TY - BOOK T1 - Cardiovascular Medicine. Chapter 28 Global differences in atherosclerosis 653-658 A1 - Poole-Wilson, PA ED - Willerson JT, Cohn JN, Wellens HJJ, Holmes DR Y1 - 2007/// VL - 3rd PB - Springer-Verlag CY - London SN - 1-84628-188-1 SP - 1 EP - 2926 N2 - - L1 - http://springer.com ER - TY - BOOK T1 - Innovation in the Biopharmaceutical Industry A1 - Atun, R A A1 - Sheridan, DJ A1 - Attridge, J A1 - Sikora, K A1 - Harvey, I A1 - Wild, J A1 - Gurol-Urganci, I A1 - Kleyn, D A1 - Kitney , R ED - R A Atun and D J Sheridan Y1 - 2007/// PB - World Scientific Publishing Company CY - Singapore SN - 981-270-660-7 SP - 1 EP - 140 N2 - - ER - TY - BOOK T1 - Transplantation Immunology, Methods and Protocols A1 - Hornick,P Y1 - 2006/02// N2 - - ER - TY - BOOK T1 - Noninvasive Imaging of Myocardial Ischemis A1 - Anagnostopoulos CD A1 - Bax JJ A1 - Nihoyannopoulos P A1 - Van der Walls E ED - Anagnostopoulos CD, Baxx JJ, Nihoyannopoulos P, Van der Walls E. Y1 - 2006/// VL - 1 IS - 1 PB - Springer-Verlag London 2006 CY - London,UK SN - 1-84628-027-3 SP - 1 EP - 314 N2 - - ER - TY - BOOK T1 - Echocardiography in the heart made simple. A1 - Ho SY A1 - Rigby ML A1 - Anderson RH Y1 - 2005/07// PB - Imperial College Press CY - London UK SN - 1-86094-124-9 SP - 1 EP - 150 N2 - - ER - TY - BOOK T1 - NO-derived markers in exhaled breath condensate. New Perspectives in Monitoring Lung Inflammation. Analysis of exhaled breath condensate. A1 - Kharitonov SA ED - P Montuschi Y1 - 2005/// PB - CRC PRESS N2 - - ER - TY - BOOK T1 - Measurements of exhaled nitric oxide. Paediatric Pulmonary Function Testing. Progress in Respiratory Research. A1 - SA Kharitonov A1 - Kharitonov sa ED - J.Hammer, E.Eber Y1 - 2005/// IS - 33 PB - Karger SP - 166 EP - 180 N2 - - ER - TY - BOOK T1 - Exhaled breath markers in COPD. Progress in Inflammation Research. Recent advances in the pathophysiology of COPD. A1 - Barnes PJ A1 - Erin EM A1 - Hansel T A1 - Kharitonov SA A1 - Tan A ED - Clive P. Page and Peter J. Barnes Y1 - 2004/// N2 - - ER - TY - BOOK T1 - An Atlas of Chronic Obstructive Pulmonary Disease A1 - Hansel TT A1 - Barnes PJ Y1 - 2004/// PB - Parthernon Publishing CY - London SN - 1-84214-004-3 N2 - - ER - TY - BOOK T1 - RAPID REFERENCE Cardiovascular disease prevention. A1 - Wood D A1 - Kotseva K Y1 - 2004/// PB - Mosby, Elsevier Ltd N2 - - ER - TY - BOOK T1 - Recent Advances in the Pathophysiology of COPD. Progress in Inflammation Research. A1 - Hansel T ED - Hansel TT; Barnes PJ Y1 - 2004/// PB - Birkhauser CY - Basel, Boston, Berlin N2 - - ER - TY - BOOK T1 - Pharmacology and Therapeutics of Asthma and COPD A1 - Barnes PJ ED - Page CP; Barnes PJ Y1 - 2004/// PB - Springer CY - Berlin SN - 3-540-00464-5 SP - 1 EP - 376 N2 - - ER - TY - BOOK T1 - An Atlas of Chronic Obstructive Pulmonary Disease A1 - Hansel TT A1 - Barnes PJ Y1 - 2004/// PB - Parthenon Publishing CY - New York SN - 1-84214-004-3 SP - 1 EP - 290 N2 - - ER - TY - BOOK T1 - Allergens and Allergen Immunotherapy A1 - Till SJ A1 - Durham SR ED - RF Lockey, SC Bukantz and J Bousquet Y1 - 2004/// VL - 3rd PB - Marcel Dekker SN - 0824756509 N2 - - ER - TY - BOOK T1 - Hypertension A1 - Schachter M A1 - Monkman D Y1 - 2004/// PB - Elsevier Churchill Livingstone CY - Edinburgh SN - 0443 074704 SP - 1 EP - 134 N2 - - ER - TY - BOOK T1 - Complete Medicine and Surgery A1 - Kendall G A1 - Shiu KY A1 - Johnston SL Y1 - 2004/// PB - Blackwell Science N2 - - ER - TY - BOOK T1 - Cell Motility:from molecules to organisms A1 - Clark P ED - Ridley A; Peckham M; Clark P Y1 - 2004/01// PB - John Wiley and Sons CY - Chichester, England, UK SN - 0 470 84872 3 N2 - - ER - TY - BOOK T1 - Cough A1 - Morice A A1 - Bush A Y1 - 2003/// PB - Current Medical Literature N2 - - ER - TY - BOOK T1 - Recent Advances in the Pathophysiology of COPD A1 - Hansel T A1 - Barnes PJ ED - Hansel T; Barnes PJ Y1 - 2003/// PB - Birkhauser Verlag SP - 1 EP - 231 N2 - - ER - TY - BOOK T1 - Living with heart failure - a guide for patients A1 - Cowie MR Y1 - 2003/// PB - Bladon Medical Publishing CY - Chipping Norton, Oxfordshire SN - 1-904218-22-9 N2 - - ER - TY - BOOK T1 - The effective management of asthma. U.K. Key advances in clinical practice series A1 - Partridge MR ED - Partridge MR; Miles A Y1 - 2003/// PB - Aesculapius Medical Press SN - 1-9030-4426-X N2 - - ER - TY - BOOK T1 - Managing heart failure in primary care - a practical guide A1 - Cowie MR A1 - Kirby M Y1 - 2003/// PB - Bladon Medical Publishing SN - 1-904218-20-2 N2 - - ER - TY - BOOK T1 - Respiratory infections in allergy and asthma A1 - Johnston SL ED - Papadopoulos NG; Johnston SL Y1 - 2003/// PB - Marcell Dekker CY - New York N2 - - ER - TY - BOOK T1 - Asthma and COPD: basic mechanisms and clinical management A1 - Barnes PJ Y1 - 2002/// SN - 0-1207-9028-9 N2 - - ER - TY - BOOK T1 - Hypertension: A guide to assessment and management A1 - Poulter N A1 - Kirby M Y1 - 2002/// SN - 1-9042-1801-6 N2 - - ER - TY - BOOK T1 - Growing up with lung disease: the lung in transition to adult life A1 - Bush A A1 - Zach M A1 - Carlsen KH Y1 - 2002/// IS - 7 PB - ERS Monograph SN - 1-9040-9722-7 N2 - - ER - TY - BOOK T1 - Cardiovascular magnetic resonance A1 - Manning WJ A1 - Pennell DJ Y1 - 2002/// SN - 0-4430-7519-0 N2 - - ER - TY - BOOK T1 - Disease markers in exhaled breath A1 - Maczin N A1 - Kharitonov SA A1 - Yacoub MH A1 - Barnes PJ Y1 - 2002/// SN - 0-8247-0817-2 SP - 1 EP - 560 N2 - - ER - TY - BOOK T1 - Disease markers in exhaled breath A1 - Marczin N A1 - Kharitonov SA A1 - Yacoub MH A1 - Barnes PJ Y1 - 2002/// SN - 0-8247-0817-2 SP - 1 EP - 560 N2 - - ER - TY - BOOK T1 - Cardiovascular Magnetic Resonance A1 - Pennell DJ ED - Manning WJ; Pennell DJ Y1 - 2002/// PB - Churchill Livingstone SN - 0-443-07519-0 N2 - - ER - TY - BOOK T1 - Disease markers in exhaled breath A1 - Marczin N A1 - Kharitonov SA A1 - Yacoub MH A1 - Barnes PJ Y1 - 2002/// SN - 0-8247-0817-2 SP - 1 EP - 560 N2 - - ER - TY - BOOK T1 - Combination Therapy and Hypertension A1 - Schachter M Y1 - 2001/// PB - Taylor & Francis CY - London SN - 1-853-17732-6 N2 - - ER - TY - BOOK T1 - Shared care for hypertension A1 - Poulter N A1 - Thom S A1 - Kirby M Y1 - 2001/// SN - 1-8990-6680-2 N2 - - ER - TY - BOOK T1 - Human Airway Inflammation: Sampling techniques and analytical protocols A1 - Donnelly LE Y1 - 2001/// SN - 0-89603-923-4 N2 - - ER - TY - BOOK T1 - Managing chronic obstructive pulmonary disease A1 - Barnes PJ Y1 - 2001/// SN - 1-8587-3932-2 N2 - - ER - TY - BOOK T1 - Asthma: critical debates A1 - Johnston SL ED - Johnston SL; Holgate ST Y1 - 2001/// SN - 0-6320-5721-1 N2 - - ER - TY - BOOK T1 - New drugs for asthma, allergy and COPD A1 - Hansel T Y1 - 2001/// IS - 31 SN - 3-8055-6862-2 SP - 31 N2 - - ER - TY - BOOK T1 - New Drugs for Asthma, Allergy and COPD. Progress in Respiratory Research. A1 - Hansel T ED - Hansel TT; Barnes PJ Y1 - 2001/// IS - 31 PB - Karger CY - Basel SP - 31 N2 - - ER - TY - BOOK T1 - Human Airway Inflammation: Sampling techniques and analytical protocols A1 - Rogers DF ED - Rogers DF; Donnelly LE Y1 - 2001/// SN - 0-89603-923-4 N2 - - ER - TY - BOOK T1 - New drugs for asthma, allergy and COPD A1 - Barnes PJ Y1 - 2001/// IS - 31 SN - 3-8055-6862-2 N2 - - ER - TY - BOOK T1 - Shared care for hypertension A1 - Poulter N A1 - Thom S A1 - Kirby M Y1 - 2001/// SN - 1-8990-6680-2 N2 - - ER - TY - BOOK T1 - Allergy and allergic diseases: with a view to the future A1 - A.B. Kay (editor) Y1 - 2000/// IS - Br Med Bull 56 PB - Royal Society of Medicine Press Limited CY - London N2 - - ER - TY - BOOK T1 - Asthma & Rhinitis A1 - Till SJ A1 - Durham SR ED - William Busse and Stephen Holgate Y1 - 2000/// VL - 2nd PB - Blackwell Science Ltd SN - 0632041757 N2 - - ER - TY - BOOK T1 - Asthma and Allergic Diseases. Physiology, Immunopharmacology and Treatment A1 - G. Marone A1 - K.F. Austen A1 - S.T. Holgate A1 - A.B. Kay A1 - L.M. Lichtenstein (editors) Y1 - 1998/// PB - Academic Press CY - London SP - 1 EP - 439 N2 - - ER - TY - BOOK T1 - Allergy and Allergic Diseases A1 - A.B. Kay (editor) ED - A.B. Kay Y1 - 1997/// VL - 1st IS - volumes 1 and 2 PB - Blackwell Science CY - Oxford SN - 0-86542-867-0 SP - 1 EP - 1738 N2 - - ER - TY - CHAP T1 - The Heart and the kidney A1 - Cowie, MR ED - Willerson, JT, Cohn, JN, Wellens, HJJ, Holmes, DR Jr. T2 - Cardiovascular medicine Y1 - 2007/// VL - 3rd PB - Verlag CY - London SN - 1-84628-188-1 SP - 2819 EP - 2837 N2 - - ER - TY - CHAP T1 - The epidemiology and diagnosis of heart failure A1 - Dar, O A1 - Cowie, MR ED - Fuster, V T2 - Hurst's The Heart Y1 - 2007/// VL - 12th PB - Andover Publishing SP - 713 EP - 723 N2 - - ER - TY - CHAP T1 - Microbulles ciblees pour I'imagerie ultrasonore A1 - Sennoga, CA A1 - Yeh, JS A1 - Seddon, JM A1 - Nourshargh, S A1 - Eckersley, RJ A1 - Haskard, DO A1 - Cosgrove , DO A1 - Nihoyannopoulos, P ED - Tranquart F, Correreas J-M, Bouakaz A T2 - Echographie de Contraste Y1 - 2007/// PB - Springer CY - Paris SP - 321 EP - 328 N2 - - ER - TY - CHAP T1 - Acute respiratory distress syndrome A1 - SJ Finney A1 - G Bellingan ED - G Laurent, S Shapio T2 - Encyclopaedia of Respiratory Medicine Y1 - 2006/03// VL - 1 M2 - 1 PB - Academic Press CY - London SN - 0-12-438360-2 SP - 11 EP - 18 N2 - - ER - TY - CHAP T1 - Eotaxins A1 - Sabroe, I A1 - Williams, T.J A1 - Pease, J.E ED - Laurent, G. and Shapiro, S. T2 - Encyclopedia of Respiratory Medicine. Y1 - 2006/// PB - Elsevier SN - 0-12-438360-2 N2 - - ER - TY - CHAP T1 - Notch A1 - Boyton R ED - Laurent G L and Shapiro S T2 - Encyclopedia of Respiratory Medicine Y1 - 2006/// PB - Elsevier Limited CY - Oxford, UK N2 - - ER - TY - CHAP T1 - Pneumonia: Fungal A1 - Boyton R ED - Laurent G L and Shapiro S T2 - Encyclopedia of Respiratory Medicine Y1 - 2006/// PB - Elsevier Limited CY - Oxford, UK N2 - - ER - TY - CHAP T1 - Mechanosensitive-Mediated Interaction, Integration, and Cardiac Control. A1 - Max Lab ED - Samual Sideman, Rafael Bayer, Amir Landesberg. T2 - Interactive and Integrative Cardiology. Y1 - 2006/// PB - N. Y Academy of Science CY - New York SP - 282 EP - 300 N2 - - ER - TY - CHAP T1 - Lung Defence A1 - Boyton R ED - Laurent G L and Shapiro S T2 - Encyclopedia of Respiratory Medicine Y1 - 2006/// PB - Elsevier Limited CY - Oxford, UK N2 - - ER - TY - CHAP T1 - Proteinase inhibitors: Secretory Leukoprotease Inhibitor and Elafin. A1 - Tetley TD ED - Laurent GJ, Shapiro S T2 - Encyclopedia of Respiratory Medicine Y1 - 2006/// PB - Elsevier N2 - - ER - TY - CHAP T1 - Suprapontine control of breathing A1 - Moosavi, SH A1 - Paydarfar, D A1 - Shea, SA ED - Ward, DS; Dahan, A; Teppema, L T2 - Pharmacology and pathophysiology of the control of breathing Y1 - 2005/05/24/ M2 - 202 PB - Marcel Dekker CY - New York SN - 0824758900 N2 - - ER - TY - CHAP T1 - Palliative care in heart failure A1 - Gibbs LME A1 - Gibbs JSR ED - Watson M, Lucas C, Hoy A, Back I T2 - Oxford Handbook of Palliative Care Y1 - 2005/// PB - Oxford University Press Inc CY - New York SP - 585 EP - 588 N2 - - ER - TY - CHAP T1 - Epidemiology of dysglycaemia, diabetes and cardiovascular disease A1 - Wood DA A1 - Kotseva K ED - G Rosano T2 - Diabetes and Coronary Artery Disease Y1 - 2005/// PB - Wolters Kluwer Health, Adis Communications SP - 3 EP - 12 N2 - - ER - TY - CHAP T1 - Pulmonary arteriovenous malformations A1 - Shovlin CL ED - Haskard DO T2 - Horizons in Medicine Y1 - 2005/// M2 - 17 PB - RCP CY - London SN - 1-8601-6253-3 SP - 333 EP - 343 N2 - - ER - TY - CHAP T1 - Regional stretch effects in pathological myocardium. A1 - Lab Max J. ED - Peter Kohl, Frederick Sachs, Michael Franz T2 - Cardiac mechano-electric feedback and arrhythmias: from pipette to patient. Y1 - 2005/// VL - 1 M2 - 1 PB - Elsevier CY - Philadelphia SN - 1-4160-0034-8 SP - 108 EP - 118 N2 - - ER - TY - CHAP T1 - Antiprotease therapy. A1 - Tetley TD ED - Cazzola M, Celli B, Dahl R, Rennard S T2 - Therapeutic strategies in COPD. Y1 - 2005/// PB - Taylor & Francis CY - Oxford SN - 1904392423 SP - 233 EP - 246 N2 - - ER - TY - CHAP T1 - Cytokines and Chemokines in Airway Inflammation A1 - Suzanne L Traves ED - Paolo Montuschi T2 - New Perspectives in Monitoring Lung Inflammation Y1 - 2005/// PB - CRC Press CY - Florida, USA SN - 0-415-32465-3 SP - 183 EP - 209 N2 - - ER - TY - CHAP T1 - Risk scores for management and prevention of coronary heart disease. A1 - Wood D A1 - Kotseva K ED - M Marmot; P Elliott T2 - Coronary Heart Disease Epidemiology. From aetiology to public health. 2nd edition Y1 - 2005/// PB - Oxford University Press SP - 669 EP - 687 N2 - - ER - TY - CHAP T1 - Spirometry, an introduction A1 - Stephenson P A1 - Partridge M ED - Dr John Haughney T2 - A primary care guide to COPD Y1 - 2005/// PB - Magister Consulting Ltd CY - Dartford, Kent SN - 1 873839 61 8 SP - 25 EP - 35 N2 - - ER - TY - CHAP T1 - Pharmacological characterisation of embryonic stem cell-derived cardiomyocyte cultures A1 - Ali, N N A1 - Brito-Martins, M A1 - Gorelik, J A1 - Xu, X A1 - Korchev, Y A1 - Zhu, H A1 - Poole-Wilson, P A A1 - Fuller, S J A1 - Harding, S E ED - Habib, N., Gordon, M.Y., Levicar, N. and Jiao, L. T2 - Stem Cells:Repair and Regeneration Y1 - 2005/// PB - Imperial College Press CY - London SP - 139 EP - 147 N2 - - ER - TY - CHAP T1 - Mechanoelectric Transduction/Feedback: Physiology and Pathophysiology A1 - Max Lab ED - Matti Weckstrom and Pasi Tavi T2 - Cardiac Mechanotransduction Y1 - 2005/// VL - 1 M2 - 1 PB - Eureka N2 - - ER - TY - CHAP T1 - The pore of the ryanodine receptor channel A1 - Williams AJ A1 - Chen SRW A1 - Welch W ED - Wehrens XHT; Marks AR T2 - RYANODINE RECEPTORS Structure, function and dysfunction in clinical disease Y1 - 2005/// PB - Springer CY - New York SN - 0-387-23187-0 SP - 43 EP - 52 N2 - - UR - http://www.springeronline.com ER - TY - CHAP T1 - Pulmonary arteriovenous malformations and other pulmonary vascular abnormalities A1 - Shovlin CL A1 - Jackson JE A1 - Hughes JMB ED - Mason, Broaddus, Murray, Nadel T2 - Murray and Nadel's textbook of Respiratory Medicine Y1 - 2005/// VL - 4th M2 - 2 PB - Elsevier Saunders CY - Pennsylvania SN - 0-7216-0327-0 SP - 1480 EP - 1501 N2 - - ER - TY - CHAP T1 - Non-viral vectors for gene therapy A1 - Davies JC A1 - Alton EWFW ED - Huang L, Hung MC and Wagner E T2 - Airway gene therapy. Y1 - 2005/// VL - 2 M2 - 2 SP - 291 EP - 314 N2 - - ER - TY - CHAP T1 - Presentation, diagnosis and differential diagnosis A1 - Stephenson P A1 - Partridge M ED - Dr John Haughney T2 - A primary care guide to COPD Y1 - 2005/// PB - Magister Consulting Ltd CY - Dartford, Kent SN - 1 873839 61 8 SP - 1 EP - 11 N2 - - ER - TY - CHAP T1 - Domiciliary oxygen A1 - Partridge M ED - Dr John Haughney T2 - A primary care guide to COPD Y1 - 2005/// PB - Magister Consulting Ltd CY - Dartford, Kent SN - 1 873839 61 8 SP - 124 EP - 134 N2 - - ER - TY - CHAP T1 - Lung Function and Exercise Testing A1 - Bush A A1 - Rosenthal M ED - Anderson RH, Baker EJ, Macartney F, Rigby ML, Shinebourne EA, Tynan M T2 - Paediatric Cardiology Y1 - 2005/// M2 - 2nd PB - Churchill Livingstone SN - 0-4430-7990-0 SP - 593 EP - 618 N2 - - ER - TY - CHAP T1 - Mechanically Mediated Crosstalk in Heart. A1 - Max Lab ED - Andre Kamkin and Irina Kiseleva T2 - Mechanosensitivity in Cells and Tissues Y1 - 2005/// VL - 1 M2 - 1 PB - Academia CY - Moscow N2 - - ER - TY - CHAP T1 - Self management education in COPD A1 - Partridge M ED - Dr John Haughney T2 - A primary care guide to COPD Y1 - 2005/// PB - Magister Consulting Ltd CY - Dartford, Kent SN - 1 873839 61 8 SP - 96 EP - 106 N2 - - ER - TY - CHAP T1 - Definitions of Chronic Obstructive Pulmonary Disease A1 - Pride NB ED - Pauwels RA; Postma DS; Weiss ST. T2 - Long-term intervention in Chronic Obstructive Pulmonary Disease Y1 - 2004/09// PB - Dekker SN - 0 8247 5438 7 SP - 1 EP - 13 N2 - - ER - TY - CHAP T1 - Nebulizers in cystic fibrosis and non-CF bronchiectasis in children and adults A1 - Bush A A1 - Suri R A1 - Webb AK ED - Boe J, O'Driscoll R, Dennis JH T2 - Practical Handbook of Nebulizer Theory Y1 - 2004/// PB - Martin Dunitz CY - London SP - 137 EP - 162 N2 - - ER - TY - CHAP T1 - Coronary Heart Disease A1 - Wood DA A1 - Kotseva KP A1 - Fox K A1 - Bakhai A A1 - Bowker TJ ED - Stevens A; Raftery J; Mant J; Simpson S T2 - Health Care Needs Assessment . The epidemiologically based needs assessment reviews. 1st Series, 2nd Edition Y1 - 2004/// M2 - Vol 1, Chapter 5 PB - Radcliffe Publishing Ltd SP - 373 EP - 448 N2 - - ER - TY - CHAP T1 - Parainfluenza viruses A1 - Psarras S A1 - Papadopoulos NG A1 - Johnston SL ED - Zuckerman, Banatvala, Griffiths, Pattison and Schoub T2 - Principles and Practice of Clinical Virology Fifth Edition Y1 - 2004/// PB - John Wiley & Son CY - UK SP - 299 EP - 321 N2 - - ER - TY - CHAP T1 - Overview of Airway Mucus Clearance A1 - Rogers DF ED - Rubin BK, van der Schans CP T2 - Therapy for Mucus-Clearance Disorders Y1 - 2004/// PB - Marcel Dekker CY - New York SN - 0-8247-0716-8 SP - 1 EP - 27 N2 - - ER - TY - CHAP T1 - Left Heart Disease and the Pulmonary Circulation A1 - Gibbs JSR A1 - Henein MY ED - Peacock A, Rubin LJ T2 - Pulmonary Circulation Diseases and Their Treatment Y1 - 2004/// PB - Arnold CY - London SP - 346 EP - 355 N2 - - ER - TY - CHAP T1 - HRT and SERMs. A1 - Stevenson JC ED - Woolf AD, Akesson K, Adami S. T2 - The Year Book in Osteoporosis. Y1 - 2004/// PB - Clinical Publishing CY - Oxford SP - 225 EP - 246 N2 - - ER - TY - CHAP T1 - Nebulized antibiotics in cystic fibrosis and non-CF bronchiectasis in children and adults A1 - Webb AK A1 - Dodd ME A1 - Bush A ED - Boe J, O'Driscoll R, Dennis JH T2 - Practical Handbook of Nebulizer Theory Y1 - 2004/// PB - Martin Dunitz CY - London SP - 115 EP - 136 N2 - - ER - TY - CHAP T1 - Asthma: Clinical features, Diagnosis and Treatment A1 - Partridge MR ED - Albert RK, Spiro SG and Jett JR T2 - Clinical Respiratory Medicine Y1 - 2004/// PB - Mosby CY - Philadelphia SN - 0-323-02497-1 SP - 889 N2 - - ER - TY - CHAP T1 - Computed tomography (CT) scans in COPD A1 - Tennant RC A1 - Hansel TT A1 - Hansell DM T2 - Recent Advances in the Pathophysiolgy of COPD. Progress in Inflammatory Research. Y1 - 2004/// PB - Birkhauser CY - Basel, Boston, Berlin N2 - - ER - TY - CHAP T1 - Mechanoelectric Feedback/Transduction : Prevalence and Pathophysiology. A1 - Lab MJ ED - Zipes DP Jalliffe J. T2 - Cardiac Electrophysiology From Cell to Bedside Y1 - 2004/// PB - Saunders CY - Philadelphia SN - 0-7216-0323-8 SP - 242 N2 - - ER - TY - CHAP T1 - The influence of genetic factors on leucocyte and endothelial cell adhesion molecules A1 - Rao RM A1 - Russell AI A1 - Vyse T A1 - Haskard DO ED - Wilkins MR T2 - Cardiovascular Pharmacogenetics Y1 - 2004/// PB - Springer-Verlag SN - 3-540-40204-7 SP - 323 N2 - - ER - TY - CHAP T1 - Lipids partition caveolin-1 from ER membranes into lipid droplets: updating the model of lipid droplet biogenesis. A1 - Severs, N.J A1 - Shotton, D.M. ED - Celis, J.E. T2 - Cell Biology: A Laboratory Handbook Y1 - 2004/// VL - 3rd PB - Academic Press CY - San Diego SN - 0-12-164714-5 N2 - - ER - TY - CHAP T1 - Evaluation of New Drugs for Asthma and COPD: Endpoints, Biomarkers and Clinical Trial Designs A1 - Barnes PJ A1 - Erin EM A1 - Hansel TT A1 - Kharitonov S A1 - Tan AJ A1 - Tennant RC T2 - Pharmacology and Therapeutics of Asthma and COPD Y1 - 2004/// PB - Springer-Verlag CY - Heidelberg N2 - - ER - TY - CHAP T1 - Heart, Renal and Liver Failure A1 - Gibbs LME A1 - Gibbs JSR ED - Sykes N, Edmonds P, Wiles J T2 - Management of Advanced Disease Y1 - 2004/// VL - 4th PB - Arnold CY - London SP - 359 EP - 388 N2 - - ER - TY - CHAP T1 - New drugs for COPD based on advances in pathology A1 - Hansel TT A1 - Tennant RC A1 - Erin EM A1 - Tan AJ A1 - Barnes PJ T2 - Recent Advances in the Pathophysiology of COPD. Progress in Inflammation Research Y1 - 2004/// PB - Birkhauser CY - Basel, Boston, Berlin N2 - - ER - TY - CHAP T1 - Pulmonary arteriovenous malformations and aneurysms A1 - Shovlin CL A1 - Jackson JE ED - Gibson J, Geddes D, Costabel U, Sterk and Corrin T2 - Respiratory Medicine Y1 - 2004/// VL - 3rd PB - Harcourt Brace CY - London SP - 1773 EP - 1788 N2 - - ER - TY - CHAP T1 - Case study of BHOPAL incident A1 - Cullinan P ED - Tetsuo Satoh, Salmaan H. Inayat-Hussain T2 - Encyclopedia of Life Support Systems (EOLSS) Y1 - 2004/// PB - Eolss Publishers CY - Oxford, UK N2 - - ER - TY - CHAP T1 - HIV associated pneumonia in intensive care A1 - Boyton RJ A1 - Mitchell D A1 - Kon OM ED - Griffiths M and Evans T T2 - Respiratory Management in Critical Care Y1 - 2004/// PB - BMJ Publishing Group CY - London, UK SP - 120 EP - 124 N2 - - ER - TY - CHAP T1 - Pulmonary arteriovenous malformations A1 - Shovlin CL A1 - Jackson JE ED - AJ Peacock and LJ Rubin T2 - Pulmonary circulation Y1 - 2004/// VL - 2 PB - Edward Arnold Publishers CY - London SN - 0340807822 SP - 584 EP - 599 N2 - - ER - TY - CHAP T1 - Rhinoviruses A1 - Papadopoulos NG A1 - Johnston SL ED - Zuckerman, Banatvala, Griffiths, Pattison and Schoub T2 - Principles and Practice of Clinical Virology Fifth Edition Y1 - 2004/// PB - John Wiley & Son CY - UK N2 - - ER - TY - CHAP T1 - Mucus Hypersecretion in COPD A1 - Rogers DF ED - TT Hansel PJ Barnes T2 - Recent Advances in Pathophysiology of COPD Y1 - 2004/// SN - 3-7643-6914-0 SP - 101 EP - 119 N2 - - ER - TY - CHAP T1 - Asthma: Self management plans and patient education A1 - Barlow A A1 - Partridge MR ED - Scadding G and O'Connor B T2 - Key Advances in the Clinical Management of Asthma 2 Y1 - 2004/// PB - The Royal Society of Medicine Press Ltd CY - London SN - 1-8531-5561-6 SP - 35 EP - 40 N2 - - ER - TY - CHAP T1 - Heart disease A1 - Addington-Hall JM A1 - Rogers AE A1 - McCoy ASM A1 - Gibbs JSR ED - Morrison RS, Meier D, Capello C T2 - Geriatric Palliative Care Y1 - 2003/// PB - Oxford University Press CY - New York SP - 110 EP - 122 N2 - - ER - TY - CHAP T1 - Increasing adherence to therapy through modifying the doctor/patient interaction A1 - Partridge MR ED - Partridge MR and Miles A T2 - The effective management of asthma. UK Key advances in clinical practice Series Y1 - 2003/// PB - Aesculapius Medical Press CY - London SN - 1-9030-4426-X SP - 89 EP - 100 N2 - - ER - TY - CHAP T1 - Autonomic functions or the extrapyramidal system A1 - Schachter M ED - JK Aronson T2 - Side effects of drugs annual Y1 - 2003/// PB - Elsevier CY - Amsterdam SN - 0-444-50999-2 SP - 156 EP - 167 N2 - - ER - TY - CHAP T1 - Treatment of the Common Cold: prospects and implications for the treatment of asthma exacerbations A1 - Creer DD A1 - Gelder CM A1 - Johnston SL ED - Papadopoulos NG, Johnston SL; T2 - Respiratory infections in allergy and asthma Y1 - 2003/// PB - Marcell Dekker CY - New York SP - 675 EP - 710 N2 - - ER - TY - CHAP T1 - Nuclaer imaging in coronary artery disease A1 - Rahman SL A1 - Underwood SR ED - Wheatley DJ T2 - Surgery of coronary artery disease, second edition Y1 - 2003/// PB - Arnold CY - London SP - 84 EP - 97 N2 - - UR - http://www.arnoldpublishers.com ER - TY - CHAP T1 - Asthma: communication and education A1 - Partridge MR ED - Gibson GJ, Geddes DM, Costabel U, Sterk PJ, Corrin B T2 - Respiratory Medicine Y1 - 2003/// M2 - 3rd PB - Saunders SN - 0-7020-2613-1 SP - 1357 EP - 1367 N2 - - ER - TY - CHAP T1 - Pulmonary Gene Therapy A1 - Davies A1 - Geddes A1 - Alton ED - Rolland & Sullivan T2 - Pharmaceutical Gene Delivery Systems Y1 - 2003/// PB - Marcel Dekker Inc. CY - New York SN - 0-8247-4235-4 SP - 363 EP - 396 N2 - - ER - TY - CHAP T1 - Physiological considerations: biochemistry and cellular physiology of heart muscle A1 - Sugden PH A1 - Severs NJ A1 - MacLeod KT A1 - Poole-Wilson PA ED - Warrell DA; Cox TM; Firth JD; Benz EJ Jr T2 - Oxford Textbook of Medicine Y1 - 2003/// M2 - Vol 2 Chapter 15.1.3.1 PB - Oxford University Press CY - Oxford SP - 809 EP - 820 N2 - - ER - TY - CHAP T1 - Cystic Fibrosis A1 - Geddes D A1 - Bush A ED - Warrel D, Cox TM, Firth JD, Benz EJ T2 - Oxford Textbook of Medicine, 4th Edition Y1 - 2003/// SP - 1428 EP - 1438 N2 - - ER - TY - CHAP T1 - Viral Infections: Effects on nasal and lower airway functions A1 - Hussain I A1 - Johnston SL ED - Corren J; Togias A; Bousquet J T2 - Upper and Lower Respiratory Disease Y1 - 2003/// PB - Marcel Dekker, Inc CY - New York N2 - - ER - TY - CHAP T1 - Childhood Asthma Syndromes A1 - Bush A A1 - Price JP ED - Gibson GJ, Geddes DM, Costabel U, Sterk P, Corrin B T2 - Respiratory Medicene 3rd Edition Y1 - 2003/// PB - Saunders SP - 1396 EP - 1420 N2 - - ER - TY - CHAP T1 - Rare Lung Disease A1 - Bush A ED - McIntosh N, Helms P, Smyth R T2 - Forfar and Arneil's Textbook of Paediatrics, 6th Edition Y1 - 2003/// SP - 801 EP - 804 N2 - - ER - TY - CHAP T1 - Patient Education and Delivery of Care A1 - Partridge MR ED - Chung F, Fabbri LM T2 - Asthma: A European Respiratory Monograph Y1 - 2003/// PB - European Respiratory Society SN - 1-9040-9726-X SP - 449 EP - 458 N2 - - ER - TY - CHAP T1 - Chap 15.1.3.1 Biochemistry and cellular physiology of heart muscle A1 - Sugden PH A1 - Severs NJ A1 - MacLeod KT A1 - Poole-Wilson PA ED - Warrell DA, Cox TM, Firth JD and Benz EJ Jr T2 - Oxford Textbook of Medicine 4th Ed Y1 - 2003/// PB - Oxford University Press SP - 809 EP - 820 N2 - - ER - TY - CHAP T1 - Biochemistry and cellular physiology of heart muscle A1 - Sugden PH A1 - Severs NJ A1 - MacLeod KT A1 - Poole-Wilson PA ED - Warrell DA; Cox TM; Firth JD; Benz EJJ T2 - Oxford textbook of medicine Y1 - 2003/// PB - Oxford University Press SN - 0-19-262922-0 SP - 809 EP - 819 N2 - - ER - TY - CHAP T1 - Biochemistry and cellular physiology of heart muscle. A1 - Sugden PH A1 - Severs NJ A1 - MacLeod KT A1 - Poole-Wilson PA ED - Warrell DA, Cox TM, Firth JD with Benz EJ Jr T2 - Oxford Textbook of Medicine 4th edn Y1 - 2003/// PB - Oxford University Press CY - Oxford SN - 0-19-262922-0 SP - 809 EP - 820 N2 - - ER - TY - CHAP T1 - Malformations A1 - Bush A ED - Gibson GJ, Geddes DM, Costabel U, Sterk P, Corrin B T2 - Respiratory Medicene 3rd Edition Y1 - 2003/// PB - Saunders SP - 613 EP - 636 N2 - - ER - TY - CHAP T1 - Adult Congenital Heart Disease A1 - Philip J Kilner ED - Charles B iggins and Albert de Roos T2 - Cardiovascular MRI and MRA Y1 - 2003/// PB - Lippincott Williams and Wilkins CY - Philadelphia SN - 0 7817 3482 7 SP - 353 EP - 368 N2 - - ER - TY - CHAP T1 - Evidence Based Reccomendations for Primary Care A1 - Valiulis A A1 - Narkeviciute I A1 - Dumcius S A1 - Bush A A1 - Thomson A A1 - Usonis V A1 - Kaltenis P A1 - Vingras A A1 - Zilinskaite V ED - Valiulis A T2 - Lithuanian Paediatric Pneumonia Guidelines Y1 - 2003/// PB - Atkula CY - Vilnius N2 - - ER - TY - CHAP T1 - Communicating junctions, connexins and the cardiomyocyte: from cell biology to cardiology A1 - Severs NJ ED - Singal PK; Dixon IMC; Kirshenbaum LA; Dhalla NS T2 - Cardiac Remodeling and Failure Y1 - 2003/// PB - Kluwer Academic Publishers CY - Boston SN - 1-4020-7177-9 SP - 417 EP - 434 N2 - - ER - TY - CHAP T1 - Congenital Lung Disease A1 - Bush A ED - McIntosh N, Helms P, Smyth R T2 - Forfar and Arneil's Textbook of Paediatrics, 6th Edition Y1 - 2003/// SP - 787 EP - 793 N2 - - ER - TY - CHAP T1 - 47.4 Pathophysiology of chronic obstructive pulmonary disease A1 - Stanescu DC A1 - Pride NB ED - Gibson GJ; Geddes D; Costabel U; Sterk PJ; Corrin B. T2 - Respiratory Medicine Y1 - 2003/// M2 - 3rd Edition. Vol 2, part G Air PB - Saunders SN - 0-7020-2613-1 SP - 1154 EP - 1170 N2 - - ER - TY - CHAP T1 - Infektionen A1 - Schwarze J ED - Paul K T2 - Asthma bronchiale bei Kindern und Jugendlichen Y1 - 2003/// PB - Wissenschaftliche Verlagsgesellschaft mbH CY - Stuttgart, Germany SN - 3-8047-1910-4 SP - 52 EP - 57 N2 - - ER - TY - CHAP T1 - Public health and transport policy A1 - MacNeill S A1 - Cullinan P ED - Julian Hine, John Preston T2 - Integrated futures and transport choices. UK Transport Policy Beyond the 1998 White Paper and Transport Acts Y1 - 2003/// PB - Ashgate Publishing Ltd CY - Aldershot SP - 13 EP - 41 N2 - - ER - TY - CHAP T1 - Human leucocyte antigen (HLA) transgenic mice for the analysis of autoimmune disease A1 - Altmann DM A1 - Ellmerich S A1 - Boyton RJ ED - Friedland J and Lightstone E T2 - Infection and Immunity Y1 - 2003/// PB - Harwood Academic Publishers CY - Reading, UK SP - 3 EP - 14 N2 - - ER - TY - CHAP T1 - Lung Mechanics A1 - Pride NB A1 - Milic-Emili J ED - Calverley PMA; MacNee W; Pride NB; Rennard SI. T2 - Chronic Obstructive Pulmonary Disease Y1 - 2003/// M2 - 2nd PB - Arnold SN - 0 340 80718 0 SP - 151 EP - 174 N2 - - ER - TY - CHAP T1 - Cystic Fibrosis A1 - Bush A T2 - European Lung White Book Y1 - 2003/// PB - European Respiratory Society SP - 89 EP - 95 N2 - - ER - TY - CHAP T1 - Molecular mechanisms of respiratory virus-induced inflammation A1 - Papi A A1 - Caramori G A1 - Bellettato CM A1 - Adcock I A1 - Johnston SL ED - Papadopoulos NG; Johnston SL T2 - Respiratory infections in allergy and asthma Y1 - 2003/// PB - Marcell Dekker CY - New York SP - 199 EP - 228 N2 - - ER - TY - CHAP T1 - Cardiovascular Magnetic Resonance Imaging A1 - Philp J Kilner ED - Michael A Gatzoulis, Gary D Webb and Piers EF Daubeney T2 - Diagnosis and management of adult congenital heart disease Y1 - 2003/// VL - 1st PB - hurchill Livingstone SN - 0 443 07103 9 SP - 49 EP - 56 N2 - - ER - TY - CHAP T1 - Cystic Fibrosis A1 - Jaffe A A1 - Bush A T2 - Medicines for Children Y1 - 2003/// PB - RCPCH N2 - - ER - TY - CHAP T1 - Detection of Respiratory Viruses A1 - Taylor P A1 - Johnston SL ED - Gibson GJ; Geddes DM; Costabel U; Sterk PJ; Corrin B T2 - Respiratory Medicine Third Edition Y1 - 2003/// PB - Elsevier Science Limited CY - London SP - 385 EP - 390 N2 - - ER - TY - CHAP T1 - Therapeutic intervention to prevent coronary heart disease and stroke A1 - Sever P ED - Weber,Jonanthan T2 - Horizons in Medicine 15 Y1 - 2003/// PB - Royal College of Physicians of London CY - London SN - 1 86016 196 0 SP - 263 EP - 272 N2 - - ER - TY - CHAP T1 - Treatment of Respiratory Viruses A1 - Mallia P A1 - Johnston SL ED - Weber J T2 - Horizons in Medicine - Updates in Major Clinical Advances Y1 - 2003/// PB - Royal College of Physicians CY - London UK SP - 145 EP - 152 N2 - - ER - TY - CHAP T1 - Cystic Fibrosis in Childhood A1 - Bush A A1 - Davies JC ED - Gibson GJ, Geddes DM, Costabel U, Sterk P, Corrin B T2 - Respiratory Medicene 3rd Edition Y1 - 2003/// PB - Saunders SP - 1477 EP - 1494 N2 - - ER - TY - CHAP T1 - Regulation of Eosinophil Trafficking in Asthma and Allergy A1 - Pease, J. E. A1 - Weller, C.L. A1 - Williams, T.J. ED - Murphy, P.M. and Horuk, R. T2 - Chemokine Roles in Immunoregulation and Disease. Y1 - 2003/// VL - Chapter 7 PB - Springer SN - 3-540-40221-7 N2 - - ER - TY - CHAP T1 - Cystic Fibrosis in Childhood A1 - A Bush A1 - J Davies ED - Gibson, Geddes, Costabel, Sterk, Corrin T2 - Respiratory Medicine Y1 - 2003/// PB - Saunders SN - 0 7020 2613 1 SP - 1477 EP - 1494 N2 - - ER - TY - CHAP T1 - Macrolides as Biologic Response Modifiers in cystic Fibrosis and Bronchiectasis A1 - Bush A A1 - Rubin BK T2 - Sem Resp Crit Care Med Y1 - 2003/// SP - 737 EP - 747 N2 - - ER - TY - CHAP T1 - Animal models of allergen and virus-induced asthma A1 - Schwarze J A1 - Gelfand EW ED - Johnston SL; Papadopoulos NG T2 - Respiratory Infections in Allergy and Asthma Y1 - 2003/// PB - Marcel Dekker CY - New York SN - 0-8247-4126-9 SP - 329 EP - 363 N2 - - ER - TY - CHAP T1 - Animal models of viral respiratory infections A1 - Boyton RJ A1 - Openshaw PJ ED - Johnston S L and Papadopoulos N G T2 - Respiratory infections in allergy and asthma Y1 - 2003/// PB - Marcel Dekker, Inc. CY - New York, USA SP - 279 EP - 298 N2 - - ER - TY - CHAP T1 - Pathophysiology of sepsis: Role of nitric oxide A1 - Evans TW A1 - Finney SJ ED - Vincent JL, Carlet J, Opal S T2 - The Sepsis Text Y1 - 2002/02// PB - Kluwer Academic Publishers SN - 079237620X SP - 211 EP - 230 N2 - - ER - TY - CHAP T1 - Methods for flow management A1 - Gatehouse P A1 - Firmin D T2 - Handbook of cardiovascular magnetic resonance imaging Y1 - 2002/// SN - 3-7985-1285-X SP - 25 EP - 30 N2 - - ER - TY - CHAP T1 - Coronary artery disease A1 - Gibbs JSR T2 - Aviation medicine and the airline passenger: medical assessment and in-flight medical support Y1 - 2002/// SN - 0-3408-0637-0 SP - 99 EP - 106 N2 - - ER - TY - CHAP T1 - Infections A1 - Message SD A1 - Johnston SL T2 - Asthma and COPD: basic mechanisms and clinical management Y1 - 2002/// SN - 0-1207-9028-9 SP - 407 EP - 420 N2 - - ER - TY - CHAP T1 - Hormone replacement therapy and the postmenopausal cardiovascular system: metabolic basis and clinical implications A1 - Stevenson JC T2 - The effective management of the menopause Y1 - 2002/// SN - 1-9030-4424-3 SP - 23 EP - 25 N2 - - ER - TY - CHAP T1 - Drugs affecting autonomic functions of the extrapyramidal system A1 - Schachter M T2 - Side effects of drugs annual 25 Y1 - 2002/// SN - 0-4445-0674-8 SP - 166 EP - 174 N2 - - ER - TY - CHAP T1 - Respiratory A1 - Davies J ED - Beattie & Champion T2 - Essential Revision Notes in Paediatrics for the MRCPCH Y1 - 2002/// PB - PasTest SN - 1 901198 64 2 SP - 663 EP - 703 N2 - - ER - TY - CHAP T1 - Cystic Fibrosis in Adolescence A1 - Bush A A1 - Geddes DM ED - Bush A, Zach M, Carlsen K-H T2 - Growing up with lung disease: the lung in transition to adult life Y1 - 2002/// PB - European Respiratory Monograph SP - 225 EP - 253 N2 - - ER - TY - CHAP T1 - Regulation of leukocyte traffic to the lung A1 - Lloyd CM A1 - Gutierrez-Ramos JC ED - Lambrecht B, Hoogsteden HC & Diamant Z T2 - Immunologic Basis of Asthma Y1 - 2002/// PB - Humana Press SP - 406 EP - 438 N2 - - ER - TY - CHAP T1 - Impact of sleep on ventilation A1 - Morrell MJ A1 - Dempsey JA T2 - Breathing disorders in sleep Y1 - 2002/// SN - 0-7020-2510-0 SP - 3 EP - 17 N2 - - ER - TY - CHAP T1 - Neural and humoral control A1 - Barnes PJ T2 - Asthma and COPD: basic mechanisms and clinical management Y1 - 2002/// SN - 0-1207-9028-9 SP - 323 EP - 340 N2 - - ER - TY - CHAP T1 - New approaches in the treatment of hypertension A1 - Schachter M ED - N Kaplan, M Schachter T2 - New frontiers in hypertension Y1 - 2002/// PB - Lippincott Williams and Wilkins CY - London SN - 0-781-74155-6 SP - 101 EP - 113 N2 - - ER - TY - CHAP T1 - Vascular biology of hypertension A1 - Schachter M ED - BJ, Hunt, L Poston, M Schachter, AW Halliday T2 - An Introduction to vascular biology Y1 - 2002/// PB - Cambridge University Press CY - Cambridge SN - 0-521-79652-0 N2 - - ER - TY - CHAP T1 - Allergen-specific immunotherapy A1 - Kay AB A1 - Larche M T2 - Biotherapeutic approaches to asthma Y1 - 2002/// SN - 0-8247-0785-0 SP - 305 EP - 326 N2 - - ER - TY - CHAP T1 - Pulmonary physiology A1 - Pride NB T2 - Asthma and COPD: basic mechanisms and clinical management Y1 - 2002/// SN - 0-1207-9028-9 SP - 43 EP - 56 N2 - - ER - TY - CHAP T1 - The growing lung: normal development, and the long-term effects of pre- and post-natal insults A1 - Rosenthal M A1 - Bush A ED - Bush A, Zach M, Carlsen K-H T2 - Growing up with lung disease: the lung in transition to adult life Y1 - 2002/// PB - European Respiratory Monograph SP - 1 EP - 24 N2 - - ER - TY - CHAP T1 - What are the mechanisms of corticosteroids resistance in asthma? A1 - Barnes PJ T2 - Asthma: Critical debates Y1 - 2002/// SN - 0-6320-5721-1 SP - 241 EP - 254 N2 - - ER - TY - CHAP T1 - Biology of asthma A1 - Barnes PJ T2 - Disease markers in exhaled breath: Basic mechanisms and clinical applications Y1 - 2002/// SN - 1-5860-3273-9 SP - 133 EP - 142 N2 - - ER - TY - CHAP T1 - Should drugs affecting mucus properties be used in COPD? Clinical evidence A1 - Nightingale JA A1 - Rogers DF ED - T Similowski et al T2 - Clinical management of chronic obstructive pulmonary disease Y1 - 2002/// SN - 0-8247-0610-2 SP - 405 EP - 425 N2 - - ER - TY - CHAP T1 - Pathogenesis of COPD A1 - Rennard SI A1 - Barnes PJ T2 - Asthma and COPD: basic mechanisms and clinical management Y1 - 2002/// SN - 0-1207-9028-9 SP - 361 EP - 379 N2 - - ER - TY - CHAP T1 - Cytokines in asthma and COPD A1 - Chung KF T2 - Asthma and COPD Y1 - 2002/// SN - 0-1207-9028-9 SP - 261 EP - 271 N2 - - ER - TY - CHAP T1 - Heart disease A1 - Gibbs JSR Y1 - 2002/// SN - 0-1926-2960-3 SP - 30 EP - 43 N2 - - ER - TY - CHAP T1 - Molecular biology and cardiac development A1 - Barton PJR A1 - Moorman AFM ED - Anderson RH; Baker EJ; Shinebourne EA; Rigby ML; Tynan M. T2 - Paediatric Cardiology Y1 - 2002/// M2 - 2nd PB - Churchill Livingstone CY - London SN - 0-4430-7990-0 SP - 215 EP - 233 N2 - - ER - TY - CHAP T1 - Gap junctions and connexin expression in human heart disease A1 - Severs NJ ED - De Mello WC; Janse M T2 - Heart cell coupling and impulse propagation in health and disease Y1 - 2002/// PB - Kluwer Academic Publishers CY - Boston SN - 1-4020-7182-5 SP - 321 EP - 334 N2 - - ER - TY - CHAP T1 - Stress CMR - wall motion A1 - Pennell DJ T2 - Cardiovascular Magnetic Resonance Y1 - 2002/// SN - 0-4430-7519-0 SP - 113 EP - 133 N2 - - ER - TY - CHAP T1 - Drugs affecting autonomic functions or the extrapyramidal system A1 - Schachter M ED - JK Aronson T2 - Side effects of drugs annual Y1 - 2002/// PB - Elsevier CY - Amsterdam SN - 0-444-50674-8 SP - 166 EP - 174 N2 - - ER - TY - CHAP T1 - Corticosteroids A1 - Barnes PJ T2 - Asthma and COPD: basic mechanisms and clinical management Y1 - 2002/// SN - 0-1207-9028-9 SP - 547 EP - 564 N2 - - ER - TY - CHAP T1 - Triggers of Asthma and COPD - Infections A1 - Message SD A1 - Johnston SL ED - Barnes PJ; Drazen JM; Rennard S; Thomson NC T2 - Asthma and COPD: basic mechanisms and clinical management Y1 - 2002/// PB - Academic Press CY - London SN - 0-1207-9028-9 SP - 407 EP - 420 N2 - - ER - TY - CHAP T1 - Pulmonary vascular dysfunction in sepsis A1 - Finney SJ A1 - Wort SJ A1 - Evans TW ED - Fink M, Evans T T2 - Mechanisms of organ dysfunction in critical illness Y1 - 2002/01// PB - Springer Verlag CY - Berlin SP - 205 EP - 221 N2 - - ER - TY - CHAP T1 - Valvular heart disease A1 - Mohiaddin RH A1 - Kilner PJ T2 - Cardiovascular magnetic resonance Y1 - 2002/// SN - 0-4430-7519-0 SP - 387 EP - 404 N2 - - ER - TY - CHAP T1 - Asthma in infants and children A1 - Bush A T2 - Clinicians' Guide to Asthma Y1 - 2002/// SN - 0-3407-6287-X SP - 115 EP - 133 N2 - - ER - TY - CHAP T1 - Immunopathogenesis of viral infections in children A1 - Openshaw PJM A1 - Matthews S A1 - Pala P A1 - Hussell T A1 - Walzi G T2 - Textbook of respiratory cell and molecular biology Y1 - 2002/// SN - 9-0582-3178-X SP - 283 EP - 298 N2 - - ER - TY - CHAP T1 - Assessment of cardiac function A1 - Bellenger NG A1 - Pennell DJ T2 - Cardiovascular Magnetic Resonance Y1 - 2002/// SN - 0-4430-7519-0 SP - 99 EP - 111 N2 - - ER - TY - CHAP T1 - The use of navigator echoes in cardiovascular magnetic resonance and factors affecting their implimentation A1 - Firmin DN A1 - Keegan J T2 - Cardiovascular magnetic resonance Y1 - 2002/// SN - 0-4430-7519-0 SP - 186 EP - 195 N2 - - ER - TY - CHAP T1 - Smoking and the Lung. A1 - Tetley TD ED - Caan W, De Belleroche J. T2 - Drink, Drugs and Dependency. From science to clinical practice. Y1 - 2002/// PB - Gordon & Breach CY - New York; London SN - 0415-27891-0 SP - 93 EP - 106 N2 - - ER - TY - CHAP T1 - Future therapies for asthma A1 - Barnes PJ T2 - Biotherapeutic approaches to asthma Y1 - 2002/// SN - 0-8247-0785-0 SP - 352 EP - 382 N2 - - ER - TY - CHAP T1 - Cell adhesion molecules and leukocyte trafficking in sepsis A1 - Finney SJ A1 - Evans TW A1 - Burke-Gaffney A ED - Vincent JL T2 - Yearbook of Intensive Care and Emergency Medicine Y1 - 2002/// PB - Springer Verlag CY - Berlin SP - 23 EP - 38 N2 - - ER - TY - CHAP T1 - The use of navigator echoes in cardiovascular magnetic resonance and factors affecting their implimentation A1 - Firmin DN A1 - Keegan J T2 - Cardiovascular magnetic resonance Y1 - 2002/// SN - 0-4430-7519-0 SP - 186 EP - 195 N2 - - ER - TY - CHAP T1 - Hormone replacement therapy and carbohydrate metabolism A1 - Stevenson JC T2 - Hormone replacement therapy and the menopause Y1 - 2002/// SN - 1-8531-7691-5 SP - 101 EP - 113 N2 - - ER - TY - CHAP T1 - Biology of asthma A1 - Barnes PJ T2 - Disease markers in exhaled breath: Basic mechanisms and clinical applications Y1 - 2002/// SN - 1-5860-3273-9 SP - 133 EP - 142 N2 - - ER - TY - CHAP T1 - Pulmonary physiology A1 - Pride NB ED - PJ Barnes; JM Drazen; S Rennard; NC Thomson T2 - Asthma and COPD: basic mechanisms and clinical management Y1 - 2002/// PB - Academic Press CY - London SN - 0-1207-9028-9 SP - 43 EP - 56 N2 - - ER - TY - CHAP T1 - New treatments for COPD A1 - Barnes PJ T2 - Clinical management of chronic obstructive pulmonary disease Y1 - 2002/// SN - 0-8247-0610-2 SP - 943 EP - 963 N2 - - ER - TY - CHAP T1 - Blood flow velocity assessment A1 - Firmin DN T2 - Cardiovascular magnetic resonance Y1 - 2002/// SN - 0-4430-7519-0 SP - 53 EP - 62 N2 - - ER - TY - CHAP T1 - Mediator antagonists A1 - Chung KF A1 - Barnes PJ T2 - Asthma and COPD: basic mechanical and clinical management Y1 - 2002/// SN - 0-1207-9028-9 SP - 565 EP - 571 N2 - - ER - TY - CHAP T1 - Cystic fibrosis in lung transplantation A1 - Hodson ME ED - Banner NR; Polak J; Yacoub M Y1 - 2002/// PB - Cambridge University Press N2 - - ER - TY - CHAP T1 - What are the mechanisms of corticosteroids resistance in asthma? A1 - Barnes PJ T2 - Asthma: Critical debates Y1 - 2002/// SN - 0-6320-5721-1 SP - 241 EP - 254 N2 - - ER - TY - CHAP T1 - Regulation and organization of human troponin genes A1 - Barton PJR A1 - Dellow KA A1 - Bhavsar PK A1 - Cullen ME A1 - Mullen AJ A1 - Brand NJ T2 - Myofibrillogenesis Y1 - 2002/// PB - Birkhauser CY - Boston SN - 0-8176-4226-9 SP - 129 EP - 141 N2 - - ER - TY - CHAP T1 - Allergen-specific immunotherapy A1 - Kay AB A1 - Larche M T2 - Biotherapeutic approaches to asthma Y1 - 2002/// SN - 0-8247-0785-0 SP - 305 EP - 326 N2 - - ER - TY - CHAP T1 - Molecular mechanisms of steroid actions A1 - Adcock IM A1 - Ito K T2 - Disease markers in exhaled breath: basic mechanisms and clinical applications Y1 - 2002/// SN - 1-5860-3273-9 SP - 151 EP - 158 N2 - - ER - TY - CHAP T1 - Genetics and pathogenesis of cystic fibrosis A1 - Griesenbach U A1 - Geddes DM A1 - Alton EW T2 - Textbook of respiratory cell and molecular biology Y1 - 2002/// SN - 9-0582 3178-X SP - 403 EP - 418 N2 - - ER - TY - CHAP T1 - Scientific evidence and expert opinion for the selection and use of long-acting ß2 agonists: central considerations of safety and effectiveness A1 - Hansel TT A1 - Barnes PJ T2 - The Effective Management of Asthma Y1 - 2002/// SN - 1-9030-4426-X SP - 61 EP - 73 N2 - - ER - TY - CHAP T1 - Pathophysiology of asthma A1 - Barnes PJ A1 - Drazen JM T2 - Asthma and COPD: basic mechanical and clinical management Y1 - 2002/// SN - 0-1207-9028-9 SP - 343 EP - 359 N2 - - ER - TY - CHAP T1 - Blood flow velocity assessment A1 - Firmin DN T2 - Cardiovascular magnetic resonance Y1 - 2002/// SN - 0-4430-7519-0 SP - 53 EP - 62 N2 - - ER - TY - CHAP T1 - Practical application of secondary prevention for exertional angina A1 - Wood DA T2 - Effective secondary prevention and cardiac rehabilitation Y1 - 2002/// SN - 1-9030-4422-7 SP - 81 EP - 93 N2 - - ER - TY - CHAP T1 - NF-B function in inflammation, cellular stress and disease A1 - Chapman NR A1 - Rocha S A1 - Adcock IM A1 - Perkins ND T2 - Sensing, signaling and cell adaptation Y1 - 2002/// SN - 0-4445-1147-4 SP - 61 EP - 73 N2 - - ER - TY - CHAP T1 - Asthma A1 - Barnes PJ T2 - Pulmonary biology in health and disease Y1 - 2002/// SN - 0-3879-5215-2 SP - 364 EP - 380 N2 - - ER - TY - CHAP T1 - Theophylline A1 - Barnes PJ T2 - Asthma and COPD: basic mechanisms and clinical management Y1 - 2002/// SN - 0-1207-9028-9 SP - 535 EP - 545 N2 - - ER - TY - CHAP T1 - Chemokines A1 - Pease, J. E. A1 - Williams, T.J. ED - Barnes, P.J. et al T2 - Asthma and COPD Y1 - 2002/// VL - First PB - Academic Press SN - 0-12-079028-9 N2 - - ER - TY - CHAP T1 - Androgens and arterial disease A1 - Webb CM A1 - Collins P T2 - Textbooks of men's health Y1 - 2002/// SN - 1-8421-4011-6 SP - 360 EP - 364 N2 - - ER - TY - CHAP T1 - Pulmonary vascular diseases A1 - Bush A ED - Anderson RH, Baker EJ, Macartney F, Rigby ML, Shinebourne EA, Tynan M T2 - Paediatric Cardiology 2nd Edition Y1 - 2002/// PB - Churchill Livingstone SN - 0-4430-7990-0 SP - 567 EP - 592 N2 - - ER - TY - CHAP T1 - Should asthma be managed by the patient or doctor; is education important? A1 - Partridge MR ED - Holgate ST and Johnston L T2 - Asthma: critical debates Y1 - 2002/// PB - Blackwell Science CY - London SN - 0-6320-5721-1 SP - 355 EP - 365 N2 - - ER - TY - CHAP T1 - NCX overexpression in cardiac myocytes A1 - Terracciano CMN ED - J. Lytton; P. Schnetkamp, L. Hryshko, M. Blaunstein T2 - Cellular and molecular physiology of Sodium - Calcium exchange Y1 - 2002/// PB - New York Academy of Science CY - New York SP - 520 EP - 527 N2 - - ER - TY - CHAP T1 - Assessment of the biophysical mechanical properties of the arterial wall A1 - Mohiaddin RH T2 - Cardiovascular magnetic resonance Y1 - 2002/// SN - 0-4430-7519-0 SP - 272 EP - 279 N2 - - ER - TY - CHAP T1 - Imaging A1 - Desai SR A1 - Hansell DM T2 - Asthma and COPD: basic mechanisms and clinical management Y1 - 2002/// SN - 0-1207-9028-9 SP - 465 EP - 480 N2 - - ER - TY - CHAP T1 - Coronary artery and sinus velocity and flow A1 - Keegan J A1 - Pennell DJ T2 - Cardiovascular Magnetic Resonance Y1 - 2002/// SN - 0-4430-7519-0 SP - 233 EP - 249 N2 - - ER - TY - CHAP T1 - Autonomic control of the airways A1 - Barnes PJ T2 - Handbook of the autonomic nervous system in health and disease Y1 - 2002/// SN - 0-8247-0842-3 SP - 439 EP - 462 N2 - - ER - TY - CHAP T1 - Vascular Tone A1 - Hughes AD ED - Hunt BJ, Poston L, Schachter M, Halliday AW. T2 - An Introduction to Vascular Biology: From Basic Science to Clinical Practice Y1 - 2002/// PB - Cambridge University Press SN - 0-521-79652-0 SP - 3 EP - 32 N2 - - ER - TY - CHAP T1 - Education and self management A1 - Partridge MR T2 - Asthma and COPD: basic mechanisms and clinical management Y1 - 2002/// SN - 0-1207-9028-9 SP - 737 EP - 742 N2 - - ER - TY - CHAP T1 - A lifecourse approach to Diabetes A1 - Colhoun HM A1 - Chaturvedi N T2 - A lifecourse approach to women's health Y1 - 2002/// SN - 0-1926-3289-2 SP - 121 EP - 133 N2 - - ER - TY - CHAP T1 - Future therapies A1 - Barnes PJ T2 - Asthma and COPD: basic mechanisms and clinical management Y1 - 2002/// SN - 0-1207-9028-9 SP - 641 EP - 656 N2 - - ER - TY - CHAP T1 - Scientific evidence and expert opinion for the selection and use of long-acting ß2 agonists: central considerations of safety and effectiveness A1 - Hansel TT A1 - Barnes PJ T2 - The Effective Management of Asthma Y1 - 2002/// SN - 1-9030-4426-X SP - 61 EP - 73 N2 - - ER - TY - CHAP T1 - Other mediators of airway disease A1 - Barnes PJ T2 - Asthma and COPD: basic mechanisms and clinical management Y1 - 2002/// SN - 0-1207-9028-9 SP - 291 EP - 305 N2 - - ER - TY - CHAP T1 - Education and self management A1 - Partridge MR ED - Barnes PJ,Drazen J, Rennard S and Thomson N T2 - Asthma and COPD: basic mechanisms and clinical management Y1 - 2002/// PB - Academic Press CY - London SN - 0-1207-9028-9 SP - 737 EP - 742 N2 - - ER - TY - CHAP T1 - Chronic cough and/or wheezing in infants and children less than 5 years old: diagnostic approaches A1 - Bush A ED - Naspitz CK, Szefler SJ, Tinkelman DG, Warner JO T2 - Textbook of Paediatric Asthma Y1 - 2001/// PB - Martin Dunitz SN - 1-8531-7789-X SP - 99 EP - 120 N2 - - ER - TY - CHAP T1 - A realistic and efficient model of excitation propagation in the human atria A1 - Zemlin CW A1 - Herzel H A1 - Ho SY A1 - Panfilov A Y1 - 2001/// SN - 0-8799-3492-1 SP - 29 EP - 34 N2 - - ER - TY - CHAP T1 - Caldesmon A1 - El Mezgueldi M A1 - Marston SB Y1 - 2001/// SN - 0-4713-7494-6 SP - 428 EP - 430 N2 - - ER - TY - CHAP T1 - Mucus regulation A1 - Rogers DF A1 - Barnes PJ Y1 - 2001/// SN - 3-8055-6862-2 SP - 160 EP - 164 N2 - - ER - TY - CHAP T1 - Respiratory disease A1 - Bush A ED - Stroobant J, Field D T2 - Handbook of Paediatric Investigations Y1 - 2001/// PB - Churchill Livingstone SP - 260 EP - 309 N2 - - ER - TY - CHAP T1 - Rates of asthma exacerbations during viral respiratory infection A1 - Corne JM A1 - Johnston SL A1 - Beasley R Y1 - 2001/// SN - 0-8247-7710-7 N2 - - ER - TY - CHAP T1 - Altitude and expedition medicine A1 - Murdoch DR A1 - Pollard AJ A1 - Gibbs JS Y1 - 2001/// SN - 0-4714-9079-2 SP - 247 EP - 260 N2 - - ER - TY - CHAP T1 - The pathogenesis and treatment of asthma as an inflammatory disease A1 - Barnes PJ Y1 - 2001/// SN - 0-3064-6438-1 SP - 221 EP - 236 N2 - - ER - TY - CHAP T1 - Morphologic aspects A1 - Ho SY Y1 - 2001/// SN - 0-3407-6207-1 SP - 3 EP - 36 N2 - - ER - TY - CHAP T1 - La union auriculo-ventricular en la malformacion de Ebstein de la valvula tricuspide: relevancia durante la ablacion con cateter y radiofrecuencia. A1 - Cabrera JA A1 - Farre J A1 - Sanchez-Quintana D A1 - Rubio JM A1 - Ho SY A1 - Velasco D A1 - Cabestrero F A1 - Berreuzo A A1 - Anderson RH ED - : Merino JL T2 - Problems y Desafios en Arritmias y electrophisiologia Cardiaca. Y1 - 2001/// PB - St Jude CY - Madrid SP - 201 EP - 218 N2 - - ER - TY - CHAP T1 - Cardiovascular disease A1 - Poole-Wilson PA Y1 - 2001/// SN - 1-8990-4091-9 SP - 22 EP - 31 N2 - - ER - TY - CHAP T1 - Dissociated steroids A1 - Brown TJ A1 - Belvisi MG A1 - Foster ML Y1 - 2001/// SN - 3-8055-6862-2 SP - 98 EP - 101 N2 - - ER - TY - CHAP T1 - Monitoring lung function A1 - Pride NB Y1 - 2001/// SN - 3-8055-6862-2 SP - 30 EP - 34 N2 - - ER - TY - CHAP T1 - Angiotensin-converting enzyme (ACE) inhibitors, angiotensin-II receptor blockers (ARBs), and aldosterone antagonism A1 - Opie LH A1 - Yusuf S A1 - Poole-Wilson PA A1 - Pfeffer M Y1 - 2001/// M2 - 5th SN - 0-7216-8757-1 SP - 107 EP - 153 N2 - - ER - TY - CHAP T1 - Monitoring lung function A1 - Pride NB ED - Hansel TT and Barnes PJ T2 - New Drugs for Asthma, Allergy and COPD Y1 - 2001/// PB - Karger CY - Basel SN - 3-8055-6862-2 SP - 30 EP - 34 N2 - - ER - TY - CHAP T1 - Eosinophils A1 - Robinson DS A1 - Wardlaw AJ A1 - Kay AB Y1 - 2001/// M2 - 3 SN - 0-8247-0540-8 SP - 43 EP - 75 N2 - - ER - TY - CHAP T1 - Diuretics A1 - Opie LH A1 - Kaplan NM A1 - Poole-Wilson PA Y1 - 2001/// M2 - 5th SN - 0-7216-8757-1 SP - 84 EP - 106 N2 - - ER - TY - CHAP T1 - What is the role of echocardiography in acute coronary syndromes? A1 - Nihoyannopoulos P ED - de Bono D and Sobel BE T2 - Acute Coronary Syndromes Y1 - 2001/// PB - Blackwell Science Ltd SP - 188 EP - 200 N2 - - ER - TY - CHAP T1 - Gene regulation of muscarinic receptor subtypes A1 - Barnes PJ Y1 - 2001/// SN - 3-7643-5988-9 SP - 159 EP - 174 N2 - - ER - TY - CHAP T1 - Evidence for upper respiratory tract viruses as precipitants for asthma exacerbations A1 - Corne JM A1 - Johnston SL A1 - Beasley R ED - Skoner T2 - Asthma and Respiratory Infections Y1 - 2001/// PB - Marcel Dekker, Inc CY - New York SP - 45 EP - 62 N2 - - ER - TY - CHAP T1 - Use of exhaled nitric oxide as readout for inhaled corticosteroids efficacy A1 - Kharitonov SA A1 - Barnes PJ Y1 - 2001/// SN - 0-89603-923-4 SP - 441 EP - 463 N2 - - ER - TY - CHAP T1 - Mortality in heart failure; selected aspects of pathophysiology and the implications of recent trials A1 - Poole-Wilson PA Y1 - 2001/// SN - 0-6202-7326-7 SP - 69 EP - 86 N2 - - ER - TY - CHAP T1 - Eosinophils A1 - Robinson DS A1 - Wardlaw AJ A1 - Kay AB Y1 - 2001/// M2 - 3 SN - 0-8247-0540-8 SP - 43 EP - 75 N2 - - ER - TY - CHAP T1 - Airway Epithelial Cells (Primaries vs Cell lines) A1 - Donnelly LE Y1 - 2001/// M2 - 10 SN - 0-89603-923-4 SP - 127 EP - 136 N2 - - ER - TY - CHAP T1 - Specific and non-specific immunotherapy for asthma and allergic diseases A1 - Larche M A1 - Kay AB Y1 - 2001/// M2 - 2nd (26) SN - 0-6320-4359-8 SP - 352 EP - 370 N2 - - ER - TY - CHAP T1 - Answers to questions 63,64,66,67,68,69,70, 71,72 A1 - Hardman S A1 - Cowie MR Y1 - 2001/// SN - 0-7279-1489-8 SP - 133 EP - 152 N2 - - ER - TY - CHAP T1 - Mucus regulation A1 - Rogers DF ED - TT Hansel PJ Barnes T2 - New Drugs for Asthma, Allergy and COPD Y1 - 2001/// SN - 3-8055-6862-2 SP - 160 EP - 164 N2 - - ER - TY - CHAP T1 - Measurement of granulocyte pharmacodynamics in whole blood by flow cytometry A1 - Bryan SA A1 - Leckie MJ A1 - Jenkins G A1 - Barnes PJ A1 - Williams TJ A1 - Sabroe I A1 - Hansel TT Y1 - 2001/// SN - 0-8960-3923-4 N2 - - ER - TY - CHAP T1 - Monitoring lung function A1 - Pride NB Y1 - 2001/// SN - 3-8055-6862-2 SP - 30 EP - 34 N2 - - ER - TY - CHAP T1 - Cystic fibrosis: cause, course and treatment A1 - Bush A ED - Bluebond-Langner M, Lask B, Angst DB T2 - Pschological Aspects of Cystic Fibrosis Y1 - 2001/// PB - Arnold SN - 0-3407-5891-0 SP - 1 EP - 25 N2 - - ER - TY - CHAP T1 - What are hibernating and stunned myocardium? What echocardiographic techniques are useful for detecting them? How do these methods compare with others available? A1 - Nihoyannopoulos P ED - Holdright D, Montomery H T2 - 100 Questions in cardiology Y1 - 2001/// PB - BMJ Books SP - 33 N2 - - ER - TY - CHAP T1 - Analysing MHC class II processing and presentation: from processed avidin to H2-0 modulation and T cell receptor signals A1 - Altmann D M A1 - Perraudeau M A1 - Douek D C A1 - Boyton R J ED - Steinman L T2 - Autoimmunity and Emerging Diseases Y1 - 2001/// PB - CSED SP - 1 EP - 11 N2 - - ER - TY - CHAP T1 - Use of exhaled nitric oxide as readout for inhaled corticosteroids efficacy A1 - Kharitonov SA A1 - Barnes PJ Y1 - 2001/// SN - 0-89603-923-4 SP - 441 EP - 463 N2 - - ER - TY - CHAP T1 - Measurement of exhaled nitric oxide and carbon monoxide A1 - Kharitonov SA A1 - Barnes PJ Y1 - 2001/// SN - 3-8055-6862-2 SP - 44 EP - 47 N2 - - ER - TY - CHAP T1 - A realistic model of excitation propagation in the human atria. A1 - Zemlin ChW A1 - Herzel H A1 - Ho SY A1 - Panfilov A ED - Virag N, Blanc O, Kappenberger L T2 - Computer simulation and experimental assessment of cardiac electrophysiology. Y1 - 2001/// PB - Futura Publishing Co Inc CY - Armonk, NY SN - 0-8799-3492-1 SP - 29 EP - 34 N2 - - ER - TY - CHAP T1 - Nuclear cardiology A1 - Underwood SR A1 - Anagnostopoulos C Y1 - 2001/// M2 - 4th SN - 0-4430-6432-6 SP - 721 EP - 740 N2 - - ER - TY - CHAP T1 - Bone metabolism A1 - Colston KW A1 - Stevenson JC Y1 - 2001/// M2 - 2nd SN - 0-3337-2306-6 SP - 529 EP - 540 N2 - - ER - TY - CHAP T1 - Eosinophils and their disorders A1 - Wardlaw AJ A1 - Kay AB Y1 - 2001/// M2 - 6th (68) SN - 0-0707-0397-3 SP - 785 EP - 799 N2 - - ER - TY - CHAP T1 - La union auriculo-ventricular en la malformacion de Ebstein de la valvula tricuspide: relevancia durante la ablacion con cateter y radiofrecuencia A1 - Cabrera JA A1 - Farre J A1 - Sanchez-Quintana D A1 - Rubio JM A1 - Ho SY A1 - Velasco D A1 - Cabestrero F A1 - Berreuzo A A1 - Anderson RH Y1 - 2001/// SP - 201 EP - 218 N2 - - ER - TY - CHAP T1 - Inflammatory mediators and neural mechanisms in severe asthma A1 - Barnes PJ Y1 - 2001/// M2 - 2nd SN - 0-8247-0552-1 SP - 67 EP - 87 N2 - - ER - TY - CHAP T1 - In vivo models of airway goblet cell hyperplasia and mucin gene expression A1 - Smith AK A1 - Rogers DF ED - M Salathe T2 - Cilia and Mucus: From Development to Respiratory Defence Y1 - 2001/// SN - 0-8247-0441-X SP - 239 EP - 251 N2 - - ER - TY - CHAP T1 - Propellants A1 - Partridge MR A1 - Woodcock ED - Bisgaard H, O'Callaghan C and Smaldone GC T2 - Lung Biology in Health and Disease Series No 162 Y1 - 2001/// PB - Marcel Dekker CY - New York SN - 0-8247-0541-6 SP - 371 EP - 388 N2 - - ER - TY - CHAP T1 - Dissociated steroids A1 - Brown TJ A1 - Belvisi MG A1 - Foster ML Y1 - 2001/// SN - 3-8055-6862-2 SP - 98 EP - 101 N2 - - UR - NULL ER - TY - CHAP T1 - Muscarinic control of airway mucus secretion A1 - Rogers DF ED - J Zaagsma et al T2 - Muscarinic Receptors in Airway Diseases Y1 - 2001/// SN - 3-7643-5988-9 SP - 175 EP - 201 N2 - - ER - TY - CHAP T1 - Measurement of exhaled nitric oxide and carbon monoxide A1 - Kharitonov SA A1 - Barnes PJ Y1 - 2001/// SN - 3-8055-6862-2 SP - 44 EP - 47 N2 - - ER - TY - CHAP T1 - Specific and non-specific immunotherapy for asthma and allergic diseases A1 - Larche M A1 - Kay AB Y1 - 2001/// M2 - 2nd (26) SN - 0-6320-4359-8 SP - 352 EP - 370 N2 - - ER - TY - CHAP T1 - Advances in the diagnosis of respiratory virus infectons A1 - Chauhan AJ A1 - Johnston SL ED - Skoner DP T2 - Asthma and Respiratory Infections Y1 - 2001/// PB - Marcek Dekker SN - 0-8247-7710-7 SP - 221 EP - 243 N2 - - ER - TY - CHAP T1 - Giving the diagnosis A1 - Bush A ED - Bluebond-Langner M, Lask B, Angst DB T2 - Pschological Aspects of Cystic Fibrosis Y1 - 2001/// PB - Arnold SN - 0-3407-5891-0 SP - 97 EP - 109 N2 - - ER - TY - CHAP T1 - Measurement of airway mucin gene expression A1 - Pritchard K A1 - Smith AK A1 - Rogers DF ED - DF Rogers LE Donnelly T2 - Human Airway Inflammation: Sampling Techniques and Analytical Protocols Y1 - 2001/// SN - 0-89603-923-4 SP - 285 EP - 294 N2 - - ER - TY - CHAP T1 - The technique of in situ hybridization A1 - Ying S A1 - Kay AB Y1 - 2001/// SN - 0-89603-923-4 SP - 263 EP - 283 N2 - - ER - TY - CHAP T1 - Regulation and organization of human troponin genes A1 - Barton PJR A1 - Dellow KA A1 - Bhavsar PK A1 - Cullen ME A1 - Mullen AJ A1 - Brand NJ Y1 - 2001/// SN - 0-8176-4226-9 SP - 129 EP - 141 N2 - - ER - TY - CHAP T1 - Measurement of granulocyte pharmacodynamics in whole blood by flow cytometry A1 - Bryan SA A1 - Leckie MJ A1 - Jenkins G A1 - Barnes PJ A1 - Williams TJ A1 - Sabroe I A1 - Hansel TT Y1 - 2001/// SN - 0-8960-3923-4 N2 - - ER - TY - CHAP T1 - Measurement of exhaled hydrocarbons A1 - Kharitonov SA Y1 - 2001/// SN - 0-89603-923-4 SP - 99 EP - 108 N2 - - ER - TY - CHAP T1 - Isolation and Culture of Human Alveolar Type II Pneumocytes A1 - Witherden IR A1 - Tetley TD ED - Rogers DF, Donnelly LE. T2 - Human Airway Inflammation: Sampling Techniques and Analytical Protocols Y1 - 2001/// PB - Humana Press CY - New Jersey SN - 0-89603-923-4 SP - 137 EP - 146 N2 - - ER - TY - CHAP T1 - Dissociated steroids A1 - Brown TJ A1 - Belvisi MG A1 - Foster ML Y1 - 2001/// SN - 3-8055-6862-2 SP - 98 EP - 101 N2 - - ER - TY - CHAP T1 - Cardiovascular magnetic resonance in the diagnosis and management of angina A1 - Bellenger NG A1 - Pennell DJ Y1 - 2001/// SN - 0-7234-3255-4 SP - 22 EP - 26 N2 - - ER - TY - CHAP T1 - Measurement of exhaled nitric oxide and carbon monoxide A1 - Kharitonov SA A1 - Barnes PJ Y1 - 2001/// SN - 3-8055-6862-2 SP - 44 EP - 47 N2 - - ER - TY - CHAP T1 - Pathophysiology of heart failiure A1 - Purcell IF A1 - Poole-Wilson PA Y1 - 2001/// SN - 0-7216-8144-1 SP - 345 EP - 364 N2 - - ER - TY - CHAP T1 - Chemokines and Eosinophils A1 - Hartnell, A. A1 - Pease, J. E. A1 - Conroy, D.M., A1 - Williams, T.J. ED - Holgate S & Busse W. T2 - Asthma & Rhinitis Y1 - 2000/// VL - Second Edition SN - 0-632-04175-7 N2 - - ER - TY - CHAP T1 - Neutrophil- and macrophage-derived proteases in chronic obstructive pulmonary disease and acute respiratory distress syndrome. A1 - Tetley TD ED - Bellingan G, Laurent GJ T2 - Acute Lung Injury: From Inflammation to Repair Y1 - 2000/// PB - IOS Press CY - Amsterdam SN - 90-5199-503-2 SP - 129 EP - 142 N2 - - ER - TY - CHAP T1 - Common colds and respiratory viruses A1 - Bates A1 - Johnston SL ED - Busse WW; Katarelis CH T2 - Asthma and rhinitis Y1 - 2000/// PB - Blackwell Science CY - London SP - 1481 EP - 1492 N2 - - ER - TY - CHAP T1 - Mechanisms of respiratory syncytial virus induced asthma A1 - Johnston SL ED - Rimmer JS; Katarelis CH T2 - Proceedings XVII International Congress of Allergology and Clinical Immunology Y1 - 2000/// PB - Hogrefe & Huber Pubs CY - Seattle SP - 101 EP - 102 N2 - - ER - TY - CHAP T1 - Aortic Diseases A1 - Mohiaddin RH, A1 - Kilner PJ, A1 - Pennell DJ. ED - Pohost GM, O’Rourke RA, Shah PM, Berman DS. T2 - Imaging in cardiovascular disease Y1 - 2000/// PB - Lippincott Williams and Wilkins CY - Philadeplphia SP - 821 EP - 842 N2 - - ER - TY - CHAP T1 - Contrast Echocardiography A1 - Nihoyannopoulos P ED - Dawson P, Cosgrove D, Grainger RG T2 - Textbook of Contrast Media Y1 - 2000/// PB - ISIS Medical Media SP - 543 EP - 548 N2 - - ER - TY - CHAP T1 - Freeze-fracture cytochemistry: the fracture-label technique. A1 - Severs, N.J. ED - Rickwood, D. and Harris, J.R. T2 - Multimedia Methods in Cell Biology. Y1 - 1999/// PB - CRC Press CY - Boca Raton N2 - - ER - TY - CHAP T1 - The role of echocardiography in diagnosis and management of cardiac syndrome X A1 - Nihoyannopoulos P ED - Kaski JC T2 - Chest pain with normal coronary angiograms. Pathogenesis, diagnosis and management Y1 - 1999/// PB - Kluer SP - 171 EP - 180 N2 - - ER - TY - CHAP T1 - The acute exacerbation of asthma:pathogenesis A1 - Papadopoulos NG A1 - Johnston SL ED - Holgate ST: Boushey HA; Fabbri LM T2 - Difficult asthma Y1 - 1999/// PB - Martin Dunitz CY - London SP - 183 EP - 204 N2 - - ER - TY - CHAP T1 - Rhinoviruses A1 - Papadopoulos NG A1 - Johnston SL ED - Zuckerman; Banatvala; Pattison T2 - Principles and Practice of Clinical Virology Fourth Edition Y1 - 1999/// PB - John Wiley & Son CY - UK SP - 329 EP - 343 N2 - - ER - TY - CHAP T1 - Freeze-fracture replication using simple inexpensive equipment, the Bullivant method. A1 - Severs, N.J. ED - Rickwood, D. and Harris, J.R T2 - Multimedia Methods in Cell Biology Y1 - 1999/// PB - CRC Press CY - Boca Raton N2 - - ER - TY - CHAP T1 - Freeze-fracture and freeze-etching using a purpose-built machine, the Balzers (Bal-Tec) BAF 400 T system. A1 - Severs, N.J ED - Rickwood, D. and Harris, J.R T2 - Multimedia Methods in Cell Biology Y1 - 1999/// PB - CRC Press CY - Boca Raton N2 - - ER - TY - CHAP T1 - Triggers of asthma: viruses A1 - Busse WW A1 - Johnston SL ED - Djukanovic R; Holgate ST T2 - An atlas of asthma Y1 - 1999/// PB - Parthenon Publishing Group CY - London SP - 63 EP - 68 N2 - - ER - TY - CHAP T1 - Chlamydia pneumoniae infections in children A1 - Biscione GL A1 - Johnston SL ED - Allegra L; Blasi F T2 - Chlamydia pneumoniae the lung and heart Y1 - 1999/// PB - Springer-Verlag Italia CY - Milano SP - 197 EP - 203 N2 - - ER - TY - CHAP T1 - Simultaneous localization of connexins 40, 37 and 43 in pulmonary artery endothelial gap junctions. A1 - Ko, Y.-S A1 - Yeh, H.-I. A1 - Rothery, S. A1 - Dupont, E. A1 - Severs, N.J. ED - Werner, R. T2 - Gap Junctions. Proceedings of the 8th International Gap junction Conference, Key Largo, Florida. Y1 - 1998/// PB - IOS publishers CY - Florida SP - 183 EP - 187 N2 - - ER - TY - CHAP T1 - Rapid freezing of biological specimens for freeze fracture and deep etching. A1 - Severs, N.J A1 - Shotton, D.M ED - Celis, J.E T2 - Cell Biology: A Laboratory Handbook Y1 - 1998/// VL - 2nd M2 - 3 PB - Academic Press CY - San Diego SN - 0-12-164714-5 SP - 299 EP - 309 N2 - - ER - TY - CHAP T1 - T cell antigen receptor signalling events associated with differential cytokine responses in autoimmunity A1 - Boyton R J A1 - Altmann D M T2 - Proceedings of the 10th International Congress of Immunology (New Delhi, India, 1-7 November 1998) Y1 - 1998/// PB - Monduzzi Editore - International Proceedings Division N2 - - ER - TY - CHAP T1 - Imaging of Adults with Congenital Heart Disease A1 - Philip J Kilner ED - Lima J T2 - Diagnostic Imaging in Clinical Cardiology Y1 - 1998/// PB - Martin Dunitz CY - London UK SP - 211 EP - 233 N2 - - ER - TY - CHAP T1 - Gap junctions and coronary heart disease. A1 - Severs, N.J. ED - De Mello, W.C. and Janse, M.J T2 - Heart Cell Communication in Health and Disease. Y1 - 1998/// PB - Kluwer CY - Boston SN - 0-7923-8052-5 SP - 175 EP - 194 N2 - - ER - TY - CHAP T1 - Isolation and culture of adult cardiac myocytes. A1 - Powell, T A1 - Noma, A. A1 - Severs, N.J. ED - Celis, J.E T2 - Cell Biology: A Laboratory Handbook. Y1 - 1998/// VL - 2nd M2 - 1 PB - Academic Press CY - London SP - 125 EP - 132 N2 - - ER - TY - CHAP T1 - Ryanodine receptor ion conduction and selectivity A1 - A.J. Williams ED - R. Sitsapesan and A.J. Williams T2 - The structure and function of ryanodine receptors Y1 - 1998/// PB - Imperial College Press CY - London SN - 1-86094-145-1 SP - 75 EP - 94 N2 - - ER - TY - CHAP T1 - Allergy A1 - Frew AJ A1 - Bradding P A1 - Johnston SL A1 - Lackie P A1 - Semper A A1 - Shute A A1 - Walls AF A1 - Holgate ST ED - Tomlinson, Heagerty, Weetman T2 - Mechanisms of Disease Y1 - 1997/// PB - Cambridge University Press CY - UK SP - 129 EP - 159 N2 - - ER - TY - CHAP T1 - Functional microanatomy of the cardiac muscle cell and its gap junctions. A1 - Severs, N.J. ED - Motta, P.M T2 - Recent Advances in Microscopy of Cells, Tissues and Organs. Y1 - 1997/// PB - La Sapienza CY - Rome SN - 88-7287-130-1 SP - 281 EP - 290 N2 - - ER - TY - CHAP T1 - Cardiovascular manifestation in pregnancy and the approach to diagnosis of cardiac disorder A1 - Nihoyannopoulos P ED - Oakley CM T2 - Heart disease in pregnancy Y1 - 1997/// PB - BMJ publishers SP - 52 EP - 62 N2 - - ER - TY - CONF T1 - Modification of biological scaffolds with specific extracellular matrix proteins enhances collagen synthesis by mesenchymal stem cells A1 - Dreger, SA A1 - Chester, AH A1 - Bowles, CT A1 - Yacoub, MH A1 - Taylor, PM U1 - Conference of the Tissue-Engineering-and-Regenerative-Medicine-International-Society (TERMIS-EU) Y1 - 2007/07// Y2 - // VL - 13 SP - 1729 EP - 1729 N2 - - ER - TY - CONF T1 - Glycosaminoglycan synthesis by mesenchymal stem cells in response to stretch A1 - New, SEP A1 - Chester, AH A1 - Yacoub, MH A1 - Taylor, PM U1 - Conference of the Tissue-Engineering-and-Regenerative-Medicine-International-Society (TERMIS-EU) Y1 - 2007/07// Y2 - // VL - 13 SP - 1702 EP - 1702 N2 - - ER - TY - CONF T1 - Hydrodynamic evaluation of a bioreactor for tissueengineering heart valves A1 - Bowles, CT A1 - Van Loon, R A1 - Dreger, SA A1 - Biglino, G A1 - Chan, C A1 - Parker, KH A1 - Chester, AH A1 - Taylor, PM A1 - Yacoub, MH U1 - Conference of the Tissue-Engineering-and-Regenerative-Medicine-International-Society (TERMIS-EU) Y1 - 2007/07// Y2 - // VL - 13 SP - 1708 EP - 1708 N2 - - ER - TY - CONF T1 - Effect of alpha 2, alpha 5 and alpha nu beta 3 integrins on mesenchymal stem cell adhesion to extracellular matrix proteins A1 - Dreger, SA A1 - Taylor, PM A1 - Yacoub, MH A1 - Chester, AH U1 - Conference of the Tissue-Engineering-and-Regenerative-Medicine-International-Society (TERMIS-EU) Y1 - 2007/07// Y2 - // VL - 13 SP - 1677 EP - 1678 N2 - - ER - TY - CONF T1 - Health effects of nanomaterials A1 - Tetley, TD U1 - Cojnference on Bionanotechnology - From Self-Assembly to Cell Biology Y1 - 2007/06// Y2 - // VL - 35 SP - 527 EP - 531 N2 - - ER - TY - CONF T1 - Magnetic resonance of the heart A1 - Pennell, D U1 - 39th International Diagnostic Course Meeting Y1 - 2007/// Y2 - // SP - 149 EP - 153 N2 - - ER - TY - CONF T1 - Cardiac morphology and atrial fibrillation: basic mechanism or target to therapy? 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Y1 - 2004/// Y2 - 2004/// VL - 113 PB - Immunology N2 - - ER - TY - CONF T1 - The TEW method for crosstalk correction in simultneous 201Tl/99mTc myocardial perfusion SPECT maging A1 - van Aswegen A A1 - Loong CY A1 - Underwood SR U1 - British Nuclear Medicine Society AD - Brighton, UK Y1 - 2004/// Y2 - 2004/// VL - 25 PB - Nucl Med Commun SP - 422 N2 - - ER - TY - CONF T1 - Cardiac rehabilitation A1 - Cowie, MR U1 - Symposium on What About the Workers Y1 - 2004/// Y2 - // SP - 51 EP - 56 N2 - - ER - TY - CONF T1 - LV function parameters obtained from gated myocardial SPECT imaging: a comparison of two data processing systems A1 - Tout D A1 - Rogers A A1 - van Aswegen A A1 - Underwood SR U1 - British Nuclear Medicine Society AD - Brighton, UK Y1 - 2004/// Y2 - 2004/// VL - 25 PB - Nucl Med Commun SP - 423 N2 - - ER - TY - CONF T1 - FDG gamma camera PET in the detrection of viable myocardium in chronic ischaemic left ventricular dysfunction A1 - Loong CY A1 - Prvulovich EM A1 - Reyes E A1 - Smith R A1 - Wechalekar K A1 - van Aswegen A A1 - Anagnostopoulos C A1 - Ell PJ A1 - Underwood SR U1 - British Nuclear Medicine Society AD - Brighton, UK Y1 - 2003/// Y2 - 2003/// VL - 24 PB - Nucl Med Commun SP - 464 EP - 465 N2 - - ER - TY - CONF T1 - The morphology of the cardiac conduction system. . , A1 - Anderson RH U1 - Novartis Foundation Symposium 250 AD - London UK J1 - Development of the cardiac conduction system. Y1 - 2003/// Y2 - 2003/// PB - John Wiley & Son Ltd CY - Chichester UK SP - 6 EP - 17 N2 - - ER - TY - CONF T1 - Induction of antigen-specific T-cell regulation through peptide immunotherapy A1 - Alexander, C A1 - Forsyth, L A1 - Ying, S A1 - Verhoef, A A1 - Lamb, J A1 - Kay, AB A1 - Larche, M U1 - 27th Symposium of the Collegium-Internationale-Allergologicum Y1 - 2003/// Y2 - // SP - 320 EP - 323 N2 - - ER - TY - CONF T1 - Allergen immunotherapy: Immune deviation or anergy? A1 - Nouri-Aria, KT A1 - Wilson, DR A1 - Durham, SR U1 - 27th Symposium of the Collegium-Internationale-Allergologicum Y1 - 2003/// Y2 - // SP - 342 EP - 345 N2 - - ER - TY - CONF T1 - Tobacco chloroplasts as a platform for vaccine production. A1 - Maliga P A1 - Tregoning J A1 - Kuroda H A1 - Svab Z A1 - Lutz K A1 - Corneille S A1 - Nixon P A1 - Clare S A1 - Bowe F A1 - Fairweather N A1 - Dougan G U1 - Plant Biotechnology 2002 and Beyond AD - Orlando, Florida, USA Y1 - 2003/// Y2 - 2003/// PB - Kluwer Academic Publishers SP - 397 EP - 400 N2 - - ER - TY - CONF T1 - Clinical pathology of the cardiac conduction system. A1 - Ho SY U1 - Novartis Foundation Symposium 250 J1 - Development of the cardiac conduction system Y1 - 2003/// Y2 - 2003/// PB - John Wiley & Sons Ltd CY - Chichester UK SP - 210 EP - 220 N2 - - ER - TY - CONF T1 - Intra-ventricular blood flow simulation with patient specific geometry A1 - Long, Q A1 - Merrifield, R A1 - Xu, XY A1 - Kilner, PJ A1 - Firmin, DN A1 - Yang, GZ U1 - 4th International Conference on Information Technology Applications in Biomedicine (ITAB 2003) Y1 - 2003/// Y2 - // SP - 126 EP - 129 N2 - - ER - TY - CONF T1 - 3D ultrasound-based CFD for carotid flow prediction: a reproducibility study A1 - Glor, FP A1 - Ariff, B A1 - Augst, AD A1 - Barratt, DC A1 - Hughes, AD A1 - Thom, SAM A1 - Verdonck, P A1 - Xu, XY U1 - 2nd MIT Conference on Computational Fluid and Solid Mechanics Y1 - 2003/// Y2 - // SP - 1701 EP - 1704 N2 - - ER - TY - CONF T1 - Communicating junctions, connexins and the cardiomyocyte: From cell biology to cardiology A1 - Severs, NJ U1 - 17th World Heart Congress Y1 - 2003/// Y2 - // VL - 5 SP - 417 EP - 434 N2 - - ER - TY - CONF T1 - Ventilation-perfusion scintigraphy in the diagnosis of pulmonary embolism in the presence of metastatic lung disease A1 - Wechalekar K A1 - Reyes E A1 - Loong CY A1 - Bailey J A1 - Naidoo VV A1 - Anagnostopoulos C A1 - Underwood SR U1 - European Association of Nucelar Medicine AD - Amsterdam Y1 - 2003/// Y2 - 2003/// PB - Eur J Nucl Med N2 - - ER - TY - CONF T1 - Effect of anti-IL-5 (mezolizumab) on airway eosinophils in asthmatics A1 - Kay, AB A1 - Flood-Page, PT A1 - Menzies-Gow, AN A1 - Robinson, DS U1 - 27th Symposium of the Collegium-Internationale-Allergologicum Y1 - 2003/// Y2 - // SP - 298 EP - 301 N2 - - ER - TY - CONF T1 - The effect of attenuation correction on normal regional uptake in myocardial SPECT using different perfusion tracers A1 - Jogiya R A1 - van Aswegen A A1 - Loong CY A1 - Kundley K A1 - Underwood SR U1 - British Nucelar Medicine Society AD - Brighton, UK Y1 - 2003/// Y2 - 2003/// VL - 24 PB - Nucl Med Commun SP - 465 N2 - - ER - TY - CONF T1 - Cardiovascular disease at high altitude A1 - Gibbs JSR A1 - Galliford J U1 - 5th World Congress on Mountain Medicine AD - Barcelona, Spain Y1 - 2003/// Y2 - 2003/// PB - Universitat de Barcelona CY - Barcelona SP - 181 EP - 186 N2 - - ER - TY - CONF T1 - COPD alters the diaphragm motor area response to transcranial magnetic stimulation A1 - Hopkinson, NS A1 - Sharshar, T A1 - Ross, E A1 - Dayer, MJ A1 - Nickol, AH A1 - Moxham, J A1 - Polkey, MI U1 - Winter Meeting of the British-Thoracic-Society Y1 - 2002/12// Y2 - // VL - 57 SP - U50 EP - U50 N2 - - ER - TY - CONF T1 - Markers in exhaled air and condensate to monitor treatment in asthma A1 - Kharitonov, SA U1 - Conference of the NATO-Advanced-Study-Institute on Disease Markers in Exhaled Breath Y1 - 2002/// Y2 - // VL - 346 SP - 177 EP - 186 N2 - - ER - TY - CONF T1 - Early use of dornase alpha in cystic fibrosis - Con A1 - Bush, A U1 - 25th European Cystic Fibrosis Conference Y1 - 2002/// Y2 - // SP - 259 EP - 262 N2 - - ER - TY - CONF T1 - Disease markers in COPD: exhaled breath vs. exhaled condensate A1 - Kharitonov, SA U1 - Conference of the NATO-Advanced-Study-Institute on Disease Markers in Exhaled Breath Y1 - 2002/// Y2 - // VL - 346 SP - 218 EP - 222 N2 - - ER - TY - CONF T1 - Macrolides in cystic fibrosis A1 - Bush, A U1 - 25th European Cystic Fibrosis Conference Y1 - 2002/// Y2 - // SP - 255 EP - 258 N2 - - ER - TY - CONF T1 - The pathology of isolated left ventricular non-compaction (LVNC). A rare cause of heart failure A1 - Hughes, SE A1 - Elliott, P A1 - Kilner, P A1 - Ho, SY A1 - Morgan, D U1 - 8th World Congress on Heart Failure - Mechanisms and Management Y1 - 2002/// Y2 - // SP - 249 EP - 254 N2 - - ER - TY - CONF T1 - Molecular mechanisms of steroid actions A1 - Adcock, IM A1 - Ito, K U1 - Conference of the NATO-Advanced-Study-Institute on Disease Markers in Exhaled Breath Y1 - 2002/// Y2 - // VL - 346 SP - 151 EP - 158 N2 - - ER - TY - CONF T1 - Exhaled markers in cystic fibrosis A1 - Balint, B A1 - Kharitonov, SA A1 - Horvath, I A1 - Barnes, PJ U1 - Conference of the NATO-Advanced-Study-Institute on Disease Markers in Exhaled Breath Y1 - 2002/// Y2 - // VL - 346 SP - 234 EP - 241 N2 - - ER - TY - CONF T1 - NO is generated via NOS enzymes A1 - Kharitonov, SA U1 - Conference of the NATO-Advanced-Study-Institute on Disease Markers in Exhaled Breath Y1 - 2002/// Y2 - // VL - 346 SP - 57 EP - 61 N2 - - ER - TY - CONF T1 - Biology of asthma A1 - Barnes, PJ U1 - Conference of the NATO-Advanced-Study-Institute on Disease Markers in Exhaled Breath Y1 - 2002/// Y2 - // VL - 346 SP - 133 EP - 142 N2 - - ER - TY - CONF T1 - A novel mucosal vaccine based on tetanus toxin fragment C expressed in tobacco chloroplasts. A1 - Tregoning JS A1 - Nixon P A1 - Kuroda H A1 - Svab Z A1 - Clare S A1 - Bowe F A1 - Fairweather N A1 - Ytterberg J A1 - van Wijk K A1 - Dougan G A1 - Maliga P U1 - 11th International Congress of Mucosal Immunology AD - Orlando, Florida Y1 - 2002/// Y2 - 2002/// PB - Curette, Tigon N2 - - ER - TY - CONF T1 - Technical aspects of exhaled NO: Investigator point of view A1 - Kharitonov, SA U1 - Conference of the NATO-Advanced-Study-Institute on Disease Markers in Exhaled Breath Y1 - 2002/// Y2 - // VL - 346 SP - 62 EP - 63 N2 - - ER - TY - CONF T1 - Sex steroids and the cardiovascular system in vivo: actions in humans A1 - Collins, P U1 - Workshop on Hormone Replacement Therapy and Cardiovascular Disease Y1 - 2001/// Y2 - // SP - 107 EP - 115 N2 - - ER - TY - CONF T1 - Mechanisms of estrogen action on the cardiovascular system A1 - Stevenson, JC U1 - 3rd International Symposium on Hormonal Carcinogenesis Y1 - 2001/// Y2 - // SP - 365 EP - 371 N2 - - ER - TY - CONF T1 - A novel imaging strategy for structural segmentation of the left ventricle A1 - Merrifield, RD A1 - Keegan, J A1 - Firmin, DN A1 - Yang, GZ U1 - International Workshop on Medical Imaging and Augmented Reality (MIRA 2001) Y1 - 2001/// Y2 - // SP - 157 EP - 162 N2 - - ER - TY - CONF T1 - Virtual tagging for analysing cardiac deformation A1 - Masood, S A1 - Estcourt, GN A1 - Gatehouse, GN A1 - Firmin, DN A1 - Yang, GZ U1 - International Workshop on Medical Imaging and Augmented Reality (MIRA 2001) Y1 - 2001/// Y2 - // SP - 61 EP - 66 N2 - - ER - TY - CONF T1 - A method of vessel tracking for vessel diameter measurement on retinal images A1 - Gao, XH A1 - Bharath, A A1 - Stanton, A A1 - Hughes, A A1 - Chapman, N A1 - Thom, S U1 - International Conference on Image Processing (ICIP 2001) Y1 - 2001/// Y2 - // SP - 881 EP - 884 N2 - - ER - TY - CONF T1 - In vivo models of airway goblet cell hyperplasia and mucin gene expression A1 - Smith, AK A1 - Rogers, DF U1 - 2nd International Meeting on Cilia, Mucus, and Mucociliary Interactions Y1 - 2001/// Y2 - // SP - 239 EP - 251 N2 - - ER - TY - CONF T1 - End stage heart failure - options for medical treatment and beyond A1 - Poole-Wilson, PA U1 - Workshop on Surgical Remodeling in Heart Failure - Alternative to Transplantation Y1 - 2000/// Y2 - // SP - 19 EP - 30 N2 - - ER - TY - CONF T1 - The role of eotaxin and related CC-chemokines in asthma and allergy A1 - Mitchell, TJ A1 - Williams, TJ U1 - 9th International Conference of the Inflammation Association Y1 - 2000/// Y2 - // SP - 1 EP - 12 N2 - - ER - TY - CONF T1 - Non-contact mapping of the human left atrium to guide ablation of focal atrial fibrillation A1 - Markides, V A1 - Schilling, RJ A1 - Chow, AWC A1 - Kanagaratnam, P A1 - Lamb, D A1 - Peters, NS A1 - Davies, DW U1 - 27th Annual Meeting of Computers in Cardiology Y1 - 2000/// Y2 - // VL - 27 SP - 89 EP - 91 N2 - - ER - TY - CONF T1 - Delineation of the patterns of activation of the human left atrium during sinus rhythm using a non-contact mapping system A1 - Markides, V A1 - Schilling, RJ A1 - Chow, AWC A1 - Lamb, D A1 - Kanagaratnam, P A1 - Davies, DW A1 - Peters, NS U1 - 27th Annual Meeting of Computers in Cardiology Y1 - 2000/// Y2 - // VL - 27 SP - 497 EP - 498 N2 - - ER - TY - CONF T1 - Secondary prevention: pharmacology A1 - Schachter, M U1 - Symposium on Key Advances in the Effective Management of Myocardial Infarction Y1 - 1999/// Y2 - // SP - 39 EP - 44 N2 - - ER - TY - CONF T1 - Action of specific estrogens on vascular cells A1 - Wingrove, CS A1 - Stevenson, JC U1 - 3rd International Symposium on Womens Health and Menopause Y1 - 1999/// Y2 - // VL - 13 SP - 53 EP - 58 N2 - - ER - TY - CONF T1 - The convergence technique in numerical solutions of coupled fluid-wall problems A1 - Zhao, SZ A1 - Xu, XY A1 - Collins, MW A1 - Stanton, AV A1 - Hughes, AD A1 - Thom, SA U1 - Conference on Cardiovascular Flow Modelling and Measurement with Application to Clinical Medicine Y1 - 1999/// Y2 - // VL - 70 SP - 125 EP - 134 N2 - - ER - TY - CONF T1 - The effect of estrogen on the coronary vasculature A1 - Collins, P U1 - 1st International Symposium on Estrogens and the Cardiovascular Systems Y1 - 1999/// Y2 - // SP - 21 EP - 31 N2 - - ER - TY - CONF T1 - Allogeneic and xenogeneic interactions between endothelial cells and human T cells during transplant rejection A1 - Rose, ML U1 - Conference on the Nato Advanced Study Institute on Vasclar Endothelium - Mechanisms of Cell Signaling Y1 - 1999/// Y2 - // VL - 308 SP - 33 EP - 47 N2 - - ER - TY - CONF T1 - Reduced FOV imaging with motion adaptation A1 - Yang, GZ A1 - Gatehouse, PD A1 - Firmin, DN U1 - 7th IEE Conference on Image Processing and its Applications (IPA99) Y1 - 1999/// Y2 - // SP - 502 EP - 506 N2 - - ER - TY - CONF T1 - Simultaneous localization of connexins 40, 37 and 43 in pulmonary artery endothelial gap junctions A1 - Ko, YS A1 - Yey, HI A1 - Rothery, S A1 - Dupont, E A1 - Severs, NJ U1 - 8th International Gap Junction Conference Y1 - 1998/// Y2 - // SP - 183 EP - 187 N2 - - ER - TY - CONF T1 - T lymphocytes in chronic asthma A1 - Kay, AB U1 - 5th International Conference on Asthma Y1 - 1998/// Y2 - // SP - 207 EP - 221 N2 - - ER - TY - CONF T1 - Transcription factors in asthma A1 - Adcock, IM A1 - Barnes, PJ U1 - 5th International Conference on Asthma Y1 - 1998/// Y2 - // SP - 25 EP - 45 N2 - - ER - TY - CONF T1 - Effects of caval velocity profiles on pulmonary flow in the total cavopulmonary connection: CFD 3-D model and magnetic resonance studies A1 - Migliavacca, F A1 - Pennati, G A1 - Dubini, G A1 - Pietrabissa, R A1 - Fumero, R A1 - Kilner, PJ A1 - de Leval, MR U1 - 3rd International Symposium on Computer Methods in Biomechanics and Biomedical Engineering Y1 - 1998/// Y2 - // SP - 601 EP - 608 N2 - - ER - TY - CONF T1 - Increased levels of markers of protein oxidation in bronchoalveolar lavage fluid from patients with ARDS A1 - Quinlan, GJ A1 - Lamb, NJ A1 - Evans, TW A1 - Gutteridge, JMC U1 - NATO Advanced Study Institute on Acute Respiratory Distress Syndrome - Cellular and Molecular Mechanisms and Clinical Management Y1 - 1998/// Y2 - // VL - 297 SP - 263 EP - 264 N2 - - ER - TY - CONF T1 - Nitric oxide in asthma A1 - Chung, KF U1 - 5th West-Pacific Allergy Symposium/7th Korea-Japan Joint Allergy Symposium Y1 - 1997/// Y2 - // SP - 53 EP - 60 N2 - - ER - TY - CONF T1 - Towards retinal vessel paramaterisation A1 - Xiaohong,G.X. A1 - Bharath,A.A. A1 - Hughes,A.D. A1 - Stanton,A.V. A1 - Chapman,N. A1 - Thom,S.A. U1 - SPIE Conference on Medical Imaging Y1 - 1997/// N2 - - ER - TY - CONF T1 - Neurogenic mechanisms in asthma A1 - Chung, KF U1 - 5th West-Pacific Allergy Symposium/7th Korea-Japan Joint Allergy Symposium Y1 - 1997/// Y2 - // SP - 129 EP - 136 N2 - - ER - TY - CONF T1 - Functional microanatomy of the cardiac muscle cell and its gap junctions A1 - Severs, NJ U1 - 2nd International Malpighi Symposium on Recent Advances in Microscopy of Cells Tissues and Organs Y1 - 1997/// Y2 - // SP - 281 EP - 290 N2 - - ER - TY - CONF T1 - The anatomy and innervation of the conduction system A1 - Crick, SJ A1 - Sheppard, MN A1 - Ho, SY A1 - Anderson, RH U1 - 2nd International Malpighi Symposium on Recent Advances in Microscopy of Cells Tissues and Organs Y1 - 1997/// Y2 - // SP - 301 EP - 309 N2 - - ER - TY - CONF T1 - Hormone replacement therapy in diabetes A1 - Stevenson, JC A1 - Godsland, IF U1 - 8th International Congress on the Menopause Y1 - 1997/// Y2 - // SP - 315 EP - 322 N2 - - ER - TY - CONF T1 - HRT and the secondary prevention of coronary heart disease A1 - Stevenson, JC U1 - 2nd International Symposium on Womens Health in Menopause - Risk Reduction Strategies Y1 - 1997/// Y2 - // VL - 11 SP - 125 EP - 128 N2 - - ER - TY - JFULL T1 - Elevated Factor VIII in hereditary haemorrhagic telangiectasia (HHT): association with venous thromboembolism A1 - Shovlin, CL A1 - Sulainam, N A1 - Govani, FS A1 - Jackson , JE A1 - Begbie, ME J1 - Thrombosis and Haemostasis Y1 - 2007/11// ER - TY - JFULL T1 - Elevated Factor VIII in hereditary haemorrhagic telangiectasia (HHT): association with venous thromboembolism A1 - Shovlin, C L A1 - Sulainam, N L A1 - Govani, FS A1 - Jackson, JE A1 - Begbie, ME J1 - Thrombosis and Haemostasis Y1 - 2007/11// N2 - Introduction: Hereditary haemorrhagic telangiectasia (HHT) causes chronic nasal and gastrointestinal haemorrhage. Prothrombotic agents are commonly used for severe haemorrhage. Thrombotic risks have not been defined. Methods To identify prothrombotic variables in HHT patients, and assess their potential functional significance, a pilot ELISA-based study comparing plasma proteins in healthy individuals with HHT to age/sex-matched non-HHT controls was validated in a full study of 309 consecutive HHT-affected individuals. Results In the pilot study, Factor VIII (FVIII) and Von Willebrand Factor antigen concentrations were elevated in the HHT group compared to non-HHT controls (p0.0013, Mann-Whitney). Service laboratory measurements confirmed high FVIII:Ag in 125 HHT-affected individuals with no recent ill-health, intervention or venous thromboemboli. FVIII:Ag levels increased with age. Logistic regression also suggested an age-independent association with HHT-associated pulmonary arteriovenous malformations (PAVMs). No association was demonstrated between FVIII:Ag and acute phase response, disseminated intravascular coagulation, ABO group, pulmonary artery pressure, or markers of HHT haemorrhage. Elevated FVIII:Ag were associated with shortened activated partial thromboplastin times (APTTs), and VTE: VTE affected 20/309 (6.5%) HHT-affected individuals, at median age 61(36-71)yr. Four VTE occurred in Factor V Leiden heterozygotes in the months following PAVM-associated brain abscess. The strongest association with VTE was with log-transformed FVIII:Ag measured 10-132 months from VTE (odds ratio 2.41 (95% confidence intervals 1.254, 4.612, p=0.008). Age made no additional contribution to VTE risk once adjusted for FVIII:Ag. Conclusions HHT-related elevation of FVIII:Ag levels may influence thrombotic risk in HHT. Individualised risk-benefit considerations may be helpful in the management of individuals with HHT. ER - TY - JFULL T1 - Primary ciliary dyskinesia in the paediatric population: range and severity of radiological findings in a cohort of patients receiving tertiary care. A1 - Jain, K A1 - Padley, SP A1 - Goldstraw, EJ A1 - Kidd, SJ A1 - Hogg, C A1 - Biggart, E A1 - Bush, A J1 - Clin Radiol Y1 - 2007/10// VL - 62 SN - 0009-9260 SP - 986 EP - 993 N2 - AIM: To investigate the clinical range and severity of radiological findings in a cohort of patients with primary ciliary dyskinesia (PCD) receiving tertiary care. MATERIALS AND METHODS: The case notes and clinical test results of 89 children attending the paediatric respiratory disease clinic at our institution were retrospectively analysed. Demographic details including age at diagnosis and common presenting signs and symptoms were studied. Results of chest radiographs, microscopy, and high-resolution computed tomography (HRCT) for quantification of lung damage were analysed. RESULTS: In a cohort of 89 children with PCD, a presentation chest radiograph was available in 62% of patients (n=55), with all but one demonstrating changes of bronchial wall thickening. HRCT of the lungs, available in 26 patients, were scored using the system described by Brody et al. analysing five specific features of lung disease, including bronchiectasis, mucus plugging, peribronchial thickening, parenchymal changes of consolidation, and ground-glass density, and focal air-trapping in each lobe. Peribronchial thickening was observed using HRCT in 25 patients, while 20 patients had bronchiectasis. Severity scores were highest for the middle and the lingular lobes. CONCLUSION: The radiographic findings of the largest reported cohort of patients with PCD are presented, with associated clinical findings. Dextrocardia remains the commonest finding on chest radiography. HRCT demonstrates peribronchial thickening and bronchiectasis, which is most marked in the lower zones. Radiological scoring techniques developed for assessment of cystic fibrosis can also be applied for the assessment of disease severity in this patient population. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17765464&query_hl=1 ER - TY - JFULL T1 - Oestrogen directly inhibits the cardiovascular L-type Ca(2+) channel Ca(v)1.2. A1 - Ullrich, ND A1 - Koschak, A A1 - Macleod, KT J1 - Biochem Biophys Res Commun Y1 - 2007/09/21/ VL - 361 SN - 0006-291X SP - 522 EP - 527 N2 - Oestrogen can modify the contractile function of vascular smooth muscle and cardiomyocytes. The negative inotropic actions of oestrogen on the heart and coronary vasculature appear to be mediated by L-type Ca(2+) channel (Ca(v)1.2) inhibition, but the underlying mechanisms remain elusive. We tested the hypothesis that oestrogen directly inhibits the cardiovascular L-type Ca(2+) current, I(CaL). The effect of oestrogen on I(CaL) was measured in Ca(v)1.2-transfected HEK-293 cells using the whole-cell patch-clamp technique. The current revealed typical activation and inactivation profiles of nifedipine- and cadmium-sensitive I(CaL). Oestrogen (50muM) rapidly reduced I(CaL) by 50% and shifted voltage-dependent activation and availability to more negative potentials. Furthermore, oestrogen blocked the Ca(2+) channel in a rate-dependent way, exhibiting higher efficiency of block at higher stimulation frequencies. Our data suggest that oestrogen inhibits I(CaL) through direct interaction of the steroid with the channel protein. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17662243&query_hl=1 ER - TY - JFULL T1 - Atopic sensitization and the international variation of asthma symptom prevalence in children. A1 - Weinmayr, G A1 - Weiland, SK A1 - Björkstén, B A1 - Brunekreef, B A1 - Büchele, G A1 - Cookson, WO A1 - Garcia-Marcos, L A1 - Gotua, M A1 - Gratziou, C A1 - van Hage, M A1 - von Mutius, E A1 - Riikjärv, MA A1 - Rzehak, P A1 - Stein, RT A1 - Strachan, DP A1 - Tsanakas, J A1 - Wickens, K A1 - Wong, GW A1 - and the ISAAC Phase Two Study Group J1 - Am J Respir Crit Care Med Y1 - 2007/09/15/ VL - 176 SN - 1073-449X SP - 565 EP - 574 N2 - Rationale: Atopic sensitization has long been known to be related to asthma in children, but its role in determining asthma prevalence remains to be elucidated further. Objectives: To investigate the role of atopic sensitization in the large international variation in the prevalence of childhood asthma. Methods: Cross-sectional studies of random samples of 8- to 12-year-old children (n = 1,000 per center) were performed according to the standardized methodology of Phase Two of the International Study of Asthma and Allergy in Childhood (ISAAC). Thirty study centers in 22 countries worldwide participated and reflect a wide range of living conditions, from rural Africa to urban Europe. Data were collected by parental questionnaires (n = 54,439), skin prick tests (n = 31,759), and measurements of allergen-specific IgE levels in serum (n = 8,951). Economic development was assessed by gross national income per capita (GNI). Measurements and Main Results: The prevalence of current wheeze (i.e., during the past year) ranged from 0.8% in Pichincha (Ecuador) to 25.6% in Uruguaiana (Brazil). The fraction of current wheeze attributable to atopic sensitization ranged from 0% in Ankara (Turkey) to 93.8% in Guangzhou (China). There were no correlations between prevalence rates of current wheeze and atopic sensitization, and only weak correlations of both with GNI. However, the fractions and prevalence rates of wheeze attributable to skin test reactivity correlated strongly with GNI (Spearman rank-order coefficient rho = 0.50, P = 0.006, and rho = 0.74, P < 0.0001, respectively). In addition, the strength of the association between current wheeze and skin test reactivity, assessed by odds ratios, increased with GNI (rho = 0.47, P = 0.01). Conclusions: The link between atopic sensitization and asthma symptoms in children differs strongly between populations and increases with economic development. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17575099&query_hl=1 ER - TY - JFULL T1 - Fluorescence lifetime imaging to detect actomyosin States in Mammalian muscle sarcomeres. A1 - García, DI A1 - Lanigan, P A1 - Webb, M A1 - West, TG A1 - Requejo-Isidro, J A1 - Auksorius, E A1 - Dunsby, C A1 - Neil, M A1 - French, P A1 - Ferenczi, MA J1 - Biophys J Y1 - 2007/09/15/ VL - 93 SN - 0006-3495 SP - 2091 EP - 2101 N2 - We investigated the use of fluorescence lifetime imaging microscopy (FLIM) of a fluorescently labeled ATP analog (3'-O-{N-[3-(7-diethylaminocoumarin-3-carboxamido)propyl]carbamoyl}ATP) to probe in permeabilized muscle fibers the changes in the environment of the nucleotide binding pocket caused by interaction with actin. Spatial averaging of FLIM data of muscle sarcomeres reduces photon noise, permitting detailed analysis of the fluorescence decay profiles. FLIM reveals that the lifetime of the nucleotide, in its ADP form because of the low concentration of nucleotide present, changes depending on whether the nucleotide is free in solution or bound to myosin, and on whether the myosin is bound to actin in an actomyosin complex. Characterization of the fluorescence decays by a multiexponential function allowed us to resolve the lifetimes and amplitudes of each of these populations, namely, the fluorophore bound to myosin, bound to actin, in an actomyosin complex, and free in the filament lattice. This novel application of FLIM to muscle fibers shows that with spatial averaging, detailed information about the nature of nucleotide complexes can be derived. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17496049&query_hl=1 ER - TY - JFULL T1 - JAM-A mediates neutrophil transmigration in a stimulus-specific manner in vivo: evidence for sequential roles for JAM-A and PECAM-1 in neutrophil transmigration. A1 - Woodfin, A A1 - Reichel, CA A1 - Khandoga, A A1 - Corada, M A1 - Voisin, MB A1 - Scheiermann, C A1 - Haskard, DO A1 - Dejana, E A1 - Krombach, F A1 - Nourshargh, S J1 - Blood Y1 - 2007/09/15/ VL - 110 SN - 0006-4971 SP - 1848 EP - 1856 N2 - Junctional adhesion molecule-A (JAM-A) is a transmembrane protein expressed at tight junctions of endothelial and epithelial cells and on the surface of platelets and leukocytes. The role of JAM-A in leukocyte transmigration in vivo was directly investigated by intravital microscopy using both a JAM-A-neutralizing monoclonal antibody (mAb) (BV-11) and JAM-A-deficient (knockout [KO]) mice. Leukocyte transmigration (but not adhesion) through mouse cremasteric venules as stimulated by interleukin 1beta (IL-1beta) or ischemia/reperfusion (I/R) injury was significantly reduced in wild-type mice treated with BV-11 and in JAM-A KO animals. In contrast, JAM-A blockade/genetic deletion had no effect on responses elicited by leukotriene B(4) (LTB(4)) or platelet-activating factor (PAF). Furthermore, using a leukocyte transfer method and mice deficient in endothelial-cell JAM-A, evidence was obtained for the involvement of endothelial-cell JAM-A in leukocyte transmigration mediated by IL-1beta. Investigation of the functional relationship between JAM-A and PECAM-1 (CD31) determined that dual blockade/deletion of these proteins does not lead to an inhibitory effect greater than that seen with blockade/deletion of either molecule alone. The latter appeared to be due to the fact that JAM-A and PECAM-1 can act sequentially to mediate leukocyte migration through venular walls in vivo. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17505016&query_hl=1 ER - TY - JFULL T1 - A protein kinase Cepsilon /anti-apoptotic kinase signalling complex protects human vascular endothelial cells against apoptosis through induction of Bcl-2. A1 - Steinberg, R A1 - Harari, OA A1 - Lidington, EA A1 - Boyle, JJ A1 - Nohadani, M A1 - Samarel, AM A1 - Ohba, M A1 - Haskard, DO A1 - Mason, JC J1 - J Biol Chem Y1 - 2007/09/04/ SN - 0021-9258 N2 - Endothelial cell apoptosis is associated with vascular injury and predisposes to atherogenesis. EC express anti-apoptotic genes including Bcl-2, Bcl-X(L) and survivin, which also contribute to angiogenesis and vascular remodelling. We report a central role for PKCepsilon in the regulation of Bcl-2 expression and cytoprotection of human vascular endothelium against apoptosis. Using myristoylated inhibitory peptides, a predominant role for PKCepsilon in VEGF-mediated endothelial resistance to apoptosis was revealed. Immunoblotting of endothelial cells infected with an adenovirus expressing a constitutively-active form of PKCepsilon (Adv-PKCepsilon-CA) or control Adv-beta-gal demonstrated a 3-fold, PKCepsilon-dependent increase in Bcl-2 expression, with no significant change in Bcl-X(L), Bad, Bak or Bax. The induction of Bcl-2 inhibited apoptosis induced by serum starvation or etoposide, and PKCepsilon activation attenuated etoposide-induced caspase-3 cleavage. The functional role of Bcl-2 was confirmed with Bcl-2 antagonist HA-14-1. Inhibition of PI-3K attenuated VEGF-induced protection against apoptosis and this was rescued by over-expression of CA-PKCepsilon, suggesting PKCepsilon acts downstream of PI-3K. Co-immunoprecipitation studies demonstrated a physical interaction between PKCepsilon and Akt, which resulted in formation of a signaling complex, leading to optimal induction of Bcl-2. This study reveals a pivotal role for PKCepsilon in endothelial cell cytoprotection against apoptosis. We demonstrate that PKCepsilon forms a signalling complex and acts co-operatively with Akt to protect human vascular endothelial cells against apoptosis, through induction of the anti-apoptotic protein Bcl-2 and inhibition of caspase-3 cleavage. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17785460&query_hl=1 ER - TY - JFULL T1 - Should beta-blocker therapy be reduced or withdrawn after an episode of decompensated heart failure? Results from COMET. A1 - Metra, M A1 - Torp-Pedersen, C A1 - Cleland, JG A1 - Di Lenarda, A A1 - Komajda, M A1 - Remme, WJ A1 - Dei Cas, L A1 - Spark, P A1 - Swedberg, K A1 - Poole-Wilson, PA A1 - for the COMET investigators J1 - Eur J Heart Fail Y1 - 2007/09// VL - 9 SN - 1388-9842 SP - 901 EP - 909 N2 - BACKGROUND: It is unclear whether beta-blocker therapy should be reduced or withdrawn in patients who develop acute decompensated heart failure (HF). We studied the relationship between changes in beta-blocker dose and outcome in patients surviving a HF hospitalisation in COMET. METHODS: Patients hospitalised for HF were subdivided on the basis of the beta-blocker dose administered at the visit following hospitalisation, compared to that administered before. RESULTS: In COMET, 752/3029 patients (25%, 361 carvedilol and 391 metoprolol) had a non-fatal HF hospitalisation while on study treatment. Of these, 61 patients (8%) had beta-blocker treatment withdrawn, 162 (22%) had a dose reduction and 529 (70%) were maintained on the same dose. One-and two-year cumulative mortality rates were 28.7% and 44.6% for patients withdrawn from study medication, 37.4% and 51.4% for those with a reduced dosage (n.s.) and 19.1% and 32.5% for those maintained on the same dose (HR,1.59; 95%CI, 1.28-1.98; p<0.001, compared to the others). The result remained significant in a multivariable model: (HR, 1.30; 95%CI, 1.02-1.66; p=0.0318). No interaction with the beneficial effects of carvedilol, compared to metoprolol, on outcome was observed (p=0.8436). CONCLUSIONS: HF hospitalisations are associated with a high subsequent mortality. The risk of death is higher in patients who discontinue beta-blocker therapy or have their dose reduced. The increase in mortality is only partially explained by the worse prognostic profile of these patients. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17581778&query_hl=1 ER - TY - JFULL T1 - Rab27a and MyoVa are the primary Mlph interactors regulating melanosome transport in melanocytes. A1 - Hume, AN A1 - Ushakov, DS A1 - Tarafder, AK A1 - Ferenczi, MA A1 - Seabra, MC J1 - J Cell Sci Y1 - 2007/09/01/ VL - 120 SN - 0021-9533 SP - 3111 EP - 3122 N2 - Melanosome transport in melanocytes is a model system for the study of cytoskeletal regulation of intracellular transport. Melanophilin (Mlph) is a Rab27a- and myosin Va (MyoVa)-binding protein that regulates this process. Using yeast two-hybrid screening, we identified MT plus-end binding protein (EB1) as a melanocyte-expressed Mlph-interacting protein. To address the role of EB1 versus Rab27a and MyoVa interactions in Mlph targeting and function, we used siRNA and Mlph mutations to specifically disrupt each interaction in cultured melanocytes. Using the Mlph R35W mutant that blocks Mlph-Rab27a interaction and Rab27a siRNA we show this interaction is required for melanosome targeting and stability of Mlph. Mutants and siRNA that affect Mlph-MyoVa and Mlph-EB1 interactions reveal that while neither MyoVa nor EB1 affect Mlph targeting to melanosomes, MyoVa but not EB1 interaction is required for transport of melanosomes to peripheral dendrites. We propose that Mlph is targeted to and/or stabilised on melanosomes by Rab27a, and then recruits MyoVa, which provides additional stability to the complex and allows melanosomes to transfer from MT to actin-based transport and achieve peripheral distribution. EB1 appears to be non-essential to this process in cultured melanocytes, which suggests that it plays a redundant role and/or is required for melanocyte/keratinocyte contacts and melanosome transfer. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17698919&query_hl=1 ER - TY - JFULL T1 - An unusual case of cardiac amyloidosis. A1 - Bucciarelli-Ducci, C A1 - Pennell, DJ J1 - J Gen Intern Med Y1 - 2007/09// VL - 22 SN - 1525-1497 SP - 1382 EP - 1382 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17632762&query_hl=1 ER - TY - JFULL T1 - Physiology of airway mucus secretion and pathophysiology of hypersecretion. A1 - Rogers, DF J1 - Respir Care Y1 - 2007/09// VL - 52 SN - 0020-1324 SP - 1134 EP - 1149 N2 - Mucus secretion is the first-line defense against the barrage of irritants that inhalation of approximately 500 L of air an hour brings into the lungs. The inhaled soot, dust, microbes, and gases can all damage the airway epithelium. Consequently, mucus secretion is extremely rapid, occurring in tens of milliseconds. In addition, mucus is held in cytoplasmic granules in a highly condensed state in which high concentrations of Ca(2+) nullify the repulsive forces of the highly polyanionic mucin molecules. Upon initiation of secretion and dilution of the Ca(2+), the repulsion forces of the mucin molecules cause many-hundred-fold swelling of the secreted mucus, to cover and protect the epithelium. Secretion is a highly regulated process, with coordination by several molecules, including soluble N-ethyl-maleimide-sensitive factor attachment protein receptor (SNARE) proteins, myristoylated alanine-rich C kinase substrate (MARCKS), and Munc proteins, to dock the mucin granules to the secretory cell membrane prior to exocytosis. Because mucus secretion appears to be such a fundamental airway homeostatic process, virtually all regulatory and inflammatory mediators and interventions that have been investigated increase secretion acutely. When given longer-term, many of these same mediators also increase mucin gene expression and mucin synthesis, and induce goblet cell hyperplasia. These responses induce (in contrast to the protective effects of acute secretion) long-term, chronic hypersecretion of airway mucus, which contributes to respiratory disease. In this case the homeostatic, protective function of airway mucus secretion is lost, and, instead, mucus hypersecretion contributes to pathophysiology of a number of severe respiratory conditions, including asthma, chronic obstructive pulmonary disease, and cystic fibrosis. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17716382&query_hl=1 ER - TY - JFULL T1 - Myocardial tissue characterization and the role of chronic anemia in sickle cell cardiomyopathy. A1 - Westwood, MA A1 - Shah, F A1 - Anderson, LJ A1 - Strange, JW A1 - Tanner, MA A1 - Maceira, AM A1 - Howard, J A1 - John B. Porter A1 - Walker, JM A1 - Wonke, B A1 - Pennell, DJ J1 - J Magn Reson Imaging Y1 - 2007/09// VL - 26 SN - 1053-1807 SP - 564 EP - 568 N2 - PURPOSE: To use cardiovascular magnetic resonance (CMR) techniques to examine possible causes for the left ventricular (LV) dilatation that occurs in sickle cell disease (SCD), including the effects of chronic anemia, iron-induced cardiomyopathy, and regional fibrosis due to sludge infarcts that occur during sickle crises. MATERIALS AND METHODS: A total of 47 patients with sickle cell anemia were assessed for LV function and myocardial iron levels using CMR measurements; 30 of these were also assessed for regional fibrosis using late gadolinium-enhancement CMR. The LV function was compared to both normal controls and transfusion dependent non-iron-loaded (NIL) thalassemia major (TM) patients. RESULTS: Only one SCD patient had significant myocardial iron loading, and only two patients had regional fibrosis. There were significant differences in ventricular volumes of the sickle patients compared with both the normal controls and the NIL-TM population (P < 0.01). CONCLUSION: The LV changes seen in SCD are partly the result of a chronic anemia but there appears to be another contributory factor. This extra factor is not myocardial iron loading or regional fibrosis, although a homogenous fibrotic disorder affecting the left ventricle cannot be excluded. J. Magn. Reson. Imaging 2007;26:564-568. (c) 2007 Wiley-Liss, Inc. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17729345&query_hl=1 ER - TY - JFULL T1 - Mucoactive agents for airway mucus hypersecretory diseases. A1 - Rogers, DF J1 - Respir Care Y1 - 2007/09// VL - 52 SN - 0020-1324 SP - 1176 EP - 1197 N2 - Airway mucus hypersecretion is a feature of a number of severe respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF). However, each disease has a different airway inflammatory response, with consequent, and presumably linked, mucus hypersecretory phenotype. Thus, it is possible that optimal treatment of the mucus hypersecretory element of each disease should be disease-specific. Nevertheless, mucoactive drugs are a longstanding and popular therapeutic option, and numerous compounds (eg, N-acetylcysteine, erdosteine, and ambroxol) are available for clinical use worldwide. However, rational recommendation of these drugs in guidelines for management of asthma, COPD, or CF has been hampered by lack of information from well-designed clinical trials. In addition, the mechanism of action of most of these drugs is unknown. Consequently, although it is possible to categorize them according to putative mechanisms of action, as expectorants (aid and/or induce cough), mucolytics (thin mucus), mucokinetics (facilitate cough transportability), and mucoregulators (suppress mechanisms underlying chronic mucus hypersecretion, such as glucocorticosteroids), it is likely that any beneficial effects are due to activities other than, or in addition to, effects on mucus. It is also noteworthy that the mucus factors that favor mucociliary transport (eg, thin mucus gel layer, "ideal" sol depth, and elasticity greater than viscosity) are opposite to those that favor cough effectiveness (thick mucus layer, excessive sol height, and viscosity greater than elasticity), which indicates that different mucoactive drugs would be required for treatment of mucus obstruction in proximal versus distal airways, or in patients with an impaired cough reflex. With the exception of mucoregulatory agents, whose primary action is unlikely to be directed against mucus, well-designed clinical trials are required to unequivocally determine the effectiveness, or otherwise, of expectorant, mucolytic, and mucokinetic agents in airway diseases in which mucus hypersecretion is a pathophysiological and clinical issue. It is noteworthy that, of the more complex molecules in development, it is simple inhaled hypertonic saline that is currently receiving the greatest attention as a mucus therapy, primarily in CF. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17716385&query_hl=1 ER - TY - JFULL T1 - A novel technique for nonvolitional assessment of quadriceps muscle endurance in humans. A1 - Swallow, EB A1 - Gosker, HR A1 - Ward, KA A1 - Moore, AJ A1 - Dayer, MJ A1 - Hopkinson, NS A1 - Schols, AM A1 - Moxham, J A1 - Polkey, MI J1 - J Appl Physiol Y1 - 2007/09// VL - 103 SN - 8750-7587 SP - 739 EP - 746 N2 - Assessment of quadriceps endurance is of interest to investigators studying human disease. We hypothesized that repetitive magnetic stimulation (rMS) of the intramuscular branches of the femoral nerve could be used to induce and quantify quadriceps endurance. To test this hypothesis, we used a novel stimulating coil to compare the quadriceps endurance properties in eight normal humans and, to confirm that the technique could be used in clinical practice, in eight patients with advanced chronic obstructive pulmonary disease (COPD). To validate the method, we compared in vivo contractile properties of the quadriceps muscle with the fiber-type composition and oxidative enzyme capacity. We used a Magstim Rapid(2) magnetic nerve stimulator with the coil wrapped around the quadriceps. Stimuli were given at 30 Hz, a duty cycle of 0.4 (2 s on, 3 s off), and for 50 trains. Force generation and the surface electromyogram were measured throughout. Quadriceps twitch force, elicited by supramaximal magnetic stimulation of the femoral nerve, was measured before and after the protocol. Quadriceps muscle biopsies were analyzed for oxidative (citrate synthase, CS) and glycolytic (phosphofructokinase, PFK) enzyme activity and myosin heavy chain isoform protein expression. The time for force to fall to 70% of baseline (T(70)) was shorter in the COPD group than the control group: 55.6 +/- 26.0 vs. 121 +/- 38.7 s (P = 0.0014). Considering patients and controls together, positive correlations were observed between T(70) and the proportion of type I fibers (r = 0.68, P = 0.004) and CS-to-PFK ratio (CS/PFK) (r = 0.67, P = 0.005). We conclude that quadriceps endurance assessed using rMS is feasible in clinical studies. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17569771&query_hl=1 ER - TY - JFULL T1 - Factors effecting impact of Aspergillus fumigatus sensitization in cystic fibrosis. A1 - Kanthan, SK A1 - Bush, A A1 - Kemp, M A1 - Buchdahl, R J1 - Pediatr Pulmonol Y1 - 2007/09// VL - 42 SN - 8755-6863 SP - 785 EP - 793 N2 - The clinical impact of Aspergillus fumigatus (Af) sensitization in cystic fibrosis (CF) is controversial. We examined the effect of Af sensitization (Afs) on pulmonary function and growth using a retrospective cohort analysis over two 5-year study periods: 1996-2000 (19 Afs cases and 19 controls) and 2001-2005 (24 Afs cases and 23 controls). Sensitization was defined as Af specific radioallergosorbent test (RAST) >/= 17.5 iu/ml and total serum IgE level >/=150 iu/ml. We examined the impact of changing treatment schedules over these periods. Afs cases had lower median FEV(1) %predicted (%PR) compared to matched controls 1996: 67 versus 80, P < 0.01; 2001: 78 versus 93, P < 0.01. Afs cases in the 2001 cohort had a higher FEV(1) %PR compared to Afs cases in the 1996 cohort: 78 versus 67, P < 0.01. For the 1996 Afs cohort FEV(1) %PR fell significantly over 5 years but not for the 2001 Afs cohort. Af RAST and total IgE reflected the changes in pulmonary function. Children in the 2001 Afs cohort were prescribed significantly more oral antifungal treatment (odds ratio 4.3, 95%CI 1.2-15.7, P = 0.03). Afs children continue to have poorer lung function compared to controls but this observational, hypothesis generating study, suggests that the use of antifungal treatment is associated with better lung function. Pediatr Pulmonol. 2007; 42:785-793. (c) 2007 Wiley-Liss, Inc. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17659599&query_hl=1 ER - TY - JFULL T1 - Airway hyperresponsiveness and bronchial mucosal inflammation in T cell peptide-induced asthmatic reactions in atopic subjects. A1 - Ali, FR A1 - Kay, AB A1 - Larché, M J1 - Thorax Y1 - 2007/09// VL - 62 SN - 0040-6376 SP - 749 EP - 756 N2 - BACKGROUND: Subjects with allergic asthma develop isolated late asthmatic reactions after inhalation of allergen-derived T cell peptides. Animal experiments have shown that airway hyperresponsiveness (AHR) is CD4+ cell-dependent. It is hypothesised that peptide inhalation produces increases in non-specific AHR and a T cell-dominant bronchial mucosal inflammatory response. METHODS: Bronchoscopy, with bronchial biopsies and bronchoalveolar lavage (BAL), was performed in 24 subjects with cat allergy 6 h after aerosol inhalation of short overlapping peptides derived from Fel d 1, the major cat allergen. Biopsy specimens and BAL fluid were studied using immunohistochemistry and ELISA. RESULTS: Twelve of the 24 subjects developed an isolated late asthmatic reaction without a preceding early (mast cell/histamine-dependent) reaction characteristic of whole allergen inhalation. These responders had significant between-group differences (responders vs non-responders) in the changes (peptide vs diluent) in AHR (p = 0.007) and bronchial mucosal CD3+ (p = 0.005), CD4+ (p = 0.006) and thymus- and activation-regulated chemokine (TARC)+ (p = 0.003) but not CD8+ or CD25+ cells or eosinophils, basophils, mast cells and macrophages. The between-group difference for neutrophils was p = 0.05 but with a non-significant within-group value (peptide vs diluent, responders, p = 0.11). In BAL fluid there was a significant between-group difference in TARC (p = 0.02) but not in histamine, tryptase, basogranulin, C3a or C5a, leukotrienes C(4)/D(4)/E(4), prostaglandins D(2) or F(2alpha). CONCLUSIONS: Direct activation of allergen-specific airway T cells by peptide inhalation in patients with atopic asthma leads to increased AHR with local increases in CD3+ and CD4+ cells and TARC but no significant changes in eosinophils or basophil/mast cell products. These findings support previous animal experiments which showed a CD4+ dependence for AHR. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17389757&query_hl=1 ER - TY - JFULL T1 - Src family tyrosine kinases mediate contraction of rat isolated tail arteries in response to a hyposmotic stimulus. A1 - Wijetunge, S A1 - Hughes, AD J1 - J Hypertens Y1 - 2007/09// VL - 25 SN - 0263-6352 SP - 1871 EP - 1878 N2 - OBJECTIVE: Hypotonic solutions cause vasoconstriction in rat tail arteries, due largely to activation of L-type calcium channels (CaV1.2). We studied possible roles of tyrosine kinases, particularly src family kinases (SFK) and extracellular signal-related kinases (ERK1/2), in this response. METHODS: Rat tail arteries were mounted on a myograph for measurement of isometric force. Arteries were bathed in isosmotic physiological saline solution (300 mOsm/l) containing 50 mmol/l mannitol and were stimulated by a hyposmotic solution containing 0 mmol/l mannitol (PSS-M). Activation of tyrosine kinases and ERK1/2 by hyposmotic solution was examined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and western blotting on rat tail artery lysates with specific phospho-antibodies. RESULTS: Western blotting showed SFK src and yes present in rat tail artery. PSS-M increased tyrosine phosphorylation of several proteins, including SFK and ERK1/2. Genistein blocked phosphorylation of SFK and ERK1/2 by PSS-M. In isolated arteries PSS-M caused a contraction inhibited by the tyrosine kinase inhibitor, genistein, and three structurally different selective SFK inhibitors, herbimycin-A, PP1 and SU6656. Mitogen-activated protein kinase kinase inhibitor PD98059 or selective inhibitors of platelet-derived growth factor receptor (AG1296) and epidermal growth factor receptor (AG1478) had no effect on contraction induced by a hypotonic solution. CONCLUSIONS: Hyposmotic conditions activate SFK, src and yes, and contract rat tail artery by a SFK-dependent mechanism. ERK1/2 are activated by the hypotonic solution, but do not play a role in the contractile response. SFK modulation of CaV1.2 may be an important mechanism mediating vasoconstriction to mechanical stimuli in vascular smooth muscle. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17762651&query_hl=1 ER - TY - JFULL T1 - Analysis of BTNL2 genetic polymorphisms in British and Dutch patients with sarcoidosis. A1 - Spagnolo, P A1 - Sato, H A1 - Grutters, JC A1 - Renzoni, EA A1 - Marshall, SE A1 - Ruven, HJ A1 - Wells, AU A1 - Tzouvelekis, A A1 - van Moorsel, CH A1 - van den Bosch, JM A1 - du Bois, RM A1 - Welsh, KI J1 - Tissue Antigens Y1 - 2007/09// VL - 70 SN - 0001-2815 SP - 219 EP - 227 N2 - Sarcoidosis is a heterogeneous disorder, both phenotypically and genetically. Two independent studies have recently shown that a functional polymorphism within butyrophilin-like 2 (BTNL2) gene predisposes to sarcoidosis independently of the human leukocyte antigen (HLA)-DRB1 alleles. However, in both studies, data analysis was not stratified by Löfgren's syndrome, a clinically and genetically distinct sarcoidosis subset. BTNL2, potentially encoding an immune coreceptor, is adjacent and in linkage disequilibrium (LD) with HLA-DRB1. We investigated six BTNL2 variants, including the functional rs2076530 (G > A), as well as HLA-DRB1 alleles, by sequence-specific primers-polymerase chain reaction, in 288 patients and 446 controls from two European countries. In the patient group as a whole, the HLA-DRB1*14 [odds ratio (OR) = 3.1, P(c) = 0.0003], DRB1*12 (OR = 2.5, P(c) = 0.003), and BTNL2 rs2076530 A allele (OR = 1.49, P(c) = 0.002) were all associated with disease susceptibility. However, after exclusion of patients presenting with Löfgren's syndrome and after adjusting for HLA-DRB1 alleles, the association between BTNL2 rs2076530 A and disease disappeared (P = 0.23). By contrast, both HLA-DRB1*14 and DRB1*12 remained strongly significant (OR = 3.60, P < 0.0001 and OR = 3.03, P = 0.003, respectively). BTNL2 haplotype 4, tagged by the rs2076530 G allele, also remained associated with non-Löfgren sarcoidosis after adjusting for HLA-DRB1 alleles (OR 0.37, P = 0.016). In summary, HLA-DRB1*14, DRB1*12, and BTNL2 haplotype 4--but not rs2076530 A--are associated with non-Löfgren sarcoidosis. However, the tight LD across the HLA complex makes it difficult to identify the precise location of the susceptibility locus/i. Larger sample sets from different ethnic groups, finer mapping, and more robust LD analyses across the HLA region are needed. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17661910&query_hl=1 ER - TY - JFULL T1 - Why do patients decline to take part in a research project involving pulmonary rehabilitation? A1 - Taylor, R A1 - Dawson, S A1 - Roberts, N A1 - Sridhar, M A1 - Partridge, MR J1 - Respir Med Y1 - 2007/09// VL - 101 SN - 0954-6111 SP - 1942 EP - 1946 N2 - BACKGROUND: It is important that those taking part in research trials are as representative as possible of those with the disease being studied. In a study of those with chronic obstructive pulmonary disease involving pulmonary rehabilitation, 120 of 297 suitable patients responded that they did not wish to take part in the trial. We were keen to know why these patients declined to take part in the study. METHODS: A total of 120 patients who had responded that they did not wish to take part in the main trial were approached to ask if they would be willing to undertake a semi-structured face-to-face interview in their own home or by telephone. Those who were willing (n=39) underwent tape-recorded interviews and data analysis was performed using the framework method. RESULTS: This was a qualitative study which revealed that several themes influenced patients' willingness or otherwise to take part in a research project involving pulmonary rehabilitation. Travelling to the hospital and location of the rehabilitation, along with competing commitments, and a variable perception of the benefits to the patient were clearly major factors and some had previous negative experiences of either the hospital, healthcare or research. While there was an element of negativity or impaired understanding regarding the research itself, the other factors appeared to be of greater importance. CONCLUSION: Recruitment to pulmonary rehabilitation courses or recruitment to research involving pulmonary rehabilitation may be more successful if the location of the rehabilitation can be made as near to the patient's home as possible, and if the patient is given as much information as possible about what is involved. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17540553&query_hl=1 ER - TY - JFULL T1 - Non-model-based correction of respiratory motion using beat-to-beat 3D spiral fat-selective imaging. A1 - Keegan, J A1 - Gatehouse, PD A1 - Yang, GZ A1 - Firmin, DN J1 - J Magn Reson Imaging Y1 - 2007/09// VL - 26 SN - 1053-1807 SP - 624 EP - 629 N2 - PURPOSE: To demonstrate the feasibility of retrospective beat-to-beat correction of respiratory motion, without the need for a respiratory motion model. MATERIALS AND METHODS: A high-resolution three-dimensional (3D) spiral black-blood scan of the right coronary artery (RCA) of six healthy volunteers was acquired over 160 cardiac cycles without respiratory gating. One spiral interleaf was acquired per cardiac cycle, prior to each of which a complete low-resolution fat-selective 3D spiral dataset was acquired. The respiratory motion (3D translation) on each cardiac cycle was determined by cross-correlating a region of interest (ROI) in the fat around the artery in the low-resolution datasets with that on a reference end-expiratory dataset. The measured translations were used to correct the raw data of the high-resolution spiral interleaves. RESULTS: Beat-to-beat correction provided consistently good results, with the image quality being better than that obtained with a fixed superior-inferior tracking factor of 0.6 and better than (N = 5) or equal to (N = 1) that achieved using a subject-specific retrospective 3D translation motion model. CONCLUSION: Non-model-based correction of respiratory motion using 3D spiral fat-selective imaging is feasible, and in this small group of volunteers produced better-quality images than a subject-specific retrospective 3D translation motion model. J. Magn. Reson. Imaging 2007;26:624-629. (c) 2007 Wiley-Liss, Inc. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17729350&query_hl=1 ER - TY - JFULL T1 - Elucidation of the temporal relationship between endothelial-derived NO and EDHF in mesenteric vessels. A1 - Harrington, LS A1 - Carrier, MJ A1 - Gallagher, N A1 - Gilroy, D A1 - Garland, CJ A1 - Mitchell, JA J1 - Am J Physiol Heart Circ Physiol Y1 - 2007/09// VL - 293 SN - 0363-6135 SP - H1682 EP - H1688 N2 - Although the endothelium co-generates both nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF), the relative contribution from each vasodilator is not clear. In studies where the endothelium is stimulated acutely, EDHF responses predominate in small arteries. However, the temporal relationship between endothelial-derived NO and EDHF over more prolonged periods is unclear but of major physiological importance. Here we have used a classical pharmacological approach to show that EDHF is released transiently compared with NO. Acetylcholine (3 x 10(-6) mol/l) dilated second- and/or third-order mesenteric arteries for prolonged periods of up to 1 h, an effect that was reversed fully and immediately by the subsequent addition of l-NAME (10(-3) mol/l) but not TRAM-34 (10(-6) mol/l) plus apamin (5 x 10(-7) mol/l). When vessels were pretreated with l-NAME, acetylcholine induced relatively transient dilator responses (declining over approximately 5 min), and vessels were sensitive to TRAM-34 plus apamin. When measured in parallel, the dilator effects of acetylcholine outlasted the smooth muscle hyperpolarization. However, in the presence of l-NAME, vasodilatation and hyperpolarization followed an identical time course. In vessels from NOSIII(-/-) mice, acetylcholine induced small but detectable dilator responses that were transient in duration and blocked by TRAM-34 plus apamin. EDHF responses in these mouse arteries were inhibited by an intracellular calcium blocker, TMB-8, and the phospholipase A(2) inhibitor AACOCF(3), suggesting a role for lipid metabolites. These data show for the first time that EDHF is released transiently, whereas endothelial-derived NO is released in a sustained manner. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17557917&query_hl=1 ER - TY - JFULL T1 - Combination treatment with omalizumab and rush immunotherapy for ragweed-induced allergic rhinitis: Inhibition of IgE-facilitated allergen binding. A1 - Klunker, S A1 - Saggar, LR A1 - Seyfert-Margolis, V A1 - Asare, AL A1 - Casale, TB A1 - Durham, SR A1 - Francis, JN A1 - the Immune Tolerance Network Group J1 - J Allergy Clin Immunol Y1 - 2007/09// VL - 120 SN - 0091-6749 SP - 688 EP - 695 N2 - BACKGROUND: The combination of anti-IgE (omalizumab) therapy with ragweed injection immunotherapy for seasonal allergic rhinitis results in a significant reduction in systemic side effects and enhanced efficacy compared with immunotherapy alone. One proposed mechanism of immunotherapy is to induce regulatory antibodies that inhibit facilitated antigen presentation. OBJECTIVES: We sought to determine whether the combination protocol has a cumulative effect on inhibition of facilitated antigen presentation both during and after discontinuation of treatment. METHODS: Ragweed allergen immunotherapy with and without omalizumab therapy was tested in a 4-arm, double-blind, placebo-controlled study. Flow cytometry was used to detect serum inhibitory activity for IgE-facilitated CD23-dependent allergen binding to B cells as a surrogate marker for facilitated antigen presentation. Serum ragweed-specific IgG4 was measured by means of ELISA. RESULTS: Immunotherapy alone resulted in partial inhibition of allergen-IgE binding after 5 to 19 weeks of treatment compared with baseline (P < .01). Complete inhibition of allergen-specific IgE binding was observed in both treatment groups receiving omalizumab (P < .001). Allergen-specific IgG4 levels were only increased after immunotherapy (P < .05), both in the presence and absence of anti-IgE treatment. Combined treatment resulted in the induction of long-lasting inhibitory antibody function for up to 42 weeks compared with either treatment alone. CONCLUSION: Ragweed immunotherapy induced serum regulatory antibodies that partially blocked binding of allergen-IgE complexes to B cells. Additional treatment with anti-IgE, by directly blocking IgE binding to CD23, completely inhibited allergen-IgE binding. CLINICAL IMPLICATIONS: The combination of ragweed immunotherapy and anti-IgE resulted in prolonged inhibition of allergen-IgE binding compared with either treatment alone, events that might contribute to enhanced efficacy. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17631952&query_hl=1 ER - TY - JFULL T1 - Novel role for the Liver X nuclear receptor in the suppression of lung inflammatory responses. A1 - Birrell, MA A1 - Catley, MC A1 - Hardaker, E A1 - Wong, S A1 - Willson, TM A1 - McCluskie, K A1 - Leonard, T A1 - Farrow, SN A1 - Collins, JL A1 - Haj-Yahia, S A1 - Belvisi, MG J1 - J Biol Chem Y1 - 2007/08/31/ SN - 0021-9258 N2 - The liver X receptors (LXRalpha/beta) are part of the nuclear receptor family and are believed to regulate cholesterol and lipid homeostasis. It has also been suggested that LXR agonists possess anti-inflammatory properties. The aim of this work was to determine the effect of LXR agonists on the innate immune response in human primary lung macrophages and a pre-clinical rodent model of lung inflammation. Prior to profiling the impact of the agonist we established that both the human macrophages and the rodent lungs expressed LXRalpha/beta. We then used two structurally distinct LXR agonists to demonstrate that activation of this transcription factor reduces cytokine production in THP-1 cells and lung macrophages. Then using the expression profile of ABCA-1 (a gene directly linked to LXR activation) as a biomarker for lung exposure of the compound, we demonstrated an LXR-dependent reduction in lung neutrophilia rodents in vivo. This inhibition was not associated with a suppression c-fos/c-jun mRNA expression or NF-kappaB/AP-1 DNA binding suggesting that any anti-inflammatory activity of LXR agonists is not via inhibition of NF-kappaB/AP-1 transcriptional activity. This data does not completely rule out an impact of these agonists on these two prominent transcription factors. In summary, this study is the first to demonstrate anti-inflammatory actions of LXRs in the lung. Chronic innate inflammatory responses observed in some airway diseases is thought to be central to disease pathogenesis. Therefore these data suggest that LXR ligands have utility in the treatment of lung diseases which involve chronic inflammation mediated by macrophages and neutrophils. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17766241&query_hl=1 ER - TY - JFULL T1 - Flow and myocardial interaction: an imaging perspective. A1 - Yang, GZ A1 - Merrifield, R A1 - Masood, S A1 - Kilner, PJ J1 - Philos Trans R Soc Lond B Biol Sci Y1 - 2007/08/29/ VL - 362 SN - 0962-8436 SP - 1329 EP - 1341 N2 - Heart failure due to coronary artery disease has considerable morbidity and poor prognosis. An understanding of the underlying mechanics governing myocardial contraction is a prerequisite for interpreting and predicting changes induced by heart disease. Gross changes in contractile behaviour of the myocardium are readily detected with existing techniques. For more subtle changes during early stages of cardiac dysfunction, however, a sensitive method for measuring, as well as a precise criterion for quantifying, normal and impaired myocardial function is required. The purpose of this paper is to outline the role of imaging, particularly cardiovascular magnetic resonance (CMR), for investigating the fundamental relationships between cardiac morphology, function and flow. CMR is emerging as an important clinical tool owing to its safety, versatility and the high-quality images it produces that allow accurate and reproducible quantification of cardiac structure and function. We demonstrate how morphological and functional assessment of the heart can be achieved by CMR and illustrate how blood flow imaging can be used to study flow and structure interaction, particularly for elucidating the underlying haemodynamic significance of directional changes and asymmetries of the cardiac looping. Future outlook on combining imaging with engineering approaches in subject-specific biomechanical simulation is also provided. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17584731&query_hl=1 ER - TY - JFULL T1 - Biological matrices and bionanotechnology. A1 - Taylor, PM J1 - Philos Trans R Soc Lond B Biol Sci Y1 - 2007/08/29/ VL - 362 SN - 0962-8436 SP - 1313 EP - 1320 N2 - A crucial step towards the goal of tissue engineering a heart valve will be the choice of scaffold onto which an appropriate cell phenotype can be seeded. Successful scaffold materials should be amenable to modification, have a controlled degradation, be compatible with the cells, lack cytotoxicity and not elicit an immune or inflammatory response. In addition, the scaffold should induce appropriate responses from the cells seeded onto it, such as cell attachment, proliferation and remodelling capacity, all of which should promote the formation of a tissue construct that can mimic the structure and function of the native valve. This paper discusses the various biological scaffolds that have been considered and are being studied for use in tissue engineering a heart valve. Also, strategies to enhance the biological communication between the scaffold and the cells seeded onto it as well as the use of bionanotechnology in the manufacture of scaffolds possessing the desired properties will be discussed. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17581810&query_hl=1 ER - TY - JFULL T1 - Immune response to stem cells and strategies to induce tolerance. A1 - Batten, P A1 - Rosenthal, NA A1 - Yacoub, MH J1 - Philos Trans R Soc Lond B Biol Sci Y1 - 2007/08/29/ VL - 362 SN - 0962-8436 SP - 1343 EP - 1356 N2 - Although recent progress in cardiovascular tissue engineering has generated great expectations for the exploitation of stem cells to restore cardiac form and function, the prospects of a common mass-produced cell resource for clinically viable engineered tissues and organs remain problematic. The refinement of stem cell culture protocols to increase induction of the cardiomyocyte phenotype and the assembly of transplantable vascularized tissue are areas of intense current research, but the problem of immune rejection of heterologous cell type poses perhaps the most significant hurdle to overcome. This article focuses on the potential advantages and problems encountered with various stem cell sources for reconstruction of the damaged or failing myocardium or heart valves and also discusses the need for integrating advances in developmental and stem cell biology, immunology and tissue engineering to achieve the full potential of cardiac tissue engineering. The ultimate goal is to produce 'off-the-shelf' cells and tissues capable of inducing specific immune tolerance. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17584730&query_hl=1 ER - TY - JFULL T1 - HDL-C in post-menopausal women: An important therapeutic target. A1 - Collins, P J1 - Int J Cardiol Y1 - 2007/08/29/ SN - 1874-1754 N2 - Coronary heart disease is a major cause of mortality in women in Western industrialised countries, particularly after the age of 50 years, coinciding with the onset of the menopause and potentially adverse metabolic changes that occur during the transitional peri-menopausal and post-menopausal periods. Dyslipidaemia characterised by increases in plasma levels of low-density lipoprotein cholesterol (LDL-C), triglycerides and lipoprotein(a) and a decrease in high-density lipoprotein cholesterol (HDL-C) together with the emergence of other diagnostic features of the metabolic syndrome are key factors that increase cardiovascular risk. Treatment beyond LDL-C with a combination of different lipid-modifying therapies may therefore be of greater importance in women than men. Fibrates and nicotinic acid are two treatments that may be added to primary statin therapy. Fibrates are more effective in lowering elevated triglycerides, whereas nicotinic acid is more effective in raising HDL-C. Although there is clearly a need for clinical trials in women, the available data suggests that combination lipid-modifying therapy is a logical treatment strategy in this high-risk patient group. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17764766&query_hl=1 ER - TY - JFULL T1 - Molecular and functional characteristics of heart-valve interstitial cells. A1 - Chester, AH A1 - Taylor, PM J1 - Philos Trans R Soc Lond B Biol Sci Y1 - 2007/08/29/ VL - 362 SN - 0962-8436 SP - 1437 EP - 1443 N2 - The cells that reside within valve cusps play an integral role in the durability and function of heart valves. There are principally two types of cells found in cusp tissue: the endothelial cells that cover the surface of the cusps and the interstitial cells (ICs) that form a network within the extracellular matrix (ECM) within the body of the cusp. Both cell types exhibit unique functions that are unlike those of other endothelial and ICs found throughout the body. The valve ICs express a complex pattern of cell-surface, cytoskeletal and muscle proteins. They are able to bind to, and communicate with, each other and the ECM. The endothelial cells on the outflow and inflow surfaces of the valve differ from one another. Their individual characteristics and functions reflect the fact that they are exposed to separate patterns of flow and pressure. In addition to providing a structural role in the valve, it is now known that the biological function of valve cells is important in maintaining the integrity of the cusps and the optimum function of the valve. In response to inappropriate stimuli, valve interstitial and endothelial cells may also participate in processes that lead to valve degeneration and calcification. Understanding the complex biology of valve interstitial and endothelial cells is an important requirement in elucidating the mechanisms that regulate valve function in health and disease, as well as setting a benchmark for the function of cells that may be used to tissue engineer a heart valve. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17569642&query_hl=1 ER - TY - JFULL T1 - Epigenetic regulation of airway inflammation. A1 - Adcock, IM A1 - Tsaprouni, L A1 - Bhavsar, P A1 - Ito, K J1 - Curr Opin Immunol Y1 - 2007/08/24/ SN - 0952-7915 N2 - Diverse cellular functions including the regulation of inflammatory gene expression, DNA repair and cell proliferation are regulated by epigenetic changes. Transcriptional co-activators possess intrinsic histone acetyltransferase (HAT) activity, and histone acetylation plays a major role in inflammatory gene expression. Other marks such as histone methylation are also associated with gene induction and gene repression. Recent evidence implicates histone acetylation and methylation as being crucial for the development of tolerance in macrophages and CpG methylation for T regulatory cell development and function. The expression of the enzymes that lay down or remove these epigenetic marks have not been well studied in human airways disease, but reduced HDAC2 expression and activity is reported in lung macrophages, biopsies and blood cells from patients with COPD, severe asthma and smoking asthma. In vitro, inhibitors of histone deacetylases (HDAC) often lead to a further induction of inflammatory gene expression. This is not always the case, however, as HATs and HDACs also target non-histone proteins particularly transcription factors to alter their activity. Furthermore, trichostatin A, an HDAC inhibitor, can reduce inflammation in a murine model of allergic asthma. This effect of HDAC inhibitors may be due to their effects on cell death acting through acetylation of non-histone proteins. The role of epigenetic modifications in inflammatory gene expression and in the control of cell function in the airways is becoming clearer. Targeting specific enzymes involved in this process may lead to new therapeutic agents, in particular, in situations where current anti-inflammatory therapies are currently suboptimal. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17720468&query_hl=1 ER - TY - JFULL T1 - Atrial enhancement by cardiovascular magnetic resonance in cardiac amyloidosis. A1 - Lyne, JC A1 - Petryka, J A1 - Pennell, DJ J1 - Eur Heart J Y1 - 2007/08/21/ SN - 0195-668X L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17704093&query_hl=1 ER - TY - JFULL T1 - Lung Delivery Studies Using siRNA Conjugated to TAT(48-60) and Penetratin Reveal Peptide Induced Reduction in Gene Expression and Induction of Innate Immunity. A1 - Moschos, SA A1 - Jones, SW A1 - Perry, MM A1 - Williams, AE A1 - Erjefalt, JS A1 - Turner, JJ A1 - Barnes, PJ A1 - Sproat, BS A1 - Gait, MJ A1 - Lindsay, MA J1 - Bioconjug Chem Y1 - 2007/08/21/ SN - 1043-1802 N2 - The therapeutic application of siRNA shows promise as an alternative approach to small-molecule inhibitors for the treatment of human disease. However, the major obstacle to its use has been the difficulty in delivering these large anionic molecules in vivo. In this study, we have investigated whether siRNA-mediated knockdown of p38 MAP kinase mRNA in mouse lung is influenced by conjugation to the nonviral delivery vector cholesterol and the cell penetrating peptides (CPP) TAT(48-60) and penetratin. Initial studies in the mouse fibroblast L929 cell line showed that siRNA conjugated to cholesterol, TAT(48-60), and penetratin, but not siRNA alone, achieved a limited reduction of p38 MAP kinase mRNA expression. Intratracheal administration of siRNA resulted in localization within macrophages and scattered epithelial cells and produced a 30-45% knockdown of p38 MAP kinase mRNA at 6 h. As with increasing doses of siRNA, conjugation to cholesterol improved upon the duration but not the magnitude of mRNA knockdown, while penetratin and TAT(48-60) had no effect. Importantly, administration of the penetratin or TAT(48-60) peptides alone caused significant reduction in p38 MAP kinase mRNA expression, while the penetratin-siRNA conjugate activated the innate immune response. Overall, these studies suggest that conjugation to cholesterol may extend but not increase siRNA-mediated p38 MAP kinase mRNA knockdown in the lung. Furthermore, the use of CPP may be limited due to as yet uncharacterized effects upon gene expression and a potential for immune activation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17711319&query_hl=1 ER - TY - JFULL T1 - An arm and a leg to protect the heart? A1 - Purcell, H A1 - Pepper, J J1 - Lancet Y1 - 2007/08/18/ VL - 370 SN - 1474-547X SP - 542 EP - 543 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17707732&query_hl=1 ER - TY - JFULL T1 - Suppression of lipopolysaccharide- and tumour necrosis factor-alpha-induced interleukin (IL)-8 expression by glucocorticoids involves changes in IL-8 promoter acetylation. A1 - Tsaprouni, LG A1 - Ito, K A1 - Adcock, IM A1 - Punchard, N J1 - Clin Exp Immunol Y1 - 2007/08/17/ SN - 0009-9104 N2 - There is accumulating evidence that the transrepressional effect of glucocorticoids in down-regulating proinflammatory gene expression might be regulated by an action on histone acetylation. To investigate this, we studied the effect of two glucocorticoids (dexamethasone and triamcinolone acetonide) on reducing lipopolysaccharide (LPS)- and tumour necrosis factor (TNF)-alpha-induced interleukin (IL)-8 release in a monocytic cell line and two lymphocytic cell lines (HUT-78 and Jurkat). The effect of the histone deacetylase inhibitor trichostatin A (TSA) on LPS- and TNF-alpha-induced IL-8 release and its repression by glucocorticoids was also examined. LPS and TNF-alpha induced IL-8 release in all three cell lines and this induction was inhibited by both dexamethasone and triamcinolone. Pretreatment of cells with TSA enhanced basal and LPS- and TNFalpha-stimulated IL-8 release in all three cell lines. TSA also attenuated the inhibitory effect of glucocorticoids on stimulated IL-8 release. Chromatin immunoprecipitation assays confirmed that LPS and TNF-alpha enhanced histone acetylation at the IL-8 promoter and that this was inhibited by triamcinolone in all three cell types. Changes in histone acetylation at the IL-8 are important in its regulation by proinflammatory and anti-inflammatory agents, and modulation of this activity may have therapeutic potential in inflammatory conditions. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17711487&query_hl=1 ER - TY - JFULL T1 - Early Detection of Airway Wall Remodelling and Eosinophilic Inflammation in Preschool Wheezers. A1 - Saglani, S A1 - Payne, DN A1 - Zhu, J A1 - Wang, Z A1 - Nicholson, AG A1 - Bush, A A1 - Jeffery, PK J1 - Am J Respir Crit Care Med Y1 - 2007/08/16/ SN - 1073-449X N2 - RATIONALE: It is unclear when the pathological features of asthma first appear. We hypothesised that eosinophilic airway inflammation and epithelial reticular basement membrane (RBM) thickening, absent in wheezy infants, would be present in preschool children with severe, recurrent wheeze. OBJECTIVES: To compare RBM thickness and inflammation in endobronchial biopsies (EB) from wheezy preschool children and age-matched controls. METHODS: EB were obtained from wheezy preschool children (aged 3 months to 5 years), undergoing a clinically indicated fibreoptic bronchoscopy (FOB). Subjects undergoing FOB to investigate stridor acted as non-asthma controls. RBM thickness was measured and the density of subepithelial, immunologically distinct inflammatory cells was determined and expressed as a volume fraction(%). EB from 16 children (median age 29 [7-57] months) with wheeze confirmed by video questionnaire (CW), 14 with reported wheeze (RW) (17 [8-58] months) and 10 controls (19 [5-42] months) were assessed. MEASUREMENTS AND MAIN RESULTS: RBM thickness in the three groups was: CW (median 4.6 [range 2.9-8.0]microm), RW (3.5 [2.1-5.4]microm), Controls (3.8 [2.5-4.7]microm). RBM was significantly thicker in CW than Controls, p<0.05. Eosinophil density was: CW (median 1.07 [range 0.0-3.52]%), RW (0.72 [0.0-2.04]%), Controls (0.0 [0.0-1.05]%). Eosinophilic inflammation was significantly greater in CW compared to Controls, p<0.05. There were no between-group differences for any other inflammatory cell phenotype. CONCLUSION: The characteristic pathological features of asthma in adults and school-aged children develop in preschool children with confirmed wheeze between the ages of one and three years, a time when intervention may modify the natural history of asthma. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17702968&query_hl=1 ER - TY - JFULL T1 - Pulmonary arterial thrombosis in eisenmenger syndrome is associated with biventricular dysfunction and decreased pulmonary flow velocity. A1 - Broberg, CS A1 - Ujita, M A1 - Prasad, S A1 - Li, W A1 - Rubens, M A1 - Bax, BE A1 - Davidson, SJ A1 - Bouzas, B A1 - Gibbs, JS A1 - Burman, J A1 - Gatzoulis, MA J1 - J Am Coll Cardiol Y1 - 2007/08/14/ VL - 50 SN - 1558-3597 SP - 634 EP - 642 N2 - OBJECTIVES: This study sought to determine what factors are associated with pulmonary artery thrombi in Eisenmenger patients. BACKGROUND: Pulmonary artery thrombosis is common in Eisenmenger syndrome, although its underlying pathophysiology is poorly understood. METHODS: Adult patients with Eisenmenger syndrome underwent computed tomography pulmonary angiography, cardiac magnetic resonance imaging, and echocardiography. Measurement of ventricular function, pulmonary artery size, and pulmonary artery blood flow were obtained. Hypercoagulability screening and platelet function assays were performed. RESULTS: Of 55 consecutive patients, 11 (20%) had a detectable thrombus. These patients were older (p = 0.032), but did not differ in oxygen saturation, hemoglobin, or hematocrit from those without thrombus. Right ventricular ejection fraction by magnetic resonance imaging was lower in those with thrombus (0.41 +/- 0.15 vs. 0.53 +/- 0.13, p = 0.017), as was left ventricular ejection fraction (0.48 +/- 0.12 vs. 0.60 +/- 0.09, p = 0.002), a finding corroborated by tissue Doppler and increased brain natriuretic peptide. Those with thrombus also had a larger main pulmonary artery diameter (48 +/- 14 mm vs. 38 +/- 9 mm, p = 0.007) and a lower peak systolic velocity in the pulmonary artery (p = 0.003). There were no differences in clotting factors, platelet function, or bronchial arteries between groups. Logistic regression showed pulmonary artery velocity to be independently associated with thrombosis. CONCLUSIONS: Pulmonary arterial thrombosis among adults with Eisenmenger syndrome is common and relates to older age, biventricular dysfunction, and slow pulmonary artery blood flow rather than degree of cyanosis or coagulation abnormalities. Further work to define treatment efficacy is needed. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17692749&query_hl=1 ER - TY - JFULL T1 - Perfusion CMR and SPECT in hypertrophic cardiomyopathy. A1 - O'hanlon, R A1 - Teo, K A1 - Bucciarelli-Ducci, C A1 - Pennell, DJ J1 - Int J Cardiol Y1 - 2007/08/14/ SN - 1874-1754 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17706805&query_hl=1 ER - TY - JFULL T1 - Anti-androgens increase N-terminal pro-BNP levels in men with prostate cancer. A1 - Dockery, F A1 - Bulpitt, CJ A1 - Agarwal, S A1 - Vernon, C A1 - Nihoyannopoulos, P A1 - Kemp, M A1 - Hooper, J A1 - Rajkumar, C J1 - Clin Endocrinol (Oxf) Y1 - 2007/08/13/ SN - 0300-0664 N2 - Objective The aim of this study was to determine the effects of anti-androgens on left ventricular (LV) function and levels of N-terminal proB-type natriuretic peptide (NT-proBNP), a sensitive cardiac risk marker, in men with prostate cancer as these are widely used drugs in this condition, and evidence suggests that endogenous androgens are cardioprotective in men. Design and patients Forty-three men (mean age 70.7 +/- 6.2 years) with prostate cancer were randomized to goserelin (an LH-releasing hormone analogue) or bicalutamide (an androgen-receptor blocker) for 6 months; 20 men with a history of prostate cancer on no treatment were studied in parallel. Results Mean changes in testosterone and oestradiol, respectively, from baseline to 6 months were -88% and -46% with goserelin, +50% and +44% with bicalutamide, and -1% and -9% for the 'no-treatment' group. Bicalutamide significantly increased NT-proBNP from baseline to 3 and 6 months (median value at baseline, 3 and 6 months: 55, 101 and 118 ng/l, respectively). Goserelin caused a significant increase from baseline to 3 months but not to 6 months (median value at baseline, 3 and 6 months: 66, 87 and 72 ng/l, respectively). No significant changes occurred in the 'no-treatment' cohort (median value at baseline 3 and 6 months: 60, 53 and 60 ng/l, respectively). No significant changes in LV function, blood pressure (BP), body mass index or waist-hip ratio occurred to account for the changes in NT-proBNP. Conclusion Androgen receptor blockade and, to a lesser extent, androgen suppression cause an increase in NT-pro-BNP in men with prostate cancer. The significance is not clear but could imply an adverse effect on cardiovascular risk following hormonal manipulation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17692108&query_hl=1 ER - TY - JFULL T1 - Is air travel safe for those with lung disease? A1 - Coker, RK A1 - Shiner, RJ A1 - Partridge, MR J1 - Eur Respir J Y1 - 2007/08/09/ SN - 0903-1936 N2 - Airlines commonly report respiratory in-flight emergencies; flight outcomes have not been examined prospectively in large numbers of respiratory patients. We conducted a prospective observational study of flight outcomes in this group.UK respiratory specialists were invited to recruit patients planning air travel. Centres undertook their usual pre-flight assessment. Within two weeks of return, patients completed a questionnaire documenting symptoms, in-flight oxygen use, and unscheduled healthcare use.Six hundred and sixteen patients were recruited; 500 (81%) returned questionnaires. The commonest diagnoses were airway (54%) and diffuse parenchymal lung disease (23%). Twelve patients died, seven before flying and five within one month. Pre-flight assessment included oximetry (96%), spirometry (95%), hypoxic challenge (45%) and walk test (10%). Eleven percent did not fly. In those who flew, unscheduled respiratory healthcare use rose from 9% in the four weeks beforehand to 19% in the four weeks after travel. However, when compared with self-reported data during the preceding year, medical consultations rose by just 2%.In patients flying after careful respiratory specialist assessment, commercial air travel appears generally safe. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17690127&query_hl=1 ER - TY - JFULL T1 - Comorbidity, health care utilisation and process of care measures in patients with congenital heart disease in the UK: cross-sectional population-based study with case control analysis. A1 - Billett, J A1 - Cowie, MR A1 - Gatzoulis, MA A1 - Vonder Muhll, IF A1 - Majeed, A J1 - Heart Y1 - 2007/08/07/ SN - 1468-201X N2 - Background Relatively little is known about the prevalence of comorbidities, patterns of health care utilisation and primary care recording of clinical indicators in patients with congenital heart disease. Methods We conducted a population-based case control study using data from general practices across the UK contributing data to the QRESEARCH primary care database. The subjects were 9952 cases of congenital heart disease and 29837 matched controls. Outcome measures were: Prevalence (%) of selected comorbidities; adjusted odds ratios (OR) for risk of comorbidities, health care utilisation and clinical indicator recording. Results The overall crude prevalence of congenital heart disease was 3.05 per 1000 patients (95% CI 2.90 to 3.11). Prevalence of key comorbidities in congenital heart disease patients ranged from 2.4% (95% CI 2.1 to 2.7) for epilepsy to 9.3% (95% CI 8.8 to 9.9) for hypertension. After adjusting for smoking and deprivation, cases were significantly more likely than controls to have each of the cardiovascular comorbidities e.g. adjusted odds ratio for atrial fibrillation 7.6 (6.1 to 9.3), and also had an increased risk of diabetes, epilepsy and renal disease. Patients with congenital heart disease were heavier users of primary care than controls. congenital heart disease patients were also more likely than controls to have lifestyle and risk factor measurements recorded in primary care e.g. adjusted odds ratio for BMI recording in cases versus controls 1.23 (95% CI 1.16 to 1.31), although overall levels of recording were low. Conclusions There is a significant burden of comorbidity associated with congenital heart disease, and levels of primary care utilisation and referral to secondary care are high in this patient population. The predicted future expansion in the numbers of adults with congenital heart disease owing to improvements in survival will have implications for primary and secondary care, and not just tertiary centres offering specialist care. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17646191&query_hl=1 ER - TY - JFULL T1 - Images in cardiovascular medicine. Myocarditis and sudden cardiac death in the young: extensive fibrosis suggested by cardiovascular magnetic resonance in vivo and confirmed post mortem. A1 - Babu-Narayan, SV A1 - McCarthy, KP A1 - Ho, SY A1 - Magee, AG A1 - Kilner, PJ A1 - Sheppard, MN J1 - Circulation Y1 - 2007/08/07/ VL - 116 SN - 1524-4539 SP - e122 EP - e125 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17679621&query_hl=1 ER - TY - JFULL T1 - Endothelial-dependent mechanisms of leukocyte recruitment to the vascular wall. A1 - Rao, RM A1 - Yang, L A1 - Garcia-Cardena, G A1 - Luscinskas, FW J1 - Circ Res Y1 - 2007/08/03/ VL - 101 SN - 1524-4571 SP - 234 EP - 247 N2 - Inflammation is a fundamental process that protects organisms by removing or neutralizing injurious agents. A key event in the inflammatory response is the localized recruitment of various leukocyte subsets. Here we address the cellular and regulatory mechanisms of leukocyte recruitment to the vessel wall in cardiovascular disease and discuss our evolving understanding of the role of the vascular endothelium in this process. The vascular endothelium is the continuous single-cell lining of the cardiovascular system that forms a critical interface between the blood and its components on one side and the tissues and organs on the other. It is heterogeneous and has many synthetic and metabolic functions including secretion of platelet-derived growth factor, von Willebrand factor, prostacyclin, NO, endothelin-1, and chemokines and the expression of adhesion molecules. It also acts as a nonthrombogenic and selective permeable barrier. Endothelial cells also interact closely with the extracellular matrix and with adjacent cells including pericytes and smooth muscle cells within the vessel wall. A central question in vascular biology is the role of the endothelium in the initiation of inflammatory response, the extent of its "molecular conversations" with recruited leukocytes, and its influence on the extent and/or outcome of this response. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17673684&query_hl=1 ER - TY - JFULL T1 - Long-term safety, tolerability and efficacy of bosentan in adults with pulmonary arterial hypertension associated with congenital heart disease. A1 - Diller, GP A1 - Dimopoulos, K A1 - Kaya, MG A1 - Harries, C A1 - Uebing, A A1 - Li, W A1 - Koltsida, E A1 - Gibbs, JS A1 - Gatzoulis, MA J1 - Heart Y1 - 2007/08// VL - 93 SN - 1468-201X SP - 974 EP - 976 N2 - OBJECTIVE: To examine long-term safety and efficacy of bosentan--an oral dual endothelin receptor antagonist--in patients with pulmonary hypertension associated with congenital heart disease or Eisenmenger's syndrome. DESIGN: Retrospective study. SETTING: Tertiary cardiology referral centre. PATIENTS: All adult patients with pulmonary arterial hypertension associated with congenital heart disease treated with bosentan at the Royal Brompton Adult Congenital Heart Centre were included. MAIN OUTCOME MEASURES: Oxygen saturation, functional (WHO) class, 6-minute walk test distance and liver enzymes were analysed. RESULTS: Eighteen patients (14 female) with pulmonary arterial hypertension associated with congenital heart disease (15 patients with Eisenmenger's syndrome) with a mean (SD) age of 41 (9) years (range 23-69) were included. Median follow-up was 29 months (range 1-39). One patient died during follow-up. Patients tolerated bosentan well and no significant rise in liver transaminases was seen. Arterial oxygen saturation remained stable throughout follow-up. Mean (SD) functional class (p = 0.001) and the 6-minute walk test distance improved compared with baseline (284 (144) vs 363 (124) m, 380 (91) m and 408 (114) m at baseline, 0-6 months, 6-12 months and 1-2 years of treatment, respectively; p<0.05 for each). CONCLUSIONS: Bosentan appears to be safe and well tolerated in adults with pulmonary arterial hypertension associated with congenital heart disease or Eisenmenger's syndrome during mid- to long-term follow-up. In addition, functional class and the 6-minute walk test distance improved and this effect was maintained for up to 2 years of bosentan treatment. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17639112&query_hl=1 ER - TY - JFULL T1 - Uric acid and other renal function parameters in patients with stable angina pectoris participating in the ACTION trial: impact of nifedipine GITS (gastro-intestinal therapeutic system) and relation to outcome. A1 - Ruilope, LM A1 - Kirwan, BA A1 - de Brouwer, S A1 - Danchin, N A1 - Fox, KA A1 - Wagener, G A1 - Segura, J A1 - Poole-Wilson, PA A1 - Lubsen, J A1 - on behalf of the ACTION investigators J1 - J Hypertens Y1 - 2007/08// VL - 25 SN - 0263-6352 SP - 1711 EP - 1718 N2 - BACKGROUND: Little data is available concerning the prognostic implications of renal function abnormalities, their evolution over time and the effects of nifedipine on such abnormalities in patients with stable angina pectoris. METHODS: The previously published ACTION trial compared long-acting nifedipine GITS 60 mg once daily to placebo among 7,665 patients. Standard laboratory tests including creatinine and uric acid were assessed at baseline, after 6 months, 2 and 4 years, and at the end of follow-up. We assessed the impact of nifedipine on markers of renal dysfunction and determined whether evidence of renal failure alters the impact of nifedipine on the clinical outcome of patients with stable angina. RESULTS: Uric acid was not while creatinine level and estimated creatinine clearance were potent conditionally independent predictors of total mortality and of cardiovascular clinical events. Relative to placebo, nifedipine reduced 6-month uric acid levels by 3% (P < 0.001) of the baseline value. This difference was maintained during long-term follow-up, was present both in normotensives and in hypertensives, and was not explained by differences in diuretic therapy or allopurinol use. Nifedipine had no effect on the occurrence of clinical renal failure. Relative to placebo, the effects of nifedipine on cardiovascular death or myocardial infarction [hazard ratio (HR) = 1.01, 95% confidence interval (CI) 0.88-1.17], any stroke or transient ischaemic attack (HR = 0.73, 95% CI 0.60-0.88), new overt heart failure (HR = 0.72, 95% CI 0.55-0.95), and the need for any coronary procedure (HR = 0.81, 95% CI 0.75-0.88) were consistent across strata of markers of renal dysfunction. CONCLUSIONS: We conclude that, in patients with stable angina, nifedipine reduces uric acid levels and does not affect other markers of renal dysfunction. Renal dysfunction does not alter the effects of nifedipine on clinical outcome. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17620970&query_hl=1 ER - TY - JFULL T1 - The association of left ventricular mass with blood pressure, cigarette smoking and alcohol consumption; data from the LARGE heart study A1 - Payne, JR A1 - James, LE A1 - Eleftheriou, KI A1 - Hawe, E A1 - Mann, J A1 - Stronge, A A1 - Banham, K A1 - World, M A1 - Humphries, SE A1 - Pennell, DJ A1 - Montgomery, HE J1 - INT J CARDIOL Y1 - 2007/08// VL - 120 SN - 0167-5273 SP - 52 EP - 58 N2 - Background: Left ventricular mass is a risk factor for cardiovascular morbidity and mortality. Although factors associated with elevated left ventricular mass have been sought and studied extensively in elderly and in diseased subjects, few studies have examined the young and healthy. The aim of this study was to examine the possible influence of lifestyle on left ventricular mass in a large group of young men.Methods: Left ventricular mass was assessed using cardiovascular magnetic resonance in 541 healthy Caucasian male army recruits. Anthropometric, lifestyle and blood pressure data were collected.Results: Mean unadjusted left ventricular mass and left ventricular mass indexed to body surface area were 163.8 +/- 24.9 g and 86.6 +/- 10.2 g m-2 respectively. In univariate analysis, age, height, weight, alcohol consumption, systolic blood pressure, diastolic blood pressure and indices of physical activity were positively associated with unadjusted left ventricular mass (all P < 0.02). By contrast, smoking was associated with lower mean left ventricular mass; never smoked 167.5 +/- 25.8 g vs ex-smokers 159.1 +/- 25.2 g vs current smokers 161.0 +/- 23.1 g (P= 0.007). Multivariate analysis revealed weight, systolic blood pressure, smoking status and indices of physical activity to be independent predictors of left ventricular mass.Conclusions: Our data confirm an association of age, body weight, height, physical activity, diastolic and systolic blood pressure with left ventricular mass. In addition, unexpectedly, we have found smoking is associated with lower left ventricular mass in a large sample of young healthy men. Although the latter association may result from confounding effects, such an interesting observation deserves further investigation. (C) 2006 Elsevier Ireland Ltd. All rights reserved. ER - TY - JFULL T1 - Grass allergen tablet immunotherapy relieves individual seasonal eye and nasal symptoms, including nasal blockage. A1 - Durham, SR A1 - Riis, B J1 - Allergy Y1 - 2007/08// VL - 62 SN - 0105-4538 SP - 954 EP - 957 N2 - BACKGROUND: Symptoms of allergic rhinitis have a considerable impact on the quality of life of the sufferer. Sneezing, runny nose, blocked nose and headache are some of the most common symptoms of allergic rhinitis, which affects work, home and social life for many patients. Sublingual immunotherapy has shown to induce a protective immune response and provide sustained symptom prevention for allergic patients. AIMS OF THE TRIAL: The overall aims were to investigate the efficacy and safety of a sublingual grass allergen tablet (Grazax) 75 000 SQ-T; ALK-Abelló A/S, Denmark). Reported here are the effects of Grazax on individual eye and nasal symptoms. METHODS: The trial was a double-blind placebo-controlled trial including 634 participants with significant rhinoconjunctivitis because of grass pollen. Participants were randomized 1 : 1 to Grazax (a fast dissolving, once daily immunotherapy tablet for home administration) or placebo and received treatment for at least 16 weeks prior to and continuing during the grass pollen season of 2005. Four nasal symptoms and two eye symptoms were scored on a scale from 0 (no symptoms) to 3 (severe symptoms) every day during the entire grass pollen season. Nasal symptoms included runny nose, blocked nose, sneezing and itchy nose; eye symptoms included gritty feeling/red/itchy eyes and watery eyes. RESULTS: Consistent and highly significant reductions in individual eye and nasal symptoms (from 22 to 44%) were observed following treatment with Grazax as compared with placebo (P < 0.0001). CONCLUSIONS: Grazax has effects on multiple allergic symptoms, including nasal blockage, and is an effective treatment of rhinoconjunctivitis, thereby reducing the need for topical anti-allergic drugs. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17620075&query_hl=1 ER - TY - JFULL T1 - Management of cardiovascular risk in the peri-menopausal woman: a consensus statement of European cardiologists and gynaecologists. A1 - Collins, P A1 - Rosano, G A1 - Casey, C A1 - Daly, C A1 - Gambacciani, M A1 - Hadji, P A1 - Kaaja, R A1 - Mikkola, T A1 - Palacios, S A1 - Preston, R A1 - Simon, T A1 - Stevenson, J A1 - Stramba-Badiale, M J1 - Eur Heart J Y1 - 2007/08// VL - 28 SN - 0195-668X SP - 2028 EP - 2040 N2 - Cardiovascular risk is poorly managed in women, especially during the menopausal transition when susceptibility to cardiovascular events increases. Clear gender differences exist in the epidemiology, symptoms, diagnosis, progression, prognosis, and management of cardiovascular risk. Key risk factors that need to be controlled in the peri-menopausal woman are hypertension, dyslipidaemia, obesity, and other components of the metabolic syndrome, with the avoidance and careful control of diabetes. Hypertension is a particularly powerful risk factor and lowering of blood pressure is pivotal. Hormone replacement therapy is acknowledged as the gold standard for the alleviation of the distressing vasomotor symptoms of the menopause, but the findings of the Women's Health Initiative (WHI) study generated concern for the detrimental effect on cardiovascular events. Thus, hormone replacement therapy cannot be recommended for the prevention of cardiovascular disease. Whether the findings of WHI in older post-menopausal women can be applied to younger peri-menopausal women is unknown. It is increasingly recognized that hormone therapy is inappropriate for older post-menopausal women no longer displaying menopausal symptoms. Both gynaecologists and cardiovascular physicians have an important role to play in identifying peri-menopausal women at risk of cardiovascular morbidity and mortality and should work as a team to identify and manage risk factors such as hypertension. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17644507&query_hl=1 ER - TY - JFULL T1 - Effect of an inducible nitric oxide synthase inhibitor on differential flow-exhaled nitric oxide in asthmatic patients and healthy volunteers. A1 - Brindicci, C A1 - Ito, K A1 - Barnes, PJ A1 - Kharitonov, SA J1 - Chest Y1 - 2007/08// VL - 132 SN - 0012-3692 SP - 581 EP - 588 N2 - Nitric oxide (NO) is produced by a variety of cells within the respiratory tract, particularly airway epithelial cells, and its increased concentration in asthma is likely to derive from inducible NO synthase (iNOS) expressed in inflamed airways. To evaluate whether an increased bronchial flux of NO (ie, airway wall NO flux [Jno] in picoliters per second) produced in the large airways is due to an enzyme overexpression, we administered a relatively selective iNOS inhibitor, aminoguanidine, by nebulization in a double-blind, placebo-controlled manner in asthmatic and healthy subjects and also investigated whether the same concentration of inhibitor has any effect on NO produced in the peripheral lungs (ie, alveolar NO concentration [Calv] in parts per billion [ppb]) or on the diffusing capacity of NO (Dno) [in picoliters per second(-1) per ppb(-1)) in the airways. Aminoguanidine administration resulted in a significant reduction in Jno compared with administration of the saline solution control in eight healthy subjects and in eight patients with asthma but caused no significant changes in Calv or in Dno in either group. No rise in BP, fall in FEV(1), or adverse effects were observed in either group. These results indicate that iNOS from larger airways is the predominant source of elevated large airway-derived NO in patients with asthma, and that exhaled NO from peripheral lungs is not affected by a nebulized iNOS inhibitor and, therefore, is more likely to be derived form constitutive forms of NO synthase. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17550932&query_hl=1 ER - TY - JFULL T1 - Cardiovascular magnetic resonance in the evaluation of heart failure. A1 - Assomull, RG A1 - Pennell, DJ A1 - Prasad, SK J1 - Heart Y1 - 2007/08// VL - 93 SN - 1468-201X SP - 985 EP - 992 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17639116&query_hl=1 ER - TY - JFULL T1 - In vivo evidence for apoptosis in the bone marrow in systemic lupus erythematosus. A1 - Hepburn, AL A1 - Lampert, IA A1 - Boyle, JJ A1 - Horncastle, D A1 - Ng, WF A1 - Layton, M A1 - Vyse, TJ A1 - Botto, M A1 - Mason, JC J1 - Ann Rheum Dis Y1 - 2007/08// VL - 66 SN - 0003-4967 SP - 1106 EP - 1109 N2 - An increase in leucocyte apoptosis and impaired clearance of apoptotic cells has been observed in patients with systemic lupus erythematosus (SLE). Apoptotic cells are likely to be a key source of autoantigens in SLE as they express many of the nuclear autoantigens (in surface blebs and apoptotic bodies) that are relevant to this disease. The clearance of apoptotic cells is usually a rapid process, such that few cells are usually seen in the extracellular environment in vivo. We report a case in which multiple apoptotic bodies were observed in the bone marrow of a patient with SLE that was complicated by an immune-mediated pancytopenia. We have subsequently examined the frequency of apoptotic cells, identified morphologically, and by caspase-3 staining in bone-marrow trephine samples taken from patients with SLE over a 10-year period of follow-up. A high proportion of bone marrows contained apoptotic debris. The novel demonstration of apoptotic bodies in vivo in patients with SLE is unusual and supports the notion that the marrow may be a target organ in the disease. Their abundance is also consistent with the hypothesis that normal clearance mechanisms are defective and/or overwhelmed in SLE. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17277002&query_hl=1 ER - TY - JFULL T1 - Telephone consultations in secondary care. A1 - Roberts, NJ A1 - Partridge, MR J1 - Respir Med Y1 - 2007/08// VL - 101 SN - 0954-6111 SP - 1665 EP - 1669 N2 - OBJECTIVE: To determine the role of telephone consultations in respiratory medicine. DESIGN: An observational study. SETTING: Respiratory outpatients department in an inner London teaching hospital. PARTICIPANTS: Five-hundred sequential patients attending three different outpatient respiratory clinics. INTERVENTION: Substitution of the next intended consultation with a telephone consultation. OUTCOME MEASURES: Proportion of patients suitable for telephone consultation, their availability when telephoned, length of consultation and patient satisfaction. CONCLUSIONS: Telephone consultations are an effective alternative to traditional consultations in a third of respiratory patients attending for hospital follow-up. This style of consultation allows the option of not attending the hospital for a consultation and 23.9% had their consultation at their place of work. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17448649&query_hl=1 ER - TY - JFULL T1 - Arterial carboxyhemoglobin level and outcome in critically ill patients. A1 - Melley, DD A1 - Finney, SJ A1 - Elia, A A1 - Lagan, AL A1 - Quinlan, GJ A1 - Evans, TW J1 - Crit Care Med Y1 - 2007/08// VL - 35 SN - 0090-3493 SP - 1882 EP - 1887 N2 - OBJECTIVE:: Arterial carboxyhemoglobin is elevated in patients with critical illness. It is an indicator of the endogenous production of carbon monoxide by the enzyme heme oxygenase, which modulates the response to oxidant stress. The objective was to explore the hypothesis that arterial carboxyhemoglobin level is associated with inflammation and survival in patients requiring cardiothoracic intensive care. DESIGN:: Prospective, observational study. SETTING:: A cardiothoracic intensive care unit. PATIENTS:: All patients admitted over a 15-month period. INTERVENTIONS:: None. MEASUREMENTS AND MAIN RESULTS:: Arterial carboxyhemoglobin, bilirubin, and standard biochemical, hematologic, and physiologic markers of inflammation were measured in 1,267 patients. Associations were sought between levels of arterial carboxyhemoglobin, markers of the inflammatory response, and clinical outcome. Intensive care unit mortality was associated with lower minimum and greater maximal carboxyhemoglobin levels (p < .0001 and p < .001, respectively). After adjustment for age, gender, illness severity, and other relevant variables, a lower minimum arterial carboxyhemoglobin was associated with an increased risk of death from all causes (odds risk of death, 0.391; 95% confidence interval, 0.190-0.807; p = .011). Arterial carboxyhemoglobin correlated with markers of the inflammatory response. CONCLUSIONS:: Both low minimum and high maximum levels of arterial carboxyhemoglobin were associated with increased intensive care mortality. Although the heme oxygenase system is protective, excessive induction may be deleterious. This suggests that there may be an optimal range for heme oxygenase-1 induction. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17568332&query_hl=1 ER - TY - JFULL T1 - Clinical course of isolated stable angina due to coronary heart disease. A1 - Poole-Wilson, PA A1 - Vokó, Z A1 - Kirwan, BA A1 - de Brouwer, S A1 - Dunselman, PH A1 - Lubsen, J A1 - for the ACTION investigators J1 - Eur Heart J Y1 - 2007/08// VL - 28 SN - 0195-668X SP - 1928 EP - 1935 N2 - Aims To describe the clinical course of patients with stable angina due to coronary heart disease without a history of cardiovascular (CV) events or revascularization (isolated angina). Methods and results Of 7665 patients in a trial comparing long-acting nifedipine with placebo, 2170 (28%) had isolated angina. During a mean follow-up of 4.9 years, 147 of these died (1.4/100 patient-years), while 761 (8.7/100 patient-years) either died, or had a cardiac event or procedure. The first event was death in 82, myocardial infarction or heart failure in 112, coronary revascularization in 171, and chest pain requiring hospitalization in 396. Six hundred and twelve patients (6.8/100 patient-years) underwent coronary angiography (CAG), followed by revascularization in 371. Sixty-eight of 262 deaths or major cardiac events were preceded by chest pain requiring hospitalization or revascularization. Event-rates after CAG were higher than before. The stroke rate was 0.7/100 patient-years (75 patients). Conclusion Patients with stable isolated angina have low rates of death and major cardiac events, but relatively high rates of chest pain requiring hospitalization despite contemporary management. Since the majority of deaths and major CV clinical events are not preceded by clear warning symptoms, the main clinical implication is that measures to prevent such events must target all patients. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17562665&query_hl=1 ER - TY - JFULL T1 - The challenge of asthma in adolescence. A1 - de Benedictis, D A1 - Bush, A J1 - Pediatr Pulmonol Y1 - 2007/08// VL - 42 SN - 8755-6863 SP - 683 EP - 692 N2 - The adolescents with asthma are a distinct group of patients with different problems and needs compared to children and adults. Specific issues of asthma in adolescence are the variability of the clinical spectrum, the presence of particular risk factors for the persistence of symptoms, underdiagnosis and undertreatment of the disease. Refusal of the sick role, denial of symptoms, carelessness about dangerous inhalation exposure, erratic self-medication, overexertion without taking precautions against exercise-induced asthma, and a poor relationship between patients, their families, and often doctors are the main obstacles to successful management of asthma in this critical age. There are also major problems of compliance for these patients. The goal of optimal quality of life will be achieved only if the physician thoroughly understands the adolescent's needs and provides optimal care. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17595039&query_hl=1 ER - TY - JFULL T1 - Predictive value of local and core laboratory echocardiographic assessment of cardiac function in patients with chronic stable angina: The ACTION study. A1 - Dart, AM A1 - Otterstad, JE A1 - Kirwan, BA A1 - Parker, JD A1 - de Brouwer, S A1 - Poole-Wilson, PA A1 - Lubsen, J A1 - ACTION investigators J1 - Eur J Echocardiogr Y1 - 2007/08// VL - 8 SN - 1525-2167 SP - 275 EP - 283 N2 - AIMS: To evaluate the relationship between echocardiographic cardiac function and outcome in patients with stable symptomatic angina. METHODS: Baseline echo left ventricular ejection fraction and volume data measured in a central laboratory was available for 7016 patients (92% of the total) participating in the ACTION trial (A Coronary disease Trial Investigating Outcome with Nifedipine GITS). Ejection fraction was also measured by investigators. Evaluation of the different echocardiographic variables was based on adjusted hazard ratios comparing the unfavourable limit of the 90% range of the variable concerned to the favourable limit. RESULTS: The centrally measured ejection fraction was the most powerful predictor of all-cause death (adjusted hazard ratio=2.5), myocardial infarction, any stroke or transient ischaemic attack and overt heart failure (adjusted hazard ratio=4.5). The addition of either end systolic volume or end diastolic volume to ejection fraction did not materially affect the power of prediction. Compared to the central ejection fraction measurement, the investigator-measured ejection fraction was a less powerful predictor for all outcomes considered. CONCLUSION: Routine echocardiography carefully analysed by standardised methods provides useful prognostic information in patients with stable angina, including for total mortality. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17416207&query_hl=1 ER - TY - JFULL T1 - Protective effect of fruits, vegetables and the Mediterranean diet on asthma and allergies among children in Crete. A1 - Chatzi, L A1 - Apostolaki, G A1 - Bibakis, I A1 - Skypala, I A1 - Bibaki-Liakou, V A1 - Tzanakis, N A1 - Kogevinas, M A1 - Cullinan, P J1 - Thorax Y1 - 2007/08// VL - 62 SN - 0040-6376 SP - 677 EP - 683 N2 - BACKGROUND: Atopy is not uncommon among children living in rural Crete, but wheeze and rhinitis are rare. A study was undertaken to examine whether this discrepancy could be attributed to a high consumption of fresh fruit and vegetables or adherence to a traditional Mediterranean diet. METHODS: A cross-sectional survey was performed in 690 children aged 7-18 years in rural Crete. Parents completed a questionnaire on their child's respiratory and allergic symptoms and a 58-item food frequency questionnaire. Adherence to a Mediterranean diet was measured using a scale with 12 dietary items. Children underwent skin prick tests with 10 common aeroallergens. RESULTS: 80% of children ate fresh fruit (and 68% vegetables) at least twice a day. The intake of grapes, oranges, apples, and fresh tomatoes-the main local products in Crete-had no association with atopy but was protective for wheezing and rhinitis. A high consumption of nuts was found to be inversely associated with wheezing (OR 0.46; 95% CI 0.20 to 0.98), whereas margarine increased the risk of both wheeze (OR 2.19; 95% CI 1.01 to 4.82) and allergic rhinitis (OR 2.10; 95% CI 1.31 to 3.37). A high level of adherence to the Mediterranean diet was protective for allergic rhinitis (OR 0.34; 95% CI 0.18 to 0.64) while a more modest protection was observed for wheezing and atopy. CONCLUSION: The results of this study suggest a beneficial effect of commonly consumed fruits, vegetables and nuts, and of a high adherence to a traditional Mediterranean diet during childhood on symptoms of asthma and rhinitis. Diet may explain the relative lack of allergic symptoms in this population. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17412780&query_hl=1 ER - TY - JFULL T1 - Signaling pathways mediating cardiac myocyte gene expression in physiological and stress responses. A1 - Clerk, A A1 - Cullingford, TE A1 - Fuller, SJ A1 - Giraldo, A A1 - Markou, T A1 - Pikkarainen, S A1 - Sugden, PH J1 - J Cell Physiol Y1 - 2007/08// VL - 212 SN - 0021-9541 SP - 311 EP - 322 N2 - The contractile cells in the heart (the cardiac myocytes) are terminally differentiated. In response to pathophysiological stresses, cardiac myocytes undergo hypertrophic growth or apoptosis, responses associated with the development of cardiac pathologies. There has been much effort expended in gaining an understanding of the stimuli which promote these responses, and in identifying the intracellular signaling pathways which are activated and potentially involved. These signaling pathways presumably modulate gene and protein expression to elicit the end-stage response. For the regulation of gene expression, the signal may traverse the cytoplasm to modulate nuclear-localized transcription factors as occurs with the mitogen-activated protein kinase or protein kinase B/Akt cascades. Alternatively, the signal may promote translocation of transcription factors from the cytoplasm to the nucleus as is seen with the calcineurin/NFAT and JAK/STAT systems. We present an overview of the principal signaling pathways implicated in the regulation of gene expression in cardiac myocyte pathophysiology, and summarize the current understanding of these pathways, the transcription factors they regulate and the changes in gene expression associated with the development of cardiac pathologies. Finally, we discuss how intracellular signaling and gene expression may be integrated to elicit the overall change in cellular phenotype. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17450511&query_hl=1 ER - TY - JFULL T1 - Use of albumin creatinine ratio and urine albumin concentration as a screening test for albuminuria in an Indo-Asian population. A1 - Jafar, TH A1 - Chaturvedi, N A1 - Hatcher, J A1 - Levey, AS J1 - Nephrol Dial Transplant Y1 - 2007/08// VL - 22 SN - 0931-0509 SP - 2194 EP - 2200 N2 - BACKGROUND: Albuminuria (>30 mg/day) based on 24 h urine albumin excretion is one of the criteria for chronic kidney disease (CKD) and a predictor of cardiovascular disease (CVD). Differences in urine albumin concentration and creatinine excretion rates between Indo-Asians and other populations may require different threshold values for detection of albuminuria. We compared the use of spot urine albumin concentration and urine albumin to creatinine excretion ratio for detection of albuminuria in this population. METHODS: A total of 577 subjects aged >/=40 years, 54% of whom were women, were recruited from the general population in Karachi, Pakistan. Albumin concentration (mg/l) and albumin to creatinine ratio (mg/g of creatinine) were determined in a spot morning urine sample, and albuminuria (30 mg/day or greater) measured in a 24 h urine collected on the subsequent day. RESULTS: The median (25-75 percentile) of urine albumin excretion was 4.8 (3.6-10.3) mg/day: 5.4 (3.7-12.5) mg/day in men and 4.5 (3.8-8.9) mg/day in women. The overall prevalence (95% CI) of albuminuria was 11.8% (7.2-12.0%): 14.8% in men and 9.2% in women (P = 0.04). The areas under the receiver operator characteristic (ROC) curves for urine albumin concentration were 0.86 (0.82-0.90) and 0.88 (0.84-0.92), respectively, in women and men. The areas under the ROC curves for albumin to creatinine ratio were 0.86 (0.82-0.89) and 0.90 (0.86-0.93), respectively, in women and men. For urine albumin concentration, the sensitivity and specificity were 37 and 97%, respectively, in women and 69 and 94%, respectively, in men at the conventionally recommended value of 2 mg/dl. The discriminator value of urine albumin concentration identified in the analysis was 0.5 mg/dl in women (sensitivity of 87% and specificity of 75%) and 1.7 mg/dl in men (sensitivity of 74% and specificity of 93%). For the albumin to creatinine ratio, the sensitivity and specificity were 46 and 95%, respectively, in women and 60 and 97%, respectively, in men at cut-off value of 30 mg/g. CONCLUSION: Both urine albumin concentration and albumin to creatinine ratio are acceptable tests for population screening for albuminuria in Indo-Asians. While sensitivities may be suboptimal, particularly in women, lowering the existing thresholds would compromise specificity. Those who screen positive need evaluation and management of CKD and prevention of CVD. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17405790&query_hl=1 ER - TY - JFULL T1 - Reproducibility of cardioventilatory measurements using a respiratory mass spectrometer. A1 - Narang, I A1 - Rosenthal, M A1 - Bush, A J1 - Respir Physiol Neurobiol Y1 - 2007/08/01/ VL - 157 SN - 1569-9048 SP - 310 EP - 315 N2 - The aim of this study was to assess the within subject reproducibility of cardioventilatory measurements and the maximum permitted 'normal' variability over time at rest and exercise using the respiratory mass spectrometer (RMS). Ten subjects underwent an incremental exercise test on three separate occasions utilising rebreathing (RB) and helium dilution mixed expired gas analysis (HME) functions of the RMS. Measurements included heart rate (HR), oxygen consumption (V(O2)), carbon dioxide excretion (V(VO2)), effective pulmonary blood flow (Q(eff)), stroke volume (SV), arteriovenous oxygen content difference (AVO), transfer factor (Dl(CO)), functional residual capacity (FRC), minute ventilation (VE), tidal volume (VT) and respiratory quotient (RQ). The coefficients of variation for each variable for the 10 subjects were calculated. At rest, the 90th centile variability for measured cardiopulmonary variables (RB only) was <35%. During exercise, the 90th centile for variability for measured cardiopulmonary variables for HME and RB were < or =20 and <40%, respectively. These measurements in healthy adults should inform sample size in research studies. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17188945&query_hl=1 ER - TY - JFULL T1 - Unravelling the mechanisms underpinning chemokine receptor activation and blockade by small molecules: a fine line between agonism and antagonism? A1 - Wise, E A1 - Pease, JE J1 - Biochem Soc Trans Y1 - 2007/08// VL - 35 SN - 0300-5127 SP - 755 EP - 759 N2 - Chemokines are a family of small basic proteins which induce the directed migration of cells, notably leucocytes, by binding to specific GPCRs (G-protein-coupled receptors). Both chemokines and their receptors have been implicated in a host of clinically important diseases, leading to the notion that antagonism of the chemokine-chemokine receptor network may be therapeutically advantageous. Consequently, considerable effort has been put into the development of small-molecule antagonists of chemokine receptors and several such compounds have been described in the literature. One curious by-product of this activity has been the description of several small-molecule agonists of the receptors, which are typically discovered following the optimization of lead antagonists. In this review we discuss these findings and conclude that these small-molecule agonists might be exploited to further our understanding of the molecular mechanisms by which chemokine receptors are activated. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17635141&query_hl=1 ER - TY - JFULL T1 - The non-neuronal cholinergic system in the airways: an unappreciated regulatory role in pulmonary inflammation? A1 - Gwilt, CR A1 - Donnelly, LE A1 - Rogers, DF J1 - Pharmacol Ther Y1 - 2007/08// VL - 115 SN - 0163-7258 SP - 208 EP - 222 N2 - The parasympathetic neurotransmitter acetylcholine is also synthesised and secreted by non-neuronal cells and modifies their behaviour. This is termed the "non-neuronal cholinergic system" and is present in airway inflammatory cells. Acetylcholine is predominantly pro-inflammatory for lymphocytes and epithelial cells, anti-inflammatory for mast cells and macrophages, both pro- and anti-inflammatory for monocytes, and variable in neutrophils and eosinophils. Expression and function of components of the non-neuronal cholinergic system, for example cholinoceptors, can be modified by nicotine in cigarette smoke, the inflammation of asthma and chronic obstructive pulmonary disease (COPD), and the drugs used in clinical management of these diseases. The non-neuronal cholinergic system of airway inflammatory cells represents a previously unappreciated regulatory pathway, with immunomodulatory effects that potentially influence the inflammation of asthma and COPD. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17597218&query_hl=1 ER - TY - JFULL T1 - Prolonged preseasonal treatment phase with Grazax sublingual immunotherapy increases clinical efficacy. A1 - Calderon, MA A1 - Birk, AO A1 - Andersen, JS A1 - Durham, SR J1 - Allergy Y1 - 2007/08// VL - 62 SN - 0105-4538 SP - 958 EP - 961 N2 - BACKGROUND: Sublingual immunotherapy treatment with grass allergen tablets (Grazax) is initiated preseasonally without up-dosing and treatment is continued throughout the entire grass pollen season. Aims of the study: The influence of the duration of preseasonal treatment on clinical efficacy obtained within the grass pollen season was investigated. METHODS: Data from three randomized, double-blind, placebo-controlled, multi-centre trials with varying preseasonal treatment periods were analysed. In the grass pollen season, symptom and medication score reductions relative to placebo were calculated and correlated with the duration of the preseasonal treatment period. RESULTS: The analysis was based on data from 934 patients. A significant reduction in seasonal daily rhinoconjunctivitis symptom and medication scores (17%, CI: 1-33% and 23%, CI: 1-47%, P < 0.05) was observed for patients treated with Grazax compared with placebo after approximately 8 weeks of pretreatment. The magnitude of the reductions in rhinoconjunctivitis symptom and medication scores increased with longer duration of preseasonal treatment (P < 0.0001). CONCLUSIONS: Sublingual immunotherapy with Grazax) must be initiated at least 8 weeks prior to the grass pollen season to provide a significant clinical efficacy. A longer preseasonal treatment period (>8 weeks) improves the clinical efficacy (relative to placebo) during the grass pollen season. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17620076&query_hl=1 ER - TY - JFULL T1 - Myocardial pre-synaptic sympathetic function correlates with glucose uptake in the failing human heart. A1 - Mongillo, M A1 - John, AS A1 - Leccisotti, L A1 - Pennell, DJ A1 - Camici, PG J1 - Eur J Nucl Med Mol Imaging Y1 - 2007/08// VL - 34 SN - 1619-7070 SP - 1172 EP - 1177 N2 - PURPOSE: We have previously shown that the myocardium of patients with heart failure (HF) is insulin resistant. Chronic beta-adrenergic stimulation has been implicated in insulin resistance in cultured cardiomyocytes in vitro, where sustained noradrenaline stimulation inhibited insulin-modulated glucose uptake. As the failing heart is characterized by increased sympathetic drive, we hypothesized that there is a correlation between pre-synaptic sympathetic function and insulin sensitivity in the myocardium of patients with HF. METHODS: Eight patients (aged 67 +/- 7 years) with coronary artery disease and left ventricular dysfunction (ejection fraction 44 +/- 10%) underwent function and viability assessment with cardiovascular magnetic resonance. Myocardial glucose utilization (MGU) was measured using positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG). Pre-synaptic noradrenaline re-uptake was measured by calculating [(11)C]meta-hydroxy-ephedrine (HED) volume of distribution (V (d)) with PET. Two groups of healthy volunteers served as controls for the FDG (n = 8, aged 52 +/- 4 years, p < 0.01 vs patients) and HED (n = 8, aged 40 +/- 6 years, p < 0.01 vs patients) data. RESULTS: MGU in patients was reduced in both normal remote (0.44 +/- 0.14 mumol.min(-1).g(-1)) and dysfunctional (0.49 +/- 0.14 mumol.min(-1).g(-1)) segments compared with controls (0.61 +/- 0.7 mumol.min(-1).g(-1); p < 0.001 vs both). HED V (d) was reduced in dysfunctional segments of patients (38.9 +/- 21.2 ml.g(-1)) compared with normal segments (52.2 +/- 19.6 ml.g(-1)) and compared with controls (62.7 +/- 11.3 ml.g(-1)). In patients, regional MGU was correlated with HED V (d). CONCLUSION: The results of this study provide novel evidence of a correlation between cardiac sympathetic function and insulin sensitivity, which may represent one of the mechanisms contributing to insulin resistance in failing human hearts. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17294189&query_hl=1 ER - TY - JFULL T1 - Seasonal allergic rhinitis is associated with a detrimental effect on examination performance in United Kingdom teenagers: Case-control study A1 - Walker, S A1 - Khan-Wasti, S A1 - Fletcher, M A1 - Cullinan, P A1 - Harris, J A1 - Sheikh, A J1 - J ALLERGY CLIN IMMUN Y1 - 2007/08// VL - 120 SN - 0091-6749 SP - 381 EP - 387 N2 - Background: Seasonal allergic rhinitis is common globally, and symptoms have been shown to impair learning ability in children in laboratory conditions. Critical examinations in children are often held in the summer during the peak grass pollen season.Objective: To investigate whether seasonal allergic rhinitis adversely impacts examination performance in United Kingdom teenagers.Methods: Case-control analysis of 1834 students (age 15-17 years; 50% girls) sitting for national examinations. Cases were those who dropped I or more grades in any of 3 core subjects (mathematics, English, and science) between practice (winter) and final (summer) examinations; controls were those whose grades were either unchanged or improved. Associations between allergic rhinitis symptoms, clinician-diagnosed allergic rhinitis, and allergic rhinitis-related medication use, recorded on examination days immediately before the examination, were assessed using multilevel regression models.Results: Between 38% and 43% of students reported symptoms of seasonal allergic rhinitis on any 1 of the examination days. There were 662 cases (36% of students) and 1172 controls. After adjustment, cases were significantly more likely than controls to have had allergic rhinitis symptoms during the examination period (odds ratio [OR], 1.4; 95% CI, 1.1-1.8; P = .002), to have taken any allergic rhinitis medication (OR, 1.4; 95% CI, 1.1-1.7; P = .01), or to have taken sedating antihistamines (OR, 1.7; 95% CI, 1.1-2.8; P = .03).Conclusion: Current symptomatic allergic rhinitis and medication use are associated with a significantly increased of unexpectedly dropping a grade in summer examinations.Clinical implications: This is the first time the relationship between symptomatic allergic rhinitis and poor examination performance has been demonstrated, which has significant implications for clinical practice. ER - TY - JFULL T1 - Analysis of complex flow and the relationship between blood pressure, wall shear stress, and intima-media thickness in the human carotid artery. A1 - Augst, AD A1 - Ariff, B A1 - McG Thom, SA A1 - Xu, XY A1 - Hughes, AD J1 - Am J Physiol Heart Circ Physiol Y1 - 2007/08// VL - 293 SN - 0363-6135 SP - H1031 EP - H1037 N2 - BACKGROUND: Previous clinical studies have observed relationships between increased intima-media thickness (IMT) in the carotid artery, elevated blood pressure, and low wall shear stress (WSS) calculated from the Poiseuille equation. This study used numerical methods to more accurately determine WSS in the carotid artery and to investigate possible determinants of increased IMT. METHODS: IMT [common carotid artery (CCA) and bulb], CCA flow velocity, brachial systolic (SBP) and diastolic blood pressure (DBP), and carotid systolic pressure (cSBP) were measured in 14 healthy subjects (aged 44 +/- 16 yr). Flow patterns in the carotid bifurcation were determined by computational fluid dynamics (CFD) based on three-dimensional ultrasound geometry. Instantaneous and time-averaged wall shear stress (WSS(av)), oscillatory shear index (OSI), and wall shear stress angle gradients (WSSAG) were calculated. RESULTS: IMT was positively related to SBP, DBP, cSBP, and WSSAG and inversely related to WSS(av) in the CCA. In the bulb, IMT was positively related to SBP and cSBP but was not significantly related to WSS(av) or WSSAG. IMT was unrelated to OSI in both the CCA and the bulb. CONCLUSION: Increased carotid artery IMT in healthy subjects with no evidence of focal plaques is primarily a response to elevated pressure. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17449549&query_hl=1 ER - TY - JFULL T1 - Cell-penetrating-peptide-mediated siRNA lung delivery. A1 - Moschos, SA A1 - Williams, AE A1 - Lindsay, MA J1 - Biochem Soc Trans Y1 - 2007/08// VL - 35 SN - 0300-5127 SP - 807 EP - 810 N2 - The therapeutic application of siRNA (short interfering RNA) shows promise as an alternative approach to small-molecule inhibitors for the treatment of human disease. However, the major obstacle to its use has been the difficulty in delivering these large anionic molecules in vivo. A potential approach to solving this problem is the chemical conjugation of siRNA to the cationic CPPs (cell-penetrating peptides), Tat-(48-60) (transactivator of transcription) and penetratin, which have been shown previously to mediate protein and peptide delivery in a host of animal models. In this transaction, we review recent studies on the utility of siRNA for the investigation of protein function in the airways/lung. We show that, despite previous studies showing the utility of cationic CPPs in vitro, conjugation of siRNA to Tat-(48-60) and penetratin failed to increase residual siRNA-mediated knockdown of p38 MAPK (mitogen-activated protein kinase) (MAPK14) mRNA in mouse lung in vivo. Significantly, we will also discuss potential non-specific actions and the induction of immunological responses by CPPs and their conjugates and how this might limit their application for siRNA-mediated delivery in vivo. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17635153&query_hl=1 ER - TY - JFULL T1 - Effects of metoprolol and carvedilol on pre-existing and new onset diabetes in patients with chronic heart failure: data from the Carvedilol Or Metoprolol European Trial (COMET). A1 - Torp-Pedersen, C A1 - Metra, M A1 - Charlesworth, A A1 - Spark, P A1 - Lukas, MA A1 - Poole-Wilson, PA A1 - Swedberg, K A1 - Cleland, JG A1 - Di Lenarda, A A1 - Remme, WJ A1 - Scherhag, A A1 - COMET investigators J1 - Heart Y1 - 2007/08// VL - 93 SN - 1468-201X SP - 968 EP - 973 N2 - BACKGROUND: Beta blocker treatment may worsen glucose metabolism. OBJECTIVE: To study the development of new onset diabetes in a large cohort of patients with heart failure treated with either metoprolol or carvedilol. DESIGN: Prospective and retrospective analysis of a controlled clinical trial. SETTING: Multinational multicentre study. PATIENTS: 3029 patients with chronic heart failure. INTERVENTIONS: Randomly assigned treatment with carvedilol (n = 1511, target dose 50 mg daily) or metoprolol tartrate (n = 1518, target dose 100 mg daily). RESULTS: Diabetic events (diabetic coma, peripheral gangrene, diabetic foot, decreased glucose tolerance or hyperglycaemia) and new onset diabetes (clinical diagnosis, repeated high random glucose level or glucose lowering drugs) were assessed in 2298 patients without diabetes at baseline. Diabetic events occurred in 122/1151 (10.6%) patients in the carvedilol group and 149/1147 (13.0%) patients in the metoprolol group (hazard ratio (HR) = 0.78; 95% confidence interval (CI) 0.61 to 0.99; p = 0.039). New onset diabetes was diagnosed in 119/1151 (10.3%) v 145/1147 (12.6%) cases in the carvedilol and metoprolol treatment groups (HR = 0.78, CI 0.61 to 0.997; p = 0.048), respectively. Patients with diabetes at baseline had an increased mortality compared with non-diabetic subjects (45.3% v 33.9%; HR = 1.45, CI 1.28 to 1.65). Both diabetic and non-diabetic subjects at baseline had a similar reduction in mortality with carvedilol compared with metoprolol (RR = 0.85; CI 0.69 to 1.06 and RR = 0.82; CI 0.71 to 0.94, respectively). CONCLUSION: A high prevalence and incidence of diabetes is found in patients with heart failure over a course of 5 years. New onset diabetes is more likely to occur during treatment with metoprolol than during treatment with carvedilol. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17237130&query_hl=1 ER - TY - JFULL T1 - GDNF in Parkinson disease: an object lesson in the tyranny of type II. A1 - Hutchinson, M A1 - Gurney, S A1 - Newson, R J1 - J Neurosci Methods Y1 - 2007/07/30/ VL - 163 SN - 0165-0270 SP - 190 EP - 192 N2 - Type II errors may be having a significant impact on drug discovery. This is of particular importance in the clinical neurosciences, where endpoints are often subjective scores of disability rather than unequivocal events such as survival. Here we examine a recently published study [Lang AE, Gill S, Patel NK, et al. Randomized controlled study of intraputamenal glial cell-derived neurotrophic factor infusion in Parkinson disease. Ann Neurol 2006;59:459-66] in an area of immense importance to neuroscience. This small study found no detectable clinical benefit from infused intraputamenal GDNF as a treatment for Parkinson disease. However the standard deviation of the accrued data turned out to be considerably higher than had been anticipated in the power analysis performed prior to the study. In order to determine what impact, if any, this had on the conclusions that could be drawn, the actual data were analyzed by means of both the t-test and the rank-based Somers'D. The study was found to be underpowered and thus incapable of ruling out a large effect of GDNF on Parkinson disease. It therefore does not contradict the large effects seen in previous open-label studies. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16876872&query_hl=1 ER - TY - JFULL T1 - Primary ciliary dyskinesia. A1 - Bush, A A1 - Chodhari, R A1 - Collins, N A1 - Copeland, F A1 - Hall, P A1 - Harcourt, J A1 - Hariri, M A1 - Hogg, C A1 - Lucas, J A1 - Mitchison, HM A1 - O'callaghan, C A1 - Phillips, G J1 - Arch Dis Child Y1 - 2007/07/30/ SN - 1468-2044 N2 - Primary ciliary dyskinesia (PCD) is usually inherited as an autosomal recessive, and in classical form presents with upper and lower respiratory tract infection, and mirror image arrangement in around 50% cases. It is becoming appreciated that dysfunction of cilia is implicated in a wider spectrum of disease, including polycystic liver and kidney disease, central nervous system problems including retinopathy and hydrocephalus, and biliary atresia. Cilia are complex structures, containing more than 250 proteins, but recent studies have begun to locate PCD genes scattered throughout the genome. Screening tests for PCD include nasal nitric oxide and in vivo tests of ciliary motility such as the saccharin test. Specific diagnosis requires examination of cilia by light and electron microscopy, with epithelial culture in doubtful cases. This is only available in supra-regional centres, which have recently been centrally funded by NCG in order to provide a comprehensive, free diagnostic service in England. Treatment is unfortunately not evidence based, since there are no randomised controlled clinical trials in this condition, and recommendations are largely extrapolated from cystic fibrosis and other suppurative lung diseases. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17634184&query_hl=1 ER - TY - JFULL T1 - Pre- and post-synaptic sympathetic function in human hibernating myocardium. A1 - John, AS A1 - Mongillo, M A1 - Depre, C A1 - Khan, MT A1 - Rimoldi, OE A1 - Pepper, JR A1 - Dreyfus, GD A1 - Pennell, DJ A1 - Camici, PG J1 - Eur J Nucl Med Mol Imaging Y1 - 2007/07/28/ SN - 1619-7070 N2 - PURPOSE: Impaired pre-synaptic noradrenaline uptake-1 mechanism has been reported in a swine model of hibernating myocardium (HM). To ascertain whether adrenergic neuroeffector abnormalities are present in human HM, we combined functional measurements in vivo using cardiovascular magnetic resonance (CMR) and positron emission tomography (PET) to assess pre- and post-synaptic sympathetic function. METHODS: Twelve patients with coronary artery disease and chronic left ventricular (LV) dysfunction underwent CMR at baseline and 6 months after bypass for assessment of regional and global LV function and identification of segments with reversible dysfunction. Before surgery, myocardial noradrenaline uptake-1 ([(11)C]meta-hydroxy-ephedrine; HED) and beta-adrenoceptor (beta-AR) density ([(11)C]CGP-12177) were measured with PET. Patient PET data were compared with those in 18 healthy controls. RESULTS: The volume of distribution (V(d)) of HED in HM (47.95+/-28.05 ml/g) and infarcted myocardium (42.69+/-25.76 ml/g) was significantly reduced compared with controls (66.09+/-14.48 ml/g). The V(d) of HED in normal myocardium (49.93+/-20.48 ml/g) of patients was also lower than that in controls and the difference was close to statistical significance (p=0.06). Myocardial beta-AR density was significantly lower in HM (5.49+/-2.35 pmol/g), infarcted (4.82+/-2.61 pmol/g) and normal (5.86+/-1.81 pmol/g) segments of patients compared with healthy controls (8.61+/-1.32 pmol/g). CONCLUSION: Noradrenaline uptake-1 mechanism and beta-AR density are reduced in the myocardium of patients with chronic LV dysfunction and evidence of HM. The increased sympathetic activity to the heart in these patients is a generalised rather than regional phenomenon which is likely to contribute to the remodelling process of the whole LV rather than playing a causative role in HM. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17661029&query_hl=1 ER - TY - JFULL T1 - Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma. A1 - Moffatt, MF A1 - Kabesch, M A1 - Liang, L A1 - Dixon, AL A1 - Strachan, D A1 - Heath, S A1 - Depner, M A1 - von Berg, A A1 - Bufe, A A1 - Rietschel, E A1 - Heinzmann, A A1 - Simma, B A1 - Frischer, T A1 - Willis-Owen, SA A1 - Wong, KC A1 - Illig, T A1 - Vogelberg, C A1 - Weiland, SK A1 - von Mutius, E A1 - Abecasis, GR A1 - Farrall, M A1 - Gut, IG A1 - Lathrop, GM A1 - Cookson, WO J1 - Nature Y1 - 2007/07/26/ VL - 448 SN - 1476-4687 SP - 470 EP - 473 N2 - Asthma is caused by a combination of poorly understood genetic and environmental factors. We have systematically mapped the effects of single nucleotide polymorphisms (SNPs) on the presence of childhood onset asthma by genome-wide association. We characterized more than 317,000 SNPs in DNA from 994 patients with childhood onset asthma and 1,243 non-asthmatics, using family and case-referent panels. Here we show multiple markers on chromosome 17q21 to be strongly and reproducibly associated with childhood onset asthma in family and case-referent panels with a combined P value of P < 10(-12). In independent replication studies the 17q21 locus showed strong association with diagnosis of childhood asthma in 2,320 subjects from a cohort of German children (P = 0.0003) and in 3,301 subjects from the British 1958 Birth Cohort (P = 0.0005). We systematically evaluated the relationships between markers of the 17q21 locus and transcript levels of genes in Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines from children in the asthma family panel used in our association study. The SNPs associated with childhood asthma were consistently and strongly associated (P < 10(-22)) in cis with transcript levels of ORMDL3, a member of a gene family that encodes transmembrane proteins anchored in the endoplasmic reticulum. The results indicate that genetic variants regulating ORMDL3 expression are determinants of susceptibility to childhood asthma. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17611496&query_hl=1 ER - TY - JFULL T1 - Lay educators in asthma self management: Reflections on their training and experiences. A1 - Brown, C A1 - Hennings, J A1 - Caress, AL A1 - Partridge, MR J1 - Patient Educ Couns Y1 - 2007/07/25/ SN - 0738-3991 N2 - OBJECTIVE: To capture the experiences and feelings of lay educators in an asthma self-management programme to aid understanding of optimal methods of recruitment, training and retention, and to enhance their value within the programme. METHODS: A multi site randomised controlled equivalence trial of asthma educators and primary care practice based nurses during which the educators were asked to keep a diary of their experience. A qualitative thematic analysis of these diaries was undertaken. RESULTS: Eight lay educators supplied diaries. From these diaries emerged personal reasons for involvement in the programme, constructive comments on the training programme, a need for preparation for the realities of clinical practice and significant ongoing support and training. CONCLUSION: Lay educators are a potential resource for giving self-management education to patients with long-term conditions such as asthma. However, there are some considerations that need to be taken into account regarding contracts, retention and continual support. PRACTICE IMPLICATIONS: Lay educators need a flexible but comprehensive training programme, contracts, on site mentoring and support. They seem most contented when welcomed by health professionals and treated as part of the team. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17662568&query_hl=1 ER - TY - JFULL T1 - Prediction of mode of death in heart failure: the Seattle Heart Failure Model. A1 - Mozaffarian, D A1 - Anker, SD A1 - Anand, I A1 - Linker, DT A1 - Sullivan, MD A1 - Cleland, JG A1 - Carson, PE A1 - Maggioni, AP A1 - Mann, DL A1 - Pitt, B A1 - Poole-Wilson, PA A1 - Levy, WC J1 - Circulation Y1 - 2007/07/24/ VL - 116 SN - 1524-4539 SP - 392 EP - 398 N2 - BACKGROUND: Prognosis and mode of death in heart failure patients are highly variable in that some patients die suddenly (often from ventricular arrhythmia) and others die of progressive failure of cardiac function (pump failure). Prediction of mode of death may facilitate decisions about specific medications or devices. METHODS AND RESULTS: We used the Seattle Heart Failure Model (SHFM), a validated prediction model for total mortality in heart failure, to assess the mode of death in 10,538 ambulatory patients with New York Heart Association class II to IV heart failure and predominantly systolic dysfunction enrolled in 6 randomized trials or registries. During 16,735 person-years of follow-up, 2014 deaths occurred, which included 1014 sudden deaths and 684 pump-failure deaths. Compared with a SHFM score of 0, patients with a score of 1 had a 50% higher risk of sudden death, patients with a score of 2 had a nearly 3-fold higher risk, and patients with a score of 3 or 4 had a nearly 7-fold higher risk (P<0.001 for all comparisons; 1-year area under the receiver operating curve, 0.68). Stratification of risk of pump-failure death was even more pronounced, with a 4-fold higher risk with a score of 1, a 15-fold higher risk with a score of 2, a 38-fold higher risk with a score of 3, and an 88-fold higher risk with a score of 4 (P<0.001 for all comparisons; 1-year area under the receiver operating curve, 0.85). The proportion of deaths caused by sudden death versus pump-failure death decreased from a ratio of 7:1 with a SHFM score of 0 to a ratio of 1:2 with a SHFM score of 4 (P trend <0.001). CONCLUSIONS: The SHFM score provides information about the likely mode of death among ambulatory heart failure patients. Investigation is warranted to determine whether such information might predict responses to or cost-effectiveness of specific medications or devices in heart failure patients. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17620506&query_hl=1 ER - TY - JFULL T1 - Motion-compensated MR valve imaging with COMB tag tracking and super-resolution enhancement. A1 - Dowsey, AW A1 - Keegan, J A1 - Lerotic, M A1 - Thom, S A1 - Firmin, D A1 - Yang, GZ J1 - Med Image Anal Y1 - 2007/07/24/ SN - 1361-8415 N2 - Understanding the morphology and function of heart valves is important to the study of underlying causes of heart failure. Existing techniques such as those based on echocardiography are limited by the relatively low signal-to-noise ratio (SNR), attenuation artefacts, and restricted access. The alternative of cardiovascular MR imaging offers versatility and accuracy in 3D localisation, but is hampered by large movements of the valves throughout the cardiac cycle. This paper presents a motion-compensated adaptive imaging approach for MR valve imaging. To illustrate its clinical potential, 3D motion of the aortic valve plane is first captured through a single breath-hold COMB tag pre-scan and then tracked in real-time with an automatic method based on multi-resolution image registration. Motion-compensated coverage of the aortic valve is then acquired prospectively, thus allowing its clear 3D reconstruction and visualisation. To provide isotropic voxel coverage of the imaging volume, retrospective projection onto convex sets (POCS) super-resolution enhancement is applied to the slice-select direction. In vivo results demonstrate the effectiveness of the proposed motion-compensation and super-resolution schemes for depicting the structure of the valve leaflets throughout the cardiac cycle. The proposed method fundamentally changes the way MR imaging is performed by transforming it from a spatially to materially localised imaging method. This also has important implications for quantifying blood flow and myocardial perfusion, as well as tracking anatomy and function of the heart. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17804277&query_hl=1 ER - TY - JFULL T1 - Impact of protein acetylation in inflammatory lung diseases. A1 - Ito, K A1 - Charron, CE A1 - Adcock, IM J1 - Pharmacol Ther Y1 - 2007/07/24/ SN - 0163-7258 N2 - Chronic inflammatory lung diseases are characterized by increased expression of multiple inflammatory genes following activation by proinflammatory transcription factors, such as nuclear factor kappaB (NF-kappaB) and AP-1. Gene expression is, at least in part, regulated by acetylation of core histones through the action of coactivators, such as CREB-binding protein (CBP), which have intrinsic histone acetyltransferase (HAT) activity. Conversely gene repression is mediated via a combination of histone deacetylases (HDAC) and other corepressors. In asthma, the level of HAT activity is elevated in bronchial biopsies, whereas HDAC activity levels are only partially reduced and inhaled corticosteroids are able to reduce the increased HAT activity back to those seen in normal subjects. In contrast, in chronic obstructive pulmonary disease (COPD), there is a greater reduction in HDAC activity and HDAC2 expression but no difference in HAT activity. HAT and HDAC are also reported to modify a large and expanding number of nonhistone proteins, including nuclear import proteins, chaperones, cytoskeletal proteins, and other transcriptional factors, such as NF-kappaB and signal transducer and activation of transcription (STAT). Acetylation regulates several aspects of protein function and stability leading to differing effects on inflammatory gene expression and cell recruitment involved in the pathogenesis of inflammatory diseases. This review will examine the impact of acetylation on the function of key proteins involved in airway inflammatory disease and the effects of current therapies on acetylation status of key proteins. Further appreciation of the role of these changes may lead to the development of novel therapeutic approaches to inflammatory lung diseases that are currently difficult to treat. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17720252&query_hl=1 ER - TY - JFULL T1 - Relationship of connexin43 expression to phenotypic modulation in cultured human aortic smooth muscle cells. A1 - Matsushita, T A1 - Rama, A A1 - Charolidi, N A1 - Dupont, E A1 - Severs, NJ J1 - Eur J Cell Biol Y1 - 2007/07/23/ SN - 0171-9335 N2 - Transition of arterial smooth muscle cells from the contractile to the synthetic phenotype in vivo is associated with up-regulation of the gap-junctional protein, connexin43 (Cx43). However, the role of increased Cx43 expression in relation to the characteristic features of the synthetic phenotype - altered growth, differentiation or synthetic activity - has not previously been defined. In the present study, growth was induced in cultured human aortic smooth muscle cells by treatment with thrombin and with PDGF-bb; growth arrest was induced by serum deprivation and contact inhibition. Alterations in Cx43 expression and gap-junctional communication were analyzed in relation to expression of markers for contractile differentiation and extracellular matrix synthesis. Treatment with thrombin, but not PDGF-bb, led to up-regulation of Cx43 gap junctions, increased synthetic activity yet also enhanced contractile differentiation. Inhibition of growth by deprivation of serum growth factors in sub-confluent cultures had no effect on Cx43 expression or contractile differentiation. Growth arrest by contact inhibition led to progressive reduction in Cx43 expression, in parallel with progressive increase in expression of differentiation markers but no alteration in synthetic activity. Of a range of stimuli examined, only thrombin had the combined effect of increasing Cx43 gap-junction communication, growth and synthesis, yet it also enhanced contractile differentiation. Down-regulation of Cx43 and improved contractile differentiation occurred only when growth arrest was induced through the contact-inhibition pathway, though, in this instance, synthesis remained undiminished. We conclude that Cx43 levels, though having common correlates, are not exclusively linked to the cell phenotype or the state of growth. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17651863&query_hl=1 ER - TY - JFULL T1 - Pulmonary endothelium dependent vasodilation emerges after birth in mice. A1 - Faro, R A1 - Moreno, L A1 - Hislop, AA A1 - Sturton, G A1 - Mitchell, JA J1 - Eur J Pharmacol Y1 - 2007/07/19/ VL - 567 SN - 0014-2999 SP - 240 EP - 244 N2 - At birth, with the first breath, pulmonary vessels undergo profound adaptive processes. A failure in the ability of pulmonary vessels to adapt at birth results in persistent pulmonary hypertension of the new born. The mechanisms regulating pulmonary adaptation at birth are still unclear. Progress in this area is slow, not least because genetically modified mice have not yet been used to address questions in this area of research, principally because pulmonary vessels in new born mice are very small making the study of dilator response in vitro difficult. In the current study we have used precision cut lung slices to characterise the functional vasomotor changes in lung vessels of new born mice (1-4 days old), 8-15 day old mice or adult mice. The internal luminal area of pulmonary artery and airways was measured digitally. Vasoconstriction and vasodilatation were expressed as the percentage change in internal luminal area compared with the control area. The thromboxane A(2) mimetic U-46619 (3x10(-7) M) caused a significant vasoconstriction in vessels of all groups. However, acetylcholine (3x10(-5) M) induced arterial dilation only in the 8-15 days, and adult groups. By contrast, sodium nitroprusside, which acts independently of the endothelium, was an effective vasodilator in lung vessels from neonates. These data are the first to characterise the development of endothelium dependent vasodilatation in lung after birth in mice. This approach can be used with genetically modified mice, which is important to further our understanding of the physiology in this area. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17540365&query_hl=1 ER - TY - JFULL T1 - Small molecule receptor agonists and antagonists of CCR3 provide insight into mechanisms of chemokine receptor activation. A1 - Wise, EL A1 - Duchesnes, C A1 - da Fonseca, PC A1 - Allen, RA A1 - Williams, TJ A1 - Pease, JE J1 - J Biol Chem Y1 - 2007/07/16/ SN - 0021-9258 N2 - Chemokine receptor CCR3 is highly expressed by eosinophils and signals in response to binding of the eotaxin family of chemokines, which are upregulated in allergic disorders. Consequently, CCR3 blockade is of interest as a possible therapeutic approach for the treatment of allergic disease. We have described previously a bi-specific antagonist of CCR1 and CCR3 named UCB35625, which was proposed to interact with the transmembrane residues Y41, Y113 and E287 of CCR1, all of which are conserved in CCR3. Here, we show that cells expressing the CCR3 constructs Y113A and E287Q are insensitive to antagonism by UCB35625 and also exhibit impaired chemotaxis in response to CCL11/Eotaxin suggesting that these residues are important for antagonist binding and also receptor activation. Furthermore, mutation of the residue Y113 to alanine was found to turn the antagonist UCB35625 into a CCR3 agonist. Screens of small molecule libraries identified a novel specific agonist of CCR3 named CH0076989. This was able to activate eosinophils and transfectants expressing both wild-type CCR3 and a CCR1:CCR3 chimaeric receptor lacking the CCR3 amino-terminus, indicating that this region of CCR3 is not required for CH0076989 binding. A direct interaction with the transmembrane helices of CCR3 was supported by mutation of the residues Y41, Y113 and E287 which resulted in complete loss of CH0076989 activity, suggesting that the compound mimics activation by CCL11. We conclude that both agonists and antagonists of CCR3 appear to occupy overlapping sites within the transmembrane helical bundle, suggesting a fine line between agonism and antagonism of chemokine receptors. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17635911&query_hl=1 ER - TY - JFULL T1 - Influence of Pulsatile Flow on LDL Transport in the Arterial Wall. A1 - Sun, N A1 - Wood, NB A1 - Hughes, AD A1 - Thom, SA A1 - Xu, XY J1 - Ann Biomed Eng Y1 - 2007/07/14/ SN - 0090-6964 N2 - The accumulation of low-density lipoprotein (LDL) is one of the important factors in atherogenesis. Two different time scales may influence LDL transport in vivo: (1) LDL transport is coupled to blood flow with a pulse cycle of around 1 s in humans; (2) LDL transport within the arterial wall is mediated by transmural flow in the order of 10(-8) m/s. Most existing models have assumed steady flow conditions and overlooked the interactions between physical phenomena with different time scales. The objective of this study was to investigate the influence of pulsatile flow on LDL transport and examine the validity of steady flow assumption. The effect of pulsatile flow on transmural transport was incorporated by using a lumen-free cyclic (LFC) and a lumen-free time-averaged (LFTA) procedures. It is found that the steady flow simulation predicted a focal distribution in the post-stenotic region, differing from the diffuse distribution pattern produced by the pulsatile flow simulation. The LFTA procedure, in which time-averaged shear-dependent transport properties calculated from instantaneous wall shear stress (WSS) were used, predicted a similar distribution pattern to the LFC simulations. We conclude that the steady flow assumption is inadequate and instantaneous hemodynamic conditions have important influence on LDL transmural transport in arterial geometries with disturbed and complicated flow patterns. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17629792&query_hl=1 ER - TY - JFULL T1 - Role of TLR2, TLR4 and MyD88 in ozone-induced airway hyperresponsiveness and neutrophilia. A1 - Williams, AS A1 - Leung, SY A1 - Nath, P A1 - Khorasani, NM A1 - Bhavsar, P A1 - Issa, R A1 - Mitchell, JA A1 - Adcock, IM A1 - Chung, KF J1 - J Appl Physiol Y1 - 2007/07/12/ SN - 8750-7587 N2 - Exposure to air pollutants such as ozone (O3) induces airway hyperresponsiveness (AHR) and airway inflammation. Toll-like Receptors (TLR) are first-line effector molecules in innate immunity to infections and signal via adapter proteins, including myeloid differentiation factor-88 (MyD88). We investigated the sensing of ozone by TLR2, TLR4 and MyD88. Ozone induced AHR in wild-type (WT) C57BL/6 mice, but AHR was absent in TLR2(-/-), TLR4(-/-) and MyD88(-/-) mice. Bronchoalveolar lavage (BAL) neutrophilia induced by ozone was inhibited at 3 hr but not at 24 hr in TLR2 and TLR4(-/-) mice, while in MyD88(-/-) mice, this was inhibited at 24 hr. We investigated the expression of inflammatory cytokines, and TLR2, TLR4 and MyD-88 in these mice. Ozone induced time-dependent increases in inflammatory gene expression of KC and IL-6, and of TLR2, TLR4 and MyD88 in WT mice. IL-6 and KC expression induced by ozone was inhibited in TLR2(-/-), TLR4(-/-) and MyD88(-/-) mice. Expression of MyD88 was increased in TLR2 and TLR4(-/-) mice, whilst induction of TLR2 or TLR4 was reduced in TLR2(-/-) and TLR4(-/-) mice, respectively. TLR2 and TLR4 mediate AHR induced by oxidative stress such as ozone, while the adapter protein MyD88, but not TLR2 or TLR4, is important in mediating ozone-induced neutrophilia. TLR2 and TLR4 may also be important in regulating the speed of neutrophilic response. Therefore, ozone may induce AHR and neutrophilic inflammation through the activation of the toll-like receptor pathway that may sense non-infectious stimuli such as oxidative stress. Key words: toll-like receptors, myeloid differentiation factor 88, ozone, bronchial hyperresponsiveness, oxidative stress. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17626835&query_hl=1 ER - TY - JFULL T1 - Chemotactic action of prostaglandin E2 on mouse mast cells acting via the PGE2 receptor 3. A1 - Weller, CL A1 - Collington, SJ A1 - Hartnell, A A1 - Conroy, DM A1 - Kaise, T A1 - Barker, JE A1 - Wilson, MS A1 - Taylor, GW A1 - Jose, PJ A1 - Williams, TJ J1 - Proc Natl Acad Sci U S A Y1 - 2007/07/10/ VL - 104 SN - 0027-8424 SP - 11712 EP - 11717 N2 - Mast cells are long-lived cells that are principally recognized for their effector function in helminth infections and allergic reactions. These cells are derived from pluripotential hematopoietic stem cells in the bone marrow that give rise to committed mast cell progenitors in the blood and are recruited to tissues, where they mature. Little is known about the chemotactic signals responsible for recruitment of progenitors and localization of mature mast cells. A mouse model was set up to identify possible mast cell progenitor chemoattractants produced during repeated allergen challenge in vivo. After the final challenge, the nasal mucosa was removed to produce conditioned medium, which was tested in chemotaxis assays against 2-wk murine bone marrow-derived c-kit+ mast cells (BMMC). A single peak of chemotactic activity was seen on reverse-phase HPLC with a retention time and electrospray mass spectrum consistent with prostaglandin E2 (PGE2). This lipid was found to be a highly potent chemoattractant for immature (2-wk) and also mature (10-wk) BMMC in vitro. Fluorescently labeled 2-wk c-kit+ BMMC, when injected intravenously, accumulated in response to intradermally injected PGE2. Analysis using TaqMan showed mRNA expression of the PGE2 receptors 3 (EP3) and 4 (EP4) on 2- and 10-wk BMMC. Chemotaxis induced by PGE2 was mimicked by EP3 agonists, blocked by an EP3 receptor antagonist, and partially inhibited by a MAPKK inhibitor. These results show an unexpected function for PGE2 in the chemotaxis of mast cells. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17606905&query_hl=1 ER - TY - JFULL T1 - Fluticasone, but not salmeterol, reduces cigarette smoke-induced production of interleukin-8 in human airway smooth muscle. A1 - Oltmanns, U A1 - Walters, M A1 - Sukkar, M A1 - Xie, S A1 - Issa, R A1 - Mitchell, J A1 - Johnson, M A1 - Chung, KF J1 - Pulm Pharmacol Ther Y1 - 2007/07/10/ SN - 1094-5539 N2 - Cigarette smoke is the leading risk factor for the development of chronic obstructive pulmonary disease. We have recently shown that cigarette smoke extract synergises with tumour necrosis factor alpha (TNFalpha) in the induction of interleukin-8 (IL-8) from human airway smooth muscle cells. We have investigated the effect of fluticasone propionate, a corticosteroid, and salmeterol, a beta(2)-adrenergic receptor agonist, on cigarette smoke extract-induced IL-8 production by human airway smooth muscle cells. Human airway smooth muscle cells in primary culture were exposed to cigarette smoke extract and/or TNFalpha (1ngml(-1)) with and without pretreatment with fluticasone (10(-13)-10(-8)M) and/or salmeterol (10(-11)-10(-6)M). IL-8 was analysed by ELISA. Fluticasone dose-dependently inhibited IL-8 release induced by cigarette smoke extract, TNFalpha or combined cigarette smoke extract and TNFalpha. However, while IL-8 release in the presence of cigarette smoke extract alone was completely inhibited by fluticasone, IL-8 production induced by cigarette smoke extract and TNFalpha was only partially reduced. Salmeterol alone had no effect on cigarette smoke extract and/or TNFalpha-induced IL-8 production from human airway smooth muscle cells. Combined fluticasone and salmeterol did not cause further inhibitory effects compared to fluticasone alone. Fluticasone but not salmeterol is effective in reducing cigarette smoke extract-induced IL-8 production in human airway smooth muscle cells. The reduced inhibition of cigarette smoke extract- and TNFalpha-induced IL-8 release by fluticasone may explain why corticosteroids are less effective in chronic obstructive pulmonary disease where increased amounts of TNFalpha are present. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17692547&query_hl=1 ER - TY - JFULL T1 - Antihypertensive-associated incident diabetes: controversy persists. A1 - Gupta, AK A1 - Poulter, NR J1 - Arch Intern Med Y1 - 2007/07/09/ VL - 167 SN - 0003-9926 SP - 1433; author reply 1434 EP - 1435; author reply 1434 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17620540&query_hl=1 ER - TY - JFULL T1 - Allergic Rhinitis and Onset of Bronchial Hyperresponsiveness: A Population-based Study. A1 - Shaaban, R A1 - Zureik, M A1 - Soussan, D A1 - Anto, JM A1 - Heinrich, J A1 - Janson, C A1 - Kunzli, N A1 - Sunyer, J A1 - Wjst, M A1 - Burney, PG A1 - Neukirch, F A1 - Leynaert, B J1 - Am J Respir Crit Care Med Y1 - 2007/07/05/ SN - 1073-449X N2 - RATIONALE: Patients with allergic rhinitis have more frequent bronchial hyper-responsiveness (BHR) in cross-sectional studies. OBJECTIVE: To estimate the changes in BHR in non-asthmatic subjects with and without allergic rhinitis during a 9-year period. METHODS: BHR onset was studied in 3,719 subjects without BHR at baseline, who participated in the follow-up of the European Community Respiratory Health Survey. MEASUREMENTS: BHR was defined as a >/=20% decrease in FEV1 for a maximum dose of 1 mg of methacholine. Allergic rhinitis was defined as having a history of nasal allergy and positive specific IgE (>0.35UI/ml) to pollen, cat, mites or cladosporium. MAIN RESULTS: The cumulative incidence of BHR was 9.7% in subjects with allergic rhinitis, 7.0% in subjects with atopy but no rhinitis, compared to 5.5% in subjects without allergic rhinitis and atopy (respective odds-ratio (OR) ) for BHR onset 2.44 [1.73-3.45] and 1.35 [0.86-2.11], after adjustment for potential confounders including sex, smoking, BMI and FEV1. Subjects with rhinitis sensitised exclusively to cat or to mites were particularly at increased risk of developing BHR (ORs: 7.90 [3.48-17.93] and 2.84 [1.36-5.93] respectively). Conversely, in subjects with BHR at baseline (N=372), 35.3% of those with allergic rhinitis, compared to 51.8% of those without rhinitis had no more BHR at follow-up; OR=0.51 [0.33-0.78]. BHR "remission" was more frequent in patients with rhinitis treated by nasal steroids than in those not treated (OR= 0.33 [0.14-0.75]). CONCLUSIONS: Allergic rhinitis was associated with increased onset of BHR, and less chance for remission except in those treated for rhinitis. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17615387&query_hl=1 ER - TY - JFULL T1 - Salt intake and hypertension in Chile: the need for health interventions A1 - Garcia-Larsen, V. A1 - Zarate, V. A1 - Jimenez de la Jara, J. J1 - BMJ Y1 - 2007/07/04/ UR - http://www.bmj.com/cgi/eletters?lookup=by_date&days=5&ck=nck#171023 ER - TY - JFULL T1 - Images in cardiovascular medicine. An unusual site for a common disease. A1 - Alzetani, M A1 - Boyle, JJ A1 - Lefroy, D A1 - Nihoyannopoulos, P J1 - Circulation Y1 - 2007/07/03/ VL - 116 SN - 1524-4539 SP - e1 EP - e1 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17606848&query_hl=1 ER - TY - JFULL T1 - Therapeutics of vein graft intimal hyperplasia: 100 years on. A1 - Wallitt, EJ A1 - Jevon, M A1 - Hornick, PI J1 - Ann Thorac Surg Y1 - 2007/07// VL - 84 SN - 1552-6259 SP - 317 EP - 323 N2 - Intimal hyperplasia is central to the pathology of vein graft re-stenosis, and despite considerable advances in our understanding of vascular biology since it was first described 100 years ago, it is still a significant clinical problem. Recent decades have seen the development of many new therapeutic agents aimed at treating this condition, but the successes of laboratory studies have not been replicated in the clinic yet. This review discusses these therapeutic agents, how their modes of action relate to the pathogenesis of vein graft intimal hyperplasia, and considerations of ways in which such therapy may be improved in the future. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17588453&query_hl=1 ER - TY - JFULL T1 - Recorded infections and antibiotics in early life: associations with allergy in UK children and their parents. A1 - Harris, JM A1 - Mills, P A1 - White, C A1 - Moffat, S A1 - Newman Taylor, AJ A1 - Cullinan, P J1 - Thorax Y1 - 2007/07// VL - 62 SN - 0040-6376 SP - 631 EP - 637 N2 - BACKGROUND: It is suggested that the inverse relationship between allergic disease and family size reflects reduced exposure to early life infections, and that antibiotic treatment in childhood diminishes any protective effect of such infection. METHODS: A birth cohort study was undertaken in 642 children recruited before birth and seen annually until the age of 8 years. Reported infections and prescribed antibiotics by the age of 5 years were counted from GP records and comparisons were made with a previous study of their parents. RESULTS: At the age of 8 years, 104 children (19%) were atopic, 79 (13%) were currently wheezy and 124 (21%) had seasonal rhinitis. 577 children (97%) had at least three infections recorded by age 5, a figure much higher than that of their parents (69%). By the age of 5 only 11 children (2%) had never received a prescription for antibiotics; the corresponding figure for the parents was 24%. Higher numbers of infections were recorded for firstborn children. After adjusting for parental atopy and birth order, there was no association between infection counts and atopy (OR 1.01 (95% CI 0.99 to 1.03) per infection). Significant positive associations were found for wheeze and seasonal rhinitis. An increased risk of current wheeze was found for each antibiotic prescription (adjusted OR 1.07 (95% CI 1.03 to 1.10)) but not for atopy. This was primarily explained by prescriptions for respiratory infections. Similar patterns were observed for seasonal rhinitis. CONCLUSIONS: Despite very high rates of recorded early life infections and antibiotic prescriptions, no plausibly causative relationships were found with subsequent respiratory allergies. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17289862&query_hl=1 ER - TY - JFULL T1 - Glycosaminoglycan synthesis by mesenchymal stem cells in response to stretch A1 - New, SEP A1 - Chester, AH A1 - Yacoub, MH A1 - Taylor, PM J1 - TISSUE ENG Y1 - 2007/07// VL - 13 SN - 1076-3279 SP - 1702 EP - 1702 ER - TY - JFULL T1 - Resource utilization implications of treatment were able to be assessed from appropriately reported clinical trial data. A1 - Poole-Wilson, PA A1 - Kirwan, BA A1 - Vokó, Z A1 - de Brouwer, S A1 - Dunselman, PH A1 - van Dalen, FJ A1 - Lubsen, J A1 - ACTION (A Coronary disease Trial Investigating Outcome with Nifedipine GITS) investigators J1 - J Clin Epidemiol Y1 - 2007/07// VL - 60 SN - 0895-4356 SP - 727 EP - 733 N2 - BACKGROUND AND OBJECTIVE: Published clinical trial data rarely allow assessment of the health care resource utilization implications of treatment. We give an example of how these can be assessed given appropriate tabulation of data. METHODS: Data from a trial comparing long-acting nifedipine gastrointestinal therapeutic system to placebo in 7,665 patients with stable angina pectoris was analyzed. RESULTS: Relative to placebo, nifedipine significantly increased mean cardiovascular (CV) event-free survival by 41 days but had no effect on mean survival. Per 100 years of follow-up, 78.1 patient-years of double-blind nifedipine administration reduced use of another calcium antagonist, an angiotensin converting enzyme inhibitor, an angiotensin receptor blocker, a diuretic and a cardiac glycoside by 1.54, 3.73, 2.63, 2.23, and 0.64 years, respectively, whereas 0.21 less hospitalization for overt heart failure, 0.47 less hospitalization for any stroke or transient ischemic attack, 0.8 less coronary angiogram, 0.38 less coronary bypass procedure, and 0.13 additional orthopedic procedure was required. Combining resource utilization with cost data for one particular hospital showed that one additional year of CV event-free survival costs an average additional euro 3,036 in the setting considered. CONCLUSION: Appropriately tabulated clinical trial data allows clinicians to judge the resource utilization implications and economic effect of treatment decisions. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17573989&query_hl=1 ER - TY - JFULL T1 - Natural killer cells, killer immunoglobulin-like receptors and human leucocyte antigen class I in disease. A1 - Boyton, RJ A1 - Altmann, DM J1 - Clin Exp Immunol Y1 - 2007/07// VL - 149 SN - 0009-9104 SP - 1 EP - 8 N2 - Natural killer cells constitute a potent, rapid part of the innate immune response to infection or transformation, and also generate a link to priming of adaptive immunity. Their function can encompass direct cytotoxicity as well as the release of cytokines and chemokines. In humans, a major component of natural killer (NK) cell target recognition depends mainly on the surveillance of human leucocyte antigen (HLA) class I molecules by killer immunoglobulin-like receptors (KIR). Different KIR can transmit inhibitory or activatory signals to the cell, and effector function is considered to result from the balance of these contributing signals. The regulation of NK cell responses depends on a number of variables: KIR genotype, HLA genotype, heterozygosity versus homozygosity for these, whether there is cognate recognition between the HLA and KIR products carried by an individual, clonal variation between individual NK cells in KIR expression, and the specific modulation of HLA expression by infection, transformation or peptide binding. Different HLA/KIR genotypes can impart different thresholds of activation to the NK cell repertoire and such genotypic variation has been found to confer altered risk in a number of diseases including human immunodeficiency virus (HIV) susceptibility and progression, hepatitis C virus clearance, idiopathic bronchiectasis, autoimmunity and cancer. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17521317&query_hl=1 ER - TY - JFULL T1 - Effect of inhaled interleukin-5 on eosinophil progenitors in the bronchi and bone marrow of asthmatic and non-asthmatic volunteers. A1 - Menzies-Gow, AN A1 - Flood-Page, PT A1 - Robinson, DS A1 - Kay, AB J1 - Clin Exp Allergy Y1 - 2007/07// VL - 37 SN - 0954-7894 SP - 1023 EP - 1032 N2 - BACKGROUND: Asthma is characterized by increases in mature eosinophils and their progenitors within the bronchus and bone marrow. IL-5 plays a key role in eosinophil development in the bone marrow and at the site of allergic inflammation. We therefore studied the effects of nebulized IL-5 on eosinophils, their progenitors and in situ haemopoiesis within the airway and bone marrow. METHODS: Nine atopic asthmatics and 10 non-atopic non-asthmatic control volunteers inhaled 10 microg of IL-5 or placebo via a nebulizer in a double-blind, randomized, cross-over study. Bronchoscopy, bone marrow aspiration and peripheral blood sampling were performed 24 h after nebulization. Four weeks later, volunteers inhaled the alternative solution and underwent a repeat bronchoscopy and bone marrow aspiration. RESULTS: Inhalation of IL-5 significantly decreased CD34(+)/IL-5Ralpha mRNA(+) cells within the bronchial mucosa and the percentage of CD34(+) cells that were CCR3(+) within the bone marrow of atopic asthmatic, but not control, volunteers. Inhalation of IL-5 also induced a significant increase in bronchial mucosal eosinophils in the non-atopic non-asthmatic control volunteers, but not in the asthmatics. IL-5 had no effect on spirometry or airways hyper-reactivity in either group. CONCLUSIONS: Inhaled IL-5 modulated eosinophil progenitor numbers in both the airways and bone marrow of asthmatics and induced local eosinophilia in non-asthmatics. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17581195&query_hl=1 ER - TY - JFULL T1 - Mechanisms of induction of airway smooth muscle hyperplasia by transforming growth factor-beta. A1 - Xie, S A1 - Sukkar, MB A1 - Issa, R A1 - Khorasani, NM A1 - Chung, KF J1 - Am J Physiol Lung Cell Mol Physiol Y1 - 2007/07// VL - 293 SN - 1040-0605 SP - L245 EP - L253 N2 - Airway smooth muscle (ASM) hyperplasia is a characteristic feature of the asthmatic airway, but the underlying mechanisms that induce ASM hyperplasia remain unknown. Because transforming growth factor (TGF)-beta is a potent regulator of ASM cell proliferation, we determined its expression and mitogenic signaling pathways in ASM cells. We obtained ASM cells by laser capture microdissection of bronchial biopsies and found that ASM cells from asthmatic patients expressed TGF-beta1 mRNA and protein to a greater extent than nonasthmatic individuals using real-time RT-PCR and immunohistochemistry, respectively. TGF-beta1 stimulated the growth of nonconfluent and confluent ASM cells either in the presence or absence of serum in a time- and concentration-dependent manner. The mitogenic activity of TGF-beta1 on ASM cells was inhibited by selective inhibitors of TGF-beta receptor I kinase (SD-208), phosphatidylinositol 3-kinase (PI3K, LY-294002), ERK (PD-98059), JNK (SP-600125), and NF-kappaB (AS-602868). On the other hand, p38 MAPK inhibitor (SB-203580) augmented TGF-beta1-induced proliferation. To study role of the Smads, we transduced ASM cells with an adenovirus vector-expressing Smad4, Smad7, or dominant-negative Smad3 and found no involvement of these Smads in TGF-beta1-induced proliferation. Dexamethasone caused a dose-dependent inhibition in TGF-beta1-induced proliferation. Our findings suggest that TGF-beta1 may act in an autocrine fashion to induce ASM hyperplasia, mediated by its receptor and several kinases including PI3K, ERK, and JNK, whereas p38 MAPK is a negative regulator. NF-kappaB is also involved in the TGF-beta1 mitogenic signaling, but Smad pathway does not appear important. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17468136&query_hl=1 ER - TY - JFULL T1 - Tolerability and dose-related effects of nebivolol in elderly patients with heart failure: data from the Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalisation in Seniors with Heart Failure (SENIORS) trial. A1 - Dobre, D A1 - van Veldhuisen, DJ A1 - Mordenti, G A1 - Vintila, M A1 - Haaijer-Ruskamp, FM A1 - Coats, AJ A1 - Poole-Wilson, PA A1 - Flather, MD A1 - SENIORS Investigators J1 - Am Heart J Y1 - 2007/07// VL - 154 SN - 1097-6744 SP - 109 EP - 115 N2 - BACKGROUND: The SENIORS trial showed that nebivolol reduced the risk of death or cardiovascular (CV) hospitalization in elderly patients with heart failure (HF). We aimed to assess tolerability and dose-related effects of the beta-blocker nebivolol in elderly patients from the SENIORS trial. METHODS: Patients assigned to nebivolol (n = 1031) were classified into 4 groups, according to the dose achieved at the end of titration phase (maintenance dose): 0 mg (n = 74), low dose (1.25 or 2.5 mg, n = 142), medium dose (5 mg, n = 127), and target dose (10 mg, n = 688) and compared with those allocated to placebo (n = 1030). Age, sex and ejection fraction were similar between the groups, but prior myocardial infarction, coronary revascularization, and serum creatinine levels were lower in patients who achieved higher maintenance doses of nebivolol. RESULTS: After adjustment, all-cause mortality or CV hospitalization was significantly reduced in the 10 mg dose group compared with placebo (hazard ratio [HR] 0.75, 95% CI 0.63-0.90) which was similar to the medium dose group (HR 0.73, 95% CI 0.52-1.02). The low dose group had an apparently lower benefit (HR 0.88, 95% CI 0.64-1.20), whereas patients unable to tolerate any dose of nebivolol had an increased risk of death or CV hospitalization (HR 1.95, 95% CI 1.38-2.75). CONCLUSIONS: The benefits of nebivolol in elderly patients with HF appear to be related to the maintenance dose achieved. Patients unable to tolerate any dose have the worst prognosis. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17584562&query_hl=1 ER - TY - JFULL T1 - Innate immunity in the pathogenesis of virus-induced asthma exacerbations. A1 - Johnston, SL J1 - Proc Am Thorac Soc Y1 - 2007/07// VL - 4 SN - 1546-3222 SP - 267 EP - 270 N2 - The major asthma morbidity, mortality, and health care costs are a result of acute exacerbations. However, exacerbations are only partially responsive to current therapies and new approaches to treatment are needed. The great majority of acute asthma exacerbations are associated with respiratory viral infections and, of viruses implicated, approximately 60% are human rhinoviruses (RVs). The mechanisms of RV-induced asthma exacerbations are poorly understood. We have previously shown that adults with asthma have increased susceptibility to naturally occurring RV infections. Our recent studies have investigated mechanisms of innate host defense against RV infection. First, primary bronchial epithelial cells from subjects with asthma were shown to replicate RV in vitro to several logs, whereas those of normal control subjects were resistant to infection. This resistance was a result of rapid induction of apoptosis and of interferon (IFN)-beta in the normal cells, whereas these responses were deficient in asthmatic cells. These studies were recently extended to a novel family of three related proteins, the IFN-lambdas 1-3, production of which was also deficient in vitro and related to asthma exacerbation severity in vivo. These studies identify novel mechanisms for the increased susceptibility of subjects with asthma to RV infection. Further studies are now required to investigate whether administration of IFN-beta or IFN-lambda may be beneficial in the treatment of asthma exacerbations, to determine whether similar deficiencies are observed in children and in subjects with nonatopic asthma, and to investigate the mechanisms of deficient IFN production in asthma to help identify better therapeutic strategies for asthma exacerbations. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17607011&query_hl=1 ER - TY - JFULL T1 - Response to mallory: you are civilized, but still wrong, dr. Mallory. A1 - Bush, A A1 - Davies, J J1 - Pediatr Pulmonol Y1 - 2007/07// VL - 42 SN - 8755-6863 SP - 658 EP - 658 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17534975&query_hl=1 ER - TY - JFULL T1 - Inflammometry and asthma: onto the next level. A1 - Bush, A J1 - Pediatr Pulmonol Y1 - 2007/07// VL - 42 SN - 8755-6863 SP - 569 EP - 572 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17526004&query_hl=1 ER - TY - JFULL T1 - Indian Asian men have less peripheral arterial disease than European men for equivalent levels of coronary disease. A1 - Chaturvedi, N A1 - Coady, E A1 - Mayet, J A1 - Wright, AR A1 - Shore, AC A1 - Byrd, S A1 - McG Thom, SA A1 - Kooner, JS A1 - Schalkwijk, CG A1 - Hughes, AD J1 - Atherosclerosis Y1 - 2007/07// VL - 193 SN - 0021-9150 SP - 204 EP - 212 N2 - OBJECTIVES: Indian Asians have high rates of heart disease and stroke, but risks of peripheral arterial disease appear to be low. This paradox, and reasons for it, have not been explored. We compared ethnic differences in peripheral arterial disease for a given level of coronary disease. METHODS: We studied 83 European and 84 Indian Asian men with a range of coronary disease. Extent of coronary atheroma was quantified by coronary artery calcification score on multislice CT. Femoral intima-media thickness (IMT) was measured by ultrasound. RESULTS: Femoral IMT was 1.58, 2.06, 2.12, and 2.69 mm in Europeans, and 0.61, 1.41, 1.81 and 2.29 in Indian Asians by increasing categories of coronary atheroma (p=0.003 for ethnic difference, adjusted for age and lumen diameter). Adjustment for smoking and systolic blood pressure, the only risk factors adversely distributed in Europeans, only partly accounted for this ethnic difference (p=0.05). Other risk factors, including lipids, obesity, insulin and glycaemic status, more adversely distributed in Indian Asians, could not account for ethnic differences. Prevalence of abnormal ankle brachial index and lower limb atherosclerotic plaque was also greater in Europeans. CONCLUSIONS: For a given level of coronary disease, Indian Asians have less lower limb atherosclerosis than Europeans, unexplained by established risk factors. Further study of these populations would help tease out relative contributions of risk factors to atherosclerosis in different vessel beds. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16860806&query_hl=1 ER - TY - JFULL T1 - Association between heat shock protein 70/Hom genetic polymorphisms and uveitis in patients with sarcoidosis. A1 - Spagnolo, P A1 - Sato, H A1 - Marshall, SE A1 - Antoniou, KM A1 - Ahmad, T A1 - Wells, AU A1 - Ahad, MA A1 - Lightman, S A1 - du Bois, RM A1 - Welsh, KI J1 - Invest Ophthalmol Vis Sci Y1 - 2007/07// VL - 48 SN - 0146-0404 SP - 3019 EP - 3025 N2 - PURPOSE: The predisposition to sarcoidosis, a systemic granulomatous disorder of unknown etiology, is genetically determined, and genetics appears also to drive the disease down distinct phenotypic pathways. This study was undertaken to test the hypothesis that sarcoidosis-related uveitis represents a genetically distinct disease subset, by investigating single nucleotide polymorphisms (SNPs) in the HSP-70/1 and HSP-70/Hom genes. HSP70 molecules play a key role in the immune response by functioning both as chaperones and as inducers of proinflammatory cytokine secretion. METHODS: By sequence-specific primers-polymerase chain reaction (SSP-PCR) five SNPs were evaluated in 270 white patients with sarcoidosis, including 88 with sarcoid-related uveitis, and in 347 matched control subjects. One hundred twenty-five patients with idiopathic anterior uveitis (IAU) and 56 with idiopathic intermediate uveitis (IIU) were also included in the study as disease control subjects. RESULTS: The HSP-70/Hom rs2075800 G allele frequency was higher in the sarcoid-uveitis group than in both the sarcoid-non-uveitis and control groups (83% vs. 71%, OR = 2.00, P(c) = 0.01; and 83% vs. 66%, OR = 2.45, P(c) = 0.00005, respectively). Similar results were observed when considering the carriage frequency of the associated haplotype (HSP-70 haplotype 2) across the three study groups (47% vs. 29%, OR = 2.17, P(c) = 0.03; and 47% vs. 21%, OR = 3.26, P(c) = 0.0003, respectively). In addition, the carriage frequency of the HSP-70 haplotype 2 discriminated among sarcoid-related uveitis, IAU, and IIU (47% vs. 19%, OR = 3.26, P(c) = 0.001; and 47% vs. 23%, OR = 2.81, P(c) = 0.04, respectively). CONCLUSIONS: A strong association was found between HSP-70/Hom rs2075800 G and uveitis in patients with sarcoidosis. Further studies are needed to understand the molecular mechanisms underlying this association. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17591867&query_hl=1 ER - TY - JFULL T1 - Heart tissue engineering using a novel elastomer and ES-derived cardiac cells A1 - Chena, QZ A1 - Wright, JS A1 - Harding, SE A1 - Junaid, S A1 - Hansen, U A1 - Jawad, H A1 - Boccaccini, AR A1 - Ali, NN J1 - TISSUE ENG Y1 - 2007/07// VL - 13 SN - 1076-3279 SP - 1703 EP - 1703 ER - TY - JFULL T1 - The prevalence, cost and basis of food allergy across Europe. A1 - Mills, EN A1 - Mackie, AR A1 - Burney, P A1 - Beyer, K A1 - Frewer, L A1 - Madsen, C A1 - Botjes, E A1 - Crevel, RW A1 - van Ree, R J1 - Allergy Y1 - 2007/07// VL - 62 SN - 0105-4538 SP - 717 EP - 722 N2 - The development of effective management strategies to optimize the quality of life for allergic patients is currently hampered by a lack of good quality information. Estimates of how many individuals suffer from food allergy and the major foods involved vary widely and inadequacies of in vitro diagnostics make food challenges the only reliable means of diagnosis in many instances. The EuroPrevall project brings together a multidisciplinary partnership to address these issues. Cohorts spanning the main climatic regions of Europe are being developed in infants through a birth cohort, community surveys in school-age children and adults and an outpatient clinic study. Confirmatory double-blind placebo-controlled food challenge diagnosis is being undertaken using foods as they are eaten with titrated doses to allow no-effect and lowest-observable effect levels for allergenic foods to be determined. The cohorts will also facilitate validation of novel in vitro diagnostics through the development of the EuroPrevall Serum Bank. Complementary studies in Ghana, western Siberia, India and China will allow us to gain insights into how different dietary patterns and exposure to microorganisms affect food allergies. New instruments to assess the socioeconomic impact of food allergy are being developed in the project and their application in the clinical cohorts will allow, for the first time, an assessment to be made of the burden this disease places on allergy sufferers and their communities. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17573717&query_hl=1 ER - TY - JFULL T1 - Predicting and evaluating response to omalizumab in patients with severe allergic asthma A1 - Bousquet, J A1 - Rabe, K A1 - Humbert, M A1 - Chung, KF A1 - Berger, W A1 - Fox, H A1 - Ayre, G A1 - Chen, H A1 - Thomas, K A1 - Blogg, M A1 - Holgate, S J1 - RESP MED Y1 - 2007/07// VL - 101 SN - 0954-6111 SP - 1483 EP - 1492 N2 - Background: Omalizumab is a monoclonal antibody indicated for treatment of severe persistent allergic asthma inadequately controlled despite optimal. controller therapy. We investigated whether patient selection could be targeted further.Methods: Data from seven randomized controlled omalizumab trials were analyzed to investigate whether pre-treatment patient baseline clinical characteristics could be identified that were predictive of a superior response to omalizumab. We also studied whether patients who respond to omalizumab following a course of treatment could be reliably identified. Univariate/multivariate analyses of INNOVATE data were performed to identify predictive baseline measures and further investigated in efficacy analyses of pooled data from seven studies. The best method of identifying responders to omalizumab following treatment was determined by assessing the ability of various clinical response criteria to identify responders and discriminate patient exacerbation and other outcomes.Results: Baseline total immunoglobulin E (IgE) was the only predictor of efficacy in INNOVATE. However, pooled analysis showed treatment benefits irrespective of IgE levels. In omalizumab-treated patients, physician's overall assessment following a course of treatment identified 61% as responders and best discriminated treatment outcomes.Conclusion: Baseline characteristics do not reliably predict benefit with omalizumab. Physician's overall assessment after 16 weeks of treatment is the most meaningful measure of response to therapy. (C) 2007 Elsevier Ltd. All rights reserved. ER - TY - JFULL T1 - Role of MRI in investigating the effects of elastic compression stockings on the deformation of the superficial and deep veins in the lower leg. A1 - Downie, SP A1 - Firmin, DN A1 - Wood, NB A1 - Thom, SA A1 - Hughes, AD A1 - Wolfe, JN A1 - Xu, XY J1 - J Magn Reson Imaging Y1 - 2007/07// VL - 26 SN - 1053-1807 SP - 80 EP - 85 N2 - PURPOSE: To evaluate the potential of MRI to investigate the mechanical effects of compression stockings on the veins of the lower limb. MATERIALS AND METHODS: The right calves of eight healthy volunteers were imaged in the prone position, with and without the presence of a compression stocking. Cross-sectional areas of all peroneal and posterior tibial veins, both saphenous veins, and any sufficiently large superficial veins were segmented in all subjects at mid-calf level in both cases. Variation in cross-sectional area along the axis of the great saphenous vein and a peroneal vein was also examined in three subjects. RESULTS: The mean cross-sectional area reduction was found to be greater in the deep veins (64%) than in the superficial veins (39%). Deep-vein cross-sections were generally elliptical, while superficial veins were approximately circular. Significant axial fluctuations were found in the cross-sectional areas. CONCLUSION: MRI offers a precise source of data on the mechanical effects of lower-limb compression. Ultrasound (US) may be more cost-effective, but the data acquired are less comprehensive. Future biomechanical studies of lower-limb compression should make use of MRI. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17659543&query_hl=1 ER - TY - JFULL T1 - Hydrodynamic evaluation of a bioreactor for tissueengineering heart valves A1 - Bowles, CT A1 - Van Loon, R A1 - Dreger, SA A1 - Biglino, G A1 - Chan, C A1 - Parker, KH A1 - Chester, AH A1 - Taylor, PM A1 - Yacoub, MH J1 - TISSUE ENG Y1 - 2007/07// VL - 13 SN - 1076-3279 SP - 1708 EP - 1708 ER - TY - JFULL T1 - Modification of biological scaffolds with specific extracellular matrix proteins enhances collagen synthesis by mesenchymal stem cells A1 - Dreger, SA A1 - Chester, AH A1 - Bowles, CT A1 - Yacoub, MH A1 - Taylor, PM J1 - TISSUE ENG Y1 - 2007/07// VL - 13 SN - 1076-3279 SP - 1729 EP - 1729 ER - TY - JFULL T1 - Exposure to substances in the workplace and new-onset asthma: an international prospective population-based study (ECRHS-II) A1 - Kogevinas, M A1 - Zock, JP A1 - Jarvis, D A1 - Kromhout, H A1 - Lillienberg, L A1 - Plana, E A1 - Radon, K A1 - Toren, K A1 - Alliksoo, A A1 - Benke, G A1 - Blanc, PD A1 - Dahlman-Hoglund, A A1 - D'Errico, A A1 - Hery, M A1 - Kennedy, S A1 - Kunzli, N A1 - Leynaert, B A1 - Mirabelli, MC A1 - Muniozguren, N A1 - Norback, D A1 - Olivieri, M A1 - Payo, F A1 - Villani, S A1 - van Sprundel, M A1 - Urrutia, I A1 - Wieslander, G A1 - Sunyer, J A1 - Anto, JM J1 - LANCET Y1 - 2007/07// VL - 370 SN - 0140-6736 SP - 336 EP - 341 N2 - Background The role of exposure to substances in the workplace in new-onset asthma is not well characterised in population-based studies. We therefore aimed to estimate the relative and attributable risks of new-onset asthma in relation to occupations, work-related exposures, and inhalation accidents.Methods We studied prospectively 6837 participants from 13 countries who previously took part in the European Community Respiratory Health Survey (1990-95) and did not report respiratory symptoms or a history of asthma at the time of the first study. Asthma was assessed by methacholine challenge test and by questionnaire data on asthma symptoms. Exposures were defined by high-risk occupations, an asthma-specific job exposure matrix with additional expert judgment, and through self-report of acute inhalation events. Relative risks for new onset asthma were calculated with log-binomial models adjusted for age, sex, smoking, and study Centre.Findings A significant excess asthma risk was seen after exposure to substances known to cause occupational asthma (Relative risk=1.6, 95% CI 1.1-2.3, p=0.017). Risks were highest for asthma defined by bronchial hyper-reactivity in addition to symptoms (2.4,1.3-4.6, p=0.008). Of common occupations, a significant excess risk of asthma was seen for nursing (2.2,1.3-4.0, p=0.007). Asthma risk was also increased in participants who reported an acute symptomatic inhalation event such as fire, mixing cleaning products, or chemical spills (RR=3.3, 95% CI 1.0-11.1, p=0.051). The population-attributable risk for adult asthma due to occupational exposures ranged from 10% to 25%, equivalent to an incidence of new-onset occupational asthma of 250-300 cases per million people per year.Interpretation Occupational exposures account for a substantial proportion of adult asthma incidence. The increased risk of asthma after inhalation accidents suggests that workers who have such accidents should be monitored closely. ER - TY - JFULL T1 - The effect of nano- and micron-sized particles of cobalt-chromium alloy on human fibroblasts in vitro. A1 - Papageorgiou, I A1 - Brown, C A1 - Schins, R A1 - Singh, S A1 - Newson, R A1 - Davis, S A1 - Fisher, J A1 - Ingham, E A1 - Case, CP J1 - Biomaterials Y1 - 2007/07// VL - 28 SN - 0142-9612 SP - 2946 EP - 2958 N2 - Wear debris from metal on polyethylene joint replacements causes asceptic loosening as a result of an inflammatory reaction of macrophages to micron-sized particles. Metal on metal implants, which generate nanoparticles, have been reintroduced into surgical practise in order to avoid this problem. There is a current concern about possible long-term effects of exposure to metal particles. In this study, the cytotoxic and genotoxic effects of nanoparticles and micron-sized particles of cobalt chrome alloy have been compared using human fibroblasts in tissue culture. Nanoparticles, which caused more free radicals in an acellular environment, induced more DNA damage than micron-sized particles using the alkaline comet assay. They induced more aneuploidy and more cytotoxicity at equivalent volumetric dose. Nanoparticles appeared to disintegrate within the cells faster than microparticles with the creation of electron dense deposits in the cell, which were enriched in cobalt. The mechanism of cell damage appears to be different after exposure to nanoparticles and microparticles. The concept of nanotoxicology is, therefore, an important consideration in the design of future surgical devices. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17379299&query_hl=1 ER - TY - JFULL T1 - Blood pressure reduction in stable angina by nifedipine was related to stroke and heart failure reduction but not to coronary interventions. A1 - Lubsen, J A1 - Vokó, Z A1 - Poole-Wilson, PA A1 - Kirwan, BA A1 - de Brouwer, S A1 - ACTION (A Coronary disease Trial Investigating Outcome with Nifedipine GITS) investigators J1 - J Clin Epidemiol Y1 - 2007/07// VL - 60 SN - 0895-4356 SP - 720 EP - 726 N2 - BACKGROUND AND OBJECTIVE: Whether blood pressure (BP) reduction is a necessary prerequisite for cardiovascular risk reduction or an epiphenomenon has not been definitively established. We used an innovative analytic method to address this question. METHODS: For 7,287 participants in a stable angina trial comparing long-acting nifedipine to placebo, we estimated the BP response after 2 weeks of treatment corrected for regression-to-the mean, and then related the latter and assigned treatment to subsequent cardiovascular outcomes. RESULTS: Subsequent stroke and heart failure was strongly related to 2-week corrected systolic BP response, but coronary angiography and bypass surgery was not. Adjustment for the 2-week corrected systolic BP response changed nifedipine effect estimates (relative to placebo) for subsequent stroke from 28% (P=0.04) to 21% (P=0.13) risk reduction, and for heart failure from 30% (P=0.02) to 21% (P=0.11) risk reduction; but did not alter the effect estimates for coronary angiography (27% reduction, P<0.001), and coronary bypass surgery (22% reduction, P=0.002). CONCLUSION: The stroke and heart failure risk reduction by nifedipine GITS in patients with stable angina can be attributed partly to its BP lowering effect, whereas effects on coronary procedures are likely to be related almost entirely to its antianginal effects. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17573988&query_hl=1 ER - TY - JFULL T1 - Force generation of different human cardiac valve interstitial cells: relevance to individual valve function and tissue engineering. A1 - Smith, S A1 - Taylor, PM A1 - Chester, AH A1 - Allen, SP A1 - Dreger, SA A1 - Eastwood, M A1 - Yacoub, MH J1 - J Heart Valve Dis Y1 - 2007/07// VL - 16 SN - 0966-8519 SP - 440 EP - 446 N2 - BACKGROUND AND AIM OF THE STUDY: Cardiac valves perform highly sophisticated functions that depend upon the specific characteristics of the component interstitial cells (ICs). The ability of valve ICs to contribute to these functions may be related to the generation of different types of tension within the valve structure. The study aim was to characterize cellular morphology and the forces generated by valve ICs and to compare this with morphology and forces generated by other cell types. METHODS: Cultured human valve ICs, pericardial fibroblasts and vascular smooth muscle cells were seeded in 3-D collagen gels and placed in a device that accurately measures the forces generated. Cell morphology was determined in seeded gels fixed in glutaraldehyde, stained with toluidine blue and visualized using a high-definition stereo light microscope. RESULTS: Valve ICs generated an average peak force of 30.9 +/- 10.4 dynes over a 24-h period which, unlike other cell types tested, increased as cell density decreased (R = 0.67, p <0.0001). The temporal pattern of force generation in mitral valve cells was significantly faster than in aortic or tricuspid cells (p <0.05). Microscopic examination revealed the formation of cellular processes establishing a cell/cell and cell/matrix network. When externally induced changes in matrix tension occurred, the valve ICs unlike the other cell types - did not respond to restore the previous level of tension. CONCLUSION: Human cardiac valve ICs produce a specific pattern of force generation that may be related to the individual function of each heart valve. The specialized function of these cells may serve as a guide for the choice of candidate cells for tissue engineering heart valves. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17702371&query_hl=1 ER - TY - JFULL T1 - Reduced systolic wave generation and increased peripheral wave reflection in chronic heart failure. A1 - Curtis, SL A1 - Zambanini, A A1 - Mayet, J A1 - McG Thom, SA A1 - Foale, R A1 - Parker, KH A1 - Hughes, AD J1 - Am J Physiol Heart Circ Physiol Y1 - 2007/07// VL - 293 SN - 0363-6135 SP - H557 EP - H562 N2 - In human heart failure the role of wave generation by the ventricle and wave reflection by the vasculature is contentious. The aim of this study was to compare wave generation and reflection in normal subjects with patients with stable compensated heart failure. Twenty-nine normal subjects and 67 patients with heart failure (New York Heart Association class II or III) were studied by noninvasive techniques applied to the common carotid artery. Data were analyzed by wave intensity analysis to determine the nature and direction of waves during the cardiac cycle. The energy carried by an early systolic forward compression wave (S wave) generated by the left ventricle and responsible for acceleration of flow in systole was significantly reduced in subjects with heart failure (P < 0.001), and the timing of the peak of this wave was delayed. In contrast, reflection of this wave was increased in subjects with heart failure (P < 0.001), but the timing of reflections with respect to the S wave was unchanged. The energy of an expansion wave generated by the heart in protodiastole was unaffected by heart failure. The carotid artery wave speed and the augmentation index did not significantly differ between subjects with heart failure compared with normal individuals. The ability of the left ventricle to generate a forward compression wave is markedly impaired in heart failure. Increased wave reflection serves to maintain systolic blood pressure but also places an additional load on cardiac function in heart failure. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17400718&query_hl=1 ER - TY - JFULL T1 - Effect of alpha 2, alpha 5 and alpha nu beta 3 integrins on mesenchymal stem cell adhesion to extracellular matrix proteins A1 - Dreger, SA A1 - Taylor, PM A1 - Yacoub, MH A1 - Chester, AH J1 - TISSUE ENG Y1 - 2007/07// VL - 13 SN - 1076-3279 SP - 1677 EP - 1678 ER - TY - JFULL T1 - Rab27b regulates mast cell granule dynamics and secretion. A1 - Mizuno, K A1 - Tolmachova, T A1 - Ushakov, DS A1 - Romao, M A1 - Abrink, M A1 - Ferenczi, MA A1 - Raposo, G A1 - Seabra, MC J1 - Traffic Y1 - 2007/07// VL - 8 SN - 1398-9219 SP - 883 EP - 892 N2 - The Rab GTPase family regulates membrane domain organization and vesicular transport pathways. Recent studies indicate that one member of the family, Rab27a, regulates transport of lysosome-related organelles in specialized cells, such as melanosomes and lytic granules. Very little is known about the related isoform, Rab27b. Here we used genetically modified mice to study the involvement of the Rab27 proteins in mast cells, which play key roles in allergic responses. Both Rab27a and Rab27b isoforms are expressed in bone marrow-derived mast cells (BMMC) and localize to secretory granules. Nevertheless, secretory defects as measured by beta-hexosaminidase release in vitro and passive cutaneous anaphylaxis in vivo were found only in Rab27b and double Rab27 knockout (KO) mice. Immunofluorescence studies suggest that a subset of Rab27b and double Rab27-deficient BMMCs exhibit mild clustering of granules. Quantitative analysis of live-cell time-lapse imaging revealed that BMMCs derived from double Rab27 KO mice showed almost 10-fold increase in granules exhibiting fast movement (>1.5 microm/s), which could be disrupted by nocodazole. These results suggest that Rab27 proteins, particularly Rab27b, play a crucial role in mast cell degranulation and that their action regulates the transition from microtubule to actin-based motility. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17587407&query_hl=1 ER - TY - JFULL T1 - Mechanisms of disease: lessons from ethnicity in the role of triglyceride metabolism in ischemic heart disease. A1 - Godsland, IF A1 - Johnston, DG A1 - Chaturvedi, N J1 - Nat Clin Pract Endocrinol Metab Y1 - 2007/07// VL - 3 SN - 1745-8374 SP - 530 EP - 538 N2 - Mean risk factor levels in various ethnic groups illustrate the potential importance of triglyceride metabolism in the risk for ischemic heart disease (IHD). Serum triglyceride concentrations are a surrogate for a range of potentially atherogenic disturbances in lipoprotein species, including increased concentrations of remnants of VLDL and chylomicron metabolism, increased small, dense LDL concentrations and reduced HDL concentrations. Differences between at-risk groups in lipoprotein profiles reflect alterations in the metabolism of triglycerides that might be greater than differences observed when only circulating triglyceride concentrations are measured. This atherogenic lipoprotein profile is typically found in association with increased visceral fat, insulin resistance and type 2 diabetes and might be a characteristic of Asian Indian ethnicity. By contrast, despite being relatively insulin resistant, Afro-Caribbean men in the UK have a low risk of IHD and lack the adverse lipoprotein profile. This could result from secretion of relatively large proportions of their VLDL as small, triglyceride-poor particles, levels of which are not augmented in response to loss of insulin action. These considerations re-endorse the potential importance of triglyceride metabolism in IHD and present opportunities for identifying useful areas in which drug targets for reducing IHD risk can be sought. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17581622&query_hl=1 ER - TY - JFULL T1 - Bronchial responsiveness in atopic adults increases with exposure to cat allergen. A1 - Chinn, S A1 - Heinrich, J A1 - Antó, JM A1 - Janson, C A1 - Norbäck, D A1 - Olivieri, M A1 - Svanes, C A1 - Sunyer, J A1 - Verlato, G A1 - Wjst, M A1 - Zock, JP A1 - Burney, PG A1 - Jarvis, DL J1 - Am J Respir Crit Care Med Y1 - 2007/07/01/ VL - 176 SN - 1073-449X SP - 20 EP - 26 N2 - Rationale: The association of asthma with sensitization and allergen exposure is known to be complex. There have been few studies of bronchial responsiveness in relation to both risk factors in adults. Objectives: To determine the relation of bronchial responsiveness to allergen exposure and IgE sensitization in a community study taking into account the major determinants of bronchial responsiveness in adulthood. Methods: Cross-sectional data were drawn from 1,884 participants in 20 centers in the European Community Respiratory Health Survey follow-up, which included measurement of house dust mite and cat allergen in mattress dust samples, and IgE sensitization to four allergens. Bronchial responsiveness to methacholine was expressed as a continuous variable, and analyzed by multiple regression. Measurements and Main Results: The trend toward greater bronchial responsiveness with increasing exposure to cat allergen was greater in those sensitized to any of the four allergens than those not sensitized (p = 0.001); there was no significant interaction between cat sensitization and Fel d 1 exposure. No trend was found with house dust mite allergen exposure. The difference in bronchial responsiveness between those exposed to the highest levels compared with the lowest was approximately -2.02 doubling doses of PD(20) (95% confidence interval, -3.06 to -0.97), and nearly as great in those exposed to more moderate levels. Conclusions: Cat allergen exposure at moderate levels may be harmful to all atopic adults. The clinical implication is that it is insufficient to test patients with asthma for cat sensitization; all atopic individuals may benefit from reduced cat exposure. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17446334&query_hl=1 ER - TY - JFULL T1 - Attenuation of ozone-induced airway inflammation and hyper-responsiveness by c-Jun NH2 terminal kinase inhibitor SP600125. A1 - Williams, AS A1 - Issa, R A1 - Leung, SY A1 - Nath, P A1 - Ferguson, GD A1 - Bennett, BL A1 - Adcock, IM A1 - Chung, KF J1 - J Pharmacol Exp Ther Y1 - 2007/07// VL - 322 SN - 0022-3565 SP - 351 EP - 359 N2 - Ozone has potent oxidizing properties, and exposure to ozone causes airway hyper-responsiveness (AHR) and lung inflammation. We determined the importance of c-Jun NH(2) terminal kinase (JNK), a member of the mitogen-activated protein kinase pathway, in ozone-induced AHR and inflammation. SP600125 [anthra[1,9-cd] pyrazol-6 (2H)-one], a specific JNK inhibitor (30 mg/kg) or vehicle, was administered by intraperitoneal injection before and after ozone exposure (3 ppm for 3 h). SP600125 significantly reduced total cells, and neutrophils in bronchoalveolar fluid recovered at 20 to 24 h after exposure and inhibited ozone-induced AHR. Ozone exposure induced activation of JNK in the lung as measured by the expression of phosphorylated-c-Jun, an effect abolished by SP600125. Gene-microarray analysis revealed that ozone increased the expression of over 400 genes by more than 2-fold, including interleukin-6 (IL-6), CXCL1 (keratinocyte cytokine), and CCL2 (monocyte chemoattractant protein-1). SP600125 modulated the expression of a subset of 29 ozone-induced genes; IL-6 and CCL2 expression were further increased, whereas the expression of metallothionein 1, hemopexin, and mitogen-activated 3 kinase 6 was decreased in SP600125-treated ozone-exposed mice. Changes in mRNA for IL-6, CXCL1, and CCL2 were confirmed by real-time polymerase chain reaction. Ozone also decreased the expression of over 500 genes, with the most potent effect on angiopoietin-1. SP600125 modulated the expression of 15 of these genes, and in particular, SP600125 reversed ozone-induced decrease in expression of the redox-sensitive transcription factor, hypoxia-induced factor-1alpha. This study highlights an important role for JNK in response to oxidative stress through modulation of specific inflammatory and redox mediators. Inhibition of JNK with small molecule kinase inhibitors may be a means of reducing ozone-induced inflammation and AHR. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17460151&query_hl=1 ER - TY - JFULL T1 - Filaggrin mutations in children with severe atopic dermatitis. A1 - Morar, N A1 - Cookson, WO A1 - Harper, JI A1 - Moffatt, MF J1 - J Invest Dermatol Y1 - 2007/07// VL - 127 SN - 1523-1747 SP - 1667 EP - 1672 N2 - Atopic dermatitis (AD) results from strong genetic and environmental interactions. AD shows genetic linkage to Chromosome 1q21. This region contains the epidermal differentiation complex (EDC), which consists of genes that form essential components of epidermal surfaces. Filaggrin (FLG) is one of these. Mutations in FLG/(R501X and 2282del4) are reported to be strongly associated with AD and to influence asthma accompanying AD. We investigated these effects in families recruited through a child with severe AD. We genotyped two panels of families, totalling 426, containing 990 affected and unaffected children. We found significant associations with AD (P=0.0001), asthma (P=0.006), and atopy (P=0.002). The FLG mutations were present in 26.7% of patients with AD, but were also present in 14.4% of children without AD. They were weakly associated with disease severity. The variants were not independently associated with asthma. The overall LOD score for genetic linkage of markers to the region was 3.57. This fell to 2.03 after accounting for the FLG mutations, indicating the presence of other genetic variants influencing AD at this locus. Our results provide further confirmation of the importance of mutations in FLG and the skin barrier in AD pathogenesis. The results indicate that investigations of other genes within the EDC should be undertaken. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17301831&query_hl=1 ER - TY - JFULL T1 - Drug effects on the mechanical properties of large arteries in humans A1 - Hope, SA A1 - Hughes, AD J1 - CLIN EXP PHARMACOL P Y1 - 2007/07// VL - 34 SN - 0305-1870 SP - 688 EP - 693 N2 - 1. Arteries become stiffer with increasing age and various disease states. A complete description of arterial mechanical properties in vivo is not possible, although a number of methods have been used.2. Detailed discussion in the present review is limited to pulse wave velocity and estimates of central waveform morphology derived by the application of a generalized arterial transfer function.3. Many drugs affect these parameters, either increasing or decreasing apparent stiffness. However, the extent to which changes reflect changes in blood pressure rather than more fundamental vessel wall properties remains unclear. Similarly, it is as yet unknown whether determining the need for, or assessing the effectiveness of, drug treatment by the assessment of arterial mechanical properties will offer any advantage and the usefulness of these techniques as routine clinical tools remains to be established. ER - TY - JFULL T1 - Patients who have dilated cardiomyopathy must have a trial of bridge to recovery: the case against that proposition. A1 - Poole-Wilson, PA J1 - Heart Fail Clin Y1 - 2007/07// VL - 3 SN - 1551-7136 SP - 317 EP - 319 N2 - The idea that patients who have dilated cardiomyopathy (presumably a large heart with near-normal coronary arteries) must have a trial of bridge to recovery is risible. Many such patients should be managed so that they go directly to transplantation and others may be better treated with drug therapy. Some may be more suited to destination therapy. What is needed in this field is more precise terminology, clearer statements of clinical intent at the time of device insertion, improved characterization of patients, more accurate clinical assessment, and above all more information from randomized clinical trials. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17723939&query_hl=1 ER - TY - JFULL T1 - Midterm experience with the Jarvik 2000 axial flow left ventricular assist device. A1 - Haj-Yahia, S A1 - Birks, EJ A1 - Rogers, P A1 - Bowles, C A1 - Hipkins, M A1 - George, R A1 - Amrani, M A1 - Petrou, M A1 - Pepper, J A1 - Dreyfus, G A1 - Khaghani, A J1 - J Thorac Cardiovasc Surg Y1 - 2007/07// VL - 134 SN - 1097-685X SP - 199 EP - 203 N2 - OBJECTIVE: Rotary axial flow pumps have several potential advantages and disadvantages over pulsatile pumps. The Jarvik 2000 is distinctive in being intracardiac. We report our experience in 22 patients. METHODS: The Jarvik 2000 was implanted in 15 men and 7 women. Mean age was 38.8 (range 23-59) years, preoperative diagnosis was dilated cardiomyopathy in 16, postpartum cardiomyopathy in 3, ischemic heart disease in 2, and chronic allograft failure in 1. Twenty-one patients were in New York Heart Association class IV, and 1 patient was in class III. Nineteen patients were on inotropic support, 6 were supported with an intra-aortic balloon pump, and 2 patients had been salvaged with a Centrimag (Levitronix) ventricular assist device. The median pulmonary vascular resistance was 3 Wood units; median pulmonary capillary wedge pressure was 26.6 mm Hg; and mean Cardiac Index was 1.5 L/min/m2. RESULTS: There were 2 early deaths and 6 late deaths. The average postoperative ventilation time and Intensive Treatment Unit stay was 2.2 and 10 days, respectively. One patient required a right ventricular assist device for short-term support and another for medium-term support. Seven patients were bridged to transplant, 3 had myocardial recovery, and 4 are ongoing. Mean and total duration of support was 280.5 and 6172 days, respectively. Driveline failures were noted in 3, but there were no pump infections or failure. CONCLUSION: The Jarvik 2000 provides satisfactory intermediate-term results as a bridge to transplant or recovery. It appears to be associated with a low rate of serious driveline or pump infections and technical failure. However, bleeding complications due to the required anticoagulation treatment frequently occurred. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17599509&query_hl=1 ER - TY - JFULL T1 - Loss of control of asthma following inhaled corticosteroid withdrawal is associated with increased sputum interleukin-8 and neutrophils. A1 - Maneechotesuwan, K A1 - Essilfie-Quaye, S A1 - Kharitonov, SA A1 - Adcock, IM A1 - Barnes, PJ J1 - Chest Y1 - 2007/07// VL - 132 SN - 0012-3692 SP - 98 EP - 105 N2 - BACKGROUND: The role of neutrophils in exacerbations of asthma is poorly understood. We examined the effect of withdrawal of inhaled corticosteroids on sputum inflammatory indexes in a double-blind study in patients with moderate, stable asthma. METHODS: Following a 2-week run in period, 24 subjects were randomized to receive either budesonide (400 microg bid) or placebo, and the study was continued for another 10 weeks. RESULTS: Loss of asthma control developed in 8 of 12 patients over the 10-week period of steroid withdrawal, whereas only 1 of 10 patients with budesonide treatment had exacerbations. Those with an exacerbation had increased sputum interleukin (IL)-8 (p < 0.0001) and increased sputum neutrophil numbers (p < 0.0001) compared to those without an exacerbation. The significant elevation in sputum IL-8 and neutrophil counts initially occurred 2 weeks prior to an exacerbation. Sputum neutrophilia correlated positively with changes in IL-8 levels (r(2) = 0.76, p = 0.01). CONCLUSIONS: Rapid withdrawal of inhaled corticosteroids results in an exacerbation of asthma that is preceded by an increase in sputum neutrophils and IL-8 concentrations, in contrast to an increase in eosinophils reported in previous studies in which inhaled steroids are slowly tapered. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17550933&query_hl=1 ER - TY - JFULL T1 - Antioxidant Properties of the Internal Thoracic Artery and the Radial Artery. A1 - Mangoush, O A1 - Athanasiou, T A1 - Nakamura, K A1 - Johnson, P A1 - Smoienski, R A1 - Sarathchandra, P A1 - Oury, T A1 - Chester, AH A1 - Amrani, M J1 - Heart Lung Circ Y1 - 2007/06/29/ SN - 1443-9506 N2 - BACKGROUND: The antioxidant properties of blood vessels contribute to their performance and patency of that vessel when used as a bypass conduit. Despite increased use of the radial artery (RA) in recent years, very little is known about its antioxidant properties. We compared the ability of the RA to generate superoxide and assessed its antioxidant protective capacity with that of the internal thoracic artery (ITA). METHODS: Vascular segments of the ITA and the RA were obtained from patients undergoing coronary artery bypass grafting (CABG) incubated in culture media for 2, 24, 48 and 72 hours. The amount of superoxide generated by each artery, and the deterioration of the endothelial function were assessed by using chemiluminescence (CL) and organ bath techniques. We also assessed the expression, localisation and the activity of superoxide dismutase (SOD) in both arteries; using reverse transcription-polymerase chain reaction (RT-PCR), immunolocalisation techniques and standard biochemical assessment of SOD activity. RESULTS: Under stress, the RA generated more superoxide (133.6+/-54.7 at 72h vs. 16.8+/-6.4 at 2h; P<0.01) and its endothelial function deteriorated faster (56.3+/-7.3 at 72h vs. 20.2+/-1.5 at 2h; P<0.0001) than that of ITA. Cu/Zn-SOD was found to be prevalent in the endothelium, while Ec-SOD was distributed evenly in the endothelium and media of both arteries. The activity of SOD was less in the RA compared with that of the ITA (510.2+/-219.8 vs. 808.6+/-343.7, respectively; P=0.03). CONCLUSIONS: Our study shows that the RA is less equipped with an antioxidant protective mechanism compared with the ITA. These findings could partially explain the differential clinical performance of these conduits in CABG. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17604222&query_hl=1 ER - TY - JFULL T1 - Sendai virus-mediated CFTR gene transfer to the airway epithelium. A1 - Ferrari, S A1 - Griesenbach, U A1 - Iida, A A1 - Farley, R A1 - Wright, AM A1 - Zhu, J A1 - Munkonge, FM A1 - Smith, SN A1 - You, J A1 - Ban, H A1 - Inoue, M A1 - Chan, M A1 - Singh, C A1 - Verdon, B A1 - Argent, BE A1 - Wainwright, B A1 - Jeffery, PK A1 - Geddes, DM A1 - Porteous, DJ A1 - Hyde, SC A1 - Gray, MA A1 - Hasegawa, M A1 - Alton, EW J1 - Gene Ther Y1 - 2007/06/28/ SN - 0969-7128 N2 - The potential for gene therapy to be an effective treatment for cystic fibrosis has been hampered by the limited gene transfer efficiency of current vectors. We have shown that recombinant Sendai virus (SeV) is highly efficient in mediating gene transfer to differentiated airway epithelial cells, because of its capacity to overcome the intra- and extracellular barriers known to limit gene delivery. Here, we have identified a novel method to allow the cystic fibrosis transmembrane conductance regulator (CFTR) cDNA sequence to be inserted within SeV (SeV-CFTR). Following in vitro transduction with SeV-CFTR, a chloride-selective current was observed using whole-cell and single-channel patch-clamp techniques. SeV-CFTR administration to the nasal epithelium of cystic fibrosis (CF) mice (Cftr(G551D) and Cftr(tm1Unc)TgN(FABPCFTR)#Jaw mice) led to partial correction of the CF chloride transport defect. In addition, when compared to a SeV control vector, a higher degree of inflammation and epithelial damage was found in the nasal epithelium of mice treated with SeV-CFTR. Second-generation transmission-incompetent F-deleted SeV-CFTR led to similar correction of the CF chloride transport defect in vivo as first-generation transmission-competent vectors. Further modifications to the vector or the host may make it easier to translate these studies into clinical trials of cystic fibrosis.Gene Therapy advance online publication, 28 June 2007; doi:10.1038/sj.gt.3302991. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17597790&query_hl=1 ER - TY - JFULL T1 - Radiofrequency Ablation of Infarct Scar-Related Ventricular Tachycardia: Correlation of Electroanatomical Data with Post-Mortem Histology. A1 - Koa-Wing, M A1 - Yen Ho, S A1 - Kojodjojo, P A1 - Peters, NS A1 - Davies, DW A1 - Kanagaratnam, P J1 - J Cardiovasc Electrophysiol Y1 - 2007/06/25/ SN - 1540-8167 N2 - Introduction: Histological data after VT ablation in humans is rare. We present a case of a patient who had ablation for VT storm and who died remotely from non-arrhythmic causes. Methods and Results: A 69-year-old male with ischemic cardiomyopathy and a dual-chamber implantable cardioverter defibrillator (ICD) presented with VT storm and multiple ICD therapies. A voltage map of the left-ventricular (LV) scar was created using CARTOtrade mark. VT was induced. An isochronal map identified the VT exit site at the scar border. No diastolic potentials were seen in this territory, so VT exit site ablation was performed, as well as at a putative entry site. VT cycle length and morphology changed during ablation, but termination only occurred with burst pacing. Post-ablation, the patient had no further shocks. He died seven months later from acute pancreatitis. The two ablation sites were identified on the post-mortem heart and used to correlate with the electroanatomical map. Scar area correlated well, measuring approximately 58.4 cm(2) macroscopically and 63.3 cm(2) on the electroanatomical map. Histology at VT exit site demonstrated areas of viable epicardial myocardium, suggesting that the circuit was at the epicardial scar border, which would explain the lack of diastolic potentials. Ablation scar did not reach the epicardium and therefore, ablation may have modified the exit site without complete interruption of the VT circuit. Conclusions: In this case, ablation was unable to terminate the VT due to failure to reach the epicardium, but was sufficient to modify the tachycardia, thereby reducing ICD therapy. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17593229&query_hl=1 ER - TY - JFULL T1 - Direct effects of apelin on cardiomyocyte contractility and electrophysiology. A1 - Farkasfalvi, K A1 - Stagg, MA A1 - Coppen, SR A1 - Siedlecka, U A1 - Lee, J A1 - Soppa, GK A1 - Marczin, N A1 - Szokodi, I A1 - Yacoub, MH A1 - Terracciano, CM J1 - Biochem Biophys Res Commun Y1 - 2007/06/15/ VL - 357 SN - 0006-291X SP - 889 EP - 895 N2 - Apelin, the ligand for the angiotensin receptor like-1, has been implicated in the pathogenesis of atrial fibrillation and heart failure. However, it is unknown if apelin has direct effects on cardiomyocyte contractility and electrophysiology. APJ-like immunoreactivity was localized to T-tubules and intercalated disc area in isolated adult rat ventricular myocytes. Apelin (1 nM) significantly increased sarcomere shortening in normal as well as failing cardiomyocytes. The transient increase in shortening was not accompanied by increased [Ca(2+)] transient amplitude. Apelin significantly activated the sarcolemmal Na(+)/H(+) exchanger (NHE) and increased intracellular pH. Moreover, apelin (10 nM) increased conduction velocity in monolayers of cultured neonatal rat cardiac myocytes. Our results demonstrate for the first time that apelin has direct effects on the propagation of action potential and contractility in cardiomyocytes. One of the mechanisms involved in the inotropic effect may be an increased myofilament sensitivity to Ca(2+) as apelin enhanced the activity of NHE with consequent intracellular alkalinization. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17466269&query_hl=1 ER - TY - JFULL T1 - Th2-driven, allergen-induced airway inflammation is reduced after treatment with anti-Tim-3 antibody in vivo. A1 - Kearley, J A1 - McMillan, SJ A1 - Lloyd, CM J1 - J Exp Med Y1 - 2007/06/11/ VL - 204 SN - 0022-1007 SP - 1289 EP - 1294 N2 - T cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3) is a surface molecule that is preferentially expressed on activated Th1 cells in comparison to Th2 cells. Blockade of Tim-3 has been shown to enhance Th1-driven pathology in vivo, suggesting that blockade of Tim-3 may improve the development of Th2-associated responses such as allergy. To examine the effects of Tim-3 blockade on the Th2 response in vivo, we administered anti-Tim-3 antibody during pulmonary inflammation induced by transfer of ovalbumin (OVA)-reactive Th2 cells, and subsequent aerosol challenge with OVA. In this model, anti-Tim-3 antibody treatment before each airway challenge significantly reduced airway hyperreactivity, with a concomitant decrease in eosinophils and Th2 cells in the lung. We examined Th1 and Th2 cytokine levels in the lung after allergen challenge and found that pulmonary expression of the Th2 cytokine IL-5 was significantly reduced, whereas IFN-gamma levels were significantly increased by anti-Tim-3 antibody treatment. Thus, blocking Tim-3 function has a beneficial effect during pulmonary inflammation by skewing the Th2 response toward that of a Th1 type, suggesting an important role for Tim-3 in the regulation of allergic disease. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17517968&query_hl=1 ER - TY - JFULL T1 - Laminar shear stress acts as a switch to regulate divergent functions of NF-{kappa}B in endothelial cells. A1 - Partridge, J A1 - Carlsen, H A1 - Enesa, K A1 - Chaudhury, H A1 - Zakkar, M A1 - Luong, L A1 - Kinderlerer, A A1 - Johns, M A1 - Blomhoff, R A1 - Mason, JC A1 - Haskard, DO A1 - Evans, PC J1 - FASEB J Y1 - 2007/06/08/ SN - 1530-6860 N2 - Regions of the arterial tree exposed to laminar flow, which exerts high shear stress, are protected from inflammation, endothelial cell (EC) death and atherosclerosis. TNFalpha activates NF-kappaB transcription factors, which potentially exert dual functions by inducing both proinflammatory and cytoprotective transcripts. We assessed whether laminar shear stress protects EC by modulating NF-kappaB function. Human umbilical vein EC (HUVEC) were cultured under shear stress (12 dynes/cm(2) for 16 h) using a parallel-plate flow chamber or were maintained in static conditions. Comparative real-time PCR revealed that preshearing significantly alters transcriptional responses to TNFalpha by enhancing the expression of cytoprotective molecules (Bcl-2, MnSOD, GADD45beta, A1) and suppressing proinflammatory transcripts (E-selectin, VCAM-1, IL-8). We demonstrated using assays of nuclear localization, NF-kappaB subunit phosphorylation, DNA-binding, and transcriptional activity that NF-kappaB is activated by TNFalpha in presheared HUVEC. Furthermore, a specific inhibitor revealed that NF-kappaB is essential for the induction of cytoprotective transcripts in presheared EC. Finally, we observed that NF-kappaB can be activated in vascular endothelium exposed to laminar shear stress in NF-kappaB-luciferase reporter mice, thus validating our cell culture experiments. We conclude that shear stress primes EC for enhanced NF-kappaB-dependent cytoprotective responsiveness while attenuating proinflammatory activation. Thus modulation of NF-kappaB function may underlie the atheroprotective effects of laminar shear stress.--Partridge, J., Carlsen, H., Enesa, K., Chaudhury, H., Zakkar, M., Luong, L., Kinderlerer, A., Johns, M., Blomhoff, R., Mason, J. C., Haskard, D. O., Evans, P. C. Laminar shear stress acts as a switch to regulate divergent functions of NF-kappaB in endothelial cells. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17557931&query_hl=1 ER - TY - JFULL T1 - IDENTIFICATION AND CHARACTERIZATION OF A DYSFUNCTIONAL CARDIAC MYOCYTE PHENOTYPE: ROLE OF BACTERIA, TOLL-LIKE RECEPTORS, AND ENDOTHELIN. A1 - Patel, TA A1 - Harding, SE A1 - Belcher, E A1 - Warner, TD A1 - Mitchell, JA J1 - Shock Y1 - 2007/06/07/ SN - 1073-2322 N2 - Cardiac myocyte dysfunction is clearly identified as underlying the acute heart failure associated with bacterial infection, as well as the chronic syndrome following cardiac damage, but the mechanisms leading to dysfunction in each case are not fully established. It is thought that local hormones such as endothelin 1 (ET-1) can increase the risk of heart failure in acute or chronic conditions. In the current study, we characterize myocytes as populations and identify a novel phenotype of the ventricular cardiac myocyte that does not contract appropriately on electrical stimulation. The noncontractile cardiac myocytes were viable and had normal calcium transients. The proportion of noncontractile cardiac myocytes was increased by bacteria (gram-positive Staphylococcus aureus or gram-negative Escherichia coli). Using selective ligands or myocytes from genetically modified mice, we established that the effects of S. aureus were mediated by Toll-like receptor 2/6 and of E. coli by Toll-like receptor 4. The transition to the noncontractile phenotype was strongly inhibited by ETA antagonism but unaffected by inhibition of NOS, suggesting that ET-1 and not NO mediates this phenomenon. These results are the first to describe the characteristics of this noncontractile phenotype and the mechanisms of its induction by bacteria. Description of the myocyte population, instead of effects only on individual cells, will be more relevant to the prediction of the depression of cardiac function. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17558348&query_hl=1 ER - TY - JFULL T1 - Z-scores of the fetal aortic isthmus and duct: an aid to assessing arch hypoplasia. A1 - Pasquini, L A1 - Mellander, M A1 - Seale, A A1 - Matsui, H A1 - Roughton, M A1 - Ho, SY A1 - Gardiner, HM J1 - Ultrasound Obstet Gynecol Y1 - 2007/06// VL - 29 SN - 0960-7692 SP - 628 EP - 633 N2 - OBJECTIVE: Prenatal diagnosis of isolated coarctation of the aorta suffers from high false positive and false negative rates. The aim of our study was to develop Z-scores for the aortic isthmus in normal fetuses as a reference for fetuses with suspected coarctation. METHODS: The aortic isthmal diameter, immediately proximal to the insertion of the arterial duct, was measured prospectively in the transverse (three vessel and trachea) and sagittal views in 221 normal fetuses at 18 to 37 weeks' gestation. The ductal diameter was measured immediately before it entered the descending aorta in the same view. All measurements were repeated three times by a single investigator and averaged. A second investigator re-measured the images of 50 cases to assess interobserver variability. Z-scores were created relating isthmal and ductal diameters to femur length and gestational age. The ratio between the isthmal and ductal diameters was calculated. RESULTS: The formula used to calculate Z-scores for the three diameters was: [ln(measured isthmal diameter) - (m ln(femur length or gestational age) + c)]/root MSE, where c is the intercept, m is a multiplier and MSE is the mean squared error. The ratio between isthmal and ductal diameters was close to a constant value of 1 (95% CI 0.97-1.01), regardless of the value of femur length or gestational age. CONCLUSION: We have defined Z-scores for the fetal aortic isthmus and arterial duct measured in the three vessels and trachea view and for the isthmus in the sagittal plane. In suspected coarctation, these Z-scores and the isthmal to ductal ratio may help in longitudinal assessment of the aortic arch and aid in the prenatal diagnosis of coarctation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17476706&query_hl=1 ER - TY - JFULL T1 - Initial experience of catheter ablation using a novel remotely steerable catheter sheath system A1 - Koa-Wing, M A1 - Kanagaratnam, P A1 - Wallace, D A1 - Lim, P A1 - Willis, B A1 - Alton, L A1 - Aston, K A1 - Sciberras, P A1 - Kojodjojo, P A1 - Wright, M A1 - Kaba, R A1 - Peters, N A1 - Davies, D J1 - HEART Y1 - 2007/06// VL - 93 SN - 1355-6037 SP - A60 EP - A61 ER - TY - JFULL T1 - Genotoxic effects of particles of surgical cobalt chrome alloy on human cells of different age in vitro. A1 - Papageorgiou, I A1 - Yin, Z A1 - Ladon, D A1 - Baird, D A1 - Lewis, AC A1 - Sood, A A1 - Newson, R A1 - Learmonth, ID A1 - Case, CP J1 - Mutat Res Y1 - 2007/06/01/ VL - 619 SN - 0027-5107 SP - 45 EP - 58 N2 - Humans are exposed to metals from industry, the environment and from wear debris from worn orthopaedic joint replacements. Patients exposed to worn cobalt chrome hip replacements show an increase of chromosome aberrations in the bone marrow adjacent to the implant and an increase of chromosome translocations and aneuploidy in the peripheral blood. This study has tested whether particles of surgical cobalt chrome alloy are able to induce similar DNA damage and chromosome aberrations in human cells in vitro. Because increasingly young patients are receiving hip replacements it has also tested whether the response is altered at different cellular age in vitro. Primary human fibroblasts, were tested at different pre senescent population doublings (PD10 (young) and PD35 (older)) to particles of cobalt chrome alloy for up to 15 days. As in patients there was an increase of aneuploidy, chromosome translocations and DNA damage after exposure to the cobalt chrome particles in vitro. The overall level of DNA damage and numerical and structural aberrations was approximately the same in young and older cells. However, the cellular reaction to the DNA damage was different. Older cells showed a greater loss of viability and induction of senescence and a lesser rate of mitosis and cell growth than young cells. They showed less change in transcription, particularly of p38 and caspase 10 mRNA levels, than young cells. They showed more complex aneuploidy in association with unseparated or prematurely separated chromatids. This study suggests that at least part of the chromosome changes in patients with worn implants may be due to direct effects of the metal wear particles from the implant. It would be of interest to test whether the altered reaction of the human cells at different in vitro age might correspond with a different incidence of chromosome aberrations in patients at different ages. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17376492&query_hl=1 ER - TY - JFULL T1 - ERS guidelines on the assessment of cough. A1 - Morice, AH A1 - Fontana, GA A1 - Belvisi, MG A1 - Birring, SS A1 - Chung, KF A1 - Dicpinigaitis, PV A1 - Kastelik, JA A1 - McGarvey, LP A1 - Smith, JA A1 - Tatar, M A1 - Widdicombe, J A1 - European Respiratory Society (ERS) J1 - Eur Respir J Y1 - 2007/06// VL - 29 SN - 0903-1936 SP - 1256 EP - 1276 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17540788&query_hl=1 ER - TY - JFULL T1 - The critical role of ERBB2 in human left ventricular remodelling due to pressure or volume overload A1 - Jin, X A1 - Hu, J A1 - Pezzella, F A1 - Pepper, J J1 - HEART Y1 - 2007/06// VL - 93 SN - 1355-6037 SP - A18 EP - A19 ER - TY - JFULL T1 - Success and clinical outcome of catheter ablation for supraventricular tachycardia in patients with severe pulmonary hypertension without congenital heart disease: A case series report A1 - Showkathali, R A1 - Alzetani, M A1 - Grapsa, J A1 - Nihoyannopoulos, P A1 - Howard, L A1 - Lefroy, D A1 - Gibbs, J J1 - HEART Y1 - 2007/06// VL - 93 SN - 1355-6037 SP - A102 EP - A102 ER - TY - JFULL T1 - Black-blood T2* technique for myocardial iron measurement in thalassemia. A1 - He, T A1 - Gatehouse, PD A1 - Kirk, P A1 - Tanner, MA A1 - Smith, GC A1 - Keegan, J A1 - Mohiaddin, RH A1 - Pennell, DJ A1 - Firmin, DN J1 - J Magn Reson Imaging Y1 - 2007/06// VL - 25 SN - 1053-1807 SP - 1205 EP - 1209 N2 - PURPOSE: To compare the effectiveness and reproducibility of a new black-blood sequence vs. a conventional bright-blood gradient-echo T2* sequence for myocardial iron overload measurement in thalassemia. MATERIALS AND METHODS: Twenty thalassemia patients were studied. Black-blood sequence images were acquired in diastole after a double inversion recovery (DIR) preparation pulse. Bright-blood sequence images were acquired in both early systole and late diastole. The data were randomized and the T2* analysis was performed blindly by two independent observers. RESULTS: The T2* values from the black-blood sequence were comparable to those of the conventional bright-blood sequence (25.7 +/- 12.9 msec vs. 26.4 +/- 14.2 msec in early systole, P = 0.44; and 25.2 +/- 13.1 msec in late diastole, P = 0.41). The coefficient of variation (CV) for black-blood image T2* analysis was 4.1% compared with 8.9% (early systole P = 0.03) and 7.8% (late diastole P = 0.05) for bright-blood image analysis. CONCLUSION: The black-blood T2* technique yields high-contrast myocardial images, provides clearly depicted myocardial borders, and avoids blood signal contamination of the myocardium while yielding improvements in interobserver variability. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17520740&query_hl=1 ER - TY - JFULL T1 - The effects of beta(2)-adrenoceptor agonists on conduction velocity, field potentials and automaticity in cardiomyocytes A1 - Stagg, MA A1 - Patel, NG A1 - Siedlecka, U A1 - Soppa, GKR A1 - Lee, J A1 - Yacoub, MH A1 - Terracciano, CMN J1 - J MOL CELL CARDIOL Y1 - 2007/06// VL - 42 SN - 0022-2828 SP - S25 EP - S25 ER - TY - JFULL T1 - Differential effects of SERCA2a transfection on ventricular arrhythmia susceptibility in the normal rat heart A1 - Lyon, AR A1 - Poole-Wilson, PA A1 - Peters, NS A1 - Harding, SE J1 - J MOL CELL CARDIOL Y1 - 2007/06// VL - 42 SN - 0022-2828 SP - S20 EP - S20 ER - TY - JFULL T1 - Enhanced systemic no bioavailability by growth-hormone mediated IGF-1 increase improves number and function of endothelial progenitor cells in aged individuals A1 - Thum, T A1 - Hoeber, S A1 - Froese, S A1 - Klink, I A1 - Stichtenoth, DO A1 - Galuppo, P A1 - Jakob, M A1 - Tsikas, D A1 - Anker, SD A1 - Poole-Wilson, PA A1 - Ertl, G A1 - Bauersachs, J J1 - ATHEROSCLEROSIS SUPP Y1 - 2007/06// VL - 8 SN - 1567-5688 SP - 215 EP - 215 ER - TY - JFULL T1 - Randomised, double blind, placebo-controlled trial of selenium supplementation in adult asthma. A1 - Shaheen, SO A1 - Newson, RB A1 - Rayman, MP A1 - Wong, AP A1 - Tumilty, MK A1 - Phillips, JM A1 - Potts, JF A1 - Kelly, FJ A1 - White, PT A1 - Burney, PG J1 - Thorax Y1 - 2007/06// VL - 62 SN - 0040-6376 SP - 483 EP - 490 N2 - BACKGROUND: Epidemiological evidence from observational studies has suggested that blood levels and dietary intake of selenium of adults with asthma are lower than those of controls. The only previous trial of selenium supplementation in adults with asthma found no objective evidence of benefit but involved only 24 participants. METHODS: A randomised, double blind, placebo-controlled trial of selenium supplementation was performed in adults with asthma in London, UK, the majority of whom (75%) reported inhaled steroid use at baseline. 197 participants were randomised to receive either a high-selenium yeast preparation (100 microg daily, n=99) or placebo (yeast only, n=98) for 24 weeks. The primary outcome was asthma-related quality of life (QoL) score. Secondary outcomes included lung function, asthma symptom scores, peak flow and bronchodilator usage. Linear regression was used to analyse the change in outcome between the two treatment arms by "intention to treat". RESULTS: There was a 48% increase in plasma selenium between baseline and end of trial in the active treatment group but no change in the placebo group. While the QoL score improved more in the active treatment group than in the placebo group, the difference in change in score between the two groups was not significant (-0.05 (95% CI -0.19 to 0.09); p=0.47). Selenium supplementation was not associated with any significant improvement in secondary outcomes compared with placebo. CONCLUSIONS: Selenium supplementation had no clinical benefit in adults with asthma, the majority of whom were taking inhaled steroids. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17234657&query_hl=1 ER - TY - JFULL T1 - The Stent or Surgery long-term follow-up A1 - Stables, R A1 - Booth, J A1 - Pepper, J A1 - Clayton, T A1 - Flather, M A1 - Nugara, F A1 - Sigwart, U J1 - HEART Y1 - 2007/06// VL - 93 SN - 1355-6037 SP - A7 EP - A7 ER - TY - JFULL T1 - Safety and tolerability of three consecutive bronchoscopies after allergen challenge in volunteers with mild asthma. A1 - Kariyawasam, HH A1 - Aizen, M A1 - Kay, AB A1 - Robinson, DS J1 - Thorax Y1 - 2007/06// VL - 62 SN - 0040-6376 SP - 557 EP - 558 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17536034&query_hl=1 ER - TY - JFULL T1 - Regulation of the expression of ATF3 in cardiac myocytes in response to hypertrophic and apoptotic stimulation A1 - Giraldo, A A1 - Pikkarainen, S A1 - Sugden, PH A1 - Clerk, A J1 - J MOL CELL CARDIOL Y1 - 2007/06// VL - 42 SN - 0022-2828 SP - S84 EP - S84 ER - TY - JFULL T1 - Childhood asthma and fruit consumption. A1 - Okoko, BJ A1 - Burney, PG A1 - Newson, RB A1 - Potts, JF A1 - Shaheen, SO J1 - Eur Respir J Y1 - 2007/06// VL - 29 SN - 0903-1936 SP - 1161 EP - 1168 N2 - The present authors investigated whether wheezing is less common in children who consume more apples and other fruits. A population-based survey of 2,640 primary school children aged 5-10 yrs was carried out in Greenwich (South London, UK). Information about asthma symptoms and fruit consumption was obtained by means of a questionnaire. After controlling for potential confounding variables, eating bananas at least once a day (compared with less than once a month) was negatively associated with current wheeze (odds ratio 0.66; 95% confidence interval 0.44-1.00) and ever wheeze (0.69 (0.50-0.95)), but not with ever asthma (0.80 (0.56-1.14)). Drinking apple juice from concentrate at least once a day (compared with less than once a month) was also negatively associated with current wheeze (0.53 (0.34-0.83)), weakly associated with ever wheeze (0.74 (-0.54-1.02)), but not associated with ever asthma. Consumption of apples, other fruits and orange juice was not significantly associated with asthma symptoms. No association was found between eating fresh apples and asthma symptoms in the study population, but some evidence was found to suggest that a higher consumption of apple juice from concentrate and bananas may protect against wheezing in children. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17301090&query_hl=1 ER - TY - JFULL T1 - Emerging therapies for pulmonary arterial hypertension. A1 - Ali, O A1 - Wharton, J A1 - Gibbs, JS A1 - Howard, L A1 - Wilkins, MR J1 - Expert Opin Investig Drugs Y1 - 2007/06// VL - 16 SN - 1744-7658 SP - 803 EP - 818 N2 - Pulmonary arterial hypertension is characterised by increased pulmonary vascular resistance due to increased vascular tone and structural remodelling of pulmonary vessels. The therapies that are in use so far have been developed to correct endothelial dysfunction and reduce vasomotor tone. These treatments have a limited effect on the remodelling process and, increasingly, the focus is turning to potent strategies for inhibiting vascular proliferation and promoting vascular apoptosis. Multiple novel targets have been uncovered over the last 5 years and several are now in early clinical trials. At present, it is clear that there is no single treatment for the condition. Although this is the case, studies are investigating the role of combining therapies that are already established. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17501693&query_hl=1 ER - TY - JFULL T1 - Effects of transmural pressure and wall shear stress on LDL accumulation in the arterial wall: a numerical study using a multilayered model. A1 - Sun, N A1 - Wood, NB A1 - Hughes, AD A1 - Thom, SA A1 - Yun Xu, X J1 - Am J Physiol Heart Circ Physiol Y1 - 2007/06// VL - 292 SN - 0363-6135 SP - H3148 EP - H3157 N2 - The accumulation of low-density lipoprotein (LDL) is recognized as one of the main contributors in atherogenesis. Mathematical models have been constructed to simulate mass transport in large arteries and the consequent lipid accumulation in the arterial wall. The objective of this study was to investigate the influences of wall shear stress and transmural pressure on LDL accumulation in the arterial wall by a multilayered, coupled lumen-wall model. The model employs the Navier-Stokes equations and Darcy's Law for fluid dynamics, convection-diffusion-reaction equations for mass balance, and Kedem-Katchalsky equations for interfacial coupling. To determine physiologically realistic model parameters, an optimization approach that searches optimal parameters based on experimental data was developed. Two sets of model parameters corresponding to different transmural pressures were found by the optimization approach using experimental data in the literature. Furthermore, a shear-dependent hydraulic conductivity relation reported previously was adopted. The integrated multilayered model was applied to an axisymmetric stenosis simulating an idealized, mildly stenosed coronary artery. The results show that low wall shear stress leads to focal LDL accumulation by weakening the convective clearance effect of transmural flow, whereas high transmural pressure, associated with hypertension, leads to global elevation of LDL concentration in the arterial wall by facilitating the passage of LDL through wall layers. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17277019&query_hl=1 ER - TY - JFULL T1 - A unifying explanation of the arterial pulse waveform in humans and the implications for central blood pressure augmentation A1 - Davies, J A1 - Hadjiloizou, N A1 - Manisty, C A1 - Whinnett, Z A1 - Foale, R A1 - Malik, I A1 - Hughes, A A1 - Parker, K A1 - Darrel, D A1 - Mayet, J J1 - HEART Y1 - 2007/06// VL - 93 SN - 1355-6037 SP - A79 EP - A80 ER - TY - JFULL T1 - Factors affecting adherence to asthma treatment in an international cohort of young and middle-aged adults A1 - Corsico, AG A1 - Cazzoletti, L A1 - de Marco, R A1 - Janson, C A1 - Jarvis, D A1 - Zoia, MC A1 - Bugiani, M A1 - Accordini, S A1 - Villani, S A1 - Marinoni, A A1 - Gislason, D A1 - Gulsvik, A A1 - Pin, I A1 - Vermeire, P A1 - Cerveri, I J1 - RESP MED Y1 - 2007/06// VL - 101 SN - 0954-6111 SP - 1363 EP - 1367 N2 - Background: A major reason of the poor control of asthma is that patients fail to adhere to their treatment. The aim of the study was to identify factors affecting changes in asthma treatment adherence in an international cohort.Methods: A follow-up study was carried out by means of a structured clinical interview in 971 subjects with asthma from 12 countries who participated in both the European Community Respiratory Health Survey: ECRHS-I (1990-94) and ECRHS-II (1998-2002). Subjects were considered adherent if they reported they normally took all the prescribed drugs. A logistic model was used to study the adjusted effect of the determinants.Results: The net change in adherence to anti-asthmatic treatment per 10 years of follow-up was -2% (95% Cl: -9.5, 5.5), 7.5% (-2.6, 17.6), 15.0% (6.6, 23.5) and 19.8% (4.1, 35.5), respectively, in Nordic, Mediterranean, Continental and extra-European areas. Among the 428 non-adherent subjects in ECRHS-I, having regular consultations with health care professionals was the strongest predictor of increased adherence (OR 3.32; 95% CI: 1.08-10.17). Among the 543 adherent subjects in ECRHS-I, using inhaled corticosteroids significantly predicted a persistence of adherence (OR 2.04; 95% CI: 1.11-3.75). No effect of gender, age, duration of the disease, smoking habit and educational level was observed. Conclusions: Our findings highlight the key role of doctors and nurses in educating and regularly reviewing the patients and support the efforts for an improvement of clinical Communication. (c) 2006 Elsevier Ltd. AU rights reserved. ER - TY - JFULL T1 - Clenbuterol prevents G(alpha i) protein reduction induced by mechanical unloading in failing cardiomyocytes A1 - Soppa, GKR A1 - Latif, N A1 - Lee, J A1 - Stagg, MA A1 - Siedlecka, U A1 - Yacoub, MH A1 - Terracciano, CMN J1 - J MOL CELL CARDIOL Y1 - 2007/06// VL - 42 SN - 0022-2828 SP - S152 EP - S152 ER - TY - JFULL T1 - In vitro motility studies of a DCM mutation in cardiac muscle actin A1 - Dyer, E A1 - Wells, D A1 - Redwoods, C A1 - Marston, S J1 - J MOL CELL CARDIOL Y1 - 2007/06// VL - 42 SN - 0022-2828 SP - S162 EP - S162 ER - TY - JFULL T1 - Building better mouse models of asthma. A1 - Lloyd, CM J1 - Curr Allergy Asthma Rep Y1 - 2007/06// VL - 7 SN - 1529-7322 SP - 231 EP - 236 N2 - Allergic asthma is a complex disease that has been modeled extensively in small rodents. Airway eosinophilia and changes in lung function have been documented using a variety of protocols. However, recent efforts have improved these models by trying to replicate the structural remodeling that occurs in the lung as a consequence of chronic allergen-driven inflammation. This review documents the recent developments in protocols and systems designed to examine pathways leading to allergen-induced airway remodeling. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17448336&query_hl=1 ER - TY - JFULL T1 - The Clinical Assessment of Retinal Microvascular Structure and Therapeutic Implications. A1 - Hughes, AD J1 - Curr Treat Options Cardiovasc Med Y1 - 2007/06// VL - 9 SN - 1092-8464 SP - 236 EP - 241 N2 - Examination of the retinal microvasculature is widely used to assess diabetic eye disease and as an indicator of target organ damage in hypertension. The diagnostic value of grading of hypertensive retinopathy is dubious; however, many recent studies have demonstrated that hypertensive retinopathy is associated with a range of risk factors for cardiovascular disease and may predict cardiovascular events independently of blood pressure. Developments in digital imaging and computer-assisted analysis have facilitated the quantitative assessment of microvascular changes in cardiovascular disease. These approaches may be useful for assessing cardiovascular risk and targeting therapeutic intervention. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17601388&query_hl=1 ER - TY - JFULL T1 - Corticosteroid inhibition of growth-related oncogene protein-alpha via mitogen-activated kinase phosphatase-1 in airway smooth muscle cells. A1 - Issa, R A1 - Xie, S A1 - Khorasani, N A1 - Sukkar, M A1 - Adcock, IM A1 - Lee, KY A1 - Chung, KF J1 - J Immunol Y1 - 2007/06/01/ VL - 178 SN - 0022-1767 SP - 7366 EP - 7375 N2 - Expression of the inflammatory chemokine, growth-related oncogene protein-alpha (GRO-alpha), from airway smooth muscle cells (ASMC) is regulated by pathways involving NF-kappaB and MAPK activation. We determined the effects of dexamethasone on GRO-alpha induced by IL-1beta or TNF-alpha with respect to the role of MAPK pathways and of MAPK phosphatase-1 (MKP-1). Human ASMC were studied in primary culture at confluence. Dexamethasone (10(-8)-10(-5) M) partially inhibited GRO-alpha expression and release induced by IL-1beta and TNF-alpha; this was associated with an inhibition of JNK, but not of p38 or ERK phosphorylation. Together with IL-1beta or TNF-alpha, dexamethasone rapidly induced mRNA and protein expression of MKP-1, which dephosphorylates MAPKs. Using MKP-1 small interfering RNA (siRNA) to block the expression of IL-1beta- and dexamethasone-induced MKP-1 by 50%, JNK phosphorylation was doubled. The inhibitory effect of dexamethasone on GRO-alpha release was partially reversed in ASMC treated with MKP-1 siRNA compared with those treated with scrambled siRNA. In contrast, overexpression of MKP-1 led to a reduction in IL-1beta-induced release of GRO-alpha, but the inhibitory effects of dexamethasone were preserved. Nuclear translocation of the glucocorticoid receptor was increased in ASMC exposed to dexamethasone and IL-1beta. Using chromatin immunoprecipitation assay, glucocorticoid receptor binding to the MKP-1 promoter was increased by IL-1beta and dexamethasone compared with either alone. Glucocorticoids and IL-1beta or TNF-alpha modulate GRO-alpha release partly through the inhibition of JNK pathway, resulting from an up-regulation of MKP-1 expression. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17513787&query_hl=1 ER - TY - JFULL T1 - Inhibition of facilitated antigen presentation by venom immunotherapy in children A1 - Varga, E A1 - Zach, M A1 - Klunker, S A1 - Aberer, W A1 - Durham, S A1 - Francis, J J1 - ALLERGY Y1 - 2007/06// VL - 62 SN - 0105-4538 SP - 73 EP - 74 ER - TY - JFULL T1 - Optimal consultations for those with respiratory illness A1 - Roberts, NR A1 - Partridge, MR J1 - Breathe Y1 - 2007/06// IS - 4 VL - 3 PB - European Respiratory Society SP - 331 EP - 337 ER - TY - JFULL T1 - Should preschool wheezers ever be treated with inhaled corticosteroids? A1 - Saglani, S A1 - Wilson, N A1 - Bush, A J1 - Semin Respir Crit Care Med Y1 - 2007/06// VL - 28 SN - 1069-3424 SP - 272 EP - 285 N2 - The syndrome of preschool wheeze commonly regresses completely in the preschool years, but it may lead to prolonged symptoms and established asthma. Although epidemiological studies have established that there are several different phenotypes, it is currently impossible to assign the majority of wheezing preschool children to a phenotype prospectively. Bronchoalveolar lavage studies have shown an increase in total cellular inflammation in the youngest, symptomatic children, and that in older preschool children the neutrophil is the predominant inflammatory cell in the airway. Endobronchial biopsy studies have shown that eosinophilic inflammation and structural airway wall changes are absent in symptomatic infants but appear in severe wheezers by the age of 3 years. Treatment guidelines are not evidence based in this age group and frequently do not appear to consider either the likely pathology or the different patterns of symptoms. Pure virus-associated symptoms may be treated with intermittent beta-2 agonist or anticholinergics by inhalation. If this fails, intermittent oral leukotriene receptor antagonists or short courses of very high dose inhaled corticosteroids could be considered. The role of oral corticosteroids is highly debatable in young children with virus-associated wheeze. Prophylactic therapy may be considered for chronic intermittent symptoms (interval symptoms between acute episodes). The choices are oral leukotriene receptor antagonists, or inhaled corticosteroids, which should be introduced in a three-stage protocol to avoid overtreating the child with evanescent symptoms. Because the natural history of preschool wheeze is one of improvement, treatment should be tapered after a period of stability. Unfortunately, neither corticosteroids nor any other currently available therapy modifies the long-term outcome of preschool wheeze. In conclusion, corticosteroid treatment may have a small role in preschool wheeze, in particular for those thought to have early asthma, but the uncritical application of recommendations that are appropriate for older children and adults with asthma has led to widespread overuse of these medications. There is an urgent need for better treatment of preschool wheeze. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17562497&query_hl=1 ER - TY - JFULL T1 - Misleading meta-analysis: a need to look beyond the headlines. A1 - Chaturvedi, N A1 - Bilous, R A1 - Hardy, R A1 - Remuzzi, G A1 - Ruggenenti, P A1 - Viberti, GC J1 - Diabet Med Y1 - 2007/06// VL - 24 SN - 0742-3071 SP - 587 EP - 591 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17490423&query_hl=1 ER - TY - JFULL T1 - FOXP3+CD4+CD25+T regulatory cells in the nasal mucosa: influence of grass pollen immunotherapy A1 - Nouri-Aria, K A1 - Radulovic, S A1 - Jacobson, M A1 - Durham, S J1 - ALLERGY Y1 - 2007/06// VL - 62 SN - 0105-4538 SP - 72 EP - 73 ER - TY - JFULL T1 - A study of the relation between gap junction expression, conductance and conduction velocity in intact myocardium A1 - Dhillon, P A1 - Shipolini, A A1 - Tsang, V A1 - Fry, C A1 - Peters, N J1 - HEART Y1 - 2007/06// VL - 93 SN - 1355-6037 SP - A1 EP - A1 ER - TY - JFULL T1 - Fatal hypertrophic cardiornyopathy and nemaline myopathy associated with ACTA1 K336E mutation A1 - Marston, S A1 - Bertini, E A1 - Porfirio, A A1 - Graziano, C A1 - Petrini, S A1 - D'Amico, A A1 - Santorelli, FM A1 - Pacileo, G A1 - Sewry, C J1 - J MOL CELL CARDIOL Y1 - 2007/06// VL - 42 SN - 0022-2828 SP - S73 EP - S73 ER - TY - JFULL T1 - Differences in the magnitude rather than the timing of wave reflection can explain the ASCOT results A1 - Manisty, C A1 - Davies, J A1 - Whinnett, Z A1 - Francis, D A1 - Zambanini, A A1 - Zambanini, A A1 - Curtis, S A1 - Thom, S A1 - Hughes, A A1 - Mayet, J J1 - HEART Y1 - 2007/06// VL - 93 SN - 1355-6037 SP - A80 EP - A80 ER - TY - JFULL T1 - Novel observation of regions of highly organised activation and stable frequency during chronic atrial fibrillation in the human left atrium: Do they represent fixed drivers? A1 - Jarman, J A1 - Wong, T A1 - Spohr, H A1 - Kojodjojo, P A1 - Davies, J A1 - Segal, O A1 - Francis, D A1 - Davies, D A1 - Markides, V A1 - Peters, N J1 - HEART Y1 - 2007/06// VL - 93 SN - 1355-6037 SP - A3 EP - A3 ER - TY - JFULL T1 - Responses to endothelin in human embryonic stem cell-derived cardiomyocytes A1 - Wright, J A1 - Ahmet, S A1 - Harding, SE A1 - Ali, NN J1 - J MOL CELL CARDIOL Y1 - 2007/06// VL - 42 SN - 0022-2828 SP - S88 EP - S88 ER - TY - JFULL T1 - Coronary heart disease patients' perception of their symptoms and sense of control before hospital discharge predicts their quality of life in the long term A1 - Lau-Walker, M A1 - Cowie, M J1 - HEART Y1 - 2007/06// VL - 93 SN - 1355-6037 SP - A28 EP - A28 ER - TY - JFULL T1 - Sublingual grass tablet immunotherapy shows a progressive immunological effect A1 - Kapp, A A1 - Rak, S A1 - de Monchy, J A1 - Emminger, W A1 - Colombo, G A1 - Dahl, R A1 - Gronager, P A1 - Henmar, H A1 - Durham, S J1 - ALLERGY Y1 - 2007/06// VL - 62 SN - 0105-4538 SP - 238 EP - 238 ER - TY - JFULL T1 - MRI tracking of systemically administered bone marrow stem cells A1 - Carr, CA A1 - Stuckey, DJ A1 - Tatton, L A1 - Tyler, DJ A1 - Harding, SE A1 - Clarke, K J1 - J MOL CELL CARDIOL Y1 - 2007/06// VL - 42 SN - 0022-2828 SP - S88 EP - S89 ER - TY - JFULL T1 - A novel Z-groove index characterizing myocardial surface structure and its modification in failing human heart A1 - Gorelik, J A1 - Yang, L A1 - Zhang, Y A1 - Lab, M A1 - Korcbev, YE A1 - del Monte, F A1 - Harding, SE J1 - J MOL CELL CARDIOL Y1 - 2007/06// VL - 42 SN - 0022-2828 SP - S153 EP - S153 ER - TY - JFULL T1 - Clenbuterol affects rat ventricular myocyie contractility via an inhibitory G protein-mediated pathway A1 - Siedlecka, U A1 - Arora, M A1 - Soppa, GKR A1 - Lee, J A1 - Stagg, MA A1 - Harding, SE A1 - Yacoub, MH A1 - Terracciano, CMN J1 - J MOL CELL CARDIOL Y1 - 2007/06// VL - 42 SN - 0022-2828 SP - S49 EP - S49 ER - TY - JFULL T1 - Age-related changes in carotid artery lumen and wall volume in a population free of cardiac risk factors A1 - Keenan, N A1 - Pennell, D J1 - HEART Y1 - 2007/06// VL - 93 SN - 1355-6037 SP - A91 EP - A92 ER - TY - JFULL T1 - Glucose control in the critically ill-still so many questions. A1 - Finney, SJ J1 - J Crit Care Y1 - 2007/06// VL - 22 SN - 0883-9441 SP - 118 EP - 119 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17548022&query_hl=1 ER - TY - JFULL T1 - Health effects of nanomaterials. A1 - Tetley, TD J1 - Biochem Soc Trans Y1 - 2007/06// VL - 35 SN - 0300-5127 SP - 527 EP - 531 N2 - With the rapid growth of nanotechnology and future bulk manufacture of nanomaterials comes the need to determine, understand and counteract any adverse health effects of these materials that may occur during manufacture, during use, or accidentally. Nanotechnology is expanding rapidly and will affect many aspects of everyday life; there are already hundreds of products that utilize nanoparticles. Paradoxically, the unique properties that are being exploited (e.g. high surface reactivity and ability to cross cell membranes) might have negative health impacts. The rapid progress in development and use of nanomaterials is not yet matched by toxicological investigations. Epidemiological studies implicate the ultrafine (nano-sized) fraction of particulate air pollution in the exacerbation of cardiorespiratory disease and increased morbidity. Experimental animal studies suggest that the increased concentration of nanoparticles and higher reactive surface area per unit mass, alongside unique chemistry and functionality, is important in the acute inflammatory and chronic response. Some animal models have shown that nanoparticles which are deposited in one organ (e.g. lung and gut) may access the vasculature and target other organs (e.g. brain and liver). The exact relationship between the physicochemistry of a nanoparticle, its cellular reactivity, and its biological and systemic consequences cannot be predicted. It is important to understand such relationships to enjoy the benefits of nanotechnology without being exposed to the hazards. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17511644&query_hl=1 ER - TY - JFULL T1 - Phosphodiesterase activity in isolated cardiomyocytes from rat, guinea pig and human heart A1 - Johnson, WB A1 - Katugampola, S A1 - Napier, C A1 - Harding, SE J1 - J MOL CELL CARDIOL Y1 - 2007/06// VL - 42 SN - 0022-2828 SP - S116 EP - S116 ER - TY - JFULL T1 - The role of moderate alcohol intake in first detected atrial fibrillation: The imperial college new AF study A1 - Martins, J A1 - Fox, K A1 - Wood, D A1 - Lefroy, D A1 - Collier, T A1 - Peters, N J1 - HEART Y1 - 2007/06// VL - 93 SN - 1355-6037 SP - A31 EP - A31 ER - TY - JFULL T1 - Progressive myocardial scarring from sarcoidosis. A1 - Silva, C A1 - Moon, JC A1 - Pennell, DJ J1 - J Cardiovasc Med (Hagerstown) Y1 - 2007/06// VL - 8 SN - 1558-2027 SP - 468 EP - 469 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17502767&query_hl=1 ER - TY - JFULL T1 - The combination of anti-IgE monoclonal antibody (omalizumab) with ragweed immunotherapy results in enhanced and long-term inhibitory effects on facilitated-antigen presentation A1 - James, F A1 - Saggar, L A1 - Klunker, S A1 - Seyfert-Margolis, V A1 - Asare, A A1 - Casale, T A1 - Durham, S A1 - Immune Tolerance Network Grp J1 - ALLERGY Y1 - 2007/06// VL - 62 SN - 0105-4538 SP - 61 EP - 61 ER - TY - JFULL T1 - Physiological evidence of the "second factor" in atrial remodelling is accompanied by localised conduction abnormalities in the chronic goat model of atrial fibrillation A1 - Kirubakaran, S A1 - Hall, M A1 - Peters, N A1 - Garratt, C J1 - HEART Y1 - 2007/06// VL - 93 SN - 1355-6037 SP - A55 EP - A56 ER - TY - JFULL T1 - Emerging and unusual gram-negative infections in cystic fibrosis. A1 - Davies, JC A1 - Rubin, BK J1 - Semin Respir Crit Care Med Y1 - 2007/06// VL - 28 SN - 1069-3424 SP - 312 EP - 321 N2 - People with cystic fibrosis (CF) have chronic airway infection and frequent exposure to antibiotics, which often leads to the emergence of resistant organisms. In addition to the development of multiresistance in common CF pathogens such as Pseudomonas aeruginosa, several newer, inherently resistant gram-negative species are becoming more common, including Burkholderia cepacia complex, Stenotrophomonas maltophilia, Achromobacter (Alcaligenes) xylosoxidans, certain Ralstonia species, and those within the new genus Pandoraea. Many of these are closely related and have similar phenotypes, making accurate laboratory identification challenging. Although their role in contributing to pulmonary disease in CF is not clear, some, such as those of the B. cepacia complex, are clearly linked to an adverse prognosis, and both treatment and infection control issues can pose a real challenge. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17562501&query_hl=1 ER - TY - JFULL T1 - Critical role of toll-like receptors and nucleotide oligomerisation domain in the regulation of health and disease. A1 - Mitchell, JA A1 - Paul-Clark, MJ A1 - Clarke, GW A1 - McMaster, SK A1 - Cartwright, N J1 - J Endocrinol Y1 - 2007/06// VL - 193 SN - 0022-0795 SP - 323 EP - 330 N2 - Pathogens are sensed by pattern recognition receptors (PRRs), which are germ line-encoded receptors, including transmembrane Toll-like receptors (TLRs) and cytosolic nucleotide oligomerisation domain (NOD) proteins, containing leucine-rich repeats (NLRs). Activation of PRRs by specific pathogen-associated molecular patterns (PAMPs) results in genomic responses in host cells involving activation transcription factors and the induction of genes. There are now at least 10 TLRs in humans and 13 in mice, and 2 NLRs (NOD1 and NOD2). TLR signalling is via interactions with adaptor proteins including MyD88 and toll-receptor associated activator of interferon (TRIF). NOD signalling is via the inflammasome and involves activation of Rip-like interactive clarp kinase (RICK). Bacterial lipopolysaccharide (LPS) from Gram-negative bacteria is the best-studied PAMP and is activated by or 'sensed' by TLR4. Lipoteichoic acid (LTA) from Gram-positive bacteria is sensed by TLR2. TLR4 and TLR2 have different signalling cascades, although activation of either results in symptoms of sepsis and shock. This review describes the rapidly expanding field of pathogen-sensing receptors and uses LPS and LTA as examples of how these pathways parallel and diverge from each other. The role of pathogen-sensing pathways in disease is also discussed. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17535871&query_hl=1 ER - TY - JFULL T1 - Invited commentary. A1 - Pepper, JR J1 - Ann Thorac Surg Y1 - 2007/06// VL - 83 SN - 1552-6259 SP - 2058 EP - 2059 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17532396&query_hl=1 ER - TY - JFULL T1 - Electrophysiological and anatomic characterisation of sites resistant to electrical isolation during circumferential pulmonary vein ablation for atrial fibrillation: A prospective study A1 - Kistler, P A1 - Rajappan, K A1 - Ho, SY A1 - Morpher, M A1 - Harris, S A1 - Abrams, D A1 - Gupta, D A1 - Sporton, S A1 - Schilling, R J1 - HEART Y1 - 2007/06// VL - 93 SN - 1355-6037 SP - A84 EP - A84 ER - TY - JFULL T1 - Measurement of troponin phosphatase activities in non-failing and failing human heart muscle A1 - Messer, A A1 - Jacques, A A1 - Marston, S J1 - J MOL CELL CARDIOL Y1 - 2007/06// VL - 42 SN - 0022-2828 SP - S153 EP - S154 ER - TY - JFULL T1 - An annual, prospective, international study of outpatients with cardiovascular disease or risk factors: design and methods of the CardioMonitor registry. A1 - Steinberg, BA A1 - Ballantyne, CM A1 - Bhatt, DL A1 - Montalescot, G A1 - Mehta, S A1 - O'Hagan, P A1 - Poole-Wilson, PA A1 - Cannon, CP J1 - Crit Pathw Cardiol Y1 - 2007/06// VL - 6 SN - 1535-2811 SP - 72 EP - 75 N2 - OBJECTIVE: To assess penetration and patterns of treatments in outpatients with cardiovascular disease (CVD) or risk factors. STUDY: An international, observational survey of physicians treating outpatients with CVD or risk factors. DESIGN AND SETTING: A unique, diversified group of physicians caring for patients with CVD or risk factors is sampled annually in countries around the world. Participating physicians register up to 15 patients with CVD or risk factors, recording demographics, medical history, clinical data, diagnoses, and medications. The registry has run annually, with different cohorts of physicians and patients each year. RESULTS: Over 9 years, the CardioMonitor registry has included participation by 18,145 physicians, registering 264,570 patients from 16 countries. Of these, 100,495 (38%) patients had cardiac disease, 26,720 (10%) had cerebrovascular disease, and 21,231 (8%) had peripheral arterial disease (not exclusive diagnoses). The remainder, 139,234 (52.6%) patients did not have clinically significant vascular disease, but had risk factors, including hypertension, diabetes, or dyslipidemia. CONCLUSION: This registry of outpatients with cardiovascular risk factors or disease with detailed medication use recorded offers new insights into trends in current practice of medicine for this large group of patients. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17667869&query_hl=1 ER - TY - JFULL T1 - The safety of amiodarone in patients with heart failure. A1 - Torp-Pedersen, C A1 - Metra, M A1 - Spark, P A1 - Lukas, MA A1 - Moullet, C A1 - Scherhag, A A1 - Komajda, M A1 - Cleland, JG A1 - Remme, W A1 - Di Lenarda, A A1 - Swedberg, K A1 - Poole-Wilson, PA A1 - COMET Investigators J1 - J Card Fail Y1 - 2007/06// VL - 13 SN - 1532-8414 SP - 340 EP - 345 N2 - BACKGROUND: Uncertainty persists about the safety and efficacy of amiodarone for the management of heart failure. METHODS AND RESULTS: We randomized 3029 patients with chronic heart failure to receive carvedilol or metoprolol and followed patients for a median of 58 months. One hundred fifty-five of 1466 patients in New York Heart Association (NYHA) Class II and 209 of 1563 in Class III or IV received amiodarone at baseline. Persistence with amiodarone treatment was high and 66% received amiodarone after 4 years. During follow-up, 38.7% and 58.9% of patients receiving amiodarone in NYHA Classes II and III + IV died versus 26.2% and 43.3% not receiving amiodarone (P < .001). This difference was maintained in multivariable analysis (hazard ratio [HR] 1.5, 95% confidence interval [CI] 1.2-1.7, P < .001). The difference was explained by an increased risk of death due to circulatory failure (HR 2.4, CI 1.9-3.1, P < .001) in patients receiving amiodarone. Sudden death was not different (HR 1.07, CI 0.8-1.4, P = .7). The increased risk was similar across NYHA classes with HR of 1.60 (CI 1.2-2.1, P < .001) in NYHA Class II versus 1.58 (CI 1.3-1.9, P < .001) in Classes III + IV. CONCLUSIONS: Treatment with amiodarone was associated with an increased risk of death from circulatory failure independent of functional class. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17602979&query_hl=1 ER - TY - JFULL T1 - Normalized left ventricular volumes and function in thalassemia major patients with normal myocardial iron. A1 - Westwood, MA A1 - Anderson, LJ A1 - Maceira, AM A1 - Shah, FT A1 - Prescott, E A1 - Porter, JB A1 - Wonke, B A1 - Walker, JM A1 - Pennell, DJ J1 - J Magn Reson Imaging Y1 - 2007/06// VL - 25 SN - 1053-1807 SP - 1147 EP - 1151 N2 - PURPOSE: To determine the reference range in thalassemia major (TM) for left ventricular (LV) function. MATERIALS AND METHODS: We used cardiovascular magnetic resonance (CMR) to measure heart volumes and function in 81 TM patients with normal myocardial T2* measurements (T2* > 20 msec) and by inference without excess myocardial iron. Forty age- and gender-matched healthy controls were also studied. RESULTS: Resting LV volumes and function normalized to body surface area differed significantly between TM patients and controls. The lower limit and the mean for ejection fraction (EF) were higher in TM patients (males 59 vs. 55%, mean 71% vs. 65%; females 63 vs. 59%, mean 71% vs. 67%; both P < 0.001). The upper limit and mean for end-diastolic volume index were higher in TM patients (males 152 vs. 105 mL/m(2), mean 97 vs. 84 mL/m(2); females 121 vs. 99 mL/m(2), mean 87 vs. 79 mL/m(2); both P < 0.05). In TM patients the cardiac index (P < 0.001) was increased. CONCLUSION: At rest, TM patients with a normal myocardial T2* have different "normal" values for LV volume and function parameters compared to controls, and this has the potential to lead to a misdiagnosis of cardiomyopathy. We present new reference "normal" ranges in TM to alleviate this problem. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17520718&query_hl=1 ER - TY - JFULL T1 - Foxs and Ets in the transcriptional regulation of endothelial cell differentiation and angiogenesis. A1 - Dejana, E A1 - Taddei, A A1 - Randi, AM J1 - Biochimica et Biophysica Acta (BBA) - Reviews on Cancer Y1 - 2007/06// IS - Issue 2 VL - Volume 1775 PB - Elsevier B.V. SP - 298 EP - 312 ER - TY - JFULL T1 - Sublingual immunotherapy for allergic rhinitis: An updated Cochrane systematic review and meta-analysis A1 - Radulovic, S A1 - Calderon, M A1 - Wilson, S A1 - Durham, S J1 - ALLERGY Y1 - 2007/06// VL - 62 SN - 0105-4538 SP - 263 EP - 263 ER - TY - JFULL T1 - Millennium development goals: an unbalanced approach to global health. A1 - Poole-Wilson, PA J1 - Nat Clin Pract Cardiovasc Med Y1 - 2007/06// VL - 4 SN - 1743-4300 SP - 289 EP - 289 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17522717&query_hl=1 ER - TY - JFULL T1 - Quality, size, and composition of pediatric endobronchial biopsies in cystic fibrosis. A1 - Regamey, N A1 - Hilliard, TN A1 - Saglani, S A1 - Zhu, J A1 - Scallan, M A1 - Balfour-Lynn, IM A1 - Rosenthal, M A1 - Jeffery, PK A1 - Alton, EW A1 - Bush, A A1 - Davies, JC J1 - Chest Y1 - 2007/06// VL - 131 SN - 0012-3692 SP - 1710 EP - 1717 N2 - BACKGROUND: Studies on airway remodeling in children with cystic fibrosis (CF) may be hampered by difficulty in obtaining evaluable endobronchial biopsy specimens because of large amounts of mucus and inflammation in the CF airway. We prospectively assessed how the quality of biopsy specimens obtained from children with CF compare with those from children with other airway diseases. METHODS: Fiberoptic bronchoscopy with endobronchial biopsy was performed in 67 CF children (age range, 0.2 to 16.8 years), 34 children with wheeze/asthma (W/A), and 64 control children with chronic respiratory symptoms. Up to three biopsy specimens were taken and stained with hematoxylin and eosin. Biopsy specimen size and structural composition were quantified using stereology. RESULTS: At least one evaluable biopsy specimen was obtained in 72% of CF children, in 79% of children with W/A, and in 72% of control subjects (difference was not significant). The use of large biopsy forceps (2.0 mm) rather than small biopsy forceps (1.0 mm) [odds ratio (OR), 5.8; 95% confidence interval (CI), 1.1 to 29.8; p = 0.037] and the number of biopsy specimens taken (odds ratio, 2.6; 95% confidence interval, 1.3 to 5.2; p = 0.006) significantly contributed to the success rate. Biopsy size and composition were similar between groups, except that CF children and those patients with W/A had a higher percentage of the biopsy specimen composed of muscle than did control subjects (median 6.2% and 9.7% vs 0.9%, respectively; p = 0.002). CONCLUSIONS: Biopsy size and quality are adequate for the study of airway remodeling in CF children as young as 2 months of age. Researchers should use large forceps when possible and take at least two biopsy specimens per patient. An increased airway smooth muscle content of the airway mucosa may contribute to the pathophysiology of CF lung disease. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17317731&query_hl=1 ER - TY - JFULL T1 - Age-dependent impairment of endothelial progenitor cells is corrected by growth hormone-mediated increase of insulin-like growth factor-1 A1 - Thum, T A1 - Hoeber, S A1 - Klink, I A1 - Stichtenoth, DO A1 - Tsilkas, D A1 - Anker, SD A1 - Poole-Wilson, PA A1 - Borlak, J A1 - Erti, G A1 - Bauersachs, J J1 - ARTERIOSCL THROM VAS Y1 - 2007/06// VL - 27 SN - 1079-5642 SP - E137 EP - E137 ER - TY - JFULL T1 - Mutations in tropomyosin that cause DCM, affect cooperativity of cardiac muscle thin filaments A1 - Marston, S A1 - Mirza, M A1 - Robinson, P A1 - Kremneva, E A1 - Levitsky, D A1 - Redwood, C A1 - EL-Mezgueldi, M J1 - J MOL CELL CARDIOL Y1 - 2007/06// VL - 42 SN - 0022-2828 SP - S166 EP - S166 ER - TY - JFULL T1 - MYBP-C mutation, expression and phosphorylation in non-failing, failing and HOCM human heart muscle A1 - Marston, S A1 - Copeland, O A1 - Jacques, A J1 - J MOL CELL CARDIOL Y1 - 2007/06// VL - 42 SN - 0022-2828 SP - S73 EP - S73 ER - TY - JFULL T1 - Can symptoms or skin prick wheal size predict the outcome of food challenge with apple? A1 - Skypala, I A1 - Calderon, M A1 - Leeds, A A1 - Durham, S J1 - ALLERGY Y1 - 2007/06// VL - 62 SN - 0105-4538 SP - 147 EP - 147 ER - TY - JFULL T1 - Exacerbations of chronic obstructive pulmonary disease. A1 - Celli, BR A1 - Barnes, PJ J1 - Eur Respir J Y1 - 2007/06// VL - 29 SN - 0903-1936 SP - 1224 EP - 1238 N2 - Exacerbations of chronic obstructive pulmonary disease are of major importance in terms of their prolonged detrimental effects on patients, the acceleration in disease progression and high healthcare costs. There is still debate about how exacerbations should be defined and graded, and their mechanisms are poorly understood. The major causal agents are either bacteria or viral infections, or a combination of the two. Noninfective causes include air pollution and pulmonary embolus but, in some patients, no cause is identified. Exacerbations represent an increase in the inflammation that is present in the stable state, with increased numbers of inflammatory cells (particularly neutrophils), cytokines, chemokines and proteases in the airways, and increased concentrations of certain cytokines and C-reactive protein in the blood. There are presently no reliable biomarkers with which to predict exacerbations. Exacerbations have a long-lasting adverse influence on health status. High doses of bronchodilators are the mainstay of treatment and systemic corticosteroids have some benefit. The routine use of antibiotics remains controversial but they are of benefit with exacerbations of a bacterial origin. Noninvasive ventilation is beneficial in preventing the need for intubation and its important complications but it is not certain whether its use in stable patients prevents exacerbations. Although important advances have been made, more effective treatments are needed in the future for prevention and treatment of exacerbations. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17540785&query_hl=1 ER - TY - JFULL T1 - Basolateral P2X4-like receptors regulate the extracellular ATP-stimulated epithelial Na+ channel activity in renal epithelia. A1 - Zhang, Y A1 - Sanchez, D A1 - Gorelik, J A1 - Klenerman, D A1 - Lab, M A1 - Edwards, C A1 - Korchev, Y J1 - Am J Physiol Renal Physiol Y1 - 2007/06// VL - 292 SN - 0363-6127 SP - F1734 EP - F1740 N2 - Extracellular ATP initiates potent effects on sodium transport across renal epithelia through membrane-associated purinergic receptors. Dependent on the location of these receptors, ATP either inhibits or stimulates sodium reabsorption. Using A6 cells, transepithelial electrical resistance measurements, and scanning ion conductance microscopy, we have identified the purinergic receptors involved in the stimulatory action on the epithelial cell basolateral plasma membrane. Addition of the potent P2X(4) receptor agonist 2-methylthio-ATP (2MeSATP) to the basolateral side of the A6 monolayer stimulated amiloride-sensitive sodium conductance and produced similar cell morphological changes to those found with ATPgammaS, aldosterone, or hypotonic stress. The agonist potency order determined by sodium conductance changes of the monolayer was: 2MeSATP >or= ATPgammaS > CTP, a similar agonist potency profile to that of cloned P2X(4) receptors but with higher sensitivity for beta, gamma-methylene-ATP and alpha,beta-methylene-ATP. We further demonstrated that the ATP effect on sodium transport was potentiated by ivermectin, not blocked by suramin and PPADS, enhanced by Zn(2+) but not by Cu(2+), and significantly reduced but not totally inhibited by brilliant blue G. These results led us to conclude that basolateral P2X(4)-like receptors were involved. We suggest that there is a reciprocal purinergic system acting both at a basolateral and apical location for control of Na(+) transport. This requires a mechanism within the cell that leads to either basolateral or apical ATP release to regulate renal tubular function. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17356127&query_hl=1 ER - TY - JFULL T1 - Grass tablet immunotherapy consistently relieves seasonal eye and nasal symptoms (including blocked nose) in consecutive seasons A1 - Rak, S A1 - de Monchy, J A1 - Emminger, W A1 - Durham, S A1 - Kapp, A A1 - Colombo, G A1 - Riis, B A1 - Dahl, R J1 - ALLERGY Y1 - 2007/06// VL - 62 SN - 0105-4538 SP - 237 EP - 237 ER - TY - JFULL T1 - Relative contribution of electrical and nonelectrical (structural) remodelling on the atrial fibrillation circuit size in the chronic goat model of atrial fibrillation A1 - Kirubakaran, S A1 - Hall, M A1 - Peters, N A1 - Garratt, C J1 - HEART Y1 - 2007/06// VL - 93 SN - 1355-6037 SP - A56 EP - A56 ER - TY - JFULL T1 - Medium-term echocardiographic assessment of heart failure patients implanted with an axial flow LVAD A1 - Jin, X A1 - Westaby, S A1 - Pepper, J A1 - Poole-Wilson, P A1 - Banning, A J1 - HEART Y1 - 2007/06// VL - 93 SN - 1355-6037 SP - A40 EP - A40 ER - TY - JFULL T1 - Pollen-food syndrome in United Kingdom subjects - which aeroallergens are commonly involved? A1 - Skypala, I A1 - Calderon, M A1 - Leeds, A A1 - Durham, S J1 - ALLERGY Y1 - 2007/06// VL - 62 SN - 0105-4538 SP - 358 EP - 358 ER - TY - JFULL T1 - Repeated allergen inhalation induces cytoskeletal remodeling in smooth muscle from rat bronchioles. A1 - McVicker, CG A1 - Leung, SY A1 - Kanabar, V A1 - Moir, LM A1 - Mahn, K A1 - Chung, KF A1 - Hirst, SJ J1 - Am J Respir Cell Mol Biol Y1 - 2007/06// VL - 36 SN - 1044-1549 SP - 721 EP - 727 N2 - Airway hyperresponsiveness (AHR) is associated with airway wall structural remodeling and alterations in airway smooth muscle (ASM) function. Previously, in bronchioles from Brown Norway rats challenged by repeated ovalbumin (OVA) inhalation, we have reported increased force generation and depletion of smooth muscle contractile proteins. Here, we investigated if cytoskeletal changes in smooth muscle could account for this paradox. Sensitized rats (n = 5/group) were repeatedly challenged with OVA or saline, and the lungs were removed 24 h after the last challenge. Levels of globular (G) and filamentous (F) actin in bronchioles were determined by DNase I inhibition and contraction assessed in intact small bronchioles using a myograph. DNase I inhibition assays showed that G-actin monomers were more abundant ( approximately 1F:2G) in extracts from resting small bronchioles from OVA- or saline-challenged animals. However, while contractile protein levels in bronchioles were reduced by OVA (P < 0.05), the proportion of F:G actin was 1.8-fold greater compared with saline challenge (P < 0.05). Consistent with induction of F-actin after OVA challenge, increases in maximum tension development to carbachol or KCl in small bronchioles from OVA-challenged animals were abrogated (P < 0.01) by actin cytoskeleton disruption with 0.5 microM latrunculin A. Cytoskeletal stabilization of F-actin with 0.1 microM jasplakinolide potentiated maximum contractions to carbachol or KCl (P < 0.05) in bronchioles from OVA- but not saline-treated rats. We conclude that alterations in the composition and/or arrangement of the contractile apparatus after OVA exposure confer enhanced contractile responses, possibly as a result of increased F-actin content. Such a mechanism may have relevance for AHR found in allergic asthma. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17272821&query_hl=1 ER - TY - JFULL T1 - Follistatin gene expression is elevated in heart failure and decreases following recovery A1 - Lara-Pezzi, E A1 - Felkin, LE A1 - Birks, E A1 - Yacoub, MH A1 - Rosenthal, N A1 - Barton, PJ J1 - J MOL CELL CARDIOL Y1 - 2007/06// VL - 42 SN - 0022-2828 SP - S147 EP - S147 ER - TY - JFULL T1 - A T2/T2 magnetic resonance imaging (MRI) study of iron overload in hemopoietic stem cell transplant recipients A1 - Au, WY A1 - Lam, W A1 - Chu, W A1 - Tam, S A1 - Wong, WK A1 - Pennell, DJ A1 - Lie, AK A1 - Liang, R J1 - AM J HEMATOL Y1 - 2007/06// VL - 82 SN - 0361-8609 SP - 598 EP - 598 ER - TY - JFULL T1 - The use of contrast echocardiography for the detection of cardiac shunts A1 - Soliman, OII A1 - Geleijnse, ML A1 - Meijboom, FJ A1 - Nemes, A A1 - Kamp, O A1 - Nihoyannopoulos, P A1 - Masani, N A1 - Feinstein, SB A1 - Ten Cate, FJ J1 - EUR J ECHOCARDIOGR Y1 - 2007/06// VL - 8 SP - S2 EP - S12 N2 - Recently, debate has erupted about the clinical significance of cardiovascular shunts. Several major health problems such as stroke and migraine have been associated with patent foramen ovate (PFO) with right-to-left shunt (RLS). The nature of the relationship between these syndromes and PFO is not clearly understood. Technical advances have led to more therapeutic options including device closure of PFO, hence prevention of such a PFO-related stroke has become feasible. Therefore, optimal diagnosis of PFO has become of greater clinical importance. Contrast echocardiography with non-transpulmonary contrast agents has been the cornerstone in diagnosis of PFO with RLS for over four decades. Despite being a relatively invasive procedure, transesophageal echocardiography (TEE) is considered the gold standard for detection of RLS. Several other echocardiographic techniques such as transthoracic echocardiography (TTE) with second harmonic imaging and transcranial Doppler ultrasonography (TCD) have shown increased sensitivity and specificity compared to TEE for the detection of PFO with RLS. Moreover, improvement of skills and techniques used for detection of these shunts has led to greater detection of small and large sized RLS in the echocardiographic laboratory. This review gives and overview of the echocardiographic techniques, contrast agents and manoeuvres used for detection of the major cardiovascular shunts and their clinical relevance to major health problems. (c) 2007 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved. ER - TY - JFULL T1 - Restoring force is lower in human donor and hcm myocytes compared with rat A1 - Hoskins, AC A1 - Jacques, AM A1 - Marston, SB A1 - Kentish, JC J1 - J MOL CELL CARDIOL Y1 - 2007/06// VL - 42 SN - 0022-2828 SP - S119 EP - S120 ER - TY - JFULL T1 - Incident atrial fibrillation and new heart failure: The chicken or the egg? Insights from the imperial college new AF study A1 - Martins, J A1 - Fox, K A1 - Wood, D A1 - Lefroy, D A1 - Collier, T A1 - Peters, N J1 - HEART Y1 - 2007/06// VL - 93 SN - 1355-6037 SP - A30 EP - A30 ER - TY - JFULL T1 - Altered function and post-translational modification of contractile proteins in myectomy samples from HOCM patients A1 - Gallon, C A1 - Jacques, A A1 - Messer, A A1 - Tsang, V A1 - McKenna, W A1 - Marston, S J1 - J MOL CELL CARDIOL Y1 - 2007/06// VL - 42 SN - 0022-2828 SP - S167 EP - S167 ER - TY - JFULL T1 - Progressive effect of grass tablet immunotherapy during long-term treatment in patients with rhinoconjunctivitis A1 - Emminger, W A1 - Dahl, R A1 - Kappp, A A1 - Colombo, G A1 - de Monchy, J A1 - Rak, S A1 - Riis, B A1 - Durham, S J1 - ALLERGY Y1 - 2007/06// VL - 62 SN - 0105-4538 SP - 240 EP - 240 ER - TY - JFULL T1 - Asthma: 1987-2007. What have we achieved and what are the persisting challenges? A1 - Partridge, MR J1 - Prim Care Respir J Y1 - 2007/06// VL - 16 SN - 1471-4418 SP - 145 EP - 148 N2 - Despite an increasing prevalence of asthma, enormous advances have been made in our understanding and management of asthma over the last 20 years. Work begun two or three decades ago demonstrated the inflammatory nature of asthma, emphasised the need for regular treatment, and introduced the goal of maintaining normal lung function. More recent work demonstrated the benefits of adding a long-acting inhaled beta-agonist to low-dose inhaled steroids as an alternative to escalating the steroid dosage. More recently still, studies and regulatory approval have led to the possibility of the same inhaler being used for maintenance therapy and for relief. However, these new ways of using old medicines, along with some new medicines such as omalizumab, should not detract us from looking beyond the prescription. The challenges facing us now are to determine why the prevalence of asthma has increased so dramatically, and in the absence of a cure how we can best help increasing numbers of people with asthma benefit from the treatment which is available. This will involve a much more aggressive implementation of advice regarding self-management education and a restructuring of health services to provide a service that is cognisant of the fact that, like us, patients are increasingly busy - and if they are to benefit from regular review, that review needs to be offered at a convenient time and by convenient methods. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17530142&query_hl=1 ER - TY - JFULL T1 - Atopy, wheeze and bronchial responsiveness in young Chilean adults. Do dietary antioxidants matter? A1 - García-Larsen, V A1 - Chinn, S A1 - Arts, IC A1 - Amigo, H A1 - Rona, RJ J1 - Allergy Y1 - 2007/06// VL - 62 SN - 0105-4538 SP - 714 EP - 715 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17508981&query_hl=1 ER - TY - JFULL T1 - Impact of tobacco-smoke on key signaling pathways in the innate immune response in lung macrophages. A1 - Birrell, MA A1 - Wong, S A1 - Catley, MC A1 - Belvisi, MG J1 - J Cell Physiol Y1 - 2007/05/31/ SN - 0021-9541 N2 - Many of the healthcare consequences of cigarette smoking could be due to its ability to compromise the immune system, and in respiratory diseases like chronic obstructive pulmonary disease (COPD), a constant low level of infection could be responsible for some of the symptoms/pathology. The aim was to assess the impact of cigarette smoke (CS) on the release of innate effector cytokines in THP-1 cells and human lung macrophages, and to determine the molecular mechanism behind the altered response. Cells were exposed to CS with and without endotoxin stimulus, cytokines, glutathione, mitogen-activated protein kinase (MAPK) phosphorylation, IkappaB kinase-2 (IKK-2) activity, nuclear factor kappa B (NF-kappaB), and activator protein-1 (AP-1) pathway activation was measured. Attempts were made to mimic or block the effect of CS by using nicotine, nitric oxide donors/inhibitors, prostanoid inhibitors, and anti-oxidants. Results showed that CS initially delayed the production of "innate" cytokines (e.g., IL-1beta and IL-6) and reduced glutathione levels. This was associated with a reduction in NF-kappaB pathway activation, which suggested a causative link. CS also increased the phosphorylation of MAPK's and the production of IL-8 but interestingly only in stimulated cells. Exogenous glutathione treatment reversed both these effects of CS, which suggests that this molecule may play a central role. In conclusion, this data provides a novel mechanistic explanation for why smokers have increased prevalence/severity of respiratory infections. In addition, the suppression of the innate response is accompanied by an increase in the neutrophil chemoattractant, IL-8, which may suggest a link to the pathogenesis of smoking-related inflammatory disease. J. Cell. Physiol. (c) 2007 Wiley-Liss, Inc. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17541958&query_hl=1 ER - TY - JFULL T1 - Response to letter regarding article, "anabolic deficiency in men with chronic heart failure: Prevalence and detrimental impact on survival" A1 - Jankowska, EA A1 - Biel, B A1 - Majda, J A1 - Banasiak, W A1 - Ponikowski, P A1 - Lopuszanska, M A1 - Szklarska, A A1 - Anker, SD A1 - Poole-Wilson, PA A1 - Medras, M J1 - CIRCULATION Y1 - 2007/05/29/ VL - 115 SN - 0009-7322 SP - E549 EP - E549 ER - TY - JFULL T1 - Corticosteroids and beta2 agonists differentially regulate rhinovirus-induced interleukin-6 via distinct Cis-acting elements. A1 - Edwards, MR A1 - Haas, J A1 - Panettieri, RA A1 - Johnson, M A1 - Johnston, SL J1 - J Biol Chem Y1 - 2007/05/25/ VL - 282 SN - 0021-9258 SP - 15366 EP - 15375 N2 - Interleukin-6 (IL-6) is a proinflammatory cytokine up-regulated by rhinovirus infection during acute exacerbations of asthma and chronic obstructive pulmonary disease. The role of IL-6 during exacerbations is unclear; however, it is believed IL-6 could contribute to airway and systemic inflammation. In this study we investigate the effects of common asthma treatments fluticasone propionate and beta(2) agonists salmeterol and salbutamol on IL-6 production in BEAS-2B and primary bronchial epithelial cells. Salmeterol and salbutamol enhanced rhinovirus- and IL-1beta-induced IL-6 production; however, fluticasone treatment caused a reduction of IL-6 protein and mRNA. Combined activity of salmeterol and fluticasone at equimolar concentrations had no effect on rhinovirus or IL-1beta induction of IL-6. The induction of IL-6 by salmeterol was dependent upon the beta(2) receptor and could also be induced by cAMP or cAMP-elevating agents forskolin and rolipram. Using transfection of IL-6 promoter reporter constructs, dominant negative mutants, and electromobility shift assays, it was found that NF-kappaB was the only transcription factor required for rhinovirus induction of IL-6 gene expression. Salmeterol caused an augmentation of rhinovirus-induced promoter activation via a mechanism dependent upon the c/EBP and/or CRE (cyclic AMP response element) cis-acting sites. The suppressive effect of FP was dependent upon distinct glucocorticoid response element sequences proximal to the transcriptional start site within the IL-6 promoter. The data demonstrate that beta(2) agonists can augment IL-6 expression by other stimuli in an additive manner via cyclic AMP and that the negative effect of steroids is mediated by glucocorticoid response elements within the IL-6 promoter. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17395587&query_hl=1 ER - TY - JFULL T1 - Airway remodelling in children with cystic fibrosis. A1 - Hilliard, TN A1 - Regamey, N A1 - Shute, J A1 - Nicholson, A A1 - Alton, EW A1 - Bush, A A1 - Davies, JC J1 - Thorax Y1 - 2007/05/25/ SN - 0040-6376 N2 - BACKGROUND: The relationship between airway structural changes and inflammation is unclear in early cystic fibrosis (CF) lung disease. OBJECTIVE: To determine changes of airway remodelling in children with CF, compared with appropriate disease and healthy controls. METHODS: Bronchoalveolar lavage and endobronchial biopsy were performed in a cross-sectional study of 43 children with CF (aged 0.3 to 16.8 years), 7 children with primary ciliary dyskinesia (PCD), 26 children with chronic respiratory symptoms (CRS) investigated for recurrent infection and/or cough, and 7 control children with no lower airway symptoms. Inflammatory cells, cytokines, proteases and matrix constituents were measured in bronchoalveolar lavage fluid (BALF). Reticular basement membrane (RBM) thickness was measured on biopsies using light microscopy. RESULTS: Increased concentrations of elastin, glycosaminoglycans and collagen were found in CF BALF compared to the CRS group and controls, and each correlated with elastase activity, MMP-9 and neutrophil concentration. Levels of inflammatory markers and matrix components were similar in the PCD and CF groups. In the CF group, both elastin concentration and MMP-9:TIMP-1 ratio, correlated negatively with FEV1 (r=-0.45, p<0.05 and r=-0.47, p<0.05 respectively). Median RBM thickness was greater in the CF group (5.9 mm) than controls (4.0 mm, p<0.01), and correlated with transforming growth factor-beta1 (TGF-beta1) concentration (r=0.53, p=0.01); however, there was no correlation with pulmonary function. CONCLUSIONS: This study provides evidence for two forms of airway remodelling in children with CF: firstly, matrix breakdown which correlates with proteases and pulmonary function, and secondly RBM thickening, related to TGF-beta1 concentration. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17526676&query_hl=1 ER - TY - JFULL T1 - Prevention of death in COPD. A1 - Barnes, PJ J1 - N Engl J Med Y1 - 2007/05/24/ VL - 356 SN - 1533-4406 SP - 2211; author reply 2213 EP - 2214; author reply 2213 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17522406&query_hl=1 ER - TY - JFULL T1 - Antiphase oscillations of endothelium and smooth muscle [Ca(2+)](i) in vasomotion of rat mesenteric small arteries. A1 - Rahman, A A1 - Hughes, A A1 - Matchkov, V A1 - Nilsson, H A1 - Aalkjær, C J1 - Cell Calcium Y1 - 2007/05/22/ SN - 0143-4160 N2 - The mechanisms leading to vasomotion in the presence of noradrenaline and inhibitors of the sarcoplasmic/endoplasmic reticulum calcium ATPase were investigated in isolated rat mesenteric small arteries. Isobaric diameter and isometric force were measured together with membrane potential in endothelial cells and smooth muscle cells (SMC). Calcium in the endothelial cells and SMC was imaged with confocal microscopy. In the presence of noradrenaline and cyclopiazonic acid, ryanodine-insensitive oscillations in tone were produced. The frequency was about 1min(-1) and amplitude about 70% of the maximal tone. The amplitude was reduced by indomethacin and increased with L-NAME. Vasomotion was inhibited by nifedipine and by 40mM potassium. The frequency was increased and amplitude decreased by removal of the endothelium and by application of charybdotoxin and apamin. The vasomotion was associated with in-phase oscillations of membrane potential in endothelial cells and SMC and oscillations of [Ca(2+)](i) that were in near anti-phase. We suggest a working model for the generation of oscillation based on a membrane oscillator where ion channels in both endothelial cells and SMC interact via a current running between the two cell types through myoendothelial gap junctions, which sets up a near anti-phase oscillation of [Ca(2+)](i) in the two cell types. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17524481&query_hl=1 ER - TY - JFULL T1 - HRT and the primary prevention of cardiovascular disease. A1 - Stevenson, JC J1 - Maturitas Y1 - 2007/05/20/ VL - 57 SN - 0378-5122 SP - 31 EP - 34 N2 - Observational studies have consistently shown a benefit of hormone replacement therapy (HRT) on coronary heart disease (CHD), but some randomised studies have not shown any significant effect. Thus questions still remains as to whether HRT is beneficial for CHD, and in whom this benefit might be achieved. The biological effects of oestrogen on the cardiovascular system have been extensively studied, and beneficial effects on metabolic CHD risk factors, as well as on arterial function and on surrogate clinical markers of CHD, have been demonstrated. Thus it seems implausible that HRT should not benefit CHD in postmenopausal women. Most randomised trials using clinical outcomes have studied just one dose of one HRT regimen, a dose inappropriately high with the average starting age of the participants being in their mid-60s. The observational population studies largely comprise women starting on HRT at appropriate dose around the age of menopause, i.e. early 50s. In fact, it was the older women in the randomised trials that failed to show benefit, whereas there was a trend to benefit in the younger ones for whom the starting dose of HRT was appropriate. Furthermore, a pilot study of lower dose HRT in older women did not show any cardiovascular harm. Inappropriately high doses of oestrogen could cause cardiovascular harm due to transient disturbances in thrombogenesis and vascular remodelling. Whilst the greatest CHD benefit may be seen by starting HRT in the early postmenopause, this does not exclude benefit in older women given appropriate low dose therapy. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17383835&query_hl=1 ER - TY - JFULL T1 - Occluding the left atrial appendage: anatomical considerations. A1 - Su, P A1 - McCarthy, KP A1 - Ho, SY J1 - Heart Y1 - 2007/05/08/ SN - 1468-201X N2 - OBJECTIVE: Occlusion of the left atrial appendage (LAA) is proposed to reduce the risk of thromboembolic events in patients with atrial fibrillation. We examined the LAA and its relationship to neighbouring structures that may be put at risk when intervening to occlude its os. METHODS: Thirty-one heart specimens were examined grossly. Four of the LAA were processed for histological examination and endocasts were made from 11 appendages. The diameters of the LAA os and proximity to the left superior pulmonary vein, mitral valve and left anterior descending artery were measured and areas of thin atrial wall in the vicinity were noted. RESULTS: The LAA orifice was oval-shaped in all cases with a mean diameter of 17.4+/-4 mm (range= 10-24.1 mm). The mean distances of the LAA orifice to the left superior pulmonary vein and mitral valve were 11.1+/-4.1 mm and 10.7+/-2.4 mm respectively. The left anterior descending, circumflex artery and, in 6 cases, the sinus node artery were in close proximity to the LAA. Pits or troughs and areas of thin atrial wall were found in 57.7% of hearts within a 20.9 mm radius from the os. Histology showed small crevices and areas of very thin wall within the trabeculated appendage. CONCLUSIONS: The LAA orifice is oval shaped and thin areas of appendage wall and atrial wall are common. Potentially, the left superior pulmonary vein, mitral valve, and anterior descending coronary artery can be at risk during occlusion of the os. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17488765&query_hl=1 ER - TY - JFULL T1 - Influence of socioeconomic status on survival after primary aortic or mitral valve replacement. A1 - Bagger, JP A1 - Edwards, MB A1 - Taylor, KM J1 - Heart Y1 - 2007/05/04/ SN - 1468-201X N2 - Objectives We sought to evaluate whether socioeconomic status influences outcome after first-time single aortic or mitral valve replacement. Setting National Heart Valve registry. Design and Patients Between 1st January 1986 and 31st December 2001, 51,844 consecutive patients who underwent primary aortic or mitral valve replacement were registered on the United Kingdom (UK) Heart Valve Registry. Data included age, gender, valve position, type of valve implant, postcode, follow-up time, date and cause of death. The Carstairs deprivation score (1991 Census data for the UK) was used to stratify cases by level of social deprivation according to postcodes. Results Both 30-day and 1-year survival/mortality rates were similar across all socioeconomic levels. However, long-term survival rate (up to 15 years) was significantly higher in the least deprived socioeconomic level as compared to the two most deprived levels. There was a 18% lower survival rate amongst women in the most deprived levels (35.9%, 95% CI: 32.4-39.4) versus the least deprived level (43.7%, 95% CI: 38.1-49.2, P<0.004). In males, survival in the most deprived levels (39.5%, 95% CI: 36.4-42.5) was 7% lower than in the least deprived level (42.7%, 95% CI: 37.7-47.7, P< 0.005). Biological valve, mitral position, female gender, and low socioeconomic status were all associated with long-term mortality. Conclusions A disadvantaged social background influences negatively long-term survival after aortic or mitral valve replacement especially among women. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17483126&query_hl=1 ER - TY - JFULL T1 - The effect of mutations in alpha-tropomyosin (E40K and E54K) that cause familial dilated cardiomyopathy on the regulatory mechanism of cardiac muscle thin filaments. A1 - Mirza, M A1 - Robinson, P A1 - Kremneva, E A1 - Copeland, O A1 - Nikolaeva, O A1 - Watkins, H A1 - Levitsky, D A1 - Redwood, C A1 - El-Mezgueldi, M A1 - Marston, S J1 - J Biol Chem Y1 - 2007/05/04/ VL - 282 SN - 0021-9258 SP - 13487 EP - 13497 N2 - E40K and E54K mutations in alpha-tropomyosin cause inherited dilated cardiomyopathy. Previously we showed, using Ala-Ser alpha-tropomyosin (AS-alpha-Tm) expressed in Escherichia coli, that both mutations decrease Ca(2+) sensitivity. E40K also reduces V(max) of actin-Tm-activated S-1 ATPase by 18%. We investigated cooperative allosteric regulation by native Tm, AS-alpha-Tm, and the two dilated cardiomyopathy-causing mutants. AS-alpha-Tm has a lower cooperative unit size (6.5) than native alpha-tropomyosin (10.0). The E40K mutation reduced the size of the cooperative unit to 3.7, whereas E54K increased it to 8.0. For the equilibrium between On and Off states, the K(T) value was the same for all actin-Tm species; however, the K(T) value of actin-Tm-troponin at pCa 5 was 50% less for AS-alpha-Tm E40K than for AS-alpha-Tm and AS-alpha-Tm E54K. K(b), the "closed" to "blocked" equilibrium constant, was the same for all tropomyosin species. The E40K mutation reduced the affinity of tropomyosin for actin by 1.74-fold, but only when in the On state (in the presence of S-1). In contrast the E54K mutation reduced affinity by 3.5-fold only in the Off state. Differential scanning calorimetry measurements of AS-alpha-Tm showed that domain 3, assigned to the N terminus of tropomyosin, was strongly destabilized by both mutations. Additionally with AS-alpha-Tm E54K, we observed a unique new domain at 55 degrees C accounting for 25% of enthalpy indicating stabilization of part of the tropomyosin. The disease-causing mechanism of the E40K mutation may be accounted for by destabilization of the On state of the thin filaments; however, the E54K mutation has a more complex effect on tropomyosin structure and function. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17360712&query_hl=1 ER - TY - JFULL T1 - COMPARISON OF TEMPORARY BIFOCAL RIGHT VENTRICULAR PACING AND BIVENTRICULAR PACING FOR HEART FAILURE: EVALUATION BY TISSUE DOPPLER IMAGING. A1 - Lane, RE A1 - Mayet, J A1 - Peters, NS A1 - Davies, DW A1 - Chow, AW J1 - Heart Y1 - 2007/05/04/ SN - 1468-201X N2 - Introduction The complications and limitations of biventricular pacing largely relate to left ventricular (LV) pacing. We tested an alternative approach of simultaneously pacing the right ventricular (RV) apex and outflow tract (RVOT) or bifocal right venntricular pacing (BRVP) to provide cardiac resynchronization. Methods 21 consecutive patients with heart failure and severely impaired LV function were studied. Ejection fraction and tissue Doppler data were collected at baseline, during BRVP and biventricular pacing using a temporary pacing protocol. Results BRVP was achieved in all patients without complication. BRVP significantly reduced mean baseline intra LV, inter LV-RV and global mechanical dyssynchrony from 71 +/- 35 to 44 +/- 18ms, p=0.003; 86 +/- 42 to 57 +/- 33ms, p=0.029; and 157 +/- 67 to 101 +/- 42ms, p=0.005 respectively; and increased ejection fraction from 21 +/- 8 to 29 +/- 7%, p=0.002. Compared with BRVP, reductions in intra LV, inter LV-RV and global mechanical dyssynchrony were superior with biventricular pacing (31 +/- 12ms, p=0.014, 36 +/- 27ms, p=0.008 and 67 +/- 34ms, p=0.01 compared with BRVP respectively); but improvements in ejection fraction were similar (26 +/- 9%, p=NS). Conclusions In patients with heart failure, superior mechanical resynchronization is achieved with biventricular pacing compared with BRVP. BRVP may be useful when LV lead placement is not possible. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17483133&query_hl=1 ER - TY - JFULL T1 - Unexpected failure of anti-tumor necrosis factor therapy in chronic obstructive pulmonary disease A1 - Barnes, PJ J1 - AM J RESP CRIT CARE Y1 - 2007/05/01/ VL - 175 SN - 1073-449X SP - 866 EP - 867 ER - TY - JFULL T1 - Osteopontin has a crucial role in allergic airway disease through regulation of dendritic cell subsets. A1 - Xanthou, G A1 - Alissafi, T A1 - Semitekolou, M A1 - Simoes, DC A1 - Economidou, E A1 - Gaga, M A1 - Lambrecht, BN A1 - Lloyd, CM A1 - Panoutsakopoulou, V J1 - Nat Med Y1 - 2007/05// VL - 13 SN - 1078-8956 SP - 570 EP - 578 N2 - Osteopontin (Opn) is important for T helper type 1 (T(H)1) immunity and autoimmunity. However, the role of this cytokine in T(H)2-mediated allergic disease as well as its effects on primary versus secondary antigenic encounters remain unclear. Here we demonstrate that OPN is expressed in the lungs of asthmatic individuals and that Opn-s, the secreted form of Opn, exerts opposing effects on mouse T(H)2 effector responses and subsequent allergic airway disease: pro-inflammatory at primary systemic sensitization, and anti-inflammatory during secondary pulmonary antigenic challenge. These effects of Opn-s are mainly mediated by the regulation of T(H)2-suppressing plasmacytoid dendritic cells (DCs) during primary sensitization and T(H)2-promoting conventional DCs during secondary antigenic challenge. Therapeutic administration of recombinant Opn during pulmonary secondary antigenic challenge decreased established T(H)2 responses and protected mice from allergic disease. These effects on T(H)2 allergic responses suggest that Opn-s is an important therapeutic target and provide new insight into its role in immunity. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17435770&query_hl=1 ER - TY - JFULL T1 - Differential flow analysis of exhaled nitric oxide in patients with asthma of differing severity. A1 - Brindicci, C A1 - Ito, K A1 - Barnes, PJ A1 - Kharitonov, SA J1 - Chest Y1 - 2007/05// VL - 131 SN - 0012-3692 SP - 1353 EP - 1362 N2 - BACKGROUND: The majority of asthmatic patients achieve control of their illness; others do not. It is therefore crucial to validate/develop strategies that help the clinician monitor the disease, improving the response to treatment. METHODS: We have quantified the inflammation in central and peripheral airways by measuring exhaled nitric oxide (NO) at multiple exhalation flows in 56 asthmatics at different levels of severity (mild, n = 10; moderate stable, n = 17; moderate during exacerbation, n = 11; severe, n = 18, 7 of whom were receiving oral corticosteroids) and 18 healthy control subjects. The reproducibility of the measurement was also assessed. RESULTS: Bronchial NO (Jno) in patients with mild asthma (2,363 +/- 330 pL/s) [mean +/- SD] was higher than in patients with moderate stable asthma (1,300 +/- 59 pL/s, p < 0.0005), in patients with severe asthma receiving inhaled corticosteroids (ICS) [1,015 +/- 67 pL/s, p < 0.0005], and healthy control subjects (721 +/- 22 pL/s, p < 0.0001). There were no differences between Jno in patients with mild asthma compared to patients with severe asthma receiving ICS and oral corticosteroids (2,225 +/- 246 pL/s). Patients with exacerbations showed a higher Jno (3,475 +/- 368.9 pL/s, p < 0.05) compared to the other groups. Alveolar NO was higher in patients with severe asthma receiving oral corticosteroids (3.0 +/- 0.1 parts per billion [ppb], p < 0.0001) than in the other groups but was not significantly higher than in patients with moderate asthma during exacerbation (2.8 +/- 0.3 ppb). No differences were seen in NO diffusion levels between the different asthma groups. All the measurements were highly reproducible and free of day-to-day and diurnal variations. CONCLUSIONS: Differential flow analysis of exhaled NO provides additional information about the site of inflammation in asthma and may be useful in assessing the response of peripheral inflammation to therapy. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17494785&query_hl=1 ER - TY - JFULL T1 - Letter by Rose and Dunn regarding article, "Expression of heat shock protein 27 in human atherosclerotic plaques and increased plasma level of heat shock protein 27 in patients with acute coronary syndrome" A1 - Rose, ML A1 - Dunn, MJ J1 - CIRCULATION Y1 - 2007/05/01/ VL - 115 SN - 0009-7322 SP - E434 EP - E434 ER - TY - JFULL T1 - Antiendothelial cell antibodies mediate enhanced leukocyte adhesion to cytokine-activated endothelial cells through a novel mechanism requiring cooperation between Fc{gamma}RIIa and CXCR1/2. A1 - Florey, OJ A1 - Johns, M A1 - Esho, OO A1 - Mason, JC A1 - Haskard, DO J1 - Blood Y1 - 2007/05/01/ VL - 109 SN - 0006-4971 SP - 3881 EP - 3889 N2 - Antiendothelial cell antibodies (AECAs) are commonly detectable in diseases associated with vascular injury, including systemic lupus erythematosus (SLE), systemic sclerosis, Takayasu arteritis, Wegener granulomatosis, Behçet syndrome, and transplant arteriosclerosis. Here, we explore the hypothesis that these antibodies might augment polymorphonuclear leukocyte (PMN) adhesion to endothelium in inflammation. Initially, we established that a mouse IgG mAb bound to endothelial cells (ECs) significantly increased PMN adhesion to cytokine-stimulated endothelium in an FcgammaRIIa-dependent manner. Neutralizing antibodies, and adenoviral transduction of resting ECs, demonstrated that the combination of E-selectin, CXCR1/2, and beta(2) integrins is both necessary and sufficient for this process. We observed an identical mechanism using AECA IgG isolated directly from patients with SLE. Assembled immune complexes also enhanced PMN adhesion to endothelium, but, in contrast to adhesion because of AECAs, this process did not require CXCR1/2, was not inhibited by pertussis toxin, and was FcgammaRIIIb rather than FcgammaRIIa dependent. These data are the first to demonstrate separate nonredundant FcgammaRIIa and FcgammaRIIIb-mediated mechanisms by which EC-bound monomeric IgG and assembled immune complexes amplify leukocyte adhesion under dynamic conditions. Furthermore, the observation that FcgammaRIIa and CXCR1/2 cooperate to enhance PMN recruitment in the presence of AECAs suggests a mechanism whereby AECAs may augment tissue injury during inflammatory responses. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17244681&query_hl=1 ER - TY - JFULL T1 - The burden of diabetes and its complications: trends and implications for intervention. A1 - Chaturvedi, N J1 - Diabetes Res Clin Pract Y1 - 2007/05// VL - 76 Suppl 1 SN - 0168-8227 SP - S3 EP - S12 N2 - Much of the burden of diabetes is due to the development of vascular complications, including cardiovascular diseases, retinopathy and nephropathy. Improvements in patient management to promote tight control of glycaemia have helped to reduce the prevalence of microvascular complications, but cardiovascular diseases continue to be the leading cause of death in patients with type 2 diabetes. Globally, the number of people with diabetes is predicted to almost double over the next 30 years, with much of this increase occurring in developing countries. The growing prevalence of obesity is the major factor driving the increasing prevalence of type 2 diabetes, and the increase in obesity in adolescents is of particular concern. Consequently, the overall number of people with the vascular complications of diabetes is also predicted to increase. Prevention of diabetes is the best strategy for reducing the risk of complications, and screening of high-risk individuals is already being promoted in some countries. Lifestyle changes, focusing on diet, exercise and weight loss are effective in preventing diabetes in such people. However, more information is required about the long-term sustainability of these changes, and programmes also need to be adapted to meet the needs of developing countries. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17343954&query_hl=1 ER - TY - JFULL T1 - 'End-stage' hypertrophic cardiomyopathy: from mystery to model. A1 - Yacoub, MH A1 - Olivotto, I A1 - Cecchi, F J1 - Nat Clin Pract Cardiovasc Med Y1 - 2007/05// VL - 4 SN - 1743-4300 SP - 232 EP - 233 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17457348&query_hl=1 ER - TY - JFULL T1 - The effects of adaptive servo ventilation on cerebral vascular reactivity in patients with congestive heart failure and sleep-disordered breathing. A1 - Morrell, MJ A1 - Meadows, GE A1 - Hastings, P A1 - Vazir, A A1 - Kostikas, K A1 - Simonds, AK A1 - Corfield, DR J1 - Sleep Y1 - 2007/05/01/ VL - 30 SN - 0161-8105 SP - 648 EP - 653 N2 - STUDY OBJECTIVE: Hypercapnic cerebral vascular reactivity (HCVR) is reduced in patients with congestive heart failure (CHF) and sleep-disordered breathing (SDB); this may be associated with an increased risk of stroke. We tested the hypothesis that reversal of SDB in CHF patients using adaptive servo ventilation (ASV) would increase morning HCVR. DESIGN: Interventional, cross-over clinical study. SETTING: Research sleep laboratory. PATIENTS: Ten CHF patients with SDB, predominantly obstructive sleep apnea. INTERVENTIONS: The HCVR was measured from the change in middle cerebral artery velocity, using pulsed Doppler ultrasound. HCVR was determined during the evening (before) and morning (after) 1 night of sleep on ASV and 1 night of spontaneous sleep (control). MEASUREMENTS AND RESULTS: Compared with the control situation, ASV decreased the apnea-hypopnea index (group mean +/- SEM, control: 48 +/- 12, ASV: 4 +/- 1 events per hour). HCVR was 23% lower in the morning, compared with the evening, on the control night (evening: 1.3 +/- 0.2, morning: 1.0 +/- 0.2 cm/sec per mm Hg, P < 0.05) and 27% lower following the ASV night (evening: 1.5 +/- 0.2, morning: 1.1 +/- 0.2 cm/sec per mm Hg, P < 0.05). The effect of ASV on the evening-to-morning reduction in HCVR was not significant, compared with the control night (0.02 cm/sec per mm Hg, 95% confidence interval: -0.28, 0.32 P = 0.89). CONCLUSIONS: In CHF patients with SDB, HCVR was reduced in the morning compared with the evening. However, removal of SDB for 1 night did not reverse the reduced HCVR. The relatively low morning HCVR could be linked with an increased risk of stroke. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17552381&query_hl=1 ER - TY - JFULL T1 - The relation of adult bronchial responsiveness to serious childhood respiratory illness in the ECRHS. A1 - Chinn, S A1 - Janson, C A1 - Svanes, C A1 - Dharmage, S A1 - Jarvis, D J1 - Respir Med Y1 - 2007/05// VL - 101 SN - 0954-6111 SP - 983 EP - 988 N2 - BACKGROUND: Respiratory symptoms in adulthood have been found to be associated with childhood respiratory infection, but few studies have analyzed adult bronchial responsiveness (BHR) with adequate adjustment for known risk factors. OBJECTIVE: To estimate the relation of BHR with serious childhood respiratory infections in a large population study. METHODS: The European Community Respiratory Health Survey (ECRHS) was a cross-sectional population-based survey in 34 centers. Data on serious respiratory infections before the age of 5 years and possible confounders were obtained from a questionnaire administered in the clinic. Blood samples were taken for measurement of total immunoglobulin E (IgE) and specific IgE to four common allergens, and spirometry and bronchial challenge with methacholine were performed. A continuous measure of BHR was analyzed by multiple regression, in 11,282 participants, in relation to serious respiratory infection and other potential risk factors, adjusted for center and major determinants of adult BHR. RESULTS: Those reporting a serious childhood respiratory infection had greater BHR, by an amount corresponding to approximately 0.23 doubling doses (95% confidence interval 0.02-0.44) of the amount of methacholine causing a 20% fall (PD(20)) in forced expiratory volume in 1s (FEV(1)). All childhood factors explained less than 0.3% of variation in BHR in addition to over 20% by factors measured in adulthood. The relation of BHR to BMI was confined to smokers. CONCLUSIONS: We found an effect of serious childhood respiratory infection on adult BHR, but this was small in comparison to relations of BHR to IgE-sensitization and airway caliber. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17049442&query_hl=1 ER - TY - JFULL T1 - The role of cardiovascular magnetic resonance in patients presenting with chest pain, raised troponin, and unobstructed coronary arteries. A1 - Assomull, RG A1 - Lyne, JC A1 - Keenan, N A1 - Gulati, A A1 - Bunce, NH A1 - Davies, SW A1 - Pennell, DJ A1 - Prasad, SK J1 - Eur Heart J Y1 - 2007/05// VL - 28 SN - 0195-668X SP - 1242 EP - 1249 N2 - AIMS: Troponin measurement is used in the assessment and risk stratification of patients presenting acutely with chest pain when the main cause of elevation is coronary artery disease. However, some patients have no coronary obstruction on angiography, leading to diagnostic uncertainty. We evaluated the incremental diagnostic value of cardiovascular magnetic resonance (CMR) in these patients. METHODS AND RESULTS: Sixty consecutive patients (mean age 44 years, 72% male) with a troponin-positive episode of chest pain and unobstructed coronary arteries were recruited within 3 months of initial presentation. All patients underwent CMR with cine imaging, T2-weighted imaging for detection of inflammation, and late gadolinium enhancement imaging for detection of infarction/fibrosis. An identifiable basis for troponin elevation was established in 65% of patients. The commonest underlying cause was myocarditis (50%), followed by myocardial infarction (11.6%) and cardiomyopathy (3.4%). In the 35% of patients where no clear diagnosis was identified by CMR, significant myocardial infarction/fibrosis was excluded. CONCLUSION: CMR is a valuable adjunct to conventional investigations in a diagnostically challenging and important group of patients with troponin-positive chest pain and unobstructed coronary arteries. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17478458&query_hl=1 ER - TY - JFULL T1 - Mechanisms of virus-induced asthma exacerbations: state-of-the-art. A GA(2)LEN and InterAirways document A1 - Papadopoulos, NG A1 - Xepapadaki, P A1 - Mallia, P A1 - Brusselle, G A1 - Watelet, JB A1 - Xatzipsalti, M A1 - Foteinos, G A1 - van Drunen, CM A1 - Fokkens, WJ A1 - D'Ambrosio, C A1 - Bonini, S A1 - Bossios, A A1 - Lotvall, J A1 - van Cauwenberge, P A1 - Holgate, ST A1 - Canonica, GW A1 - Szczeklik, A A1 - Rohde, G A1 - Kimpen, J A1 - Pitkaranta, A A1 - Makela, M A1 - Chanez, P A1 - Ring, J A1 - Johnston, SL J1 - ALLERGY Y1 - 2007/05// VL - 62 SN - 0105-4538 SP - 457 EP - 470 N2 - Viral infections of the respiratory tract are the most common precipitants of acute asthma exacerbations. Exacerbations are only poorly responsive to current asthma therapies and new approaches to therapy are needed. Viruses, most frequently human rhinoviruses (RV), infect the airway epithelium, generate local and systemic immune responses, as well as neural responses, inducing inflammation and airway hyperresponsiveness. Using in vitro and in vivo experimental models the role of various proinflammatory or anti-inflammatory mediators, antiviral responses and molecular pathways that lead from infection to symptoms has been partly unravelled. In particular, mechanisms of susceptibility to viral infection have been identified and the bronchial epithelium appeared to be a key player. Nevertheless, additional understanding of the integration between the diverse elements of the antiviral response, especially in the context of allergic airway inflammation, as well as the interactions between viral infections and other stimuli that affect airway inflammation and responsiveness may lead to novel strategies in treating and/or preventing asthma exacerbations. This review presents the current knowledge and highlights areas in need of further research. ER - TY - JFULL T1 - Gut microbiota composition and development of atopic manifestations in infancy: the KOALA Birth Cohort Study. A1 - Penders, J A1 - Thijs, C A1 - van den Brandt, PA A1 - Kummeling, I A1 - Snijders, B A1 - Stelma, F A1 - Adams, H A1 - van Ree, R A1 - Stobberingh, EE J1 - Gut Y1 - 2007/05// VL - 56 SN - 0017-5749 SP - 661 EP - 667 N2 - BACKGROUND AND AIMS: Perturbations in intestinal microbiota composition due to lifestyle changes may be involved in the development of atopic diseases. We examined gut microbiota composition in early infancy and the subsequent development of atopic manifestations and sensitisation. METHODS: The faeces of 957 infants aged 1 month and participating in the KOALA Birth Cohort Study were analysed using quantitative real-time PCR. Information on atopic symptoms (eczema, wheeze) and potential confounders was acquired through repeated questionnaires. Total and specific IgE were measured in venous blood samples collected during home visits when the infant was 2 years old. During these home visits a clinical diagnosis of atopic dermatitis was made according to the UK-Working Party criteria. RESULTS: The presence of Escherichia coli was associated with a higher risk of developing eczema (OR(adj) = 1.87; 95% CI 1.15 to 3.04), this risk being increased with increasing numbers of E coli (p(for trend) = 0.016). Infants colonised with Clostridium difficile were at higher risk of developing eczema (OR(adj) = 1.40; 95% CI 1.02 to 1.91), recurrent wheeze (OR(adj) = 1.75; 95% CI 1.09 to 2.80) and allergic sensitisation (OR(adj) = 1.54; 95% CI 1.02 to 2.31). Furthermore, the presence of C difficile was also associated with a higher risk of a diagnosis of atopic dermatitis during the home visit (OR(adj) = 1.73; 95% CI 1.08 to 2.78). CONCLUSION: This study demonstrates that differences in gut microbiota composition precede the development of atopy. Since E coli was only associated with eczema and C difficile was associated with all atopic outcomes, the underlying mechanisms explaining these association may be different. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17047098&query_hl=1 ER - TY - JFULL T1 - Sepsis since the discovery of Toll-like receptors: disease concepts and therapeutic opportunities. A1 - Leaver, SK A1 - Finney, SJ A1 - Burke-Gaffney, A A1 - Evans, TW J1 - Crit Care Med Y1 - 2007/05// VL - 35 SN - 0090-3493 SP - 1404 EP - 1410 N2 - OBJECTIVE: Sepsis and its sequelae are the leading cause of death in critically ill patients. Discovery in the late 1990s of Toll-like receptors as primary sensors of microbial infection led to significant advances in understanding the pathogenesis of sepsis, including emerging differences between Gram-positive and Gram-negative infection and the potential for the manipulation of Toll-like receptors for the treatment of sepsis. This review describes these advances. METHODS: Bibliographic search of the literature since 1999, with particular emphasis on the conceptual and therapeutic implications of Toll-like receptors for patients with systemic sepsis. RESULTS AND CONCLUSIONS: Toll-like receptors initiate the inflammatory processes that underlie the clinical response to infection and therefore represent an important putative target for therapeutic intervention. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17414083&query_hl=1 ER - TY - JFULL T1 - Sudden arrhythmic death syndrome: a national survey of sudden unexplained cardiac death A1 - Behr, ER A1 - Casey, A A1 - Sheppard, M A1 - Wright, M A1 - Bowker, TJ A1 - Davies, MJ A1 - McKenna, WJ A1 - Wood, DA J1 - HEART Y1 - 2007/05// VL - 93 SN - 1355-6037 SP - 601 EP - 605 N2 - Objective: To describe the characteristics of sudden arrhythmic death syndrome (SADS) and compare its incidence with official national mortality statistics for unascertained deaths.Design and setting: Sudden unexplained deaths were prospectively surveyed through 117 coroners' jurisdictions in England. Consecutive cases meeting the following criteria were included: white Caucasian, aged 4-64 years, no history of cardiac disease, last seen alive within 12 h of death, normal coroner's autopsy, cardiac pathologist's confirmation of a normal heart and negative toxicology.Main outcome measures: The estimated mortality from SADS was calculated and the official mortality statistics for unascertained causes of deaths in 4-64-year-olds was identified for the same time period.Results: 115 coroner's cases were reported and 56 (49%) SADS victims were identified: mean age 32 years, range 7-64 years and 35 (63%) male. 7 of 39 cases (18%) had a family history of other premature sudden deaths (, 45). The estimated mortality from SADS was 0.16/100000 per annum (95% CI 0.12 to 0.21), compared with an official mortality of 0.10/ 100 000 per annum for International Classification of Diseases 798.1 (sudden death, cause unknown-instantaneous death) or 1.34/100000 per annum for unascertained causes of death.Conclusions: Deaths from SADS occur predominantly in young males. When compared with official mortality, the incidence of SADS may be up to eight times higher than estimated: more than 500 potential SADS cases per annum in England. Families with SADS carry genetic cardiac disease, placing them at risk of further sudden deaths. SADS should therefore be a certifiable cause of death prompting specialised cardiological evaluation of families. ER - TY - JFULL T1 - T lymphocyte rolling and recruitment into peripheral lymph nodes is regulated by a saturable density of L-selectin (CD62L). A1 - Galkina, E A1 - Florey, O A1 - Zarbock, A A1 - Smith, BR A1 - Preece, G A1 - Lawrence, MB A1 - Haskard, DO A1 - Ager, A J1 - Eur J Immunol Y1 - 2007/05// VL - 37 SN - 0014-2980 SP - 1243 EP - 1253 N2 - L-selectin mediates tethering and rolling of lymphocytes in high endothelial venules (HEV) of lymph nodes (LN) and of leukocytes at inflammatory sites. We used transgenic mice expressing varying levels of wild-type or a non-cleavable mutant form of L-selectin on T cells to determine the relationship between L-selectin density, tethering and rolling, and migration into LN. T cells expressing supraphysiological levels of either wild-type or non-cleavable L-selectin showed rolling parameters similar to C57BL/6 T cells in hydrodynamic flow assays and during rolling in Peyer's patch HEV. In contrast, PMA- or antigen-activated T cells and L-selectin(+/-) T cells expressing subphysiological levels of L-selectin showed reduced numbers of rolling cells with increased rolling velocity. Short-term homing studies showed that elevated expression of L-selectin above physiological levels had no effect on T cell migration to LN; however, low L-selectin expression resulted in reduced T cell homing to LN. Thus, T lymphocyte migration into LN is regulated by the density of cell surface L-selectin. In addition, there is a saturable density of L-selectin required for optimal homing to PLN in C57BL/6 mice, the L-selectin level on circulating naive T cells promotes optimal homing, and increased expression above saturating levels promotes no further increase in T cell recruitment. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17429841&query_hl=1 ER - TY - JFULL T1 - Remodeling and airway hyperresponsiveness but not cellular inflammation persist after allergen challenge in asthma. A1 - Kariyawasam, HH A1 - Aizen, M A1 - Barkans, J A1 - Robinson, DS A1 - Kay, AB J1 - Am J Respir Crit Care Med Y1 - 2007/05/01/ VL - 175 SN - 1073-449X SP - 896 EP - 904 N2 - RATIONALE: Airway hyperresponsiveness (AHR) increases up to 2 weeks after allergen inhalational challenge of subjects with asthma who show a late-phase asthmatic reaction (dual responders). Cellular inflammation and airway remodeling are increased 24 hours after allergen challenge. OBJECTIVES: To determine whether persistence of increased AHR is associated with persistent activation of remodeling and enhanced inflammation. METHODS: Fiberoptic bronchoscopy was performed at baseline and at 24 hours and 7 days after allergen inhalational challenge of dual responders with mild-moderate asthma. At each time point, AHR, spirometry, and expression of tenascin (extracellular matrix protein), procollagen I, procollagen III, and heat shock protein (HSP)-47 (markers of collagen synthesis), and alpha-smooth muscle actin (myofibroblasts) were evaluated as markers of activation of airway remodeling, together with numbers of mucosal major basic protein-positive eosinophils, CD68(+) macrophages, CD3(+), CD4(+), CD8(+) T cells, elastase-positive neutrophils, and tryptase-positive mast cells. MEASUREMENTS AND MAIN RESULTS: AHR was increased from baseline at 24 hours and 7 days after allergen challenge. Reticular basement membrane tenascin expression was elevated at 24 hours and returned to baseline levels at 7 days. Reticular basement membrane procollagen III expression was significantly elevated at 7 days. Expression of procollagen I, HSP-47, and alpha-smooth muscle actin were all higher at 7 days compared with 24 hours. At 24 hours, eosinophil, macrophage, neutrophil, and CD3(+) T cells were increased but had returned to baseline by 7 days. CONCLUSIONS: In dual responders with asthma, the 24-hour increase in airway wall cellular inflammation after allergen challenge resolves by 7 days, whereas the increases in AHR and markers of remodeling persist. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17272787&query_hl=1 ER - TY - JFULL T1 - Airway expression of calcitonin gene-related peptide in T-cell peptide-induced late asthmatic reactions in atopics. A1 - Kay, AB A1 - Ali, FR A1 - Heaney, LG A1 - Benyahia, F A1 - Soh, CP A1 - Renz, H A1 - Lee, TH A1 - Larché, M J1 - Allergy Y1 - 2007/05// VL - 62 SN - 0105-4538 SP - 495 EP - 503 N2 - BACKGROUND: The mechanisms of late asthmatic reactions provoked in atopic asthmatics by allergen-derived T-cell peptide epitopes remain unclear. Previous studies showed no changes in airway eosinophils or mast cell products after peptide challenge. In the present study our aim was to measure calcitonin gene-related peptide (CGRP), neurokinin (NK)-A, and substance P (SP) in bronchoalveolar lavage fluid and bronchial biopsies (BB) after inhalation of allergen-derived T-cell peptide epitopes since these neuropeptides (NP) had not previously been evaluated in this chronic asthma model. METHODS: Bronchoscopy, with BB and bronchoalveolar lavage (BAL), was performed in 24 cat-allergic subjects 6 h after inhalation of Fel d 1-derived peptides. Neuropeptides were measured in BAL by enzyme-linked immunosorbent assay and CGRP expression in the airways was assessed by immunohistochemistry and confocal microscopy. RESULTS: Twelve subjects (termed 'responders') developed isolated late reactions. Calcitonin gene-related peptide, but not NK-A or SP, was significantly elevated in BAL in responders only. Biopsy studies showed that in virtually all responders peptide challenge induced marked increases in CGRP immunoreactivity in bronchial epithelial cells, infiltrating submucosal cells and in association with airway smooth muscle. Double immunostaining indicated that CGRP colocalized predominantly to CD3+/CD4+ and CD68+ submucosal inflammatory cells. CONCLUSION: Calcitonin gene-related peptide, a potent vasodilator, is markedly up-regulated in the airways of atopic asthmatics during late-phase reactions provoked by inhalation of allergen-derived T-cell peptides. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17441790&query_hl=1 ER - TY - JFULL T1 - Hyperglycemia and cystic fibrosis alter respiratory fluid glucose concentrations estimated by breath condensate analysis A1 - Baker, EH A1 - Clark, N A1 - Brennan, AL A1 - Fisher, DA A1 - Gyi, KM A1 - Hodson, ME A1 - Philips, BJ A1 - Baines, DL A1 - Wood, DM J1 - J APPL PHYSIOL Y1 - 2007/05// VL - 102 SN - 8750-7587 SP - 1969 EP - 1975 N2 - In animals, glucose concentrations are 3-20 times lower in lung lining fluid than in plasma. In humans, glucose concentrations are normally low (< 1 mmol/l) in nasal and bronchial fluid, but they are elevated by inflammation or hyperglycemia. Furthermore, elevated bronchial glucose is associated with increased respiratory infection in intensive care patients. Our aims were to estimate normal glucose concentrations in fluid from distal human lung sampled noninvasively and to determine effects of hyperglycemia and lung disease on lung glucose concentrations. Respiratory fluid was sampled as exhaled breath condensate, and glucose was measured by chromatography with pulsed amperometric detection. Dilution corrections, based on conductivity, were applied to estimate respiratory fluid glucose concentrations (breath glucose). We found that breath glucose in healthy volunteers was 0.40 mmol/l (SD 0.24), reproducible, and unaffected by changes in salivary glucose. Breath-to-blood glucose ratio (BBGR) was 0.08 (SD 0.05). Breath glucose increased during experimental hyperglycemia (P < 0.05) and was elevated in diabetic patients without lung disease [1.20 mmol/l (SD 0.69)] in proportion to hyperglycemia [BBGR 0.09 (SD 0.06)]. Breath glucose was elevated more than expected for blood glucose in cystic fibrosis patients [breath 2.04 mmol/l (SD 1.14), BBGR 0.29 (SD 0.17)] and in cystic fibrosis-related diabetes [breath 4.00 mmol/l (SD 2.07), BBGR 0.54 (0.28); P < 0.0001]. These data indicate- that 1) this method makes a biologically plausible estimate of respiratory fluid glucose concentration, 2) respiratory fluid glucose concentrations are elevated by hyperglycemia and lung disease, and 3) effects of hyperglycemia and lung disease can be distinguished using the BBGR. This method will support future in vivo investigation of the cause and effect of elevated respiratory fluid glucose in human lung disease. ER - TY - JFULL T1 - Direct intramyocardial but not intracoronary injection of bone marrow cells induces ventricular arrhythmias in a rat chronic ischemic heart failure model. A1 - Fukushima, S A1 - Varela-Carver, A A1 - Coppen, SR A1 - Yamahara, K A1 - Felkin, LE A1 - Lee, J A1 - Barton, PJ A1 - Terracciano, CM A1 - Yacoub, MH A1 - Suzuki, K J1 - Circulation Y1 - 2007/05/01/ VL - 115 SN - 1524-4539 SP - 2254 EP - 2261 N2 - BACKGROUND: Therapeutic efficacy of bone marrow (BM) cell injection for treating ischemic chronic heart failure has not been established. In addition, experimental data are lacking on arrhythmia occurrence after BM cell injection. We hypothesized that therapeutic efficacy and arrhythmia occurrence induced by BM cell injection may be affected by the cell delivery route. METHODS AND RESULTS: Three weeks after left coronary artery ligation, wild-type female rats were injected with 1x10(7) mononuclear BM cells derived from green fluorescent protein-transgenic male rats through either a direct intramyocardial or a retrograde intracoronary route. Both intramyocardial and intracoronary injection of BM cells demonstrated similar improvement in left ventricular ejection fraction measured by echocardiography and a similar graft size analyzed by real-time polymerase chain reaction for the Y chromosome-specific Sry gene. Noticeably, intramyocardial injection of BM cells induced frequent ventricular premature contractions (108+/-73 per hour at 7 days after BM cell injection), including multiform, consecutive ventricular premature contractions and ventricular tachycardia for the initial 14 days; intracoronary injection of BM cells and intramyocardial injection of phosphate-buffered saline rarely induced arrhythmias. Immunohistochemistry demonstrated that intramyocardial BM cell injection formed distinct cell clusters containing donor-derived cells and accumulated host-derived inflammatory cells in the infarct border zone, whereas intracoronary BM cell injection provided more homogeneous donor cell dissemination with less inflammation and without disrupting the native myocardial structure. CONCLUSIONS: BM cell injection is able to improve cardiac function in ischemic chronic heart failure but has a risk of arrhythmia occurrence when the intramyocardial route is used. Such arrhythmias may be prevented by using the intracoronary route. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17438152&query_hl=1 ER - TY - JFULL T1 - Assessing normal pulse wave velocity in the proximal pulmonary arteries using transit time: a feasibility, repeatability, and observer reproducibility study by cardiovascular magnetic resonance. A1 - Bradlow, WM A1 - Gatehouse, PD A1 - Hughes, RL A1 - O'Brien, AB A1 - Gibbs, JS A1 - Firmin, DN A1 - Mohiaddin, RH J1 - J Magn Reson Imaging Y1 - 2007/05// VL - 25 SN - 1053-1807 SP - 974 EP - 981 N2 - PURPOSE: To calculate pulse wave velocity (PWV) in the proximal pulmonary arteries (PAs) by cardiovascular magnetic resonance (CMR) using the transit-time method, and address respiratory variation, repeatability, and observer reproducibility. MATERIALS AND METHODS: A 1.9-msec interleaved phase velocity sequence was repeated three times consecutively in 10 normal subjects. Pulse wave (PW) arrival times (ATs) were determined for the main and branch PAs. The PWV was calculated by dividing the path length traveled by the difference in ATs. Respiratory variation was considered by comparing acquisitions with and without respiratory gating. RESULTS: For navigated data the mean PWVs for the left PA (LPA) and right PA (RPA) were 2.09 +/- 0.64 m/second and 2.33 +/- 0.44 m/second, respectively. For non-navigated data the mean PWVs for the LPA and RPA were 2.14 +/- 0.41 m/second and 2.31 +/- 0.49 m/second, respectively. No statistically significant difference was found between respiratory non-navigated data and navigated data. Repeated on-table measurements were consistent (LPA non-navigated P = 0.95, RPA non-navigated P = 0.91, LPA navigated P = 0.96, RPA navigated P = 0.51). The coefficients of variation (CVs) were 12.2% and 12.5% for intra- and interobserver assessments, respectively. CONCLUSION: One can measure PWV in the proximal PAs using transit-time in a reproducible manner without respiratory gating. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17457797&query_hl=1 ER - TY - JFULL T1 - Lung fibrosis as a potential complication of the hemostatic tissue sealant, biologic glue (Bioglue). A1 - Haj-Yahia, S A1 - Mittal, T A1 - Birks, E A1 - Carby, M A1 - Petrou, M A1 - Pepper, J A1 - Dreyfus, G A1 - Amrani, M J1 - J Thorac Cardiovasc Surg Y1 - 2007/05// VL - 133 SN - 1097-685X SP - 1387 EP - 1388 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17467473&query_hl=1 ER - TY - JFULL T1 - Safety and efficacy concerns regarding elective coronary artery surgery in patients with prior coronary stents A1 - Chikwe, J A1 - Athanasiou, T A1 - Collins, P A1 - Pepper, JR J1 - EUR HEART J Y1 - 2007/05// VL - 28 SN - 0195-668X SP - 1265 EP - 1265 ER - TY - JFULL T1 - The role of antibiotics in asthma A1 - Blasi, F A1 - Johnston, SL J1 - INT J ANTIMICROB AG Y1 - 2007/05// VL - 29 SN - 0924-8579 SP - 485 EP - 493 N2 - There is increasing evidence that atypical respiratory pathogens such as Chlamydophila pneumoniae and Mycoplasma pneumoniae may contribute to the pathogenesis of both stable asthma and asthma exacerbations. It is postulated that these organisms may contribute to inflammation in the airways possibly by activating inflammatory mechanisms in the respiratory tract.The macrolide class of antibiotics may have a part to play in the management of asthma by exerting anti-inflammatory effects on the chronically inflamed airways in addition to their anti-infective action. The ketolide antibiotics may also have similar properties.This paper discusses the role of these antibiotics in the management of asthma. (C) 2006 Elsevier B.V and the International Society of Chemotherapy. All rights reserved. ER - TY - JFULL T1 - Chronic obstructive pulmonary disease: a growing but neglected global epidemic. A1 - Barnes, PJ J1 - PLoS Med Y1 - 2007/05// VL - 4 SN - 1549-1676 SP - e112 EP - e112 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17503959&query_hl=1 ER - TY - JFULL T1 - New molecular targets for the treatment of neutrophilic diseases. A1 - Barnes, PJ J1 - J Allergy Clin Immunol Y1 - 2007/05// VL - 119 SN - 0091-6749 N2 - Increased neutrophils are a feature of airway inflammation in patients with chronic obstructive pulmonary disease and in some patients with asthma, particularly patients with more severe disease, during exacerbations and with cigarette smoking. Because neutrophilic inflammation may be detrimental, there are several new approaches to inhibiting neutrophilic inflammation. Neutrophilic inflammation is resistant or poorly responsive to corticosteroids, so different anti-inflammatory approaches are needed. Blocking neutrophil chemotactic factors such as leukotriene B(4) and IL-8 and related cysteine-X-cysteine chemokines by blocking receptor for leukotriene B(4) 1 and receptor for cysteine-X-cysteine chemokines 2 receptors is an approach that is currently being investigated. Other approaches include blocking adhesion molecules such as E-selectin. Inhibiting phosphodiesterase-4, nuclear factor-kappaB, or p38 mitogen-activated protein kinase is another approach that inhibits the production of cysteine-X-cysteine chemokines. Antioxidants, long-acting beta(2)-agonists, and activators of histone deacetylase may also be effective. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17353033&query_hl=1 ER - TY - JFULL T1 - Chemical respiratory allergy: Opportunities for hazard identification and characterisation - The report and recommendations of ECVAM workshop 60(a) A1 - Kimber, I A1 - Agius, R A1 - Basketter, DA A1 - Corsini, E A1 - Cullinan, P A1 - Dearman, RJ A1 - Gimenez-Arnau, E A1 - Greenwell, L A1 - Hartung, T A1 - Kuper, F A1 - Maestrelli, P A1 - Roggen, E A1 - Rovida, C J1 - ATLA-ALTERN LAB ANIM Y1 - 2007/05// VL - 35 SN - 0261-1929 SP - 243 EP - 265 N2 - This is the 60th Report of a series of workshops organised by the European Centre for the validation of Alternative Methods (ECVAM). The main goal of ECVAM, as defined in 1993 by its Scientific Advisory Committee, is to promote the scientific relevance and that reduce, refine or replace the use of laboratory animals. One of the first measures taken by ECVAM was the implementation of procedures that would enable it to become better informed about the state-of-the-art of non-animal test development and validation, and the potential for the possible incorporation of alternatives tests into regulatory procedures. The decision was taken that this would be best achieved by the organisation of ECVAM Workshops each addressing a specific topic, and at which selected groups of independent international experts would review the status of various types of in vitro tests and their potential application, and make recommendations about the best way forward.A workshop on Chemical Respiratory Allergy, chaired by Ian Kimber, was held at ECVAM from 11-13 October 2006.Chemical respiratory allergy, typically associated with rhinitis and/or asthma, is considered to be an adverse health effect of high concern. FOr example, under the EU Registration, Evaluation and Authorisation of Chemicals (REACH) system, respiratory sensitisers are included among substances of higher risk, together with CMRs (chemicals that are Carcinogenic, Mutagenic or toxic for Reproduction), and are regulated under Annex 1 of Directive 67/548/EEC, which contains a list of dangerous substances, including respiratory sensitisers. Although some animal methods (such as measurements of IgE antibody responses in mice or specific pulmonary reactions in guinea-pigs) are mentioned in this Directive, these have not been validated, nor are they widely accepted by the scientific community.At present, chemical respiratory sensitisation hazard is assigned to chemicals on the basis of epidemiological evidence or, in the case of diisocyanates, as a default classification. Therefore, there is clearly a need to develop new and improved methods for hazard identification and characterisation, and it was the objective of this workshop to explore what opportunities might now be available. ER - TY - JFULL T1 - Eosinophils in the pathogenesis of allergic airways disease. A1 - Trivedi, SG A1 - Lloyd, CM J1 - Cell Mol Life Sci Y1 - 2007/05// VL - 64 SN - 1420-682X SP - 1269 EP - 1289 N2 - Eosinophils are traditionally thought to form part of the innate immune response against parasitic helminths acting through the release of cytotoxic granule proteins. However, they are also a central feature in asthma. From their development in the bone marrow to their recruitment to the lung via chemokines and cytokines, they form an important component of the inflammatory milieu observed in the asthmatic lung following allergen challenge. A wealth of studies has been performed in both patients with asthma and in mouse models of allergic pulmonary inflammation to delineate the role of eosinophils in the allergic response. Although the long-standing association between eosinophils and the induction of airway hyper-responsiveness remains controversial, recent studies have shown that eosinophils may also promote airway remodelling. In addition, emerging evidence suggests that the eosinophil may also serve to modulate the immune response. Here we review the highly co-ordinated nature of eosinophil development and trafficking and the evolution of the eosinophil as a multi-factoral leukocyte with diverse functions in asthma. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17364144&query_hl=1 ER - TY - JFULL T1 - Use of ultrasound to enhance nonviral lung gene transfer in vivo. A1 - Xenariou, S A1 - Griesenbach, U A1 - Liang, HD A1 - Zhu, J A1 - Farley, R A1 - Somerton, L A1 - Singh, C A1 - Jeffery, PK A1 - Ferrari, S A1 - Scheule, RK A1 - Cheng, SH A1 - Geddes, DM A1 - Blomley, M A1 - Alton, EW J1 - Gene Ther Y1 - 2007/05// VL - 14 SN - 0969-7128 SP - 768 EP - 774 N2 - We have assessed if high-frequency ultrasound (US) can enhance nonviral gene transfer to the mouse lung. Cationic lipid GL67/pDNA, polyethylenimine (PEI)/pDNA and naked plasmid DNA (pDNA) were delivered via intranasal instillation, mixed with Optison microbubbles, and the animals were then exposed to 1 MHz US. Addition of Optison alone significantly reduced the transfection efficiency of all three gene transfer agents. US exposure did not increase GL67/pDNA or PEI/pDNA gene transfer compared to Optison-treated animals. However, it increased naked pDNA transfection efficiency by approximately 15-fold compared to Optison-treated animals, suggesting that despite ultrasound being attenuated by air in the lung, sufficient energy penetrates the tissue to increase gene transfer. US-induced lung haemorrhage, assessed histologically, increased with prolonged US exposure. The left lung was more affected than the right and this was mirrored by a lesser increase in naked pDNA gene transfer, in the left lung. The positive effect of US was dependent on Optison, as in its absence US did not increase naked pDNA transfection efficiency. We have thus established proof of principle that US can increase nonviral gene transfer, in the air-filled murine lung. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17301842&query_hl=1 ER - TY - JFULL T1 - Quantification of the effects of a ryanodine receptor channel mutation on interaction with a ryanoid. A1 - Ranatunga, KM A1 - Chen, SR A1 - Ruest, L A1 - Welch, W A1 - Williams, AJ J1 - Mol Membr Biol Y1 - 2007/05// VL - 24 SN - 0968-7688 SP - 185 EP - 193 N2 - Understanding the nature of the interaction of the plant alkaloid ryanodine with its receptor channel (RyR) is important to aid interpretation of physiological studies and provide structure-function information about RyR. We present here the first quantitative description of the relative single-channel kinetic effects of a single-point mutation in RyR2. We exploit the well-characterized ryanoid 8beta-amino-9alpha-hydroxyryanodine that displays reversible kinetics with RyR2. We explicitly show that the effect of the Q4863A mutation is to increase the apparent dissociation constant by increasing the apparent dissociation rate of the ryanoid. The voltage-dependence of the interaction displays no change. We infer that Q4863 is not involved with the voltage-drop but is able to influence ryanoid-bound structural changes. We discuss structural mechanisms by which this mutation could affect ryanoid interaction. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17520475&query_hl=1 ER - TY - JFULL T1 - Allergen-induced airway remodelling. A1 - Lloyd, CM A1 - Robinson, DS J1 - Eur Respir J Y1 - 2007/05// VL - 29 SN - 0903-1936 SP - 1020 EP - 1032 N2 - Airway remodelling is associated with chronic asthma but it remains unclear whether it results from airway inflammation in response to allergens or immune-mediated events such as viral infections. Although the acute inflammation associated with asthma has been modelled extensively both in vitro and in vivo, the structural changes occurring in the lung have only recently been investigated. These in vitro, in vivo and in silico systems have been designed to examine the pathways leading to allergen-induced airway remodelling and have enabled investigators to draw conclusions about the participation of key cells and molecules in the development of allergen-induced airway remodelling. However, fundamental questions remain regarding the genesis of remodelling as well as the relationship between functional symptoms and pathological changes that occur. In this review the key questions relating allergen exposure to development of remodelling are discussed, as well as the steps that are being undertaken to investigate them. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17470623&query_hl=1 ER - TY - JFULL T1 - The role of statins in vascular protection. A1 - Mason, JC J1 - Clin Adv Hematol Oncol Y1 - 2007/05// VL - 5 SN - 1543-0790 SP - 352 EP - 354 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17673889&query_hl=1 ER - TY - JFULL T1 - Critical role for lipid raft-associated Src kinases in activation of PI3K-Akt signalling. A1 - Arcaro, A A1 - Aubert, M A1 - Espinosa del Hierro, ME A1 - Khanzada, UK A1 - Angelidou, S A1 - Tetley, TD A1 - Bittermann, AG A1 - Frame, MC A1 - Seckl, MJ J1 - Cell Signal Y1 - 2007/05// VL - 19 SN - 0898-6568 SP - 1081 EP - 1092 N2 - Lipid rafts are membrane microdomains distinct from caveolae, whose functions in polypeptide growth factor signalling remain unclear. Here we show that in small cell lung cancer (SCLC) cells, specific growth factor receptors such as c-Kit associate with lipid rafts and that these domains play a critical role in the activation of phosphoinositide 3-kinase (PI3K) signalling. The class IA p85/p110alpha associated with Src in lipid rafts and was activated by Src in vitro. Lipid raft integrity was essential for Src activation in response to stem cell factor (SCF) and raft disruption selectively inhibited activation of protein kinase B (PKB)/Akt in response to SCF stimulation. Moreover, inhibition of Src kinases blocked PKB/Akt activation and SCLC cell growth. The use of fibroblasts with targeted deletion of the Src family kinase genes confirmed the role of Src kinases in PKB/Akt activation by growth factor receptors. Moreover a constitutively activated mutant of Src also stimulated PI3K/Akt in lipid rafts, indicating that these microdomains play a role in oncogenic signalling. Together our data demonstrate that lipid rafts play a key role in the activation of PI3K signalling by facilitating the interaction of Src with specific PI3K isoforms. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17275257&query_hl=1 ER - TY - JFULL T1 - Number of allergens to be tested to assess allergenic sensitization in epidemiologic studies: results of the European Community Respiratory Health Survey I. A1 - Bousquet, PJ A1 - Hooper, R A1 - Kogevinas, M A1 - Jarvis, D A1 - Burney, P J1 - Clin Exp Allergy Y1 - 2007/05// VL - 37 SN - 0954-7894 SP - 780 EP - 787 N2 - BACKGROUND: Many clinical and epidemiological studies have measured the prevalence of IgE sensitization using skin tests and/or serum-specific IgE. Most of them have been done in only one country using a battery of selected allergens relevant to that country. In multi-centre studies, the number of tested allergens is often limited by the cost. It is therefore difficult to compare prevalence of sensitized subjects between studies. OBJECTIVE: To define the number and the type of allergen that should be tested in order to characterize a person as sensitized. METHOD: Subjects were selected from the European Community Respiratory Health Survey I. All subjects underwent skin prick tests to nine of the most common allergens. In addition, two local allergens were tested in some centres. RESULT: Using nine allergens, 35.6% of the 11 355 subjects were sensitized. The prevalence of sensitization increased with the number of tested allergens. Seven allergens enabled the identification of almost all sensitized subjects, adding another one inducing, in most countries, an increase of prevalence under 0.5%. Adding one local allergen to the battery of tests increased the overall estimated prevalence by only 1%. This increase was not seen in Ireland and was less marked in the United Kingdom (0.3%) but was greater in France (2.6%), Australia (2.5%) and Belgium (1.9%). CONCLUSION: Seven selected allergens (Dermatophagoides pteronyssinus, cat, grass, birch, olive pollen, Alternaria and Cladosporium) allow the identification of almost all sensitized subjects in epidemiologic studies. Inclusion of local allergen should be considered in a standard panel for international studies. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17456226&query_hl=1 ER - TY - JFULL T1 - Physical activity and bronchial hyperresponsiveness: European Community Respiratory Health Survey II. A1 - Shaaban, R A1 - Leynaert, B A1 - Soussan, D A1 - Antó, JM A1 - Chinn, S A1 - de Marco, R A1 - Garcia-Aymerich, J A1 - Heinrich, J A1 - Janson, C A1 - Jarvis, D A1 - Sunyer, J A1 - Svanes, C A1 - Wjst, M A1 - Burney, PG A1 - Neukirch, F A1 - Zureik, M J1 - Thorax Y1 - 2007/05// VL - 62 SN - 0040-6376 SP - 403 EP - 410 N2 - BACKGROUND: Identification of the risk factors for bronchial hyperresponsiveness (BHR) would increase the understanding of the causes of asthma. The relationship between physical activity and BHR in men and women aged 28.0-56.5 years randomly selected from 24 centres in 11 countries participating in the European Community Respiratory Health Survey II was investigated. METHODS: 5158 subjects answered questionnaires about physical activity and performed BHR tests. Participants were asked about the frequency and duration of usual weekly exercise resulting in breathlessness or sweating. BHR was defined as a decrease in forced expiratory volume in 1 s of at least 20% of its post-saline value for a maximum methacholine dose of 2 mg. RESULTS: Both frequency and duration of physical activity were inversely related to BHR. The prevalence of BHR in subjects exercising or=4 times a week was 14.5%, 11.6% and 10.9%, respectively (p<0.001). The corresponding odds ratios were 1.00, 0.78 (95% CI 0.62 to 0.99) and 0.69 (95% CI 0.50 to 0.94) after controlling for potential confounding factors. The frequency of BHR in subjects exercising <1 h, 1-3 h and >or=4 h a week was 15.9%, 10.9% and 10.7%, respectively (p<0.001). The corresponding adjusted odds ratios were 1.00, 0.70 (95% CI 0.57 to 0.87) and 0.67 (95% CI 0.50 to 0.90). Physical activity was associated with BHR in all studied subgroups. CONCLUSIONS: These results suggest that BHR is strongly and independently associated with decreased physical activity. Further studies are needed to determine the mechanisms underlying this association. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17121869&query_hl=1 ER - TY - JFULL T1 - Socioeconomic status, asthma and chronic bronchitis in a large community-based study A1 - Ellison-Loschmann, L A1 - Sunyer, J A1 - Plana, E A1 - Pearce, N A1 - Zock, JP A1 - Jarvis, D A1 - Janson, C A1 - Anto, JM A1 - Kogevinas, M A1 - European Community Resp Hlth Surve J1 - EUR RESPIR J Y1 - 2007/05// VL - 29 SN - 0903-1936 SP - 897 EP - 905 N2 - The present study investigated the relationship between socioeconomic status, using measures of occupational class and education level, and the prevalence and incidence of asthma (with and without atopy) and chronic bronchitis using data from the European Community Respiratory Health Survey (ECRHS).Asthma and chronic bronchitis were studied prospectively within the ECRHS (n=9,023). Incidence analyses comprised subjects with no history of asthma or bronchitis at baseline. Asthma symptoms were also assessed as a continuous score.Bronchitis risk was associated with low educational level (prevalence odds ratio (POR) 1.9; 95% confidence interval (CI) 1.4-2.8) and occupational class (1.8; 1.2-2.7). Incident bronchitis also increased with low educational level (risk ratio (RR) 2.8; 95%CI 1.5-5.4). Prevalent and incident asthma with no atopy were associated with low educational level. Subjects in the low occupational class (incident risk ratio (IRR) 1.4; 95%CI 1.2-1.7) and education group (IRR 1.3; 95% CI 1.1-1.6) had higher mean asthma scores than those in higher socioeconomic groups.Lower educational level was associated with increased risk of prevalent and incident chronic bronchitis and asthma with no atopy. Lower socioeconomic groups tended to have a higher prevalence and incidence of asthma, particularly higher mean asthma scores. Adjustment for variables associated with asthma and bronchitis explained little of the observed health differences by socioeconomic status. ER - TY - JFULL T1 - Repression of inflammatory gene expression in human pulmonary epithelial cells by small-molecule IkappaB kinase inhibitors. A1 - Newton, R A1 - Holden, NS A1 - Catley, MC A1 - Oyelusi, W A1 - Leigh, R A1 - Proud, D A1 - Barnes, PJ J1 - J Pharmacol Exp Ther Y1 - 2007/05// VL - 321 SN - 0022-3565 SP - 734 EP - 742 N2 - The airway epithelium is critical in the pathogenesis of chronic inflammatory diseases, such as asthma and chronic obstructive pulmonary disease, and, by expressing numerous inflammatory genes, plays a prominent role in disease exacerbations. Since inflammatory gene expression often involves the transcription factor nuclear factor (NF)-kappaB, this signaling pathway represents a site for anti-inflammatory intervention. As the airway epithelium is targeted by inhaled therapeutic agents, for example corticosteroids, human A549 pulmonary cells and primary human bronchial epithelial (HBE) cells were selected to evaluate inhibitor of kappaB kinase (IKK) inhibitors. In A549 cells, interleukin (IL)-1beta and tumor necrosis factor (TNF) alpha increased phosphorylation of IkappaBalpha, and this was followed by loss of IkappaBalpha, induction of NF-kappaB DNA binding, and the induction of NF-kappaB-dependent transcription. These events were repressed by the IKK-selective inhibitors, PS-1145 [N-(6-chloro-9H-beta-carbolin-8-ly) nicotinamide] and ML120B [N-(6-chloro-7-methoxy-9H-beta-carbolin-8-yl)-2-methyl-nicotinamide]. Inhibition of NF-kappaB-dependent transcription was concentration-dependent and correlated with loss of intercellular adhesion molecule (ICAM)-1 expression. Similarly, IL-1beta- and TNFalpha-induced expression of IL-6, IL-8, granulocyte macrophage-colony-stimulating factor (GM-CSF), regulated and activation normal T cell expressed and secreted (RANTES), growth-related oncogene alpha, and monocyte chemotactic protein-1 (MCP-1) was also significantly repressed. Likewise, PS-1145 and ML120B profoundly reduced NF-kappaB-dependent transcription induced by IL-1beta and TNFalpha in primary HBE cells. Parallel effects on ICAM-1 expression and a significant repression of IL-8 release were observed. In contrast, the corticosteroid, dexamethasone, was without effect on NF-kappaB-dependent transcription or the expression of ICAM-1. The above data provide strong support for an anti-inflammatory effect of IKK2 inhibitors acting on the pulmonary epithelium and suggest that such compounds may prove beneficial in situations where traditional corticosteroid therapies prove inadequate. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17322026&query_hl=1 ER - TY - JFULL T1 - Retrospective study of pulmonary hypertensive patients: is right ventricular myocardial performance index a vital prognostic factor? A1 - Grapsa, I A1 - Pavlopoulos, H A1 - Dawson, D A1 - Gibbs, JS A1 - Nihoyannopoulos, P J1 - Hellenic J Cardiol Y1 - 2007/05// VL - 48 SN - 1109-9666 SP - 152 EP - 160 N2 - INTRODUCTION: Right ventricular function is a determinant of prognosis and survival in patients with pulmonary hypertension. The pulmonary hypertensive right ventricle has a complex shape. Transthoracic two-dimensional echocardiography is the primary examination for demonstrating right ventricular impairment. Nowadays, many indices have been linked with pulmonary hypertension. The myocardial performance index (MPI), which may be determined by both conventional Doppler and tissue Doppler imaging (TDI), is one of these. METHODS: Ninety-three patients with pulmonary hypertension were examined retrospectively over 3 years' treatment. The relationship between MPI and right ventricular impairment was studied, as well as the correlation with various echocardiographic determinants. In addition, we examined the correlation between conventional echocardiography and tissue Doppler imaging with reference to the MPI. RESULTS: MPI had a statistically significant relationship with the visual estimation of right ventricular impairment (r = 0.714, p = 0.001), the degree of pulmonary regurgitation (r = 0.155, p = 0.048), left ventricular eccentricity index (r = 0.299, p = 0.001 in systole) and the presence of pericardial effusion (r = 0.199, p = 0.008), while it was inversely correlated with left ventricular fractional shortening (r = -0.284, p = 0.001). However, the index had no correlation with tricuspid regurgitant velocity, right ventricular acceleration time or right atrial volume. There was significant agreement between the MPI measured by conventional Doppler echocardiography and by TDI (r = 0.83, p < 0.001; mean value -0.10, SD 0.2). Finally, some patients showed a significant decrease in tricuspid regurgitant velocity and MPI during their treatment. CONCLUSION: Right ventricular MPI has a good correlation with several parameters and can be a good prognostic factor for right ventricular impairment in patients with pulmonary hypertension. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17629178&query_hl=1 ER - TY - JFULL T1 - Detection of antibodies to Pseudomonas aeruginosa in serum and oral fluid from patients with cystic fibrosis A1 - Weisner, AM A1 - Chart, H A1 - Bush, A A1 - Davies, JC A1 - Pitt, TL J1 - J MED MICROBIOL Y1 - 2007/05// VL - 56 SN - 0022-2615 SP - 670 EP - 674 N2 - Cystic fibrosis (CF) patients who are chronically infected with Pseudomonas aeruginosa make serum antibodies to bacterial surface LPS as well as other pseudomonas antigens. This study investigated the feasibility of using oral fluid samples for the detection of pseudomonas antibodies in CF patients and compared these results with corresponding serum antibodies. Most strains of P. aeruginosa produce two forms of LPS molecule, termed A-band (described as a common antigen) and B-band (O-serotype-specific antigen), apparently bound to a common core oligosaccharide moiety. A-band LPS was demonstrated in 45 out of 49 clinical isolates of P. aeruginosa by SDS-PAGE and immunoblotting with a specific antibody, Oral fluids were collected from 17 adult CF patients, all of whom were sputum culture positive for P. aeruginosa (13 also provided serum samples), 11 primary ciliary dyskinesia (PCD) patients and 37 healthy volunteers. Antibodies to A-band LPS were detected by immunoblotting in all of the CF patients' oral fluids but 10 of the volunteer samples gave weak reactions with immunoblotting. Six of the PCD patients gave a weak reaction with A-band antibodies and only one demonstrated antibodies to core LPS. In a quantitative ELISA, 15 of the 17 CF patients' oral fluids were shown to contain antibodies to A-band LPS, whilst none of the volunteer samples contained antibodies to A-band LPS. All serum samples from the CF patients were positive by both methods. Thus this is a sensitive procedure for the detection of antibodies to A-band LPS of P. aeruginosa in oral fluid and serum from patients with CF. ER - TY - JFULL T1 - Distal embolization after percutaneous coronary intervention in stable and unstable coronary syndromes. A1 - Locca, DA A1 - LaManna, AG A1 - Goktekin, O A1 - Tanigawa, J A1 - Keenan, N A1 - Wage, R A1 - Barlis, A A1 - Bucciarelli, C A1 - Pennell, DJ A1 - DiMario, C J1 - AM J CARDIOL Y1 - 2007/04/25/ VL - 99 SN - 0002-9149 SP - 32F EP - 32F ER - TY - JFULL T1 - Cardiac myocyte gene expression profiling during H2O2-induced apoptosis. A1 - Clerk, A A1 - Kemp, TJ A1 - Zoumpoulidou, G A1 - Sugden, PH J1 - Physiol Genomics Y1 - 2007/04/24/ VL - 29 SN - 1531-2267 SP - 118 EP - 127 N2 - High levels of oxidative stress promote cardiac myocyte death, though lower levels are potentially cytoprotective/anabolic. We examined the changes in gene expression in rat neonatal cardiac myocytes exposed to apoptotic (0.2 mM) or nontoxic (0.04 mM) concentrations of H2O2 (2, 4, or 24 h) using Affymetrix microarrays. Using U34B arrays, we identified a ubiquitously expressed, novel H2O2-responsive gene [putative peroxide-inducible transcript 1 (Perit1)], which generates two alternatively spliced transcripts. Using 230 2.0 arrays, H2O2 (0.04 mM) promoted significant changes in expression of only 32 genes, all of which were seen with 0.2 mM H2O2. We failed to detect any increase in the rate of protein synthesis in cardiac myocytes exposed to <0.1 mM H2O2, further suggesting that global, low concentrations of H2O2 are not anabolic in this system. H2O2 (0.2 mM) promoted significant (P < 0.05, >1.75-fold) changes in expression of 649 mRNAs and 187 RNAs corresponding to no established gene. Of the mRNAs, 114 encoded transcriptional regulators including Krüppel-like factors (Klfs). Quantitative PCR independently verified the changes in Klf expression. Thus, H2O2-induced cardiac myocyte apoptosis is associated with dynamic changes in gene expression. The expression of these genes and their protein products potentially influences the progression of the apoptotic response. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17148688&query_hl=1 ER - TY - JFULL T1 - Risk factors for accident and emergency attendance for asthma in inner city children. A1 - Forbes, L A1 - Harvey, S A1 - Jarvis, D A1 - Luczynska, C A1 - Newson, R A1 - Price, J A1 - Burney, P J1 - Thorax Y1 - 2007/04/24/ SN - 0040-6376 N2 - BACKGROUND: Inner city children make heavy use of accident and emergency (A and E) services for asthma. Developing strategies to reduce this requires a better understanding of the risk factors. METHODS: We carried out a case control study of children with asthma living in South East London: 1018 children who attended A and E for asthma over one year and 394 children who had not attended A and E for asthma over the previous year. The main risk factors were socioeconomic status, home environment, routine asthma management, and parents' psychological responses to, and beliefs about the treatment of asthma attacks. RESULTS: A and E attendance was more common in children living in poorer households. We found no associations with home environment nor measures of routine asthma care. Children who had attended outpatients were much more likely to attend A and E (odds ratio (OR) 13.17, 95% confidence interval (CI) 7.13, 24.33). Other risk factors included: having a parent who reported feeling alone (OR 2.58, 95% CI 1.71, 3.87) or panic or fear (OR 2.62. 95% CI 1.75, 3.93) when the child's asthma was worse; and parental belief that the child would be seen more quickly in A and E than at the GP surgery (OR 2.48, 95% CI 1.62, 3.79). Parental confidence in the GP's ability to treat asthma attacks reduced the risk of attending A and E (OR 0.30, 95% CI 0.17, 0.54). CONCLUSIONS: We found no evidence that passive smoking, damp homes or poor routine asthma care explain heavy inner city A and E use in children with asthma. Reducing A and E use is unlikely to be achieved by improving these, but identifying appropriate settings for treating children with asthma attacks and communicating these effectively may do so. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17456503&query_hl=1 ER - TY - JFULL T1 - Diagnostic criteria and adjudication process both determine published event-rates: The ACTION trial experience. A1 - Kirwan, BA A1 - Lubsen, J A1 - Brouwer, SD A1 - Danchin, N A1 - Battler, A A1 - Bayes de Luna, A A1 - Dunselman, PH A1 - Glasser, S A1 - Koudstaal, PJ A1 - Sutton, G A1 - van Dalen, FJ A1 - Poole-Wilson, PA A1 - on behalf of the ACTION (A Coronary disease Trial Investigating Outcome with Nifedipine GITS) investigators J1 - Contemp Clin Trials Y1 - 2007/04/19/ SN - 1551-7144 N2 - OBJECTIVE: Few trials report event-adjudication procedures in detail. Using data from the ACTION (A Coronary disease Trial Investigating Outcome with Nifedipine GITS) study, we compared the impact on event-rates of an adjudication strategy based on systematic screening of all reported serious adverse events (SAEs) with a strategy based on investigator diagnoses. The final diagnosis was always made by a critical events committee (CEC) using standard criteria. METHODS: ACTION randomized 7665 patients with stable angina to either nifedipine or placebo. Pre-specified events included acute or procedural myocardial infarction (MI), refractory angina, heart failure and debilitating stroke. Clinically related SAEs including in-hospital procedures were combined into episodes independent from the investigator diagnoses entered on SAE reports. All fatal episodes and those episodes suggestive of pre-specified events were adjudicated by the CEC. RESULTS: During follow-up, 17,081 episodes were reported in 5312 patients. The SAE descriptions ruled out the occurrence of a pre-specified event in 28%. The remaining 72% were adjudicated by the CEC and 616 cases of MI, 361 of refractory angina, 275 of heart failure and 190 of debilitating stroke were diagnosed (total=1442). Had adjudication by the CEC been limited to the 3924 episodes (2397 patients) that were fatal or for which the investigator had reported any of the diagnoses mentioned, 98 cases of MI, 35 of refractory angina, 81 of heart failure and 14 of debilitating stroke would have been missed (total=228). CONCLUSION: Both the diagnostic criteria used and the adjudication process determine event-rates and conclusions about treatment effects in clinical trials. Published trial reports should always state if event-adjudication was independent of the diagnoses of investigators, and if all events of interest were adjudicated or only the first one. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17509947&query_hl=1 ER - TY - JFULL T1 - Effect of inhaled furosemide on air hunger induced in healthy humans. A1 - Moosavi, SH A1 - Binks, AP A1 - Lansing, RW A1 - Topulos, GP A1 - Banzett, RB A1 - Schwartzstein, RM J1 - Respir Physiol Neurobiol Y1 - 2007/04/16/ VL - 156 SN - 1569-9048 SP - 1 EP - 8 N2 - Recent evidence suggests that inhaled furosemide relieves dyspnoea in patients and in normal subjects made dyspnoeic by external resistive loads combined with added dead-space. Furosemide sensitizes lung inflation receptors in rats, and lung inflation reduces air hunger in humans. We therefore hypothesised that inhaled furosemide acts on the air hunger component of dyspnoea. Ten subjects inhaled aerosolized furosemide (40 mg) or placebo in randomised, double blind, crossover experiments. Air hunger was induced by hypercapnia (50+/-2 mmHg) during constrained ventilation (8+/-0.9 L/min) before and after treatment, and rated by subjects using a 100 mm visual analogue scale. Subjects described a sensation of air hunger with little or no work/effort of breathing. Hypercapnia generated less air hunger in the first trial at 23+/-3 min after start of furosemide treatment (58+/-11% to 39+/-14% full scale); the effect varied substantially among subjects. The mean treatment effect, accounting for placebo, was 13% of full scale (P=0.052). We conclude that 40 mg of inhaled furosemide partially relieves air hunger within 1h and is accompanied by substantial diuresis. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16935035&query_hl=1 ER - TY - JFULL T1 - Biomarkers for cystic fibrosis - Are we progressing? A1 - Alton, EWFW A1 - Davies, JC A1 - Geddes, DM J1 - AM J RESP CRIT CARE Y1 - 2007/04/15/ VL - 175 SN - 1073-449X SP - 750 EP - 751 ER - TY - JFULL T1 - A randomized, placebo-controlled, double-blind trial of the effect of combined therapy with deferoxamine and deferiprone on myocardial iron in thalassemia major using cardiovascular magnetic resonance. A1 - Tanner, MA A1 - Galanello, R A1 - Dessi, C A1 - Smith, GC A1 - Westwood, MA A1 - Agus, A A1 - Roughton, M A1 - Assomull, R A1 - Nair, SV A1 - Walker, JM A1 - Pennell, DJ J1 - Circulation Y1 - 2007/04/10/ VL - 115 SN - 1524-4539 SP - 1876 EP - 1884 N2 - BACKGROUND: Cardiac complications secondary to iron overload are the leading cause of death in beta-thalassemia major. Approximately two thirds of patients maintained on the parenteral iron chelator deferoxamine have myocardial iron loading. The oral iron chelator deferiprone has been demonstrated to remove myocardial iron, and it has been proposed that in combination with deferoxamine it may have additional effect. METHODS AND RESULTS: Myocardial iron loading was assessed with the use of myocardial T2* cardiovascular magnetic resonance in 167 patients with thalassemia major receiving standard maintenance chelation monotherapy with subcutaneous deferoxamine. Of these patients, 65 with mild to moderate myocardial iron loading (T2* 8 to 20 ms) entered the trial with continuation of subcutaneous deferoxamine and were randomized to receive additional oral placebo (deferoxamine group) or oral deferiprone 75 mg/kg per day (combined group). The primary end point was the change in myocardial T2* over 12 months. Secondary end points of endothelial function (flow-mediated dilatation of the brachial artery) and cardiac function were also measured with cardiovascular magnetic resonance. There were significant improvements in the combined treatment group compared with the deferoxamine group in myocardial T2* (ratio of change in geometric means 1.50 versus 1.24; P=0.02), absolute left ventricular ejection fraction (2.6% versus 0.6%; P=0.05), and absolute endothelial function (8.8% versus 3.3%; P=0.02). There was also a significantly greater improvement in serum ferritin in the combined group (-976 versus -233 microg/L; P<0.001). CONCLUSIONS: In comparison to the standard chelation monotherapy of deferoxamine, combination treatment with additional deferiprone reduced myocardial iron and improved the ejection fraction and endothelial function in thalassemia major patients with mild to moderate cardiac iron loading. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17372174&query_hl=1 ER - TY - JFULL T1 - Haemodynamic significance of an anomalous right coronary with inter-arterial course assessed with intracoronary pressure measurements during dobutamine challenge. A1 - Dimopoulos, K A1 - Di Mario, C A1 - Barlis, P A1 - Pennell, D A1 - Goktekin, O A1 - Kaddoura, S A1 - Gatzoulis, MA J1 - Int J Cardiol Y1 - 2007/04/09/ SN - 1874-1754 N2 - Autopsy studies have associated congenital coronary anomalies with the risk of sudden cardiac death. However, not all patients with anomalous coronary arteries die suddenly. A means of assessing the potential for ischaemia and thus predicting the risk of sudden death in these patients may be necessary for directing treatment. We present the case of a patient with an anomalous right coronary artery originating from the aortic wall above the left sinus of Valsalva, with an anterior inter-arterial course. The haemodynamic significance of this anomaly was assessed using intracoronary pressure-wire measurements at rest and during dobutamine stress. This technique could be a valid means for assessing stress-induced ischaemia and, therefore, by inference, the risk of sudden cardiac death in these patients. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17428559&query_hl=1 ER - TY - JFULL T1 - Influence of organic diet on the amount of conjugated linoleic acids in breast milk of lactating women in the Netherlands. A1 - Rist, L A1 - Mueller, A A1 - Barthel, C A1 - Snijders, B A1 - Jansen, M A1 - Simões-Wüst, AP A1 - Huber, M A1 - Kummeling, I A1 - von Mandach, U A1 - Steinhart, H A1 - Thijs, C J1 - Br J Nutr Y1 - 2007/04// VL - 97 SN - 0007-1145 SP - 735 EP - 743 N2 - The aim of the present study was to find out whether the incorporation of organic dairy and meat products in the maternal diet affects the contents of the conjugated linoleic acid isomers (CLA) and trans-vaccenic acid (TVA) in human breast milk. To this purpose, milk samples from 312 breastfeeding mothers participating in the KOALA Birth Cohort Study have been analysed. The participants had documented varying lifestyles in relation to the use of conventional or organic products. Breast milk samples were collected 1 month postpartum and analysed for fatty acid composition. The content of rumenic acid (the main CLA) increased in a statistically significant way while going from a conventional diet (no organic dairy/meat products, 0.25 weight % (wt%), n 186) to a moderately organic diet (50-90 % organic dairy/meat, 0.29 wt%, n 33, P = 0.02) and to a strict organic diet (>90 % organic dairy/meat, 0.34 wt%, n 37, P 5 years, n = 1657) of Sobotka, a town of 4000 people in south-west Poland: and seven neighbouring villages. We measured and analysed responses to skin prick tests (atopy) and to a standard questionnaire (asthma and hayfever).Results: Atopy was very uncommon (7%) among villagers at all ages but not among townspeople (20%, P < 0.001); the differences were most marked among those aged under 40 years. Asthma and hayfever were similarly distributed, both being very rare among villagers. The differences appear to be explained by the cohort effect of a communal move away from rural life. This interpretation is supported by an ecological correlation (rho = -0.59) between rural populations and childhood wheeze in 22 European countries.Conclusion: The very striking differences in the prevalence of allergy between these two neighbouring communities of central Europe reflect the pan-continental population movements that may have been responsible for the emergence of childhood allergies in Europe. ER - TY - JFULL T1 - Autoantibodies to vimentin cause accelerated rejection of cardiac allografts. A1 - Mahesh, B A1 - Leong, HS A1 - McCormack, A A1 - Sarathchandra, P A1 - Holder, A A1 - Rose, ML J1 - Am J Pathol Y1 - 2007/04// VL - 170 SN - 0002-9440 SP - 1415 EP - 1427 N2 - Autoimmune responses to vimentin occur after solid organ transplantation, but their pathogenic effects are unclear. The aim of these studies was to investigate the effects of vimentin preimmunization on allogeneic and isografted hearts in a murine transplant model. Immunization of C57BL/6 mice with murine vimentin in complete Freund's adjuvant resulted in anti-vimentin antibodies and vimentin-reactive Th-1 cells. Transplantation of 129/sv hearts into vimentin-immunized C57BL/6 recipients resulted in accelerated rejection (8.4 +/- 1.5 days; n = 18), compared with hen egg lysozyme-immunized C57BL/6 (13.3 +/- 2.2 days; n = 10; P < 0.0001, log-rank test). In contrast, isografts continued to beat beyond 90 days. Immunohistochemical analysis of allografts from vimentin/complete Freund's adjuvant mice demonstrated increased numbers of T cells and enhanced microvascular deposition of C3d, CD41, and P-selectin compared with controls. Antibodies were necessary for accelerated rejection, shown by the fact that vimentin-immunized B-cell-deficient IgH6 mice did not show accelerated rejection of 129/sv allografts, but rejection was restored by adoptive transfer of serum containing anti-vimentin antibodies. Eluates from donor hearts placed in vimentin/complete Freund's adjuvant recipients contained anti-vimentin antibodies, shown by Western blotting. Confocal imaging of rejected hearts de-monstrated presence of vimentin and C3d on apoptosed leukocytes, endothelial cells, and platelet/leukocyte conjugates. These results demonstrate that autoantibodies to vimentin, in conjunction with the alloimmune response, have a pathogenic role in allograft rejection. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17392180&query_hl=1 ER - TY - JFULL T1 - Limitations of the New York Heart Association functional classification system and self-reported walking distances in chronic heart failure. A1 - Raphael, C A1 - Briscoe, C A1 - Davies, J A1 - Ian Whinnett, Z A1 - Manisty, C A1 - Sutton, R A1 - Mayet, J A1 - Francis, DP J1 - Heart Y1 - 2007/04// VL - 93 SN - 1468-201X SP - 476 EP - 482 N2 - BACKGROUND: Two ways to evaluate the symptoms of heart failure are the New York Heart Association (NYHA) classification and asking patients how far they can walk (walk distance). The NYHA system is commonly used, although it is not clear how individual clinicians apply it. AIM: To investigate how useful these measures are to assess heart failure and whether other questions might be more helpful. METHODS: 30 cardiologists were asked what questions they used when assessing patients with heart failure. To assess interoperator variability, two cardiologists assessed a series of 50 patients in classes II and III using the NYHA classification. 45 patients who had undergone cardiopulmonary testing were interviewed using a specially formulated questionnaire. They were also asked how far they could walk before being stopped by symptoms, and then tested on their ability to estimate distance. RESULTS: The survey of cardiologists showed no consistent method for assessing NYHA class and a literature survey showed that 99% of research papers do not reference or describe their methods for assigning NYHA classes. The interoperator variability study showed only 54% concordance between the two cardiologists. 70% of cardiologists asked patients for their walk distance; however, this walk distance correlated poorly with actual exercise capacity measured by cardiopulmonary testing (rho = 0.04, p = 0.82). CONCLUSION: No consistent method of assessing NYHA class is in use and the interoperator study on class II and class III patients gave a result little better than chance. Some potential questions are offered for use in assessment. Walking distance, although frequently asked, does not correlate with formally measured exercise capacity, even after correction for patient perception of distance, and has never been found to have prognostic relevance. Its value is therefore doubtful. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17005715&query_hl=1 ER - TY - JFULL T1 - Resolution of Inflammatory Responses: a brief introduction. A1 - Adcock, I A1 - Evans, PC J1 - Biochem Soc Trans Y1 - 2007/04// VL - 35 SN - 0300-5127 SP - 261 EP - 262 N2 - Resolution of inflammatory responses is the regulatory process that prevents prolonged inflammation, thus avoiding diseases such as atherosclerosis, rheumatoid arthritis and transplant rejection. There are various different aspects to this process which are discussed briefly here and in the accompanying papers from this Focused Meeting. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17371254&query_hl=1 ER - TY - JFULL T1 - Positional cloning of susceptibility genes for atopic dermatitis in the epidermal differentiation complex A1 - Morar, N A1 - Edster, P A1 - Street, TL A1 - Weidinger, S A1 - Di, W A1 - Dixon, AL A1 - Taylor, M A1 - Holt, R A1 - Broxholme, J A1 - Kloop, N A1 - Novak, N A1 - Bockelbrinck, A A1 - Ragoussis, J A1 - Illig, T A1 - Harper, JI A1 - Cookson, WO A1 - Moffatt, MF J1 - J INVEST DERMATOL Y1 - 2007/04// VL - 127 SN - 0022-202X SP - S89 EP - S89 ER - TY - JFULL T1 - Early detection of cystic fibrosis lung disease: multiple-breath washout versus raised volume tests A1 - Lum, S A1 - Gustafsson, P A1 - Ljungberg, H A1 - Hulskamp, G A1 - Bush, A A1 - Carr, SB A1 - Castle, R A1 - Hoo, AF A1 - Price, J A1 - Ranganathan, S A1 - Stroobant, J A1 - Wade, A A1 - Wallis, C A1 - Wyatt, H A1 - Stocks, J A1 - London Cystis Fibrosis Collaborati J1 - THORAX Y1 - 2007/04// VL - 62 SN - 0040-6376 SP - 341 EP - 347 N2 - Background: Lung clearance index (LCI), a measure of ventilation inhomogeneity derived from the multiple-breath inert gas washout (MBW) technique, has been shown to detect abnormal lung function more readily than spirometry in preschool children with cystic fibrosis, but whether this holds true during infancy is unknown.Objectives: To compare the extent to which parameters derived from the MBW and the raised lung volume rapid thoraco-abdominal compression (RVRTC) techniques identify diminished airway function in infants with cystic fibrosis when compared with healthy controls.Methods: Measurements were performed during quiet sleep, with the tidal breathing MBW technique being performed before the forced expiratory manoeuvres.Results: Measurements were obtained in 39 infants with cystic fibrosis (mean (SD) age 41.4 (22.0) weeks) and 21 controls (37.0 (15.1) weeks). Infants with cystic fibrosis had a significantly higher respiratory rate (38 (10) vs 32 (5) bpm) and LCI (8.4 (1.5) vs 7.2 (0.3)), and significantly lower values for all forced expiratory flow-volume parameters compared with controls. Girls with cystic fibrosis had significantly lower forced expiratory volume (FEV0.5 and FEF25-75) than boys (mean (95% CI girls-boys): -1.2 (-2.1 to -0.3) for FEV0.5 Z score; FEF25-75: -1.2 (-2.2 to -0.15)). When using both the MBW and RVRTC techniques, abnormalities were detected in 72% of the infants with cystic fibrosis, with abnormalities detected in 41% using both techniques and a further 15% by each of the two tests performed.Conclusions: These findings support the view that inflammatory and/or structural changes in the airways of children with cystic fibrosis start early in life, and have important implications regarding early detection and interventions. Monitoring of early lung disease and functional status in infants and young children with cystic fibrosis may be enhanced by using both MBW and the RVRTC. ER - TY - JFULL T1 - Interruption of the aorta with multilobulated arch aneurysms: a new clinicopathologic entity. A1 - Tsang, VT A1 - Kilner, PJ A1 - Hsia, TY A1 - Hughes, S A1 - Yacoub, M J1 - J Thorac Cardiovasc Surg Y1 - 2007/04// VL - 133 SN - 1097-685X SP - 1092 EP - 1093 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17382661&query_hl=1 ER - TY - JFULL T1 - Airway glucose concentrations and effect on growth of respiratory pathogens in cystic fibrosis. A1 - Brennan, AL A1 - Gyi, KM A1 - Wood, DM A1 - Johnson, J A1 - Holliman, R A1 - Baines, DL A1 - Philips, BJ A1 - Geddes, DM A1 - Hodson, ME A1 - Baker, EH J1 - J Cyst Fibros Y1 - 2007/04// VL - 6 SN - 1569-1993 SP - 101 EP - 109 N2 - BACKGROUND: Pulmonary decline accelerates in cystic fibrosis-related diabetes (CFRD) proportional to severity of glucose intolerance, but mechanisms are unclear. In people without CF, airway glucose (AG) concentrations are elevated when blood glucose (BG)> or =8 mmol L(-1) (airway threshold), and are associated with acquisition of respiratory infection. METHODS: To determine the relationship between BG and AG, 40 CF patients underwent paired BG and AG (nasal) measurements. Daily time with BG>airway threshold was compared in 10 CFRD, 10 CF patients with normal glucose tolerance (CF-NGT) and 10 healthy volunteers by continuous BG monitoring. The effect of glucose at airway concentrations on bacterial growth was determined in vitro by optical densitometry. RESULTS: AG was present more frequently (85%-vs.-19%, p<0.0001) and at higher concentrations (0.5-3 mmol L(-1)-vs.-0.5-1 mmol L(-1), p<0.0001) when BG was > or =8 mmol L(-1)-vs.-<8 mmol L(-1). Daily time with BG> or =8 mmol L(-1) was CFRD (49+/-25%), CF-NGT (6+/-5%), healthy volunteers (1+/-3%), p<0.0001. Staphylococcus aureus growth increased at > or =0.5 mmol L(-1) (p=0.006) and Pseudomonas aeruginosa growth above 1-4 mmol L(-1) glucose (p=0.039). CONCLUSIONS: BG> or =8 mmol L(-1) predicted elevated AG concentrations in CF, at least in nasal secretions. CFRD patients spent approximately 50% day with BG>airway threshold, implying persistently elevated AG concentrations. Further studies are required to determine whether elevated airway glucose concentrations contribute to accelerated pulmonary decline in CFRD. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16844431&query_hl=1 ER - TY - JFULL T1 - Haplotype of growth hormone and angiotensin I-converting enzyme genes, serum angiotensin I-converting enzyme and ventricular growth: pathway inference in pharmacogenetics A1 - Huang, SW A1 - Chen, XH A1 - Payne, JR A1 - Pennell, DJ A1 - Gohlke, P A1 - Smith, MJ A1 - Day, INM A1 - Montgomery, HE A1 - Gaunt, TR J1 - PHARMACOGENET GENOM Y1 - 2007/04// VL - 17 SN - 1744-6872 SP - 291 EP - 294 N2 - Objectives An insertion/deletion (I/D) polymorphism in the angiotensin I-converting enzyme (ACE) gene is associated with variations in circulating and tissue angiotensin I-converting enzyme activity, and differences in exercise-induced left ventricular hypertrophic response. A genetic marker (CSH1.01) in the syntenic GH-CSH gene cluster correlates with metabolic syndrome in adult life in males. Approximately 24% linkage disequilibrium between CSH1.01T and D alleles of ACE I/D has also been reported. The objective was to examine the hypothesis that effects ascribed to ACE genotype may reflect causality in the GH-CSH cluster.Methods The ACE I/D polymorphism and GH-CSH BgIII-B single nucleotide polymorphism (in strong linkage disequilibrium with CSH1.01) were determined in 847 British Army recruits. Serum angiotensin I-converting enzyme activity and left ventricular mass were measured before and after a 12-week physical training program. Genotype and haplotype analyses of both markers were performed in relation to these phenotypes.Results The ACE I/D polymorphism was in linkage disequilibrium with BgIII-B (D'=0.3). Strong association was seen between ACE I/D genotypes and serum angiotensin I-converting enzyme activity (P < 0.0001), but not left ventricular mass change. BgIII-B genotypes also associated significantly with serum angiotensin I-converting enzyme level (P < 0.0001). Haplotype analysis, however, showed that most of this association resulted from linkage disequilibrium between BgIII-B and ACE I/D. BgIII-B did not associate with left ventricular mass change.Conclusions GH-CSH BgIII-B genotype associates significantly with angiotensin I-converting enzyme levels, but only through linkage disequilibrium with ACE I/D. Every phenotype with which ACE I/D has been associated merits investigation of potential causal effects originating in the GH-CSH cluster (and vice versa), otherwise the chain of causality could be misinterpreted. ER - TY - JFULL T1 - Allergic rhinitis and its impact on asthma update: Allergen immunotherapy A1 - Passalacqua, G A1 - Durham, SR A1 - Global Allergy Asthma J1 - J ALLERGY CLIN IMMUN Y1 - 2007/04// VL - 119 SN - 0091-6749 SP - 881 EP - 891 N2 - The Allergic Rhinitis and its Impact on Asthma document was first published in 2001. Since then, new data on specific immunotherapy have appeared. This review is intended as an update to the original document. MedLine (2001 to June 2006) was searched with appropriate key words, and panelists were asked to identify further relevant articles. Randomized controlled trials were considered for the evaluation of efficacy. For the evaluation of safety, and additional effects, studies with lower grades of evidence were included. The clinical efficacy of injection immunotherapy in rhinitis and asthma was confirmed, as well as the safety, provided that recommendations are followed. Studies have demonstrated the long-term efficacy and the preventive effect of immunotherapy in reducing the onset of new sensitizations. One randomized open trial demonstrated that in children with allergic rhinitis, injection immunotherapy may reduce the risk of developing asthma. There is strong evidence that sublingual immunotherapy is effective in allergic rhinitis in adults. Recent meta-analyses demonstrated its efficacy in allergic rhinitis in children and in asthma, although more definitive trials are required. Current data indicate that sublingual immunotherapy is safe and the rate of adverse reactions is not greater below 5 years of age. One randomized open trial showed that in children with allergic rhinitis, sublingual immunotherapy reduced the onset of asthma. Further studies are needed to identify the optimal maintenance dose and to elucidate the mechanism of action. Novel approaches for immunotherapy are currently under evaluation, including the use of adjuvants, peptides. and DNA-conjugated and recombinant allergens. ER - TY - JFULL T1 - Early allergen exposure and atopic eczema. A1 - Harris, JM A1 - Williams, HC A1 - White, C A1 - Moffat, S A1 - Mills, P A1 - Newman Taylor, AJ A1 - Cullinan, P J1 - Br J Dermatol Y1 - 2007/04// VL - 156 SN - 0007-0963 SP - 698 EP - 704 N2 - BACKGROUND: The relationship between exposure to indoor aeroallergens in early life and subsequent eczema is unclear. We have previously failed to show any significant associations between early life exposure to house dust mite and cat fur allergens and either sensitization to these allergens or wheeze. We have also previously reported a lower prevalence of parent-reported, doctor-diagnosed eczema by age 2 years for children exposed to higher concentrations of house dust mite, but no other associations with other definitions of eczema or for exposure to cat allergen. OBJECTIVES: To extend the exposure-response analysis of allergen exposure and eczema outcomes measured up to age 8 years, and to investigate the role of other genetic and environmental determinants. METHODS: A total of 593 children (92 x 4% of those eligible) born to all newly pregnant women attending one of three general practitioner surgeries in Ashford, Kent, were followed from birth to age 8 years. Concentrations of house dust mite and cat allergen were measured in dust samples collected from the home at 8 weeks after birth. The risk of subsequent eczema as defined by the U.K. diagnostic criteria was determined according to different levels (quintiles) of allergen exposure at birth. RESULTS: By age 8 years, 150 (25 x 3%) children had met the diagnostic criteria for eczema at least once. Visible flexural dermatitis was recorded at least once for 129 (28 x 0%). As in other studies, parental allergic history was positively associated with most eczema outcomes, as were higher maternal education and less crowded homes. No clear linear associations between early exposure to house dust mite or cat allergen were found, regardless of the definition of eczema used. The risk of eczema appeared to increase for the three lowest quintiles of house dust mite allergen exposure (odds ratio, OR 1 x 37 for third quintile compared with first), and then to fall for the two highest quintiles (OR 0 x 66 and 0 x 71) even after controlling for confounding factors. CONCLUSIONS: The lack of any clear exposure-disease relationship between allergens in early life and subsequent eczema argues against allergen exposure being a major factor causing eczema. If the lower levels of eczema at higher levels of house dust mite are confirmed, then interventions aimed at reducing house dust mite in early infancy could paradoxically increase the risk of subsequent eczema. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17263823&query_hl=1 ER - TY - JFULL T1 - Impact of post-translational modifications of proteins on the inflammatory process. A1 - Ito, K J1 - Biochem Soc Trans Y1 - 2007/04// VL - 35 SN - 0300-5127 SP - 281 EP - 283 N2 - PTM (post-translational modification) is the chemical modification of a protein after its translation. The well-studied PTM is phosphorylation, but, recently, PTMs have been re-focused by extensive studies on histone modifications and the discovery of the ubiquitin system. Histone acetylation is the well-established epigenetic regulator for gene expression. Recent studies show that different patterns of PTMs and cross-talk of individual modifications (acetylation, methylation, phosphorylation) are keys of gene regulation (known as the 'histone code'). As well as histone, non-histone proteins are also targets of acetylation. For instance, NF-kappaB (nuclear factor kappaB), a transcriptional factor, is regulated dynamically by acetylation/deacetylation. Acetylation of NF-kappaB [RelA (p65)] at Lys(310) enhances its transcriptional activity, which is inhibited by SIRT1 deacetylase, type III HDAC (histone deacetylase). We also found that acetylated NF-kappaB preferentially bound to the IL-8 (interleukin 8) gene promoter, but not to GM-CSF (granulocyte/macrophage colony-stimulating factor), suggesting NF-kappaB acetylation is involved in selective gene induction as well as an increased level of transcription. A receptor of glucocorticoid, a potent anti-inflammatory agent, is also a target of acetylation. The glucocorticoid receptor is highly acetylated after ligand binding but its deacetylation is necessary for gene repression through binding to NF-kappaB. As well as acetylation, other PTMs, such as nitration, carbonylation and ubiquitination on transcriptional/nuclear factors, are taking part in the inflammatory process. Cross-talk of individual modifications on proteins deserves further evaluation in the future (as 'protein code'). L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17371260&query_hl=1 ER - TY - JFULL T1 - A randomized trial of carvedilol after renin-angiotensin system inhibition in chronic Chagas cardiomyopathy. A1 - Botoni, FA A1 - Poole-Wilson, PA A1 - Ribeiro, AL A1 - Okonko, DO A1 - Oliveira, BM A1 - Pinto, AS A1 - Teixeira, MM A1 - Teixeira, AL A1 - Reis, AM A1 - Dantas, JB A1 - Ferreira, CS A1 - Tavares, WC A1 - Rocha, MO J1 - Am Heart J Y1 - 2007/04// VL - 153 SN - 1097-6744 SP - 544.e1 EP - 548.e1 N2 - OBJECTIVE: The objective of this study was to determine the safety and efficacy of renin-angiotensin system (RAS) inhibitors and beta-blockers in chronic Chagas cardiomyopathy. BACKGROUND: Chronic Chagas cardiomyopathy causes substantial morbidity and mortality in Latin America. Whether RAS inhibitors and beta-blockers are safe and beneficial has been challenged because of the lack of formal trials. METHODS: We conducted a double-blind, placebo-controlled, and randomized trial in 42 patients with Trypanosoma cruzi infection and cardiomyopathy. All patients received enalapril (up-titrated to 20 mg BID) and spironolactone (25 mg QD). Subsequently, the patients were randomly assigned to receive placebo (n = 20) or carvedilol up-titrated to 25 mg BID (n = 19). The primary end points were change in left ventricular ejection fraction (LVEF) after RAS inhibition and that after the addition of carvedilol. The secondary end points were changes in other echocardiographic parameters, Framingham score, quality of life (36-item Short-Form Health Survey), New York Heart Association class, radiographic indices, brain natriuretic peptide levels, and chemokines as well as safety end points. RESULTS: Optimization of RAS inhibition was safe, hemodynamically well tolerated, and associated with improvements in Framingham score (P = .001) and quality of life as well as reductions in the cardiothoracic index (P = .002), brain natriuretic peptide level (P = .032), and RANTES (regulated on activation, normal T expressed and secreted) level (P = .001). Left ventricular ejection fraction increased by 2.3% (P = .25); in patients with an LVEF < or = 45% at baseline, it increased by 2.8% (P = .017). Treatment with carvedilol was associated with a trend toward an increase in LVEF (absolute difference between groups, 2.3%; P = .094). The addition of carvedilol was safe, hemodynamically well tolerated, and not associated with symptomatic bradycardia. CONCLUSIONS: In patients with chronic Chagas cardiomyopathy, optimization of treatment with enalapril and spironolactone and subsequent addition of carvedilol were safe and associated with benefits in cardiac function and clinical status. Larger trials are needed to show effects on mortality and/or hospitalization. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17383291&query_hl=1 ER - TY - JFULL T1 - Effect of spironolactone on blood pressure in subjects with resistant hypertension. A1 - Chapman, N A1 - Dobson, J A1 - Wilson, S A1 - Dahlöf, B A1 - Sever, PS A1 - Wedel, H A1 - Poulter, NR A1 - Anglo-Scandinavian Cardiac Outcomes Trial Investigators J1 - Hypertension Y1 - 2007/04// VL - 49 SN - 1524-4563 SP - 839 EP - 845 N2 - Spironolactone is recommended as fourth-line therapy for essential hypertension despite few supporting data for this indication. We evaluated the effect among 1411 participants in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm who received spironolactone mainly as a fourth-line antihypertensive agent for uncontrolled blood pressure and who had valid BP measurements before and during spironolactone treatment. Among those who received spironolactone, the mean age was 63 years (SD: +/-8 years), 77% were men, and 40% had diabetes. Spironolactone was initiated a median of 3.2 years (interquartile range: 2.0 to 4.4 years) after randomization and added to a mean of 2.9 (SD: +/-0.9) other antihypertensive drugs. The median duration of spironolactone treatment was 1.3 years (interquartile range: 0.6 to 2.6 years). The median dose of spironolactone was 25 mg (interquartile range: 25 to 50 mg) at both the start and end of the observation period. During spironolactone therapy, mean blood pressure fell from 156.9/85.3 mm Hg (SD: +/-18.0/11.5 mm Hg) by 21.9/9.5 mm Hg (95% CI: 20.8 to 23.0/9.0 to 10.1 mm Hg; P<0.001); the BP reduction was largely unaffected by age, sex, smoking, and diabetic status. Spironolactone was generally well tolerated; 6% of participants discontinued the drug because of adverse effects. The most frequent adverse events were gynecomastia or breast discomfort and biochemical abnormalities (principally hyperkaliemia), which were recorded as adverse events in 6% and 2% of participants, respectively. In conclusion, spironolactone effectively lowers blood pressure in patients with hypertension uncontrolled by a mean of approximately 3 other drugs. Although nonrandomized and not placebo controlled, these data support the use of spironolactone in uncontrolled hypertension. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17309946&query_hl=1 ER - TY - JFULL T1 - Expression and activation of TGF-beta isoforms in acute allergen-induced remodelling in asthma. A1 - Torrego, A A1 - Hew, M A1 - Oates, T A1 - Sukkar, M A1 - Fan Chung, K J1 - Thorax Y1 - 2007/04// VL - 62 SN - 0040-6376 SP - 307 EP - 313 N2 - BACKGROUND: Airway wall remodelling and inflammation are features of chronic asthma. Transforming growth factor beta (TGF-beta) has been implicated in these processes. AIM: To determine the effect of allergen challenge on airway inflammation and remodelling and whether TGF-beta isoforms and the Smad signalling pathways are involved. METHODS: Thirteen patients with atopic asthma underwent inhalational challenge with 0.9% saline, followed by allergen 3-4 weeks later. After both challenges, fibreoptic bronchoscopy was undertaken to obtain bronchial biopsies and tissue samples were processed for immunohistochemistry and examined by microscopy. RESULTS: Forced expiratory volume in 1 s (FEV(1)) fell after allergen challenge (mean (SE) -28.1 (0.9)% at 30 min with a late response at 7 hours (-23.0 (1.2)%). Allergen challenge caused an increase in neutrophils and eosinophils in the bronchial mucosa compared with saline. Sub-basement membrane (SBM) thickness did not change after allergen, but tenascin deposition in SBM was increased. Intranuclear (activated) Smad 2/3 and Smad 4 detected by immunohistochemistry were increased after allergen challenge in epithelial and subepithelial cells of bronchial biopsies. No inhibitory Smad (Smad 7) protein was detected. TGF-beta isoforms 1, 2 and 3 were expressed predominantly in bronchial epithelium after saline and allergen challenges, but only TGF-beta(2) expression was increased after allergen. Double immunostaining showed an increase in TGF-beta(2) positive eosinophils and neutrophils but not in TGF-beta(1) positive eosinophils and neutrophils after allergen challenge. CONCLUSIONS: TGF-beta(2) may contribute to the remodelling changes in allergic asthma following single allergen exposure. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17251317&query_hl=1 ER - TY - JFULL T1 - Role of non-invasive imaging in the management of coronary artery disease: an assessment of likely change over the next 10 years. A report from the British Cardiovascular Society Working Group A1 - Gershlick, AH A1 - de Belder, M A1 - Chambers, J A1 - Hackett, D A1 - Keal, R A1 - Kelion, A A1 - Neubauer, S A1 - Pennell, DJ A1 - Rothman, M A1 - Signy, M A1 - Wilde, P J1 - HEART Y1 - 2007/04// VL - 93 SN - 1355-6037 SP - 423 EP - 431 N2 - Coronary angiography has been the gold standard for determining the severity, extent and prognosis of coronary atheromatous disease for the past 15-20 years. However, established non-invasive testing (such as myocardial perfusion scintigraphy and stress echocardiography) and newer imaging modalities (multi-detector x ray computed tomography and cardiovascular magnetic resonance) now need to be considered increasingly as a challenge to coronary angiography in contemporary practice. An important consideration is the degree to which appropriate use of such techniques impacts on the need for coronary angiography over the next 10-15 years. This review aims to determine the role of the various investigation techniques in the management of coronary artery disease and their resource implications, and should help determine future service provision, accepting that we are in a period of significant technological change. ER - TY - JFULL T1 - Hydrogen peroxide in exhaled breath condensate (EBC) vs eosinophil count in induced sputum (IS) in parenchymal vs airways lung diseases. A1 - Fireman, E A1 - Shtark, M A1 - Priel, IE A1 - Shiner, R A1 - Mor, R A1 - Kivity, S A1 - Fireman, Z J1 - Inflammation Y1 - 2007/04// VL - 30 SN - 0360-3997 SP - 44 EP - 51 N2 - We compared exhaled breath condensate (EBC) and induced sputum (IS) for assessing inflammation in pulmonary diseases in patients with obstructive lung disease (n = 20), persistent cough >6 months (n = 20), interstitial lung disease (n = 25) and controls (n = 10). EBC was collected by suspending a Teflon perfluoroalkoxy tube installed in an ice-filled container and connected to a polypropylene test tube. IS was recovered after 20' inhalation of 3% saline with an ultrasonic nebulizer, and 300 cells were differentially counted in cytospin Giemsa-stained slides. H(2)0(2) was measured by a method based on oxidation of phenolsulfonphthalein (phenol red) mediated by horseradish peroxidases and H(2)0(2). Pulmonary function tests were performed by conventional methods. H(2)0(2) levels in EBC and % eosinophils in IS were significantly different between groups. A positive and significant correlation was found between % eosinophils in IS and the levels of H(2)0(2) in EBC for each group and for all patients combined. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17372840&query_hl=1 ER - TY - JFULL T1 - Endothelium-dependent dilatation of mice pulmonary arteries increases with postnatal maturation A1 - Moreno, L A1 - Faro, R A1 - Hislop, A A1 - Sturton, G A1 - Perez-Vizcaino, F A1 - Mitchell, JA J1 - FASEB J Y1 - 2007/04// VL - 21 SN - 0892-6638 SP - A1164 EP - A1164 ER - TY - JFULL T1 - Eczema, atopy and allergen exposure in adults: a population-based study. A1 - Harrop, J A1 - Chinn, S A1 - Verlato, G A1 - Olivieri, M A1 - Norbäck, D A1 - Wjst, M A1 - Janson, C A1 - Zock, JP A1 - Leynaert, B A1 - Gislason, D A1 - Ponzio, M A1 - Villani, S A1 - Carosso, A A1 - Svanes, C A1 - Heinrich, J A1 - Jarvis, D J1 - Clin Exp Allergy Y1 - 2007/04// VL - 37 SN - 0954-7894 SP - 526 EP - 535 N2 - BACKGROUND: There are few published studies on geographical variation in prevalence of eczema in adults or its association with recognised risk factors for allergic disease. OBJECTIVE: To describe the geographical variation in prevalence of eczema in adults, assess the associations with sociodemographic risk factors, serum-specific IgE and IgG, and exposure to allergen. METHODS: A community-based sample of 8206 adults aged 27-56 years, in 25 European centres and Portland, USA, provided questionnaire information on symptoms of eczema. Serum-specific IgE to house dust mite (HDM), cat, grass and Cladosporium, and IgG and IgG4 to HDM and cat were measured. Mattress levels of mite and cat allergen were assessed. RESULTS: Overall prevalence of eczema was 7.1% (range between countries of 2.2-17.6%). Eczema was associated with female gender [odds ratio (OR) 1.25; 95% confidence interval (CI) (1.01-1.55)], family history of atopic disease (OR 1.43; 95% CI 1.18-1.74), IgE sensitization to at least one allergen (OR 1.50; 95% CI 1.19-1.90), particularly Cladosporium (OR 3.65; 95% CI 1.81-7.37), and total IgE. Eczema was negatively associated with age and no clear associations were observed with sibship size, mattress mite and cat allergen levels or with cat and HDM-specific IgG or IgG4. CONCLUSIONS: There is geographical variation in the prevalence of eczema in adults both within and between countries. Although the disease is associated with IgE sensitization, in this study it was not related to mattress mite or cat allergen levels. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17430349&query_hl=1 ER - TY - JFULL T1 - HDAC inhibitors as anti-inflammatory agents. A1 - Adcock, IM J1 - Br J Pharmacol Y1 - 2007/04// VL - 150 SN - 0007-1188 SP - 829 EP - 831 N2 - Diverse cellular functions including the regulation of inflammatory gene expression, DNA repair and cell proliferation are regulated by changes in the acetylation status of histones and non-histone proteins. Many human diseases, particularly cancer, have been associated with altered patterns of histone acetylation. Furthermore, abnormal expression and activation of histone acetyltransferases, which act as transcriptional co-activators, has been reported in inflammatory diseases. Histone deacetylase (HDAC) inhibitors have been developed clinically for malignancies due to their effects on apoptosis. More recently, in vitro and in vivo data indicates that HDAC inhibitors may be anti-inflammatory due to their effects on cell death acting through acetylation of non-histone proteins. Although there are concerns over the long-term safety of these agents, they may prove useful particularly in situations where current anti-inflammatory therapies are suboptimal. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17325655&query_hl=1 ER - TY - JFULL T1 - Normal bronchial blood flow in COPD is unaffected by inhaled corticosteroids and correlates with exhaled nitric oxide. A1 - Paredi, P A1 - Ward, S A1 - Cramer, D A1 - Barnes, PJ A1 - Kharitonov, SA J1 - Chest Y1 - 2007/04// VL - 131 SN - 0012-3692 SP - 1075 EP - 1081 N2 - BACKGROUND: In COPD patients, there is reduced vascularity and inflammation of the bronchi, which may have opposite effects on bronchial blood flow (QAW). We studied the relationship of QAW with the fraction of exhaled nitric oxide (FENO), which is a potent vasodilator. We also investigated the vascular response to budesonide and a beta(2)-agonist. METHODS: We measured QAW in 17 patients with COPD (mean [+/- SEM] age, 67 +/- 3 years; 10 male patients; mean FEV(1), 57 +/- 3% predicted; mean FEV(1)/FVC ratio, 54 +/- 4%), all of whom were ex-smokers, and in 16 age-matched nonsmoking volunteers (mean age, 64 +/- 4 years) and compared this to FENO. QAW was measured using the acetylene dilution method. RESULTS: Mean QAW was similar in patients with COPD (34.29 +/- 1.09 microL/mL/min) compared to healthy subjects (35.50 +/- 1.74 microL/mL/min; p > 0.05) and was not affected by long-term treatment (35.89 +/- 1.63 microL/mL/min) or short-term treatment (32.50 +/- 1.24 microL/mL/min; p < 0.05) with inhaled budesonide. QAW positively correlated with the diffusion of carbon monoxide (ie, carbon monoxide transfer coefficient: r = 0.74; p < 0.05). FENO levels were mildly elevated in steroid-treated patients (10.89 +/- 0.87 parts per billion [ppb]) and untreated patients (9.40 +/- 0.86 ppb) compared to the control group (8.22 +/- 0.57 ppb; p < 0.05) and were correlated with QAW (r = 0.6; p < 0.05). Ten minutes after the inhalation of 200 microg of albuterol, QAW was more elevated in healthy control subjects (59.33 +/- 2.40 microL/mL/min) compared to COPD patients (38.00 +/- 0.58 microL/mL/min; p < 0.05), indicating that COPD patients may have a reduced bronchial vascular reactivity. CONCLUSIONS: QAW is normal in COPD patients and is not affected by therapy with inhaled corticosteroids or beta(2)-agonists. In addition, QAW correlates with levels of FENO, which may have a regulatory role. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17426212&query_hl=1 ER - TY - JFULL T1 - Therapeutic potential of phosphatidylinositol 3-kinase inhibitors in inflammatory respiratory disease. A1 - Ito, K A1 - Caramori, G A1 - Adcock, IM J1 - J Pharmacol Exp Ther Y1 - 2007/04// VL - 321 SN - 0022-3565 SP - 1 EP - 8 N2 - The phosphoinositide 3-kinase(s) (PI3K) are a family of proteins that catalyze the phosphorylation of the 3-OH position of phosphoinositides and generate lipids that control a wide variety of intracellular signaling pathways. They are classified into three families according to their structure and substrate specificity and are thought to have distinct biological roles. Recent studies suggested that numerous components of the PI3K pathway play a crucial role in the expression and activation of inflammatory mediators, inflammatory cell recruitment, immune cell function, airway remodeling, and corticosteroid insensitivity in chronic inflammatory respiratory disease. Selective PI3K inhibitors have been developed that reduce inflammation and some characteristics of disease in experimental animal models. Targeting specific PI3K isoforms that may be overexpressed or overactive in disease should allow for selective treatment of respiratory diseases. Encouraging data from animal models, primary cells and clinical studies in other diseases suggest that inhibitors of PI3K/Akt may prove to be useful novel therapies in the treatment of asthma and chronic obstructive pulmonary disease. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17021257&query_hl=1 ER - TY - JFULL T1 - Tradition and innovation: finding the right balance. A1 - Durham, SR J1 - J Allergy Clin Immunol Y1 - 2007/04// VL - 119 SN - 0091-6749 SP - 792 EP - 795 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17418659&query_hl=1 ER - TY - JFULL T1 - Grass pollen immunotherapy induces an allergen-specific IgA2 antibody response associated with mucosal TGF-beta expression. A1 - Pilette, C A1 - Nouri-Aria, KT A1 - Jacobson, MR A1 - Wilcoc