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

ID PMID Title PublicationDate abstract
20864805 Therapeutic antibodies directed at G protein-coupled receptors. 2010 Nov G protein-coupled receptors (GPCRs) are one of the most important classes of targets for small molecule drug discovery, but many current GPCRs of interest are proving intractable to small molecule discovery and may be better approached with bio-therapeutics. GPCRs are implicated in a wide variety of diseases where antibody therapeutics are currently used. These include inflammatory diseases such as rheumatoid arthritis and Crohn disease, as well as metabolic disease and cancer. Raising antibodies to GPCRs has been difficult due to problems in obtaining suitable antigen because GPCRs are often expressed at low levels in cells and are very unstable when purified. A number of new developments in over-expressing receptors, as well as formulating stable pure protein, are contributing to the growing interest in targeting GPCRs with antibodies. This review discusses the opportunities for targeting GPCRs with antibodies using these approaches and describes the therapeutic antibodies that are currently in clinical development.
20360185 More night than day--circadian rhythms in polymyalgia rheumatica and ankylosing spondyliti 2010 May The circadian rhythm of symptoms in patients with chronic inflammatory diseases is well known. Circadian rhythms could be used to identify targets for time-adapted antiinflammatory therapies, which are administered prior to the flare of cytokine synthesis and inflammatory activity. In recent years, the diurnal variations in rheumatoid arthritis have been described precisely for pain, stiffness, and functional disability, as well as the underlying cyclic variations in hormone levels and cytokine concentrations. This review summarizes the current knowledge on circadian rhythms in other rheumatic diseases, focusing on polymyalgia rheumatica and ankylosing spondylitis.
20306959 Treatment of chronic wounds at the olecranon. 2010 Feb Surgical resection of the olecranon bursa may be complicated by wound healing problems. Treatment with debridement and primary skin closure can be attempted. We reviewed eight patients in whom this approach had failed. In four patients we achieved wound healing with a pedicled flap (three antecubital fasciocutaneous island flaps and one radial forearm flap). In three patients the wound healed after closure of the skin and immobilization of the elbow in extension. In one elderly patient with diabetes and rheumatoid arthritis an antecubital fasciocutaneous island flap failed. It can be concluded that the antecubital fasciocutaneous island flap and primary closure of the skin followed by immobilization of the elbow in extension can be used to treat chronic wounds at the olecranon.
20018092 Integration of a priori gene set information into genome-wide association studies. 2009 Dec 15 In genome-wide association studies (GWAS) genetic markers are often ranked to select genes for further pursuit. Especially for moderately associated and interrelated genes, information on genes and pathways may improve the selection. We applied and combined two main approaches for data integration to a GWAS for rheumatoid arthritis, gene set enrichment analysis (GSEA) and hierarchical Bayes prioritization (HBP). Many associated genes are located in the HLA region on 6p21. However, the ranking lists of genes and gene sets differ considerably depending on the chosen approach: HBP changes the ranking only slightly and primarily contains HLA genes in the top 100 gene lists. GSEA includes also many non-HLA genes.
19838376 Acetabular revision using a total acetabular allograft. 2009 Apr The most challenging aspect of an acetabular revision is the management of severe bone loss, which compromises implant fixation and stability. We present a case of failed acetabular revision with extensive bone loss (Paprosky Type 3b) in a 50-year-old woman with rheumatoid arthritis, which was treated using total acetabular allograft. At a follow-up of 1 year and 3 months, the allograft had united with the host bone. This is the first report of the use of a total acetabular allograft for revision total hip arthroplasty in India. The total acetabular allograft allows the placement of the component closer to the normal hip center, provides initial stability for the acetabular component, and restores bone stock to the host pelvis.
19747396 Therapeutic implications of osteoprotegerin. 2009 Sep 12 Osteoprotegerin (OPG), a member of the tumor necrosis factor (TNF) receptor superfamily, contributes determinatively to the bone remodeling as well as to the pathogenetic mechanism of bone malignancies and disorders of mineral metabolism. There is additional evidence that OPG can promote cell survival by inhibiting TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. A number of recent in vitro, in vivo and clinical studies have defined the role of the RANK/RANKL/OPG pathway in skeletal and vascular diseases. These works were the milestone of the deep understanding of the mechanism of OPG. This review provides an overview of the potential innovative therapeutic strategies of OPG in metastatic breast and prostate carcinoma, multiple myeloma, postmenopausal osteoporosis, glucocorticoid-induced osteoporosis and rheumatoid arthritis. Special reference is given to the increasing evidence that RANKL and OPG may link the skeletal with the vascular system.
19235157 Chemical and pharmacological studies of the plants from genus Celastrus. 2009 Feb The plants of genus Celastrus, distributed in Asia, have been used as natural insecticides and folk medicines to treat fever, chill, joint pain, edema, rheumatoid arthritis, and bacterial infection in China for a long time. This contribution reviews the chemical constituents, isolated from the plants in genus Celastrus in the past few decades, and their biological activities. The compounds listed are sesquiterpenes (beta-agarofurans), diterpenes, triterpenes, alkaloids, and flavonoids.
20143007 Unexpected and persistent depletion of B lymphocytes CD20 following a minimum dose of anti 2009 Oct This study describes a woman patient suffering from rheumatoid arthritis which was resistant to treatment with the most commonly used DMARDs and anti-TNF alfa drugs, however following the administration of a minimum dose of Rituximab the patient showed a persistent and complete depletion of CD 20 lymphocytes. The dose of Rituximab administered to the patient was halted at 50 mg due to the onset of an allergic reaction. Based on these observations, a number of important speculations are possible, which however would require a larger number of case histories for their confirmation.
20080911 Vitamin D and the immune system. 2010 Mar Evidence of the role of vitamin D in the regulation of T and B cells, macrophages, dendritic cells, and keratinocytes continues to accumulate and provides a link between vitamin D and many autoimmune diseases, including Crohn's disease, juvenile diabetes mellitus, multiple sclerosis, asthma, and rheumatoid arthritis. Considering the influence of vitamin D on the immune system, it may have potential as a treatment for immune-mediated diseases, even if additional research is required to better quantify dosage. But the biggest obstacle to its clinical use is its potent hypercalcemic effect. The calcium status of the host may influence the effect of vitamin D on immunity.
19363638 Tacrolimus (FK506): Safety and Applications in Reconstructive Surgery. 2010 Mar Tacrolimus (FK506) is a macrolide immunosuppressive drug that is approved for the prevention of allograft rejection. It is a standard component of immunosuppressive regimens currently in use for organ and reconstructive tissue transplants. The experimental literature has demonstrated potential efficacy in the management of other diseases for which transplantation does not play a role. The ability of tacrolimus to modulate the immune system and inhibit T cell activation provides a potential benefit for the treatment of disorders in which autoimmune phenomena are central to their pathogenesis such as rheumatoid arthritis and inflammatory bowel disease. Tacrolimus also has well-established neuroprotective and neuroregenerative properties through both similar and different mechanisms that have been extensively demonstrated in both small and large animal models. However, as a potent immunosuppressive agent, it can cause serious adverse effects, some of which are irreversible and potentially life threatening. This article reviews its safety under different therapeutic requirements and applications in both allogeneic and autogenous tissue reconstruction.
19252517 Is spleen tyrosine kinase inhibition an effective therapy for patients with RA? 2009 Mar Despite the success of biologic therapeutic agents that target cytokines and lymphocytes, clinical needs remain unmet in the treatment of rheumatoid arthritis (RA). The development of small-molecule inhibitors that can block critical immune signal-transduction pathways are of particular interest as novel therapies for RA. Spleen tyrosine kinase (SYK) subserves the function of Fc receptors and the B-cell receptor; as such, it is attractive as a potential therapeutic target. Weinblatt and colleagues recently performed a proof-of-concept study, which demonstrated that inhibition of SYK reduced RA disease activity and levels of disease-relevant biomarkers. Dose-limiting adverse effects include diarrhea, neutropenia and hypertension, which result from both target-dependent and off-target effects. This novel study provides the first evidence that SYK could be a useful therapeutic target in RA.
19187992 Tipping the balance: modulating the Wnt pathway for tissue repair. 2009 Mar The Wnt signaling pathway has a crucial role in regulating cell growth and differentiation and is required for tissue homeostasis and repair. Although constitutive activation of the Wnt pathway can lead to abnormal cell growth and cancer, modulation of Wnt signaling might have a therapeutic benefit for tissue regeneration in numerous diseases. Recently, preclinical studies have demonstrated that treatments with antibodies against the Wnt inhibitor Dickkopf1 (DKK1) and with the positive Wnt modulator R-Spondin1 (RSpo1) were sufficient to repair the bone lesions in multiple myeloma and rheumatoid arthritis and to restore the damaged mucosa in experimental colitis, respectively. A remarkable balance is set for Wnt signaling by secreted proteins such as RSpo1 and DKK1, which help to regulate tissue homeostasis. As physiological Wnt response is essential for the regeneration of damaged tissues, modulation of the Wnt pathway might be beneficial for the treatment of multiple human diseases.
19151961 [Successful treatment of pemphigus foliaceus with rituximab. Report of 3 cases]. 2009 Sep Treatment of autoimmune bullous diseases, especially of the pemphigus diseases, regularly requires the use of immunosuppressive drugs, often with insufficient clinical benefit but considerable side effects. A variety of autoimmune diseases (such as rheumatoid arthritis, lupus erythematosus, pemphigus vulgaris) have been successfully treated with rituximab, a chimeric monoclonal antibody against CD20, leading to a transient depletion of B cells. We report on three patients with pemphigus foliaceus who responded to rituximab after failing multiple other immunosuppressive therapies. We also examine the controversial issue of continuation therapy with rituximab in detail.
22247882 Analgesic and antipyretic activities of Momordica charantia Linn. fruits. 2010 Oct Plant Momordica charantia Linn. belongs to family Cucurbitaceae. It is known as bitter gourd in English and karela in Hindi. Earlier claims show that the plant is used in stomachic ailments as a carminative tonic; as an antipyretic and antidiabetic agent; and in rheumatoid arthritis and gout. The fruit has been claimed to contain charantin, steroidal saponin, momordium, carbohydrates, mineral matters, ascorbic acid, alkaloids, glucosides, etc. The ethanolic extract of the fruit showed the presence of alkaloids, tannins, glycosides, steroids, proteins, and carbohydrates. The present study was carried out using acetic acid-induced writhing and tail-immersion tests in mice, while yeast-induced pyrexia in rats. The ethanolic extracts (250 and 500 mg/kg, po.) showed an analgesic and antipyretic effect, which was significantly higher than that in the control rats. The observed pharmacological activities provide the scientific basis to support traditional claims as well as explore some new and promising leads.
20622285 Pyoderma gangrenosum with pure red cell aplasia. 2010 Jun Pyoderma gangrenosum is an inflammatory condition of the skin commonly associated with inflammatory bowel disease and rheumatoid arthritis, but also associated with various hematological malignancies. We describe its association with pure red cell aplasia in a four year old boy who presented with progressive skin lesions, fever and pallor, and improved with corticosteroid therapy.
18373713 A semi-parametric shared parameter model to handle nonmonotone nonignorable missingness. 2009 Mar Longitudinal studies often generate incomplete response patterns according to a missing not at random mechanism. Shared parameter models provide an appealing framework for the joint modelling of the measurement and missingness processes, especially in the nonmonotone missingness case, and assume a set of random effects to induce the interdependence. Parametric assumptions are typically made for the random effects distribution, violation of which leads to model misspecification with a potential effect on the parameter estimates and standard errors. In this article we avoid any parametric assumption for the random effects distribution and leave it completely unspecified. The estimation of the model is then made using a semi-parametric maximum likelihood method. Our proposal is illustrated on a randomized longitudinal study on patients with rheumatoid arthritis exhibiting nonmonotone missingness.
20516021 Profile of Indian patients with juvenile onset chronic inflammatory joint disease using th 2010 Aug 1 OBJECTIVE: To assess the current International League of Associations for Rheumatology (ILAR) classification criteria (Edmonton, 2001) for juvenile idiopathic arthritis (JIA) in Indian patients. METHODS: Out of 441 children, 330 with chronic joint pains were diagnosed with juvenile onset chronic inflammatory arthritis and followed in an observational cohort. Our study was carried out from 1994 to 2006 in a community rheumatology clinic. Emphasis was placed on obtaining data required by the ILAR system. Of the original group, 235 children were eventually classified as having JIA; 108 were examined during the first year of illness. RESULTS: We assigned 224 children (95%) to discrete JIA categories: enthesitis-related arthritis (ERA; 36%), oligoarthritis (OLA-persistent; 17%), polyarthritis rheumatoid factor (RF)-negative (17%), polyarthritis RF-positive (12%), systemic arthritis (8%), OLA-extended (4%), and psoriatic arthritis (1%). The remaining 11 children (5%) were classified with undifferentiated arthritis (mostly an overlap due to seropositive RF and/or HLA-B27). The prevalence of ERA (89% HLA-B27-positive) and seropositive RF was unexpectedly high. Although agreement (kappa > 0.79) with the American College of Rheumatology criteria and the European Spondylarthropathy Study Group criteria was good to excellent, the ILAR system was found to be more comprehensive and clinically homogeneous. However, some problems appear unique in our scenario. CONCLUSION: A wide-spectrum phenotype of JIA is demonstrated by an Indian cohort. Although useful, RF and HLA-B27 in this population proved problematic to the ILAR classification.
20568436 [Li Wen-Rong's experience on acupuncture at painful locality taken as acupoint]. 2010 Apr Doctor Li Wen-Rong, who has been practicing acupuncture for five decades by combination of the meridian theory of TCM and related modern medical science, has still been active in acupuncture clinic, especially in acupuncture manipulation based on the method of acupuncture at painful locality taken as acupoint, Jiaji (EX-B 2) being selected as the main acupoints and Back-shu acupoints of the Bladder Meridian as adjuvant acupoints, except the acupoints on the limbs, and the selected acupoints being relatively concentrated and the needles being inserted in tender points for treatment of relevant nervous system diseases and complicated chronic cases, which has formed her own academic style. In this article, the authors introduce some of her medical records by using acupuncture manipulation based on the method of acupuncture at painful locality taken as acupoint for treatment of facial paralysis, renal colic and rheumatoid arthritis, and the main idea of this article is to summarize and analyze her academic thoughts.
20102681 Biologic therapy for systemic lupus erythematosus. 2010 Jan A new era in the treatment of systemic lupus erythematosus (SLE) may be dawning. Twelve years after the first approval of biologic therapy for patients with rheumatoid arthritis, the positive results of two large trials of a novel biologic therapy for SLE have raised hopes that a new approach to treatment may be at hand. This encouraging news follows several disappointments in trials of other biologic therapies and provides a timely moment to reflect on where we stand, what we have learned, and what may lie ahead.
19962627 Flowsheets that include MDHAQ physical function, pain, global, and RAPID3 scores, laborato 2009 Nov Electronic medical records (EMR) are used increasingly in contemporary medical care. Function, pain, global status, and RAPID3 scores remain important considerations in all rheumatic diseases. Inclusion of these scores in a flowsheet that also includes laboratory tests and medications could transform the EMR into a true medical database. Flowsheets are presented for patients with rheumatologic diagnoses other than rheumatoid arthritis to illustrate the value of the multidimensional health assessment questionnaire and RAPID3 scores in an electronic database for an EMR.