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ID PMID Title PublicationDate abstract
20039430 Functional autoantibodies against serpin E2 in rheumatoid arthritis. 2010 Jan OBJECTIVE: To search for novel autoantibodies in patients with rheumatoid arthritis (RA) in an effort to better understand the processes of joint destruction in this disease. METHODS: Using a modified SEREX technique and complementary DNA derived from RA synovium, serpin E2 was identified as a novel autoantigen and was analyzed by immunohistochemistry. Levels of anti-serpin E2 autoantibodies in serum and synovial fluid from patients with RA, osteoarthritis (OA), psoriatic arthritis, and ankylosing spondylitis, and/or from healthy individuals were assessed by enzyme-linked immunosorbent assay. Since serpin E2 is an inhibitor of serine proteases, we studied the inhibitory activity of serpin E2 toward its target, urokinase plasminogen activator (uPA), in vitro in the presence of isolated anti-serpin E2 autoantibodies and in vivo using the uPA activity assay. RESULTS: We identified autoantibodies against serpin E2 by the SEREX technique. Serpin E2 was overexpressed in RA synovial tissues as compared with OA synovial tissues. Significantly higher levels of anti-serpin E2 autoantibodies were present in samples of synovial fluid (28%) and serum (22%) from RA patients as compared with OA patients (0 and 6%, respectively) or with healthy individuals (6% of sera). Most importantly, anti-serpin E2 autoantibodies isolated from RA sera reversed the inhibitory activity of serpin E2 by 70%. Furthermore, the levels of anti-serpin E2 autoantibodies correlated with the uPA activity in vivo. CONCLUSION: This study characterizes a functional property of a novel autoantibody in RA. Since anti-serpin E2 autoantibodies interfere with the inhibitory activity of serpin E2 toward serine proteases, they might facilitate the joint destruction in RA.
20158371 Validation of the International Classification of Functioning Disability and Health framew 2010 PURPOSE: To examine the construct validity of the International Classification of Functioning Disability and Health (ICF) framework using multidimensional item response modelling and data collected in different regions from patients with five chronic health conditions. We assume that the ICF components should represent statistically called dimensions that are distinct although related. METHOD: Retrospective validation study using the ICF Core Sets from a convenience sample of patients in an international multicentre, cross-sectional database obtained in different rehabilitation centres. Health professionals working in 89 rehabilitation centres in 32 countries collected data from 3227 rehabilitation patients using the respective ICF Core Sets. Patients included had one of the following health conditions: low back pain (LBP), rheumatoid arthritis (RA), osteoarthritis (OA), obesity (OB) or post-stroke. Data from questions regarding a patient's functioning based on body structures and functions, activities, participation along the ICF Core Sets were analysed with multidimensional item response modelling. RESULTS: The multidimensional models fit the data better than a model with few or no specifications regarding an underlying framework. For example, a model separating four dimensions 'body structures', 'body functions', 'activities' and 'participation' fits the data better than a model differentiating between 'body functions and structures' and 'activities and participation'. The ICF framework with its components represents underlying statistically called dimensions. CONCLUSION: The results of this study support the construct validity of the functioning part of the ICF. The distinct dimensions may facilitate the alignment of ICF components with other measures used clinically and in research. Based on our results it is justifiable to construct instruments integrating ICF categories within components.
20652775 Comparative effectiveness of rheumatoid arthritis therapies. 2010 Oct Physicians and patients must choose between several therapeutic interventions for rheumatoid arthritis and need to compare the available therapeutic options. Although randomized, placebo-controlled trials are essential to establish the efficacy of a new treatment, they are not much help when it comes to selecting the best therapy for an individual patient. Comparative effectiveness research (CER) is set to provide direct comparisons between therapeutic strategies. CER attempts to weigh the benefits against the potential harms of a particular intervention. Furthermore, CER may help identify specific patient subgroups that are more likely to benefit from a particular therapy or at increased risk of adverse events. Several study designs are available for CER, including pragmatic trials, indirect comparisons using meta-analysis, and observational studies. Understanding the strengths and weaknesses of each design improves the interpretation of the results. In this article, I illustrate CER principles using examples from the literature on biologic antirheumatic agents.
20582408 Induced apoptosis of chondrocytes by Porphyromonas gingivalis as a possible pathway for ca 2010 Oct The role of bacterial infections in the pathogenesis of rheumatoid arthritis (RA) has gained increasing interest. Patients with RA often exhibit periodontal disease, which is associated with pathogens like Porphyromonas gingivalis. The present study examines the direct effects of P. gingivalis on apoptosis of human chondrocytes (a feature of inflammatory joint diseases) as one can assume an interrelation of pathogenesis of RA and P. gingivalis infections. Primary chondrocytes were infected with P. gingivalis. Early apoptotic and dead cell analysis was performed using Annexin-V, 7AAD, and propidium iodide and examined by flow cytometry and fluorescence microscopy. Caspase activation and DNA fragmentation were determined by western blot analysis and TUNEL reaction. Flow cytometry and fluorescence microscopy demonstrated an increase of Annexin-V-positive early apoptotic chondrocytes after infection. Western blot showed upregulation of activated caspase-3 expression, and TUNEL reaction revealed considerable DNA fragmentation following infection. The data show that P. gingivalis promotes early and later stages of apoptosis of primary human chondrocytes, which might contribute to the joint damage seen in the pathogenesis of RA.
19506586 Management of RA medications in pregnant patients. 2009 Jul A desire for children or the presence of pregnancy limits the drug therapy options for a woman with rheumatoid arthritis. Combination therapies that include methotrexate or new drugs that have not been studied or used in pregnant patients must be excluded, even though they might be highly efficacious. With few exceptions, the reason for this exclusion is not the proven teratogenicity of the drugs, but the absence of proven safety for the fetus. Whereas methotrexate, leflunomide, abatacept and rituximab must be withdrawn before a planned pregnancy, tumor necrosis factor inhibitors and bisphosphonates can be continued until conception. Antimalarial agents, sulfasalazine, azathioprine and ciclosporin are compatible with pregnancy, and so can be administered until birth. Corticosteroids and analgesics such as paracetamol (acetaminophen) can also be used throughout pregnancy. NSAIDs can be safely administered until gestational week 32. The most important consideration when managing rheumatoid arthritis medications during pregnancy is that therapy must be tailored for the individual patient according to disease activity.
20309696 [The role of TNF-alpha as pain mediator]. 2010 May Tumor necrosis factor (TNF)-alpha is not only a proinflammatory mediator but also a pain mediator. Numerous nociceptors express the TNF receptors 1 and 2. By a direct action at the nociceptor TNF-alpha is involved in the generation and maintenance of inflammation-related pain.
19922330 Differential affinity of serum amyloid A1 isotypes for high-density lipoprotein. 2009 Dec Serum amyloid A (SAA), a precursor of reactive amyloid deposits, is a multigene product. SAA1, predominant both as an amyloid precursor and in plasma, consists of three allelic variants (SAA1.1, SAA1.3, and SAA1.5). Several investigations have shown that the SAA1.3 allele is associated with susceptibility to AA-amyloidosis in Japanese, and the SAA1.5 allele is related with higher serum concentrations of SAA. However, these results have not been interpreted functionally. This study assessed the affinity of SAA isotypes for high-density lipoprotein (HDL), to which SAA binds in plasma. Using a surface plasmon resonance-based apparatus (BIAcore), the affinity between immobilized recombinant human SAAs and HDL was determined. The SAA concentration was measured in fractions after ultracentrifugation (d = 1.23) of sera from patients with rheumatoid arthritis, whose SAA1 genotypes were determined. In the BIAcore analysis, as the dissociation reaction under the conditions used was too rapid to fit the typical kinetic model, the steady-state affinity model was used. The affinity (kd) of SAA1.1, SAA1.3, and SAA1.5 for HDL was 1.4 x 10(-5), 1.8 x 10(-5), and 3.7 x 10(-6), respectively. rSAA1.5 showed significantly (p < 0.05) stronger affinity than the other two. The fraction of lipid-free SAA in serum was significantly (p < 0.001) lower in the patients with larger numbers of the 1.5 allele at the SAA1 locus. These results suggest that the relatively high affinity of SAA1.5 may cause the high serum concentration and may be related to the low susceptibility to amyloidosis.
19796586 Ankle function and sports activity after total ankle arthroplasty. 2009 Oct BACKGROUND: The return to sporting activities after ankle arthroplasty has rarely been evaluated. The purpose of the present study was to evaluate function and return to sports after total ankle arthroplasty. MATERIALS AND METHODS: One hundred seventy-nine Salto Total Ankle Arthroplasties (TAA) were implanted between 1997 and 2005. A self-administered questionnaire including the Foot Function Index (FFI) and Foot and Ankle Ability Measurement (FAAM) was sent to all patients. At last followup, six were deceased, 22 were not available for evaluation, and six questionnaires were incomplete. One hundred forty-five questionnaires were available. The mean age was 60.9 years and the mean followup was 53.8 months. The main indications for TAA were osteoarthritis (OA) in 100 cases and Rheumatoid arthritis (RA) in 40 cases. RESULTS: 15.2% of the patients said that their operated ankle was "normal'' 60.7%" nearly normal''; 20% "abnormal'' and 4.1% "highly abnormal.'' The FFI scores were 13.7 +/- 17 for "activity limitations'', 31.7 +/- 23 for "disability'' and 16.9 +/- 19 for "pain''. The FAAM scores were 74.9 +/- 18 for activities of daily living and 48.9 +/- 28 for sports activities. On a Visual Analog Scales (0 to 100 were 100 is the "pre-pathology level'') the mean rating was 70.2 +/- 19.6 for Activities of Daily Living and 53.7 +/- 28 for sport activities. In the OA patients, 38 regularly road bicycle, 21 perform recreational gymnastics, 58 swimming, 50 home gardening, 27 dancing, and 43 hiking. Seven patients regularly practice tennis, nine cross-country skiing, 17 downhill skiing, and six regularly run more than 500 m. CONCLUSION: This study showed that TAA improved the quality of life and that return to recreational activities was generally possible but the return to impact sport was rarely possible.
21115463 Self-reported flaring varies during the menstrual cycle in systemic lupus erythematosus co 2011 Apr OBJECTIVE: We studied self-reported flares before menses in SLE, RA and FM, and determined whether there were differences. METHODS: Part 1: women blinded to study hypothesis having menses with SLE and RA completed a 100-day diary logging their pain, fatigue and disease activity on a 100-mm visual analogue scale (VAS) and menses. Part 2: SLE, RA and FM patients were mailed a questionnaire about menstrual cycle and disease changes. RESULTS: Part 1: 28 patients with SLE and 21 with RA were included; 84% of SLE and 71% of RA patients had regular menses. Patients with SLE had higher pain, fatigue and disease activity during menses than in the hormonal surge phase. Patients with RA had increased pain, fatigue and disease activity during decreasing progesterone. Part 2: 498 patients were surveyed, of whom 56% responded (81 SLE, 136 RA and 61 FM). Those taking the oral contraceptive pill (OCP) ever since diagnosis were 52% with SLE, 41% with RA and 33% with FM (P = 0.1). Those who flared before menses when not on OCP were 36% with SLE, 28% with RA and 54% with FM (P = 0.08). In SLE patients, the mean VAS scores were worse during menses with average scores of 21.0 for pain, 26.7 for fatigue and 18.2 for disease activity vs 16.0 (P = 0.04), 18.6 (P = 0.004) and 11.4 (P = 0.01) during the surge. In RA, the decreasing progesterone phase was different from the increasing oestrogen phase for pain (P = 0.06). CONCLUSION: There could have been recall bias and participants may have confused pre-menstrual syndrome with flares. However, there seem to be menstrual cycle flares in SLE, RA and FM.
20975634 NEAR study: Needs and Expectations in Rheumatoid ARthritis - do we know our patients needs 2010 Jul INTRODUCTION: Rheumatoid arthritis is a chronic systemic inflammatory rheumatic disease whose characteristics have a clear impact on the life of the patient and his/ her family. Doctor-patient relationship is increasingly based on communication and information transfer. In the case of chronic diseases and especially in RA, that information is fundamental for a better compliance, but also for the prevention of problems and the patient's better management of the disease on a daily basis. OBJECTIVES: To determine in a population of RA patients which are the principal sources of information about the disease, what unmet needs exist and the level of patient involvement in therapeutic decision. METHODS: We applied a questionnaire in person and by telephone to a population of patients with rheumatoid arthritis fulfilling the criteria of the ACR, which were followed at several departments of rheumatology in mainland Portugal, about their expectations, the degree and type of information they expected, and their unmet needs. RESULTS: A total of 223 RA patients filled in the questionnaire, 82.5% of which were female, mean age 55.13 +/- 14.49 years and whose mean duration of disease was above 5 years in 69.5% of the individuals. Of these, 17.5% found that RA had an impact on quality of life, 15.7% felt that RA affected their ability to enjoy life and 14.3% had difficulties in performing activities of daily living. Some activities were found to be more difficult for a patient with RA (on a scale of 0 to 10), such as gardening (6.36) and practicing sports (5.79). Other basic tasks were also considered difficult, as are the case of household chores (5.76) sleeping (5.08) walking (4.99) and working (4.86). Regarding the clinical impact of RA, as expected pain is almost a universal factor (87.9%), although the majority of patients also refer arthritis (78%), pain when moving (65.5%), fatigue (60.1%) and joint deformities (58.3%) as very common symptoms. Diminishing pain (81.2%), a general improvement of symptoms (73.1%) in a lasting way (57.4%) and reducing arthritis (59.2%) appeared as the main concerns of patients with RA. Regarding quality of information, 68.2% of patients consider they are well informed about the disease, but these numbers decrease if we consider information about treatment options (46.2%), the concept of remission (20.6%) or the recognition of the DAS 28 scale (17%). As preferred sources of information about the disease, 67.7% of individuals indicate their rheumatologist, 31.4% their general practitioner, 17% the Internet and 9% the attending nurse. The same order is obtained when asked about treatment information. As to the need for additional information, the patients refer «more information about therapies/treatments» (26.9%), «new scientific developments and social support» (17.5% each), «how to improve symptoms and live better in everyday life» (16.6%). «What is the disease» (6.7%) is referred last, being that only 8.1% of patients consider they are well informed. In what concerns discussion and participation in the process of clinical decision about medication, 56.1% of patients say that they share it with their doctors during their consultation. CONCLUSION: These results, which somewhat differ from the existing literature, demonstrate that there are important issues that should be considered in clinical practice, both relating to clinical issues and the unmet needs of our patients. We are unaware of the results coming from a treatment strategy designed to increase the RA patient's perception of their general state of health or of their perception of function. We should, however, keep in mind that pain, wellbeing and disease activity (as well as remission) should be important goals in therapeutic strategies that are to be increasingly shared with our patients.
20175883 Discrepancy between the in vitro and in vivo effects of murine mesenchymal stem cells on T 2010 INTRODUCTION: The goal of this study is to analyze the potential immunosuppressive properties of mesenchymal stem cells (MSC) on T cell proliferation and in collagen-induced arthritis (CIA). An additional aim is to investigate the role of interferon-gamma (IFN-gamma) in these processes. METHODS: MSC were isolated from bone marrow of DBA/1 wild type and IFN-gamma receptor knock-out (IFN-gammaR KO) mice and expanded in vitro. Proliferation of anti-CD3-stimulated CD4+ T cells in the presence or absence of MSC was evaluated by thymidine incorporation. CIA was induced in DBA/1 mice and animals were treated with MSC by intravenous or intraperitoneal injections of wild type or IFN-gammaR KO MSC. RESULTS: Purity of enriched MSC cultures was evaluated by flow cytometry and their ability to differentiate into osteoblasts and adipocytes. In vitro, wild type MSC dose-dependently suppressed anti-CD3-induced T cell proliferation whereas IFN-gammaR KO MSC had a significantly lower inhibitory potential. A role for inducible nitric oxide (iNOS), programmed death ligand-1 (PD-L1) and prostaglandin E2 (PGE2), but not indoleamine 2,3-dioxigenase (IDO), in the T cell inhibition was demonstrated. In vivo, neither wild type nor IFN-gammaR KO MSC were able to reduce the severity of CIA or the humoral or cellular immune response toward collagen type II. CONCLUSIONS: Whereas MSC inhibit anti-CD3-induced proliferation of T cells in vitro, an effect partially mediated by IFN-gamma, MSC do not influence in vivo T cell proliferation nor the disease course of CIA. Thus there is a clear discrepancy between the in vitro and in vivo effects of MSC on T cell proliferation and CIA.
19856711 Adrenal plasma steroid relations in glucocorticoid-naïve premenopausal rheumatoid arthrit 2009 Apr OBJECTIVE: Clinical and experimental data indicate the involvement of adrenal steroids in the complex of rheumatoid arthritis (RA) pathogenesis. A subtle adrenocortical hypocompetence has been suggested in a subset of glucocorticoid-naïve premenopausal females with RA. METHODS: The interrelations among adrenal steroids: cortisol (CORT), 17alpha-hydroxyprogesterone (17-OHP), androstenedione (ASD), dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS) were evaluated in 15 glucocorticoid-naïve premenopausal females with RA and in 14 age- and body mass index- matched healthy females at basal and during insulin-induced hypoglycemia states. Spearman's correlations were used to analyze baseline plasma concentrations as well as areas under response curves of these steroids levels as assayed during the basal and/or insulin-induced hypoglycemia status. RESULTS: Six among 15 RA patients, but none of 14 controls had combined "lower" quartile range of basal cortisol (< 431 nmol/l) and lower DHEAS (< 2.79 micromol/l) levels, i.e., concentrations within the lowest quartiles of the control group (p = 0.017). In all subjects combined, basal correlations were significantly positive between ASD and other steroids (CORT, 17OHP, DHEA, DHEAS). When patient and control groups were analyzed separately, the positive basal correlation between ASD and CORT was significant only in RA patients (p = 0.030). In contrast, a positive basal correlation between ASD and DHEA was significant only in controls (p = 0.004). When comparing the areas under response curves (AUCs), the correlation of ASD and CORT was significantly negative in RA (p = 0.009), but positive in controls (RA vs control difference in Spearman's correlations, p = 0.002). The correlation between AUCs of ASD and DHEA was strongly positive in controls (p = 0.006), but not in RA (RA vs. control difference p = 0.044). CONCLUSIONS: The results suggest relative hypocompetence of adrenocortical function in premenopausal RA females. Different patterns of correlations of the adrenal steroids during basal vs. stimulatory testing suggested certain alterations in adrenal synthetic pathways or deficiencies in the dynamics of steroidogenesis in RA.
20374384 The effects of an orally administered probiotic on sulfasalazine metabolism in individuals 2010 Feb 1 AIM: To carry out a pilot study to investigate the effect of short-term oral probiotic administration on the metabolism of sulfasalazine (SSZ) in patients with rheumatoid arthritis (RA) stabilized on SSZ. METHODS: Twelve subjects with RA taking stable doses of SSZ for a minimum of 3 months prior to the study, received a probiotic preparation contained three strains of bacteria (1.8 x 10(9) CFU/day) twice daily for 1 week. Single point blood and 12-h urine samples were taken before and after probiotic treatment and 3 weeks following discontinuation of probiotics, for determination of SSZ and its metabolites. The presence of the probiotic bacteria in the feces of patients was investigated by denaturing gradient gel electrophoresis (DGGE). RESULTS: Adverse events recorded were three instances of gastrointestinal disturbance and one flare of RA. Plasma and urinary levels of SSZ and its metabolites showed no statistically significant changes after probiotic administration and the incidence of gastrointestinal disturbance did not appear to be ascribed to higher sulfapyridine plasma levels. Probiotic-specific DGGE bands were detected in the feces of some patients after the treatment period. CONCLUSIONS: Short-term treatment of RA patients with a multi-strain probiotic did not significantly influence SSZ metabolism as has been demonstrated in animal models.
20847326 A dual-monoclonal sandwich ELISA specific for hepcidin-25. 2010 Nov BACKGROUND: Hepcidin, a key regulator of iron metabolism, binds to the iron transporter ferroportin to cause its degradation. In humans, hepcidin deficiency has been linked to hemochromatosis and iron overload, whereas increased concentrations have been reported in anemia of cancer and chronic disease. There is currently an unmet clinical need for a specific immunoassay with a low limit of quantification to measure serum concentrations of hepcidin-25, the active form of the protein. METHODS: We generated 2 antihepcidin-25 monoclonal antibodies and used them to build a sandwich ELISA. We correlated ELISA results to hepcidin-25 measurements by LC-MS and used ELISA to measure serum hepcidin-25 concentrations in normal individuals, cancer patients, and patients with rheumatoid arthritis. RESULTS: The sandwich ELISA was highly specific for hepcidin-25, having a limit of quantification of 0.01 μg/L (10 pg/mL). Serum concentrations of hepcidin-25 measured by ELISA correlated with hepcidin-25 concentrations measured by using an independent LC-MS assay (r = 0.98, P < 0.001). Hepcidin-25 concentrations were increased in patients with cancer (median 54.8 μg/L, 25%-75% range 23.2-93.5 μg/L, n = 34) and rheumatoid arthritis (median 10.6 μg/L, 25%-75% range 5.9-18.4 μg/L, n = 76) compared with healthy individuals (median 1.20 μg/L, 25%-75% range 0.42-3.07 μg/L, n = 100). CONCLUSIONS: The use of 2 monoclonal antibodies in a sandwich ELISA format provides a robust and convenient method for measuring concentrations of the active form of hepcidin. This ELISA should help to improve our understanding of the role of hepcidin in regulating iron metabolism.
20487651 [The expression of TWEAKR/Fn14 in Rheumatoid arthritis fibroblast-like synoviocytes]. 2010 Jun AIM: To investigate the mechanism of TWEAK on Rheumatoid arthritis fibroblast-like synoviocytes (RA FLS) activation and articular destruction by analyzing expression of TWEAKR/Fn14 on RA FLS. METHODS: FLS was co-cultured with rhTWEAK, with TNF-alpha or IL-1beta as a synergistic stimulator. Expression of TWEAKR/Fn14 protein on RA FLS was detected by Immunocytochemistry and Western blotting. The fn14 mRNA was measured by RT-PCR. RESULTS: TWEAKR/Fn14 was expressed on the cell membrane and in the cytoplasm of RA FLS. TWEAKR/Fn14 mRNA and protein induced by 100 microg/L TWEAK were higher than the control group. TNF-alpha and IL-1beta had synergistic effect on expression of TWEAKR/Fn14 in RA FLS. CONCLUSION: TWEAKR/Fn14 was expressed on the cell membrane and in the cytoplasm of RA FLS, and recombinant TWEAK further enhanced the TWEAKR/Fn14 expression. TNF-alpha and IL-1beta had synergistic effect on the biological activity of TWEAK by increasing the expression of TWEAKR/Fn14 on RA FLS.
20108015 Inclusion body myositis in a patient with long standing rheumatoid arthritis treated with 2010 May Adult inflammatory myopathies are rare conditions. Amongst them, inclusion body myositis (IBM) is considered to be the most common acquired myopathy in adults above 50 years of age, follows a slowly progressive course, and ultimately leads to severe disability. The case of a 57-year-old patient with long standing rheumatoid arthritis (RA) who developed muscle wasting and weakness of the quadriceps femoris after initiation of anti-TNFalpha treatment is presented. Further workup including muscle biopsy revealed IBM. Initiation of rituximab for continuing synovial inflammation led to remission of RA, but no amelioration of muscle weakness was noted. Although cases of IBM in patients with autoimmune disorders have occasionally been reported and are believed to more favourably respond to immunosuppressive treatment, our patient was unresponsive to glucocorticoids. Furthermore, deterioration of muscle strength was noted with both adalimumab and etanercept treatment. Rituximab, not previously used in IBM, successfully controlled RA, but showed no effect on muscle strength. The present case underlines the therapeutic difficulties in IBM and suggests that anti-TNFalpha therapy might even be deleterious. While an early trial of the lymphocyte-depleting antibody alemtuzumab in IBM showed promising results, selective anti-B-cell-therapy remained without effect in our patient.
19370307 Toxic hepatitis induced by infliximab in a patient with rheumatoid arthritis with no relap 2009 Aug We present a case of toxic hepatitis related to infliximab treatment in a 38-year-old woman with rheumatoid arthritis (RA). The patient had previously been treated with different disease-modifying drugs (DMARDs) alone or in combination but had never revealed signs of liver dysfunction. Due to high disease activity, treatment with infliximab (3 mg/kg i.v.) was initiated in combination with methotrexate (MTX) (25 mg/week) and folic acid (5 mg/week). The patient stopped MTX and folic acid on her own initiative after 3 weeks due to improvement of joint symptoms. After seven infusions, progressive elevations of the transaminases up to five times the upper normal limit were noted and treatment with infliximab was terminated. Serological tests for viral and autoimmune hepatitis and for ANA and anti-dsDNA were all negative. Specific infliximab antibodies could not be detected. Ultrasound of the liver was normal. Liver biopsy showed late signs of acute toxic hepatitis without MTX-related fibrosis. This is one the first cases that convincingly demonstrates that infliximab treatment may cause toxic hepatitis. Moreover, the case suggests a lack of hepatic cross-toxicity between infliximab and etanercept as the patient continued with etanercept without new episodes of liver dysfunction.
20801615 Five cases of failure of the tibial polyethylene insert locking mechanism in one design of 2011 Sep We describe 5 cases of failure of the locking mechanism of the polyethylene insert and tibial base-plate in one design of constrained condylar knee prosthesis due to disengagement of the locking screw. Loosening of the screw is believed to occur because of a counterclockwise torque created by the axial rotation of the femur on the tibia that occurs as the knee extends during gait. This torque is transmitted via the highly rotationally constrained femoral housing and tibial post to the locking screw. These failures suggest that an alternative locking mechanism should be considered for this prosthesis.
19924542 Biodistribution mechanisms of therapeutic monoclonal antibodies in health and disease. 2010 Mar The monoclonal antibody market continues to witness an impressive rate of growth and has become the leading source of expansion in the biologic segment within the pharmaceutical industry. Currently marketed monoclonal antibodies target a diverse array of antigens. These antigens are distributed in a variety of tissues such as tumors, lungs, synovial fluid, psoriatic plaques, and lymph nodes. As the concentration of drug at the proximity of the biological receptor determines the magnitude of the observed pharmacological responses, a significant consideration in effective therapeutic application of monoclonal antibodies is a thorough understanding of the processes that regulate antibody biodistribution. Monoclonal antibody distribution is affected by factors such as molecular weight, blood flow, tissue and tumor heterogeneity, structure and porosity, target antigen density, turnover rate, and the target antigen expression profile.
20722022 CD248 and its cytoplasmic domain: a therapeutic target for arthritis. 2010 Dec OBJECTIVE: CD248 is a transmembrane glycoprotein expressed on the surface of activated perivascular and fibroblast-like cells. This study was undertaken to explore the function of CD248 and its cytoplasmic domain in arthritis. METHODS: Synovial tissue biopsy samples from healthy controls, from patients with psoriatic arthritis (PsA), and from patients with rheumatoid arthritis (RA) were stained for CD248. Transgenic mice that were CD248-deficient (CD248-knockout [CD248(KO/KO) ]) or mice with CD248 lacking the cytoplasmic domain (CD248(CyD/CyD) ) were generated. Collagen antibody-induced arthritis (CAIA) was induced in these mice and in corresponding wild-type (WT) mice as controls. Clinical signs and histologic features of arthritis were evaluated. Cytokine levels were determined by enzyme-linked immunosorbent assay, and the number of infiltrating inflammatory cells was quantified by immunohistochemistry. In vitro studies were performed with fibroblasts from CD248-transgenic mouse embryos to explain the observed effects on inflammation. RESULTS: Immunostaining of synovium from patients with PsA and patients with RA and that from mice after the induction of CAIA revealed strong CD248 expression in perivascular and fibroblast-like stromal cells. CD248(KO/KO) and CD248(CyD/CyD) mice had less severe arthritis, with lower plasma levels of proinflammatory cytokines, as compared with WT controls. Moreover, the joints of these mice had less synovial hyperplasia, reduced accumulation of inflammatory cells, and less articular cartilage and bone damage. Tumor necrosis factor α-induced monocyte adhesion to CD248(CyD/CyD) fibroblasts was impaired. CD248(CyD/CyD) fibroblasts exhibited reduced expression of hypoxia-inducible factor 1α, placental growth factor, vascular endothelial growth factor, and matrix metalloproteinase 9 activity in response to transforming growth factor β. CONCLUSION: CD248 contributes to synovial hyperplasia and leukocyte accumulation in inflammatory arthritis, the effects of which are mediated partly via its cytoplasmic domain. CD248 is therefore a potential new target in the treatment of arthritis.