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ID PMID Title PublicationDate abstract
10604236 Genetic basis for rheumatoid arthritis. 1999 Rheumatoid arthritis (RA) is a common disabling disorder of unknown etiology. In the past 2 decades, a number of studies have examined the genetic basis for RA. One major focus of these studies has been to identify genes within the MHC class II (HLA-DR) chromosomal region, which confer susceptibility/resistance to RA. A strong association between HLA-DR4 and adult seropositive RA has been observed in majority of populations. In addition, there is evidence of a positive association between HLA-DR1 and RA. On the basis of prevalence of DR1 (B1*0101) and of subtypes of DR4 (B1*0401, B1*0404 and B1*0405), it has been suggested that a five amino acid sequence motif (QKRAA/QRRAA) from position 70 to 74 in the third hypervariable region of DRbeta1 molecules is associated with susceptibility to RA. These associations between RA and HLA-DR genes are however incomplete in that about 1/4 of patients do not carry RA-susceptibility DRB1 epitope. Since MHC class III region contains genes that are involved in immune response, we have recently examined the role of a number of microsatellites (D6S273, Bat2, TNFa) and HSP70 promoter region alleles in susceptibility to RA. The results demonstrate that two regions in MHC, class II (DRbeta1) and class III (D6S273, HSP70, Bat2, TNFa) more completely define the risk for development of RA.
11169523 Apoptosis in rheumatoid arthritis--expression of Fas, Fas-L, p53, and Bcl-2 in rheumatoid 2001 Jan Recent studies have suggested that apoptosis is one of the pathogenetic mechanisms in rheumatoid arthritis (RA). In this study, by using single and double immunohistochemical staining assays, Fas, Fas-L, p53, and Bcl-2 were measured simultaneously in RA and osteoarthritic (OA) and post-traumatic (PT) synovial tissues (ST) in order to understand the distribution of these apoptosis-related proteins. The TdT-mediated dUTP-biotin nick end labelling (TUNEL) method was performed to detect apoptotic cells. There was a significant increase of Fas, Fas-L, and p53 in RA ST, compared with OA or PT, but no significant difference of Bcl-2 expression was detected between patient groups. In RA ST, expression of Fas and p53 was detected in sub-lining layers and the majority of Fas- and p53-expressing cells were fibroblast-like synoviocytes. A positive correlation between Fas and p53 was demonstrated in RA ST. In RA ST, one-third of Fas-positive and 80% of p53-positive cells were also TUNEL-positive. These results indicate that apoptosis in RA is strongly associated with the expression of Fas and p53, but not Bcl-2.
11642646 Resolved: Low-dose prednisone is indicated as a standard treatment in patients with rheuma 2001 Oct It is known and has been repeatedly demonstrated that low doses of prednisone or prednisolone (10 mg daily or 5 mg bid) will control most of the inflammatory features of early polyarticular rheumatoid arthritis (Table 2). Also, low doses of prednisolone are known to retard the bony damage of rheumatoid arthritis, and thus these are the original disease-modifying antirheumatic drugs. Glucocorticoids are potent antiinflammatory and immunosuppressive agents by virtue of their repression of the genomic expression by transcriptional interference, inhibiting such proinflammatory proteins as COX-2, IL-1, IL-2, IL-6, TNFalpha, and adhesion molecules. Nature has produced an ideal antiinflammatory and immunosuppressive agent, namely glucocorticoids, and it is up to us to use it in appropriate situations (e.g., active early inflammatory polyarticular rheumatoid arthritis) and in low doses, frequently daily divided doses. Low doses of glucocorticoids (prednisone or prednisolone) accomplish everything NSAIDs or COX-2 inhibitors accomplish but with more antiinflammatory effects, fewer side effects, and much less expense. It is certainly possible (but not precisely tested) that low doses of prednisone (prednisolone) enhance the effects of other DMARDs, including anti-TNF agents. The side effects of low-dose glucocorticoids are minimal. By using concomitant calcium and vitamin D and monitoring bone status with DEXA scans, the osteopenia potential of low doses of prednisone will be minimal. The use of low-dose prednisone without NSAIDs will put the patient at very little risk for stomach ulceration and bleeding.
9340952 [Combination therapy with remission-inducing drugs in chronic polyarthritis: 1996 update]. 1997 May Therapy of rheumatoid arthritis with a combination of several disease-modifying drugs aims to better control of the disease than achievable by monotherapy. Subsequent to a paper written two years ago, this publication reviews studies dealing with combination therapy issued mainly in 1995 and 1996. Most studies deal with MTX as one of the partners. Beneficial results were reported for the combination of methotrexate with antimalarials, cyclosporine or sulfasalazine. The triple combination of methotrexate with hydroxychloroquine and azathioprine is especially promising although the studies presented up to now are still insufficient for its final assessment, due to methodologic problems. Similarly, the value of the combination of sulfasalazine with injectable gold, of sulfasalazine with methotrexate and hydroxychloroquine, or of methotrexate with injectable gold is still uncertain.
11057107 [Pseudochylothorax during the course of rheumatoid arthritis]. 1999 Psudochylothorax is uncommon among pleural fluids. It can be observed during tuberculosis or rheumatoid arthritis in majority. A case of a 62 years old man with chronic pleural fluid is presented. Patient had rheumatoid arthritis diagnosed 40 years ago. For last 13 years symptomsless bilateral pleural fluid was observed. Antituberculous drugs were used without success. Plural fluid obtained after puncture had high level of cholesterol with it[symbol: see text]s crystals, without chylomikrons and triglycerides. Diagnosis of pseudochylothorax in the course of rheumatoid arthritis was established. After plural puncture fluid was removed and did not appear later. Differential diagnosis of pleural fluids is presented.
9235814 [Therapeutic approaches of general practitioners and rheumatologists in South Germany in r 1997 Mar Using "paper patients" we compared the therapeutic approaches of general practitioners and rheumatologists to rheumatoid arthritis and to osteoarthritis of the knee. The mailed survey contained a mild, a moderate and a severe case of rheumatoid arthritis (RA) and a case of osteoarthritis (OA) of the knee. 111 out of 252 general practitioners and 78 out of 132 rheumatologists selected at random participated in the study. We found that rheumatologists would choose more non-steroidal anti-inflammatory drugs (NSAID), disease modifying antirheumatic drugs (DMARD), steroids and physical therapy. In case 4 (OA of the knee) rheumatologists would more frequently recommend analgesics, local steroids, occupational therapy, surgery and ortheses. Primary care physicians on the other hand prescribed more chondroprotective agents. Patients with RA and OA of the knee would be treated differently by primary care physicians and rheumatologists. In order to develop a more uniform therapeutical concept and therefore to reach a better management of the rheumatic patient, a close co-operation of the two physician groups is needed.
10565260 Correlation of hand bone mineral density with the metacarpal cortical index and carpo:meta 1999 Oct This study proposed an assessment of the correlation of hand bone mineral density measured by dual energy x-ray absorbtiometry (DXA) with the carpo:metacarpal (C:MC) ratio and metacarpal cortical index (CI) in patients with rheumatoid arthritis (RA). The correlation of total hand BMD, CI and C:MC ratio with BMD at other sites, the Health Assessment Questionnaire (HAQ) and Larsen scores were also examined. The hand and axial BMD of 30 female patients were also compared with 29 age-matched healthy female controls. Total hand BMD values of patients were significantly lower than the control group. There was no significant difference between groups in axial measurements. CI correlated moderately with the second metacap (II.MC) midshaft and total hand BMD. The C:MC ratio correlated with II.MC midshaft and total hand BMD. Total hand BMD correlated moderately with the AP spine (L2-L4) and femoral neck BMD. Larsen scores showed weak negative correlation with II.MC midshaft BMD and CI. Grip strength correlated weakly only with total hand BMD. The results indicated that CI may reflect cortical bone mass of the hand accurately and did not predict bone density of the spine or hip in patients with RA. The C:MC ratio is a useful method for evaluating progression of wrist involvement and may be related to the loss of hand bone mineral density associated with disease process.
10068009 Survivorship and radiological analysis of the standard Souter-Strathclyde total elbow arth 1999 Jan We undertook a radiological analysis of 186 standard Souter implants to determine survivorship and to analyse the pattern of failure in those needing revision. The implants had been inserted as a primary procedure in patients with rheumatoid arthritis of the elbow at our hospital over the last 12 years. Taking revision as an endpoint, the survivorship after 12 years was 87%. If, however, revision and loosening, defined as the Hindex value equivalent to demarcation of 1 mm around the whole implant, are also included, the survivorship falls to 80%. Of the 24 implants revised, 18 (75%) were for problems with the humeral component, three (12.5%) with the ulnar component and three (12.5%) for instability. Loosening of the humeral component occurred when the implant extended into the humerus, with the tip moving anteriorly on to the anterior humeral cortex. Our study indicates that loosening can be predicted by the rate of change in this angle of extension of the prosthesis.
9175024 Methotrexate use in systemic lupus erythematosus. 1997 Low dose pulse oral methotrexate (MTX) is a well established treatment for rheumatoid arthritis, and short term open studies have suggested beneficial effects of MTX in SLE. This study was designed to investigate MTX treatment maintenance rates in SLE using life table analysis, and to determine whether MTX use was associated with a dose reduction of concomitant steroid therapy. All SLE patients managed by physicians affiliated with a single centre were studied cross-sectionally. Information regarding disease variables and drug use were ascertained by interview and chart review. Drug therapy data including dates of treatment and indications for treatment were analysed using Kaplan-Keier life table methods. Among 101 subjects with SLE, 25 MTX treatment episodes were observed in 24 subjects. The period studied totalled 19766 patient-days, with a median (range) duration of observed MTX treatment of 14.4 (5.1-41.6) months. The median (range) initial and peak MTX doses with 7.5 (2.5-10)mg/wk and 10 (7.5-15) mg/week respectively. The principal indication for commencing methotrexate therapy was arthritis. Only two subjects terminated treatment for toxicity, with the most common reason for termination being remission. The cumulative probability of continuing treatment was 68% at 12 months and 61% at 24 months, or 75% and 71% respectively if cessations for remission were excluded. The median (interquartile range) monthly steroid intake during MTX therapy [279.4 (193.4-492.9)mg] was somewhat lower than during the 6 months prior to [298.1 (237.9-531.4)428.8)mg] MTX therapy, but this difference was not significant. A total of 36% of subjects reduced their steroid dose during MTX therapy, but this reduction was not significant. Treatment of SLE with MTX, predominantly for arthritis, was well tolerated over prolonged periods of observation. Toxicity of sufficient severity to lead to treatment termination was uncommon. A subset of subjects were able to reduce steroid intake during MTX therapy, but no overall reduction in steroid dose was observed.
11094620 [Autoantibodies, diagnostic and prognostic markers of rheumatoid polyarthritis]. 2000 Oct 21 AN IMPORTANT CLINICAL TOOL: A sensitive and specific marker allowing the diagnosis of rheumatoid arthritis, and even more importantly an early assessment of severity, would be a highly valuable clinical tool. Autoantibodies have been found to be quite useful in clinical practice for diagnosis and assessing prognosis. EARLY-STAGE RHEUMATOID ARTHRITIS: Ideally, the marker should be sensitive and specific when the first signs of the disease develop. To date, only the rheumatoid factor and anti-filaggrin antibodies (including anti-stratum comeum or "anti-keratin" and anti-perinuclear factors) have been used with sufficiently acceptable standards. IgM rheumatoid factors can be detected in about 80% of patients with rheumatoid arthritis but they lack specificity since they are also found in other auto-immune conditions (lupus, Sjögren's syndrome), in chronic infections, and in certain lymphoproliferative syndromes (with or without cryoglobulinemia). Anti-filaggrin antibodies are more specific (70 to 100% depending on the study) but can only be detected in 30 to 50% of the patients. High titers of rheumatoid factors (IgM and/or IgA) and anti-filiggrin antibodies are factors of poor prognosis because they are associated with destructive polyarthritis, sometimes complicated with extra-articular signs (nodules, vasculitis). Among the new autoantibodies being studied, only anti-Sa appears to have real diagnostic and prognostic value. The recent data must be confirmed. STRATEGIES FOR OVERT DISEASE: Systematic and repeated assay of autoantibody levels is not warranted in patients with overt disease. Anti-Ro-SS/A, ANCA can however, in some cases, detect unusual complications. THREE STRATEGIES WOULD BE PARTICULARLY INTERESTING: The first is to search for highly specific markers with the aim of identifying a subgroup of rheumatoid arthritis patients as early as possible who have specifically defined clinical, biological and disease-progression criteria. The second is to validate composite scores integrating autoantibodies to achieve early definition of disease severity. The third is to search for markers of progression, particularly autoantibodies, that could modulate inflammatory processes and osteo-cartilaginous degeneration.
9496152 Differential expression and functional behaviour of the alpha v and beta 3 integrin subuni 1997 Dec OBJECTIVE: The aim of this study was to investigate in situ the expression of the classic vitronectin (VN) receptor consisting of the alpha v and beta 3 subunits in synovial lining cells (SLC) of chronic synovitis occurring in osteoarthritis (OA) and in rheumatoid arthritis (RA). The expression and function of alpha v and beta 3 as VN receptor in cultured fibroblast-like synoviocytes (FBS) derived from patients with OA and RA was also compared. METHODS: Expression of alpha v and beta 3 was examined immunohistochemically in normal synovial tissue and in synovial tissue from patients with OA and RA. The effect of proinflammatory cytokines and of a synovial fluid of a patient with RA on the expression of the alpha v and beta 3 subunits of cultured FBS was determined by flow cytometry. Binding of OA and RA-FBS to VN was quantified using adhesion assays and the effect of interleukin 1 beta (IL1 beta) and tumour necrosis factor alpha (TNF alpha) on adhesion was measured. The specificity of the adhesion was tested by inhibition studies using monoclonal antibodies to integrin subunits. RESULTS: In in situ studies normal SLC showed a parallel distribution of alpha v and beta 3 subunits. OA-SLC strongly and uniformly expressed alpha v whereas RA-SLC showed heterogeneous expression of alpha v. In situ both OA-SLC and RA-SLC lacked the expression of the integrin subunit beta 3. In in vitro studies, OA-FBS and RA-FBS did not differ as regards expression of alpha v and beta 3, and VN attachment. Binding of RA-FBS to VN was partially blocked by antibodies against alpha v, beta 1, and beta 3 subunits, whereas only antibodies against alpha v and beta 3 inhibited the binding of OA-FBS to VN. The proinflammatory cytokines TNF alpha and IL1 beta increased the expression of alpha v and beta 3, and the VN binding of OA-FBS, whereas alpha v and beta 3 expression, and VN binding were downregulated in RA-FBS. Similar effects were found when the synovial fluid of an RA patient was used. CONCLUSION: The integrin subunit beta 3 seems to be one partner but not the major one with which the subunit alpha v forms functional vitronectin receptors in OA-FBS and RA-FBS. The interaction between synovial cells and inflammatory cytokines seems to be different for OA and RA; the basis for this difference, however, remains to be established.
10685457 [Rheumatoid arthritis preceding microscopic polyangitis. Report of two cases]. 2000 Jan INTRODUCTION: Although joint manifestations are common in microscopic polyangiitis (MPA), including arthralgia reported in 15-65% of cases and arthritis in 6-17%, there have been only two published cases of polyarthritis as the first manifestation of the disease. We report on two new cases. EXEGESIS: A 71-year-old woman had symmetric polyarthritis of the hands which initially suggested the existence of seronegative rheumatoid arthritis. A 52-year-old woman had seropositive asymmetric oligoarthritis. The diagnosis was not established until renal insufficiency appeared, prompting a renal biopsy which showed in both cases an extra-capillary glomerulonephritis and an anti-myeloperoxydase (p-ANCA) assay which was postive in both patients. The incidence and specificity of antineutrophil cytoplasmic antibodies (ANCA), including MPA, in rheumatoid arthritis are reviewed. CONCLUSION: Our two observations show that in cases of polyarthritis or oligoarthritis with renal involvement, testing for and typing of ANCA should be performed so as not to misdiagnose vasculitis.
9808394 Treatment of rheumatoid arthritis with a peptide diet: a randomized, controlled trial. 1998 Elemental diets provide food in its simplest formulation and have been used in the treatment of rheumatoid arthritis (RA) and other chronic inflammatory diseases. Such a diet is supposed to be less antigenic to the human immune system than normal food. The aim of this study was to evaluate the clinical effect of an artificial peptide diet as a temporary supplement to conventional treatment. Patients with active RA were single-blindly randomized either to a liquid elemental peptide-diet for four weeks or to continuation of the usual food (control group). In the diet group all normal foods were renounced. Thirty patients were included and followed for six months. The outcome measurements were pain intensity, morning stiffness, HAQ-score, number of swollen joints, joint tenderness, erythrocyte sedimentation rate, and patient's global assessment of health. Two of the fifteen patients assigned to the diet dropped out. The diet resulted in a transient but statistically significant improvement in the average level of pain (P = 0.02), in HAQ-score (P=0.03), and a significant reduction in Body Mass Index (P=0.001). Only one patient in the diet group had a clear remission. Side-effects were frequent but compliance good. The study showed that the peptide diet can improve some subjective and objective disease parameters. Due to the low remission ratio the peptide diet is not a treatment of choice in unselected RA-patients. but the peptide diet might be beneficial to a subset of RA-patients, e.g. patients where foods aggravate disease activity.
10725752 Activation of the IL-4 STAT pathway in rheumatoid synovium. 2000 Apr 1 STATs act as second messenger after binding of a signaling molecule to its receptor. IL-4 STAT is directly involved in the IL-4-dependent gene transcription in the nucleus. We examined the expression and activation of IL-4 STAT and its related kinase Jak-1 in rheumatoid synovium. Rheumatoid arthritis (RA) synovial frozen sections of patients with short-term (<1 year) and long-term disease (>2 years) were examined using in situ hybridization and immunohistochemistry. IL-4 STAT mRNA could be detected in synovium of patients with short-term and long-term RA. The most intensive expression of IL-4 STAT mRNA could be seen in follicular inflammatory infiltrates. In the synovial lining, both fibroblasts and macrophages expressed IL-4 STAT mRNA. IL-4 STAT and Jak-1 protein was expressed by synoviocytes, and up-regulation could be induced after stimulation with IL-4. Activation of IL-4 STAT was reflected by phosphorylation of IL-4 STAT. The results indicate that IL-4 STAT is involved in key pathomechanisms in RA synovium and that IL-4 STAT-dependent pathways operate in early and late stages of the disease and presumably contribute to inhibitory immune mechanisms in RA synovium.
11324696 A molecule basis for the HLA association in rheumatoid arthritis. 2000 Rheumatoid arthritis (RA) is a common chronic autoimmune disease that primarily affects the joints. The etiology of RA is unknown, and the pathogenesis is only poorly defined. One of the few clues to the understanding of the pathogenesis of RA is the observation that the disease is associated with genes in the major histocompatibility complex (MHC). Recent structural and functional studies provide molecular insight into the role of MHC genes in RA susceptibility. This insight provides an important basis for further understanding of the disease mechanism, generation of humanized animal models for RA, and the development of new immunomodulatory drugs with a minimum of unwanted side effects.
11549672 Urocortin expression in synovium of patients with rheumatoid arthritis and osteoarthritis: 2001 Sep Peripherally produced CRH acts as a local auto/paracrine proinflammatory agent. Urocortin is a new member of the CRH family that acts through the family of CRH receptors. In this study, we demonstrated that the expression of urocortin mRNA in synovia of patients with rheumatoid arthritis was greater than that of patients with osteoarthritis. Also, we detected urocortin and CRH receptor immunoreactivity in the synovial lining cell layer, subsynovial stromal cells, blood vessel endothelial cells, and mononuclear inflammatory cells from the joints of rheumatoid arthritis and osteoarthritis patients. The expression of immunoreactive urocortin was significantly greater in rheumatoid arthritis than osteoarthritis (P < 0.0001) and correlated with the extent of inflammatory infiltrate. CRH receptor immunoreactivity was strong in mononuclear inflammatory cells of rheumatoid arthritis synovia. Urocortin stimulated IL-1beta and IL-6 secretion by human peripheral blood mononuclear cells in vitro. These findings suggest that, like CRH, urocortin is present in peripheral inflammatory sites, such as rheumatoid synovium, and acts as an immune-inflammatory mediator.
11550962 Carpal collapse in rheumatoid arthritis--prevalence and clinical significance: a prelimina 2001 Sep OBJECTIVE: To evaluate the prevalence and clinical significance of carpal collapse in Mexican women with rheumatoid arthritis (RA). METHODS: We evaluated the carpal height ratio (CHR) of 97 women with RA and 90 healthy women. Using plain radiographs of both hands, measurements were performed by 2 radiologists in a single blind fashion. We analyzed functional class, characteristics and duration of the disease, and presence of rheumatoid factor (RF). RESULTS: CHR values of the controls were 0.49+/-0.02 (values reported in American Caucasian women are 0.54+/-0.04). Thirty-five patients had carpal collapse (defined as CHR < or = 0.43) in the right hand, 30 in the left hand, and 23 bilaterally. Carpal collapse was associated with RF seropositivity and roentgenographic degree of progression (p < 0.01), as well as with cumulative dose of steroids. As 95% of the patients were right-handed, dexterity was not apparently affected. We observed no differences in Health Assessment Questionnaire, functional class, or disease duration between patients with and those without carpal collapse. CONCLUSION: The definition of carpal collapse may have ethnic related differences. Carpal collapse is common in Mexican women with RA and it is not an indicator of functional limitations.
11594238 Comparison of rheumatoid arthritis care costs in patients starting therapy with leflunomid 2001 Sep OBJECTIVE: To identify differences in rheumatoid arthritis (RA) care costs and utilization among patients receiving therapy with leflunomide (LEF) or etanercept (ETA). STUDY DESIGN: A retrospective cohort analysis of patients diagnosed with RA and starting treatment with LEF or ETA. METHODS: Patients diagnosed with RA and receiving newly prescribed LEF or ETA in 1998 were identified from a database containing patient-level medical and pharmaceutical claims. Patients were subsequently observed for 6 months. RA-related treatment charges during the observation period were compared between cohorts. RESULTS: A total of 527 LEF- and 281 ETA-treated patients were identified. The 2 cohorts were comparable with respect to demographics, comorbid conditions, and concomitant medication use, although LEF recipients were, on average, older than ETA recipients (mean age 52.97 versus 48.43 years; P < .0001). ETA recipients had higher mean 6-month postdiagnosis charges than LEF recipients ($7722.01 +/- $5285.20 versus $3301.84 +/- $4054.75; P < .0001). This difference was primarily related to differences in RA-related pharmacy charges ($5877.78 +/- $2237.68 versus $1877.23 +/- $1258.05; P < .0001). CONCLUSIONS: Compared with charges in the ETA group, RA care costs in the LEF group were significantly lower during the 6 months after the initiation of therapy. The difference in mean total RA-related charges was attributable mainly to the difference in RA-related pharmacy charges.
9643222 Characteristics of rheumatoid arthritis patients with self-reported sicca symptoms: evalua 1997 Dec OBJECTIVES: To examine the prevalence of sicca symptoms in rheumatoid arthritis (RA)-patients, and to evaluate medical, salivary, and oral parameters in matched subgroups of patients with and without sicca symptoms as well as in healthy controls. PATIENTS AND METHODS: The prevalence of self-reported sicca symptoms was examined by a postal questionnaire in a representative cohort of RA-patients (n = 105, aged 52-74 years, disease duration 10-20 years, 77% females, 56% RF-positive). Patient subgroups and controls (9-10 in each group) underwent examinations of disease activity, blood analyses, tests of tear and salivary secretion, and examination of oral mucosa and microflora. Analyses of salivary acidic proline-rich proteins (PRPs), statherin and histatins were performed. RESULTS: One or more sicca symptoms were reported by 65% of RA-patients. Sicca patients (having > or = 4 sicca symptoms) had a more active and severe disease with higher scores for disability, fatigue and tender joints than patients without such symptoms. Other significant findings in the sicca group were lower values of unstimulated whole saliva, output of PRPs, statherin and histatins in submandibular saliva, and higher counts of oral Candida species. CONCLUSIONS: Sicca symptoms were prevalent in RA. Qualitative and quantitative salivary tests distinguished between sicca and non-sicca RA-patients, though overlap was considerable for some parameters.
11764208 Effects of pulse methylprednisolone on macrophage chemotactic protein-1 and macrophage inf 2001 Dec OBJECTIVE: To determine the effect of pulse methyprednisolone (PMP; 1000 mg) on the expression of monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory protein (MIP)-1alpha in rheumatoid synovial membrane. METHODS: Seven patients with rheumatoid arthritis (RA) were studied. Arthroscopically-directed synovial biopsies were taken before and 24 hours after treatment with intravenous PMP. Synovial membranes were stained by immunohistochemical techniques with monoclonal antibodies against MCP-1, MIP-1alpha and CD68 (a macrophage marker). Quantitation of staining was performed by computer-assisted color video image analysis. RESULTS: PMP therapy was associated with a rapid (within 24 hours) and substantial decrease in the expression of MCP-1 and MIP-1alpha expression by a mean of 55% (p = 0.05) and 45% (p = 0.03), respectively, with no effect on CD68 expression in the synovial lining layer. There was no significant change in MCP-1, MIP-1alpha or CD68 expression in the synovial sublining. CONCLUSION: PMP therapy rapidly reduces MCP-1 and MIP-1alpha levels in the synovial lining layer without a fall in macrophage numbers. It thus appears that the initial effect of PMP is that of reducing macrophage activation.