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ID PMID Title PublicationDate abstract
15616917 [A case of severe gangrenous ischemic colitis following nonsteroidal anti-inflammatory dru 2004 Dec A 48-year-old woman presented with bloody diarrhea, exsiccosis, abdominal pain and fever. A CT-scan showed air inclusions and thickening of the colonic wall. Laparotomy revealed partial necrosis of the colonic wall from the cecum to the rectosigmoid junction. After colectomy with ileorectostomy recovery was uneventful. The histological examination showed erosions, ulcerations, necrosis and some abscesses along the colonic wall which were not typical for ulcerative colitis or Crohn's disease. The patient reported medication with diclofenac for rheumatoid arthritis. The most probable diagnosis was NSAID-induced colitis. That NSAID may cause colitis has often been described in literature, but there have been only few records on nearly total colon necrosis.
15324932 Influence of arginine deimination on antigenicity of fibrinogen. 2004 Sep Autoreactivity is controlled at various steps by numerous mechanisms and is a key to understanding and treating autoimmune disease. Recently, an antibody against deiminated fibrinogen (DI-FBG) was detected in patients with rheumatoid arthritis (RA) with high specificity and sensitivity. DI-FBG converted enzymically by peptidyl arginine deiminase, was also detected in synovial membrane. In the present study, we investigated whether antibody to DI-FBG is produced in mice immunized with DI-FBG. Mice were immunized with DI-FBG in the presence or absence of adjuvant. Production of the specific antibody was only induced with adjuvant. The resulting antibody was specific for DI-FBG and did not react with intact/native fibrinogen. Furthermore, it recognized deiminated human fibrinogen and cyclic citrullinated peptide (CCP). These results suggested that mouse fibrinogen acquires antigenicity in mice through deimination and therefore, autoantibody such as that detected in RA patients specifically may be induced.
15110231 Synovial fluid estrogens in rheumatoid arthritis. 2004 Mar Experimental and clinical evidence suggest that immune reactivity is modulated by gender. Immune reactivity is greater in females than in males and lymphocytes and monocytes from female subjects shows higher antigen presenting activity and mitogenic responses. Steroid hormones can be converted along defined pathways to downstream hormones in the periphery. The conversion of dehydroepiandrosterone (DHEA) in target macrophages leads to an increase of downstream effector hormones (including estrogens), which may be an important factor for local immunomodulation at least in RA synovitis. The presence in the RA synovial fluids (SF) of an altered sex hormone balance resulting in lower immunosuppressive androgens and higher immunoenhancing estrogens, might determine a favorable condition for the development of the immuno-mediated RA synovitis and synovial hyperplasia. The increased estrogen concentration observed in RA SF of both sexes are characterized by the hydroxylated forms, in particular 16alpha-hydroxyestrone, that is a mitogenic and proliferative endogenous hormone. In contrast to 16alpha-hydroxylated estrogens, the 2-hydroxylated forms inhibit growth promoting effects of E2 and were found low in RA SF. Therefore, dose-related conversion to pro- or anti-inflammatory downstream metabolites of estrogens might support the dual role of estrogens (pro or anti-inflammatory) for example during estrogen replacement therapy, depending on local concentration (i.e. SF in RA) of 16alpha-hydroxyestrone or 2-hydroxyestrogens.
12415583 A single dose, placebo controlled study of the fully human anti-tumor necrosis factor-alph 2002 Nov OBJECTIVE: To assess the pharmacokinetics, safety profile, and efficacy of the fully human anti-tumor necrosis factor-alpha (anti-TNF-alpha) monoclonal antibody adalimumab (D2E7) in patients with long-standing, active rheumatoid arthritis (RA). METHODS: This was a randomized, double blind, placebo controlled study of single intravenous injections of ascending doses (0.5 to 10 mg/kg) of adalimumab in 5 cohorts of 24 patients each (18 adalimumab and 6 placebo in all cohorts except the 0.5 mg/kg cohort of 17 adalimumab, 7 placebo). A total of 120 patients participated (adalimumab 89, placebo 31). The clinical response was measured by changes in composite scores defined by the criteria of the European League Against Rheumatism (EULAR) and the American College of Rheumatology. RESULTS: Single doses of adalimumab showed a rapid onset of clinical effect (24 hours to 1 week), with peak efficacy at 1 to 2 weeks that was sustained for at least 4 weeks and for as long as 3 months in some patients. EULAR response was seen at least once during the 4 week period after drug injection in 29% of patients in the placebo group as well as in 41%, 78%, 72%, 89%, and 100% in the 0.5, 1, 3, 5, and 10 mg/kg groups, respectively. No dose related increases in adverse events were observed in the adalimumab patients compared with the placebo group. Adalimumab systemic drug exposure (AUC0-( )) increased linearly with an increase in dose. The mean total serum clearance was 0.012 to 0.017 l/h, and the steady-state volume of distribution ranged from 4.7 to 5.5 l. The estimated mean terminal half-life ranged from 10.0 to 13.6 days for the 5 cohorts, with an overall mean half-life of 12 days. CONCLUSION: Treatment with the fully human Mab adalimumab was safe and well tolerated when administered as a single intravenous injection at doses up to 10 mg/kg, and was associated with a clinically significant improvement in the signs and symptoms of active RA.
15593217 Expression of toll-like receptors 2 and 4 in rheumatoid synovial tissue and regulation by 2004 Dec OBJECTIVE: To study the expression of Toll-like receptor 2 (TLR-2) and TLR-4 and its association with proinflammatory cytokines in synovial tissue from patients with rheumatoid arthritis (RA), osteoarthritis (OA), and healthy individuals. METHODS: Synovial tissue specimens from 29 RA patients were stained for TLR-2, TLR-4, and proinflammatory cytokines (interleukin-1beta [IL-1beta], IL-12, IL-17, IL-18, and tumor necrosis factor alpha [TNFalpha]). The expression of TLR-2, TLR-4, and cytokines as well as the degree of inflammation in synovial tissue were compared between patients with RA, patients with OA (n = 5), and healthy individuals (n = 3). Peripheral blood mononuclear cells (PBMCs) were incubated with IL-12 and IL-18, and TLR expression was assessed using fluorescence-activated cell sorter analysis. Production of TNFalpha and IL-6 was measured using Luminex bead array technology. RESULTS: In RA synovial tissue, the expression of TLR-2 was slightly higher than that of TLR-4. Interestingly, both TLR-2 and TLR-4 were expressed at higher levels in moderately inflamed synovium, as compared with synovial tissue with no or severe inflammation. TLR expression in both the lining and the sublining was associated with the presence of IL-12 and IL-18, but no other cytokines, in the lining. The expression of both TLRs was low in synovial tissue from OA patients and healthy donors. Stimulation of PBMCs with IL-12 and IL-18 resulted in increased expression of both TLR-2 and TLR-4; this could be blocked with anti-interferon-gamma (anti-IFNgamma) antibodies, suggesting a role for IFNgamma. Lipopolysaccharide- or lipoteichoic acid-mediated triggering of PBMCs incubated with IL-12/IL-18 or IFNgamma led to an increased production of both TNFalpha and IL-6, indicating the functionality of TLR-2 and TLR-4. CONCLUSION: TLR-2 and TLR-4 are expressed in synovial tissue of patients with clinically active disease and are associated with the levels of both IL-12 and IL-18. The synergistic effect of IL-12 and IL-18 on T cell IFNgamma production seems to regulate expression of TLR-2 and TLR-4 in the synovial tissue of RA patients.
15053452 A short history of data banking in the United States from 1974 to 2003. 2004 Mar There have been 4 major longitudinal data banking efforts within the United States: ARAMIS, the Western Consortium, and the individual data banks of Drs. Ted Pincus and Fred Wolfe. ARAMIS began in the 1970s, and helped to develop the language and methodology of rheumatology data banks using biannual surveys. The National Data Bank for Rheumatic Diseases used the ARAMIS model beginning in the late 1990s to form a very large contemporary rheumatology data bank. Hybrid models using both survey data and clinical data were put into practice by Pincus and Wolfe, and by Paulus at the Western Consortium.
15184092 Social support and psychological adjustment among Latinas with arthritis: a test of a theo 2004 Jun BACKGROUND: Among people coping with chronic illness, tangible social support sometimes has unintended negative consequences on the recipient's psychological health. Identity processes may help explain these effects. Individuals derive self-worth and a sense of competence by enacting social roles that are central to the self-concept. PURPOSE: This study tested a model drawing from some of these theoretical propositions. The central hypothesis was that tangible support in fulfilling a highly valued role undermines self-esteem and a sense of self-efficacy, which, in turn, affect psychological adjustment. METHODS: Structured interviews were conducted with 98 Latina women with arthritis who rated the homemaker identity as being of central importance to the self-concept. RESULTS: A path analysis indicated that, contrary to predictions, tangible housework support was related to less psychological distress. Emotional support predicted greater psychological well-being. These relationships were not mediated by self-esteem or self-efficacy. Qualitative data revealed that half of the sample expressed either ambivalent or negative feelings about receiving housework support. CONCLUSIONS: Results may reflect social and cultural norms concerning the types of support that are helpful and appropriate from specific support providers. Future research should consider the cultural meaning and normative context of the support transaction. This study contributes to scarce literatures on the mechanisms that mediate the relationship between social support and adjustment, as well as illness and psychosocial adaptation among Latina women with chronic illness.
14994396 Erectile dysfunction associated with scleroderma: a case-control study of men with sclerod 2004 Mar OBJECTIVE: To determine if men with systemic sclerosis (SSc) are at increased risk of developing erectile dysfunction (ED) compared to men with rheumatoid arthritis (RA), and to investigate the temporal relationship of ED related to rheumatologic disease. METHODS: Men with SSc identified from the practices of 2 rheumatologists were age matched to men with RA and were sent a standardized, validated questionnaire (SHIM IIEF-5) to assess ED and related factors. The questionnaire also addressed information on the subject's overall health and rheumatic disease status. RESULTS: The response rate was 50% (48% in SSc and 55% in RA), thus 43 with SSc and 23 with RA were included. The mean age of respondents was 53 yrs +/- 1.34 (SEM), (range 34 to 83). No statistical differences were found for marital status, alcohol or drug use, or past/present smoking. Men with scleroderma weighed less than men with RA (p < 0.004) and were more likely to have Raynaud's phenomenon (p < 0.0001), and to have fewer biological children (2.0 +/- 0.2 vs 2.7 +/- 0.2, p < 0.01). The prevalence of erectile dysfunction was 81% (SSc) and 48% (RA), (relative risk for SSc vs RA: 4.77; 95% CI: 1.55, 14.66; p < 0.005). In subjects who had ED, 78% (both SSc and RA) reported it occurring after disease onset. Men with SSc noted their ED began 2.7 +/- 1.2 (mean +/- SEM) years after their disease was diagnosed, and similarly, men with RA noted their ED began 3.3 +/- 2.2 years after disease diagnosis, p = 0.82. Eighty-six percent of patients with SSc had Raynaud's phenomenon (RP) compared to 19% RA, p < 0.0001. Eighty percent of subjects with RP (SSc + RA) had ED versus 50% of men without RP, p < 0.01. In RA subjects with RP (n = 4), 75% had experienced ED, versus 39% of RA without RP, p = 0.18. Possible confounding factors for ED were examined including smoking, hypertension, diabetes, and steroid use; all except self-reported history of nerve damage (p < 0.0005) and diabetes (p < 0.02) were insignificant for predicting the likelihood of increased ED. Patients with SSc were not more likely than RA to have experienced nerve damage (p = 0.25), or diabetes (p = 0.19). CONCLUSION: ED occurs frequently in SSc, is more common than in RA, and occurs on average 3 years after disease onset. RP appears to be associated with ED in both SSc and RA, but is not necessarily an independent risk factor for ED in SSc alone.
12115223 Presence of autoantibodies to the glycolytic enzyme alpha-enolase in sera from patients wi 2002 May OBJECTIVE: To identify a new autoantigen/autoantibody population in rheumatoid arthritis (RA) sera. METHODS: Following a population-based recruitment effort, 255 patients with very early arthritis (median disease duration 4 months) were studied using different clinical, biologic, and radiologic assessments. After a followup period of 1 year, patients were classified as having RA (n = 145), non-RA rheumatic diseases (n = 70), and undifferentiated arthritis (n = 40). Patients' sera were analyzed by one-dimensional (1D) and 2D Western blotting. The recognized 50-kd protein was analyzed by matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry (MS). RA serum reactivities were evaluated against the recombinant protein synthesized by an in vitro coupled transcription-translation system. RESULTS: On 1D Western blots, 36 of the 145 RA sera bound to a 50-kd polypeptide. On 2D Western blots, anti-50-kd+ RA sera recognized a triplet of isoelectric point 6.5-7.0 and a molecular mass of 50 kd. The 3 spots of the triplet were analyzed by MALDI-TOF MS and were shown to correspond to human alpha-enolase. A goat anti-enolase antiserum, which recognized a band comigrating with the 50-kd antigen on 1D Western blots, gave a labeling pattern on 2D Western blots similar to that observed with anti-50-kd+ RA sera. Among the 36 RA sera that identified alpha-enolase in protein maps, only 8 recognized the recombinant (unmodified) alpha-enolase. The specificity of anti-alpha -enolase antibodies for RA was 97.1%. Half of the anti-alpha -enolase-positive RA patients were negative for both rheumatoid factor and antifilaggrin antibodies. The presence of anti-alpha-enolase antibodies was the greatest predictive factor of radiologic progression in the first 66 RA patients included. CONCLUSION: Autoantibodies to alpha-enolase, an enzyme of the glycolytic pathway, are present in the sera of patients with very early RA and have potential diagnostic and prognostic value for RA.
12379632 Bone destruction in arthritis. 2002 Nov Rheumatoid arthritis (RA) is characterised by the presence of an inflammatory synovitis accompanied by destruction of joint cartilage and bone. Destruction of cartilage matrix results predominantly from the action of connective tissue proteinases released by RA synovial tissues, chondrocytes, and pannus tissue. Several lines of evidence in RA and in animal models of arthritis support a role for osteoclasts in the pathogenesis of bone erosions. RA synovial tissues produce a variety of cytokines and growth factors that may increase osteoclast formation, activity, and/or survival. These include interleukin 1alpha (IL1alpha) and beta, tumour necrosis factor alpha (TNFalpha), IL11, IL17, and macrophage colony stimulating factor (M-CSF). Receptor activator of NFkappaB ligand (RANKL) is an essential factor for osteoclast differentiation and also functions to augment T cell-dendritic cell cooperative interactions. CD4+ T cells and synovial fibroblasts derived from RA synovium are sources of RANKL. Furthermore, in collagen induced arthritis (CIA), blockade with osteoprotegerin (OPG), a decoy receptor for RANKL, results in protection from bone destruction. To further evaluate the role of osteoclasts in focal bone erosion in arthritis, arthritis was generated in the RANKL knockout mouse using a serum transfer model. Despite ongoing inflammation, the degree of bone erosion in arthritic RANKL knockout mice, as assessed by microcomputed tomography and correlated histopathological analysis, was dramatically reduced compared with that seen in arthritic control mice. Cartilage damage was present in both the arthritic RANKL knockout mice and in arthritic control littermates, with a trend toward milder cartilage damage in the RANKL knockout mice. This study supports the hypothesis that osteoclasts play an important part in the pathogenesis of focal bone erosion in arthritis, and reveals distinct mechanisms of cartilage destruction and bone erosion in this animal model of arthritis. Future directions for research in this area include the further investigation of a possible direct role for the RANKL/RANK/OPG system in cartilage metabolism, and the possible role of other cell types and cytokines in bone erosion in arthritis.
14561184 TNFalpha as therapeutic target: new drugs, more applications. 2002 Dec TNFalpha is a crucial cytokine in the establishment and maintenance of inflammation in multiple autoimmune diseases. With the introduction of infliximab and etanercept, two injectable biologic TNFalpha blocking drugs are now available. Both are effective in the treatment of rheumatoid arthritis, reducing clinical inflammation and damage to bones. In addition, infliximab is FDA-approved for the treatment of Crohn's disease. More recent controlled trials have shown effectiveness for TNFalpha blockers in psoriasis, psoriatic arthritis, and ankylosing spondylitis. Further trials are underway in diverse inflammatory conditions including including uveitis, sarcoidosis, Behcet's syndrome, and graft versus host disease. Although the safety profile has been generally excellent, the rare development of reactivation tuberculosis, anti double-stranded DNA antibodies, or a demyelination syndrome point out the need for further close follow-up of treated patients. New formulations of recombinant anti-TNFalpha biologics undergoing clinical trials use modifications to reduce antigenicity, increase the half-life, and maintain or extend the efficacy of these agents. Future development of TNFalpha antagonists is turning to small molecule inhibitors. The inhibition of the TNFalpha signaling cascade is under study using blockers of the p38, JNK, and ERK kinases, and by antagonists of transcription factor NF-kappaB activation. The goal of this approach is to develop compounds that are orally available, have increased selectivity compared to generalized blockade of TNFalpha, yet are therapeutically useful for a range of chronic inflammatory diseases.
12653851 High serum vascular endothelial growth factor correlates with disease activity of spondyla 2003 Apr Angiogenesis is involved in chronic inflammatory joint diseases such as rheumatoid arthritis (RA). Vascular endothelial growth factor (VEGF) plays a crucial role in angiogenesis. The spondylarthropathies (SpA) are characterized by enthesitis and synovitis, in which blood vessels participate. The objective of this study was to investigate serum VEGF levels and their potential associations with disease activity markers for SpA. Sera were collected from 105 patients with SpA (72 with ankylosing spondylitis (AS), four with psoriatic arthritis (PsA), six with reactive arthritis (ReA), eight with enteropathic arthropathy and 15 with undifferentiated SpA), 50 patients with rheumatoid arthritis (RA) and 64 healthy controls. Disease activity in SpA patients was assessed using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and laboratory parameters of inflammation [erythrocyte sedimentation rate (ESR) and C-reactive protein level (CRP)]. Serum VEGF levels were significantly higher in SpA patients (316.4 +/- 215.6 pg/ml) and RA patients (405.2 +/- 366.5) than in controls (217.3 +/- 145.2) (P = 0.003). In SpA patients, serum VEGF levels correlated with disease activity indices (BASDAI: r = 0.22, P = 0.04; ESR: r = 0.3, P = 0.003; and CRP: r = 0.23, P = 0.02). Serum VEGF levels were not associated with presence of extra-articular manifestations or syndesmophytes or with the grade of sacroiliitis. These results suggest that VEGF and therefore angiogenesis may play a role in SpA pathogenesis and may serve as a disease activity marker in SpAs.
12029513 Patella resurfacing: no benefit for the long-term outcome of total knee arthroplasty. A 10 2002 May A follow-up of more than 10 years among patients who have undergone a total knee arthroplasty (TKA) was performed to determine the significance of patella resurfacing for the long-term outcome. The clinical outcome was assessed by the Knee Society Score (KSS), and the radiological outcome was determined based on the Knee Society Roentgenographic Evaluation System. The patella was preserved in 21 knees and resurfaced in 44 knees. The mean follow-up time was 11.6 years (range 10-16.3 years). There was no significant difference in the clinical outcome between the knees with patella resurfacing (knee points: mean 85.3 +/-12.9, function points: mean 70.3 +/- 23.4) and the knees with patella retention (knee points: mean 82.7 +/- 16.2, function points: mean 71.7 +/- 22.4; p = 0.58 for knee, and p = 0.83 for function points). There was also no significant difference in the radiological outcomes regarding the angles alpha, beta, Upsilon, delta, and valgus ( p > 0.05 for each variable). There was, however, a trend towards more lucencies in TKAs with a resurfaced patella on the tibia side in the anteroposterior view ( p = 0.052). Patellar complications were found more often in the resurfaced group (20.5%) than in the group without resurfacing (9.6%). The results indicate overall no advantage of patella resurfacing compared with patella retention in the long run.
12510367 [Etanercept]. 2002 Dec Etanercept is a protein comprised of the extracellular domains of two TNF receptors attached to a Fc portion of an IgG. Etanercept was approved for not only reducing signs and symptoms but inhibiting of structural damage in patients with active RA who had an inadequate response to one or more DMARDs. Moreover, combination therapy with methotrexate will be attractive for severely active patients. The proportion of patients who have discontinued therapy due to adverse events is approximately 4%. Etanercept has not raised the risk for serious infections(0.04/patient-year) as well as malignancies. There are sporadic case reports of aplastic anemia, demyelination, lupus-like conditions, which are not significant so far. Etanercept may contribute rheumatologists to manage patients with RA.
12384914 Cachexia in rheumatoid arthritis is not explained by decreased growth hormone secretion. 2002 Oct OBJECTIVE: Patients with rheumatoid arthritis (RA) lose body cell mass (BCM) by unknown mechanisms. Since the loss of BCM in normal aging individuals parallels the characteristic age-related decline in growth hormone (GH) secretion, this study was carried out to determine whether further decreased GH secretion plays a role in the pathogenesis of this loss of BCM in RA patients, termed "rheumatoid cachexia." METHODS: GH secretory kinetics were determined by deconvolution analysis in 16 patients with RA and 17 healthy controls matched for age (mean +/- SD 45.4 +/- 13.2 years and 47.1 +/- 14.6 years, respectively), sex, race, and body mass index. Blood samples were obtained every 20 minutes for 24 hours. Body composition was ascertained using total-body potassium (TBK) as a measure of BCM and dual x-ray absorptiometry to determine fat mass. RESULTS: BCM was reduced in patients with RA compared with healthy controls (mean +/- SD gm TBK 79.5 +/- 9.5 versus 94.9 +/- 11.9; P < 0.0005), but there was no difference in fat mass. GH kinetic parameters in patients with RA did not differ from those in controls. CONCLUSION: These findings suggest that GH kinetics are unaltered in RA patients compared with healthy subjects; thus, GH deficiency does not account for rheumatoid cachexia.
12225387 Dendritic cells, chemokine receptors and autoimmune inflammatory diseases. 2002 Oct Dendritic cells (DC) have been implicated in the induction of autoimmune diseases and have been identified in lesions associated with several autoimmune inflammatory diseases. Since DC are regarded as the professional antigen-presenting cell (APC) of the immune system and the only APC capable of activating naïve T cells, they are likely to play a significant role in breaking tolerance of self-reactive lymphocytes and in supporting autoimmune responses in these diseases. A number of studies have revealed that small molecular weight chemotactic proteins known as chemokines are present within the autoimmune lesions and may contribute to the recruitment not only of DC populations, but also of immune cells such as T cells, B cells, neutrophils and monocytes into the site, and to the formation of organized lymphoid tissue structures within the target organ. The focus of this review will be a discussion of the role of chemokines in the recruitment of DC in human autoimmune inflammatory disorders, specifically the trafficking of DC into the inflammatory sites and the subsequent migration of differentiated DC from the inflammatory sites into the draining lymph nodes. Once DC are properly positioned within the lymph nodes, circulating antigen specific naïve T cells can interact with DC and become activated, clonally expanded and stimulated to undergo differentiation into antigen-experienced memory T cells. Subsequent reactivation of memory T cells that enter the autoimmune lesions by DC present in the inflammatory lesion is thought to play a central role in tissue inflammation.
14695655 Plasma lipid peroxidation and antioxidant levels in patients with rheumatoid arthritis. 2004 Jan In recent years, a great number of studies have investigated the possible role of reactive oxygen species in the aetiology and pathogenesis of rheumatoid arthritis (RA). The aim of this study was to investigate plasma concentrations of vitamin E, beta-carotene, activities of glutathione peroxidase (GSH-Px) and catalase, levels of lipid peroxidation (MDA) and reduced glutathione (GSH) in 36 patients with rheumatoid arthritis (RA) and 22 healthy age-matched controls. The plasma activity of GSH-Px and catalase (p < 0.001), levels of GSH (p < 0.01), concentration of beta-carotene (p < 0.05) and vitamin E (p < 0.001), haemoglobin and hematocrit (p < 0.05) were significantly lower in patients with RA than in controls. The MDA levels (p < 0.01), C reactive protein, rheumatoid factor, anti-streptolysin-o values (p < 0.001), platelet count (p < 0.05) and erythrocyte sedimentation rate (p < 0.001) were higher in the patient group than in the control group. These results provide some evidence for a potential role of increased lipid peroxidation and decreased enzymic and non-enzymic antioxidants in RA by its inflammatory character. These results suggested that oxidant stress plays a very important role in the pathogenesis of RA.
16366142 Clinical relevance of antikeratin antibodies in rheumatoid arthritis and symmetric polyart 2004 Chronic hepatitis C virus (HCV) has been linked to extrahepatic autoimmune phenomena. In addition a variety of autoantibodies were found in patients with HCV. This study was performed to assesss the clinical relevance of antikeratin antibodies in rheumatoid arthritis (RA) and in patients with symmetric polyarthritis associated with hepatitis C infection. Serum antikeratin antibodies were evaluated in 3 different groups of patients; all were rheumatoid factor (RF) seropositive: Group 1: 31 patients with HCV associated symmetric polyarthralgia or arthritis. Group 2: 28 patients with RA (modified ACR criteria for probable RA). Group 3: 16 patients with autoimmune disorders other than RA. Seventeen healthy individuals matched for age and sex served as controls. In our study, 75 patients who were rheumatoid factor positive (measured by ELISA, the cutoff was established to 20 U/mL) were tested for antikeratin antibodies using an indirect immunofluorescence technique with 1:10 serum dilution. Antikeratin antibodies were detected in 18/28 (64%) patients with true RA and only 3/31 (9%) patients with HCV-related arthritis (p < 0.0001). Antikeratin antibodies were observed in 3/16 (18%) patients of group 3 (p < 0.05). Antikeratin antibodies were not found in the sera of the healthy controls.
12672184 Intravenous human recombinant tumor necrosis factor receptor p55-Fc IgG1 fusion protein Ro 2003 Apr OBJECTIVE: To determine the optimal dose regimen for intravenous Ro 45-2081 (lenercept) in patients with rheumatoid arthritis (RA) by evaluating efficacy, safety, tolerability, and pharmacokinetic and pharmacodynamic characteristics. METHODS: Adult patients with longstanding RA who were taking stable doses of nonsteroidal antiinflammatory drug and/or low dose corticosteroids but who had stopped their previous disease-modifying antirheumatic drug were randomly assigned to receive 3 intravenous infusions, one every 4 weeks, of placebo or Ro 45-2081 in a double blind, placebo controlled, parallel group multicenter trial. Patients received one of the following: (1) placebo, (2) low dose Ro 45-2081 (0.05 mg/kg, maximum 5 mg), (3) middle dose (mid-dose) Ro 45-2081 (0.2 mg/kg, maximum 20 mg), or (4) high dose Ro 45-2081 (0.5 mg/kg, maximum 50 mg). Efficacy measures included change from baseline in number of swollen joints and tender joints, scores on physician and patient assessments of disease activity, and patient assessment of pain, as well as acute phase reactants. RESULTS: Patients treated with Ro 45-2081 exhibited improvement after one day of the first intravenous infusion. This treatment benefit maximized by 2 weeks but diminished thereafter. After the second and third infusion, improvement was of shorter duration as non-neutralizing anti-Ro 45-2081 antibodies developed and accelerated clearance of Ro 45-2081. There were no antibodies after the first infusion. This made efficacy transient in the mid-dose group and modest in the low and high dose groups at 12 weeks of treatment, resulting in no statistical differences at most time points or doses of Ro 45-2081. The majority of adverse experiences were mild or moderate, and were not related or only remotely related to study drug. No clinically relevant changes in mean laboratory values were reported. The third dose pharmacokinetic measurements showed that the average Ro 45-2081 clearance rate more than doubled compared with the first dosing interval, thus reducing the average Ro 45-2081 AUC by 36%. CONCLUSION: Intravenous Ro 45-2081 every 4 weeks proved to be well tolerated and transiently effective in the mid-dose group and modestly effective in the low and high dose groups in patients with longstanding RA. The interactions between Ro 45-2081, its non-neutralizing anti-Ro 45-2081 antibody, and the clinical benefit remain complex, but affected efficacy over the 12 weeks of treatment as Ro 45-2081 concentrations fell.
12652686 [Clinical significance of MMP-3 in patients with rheumatoid arthritis: comparison with oth 2003 Jan We determined serum metalloproteinase-3(MMP-3) and inflammatory cytokine(IL-6, IL-8) levels in patients with rheumatoid arthritis(RA). Sera were obtained from 307 healthy subjects(female 140, male 167), 54 RA patients, and 17 osteoarthritis (OA). The MMP-3 concentrations in healthy female and male were 43.3 +/- 15.3 ng/ml and 90.7 +/- 26.0 ng/ml, respectively. The serum MMP-3 levels in male were significantly higher than those in female (p < 0.0001). MMP-3 levels in RA patients(259.1 +/- 34.2 ng/ml) were significantly higher than OA(43.6 +/- 6.1 ng/ml) or healthy controls. There was a significant correlation between MMP-3 and CRP(r = 0.586), IL-6(r = 0.345) levels in serum. In contrast, no significant correlation was observed between MMP-3 and IL-8(r = 0.19), or CA-RF(r = 0.052) levels. However, there were some cases with high MMP-3 levels in CA-RF-negative patients definitely diagnosed as RA. These findings suggest that MMP-3 determination is useful for the early diagnosis and the follow-up during the treatment for RA patients.