Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
12806976 [A case of sarcoidosis overlapping with rheumatoid arthritis]. 2003 We report the case of a 54-year-old woman who presented on May 28, 2001 with sarcoidosis overlapping with rheumatoid arthritis. She had experienced morning stiffness 2 years previously and was diagnosed as having rheumatoid arthritis. She had been treated with bucillamine and loxoprofen for 3 months. In October 2000, she developed proteinurea. The patient discontinued treatment with bucillamine and loxoprofen. Proteinurea persisted, and the patient's renal function declined. On admission, subcutaneous nodules were palpable in the patient's legs. The patient's serum creatinine and calcium levels were 2.49 mg/dl and 11.6 mg/dl, respectively. Intact-PTH was suppressed, and PTHrP was not elevated. Despite the presence of hypercalcemia, the patient's serum 1 alpha 25(OH)2D3 was not suppressed. Serum ACE and lysozyme levels were elevated beyond the normal ranges. A renal biopsy was performed, and non-caseous epithelioid granuloma was found in the renal interstitium. Based on the histological findings, the patient was diagnosed as having sarcoidosis. Following treatment with prednisolone, the patient's serum calcium levels returned to normal and her renal function improved.
12898307 Coronal laxity in extension in vivo after total knee arthroplasty. 2003 We performed stress arthrometric studies on 77 knees (71 patients) with total knee arthroplasty to determine the presence and magnitude of femoral abduction and adduction in knee extension. A total of 53 knees (49 patients) had posterior cruciate ligament-retaining (PCLR) prostheses, and 24 (22 patients) had PCL-substituting (PCLS) prostheses. The selected patients had successful arthroplasties with no clinical complications a minimum of 5 years after primary surgery. Each patient was subjected to a successive abduction and adduction stress test at 0 degrees -20 degrees of flexion using a Telos arthrometer. The mean values for abduction and adduction were 4.8 degrees and 4.5 degrees with a PCLR prosthesis, respectively, and 4.6 degrees and 4.0 degrees with a PCLS prosthesis. There were no statistical differences between PCLR and PCLS knees. The results suggest that approximately 4 degrees of laxity in these directions is suitable in total knee arthroplasty for a satisfactory clinical outcome 5-9 years after surgery.
12810997 Cutaneous metaplastic synovial cyst. 2003 Jun Metaplastic synovial cyst of the skin is a recently recognized entity characterized by an intradermal nodule that usually occurs at the site of previous surgical trauma. Histologically, the lesion demonstrates a cystic structure with villous-like projections and a lining resembling hyperplastic synovium. We have studied two patients with rheumatoid arthritis, aged 46 and 55 years, who presented with cystic nodules localized on the thumb and great toes, respectively, without any history of previous trauma or surgical procedures performed in the areas. The presence of vimentin and CD 68 positivity of the cells lining the cyst walls supports the similarities between normal and metaplastic synovium. We hypothesize that constant pressure on the great toe, repeated manipulation of the finger, and chronic inflammation around the affected joints may have played roles in the pathogenesis of the lesions in our patients.
12163948 Cardiac damage from chronic use of chloroquine: a case report and review of the literature 2002 Jul Chloroquine has been widely used in rheumatological treatment, but potential severe side effects require careful follow-up. Cardiac damage is not a common consequence, but its clinical relevance has not yet been described. We report the case of a 58-year-old woman with rheumatoid arthritis, in whom chronic chloroquine use resulted in major irreversible cardiac damage. She presented with syncopal episodes due to complete atrioventricular block confirmed by electrophysiological study whose changes were concluded to be irreversible and a permanent pacemaker was indicated. Endomyocardial biopsy was also performed to search for histopathological and ultrastructural cardiac damage. We also reviewed the 22 cases of chloroquine-induced cardiopathy described to date as well as its pathophysiology.
15552529 Safety issues related to emerging therapies for rheumatoid arthritis. 2004 Sep Several novel biologic therapies for rheumatoid arthritis (RA) are emerging that target aspects of the immune system other than tumor necrosis factor (TNF). Two such therapies currently in development include CTLA4Ig (Abatacept) and anti-CD20 monoclonal antibody (Rituximab). CTLA4Ig has been demonstrated to be well tolerated with a good short-term safety profile. Rituximab has also been shown to have a good safety profile in a limited number of RA patients. Further safety data with larger numbers of RA patients treated with Rituximab is required.
14872485 Interleukin-18 enhances monocyte tumor necrosis factor alpha and interleukin-1beta product 2004 Feb OBJECTIVE: At sites of inflammation, T cells exert pathologic effects through direct contact with monocyte/macrophages, inducing massive up-regulation of interleukin-1 (IL-1) and tumor necrosis factor alpha (TNFalpha). We examined the regulatory effects of IL-18 on monocyte activation by direct contact with T lymphocytes in rheumatoid arthritis (RA). METHODS: Activated T cells were isolated from RA synovial fluid. Resting T cells and monocytes were isolated from peripheral blood mononuclear cells. RA synovial T cells or phytohemagglutinin (PHA)-stimulated T cells were fixed by paraformaldehyde and then cocultured with monocytes at a ratio of 4:1. Levels of TNFalpha, IL-1beta, IL-10, and IL-18 were measured by enzyme-linked immunosorbent assay. Expression of adhesion molecules, IL-18 receptor, and TNF receptors was analyzed by flow cytometry. Expression of NF-kappaB p65, phosphorylated IkappaBalpha, and phosphatidylinositol 3-kinase (PI 3-kinase) p110 was analyzed by Western blotting. RESULTS: IL-18 dose-dependently enhanced the production of IL-1beta and TNFalpha, but not IL-10, by monocytes following contact with RA synovial T cells or PHA-prestimulated T cells. NF-kappaB inhibitors N-acetyl-L-cysteine and Bay 11-7085 and PI 3-kinase inhibitor LY294002 inhibited the enhancing effects of IL-18, but MAPK p38 inhibitor SB203580, ERK inhibitor PD98059, and JNK inhibitor SP600125 did not. Increased levels of NF-kappaB in the nucleus, phosphorylated IkappaB, and PI 3-kinase were confirmed in monocytes cocultured with PHA-prestimulated T cells, and the levels were further increased by stimulation with IL-18. Neutralizing antibody to IL-18 inhibited monocyte activation induced by direct contact with PHA-prestimulated T cells. Via cell-cell contact, PHA-prestimulated T cells increased autocrine production of IL-18 by monocytes, which was mediated by activation of the NF-kappaB and PI 3-kinase pathways, and up-regulated the expression of the IL-18 receptor in monocytes. IL-18 up-regulated the expression of the TNF receptors vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) on monocytes. Blocking the binding of the TNF receptors VCAM-1 or ICAM-1 on monocytes to their ligands on stimulated T cells suppressed the IL-18-enhanced production of TNFalpha and IL-1beta in monocytes induced by contact with PHA-prestimulated T cells. CONCLUSION: IL-18 augments monocyte activation induced by contact with activated T cells in RA synovitis, which is dependent on activation of the NF-kappaB and PI 3-kinase pathways. IL-18 up-regulates the expression of the TNF receptors VCAM-1 and ICAM-1 on monocytes, which mediate the enhancing effects of IL-18 on T cell-monocyte contact.
11879242 Changes in lymphocytic cluster distribution during extracorporeal immunoadsorption. 2002 Feb The success of apheresis treatment is often measured as a decrease in the detected antibodies and an improvement in different disease-related scores. Sometimes, however, the seriousness of the disease does not correlate with the antibody level. During a period of 8 years, 15 patients (3 myasthenia gravis, 1 multiple sclerosis, 2 systemic lupus erythematosus, 3 alloimmunized kidney transplant, 6 rheumatoid arthritis) were treated by protein A immunoadsorption. Lymphocyte subpopulations (activated T cells, cytolytic T cells, B cells, natural killer cells) and inflammatory proteins (ferritin, C-reactive protein, alpha1-antitrypsin, alpha2-macroglobulin) were analyzed. After observing clinical outcomes, the patients could be divided into 2 groups, respectively: Group 1, responding patients with remission of disease; and Group 2, delayed-responding patients, who required chronic treatment. Group 1 patients characteristically showed a greater increase in activated T and cytolytic T cells which correlated with a greater decrease of B cells. It might be possible that protein A immunoadsorption induced immunomodulation. Further immunological investigation is required to verify these findings.
15573865 Selective retinoic acid receptor ligands for rheumatoid arthritis. 2004 Nov Retinoids, modulators of retinoic acid receptors (RARs), have been studied for over 20 years as potential therapeutic agents for rheumatoid arthritis (RA). Early successes at the in vitro and in vivo levels were overshadowed by disappointing clinical trials that yielded poor efficacy and unacceptable side effects. A greater understanding of retinoid biology has led to the development of many synthetic retinoids that selectively modulate the RAR isotypes. RAR selective retinoids have a high potential for improved pharmacology with reduced toxicity, thereby renewing interest for the use of retinoids in RA.
15248208 Association between HLA class II genes and autoantibodies to cyclic citrullinated peptides 2004 Jul OBJECTIVE: The functional role of HLA class II molecules in the pathogenesis of rheumatoid arthritis (RA) is unclear. HLA class II molecules are involved in the interaction between T and B lymphocytes required for long-lived B cell responses and generation of high-affinity IgG antibodies. We undertook this study to investigate the relationship between HLA class II gene polymorphisms and RA-specific IgG antibodies against cyclic citrullinated peptides (anti-CCP antibodies). METHODS: High-resolution HLA-DR and DQ typing and anti-CCP-2 antibody testing were performed on 268 RA patients from the Early Arthritis Clinic cohort at the Department of Rheumatology of the Leiden University Medical Center. The presence of anti-CCP antibodies was analyzed in carriers of the different DR and DQ alleles. Disease progression was measured over a period of 4 years by scoring radiographs of the hands and feet using the Sharp/van der Heijde method. RESULTS: Carriership of the individual alleles HLA-DRB1*0401, DRB1*1001, DQB1*0302, and DQB1*0501 was associated with the presence of anti-CCP antibodies. Carriers of DQ-DR genotypes containing proposed RA susceptibility alleles were significantly more often anti-CCP antibody positive. Carriership of one or two HLA-DRB1 shared epitope (SE) alleles was significantly associated with production of anti-CCP antibodies (odds ratio [OR] 3.3, 95% confidence interval [95% CI] 1.8-6.0 and OR 13.3, 95% CI 4.6-40.4, respectively). An increased rate of joint destruction was observed in SE+, anti-CCP+ patients (mean Sharp score 7.6 points per year) compared with that in SE-, anti-CCP+ patients (2.4 points per year) (P = 0.04), SE+, anti-CCP- patients (1.6 points per year) (P < 0.001), and SE-, anti-CCP- patients (1.6 points per year) (P < 0.001). CONCLUSION: HLA class II RA susceptibility alleles are associated with production of anti-CCP antibodies. Moreover, more severe disease progression is found in RA patients with both anti-CCP antibodies and SE alleles.
12183791 [Shoulder arthroplasty - Clinical results in 171 patients]. 2002 Jul AIM: Review and critical evaluation of 181 shoulder arthroplasties performed on 171 patients between December 1992 and January 1997. METHOD: We performed 118 hemiarthroplasties and 63 total shoulder replacements in 171 patients with an average age of 56.5 years. The patients were examined clinically and radiologically before surgery and followed-up for an average of two years. The Constant score was used for postoperative functional assessment. RESULTS: 46 % of the patients were very satisfied and 31 % were satisfied with the outcome. We found a significant pain reduction and an improvement of active joint function. The average Constant score was 34.9 preoperatively and 65.2 postoperatively. Overall, we found the best results after joint replacement in patients treated for avascular necrosis or fracture sequelae of the humeral head. A revision surgery had to be performed in 16 patients (8.8 %). CONCLUSION: The results of this study are encouraging and underline the growing importance of shoulder arthroplasty. The preoperative limited range of motion, previous surgeries, and the status of the rotator cuff are preoperative indicators for a favourable postoperative outcome. Preoperative planning, anatomical reconstruction, and an optimal rehabilitation programme are the keys for successful shoulder arthroplasty.
12624799 [Imaging techniques in rheumatology: sonography in rheumatoid arthritis]. 2003 Feb Musculoskeletal ultrasonography has become an important diagnostic tool in rheumatoid arthritis. In Germany it is part of the rheumatology training, and many ultrasound courses provide further education. Only in the last five years the international importance of ultrasound in rheumatology has increased dramatically. Sonography can be performed as a bedside procedure and as an extension of the clinical investigation. It is easily tolerated by the patients, and it can be repeated any time. Sonography can have a great impact on therapeutic decisions. A > or = 5 MHz linear transducer is needed. Most transducers that are used for musculoskeletal ultrasound have about 7.5 MHz. Modern transducers with higher frequencies (>7.5 MHz) and high resolution improve the diagnostic value of the investigation. Sonography is superior to plain radiography to detect erosions as far as the region is accessible by ultrasound. It is more sensitive than the clinical investigation for the detection of synovitis, tenosynovitis, tendinitis, and bursitis as well as for the differentiation of these lesions. Color Doppler sonography aids in evaluating the activity of inflammation and in differentiating intraarticular structures. Carpal- and ulnar neuropathy occur secondary to rheumatoid arthritis and may lead to characteristic nerve swelling. Ultrasound-guided injections into joints and tendon sheets can be performed.
14568176 Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry in clinical c 2003 Nov Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-Tof-MS) has recently become a popular and versatile method to analyze macromolecules from biological origin. In this paper, we will review the application of MALDI-Tof-MS in clinical chemistry and biology. MALDI-Tof-MS is used in clinical chemistry, e.g. disease markers can be identified with MALDI-MS analysis in combination with 1-D and 2-D gel electrophoresis separations thanks to either peptide mass fingerprinting (PMF) or peptide sequence tag (PST) followed by data base searching. In microbiology, MALDI-Tof-MS is employed to analyze specific peptides or proteins directly desorbed from intact viruses, bacteria and spores. The capability to register biomarker ions in a broad m/z range, which are unique and representative for individual microorganisms, forms the basis of taxonomic identification of bacteria by MALDI-Tof-MS. Moreover, this technique can be applied to study either the resistance of bacteria to antibiotics or the antimicrobial compounds secreted by other bacterial species. More recently, the method was also successfully applied to DNA sequencing (genotyping) as well as screening for mutations. High-throughput genotyping of single-nucleotide polymorphisms has the potential to become a routine method for both laboratory and clinical applications. Moreover, posttranscriptional modifications of RNA can be analyzed by MALDI using nucleotide-specific RNAses combined with further fragmentation by post source decay (PSD).
14699983 Nerve growth factor, human skin ulcers and vascularization. Our experience. 2004 Cutaneous wound is known to elicit a series of typical cellular responses that include clotting, inflammatory infiltration, reepithelialization, the formation of granulation tissue, including new blood vessel, followed by tissue remodeling and wound contraction. The regulatory molecules implicated in these events are not well known. Neurotrophins and their receptors are trophic factors that are known to play important roles in cutaneous tissues, nerve development and reconstruction after injury. Among the neurotrophins, the nerve growth factor (NGF) was one of the earliest used for clinical studies. NGF has been tested for potential therapeutic application in neuropathies of the central and peripheral nervous system and more recently in human corneal and cutaneous ulcers. Here, I present and discuss data obtained in the last few years on the healing action of NGF in human and domestic animal skin ulcers.
15485996 Expression and localisation of the new metalloproteinase inhibitor RECK (reversion inducin 2005 Mar OBJECTIVE: To assess the expression and localisation of the new metalloproteinase inhibitor RECK, an inhibitor of matrix metalloproteinase-14 (MMP-14) secretion and activity, in the synovial membrane of patients with rheumatoid arthritis (RA). METHODS: RECK expression in synovium samples from patients with RA, osteoarthritis (OA), and "trauma" were studied by quantitative real time reverse transcription-polymerase chain reaction (Q-PCR). RECK mRNA levels were compared with those of the enzyme MMP-14. RECK expression on cryostat sections of synovium was disclosed by goat-antihuman RECK monoclonal antibody. RECK protein was detected on synovial cryostat sections and measured by western blotting. RECK expression on macrophages was investigated by double staining of CD68 and RECK on cryostat sections and characterised by confocal microscopy. RECK expression on RA monocytes or normal monocytes was further investigated by FACS analysis. RESULTS: RECK expression in the synovial membrane of patients with RA was significantly lower than in OA and controls. MMP-14 mRNA levels were not significantly different between the three groups. In RA synovium, RECK protein was expressed mainly in the lining layer but also by macrophages around blood vessels. Fibroblasts and about 50% of the CD68 positive macrophages expressed RECK. In CD68 positive macrophages, RECK was only expressed in secretory granules and not on the membrane. The same pattern was found in M-CSF cultured macrophages of patients with RA and controls. In contrast, synovial fibroblasts showed a diffuse membrane expression within the synovium similar to cultured RA fibroblasts. RECK expression was low on the membrane of monocytes according to FACS analysis. CONCLUSION: The new MMP inhibitor RECK is expressed in synovial membranes of RA, OA, and controls. RECK mRNA is lowest in RA synovial membranes. In contrast with fibroblasts, macrophages in the synovium express RECK only cytoplasmically and not on their membrane.
11927756 Clinical outcomes following a trial of sertraline in rheumatoid arthritis. 2002 Jan We report an open-label trial of sertraline in the treatment of major depression in 54 consecutive rheumatoid arthritis (RA) patients meeting DSM-IV criteria for major depressive disorder. We initially surveyed 628 RA outpatients with the Center for Epidemiologic Studies Depression Scale (CES-D) and invited those with depression to be evaluated further and treated. Eighty-four RA patients reporting depressive symptoms agreed to participate in person, and 56 met the criteria for major depressive disorder. Of these 56 patients, 54 agreed to medication treatment and were enrolled in the study. Patients were also randomized to one of three psychological treatment conditions, but for this study, conditions were collapsed because previous research on this sample indicated no significant between-group differences in depression after treatment. Patients were assessed with the CES-D and the Hamilton Rating Scale for Depression after the intervention, at 6-month follow-up, and at 15-month follow-up. At the last follow-up, 41 patients remained for assessment. In this study, sertraline was found to be a safe and efficacious treatment of depression complicating RA.
12634939 Early rheumatoid arthritis patients: relationship of age. 2003 Mar The aim of this study was to investigate if age at disease onset comprises a separate parameter for disease expression, prognosis, and outcome in early rheumatoid arthritis (RA) patients. Four hundred thirty-eight patients with early RA (disease duration less than 1 year) were studied. All of them fulfilled the American College of Rheumatology criteria for RA. The demographic, clinical, laboratory, radiologic, and therapeutic characteristics of the disease at diagnosis and during and at the end of follow-up (time period 1981-2000) were analyzed according to age at disease onset (young patients aged less than 60 years at disease onset vs elderly patients aged more than 60 years at disease onset). We found 317 young and 121 elderly patients with early RA. The male:female ratio, which was 1:3.2 in the young patients, was nearly equal in the elderly (1:1.4). In addition, at disease onset elderly patients showed more severe joint involvement (decreased grip strength) associated with high titers of acute phase response (erythrocyte sedimentation rate and C-reactive protein) than the younger patients. However, there were no differences between the two groups in the numbers of tender and swollen joints or acute phase response at the end of the study period. Furthermore, no differences were seen between the two groups concerning the presence of rheumatoid factor. Finally, the two patient groups showed the same degree of radiological changes and functional ability and were treated similarly, except for more frequent corticosteroid use in the elderly. We conclude that elderly patients present with more severe joint involvement at disease onset. However, at the end of the study, no differences were seen concerning radiological changes and functional ability. It seems that age at disease onset does not influence the clinical course and outcome of early RA patients.
12355480 CD13/aminopeptidase N-induced lymphocyte involvement in inflamed joints of patients with r 2002 Sep OBJECTIVE: We previously showed that CD13/aminopeptidase N (EC 3.4.11.2) induces chemotactic migration of T lymphocytes by its enzymatic activity. In this study, we examined the role of CD13/aminopeptidase N in lymphocyte involvement in rheumatoid arthritis (RA). METHODS: Synovial fluids were obtained from 27 RA patients and 6 osteoarthritis (OA) patients. Synovial tissue specimens were obtained from 3 RA patients and 3 OA patients. Protease activity of aminopeptidase in synovial fluids and synovial fibroblasts was assayed fluorometrically using the specific substrate. Expression of CD13/aminopeptidase N in synovial fibroblasts was determined by flow cytometry analyses, Western blotting, and reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: The mean value of aminopeptidase activity in synovial fluid samples from RA patients was significantly higher than that in samples from OA patients. Increased enzymatic activity of aminopeptidase was detected on synovial fibroblasts from RA patients compared with those from OA patients. Flow cytometry showed that the expression of CD13/aminopeptidase N on synovial fibroblasts from RA patients was higher than the expression on synovial fibroblasts from OA patients, and Western blots and RT-PCR showed that synovial fibroblasts from RA patients contained a greater amount of CD13/aminopeptidase N. The activity of CD13/aminopeptidase N correlated significantly with lymphocyte counts in synovial fluids from RA patients. Synovial fluids from RA patients in which high aminopeptidase activity was detected contained considerable chemotactic activity for lymphocytes, and bestatin, a specific inhibitor of aminopeptidases, partially inhibited the chemotactic activity. CONCLUSION: CD13/aminopeptidase N may participate in the mechanism of lymphocyte involvement in inflamed joints of RA patients as a lymphocyte chemoattractant.
15534535 Long-term followup of posterior-cruciate-retaining TKR in patients with rheumatoid arthrit 2004 Nov A consecutive series of 220 primary posterior-cruciate ligament-retaining total knee replacements were done in 148 patients with rheumatoid arthritis. From this group, 212 total knee replacements (141 patients) were followed up for an average of 10 years. Average knee scores at 5, 10, 15, and 20 years after operation improved to 86, 83, 88, and 89, respectively, and average function scores improved to 70, 72, 64, and 88, respectively. Five knees (2.4%) were revised for deep infection. Posterior instability, recurvaum, or mediolateral instability, combined or otherwise, occurred in 15% (32 knees; in 31 patients). Three tibial components (1.4%) were revised: one for suspected aseptic loosening and two for instability. Excluding infections and failed metal-backed patellas, Kaplan-Meier survival rates were 99.5%, 97.9%, and 96.5%, respectively. Favorable long-term results may be achieved with posterior-cruciate ligament-retaining total knee replacements in patients with rheumatoid arthritis. Concern remains, however, about rotational instability in certain cases associated with preoperative genu-valgum and ipsilateral planovalgus deformity.
12847679 Salmonella septicemia in rheumatoid arthritis patients receiving anti-tumor necrosis facto 2003 Jul OBJECTIVE: Patients treated with antibodies to tumor necrosis factor alpha (TNFalpha) have an increased susceptibility to intracellular infections. We describe 2 patients with rheumatoid arthritis (RA) who developed Salmonella septicemia during anti-TNF treatment. The aim of this study was to identify the mechanisms involved in the increased susceptibility of anti-TNF-treated patients to intracellular microorganisms. METHODS: We evaluated an additional 6 RA patients receiving anti-TNF antibodies, 5 RA patients not receiving anti-TNF therapy, and 6 age- and sex-matched healthy volunteers. The in vitro production of cytokines (interleukin-1beta [IL-1beta], IL-6, interferon-gamma [IFNgamma], and IL-10) upon bacterial stimulation of whole blood and the expression of Toll-like receptor 4 (TLR-4) on dendritic cells from RA patients treated with infliximab, RA patients not treated with infliximab, and healthy controls were compared. RESULTS: Stimulation with heat-killed Salmonella typhimurium or Candida albicans led to a significantly decreased production of IFNgamma, but not to a decreased production of IL-10, IL-beta, or IL-6, in anti-TNF-treated RA patients compared with RA patients who were not receiving anti-TNF antibodies and compared with healthy controls. TNF-blocking treatment ex vivo significantly inhibited TLR-4 expression on dendritic cells from RA patients and healthy controls. CONCLUSION: Since recognition of microorganisms by TLR-4 and activation of phagocytes by IFNgamma are essential mechanisms for the defense against intracellular and fungal pathogens, we propose that this pathway is crucial for the increased susceptibility to these microorganisms in patients receiving anti-TNF therapy.
14994405 Lubricating ability of aspirated synovial fluid from emergency department patients with kn 2004 Mar OBJECTIVE: To determine if joint effusions encountered in the emergency department (ED) requiring arthrocentesis possess normal lubricating ability or evidence cartilage degeneration. Chondroprotection of articulating joint surfaces is provided by lubricin, a mucinous glycoprotein that is a product of megakaryocyte-stimulating factor gene (GenBank U70136) expression. Loss of synovial fluid's (SF) lubricating ability has been implicated in the pathogenesis of degenerative joint disease. METHODS: A retrospective ED observational study from May 1, 1999, to October 1, 2000, of adult and pediatric patients presenting with radiographically negative knee joint complaints and clinical evidence of joint effusion. Knee joints were aspirated by the emergency physician and the synovial fluid tested for lubricating ability and collagen type II degeneration. Lubricating ability was assayed in vitro in an arthrotripsometer oscillating latex apposed to polished glass under a load of 0.35 106 N/m2. Results were reported as the coefficient of friction ( micro ) relative to that of a 0.9% NaCl control; negative deltamicro value indicates lubrication. Comparisons of deltamicro were made to normal SF and aspirates from patients with osteoarthritis (OA) and rheumatoid arthritis. Collagen type II fragments were measured by a novel sandwich ELISA. RESULTS: Synovial fluid aliquots (n = 57) lubricated poorly with deltamicro = -0.045 (95% confidence interval = -0.006, -0.083) compared to normal SF with D micro = -0.095 (95% CI = -0.088, -0.101). Only 20.6% of knee joint aspirates possessed normal lubricating ability. An association exists between nucleated cell count and deltamicro described by a logarithmic function. Collagen type II fragments were present in aspirates at a concentration of 0.636 microg/ml (95% CI 0.495-0.777 microg/ml), significantly higher than 0.173 microg/ml (95% CI 0.154-0.193 microg/ml) in the OA comparison group. CONCLUSION: Knee joints with synovitis, commonly encountered in the ED, are frequently nonlubricated bearings and display catabolism of collagen type II. This may play a role in acute cartilage destruction ultimately resulting in posttraumatic OA.