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ID PMID Title PublicationDate abstract
9237806 Correlation between anti-C1q and immune conglutinin levels, but not between levels of anti 1997 Aug The simultaneous appearance of autoantibodies with either a functional or structural relationship to anti-C1q antibodies (anti-C1q) was investigated in 39 systemic lupus erythematosus (SLE) patients and in 28 rheumatoid arthritis (RA) patients, in both cross-sectional and longitudinal design. Levels of anti-C1q showed an isotype-specific correlation to levels of immune con-glutinin (IK) in SLE patients, whereas no correlation was evident to levels of antibodies to the structurally related antigen type II collagen (anti-CII) in SLE or RA patients. IgG anti-C1q levels correlated with serum levels of the terminal complement complex (sC5b-9) in SLE patients. In two longi-tudinally followed patients, the IK response preceded the anti-C1q response. Possibilities for regulation of the humoral anti-complement response are discussed.
9776116 Comparative study of tetranectin levels in serum and synovial fluid of patients with rheum 1998 Tetranectin (TN) was assessed in paired synovial fluid (SF) and serum (S) samples from 27 patients with rheumatoid arthritis (RA), 23 with seronegative spondylarthritis (SSA) and 22 with osteoarthritis (OA). RA patients had a stronger correlation between serum and SF TN and a higher SF/S TN ratio than did SSA and OA patients. Moreover, the SF/S TN ratio exceeded 1 in most RA patients but not in SSA and OA patients, indicating the possibility of intra-articular TN synthesis in RA. A strong correlation of serum and SF TN with known inflammatory markers was observed in RA. The TN/proteinase inhibitors (PIs: alpha1-antitrypsin, alpha2-macroglobulin) molar ratio in SF was lower in RA and SSA patients to a statistically significant degree than in OA patients. In RA, in contrast to SSA and OA, this ratio correlated positively with the SF interleukin-8 (IL-8), responsible for neutrophil recruitment and degranulation, and negatively with erythrocyte sedimentation rate, serum C-reactive protein and fibrinogen, known markers of disease activity. In conclusion, patients with RA showed lower serum TN levels, a higher SF/S TN ratio and a lower SF TN/PI molar ratio than did SSA and OA patients, suggesting the implication of TN in the impaired regulation of fibrinolysis associated with the inflammatory process.
9150070 Lack of pharmacokinetic interaction of meloxicam with methotrexate in patients with rheuma 1997 May OBJECTIVE: To investigate the pharmacokinetic interaction of oral meloxicam with intravenous (i.v.) methotrexate (MTX) in patients with rheumatoid arthritis (RA). METHODS: Thirteen patients with RA received MTX 15 mg i.v. in the absence of nonsteroidal antiinflammatory drugs (NSAID) and after one week in the presence of steady state levels of meloxicam. Plasma concentrations of MTX and meloxicam were determined using validated high performance liquid chromatography methods. One patient did not complete the study. The interaction of meloxicam and MTX was examined by equivalence testing. The endpoints AUCMTX, VssMTX, CltotMTX, and CmaxMTX were analyzed parametrically, whereas endpoints MRTMTX, CltotMTX, t1/2MTX, and tmaxMTX were analyzed nonparametrically. RESULTS: The MTX plasma concentrations over time, with and without meloxicam, did not differ significantly. The point estimator for the ratio of log transformed data of the primary endpoint AUCMTX was 108%; the lower 95% confidence limit was 100% and the upper 95% confidence limit was 117%. Clinical laboratory values and adverse events revealed no increased MTX toxicity during concomitant treatment with meloxicam. CONCLUSION: In this short term interaction study there was no statistically significantly effect of meloxicam on the pharmacokinetics of MTX. The combination of MTX and meloxicam did not lead to increased MTX toxicity.
11032063 Generalized morphoea in a patient with Felty's syndrome. 2000 May We describe a 54-year-old woman with long-standing rheumatoid arthritis complicated by Felty's syndrome and lung involvement who developed generalized morphoea with no features of systemic sclerosis. To our knowledge this is the first description of such a case.
11174137 Subcorneal pustular dermatosis-type IgA pemphigus induced by thiol drugs. 2001 Jan We report a case of subcorneal pustular dermatosis (SPD)-type IgA pemphigus arising in a 49 year-old woman with rheumatoid arthritis who had been treated with chrysotherapy. Scaly erythemic plaques containing vesicles and pustules occurred on her chest and abdomen during the course of anti-rheumatic treatments using prednisolone at 11 mg/day and thiol compounds (bucillamine and gold sodium thiomalate). Histological investigations revealed subcorneal pustules containing many neutrophils and a few acantholytic cells, and intercellular IgA deposits at the upper epidermis of the eruptions without any other immunoglobulins and complement component C3. Circulating IgA antibodies directed against intercellular spaces of the epidermis were found by prolonged incubation of normal skin specimens in medium containing 20% patient's serum in an explant culture, although standard indirect immunofluorescence for IgA antibodies was negative. The eruptions were treated successfully with prednisolone, 30 mg/day, dapsone, 50 mg/day, and discontinuance of the thiol compound. In addition to the coexistent rheumatoid arthritis, both thiol compounds might have been responsible for the development of the eruptions.
11090038 COX-2 inhibitors. 2000 Oct 16 Cyclooxygenase-2 (COX-2) inhibitors constitute a new group of non-steroidal anti-inflammatory drugs (NSAIDs) which, at recommended doses, block prostaglandin production by cyclooxygenase-2, but not by cyclooxygenase-1. Two COX-2 inhibitors are currently available in Australia--celecoxib, which is taken twice daily, and rofecoxib, which is taken once daily. Both drugs act rapidly in providing pain relief and their anti-inflammatory analgesic effect in osteoarthritis and rheumatoid arthritis is equivalent to standard doses of non-selective NSAIDs. Celecoxib and rofecoxib show significantly lower incidences of gastrotoxicity (as measured by endoscopic studies and gastrointestinal ulcers and bleeds) than non-selective NSAIDs. There is Level 2 evidence that COX-2 inhibitors: reduce pain in classic pain models--third-molar extraction, dysmenorrhoea and after orthopaedic surgery; reduce pain and disability in osteoarthritis of the hip and knee; and reduce pain and disability in rheumatoid arthritis. Other adverse effects, such as interference with antihypertensive agents and the potential to produce renal dysfunction in patients with compromised renal function by COX-2 inhibitors, seem similar to those of non-selective NSAIDs.
9133962 Gliostatin/platelet-derived endothelial cell growth factor as a clinical marker of rheumat 1997 Mar The objective was to assess the congruity of gliostatin/platelet-derived endothelial cell growth factor (GLS PD-ECGF) with other clinical markers of rheumatoid arthritis (RA) and to define its molecular mechanism of action in the complicated cytokine network during RA pathogenesis. Immunoassay systems were used to quantify GLS or cytokine levels in laboratory and clinical samples. Expression levels of GLS were determined by reverse transcription-polymerase chain reaction methods. The GLS levels in synovial fluid were correlated with interleukin-1 (IL-1) and IL-8. The serial data of serum GLS levels reflected well changes in the disease activity during the clinical course of four representative patients with RA. In cultured fibroblast-like synoviocytes, tumour necrosis factor-alpha (TNF-alpha), IL-1, IL-6 and IL-8 induced GLS expression. In conclusion, our results suggest that the serum GLS level, mostly derived from cytokine-stimulated synoviocytes, was a useful clinical marker of RA.
9263140 Effects of low dose methotrexate on the bone mineral density of patients with rheumatoid a 1997 Aug OBJECTIVE: To determine the effects of low dose methotrexate (MTX) on bone mineral density (BMD) of patients with rheumatoid arthritis (RA). METHODS: We examined the relationship between BMD and disease modifying antirheumatic drug (DMARD) use with data from a prospective, randomized, placebo controlled trial assessing the effects of calcium and vitamin D3 supplementation on BMD of patients with RA. Measurements of BMD of the lumbar spine and femoral neck were performed at baseline and at yearly followup visits over 3 years. RESULTS: Information about DMARD use and BMD was available for 133 patients at baseline, and for 95 patients at Year 3. Lumbar spine and femoral neck BMD of MTX and non-MTX treated patients were similar at the start of the study. At the end of 3 years of followup, there was no significant differences in the change in BMD of the femoral neck and lumbar spine in MTX and non-MTX treated patients, in general. However, patients treated with prednisone > or = 5 mg/day plus MTX had greater loss of BMD in the lumbar spine than patients treated with a similar dose of prednisone without MTX (difference -8.08% over 3 years; p = 0.004). CONCLUSION: At the end of 3 years, low dose MTX use was not associated with change in femoral neck or lumbar spine BMD in patients who were not treated with corticosteroids. However, among patients treated with prednisone > or = 5 mg/day, combined treatment with MTX and prednisone was associated with greater bone loss in the lumbar spine than treatment with prednisone without MTX.
11171676 Demonstration of mast cell chemotactic activity in synovial fluid from rheumatoid patients 2001 Mar OBJECTIVES: The significance of the mast cell in the pathogenesis of rheumatic diseases has become more evident. Although mast cell hyperplasia is a feature of rheumatoid arthritis, the nature of mast cell chemoattractants involved in the recruitment of mast cells in joint diseases has not been studied in any detail. In this study the presence of mast cell chemotactic activity in synovial fluids was examined. METHODS: Synovial fluids from seven rheumatoid patients were tested in a modified Boyden chamber, where a human mast cell line was used as responder. The presence of stem cell factor (SCF) and transforming growth factor beta (TGFbeta) was measured by enzyme linked immunosorbent assay (ELISA). RESULTS: Six of the seven synovial fluids tested exhibited mast cell chemotactic activity. Two characterised human mast cell chemotaxins, SCF and TGFbeta, were highly expressed in the synovium. Soluble SCF could be detected in all fluids analysed. Blocking antibodies against SCF or TGFbeta almost completely blocked the activity in one fluid, partially blocked the activity in three, and did not affect the activity in two. Treatment of the responder cells with pertussis toxin reduced the migratory response against seven fluids, indicating the presence of chemoattractants mediating their effect through G(i) coupled receptors. CONCLUSION: These data demonstrate the presence of multiple factors in synovial fluid acting as mast cell chemoattractants, two of which are SCF and TGFbeta that contribute to the effect. These findings may be of importance for developing new strategies to inhibit mast cell accumulation in rheumatic diseases.
9058643 Regulation of interleukin (IL)-1beta gene transcription induced by IL-1beta in rheumatoid 1997 Mar OBJECTIVE: To investigate the process involved in the production of and responsiveness to interleukin 1beta (IL-1beta) in synovial fibroblast-like cells, we analyzed the enhancer region of pro-IL-1beta gene in a cell clone, E11, established from a patient with rheumatoid arthritis (RA). METHODS: A cell clone, E11, was derived from rheumatoid synovial fibroblast-like cells transformed with simian virus 40 large T antigen expression vector by electroporation. Responsiveness of E11 to IL-1beta was analyzed by [3H] thymidine incorporation and Northern blotting. IL-1beta responsive elements on pro-IL-1beta gene were analyzed by chloramphenicol acetyltransferase analysis. RESULTS: E11 resembled synovial fibroblasts based on morphological characteristics and phenotypic analysis. It also demonstrated marked enhancement of proliferation and rapid induction of IL-1beta mRNA expression by IL-1beta. We also identified IL-1beta responsive elements on the pro-IL-1beta gene at a position between -3134 and -3092 that contains the AP-1 binding site and between -2782 and -2729, which includes both AP-1 and nuclear factor-kappaB (NF-kappaB) binding sites. CONCLUSION: AP-1 and NF-kappaB binding elements were required for transcriptional regulation of the IL-1beta gene in the autocrine growth system of RA synovial cells.
9020452 Hydroxyapatite in revision of total hip replacements with massive acetabular defects: 4- t 1997 Jan Hydroxyapatite (HA) granules of 100 to 300 microm, 0.9 to 1.2 mm and 3.0 to 5.0 mm were mixed in a ratio of 10:45:45 and packed into massive bone deficiencies in revision operations for total hip arthroplasty. We did not use additional graft or cup support for deficiencies of the lateral and medial wall. The procedure was carried out in 40 hips between 1986 and 1992. The radiographic spaces seen at the interface between HA and bone immediately after surgery disappeared within three months. Some spaces appeared between HA granules near the bone in the lateral part of two joints, and three sockets migrated in patients with severe segmental and cavitary deficiencies. Direct bonding of HA to bone was observed radiologically without morphological changes, except in the three joints with migration. All patients could walk without pain but the three with definite loosening needed crutches.
11890647 Updated consensus statement on tumour necrosis factor blocking agents for the treatment of 2001 Nov TNF blocking agents have proved to be effective DMARDs and they have been a major advance in the treatment of RA. Their use is expanding to other rheumatic diseases. However, rare to uncommon and unexpected toxicities have been found and others may yet be found during their use. Studies in selected areas of efficacy, toxicity, and general use of TNF blocking agents are needed to help further define the most appropriate use of these agents. Use of these drugs will require doctors experienced in the diagnosis, treatment, and assessment of RA and other rheumatic diseases. These doctors will need to make long term observations of efficacy and toxicity. Further considerations which must be made when using TNF blocking agents in this disease include the cost and a recognition that data in subgroups are still being acquired. It is hoped that this statement, which is based upon the best evidence available at the time of its creation, and modified by expert opinion, will facilitate the optimal use of these agents for our patients with RA and other rheumatic diseases.
9874575 Deletion of fcgamma receptor IIB renders H-2(b) mice susceptible to collagen-induced arthr 1999 Jan 4 Autoimmune diseases, like rheumatoid arthritis, result from a dysregulation of the immune response culminating in hyperactivation of effector cells leading to immune-mediated injury. To maintain an appropriate immune response and prevent the emergence of autoimmune disease, activation signals must be regulated by inhibitory pathways. Biochemical and genetic studies indicate that the type IIB low-affinity receptor for immunoglobulin (Ig)G (FcgammaRIIB) inhibits cellular activation triggered through antibody or immune complexes and may be an important component in preventing the emergence of autoimmunity. To investigate the role of FcgammaRIIB in the development of type II collagen (CII)-induced arthritis (CIA), a model for rheumatoid arthritis in humans, we have examined its contribution in determining the susceptibility to CIA in the nonpermissive H-2(b) haplotype. H-2(b) mice immunized with bovine CII do not develop appreciable disease. In contrast, immunization of the FcgammaRIIB-deficient, H-2(b) mice with bovine CII induced CIA at an incidence of 42.2%. The maximal arthritis index of the FcgammaRIIB-deficient mice developing CIA (6.9 +/- 3.6) was comparable to that of DBA/1 mice (8.6 +/- 1.9), an H-2(q) strain susceptible for CIA induction. IgG1, IgG2a, and IgG2b antibody responses against CII were elevated in the FcgammaRIIB-deficient animals, especially in those mice showing arthritis, but less pronounced than DBA/1 mice. Histological examinations of the arthritic paws from FcgammaRIIB-deficient mice revealed that cartilage was destroyed and bone was focally eroded in association with marked lymphocyte and monocyte/macrophage infiltration, very similar to the pathologic findings observed in DBA/1 mice. These results indicate that a nonpermissive H-2(b) haplotype can be rendered permissive to CIA induction through deletion of FcgammaRIIB, suggesting that FcgammaRIIB plays a critical role in suppressing the induction of CIA.
10406409 Insufficiency fractures of the tibia and fibula. 1999 Jun OBJECTIVE: Insufficiency fractures (IF) occur when normal or physiological muscular activity stresses a bone that is deficient in mineral or elastic resistance. IF of the tibia and fibula are probably less common than IF of the ribs, vertebrae, hip, pelvis, and distal ulna, and therefore they are frequently underrecognized and mistaken for other conditions. Our aim was to analyze the main features and outcome of IF of the tibia and fibula in patients attending our Rheumatology Service. METHODS: IF was considered when occurring spontaneously or with minimal trauma. Between January 1984 and July 1997, 25 patients were diagnosed as having IF of the tibia and fibula. The main predisposing factors, clinical features, therapy, and outcome were retrospectively reviewed. RESULTS: All the patients except four were women (mean age, 66+/-12 years). Three cases were diagnosed between 1984 and 1990 (0.42 cases/year) and 22 between 1991 and 1997 (three cases/year). Eighteen patients had an underlying condition: rheumatoid arthritis (RA, 13 cases), psoriatic arthritis (2), systemic lupus erythematosus (SLE) (1), kidney transplant (1), and Crohn's disease (1). Eleven patients had osteoporotic fractures in other locations. Risk factors for osteoporosis were corticosteroids (13 cases), prolonged immobilization (10), early menopause (2), and methotrexate therapy (10). All patients had pain on weight bearing and marked functional impairment, 16 had local inflammatory signs, and 10 had deformity. In only five patients the diagnosis of IF was considered at the first examination. The diagnostic delay was 76+/-117 days (median, 21). The initial radiograph was diagnostic in 20 patients, and in the remaining the diagnosis was made by computed tomography (CT) scan (three cases), magnetic resonance imaging (MRI) (1), and bone scan (1). IF were located as follows: tibia (10 cases), fibula (seven), tibia and fibula (eight). Nineteen patients were treated with conservative management, four received no specific treatment, and two required surgery. Sixteen patients were hospitalized for a mean period of 12+/-8 days. Most patients had complete recovery. The high frequency of IF seen in RA patients is probably due to the severe disease in patients treated by our Service and that such patients have a higher risk for osteoporosis and its complications. CONCLUSIONS: IF of the tibia and fibula are probably more common than previously thought. They usually occur in patients with underlying rheumatic diseases, mainly RA, and are frequently mistaken for other joint and bone conditions. Despite a frequent delay in diagnosis, they have a good prognosis with conservative management. Nonetheless, a higher index of suspicion may avoid unnecessary investigations and treatments.
11145721 Anti-CD69 autoantibodies cross-react with low density lipoprotein receptor-related protein 2001 Jan 15 We investigated whether autoantibodies to CD69, one of the earliest markers of lymphocyte activation, exist in the sera of patients with systemic autoimmune disease. Serum samples were obtained from patients with rheumatoid arthritis (RA), systemic lupus erythematosus, and Behcet's disease, and were tested for the presence of anti-CD69 autoantibodies by ELISA and Western blotting using rCD69 fusion proteins. IgG-type autoantibodies to CD69 were detected in the sera of 38.3% of the RA patients, 14.5% of the systemic lupus erythematosus patients, and 4.0% of the patients with Behcet's disease. Among those with RA, the anti-CD69 autoantibody-positive patients had a higher serum level of rheumatoid factors and a more accelerated erythrocyte sedimentation rate than the anti-CD69 autoantibody-negative patients. Further, the predominant epitope on the CD69 molecule to which most of the anti-CD69 autoantibody-positive serum samples exclusively reacted, was mapped at the C terminus of CD69. Of interest, this epitope is homologous to a stretch of amino acids in the protein sequence of low-density lipoprotein receptor-related protein 2 (LRP2), which is a receptor for multiple ligands including beta-very low density lipoprotein and is also an autoantigen responsible for Heymann nephritis in rats. The anti-CD69 autoantibody cross-reacted to LRP2 through the homologous amino acid sequence. To our knowledge, this is the first evidence of the existence of anti-CD69 autoantibodies. This autoantibody may modulate the function of CD69- and LRP2-expressing cells.
10325664 Cyclosporin A therapy in rheumatoid arthritis: only strict application of the guidelines f 1999 Mar OBJECTIVES: To investigate (1) whether the increase in serum creatinine observed during cyclosporin A (CsA) therapy was reversible in a group of patients with rheumatoid arthritis (RA) treated before the current guidelines for safe use in RA were developed and (2) whether the application of these guidelines prevents serum creatinine increases in the long term. PATIENTS AND METHODS: Eighty-three RA patients who had started low-dose CsA therapy between September 1990 and October 1992, and who were treated according to guidelines that allowed a 50% rise in serum creatinine, were tested for serum creatinine levels in December 1995 if they had discontinued CsA for at least 3 months. Predictors for irreversibility of renal function were determined by using multiple regression analysis. RESULTS: The mean level of serum creatinine gradually increased from 69+/-14 (mean+/-S.D.) micromol/l when starting CsA therapy to 88+/-23 micromol/l (28% above baseline) at the moment of CsA discontinuation, and had decreased to 80+/-17 micromol/l (16% above baseline) at follow-up, 35+/-14 months after drug discontinuation. During CsA therapy, the mean level of serum creatinine had increased to 82+/-19 micromol/l (26% above baseline) at 6 months and to 87+/-22 micromol/1 (39% above baseline) at 42 months. The mean CsA dose had decreased from 3.1+/-0.9 mg/kg/day at 6 months to 1.9+/-0.8 mg/kg/day at 42 months. The absolute number of months that serum creatinine levels were > 30% above baseline was an independent predictor for a persistent increase of the serum creatinine after CsA discontinuation. More than 2 months with a serum creatinine increase of > or = 30% resulted in a higher percentage irreversible increase than for less than 2 months with a > or = 30% increase: 27 and 6%, respectively (P < 0.0001). CONCLUSION: Long-term low-dose CsA administration in RA patients was associated with an increase in serum creatinine which was partially irreversible after drug discontinuation. The increase in serum creatinine was completely reversible in the patient group that was treated according to the current guidelines for safe use of CsA.
11797119 Unusual morphology in a case of large granular cell leukemia. 2001 Dec Large granular lymphocyte proliferative status represents a group of clonal and nonclonal lymphoproliferative disorders of natural killer (NK) or T-cell lineages with common morphological features. Cellular differences may sustain the clinical polymorphism observed in these disorders. Here we report a case of large granular lymphocyte disease unusually expressing CD4+CD8+ clonal T cells and atypical cell morphology in bone marrow.
9681390 The tumour necrosis factor family of receptors/ligands in the serum of patients with rheum 1998 Jun We investigated the serum concentration of the tumour necrosis factor (TNF) family ligands (TNF-alpha and TNF-beta) and their soluble receptors (sTNF-R p55 and sTNF-R p75) in 66 patients with rheumatoid arthritis (RA) and 14 healthy subjects as a control group, using an enzyme-linked immunosorbent assay (ELISA). We examined a possible association between the serum levels of these proteins and RA activity according to the Mallya & Mace scoring system and Ritchie's index. We also evaluated the correlation between the serum levels of ligands and their soluble receptors as well as the ligands and receptors concentration and the duration of the disease. TNF-alpha, sTNF-R p55 and sTNF-R p75 were detectable in the serum of all 66 patients and 14 healthy individuals. In contrast, TNF-beta was measurable in only 14(21.9%) patients with RA and in none of the control subjects. The highest TNF-alpha, sTNF-R p55 and sTNF-R p75 levels were found in those patients in stage 4 of the disease, and the lowest in the control group. We found a positive correlation between sTNF-R p55 and sTNF-R p75 concentrations and Ritchie's index and no correlation with TNF-alpha and TNF-beta. TNF-alpha, sTNF-R p55 and sTNF-R p75 serum levels correlated positively with the duration of the disease, but levels of TNF-beta did not. We observed a positive correlation between the concentrations of TNF-alpha with sTNF-R p55 and with sTNF-R p75, as well as between both soluble receptors. In contrast, we have not observed any correlation between the serum level of TNF-beta with TNF-alpha, sTNF-R p55, and sTNF-R p75. Our studies indicate that TNF-alpha, sTNF-R p55 and sTNF-R p75, but not TNF-beta (lymphotoxin alpha) are good markers of RA activity and that these proteins play an important role in the pathogenesis of this disease.
9890486 The utility of bone scans in rheumatology. 1999 Jan PURPOSE: Bone scanning is the most common diagnostic imaging service requested by Australian rheumatologists, who order $50,000 (Australian) worth of bone scans annually. METHODS: To determine why rheumatologists request bone scans and how they affect their patient management, the authors administered a two-part prospective survey before and after every bone scan ordered by four rheumatologists during a 6-month period in 1996. RESULTS: A total of 136 bone scans were requested. The primary indications for scanning were to confirm a clinical diagnosis (38%), to exclude a diagnosis (34%), and to localize the site of pain (17%). The common diseases that rheumatologists were attempting to confirm or exclude with bone scanning were inflammatory arthritis, malignancy, and fracture. However, the most common provisional and final diagnosis was soft tissue rheumatism (18%), followed by inflammatory arthritis (15%) and osteoarthritis (11%). Bone scans were successful in excluding a diagnosis in 87% and confirming a diagnosis in 80%. In 32%, bone scans altered the clinical diagnosis, and in 43% they changed the course of disease management. Bone scan results prevented further investigations in 60%.
10513800 Serum levels of hyaluronan, antigenic keratan sulfate, matrix metalloproteinase 3, and tis 1999 Sep OBJECTIVE: To evaluate whether and how moderate physical activity following a night of rest influences serum levels of matrix metalloproteinase 3 (MMP-3), tissue inhibitor of metalloproteinases 1 (TIMP-1), antigenic keratan sulfate (Ag KS), and hyaluronan (HA) in 10 normal subjects and 38 patients with rheumatoid arthritis (RA). METHODS: Blood was obtained from 20 RA patients before they arose from a night's sleep, and again 1 and 4 hours after they had begun to perform moderate physical activity. Another 18 RA patients remained in bed and blood was sampled at the same time periods. Serum levels of MMP-3, TIMP-1, Ag KS, and HA were measured by enzyme-linked immunosorbent assay. Clinical activity was evaluated by the Lansbury index. RESULTS: Both in normal subjects and in RA patients who did not remain in bed throughout the period of blood sampling, levels of HA, Ag KS, and MMP-3 increased significantly during the first hour after the subjects arose: the increase in HA and Ag KS correlated with the Lansbury index in the RA group. Three hours later, levels of Ag KS had dropped to baseline values in both groups of subjects. Levels of HA remained significantly and moderately elevated in the RA group but not in the control group, while levels of MMP-3 did not drop significantly in either group. In contrast, levels of HA, Ag KS, and MMP-3 did not change significantly in RA patients who had remained in bed. Unlike the other markers, the levels of TIMP-1 remained unchanged at the different time periods in all 3 groups studied. CONCLUSION: Significant changes in serum levels of some metabolic markers occur during the first hour after one arises from a night of sleep, especially in patients with RA. Measurement of the magnitude of these changes at different times in individual patients provides very different information about metabolic changes occurring in joint tissue than does measurement of the level of the markers at a single time point, as is usually currently reported.