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ID PMID Title PublicationDate abstract
9068280 Cartilage and bone macromolecules in knee joint synovial fluid in rheumatoid arthritis: re 1997 Feb OBJECTIVE: To examine the hypothesis that aggrecan, cartilage oligomeric matrix protein (COMP), and bone sialoprotein (BSP) concentrations in synovial fluid could provide information on variations of progression of joint destruction in rheumatoid arthritis. METHODS: Aggrecan, COMP, and BSP were quantified by enzyme linked immunosorbent assays in longitudinally collected knee joint synovial fluid samples of patients rapidly developing destruction in knees or hips, the "'destructive" group, n = 18, and in patients slowly developing destruction, the "non-destructive" group, n = 25. RESULTS: The aggrecan concentrations decreased from initially high levels (P < < 0.001), and the BSP concentrations increased (P < < 0.001) over time in the destructive group, whereas levels of both markers were low and did not change in the non-destructive group. The COMP levels did not change in any of the groups. The aggrecan concentrations were initially highest in the group developing destructions (P < < 0.001), whereas no difference between the groups was found regarding levels of COMP or BSP in the first sample. CONCLUSIONS: A destructive group was characterised by higher initial aggrecan concentrations and rising BSP concentrations in synovial fluid with time. Quantification of cartilage and bone derived macromolecules contributes to the assessment of extent of tissue destruction and may help in the early identification of patients at risk of rapidly progressing destruction.
10992732 Injectable gold-induced hepatitis and neutropenia in rheumatoid arthritis. 2000 Jul Gold salts have been used for many years in the treatment of rheumatoid arthritis. The common side effects are mucocutaneous reactions, but hepatotoxic reaction and isolated neutropenia are rare complications. We report a 62-year-old woman with rheumatoid arthritis who had developed hepatitis and neutropenia simultaneously after receiving 137.5 mg of sodium aurothiomalate.
9256031 [Crescentic glomerulonephritis in a patient with rheumatoid arthritis]. 1997 Jun A 56-year-old female with rheumatoid arthritis was admitted because of bilateral hip pain. In a few months of her hospitalization, a relatively abrupt renal dysfunction was emerged besides complement breakdown, and renal biopsy revealed crescentic glomerulonephritis. Immunofluorescence study showed peripheral granular deposits of IgG, IgM, and C3 in the glomeruli. Cresents were predominantly composed of macrophages and glomerular epithelial cells. Amyloid nephropathy, renal vasuculitis, and association of other collagen vascular diseases were negligible for the causative factor. It was suggested that immune complexes were formed in the glomeruli, in which both humoral and cellular immune responses were to be induced, that brought cescents formation in the lesions. Crescentic glomerulonephritis in patients with rheumatoid arthritis is rare and a possible pathogenetic mechanisms involved in the development of renal dysfunction are discussed with the special reference to immune complex-induced inflammation.
10646494 Recapitulation of the round-table discussion--assessing the role of anti-tumour necrosis f 1999 Nov Clinical trials specifically targeting and neutralizing the cytokine, tumour necrosis factor (TNF), have recently provided evidence of efficacy and a promise of a novel approach for the treatment and management of rheumatoid arthritis (RA). With the evolving emergence of anti-TNF therapeutics, several unresolved issues have come to light, including the assessment of safety and efficacy of current therapies, study design for new agents and cost-benefit issues. During an international meeting of leading rheumatologists and specialists, the majority opinion regarding the use of anti-TNF therapy was that these agents are most appropriate in patients with active disease who have insufficient response to methotrexate, which is presently considered the standard for RA treatment. Anti-TNF therapy was also recommended in patients with active disease unable to tolerate methotrexate therapy, or who have not responded to at least two other disease-modifying anti-rheumatic drugs (DMARDs). In patients with RA who have serious infection or malignancy, the use of anti-TNF therapies was not advised. Time, experience and clinical data from recently completed and currently ongoing studies of infliximab and etanercept, which will be available in the future, will help determine the ultimate role of such targeted therapeutics. Additional data on anti-TNF therapeutics as monotherapy or in various combinations are still needed to achieve maximum disease control safely with currently available DMARDs.
9226475 Suppression of arthritis by the inhibitors of dipeptidyl peptidase IV. 1997 Jan Dipeptidyl peptidase IV (DP IV, CD26) is a serine exoprotease which selectively cleaves the penultimate proline residue of polypeptides. This enzyme is also expressed as a surface marker on activated T cells. In order to assess the relevance of DP IV in immunological disorders, we evaluated the in vivo effects of specific DP IV inhibitors using two arthritis models, one which was induced by collagen one by alkyldiamine. These animal models share several pathological features associated with rheumatoid arthritis. The transition state substrate analog of DP IV, (S)-Alanylpyrrolidine-boronic Acid (Ala-boroPro), suppressed hind paw swelling, which was associated with collagen-induced and alkyldiamine-induced arthritis. A competitive inhibitor of DP IV, Lys(Z(NO2))-thiazolidide and an irreversible inhibitor, Ala-Pro-nitrobenzoylhydroxylamine also suppressed alkyldiamine-induced arthritis dose-dependently. We also analyzed the pharmacological effects of Lys(Z(NO2))-thiazolidide on several immune responses in vitro, in order to determine its mode of action. This inhibitor suppressed mitogen-induced and antigen-induced proliferation of T cells. However, studies using splenic cells from DP IV deficient rats showed that the inhibition of lymphocyte proliferation was not exerted through the inhibition of DP IV.
10415601 Sex hormones and pregnancy in rheumatoid arthritis and systemic lupus erythematosus. 1999 Jun 22 Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are autoimmune disorders with a preponderance in females. RA and SLE differ in their response to sex hormones. Disease development of RA is mitigated by estrogen and pregnancy whereas SLE tends to flare during pregnancy and in response to estrogen. Pregnancy improves the symptoms of RA in about 75% of pregnant patients, but relapses within six months postpartum in 90% of cases. RA is regarded as a T cell-mediated and TH1 immune response-driven disease. Pregnancy induces a shift from TH1 to TH2 immune response, increasing the anti-inflammatory cytokines IL-4 and IL-10, which may contribute to gestational amelioration of RA. Prospective studies of SLE pregnancies indicate that about 50% of patients experience a flare, however, with no permanent aggravation of the disease. Lupus nephritis, presence of antiphospholipid antibodies, and a previous history of pregnancy loss increase the risk of complications during pregnancy and fetal loss. The marked increase of estrogen and progesterone during pregnancy seems to enhance some of the manifestations of SLE. The shift to a TH2 immune response may trigger SLE manifestations that are dependent on humoral immune responses such as lupus nephritis. Another factor stimulating immune responses is the pituitary hormone prolactin, which has been found elevated in SLE patients of both sexes and correlated to disease activity in several studies. The hyperprolactinemia of lactation seems to influence postpartum behavior of SLE as well as RA.
10990218 Assessing radiographic status of rheumatoid arthritis: introduction of a short erosion sca 2000 Sep OBJECTIVE: Although radiographs are an important marker of rheumatoid arthritis severity, no valid simple scoring method exists. Current scoring systems are cumbersome, difficult to learn, time consuming, and suitable only for experts. In addition, there is no "gold standard" for radiographic severity, so that it is impossible for the clinician, trialist, or researcher to place patients' scores along a continuum of radiographic severity. We investigated the scoring and scaling properties of radiographs read by the Larsen method, and we developed a shortened scale that can be placed in the perspective of a linear severity continuum. METHODS: A total of 3,538 paired hand radiographs obtained over a 24 year period were read by Larsen method and evaluated by Rasch analysis. By iterative methods the number of joints was reduced so that proper fitting, scaling, and dimensionality were obtained. The shortened scale was then tested against the full Larsen scale to determine its ability to detect radiographic progression. RESULTS: A scale consisting of 6 joints on each hand (3 wrist areas and 3 metacarpophalangeal joints) performed as well as the full 28 joint Larsen score, and had improved fit and scaling properties. This Short Erosion Scale (SES) also performed as well as the Larsen score in measuring radiographic progression as measured by comparative effect sizes. In addition, a nomogram was developed to translate SES scores into radiographic severity scores according to a Rasch logit scale. CONCLUSION: We developed a Short Erosion Scale by reducing the number of joints evaluated in the Larsen method from 28 to 12. The scale is at least as sensitive in detecting change as the full Larsen scale. SES fits the Rasch model and is hierarchical and generally well spaced. Graphs and nomograms are available so that intrinsic radiographic severity can be documented. This scale is suitable for use in clinical practice and observational studies, and may be appropriate for clinical trials as well.
11993724 Difference in urinary 11-dehydro TXB2 and LTE4 excretion in patients with rheumatoid arthr 2001 Nov Thromboxane and leukotrienes have been implicated in inflammation. However, the production level of these eicosanoids in patients with rheumatoid arthritis is still unclarified. In the present study, endogenous synthesis of thromboxane and cysteinyl leukotrienes in patients was investigated. The production of eicosanoids in patients is assessed by measuring stable urinary metabolites,11-dehydro thromboxane B2 and leukotriene E4, using gas chromatography/selected ion monitoring and liquid chromatography/tandem mass spectrometry. The level of urinary thromboxane in patients was significantly higher than that in healthy volunteers (P < 0.05). Furthermore, we investigated the effects of administered drugs on the production of these eicosanoids. The urinary thromboxane level of the untreated group (1630 +/- 613 pg/mg creatinine) was much higher than that of healthy volunteers (342 +/- 263 pg/mg creatinine). The level in the group receiving NSAID alone was similar to that in healthy volunteers, and the group receiving steroid alone showed slightly lower thromboxane levels than the untreated group. On the other hand, the leukotriene E4 level in patients (280 +/- 360 pg/mg creatinine) was also significantly higher than that in healthy volunteers (59 +/- 54 pg/mg creatinine, P < 0.05). In particular, the group receiving methotrexate (904 +/- 685 pg/mg creatinine) had higher leukotriene levels than not only healthy volunteers but also other medicated groups. These findings demonstrated that endogenous thromboxane and leukotriene production in patients with rheumatoid arthritis are enhanced, and the effects of medication on the production of these eicosanoids differed in thromboxane and leukotriene E4.
11060691 Soluble cytokine receptors: novel immunotherapeutic agents. 2000 Mar Being mediators of immune and inflammatory reactions, abnormal or excessive production of cytokines is often the main cause of the pathology in many types of disease. Targeting cytokines by means of inhibitory drugs may thus offer a valid therapeutic approach in particular diseases. Soluble forms of cytokine receptors (sCR) normally participate in the control of cytokine activity in vivo by inhibiting the ability of cytokines to bind their membrane receptors and from generating a biological response. The ability of sCR to act as cytokine inhibitors, coupled to their specificity, high affinities and low immunogenicities have prompted considerable interest in their use as immunotherapeutic agents. In fact, many types of sCR have been shown to inhibit the biological activity of their cytokines in vitro and in different experimental models. Several sCR, particularly the soluble TNF receptors sTNFR-I (p55) and sTNFR-II (p75), have been modified by linking them to the Fc portion of human immunoglobulin (e.g., 'immunoadhesins') or by the addition of polyethylene-glycol (PEG) (e.g., 'PEGylation'), in order to enhance their affinity and/or biological half-life. These agents have shown significant therapeutic value in clinical trials of patients with rheumatoid arthritis (RA). Indeed, a sTNFR-II:Fc hybrid molecule (etanercept), the first sCR-derived therapeutic agent to receive approval for human use, is already utilised for the treatment of some forms of RA. Additional applications of this drug in other inflammatory conditions are currently being evaluated, while another sCR-derived agent, a human sIL-4R, is undergoing trials for the treatment of asthma. Many other sCR, such as sIL-1R, sIL-5R, sIFNgammaR, may also have significant potential for the treatment of a wide variety of human diseases.
10544840 Externalization of calpain (calcium-dependent neutral cysteine proteinase) in human arthri 1999 Sep OBJECTIVE: Calcium-dependent neutral cysteine proteinase (calpain) was originally referred to as an intracellular enzyme. However, recently it has come to be considered as an extracellular matrix proteinase, as well having a degrading effect on cartilage proteoglycan. In the present study we sought to determine whether human articular cartilage chondrocytes themselves have the capability to produce and secrete this interesting proteinase. METHODS: Human articular cartilage tissue cultures from osteoarthritic (11 specimens from 7 patients) and rheumatoid arthritic (3 specimens from 2 patients) knee joints were established, and the m-calpain released into the culture medium was concentrated and detected by immunoelectrophoretic blotting. The presence of m-calpain in the arthritic cartilage was also examined by immunohistochemistry before and after culturing. RESULTS: M-calpain was detectable in all of the cartilage tissue culture supernatants (conditioned medium) by western blotting. Positive intracellular immunostaining of m-calpain in chondrocytes was observed in all samples. Furthermore, m-calpain was found to be present in the matrix and on the articular surface of the cartilage in half of the specimens. CONCLUSION: The findings of our experiment suggest that cartilage chondrocytes may actively take part in m-calpain production and that they may have the capacity to release it into the extracellular matrices.
10573760 Why I would not recommend complementary or alternative therapies: a physician's perspectiv 1999 Nov The use of complementary or alternative therapies by patients with rheumatic diseases is widespread and under-reported by patient to physician. The most commonly used forms of therapy are herbal/nutrient supplements, chiropractic, homeopathy, and acupuncture. The use of these therapies for treatment of rheumatic disease is not substantiated by review of the available medical literature. Furthermore, these therapies are expensive and potentially toxic. Incorporation of these treatments into the therapeutic armamentarium of the rheumatologist cannot be recommended until they are shown to be effective, safe, and affordable.
10364916 Complement C1s activation in degenerating articular cartilage of rheumatoid arthritis pati 1999 Mar OBJECTIVE: The first complement component C1s was reported to have novel functions to degrade matrix components, besides its activities in the classic complement pathway. This study explores participation of C1s in articular cartilage degradation in rheumatoid arthritis (RA). METHODS: Normal articular cartilage (n = 6) and cartilage obtained from joints with RA (n = 15) and osteoarthritis (OA, n = 10) were immunostained using anti-C1s monoclonal antibodies PG11, which recognises both active and inactive C1s, and M241, which is specifically reactive to activated C1s. The effects of inflammatory cytokines on C1s production by human articular chondrocytes were also examined by sandwich ELISA. RESULTS: In normal articular cartilage, C1s was negative in staining with both PG11 and M241. In contrast, degenerating cartilage of RA was stained with PG11 (14 of 15 cases), and in most of the cases (13 of 15 cases) C1s was activated as revealed by M241 staining. In OA, C1s staining was restricted in severely degrading part of cartilage (5 of 10 cases), and even in that part C1s was not activated. In addition, C1s production by chondrocytes in vitro was increased by an inflammatory cytokine, tumour necrosis factor alpha. CONCLUSION: These results suggest that C1s activated in degenerative cartilage matrix of RA but not in that of OA. C1s is thought to participate in the pathogenesis of RA through its collagenolytic activity in addition to the role in the classic cascade.
10340639 The change of bone mineral density in secondary osteoporosis and vertebral fracture incide 1999 Causes of secondary osteoporosis are diverse, and bone changes in this condition have been elucidated less than those in primary osteoporosis. In this study, bone mineral density (BMD) was measured in the lumbar spine, distal and proximal sites of the radius, and calcaneus in representative disorders that cause secondary osteoporosis to evaluate its changes. Also, the incidence of nontraumatic vertebral fracture was examined. The subjects were 80 patients with rheumatoid arthritis, 50 patients undergoing glucocorticoid (steroid) therapy, 20 patients with chronic hepatitis, 24 patients with liver cirrhosis, 14 patients with primary biliary cirrhosis (PBC), 26 patients with diabetes mellitus, and 20 postgastrectomy patients; all were ambulatory female outpatients. Two hundred females with primary osteoporosis were examined as a control group. The reproducibility of the measurement of the BMD was satisfactory at about 3% by all methods of measurement employed. Concerning changes in BMD, periarticular trabecular bone density was most markedly reduced in the rheumatoid arthritis group. The patients receiving steroid therapy showed the greatest decreases in the trabecular bone mineral density at the distal 4% of the radius and lumbar spinal BMD. In addition, the threshold of vertebral fracture was higher in those undergoing steroid therapy than in those with primary osteoporosis. The patients with PBC showed the greatest decreases in BMD among patients with chronic liver disorders, and no decrease in BMD was noted in the chronic hepatitis group. BMD was reduced only in the radius in the patients with diabetic mellitus, and it was generally reduced in the postgastrectomy patients. BMD of the calcaneus was not reduced in any group.
10521640 novel Award First Prize Paper. Orthotic management of plantar pressure and pain in rheumat 1999 Oct OBJECTIVE: To investigate the effectiveness of foot orthoses in the management of plantar pressure and pain in subjects with rheumatoid arthritis. DESIGN: A repeated measures study in which the independent variable was orthosis design. Dependent variables, including pressure, gait and pain parameters, were examined using analysis of variance and correlation statistics. BACKGROUND: The aim of orthotic management of the rheumatoid foot is to relieve metatarsalgia through the reduction of metatarsal head pressure. Few studies have investigated the relative effectiveness of different orthosis designs. To date, no studies have examined the relationship between plantar pressure and second metatarsal head pain in rheumatoid arthritis subjects. METHODS: Twelve rheumatoid arthritis subjects with foot involvement and second metatarsal head pain were tested. Four styles of foot orthosis (prefabricated, standard custom moulded, custom with metatarsal bar, custom with metatarsal dome) were compared to a shoe only control. An EMED Pedar system was used to measure plantar pressure during repeated trials of comfortable cadence walking and quiet standing. Reports of subjective pain were recorded for each orthosis as were orthosis preferences. RESULTS: All orthoses significantly reduced pressure beneath the first and second metatarsal heads compared to the shoes only control. The custom moulded orthosis with metatarsal dome was the most effective orthosis for reducing subjective ratings of pain. A significant correlation (r=0.562) was found between ratings of pain and average pressure beneath the second metatarsal head. CONCLUSIONS: Results from this study suggest that average pressure measurement may be a useful indicator in the management of metatarsalgia in RA. Further study is required to improve understanding of the relationship between rheumatoid foot mechanics and pain. RELEVANCE: Appropriate foot orthosis design can substantially improve comfort in RA patients with symptomatic feet. A custom moulded foot orthosis incorporating a metatarsal dome was the most effective design for subjects with painful second metatarsal heads. Foot pressure measurement technology can be a useful adjunct to research and clinical management of the painful rheumatoid foot.
10651080 Oxidant/antioxidant status of plasma samples from patients with rheumatoid arthritis. 1999 This study aims to elucidate plasma oxidant/antioxidant status in patients with rheumatoid arthritis (RA). Fasting blood samples were obtained from 24 patients with RA and 20 control subjects. Antioxidant potential (AOP) value, nonenzymatic superoxide radical scavenger activity (NSSA), and malondialdehyde (MDA) levels were measured to establish plasma oxidant/antioxidant status in the patient and control groups. Patients with RA had lower AOP and NSSA but higher MDA levels than those of the control subjects, which was an indication of reduced antioxidant capacity and oxidant stress in these patients. Results suggest that the antioxidant system is impaired and peroxidation reactions are accelerated in patients with RA. We suppose that therapeutic use of some antioxidants may be beneficial in this regard.
10770099 Benign rheumatoid nodules of childhood. 1999 Jul The nodules associated with rheumatoid arthritis and rheumatic fever appear with other signs of active rheumatic disease. Rheumatoid nodule-like lesions irrelevant to rheumatoid disease occasionally occur in children who are well and have no complaints associated with rheumatoid diseases. Laboratory tests are normal. Children with benign rheumatoid nodule are not at increased risk for rheumatic disease. No therapy or prophylaxis is required. We present a two-year-old girl with a subcutaneous nodule on the right pretibial region who was diagnosed with clinical and histological findings.
10211880 Different mechanisms of synovial hyperplasia in rheumatoid arthritis and pigmented villono 1999 Apr OBJECTIVE: To elucidate the involvement of telomerase activity in the pathogenesis of rheumatoid arthritis (RA) and pigmented villonodular synovitis (PVS). METHODS: Peripheral blood lymphocytes (PBL), synovial infiltrating lymphocytes, and synoviocytes were isolated from peripheral blood samples and synovial tissue obtained from 18 patients with RA, 9 with PVS, 12 with osteoarthritis (OA), and 10 with knee joint trauma. Cellular telomerase activity was measured by the telomeric repeat amplification protocol assay. In RA patients, the telomerase activity level in synovial infiltrating lymphocytes was assessed for correlations with histologic features in rheumatoid synovium. RESULTS: A high level of telomerase activity was detected in the PBL and synovial infiltrating lymphocytes from RA patients and in the synoviocytes from PVS patients, whereas the enzyme activity was expressed at a low-to-borderline level in the PBL and synovial lymphocytes from OA, PVS, and trauma patients and was absent in the synoviocytes from RA as well as OA and trauma patients. In RA patients, the telomerase activity level in synovial infiltrating lymphocytes was significantly correlated with the intensity of synovial lining hyperplasia, microvessel proliferation, lymphocyte infiltration, and percentage of synovial cells positive for proliferating cell nuclear antigen in rheumatoid synovium. CONCLUSION: Telomerase activation in lymphocytes may provide insights into the progression of synovitis and synovial proliferation in RA. Moreover, the enzyme may be implicated in the proliferation of synoviocytes in PVS.
9667620 The effects of menopausal status and disease activity on biochemical markers of bone metab 1998 Jun The effects of menopause and disease activity on bone metabolism in rheumatoid arthritis (RA) were studied by using biochemical markers of bone metabolism. We measured osteocalcin, bone-specific alkaline phosphatase, urinary total pyridinoline and deoxypyridinoline, and urinary free deoxypyridinoline in 78 female patients with RA (39 pre-menopause, Pre-RA; 39 post-menopause, Post-RA) and 54 female normal controls (28 pre-menopause, Pre-NC; 26 post-menopause, Post-NC). In Pre-RA, although bone formation was equal to Pre-NC, bone resorption increased. In Post-RA, however, bone formation was lower while bone resorption was higher than in Post-NC. The high disease activity RA group showed higher bone turnover than the low disease activity RA group. We conclude that menopause affects the bone turnover in RA as well as in normal controls. In Pre-RA, osteopenia is caused by the increase in bone resorption. In Post-RA, osteopenia is caused by the increase in uncoupling between bone formation and bone resorption. Furthermore, the high disease activity of RA induces high bone turnover.
9175936 Increased serum NG-hydroxy-L-arginine in patients with rheumatoid arthritis and systemic l 1997 May OBJECTIVES: To determine the feasibility of monitoring the serum concentration of NG-hydroxy-L-arginine (L-NHA) as an index of an increased nitric oxide (NO) synthase activity in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) compared with nitrate (NO3-), the major circulating metabolite of NO whose concentration is influenced by dietary intake. METHODS: The serum concentrations of L-NHA, L-arginine (L-Arg), and NO3- were determined in 33 patients with RA, 25 patients with SLE and, 29 healthy subjects. RESULTS: Serum L-NHA was significantly increased in RA patients with high disease activity (287% of control, p < 0.01), but not with low disease activity (115%), as well as in patients with SLE (173%, p < 0.01). In contrast, serum NO3- did not differ significantly between either group of patients and the respective control group. CONCLUSION: NO synthase activity or expression, or both, is upregulated in RA patients with high disease activity and in patients with SLE. Serum L-NHA seems to be a more specific and reliable index of an increased activity of this enzyme in patients with acute or chronic inflammatory diseases than NO3-.
11367869 Antioxidants as adjuvant therapy in rheumatoid disease. A preliminary study. 2001 The aim of the present study was to assess the therapeutic value of adding a high dose of vitamin E or an antioxidant combination to the treatment regimen of the rheumatoid disease. The study was carried out on 30 patients with rheumatoid disease diagnosed according to the criteria of American Rheumatism Association (ARA), subvided into three equal groups. Patients in group I received a standard treatment of intramuscular methotrexate (CAS 59-05-2; 12.5 mg/week), oral sulphasalazine (CAS 599-79-1; 0.5 g b.i.d.) and indometacin (CAS 53-86-1; 100 mg suppository at bed-time). In group II the patients received the standard treatment plus a combination of antioxidants. Patients in group III received a high dose of vitamin E (400 mg t.i.d.) in addition to the standard treatment. The disease state was evaluated using Ritchle's articular score index and the duration of morning stiffness. Laboratory evaluations included the rheumatoid factor, erythrocyte sedimentation rate (ESR), plasma levels of vitamin E and malonedialdehyde (MDA), and the activity of glutathione peroxidase (GPx). In the group receiving the standard regimen, the patients started to feel tangible improvement by the end of the second month. With adjuvant therapy of either the antioxidant combination or a high dose of vitamin E the symptoms of arthritis were better controlled from the first month. By the end of the second month, the values of the three monitoring tests were significantly decreased indicating better control of the disease. The percentage increase in the activity of GPx was highest in patients taking the antioxidant combination and least in those taking the standard treatment. The decrease in plasma MDA followed the same pattern. With adjuvant therapy, the vitamin E level in plasma increased with the duration of treatment. The results obtained in the present study are encouraging. The clinical improvement and the shift in the disease indices towards normal make the use of antioxidants as adjuvant therapy in rheumatoid disease worth pursuing.