levels of the cysteine proteinase--cathepsin B were measured in diseased synovial fluids using a steady state fluorometric assay. Cathepsin B-like activity was shown to be present in all the samples analysed, with the rheumatoid arthritic synovial fluids possessing significantly higher concentrations (mean value ca. 416 mg/l) than the osteoarthritic fluids (mean value ca. 142.4 mg/l). In addition, upon treatment with pepsin, all of the rheumatoid arthritis samples were shown to possess additional cathepsin B-like activity, suggesting the presence of a reservoir of latent precursor molecules. By utilising a recently developed biotinylated affinity label for cathepsin B-like proteinases and sheep anti-(human cathepsin B) antibodies, used in combination with SDS-PAGE and Western blotting, the rheumatoid arthritic synovial cathepsin B was shown to exist in two forms with apparent molecular masses of M(r) 29,000 and 42,000. We propose that the former is a functionally active proteinase, whereas the latter is a pepsin activatable proform which, when cleaved by this aspartyl proteinase, is converted into a catalytically competent species of M(r) 20,000.

Affinity Labels↗

The determination of dehydroascorbic acid and ascorbic acid in the serum and synovial fluid of patients with rheumatoid arthritis (RA).

Using a novel high performance liquid chromatography (HPLC) determination of ascorbic acid and dehydroascorbic acid, we have measured the relative amounts of ascorbate and dehydroascorbate in 20 normal controls and in paired sera and synovial fluid from 13 patients with rheumatoid arthritis (RA). In complete contrast to previous published findings we were able to detect dehydroascorbate in normal human sera (12.0 +/- 3.7 mumol/l), while the mean and range of ascorbate measured in normals was 69.6 +/- 20.6 mumol/l. These findings were completely reversed in rheumatoid sera (21.8 +/- 8.6 mumol/l and 5.1 +/- 5.0 mumol/l for dehydroascorbate and ascorbic acid respectively). In several rheumatoid sera no ascorbate could be detected. In paired synovial fluid and serum samples, there was always more dehydroascorbate detected in synovial fluids than in the corresponding sera (p less than 0.01). The data suggests that the reduced level of ascorbate and increased level of dehydroascorbate may be a reflection of the increased antioxidant and free-radical scavenging activity of the vitamin in RA, especially within the inflamed joint.

Adult↗

White blood cell counts and differential in synovial fluid of aseptically failed total knee arthroplasty.

A cell count and differential was obtained on synovial fluid samples from 79 total knee arthroplasties undergoing revision for aseptic failure over a 5-year period. The mean white blood cell count (WBC) was 782/mL (range, 11-7,200/mL). The mean percentage of monocyte cells was 87%, and the mean polymorphonuclear leukocyte (PML) cell count was 13%. Eight patients (10.4%) had leukocyte cell counts >2,000. Five knees in 4 patients with rheumatoid arthritis had PML counts >50%. There was a single postoperative infection. In patients with osteoarthritis as a primary diagnosis, a synovial WBC of <2,000 and a differential with <50% PMLs had a 98% negative predictive value for the absence of infection. Key words: synovial fluid, cell count and differential, failed total knee arthroplasty, revision total knee arthroplasty.

Adult↗

Effects of Viscoseal, a synovial fluid substitute, on recovery after arthroscopic partial meniscectomy and joint lavage.

This was a pilot, single blind, randomised, controlled study in patients requiring partial meniscectomy. The aim was to assess whether replacing the synovial fluid lost during arthroscopy with a hyaluronic acid-containing synovial fluid substitute (Viscoseal) would reduce the severity and duration of post-operative symptoms during the 4 weeks post-surgery, in comparison to the standard arthroscopy procedure alone. Fifty patients were randomly assigned to either undergo arthroscopic partial meniscectomy alone (control group: n=25) or to receive 10 ml Viscoseal into the joint at the end of the procedure (Viscoseal group: n=25). Forty patients (20 per group) completed the study. Despite the small patient population in this pilot study, some interesting results were obtained. On Day 1 after surgery, the mean values for pain at rest (VAS) increased in both groups but this increase was lower in the Viscoseal group (8.9+/-23.1 mm) than in the standard therapy group (20.0+/-25.9 mm) (Mann-Whitney statistic MW-S: P=0.0525) and remained in favour of Viscoseal for the first 3 days after surgery. Joint swelling decreased to a greater extent in the Viscoseal group with an observed superiority at Day 7 (MW-S: P=0.1187) and a proven superiority at Days 12 (MW-S: P=0.015) and 28 (MW-S: P=0.0072). Diclofenac intake was lower in the Viscoseal group from Day 3 to Day 28 with a proven superiority (LB-CI > 0.5) in favour of Viscoseal on Days 3 (MW-S: P = 0.0093), 4 (MW-S: P= 0.0075), and 7 (MW-S: P = 0.0195) indicating that the product had an NSAID-sparing effect. Viscoseal was safe and well-tolerated and no adverse reactions occurred during the study. These findings indicate that Viscoseal may be useful as a synovial fluid substitute after arthroscopy.

Activities of Daily Living↗

High levels of interferon in synovial fluid of retrovirus-infected goats.

A high level of interferon (IFN) was found in the synovial fluid of goats with naturally acquired caprine arthritis-encephalitis (CAE), a disease caused by caprine arthritis-encephalitis virus (CAEV), a nononcogenic retrovirus of the lentivirus group. Intraarticular injection of CAEV or control inoculum in the joints of affected goats caused increased amounts of IFN production in synovial fluid.

Animals↗

The metabolism of synthetic leukotriene B4 in synovial fluid and whole human blood.

The metabolism in vitro of synthetic leukotriene B4 (LTB4) in synovial fluid from rheumatoid arthritis and osteoarthritis patients and in whole blood from these same patient groups and from normal volunteers has been studied. A linear relationship existed between a plot of the time of incubation of samples with LTB4 and the percentage of the initial concentration of LTB4 at each time point. The slope of this line, the rate constant for metabolism, has been used to compare different samples. LTB4 was metabolised more rapidly in the synovial fluid of rheumatoid arthritis patients than osteoarthritis patients. Furthermore, LTB4 was metabolised more rapidly in the blood of rheumatoid arthritis patients than either osteoarthritis patients or normal volunteers. These differences in metabolism correlate with the polymorphonuclear leukocyte (PMN) and albumin content of samples. It is suggested that binding of LTB4 to albumin in vivo will in part determine the available concentration of LTB4 in inflammatory lesions.

Arthritis, Rheumatoid↗

Serum and synovial fluid osteocalcin (bone gla protein) levels in joint disease.

Osteocalcin (bone gla protein) is a sensitive marker of bone turnover in metabolic disease. Using a well characterized antiserum (R 102M) we have assayed serum and synovial fluid samples from patients with osteoarthritis (OA) and rheumatoid arthritis (RA) and related levels to serological and radiological markers of disease. There were 21 patients with RA (mean age 58.2 years, 15 F) and 33 with OA (mean age 69.2, 28 F). Paired serum and synovial fluids (SF) were available in 19 RA patients and 30 OA patients. Serum osteocalcin levels were related to age-/sex-matched normals and to a small group of elderly disease controls. Serum levels tended to be lower in RA than controls, but not significantly so: RA 5.56 (3.67); control 6.09 (2.54) ng/ml; expressed as mean (SD) and the mean serum/SF ratio was 0.88 (0.86). The results were much more variable in OA (mean serum osteocalcin 6.1 (3.9]. Elevated levels were mainly due to a small number of patients with a destructive form of OA and were higher than those with non-destructive OA (10.3 (3.5), n = 20, versus 3.83 (1.6), n = 10). Patients with non-destructive OA had a lower serum osteocalcin than age-/sex-matched normals. In this study, synovial fluid levels were usually less than serum concentrations, but in two RA and four OA patients the ratio was reversed, suggesting local production. Osteocalcin may be an important marker of bone activity in OA.

Adrenal Cortex Hormones↗

Arachidonic acid metabolism in neutrophil granulocytes obtained from synovial fluid in rheumatoid arthritis.

Circulating human neutrophil granulocytes (PMNs) from patients with rheumatoid arthritis (RA) have earlier been described to possess an enhanced capacity for production of certain 5-lipoxygenase-derived metabolites of arachidonic acid (AA), 5-hydroxyeicosatetraenoic acid (5-HETE) and leukotriene B4 (LTB4). In the present investigation the endogenous AA metabolism of synovial fluid PMNs of RA patients was studied and compared with that of the corresponding circulating PMNs. Synovial fluid PMNs prelabelled with 14C-AA released significantly less radioactivity than circulating PMNs when stimulated with calcium ionophore. Furthermore, synovial fluid PMNs produced significantly smaller amounts of both 5-HETE and LTB4 than circulating PMNs from the same patients, whereas no such difference was observed in the LTB4 catabolites or the cyclo-oxygenase products. More information dealing with the complex way in which arachidonic acid is metabolized in diseased RA joints may provide future rational approaches in the treatment of this chronic inflammatory disease.

Adult↗

Measurement of the viscosity of synovial fluid.

An account is given of a viscometer which can be used for measuring the viscosity of synovial fluid when only small quantities are avaliable (0.15 ml) and taking into account the non-Newtonian character of the fluid. A technical description of the apparatus is given. A series of experiments are reported in which bovine synovial fluid was used to study whether and what changes took place in connection with storage, alterations in temperature, and post mortem. It was shown that storage at 4 degrees C for up to 2 weeks did not cause any particular changes, that alterations in temperature from room temperature to body temperature resulted in a moderate decrease in the relative viscosity, and that changes found 6 hours post mortem seemed to be insignificant. The conclusion drawn from the experiments is that the apparatus can be regarded as suitable for use in a more comprehensive study of the changes in viscosity which occur in various joint diseases.

Animals↗

Synovial fluid stimulates the proliferation of rabbit ligament. Fibroblasts in vitro.

This study was designed to test the hypothesis that synovial fluid may be inhibitory to cell proliferation. The effects of bovine synovial fluid (SF) and hyaluronic acid (HA) on the proliferation of normal rabbit medial collateral ligament (MCL), anterior cruciate ligament (ACL), and MCL scar cells were therefore investigated. Cell lines established from rabbit tissues were plated, incubated, and allowed to attach before treatment with varying concentrations of SF, HA, and a balanced salt solution (BSS). The BSS group was added as a control to observe the effects of media dilution alone on cell proliferation. Cell numbers from each group were quantified at 24, 48, 72, and 96 hours. Results showed that for all cell types, cell proliferation during the log phase of growth was significantly stimulated by SF. Maximum stimulation occurred in 20% SF with stimulation decreasing at higher concentrations of SF. HA had virtually no effect on scar and ACL cells, and only a slight stimulatory effect on MCL cells. Media dilution had no effect on scar cells and began to inhibit cell proliferation of ACL and MCL cells only at high dilutions. These findings suggest that low concentrations of bovine SF stimulate proliferation of rabbit ligament and scar fibroblasts in vitro by a mechanism that appears not to involve HA. Even in high concentrations, SF was not inhibitory to proliferation. The implications of these findings to ligament healing and normal ligament physiology require further investigation.

Animals↗

Does joint effusion on T2 magnetic resonance images reflect synovitis? Part 2. Comparison of concentration levels of proinflammatory cytokines and total protein in synovial fluid of the temporomandibular joint with internal derangements and osteoarthrosis.

OBJECTIVE: We sought to clarify the nature of joint effusion (JE) on T2-weighted magnetic resonance images of the temporomandibular joint (TMJ) by analysis of the synovial fluid in the superior compartment of patients with internal derangement and osteoarthrosis. STUDY DESIGN: One hundred symptomatic TMJs (100 patients) with 65 internal derangements and 35 osteoarthroses were scanned by means of magnetic resonance imaging, and, the synovial fluid was sampled on the same day. The amount of JE was evaluated on a scale of 0 to 3. Grades 0 and 1 indicated absence of JE or a negligible amount of JE, respectively, and grades 2 and 3 indicated the presence of JE. Correlation was evaluated among the amount of JE and the concentrations of the total protein and interleukin-1beta(IL-1beta), IL-6, IL-8, and tumor necrosis factor-alpha in the synovial fluid. RESULTS: Magnetic resonance imaging revealed the absence of JE in 40 joints (grade 0, 17 joints; grade 1, 23 joints) and the presence of JE in 60 joints (grade 2, 31 joints; grade 3, 29 joints). The joints with JE had, on average, significantly higher concentrations of total protein (1,675 microg vs 714 microg; P = .0001) and IL-6 (42.9 pg vs 10.6 pg; P = .009) than did the joints without JE. Furthermore, there were significant correlations between the JE grade and the concentrations of the total protein (P = .0001), IL-6 (P = .001), and IL-8 (P = .004). The detection ratio of cytokines among the presence-absence groups of JE showed a significant difference in tumor necrosis factor-alpha (68.3% vs 47.5%; P = .037) and IL-6 (86.7% vs 67.5%; P = .012). Conclusions. JE may contain the released products when there is pronounced synovitis. It is probably composed of high concentrations of total protein with inflammatory cytokines. Furthermore, IL-6 and IL-8 seem to have an important role in the pathogenesis of JE in TMJ disorders.

Adolescent↗

Serum interleukin 8 levels correlate with synovial fluid levels in patients with aseptic loosening of hip prosthesis.

Levels of inflammatory cytokines (tumor necrosis factor alpha, interleukin [IL] 6, and IL-8) in serum from patients with osteolysis on radiographs after hip arthroplasty [osteolysis(+), n = 28], patients without osteolysis after hip arthroplasty [osteolysis(-), n = 24], and nonoperated healthy subjects [controls, n = 20] were determined. In addition, cytokine levels in synovial fluid from patients undergoing revision total hip arthroplasty (n = 14) for loosening were measured and compared with each other and with the area of osteolysis on radiographs. Serum IL-6 and IL-8 levels were significantly higher in the osteolysis(+) group than in the osteolysis(-) or the control groups. Furthermore, a significant correlation was found between the serum and synovial fluid IL-8 levels and between synovial fluid IL-8 levels and the area of osteolysis in patients undergoing revision total hip arthroplasty. Therefore, serum IL-8 levels could be a useful periprosthetic osteolysis marker.

Female↗

Defective phagocytosis by synovial fluid and blood polymorphonuclear leucocytes in patients with rheumatoid arthritis. I. The nature of the defect.

In a series of thirty-seven patients with rheumatoid arthritis (RA), 50% showed a defect of phagocytosis of Candida albicans by synovial fluid polymorphonuclear leucocytes (SF-PMN) and 40% yielded a defect in peripheral blood (PB-PMN). There was a positive correlation between the defective phagocytosis of SF-PMN and PB-PMN suggesting that defective PB-PMN migrate into the synovial fluid. The defect was associated with the lack of a functional C3b receptor on SF-PMN in 64% of patients and on PB-PMN in 40% of patients. SF-PMN or PB-PMN contained intracellular IgG, IgM and C3 in some patients but the presence of these factors could not be correlated with defective phagocytosis of either cell population. There was no correlation between phagocytosis and the differential agglutination test (DAT) ratio of either serum or synovial fluid. The killing of Candida by SF-PMN and BP-PMN was normal. The results could explain the increased susceptibility to joint infection of patients with RA.

Adult↗

Behaviour of effector cells, synovial fluids, and sera from rheumatoid arthritis patients in antibody-dependent cell-mediated cytotoxicity.

Antibody-dependent cell-mediated cytotoxicity (ADCC) was examined in patients with rheumatoid arthritis (RA). The cytotoxicity of peripheral blood leucocytes from patients with RA was similar to that found in normal persons, whereas ADCC was less effective in RA synovial fluid cells. It is possible that the activity in these cells is lower because of immune complexes and other factors being absorbed from the synovial fluid itself. Although patients' sera had little effect on normal peripheral blood leucocytes, synovial fluid from RA patients was markedly inhibitory in ADCC. The degree of inhibition correlated significantly with the clinical status of the patients.

Adult↗

Synovial fluid T cell reactivity against 65 kD heat shock protein of mycobacteria in early chronic arthritis.

The in vitro proliferative response against a recombinant 65 kD Mycobacterium bovis protein that has 100% homology with the 65 kD protein of M tuberculosis was tested in synovial fluid and peripheral blood mononuclear cells from patients with rheumatoid arthritis (RA) and other types of chronic arthritis. An acetone precipitate (AP) of M tuberculosis, and a purified protein derivative (PPD) of M tuberculosis were also tested. Responsiveness of synovial fluid lymphocytes to the mycobacterial antigens was found both in patients with RA and in patients with other forms of chronic inflammatory arthritis, but not among controls. T cell reactivity against mycobacterial antigens was nearly always higher in synovial fluid than in peripheral blood in those patients who showed reactivity. A significant association was found between responsiveness of synovial T cells to the 65 kD protein and AP, but no relation between responsiveness to the 65 kD protein and PPD. Both the number of 65 kD protein responders and the mean proliferative response of synovial T cells to the 65 kD protein were inversely correlated with duration of joint inflammation. Thus, a 65 kD-protein-specific reactivity of synovial T cells, mainly present in an early stage of joint inflammation, may be responsible for triggering chronic arthritis.

Adolescent↗

The distribution of dendritic cells in the synovial fluids of patients with arthritis.

We have investigated the cellular composition of 108 consecutive samples of synovial fluid from patients with Juvenile Chronic Arthritis (JCA), Rheumatoid Arthritis (RA) and Osteoarthritis (OA). Particular emphasis was placed upon the enumeration of cells with dendritic morphology and the study of their in vitro function. Whilst the cellularity of the synovial fluids varied by a factor of greater than 100 within patient groups, the fluids obtained from patients with inflammatory arthritis (JCA & RA) were more cellular than those from patients with non-inflammatory arthritis (OA). This was also noted with respect to both the number and proportion of dendritic cells. The dendritic cells stimulated allogeneic mixed leucocyte reactions, and enhanced mitogenic responses of peripheral blood lymphocytes when present in numbers as low as 1% of the total mononuclear cells. Syngeneic stimulation of blood lymphocytes by similar numbers of dendritic cells was usually negative. However, occasionally there was a marked syngeneic stimulation, which may be evidence for the presentation of antigen by dendritic cells within the arthritic joint.

Arthritis↗

[Artificial synovial fluid for the intra-articular treatment of rheumatoid arthritis and osteoarthritis (chemical synthesis and clinico-experimental and biomechanical data)].

Based on the clinical, experimental and biomechanical studies the authors suggest intraarticular treatment of rheumatoid arthritis (RA) and deforming osteoarthrosis (DOA) by means of artificial synovial fluid (ASF) developed with the use of polymers and biopolymers. Rheological studies performed with the use of a Rheotest-2 apparatus and ultrasonic interferometry of the samples of normal, RA, DOA synovial fluid and ASF demonstrated that medium-molecular-weight polyvinylpyrrolidone (PVP) and PVP hyaluronate appeared the most similar to natural synovial fluid, PVP-hyaluronate, PVP and its complexes with other drugs (cyclophosphamide, hydrocortisone, arteparone) were applied intraarticularly to the treatment of 520 patients with RA and DOA. The group of patients who received kenalog or placebo intraarticularly served as control. Over 3000 intraarticular administrations of ASF and its complexes were made altogether. No side effects were observed. In the articular medium, PVP displayed lubrication, anti-inflammatory, prolonging, anticommissural and other effects. Attention is drawn to the immunoregulatory action of PVP. The treatment with artificial articular lubricants promoted the improvement of the function of the joints and positive time-course of some clinical, laboratory, biochemical and immunological characteristics.

Aged↗