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Bertolaccini M.L.,Rayne Institute
Lupus | Year: 2012

Research on antiphospholipid antibodies (aPL) and the thrombotic manifestations associated with these antibodies has grown since the description of anticardiolipin antibodies (aCL) by Harris and colleagues in the early 1980s. Antiprothrombin (aPT) antibodies are commonly detected by ELISA, using irradiated plates (aPT) or prothrombin in complex with phosphatidylserine (aPS/PT). Although aPT and/or aPS/PT are associated with antiphospholipid syndrome (APS) -related clinical features and these antibodies correlate with each other, aPT and aPS/PT belong to different populations of autoantibodies even though they can both be present in the same patient. Early studies suggested that these antibodies might be the antigenic target of lupus anticoagulant (LA) and their correlation and clinical significance is being investigated. © The Author(s), 2012. Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav. Source


Lampropoulos C.E.,General Hospital of Nafplio | Papaioannou I.,Branch of Public Hygiene | D'Cruz D.P.,Rayne Institute
Nature Reviews Rheumatology | Year: 2012

Osteoporosis is a serious health problem worldwide that is associated with an increased risk of fractures and mortality.Vascular calcification is a well-defined independent risk factor for cardiovascular disease (CVD) and mortality.Major advances in our understanding of the pathophysiology of osteoporosis and vascular calcification indicate that these two processes share common pathogenetic mechanisms.Multiple factors including proteins (such as bone morphogenetic proteins, receptor activator of nuclear factor κB ligand, osteoprotegerin, matrix Gla protein and cathepsins), parathyroid hormone, phosphate, oxidized lipids and vitamins D and K are implicated in both bone and vascular metabolism, illustrating the interaction of these two, seemingly unrelated, conditions.Many clinical studies have now confirmed the correlation between osteoporosis and vascular calcification as well as the increased risk of CVD in patients with osteoporosis.Here, we explore the proposed mechanistic similarities between osteoporosis and vascular calcification and present an overview of the clinical data that support the interaction between these conditions.© 2012 Macmillan Publishers Limited.All rights reserved . Source


Fullerton J.N.,Rayne Institute | Singer M.,University College London
Seminars in Respiratory and Critical Care Medicine | Year: 2011

The physiological and biochemical abnormalities that constitute multiple organ failure represent cellular perturbations that, importantly, need to be reconciled with a lack of significant cell death together with availability but impaired utilization of oxygen. In conjunction with the relatively rapid ability of the organ to recover in surviving patients, a paradigm of metabolic shutdown triggered by a decrease in mitochondrial energy production appears increasingly valid. This review discusses data demonstrating temporal changes in oxygen utilization through the septic process, evidence for mitochondrial derangements, and recovery of mitochondrial function preceding clinical recovery. Copyright © 2011 by Thieme Medical Publishers, Inc. Source


Vossenkamper A.,Blizard Institute | Lutalo P.M.K.,Rayne Institute | Spencer J.,Kings College London
Clinical and Experimental Immunology | Year: 2012

Systemic lupus erythematosus (SLE) and Sjögren's syndrome are autoimmune disorders which are characterized by a disturbed B cell homeostasis which leads ultimately to dysfunction of various organs. One of the B cell subsets that appear in abnormal numbers is the population of transitional B cells, which is increased in the blood of patients with SLE and Sjögren's syndrome. Transitional B cells are newly formed B cells. In mice, transitional B cells undergo selection checks for unwanted specificity in the bone marrow and the spleen in order to eliminate autoreactive B cells from the circulating naive B cell population. In humans, the exact anatomical compartments and mechanisms of the specificity check-points for transitional B cells remain unclear, but appear to be defective in SLE and Sjögren's syndrome. This review aims to highlight the current understanding of transitional B cells and their defects in the two disorders before and after B cell-targeted therapies. © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology. Source


Vargas-Hitos J.A.,systemIC | Ateka-Barrutia O.,Rayne Institute | Sangle S.,Rayne Institute | Khamashta M.A.,Rayne Institute
Annals of the Rheumatic Diseases | Year: 2011

Objective: Evaluation of the effectiveness and safety of long-term low molecular weight heparin (LMWH) in patients with antiphospholipid syndrome (APS) that had not previously responded to or tolerated oral vitamin K antagonists. Methods: 23 patients with confirmed diagnosis of APS were retrospectively recruited. All patients were receiving LMWH as a result of intolerance and/or lack of response to warfarin therapy. The type of LMWH, the duration of treatment, the reason for switching to LMWH and the adverse effects were recorded. Outcomes were classified as no improvement, partial improvement or total improvement after at least 1 year of using LMWH. Results: The average duration of LMWH treatment was 36 months. Most of the patients were on treatment with enoxaparin (n=16, 69%) and were switched to LMWH from warfarin mainly because of thrombosis despite therapeutic international normalised ratio (n=9, 39%). Good quality of life with no evidence of recurrent thrombotic events was noted in nine patients (39%), whereas 11 (48%) showed partial clinical improvement but no evidence of recurrent thrombotic episodes. Osteoporosis was reported in five patients (23%), all of whom were also receiving treatment with corticosteroids. Conclusions: Long-term LMWH may be a safe and effective alternative to warfarin for APS patients. Source

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