Browse

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

ID PMID Title PublicationDate abstract
8348280 A 6-month randomized dose range study of OM-8980 in rheumatoid arthritis. 1993 Aug Sixty patients with active RA were evaluated over 6 months in a double-blind randomized dose range multicentre study comparing the efficacy and tolerance of three different doses of the slow-acting anti-rheumatic bacterial extract OM-8980 (6, 24 and 48 mg of active principle). No patients were withdrawn during the study. At the end of the 6-month trial, significant improvements were observed for the different RA signs and symptoms (Ritchie index, morning stiffness, swollen joints, grip strength, ESR, pain scale and categories) as well as for the concomitant intake of symptomatic drugs in the 24-mg dose group with respect to the 6-mg group and without significant differences between the 24- and 48-mg groups. Tolerance was very good with nine minor and transient side effects (five itching and four diarrhoea) reported altogether by seven patients, without establishment of a dose-effect correlation. In conclusion, the two higher doses of OM-8980, 24 and 48 mg, were significantly more efficient than 6 mg, with the effect of the 24-mg dose being even slightly superior to the 48-mg dose, confirming the former as the optimal and well-tolerated dose for the treatment of RA.
7821955 Human monoclonal rheumatoid factors: incidence of cross-reactions with tissue components a 1994 Sep Human monoclonal antibodies with rheumatoid factor (RF) activity, derived from lymphocytes from the synovial tissue of rheumatoid arthritis (RA) patients and the peripheral blood of healthy individuals were examined for cross-reactivity with tissue and cellular antigens. The majority of IgM RF from RA patients (68%) showed reactivity with at least one component, and were frequently multispecific. A very significantly smaller proportion (28%) of the RF derived from healthy individuals demonstrated reactivities against tissue/cellular antigens (P = 0.004). RF from RA patients most commonly reacted with gastric glands (61%), nuclei (50%) and smooth muscle (50%), whereas RF from healthy donors most commonly reacted with gastric glands (20%), smooth muscle (16%), endothelium (16%) and glomeruli (16%). The most striking difference between the two groups was the reactivity with nuclear components, demonstrated by 50% of the RA RF, but by none of the healthy donor RF. As the two groups of antibodies share the same specificity for IgG Fc, but show differences in variable region segment usage, we investigated the relationship between VH gene usage and tissue/cell cross-reactivity using these antibodies and anti-blood group antibodies. Antibodies using VH3 or VH4 gene segments showed a very significantly greater frequency of tissue/cell reactions than those using VH1 (P = 0.0095 and 0.0004 respectively).
1730286 Isolation and characterization of tissue inhibitors of metalloproteinases (TIMP-1 and TIMP 1992 Jan 13 The tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2 were purified to apparent homogeneity from human rheumatoid synovial fluid (HRSF). The inhibitors were isolated by dissociation of non-covalent gelatinase/TIMP complexes. TIMP-1 migrated as a single polypeptide with Mr 28,500 on SDS-PAGE, while the Mr of TIMP-2 was 21,000. The inhibitory activity was stable under heat and acid pH. N-terminal sequence data were obtained for the first 15 residues of both inhibitors and showed identity to the human fibroblast inhibitors TIMP-1 and TIMP-2. This is the first demonstration that TIMP-1 and TIMP-2 can be directly purified from human rheumatoid synovial fluid. The complex formation between the metalloproteinase inhibitors and leucocyte metalloproteinases was shown by immunoblotting.
7962553 Dominant clonotypes in the repertoire of peripheral CD4+ T cells in rheumatoid arthritis. 1994 Nov Clonal expansion of T cell specificities in the synovial fluid of patients has been taken as evidence for a local stimulation of T cells. By studying the T cell receptor (TCR) repertoire of CD4+ T cells in the synovial and peripheral blood compartments of patients with early rheumatoid arthritis (RA), we have identified clonally expanded CD4+ populations. Expanded clonotypes were present in the peripheral blood and the synovial fluid but were not preferentially accumulated in the joint. Dominant single clonotypes could not be isolated from CD4+ cells of HLA-DRB1*04+ normal individuals. Clonal expansion involved several distinct clonotypes with a preference for V beta 3+, V beta 14+, and V beta 17+CD4+ T cells. A fraction of clonally related T cells expressed IL-2 receptors, indicating recent activation. The frequencies of clonally expanded V beta 17+CD4+ T cells fluctuated widely over a period of one year. Independent variations in the frequencies of two distinct clonotypes in the same patient indicated that different mechanisms, and not stimulation by a single arthritogenic antigen, were involved in clonal proliferation. These data support the concept that RA patients have a grossly imbalanced TCR repertoire. Clonal expansion may result from intrinsic defects in T cell generation and regulation. The dominance of expanded clonotypes in the periphery emphasizes the systemic nature of RA and suggests that T cell proliferation occurs outside of the joint.
8148867 Rehabilitation parameters in total knee replacement patients undergoing epidural vs. conve 1994 Feb Epidural analgesia for total knee replacement (TKR) surgery has been proposed as a means of enhancing patient comfort, thereby expediting rehabilitation and reducing hospital stay. This study was done to determine differences in rehabilitation parameters of range of motion and mobility in patients receiving epidural vs. conventional (intravenous) analgesia following TKR surgery. Chart reviews were done of 52 patients who underwent consecutive unilateral TKR, with 26 patients in each analgesia group. There were 21 males and 31 females, ages 24-88 years (median 65), with diagnoses of osteoarthritis (45), rheumatoid arthritis (4), and other (3). The surgeon, procedure, type of prosthesis, and physical therapy protocol were the same for all subjects. Demographics, range of motion, distance walked, assistance required for gait and transfers, assistive device, and exercise competence data were studied at the first postoperative day and at time of discharge. No significant difference was found in the length of stay at the p < .05 level. Significant differences at the first postoperative day favored the epidural group: in knee flexion range--median difference was 0.26 rad [95% confidence interval (CI): 0.09-0.52, p < .05] ie., 15 degrees (95% CI: 5-30); in total range of motion--median difference was 0.30 rad (95% CI: 0.09-0.58, p < .05), ie., 17 degrees (95% CI: 5-33); and in assistance required for gait and transfers (p < .05). At discharge, the epidural group required significantly less assistance (p < .05). There was a trend toward greater walking distance in the epidural group, who walked a median of 15.2 m farther than the conventional analgesia group.(ABSTRACT TRUNCATED AT 250 WORDS)
7927499 Antigen-presenting capacity of rheumatoid synovial fibroblasts. 1994 Jun In normal, healthy joints, synovial fibroblasts do not express major histocompatibility complex (MHC) class II molecules. However, in inflamed joints of rheumatoid arthritis (RA) patients, synovial fibroblasts show an abundant expression of MHC class II. Does this increase in expression have functional consequences for antigen presentation to T cells? To date, the precise role of synovial fibroblasts in antigen presentation has not been documented. Here, we show by three different examples that cultured synovial fibroblasts with interferon-gamma (IFN-gamma)-induced MHC class II expression are capable of processing soluble protein for presentation to CD4+ T cells. First, the antigen-presenting cell (APC) function of synovial fibroblasts was studied in an autologous model. From synovial tissue of a RA patient both a fibroblast cell line and a tetanus toxoid (TT)-specific CD4+ T-cell line were generated. A dose-dependent TT response was observed only when TT was presented by IFN-gamma-pretreated synovial fibroblasts. As more direct evidence for MHC class II-restricted antigen presentation, the response of a Mycobacterium tuberculosis-specific CD4+ T-cell clone isolated from rheumatoid synovial fluid was demonstrated in the presence of synovial fibroblasts. The response was DR4Dw4-restricted and could be inhibited by monoclonal antibody (mAb) to HLA-DR. In addition, the lymphokine secretion pattern of the synovial T-cell clone did not differ qualitatively upon antigen-specific stimulation using peripheral blood mononuclear cells (PBMC) or synovial fibroblasts as APC. In order to provide evidence for intracellular antigen processing we next examined the response of a M. leprae-specific T-cell clone with known epitope specificity. Our data suggest that synovial fibroblasts are not passive bystanders, but can become active participants in the development and maintenance of chronic inflammation.
8702433 Inhibition of Fas antigen-mediated apoptosis of rheumatoid synovial cells in vitro by tran 1996 Aug OBJECTIVE: To investigate the mitogenic and anti-apoptotic effects of transforming growth factor beta 1 (TGF beta 1) on rheumatoid synovial cells in vitro. METHODS: Synovial cells were cultured with or without TGF beta 1. After incubation, the proliferative response of synovial cells and the expression of Fas antigen and bcl-2 on synovial cells were examined. Finally, Fas antigen-mediated apoptosis of synovial cells was investigated by the addition of anti-Fas antibody. RESULTS: TGF beta 1 enhanced the proliferation of synovial cells in a dose-dependent manner. In addition, Fas antigen expression on synovial cells was inhibited by the addition of TGF beta 1 with up-regulation of bcl-2 expression. The addition of anti-Fas antibody induced synovial cell apoptosis. However, stimulation of synovial cells with TGF beta 1 became markedly resistant to Fas antigen-mediated apoptosis. The results were not affected by the addition of a neutralizing antibody to platelet-derived growth factor type AA (PDGF-AA), which suggests that the effect of TGF beta 1 on synovial cells was promoted via PDGF-AA-independent mechanisms. CONCLUSION: Our results suggest that TGF beta 1 promotes synovial cell proliferation through its mitogenic effect on synovial cells and interference with the apoptotic process mediated by the Fas antigen, resulting in the perpetuation of the synovial hyperplasia in patients with rheumatoid arthritis.
8500934 [Acetabulum without cement. Short-term results of a series of 112 threaded cups]. 1993 Between January 1982 and December 1987 we used 112 threaded acetabular cups in 102 patients undergoing total hip replacement. The clinical and radiographic results of 107 implants are reported in this survey. Using the functional grading of the hip advocated by Merle d'Aubigné and Postel, 62% can be classified as excellent, very good or good. On x-ray only 35% of the cups show neither radiolucency at the bone-implant interface nor migration of the component. There is a statistically significant correlation between a radiolucency in 2 of the 3 areas at the bone-implant interface and the clinical result. The revision rate for failure of the cup is 11.6% (13 implants). The actuarial survival of the threaded cup decreased from 0.95 in the 1st year to 0.75 in the 5th year after implantation. Analysis of our failures and of published data suggest that the problem lies in the lack of primary bone integration. We describe our difficulties in assessing risk factors, in interpreting the radiographs and in the intraoperative determination of component instability. The disappointing short term results have prompted us to abandon the use of threaded cups.
1563236 Update on autoantibodies to intracellular antigens in systemic rheumatic diseases. 1992 Mar Autoantibodies to nuclear and intercellular antigens have been established as important diagnostic and specific markers for many of the systemic rheumatic diseases. Diseases that have demonstrated specific markers and profiles of autoantibodies include systemic lupus erythematosus, scleroderma, Sjörgren's syndrome, mixed connective tissue disease, drug-induced lupus, and dermatomyositis/polymyositis. The study of molecular biology of the various autoantigens and autoantibodies has led to a better understanding of function and tissue pathogenesis. The clinical diagnostic significance of the various autoantigens and autoantibodies to nuclear and intracellular antigens is discussed in this article.
9208591 [CuZn-SOD determination of sera in patients with rheumatic diseases]. 1996 Feb Superoxide anion (O2.-) plays an important part in reactive oxygen species (ROS). In order to explore its effect on the pathogenesis of rheumatic diseases, authors had determined CuZn-SOD contents of sera in 132 subjects involving the patients of rheumatic diseases (SLE, RA, etc), non-rheumatic diseases and normal controls by using enzyme linked immunosorbent assay (ELISA). The results showed the followings: CuZn-SOD contents of 27 normal subjects: 98.80 +/- 20.74 ng/ml (x +/- s); that of 27 non-rheumatic diseases cases: 72.24 +/- 16.60 ng/ml (x +/- s); of 22 SLE cases: 56.56 +/- 19.27 ng/ml (x +/- s); of 27 RA cases: 61.56 +/- 20.53 ng/ml (x +/- s); of 29 other rheumatic diseases cases: 68.97 +/- 17.79 ng/ml (x +/- s). Statistical test was made: both CuZn-SOD contents of rheumatic disease and non-rheumatic disease were lower than that of normal subjects with more significant difference (P < 0.001); compared with that of non-rheumatic diseases patients, SLE cases had significant difference (P < 0.01); RA cases had significant difference (P < 0.05); other cases of rheumatic diseases had no statistical differrence (P > 0.05). Above results suggest that superoxide anion is a non-specific inflammatory mediator which contributes to disorders with inflammatory damages (rheumatic or non-rheumatic diseases), where CuZn-SOD content tested was obviously lower than normal subjects; among the rheumatic disease patients, CuZn-SOD contents of the sera of SLE patients were the lowest because of its more autoimmune antibody, more severe inflammatory and immunological reaction. This work laid the theoretical and experimental foundation for the clinical application of exogenous CuZn-SOD in the treatment of rheumatic diseases. Combined use of CuZn-SOD scavengers may get better result because of the complexibility of ROS inflammatory mechanism.
7693840 Cell contact between T cells and synovial fibroblasts causes induction of adhesion molecul 1993 Nov Human activated T cells adhere to synovial fibroblast-like cells in vitro. The present study was conducted to investigate the consequences of T cell-synovial fibroblast interactions with regard to induction of adhesion molecules and proinflammatory cytokines. A sensitive Western blot technique, polymerase chain reaction (PCR) amplification, and fluorescence-activated cell sorter (FACS) analysis were used to analyze the induction of VCAM-1 and ICAM-1 expression in T cell-synovial fibroblast cocultures. VCAM-1 and ICAM-1 expression could be induced in synovial fibroblast-like cells by 2 h. PCR amplification showed that both forms of VCAM-1 mRNA are found after the interaction of synovial fibroblasts with T cells. Up-regulation of VCAM-1 and ICAM-1 was confined to synovial fibroblasts; T cells did not express VCAM-1 or increased ICAM-1. In contrast to the T cell-synoviocyte interaction, the interaction between T cells and dermal fibroblasts resulted in the up-regulation of ICAM-1 but not VCAM-1, suggesting tissue-specific regulation of VCAM-1. The T cell-synovial fibroblast interaction also resulted in increased levels of tumor necrosis factor (TNF), interferon-gamma, and interleukin-6 in coculture supernatant. Of the neutralizing antibodies used against these cytokines, only anti-TNF could significantly inhibit VCAM-1 and ICAM-1 expression. When T cells were separated from synoviocytes by a chamber that allowed medium exchange but no cell contact, VCAM-1 and ICAM-1 failed to be up-regulated and cytokine accumulation in cocultures was drastically reduced. Our results demonstrate mutual cell activation of T cells and synoviocytes upon cell contact as shown by the release of T cell- and synoviocyte-specific cytokines and suggest a cell contact-mediated and T cell-initiated mechanism for the chronic accumulation and retention of mononuclear cells via VCAM-1/ICAM-1 by synovial fibroblasts in the rheumatoid synovium.
1386608 Restricted heterogeneity of T cell receptor transcripts in rheumatoid synovium. 1992 Aug RA is characterized by massive proliferation of synovial tissue, accompanying infiltration of the tissue with CD4+ T lymphocytes, and a genetic linkage to the MHC antigen HLA-DR4. Since T cells are restricted by class II MHC molecules such as DR4, this suggests a direct role for these CD4+ cells in pathogenesis. To investigate T cell receptor (TCR) usage in RA, we used oligonucleotide primers specific for each of the major alpha and beta TCR subfamilies to amplify cDNA derived from whole synovium or synovial tissue T cell lines in a family-specific manner. Detection of amplified DNA was facilitated by utilizing oligonucleotide probes derived from the constant regions of the TCRs. The TCR repertoire present in the synovial T cell lines was quite heterogeneous, with an average of 15 alpha chains and 15.8 beta chains detected. When synovial tissue was analyzed, the predominant TCR subfamilies detected tended to be more restricted, with an average of 4.6 alpha chains and 8.6 beta chains detected. This compared with an average of six alpha chains and 12 beta chains in nonrheumatoid synovial samples. The average percentage of synovia positive per TCR beta family was significantly lower for RA versus non-RA specimens (46.1 vs 65.6%, P = 0.034). These findings indicate that while a polyclonal population of T cells is present in RA synovium, the predominant patterns of TCR transcript expression may be somewhat more restricted, suggesting that TCR-based therapy of RA is possible.
8507219 Levels of synovial fluid interleukin-1 receptor antagonist in rheumatoid arthritis and oth 1993 Jun OBJECTIVE: To measure synovial fluid (SF) levels of interleukin-1 receptor antagonist (IL-1ra) and to determine the capacity of SF neutrophils (PMN) to synthesize and release IL-1ra. METHODS: A sensitive and specific enzyme-linked immunosorbent assay was used to measure SF IL-1ra protein concentrations and IL-1ra production by isolated SF PMN: RESULTS: SF IL-1ra levels were elevated in 13 of 16 samples from patients with rheumatoid arthritis (RA) (mean 17.1 ng/ml), in 6 of 18 samples from patients with infectious or inflammatory, non-RA arthropathies (mean 10.6 ng/ml), and in none of 11 noninflammatory SF samples. SF IL-1ra levels correlated with SF PMN concentrations (r = 0.680, P < 0.00001). Isolated SF PMN contained preexisting IL-1ra protein in the absence of messenger RNA (mRNA). In addition, both lipopolysaccharide and granulocyte-macrophage colony-stimulating factor induced modest increases in IL-1ra mRNA by cultured SF-PMN. CONCLUSION: IL-1ra levels are increased in > 80% of RA SF samples. SF PMN produce IL-1ra, possibly contributing to the levels of IL-1ra present within the SF.
1575744 Interleukin-1 beta stimulates cytosolic phospholipase A2 in rheumatoid synovial fibroblast 1992 Apr 30 Phospholipase A2 (PLA2) activities in rheumatoid synovial fibroblasts (RSF) stimulated with interleukin-1 beta (IL-1 beta) were investigated. RSF incubated in the presence of IL-1 beta (120 pg/ml) for 18 h secreted 35 fold more PGE2 than did those incubated without IL-1 beta. IL-1 beta treatment did not increase the level of secretory PLA2 (sPLA2) activity or sPLA2 protein in the conditioned medium or subcellular fractions of lysed RSF. In contrast, the cell-associated PLA2 activity increased 3 to 4 fold in IL-1 beta stimulated RSF when compared with the control. The IL-1 beta stimulated, cell-associated PLA2 required submicromolar concentrations of calcium for activity, a characteristic consistent with the calcium sensitivity of cytosolic PLA2 (cPLA2) activity reported in other cell types, such as U937 cells. These findings demonstrate that an elevation in a cytosolic PLA2, rather than a sPLA2, is associated with increased PGE2 production in IL-1 beta stimulated RSF.
7685671 Rheumatoid factors from patients with rheumatoid arthritis react with Des-Lys58-beta 2m, m 1993 Jun Ten polyclonal IgM rheumatoid factor (RF) preparations, affinity-purified from IgG columns, from patients with rheumatoid arthritis were studied for their ELISA reactivity with native beta 2m in parallel with Lys58-cleaved beta 2m and Des-Lys58-beta 2m, the latter representing cleavage products of the native molecule present in some pathologic human sera. Most RF showed positive reactions with the native form of beta 2m but reduced reactivity for the cleaved forms of beta 2m. Reactions between cleaved beta 2m and RF, in solution, were demonstrated by inhibition of RF binding to native beta 2m by preincubation with a range of concentrations of Des-Lys58-beta 2m. By contrast, eight of nine murine MoAbs to human beta 2m showed approximately equivalent binding to native beta 2m, Lys58-cleaved beta 2m, and Des-Lys58-beta 2m. Reactions between individual human RF and the altered forms of beta 2m (Lys58-cleaved beta 2m and Des-Lys58-beta 2m) appeared to parallel the previously determined beta 2m single amino acid specificities, in that RF showing strong reactivity with Lysine 58 also showed a significant diminished reactivity with the Des-Lys58-beta 2m lacking the critical lysine residue. The present studies demonstrate that while human RF react with Lys58-cleaved beta 2m or Des-Lys58-beta 2m, preferential reactivity is observed for native unaltered beta 2m.
8639176 Elevated serum level of soluble HLA class I antigens in patients with systemic lupus eryth 1996 May OBJECTIVE: To examine the clinical significance of serum soluble HLA class I antigens (sHLA class I) in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). METHODS: Serum levels of sHLA class I were measured by enzyme-linked immunosorbent assay, using a monoclonal antibody against monomorphic determinant of HLA class I (W6/32) and an enzyme-labeled polyclonal antibody to human beta 2-microglobulin. RESULTS: The serum sHLA class I concentration was 1.85 +/- 1.15 micrograms/ml (mean +/- SD) in 27 patients with SLE (P < 0.0001 versus normal controls, P = 0.0001 versus RA), 0.61 +/- 0.34 micrograms/ml in 16 patients with RA (P = 0.02 versus normal controls), and 0.41 +/= 0.20 micrograms/ml in normal controls. The HLA class I levels were significantly correlated with the SLE Disease Activity Index (r = 0.62, P = 0.0004) and with a reduction of CH50 levels (r = -0.60, P = 0.0007). A longitudinal analysis of patients with SLE indicated that serum sHLA class I levels fluctuated in conjunction with other disease activity markers. CONCLUSION: Serum sHLA class I may be useful as a disease activity marker of SLE. The mechanism of secretion and the physiologic role of sHLA class I require further study.
8278816 Limitations of randomized clinical trials to recognize possible advantages of combination 1993 Oct Potential advantages of combination second-line drug therapy in rheumatoid arthritis (RA) may not be detectable in standard randomized controlled clinical trials, despite excellent design and performance. This results from intrinsic limitations of usual clinical studies, such as a short time frame, patient selection, and insufficient numbers of patients. Examples of selected clinical protocols in rheumatic diseases that illustrate these problems are presented. In systemic lupus erythematosus, many well-designed and -performed trials comparing combinations of cytotoxic drugs and corticosteroids with corticosteroids alone were inconclusive. However, combination therapy was superior in three types of studies: a 15-year clinical trial, a pooled analysis of multiple trials, and longitudinal databases of unselected patients. In RA, a 48-week study indicated no differences in results of treatment with auranofin, methotrexate, and the combination of these two drugs. In contrast, a clinical database from 15 rheumatology practices indicates that methotrexate was continued for 5 years by more than 50% of patients, compared with fewer than 10% for auranofin. A subset from the clinical database of courses of second-line drugs over 1 year (rather than 5 years), for only the initial course of a second-line drug (rather than any course), was examined. Using these selected data, which mimic the conditions of the clinical trial, no significant differences were seen in continuation of methotrexate versus auranofin. This observation suggests that intrinsic limitations, including patient selection, insufficient patient numbers, and a short time frame, may render it difficult (or impossible) to document the efficacy of combination therapy in RA using standard randomized controlled clinical trials.
8348040 [The effect of new biologically active substances on effector T-lymphocytes in vitro]. 1993 Mar Levamisole has been demonstrated to stimulate the activity of T effectors in patients with rheumatic arthritis directly and indirectly via production of the factors influencing effector functions. The organosilicon compound minval was beneficial both in patients and donors. Its activity was mediated by the production of factors in donors, whereas in patients it showed direct and indirect actions, being higher than that of levamisole. The bioflavonoid derived from the Rosa L. root was shown to exert no action on T-effector function.
1418006 Effects of interleukin-6 on the metabolism of connective tissue components in rheumatoid s 1992 Oct OBJECTIVE: High levels of interleukin-6 (IL-6) have been found in the synovial fluid of patients with rheumatoid arthritis (RA). We undertook the present study to investigate the role of IL-6 in this disease. METHODS: We examined the effects of IL-6, in comparison with IL-1, on the biosynthesis of extracellular matrix macromolecules and of matrix-degrading proteinases in rheumatoid synovial fibroblasts. RESULTS: In rheumatoid synovial fibroblasts, IL-6 by itself enhanced the production of plasminogen activator, its inhibitor, and tissue inhibitor of metalloproteinases, whereas it did not modulate the biosynthesis of precursor of matrix metalloproteinase 1 (proMMP-1) (tissue collagenase), proMMP-3 (stromelysin), or connective tissue components. However, IL-1-induced production of proMMP-1 and proMMP-3 was preferentially augmented by IL-6. CONCLUSION: These results suggest that in RA, IL-6 may participate along with IL-1 in fine tuning of the catabolism of connective tissue components, by modulating the balance between connective tissue-degrading enzymes and their inhibitors.
1482861 Preliminary evaluation of learning via the AI/LEARN/Rheumatology interactive videodisc sys 1992 AI/LEARN/Rheumatology is a level three videodisc system to teach clinical observational skills in three important diseases: rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. The AI/LEARN software was developed on an independent authoring system called GALE designed for MS-DOS based computers. The purpose of this paper is to present preliminary data about the efficacy of teaching by the use of an interactive videodisc system as evaluated by examinations centered upon disease-oriented learning objectives and by attitude questionnaires. We tested the efficacy of the AI/LEARN/Rheumatology system using both medical students and residents taking the rheumatology elective. Data collected were on learning, attitudes, and ranking of curricular elements of the rotation. We kept records on the student time and search path through the interactive videodisc system. Control data were collected during 1990, before the AI/LEARN/Rheumatology program was available. Data for the treatment groups were collected during 1991 and 1992, while the trainees used the AI/LEARN/Rheumatology system. The basic difference between the control year and the treatment year curricula was the substitution of AI/LEARN/Rheumatology for three hours of lecture covering the three target diseases. AI/LEARN/Rheumatology was as effective as traditional methods of instruction as measured by scores on a multiple choice test. Student and resident learning was related to the time spent on the system. Students and residents ranked the AI/LEARN/Rheumatology system as the single most helpful learning tool in their 8 week rheumatology block, ranking it above the examination of patients.