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      Preliminary Investigation of the Clinical Value of Vascular Endothelial Growth Factor and Hypoxia-Inducible Factor-1α in Pericardial Fluid in Diagnosing Malignant and Tuberculous Pericardial Effusion

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          Abstract

          Objectives: To investigate the clinical value of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) in diagnosing malignant and tuberculous pericardial effusion. Methods: Eighty patients with exudative pericardial effusion undergoing pericardiocentesis and drainage were divided into 2 groups, namely those with malignancy and those with tuberculosis. The levels of HIF-1α, VEGF, lactate dehydrogenase (LDH) and adenosine deaminase (ADA) in pericardial fluid and serum were measured. Routine and cytological examination of pericardial fluid, clinical characteristics and some blood parameters were compared between the 2 groups. Results: There were 33 patients with tuberculous pericardial effusion and 47 with malignant pericardial effusion. The levels of VEGF and HIF-1α in pericardial fluid in the malignancy group were significantly higher than those in the tuberculosis group (p < 0.01), and there was a moderate positive correlation between the levels of VEGF and HIF-1α (r = 0.79, p < 0.01). The sensitivity and specificity of combining VEGF and HIF-1α were 90.8 and 88.3%, respectively. The 2 groups showed no differences with regard to gender distribution, occurrence of fever, erythrocyte sedimentation rate or the levels of hemoglobin, LDH, ADA, serum HIF-1α and VEGF. Conclusions: Both VEGF and HIF-1α in pericardial fluid have determinative value in the differential diagnosis of malignant and tuberculous pericardial effusion.

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          Most cited references14

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          Tuberculous pericarditis.

          The incidence of tuberculous pericarditis is increasing in Africa as a result of the human immunodeficiency virus (HIV) epidemic. The primary objective of this article was to review and summarize the literature on the pathogenesis, diagnosis, and management of tuberculous pericarditis. We searched MEDLINE (January 1966 to May 2005) and the Cochrane Library (Issue 1, 2005) for information on relevant references. A "definite" diagnosis of tuberculous pericarditis is based on the demonstration of tubercle bacilli in pericardial fluid or on a histological section of the pericardium; "probable" tuberculous pericarditis is based on the proof of tuberculosis elsewhere in a patient with otherwise unexplained pericarditis, a lymphocytic pericardial exudate with elevated adenosine deaminase levels, and/or appropriate response to a trial of antituberculosis chemotherapy. Treatment consists of the standard 4-drug antituberculosis regimen for 6 months. It is uncertain whether adjunctive corticosteroids are effective in reducing mortality or progression to constriction. Surgical resection of the pericardium remains the appropriate treatment for constrictive pericarditis. The timing of surgical intervention is controversial, but many experts recommend a trial of medical therapy for noncalcific pericardial constriction, and pericardiectomy in nonresponders after 4 to 8 weeks of antituberculosis chemotherapy. Research is needed to improve the diagnosis, assess the effectiveness of adjunctive steroids, and determine the impact of HIV infection on the outcome of tuberculous pericarditis.
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            Regulation of angiogenesis by oxygen sensing mechanisms.

            The choices for blood vessels to undergo angiogenesis or stay quiescent are mostly determined by the status of tissue oxygenation. A major link between tissue hypoxia and active angiogenesis is the accumulation of hypoxia-inducible factor (HIF)-alpha subunits which play a major role in the transcriptional activation of genes encoding angiogenic factors. HIF-alpha abundance is negatively regulated by a subfamily of dioxygenases referred to as prolyl hydroxylase domain-containing proteins (PHDs) which use O(2) as a substrate to hydroxylate HIF-alpha subunits and hence tag them for rapid degradation. Under hypoxic conditions, HIF-alpha subunits accumulate due to reduced hydroxylation efficiency and form transcriptionally active heterodimers with HIF-1ss to activate the expression of angiogenic factors and other proteins important for cellular adaptation to hypoxia. Angiogenesis is regulated by a combination of at least two different mechanisms. The paracrine mechanism is mediated by non-endothelial expression of angiogenic factors such as vascular endothelial growth factor (VEGF)-A, which in turn interact with endothelial cell surface receptors to initiate angiogenic activities. In the autocrine mechanism, endothelial cell themselves are induced to express VEGF-A, which collaborate with the paracrine mechanism to support angiogenesis and protect vascular integrity. Because of critical roles of PHDs and HIFs in regulating angiogenic activities, studies are underway to assess their candidacy as targets for angiogenesis therapies.
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              Vascular endothelial growth factor in pleural effusions of different origin.

              This study aimed to determine the diagnostic relevance of vascular endothelial growth factor (VEGF) in the pleural fluid and serum of patients with pleural effusions of different aetiology. VEGF was quantified in the pleural effusion fluid and serum of 96 patients with malignancies (58 lung cancers (CA) and 38 tumours with secondaries to the lung (TM)), 45 with congestive heart failure (CHF), 28 with tuberculosis (TB), 45 with acute infections (INF), and in the serum of 20 healthy controls. VEGF pleural effusion concentrations were significantly different in the main diagnostic groups. VEGF was higher in effusions of patients with malignancies (CA as well as TM) in comparison with INF, TB or CHF. In serum, however, high VEGF concentrations indicated CA, TM or INF, but not TB or CHF. Despite significant differences of VEGF levels in different patient groups, receiver-operating characteristic analysis revealed insufficient diagnostic value of VEGF for differential diagnosis of pleural effusions. In conclusion, vascular endothelial growth factor serum concentration is highly suggestive of the presence of lung disease in general, except for tuberculosis. In effusion fluid, the presence of vascular endothelial growth factor clearly indicates inflammatory or malignant origin. However, for diagnostic use, additional parameters besides vascular endothelial growth factor are mandatory.
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                Author and article information

                Journal
                CRD
                Cardiology
                10.1159/issn.0008-6312
                Cardiology
                S. Karger AG
                0008-6312
                1421-9751
                2010
                June 2010
                27 April 2010
                : 116
                : 1
                : 37-41
                Affiliations
                aDepartment of Internal Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, bCentral Hospital of Wuhan, Wuhan, China; cDepartment of Internal Cardiology, University Hospital of Tuebingen, University of Tuebingen, Tuebingen, Germany
                Article
                313465 Cardiology 2010;116:37–41
                10.1159/000313465
                20424452
                9e38da23-79ee-48df-9a02-ebeb5cc1291d
                © 2010 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 16 November 2009
                : 29 January 2010
                Page count
                Tables: 2, References: 20, Pages: 5
                Categories
                Original Research

                General medicine,Neurology,Cardiovascular Medicine,Internal medicine,Nephrology
                Vascular endothelial growth factor,Tuberculous pericardial effusion,Malignant pericardial effusion,Hypoxia-inducible factor-1α

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