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Predictive value of synovial fluid analysis in estimating the efficacy of intra-articular corticosteroid injections in patients with rheumatoid arthritis.

The predictive relevance of synovial fluid analysis and some other variables for the efficacy of intra-articular corticosteroid injections in 30 patients with rheumatoid arthritis and hydropsy in a knee joint was evaluated in a prospective study. At the onset of the study, the knee joints were aspirated and 30 mg triamcinolone hexacetonide injected intra-articularly. The circumferences and the tenderness scores of the knee joints were measured at onset, after two months, and at the end of the six months' follow up. Of the variables studied, synovial fluid C4, percentage of synovial fluid polymorphonuclear leucocytes, blood haemoglobin, and serum C3 correlated significantly with the decrease in knee joint circumference after two months, whereas only the percentage of synovial fluid polymorphonuclear leucocytes correlated significantly after six months. Between the patients with and without improvement in the tenderness scores of the knee joints, only serum IgM differed at the examination after two months; this was higher in patients whose scores showed no improvement.

Adult↗

Receptor expression in synovial fluid neutrophils from patients with rheumatoid arthritis.

OBJECTIVES: The aim of this study was to determine if neutrophils isolated from the blood and synovial fluid of patients with rheumatoid arthritis had patterns of receptor expression resembling those of blood neutrophils from controls which had been activated and primed in vitro. METHODS: Fluorescence activated cell sorting was used to measure receptor expression in paired blood and synovial fluid neutrophils from patients and in control neutrophils exposed to phorbol myristate acetate and granulocyte-macrophage colony stimulating factor. RESULTS: There was no significant difference in the patterns of receptor expression in blood neutrophils from patients and healthy controls, but neutrophils in the synovial fluid had been primed and activated within the joint. About 50% of rheumatoid synovial fluid neutrophil samples expressed Fc gamma RI, a high affinity receptor for monomeric IgG, which is only expressed in neutrophils exposed to cytokines. CONCLUSIONS: Synovial fluid neutrophils are activated and primed within the inflamed joint and hence their ability to respond to activating factors such as immune complexes will be modulated. As the expression of Fc gamma RI requires active biosynthesis, this work indicates that selective gene activation occurs when neutrophils are recruited into rheumatoid joints.

Antigens, CD↗

Comparative study of normal and osteoarthritic canine synovial fluid using 500 MHz 1H magnetic resonance spectroscopy.

High resolution 1H nuclear magnetic resonance spectroscopy has been used to investigate and compare the metabolic profiles of normal and osteoarthritic synovial fluids in a canine model of osteoarthritis. The spectra of osteoarthritic synovial fluid showed (a) increased concentrations of lactate, pyruvate, lipoprotein-associated fatty acids, and glycerol as well as the ketones hydroxybutyrate and hydroxyisobutyrate, (b) reduced levels of glucose, and (c) elevated levels of N-acetylglycoproteins, acetate, and acetamide compared with healthy normal canine synovial fluid. An increase was also observed in the concentrations of the amino acids alanine and isoleucine. These results suggest that (a) the intraarticular environment in canine osteoarthritis is more hypoxic and acidotic than in a normal joint, (b) lipolysis may play an increasingly important role as a source of energy in osteoarthritis, and (c) the N-acetylglycoprotein polymer component of synovial fluid (mostly hyaluronan) seems to be increasingly fragmented and degraded into acetate by way of an acetamide intermediate with progressive osteoarthritis. The observed changes in the biochemical profile of canine osteoarthritic synovial fluid may be useful in understanding alterations in joint metabolism consequent to arthritic diseases and helpful in identifying potential markers of osteoarthritis.

Animals↗

Assay of synovial fluid parameters: hyaluronan concentration as a potential marker for joint diseases.

Synovial fluids from the knees of patients with degenerative joint disease (n = 29), osteoarthritis (n = 16), diabetic arthropathy (n = 12), gout (n = 7) and acute inflammatory joint disease (n = 7) were investigated by high-performance size-exclusion chromatography combined with multiangle laser light scattering detection and differential refractometry. These data were compared with the viscosities of the same samples measured by rotation viscometry with one low shear rate, as well as with C reactive protein. The median value of the weight-average molecular weight of hyaluronan in synovial fluids, which differed less than the viscosity of these groups, varied between 1.09 x 10(6) g/mol (range 0.849-1.63 x 10(6) g/mol) (acute-inflammatory joint disease) and 1.91 x 10(6) g/mol (range 1.06-3.48 x 10(6) g/mol) (degenerative joint disease). The correlation between viscosity and hyaluronan concentration was much better than between viscosity and weight-average molecular weight. Changes in C reactive protein concentration were correlated with the disease activity. The concentration of hyaluronan was significantly higher in the cases of degenerative joint disease and diabetic arthropathy. These results suggest that synovial fluid concentration of hyaluronan is appropriate as a prognostic value in the evaluation of different kinds of joint diseases.

Biomarkers↗

Joint size influence on the leucocyte count of inflammatory synovial fluids.

The mean leucocyte count (LC) of the synovial fluid (SF) obtained from 22 elbow joints of patients with chronic inflammatory polyarthritides was 23.4 +/- 17.8 x 10(9)/l while the mean LC of the SF from their paired larger knee joints with similar degree of clinically detectable inflammation was 10.9 +/- 9.9 x 10(9)/l (p less than 0.001). The mean of the ratios between the LC of the paired joints (LC elbow/LC knee) was 2.92 +/- 2.07, above the ratio 1.0 (p less than 0.001) which would be expected if the LCs of both joints were similar. Different sizes of the paired joints presumably explained the phenomenon, which may be due to dilution factors. The size of the joint should be considered when interpreting the leucocyte counts of synovial fluid.

Elbow Joint↗

An immunochemical study of the synovial fluid can contribute to the distinction between rheumatoid and non rheumatoid arthritis.

Synovial fluids from 102 patients affected by various joint diseases have been analyzed for their protein, immunoglobulin and beta 2-microglobulin contents, for the total and alternative pathway hemolytic activities of the complement components, for the presence of rheumatoid factors and Clq binding materials. The aim of this study was to verify whether an immunochemical analysis of the synovial fluid could help to distinguish rheumatoid arthritis from other arthropathies. With regard to this, we emphasize that the latex test, the Clq binding assay, as well as the measurement of C3d and beta 2-microglobulin concentrations in synovial fluids, were the most helpful assays. An immunochemical synovial score was calculated summing the results of these four tests, thus making the recognition of rheumatoid arthritis, among the various inflammatory joint diseases, easier.

Arthritis↗

Quantitative analysis of hyaluronan in human synovial fluid using capillary electrophoresis.

The glycosaminoglycan, hyaluronan, can be detected in human synovial fluid by capillary electrophoresis (CE). Variations in peak shape make this technique unsuitable for quantitative analysis of hyaluronan in raw synovial fluid. Quantitative analysis was achieved by hydrolysis of the polymeric hyaluronan to the tetrasaccharide by the action of testicular hyaluronidase and separation of the product using CE. A UV detector operating at 200 nm was used. The X-ray contrast material, omnipaque, a propriety aqueous solution of iohexol was used as internal standard. A second peak in the electropherogram of synovial fluid was quantified. The variation in concentrations of these two components correlate with the arthritic disease state of a joint.

Arthritis, Rheumatoid↗

[Time required for replenishment of synovial fluid under experimental conditions].

Experimental data to determine time for restoration of intraarticular fluid are presented. Mature healthy domestic goats served as experimental animals. From the carpal joints under sterile conditions, synovial fluid was sucked out as completely as possible. Every four hours during the first day and further in 2, 3, 4 days synovial fluid was taken from one of the joints. Cellular elements, their percentage, pH, viscosity (determined on the amount of hyaluronic acid), common proteins and their fractions were determined. It was demonstrated that the process of synovial fluid restoration, in case it was removed completely, took four days. At first the amount of synovial fluid is restored at the expense of its liquid part, percentage of common protein and its fractions increase, and viscosity of synovial fluid decreases. After two days, a gradual restoration of all physiological indices mentioned occurs. By the fourth day they are completely restored. Data of synoviogram demonstrate that at first blood cells appear in a great amount, while cells of tissue origin are very scanty, and by the fourth day percentage of cellular elements is equal to the original: cells of tissue origin--70-72%, blood cells--28--30%.

Animals↗

Correlation of prostaglandin E2 concentrations in synovial fluid with ground reaction forces and clinical variables for pain or inflammation in dogs with osteoarthritis induced by transection of the cranial cruciate ligament.

OBJECTIVE: To evaluate the temporal pattern of prostaglandin (PG) E2 concentrations in synovial fluid after transection of the cranial cruciate ligament (CCL) in dogs and to correlate PGE2 concentrations with ground reaction forces and subjective clinical variables for lameness or pain. ANIMALS: 19 purpose-bred adult male Walker Hounds. PROCEDURE: Force plate measurements, subjective clinical analysis of pain or lameness, and samples of synovial fluid were obtained before (baseline) and at various time points after arthroscopic transection of the right CCL. Concentrations of PGE2 were measured in synovial fluid samples, and the PGE2 concentrations were correlated with ground reaction forces and clinical variables. RESULTS: The PGE2 concentration increased significantly above the baseline value throughout the entire study, peaking 14 days after transection. Peak vertical force and vertical impulse significantly decreased by day 14 after transection, followed by an increase over time without returning to baseline values. All clinical variables (eg, lameness, degree of weight bearing, joint extension, cumulative pain score, effusion score, and total protein content of synovial fluid, except for WBC count in synovial fluid) increased significantly above baseline values. Significant negative correlations were detected between PGE2 concentrations and peak vertical force (r, -0.5720) and vertical impulse (r, -0.4618), and significant positive correlations were detected between PGE2 concentrations and the subjective lameness score (r, 0.5016) and effusion score (r, 0.6817). CONCLUSIONS AND CLINICAL RELEVANCE: Assessment of the acute inflammatory process by measurement of PGE2 concentrations in synovial fluid may be correlated with the amount of pain or lameness in dogs.

Analysis of Variance↗

Magnetic resonance imaging of temporomandibular joint synovial fluid collection and disk morphology.

OBJECTIVE: The purpose of this study was to determine the features of synovial fluid, the shape of the disk, and the presence of disk displacement without reduction (DDsR) of the temporomandibular joint. STUDY DESIGN: A total of 612 bilateral temporomandibular magnetic resonance images of 306 patients were reviewed. The status of the joint was categorized as follows: normal disk position, disk displacement with reduction, acute DDsR, subacute DDsR, and chronic DDsR. The disk shape was characterized as one of following: biconcave, cap-shaped, cup-shaped, flattened, eyeglass-shaped, amorphous, or discontinuous. The amount of synovial fluid was divided into 4 categories: not observed, small, moderate, or large. RESULTS: Synovial fluid collection was observed more frequently with subacute DDsR and when the disk was a folded shape. CONCLUSION: Synovial fluid collection, which was observed on T2-weighted magnetic resonance images, is more frequent in the early stage of DDsR. In addition, high signal intensity within the disk space should be considered a simple matter of fluid collection.

Acute Disease↗

Cephalothin and cefamandole penetration into bone, synovial fluid, and wound drainage fluid.

UNLABELLED: Concentrations of cephalothin or cefamandole were measured in serum, bone, synovial fluid, and wound drainage fluid in fifty-seven patients undergoing total hip or knee replacement after a two-gram intravenous bolus injection. The concentrations were similar in serum and synovial fluid for both antibiotics; however, in bone and drainage fluid the concentration of cefamandole was higher by a factor of three. Concentrations of the same antibiotic at the hip and knee were not significantly different even though a tourniquet was used for the knee replacement procedures. CLINICAL RELEVANCE: The antibiotics penetrate bone and enter synovial fluid so rapidly that it is unnecessary to administer prophylactic antibiotics prior to the time of surgery.

Body Fluids↗

The potential and limitations of cartilage-specific (V+C)(-) fibronectin and cartilage oligomeric matrix protein as osteoarthritis biomarkers in canine synovial fluid.

OBJECTIVE: To determine if levels of the cartilage-specific (V+C)(-) fibronectin isoform in the synovial fluid is associated with cartilage change during osteoarthritis. DESIGN: Synovial fluid was collected from 26 healthy dogs presenting to the Orthopedic Surgery Clinic with unilateral cranial cruciate rupture, 22 control dogs, and 13 dogs from a colony maintained for the study of canine hip dysplasia. Total fibronectin, (V+C)(-) fibronectin, and cartilage oligomeric matrix protein (COMP) were quantitated by ELISA assays. Statistical analysis used Wilcoxon's signed-rank and rank-sum tests and Spearman's rank correlation. RESULTS: The concentration of total fibronectin was increased in affected (P<0.0001) and contralateral (P=0.0005) knees of the clinic population (compared to unaffected knees in colony controls). Both (V+C)(-) fibronectin and COMP concentrations were elevated in the contralateral knees in clinical patients relative to unaffected knees in the colony controls (P=0.03 and P=0.04, respectively), and relative to the affected knees (P=0.003); however, corrections for joint effusions suggest elevated totals in the affected knees. (V+C)(-) fibronectin and COMP concentrations were correlated (r(sp)=0.74; P<0.0001) in 30 unaffected knees of patients and colony controls. Total fibronectin was correlated negatively with months since the initial injury (r(sp)=-0.44; P=0.03) in the affected joints. The intraoperative lesion severity score did not correlate with total fibronectin or (V+C)(-) fibronectin (P>or=0.35). CONCLUSIONS: Concentration of total fibronectin in synovial fluid might be a useful biomarker for cross-sectional studies in osteoarthritis, but only (V+C)(-) fibronectin provides information specifically about cartilage damage. Elevated concentrations of (V+C)(-) fibronectin and COMP seen in the contralateral knees of patients with cranial cruciate rupture might indicate cartilage changes early in the disease process (pre-clinical). However, the wide range of values obtained limits the diagnostic value for any one individual. Joint effusions obscure the total amount of biomarkers in affected synovial joints.

Animals↗

Modulation of phospholipase A2 activity in human synovial fluid by cations.

Cell-free, Ca2+-dependent phospholipase A2 activity (PLA2) was measured in human synovial fluid of patients with various kinds of arthritis using [1-14C] oleate-labelled autoclaved Escherichia coli as substrate. PLA2 activity at pH 7.0 and with 5 mM added Ca2+ was stimulated and then inhibited in a dose-dependent fashion by NaCl; maximal stimulation of 8.8 fold was found at 150 mM Na+. Similar effects were obtained with K+, Li+ and Ru+. In the absence of added Na+, PLA2 activity was maximal with 25 mM Ca2+ (145 nmols/hr/mg), but in the presence of 150 mM Na+, activity was maximal with 4 mM Ca2+ (415 nmols/hr/mg). PLA2 activity was optimal between pH 6.5-8.0 in presence of 150 mM Na+1 and 4 mM Ca2+. There was no significant difference between PLA2 activity in synovial fluids from rheumatoid and other types of arthritis. Neutral active, Ca2+-dependent PLA2 activity in acid extracts of human platelets, plasma, polymorphonuclear leukocytes and synovial fluid varied in response to added Na+. In presence of 150 mM added Na+ and 5 mM Ca2+, PLA2 activity in human synovial fluid was inhibited by all multivalent cations tested. In the absence of Na+, Cu2+ and Mg2+ stimulated PLA2 activity in a dose dependent fashion; whereas, Fe2+, Fe3+ and Al3+ were inhibitory. The extent of stimulation by Mg2+ was inversely related to the concentration of added Ca2+.

Arthritis↗

1H-nuclear magnetic resonance studies of human synovial fluid in arthritic disease states as an aid to confirming metabolic activity in the synovial cavity.

1. A 1H-n.m.r. method was used to measure concentrations of valine, alanine, lactate, acetate, hyaluronan and lipids in synovial fluid obtained, during the normal course of examination from the knee joints of patients attending rheumatology and orthopaedic clinics. Fluid was available from 16 patients with osteoarthritis, 18 patients with rheumatoid arthritis, four patients with meniscal tear and one patient each with systemic lupus erythematosis, mono-arthritis, synovitis and loose bodies. Four normal specimens were obtained for comparison. 2. Valine, alanine and acetate levels all showed a normal Gaussian distribution, reflecting the distributions within the serum of the sample population. 3. Lactate concentrations divided into two distinct patterns. At concentrations below 2.5 mmol/l the lactate levels showed a Gaussian distribution, reflecting the distribution in normal serum. The normal synovial fluid specimens belong to this distribution. Above 2.5-3.0 mmol/l, lactate levels were asymmetric in distribution with a long tail at higher concentrations. These high levels of lactate can be explained by the generation of lactate through anaerobic metabolism within the synovial cavity. This metabolic process is triggered by a general inflammatory condition such as in rheumatoid arthritis. 4. The distribution of n.m.r.-observable lipid concentrations in rheumatoid arthritis and osteoarthritis each shows a normal distribution and the mean concentration is significantly higher in rheumatoid arthritis. 5. An increased n.m.r.-observable hyaluronan concentration is associated with an inflammatory situation. 6. It is concluded that raised levels of lactate and n.m.r.-observable hyaluronan and lipids are useful markers to aid the clinical distinction between rheumatoid arthritis and osteoarthritis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗

Synovial fluids facilitate small solute diffusivity.

The diffusivity of water, fucose, proline, lysine, glutamic acid, glucose and sucrose was determined in a variety of inflammatory human synovial fluids. In view of the constituents of pathological synovial fluids one would predict impedence to solute movement. In several fluid diffusivity was enhanced relative to translational diffusion in water. In most fluids diffusivity was enhanced relative to diffusion in diluted serum. Diffusivity of the solutes was dependent on size and charge of the solute but independent of fluid characteristics, including glucose, protein, and complement concentrations and cellular constituents. This paper reports aberrant small solute behaviour in synovial fluids. Enhanced diffusivity relative to water was demonstrated in hyaluronate dissolved in diluted serum as well. Hyaluronate domains in the synovial fluids interact with these solutes, facilitating movement. This phenomenon affords a homoestatic mechanism as regards chondrocyte viability in spite of inflammation or a low glucose concentration.

Arthritis↗

Supravital staining of cells in noninflammatory synovial fluids: analysis of the effect of crystals on cell populations.

Leukocyte differential counts are rarely performed on synovial fluids (SF) with low leukocyte (WBC) counts as they have been difficult to do with standard Wright stains. We performed SF analysis including supravital (SV) stains for differential counts on 100 consecutive relatively noninflammatory synovial fluids defined as any SF with less than 2,000 cells/mm3. SV stains gave clear cellular morphology. Monocytes were the most prominent cells in all noninflammatory synovial fluids. Thirty-eight fluids were found to have crystals (monosodium urate (MSU) in 15, calcium pyrophosphate dihydrate (CPPD) in 5, CPPD plus apatite-like crystals in 9, apatite-like clumps alone in 8 and lipid liquid in 1). WBC counts, percentages of polymorphonuclear (PMN) and absolute PMN counts were greatest in fluids with MSU or CPPD crystals. Fluids with apatite-like clumps alone tended to have the lowest WBC counts. The presence of WBC over 500 cells/mm3, over 20% PMN and absolute PMN counts over 250 cells/mm3 should encourage a careful search for crystals, especially MSU, in noninflammatory synovial fluids.

Apatites↗

Chick "crooked-toe" syndrome induced by polar lipid in synovial fluids from some rheumatoid arthritis patients.

Injection into fertile chicken eggs of synovial fluids from some rheumatoid arthritis patients resulted in either embryo death or the development of the "crooked-toe" (CT) syndrome, or both, in newly hatched chicks. Synovial fluids from most RA patients (and fluids from a few non-RA individuals), however, were harmless. Dialyzing, partitioning, and gel filtration experiments indicated that the CT syndrome-inducing factor consists of 1 or more heat stable, dialyzable, polar lipids with molecular weights of about 3 to 4 x 10(3). Thin-layer chromatography revealed quantitative and qualitative differences between partially purified lipid preparations from "active" and "inactive" synovial fluids.

Animals↗

Estimation & significance of serum & synovial fluid malondialdehyde levels in rheumatoid arthritis.

Serum and synovial fluid (SF) levels of malondialdehyde (MDA), a marker of free radical induced lipid peroxidation, were estimated in patients of rheumatoid arthritis (RA) and compared with healthy controls and patients of osteoarthritis (OA). While serum MDA levels were similar in healthy controls (0.24 +/- 0.10 nmol/ml) and OA (0.28 +/- 0.11 nmol/ml), the serum levels in RA (0.47 +/- 0.19 nmol/ml) were significantly higher as compared to both healthy controls and OA patients; and correlated with synovial fluid (SF) MDA levels. No difference was observed in SF-MDA levels in RA (0.17 +/- 0.07 nmol/ml) and OA (0.16 +/- 0.09). MDA levels did not correlate with markers of disease activity in RA like joint counts, duration of morning stiffness, erythrocyte sedimentation rate etc. Increased serum MDA levels in RA suggest the role of free radicals in the pathogenesis of this inflammatory arthropathy and support the need for further studies assessing the therapeutic role of free radical scavengers in RA.

Arthritis, Rheumatoid↗