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ID PMID Title PublicationDate abstract
8478866 Sensitivity to change of rheumatoid arthritis clinical trial outcome measures. 1993 Mar OBJECTIVES: To present the properties of an efficiency measure that may be used to make statistical comparisons of sensitivities of trial outcome measures. To use this measure to examine the relative sensitivities of several common rheumatoid arthritis (RA) trial outcome measures in 2 different trial settings. METHODS: Efficiency is expressed as the mean change divided by the standard deviation of change. Variability and correlations of efficiencies for typical RA trial outcomes are described. RESULTS: From among a variety of joint assessments and other clinical measures, pain and global measures, and health status and laboratory measures, the joint tenderness and pain measures were the most sensitive, both in a trial of nonsteroidal antiinflammatory drugs (NSAID) and in a set of second-line drug trials. Measures with rather different sensitivities in the 2 types of trials were erythrocyte sedimentation rate (low sensitivity in the NSAID trial) and physician and patient global measures (higher sensitivity in the NSAID trial). CONCLUSION: The use of statistical information on efficiency estimates allows for a variety of comparisons of measures and may inform the selection of outcome measures for clinical trials.
1472121 Lymphocyte responses to DR4/1-restricted peptides in rheumatoid arthritis. The immunodomin 1992 Dec OBJECTIVE: Peptides presented by DR4/1 may be involved in the pathogenesis of rheumatoid arthritis (RA). T cell responses to DR4/1-restricted peptides unrelated to the causative antigen may be altered in RA. Thus, DR4/1-restricted lymphocyte responses in healthy volunteers and patients with RA were determined. METHODS: Peripheral blood lymphocytes (PBL) and synovial lymphocytes were cultured with synthetic peptides spanning the 19-kd Mycobacterium tuberculosis (MT) protein. RESULTS: 3H-thymidine uptake by PBL from 5 of 7 healthy individuals and 5 of 7 RA patients increased in response to the N-terminal peptide (residues 1-20). Eleven fresh synovial fluid and 4 fresh synovial tissue (ST) lymphocyte samples did not proliferate in response to any of the peptides. However, the same T cell epitope was identified by ST lymphocytes when these were precultured. The N-terminal peptide was not a common antibody-binding site, unlike several of the other peptides. CONCLUSION: Similar responses by RA and normal PBL to a DR4/1-restricted immunodominant T cell epitope on the 19-kd MT protein were observed. The responses were more readily detected in PBL than in synovial lymphocytes. These observations may be relevant for assessing unrelated synthetic peptides in the development of DR4/1-restricted peptide immunotherapy.
8642067 Circulating antibodies directed against conjugated fatty acids in sera of patients with mu 1996 Mar Using an adapted ELISA assay, we have tested sera from multiple sclerosis (MS) patients for antibodies directed against ten fatty acids conjugated to bovine serum albumin. In serum samples from 68 MS patients and 20 patients suffering from rheumatoid arthritis (RA), a significant antibody titer elevation to the ten tested fatty acids was found when compared to sera of 40 healthy subjects and 82 patients with other neurological and autoimmune diseases. G-200 purified IgM of MS patients reacted specifically with the aliphatic chains with an avidity of 3 x 10(-7) M. These results suggest that in MS and RA, autoepitopes on cell membranes that are normally hidden from the immune system become immunogenic. This may arise because of previous membrane disruption by oxidative processes.
1379131 IL-4 down-regulates the surface expression of CD5 on B cells and inhibits spontaneous immu 1992 Aug There is evidence to suggest that CD5+ B cells may be associated with autoimmunity, e.g. they are increased in patients with rheumatoid arthritis (RA). In this study, we found that the expression of CD5 on RA B cells increased spontaneously, following culture for up to 4 days in vitro in the absence of T cells, supporting the idea that the CD5+ B cell possesses distinctive features. The spontaneous increase of CD5 expression was down-regulated by recombinant IL-4 (rIL-4). Other cytokines studied (rIL-1 alpha, rIL-2, rIL-5, rIL-6) did not alter CD5 expression. Studies of antibody production showed that rIL-4 could reduce spontaneous production of total IgG and IgM in non-stimulated RA T plus B cell cultures. Spontaneous production of IgM rheumatoid factor (IgM-RF), measured by a newly developed avidin-biotin complex ELISA, was also reduced by rIL-4. Furthermore, rIL-4 reduced the increase in IgM-RF production observed on stimulation with Staphylococcus aureus Cowan I (SAC) or pokeweed mitogen (PWM). Thus, IL-4 might act as a regulator of the development of abnormal B cell differentiation in patients with RA.
8675829 Pustular psoriasis induced by hydroxychloroquine: a case report and review of the literatu 1996 May A variety of pharmacologic agents have been known to induce pustular psoriasis. We describe a patient with a positive personal and family history of psoriasis who developed an extensive annular pustular eruption 3 weeks after starting hydroxychloroquine (Plaquenil) for arthritis. The drug was discontinued, and she received 3 weeks of systemic and topical corticosteroids; in spite of the therapeutic intervention, showers of new lesions appeared daily, and progressed to involve 75% of the body. The development of new lesions stopped, and the older lesions began to clear after one dose of 7.5 mg of methotrexate. Subsequently, methotrexate therapy was stopped because of mild transaminase elevation; the pustular lesions then flared. New lesions stopped appearing after four doses of weekly methotrexate. The patient remains clear of lesions 6 months later.
8023707 Increased native chemiluminescence in granulocytes isolated from synovial fluid and periph 1994 Mar Polymorphonuclear leukocytes (PMNs) isolated from peripheral blood and synovial fluid of patients with rheumatoid arthritis and from peripheral blood of volunteers were stimulated with 12-phorbol-13-myristate acetate (PMA). No significant differences in luminol-amplified chemiluminescence were found between different patients and control groups. However, two distinct patterns of native chemiluminescence were observed. Type I showed no, or only a small, increase in native chemiluminescence with integral counts over 30 min less than 3 x 10(5) cpm, and the majority of samples from volunteers were of this type. Type II was characterized by a burst of native chemiluminescence starting 8 to 15 min after cell stimulation. It was found in most PMN samples from patients with rheumatoid arthritis. Integral counts over 30 min were always higher than 10(6) cpm and as high as 10(8) cpm in some cases. A strong inhibition of the Type II native chemiluminescence was caused by desferal, catalase, thiourea, and glutathione. However, the luminol-amplified chemiluminescence remained unchanged or was only slightly decreased under the same experimental conditions. Sodium azide strongly inhibited both kinds of luminescence. Hydroxyl radicals, formed in a Fenton reaction, may be important intermediates in the Type II native chemiluminescence.
8325042 Acemetacin in the long-term therapy of rheumatoid arthritis. 1993 An open label study was carried out to assess the long-term use of acemetacin in patients suffering from rheumatoid arthritis. One hundred and two patients were treated with acemetacin, some patients for up to a 12-month period. Analysis of efficacy showed that acemetacin therapy was associated with statistically significant sustained improvements in the target variables of duration of morning stiffness, Ritchie articular index and left and right grip strength. With regard to tolerability, a number of adverse events were recorded but were generally reported as either mild or moderate. In total, 28,988 patient days' treatment with acemetacin were completed and acemetacin proved an effective and well-tolerated long-term therapy in patients with rheumatoid arthritis.
8847766 Health care utilization and outcomes among persons with rheumatoid arthritis in fee-for-se 1996 Oct 2 OBJECTIVE: To compare health care utilization and outcomes over an 11-year period among persons with rheumatoid arthritis (RA) in fee-for-service and prepaid group practice settings. DESIGN: Cohort of persons with RA followed up for as long as 11 years. The principal measures were obtained from an annual structured telephone interview conducted by a trained survey worker. SETTING: Persons with RA presenting to a random sample of community rheumatologists in northern California. PATIENTS: Patients were enrolled in 2 cycles: in 1982 and 1983 and in 1989. Study rheumatologists listed all persons meeting criteria for RA presenting to their offices over a 1-month period. Of the 1062 so listed, we enrolled 1025, or 96.5%. Of the 1025 persons with RA, 227 (22.2%) reported receiving care in prepaid group practice settings. MAIN OUTCOME MEASURES: As of the end of 1994, 5295 person-years of observation were available for the analysis of the annual level of the utilization and outcome measures; 341 persons had been followed up for all 11 years of the study. The main utilization outcomes measured included office visits, outpatient surgeries, hospital admissions, and painful joints. RESULTS: The persons with RA in fee-for-service and prepaid group practice settings did not differ in the quantity of health care used in any 1 year for either RA or non-RA reasons. Among those followed up for all 11 years, the persons in fee-for-service and prepaid group practice settings did not differ in the cumulative quantity of health care used over the entire period of study. The 2 groups did not differ on any outcome measure on either an annual or long-term basis. The results of mortality analyses were inconsistent: using Kaplan-Meier estimates, the persons with RA in prepaid group practice settings survived significantly longer (P<.05 by long-rank test); using Cox proportional hazards methods, the proportion dying each year did not differ signficantly. CONCLUSIONS: We could find no evidence that persons with RA in fee-for-service and prepaid group practice settings received different quantities of health care or experienced different outcomes on either an annual or long-term basis.
7694163 [Hematopoietic growth factors as supportive treatment in drug-induced agranulocytosis]. 1993 Oct 16 This article describes the use of granulocyte macrophage colony stimulating factor and granulocyte colony stimulating factor in two patients with drug induced granulocytopenia. A granulocyte count > 1 x 10(9)/l was obtained after 7 days' treatment. These results suggest that the haematopoietic growth factors shortened the period of agranulocytosis and subsequently may improve the survival of these patients.
7994906 Antibodies to EYRKK vesicular stomatitis virus-related peptide account only for a minority 1994 Dec Previous studies demonstrated a possible antigenic relation between the carboxyl terminal portion of anti-Ro60kD autoantigen and a nucleocapsid protein (N) of vesicular stomatitis virus (VSV). In order to investigate whether anti-Ro60kD autoantibodies react with the VSV homologous region of the Ro60kD protein we synthesized, according to Merrifield's method, the EYRKKMDI octapeptide (8p) sharing a common sequence with the N protein of VSV. Sera from 61 patients with autoimmune rheumatic diseases (34 systemic lupus erythematosus (SLE), 21 Sjörgren's syndrome (SS) and six rheumatoid arthritis (RA)) as well as 59 from normal blood donors were tested for the presence of anti-Ro60kD autoantibodies by ELISA and immunoblot (IB) and anti-8p antibodies by ELISA. Antibodies to 8p were found in 9/31 of anti-Ro60kD IB-positive sera, 5/30 of anti-Ro60kD-negative sera and 2/59 of normal control sera. The concordance between the anti-8p ELISA and the anti-Ro60kD IB was very poor (chi 2 = 0.71, P = 0.4) in contrast to the anti-Ro60kD ELISA and the anti-Ro IB (chi 2 = 27.6, P = 10(-7)). Subsequent affinity purification of the anti-8p antibodies from a strong positive anti-8p and anti-Ro60kD SLE serum yielded 95% depletion of the anti-8p activity and 37% reduction of the anti-Ro60kD activity. Inhibition assays with the affinity-purified anti-8p antibodies demonstrated that the octapeptide gave 94.5% inhibition of the anti-Ro60kD activity, while Ro60kD protein led to 42.3% inhibition of the anti-8p. Preincubation of the serum with the octapeptide produced 4% inhibition of anti-Ro60kD ELISA. These results indicate that the anti-8p antibodies account only for a minority of the anti-Ro60kD autoantibodies.
7912930 Treatment of refractory rheumatoid arthritis with a monoclonal antibody to intercellular a 1994 Jul OBJECTIVE: To assess the safety and efficacy of a monoclonal antibody (MAb) to intercellular adhesion molecule 1 (ICAM-1; CD54) in rheumatoid arthritis (RA). METHODS: A phase I/II, open-label, dose-escalation study of 32 patients. RESULTS: During treatment, a peripheral CD3+/CD4+ lymphocytosis was noted, and several patients demonstrated transient cutaneous anergy, which suggests that therapy modified T cell recirculation. Thirteen of the 23 patients who received 5 days of treatment demonstrated clinical improvement through day 29, and 9 of 23 through day 60. Adverse effects were minor and transient. CONCLUSION: Anti-ICAM-1 MAb therapy was well tolerated, resulted in a transient alteration in T lymphocyte recirculation, and effected clinical improvement in some RA patients.
1466604 Does the locus on chromosome 11 implicated in susceptibility to HLA-DR4 dependent type I d 1992 Nov There is a polygenic component to rheumatoid arthritis (RA) in addition to the known association with HLA-DR4. It has previously been shown in another autoimmune disease (type I diabetes mellitus) that a gene on chromosome 11p can act with HLA-DR4 to enhance susceptibility (relative risk 5-6). It is therefore possible that this locus may also affect the development of RA. Genotype frequencies at this locus, defined by a dimorphic Fok 1 restriction site, were compared in 139 healthy controls and 213 patients with classical/definite RA. In contrast with diabetes there was no increase in genotypes lacking the Fok 1 site, either in the rheumatoid group overall (125/211 compared with 86/139 controls) or in the DR4 positive rheumatoid group (76/140 compared with controls). These results indicate that the interaction between DR4 and a locus on chromosome 11p is not common to all DR4 associated autoimmune diseases.
7682539 Analysis of corneal and conjunctival microenvironments using monoclonal antibodies. 1993 Apr PURPOSE: The authors phenotypically compared epithelial and nonepithelial components of human corneal and conjunctival microenvironments using a panel of monoclonal antibody reagents that included markers of epithelial cell maturation, markers of mesodermal-derived fibrous tissue and vessels, markers of specific keratins, and markers of major histocompatibility complex Class I and II antigens. METHODS: Corneoscleral rims obtained after trephination of the donor button for use in penetrating keratoplasty procedures were studied. RESULTS: A comparison of cornea and conjunctiva with anti-epithelial and antikeratin antibodies demonstrated that corneal and conjunctival keratinocytes undergo similar antigenically defined pathways of maturation. However, the reactivity of antibody 12/1-2 (antibody against low molecular weight keratins) with conjunctival but not corneal basal cells suggested differences in keratin expression between the two epithelial types. Using antibodies against major histocompatibility complex Class I and II antigens, it was demonstrated the two tissues were similar with Class I determinants found on all epithelial, stromal, and endothelial cells, and Class II determinants found on Langerhans' cells, vessels, and a subset of stromal cells. CONCLUSIONS: The availability of tissue-specific markers of epithelial and nonepithelial components of the cornea and conjunctiva should be of use in the study of the roles the ocular microenvironment might play in the pathogenesis of ocular inflammatory diseases.
7966062 Underrecognized postdosing reactions to methotrexate in patients with rheumatoid arthritis 1994 Jul OBJECTIVE: To report previously underrecognized postdosing side effects of methotrexate (MTX). METHODS: Over a one and a half year period, in 2 practices, all patients with rheumatoid arthritis (RA) receiving weekly MTX, and volunteering symptoms within a few hours of MTX dosing were carefully questioned concerning the nature of the postdosing reaction. RESULTS: Of 356 patients, 36 (10%) reported a previously underemphasized postdosing reaction consisting of arthralgias/myalgias, fatigue/malaise or both. Sixteen patients discontinued MTX primarily because of this side effect. CONCLUSION: In these patient populations, postdosing reactions were the 2nd most common side effect (after gastrointestinal) leading to MTX withdrawal.
7769238 Assaying tumor necrosis factor concentrations in human serum. A WHO International Collabor 1995 May 11 A collaborative study involving several international research groups was conducted in order to test the validity and reproducibility of tumor necrosis factor-alpha (TNF) measurements in serum. 58 serum samples, nine of them spiked with recombinant human TNF, were aliquoted and distributed blindly to 11 different laboratories. 20 samples were obtained from cerebral malaria patients, 20 from septic shock patients, eight from patients with rheumatoid arthritis and ten from normal blood donors. The serum samples were assayed for TNF using various immunoassays (ELISA), radioimmunoassays (RIA) and bioassays. Interassay coefficient of variance was analysed. Substantial differences were observed on terms of sensitivity and results obtained with the different commercial and in-house assays. The level of sensitivity was highest with ELISAs and bioassays. RIAs yielded the highest concentrations of TNF in the same samples as compared to those obtained by ELISAs and bioassays. These data emphasize the necessity of establishing international standards for cytokine assays in order to render the interpretation of biological and medical data more reliable.
8976638 Human osteoclast formation and bone resorption by monocytes and synovial macrophages in rh 1996 Nov OBJECTIVE: To determine whether synovial macrophages and monocytes isolated from patients with rheumatoid arthritis patients are capable of differentiating into osteoclastic bone resorbing cells; and the cellular and humoral conditions required for this to occur. METHODS: Macrophages isolated from the synovium and monocytes from the peripheral blood of rheumatoid arthritis patients were cultured on bone slices and coverslips, in the presence and absence of UMR 106 rat osteoblast-like cells, 1,25-dihydroxy vitamin D3 (1,25(OH)2D3) and macrophage colony stimulating factor (M-CSF), and assessed for cytochemical and functional evidence of osteoclast differentiation. RESULTS: Isolated calcitonin receptor (CTR), tartrate resistant acid phosphatase (TRAP), and vitronectin receptor (VNR) negative, CD11b and CD14 positive monocytes and macrophages differentiated into CTR, TRAP, and VNR positive multinucleated cells capable of extensive lacunar bone resorption when co-cultured for 14 d with UMR 106 cells in the presence 1,25(OH)2D3 and M-CSF. CONCLUSIONS: Mononuclear phagocytes (monocytes and macrophages) from rheumatoid arthritis patients are capable of differentiating into multinucleated cells showing all the cytochemical and functional criteria of mature osteoclasts. Synovial macrophage-osteoclast differentiation may represent an important cellular mechanism in the bone destruction associated with rheumatoid arthritis.
1317086 Talocrural arthrodesis with absorbable screws, 12 cases followed for 1 year. 1992 Apr In 11 patients, 12 arthrodeses of the ankle joint were performed by using absorbable self-reinforced poly-l-lactide (SR-PLLA) or polyglycolide (SR-PGA) screws. 8 patients had posttraumatic arthrosis, 3 rheumatoid arthritis, and 1 rigid flexion contracture of the ankle due to neuropathy. The average follow-up time was 14 (7-22) months. Solid fusion was achieved in 11 of 12 cases in 9(6-16) weeks.
7747133 Local versus systemic immunoreactivity to collagen and the collage-like region of C1q in r 1995 In this paper we discuss recent data concerning immunoreactivity on the one hand to the cartilage derived molecule type II collagen (CII) and on the other hand to the complement factor C1q, in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). By using the ELISPOT method we have been able to show that production of antibodies to CII and to C1q is common in inflamed joints but not in the periphery of RA-patients, whereas production to C1q is commonly seen in the circulation of active SLE patients. Previously an immunological cross-reactivity has been described between these two proteins. The possibility of in vivo cross-reactivity between these two molecules might have consequences for the different disease manifestations in RA and SLE. This paper also stresses the importance of single cell analysis of antibody production when evaluating local antibody production in different body compartments and also when the aim is to assay changes in antibody production over time.
7917356 Posterior left ventricular pseudoaneurysm after aortic valve replacement in a patient with 1994 Jul A 58-year-old man with seropositive rheumatoid arthritis underwent successful aortic valve replacement because of severe aortic regurgitation. One year later, prosthetic valve endocarditis was suspected clinically and he was referred for echocardiography. On transthoracic echocardiography an unusual echo-free space adjacent to the inferobasal segments of the left ventricle and extending behind the left atrium was visible. No further diagnostic information could be obtained from precordial examinations. Biplane transesophageal echocardiography demonstrated the presence of a pulsatile pseudoaneurysm of the left ventricle arising posteriorly, close to the anulus of the mitral valve. There was no evidence of endocarditis.
1599808 Current issues of methotrexate and cyclosporine. 1992 Jun Methotrexate given in weekly oral-pulse regimens is rapidly becoming the most popular of the antirheumatic drugs. It seems to act relatively quickly (within 6 to 8 weeks) and patients continue to take it for a longer period of time than other antirheumatic drugs. This issue of long-term hepatotoxicity still has not been clarified, and concerns are now being raised regarding increased infection rates and whether methotrexate should be stopped before joint replacement surgery. Methotrexate, however, remains a very easy drug to use, although in the future it will probably be used as part of combination therapy. Although several clinical trials have demonstrated efficacy for cyclosporine in active rheumatoid arthritis, problems with renal toxicity are still significant. The majority of patients exhibit a rise in the serum creatinine level, although this returns to a normal level when cyclosporine is ceased. In view of this, cyclosporine is likely to remain a drug used in selected, severe cases not responding to other agents.