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ID PMID Title PublicationDate abstract
11226477 An improved anti-C3/IgG ELISA for quantification of soluble immune complexes. 2001 Mar 1 A semi-quantitative ELISA for complement-fixing, IgG-containing immune complexes (IC) is described. The assay is based on the insolubilization of IC by polyethyleneglycol, their capture by solid-phase anti-C3 antibodies, reaction with peroxidase-labeled anti-IgG antibodies and incubation with a chromogenic peroxidase substrate. It was markedly improved by the use of a single-step procedure which simultaneously washed and precipitated the insolubilized immune complexes. Intra-assay and inter-assay coefficients of variation were lower than 8.6 and 14.7%, respectively. As expected, higher levels of circulating immune complexes, in relation to healthy individuals, were found in patients with American visceral leishmaniasis (AVL), systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), with prevalences comparable to those described in the literature. The ELISA can be quickly assembled from reagents and plasticware widely available commercially, detects immune complexes fulfilling three different criteria and is more sensitive than a previously published method based on the same principles (detection limit for complement-sensitized aggregated IgG of 2 microg ml(-1) as compared with a detection limit above 16 microg ml(-1)).
11113937 High performance liquid chromatography analysis of D-penicillamine by derivatization with 2000 Dec D-Penicillamine (2-amino-3-mercapto-3-methylbutanoic acid), a well-known heavy metal chelator, is the drug of choice in the treatment of Wilson's disease and is also effective for the treatment of several disorders including rheumatoid arthritis, primary biliary cirrhosis, scleroderma, fibrotic lung diseases and progressive systemic sclerosis. The method proposed incorporates a technique, previously developed in our laboratory, that utilizes the derivatizing agent N-(1-pyrenyl)maleimide (NPM) and reversed-phase high-performance liquid chromatography (HPLC). The coefficients of variation for within-run precision and between-run precision for 500 nM standard D-penicillamine (D-pen) were 2.27% and 2.23%, respectively. Female Sprague-Dawley rats were given 1 g/kg D-pen i.p. and the amounts of D-pen in liver, kidney, brain and plasma were subsequently analyzed. This assay is rapid, sensitive and reproducible for determining D-pen in biological samples.
10618507 The use of flow cytometry to measure neutrophil function. 1999 Dec 17 Neutrophils are important professional phagocytic cells that provide the host with a first line of defense against acute bacterial and fungal diseases and recurrent, severe or unusual infections are associated with inherited defects of neutrophil function. Furthermore, abundant evidence links inappropriate neutrophil-mediated tissue damage to the pathogenesis of conditions such as acute respiratory distress syndrome, septicemia with multiorgan failure, ischemia-reperfusion injury and rheumatoid arthritis. Flow cytometry has been increasingly used to evaluate the functional capabilities of neutrophils. In this review, we discuss the use of flow cytometry to assess neutrophil functional responses including calcium mobilization, F-actin assembly, adhesion, aggregation, degranulation, phagocytosis and reactive oxygen species (ROS) production. The use of flow cytometry to identify neutrophil priming is also discussed. The advantage of flow cytometry is that the majority of neutrophil functions can be measured using a small volume of whole blood that reduces artifactual changes in function caused by purification procedures. The advent of numerous new fluorochromes and multiparametric analysis allows the simultaneous measurement of several neutrophil functions in the same population of cells. Flow cytometric analysis provides a rapid screen for abnormalities of neutrophil function and reflects more accurately their behavior in vivo.
10547158 Increase in circulating levels of monocyte chemoattractant protein-1 with aging. 1999 Oct Monocyte chemoattractant protein-1 (MCP-1) is a member of chemokines with chemoattractant activity for monocytes, T cells, mast cells, and basophils. Precursor mRNA or protein was detected at high levels in the lesions of several diseases, such as pulmonary fibrosis, rheumatoid arthritis, atherosclerosis, and some types of tumors. The regulation of MCP-1 production and the role of this chemokine in pathophysiologic states, however, remain largely unknown. In this study, using an enzyme-linked immunosorbent assay (ELISA), we measured the circulating MCP-1 levels in 405 healthy Japanese subjects of various ages, eliciting a profound age-dependent MCP-1 increase. Multivariate regression analysis revealed that significant predictors of MCP-1 value for males were age (p = 0.033) and serum triglyceride (p = 0.039). For females, age was also a significant predictor (p = 0.00002). One possible explanation is that the plasma MCP-1 concentration might reflect the existence of atherosclerosis, although the plasma MCP-1 concentration from patients with coronary artery disease or cerebrovascular accidents appears not to differ from age-matched, disease-free controls. This is the first report linking an increase in a particular chemokine level with aging.
10468178 Non-steroidal anti-inflammatory drugs with adverse psychiatric reactions: five case report 1999 Adverse drug reactions of non-steroidal anti-inflammatory drugs (NSAIDs) are quite prevalent, but there are few reports about possible adverse psychiatric reactions, which may be ignored or underestimated. We describe here five psychiatric outpatients, two with major depressive disorders, one bipolar disorder, one schizophrenic disorder and one anxiety disorder, who were treated with NSAIDs for pain due to rheumatoid arthritis, osteoarthritis or other painful neuromuscular conditions. All five patients developed a moderate to severe depressive state, three patients became obviously paranoid, and four had either thoughts of suicide or an attempt while undergoing co-administration of NSAIDs. The psychiatric symptoms remitted when the NSAIDs were stopped. The depressive and paranoid symptoms returned on seven occasions of re-use or re-challenge with the same or a different type of NSAID in all five patients. When the NSAIDs were stopped again, the patients had another remission of the adverse psychiatric reactions, and eventually recovered to their baseline mental states in clear temporal relationships. The cases presented suggest that NSAIDs can induce or exacerbate idiosyncratic reproducible adverse psychiatric symptoms in certain vulnerable patients, including those with a variety of psychotic or neurotic disorders, and also in elderly persons, but these undesirable side-effects were generally transient and disappeared on withdrawal of the NSAIDs.
10448597 Serum soluble transferrin receptor and the prediction of marrow aspirate iron results in a 1999 Jun Serum soluble transferrin receptor (sTfR) concentration has been evaluated in the diagnosis of iron deficiency in otherwise healthy individuals and in patients with rheumatoid arthritis, but has not been studied in a general population of patients with complicated clinical presentations. In this study, 145 anaemic patients with a variety of medical conditions undergoing diagnostic bone marrow aspiration for any reason were tested by a complete blood count, a panel of biochemical tests to evaluate iron status, bone-marrow aspirate iron stain, and serum sTfR concentration. Sixteen per cent lacked stainable iron in the marrow aspirate. All biochemical parameters differed significantly between patients with or without stainable marrow iron. The sTfR assay was significantly more sensitive but less specific than other iron status assays in identifying the absence of stainable iron. Logistic regression analysis demonstrated that only sTfR and ferritin contributed independently to the prediction of marrow iron status. Serum ferritin alone was highly specific but insensitive. A decision algorithm combining serum ferritin and sTfR was as sensitive as TfR and as specific as serum ferritin. The measurement of serum sTfR, especially in conjunction with serum ferritin, is a valuable addition to the existing methods for predicting the results of marrow aspirate iron stains.
10380840 The distribution of YKL-40 in osteoarthritic and normal human articular cartilage. 1999 YKL-40, also called human cartilage glycoprotein-39, is a major secretory protein of human chondrocytes in cell culture. YKL-40 mRNA is expressed by cartilage from patients with rheumatoid arthritis, but is not detectable in normal human cartilage. The aim was to investigate the distribution of YKL-40 in osteoarthritic (n=9) and macroscopically normal (n=5) human articular cartilage, collected from 12 pre-selected areas of the femoral head, to discover a potential role for YKL-40 in cartilage remodelling in osteoarthritis. Immunohistochemical analysis showed that YKL-40 staining was found in chondrocytes of osteoarthritic cartilage mainly in the superficial and middle zone of the cartilage rather than the deep zone. There was a tendency for high number of YKL-40 positive chondrocytes in areas of the femoral head with a considerable biomechanical load. The number of chondrocytes with a positive staining for YKL-40 was in general low in normal cartilage. The present findings, together with previous observations, suggests that YKL-40 may be of importance in cartilage remodelling/degradation of osteoarthritic joints.
10340006 [Clinical evaluation of serum cytokine from patients with collagen diseases]. 1999 Apr PURPOSE: Systemic autoimmune diseases such as systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS) are characterized by an imbalance of cytokine production. To clarify the relationship between the profile of cytokines and the pathophysiology of systemic autoimmune diseases, we estimated the cytokine levels in sera from patients with several systemic autoimmune diseases. METHOD: Serum cytokine levels in patients with unclassified connective tissue diseases were measured using ultrasensitive specific enzyme-linked immunosorbent assay (ELISA). RESULT: These patients were diagnosed using the established category by further examinations within a 2-year period. Sera from patients with SLE contained higher titers of IL-10, and equal levels of IFN gamma and TNF alpha compared with those of normal controls. Patients with progressive systemic sclerosis (PSS) showed lower titers of IL-10 and higher titers of IFN gamma and TNF alpha in their sera than those of healthy controls. Seronegative rheumatoid arthritis (snRA) patients had a higher amount of IL-10 and TNF alpha, equivalent level of IFN gamma in their sera compared to those of controls. Moreover, patients with Sjögren's syndrome (SS) showed higher titers of IL-10 and TNF alpha, and an equivalent level of IFN gamma in their sera compared to healthy volunteers. CONCLUSION: Based on these findings, for the differential diagnosis of patients with systemic autoimmune diseases such as SLE, PSS, snRA and SS, it may be useful to measure the levels of cytokines such as IL-10, IFN gamma, and TNF alpha in their sera.
9645922 TNF, apoptosis and autoimmunity: a common thread? 1998 Jun A subset of cytokine mediators belonging to the tumor necrosis factor (TNF) family cause apoptosis, acting through receptors and signaling pathways that have recently come to light. Further, at least one autoimmune disease results from a defined defect of apoptosis (mutations of the Fas ligand or its receptor). It is offered that many, and perhaps most autoimmune diseases may result from primary defects of apoptosis. Such defects may cause reflexive overproduction of TNF and other pro-apoptotic cytokines. The collateral damage produced by these mediators may be of pathogenetic importance in complex autoimmune disorders such as rheumatoid arthritis and Crohn disease, wherein TNF blockade is known to have ameliorative effects.
9553212 [Non-opioid analgesics and co-analgesics in therapy of chronic pain]. 1998 Jan Efficacy and side effects of non-opioid-analgesics were analysed in a standardized review of placebo-controlled or double-blind studies. In rheumatoid arthritis, ibuprofen showed the best ratio of effectiveness and side-effects. Naproxen, diclofenac and meloxicam may serve as alternatives. In osteoarthritis, naproxen seems to be superior to diflunisal, meloxicam and diclofenac. In cancer pain, ibuprofen is the treatment of the first choice followed by naproxen and diclofenac. No sufficient data on non-opioids in neuropathic pain were available. The dose administered in the management of chronic pain should be low in order to reduce the incidence of side-effects. The frequency of side-effect-related discontinuation of chronic pain medication was calculated as follows: ibuprofen 3.8%, aspirin 4.7%, piroxicam 4.8%, naproxen 7.4%, meloxicam 13.0% and diclofenac 17.8%. Since differences in efficacy were not clinically relevant, the indication for a special non-opioid-analgesic medication should focus on the prevention of side-effects.
9531199 The utility of histological examination of tissue removed during elective joint replacemen 1998 Mar The utility of histological examination of tissue removed during elective joint replacement has not been determined. During a one-year period, tissue removed during 168 total joint replacements was submitted for histological examination. The clinical and histological diagnoses, the cost of the histological study, and the clinical course were determined for all joints. Degenerative joint disease, rheumatoid arthritis, and avascular necrosis accounted for 98 per cent of the histological diagnoses. There were sixteen discrepancies between the clinical and histological diagnoses. The histological diagnosis did not affect the treatment of fifteen of these joints. However, the treatment was altered for one joint that had a clinical diagnosis of degenerative joint disease and a histological diagnosis of osteomyelitis; on review, the initial histological diagnosis was determined to be incorrect. In 1996 dollars, the cost of histological examination for all 168 joints was $10,698.24. Although there would be considerable cost-savings on a population basis if histological examination were not performed, this savings must be weighed against the effect of a misdiagnosis on the management of a particular patient.
9334007 [Fractures after total knee joint endoprosthesis. Results of treatment with various stabil 1997 Jun In 20 patients with a fracture of femur or tibia 5.2 years after arthroplasty of knee the results of the operative treatment are presented. The results show that especially bone damaging diseases as rheumatoid arthritis, osteoporosis and the loosening of the endoprosthesis are favorable for the fracture during the follow-up. The conclusion of the investigation shows that in younger patients the external fixation by plates and screws is the preferential treatment, in elderly people or comminuted fracture an internal fixation, also in combination with an additional osteosynthesis, allows a fast mobilization. The number of observed complications is higher than in primary knee arthroplasty, the full weight bearing 1st delayed. The rate of further operations and unsatisfactory results is also higher being affected by the high mean age of the operated patients (73.4 years). The possible use of a total femur implant must be discussed critically because only an individual production can avoid further damage of the parts of the joint that were not concerned by the fracture.
9063239 Amniotic membrane transplantation for persistent epithelial defects with ulceration. 1997 Mar PURPOSE: To determine whether preserved human amniotic membrane can be used as an alternative substrate for treating persistent corneal epithelial defects with sterile ulceration. METHODS: Amniotic membrane transplantation was performed in 11 eyes of 11 consecutive patients with corneal ulcers of different causes that had persisted for a mean +/- SD of 17.5 +/- 13.9 weeks. RESULTS: Ten patients healed in 3.9 +/- 2.3 weeks (P < .01) without recurrence for 9.0 +/- 5.9 months. One patient failed to heal because of preexisting corneal perforation pursuant to severe rheumatoid arthritis. CONCLUSION: Amniotic membrane transplantation may be considered an alternative method for treating persistent epithelial defects and sterile ulceration that are refractory to conventional treatment and before considering treatment by conjunctival flaps or tarsorrhaphy.
9516899 Role of heat shock proteins in the pathogenesis of cystic fibrosis arthritis. 1997 Dec BACKGROUND: Arthritis is a well recognised complication of cystic fibrosis. The cause of this arthritis is not yet clear but it is likely to be an immunological reaction to one of the many bacterial antigens to which the lungs are exposed. One such group, the heat shock proteins, (hsp), was investigated. These are immunodominant antigens of a wide variety of infectious microorganisms and have varying amino acid chain sequences, some of which are similar to those found in human tissues. METHODS: Antibodies to human hsp 27 and hsp 90 in the serum of patients with cystic fibrosis, with and without arthritis, and in normal age and sex matched healthy controls were measured. The severity of the cystic fibrosis was assessed by lung function tests and chest radiographs. The nature of the organisms colonising the lungs was determined by bacteriological examination of sputum. RESULTS: Higher mean titres of serum IgG anti-human hsp 27 and hsp 90 antibodies were found in 50 patients with cystic fibrosis than in healthy controls (hsp 27, 0.25 (95% CI 0.19 to 0.33) versus 0.05 (95% CI 0.04 to 0.07); hsp 90, 0.27 (95% CI 0.22 to 0.32) versus 0.11 (95% CI 0.08 to 0.14)). These antibodies were higher in patients in whom the lungs were colonised with Pseudomonas aeruginosa than in those without infection (hsp 27, 0.41 (95% CI 0.17 to 0.63) versus 0.18 (95% CI 0.10 to 0.27); hsp 90, 0.37 (95% CI 0.18 to 0.57) versus 0.22 (95% CI 0.16 to 0.29)). The eight patients with cystic fibrosis with arthritis had higher anti-hsp 27 antibodies (0.48 (95% CI 0.13 to 0.92)) than the 42 patients without arthritis (0.22 (95% CI 0.17 to 0.30)). CONCLUSIONS: These findings suggest that the arthritis associated with cystic fibrosis, despite being seronegative for rheumatoid factor, was associated with more severe lung disease and with a greater inflammatory response to heat shock proteins.
9355205 Seronegative spondyloarthropathy in familial Mediterranean fever. 1997 Oct To define a possible association between familial Mediterranean fever (FMF) and seronegative spondyloarthropathy (SNSA) and to study features of SNSA in FMF patients, we screened for the presence and manifestations of SNSA in 3,000 FMF patients attending the National Center for FMF in our institution. This population included 160 patients with chronic arthritis, most who suffered from SNSA. Patients were considered to suffer from SNSA if they had chronic arthritis, inflammatory back/neck pain, and sacroiliitis. Patients who had other diseases associated with SNSA were excluded. Eleven patients, nine men and two women, with chronic monoarthritis or oligoarthritis, grade 2 (four patients) or grades 3 to 4 (seven patients), sacroiliitis, and inflammatory back pain met the criteria for diagnosis of SNSA of FMF. These patients were rheumatoid factor (RF) and HLA-B27 negative. In seven patients, spondyloarthropathy developed while they received colchicine, and in four before colchicine. Most patients responded to treatment with nonsteroidal antiinflammatory drugs, but three required second-line agents. These findings suggest that SNSA is one of the musculoskeletal manifestations of FMF that may occur despite colchicine therapy and requires specific treatment.
10229820 Fibroblast growth factor-1 (FGF-1) enhances IL-2 production and nuclear translocation of N 1999 May 15 Fibroblast growth factors (FGFs) are heparin-binding proteins crucial to embryogenesis, angiogenesis, and wound healing. FGF-1 is abundantly expressed in the synovium in rheumatoid arthritis and in rejecting allografts, sites of chronic immune-mediated inflammation. The frequency of FGF-1-responsive T cells is increased in the peripheral blood of these disorders, and a high percentage of infiltrating T cells in rheumatoid arthritis synovium express receptors for FGF-1. To understand the action of FGF-1 in T cells, studies were initiated in Jurkat T cells that express the signaling isoform of FGF receptor-1. These experiments show that FGF-1 stimulation of Jurkat T cells provides a second signal that augments TCR-mediated IL-2 production. Analogous to costimulation via CD28, this activity is mediated through activation of Rel/kappaB, a family of transcription factors known to regulate IL-2 and other activation-inducible proteins. FGF-1 alone induces modest nuclear translocation of kappaB-binding proteins, and this translocation is enhanced by the combination of anti-CD3 and FGF-1. This NF-kappaB binding complex is composed of transcriptionally active p65(RelA)/p50 heterodimers and results primarily from the targeted degradation of IkappaB-alpha, an inhibitor that sequesters Rel/kappaB in the cytoplasm. These data are the first to show a connection between FGF-1 signaling and NF-kappaB activation outside of embryonic development. The signaling events that link FGF receptor-1 engagement and NF-kappaB activation in Jurkat are probably distinct from the CD28 costimulation pathway, since FGF-1-induced Rel/kappaB binding proteins do not contain significant levels of c-Rel and are not identical with the CD28 response complex.
10460188 Double blind glucocorticoid controlled trial of samarium-153 particulate hydroxyapatite ra 1999 Sep BACKGROUND: Samarium-153 particulate hydroxyapatite (Sm-153 PHYP) is a relatively new radiation synovectomy agent developed for the treatment of chronic synovitis. Although it has been shown that the levels of unwanted extra-articular radiation are lower after intra-articular injection of Sm-153 PHYP than yttrium-90 colloid, its clinical efficacy has not been rigorously studied. OBJECTIVES: To establish whether Sm-153 PHYP radiation synovectomy results in a clinically useful benefit sustained at one year. METHODS: In a randomised double blind study, patients received either intra-articular 40 mg triamcinolone hexacetonide alone or 40 mg triamcinolone hexacetonide combined with Sm-153 PHYP in an outpatient clinic. RESULTS: Sixty patients (28 male, 32 female), median age 51 (18-75) with chronic knee synovitis were studied. Diagnoses included: rheumatoid arthritis (n=29); psoriatic arthritis (n=9); ankylosing spondylitis (n=3); reactive arthritis (n=2); undifferentiated seronegative oligoarthritis (n=13) and miscellaneous inflammatory conditions (n=4). More patients who received Sm-153 PHYP/triamcinolone hexacetonide sustained clinical benefit a year after treatment compared with patients who received corticosteroid alone (12 of 31 (39%) v 6 of 29 (21%), a difference of 18% more patients (95% CI -5% to 41%)) though the difference was not significant (chi(2)=2.31, 0.2>p>0.1, n=60). Despite the variation in injected activity (median 563 MBq, range 218-840 MBq), there was no obvious relation between low levels of injected activity (<555 MBq) and relapse within 12 months of treatment (chi(2) =2.61, 0.2>p>0.1, n=31). CONCLUSIONS: There was no clear beneficial clinical effect of combined Sm-153 PHYP/triamcinolone hexacetonide injection over triamcinolone hexacetonide alone a year after treatment for chronic knee synovitis.
8995937 Association of esophagitis and esophageal strictures with diseases treated with nonsteroid 1997 Jan BACKGROUND: It has been speculated that intake of nonsteroidal anti-inflammatory drugs (NSAIDs) represents a risk factor for the occurrence of esophagitis and esophageal strictures. METHODS: A case-control study was conducted to compare the occurrence of comorbid diseases treated with NSAIDs in case and control subjects with and without esophageal disease, respectively. The case population was comprised of all patients with esophagitis (International Classification of Diseases code 530.1) or esophageal stricture (code 530.3) who were discharged from hospitals of the Department of Veteran Affairs between 1981 and 1994. In separate multivariate logistic regressions, the occurrence of esophagitis or esophageal stricture served as the outcome variable, and age, gender, ethnicity, and comorbid occurrence of an NSAID-related diagnosis served as modifier variables. RESULTS: A total of 101,366 individual case subjects were included, of whom 92,860 presented with esophagitis and 14,201 with stricture. The occurrence of erosive esophagitis was associated with osteoarthritis (odds ratio = 1.42, 95% confidence interval = 1.36-1.48), osteoporosis (1.38, 1.25-1.52), back pain (1.49, 1.42-1.56), femur bone fracture (1.46, 0.92-2.32), fibrositis (1.57, 1.41-1.75), tension headache (1.34, 1.27-1.40), ankylosing spondylitis (1.33, 1.24-1.42), rheumatoid arthritis (1.13, 1.05-1.21), sicca syndrome (1.15, 1.05-1.26), and systemic sclerosis (6.16, 4.65-8.14). NSAID-related diagnoses represented similar risk factors for both esophagitis and esophageal stricture. CONCLUSIONS: A large variety of diseases treated by NSAIDs are associated with a significantly increased risk of esophageal erosion or stricture; the risk appears similar for both of these. In some comorbid conditions, the underlying disease process may contribute to the occurrence of esophageal pathology.
10943882 Thrombosis in patients with connective tissue diseases treated with specific cyclooxygenas 2000 Aug Specific inhibitors of cyclooxygenase 2 (COX-2) have been approved for the treatment of osteoarthritis and rheumatoid arthritis. Unlike nonsteroidal anti-inflammatory drugs, specific COX-2 inhibitors do not inhibit platelet activation. However, these agents significantly reduce systemic production of prostacyclin. As a result, theoretical concerns have been raised that specific COX-2 inhibitors could shift the hemostatic balance toward a prothrombotic state. Patients with connective tissue diseases (CTD), who may be predisposed to vasculopathy and thrombosis, often have arthritis or pain syndromes requiring treatment with antiinflammatory agents. Herein we describe 4 patients with CTD who developed ischemic complications after receiving celecoxib. All patients had a history of Raynaud's phenomenon, as well as elevated anticardiolipin antibodies, lupus anticoagulant, or a history compatible with antiphospholipid syndrome. It was possible to measure a urinary metabolite of thromboxane A2 in 2 of the patients as an indicator of in vivo platelet activation, and this was markedly elevated in both. In addition, the patients had evidence of ongoing inflammation as indicated by elevated erythrocyte sedimentation rate, hypocomplementemia, and/or elevated levels of anti-DNA antibodies. The findings in these 4 patients suggest that COX-2 inhibitor-treated patients with diseases that predispose to thrombosis should be monitored carefully for this complication.
10606981 Placenta growth factor (PlGF) induces vascular endothelial growth factor (VEGF) secretion 2000 Jan The aims of this study were (i) to determine whether PlGF, VEGF and PlGF/VEGF heterodimers are detected in synovial fluid (SF) and plasma samples from patients with a range of arthropathies; (ii) to describe whether any correlation exists between SF PlGF, VEGF and PlGF/VEGF heterodimer levels and the total and differential SF leucocyte counts; and (iii) to investigate the regulation of peripheral blood mononuclear cell (PBMC) VEGF secretion by stimuli relevant to inflammatory joints. PlGF, VEGF and PlGF/VEGF heterodimer levels were measured in the SF and plasma of patients with a range of arthropathies and normal controls by ELISA. Western blotting for PlGF was performed on SF from three patients with rheumatoid arthritis (RA) and primary inflammatory arthropathies. VEGF was quantified in cell culture supernatants after stimulation with lipopolysaccharide (LPS), PlGF or cobalt ions of PBMC isolated from RA patients and controls. PlGF and VEGF were detected in all SF samples. PlGF/VEGF heterodimers were detected in 10.2% of SF samples, most frequently in RA samples. Western blotting confirmed the presence of PlGF in RA SF. PlGF was detected in 52% of RA and 31% of control plasma samples, and VEGF was detected in 38% of RA and 38% of control plasma samples. PlGF/VEGF heterodimers were detected in 21% of RA samples and none of the control samples. In primary inflammatory arthropathy patients, SF PlGF and VEGF levels correlated significantly with the SF total leucocyte count and the neutrophil count. PlGF was the most potent inducer of PBMC VEGF production in both RA and control subjects. This is the first report of the detection of PlGF and PlGF/VEGF heterodimers in the SF of patients with inflammatory arthropathies, and we have shown for the first time that PlGF up-regulates PBMC VEGF production. PlGF may therefore play a key role in the production of VEGF in the inflammatory joint.