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ID PMID Title PublicationDate abstract
11575911 Primary osteoarthritis of the hip: etiology and epidemiology. 2001 Sep Primary osteoarthritis (OA) of the hip has a distinct etiology and epidemiology compared with other types of arthropathy in the hip joint. Arthritis of the hip can be secondary to conditions such as osteonecrosis, trauma, sepsis, or rheumatoid arthritis. Certain conditions, such as congenital hip disease and slipped capital femoral epiphysis, involve predisposing anatomic abnormalities; in such cases, the term "secondary OA" is used. When either an anatomic abnormality cannot be determined or other specific causative entities are not identified, primary OA is the diagnosis of exclusion. The prevalence of hip OA is about 3% to 6% in the Caucasian population and has not changed in the past four decades. In contrast, studies in Asian, black, and East Indian populations indicate a very low prevalence of hip OA. Statistics on patients who underwent total hip replacement for primary OA in San Francisco and Hawaii demonstrate a virtual absence of the condition in Asians and low rates in the black and Hispanic populations. Family studies from Sweden, Britain, and the United States show increased rates of hip OA in first-degree relatives of the index patient when compared with the normal population. Occupations requiring heavy lifting, farming, and elite sports activity are associated with increased rates of hip OA. The low prevalence of hip OA in Asian and black populations in their native countries; the low incidence of total joint replacement for primary OA in Asian, black, and Hispanic populations in North America; and the familial association of hip OA in Caucasians all suggest that genetic factors may be involved in the occurrence of this disease.
11002624 A comparative study of subsyde-CR versus meloxicam in rheumatic disorders. 2000 May A prospective, randomised comparative clinical study was conducted in adult patients of either sex presenting with articular and non-articular rheumatic conditions commonly encountered in clinical practice Rheumatoid arthritis, osteo-arthritis, cervical spondylosis, and lumbago/sciatica were the most frequent conditions encountered in both the groups, followed by others like tenosynovitis, frozen shoulder, prolapsed disc, fibrositis, myositis, sprains, strains and so on. The drugs that were employed for therapy were diclofenac in a controlled release formulation employing the DRCM technology (subsyde-CR) and meloxicam in a standard formulation marketed in our country. Both drugs were well tolerated and found to be effective in reducing the signs and symptoms of the disease entities throughout the study period, but subsyde-CR was observed to produce a somewhat greater reduction in signs and symptoms scores that meloxicam, a difference that could be possibly attributed to the greater efficacy of subsyde-CR in non-articular rheumatic conditions. On the basis of the available literature on diclofenac and meloxicam as well as the DRCM technology in formulating subsyde-CR, it is reasonable to conclude that a controlled release formulation of diclofenac based on the DRCM technology offers a safe and effective alternative to other non-steroidal anti-inflammatory drugs such as meloxicam.
10907175 Vasculitis of the female genital tract with clinicopathologic correlation: a study of 46 c 2000 Jul Forty-six cases of vasculitis affecting the female genital tract are described; only 41 similar cases have been previously reported, either as case reports or small series. The age range of the patients was from 22 to 80 years, and most of them presented with abnormal bleeding or were being treated conditions unrelated to the vasculitis. There were 39 hysterectomy specimens (26 of which were derived from total abdominal hysterectomies) and seven specimens of the cervix only. The vasculitis was confined to the cervix in 30 of the 46 cases; in 24 of these, the entire uterus was available for examination. In 23 cases, only a single vessel was involved, and in the other 23 there was more extensive vessel involvement. In all cases, the involved vessels were arterioles and small arteries. In 42 cases, the arteritis was of the polyarteritis nodosa (PAN) type, and in four, of the giant cell type (GCA). Follow-up ranged from < 1 year to 23 (mean, 3) years. Systemic manifestations were previously diagnosed or subsequently developed in only four patients, three with PAN and one with GCA; in each of them, the genital tract vasculitis was found only in the cervix (in one of these, however, the specimen was a loop excision of the cervix and the rest of the uterus was not assessable). The three patients with PAN subsequently developed extragenital PAN (one case), PAN and rheumatoid arthritis (one case), or PAN and polymyalgia rheumatica (one case). The patient with GCA had previously documented temporal arteritis and temperomandibular arthritis. The findings in this series and in previously reported cases indicate that vasculitis of the female genital tract is only rarely associated with systemic vasculitis.
10488739 Identification of a natural soluble form of human CD5. 1999 Aug CD5 is a 67 kDa type I glycoprotein which belongs to the Scavenger Receptor Cysteine-Rich (SRCR) family of receptors. This family includes either cell-surface (e.g. CD6) or secreted (e.g. Spalpha) proteins implicated in the development of the immune system and the regulation of immune responses. In this study, we purified and characterised a circulating natural soluble CD5 form (nsCD5) which is indistinguishable (in apparent molecular mass, glycosylation pattern, and antibody reactivity) from a recombinant soluble CD5 form (rsCD5) composed of the three extracellular SCRC domains. The nsCD5 is a N-glycosylated 52 kDa molecule present in normal human serum and in supernatants of in vitro phorbol ester- and CD3-stimulated peripheral blood mononuclear cells. The nsCD5 concentration in sera from healthy donors is relatively low (median 1.75 ng/ml, rn=166) and is similar to that found in sera from patients suffering of various autoimmune (systemic lupus erythematosus, primary Sjogren syndrome, rheumatoid arthritis) and non-autoimmune (chronic renal failure, B-cell chronic lymphocytic leukemia) disorders. In vitro experiments indicate that nsCD5 is released by proteolytic cleavage of the membrane form. These results represent the first evidence of proteolytic release of a transmembrane SRCR family member following cell activation.
10048522 A preliminary report: cementless trapeziometacarpal arthroplasty. 1999 Jan A cementless ball and socket trapeziometacarpal arthroplasty was used for the treatment of Eaton and Littler stage II and III trapeziometacarpal osteoarthritis. Forty-two joints were placed in 36 patients between 1986 and 1992. Five joints in 4 patients required revision. Thirty-four joints in 30 patients were evaluated with a mean follow-up period of 47 months (range, 15-86 months). Of the 33 monitored patients (39 joints), 79% reported good to excellent pain relief and excellent functional improvement and 12% reported poor to fair pain relief and functional improvement. Five joints required revision surgery and constituted 13% of the original arthroplasties. Thirty-three functional tests were graded before and after surgery and improvement was noted in all categories. Dramatic improvement was noted in the typical complaints for trapeziometacarpal joint disease, which are encountered in the activities of daily living. Radiolucent lines were present in 13 of 25 implants (52%), which were radiographically monitored. Radiographic loosening was present in 32%; 12 were around the trapezial component and 1 was around the metacarpal component. Radiographic loosening did not correlate with less satisfactory clinical results. Cementless trapeziometacarpal arthroplasty provides an operative alternative to arthrodesis in properly selected patients with trapeziometacarpal joint osteoarthritis. This joint is not intended to replace excisional or ligament reconstruction tendon interposition arthroplasty in lower demand patients or in those with pantrapezial arthritis. It also is not recommended in patients with rheumatoid arthritis or poor bone stock. It offers the advantages of maintaining excellent motion and stability. The cementless arthroplasty failures can be effectively salvaged by converting them to ligament reconstruction tendon interposition arthroplasty.
10036584 SAA1 alleles as risk factors in reactive systemic AA amyloidosis. 1998 Dec SAA1 is the predominant isoform of acute phase human SAA deposited as AA amyloid fibrils in reactive systemic amyloidosis. It has recently been reported that in the Japanese population, in whom the SAA1 gamma allele occurs with a frequency of 37%, possession of, and especially, homozygosity for this allele is a significant risk factor for AA amyloidosis in adult patients with rheumatoid arthritis (RA). In contrast we report here that in a control sample of 95 healthy adult male Caucasians the SAA1 gamma allele occurs at the much lower frequency of 5.3% and that, among 41 patients with juvenile chronic arthritis (JCA) and AA amyloidosis, there was a highly significantly increased frequency of the SAA1 alpha allele (90.2%), and particularly homozygosity for this allele (80.5%), compared both to the healthy controls (75.8% and 57.9% respectively) and to 8 JCA cases without amyloid (56.3% and 12.5%). A similar trend with respect to frequency of the SAA1 alpha allele and homozygosity for it was observed among 26 adult Caucasian RA patients with AA amyloid and 26 such cases without amyloid, although it did not reach statistical significance. These results suggest that there is probably differential amyloidogenicity amongst the different SAA1 isoforms and indicate that homozygosity for SAA1 alpha and SAA1 gamma in the different populations is a significant risk factor for development of AA amyloidosis. In Caucasian patients with JCA, the presence of the homozygous SAA1 alpha genotype indicates high risk of amyloidosis and should encourage early and aggressive anti-inflammatory therapy to keep circulating SAA levels as low as possible.
9314611 Clinical pharmacokinetics of diclofenac. Therapeutic insights and pitfalls. 1997 Sep Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) of the phenylacetic acid class. When given orally the absorption of diclofenac is rapid and complete. Diclofenac binds extensively to plasma albumin. The area under the plasma concentration-time curve (AUC) of diclofenac is proportional to the dose for oral doses between 25 to 150 mg. Substantial concentrations of drug are attained in synovial fluid, which is the proposed site of action for NSAIDs. Concentration-effect relationships have been established for total bound, unbound and synovial fluid diclofenac concentrations. Diclofenac is eliminated following biotransformation to glucoroconjugated and sulphate metabolites which are excreted in urine, very little drug is eliminated unchanged. The excretion of conjugates may be related to renal function. Conjugate accumulation occurs in end-stage renal disease; however, no accumulation is apparent upon comparison of young and elderly individuals. Dosage adjustments for the elderly, children or for patients with various disease states (such as hepatic disease or rheumatoid arthritis) may not be required. Significant drug interactions have been demonstrated for aspirin (acetylsalicylic acid), lithium, digoxin, methotrexate, cyclosporin, cholestyramine and colestipol.
9291172 A shift in encephalitogenic T cell cytokine pattern is associated with suppression of EAE 1997 Apr Pooled human polyspecific IgG preparations for intravenous use (IVIg) have been used in a number of antibody mediated autoimmune diseases and recently in some T cell mediated disorders including multiple sclerosis, birdshot retinopathy and rheumatoid arthritis. Furthermore, IVIg has been proven beneficial in the corresponding animal models, i.e. experimental autoimmune encephalomyelitis (EAE), experimental autoimmune uveoretinitis and adjuvant arthritis respectively. The exact mechanisms for IVIg action in T cell mediated disorders are still poorly understood. There is evidence that IVIg treatment in vitro and in vivo decreases or changes the kinetics of the secretion by normal PBMC of a number of cytokines and anti-proliferative effect of IVIg on T cells in vitro and in vivo has also been reported. It remains unclear though to what extent the IVIg effects in T cell mediated autoimmunity are related only to non-specific T cell suppression and whether it also reshapes the autoimmune T cell cytokine profile. In this study we demonstrate that IVIg protects against EAE and that this beneficial effect is associated with a decreased proliferation of T cells specific for the immunizing antigen. Moreover, we show that these antigen-specific cells produce low amount of Th1-type cytokines and transfer an attenuated EAE.
9002018 Relapsing polychondritis: clinical and immunogenetic analysis of 62 patients. 1997 Jan OBJECTIVE: In this study we describe clinical and immunogenetic findings in 62 unselected patients with relapsing polychondritis. METHODS: In a multicenter study, clinical data of 26 (41.9%) female and 36 (58.1%) male patients were collected. HLA-DR specificities were identified in 60, and the frequencies were compared with those in healthy controls. RESULTS: The median age at the time of diagnosis was 46.6 years (range 17 to 86). 58 (93.5%) patients had auricular chondritis, 31 (50.0%) ocular symptoms, 35 (56.5%) nasal involvement. Involvement of joints (53.2%), respiratory system (30.6%), skin (24.2%), cardiovascular system (22.6%), central nervous system (9.7%), and kidneys (6.5%) was found as well. 22 (35.5%) patients had associated diseases such as systemic lupus erythematosus or rheumatoid arthritis. Susceptibility to relapsing polychondritis was significantly associated with HLA-DR4 (p < 0.001). There was no difference in the frequency or distribution of DRB1*04 subtype alleles between patients and healthy controls. The extent of organ involvement was negatively associated with HLA-DR6 (p < 0.011). CONCLUSION: Immunogenetic findings as well as similarities and overlapping clinical symptoms with other autoimmune or rheumatic diseases suggest that immunological mechanisms play a major role in the pathogenesis of relapsing polychondritis.
9328126 Anti-Ro fine specificity defined by multiple antigenic peptides identifies components of t 1997 Sep Anti-Ro (or SSA) is a clinically important autoantibody that is found in 25-40% of patients with systemic lupus erythematosus as well as an even greater proportion of patients with Sjögren's syndrome or subacute cutaneous lupus. We have studied the binding of anti-Ro sera to multiple antigenic peptides constructed from the sequence of the 60-kD Ro molecule. The results demonstrate that sera bind these peptides in solid-phase assay. Surprisingly, some of these peptides also form a precipitin line in double immunodiffusion with anti-Ro sera. Formation of lines of identity in double immunodiffusion as well as absorption studies indicate that peptides distant in the primary amino acid sequence and without shared sequence are bound by the same antibody. In addition, data from surface plasmon resonance demonstrate that peptides identified in this manner have protein-protein interactions. Thus, these techniques may identify the components of conformational epitopes.
11764534 Gastrointestinal toxicity associated with nonsteroidal anti-inflammatory drugs. Epidemiolo 2001 Dec The large body of literature on the gastrointestinal side effects of NSAIDs has shown consistently that populations can be identified that have a markedly elevated risk for these iatrogenic conditions. These groups include the elderly, persons with prior history of peptic ulcer disease and its complications, persons receiving anticoagulant and corticosteroid therapy, and persons who require long-term NSAID therapy, especially at high dose. It is possible that several comorbidities (e.g., rheumatoid arthritis) predispose patients to gastrointestinal complications caused by NSAIDs, but few studies have adjusted carefully for the possibility that concomitant medication use (e.g., oral anticoagulants, corticosteroids) or increased NSAID dose may account best for apparent association of comorbidities as a risk factor for serious gastrointestinal events. The role of H. pylori infection in affecting the risk of complicated ulcer disease among NSAID users remains to be fully elucidated. Low-dose aspirin for cardioprotective use is associated with an increased risk for PUBs; when used concomitantly with NSAIDs, this increases the risk of PUBs above that of the NSAID itself. Apart from the physical toll NSAID-related gastrotoxicity places on the patient, there are considerable economic consequences to patients, providers, and society. This cost presents a subject for research for those interested not only in improving the quality of patient care, but also in the prudent use of health care resources.
11177771 Update on synovitis. 2001 Feb Rheumatoid arthritis (RA) is an inflammatory disorder associated with chronic synovitis, eventually leading to cartilage and bone destruction in the joints. Synovitis is associated with the activation of various cells in the synovium including synovial lining cells, interstitial macrophages, endothelial cells, lymphocytes, and fibroblasts. The key mechanisms underlying synovitis include inflammatory cell adhesion and activation, the production of mediators (such as cytokines, chemokines, and growth factors), angiogenesis, joint destruction, fibrosis, and bone resorption. These important events, as well as the role of inflammatory cells, cell surface molecules, and soluble mediators are updated and discussed in this review. Some aspects and strategies of current or future immunotherapy are also discussed because these animal and human trials provide information on the pathogenesis of inflammatory synovitis.
10963468 Conjugated linoleic acid and bone biology. 2000 Aug Osteoporosis, osteoarthritis and inflammatory joint disease afflict millions of people worldwide. Inflammatory cytokines inhibit chondrocyte proliferation and induce cartilage degradation for which part of the response is mediated by PGE2. Excess production of PGE2 is linked to osteoporosis and arthritis and is associated with bone and proteoglycan loss. PGE2 also influences the IGF-I/IGFBP axis to facilitate bone and cartilage formation. Recent investigations with growing rats given butter fat and supplements of CLA demonstrated an increased rate of bone formation and reduced ex vivo bone PGE2 production, respectively. Furthermore, the supplements of CLA isomers resulted in their enrichment in lipids of various bone compartments of animals. The effects of CLA on bone biology in rats (IGF action and cytokines) appear to be dependent on the level of n-6 and n-3 fatty acids in the diet; however, these studies generally showed that CLA decreased ex vivo bone PGE2 production and in osteoblast-like cultures. Anti-inflammatory diets, including nutraceutical applications of CLA, may be beneficial in moderating cyclooygenase 2 (COX-2) activity or expression (influencing PGE2 biosynthesis) and might help to reduce rheumatoid arthritis (secondary osteoporosis). This review summarizes findings of CLA on bone modeling in rats and effects on cellular functions of osteoblasts and chondrocytes. These experiments indicate that CLA isomers possess anti-inflammatory activity in bone by moderating prostanoid formation.
10083965 Psychological and behavioral approaches to pain management for patients with rheumatic dis 1999 Feb This article reviews the efficacy of the psychological and behavioral pain management interventions that have been evaluated among adult patients with rheumatoid arthritis (RA), osteoarthritis (OA), and fibromyalgia (FM). Using published criteria for empirically validated interventions, it is concluded that cognitive-behavioral therapies and the Arthritis Self-Management Program represent well-established treatments for pain among patients with RA and OA. These interventions involve education, training in relaxation and other coping skills, and rehearsal of these skills in patients' home and work environments. There currently are no psychological or behavioral interventions for pain among FM patients that can be considered as well-established treatments. Future intervention research should use clinically meaningful change measures in addition to conventional tests of statistical significance, attend to the pain management needs of children, and assess whether outcomes produced in university-based treatment centers generalize to those in local treatment settings.
9917663 Total knee arthroplasty in patients 55 years old or younger. 10- to 17-year results. 1998 Nov Seventy-four consecutive total knee arthroplasties in 54 patients who were 55 years of age or younger (average age 43 years) were reviewed. All patients had a minimum followup of 10 years with an average followup of 13 years (range, 10-17 years). No patients died or were lost to followup. The preoperative diagnosis was rheumatoid arthritis in 47, gonarthrosis in 12, posttraumatic arthritis in six, osteonecrosis in three, hemophilia in two, and one patient each with pigmented villonodular synovitis, tuberculosis, systemic lupus erythematosus, and achondroplasia. The knee score improved from an average of 36 points (range, 10-80 points) preoperatively to 84 points (range, 37-100 points) at latest followup. The functional score improved from 45 points (range, 0-100 points) to 60 points (range, 0-100 points) at latest followup. Two patients had their implants revised: one at 3 years because of ligamentous laxity and one at 13 years because of aseptic loosening of the tibial component. There were no deep infections. There were no radiographically loose implants at latest followup. The implant survival to revision at 10 years was estimated at 99% (confidence limit, 96%-100%). The implant survival to revision at 15 years was estimated at 95% confidence limit, 88%-100%). Cemented total knee arthroplasty in the young patient is a reliable procedure and has excellent results at 13-year followup with an estimated survivorship of 99% at 10 years.
11200382 Duration of postoperative antibiotic therapy following revision for infected knee and hip 2000 In the period from 1990 to 1998 28 patients (14 males and 14 females) were treated for infected hip (19 cases) and knee (9 cases) arthroplasties. The median age at index operation was 72 y (range 34-82 y) and at revision surgery 74 y (range 36-83 y). The primary diagnosis was osteoarthritis (16 cases), rheumatoid arthritis (5 cases), failed femoral neck fracture (6 cases) and arthritis secondary to congenital hip dislocation (1 case). Nine cases were infected early, i.e. within 3 months postoperatively, and 19 had late infections. The median interval from index operation to diagnosis of the infected arthroplasty was 18 months (range 1-156 months). Postoperatively, all patients received antibiotics based on susceptibility studies of the causative organism according to culture specimens. The erythrocyte sedimentation rate and CRP level were controlled twice a week during hospitalization and antibiotics were continued until normalization of CRP. The indication for the shift from intravenous to oral antibiotics was a rapid fall in CRP. Antibiotic therapy was terminated when CRP was close to or below 10 mg/l and there was evidence of clinical recovery. Based on the screening of ESR and CRP in this study we believe that CRP is a valuable parameter in deciding when to stop antibiotic therapy. However, it is not clear whether a shorter treatment period is effective or not.
10770268 Immunomodulation of experimental autoimmune diseases via oral tolerance. 2000 The concept of oral tolerance refers to a form of peripheral tolerance in which mature lymphocytes in the peripheral lymphoid tissues are rendered nonfunctional or hyporesponsive by prior oral administration of an antigen. The primary mechanisms mediating oral tolerance include deletion, anergy of antigen-specific T cells and active cellular suppression, the primary determining factor being the dose of fed antigen. Low doses favor active suppression, whereas high doses favor deletion and anergy. Active cellular suppression is mediated by the induction of regulatory T cells in the gut-associated lymphoid tissue, which migrate to the systemic immune system. One of the primary mechanisms of active cellular suppression is via secretion of suppressive cytokines such as TGF-beta, IL-4, and IL-10 following antigen-specific triggering. TGF-beta is produced both by CD4+ and CD8+ GALT-derived T cells and is an important mediator of the active suppression component of oral tolerance. CD4+ cells that primarily produce TGF-beta appear to be a unique T-cell subset and termed Th3 cells. Oral tolerance was successfully studied in a variety of experimental models for autoimmune diseases, among them experimental autoimmune encephalomyelitis, experimental arthritis, experimental anti-phospholipid syndrome, experimental autoimmune uveoretinitis, experimental insulin dependent diabetes mellitus (IDDM), and experimental autoimmune myasthenia gravis. The results obtained in experimental animal models have led to the conduction of several clinical trials of oral tolerance in patients with multiple sclerosis, rheumatoid arthritis, uveitis, and IDDM. Conflicting results were obtained, and although some improvement has been noted in some of the patients, broad ranging clinical improvement has not yet been observed. A more accurate choice of antigens, as well as more precise dosing and timing of antigen-administration might lead to better results in the future.
10415727 Fluorogenic MMP activity assay for plasma including MMPs complexed to alpha 2-macroglobuli 1999 Jun 30 Elevated MMP activities are implicated in tissue degradation in, e.g., arthritis and cancer. The present study was designed to measure MMP enzyme activity in plasma. Free active MMP is unlikely to be present in plasma: upon entering the circulation, active MMP is expected to be captured by the proteinase inhibitor alpha 2-macroglobulin (alpha 2M). Reconstituted MMP-13/alpha 2M complex was unable to degrade collagen (MW 300,000) in contrast to the low-molecular-weight fluorogenic substrate (MW < 1500). Limited access of high-MW substrates to the active site of MMPs captured by alpha 2M presents the most likely explanation. Consistently, the high-MW inhibitor TIMP (MW approximately 28,000) was unable to inhibit MMP/alpha 2M enzyme activity, whereas the low-MW inhibitor BB94 (MW approximately 500) effectively suppressed enzyme activity. By using fluorogenic substrates with Dabcyl/Fluorescein as quencher/fluorophore combin-ation, sensitive MMP-activity assays in plasma were achieved. Spiking of active MMP-13 and MMP-13/alpha 2M complex, and inhibitor studies with TIMP-1 and BB94, indicated that active MMPs are efficiently captured by alpha 2M in plasma. MMP activity was even detected in control plasma, and was significantly increased in plasma from rheumatoid arthritis patients.
10193998 Celecoxib, a COX-2--specific inhibitor: the clinical data. 1999 Mar Celecoxib offers the unique therapeutic prospect of alleviating pain and inflammation without the untoward gastrointestinal, renal, and platelet effects associated with conventional nonsteroidal anti-inflammatory drugs. This is possible because celecoxib is a cyclooxygenase-2 (COX-2)-specific inhibiting agent that inhibits the conversion of arachidonic acid to the prostaglandins that mediate pain and inflammation while having no effect on the formation of the prostaglandins that mediate normal homeostasis in the gastrointestinal tract, kidneys, and platelets and that are formed under the control of cyclooxygenase-1 (COX-1). Double-blind clinical trials have demonstrated that celecoxib is as effective in ameliorating the signs and symptoms of osteoarthritis and rheumatoid arthritis as naproxen and as effective as aspirin in reducing pain following dental extraction. Controlled trials have also shown that the incidence of gastroduodenal ulcers and the combined incidence of gastroduodenal ulcers and erosions are significantly lower with celecoxib therapy than with naproxen therapy and are similar to those associated with placebo administration. In a study of platelet function, it was found that a single 650-mg dose of aspirin profoundly diminished platelet function, while therapeutic doses of celecoxib exhibited no such effect. Celecoxib has been shown to be well tolerated, with incidences of adverse events similar to placebo in most instances. In summary, evidence to date indicates that celecoxib is a safe and effective therapeutic modality for the management of arthritis and pain.
9182918 Paclitaxel selectively induces mitotic arrest and apoptosis in proliferating bovine synovi 1997 Jun OBJECTIVE: Rheumatoid arthritis (RA) is characterized by chronic progressive destruction of joints involving several disease processes, such as villous hypertrophy, proliferation of synovial lining cells, and infiltration of inflammatory cells. Synovial cell activation and proliferation is thought to be a key step in the destruction of cartilaginous and bony tissues in RA joints. In view of the invasive properties of synoviocytes in RA, we conducted in vitro studies to determine the mechanism of action of paclitaxel (Taxol) on synoviocytes, which may account for the inhibition of joint destruction found when this agent is administered. METHODS: Cultured synovial cells were treated with various concentrations of paclitaxel and were evaluated by cell viability, fluorescence microscopy, flow cytometry of DAPI-stained cells, and electron microscopy. RESULTS: The data indicated that paclitaxel inhibited synoviocyte proliferation by a G2/M phase block and was toxic to synoviocytes by inducing apoptosis. Confluent cells such as chondroyctes and synoviocytes were not affected by paclitaxel. Synchronization of synovioyctes at the G1/S boundary effectively abolished paclitaxel-induced apoptosis. CONCLUSION: The data indicate that induction of apoptosis in synoviocytes might be dependent on transit through the cell cycle, specifically through G2 and mitosis. Further, paclitaxel was selectively toxic to proliferating synoviocytes but spared nonproliferating synoviocytes and chondrocytes. These results demonstrate that paclitaxel can inhibit synovial cell proliferation and pannus formation in RA joints in vivo. We suggest that paclitaxel be considered as a prototypical compound for a new class of potential chondroprotective agents.