Browse

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

ID PMID Title PublicationDate abstract
19112808 Interstitial granulomatous dermatitis associated with darifenacin. 2008 Sep Interstitial granulomatous dermatitis is most commonly associated with rheumatoid arthritis (RA) but may be induced by medications as well. Darifenacin is a muscarinic antagonist which was FDA approved for the treatment of overactive bladder in December 2004. The authors describe a case of interstitial granulomatous dermatitis associated with darifenacin.
19060351 Persistent sciatic artery complicated by aneurysm formation and thrombosis. 2008 Dec A persistent sciatic artery is a rare embryological anomaly. We report a case of a persistent sciatic artery with aneurysm formation and thrombosis in a patient with rheumatoid arthritis/systemic lupus erythematosus overlap syndrome and Raynaud's phenomenon. The diagnosis and complete, accurate evaluation of the arterial anatomy of the lower limb were achieved using computed tomographic angiography.
18488052 Effects of inflammation on pharmacokinetics/pharmacodynamics: increasing recognition of it 2008 Jun Inflammation is an interesting phenomenon that crosses many disciplines as part of the host response to disease, whether it is the acute response to an infectious, traumatic, or surgical event or the more chronic responses to systemic disease such as malignancy, rheumatoid arthritis, asthma, inflammatory bowel disease, or diabetes. The impact of inflammatory states on the variability in drug response should be an integral part of research conducted across disciplines within clinical pharmacology.
17457039 Hsp60 and Hspl0 as antitumor molecular agents. 2007 Apr The molecular chaperones Hsp60 and Hsp10 are, according to recent reports, involved in cancer development and progression. We, for instance, have found that their expression varies with distinctive patterns in different malignancies: they are overexpressed in colorectal, exocervical and prostate carcinogenesis, and colorectal cancer progression, but they are downregulated during bronchial carcinogenesis. There is also evidence showing that Hsp60 and Hsp10 can be used as therapeutic agents, for example in rheumatoid arthritis. In view of these findings we want now to call attention to the potential of Hsp60 and Hsp10 in cancer therapy.
17323251 [Retrobulbar optic neuritis associated with Infliximab]. 2007 Feb CASE REPORT: We report the case of a 76-year-old woman who attended our hospital because of a sudden loss of visual acuity in her left eye. The problem appeared to be that of retrobulbar optic neuritis. However, the age of the patient together with the simultaneous use of Infliximab to treat her rheumatoid arthritis, suggests the demyelination may have been associated with the Infliximab use. DISCUSSION: TNFa inhibitors (including Infliximab) are associated with demyelinating diseases including optic neuritis.
17396109 Primer: establishing a clinical trial unit - regulations and infrastructure. 2007 Apr The performance of clinical trials can be very rewarding for the practicing or academic clinical rheumatologist. There are at least 50 new compounds - small molecules and biologics - in development for rheumatic diseases such as rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, ankylosing spondylitis, psoriatic arthritis, scleroderma, gout and fibromyalgia. Clinical trials are important to try to determine the appropriate use of these compounds, as well as to answer questions about their safety. To carry out clinical trials effectively, the physician-investigator must be aware of, and adhere to, the regulatory requirements. The purpose of this article is to review these requirements in depth, as well as to discuss the infrastructure required to establish a successful clinical trial unit.
16652230 Matrix metalloproteinase-9 and autoimmune diseases. 2006 Jul Matrix metalloproteinases (also named matrixin or MMPs) are a major group of enzymes that regulate cell-matrix composition by using zinc for their proteolytic activities. They are essential for various normal biological processes such as embryonic development, morphogenesis, reproduction tissue resorption, and remodeling. Metalloproteinases also play a role in pathological processes including inflammation, arthritis, cardiovascular diseases, pulmonary diseases and cancer. Herein we review the involvement of MMP-9 in a variety of autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, systemic sclerosis, rheumatoid arthritis, multiple sclerosis, polymyositis and atherosclerosis. MMP-9 plays either a primary or secondary role in each one of those autoimmune diseases by its up or down-regulation. It is not expressed constantly but rather is induced or suppressed by many regulating molecules. This feature of MMP-9 along with its involvement in disease pathogenesis turns it into a target for therapy of autoimmune diseases.
18466529 Comparing strategies for evaluation of candidate genes in case-control studies using famil 2007 The goal of this analysis is to compare different test strategies for genetic association in case-control studies using related individuals. The first test is the trend test that is corrected for related individuals on the basis of identity-by-descent information. The second approach is to use generalized estimating equations to adjust for the correlation between relatives, and the third is the multiple outputation method. We compare the power of these test strategies in a simulation study, and apply these methods to a candidate gene dataset of Genetic Analysis Workshop 15 from the North American Rheumatoid Arthritis Consortium.
17121482 Rheumatology in 2006: crossroads or crisis? 2006 Rheumatology has made remarkable advances in patient treatment in the past decade related to the impressive array of new drugs that have been approved or are undergoing clinical trial. While this situation should engender optimism for the future, concerns about sustaining momentum have been raised. These concerns relate to uncertainty in the research agenda for major diseases such as osteoarthritis and fibromyalgia, lack of informatics systems to allow accurate assessment of risks and benefits of new treatments, and a paucity of clinical trials in rheumatoid arthritis aimed at sustained remission or cure. Fortunately, the opportunities for the future remain very bright because of burgeoning research in biomedicine and outcomes assessment as well as progress in developing personalized medicine to individualize treatment better.
17088744 [Osteoid osteoma of the olecranon]. 2006 Sep We report a case of osteoid osteoma of the olecranon which developed in the greater sigmoid cavity. The patient was a 22-year-old male who complained of arthritic-like symptoms limited to the elbow joint and progressing for three years. Rheumatoid arthritis then tuberculosis were entertained as possible diagnoses. The diagnosis of osteoid osteoma was not established until the disease had progressed for three years and had already become stiff due to epiphyseal remodeling. Resection of the nidus only alleviate pain and joint motion was not improved.
17729039 Protein tyrosine phosphatase PTPN22 in human autoimmunity. 2007 Sep The discovery that a single-nucleotide polymorphism (SNP) in lymphoid tyrosine phosphatase (LYP), encoded by the PTPN22 gene, is associated with type 1 diabetes (T1D) has now been verified by numerous studies and has been expanded to rheumatoid arthritis, juvenile rheumatoid arthritis (JRA), systemic lupus erythematosus, Graves' disease, generalized vitiligo and other human autoimmune diseases. In this paper, we discuss the association of PTPN22 with autoimmunity, the biochemistry of the PTPN22-encoded phosphatase, and the molecular mechanism(s) by which the disease-predisposing allele contributes to the development of human disease.
29320067 2007 Jun Background: Treatment with tumour necrosis factor alpha (TNF-α, or simply TNF) inhibitors is considered to be an alternative to the use of traditional disease-modifying anti-rheumatic drugs (DMARDs) in patients with different rheumatic diseases, i.e. rheumatoid arthritis (RA). There are three TNF-inhibitor drugs currently available on the market (brand names in brackets): adalimumab (Humira), etanercept (Enbrel) and infliximab (Remicade). The Norwegian Knowledge Centre for the Health Services has previously summarised the evidence on the drugs’ efficacy and safety (in randomised clinical trials and observational studies) while the present report considers cost-effectiveness of the drugs for rheumatoid arthritis. After considerable growth over several years, the aggregate sales of the three drugs amounted to 860 million NOK in 2006. RA is a serious disease, not least from an economic perspective. No cost-of-illness studies have been found for Norway, but studies from Sweden suggest that the costs of the disease are substantial with a large proportion related to loss of work capacity. Methods: We undertook a review of economic evaluations of TNF-inhibitors against RA, and considered an analysis of health-related quality of life data for patients on TNF-inhibitors and DMARD users from a Norwegian observational study. Results: A total of twelve studies from six countries were included in the literature review. The studies were based on health economic models, which were diverse in their characteristics, and therefore the estimates of cost-effectiveness varied significantly. Conclusions: In our review of economic evaluations of TNF-inhibitors, we found significant variation in the type and features of the models used, which led to a wide range of estimates. The potential for direct comparisons of results between the studies, and thus transferability of results into Norwegian setting, is limited. With this in mind, our main conclusions are as follows: First line therapy: TNF inhibitors seem not to be cost-effective as first line therapy, based on the one study in which this was considered. Second line therapy: We cannot draw any conclusions, since no relevant studies were found. Third line therapy: TNF-inhibitors may be cost-effective, particularly in the case of patients in early disease. The drugs are also likely to be more cost-effective for patients who experience a good rather than a moderate response. Indirect costs: Prevention of productivity loss may account for considerable savings, but has only been accounted for in a few of the economic evaluations.
19066899 Prevalence of rheumatic diseases and disability in China. 2009 Mar The objective of this study was to provide a single source for the best available estimates of the national prevalence of common rheumatic disorders and rheumatic disability by reviewing the epidemiological surveys conducted in China. Relevant publications were retrieved by search engines in both the English and the Chinese language web sites. Only community-based surveys conducted in China were included. A pooled prevalence with 95% confidence interval was calculated. Forty-one surveys met the inclusion criteria. Prevalence of rheumatic pain varied from 11.6 to 46.4%, with significantly higher rate in northern China in comparison to the southern part. Prevalence of rheumatic disability, however, did not increase with higher latitude. Limitation to daily life and work was 1-2 and 3-6%, of general population, respectively. The pooled prevalence of rheumatoid arthritis, ankylosing spondylitis, and undifferentiated spondylarthropathy is 0.37, 0.22 and 0.57%, respectively. The estimated prevalence is 37.7/100,000 for systemic lupus erythematosus, and 0.45% for primary Sjögren's syndrome. In the past decade, prevalence of gout and hyperuricemia was 0.22-0.43 and 12.1-25.2%, respectively. In elderly Chinese age >or=60, prevalence of symptomatic cervical OA, lumbar OA, knee OA and hand OA was 14.5, 24.0, 19.4, and 5.0%, respectively. Symptomatic hip OA was rare. Rheumatoid arthritis and gout are less frequent in Chinese than in Caucasians. The prevalence of ankylosing spondylitis, systemic lupus erythematosus and primary Sjögren's syndrome is comparable to that in Caucasians. In comparison to the whites, the Chinese population has a higher prevalence of knee OA, a lower prevalence of hand OA, and a much lower prevalence of hip OA.
18942334 [The influence of degenerative changes on the production of free radicals and the lipid pe 2008 Aug Since now researches claimed that rheumatoid arthritis was not characterized with an inflammatory process due to the lack of vessel in the cartilaginous tissue. Nevertheless, an inflammation of synovial membrane and a reduction of activity of articulation co-exist with rheumatoid arthritis. Recent results have proved that the above disease is connected with an oxidative stress. AIM OF THE STUDY: The aim of this investigation was to estimate changes of nitric oxide (NO) in plasma and malondialdehyd (MDA) concentration in red blood cells of patients suffering from an alloplastic of the hip joint. We also measured how physical activity in a reduced motor activity influences the NO and MDA concentration. MATERIAL AND METHODS: Malonyl dialdehyde (MDA) concentration in RBCs was assayed with Placer method, nitrogen concentration in blood plasma was determined using the Griess indirect method. Biochemical tests have been performed on a group of 36 patients with osteoarthritis hospitalised at the Traumatic-Orthopaedic Department of the Ministry of Internal Affairs and Administration Hospital in Lodz, Poland. A control group included 21 subjects with normal physical activity. RESULTS: The concentration of nitric oxide in plasma of patients that were operated was lower than in a healthy control group. Ten days after the operation it decreased, but after a month it was higher than before the operation. The concentration of MDA in red blood cells was higher before and after the alloplastic than in the healthy control group. Ten days after operation the concentration of MDA was lower about 15.8% but after 30 days it lowered up to about 26.3% in comparison to the concentration before the operation. CONCLUSIONS: Our results are not the same as those shown by other researches which suggest increased production of nitric oxide. Reduction of the motor activity due to degenerative joint disease and alloplastic causes reduction in lipid peroxidation of red blood cells.
18484698 Patient-centered rheumatoid arthritis disease activity assessment by a modified RADAI. 2008 Jul OBJECTIVE: To evaluate the psychometric properties and validity of a modified version of the Rheumatoid Arthritis Disease Activity Index (RADAI) without joint counts in order to facilitate rapid and easy RA activity assessment in daily routine. METHODS: One hundred sixty-nine outpatients with RA completed the original RADAI and the modified RADAI-5. Simultaneously, the Disease Activity Score-28-erythrocyte sedimentation rate (DAS28-ESR) and C-reactive protein (DAS28-CRP) and the Simplified Disease Activity Index (SDAI) and Clinical DAI (CDAI) were applied. Cronbach's alpha, as a measure for internal consistency, and Spearman's rho, to evaluate the linear relationship of the different disease activity scales, were calculated. Rho was determined for the RADAI-5 and the core set measures to assess convergent validity. For agreement analysis, kappa statistics were calculated. An attempt was made to estimate the modified questionnaire's sensitivity to change. RESULTS: Means for the RADAI and the RADAI-5 were 2.8 (range 0.0-9.12) and 3.07 (0-10), respectively. Other means were as follows: DAS28-ESR 3.51 (0.28-6.67), DAS28-CRP 3.19 (1.12-5.83), CDAI 11.53 (0.0-44.6), and SDAI 12.36 (0.1-44.9). Cronbach's alpha was highest for the RADAI-5 (0.917) and lowest for the DAS28-CRP (0.510). The RADAI-5 was highly significantly correlated (all p < 0.0001) to all other instruments. However, kappa was < 0.65 for the relation of the RADAI-5 and all other scores except the RADAI. Changes of the RADAI-5, DAS28-ESR, and CDAI were significantly correlated (p < 0.001). CONCLUSION: The RADAI-5, refraining from joint counts, was shown to be capable of measuring RA activity. Reliability and convergent validity could be proven.
18439312 Proinflammatory role of amphiregulin, an epidermal growth factor family member whose expre 2008 Apr 27 BACKGROUND: The epidermal growth factor (EGF) and EGF receptor (EGFR) families play important roles in the hyperplastic growth of several tissues as well as tumor growth. Since synovial hyperplasia in rheumatoid arthritis (RA) resembles a tumor, involvement of the EGF/EGFR families in RA pathology has been implied. Although several reports have suggested that ErbB2 is the most important member of the EGFR family for the synovitis in RA, it remains unclear which members of the EGF family are involved. To clarify the EGF-like growth factors involved in the pathology of RA, we investigated the expression levels of seven major EGF-like growth factors in RA patients compared with those in osteoarthritis (OA) patients and healthy control subjects. METHODS: The expression levels of seven EGF-like growth factors and four EGFR-like receptors were measured in mononuclear cells isolated from bone marrow and venous blood, as well as in synovial tissues, using quantitative RT-PCR. Further evidence of gene expression was obtained by ELISAs. The proinflammatory roles were assessed by the growth-promoting and cytokine-inducing effects of the corresponding recombinant proteins on cultured fibroblast-like synoviocytes (FLS). RESULTS: Among the seven EGF-like ligands examined, only amphiregulin (AREG) was expressed at higher levels in all three RA tissues tested compared with the levels in OA tissues. The AREG protein concentration in RA synovial fluid was also higher than that in OA synovial fluid. Furthermore, recombinant human AREG stimulated FLS to proliferate and produce several proinflammatory cytokines, including angiogenic cytokines such as interleukin-8 and vascular endothelial growth factor (VEGF), in a dose-dependent manner. The VEGF mRNA levels in RA synovia and VEGF protein concentrations in RA synovial fluid were significantly higher than those in the corresponding OA samples and highly correlated with the levels of AREG. CONCLUSION: The present findings suggest that AREG functions to stimulate synovial cells and that elevated levels of AREG may be involved in the pathogenesis of RA.
21794490 [Toward a non-empirical treatment for rheumatoid arthritis based on its molecular patholog 2008 Jan Rheumatoid arthritis (RA) is a chronic, disabbling disease that affects individuals during the productive years of their lives. Modern treatment for RA includes the so called "biologic" therapy, which is based on recombinant proteins that modify the biologic processes. These agents have potent therapeutic effects and different mechanisms of action. Nevertheless, therapeutic failure still prevails. Treatment that prevents disability in RA must be started in an early manner, before the development of complications and, ideally, with a minimum possibility of therapeutic failure. As yet, there are no clinical or laboratory criteria to identify those patients with a higher probability of responding to particular types of therapy, delaying control of RA ad affecting the prevention of incapacity. Research into gene diversity through single-nucleotide polymorphisms (SNPs) by means of microarray systems, allows the detailed analysis of gene factors associated to a given disease. SNPs have been recently applied to the study of RA, where the major polymorphisms associated to RA occur primarily in genes that code for proteins related to the initiation of an immune response and/or the control of cellular activity in the immune system, in addition to genes related to tissue repair. The specific meaning of these findings is in its initial stages of research. On the other hand, proteomics relate to the analysis of protein expression profiles at multiple levels. Both types of studies will contribute to the knowledge of patterns of gene expression in RA compared to the general population, and will allow an understanding of the pathogenesis of RA. Moreover, proteomic and genomic profiles can be employed to designs probes that identify individuals with the risk of developing RA, individually predict the response to different therapeutic modalities (pharmacogenomics) and for the follow-up of the biologic response to therapy.
18054182 Injectable actarit-loaded solid lipid nanoparticles as passive targeting therapeutic agent 2008 Mar 20 This work systematically studied the intravenous injection formulation of solid lipid nanoparticles (SLNs) loaded with actarit, a poor water soluble anti-rheumatic drug. The goal of this study was to design passive targeting nanoparticles which could improve therapeutic efficacy and reduce side-effects such as nephrotoxicity and gastrointestinal disorders commonly associated with oral formulations of actarit. Based on the optimized results of single-factor and orthogonal design, actarit-loaded SLNs were prepared by a modified solvent diffusion-evaporation method. The formulated SLNs were found to be relatively uniform in size (241+/-23 nm) with a negative zeta potential (-17.14+/-1.6 mV). The average drug entrapment efficiency and loading were (50.87+/-0.25)% and (8.48+/-0.14)%, respectively. The actarit-loaded SLNs exhibited a longer mean retention time in vivo (t(1/2(beta)), 9.373 h; MRT, 13.53 h) compared with the actarit 50% propylene glycol solution (t(1/2(ke)), 0.917 h; MRT, 1.323 h) after intravenous injection to New Zealand rabbits. The area under curve of plasma concentration-time (AUC) of actarit-loaded SLNs was 1.88 times greater than that of the actarit in 50% propylene glycol solution. The overall targeting efficiency (TE(C)) of the actarit-loaded SLNs was enhanced from 6.31% to 16.29% in spleen while the renal distribution of actarit was significantly reduced as compared to that of the actarit solution after intravenous administration to mice. These results indicated that injectable actarit-loaded solid lipid nanoparticles were promising passive targeting therapeutic agents for rheumatoid arthritis.
17001436 Reliability, validity and responsiveness of the German Short Musculoskeletal Function Asse 2006 Sep OBJECTIVE: The patient-based evaluation of outcome is gaining increased importance. The aim of the study was to demonstrate the reliability, validity and responsiveness of the German version of the Short Musculoskeletal Function Assessment Questionnaire (SMFA-D) in patients undergoing surgical or conservative treatment. METHODS: Three hundred and thirty-two patients suffering from osteoarthritis of the hip or knee, rheumatoid arthritis or rotator cuff tear undergoing surgical or medical inpatient treatment were followed up for 12 month. Patients underwent both SMFA-D and other assessments and clinical as well as radiological examinations. Reliability, validity and responsiveness of the SMFA-D were evaluated. RESULTS: Values of the SMFA-D subscales, Function index (M 22-49, SD 12-20, range 0-96) and Bother index (M 29-52, SD 15-23, range 0-100), showed a normal distribution. Internal consistency (0.88-0.97) and retest reliability (0.71-0.96) coefficients were satisfactory to excellent. In most cases, the SMFA-D correlated significantly with function tests, physicians' function ratings, patients' pain ratings and other quality-of-life questionnaires in all patient subgroups. The results support both the construct and criterion validity of the measure. Different patient groups and subgroups could be discriminated with the SMFA-D scales. The standardized response means of SMFA-D subscales were in surgical patients better than in conservatively treated patients and comparable to those of the SF-36 Physical Component Summary scale. CONCLUSIONS: The German version of SMFA is a reliable, valid and responsive questionnaire in patients with osteoarthritis of the hip or knee, rheumatoid arthritis or rotator cuff tear undergoing surgical or medical inpatient treatment. Thus, the use of the SMFA-D in these patients can be recommended.
18306005 Limits and perspectives of ultrasound in the diagnosis and management of rheumatic disease 2008 Musculoskeletal sonography (MSUS) has played a growing role in the diagnosis and management of rheumatic diseases, enabling the imaging of synovitis, bone erosion, and cartilage damage in the early phase of arthritis. "Dynamic" evaluation of tendons and help in guiding needle positioning in interventional manoeuvres are some of the other reasons for its success. MSUS, particularly when coupled with power Doppler (PD) examination, has recently been shown to be an efficient tool for monitoring disease activity and progression in rheumatoid arthritis, spondyloarthritis, crystal-related arthropathy, and osteoarthritis, with general consensus on its interesting results. More specifically, the PD signal has proved to be a simple and promising tool for short-term monitoring of synovial vascularity changes induced by steroids or biological agents in RA patients. MSUS has some limits, because of the physical properties of US and the quality of the equipment; it is, moreover, an operator-related imaging technique, with few standardized protocols. Future goals should be standardization of the examining approach in grey scale and Doppler ultrasound (US), including use of new equipment (3D US), extensive use in other fields (i.e. connective tissue diseases and vasculitis), and possible new applications (e.g. thoracic US).