TY - BOOK T1 - PCR Technology: Current Innovations A1 - Various ED - T. Weissensteiner, H. G. Griffin, A. M. Griffin Y1 - 2003/11/13/ VL - 2 IS - 1 PB - Taylor and Franceis CY - Baton Rouge SN - 0849311845 SP - 1 EP - 416 N2 - - UR - http://www.crcpress.co.uk/shopping_cart/products/product_reviews.asp?id=&parent_id=&sku=1184&pc= L1 - http://www.biosciencenetbase.com/ejournals/books/book_summary/features.asp?id=4747 ER - TY - BOOK T1 - Mosby's Colour Atlas and Text of Gastroenterology and Liver Disease A1 - Aspinall RJ A1 - Taylor-Robinson SD Y1 - 2002/// SN - 0-7234-3103-5 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 - 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 - Medical Image Registration A1 - Hajnal JV ED - Hajnal JV; Hawkes DJ; Hill DG Y1 - 2001/// PB - CRC Press CY - Baton Rouge, Florida. SN - 0-8493-0064-9 N2 - - ER - TY - BOOK T1 - Diagnostic and Therapeutic Antibodies A1 - George AJT A1 - Urch CE Y1 - 2000/// PB - Humana Press CY - Totowa, New Jersey SN - 0-89603-798-3 SP - 1 EP - 477 N2 - - ER - TY - CHAP T1 - Optimization of MRI Contrast for Pre-Clinical Studies at High Magnetic Field A1 - Kuo, Y-T A1 - Herlihy, A H ED - Graham A. Webb T2 - Modern Magnetic Resonance Y1 - 2006/// M2 - 1 PB - Springer SP - 753 EP - 762 N2 - - ER - TY - CHAP T1 - Transplantation and Rejection A1 - Lechler, RI A1 - George, AJT ED - Male D., Brostoff J., Roth D.B. and Roitt I. T2 - Immunology Y1 - 2006/// VL - 7th PB - Mosby Elsevier CY - Philadelphia SN - 0-323-03399-7 SP - 383 EP - 399 N2 - - ER - TY - CHAP T1 - Technology in Surgical Education A1 - Kneebone R A1 - Bello F ED - Taylor I T2 - Recent Advances in Surgery Y1 - 2005/04// M2 - 28 PB - Royal Society of Medicine Press Ltd CY - London SN - 1-85315-610-8 SP - 9 EP - 21 N2 - - UR - http://www.rsmpress.co.uk/bkirving2.htm ER - TY - CHAP T1 - The internal capsule in neonatal imaging. A1 - Cowan FM A1 - de Vries LS T2 - Seminars in Fetal and Neonatal Medicine Y1 - 2005/// M2 - 10 SP - 461 EP - 474 N2 - - ER - TY - CHAP T1 - Nuclear Magnetic Resonance Spectroscopy in the Study of Human Liver A1 - Lim AKP A1 - Khan SA A1 - Cox IJ A1 - Taylor-Robinson SD ED - Tosi, R., Tugnoli, V. T2 - Nuclear Magnetic Resonance Spectroscopy in the Study of Neoplastic Tissue Y1 - 2005/// PB - Nova Science Publishers Inc. CY - New York SN - 1-59454-258-9 SP - 295 EP - 312 N2 - - ER - TY - CHAP T1 - Monoclonal antibody therapy A1 - George AJT ED - Kaufmann SHE; Steward MW T2 - Topley & Wilson's Microbiology and Microbial Infections: Immunology. 10th Edition Y1 - 2005/// PB - Hodder Arnold CY - London SN - 0 340 88569 6 SP - 353 EP - 374 N2 - - ER - TY - CHAP T1 - Principles and practice of image-guided neurosurgery A1 - Aquilina K A1 - Edwards PJ A1 - Strong AJ ED - Anne J Moore, David W. Newell T2 - Springer Specialist Surgical Series: Neurosurgery Y1 - 2005/// SN - 1-85233-522-X N2 - - ER - TY - CHAP T1 - Defining outcome in newborns with neurological problems – a state of the art review. A1 - Graça A A1 - Cowan F T2 - Portuguese Paediatric Journal Y1 - 2005/// N2 - - ER - TY - CHAP T1 - Central nervous system complications A1 - Forton DM A1 - Taylor-Robinson SD A1 - Cox IJ A1 - Thomas HC ED - Thomas HC, Lemon S, Zuckerman A. T2 - Viral Hepatitis Y1 - 2005/// VL - 3rd M2 - 29 PB - Blackwell Publishing Ltd CY - Oxford SN - 1-4051-3005-9 SP - 482 EP - 495 N2 - - ER - TY - CHAP T1 - Magnetic resonance imaging of injury to the preterm brain. A1 - Dyet LE A1 - Cowan F T2 - Recent advances in Paediatrics Y1 - 2005/// M2 - 22 SP - 85 EP - 104 N2 - - ER - TY - CHAP T1 - Apoptosis and Necrosis A1 - Mehmet H A1 - BeesleyJ A1 - Edwards AD ED - Polin R, Fox W, Abman S. T2 - Fetal and neonatal physiology Y1 - 2004/// PB - Saunders CY - Philadelphia SP - 72 EP - 87 N2 - - ER - TY - CHAP T1 - The application of magnetic resonance imaging and spectroscopy to gene therapy. A1 - Bhakoo KK A1 - Bell JD A1 - Cox IJ A1 - Taylor-Robinson SD ED - Conn MP T2 - Methods Enzymol. Y1 - 2004/// PB - Elsevier Academic Press SN - 0-12-182791-7 SP - 13 EP - 303 N2 - - ER - TY - CHAP T1 - The value of the autopsy in determining the cause of failure to respond to resuscitation at birth. A1 - Cowan F A1 - Squier W T2 - Seminars in Neonatology Y1 - 2004/// M2 - 9 SP - 331 EP - 345 N2 - - ER - TY - CHAP T1 - Recent trends in the care complications and outcome of prematurity A1 - Azzopardi D A1 - Mallaiah R ED - Hilary Critchley, Phillip Bennett, Steven Thornton T2 - Preterm Birth Y1 - 2004/// PB - RCOG SN - 1-9003-6492-1 N2 - - ER - TY - CHAP T1 - Optimizing PCR with the Aid of Experimental Design A1 - Weissensteiner, T ED - T. Weissensteiner, H. G. Griffin, A. M. Griffin T2 - PCR Technology: Current Innovations Y1 - 2003/11/13/ VL - 2 M2 - 1 PB - Taylor and Francis CY - Baton Rouge SN - 0849311845 SP - 1 EP - 416 N2 - - UR - http://www.crcpress.com/shopping_cart/products/product_detail.asp?sku=1184&isbn=0849311845&parent_id=&pc= L1 - http://www.biosciencenetbase.com/ejournals/books/book_summary/summary.asp?id=4747 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 - Hypothalamic neuropeptides and regulation of fat mass in Prader-Willi syndrome A1 - AP Goldstone A1 - UA Unmehopa A1 - Thomas EL A1 - AE Brynes A1 - JD Bell A1 - G Frost A1 - MA Ghatei A1 - A Holland A1 - SR Bloom A1 - DF Swaab ED - U Eiholzer, D l’Allemand, W Zipf T2 - Prader-Willi Syndrome as a Model for Obesity Y1 - 2003/// PB - Karger CY - Basel SN - 3805575742 SP - 31 EP - 43 N2 - - ER - TY - CHAP T1 - Fetal arrhythmias, Cardiac Malformations A1 - Gardiner HM ED - Hill LM; Mohammed K; Stone P; van Wijngaarden W; James DK T2 - Evidence based obstetrics Y1 - 2003/// PB - WB Saunders SP - 87 EP - 93 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 - Modélisation et chirurgie assistée par ordinateur A1 - Troccaz, J A1 - Luboz, V A1 - Chabanas, M A1 - Fleute, M A1 - Payan, Y A1 - Desbat, L ED - Elsevier T2 - Modélisation et chirurgie assistée par ordinateur Y1 - 2003/// CY - Monographie - Conférence d'Enseignement de la SOFCOT 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 - Metabolic disorders of the newborn A1 - Patay Z A1 - Robertson NJ A1 - Cox IJ ED - Rutherford MA T2 - Magnetic Resonance Imaging of the Neonatal Brain Y1 - 2002/// PB - WB Saunders SN - 07020 25348 SP - 315 EP - 348 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 - Magnetic resonance spectroscopy of the neonatal brain A1 - Robertson NJ A1 - Cox IJ ED - Rutherford MA T2 - Magnetic Resonance Imaging of the Neonatal Brain Y1 - 2002/// PB - WB Saunders SN - 07020 25348 SP - 295 EP - 314 N2 - - ER - TY - CHAP T1 - Hypoxic-ischaemic encephalopathy A1 - Edwards AD A1 - Mehmet H A1 - Hagberg H T2 - The newborn brain;neuroscience and clinical applications Y1 - 2002/// SN - 0-5217-9338-6 SP - 385 EP - 414 N2 - - ER - TY - CHAP T1 - Movement disorders: functional imaging A1 - Brooks DJ T2 - Parkinson's disease and movement disorders Y1 - 2002/// M2 - 4th SN - 0-7817-3515-7 SP - 95 EP - 110 N2 - - ER - TY - CHAP T1 - Apoptosis and necrosis in perinatal brain injury A1 - Edwards AD A1 - Mehmet H T2 - Birth asphyxia and the brain: basic science and clinical implications Y1 - 2002/// M2 - 7 SN - 0-8799-3499-9 SP - 135 EP - 152 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 - The magnetic resonance imaging appearances of the normal infant brain from term to two years. A1 - Cowan FM ED - Rutherford M A T2 - MR of the Neonatal Brain. Y1 - 2002/// PB - Harcourt Health Sciences CY - London N2 - - ER - TY - CHAP T1 - Physiology of the Developing Human Fetal Heart A1 - Gardiner HM ED - Anderson RH; Baker EJ; Macartney FJ; Rigby ML; Shinebourne EA; Tynan M T2 - Paediatric Cardiology Y1 - 2002/// M2 - 2nd Edition PB - Churchill Livingstone CY - London SP - 655 EP - 686 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 - Imaging Huntington's disease A1 - Brooks DJ A1 - Andrews T T2 - Huntington's disease Y1 - 2002/// M2 - 3rd SN - 0-1985-1060-8 SP - 95 EP - 110 N2 - - ER - TY - CHAP T1 - Laser and focused ultrasound ablation of primary and secondary liver tumours A1 - Dick EA A1 - Taylor-Robinson SD A1 - Gedroyc WM T2 - Multi-treatment modalities of liver tumours Y1 - 2002/// SN - 0-3064-6746-1 SP - 197 EP - 210 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 - 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 - Xenotransplantation: will pigs fly? A1 - George, AJT A1 - Lechler RI T2 - Future Strategies for Tissue and Organ Replacement Y1 - 2002/// SN - 1-8609-4311-X SP - 215 EP - 236 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 - Guiding therapeutic procedures A1 - Edwards PJ A1 - Hawkes DJ A1 - Penney GP A1 - Clarkson MJ ED - Jo Hajnal, David J Hawkes, Derek LG Hill T2 - Medical Image Registration Y1 - 2001/// PB - CRC Press 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 - Liver in vivo magnetic resonance spectroscopy of humans. A1 - Cox IJ ED - Young IR, Grant DM, Harris RK. T2 - Methods in Biomedical Magnetic Resonance Imaging and Spectroscopy Y1 - 2000/10// PB - John Wiley & Sons CY - Chichester SN - 0471-98804-9 N2 - - ER - TY - CHAP T1 - The antibody molecule A1 - George AJT ED - George AJT and Urch CE T2 - Diagnostic and Therapeutic Antibodies Y1 - 2000/// PB - Humana Press CY - Totowa, NJ SP - 1 EP - 21 N2 - - ER - TY - CHAP T1 - Outcome after intrapartum asphyxia in term infants. A1 - Cowan F T2 - Seminars in Neonatology Y1 - 2000/// M2 - 5 SP - 127 EP - 140 N2 - - ER - TY - CHAP T1 - Use of biosensors to measure the kinetics of antibody-antigen interactions A1 - George AJT ED - George AJT and Urch CE T2 - Diagnostic and Therapeutic Antibodies Y1 - 2000/// PB - Humana Press CY - Totowa NJ SP - 363 EP - 372 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 - Changes in the fetal and placental circulations associated with IUGR in humans A1 - Maršál K A1 - Gardiner HM ED - O’Brien PMS; Wheeler T; Barker DJP T2 - Fetal Programming: Influences on development and disease in later life Y1 - 1999/// PB - London: RCOG SP - 349 EP - 364 N2 - - ER - TY - CHAP T1 - Sedation for Magnetic Sedation for Magnetic Resonance Scanning of Infants and Young Children. A1 - Cowan FM ED - Whitwam JG & McCloy RF. T2 - Principles and Practice of Sedation. Y1 - 1998/// PB - Blackwell Healthcare CY - London SP - 206 EP - 213 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 - Magnetic resonance imaging of the neonatal brain. A1 - Maalouf E A1 - Counsell S A1 - Battin M A1 - Cowan F T2 - British Journal of Hospital Medicine Y1 - 1998/// M2 - 59 SP - 41 EP - 45 N2 - - ER - TY - CHAP T1 - Recent Advances in the management of the premature infant A1 - Mupanemunda R A1 - Azzopardi D ED - MG Elder, R Romero, RF Lamont T2 - Preterm Birth Y1 - 1997/// PB - Churchill Livingstone SN - 0-443-05857-1 N2 - - ER - TY - CONF T1 - Breathing Thorax Simulation based on Pleura Behaviour and Rib Kinematics A1 - Didier, AL A1 - Villard, PF A1 - Bayle, JY A1 - Beuve, M A1 - Shariat, B A2 - IEEE Computer Society Los Alamitos U1 - IEEE Information Visualisation AD - Zurich Y1 - 2007/// SP - 35 EP - 40 N2 - - UR - http://liris.cnrs.fr/publis/pdf/Shariat-2007_liris2801.pdf?id=2801 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 - Segmentation of cardiac MR and CT image sequences using model based registration of a 4D statistical model - art. no. 65121D A1 - Perperidis, D A1 - Mohiaddin, R A1 - Edwards, P A1 - Rueckert, D U1 - Medical Imaging 2007 Conference Y1 - 2007/// Y2 - // VL - 6512 SP - D5121 EP - D5121 N2 - - ER - TY - CONF T1 - Quantifying brain development in early childhood using segmentation and registration - art. no. 65120O A1 - Aljabar, P A1 - Bhatia, KK A1 - Murgasova, M A1 - Hajnal, JV A1 - Boardman, JP A1 - Srinivasan, L A1 - Rutherford, MA A1 - Dyet, LE A1 - Edwards, AD A1 - Rueckert, D U1 - Medical Imaging 2007 Conference Y1 - 2007/// Y2 - // VL - 6512 SP - O5120 EP - O5120 N2 - - ER - TY - CONF T1 - Automatic Extraction and Matching of Neonatal Cerebral Vasculature A1 - Xue H A1 - Malamateniou C A1 - Allsop J A1 - Srinivasan L A1 - Hajnal J A1 - Rueckert D U1 - IEEE International Symposium on Biomedical Imaging Y1 - 2006/04// PB - IEEE SP - 125 EP - 128 N2 - - UR - http://pubs.doc.ic.ac.uk/isbi-06-neonatal-vasculature ER - TY - CONF T1 - Analysis of Growth in the Developing Brain Using Non-Rigid Registration A1 - Aljabar P A1 - Bhatia KK A1 - Hajnal J A1 - Boardman J A1 - Srinivasan L A1 - Rutherford M A1 - Dyet L A1 - Edwards A A1 - Rueckert D U1 - IEEE International Symposium on Biomedical Imaging Y1 - 2006/04// PB - IEEE SP - 201 EP - 204 N2 - - UR - http://pubs.doc.ic.ac.uk/isbi-06-brain-growth ER - TY - CONF T1 - Neuroprotection with hypothermia following birth asphyxia A1 - Azzopardi, D U1 - 20th European Congress of Perinatal Medicine Y1 - 2006/// Y2 - // SP - 221 EP - 229 N2 - - ER - TY - CONF T1 - A novel approach to accurate 3D high resolution and high SNR fetal brain imaging A1 - Jiang, SZ A1 - Xue, H A1 - Glover, A A1 - Rutherford, M A1 - Hajnal, JV U1 - 3rd IEEE International Symposium on Biomedical Imaging Y1 - 2006/// Y2 - // SP - 662 EP - 665 N2 - - ER - TY - CONF T1 - An Approach to Convert 4D Geometry into a 4D CT Scan A1 - Villard, PF A1 - Beuve, M A1 - Shariat, B U1 - WSCG (Winter School of Computer Graphics) AD - Plzen (Czech Republic) Y1 - 2006/// SP - 163 EP - 170 N2 - - UR - http://liris.cnrs.fr/publis/pdf/Shariat-2006_liris2299.pdf?id=2299 ER - TY - CONF T1 - Whole brain morphometric analysis of changes associated with pre-term birth - art. no. 61445Y A1 - Thomaz, CE A1 - Boardman, JP A1 - Counsell, S A1 - Hill, DLG A1 - Hajnal, JV A1 - Edwards, AD A1 - Rutherford, MA A1 - Gillies, DF A1 - Rueckert, D U1 - Medical Imaging 2006 Conference Y1 - 2006/// Y2 - // VL - 6144 SP - Y1445 EP - Y1445 N2 - - ER - TY - CONF T1 - Visualisation of Physical Lung Simulation: an Interactive Application to Assist Physicians A1 - Villard, PF A1 - Fournier, G A1 - Beuve, M A1 - Shariat, B A2 - IEEE Computer Society Los Alamitos U1 - IEEE Information Visualisation AD - London Y1 - 2006/// SP - 65 EP - 70 N2 - - UR - http://liris.cnrs.fr/publis/pdf/Shariat-2006_liris2416.pdf?id=2416 ER - TY - CONF T1 - The Challenges of developing a collaborative data and compute grid for Neurosciences A1 - Geddes, J A1 - Mackay, C A1 - Lloyd, S A1 - Simpson, A A1 - Power, D A1 - Russell, D A1 - Katzarova, M A1 - Rossor, M A1 - Fox, N A1 - Fletcher, J A1 - Hill, D A1 - McLeish, K A1 - Hajnal, JV A1 - Lawrie, S A1 - Job, D A1 - McIntosh, A A1 - Wardlaw, J A1 - Sandercock, P A1 - Palmer, J A1 - Perry, D A1 - Procter, R A1 - Ure, J A1 - Bath, P A1 - Watson, G U1 - 19th IEEE Symposium on Computer-Based Medical Systems Y1 - 2006/// Y2 - // SP - 81 EP - 86 N2 - - ER - TY - CONF T1 - Cell-type specific experience-dependent structural plasticity of axonal branches and boutons in the adult neocortex. A1 - De Paola, V. A1 - Song, S. A1 - Holtmaat, A. A1 - Wilbrecht, L. A1 - Knott, G. A1 - Caroni, P. A1 - Svoboda, K. U1 - EMBO Fellows meeting AD - La Jolla, USA Y1 - 2006/// N2 - - ER - TY - CONF T1 - Lung 4D CT scan Generation A1 - Villard, PF A1 - Beuve, M A1 - Shariat, B U1 - 2nd Workshop on Computer Assisted Diagnosis and Surgery AD - Santiago (Chile) Y1 - 2006/// SP - 47 EP - 50 N2 - - UR - http://liris.cnrs.fr/publis/pdf/Shariat-2006_liris2300.pdf?id=2300 ER - TY - CONF T1 - Cell-type specific experience-dependent structural plasticity of axonal branches and boutons in the adult neocortex. A1 - De Paola, V. A1 - Song, S. A1 - Holtmaat, A. A1 - Wilbrecht, L. A1 - Knott, G. A1 - Caroni, P. A1 - Svoboda, K. U1 - FENS 2006 AD - Vienna, Austria Y1 - 2006/// N2 - - ER - TY - CONF T1 - Central nervous system involvement in hepatitis C virus infection: what to measure? A1 - Forton, DM A1 - Allsop, J A1 - Thomas, HC A1 - Taylor-Robinson, SD U1 - 12th International Symposium on Hepatic Encephalopathy and Nitrogen Metabolism Y1 - 2006/// Y2 - // SP - 284 EP - 290 N2 - - ER - TY - CONF T1 - Long-term 2-photon imaging of cortical axons and their boutons in adult mice. A1 - De Paola, V. A1 - Song, S. A1 - Holtmaat, A. A1 - Wilbrecht, L., A1 - Knott, G. A1 - Caroni, P. U1 - Imaging Neurons and Neural Activity: New Methods, New Results. AD - Cold Spring Harbor Laboratory, NY, USA Y1 - 2005/// N2 - - ER - TY - CONF T1 - Validation of PET imaging by alignment to histology slices A1 - Edwards PJ A1 - Nijmeh AD A1 - McGurk M A1 - Odell E A1 - Fenlon MR A1 - Marsden PK A1 - Hawkes DJ A2 - James S. Duncan, Guido Gerig U1 - MICCAI AD - Palm Springs J1 - Lecture Notes in Computer Science Y1 - 2005/// Y2 - 2005/10/26/ VL - 3750 PB - Springer Verlag CY - Berlin Heidelberg SN - 0302-9743 SP - 968 EP - 975 N2 - - ER - TY - CONF T1 - Simulation of Lung Behaviour with Finite Elements : Influence of Bio-Mechanical Parameters A1 - Villard, PF A1 - Beuve, M A1 - Shariat, B A1 - Baudet, V A1 - Jaillet, F A2 - IEEE Computer Society Los Alamitos U1 - IEEE Information Visualisation AD - London Y1 - 2005/// SP - 9 EP - 14 N2 - - UR - http://liris.cnrs.fr/publis/pdf/Jaillet-2005_liris1800.pdf?id=1800 ER - TY - CONF T1 - Resolution of Non-Linear Problems In Realistic-Lung-Inflating Simulation with Finite Element Method A1 - Villard, PF A1 - Beuve, M A1 - Shariat, B A1 - Baudet, V A1 - Jaillet, F U1 - 10th workshop on Heavy Charged Particles in Biology and Medicine AD - Oropa (Italy) Y1 - 2005/// SP - 184 EP - 187 N2 - - ER - TY - CONF T1 - Propagating labels of the human brain based on non-rigid MR image registration: an evaluation A1 - Heckemann, RA A1 - Hajnal, JV A1 - Rueckert, D A1 - Hill, DLG A1 - Hammers, A U1 - Medical Imaging 2005 Conference Y1 - 2005/// Y2 - // VL - 5747 SP - 1864 EP - 1871 N2 - - ER - TY - CONF T1 - Dendritic spine shape affects membrane-bound protein flux between the spine head and the dendritic shaft. A1 - S.Hugel A1 - V. De Paola A1 - P.Caroni A1 - B.H.Gahwiler A1 - R.A.McKinney U1 - Society for Neuroscience Meeting AD - Washington, DC, USA Y1 - 2005/// N2 - - ER - TY - CONF T1 - NeuroGrid: Using grid technology to advance neuroscience A1 - Geddes, J A1 - Lloyd, S A1 - Simpson, A A1 - Rossor, M A1 - Fox, N A1 - Hill, D A1 - Hajnal, JV A1 - Lawrie, S A1 - McIntosh, A A1 - Johnstone, E A1 - Wardlaw, J A1 - Perry, D A1 - Procter, R A1 - Bath, P A1 - Bullmore, E U1 - 18th IEEE Symposium on Computer-Based Medical Systems Y1 - 2005/// Y2 - // SP - 570 EP - 572 N2 - - ER - TY - CONF T1 - Long-term imaging of pre-synaptic terminals in the adult somatosensory cortex in vivo. A1 - De Paola, V. A1 - Song, S A1 - Holtmaat, A. A1 - Wilbrecht, L. A1 - Caroni, P. A1 - Svoboda, K. U1 - Society for Neuroscience Meeting. AD - San Diego, California, USA Y1 - 2004/// N2 - - ER - TY - CONF T1 - Analysis of serial MR images of joints A1 - Leung, KK A1 - Heckemann, RA A1 - Saeed, N A1 - Brooks, KJ A1 - Buckton, JB A1 - Changani, K A1 - Reid, DG A1 - Rueckert, D A1 - Hajnal, JV A1 - Holden, M A1 - Hill, DLG U1 - 2nd IEEE International Symposium on Biomedical Imaging Y1 - 2004/// Y2 - // SP - 221 EP - 224 N2 - - ER - TY - CONF T1 - Using a maximum uncertainly LDA-based approach to classify and analyse MR brain images A1 - Thomaz CE A1 - Boardman JP A1 - Hill D A1 - Hajnal JV A1 - Edwards AD A1 - Rutherford M A1 - Rueckert D U1 - MICCAI Conference Y1 - 2004/// Y2 - 2004/// N2 - - ER - TY - CONF T1 - Augmented reality provision in robotically assisted minimally invasive surgery A1 - Wang, DA A1 - Bello, F A1 - Darzi, A U1 - 18th International Congress and Exhibition on Computer Assisted Radiology and Surgery (CARS 2004) Y1 - 2004/// Y2 - // VL - 1268 SP - 527 EP - 532 N2 - - ER - TY - CONF T1 - Consistent groupwise non-rigid registration for atlas construction A1 - Bhatia K A1 - Hajnal JV A1 - Puri BK A1 - Edwards AD A1 - Rueckert D U1 - MICCAI Conference Y1 - 2004/// Y2 - 2004/// N2 - - ER - TY - CONF T1 - In vivo imaging of cortical axon dynamics during early postnatal development reveals long-range growth and pruning prior to stable bouton formation. A1 - C.Portera-Cailliau A1 - V. De Paola A1 - P.Caroni A1 - R.Yuste A1 - K.Svoboda U1 - Society for Neuroscience Meeting. AD - San Diego, California, USA Y1 - 2004/// 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 - Modelisation of Target Motion and Organ Deformation : Lung Tumour Tracking. A1 - Baudet, V A1 - Villard, PF A1 - Beuve, M A1 - Shariat, B U1 - 9th workshop HCPBM AD - Lyon (Fr) Y1 - 2003/// N2 - - ER - TY - CONF T1 - Reduced pallidal magnetisation transfer ratios are associated with fatigue in pre-cirrhotic patients with primary biliary cirrhosis A1 - Forton, DM A1 - Prince, M A1 - Allsop, J A1 - Patel, N A1 - Goldblatt, J A1 - Thomas, HC A1 - Bassendine, M A1 - Jones, DEJ A1 - Taylor-Robinson, SD U1 - 11th International Symposium on Hepatic Encephalopathy and Nitrogen Metabolism Y1 - 2003/// Y2 - // SP - 173 EP - 174 N2 - - ER - TY - CONF T1 - ROVIMAS: A software package for assessing surgical skills using the da Vinci telemanipulator system A1 - Dosis, A A1 - Bello, F A1 - Rockall, T A1 - Munz, Y A1 - Moorthy, K A1 - Martin, S A1 - Darzi, A U1 - 4th International Conference on Information Technology Applications in Biomedicine (ITAB 2003) Y1 - 2003/// Y2 - // SP - 326 EP - 329 N2 - - ER - TY - CONF T1 - Current issues of photorealistic rendering for virtual and augmented reality in minimally invasive surgery A1 - Stoyanov, D A1 - ElHelw, M A1 - Lo, BP A1 - Chung, A A1 - Bello, F A1 - Yang, GZ U1 - 7th International Conference on Information Visualization (IV 2003) Y1 - 2003/// Y2 - // SP - 350 EP - 358 N2 - - ER - TY - CONF T1 - Evaluation of the exophthalmia reduction with a finite element model A1 - Luboz, V A1 - Pedrono, A A1 - Boutault, F A1 - Swider, P A1 - Payan, Y U1 - 16th International Congress and Exhibition on Computer Assisted Radiology and Surgery Y1 - 2002/// Y2 - // SP - 1123 EP - 1123 N2 - - ER - TY - CONF T1 - High Resolution Visualization of Synaptic Morphology and Dynamics in Transgenic Mice Expressing GFP-Fusion Proteins In Single Neurons. A1 - De Paola, V. A1 - Sadhu, A. A1 - Pajusola, K. A1 - Pun, S. A1 - Xu, L. A1 - Arber, S. A1 - McKinney, R.A. A1 - Caroni, P. U1 - EMBO/FMI Conference. Organizing the Brain: Genes, Neurons, and Circuits. AD - Ascona, Switzerland Y1 - 2002/// 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 - Movement disorders: An overview A1 - Brooks, DJ U1 - 1st Solvay Pharmaceuticals Conference Y1 - 2002/// Y2 - // VL - 1 SP - 5 EP - 13 N2 - - ER - TY - CONF T1 - Use of ultrasound contrast agents in hepatology A1 - Lim, AKP A1 - Harvey, CJ A1 - Taylor-Robinson, SD A1 - Blomley, MJK A1 - Cosgrove, DO U1 - Falk Symposium on Medical Imaging in Gastroenterology and Hepatology Y1 - 2002/// Y2 - // VL - 124 SP - 132 EP - 139 N2 - - ER - TY - CONF T1 - Glutamate spillover triggers changes in synaptic connectivity. A1 - D. Richards A1 - V. De Paola A1 - P. Caroni A1 - B. Gähwiler A1 - R.A. McKinney U1 - Society for Neuroscience Meeting AD - Orlando, Florida, USA Y1 - 2002/// N2 - - ER - TY - CONF T1 - Virtual reality surgical training and assessment system A1 - Paloc, C A1 - Kitney, RI A1 - Bello, F A1 - Darzi, A U1 - 15th International Congress and Exhibition on Computer Assisted Radiology and Surgery Y1 - 2001/// Y2 - // VL - 1230 SP - 207 EP - 212 N2 - - ER - TY - CONF T1 - Presynaptic terminal dynamics in mature hippocampal networks. A1 - De Paola, V. A1 - Caroni, P. U1 - USGEB Young Investigator Meeting AD - Lausanne, Switzerland Y1 - 2001/// N2 - - ER - TY - CONF T1 - Algorithm for retrieval of deep brain temperature in new-born infant from microwave radiometric data A1 - Mizushina, S A1 - Maruyma, K A1 - Sugiura, T A1 - Van Leeuwen, GMJ A1 - Hand, JW A1 - Marrocco, G A1 - Bardati, F A1 - Edwards, AD A1 - Azzopardi, D A1 - Land, D U1 - IEEE MTT-S International Microwave Symposium (IMS2000) Y1 - 2000/// Y2 - // SP - 1033 EP - 1036 N2 - - ER - TY - CONF T1 - Transgenic mice expressing GFP fusion proteins in adult neurons of the central and peripheral nervous system. A1 - De Paola, V. A1 - Caroni, P. U1 - EMBO/FMI Conference. Neuronal Circuits: From Molecules to Organisms. AD - Ascona, Switzerland Y1 - 1999/// 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 - PET studies in neuropharmacology. Novel approaches. A1 - Brooks, DJ U1 - NATO Advanced Research Workshop on Positron Emission Tomography - A Critical Assessment of Recent Trends Y1 - 1998/// Y2 - // VL - 51 SP - 239 EP - 248 N2 - - ER - TY - CONF T1 - Methodology for statistical parametric mapping of [F-18]fluorodopa uptake rate using three-dimensional PET A1 - Rakshi, JS A1 - Bailey, DL A1 - Ito, K A1 - Uema, T A1 - Morrish, PK A1 - Ashburner, J A1 - Friston, KJ A1 - Brooks, DJ U1 - 3rd International Conference on Quantification of Brain Function with PET (BRAINPET 97) Y1 - 1998/// Y2 - // SP - 117 EP - 123 N2 - - ER - TY - CONF T1 - Targeted-GFP expression in adult neurons of transgenic mice. A1 - De Paola, V. A1 - Caroni, P. U1 - 2nd Swiss Meeting on Muscle Research AD - Macolin, Switzerland Y1 - 1998/// N2 - - 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 - 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 - Relationship between white matter apparent diffusion coefficients in preterm infants at term-equivalent age and developmental outcome at 2 years. A1 - Krishnan, ML A1 - Dyet, LE A1 - Boardman, JP A1 - Kapellou, O A1 - Allsop, JM A1 - Cowan, F A1 - Edwards, AD A1 - Rutherford, MA A1 - Counsell, SJ J1 - Pediatrics Y1 - 2007/09// VL - 120 SN - 1098-4275 SP - e604 EP - e609 N2 - OBJECTIVE: The aim of this study was to develop a simple reproducible method for the measurement of apparent diffusion coefficient values in the white matter of preterm infants using diffusion-weighted imaging to test the hypothesis that elevated mean apparent diffusion coefficient values are associated with lower developmental quotient scores at 2 years' corrected age. METHODS: We obtained diffusion-weighted imaging in 38 preterm infants at term-equivalent age who had no evidence of overt cerebral pathology on conventional MRI. Mean apparent diffusion coefficient values at the level of the centrum semiovale were determined. The children were assessed using a standardized neurologic examination, and the Griffiths Mental Development Scales were administered to obtain a developmental quotient at 2 years' corrected age. The relationship between mean apparent diffusion coefficient values and developmental quotient was examined. Clinical data relating to postnatal sepsis, antenatal steroid exposure, supplemental oxygen, gender, patent ductus arteriosus, and inotrope requirement were collected, and the mean apparent diffusion coefficient values for each group were compared. RESULTS: The mean (+/-SD) apparent diffusion coefficient value in the white matter was 1.385 +/- 0.07 x 10(-3) mm2/second, and the mean developmental quotient was 108.9 +/- 11.5. None of the children had a significant neurologic problem. There was a significant negative correlation between mean apparent diffusion coefficient and developmental quotient. CONCLUSION: These findings suggest that higher white matter apparent diffusion coefficient values at term-equivalent age in preterm infants without overt lesions are associated with poorer developmental performance in later childhood. Consequently, apparent diffusion coefficient values at term may be of prognostic value for neurodevelopmental outcome in infants who are born preterm and who have no other imaging indicators of abnormality. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17698966&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 - 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 - Application of magnetic resonance methods to studies of gene therapy A1 - So, PW A1 - Parkes, HG A1 - Bell, JD J1 - PROG NUCL MAG RES SP Y1 - 2007/08/30/ VL - 51 SN - 0079-6565 SP - 49 EP - 62 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 - Should cranial MRI screening of preterm infants become routine? A1 - de Vries, LS A1 - Cowan, FM J1 - Nat Clin Pract Neurol Y1 - 2007/08/28/ SN - 1745-8358 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17724489&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 - 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 - Early growth in brain volume is preserved in the majority of preterm infants. A1 - Boardman, JP A1 - Counsell, SJ A1 - Rueckert, D A1 - Hajnal, JV A1 - Bhatia, KK A1 - Srinivasan, L A1 - Kapellou, O A1 - Aljabar, P A1 - Dyet, LE A1 - Rutherford, MA A1 - Allsop, JM A1 - Edwards, AD J1 - Ann Neurol Y1 - 2007/08/14/ SN - 0364-5134 N2 - OBJECTIVE: Preterm infants have reduced cerebral tissue volumes in adolescence. This study addresses the question: Is reduced global brain growth in the neonatal period inevitable after premature birth, or is it associated with specific medical risk factors? METHODS: Eighty-nine preterm infants at term equivalent age without focal parenchymal brain lesions were studied with 20 full-term control infants. Using a deformation-based morphometric approach, we transformed images to a reference anatomic space, and we used the transformations to calculate whole-brain volume and ventricular volume for each subject. Patterns of volume difference were correlated with clinical data. RESULTS: Cerebral volume is not reduced compared with term born control infants (p = 0.765). Supplemental oxygen requirement at 28 postnatal days is associated with lower cerebral tissue volume at term (p < 0.001), but there were no significant differences in cerebral volumes attributable to perinatal sepsis (p = 0.515) and quantitatively defined diffuse white matter injury (p = 0.183). As expected, the ventricular system is significantly larger in preterm infants at term equivalent age compared with term control infants (p < 0.001). INTERPRETATION: Cerebral volume is not reduced during intensive care for the majority of preterm infants, but prolonged supplemental oxygen dependence is a risk factor for early attenuation of global brain growth. The reduced cerebral tissue volume seen in adolescents born preterm does not appear to be an inevitable association of prematurity, but rather caused by either specific disease during intensive care or factors operating beyond the neonatal period. Ann Neurol 2007. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17696128&query_hl=1 ER - TY - JFULL T1 - In-utero intervention for severe congenital heart disease. A1 - Gardiner, HM J1 - Best Pract Res Clin Obstet Gynaecol Y1 - 2007/08/11/ SN - 1521-6934 N2 - The concept of fetal therapy is well established for many disorders diagnosed before birth but practical issues regarding its introduction into clinical practice are more difficult. Cardiac malformations are common, with major lesions affecting about 3.5 per thousand pregnancies; however, only a small proportion of these is likely to benefit from an intrauterine intervention. In addition, there are no good animal models of human cardiac disease and our knowledge of the underlying mechanisms is at best sketchy. This combination of factors has resulted in slow progress in developing effective therapies for the intrauterine management of cardiac disease. Recent research and clinical developments have included percutaneous valvuloplasty for severe aortic and pulmonary stenosis, perforation of the closed or restrictive inter-atrial septum and pacing for complete heart block. Progress in these endeavours has been variable but - overall - shows promise for treatment of the human fetus. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17697798&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 - Using multimedia and Web3D to enhance anatomy teaching A1 - Brenton, H A1 - Hernandez, J A1 - Bello, F A1 - Strutton, P A1 - Purkayastha, S A1 - Firth, T A1 - Darzi, A J1 - COMPUT EDUC Y1 - 2007/08// VL - 49 SN - 0360-1315 SP - 32 EP - 53 N2 - Anatomy teaching is undergoing significant changes due to time constraints, limited availability of cadavers and technological developments in the areas of three-dimensional modelling and computer-assisted learning. This paper gives an overview of methods used to teach anatomy to undergraduate medical students and discusses the educational advantages and disadvantages of using three-dimensional computer models. A 'work in progress' account is then given of a project to develop two Web3D resources to enhance undergraduate tuition of the nervous system. Our approach is to support existing curricula using advanced modelling tools and a variety of delivery mechanisms.The first resource is a three-dimensional model of the adult brachial plexus: a network of nerves extending from the neck down to the shoulder, arm, hand, and fingers. This will be incorporated into existing didactic classroom teaching under the supervision of an anatomy teacher. The second resource is a piece of online courseware which will teach the embryological development of the brachial plexus. The delivery method will be the WebSET framework, a collaborative environment that allows a teacher to manipulate 3D models over the Web in real time whilst providing explanation and help to students. In this way the courseware can be used for both self-directed study and 'virtual anatomy demonstrations' within an online peer group. (c) 2005 Elsevier Ltd. All rights reserved. ER - TY - JFULL T1 - Sylvian fissure morphology in Prader-Willi syndrome and early-onset morbid obesity. A1 - Miller, JL A1 - Couch, JA A1 - Leonard, CM A1 - Schwenk, K A1 - Towler, SD A1 - Shuster, J A1 - Goldstone, AP A1 - He, G A1 - Driscoll, DJ A1 - Liu, Y J1 - Genet Med Y1 - 2007/08// VL - 9 SN - 1098-3600 SP - 536 EP - 543 N2 - PURPOSE: Prader-Willi syndrome is a well-defined genetic cause of childhood-onset obesity that can serve as a model for investigating early-onset childhood obesity. Individuals with Prader-Willi syndrome have speech and language impairments, suggesting possible involvement of the perisylvian region of the brain. Clinical observations suggest that many individuals with early-onset morbid obesity have similar speech/language deficits, indicating possible perisylvian involvement in these children as well. We hypothesized that similar perisylvian abnormalities may exist in both disorders. METHODS: Participants included individuals with Prader-Willi syndrome (n = 27), their siblings (n = 16), individuals with early-onset morbid obesity (n = 13), and their siblings (n = 10). Quantitative and qualitative assessments of sylvian fissure conformation, insula closure, and planum temporale length were performed blind to hemisphere and diagnosis. RESULTS: Quantitative measurements verified incomplete closure of the insula in individuals with Prader-Willi syndrome. Planar asymmetry showed its normal bias toward leftward asymmetry in all groups except those with Prader-Willi syndrome maternal uniparental disomy. Individuals with Prader-Willi syndrome and siblings had a normal distribution of sylvian fissure types in both hemispheres, while individuals with early-onset morbid obesity and their siblings had a high proportion of rare sylvian fissures in the right hemisphere. CONCLUSIONS: The contrast between the anatomic findings in individuals with Prader-Willi syndrome and early-onset morbid obesity suggests that the language problems displayed by children with these two conditions may be associated with different neurodevelopmental processes. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17700392&query_hl=1 ER - TY - JFULL T1 - Hypothermia. A1 - Azzopardi, D A1 - Edwards, AD J1 - Semin Fetal Neonatal Med Y1 - 2007/08// VL - 12 SN - 1744-165X SP - 303 EP - 310 N2 - Experimental studies show that, following hypoxic ischaemic injury, mild induced hypothermia-a reduction of body temperature by about 3 degrees C -- preserves cerebral energy metabolism, reduces cerebral tissue injury and improves neurological function. Randomized trials in full-term and near-full-term newborns suggest that treatment with mild hypothermia is safe and improves survival without disabilities up to 18 months of age. Although the optimal time of initiation, the depth and duration, and the method of cooling are uncertain, in the absence of specific treatments many clinicians will wish to consider treating asphyxiated infants with hypothermia. Guidance now needs to be provided to promote uniform practice, to avoid inappropriate treatment and to foster continuing collaboration in future studies of neuroprotection following asphyxia. If the promising results of the current trials are confirmed by the findings from other on-going studies, with longer follow-up, the impact of such a treatment on the babies, their families and health resources in the shorter and longer terms will be considerable. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17392043&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 - 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 - 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 - Cranial Ultrasound in Metabolic Disorders Presenting in the Neonatal Period: Characteristic Features and Comparison with MR Imaging. A1 - Leijser, LM A1 - de Vries, LS A1 - Rutherford, MA A1 - Manzur, AY A1 - Groenendaal, F A1 - de Koning, TJ A1 - van der Heide-Jalving, M A1 - Cowan, FM J1 - AJNR Am J Neuroradiol Y1 - 2007/08// VL - 28 SN - 0195-6108 SP - 1223 EP - 1231 N2 - BACKGROUND AND PURPOSE: Brain imaging is an integral part of the diagnostic work-up for metabolic disorders, and the bedside availability of cranial ultrasonography (cUS) allows very early brain imaging in symptomatic neonates. Our aim was to investigate the role and range of abnormalities seen on cUS in neonates presenting with metabolic disorders. A secondary aim, when possible, was to address the question of whether brain MR imaging is more informative by comparing cUS to MR imaging findings. MATERIALS AND METHODS: Neonates with a metabolic disorder who had at least 1 cUS scan were eligible. cUS images were reviewed for anatomic and maturation features, cysts, calcium, and other abnormalities. When an MR imaging scan had been obtained, both sets of images were compared. RESULTS: Fifty-five infants (35 also had MR imaging) were studied. The most frequent findings were in oxidative phosphorylation disorders (21 cUS and 12 MR imaging): ventricular dilation (11 cUS and 6 MR imaging), germinolytic cysts (GLCs; 7 cUS and 5 MR imaging), and abnormal white matter (7 cUS and 6 MR imaging); in peroxisomal biogenesis disorders (13 cUS and 9 MR imaging): GLCs (10 cUS and 6 MR imaging), ventricular dilation (10 cUS and 5 MR imaging), abnormal cortical folding (8 cUS and 7 MR imaging), and lenticulostriate vasculopathy (8 cUS); in amino acid metabolism and urea cycle disorders (14 cUS and 11 MR imaging): abnormal cortical folding (9 cUS and 4 MR imaging), abnormal white matter (8 cUS and 8 MR imaging), and hypoplasia of the corpus callosum (7 cUS and 6 MR imaging); in organic acid disorders (4 cUS and 2 MR imaging): periventricular white matter echogenicity (2 cUS and 1 MR imaging); and in other disorders (3 cUS and 1 MR imaging): ventricular dilation (2 cUS and 1 MR imaging). cUS findings were consistent with MR imaging findings. cUS was better for visualizing GLCs and calcification. MR imaging was more sensitive for subtle tissue signal intensity changes in the white matter and abnormality in areas difficult to visualize with cUS, though abnormalities of cortical folding suggestive of polymicrogyria were seen on cUS. CONCLUSION: A wide range of abnormalities is seen using cUS in neonatal metabolic disorders. cUS is a reliable bedside tool for early detection of cysts, calcium, structural brain abnormalities, and white matter echogenicity, all suggestive of metabolic disorders. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17698520&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 - Balancing bias, reliability, noise properties and the need for parametric maps in quantitative ligand PET: [(11)C]diprenorphine test-retest data. A1 - Hammers, A A1 - Asselin, MC A1 - Turkheimer, FE A1 - Hinz, R A1 - Osman, S A1 - Hotton, G A1 - Brooks, DJ A1 - Duncan, JS A1 - Koepp, MJ J1 - Neuroimage Y1 - 2007/07/24/ SN - 1053-8119 N2 - [(11)C]diprenorphine (DPN) is a non-subtype selective opioid receptor PET ligand with slow kinetics and no region devoid of specific binding. Parametric maps are desirable but have to overcome high noise at the voxel level. We obtained parameter values, parametric map image quality, test-retest reproducibility and reliability (using intraclass correlation coefficients (ICCs)) for conventional spectral analysis and a derived method (rank shaping), compared them with values obtained through sampling of volumes of interest (VOIs) on the dynamic data sets and tested whether smaller amounts of radioactivity injected maintained reliability. Ten subjects were injected twice with either approximately 185 MBq or approximately 135 MBq of [(11)C]DPN, followed by dynamic PET for 90 min. Data were movement corrected with a frame-to-frame co-registration method. Arterial plasma input functions corrected for radiolabelled metabolites were created. There was no overall effect of movement correction except for one subject with substantial movement whose test-retest differences decreased by approximately 50%. Actual parametric values depended heavily on the cutoff for slow frequencies (between 0.0008 s(-1) and 0.00063 s(-1)). Image quality was satisfactory for restricted base ranges when using conventional spectral analysis. The rank shaping method allowed maximising of this range but had similar bias. VOI-based methods had the widest dynamic range between regions. Average percentage test-retest differences were smallest for the parametric maps with restricted base ranges; similarly ICCs were highest for these (up to 0.86) but unacceptably low for VOI-derived VD estimates at the low doses of injected radioactivity (0.24/0.04). Our data can inform the choice of methodology for a given biological problem. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17764977&query_hl=1 ER - TY - JFULL T1 - MRI at 3 Tesla detects no evidence for ischemic brain damage in intensively treated patients with homozygous familial hypercholesterolemia. A1 - Schmitz, SA A1 - O'regan, DP A1 - Fitzpatrick, J A1 - Neuwirth, C A1 - Potter, E A1 - Tosi, I A1 - Hajnal, JV A1 - Naoumova, RP J1 - Neuroradiology Y1 - 2007/07/21/ SN - 0028-3940 N2 - INTRODUCTION: Homozygous familial hypercholesterolemia (FH) is considered a model disease for excessive plasma cholesterol levels. Patients with untreated homozygous FH have a markedly increased risk for premature atherosclerosis. The frequency and extent of ischemic brain damage detectable by high-field magnetic resonance imaging (MRI) after long-term intensive treatment are unknown. METHODS: In a case control study, five patients with homozygous FH (one male and four females; mean age: 23.6 +/- 9.2, range: 12-36 years; mean pre-treatment serum total cholesterol level: 26.9 +/- 3.24 mmol/L; all patients with documented atherosclerotic plaques in the carotid arteries) and five age- and sex-matched healthy controls were studied. All patients had been on maximal lipid-lowering medication since early childhood, and four of them were also on treatment with low-density lipoprotein (LDL) apheresis at bi-weekly intervals. Brain MRI was performed at 3 Tesla field strength with fluid-attenuated T2-weighted inversion recovery and T1-weighted spin-echo MR pulse sequences and subsequently evaluated by two independent readers. RESULTS: The maximal lipid-lowering treatment reduced the total serum cholesterol by more than 50% in the patients, but their serum concentrations were still 3.6-fold higher than those found in the controls (11.9 +/- 4.2 vs. 4.5 +/- 0.5 mmol/L; p < 0.0047). No brain abnormality was observed in any of the patients with homozygous FH. CONCLUSION: Homozygous FH patients on intensive cholesterol-lowering therapy have no evidence of ischemic brain damage at 3 Tesla MRI despite the remaining high cholesterol levels. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17643240&query_hl=1 ER - TY - JFULL T1 - Fluorescence lifetime tomography of live cells expressing enhanced green fluorescent protein embedded in a scattering medium exhibiting background autofluorescence. A1 - Soloviev, VY A1 - McGinty, J A1 - Tahir, KB A1 - Neil, MA A1 - Sardini, A A1 - Hajnal, JV A1 - Arridge, SR A1 - French, PM J1 - Opt Lett Y1 - 2007/07/15/ VL - 32 SN - 0146-9592 SP - 2034 EP - 2036 N2 - We present a novel fluorescence lifetime tomography system applied to a highly scattering autofluorescent phantom containing live cells expressing the fluorophore enhanced green fluorescent protein (EGFP). The fluorescence signal was excited using a fiber-laser-pumped supercontinuum source and detected using wide-field time gating imaging. To facilitate rapid 3D reconstruction of the fluorescence lifetime distribution, the time-resolved data were Fourier-transformed in time to give complex functions that formed a data set for the Fourier domain reconstruction. Initially the presence of an unspecified background autofluorescence signal impeded reconstruction of the lifetime distribution, but we show that this problem can be addressed using a simple iterative technique. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17632634&query_hl=1 ER - TY - JFULL T1 - Synthesis of a novel 'smart' bifunctional chelating agent 1-(2-[beta,D-galactopyranosyloxy]ethyl)-7-(1-carboxy-3-[4-aminophenyl]propyl)-4,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (Gal-PA-DO3A-NH2) and its Gd(III) complex. A1 - Wardle, NJ A1 - Herlihy, AH A1 - So, PW A1 - Bell, JD A1 - Bligh, SW J1 - Bioorg Med Chem Y1 - 2007/07/15/ VL - 15 SN - 0968-0896 SP - 4714 EP - 4721 N2 - A new synthetic pathway to 1-(2-[beta,D-galactopyranosyloxy]ethyl)-7-(1-carboxy-3-[4-aminophenyl]propyl)-4,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (Gal-PA-DO3A-NH2) and 1-(2-[beta,D-galactopyranosyloxy]ethyl)-4,7,10-tris(carboxymethyl)-1, 4,7,10-tetraazacyclododecane (Gal-DO3A) chelating agents was developed involving full hydroxyl- and carboxyl-group protection in precursors to product. Two sequences of cyclen-N-functionalisation were subsequently investigated, one successfully, towards synthesis of the novel 'smart' bifunctional Gal-PA-DO3A-NH2 chelate. The longitudinal proton relaxivities of the neutral [Gd-(Gal-PA-DO3A-NH2)] and [Gd-(Gal-DO3A)] complexes were increased by 28% and 37% in the presence of beta-galactosidase, respectively. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17512738&query_hl=1 ER - TY - JFULL T1 - MICROBUBBLE CONTRAST AGENT DETECTION USING BINARY CODED PULSES. A1 - Eckersley, RJ A1 - Tang, MX A1 - Chetty, K A1 - Hajnal, JV J1 - Ultrasound Med Biol Y1 - 2007/07/13/ SN - 0301-5629 N2 - Real-time visualization of microbubbles in the microvasculature of deep tissues remains a challenge for existing nonlinear microbubble imaging techniques. A technique with high sensitivity to nonlinear signals is required to compensate for the effects of limited power used to avoid bubble destruction and the high attenuation of the overlying tissues for deeper targets. The use of coded pulses in ultrasound imaging is well established as a means of improving the signal-to-noise ratio (SNR) within B-mode ultrasound imaging, but the feasibility of this approach for detecting microbubbles has not been well studied. In this work we investigate the use of binary phase encoding together with phase and amplitude modulation (PIAM) for the detection of nonlinear signals from microbubbles. A series of simulation experiments were conducted using a modified Rayleigh-Plesset model together with Golay and Barker coding techniques to investigate (i) the ability of binary encoded PIAM to detect nonlinear signals, (ii) the effect of the SNR and insonating pressure on the detection process, (iii) the sensitivity of different pulse encoding approaches and (iv) the effects of bubble resonance behavior on the detection process. The results show that the binary encoding approach combined with PIAM is able to detect nonlinear signals from microbubbles. It was found that nonlinear scattering from the microbubbles degrades the sensitivity of the binary encoded approach such that at high SNR there is no advantage in using these pulses over existing short-pulse PIAM. However, at lower SNR (<20 dB) the increased pulse length provides improved sensitivity without significant loss of spatial resolution, even under conditions in which the detection failed completely for existing approaches. The results also show that both the insonating acoustic pressure and resonance behavior of bubbles have an effect on the detection sensitivity and spatial resolution for the binary encoded approach. (E-mail: r.eckersley@imperial.ac.uk). L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17629609&query_hl=1 ER - TY - JFULL T1 - Microglial activation in presymptomatic Huntington's disease gene carriers. A1 - Tai, YF A1 - Pavese, N A1 - Gerhard, A A1 - Tabrizi, SJ A1 - Barker, RA A1 - Brooks, DJ A1 - Piccini, P J1 - Brain Y1 - 2007/07// VL - 130 SN - 1460-2156 SP - 1759 EP - 1766 N2 - Microglial activation may play a role in the pathogenesis of Huntington's disease (HD). Using 11C-(R)-PK11195 (PK) positron emission tomography (PET), we investigated microglial activation in HD presymptomatic gene carriers (PGCs), its relationship with striatal neuronal dysfunction measured with 11C-raclopride (RAC) PET, and the role of PK PET as a possible marker of subclinical disease progression in PGCs. Eleven HD PGCs underwent PK and RAC PET. Their results were compared with those of healthy controls. PK and RAC binding was measured using region-of-interest analysis. Regional increases in PK binding were also localized with voxel-based statistical parametric mapping. HD PGCs had lower striatal RAC binding than the controls but significantly higher striatal and cortical PK binding. Individual levels of higher striatal PK binding in PGCs correlated with lower striatal RAC binding and, after excluding one outlier, with a higher probability of developing HD in 5 years. The inverse association between striatal PK and RAC binding in PGCs continues into early to moderate stages of HD. This study demonstrated for the first time in vivo widespread microglial activation in preclinical HD which correlated with striatal neuronal dysfunction. These findings indicate that microglial activation is an early event in the pathogenic processes of HD and is associated with subclinical progression of disease. PK PET may be a useful marker of active subclinical disease and a means of investigating the efficacy of neuroprotection strategies in PGCs. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17400599&query_hl=1 ER - TY - JFULL T1 - MRI of moving subjects using multislice snapshot images with volume reconstruction (SVR): application to fetal, neonatal, and adult brain studies. A1 - Jiang, S A1 - Xue, H A1 - Glover, A A1 - Rutherford, M A1 - Rueckert, D A1 - Hajnal, JV J1 - IEEE Trans Med Imaging Y1 - 2007/07// VL - 26 SN - 0278-0062 SP - 967 EP - 980 N2 - Motion degrades magnetic resonance (MR) images and prevents acquisition of self-consistent and high-quality volume images. A novel methodology, Snapshot magnetic resonance imaging (MRI) with Volume Reconstruction (SVR) has been developed for imaging moving subjects at high resolution and high signal-to-noise ratio (SNR). The method combines registered 2-D slices from sequential dynamic single-shot scans. The SVR approach requires that the anatomy in question is not changing shape or size and is moving at a rate that allows snapshot images to be acquired. After imaging the target volume repeatedly to guarantee sufficient sampling every where, a robust slice-to-volume registration method has been implemented that achieves alignment of each slice within 0.3 mm in the examples tested. Multilevel scattered interpolation has been used to obtain high-fidelity reconstruction with root-mean-square (rms) error that is less than the noise level in the images. The SVR method has been performed successfully for brain studies on subjects that cannot stay still, and in some cases were moving substantially during scanning. For example, awake neonates, deliberately moved adults and, especially, on fetuses, for which no conventional high-resolution 3-D method is currently available. Fine structure of the in-utero fetal brain is clearly revealed for the first time and substantial SNR improvement is realized by having many individually acquired slices contribute to each voxel in the reconstructed image. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17649910&query_hl=1 ER - TY - JFULL T1 - Cytotoxic killing and immune evasion by repair A1 - Chan, C A1 - George, AJT A1 - Stark, J J1 - J STAT PHYS Y1 - 2007/07// VL - 128 SN - 0022-4715 SP - 393 EP - 411 N2 - The interaction between the immune system and pathogens is a complex one, with pathogens constantly developing new ways of evading destruction by the immune system. The immune system's task is made even harder when the pathogen in question is an intra-cellular one (such as a virus or certain bacteria) and it is necessary to kill the infected host cell in order to eliminate the pathogen. This causes damage to the host, and such killing therefore needs to be carefully controlled, particularly in tissues with poor regenerative potential, or those involved in the immune response itself. Host cells therefore possess repair mechanisms which can counteract killing by immune cells. These in turn can be subverted by pathogens which up-regulate the resistance of infected cells to killing. In this paper, we explore the hypothesis that this repair process plays an important role in determining the efficacy of evasion and escape from immune control. We model a situation where cytotoxic T lymphocytes (CTL) and natural killer (NK) cells kill pathogen-infected and turnout cells by directed secretion of preformed granules containing perforin and granzymes. Resistance to such killing can be conferred by the expression of serine protease inhibitors (serpins). These are utilized by several vitally infected and tumour cells, as well as playing a role in the protection of host bystander, immune and immune-privileged cells. We build a simple stochastic model of cytotoxic killing, where serpins can neutralize granzymes stoichiometrically by forming an irreversible complex, and the survival of the cell is determined by the balance between serpin depletion and replenishment, which in its simplest form is equivalent to the well known shot noise process. We use existing analytical results for this process, and additional simulations to analyse the effects of repair on cytotoxic killing. We then extend the model to the case of a replicating target cell population, which gives a branching process coupled to shot noise. We show how the process of repair can have a major impact on the dynamics of pathogen evasion and escape of tumour cells from immune surveillance. ER - TY - JFULL T1 - Imaging non-dopaminergic function in Parkinson's disease. A1 - Brooks, DJ J1 - Mol Imaging Biol Y1 - 2007/07// VL - 9 SN - 1536-1632 SP - 217 EP - 222 N2 - In Parkinson's disease (PD), there is degeneration of the cholinergic, noradrenergic, and serotonergic systems in addition to dopaminergic projections. Function of these non-dopaminergic systems can be imaged with positron emission tomography (PET) and single photon emission computed tomography (SPECT) and correlated with motor and nonmotor symptomatology. In addition, neuronal loss in PD is associated with microglial activation. The role of microglia in driving the disease process remains uncertain. This review presents and discusses current findings in these areas. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17340229&query_hl=1 ER - TY - JFULL T1 - Anti-LFA-1 monotherapy prevents neointimal formation in a murine model of transplant intimal hyperplasia. A1 - Soleimani, B A1 - Wieczorek, G A1 - Katopodis, A A1 - Zenke, G A1 - George, AJ A1 - Hornick, PI A1 - Weitz-Schmidt, G J1 - J Heart Lung Transplant Y1 - 2007/07// VL - 26 SN - 1557-3117 SP - 724 EP - 731 N2 - BACKGROUND: Cardiac allograft vasculopathy (CAV) is the pre-eminent cause of late cardiac allograft failure. It is characterized by a concentric intimal hyperplasia, which we designate transplant intimal hyperplasia (TIH). To date, blockade of the adhesion molecule lymphocyte function-associated antigen-1 (LFA-1) has been shown to be effective in preventing TIH in experimental models of transplantation, but only when combined with other immunosuppressants. In this study we explored the impact of monotherapy against LFA-1 in a carotid artery allograft model of TIH. METHODS: B10A(2R) (H-2(h2)) mice were used as donors and C57BL/6 (H-2(b)) mice used as recipients. The recipients were treated with a monoclonal antibody against LFA-1alpha (M17/4) or isotype-matched control immunoglobulin. Grafts were harvested after 35 days and analyzed by histomorphometry and immunohistochemistry. Blood samples were taken and analyzed by differential cell count and alloantibody levels. RESULTS: We found that treatment with M17/4 resulted in a significant reduction in TIH compared with controls. Immunostaining revealed that LFA-1alpha blockade inhibited CD45+ leukocyte infiltration, prevented intimal smooth muscle cell (SMC) proliferation, and preserved the medial SMC population. Finally, we demonstrated a reduction in the serum alloantibody titer in the group treated with anti-LFA-1alpha when compared with controls. CONCLUSIONS: We have demonstrated for the first time that LFA-1alpha blockade on its own can prevent development of TIH in an experimental model. The concept of modulating LFA-1alpha-mediated leukocyte migration and T-cell activation may therefore be of relevance to clinical cardiac transplantation and, as such, represents a potential target for therapeutic intervention against clinical CAV. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17613404&query_hl=1 ER - TY - JFULL T1 - Three-tesla cardiac magnetic resonance imaging for preterm infants. A1 - Foran, AM A1 - Fitzpatrick, JA A1 - Allsop, J A1 - Schmitz, S A1 - Franklin, J A1 - Pamboucas, C A1 - O'Regan, D A1 - Hajnal, JV A1 - Edwards, AD J1 - Pediatrics Y1 - 2007/07// VL - 120 SN - 1098-4275 SP - 78 EP - 83 N2 - OBJECTIVES: We aimed to establish the feasibility of acquiring 3.0-T cardiac MRIs without sedation, anesthesia, or breath-holding for preterm infants and to obtain preliminary quantitative data on left ventricular function in this population. METHODS: Twelve preterm infants underwent 3.0-T cardiac MRI without sedation or breath-holding. The median gestational age was 29 weeks (range: 26-33 weeks), the median birth weight was 1240 g (range: 808-2200 g), and the median postconceptional age at the time of cardiac MRI was 33 weeks (range: 31-40 weeks). Anatomic images were acquired with T2-weighted spin-echo sequences, and ventricular function was assessed with balanced steady-state free precession cine sequences. We assessed left ventricular function by using the area-length ejection fraction method on horizontal long-axis images and the volumetric Sergeant's discs method of analysis on short-axis images. RESULTS: Imaging was successful for 10 of 12 infants. For those 10, the area-length ejection fraction method in the horizontal long-axis plane estimated median stroke volume at 2.9 mL, cardiac output at 0.4 L/minute, end-diastolic volume at 3.8 mL, end-systolic volume at 0.3 mL, and ejection fraction at 74.6%. Short-axis volumetric estimations were made for 4 infants. With this approach, the median stroke volume was 2.4 mL, cardiac output 0.35 L/minute, end-diastolic volume 4.3 mL, end-systolic volume 2.1 mL, and ejection fraction 56%. CONCLUSIONS: Three-tesla cardiac MRI is feasible for preterm infants without sedation, anesthesia, or breath-holding and has the potential to provide a wide range of precise quantitative data that may be of great value for the investigation of cardiac function in preterm infants. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17606564&query_hl=1 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 - Structural linear measurements in the newborn brain: accuracy of cranial ultrasound compared to MRI. A1 - Leijser, LM A1 - Srinivasan, L A1 - Rutherford, MA A1 - Counsell, SJ A1 - Allsop, JM A1 - Cowan, FM J1 - Pediatr Radiol Y1 - 2007/07// VL - 37 SN - 0301-0449 SP - 640 EP - 648 N2 - BACKGROUND: Structural size in the neonatal brain is of clinical importance. Cranial ultrasonography (cUS) is the primary method used for evaluating the neonatal brain and it is important to know whether linear measurements made using this technique are accurate. OBJECTIVE: To compare linear measurements of different cerebral structures made from neonatal cUS and contemporaneous MRI. MATERIALS AND METHODS: Preterm and term infants studies with cUS and MRI on the same day were studied. Linear measurements made using both techniques from many cerebral structures were compared using a paired t-test. RESULTS: A total of 44 sets of scans from 26 preterm and 8 term infants were assessed. Small but significant differences between the cUS and MRI measurements (P<0.05) were found for the ventricular index, the posterior horn depth of the lateral ventricle, the extracerebral space and interhemispheric fissure, and the cortex of the cingulate gyrus. No significant differences were found for any other measurements. CONCLUSION: Linear measurements from cUS are accurate for most neonatal cerebral structures. Significant differences compared to MRI were found for a few structures, but only for the cortex were the absolute differences marked and possibly of clinical importance. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17486330&query_hl=1 ER - TY - JFULL T1 - [(11)C]Flumazenil PET in temporal lobe epilepsy: do we need an arterial input function or kinetic modeling? A1 - Hammers, A A1 - Panagoda, P A1 - Heckemann, RA A1 - Kelsch, W A1 - Turkheimer, FE A1 - Brooks, DJ A1 - Duncan, JS A1 - Koepp, MJ J1 - J Cereb Blood Flow Metab Y1 - 2007/06/20/ SN - 0271-678X N2 - Reduced signal on [(11)C]]flumazenil (FMZ) positron emission tomography (PET) is associated with epileptogenic foci. Linear correlations within individuals between parametric and nonparametric images of FMZ binding have been shown, and various methods have been used, without comparison of diagnostic usefulness. Using hippocampal sclerosis (HS) as a test case, we formally compare the diagnostic yield of parametric images obtained either with a parent tracer arterial plasma input function and spectral analysis (yielding volume-of-distribution (VD) images), or with an image-based input function and the simplified reference tissue model (binding potential images, BP-SRTM) with the diagnostic yield of semiquantitative-integrated (ADD) images from 10 to 20 or 20 to 40 mins (ADD1020 and ADD2040). Dynamic 90-min [(11)C]FMZ PET datasets and arterial plasma input functions were available for 15 patients with medically refractory medial temporal lobe epilepsy (TLE) and histologically verified unilateral HS and for 13 control subjects. SPM2 was used for analysis. ADD1020 and ADD2040 images showed decreased FMZ uptake ipsilateral to the epileptogenic hippocampus in 13/15 cases; 6/13 had bilateral decreases in the ADD1020 analysis and 5/13 in the ADD2040 analysis. BP-SRTM images detected ipsilateral decreases in 12/15 cases, with bilateral decreases in three. In contrast, VD images showed ipsilateral hippocampal decreases in all 15 patients, with bilateral decreases in three patients. Bilateral decreases in the ADD images tended to be more symmetrical and in one case were more marked contralaterally. Full quantification with an image-independent input should ideally be used in the evaluation of FMZ PET; at least in TLE, intrasubject correlations do not predict equivalent clinical usefulness.Journal of Cerebral Blood Flow & Metabolism advance online publication, 20 June 2007; doi:10.1038/sj.jcbfm.9600515. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17579659&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 - STN stimulation alters pallidal-frontal coupling during response selection under competition A1 - Thobois, S A1 - Hotton, GR A1 - Pinto, S A1 - Wilkinson, L A1 - Limousin-Dowsey, P A1 - Brooks, DJ A1 - Jahanshahi, M J1 - J CEREBR BLOOD F MET Y1 - 2007/06// VL - 27 SN - 0271-678X SP - 1173 EP - 1184 N2 - To investigate the effects of bilateral subthalamic nucleus (STN) stimulation on patterns of brain activation during random number generation (RNG), a task that requires suppression of habitual counting and response selection under competition. We used (H2O)-O-15 positron emission tomography to investigate the changes of regional cerebral blood flow (rCBF) induced by bilateral STN stimulation during a RNG task, in six patients with Parkinson's disease. Paced RNG at 1Hz was compared with a control counting task. Both tasks were performed off medication with deep brain stimulation on and off. Subthalamic nucleus stimulation had a negative effect on performance of fast-paced RNG, leading to reduced randomness and increased habitual counting. Subthalamic nucleus stimulation also induced a reduction of rCBF in the left dorsal frontal gyrus, inferior frontal gyrus, dorsolateral prefrontal cortex, posterior and right anterior cingulate, and an increase of rCBF in the right internal globus pallidum (GPi) during RNG. Stimulation of the STN significantly altered pallidal coupling with frontal and temporal areas compared with when the stimulators were off. In conclusion, during RNG: (i) STN stimulation activates its output neurons to the GPi; (ii) STN stimulation induces increased inhibition of a prefrontal-cingulate network. This is the first direct evidence that STN stimulation significantly alters pallidal coupling with prefrontal, cingulate, and temporal cortices during performance of a task that requires response selection under competition. ER - TY - JFULL T1 - Enhanced activation of reward mediating prefrontal regions in response to food stimuli in Prader-Willi syndrome. A1 - Miller, JL A1 - James, GA A1 - Goldstone, AP A1 - Couch, JA A1 - He, G A1 - Driscoll, DJ A1 - Liu, Y J1 - J Neurol Neurosurg Psychiatry Y1 - 2007/06// VL - 78 SN - 1468-330X SP - 615 EP - 619 N2 - BACKGROUND: Individuals with Prader-Willi syndrome (PWS) exhibit severe disturbances in appetite regulation, including delayed meal termination, early return of hunger after a meal, seeking and hoarding food and eating of non-food substances. Brain pathways involved in the control of appetite in humans are thought to include the hypothalamus, frontal cortex (including the orbitofrontal, ventromedial prefrontal, dorsolateral prefrontal and anterior cingulate areas), insula, and limbic and paralimbic areas. We hypothesised that the abnormal appetite in PWS results from aberrant reward processing of food stimuli in these neural pathways. METHODS: We compared functional MRI blood oxygen level dependent (BOLD) responses while viewing pictures of food in eight adults with PWS and eight normal weight adults after ingestion of an oral glucose load. RESULTS: Subjects with PWS demonstrated significantly greater BOLD activation in the ventromedial prefrontal cortex than controls when viewing food pictures. No significant differences were found in serum insulin, glucose or triglyceride levels between the groups at the time of the scan. CONCLUSIONS: Individuals with PWS had an increased BOLD response in the ventromedial prefrontal cortex compared with normal weight controls when viewing pictures of food after an oral glucose load. These findings suggest that an increased reward value for food may underlie the excessive hunger in PWS, and support the significance of the frontal cortex in modulating the response to food in humans. Our findings in the extreme appetite phenotype of PWS support the importance of the neural pathways that guide reward related behaviour in modulating the response to food in humans. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17158560&query_hl=1 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 - 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 - A multivariate statistical analysis of the developing human brain in preterm infants A1 - Thomaz, CE A1 - Boardman, JP A1 - Counsell, S A1 - Hill, DLG A1 - Hajnal, JV A1 - Edwards, AD A1 - Rutherford, MA A1 - Gillies, DF A1 - Rueckert, D J1 - IMAGE VISION COMPUT Y1 - 2007/06/01/ VL - 25 SN - 0262-8856 SP - 981 EP - 994 N2 - Preterm delivery accounts for 5% of all deliveries and its consequences contribute to significant individual, medical, and social problems. The neuroanatomical substrates of these disorders are not known, but are essential for understanding mechanisms of causation, and developing strategies for intervention. In the recent years, multivariate pattern recognition methods that analyse all voxels simultaneously have been proposed to characterise the neuroanatomical differences between a reference group of magnetic resonance (MR) images and the population under investigation. Most of these techniques have overcome the difficulty of dealing with the inherent high dimensionality of 3D MR brain image data by using pre-processed segmented images or a small number of specific features. However, an intuitive way of mapping the classification results back into the original image domain for further interpretation remains challenging. In this paper, we propose the idea of using Principal Components Analysis (PCA) plus the maximum uncertainty Linear Discriminant Analysis (MLDA) approach to classify and analyse MR brain images that have been aligned with either affine or non-rigid registration techniques. This approach avoids the computation costs intrinsic to commonly used covariance-based optimisation processes for solving small sample size problems, resulting in a simple and efficient implementation for the maximisation and interpretation of the Fisher's classification results. In order to demonstrate the effectiveness of the approach, we have used a neonatal MR brain data set that contains images of 93 preterm infants at term equivalent age and 20 term controls. Our results indicate that the two-stage linear framework makes clear the statistical differences between the control and preterm samples, showing a classification accuracy of 95.0% and 97.8% for the controls and preterms samples, respectively, using the leave-one-out method. Moreover, it provides a simple and intuitive method of visually analysing the differences between preterm infants at term equivalent age and the control group, such as differences in cerebrospinal fluid spaces, structure of the corpus callosum, and subtle differences in myelination. (C) 2006 Elsevier B.V. All rights reserved. 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 - 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 - 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 - An evaluation of the feasibility, validity, and reliability of laparoscopic skills assessment in the operating room. A1 - Aggarwal, R A1 - Grantcharov, T A1 - Moorthy, K A1 - Milland, T A1 - Papasavas, P A1 - Dosis, A A1 - Bello, F A1 - Darzi, A J1 - Ann Surg Y1 - 2007/06// VL - 245 SN - 0003-4932 SP - 992 EP - 999 N2 - OBJECTIVE: To assess the use of a synchronized video-based motion tracking device for objective, instant, and automated assessment of laparoscopic skill in the operating room. SUMMARY BACKGROUND DATA: The assessment of technical skills is fundamental to recognition of proficient surgical practice. It is necessary to demonstrate the validity, reliability, and feasibility of any tool to be applied for objective measurement of performance. METHODS: Nineteen subjects, divided into 13 experienced (performed >100 laparoscopic cholecystectomies) and 6 inexperienced (performed <10 LCs) surgeons completed LCs on 53 patients who all had a diagnosis of biliary colic. Each procedure was recorded with the ROVIMAS video-based motion tracking device to provide an objective measure of the surgeon's dexterity. Each video was also rated by 2 experienced observers on a previously validated operative assessment scale. RESULTS: There were significant differences for motion tracking parameters between the 2 groups of surgeons for the Calot triangle dissection part of procedure for time taken (P = 0.002), total path length (P = 0.026), and number of movements (P = 0.005). Both motion tracking and video-based assessment displayed intertest reliability, and there were good correlations between the 2 modes of assessment (r = 0.4 to 0.7, P < 0.01). CONCLUSIONS: An instant, objective, valid, and reliable mode of assessment of laparoscopic performance in the operating room has been defined. This may serve to reduce the time taken for technical skills assessment, and subsequently lead to accurate and efficient audit and credentialing of surgeons for independent practice. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17522527&query_hl=1 ER - TY - JFULL T1 - Early assessment of visual function in full term newborns. A1 - Ricci, D A1 - Cesarini, L A1 - Groppo, M A1 - De Carli, A A1 - Gallini, F A1 - Serrao, F A1 - Fumagalli, M A1 - Cowan, F A1 - Ramenghi, LA A1 - Anker, S A1 - Mercuri, E A1 - Mosca, F J1 - Early Hum Dev Y1 - 2007/05/18/ SN - 0378-3782 N2 - BACKGROUND:: The assessment of visual function is part of all the neonatal neurological examination but it is often limited to the evaluation of ocular movements and the ability to fix and follow a target. AIM OF THE STUDY:: To develop a simple battery of test items assessing different aspects of visual function that could be used as early as 48 h after birth. STUDY DESIGN AND SUBJECTS:: The final battery, which has been used in 50 full term low risk neonates, includes 9 items assessing ocular motility, both spontaneous and with focus on a visual target, fixation and tracking (horizontal, vertical and in an arc), the ability to discriminate stripes of different spatial frequency, and attention at distance. RESULTS:: The battery proved easy to perform and did not require long training. The testing did not require a specific setting and was easy to use even for infants in incubators. The equipment is small and cleanable. CONCLUSION:: Our paper suggests that a simple battery, which can be performed in 5/10 min, can be easily applied and provides useful information on various aspects of early neonatal visual function. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17513071&query_hl=1 ER - TY - JFULL T1 - A systematic comparison of kinetic modelling methods generating parametric maps for [(11)C]-(R)-PK11195. A1 - Anderson, AN A1 - Pavese, N A1 - Edison, P A1 - Tai, YF A1 - Hammers, A A1 - Gerhard, A A1 - Brooks, DJ A1 - Turkheimer, FE J1 - Neuroimage Y1 - 2007/05/15/ VL - 36 SN - 1053-8119 SP - 28 EP - 37 N2 - [(11)C]-(R)-PK11195 is presently the most widely used radiotracer for the monitoring of microglia activity in the central nervous system (CNS). Microglia, the resident immune cells of the brain, play a critical role in acute and chronic diseases of the central nervous system and in host defence against neoplasia. The purpose of this investigation was to evaluate the reliability and sensitivity of five kinetic modelling methods for the formation of parametric maps from dynamic [(11)C]-(R)-PK11195 studies. The methods we tested were the simplified reference tissue model (SRTM), basis pursuit, a simple target-to-reference ratio, the Logan plot and a wavelet based Logan plot. For the reliability assessment, the test-retest data consisted of four Alzheimer's patients that were scanned twice at approximately a six-week interval. For the sensitivity assessment, comparison of [(11)C]-(R)-PK11195 binding in Huntington's disease (HD) patients and normal subjects was performed using a group contrast to localize significant increases in mean pixel volume of distribution (VD) in HD. In all instances, a reference region kinetic extracted by a supervised clustering technique was used as input function. Reliability was assessed by use of the intra-class correlation coefficient (ICC) across a wide set of anatomical regions and it was found that the wavelet-based Logan plot, basis pursuit and SRTM gave the highest ICC values on average. The same methods produced the highest z-scores resulting from increases in mean striatal VD in HD patients compared with controls. The reference-to-target ratio and the Logan graphical approach were significantly less reliable and less sensitive. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17398120&query_hl=1 ER - TY - JFULL T1 - Creatine supplements in patients with idiopathic inflammatory myopathies who are clinically weak after conventional pharmacologic treatment: Six-month, double-blind, randomized, placebo-controlled trial. A1 - Chung, YL A1 - Alexanderson, H A1 - Pipitone, N A1 - Morrison, C A1 - Dastmalchi, M A1 - Ståhl-Hallengren, C A1 - Richards, S A1 - Thomas, EL A1 - Hamilton, G A1 - Bell, JD A1 - Lundberg, IE A1 - Scott, DL J1 - Arthritis Rheum Y1 - 2007/05/15/ VL - 57 SN - 0004-3591 SP - 694 EP - 702 N2 - OBJECTIVE: To test the hypothesis that oral creatine supplements with exercise are more effective than exercise alone in improving muscle function in patients with established dermatomyositis or polymyositis receiving chronic medical therapies who are clinically weak yet stable. METHODS: In a 6-month, 2-center, double-blind, randomized controlled trial, patients were randomized to receive oral creatine supplements (8 days, 20 gm/day then 3 gm/day) or placebo. All patients followed a home exercise program. The primary outcome was aggregate functional performance time (AFPT), reflecting the ability to undertake high-intensity exercise. Secondary outcomes included a functional index measuring endurance and muscle bioenergetics on (31)P magnetic resonance spectroscopy ((31)P MRS). Patients were receiving stable immunosuppressive treatment and/or corticosteroids. RESULTS: A total of 37 patients with polymyositis or dermatomyositis were randomized (19 to creatine, 18 to placebo); 29 completed 6 months. Intent-to-treat analyses demonstrated that AFPT improved significantly at 6 months with creatine (median decrease 13%, range -32-8%) compared with placebo (median decrease 3%, range -13-16%; P = 0.029 by Mann-Whitney U test). A completer analysis also showed significant benefits from creatine (P = 0.014). The functional index improved significantly with both creatine and placebo (P < 0.05 by paired Wilcoxon's rank sum test), with a significant benefit between groups in the completer analysis only. Phosphocreatine/beta-nucleoside triphosphate ratios using MRS increased significantly in the creatine group (P < 0.05) but not in the control group. No clinically relevant adverse events were associated with creatine. CONCLUSION: Oral creatine supplements combined with home exercises improve functional performance without significant adverse effects in patients with polymyositis or dermatomyositis. They appear safe, effective, and inexpensive. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17471547&query_hl=1 ER - TY - JFULL T1 - Automatic detection and quantification of hippocampal atrophy on MRI in temporal lobe epilepsy: a proof-of-principle study. A1 - Hammers, A A1 - Heckemann, R A1 - Koepp, MJ A1 - Duncan, JS A1 - Hajnal, JV A1 - Rueckert, D A1 - Aljabar, P J1 - Neuroimage Y1 - 2007/05/15/ VL - 36 SN - 1053-8119 SP - 38 EP - 47 N2 - In temporal lobe epilepsy (TLE), hippocampal atrophy (HA) is a marker of poor prognosis regarding seizure remission, but predicts success of anterior temporal lobe resection. Manual quantification of HA on MRI is time-consuming and limited by investigator availability. Normal ranges of hippocampal volumes, both in absolute terms and relative to intracranial volume, and of hippocampal asymmetry were defined using an automatic label propagation and decision fusion technique based on thirty manually derived atlases of healthy controls. Manual test-retest reliability and overlaps of automatically and manually determined hippocampal volumes were quantified with similarity indices (SIs). Correct clinical identification of ipsilateral HA, and contralaterally normal hippocampal volumes, was determined in nine patients with histologically confirmed hippocampal sclerosis in terms of volumes and asymmetry indices (AIs) for standard statistical thresholds and with receiver operating characteristic (ROC) analysis. Manual test-retest reliability was very high, with SIs between 0.87 and 0.90. Manual and automatic hippocampus labels overlapped with a SI of 0.83 on the unaffected but with 0.76 on the atrophic side. Accuracy was higher for less atrophic hippocampi. The automatic method correctly identified 6/9 HAs in terms of absolute volume, 7/9 in terms of relative volume at a standard 2 SD threshold, and 9/9 for AIs. ROC-determined thresholds allowed clinically desirable correct identification of all HAs (100% sensitivity) with 85-100% specificity for volumes, and 100% specificity for AIs. The method has the potential to automatically detect unilateral HA, but further work is needed to determine its performance in detecting clinically important bilateral disease. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17428687&query_hl=1 ER - TY - JFULL T1 - Pioglitazone added to conventional lipid-lowering treatment in familial combined hyperlipidaemia improves parameters of metabolic control: Relation to liver, muscle and regional body fat content. A1 - Thomas, EL A1 - Potter, E A1 - Tosi, I A1 - Fitzpatrick, J A1 - Hamilton, G A1 - Amber, V A1 - Hughes, R A1 - North, C A1 - Holvoet, P A1 - Seed, M A1 - Betteridge, DJ A1 - Bell, JD A1 - Naoumova, RP J1 - Atherosclerosis Y1 - 2007/05/04/ SN - 0021-9150 N2 - Familial combined hyperlipidaemia (FCHL) is a complex genetic disorder conferring high risk of premature atherosclerosis, characterized by high cholesterol and/or triglyceride, low high density lipoprotein (HDL) cholesterol and insulin resistance. We examined whether pioglitazone, added to conventional lipid-lowering therapy, would favourably affect metabolic parameters and alter body fat content. We undertook a randomized, double blind, placebo-controlled study in 22 male patients with FCHL treated with pioglitazone or matching placebo 30mg daily for 4 weeks, increasing to 45mg for 12 weeks. Magnetic resonance imaging and proton magnetic resonance spectroscopy were performed to measure adipose tissue (AT) body content as well as intrahepatocellular lipids (IHCL) and intramyocellular lipids (IMCL) at baseline and after treatment. Significantly improved in the pioglitazone group were: triglyceride/HDL (atherogenic index of plasma) -32.3% (p=0.002), plasma glucose -4.4% (p=0.03), alanine-aminotransferase (ALT) -7.7% (p=0.005) and adiponectin 130.1% (p=0.001). Pioglitazone treatment resulted in a significant increase in total (5.3%, p=0.02) and subcutaneous (7.1%, p=0.003) adipose tissue as well as in soleus-IMCL levels (47.4%, p=0.02) without alteration in intra-abdominal AT or IHCL. Changes in ALT and AST and IHCL were strongly correlated (r=0.72, p<0.01; r=.0.86, p<0.01, respectively). In patients with FCHL on conventional lipid-lowering therapy, the addition of pioglitazone acts favourably on several metabolic parameters. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17482623&query_hl=1 ER - TY - JFULL T1 - Reconstruction of undersampled dynamic images by modeling the motion of object elements. A1 - Prieto, C A1 - Batchelor, PG A1 - Hill, DL A1 - Hajnal, JV A1 - Guarini, M A1 - Irarrazaval, P J1 - Magn Reson Med Y1 - 2007/05// VL - 57 SN - 0740-3194 SP - 939 EP - 949 N2 - Dynamic MRI is restricted due to the time required to obtain enough data to reconstruct the image sequence. Several undersampled reconstruction techniques have been proposed to reduce the acquisition time. In most of these techniques the nonacquired data are recovered by modeling the temporal information as varying pixel intensities represented in time or in temporal frequencies. Here we propose a new approach that recovers the missing data through a motion estimation of the object elements ("obels," or pieces of tissue) of the image. This method assumes that an obel displacement through the sequence has lower bandwidth than fluctuations in pixel intensities caused by the motion, and thus it can be modeled with fewer parameters. Preliminary results show that this technique can effectively reconstruct (with root mean square (RMS) errors below 4%) cardiac images and joints with undersampling factors of 8 and 4, respectively. Moreover, in the reconstruction process an approximation of the motion vectors is obtained for each obel, which can be used to quantify dynamic information. In this method the motion need not be confined to a part of the field of view (FOV) or to a portion of the temporal frequency. It is appropriate for dynamic studies in which the obels' motion model has fewer parameters than the number of acquired samples. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17457881&query_hl=1 ER - TY - JFULL T1 - Determinants of outcomes after head cooling for neonatal encephalopathy. A1 - Wyatt, JS A1 - Gluckman, PD A1 - Liu, PY A1 - Azzopardi, D A1 - Ballard, R A1 - Edwards, AD A1 - Ferriero, DM A1 - Polin, RA A1 - Robertson, CM A1 - Thoresen, M A1 - Whitelaw, A A1 - Gunn, AJ A1 - CoolCap Study Group J1 - Pediatrics Y1 - 2007/05// VL - 119 SN - 1098-4275 SP - 912 EP - 921 N2 - OBJECTIVE: The goal of this study was to evaluate the role of factors that may determine the efficacy of treatment with delayed head cooling and mild systemic hypothermia for neonatal encephalopathy. METHODS: A total of 218 term infants with moderate to severe neonatal encephalopathy plus abnormal amplitude-integrated electroencephalographic recordings, assigned randomly to head cooling for 72 hours, starting within 6 hours after birth (with the rectal temperature maintained at 34.5 +/- 0.5 degrees C), or conventional care, were studied. Death or severe disability at 18 months of age was assessed in a multicenter, randomized, controlled study (the CoolCap trial). RESULTS: Treatment, lower encephalopathy grade, lower birth weight, greater amplitude-integrated electroencephalographic amplitude, absence of seizures, and higher Apgar score, but not gender or gestational age, were associated significantly with better outcomes. In a multivariate analysis, each of the individually predictive factors except for Apgar score remained predictive. There was a significant interaction between treatment and birth weight, categorized as > or =25th or <25th percentile for term, such that larger infants showed a lower frequency of favorable outcomes in the control group but greater improvement with cooling. For larger infants, the number needed to treat was 3.8. Pyrexia (> or =38 degrees C) in control infants was associated with adverse outcomes. Although there was a small correlation with birth weight, the adverse effect of greater birth weight in control infants remained significant after adjustment for pyrexia and severity of encephalopathy. CONCLUSIONS: Outcomes after hypothermic treatment were strongly influenced by the severity of neonatal encephalopathy. The protective effect of hypothermia was greater in larger infants. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17473091&query_hl=1 ER - TY - JFULL T1 - Deletion of the c-Jun N-terminal kinase 3 gene protects neonatal mice against cerebral hypoxic-ischaemic injury. A1 - Pirianov, G A1 - Brywe, KG A1 - Mallard, C A1 - Edwards, AD A1 - Flavell, RA A1 - Hagberg, H A1 - Mehmet, H J1 - J Cereb Blood Flow Metab Y1 - 2007/05// VL - 27 SN - 0271-678X SP - 1022 EP - 1032 N2 - c-Jun N-terminal kinase 3 (JNK3) is a member of the stress-activated group of mitogen-activated protein kinases. c-Jun N-terminal kinase 3 is a potent mediator of apoptosis and the use of JNK inhibitors or jnk3 gene deletion each protect against brain injury in adults. However, little is known about the role of JNK3 or its mechanism of action in neonatal brain injury. The aim of the present study was to compare the vulnerability of neonatal JNK3 knockout (JNK3 KO) mice and wild-type (WT) mice to cerebral hypoxic-ischaemic injury (HII) using unilateral-carotid occlusion combined with transient hypoxia. The degree of neural tissue loss in JNK3 KO mice was substantially reduced compared with WT mice (JNK3 KO 27.8%+/-2.8% versus WT 48.3%+/-2.0%, P 72 h after the last training session. Liver and skeletal muscle triacylglycerol content was measured by magnetic resonance spectroscopy and visceral adipose tissue by cross-sectional computer tomography scanning.After 6 weeks, fasting glycerol, palmitic acid Ra (p=0.003, p=0.042) and NEFA concentration (p=0.005) were decreased in the exercise group with no change in the control group. The effects of low-dose insulin on EGP and of high-dose insulin on glucose uptake and metabolic clearance rate were enhanced in the exercise group but not in the control group (p=0.026; p=0.007 and p=0.04). There was no change in muscle triacylglycerol and liver fat in either group.Decreased availability of circulating NEFA may contribute to the observed improvement in the insulin sensitivity of EGP and glucose uptake following 6 weeks of moderate exercise. ER - TY - JFULL T1 - CMR of ventricular function. A1 - Keenan, NG A1 - Pennell, DJ J1 - Echocardiography Y1 - 2007/02// VL - 24 SN - 0742-2822 SP - 185 EP - 193 N2 - Cardiovascular magnetic resonance (CMR) is the reference standard for the assessment of ventricular dimensions, function, and mass in terms of accuracy and reproducibility. It has been thoroughly validated both ex vivo and against other imaging techniques. Measurements are highly accurate and no geometrical assumptions need to be made about the ventricle. A routine ventricular dataset of images can be acquired in less than 5 minutes and analyzed in about the same time. The field is rapidly advancing with increasing automation and simplification in both image acquisition and analysis. Using parallel and real time imaging techniques, good quality data can be obtained even in patients who are unable to hold their breath. While providing useful information in all patients with suspected heart failure, CMR should particularly be considered in those with poor echo windows, where it can also be combined with myocardial stress. Tagging techniques can provide highly detailed information about myocardial torsion and strain for individual myocardial segments. In a research environment, the very high degree of interscan reproducibility can dramatically reduce the number of patients needed to perform clinical trials. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17313554&query_hl=1 ER - TY - JFULL T1 - An Indian kindred with reversible dystonia and parkinsonism A1 - Khan, NL A1 - Bhatt, M A1 - Brooks, DJ A1 - Korlipara, P A1 - Schapira, A A1 - Piccini, P A1 - Wood, NW A1 - Bhatia, K J1 - J NEUROL NEUROSUR PS Y1 - 2007/02// VL - 78 SN - 0022-3050 SP - 210 EP - 210 ER - TY - JFULL T1 - Motion tracking systems for assessment of surgical skill. A1 - Aggarwal, R A1 - Dosis, A A1 - Bello, F A1 - Darzi, A J1 - Surg Endosc Y1 - 2007/02// VL - 21 SN - 1432-2218 SP - 339 EP - 339 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17146598&query_hl=1 ER - TY - JFULL T1 - Lack of influence of mild hypothermia on amplitude integrated-electroencephalography in neonates receiving extracorporeal membrane oxygenation. A1 - Horan, M A1 - Azzopardi, D A1 - Edwards, AD A1 - Firmin, RK A1 - Field, D J1 - Early Hum Dev Y1 - 2007/02// VL - 83 SN - 0378-3782 SP - 69 EP - 75 N2 - OBJECTIVE: To observe amplitude integrated electroencephalography (aEEG) in neonates receiving ECMO and to determine whether mild hypothermia influenced the aEEG recording. METHODS: Twenty-six consecutive neonates enrolled in a pilot study of mild hypothermia during ECMO were studied. The first group (N=6) was maintained at 37 degrees C throughout the study period. Subsequent groups were cooled to 36 degrees C (N=4), 35 degrees C (N=5), and finally 34 degrees C (N=6) respectively for 24 h and the final group (N=5) to 34 degrees C for 48 h before being rewarmed to 37 degrees C. The aEEG was recorded continuously during the first 5 days of ECMO. The aEEG was classified as normal, moderately or severely suppressed and examined for the occurrence of seizures. To assess the effect of temperature, the aEEG was compared over 12 h during the final 6 h of cooling and during the first 6 h once infants were rewarmed. RESULTS: No change in aEEG amplitude was noted over the temperature range studied. Of the 26 traces obtained, 16 (62%) were normal throughout, 6 (23%) were intermittently moderately abnormal and 1 (14%) was severely abnormal. Three (11%) traces had periods of frequent seizure activity and these were not associated with clinical manifestations in two neonates. In one infant who suffered a cerebral haemorrhage, the aEEG became abnormal before cranial ultrasound abnormalities were apparent. CONCLUSIONS: Continuous cerebral monitoring with aEEG is feasible during ECMO and may add information to clinical examination. Mild hypothermia to 34 degrees C for up to 48 h does not influence the aEEG suggesting that cerebral monitoring with aEEG is possible during mild hypothermia. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16814962&query_hl=1 ER - TY - JFULL T1 - A Comparison Framework for Breathing Motion Estimation Methods from 4D Imaging A1 - Sarrut, D A1 - Delhay, B A1 - Villard, PF A1 - Boldea, V A1 - Beuve, M A1 - Clarisse, P J1 - Transactions on Medical Imaging Y1 - 2007/// ER - TY - JFULL T1 - Telemedicine in pediatric and perinatal cardiology: Economic evaluation of a service in English hospitals A1 - Dowie, R A1 - Mistry, H A1 - Young, TA A1 - Weatherburn, GC A1 - Gardiner, HM A1 - Rigby, M A1 - Rowlinson, GV A1 - Franklin, RCG J1 - INT J TECHNOL ASSESS Y1 - 2007/// VL - 23 SN - 0266-4623 SP - 116 EP - 125 N2 - Objectives: Pediatric cardiology has an expanding role in fetal and pediatric screening. The aims of this study were to observe how district hospitals use a pediatric telecardiology service, and to compare the costs and outcomes of patients referred to specialists by means of this service or conventionallyMethods: A telemedicine service was set up between a pediatric cardiac center in London and four district hospitals for referrals of second trimester women, newborn babies, and older children. Clinicians in each hospital decided on the role for their service. Clinical events were audited prospectively and costed, and patient surveys were conducted.Results: The hospitals differed in their selection of patient groups for the service. In all, 117 telemedicine patients were compared with 387 patients seen in London or in outreach clinics. Patients selected for telemedicine were generally healthier. For all patients, the mean cost for the initial consultation was 411 pound for tele-referrals and 277 pound for conventional referrals, a nonsignificant difference. Teleconsultations for women and children were significantly more expensive because of technology costs, whereas for babies, ambulance transfers were much more costly. After 6-months follow-up, the difference between referral methods for all patients was nonsignificant (telemedicine, 3,350; pound conventional referrals, 2,172) pound, and nonsignificant within the patient groups.Conclusions: Telemedicine was perceived by cardiologists, district clinicians, and families as reliable and efficient. The equivocal 6-month cost results indicate that investment in the technology is warranted to enhance pediatric and perinatal cardiology services. ER - TY - JFULL T1 - Statistical neuroanatomy of the human inferior frontal gyrus and probabilistic atlas in a standard stereotaxic space. A1 - Hammers, A A1 - Chen, CH A1 - Lemieux, L A1 - Allom, R A1 - Vossos, S A1 - Free, SL A1 - Myers, R A1 - Brooks, DJ A1 - Duncan, JS A1 - Koepp, MJ J1 - Hum Brain Mapp Y1 - 2007/01// VL - 28 SN - 1065-9471 SP - 34 EP - 48 N2 - We manually defined the inferior frontal gyrus (IFG) on high-resolution MRIs in native space in 30 healthy subjects (15 female, median age 31 years; 15 male, median age 30 years), resulting in 30 individual atlases. Using standard software (SPM99), these were spatially transformed to a widely used stereotaxic space (MNI/ICBM 152) to create probabilistic maps. In native space, the total IFG volume was on average 5%, and the gray matter (GM) portion 12% larger in women (not significant). Expressed as a percentage of ipsilateral frontal lobe volume (i.e., correcting for brain size), the IFG was an average of 20%, and the GM portion of the IFG 27%, larger in women (P < 0.005). Correcting for total lobar volume yielded the same result. No asymmetry was found in IFG volumes. There were significant positional differences between the right and left IFGs, with the right IFG being further lateral in both native and stereotaxic space. Variability was similar on the left and right, but more pronounced anteriorly and superiorly. We show differences in IFG volume, composition, and position between sexes and between hemispheres. Applications include probabilistic determination of location in group studies, automatic labeling of new scans, and detection of anatomical abnormalities in patients. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16671082&query_hl=1 ER - TY - JFULL T1 - Non-invasive imaging in adult congenital heart disease using cardiovascular magnetic resonance. A1 - Babu-Narayan, SV A1 - Gatzoulis, MA A1 - Kilner, PJ J1 - J Cardiovasc Med (Hagerstown) Y1 - 2007/01// VL - 8 SN - 1558-2027 SP - 23 EP - 29 N2 - The population of adults with congenital heart disease is growing. Cardiovascular magnetic resonance can provide functional as well as structural data even in the setting of complex anatomy. Due to the lack of ionizing radiation cardiovascular magnetic resonance lends itself to serial follow-up of patients with adult congenital heart disease and can be used for the investigation of altered symptoms or signs, planning of transcatheter or surgical intervention, and for baseline post-operative assessment. Both in clinical practice and in research, cardiovascular magnetic resonance has distinct advantages for assessment of the right as well as left ventricle, as no geometrical assumptions are made, and it can quantify ventricular volumes, function and mass. The utility of cardiovascular magnetic resonance and its potential lifelong contribution to the management of different adult congenital heart disease patients is discussed below. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17255812&query_hl=1 ER - TY - JFULL T1 - Development and evaluation of a virtual intensive therapy unit - VITU. A1 - Theodoropoulos, A A1 - Kneebone, R A1 - Dornan, B A1 - Leonard, R A1 - Bello, F J1 - Stud Health Technol Inform Y1 - 2007/// VL - 125 SN - 0926-9630 SP - 467 EP - 469 N2 - Complex and safety critical healthcare environments like the Intensive Therapy Unit demand highly skilled professionals efficiently interacting with their technologically advanced surroundings and with each other. The ITU environment is daunting to newcomers and contains considerable potential for harm by inexpert treatment. In spite of this, current training is largely workplace based and depends upon observation and supervised practice with real patients. We propose the development of a distributed collaborative environment that recreates key elements of critical care. Centred on a 'virtual bedspace', team members will care for the patient in a way that accurately reflects actual practice and therefore minimises any learning gap. Graded exposure to increasing levels of complexity will ensure that collaborative learning takes place alongside each participant's clinical experience and complements it appropriately. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17377328&query_hl=1 ER - TY - JFULL T1 - Maturation of cerebral electrical activity and development of cortical folding in young very preterm infants. A1 - Biagioni, E A1 - Frisone, MF A1 - Laroche, S A1 - Kapetanakis, BA A1 - Ricci, D A1 - Adeyi-Obe, M A1 - Lewis, H A1 - Kennea, N A1 - Cioni, G A1 - Cowan, F A1 - Rutherford, M A1 - Azzopardi, D A1 - Mercuri, E J1 - Clin Neurophysiol Y1 - 2007/01// VL - 118 SN - 1388-2457 SP - 53 EP - 59 N2 - OBJECTIVE: The aim of this study was to examine the relationship between cortical development and cerebral electrical activity at early gestational ages. METHODS: We obtained EEGs (7.2+/-3.8 days) and MR brain images (3.2+/-2.9 days) after birth in 17<30 week gestation infants without evidence of focal brain injury The EEGs were assessed for discontinuity and characteristic maturational features (delta brush, occipital and temporal sawtooth); cortical development was quantified from MR scans using a specially designed computer programme to measure cortical folding. RESULTS: The inter-burst interval shortened and cortical folding increased with increasing post-menstrual age (PMA). In contrast, the minimum duration of bursts was independent of PMA and cortical folding. Delta brush (8-20 Hz activities) was seen at all PMAs; temporal and occipital sawtooth activities were always more prominent than delta brush but were seen less frequently with increasing PMA and complexity of cortical folding. CONCLUSION: There was a positive correlation between some but not all maturational features of the preterm neonatal EEG and the complexity of whole brain cortical folding and PMA. These relationships were strong for the inter-burst interval, a global measure of maturation, but not strongly seen for regional features such as occipital and temporal sawtooth within this gestational age range. SIGNIFICANCE: Combining neurophysiological examination with detailed neuroimaging gives insights into developmental changes occurring in the very preterm brains and suggests further comparative studies focusing on measures of focal brain development at different gestational ages. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17095296&query_hl=1 ER - TY - JFULL T1 - Mechanical role of pleura on lung motion during breathing A1 - Didier, AL A1 - Villard, PF A1 - Beuve, M A1 - Shariat, B J1 - Computer Methods in Biomechanics and Biomechanical Engineering Y1 - 2007/// ER - TY - JFULL T1 - Cardiovascular magnetic resonance at 0.5T in five patients with permanent pacemakers. A1 - Heatlie, G A1 - Pennell, DJ J1 - J Cardiovasc Magn Reson Y1 - 2007/// VL - 9 SN - 1097-6647 SP - 15 EP - 19 N2 - BACKGROUND: Cardiovascular magnetic resonance (CMR) yields important clinical information which often cannot be obtained from other imaging modalities. Cardiac pacemakers have conventionally been considered a contraindication to CMR, and relatively few data exist on CMR in such patients. METHODS AND RESULTS: We present 5 patients who underwent 6 CMR scans in a 0.5 Tesla scanner. The patients were non-pacemaker dependent, and the pacemakers were reprogrammed prior to scanning to have sub-threshold output. Spin echo, gradient echo and real-time sequences were used with specific absorption rates of up to 0.1 W/kg. A cardiologist was present during each scan, and the patient had continuous electrocardiographic and non-invasive monitoring of vital signs. Five of the scans were carried out without incident providing useful diagnostic information, which was not compromised by obvious artifact from the pacemaker box. In one case, the pacemaker began pacing at maximum voltage at a fixed rate of 100. This patient was removed from the magnet, and there were no clinical sequelae. The mean pre-and post-scan ventricular lead voltage threshold was the same (2.28 V vs 2.28 V). CONCLUSION: Our experience is that CMR at 0.5T in non-pacemaker dependent patents can be performed in closely supervised circumstances where the benefit-risk assessment is considered positive. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17178676&query_hl=1 ER - TY - JFULL T1 - Automatic cortical segmentation in the developing brain. A1 - Xue, H A1 - Srinivasan, L A1 - Jiang, S A1 - Rutherford, M A1 - Edwards, AD A1 - Rueckert, D A1 - Hajnal, JV J1 - Inf Process Med Imaging Y1 - 2007/// VL - 20 SN - 1011-2499 SP - 257 EP - 269 N2 - The segmentation of neonatal cortex from magnetic resonance (MR) images is much more challenging than the segmentation of cortex in adults. The main reason is the inverted contrast between grey matter (GM) and white matter (WM) that occurs when myelination is incomplete. This causes mislabeled partial volume voxels, especially at the interface between GM and cerebrospinal fluid (CSF). We propose a fully automatic cortical segmentation algorithm, detecting these mislabeled voxels using a knowledge-based approach and correcting errors by adjusting local priors to favor the correct classification. Our results show that the proposed algorithm corrects errors in the segmentation of both GM and WM compared to the classic EM scheme. The segmentation algorithm has been tested on 25 neonates with the gestational ages ranging from approximately 27 to 45 weeks. Quantitative comparison to the manual segmentation demonstrates good performance of the method (mean Dice similarity: 0.758 +/- 0.037 for GM and 0.794 +/- 0.078 for WM). L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17633705&query_hl=1 ER - TY - JFULL T1 - Can disease progression in non-alcoholic fatty liver disease be predicted by metabolic biomarkers of lipid accumulation and peroxidation? A1 - Cobbold, JF A1 - Anstee, QM A1 - Goldin, RD A1 - Cox, RD A1 - Thursz, MR A1 - Thomas, HC A1 - Taylor-Robinson, SD A1 - Cox, IJ J1 - J HEPATOL Y1 - 2007/01// VL - 46 SN - 0168-8278 SP - S265 EP - S265 ER - TY - JFULL T1 - Reference and target region modeling of [11C]-(R)-PK11195 brain studies. A1 - Turkheimer, FE A1 - Edison, P A1 - Pavese, N A1 - Roncaroli, F A1 - Anderson, AN A1 - Hammers, A A1 - Gerhard, A A1 - Hinz, R A1 - Tai, YF A1 - Brooks, DJ J1 - J Nucl Med Y1 - 2007/01// VL - 48 SN - 0161-5505 SP - 158 EP - 167 N2 - PET with [(11)C]-(R)-PK11195 is currently the modality of choice for the in vivo imaging of microglial activation in the human brain. In this work we devised a supervised clustering procedure and a new quantification methodology capable of producing binding potential (BP) estimates quantitatively comparable with those derived from plasma input with robust quantitative implementation at the pixel level. METHODS: The new methodology uses predefined kinetic classes to extract a gray matter reference tissue without specific tracer binding and devoid of spurious signals (in particular, blood pool and muscle). Kinetic classes were derived from an historical database of 12 healthy control subjects and from 3 patients with Huntington's disease. BP estimates were obtained using rank-shaping exponential spectral analysis (RS-ESA) (both plasma and reference input) and the simplified reference tissue model (SRTM). Comparison between plasma- derived BPs and those produced with the new reference methodology was performed using 6 additional healthy control subjects. Reliability of the new methodology was performed on 4 test-retest studies of patients with Alzheimer's disease. RESULTS: The new algorithm selected reference voxels in gray matter tissue avoiding regions with specific binding located, in particular, in the venous and arterial circulation. Using the new reference, BP values obtained using a plasma input and a reference input were in excellent agreement and highly correlated (r = 0.811, P < 10(-5)) when calculated with RS-ESA and less so (r = 0.507, P < 0.005) when SRTM was used. In the production of parametric maps, SRTM was used with the new reference extraction, resulting in test-retest variability (10.6%; mean ICC = 0.878) that was superior to that obtained using the previous unsupervised clustering approach (mean ICC = 0.596). CONCLUSION: Reference region modeling combined with supervised reference tissue extraction produces a robust and reproducible quantitative assessment of [(11)C]-(R)-PK11195 studies in the human brain. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17204713&query_hl=1 ER - TY - JFULL T1 - Investigation of myosin essential light chain in skeletal muscle fibres by fluorescence lifetime imaging microscopy. A1 - Ushakov, DS A1 - Konitsiotis, A A1 - Garcia, DI A1 - West, TG A1 - Auksorius, E A1 - Isidro, JR A1 - French, PM A1 - Ferenczi, MA J1 - BIOPHYS J Y1 - 2007/01// SN - 0006-3495 SP - 296A EP - 296A ER - TY - JFULL T1 - Flow measurement by magnetic resonance: a unique asset worth optimising. A1 - Kilner, PJ A1 - Gatehouse, PD A1 - Firmin, DN J1 - J Cardiovasc Magn Reson Y1 - 2007/// VL - 9 SN - 1097-6647 SP - 723 EP - 728 N2 - Users and manufacturers of cardiovascular magnetic resonance (CMR) systems have, potentially, an unrivalled asset. Phase contrast mapping of velocities through planes transecting the great arteries should provide the most accurate measurements available of cardiac output, shunt flow, aortic or pulmonary regurgitation and, indirectly, of mitral regurgitation. But the reality is that phase contrast velocity mapping remains under-used, and may have become discredited in the eyes of some CMR users and referring clinicians. Even when appropriate methods of acquisition have been used, there can be inaccuracies of flow measurement on some CMR systems caused by background phase errors due to eddy currents or uncorrected concomitant gradients. Measurements of regurgitant or shunt flow can be seriously affected by these errors which should be minimised or corrected by appropriate hardware and software design. If they have not been, inaccuracies can be detected and corrected by repeating identical velocity acquisitions on a static phantom, and subtracting the corresponding apparent phantom velocities from those of the clinical acquisition. For accurate measurements of aortic regurgitation or mitral inflow, motion tracking and velocity correction with respect to the cyclic displacements of the valves are needed, but few if any commercial systems provide this facility. Measurements of jet velocity pose different challenges, mainly related to the size and placement of voxels relative to a narrow jet. Awareness of the potential problems and concerted efforts towards optimisation are needed from manufacturers and users to make appropriate use of phase contrast flow measurement - a unique strength of cardiovascular magnetic resonance. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17613655&query_hl=1 ER - TY - JFULL T1 - Postoperative calculation of acetabular cup position using 2-D–3-D registration A1 - G.P. Penney A1 - P.J. Edwards A1 - J.H. Hipwell A1 - M. Slomczykowski A1 - I. Revie A1 - D.J. Hawkes J1 - IEEE Trans Biomed Eng Y1 - 2007/// IS - 7 VL - 54 PB - IEEE SN - 0018-9294 SP - 1342 EP - 1348 UR - http://ieeexplore.ieee.org/xpl/RecentIssue.jsp?punumber=10 ER - TY - JFULL T1 - Training and assessment of procedural skills in context using an Integrated Procedural Performance Instrument (IPPI). A1 - Kneebone, R A1 - Bello, F A1 - Nestel, D A1 - Yadollahi, F A1 - Darzi, A J1 - Stud Health Technol Inform Y1 - 2007/// VL - 125 SN - 0926-9630 SP - 229 EP - 231 N2 - The use of simulation in the training and assessment of procedural skills is widely acknowledged as a powerful and necessary alternative to the traditional apprenticeship model. However advanced, simulation on its own cannot provide the necessary conditions for holistic practice. The Integrated Procedural Performance Instrument presented in this paper combines simulated patients (SPs) with inanimate models, items of medical equipment or computer generated virtual models to recreate a panel of realistic scenarios, each addressing a combination of technical and non-technical clinical challenges. The result is a safe yet authentic clinical context which can be used for training and assessment. This novel use of simulation provides a patient-centred, learner-focused approach that builds up a composite picture of technical skills, communication skills and professional behaviours across a range of challenging clinical situations. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17377272&query_hl=1 ER - TY - JFULL T1 - Aspirin modified dendritic cells are potent inducers of allo-specific regulatory T-cells A1 - Buckland, M A1 - Jago, C A1 - Fazekesova, H A1 - George, A A1 - Lechler, R A1 - Lombardi, G J1 - INT IMMUNOPHARMACOL Y1 - 2006/12/20/ VL - 6 SN - 1567-5769 SP - 1895 EP - 1901 N2 - Salicylic acid (aspirin) is a widely used pharmacological agent with immunodmodulatory properties. Dendritic cells are key regulators of the immune response, and are capable of inducing hyporesponsiveness and regulatory activity in CD4(+) T-cells. We have demonstrated that aspirin-treated dendritic cells are effective at antigen processing and presentation, and possess a unique potency for inducing regulatory activity in responder T-cells. Unlike immature dendritic cells, aspirin DCs are resistant to the effects of maturational stimuli, as determined by low levels of CD40, CD80, CD83 and CD86 expression. Aspirin DCs were demonstrated to express high levels of the co-inhibitor of T-cell activation ILT-3. Aspirin DCs themselves produce less IL-10 and more IL-12 than immature DCs, but no specific cytokine is necessary for their tolerogenic capacity. When naive CD4(+) T-cells are exposed to aspirin DCs they produce significant levels of IFN gamma but these same T-cells are hypo-proliferative. Aspirin-treated DCs demonstrate the characteristics of a potential immunotherapy for controlling unwanted immune-responses Such as the indirect pathway of allo-recognition that drives chronic allograft rejection. (c) 2006 Elsevier B.V. All rights reserved. ER - TY - JFULL T1 - New developments of brain imaging for Parkinson's disease and related disorders. A1 - Piccini, P A1 - Brooks, DJ J1 - Mov Disord Y1 - 2006/12// VL - 21 SN - 0885-3185 SP - 2035 EP - 2041 N2 - Parkinson's disease (PD) and related disorders are subcortical degenerations targeting the nigrostriatal dopaminergic system and basal ganglia. Traditionally, MRI has been used to detect structural and positron emission tomography and single emission computed tomography functional neurochemical and metabolic changes associated with these disorders. Recently, advances in diffusion-weighted MRI, ultrasonography, and radiotracer-based imaging have yielded greater sensitivity for revealing structural change and allowed detection of changes in brain dopamine levels after levodopa and during behavioral tasks. This review focuses on these recent advances in neuroimaging technology and their use for the diagnosis and assessment of PD and other parkinsonian disorders. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16874751&query_hl=1 ER - TY - JFULL T1 - Using cerebral ultrasound effectively in the newborn infant. A1 - Leijser, LM A1 - de Vries, LS A1 - Cowan, FM J1 - Early Hum Dev Y1 - 2006/12// VL - 82 SN - 0378-3782 SP - 827 EP - 835 N2 - Cranial ultrasound is the most available and easily repeatable technique for imaging the neonatal brain. Its quality and diagnostic accuracy depend on various factors; the suitability of the ultrasound machine for neonatal cranial work, the use of optimal settings and probes, appropriate scanning protocols, the use of a variety of acoustic windows and, not least, the scanning experience of the examiner. Knowledge of normal anatomy and the echogenicities of different tissues in normal and pathological situations as well as familiarity with the physiological and pathological processes likely to be encountered is vital. This paper assesses the value and appropriate use, safety and diagnostic accuracy of modern, high-quality ultrasound in evaluating the brain of the preterm and term born infant. Issues of concern regarding teaching, supervision and experience of the examiner are also addressed. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17074450&query_hl=1 ER - TY - JFULL T1 - Reference right ventricular systolic and diastolic function normalized to age, gender and body surface area from steady-state free precession cardiovascular magnetic resonance. A1 - Maceira, AM A1 - Prasad, SK A1 - Khan, M A1 - Pennell, DJ J1 - Eur Heart J Y1 - 2006/12// VL - 27 SN - 0195-668X SP - 2879 EP - 2888 N2 - AIMS: Recent advances in cardiovascular magnetic resonance (CMR) include improved image quality with steady-state free precession (SSFP) sequences and advanced post-processing of high temporal resolution ventricular function. We used these techniques to establish the reference values for right ventricular (RV) volumes and function. METHODS AND RESULTS: We studied 120 healthy subjects (60 men, 60 women; from 20 to 80 years) after exclusion of cardiovascular abnormality. Data were generated from SSFP cines, with three-dimensional modelling. Gender, body surface area (BSA), and age were independent predictors of several RV parameters. Normalized RV mass (RVM) and absolute and normalized RV volumes decreased significantly with age, whereas ejection fraction increased. For diastolic variables, absolute and normalized early peak filling rate (PFR(E)) decreased and absolute and normalized active peak filling rate (PFR(A)) in males increased, with decreased PFR(E)/PFR(A). Increasing BSA was associated with increased RVM, volumes, and PFR(E). Gender significantly influenced absolute and normalized mass and volumes, and absolute and normalized PFR(A). CONCLUSION: These data using state-of-the-art CMR show that normal values of RV systolic and diastolic parameters vary significantly by gender, BSA, and age. Appropriate reference ranges normalized to all three variables should be used in the determination of normality or severity of abnormality of RV dimensions and function. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17088316&query_hl=1 ER - TY - JFULL T1 - Evaluation of carotid artery wall volume measurement using novel semiautomated analysis software. A1 - Varghese, A A1 - Merrifield, RD A1 - Crowe, LA A1 - Collins, SA A1 - Keenan, NG A1 - Firmin, DN A1 - Yang, GZ A1 - Pennell, DJ J1 - J Magn Reson Imaging Y1 - 2006/12// VL - 24 SN - 1053-1807 SP - 1401 EP - 1408 N2 - PURPOSE: To evaluate semiautomated analysis software for measuring the total carotid arterial wall volume (TWV) as a measure of atheroma burden. MATERIALS AND METHODS: Semiautomated-software and manual analyses of TWV measured by cardiovascular magnetic resonance (CMR) were compared in two phantom models, 10 subjects with no known carotid artery disease, and eight subjects with known carotid disease. The subjects were scanned twice for reproducibility. RESULTS: In subjects with no known carotid disease, semiautomated analysis of 98% of slices showed an improved interstudy coefficient of variation (COV) compared to manual analysis of 50% of slices (4.0% vs. 6.2%, P = 0.02). The proportion of matched cross-sectional slices usable for TWV measurement was superior (99% vs. 49%, P = 0.005) and the median analysis time was shorter (31 minutes vs. 90 minutes, P < 0.001) using the semiautomated software. In subjects with known carotid disease, semiautomated (99% of slices) and manual (56% of slices) analyses had comparable interstudy COVs (4.1% vs. 3.9%, P = 0.01). However, the proportion of matched cross-sectional slices usable for TWV measurement was greater using semiautomated contouring (96% vs. 56%, P = 0.01). CONCLUSION: Carotid CMR measurement of TWV using novel semiautomated analysis software shows good reproducibility, enables greater coverage of arterial vessel wall length, and is considerably faster compared to manual contouring. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17096390&query_hl=1 ER - TY - JFULL T1 - Smooth muscle cell proliferation but not neointimal formation is dependent on alloantibody in a murine model of intimal hyperplasia. A1 - Soleimani, B A1 - Katopodis, A A1 - Wieczorek, G A1 - George, AJ A1 - Hornick, PI A1 - Heusser, C J1 - Clin Exp Immunol Y1 - 2006/12// VL - 146 SN - 0009-9104 SP - 509 EP - 517 N2 - Transplant coronary artery disease is the pre-eminent cause of late cardiac allograft failure. It is primarily characterized by a concentric intimal hyperplasia, which we designate transplant intimal hyperplasia (TIH). Although the pathogenesis of TIH is predominately immune driven, the specific role of alloantibodies in the disease process remains undefined. In this study we investigated the contribution of alloantibodies to the development of TIH in a murine model. Orthotopic, carotid artery transplantation was performed between B10A(2R) (H-2(h2)) donor mice and B-cell deficient muMT(-/-) knockout or wild-type C57BL/6 (H-2(b)) recipients in the absence of immunosuppression. Grafts were harvested at 35 days and subjected to planimetry and immunohistochemistry. Alloantibodies were detectable in wild-type recipients within 7 days of transplantation and recipients developed marked TIH at 35 days. Allografts harvested from B-cell deficient recipient mice also developed TIH, which was comparable in severity with wild-type recipients. However, whereas allografts from wild-type recipients showed marked intimal smooth muscle cell (SMC) proliferation, the neointima in B-cell deficient recipients lacked SMCs. Post-transplantation administration of anti-donor serum to muMT(-/-) recipients restored neointimal SMC population but did not influence the severity of TIH. Significant neointimal formation occurs in the absence of alloantibodies but lacks a SMC component. Therefore, SMC migration and proliferation is antibody dependent. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17100772&query_hl=1 ER - TY - JFULL T1 - Automatic quantification of changes in bone in serial MR images of joints. A1 - Leung, KK A1 - Holden, M A1 - Saeed, N A1 - Brooks, KJ A1 - Buckton, JB A1 - Williams, AA A1 - Campbell, SP A1 - Changani, K A1 - Reid, DG A1 - Zhao, Y A1 - Wilde, M A1 - Rueckert, D A1 - Hajnal, JV A1 - Hill, DL J1 - IEEE Trans Med Imaging Y1 - 2006/12// VL - 25 SN - 0278-0062 SP - 1617 EP - 1626 N2 - Recent innovations in drug therapies have made it highly desirable to obtain sensitive biomarkers of disease progression that can be used to quantify the performance of candidate disease modifying drugs. In order to measure potential image-based biomarkers of disease progression in an experimental model of rheumatoid arthritis (RA), we present two different methods to automatically quantify changes in a bone in in-vivo serial magnetic resonance (MR) images from the model. Both methods are based on rigid and nonrigid image registration to perform the analysis. The first method uses segmentation propagation to delineate a bone from the serial MR images giving a global measure of temporal changes in bone volume. The second method uses rigid body registration to determine intensity change within a bone, and then maps these into a reference coordinate system using nonrigid registration. This gives a local measure of temporal changes in bone lesion volume. We detected significant temporal changes in local bone lesion volume in five out of eight identified candidate bone lesion regions, and significant difference in local bone lesion volume between male and female subjects in three out of eight candidate bone lesion regions. But the global bone volume was found to be fluctuating over time. Finally, we compare our findings with histology of the subjects and the manual segmentation of bone lesions. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17167996&query_hl=1 ER - TY - JFULL T1 - Left ventricular growth response to exercise and cigarette smoking: data from LARGE Heart A1 - Payne, JR A1 - Eleftheriou, KI A1 - James, LE A1 - Hawe, E A1 - Mann, J A1 - Stronge, A A1 - Kotwinski, P A1 - World, M A1 - Humphries, SE A1 - Pennell, DJ A1 - Montgomery, HE J1 - HEART Y1 - 2006/12// VL - 92 SN - 1355-6037 SP - 1784 EP - 1788 N2 - Background: Increasing left ventricular mass is a risk factor for cardiovascular morbidity and mortality.Objective: To examine the possible association of smoking with the left ventricular growth response in men.Methods: Left ventricular mass was measured in 309 army recruits before and after an identical 12-week physical training programme. Left ventricular mass was determined using cardiovascular magnetic resonance.Results: Left ventricular mass increased with training (mean (standard deviation (SD)) 3.83 (10.81) g, p < 0.001). By univariate analysis, exercise-induced change in left ventricular mass was positively associated with cigarette smoking (mean (SD) 1.69 (11.10) g v 4.76 (10.23) g for non-smokers vex- and current smokers, respectively; p = 0.026), whereas age, height, diastolic and systolic blood pressure (SBP), alcohol consumption or indices of physical activity were not significantly associated with change in left ventricular mass. Multivariate analysis showed body weight, smoking status and SBP to be independent predictors of left ventricular mass (incremental R-2 = 3.4%, p = 0.004; R-2 = 4.9%, p = 0.024; and R-2 = 1.7%, p = 0.041, respectively).Conclusions: Cigarette smoking and SBP are associated with exercise-induced left ventricular growth in young men. The positive association of smoking with changes in left ventricular mass is surprising, given the limited exposure of these subjects to smoking, and although these data do not prove causation, they are of great interest to those trying to uncover the drivers of left ventricular hypertrophy, as well as to those examining the possible ill-effects of smoking in the young. ER - TY - JFULL T1 - Investigating the nonlinear microbubble response to chirp encoded, multipulse sequences. A1 - Chetty, K A1 - Hajnal, JV A1 - Eckersley, RJ J1 - Ultrasound Med Biol Y1 - 2006/12// VL - 32 SN - 0301-5629 SP - 1887 EP - 1895 N2 - A modified Rayleigh-Plesset model was used to investigate the nonlinear acoustic response of ultrasound contrast microbubbles to multipulse phase and amplitude modulated, chirp encoded sequences. Trade-offs between the signal-to-noise ratio (SNR) and axial resolution were quantified for differing chirp time-bandwidth products and methods for minimising the artifacts formed in the postprocessing stages were developed. It was found that the chirp length can be increased and bandwidth reduced to improve SNR, though resolution is sacrificed. Results from the simulated chirp, pulse inverted, amplitude modulated (chirp PIAM) sequences were also compared with equivalent short pulse PIAM sequences and it was found that the chirp sequences preserve their extra energy after scattering, which translates to an improved SNR after processing. Compression artifacts were reduced by using chirps with a centre frequency and bandwidth tuned to the frequency response of the microbubble and reversing the frequency sweep of one chirp in the sequence. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17169700&query_hl=1 ER - TY - JFULL T1 - The neural correlates of declining performance with age: evidence for age-related changes in cognitive control. A1 - Sharp, DJ A1 - Scott, SK A1 - Mehta, MA A1 - Wise, RJ J1 - Cereb Cortex Y1 - 2006/12// VL - 16 SN - 1047-3211 SP - 1739 EP - 1749 N2 - The neural system involved in cognitive control includes the anterior cingulate cortex (ACC) and the lateral prefrontal cortex (PFC). Neural activity within these structures is sensitive to aging. We investigated the hypothesis that decline in performance with age results in increased cognitive control, as indexed by greater activity within the ACC and lateral PFC. Using positron emission tomography we measured neural activity during a range of verbal decision-making tasks in 16 subjects aged 37-83 years. Conditions were separated behaviorally on the basis of their sensitivity to aging. This allowed the comparison of age-dependent and age-independent conditions, revealing the neural correlates of age-dependent decline in performance. We then modeled the relationship between age, decision type, performance, and frontal lobe activity. ACC activity was independently predicted by age and decision-making accuracy, indicating that in older individuals ACC response is more sensitive to declining performance. We also found strong functional connectivity between the ACC and lateral PFC and observed that activation of the lateral PFC was qualitatively different over time in different age groups. Thus, the ACC and lateral PFC show distinct responses to age-related decline in decision-making performance. This suggests that greater cognitive control is employed as individuals age and their performance declines. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16407479&query_hl=1 ER - TY - JFULL T1 - Artifacts on electroencephalograms may influence the amplitude-integrated EEG classification: a qualitative analysis in neonatal encephalopathy. A1 - Hagmann, CF A1 - Robertson, NJ A1 - Azzopardi, D J1 - Pediatrics Y1 - 2006/12// VL - 118 SN - 1098-4275 SP - 2552 EP - 2554 N2 - This is a case report and a descriptive study demonstrating that artifacts are common during long-term recording of amplitude-integrated electroencephalograms and may lead to erroneous classification of the amplitude-integrated electroencephalogram trace. Artifacts occurred in 12% of 200 hours of recording time sampled from a representative sample of 20 infants with neonatal encephalopathy. Artifacts derived from electrical or movement interference occurred with similar frequency; both types of artifacts influenced the voltage and width of the amplitude-integrated electroencephalogram band. This is important knowledge especially if amplitude-integrated electroencephalogram is used as a selection tool for neuroprotection intervention studies. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17142543&query_hl=1 ER - TY - JFULL T1 - The role of cranial ultrasound and magnetic resonance imaging in the diagnosis of infections of the central nervous system. A1 - de Vries, LS A1 - Verboon-Maciolek, MA A1 - Cowan, FM A1 - Groenendaal, F J1 - Early Hum Dev Y1 - 2006/12// VL - 82 SN - 0378-3782 SP - 819 EP - 825 N2 - Imaging data concerning infection of the central nervous system (CNS) in neonates are usually confined to small groups of infants. We have reviewed the imaging findings in 96 preterm and full-term infants admitted to our neonatal intensive care unit over a 15 year period. Neuro-imaging, especially cranial ultrasound (CUS) and magnetic resonance imaging (MRI) provided useful information; CUS allows the early and later detection of calcification, germinolytic and parenchymal cysts, ventricular dilatation and strands and ependymal abnormality; diffusion weighted imaging (DWI) is especially useful in the acute stage of bacterial and viral infections, while conventional MRI helps in the detection of neocortical dysplasia in CMV infection and defining cerebellar abnormality. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17059873&query_hl=1 ER - TY - JFULL T1 - Manganese-enhanced magnetic resonance imaging (MEMRI) without compromise of the blood-brain barrier detects hypothalamic neuronal activity in vivo. A1 - Kuo, YT A1 - Herlihy, AH A1 - So, PW A1 - Bell, JD J1 - NMR Biomed Y1 - 2006/12// VL - 19 SN - 0952-3480 SP - 1028 EP - 1034 N2 - There is growing interest in the use of manganese-enhanced MRI (MEMRI) to detect neuronal activity and architecture in animal models. The MEMRI neuronal activity studies have been generally performed either by stereotactic brain injection or by systemic administration of Mn(2+) in conjunction with the disruption of the blood-brain barrier (BBB). These approaches, however, have limited the use of MEMRI because of the procedure-related morbidity/mortality or because brain activity measured by these methods can diverge from genuine physiological responses. In this study, the hypothesis that MEMRI, performed with systemic administration of Mn(2+) without compromising the BBB integrity, is able to detect hypothalamic function associated with feeding was tested. This procedure was tested on a simple physiological condition, fasting, and with this method temporal and regional differences in Mn(2+) enhancement could be detected. It is concluded that MEMRI can be used to study hypothalamic function in the murine brain without compromising the BBB. It was also shown that region-specific Mn(2+) enhancement in the mouse brain can be modulated by fasting. More importantly, this non-invasive in vivo imaging technique is able to demonstrate differences in brain activities, previously possible only by in vitro studies. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16845705&query_hl=1 ER - TY - JFULL T1 - Heartache in adolescence: non-invasive tissue characterization with cardiovascular magnetic resonance. A1 - Babu-Narayan, SV A1 - Kilner, PJ A1 - Magee, AG J1 - Cardiol Young Y1 - 2006/12// VL - 16 SN - 1047-9511 SP - 604 EP - 605 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17260425&query_hl=1 ER - TY - JFULL T1 - Mind the gap! What we don't know about right aortic arches and aberrant branches. A1 - Gardiner, HM J1 - Ultrasound Obstet Gynecol Y1 - 2006/12// VL - 28 SN - 0960-7692 SP - 868 EP - 869 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17121415&query_hl=1 ER - TY - JFULL T1 - Cardiovascular magnetic resonance, fibrosis, and prognosis in dilated cardiomyopathy. A1 - Assomull, RG A1 - Prasad, SK A1 - Lyne, J A1 - Smith, G A1 - Burman, ED A1 - Khan, M A1 - Sheppard, MN A1 - Poole-Wilson, PA A1 - Pennell, DJ J1 - J Am Coll Cardiol Y1 - 2006/11/21/ VL - 48 SN - 1558-3597 SP - 1977 EP - 1985 N2 - OBJECTIVES: We studied the prognostic implications of midwall fibrosis in dilated cardiomyopathy (DCM) in a prospective longitudinal study. BACKGROUND: Risk stratification of patients with nonischemic DCM in the era of device implantation is problematic. Approximately 30% of patients with DCM have midwall fibrosis as detected by late gadolinium-enhancement (LGE) cardiovascular magnetic resonance (CMR), which may increase susceptibility to arrhythmia and progression of heart failure. METHODS: Consecutive DCM patients (n = 101) with the presence or absence of midwall fibrosis were followed up prospectively for 658 +/- 355 days for events. RESULTS: Midwall fibrosis was present in 35% of patients and was associated with a higher rate of the predefined primary combined end point of all-cause death and hospitalization for a cardiovascular event (hazard ratio 3.4, p = 0.01). Multivariate analysis showed midwall fibrosis as the sole significant predictor of death or hospitalization. However, there was no significant difference in all-cause mortality between the 2 groups. Midwall fibrosis also predicted secondary outcome measures of sudden cardiac death (SCD) or ventricular tachycardia (VT) (hazard ratio 5.2, p = 0.03). Midwall fibrosis remained predictive of SCD/VT after correction for baseline differences in left ventricular ejection fraction between the 2 groups. CONCLUSIONS: In DCM, midwall fibrosis determined by CMR is a predictor of the combined end point of all-cause mortality and cardiovascular hospitalization, which is independent of ventricular remodeling. In addition, midwall fibrosis by CMR predicts SCD/VT. This suggests a potential role for CMR in the risk stratification of patients with DCM, which may have value in determining the need for device therapy. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17112987&query_hl=1 ER - TY - JFULL T1 - Cardiovascular magnetic resonance in arrhythmogenic right ventricular cardiomyopathy revisited: comparison with task force criteria and genotype. A1 - Sen-Chowdhry, S A1 - Prasad, SK A1 - Syrris, P A1 - Wage, R A1 - Ward, D A1 - Merrifield, R A1 - Smith, GC A1 - Firmin, DN A1 - Pennell, DJ A1 - McKenna, WJ J1 - J Am Coll Cardiol Y1 - 2006/11/21/ VL - 48 SN - 1558-3597 SP - 2132 EP - 2140 N2 - OBJECTIVES: We sought to assess the utility of cardiovascular magnetic resonance (CMR) in the evaluation of arrhythmogenic right ventricular cardiomyopathy (ARVC) in relation to diagnostic criteria and genotype. BACKGROUND: Timely diagnosis of ARVC is difficult as clinical findings may be subtle and nonspecific in early disease. The role of CMR is controversial owing to the absence of a standardized protocol, insufficient experience with the modality, and inherent difficulties in imaging the right ventricle. METHODS: Comprehensive CMR examination was performed in 232 patients undergoing evaluation for suspected ARVC. CMR outcomes were compared with: 1) prospective clinical diagnosis using Task Force guidelines, with and without the proposed modifications for familial ARVC; and 2) gene-carrier status in 35 individuals from genotyped families. RESULTS: CMR studies were positive in all 64 patients who prospectively fulfilled Task Force criteria, resulting in 100% sensitivity. Specificity in relation to Task Force criteria was low (29%). Of the 119 apparent false positives detected by CMR, however, 63 fulfilled modified diagnostic criteria for familial ARVC and 7 were obligate gene carriers, suggesting that CMR frequently identifies individuals with early disease, in whom Task Force criteria are relatively insensitive. This was borne out by evaluation of genotyped individuals (26 gene-positive and 9 gene-negative), in whom CMR had a sensitivity of 96% and a specificity of 78%. CONCLUSIONS: CMR is a valuable component of the diagnostic workup for ARVC when performed with a dedicated protocol by specialists with experience in analysis of volumes, right ventricular wall motion, and delayed-enhancement imaging. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17113003&query_hl=1 ER - TY - JFULL T1 - Differential hypothalamic neuronal activation following peripheral injection of GLP-1 and oxyntomodulin in mice detected by manganese-enhanced magnetic resonance imaging. A1 - Chaudhri, OB A1 - Parkinson, JR A1 - Kuo, YT A1 - Druce, MR A1 - Herlihy, AH A1 - Bell, JD A1 - Dhillo, WS A1 - Stanley, SA A1 - Ghatei, MA A1 - Bloom, SR J1 - Biochem Biophys Res Commun Y1 - 2006/11/17/ VL - 350 SN - 0006-291X SP - 298 EP - 306 N2 - The anorexigenic gut hormones oxyntomodulin (OXM) and glucagon-like peptide-1 (GLP-1) are thought to physiologically regulate appetite and food intake. Using manganese-enhanced magnetic resonance imaging, we have shown distinct patterns of neuronal activation in the hypothalamus in response to intraperitoneal injections into fasted mice of 900 and 5400 nmol/kg OXM or 900 nmol/kg GLP-1. Administration of OXM at either dose resulted in a reduced rate of signal enhancement, reflecting a reduction in neuronal activity, in the arcuate, paraventricular, and supraoptic nuclei of the hypothalamus. Conversely, GLP-1 caused a reduction in signal enhancement in the paraventricular nucleus only and an increase in the ventromedial hypothalamic nucleus. Our data show that these two apparently similar peptides generate distinct patterns of activation within the hypothalamus, suggesting that GLP-1 and OXM may act via different hypothalamic pathways. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17007819&query_hl=1 ER - TY - JFULL T1 - Imaging molecular and cellular events in transplantation. A1 - George, AJ A1 - Bhakoo, KK A1 - Haskard, DO A1 - Larkman, DJ A1 - Reynolds, PR J1 - Transplantation Y1 - 2006/11/15/ VL - 82 SN - 0041-1337 SP - 1124 EP - 1129 N2 - Imaging methods such as nuclear medicine (including positron emission tomography), magnetic resonance imaging, ultrasound, and optical imaging can be used to provide information about the expression of genes, and the location of molecules and cells in intact animals or patients. In the setting of transplantation, this will allow monitoring of inflammatory responses, as well as the state of the graft. In this review, the advantages and disadvantages of different approaches to imaging will be discussed, as well as their potential application to transplantation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17102760&query_hl=1 ER - TY - JFULL T1 - Clinical correlates of levodopa-induced dopamine release in Parkinson disease: a PET study. A1 - Pavese, N A1 - Evans, AH A1 - Tai, YF A1 - Hotton, G A1 - Brooks, DJ A1 - Lees, AJ A1 - Piccini, P J1 - Neurology Y1 - 2006/11/14/ VL - 67 SN - 1526-632X SP - 1612 EP - 1617 N2 - OBJECTIVE: To evaluate the relationship between clinical improvement and in vivo synaptic dopamine (DA) release after a single oral dose of levodopa (LD) in patients with advanced Parkinson disease (PD). METHODS: We studied 16 patients with advanced PD with [(11)C]raclopride (RAC) PET. Each patient had RAC PET twice: once when medication had been withdrawn and once after an LD challenge. On the day of the LD challenge scan, oral 250 mg LD/25 mg carbidopa was given before scanning. Unified Parkinson's Disease Rating Scale (UPDRS) motor scores were rated in an "off" state before LD and again at the end of PET. RESULTS: All the patients were still in "on" state at the end of their LD challenge RAC PET scans. Following LD, mean caudate and putamen RAC binding potentials (BPs) were significantly lower vs baseline, consistent with increased synaptic DA. Individual LD-induced improvements in UPDRS score correlated significantly with reductions in putaminal BP. Additionally, large putaminal RAC BP changes were associated with higher dyskinesia scores. When motor UPDRS subitems were examined, improvements in rigidity and bradykinesia, but not in tremor or axial symptoms, correlated with putamen DA release. CONCLUSION: In advanced Parkinson disease, the improvement of rigidity and bradykinesia and the presence of dyskinesias after a single dose of oral levodopa are governed by the level of dopamine generated at striatal D2 receptors. In contrast, relief of parkinsonian tremor and axial symptoms is not related to striatal synaptic dopamine levels and presumably occurs via extrastriatal mechanisms. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17101892&query_hl=1 ER - TY - JFULL T1 - Fetal ECG: A Novel Predictor of Atrioventricular Block in Anti-Ro Positive Pregnancies. A1 - Gardiner, HM A1 - Belmar, C A1 - Pasquini, L A1 - Seale, A A1 - Thomas, MJ A1 - Dennes, W A1 - Taylor, MJ A1 - Kulinskaya, E A1 - Wimalasundera, R J1 - Heart Y1 - 2006/11/03/ SN - 1468-201X N2 - Objective Approximately 2.8% of pregnancies are Ro /La antibody positive. Three to 15% fetuses develop complete heart block (CHB). First degree atrioventricular heart block (10 AVB) is reported in a third of Ro/La fetuses but as most have normal postnatal ECG may reflect inadequacies of Doppler measurement techniques. Design We compared mechanical (mPR) and electrical (ePR) intervals obtained prospectively using Doppler and non-invasive fetal ECG (fECG) in 52 consecutive Ro/La pregnancies in 46 women carrying 54 fetuses in an observational study. Setting Fetal Medicine Unit Methods & results We recorded 121 mPR and 37 ePR intervals in 49 Ro/La fetuses. Five were referred with CHB and excluded. ePR was measured successfully in 35/ 37 (94%) and mPR in all. 10 AVB was defined as PR > 95% CI. Logistic regression predicted abnormal final fetal rhythm from first mPR or ePR. ePR model gave 66.7% sensitivity (6 of 8 final abnormal fetal rhythm cases predicted correctly in fetuses >20 weeks) and 96.2% specificity and mPR 44.4% sensitivity (4 of 9 cases) and 88.5% specificity. Z scores for ePR (zPR) were calculated from 199 normal fetuses. Area under ROC curve was 0.88 (95% CI 0.754,1.007). A cut-off of 1.65 gave sensitivity of 87.5% and specificity of 95% for those with prolonged and normal ePR intervals respectively. Conclusions zPR is better than mPR in differentiating between normal and prolonged PR interval suggesting fECG is the diagnostic tool of choice to investigate the natural history and therapy of conduction abnormalities in Ro/La pregnancies. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17085531&query_hl=1 ER - TY - JFULL T1 - Opioid imaging. A1 - Hammers, A A1 - Lingford-Hughes, A J1 - Neuroimaging Clin N Am Y1 - 2006/11// VL - 16 SN - 1052-5149 SP - 529 EP - 552 N2 - Many breakthrough scientific discoveries have been made using opioid imaging, particularly in the fields of pain, addiction and epilepsy research. Recent developments include the application of ever higher resolution whole-brain positron emission tomography (PET) scanners, the availability of several radioligands, the combination of PET with advanced structural imaging, advances in modeling macroparameters of PET ligand binding, and large-scale statistical analysis of imaging datasets. Suitable single-photon emission computed tomography (SPECT) tracers are lacking, but with the increase in the number of available PET (or PET/CT) cameras and cyclotrons thanks to the clinical successes of PET in oncology, PET may become widespread enough to overcome this limitation. In the coming decade, we hope to see a more widespread application of the techniques developed in healthy volunteers to patients and more clinical impact of opioid imaging. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17148018&query_hl=1 ER - TY - JFULL T1 - Knockdown of mouse VCAM-1 by vector-based siRNA. A1 - Alam, AK A1 - Florey, O A1 - Weber, M A1 - Pillai, RG A1 - Chan, C A1 - Tan, PH A1 - Lechler, RI A1 - McClure, MO A1 - Haskard, DO A1 - George, AJ J1 - Transpl Immunol Y1 - 2006/11// VL - 16 SN - 0966-3274 SP - 185 EP - 193 N2 - Graft rejection is critically dependent on the recruitment of leukocytes via adhesion molecules on the endothelium, and inhibition of these interactions can prolong graft survival. We have therefore developed an approach using siRNA to inhibit the expression of VCAM-1 in endothelial cells. We transfected siRNA constructs into murine corneal and vascular endothelium and looked at expression of VCAM-1 and other surface molecules by flow cytometry. Adhesion assays (both static and under flow) were used to determine the effect of VCAM-1 inhibition. The activation of cellular stress responses was assessed by RT-PCR. Constructs encoding siRNA can block expression of VCAM-1 in both corneal and vascular endothelial cells (in the latter case after cytokine stimulation). Inhibition of VCAM-1 expression reduced the ability of T cells to adhere to endothelium. However, there were non-specific effects of siRNA expression, including upregulation of (Programmed Death Ligand 1) PDL1 and decreased cell growth. Analysis of stress pathways showed that the endothelial cells transfected with siRNA had upregulated molecules associated with cell stress. While these data are supportive of a potential therapeutic role for siRNA constructs in blocking the expression of adhesion molecules, they also highlight potential non-specific effects of siRNA that must be carefully considered in any application of this technology. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17138052&query_hl=1 ER - TY - JFULL T1 - Conceptual framework for laparoscopic VR simulators. A1 - Lamata, P A1 - Gómez, EJ A1 - Bello, F A1 - Kneebone, RL A1 - Aggarwal, R A1 - Lamata, F J1 - IEEE Comput Graph Appl Y1 - 2006/11// VL - 26 SN - 0272-1716 SP - 69 EP - 79 N2 - Availability of YR laparoscopic simulation for surgical training has increased significantly. Nevertheless, few studies have explored such simulators' requirements and the degree of fidelity necessary to provide effective educational tools. The authors aim to identify which didactic resources available in YR simulation technologies are most important for laparoscopic training. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17120915&query_hl=1 ER - TY - JFULL T1 - T2* effects in the dual-sequence method for high-dose first-pass myocardial perfusion. A1 - Gatehouse, P A1 - Lyne, J A1 - Smith, G A1 - Pennell, D A1 - Firmin, D J1 - J Magn Reson Imaging Y1 - 2006/11// VL - 24 SN - 1053-1807 SP - 1168 EP - 1171 N2 - PURPOSE: To examine whether T2* effects reduce the accuracy of arterial input function (AIF) measurement by the dual-sequence method. MATERIALS AND METHODS: The dual-sequence method obtains a low-resolution AIF image and high-resolution myocardial images in each cycle, with suitable T1 weightings. It was modified to assess T2* effects in the low-resolution AIF image (4.8x4.8x10 mm voxels, TE=0.58 msec) by minimizing T1 weighting in that sequence, while the myocardial sequence remained T1-weighted. In 10 patients who underwent perfusion MRI scans (0.5 M Magnevist, 0.1 mmol/kg, 15-ml flush, 7 mL/second right antecubital) the blood signal in the left ventricle (LV) was measured at the bolus peak and compared with the first cycle's fresh magnetization signal. RESULTS: The bolus peak measured 98%+/-4% (mean+/-SD, N=20) of the value before contrast agent arrival. CONCLUSION: T2* causes insignificant error in the dual-sequence method at the stated parameters. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17031839&query_hl=1 ER - TY - JFULL T1 - Re: Palliation bias is being overlooked in neonatal hypothermia trials. A1 - Edwards, AD A1 - Azzopardi, DV J1 - Arch Dis Child Fetal Neonatal Ed Y1 - 2006/11// VL - 91 SN - 1359-2998 SP - F465 N2 - L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17056853&query_hl=1 ER - TY - JFULL T1 - Sustainable use of continuous positive airway pressure in extremely preterm infants during the first week after delivery. A1 - Booth, C A1 - Premkumar, MH A1 - Yannoulis, A A1 - Thomson, M A1 - Harrison, M A1 - Edwards, AD J1 - Arch Dis Child Fetal Neonatal Ed Y1 - 2006/11// VL - 91 SN - 1359-2998 SP - F398 EP - F402 N2 - BACKGROUND: Early use of nasal continuous positive airway pressure (nCPAP) may reduce lung damage, but it is not clear how many extremely preterm infants can be cared for without mechanical ventilation on the first days after delivery. OBJECTIVES: To describe our experience of nCPAP in infants born at <27 weeks' gestation and to determine the chance of reintubation of this group of extremely preterm infants. METHODS: A retrospective, observational study examined the period from November 2002 to October 2003, when efforts were made to extubate infants to nCPAP at the earliest opportunity. Data were collected on all infants born at <27 weeks' and gestation admitted to The Neonatal Intensive Care Unit, Queen Charlotte's and Chelsea Hospital, London, UK. The chance of an individual infant requiring reintubation within 48 h of delivery was estimated, calculating the predictive probability using a Bayesian approach, and oxygen requirements at 36 weeks' postmenstrual age were examined. RESULTS: 60 infants, 34 inborn and 26 ex utero transfers, were admitted; 7 infants admitted 24 h after birth were excluded and 5 died within 48 h. The mean birth weight was 788 g and the gestational age was 25.3 weeks. Extubation was attempted on day 1 in 21 of 52 infants on ventilators and was successful in 14; and on day 2 in 14 of 35 and successful in 10 of infants extubated within 48 h of delivery survived to discharge. 5 of 23 infants on mechanical ventilation at 48 h of age were on air at 36 weeks postmenstrual age, and 12 of 26 of those were on nCPAP at 48 h of age. The probability of an individual baby remaining on nCPAP was 66% (95% CI 46% to 86%) on day 1 and 80% (95% CI 60% to 99%) on day 2. The smallest infant to be successfully extubated was 660 g and the youngest gestational age was 23.8 weeks. CONCLUSIONS: Extremely preterm infants can be extubated to nCPAP soon after delivery, with a reasonable probability of not requiring immediate reintubation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16820391&query_hl=1 ER - TY - JFULL T1 - Development of dyskinesias in a 5-year trial of ropinirole and L-dopa A1 - Rascol, O A1 - Brooks, DJ A1 - Korczyn, AD A1 - De Deyn, PP A1 - Clarke, CE A1 - Lang, AE A1 - Abdalla, M A1 - 056 Study Grp J1 - MOVEMENT DISORD Y1 - 2006/11// VL - 21 SN - 0885-3185 SP - 1844 EP - 1850 N2 - A 5-year trial of ropinirole and levodopa in early Parkinson's disease showed that ropinirole is associated with reduced incidence of dyskinesias. This post hoc analysis investigated whether the dyskinesia-sparing benefit of ropinirole is lost when levodopa is added to the regimen and evaluated other risk factors for developing dyskinesias. Patients receiving levodopa had a significantly higher risk of dyskinesias than those taking ropinirole monotherapy (hazard ratio [HR], 6.67; 95% confidence interval [CI], 3.23-14.29; P < 0.001). When patients randomized to ropinirole were treated with supplementary levodopa, the development of dyskinesias was not significantly different from that in those receiving levodopa from the start (HR, 0.80; 95% CI, 0.48-1.33; P = 0.39). However, the onset of dyskinesias was delayed by around 3 years compared with levodopa monotherapy. Adjusted analyses taking into account baseline and on-treatment factors that influenced use of supplementary levodopa or the development of dyskinesias produced similar results. In conclusion, the risk of developing dyskinesias during maintained initial ropinirole monotherapy is very low. Only once levodopa is added does the risk substantially change. Early use of ropinirole postpones the onset of dyskinesias, but these benefits decline when levodopa therapy is started, with no evidence of a subsequent rapid "catch-up" or a persisting preventive effect. (c) 2006 Movement Disorder Society. ER - TY - JFULL T1 - Online remeshing for soft tissue simulation in surgical training. A1 - Paloc, C A1 - Faraci, A A1 - Bello, F J1 - IEEE Comput Graph Appl Y1 - 2006/11// VL - 26 SN - 0272-1716 SP - 24 EP - 34 N2 - To graphically model and animate the realistic behavior of deformable tissue in surgical simulations, the authors' system adapts tetrahedra resolution by dynamically retessellating the mesh in and around the regions of interest. This technique overcomes limitations of previous methods that made it difficult to modify the mesh's topology online. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17120911&query_hl=1 ER - TY - JFULL T1 - Nonlinear phase correction of navigated multi-coil diffusion images. A1 - Atkinson, D A1 - Counsell, S A1 - Hajnal, JV A1 - Batchelor, PG A1 - Hill, DL A1 - Larkman, DJ J1 - Magn Reson Med Y1 - 2006/11// VL - 56 SN - 0740-3194 SP - 1135 EP - 1139 N2 - Cardiac pulsatility causes a nonrigid motion of the brain. In multi-shot diffusion imaging this leads to spatially varying phase changes that must be corrected. A conjugate gradient based reconstruction is presented that includes phase changes measured using two-dimensional navigator echoes, coil sensitivity information, navigator-determined weightings, and data from multiple coils and averages.A multi-shot echo planar sequence was used to image brain regions where pulsatile motion is not uniform. Reduced susceptibility artifacts were observed compared to a clinical single-shot sequence. In a higher slice, fiber directions derived from single-shot data show distortions from anatomical scans by as much as 7 mm compared to less than 2 mm for our multi-shot reconstructions. The reduced distortions imply that phase encoding can be applied in the shorter left-right direction, enabling time savings through the use of a rectangular field of view. Higher resolution diffusion imaging in the spine permits visualization of a nerve root. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16986111&query_hl=1 ER - TY - JFULL T1 - Severe endothelial dysfunction in young women with polycystic ovary syndrome is only partially explained by known cardiovascular risk factors. A1 - Sorensen, MB A1 - Franks, S A1 - Robertson, C A1 - Pennell, DJ A1 - Collins, P J1 - Clin Endocrinol (Oxf) Y1 - 2006/11// VL - 65 SN - 0300-0664 SP - 655 EP - 659 N2 - OBJECTIVE: We aimed to assess whether metabolic abnormalities can explain endothelial dysfunction and associated cardiovascular disease risk (CVDr) in polycystic ovary syndrome (PCOS). Endothelial function, a recognized composite marker of CVDr, may be reduced in PCOS and can be precisely and noninvasively assessed by cardiovascular magnetic resonance (CMR). PATIENTS: Fourteen women with anovulatory PCOS (age [mean +/- SD] 33 +/- 4 years) and 13 controls (age: 33 +/- 6 years) with similar body mass index and regular menses. METHODS: Endothelium-dependent (flow-mediated dilatation - FMD) and -independent (glyceryl trinitrate - GTN) changes in the brachial artery area were measured using CMR in women with PCOS and controls. Arterial function was assessed twice, in the early follicular phase and mid cycle in controls and after an interval of 2 weeks in PCOS subjects. Fasting lipids, glucose, insulin and sex hormones were measured at the first visit. RESULTS: FMD was greatly reduced in women with PCOS compared to controls (-1%vs 5% and 2%vs 12%, P < 0.01) without differences in GTN responses. Risk factors were more prevalent in PCOS women and displayed significant linear relationships with FMD. PCOS status was the strongest predictor of FMD. Linear regression between PCOS and FMD remained significant after correction for all CVD risk markers linked to the metabolic syndrome. CONCLUSION: PCOS is associated with changes in CVD risk markers and pronounced endothelial dysfunction. However endothelial dysfunction with PCOS is only partly explained by recognized CVD risk markers. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17054469&query_hl=1 ER - TY - JFULL T1 - Passive properties of the diaphragm in COPD. A1 - Moore, AJ A1 - Stubbings, A A1 - Swallow, EB A1 - Dusmet, M A1 - Goldstraw, P A1 - Porcher, R A1 - Moxham, J A1 - Polkey, MI A1 - Ferenczi, MA J1 - J Appl Physiol Y1 - 2006/11// VL - 101 SN - 8750-7587 SP - 1400 EP - 1405 N2 - Structural adaptations that occur in the diaphragm muscle of patients with chronic obstructive pulmonary disease (COPD), namely an increase in type I fibers and a decrease in type II fibers, have been explored in terms of the active contractile properties of the diaphragm. The aim of this study was to test the passive properties of the diaphragm by measuring the force response of relaxed diaphragm muscle fibers to stretching to determine the effect of COPD on these properties. Costal diaphragm biopsies were taken from patients with COPD and from controls with normal pulmonary function. From these biopsies, titin expression was assessed in diaphragm homogenates by gel electrophoresis, and the restoring force was measured by incremental stretching of single fibers in the relaxed state and measuring the force response to stretching. A quadratic model was used to illustrate the relationship between restoring force and muscle fiber length, and it revealed that COPD fibers generate significantly lower restoring forces than control fibers as judged by the area under the force-length curve. Furthermore, this finding applies to both type I and type II fibers. Gel electrophoresis revealed different titin isoforms in COPD and controls, consistent with the conclusion that COPD results not only in a change in muscle fiber-type distribution but in a structural change in the titin molecule in all muscle fiber types within the diaphragm. This may assist the muscle with the energetic changes in the length of the diaphragm required during breathing in COPD. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16840573&query_hl=1 ER - TY - JFULL T1 - Detection of vascular expression of E-selectin in vivo with MR imaging. A1 - Reynolds, PR A1 - Larkman, DJ A1 - Haskard, DO A1 - Hajnal, JV A1 - Kennea, NL A1 - George, AJ A1 - Edwards, AD J1 - Radiology Y1 - 2006/11// VL - 241 SN - 0033-8419 SP - 469 EP - 476 N2 - PURPOSE: To develop a contrast agent for targeting E-selectin expressed on activated vascular endothelium and to evaluate detection of the agent with magnetic resonance (MR) imaging in an in vivo mouse model of inflammation. MATERIALS AND METHODS: All animal experiments were approved according to animal welfare and local ethics committee regulations. An anti-murine E-selectin F(ab')2 monoclonal antibody, MES-1, was conjugated with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles. Flow cytometry, Perl Prussian blue staining for iron, and MR imaging were performed by using Chinese hamster ovary (CHO) cells expressing mouse E-selectin to detect binding of the conjugate in vitro, and a mouse model of contact hypersensitivity to oxazolone in the ear was used to investigate the in vivo characteristics of the MES-1-USPIO. Serial imaging was performed by using a 9.4-T MR imaging system with a custom receive-only coil. Tissue slices were stained to define distribution of E-selectin expression and localization of the MES-1-USPIO conjugate. RESULTS: MES-1-USPIO was shown to bind to CHO cells expressing mouse E-selectin in vitro. After injection of MES-1-USPIO in vivo, distinct changes in R2 relaxation rate (1/T2) characteristics were detected in inflamed ears when they were compared with control ears. Histologic analysis confirmed the vascular endothelial distribution of MES-1-USPIO. CONCLUSION: E-selectin expression in vivo can be selectively and directly imaged noninvasively with MR. This has the potential to be useful in the study of inflammatory disease. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17005768&query_hl=1 ER - TY - JFULL T1 - Non-invasive evaluation of hepatic fibrosis using magnetic resonance and ultrasound techniques. A1 - Cobbold, JF A1 - Wylezinska, M A1 - Cunningham, C A1 - Crossey, ME A1 - Thomas, HC A1 - Cox, IJ A1 - Patel, N A1 - Taylor-Robinson, SD J1 - Gut Y1 - 2006/11// VL - 55 SN - 0017-5749 SP - 1670; author reply 1670 EP - 1670; author reply 1670 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17047120&query_hl=1 ER - TY - JFULL T1 - Two Diverticula of the Left Ventricular Outflow Tract Adjacent to the Commissures of a Bicuspid Aortic Valve A1 - Krishnan U A1 - Kilner PJ A1 - Money-Kyrle A A1 - Ramrakha P J1 - Congenital Heart Disease Y1 - 2006/11// IS - 6 VL - 1 PB - Blackwell SP - 332 EP - 334 UR - http://www.ingentaconnect.com/content/bsc/chd/2006/00000001/00000006/art00011;jsessionid=8s0jrqg3i52r.victoria ER - TY - JFULL T1 - Myocardial insulin sensitivity correlates with sympathetic drive in patients with left ventricular dysfunction A1 - Mongillo, M A1 - John, A A1 - Rimoldi, O A1 - Pennell, D A1 - Camici, PG J1 - CIRCULATION Y1 - 2006/10/31/ VL - 114 SN - 0009-7322 SP - 804 EP - 804 ER - TY - JFULL T1 - ACE inhibitors for potential prevention of the deleterious effects of pulmonary regurgitation in adults with tetralogy of Fallot repair - the approriate study - a randomised, double-blinded, placebo-controlled trial in adults with congenital heart disease A1 - Babu-Narayan, SV A1 - Uebing, A A1 - Davlouros, PA A1 - Kemp, M A1 - Davidson, S A1 - Goktekin, O A1 - Bayne, S A1 - Kilner, PJ A1 - Li, W A1 - Gatzoulis, MA J1 - CIRCULATION Y1 - 2006/10/31/ VL - 114 SN - 0009-7322 SP - 413 EP - 413 ER - TY - JFULL T1 - Myocardial tissue Doppler and long axis function in the fetal heart. A1 - Gardiner, HM A1 - Pasquini, L A1 - Wolfenden, J A1 - Barlow, A A1 - Li, W A1 - Kulinskaya, E A1 - Henein, M J1 - Int J Cardiol Y1 - 2006/10/26/ VL - 113 SN - 1874-1754 SP - 39 EP - 47 N2 - Current echocardiographic assessment of fetal ventricular function uses relatively crude measures and this has led to inconsistencies in assessment of diastolic function. Long axis parameters may be more insightful. OBJECTIVE: To describe fetal long axis cardiac function and construct reference ranges. DESIGN: 159 normal fetuses were studied cross-sectionally using long axis M-mode to measure displacement of the atrioventricular ring and pulsed wave Doppler ultrasound to record myocardial tissue Doppler velocities at the base of the heart. RESULTS: There was a strong, almost linear gestational relationship for all but late left basal myocardial velocities. Systolic amplitude of the atrioventricular ring increased significantly. Wall thickness increased with gestation and heart rate reduced. Late diastolic mitral and tricuspid flow velocities showed no age-dependence. Right ventricular filling (p<0.0001) and myocardial lengthening (p<0.0001) and shortening velocities (p<0.0001) were higher than left. Aortic velocities were higher than pulmonary (p<0.0001). Right ventricular long axis amplitude was greater than left (p<0.0001). There were no significant differences in right (RV) and left (LV) ventricular and septal thicknesses (RV 2.5 mm [1.2-4.1]; LV (2.4 mm [1.0-4.0] and septum 2.6 mm [1.0-4.3]). Left and right myocardial tissue Doppler velocities showed similar maturation in systole (LV 0.14 vs. RV 0.10 cm/s/week) and early diastole (LV 0.16 vs. RV 0.14 cm/s/week). CONCLUSIONS: This study demonstrates maturational changes occur in both fetal systolic and diastolic ventricular function and moreover the maturational rate of myocardial tissue velocities is similar in both ventricles, despite differential loading conditions. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16360223&query_hl=1 ER - TY - JFULL T1 - Automatic anatomical brain MRI segmentation combining label propagation and decision fusion. A1 - Heckemann, RA A1 - Hajnal, JV A1 - Aljabar, P A1 - Rueckert, D A1 - Hammers, A J1 - Neuroimage Y1 - 2006/10/15/ VL - 33 SN - 1053-8119 SP - 115 EP - 126 N2 - Regions in three-dimensional magnetic resonance (MR) brain images can be classified using protocols for manually segmenting and labeling structures. For large cohorts, time and expertise requirements make this approach impractical. To achieve automation, an individual segmentation can be propagated to another individual using an anatomical correspondence estimate relating the atlas image to the target image. The accuracy of the resulting target labeling has been limited but can potentially be improved by combining multiple segmentations using decision fusion. We studied segmentation propagation and decision fusion on 30 normal brain MR images, which had been manually segmented into 67 structures. Correspondence estimates were established by nonrigid registration using free-form deformations. Both direct label propagation and an indirect approach were tested. Individual propagations showed an average similarity index (SI) of 0.754+/-0.016 against manual segmentations. Decision fusion using 29 input segmentations increased SI to 0.836+/-0.009. For indirect propagation of a single source via 27 intermediate images, SI was 0.779+/-0.013. We also studied the effect of the decision fusion procedure using a numerical simulation with synthetic input data. The results helped to formulate a model that predicts the quality improvement of fused brain segmentations based on the number of individual propagated segmentations combined. We demonstrate a practicable procedure that exceeds the accuracy of previous automatic methods and can compete with manual delineations. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16860573&query_hl=1 ER - TY - JFULL T1 - Multi-center validation of the transferability of the magnetic resonance T2* technique for the quantification of tissue iron. A1 - Tanner, MA A1 - He, T A1 - Westwood, MA A1 - Firmin, DN A1 - Pennell, DJ A1 - Thalassemia International Federation Heart T2* Investigators J1 - Haematologica Y1 - 2006/10// VL - 91 SN - 1592-8721 SP - 1388 EP - 1391 N2 - The transferability of the T2* technique for measurement of tissue iron between magnetic resonance (MR) scanners is unknown. Heart and liver multi-breath-hold T2* sequences were installed on MR scanners at six different sites. T2* was assessed locally in five or more patients with thalassemia major (n=39), and subjects were re-scanned at the standardization center in London. Inter-center reproducibility of T2* in heart and liver was 5.0% and 7.1%, with mean absolute differences in T2* of 1.3 ms and 0.45 ms, respectively. The MR multi-breath-hold T2* technique for tissue iron quantification is transferable between scanners with good reproducibility. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17018390&query_hl=1 ER - TY - JFULL T1 - Myocardial ischemia and right ventricular dysfunction in adult patients with sickle cell disease. A1 - Pennell, D J1 - Haematologica Y1 - 2006/10// VL - 91 SN - 1592-8721 SP - 1298A N2 - L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17018369&query_hl=1 ER - TY - JFULL T1 - x-f Choice: reconstruction of undersampled dynamic MRI by data-driven alias rejection applied to contrast-enhanced angiography. A1 - Malik, SJ A1 - Schmitz, S A1 - O'Regan, D A1 - Larkman, DJ A1 - Hajnal, JV J1 - Magn Reson Med Y1 - 2006/10// VL - 56 SN - 0740-3194 SP - 811 EP - 823 N2 - A technique for reconstructing dynamic undersampled MRI data, termed "x-f choice," was developed and applied to dynamic contrast-enhanced MR angiography (DCE-MRA). Regular undersampling in k-t space (a hybrid of k-space and time) creates aliasing in the conjugate x-f space that must be resolved. When regions in the object containing fast dynamic change are sparse, as in DCE-MRA, signal overlap caused by aliasing is often much less than the undersample factor would imply. x-f Choice reconstruction identifies overlapping signals using a model of the full non-aliased x-f space that is automatically generated from the undersampled data, and applies parallel imaging (PI) to separate them. No extra reference scans are required to generate either the model or the coil sensitivity maps. At each location in the reconstructed images, g-factor noise amplification is compared with predicted reconstruction errors to obtain an optimized solution. Acceleration factors greater than the number of receiver coils are possible, but are limited by the sparseness of the dynamic content and the signal-to-noise ratio (SNR) (in DCE-MRA the latter is dominant). Temporal fidelity was validated for up to a factor 10 speed-up using retrospectively undersampled data from a six-coil array. The method was tested on volunteers using fivefold prospective undersampling. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16897770&query_hl=1 ER - TY - JFULL T1 - Imaging the role of dopamine in health and disease Parkinson's disease as a lesion model. A1 - Brooks, DJ J1 - Wien Klin Wochenschr Y1 - 2006/10// VL - 118 SN - 0043-5325 SP - 570 EP - 572 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17136330&query_hl=1 ER - TY - JFULL T1 - Effect of nutritional counselling on hepatic, muscle and adipose tissue fat content and distribution in non-alcoholic fatty liver disease. A1 - Thomas, EL A1 - Brynes, AE A1 - Hamilton, G A1 - Patel, N A1 - Spong, A A1 - Goldin, RD A1 - Frost, G A1 - Bell, JD A1 - Taylor-Robinson, SD J1 - World J Gastroenterol Y1 - 2006/09/28/ VL - 12 SN - 1007-9327 SP - 5813 EP - 5819 N2 - AIM: To assess the effectiveness of the current UK clinical practice in reducing hepatic fat (IHCL). METHODS: Whole body MRI and (1)H MRS were obtained, before and after 6 mo nutritional counselling, from liver, soleus and tibialis muscles in 10 subjects with non-alcoholic fatty liver disease (NAFLD). RESULTS: A 500 Kcal-restricted diet resulted in an average weight loss of 4% (-3.4 kg,) accompanied by significant reductions in most adipose tissue (AT) depots, including subcutaneous (-9.9%), abdominal subcutaneous (-10.2%) and intra-abdominal-AT (-11.4%). Intramyocellular lipids (IMCL) were significantly reduced in the tibialis muscle (-28.2%). Decreases in both IHCL (-39.9%) and soleus IMCL (-12.2%) content were also observed, although these were not significant. Several individuals showed dramatic decreases in IHCL, while others paradoxically showed increases in IHCL content. Changes in body composition were accompanied by improvements in certain liver function tests: serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Significant correlations were found between decreases in IHCL and reductions in both intra-abdominal and abdominal subcutaneous AT. Improvements in liver function tests were associated with reductions in intra-abdominal AT, but not with changes in IHCL. CONCLUSION: This study shows that even a very modest reduction in body weight achieved through lifestyle modification can result in changes in body fat depots and improvements in LFTs. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17007047&query_hl=1 ER - TY - JFULL T1 - MAGfect: a novel liposome formulation for MRI labelling and visualization of cells. A1 - Oliver, M A1 - Ahmad, A A1 - Kamaly, N A1 - Perouzel, E A1 - Caussin, A A1 - Keller, M A1 - Herlihy, A A1 - Bell, J A1 - Miller, AD A1 - Jorgensen, MR J1 - Org Biomol Chem Y1 - 2006/09/21/ VL - 4 SN - 1477-0520 SP - 3489 EP - 3497 N2 - Cellular entry of imaging probes, such as contrast agents for magnetic resonance imaging (MRI), is a key requirement for many molecular imaging studies, particularly imaging intracellular events and cell tracking. Here, we describe the successful development and in vitro analysis of MAGfect, a novel liposome formulation containing a lipidic gadolinium contrast agent for MRI, Gd-DOTA-Chol , designed to enter and label cells. Liposome formulation and cell incubation time were optimised for maximum cellular uptake of the imaging probe in a variety of cell lines. MRI analysis of cells incubated with MAGfect showed them to be highly MRI active. This formulation was examined further for cytotoxicity, cell viability and mechanism of cell labelling. One of the key advantages of using MAGfect as a labelling vehicle arises from its potential for additional functions, such as concomitant drug or gene delivery and fluorescent labelling. The gadolinium liposome was found to be an effective vehicle for transport of plasmid DNA (pDNA) into cells and expression levels were comparable to the commercial transfection agent Trojene. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17036144&query_hl=1 ER - TY - JFULL T1 - Development of a novel optimized breathhold technique for myocardial T2 measurement in thalassemia. A1 - He, T A1 - Gatehouse, PD A1 - Anderson, LJ A1 - Tanner, M A1 - Keegan, J A1 - Pennell, DJ A1 - Firmin, DN J1 - J Magn Reson Imaging Y1 - 2006/09// VL - 24 SN - 1053-1807 SP - 580 EP - 585 N2 - PURPOSE: To develop a reproducible fast spin-echo (FSE) technique for accurate myocardial T2 measurement with application to iron overload assessment in thalassemia. MATERIALS AND METHODS: An FSE sequence was developed to permit acquisition of multiple TE images in one breathhold (BH-FSE). A dynamic black-blood scheme was introduced to better cancel blood signal. A nonselective refocusing train was also adopted to suppress stimulated echoes. The optimized technique was tested on phantoms and then applied to 10 normal volunteers and 10 thalassemia patients. Interstudy reproducibility was measured on all the 20 subjects. RESULTS: The mean difference in T2 values was 1.7% from phantom experiments between BH-FSE and the conventional spin-echo (SE) technique. High contrast BH-FSE images were acquired from human subjects, with minimal stimulated echoes and effective blood suppression (P = 0.0005). The coefficient of variation for interstudy reproducibility was 4.3%. T2 values from thalassemia patients were substantially lower than those from the normal subjects (45.2 +/- 26.1 msec vs. 56.9 +/- 8.4 ms, P = 0.02). CONCLUSION: The dynamic black-blood T2 sequence is a fast reproducible acquisition that compares favorably with conventional techniques, is robust to motion artifacts, and yields high blood-myocardium contrast. This technique may provide a useful tool in thalassemia and other scenarios requiring myocardial T2 quantification. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16892203&query_hl=1 ER - TY - JFULL T1 - Determinants of adiposity during preweaning postnatal growth in appropriately grown and growth-restricted term infants. A1 - Modi, N A1 - Thomas, EL A1 - Harrington, TA A1 - Uthaya, S A1 - Doré, CJ A1 - Bell, JD J1 - Pediatr Res Y1 - 2006/09// VL - 60 SN - 0031-3998 SP - 345 EP - 348 N2 - The distribution and quantity of adipose tissue are markers of morbidity risk in children and adults. Poor intrauterine growth and accelerated postnatal growth are believed to add to these risks. The aim of this study was to assess adipose tissue content and distribution at birth and 6 wk in relation to intrauterine growth restriction, postnatal growth, and infant diet. We measured weight, length, and head circumference and adipose content and distribution using magnetic resonance imaging at 6 wk of age in appropriately grown for gestational age (AGA) and growth-restricted (GR) infants and compared this with birth data. By 6 wk, GR infants showed complete catch-up in comparison to AGA infants in relation to head growth and adiposity. Catch-up in length and weight was not complete. Accelerated linear growth, but not accelerated weight gain, was associated with a highly significant increase in adiposity (r = 0.57, p = 0.001) regardless of AGA/GR status. The highest adiposity at 6 wk, allowing for baseline variables and linear growth, was seen in exclusively breast-fed GR infants (mean, 95% confidence interval: 33.5%, 29.51-37.5). Adipose tissue distribution remained constant and was unrelated to growth and diet. Reduced birth adiposity (B = -0.185, p = 0.003), but not low birth head size (B = 0.32, p = 0.093), was a significant predictor of accelerated postnatal head growth (R(2) = 0.29, adjusted R(2) = 0.23, p = 0.012). Increasing adiposity appears to be an inevitable accompaniment of accelerated linear growth. Low total adipose tissue quantity at birth appears to direct nutrition toward head growth. Adipose tissue may be involved in the signaling of catch-up growth. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16857778&query_hl=1 ER - TY - JFULL T1 - PET markers of amyloid deposition and inflammation A1 - Brooks, DJ J1 - EUR J NEUROL Y1 - 2006/09// VL - 13 SN - 1351-5101 SP - 305 EP - 305 ER - TY - JFULL T1 - Frequently encountered cranial ultrasound (cUS) features in the preterm infants' brain: Correlation between cUS and MRI A1 - Leijser, LM A1 - Srinivasan, L A1 - Rutherford, MA A1 - Counsell, SJ A1 - Allsop, JM A1 - Cowan, FM J1 - EARLY HUM DEV Y1 - 2006/09// VL - 82 SN - 0378-3782 SP - 632 EP - 632 ER - TY - JFULL T1 - Critical role for peptide YY in protein-mediated satiation and body-weight regulation. A1 - Batterham, RL A1 - Heffron, H A1 - Kapoor, S A1 - Chivers, JE A1 - Chandarana, K A1 - Herzog, H A1 - Le Roux, CW A1 - Thomas, EL A1 - Bell, JD A1 - Withers, DJ J1 - Cell Metab Y1 - 2006/09// VL - 4 SN - 1550-4131 SP - 223 EP - 233 N2 - Dietary protein enhances satiety and promotes weight loss, but the mechanisms by which appetite is affected remain unclear. We investigated the role of gut hormones, key regulators of ingestive behavior, in mediating the satiating effects of different macronutrients. In normal-weight and obese human subjects, high-protein intake induced the greatest release of the anorectic hormone peptide YY (PYY) and the most pronounced satiety. Long-term augmentation of dietary protein in mice increased plasma PYY levels, decreased food intake, and reduced adiposity. To directly determine the role of PYY in mediating the satiating effects of protein, we generated Pyy null mice, which were selectively resistant to the satiating and weight-reducing effects of protein and developed marked obesity that was reversed by exogenous PYY treatment. Our findings suggest that modulating the release of endogenous satiety factors, such as PYY, through alteration of specific diet constituents could provide a rational therapy for obesity. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16950139&query_hl=1 ER - TY - JFULL T1 - Thalamic atrophy in infants with PVL and cerebral visual impairment. A1 - Ricci, D A1 - Anker, S A1 - Cowan, F A1 - Pane, M A1 - Gallini, F A1 - Luciano, R A1 - Donvito, V A1 - Baranello, G A1 - Cesarini, L A1 - Bianco, F A1 - Rutherford, M A1 - Romagnoli, C A1 - Atkinson, J A1 - Braddick, O A1 - Guzzetta, F A1 - Mercuri, E J1 - Early Hum Dev Y1 - 2006/09// VL - 82 SN - 0378-3782 SP - 591 EP - 595 N2 - The aim of this retrospective study was to establish the presence and severity of cerebral visual impairment in preterm infants with PVL. We also wished to establish whether abnormalities of visual function are related to brain MRI findings and more specifically not only to the involvement of optic radiations and occipital cortex but also to changes in the thalami, that are often affected in infants with PVL. Twelve infants with cystic PVL were assessed at 1 year (+2) corrected age with a battery of tests specifically designed to assess various aspects of visual function in infancy, such as ocular movements, visual acuity, visual fields and fixation shift. All infants also had a brain MRI. Eleven of the 12 had involvement of the optic radiations: all had some abnormalities of visual function and visual impairment was more severe in infants with more extensive involvement of the optic radiations. The child with normal optic radiations had normal visual function. Six of the 12 infants also had obvious signs of atrophy of the thalami and all had severe and wide-ranging abnormalities of visual function in all testing domains. Two children had equivocal atrophy of the thalami, both had some abnormalities of visual function. Four children had normal thalami and had normal visual function or only minor abnormalities on one of the visual tests. Our results suggest that the atrophy of the thalami may play an additional role in the abnormal development of visual function in infants with PVL and abnormal optic radiations. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16500047&query_hl=1 ER - TY - JFULL T1 - Patterns of brain injury seen in neonates presenting with a postnatal collapse A1 - Foran, A A1 - Rutherford, M A1 - Cowan, F J1 - EARLY HUM DEV Y1 - 2006/09// VL - 82 SN - 0378-3782 SP - 629 EP - 629 ER - TY - JFULL T1 - Aspirin-treated human DCs up-regulate ILT-3 and induce hyporesponsiveness and regulatory activity in responder T cells A1 - Buckland, M A1 - Jago, CB A1 - Fazekasova, H A1 - Scott, K A1 - Tan, PH A1 - George, AJT A1 - Lechler, R A1 - Lombardi, G J1 - AM J TRANSPLANT Y1 - 2006/09// VL - 6 SN - 1600-6135 SP - 2046 EP - 2059 N2 - Mature dendritic cells (mDCs) are potent antigen presenting cells, but immature DCs (iDCs) have been shown to have reduced antigen stimulatory capacity. Different strategies have been investigated to augment the tolerogenic capacity of dendritic cells (DCs). We demonstrate that in aspirin-treated human DCs, there is reduced expression of CD1a, HLA-DR and CD86, up-regulation of ILT-3 expression and marginal increases in PDL-1. Aspirin-treated DCs are partially resistant to phenotypic changes following maturational stimuli, such as lipopolysaccharide (LPS) or TNF alpha, IL-1 alpha and PGE(2). Aspirin-treated DCs demonstrate normal endocytic function, but have a reduced ability to stimulate allogeneic T cells, which is comparable to iDCs. Furthermore, they induce hyporesponsiveness and regulatory activity in responder naive and memory T cells; for naive T cells this is achieved more quickly and efficiently than with iDCs. We investigated the mechanism of this regulatory activity and found that both cell-cell contact and inhibitory cytokine activity are involved, although no one cytokine predominates in importance. Blocking ILT-3 or IL-12 does not diminish the capacity of these DCs to induce regulation or Foxp3 expression on the regulatory T cells. Results demonstrate that aspirin-treated DCs display tolerogenic potential, which is of interest in their therapeutic potential in reducing chronic allograft rejection. ER - TY - JFULL T1 - Neurological outcome of premature infants following a controlled-trial of skin-to-skin contact A1 - Hickson, A A1 - Rutherford, M A1 - Glover, V A1 - Stevenson, J A1 - Dore, C A1 - Cowan, F A1 - Modi, N J1 - EARLY HUM DEV Y1 - 2006/09// VL - 82 SN - 0378-3782 SP - 631 EP - 632 ER - TY - JFULL T1 - The effect of preterm birth on neonatal cerebral vasculature studied with magnetic resonance angiography at 3 Tesla. A1 - Malamateniou, C A1 - Counsell, SJ A1 - Allsop, JM A1 - Fitzpatrick, JA A1 - Srinivasan, L A1 - Cowan, FM A1 - Hajnal, JV A1 - Rutherford, MA J1 - Neuroimage Y1 - 2006/09// VL - 32 SN - 1053-8119 SP - 1050 EP - 1059 N2 - Preterm birth is associated with a high incidence of neurodevelopmental deficits. Magnetic resonance imaging (MRI) has proved to be a valuable tool for monitoring development in the preterm brain. We used a dedicated time-of-flight (TOF) magnetic resonance angiography (MRA) protocol at 3 Tesla (3T) optimized to assess morphological characteristics of the neonatal cerebral vessels associated with preterm birth in a sample of 37 infants. We found statistically significant decreased tortuosity in all proximal segments of the cerebral vasculature (anterior, middle and posterior cerebral arteries) in the preterm infants imaged at term equivalent age compared to the term born infants, with no differences in vessel diameter between the two groups. This distinct phenotype of decreased tortuosity was shown to persist until 18 months of age in longitudinal MRA studies in infants born preterm, suggesting that this is not a delay in maturation. Biparietal head diameter measurements were significantly smaller in the preterm at term infants and were inversely correlated with middle cerebral artery tortuosity measurements in both the term born and the preterm at term infants. To our knowledge, this is the first systematic MRA study on the effect of preterm delivery on neonatal cerebral vasculature. Our intention is to build on the findings of this study by combining the data with other measurements of brain growth and vascular haemodynamics to understand more about the interdependence of vessel and brain development and their relationship to prematurity. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16860576&query_hl=1 ER - TY - JFULL T1 - Current and future applications of in vitro magnetic resonance spectroscopy in hepatobiliary disease. A1 - Cox, IJ A1 - Sharif, A A1 - Cobbold, JF A1 - Thomas, HC A1 - Taylor-Robinson, SD J1 - World J Gastroenterol Y1 - 2006/08/14/ VL - 12 SN - 1007-9327 SP - 4773 EP - 4783 N2 - Nuclear magnetic resonance spectroscopy allows the study of cellular biochemistry and metabolism, both in the whole body in vivo and at higher magnetic field strengths in vitro. Since the technique is non-invasive and non-selective, magnetic resonance spectroscopy methodologies have been widely applied in biochemistry and medicine. In vitro magnetic resonance spectroscopy studies of cells, body fluids and tissues have been used in medical biochemistry to investigate pathophysiological processes and more recently, the technique has been used by physicians to determine disease abnormalities in vivo. This highlighted topic illustrates the potential of in vitro magnetic resonance spectroscopy in studying the hepatobiliary system. The role of in vitro proton and phosphorus magnetic resonance spectroscopy in the study of malignant and non-malignant liver disease and bile composition studies are discussed, particularly with reference to correlative in vivo whole-body magnetic resonance spectroscopy applications. In summary, magnetic resonance spectroscopy techniques can provide non-invasive biochemical information on disease severity and pointers to underlying pathophysiological processes. Magnetic resonance spectroscopy holds potential promise as a screening tool for disease biomarkers, as well as assessing therapeutic response. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16937457&query_hl=1 ER - TY - JFULL T1 - Current and future applications of in vitro magnetic resonance spectroscopy in hepatobiliary disease A1 - Cox, IJ A1 - Sharif, A A1 - Cobbold, JFL A1 - Thomas, HC A1 - Taylor-Robinson, SD J1 - WORLD J GASTROENTERO Y1 - 2006/08/14/ VL - 12 SN - 1007-9327 SP - 4773 EP - 4783 N2 -

Nuclear magnetic resonance spectroscopy allows the study of cellular biochemistry and metabolism, both in the whole body in vivo and at higher magnetic field strengths in vitro. Since the technique is non-invasive and non-selective, magnetic resonance spectroscopy methodologies have been widely applied in biochemistry and medicine. In vitro magnetic resonance spectroscopy studies of cells, body fluids and tissues have been used in medical biochemistry to investigate pathophysiological processes and more recently, the technique has been used by physicians to determine disease abnormalities in vivo. This highlighted topic illustrates the potential of in vitro magnetic resonance spectroscopy in studying the hepatobiliary system. The role of in vitro proton and phosphorus magnetic resonance spectroscopy in the study of malignant and non-malignant liver disease and bile composition studies are discussed, particularly with reference to correlative in vivo whole-body magnetic resonance spectroscopy applications. In summary, magnetic resonance spectroscopy techniques can provide non-invasive biochemical information on disease severity and pointers to underlying pathophysiological processes. Magnetic resonance spectroscopy holds potential promise as a screening tool for disease biomarkers, as well as assessing therapeutic response. (C) 2006 The WIG Press. All rights reserved.

ER - TY - JFULL T1 - Neurocognitive findings in Prader-Willi syndrome and early-onset morbid obesity. A1 - Miller, J A1 - Kranzler, J A1 - Liu, Y A1 - Schmalfuss, I A1 - Theriaque, DW A1 - Shuster, JJ A1 - Hatfield, A A1 - Mueller, OT A1 - Goldstone, AP A1 - Sahoo, T A1 - Beaudet, AL A1 - Driscoll, DJ J1 - J Pediatr Y1 - 2006/08// VL - 149 SN - 0022-3476 SP - 192 EP - 198 N2 - OBJECTIVES: To examine whether early-onset morbid obesity is associated with cognitive impairment, neuropathologic changes, and behavioral problems. STUDY DESIGN: This case-control study compared head MRI scans and cognitive, achievement, and behavioral evaluations of subjects with Prader-Willi syndrome (PWS), early-onset morbid obesity (EMO), and normal-weight sibling control subjects from both groups. Head MRI was done on 17 PWS, 18 EMO, and 21 siblings, and cognitive, achievement, and behavioral evaluations were done on 19 PWS, 17 EMO, and 24 siblings. RESULTS: The mean General Intellectual Ability score of the EMO group was 77.4 +/- 17.8; PWS, 63.3 +/- 14.2; and control subjects, 106.4 +/- 13.0. Achievement scores for the three groups were EMO, 78.7 +/- 18.8; PWS, 71.2 +/- 17.0; and control subjects, 104.8 +/- 17.0. Significant negative behaviors and poor adaptive skills were found in the EMO group. White matter lesions were noted on brain MRI in 6 subjects with PWS and 5 with EMO. None of the normal-weight control subjects had these findings. CONCLUSIONS: Individuals with EMO have significantly lower cognitive function and more behavioral problems than control subjects with no history of childhood obesity. Both EMO and PWS subjects have white matter lesions on brain MRI that have not previously been described. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16887432&query_hl=1 ER - TY - JFULL T1 - Differential effects of costimulatory pathway modulation on corneal allograft survival. A1 - Watson, MP A1 - George, AJ A1 - Larkin, DF J1 - Invest Ophthalmol Vis Sci Y1 - 2006/08// VL - 47 SN - 0146-0404 SP - 3417 EP - 3422 N2 - PURPOSE: T lymphocytes have a central role in allograft rejection. On engagement of the T cell receptor by antigenic peptide-major histocompatibility complex (MHC) complex, a second "costimulatory" signal is critical to full T-cell activation or downregulation. In this study, the effect on corneal allograft survival of modulation of the costimulatory molecules programmed death-1 (PD-1) and inducible costimulatory (ICOS) molecule was examined. These molecules are known to modulate, respectively, negative or positive T-cell activation signals. METHODS: A dimeric PD-L1 immunoglobulin (Ig) fusion protein was generated to stimulate the inhibitory receptor PD-1, and a monoclonal antibody was used to block ICOS. The effect of PD-1 engagement and ICOS blockade on lymphocyte activation by in vitro T-cell proliferation and the effect on orthotopic corneal allograft survival in BALB/c mice were determined. RESULTS: Both reagents demonstrated T-cell inhibition in vitro. PD-L1.Ig treatment of BALB/c mice prolonged fully MHC-mismatched C3H donor corneal allograft survival, with a median survival time (MST) of 21 days. This was significantly prolonged compared to isotype control protein-treated recipients (MST 13 days, P < 0.003). Allograft survival in BALB/c recipients treated with anti-ICOS antibody showed no prolongation of survival compared with the isotype control antibody (MST, 12 days in both groups). CONCLUSIONS: Augmented ligation of the PD-1 negative costimulatory molecule significantly prolongs corneal allograft survival. However, in contrast to findings in other allograft models, signaling through the positive costimulatory molecule ICOS appears to be less important in allogeneic rejection of cornea. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16877411&query_hl=1 ER - TY - JFULL T1 - Abnormal cortical development after premature birth shown by altered allometric scaling of brain growth. A1 - Kapellou, O A1 - Counsell, SJ A1 - Kennea, N A1 - Dyet, L A1 - Saeed, N A1 - Stark, J A1 - Maalouf, E A1 - Duggan, P A1 - Ajayi-Obe, M A1 - Hajnal, J A1 - Allsop, JM A1 - Boardman, J A1 - Rutherford, MA A1 - Cowan, F A1 - Edwards, AD J1 - PLoS Med Y1 - 2006/08// VL - 3 SN - 1549-1676 SP - e265 EP - e265 N2 - BACKGROUND: We postulated that during ontogenesis cortical surface area and cerebral volume are related by a scaling law whose exponent gives a quantitative measure of cortical development. We used this approach to investigate the hypothesis that premature termination of the intrauterine environment by preterm birth reduces cortical development in a dose-dependent manner, providing a neural substrate for functional impairment. METHODS AND FINDINGS: We analyzed 274 magnetic resonance images that recorded brain growth from 23 to 48 wk of gestation in 113 extremely preterm infants born at 22 to 29 wk of gestation, 63 of whom underwent neurodevelopmental assessment at a median age of 2 y. Cortical surface area was related to cerebral volume by a scaling law with an exponent of 1.29 (95% confidence interval, 1.25-1.33), which was proportional to later neurodevelopmental impairment. Increasing prematurity and male gender were associated with a lower scaling exponent (p < 0.0001) independent of intrauterine or postnatal somatic growth. CONCLUSIONS: Human brain growth obeys an allometric scaling relation that is disrupted by preterm birth in a dose-dependent, sexually dimorphic fashion that directly parallels the incidence of neurodevelopmental impairments in preterm infants. This result focuses attention on brain growth and cortical development during the weeks following preterm delivery as a neural substrate for neurodevelopmental impairment after premature delivery. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16866579&query_hl=1 ER - TY - JFULL T1 - Prenatal diagnosis of absent right and persistent left superior vena cava A1 - Pasquini, L A1 - Belmar, C A1 - Seale, A A1 - Gardiner, HM J1 - PRENATAL DIAG Y1 - 2006/08// VL - 26 SN - 0197-3851 SP - 700 EP - 702 N2 - Objective Persistence of left superior vena cava (LSVC) is a known variant of the systemic venous return. In the setting of an otherwise structurally normal heart, absence of the right superior vena cava (RSVC) but persistence of the LSVC is rare.Methods We describe the prenatal findings of a fetus with absent right and persistent LSVC.Results A dichorionic diamniotic twin pregnancy was referred to our centre with cardiac disproportion. Twin A had disproportion at four-chamber level, an absent right but persistent LSVC draining to an enlarged coronary sinus and a hypoplastic transverse aortic arch (< 2 mm). Postnatal echocardiography of the asymptomatic baby confirmed the prenatal diagnosis, and serial echocardiograms demonstrated general hypoplasia of the aortic arch but no discrete coarctation (CoA). No intervention was required and the baby is thriving aged 10 months.Conclusion Persistence of LSVC is a known variant of the systemic venous return. In the setting of an otherwise structurally normal heart, absence of the right but persistence of LSVC is rare. Copyright (c) 2006 John Wiley & Sons, Ltd. ER - TY - JFULL T1 - Role of alloantibodies in the pathogenesis of graft arteriosclerosis in cardiac transplantation. A1 - Soleimani, B A1 - Lechler, RI A1 - Hornick, PI A1 - George, AJ J1 - Am J Transplant Y1 - 2006/08// VL - 6 SN - 1600-6135 SP - 1781 EP - 1785 N2 - Graft arteriosclerosis (GA) remains the leading obstacle to long-term survival of cardiac allografts. The pathogenesis of this chronic disease, though perceived to be multifactorial, is most likely immune-driven. Based on clinical and experimental observations, the humoral arm of the immune system has long been suspected to play a pivotal role in the disease process. In this article, we shall review the evidence generated from key clinical and experimental studies on the role of alloantibodies in GA. We will argue that although the strong correlation between the presence of anti-donor antibodies in clinical and experimental GA is highly suggestive of a pathogenic role for alloantibodies, a direct causal link between GA and the humoral arm of the alloresponse cannot yet be established based on the currently available evidence, and may in fact be one of a number of pathogenic processes that potentiate this vasculopathy. Finally, in this article, we shall discuss some of the potential mechanisms by which alloantibodies may exert their pathogenic effect in GA. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16771817&query_hl=1 ER - TY - JFULL T1 - Gene Therapy for Clinical Transplantation: Where Do We Stand in 2006? A1 - Tan, PH A1 - George, AJ A1 - Handa, AI J1 - Discov Med Y1 - 2006/08// VL - 6 SN - 1539-6509 SP - 153 EP - 156 N2 - Gene therapy holds a great promise to prevent allograft rejection or to induce transplant tolerance. Many achievements in vector development have allowed the progression of this therapy to become more attainable in clinical transplantation. In this articles, the authors examine the exciting development in various vector technologies that allows this form of therapy to take the central stage of clinical transplantation. Also highlighted are various therapeutic strategies that might ultimately result in the realization of gene-based treatment in clinical transplantation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17234136&query_hl=1 ER - TY - JFULL T1 - Natural history of brain lesions in extremely preterm infants studied with serial magnetic resonance imaging from birth and neurodevelopmental assessment. A1 - Dyet, LE A1 - Kennea, N A1 - Counsell, SJ A1 - Maalouf, EF A1 - Ajayi-Obe, M A1 - Duggan, PJ A1 - Harrison, M A1 - Allsop, JM A1 - Hajnal, J A1 - Herlihy, AH A1 - Edwards, B A1 - Laroche, S A1 - Cowan, FM A1 - Rutherford, MA A1 - Edwards, AD J1 - Pediatrics Y1 - 2006/08// VL - 118 SN - 1098-4275 SP - 536 EP - 548 N2 - OBJECTIVES: The aim was to survey the range of cerebral injury and abnormalities of cerebral development in infants born between 23 and 30 weeks' gestation using serial MRI scans of the brain from birth, and to correlate those findings with neurodevelopmental outcome after 18 months corrected age. METHODS: Between January 1997 and November 2000, consecutive infants born at < 30 weeks' gestational age underwent serial MRI brain scans from birth until term-equivalent age. Infants were monitored after 18 months of age, corrected for prematurity, with the Griffiths Mental Development Scales and neurologic assessment. RESULTS: A total of 327 MRI scans were obtained from 119 surviving infants born at 23 to 30 weeks of gestation. Four infants had major destructive brain lesions, and tissue loss was seen at term for the 2 survivors. Fifty-one infants had early hemorrhage; 50% of infants with term scans after intraventricular hemorrhage had ventricular dilation. Twenty-six infants had punctate white matter lesions on early scans; these persisted for 33% of infants assessed at term. Early scans showed cerebellar hemorrhagic lesions for 8 infants and basal ganglia abnormalities for 17. At term, 53% of infants without previous hemorrhage had ventricular dilation and 80% of infants had diffuse excessive high signal intensity within the white matter on T2-weighted scans. Complete follow-up data were available for 66% of infants. Adverse outcomes were associated with major destructive lesions, diffuse excessive high signal intensity within the white matter, cerebellar hemorrhage, and ventricular dilation after intraventricular hemorrhage but not with punctate white matter lesions, hemorrhage, or ventricular dilation without intraventricular hemorrhage. CONCLUSIONS: Diffuse white matter abnormalities and post-hemorrhagic ventricular dilation are common at term and seem to correlate with reduced developmental quotients. Early lesions, except for cerebellar hemorrhage and major destructive lesions, do not show clear relationships with outcomes. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16882805&query_hl=1 ER - TY - JFULL T1 - Neurological examination at 6 to 9 months in infants with cystic periventricular leukomalacia. A1 - Ricci, D A1 - Cowan, F A1 - Pane, M A1 - Gallini, F A1 - Haataja, L A1 - Luciano, R A1 - Cesarini, L A1 - Leone, D A1 - Donvito, V A1 - Baranello, G A1 - Rutherford, M A1 - Romagnoli, C A1 - Dubowitz, L A1 - Mercuri, E J1 - Neuropediatrics Y1 - 2006/08// VL - 37 SN - 0174-304X SP - 247 EP - 252 N2 - The Hammersmith Infant Neurological Examination was performed in 24 infants with cystic periventricular leukomalacia whose gestational age ranged between 26-38 weeks. The infants were examined between 6 and 9.5 months corrected age. The aim of the study was to establish the different patterns of neurological abnormality as well as the optimality scores that predict the severity of motor sequelae at 2 years. Increased neck and trunk extensor tone, and a posture of flexed arms and extended legs between 6 and 9 months were always associated with the inability to sit unsupported at 2 years, whilst truncal hypotonia and extended arms and legs were associated with unsupported sitting but not walking. Optimality scores between 41 and 60 were generally associated with sitting but not walking at 2 years whilst scores below 40 were always associated with the inability to sit independently at 2 years. All infants who did not develop cerebral palsy at 2 years had scores > 60. Our results suggest that the pattern of findings on neurological examination performed between 6 and 9 months as well as the calculated optimality score helps to predict motor impairment in infants with PVL. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17177152&query_hl=1 ER - TY - JFULL T1 - Dopaminergic action beyond its effects on motor function: Imaging studies. A1 - Brooks, DJ J1 - J Neurol Y1 - 2006/08// VL - 253 Suppl 4 SN - 0340-5354 SP - iv8 EP - iv15 N2 - Along with motor programming, it is now thought that tonic release of dopamine in the striatum acts to focus and filter non-motor activities such as working memory, implicit learning, decision making, and planning. Additionally, thresholds to painful stimuli may well be dopamine dependant. Phasic (burst) release of dopamine in the basal ganglia and frontal areas is thought to play a role in alerting organisms to novel and potentially rewarding stimuli and in mediating contextual learning. Dopamine release also drives a craving for stimuli and facilitates their enjoyment.Functional imaging can help elucidate the role of dopamine in mediating non-motor activities. The integrity of dopamine terminal function can be measured with PET and SPECT in vivo in health and Parkinson's disease (PD) and this can be correlated with performance of executive tasks. In addition, these imaging modalities allow dopamine release in response to stimuli (both rewarding and unrewarding) to be detected, as reflected by changes in D2 receptor availability to radioligands. Finally, the functional effects of dopamine deficiency and its replacement can be monitored by studying patterns of brain activation, as evidenced by regional blood flow changes. In this review, some of the insights that imaging has given us concerning the role of dopamine in non-motor functions is presented. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16944357&query_hl=1 ER - TY - JFULL T1 - Cardiovascular magnetic resonance measurement of peak aortic velocities before and after aortic valve replacement in patients with severe aortic stenosis: randomised comparison of stentless vs. stened A1 - De Arenaza, DP A1 - Kilner, P A1 - Flather, MD A1 - Lees, B A1 - Prasad, S A1 - Jasinski, M A1 - Pennell, D A1 - Pepper, J A1 - Assert Inves J1 - EUR HEART J Y1 - 2006/08// VL - 27 SN - 0195-668X SP - 419 EP - 420 ER - TY - JFULL T1 - Prognostic value of cardiovascular magnetic resonance assessment of LV function and scar - a multicenter study A1 - Klem, I A1 - Shah, DJ A1 - White, RD A1 - Pennell, D A1 - Van Rossum, AC A1 - Regenfus, M A1 - Sechtem, U A1 - Schvartzman, P A1 - Siemens Res Collaborative Grp J1 - EUR HEART J Y1 - 2006/08// VL - 27 SN - 0195-668X SP - 28 EP - 28 ER - TY - JFULL T1 - Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 cause Aicardi-Goutières syndrome at the AGS1 locus. A1 - Crow, YJ A1 - Hayward, BE A1 - Parmar, R A1 - Robins, P A1 - Leitch, A A1 - Ali, M A1 - Black, DN A1 - van Bokhoven, H A1 - Brunner, HG A1 - Hamel, BC A1 - Corry, PC A1 - Cowan, FM A1 - Frints, SG A1 - Klepper, J A1 - Livingston, JH A1 - Lynch, SA A1 - Massey, RF A1 - Meritet, JF A1 - Michaud, JL A1 - Ponsot, G A1 - Voit, T A1 - Lebon, P A1 - Bonthron, DT A1 - Jackson, AP A1 - Barnes, DE A1 - Lindahl, T J1 - Nat Genet Y1 - 2006/08// VL - 38 SN - 1061-4036 SP - 917 EP - 920 N2 - Aicardi-Goutières syndrome (AGS) presents as a severe neurological brain disease and is a genetic mimic of the sequelae of transplacentally acquired viral infection. Evidence exists for a perturbation of innate immunity as a primary pathogenic event in the disease phenotype. Here, we show that TREX1, encoding the major mammalian 3' --> 5' DNA exonuclease, is the AGS1 gene, and AGS-causing mutations result in abrogation of TREX1 enzyme activity. Similar loss of function in the Trex1(-/-) mouse leads to an inflammatory phenotype. Our findings suggest an unanticipated role for TREX1 in processing or clearing anomalous DNA structures, failure of which results in the triggering of an abnormal innate immune response. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16845398&query_hl=1 ER - TY - JFULL T1 - Proton MR spectroscopy in neonates with perinatal cerebral hypoxic-ischemic injury: Metabolite peak-area ratios, relaxation times, and absolute concentrations A1 - Cheong, JLY A1 - Cady, EB A1 - Penrice, J A1 - Wyatt, JS A1 - Cox, IJ A1 - Robertson, NJ J1 - AM J NEURORADIOL Y1 - 2006/08// VL - 27 SN - 0195-6108 SP - 1546 EP - 1554 N2 - BACKGROUND: Results from cerebral proton H-1-MR spectroscopy studies of neonates with perinatal hypoxic-ischemic injury have generally been presented as metabolite peak-area ratios, which are T1 and T2-weighted, rather than absolute metabolite concentrations. We hypothesized that compared with 1H-MR spectroscopy peak-area ratios, calculation of absolute metabolite concentrations and relaxation times measured within the first 4 days after birth (1) would improve prognostic accuracy and (2) enhance the understanding of underlying neurochemical changes in neonates with neonatal encephalopathy.METHODS: Seventeen term infants with neonatal encephalopathy and 10 healthy controls were studied at 2.4T at 1 (1-3) and 2 (2-4) (median [interquartile range]) days afterbirth, respectively. Infants with neonatal encephalopathy were classified into 2 outcome groups (normal/mild and severe/fatal), according to neurodevelopmental assessments at 1 year. The MR spectroscopy peak-area ratios, relaxation times, absolute concentrations, and concentration ratios of lactate (Lac), creatine plus phosphocreatine (Cr), N-acetylaspartate (NAA), and choline-containing compounds (Cho) from a voxel centered on the thalami were analyzed according to outcome group.RESULTS: Comparing the severe/fatal group with the controls (significance assumed with P < 0.05), we found that Lac/NAA, Lac/Cho, and Lac/Cr peak-area ratios increased and NAA/Cr and NAA/Cho decreased; Lac, NAA, and Cr T2s were increased; [Lac] was increased and [Cho], [Cr], and [NAA] decreased; and among the concentration ratios, only [Lac]/[NAA] was increased. Comparison of the normal/mild group with controls revealed no differences in peak-area ratios, relaxation times, or concentration ratios but decreased [NAA], [Cho], and [Cr] were observed in the infants with normal/mild outcome. Comparison of the normal/mild and severe/fatal groups showed increased Lac/NAA and Lac/Cho and decreased NAA/Cr and NAA/Cho peak-area ratios, reduced [NAA], and increased Lac T2 in the infants with the worse outcome.CONCLUSIONS: Metabolite concentrations, in particular [NAA], enhance the prognostic accuracy of cerebral H-1-MR spectroscopy-[NAA] was the only measurable to discriminate among all (control, normal/mild, and severe/fatal outcome) groups. However, peak-area ratios are more useful prognostic indicators than concentration ratios because they depend on metabolite concentrations and T2s, both of which are pathologically modulated. Concentration ratios depend only on the concentrations of the constituent metabolites. Increased Cr T2 may provide an indirect marker of impaired cellular energetics, and similarly, NAA T2 may constitute an index of exclusively neuronal energy status. Our recommendation is to collect data that enable calculation of brain metabolite concentrations. However, if time constraints make this impossible, metabolite peak-area ratios provide the next best method of assigning early prognosis in neonatal encephalopathy. ER - TY - JFULL T1 - Increased periconceptual maternal glycated haemoglobin in diabetic mothers reduces fetal long axis cardiac function. A1 - Gardiner, HM A1 - Pasquini, L A1 - Wolfenden, J A1 - Kulinskaya, E A1 - Li, W A1 - Henein, M J1 - Heart Y1 - 2006/08// VL - 92 SN - 1468-201X SP - 1125 EP - 1130 N2 - OBJECTIVE: To compare ventricular long axis function in fetuses of diabetic mothers (FDM) with contemporaneously studied normal controls (N) and to assess the effect of pre-pregnancy diabetic control on these measurements. DESIGN: Long axis function was compared in 41 FDM and 159 N fetuses in a cross sectional observational study. SETTING: Fetal medicine unit. METHODS AND RESULTS: Echocardiography confirmed structural normality. Pulsed wave valvar Doppler velocimetry, lengthening and shortening myocardial velocities, and amplitude of ventricular long axis movement were recorded at the base of the left and right ventricular free walls and septum. Periconceptual diabetic control was assessed by haemoglobin A1c (HbA1c) in early pregnancy. Doppler and myocardial velocities were negatively related and myocardial thickness was positively related with HbA1c. In both cohorts all variables except mitral and tricuspid late filling (A wave) velocities were dependent on gestational age. FDM gestational age related values were higher for most variables and robust analysis of covariance showed significantly different maturation patterns in mitral valve E:A ratio (p = 0.036) and pulmonary velocity (p = 0.04), late lengthening myocardial velocities (left p = 0.016 and right p = 0.066), left myocardial shortening velocities (p = 0.008), and left free wall (p = 0.03) and septal (p = 0.04) amplitude of motion. FDM septal thickness was significantly increased throughout gestation (p < 0.0001). CONCLUSION: Periconceptual diabetic control influences fetal cardiac performance and myocardial hypertrophy but, unlike the pathophysiology of adult ventricular hypertrophy, is accompanied by functional adaptation. It is unlikely to explain the increased rate of late stillbirth observed in diabetic pregnancies. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16278273&query_hl=1 ER - TY - JFULL T1 - Accuracy of contrast echocardiography for the assessment of left ventricular remodeling compared to gated SPECT following acute myocardial infarction: comparison with magnetic resonance imaging A1 - Lim, TK A1 - Burden, L A1 - Janardhanan, R A1 - Dwivedi, G A1 - Chai, P A1 - Moon, J A1 - Pennell, DJ A1 - Senior, R J1 - EUR HEART J Y1 - 2006/08// VL - 27 SN - 0195-668X SP - 703 EP - 703 ER - TY - JFULL T1 - Gene therapy for transplantation with viral vectors--how much of the promise has been realised? A1 - Tan, PH A1 - Tan, PL A1 - George, AJ A1 - Chan, CL J1 - Expert Opin Biol Ther Y1 - 2006/08// VL - 6 SN - 1744-7682 SP - 759 EP - 772 N2 - Gene therapy holds promise in preventing the development of many diseases. One of the possible applications is the management of organ transplantation. Over the years, advances in vector development have allowed the clinical progression of this form of therapy to become more attainable. Viral vector technology has proved to be better than non-viral vectors at ferrying therapeutic genes to cells. However, many deficiencies in viral vectors hinder the full realisation of gene-based therapy in transplantation. Here, these deficiencies and their ramifications for the future of viral vector development are fully analysed. The authors propose that the slow progress of gene therapy in transplantation may be related to the deficiencies in viral vectors. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16856798&query_hl=1 ER - TY - JFULL T1 - Left ventricular mass regression after aortic valve replacement measured by magnetic resonance: a randomised comparison of stentless vs. stented valves for aortic stenosis A1 - De Arenaza, DP A1 - Flather, MD A1 - Lees, B A1 - Prasad, S A1 - John, A A1 - Cannell, T A1 - Pennell, D A1 - Pepper, J A1 - ASSERT Inves J1 - EUR HEART J Y1 - 2006/08// VL - 27 SN - 0195-668X SP - 421 EP - 422 ER - TY - JFULL T1 - Abnormal deep grey matter development following preterm birth detected using deformation-based morphometry. A1 - Boardman, JP A1 - Counsell, SJ A1 - Rueckert, D A1 - Kapellou, O A1 - Bhatia, KK A1 - Aljabar, P A1 - Hajnal, J A1 - Allsop, JM A1 - Rutherford, MA A1 - Edwards, AD J1 - Neuroimage Y1 - 2006/08/01/ VL - 32 SN - 1053-8119 SP - 70 EP - 78 N2 - Preterm birth is a leading risk factor for neurodevelopmental and cognitive impairment in childhood and adolescence. The most common known cerebral abnormality among preterm infants at term equivalent age is a diffuse white matter abnormality seen on magnetic resonance (MR) images. It occurs with a similar prevalence to subsequent impairment, but its effect on developing neural systems is unknown. MR images were obtained at term equivalent age from 62 infants born at 24-33 completed weeks gestation and 12 term born controls. Tissue damage was quantified using diffusion-weighted imaging, and deformation-based morphometry was used to make a non-subjective survey of the whole brain to identify significant cerebral morphological alterations associated with preterm birth and with diffuse white matter injury. Preterm infants at term equivalent age had reduced thalamic and lentiform volumes without evidence of acute injury in these regions (t = 5.81, P < 0.05), and these alterations were more marked with increasing prematurity (t = 7.13, P < 0.05 for infants born at less than 28 weeks) and in infants with diffuse white matter injury (t = 6.43, P < 0.05). The identification of deep grey matter growth failure in association with diffuse white matter injury suggests that white matter injury is not an isolated phenomenon, but rather, it is associated with the maldevelopment of remote structures. This could be mediated by a disturbance to corticothalamic connectivity during a critical period in cerebral development. Deformation-based morphometry is a powerful tool for modelling the developing brain in health and disease, and can be used to test putative aetiological factors for injury. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16675269&query_hl=1 ER - TY - JFULL T1 - A rapid method for labelling CD4+ T cells with ultrasmall paramagnetic iron oxide nanoparticles for magnetic resonance imaging that preserves proliferative, regulatory and migratory behaviour in vitro. A1 - Garden, OA A1 - Reynolds, PR A1 - Yates, J A1 - Larkman, DJ A1 - Marelli-Berg, FM A1 - Haskard, DO A1 - Edwards, AD A1 - George, AJ J1 - J Immunol Methods Y1 - 2006/07/31/ VL - 314 SN - 0022-1759 SP - 123 EP - 133 N2 - A number of techniques have been developed to track the migration of T cells in vivo, but they all suffer significant shortcomings, including the examination of selected organs rather than the organism as a whole--thus precluding longitudinal studies--or limitations imposed by poor spatial resolution and the application of ionizing radiation. By conjugating the HIV tat peptide to ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles in a reaction yielding a mean valence of 45, a magnetic resonance (MR) contrast agent was synthesised that allowed T cells to be efficiently labelled within just 5 min. The USPIO nanoparticles were incorporated into both the cytoplasm and nucleus of labelled cells, which retained normal in vitro proliferative responses to a polyclonal stimulus; suppressive responses mediated by labelled CD4(+) CD25(+) regulatory T cells; chemotactic responses to the chemokine CXCL-12; and transmigration of an activated endothelial monolayer. We believe that this rapid, efficient and essentially non-toxic approach to labelling both murine and human T cells for MRI holds considerable promise, paving the way for the wider immunological application of this exciting technology. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16860821&query_hl=1 ER - TY - JFULL T1 - Gene delivery by dendrimers operates via different pathways in different cells, but is enhanced by the presence of caveolin. A1 - Manunta, M A1 - Nichols, BJ A1 - Tan, PH A1 - Sagoo, P A1 - Harper, J A1 - George, AJ J1 - J Immunol Methods Y1 - 2006/07/31/ VL - 314 SN - 0022-1759 SP - 134 EP - 146 N2 - In order to optimise and improve the efficacy of transfection mediated by dendrimers, it is essential to fully understand the mechanisms of cell entry and intracellular trafficking by these complexes. Previously, we have shown that gene delivery by dendrimers is dependent from cholesterol and membrane rafts. The inhibition of transfection by treatment with filipin III suggested that gene delivery might be occurring by a caveolin-dependent pathway. We therefore investigated the internalisation and transfection properties of dendriplexes using cell lines (HeLa and HepG2) that express few caveolae. We show that, in contrast to other cells, cholesterol depletion does not affect the ability of dendriplexes to transfect these cells. Inhibition of clathrin-independent, phagocytic and macropinocytic pathways also failed to inhibit transfection of these cells and endothelial cells. However, overexpression of caveolin 1 resulted in an increased rate of dendriplex uptake into HeLa, HepG2 and endothelial cells, and increased transfection efficiency. Furthermore, in endothelial cells, confocal microscopy demonstrated colocalisation of dendriplexes and caveolin 1. These data highlight that dendriplexes may use different internalisation pathways in different cells, and that caveolae form a preferential route for gene delivery by this non-viral vector. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16893551&query_hl=1 ER - TY - JFULL T1 - A sculptural approach to the heart (Science in Society). A1 - Kilner PJ J1 - Nature Y1 - 2006/07/05/ VL - 442 PB - Nature Publishing Group SP - 28 EP - 29 UR - http://www.nature.com/nature/journal/v442/n7098/index.html#Books-and-Arts ER - TY - JFULL T1 - Consequential apoptosis in the cerebellum following injury to the developing rat forebrain. A1 - Taylor, DL A1 - Joashi, UC A1 - Sarraf, C A1 - Edwards, AD A1 - Mehmet, H J1 - Brain Pathol Y1 - 2006/07// VL - 16 SN - 1015-6305 SP - 195 EP - 201 N2 - In focal brain lesions, alterations in blood flow and cerebral metabolism can be detected in brain areas remote from the primary injury. The cellular consequences of this phenomenon, originally termed diaschisis, are not fully understood. Here, we report that in two distinct models of forebrain injury, neuronal death in the cerebellum, a site distant to the primary injury, results as consequence of neuronal loss in the forebrain. Fourteen-day-old rats were subjected to unilateral forebrain injury, achieved by either hypoxia-ischemia (right carotid artery ligation and hypoxia) or direct needle injury to brain tissue. At defined times after injury, the presence of apoptosis was investigated by cell morphology, in situ end labeling, electron microscopy and poly-ADP-ribose polymerase (PARP) cleavage. Injury to the rat forebrain following hypoxia-ischemia increased apoptosis in the internal granular and Purkinje cell layers of the cerebellum, a site distant to that of the primary injury. The number of apoptotic cells in the cerebellum was significantly related to cell death in the hippocampus. Similarly, direct needle injury to the forebrain resulted in extensive apoptotic cell death in the cerebellum. These results emphasize the intimate relationship between defined neuronal populations in relatively distant brain areas and suggest a cellular basis for diaschisis. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16911476&query_hl=1 ER - TY - JFULL T1 - Use of gadolinium chloride as a contrast agent for imaging spruce knots by magnetic resonance A1 - Eberhardt, TL A1 - So, CL A1 - Herlihy, AH A1 - So, PW J1 - WOOD FIBER SCI Y1 - 2006/07// VL - 38 SN - 0735-6161 SP - 527 EP - 534 N2 - Treatments of knot-containing spruce wood blocks with a paramagnetic salt, gadolinium (III) chloride, in combination with solvent pretreatments, were evaluated as strategies to enhance the visualization of wood features by magnetic resonance imaging (MRI). Initial experiments with clear wood and excised knot samples showed differences in moisture uptake after pretreatments with selected solvents. For knot-containing spruce wood blocks, increased detail in the images with an ethanol pretreatment was attributed to the removal of extractives thereby resulting in higher moisture contents for the knot wood. Incorporation of the gadolinium-based contrast agent resulted in an abrupt loss in signal for a zone around each knot. Accordingly, the retention of gadolinium ions appears to be selective, thereby allowing the demarcation of what is likely to be compression wood known to surround softwood knots. Applications include studies on wood anatomy by MRI and the modeling of wood defects. The treatment of wood with contrast agents as such also shows promise as a technique to improve our understanding of the localization of different cell-wall chemistries, especially as they relate to ion exchange capacity. ER - TY - JFULL T1 - Myocardial infarction following sickle cell chest syndrome. A1 - Tanner, MA A1 - Westwood, MA A1 - Pennell, DJ J1 - Br J Haematol Y1 - 2006/07// VL - 134 SN - 0007-1048 SP - 2 EP - 2 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16803561&query_hl=1 ER - TY - JFULL T1 - Hepatic vein transit time of SonoVue: a comparative study with Levovist. A1 - Lim, AK A1 - Patel, N A1 - Eckersley, RJ A1 - Goldin, RD A1 - Thomas, HC A1 - Cosgrove, DO A1 - Taylor-Robinson, SD A1 - Blomley, MJ J1 - Radiology Y1 - 2006/07// VL - 240 SN - 0033-8419 SP - 130 EP - 135 N2 - PURPOSE: To prospectively compare transit times of Levovist and SonoVue in healthy volunteers and patients with biopsy-proved hepatitis C-related liver disease. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Forty patients and 25 healthy volunteers were examined. Subjects fasted, a bolus of SonoVue (0.6 mL) was injected into a cubital fossa vein, and hepatic venous time-intensity profiles were measured with spectral Doppler tracing. This was repeated with two injections of Levovist (2 g) and another injection of SonoVue. Time-intensity curves of spectral Doppler signals of right and middle hepatic veins were analyzed. A sustained signal intensity increase of 10% above baseline levels indicated hepatic vein transit time (HVTT). Carotid artery audio intensity was measured in volunteers. Analysis of variance and t tests were used for statistical analysis. RESULTS: Twelve patients had mild hepatitis; 18, moderate or severe hepatitis; and 10, cirrhosis. Mean HVTTs in control, mild hepatitis, moderate or severe hepatitis, and cirrhosis groups were 38.3 seconds +/- 2.4 (standard error), 47.5 seconds +/- 6.5, 29.5 seconds +/- 10.8, and 17.6 seconds +/- 5.0, respectively, with Levovist (P < .001) and 29.4 seconds +/- 6.9, 27.4 seconds +/- 9.3, 22.9 seconds +/- 4.7, and 16.4 seconds +/- 4.9, respectively, with SonoVue (P < .001). HVTT decreased as severity increased at imaging with both contrast agents. There was no significant difference in HVTT between mild and moderate hepatitis groups with SonoVue; however, there were significant differences in HVTT between all patient groups with Levovist. HVTT of SonoVue was shorter than that of Levovist in all groups (P < .001) except the cirrhosis group; in this group, HVTT of the two contrast agents was similar (P = .05). No difference was observed in mean cardiopulmonary transit time for SonoVue or Levovist (9.1 seconds +/- 2.4 [standard error] and 8.4 seconds +/- 2.5, respectively, P = .18). CONCLUSION: HVTT was significantly shorter with SonoVue than with Levovist; there was no significant difference in cardiopulmonary transit time. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16720867&query_hl=1 ER - TY - JFULL T1 - Amyloid load and cerebral atrophy in Alzheimer's disease: An C-11-PIB positron emission tomography study A1 - Archer, HA A1 - Edison, P A1 - Brooks, DJ A1 - Barnes, J A1 - Frost, C A1 - Yeatman, T A1 - Fox, NC A1 - Rossor, MN J1 - ANN NEUROL Y1 - 2006/07// VL - 60 SN - 0364-5134 SP - 145 EP - 147 N2 - To determine the relationship between cerebral amyloid plaque load and rates of cerebral atrophy in Alzheimer's disease. C-11-PIB(C-11-6-OH benzothiazole)PET (positron emission tomography) findings were correlated with volumetric magnetic resonance imaging (MRI) measurements in nine subjects with mild to moderate AD. Analysis revealed a positive correlation between rates of whole brain atrophy and whole brain (p = 0.019) and regional C-11-PIB uptake. This provides support for the central role of amyloid deposition in the pathogenesis of AD. ER - TY - JFULL T1 - Magnetic resonance imaging in perinatal brain injury: clinical presentation, lesions and outcome. A1 - Rutherford, M A1 - Srinivasan, L A1 - Dyet, L A1 - Ward, P A1 - Allsop, J A1 - Counsell, S A1 - Cowan, F J1 - Pediatr Radiol Y1 - 2006/07// VL - 36 SN - 0301-0449 SP - 582 EP - 592 N2 - Neonatal MR imaging is invaluable in assessing the term born neonate who presents with an encephalopathy. Successful imaging requires adaptations to both the hardware and the sequences used for adults. The perinatal and postnatal details often predict the pattern of lesions sustained and are essential for correct interpretation of the imaging findings, but additional or alternative diagnoses in infants with apparent hypoxic ischaemic encephalopathy should always be considered. Perinatally acquired lesions are usually at their most obvious between 1 and 2 weeks of age. Very early imaging (<3 days) may be useful to make management decisions in ventilated neonates, but abnormalities may be subtle at that stage. Diffusion-weighted imaging is clinically useful for the early identification of ischaemic white matter in the neonatal brain but is less reliable in detecting lesions within the basal ganglia and thalami. The pattern of lesions seen on MRI can predict neurodevelopmental outcome. Additional useful information may be obtained by advanced techniques such as MR angiography, venography and perfusion-weighted imaging. Serial imaging with quantification of both structure size and tissue damage provides invaluable insights into perinatal brain injury. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16770663&query_hl=1 ER - TY - JFULL T1 - A controlled trial of skin-to-skin contact in extremely preterm infants. A1 - Miles, R A1 - Cowan, F A1 - Glover, V A1 - Stevenson, J A1 - Modi, N J1 - Early Hum Dev Y1 - 2006/07// VL - 82 SN - 0378-3782 SP - 447 EP - 455 N2 - BACKGROUND: Extremely preterm birth, even in the absence of significant neurological impairment, is associated with altered pain responses and impaired memory and behaviour. Preterm birth increases the risk of maternal depression and may impede the development of the mother-infant relationship, factors that in turn are also associated with impaired infant outcome. Mother-infant skin-to-skin contact has been recommended as a simple means of ameliorating these effects. METHODS: We conducted a pragmatic, prospective, controlled, intention-to-treat trial in two neonatal intensive care units. Infants born below 32 weeks gestation were recruited within the first week after birth and assigned to a control group receiving standard care, or an intervention group in which mothers were encouraged to provide a session of skin-to-skin contact once daily for 4 weeks. We assessed infant behaviour at time of discharge from hospital, responses to immunisation at 4 and 12 months of age, and memory, behaviour and development at 1 year corrected (postmenstrual) age. Indices of maternal depression, stress, anxiety, lactation performance and infant interaction were assessed at time of infant discharge, 4 months and 1 year. RESULTS: No significant difference was identified in any infant or maternal measure at any time point. CONCLUSIONS: Mother-infant skin-to-skin contact after extremely preterm birth results in neither benefit nor adverse consequences. Although there is no reason to dissuade mothers who wish to provide STS contact, we are unable to recommend resource allocation for the implementation of STS programmes for extremely preterm infants in a neonatal intensive care unit setting. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16458458&query_hl=1 ER - TY - JFULL T1 - Comparison between myocardial contrast echocardiography and single-photon emission computed tomography for predicting transmurality of acute myocardial infarction A1 - Hayat, SA A1 - Janardhanan, R A1 - Moon, JCC A1 - Pennell, DJ A1 - Senior, R J1 - AM J CARDIOL Y1 - 2006/06/15/ VL - 97 SN - 0002-9149 SP - 1718 EP - 1721 N2 - Contrast-enhanced cardiovascular magnetic resonance imaging (CMR) has been shown to accurately assess transmural extent of infarction, which is an excellent predictor of long-term improvement in contractile function. We assessed the relative accuracy of myocardial contrast echocardiography (MCE) and single-photon emission computed tomography (SPECT) to predict transmural extent of infarction after acute myocardial infarction. MCE, SPECT, and CMR were performed in 40 patients with acute myocardial infarction 7 to 10 days after thrombolysis. CMR was used to divide the transmural extent of infarction into 5 groups: 0%, 1% to 25%, 26% to 50%, 5 1% to 75%, and 76% to 100% in dysfunctional segments. MCE and SPECT were compared with assessment grades of transmural extent of infarction. There was a significant relation (p < 0.0001) between decreasing contrast intensity as assessed qualitatively by MCE and increasing transmural extent of infarction on CMR as was the case for SPECT. The accuracy of MCE (77%) to predict > 50% transmural extent of infarction (nonviable myocardium) was significantly (p = 0.02) superior to that of SPECT (70%). Absence of uptake,on MCE and SPECT virtually ruled out <= 50% of the transmural extent of infarction (negative predictive values 93% and 89%, respectively). MCE was significantly more sensitive than SPECT in differentiating between <= 25% and > 25% transmural extent of infarction (84% vs 76%, p = 0.03). MCE and SPECT correlate well with the transmural extent of infarction. However, MCE is significantly more accurate in predicting > 50% of the transmural extent. of infarction and more sensitive in identifying <= 25 % of the transmural extent of infarction than SPECT. (c) 2006 Elsevier Inc. All rights reserved. ER - TY - JFULL T1 - Role of microbubble ultrasound contrast agents in the non-invasive assessment of chronic hepatitis C-related liver disease. A1 - Grier, S A1 - Lim, AK A1 - Patel, N A1 - Cobbold, JF A1 - Thomas, HC A1 - Cox, IJ A1 - Taylor-Robinson, SD J1 - World J Gastroenterol Y1 - 2006/06/14/ VL - 12 SN - 1007-9327 SP - 3461 EP - 3465 N2 - Patients who are chronically infected with the hepatitis C virus often develop chronic liver disease and assessment of the severity of liver injury is required prior to considering viral eradication therapy. This article examines the various assessment methods currently available from gold standard liver biopsy to serological markers and imaging. Ultrasound is one of the most widely used imaging modalities in clinical practice and is already a first-line diagnostic tool for liver disease. Microbubble ultrasound contrast agents allow higher resolution images to be obtained and functional assessments of microvascular change to be carried out. The role of these agents in quantifying the state of hepatic injury is discussed as a viable method of determining the stage and grade of liver disease in patients with hepatitis C. Although currently confined to specialist centres, the availability of microbubble contrast-enhanced ultrasound will inevitably increase in the clinical setting. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16773702&query_hl=1 ER - TY - JFULL T1 - Microglial activation correlates with severity in Huntington disease: a clinical and PET study. A1 - Pavese, N A1 - Gerhard, A A1 - Tai, YF A1 - Ho, AK A1 - Turkheimer, F A1 - Barker, RA A1 - Brooks, DJ A1 - Piccini, P J1 - Neurology Y1 - 2006/06/13/ VL - 66 SN - 1526-632X SP - 1638 EP - 1643 N2 - BACKGROUND: Huntington disease (HD) is characterized by the progressive death of medium spiny dopamine receptor bearing striatal GABAergic neurons. In addition, microglial activation in the areas of neuronal loss has recently been described in postmortem studies. Activated microglia are known to release neurotoxic cytokines, and these may contribute to the pathologic process. METHODS: To evaluate in vivo the involvement of microglia activation in HD, the authors studied patients at different stages of the disease using [(11)C](R)-PK11195 PET, a marker of microglia activation, and [(11)C]raclopride PET, a marker of dopamine D2 receptor binding and hence striatal GABAergic cell function. RESULTS: In HD patients, a significant increase in striatal [(11)C](R)-PK11195 binding was observed, which significantly correlated with disease severity as reflected by the striatal reduction in [(11)C]raclopride binding, the Unified Huntington's Disease Rating Scale score, and the patients' CAG index. Also detected were significant increases in microglia activation in cortical regions including prefrontal cortex and anterior cingulate. CONCLUSIONS: These [(11)C](R)-PK11195 PET findings show that the level of microglial activation correlates with Huntington disease (HD) severity. They lend support to the view that microglia contribute to the ongoing neuronal degeneration in HD and indicate that [(11)C](R)-PK11195 PET provides a valuable marker when monitoring the efficacy of putative neuroprotecting agents in this relentlessly progressive genetic disorder. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16769933&query_hl=1 ER - TY - JFULL T1 - Sub-wavelength imaging at radio frequency A1 - Wiltshire, MCK A1 - Pendry, JB A1 - Hajnal, JV J1 - J PHYS-CONDENS MAT Y1 - 2006/06/07/ VL - 18 SN - 0953-8984 SP - L315 EP - L321 N2 - A slab of material with a negative permeability can act as a super-lens for magnetic fields and generate images with a sub-wavelength resolution. We have constructed an effective medium using a metamaterial with negative permeability in the region of 24MHz, and used this to form images in free space of radio frequency magnetic sources. Measurements of these images show that a resolution of approximately lambda/64 has been achieved, consistent with both analytical and numerical predictions. ER - TY - JFULL T1 - Expression of indoleamine 2,3-dioxygenase (IDO) by endothelial cells: implications for the control of alloresponses. A1 - Beutelspacher, SC A1 - Tan, PH A1 - McClure, MO A1 - Larkin, DF A1 - Lechler, RI A1 - George, AJ J1 - Am J Transplant Y1 - 2006/06// VL - 6 SN - 1600-6135 SP - 1320 EP - 1330 N2 - Indoleamine 2,3-dioxygenase (IDO) is an important enzyme in the regulation of immune responses; cells that express IDO can suppress T-cell responses and promote tolerance. Because of the critical role of endothelial cells in graft rejection, we have investigated the role of IDO expression by vascular endothelial cells and its consequence on immunoregulation. We compared the expression of IDO by primary human umbilical vein endothelial cells (HUVECs), human saphenous vein endothelial cells (HSVECs) and arterially derived endothelial cells using reverse transcriptase PCR, Western blotting and assays for enzymatic activity. In HUVECs IDO is upregulated by incubation with cytokines or in mycoplasma-infected cells. On the other hand HSVECs and arterially derived endothelial cells express little IDO, which is poorly upregulated upon activation (except by mycoplasma). Inhibition of IDO activity improved the ability of HUVECs to stimulate allogeneic T-cell responses. If either HUVECs or HSVECs are transfected with the gene encoding IDO, then they are incapable of stimulating allogeneic T-cell responses and induce anergy in allospecific T cells (which can also act as regulatory cells). The variable expression of IDO in different endothelial cells is important not only in understanding the role of endothelial cells in the regulation of graft rejection, but also as a potential therapeutic strategy. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16686756&query_hl=1 ER - TY - JFULL T1 - Magnetic resonance and ultrasound techniques for the evaluation of hepatic fibrosis. A1 - Cobbold, J A1 - Lim A A1 - Wylezinska M A1 - Cunningham C A1 - Crossey M A1 - Thomas H A1 - Patel N A1 - Cox J A1 - Taylor-Robinson J1 - Hepatology Y1 - 2006/06// IS - 6 VL - 43 SP - 1401 EP - 1402 UR - http://www3.interscience.wiley.com/cgi-bin/fulltext/112636849/PDFSTART ER - TY - JFULL T1 - Cadaver validation of intensity-based ultrasound to CT registration A1 - Penney GP A1 - Barratt DC A1 - Chan CSK A1 - Slomczykowski M A1 - Carter TJ A1 - Edwards PJ A1 - Hawkes DJ J1 - Medical Image Analysis Y1 - 2006/06// IS - 3 VL - 10 SN - 1361-8415 SP - 385 EP - 395 ER - TY - JFULL T1 - Upregulation of dopamine D2 receptors in dopaminergic drug-naive patients with Parkin gene mutations. A1 - Scherfler, C A1 - Khan, NL A1 - Pavese, N A1 - Lees, AJ A1 - Quinn, NP A1 - Brooks, DJ A1 - Piccini, PP J1 - Mov Disord Y1 - 2006/06// VL - 21 SN - 0885-3185 SP - 783 EP - 788 N2 - Medicated patients with Parkinsonism and parkin gene mutations have been reported to show a significant decrease in striatal dopamine D2 receptors (D2R) in comparison to medicated idiopathic Parkinson's disease (IPD) patients with similar age and disease severity. The aim of this study was to verify whether the genetic defect per se is responsible for this decrease. We have studied with [11C]raclopride (RAC) positron emission tomography (PET) in a group of 14 sporadic patients with parkin-linked Parkinsonism, 6 of whom had never received levodopa or dopamine agonists. The remaining 8 patients had been treated with levodopa for at least 5 years. Presynaptic striatal [18F]dopa storage was not significantly different between these two groups of patients. In untreated parkin-positive patients, significant putaminal increases in RAC-binding potential (BP) were found in comparison to an age-matched healthy control group by using a classical region of interest approach and statistical parametric mapping. In contrast, levodopa-treated parkin-positive patients showed significant decreases in RAC-BP in the caudate and putamen when compared to an age-matched healthy control group. The RAC PET findings revealed that striatal D2R upregulation occurs in dopaminergic drug-naive parkin-positive patients, in a similar fashion to the upregulation reported in drug-naive IPD. D2R downregulation observed in medicated parkin-positive patients, therefore, is not caused primarily by the genetic defect itself. Parkin-positive patients appear to have a greater susceptibility to the exposure to dopaminergic medication than IPD patients, which in turn might be an indirect effect of their genetic mutation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16511856&query_hl=1 ER - TY - JFULL T1 - Does oxygen concentration used for resuscitation influence outcome of asphyxiated newly born infants treated with hypothermia? Reply A1 - Thoresen, M A1 - Whitelaw, A A1 - Azzopardi, D A1 - Renowden, S A1 - Edwards, AD A1 - Rutherford, MA J1 - PEDIATRICS Y1 - 2006/06// VL - 117 SN - 0031-4005 SP - 2328 EP - 2328 ER - TY - JFULL T1 - Strategies to improve non-viral vectors--potential applications in clinical transplantation. A1 - Tan, PH A1 - Chan, CL A1 - George, AJ J1 - Expert Opin Biol Ther Y1 - 2006/06// VL - 6 SN - 1744-7682 SP - 619 EP - 630 N2 - Prevention of acute rejection has been well controlled with immunosuppressive drugs. However, the long-term control of rejection is less satisfactory and the side effects of chronic usage of these drugs are far from acceptable. Thus, more imaginative options for therapy need to be explored. Gene therapy has potential promise in preserving allografts, preventing rejection and inducing tolerance. Despite this initial promise in many animal models, the translation of gene therapy to the clinical arena has been slow. This may be related in part to the deficiencies in vector development. Existing viral vectors are efficient at transducing allografts, but they induce inflammatory and pathogenic effects. Although the alternative non-viral systems are relatively innocuous, they are less efficient at gene delivery. This review systematically analyses the limitations of non-viral vector technology and the strategies that have been developed to overcome these limitations. Future development of non-viral vectors may have potential application in clinical transplantation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16706608&query_hl=1 ER - TY - JFULL T1 - Sequential neurological examinations in infants with neonatal encephalopathy and low apgar scores: relationship with brain MRI. A1 - Ricci, D A1 - Guzzetta, A A1 - Cowan, F A1 - Haataja, L A1 - Rutherford, M A1 - Dubowitz, L A1 - Mercuri, E J1 - Neuropediatrics Y1 - 2006/06// VL - 37 SN - 0174-304X SP - 148 EP - 153 N2 - OBJECTIVE: The aims of this study were to (a) describe the evolution of neurological signs after the neonatal period in infants with neonatal encephalopathy and abnormal outcome and (b) to establish the relationship between the evolution of neurological signs and patterns of lesions on brain MRI. PATIENTS: Fifteen children with low Apgar scores, abnormal neurological signs at the end of the neonatal period, and abnormal outcome were examined at 1 - 2 weeks, 5 - 7 weeks, and 6 months. All the infants had at least one MRI scan performed in the neonatal period. RESULTS: All infants had persistent abnormalities on all examinations performed but the severity of neurological impairment was variable and was related to the pattern of brain lesions. Infants with severe basal ganglia and white matter lesions showed abnormal axial and limb tone, movements, and visual function on all the examinations and none achieved independent sitting. In infants with moderate basal ganglia lesions and/or severe white matter changes, visual function and feeding improved by 5 - 7 weeks and were still normal at 6 months while limb tone, which was reduced in the first weeks, appeared to be normal at 5 - 6 weeks but was found to be increased at 6 months; all were able to sit unsupported at 2 years and most of them achieved the ability to walk with support. CONCLUSIONS: Our results suggest that the evolution of the neurological patterns after the neonatal period in infants with persisting neonatal abnormalities depends on their pattern of brain lesions. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16967366&query_hl=1 ER - TY - JFULL T1 - Keeping abreast of advances in fetal cardiology. A1 - Gardiner, HM J1 - Early Hum Dev Y1 - 2006/06// VL - 82 SN - 0378-3782 SP - 415 EP - 419 N2 - Advances in genetics and computing have contributed to a better understanding of the mechanisms underlying cardiovascular development, its programming and possible therapeutic manipulation. Pre-conceptual folate can reduce the prevalence of cardiac malformations and improvements in imaging allow us to detect congenital heart disease and assess function at earlier gestations. Three- and four-dimensional imaging may improve the surgeons' understanding of complex vascular malformations as well as permitting remote diagnosis. Treatment of fetal arrhythmias may be rationalised by fetal electrocardiography and magnetocardiography and by further defining the natural history of complete heart block and mechanisms of tachyarrhythmia. Tissue engineering and robotics may improve the surgical outcome for children by creating conduits with growth potential thus reducing the need for multiple surgical procedures. These technologies may permit successful fetal surgical procedures. Cross discipline collaboration has been key in enabling these advances which have changed the face of fetal cardiology. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16387457&query_hl=1 ER - TY - JFULL T1 - Comparison of the dual receptor endothelin antagonist enrasentan with enalapril in asymptomatic left ventricular systolic dysfunction: a cardiovascular magnetic resonance study. A1 - Prasad, SK A1 - Dargie, HJ A1 - Smith, GC A1 - Barlow, MM A1 - Grothues, F A1 - Groenning, BA A1 - Cleland, JG A1 - Pennell, DJ J1 - Heart Y1 - 2006/06// VL - 92 SN - 1468-201X SP - 798 EP - 803 N2 - OBJECTIVE: To compare the effect of the dual endothelin A/B receptor antagonist enrasentan with enalapril on left ventricular (LV) remodelling. METHODS: Multicentre, randomised, double blind, parallel group study of 72 asymptomatic patients with LV dysfunction. Patients received enrasentan (60-90 mg/day) or enalapril (10-20 mg/day). The primary end point was the change in LV end diastolic volume index (EDVI) after six months' treatment. RESULTS: LV EDVI increased with enrasentan but decreased with enalapril (3.9 (1.8) v -3.4 (1.4) ml/m2, p = 0.001). Enrasentan increased resting cardiac index compared with enalapril (0.11 (0.07) v -0.10 (0.07) l/m2, p = 0.04), as well as LV mass index (0.67 (1.6) v -3.6 (1.6) g/m2, p = 0.04). Other variables were comparable between groups. Enalapril lowered brain natriuretic peptide more than enrasentan (-19.3 (9.4) v -5.8 (6.9) pg/ml, p = 0.005). Noradrenaline (norepinephrine) (p = 0.02) increased more with enrasentan than with enalapril. Enrasentan was associated with more serious adverse events compared with enalapril (six (16.7%) patients v one (2.8%), p = 0.02); the rate of progression of heart failure did not differ. CONCLUSION: In asymptomatic patients with LV dysfunction, LV EDVI increased over six months with enrasentan compared with enalapril treatment, with adverse neurohormonal effects. This suggests that enrasentan at a dose of 60-90 mg/day over six months causes adverse ventricular remodelling despite an increase in the resting cardiac index. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16339819&query_hl=1 ER - TY - JFULL T1 - Current and future applications of magnetic resonance imaging and spectroscopy of the brain in hepatic encephalopathy. A1 - Grover, VP A1 - Dresner, MA A1 - Forton, DM A1 - Counsell, S A1 - Larkman, DJ A1 - Patel, N A1 - Thomas, HC A1 - Taylor-Robinson, SD J1 - World J Gastroenterol Y1 - 2006/05/21/ VL - 12 SN - 1007-9327 SP - 2969 EP - 2978 N2 - Hepatic encephalopathy (HE) is a common neuro-psychiatric abnormality, which complicates the course of patients with liver disease and results from hepatocellular failure and/or portosystemic shunting. The manifestations of HE are widely variable and involve a spectrum from mild subclinical disturbance to deep coma. Research interest has focused on the role of circulating gut-derived toxins, particularly ammonia, the development of brain swelling and changes in cerebral neurotransmitter systems that lead to global CNS depression and disordered function. Until recently the direct investigation of cerebral function has been difficult in man. However, new magnetic resonance imaging (MRI) techniques provide a non-invasive means of assessment of changes in brain volume (coregistered MRI) and impaired brain function (fMRI), while proton magnetic resonance spectroscopy (1H MRS) detects changes in brain biochemistry, including direct measurement of cerebral osmolytes, such as myoinositol, glutamate and glutamine which govern processes intrinsic to cellular homeostasis, including the accumulation of intracellular water. The concentrations of these intracellular osmolytes alter with hyperammonaemia. MRS-detected metabolite abnormalities correlate with the severity of neuropsychiatric impairment and since MR spectra return towards normal after treatment, the technique may be of use in objective patient monitoring and in assessing the effectiveness of various treatment regimens. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16718775&query_hl=1 ER - TY - JFULL T1 - Cholangiocarcinoma (vol 366, pg 1303, 2005) A1 - Khan, SA A1 - Thomas, HC A1 - Davidson, BR A1 - Taylor-Robinson, SD J1 - LANCET Y1 - 2006/05/20/ VL - 367 SN - 0140-6736 SP - 1656 EP - 1656 ER - TY - JFULL T1 - Magnetic resonance imaging in perinatal brain injury: clinical presentation, lesions and outcome. A1 - Rutherford, M A1 - Srinivasan, L A1 - Dyet, L A1 - Ward, P A1 - Allsop, J A1 - Counsell, S A1 - Cowan, F J1 - Pediatr Radiol Y1 - 2006/05/16/ SN - 0301-0449 N2 - Neonatal MR imaging is invaluable in assessing the term born neonate who presents with an encephalopathy. Successful imaging requires adaptations to both the hardware and the sequences used for adults. The perinatal and postnatal details often predict the pattern of lesions sustained and are essential for correct interpretation of the imaging findings, but additional or alternative diagnoses in infants with apparent hypoxic ischaemic encephalopathy should always be considered. Perinatally acquired lesions are usually at their most obvious between 1 and 2 weeks of age. Very early imaging (<3 days) may be useful to make management decisions in ventilated neonates, but abnormalities may be subtle at that stage. Diffusion-weighted imaging is clinically useful for the early identification of ischaemic white matter in the neonatal brain but is less reliable in detecting lesions within the basal ganglia and thalami. The pattern of lesions seen on MRI can predict neurodevelopmental outcome. Additional useful information may be obtained by advanced techniques such as MR angiography, venography and perfusion-weighted imaging. Serial imaging with quantification of both structure size and tissue damage provides invaluable insights into perinatal brain injury. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16703343&query_hl=1 ER - TY - JFULL T1 - Imaging in Parkinson's disease: the role of monoamines in behavior. A1 - Brooks, DJ A1 - Piccini, P J1 - Biol Psychiatry Y1 - 2006/05/15/ VL - 59 SN - 0006-3223 SP - 908 EP - 918 N2 - Positron emission tomography (PET) and single photon emission computed tomography (SPECT) can measure striatal dopamine (DA) terminal function in vivo as reflected by DA storage capacity and transporter binding. In Parkinson's disease (PD) posterior dorsal putamen DA terminals are initially targeted, the anterior putamen and head of caudate subsequently becoming affected. In contrast, dopaminergic function in pallidal, amygdala, and cingulate regions is upregulated in early PD and only later becomes reduced. Rigidity and bradykinesia in PD have been shown to correlate with loss of putamen dopaminergic function, whereas performance on executive and working memory tasks correlates with integrity of caudate dopaminergic terminals. 11C-RTI32 PET, a marker of noradrenergic and dopaminergic transporter binding, can be used to assess noradrenergic along with dopaminergic terminal function. Serotonergic transporter binding can be assessed with 11C-DASB PET and 123I-beta CIT SPECT, whereas HT1A binding can be measured with 11C-WAY100635 PET. With these modalities, the relationship between mood, noradrenergic and serotonergic function can be examined in PD. The functional effects of focal DA replacement on DA storage capacity and patterns of brain activation via implantation of fetal midbrain cells or glial derived neurotrophic factor (GDNF) infusion into putamen of PD patients has been examined with PET. Both approaches lead to consistently increased levels of putamen 18F-dopa uptake, and cell implantation can restore levels of frontal activation. Clinical outcome, however, has proved to be variable and off-medication dyskinesias are an unwanted side effect in transplanted cases. Dopamine release after pharmacological challenges or during behavioral tasks can be assessed indirectly by studying changes in receptor availability to PET radioligands. Stereotyped sequential movements are associated with striatal DA release, and this increases with more complex behaviors and the presence of financial incentives, which also increase frontal DA levels. Parkinson patients release less putamen DA than healthy control subjects during stereotyped finger movements. Interestingly, those PD patients who develop a dopa dependency syndrome, craving their medication, generate significantly greater levels of ventral striatal DA compared with similarly disabled patients without such a psychological dependency. In the future, functional imaging is likely to throw light on the roles of peptide transmission in regulating mood and behavior as non-peptide analogue ligands become available. Novel markers of amyloid plaque load will also help clarify the etiology of dementia in PD. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16581032&query_hl=1 ER - TY - JFULL T1 - Effect of strain on actomyosin kinetics in isometric muscle fibers. A1 - Siththanandan, VB A1 - Donnelly, JL A1 - Ferenczi, MA J1 - Biophys J Y1 - 2006/05/15/ VL - 90 SN - 0006-3495 SP - 3653 EP - 3665 N2 - Investigations were conducted into the biochemical and mechanical states of cross-bridges during isometric muscle contraction. Rapid length steps (3 or 6 nm hs(-1)) were applied to rabbit psoas fibers, permeabilized and isometric, at either 12 degrees C or 20 degrees C. Fibers were activated by photolysis of P(3)-1-(2-nitrophenyl)-ethyl ester of ATP infused into rigor fibers at saturating Ca(2+). Sarcomere length, tension, and phosphate release were recorded-the latter using the MDCC-PBP fluorescent probe. A reduction in strain, induced by a rapid release step, produced a short-lived acceleration of phosphate release. Rates of the phosphate transient and that of phases 3 and 4 of tension recovery were unaffected by step size but were elevated at higher temperatures. In contrast the amplitude of the phosphate transient was smaller at 20 degrees C than 12 degrees C. The presence of 0.5 or 1.0 mM added ADP during a release step reduced both the rate of tension recovery and the poststep isometric tension. A kinetic scheme is presented to simulate the observed data and to precisely determine the rate constants for the elementary steps of the ATPase cycle. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16513783&query_hl=1 ER - TY - JFULL T1 - Randomized controlled trial of deferiprone or deferoxamine in beta-thalassemia major patients with asymptomatic myocardial siderosis. A1 - Pennell, DJ A1 - Berdoukas, V A1 - Karagiorga, M A1 - Ladis, V A1 - Piga, A A1 - Aessopos, A A1 - Gotsis, ED A1 - Tanner, MA A1 - Smith, GC A1 - Westwood, MA A1 - Wonke, B A1 - Galanello, R J1 - Blood Y1 - 2006/05/01/ VL - 107 SN - 0006-4971 SP - 3738 EP - 3744 N2 - Most deaths in beta-thalassemia major result from cardiac complications due to iron overload. Differential effects on myocardial siderosis may exist between different chelators. A randomized controlled trial was performed in 61 patients previously maintained on subcutaneous deferoxamine. The primary end point was the change in myocardial siderosis (myocardial T2(*)) over 1 year in patients maintained on subcutaneous deferoxamine or those switched to oral deferiprone monotherapy. The dose of deferiprone was 92 mg/kg/d and deferoxamine was 43 mg/kg for 5.7 d/wk. Compliance was 94% +/- 5.3% and 93% +/- 9.7% (P = .81), respectively. The improvement in myocardial T2(*) was significantly greater for deferiprone than deferoxamine (27% vs 13%; P = .023). Left ventricular ejection fraction increased significantly more in the deferiprone-treated group (3.1% vs 0.3% absolute units; P = .003). The changes in liver iron level (-0.93 mg/g dry weight vs -1.54 mg/g dry weight; P = .40) and serum ferritin level (-181 microg/L vs -466 microg/L; P = .16), respectively, were not significantly different between groups. The most frequent adverse events were transient gastrointestinal symptoms for deferiprone-treated patients and local reactions at the infusion site for deferoxamine. There were no episodes of agranulocytosis. Deferiprone monotherapy was significantly more effective than deferoxamine over 1 year in improving asymptomatic myocardial siderosis in beta-thalassemia major. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16352815&query_hl=1 ER - TY - JFULL T1 - Parallel imaging. A1 - Hajnal, JV A1 - Larkman, DJ J1 - NMR Biomed Y1 - 2006/05// VL - 19 SN - 0952-3480 SP - 287 EP - 287 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16705629&query_hl=1 ER - TY - JFULL T1 - Movement disorders A1 - Brooks, DJ J1 - J NEUROL Y1 - 2006/05// VL - 253 SN - 0340-5354 SP - 4 EP - 4 ER - TY - JFULL T1 - Accuracy of low power contrast echocardiography for the assessment of left ventricular remodelling compared with single-photon emission computed tomography following acute myocardial: Comparison with cardiovascular magnetic resonance imaging A1 - Lim, T A1 - Burden, L A1 - Janardhanan, R A1 - Dwivedi, G A1 - Chai, P A1 - Moon, J A1 - Pennell, D A1 - Senior, R J1 - HEART Y1 - 2006/05// VL - 92 SN - 1355-6037 SP - A43 EP - A43 ER - TY - JFULL T1 - Analysis of p53 mutations for a mutational signature in human intrahepatic cholangiocarcinoma. A1 - Khan, SA A1 - Taylor-Robinson, SD A1 - Carmichael, PL A1 - Habib, N A1 - Lemoine, NR A1 - Thomas, HC J1 - Int J Oncol Y1 - 2006/05// VL - 28 SN - 1019-6439 SP - 1269 EP - 1277 N2 - Cholangiocarcinoma development may be related to cholangiocyte DNA damage from genotoxic compounds in bile. We have previously shown that human biliary tissue is exposed to genotoxic agents, as evidenced by the presence of DNA adducts. Establishing the presence of a 'mutational signature' in tumour suppressor genes from tumour tissue provides a means of linking cause and effect in human cancer. Inactivation of p53, known to have 'hot-spots' for particular chemical carcinogens, has previously been linked to human cholangiocarcinoma. However, previous p53 studies have focused on exons 5-8, potentially missing gene alterations at other sites. This study examined the putative link between environmental carcinogens and intrahepatic cholangiocarcinoma by analysing DNA from 31 patients for complete p53 mutational signatures, using single strand conformational polymorphism and polymerase chain reaction. All mutations found were compared to known p53 mutations in cholangiocarcinoma and to mutations induced by environmental mutagens, as described in p53 databases. Five non-silent p53 mutations were found, including three new frameshift mutations and two new intron mutations which have not previously been reported in cholangiocarcinoma. Two frameshifts were due to deletions and the third due to an insertion in exon 5. There was no predominant mutational spectrum amongst the set of cholangiocarcinoma samples studied, or on combining these mutations with the dataset of known p53 mutations in cholangiocarcinoma. Several reasons may explain this, including lack of data outside exons 5-8, bias in mutation reporting, the involvement of mutations in non-coding regions or genes other than p53, or the possibility that there is no carcinogenic specific agent and therefore no signature. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16596244&query_hl=1 ER - TY - JFULL T1 - Limitations of standard transthoracic echocardiography to assess cardiovascular consequences of transfusional iron overload in thalassaemia major A1 - Nair, S A1 - Tanner, M A1 - Galanello, R A1 - Pennell, D A1 - Walker, J J1 - HEART Y1 - 2006/05// VL - 92 SN - 1355-6037 SP - A29 EP - A29 ER - TY - JFULL T1 - Compulsive drug use linked to sensitized ventral striatal dopamine transmission A1 - Evans, AH A1 - Pavese, N A1 - Lawrence, AD A1 - Tai, YF A1 - Appel, S A1 - Doder, M A1 - Brooks, DJ A1 - Lees, AJ A1 - Piccini, P J1 - ANN NEUROL Y1 - 2006/05// VL - 59 SN - 0364-5134 SP - 852 EP - 858 N2 - Objective: A small group of Parkinson's disease (PD) patients compulsively use dopaminergic drugs despite causing harmful social, psychological, and physical effects and fulfil core Diagnostic and Statistical Manual (of Mental Disorders) Fourth Edition criteria for substance dependence (dopamine dysregulation syndrome [DDS]). We aimed to evaluate levodopa-induced dopamine neurotransmission in the striatum of patients with DDS compared with PD control patients.Methods: We used a two-scan positron emission tomography protocol to calculate the percentage change in C-11-raclopride binding potential from a baseline withdrawal (off drug) state to the binding potential after an oral dose of levodopa. We related the subjective effects of levodopa to the effects on endogenous dopamine release of a pharmacological challenge with levodopa in eight control PD patients and eight patients with DDS.Results: PD patients with DDS exhibited enhanced levodopa-induced ventral striatal dopamine release compared with levodopatreated patients with PD not Compulsively taking dopaminergic drugs. The sensitized ventral striatal dopamine neurotransmission produced by levodopa in these individuals correlated with self-reported compulsive drug "wanting" but not "liking" and was related to heightened psychomotor activation (punding).Interpretation: This provides evidence that links sensitization of ventral striatal circuitry in humans to compulsive drug use. ER - TY - JFULL T1 - White matter damage in neonatal enterovirus meningoencephalitis. A1 - Verboon-Maciolek, MA A1 - Groenendaal, F A1 - Cowan, F A1 - Govaert, P A1 - van Loon, AM A1 - de Vries, LS J1 - Neurology Y1 - 2006/04/25/ VL - 66 SN - 1526-632X SP - 1267 EP - 1269 N2 - The authors report six neonates with enteroviral meningoencephalitis. Five infants presented with prolonged seizures, and one presented with systemic enteroviral disease. Cranial ultrasonography showed increased echogenicity in the periventricular white matter, and MRI confirmed mild to severe white matter damage in all infants, which looked similar to periventricular leukomalacia. Two infants developed cerebral palsy: one was neurologically suspect at age 18 months, and three were developmentally normal. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16636251&query_hl=1 ER - TY - JFULL T1 - Myocardial salvage - Retrospection, resolution, and radio waves A1 - Pennell, D J1 - CIRCULATION Y1 - 2006/04/18/ VL - 113 SN - 0009-7322 SP - 1821 EP - 1823 ER - TY - JFULL T1 - Relationship between the distribution of microglial activation, amyloid plaque load and cerebral glucose metabolism in Alzheimer's disease (AD): An 11C-PK11195, 18F-FDG and 11C-PIB PET study. A1 - Edison, P A1 - Archer, H A1 - Hinz, R A1 - Fox, N A1 - Brooks, DJ J1 - J AM GERIATR SOC Y1 - 2006/04// VL - 54 SN - 0002-8614 SP - S6 EP - S7 ER - TY - JFULL T1 - Reduced fractional anisotropy on diffusion tensor magnetic resonance imaging after hypoxic-ischemic encephalopathy. A1 - Ward, P A1 - Counsell, S A1 - Allsop, J A1 - Cowan, F A1 - Shen, Y A1 - Edwards, D A1 - Rutherford, M J1 - Pediatrics Y1 - 2006/04// VL - 117 SN - 1098-4275 SP - e619 EP - e630 N2 - OBJECTIVE: Apparent diffusion coefficients (ADC) that are measured by diffusion-weighted imaging are reduced in severe white matter (WM) and in some severe basal ganglia and thalamic (BGT) injury in infants who present with hypoxic-ischemic encephalopathy (HIE). However, ADC values may pseudonormalize or even be high during this time in some less severe but clinically significant injuries. We hypothesized that fractional anisotropy (FA), a measure of the directional diffusivity of water made using diffusion tensor imaging, may be abnormal in these less severe injuries; therefore, the objective of this study was to use diffusion tensor imaging to measure ADC and FA in infants with moderate and severe hypoxic-ischemic brain injury. METHODS: Twenty infants with HIE and 7 normal control infants were studied. All infants were born at >36 weeks' gestational age, and MRI scans were obtained within 3 weeks of delivery. Data were examined for normality, and comparisons were made using analysis of variance or Kruskal-Wallis as appropriate. RESULTS: During the first week, FA values were decreased with both severe and moderate WM and BGT injury as assessed by conventional imaging, whereas ADC values were reduced only in severe WM injury and some severe BGT injury. Abnormal ADC values pseudonormalized during the second week, whereas FA values continued to decrease. CONCLUSION: FA is reduced in moderate brain injury after HIE. A low FA may reflect a breakdown in WM organization. Moderate BGT injury may result in atrophy but not overt infarction; it is possible that delayed apoptosis is more marked than immediate necrosis, and this may account for normal early ADC values. The accompanying low FA within some severe and all moderate gray matter lesions, which is associated with significant later impairment, may help to confirm clinically significant abnormality in infants with normal ADC values. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16510613&query_hl=1 ER - TY - JFULL T1 - MRI T2* measurements show no myocardial iron loading in multi-transfused low-risk MDS patients A1 - Chacko, J A1 - Pennell, D A1 - Tanner, M A1 - Wonke, B A1 - Hamblin, T A1 - Killick, S J1 - BRIT J HAEMATOL Y1 - 2006/04// VL - 133 SN - 0007-1048 SP - 17 EP - 17 ER - TY - JFULL T1 - Prediction of specific absorption rate in mother and fetus associated with MRI examinations during pregnancy. A1 - Hand, JW A1 - Li, Y A1 - Thomas, EL A1 - Rutherford, MA A1 - Hajnal, JV J1 - Magn Reson Med Y1 - 2006/04// VL - 55 SN - 0740-3194 SP - 883 EP - 893 N2 - There is uncertainty regarding the risk posed by magnetic resonance imaging (MRI) examinations to pregnant patients. The most frequently used methods, such as single-shot fast spin echo (ssFSE), often require operation at the specific absorption rate (SAR) limits imposed by safety guidelines. With the introduction of higher-field systems, such limits will be even more significant for fetal imaging. An electromagnetic solver based on the time domain finite integration technique (FIT) was used to predict SAR in an anatomically realistic model of a pregnant patient (28 weeks' gestation) associated with the radiofrequency (RF) fields from birdcage body coils typical of 1.5 T and 3 T MRI systems (i.e., operating at approximately 64 and 127 MHz, respectively). The results suggest that 1) the highest local SAR is in the mother, with the fetus being exposed to a peak of approximately 40-60% of that value at 64 MHz, increasing to approximately 50-70% at 127 MHz; 2) compliance with U.S. Food and Drug Administration (FDA) and International Commission on Non-Ionizing Radiation Protection (ICNIRP) guidelines requires control of SAR values averaged over 1 g or 10 g of tissue, respectively; and 3) compliance with Medical Device Agency (MDA) guidelines requires control of the maximum SAR(10g) within the fetus. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16508913&query_hl=1 ER - TY - JFULL T1 - Using CFSE data to model the dynamics of immune suppression by CD25+ T cells A1 - Chan, C A1 - Yates, A A1 - Rovis, F A1 - George, A A1 - Garden, O A1 - Stark, J J1 - J IMMUNOL Y1 - 2006/04/01/ VL - 176 SN - 0022-1767 SP - S216 EP - S216 ER - TY - JFULL T1 - Variations due to analysis technique in intracellular pH measurements in simulated and in vivo 31P MR spectra of the human brain. A1 - Hamilton, G A1 - Allsop, JM A1 - Patel, N A1 - Forton, DM A1 - Thomas, HC A1 - O'Sullivan, CP A1 - Hajnal, JV A1 - Taylor-Robinson, SD J1 - J Magn Reson Imaging Y1 - 2006/04// VL - 23 SN - 1053-1807 SP - 459 EP - 464 N2 - PURPOSE: To investigate variation in pH generated by different analysis techniques and to find the most robust method, 31P MR brain spectra were acquired in vivo. Three different methods were used to measure the chemical shift of inorganic phosphate (Pi) relative to phosphocreatine (PCr). MATERIALS AND METHODS: Eight healthy volunteers were scanned four times, and manual measurement of the chemical shift in a frequency domain spectrum using the manufacturer's software was compared with values produced by a frequency-domain analysis method (NMR1) and a prior-knowledge-based time-domain technique (MRUI). To explain the in vivo data, simulations of brain spectra, modified in ways typical of real variations in vivo, were produced and the pH was measured using manual measurement and MRUI. RESULTS: Different measurement techniques produced systematically different pH values, with manual measurement producing the lowest variability (manual measurement: pH = 6.999, CoV = 0.297; NMR1: pH = 7.042, CoV = 0.501; MRUI: pH = 7.036, CoV = 0.606). While MRUI more accurately measured the pH of unaltered simulations, it was systematically affected by altering the simulated spectra. Manual measurement was unaffected. CONCLUSION: Manual measurement produces the most consistent pH value, and there is no benefit in using more complex automated spectral fitting methods to measure the pH. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16506142&query_hl=1 ER - TY - JFULL T1 - In vivo imaging of cerebral "peripheral benzodiazepine binding sites" in patients with hepatic encephalopathy. A1 - Cagnin, A A1 - Taylor-Robinson, SD A1 - Forton, DM A1 - Banati, RB J1 - Gut Y1 - 2006/04// VL - 55 SN - 0017-5749 SP - 547 EP - 553 N2 - BACKGROUND AND AIMS: One proposed mechanism whereby hepatic encephalopathy (HE) leads to loss of brain function is dysregulated synthesis of neurosteroids. Mitochondrial synthesis of neurosteroids is regulated by "peripheral benzodiazepine binding sites" (PBBS). Expressed in the brain by activated glial cells, PBBS can be measured in vivo by the specific ligand [11C](R)-PK11195 and positron emission tomography (PET). Recently, it has been suggested that PBBS expressing glial cells may play a role in the general inflammatory responses seen in HE. Therefore, we measured PBBS in vivo in the brains of patients with minimal HE using [11C](R)-PK11195 PET. METHODS: Five patients with minimal HE and biopsy proven cirrhosis of differing aetiology were assessed with a neuropsychometric battery. Regional expression of PBBS in the brain was detected by [11C](R)-PK11195 PET. RESULTS: All patients showed brain regions with increased [11C](R)-PK11195 binding. Significant increases in glial [11C](R)-PK11195 binding were found bilaterally in the pallidum, right putamen, and right dorsolateral prefrontal region. The patient with the most severe cognitive impairment had the highest increases in regional [11C](R)-PK11195 binding. CONCLUSION: HE is associated with increased cerebral binding of [11C](R)-PK11195 in vivo, reflecting increased expression of PBBS by glial cells. This supports earlier experimental evidence in rodent models of liver failure, suggesting that an altered glial cell state, as evidenced by the increase in cerebral PBBS, might be causally related to impaired brain functioning in HE. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16210399&query_hl=1 ER - TY - JFULL T1 - Central nervous system changes in hepatitis C virus infection. A1 - Forton, DM A1 - Taylor-Robinson, SD A1 - Thomas, HC J1 - Eur J Gastroenterol Hepatol Y1 - 2006/04// VL - 18 SN - 0954-691X SP - 333 EP - 338 N2 - Patients with chronic hepatitis C virus (HCV) infection frequently describe neuropsychological symptoms. Although hepatic encephalopathy is the best established neurological association of HCV infection, there is a growing body of literature on cerebral dysfunction, occurring at an early stage of chronic HCV infection, well before the development of cirrhosis. In this review we describe recent studies that have documented mild, but significant neurocognitive impairment in HCV infection. These deficits in patients with minimal or absent liver disease do not appear to be attributable to a history of substance abuse, coexistent depression or hepatic encephalopathy. Recent studies employing in-vivo magnetic resonance spectroscopy have suggested that a biological mechanism associated with the virus may be responsible. The hypothesis that HCV infection of the central nervous system may be related to the reported neuropsychological symptoms and cognitive impairment is supported by molecular virological studies of post-mortem brain tissue. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16538103&query_hl=1 ER - TY - JFULL T1 - Perinatal infections, prematurity and brain injury. A1 - Edwards, AD A1 - Tan, S J1 - Curr Opin Pediatr Y1 - 2006/04// VL - 18 SN - 1040-8703 SP - 119 EP - 124 N2 - PURPOSE OF REVIEW: The association between perinatal infection and brain injury is widely accepted but a cause-and-effect relationship has not yet been proven. This article summarizes available evidence and current primary publications for debate. RECENT FINDINGS: Work completed during the review period has reinforced current understanding of perinatal infection, prematurity and brain injury. In animal experiments: lipopolysaccharides have been further implicated in brain injury, not only as a cause of brain injury but also as mediators of preconditioning and protection. Recent studies suggest that cerebral injury following low-dose lipopolysaccharide administration may become compensated in adulthood. Other studies have emphasized the complexity of the response by showing that plasma cytokine levels may not reflect those in the central nervous system or inflammatory events in the brain. SUMMARY: Perinatal infection and maternofetal inflammation is strongly associated with preterm birth. Inflammation probably represents an important mechanism for cerebral damage, and both overt lesions and maldevelopment can result. Epidemiological data and multiple animal models to link infection, inflammation and brain damage exist, but proof of causation is elusive. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16601489&query_hl=1 ER - TY - JFULL T1 - Cell type-specific structural plasticity of axonal branches and boutons in the adult neocortex. A1 - De Paola, V A1 - Holtmaat, A A1 - Knott, G A1 - Song, S A1 - Wilbrecht, L A1 - Caroni, P A1 - Svoboda, K J1 - Neuron Y1 - 2006/03/16/ VL - 49 SN - 0896-6273 SP - 861 EP - 875 N2 - We imaged axons in layer (L) 1 of the mouse barrel cortex in vivo. Axons from thalamus and L2/3/5, or L6 pyramidal cells were identified based on their distinct morphologies. Their branching patterns and sizes were stable over times of months. However, axonal branches and boutons displayed cell type-specific rearrangements. Structural plasticity in thalamocortical afferents was mostly due to elongation and retraction of branches (range, 1-150 microm over 4 days; approximately 5% of total axonal length), while the majority of boutons persisted for up to 9 months (persistence over 1 month approximately 85%). In contrast, L6 axon terminaux boutons were highly plastic (persistence over 1 month approximately 40 %), and other intracortical axon boutons showed intermediate levels of plasticity. Retrospective electron microscopy revealed that new boutons make synapses. Our data suggest that structural plasticity of axonal branches and boutons contributes to the remodeling of specific functional circuits. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16543134&query_hl=1 ER - TY - JFULL T1 - Function of indoleamine 2,3-dioxygenase in corneal allograft rejection and prolongation of allograft survival by over-expression. A1 - Beutelspacher, SC A1 - Pillai, R A1 - Watson, MP A1 - Tan, PH A1 - Tsang, J A1 - McClure, MO A1 - George, AJ A1 - Larkin, DF J1 - Eur J Immunol Y1 - 2006/03// VL - 36 SN - 0014-2980 SP - 690 EP - 700 N2 - Indoleamine 2,3-dioxygenase (IDO) suppresses T cell responses by its action in catabolising tryptophan. It is important in maintenance of immune privilege in the placenta. We investigated the activity of IDO in the cornea, following corneal transplantation and the effect of IDO over-expression in donor corneal endothelium on the survival of corneal allografts. IDO expression was analysed and functional activity was quantified in normal murine cornea and in corneas following transplantation as allografts. Low levels of IDO, at both mRNA and protein levels, was detected in the normal cornea, up-regulated by IFN-gamma and TNF. Expression of IDO in cornea was significantly increased following corneal transplantation. However, inhibition of IDO activity in vivo had no effect on graft survival. Following IDO cDNA transfer, murine corneal endothelial cells expressed functional IDO, which was effective at inhibiting allogeneic T cell proliferation. Over-expression of IDO in donor corneal allografts resulted in prolonged graft survival. While, on one hand, our data indicate that IDO may augment corneal immune privilege, up-regulated IDO activity following cytokine stimulation may serve to inhibit inflammatory cellular responses. While increasing IDO mRNA expression was found in allogeneic corneas at rejection, over-expression in donor cornea was found to significantly extend survival of allografts. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16482510&query_hl=1 ER - TY - JFULL T1 - A major new initiative to improve treatment for children A1 - Smyth, RL A1 - Edwards, AD J1 - ARCH DIS CHILD Y1 - 2006/03// VL - 91 SN - 0003-9888 SP - 212 EP - 213 ER - TY - JFULL T1 - The role of positron emission tomography (PET) in the assessment of PSP A1 - Gerhard, A A1 - Brooks, DJ J1 - MOVEMENT DISORD Y1 - 2006/03// VL - 21 SN - 0885-3185 SP - 435 EP - 437 ER - TY - JFULL T1 - Smaller cerebellar volumes in very preterm infants at term-equivalent age are associated with the presence of supratentorial lesions. A1 - Srinivasan, L A1 - Allsop, J A1 - Counsell, SJ A1 - Boardman, JP A1 - Edwards, AD A1 - Rutherford, M J1 - AJNR Am J Neuroradiol Y1 - 2006/03// VL - 27 SN - 0195-6108 SP - 573 EP - 579 N2 - BACKGROUND AND PURPOSE: Traditionally cerebellar functions are thought to be related to control of tone, posture, gait, and coordination of skilled motor activity. However, there is an increasing body of evidence implicating the cerebellum in cognition, language, memory, and motor learning. Preterm infants are at increased risk of neurodevelopmental delay, cognitive dysfunction, and behavioral and emotional disturbances. The role of the cerebellum in these adverse outcomes is unclear. OBJECTIVE: The objective of this study was to determine whether absolute cerebellar volumes differ between term-equivalent preterm infants and term-born control infants and to assess whether cerebellar volume is influenced by any possible antenatal, perinatal, and postnatal factors. METHODS: The study compared the MR imaging cerebellar volume by using a manual quantification program of 113 preterm infants at term-equivalent age and 15 term-born control infants. RESULTS: The median cerebellar volume of preterm at term-equivalent age was 25.4 cm3 and that of term-born control infants was 26.9 cm3. On initial analysis, there was a significant median difference of 2.0 cm3 (95% CI, 1.2 cm3 to 2.7 cm3) (2-sided P < .0001). However multiple regression analysis of perinatal variables showed that only infants with supratentorial lesions (P = .003) were significantly associated with the reduction in cerebellar volumes. The median cerebellar volumes were the following: supratentorial lesions, 18.9 cm3; no supratentorial lesions, 26.1 cm3; and term infants, 26.9 cm3 (analysis of variance, P < .0001). Hence, there was no significant difference in cerebellar volumes of preterm infants at term-equivalent age in the absence of supratentorial lesions. The median vermal volumes were 0.7 cm3 and were significantly related to cerebellar volumes both in preterm infants with and without lesions and in term-control infants. CONCLUSION: Premature infants at term-equivalent age have similar total cerebellar and vermal volumes compared with term infants in the presence of normal brain imaging. Reduced cerebellar volume in preterm infants at term-equivalent age is seen in association with supratentorial pathology such as hemorrhagic parenchymal infarction, intraventricular hemorrhage with dilation, and periventricular leukomalacia. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16551994&query_hl=1 ER - TY - JFULL T1 - Randomized controlled trial of intraputamenal glial cell line-derived neurotrophic factor infusion in Parkinson disease A1 - Lang, AE A1 - Gill, S A1 - Patel, NK A1 - Lozano, A A1 - Nutt, JG A1 - Penn, R A1 - Brooks, DJ A1 - Hotton, G A1 - Moro, E A1 - Heywood, P A1 - Brodsky, MA A1 - Burchiel, K A1 - Kelly, P A1 - Dalvi, A A1 - Scott, B A1 - Stacy, M A1 - Turner, D A1 - Wooten, VGF A1 - Elias, WJ A1 - Laws, ER A1 - Dhawan, V A1 - Stoessl, AJ A1 - Matcham, J A1 - Coffey, RJ A1 - Traub, M J1 - ANN NEUROL Y1 - 2006/03// VL - 59 SN - 0364-5134 SP - 459 EP - 466 N2 - Objective: Glial cell line-derived neurotrophic factor (GDNF) exerts potent trophic influence on midbrain dopaminergic neurons. This randomized controlled clinical trial was designed to confirm initial clinical benefits observed in a small, open-label trial using intraputamenal (Ipu) infusion of recombinant human GDNF (liatermin). Metho Thirty-four PD patients were randomized 1 to 1 to receive bilateral continuous Ipu infusion of liatermin 15 mu g/putamen/day or placebo. The primary end point was the change in Unified Parkinson Disease Rating Scale (UPDRS) motor score in the practically defined off condition at 6 months. Secondary end points included other UPDRS scores, motor tests, dyskinesia ratings, patient diaries, and F-18-dopa uptake. Results: At 6 months, mean percentage changes in "off" UPDRS motor score were -10.0% and -4.5% in the liatermin and placebo groups, respectively. This treatment difference was not significant (95% confidence interval, -23.0 to 12.0, p = 0.53). Secondary end point results were similar between the groups. A 32.5% treatment difference favoring liatermin in mean F-18-dopa influx constant (p = 0.019) was observed. Serious, device-related adverse events required surgical repositioning of catheters in two patients and removal of devices in another. Neutralizing antiliatermin antibodies were detected in three patients (one on-study and two in the open-label extension). Interpretation: Liatermin did not confer the predetermined level of clinical benefit to patients with PD despite increased 18 F-dopa uptake. It is uncertain whether technical differences between this trial and positive open-label studies contributed in any way this negative outcome. ER - TY - JFULL T1 - Effect of vectors on human endothelial cell signal transduction: implications for cardiovascular gene therapy. A1 - Tan, PH A1 - Xue, SA A1 - Manunta, M A1 - Beutelspacher, SC A1 - Fazekasova, H A1 - Alam, AK A1 - McClure, MO A1 - George, AJ J1 - Arterioscler Thromb Vasc Biol Y1 - 2006/03// VL - 26 SN - 1524-4636 SP - 462 EP - 467 N2 - OBJECTIVE: Endothelium is an important target for gene therapy. We have investigated the effect of viral and nonviral vectors on the phenotype and function of endothelial cells (ECs) and developed methods to block any activation caused by these vectors. METHODS AND RESULTS: Transduction of ECs with viral vectors, including adenovirus, lentiviruses, and Moloney murine leukemia virus, can induce a pro-inflammatory phenotype. This activation was reduced when nonviral vectors were used. We demonstrate that after transduction there is upregulation of dsRNA-triggered antiviral and PI3K/Akt signaling pathway. Blockade of the NFkappaB, PI3-K, or PKR signaling pathways all operated to inhibit partially virally induced activation, and inhibition of both PKR and PI3-K pathways totally blocked EC activation. Furthermore, inhibition of IFN-alpha/beta in addition to PI3-K was effective at preventing EC activation. CONCLUSIONS: Viral vectors, although efficient at transducing ECs, result in their activation. Blockade of the signaling pathways involved in viral activation may be used to prevent such activation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16357316&query_hl=1 ER - TY - JFULL T1 - Therapeutic hypothermia following perinatal asphyxia. A1 - Edwards, AD A1 - Azzopardi, DV J1 - Arch Dis Child Fetal Neonatal Ed Y1 - 2006/03// VL - 91 SN - 1359-2998 SP - F127 EP - F131 N2 - Well constructed and carefully analysed trials of hypothermic neural rescue therapy for infants with neonatal encephalopathy have recently been reported. The data suggest that either selective head cooling or total body cooling reduces the combined chance of death or disability after birth asphyxia. However, as there are still unanswered questions about these treatments, many may still feel that further data are needed before health care policy can be changed to make cooling the standard of care for all babies with suspected birth asphyxia. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16492950&query_hl=1 ER - TY - JFULL T1 - Nigral degeneration and striatal dopaminergic dysfunction in idiopathic and Parkin-linked Parkinson's disease. A1 - Hu, MT A1 - Scherfler, C A1 - Khan, NL A1 - Hajnal, JV A1 - Lees, AJ A1 - Quinn, N A1 - Wood, NW A1 - Brooks, DJ J1 - Mov Disord Y1 - 2006/03// VL - 21 SN - 0885-3185 SP - 299 EP - 305 N2 - We have used MR segmented inversion recovery ratio imaging (SIRRIM) of the substantia nigra pars compacta to detect and correlate nigral signal change in idiopathic Parkinson's disease (PD) and parkin patients with striatal (18)F-dopa uptake. Nine PD patients, nine parkin patients, and eight control subjects were studied with a combination of MR inversion recovery sequences sensitive to nigral cell loss. Blinded independent observer rating and quantified nigral signal analysis were performed on all subjects. Striatal regions of interest were defined on T(1)-weighted MRI co-registered to (18)F-dopa positron emission tomography. On blinded observer rating of the SIRRIM dorsal and ventral nigral images, 25% (2/8) of control subjects, 44% (4/9) of PD patients, and 67% (6/9) of parkin patients were classified as abnormal. Quantified total nigral signal intensities were reduced to a greater extent in the parkin compared to PD patients. There was a greater predilection for signal reduction in the ventral nigral slice of the PD compared to the parkin patient group, who showed a more uniform involvement. All PD and parkin patients were discriminated from controls on the basis of caudate and putamen (18)F-dopa Ki reductions. Our results suggest that MR segmented inversion recovery ratio imaging shows poor sensitivity for discriminating parkin and idiopathic PD patients from normal controls. Where nigral signal abnormalities were seen, parkin patients manifested generalized nigral cell loss with widespread striatal dopamine terminal dysfunction compared with the lateral nigral targeting seen in PD and selective loss of putamen (18)F-dopa uptake. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16211589&query_hl=1 ER - TY - JFULL T1 - Contrast echocardiography versus gated single photon emission computed tomography for the assessment of parameters of left ventricular remodeling after acute myocardial infarction A1 - Lim, TK A1 - Burden, L A1 - Janardhanan, R A1 - Dwivedi, G A1 - Ping, C A1 - Moon, J A1 - Pennell, DJ A1 - Senior, R J1 - J AM SOC ECHOCARDIOG Y1 - 2006/03// VL - 19 SN - 0894-7317 SP - 280 EP - 284 N2 - Background: Assessment of parameters of left ventricular (LV) remodeling after acute myocardial infarction (AMI) has both therapeutic and prognostic implication. Contrast echocardiography (CE) has the advantage of simultaneously assessing myocardial perfusion and LV remodeling. We aimed to evaluate the accuracy of CE to assess LV remodeling after AMI compared with technetium-99m sestamibi gated single photon emission computed tomography (SPECT).Methods: Accordingly, 36 consecutive patients underwent gated SPECT, CE, and cardiovascular magnetic resonance imaging (CMR) 7 to 10 days after AMI. LV ejection fraction (LVEF), and LV end-systolic and end-diastolic volumes were assessed.Results: Absolute differences for LVEF and LV end-diastolic volume between CMR and CE were significantly smaller than that between CMR and SPECT. CE estimate of LVEF more accurately classified patients into LVEF less than 35%, 35% to 45%, and greater than 45% (agreement = 83%, kappa = 0.66 with CMR) compared with SPECT (agreement 61%, kappa = 0.36 with CMR).Conclusion: CE is more accurate than gated SPECT for the estimation of LV remodeling after AMI. ER - TY - JFULL T1 - Segmental mediolytic arteriopathy in a patient with intraperitoneal bleeding. A1 - Rosenfelder, NA A1 - Taylor-Robinson, SD A1 - Jackson, JE A1 - Stamp, GW J1 - Eur J Gastroenterol Hepatol Y1 - 2006/03// VL - 18 SN - 0954-691X SP - 295 EP - 297 N2 - Segmental mediolytic arteriopathy (SMA) is a rare condition. It was first defined in 1976 and has been well described in the literature, although to date the aetiology of the condition is unknown. In most case reports SMA is diagnosed retrospectively once tissue has undergone histological examination. We present the first known case of SMA of the colic, mid-jejunal, common hepatic, intrahepatic and gastric arteries to be diagnosed at angiography after multiple episodes of undiagnosed intraperitoneal bleeding, and, perhaps related to this, one of the few reported patients with SMA involving multiple intra-abdominal arteries to have survived. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16462545&query_hl=1 ER - TY - JFULL T1 - Imaging glutamate neurotransmission using PET and SPECT A1 - Hammers, A J1 - EPILEPSIA Y1 - 2006/03// VL - 47 SN - 0013-9580 SP - 268 EP - 268 ER - TY - JFULL T1 - Technical report: Magnetic resonance direct thrombus imaging at 3 T field strength in patients with lower limb deep vein thrombosis: a feasibility study. A1 - Schmitz, SA A1 - O'Regan, DP A1 - Gibson, D A1 - Cunningham, C A1 - Fitzpatrick, J A1 - Allsop, J A1 - Larkman, DJ A1 - Hajnal, JV J1 - Clin Radiol Y1 - 2006/03// VL - 61 SN - 0009-9260 SP - 282 EP - 286 N2 - AIM: To investigate the feasibility of imaging lower limb deep vein thrombosis using magnetic resonance imaging (MRI) at 3.0 T magnetic field strength with an optimized a T1 magnetization prepared rapid gradient echo technique (MP-RAGE) in patients with normal volunteers as controls. MATERIALS AND METHODS: Patients with deep vein thrombosis (n = 4), thrombophlebitis (n = 2) and healthy volunteers (n = 9) were studied. MRI of the distal thigh and upper calf was performed at 3.0 T with MP-RAGE using two pre-pulses to suppress blood and fat (flip angle 15 degrees, echo time 5 ms, and repetition time 10 ms). A qualitative analysis was performed for detection of thrombi and image quality. Contrast-to-noise ratios were determined in thrombosed and patent veins. RESULTS: Thrombi were clearly visible as high-signal intensity structures with good suppression of the anatomical background. A blinded reader accurately diagnosed 15 out of 16 cases. The contrast-to-noise ratio measurements showed a positive contrast of thrombus over background muscle 16.9 (SD 4.3, 95% CI: 12.5-21.3) and a negative contrast of the lumen to muscle in patent veins of normal volunteers -7.8 (SD 4.3, 95% CI: -11.1 to -4.5), with p = 0.0015. CONCLUSION: Thrombi generate high signal intensity at 3.0 T allowing for their direct visualization if flowing blood, stationary blood and fat are sufficiently suppressed. This preliminary data supports the development of these techniques for other vascular applications. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16488211&query_hl=1 ER - TY - JFULL T1 - GDNF in treatment of Parkinson's disease: response to editorial A1 - Lang, AE A1 - Langston, W A1 - Stoess, AJ A1 - Brodsky, M A1 - Brooks, DJ A1 - Dhawan, V A1 - Elias, WJ A1 - Lozano, AM A1 - Moro, E A1 - Nutt, JG A1 - Stacy, M A1 - Turner, D A1 - Wooten, GF J1 - LANCET NEUROL Y1 - 2006/03// VL - 5 SN - 1474-4422 SP - 200 EP - 202 ER - TY - JFULL T1 - Diffusion tensor and magnetisation transfer imaging of the brain at 3T in patients with cirrhosis and hepatic encephalopathy A1 - Grover, VP A1 - Counsell, SJ A1 - Forton, DM A1 - Bradford, EJ A1 - Saxby, BK A1 - Thomas, HC A1 - Hajnal, JV A1 - Taylor-Robinson, SD J1 - J HEPATOL Y1 - 2006/02// VL - 44 SN - 0168-8278 SP - S75 EP - S76 ER - TY - JFULL T1 - Axial and radial diffusivity in preterm infants who have diffuse white matter changes on magnetic resonance imaging at term-equivalent age. A1 - Counsell, SJ A1 - Shen, Y A1 - Boardman, JP A1 - Larkman, DJ A1 - Kapellou, O A1 - Ward, P A1 - Allsop, JM A1 - Cowan, FM A1 - Hajnal, JV A1 - Edwards, AD A1 - Rutherford, MA J1 - Pediatrics Y1 - 2006/02// VL - 117 SN - 1098-4275 SP - 376 EP - 386 N2 - OBJECTIVE: Diffuse excessive high signal intensity (DEHSI) is observed in the majority of preterm infants at term-equivalent age on conventional MRI, and diffusion-weighted imaging has shown that apparent diffusion coefficient values are elevated in the white matter (WM) in DEHSI. Our aim was to obtain diffusion tensor imaging on preterm infants at term-equivalent age and term control infants to test the hypothesis that radial diffusivity was significantly different in the WM in preterm infants with DEHSI compared with both preterm infants with normal-appearing WM on conventional MRI and term control infants. METHODS: Diffusion tensor imaging was obtained on 38 preterm infants at term-equivalent age and 8 term control infants. Values for axial (lambda1) and radial [(lambda2 + lambda3)/2] diffusivity were calculated in regions of interest positioned in the central WM at the level of the centrum semiovale, frontal WM, posterior periventricular WM, occipital WM, anterior and posterior portions of the posterior limb of the internal capsule, and the genu and splenium of the corpus callosum. RESULTS: Radial diffusivity was elevated significantly in the posterior portion of the posterior limb of the internal capsule and the splenium of the corpus callosum, and both axial and radial diffusivity were elevated significantly in the WM at the level of the centrum semiovale, the frontal WM, the periventricular WM, and the occipital WM in preterm infants with DEHSI compared with preterm infants with normal-appearing WM and term control infants. There was no significant difference between term control infants and preterm infants with normal-appearing WM in any region studied. CONCLUSIONS: These findings suggest that DEHSI represents an oligodendrocyte and/or axonal abnormality that is widespread throughout the cerebral WM. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16452356&query_hl=1 ER - TY - JFULL T1 - Hypothermia and perinatal asphyxia: executive summary of the National Institute of Child Health and Human Development workshop. A1 - Higgins, RD A1 - Raju, TN A1 - Perlman, J A1 - Azzopardi, DV A1 - Blackmon, LR A1 - Clark, RH A1 - Edwards, AD A1 - Ferriero, DM A1 - Gluckman, PD A1 - Gunn, AJ A1 - Jacobs, SE A1 - Eicher, DJ A1 - Jobe, AH A1 - Laptook, AR A1 - LeBlanc, MH A1 - Palmer, C A1 - Shankaran, S A1 - Soll, RF A1 - Stark, AR A1 - Thoresen, M A1 - Wyatt, J J1 - J Pediatr Y1 - 2006/02// VL - 148 SN - 0022-3476 SP - 170 EP - 175 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16492424&query_hl=1 ER - TY - JFULL T1 - Variation in the lipoprotein lipase gene influences exercise-induced left ventricular growth A1 - Flavell, DM A1 - Wootton, PTE A1 - Myerson, SG A1 - World, MJ A1 - Pennell, DJ A1 - Humphries, SE A1 - Talmud, PJ A1 - Montgomery, HE J1 - J MOL MED-JMM Y1 - 2006/02// VL - 84 SN - 0946-2716 SP - 126 EP - 131 N2 - The adult heart relies predominantly on fatty acids (FA) for energy generation, and defects in FA catabolism cause dramatic left ventricular (LV) growth in early age. Since lipoprotein lipase (LPL) is the key enzyme in plasma triglyceride catabolism and is highly expressed in the myocardium, we investigated an association between the functional LPL gene serine 447 stop (S447X) variant and exercise-induced LV growth. The S447X variant was genotyped in 146 British Army recruits undergoing a 10-week exercise programme. Over the training period, X447 allele carriers showed less LV growth than S447 homozygotes (SS, 5.8 +/- 0.7%; SX, 2.2 +/- 1.5%; P=0.03) and a decrease in systolic blood pressure (Delta SBP: SS, 1.9 +/- 1.3 mmHg; SX, -5.7 +/- 2.2 mmHg; P=0.015). Although LPL genotype did not significantly predict LV growth with Delta SBP in statistical modelling (LPL, P=0.14; Delta SBP, P=0.06), regression analysis indicated that LPL S447X genotype effect on Delta SBP accounted for only 20% of the effect on LV growth. In multivariate analysis, LPL, peroxisome-proliferator-activated receptor alpha and angiotensin-converting enzyme genotypes were independent predictors of cardiac growth. Thus, LPL S447X genotype influenced exercise-induced changes in LV mass and SBP. Change in blood pressure accounted for a proportion of LV growth. These data suggest that increased myocardial FA availability may reduce exercise-induced LV growth. ER - TY - JFULL T1 - Supervised reference region extraction for the quantification of [11C]-(R)-PK11195 brain studies A1 - Turkheimer, FE A1 - Edison, P A1 - Pavese, N A1 - Roncaroli, F A1 - Hammers, A A1 - Gerhard, A A1 - Hinz, R A1 - Tai, YF A1 - Brooks, DJ J1 - NEUROIMAGE Y1 - 2006/02// VL - 31 SN - 1053-8119 SP - T18 EP - T18 ER - TY - JFULL T1 - In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson's disease. A1 - Gerhard, A A1 - Pavese, N A1 - Hotton, G A1 - Turkheimer, F A1 - Es, M A1 - Hammers, A A1 - Eggert, K A1 - Oertel, W A1 - Banati, RB A1 - Brooks, DJ J1 - Neurobiol Dis Y1 - 2006/02// VL - 21 SN - 0969-9961 SP - 404 EP - 412 N2 - Idiopathic Parkinson's disease (PD) is a neurodegenerative disorder associated with akinesia, tremor and rigidity. While the characteristic Lewy body pathology targets pigmented and other brainstem nuclei at post-mortem, activated microglia are found in both subcortical and cortical areas. [11C](R)-PK11195 is a positron emission tomography (PET) marker of peripheral benzodiazepine sites (PBBS), which are selectively expressed by activated microglia. We examined 18 PD patients clinically and with [11C](R)-PK11195 and [18F]-dopa PET. Compared to 11 normal controls, the PD patients showed significantly increased mean levels of [11C](R)-PK11195 binding in the pons, basal ganglia and frontal and temporal cortical regions. Eight PD patients were examined longitudinally, and their [11C](R)-PK11195 signal remained stable over 2 years. Levels of microglial activation did not correlate with clinical severity or putamen [18F]-dopa uptake. Our in vivo findings confirm that widespread microglial activation is associated with the pathological process in PD. The absence of significant longitudinal changes suggests that microglia are activated early in the disease process, and levels then remain relatively static, possibly driving the disease via cytokine release. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16182554&query_hl=1 ER - TY - JFULL T1 - Ventricular fibrosis suggested by cardiovascular magnetic resonance in adults with repaired tetralogy of fallot and its relationship to adverse markers of clinical outcome. A1 - Babu-Narayan, SV A1 - Kilner, PJ A1 - Li, W A1 - Moon, JC A1 - Goktekin, O A1 - Davlouros, PA A1 - Khan, M A1 - Ho, SY A1 - Pennell, DJ A1 - Gatzoulis, MA J1 - Circulation Y1 - 2006/01/24/ VL - 113 SN - 1524-4539 SP - 405 EP - 413 N2 - BACKGROUND: Late morbidity and mortality remain problematic after repair of tetralogy of Fallot (TOF). We hypothesized that fibrosis detected by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) would be present in adults with repaired TOF and would be related to adverse markers of outcome. METHOD AND RESULTS: LGE was scored in the right and left ventricles (RV and LV) of 92 adult patients who had undergone TOF repair. RV LGE was seen in all patients at surgical sites located in the outflow tract (99%) or the site of ventricular septal defect patching (98%) and in the inferior RV insertion point (79%) and trabeculated myocardium (24%). LV LGE (53%) was located at the apex consistent with apical vent insertion (49%), in the inferior or lateral wall consistent with infarction (5%), or in other areas (8%). Patients with supramedian RV LGE score were older (38 versus 27 years, P<0.001) and more symptomatic (38% versus 8% in New York Heart Association class II or greater, P=0.001), had increased levels of atrial natriuretic peptide (7.3 versus 4.9 pmol/L, P=0.041), and had a trend to higher brain natriuretic peptide (12.3 versus 7.2 pmol/L, P=0.086), exercise intolerance (maximum VO2 24 versus 28 mL.min(-1).kg(-1), P=0.021), RV dysfunction (RV end-systolic volume 61 versus 55 mL/m2, P=0.018; RV ejection fraction 50% versus 56%, P=0.007), and clinical arrhythmia (26% versus 10%, P=0.039). Non-apical vent LV LGE also correlated with markers of adverse outcome. In a multivariate model, RV LGE remained a predictor of arrhythmia. CONCLUSIONS: RV and LV LGE were common after TOF repair and were related to adverse clinical markers, including ventricular dysfunction, exercise intolerance, and neurohormonal activation. Furthermore, RV LGE was significantly associated with clinical arrhythmia. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16432072&query_hl=1 ER - TY - JFULL T1 - Long-term live imaging of neuronal circuits in organotypic hippocampal slice cultures. A1 - Gogolla, N A1 - Galimberti, I A1 - DePaola, V A1 - Caroni, P J1 - Nat Protoc Y1 - 2006/// VL - 1 SN - 1750-2799 SP - 1223 EP - 1226 N2 - This protocol details a method for imaging organotypic slice cultures from the mouse hippocampus. The cultures are based on the interface method, which does not require special equipment, is easy to execute, and yields slice cultures that can be imaged repeatedly after they are isolated on postnatal day 6-9 and for up to 6 months in vitro. The preserved tissue architecture facilitates the analysis of defined hippocampal synapses, cells and entire projections. Time-lapse imaging is based on transgenes expressed in the mice, or on constructs introduced through transfection or viral vectors; it can reveal processes that develop over time periods ranging from seconds to months. Imaging can be repeated at least eight times without detectable morphological damage to neurons. Subsequent to imaging, the slices can be processed for immunocytochemistry or electron microscopy, to collect further information about the structures that have been imaged. This protocol can be completed in 35 min. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17406405&query_hl=1 ER - TY - JFULL T1 - The histological basis of late gadolinium enhancement cardiovascular magnetic resonance in a patient with Anderson-Fabry disease. A1 - Moon, JC A1 - Sheppard, M A1 - Reed, E A1 - Lee, P A1 - Elliott, PM A1 - Pennell, DJ J1 - J Cardiovasc Magn Reson Y1 - 2006/// VL - 8 SN - 1097-6647 SP - 479 EP - 482 N2 - Anderson-Fabry Disease (AFD) is a storage disease that mimics hypertrophic cardiomyopathy. Late gadolinium enhancement (LGE) by cardiovascular magnetic resonance occurs in approximately 50% of patients in the basal inferolateral LV wall, but how an intracellular storage disease causes focal LGE is unknown. We present a whole-heart histological validation that LGE is caused by focal myocardial collagen scarring. This scarring may be the substrate for electrical re-entry and sudden arrhythmic death. The reasons for this distribution of fibrosis are unclear, but may reflect inhomogeneous left ventricular wall stress. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16755835&query_hl=1 ER - TY - JFULL T1 - Congenital Cardiovascular Applications of Biomechanics A1 - Kilner PJ J1 - 5th World Congress of Biomechanics Y1 - 2006/// PB - Medimond SP - 419 EP - 424 UR - http://www.medimond.com/proceedings/moreinfo/20060729.htm ER - TY - JFULL T1 - Beyond the g-factor limit in sensitivity encoding using joint histogram entropy. A1 - Larkman, DJ A1 - Batchelor, PG A1 - Atkinson, D A1 - Rueckert, D A1 - Hajnal, JV J1 - Magn Reson Med Y1 - 2006/01// VL - 55 SN - 0740-3194 SP - 153 EP - 160 N2 - The maximum practical speed-up that can be achieved using parallel imaging methods is widely accepted to be limited by g-factor noise. An approximate expression for the g-factor noise as a function of the principal eigenvector of the inverse sensitivity matrix is derived. This formulation allows g-factor enhanced noise to be reduced by a constrained optimization procedure with joint image histogram entropy between a reference image and a SENSE image as an image quality metric. The reference image does not need to have identical resolution or contrast. The reference image may also be used for coil calibration. The limits of the method are explored using simulated and real array coil data with high g-factor using a variety of contrast and resolution combinations. The method preserves image structure, contrast, and lesions even when these were not observable in the reference data. In all cases g-factor was dramatically reduced. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16342149&query_hl=1 ER - TY - JFULL T1 - Segmentation of brain MRI in young children. A1 - Murgasova, M A1 - Dyet, L A1 - Edwards, D A1 - Rutherford, M A1 - Hajnal, JV A1 - Rueckert, D J1 - Med Image Comput Comput Assist Interv Int Conf Med Image Comput Comput Assist Interv Y1 - 2006/// VL - 9 SP - 687 EP - 694 N2 - This paper describes an automatic tissue segmentation algorithm for brain MRI of young children. Existing segmentation methods developed for the adult brain do not take into account the specific tissue properties present in the brain MRI of young children. We examine the suitability of state-of-the-art methods developed for the adult brain when applied to the segmentation of the young child brain MRI. We develop a method of creation of a population-specific atlas from young children using a single manual segmentation. The method is based on non-linear propagation of the segmentation into population and subsequent affine alignment into a reference space and averaging. Using this approach we significantly improve the performance of the popular EM segmentation algorithm on brain MRI of young children. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17354950&query_hl=1 ER - TY - JFULL T1 - Staining protocol for organotypic hippocampal slice cultures. A1 - Gogolla, N A1 - Galimberti, I A1 - DePaola, V A1 - Caroni, P J1 - Nat Protoc Y1 - 2006/// VL - 1 SN - 1750-2799 SP - 2452 EP - 2456 N2 - This protocol details a method to immunostain organotypic slice cultures from mouse hippocampus. The cultures are based on the interface method, which does not require special equipment, is easy to execute and yields slice cultures that can be imaged repeatedly, from the time of isolation at postnatal day 6-9 up to 6 months in vitro. The preserved tissue architecture facilitates the analysis of defined hippocampal synapses, cells and entire projections. Time-lapse imaging is based on transgenes expressed in the mice or on constructs introduced through transfection or viral vectors; it can reveal processes that develop over periods ranging from seconds to months. Subsequent to imaging, the slices can be processed for immunocytochemistry to collect further information about the imaged structures. This protocol can be completed in 3 d. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17406491&query_hl=1 ER - TY - JFULL T1 - Primary myocardial dysfunction in autosomal dominant EDMD. A tissue doppler and cardiovascular magnetic resonance study. A1 - Smith, GC A1 - Kinali, M A1 - Prasad, SK A1 - Bonne, G A1 - Muntoni, F A1 - Pennell, DJ A1 - Nihoyannopoulos, P J1 - J Cardiovasc Magn Reson Y1 - 2006/// VL - 8 SN - 1097-6647 SP - 723 EP - 730 N2 - BACKGROUND: Emery-Dreifuss muscular dystrophy is a genetically heterogeneous form of muscular dystrophy. One form is inherited in an X-linked fashion and is secondary to mutations in the gene encoding the nuclear protein emerin. A more common variant is inherited in an autosomal dominant way (EDMD2) due to mutations affecting the nuclear lamina protein lamin A/C. Typical features of both conditions are relatively mild skeletal muscle weakness, but cardiac involvement develops almost invariably by adult age, including conduction defects, arrhythmias and cardiomyopathy. Thus, early detection of cardiac abnormalities may be important for planning early therapeutic intervention. AIM: In this study, we hypothesized that early myocardial dysfunction can be detected by tissue Doppler echocardiography and CMR in unselected patients with the autosomal dominant form of Emery-Dreifuss muscular dystrophy. This would suggest that fibrosis could be implicated in the pathogenesis of cardiac dysfunction in EDMD2. METHODS: Eight consecutive patients with genetically proven EDMD2 without pacemakers were enrolled in the study and compared to eight age-matched controls. All patients and controls first underwent a comprehensive echocardiographic-Doppler examination, followed by measurement of mitral annular velocities using pulsed tissue Doppler. Color M-mode tissue images were recorded from the parasternal long axis projections to derive Myocardial Velocity Gradients (MVG). Subsequently, all subjects underwent cardiovascular magnetic resonance (CMR) imaging for function, intrinsic myocardial tissue contrast using T1 and T2 weighted spin echo (TSE) for fat deposition and extrinsic contrast (Gadolinium-DTPA late fibrosis imaging). Strain measurements, using harmonic phase imaging (HARP) tagging were also derived. RESULTS: Cavity dimensions LV mass and fractional shortening were similar between patients and controls. The overall body mass index was less in patients than in controls (14.5 +/- 1.4 vs. 18.1 +/- 2.4 g/m2, p < 0.002). While systolic MVG were similar between groups, the early diastolic MVG was lower in patients than in controls (4 +/- 1.2 s-1 vs. 7.1 +/- 2.7, p < 0.02). On CMR, LA and LV, RV volumes were similar between patients and controls. CMR strain patterns, however, showed a significant reduction in inferior wall contractility in patients compared to controls (-0.06 +/- 0.02 vs -0.09 +/- 0.03, p < 0.05). No patient showed late gadolinium enhancement. CONCLUSION: Patients with EDMD2 have abnormal left ventricular function prior to developing any cardiac symptoms. The absence of myocardial fibrosis, however, by CMR suggests that this functional abnormality may not be secondary to scarring but could precede it. Tissue Doppler echocardiography and CMR are sensitive methods of assessing the presence of myocardial dysfunction prior to the development of any cardiovascular symptoms. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16891232&query_hl=1 ER - TY - JFULL T1 - Local mesh adaptation for soft tissue simulation A1 - Paloc, C A1 - Faraci, A A1 - Bello, F J1 - LECT NOTES COMPUT SC Y1 - 2006/// VL - 4072 SN - 0302-9743 SP - 206 EP - 214 N2 - This paper addresses the problem of graphically modelling the realistic behaviour of deformable tissue that can undergo structural modifications. Building on traditional modelling methods, we propose the online remeshing of a volumetric deformable model for locally adapting the underlying mesh and thus optimising the computational workload. Our technique overcomes limitations of previous methods that made it difficult to modify the topology of the mesh online. The performance of our methodology is demonstrated for each of the two main tissue modelling methods: mass-spring systems and finite element methods. ER - TY - JFULL T1 - Preparation of organotypic hippocampal slice cultures for long-term live imaging. A1 - Gogolla, N A1 - Galimberti, I A1 - DePaola, V A1 - Caroni, P J1 - Nat Protoc Y1 - 2006/// VL - 1 SN - 1750-2799 SP - 1165 EP - 1171 N2 - This protocol details a method to establish organotypic slice cultures from mouse hippocampus, which can be maintained for several months. The cultures are based on the interface method, which does not require special equipment, is easy to execute and yields slice cultures that can be imaged repeatedly--from when they are isolated at postnatal day 6-9, and up to 6 months in vitro. The preserved tissue architecture facilitates the analysis of defined hippocampal synapses, cells and entire projections. Monitoring of defined cellular and molecular components in the slices can be achieved by preparing slices from transgenic mice or by introducing transgenes through transfection or viral vectors. This protocol can be completed in 3 h. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17406399&query_hl=1 ER - TY - JFULL T1 - Normalized left ventricular systolic and diastolic function by steady state free precession cardiovascular magnetic resonance. A1 - Maceira, AM A1 - Prasad, SK A1 - Khan, M A1 - Pennell, DJ J1 - J Cardiovasc Magn Reson Y1 - 2006/// VL - 8 SN - 1097-6647 SP - 417 EP - 426 N2 - We used state of the art CMR to define ranges for normal left ventricular volumes and systolic/diastolic function normalized to the influence of gender, body surface area and age. New CMR normalized ranges were modeled and displayed in graphical form for clinical use, with normalization for body surface area, gender, and age. The determination of normality, or the severity of abnormality, depends on the use of the appropriate reference ranges normalized to all 3 variables. These novel data have particular importance for clinical practice and clinical trials using CMR. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16755827&query_hl=1 ER - TY - JFULL T1 - Development of thalassaemic iron overload cardiomyopathy despite low liver iron levels and meticulous compliance to desferrioxamine. A1 - Anderson, LJ A1 - Westwood, MA A1 - Prescott, E A1 - Walker, JM A1 - Pennell, DJ A1 - Wonke, B J1 - Acta Haematol Y1 - 2006/// VL - 115 SN - 0001-5792 SP - 106 EP - 108 N2 - It is believed that myocardial iron deposition and the resultant cardiomyopathy only occur in the presence of severe liver iron overload. Using cardiovascular magnetic resonance, it is now possible to assess myocardial and liver iron levels as well as cardiac function in the same scan, allowing this supposition to be examined. We describe a patient with progressive myocardial iron deposition and the development of early iron overload cardiomyopathy despite excellent compliance to standard subcutaneous desferrioxamine, minimal liver iron and well-controlled serum ferritin levels. These indirect markers remained far below the thresholds conventionally believed to be associated with increased cardiac risk. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16424659&query_hl=1 ER - TY - JFULL T1 - Simulating tele-manipulator controlled tool-tissue interactions using a nonlinear FEM deformable model. A1 - Wang, DA A1 - Faraci, A A1 - Bello, F A1 - Darzi, A J1 - Stud Health Technol Inform Y1 - 2006/// VL - 119 SN - 0926-9630 SP - 565 EP - 567 N2 - Enhanced visualization of an operating scene presented by a robotically assisted tele-manipulator system such as the da Vinci(TM) can be provided through the use of augmented reality facilities. Generating overlays from 3D models and the intra-operative video allows the surgeon to acquire greater information about the surgical scene. Tool-tissue interactions must be tracked to ensure the overlays are updated regularly and accurately. The work presented here describes how these interactions may be modelled by integrating a nonlinear finite element model with the 3D reconstruction and using the tool kinematic data as input to the deformation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16404122&query_hl=1 ER - TY - JFULL T1 - Distributed neural actions of anti-parkinsonian therapies as revealed by PET. A1 - Goerendt, IK A1 - Lawrence, AD A1 - Mehta, MA A1 - Stern, JS A1 - Odin, P A1 - Brooks, DJ J1 - J Neural Transm Y1 - 2006/01// VL - 113 SN - 0300-9564 SP - 75 EP - 86 N2 - There is a limited understanding of how different anti-parkinsonian treatments act at the neuronal systems level. Using positron emission tomography we examined the effects of levodopa and deep brain stimulation of the subthalamic nucleus on patterns of regional cerebral blood flow in patients with Parkinson's disease during a homogenous cognitive-behavioural state rather than during an unspecified resting state. We found that when medicated precuneus, frontal, parietal, cerebellar and midbrain areas were relatively more activated than when stimulated, whereas when stimulated the precentral gyrus, caudate and thalamus were relatively more activated than when medicated. Areas that were activated by both treatments included the temporal gyri, anterior thalamus, and midbrain. Regions of prefrontal cortex showed relatively greater activation in the "off treatment" conditions of both the medicated and stimulated groups. Our findings suggest that the two treatment methods may lead to symptomatic relief via both common and different sites of action. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16049638&query_hl=1 ER - TY - JFULL T1 - The use of a GripForce system to map force distribution patterns of laparoscopic instruments. A1 - Gupta, N A1 - Bello, F A1 - Arnarsson, H A1 - Riviere, P A1 - Hoult, S A1 - Darzi, A J1 - Stud Health Technol Inform Y1 - 2006/// VL - 119 SN - 0926-9630 SP - 170 EP - 175 N2 - While it is acknowledged that the forces required to manipulate laparoscopic instruments can be significant and are important in terms of potential discomfort after prolonged use, no systematic study has been conducted. In this paper we present a GripForce system that allows for the mapping of force distribution patterns of laparoscopic instruments. Initial results showed significant differences in force distribution between various instrument handles, thus demonstrating the viability of the system and proposed methodology. Analysis of force distribution patterns of laparoscopic instruments can help towards improving instrument design, better understanding the relationship between force applied and performance, as well as provide useful feedback to trainees and surgeons. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16404039&query_hl=1 ER - TY - JFULL T1 - Myocardial iron loading in patients with thalassemia major on deferoxamine chelation. A1 - Tanner, MA A1 - Galanello, R A1 - Dessi, C A1 - Westwood, MA A1 - Smith, GC A1 - Nair, SV A1 - Anderson, LJ A1 - Walker, JM A1 - Pennell, DJ J1 - J Cardiovasc Magn Reson Y1 - 2006/// VL - 8 SN - 1097-6647 SP - 543 EP - 547 N2 - BACKGROUND: Heart failure secondary to myocardial iron loading remains the leading cause of death in thalassemia major (TM). We used cardiovascular magnetic resonance (CMR) to assess the prevalence of myocardial iron overload and ventricular dysfunction in a large cohort of TM patients maintained on conventional chelation treatment with deferoxamine. METHODS: A mobile CMR scanner was transported from London, UK, to Sardinia, Italy where 167 TM patients were assessed for myocardial iron loading, B-natriuretic peptide (BNP), and ferritin. In patients with myocardial iron loading CMR assessments of ventricular function were also made. RESULTS: Myocardial iron loading (T2* < 20 ms) was present in 108 (65%) patients, which was severe (T2* < 8 ms) in 22 (13%). Impaired (< 56%) left ventricular (LV) ejection fraction (EF) was present in 5%, 20% and 62% of patients with mild, moderate or severe iron loading. Increasing myocardial iron was related to impaired LVEF (Rs = 0.57, p < 0.001), weakly related to serum ferritin (Rs = -0.34, p < 0.001), and not related to liver iron (Rs = 0.11, p = 0.26). BNP was weakly related to myocardial iron (Rs = -0.35, p < 0.001) and was abnormal in only 5 patients. CONCLUSIONS: Myocardial siderosis was found in two-thirds of thalassemia major patients on maintenance deferoxamine treatment. This was combined with a high prevalence of impaired LV function, the severity of which tracked the severity of iron deposition. BNP was not useful to assess myocardial siderosis. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16755844&query_hl=1 ER - TY - JFULL T1 - Principles and applications of computer graphics in medicine A1 - Vidal, FP A1 - Bello, F A1 - Brodlie, KW A1 - John, NW A1 - Gould, D A1 - Phillips, R A1 - Avis, NJ A1 - Hirsch, T J1 - COMPUT GRAPH FORUM Y1 - 2006/// VL - 25 SN - 0167-7055 SP - 113 EP - 137 N2 - The medical domain provides excellent opportunities for the application of computer graphics, visualization and virtual environments, with the potential to help improve healthcare and bring benefits to patients. This survey paper provides a comprehensive overview of the state-of-the-art in this exciting field. It has been written from the perspective of both computer scientists and practising clinicians and documents past and current successes together with the challenges that lie ahead. The article begins with a description of the software algorithms and techniques that allow visualization of and interaction with medical data. Example applications from research projects and commercially available products are listed, including educational tools; diagnostic aids; virtual endoscopy; planning aids; guidance aids; skills training; computer augmented reality and use of high performance computing. The final section of the paper summarizes the current issues and looks ahead to future developments. ER - TY - JFULL T1 - The hypothalamus, hormones, and hunger: alterations in human obesity and illness. A1 - Goldstone, AP J1 - Prog Brain Res Y1 - 2006/// VL - 153 SN - 0079-6123 SP - 57 EP - 73 N2 - Obesity is a major global epidemic, with over 300 million obese people worldwide, and nearly 1 billion overweight adults. Being overweight carries significant health risks, reduced quality of life, and impaired socioeconomic success, with profound consequences for health expenditure. The most successful treatment for obesity is gastric bypass surgery, which acts in part by reducing appetite through alterations in gut hormones. Circulating gut hormones, secreted or suppressed after eating food, act in the brain, particularly the hypothalamus, to alter hunger and fullness. Stomach-derived ghrelin increases food intake even in those with anorexia from chronic illness, while pancreatic polypeptide (PP), intestinal peptide YY 3-36 (PYY), oxyntomodulin, and other hormones reduce food intake and appetite. While obese subjects have appropriate reductions in orexigenic ghrelin, other gut-hormone disturbances may contribute to obesity such as reduced anorexigenic PYY and PP. Prader-Willi syndrome (PWS) arises from the loss of paternally inherited genes on chromosome 15q11-13, leading to life-threatening insatiable hunger and obesity from early childhood, through developmental brain, particularly hypothalamic defects. The study of genetically homogenous causes of abnormal-feeding behavior helps our understanding of appetite regulation. PWS subjects have inappropriately elevated plasma ghrelin for their obesity, at least partly explained by preserved insulin sensitivity. It remains unproven if their hyperghrelinemia or other gut-hormone abnormalities contribute to the hyperphagia in PWS, in addition to brain defects. Postmortem human hypothalamic studies and generation of animal models of PWS can also provide insight into the pathophysiology of abnormal-feeding behavior. Changes in orexigenic NPY and AGRP hypothalamic neurons, or anorexigenic oxytocin neurons have been found in illness and PWS. Functional neuroimaging studies, using PET and fMRI, will also allow us to tease apart the hormonal and brain pathways responsible for controlling human appetite, and their defects in obesity. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16876568&query_hl=1 ER - TY - JFULL T1 - Smooth vasculature reconstruction with circular and elliptic cross sections. A1 - Krissian, K A1 - Wu, X A1 - Luboz, V J1 - Stud Health Technol Inform Y1 - 2006/// VL - 119 SN - 0926-9630 SP - 273 EP - 278 N2 - This paper presents a method to segment and reconstruct vascular structure from patient volumetric scan. First, a semi-automatic segmentation phase leads to the vessels centerlines and the estimated circular or elliptic cross section description. Then, the skeleton data are used by the reconstruction phase to generate the three dimensional vascular surface. This structured surface is able to handle interactive visualization, real-time and robust physics-based modeling. The accuracy and consistency of our technique are evaluated on a vascular phantom as well as two clinical data sets. Experiments show that the proposed technique reaches a good balance in terms of mesh smoothness, compactness, and accuracy, where elliptic cross section estimation induces lower error. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16404060&query_hl=1 ER - TY - JFULL T1 - In vivo imaging of microglial activation with [11C](R)-PK11195 PET in progressive supranuclear palsy. A1 - Gerhard, A A1 - Trender-Gerhard, I A1 - Turkheimer, F A1 - Quinn, NP A1 - Bhatia, KP A1 - Brooks, DJ J1 - Mov Disord Y1 - 2006/01// VL - 21 SN - 0885-3185 SP - 89 EP - 93 N2 - Progressive supranuclear palsy (PSP) is a neurodegenerative disease presenting with voluntary gaze difficulties, early falls, and Parkinsonism. Neuronal loss, associated with intracellular neurofibrillary tangles and activated microglia, is found targeting the basal ganglia, brainstem nuclei, and frontal cortex. [11C](R)-PK11195 PET is a marker of peripheral benzodiazepine binding sites (PBBS) expressed by activated microglia. We have used [11C](R)-PK11195 PET to demonstrate in vivo the degree and distribution of the glial response to the degenerative process in four patients with PSP. Compared to normal age-matched controls, the PSP patient group showed significantly increased mean [11C](R)-PK11195 binding in the basal ganglia, midbrain, the frontal lobe, and the cerebellum. Two of the patients were rescanned after 6 to 10 months and during that time the level of microglial activation remained stable. [11C](R)-PK11195 PET reveals a pattern of increased microglial activation in PSP patients involving cortical and subcortical regions that corresponds well with the known distribution of neuropathological changes. [11C](R)-PK11195 PET, therefore, may help in characterizing in vivo the underlying disease activity in PSP. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16108021&query_hl=1 ER - TY - JFULL T1 - Quantification of growth and motion using non-rigid registration A1 - Rueckert, D A1 - Chandrashekara, R A1 - Ajabar, P A1 - Bhatia, KK A1 - Boardman, JP A1 - Srinivasan, L A1 - Rutherford, MA A1 - Dyet, LE A1 - Edwards, AD A1 - Hajnal, JV A1 - Mohiaddin, R J1 - LECT NOTES COMPUT SC Y1 - 2006/// VL - 4241 SN - 0302-9743 SP - 49 EP - 60 N2 - Three-dimensional (3D) and four-dimensional (4D) imaging of dynamic structures is a rapidly developing area of research in medical imaging. Non-rigid registration plays an important role for the analysis of these datasets. In this paper we will show some of the work of our group using non-rigid registration techniques for the detection of temporal changes such as growth in brain MR images. We will also show how non-rigid registration can be used to analyze the motion of the heart from cardiac MR images. ER - TY - JFULL T1 - Self-calibrating 3D-ultrasound-based bone registration for minimally invasive orthopedic surgery A1 - Barratt DC A1 - Penney GP A1 - Chan CSK A1 - Slomczykowski M A1 - Carter TJ A1 - Edwards PJ A1 - Hawkes DJ J1 - IEEE Trans Med Imaging Y1 - 2006/// IS - 3 VL - 25 SN - 0278-0062 SP - 312 EP - 323 ER - TY - JFULL T1 - Designing for e-Health: recurring scenarios in developing grid-based medical imaging systems. A1 - Geddes, J A1 - Mackay, C A1 - Lloyd, S A1 - Simpson, A A1 - Power, D A1 - Russell, D A1 - Jirotka, M A1 - Katzarova, M A1 - Rossor, M A1 - Fox, N A1 - Fletcher, J A1 - Hill, D A1 - McLeish, K A1 - Chen, Y A1 - Hajnal, JV A1 - Lawrie, S A1 - Job, D A1 - McIntosh, A A1 - Wardlaw, J A1 - Sandercock, P A1 - Palmer, J A1 - Perry, D A1 - Procter, R A1 - Ure, J A1 - Hartswood, M A1 - Slack, R A1 - Voss, A A1 - Ho, K A1 - Bath, P A1 - Clarke, W A1 - Watson, G J1 - Stud Health Technol Inform Y1 - 2006/// VL - 120 SN - 0926-9630 SP - 336 EP - 347 N2 - The paper draws on a number of Grid projects, particularly on the experience of NeuroGrid, a UK project in the Neurosciences tasked with developing a Grid-based collaborative research environment to support the sharing of digital images and patient data across multiple distributed sites. It outlines recurrent socio-technical issues, highlighting the challenges of scaling up technological networks in advance of the regulatory networks which normally regulate their use in practice. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16823151&query_hl=1 ER - TY - JFULL T1 - Multiclassifier fusion in human brain MR segmentation: modelling convergence. A1 - Heckemann, RA A1 - Hajnal, JV A1 - Aljabar, P A1 - Rueckert, D A1 - Hammers, A J1 - Med Image Comput Comput Assist Interv Int Conf Med Image Comput Comput Assist Interv Y1 - 2006/// VL - 9 SP - 815 EP - 822 N2 - Segmentations of MR images of the human brain can be generated by propagating an existing atlas label volume to the target image. By fusing multiple propagated label volumes, the segmentation can be improved. We developed a model that predicts the improvement of labelling accuracy and precision based on the number of segmentations used as input. Using a cross-validation study on brain image data as well as numerical simulations, we verified the model. Fit parameters of this model are potential indicators of the quality of a given label propagation method or the consistency of the input segmentations used. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17354848&query_hl=1 ER - TY - JFULL T1 - Imaging activated microglia in presymptomatic Huntington's disease gene carriers: An 11C-PK11195 PET study A1 - Tai, YF A1 - Pavese, N A1 - Gerhard, A A1 - Tabrizi, SJ A1 - Barker, RA A1 - Brooks, DJ A1 - Piccini, P J1 - J NEUROL NEUROSUR PS Y1 - 2006/01// VL - 77 SN - 0022-3050 SP - 138 EP - 138 ER - TY - JFULL T1 - Diffeomorphic registration using B-splines. A1 - Rueckert, D A1 - Aljabar, P A1 - Heckemann, RA A1 - Hajnal, JV A1 - Hammers, A J1 - Med Image Comput Comput Assist Interv Int Conf Med Image Comput Comput Assist Interv Y1 - 2006/// VL - 9 SP - 702 EP - 709 N2 - In this paper we propose a diffeomorphic non-rigid registration algorithm based on free-form deformations (FFDs) which are modelled by B-splines. In contrast to existing non-rigid registration methods based on FFDs the proposed diffeomorphic non-rigid registration algorithm based on free-form deformations (FFDs) which are modelled by B-splines. To construct a diffeomorphic transformation we compose a sequence of free-form deformations while ensuring that individual FFDs are one-to-one transformations. We have evaluated the algorithm on 20 normal brain MR images which have been manually segmented into 67 anatomical structures. Using the agreement between manual segmentation and segmentation propagation as a measure of registration quality we have compared the algorithm to an existing FFD registration algorithm and a modified FFD registration algorithm which penalises non-diffeomorphic transformations. The results show that the proposed algorithm generates diffeomorphic transformations while providing similar levels of performance as the existing FFD registration algorithm in terms of registration accuracy. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17354834&query_hl=1 ER - TY - JFULL T1 - Non-linear elastic properties of the lingual and facial tissues assessed by indentation technique. Application to the biomechanics of speech production. A1 - Gerard, JM A1 - Ohayon, J A1 - Luboz, V A1 - Perrier, P A1 - Payan, Y J1 - Med Eng Phys Y1 - 2005/12// VL - 27 SN - 1350-4533 SP - 884 EP - 892 N2 - This paper aims at characterizing the mechanical behavior of two human anatomical structures, namely the tongue and the cheek. For this, an indentation experiment was provided, by measuring the mechanical response of tongue and cheek tissues removed from the fresh cadaver of a 74 year old woman. Non-linear relationships were observed between the force applied to the tissues and the corresponding displacements. To infer the mechanical constitutive laws from these measurements, a finite element (FE) analysis was provided. This analysis aimed at simulating the indentation experiment. An optimization process was used to determine the FE constitutive laws that provided the non-linear force/displacements observed during the indentation experiments. The tongue constitutive law was used for simulations provided by a 3D FE biomechanical model of the human tongue. This dynamical model was designed to study speech production. Given a set of tongue muscular commands, which levels correspond to the force classically measured during speech production, the FE model successfully simulated the main tongue movements observed during speech data. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16280251&query_hl=1 ER - TY - JFULL T1 - Delivery of oligodeoxynucleotides into human saphenous veins and the adjunct effect of ultrasound and microbubbles. A1 - Kodama, T A1 - Tan, PH A1 - Offiah, I A1 - Partridge, T A1 - Cook, T A1 - George, AJ A1 - Blomley, MJ J1 - Ultrasound Med Biol Y1 - 2005/12// VL - 31 SN - 0301-5629 SP - 1683 EP - 1691 N2 - Therapy with naked oligodeoxynucleotides (ODNs, molecular weight: 3000 to 7500) provides an elegant means of modulating gene expression without the problems associated with conventional gene therapy, but the relatively low transfer efficiency on intravascular administration is a limitation to clinical application. Ultrasound, which can be potentiated by microbubbles, shows promise as a method of delivering macromolecules such as plasmid DNA and other transgenes into cells. Since uptake of molecules into cells depends on their molecular weight, it might be expected that the delivery of ODNs, which are relatively small, will be facilitated by ultrasound and microbubbles. In the present study, we delivered ODNs into veins using ultrasound and microbubbles. First, we quantified the uptake of fluorescent-labeled ODNs into intact ex vivo human saphenous veins and isolated smooth muscle cells from the veins, evaluating the effect of ultrasound and microbubbles on uptake. Ultrasound potentiated the delivery of ODN in cells, except at high concentrations. When intact veins were studied, we achieved nuclear localization of fluorescent-labeled ODNs in cells. This increased with increasing concentration and incubation time and was not potentiated by ultrasound, even when microbubbles were used. We then applied a therapeutic ODN (antisense to intercellular adhesion molecule 1, ICAM-1) to vein samples and documented a functional inhibition of gene expression in a sequence-specific manner at the protein level with immunohistochemistry and western blot analysis. Again, no significant difference was seen with adjunct ultrasound. These observations suggest high diffusion of ODNs into human saphenous veins in this ex vivo model, indicating potential applications to inhibition of vascular bypass graft occlusion and other vasculopathies. Although microbubble-ultrasound was of value with cells in culture, it was not beneficial with intact veins. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16344130&query_hl=1 ER - TY - JFULL T1 - Valveless pump models that laid a false but fortuitous trail on the way towards the total cavopulmonary connection. A1 - Kilner, PJ J1 - Cardiol Young Y1 - 2005/12// VL - 15 Suppl 3 SN - 1047-9511 SP - 74 EP - 79 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16248930&query_hl=1 ER - TY - JFULL T1 - Understanding specificity and sensitivity of T-cell recognition. A1 - George, AJ A1 - Stark, J A1 - Chan, C J1 - Trends Immunol Y1 - 2005/12// VL - 26 SN - 1471-4906 SP - 653 EP - 659 N2 - The response of T cells to antigen shows an amazing degree of both sensitivity and specificity, with a cell responding to 1-10 peptide-MHC complexes and being sensitive to single amino acid substitutions. Kinetic proofreading or feedback pathways achieve specificity at the level of the receptor, whereas serial engagement of receptors by ligand molecules enhances sensitivity. Crosstalk between receptors, integration of signals and/or tuning of responses is important at the level of the cell. Induction of anergic or regulatory cells by suboptimal stimuli prevents cell activation by multiple encounters with weak ligands. Thus, for optimal sensitivity and specificity, it is necessary to have mechanisms that operate at the level of the receptor, the cell and finally, the population of responding cells. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16236548&query_hl=1 ER - TY - JFULL T1 - Factors affecting the clinical outcome after neural transplantation in Parkinson's disease. A1 - Piccini, P A1 - Pavese, N A1 - Hagell, P A1 - Reimer, J A1 - Björklund, A A1 - Oertel, WH A1 - Quinn, NP A1 - Brooks, DJ A1 - Lindvall, O J1 - Brain Y1 - 2005/12// VL - 128 SN - 1460-2156 SP - 2977 EP - 2986 N2 - Intrastriatal grafts of embryonic mesencephalic tissue can survive in the brains of patients with Parkinson's disease, but the degree of symptomatic relief is highly variable and some cases develop troublesome dyskinesias. Here we explored, using clinical assessment and 18F-dopa and 11C-raclopride PET, factors which may influence the functional outcome after transplantation. We observed increased 18F-dopa uptake in the grafted putamen, signifying continued survival of the transplanted dopaminergic neurons, in parallel with a progressive reduction of 18F-dopa uptake in non-grafted regions for the whole patient group. The patients with the best functional outcome after transplantation exhibited no dopaminergic denervation in areas outside the grafted areas either preoperatively or at 1 or 2 years post-operatively. In contrast, patients with no or modest clinical benefit showed reduction of 18F-dopa in ventral striatum prior to or following transplantation, which may have limited graft-induced improvement. We obtained no evidence that dyskinesias were caused by abnormal dopamine (DA) release from the grafts. As has been observed for intrinsic dopaminergic neurons, there was a significant correlation between 18F-dopa uptake and methamphetamine-induced change of 11C-raclopride binding (as a measure of DA release) in the putamen containing the graft. Furthermore, we observed no correlation between 11C-raclopride binding in anterior, posterior or entire putamen under basal conditions or after methamphetamine, and dyskinesia severity scores in the contralateral side of the body. Withdrawal of immunosuppression at 29 months after transplantation caused no reduction of 18F-dopa uptake or worsening of UPDRS motor score, indicating continued survival and function of the graft. However, patients showed increased dyskinesia scores, which might have been caused either by growth of the graft or worsening of a low-grade inflammation around the graft. These findings indicate that poor outcome after transplantation is associated with progressive dopaminergic denervation in areas outside the grafts, a process which may have started already before surgery. Also, that the development of dyskinesias after transplantation is not associated with excessive DA release from the grafts. Finally, our data provide evidence that long-term immunosuppression can be withdrawn without interfering with graft survival or the motor recovery induced by transplantation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16246865&query_hl=1 ER - TY - JFULL T1 - Fetal cardiac interventions. A1 - Gardiner, HM A1 - Kumar, S J1 - Clin Obstet Gynecol Y1 - 2005/12// VL - 48 SN - 0009-9201 SP - 956 EP - 963 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16286841&query_hl=1 ER - TY - JFULL T1 - Padé methods for reconstruction and feature extraction in magnetic resonance imaging. A1 - Callaghan, MF A1 - Larkman, DJ A1 - Hajnal, JV J1 - Magn Reson Med Y1 - 2005/12// VL - 54 SN - 0740-3194 SP - 1490 EP - 1502 N2 - Methods utilizing Padé approximants are investigated for implementation with magnetic resonance imaging data and are presented both for direct image reconstruction and for feature extraction. Padé approximants are a numerical tool that can be used to accelerate the convergence of a slowly converging sequence by estimating the fully converged sequence values from early data points. Padé approximants can be calculated directly from k-space data by solving a set of linear matrix equations to produce signal values for any desired location in the image domain. This gives an estimate of the fully converged signal intensity at each pixel location in the image, raising the possibility of reconstructing a better estimate of the object from a reduced data set. These methods have been tested on phantom and human data both for image reconstruction and for feature extraction. In image reconstruction, considerable convergence acceleration can be achieved, with steep intensity boundaries reproduced in keeping with higher resolution reconstructions and oscillatory truncation artifact characteristic of Fourier reconstruction removed. The convergence acceleration is variable and there is the possibility of fine detail suppression when insufficient data are included. The use of Padé methods as a tool for feature extraction has shown good agreement with extraction from high-resolution reference data. In this approach the edge information comes intrinsically from Padé reconstruction. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16254953&query_hl=1 ER - TY - JFULL T1 - The impact of multiple T cell-APC encounters and the role of anergy A1 - Chan, C A1 - Stark, J A1 - George, AJT J1 - J COMPUT APPL MATH Y1 - 2005/12/01/ VL - 184 SN - 0377-0427 SP - 101 EP - 120 N2 - The activation of a T cell is a stochastic process, and depends on the integrated strength of signals I and 2 resulting from its encounter with an antigen presenting cell. The net outcome of thymic selection and peripheral circulation over many such encounters in the presence of mechanisms for both central and peripheral tolerance is difficult to deduce by intuition alone. We therefore introduce a simple mathematical model that allows us to explore the roles and interaction of different thresholds, costimulation and anergy, as well as make predictions about expected immune system behaviour. We show that stochastic activation in the context of repeated encounters results in lowering the apparent activation threshold for T cells. This effect may contribute significantly to the efficiency of negative selection, although a low avidity subset of auto-reactive thymocytes can still be exported. A simple peripheral mechanism for peripheral tolerance is shown to be highly effective at dealing with this low avidity subset. Finally, the trade-offs between sensitivity and specificity are examined. (c) 2005 Elsevier B.V. All rights reserved. ER - TY - JFULL T1 - Chorea associated with thyroxine replacement therapy. A1 - Isaacs, JD A1 - Rakshi, J A1 - Baker, R A1 - Brooks, DJ A1 - Warrens, AN J1 - Mov Disord Y1 - 2005/12// VL - 20 SN - 0885-3185 SP - 1656 EP - 1657 N2 - Chorea is an uncommonly reported manifestation of hyperthyroidism. We report the first description of generalized chorea due to iatrogenic thyrotoxicosis and propose that the movement disorder is due to a direct effect of thyroxine on the basal ganglia rather than being an autoimmune phenomenon. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16078207&query_hl=1 ER - TY - JFULL T1 - The evolving role of gene-based treatment in surgery. A1 - Tan, PH A1 - Chan, CL A1 - Chan, C A1 - George, AJ J1 - Br J Surg Y1 - 2005/12// VL - 92 SN - 0007-1323 SP - 1466 EP - 1480 N2 - BACKGROUND: The completion of the sequencing of the human genome in 2003 marked the dawn of a new era of human biology and medicine. Although these remarkable scientific advances improve the understanding of human biology, the question remains how this rapidly expanding knowledge of functional genomics affects the role of surgeons. This article reviews the potential therapeutic application of gene therapy for various surgical conditions. METHODS: The core of this review was derived from a Medline database literature search. RESULTS AND CONCLUSION: The currently available vectors in the field of gene therapy and their limitations for clinical applications were analysed. The achievements of gene therapy in clinical trials and the future ramifications for surgery were also explored. Whether gene therapy takes a major role in surgical practice will depend greatly on the success of future vector development. Advances in viral vector technology to reduce the inflammatory effect, and improvements in the efficiency of gene delivery using non-viral vector technology, would allow this form of therapy to become more clinically applicable. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16273530&query_hl=1 ER - TY - JFULL T1 - Inter-study reproducibility of 3D volume selective fast spin echo sequence for quantifying carotid artery wall volume in asymptomatic subjects. A1 - Varghese, A A1 - Crowe, LA A1 - Mohiaddin, RH A1 - Gatehouse, PD A1 - Yang, GZ A1 - Firmin, DN A1 - Pennell, DJ J1 - Atherosclerosis Y1 - 2005/12// VL - 183 SN - 0021-9150 SP - 361 EP - 366 N2 - PURPOSE: To determine, in asymptomatic subjects, the inter-study reproducibility of a three-dimensional (3D) volume selective fast spin echo (FSE) cardiovascular magnetic resonance sequence for the assessment of carotid artery wall volume as a measure of atheroma burden. METHODS: Inter-study reproducibility was evaluated in 16 asymptomatic volunteers (10 male, 6 female). Both carotid arteries were scanned twice with a median inter-scan time of 5 days. The images were acquired in cross-section, and the total carotid arterial wall volume (TWV) was calculated by subtraction of the total carotid lumen volume from the total outer carotid vessel volume. RESULTS: The mean carotid T1-weighted TWV for the first and second scans was 828 and 821 mm(3), respectively (mean difference 7 mm(3), p=0.45). The standard deviation (S.D.) of the differences between the measurements was 38 mm(3) yielding an inter-study coefficient of variation of 4.6%. The time for each study was approximately 30 min. For the longitudinal evaluation of carotid atheroma burden with pharmacological intervention versus placebo, 32 subjects would enable a difference of 38 mm(3) to be detected with a significance level of 5% with 80% power. CONCLUSION: Volumetric analysis with carotid CMR in asymptomatic subjects using a 3D volume-selective FSE is time-efficient with good inter-study reproducibility, and is well suited for longitudinal studies of carotid atheroma with reasonable sample sizes. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16285999&query_hl=1 ER - TY - JFULL T1 - Progression of fetal heart disease and rationale for fetal intracardiac interventions. A1 - Gardiner, HM J1 - Semin Fetal Neonatal Med Y1 - 2005/12// VL - 10 SN - 1744-165X SP - 578 EP - 585 N2 - The outcome of cardiac disease diagnosed before birth is paradoxically worse than that diagnosed postnatally. In part, this is because fetal screening detects cases that are already showing failure of cardiac growth which are usually progressive with secondary damage to the myocardium, lungs and brain. Fetal valvuloplasty has been proposed for cases of critical aortic and pulmonary stenosis or atresia, and atrial septostomy for a restrictive oval foramen associated with aortic stenosis, hypoplastic left heart syndrome and transposition of the great arteries. The rationale for fetal therapy is to restore forward flow and reduce intraventricular pressure, thus improving coronary perfusion and minimizing ischaemic damage. Successful valvuloplasty has reduced systemic venous pressures and reversed fetal hydrops, thus prolonging pregnancy. It has resulted in improved ventricular growth in some cases and spontaneous opening of a closed oval foramen with normalization of pulmonary venous waveforms. These signs suggest better fetal cardiopulmonary development and improved surgical outcomes. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16213202&query_hl=1 ER - TY - JFULL T1 - Improved myocardial T2*in transfusion dependent anemias receiving ICL670 (Deferasirox) A1 - Porter, JB A1 - Tanner, MA A1 - Pennell, DJ A1 - Eleftheriou, P J1 - BLOOD Y1 - 2005/11/16/ VL - 106 SN - 0006-4971 SP - 1003A EP - 1003A ER - TY - JFULL T1 - The effect of combined chelation therapy in the treatment of severe myocardial iron loading in beta Thalassaemia major. A1 - Tanner, MA A1 - Galanello, R A1 - Dessi, C A1 - Westwood, MA A1 - Pennell, DJ J1 - BLOOD Y1 - 2005/11/16/ VL - 106 SN - 0006-4971 SP - 39B EP - 39B ER - TY - JFULL T1 - Calibration of myocardial T2*values in post-mortem hearts A1 - Pennell, DJ A1 - Anderson, LJ A1 - Paul, K A1 - Forni, GL A1 - Ellis, G A1 - Walker, JM A1 - Porter, JB J1 - BLOOD Y1 - 2005/11/16/ VL - 106 SN - 0006-4971 SP - 40B EP - 40B 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 thalassaemia major using cardiovascular magnetic resonance. A1 - Tanner, MA A1 - Galanello, R A1 - Dessi, C A1 - Westwood, MA A1 - Smith, GC A1 - Khan, M A1 - Nair, SV A1 - Walker, JM A1 - Pennell, DJ J1 - BLOOD Y1 - 2005/11/16/ VL - 106 SN - 0006-4971 SP - 1017A EP - 1017A ER - TY - JFULL T1 - Validation of T2*technique in ex-vivo myocardial tissue. A1 - Kirk, P A1 - Firmin, DN A1 - Sampson, B A1 - Porter, JB A1 - Walker, MJ A1 - Pennell, DJ J1 - BLOOD Y1 - 2005/11/16/ VL - 106 SN - 0006-4971 SP - 7B EP - 7B ER - TY - JFULL T1 - Myocardial T2*is not affected by the structural effects of myocardial fibrosis, ageing or impaired left ventricular function. A1 - Kirk, P A1 - Pennell, DJ J1 - BLOOD Y1 - 2005/11/16/ VL - 106 SN - 0006-4971 SP - 478A EP - 478A 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 - Prescott, E A1 - Porter, JB A1 - Wonke, B A1 - Walker, MJ A1 - Pennell, DJ J1 - BLOOD Y1 - 2005/11/16/ VL - 106 SN - 0006-4971 SP - 760A EP - 760A ER - TY - JFULL T1 - Myocardial T2*in patients with cardiac failure secondary to iron overload. A1 - Tanner, MA A1 - Porter, JB A1 - Westwood, MA A1 - Nair, SV A1 - Anderson, LJ A1 - Walker, JM A1 - Pennell, DJ J1 - BLOOD Y1 - 2005/11/16/ VL - 106 SN - 0006-4971 SP - 40B EP - 40B ER - TY - JFULL T1 - Matrix description of general motion correction applied to multishot images. A1 - Batchelor, PG A1 - Atkinson, D A1 - Irarrazaval, P A1 - Hill, DL A1 - Hajnal, J A1 - Larkman, D J1 - Magn Reson Med Y1 - 2005/11// VL - 54 SN - 0740-3194 SP - 1273 EP - 1280 N2 - Motion of an object degrades MR images, as the acquisition is time-dependent, and thus k-space is inconsistently sampled. This causes ghosts. Current motion correction methods make restrictive assumptions on the type of motions, for example, that it is a translation or rotation, and use special properties of k-space for these transformations. Such methods, however, cannot be generalized easily to nonrigid types of motions, and even rotations in multiple shots can be a problem. Here, a method is presented that can handle general nonrigid motion models. A general matrix equation gives the corrupted image from the ideal object. Thus, inversion of this system allows us to get the ideal image from the corrupted one. This inversion is possible by efficient methods mixing Fourier transforms with the conjugate gradient method. A faster but empirical inversion is discussed as well as methods to determine the motion. Simulated three-dimensional affine data and two-dimensional pulsation data and in vivo nonrigid data are used for demonstration. All examples are multishot images where the object moves between shots. The results indicate that it is now possible to correct for nonrigid types of motion that are representative of many types of patient motion, although computation times remain an issue. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16155887&query_hl=1 ER - TY - JFULL T1 - Creation of tolerogenic human dendritic cells via intracellular CTLA4: a novel strategy with potential in clinical immunosuppression. A1 - Tan, PH A1 - Yates, JB A1 - Xue, SA A1 - Chan, C A1 - Jordan, WJ A1 - Harper, JE A1 - Watson, MP A1 - Dong, R A1 - Ritter, MA A1 - Lechler, RI A1 - Lombardi, G A1 - George, AJ J1 - Blood Y1 - 2005/11/01/ VL - 106 SN - 0006-4971 SP - 2936 EP - 2943 N2 - Activation of T lymphocytes requires the recognition of peptide-major histocompatibility complexes (MHCs) and costimulatory signals provided by antigen-presenting cells (APCs). It has been shown that T-cell activation without costimulation can lead to anergy. In this study, we developed a novel strategy to inhibit expression of B7 molecules (CD80/86) by transfecting APCs with a gene construct encoding a modified cytotoxic T lymphocyte antigen 4 (CTLA4) molecule (CTLA4-KDEL) that is targeted to the endoplasmic reticulum (ER). APCs expressing this construct failed to express CD80/86 on their surface, were unable to stimulate allogeneic and peptide-specific T-cell responses, and induced antigen-specific anergy of the responding T cells. Cells expressing CTLA4-KDEL do not up-regulate the indoleamine 2, 3-dioxygenase enzyme, unlike cells treated with soluble CTLA4-immunoglobin (Ig). This gene-based strategy to knock out surface receptors is an attractive alternative to using immature dendritic cells for preventing transplant rejection and treating of autoimmune diseases. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15994283&query_hl=1 ER - TY - JFULL T1 - Improved accuracy of low-power contrast echocardiography for the assessment of left ventricular remodeling compared with unenhanced harmonic echocardiography after acute myocardial infarction: comparison with cardiovascular magnetic resonance imaging. A1 - Lim, TK A1 - Burden, L A1 - Janardhanan, R A1 - Ping, C A1 - Moon, J A1 - Pennell, D A1 - Senior, R J1 - J Am Soc Echocardiogr Y1 - 2005/11// VL - 18 SN - 0894-7317 SP - 1203 EP - 1207 N2 - BACKGROUND: Assessment of left ventricular (LV) remodeling after acute myocardial infarction (AMI) has both therapeutic and prognostic implications. Low-power contrast echocardiography (CE) has the advantage of simultaneously assessing myocardial perfusion and LV remodeling. OBJECTIVE: This study aimed to evaluate the accuracy of low-power CE to assess LV remodeling after AMI compared with unenhanced harmonic echocardiography (HE). METHODS: A total of 36 consecutive patients underwent HE, CE (SonoVue), and cardiovascular magnetic resonance (CMR) imaging 7 to 10 days after AMI. Left ventricular ejection fraction (LVEF), end-systolic volume (LVESV), and end-diastolic volume (LVEDV) were assessed. RESULTS: Absolute differences for LVESV and LVEDV between CMR and CE were significantly smaller than those between CMR and HE. CE estimate of LVEF more accurately classified patients into LVEF < 35%, 35% to 45%, and > 45% (agreement, 83%; kappa = 0.66 with CMR) compared with HE (agreement, 69%; kappa = 0.33 with CMR). CONCLUSIONS: Low-power CE is more accurate than HE for estimating LV remodeling after AMI. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16275530&query_hl=1 ER - TY - JFULL T1 - Computer assisted planning and orbital surgery: patient-related prediction of osteotomy size in proptosis reduction. A1 - Luboz, V A1 - Ambard, D A1 - Swider, P A1 - Boutault, F A1 - Payan, Y J1 - Clin Biomech (Bristol, Avon) Y1 - 2005/11// VL - 20 SN - 0268-0033 SP - 900 EP - 905 N2 - BACKGROUND: Proptosis is characterized by a protrusion of the eyeball due to an increase of the orbital tissue volume. To recover a normal eyeball positioning, the most frequent surgical technique consists in the osteotomy of orbital walls combined with the manual loading on the eyeball. Only a rough clinical rule is currently available for the surgeons but it is useless for this technique. The first biomechanical model dealing with proptosis reduction, validated in one patient, has been previously proposed by the authors. METHODS: This paper proposes a rule improving the pre-operative planning of the osteotomy size in proptosis reduction. Patient-related poroelastic finite element models combined with sensitivity studies were used to propose two clinical rules to improve the pre-operative planning of proptosis reduction. This poroelastic model was run on 12 patients. Sensitivity studies permitted to establish relationships between the osteotomy size, the patient-related orbital volume, the decompressed tissue volume and the eyeball backward displacement. FINDINGS: The eyeball displacement and the osteotomy size were non-linearly related: an exponential rule has been proposed. The patient-related orbital volume showed a significant influence: a bi-quadratic analytical equation liking the osteotomy size, the orbital volume and the targeted eyeball protrusion has been established. INTERPRETATION: Two process rules derived from patient-related biomechanical FE models have been proposed for the proptosis reduction planning. The implementation of the process rules into a clinical setting is easy since only a sagittal radiography is required. The osteotomy size can be monitored using optical guided instruments. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16115709&query_hl=1 ER - TY - JFULL T1 - Randomized comparison of stentless versus stented valves for aortic stenosis: effects on left ventricular mass. A1 - Perez de Arenaza, D A1 - Lees, B A1 - Flather, M A1 - Nugara, F A1 - Husebye, T A1 - Jasinski, M A1 - Cisowski, M A1 - Khan, M A1 - Henein, M A1 - Gaer, J A1 - Guvendik, L A1 - Bochenek, A A1 - Wos, S A1 - Lie, M A1 - Van Nooten, G A1 - Pennell, D A1 - Pepper, J A1 - ASSERT (Aortic Stentless versus Stented valve assessed by Echocardiography Randomized Trial) Investigators J1 - Circulation Y1 - 2005/10/25/ VL - 112 SN - 1524-4539 SP - 2696 EP - 2702 N2 - BACKGROUND: Aortic valve replacement (AVR) is the established treatment for severe aortic stenosis. In response to the long-term results of aortic homografts, stentless porcine valves were introduced as an alternative low-resistance valve. We conducted a randomized trial comparing a stentless with a stented porcine valve in adults with severe aortic stenosis. METHODS AND RESULTS: The primary outcome was change in left ventricular mass index (LVMI) measured by transthoracic echocardiography and, in a subset, by cardiovascular MR. Measurements were taken before valve replacement and at 6 and 12 months. Patients undergoing AVR with an aortic annulus < or =25 mm in diameter were randomly allocated to a stentless (n=93) or a stented supra-annular (n=97) valve. There were no significant differences in mean LVMI between the stentless versus stented groups at baseline (176+/-62 and 182+/-63 g/m2, respectively) or at 6 months (142+/-49 and 131+/-45 g/m2, respectively), although within-group changes from baseline to 6 months were highly significant. Changes in LVMI measured by cardiovascular MR (n=38) were consistent with the echo findings. There was a greater reduction in peak aortic velocity (P<0.001) and a greater increase in indexed effective orifice area (P<0.001) in the stentless group than in the stented group. There were no differences in clinical outcomes between the 2 valve groups. CONCLUSIONS: Despite significant differences in indexed effective orifice area and peak flow velocity in favor of the stentless valve, there were similar reductions in left ventricular mass at 6 months with both stented and stentless valves, which persisted at 12 months. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16230487&query_hl=1 ER - TY - JFULL T1 - Percutaneous fetal vaIvuloplasty: Four years' experience A1 - Gardiner, HM A1 - Franklin, RC A1 - Daubeney, PE A1 - Rigby, ML A1 - Kumar, S J1 - CIRCULATION Y1 - 2005/10/25/ VL - 112 SN - 0009-7322 SP - U711 EP - U712 ER - TY - JFULL T1 - Cholangiocarcinoma. A1 - Khan, SA A1 - Thomas, HC A1 - Davidson, BR A1 - Taylor-Robinson, SD J1 - Lancet Y1 - 2005/10/08/ VL - 366 SN - 1474-547X SP - 1303 EP - 1314 N2 - Cholangiocarcinoma is a devastating malignancy that presents late, is notoriously difficult to diagnose, and is associated with a high mortality. The incidence of intrahepatic cholangiocarcinoma is increasing worldwide. The cause for this rise is unclear, although it could be related to an interplay between predisposing genetic factors and environmental triggers. MRI and CT with endoscopic ultrasound and PET provide useful diagnostic information in certain patients. Surgical resection is the only chance for cure, with results depending on careful technique and patient selection. Data suggest that liver transplantation could offer long-term survival in selected patients when combined with neoadjuvant chemoradiotherapy. Chemotherapy and radiotherapy have been ineffective for patients with inoperable tumours. For most of these patients biliary drainage is the mainstay of palliation. However, controversy exists over the type and positioning of biliary stents. Photodynamic treatment is a new palliative technique that might improve quality of life. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16214602&query_hl=1 ER - TY - JFULL T1 - In vivo imaging of activated microglia by 11C-(R)-PK11195 PET. A biomarker of neuroinflammation in Huntington's disease? A1 - Pavese, N A1 - Gerhard, A A1 - Tai, YF A1 - Ho, AK A1 - Turkheimer, F A1 - Barker, RA A1 - Brooks, DJ A1 - Piccini, P J1 - J NEUROL NEUROSUR PS Y1 - 2005/10// VL - 76 SN - 0022-3050 ER - TY - JFULL T1 - The internal capsule in neonatal imaging. A1 - Cowan, FM A1 - de Vries, LS J1 - Semin Fetal Neonatal Med Y1 - 2005/10// VL - 10 SN - 1744-165X SP - 461 EP - 474 N2 - The internal capsule is highly visible on conventional magnetic resonance imaging (MRI). It is myelinating rapidly at term, and the time course of its maturation is well known. It carries the major motor and sensory pathways to and from the cortex and the spinal cord. Additionally, fibres from the thalamus pass through it connecting to most regions of the cortex. It is therefore of vital importance, and damage to it has severe consequences. Its abnormal appearance on conventional MRI is a good predictor of an abnormal motor outcome in different clinical situations encountered in perinatal medicine. Its normal appearance on conventional MR images at term age is usually associated with a relatively normal motor outcome. More recently, diffusion-weighted and diffusion tensor imaging have allowed a much more sophisticated assessment of its maturation and connectivity; this has already led to a better understanding of how its development is affected by preterm birth and by hypoxic-ischaemic brain injury. Future studies will assess the relevance of these findings not only for motor outcome but also for cognitive, visual and sensory abilities. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16002354&query_hl=1 ER - TY - JFULL T1 - Recent advances in imaging the fetus and newborn. A1 - Cowan, FM A1 - Rutherford, M J1 - Semin Fetal Neonatal Med Y1 - 2005/10// VL - 10 SN - 1744-165X SP - 401 EP - 402 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15996540&query_hl=1 ER - TY - JFULL T1 - Intercentre reproducibility of magnetic resonance T2* measurements of myocardial iron in thalassaemia. A1 - Westwood, MA A1 - Firmin, DN A1 - Gildo, M A1 - Renzo, G A1 - Stathis, G A1 - Markissia, K A1 - Vasili, B A1 - Pennell, DJ J1 - Int J Cardiovasc Imaging Y1 - 2005/10// VL - 21 SN - 1569-5794 SP - 531 EP - 538 N2 - In transfusion-dependent thalassemia major, iron-induced cardiomyopathy is the predominant cause of morbidity and mortality. Assessment of myocardial iron loading using MRI gradient echo T2* measurements have been described, but has only been performed at one centre in London. We assessed the transferability of this method by comparing the results from three different MR scanners in three different countries. Ten patients with thalassemia major underwent myocardial T2* assessment using a Siemens Sonata Scanner in London. Patients were also scanned with either a similar T2* sequence on a GE Systems CVI scanner in Athens, or a GE Systems signa echospeed scanner in Cagliari. Two scans were performed at the respective site in all patients to assess interstudy reproducibility at each site. The mean difference and coefficient of variability for the heart between scanners was 0.08 ms and 9.7% between London and Athens; and 0.30 ms and 1.6% between London and Cagliari. The interstudy mean difference and coefficient of variability for the heart in Athens was 0.6 ms and 3.5%, and 0.2 ms and 2.4% in Cagliari. In conclusion, the myocardial iron estimations were consistent between the three centres with scanners of differing manufacture, suggesting that this technique may have widespread application in the assessment of patients with iron overload conditions such as thalassaemia. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16175443&query_hl=1 ER - TY - JFULL T1 - A review of cognitive impairment and cerebral metabolite abnormalities in patients with hepatitis C infection. A1 - Forton, DM A1 - Allsop, JM A1 - Cox, IJ A1 - Hamilton, G A1 - Wesnes, K A1 - Thomas, HC A1 - Taylor-Robinson, SD J1 - AIDS Y1 - 2005/10// VL - 19 Suppl 3 SN - 0269-9370 SP - S53 EP - S63 N2 - Numerous studies have reported associations between chronic hepatitis C virus (HCV) infection and fatigue, depression and impairments in health-related quality of life, which are independent of the severity of liver disease. Although there are a large number of potential explanations for these symptoms, including a history of substance abuse and associated personality types, or the effect of the diagnosis of HCV infection itself, there has been recent interest in the possibility of a biological effect of HCV infection on cerebral function. There is emerging evidence of mild, but significant neurocognitive impairment in HCV infection, which cannot be wholly attributed to substance abuse, co-existent depression or hepatic encephalopathy. Impairments are predominantly in the domains of attention, concentration and information processing speed. Furthermore, in-vivo cerebral magnetic resonance spectroscopy studies in patients with hepatitis C and normal liver function have reported elevations in cerebral choline-containing compounds and reductions in N-acetyl aspartate, suggesting that a biological mechanism may underlie the cognitive findings. The recent detection of HCV genetic sequences in post-mortem brain tissue raises the intriguing possibility that HCV infection of the central nervous system may be related to the reported neuropsychological symptoms and cognitive impairment. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16251829&query_hl=1 ER - TY - JFULL T1 - Does heroin release dopamine? A positron emission tomography study A1 - Daglish, M A1 - Lingford-Hughes, AR A1 - Grasby, PG A1 - Brooks, DJ A1 - Nutt, DJ J1 - EUR NEUROPSYCHOPHARM Y1 - 2005/10// VL - 15 SN - 0924-977X SP - S341 EP - S341 ER - TY - JFULL T1 - Mild hypothermia and the distribution of cerebral lesions in neonates with hypoxic-ischemic encephalopathy. A1 - Rutherford, MA A1 - Azzopardi, D A1 - Whitelaw, A A1 - Cowan, F A1 - Renowden, S A1 - Edwards, AD A1 - Thoresen, M J1 - Pediatrics Y1 - 2005/10// VL - 116 SN - 1098-4275 SP - 1001 EP - 1006 N2 - Hypothermia induced by whole-body cooling (WBC) and selective head cooling (SHC) both reduce brain injury after hypoxia-ischemia in newborn animals, but it is not known how these treatments affect the incidence or pattern of brain injury in human newborns. To assess this, 14 term infants with hypoxic-ischemic encephalopathy (HIE) treated with SHC, 20 infants with HIE treated with WBC, and 52 noncooled infants with HIE of similar severity were studied with magnetic resonance imaging in the neonatal period. Infants fulfilling strict criteria for HIE were recruited into the study after assessment of an amplitude-integrated electroencephalography (aEEG). Cooling was commenced within 6 hours of birth and continued for 48 to 72 hours. Hypothermia was not associated with unexpected or unusual lesions, and the prevalence of intracranial hemorrhage was similar in all 3 groups. Both modes of hypothermia were associated with a decrease in basal ganglia and thalamic lesions, which are predictive of abnormal outcome. This decrease was significant in infants with a moderate aEEG finding but not in those with a severe aEEG finding. A decrease in the incidence of severe cortical lesions was seen in the infants treated with SHC. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16199715&query_hl=1 ER - TY - JFULL T1 - A comparison of MR cholangiopancreatography at 1.5 and 3.0 Tesla. A1 - O'Regan, DP A1 - Fitzgerald, J A1 - Allsop, J A1 - Gibson, D A1 - Larkman, DJ A1 - Cokkinos, D A1 - Hajnal, JV A1 - Schmitz, SA J1 - Br J Radiol Y1 - 2005/10// VL - 78 SN - 0007-1285 SP - 894 EP - 898 N2 - Clinical MR systems operating at 3.0 Tesla have the potential to significantly improve spatial resolution due to the boost in intrinsic signal to noise ratio. However, body imaging at these field strengths presents a number of technical challenges. We performed a prospective pilot study in which 10 patients underwent an MR cholangiopancreatography (MRCP) examination consecutively on 1.5 and 3.0 Tesla systems (both Philips Intera). An axial half Fourier segmented turbo spin echo (HASTE) sequence and a coronal thick-slab 2D turbo-spin echo (TSE) sequence were compared on both systems. A reader measured the signal intensity (SI) ratios of common bile duct (CBD): liver, and CBD: fat on HASTE images and CBD: liver on the TSE images. A second reader performed a qualitative analysis of the intrahepatic and extrahepatic biliary anatomy. Quantitative data was compared using the paired t-test and qualitative data with the paired Wilcoxon signed rank test with p < 0.05. The quantitative analysis of the HASTE sequences showed a slightly higher signal intensity ratio (CBD:liver) at 3.0 Tesla compared with 1.5 Tesla (8.1 vs 5.6, p = 0.002). No significant difference was found between the SI ratios of (CBD:fat) on HASTE images or (CBD:liver) on TSE images. The qualitative analysis showed superior image quality of 3.0 Tesla over 1.5 Tesla images on both HASTE (31 vs 25, p = 0.032), and TSE sequences (34 vs 28, p = 0.043). This pilot study shows that MRCP is feasible at 3.0 Tesla with some improvement in image quality and signal characteristics. Further development may be achieved with sequence optimization and improved coil design. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16177011&query_hl=1 ER - TY - JFULL T1 - Imaging brain opioid receptors in alcohol and heroin dependence A1 - Lingford-Hughes, AR A1 - Daglish, M A1 - Brooks, DJ A1 - Nutt, DJ J1 - EUR NEUROPSYCHOPHARM Y1 - 2005/10// VL - 15 SN - 0924-977X SP - S331 EP - S331 ER - TY - JFULL T1 - Microglial activation in presymptomatic Huntington's disease gene carriers: A C-11-PK11195 pet study A1 - Tai, YF A1 - Pavese, N A1 - Gerhard, A A1 - Tabrizi, SJ A1 - Barker, RA A1 - Brooks, DJ A1 - Piccini, P J1 - J NEUROL NEUROSUR PS Y1 - 2005/10// VL - 76 SN - 0022-3050 ER - TY - JFULL T1 - Universal DNA primers amplify bacterial DNA from human fetal membranes and link Fusobacterium nucleatum with prolonged preterm membrane rupture. A1 - Cahill, RJ A1 - Tan, S A1 - Dougan, G A1 - O'Gaora, P A1 - Pickard, D A1 - Kennea, N A1 - Sullivan, MH A1 - Feldman, RG A1 - Edwards, AD J1 - Mol Hum Reprod Y1 - 2005/10// VL - 11 SN - 1360-9947 SP - 761 EP - 766 N2 - A large number of bacterial species have been identified in fetal membranes after preterm labour (PTL) associated with intrauterine infection by microbiological culture. In this study, we have investigated a molecular and bioinformatic approach to organism identification which surmounts the need for specific and diverse microbiological culture conditions required by conventional methods. Samples of fetal membranes were taken from 37 preterm infants, and 6 normal term controls delivered by caesarean section, in which bacteria had been detected by in situ hybridization of 16S ribosomal RNA using a generic probe. Degenerate primers were designed to amplify bacterial 16S ribosomal DNA by PCR and used to amplify bacterial DNA from human fetal membranes. Amplicons were cloned, sequenced and bacteria were identified bioinformatically by comparison of sequences with known bacterial DNA genomes. In situ hybridization using an organism specific probe was then used to confirm the presence of the commonest identified organism in tissue samples. Bacterial DNA amplified from 15/43 samples, all from preterm deliveries, and the bioinformatic approach identified organisms in all cases. Multiple bacteria were identified including Mycoplasma hominis, Pasturella multocida, Pseudomonas PH1, Escherichia coli and Prevotella bivia. The commonest organism Fusobacterium nucleatum was found in 9/15 (60%) of samples. Ten of the 12 samples obtained after prolonged membrane rupture were positive for bacterial DNA, and 7 of these (70%) contained DNA from F. nucleatum. Bacteria from fetal membranes may be identified by molecular and bioinformatic methods. Further work is warranted to investigate the apparent linkage between F. nucleatum, fetal membrane rupture and preterm delivery. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16254004&query_hl=1 ER - TY - JFULL T1 - Influence of ionic strength on the time course of force development and phosphate release by dogfish muscle fibres. A1 - West, TG A1 - Ferenczi, MA A1 - Woledge, RC A1 - Curtin, NA J1 - J Physiol Y1 - 2005/09/15/ VL - 567 SN - 0022-3751 SP - 989 EP - 1000 N2 - We measured the effects of ionic strength (IS), 200 (standard) and 400 mmol l(-1) (high), on force and ATP hydrolysis during isometric contractions of permeabilized white fibres from dogfish myotomal muscle at their physiological temperature, 12 degrees C. One goal was to test the validity of our kinetic scheme that accounts for energy release, work production and ATP hydrolysis. Fibres were activated by flash photolysis of the P(3)-1-(2 nitrophenyl) ethyl ester of ATP (NPE-caged ATP), and time-resolved phosphate (P(i)) release was detected with the fluorescent protein MDCC-PBP, N-(2[1-maleimidyl]ethyl)-7-diethylamino-coumarin-3-carboxamide phosphate binding protein. High IS slowed the transition from rest to contraction, but as the fibres approached the isometric force plateau they showed little IS sensitivity. By 0.5 s of contraction, the force and the rate of P(i) release at standard and high IS values were not significantly different. A five-step reaction mechanism was used to account for the observed time courses of force and P(i) release in all conditions explored here. Only the rate constants for reactions of ATP, ADP and P(i) with the contractile proteins varied with IS, thus suggesting that the actin-myosin interactions are largely non-ionic. Our reaction scheme also fits previous results for intact fibres. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16037082&query_hl=1 ER - TY - JFULL T1 - Cdc42 and Par6-PKCzeta regulate the spatially localized association of Dlg1 and APC to control cell polarization. A1 - Etienne-Manneville, S A1 - Manneville, JB A1 - Nicholls, S A1 - Ferenczi, MA A1 - Hall, A J1 - J Cell Biol Y1 - 2005/09/12/ VL - 170 SN - 0021-9525 SP - 895 EP - 901 N2 - Cell polarization is essential in a wide range of biological processes such as morphogenesis, asymmetric division, and directed migration. In this study, we show that two tumor suppressor proteins, adenomatous polyposis coli (APC) and Dlg1-SAP97, are required for the polarization of migrating astrocytes. Activation of the Par6-PKCzeta complex by Cdc42 at the leading edge of migrating cells promotes both the localized association of APC with microtubule plus ends and the assembly of Dlg-containing puncta in the plasma membrane. Biochemical analysis and total internal reflection fluorescence microscopy reveal that the subsequent physical interaction between APC and Dlg1 is required for polarization of the microtubule cytoskeleton. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16157700&query_hl=1 ER - TY - JFULL T1 - Lateralisation of striatal function: evidence from 18F-dopa PET in Parkinson's disease. A1 - Cheesman, AL A1 - Barker, RA A1 - Lewis, SJ A1 - Robbins, TW A1 - Owen, AM A1 - Brooks, DJ J1 - J Neurol Neurosurg Psychiatry Y1 - 2005/09// VL - 76 SN - 0022-3050 SP - 1204 EP - 1210 N2 - OBJECTIVES: The aetiology of the cognitive changes seen in Parkinson's disease (PD) is multifactorial but it is likely that a significant contribution arises from the disruption of dopaminergic pathways. This study aimed to investigate the contribution of the dopaminergic system to performance on two executive tasks using (18)F-6-fluorodopa positron emission tomography ((18)F-dopa PET) in PD subjects with early cognitive changes. METHODS: 16 non-demented, non-depressed PD subjects were evaluated with the Tower of London (TOL) spatial planning task, a verbal working memory task (VWMT) and (18)F-dopa PET, all known to be affected in early PD. Statistical parametric mapping (SPM) localised brain regions in which (18)F-dopa uptake covaried with performance scores. Frontal cortical resting glucose metabolism was assessed with (18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG) PET. RESULTS: SPM localised significant covariation between right caudate (18)F-dopa uptake (Ki) and TOL scores and between left anterior putamen Ki and VWMT performance. No significant covariation was found between task scores and (18)F-dopa Ki values in either limbic or cortical regions. Frontal cortical glucose metabolism was preserved in all cases. CONCLUSIONS: These findings support a causative role of striatal dopaminergic depletion in the early impairment of executive functions seen in PD. They suggest that spatial and verbal executive tasks require integrity of the right and left striatum, respectively, and imply that the pattern of cognitive changes manifest by a patient with PD may reflect differential dopamine loss in the two striatal complexes. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16107352&query_hl=1 ER - TY - JFULL T1 - Maternal origin of inflammatory leukocytes in preterm fetal membranes, shown by fluorescence in situ hybridisation. A1 - Steel, JH A1 - O'donoghue, K A1 - Kennea, NL A1 - Sullivan, MH A1 - Edwards, AD J1 - Placenta Y1 - 2005/09// VL - 26 SN - 0143-4004 SP - 672 EP - 677 N2 - The aim of this study was to determine the maternal or fetal origin of inflammatory leukocytes in fetal membranes from cases of chorioamnionitis. Fetal membranes were collected from male preterm infants and chorioamnionitis was diagnosed histologically. Fluorescence in situ hybridisation for X and Y chromosomes was used to determine the gender of infiltrating leukocytes in the chorion and amnion. Leukocytes, trophoblast and mesenchymal cells were identified using immunohistochemistry for CD45, cytokeratin-7 and vimentin, respectively. Leukocytes present in the chorion and amnion were labelled XX, indicating maternal origin, and these cells were immunoreactive for the leukocyte marker CD45 but not for vimentin or cytokeratin-7. All other cells in the chorion and amnion were labelled XY and of fetal origin. The results indicated that maternal leukocytes invade the amnion and chorion in chorioamnionitis and we suggest that this is part of the maternal inflammatory response to intrauterine infection. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16085046&query_hl=1 ER - TY - JFULL T1 - Alteration of sympathetic function in hibernating myocardium A1 - John, AS A1 - Depre, C A1 - Rimoldi, OE A1 - Pepper, JR A1 - Vatner, DE A1 - Vatner, SF A1 - Pennell, DJ A1 - Camici, PG J1 - EUR HEART J Y1 - 2005/09// VL - 26 SN - 0195-668X SP - 222 EP - 222 ER - TY - JFULL T1 - Cardiovascular magnetic resonance in the quantitative assessment of left ventricular mass, volumes and contractile function. A1 - Lyne, JC A1 - Pennell, DJ J1 - Coron Artery Dis Y1 - 2005/09// VL - 16 SN - 0954-6928 SP - 337 EP - 343 N2 - Cardiovascular magnetic resonance is a well validated, highly accurate and reproducible technique for the assessment of ventricular volumes, function and mass. State of the art cardiovascular magnetic resonance practice is capable of a ventricular assessment that includes not only systolic but also diastolic function. Thus, it provides an insight into the complex changes in ventricular morphology, physiology and function in cardiovascular disease. This has produced great interest not only in its clinical utilization but also as an important research tool. As refinement of the technique continues to incorporate hardware and software developments, the technique becomes quicker, more accurate and easier to analyse. Here, we review recent developments and current practice. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16118538&query_hl=1 ER - TY - JFULL T1 - Evaluation of heart rate turbulence in adults with repaired tetralogy of Fallot A1 - Davos, C A1 - Alexandridi, A A1 - Petropoulou, E A1 - Varela, E A1 - Kilner, P A1 - Piepoli, M A1 - Gatzoulis, M A1 - Boudoulas, H J1 - EUR HEART J Y1 - 2005/09// VL - 26 SN - 0195-668X SP - 90 EP - 90 ER - TY - JFULL T1 - Cardiovascular magnetic resonance of anomalous coronary arteries. A1 - Varghese, A A1 - Keegan, J A1 - Pennell, DJ J1 - Coron Artery Dis Y1 - 2005/09// VL - 16 SN - 0954-6928 SP - 355 EP - 364 N2 - Cardiovascular magnetic resonance of anomalous coronary arteries is a class I indication. The term anomalous coronary artery encompasses those with an abnormal origin (from the incorrect sinus, too-high or too-low from the correct sinus, or from the pulmonary artery) and/or number of ostia. Their clinical significance results from the increased risk of myocardial infarction and sudden cardiac death associated with those traversing an interarterial course between the aorta and main pulmonary artery/right ventricular outflow tract. In this article, we review the role and practice of cardiovascular magnetic resonance in this field. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16118540&query_hl=1 ER - TY - JFULL T1 - Abnormal cortical excitability in sporadic but not homozygous D90A SOD1 ALS. A1 - Turner, MR A1 - Osei-Lah, AD A1 - Hammers, A A1 - Al-Chalabi, A A1 - Shaw, CE A1 - Andersen, PM A1 - Brooks, DJ A1 - Leigh, PN A1 - Mills, KR J1 - J Neurol Neurosurg Psychiatry Y1 - 2005/09// VL - 76 SN - 0022-3050 SP - 1279 EP - 1285 N2 - BACKGROUND: Excitotoxicity is one pathogenic mechanism proposed in amyotrophic lateral sclerosis (ALS), and loss of cortical inhibitory influence may be contributory. Patients with ALS who are homozygous for the D90A superoxide dismutase-1 (SOD1) gene mutation (homD90A) have a unique phenotype, associated with prolonged survival compared with patients with sporadic ALS (sALS). In this study, transcranial magnetic stimulation (TMS) was used to explore cortical excitation and inhibition. Flumazenil binds to the benzodiazepine subunit of the GABA(A) receptor, and (11)C-flumazenil positron emission tomography (PET) was used as a marker of cortical neuronal loss and/or dysfunction, which might in turn reflect changes in cortical inhibitory GABAergic mechanisms. METHODS: Cortical responses to single and paired stimulus TMS were compared in 28 patients with sALS and 11 homD90A patients versus 24 controls. TMS measures included resting motor threshold, central motor conduction time, silent period, intracortical inhibition (ICI), and facilitation. (11)C-flumazenil PET of the brain was performed on 20 patients with sALS and nine with homD90A. Statistical parametric mapping was used to directly compare PET images from the two patient groups to identify those areas of relatively reduced cortical (11)C-flumazenil binding that might explain differences in cortical excitability seen using TMS. RESULTS: Increased cortical excitability, demonstrated by reduction in ICI, was seen in the patients with sALS but not the homD90A patients. A relative reduction in cortical (11)C-flumazenil binding was found in the motor and motor association regions of the superior parietal cortices of the patients with sALS. CONCLUSIONS: A cortical inhibitory deficit in sALS was not demonstrable in a homogeneous genetic ALS population of similar disability, suggesting a distinct cortical vulnerability. (11)C-flumazenil PET demonstrated that neuronal loss/dysfunction in motor and motor association areas may underlie this difference. The corollary, that there may be relative preservation of neuronal function in these areas in the homD90A group, has implications for understanding the slower progression of disease in these patients. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16107368&query_hl=1 ER - TY - JFULL T1 - Pulmonary regurgitant fraction is lower by expiratory breath-hold velocity mapping than by inspiratory or non-breath-hold A1 - Johansson, B A1 - Babu-Narayan, SV A1 - Kilner, PJ J1 - EUR HEART J Y1 - 2005/09// VL - 26 SN - 0195-668X SP - 88 EP - 88 ER - TY - JFULL T1 - Images in cardiovascular medicine. Pericardiocentesis at 14 weeks: effective treatment of pericardial effusion complicating right ventricular diverticulum. A1 - Gardiner, HM A1 - Wimalasundera, R A1 - Pasquini, L A1 - Wawryk, S A1 - Ho, SY J1 - Circulation Y1 - 2005/08/30/ VL - 112 SN - 1524-4539 SP - e120 EP - e120 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16129806&query_hl=1 ER - TY - JFULL T1 - Muscle metabolites, detected in urine by proton spectroscopy, correlate with disease damage in juvenile idiopathic inflammatory myopathies. A1 - Chung, YL A1 - Rider, LG A1 - Bell, JD A1 - Summers, RM A1 - Zemel, LS A1 - Rennebohm, RM A1 - Passo, MH A1 - Hicks, J A1 - Miller, FW A1 - Scott, DL A1 - Juvenile Dermatomyositis Disease Activity Collaborative Study Group J1 - Arthritis Rheum Y1 - 2005/08/15/ VL - 53 SN - 0004-3591 SP - 565 EP - 570 N2 - OBJECTIVE: To assess for novel markers of muscle damage using urinary muscle metabolites by 1H magnetic resonance spectroscopy in patients with juvenile idiopathic inflammatory myopathy (IIM). METHODS: Creatine (Cr), choline (Cho), betaine (Bet), glycine (Gly), trimethylamine oxide (TMAO), and several other metabolites were measured in first morning void urine samples from 45 patients with juvenile IIM and from 35 healthy age-matched controls, and correlated with measures of myositis disease activity and damage. Urinary metabolite to age-adjusted creatinine (Cn) ratios were examined. RESULTS: Age-adjusted initial Cr:Cn, Cho:Cn, Bet:Cn, Gly:Cn, and TMAO:Cn ratios were higher in patients with juvenile IIM than controls (P < 0.01). Cr:Cn ratios showed significant correlations with physician-assessed global disease damage (Spearman rs = 0.37; P = 0.01), Steinbrocker functional class (rs = 0.35; P = 0.02), serum Cr (rs = 0.72; P = 0.001), and lactate dehydrogenase (rs = 0.34; P = 0.03) levels. Cho:Cn (rs = 0.3; P = 0.05), Gly:Cn (rs = 0.33; P = 0.03), and TMAO:Cn (rs = 0.36; P = 0.02) ratios showed a significant correlation with serum aldolase levels. Cho:Cn ratios also showed a significant correlation with aspartate aminotransferase levels (rs = 0.35; P = 0.02). A linear regression model was used to evaluate the factors influencing urinary Cr:Cn ratios in the 43 patients with data sets available at the initial visit. The regression model explained 73% of the variation in Cr:Cn ratios. The most significant factor was the physician-assessed global disease damage (R2 = 0.50, P = 0.015). CONCLUSION: Urinary Cr:Cn, Cho:Cn, Bet:Cn, Gly:Cn, and TMAO:Cn ratios are elevated in juvenile IIM and Cr:Cn correlates strongly with global disease damage. The Cr:Cn ratio may have potential utility as a marker of myositis disease damage. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16082628&query_hl=1 ER - TY - JFULL T1 - Non-invasive intrapartum fetal ECG: preliminary report. A1 - Taylor, MJ A1 - Thomas, MJ A1 - Smith, MJ A1 - Oseku-Afful, S A1 - Fisk, NM A1 - Green, AR A1 - Paterson-Brown, S A1 - Gardiner, HM J1 - BJOG Y1 - 2005/08// VL - 112 SN - 1470-0328 SP - 1016 EP - 1021 N2 - OBJECTIVES: To obtain fetal heart rate, detailed fetal electrocardiography (fECG) signals and uterine contractions during labour using a single device. DESIGN: Prospective observational study. SETTING: Delivery suite at a tertiary referral hospital, London, UK. POPULATION: Fifteen patients at median gestation of 39 weeks (range 24-41) were recruited at median cervical dilatation of 4.0 cm (range 0-10) of whom 8/15 (53%) had intact amniotic membranes. METHODS: Using 12 abdominally sited electrodes, we recorded the composite abdominal signal in pregnancies intrapartum. The recorded data were analysed off-line using a blind signal separation technique. MAIN OUTCOME MEASURES: Success of signal separation and fECG time intervals. RESULTS: Successful fECG signal acquisition was achieved in 12/15 (80%) patients and an averaged fECG waveform acquired. In these patients, P and QRS waves were seen in all cases, and T waves in 11/12 (92%). True beat-to-beat heart rate (HR) was displayed and measures of its variability obtained. The mother's ECG and uterine electrical activity, shown to match tocographically recorded uterine contractions, were also separated and displayed. Failure to acquire fECG in three cases was attributed to excessive abdominal muscular activity and electrical interference. CONCLUSIONS: This study demonstrates a non-invasive technique that displays detailed intrapartum fECG waveforms, HR variability, maternal ECG and uterine contractions simultaneously, all in a single device and which avoids the potential risks of invasive monitoring with a fetal scalp electrode. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16045511&query_hl=1 ER - TY - JFULL T1 - Xenon and hypothermia combine to provide neuroprotection from neonatal asphyxia. A1 - Ma, D A1 - Hossain, M A1 - Chow, A A1 - Arshad, M A1 - Battson, RM A1 - Sanders, RD A1 - Mehmet, H A1 - Edwards, AD A1 - Franks, NP A1 - Maze, M J1 - Ann Neurol Y1 - 2005/08// VL - 58 SN - 0364-5134 SP - 182 EP - 193 N2 - Perinatal asphyxia can result in neuronal injury with long-term neurological and behavioral consequences. Although hypothermia may provide some modest benefit, the intervention itself can produce adverse consequences. We have investigated whether xenon, an antagonist of the N-methyl-D-aspartate subtype of the glutamate receptor, can enhance the neuroprotection provided by mild hypothermia. Cultured neurons injured by oxygen-glucose deprivation were protected by combinations of interventions of xenon and hypothermia that, when administered alone, were not efficacious. A combination of xenon and hypothermia administered 4 hours after hypoxic-ischemic injury in neonatal rats provided synergistic neuroprotection assessed by morphological criteria, by hemispheric weight, and by functional neurological studies up to 30 days after the injury. The protective mechanism of the combination, in both in vitro and in vivo models, involved an antiapoptotic action. If applied to humans, these data suggest that low (subanesthetic) concentrations of xenon in combination with mild hypothermia may provide a safe and effective therapy for perinatal asphyxia. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16049939&query_hl=1 ER - TY - JFULL T1 - p53 Mutations in human cholangiocarcinoma: a review. A1 - Khan, SA A1 - Thomas, HC A1 - Toledano, MB A1 - Cox, IJ A1 - Taylor-Robinson, SD J1 - Liver Int Y1 - 2005/08// VL - 25 SN - 1478-3223 SP - 704 EP - 716 N2 - The reported mortality from intrahepatic bile duct tumours is increasing markedly in industrialised countries, for reasons that remain unknown. Inactivation of the tumour suppressor gene p53, is the commonest genetic abnormality in human cancer and has been implicated in the genesis of cholangiocarcinoma in various immunohistochemical and molecular epidemiological investigations, including gene sequencing studies. The structure and function of p53 and its role in linking cancer to specific carcinogens by way of mutational signatures is reviewed. The findings of previous p53 studies and their relevance in human cholangiocarcinoma are summarised. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15998419&query_hl=1 ER - TY - JFULL T1 - Diffusion tractography of the corticospinal tracts in the developing preterm brain A1 - Counsell, SJ A1 - Srinivasan, L A1 - Boardman, JP A1 - Larkman, DJ A1 - Allsop, JM A1 - Fitzpatrick, JA A1 - Cowan, FM A1 - Hajnal, JV A1 - Edwards, AD A1 - Rutherford, MA J1 - PEDIATR RES Y1 - 2005/08// VL - 58 SN - 0031-3998 SP - 366 EP - 366 ER - TY - JFULL T1 - Detection of vascular expression of E-selectin in vivo by MR imaging A1 - Reynolds, PR A1 - Larkman, DJ A1 - Haskard, DO A1 - Hajnal, JV A1 - Kennea, NL A1 - George, AJT A1 - Edwards, AD J1 - PEDIATR RES Y1 - 2005/08// VL - 58 SN - 0031-3998 SP - 407 EP - 407 ER - TY - JFULL T1 - Qualitative analysis of artefacts on raw EEG and the influence on aEEG classification A1 - Hagmann, CF A1 - Robertson, NJ A1 - Azzopardi, D J1 - PEDIATR RES Y1 - 2005/08// VL - 58 SN - 0031-3998 SP - 382 EP - 382 ER - TY - JFULL T1 - Total cerebral volume measurements following preterm birth A1 - Boardman, JP A1 - Counsell, S A1 - Vaid, I A1 - Hajnal, JV A1 - Rueckert, D A1 - Kapellou, O A1 - Bhatia, KK A1 - Allsop, J A1 - Rutherford, M A1 - Edwards, AD J1 - PEDIATR RES Y1 - 2005/08// VL - 58 SN - 0031-3998 SP - 361 EP - 361 ER - TY - JFULL T1 - Serial magnetic resonance imaging of the preterm brain: The natural history of early lesions, abnormalities at term age and relation to outcome A1 - Dyet, L A1 - Kennea, N A1 - Maalouf, E A1 - Counsell, S A1 - Allsop, J A1 - Laroche, S A1 - Edwards, B A1 - Harrison, M A1 - Duggan, P A1 - Ajaye-Obe, M A1 - Battin, M A1 - Herlihy, A A1 - Hajnal, J A1 - Edwards, F J1 - PEDIATR RES Y1 - 2005/08// VL - 58 SN - 0031-3998 SP - 372 EP - 372 ER - TY - JFULL T1 - Molecular and bioinformatic detection of bacterial infection in preterm delivery A1 - Tan, S A1 - Cahill, R A1 - Dougan, G A1 - O'Gaora, P A1 - Pickard, D A1 - Kennea, N A1 - Sullivan, M A1 - Feldman, R A1 - Edwards, AD J1 - PEDIATR RES Y1 - 2005/08// VL - 58 SN - 0031-3998 SP - 418 EP - 418 ER - TY - JFULL T1 - Diverse modes of axon elaboration in the developing neocortex. A1 - Portera-Cailliau, C A1 - Weimer, RM A1 - De Paola, V A1 - Caroni, P A1 - Svoboda, K J1 - PLoS Biol Y1 - 2005/08// VL - 3 SN - 1545-7885 SP - e272 EP - e272 N2 - The development of axonal arbors is a critical step in the establishment of precise neural circuits, but relatively little is known about the mechanisms of axonal elaboration in the neocortex. We used in vivo two-photon time-lapse microscopy to image axons in the neocortex of green fluorescent protein-transgenic mice over the first 3 wk of postnatal development. This period spans the elaboration of thalamocortical (TC) and Cajal-Retzius (CR) axons and cortical synaptogenesis. Layer 1 collaterals of TC and CR axons were imaged repeatedly over time scales ranging from minutes up to days, and their growth and pruning were analyzed. The structure and dynamics of TC and CR axons differed profoundly. Branches of TC axons terminated in small, bulbous growth cones, while CR axon branch tips had large growth cones with numerous long filopodia. TC axons grew rapidly in straight paths, with frequent interstitial branch additions, while CR axons grew more slowly along tortuous paths. For both types of axon, new branches appeared at interstitial sites along the axon shaft and did not involve growth cone splitting. Pruning occurred via retraction of small axon branches (tens of microns, at both CR and TC axons) or degeneration of large portions of the arbor (hundreds of microns, for TC axons only). The balance between growth and retraction favored overall growth, but only by a slight margin. Given the identical layer 1 territory upon which CR and TC axons grow, the differences in their structure and dynamics likely reflect distinct intrinsic growth programs for axons of long projection neurons versus local interneurons. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16026180&query_hl=1 ER - TY - JFULL T1 - Comparison of aEEG classification with the underlying single channel raw EEG background activity in neontal encephalopathy A1 - Hagmann, CF A1 - Robertson, NJ A1 - Azzopardi, D J1 - PEDIATR RES Y1 - 2005/08// VL - 58 SN - 0031-3998 SP - 382 EP - 382 ER - TY - JFULL T1 - Orbital and maxillofacial computer aided surgery: patient-specific finite element models to predict surgical outcomes. A1 - Luboz, V A1 - Chabanas, M A1 - Swider, P A1 - Payan, Y J1 - Comput Methods Biomech Biomed Engin Y1 - 2005/08// VL - 8 SN - 1025-5842 SP - 259 EP - 265 N2 - This paper addresses an important issue raised for the clinical relevance of Computer-Assisted Surgical applications, namely the methodology used to automatically build patient-specific finite element (FE) models of anatomical structures. From this perspective, a method is proposed, based on a technique called the mesh-matching method, followed by a process that corrects mesh irregularities. The mesh-matching algorithm generates patient-specific volume meshes from an existing generic model. The mesh regularization process is based on the Jacobian matrix transform related to the FE reference element and the current element.This method for generating patient-specific FE models is first applied to computer-assisted maxillofacial surgery, and more precisely, to the FE elastic modelling of patient facial soft tissues. For each patient, the planned bone osteotomies (mandible, maxilla, chin) are used as boundary conditions to deform the FE face model, in order to predict the aesthetic outcome of the surgery. Seven FE patient-specific models were successfully generated by our method. For one patient, the prediction of the FE model is qualitatively compared with the patient's post-operative appearance, measured from a computer tomography scan. Then, our methodology is applied to computer-assisted orbital surgery. It is, therefore, evaluated for the generation of 11 patient-specific FE poroelastic models of the orbital soft tissues. These models are used to predict the consequences of the surgical decompression of the orbit. More precisely, an average law is extrapolated from the simulations carried out for each patient model. This law links the size of the osteotomy (i.e. the surgical gesture) and the backward displacement of the eyeball (the consequence of the surgical gesture). L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16298848&query_hl=1 ER - TY - JFULL T1 - Hypothermia and amiloride preserve energetics in a neonatal brain slice model. A1 - Robertson, NJ A1 - Bhakoo, K A1 - Puri, BK A1 - Edwards, AD A1 - Cox, IJ J1 - Pediatr Res Y1 - 2005/08// VL - 58 SN - 0031-3998 SP - 288 EP - 296 N2 - A period of secondary energy failure consisting of a decline in phosphocreatine/inorganic phosphate (PCr/Pi), a rise in brain lactate, and alkaline intracellular pH (pH(i)) has been described in infants with neonatal encephalopathy. Strategies that ameliorate this energy failure may be neuroprotective. We hypothesized that a neonatal rat brain slice model undergoes a progressive decline in energetics, which can be ameliorated with hypothermia or amiloride. Interleaved phosphorus ((31)P) and proton ((1)H) magnetic resonance (MR) spectra were obtained from 350 microm neonatal rat brain slices over 8 h in a bicarbonate buffer at 37 degrees C and at 32 degrees C in 7- and 14-d models. (31)P MR spectra were obtained with amiloride in a bicarbonate-free buffer at 37 degrees C in the 14-d model. Findings were similar in 7- and 14-d models. In the 14-d model, there was a Pi doublet structure corresponding to alkaline pH(i) values of 7.50 +/- 0.02 and 7.21 +/- 0.04. Compared with the stabilized baseline of 100, at 5 h PCr/Pi was 65 +/- 6.3 and lactate/NAA was 187 +/- 3 at 37 degrees C, but PCr/Pi and lactate/NAA were not significantly different from baseline at 32 degrees C. Nucleotide triphosphate (NTP)/phosphomonoester (PME) was 0.93 +/- 0.23 at 37 degrees C and 1.81 +/- 0.21 at 32 degrees C at 5 h. With amiloride exposure in the 14-d model, baseline pH(i) values were 7.25 +/- 0.09 and 6.98 +/- 0.02 and NTP/PME was 1.81 +/- 0.05; these parameters were not significantly different at 5 h. Our interpretation of these findings is that the brain slice model underwent secondary energy failure, which was delayed with hypothermia or amiloride. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16006423&query_hl=1 ER - TY - JFULL T1 - Cortical growth and neurocognitive impairment in preterm infants A1 - Kapellou, O A1 - Counsell, SJ A1 - Stark, J A1 - Maalouf, E A1 - Duggan, P A1 - Ajaye-Obe, M A1 - Dyet, L A1 - Hajnal, J A1 - Allsop, JM A1 - Rutherford, MA A1 - Cowan, F A1 - Edwards, AD J1 - PEDIATR RES Y1 - 2005/08// VL - 58 SN - 0031-3998 SP - 372 EP - 372 ER - TY - JFULL T1 - Visual findings in infants with periventricular leukomalacia A1 - Gallini, F A1 - Ricci, D A1 - Luciano, R A1 - Romagnoli, C A1 - Pane, M A1 - Donvito, V A1 - Baranello, G A1 - Rutherford, M A1 - Cowan, F A1 - Mercuri, E J1 - PEDIATR RES Y1 - 2005/08// VL - 58 SN - 0031-3998 SP - 378 EP - 378 ER - TY - JFULL T1 - White matter abnormality is associated with volume reduction in deep grey nuclei following preterm birth A1 - Boardman, JP A1 - Counsell, S A1 - Kapellou, O A1 - Rueckert, D A1 - Hajnal, JV A1 - Bhatia, KK A1 - Aljabar, P A1 - Rutherford, M A1 - Allsop, J A1 - Edwards, AD J1 - PEDIATR RES Y1 - 2005/08// VL - 58 SN - 0031-3998 SP - 362 EP - 362 ER - TY - JFULL T1 - Myocardial late gadolinium enhancement cardiovascular magnetic resonance in hypertrophic cardiomyopathy caused by mutations in troponin I. A1 - Moon, JC A1 - Mogensen, J A1 - Elliott, PM A1 - Smith, GC A1 - Elkington, AG A1 - Prasad, SK A1 - Pennell, DJ A1 - McKenna, WJ J1 - Heart Y1 - 2005/08// VL - 91 SN - 1468-201X SP - 1036 EP - 1040 N2 - OBJECTIVE: To examine the influence of genotype on late gadolinium enhancement (LGE) and the potential of cardiovascular magnetic resonance (CMR) to detect preclinical hypertrophic cardiomyopathy. DESIGN: Prospective, blinded cohort study of myocardial LGE in a genetically homogeneous population. PATIENTS: 30 patients with disease causing mutations in the recognised hypertrophic cardiomyopathy gene for cardiac troponin I (TNNI3): 15 with echocardiographically determined left ventricular hypertrophy (LVH+) and 15 without (LVH-). MAIN OUTCOME MEASURES: CMR measures of regional left ventricular function, wall thickness, and mass, and the extent and distribution of LGE. RESULTS: LGE was found in 12 (80%) LVH+ patients but with variable extent (mean 15%, range 3-48%). LGE was also found in two (13%) LVH- patients but the extent was limited (3.6%) and both patients were found to have an abnormal ECG and regional hypertrophy by cine CMR. The extent of LGE was positively associated with clinical markers of sudden death risk (21% with > or = 2 risk factors v 7% with < or = 1 risk factor, p = 0.02) and left ventricular mass (r = 0.56, p < 0.001) and was inversely associated with ejection fraction (r = -0.58, p < 0.001). Segmental analysis showed that as regional wall thickness increased, LGE was more prevalent (p < 0.0001) and more extensive (r = 0.98, p = 0.001). CONCLUSION: In patients with disease causing mutations in TNNI3, focal fibrosis was not detected by LGE CMR before LVH and ECG abnormalities were present. Once LVH is present, LGE is common and the extent correlates with adverse clinical parameters. This suggests that focal fibrosis is closely linked to disease development. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16020591&query_hl=1 ER - TY - JFULL T1 - GABA-benzodiazepine receptor function in alcohol dependence: a combined C-11-flumazenil PET and pharmacodynamic study A1 - Lingford-Hughes, AR A1 - Wilson, SJ A1 - Cunningham, VJ A1 - Feeney, A A1 - Stevenson, B A1 - Brooks, DJ A1 - Nutt, DJ J1 - PSYCHOPHARMACOLOGY Y1 - 2005/08// VL - 180 SN - 0033-3158 SP - 595 EP - 606 N2 - Rationale: Gamma-aminobutyric acid (GABA)benzodiazepine receptor function is hypothesised to be reduced in alcohol dependence. Objectives: We used positron emission tomography (PET) with [C-11]flumazenil, a non-selective tracer for brain GABA-benzodiazepine (GABA-BDZ) receptor binding, to determine in vivo the relationship between BDZ receptor occupancy by an agonist, midazolam, and its functional effects. Methods: Abstinent male alcohol dependent subjects underwent [C-11] flumazenil PET to measure occupancy of BDZ receptors by midazolam whilst recording its pharmacodynamic effects on behavioural and physiological measures. Rate constants describing the exchange of [C-11]flumazenil between the plasma and brain compartments were derived from time activity curves. Results: A 50% reduction in electro- encephalography (EEG)-measured sleep time was seen in the alcohol dependent group despite the same degree of occupancy by midazolam as seen in the control group. The effects of midazolam on other measures of benzodiazepine receptor function, increasing EEG betal power and slowing of saccadic eye movements, were similar in the two groups. No differences in midazolam or flumazenil metabolism were found between the groups. Conclusions: In summary, our study suggests that alcohol dependence in man is associated with a reduced EEG sleep response to the benzodiazepine agonist, midazolam, which is not explained by reduced BDZ receptor occupancy, and is consistent with reduced sensitivity in this measure of GABA-BDZ receptor function in alcohol dependence. The lack of change in other functional measures may reflect a differential involvement of particular subtypes of the GABA-BDZ receptor. ER - TY - JFULL T1 - Left ventricular diastolic function compared with T2* cardiovascular magnetic resonance for early detection of myocardial iron overload in thalassemia major. A1 - Westwood, MA A1 - Wonke, B A1 - Maceira, AM A1 - Prescott, E A1 - Walker, JM A1 - Porter, JB A1 - Pennell, DJ J1 - J Magn Reson Imaging Y1 - 2005/08// VL - 22 SN - 1053-1807 SP - 229 EP - 233 N2 - PURPOSE: To compare left ventricular (LV) diastolic function with myocardial iron levels in beta thalassemia major (TM) patients, using cardiovascular magnetic resonance (CMR). MATERIALS AND METHODS: We studied 67 regularly transfused patients with TM and 22 controls matched for age, gender, and body surface area. The early peak filling rate (EPFR) and atrial peak filling rate (APFR) were determined from high-temporal-resolution ventricular volume-time curves. Myocardial iron estimation was achieved using myocardial T2* measurements. RESULTS: Myocardial iron loading was found in 46 TM patients (69%), in whom the EPFR correlated poorly with T2* (r = -0.20, P = 0.19). The APFR (r = 0.49, P < 0.001) and EPFR/APFR ratio (r = -0.62, P < 0.001) correlated better with T2*. The sensitivity of the diastolic parameters for detecting myocardial iron loading ranged from 4% (EPFR and APFR) to 17% (EPFR/APFR ratio). CONCLUSION: Myocardial iron overload results in diastolic myocardial dysfunction, but low sensitivity limits the use of a single estimation for early detection of iron overload, for which T2* has a superior categorical limit of normality. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16028255&query_hl=1 ER - TY - JFULL T1 - Image-guided navigation in oral and maxillofacial surgery. A1 - Nijmeh, AD A1 - Goodger, NM A1 - Hawkes, D A1 - Edwards, PJ A1 - McGurk, M J1 - Br J Oral Maxillofac Surg Y1 - 2005/08// VL - 43 SN - 0266-4356 SP - 294 EP - 302 N2 - Image-guided surgery is the logical extension of imaging as it integrates previously acquired radiological or nuclear medicine images with the operative field. In conventional image-guided surgery, a surgeon uses a surgical instrument or a pointer to establish correspondence between features in the preoperative images and the surgical scene. This is not ideal because the surgeon has to look away from the operative field to view the data. Augmented reality guidance systems offer a solution to this problem but are limited by deformation of soft tissues. Real-time intraoperative imaging offers a potential solution but is currently only experimental. The additional precision and confidence that this technology provides make it a useful tool, and recent advances in image-guided surgery offer new opportunities in the field of oral and maxillofacial surgery. Here, we review the development, current technologies, and applications of image-guided surgery and illustrate them with two case reports. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15993282&query_hl=1 ER - TY - JFULL T1 - Prolapse of the antero-superior leaflet of the tricuspid valve secondary to congenital anomalies of the valvar and sub-valvar apparatus: a rare cause of severe tricuspid regurgitation. A1 - Abrams, DJ A1 - Kilner, P A1 - Till, JA A1 - Shore, DF A1 - Sethia, B A1 - Franklin, RC A1 - Magee, AG J1 - Cardiol Young Y1 - 2005/08// VL - 15 SN - 1047-9511 SP - 417 EP - 421 N2 - Congenital anomalies of the tricuspid valve, and/or its supporting apparatus, leading to severe tricuspid regurgitation are rare. Although well tolerated in early childhood, long-standing and progressive volume loading of the right heart leads to symptoms of decreased exercise tolerance, and may predispose to arrhythmias in the long term. We report three cases of severe tricuspid regurgitation related to anomalies of the cords supporting the antero-superior leaflet of the tricuspid valve. Shortened cords leading to tethering of the leaflet were seen in two cases, and hypoplasia of the leaflet in the other. In all cases, the regurgitant jet was directed posteriorly towards the coronary sinus and atrial septum. Surgical repair was possible in one case, while it proved necessary to replace the valve in a second. The third child is asymptomatic and under regular review. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16014191&query_hl=1 ER - TY - JFULL T1 - Surrogate markers for atherosclerotic disease. A1 - Sankatsing, RR A1 - de Groot, E A1 - Jukema, JW A1 - de Feyter, PJ A1 - Pennell, DJ A1 - Schoenhagen, P A1 - Nissen, SE A1 - Stroes, ES A1 - Kastelein, JJ J1 - Curr Opin Lipidol Y1 - 2005/08// VL - 16 SN - 0957-9672 SP - 434 EP - 441 N2 - PURPOSE OF REVIEW: Novel treatment modalities for cardiovascular prevention are emerging rapidly. Since it is virtually impossible to evaluate all these new compounds in long-term trials using clinical end points, there is an urgent need for validated surrogate markers of atherosclerosis to save both time and costs. Over the last decade, the use of imaging markers has been widely introduced into drug-development strategies. Here we will discuss the most commonly used techniques. RECENT FINDINGS: Whereas both testing of endothelial function, assessed as flow-mediated dilation, and assessment of carotid intima-media thickness have been shown to predict future cardiovascular events, predominantly intima-media thickness has been used successfully as a surrogate marker in intervention studies. More recently, standardization of intravascular ultrasound has also enabled reproducible assessment of coronary atheroma volume. Multidetector computed tomography and electron-beam computed tomography have proven useful in providing quantitative information on plaque burden and coronary calcium content, respectively. Although cardiovascular magnetic resonance (CMR) is improving continuously, additional technical improvements will be mandatory before this technique can be implemented in multicenter clinical studies. SUMMARY: The imaging modalities reviewed here all provide specific information on either functionality or morphology of the vasculature. The value of carotid intima-media thickness for cardiovascular risk prediction has been studied most extensively. Whereas assessment of plaque burden using intravascular ultrasound appears to be the most direct way to quantify coronary changes, its predictive value for future cardiovascular events remains to be established. Awaiting further technical improvements, CMR is expected to provide the most valuable information for the evaluation of atherosclerosis in the near future. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15990593&query_hl=1 ER - TY - JFULL T1 - Proton and phosphorus-31 nuclear magnetic resonance spectroscopy of human bile in hepatopancreaticobiliary cancer. A1 - Khan, SA A1 - Cox, IJ A1 - Thillainayagam, AV A1 - Bansi, DS A1 - Thomas, HC A1 - Taylor-Robinson, SD J1 - Eur J Gastroenterol Hepatol Y1 - 2005/07// VL - 17 SN - 0954-691X SP - 733 EP - 738 N2 - OBJECTIVE: Hepatopancreaticobiliary cancers can be difficult to diagnose. Nuclear magnetic resonance (NMR) spectroscopy provides non-invasive information on phospholipid metabolism, and previous studies of liver tissue have highlighted changes in phospholipids in malignancy. We hypothesised that in-vitro NMR spectroscopy of human bile may provide independent diagnostic indices in cancer management through an assessment of the phospholipid content. DESIGN AND METHODS: Bile samples from 24 patients were collected at endoscopic retrograde cholangiopancreatography and from one subject at cholecystectomy. Thirteen patients had cancer: pancreatic carcinoma (eight), cholangiocarcinoma (three) and metastatic liver disease (two). The remaining 12 patients had non-malignant pathology. In-vitro proton (H) and phosphorus-31 (P) NMR spectra were obtained from all samples using an 11.7 Tesla NMR spectroscopy system. RESULTS: Complementary information was obtained from the H and P NMR spectra. Signals were assigned to phosphatidylcholine in both H and P NMR spectra. Phosphatidylcholine levels were significantly reduced in the bile from cancer patients when compared with bile from non-cancer patients (P=0.007). CONCLUSION: These preliminary studies suggest that H and P NMR spectroscopy of bile may be used to detect differences in phospholipid content between cancer and non-cancer patients. This may have implications for the development of novel diagnostic strategies in hepatopancreaticobiliary cancers. Further larger-scale studies are warranted. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15947550&query_hl=1 ER - TY - JFULL T1 - Tolerant T cells display impaired trafficking ability. A1 - Mirenda, V A1 - Millington, O A1 - Lechler, RI A1 - Scott, D A1 - Hernandez-Fuentes, MP A1 - Read, J A1 - Tan, PH A1 - George, AJ A1 - Garside, P A1 - Marelli-Berg, FM J1 - Eur J Immunol Y1 - 2005/07// VL - 35 SN - 0014-2980 SP - 2146 EP - 2156 N2 - Based on our previous observation that anergic T lymphocytes lose their migratory ability in vitro, we have proposed that anergic T cells are retained in the site where they have been generated to exert their regulatory function. In this study we have analyzed T lymphocyte trafficking and motility following the induction of tolerance in vivo. In a model of non-deletional negative vaccination to xenoantigens in which dendritic cells (DC) localize to specific lymphoid sites depending on the route of administration, tolerant T cells remained localized in the lymph nodes colonized by tolerogenic DC, while primed T cells could traffic efficiently. Using an oral tolerance model that enables the 'tracking' of ovalbumin-specific TCR-transgenic T cells, we confirmed that T cells lose the ability to migrate through syngeneic endothelial cell monolayers following tolerance induction in vivo. Finally, we show that tolerant T cells (both in vitro and ex vivo) can inhibit migration of responsive T cells in an antigen-independent manner. Thus, hyporesponsive T cells localize at the site of tolerance induction in vivo, where they exert their anti-inflammatory properties. In physiological terms, this effect is likely to render immunoregulation a more efficient and controllable event. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15948215&query_hl=1 ER - TY - JFULL T1 - Response of the fetal heart to changes in load: from hyperplasia to heart failure. A1 - Gardiner, HM J1 - Heart Y1 - 2005/07// VL - 91 SN - 1468-201X SP - 871 EP - 873 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15958350&query_hl=1 ER - TY - JFULL T1 - Generic method for imaging transgene expression. A1 - So, PW A1 - Hotee, S A1 - Herlihy, AH A1 - Bell, JD J1 - Magn Reson Med Y1 - 2005/07// VL - 54 SN - 0740-3194 SP - 218 EP - 221 N2 - We propose a generic method to report on gene expression based on the use of an antigen-antibody reporting system and visualization by MRI. This methodology was demonstrated using a truncated form of the H2K(k) antigen, tH2K(k), as the nonendogenous antigen to be imaged. HeLa cells, transfected to express tH2K(k), exposed to tH2K(k) antibodies conjugated to a superparamagnetic iron oxide particle, generated strong negative contrast compared to non-H2K(k) expressing cells by MRI. T(2) of the tH2K(k) expressing cells was 57.6 +/- 17.0 ms, compared to 424.0 +/- 38.7 and 445.4 +/- 47.2 ms for the mock transfected and nontransfected cells, respectively (P < 0.001). tH2K(k) expression in the former cells was confirmed by flow cytometry, fluorescence, and electron microscopy. The methodology can be adapted to image in vivo other nonendogenous antigens in cells/tissues. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15968675&query_hl=1 ER - TY - JFULL T1 - Cystic duct dilatation after cholecystectomy in fibropolycystic liver disease. A1 - Dhanjal, NS A1 - Sharif, AW A1 - Rosenfelder, NA A1 - Lim, AK A1 - Taylor-Robinson, SD J1 - J Hepatol Y1 - 2005/07// VL - 43 SN - 0168-8278 SP - 192 EP - 192 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15953508&query_hl=1 ER - TY - JFULL T1 - Glial cell line-derived neurotrophic factor induces neuronal sprouting in human brain A1 - Love, S A1 - Plaha, P A1 - Patel, NK A1 - Hotton, GR A1 - Brooks, DJ A1 - Gill, SS J1 - NAT MED Y1 - 2005/07// VL - 11 SN - 1078-8956 SP - 703 EP - 704 ER - TY - JFULL T1 - Inhibition of NF-kappa B and oxidative pathways in human dendritic cells by antioxidative vitamins generates regulatory T cells. A1 - Tan, PH A1 - Sagoo, P A1 - Chan, C A1 - Yates, JB A1 - Campbell, J A1 - Beutelspacher, SC A1 - Foxwell, BM A1 - Lombardi, G A1 - George, AJ J1 - J Immunol Y1 - 2005/06/15/ VL - 174 SN - 0022-1767 SP - 7633 EP - 7644 N2 - Dendritic cells (DCs) are central to T cell immunity, and many strategies have been used to manipulate DCs to modify immune responses. We investigated the effects of antioxidants ascorbate (vitamin C) and alpha-tocopherol (vitamin E) on DC phenotype and function. Vitamins C and E are both antioxidants, and concurrent use results in a nonadditive activity. We have demonstrated that DC treated with these antioxidants are resistant to phenotypic and functional changes following stimulation with proinflammatory cytokines. Following treatment, the levels of intracellular oxygen radical species were reduced, and the protein kinase RNA-regulated, eukaryotic translation initiation factor 2alpha, NF-kappaB, protein kinase C, and p38 MAPK pathways could not be activated following inflammatory agent stimulation. We went on to show that allogeneic T cells (including CD4(+)CD45RO, CD4(+)CD45RA, and CD4(+)CD25(-) subsets) were anergized following exposure to vitamin-treated DCs, and secreted higher levels of Th2 cytokines and IL-10 than cells incubated with control DCs. These anergic T cells act as regulatory T cells in a contact-dependent manner that is not dependent on IL-4, IL-5, IL-10, IL-13, and TGF-beta. These data indicate that vitamin C- and E-treated DC might be useful for the induction of tolerance to allo- or autoantigens. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15944264&query_hl=1 ER - TY - JFULL T1 - Distinct cerebral lesions in sporadic and 'D90A' SOD1 ALS: studies with [11C]flumazenil PET. A1 - Turner, MR A1 - Hammers, A A1 - Al-Chalabi, A A1 - Shaw, CE A1 - Andersen, PM A1 - Brooks, DJ A1 - Leigh, PN J1 - Brain Y1 - 2005/06// VL - 128 SN - 1460-2156 SP - 1323 EP - 1329 N2 - Five to ten percent of amyotrophic lateral sclerosis (ALS) cases are associated with mutations of the superoxide dismutase-1 (SOD1) gene, and the 'D90A' mutation is associated with a unique phenotype and markedly slower disease progression (mean survival time 14 years). Relative sparing of inhibitory cortical neuronal circuits might be one mechanism contributing to the slower progression in patients homozygous for the D90A mutation (homD90A). The GABA(A) receptor PET ligand [11C]flumazenil has demonstrated motor and extra-motor cortical changes in sporadic ALS. In this study, we used [11C]flumazenil PET to explore differences in the pattern of cortical involvement between sporadic and genetically homogeneous ALS groups. Twenty-four sporadic ALS (sALS) and 10 homD90A patients underwent [11C]flumazenil PET of the brain. In addition, two subjects homozygous for the D90A mutation, but without symptoms or signs ('pre-symptomatic', psD90A), also underwent imaging. Results for each group were compared with those for 24 healthy controls of similar age. Decreases in the binding of [11C]flumazenil in the sALS group were found within premotor regions, motor cortex and posterior motor association areas. In the homD90A group of ALS patients, however, decreases were concentrated in the left fronto-temporal junction and anterior cingulate gyrus. In the two psD90A subjects, a small focus of reduced [11C]flumazenil binding at the left fronto-temporal junction was seen, similar to the pattern seen in the clinically affected patients. Within the sALS group, there was no statistically significant association between decreases in cortical [11C]flumazenil binding and revised ALS functional rating scale (ALSFRS-R score), whereas the upper motor neuron (UMN) score correlated with widespread and marked cortical decreases over the dominant hemisphere. In the homD90A group, there was a stronger statistical association between reduced cortical [11C]flumazenil bindin